WO2008011126A2 - Liquid compositions of calcium acetate - Google Patents
Liquid compositions of calcium acetate Download PDFInfo
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- WO2008011126A2 WO2008011126A2 PCT/US2007/016415 US2007016415W WO2008011126A2 WO 2008011126 A2 WO2008011126 A2 WO 2008011126A2 US 2007016415 W US2007016415 W US 2007016415W WO 2008011126 A2 WO2008011126 A2 WO 2008011126A2
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- calcium acetate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/04—Chelating agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
Definitions
- Phosphorous binders bind phosphorus in the form of a phosphorous ion within the stomach and intestines. This process is thought to result from a chemical reaction between dietary phosphorus and the cation present in the binder compound. The reaction causes the formation of insoluble and hence unabsorbable phosphate compounds. The cation in some phosphorous binders is aluminum or calcium. Despite their capacity for binding phosphorus, large quantities of antacids must be ingested over a long period of time for them to be effective. Therefore, dosage size and palatability are particularly important for patients with chronic renal disease. [0004] Prescription medications typically effective in managing or preventing hyperphosphatemia include calcium acetate.
- Calcium acetate treatment is one of the most effective methods for management of chronic renal disease. When administered orally, calcium acetate is more effective than any other calcium-containing binder in binding phosphorus. Used alone or in combination with other materials, calcium acetate binds phosphorus in the gastrointestinal tract and reduces the percentage of consumed phosphorus (i.e., of a given "dose" of phosphorus) which is absorbed into the bloodstream. This compound is most effective in reducing phosphorous absorption when it is administered close in time to food consumption. Despite these benefits, calcium acetate treatments heretofore known in the art have not been without their drawbacks.
- Calcium acetate is a solid, and to date, it is formulated in various solid dosage forms, such as pills and tablets. See, e.g., U.S. Patent Nos. 6,875,445, 4,870,105, and 6,576,665.
- dosage forms of calcium acetate present a twofold clinical dilemma, particularly for dialysis patients, who are a significant patient population that is treated with calcium acetate.
- dialysis patients who may suffer from renal diseases such as end stage renal disease, find such solid dosage forms difficult to swallow due to their bulk size. The difficulty is exacerbated because such patients need to consume large dosages of calcium acetate, and consequently they must swallow many pills. Additionally, as mentioned above, such patients need to consume the pills prior to a meal.
- a third and equally undesirable characteristic of calcium acetate is that it has a repugnant bitter taste that is very unpleasant to the palate and is difficult to mask. Because solid dosage forms of calcium acetate must be able to disintegrate in the intestine, oral consumption of calcium acetate pills formulated to achieve this objective often leave particles of calcium acetate in patients' mouths, which particles leave the characteristic bad taste. [0006] On the other hand, calcium acetate is water soluble, and liquid formulations of calcium acetate might be thought to alleviate the above-mentioned shortcomings of solid dosage forms of the drug. However, solutions of calcium acetate are many times more potently repugnant to the palate than are solid dosage forms.
- a liquid pharmaceutical composition comprising an aqueous solution of at least calcium acetate, at least one polyol, at least one sweetener, and at least one taste masking agent.
- the liquid composition comprises about 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 21% calcium acetate (w/v).
- the liquid composition comprises about 13-15%, 12-16%, or 11-17% calcium acetate (w/v); and in other embodiments the liquid composition comprises about 14% or 14.3% calcium acetate (w/v).
- the liquid composition comprises about 2%, 3%, 4%, 5%, or 6% calcium acetate (w/v).
- five milliliters (mL) of the inventive composition provides about 710 milligrams of hydrous calcium acetate; in another embodiment, five milliliters of the inventive composition provides about 667 milligrams of anhydrous calcium acetate.
- the inventive composition provides about 5-200 milliequivalents of calcium per five milliliters of composition.
- the inventive composition provides about 169 milligrams of calcium per five milliliters.
- the inventive composition provides about 8 or about 8.45 milliequivalents of calcium per five milliliters.
- the liquid composition comprises about 20% (w/v) to about 50% (w/v) of polyol (also known as sugar alcohol), or about 15% (w/v) to about 50% (w/v) of polyol.
- polyol also known as sugar alcohol
- Exemplary polyols that can be used in the inventive compositions include sorbitol, xylitol, maltitol, glycerine, propylene glycol, erythritol and combinations thereof.
- the liquid composition comprises about 15% (w/v) to about 40% (w/v) sorbitol or 15% (w/v) to about 25% (w/v) sorbitol, or about 16% (w/v) to about 26% (w/v) sorbitol or about 18% (w/v) to about 24% (w/v) sorbitol and in other embodiments, the liquid composition comprises about 21% (w/v) sorbitol. In other embodiments the liquid composition comprises about 15% (w/v) to about 40% (w/v) of a combination of sorbitol and maltitol.
- the liquid composition comprises about 15% (w/v) to 25% (w/v) of maltitol and in other embodiments, the composition comprises about 20% (w/v) maltitol. In other embodiments the liquid composition comprises about 1% (w/v) to about 25% (w/v) of glycerine, and in other embodiments the liquid composition comprises about 5% (w/v) glycerine. In other embodiments the liquid composition comprises about 1.5% to about 2.5% propylene glycol (w/v).
- the sweetener of the liquid composition is an artificial sweetener (also known in the art as a "high intensity sweetener").
- artificial sweeteners include sucralose, acesulfame potassium, aspartame, and the saccharins, hi other embodiments, the artificial sweetener is selected from sucralose and saccharin.
- the sucralose is present at a concentration of about 0.35% (w/v); in other embodiments, the concentration of sucralose is from about 0.1% (w/v) to about 0.8% (w/v).
- the concentration of saccharin is about 0.05% (w/v) to about 0.25% (w/v) or 0.2% (w/v) to about 0.8% (w/v) and in other embodiments, the concentration of saccharin is about 0.15% (w/v).
- a suitable taste masking agent for use in the inventive composition is monoammonium glycyrrhizinate (Magnasweet).
- monoammonium glycyrrhizinate is present in the composition at about 0.05% (w/v) to about 0.3% (w/v) and in other embodiments, monoammonium glycyrrhizinate is present in the composition at about 0.2% (w/v) to about 0.8% (w/v). In other embodiments the monoammonium glycyrrhizinate is present in the composition at about 0.25 % (w/v).
- the inventive composition may also contain a flavoring agent; suitable flavoring agents include berry flavor, root beer flavor, cream flavor, chocolate flavor, peppermint flavor, spearmint flavor and wintergreen flavor and combinations thereof. Suitable berry flavoring agents include black cherry, strawberry, cherry, blueberry, raspberry and the like. So-called “artificial” and “natural” flavoring agents are included.
- the inventive composition may also comprise menthol flavor.
- the inventive composition may also contain one or more preservatives; exemplary preservatives include methylparaben, propylparaben, sorbic acid, sodium benzoate, potassium sorbate and combinations thereof.
- the inventive composition may also contain povidone.
- the composition comprises about 0.5% (w/v) to 1.0% (w/v) povidone, and in other embodiments, the composition comprises 0.75% (w/v) povidone. In other embodiments, the composition comprises less than about 5% (w/v), or less than about 4% (w/v), or less than about 3% (w/v), or less than about 2% (w/v), or less than about 1% (w/v) povidone.
- An exemplary povidone that can be used in the inventive compositions is Povidone 25.
- the above-described calcium acetate compositions do not contain one or more of the following ingredients: magnesium salt, calcium- peptide compounds (for example, so-called CPP-calcium), or polyvinylpyrrolidone (also known as “PVP” and “Povidone”).
- the inventive aqueous composition comprises about 7- 21% (w/v) calcium acetate, sorbitol, glycerine, monoammonium glycyrrhizinate, and sucralose.
- a composition may further comprise black cherry flavor and menthol flavor.
- a composition may further comprise propylene glycol, methylparaben, and propylparaben.
- the inventive aqueous composition comprises about 14.3% (w/v) calcium acetate, about 21% (w/v) sorbitol, about 5% (w/v) glycerine, about 0.25% (w/v) monoammonium glycyrrhizinate, and about 0.35% (w/v) sucralose.
- a composition may further comprise black cherry flavor and menthol flavor (exemplary amount for each flavoring agent is 0.2% (w/v)).
- Such a composition may further comprise propylene glycol (exemplary concentration is 2% (w/v)), methylparaben (exemplary concentration 0.05% (w/v)) and propylparaben (exemplary concentration 0.005% (w/v)).
- the amounts of black cherry and menthol flavor are provided q.s. as needed.
- the inventive aqueous composition comprises about 7-21% (w/v) calcium acetate, sorbitol, glycerine, monoammonium glycyrrhizinate, and sucralose.
- a composition may further comprise black cherry flavor and menthol flavor.
- a composition may further comprise propylene glycol, povidone, and methylparaben.
- the inventive aqueous composition comprises about 14.3% (w/v) calcium acetate, about 21% (w/v) sorbitol, about 5% (w/v) glycerine, about 0.25% (w/v) monoammonium glycyrrhizinate, and about 0.35% (w/v) sucralose.
- a composition may further comprise black cherry flavor and menthol flavor (exemplary amount for each flavoring agent is 0.2% (w/v)).
- Such a composition may further comprise propylene glycol (exemplary concentration is 2% (w/v)), methylparaben (exemplary concentration 0.2% (w/v)) and povidone (exemplary concentration 0.75% (w/v)).
- the amounts of black cherry and menthol flavor are provided q.s. as needed.
- the inventive aqueous composition comprises about 7-21% (w/v) calcium acetate, maltitol, glycerine, monoammonium glycyrrhizinate, and sucralose.
- a composition may further comprise black cherry flavor and menthol flavor.
- a composition may further comprise propylene glycol, povidone, and methylparaben.
- the inventive aqueous composition comprises about 14.3% (w/v) calcium acetate, about 20% (w/v) maltitol, about 5% (w/v) glycerine, about 0.25% (w/v) monoammonium glycyrrhizinate, and about 0.35% sucralose.
- a composition may further comprise black cherry flavor and menthol flavor (exemplary amount for each flavoring agent is 0.2% (w/v)).
- Such a composition may further comprise propylene glycol (exemplary concentration is 2% (w/v)), methylparaben (exemplary concentration 0.2% (w/v)) and povidone (exemplary concentration 0.75% (w/v)).
- the amounts of black cherry and menthol flavor are provided q.s. as needed.
- the invention also provides, in another embodiment, a method for binding phosphorus within the gastrointestinal tract of an individual, comprising administering to the individual an aqueous calcium acetate solution, as described above.
- the present invention will be useful in treating individuals in need of dialysis and/or suffering from one or more of the following disorders: renal disease, kidney disease, end stage renal disease, and chronic kidney disease.
- the present invention stems from the surprising discovery that calcium acetate can be formulated in a very low volume solution while simultaneously being effectively taste-masked.
- the liquid composition of calcium acetate according to the invention thus possesses a number of advantages over solid formulations of calcium acetate, and overcomes limitations that would otherwise be encountered in attempts to administer calcium acetate in liquid form.
- the liquid composition obviates the need for patients to consume large numbers of pills by eliminating any calcium acetate pills.
- patients taking other medications can swallow pills with the liquid composition of this invention.
- composition of this invention can be formulated in very small volumes, and it therefore contributes only a negligible amount of fluid to dialysis patients' daily fluid intake.
- the inventive composition can be ingested orally just before meals.
- the patients can swallow the inventive composition at intervals throughout their meals, or just before and just after meals. Not having to swallow multiple pills makes the overall treatment regimen a more pleasant experience, thereby ensuring high levels of patient compliance.
- the inventive composition is palatable, i.e., has a good taste, and the taste of the calcium acetate is masked, which contributes to high levels of patient compliance.
- the inventive composition can be formulated to have a low calorie content and/or a low glycemic index compared with liquid pharmaceutical formulations that are made using traditional sweeteners such as glucose and fructose.
- the inventive compositions are therefore suitable for administration to patients with diabetes. It is known in the art that sugars have a calorie content of about 4 calories per gram.
- the sweetener can comprise a so-called artificial sweetener (sucralose, saccharin, etc.), which imparts no or negligible calories.
- the polyol component of the inventive compositions also imparts some sweetness, but it is known in the art that polyols (sugar alcohols) contribute fewer calories per gram than simple sugars and also have a lower glycemic index than simple sugars. For example, sorbitol has about 2.6 calories per gram and maltitol has about 3 calories per gram.
- the inventive compositions of the invention have no more than about 1 calorie per milliliter and in other embodiments the inventive compositions have no more than about 0.8 calories per milliliter.
- an advantage of the liquid composition is that calcium acetate can be formulated in very low volume solutions.
- typical calcium acetate concentrations range from about 7% (w/v) to about 21% (w/v), based on the total volume of the composition. In some embodiments, the concentration is from about 12% (w/v) to about 16% (w/v), and in other embodiments the concentration is about 14% or about 14.3% (w/v).
- the calcium acetate in the inventive composition is in aqueous solution. In still other embodiments, the calcium acetate concentration of the inventive composition is about 6% or 5% or 4% or 3% or 2% (w/v).
- the liquid compositions typically supply an average dose of calcium acetate in about 10 mL or less.
- the volume can range from about 4 mL to about 7 mL.
- Illustrative of the volume of a dose is a composition measuring about 5 mL, which delivers the equivalent of one (1) tablet of a solid calcium acetate formulation, i.e., pill.
- Such a 5 mL dose can supply about 710 milligrams of hydrous calcium acetate, or about 667 milligrams of anhydrous calcium acetate.
- a tablespoon of the present composition i.e., ⁇ 15 mL
- 5 mL supplies about 1.065 grams of hydrous calcium acetate or about 1.0 gram of anhydrous calcium acetate.
- the composition of the invention comprises a taste masking agent.
- Some taste masking agents known in the art are characterized additionally as sweeteners. Regardless of whether a particular compound is recognized for imparting sweetness, it should at least possess the property of being able to mask tastes in the mouth.
- An exemplary taste masking agent in this regard is monoammonium glycyrrhizinate (Magnasweet).
- the inventive composition also comprises a sweetener.
- Various sweeteners are contemplated, including but not limited to simple sugars such as sucrose, dextrose, fructose, maltose, and the like.
- the inventive composition is "low calorie” or “light”, “sugar-free”, or “calorie-free.”
- the sweetener in the inventive compositions may be a so-called “artificial sweetener” (also known as “high-intensity sweetener”), such as sucralose, acesulfame potassium, saccharin, and aspartame, or any combination thereof.
- artificial sweeteners is desirable for adding sweetness without the addition of calories.
- the polyol in the inventive composition may also provide some sweetening and the lower calorie content of polyols, and lower glycemic index (compared to simple sugars) make the inventive compositions suitable for low calorie diets. Additionally, the inventive compositions that are low calorie and/or low glycemic index would be suitable for diabetic patients.
- sucgar-free means that a product contains no amount of, or only trivial or “physiologically inconsequential" amounts of sugars.
- sucgar free means less than 0.5 g of sugars per serving.
- Calorie free means fewer than 5 calories per serving. Examples of synonyms for "free” include “without,” “no” and “zero.” Those products sweetened only with artificial sweeteners and/or sugar alcohols (and containing no other sugars) can be classified as “sugar- free.”
- low calorie is understood to mean 40 calories or less per reference amount.
- the composition comprises the sweetener sucralose and the polyol sorbitol, and the taste masking agent monoammonium glycyrrhizinate.
- the composition comprises the sweetener sucralose and the polyols sorbitol and maltitol, and the taste masking agent monoammonium glycyrrhizinate.
- the composition comprises the sweetener sucralose and the polyol maltitol, and the taste masking agent monoammonium glycyrrhizinate.
- composition of the invention contemplates various concentrations of calcium acetate, a taste masking agent, and a sweetener to achieve a palatable composition.
- the taste masking agent is present in a concentration of about 0.05% (w/v) to about 0.8% (w/v) based on the total volume of the composition.
- concentrations are about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75% and 0.8% (w/v).
- the taste masking agent is present in a concentration of about 0.2 % (w/v) to about 0.8% (w/v) based on the total volume of the composition.
- Exemplary concentrations are about 0.25%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7% and 0.8% (w/v).
- a preferred composition prescribed by the foregoing considerations, and for use in the methods described herein, comprises calcium acetate in a concentration about 14% (w/v), maltitol in a concentration of about 20% (w/v), sucralose in a concentration of about 0.35% (w/v), and monoammonium glycyrrhizinate in a concentration of about 0.25% (w/v), based upon the total volume of the composition.
- a preferred composition prescribed by the foregoing considerations, and for use in the methods described herein, comprises calcium acetate in a concentration of about 14% (w/v), sorbitol in a concentration of about 21% (w/v), sucralose in a concentration of about 0.35% (w/v), and monoammonium glycyrrhizinate in a concentration of about 0.25% (w/v), based upon the total volume of the composition.
- the inventive composition may also contain a flavoring agent; suitable flavoring agents include berry flavor, root beer flavor, cream flavor, chocolate flavor, peppermint flavor, spearmint flavor and wintergreen flavor and combinations thereof. Suitable berry flavoring agents include black cherry, strawberry, cherry, blueberry, raspberry and the like.
- the inventive composition may also comprise menthol flavor.
- the amounts of the flavoring agents used will vary depending on taste preferences and the other ingredients in the composition, but will be a very small percentage of the overall composition; for example, in Examples 1-4, the artificial black cherry flavor and menthol are each present at a concentration of 0.2% (w/v).
- the flavoring agents will typically make up no more than 1% (w/v) of the calcium acetate composition.
- buffers such as citric acid or its corresponding salts
- surfactants such as methylcellulose, carboxymethylcellulose, polyvinylpyrrolidone, and the like
- preservatives such as methyl and propyl parabens, and the like
- anti-oxidants such as benzoate salts, and the like
- chelating agents such as EDTA and its salts and the like.
- the amount and type of preservative present in the liquid composition of the invention can be determined as known by those of skill in the art.
- methylparaben can be used in a concentration of from 0.01% (w/v) to about 0.2% (w/v), or from about 0.1% (w/v) to about 0.3% (w/v) and propylparaben can be used in a concentration of from about 0.001% (w/v) to about 0.05% (w/v).
- Povidone can be used in a concentration of about 0.5% (w/v) to about 1.0% (w/v).
- the concentration of methylparaben is about 0.2% (w/v) and the concentration of povidone is about 0.75% (w/v).
- the composition of methylparaben is about 0.05% (w/v) and the concentration of propylparaben is about 0.005% (w/v); in another embodiment, the composition of methylparaben is about 0.01% (w/v) and the concentration of propylparaben is about 0.025% (w/v).
- inventive compositions also include liquid calcium acetate compositions that do not contain one or more of the following ingredients: magnesium salt, calcium-peptide compounds (for example, so-called CPP-calcium), or polyvinylpyrrolidone (PVP).
- magnesium salt for example, so-called CPP-calcium
- PVP polyvinylpyrrolidone
- the inventive composition can be formulated to have a final pH of about 6.0 to about 7.0.
- the pH can be about 6.0 to about 7.2.
- the pH of the inventive composition is about 6.8.
- Any of the embodiments of the liquid composition herein described are suitable for use in the inventive method for binding phosphorus within the gastrointestinal tract of an individual.
- the method comprises administering to the individual an aqueous solution of at least calcium acetate as described herein.
- the administration in one embodiment, is via oral ingestion of the composition.
- the use of calcium acetate to treat hyperphosphatemia is well known in the art, and hence the dosages required to treat this condition can also be readily determined depending on patient condition, history and need.
- the typical dose of calcium supplied by calcium acetate is on the order of about 10 to about 200 milliequivalents of calcium per dose.
- a typical dosage regimen of the inventive composition is about one tablespoon (about 15 mL) three times per day, which can be varied depending on the needs of the patient.
- the dose or quantity to be taken at a given time varies on an individual basis and can be adjusted as needed, for example by monitoring the serum levels of phosphorus and calcium.
- the inventive compositions are preferably administered close in time to food and/or beverage consumption.
- a dose of the inventive composition is taken orally just before meal ingestion and another dose is taken orally just after meal ingestion.
- the entire dose administered around a meal may all be taken just prior to ingestion of a meal.
- the individual to be treated is in need of dialysis treatment and hence may be undergoing such dialysis treatment.
- the individual is suffering from a renal disease, such as, for example, end stage renal disease or chronic kidney disease.
- Calcium acetate and a sweetener are dissolved in water. Flavoring and glycerin USP are mixed with each other to eventually obtain a homogeneous solution. A taste masking agent is added to and mixed with the calcium acetate solution. Parabens preservatives are dissolved in propylene glycol. Optionally an additional taste masking or sweetening agent is mixed with the calcium acetate solution. All solutions including any other polyols are agitated together and purified water is added q.s. to achieve a homogeneous solution.
- the % of sorbitol compound in the final composition is 21%.
- This composition contains about 0.5 calories per milliliter. Multiple people tasted this composition at typical dosage levels, and all people who tested this composition rated the composition as palatable and/or having "good" flavor. It was determined that this composition would be suitable for administration to patients and that those patients would be expected to comply well with their medication requirements, given the qualities of the composition (including but not limited to, palatability and low volume of liquid with high concentration of calcium). For those patients needing to limit calorie intake, this composition is suitable because of its low calorie content.
- the calcium acetate liquid composition of this example is formulated using 0.1% (w/v) methylparaben and 0.025% (w/v) propylparaben.
- the flavoring agents are added q.s. to achieve a palatable taste with the minimum effective amount of flavoring agent.
- the % of sorbitol compound in the final composition is 21%.
- This composition contains about 0.5 calories per milliliter. Multiple people tasted this composition at typical dosage levels, and all people who tested this composition rated the composition as palatable and/or having "good" flavor. It was determined that this composition would be suitable for administration to patients and that those patients would be expected to comply well with their medication requirements, given the qualities of the composition (including but not limited to, palatability and low volume of liquid with high concentration of calcium). For those patients needing to limit calorie intake, this composition is suitable because of its low calorie content.
- Example 4 Example 4
- Calcium acetate was dissolved in 1 liter of water and sucralose was added to this aqueous mixture, followed by the addition of maltitol with agitation, then glycerin, then Magnasweet with agitation and then Povidone was added and mixed until dissolved.
- Methylparaben was dissolved in propylene glycol and added to the aqueous mixture with agitation. The flavors were then added with agitation. Additional water was added to bring the total volume to 2 liters.
- This composition contains about 0.4 calories per milliliter. Multiple people tasted this composition at typical dosage levels, and all people who tested this composition rated the composition as palatable and/or having "good" flavor. It was determined that this composition would be suitable for administration to patients and that those patients would be expected to comply well with their medication requirements, given the qualities of the composition (including but not limited to, palatability and low volume of liquid with high concentration of calcium). For those patients needing to limit calorie intake, this composition is suitable because of its low calorie content.
Abstract
Description
Claims
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL07836163T PL2048948T3 (en) | 2006-07-21 | 2007-07-20 | Liquid compositions of calcium acetate |
NZ574331A NZ574331A (en) | 2006-07-21 | 2007-07-20 | Liquid compositions of calcium acetate |
ES07836163T ES2382993T3 (en) | 2006-07-21 | 2007-07-20 | Liquid calcium acetate composition |
JP2009520849A JP5335674B2 (en) | 2006-07-21 | 2007-07-20 | Liquid composition of calcium acetate |
EP07836163A EP2048948B1 (en) | 2006-07-21 | 2007-07-20 | Liquid compositions of calcium acetate |
AT07836163T ATE547099T1 (en) | 2006-07-21 | 2007-07-20 | LIQUID COMPOSITIONS MADE OF CALCIUM ACETATE |
AU2007275606A AU2007275606B9 (en) | 2006-07-21 | 2007-07-20 | Liquid compositions of calcium acetate |
CN200780034340.4A CN101522021B (en) | 2006-07-21 | 2007-07-20 | Liquid compositions of calcium acetate |
CA2658465A CA2658465C (en) | 2006-07-21 | 2007-07-20 | Liquid compositions of calcium acetate |
BRPI0714882-8A BRPI0714882A2 (en) | 2006-07-21 | 2007-07-20 | Calcium acetate liquid composition and use of an aqueous solution comprising from about 7% (w / v) to about 21% (w / v) calcium acetate |
MX2009000722A MX2009000722A (en) | 2006-07-21 | 2007-07-20 | Liquid compositions of calcium acetate. |
IL196584A IL196584A0 (en) | 2006-07-21 | 2009-01-19 | Liquid compositions of calcium acetate |
HK09109755.7A HK1129814A1 (en) | 2006-07-21 | 2009-10-21 | Liquid compositions of calcium acetate |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US83209306P | 2006-07-21 | 2006-07-21 | |
US60/832,093 | 2006-07-21 |
Publications (2)
Publication Number | Publication Date |
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WO2008011126A2 true WO2008011126A2 (en) | 2008-01-24 |
WO2008011126A3 WO2008011126A3 (en) | 2008-09-18 |
Family
ID=38957385
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2007/016415 WO2008011126A2 (en) | 2006-07-21 | 2007-07-20 | Liquid compositions of calcium acetate |
Country Status (18)
Country | Link |
---|---|
US (3) | US8591938B2 (en) |
EP (2) | EP2048948B1 (en) |
JP (1) | JP5335674B2 (en) |
KR (1) | KR101553719B1 (en) |
CN (2) | CN101522021B (en) |
AT (1) | ATE547099T1 (en) |
AU (1) | AU2007275606B9 (en) |
BR (1) | BRPI0714882A2 (en) |
CA (1) | CA2658465C (en) |
ES (1) | ES2382993T3 (en) |
HK (2) | HK1129814A1 (en) |
IL (1) | IL196584A0 (en) |
MX (1) | MX2009000722A (en) |
NZ (1) | NZ574331A (en) |
PL (2) | PL2048948T3 (en) |
RU (1) | RU2463060C2 (en) |
WO (1) | WO2008011126A2 (en) |
ZA (1) | ZA200900472B (en) |
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BE1019709A3 (en) * | 2010-12-22 | 2012-10-02 | Calxx Laboratoires S A | ORGANO-MINERAL FOOD PRODUCT AND PROCESS FOR PREPARATION |
GB2551971A (en) * | 2016-06-29 | 2018-01-10 | Syri Ltd | Taste masked liquid pharmaceutical composition of (RS)-4-(ethyl[1-(4-methoxyphenyl)propan-2-yl]am ino)butyl 3, 4-dimethoxybenzoate |
WO2020150460A1 (en) * | 2019-01-18 | 2020-07-23 | Milne Iii Donald A | Micronized aspirin formulation |
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- 2007-07-20 NZ NZ574331A patent/NZ574331A/en not_active IP Right Cessation
- 2007-07-20 CN CN200780034340.4A patent/CN101522021B/en not_active Expired - Fee Related
- 2007-07-20 JP JP2009520849A patent/JP5335674B2/en not_active Expired - Fee Related
- 2007-07-20 PL PL11192965T patent/PL2484352T3/en unknown
- 2007-07-20 AT AT07836163T patent/ATE547099T1/en active
- 2007-07-20 BR BRPI0714882-8A patent/BRPI0714882A2/en not_active IP Right Cessation
- 2007-07-20 US US11/878,169 patent/US8591938B2/en active Active
- 2007-07-20 AU AU2007275606A patent/AU2007275606B9/en not_active Ceased
- 2007-07-20 WO PCT/US2007/016415 patent/WO2008011126A2/en active Application Filing
- 2007-07-20 EP EP07836163A patent/EP2048948B1/en not_active Not-in-force
- 2007-07-20 CN CN201410289567.5A patent/CN104095838A/en active Pending
- 2007-07-20 CA CA2658465A patent/CA2658465C/en not_active Expired - Fee Related
- 2007-07-20 RU RU2009104774/15A patent/RU2463060C2/en not_active IP Right Cessation
- 2007-07-20 KR KR1020097003199A patent/KR101553719B1/en not_active IP Right Cessation
- 2007-07-20 EP EP11192965.9A patent/EP2484352B1/en not_active Not-in-force
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2009
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- 2009-10-21 HK HK09109755.7A patent/HK1129814A1/en not_active IP Right Cessation
-
2011
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2015
- 2015-04-10 HK HK15103511.7A patent/HK1202815A1/en unknown
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2441436A1 (en) | 2010-10-13 | 2012-04-18 | Fresenius Medical Care Deutschland GmbH | Easy to administer phosphate binder formulation |
WO2012048846A2 (en) | 2010-10-13 | 2012-04-19 | Fresenius Medical Care Deutschland Gmbh | Phosphate binder formulation for simple ingestion |
US9974805B2 (en) | 2010-10-13 | 2018-05-22 | Fresenius Medical Care Deutschland Gmbh | Phosphate binder formulation for simple dosing |
BE1019709A3 (en) * | 2010-12-22 | 2012-10-02 | Calxx Laboratoires S A | ORGANO-MINERAL FOOD PRODUCT AND PROCESS FOR PREPARATION |
GB2551971A (en) * | 2016-06-29 | 2018-01-10 | Syri Ltd | Taste masked liquid pharmaceutical composition of (RS)-4-(ethyl[1-(4-methoxyphenyl)propan-2-yl]am ino)butyl 3, 4-dimethoxybenzoate |
GB2551971B (en) * | 2016-06-29 | 2020-09-16 | Syri Ltd | Taste masked liquid pharmaceutical composition of mebeverine or pharmaceutically acceptable salts thereof |
WO2020150460A1 (en) * | 2019-01-18 | 2020-07-23 | Milne Iii Donald A | Micronized aspirin formulation |
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