WO2013106072A1

WO2013106072A1 - Compositions comprising crosslinked cation-binding polymers and uses thereof

Info

Publication number: WO2013106072A1
Application number: PCT/US2012/038908
Authority: WO
Inventors: Alan D. Strickland; George M. Grass
Original assignee: Sorbent Therapeutics, Inc.
Priority date: 2012-01-10
Filing date: 2012-05-21
Publication date: 2013-07-18
Also published as: CA2863240A1; IL233578A0

Abstract

The present disclosure relates generally to crosslinked cation-binding polymers comprising monomers containing carboxylic acid groups, wherein the polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% or about 15% to about 35% of the carboxylic acid groups in the polymer. The present disclosure also relates to methods of preparation of the polymers, and compositions, formulations, and dosage forms containing the polymers, and methods of using the polymers, compositions, formulations, and/or dosage forms to treat various diseases or disorders.

Description

COMPOSITIONS COMPRISING CROSSLINKED CATION-BINDING

POLYMERS AND USES THEREOF

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of International Patent Application No. PCT/US 12/20849, filed on January 10, 2012, which is herein incorporated by reference herein in its entirety.

FIELD OF THE DISCLOSURE

[0002] The present disclosure relates generally to crosslinked cation-binding polymers comprising monomers comprising carboxylate groups and calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% or about 15% to about 35% of the carboxylate groups in the polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups in the polymer. The present disclosure also relates to methods of preparation of the polymers or compositions, formulations, and/or dosage forms containing the polymers, and methods of using the polymers or compositions, formulations, and/or dosage forms containing the polymers to treat various diseases or disorders.

BACKGROUND

[0003] Numerous diseases and disorders are associated with ion imbalances (e.g., hyperkalemia, hypernatremia, hypercalcemia, and hypermagnesia) and/or increased retention of fluid (e.g., heart failure and end stage renal disease (ESRD)). For example, patients afflicted with an increased level of potassium (e.g. , hyperkalemia) may exhibit a variety of symptoms ranging from malaise, palpitations, muscle weakness and, in severe cases, cardiac arrhythmias. Patients afflicted with increased levels of sodium (e.g., hypernatremia) may exhibit a variety of symptoms including, lethargy, weakness, irritability, edema and in severe cases, seizures and coma. Patients afflicted with retention of fluid often suffer from edema (e.g., pulmonary edema, peripheral edema, edema of the legs, etc.) and the buildup of waste products in the blood (e.g., urea, creatinine, other nitrogenous waste products, and electrolytes or minerals such as sodium, phosphate and potassium). [0004] Treatments for diseases or disorders associated with ion imbalances and/or an increased retention of fluid attempt to restore the ion balance and decrease the retention of fluid. For example, treatment of diseases or disorders associated with ion imbalances may employ the use of ion exchange resins to restore ion balance. Treatment of diseases or disorders associated with an increased retention of fluid may involve the use of diuretics (e.g., administration of diuretic agents and/or dialysis, such as hemodialysis or peritoneal dialysis and remediation of waste products that accumulate in the body). Additionally or alternatively, treatment for ion imbalances and/or increased retention of fluid may include restrictions on dietary consumption of electrolytes and water. However, the effectiveness and/or patient compliance with present treatments is less than desired.

BRIEF SUMMARY OF THE DISCLOSURE

[0005] The present disclosure is directed to compositions comprising crosslinked cation- binding polymers comprising monomers containing carboxylic acid groups.

[0006] The present disclosure relates generally to crosslinked cation-binding polymers comprising monomers containing carboxyate groups, wherein the polymers further comprise calcium and/or magnesium cations (e.g., calcium cations or magnesium cations or a mixture thereof), wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer (alternatively, the polymers comprise calcium and/or magnesium cations that are counterions to about 5% to about 10%, about 5%) to about 15%, about 5% to about 20%>, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30%, for example, about 25%, of the carboxylate groups in the polymer), and wherein sodium cations are counterions to no more than about 5% (alternatively, no more than about 4%, about 3%, about 2%), or about 1%, about 0.5%, about 0.05%, or about 0.01%) of the carboxylate groups on the polymer.

[0007] The present disclosure also relates generally to crosslinked cation-binding polymers comprising monomers containing carboxyate groups, wherein the polymers further comprise calcium and/or magnesium cations (e.g., calcium cations or magnesium cations or a mixture thereof), wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, the polymers comprise calcium and/or magnesium cations that are counterions to about about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20%) to about 35%), about 25% to about 30%, or about 25% to about 35%, for example, about 25%), of the carboxylate groups in the polymer), and wherein sodium cations are counterions to no more than about 5% (alternatively, no more than about 4%, about 3%, about 2%), or about 1%, about 0.5%, about 0.05%, or about 0.01%) of the carboxylate groups on the polymer.

[0008] In some embodiments, at least a portion of the polymer is derived from acrylic acid monomers or acrylic acid derivative monomers. In some embodiments, all or substantially all of the polymer is derived from acrylic acid monomers or acrylic acid derivative monomers. In some embodiments, the polymer is crosslinked polyacrylate. In some embodiments, the polymer comprises calcium cations. The present disclosure also relates to methods of preparation of crosslinked cation-binding polymers comprising monomers that comprise carboxylate groups, for example, crosslinked polyacrylic acid, wherein the polymers further comprise calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer (alternatively, the polymers comprise calcium and/or magnesium cations that are counterions to about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%), about 20% to about 30%, or about 25% to about 30%, for example, about 25%, of the carboxylate groups in the polymer), and wherein the polymers may comprise sodium cations that are counterions to no more than about 5% (alternatively, no more than about 4%, about 3%, about 2%, or about 1%, about 0.5%, about 0.1%, or about 0.05%) of the carboxylate groups in the polymer. Any suitable carboxylic acid-containing monomer known in the art may be used to prepare the compositions as disclosed herein, such as acrylic acid or a derivative thereof. Acrylic acid is a preferred monomer.

[0009] In some embodiments, at least a portion of the polymer is derived from acrylic acid monomers or acrylic acid derivative monomers. In some embodiments, all or substantially all of the polymer is derived from acrylic acid monomers or acrylic acid derivative monomers. In some embodiments, the polymer is crosslinked polyacrylate. In some embodiments, the polymer comprises calcium cations. The present disclosure also relates to methods of preparation of crosslinked cation-binding polymers comprising monomers that comprise carboxylate groups, for example, crosslinked polyacrylic acid, wherein the polymers further comprise calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, the polymers comprise calcium and/or magnesium cations that are counterions to about about 15% to about 20%, about 15% to about 25%, about 15% to about 30%>, about 15% to about 35%, about 20% to about 25%, about 20%) to about 30%, about 20% to about 35%, about 25% to about 30%, or about 25% to about 35%), for example, about 25%, of the carboxylate groups in the polymer), and wherein the polymers may comprise sodium cations that are counterions to no more than about 5% (alternatively, no more than about 4%, about 3%, about 2%, or about 1%, about 0.5%), about 0.1%), or about 0.05%) of the carboxylate groups in the polymer. Any suitable carboxylic acid-containing monomer known in the art may be used to prepare the compositions as disclosed herein, such as acrylic acid or a derivative thereof. Acrylic acid is a preferred monomer.

[0010] The present disclosure also relates to compositions, formulations, and/or dosage forms comprising crosslinked cation-binding polymers comprising monomers that comprise carboxylate groups, for example, crosslinked polyacrylic acid, wherein the polymers further comprise calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer (alternatively, the polymers comprise calcium and/or magnesium cations that are counterions to about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5%) to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%), or about 25% to about 30%, for example, about 25%, of the carboxylate groups in the polymer), and wherein the polymer may optionally comprise sodium cations that are counterions to less than about 5%, less than about 4%, less than about 3%, less than about 2%), or less than about 1% of the carboxylate groups. In some embodiments, compositions, formulations, and/or dosage forms according to the present disclosure may optionally further comprise an added base (for example, calcium carbonate) wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base. In alternate embodiments, composition, formulations, and/or dosage forms according to the present disclosure do not comprise an added base.

[0011] The present disclosure also relates to compositions, formulations, and/or dosage forms comprising crosslinked cation-binding polymers comprising monomers that comprise carboxylate groups, for example, crosslinked polyacrylic acid, wherein the polymers further comprise calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, the polymers comprise calcium and/or magnesium cations that are counterions to about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%), about 25% to about 30%, or about 25% to about 35%, for example, about 25%, of the carboxylate groups in the polymer), and wherein the polymer may optionally comprise sodium cations that are counterions to less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% of the carboxylate groups. In some embodiments, compositions, formulations, and/or dosage forms according to the present disclosure may optionally further comprise an added base (for example, calcium carbonate). The optionally added base may be included in an amount to provide up to about 0.8 equivalents of base per equivalent of carboxylate groups in the polymer. In alternate embodiments, composition, formulations, and/or dosage forms according to the present disclosure do not comprise an added base.

[0012] Any suitable base or combination of two or more bases may be used to prepare compositions as disclosed herein that contain a disclosed polymer and an optionally added base. In some embodiments, the composition comprises a base such as an alkali earth metal carbonate, an alkali earth metal acetate, an alkali earth metal oxide, an alkali earth metal bicarbonate, an alkali earth metal hydroxide, an organic base, or combinations thereof. In some embodiments, the base is a calcium base such as calcium carbonate, calcium acetate, calcium oxide, or combinations thereof. In some embodiments, the base is a magnesium base such as magnesium oxide. In some embodiments, the base is an organic base such as lysine, choline, histidine, arginine, or combinations thereof.

[0013] The present disclosure also relates to methods of preparation of the polymers and compositions, formulations, and/or dosage forms containing the polymers.

[0014] The present disclosure also relates to dosage forms (e.g., oral dosage forms) comprising one or more of the polymers, compositions and/or formulations disclosed herein.

[0015] The present disclosure also relates to methods of using the disclosed polymers, compositions, formulations, and/or dosage forms to treat various diseases or disorders, including those involving ion imbalances and/or fluid imbalances (e.g., overloads). In some embodiments, the disease is heart failure. In some embodiments, the disease is heart failure with chronic kidney disease. In some embodiments, the disease is end stage renal disease. In some embodiments, the disease is end stage renal disease with heart failure. In some embodiments, the disease is chronic kidney disease. In some embodiments, the disease is hypertension. In some embodiments, the disease is salt-sensitive hypertension. In some embodiments, the disease is refractory hypertension. In some embodiments, the disease involves an ion imbalance such as hyperkalemia, hypernatremia, hypercalcemia, etc. In some embodiments, the disease or disorder involves a fluid maldistribution or fluid overload state such as edema or ascites.

[0016] In some embodiments, the disease or disorder is the result of, or is associated with, administration of another agent (e.g., drug). For example, compositions, formulations, and/or dosage forms according to the present disclosure are useful in treating an increase in a subject's potassium level when co-administered with an agent (e.g., drug) known to cause increases in potassium levels, such as an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist, etc.

[0017] These and other embodiments will be described more fully by the detailed description and examples that follow.

DETAILED DESCRIPTION

[0018] The present disclosure relates generally to crosslinked cation-binding polymers comprising monomers that comprise carboxylate groups, e.g., crosslinked polyacrylic acid, and compositions, formulations, and/or dosage forms that contain the polymers, wherein the polymers further comprise calcium and/or magnesium cations (i.e., calcium cations, magnesium cations, or a mixture of calcium and magnesium cations), wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer (i.e., the polymer comprises an amount of calcium cations, an amount of magnesium cations, or an amount of a mixture of calcium and magnesium cations sufficient to provide calcium and/or magnesium counterions to about 5% to about 30% of the carboxylate groups in the polymer). Alternatively, the polymer comprises calcium and/or magnesium cations that are counterions to about 5% to about 10%, about 5% to about 15%), about 5% to about 20%>, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in the polymer. In some embodiments, the polymer comprises calcium and/or magnesium cations that are counterions to about 5%, about 10%, about 15%, about 20%, about 25%o, or about 30% of the carboxylate groups in the polymer. In some embodiments, the calcium and/or magnesium counterions consist of calcium cations. In other embodiments, the calcium and/or magnesium counterions consist of magnesium cations. In further embodiments, the calcium and/or magnesium cations consist of a mixture of calcium and magnesium cations. In some embodiments, the polymers may comprise sodium cations that are counterions to up to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 4% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 3% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 2% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to less than 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises calcium and/or magnesium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer, sodium cations as counterions up to about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to about 65% to about 90% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises calcium and/or magnesium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer (e.g., counterions that are not calcium, magnesium, or sodium are hydrogen). It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm of non-hydrogen elements), such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0019] The present disclosure also relates generally to crosslinked cation-binding polymers comprising monomers that comprise carboxylate groups, e.g., crosslinked polyacrylic acid, and compositions, formulations, and/or dosage forms that contain the polymers, wherein the polymers further comprise calcium and/or magnesium cations (i.e., calcium cations, magnesium cations, or a mixture of calcium and magnesium cations), wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (i.e., the polymer comprises an amount of calcium cations, an amount of magnesium cations, or an amount of a mixture of calcium and magnesium cations sufficient to provide calcium and/or magnesium counterions to about 15% to about 35% of the carboxylate groups in the polymer). Alternatively, the polymer comprises calcium and/or magnesium cations that are counterions to about about 15% to about 20%), about 15%> to about 25%>, about 15%> to about 30%>, about 15%> to about 35%>, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25% to about 30%), or about 25%> to about 35%> of the carboxylate groups in the polymer. In some embodiments, the polymer comprises calcium and/or magnesium cations that are counterions to about 15%>, about 20%>, about 25%>, about 30%>, or about 35%> of the carboxylate groups in the polymer. In some embodiments, the calcium and/or magnesium counterions consist of calcium cations. In other embodiments, the calcium and/or magnesium counterions consist of magnesium cations. In further embodiments, the calcium and/or magnesium cations consist of a mixture of calcium and magnesium cations. In some embodiments, the polymers may comprise sodium cations that are counterions to up to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 4% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 3% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 2% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to less than 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises calcium and/or magnesium cations as counterions to about 15% to about 35%) of the carboxylate groups on the polymer, sodium cations as counterions up to about 5%> of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to about 60% to about 80% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises calcium and/or magnesium cations as counterions to about 15%) to about 35% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer (e.g., counterions that are not calcium, magnesium, or sodium are hydrogen). It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm of non-hydrogen elements), such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0020] In some embodiments, crosslinked cation-binding polymers are provided that comprise monomers that comprise carboxylate groups, e.g., crosslinked polyacrylic acid, and compositions, formulations, and/or dosage forms that contain the polymers, wherein the polymers further comprise calcium cations, wherein the calcium cations are counterions to about 5%) to about 30%> of the carboxylate groups in the polymer (i.e., the polymer comprises an amount of calcium cations sufficient to provide calcium and/or magnesium counterions to about 5% to about 30%> of the carboxylate groups in the polymer). Alternatively, the polymer comprises calcium cations that are counterions to about 5% to about 10%), about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in the polymer. In some embodiments, the polymer comprises calcium cations that are counterions to about 5%, about 10%, about 15%, about 20%, about 25%), or about 30%> of the carboxylate groups in the polymer. In some embodiments, the calcium counterions consist of calcium cations. In some embodiments, the polymers may comprise sodium cations that are counterions to up to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 4% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 3% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 2% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to less than 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises calcium cations as counterions to about 5% to about 30%> of the carboxylate groups on the polymer, sodium cations as counterions up to about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to about 65%o to about 90%> of the carboxylate groups on the polymer. In some embodiments, the polymer comprises calcium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer (e.g. , counterions that are not calcium or sodium are hydrogen). It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0021] In some embodiments, crosslinked cation-binding polymers are provided that comprise monomers that comprise carboxylate groups, e.g., crosslinked polyacrylic acid, and compositions, formulations, and/or dosage forms that contain the polymers, wherein the polymers further comprise calcium cations, wherein the calcium cations are counterions to about 15%o to about 35% of the carboxylate groups in the polymer (i.e., the polymer comprises an amount of calcium cations sufficient to provide calcium and/or magnesium counterions to about 15% to about 35% of the carboxylate groups in the polymer). Alternatively, the polymer comprises calcium cations that are counterions to about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25% to about 30%), or about 25% to about 35% of the carboxylate groups in the polymer. In some embodiments, the polymer comprises calcium cations that are counterions to about 15%, about 20%), about 25%, about 30%, or about 35% of the carboxylate groups in the polymer. In some embodiments, the calcium counterions consist of calcium cations. In some embodiments, the polymers may comprise sodium cations that are counterions to up to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 4% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 3% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 2% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to less than 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises calcium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer, sodium cations as counterions up to about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to about 60%) to about 80% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises calcium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer (e.g. , counterions that are not calcium or sodium are hydrogen). It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0022] In some embodiments, crosslinked cation-binding polymers are provided that comprise monomers that comprise carboxylate groups, e.g., crosslinked polyacrylic acid, and compositions, formulations, and/or dosage forms that contain the polymers, wherein the polymers further comprise magnesium cations, wherein the magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer (i.e., the polymer comprises an amount of magnesium cations sufficient to provide magnesium counterions to about 5% to about 30% of the carboxylate groups in the polymer). Alternatively, the polymer comprises magnesium cations that are counterions to about 5% to about 10%), about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in the polymer. In some embodiments, the polymer comprises magnesium cations that are counterions to about 5%, about 10%, about 15%, about 20%), about 25%, about 30%, or about 35% of the carboxylate groups in the polymer. In some embodiments, the magnesium counterions consist of magnesium cations. In some embodiments, the polymers may comprise sodium cations that are counterions to up to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 4% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 3% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 2% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to less than 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises magnesium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer, sodium cations as counterions up to about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to about 65%) to about 90% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises magnesium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer (e.g., counterions that are not magnesium or sodium are hydrogen). It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0023] In some embodiments, crosslinked cation-binding polymers are provided that comprise monomers that comprise carboxylate groups, e.g., crosslinked polyacrylic acid, and compositions, formulations, and/or dosage forms that contain the polymers, wherein the polymers further comprise magnesium cations, wherein the magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer {i.e., the polymer comprises an amount of magnesium cations sufficient to provide magnesium counterions to about 15% to about 35% of the carboxylate groups in the polymer). Alternatively, the polymer comprises magnesium cations that are counterions to about 15% to about 20%), about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25% to about 30%), or about 25% to about 35% of the carboxylate groups in the polymer. In some embodiments, the polymer comprises magnesium cations that are counterions to about 15%, about 20%), about 25%, about 30%, or about 35% of the carboxylate groups in the polymer. In some embodiments, the magnesium counterions consist of magnesium cations. In some embodiments, the polymers may comprise sodium cations that are counterions to up to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 5% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 4% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 3% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 2% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to about 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises sodium cations that are counterions to less than 1% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises magnesium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer, sodium cations as counterions up to about 5% of the carboxylate groups on the polymer, and hydrogen cations {e.g., protons) as counterions to about 60%) to about 80% of the carboxylate groups on the polymer. In some embodiments, the polymer comprises magnesium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer and hydrogen cations {e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer (e.g. , counterions that are not magnesium or sodium are hydrogen). It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0024] In some embodiments, the polymer comprises calcium and/or magnesium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer, wherein counterions that are not calcium or magnesium are hydrogen (e.g., counterions that are not calcium or magnesium are hydrogen). In some embodiments, the polymer comprises calcium and/or magnesium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer. It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0025] In some embodiments, the polymer comprises calcium and/or magnesium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer, wherein counterions that are not calcium or magnesium are hydrogen (e.g., counterions that are not calcium or magnesium are hydrogen). In some embodiments, the polymer comprises calcium and/or magnesium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer. It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0026] In some embodiments, the polymer comprises calcium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer, wherein counterions that are not calcium are hydrogen (e.g., counterions that are not calcium are hydrogen). In some embodiments, the polymer comprises calcium cations as counterions to about 5% to about 30%) of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer. It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0027] In some embodiments, the polymer comprises calcium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer, wherein counterions that are not calcium are hydrogen (e.g., counterions that are not calcium are hydrogen). In some embodiments, the polymer comprises calcium cations as counterions to about 15% to about 35%) of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer. It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0028] In some embodiments, the polymer comprises magnesium cations as counterions to about 5%> to about 30%> of the carboxylate groups on the polymer, wherein counterions that are not magnesium are hydrogen (e.g., counterions that are not magnesium are hydrogen). In some embodiments, the polymer comprises magnesium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer. It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0029] In some embodiments, the polymer comprises magnesium cations as counterions to about 15%) to about 35% of the carboxylate groups on the polymer, wherein counterions that are not magnesium are hydrogen (e.g., counterions that are not magnesium are hydrogen). In some embodiments, the polymer comprises magnesium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer and hydrogen cations (e.g., protons) are counterions to the remainder or substantially the remainder of the carboxylate groups on the polymer. It is understood by those of skill in the art that these hydrogen cations are essentially hydrogen and may include small amounts (e.g., less than about 10,000 ppm) of non-hydrogen elements, such as iron, copper, aluminum, arsenic, mercury, manganese, phosphorous, lead, selenium, titanium, and/or zinc.

[0030] In some embodiments, the polymer comprises calcium cations as counterions to about 5% to about 30% of the carboxylate groups on the polymer, and sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer. In such embodiments, the polymer further comprises hydrogen cations (e.g. , protons) as counterions to all or substantially all of the carboxylate groups to which calcium and sodium are not counterions (e.g., "free carboxylates"), for example about 95% of the free carboxylates, about 96%) of the free carboxylates, about 97% of the free carboxylates, about 98%> of the free carboxylates, about 99% of the free carboxylates, about 99.5% of the free carboxylates, or about 100% of the free carboxylates. In some embodiments, the polymer comprises calcium cations as counterions to about 25% of the carboxylate groups on the polymer, sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to all or substantially all of the free carboxylates.

[0031] In some embodiments, the polymer comprises calcium cations as counterions to about 15%) to about 35% of the carboxylate groups on the polymer, and sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer. In such embodiments, the polymer further comprises hydrogen cations (e.g. , protons) as counterions to all or substantially all of the carboxylate groups to which calcium and sodium are not counterions (e.g., "free carboxylates"), for example about 95% of the free carboxylates, about 96%) of the free carboxylates, about 97% of the free carboxylates, about 98% of the free carboxylates, about 99% of the free carboxylates, about 99.5% of the free carboxylates, or about 100% of the free carboxylates. In some embodiments, the polymer comprises calcium cations as counterions to about 25% of the carboxylate groups on the polymer, sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to all or substantially all of the free carboxylates.

[0032] In some embodiments, the polymer comprises magnesium cations as counterions to about 5%) to about 30% of the carboxylate groups on the polymer and sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and further comprises hydrogen cations (e.g., protons) as counterions to all or substantially all of the carboxylate groups to which magnesium or sodium are not counterions (e.g., "free carboxylates"), for example about 95% of the free carboxylates, about 96% of the free carboxylates, about 97% of the free carboxylates, about 98% of the free carboxylates, about 99% of the free carboxylates, about 99.5% of the free carboxylates, or about 100% of the free carboxylates. In some embodiments, the polymer comprises calcium cations as counterions to about 25% of the carboxylate groups on the polymer, sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to all or substantially all of the free carboxylates.

[0033] In some embodiments, the polymer comprises magnesium cations as counterions to about 15% to about 35% of the carboxylate groups on the polymer and sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and further comprises hydrogen cations (e.g., protons) as counterions to all or substantially all of the carboxylate groups to which magnesium or sodium are not counterions (e.g., "free carboxylates"), for example about 95% of the free carboxylates, about 96% of the free carboxylates, about 97% of the free carboxylates, about 98% of the free carboxylates, about 99% of the free carboxylates, about 99.5% of the free carboxylates, or about 100% of the free carboxylates. In some embodiments, the polymer comprises calcium cations as counterions to about 25% of the carboxylate groups on the polymer, sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to all or substantially all of the free carboxylates.

[0034] The cross-linked polymer, e.g., cross-linked polyacrylate polymer, comprising calcium and/or magnesium counterions as disclosed herein may absorb at least about 20- fold, 30-fold, or 40-fold or more of its mass in fluid, such as a sodium solution (e.g., a solution of sodium salts, such as a saline solution or a physiological saline solution, for example, 0.154 molar total sodium concentration). For example, saline holding capacity for a disclosed cross-linked cation-binding polymer is determined in a buffered saline solution, e.g., a buffered saline solution that maintains pH at about 7.

[0035] Polymers as described herein and compositions that contain the polymers have unexpected cation binding and/or removal, and/or fluid binding and/or removal properties when administered to an individual (e.g., a mammal, such as a human) and therefore are useful for the treatment of a variety of diseases or disorders, including those involving ion and/or fluid imbalances (e.g., overloads). Surprisingly, ranges of calcium ions have been discovered and are disclosed herein that are optimized for maintaining the cation binding and/or removal properties of the polymer (e.g., for potassium and/or sodium) and/or the fluid binding and/or removal properties of the polymer in individuals, for example, humans. In some embodiments, inclusion of the calcium and/or magnesium ions on the polymer minimizes or prevents a change in acid base balance from administration of the polymer. In some embodiments, a neutral or substantially neutral acid/base status is maintained in the body of a subject, for example, a human subject. In some embodiments, an acid/base status (e.g., acid/base balance) associated with a subject does not change, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap, after administration of the polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer as described herein. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. The present disclosure also relates to methods of preparation of such polymers, and compositions, formulations, and dosage forms containing the polymers. The present disclosure also relates to methods of using such polymers and/or compositions, for example, in dosage forms, for the treatment of various diseases or disorders as disclosed herein, including, for example, heart failure (e.g., with or without chronic kidney disease), end stage renal disease (e.g., with or without heart failure), chronic kidney disease, hypertension (including, e.g., salt sensitive and refractory), hyperkalemia (e.g., any origin), hypernatremia (e.g., any origin), and/or fluid overload states (e.g., edema or ascities).

[0036] In some embodiments, compositions, formulations, and/or dosage forms are provided that comprise a base (for example, a calcium-containing base, such as calcium carbonate) and a cross-linked cation-binding polymer comprising monomers that comprise carboxylate groups, such as a cross-linked polyacrylate polymer, wherein the polymer further comprises calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups in the polymer (alternatively, calcium and/or magnesium cations that are counterions to about 5% to about 10%, about 5% to about 15%, about 5% to about 20%>, about 5% to about 25%, about 5% to about 30%>, about 10%> to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups). In some embodiments, the polymer comprises calcium and/or magnesium cations that are counterions to about 5%, about 10%>, about 15%, about 20%>, about 25%, or about 30%) of the carboxylate groups.

[0037] In some embodiments, compositions, formulations, and/or dosage forms are provided that comprise a base (for example, a calcium-containing base, such as calcium carbonate) and a cross-linked cation-binding polymer comprising monomers that comprise carboxylate groups, such as a cross-linked polyacrylate polymer, wherein the polymer further comprises calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, calcium and/or magnesium cations that are counterions to about 15% to about 20%, about 15% to about 25%), about 15%) to about 30%>, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25% to about 30%, or about 25% to about 35%) of the carboxylate groups). In some embodiments, the polymer comprises calcium and/or magnesium cations that are counterions to about 15%, about 20%, about 25%), about 30%), or about 35% of the carboxylate groups.

[0038] The present disclosure also provides crosslinked cation-binding polymers comprising crosslinked polyacrylic acid monomers, and compositions, formulations, and/or dosage forms that contain the polymers, wherein the polymers further comprise calcium cations, and wherein the calcium cations are counterions to about 4.0 to about 8.9% of the carboxylate groups in the polymer; sodium content less than or equal to 5000 ppm; heavy metals less than 20 ppm; total residual chloride less than or equal to 2000 ppm; loss on drying less than 5%, saline holding capacity greater than 33 g saline/g CLP (at 240 minutes), appearance that is white to off white, opaque or translucent particles; and/or IR spectrum that conforms to reference spectrum.

[0039] Non-limiting examples of suitable carboxylic acid-containing monomers for production of a polymer as described herein include, for example: acrylic acid and its salts, methacrylic acid and its salts, crotonic acid and its salts, tiglinic acid and its salts, 2-methyl- 2-butenoic acid (Z) and its salts, 3-butenoic acid (vinylacetic acid) and its salts, 1- cyclopentene carboxylic acid and its salts, 2-cyclopentene carboxylic acid and its salts; and unsaturated dicarboxylic acids and their salts, such as maleic acid, fumaric acid, itaconic acid, glutaconic acid, and their salts. Polymers may include copolymers of the above monomers. Other cross-linked cation-binding polyelectrolyte polymers may be based on sulfonic acids and their salts, phosphonic acids and their salts, or amines and their salts, for example, acrylic acid with sulfonic acids or salts thereof, phosphonic acids or salts thereof, or amines and their salts. Regardless of the choice of monomer, polymers useful in the present disclosure contain a plurality of carboxylic acid (-C(O)OH) and/or carboxylate (- C(0)0 ) groups.

[0040] Polymers of the present disclosure are crosslinked. Any crosslinker known in the art may be used. Crosslinking agents contemplated for use in the present disclosure, include, for example, diethelyeneglycol diacrylate (diacryl glycerol), triallylamine, tetraallyloxy ethane, allylmethacrylate, 1,1,1-trimethylolpropane triacrylate (TMPTA), divinyl benzene, and divinyl glycol. The amount of crosslinking agent used may vary depending on the absorbent characteristics desired. In general, increasing amounts of crosslinking agent will yield polymers with increasing degrees of crosslinking. Such polymers with higher degrees of crosslinking may be preferred over less crosslinked polymers when fluid absorption is unnecessary. For polymers of the present disclosure, an amount of crosslinking may be chosen that yields a polymer with an in vitro saline absorption capacity {e.g., saline holding capacity) of greater than about 20 times its own weight. For the purposes of this disclosure saline absorption capacity (e.g., saline holding capacity) is measured in a saline solution buffered to pH 7. For example, the amount of crosslinker used to crosslink polymers according to the present disclosure may range from about 0.08 mol% to about 0.2 mol% or alternatively from about 0.025 mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.% to about 0.3 mol.% or from about 0.025 mol.% to about 0.17 mol.% or from about 0.025 mol.% to about 0.34 mol.%.

[0041] In certain exemplary embodiments, the crosslinked cation-binding polymer, as described, for example, for inclusion in compositions, formulations, and/or dosage forms and/or for use in methods for treatment of various diseases or disorders as described herein, and/or for use in methods for cation binding and/or removal, and/or fluid binding and/or removal, as described herein, is a crosslinked polyacrylate polymer {i.e., derived from acrylic acid monomers or a salt thereof) that comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer, and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer. For example, the polymer may be a polyacrylate polymer crosslinked with about 0.08 mol% to about 0.2 mol% crosslinker or alternatively from about 0.025 mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.% to about 0.3 mol.%., and for example, may comprise an in vitro saline absorption capacity {e.g., saline holding capacity) of at least about 20 times its weight (e.g., at least about 20 grams of saline per gram of polymer, or "g/g")_> at least about at least about 30 times its weight, at least about 40 times its weight, at least about 50 times its weight, at least about 60 times its weight, at least about 70 times its weight, at least about 80 times its weight, at least about 90 times its weight, at least about 100 times its weight, or more. In some embodiments, the crosslinked polyacrylate polymer comprises individual particles or particles that are agglomerated (for example, flocculated) to form a larger particle, wherein the individual or agglomerated particle diameter is about 1 to about 10,000 microns (alternatively, about 1 micron to about 10 microns, about 1 micron to about 50 microns, about 10 microns to about 50 microns, about 10 microns to about 200 microns, about 50 microns to about 100 microns, about 50 microns to about 200 microns, about 50 microns to about 1000 microns, about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or about 5000 microns to about 10,000 microns. For example, a polymer, including a polyacrylate polymer, may have a particle size of about 212 microns to about 500 microns, a particle size from about 75 microns to about 150 microns, or a particle size of about 75 microns or less. In some embodiments, no less than about 70% of the polymer has a particle size of about 212 microns to about 500 microns, a particle size from about 75 microns to about 150 microns, or a particle size of about 75 microns or less. In one embodiment, the polyacrylate polymer is in the form of small particles that flocculate to form agglomerated particles with a diameter of about 1 micron to about 10 microns or about 0.1 microns to about 20 microns. Such polyacrylate polymers may include polycarbophil.

[0042] In certain exemplary embodiments, the crosslinked cation-binding polymer, as described, for example, for inclusion in compositions, formulations, and/or dosage forms and/or for use in methods for treatment of various diseases or disorders as described herein, and/or for use in methods for cation binding and/or removal, and/or fluid binding and/or removal, as described herein, is a crosslinked polyacrylate polymer {i.e., derived from acrylic acid monomers or a salt thereof) that comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer, and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer. For example, the polymer may be a polyacrylate polymer crosslinked with about 0.08 mol% to about 0.2 mol% crosslinker or alternatively from about 0.025 mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.% to about 0.3 mol.%., and for example, may comprise an in vitro saline absorption capacity {e.g., saline holding capacity) of at least about 20 times its weight (e.g., at least about 20 grams of saline per gram of polymer, or "g/g")_> at least about at least about 30 times its weight, at least about 40 times its weight, at least about 50 times its weight, at least about 60 times its weight, at least about 70 times its weight, at least about 80 times its weight, at least about 90 times its weight, at least about 100 times its weight, or more. In some embodiments, the crosslinked polyacrylate polymer comprises individual particles or particles that are agglomerated (for example, flocculated) to form a larger particle, wherein the individual or agglomerated particle diameter is about 1 to about 10,000 microns (alternatively, about 1 micron to about 10 microns, about 1 micron to about 50 microns, about 10 microns to about 50 microns, about 10 microns to about 200 microns, about 50 microns to about 100 microns, about 50 microns to about 200 microns, about 50 microns to about 1000 microns, about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or about 5000 microns to about 10,000 microns. In one embodiment, the polyacrylate polymer is in the form of small particles that flocculate to form agglomerated particles with a diameter of about 1 micron to about 10 microns.

[0043] In some embodiments, administration of such a crosslinked polyacrylate polymer, comprising comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer, does not change or does not significantly change acid/base status {e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, a crosslinked polyacrylate polymer, comprising comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer, is administered with an added base {e.g., up to about 0.9 equivalents of added base per equivalents of carboxylate groups in the polymer), and such administration of the polymer and base does not change or does not significantly change acid/base status {e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, such a crosslinked polyacrylate polymer, comprising calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer, may be administered, optionally with added base as described herein, to an individual for removal of fluid and/or ions, for example, sodium and/or potassium cations, wherein such administration does not change or does not significantly change acid/base status (e.g. , acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject.

[0044] In some embodiments, administration of such a crosslinked polyacrylate polymer, comprising comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer, does not change or does not significantly change acid/base status (e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, a crosslinked polyacrylate polymer, comprising comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15%) to about 35% of the carboxylate groups in the polymer, is administered with an added base (e.g., up to about 0.8 equivalents of added base per equivalents of carboxylate groups in the polymer), and such administration of the polymer and base does not change or does not significantly change acid/base status (e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject.. In some embodiments, such a crosslinked polyacrylate polymer, comprising calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer, may be administered, optionally with added base as described herein, to an individual for removal of fluid and/or ions, for example, sodium and/or potassium cations, wherein such administration does not change or does not significantly change acid/base status (e.g. , acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject.

[0045] As used herein, the term "cation" or "cations" refers to atomic, polyatomic, or molecular ions having a net positive charge, and may include one such cation or a combination of more than one cation. Non-limiting examples of cations include: hydrogen cations (H⁺), sodium cations (Na⁺), potassium cations (K⁺), magnesium cations (Mg²⁺), calcium cations (Ca²⁺), iron cations (e.g., Fe²⁺, Fe³⁺), and combinations thereof. As used herein, the term "non-hydrogen cation" or "non-hydrogen cations" refers to cation(s) (e.g., as defined above) other than hydrogen (H⁺; proton). Mixtures of more than one cation are within the scope of the terms cation or cations, as used herein. Counterions to carboxylate groups on the polymers described herein are cations. Crosslinked cation-binding polymers as disclosed herein can be described by the percentage of carboxylate groups for which one or more cation serves as a counterion. For example, a polymer according to the present disclosure may be referred to as "25% calcium" to indicate that calcium cations are counterions to about 25% of the carboxylate groups in the polymer. Or, when expressed as a molar ratio, a "25% calcium" polymer according to the present disclosure includes about 12.5 moles of calcium cations (i.e., divalent Ca²⁺ cations) per 100 moles of carboxylate groups in the polymer (e.g., a mole fraction with respect to calcium of 0.125). In another example, a " 15% magnesium" polymer according to the present disclosure indicates that magnesium cations (i.e., divalent Mg²⁺ cations) are counterions to about 15% of the carboxylate groups in the polymer (e.g., a mole fraction with respect to magnesium of 0.075). A " 15%) calcium/15%) magnesium" polymer according to the present disclosure likewise indicates that calcium cations are counterions to about 15% of the carboxylate groups in the polymer and magnesium cations are counterions to about 15% of the carboxylate groups in the polymer (e.g., mole fractions of 0.075 for calcium and 0.075 for magnesium). In some embodiments, hydrogen cations (e.g., protons) may be counterions to all or substantially all of the carboxylate groups for which calcium and/or magnesium are not counterions. [0046] In some embodiments, crosslinked cation-binding polymers according to the present disclosure comprise calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups in the polymer, and further comprise one or more additional cations. In some embodiments, the one or more additional cations are monovalent cations such as sodium, potassium, ammonium, arginine, lysine, choline, histidine, serine, and the like. In some embodiments, the one or more additional cations are divalent cations such as iron(II), zinc, a lanthanide, and the like. In some embodiments, the one or more cations are trivalent cations such as aluminum, iron(III), and the like. Nomenclature of a polymer which comprises one or more additional cations thus depends on the identity of the one or more additional cations, the amount of each of the one or more additional cations, and the valency of each of the one or more additional cations. For example, a polymer according to the present disclosure denoted as "25% calcium/9%) iron (III) " would indicate that calcium cations are counterions to about 25% of the carboxylate groups in the polymer, trivalent iron cations (Fe³⁺ cations) are counterions to about 9% of the carboxylate groups in the polymer, and hydrogen cations (e.g., protons) are counterions to about 66%o of the carboxylate groups in the polymer. To avoid any doubt, a "25% calcium/9% trivalent iron" polymer according to the present disclosure comprises about 12.5 moles of calcium cations and about 3 moles of trivalent iron cations per 100 moles of carboxylate groups in the polymer (e.g., 0.25 equivalents of calcium cations and 0.9 equivalents of iron).

[0047] In some embodiments, crosslinked cation-binding polymers according to the present disclosure comprise calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups in the polymer, and further comprise one or more additional cations. In some embodiments, the one or more additional cations are monovalent cations such as sodium, potassium, ammonium, arginine, lysine, choline, histidine, serine, and the like. In some embodiments, the one or more additional cations are divalent cations such as iron(II), zinc, a lanthanide, and the like. In some embodiments, the one or more cations are trivalent cations such as aluminum, iron(III), and the like. Nomenclature of a polymer which comprises one or more additional cations thus depends on the identity of the one or more additional cations, the amount of each of the one or more additional cations, and the valency of each of the one or more additional cations. For example, a polymer according to the present disclosure denoted as "25% calcium/9%) iron (III) " would indicate that calcium cations are counterions to about 25% of the carboxylate groups in the polymer, trivalent iron cations (Fe³⁺ cations) are counterions to about 9% of the carboxylate groups in the polymer, and hydrogen cations (e.g., protons) are counterions to about 66% of the carboxylate groups in the polymer. To avoid any doubt, a "25% calcium/9% trivalent iron" polymer according to the present disclosure comprises about 12.5 moles of calcium cations and about 3 moles of trivalent iron cations per 100 moles of carboxylate groups in the polymer (e.g., 0.25 equivalents of calcium cations and 0.9 equivalents of iron).

[0048] Determination of the percentage of cations that serve as counterions to carboxylate groups in a polymer as disclosed herein can be accomplished by any suitable means known in the art. When the polymer comprises calcium as a counterion to the carboxylate groups of the polymer, the polymer may be referred to as Ca-CLP. When the polymer comprises magnesium as a counterion to the carboxylate groups of the polymer, the polymer may be referred to as Mg-CLP. When the polymer comprises sodium as a counterion to the carboxylate groups of the polymer, the polymer may be referred to as Na- CLP. For example and without limitation, the polymer may be analyzed with an inductively coupled plasma ("ICP") spectrometer (e.g., by mass spectroscopy (ICP-MS), atomic emission spectroscopy (ICP-AES), or optical emission spectroscopy (ICP-OES)) using methods known to those skilled in the art. The percentage of cations serving as counterions to carboxylate groups in the polymer (e.g., calcium and/or magnesium counterions to the carboxylate groups in the polymer) may be confirmed, for example, by ICP spectroscopy, atomic absorption spectroscopy, ion chromatography, or similar analytic methods. Such methods are well known in the art.

[0049] Cation content of polymers disclosed herein may be determined by ICP, including ICP-AES, ICP-MS, or ICP-OES (see, e.g., Example 6). In some exemplary embodiments, content of calcium, magnesium, sodium, potassium, and/or iron may be determined. The ICP analysis may be reported in g cation/g polymer, which may then be converted to weight percent (wt.%). Weight percent may be converted to % of cations that are counterions to the carboxylate groups in the polymer. The % of cations that are counterions to the carboxylate groups in the polymer determined in different measurements may vary by ±20% or less. For example, the determination of 15% to 35% calcium cations as counterions to carboxylate groups in the polymer may vary in different measurements by ICP (e.g., 15% ±20% to 35% ±20%). Additionally, for example, the determination of 5% to 30% calcium cations as counterions to carboxylate groups in the polymer may vary in different measurements by ICP (e.g., 5% ±20% to 30% ±20%).

[0050] For example, an ICP analysis of a crosslinked cation-binding polyacrylate polymer as disclosed herein, comprising hydrogen cations (e.g., protons), calcium cations and acrylic acid monomers having carboxylate groups, reporting about 4 wt.% to about 9 wt.% calcium cations corresponds to a polyacrylate polymer wherein about 15% to about 35%) carboxylate groups are bound to calcium counterions, as calculated by the following formula:

[x]%Ca-CLP = (72.06)(wt.% Ca)/(20.05 - (0.19)(wt.% Ca))

[0051] In an embodiment, an ICP analysis that reports calcium content at 5.7 wt.% calcium represents a polyacrylate polymer with about 22% of the carboxylate groups bound to calcium (e.g., calcium cations are counterions to about 22% of the carboxylate groups in the polymer), as calculated by the following formula:

[x]%Ca-CLP = (72.06)(5.7)/(20.05 - (0.19)(5.7)) = 22% Ca-CLP

[0052] In another embodiment, an ICP analysis that reports calcium content at 5.6 wt.% represents a 21% Ca-CLP) polymer (e.g., calcium cations are counterions to about 21% of the carboxylate groups in the polymer). In another embodiment, an ICP analysis that reports calcium content at 7.4 wt.% represents a 29% Ca-CLP polymer (e.g., calcium cations are counterions to about 29% of the carboxylate groups in the polymer). In Examples 13-14, Ca-CLP of 4.0 - 8.9 wt.% (e.g., corresponding to 15% to 35%, including 21%, 22%, and 29% Ca-CLP, designated as 25% Ca-CLP), was used.

[0053] Conversely, the weight percent calcium of a polyacrylate polymer having cations comprising hydrogen (e.g., protons) and calcium can be calculated based on the percentage of carboxylate groups bound to calcium according to the following equation:

wt.% Ca = ((20.05)([x]% Ca-CLP))/((72.06) + (0.19)([x]% Ca-CLP))

[0054] In an embodiment, a 25% Ca-CLP polyacrylate polymer has 6.52 wt% calcium according to the following equation:

wt.% Ca = ((20.05)(25% Ca-CLP)/((72.06) + (0.19)(25% Ca-CLP)) = 6.52 wt.% Ca.

[0055] For example, an ICP analysis that reports magnesium content at 2.5 - 5.6 wt.% magnesium represents about 15% to about 35% magnesium as counterions to carboxylate groups in a polyacrylate polymer (e.g., about 15%> Mg-CLP to about 35%> Mg-CLP), as calculated by the following formula for a polyacrylate polymer:

[x]%Mg-CLP = (72.06)(wt.% Mg)/(12.15 - (0.1 l(wt.% Mg)) [0056] For example, an ICP analysis that reports sodium content at 0.030 wt.% sodium represents about 0.09% sodium cations as counterions to carboxylate groups in the polymer, as calculated by the following formula for a polyacrylate polymer:

[x]%Na-CLP = (72.06)(wt.% Na)/(23.0 - (0.23)(wt.% Na))

[0057] For 0.03 wt% sodium, the calculation is as follows:

[x]%Na-CLP = (72.06)(0.030)/(23.0 - (0.23)(0.030)) = 0.09% sodium counterions to the carboxylate groups in the polymer.

[0058] In an embodiment, an ICP analysis that reports sodim content at 0.031 wt.% sodium represents a polacrylate polymer having sodium counterions to about 0.10% of the carboxylate groups in the polymer.

[0059] In another embodiment, an ICP analysis that reports sodium content at 0.035 wt.%) represents a polyacrylate polymer having sodium counterions to about 0.1 1% sodium of the carboxylate groups in the polymer.

[0060] The above equations are useful for determination of percentage cation when a single type of non-hydrogen cation (e.g., calcium) is present as a counterion to carboxylate groups in the polymer. As understood by persons skilled in the art, the above equations are modified when combinations of types cations are present (e.g., calcium, magnesium, and/or sodium).

[0061] Compositions, formulations, and/or dosage forms comprising a polymer as disclosed herein may optionally additionally comprise and/or be co-administered with a base (alternatively termed an alkali). As used herein, the term base may refer to a suitable compound or mixture of compounds that is capable of increasing the pH of the blood or other bodily fluids. Exemplary bases include, but are not limited to, calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium hydroxide, sodium bicarbonate, potassium bicarbonate, aluminum hydroxide, calcium citrate. Exemplary bases also include calcium acetate, calcium oxide, potassium citrate, and potassium acetate. Generally, inorganic and organic bases can be used, provided they are physiologically and/or clinically acceptable. To be acceptable, the dose and route of administration of the specific base are important considerations. For example, oral administration of even small amounts of sodium hydroxide would cause local tissue damage and would not be acceptable on this basis while administration of intermittent, small amounts of sodium hydroxide intravenously is performed routinely. Similarly, though lithium carbonate or rubidium acetate would be an acceptable base, only small amounts could be used due to the effects of the lithium or the rubidium, regardless of the route of administration.

[0062] In some embodiments, compositions, formulations, and/or dosage forms comprising a polymer as disclosed herein additionally comprise a base that may be present in an amount sufficient to provide up to about 0.9 equivalents of base per equivalent of carboxylate groups in the polymer. For example, the composition, formulation, and/or dosage form may contain a disclosed polymer that contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups (i.e., calcium and/or magnesium counterions that are added during manufacture of the polymer) and base that is added during preparation or formulation of the composition, formulation, and/or dosage form in an amount sufficient to provide up to about 0.9 equivalents per equivalent of carboxylate groups in the polymer.

[0063] In some embodiments, compositions, formulations, and/or dosage forms comprising a polymer as disclosed herein additionally comprise a base that may be present in an amount sufficient to provide up to about 0.8 equivalents of base per equivalent of carboxylate groups in the polymer. For example, the composition, formulation, and/or dosage form may contain a disclosed polymer that contains calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups (i.e., calcium and/or magnesium counterions that are added during manufacture of the polymer) and base that is added during preparation or formulation of the composition, formulation, and/or dosage form in an amount sufficient to provide up to about 0.8 equivalents per equivalent of carboxylate groups in the polymer.

[0064] In some embodiments, the optionally added base is present, for example, in a composition, formulation, and/or dosage form comprising a disclosed polymer and/or is co- administered with a disclosed polymer, in an amount sufficient to provide an equivalents ratio of up to about 90 equivalents of base per equivalent (e.g., mole) of carboxylic acid groups in the polymer. As used herein, the term "equivalents ratio" ("ER") refers to the ratio between the number of units (e.g. , equivalents) of base present in the composition and the number of units (e.g. , moles) of carboxylic acid groups in the polymer. A monobasic base provides one equivalent of base per mole of monobasic base. A dibasic base provides two equivalents of base per mole of dibasic base. A tribasic base provides three equivalents of base per mole of tribasic base. For example, a composition comprising a polymer derived from polymerization and crosslinking of 1.0 mole of acrylic acid monomers may contain up to about 0.8 moles of a monobasic base, such as a bicarbonate. If a dibasic base is used, such as a carbonate, a composition comprising 1.0 mole of carboxylic acid groups may contain up to about 0.425 moles of the dibasic base.

[0065] In some embodiments, compositions of the present disclosure comprise a monobasic base (e.g., one equivalent per mole) present in an amount sufficient to provide from up to about 0.8 moles of base per mole of carboxylic acid groups in the polymer, for example about 0.5 moles of base, about 0.1 moles of base, about 0.15 moles of base, about 0.2 moles of base, about 0.25 moles of base, about 0.3 moles of base, about 0.35 moles of base, about 0.4 moles of base, about 0.45 moles of base, about 0.5 moles of base, about 0.55 moles of base, about 0.6 moles of base, about 0.65 moles of base, about 0.7 moles of base, about 0.75 moles of base, or about 0.8 moles of base per mole of carboxylic acid groups in the polymer. In some embodiments, compositions of the present disclosure comprise a monobasic base present in an amount sufficient to provide from about 0.2 moles of base to about 0.8 moles of base of base, for example about 0.2 moles of base, about 0.25 moles of base, about 0.3 moles of base, about 0.35 moles of base, about 0.4 moles of base, about 0.45 moles of base, 0.5 moles of base, about 0.55 moles of base, about 0.6 moles of base, about 0.65 moles of base, about 0.7 moles of base, about 0.75 moles of base, about 0.8 moles of base, about 0.85 moles of base, or about 0.90 moles of base per mole of carboxylate groups in the polymer. In some embodiments, compositions of the present disclosure comprise a monobasic base present in an amount sufficient to provide from about 0.3 moles of base to about 0.6 moles of base of base, for example about 0.3 moles of base, about 0.35 moles of base, about or 0.4 moles of base, about 0.45 moles of base, about 0.5 moles of base, about 0.55 moles of base, or about 0.6 moles of base per mole of carboxylate groups in the polymer. In some embodiments, compositions of the present disclosure comprise a monobasic base present in an amount sufficient to provide about 0.5 moles of base per mole of carboxylate groups in the polymer.

[0066] In some embodiments, compositions of the present disclosure comprise a dibasic base (e.g., two equivalents per mole) present in an amount sufficient to provide from up to about 0.425 moles of base per mole of carboxylic acid groups in the polymer, for example about 0.05 moles of base, about 0.075 moles of base, about 0.1 moles of base, about 0.125 moles of base, about 0.15 moles of base, about 0.175 moles of base, about 0.2 moles of base, about 0.225 moles of base, about 0.25 moles of base, about 0.275 moles of base, about 0.3 moles of base, about 0.325 moles of base, about 0.35 moles of base, about 0.375 moles of base, about 0.4 moles of base, or about 0.425 moles of base per mole of carboxylic acid groups in the polymer. In some embodiments, compositions of the present disclosure comprise a dibasic base present in an amount sufficient to provide from about 0.1 moles of base to about 0.4 moles of base of base, for example about 0.1 moles of base, about 0.125 moles of base, about 0.15 moles of base, about 0.175 moles of base, about 0.2 moles of base, about 0.225 moles of base, about 0.25 moles of base, about 0.275 moles of base, about 0.3 moles of base, about 0.325 moles of base, about 0.35 moles of base, about 0.375 moles of base, or about 0.4 moles of base of base per mole of carboxylate groups in the polymer. In some embodiments, compositions of the present disclosure comprise a dibasic base present in an amount sufficient to provide from about 0.15 moles of base to about 0.25 moles of base of base, for example about 0.15 moles of base, about 0.175 moles of base, about or 0.2 moles of base, about 0.225 moles of base, or about 0.5 moles of base per mole of carboxylate groups in the polymer. In some embodiments, compositions of the present disclosure comprise a dibasic base present in an amount sufficient to provide about 0.25 moles of base per mole of carboxylate groups in the polymer.

[0067] In some embodiments, compositions of the present disclosure comprise a tribasic base (e.g. , three equivalents per mole) present in an amount sufficient to provide up to about 0.28 moles of base per mole of carboxylic acid groups in the polymer, for example about 0.017 moles of base, about 0.033 moles of base, about 0.05 moles of base, 0.065 moles of base, about 0.07 moles of base, about 0.075 moles of base, about 0.08 moles of base, about 0.085 moles of base, about 0.09 moles of base, about 0.095 moles of base, about 0.1 moles of base, about 0.105 moles of base, about 0.1 1 moles of base, about 0.1 15 moles of base, about 0.12 moles of base, about 0.125 moles of base, about 0.13 moles of base, about 0.135 moles of base, about 0.14 moles of base, about 0.145 moles of base, about 0.15 moles of base, about 0.155 moles of base, about 0.16 moles of base, about 0.165 moles of base, about 0.17 moles of base, about 0.175 moles of base, about 0.18 moles of base, about 0.185 moles of base, about 0.19 moles of base, about 0.195 moles of base, about 0.2 moles of base, about 0.205 moles of base, about 0.21 moles of base, about 0.215 moles of base, about 0.22 moles of base, about 0.225 moles of base, about 0.23 moles of base, about 0.235 moles of base, about 0.24 moles of base, about 0.245 moles of base, about 0.25 moles of base, about 0.255 moles of base, about 0.26 moles of base, about 0.265 moles of base, about 0.27 moles of base, about 0.275 moles of base, or about 0.28 moles of base per mole of carboxylic acid groups in the polymer. In some embodiments, compositions of the present disclosure comprise a tribasic base present in an amount sufficient to provide from about 0.065 moles of base to about 0.26 moles of base of base, for example about 0.065 moles of base, about 0.07 moles of base, about 0.075 moles of base, about 0.08 moles of base, about 0.085 moles of base, about 0.09 moles of base, about 0.095 moles of base, about 0.1 moles of base, about 0.105 moles of base, about 0.1 1 moles of base, about 0.1 15 moles of base, about 0.12 moles of base, about 0.125 moles of base, about 0.13 moles of base, about 0.135 moles of base, about 0.14 moles of base, about 0.145 moles of base, about 0.15 moles of base, about 0.155 moles of base, about 0.16 moles of base, about 0.165 moles of base, about 0.17 moles of base, about 0.175 moles of base, about 0.18 moles of base, about 0.185 moles of base, about 0.19 moles of base, about 0.195 moles of base, about 0.2 moles of base, about 0.205 moles of base, about 0.21 moles of base, about 0.215 moles of base, about 0.22 moles of base, about 0.225 moles of base, about 0.23 moles of base, about 0.235 moles of base, about 0.24 moles of base, about 0.245 moles of base, about 0.25 moles of base, about 0.255 moles of base, or about 0.26 moles of base per mole of carboxylate groups in the polymer. In some embodiments, compositions of the present disclosure comprise a tribasic base present in an amount sufficient to provide from about 0.1 moles of base to about 0.2 moles of base of base, for example about 0.1 moles of base, about 0.105 moles of base, about 0.1 1 moles of base, about 0.1 15 moles of base, about 0.12 moles of base, about 0.125 moles of base, about 0.13 moles of base, about 0.135 moles of base, about 0.14 moles of base, about 0.145 moles of base, about 0.15 moles of base, about 0.155 moles of base, about 0.16 moles of base, about 0.165 moles of base, about 0.17 moles of base, about 0.175 moles of base, about 0.18 moles of base, about 0.185 moles of base, about 0.19 moles of base, about 0.195 moles of base, or about 0.2 moles of base per mole of carboxylate groups in the polymer. In some embodiments, compositions of the present disclosure comprise a tribasic base present in an amount sufficient to provide about 0.17 moles of base per mole of carboxylate groups in the polymer.

[0068] In some embodiments, compositions, formulations, and/or dosage forms of the present disclosure comprise more than one base (e.g., one or more monobasic bases, one or more dibasic bases, one or more tribasic bases, etc.). In such embodiments, the compositions comprise an amount of each base such that the total number of equivalents of base present is up to about 0.9 equivalents per mole of carboxylic acid groups in the polymer, for example, about 0.2 equivalents to about 0.9 equivalents, or about 0.3 equivalents to about 0.6 equivalents, per mole of carboxylic acid groups in the polymer. [0069] Thus, as one example embodiment, a composition according to the present invention that comprises 1.0 mole of carboxylic acid groups and 0.1 moles of sodium bicarbonate may also comprise from about 0.05 moles to about 0.375 moles of a dibasic base such as magnesium carbonate. In such an embodiment, the total equivalents of base would be equal to 0.1 + (2) (about 0.05 to about 0.375), or about 0.2 to about 0.8 equivalents of base.

[0070] In some embodiments, the base is present in an amount sufficient to provide from up to about 0.9 equivalents of base, for example about 0.05 equivalents, about 0.1 equivalents, about 0.15 equivalents, 0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about 0.35 equivalents, about 0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.55 equivalents, about 0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75 equivalents, about 0.8 equivalents, about 0.8 equivalents, or about 0.9 equivalents of base per equivalent of carboxylic acid groups in the polymer. In some embodiments, the base is present in an amount sufficient to provide from about 0.5 equivalents to about 0.9 equivalents of base, for example about 0.5 equivalents, about 0.55 equivalents, about 0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75 equivalents, about 0.8 equivalents, about 0.85 equivalents, or about 0.9 equivalents of base per equivalent of carboxylate groups in the polymer. In some embodiments, the base is present in an amount sufficient to provide from about 0.3 equivalents to about 0.6 equivalents of base, for example, about 0.3 equivalents, about 0.35 equivalents, about 0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.55 equivalents, or about 0.6 equivalents base per equivalent of carboxylate groups in the polymer. In some embodiments, the base is present in an amount sufficient to provide about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer.

[0071] In some embodiments, a composition, formulation, and/or dosage form contains a polymer that comprises calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups (e.g.., calcium and/or magnesium counterions that are added during manufacture of the polymer) and added base (e.g., base added during preparation or formulation of the composition, formulation, and/or dosage form that contains the polymer) in an amount sufficient to provide up to about 0.9 equivalents per equivalent of carboxylate groups in the polymer. In one embodiment, the disclosed polymer contains about 25% calcium and/or magnesium (e.g.., calcium and/or magnesium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises about 0.5 equivalents of added base. In another embodiment, the disclosed polymer contains about 25% calcium and/or magnesium (e.g.., calcium and/or magnesium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises about 0.35 equivalents of added base.

[0072] In some embodiments, a composition, formulation, and/or dosage form contains a polymer that comprises calcium and/or magnesium cations that are counterions to about 15% to about 35%) of the carboxylate groups (e.g.., calcium and/or magnesium counterions that are added during manufacture of the polymer) and added base (e.g., base added during preparation or formulation of the composition, formulation, and/or dosage form that contains the polymer) in an amount sufficient to provide up to about 0.8 equivalents per equivalent of carboxylate groups in the polymer. In one embodiment, the disclosed polymer contains about 25% calcium and/or magnesium (e.g.., calcium and/or magnesium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises about 0.5 equivalents of added base. In another embodiment, the disclosed polymer contains about 25% calcium and/or magnesium (e.g.., calcium and/or magnesium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises about 0.35 equivalents of added base.

[0073] In some embodiments, a composition, formulation, and/or dosage form contains a crosslinked polyacrylate polymer that comprises calcium and/or magnesium cations that are counterions to about 5% to about 30%> of the carboxylate groups (e.g., calcium and/or magnesium counterions that are added during manufacture of the polymer) and added base (e.g.., base added during preparation or formulation of the composition, formulation, and/or dosage form that contains the polymer) in an amount sufficient to provide up to about 0.9 equivalents per equivalent of carboxylate groups in the polymer. In one embodiment, the crosslinked polyacrylate polymer contains about 25% calcium (e.g.., calcium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises about 0.5 equivalents of base. In another embodiment, the crosslinked polyacrylate polymer contains about 25% calcium (e.g., calcium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises about 0.35 equivalents of base. [0074] In some embodiments, a composition, formulation, and/or dosage form contains a crosslinked polyacrylate polymer that comprises calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups (e.g., calcium and/or magnesium counterions that are added during manufacture of the polymer) and added base (e.g.., base added during preparation or formulation of the composition, formulation, and/or dosage form that contains the polymer) in an amount sufficient to provide up to about 0.8 equivalents per equivalent of carboxylate groups in the polymer. In one embodiment, the crosslinked polyacrylate polymer contains about 25% calcium (e.g.., calcium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises about 0.5 equivalents of base. In another embodiment, the crosslinked polyacrylate polymer contains about 25% calcium (e.g., calcium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises about 0.35 equivalents of base.

[0075] In some embodiments, a disclosed polymer, e.g., a crosslinked polyacrylate polymer, comprises calcium and/or magnesium cations that are counterions to about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35% of the carboxylate groups in the polymer (i.e., calcium and/or magnesium counterions added during manufacture of the polymer) and a composition, formulation, and/or dosage form that contains the polymer comprises 0.05 equivalents, about 0.1 equivalents, about 0.15 equivalents, about 0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about 0.35 equivalents, about 0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.6 equivalents, about 0.7 equivalents, about 0.75 equivalents, about 0.8 equivalents, about 0.85 equivalents, or about 0.9 equivalents of added base per equivalent of carboxylic acid groups in the polymer (e.g., base added during preparation and/or formulation of the composition, formulation, and/or dosage form that contains the polymer).

[0076] In some embodiments, a polymer or composition, formulation, or dosage form containing a polymer as disclosed herein is administered with added base in the same composition, formulation, or dosage form with the polymer or in a separate composition, formulation, or dosage form from the polymer, wherein the base is present in an amount sufficient to provide up to about 0.9 equivalents of base per equivalent of carboxylate groups in the polymer (alternatively, the base is present in an amount sufficient to provide about 0.3 to about 0.6 or about 0.35 to about 0.5 equivalents per equivalent of carboxylate groups in the polymer; alternatively, the base is present in an amount sufficient to provide about 0.65 to about 0.75, such as about 0.66, about 0.70, about 0.73, about 0.74 equivalents of base per equivalent of carboxylate groups in the polymer). For example, a disclosed polymer that contains calcium and/or magnesium counterions to about 25% of the carboxylate groups on the polymer may be administered with base in an amount sufficient to provide about 0.5 equivalents of added base per equivalent of carboxylate groups in the polymer in the same or separate composition, formulation, or dosage form as the polymer. In another example, a disclosed polymer that contains calcium and/or magnesium counterions to about 25% of the carboxylate groups on the polymer may be administered with base in an amount sufficient to provide about 0.35 equivalents of added base per equivalent of carboxylate groups in the polymer.

[0077] In some embodiments, the base is one or more of: an alkali metal hydroxide, an alkali metal acetate, an alkali metal carbonate, an alkali metal bicarbonate, an alkali metal oxide, an alkaline earth metal hydroxide, an alkaline earth metal acetate, an alkaline earth metal carbonate, an alkaline earth metal bicarbonate, an alkaline earth metal oxide, and an organic base. In some embodiments, the base is choline, lysine, arginine, histidine, a pharmaceutically acceptable salt thereof, or a combination thereof. In some embodiments, the base is an acetate, a butyrate, a propionate, a lactate, a succinate, a citrate, an isocitrate, a fumarate, a malate, a malonate, an oxaloacetate, a pyruvate, a phosphate, a carbonate, a bicarbonate, a lactate, a benzoate, a sulfate, a lactate, a silicate, an oxide, an oxalate, a hydroxide, an amine, a dihydrogen citrate, or a combination thereof. In some embodiments, the base is a bicarbonate, a carbonate, an oxide, or a hydrochloride. In related embodiments, the base is one or more of: calcium bicarbonate, calcium carbonate, calcium oxide, and calcium hydroxide. In some embodiments, the base is a lithium salt, a sodium salt, a potassium salt, a magnesium salt, a calcium salt, an aluminum salt, a rubidium salt, a barium salt, a chromium salt, a manganese salt, an iron salt, a cobalt salt, a nickel salt, a copper salt, a zinc salt, an ammonium salt, a lanthanum salt, a choline salt, or a serine salt of any of the foregoing anions or anion combinations.

[0078] In some embodiments, the base may be selected to avoid increasing a level of a particular cation associated with the subject. For example, a method of treatment for hyperkalemia in a subject would preferably include administering a base that does not include potassium cations, in conjunction with a polymer or composition, formulation or dosage form containing a polymer as disclosed herein. Similarly, a composition according to the present disclosure intended to treat hypernatremia in a subject would preferably contain a base that does not include sodium cations

[0079] In some embodiments, the base may be selected to specifically increase the amount of a particular cation important in the disease or condition of the subject. For example, a method of treatment for hyponatremia, for example, in a subject suffering simultaneously from hyperkalemia and hyponatremia, would preferably contain a base that either includes sodium cations or alters the polymer binding in such a manner that fewer sodium cations are removed by the polymer.

[0080] In some embodiments, the disclosed polymers and compositions, formulations, and/or dosage forms containing the polymers described herein have superior manufacturing and processing properties in comparison to analogous polymers, compositions, formulations, and/or dosage forms wherein the carboxylate groups of the polymer are bound to hydrogen cations (e.g., protons; H⁺) instead of calcium cations at the levels described herein. Typically, polymers with predominantly unneutralized carboxylate groups (e.g., more than about 95% of the carboxylates are bound to hydrogen cations) are very adhesive, which may result in manufacturing difficulties and poor oral delivery or mucoadhesive properties. For example, certain methods for preparing the disclosed polymers, compositions, formulations, and/or dosage forms require transferring the polymer from one vessel to another, drying the polymer, grinding or milling to form a powder, filtering the polymer, etc. The adhesive properties associated with polymer having predominantly unneutralized carboxylate groups may render one these exemplary processes difficult, time- consuming, cost-inefficient, or sub-optimal for scale up.

[0081] Generally speaking, processing of polycarboxylate polymers, handling of carboxylate polymer, and oral delivery properties of polycarboxylate polymers improve with increasing levels of bound non-hydrogen cations, e.g., calcium ions and/or magnesium ions. For example, polymers disclosed herein have about calcium and/or magnesium counterions to about 5% to about 30% of the carboxylate groups in the polymer. Such polymers are characterized by dramatically improved manufacturability due to greatly reduced adhesive properties. In addition, the adhesive properties associated with polymers having predominantly unneutralized carboxylate groups lead to poor oral delivery properties as they generally hydrate rapidly when exposed to saliva, becoming bioadhesive. The hydrated form of the polymer causes the material to adhere to oral tissue, including teeth, which can lead to irritation. In contrast, polymers disclosed herein, which have calcium and/or magnesium counterionsn to about 5% to about 30% of the carboxylate groups in the polymer, possess improved oral delivery properties.

[0082] Additionally, generally speaking, processing of polycarboxylate polymers, handling of carboxylate polymer, and oral delivery properties of polycarboxylate polymers improve with increasing levels of bound non-hydrogen cations, e.g., calcium ions and/or magnesium ions. For example, polymers disclosed herein have about calcium and/or magnesium counterions to about 15% to about 35% of the carboxylate groups in the polymer. Such polymers are characterized by dramatically improved manufacturability due to greatly reduced adhesive properties. In addition, the adhesive properties associated with polymers having predominantly unneutralized carboxylate groups lead to poor oral delivery properties as they generally hydrate rapidly when exposed to saliva, becoming bioadhesive. The hydrated form of the polymer causes the material to adhere to oral tissue, including teeth, which can lead to irritation. In contrast, polymers disclosed herein, which have calcium and/or magnesium counterionsn to about 15% to about 35% of the carboxylate groups in the polymer, possess improved oral delivery properties.

[0083] In some embodiments, a polymer and/or composition of the present disclosure has an in vitro saline absorption capacity {e.g., saline holding capacity) of greater than or at least about 20 times its own weight {e.g., greater than or at least about 20 grams of saline per gram of composition, or "g/g")- In related embodiments, the polymer and/or composition has an in vitro saline absorption capacity {e.g., saline holding capacity) of about 20 times, about 25 times, about 30 times, about 35 times, about 40 times, about 45 times, about 50 times, about 55 times, about 60 times, about 65 times, about 70 times, about 75 times, about 80 times, about 85 times, about 90 times, about 95 times, or about 100 times its own weight, or more. Measurement of the in vitro saline holding capacity of the polymers and compositions according to the present disclosure may be accomplished by any method known in the art, for example, methods as described in Examples 8 and 9.

[0084] In one embodiment, a crosslinked cation-binding polymer comprising monomers {e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[0085] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 10% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 10%> (designated for purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base.

[0086] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[0087] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 20%> (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[0088] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[0089] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[0090] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[0091] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[0092] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[0093] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[0094] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[0095] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[0096] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[0097] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[0098] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[0099] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00100] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00101] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20% (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00102] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00103] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00104] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 10% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 10% (designated for purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base.

[00105] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[00106] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00107] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00108] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00109] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10% (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[00110] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 20%> (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00111] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00112] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00113] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 20%> (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00114] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00115] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00116] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00117] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00118] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00119] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00120] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00121] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 4% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00122] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00123] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 10% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 10%> (designated for purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base.

[00124] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[00125] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 20%> (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00126] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00127] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00128] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[00129] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10% (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00130] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00131] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00132] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00133] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00134] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00135] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00136] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00137] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00138] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00139] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20% (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00140] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 3% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00141] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00142] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 10% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 10%> (designated for purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base.

[00143] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[00144] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00145] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00146] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00147] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[00148] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 20%> (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00149] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10% (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00150] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00151] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00152] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00153] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00154] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20% (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00155] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00156] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00157] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00158] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20% (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00159] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 2% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00160] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00161] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 10% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 10% (designated for purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base.

[00162] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[00163] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00164] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00165] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 5% (designated for the purpose of calculation as 0.05 equivalents), the amount of added base is about 0.90 equivalents base and with calcium and/or magnesium counterions to about 30%> (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00166] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 15% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 15% (designated for purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base.

[00167] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 20%> (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00168] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10%> (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00169] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 10% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 10% (designated for the purpose of calculation as 0.10 equivalents), the amount of added base is about 0.85 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00170] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 20% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 20% (designated for purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base.

[00171] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00172] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00173] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 25% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 25% (designated for purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base.

[00174] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20% (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00175] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g., acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 30% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 30% (designated for purpose of calculation as 0.30 equivalents), the amount of added base is about 0.65 equivalents base.

[00176] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 15% (designated for the purpose of calculation as 0.15 equivalents), the amount of added base is about 0.80 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00177] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 20% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 20%> (designated for the purpose of calculation as 0.20 equivalents), the amount of added base is about 0.75 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00178] In one embodiment, a crosslinked cation-binding polymer comprising monomers (e.g. , acrylic acid) comprising carboxylate groups is a crosslinked polyacrylate, wherein said polymer contains calcium and/or magnesium cations that are counterions to about 25% to about 35% of the carboxylate groups of said polymer, and wherein the polymer comprises no more than about 1% sodium cations as counterions to the carboxylate groups of said polymer. In some embodiments, compositions, formulations and/or dosage forms may comprise such a polymer and a base, wherein the sum of the calcium and/or magnesium counterions and the added base is an amount up to a total of about 0.95 equivalents of carboxylic acid groups of the polymer. For example, with calcium and/or magnesium counterions to about 25% (designated for the purpose of calculation as 0.25 equivalents), the amount of added base is about 0.70 equivalents base and with calcium and/or magnesium counterions to about 35% (designated for purpose of calculation as 0.35 equivalents), the amount of added base is about 0.6 equivalents base.

[00179] The present disclosure also relates to methods of using the polymers, and compositions, formulations, and/or dosage forms containing the polymers disclosed herein, with or without added base, to treat various diseases and disorders, ion imbalances, and fluid imbalances. [00180] In some embodiments, the disease or disorder is one or more of: heart failure, a renal insufficiency disease, end stage renal disease, liver cirrhosis, chronic renal insufficiency, chronic kidney disease, fluid overload, fluid maldistribution, edema, pulmonary edema, peripheral edema, lymphedema, nephrotic edema, idiopathic edema, ascites, cirrhotic ascites, interdialytic weight gain, high blood pressure, hyperkalemia, hypernatremia, abnormally high total body sodium, hypercalcemia, tumor lysis syndrome, head trauma, an adrenal disease, hyporeninemic hypoaldosteronism, hypertension, salt- sensitive hypertension, refractory hypertension, renal tubular disease, rhabdomyolysis, crush injuries, renal failure, acute tubular necrosis, insulin insufficiency, hyperkalemic periodic paralysis, hemolysis, malignant hyperthermia, pulmonary edema secondary to cardiogenic pathophysiology, pulmonary edema with non-cardiogenic origin, drowning, acute glomerulonephritis, allergic pulmonary edema, high altitude sickness, Adult Respiratory Distress Syndrome, traumatic edema, cardiogenic edema, acute hemorrhagic edema, heatstroke edema, facial edema, eyelid edema, angioedema, cerebral edema, scleral edema, nephritis, nephrosis, nephrotic syndrome, glomerulonephritis, and/or renal vein thrombosis.

[00181] In some embodiments, the disease or disorder is the result of, or is associated with, administration of another drug. For example, compositions and/or dosage forms as disclosed herein are useful in treating an increase in a subject's potassium level when co- administered with a drug known to cause increases in potassium levels. In some embodiments, such a drug is an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist, etc.

Preparation of Crosslinked Cation-Binding Polymers

[00182] Crosslinked cation-binding polymers, including, for example, polyelectrolyte polymers, such as polyacrylate polymers, etc., may be prepared by methods known in the art, including by suspension methods, aqueous one-phase methods {e.g., Buchholz, F. L. and Graham, A. T., "Modern Superabsorbent Polymer Technology," John Wiley & Sons (1998)) and by precipitation polymerization {see, e.g., European Patent Application No. EP0459373A2). Polymers with differential properties may be prepared that are useful as therapeutics for different diseases and disorders, including those involving an ion imbalance and/or a fluid imbalance. For example, methods are provided for washing the cross-linked polymer with an acid to replace bound counterions other than hydrogen with hydrogen. The polymeric material, including for example polymeric beads, may be further processed by milling or grinding the polymeric material into particles. A polymer as described herein may contain many carboxylic acid groups, for example, polyacrylic acid, which may be reacted with alkali metals to produce a polycarboxylate, for example, polyacrylate. Many of these polycarboxylates act as superabsorbent polymers and have a saline absorption capacity (e.g., saline holding capacity) of over twenty times their mass in vitro (e.g., about 40 times its mass) as measured in 0.9% saline solution (e.g., 0.15 M sodium chloride solution) buffered to pH 7 (see, e.g., Examples 5 and 6). Exemplary methods are provided below.

1. Manufacture of Crosslinked Cation-Binding Polymers

[00183] Cross-linked cation-binding polymers, including cross-linked polyacrylate and/or polyacrylic acid polymers, may be prepared by commonly known methods in the art. In an exemplary method, cross-linked polyelectrolyte polymers may be prepared as a suspension of drops of aqueous solution in a hydrocarbon, for example, a liquid hydrocarbon (e.g., by inverse suspension polymerization).

[00184] Cross-linked polyacrylate polymers may be prepared by polymerization of partially neutralized acrylic acid in an aqueous environment where an appropriate cross- linker is present in small quantities. Given that there is an inverse relationship between the amount of fluid the polymer will absorb and the degree of cross-linking of the polymer, it may be desirable to have a low level of cross-linking to obtain a fluid absorption capacity of at least 20 g/g (e.g. 20 g/g, 30 g/g, 40 g/g, 50 g/g, 60 g/g, 70 g/g, 80 g/g, 90 g/g, or 100 g/g polymer), for use in methods as described herein. However, there is also an inverse relationship between the degree of cross-linking and the percentage of polymer chains that do not cross-link. Non-crosslinked polymer is soluble and may not contribute to the absorbency of the polymer since it dissolves in the fluid. For example, polyacrylates can be designed to absorb about 35 times their mass in pH 7 buffered physiological saline as a compromise between high absorbency and minimal soluble polymer.

[00185] Since the amount of reactants used in a polymerization reaction varies depending upon the size of the reactor and other factors, the precise amount of each reactant used in the preparation of cross-linked polyelectrolyte polymer, such as polyacrylate, may be determined by one of skill in the art. For example, in a five-hundred gallon reactor, about 190 to 200 pounds (roughly 85 to 90 kg) of acrylic acid may be used while in a three liter reactor 150 to 180 g of acrylic acid may be used. Accordingly, the amount of each reactant used for the preparation of an exemplary cross-linked polyacrylate may be expressed as a weight ratio to acrylic acid. Thus, acrylic acid weight may be taken as 1.0000 and other compounds are represented in relation to this value. Exemplary amounts of reactants used for the preparation of such a cross-linked polyacrylate by an inverse suspension polymerization are presented in Table 1.

[00186] Table 1 : Exemplary amounts of reactants in an inverse suspension polymerization Substance Low value High Value

Acrylic acid 1.0000 1.0000

Water 0.5000 3.0000

Hydrophobic solvent 1.2000 12.0000

Base (expressed as 50% NaOH) 0.6600 (60% neutral) 1.1 100 (100% neutralized) Crosslinker 0.0030 0.0080

Initiator 0.0005 0.0200

Chelating agent 0.0000 0.0050

Surfactant 0.0050 0.0400

[00187] An exemplary inverse suspension reaction to form a crosslinked polymer may involve preparation of two mixtures (e.g., a hydrophobic mixture and an aqueous mixture) in two different vessels followed by combination of the mixtures to form a reaction mixture. One vessel may be designated as a hydrophobic compound vessel and the other may be designated as an aqueous solution vessel. The hydrophobic compounds may be mixed in a larger vessel that will become a reaction vessel, while an aqueous solution may be prepared in a smaller vessel that may be discharged into the reaction vessel. In an exemplary embodiment, the hydrophobic mixture may contain solvent, surfactant, and crosslinking agent, and the aqueous mixture may contain water, base, monomer (e.g., acrylic acid), initiator, and optional chelating agent.

[00188] A hydrophobic solvent may be introduced into the reaction vessel. As will be appreciated by one of skill in the art, a hydrophobic solvent (also referred to herein as the "oil phase") may be chosen based upon one or more considerations, including, for example, the density and viscosity of the oil phase, the solubility of water in the oil phase, the partitioning of the neutralized and unneutralized ethylenically unsaturated monomers between the oil phase and the aqueous phase, the partitioning of the crosslinker and the initiator between the oil phase and the aqueous phase and/or the boiling point of the oil phase.

[00189] Hydrophobic solvents contemplated for use in the present disclosure include, for example, Isopar™ L (isoparaffm fluid), toluene, benzene, dodecane, cyclohexane, n- heptane and/or cumene. Preferably, Isopar™ L is chosen as a hydrophobic solvent due to its low viscosity, high boiling point and low solubility for neutralized monomers such as sodium acrylate and/or potassium acrylate. One of skill in the art will appreciate that a large enough volume of hydrophobic solvent is used to ensure that the aqueous phase is suspended as droplets in the oil rather than the reverse and that the aqueous phase droplets are sufficiently separated to prevent coalescence into large masses of aqueous phase.

[00190] One or more surfactants and one or more cross-linkers may be added to the oil (hydrophobic) phase. The oil phase may then be agitated and sparged with an inert gas, such as nitrogen or argon to remove oxygen from the oil phase. It will be appreciated that the amount of surfactant used in the reaction depends on the size of the desired polymer particles and the agitator stir rate. This addition of surfactant is designed to coat the water droplets formed in the initial reaction mixture before the reaction starts. Higher amounts of surfactant and higher agitation rates produce smaller droplets with more total surface area. It will be understood by those of skill in the art that an appropriate choice of cross-linker and initiator may be used to prepare spherical to ellipsoid shaped beads. One of skill in the art will be capable of determining an appropriate cross-linker for the preparation of a specified cross-linked cation-binding polymer. For example, cross-linker choice depends on whether it needs to be hydrophobic or hydrophilic polymer or whether it needs to resist acidic or basic external conditions. An amount of cross-linker depends on how much soluble polymer is permissible and how much saline holding capacity is desired.

[00191] Exemplary surfactants include hydrophobic agents that are solids at room temperature, including, for example, hydrophobic silicas (such as Aerosil® or Perform-O- Sil™) and glycolipids (such as polyethylene glycol distearate, polyethylene glycol dioleate, sorbitan monostearate, sorbitan monooleate or octyl glucoside).

[00192] Crosslinking agents with two or more vinyl groups, each group of which is independently polymerizable, may be used, allowing for a wide variety in molecular weight, aqueous solubility and/or lipid (e.g., oil) solubility. Crosslinking agents contemplated for use in the present disclosure, include, for example, diethyleneglycol diacrylate, diacryl glycerol, triallylamine, tetraallyloxy ethane, allylmethacrylate, 1,1,1-trimethylolpropane triacrylate (TMPTA), divinyl benzene and divinyl glycol.

[00193] In some embodiments, the crosslinker is one or more compounds having (in one molecule) 2-4 groups selected from the group consisting of CH₂=CHCO-, CH=C(CH₃)CO- and CH₂=CH-CH₂-, for example and without limitation: diacrylates and dimethacrylates of ethylene glycol, glycerol, diethylene glycol, triethylene glycol, tetraethyleneglycol, propylene glycol, dipropyleneglycol, tripropyleneglycol, tetrapropyleneglycol, polyoxyethylene glycols and polyoxypropylene glycols, 1,4- butanediol, 1,5-pentanediol, 1,6-hexanediol, neopentyl glycol, trimethylol propane, and pentaerythritol; triacrylates and trimethacrylates of trimethylolpropane and pentaerythritol; highly ethoxylated trimethylol propane triacrylate; tetracrylate and tetramethacrylate of pentaerythritol; allyl methacrylate, triallylamine, triallylcitrate and tetraallyloxy ethane.

[00194] In some embodiments, a heat activated crosslinker may be used in the preparation of crosslinked polymers according to the present disclosure. Non- limiting examples of heat-activated crosslinkers include hydroxyl-containing crosslinking agents, amine- containing crosslinking agents, or epoxy-containing crosslinking agents containing at least one functionality suitable to react with a carboxyl group on the polymer and containing at least two functional groups capable of forming covalent bonds with the polymer. Some non- limiting examples of heat-activated crosslinkers suitable for such use is the class of compounds commonly referred to as polyols or polyhydroxy compounds. Some non- limiting examples of polyols include: glycerin, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, 1 ,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, neopentyl glycol, polyglycerin, trimethylolpropane, polyethylene glycol, and polypropylene glycol-polyethylene glycol copolymers. Masked polyols, such as ethyleneglycol diacetate may also be used. Some non-limiting examples of heat-activated crosslinkers containing amine functionality are ethylenediamine, diethylenetriamine, triethylenetetramine, monoethanolamine, and aminoethylethanolamine. Some non-limiting examples of heat- activated crosslinkers containing epoxy functionality are glycidyl acrylate, glycidylmethacrylate, and ethyleneglycol diglycidylether,

[00195] In some embodiments, dimodal crosslinkers may be used in the preparation of crosslinked polymers according to the present disclosure. Dimodal crosslinkers contain one or more carboxylic acid-reactive groups and one or more ethylenically unsaturated groups in the same compound. Non-limiting examples of dimodal crosslinkers suitable for use to crosslink polymers according to the present disclosure include: 2- hydroxyethyl(meth)acrylate, polyethylene glycol monomethacrylate, glycidyl methacrylate, allyl glycidyl ether, hydroxypropyl methacrylate, hydroxyethyl methacrylate, and hexapropylene glycol monomethacrylate.

[00196] In some embodiments, polyvinyl compounds may be used in the preparation of crosslinked polymers according to the present disclosure. Non-limiting examples of polyvinyl crosslinkers include divinyl compounds or polyvinyl compounds such as: divinyl glycol, divinyl benzene, divinyl toluene, divinyl xylene, divinyl ether, divinyl ketone, trivinyl benzene; unsaturated polyesters that can be obtained by reacting an unsaturated acid such as maleic acid with polyols such as: ethylene glycol, glycerol, diethylene glycol, triethylene glycol, tetraethyleneglycol, propylene glycol, dipropyleneglycol, tripropyleneglycol, tetrapropyleneglycol, polyoxyethylene glycols and polyoxypropylene glycols, 1 ,4-butanediol, 1,5-pentanediol, 1 ,6-hexanediol, neopentyl glycol, trimethylol propane, and pentaerythritol; diesters or polyesters of unsaturated mono-or polycarboxylic acids with polyols derived from reaction of C₂-Cio polyhydric alcohols with 2-8 C₂-C₄ alkylene oxide units per hydroxyl group, such as tri methylol propane hexaethoxyl triacrylate; di-methacrylic acid or tri-methacrylic acid esters that can be obtained by reacting polyepoxide with methacrylic acid; bis(meth)acrylamides such as N,N-methylene- bisacrylamide; carbamyl esters that can be obtained by reacting polyisocyanates, such as tolylene diisocyanate, hexamethylene diisocyanate, 4,4'-diphenyl methane diisocyanate; and NCO-containing prepolymers obtained by reacting such diisocyanates with active hydrogen atom-containing compounds with hydroxyl group-containing monomers, such as di- methacrylic acid carbamyl esters obtainable by reacting the above-mentioned diisocyanates with hydroxyethyl(meth)acrylate; di(meth)allyl ethers or poly(meth)allyl ethers of polyols such as alkylene glycols, glycerol, polyalkylene glycols, polyoxyalkylene polyols and carbohydrates such as polyethylene glycol diallyl ether, allylated starch, and allylated cellulose; di-allyl or poly-allyl esters of polycarboxylic acids, such as diallyl phthalate and diallyl adipate; and esters of unsaturated monocarboxylic acids or polycarboxylic acids with mono(meth)allyl ester of polyols, such as allyl methacrylate or (meth)acrylic acid ester of polyethylene glycol monoallyl ether.

[00197] In some embodiments, the crosslinker may be one or more compound consistent with the following formula:

R¹-(-(R²0)„-C(0)R³)_x , wherein:

R¹ is a straight-chain or branched-chain Ci-Cio polyalkoxy radical, optionally substituted with one or more oxygen atoms in the backbone, having x valences;

each R² is independently a C₂-C4 alkylene group;

each R³ is independently a straight-chain or branched-chain C₂-C₁₀ alkenyl moiety;

n is a positive integer from 1-20; and

x is a positive integer from 2-8.

[00198] An aqueous phase mixture may be prepared in another vessel {e.g., a vessel that is separate from that used to prepare the hydrophobic phase) that contains water. For example, preparation of neutralized or partially neutralized polymer, base and monomer are added to the water. For preparation of non-neutralized (acid form) polymer, monomer is added to the water without base. It will be appreciated by one of skill in the art that the amount of base used in the vessel is determined by the degree of neutralization of the monomer desired. For neutralized or partially neutralized polymer, a degree of neutralization between about 60% and 100% is preferred. Without wishing to be bound by a theory or mechanism, it is believed that one -hundred percent neutralization minimizes the chance of suspension failure, but the highly charged monomer may not react as rapidly and may not pull hydrophobic crosslinkers into the forming polymer. Considerations in choosing the degree of neutralization may be determined by one of skill in the art and include, for example, the effect of monomer charge {e.g., as determined by ionization of the cation from the neutralized molecules) on reaction rate, partitioning of the monomer and neutralized monomer between oil phase and aqueous phase and/or tendency of the aqueous droplets to coalesce during the reaction. The solubilities of sodium acrylate and sodium methacrylate in water are limited and are lower at lower temperatures {e.g., sodium acrylate is soluble at about 45% at 70 °C but less than 40% at 20 °C). This solubility may establish the lower limit of the amount of water needed in the neutralization step. The upper limit of the amount of water may be based on reactor size, amount of oil phase needed to reliably suspend the aqueous phase as droplets and/or the desired amount of polymer produced per batch.

[00199] Bases contemplated for use in methods of making the crosslinked polymers of the present disclosure include, for example, hydroxides, bicarbonates, or carbonates. Use of these bases allows neutralization of the acid monomer without residual anions left in the reaction mixture as the anions react to form water or C0₂. Frequently, sodium bases are chosen in the method of making the crosslinked polymers. However, potassium bases, ammonium bases, and bases of other cations, including calcium bases, are contemplated for use in the present disclosure.

[00200] The water used in the reaction may be purified water or water from other sources such as city water or well water. If the water used is not purified water, chelating agents may be needed to control metals, e.g., heavy metal ions, such as iron, calcium, and/or magnesium from destroying the initiator. Chelating agents contemplated for use with the present disclosure include, for example, diethylenetriaminepentaacetic acid pentasodium (Versenex™ 80). The amount of chelating agent added to the reaction mixture may be determined by one of skill in the art from a determination of the amount of undesirable metal in the water.

[00201] In some instances a metal may be added to catalyze the polymerization reaction (e.g., iron).

[00202] Once base is added to the water, the aqueous phase solution may be cooled to remove the heat released from dilution of the base, and one or more classes of monomers may be added, to react with the base, for example, monomers which will be neutralized by the base. As will be appreciated by one of skill in the art, the monomers will be neutralized to the degree dictated by the amount of base in the reaction. The aqueous phase solution may be kept cool (e.g., below 35 to 40 °C) and preferably around 20 °C to prevent formation of prepolymer strands, dimers and/or possible premature polymerization.

[00203] Monomers are dissolved in water at concentrations of 10-70 wt% or 20-40 wt% and polymerization may subsequently be initiated by free radicals in the aqueous phase. Monomers may be polymerized either in the acid form or as a partially neutralized salt. For an inverse suspension process, monomers in the acid form may be less desirable due to high solubility in the oil phase. The amount of water used to dissolve the monomer is minimally set so that all of the monomer (e.g., sodium acrylate) is dissolved in the water rather than crystallizing and maximally set so that there is the smallest volume of reaction mixture possible (to minimize the amount of distillation and allow the maximum yield per batch).

[00204] Exemplary monomer units contemplated for use in the present disclosure, include, for example, acrylic acid and its salts, methacrylic acid and its salts, crotonic acid and its salts, tiglinic acid and its salts, 2-methyl-2-butenoic acid (Z) and its salts, 3-butenoic acid (vinylacetic acid) and its salts, 1-cyclopentene carboxylic acid, and 2-cyclopentene carboxylic acid and their salts; and unsaturated dicarboxylic acids and their salts, such as maleic acid, fumaric acid, itaconic acid, glutaconic acid, and their salts. Other cross-linked polyelectrolyte superabsorbent polymers may be based on sulfonic acids and their salts, or phosphonic acids and their salts. In other non-limiting embodiments, additional monomers may be contemplated for use. The additional monomers are those from which the desired carboxylic acid, sulfonic acid, or phosphonic acid functionality may be derived by known chemical reactions, for example by hydrolysis. In these embodiments, the monomer, for example, acrylonitrile, acrylamide, methacrylamide, lower alcohol esters of unsaturated, polymerizable carboxylic acids (such as those mentioned in the paragraph above) or their mixtures, and the like may be polymerized with a suitable crosslinker to an intermediate crosslinked polymer, which is then subjected to chemical reaction (so-called "polymer analogous reaction") to convert the functional groups of the polymer into carboxylic functionality. For example, ethyl acrylate may be polymerized with a non-hydrolysis- susceptible crosslinker (e.g. tetraallyloxyethane) to form a crosslinked intermediate polymer, which is then subjected to hydrolysis conditions to convert the ester functionality to carboxylic acid functionality by means known in the art. In another example, acrylonitrile is graft polymerized to starch with a crosslinker as necessary to form a crosslinked starch- graft intermediate polymer, which is then treated with aqueous base to hydrolyze the nitrile functionality to carboxylic acid functionality (see, e.g., U.S. Patent Nos. 3,935,099, 3,991,100, 3,997,484, and 4,134,863).

[00205] One or more initiators, such as free radical producers, may be added to the aqueous phase just before the aqueous phase is transferred into the oil phase. As will be appreciated by one of skill in the art, the initiator amount and type used in the polymerization reaction depends on oil versus water solubility and whether longer chain lengths are desired. For example, a lower amount of initiator may be used in the polymerization reaction when longer chain lengths are desired.

[00206] In some embodiments, one of the initiators may be a thermally sensitive compound such as a persulfate, 2,2'-azobis(2-amidino-propane)-dihydrochloride, 2,2'- azobis (2-amidino-propane)-dihydrochloride and/or 2,2'-azobis (4-cyanopentanoic acid). With thermally sensitive initiators polymerization does not begin until an elevated temperature is reached. For persulfates, this temperature is approximately 50 to 55 °C. Since the reaction is highly exothermic, vigorous removal of the heat of reaction is required to prevent boiling of the aqueous phase. It is preferred that the reaction mixture be maintained at approximately 65 °C. As will be appreciated by one of skill in the art, thermal initiators have the advantage of allowing control of the start of the reaction when the reaction mixture is adequately sparged of oxygen.

[00207] In some embodiments, one of the initiators may be a redox pair such as persulfate/bisulfate, persulfate/thiosulfate, persulfate/ascorbate, hydrogen peroxide/ascorbate, sulfur dioxide/tert-butylhydroperoxide, persulfate/erythorbate, tert- butylhydroperoxide/erythorbate and/or tert-butylperbenzoate/erythorbate. These initiators are able to initiate the reaction at room temperature, thereby minimizing the chance of heating the reaction mixture to the boiling point of the aqueous phase as heat is removed through the jacket around the reactor.

[00208] In some embodiments, the reaction is not started immediately after the mixing of the aqueous phase into the oil phase in the final reactor because the aqueous phase still has an excessive amount of oxygen dissolved in the water. It will be appreciated by one of skill in the art that an excessive amount of oxygen may cause poor reactivity and inadequate mixing may prevent the establishment of uniform droplet sizes. Instead, the final reaction mixture is first sparged with an inert gas for ten to sixty minutes after all reagents (except the redox pair if that initiator system is used) have been placed in the reactor. The reaction may be initiated when a low oxygen content (e.g., below 15 ppm) is measured in the inert gas exiting the reactor.

[00209] It will be appreciated by those of skill in the art that with acrylate and methacrylate monomers, polymerization begins in the droplets and progresses to a point where coalescence of the particles becomes more likely (the "sticky phase"). It may be necessary that a second addition of surfactant (e.g., appropriately degassed to remove oxygen) be added during this phase or that the agitation rate be increased. For persulfate thermal initiation, this sticky phase may occur at about 50 to 55 °C. For redox initiation systems, the need for additional surfactant may be lessened by the initial surface polymerization, but if additional surfactant is needed, it should be added as soon as an exotherm is noted.

[00210] The reaction may be continued for four to six hours after the peak exotherm is seen to allow for maximal consumption of the monomer into the polymer. Following the reaction, the polymeric material may be isolated by either transferring the entire reaction mixture to a centrifuge or filter to remove the fluids or by initially distilling the water and some of the oil phase (e.g., frequently as an azeotrope) until no further removal of water is possible and the distillation temperature rises significantly above 100 °C, followed by isolating the polymeric material by either centrifugation or filtering. The isolated crosslinked cation-binding polymeric material is then dried to a desired residual moisture content (e.g., less than 5%).

[00211] An exemplary cross-linked cation-binding polymer, polyacrylate, may be formed by copolymerizing an ethylenically unsaturated carboxylic acid with a multifunctional cross-linking monomer. The acid monomer or polymer may be substantially or partially neutralized with an alkali metal salt such as an oxide, a hydroxide, a carbonate, or a bicarbonate and polymerized by the addition of an initiator. One such exemplary polymer gel is a copolymer of acrylic acid/sodium acrylate and any of a variety of cross-linkers.

[00212] The reactants for the synthesis of an exemplary cross-linked cation-binding polymer, cross-linked polyacrylate, is provided in Table 2 below. This cross-linked cation- binding polymer may be produced as a one -hundred kilogram batch in a five-hundred gallon vessel.

Table 2: List of Components Used in the Manufacture of an Exemplary Cross-linked Polyacrylate Polymer

[00213] In addition to inverse (water-in-oil) suspension methods, cation-binding polymers may be prepared by other methods known in the art (e.g., Buchholz, F. L. and Graham, A. T., "Modern Superabsorbent Polymer Technology," John Wiley & Sons (1998)), for example by aqueous one-phase methods, by precipitation polymerization (see, e.g., European Patent Application No. EP0459373A2), and by crosslinking of soluble polymer using monomers, crosslinkers, surfactants, initiators, neutralizing agents, solvents, suspending agents, and chelators as described herein. For example, cation-binding polymers containing carboxyl groups formed from monomers as described herein may be polymerized to form soluble polymer which may then be crosslinked. In some embodiments, it may be possible to incorporate the crosslinker either into the intermediate polymer, or into the chemically-reacted carboxylic acid functional polymer. For example, crosslinker may be incorporated by copolymerization of the contemplated monomers with a crosslinker as described herein, and then the crosslinked polymer may be converted by, for example hydrolysis, to the desired crosslinked carboxylic acid-functional product. Alternatively, the contemplated additional monomers may be polymerized to a non- crosslinked polymer, then converted to the carboxylic acid-functional polymer and subsequently reacted with a suitable crosslinker (for example, one of the heat-activated crosslinkers in the list) to provide the desired, crosslinked, carboxylic acid-functional polymer. Because it is difficult to thoroughly mix a small amount of crosslinker into a high molecular weight polymer, it is desirable to add a heat-activated crosslinker to the monomer-containing reaction mixture, under conditions in which the crosslinker is inactive toward reaction. The polymerization is accomplished in the normal way to yield an uncrosslinked polymer that also contains the molecularly dispersed, heat-activated crosslinker. When it is desired to form the crosslinks, the polymer system is heated to a temperature that is suitable to cause the reaction between polymer functional groups and the crosslinker molecules, thereby crosslinking the polymer. 2. Preparation of Crosslinked Cation-Binding Polymers with Hydrogen Counterions from Neutralized or Partially Neutralized Crosslinked Cation-Binding Polymers

[00214] Partially neutralized or fully neutralized crosslinked cation-binding polymers may be acidified by washing the polymer with acid. Suitable acids contemplated for use with the present disclosure, include, for example, hydrochloric acid, acetic acid and phosphoric acid.

[00215] Those skilled in the art will recognize that the replacement of the counterions, including cations such as sodium atoms, by hydrogen atoms can be performed with many different acids and different concentrations of acid. However, care must be taken in choice of acid and concentration to avoid damage to the polymer or the cross-linkers. For instance, nitric and sulfuric acids would be avoided.

[00216] Acid- washed crosslinked cation-binding polymers may be additionally rinsed with water and then dried in, for example, a vacuum oven or inert atmosphere until, for example, less than 5% moisture remains, to produce a substantially free acid form of cross- linked polyacrylic acid. Any particle form of partially or fully neutralized cross-linked cation-binding polymer may be used as the starting point, for example, particles, powders, or bead-form particles, or milled bead- form particles. 3. Preparation of Crosslinked Cation-Binding Polymers with Hydrogen Counterions

[00217] Acid form cross-linked cation-binding polymers may be prepared by any method known by those skilled in the art (e.g., Buchholz, F. L. and Graham, A. T., "Modern Superabsorbent Polymer Technology," John Wiley & Sons (1998)), for example by inverse suspension, aqueous one -phase polymerization, by precipitation polymerization (see, e.g., European Patent Application No. EP0459373A2), and by crosslinking of soluble polymer. Any of the methods, monomers, crosslinkers, surfactants, initiators, neutralizing agents, solvents, suspending agents, chelators, catalysts, and other agents as described herein may be used.

[00218] Crosslinked cation-binding polymers may be prepared from monomers with unneutralized carboxylic acid groups. For example, a crosslinked polyacrylate can be prepared from acrylic acid. A monomer solution is prepared in a reactor by dissolving an unsaturated carboxylic acid monomer (e.g., acrylic acid) in water. Optionally, a chelating agent (e.g., Versenex™ 80) may be added to control metal ions and/or a metal added to catalyze the polymerization reaction (e.g., iron). A suitable crosslinking agent (e.g., trimethylolpropane triacrylate) is added to the reactor. The solution may be agitated and oxygen may be removed using nitrogen, argon or by other means known in the art. The temperature of the solution may be adjusted as desired. One or more polymerization initiators may be added to the reactor and the oxygen tension may be reduced or the temperature may be increased to initiate polymerization. The reaction is allowed to proceed through the exothermic heating that occurs during reaction. Reaction heat can be removed and/or controlled as desired by methods known to those skilled in the art. The reaction vessel may then be heated and oxygen tension in the reaction vessel may be kept low to continue the polymerization to low levels of residual monomer. Once the reaction is completed, the polymerization reaction product can be removed from the reactor and the wet polymer may be reduced in size (e.g. by cutting or by methods known to those skilled in the art) into pieces of appropriate size for drying. The polymer pieces can then be dried in a vacuum oven or other equipment known to those skilled in the art. Conditions during drying may be adjusted (e.g. humidity level, rate of drying) so that polymerization and reduction of residual monomer continues during the drying process. After drying, the particles can be separated by size and/or milled and/or sieved to produce the desired particle size. Other examples of the polymerization of aqueous acrylic acid solutions with crosslinkers are disclosed in Buchholz, F. L. and Graham, A. T., "Modern Superabsorbent Polymer Technology," John Wiley & Sons (1998), U.S. Patent No. 4,654,039; U.S. Patent No. 4,295,987; U.S. Patent No. 5,145,906; and U.S. Patent No. 4,861 ,849, the contents of which are incorporated herein by reference.

4. Preparation of Crosslinked Cation-Binding Polymers with Calcium and/or Magnesium Counterions

[00219] Crosslinked, cation-binding polymers with calcium and/or magnesium ions may be prepared by ion-exchange from a partially neutralized crosslinked, cation-binding polymer, by the addition of a calcium and/or magnesium base to an acid form of a crosslinked, cation-binding polymer, by using a calcium or magnesium base to neutralize acrylic acid prior to polymerization, or by other methods known by those skilled in the art. Any particle form of partially or fully neutralized cross-linked cation-binding polymer may be used as the starting point, for example, particles, powders, or bead-form particles, or milled bead-form particles.

[00220] Partially neutralized crosslinked cation-binding polymers (e.g. sodium acrylate) may be hydrated and equilibrated with several washes of a salt solution of calcium and/or magnesium (e.g. CaCl₂, MgCl₂) of a concentration high enough to exchange the original counterions on the polymer with the calcium and/or magnesium cations and remove the original counterions from the solution. For polymer more highly neutralized than the desired calcium or magnesium polymer, an appropriate amount of acid may be added with the calcium and/or magnesium salt to bring the neutralization level down to the desired level. Those skilled in the art will recognize that the replacement of the counterions (ion- exchange), including cations such as sodium atoms, by calcium and/or magnesium cations can be performed with many different calcium and/or magnesium salts and salt concentrations. The calcium and/or magnesium crosslinked cation-binding polymers may be additionally rinsed with water and then dried in, for example, a vacuum oven or inert atmosphere until, for example, less than 5% moisture remains.

[00221] Crosslinked cation-binding polymers with calcium and/or magnesium counterions may be produced from the acid form of the polymer through the addition of a calcium and/or magnesium base (e.g, CaC0₃, MgO). The base may be added to the polymer as a solid or solution and the polymer may be hydrated prior to addition of the base. The polymer and base may be stirred and/or heated to facilitate neutralization of the polymer with the base. The calcium and/or magnesium crosslinked cation-binding polymers may be additionally rinsed with water and then dried in, for example, a vacuum oven or inert atmosphere until, for example, less than 5% moisture remains.

[00222] Crosslinked cation-binding polymers with calcium and magnesium counterions may be prepared from monomers with unneutralized carboxylic acid groups (acid form) and a calcium or magnesium base. A solution of the calcium or magnesium base is prepared by adding the appropriate base slowly to water (e.g. CaC0₃, MgO). Cooling may be used to control the solution temperature. The monomer solution is then prepared in a reactor by adding the monomer (e.g., acrylic acid), water and the base solution and then stirring. Alternatively, the solid base can be added to the reactor with the monomer and water. Care should be taken to ensure that the base does not precipitate. Optionally, a chelating agent (e.g., Versenex™ 80) may be added to control metal ions and/or a metal added to catalyze the polymerization reaction (e.g., iron). A suitable crosslinking agent (e.g., trimethylolpropane triacrylate) is added to the reactor and the mixture stirred. Oxygen may be removed using a nitrogen or argon sparge, or by other means known in the art. The temperature of the solution may be adjusted. One or more polymerization initiators (e.g. sodium persulfate) are added to the reactor and the reaction mixture is bubbled with an inert gas (e.g., nitrogen) and agitated until adequate removal of oxygen is achieved. The reaction is then initiated either by reaching an oxygen concentration where a redox couple (e.g., tertiary butylhydroperoxide/thiosulfate, or hydrogen peroxide/erythorbic acid) produces enough radicals that are not quenched by oxygen, or by adding heat to cause a temperature dependent initiator (e.g., sodium persulfate) to produce radicals. The reaction is allowed to proceed through the exothermic heating that occurs during reaction. Reaction heat can be removed and/or controlled as desired by methods known to those skilled in the art. The reaction vessel may then be heated and oxygen tension in the reaction vessel may be kept low to continue the polymerization to low levels of residual monomer. Once the reaction is completed, the polymerization reaction product can be removed from the reactor and the wet polymer may be reduced in size (e.g. by cutting or by methods known to those skilled in the art) into pieces of appropriate size for drying. The polymer pieces can then be dried in a vacuum oven or other equipment known to those skilled in the art. Conditions during drying may be adjusted (e.g. humidity level, rate of drying) so that polymerization and reduction of residual monomer continues during the drying process. After drying, the particles can be separated by size and/or milled and/or sieved to produce the desired particle size.

[00223] Exemplary crosslinked cation-binding polymers, including for example those prepared according to Examples 1-4, generally have a pH 7 buffered saline holding capacity of about 20 g/g or greater, including, for example, greater than about 40 g/g as described in Examples 5 and 6; and contain less than about 5,000 ppm of sodium, less than about 20 ppm of heavy metals, less than about 1000 ppm (e.g., less than about 500 ppm) of residual monomer, less than about 2,000 ppm of residual chloride, and less than about 20 wt % of soluble polymer. Preferably, acidified polymers useful as crosslinked cation-binding polymers prepared according to this disclosure have a saline holding capacity of preferably greater than about 40 g/g, (e.g., 80 g/g) contain less than about 500 ppm of sodium, less than about 20 ppm of heavy metals, less than about 500 ppm of residual monomer, less than about 1 ,500 ppm of residual chloride, and less than about 10 wt.% of soluble polymer.

[00224] Crosslinked cation-binding polymers prepared, for example, according to the method of Example 1 or 2 using acrylic acid monomers, followed by acidification as described in Example 3, or crosslinked cation-binding polymers prepared, for example, as described in Example 4, are referred to as "H-CLP" or "HCLP" in Examples 7 to 15.

[00225] The polymer particles may be reduced in size by milling or grinding or other means known to those skilled in the art. Particles of certain size ranges or a particle size distribution may be obtained by means known to those of skill in the art, for example, by sieving through sieves or screens. Seives may be stacked vertically starting with the smallest pore size at the bottom (largest mesh size) to largest pore size at the top (smallest mesh size). The material is placed on top of the screen and the screens are shaken to allow particles to pass through screens until they are caught on a screen smaller than diameter. The material on each screen will then be smaller than the screen above, but larger than the screen below. For example, particles that pass through an 18 Mesh screen and are caught on a 20 Mesh screen are between 850 and 1000 microns in diameter. Screen mesh and the corresponding maximum particle size allowed to pass through the mesh include, 18 mesh, 1000 microns; 20 mesh, 850 microns; 25 mesh, 710 microns; 30 mesh, 600 microns; 35 mesh, 500 microns, 40 mesh, 425 microns; 45 mesh, 35 microns; 50 mesh, 300 microns; 60 mesh, 250 microns; 70 mesh, 212 microns; 80 mesh, 180 microns; 100 mesh, 150 microns; 120 mesh, 125 microns; 140 mesh, 106 microns; 170 mesh, 90 microns; 200 mesh, 75 microns; 230 mesh, 63 microns; and 270 mesh, 53 microns. Thus particles of varying sizes may be obtained through the use of one or more screens.

[00226] The particle size range may be characterized, for example, by sieves or screens, a particle size distribution determined, for example, by laser light diffraction, by an average size, or other measures. A particles size distribution for material passing through a 35 mesh (500 um) screen but captured on a 70 mesh (210 um) screen may be characterized as the weight % of the polymer greater than 500 um, the fraction between 210 to 500 um, and the fraction below 210 um. In an exemplary polymer fraction collected using 35 and 70 mesh screens, the fraction between 210-500um would preferably be greater than 70%. The particle size distribution can also be characterized by describing particle diameters where 10% (Do.i), 50% (D0.5), or 90% (D0.9) of the particles are smaller than that particle size.

Compositions, Formulations, and Dosage Forms

[00227] Compositions, formulations, and/or dosage forms, e.g., pharmaceutical compositions, formulations, and/or dosage forms, are also disclosed comprising a cross- linked cation-binding polymer comprising monomers containing carboxylic acid groups {e.g., a cross-linked polyacrylic acid polymer) and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium cations are counterions to about 5% to about 30% of the carboxylic acid groups in the polymer (alternately, the polymer comprises calcium and/or magnesium counterions to about 5%> to about 10%>, about 5%> to about 15%), about 5%> to about 20%>, about 5%> to about 25%>, about 5%> to about 30%>, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in the polymer). In some embodiments, the polymer comprises calcium and/or magnesium cations that are counterions to about 5%>, about 10%>, about 15%>, about 20%>, about 25%), about 30%>, or about 35%> of the carboxylate groups in the polymer. In related embodiments, the calcium and/or magnesium cations are counterions to about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%), about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%), or about 30% of the carboxylate groups in the polymer. These polymers, compositions, formulations, and/or dosage forms may be delivered to a subject, including using a wide variety of routes or modes of administration. In some embodiments, the compositions, formulations, and/or dosage forms as disclosed herein optionally comprise an added base. Preferred routes for administration are oral or intestinal.

[00228] Compositions, formulations, and/or dosage forms, e.g., pharmaceutical compositions, formulations, and/or dosage forms, are also disclosed comprising a cross- linked cation-binding polymer comprising monomers containing carboxylic acid groups {e.g., a cross-linked polyacrylic acid polymer) and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium cations are counterions to about 15% to about 35% of the carboxylic acid groups in the polymer (alternately, the polymer comprises calcium and/or magnesium counterions to about 15% to about 20%, about 15% to about 25%), about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20%) to about 30%, about 20% to about 35%, about 25% to about 30%, or about 25% to about 35% of the carboxylate groups in the polymer). In some embodiments, the polymer comprises calcium and/or magnesium cations that are counterions to about 15%, about 20%), about 25%, about 30%, or about 35% of the carboxylate groups in the polymer. In related embodiments, the calcium and/or magnesium cations are counterions to about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%), about 31%), about 32%, about 33%, about 34%, or about 35% of the carboxylate groups in the polymer. These polymers, compositions, formulations, and/or dosage forms may be delivered to a subject, including using a wide variety of routes or modes of administration. Preferred routes for administration are oral or intestinal.

[00229] In some embodiments, a composition, formulation, or dosage form as disclosed herein comprises a polymer that comprises calcium cations as counterions to about 5% to about 30%) of the carboxylate groups on the polymer, and sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer. In such embodiments, the polymer further comprises hydrogen cations {e.g., protons) as counterions to all or substantially all of the carboxylate groups to which calcium and sodium are not counterions (e.g., "free carboxylates"), for example about 95% of the free carboxylates, about 96%> of the free carboxylates, about 97% of the free carboxylates, about 98% of the free carboxylates, about 99% of the free carboxylates, about 99.5% of the free carboxylates, or about 100% of the free carboxylates. In some embodiments, the polymer comprises calcium cations as counterions to about 25% of the carboxylate groups on the polymer, sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to all or substantially all of the free carboxylates.

[00230] In some embodiments, a composition, formulation, or dosage form as disclosed herein comprises a polymer that comprises calcium cations as counterions to about 15% to about 35%) of the carboxylate groups on the polymer, and sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer. In such embodiments, the polymer further comprises hydrogen cations (e.g., protons) as counterions to all or substantially all of the carboxylate groups to which calcium and sodium are not counterions (e.g., "free carboxylates"), for example about 95% of the free carboxylates, about 96%> of the free carboxylates, about 97% of the free carboxylates, about 98% of the free carboxylates, about 99% of the free carboxylates, about 99.5% of the free carboxylates, or about 100% of the free carboxylates. In some embodiments, the polymer comprises calcium cations as counterions to about 25% of the carboxylate groups on the polymer, sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to all or substantially all of the free carboxylates.

[00231] In some embodiments, a composition, formulation, or dosage form as disclosed herein comprises a polymer that comprises magnesium cations as counterions to about 5% to about 30%) of the carboxylate groups on the polymer and sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and further comprises hydrogen cations (e.g., protons) as counterions to all or substantially all of the carboxylate groups to which magnesium or sodium are not counterions (e.g., "free carboxylates"), for example about 95% of the free carboxylates, about 96% of the free carboxylates, about 97% of the free carboxylates, about 98% of the free carboxylates, about 99% of the free carboxylates, about 99.5% of the free carboxylates, or about 100% of the free carboxylates. In some embodiments, the polymer comprises calcium cations as counterions to about 25% of the carboxylate groups on the polymer, sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to all or substantially all of the free carboxylates.

[00232] In some embodiments, a composition, formulation, or dosage form as disclosed herein comprises a polymer that comprises magnesium cations as counterions to about 15% to about 35%) of the carboxylate groups on the polymer and sodium cations as counterions to no more than about 5% of the carboxylate groups on the polymer, and further comprises hydrogen cations (e.g., protons) as counterions to all or substantially all of the carboxylate groups to which magnesium or sodium are not counterions (e.g., "free carboxylates"), for example about 95% of the free carboxylates, about 96% of the free carboxylates, about 97% of the free carboxylates, about 98% of the free carboxylates, about 99% of the free carboxylates, about 99.5% of the free carboxylates, or about 100% of the free carboxylates. In some embodiments, the polymer comprises calcium cations as counterions to about 25% of the carboxylate groups on the polymer, sodium cations as counterions to no more than about 5%> of the carboxylate groups on the polymer, and hydrogen cations (e.g., protons) as counterions to all or substantially all of the free carboxylates.

[00233] In some embodiments, a composition, formulation, or dosage form as described herein comprises a crosslinked cation-binding polymer comprising repeat units containing carboxylic acid groups, and wherein the polymer further comprises calcium and/or magnesium cations that are counterions to about 5% to about 30% of the carboxylate groups in the polymer (alternatively, to about 5% to about 10%, about 5% to about 15%, about 5% to about 20%), about 5% to about 25%, about 5% to about 30%>, about 10%> to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in the polymer) and further comprises an added base, wherein the base is present in an amount sufficient to provide up to about 0.9 equivalents of base per equivalent of carboxylic acid groups in the polymer. In a related example the composition, formulation, or dosage form contains about 0.05 equivalents, about 0.1 equivalents, about 0.15 equivalents, about 0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about 0.35 equivalents, about 0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.55 equivalents, about 0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75 equivalents, about 0.8 equivalents, about 0.85 equivalents, or about 0.9 equivalents of base per equivalent of carboxylic acid groups in the polymer.

[00234] In some embodiments, a composition, formulation, or dosage form as described herein comprises a crosslinked cation-binding polymer comprising repeat units containing carboxylic acid groups, and wherein the polymer further comprises calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, to about 15% to about 20%, about 15% to about 25%, about 15%) to about 30%>, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%), about 20% to about 35%, about 25% to about 30%, or about 25% to about 35% of the carboxylate groups in the polymer) and further comprises an added base, wherein the base is present in an amount sufficient to provide up to about 0.8 equivalents of base per equivalent of carboxylic acid groups in the polymer. In a related example the composition, formulation, or dosage form contains about 0.05 equivalents, about 0.1 equivalents, about 0.15 equivalents, about 0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about 0.35 equivalents, about 0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.55 equivalents, about 0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75 equivalents, or about 0.8 equivalents of base per equivalent of carboxylic acid groups in the polymer.

[00235] In some embodiments, a composition, formulation, and/or dosage form as described herein comprises a crosslinked cation-binding polymer comprising carboxylic acid-containingmonomers and calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are present in an amount sufficient to act as counterions to about 5%> to about 30%) of the carboxylate groups in the polymer, and an amount of added base sufficient to provide up to about 0.9 equivalents of base per equivalent of carboxylate groups in the polymer (alternatively, about 0.2 to about 0.9, about 0.3 to about 0.6, or about 0.35 to about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer; alternatively, the base is present in an amount sufficient to provide about 0.65 to about 0.75, such as about 0.66, about 0.70, about 0.73, about 0.74 equivalents of base per equivalent of carboxylate groups in the polymer). In related embodiments, the calcium and/or magnesium cations are present in an amount sufficient to act as counterions to about 15% to about 30%) of the carboxylate groups in the polymer, and added base is present in an amount sufficient to provide up to about 0.9 equivalents of base per equivalent of carboxylate groups in the polymer (alternatively, about 0.3 to about 0.6 or about 0.35 to about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer). In related embodiments, the calcium and/or magnesium cations are present in an amount sufficient to act as counterions to about 20% to about 30% of the carboxylate groups in the polymer, and added base is present in an amount sufficient to provide up to about 0.75 equivalents of base per equivalent of carboxylate groups in the polymer (alternatively, about 0.2 to about 0.75, 0.3 to about 0.6 or about 0.35 to about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer).

[00236] In some embodiments, a composition, formulation, and/or dosage form as described herein comprises a crosslinked cation-binding polymer comprising carboxylic acid-containingmonomers and calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are present in an amount sufficient to act as counterions to about 15%) to about 35%) of the carboxylate groups in the polymer, and an amount of added base sufficient to provide up to about 0.8 equivalents of base per equivalent of carboxylate groups in the polymer (alternatively, about 0.2 to about 0.8, about 0.3 to about 0.6, or about 0.35 to about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer; alternatively, the base is present in an amount sufficient to provide about 0.65 to about 0.75, such as about 0.66, about 0.70, about 0.73, about 0.74 equivalents of base per equivalent of carboxylate groups in the polymer). In related embodiments, the calcium and/or magnesium cations are present in an amount sufficient to act as counterions to about 15% to about 30% of the carboxylate groups in the polymer, and added base is present in an amount sufficient to provide up to about 0.8 equivalents of base per equivalent of carboxylate groups in the polymer (alternatively, about 0.3 to about 0.6 or about 0.35 to about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer). In related embodiments, the calcium and/or magnesium cations are present in an amount sufficient to act as counterions to about 20% to about 30% of the carboxylate groups in the polymer, and added base is present in an amount sufficient to provide up to about 0.75 equivalents of base per equivalent of carboxylate groups in the polymer (alternatively, about 0.2 to about 0.75, 0.3 to about 0.6 or about 0.35 to about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer). In related embodiments, the calcium and/or magnesium cations are present in an amount sufficient to act as counterions to about 25% to about 35% of the carboxylate groups in the polymer, and added base is present in an amount sufficient to provide up to about 0.7 equivalents of base per equivalent of carboxylate groups in the polymer (alternatively, about 0.2 to about 0.7, about 0.3 to about 0.6, or about 0.35 to about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer).

[00237] The polymers in any of the compositions, formulations, and/or dosage forms disclosed herein may comprise sodium cations which (if present) are counterions to no more than about 5%, 4%, 3%, 2%, 1%, or 0.5% of the carboxylate groups in the polymer.

[00238] In some embodiments, the polymers disclosed herein for inclusion in a composition, formulation, or dosage form, e.g., for administration to an individual, e.g., for use in methods of treatment disclosed herein, are individual particles or particles agglomerated to form a larger particle (for example, flocculated particles), and have a diameter of about 1 to about 10,000 microns (alternatively, about 1 micron to about 50 microns, about 10 microns to about 50 microns, about 10 microns to about 200 microns, about 50 microns to about 100 microns, about 50 microns to about 200 microns, about 50 microns to about 1000 microns, about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or about 5000 microns to about 10,000 microns). In some embodiments, the particles or agglomerated particles have a diameter of about 1, about 5, about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, about 150, about 160, about 170, about 180, about 190, about 200, about 250, about 300, about 350, about 400, about 450, about 500, about 550, about 600, about 650, about 700, about 750, about 800, about 850, about 900, about 950, about 1000 , about 1500, about 2000, about 2500, about 3000, about 3500, about 4000, about 4500, about 5000, about 5500, about 6000, about 7000, about 7500, about 8000, about 8500, about 9000, about 9500, or about 10,000 microns.

[00239] In some embodiments, the crosslinked cation-binding polymer disclosed herein for inclusion in a composition, formulation, or dosage form, e.g., for administration to an individual, e.g., for use in methods of treatment disclosed herein is a crosslinked polyacrylate polymer. For example, the polymer may be a polyacrylate polymer crosslinked with about 0.08 mol% to about 0.2 mol% crosslinker or alternatively from about 0.025 mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.% to about 0.3 mol.%., and for example, may comprise an in vitro saline absorption capacity {e.g., saline holding capacity) of at least about 20 times its weight (e.g., at least about 20 grams of saline per gram of polymer, or "g/g"), at least about 30 times its weight, at least about 40 times its weight, at least about 50 times its weight, at least about 60 times its weight, at least about 70 times its weight, at least about 80 times its weight, at least about 90 times its weight, at least about 100 times its weight, or more. In some embodiments, the crosslinked polyacrylate polymer is in the form of individual particles or particles that are agglomerated (for example, flocculated) to form a larger particle, wherein the diameter of individual particles or agglomerated particles is about 1 micron to about 10,000 microns (alternatively, about 1 micron to about 10 microns, about 1 micron to about 50 microns, about 10 microns to about 50 microns, about 10 microns to about 200 microns, about 50 microns to about 100 microns, about 50 microns to about 200 microns, about 50 microns to about 1000 microns, about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or about 5000 microns to about 10,000 microns. In one embodiment, the polyacrylate polymer is in the form of small particles that flocculate to form agglomerated particles with a diameter of about 1 micron to about 10 microns.

[00240] In some embodiments in which a composition, formulation, or dosage form comprises an optionally added base, the optionally added base component is one or more of: an alkali metal hydroxide, an alkali metal acetate, an alkali metal carbonate, an alkali metal bicarbonate, an alkali metal oxide, an alkali earth metal hydroxide, an alkali earth metal acetate, an alkali earth metal carbonate, an alkali earth metal bicarbonate, an alkali earth metal oxide, an organic base, choline, lysine, arginine, histidine, an acetate, a butyrate, a propionate, a lactate, a succinate, a citrate, an isocitrate, a fumarate, a malate, a malonate, an oxaloacetate, a pyruvate, a phosphate, a carbonate, a bicarbonate, a lactate, a benzoate, a sulfate, a lactate, a silicate, an oxide, an oxalate, a hydroxide, an amine, a dihydrogen citrate, calcium bicarbonate, calcium carbonate, calcium oxide, calcium hydroxide, magnesium oxide, magnesium carbonate, magnesium hydrochloride, sodium bicarbonate, and potassium citrate, or a combination thereof. In one embodiment, the added base is calcium carbonate.

[00241] In some embodiments, a composition, formulation, or dosage form disclosed herein comprises a polyacrylate polymer that comprises calcium and/or magnesium counterions to about 5% to about 30% of the carboxylate groups in the polymer, for example, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%), about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%o, about 28%, about 29%, or about 30% of the carboxylate groups in the polymer, and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polyacrylate polymer. In some embodiments, the composition, formulation, or dosage form additionally comprises added base, for example, calcium carbonate base, present in an amount to provide up to about 0.8 equivalents of base per carboxylate group on the polyacrylate polymer, for example, about 0.05 equivalents, 0.1 equivalents, 0.15 equivalents, 0.2 equivalents, 0.25 equivalents, 0.3 equivalents, 0.35 equivalents, 0.4 equivalents, 0.45 equivalents, 0.5 equivalents, 0.55 equivalents, 0.6 equivalents, 0.65 equivalents, 0.7 equivalents, 0.75 equivalents, 0.8 equivalents, 0.85 equivalents, or 0.9 equivalents of base per equivalent of carboxylate groups in the polyacrylate polymer.

[00242] In some embodiments, a composition, formulation, or dosage form disclosed herein comprises a polyacrylate polymer that comprises calcium and/or magnesium counterions to about 15% to about 35% of the carboxylate groups in the polymer, for example, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%), about 30%, about 31%, about 32%, about 33%, about 34%, or about 35% of the carboxylate groups in the polymer, and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polyacrylate polymer. In some embodiments, the composition, formulation, or dosage form additionally comprises added base, for example, calcium carbonate base, present in an amount to provide up to about 0.8 equivalents of base per carboxylate group on the polyacrylate polymer, for example, about 0.05 equivalents, 0.1 equivalents, 0.15 equivalents, 0.2 equivalents, 0.25 equivalents, 0.3 equivalents, 0.35 equivalents, 0.4 equivalents, 0.45 equivalents, 0.5 equivalents, 0.55 equivalents, 0.6 equivalents, 0.65 equivalents, 0.7 equivalents, 0.75 equivalents, or 0.8 equivalents of base per equivalent of carboxylate groups in the polyacrylate polymer.

[00243] In some embodiments, the above compositions, formulations, and/or dosage forms additionally comprise one or more excipients, carriers, or diluents. Compositions for use in accordance with the present disclosure may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the polymer into preparations which may be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. Such compositions may contain a therapeutically effective amount of polymer and may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers include those approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly, in humans. Carriers can include an active ingredient in which the disclosed compositions are administered.

[00244] In some embodiments, the dosage form is a capsule, a tablet, a chewable tablet, a suspension, an oral suspension, a powder, a gel block, a gel pack, a confection, a chocolate bar, a pudding, a flavored bar, or a sachet. In some embodiments, the dosage form contains about 0.25 g, 0.5 g, or 1 g to about 7.5 g, 15 g, 30 g, or about 100 g of a disclosed cation- binding polymer. For example and without limitation, the composition, formulation, or dosage form may include about 0.25 g, about 0.5 g, about 1 g, about 1.5 g, about 2 g, about 2.5 g, about 3 g, about 3.5 g, about 4 g, about 4.5 g, about 5 g, about 5.5 g, about 6 g, about 6.5 g, about 7 g, about 7.5 g, about 8 g, about 8.5 g, about 9 g, about 9.5 g, about 10 g, about 11 g, about 12 g, about 13 g, about 14 g, about 15 g, about 16 g, about 17 g, about 18 g, about 19 g, about 20 g, about 21 g, about 22 g, about 23 g, about 24 g, about 25 g, about 26 g, about 27 g, about 28 g, about 29 g, about 30 g , about 35 g, about 40 g, about 45 g, about 50 g, about 55 g, about 60 g, about 65 g, about 70 g, about 75 g, about 80 g, about 85 g, about 90 g, about 95 g, or about 100 g, or more of the cation-binding polymer. Regardless of the amount of polymer present in the dosage form, the dosage forms of the present disclosure may optionally also include up to about 0.9 equivalents of base, for example, a pharmaceutically and/or physiologically acceptable base, per equivalent of carboxylate groups in the polymer, for example, about 0.05 equivalents, about 0.1 equivalents, about 0.15 equivalents, 0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about 0.35 equivalents, about 0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.55 equivalents, about 0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75 equivalents, about 0.8 equivalents, about 0.85 equivalents, or about 0.9 equivalents of base per equivalent of carboxylic acid groups in the polymer. In some embodiments, the base is present in an amount sufficient to provide from about 0.2 equivalents to about 0.8 equivalents of base, for example about 0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about 0.35 equivalents, about 0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.55 equivalents, about 0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75 equivalents, about 0.8 equivalents, about 0.85 equivalents, or about 0.9 equivalents of base per equivalent of carboxylate groups in the polymer. In other embodiments, the base is present in an amount sufficient to provide from about 0.3 equivalents to about 0.6 equivalents of base, for example about 0.3 equivalents, about 0.35 equivalents, about or 0.4 equivalents of base, about 0.45 equivalents of base, about 0.5 equivalents of base, about 0.55 equivalents of base, or about 0.6 equivalents of base per equivalent of carboxylate groups in the polymer. In some embodiments, the base is present in an amount sufficient to provide about 0.5 equivalents of base per equivalent of carboxylate groups in the polymer.

[00245] For oral administration, the disclosed polymers and/or compositions may be formulated readily by combining them with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compositions of the disclosure to be formulated, as tablets, chewable tablets, pills, dragees, capsules, liquids, gel packs, gel blocks, syrups, slurries, suspensions, wafers, sachets, powders, dissolving tablets and the like, for oral ingestion by a subject, including a subject to be treated. In some embodiments, the compositions have a coating. In some embodiments, the compositions or capsules containing the compositions have an enteric coating. In other embodiments, the compositions or capsules containing the disclosed polymers do not have an enteric coating.

[00246] In some embodiments, a composition, formulation, and/or dosage form as described herein comprises a base and a crosslinked polycarboxylate polymer as described herein (e.g., a cross-linked polyacrylic acid polymer), wherein the polymer further comprises calcium cations, wherein the calcium cations are counterions to about 5% to about 30% of the carboxylic acid groups in the polymer (alternately, counterions to about about 5%) to about 10%>, about 5% to about 15%, about 5% to about 20%>, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%o, about 15%) to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in the polymer), and is administered in an amount sufficient to provide from about 0.01 moles of carboxylate groups to about 0.5 moles or about 1.4 moles of carboxylate groups to the subject per day, for example, about 0.01 moles, about 0.02 moles, about 0.03 moles, about 0.04 moles, about 0.05 moles, about 0.06 moles, about 0.07 moles, about 0.08 moles, about 0.09 moles, about 0.1 moles, about 0.1 1 moles, about 0.12 moles, about 0.13 moles, about 0.14 moles, about 0.15 moles, about 0.16 moles, about 0.17 moles, about 0.18 moles, about 0.19 moles, about 0.2 moles, about 0.21 moles, about 0.22 moles, about 0.23 moles, about 0.24 moles, about 0.25 moles, about 0.26 moles, about 0.27 moles, about 0.28 moles, about 0.29 moles, about 0.3 moles, about 0.31 moles, about 0.32 moles, about 0.33 moles, about 0.34 moles, about 0.35 moles, about 0.36 moles, about 0.37 moles, about 0.38 moles, about 0.39 moles, about 0.4 moles, about 0.41 moles, about 0.42 moles, about 0.43 moles, about 0.44 moles, about 0.45 moles, about 0.46 moles, about 0.47 moles, about 0.48 moles, about 0.49 moles, about 0.5 moles, about 0.6 moles, about 0.7 moles, about 0.8 moles, about 0.9 moles, about 1.0 moles, about 1.1 moles, about 1.2 moles, about 1.3 moles, or about 1.4 moles of carboxylate groups to the subject per day. In a preferred embodiment, the dosage forms are administered in an amount sufficient to provide from about 0.01 to about 0.25 moles of carboxylate groups per day. In a more preferred embodiment, the dosage forms are administered in an amount sufficient to provide from about 0.1 to about 0.25 moles of carboxylate groups per day.

[00247] In some embodiments, a composition, formulation, and/or dosage form as described herein comprises a base and a crosslinked polycarboxylate polymer as described herein (e.g., a cross-linked polyacrylic acid polymer), wherein the polymer further comprises calcium cations, wherein the calcium cations are counterions to about 15% to about 35% of the carboxylic acid groups in the polymer (alternately, counterions to about 15%) to about 20%o, about 15%> to about 25%>, about 15%> to about 30%>, about 15%> to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25%o to about 30%>, or about 25%> to about 35%>, of the carboxylate groups in the polymer), and is administered in an amount sufficient to provide from about 0.01 moles of carboxylate groups to about 0.5 moles or about 1.4 moles of carboxylate groups to the subject per day, for example, about 0.01 moles, about 0.02 moles, about 0.03 moles, about 0.04 moles, about 0.05 moles, about 0.06 moles, about 0.07 moles, about 0.08 moles, about 0.09 moles, about 0.1 moles, about 0.1 1 moles, about 0.12 moles, about 0.13 moles, about 0.14 moles, about 0.15 moles, about 0.16 moles, about 0.17 moles, about 0.18 moles, about 0.19 moles, about 0.2 moles, about 0.21 moles, about 0.22 moles, about 0.23 moles, about 0.24 moles, about 0.25 moles, about 0.26 moles, about 0.27 moles, about 0.28 moles, about 0.29 moles, about 0.3 moles, about 0.31 moles, about 0.32 moles, about 0.33 moles, about 0.34 moles, about 0.35 moles, about 0.36 moles, about 0.37 moles, about 0.38 moles, about 0.39 moles, about 0.4 moles, about 0.41 moles, about 0.42 moles, about 0.43 moles, about 0.44 moles, about 0.45 moles, about 0.46 moles, about 0.47 moles, about 0.48 moles, about 0.49 moles, about 0.5 moles, about 0.6 moles, about 0.7 moles, about 0.8 moles, about 0.9 moles, about 1.0 moles, about 1.1 moles, about 1.2 moles, about 1.3 moles, or about 1.4 moles of carboxylate groups to the subject per day. In a preferred embodiment, the dosage forms are administered in an amount sufficient to provide from about 0.01 to about 0.25 moles of carboxylate groups per day. In a more preferred embodiment, the dosage forms are administered in an amount sufficient to provide from about 0.1 to about 0.25 moles of carboxylate groups per day.

[00248] In some embodiments, the dosage form comprises a base and a crosslinked polycarboxylate polymer as described herein, (e.g., a cross-linked polyacrylic acid polymer), wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylic acid groups in the polymer (alternately, counterions to about 5% to about 10%), about 5%> to about 15%, about 5% to about 20%>, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in the polymer), and is administered in an amount sufficient to provide from about 1 g to about 30 g or about 1 g or up to about 100 g or more of polymer per day, for example, about 1 g per day, about 2 g per day, about 3 g per day, about 4 g per day, about 5 g per day, about 6 g per day, about 7 g per day, about 8 g per day, about 9 g per day, about 10 g per day, about 1 1 g per day, about 12 g per day, about 13 g per day, about 14 g per day, about 15 g per day, about 16 g per day, about 17 g per day, about 18 g per day, about 19 g per day, about 20 g per day, about 21 g per day, about 22 g per day, about 23 g per day, about 24 g per day, about 25 g per day, about 26 g per day, about 27 g per day, about 28 g per day, about 29 g per day, about 30 g per day, about 35 g per day, about 40 g per day, about 45 g per day, about 50 g per day, about 55 g per day, about 60 g per day, about 65 g per day, about 70 g per day, about 75 g per day, about 80 g per day, about 85 g per day, about 90 g per day, about 95 g per day, or about 100 g of polymer per day or more.

[00249] In some embodiments, the dosage form comprises a base and a crosslinked polycarboxylate polymer as described herein, (e.g., a cross-linked polyacrylic acid polymer), wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylic acid groups in the polymer (alternately, counterions to about 15% to about 20%), about 15%) to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25% to about 30%), or about 25% to about 35% of the carboxylate groups in the polymer), and is administered in an amount sufficient to provide from about 1 g to about 30 g or about 1 g or up to about 100 g or more of polymer per day, for example, about 1 g per day, about 2 g per day, about 3 g per day, about 4 g per day, about 5 g per day, about 6 g per day, about 7 g per day, about 8 g per day, about 9 g per day, about 10 g per day, about 11 g per day, about 12 g per day, about 13 g per day, about 14 g per day, about 15 g per day, about 16 g per day, about 17 g per day, about 18 g per day, about 19 g per day, about 20 g per day, about 21 g per day, about 22 g per day, about 23 g per day, about 24 g per day, about 25 g per day, about 26 g per day, about 27 g per day, about 28 g per day, about 29 g per day, about 30 g per day, about 35 g per day, about 40 g per day, about 45 g per day, about 50 g per day, about 55 g per day, about 60 g per day, about 65 g per day, about 70 g per day, about 75 g per day, about 80 g per day, about 85 g per day, about 90 g per day, about 95 g per day, or about 100 g of polymer per day or more.

[00250] In some embodiments, the dosage form is a sachet and contains a polymer or polymer-containing composition according to the present disclosure in sufficient amount to provide from about 1 g to about 30 g of the polymer. For example, a sachet may contain a composition according to the present disclosure in sufficient amount to provide about 1 g, about 1.5 g, about 2 g, about 2.5 g, about 3 g, about 3.5 g, about 4 g, about 4.5 g, about 5 g, about 5.5 g, about 6 g, about 6.5 g, about 7 g, about 7.5 g, about 8 g, about 8.5 g, about 9 g, about 9.5 g, about 10 g, about 10.5 g, about 11 g, about 11.5 g, about 12 g, about 12.5 g, about 13 g, about 13.5 g, about 14 g, about 14.5 g, about 15 g, about 15.5 g, about 16 g, about 16.5 g, about 17 g, about 17.5 g, about 18 g, about 18.5 g, about 19 g, about 19.5 g, about 20 g, about 20.5 g, about 21 g, about 21.5 g, about 22 g, about 22.5 g, about 23 g, about 23.5 g, about 24 g, about 24.5 g, about 25 g, about 25.5 g, about 26 g, about 26.5 g, about 27 g, about 27.5 g, about 28 g, about 28.5 g, about 29 g, about 29.5 g, or about 30 g of polymer.

[00251] In some embodiments, the dosage form is a capsule containing an amount of a polymer or polymer-containing composition according to the present disclosure sufficient to provide from about 0.1 g to about 1 g of the polymer. For example, a capsule may contain an amount of a composition according to the present disclosure that is sufficient to provide about 0.1 g, about 0.15 g, about 0.2 g, about 0.25 g, about 0.3 g, about 0.35 g, about 0.4 g, about 0.45 g, about 0.5 g, about 0.55 g, about 0.6 g, about 0.65 g, about 0.7 g, about 0.75 g, about 0.8 g, about 0.85 g, about 0.9 g, about 0.95 g, or about 1 g of polymer.

[00252] In some embodiments, the dosage form is a tablet that contains an amount of a polymer or polymer-containing composition according to the present disclosure to provide from about 0.3 g to about 1 g or 2 g of the polymer. For example, the tablet may contain about 0.3 g, about 0.35 g, about 0.4 g, about 0.45 g, about 0.5 g, about 0.55 g, about 0.6 g, about 0.65 g, about 0.7 g, about 0.75 g, about 0.8 g, about 0.85 g, about 0.9 g, about 0.95 g, or about 1 g or 2 g of polymer. In some embodiment, a disclosed composition is formulated as a tablet that is spherical or substantially spherical.

[00253] In some embodiments, the dosage form is a sachet, flavored bar, gel block, gel pack, pudding, or powder that contains an amount of a polymer or polymer-containing composition according to the present disclosure to provide from about 1 g to about 30 g of the polymer. For example, the sachet, flavored bar, gel block, gel pack, pudding, or powder may contain an amount of a composition according to the present disclosure to provide about 2 g, about 3 g, about 4 g, about 5 g, about 6 g, about 7 g, about 8 g, about 9 g, about 10 g, about 11 g, about 12 g, about 13 g, about 14 g, about 15 g, about 16 g, about 17 g, about 18 g, about 19 g, about 20 g, about 21 g, about 22 g, about 23 g, about 24 g, about 25 g, about 26 g, about 27 g, about 28 g, about 29 g, or about 30 g of the polymer.

[00254] In some embodiments, the dosage form is a suspension or an oral suspension that contains an amount of a polymer or polymer-containing composition according to the present disclosure to provide from about 1 g to about 30 g of the polymer. For example, the suspension or oral suspension may contain an amount of a composition according to the present disclosure to provide about 2 g, about 3 g, about 4 g, about 5 g, about 6 g, about 7 g, about 8 g, about 9 g, about 10 g, about 11 g, about 12 g, about 13 g, about 14 g, about 15 g, about 16 g, about 17 g, about 18 g, about 19 g, about 20 g, about 21 g, about 22 g, about 23 g, about 24 g, about 25 g, about 26 g, about 27 g, about 28 g, about 29 g, or about 30 g of the polymer.

[00255] In some embodiments, compositions, formulations, and/or dosage forms according to the present disclosure further include an additional agent. In related embodiments, the additional agent is one that causes, routinely causes, typically causes, is known to cause, or is suspected of causing an increase in an ion level or total body fluid (e.g., edema) in at least some subjects upon administration. For example and without limitation, the additional agent may be an agent known to cause an increase in serum potassium levels in at least some subjects upon administration. For example and without limitation, the additional agent may be an agent known to cause an increase in serum sodium levels in at least some subjects upon administration. In related embodiments, the additional agent may be one or more of: a tertiary amine, spironolactone, fluoxetine, pyridinium and its derivatives, metoprolol, quinine, loperamide, chlorpheniramine, chlorpromazine, ephedrine, amitryptyline, imipramine, loxapine, cinnarizine, amiodarone, nortriptyline, a mineralocorticosteroid, propofol, digitalis, fluoride, succinylcholine, eplerenone, an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist, benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, candesartan, eprosartan, irbesartan, losartan, valsartan, telmisartan, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, nadolol, propranolol, sotalol, timolol, canrenone, aliskiren, aldosterone synthesis inhibitors, VAP antagonists, amiloride, triamterine, a potassium supplement, heparin, a low molecular weight heparin, a non-steroidal anti- inflammatory drug, ketoconazole, trimethoprim, pentamide, a potassium sparing diuretic, amiloride, and/or triamterene. In some embodiments, the additional agent may cause fluid retention and/or maldistribution in at least some subjects upon administration.

[00256] The polymer, compositions, formulations, and/or dosage forms of the present disclosure may be administered in combination with other therapeutic agents. The choice of therapeutic agents that may be co-administered with the compositions of the disclosure will depend, in part, on the condition being treated.

[00257] Polymers, compositions, formulations, and/or dosage forms of the present disclosure may be administered in combination with a therapeutic agent that causes an increase, or is known to commonly cause an increase, in one or more ions in the subject. By way of example only, the crosslinked cation-binding polymer of the present disclosure may be administered with a therapeutic agent that causes an increase, or is known to commonly cause an increase, in the potassium and/or sodium level of a subject.

Therapeutic Uses

[00258] The disclosed polymers, and compositions, formulations, and/or dosage forms comprising the disclosed polymers may be useful for therapeutic use, including to treat a subject with a disease and/or disorder, for example, to ameliorate, alleviate, or eliminate at least one symptom of the disease or disorder. Additionally or alternatively, the disclosed polymers, compositions comprising the disclosed polymers and/or dosage forms comprising the disclosed polymers may be used prophylactically to prevent a subject from becoming afflicted with a disease and/or disorder. In any of the methods of treatment or prophylaxis described herein, a base may be co-administered along with the polymer, or composition, formulation and/or dosage form comprising the polymer, either simultaneously or sequentially (e.g., before or after administration of the polymer). When administering the polymer in a dosage form, the base may be included in the same dosage form or separate from the dosage form containing the polymer, for example in a separate dosage form which is co-administered at the same time or before or after the dosage form that contains the polymer.

[00259] In some embodiments, polymers as disclosed herein, and/or compositions, formulations, and/or dosage forms containing the polymers, may be used in methods to treat congestive heart failure (CHF), chronic kidney disease (CKD), end stage renal disease (ESRD), hyperkalemia, hypernatremia, or hypertension.

[00260] In some embodiments, polymers as disclosed herein, and/or compositions, formulations, and/or dosage forms containing the polymers, may be used in methods for the removal of fluid from a subject.

[00261] In some embodiments, the polymers as disclosed herein, and/or compositions, formulations, and/or dosage forms containing the polymers, may be used in methods to treat or prevent fluid accumulation and/or maldistribution, and/or ion (e.g., sodium and/or potassium) accumulation and/or imbalances.

[00262] In some embodiments, polymers as disclosed herein, and/or compositions, formulations, and/or dosage forms containing the polymers, may be used in methods for treating diseases or disorders associated with increased retention of fluid and/or ion imbalances.

[00263] The polymers as disclosed herein, and/or compositions, formulations, and/or dosage forms containing the polymers, may be used to remove one or more ions selected from the group consisting of: sodium, potassium, calcium, magnesium, and/or ammonium.

[00264] Surprisingly, the polymers of the present disclosure, and compositions, formulations, and dosage forms of the present disclosure that comprise crosslinked cation- binding polymers comprising monomers containing carboxylic acid groups (e.g., polyacrylate polymers) and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 5%o to about 10%>, about 5% to about 15%, about 5% to about 20%>, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%o, about 15%o to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25% to about 30%> of the carboxylate groups in the polymer, or any of about 5%, about 10%), about 15%o, about 20%>, about 25%, or about 30%> of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, are optimized for maintaining the cation binding and/or removal properties of the polymer (e.g., for potassium and sodium) and/or the fluid binding and/or removal properties of the polymer in humans, while, in some embodiments, minimizing or eliminating changes in acid/base status (e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject.. As such, the polymers and compositions, formulations, and/or dosage forms containing the polymers as described herein are useful for the treatment of a variety of diseases or disorders, including those involving ion (e.g., potassium and/or sodium) and/or fluid imbalances (e.g., overloads).

[00265] Also, surprisingly, the polymers of the present disclosure, and compositions, formulations, and dosage forms of the present disclosure that comprise crosslinked cation- binding polymers comprising monomers containing carboxylic acid groups (e.g., polyacrylate polymers) and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 15%) to about 20%>, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25%o to about 30%, or about 25% to about 35% of the carboxylate groups in the polymer, or any of about 15%, about 20%, about 25%, about 30%, or about 35% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, are optimized for maintaining the cation binding and/or removal properties of the polymer (e.g., for potassium and sodium) and/or the fluid binding and/or removal properties of the polymer in humans, while, in some embodiments, minimizing or eliminating changes in acid/base status (e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. As such, the polymers and compositions, formulations, and/or dosage forms containing the polymers as described herein are useful for the treatment of a variety of diseases or disorders, including those involving ion (e.g., potassium and/or sodium) and/or fluid imbalances (e.g., overloads).

[00266] The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups (e.g., polyacrylate polymers) and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer (alternatively, counterions to about 5%) to about 10%>, about 5% to about 15%, about 5% to about 20%>, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%o, about 15%) to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25%) to about 30% of the carboxylate groups in the polymer, or any of about 5%, about 10%), about 15%), about 20%, about 25%, or about 30% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may be used in methods for the removal of fluid and/or ions (e.g., potassium and/or sodium) from a subject, i.e., The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups (e.g., polyacrylate polymers), and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer (alternatively, counterions to about 5% to about 10%, about 5% to about 15%, about 5%) to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%), about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in the polymer, or any of about 5%, about 10%, about 15%, about 20%, about 25%, or about 30% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may be used in methods for the removal of fluid from a subject.

- I l l - [00267] The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups (e.g., polyacrylate polymers) and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 15%) to about 20%>, about 15% to about 25%, about 15% to about 30%>, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25%o to about 30%, or about 25% to about 35% of the carboxylate groups in the polymer, or any of about 15%, about 20%, about 25%, about 30%, or about 35% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may be used in methods for the removal of fluid and/or ions (e.g., potassium and/or sodium) from a subject, i.e., The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups (e.g., polyacrylate polymers), and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25% to about 30%), or about 25% to about 35% of the carboxylate groups in the polymer, or any of about 15%), about 20%), about 25%, about 30%, or about 35% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may be used in methods for the removal of fluid from a subject.

[00268] The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups (e.g., polyacrylate polymers), and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer (alternatively, counterions to about 5%) to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%o, about 15%) to about 30%>, about 20%> to about 25%, about 20%> to about 30%>, or about 25%o to about 30%> of the carboxylate groups in the polymer, or any of about 5%, about 10%), about 15%), about 20%>, about 25%, or about 30%> of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may also be used in methods for treating diseases or disorders associated with increased retention of fluid and/or ion imbalances.

[00269] The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups (e.g., polyacrylate polymers), and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25%) to about 30%>, or about 25% to about 35% of the carboxylate groups in the polymer, or any of about 15%, about 20%, about 25%, about 30%, or about 35% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may also be used in methods for treating diseases or disorders associated with increased retention of fluid and/or ion imbalances.

[00270] The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups, (e.g., polyacrylate polymers) and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 5%) to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%), about 15%) to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25%) to about 30% of the carboxylate groups in the polymer, or any of about 5%, about 10%, about 15%), about 20%>, about 25%, or about 30%> of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may also be used in methods to treat end stage renal disease (ESRD), chronic kidney disease (CKD), congestive heart failure (CHF), hyperkalemia, hypernatremia, or hypertension.

[00271] The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups, (e.g., polyacrylate polymers) and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 15%) to about 20%>, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25%) to about 30%, or about 25% to about 35% of the carboxylate groups in the polymer, or any of about 15%, about 20%, about 25%, about 30%, or about 35% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may also be used in methods to treat end stage renal disease (ESRD), chronic kidney disease (CKD), congestive heart failure (CHF), hyperkalemia, hypernatremia, or hypertension.

[00272] The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups (e.g., polyacrylate polymers), and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 5%) to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%), about 15%) to about 30%, about 20% to about 25%, about 20% to about 30%, or about 25%) to about 30% of the carboxylate groups in the polymer, or any of about 5%, about 10%), about 15%), about 20%, about 25%, or about 30% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may be used to remove one or more ions selected from the group consisting of: sodium, potassium, calcium, magnesium, iron, and/or ammonium.

[00273] The disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers which comprise repeat units containing carboxylic acid groups (e.g., polyacrylate polymers), and wherein the polymer further comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer (alternatively, counterions to about 15%) to about 20%, about 15% to about 25%, about 15% to about 30%>, about 15% to about 35%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 25%o to about 30%, or about 25% to about 35% of the carboxylate groups in the polymer, or any of about 15%, about 20%, about 25%, about 30%, or about 35% of the carboxylate groups in the polymer), and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer, may be used to remove one or more ions selected from the group consisting of: sodium, potassium, calcium, magnesium, iron, and/or ammonium.

[00274] In some embodiments, the polymers, compositions comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers as disclosed herein may be substantially coated with a coating, e.g. , an enteric coating, that allows it to pass through the gut, e.g., upper gastrointestinal tract, and open in the intestine where the polymer may absorb fluid and/or specific ions that are concentrated in that particular portion of the intestine. In other embodiments, the polymers, compositions comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers disclosed herein do not comprise such a coating. In some embodiments, the absorbent material, i.e., polymer as disclosed herein, may be encapsulated in a capsule. In one embodiment, the capsule may be substantially coated with a coating, e.g., an enteric coatingi that allows it to pass through the gut and open in the intestine where the capsule may release the polymer to absorb fluid or specific ions that are concentrated in that particular position of the intestine. In another embodiment, the capsule does not contain such a coating. Individual particles of polymer or groups of particles may be encapsulated or alternatively, larger quantities of beads or particles may be encapsulated together.

[00275] In some embodiments, polymers as disclosed herein may be milled to give finer particles in order to increase drug loading of capsules, or to provide better palatability for formulations such as gels, bars, puddings, or sachets. In addition, milled particles or groups of particles, or unmilled polymeric material (e.g., beads) may be coated with various common pharmaceutical coatings. These coatings may or may not have enteric properties but will have the common characteristic that they will separate the polymer from the tissues of the mouth and prevent the polymer from adhering to tissue. For example, such coatings may include, but are not limited to: a single polymer or mixtures thereof, such as may be selected from polymers of ethyl cellulose, polyvinyl acetate, cellulose acetate, polymers such as cellulose phthalate, acrylic based polymers and copolymers or any combination of soluble, insoluble polymers or polymer systems, waxes and wax based coating systems.

[00276] In some embodiments, the polymers disclosed herein for administration to an individual or inclusion in a composition, formulation, or dosage form for administration to an individual, e.g., for use in a method of treatment as disclosed herein, are individual particles or particles agglomerated to form a larger particle (for example, flocculated particles), and have a diameter of about 1 to about 10,000 microns (alternatively, about 1 micron to about 50 microns, about 10 microns to about 50 microns, about 10 microns to about 200 microns, about 50 microns to about 100 microns, about 50 microns to about 200 microns, about 50 microns to about 1000 microns, about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or about 5000 microns to about 10,000 microns). In some embodiments, the particles or agglomerated particles have a diameter of about 1, about 5, about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, about 150, about 160, about 170, about 180, about 190, about 200, about 250, about 300, about 350, about 400, about 450, about 500, about 550, about 600, about 650, about 700, about 750, about 800, about 850, about 900, about 950, about 1000 , about 1500, about 2000, about 2500, about 3000, about 3500, about 4000, about 4500, about 5000, about 5500, about 6000, about 7000, about 7500, about 8000, about 8500, about 9000, about 9500, or about 10,000 microns. In one embodiment, the particles with a diameter of about 1 micron to about 10 microns.

[00277] In certain exemplary embodiments, the crosslinked cation-binding polymer, as described, for example, for administration to an individual or inclusion in a composition, formulation, or dosage form for administration to an individual, e.g. , for use in a method of treatment as disclosed herein, is a crosslinked polyacrylate polymer (i.e., derived from acrylic acid monomers or a salt thereof) that comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer, and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer. For example, the polymer may be a polyacrylate polymer crosslinked with about 0.08 mol% to about 0.2 mol% crosslinker or alternatively from about 0.025 mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.% to about 0.3 mol.%., and for example, may comprise an in vitro saline absorption capacity {e.g., saline holding capacity) of at least about 20 times its weight (e.g., at least about 20 grams of saline per gram of polymer, or "g/g"), at least about at least about 30 times its weight, at least about 40 times its weight, at least about 50 times its weight, at least about 60 times its weight, at least about 70 times its weight, at least about 80 times its weight, at least about 90 times its weight, at least about 100 times its weight, or more. In some embodiments, the crosslinked polyacrylate polymer comprises individual particles or particles that are agglomerated (for example, flocculated) to form a larger particle, wherein the individual or agglomerated particle diameter is about 1 to about 10,000 microns (alternatively, about 1 micron to about 10 microns, about 1 micron to about 50 microns, about 10 microns to about 50 microns, about 10 microns to about 200 microns, about 50 microns to about 100 microns, about 50 microns to about 200 microns, about 50 microns to about 1000 microns, about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or about 5000 microns to about 10,000 microns. In some embodiments, administration of such a crosslinked polyacrylate polymer, comprising comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30%> of the carboxylate groups in the polymer, does not change or does not significantly change acid/base status {e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, a crosslinked polyacrylate polymer, comprising comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer, is administered with an added base {e.g., up to about 0.9 equivalents of added base per equivalents of carboxylate groups in the polymer), and such administration of the polymer and base does not change or does not significantly change acid/base status {e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood H, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, such a crosslinked polyacrylate polymer, comprising calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in the polymer, may be administered, optionally with added base as described herein, to an individual for removal of fluid and/or ions, for example, sodium and/or potassium cations, wherein such administration does not change or does not significantly change acid/base status (e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject.

[00278] In certain exemplary embodiments, the crosslinked cation-binding polymer, as described, for example, for administration to an individual or inclusion in a composition, formulation, or dosage form for administration to an individual, e.g. , for use in a method of treatment as disclosed herein, is a crosslinked polyacrylate polymer (i.e., derived from acrylic acid monomers or a salt thereof) that comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer, and wherein sodium cations (if present) are counterions to no more than about 5% of the carboxylate groups in the polymer. For example, the polymer may be a polyacrylate polymer crosslinked with about 0.08 mol% to about 0.2 mol% crosslinker or alternatively from about 0.025 mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.% to about 0.3 mol.%., and for example, may comprise an in vitro saline absorption capacity (e.g., saline holding capacity) of at least about 20 times its weight (e.g., at least about 20 grams of saline per gram of polymer, or "g/g"), at least about at least about 30 times its weight, at least about 40 times its weight, at least about 50 times its weight, at least about 60 times its weight, at least about 70 times its weight, at least about 80 times its weight, at least about 90 times its weight, at least about 100 times its weight, or more. In some embodiments, the crosslinked polyacrylate polymer comprises individual particles or particles that are agglomerated (for example, flocculated) to form a larger particle, wherein the individual or agglomerated particle diameter is about 1 to about 10,000 microns (alternatively, about 1 micron to about 10 microns, about 1 micron to about 50 microns, about 10 microns to about 50 microns, about 10 microns to about 200 microns, about 50 microns to about 100 microns, about 50 microns to about 200 microns, about 50 microns to about 1000 microns, about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or about 5000 microns to about 10,000 microns. In some embodiments, administration of such a crosslinked polyacrylate polymer, comprising comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer, does not change or does not significantly change acid/base status (e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, a crosslinked polyacrylate polymer, comprising comprises calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15%) to about 35% of the carboxylate groups in the polymer, is administered with an added base (e.g., up to about 0.8 equivalents of added base per equivalents of carboxylate groups in the polymer), and such administration of the polymer and base does not change or does not significantly change acid/base status (e.g., acid/base balance) in an individual to whom it is administered, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, such a crosslinked polyacrylate polymer, comprising calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35% of the carboxylate groups in the polymer, may be administered, optionally with added base as described herein, to an individual for removal of fluid and/or ions, for example, sodium and/or potassium cations, wherein such administration does not change or does not significantly change acid/base status (e.g., acid/base balance) in the individual, for example, as measured by serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. [00279] In some embodiments, the polymer may be mixed with one or more base(s) in the same composition, formulation, and/or dosage form and may be in contact with fluid within the dosage from, such as suspensions or gels. To prevent interaction of the crosslinked cation-binding polymer and the base component before administration to a subject, pharmaceutical coatings known in the art can be used to coat the polymer, the base, or both to prevent or impede interaction of the polymer and the base. In some embodiments, the pharmaceutical coating may have enteric properties. As example, pharmaceutical coatings may include but are not limited to: a single polymeric coating or mixtures of more than one pharmaceutical coating, such as may be selected from polymers of ethyl cellulose, polyvinyl acetate, cellulose acetate; polymers such as cellulose phthalate, acrylic based polymers and copolymers, or any combination of soluble polymers, insoluble polymers and/or polymer systems, waxes and wax based coating systems. In alternate embodiments, the polymer and base are administered in separate dosage forms.

[00280] A subject (e.g., an individual or patient), as disclosed herein, includes a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, farm animals (such as cows), sport animals, pets (such as cats, dogs and horses), primates, and rodents (such as mice and rats). For purposes of treatment, prognosis and/or diagnosis, a subject includes any animal such as those classified as a mammal, including humans, domestic and farm animals, and zoo, wild, sports, or pet animals, such as dogs, horses, cats, cows, etc. Preferably, the subject for treatment, prognosis and/or diagnosis is human.

[00281] A disease or disorder includes any condition that would benefit from treatment with a composition as disclosed herein. This includes both chronic and acute diseases or disorders, including those pathological conditions which predispose the subject to the disease or disorder in question.

[00282] As used herein, treatment or treating refers to clinical intervention in an attempt to alter the natural course of the subject being treated, and can be performed either for prophylaxis (e.g., prevention) or during the course of clinical pathology (e.g., after the subject is identified as having a disease or disorder or the symptoms of a disease or disorder). Desirable effects of treatment include preventing occurrence or recurrence of disease, alleviation of symptoms, and/or diminishment of any direct or indirect pathological consequences of the disease or disorder, decreasing the rate of disease progression, amelioration or palliation of the disorder, and remission or improved prognosis. Terms such as treating/treatment/to treat or alleviating/to alleviate refer to both 1) therapeutic measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed disease or disorder (e.g., a pathologic condition or disorder) and 2) prophylactic or preventative measures that prevent and/or slow the development of a disease or disorder (e.g., a targeted pathologic condition or disorder). Thus, those in need of treatment may include those already with the disease or disorder; those prone to have the disease or disorder; and those in whom the disease or disorder is to be prevented.

[00283] An effective amount refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic or prophylactic result. A therapeutically effective amount of a composition disclosed herein, may vary according to factors such as the disorder, age, sex, and weight of the subject, and the ability of the composition to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the composition are outweighed by the therapeutically beneficial effects. A prophylactically effective amount refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically but not necessarily, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount may be less than the therapeutically effective amount. In some embodiments, a therapeutically effective amount includes administration of about 1 g to about 30 g or up to 100 g or more per day of a disclosed cross-linked polymer to an individual. In some embodiments, a prophylactically effective amount includes administration of about lg to about 30 g or up to 100 g or more per day of a disclosed cross-linked polymer to an individual. In various embodiments, base is co-administered at up to about 0.9 equivalents, for example, about 0.05 equivalents, about 0.1 equivalents, about 0.15 equivalents, about 0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about 0.35 equivalents, about 0.4, equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.55 equivalents, about 0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75 equivalents, about 0.8 equivalents, about 0.85 equivalents, or about 0.9 equivalents with respect to carboxylic acid groups on the polymer. A therapeutically or prophylactically effective amount of polymer and base may be administered in a single dosage or multiple doses, for example, administered once per day or administered 24 or more times daily, i.e., divided into and administered as 1, 2, 3, 4, or more doses per day, or administered at intervals of 2, 3, 4, 5, or 6 days, weekly, bi-weekly, etc.. [00284] Pharmaceutically acceptable includes approved or approvable by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, including humans. A pharmaceutically acceptable salt includes a salt of a compound that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. A pharmaceutically acceptable excipient, carrier or adjuvant includes an excipient, carrier or adjuvant that can be administered to a subject, together with at least one composition of the present disclosure, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic or prophylactic amount of the composition. A pharmaceutically acceptable vehicle includes a diluent, adjuvant, excipient, or carrier with which at least one composition of the present disclosure is administered.

[00285] Polymers, or compositions, formulations, and/or dosage forms comprising cross- linked cation binding polymers as disclosed herein can be used either alone or in combination with one or more other agents for administration to a subject (e.g., in a therapy or prophylaxis). As described herein, such combined therapies or prophylaxis include combined administration (where the polymer, composition, formulation, and/or dosage form and one or more agents are included in the same or separate composition, formulation, and/or dosage form) and separate administration, in which case, administration of the polymer, composition, formulation, and/or dosage form disclosed herein can occur prior to, contemporaneous with and/or following, administration of the one or more other agents (e.g., for adjunct therapy or intervention). Thus, co-administered or co-administration includes administration of the polymers, compositions, formulations, and/or dosage forms of the present disclosure before, during and/or after the administration of one or more additional agents or therapies.

[00286] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers are useful for treating a disease or disorder. Typically, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymer, and/or dosage forms comprising the disclosed polymers are co-administered with a base, as described herein. In some embodiments, the disease or disorder is one or more of: heart failure, a renal insufficiency disease, end stage renal disease, liver cirrhosis, chronic renal insufficiency, chronic kidney disease, fluid overload, fluid maldistribution, edema, pulmonary edema, peripheral edema, lymphedema, nephrotic edema, idiopathic edema, ascites, cirrhotic ascites, interdialytic weight gain, high blood pressure, hyperkalemia, hypernatremia, abnormally high total body sodium, hypercalcemia, tumor lysis syndrome, head trauma, an adrenal disease, hyporeninemic hypoaldosteronism, hypertension, salt-sensitive hypertension, refractory hypertension, renal tubular disease, rhabdomyolysis, crush injuries, renal failure, acute tubular necrosis, insulin insufficiency, hyperkalemic periodic paralysis, hemolysis, malignant hyperthermia, pulmonary edema secondary to cardiogenic pathophysiology, pulmonary edema with non-cardiogenic origin, drowning, acute glomerulonephritis, allergic pulmonary edema, high altitude sickness, Adult Respiratory Distress Syndrome, traumatic edema, cardiogenic edema, acute hemorrhagic edema, heatstroke edema, facial edema, eyelid edema, angioedema, cerebral edema, scleral edema, nephritis, nephrosis, nephrotic syndrome, glomerulonephritis, and/or renal vein thrombosis.

[00287] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations, comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, as disclosed herein, are useful for treating a disease or disorder involving an ion imbalance in a subject by administering to the subject an effective amount of the polymer, composition, formulation, and/or a dosage form (e.g., an effective amount), as disclosed herein. In some embodiments, the polymers, compositions, formulations, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the disease or disorder is or includes hyperkalemia. In some embodiments, the disease or disorder is or includes hypernatremia. In some embodiments, the disease or disorder is or includes an abnormally high total body sodium level. In some embodiments, the disease or disorder is or includes an abnormally high potassium level. In some embodiments, the disease or disorder is or includes hypernatremia and hyperkalemia. In some embodiments, the disease or disorder is or includes fluid overload. In some embodiments, the disease or disorder is or includes fluid overload and hyperkalemia. In some embodiments, the disease or disorder is or includes fluid overload and hyperkalemia and abnormally high total body sodium level.

[00288] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers as disclosed herein are useful for treating a subject with heart failure by administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form as disclosed herein. In some embodiments, the polymers, compositions, formulations, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the subject has both heart failure and chronic kidney disease. In some related embodiments, the methods further comprise reducing one or more symptoms of a fluid overload state in the subject. Symptoms of a fluid overload state in a subject are known to those skilled in the art, and may include, for example and without limitation, difficulty breathing when lying down, ascites, fatigue, shortness of breath, difficulty breathing on exertion, increased body weight, peripheral edema, and/or pulmonary edema. In some related embodiments, the subject may be on concomitant dialysis therapy. In some further related embodiments, the dialysis therapy may be reduced or discontinued after administration of a disclosed polymer, a composition comprising the disclosed polymer, a formulation comprising the disclosed polymer, and/or a dosage form comprising the disclosed polymer, as disclosed herein. In some related embodiments, the method further comprises identifying the subject as having heart failure before administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising the disclosed polymer. In some embodiments, administration of the disclosed polymers, compositions comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, as described herein, improves or ameliorates at least one symptom of heart failure, for example, at least one symptom that impacts the subject's quality of life and/or physical function. For example, administration may result in body weight reduction, dyspnea improvement (for example, overall and dyspnea at exertion), six minute walk test improvement, and/or improvement or absence of peripheral edema. In some embodiments, administration of the disclosed polymers, compositions comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, as described herein, results in reduction of patient classification by at least one heart failure class, according to the New York Heart Association Class I, II, III, IV functional classification syste

[00289] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, as disclosed herein, are useful for treating a subject with end stage renal disease (ESRD) by administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form, as disclosed herein. In some embodiments, the polymers, compositions, formulations, and/or dosage forms may be co- administered with a base, as described herein. In some related embodiments, the subject is on concomitant dialysis therapy. In some embodiments, the method reduces blood pressure in an ESRD subject on concomitant dialysis therapy, for example, pre-dialysis, post- dialysis, and/or interdialytic systolic and diastolic blood pressure may be reduced. In some embodiments, the method reduces interdialytic weight gain in an ESRD subject on concomitant dialysis therapy. In some embodiments, the subject also has heart failure. In some embodiments, one or more symptoms of intradialytic hypotension are improved after administration of a disclosed polymer, a composition comprising a disclosed polymer, a formulation, comprising a disclosed polymer, and/or a dosage form comprising a disclosed polymer, as disclosed herein. For example and without limitation, incidences of vomiting, fainting and/or drops in blood pressure levels are reduced or eliminated. In some embodiments, the subject experiences one or more of: a reduced frequency of emergency dialysis sessions, a reduced frequency of inadequate dialysis sessions, a reduced frequency of dialysis sessions on low-potassium dialysis bath, and/or reduced frequency or reduced severity of EKG signs during dialysis sessions. In some embodiments, one or more symptom of intradialytic hypotension are reduced or eliminated after administration of a polymer, a composition comprising a disclosed polymer, a composition comprising a disclosed polymer, a formulation comprising a disclosed polymer, and/or a dosage form comprising a disclosed polymer. Symptoms of intradialytic hypotension are known to those skilled in the art and may include, for example, vomiting, fainting, an abrupt decrease in blood pressure, seizures, dizziness, severe abdominal cramping, severe leg or arm muscular cramping, intermittent blindness, infusion, medication, and dialysis session interruption or discontinuation. In some embodiments, ESRD subjects may experience an improvement in physical function as expressed by increase in performance in the 6 Minute Walk Test.

[00290] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, as disclosed herein, are useful for treating a subject having chronic kidney disease. In some embodiments, the methods comprise administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form. In some embodiments, the polymers, compositions, formulations, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the methods further comprise identifying the subject as having a chronic kidney disease before administration of a disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein. In some related embodiments, the methods further comprise reducing one or more symptoms of a fluid overload state in the subject. In some embodiments, a comorbidity of chronic kidney disease is reduced, alleviated, and/or eliminated after administration of a polymer, a composition comprising a disclosed polymer, a formulation comprising a disclosed polymer, and/or a dosage form comprising a disclosed polymer. Comorbidities of chronic kidney disease are known to those skilled in the art and include, for example, fluid overload, edema, pulmonary edema, hypertension, hyperkalemia, excess total body sodium, heart failure, ascites, and/or uremia. In some embodiments, CKD patients may experience prevention of doubling of serum creatinine over the duration of a study (for example, 1 to 2 years), prevention of disease progression to dialysis, and/or prevention of death and CKD related hospitalizations and/or complications.

[00291] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the polymers as, disclosed herein, are useful for treating a subject having hypertension. In some embodiments, the methods comprise administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form. In some embodiments, the polymers, compositions, formulations, and/or dosage forms may be coadministered with a base, as described herein. In some embodiments, the methods further comprise identifying that the subject has hypertension before administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein. As used herein, the term hypertension includes the various subtypes of hypertension known to those skilled in the art, for example and without limitation: primary hypertension, secondary hypertension, salt sensitive hypertension, refractory hypertension, and combinations thereof. In some embodiments, the method is effective in reducing the subject's blood pressure. In related embodiments, the method may further comprise determining a blood pressure level before, after, or both before and after administration of the polymer, composition comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer as disclosed herein. For example, the method may further comprise determining the subject's diastolic blood pressure, systolic blood pressure, and/or mean arterial pressure ("MAP") before, after, or both before and after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, one or more symptom of a fluid overload state is reduced, improved, or alleviated by administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein. In some related embodiments, the method may further comprise determining a fluid overload state symptom before, after, or both before and after administration of a disclosed polymer, composition comprising a disclosed polymer formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer as disclosed herein. For example, the method may further comprise observing an improvement in the subject's breathing while lying down, ascites, fatigue, shortness of breath, body weight, peripheral edema, and/or pulmonary edema. In some embodiments, the subject is on concomitant diuretic therapy. As used herein, the term diuretic therapy refers to administration of pharmaceutical compositions (e.g., diuretic agents), and non- chemical intervention, such as dialysis or restriction of fluid intake. Diuretic agents are known to those skilled in the art and include, for example, furosemide, bumetanide, torsemide, hydrochlorthiazide, amiloride and/or spironolactone. In some related embodiments, the diuretic therapy may be reduced or discontinued following administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein.

[00292] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers,, and/or dosage forms comprising the disclosed polymers, as disclosed herein, are useful for treating hyperkalemia in a subject. In some embodiments, the method comprises administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form as disclosed herein. In some embodiments, the polymers, compositions, formulations, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the method further comprises identifying the subject as having hyperkalemia, or as having a risk of developing hyperkalemia, before administering the disclosed polymer, composition comprising a disclosed polymer, formulation, and/or dosage form comprising a disclosed polymer, as disclosed herein. In some embodiments, the method may further comprise determining a potassium ion level in the subject before administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein. In some related embodiments, the potassium ion level may be within a normal range, slightly elevated, or elevated before administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, the subject has been prescribed or will be administered a drug known to increase potassium levels. In some embodiments, the subject has already ingested a drug known to increase potassium levels. In some embodiments, the method may further comprise determining a second, reduced potassium ion level in the subject after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, an acid/base status (e.g., acid/base balance) associated with the subject does not change, for example, as measured by, serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap, after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject.

[00293] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers,, and/or dosage forms comprising the disclosed polymers, as disclosed herein, are useful for treating a high sodium level, e.g., an abnormally high sodium level such as hypernatremia, in a subject. In some embodiments, the method comprises administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form as disclosed herein. In some embodiments,, the disclosed polymers, compositions, formulations, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the method further comprises identifying the subject as having a high sodium level, or as having a risk of developing a high sodium level, before administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, the method may further comprise determining a sodium ion level, e.g., a total body sodium ion level, in the subject before administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer,, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some related embodiments, the sodium ion level, e.g. , serum sodium ion level, may be within a normal range, slightly elevated, or elevated before administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, the method may further comprise determining a second, reduced sodium ion level, e.g., a total body sodium ion level, in the subject after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, an acid/base status {e.g., acid/base balance) associated with the subject does not change, for example, as measured by, serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap, after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, the subject has taken or will take a drug known to increase sodium levels, for example and without limitation: estrogen containing compositions, mineralocorticoids, osmotic diuretics {e.g., glucose or urea), vaptans {e.g., tolvaptan, lixivaptan), lactulose, cathartics {e.g., phenolphthalein), phenytoin, lithium, Amphotericin B, demeclocycline, dopamine, ofloxacin, orlistat, ifosfamide, cyclophosphamide, hyperosmolar radiographic contrast agents {e.g., gastrographin, renographin), cidofovir, ethanol, foscarnet, indinavir, libenzapril, mesalazine, methoxyflurane, pimozide, rifampin, streptozotocin, tenofir, triamterene, and/or cholchicine. In some embodiments, administration of the disclosed polymer, compositions comprising the disclosed polymer, formulations comprising the disclosed polymer, and/or dosage forms comprising the disclosed polymer may further comprise increasing a dose of one or more additional agents, for example, an agent known to cause an increase in sodium levels. In some embodiments, the method further comprises increasing a dose of one or more of: an aldosterone antagonist, an angiotensin II receptor blocker, and/or an angiotensin-converting enzyme inhibitor before, concomitantly, and/or after administering a disclosed polymer, a composition comprising a disclosed polymer, a formulation comprising a disclosed polymer, and/or a dosage form comprising a disclosed polymer. In some embodiments, administration of the disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer may further comprise decreasing a dose or discontinuing administration or co-administration of a diuretic.

[00294] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers ,as disclosed herein, are useful for treating a subject with a disease or disorder involving fluid overload (e.g., a fluid overload state such as heart failure, end stage renal disease, ascites, renal failure, nephritis, and nephrosis). In some embodiments, the method comprises administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form as disclosed herein. In some embodiments, the polymers, compositions, formulations, and/or dosage forms may be coadministered with a base, as described herein. In some embodiments, the subject may be on concomitant diuretic therapy. In some embodiments, the method may further comprise identifying a fluid overload state in the subject, or identifying a risk that the subject will develop a fluid overload state before administration of a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer. Methods of identifying a fluid overload state or a risk of developing a fluid overload state are known to those skill in the art and may include, for example and without limitation: assessing difficulty breathing when lying down, ascites, fatigue, shortness of breath, increased body weight, peripheral edema, and/or pulmonary edema associated with the subject. In some embodiments, an acid/base status (e.g. , acid/base balance) associated with the subject, for example, as measured by, serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap, does not change within about one day of administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer,, and/or dosage form comprising the disclosed polymer, as disclosed herein. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject.

[00295] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the polymers, as disclosed herein, are useful for treating a subject with a disease or disorder involving fluid maldistribution (e.g., a fluid maldistribution state such as pulmonary edema, angioneurotic edema, ascites, high altitude sickness, adult respiratory distress syndrome, uticarial edema, papille edema, facial edema, eyelid edema, cerebral edema, and scleral edema). In some embodiments, the method comprises administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form, as disclosed herein. In some embodiments, the polymers, compositions, formulations,, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the method may further comprise identifying a fluid maldistribution state or a risk of developing a fluid maldistribution state in the subject before administering to the subject a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer.

[00296] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, as disclosed herein, are useful for treating edema in a subject. In some embodiments, the method comprises administering to the subject an effective amount of the polymer, composition, formulation, and/or dosage form, as disclosed herein. In some embodiments, the polymers, compositions, formulations, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the method may further comprise identifying an edematous state or a risk of developing an edematous state in the subject before administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed , as disclosed herein. In some embodiments, the edematous state is nephritic edema, pulmonary edema, peripheral edema, lymphedema, and/or angioneurotic edema. In some embodiments, the subject is on concomitant diuretic therapy. In some related embodiments, the diuretic therapy may be reduced or discontinued after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, the method may further comprise, before administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein, determining one or more of: a baseline level of one or more ions (e.g., sodium, potassium, lithium and/or magnesium) in the subject, a baseline total body weight associated with the subject, a baseline total body water level associated with the subject, a baseline total extracellular water level associated with the subject (e.g. , a measure of the degree of edema in a particular site as evidenced by depth of pitting or extent of x-ray changes, and/or a baseline total intracellular water level associated with the subject. In some embodiments, the method may further comprise, after administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein, determining one or more of: a second level of one or more ions in the subject, a second total body weight associated with the subject, a second total body water level associated with the subject, a second total extracellular water level associated with the subject, and/or a second total intracellular water level associated with said subject. In some embodiments, the second level is lower than the corresponding baseline level. In some embodiments, an acid/base status (e.g, acid/base balance) associated with said subject, for example, as measured by, serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap, does not significantly change within about one day of administration of the disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, a blood pressure level associated with the subject after administration of the disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer,, and/or dosage form comprising a disclosed polymer is substantially lower than a baseline blood pressure level associated with the subject determined before administration of the disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer,, and/or dosage form comprising a disclosed polymer. In some embodiments, one or more symptoms of edema are reduced and/or eliminated following administration of a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein. Symptoms of edema are known to those skilled in the art; some non- limiting examples include: difficulty breathing when lying down, shortness of breath, peripheral edema, and leg edema.

[00297] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers according to the present disclosure are useful for treating ascites in a subject. In some embodiments, the method comprises administering to the subject an effective amount of the polymer, composition, formulation, and/or a dosage form, as disclosed herein. In some embodiments, the disclosed polymers, compositions, formulations, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the method may further comprise identifying an ascitic state or a risk of developing an ascitic state in the subject. In some embodiments, the subject is on concomitant diuretic therapy. In some related embodiments, the diuretic therapy may be reduced or discontinued after administration of the disclosed composition. In some embodiments, the subject may have taken, or will take, a drug known to increase potassium levels.

[00298] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, as disclosed herein, are useful for treating nephrotic syndrome in a subject. In some embodiments, the method comprises administering to said subject an effective amount of the polymer, composition, formulation, and/or dosage form, as disclosed herein. In some embodiments, the disclosed polymers, compositions, formulations, and/or dosage forms may be co-administered with a base, as described herein. In some embodiments, the method further comprises identifying the subject as having nephrotic syndrome, or as having a risk of developing nephrotic syndrome, before administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer. In some embodiments, the method may further comprise determining one or more of: a level of one or more ions (e.g., sodium, potassium calcium, lithium, and/or magnesium) in the subject, a total body weight associated with the subject, a total body water level associated with the subject, a total extracellular water level associated with the subject, and/or a total intracellular water level associated with the subject before administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer. In some embodiments, the method may further comprise determining a second, lower level of one or more of: a level of one or more ions in the subject, a total body weight associated with the subject, a total body water level associated with the subject, a total extracellular water level associated with the subject, and/or a total intracellular water level associated with the subject after administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer. In some embodiments, an acid/base status (e.g, acid/base balance) associated with the subject, for example, as measured by, serum total bicarbonate, serum total C0₂, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap, does not significantly change within about one day of administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising a disclosed polymer. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. In some embodiments, a blood pressure level associated with the subject after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer is substantially lower than a baseline blood pressure level associated with the subject before the administration(s). In some embodiments, one or more symptoms of fluid overload is alleviated, reduced, or eliminated after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer. In some related embodiments, the symptom may be one or more of: difficulty breathing when lying down, shortness of breath, peripheral edema, and/or leg edema. In some embodiments, the subject may be on concomitant diuretic therapy. In some related embodiments, the diuretic therapy may be reduced or eliminated after administration of the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer.

[00299] In some embodiments, methods according to the present disclosure may further comprise administering to the subject an additional agent such as mannitol, sorbitol, calcium acetate, sevelamer carbonate (Renvela®), lanthanum carbonate, and/or sevelamer hydrochloride.

[00300] In some embodiments, methods according to the present disclosure may further comprise administering to the subject an agent known to increase potassium levels. As used herein, the term "an agent known to increase potassium levels" refers to agents that are known to cause an increase, are suspected of causing an increase, or are correlated with an increase in potassium levels, e.g., serum potassium levels, upon administration. For example and without limitation, agents known to cause an increase in potassium levels may include: a tertiary amine, spironolactone, fluoxetine, pyridinium and its derivatives, metoprolol, quinine, loperamide, chlorpheniramine, chlorpromazine, ephedrine, amitryptyline, imipramine, loxapine, cinnarizine, amiodarone, nortriptyline, a mineralocorticosteroid, propofol, digitalis, fluoride, succinylcholine, eplerenone, an alpha- adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist, benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, candesartan, eprosartan, irbesartan, losartan, valsartan, telmisartan, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, nadolol, propranolol, sotalol, timolol, canrenone, aliskiren, aldosterone synthesis inhibitors, and/or VAP antagonists. In some embodiments, administration of the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers may further comprise increasing a dose of one or more additional agents, for example, an agent known to cause an increase in potassium levels. In some embodiments, administration of the polymers, compositions comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers may further comprise decreasing a dose or discontinuing administration or co-administration of a diuretic, for example, as a result of having treated fluid overload with a disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, as disclosed herein.

[00301] In some embodiments, methods according to the present disclosure may further comprise administering to the subject an agent known to increase sodium levels. As used herein, the term "an agent known to increase sodium levels" refers to agents that are known to cause an increase, are suspected of causing an increase, or are correlated with an increase in sodium levels upon administration. For example and without limitation, agents known to cause an increase in sodium levels may include: estrogen containing compositions, mineralocorticoids, osmotic diuretics (e.g., glucose or urea), vaptans (e.g., tolvaptan, lixivaptan), lactulose, cathartics (e.g., phenolphthalein), phenytoin, lithium, Amphotericin B, demeclocycline, dopamine, ofloxacin, orlistat, ifosfamide, cyclophosphamide, hyperosmolar radiographic contrast agents (e.g., gastrographin, renographin), cidofovir, ethanol, foscarnet, indinavir, libenzapril, mesalazine, methoxyflurane, pimozide, rifampin, streptozotocin, tenofir, triamterene, and/or cholchicine. In some embodiments, administration of the polymers, compositions comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers may further comprise increasing a dose of one or more additional agents, for example, an agent known to cause an increase in sodium levels. In some embodiments, administration of the polymers, compositions comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers may further comprise decreasing a dose or discontinuing administration or co-administration of a diuretic.

[00302] In some embodiments, methods according to the present disclosure may further comprise determining a baseline level of one or more ions in a subject before administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or the dosage form comprising a disclosed polymer, as disclosed herein, and determining a second level of the one or more ions in the subject after administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In related embodiments, a baseline level of potassium is determined in a subject. In another embodiment, a baseline level of sodium is determined in a subject. Thereafter, a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein, is administered to the subject, followed by a determination of a second potassium and/or sodium level. In some embodiments, the second potassium and/or sodium level is lower than the baseline potassium level.

[00303] In some embodiments, methods according to the present disclosure may further comprise determining a baseline total body weight associated with a subject before administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein, and determining a second total body weight associated with the subject after administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, the second total body weight is lower than the baseline total body weight. Any suitable method for determining the total body weight associated with a subject may be used.

[00304] In some embodiments, methods according to the present disclosure may further comprise determining a baseline total water level, e.g., total body water level, associated with a subject before administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer ,as disclosed herein, and determining a second total water level, e.g., total body water level, associated with the subject after administering the disclosed polymer, composition comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, the second total water level, e.g., total body water level, is lower than the baseline total water level, e.g., total body water level. Any suitable method for determining a total water level associated with a subject may be used, for example, by bioimpedance measurement, or through invasive procedures, such as central vein catheters for measurement of pulmonary wedge pressure.

[00305] In some embodiments, methods according to the present disclosure may further comprise determining a baseline total extracellular water level associated with a subject before administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein, and determining a second total extracellular water level associated with the subject after administering the polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, the second total extracellular water level is lower than the baseline total extracellular water level. Any suitable method for determining a total extracellular water level associated with a subject may be used, for example, by bioimpedance measurement, or through invasive procedures, such as central vein catheters for measurement of pulmonary wedge pressure.

[00306] In some embodiments, methods according to the present disclosure may further comprise determining a baseline total intracellular water level associated with a subject before administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, as disclosed herein, and determining a second total intracellular water level associated with the subject after administering the disclosed polymer, composition comprising the disclosed polymer, formulation comprising the disclosed polymer, and/or dosage form comprising the disclosed polymer, as disclosed herein. In some embodiments, the second total intracellular water level is lower than the baseline total intracellular water level. Any suitable method for determining a total intracellular water level associated with a subject may be used, for example, by bioimpedance measurement, or through invasive procedures, such as central vein catheters for measurement of pulmonary wedge pressure.

[00307] In some embodiments, methods according to the present disclosure may further comprise determining an acid/base status (e.g., acid/base balance) associated with a subject.

Any method known in the art for determining an acid/base status (e.g., acid/base balance) may be employed. In some embodiments, methods according to the present disclosure comprise determining an acid/base status (e.g., acid/base balance) associated with a subject after administering a composition according to the present disclosure.

[00308] For example, an acid/base status (e.g., acid/base balance) may be measured by serum total bicarbonate, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. In an exemplary method, anion gap may be calculated by subtracting the serum concentrations of chloride and bicarbonate (anions) from the concentrations of sodium and potassium (cations) as follows:

Anion gap = ([Na⁺] + [K⁺]) - ([CP] + [HC0₃ ])

[00309] Alternatively, in another exemplary method, anion gap may be calculated by ignoring potassium concentration as follows:

Anion gap = [Na⁺] - ([CI ] + [HC0₃ ])

[00310] In related embodiments, the acid/base status (e.g., acid/base balance) is within a normal range as set by a clinical laboratory.

[00311] In related embodiments, the acid/base status (e.g., acid/base balance) is within a normal range for the subject, and/or within a clinically acceptable range for the subject.

[00312] In some embodiments, an acid/base status (e.g., acid/base balance) associated with a subject after administering a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, according to the present disclosure, is closer to a normal level for the subject, closer to a clinically acceptable level, etc., than compared to a baseline acid/base status (e.g., acid/base balance) associated with the subject before administration of the polymer, composition, formulation, and/or dosage form.

[00313] In some embodiments, an acid/base status (e.g., acid/base balance) associated with the subject does not change or does not significantly change, for example, at the end of a time interval, or about 1 day, within about 18 hours, within about 12 hours, 10 hours, within about 9 hours, within about 8 hours, within about 7 hours, within about 6 hours, within about 5 hours, within about 4 hours, within about 3 hours, within about 2 hours, or within about 1 hour of administration of the composition. An acid/base status that does not change includes one that does not change outside the normal range or outside the normal range for the subject. [00314] Methods for determining an ion level in a subject are known to those skilled in the art. Any suitable method for determining an ion level may be used. However, determination of serum sodium levels should be avoided as such levels tend not to fluctuate, even in hypernatremic subjects. If sodium ion levels are desired, another suitable method for determining such levels should preferably be used, such as determining a subject's total body sodium level.

[00315] In some embodiments, methods according to the present disclosure may further comprise determining a blood pressure level before, after, or both before and after administration of a disclosed polymer, composition comprising a disclosed polymer, formulation comprising a disclosed polymer, and/or dosage form comprising a disclosed polymer, according to the present disclosure. A subject's blood pressure level may be determined using any suitable method known in the art. For example and without limitation, a subject's blood pressure level may be determined by measuring the subject's systolic blood pressure, the subject's diastolic blood pressure, and/or the subject's mean arterial pressure ("MAP"). In some embodiments, the subject's blood pressure is lower after treatment than before treatment.

[00316] In some embodiments, the disclosed polymers, compositions comprising the disclosed polymers, formulations comprising the disclosed polymers, and/or dosage forms comprising the disclosed polymers, according to the present disclosure, are administered as needed to reduce an ion level in a subject, and/or to maintain an acceptable level of one or more ions in a subject, and/or to reduce a fluid overload state or fluid maldistribution state in a subject. In some embodiments, compositions according to the present disclosure are administered at a frequency from 1 time per every 3 days to about 4 times per day. Preferably, the compositions according to the present disclosure are administered from about 1 time per day to about 4 times per day; for example, once or twice per day.

EXAMPLES

[00317] The following examples are for illustrative purposes only and are not to be construed as limiting in any manner. Example 1

[00318] This example demonstrates the preparation of an exemplary cross-linked polyelectrolyte polymer, such as crosslinked polyacrylic acid partially neutralized with sodium.

[00319] An inverse suspension process may be used with the following components: a monomer (e.g., acrylic acid), solvent for the monomer (e.g., hydrophilic, for example, water), base for neutralization of monomer (e.g., NaOH), lipophilic (e.g., hydrophobic) solvent (e.g., Isopar™ L), suspending agent (e.g., fumed silica such as Aerosil R972), chelating agent (e.g., Versenex™-80), polymerization initiator (e.g., sodium persulfate), and cross-linking agent (e.g., TMPTA).

[00320] A monomer solution is prepared in a vessel as the aqueous phase by dissolving an unsaturated carboxylic acid monomer (e.g., acrylic acid) in water and neutralizing with an aqueous alkali (e.g., NaOH) to a desired percentage neutralization (e.g., 70% to 95% neutralized). Just before addition of this aqueous, partially neutralized, monomer solution to the reactor, one or more polymerization initiators (e.g., sodium persulfate alone or a redox-couple, such as t-butylhydroperoxide paired with thiosulfate) are added under conditions that do not favor polymerization. Optionally, a chelating agent (e.g., Versenex™-80) can be added to the aqueous mixture ensure control of transition metal ions. An organic phase (e.g., Isopar™ L or toluene or n-heptane or cyclohexane) is placed into the main reactor (not the vessel with the aqueous monomer solution). A hydrophobic suspending agent (e.g., Aerosil R972) is dissolved or dispersed in the organic phase. A crosslinking agent is added. If the crosslinking agent is soluble in the organic phase (e.g., divinylbenzene or 1,1 ,1-trimethylolpropane triacrylate— also called TMPTA), it is added to the reactor with the organic phase. If the crosslinking agent is water soluble (e.g., highly- ethoxylated trimethylolpropane triacrylate— also called HE-TMPTA— or diacryl glycerol), the crosslinking agent is added to the aqueous phase. The aqueous phase is then added to the organic phase in the reactor, e.g., with mixing, and the reaction mixture is agitated to produce aqueous droplets of the appropriate size in the organic solvent. Simultaneously, oxygen is removed from the reaction mixture by bubbling an inert gas (e.g., nitrogen) through the reaction mixture. After adequate deoxygenation, the reaction will either begin (e.g., in the case of redox couples) or be started by increasing the temperature (e.g., in the case of sodium persulfate). A second addition of hydrophobic suspending agent may be added as the polymerization proceeds, i.e., to further stabilize the particles. Reaction is completed by maintaining an elevated temperature (e.g., 65°C) for a time adequate to allow removal, i.e., reaction of substantially all of the monomer (e.g., 2 to 4 hours). Water may then be removed by azeotropic distillation and the crosslinked cation-binding polymeric material may be isolated by filtration or centrifugation to remove the remaining organic solvent. The polymeric material may be rinsed with fresh organic solvent and dried to the desired moisture and/or organic solvent content as measured by loss on further drying. In some embodiments, less than 500 ppm of the monomer remains after polymerization. The polymer may be rinsed to remove this residual monomer.

[00321] In an exemplary method, acrylic acid (140 g) was added dropwise to a solution of 124.35 g of 50% NaOH and 140 g of deionized water while keeping the temperature below 40°C to prevent initiation of polymerization. 3.5 g of Versenex™ 80 and 0.70 g of a 10% solution of sodium persulfate were added. Meanwhile, 1200 g of Isopar™ L were charged into the main reactor. 0.80 g Aerosil R972 dissolved in 40 g of Isopar™ L and 0.50 g of TMPTA were added to the main reactor. The aqueous monomer solution was added to the reactor, which was then closed. Agitation was started at 330 RPM and argon was bubbled through the reaction mixture. After 70 minutes of bubbling argon, the reaction was heated rapidly at 4°C increase per minute. When the temperature reached 50°C, another 0.80 g of Aerosil R972 in 40 g of Isopar™ L (that had been separately bubbled with argon) was added to the reaction mixture. The reaction exotherm heated the mixture to 80°C over the next 15 minutes while the constant temperature bath was removing heat to keep the reaction mixture at 65°C. The reaction mixture cooled to 70°C at approximately 60 minutes from the start of heating. The reaction mixture was kept at 65°C to 70°C for 4 hours. The reaction mixture was allowed to cool. The resulting crosslinked cation-binding polymer was isolated by filtration and dried in vacuum at 105°C.

Example 2

[00322] This example illustrates the preparation of an exemplary crosslinked polyelectrolyte polymer by an aqueous phase reaction of a partially neutralized carboxylic acid monomer.

[00323] A monomer solution is prepared in a reactor by dissolving an unsaturated carboxylic acid monomer (e.g., acrylic acid) in water and neutralizing with an aqueous alkali (e.g., NaOH) to a desired percentage neutralization (e.g., 70 to 95 percent neutralized). Optionally, a chelating agent (e.g., Versenex™ 80) may be added to control metal ions. A suitable crosslinking agent (e.g., 1 , 1 ,1-trimethylolpropane triacrylate or diacryl glycerol) is added to the reactor. A polymerization initiator is added to the reactor. The reactor is then closed and the reaction mixture is bubbled with an inert gas (e.g., nitrogen) and agitated until adequate removal of oxygen is achieved. The reaction is then initiated either by reaching an oxygen concentration where a redox couple produces radicals or by adding heat to cause a temperature dependent initiator (e.g., persulfate salts) to produce radicals. The reaction is allowed to proceed through the exothermic heating that occurs during reaction. After 2 to 6 hours, the reaction is completed and the gel-like mass of reaction product can be removed from the reactor and cut into appropriately sized pieces. After drying, the particles can be separated by size or milled to produce the desired size or size distribution.

[00324] Thus, in an exemplary method, 140 g of acrylic acid were added dropwise to a solution of 124.35 g of 50% NaOH and 140 g of deionized water while keeping the temperature below 40°C to prevent initiation of polymerization. Then, 3.5 g of Versenex™ 80 and 0.70 g of a 10% solution of sodium persulfate were added. The final addition was 0.50 g of TMPTA. The reactor was closed and the reaction mixture agitated at 200 RPM while argon was bubbled through the mixture. After 70 minutes of bubbling argon, the reaction was initiated by heating at a rate of a 4°C temperature rise per minute. After 7 minutes, the reaction reached 55°C and the entire reaction mixture became a gel. The agitation was stopped, allowing the gel to slowly settle to the bottom of the reactor. The temperature of the heating bath was maintained at 65°C for another 4 hours. The gel was then cooled, cut into pieces, and dried in a vacuum at 105°C.

[00325] In an alternative exemplary large scale continuous production method, a monomer feed mix of approximately 6.0 g TMPTA, 2.2 kg water, 0.4 kg sodium hydroxide, and 3.0 g sodium persulfate per kg of acrylic acid was deoxygenated and polymerization initiated with 0.6 g sodium ascorbate per kg of acrylic acid. The solution was then charged to a curing conveyor belt, where the sodium acrylate solution polymerized to a gel as it traveled on the conveyor belt. The polymer gel was then mechanically cut and granulated to reduce the polymer gel particle size and then the polymer was dried. The dried polymer was then milled and sieved to a desired particle size. Example 3

[00326] This example illustrates the conversion of a partially sodium-substituted crosslinked polycarboxylic polymer prepared, for example, according to Example 1 or 2, to a crosslinked polycarboxylic acid polymer with a reduced degree of sodium substitution (e.g., an acidified polymer).

[00327] The polymer is weighed and the relative content of different cations (either from knowledge of the preparation or, more preferably, from elemental analysis of a sample) is used to determine the number of moles of carboxylate present. The polymer is then washed with an excess (e.g., twice the number of moles of carboxylates, or more) of 1 N acid (preferably HCl), either in batches or by column elution. The resulting acidified polymer is rinsed with water to remove any excess of the 1 N acid, and dried in a vacuum at 60°C.

[00328] For example, 89.65 g of a polymer produced by the technique of Example 1 were placed into a beaker and stirred with 667 mL of 1 N HCl for 2 hours. The liquid was drained and the polymeric particles were returned to the vessel. A second aliquot of 667 mL of 1 N HCl was added and the mixture was stirred for 1 hour. The liquid was drained and a third rinse with 667 mL of 1 N HCl was performed for 1 hour. The liquid was drained and the polymeric material was placed into 667 mL of deionized water and stirred for 1 hour. The liquid was drained and another 667 mL of deionized water was added. The polymeric material was then stirred for 1 hour before draining the liquid. This water washing was continued until the pH of the rinse water was above 3. The crosslinked cation- binding polymer was then dried in a vacuum at 60°C.

[00329] Alternatively, one-hundred grams of a cross-linked polyelectrolyte polymer, such as a partially neutralized cross-linked polyacrylate polymer (e.g., prepared as described in Example 1 above) was placed into a vessel. Next, about 2,250 milliliters of pure (e.g., trace metal or otherwise certified low metal) 1 M HCl was added to the vessel and then the polymer and the acid were stirred gently for two hours. The liquid was removed by decanting or filtration. If desired due to vessel size or for improved mass balance, the 2,250 milliliters of 1M HCl is divided into multiple batches and used sequentially. For instance, 750 milliliters were added, stirred with the polymer, and removed followed by two or more separate additions of 750 milliliters. The polymer was then rinsed with 2,250 milliliters of low metal content water to remove excess acid surrounding the polyelectrolyte such as a polyacrylate. The crosslinked cation-binding polymer was then dried. [00330] Further alternatively, one-hundred grams of a cross-linked polyelectrolyte polymer, such as a cross-linked polyacrylate polymer were placed into a filtration funnel or a column equipped with a bottom filter. The polymer was then rinsed with about 2,250 milliliters of pure (e.g., trace metal or otherwise certified low metal) 1 M HC1 for about an hour or more. Next, the polymer was rinsed with 2,250 milliliters of low metal content water. The crosslinked cation-binding polymer was then dried.

[00331] Exemplary acidified polymers useful as crosslinked cation-binding polymers prepared according to this Example generally have a saline holding capacity of greater than about 40 g/g (see, e.g., Examples 8 and 9); and contain less than about 5,000 ppm of sodium, less than about 20 ppm of heavy metals, less than about 500 ppm of residual monomer, less than about 2,000 ppm of residual chloride, and less than about 20 wt.% of soluble polymer. Preferably, acidified polymers useful as crosslinked cation-binding polymers prepared according to this Example have a saline holding capacity of greater than about 80 g/g (see, e.g., Examples 5 and 6); and contain less than about 500 ppm of sodium, less than about 20 ppm of heavy metals, less than about 50 ppm of residual monomer, less than about 1,500 ppm of residual chloride, and less than about 10 wt.% of soluble polymer. Crosslinked cation-binding polymers prepared according to the method of Example 1 (using acrylic acid monomers) and acidified to prepare the exemplary acidified polymers of the present Example may be referred to as "H-CLP" or "HCLP".

Example 4

[00332] This example demonstrates the preparation of substantially metal free (e.g., acid form) cross-linked polyelectrolyte polymers, such as cross-linked polyacrylic acid polymer.

[00333] In an exemplary method, substantially metal free (e.g., acid form) cross-linked polyacrylic acid polymer was prepared by placing 140 g of glacial acrylic acid (e.g., not neutralized as in Example 1) into a three to five liter reactor with 2,200 to 2,500 milliliters of dilute acid, such as 1 M HC1. A water soluble cross linking agent, such as 1,3- diglycerate diacrylate, in a ratio chosen to produce the desired saline holding capacity (e.g., 20-fold, 30-fold, 40-fold or more) and an initiator were added to the monomer solution. After sparging the reactor with an inert gas, (e.g., nitrogen) and agitating the reaction mixture, the reaction was started and allowed to proceed for two to four hours until substantially all of the monomer had reacted. The resultant mass of wet polymer was then cut into smaller pieces (e.g., 1-2 cm per side), dried in a vacuum or in an inert atmosphere, and then disrupted (e.g., by milling) to produce particles or powder.

[00334] 140 g of acrylic acid was placed into a reactor and diluted with 326 g of deionized water followed by addition of 0.50 g of TMPTA and 0.70 g of a 10% solution of sodium persulfate. The reactor was closed and the reaction mixture was agitated at 250 RPM while argon was bubbled through the reaction mixture. After 70 minutes of bubbling argon, the reaction mixture was heated to produce approximately 4°C increase in temperature per minute. After 7 minutes, the temperature reached approximately 50°C and the entire reaction mixture became a gel that quickly settled to the bottom of the reactor when the agitation was stopped. Heating at 65°C was continued for 2 hours and the gel was allowed to cool overnight. The gel was then cut into pieces and dried in a vacuum oven at 60°C. The resultant mass of polymer was then cut into smaller pieces (e.g., 1-2 cm per side), dried in a vacuum or in an inert atmosphere, and then disrupted (e.g., by milling) to produce particles or powder.

[00335] Alternatively, polycarbophil, a polyacrylic acid crosslinked with divinyl glycol may be used (see, e.g., USP monograph).

[00336] Free-acid forms of crosslinked cation-binding polymers prepared or described according to the present example represent alternative forms of H-CLP. Example 5

[00337] This example describes the preparation of Ca-CLP and Mg-CLP from H-CLP (A. below) and the preparation of Ca-CLP from acrylic acid partially neutralized with a calcium base (B. below). A. Preparation of Ca-CLP and Mg-CLP from H-CLP.

[00338] In an exemplary method for the preparation of Ca-CLP from H-CLP, including, for example, as described in Example 3 or Example 4, polyacrylate with calcium counterions was prepared by adding 60 L of deionized water to a 100L jacketed vessel and then heating to 65°C. An appropriate amount of CaO (for example, 390 g of CaO for preparation of polymer containing 25% calcium counterions) was added slowly with stirring and the mixture stirred to create a solution or suspension. 4 kg of HCLP (for example HCLP prepared by a process substantially similar to Example 3 from NaCLP prepared by process substantially similar to Example 1) was then added to the solution and the mixture stirred at 65°C for four hours. The resulting calcium containing polymer (termed "CaCLP" or "Ca-CLP" herein) was then transferred to drying trays and dried in a tray drier at 100°C until the water content was less than 5%.

[00339] Cross-linked polyacrylate polymers with target levels of 25% magnesium counterions, 10%> calcium counterions, and 25% calcium counterions were prepared from NaCLP manufactured by a process substantially similar to Example 1 followed by enteric coating first with 30 wt% 93F19255 and then 1 wt% YS-1-19025. 352 g of the enteric coated NaCLP polyacrylate particles were washed with 1M sodium bicarbonate and five 10L rinses with water to remove the enteric coating. The water swollen beads were then washed three times with 1 N HC1, with a total of approximately 6 equivalents of acid, twice the number of equivalents of carboxyl groups on the polyacrylate polymer, to convert the polymer to the acid form. The acid was then washed from polymer with four water washes raising the pH from pH 1 to above 3. The total weight of the wet beads was 1782 g. 137g of the wet beads were placed into each of 3 beakers. To produce polyacrylate with approximately 25% magnesium counterions, 1.05g of MgO was placed on the polymer in one beaker, followed by 250 mL deionized water. Similarly, to produce polyacrylate with approximately 10 and 25% calcium counterions 0.58 g of CaO and 1.46g CaO, respectively, were used. The polyacrylate beads were then dried in a vacuum oven. The cation content of each of the dried polyacrylates was measured by ICP using the method in Example 6. The counterion content of the polyacrylates was 25.2% magnesium (target 25% magnesium), 12.0% calcium (10% calcium target) and 24.0% calcium (25% calcium target).

[00340] Alternatively, other calcium or magnesium bases (for example, CaC0₃) may be for preparation of CaCLP from HCLP.

[00341] In an exemplary method, Ca-CLP may be produced from NaCLP. For example a NaCLP with 25% neutralization may be manufactured according to methods of Example 1 or 2, adjusting the procedure to neutralize 25% of the acrylic acid carboxyl groups with NaOH or with Example 1 or 2 and Example 3 using only enough acid in Example 3 to bring the sodium counterions down to a level where they are counterions to 25% of the carboxyl groups. The hydrated 25% NaCLP polymer is then equilibrated with a calcium salt (e.g. CaCl₂) solution to exchange the sodium with calcium. This equilibration may be repeated with fresh solutions of calcium salt to effect more complete exchange with sodium and to remove sodium prior to drying. [00342] In another exemplary method, Ca-CLP including, for example, from about 5% to about 30% Ca-CLP or from about 15% to about 35% Ca-CLP may be produced from calcium polycarbophil (see, e.g., USP monograph) by adding an appropriate amount of acid (e.g., hydrochloric acid, acetic acid, and/or phosphoric acid) to bring calcium counterion to the desired level (e.g., from about 5% to about 30%> Ca-CLP or from about 15% to about 35% Ca-CLP). A water wash may then be used to remove free calcium and the material dried.

B. Preparation of Ca-CLP from acrylic acid partially neutralized with a calcium base.

[00343] In an exemplary method for the preparation of Ca-CLP from acrylic acid partially neutralized with a calcium base, a 25% calcium neutralized crosslinked polyacrylate was prepared as follows: 150 g of acrylic acid was placed into a reactor and diluted with 540 g of deionized water. 25mol%> CaO (mol%> is moles per mole of acrylic acid) was added with stirring and cooling. After dissolution of the CaO, 0.26 mol% TMPTA and 0.091 mol% sodium persulfate were added. The solution was stirred and bubbled with nitrogen and the temperature reduced to 18°C. Sodium ascorbate at 0.022 mol%> was then added and nitrogen purge continued. As the exothermic reaction proceeded, the reactor was heated to 80°C and the reaction was allowed to proceed for two hours. The gel was then cut into pieces and dried in an oven at 80-100°C.

[00344] A 25% calcium neutralized crosslinked polyacrylate was prepared as follows: 13.6g of CaO and 442g of water were placed into a reactor and stirred until all CaO dissolved. The reactor was then cooled to 21°C and 140g of acrylic acid added with stirring. After cooling to 26°C, 0.14g of TMPTA and 0.18g Versenex 80 were added and the solution was deoxygenated with argon sparging. 4.2g of a 10 wt% solution of sodium persulfate and 2.1 g of a 1 wt% solution of tert-butylhydroperoxide were then added. After stirring for 2 minutes 1.05g of a 10 wt% solution of sodium thiosulfate pentahydrate and 0.84g of a 10 wt% solution of sodium erythorbate were added to initiate the polymerization. After the temperature rose to 51°C the reactor was heated at 65°C for 3 hours. The gel was then removed from the reactor, torn and cut into pieces and dried in an oven.

[00345] A 10%) calcium neutralized crosslinked polyacrylate was prepared as follows: 5.4g of CaO, 330 g of water and 140 g acrylic acid were placed into a reactor and stirred for 30 minutes. Then 0.5g of TMPTA and 0.7g of a 10% solution of sodium persulfate were added and the mixture sparged with argon. After stirring for 20 minutes the bath was heated to 85°C. Polymer gel was observed at 55°C (after 7 minutes). The bath temperature was adjusted at 65°C and the reactor heated for 2 hours. The gel was left to cool overnight in the reactor and was then torn into pieces and dried in a vacuum oven. Example 6

[00346] The content (e.g., percentage; %) of certain cations including, for example, calcium, sodium, magnesium, and/or potassium, on a polymer may be determined by ICP- OES, ICP-AES and/or ICP-MS, for example, with a ThermoElectron Finnegan Element 2 or a Perkin Elmer Elan 6000 instrument. The percentage of cations that are counterions to the carboxylate groups in the polymer determined in different ICP measurements may vary by ±20% or less. For example, the determination of 5% to 30% or 15% to 35% calcium and/or magnesium cations as counterions to carboxylate groups in the polymer may vary in different measurements by ICP (e.g., 5% ±20% to 30% ±20% or 15%±20% to 35%±20%).

[00347] For example, the calcium and/or sodium content of a polymer prepared according to Example 5 can be determined by diluting a 250 mg sample of the polymer with 5% nitric acid solution to a total volume of 100 mL. After shaking overnight to extract the calcium and sodium cations from the polymer, an aliquot of the mixture can be diluted with a 1% nitric acid solution as necessary to bring the concentration of the cation within the range of a suitable calibration curve (e.g., a standard curve with a linear range). An appropriate internal standard (e.g., scandium, yttrium, germanium) is used to correct for matrix effects. Samples are diluted to within the range of the linear standard curve for analysis. Preferably the polymer is completely digested. To ensure complete digestion of the sample, an exemplary method is to fully digest the sample in nitric acid (e.g., until the solution becomes clear and colorless), for example by application of heat; using microwave digestion; using other acids or mixture of acids, hydrogen peroxide, or other reagents; or by other methods known in the art. For example, the polymer may be placed in a nitric acid, hydrochloric acid, and hydrogen peroxide medium and microwave digesting the sample using any method known to one of skill in the art. For example, when using ICP-AES with a sample size (e.g., 250 mg), such as with a ThermoElectron Finnegan Element 2 instrument, a 10-fold dilution is used for sodium determinations and a 100-fold dilution is used for calcium determinations. For example, when using ICP-MS, such as with a Perkin Elmer Elan 6000 or a ThemoElement2 instrument, a 10-fold dilution is used for sodium determinations and a 10,000-fold dilution is used for calcium determinations. The final dilution volume should be 10.0 mL to fall within a standard curve generated using standards at 0, 100, 250, 500, 2500, and 5000 ug/L. In order to normalize the results of multiple runs, an internal standard such as scandium or germanium (e.g., about 100 of a 10,000 μg/mL solution of 99.999% scandium oxide in 5% nitric acid) was added to the 10-mL diluted samples before analysis.

[00348] In an exemplary method, a 250.08 mg sample of a polymer prepared according to Example 5 (e.g., Ca-CLP and/or Mg-CLP) was placed in a 100-mL polypropylene tube and a 5% nitric acid solution was added until the total volume of the sample was 100 mL. The tube was then shaken overnight to produce "Mixed Sample A." A 250.1 1 mg sample of the same polymer used to prepare Mixed Sample A was placed in a 100-mL polypropylene tube and a 5% nitric acid solution was added until the total volume of the sample was 100 mL. The tube is then shaken overnight to produce "Mixed Sample B." Next, three 0.100-mL aliquots Mixed Sample A were diluted with a 1% nitric acid solution to final volumes of 10.0 mL. As an internal standard, 102 μί, 101 μΐ_^, and 100 μΐ_^ of a 10,000 μg/mL standard solution of 99.999% scandium oxide in 5% nitric acid was added to the three aliquots, respectively. Separately, three 0.100-mL aliquots of Mixed Sample B were similarly diluted with 1% nitric acid to final volumes of 10.0 mL and doped with 100 μί, 99.0 μί, and 100 μΐ, of the standard scandium solution, respectively. Analysis of calcium content proceeded using a ThermoElectron Finnigan Element 2 ICP-AES instrument (equipped with software version 2.42) according to the manufacturer's specifications. Standards at 0, 100, 250, 500, 2500, and 5000 ug/L were analyzed to generate a standard curve. The six raw calcium concentration measurements (e.g. , 55,449, 55,318, 54,761 , 56,079, 56,375, and 55,949 μ^, respectively) were determined (e.g. , from the standard curve) by normalizing the intensity of the raw calcium measurement to the measurement of the internal scandium standard. These six raw calcium concentration measurements were then converted into weight percent values (e.g. , 5.54, 5.53, 5.48, 5.61 , 5.64, and 5.59 wt.% Ca, respectively) and averaged to provide an overall calcium content of 5.6 wt.%. The percentage of carboxylate groups to which calcium serves as a counterion on a polymer (e.g., the "[x]% Ca-CLP" nomenclature) can be determined from the weight percent calcium measurement (wt.% Ca) by the following equation:

[x]%Ca-CLP = (72.06)(wt.% Ca)/(20.05 -(0.19)(wt.% Ca))

[00349] For this example analysis, therefore, the polymer would be termed "21% Ca- CLP." [00350] For example, polymers of the present disclosure such as crosslinked polyacrylate polymers may have calcium concentration measurements (e.g., average calcium concentration measurements as determined by ICP-AES analysis) of about 13,700 μg of calcium to about 77,300 μg of calcium per gram of the polymer. This range approximately corresponds to a polymer in which calcium serves as a counterion to about 5% to about 30% of the carboxylate groups, as shown in Table 3 below. Alternatively, for example, polymers of the present disclosure such as crosslinked polyacrylate polymers may have calcium concentration measurements (e.g., average calcium concentration measurements as determined by ICP-AES analysis) of about 40,100 μg of calcium to about 89,100 μg of calcium per gram of the polymer. This range approximately corresponds to a polymer in which calcium serves as a counterion to about 15% to about 35% of the carboxylate groups, as shown in Table 3 below.

Table 3 : Calcium Content for Various Exemplary Polyacrylate Polymers.

[00351] Additionally, for example, polymers of the present disclosure such as crosslinked polyacrylate polymers may have magnesium concentration measurements (e.g., average magnesium concentration measurements as determined by ICP-AES analysis) of about 8,400 μg of magnesium to about 48,300 μg of magnesium per gram of the polymer. This range approximately corresponds to a polymer in which magnesium serves as a counterion to about 5% to about 30% of the carboxylate groups, as shown in Table 4 below. Alternatively, for example, polymers of the present disclosure such as crosslinked polyacrylate polymers may have magnesium concentration measurements (e.g., average magnesium concentration measurements as determined by ICP-AES analysis) of about 24,700 μg of magnesium to about 56,000 μg of magnesium per gram of the polymer. This range approximately corresponds to a polymer in which magnesium serves as a counterion to about 15% to about 35% of the carboxylate groups, as shown in Table 4 below.

Table 4:Magnesium Content for Various Exemplary Polyacrylate Polymers.

[00352] Using Mixed Sample A and Mixed Sample B described in the previous paragraph, sodium content was determined by ICP-AES as follows. Three 1.0-mL aliquots of Mixed Sample A were each diluted to a final volume of 10.0 mL using a 1% nitric acid solution. To each was added 1 13 of a 10,000 μg/mL standard solution of 99.999% scandium oxide in 5% nitric acid. Similarly, three 1.00-mL aliquots of Mixed Sample B were diluted to final volumes of 10.0 mL and were doped with 1 15 μί, 1 15 μΐ,, and 1 16 of the standard scandium solution. Analysis of sodium content proceeded using a ThermoElectron Finnigan Element 2 ICP-AES instrument (equipped with software version 2.42) according to the manufacturer's specifications. The six raw sodium concentration measurements (e.g. , 327, 328, 328, 381 , 381 , and 381 μ^, respectively) were determined by normalizing the intensity of the raw sodium measurement to the measurement of the internal scandium standard. These six raw sodium concentration measurements were then averaged (354 μ^) wherein:

354 μg/g is equivalent to 0.035 wt% sodium

[00353] The percentage of carboxylate groups to which sodium serves as a counterion (e.g., the "[x]% Na-CLP" nomenclature) on a polyacrylate polymer can be determined from the weight percent sodium measurement (wt.% Na) by the following equation:

[x]%Na-CLP = (72.06)(wt.% Na)/(23.0 - (0.23)(wt.% Na))

[00354] For this example analysis, with an average sodium concentration of 354 ug of sodium per gram of polyacrylate polymer, or 0.035 wt.% sodium, sodium cations are counterions to about 0.1 1% of the carboxylate groups in the polymer.

[00355] Polymers of the present disclosure may have sodium concentration measurements (e.g. , average sodium concentration measurements as determined by ICP-AES analysis) of about 0 μg of sodium to about 16, 100 μg of sodium per gram of polyacrylate polymer. This range approximately corresponds to a polymer in which sodium serves as a counterion to about 0% to about 5% of the carboxylate groups.

[00356] The percentage of carboxylate groups to which magnesium serves as a counterion on a polymer (e.g., the "[x]% Mg-CLP" nomenclature) can be determined from the weight percent measurement (wt.% Mg) by the following equation:

[x]%Mg-CLP = (72.06)(wt.% Mg)/(12.15 - (0.1 l(wt.% Mg))

[00357] In another exemplary method, the content of certain cations (e.g., calcium, sodium, magnesium, potassium or other cations) on a polyacrylate polymer may be determined by ICP-OES. For example, the calcium content of a polymer prepared according to Example 5 can be determined by diluting a measured mass of polyacrylate polymer with a known volume of a 5% aqueous solution of trace metal grade nitric acid. The sample is then digested by first heating the polyacrylate polymer mixture until gaseous N0₂ is apparent. While continuing to heat, a small measured aliquot of 30-40% hydrogen peroxide is added to the solution. The solution foams and may turn brown. Once the foaming subsides an additional aliquot of hydrogen peroxide is added and repeated until the foaming after hydrogen peroxide addition is minimal, no particulate is visible, and a clear and colorless solution including, for example, a fully digested sample, has been prepared. The total volume of hydrogen peroxide is recorded. Additional measured volumes of 5% nitric acid may be added during the digestion process to maintain an adequate volume of liquid. An appropriate volume of the digested polyacrylate polymer sample is diluted to a final volume of 10 mL with the 5% nitric acid solution to bring the concentration of the cation within the range of a suitable calibration curve; serial dilutions in 5% nitric acid can be made with the total dilution recorded. An internal scandium/cesium standard/ionization buffer was prepared from CsN0₃ and a scandium standard and was used in all analyses to normalize results and correct for matrix effects. The internal standard was prepared by adding 50 mg scandium standard (1000 g/mL) and 1.48 g anhydrous CsN0₃ to 1 L of 5% trace metal grade nitric acid. The internal was mixed with the sample online prior to injection into the ICP instrument. Standard solutions for construction of the standard curve were prepared at 0.2, 1 , 5 and 25 μg/g Ca in 5% nitric acid. Samples were analyzed by ICP- OES on a Perkin Elmer Optima 5300 DV. Ca concentrations in μg/g were determined from the standard curve with correction for dilution, and converted to weight percent as described above.

[00358] In another exemplary method, the content of certain cations (e.g., calcium, sodium, magnesium, potassium or other cations) on a polymer may be determined by ICP- OES using microwave digestion of the sample in a nitric acid, hydrochloric acid, and hydrogen peroxide digestion medium. For example, the calcium content of a polymer prepared according to Example 5 can be determined by placing 50 mg of polymer with 0.800 mL trace metal grade nitric acid, 0.450 mL concentrated trace metal grade hydrochloric acid and 0.200 mL of 30% (w/w) hydrogen peroxide in a digestion vessel. The vessel is then placed in a MARS 5 (CEM Corp) microwave at 100% power for 2 minutes (to a temperature of 165°C) followed by 3 minutes at 100% power (to a temperature of 175°C) and then holding the sample at 175°C for 10 minutes to digest the sample including, for example, to completely digest the sample. The digested polymer sample is then diluted to a final volume of 50 mL with purified water to bring the concentration of the cation within the range of the standard curve. Standard solutions for construction of the standard curve were prepared at 0 (blank), 100, 500 and 1000 ug/mL Ca in 4% (v/v) nitric acid. An internal standard solution was prepared containing 20 μg/mL yttrium and 100 μg/mL germanium in 4% trace metal grade nitric acid. The internal standard was used in all analyses to normalize results and correct for matrix effects. Samples were analyzed on a Thermo Electron iCAP 6000 ICP-OES. Ca concentrations in μg/g were determined from the standard curve with correction for dilution, and converted to weight percent as described above.

[00359] Likewise, sodium content in the same sample was analyzed by placing 50 mg of polymer with 0.800 mL trace metal grade nitric acid, 0.450 mL concentrated trace metal grade hydrochloric acid and 0.200 mL of 30%> (w/w) hydrogen peroxide in a digestion vessel. The vessel is then placed in a MARS 5 (CEM Corp) microwave at 100% power for 10 minutes (to a temperature of 185°C) followed by 5 minutes at 100%) power (to a temperature of 195°C) and then holding the sample at 195°C for 15 minutes to digest the sample. The digested polymer sample is then diluted to a final volume of 50 mL with purified water to bring the concentration of the cation within the range of the standard curve. Standard solutions for construction of the standard curve were prepared at 0 (blank), 0.1 , 0.5 and 1.0 μg/mL Na in 4% (v/v) nitric acid. Example 7

[00360] The effect of % calcium-CLP on the adhesion including, for example, bioadhesion, of hydrated polymer and on morphology of the dried CaCLP particles was assessed.

[00361] For these studies, H-CLP is prepared, for example, as described in Examples 1 and 3. Calcium oxide was then added to each sample in the amount shown in Table 3 to achieve degrees of % calcium-CLP, e.g., 5 to 40%. After equilibration with stirring excess solution was drained from the Ca-CLP. The hydrated polymer was used for adhesiveness determinations.

[00362] To determine actual %Ca substitution versus target %Ca substitution, samples of each calcium loaded bead preparation were placed in glass beakers and dried in a vacuum oven. These samples were analyzed for calcium content using an Inductively Coupled Plasma optical emission spectroscopy (ICP-OES) method, for example, as described in Example 6. Actual %Ca substitution versus target %Ca substitution is shown in Table 5.

Table 5. Ca-CLP Sample Preparation Summary

[00363] The adhesiveness of the Ca-CLP samples was assessed using several substrates including, skin, glass, and steel. The adhesion results are summarized in Table 6. In the hydrated state, 0% Ca-CLP (H-CLP) was adhesive to skin, glass, and steel. In contrast, 10% to 40%) Ca-CLP was not adhesive to skin, glass, and steel. Table 6. Adhesiveness of CaCLP in Hydrated Stage vs. Degree of Ca Substitution

[00364] The morphology and adherence of dried CaCLP particles, with varying degree of calcium substitution was determined. Wet CLP particles were placed in glass beakers to dry in a vacuum oven. The morphology and adhesion to glass were assessed versus the degree of calcium substitution. Below 1 1% calcium substitution some CLP particles adhered so tightly to the glass that they could not be removed with a spatula. Below 24%o calcium substitution firm pressure was required to remove some of the CLP particles from the surface. Between 24 and 32% calcium substitution some CLP particles adhered to the glass but could be dislodged with slight pressure. Above 32% calcium substitution none of the CLP particles adhered to the glass. In the dried state, the H-CLP CLP particles with up to 18% calcium substitution formed hard clumps while all samples with 24% calcium substitution and above formed individual particles. Example 8

[00365] The saline holding capacity of a cross-linked polyelectrolyte polymer, such as a cross-linked polyacrylate polymer, may be determined by known methods in the art.

[00366] In an exemplary method, saline holding capacity for H-CLP was determined with a 0.15 M sodium phosphate buffered solution as follows. A pH seven buffer of sodium phosphate tribasic (Na₃P0₄ ^»12H₂0; MW 380.124) was prepared by dissolving 19.0062 grams in about 950 milliliters pure water and adjusting the pH to a final pH of 7 ± 0.1 with IN HC1 before final dilution to one liter resulting in a solution with a sodium concentration of 0.15 M. Next, an amount of cross-linked cation-binding polyelectrolyte, for example, cross-linked polyacrylate CLP particles (e.g., HCLP prepared according to Examples 1-4) (e.g., 0.1 + 0.025 grams), were transferred to a tared filter tube and the mass of the polymer was recorded as in Wl . Next, the tube was returned to the balance to record the weight of the tube plus the sample as W2. An excess (e.g., more than seventy times the mass of polymer) amount of the pH 7.0 buffer (e.g., ten milliliters) was then transferred to the tube containing the CLP sample. The tube was then placed on a flat bed shaker with shaking for two, four or six hours. After shaking, all excess fluid was removed from the tube (e.g., no visible fluid in the tube). Last, the tube and sample were weighed and recorded as W3. The saline holding capacity (SHC) was calculated by dividing the mass of the fluid absorbed by the mass of the dry crosslinked polyacrylate polymer, for example, SHC (g/g) = (W3-W2)/ (Wl). According to the present disclosure, cross-linked cation-binding polymers, including polyacrylate CLP particles prepared according to the methods disclosed herein, had a saline holding capacity of 20 g/g, 30 g/g, 40 g/g, or more. Alternatively stated, such cross-linked cation-binding polymers, including where the polyelectrolyte is polyacrylate, can absorb 20- fold, 30-fold, 40-fold, or more of their mass in a saline solution.

Example 9

[00367] The saline holding capacity of a cross-linked polyelectrolyte polymer, such as a cross-linked polyacrylate polymer, may be determined by known methods in the art.

[00368] In an exemplary method, a saline absorption capacity (e.g., saline holding capacity) for salts of cross-linked cation-binding polyelectrolyte, for example cross-linked polyacrylate salts of CLP is determined by first rinsing the polymer with hydrochloric acid to convert the salt form to the acid form. The saline absorption capacity (e.g., saline holding capacity) of the acid form is then determined.

[00369] For example the saline absorption capacity (e.g., saline holding capacity) of CaCLP particles can be determined as follows. Phosphate equilibration buffer of 50 mM phosphate, 154 mM NaCl was prepared by dissolving 19.5 g trisodium phosphate dodecahydrate (Na₃PC>4 · 12H₂0, molecular weight 380.12) in approximately 950 mL of deionized water with pH adjustment to 7.0 with IN HCl and then diluting to a final volume of 1000 mL with deionized water. A disposable polypropylene chromatography tube was weighed and then 0.1 g of CaCLP particles were transferred to the tube and reweighed. 10 mL IN HCl was added to the tube containing the sample and the tube was placed on a flat bed shaker and shaken for 30 minutes. The fluid was drained from the tube by gravity. Another 10 mL of IN HCl was transferred into the tube and shaken for another 30 minutes. The fluid was drained from the tube by gravity. Another 10 mL of IN HCl was transferred to the tube and shaken for 60 minutes. The fluid was drained from the tube by gravity. 10 mL of deionized water was transferred to the tube and the water immediately suctioned off using a vacuum flask and vacuum pump or a faucet-mounted water aspirator, until there was no visible fluid in the tube. This water rinse step was repeated two more times. 10 milliliters of the pH 7.0 phosphate buffer was transferred to the tube and shaken for 15 minutes. Using a vacuum flask and vacuum pump, or a faucet-mounted water aspirator, the fluid that was not absorbed into the CLP particles was suctioned off so that there was no visible fluid in the tube. 10 mL of the pH 7.0 phosphate buffer was transferred to the tube and the polymer was permitted to swell for 30 minutes then fluid suctioned off until there was no visible fluid in the tube. This was repeated twice with 15 minute swell times and then with a 3 hour swell time so that the total swelling time was four hours. After suctioning off the fluid the tube with swollen polymer was weighed.

[00370] The amount of phosphate buffered saline absorbed by the polymer was determined by subtracting the original weight of the tube with dry polymer from the weight of the tube with swollen polymer.

[00371] The saline absorption capacity (e.g., saline holding capacity) was determined by dividing the amount of saline absorbed by the polymer by the weight of the polymer used in the test (g/g CLP).

Example 10

[00372] The saline holding capacity of a cross-linked polyelectrolyte polymer, such as a cross-linked polyacrylate polymer, may be determined by known methods in the art.

[00373] In an exemplary method, a saline absorption capacity (e.g., saline holding capacity) of crosslinked cation-binding polymers comprising monomers containing carboxyate groups, wherein the polymers further comprise calcium and/or magnesium cations (e.g., calcium cations or magnesium cations or a mixture thereof), wherein the calcium and/or magnesium cations are counterions to the carboxylate groups in the polymer is measured using a centrifugal method. According to this method, the centrifuge retention capacity (CRC) of the polymer (e.g., Ca-CLP or Mg-CLP) is determined without first treating the polymer with acid.

[00374] For example the saline holding capacity of Ca-CLP particles may be determined. A pH 7 phosphate buffered saline uptake buffer is prepared with 10.65 g of sodium phosphate dibasic (anhydrous) in 1 L purified water, with pH adjustment to pH 7.0 with IN HC1. The weights of a centrifuge tube is determined (Wtube). 100 ±10 mg of the Ca-CLP particles are weighed and added to centrifuge tube and the tube reweighed (Wtube+sample). 25 mL of uptake buffer is then added to centrifuge tube and the tube capped and shaken vigorously. The tube is then shaken on a wrist-action shaker for at least 8 hours. The tube is then centrifuged for 10 minutes at 3500 rpm and the supernatant decanted. The tube with the swollen gel particles is reweighed (Wtube+swollen gel) and the saline holding capacity determined as:

[00375] Saline holding capacity (w/w) = (Wt(tube+swollen gel) - W(tube) ) / (W(tube+sample) - W(tube)). Example 11

[00376] This example describes the effects of H-CLP, e.g., prepared as described in Examples 1 and 3, and CaCLP (prepared by addition of calcium counterions to CLP during manufacture, e.g., as described in Examples 5 and 7) on fecal and urinary ion excretion and fecal mass in rats.

[00377] In an exemplary study, Ca-CLP with calcium added as counterions during manufacturing at levels as described in Table 7 were prepared using the methods described in Example 5 and 7 including drying in a vacuum oven. Each of these CaCLP polymers were tested in groups of six rats to determine the effect of the percent calcium on the CaCLP on the fecal excretion of Na and K and on the mass of feces excreted.

Table 7. CLP Forms Manufactured

[00378] Ca-CLP was prepared as described in Examples 5 and 7 with drying in a vacuum oven. The mixture was stirred and left to react overnight at room temperature. The mixture was then placed into a vacuum oven and heated at approximately 60°C. [00379] Ca-CLP or H-CLP was mixed at a level of 5% into pulverized LabDiet 5012 and the mixture was processed through a food blender several times until the food/CLP powder was uniform in color and size. Daily measurements of rat weight and 24-hour food intake, water intake, urine output, and fecal output were recorded. Dosing started on Day 1. On Days 4, 5 and 6 24-hour feces and urine were collected for ICP-AES analysis of fecal Na, fecal K and urine P. Samples were digested for ICP-AES analysis by placing the sample in flask, adding an aqueous solution of 5% trace metal grade concentrated nitric acid, and heating to boiling. 30% hydrogen peroxide was then added in small aliquots until the solution was clear and vigorous foaming from addition of hydrogen peroxide had ceased. The digested samples were analyzed by ICP/AES (inductively coupled plasma atomic emission spectroscopy) for fecal sodium, fecal potassium, and urinary phosphate. Changes in fecal sodium and potassium excretion levels from control (rats on rat chow and no polymer) were calculated (i.e., control fecal sodium was subtracted from fecal sodium in the treatment groups).

[00380] As shown in Table 8, fecal sodium excretion was relatively independent of the percentage of calcium counterions on the CLP until a decrease between 34-42%. With and an approximately linear decrease from 42 to 71% while Fecal K decreased approximately linearly between 0-40%Ca-CLP and then remained relatively constant.

[00381] The ffect of different amounts of calcium counterion on Ca-CLP on daily urinary phosphorus (P) excretion and fecal massare also shown in Table 6 as change from control ((i.e., control urinary phosphorus excretion levels were subtracted from urinary phosphorus levels from treatment groups).

[00382] Urinary phosphorus declined in an approximately linearly with was percent calcium counterion on Ca-CLP. Urinary excretion of phosphorus is a measure of the acid/base status of the rat with increasing urine phosphorus correlating with a shift to a more acidic state.

[00383] The effect of the percent calcium counterion on Ca-CLP on fecal weight was determined and the change from control daily fecal weights are shown in Table 8 (i.e., control fecal weight was subtracted from fecal weights in treatment groups). Fecal weight was approximately constant between 0 and 31%Ca-CLP. Between 31 and 42%CaCLP the fecal weight dropped significantly and then became approximately constant to 71%CaCLP. Table 8. Change From Control in Daily Fecal Sodium, Fecal Potassium, Urinary Phosphorous, and Fecal Weight in Rats Administered H-CLP or Ca-CLP

Example 12

[00384] This example describes the effects of H-CLP (e.g., prepared as described in Examples 1 and 3) and CaCLP (e.g., prepared by addition of calcium counterions to CLP during manufacturing as described in Examples 5 and 7) with and without added CaC0₃ on fecal and urinary ion excretion and fecal mass in rats.

[00385] In this exemplary study, the effect of Ca-CLP or H-CLP with or without calcium carbonate base (administered as TUMS®) on the fecal excretion of Na and K, fecal mass, and urinary excretion of P was studied in rats comparing CLP neutralization by calcium added during manufacturing (6.9%CaCLP or 25%CaCLP) and by CaC0₃ mixed into the feed as Turns (0 to 0.75 equivalents). 6.9%CaCLP and 25%CaCLP were manufactured using the method of Example 9 with vacuum drying of the CLP particles.

[00386] Multiple groups of 6 rats were fed diets containing CLP (H-CLP, 6.9%Ca-CLP, or 25%CaCLP) mixed with TUMS® (0 to 0.75 equivalents of calcium carbonate) as 5w/w% of their daily diet. Each group received a different treatment as described in Table 9. The diet was prepared by mixing Ca-CLP or H-CLP, TUMS® where required, and pulverized LabDiet 5012 and then processing the mixture with a food blender several times until the powder was uniform in color and size.

[00387] Daily measurements of rat weight, food intake, water intake, urine output, and fecal output were recorded. Dosing started on Day 1. On days 4, 5, and 6 24-hour feces and urine were collected for ICP-AES analysis of fecal Na, fecal K and urine P. Samples were digested for ICP by placing each sample into a flask, adding an aqueous solution of 5% trace metal grade concentrated nitric acid, and heating to boiling. 30% hydrogen peroxide was then added in small aliquots until the solutions were clear and the vigorous foaming after additions of hydrogen peroxide had ceased. The digested samples were analyzed by ICP for fecal sodium, fecal potassium, and urinary phosphate. Changes in excretion over control (rats on rat chow and no polymer) fecal sodium, and potassium excretion levels were calculated and are shown in Table 9 below (i.e., control fecal sodium and potassium excretion levels were subtracted from fecal sodium and potassium levels from treatment groups).

[00388] As shown in Table 9, Administration of CLP with and without base increased fecal excretion of both sodium and potassium compared to control for all formulations tested. Increasing the degree of CLP neutralization had no significant effect on fecal sodium excretion whereas fecal potassium excretion decreased approximately linearly with increases in neutralization. Neutralization of CLP by addition of calcium counterions at 6.9% and 25% during manufacture and/or by addition of CaC03 had similar effect on fecal sodium and potassium excretion and on urinary P excretion.

[00389] As shown in Table 9, co-administration of HCLP or CaCLP with base decreased urinary phosphorous levels. Urinary excretion of phosphorus is a measure of the acid/base status of the rat with increasing urine phosphorus correlating with a shift to a more acidic state. When H-CLP was administered without base high urinary phosphorous values were observed. When H-CLP or Ca-CLP was administered with increasing amounts of CaC0₃ base theurinary excretion of phosphorus was decreased and in the range of 65 to 72% base the urinary phosphorus was not different from controls. Neutralization of CLP by addition of calcium counterions at 6.9% and 25% during manufacture and/or by addition of CaC03 had similar effect on urinary P excretion.

Table 9. Effect of Added CaC0₃ on Daily Fecal Sodium and Potassium Excretion and Urinary Phosphorous Excretion in Rats Administered HCLP or CaCLP

Base added Total CLP

Fecal Na Fecal K Urinary P

CLP as CaC03 Carboxyl

Excretion Excretion Excretion Form (Equivalent Neutralization¹

(mg/d) (mg/d) (mg/d) Ratio) (%)

H-CLP .62 62 27.5 35.8 4.5

6.9%CaCL

P 0 6.9 28.9 78.7 22.6

6.9%CaCL

P .65 71.9 31.1 18.8 -2.8

25%CaCL

P 0 25 22.7 53.3 13.9

25%CaCL

P .4 65 23.2 33.9 0.9

25%CaCL

P .50 75 20.8 22.3 -5.3

Total carboxyl neutralization is the sum of the percent of Ca counterions added during manufacturing and the equivalents of base mixed into the feed.

[00390] The addition of CaC0₃ to the rat feed decreases the fecal excretion of sodium and potassium. At an equivalent total CLP neutralization ratio fecal sodium and potassium excretion and urinary P excretion were similar regardless of whether the neutralization was from calcium base added during manufacture or calcium base added as CaC0₃ (Turns^®).

[00391] A comparison of the data in Examples 11 and 12 show that for low levels of total neutralization (0 to about 30-35%), base added as CaC0₃ or base added as counterions during manufacture had similar effects on fecal sodium and potassium excretion. At higher levels of calcium counterions added during manufacture (from approximately 30- 35%CaCLP to 71%CaCLP), fecal excretion of sodium and potassium decreased to a greater extent than for the same total neutralization of CLP obtained with HCLP, 6.9%CaCLP or 25%CaCLP with added CaC0₃. The effect of neutralization of urinary phosphorus excretion did not depend whether the calcium counterions were added during manufacture or base was mixed into the formulation as CaC0₃.

[00392] Changes in fecal weight compared to control are shown in Table 10 (control fecal weight was subtracted from fecal weight in the treatment groups). Table 10. Effect of Added CaC0₃ on Daily Fecal Excretion in Rats Administered 0-25% CaCLP

l^rTotal carboxyl neutralization is the sum of the percent of Ca counterions added during manufacturing and the equivalents of base mixed into the feed.

[00393] A comparison of the data in Examples 11 and 12 is provided in Table 11 for ease of comparison. At low levels of reacted calcium (0 to about 30-35%) on the polymer, base added as CaC03 or calcium counterions added during manufacturing had similar effects on fecal sodium and potassium excretion. At higher levels of calcium counterions added during manufacturing (about 30-35%) to 75%) fecal excretion of sodium and potassium were decreased compared to mixtures of CaC0₃ with low levels of reacted Ca + CaC0₃ or H- CLP. Base added as CaC03 or calcium counterions added during manufacturing had similar effects on urinary P excretion.

Table 11. Comparison of Fecal Na and K Excretion from Tables 8 and 9 for for Total

CLP Carboxyl Neutralization Between 31 and 75% Neutralization

^otal carboxyl neutralization is the sum of the percent of Ca counterions ac ded during manufacturing and the equivalents of base mixed into the feed. Example 13

[00394] An open-label clinical trial was performed in twelve healthy human subjects.

Each patient received an equivalent of 15 g H-CLP/day as either 25%CaCLP (n=6) or

60%CaCLP (n=6), divided into three doses, administered one hour prior to meals. Subjects remained in the clinical research unit for the duration of the study.

[00395] 25%CaCLP and 60%CaCLP were prepared according to Example 5. After cation exchange to load the polyacrylate with calcium, the polymer was milled to break up the bead structure and reduce the particle size. The CaCLP powder was mixed into pudding immediately prior to dosing. The subjects were required to eat the entire pudding aliquot.

[00396] The clinical trial evaluated whether administration of CaCLP when compared to a baseline period (1) altered fecal excretion of sodium, potassium, or phosphorous (2) altered measures of acidosis including serum total bicarbonate, urine pH and urine phosphorus, (3) altered serum potassium levels and (4) altered fecal weight.

[00397] After a 5 day baseline period, CaCLP was administered in pudding, 3 times a day for a total of 7 days (a total of 14 doses). For 25%CaCLP the dose was 16 g (5.33g tid). For 60% CaCLP the dose was 18g (6g tid). A dose of 16g of 25%CaCLP and 18g 60%CaCLP each delivered an equivalent number of moles of cation exchange carboxyl groups as 15g of H-CLP (208 mEq).

[00398] Diet was controlled with all participants having identical meals. Subjects were requested to consume all of their meals.

[00399] Subjects fasted for at least eight hours at screening and four hours at admission prior to the collection of blood and urine samples for clinical laboratory tests. Fasting was not required prior to collection of urine and blood samples taken during the study. Water ad libitum was allowed during the periods of fasting. [00400] Twenty four hour daily stool and urine samples were collected daily and evaluated for stool weight, fecal electrolytes, urine pH, and urine phosphorus. Daily serum samples were evaluated for serum potassium and total bicarbonate. Fecal samples were evaluated by ICP for the concentration of sodium, potassium, calcium and magnesium. All urine specimens were collected and volume recorded. Urine samples were pooled for each 24-hour period and an aliquot sampled for sodium, potassium, calcium, phosphorous and magnesium analysis.

[00401] Daily parameters for the treatment period were compared to baseline, with daily parameters for days 3-6 averaged and compared to the average for treatment days 10-13. The average change from baseline in fecal excretion of sodium and potassium are shown in Table 12. An increase in percent calcium counterion from 25 to 60% resulted in a decrease in fecal sodium and potassium excretion and a larger drop in serum potassium.

Table 12: Average change from baseline in fecal sodium, fecal potassium and serum

[00402] Measures of acidosis included urine pH, total serum C0₂, and urine phosphate. The average change from baseline in these parameters for Days 7-13 are shown in Table 13. The change from baseline in serum bicarbonate and urine pH were similar for 25%CaCLP and 60%CaCLP. The urinary phosphorus excretion decreased by a factor of 10 with an increase from 25% to 60% calcium counterion. This was paralleled by a decrease in fecal phosphorus excretion by a factor of 10 between 25% and 60% calcium counterion.

Table 13. Avera e Chan e from Baseline in Acidosis Parameters for Da s 7-13

[00403] Administration of CaCLP led to an increase in fecal weight as shown in Table 14. This increase in fecal weight was not associated with diarrhea but is expected to be due to water entrapped in the superabsorbent polymer. An increase in the percent of calcium counterion from 25 to 60% decreased the fecal weight.

Table 14. Avera e Chan e from Baseline in Fecal Weight for Days 7-13

Example 14

[00404] An open-label clinical trial was performed in twenty four healthy human subjects. Each patient received an equivalent of 15 g H-CLP/day as either 25%CaCLP or 50%CaCLP, divided into three doses, administered one hour prior to meals. Subjects remained in the clinical research unit for the duration of the study.

Table 15. Dose Groups

25%CaCLP is H-CLP with 25% of the carboxyl groups reacted with calcium base; 50%> CaC03 is CaC03 added to the formulation at a mass that will neutralize 50% of the carboxyl groups in an equivalent dose of H-CLP.

²A11 CLP doses gave an equivalent dose of carboxyl groups as 15g of H-CLP

[00405] 25%CaCLP and 50%CaCLP were prepared according to Example 5. After cation exchange to load the polyacrylate with calcium, the polymer was milled to break up the bead structure and reduce the particle size. The CaCLP powder was mixed into pudding immediately prior to dosing. The subjects were required to eat the entire pudding aliquot. [00406] The clinical trial evaluated whether administration of CLP when compared to a baseline period (1) altered fecal excretion of sodium, potassium or phosphorus (2) altered measures of acidosis including serum total bicarbonate, urine pH and urine phosphorus, (3) altered serum potassium levels, and (4) altered fecal weight.

[00407] After a 5 day baseline period, CLP was administered in capsules with water or in pudding, twice a day (before breakfast and before dinner) for a total of 7 days (a total of 14 doses) as shown in Table 15. Groups 1 and 3 had the CLP formulation administered in capsules with water and Groups 2 and 4 had the CLP formulation mixed into pudding immediately prior to administration. All groups were administered an equivalent number of moles of cation exchange carboxyl groups as 15 g of H-CLP (208 mEq).

[00408] Diet was controlled with all participants having identical meals. Subjects were requested to consume all of their meals.

[00409] Subjects fasted for at least eight hours at screening and four hours at admission prior to the collection of blood and urine samples for clinical laboratory tests. Fasting was not required prior to urine and blood samples taken during the study. Water ad libitum was allowed during the periods of fasting.

[00410] Twenty four hour daily stool and urine samples were collected daily and evaluated for stool weight, fecal electrolytes, urine pH, and urine phosphorus. Daily serum samples were evaluated for serum potassium and total bicarbonate. Fecal samples were evaluated by ICP for the concentration of sodium, potassium, calcium, and magnesium. All urine specimens were collected and volume recorded. Urine samples were pooled for each 24-hour period and an aliquot sampled for sodium, potassium, calcium, phosphorous, and magnesium analysis.

[00411] Daily parameters for the treatment period were compared to baseline, with daily parameters for days 3-6 averaged and compared to the average for treatment days 10-13. The average change from baseline in fecal excretion of sodium and potassium are shown in Table 16. All groups had an increase in fecal sodium and potassium excretion compared to baseline. Table 16: Average change from baseline in fecal sodium, fecal potassium and serum

²A11 CLP doses gave an equivalent dose of carboxyl groups as 15g of H-CLP

[00412] Measures of acidosis included urine pH, total serum C0₂ and urine phosphate. The average change from baseline in these parameters for Days 7-13 are shown in Table 17.

¹25%oCaCLP is H-CLP with 25% of the carboxyl groups reacted with calcium base; 50% CaC03 is CaC03 added to the formulation at a mass that will neutralize 50% of the carboxyl groups in an equivalent dose of H-CLP.

²A11 CLP doses gave an equivalent dose of carboxyl groups as 15g of H-CLP

[00413] Administration of CLP led to an increase in fecal weight as shown in Table 18. This increase in fecal weight was not associated with diarrhea but is expected to be due to water entrapped in the superabsorbent polymer. Table 18. Average Change from Baseline in Fecal Weight for Days 7-13

¹25%CaCLP is H-CLP with 25% of the carboxyl groups reacted with calcium base; 50% CaC03 is CaC03 added to the formulation at a mass that will neutralize 50% of the carboxyl groups in an equivalent dose of H-CLP.

2A11 CLP doses gave an equivalent dose of carboxyl groups as 15g of H-CLP

Example 15

[00414] This example demonstrates the treatment of heart failure patients with a cross- linked polyelectrolyte polymer such as a crosslinked cation-binding polymer comprising monomers that comprise carboxylic acid groups (e.g., crosslinked polyacrylic acid polymer such as Ca-CLP).

[00415] In an exemplary method, patients with heart failure including, for example heart failure associated with chronic kidney disease (e.g., patients classified as class III or IV according to the New York Heart Association Classification scheme shown in table 19 below) are treated with Ca-CLP (e.g., a cross-linked polyacrylic acid polymer that comprises calcium cations, and wherein the calcium cations are counterions to about 5% to about 30%) or about 15% to about 35% of the carboxylate groups in the polymer, including, for example, 25% Ca-CLP.

[00416] Serum chemistry, clinical signs and symptoms of heart failure, urinary electrolytes, thirst evaluation and other assessments may be evaluated throughout the treatment. Assessments which evaluate signs and symptoms of heart failure include the New York Heart Association Class (as shown in Table 19), changes in dyspnea as assessed by the patient's response to a single question using responses on a Likert scale ranging from "much worse" to "much better," the six minute walk test and a patient reported outcome instrument (Kansas City Cardiomyopathy Questionnaire). Dyspnea may be evaluated using a quantitative patient self-assessment of breathing status compared to baseline with answers on a 7-point Likert scale ranging from "much worse" to "much better." Additionally, the six-minute walk test is a well-accepted measure of heart failure status, with patients able to walk shorter and shorter distances as heart failure progresses. Further, the Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific instrument for measuring health related quality of life in patients with congestive heart failure. The scale for each of the quality of life parameters is 0 to 100, with 100 being the best quality of life. Fluid status may also be evaluated by total body weight and extremity edema. Additionally, mean total serum C0₂ and serum bicarbonate may be measured as a measure of acid/base status. Table 19: New York Heart Association Classification of Heart Failure Patients

[00417] Treatment with Ca-CLP results in significant and clinically meaningful improvement of signs and symptoms in NYHA class III/IV heart failure patients including, for example, a reduction in NYHA class (e.g. , a reduction in class from IV or III to II or I) a reduction of body weight, improvement in subjective symptoms (dyspnea) and quality of life (Kansas City Cardiomyopathy Questionnaire scores), and improvements in objective measures of physical function (6 Minute Walk Test) and clinical signs and symptoms (NYHA Classification; extremity edema) without resulting in a change in the subject's acid/base status.

[00418] While the present disclosure has been described and illustrated herein by references to various specific materials, procedures and examples, it is understood that the disclosure is not restricted to the particular combinations of materials and procedures selected for that purpose. Numerous variations of such details can be implied as will be appreciated by those skilled in the art. It is intended that the specification and examples be considered as exemplary only, with the true scope and spirit of the disclosure being indicated by the following claims. All references, patents, and patent applications referred to in this application are herein incorporated by reference in their entireties.

Claims

CLAIMS What is claimed is:

1. A crosslinked cation-binding polymer comprising:

a. monomers comprising carboxylate groups; and b. calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 5% to about 30% of the carboxylate groups in said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups in said polymer.

2. A crosslinked cation-binding polymer comprising:

a. monomers comprising carboxylate groups; and b. calcium and/or magnesium cations, wherein the calcium and/or magnesium cations are counterions to about 15% to about 35%) of the carboxylate groups in said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups in said polymer.

3. The polymer of any one of claims 1 or 2, wherein said calcium and/or magnesium cations are counterions to about 20% to about 30% of the carboxylate groups in said polymer.

4. The polymer of any one of claims 1 or 2, wherein said calcium and/or magnesium cations are counterions to about 21% of the carboxylate groups in said polymer.

5. The polymer of any one of claims 1 or 2, wherein said calcium and/or magnesium cations are counterions to about 22% of the carboxylate groups in said polymer.

6. The polymer of any one of claims 1 or 2, wherein said calcium and/or magnesium cations are counterions to about 25% of the carboxylate groups in said polymer.

7. The polymer of any one of claims 1 or 2, wherein said calcium and/or magnesium cations are counterions to about 29% of the carboxylate groups in said polymer.

8. The polymer of claim 1, wherein said calcium and/or magnesium cations are counterions to about 5% to about 10%>, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%o, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in said polymer.

9. The polymer of claim 2, wherein said calcium and/or magnesium cations are counterions to about 15% to about 20%, about 15% to about 25%, about 15% to about 30%), about 15% to about 35%, about 20% to about 25%, about 20% to about 30%), about 20%) to about 35%, about 25% to about 30%, or about 25% to about 35%) of the carboxylate groups in said polymer.

10. The polymer of any of claims 1-9, wherein said calcium and/or magnesium cations consist of calcium cations.

11. The polymer of any one of claims 1 or 2, wherein counterions that are not calcium, magnesium, or sodium are hydrogen.

12. The polymer of any of claims 1-11, wherein the counterions to said carboxylate groups consist of said calcium and/or magnesium counterions, and hydrogen counterions.

13. The polymer of any of claims 1-12, wherein said monomer is acrylic acid, an acrylic acid derivative, or a salt thereof.

14. The polymer of claim 13, wherein said monomer is acrylic acid or a salt thereof.

15. The polymer of any of claims 1-14, wherein said polymer is crosslinked with a crosslinker selected from diethelyeneglycol diacrylate (diacryl glycerol), triallylamine, tetraallyloxyethane, allylmethacrylate, 1,1,1-trimethylolpropane triacrylate (TMPTA), divinyl benzene, and divinyl glycol.

16. The polymer of claim 15, wherein said crosslinked polymer is derived from acrylic acid monomers and TMPTA.

17. The polymer of any of claims 1-16, wherein said polymer has an in vitro saline absorption capacity of at least about 20 times its weight.

18. The polymer of any of claims 1-16, wherein said polymer has an in vitro saline absorption capacity of at least about 30 times its weight.

19. The polymer of any of claims 1-16, wherein said polymer has an in vitro saline absorption capacity of at least about 40 times its weight.

20. The polymer of any one of claims 1 or 2, wherein no less than about 70% of said base has a particle size of about 212 microns to about 500 microns.

21. The polymer of any one of claim 1 or 2, wherein no less than about 70% of said base has a particle size of about 75 microns or less.

22. A composition comprising:

a. the polymer of any of claims 1-21; and b. optionally an additional base.

23. The composition of claim 22, wherein said base is present in an amount sufficient to provide from about 0.2 equivalents to about 0.9 equivalents of base per equivalent of carboxylic acid groups in said polymer.

24. The composition of claim 22, wherein said base is present in an amount up to about 0.8 equivalents of base per equivalent of carboxylic acid groups in said polymer.

25. The composition of any of claims 22-24, wherein said polymer comprises calcium cations that are counterions to about 20% to about 30% of the carboxylic acid groups in the polymer and the base is present in an amount sufficient to provide about 0.35 to about 0.5 equivalents of base per equivalent of carboxylic acid groups in said polymer.

26. The composition of any of claims 22-24, wherein said polymer comprises calcium cations that are counterions to about 25% of the carboxylic acid groups in the polymer and the base is presence in an amount sufficient to provide about 0.5 equivalents of base per equivalent of carboxylic groups in said polymer.

27. The composition of any of claims 22-26, wherein said base is a pharmaceutically acceptable base, a salt thereof, or a combination thereof.

28. The composition of claim 27, wherein the base is selected from an alkali metal hydroxide, an alkali metal acetate, an alkali metal carbonate, an alkali metal bicarbonate, an alkali metal oxide, an alkaline earth metal hydroxide, an alkaline earth metal acetate, an alkaline earth metal carbonate, an alkaline earth metal bicarbonate, an alkaline earth metal oxide, an organic base, choline, lysine, arginine, histidine, an acetate, a butyrate, a propionate, a lactate, a succinate, a citrate, an isocitrate, a fumarate, a malate, a malonate, an oxaloacetate, a pyruvate, a phosphate, a carbonate, a bicarbonate, a benzoate, an oxide an oxalate, a hydroxide, an amine, a hydrogen citrate, calcium bicarbonate, calcium carbonate, calcium oxide, calcium hydroxide, magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium bicarbonate, aluminum carbonate, aluminum hydroxide, sodium bicarbonate, potassium citrate, and combinations thereof.

29. The composition of any of claims 22-28, wherein said polymer has an in vitro saline absorption capacity of at least about 20 times its weight.

30. The composition of any of claims 22-28, wherein said polymer has an in vitro saline absorption capacity of at least about 30 times its weight.

31. The composition of any of claims 22-28, wherein said polymer has an in vitro saline absorption capacity of at least 40 times its weight.

32. The composition of any of claims 22-31, wherein said polymer is a polyacrylate polymer.

33. The composition of any of claims 22-32, wherein said polymer is crosslinked with TMPTA.

34. The composition of any of claims 22-33, wherein the base is calcium carbonate.

35. A composition comprising :

a. a crosslinked polyacrylate polymer comprising acrylic acid repeat units that comprise carboxylic acid groups, and calcium and/or magnesium cations, wherein said calcium cations are counterions to about 5% to about 30% of the carboxylate groups in said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups in said polymer; and b. calcium carbonate.

A composition comprising:

a. a crosslinked polyacrylate polymer comprising acrylic acid repeat units that comprise carboxylic acid groups, and calcium and/or magnesium cations, wherein said calcium cations are counterions to about 15% to about 35% of the carboxylate groups in said polymer, and wherein the polymer comprises no more than about 5% sodium cations as counterions to the carboxylate groups in said polymer; and b. calcium carbonate.

The composition of any one of claims 35 or 36, wherein said calcium and/or magnesium cations are counterions to about 20% to about 30% of the carboxylate groups in said polymer.

The composition of any one of claims 35 or 36, wherein said calcium and/or magnesium cations are counterions to about 21% of the carboxylate groups in said polymer.

The composition of any one of claims 35 or 36, wherein said calcium and/or magnesium cations are counterions to about 22% of the carboxylate groups in said polymer.

40. The composition of any one of claims 35 or 36, wherein said calcium and/or magnesium cations are counterions to about 25% of the carboxylate groups in said polymer.

41. The composition of any one of claims 35 or 36, wherein said calcium and/or magnesium cations are counterions to about 29% of the carboxylate groups in said polymer.

42. The composition of claim 35, wherein said calcium and/or magnesium cations are counterions to about 5% to about 10%>, about 5% to about 15%, about 5% to about 20%, about 5% to about 25%, about 5% to about 30%, about 10% to about 15%, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 20% to about 25%o, about 20% to about 30%, or about 25% to about 30% of the carboxylate groups in said polymer.

43. The composition of claim 36, wherein said calcium and/or magnesium cations are counterions to about 15% to about 20%, about 15% to about 25%, about 15% to about 30%), about 15% to about 35%, about 20% to about 25%, about 20% to about 30%), about 20%) to about 35%, about 25% to about 30%, or about 25% to about 35%) of the carboxylate groups in said polymer.

44. The composition of any of claims 35-43, wherein said calcium and/or magnesium cations consist of calcium cations.

45. The composition of claim 44, wherein the remaining counterions to said carboxylate groups consist of hydrogen cations.

46. The composition of any of claims 35-45, wherein the counterions to said carboxylate groups consist of said calcium and/or magnesium counterions, and hydrogen counterions.

47. The composition of any of claims 35-46, wherein said calcium carbonate is present in an amount sufficient to provide from about 0.3 equivalents to about 0.6 equivalents of base per equivalent of carboxylic acid groups in said polymer.

48. The composition of any of claims 35-46, wherein said base is present in an amount from about 0.35 equivalents to about 0.5 equivalents of base per equivalent of carboxylic acid groups in said polymer.

49. The composition of any of claims 35-46, wherein said polymer comprises calcium cations that are counterions to about 20% to about 30% of the carboxylic acid groups in the polymer and the base is present in an amount sufficient to provide about 0.35 to about 0.5 equivalents of base per equivalent of carboxylic acid groups in said polymer.

50. The composition of any of claims 49, wherein said polymer comprises calcium cations that are counterions to about 25% of the carboxylic acid groups in the polymer and the base is presence in an amount sufficient to provide about 0.5 equivalents of base per equivalent of carboxylic groups in said polymer.

51. The composition of any of claims 35-50, wherein said polymer has an in vitro saline binding capacity of at least 20 times its weight.

52. The composition of any of claims 35-50, wherein said polymer has an in vitro saline binding capacity of at least 30 times its weight.

53. The composition of any of claims 35-50, wherein said polymer has an in vitro saline binding capacity of at least 40 times its weight.

54. The composition of any one of claims 35 or 36, wherein no less than about 70% of said base has a particle size of about 212 microns to about 500 microns.

55. The composition of any one of claims 35 or 36, wherein no less than about 70% of said base has a particle size of about 75 microns or less.

56. A dosage form comprising the polymer of any of claims 1-21 or the composition of any of claims 22-55.

57. A dosage form comprising:

a. the polymer of any of claims 1-21; and b. optionally an additional base.

58. The dosage form of claim 57, wherein said base is selected from an alkali metal hydroxide, an alkali metal acetate, an alkali metal carbonate, an alkali metal bicarbonate, an alkali metal oxide, an alkaline earth metal hydroxide, an alkaline earth metal acetate, an alkaline earth metal carbonate, an alkaline earth metal bicarbonate, an alkaline earth metal oxide, an organic base, choline, lysine, arginine, histidine, an acetate, a butyrate, a propionate, a lactate, a succinate, a citrate, an isocitrate, a fumarate, a malate, a malonate, an oxaloacetate, a pyruvate, a phosphate, a carbonate, a bicarbonate, a benzoate, an oxide, an oxalate, a hydroxide, an amine, a hydrogen citrate, calcium bicarbonate, calcium carbonate, calcium oxide, calcium hydroxide, magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium bicarbonate, aluminum carbonate, aluminum hydroxide, sodium bicarbonate, potassium citrate, and combinations thereof.

59. The dosage form of any of claims 56-58, further comprising one or more pharmaceutically acceptable excipient.

60. The dosage form of any of claims 56-59, wherein said dosage form is a tablet, a chewable tablet, a capsule, a suspension, an oral suspension, a powder, a gel block, a gel pack, a confection, a chocolate bar, a flavored bar, a pudding, or a sachet.

61. The dosage form of any of claims 56-59, wherein the dosage form is a sachet comprising about 1 g to about 30 g of the polymer.

62. The dosage form of any of claims 56-59, wherein the dosage form is a sachet comprising about 4 g to about 15 g of the polymer.

63. The dosage form of any of claims 56-59, wherein the dosage form is a sachet comprising about 8 g to about 15 g of the polymer

64. The dosage form of any of claims 56-59, wherein the dosage form is a sachet comprising about 8 g of the polymer.

65. The dosage form of any of claims 56-59, wherein the dosage form is a capsule comprising about 0.1 g to about 1 g of the polymer.

66. The dosage form of any of claims 56-59, wherein the dosage form is a capsule containing about 0.25 g to about 0.75 g of the polymer.

67. The dosage form of any of claims 56-59, wherein the dosage form is a capsule comprising about 0.5 g of the polymer.

68. The dosage form of any of claims 56-59, wherein the dosage form is a tablet comprising about 0.1 g to about 1.0 g of the polymer.

69. The dosage form of any of claims 56-59, wherein the dosage form is a tablet comprising about 0.3 g to about 0.8 g of the polymer.

70. The dosage form of any of claims 56-59, wherein the dosage form is a sachet, flavored bar, gel block, gel pack, pudding, or powder comprising about 1 g to about 30 g of the polymer.

71. The dosage form of any of claims 56-59, wherein the dosage form is a sachet, flavored bar, gel block, gel pack, pudding, or powder comprising about 4 g to about 20 g of the polymer.

72. The dosage form of any of claims 56-59, wherein the dosage form is a sachet, flavored bar, gel block, gel pack, pudding, or powder comprising about 4 g to about 8 g of the polymer.

73. The dosage form of any of claims 56-59, wherein the dosage form is a suspension comprising about 0.04 g of the polymer per mL of suspension to about 1 g of the polymer per mL of suspension.

74. The dosage form of any of claims 56-59, wherein the dosage form is a suspension comprising about 0.1 g of the polymer per mL of suspension to about 0.8 g of the polymer per mL of suspension.

75. The dosage form of any of claims 56-59, wherein the dosage form is a suspension comprising about 0.3 g of the polymer per mL of suspension.

76. The dosage form of any of claims 56-59, wherein the dosage form is a suspension comprising about 1 g to about 30 g of the polymer.

77. The dosage form of any of claims 73-76, wherein said suspension is an oral suspension.

78. The dosage form of any of claims 56-77, further comprising one or more additional agent.

79. The dosage form of claim 78, wherein said one or more additional agent is known to increase serum potassium.

80. The dosage form of claim 78, wherein said one or more additional agent is selected from a tertiary amine, spironolactone, fluoxetine, pyridinium and its derivatives, metoprolol, quinine, loperamide, chlorpheniramine, chlorpromazine, ephedrine, amitryptyline, imipramine, loxapine, cinnarizine, amiodarone, nortriptyline, a mineralocorticosteroid, propofol, digitalis, fluoride, succinylcholine, eplerenone, an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist, benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, candesartan, eprosartan, irbesartan, losartan, valsartan, telmisartan, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, nadolol, propranolol, sotalol, timolol, canrenone, aliskiren, aldosterone synthesis inhibitors, VAP antagonists, amiloride, triamterine, a potassium supplement, heparin, a low molecular weight heparin, a non-steroidal anti-inflammatory drug, ketoconazole, trimethoprim, pentamide, a potassium sparing diuretic, amiloride, triamterene, and combinations thereof.

81. A method of treating heart failure in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

82. A method of treating heart failure in a subject in need thereof, said method comprising:

a. identifying a subject as having heart failure; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

83. The method of claim 81 or 82 further comprising:

a. before administering said polymer or composition, determining one or more of: a baseline level of one or more ions in said subject, a baseline total body weight associated with said subject, a baseline total body water level associated with said subject, a baseline total extracellular water level associated with said subject, and a baseline total intracellular water level associated with said subject; and b. after administering said polymer or composition, determining one or more of: a second level of one or more ions in said subject, a second total body weight associated with said subject, a second total body water level associated with said subject, a second total extracellular water level associated with said subject, and a second total intracellular water level associated with said subject, wherein said second level is substantially lower than said baseline level.

84. The method of claim 83, wherein said one or more ions are selected from sodium, potassium, calcium, lithium, and magnesium.

85. The method of any of claims 82-84, wherein an acid/base status associated with said subject does not significantly change within about 1 day of administration of the polymer or composition.

86. The method of any of claims 82-85, wherein a blood pressure level associated with said subject after administration of the polymer or composition is substantially lower than a baseline blood pressure level associated with said subject before administration of the polymer or composition.

87. The method of claim 86, wherein said blood pressure level is one or more of: a systolic blood pressure level, a diastolic blood pressure level, and a mean arterial pressure level.

88. The method of any of claims 82-87, wherein a symptom of fluid overload associated with said subject, determined after administration of the polymer or composition, is reduced compared to a baseline level determined before administration of the composition.

89. The method of claim 88, wherein said symptom is one or more of: difficulty breathing when lying down, difficulty breathing with normal physical activity, ascites, fatigue, shortness of breath, increased body weight, peripheral edema, and pulmonary edema.

90. The method of any of claims 82-89, wherein said subject is on concomitant diuretic therapy.

91. The method of claim 90, wherein said diuretic therapy is reduced or discontinued after administration of the composition.

92. The method of any of claims 82-91, further comprising co-administering to said subject an agent known to increase serum potassium levels.

93. The method of claim 92, wherein said agent is one or more of: a tertiary amine, spironolactone, fluoxetine, pyridinium and its derivatives, metoprolol, quinine, loperamide, chlorpheniramine, chlorpromazine, ephedrine, amitryptyline, imipramine, loxapine, cinnarizine, amiodarone, nortriptyline, a mineralocorticosteroid, propofol, digitalis, fluoride, succinylcholine, eplerenone, an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist, benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, candesartan, eprosartan, irbesartan, losartan, valsartan, telmisartan, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, nadolol, propranolol, sotalol, timolol, canrenone, aliskiren, aldosterone synthesis inhibitors, VAP antagonists, amiloride, triamterine, a potassium supplement, heparin, a low molecular weight heparin, a non-steroidal anti-inflammatory drug, ketoconazole, trimethoprim, pentamide, a potassium sparing diuretic, amiloride, triamterene, and combinations thereof.

94. The method of claim 92, wherein a dose of said agent is increased after administration of the polymer or composition.

95. The method of any of claims 82-94, wherein said subject is co-administered a blood pressure medication.

96. The method of claim 95, wherein a dose of said blood pressure medication is reduced after administration of the polymer or composition.

97. A method of treating end stage renal disease in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

98. A method of treating end stage renal disease in a subject in need thereof, said method comprising:

a. identifying end stage renal disease in said subject or identifying a risk that the subject will develop end stage renal disease; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

99. The method of claim 97 or 98, wherein the subject is on dialysis.

100. The method of any of claims 97-99, wherein said subject also has heart failure.

101. The method of claim 99 wherein interdialytic weight gain in a subject on dialysis is reduced after administration of the polymer or composition.

102. The method of claim 99 or 101, wherein one or more symptom of intradialytic hypotension are reduced after administration of the polymer or composition.

103. The method of claim 102, where said one or more symptom is selected from vomiting, fainting, an abrupt decrease in blood pressure, seizures, dizziness, severe abdominal cramping, severe leg or arm muscular cramping, intermittent blindness, infusion, medication, dialysis session interruption, and dialysis session discontinuation.

104. The method of claim any of claims 97-103, further comprising:

a. before administering the polymer or composition, determining a baseline level of one or more ions in said subject; and b. after administering the polymer or composition, determining a second level of said one or more ions in said subject, wherein said second level of one or more ions is substantially less than said baseline level of one or more ions.

105. The method of claim 104, wherein said one or more ions are selected from sodium, potassium, calcium, lithium, magnesium, and ammonium.

106. The method of claim any of claims 97-105, wherein an acid/base status associated with said subject does not significantly change within about 1 day of administration of the polymer or composition.

107. The method of claim any of claims 99, 101, or 102, further comprising:

a. determining a baseline predialytic-to-postdialytic blood pressure drop associated with said subject before administration of the polymer or composition; and b. determining a second predialytic-to-postdialytic blood pressure drop associated with said subject after administration of the polymer or composition, wherein said second blood pressure drop is smaller than said baseline blood pressure drop.

108. A method of treating chronic kidney disease in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

109. A method of treating chronic kidney disease in a subject in need thereof, said method comprising:

a. identifying the subject as having a chronic kidney disease; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

110. The method of claim 108 or 109, wherein a symptom of fluid overload is reduced after administration of the polymer or composition.

111. The method of claim 110, wherein said symptom is one or more of: difficulty breathing at rest, difficulty breathing during normal physical activity, edema, pulmonary edema, hypertension, peripheral edema, leg edema, ascites, and/or increased body weight.

112. The method of claim any of claims 108-111, wherein a blood pressure level associated with said subject after administration of the polymer or composition is substantially lower than a baseline blood pressure level associated with said subject before administration of the composition.

113. The method of claim 112, wherein said blood pressure level is one or more of: a systolic blood pressure level, a diastolic blood pressure level, and a mean arterial pressure level.

114. The method of any of claims 108-113, wherein a co-morbidity of chronic kidney disease is reduced or alleviated after administration of the composition.

115. The method of claim 114, wherein said co-morbidity is one or more of: fluid overload, edema, pulmonary edema, hypertension, hyperkalemia, excess total body sodium, and uremia.

116. The method of any of claims 108-115, further comprising:

a. before administering the polymer or composition, determining one or more of: a baseline level of one or more ions in said subject, a baseline total body weight associated with said subject, a baseline total body water level associated with said subject, a baseline total extracellular water level associated with said subject, and a baseline total intracellular water level associated with said subject; and b. after administering the polymer or composition, determining one or more of: a second level of said one or more ions in said subject, a second total body weight associated with said subject, a second total body water level associated with said subject, a second total extracellular water level associated with said subject, and a second total intracellular water level associated with said subject wherein said second level is substantially less than said baseline level.

117. The method of claim 116, wherein said one or more ions are selected from sodium, potassium, calcium, lithium, magnesium, and ammonium.

118. The method of any of claims 108-117, wherein an acid/base status associated with said subject does not significantly change within about 1 day of administration of the polymer or composition.

119. A method of treating hypertension in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

120. A method of treating hypertension in a subject in need thereof, said method comprising:

a. identifying the subject as having, or as having a risk of developing, hypertension; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

121. The method of claim 119 or 120, wherein a blood pressure level associated with said subject after administration of the polymer or composition is substantially lower than a baseline blood pressure level associated with said subject before administration of the composition.

122. The method of claim 121, wherein said blood pressure level is one or more of: a systolic blood pressure level, a diastolic blood pressure level, and a mean arterial pressure level.

123. The method of claim any of claims 1 19-122, wherein a symptom of fluid overload associated with said subject, determined after administration of the polymer or composition, is reduced compared to a baseline level determined before administration of the polymer or composition.

124. The method of claim 123, wherein the symptom is one or more of: difficulty breathing when lying down, ascites, fatigue, shortness of breath, increased body weight, peripheral edema, and pulmonary edema.

125. The method of any of claims 119-124, wherein said subject is on concomitant diuretic therapy.

126. The method of claim 125, wherein said diuretic therapy is reduced or discontinued after administration of the polymer or composition.

127. The method of any of claims 119-126, wherein said subject has one or more of: salt sensitive hypertension and refractory hypertension.

128. A method of treating hyperkalemia in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

129. A method of treating hyperkalemia in a subject in need thereof, said method comprising:

a. identifying the subject as having, or as having a risk of developing, hyperkalemia; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

130. The method of claim 128 or 129, further comprising, after administering said polymer or composition, determining a potassium level in said subject, wherein said potassium level is within a normal potassium level range for said subject.

131. The method of any of claims 128-130, further comprising co-administering to said subject one or more of: mannitol, sorbitol, calcium acetate, sevelamer carbonate, sevelamer hydrochloride, a tertiary amine, spironolactone, fluoxetine, pyridinium and its derivatives, metoprolol, quinine, loperamide, chlorpheniramine, chlorpromazine, ephedrine, amitryptyline, imipramine, loxapine, cinnarizine, amiodarone, nortriptyline, a mineralocorticosteroid, propofol, digitalis, fluoride, succinylcholine, eplerenone, an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist, benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, candesartan, eprosartan, irbesartan, losartan, valsartan, telmisartan, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, nadolol, propranolol, sotalol, timolol, canrenone, aliskiren, aldosterone synthesis inhibitors, VAP antagonists, amiloride, triamterine, a potassium supplement, heparin, a low molecular weight heparin, a non-steroidal anti-inflammatory drug, ketoconazole, trimethoprim, pentamide, a potassium sparing diuretic, amiloride, triamterene, and combinations thereof.

132. The method of any of claims 128-131, further comprising:

a. before administering the polymer or composition, determining a baseline level of potassium in said subject; and b. after administering the polymer or composition, determining a second level of potassium in said subject, wherein said second level of potassium is substantially less than said baseline level of potassium.

133. The method of any of claims 128-132, wherein an acid/base status associated with said subject does not significantly change within about 1 day of administration of the polymer or composition.

134. A method of treating a high sodium level in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

135. A method of treating a high sodium level in a subject in need thereof, said method comprising:

a. identifying an elevated sodium level associated with said subject; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

136. The method of claim 134 or 135, wherein the high sodium level is not caused by dehydration.

137. The method of any of claims claim 134-136, further comprising co-administering to said subject an agent known to cause sodium retention.

138. The method of claim 137, wherein said agent is one or more of: estrogen containing compositions, mineralocorticoids, loop diuretics, thiazide diuretics, osmotic diuretics, lactulose, cathartics, phenytoin, lithium, Amphotericin B, demeclocycline, dopamine, ofloxacin, orlistat, ifosfamide, cyclophosphamide, hyperosmolar radiographic contrast agents, cidofovir, ethanol, foscarnet, indinavir, libenzapril, mesalazine, methoxyflurane, pimozide, rifampin, streptozotocin, tenofir, triamterene, cholchicine, and sodium supplements.

139. The method of any of claims 134-138, further comprising:

a. before administering the polymer or composition, determining a baseline total body sodium; and b. after administering the polymer or composition, determining a second total body sodium in said subject, wherein said second total body sodium is substantially less than said baseline total body sodium.

140. A method of treating a fluid overload state in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

141. A method of treating a fluid overload state in a subject in need thereof, said method comprising:

a. identifying a fluid overload state or a risk of developing a fluid overload state in said subject; and

b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

142. The method of claim 149 or 141, wherein said fluid overload state or said risk of developing a fluid overload state is determined by assessing one or more of: difficulty breathing when lying down, ascites, fatigue, shortness of breath, increased body weight, peripheral edema, and pulmonary edema associated with said subject.

143. The method of any of claims 140-142, wherein said subject is on concomitant diuretic therapy.

The method of claim 143, wherein said diuretic therapy is reduced or discontinued after administration of the polymer or composition.

145. The method of any of claims 140-144, further comprising:

a. before administering the polymer or composition, determining one or more of: a baseline level of one or more ions in said subject, a baseline total body weight associated with said subject, a baseline total body water level associated with said subject, a baseline total extracellular water level associated with said subject, and a baseline total intracellular water level associated with said subject; and

b. after administering the polymer or composition, determining one or more of: a second level of said one or more ions in said subject, a second total body weight associated with said subject, a second total body water level associated with said subject, a second total extracellular water level associated with said subject, and a second total intracellular water level associated with said subject,

wherein said second level is substantially less than said baseline level.

146. The method of claim 145, wherein said one or more ions are selected from sodium, potassium, calcium, lithium, and magnesium.

147. The method of claim any of claims 140-146, wherein an acid/base status associated with said subject does not significantly change within about 1 day of administration of the polymer or composition.

148. A method of treating a fluid maldistribution state in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

149. A method of treating a fluid maldistribution state in a subject in need thereof, said method comprising:

a. identifying a fluid maldistribution state or a risk of developing a fluid maldistribution state in said subject; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

150. A method of treating edema in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1- 21, the composition of any of claims 22-55, or the dosage form of any of claims 56- 80.

151. A method of treating edema in a subject in need thereof, said method comprising: a. determining an edematous state or a risk of developing an edematous state in said subject; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

152. The method of claim 150 or 151 further comprising:

a. before administering said polymer or composition, determining one or more of: a baseline level of one or more ions in said subject, a baseline total body weight associated with said subject, a baseline total body water level associated with said subject, a baseline total extracellular water level associated with said subject, and a baseline total intracellular water level associated with said subject; and b. after administering said polymer or composition, determining one or more of: a second level of one or more ions in said subject, a second total body weight associated with said subject, a second total body water level associated with said subject, a second total extracellular water level associated with said subject, and a second total intracellular water level associated with said subject wherein said second level is substantially lower than said baseline level.

153. The method of claim 152, wherein said one or more ions are selected from sodium, potassium, calcium, lithium, and magnesium.

154. The method of any of claims 150-152, wherein an acid/base status associated with said subject does not significantly change within about 1 day of administration of the polymer or composition.

155. The method of any of claims 150-154, wherein a blood pressure level associated with said subject after administration of the polymer or composition is substantially lower than a baseline blood pressure level associated with said subject before administration of the composition.

156. The method of claim 155, wherein said blood pressure level is one or more of: a systolic blood pressure level, a diastolic blood pressure level, and a mean arterial pressure level.

157. The method of any of claims 150-156, wherein a symptom of edema associated with said subject, determined after administration of the polymer or composition, is reduced compared to a baseline level determined before administration of the polymer or composition.

158. The method of claim 157, wherein said symptom is one or more of: difficulty breathing when lying down, shortness of breath, peripheral edema, and leg edema.

159. The method of any of claims 150-158, wherein said subject is on concomitant diuretic therapy.

160. The method of claim 159, wherein said diuretic therapy is reduced or discontinued after administration of the polymer or composition.

161. A method of treating ascites in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1- 21, the composition of any of claims 22-55, or the dosage form of any of claims 56- 80.

162. A method of treating ascites in a subject in need thereof, said method comprising: a. determining an ascitic state or a risk of developing an ascitic state in said subject; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

163. The method of claim 161 or 162, further comprising:

a. before administering the polymer or composition, determining a baseline potassium level associated with said subject; and b. after administering the polymer or composition, determining a second potassium level associated with said subject, wherein said second potassium level is substantially less than said baseline potassium level.

164. The method of any of claims 161-163, further comprising co-administering to said subject an agent known to increase serum potassium levels.

165. The method of claim 164, wherein said agent is one or more of: a tertiary amine, spironolactone, fluoxetine, pyridinium and its derivatives, metoprolol, quinine, loperamide, chlorpheniramine, chlorpromazine, ephedrine, amitryptyline, imipramine, loxapine, cinnarizine, amiodarone, nortriptyline, a mineralocorticosteroid, propofol, digitalis, fluoride, succinylcholine, eplerenone, an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist, benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, candesartan, eprosartan, irbesartan, losartan, valsartan, telmisartan, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, nadolol, propranolol, sotalol, timolol, canrenone, aliskiren, aldosterone synthesis inhibitors, VAP antagonists, amiloride, triamterine, a potassium supplement, heparin, a low molecular weight heparin, a non-steroidal anti-inflammatory drug, ketoconazole, trimethoprim, pentamide, a potassium sparing diuretic, amiloride, triamterene, and combinations thereof.

166. The method of any of claims 161-165, further comprising administering to said subject a diuretic.

167. The method of claim 166, further comprising reducing or discontinuing the administration of said diuretic after administration of the polymer or composition.

168. A method of treating nephrotic syndrome in a subject in need thereof, said method comprising administering to said subject the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

169. A method of treating nephrotic syndrome in a subject in need thereof, said method comprising:

a. identifying the subject as having nephrotic syndrome or a risk of developing nephrotic syndrome; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

170. The method of claim 169 or 170, further comprising:

171. The method of claim 170, wherein said one or more ions are selected from sodium, potassium, calcium, lithium, and magnesium.

172. The method of any of claims 169-171, wherein an acid/base status associated with said subject does not significantly change within about 1 day of administration of the polymer or composition.

173. The method of any of claims 169-172, wherein a blood pressure level associated with said subject after administration of the polymer or composition is substantially lower than a baseline blood pressure level associated with said subject before administration of the polymer or composition.

174. The method of claim 173, wherein said blood pressure level is one or more of: a systolic blood pressure level, a diastolic blood pressure level, and a mean arterial pressure level.

175. The method of claim any of claims 169-174, wherein a symptom of fluid overload associated with said subject, determined after administration of the polymer or composition, is reduced compared to a baseline level determined before administration of the polymer or composition.

176. The method of claim 175, wherein said symptom is one or more of: difficulty breathing when lying down, shortness of breath, peripheral edema, and leg edema.

177. The method of any of claims 169-176, wherein said subject is on concomitant diuretic therapy.

178. The method of claim 177, wherein said diuretic therapy is reduced or discontinued after administration of the polymer or composition.

179. A method of treating interdialytic weight gain in a subject in need thereof, said method comprising administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

180. A method of treating interdialytic weight gain in a subject in need thereof, said method comprising:

a. identifying interdialytic weight gain or an elevated risk of developing interdialytic weight gain associated with said subject; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

181. The method of claim 180, wherein said elevated risk is identified by any combination of: subject medical history, frequent episodes of blood pressure drops during dialysis, documentation of elevated IDWG between dialysis sessions, diagnosis of one or more symptoms of interdialytic weight gain in said subject, or identification of a treatment regimen for said subject that is commonly accompanied by an elevated risk of developing interdialytic weight gain.

182. A method of treating a disease or disorder in a subject in need thereof, said method comprising administering to said subject the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

183. A method of treating a disease or disorder in a subject in need thereof, said method comprising:

a. identifying a disease or a disorder in said subject, or identifying a risk that said subject will develop a disease or disorder; and b. administering to said subject an effective amount of the polymer of any of claims 1-21, the composition of any of claims 22-55, or the dosage form of any of claims 56-80.

184. The method of claim 182 or 183, wherein said disease or disorder is one or more of: heart failure, a renal insufficiency disease, end stage renal disease, liver cirrhosis, chronic renal insufficiency, chronic kidney disease, fluid overload, fluid maldistribution, edema, pulmonary edema, peripheral edema, lymphedema, nephrotic edema, idiopathic edema, ascites, cirrhotic ascites, interdialytic weight gain, high blood pressure, hyperkalemia, hypernatremia, abnormally high total body sodium, hypercalcemia, tumor lysis syndrome, head trauma, an adrenal disease, hyporeninemic hypoaldosteronism, hypertension, salt-sensitive hypertension, refractory hypertension, renal tubular disease, rhabdomyolysis, crush injuries, renal failure, acute tubular necrosis, insulin insufficiency, hyperkalemic periodic paralysis, hemolysis, malignant hyperthermia, pulmonary edema secondary to cardiogenic pathophysiology, pulmonary edema with non-cardiogenic origin, drowning, acute glomerulonephritis, allergic pulmonary edema, high altitude sickness, Adult Respiratory Distress Syndrome, traumatic edema, cardiogenic edema, acute hemorrhagic edema, heatstroke edema, facial edema, eyelid edema, angioedema, cerebral edema, scleral edema, nephritis, nephrosis, nephrotic syndrome, glomerulonephritis, and/or renal vein thrombosis.

185. The method of any of claims 81-184, wherein said polymer or composition is administered from 1 time every 3 days to about 4 times per day.

186. The method of any of claims 81-184, wherein said polymer or composition is administered from 1 to 4 times per day.

187. The method of any of claims 81-184, wherein said polymer or composition is administered from 1 to 2 times per day.