WO2014138722A1

WO2014138722A1 - Process for the preparation of a non-corrosive base solution and methods of using same

Info

Publication number: WO2014138722A1
Application number: PCT/US2014/022203
Authority: WO
Inventors: Suzannah Jane ROBERTS; Stephanie Jo BLACKWELL; Shannon Joe BROWN
Original assignee: Cognate3 Llc
Priority date: 2013-03-08
Filing date: 2014-03-09
Publication date: 2014-09-12
Also published as: WO2014138723A3; WO2014138723A2

Abstract

The present invention provides novel methods of making a non-corrosive base solution for use as an alkalinity increasing agent and/or antioxidant. The present invention further provides novel compositions and methods which can be used to provide relief from acidosis, acidemia, and disorders related to or complicated by acidosis or excessive free radical or other reactive oxygen species production i n mammalian subjects.

Description

Process for the Preparation of a Non-Corrosive Base So lution

And Methods of Using Same

Related Appl ications

Th is appl ication claims priority benefit of United States Provisional patent application Serial No. 61 /774,622, filed March 8, 201 3 and United States Provisional patent appl ication Serial No. 6 1 /774,626, fi led March 8, 20 1 3, the disclosure of each which is incorporated herein in its entirety by reference.

Technical Field

The present invention relates to methods of making a non-corros ive base solution and the use of the non-corrosive base solution in mammal ian subjects. More speci fically, the present invention relates to methods and compositions for altering pU levels in mammal ian subjects.

Additional Disclosure Add itional disclosures relating to the instant application may be found in Un ited

States Provisional Patent application Serial No. 60/947,633, fi led J u ly 2. 2007, United States patent application Serial No. 12/ 1 67, 1 23. fi led July 2, 2008. now United States Patent 8,273,384, issued September 25, 201 2, and United States Provisional patent application 6 1 /757,059, fi led January 25, 20 1 , each of which is incorporated herein by reference in its entirety for all purposes.

Background fhe pi I, or hydrogen ion concentration, [ H+], is a logarithm ic measurement of the concentration of hydrogen in an aqueous solution. The lower the pi 1 is, the higher the concentration of hydrogen ion. Conversely, the higher the pi 1 is, the lower the concentration of hydrogen ion. The pH of natural environ ments varies from about

0.5 in the most acidic soils to about 1 0.5 in the most alkal ine lakes with most environments fal l ing somewhere in between. The range o f pH over which an organism grows is defined by the minimum pH, below which the organism cannot grow or reproduce; the maximum pH, above which the organism cannot grow or reproduce; and the optimum pH, at wh ich the organism grows best. For most organisms there is an orderly increase in growth rate and reproduction rate between the m in imum and the optimum pi 1 and a corresponding orderly decrease in growth rate and reproduction rate between the optim um and the maximum pH. reflecting the general effect of changing [11+] on the rates of enzymatic reaction.

I Under optimal conditions, the human body maintains very narrow pH ranges. The optimal pl l of blood in humans is maintained between a pH 7.3 to 7.4. For optimal heal th, the pH of blood should be about 7.365. The pH of urine can vary between 4.6 and 8, w ith a pH of 7 being norm and high levels of uric acid, i.e. a lower pU, indicating possible kidney disease, cancer, alcohol ism, liver disease, and l ipid disorders among others. The pH of sal iva is generally between 6.0 and 7.4 and increased acidity may be an ind icat ion of a diet h igh in acid ic or sugary foods.

An alteration in the optimal pH of any of these iluids may make an individual more susceptible to infection and disease by creating a more hospitable environment for m icroorganisms to grow.

The human body attempts to maintain optimal pH through the actions of buffers. respiration, and renal function. In dealing with the normal acid load from diet and metabol ism, bu ffers such as proteins, phosphate, and l-^C'C^ HCC - act to control the pH level. Respiration maintains a constant carbon ic acid level at 1 .2 meq/l or

PaCO₂ of 40 mm HG through either excretion or retention of C0₂ by the lungs.

Respiration can also rapidly compensate for changes in pl l by al tering the level of

PaCOi through the alteration of alveolar venti lation. The renal system

man ipulates the volume and composition of extracel lu lar fluid to help maintain the pi I of plasma. However, whi le the renal system can correct states of excess, it cannot correct states of deficiency such as through loss of Na+, + or I ICO ;

Additional ly, unl ike respiratory regulation, regulation of pH through renal function can take several days.

pl l levels can be affected by a number of exterior factors includ i ng, stress, diet. exposure to toxins, poor sleeping habits, and exercise. During acute stress, the heart rate and arterial blood pressure are increased, demand for oxygen is increased and lactic acid levels in the blood can rise by as m uch as 47%

(Vrij ikotte, 2000; and ubera, 201 2). All o f these events can contribute to a change in the pH of plasma. The Western diet can also affect pH levels. As an individual consumes more animal-based foods compared to plant-based foods, diets become more acid producing. (Strohle, 20 1 0) In the case of toxin exposure, individuals may have both metabol ic and respiratory acidosis. Metabol ic acidosis leads to alveolar hyperventilation with a fal l in PaCC>2 (partial pressure in CCb) . Toxin exposure can also decrease breathing rates leading to a decrease in the rate of CO2 expulsion from the lungs and respiratory acidosis . Sleep apnea can lead to elevated PaC0₂ (> 4:5 mm Hg) with acidemia (i.e., pH < 7.35) (B izzel, 2009). Even healthy pursu its can affect pH levels. As people exercise, heart rate, systolic blood pressure, and cardiac output increase. The body^' s metabolism becomes more active, producing CO2 and H⁺ and respiration increases to compensate for i ncreased oxygen demand. Eventual ly, an individual 's metabolism exceeds the body^' s oxygen supply and the body uses the lactic acid system (anaerobic glycolysis) to generate energy. These chem ical changes can cause the pH o f the blood to drop and (H+) to accumulate (Robergs, Gh iasvand, Parker 2004). The normal pi 1 of the m uscle cel l is 7. 1 but if the bui ldup of H+ continues and pi I is reduced to around 6.5 then muscle contraction may be impaired. (Garrett, 2000) When an indiv idual ^'s exercise intensity is sufficient to cross the lactic threshold, i .e. there is an abrupt increase in blood lactate levels, exercise becomes more di fficult. (Roberts & Robergs 1 997). Muscles ache and burn and become extremely fatigued. Symptoms increase i f the exercise continues making it d i fficult i f not i m possible to maintain exercise levels at the desired intensity. Fai lure or overloading of any of the body's normal regulatory mechanisms, whether through stress, pharmacological treatments, diet, or disease can cause acidosis, impacting an individual 's wel lbeing and qual ity of l i fe and leaving them more susceptible to infection and conditions such as cancer, card iovascular disease, fibromyalgia, hepatic disease, gout, arthritis, anem ia, sepsis, weight gain, staph infections including methici l lin-resistant Staphylococcus a areus, streptococcus, systemic inflammatory response syndrome, gout, arthritis, sepsis, d iabetic neuropathy, confusion, d iabetes, ce l lul itis and pancreatic impairment. There is therefore a need for compositions that can com pensate for the fai l ure of regulatory mechanisms to maintain physiological pH and preven t acidosis.

S mmary Provided herein are compositions and methods for mainta ining optimal p I I and treating or preventing acidosis. Compositions and methods as de scribed herein may further be used in the treatment of cond itions caused or exacerbated by acidosis, specifical ly lactic acidosis.

Acidosis may be accompanied by the buildup of lactate, particularly D-lactate. This buildup of lactate generally occurs when cells are hypoxic and functioning anaerobically. Impaired cel lular respiration leads to lower pH levels and can be indicative of tissue hypoxia, hypoperfusion and possible damage. Compositions and methods of the present invention increase pH levels, preventing or treating hyperlactemia (lactate concentrations between 2 mmol/L and 5 mmol/L) and lactic acidosis (lactate levels>5m mol/L and serum pi I <7.35).

Compositions and methods as described herein may addit ional ly be used for optimizing health and performance; preventing i l lness; decreasing recovery times from exertion, i llness, and inj ury; increasing energy level s; improving exercise performance; improving hydration; preventing muscle damage a fter exercise; and increasing stam ina during exercise. Compositions and methods described herein may further be used in the treatment and prevention of conditions caused by or exacerbated by having acidosis such as infections, cancer, arthritis, gout, sepsis and diabetes.

Compositions and methods as described herein may treat or prevent acidosis

a variety of means. In some embodiments, the compositions and methods of the present invention may decrease lactate levels, speci fical ly D-Iactate. The normal blood lactate concentration is 0.5- 1 mmol/L. I ndividuals in various disease states may have lactate concentrations of less than 2 mmol/L. Hyperlactem ia is defined as a m ild-to-moderate persistent increasing blood lactate concentration (2-5 mmol/L) without metabolic acidosis, whereas lactic acidosis is characterized by persistently increased blood lactate levels (usually >4-5 mmol/L) in association with metabol ic acidosis. The compositions and methods described herein are useful in the treatment and prevention of both hyperlactem ia and lactic acidosis. The normal pH of intracel lular and interstitial flu ids is maintained because acids are removed at the same rate they are added. If acid is added faster than it is removed, the pU of intracellular and interstitial fluids decreases, resulting in acidosis. Whi le stron g mineral bases have often been used to neutralize ac ids, they are very corrosive and are not general ly suitable for alteri g pH in living organ isms. The present invention provides compositions and methods for alteri ng base solutions so that they may be effectively used to increase pH levels in l iving organisms.

Reactive oxygen species including free radicals are produced as part of the normal metabolic process. They are generally prevented from causing damage through enzymes such as superoxide dismutases and catalases as wel l as antioxidants or other tree radical scavengers. When levels of OS exceed the neutralizing capacity of the body's regulatory mechanisms, such as during pe riods of intense exercise or due to a fai lure in endogenous antioxidant production, cellular damage, m utation and/or mortality levels increase. Proton absorbers which have previously been used to reduce free radicals are not true bases and require consumption of such large amounts that they are not general ly su itable for prolonged use.

The methods and formulations of the present invention provide a base solution (A lkaline w ater) with a high concentration of OH^" ions wh ich may be used as an alkal inity increasing agent, an antioxidant and/or free radical scavenger. I n some embodiments, the methods of the present invention comb ine a m agnetical ly treated calc ium hydroxide solution with an ozone treated sulf uric acid sol ution to create such a base solution with a h igh concentration of OH^" ions. The alkal ine water described herein may be taken internal ly and/or applied topically in dermatological formu lations.

Alkal ine water as described herein may be manufactured by whaxver means useful to create a water with a p I I between about 7 to about 14, preferably a i I of about 7.5 to about 12.75. preferably a pH of about 1 0 to about 1 1 , about 1 2 to about 14, about 12.25 to about 1 2.75, more preferably about 12.3 to about 1 3.8, preferably a pl l of about 12.5 to about 1 3.75.

In some embod iments, alkal ine water may be manufactured by combining oxides including, but not limited to, calcium hydroxide, calcium oxide, sodium hydroxide, sodi um oxide, potassium hydrox ide, potassium oxide, magnesium hydroxide, or magnesium oxide, with mineral free water to create a non-corrosive base solution with a h igh concentration of OH^" ions.

In some embodiments, the solution containing the oxide or hydroxide and water is stirred to increase a rate or amount of dissociation of the OH^" ions. After mixing, the ionic concentration in the water wi l l resu lt in a conductivity measurement of betw een about 0μ8/εηι to about 2000μ8/ατι, preferably between about Ι 00μ8/αη to about 1 000μ8/αη, preferably about 500 μ8/ατι to about 800μ8^/αη, preferably about 6 0 8/ειη to about 750μ8/αη, preferably about 700 μ8/αη to about 2000μ8/αη, preferably about 700μδ/α"η to about 750μ8/αη.

The resu lting concentrated alkaline water may be consumed directly or di luted with filtered water to a pH of about 7 to about 1 0, about 7.5 to about 8. The di luted alkal ine water wi ll have a conductivity of about 45μ8/ΰΐτι to about 90μ8/αη, about 50 nS/cm to about 75 ^iS/cm, about 50nS/cm to about 60μ8/αη. In some embodiments, the concentrated alkaline water may be used to make a gel for topical adm in istration.

Calcium hydroxide (Ca(OH)2) is a base wh ich may be used to create alkal ine water for use as an acid neutralizing agent and/or antioxidant as described herein. However, it will only dissociate slightly in a weak acid environment. At a pH of 5.5 or higher, calcium hydroxide rapidly loses its solubi l ity and at a pl l of 8.0 it is insoluble. In one embodiment, the present invention provides a method of increasing the solubility of calcium hydroxide al lowing a larger volume of

Ca(OI I)T to be dissociated in solution including weakly acidic, neutral or slightly basic solutions. In a further embod iment, the present invention provides a means of raising the pl l of a Ca(OH) solution at least one pl l point higher than a normal saturated calcium hydroxide solution. In some embodiments, the present invention provides a method of increasing the reactivity of Ca(OH)₂ in solution .

In another embodiment, the present invention provides a method for increasing the level of free hydroxide in a sol ution made with Ca(OH )₂ through the removal of calcium ions.

Useful forms of calcium hydroxide for use with in the formulations and methods of the invention include the forms described herein, as wel l as solvates, hydrates, or combinations thereof.

Su l furic acid is a strong m ineral ac id. In the compositions and methods of the present invention, sul furic acid in water is treated to reduce the ac idity wh i le maintaining the concentrat ion of sulfate in the solution. Such treatment may be accompl ished by any means possible, including the add ition of oxygen to the su l furic acid solution. In some embodiments, the sulfuric acid solution is in fused with ozone. Such treatments may increase the pH of the sulfuric acid solution, creating a neutral or basic solution which may then be combined with the calcium hydroxide solution described above to create a non-corrosive base solution with a high concentration of OH^" ions.

In another embodiment, calc ium oxide (CaO), another strong base, is used to form Alkaline water to be used as an acid neutral izing agent and/or antioxidant as described herein. Calcium oxide is stirred i nto puri fied, d isti lled , spring, filtered, or m ineral free water to create a non-corrosive base solution with a high concentration of OH^" ions. Such a solution wil l have a pH between about 7 to about 14, preferably a pH of about 12 to about 14, more preferably about 12.3 to about 1 3.8, preferably a pH of about 12.5 to about 1 3.75 and an ion ic

concentration such that the conductivity wou ld be about 5(^iS/crn to about 2()0C^S/cm, preferably between about Ι ΟΟμδ/ατι to about l OOOp S/cm, preferably about 50( S/cm to about 800μ8/ατι, preferably about 65l S/cm to about 750μ8/αη, preferably about 700μδ/ατι to about 750μδ/αη. In some em bodiments the ionic concentration is such that the conductivity may be between about 700μ8/αη to about 2000μ8/ΰΐτι.

The resulting concentrated alkaline water may be consumed directly or di luted with fi ltered water to a pi 1 of about 7 to about 1 0, about 7.5 to about 8. The di luted alkal ine w ater may have a conductivity of about 45μ8/απ to about 90μδ/αη, about 50μ8/αη to about 75 μδ/αη, about 50μ8/αη to about 60μ8/ατι. In exemplary embodiments, the compositions and method s described herein employ a base solution (also referred to as an 01 f solution or A lkal ine water) as described above to increase or maintain physiological pH in a mammal ian subject. Mammalian subjects amenable for treatment according to the formulations and methods of the invent ion include, but are not lim ited to. human and other mammalian subjects with acidosis, as wel l as conditions associated with or compl icated by ac idosis including, but not li m ited to, methici ll in resistant staphylococcus aureus (M RSA), streptococcus infections, sepsis, system ic inflammatory response syndrome (SI RS), fol l iculitis, gout, arthritis, hypoxia, hy poperfusion, hemorrhage, ethanol toxicity , shock, hepatic d isease, diabetic ketoacidosis, exercise fatigue, non-HodgkiiTs and Burki tt^' s lymphoma, system ic inflammatory response syndrome (SI RS), hyperventi lation, abdominal pain, lethargy, shock, severe anem ia, hypotension, irregular heart rhythm, tachycardia, fibromyalgia, weight gain, cancer, cardiovascular disease, respiratory disease, in fection, diabetes, diabetic neuropathy, cel l ul itis and pancreatic impairment. I n other embodiments, the compositions and methods of the present invention are used as anti-bacterial agents.

Mammalian subjects amenable for treatment accord ing to the formulations and methods of the inventi on further include, but are not l imited to, human and other mammalian subjects with symptoms of acidosis, as well as symptoms or conditions associated with or complicated by acidosis. Such symptoms include, but arc not lim ited to, acidem ia, extreme tenderness in the joint, inflammation, swel ling, pain, redness in the affected area, confusion, lethargy, rapid breath ing, shortness of breath, wheezing, chest pain or pressure, joint stiffness, swell ing, joint deform ity, crepitus, non-specific fever, joint inflammation, headaches.

fatigue, constipation, a fee ling of euphoria, nausea, seizures, coma, general ized weakness, abnormal heart function, decreased plate let count, areas of mottled skin, fever, low blood pressure, tachycardia, skin discoloration, irregu lar heartbeat, loss of appetite, jaund ice, abdom inal pain, easy bru ising, vom iting, ascites, dry sk in, dry mouth, low blood pressure, frequent urination, chest pain, lymph node pain, night sweats, skin rash, hyperventilation, abdominal pain, severe anemia, musculoskeletal pain, memory issues, and l ight headedness.

In some embodiments, the compositions and methods described herein may be used to speed recovery times, particularly from periods of stress or intense physical activ ity. In other embodiments, the compositions and methods described herein may be used to increase endurance, decrease lactic acid bui ld up, increase lactic ac id c learance, and increase musc le mass.

These and other subjects are effectively treated prophylactically and/or therapeutically by administering to the subject an effective amount of a base solution prepared using a hydroxide or oxide compound such as calcium hydroxide and/or calcium oxide. As noted above, the methods and formulations of the present invention may employ the oxide or hydroxide such as calcium hydroxide and/or calcium oxide in a variety of forms including solvates, hydrates, or combinations thereof in form ing the base solution.

I n some embodiments, alkal ine water may be taken in a concentrated formulation with a pl l of between about 1 2 to about 1 3.75, preferably about 1 2 to about 1 2.5 and a conductivity of about 700μ8/αη to about 200(^S/cm, preferably about 70(^Scm to about 1 500μ8/αη, preferably about 700μ8Λ:ιη to about 1000μ8/ατι, more preferably a out700μS/cm to about 750μ5/ατι. I n other embod iments, Alkal ine water as described herein may be diluted with water to a pH of about 6.9 to about 7.5. preferably about 6.9 to about 7.2, more pre ferably about 7.0 and a conductiv ity 45 μ£/ατι to about 60μ5/αη, preferably about 5(^S/cm to about 55 μ8/αη. Any type of water that will lower the pH may be used for the dilution including, but not limited to, tap, spring, disti l led, reverse osmosis, charcoal filtered, mineral-free, or filtered water. Within additional aspects of the invention, a composition made using the base solution and additional agents may be combinatorial ly formulated or coord inatelv adm inistered to yield an effective alkal izing treatment. The com positions and methods of the present invention provide certain advantages in regulating pH in a mammal ian subject. The combination of a composition made us ing calcium hydroxide, calcium oxide or a solvate or hydrate thereof and an additional alkalinity increasing agent will yield an enhanced therapeutic response beyond the therapeutic response el icited by either agent alone.

Usefu l secondary or additional agents for use within the formu lations and methods of the present invention inc lude, but are not l imited to, alkalinity increasing agents, adaptogens, amino acids and amino acid derivati ves, anti-inflammatory agents, anti-nausea agents, analgesics, antioxidants, aphrod isiacs, detoxifying agents, dietary supplements, herbal supplements, calm ing agents, herbs and plant extracts, essential nutrients, coenzymes, electrolytes, energy boosters, essential trace elements, flavonoids, hormones, imm une boosters, neurotra nsm itters, essential fatty acids, memory enhancers, vitamins and m inerals, protein, sedatives, stimu lants and nutritional supplements for use within the formulations and methods described herein.

For example, useful secondary or additional therapeutic agents including alkal in ity increasing agents for use within the formulations and methods of the present i nvention incl ude sod ium bicarbonate; a carbonate, a phosphate, or a hydroxide of sodium or potassium; magnesium carbonate; magnesium hydroxide; ammonium carbonate ; ammon ium bicarbonate; magnesium oxide; sodium or potassium citrate, bicarbonate, sulfate, and benzoate; ascorbate; calcium carbonate; any pharmaceutically acceptable material that causes the pi 1 of an aqueous med ium to rise above pi I 7.0, or mixtures thereof

The compositions described herein may additionally contain sweeteners, stabi lizers, flavoring, anti-caking agents, flavor protectants, preservatives, anti- foam ing agents, colorants, emulsi fiers, th ickeners and the l ike.

The compositions described herein may be consumed internally or appl ied topical ly. In some embodiments, the compositions described herein may be applied topical ly in the form of gels, creams, lotions, milks, waxes, water-in-oil or oi l-in water emulsions, sprays, suspensions, c leansing products, hair care products and the l ike. In some embodiments, the alkal izing treatment may be administered in combination with therapeutic agents other than additional alkal inity increasing agents. Such combinations may increase the effectiveness of therapeutic agents used to treat particular d iseases or conditions such as cancer. In further embodiments, such combinations may decrease the required effective amount of the other therapeutic agents. In some embodiments, the a lkal izing treatment may facilitate the adm inistration of therapeutic agents or organic substances which are vulnerable to acidic condit ions such as those found in the stomach. Additional therapeutic agents that may be adm in istered to treat or prevent ac idosis and conditions assoc iated with acidosis inc lude, but are not lim ited to. probenec id, al lopurinol, nonsteroidal anti-inflammatory drugs (NSA I Ds), colchicine, corticosteroids, uricosuric agents, xanthine oxidase inhibitors, losartan, fenofibrate. duloxeti ne, mi lnacipran, urate oxidase. Y-700, COX-2 inhibitors, analgesics, corticosteroids, disease-modifying anti-rheumatic drugs, antibiotics. vasodepressors, sulfasalazine, radiation therapy, chemotherapy , and benzaldehyde derivatives such as those described in U.S. Patent Appl ication No. 12/4 1 8,342, i ncorporated by reference herein in its entirety.

The compositions of the present invention are further effective in preventing secondary infections in mammal ian subjects with comprom ised immune systems, such as those subjects suffering from chronic diseases such as cancer or H I V.

In additional exemplary embod iments, the compositions and methods of the invention employ an OH^" composition made from m ineral hydroxides and oxides including, but not lim ited to, calcium hydroxide and/or calcium oxide as an antioxidant and free radical scavenger, providing certain, advantages in regulating free radical and other ROS levels in a mammal ian subject.

Mammal ian subjects amenable for treatment accord ing to the formulations and methods of the invention further include, but are not limited to, human and other mammalian subjects in need of antioxidant treatment or ROS reduction or management, incl uding those suffering from conditions associated w ith or compl icated w ith excess free radicals such as gout. Lesch-Nyhan syndrome. hemochromatosis, Alzheimer' s disease, amyotrophic lateral sclerosis, arthritis, atherosclerosis, cancer, cataracts, chronic obstructive pulmonary disease, diabetes, diabetic neuropathy, coronary artery disease, heart failure, hypertension, inflammatory bowel disease, macular degeneration, multiple sclerosis, Parkinson's disease, fibromyalgia, Reynaud's phenomenon, cellul itis, methicil l in- resistant Staphylococcus aureus (MRSA), streptococcus, hepatitis C and reperfusion inj ury. In addition, the compositions of the present invention have proven effective in the treatment of skin conditions such as psoriasis, Morgellons d isease, and fungal infections including but not l imited to candidiasis, tinea cruris, and tinea pedis.

These and other subjects are effectively treated prophylactically and/or therapeutically by administering to the subject a free radical reducing effective amount (antioxidant effective amount) of an OH^" solution made from a hydroxide or oxide such as calc ium hydroxide or calc ium oxide as described herein alone or i n combination w ith a secondary antioxidant agent or add itional therapeutic agent. As noted above, the methods and formulations of the present invention may employ calcium hydroxide and/or calcium oxide in mak ing the OH^" solution and/or an additional antioxidant agent in a variety of forms i ncluding solvates. hydrates, or combinations thereof.

The foregoing and other objects, features, aspects and advantages of the present invention wi ll become more apparent from the following detai led description o f the invention and examples, which are intended to exempl ify non-l im iting embodiments of the i nvention.

Detailed Description

Novel methods and compositions have been provided herein for maintaining optimal ρϊ I and treating or preventing acidosis, symptoms of acidosis, and conditions caused by or exacerbated by acidosis. The present invention provides a non-corrosive strong base solution (also referred to as an OH^" sol ution, a base solution or Al kal ine water) and methods for using the solution for the regulation of physiological pl l in vertebrates, inc luding mammals.

The compositions and methods provided herein are suitable for optim izing health and performance; preventing illness; decreasing recovery times from exertion, i llness, and inj ury; increasi ng energy levels; improving exercise performance; improving hydration; preventing musc le damage after exercise; and increasing stam ina during exerci se.

Mammalian subjects amenable for treatment according to the formulations and methods of the invention include, but are not limited to, human and other mammalian subjects with acidosis, as well as conditions assoc iated with or complicated by acidosis including gout, abdominal pain, Alzheimer^'s disease, amyotrophic lateral sclerosis, fungal infections including but not limited to candidiasis, arthritis, atherosclerosis, cancer, cardiovascu lar disease, cataracts, cellul itis and pancreatic impairment, chronic obstructive pulmonary d isease, coronary artery d isease, diabetes, diabetic ketoacidosis, ethanol toxicity, exercise fatigue, folliculitis, gout, heart failure, hemochromatosis, hemorrhage, hepatic disease, hepatit is C, hypertension, hyperventilation, hypotension, hypoxia and hypoperfusion, infection, inflammatory bowel disease, irregular heart rhythm, Lesch-Nyhan syndrome, lethargy, macular degeneration, methici l lin resistant staphylococcus aureus (MRSA), Morgellons disease, fibromyalgia, multiple sclerosis, nausea, non-1 lodgkin' s and Burkitt's lymphoma, systemic inflammatory response syndrome (SI RS). Parkinson^' s disease, psorias is, regional

hypoperfusion, pancreatic impairment, reperfusion inj ury, respiratory disease, Reynaud's phenomenon, sepsis, severe anem ia, shock, tachycard ia, tinea cruris, tinea ped is, vom iting and weight gain. In other embodi ments, the compositions and methods of the present invention are used as anti-bacterial agents.

Mammalian subjects amenable for treatment accord ing to the formulations and methods of the invention further include, but are not l iiriited to. human and other mammalian subjects with symptoms of acidosis, as well as symptoms or conditions associated with or compl icated by acidosis. Such symptoms include, but are not l imited to, acidem ia, extreme tenderness in the joint, inflammation, swel l ing, pain, redness in the affected area, confusion, lethargy, rapid breathing, shortness of breath, wheezing, chest pain or pressure, joint stiffness, swell ing, joint deform ity, crepitus, non-specific fever, joint inflammation, headaches, fatigue, a feeling of euphoria and nausea, seizures, coma, generalized weakness, abnormal heart functi on, decreased platelet count, areas of mottled skin, fever, low blood pressure, tachycardia, skin discoloration, irregular heartbeat, loss of appetite, jaundice, abdom inal pain, easy bruising, vomiting, ascites, easy bruising, dry skin, dry mouth, low blood pressure, frequent urination, chest pain, lymph node pain, night sweats, skin rash, hyperventilation, constipation, severe anemia, memory loss, mood swings, musculoskeletal pain and l ight headedness. I n some embodiments, the compositions and methods of the present invention may be used to speed recovery times, particularly from periods of stress or intense physical activity.

The present invention additionally provides methods of using the non-corrosive strong base solution (also referred to as an OH^" solution, a base solution or

A lkal ine water) as an antioxidant as further described in related U.S. Patent Application No. 12/ 1 67, 123 fi led July 2, 2008 wh ich claims priority benefit of U .S. Provisional Patent Appl ication No. 60/967,633 fi led July 2, 2007.

The antioxidant compositions described herein may be used in the reduction of reactive oxygen species in vertebrates, including mammals. Reduction of fi ce rad icals and other reactive oxygen species (ROS) is effective in the treatment of diseases includi ng, but not limited to, gout, abdominal pain. Alzheimer' s di sease, amyotroph ic lateral sclerosis, arthritis, atherosclerosis, cancer, cardiovascular d isease, cataracts, cel lul itis and pancreatic impairment, chron ic obstructive pulmonary disease, coronary artery disease, diabetes, diabetic ketoacidosis.

ethanol toxicity, exerc ise fatigue, foll icul itis, gout, heart fai lure, hemochromatosis, hemorrhage, hepatic disease, hepatitis C, hypertension, hyperventi lation, hypotension, hypoxia, hypoperfusion, infection, in flammatory bowel disease, irregular heart rhythm . Lesch-Nyhan syndrome, lethargy, macular degeneration. meth icil lin resistant staphylococcus aureus ( RSA), fibromyalgia, multiple sclerosis, nausea, non-Hodgkin ^'s and Burkitt^'s lymphoma, Parkinson ^'s disease, system ic inflammatory response syndrome ( S I RS), psoriasis, regional

hypoperfusion, pancreatic impairment, reperfusion inj ury, respiratory disease, Reynaud ^'s phenomenon, sepsis, severe anem ia, shock, tac hycardia, vomiting and weight gain.

Another embodiment of the present invention provides methods for treating skin conditions and infections in vertebrates, including mammals, including cond itions such as, but not l imited to, rnethicillin-resistant Staphylococcus aureus (MRSA), psoriasis, Morgel lons disease and fungal infections including but not l im ited to candidiasis, tinea crur is, and tinea pedis.

A further embodiment of the present invention provides a strong base solution (also referred to as an OH^" solution, a base solution or Alkal ine water) for use in the prevention of secondary infections in vertebrates, including mammalian subjects; particularly mammal ian subjects with comprom ised immune systems, such as those subjects suffering from chronic diseases such as, but not l imited to, cancer or H IV, or whose immune systems are compromised due to treatments for diseases such as cancer.

An additional embodiment of the present invention provides methods of using the strong base solution to increase the effectiveness of other pharmaceutical agents.

The use of the strong base solution neutralizes stomach and other body acids, al lowing for increased absorption of certain medications that w ould otherwise be destroy ed or weakened during ingestion.

For the purposes of describing the present invention, the following terms and definitions are provided by way of example. Additional terms and definitions for describing embodiments of the present invention are provided by way of example elsewhere in the application.

As used herein, "mic robial" refers to any microorganism capable of causing d isease. Such m icroorganisms include fungal, viral and bacterial m icroorgan isms. By the term "ef fective amount" of a compound is meant a non-toxic but sufficient amount of the compound to provide the desired function, i.e., as an anti-infective, as an antioxidant, or as an alkal izing agent. An appropriate effective amount may be determ ined by one of ordinary ski ll in the art using only routine

experimentation.

formu lations and methods herein employ an OH^" solution made from an oxide or hydroxide such as calcium hydroxide or cal cium oxide alone or with an add itiona l or secondary therapeutic agent for the regulation of physiological pi 1. Within these formulations and methods, the secondary agent may be provided in any of a variety of forms, incl uding any polymorphs, enantiomers, pharmaceutical ly acceptable salts, solvates, hydrates, or combinations thereof Such combinations of an OH^" composition and secondary agent may be administered either combinatorial !)/ or coord inately as disclosed herein to effectively treat mammal ian subjects with acidosis as wel l as compl ications associated with acidosis such as increased infection, cancer, diabetes and pancreatic impairment. Useful secondary or additional agents for use within the formulations and methods of the present invention include, but are not limited to, alkal inity increasing agents, adaptogens, amino acids and amino acid derivatives, anti-inflammatory agents, anti-nausea agents, analgesics, antioxidants, aphrodisiacs, detoxifying agents, dietary supplements, herbal supplements, calming agents, herbs and plant extracts, flavorings, essential nutrients, coenzymes, electrolytes, energy boosters, essential trace elements, flavonoids. hormones, immune boosters, neurotransm itters, essential fatty acids, memory enhancers, vitamins and m i nerals, protein, sedatives, stimulants and nutritional supplements for use within the form ulations and methods described herein. Within these formulations and methods, the secondary agent may be provided in any of a variety of forms, including any poly morphs, enantiomers. pharmaceutically acceptable salts, solvates, hydrates, or

combinations thereof. Such combinations o f an Ol Γ composition and secondary agent may be admini stered either combinatorial ly or coordinately as disclosed herein to effectively treat or prevent acidosis and conditions or symptoms caused by or exacerbated by acidosis.

Formulations and methods herein may additionally employ a base solution as an antioxidant or free radical scavenger for the regu lation of ROS levels i ncl uding free radical levels. Within these formulations and methods, the oxide or hydroxide such as calc ium hydroxide or ca lcium oxide used to produce the OH solution may be prov ided in any of a variety of forms, inc luding solvates, hydrates, or combinations thereof Formulations containing a non-corrosive strong base solution made from calcium hydroxide or calcium ovide as d isclosed herein are effectively used to treat mammal ian subjects suffering from an over accumulation o f free radicals as wel l as diseases and cond itions associated with free rad icals including, but not l im ited to gout, Lesch-Nyhan syndrome, hemochromatosis, Alzheimer^'s disease, amyotroph ic lateral sclerosis, arthritis, atherosclerosis, cancer, cataracts, chronic obstructive pulmonary disease, d iabetes, coronary artery disease, heart fai lure, hypertension, inflammatory bowel disease, macular degeneration, mu ltiple sclerosis, Parkinson^'s disease, Raynaud' s phenomenon, hepatitis C, cel lul itis, methici ll in-resistant Staphylococcus aureus, reperfusion inj ury, an d skin conditions including, but not lim ited to, psoriasis, fol l icu l itis. orgellons disease, candidiasis, tinea cruris, and tinea pedis.

Formulations and methods herein may also employ an OH^" composition made from an oxide or hydroxide such as, but not l im ited to, calcium hydroxide and/or calcium oxide alone or with an additional antioxidant agent as an antioxidant or free radical scavenger. Within the methods and compositions of the invention, a base solution alone or in combination with a second therapeutic agent such as an antioxidant agent or their derivatives are effectively formulated or adm inistered as an antioxidant.

Additional therapeutic agents for use within the compositions of the present invention include antioxidants including, but not limited to, xanthine oxidase inhibitors including, but not lim ited to al lopurinol and fol ic acid; NADPH oxidase inhibitors, including, but not limited to, adenosine; calci um channel blockers; superoxide dismutases; catalases; album in; i nhibitors of iron redox cycl ing, including, but not lim ited to deferoxam ine, apotransferin and ceruloplasm in; beta carotene; ascorbates; myricetin-3-O-galactoside, quercit in-3-O-galactoside; and alpha tocopherol.

Formulations and methods for use as an alkal izing agent, antioxidant or ROS scavenger as described herein may additional ly employ therapeutic agents such as, but not l im ited to, probenecid, al lopurinol. nonsteroidal anti-in flammatory drugs (NSA I Ds), colchicine, corticosteroids, uricosuric agents, xanthine oxidase inhibitors, losartan, fenofibrate. urate oxidase, Y-700, COX-2 inhibitors, analgesics, corticosteroids, disease-mod ifying anti-rheumatic drugs, antibiotics, vasodepressors, sulfasalazine, rad iation therapy, chemotherapy, duloxetin, m i lnacipran, gabapentin, pregabal in, and benzaldehyde derivat ives such as those described in U . S. Patent Appl ication No. 1 2/4 1 8,342, incorporated herein by reference in its entirety.

A broad range of mammal ian subjects, including human subjects., are amenable for treatment using the formulations and methods of the invention. These subjects include, but are not lim ited to, human and other mammal ian subjects with acidosis and/or excessive free radical production as wel l as those suffering from conditions or compl ications of having acidosis including increased susceptibil ity to m icrobial infections or other secondary in fections; skin infections such as, but not l im ited to. MRSA; psoriasis; orgellons disease; and fungal infections such as cand idiasis, tinea cruris, and tinea ped is. Additionally amenable to treatment are mammals including humans in need of antioxidant treatment or free radical el im ination, including those suffering from conditions or compl ications associated with excess free radicals, including, but not l im ited to, gout, Lesch-Myhan syndrome, hemochromatosis, Alzheimer's disease, amyotrophic lateral sclerosis, arthritis, atherosclerosis, cancer, cataracts, chronic obstructive pul monary disease, diabetes, cellulitis, coronary artery disease, heart failure, hypertension, inflammatory bowel disease, macular degeneration, multiple sc lerosis, Parkinson's disease, Reynaud's phenomenon, hepatitis C, reperfusion injury, MRSA, sepsis, folliculitis, gout, arthritis, hypoxia, hypoperfusion, hemorrhage, ethanol toxicity, shock, hepatic disease, diabetic ketoac idosis, exercise fatigue, non-Hodgkin's and Burkitt^'s lymphoma, nausea, vom iting, hyperventilation, abdom inal pain, lethargy, shock, severe anemia, systemic inflammatory response syndrome (SI RS), hypotension, irregu lar heart rhythm, tachycardia, weight gain, fibromyalgia, cardiovascu lar disease, respiratory disease, infection, diabetes, cel lul iti s and pancreatic impairment and infection.

Mammalian subjects amenable for treatment according to the formu lations and methods of the invention further include, but are not limited to, human and other mammal ian subjects with symptoms of acidosis, as well as symptoms or conditions associated with or complicated by acidosis. Such symptoms include, but are not l im ited to, acidemia, extreme tenderness in the joint, in flammation, swel ling, pain, redness in the affected area, confusion, lethargy, rapid breathing, shortness of breath, wheezing, chest pain or pressure, joint stiffness, swell ing, joint deform ity, crepitus, non-speci fic fever, joint inflammation, headaches, fatigue, a feel ing of euphoria and nausea, seizures, coma, genera l ized weakness, abnormal heart function, decreased platelet count, areas of mottled skin, fever, low blood pressure, tachycardia, skin discoloration, irregular heartbeat, loss of appetite, jaundice, abdom inal pain, easy bru ising, vomiting, ascites, easy bruising, dry skin, dry mouth, low blood pressure, frequent urination, chest pain, lymph node pain, night sweats, skin rash, hyperventi lation, constipation, severe anemia, memory loss, mood swings, musculoskeletal pain and l ight headedness.

Alkal ine water, or water with a high concentration of OH^" ions as described herein may be manufactured by any means general ly used. In some em bodiments, alkal ine water may be manufactured by combining oxides and hydroxides including, but not lim ited to, calcium hydroxide, calcium oxide, sodium hydroxide, sodium oxide, potassium hydroxi de, potassium oxide, magnesium hydroxide, or magnes ium oxide, with water to create a non-corrosive base solution with a high concentration of OH^" ions. The water may be tap, spring, m ineral-free, fi ltered, purified, distilled, or any other suitable water w ith a low m ineral concentration. In some embodiments, the OH^" solution of the present invention may be formed through the dissolution of calcium hydroxide in water. In some embodiments, the calci um may be betw een 2% and 1 0% mole weight, preferably between 2% and 6% mole weight, more preferably 4% mole weight in water. Dissoc iation of the calcium hydroxide in water may be facilitated by any means appl icable. In some embodiments, the cal cium hydroxide solution may be agitated. I n other embodiments, the cal cium hydroxide solution may be exposed to a magnetic field. I n further embodiments, the calcium hydrox ide solution may be agitated whi le being exposed to a magnetic field.

Such manipulation of the solution wi l l yield substantial d issolution of the calci um hydroxide, creating a supersaturated solution. In some embodiments, substantial dissolution is such that the dissociation of the calcium hydroxide is increased to between 50% and 95% of maximum dissoc iation, preferably between 50% and 75% of maximum dissociation, more preferably between 75% and 95% of maximum dissociation, in some cases greater than 95% d issoc iat ion. By maximum dissociation is meant that when additional calcium hydroxide is added to the solution at a given temperature or pressure, the ca lci um hydroxide precipitates out regardless of the length of t ime or add itiona l agitation. I n some embodiments, agitation of the calcium hydroxide solution in a magnetic field increases the pH of the calcium hydroxide solution to at least one pi 1 unit h igher than a normal saturated Ca(OI 1)2 solution, preferably 1 to 3 poin ts h igher than a normal saturated Ca(OH)2 solution. I n further embodiments, agitating the solution in a strong magnetic field increases the solubi l ity of the Ca(OI I); to greater than normal, preferably 2-200 times greater than normal, more preferably 50 to 1 00 times greater than normal, preferably 1 00 times greater than normal.

The magnetic field to which the calcium hydroxide solution is exposed may be generated by any means applicable. In some embodiments, the magnetic field may be generated by magnets, magnetic water treatment units or other magnetic field generating apparatus. Such magnetic field generating apparatus may be composed of one or a plurality of magnets wh ich may surround, be placed around, or be otherwise disposed of adjacent to the container containing the Ca(OH)2 solution. Any kind of magnet or apparatus that creates a strong magnetic field may be used. Magnets which may be used as part of magnetic water treatment units or to otherwise generate a magnetic field include, but are not lim ited to, NdFeB (Neodym ium -Iron-Boron), Ferritc, A IN iCo (Alum inum-Nickel-Cobalt), SmCo (Samarium Cobalt), Alcomax (al loy of iron, nicke l, alumi nium, cobalt and copper), Cunife (copper, nickel and iron or copper, nickel, iron and cobalt), and Fernico (iron, nickel, cobalt) magnets. The magnets may be monopolar or bipolar. In other embodiments, the magnetic field generating apparatus may comprise electromagnets. In additional embodiments, the magnets may be encased in a housing. Such housi ng may be made of any material appl icable, including, but not limited to, metals such as, but not lim ited to, alum inum, or steel, and plastics, or any combination thereof. I n some embodiments, magnets on opposing sides of the container holding the solution may have opposite poles such that, lor example, the positive and negative poles face each other. In other embodi ments, the magnets may rotate a round the container of calcium hydroxide solution.

In order to increase the OH^" concentration of the calcium hydroxide solution, it may be combined with a solution made from sulfuric acid. In order to create the solution made from sul furic ac id, sulfuric ac id is added to water. In some embod iments, enough sulfuric ac id is added to water to create a solution of equal molar strength to the Ca(OI 1)2 in the calcium hydroxide solution In other embodiments, the concentration of the solution will be about 0.02% to about 0.08 % acid in water by volume, preferably about 0.04% to about 0.06% acid in water by volume. I n further embodiments the concentration may be about 50- 1 00m L of sulfuric acid (Bauine 1 2°) per gal lon of water, preferably about 70mL to about 80 m l, more preferably about 70 to about 78 inL of sul furic acid per gallon of water. In some embodiments, the sul furic acid solution may be agitated unti l substantial d issociation occurs such that 75% to 1 00 % of maximum dissociation is achieved, preferably 75% to 95% of maximum dissoc iation, more preferably 80% to 95% of maximum dissociation of sulfuric acid, in some instances greater than 95% dissociation of sulfuric acid.

In some embodiments, it may be desirable to reduce the acidity of the sulfuric acid sol ution. The reduction of acidity may occur through any means appl icable. In some embodiments, the reduction of acidity may occur through the introduction of additional oxygen to the solution. I n one embodiment, nascent oxygen may be introduced into the sulfuric acid solution. I n another em bodiment, the sulfuric acid solution may be treated with ozone by circulating the solution through ozone generators. The ozone generators dissociate an oxygen wh ich is consumed by (2 H+) ion(s) in the acid solution to create water. The acid solution may be rec irculated through the ozone un its unti l a particular concentration of oxygen is absorbed or a particular pH is achieved. In some embodi ments, the sulfuric ac id solution will be run through the ozone generators until the pH increases by at least I to 6 points, preferably at least 1 to 4 points, more preferably at least 2 to 3 points. In some embodiments, the sulfuric acid solution wi l l be circu lated through ozone generators unti l the pi I reaches or exceeds about 7.0. The neutral ized acid solution may then be slowly added to the calcium hydroxide solution to form a resultant m ixture. The free calcium in the calcium hydroxide so l ution wi l l react with the sul fate ions (SO₄ ² ) in the acid solution to create insoluble anhydrous calcium sul fate precipitate. The mixture may then be agitated unti l the reaction goes to completion and the anhydrous calcium sul fate may be til lered or otherwise removed from the solution . In some embodiments, a non -ionic surfactant may be added to the resulting m ixture in order to enhance prec ipitation. Such non-ionic surfactants may include, but are not limited to, linear or nonyl-phenol alcohols or fatly acids, alcohol ethoxylates, alkylphenol ethoxylates, alky 1 polyglycosidcs, alkyl ethers such as polyoxyethylene octyl ether, polyoxyethylene lauryl ether, polyoxyethylene stearyl ether, and polyoxyethylene olcyl ether; alkyl phenyl ethers such as polyoxyethylene octylphenyl ether, and pol yoxyethylene nonylphenyl ether; alkyl esters such as polyoxyethylene laurate. polyoxyethylene stearate, and polyoxyethylene oleate; alkylamines such as polyoxyethylene laurylamino ether, polyoxyethylene stearylamino ether, polyoxyethy lene oleylam ino ether, polyoxyethylene soybean am ino ether, and polyoxyethylene beef tal low am ino ether; alkylamides such as polyoxyethylene lauric am ide, polyoxyethylene stearic am ide, and polyoxyethylene oleic am ide : vegetable oil ethers such as polyoxyethylene castor oi l ether, and polyoxyethylene rapeseed oi l ether; alkanolam ides such as lauric acid diethanolam ide, stearic acid

diethanolam ide. and oleic acid diethanolam ide; and sorbitan ester ethers such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalm itate, polyoxyethylene sorbitan monostearate, and polyoxyethylene sorbitan monooleate.

In some embodiments, calc ium oxide (CaO), another strong base, is used to form the acid neutralizing agent and/or antioxidant. Calcium oxide is stirred into purified, disti lled, or mineral free water to create a non-corrosive base solution with a high concentration of OH^" ions.

In some embodiments, the calcium may be between 2% and 1 0% mole weight, preferably between 2% and 6% mole weight, more preferably 4% mole weight in water. Dissociation of the calcium oxide in water may be facilitated by any means appl icable. In some embodiments, the calcium oxide solution may be agitated. Such a calcium oxide solut ion wil l have a p.H between about 7 to about 14, preferably a pH of about 12 to about 14, more preferably about 1 2.3 to about 1 3.8, preferably a pH of about 1 2.5 to about 1 3.75 and an ionic concentration such that the conductivity would be about 50μ8/αη to about 2000μ 8/ατι, preferably between about Ι 00μ8/αη to about Ι 000μ8/αη, preferably about 500μ8/αη to about 800μ8/αη. preferably about 650μ8/ο η to about 750μ8/αη, preferably about 700μ8/αη to about 750μ8/αη. In some embodiments, the ion ic concentration is such that the conductivity is between 700μ8/αη to about 2000μ8/αη.

The resulting concentrated alkal ine water may be consumed directly or di luted with water to a pH of about 7 to about 10. about 7.5 to about 8. The di luted alkal ine water may have a conductivity of about 45 μ8/αη to about 90μ8/αη, about 50μ8/αη to about 7 μ8/αη, about 50^iS/cm to about 60μ8/αυ. I n some embodiments, the water may be non-chlorinated. In other embodiments, the water may be spring water. In further embodiments, the water may be disti l led. In yet another embodi ment, the water may be mineral-free water. In additional embodiments, the water may be generated by an alkaline water machine.

In some embodiments, alkal ine water may be taken in a concentrated formulation with a pH of between about 12 to about 1 3.75, preferably about 1 2 to about 12.5 and a conductivity of about 700μ8/αη to about 2000μ8/αη. preferably about

700μ8ατι to about 1 500μ8/αη, preferably about 700μδΛ;ηι to about Ι 000μ8/ατι, more preferably about 700μ8/ατι to about 750μδΛ;ιτι. In other embodiments, A lkal ine water as described herein may be diluted with purified, distil led, tap. spring, non-chlorinated, or mineral free water to a pH of about 6.9 to about 7.5. preferably about 6.9 to about 7.2, more preferably about 7.0 and a conductivity

45μδ/αη to about όθμδ/αη, preferably about 50μ8/ειη to about 55 μ8Λ η.

In some embodiments, the solution, however formed, may be filtered at various stages to remove particulates. For example, the calcium hydroxide solution may be fi ltered prior to combining with the sulfuric ac id solution and/or the resultant mixture may be filtered to remove particulates. In other embodiments, the resultant mixture may be additionally cooled or partial ly frozen lo create a slurry and further purified, for example through filtration. I n one embodiment, the resulting mixture is cooled to below about 36"F. In another embodiment the resulting mixture is cooled to below about 36 but above about 35 ^° F.

In some embod iments, the concentrated OH sol ution prepared by combining the calcium hydroxide solution and sulfuric acid solution or d issolut ion of calcium oxide may be diluted with water to reach a specified pH prior to consumption or administration. I n some embodiments, the water may be non-chlorinated. In other embodiments, the water may be spring water. In further embod iments, the water may be disti lled. In yet another embodiment, the water may be mineral free water. In additional embodiments, the water may be generated by an alkal ine water machine. In some embodiments, the resulting m ixture may be diluted to a pH of between about 8.0 to about 1 1 , more preferably between about 8.5 to about 9.5. more preferably between 8.5 to about 9.0. This solution may then be used lo e ffectively neutral ize acids, to treat acidosis, prophylactical ly. to reduce free radicals, and/or as an antioxidant.

The acid/alkal ine balance in a healthy mammal is general ly regulated through the actions of buffers, respiration and renal function. Two forms of acid are generated as a result of normal metabolic processes. Oxidative metabol ism produces a large amount of C0₂ daily which is excreted through the lungs. The other form of acid results from the metabol ism of d ietary protein, resulting in the accumulation at an average rate of approximately 1 mmol per ki logram of body weight, or 50 to 70 mmol per day of acid in an average adult on a typical Western meat containing d iet.

The most important mechanism preventing change in the pi I of extracel lular fluid is the carbonic acid/bicarbonate buffer system . The importance of this buffer pair relates to certain key properties: bicarbonate is present in a relatively high concentration in the extracellular fluid (between 24 and 28 mmol/L) and the components of the buffer system are effectively under physiological control: the

CO2 by the lungs, and the bicarbonate by the kidneys. Λ shift in pH can be brought about by either a primary change in the bicarbonate concentration (metabolic disturbances) or in the partial pressure of C0₂ in the blood (respiratory disturbances). Respiratory acidosis results from the accumulation of C0₂ in the body as a result of fai lure of pulmonary venti lation. This may occur from lesions either in the central nervous system (e.g. depression of cerebral function, spinal cord injury), in the peripheral nervous pathways involved in venti lating the lungs (peripheral nerve and muscle d isorders), in some forms of l ung disease invol ving impaired gas diffusion (e.g. emphysema, asthma, bronchitis, pneumonia, lung cancer or aspiration), or due to pharmaceutical causes.

Metabol ic acidosis may result from inorgan ic acid addition, i.e. the in fusion or ingestion of HCI or NH4CI; or through gastrointestinal base loss through cond itions such as diarrhea, small bowel fistula/drainage, surgical d iversion, and renal tubular disorders; stimulation of chemoreceptors; lactic acid accum u lation; poison; or d iet. The Oi l^" solution of the present invention is effective in the treatment of acidosis regardless of cause.

Alkal inity increasing compositions of the invention typically comprise an amount of a base solution made from calci um hydroxide and/or calcium oxide or another elemental oxide or hydroxide, its solvates, hydrates, or combinations thereof, which is effective for the treatment or prevention of acidosis, as well as compl ications and related cond itions thereof in a mammal ian subject. A lkal ine water may be taken alone, or in a coordinate or combined formulation with one or more add itional agents to optim ize health and performance; prevent i llness;

decrease recovery times from exertion, i llness and injury; and extend endurance during exercise. Useful secondary or additional agents for use within the form ulations and methods of the present invention include, but are not l im ited to. alkal in ity increasing agents, adaptogens, am ino acids and amino acid derivatives, anti-inllammatory agents, anti-nausea agents, analgesics, antioxidants, aphrodisiacs, detoxifying agents, dietary supplements, herbal supplements, calming agents, herbs and plant extracts, flavorings, essential nutrients, coenzymes, electrolytes, energy boosters, essential trace elements, flavonoids, hormones, immune boosters, neurotransmitters, essential fatty acids, memory enhancers, vitam ins and m inerals, protein, sedatives, stim ulants and nutritional supplements for use w ithin the formulations and methods described herein.

With in these formulations and methods, the secondary agent may be provided in any of a variety of forms, including any polymorphs, enant iomers,

pharmaceutically acceptable salts, solvates, hvdrates, or combinations thereof. Typical ly, an alkalin ity increasing effective amount of an OH^" formulation wi l l comprise an amount of the active compound which is the rapeutical ly effective by itself or with one or more secondary agents, in a single or multiple un it dosage form, taken or applied over a specified period of therapeutic intervention, to measurably al leviate one or more symptoms of ac idosis or related conditions in the subject. Within exemplary embod iments, these compositions are effective within in vivo treatment methods to alleviate acidosis. The compositions described herein may additionally contain sweeteners, stabil izers, flavoring, anti- caking agents, flavor protectants, preservatives, fragrances, anti-lbam ing agents, colorants, emulsifiers and the like. The active compound may be optional ly formulated with a pharmaceutical ly acceptable carrier and/or various excipients, vehicles, stabi l izers, buffers, preservatives, fragrances, thickeners, etc.

In addition to generating C0_2- oxidative metabol ism may also cause oxidative stress. Oxidative stress is imposed on cel ls as a result of an increase in oxidant generation (includ ing reactive oxygen species), a decrease in antioxidant protection, or a failure to repair oxidative damage. It has been shown to lower intracellular pi I (Mulkey, 2004). It is bel ieved that intracel lular and extracel lular advanced glycation (AGEs) or l ipoxidation end products (ALEs), together with dysregulated glucose and l ipid metabolism, are important contributors to oxidant stress, enhanced cel luJar redox-sensitive transcription factor activity, and impaired innate immune defense, causing inappropriate inflammatory responses mediated in part by reactive oxygen species.

Oxygen has two unpaired electrons in separate orbitals in its outer shell.

Sequential reduction of molecular oxygen leads to the formation of a group of reactive oxygen species incl uding the superoxide anion, peroxide and hydroxyl radicals. Oxygen-deri ved radicals are generated constantly as part of normal aerobic li fe as oxygen is reduced along the electron transport chain in

m itochondria. Reactive oxygen species are also formed as necessary

intermediates in a variety of enzy me reactions.

However, these highly reactive radicals can also start a chain reaction w hich disrupts cel lular function. While they are a natural byproduct of metabolic function as wel l as part of phagocytosis, an excess of free radicals can occur for a variety of reasons. For example, an increase in the production of free radicals can be produced by drugs such as antibiotics that depend on qu inoid groups or bound W

metals for activity (n itrofurantoin), antineoplastic agents as bleomycin, anthracycl ines (adriamycin) and methotrexate. In addition, radicals derived from penici llam ine, phenylbutazone, some fenamic acids and the aminosal icylate component of sulphasalazinc are currently bel ieved to inactivate protease and 5 deplete ascorbic acid accelerating lipid peroxidation. Free radical production may also be increased by rad iati on, smoking, and inhalation of inorganic particles also known as mineral dust (e.g. asbestos, quartz, and si l ica) . Fever, excess glucocorticoid therapy and hyperthyroidism also increase the generation of oxygen-derived radicals due to increased metabolism. Furthermore, a wide0 variety of environmental agents including photochem ical air pol lutants such as pesticides, solvents, anesthetics, exhaust fumes and aromatic hydrocarbons can cause free radical damage to cells.

Free radical and ROS damage can be inhibited by antioxidants. An antioxidant i s a substance that when present in low concentrations relative to the oxidizable 5 substrate significantly delays or reduces oxidation of the substrate. Antioxidants protect the body by reacting with free radicals and other reactive oxygen species with in the body, h indering oxidation and reducing the amount of circulating free radicals. However, antioxidant supply is l im ited as an antioxidant molecule can only react with a single free rad ical. Therefore, there is a constant need to0 replen ish antioxidant resources, whether endogenously or through

supplementation. The compositions and methods of the present invention are effective as antioxidants for the el im ination and/or reduction of reactive oxygen species including free radicals, regardless of the source of the free radicals.

Antioxidant compositions of the invention typical ly com prise an amount of a base5 solution made from ca lcium hydroxide or ca lcium oxide, or other elemental oxides and hydroxides, its solvates, hydrates, or combinations thereof, which is effective for the treatment or prevention of excess free radicals as wel l as compl ications and rela ted conditions thereof in a mammal ian subject. Typical ly, an antioxidant effective amount (or free radical reducing effective amount) of an0 OH^" formulation of the present invention wil l comprise an amount of the active compound which is therapeutically effective, in a single or multiple unit dosage form, over a spec ified period of therapeutic intervention, to measurably alleviate one or more sym ptoms of free radical damage or related conditions in the subject. The active compound may be optionally form ulated with a pharmaceutical ly acceptable carrier and/or various excipients, vehicles, stabil izers, buffers, preservatives, etc.

The amount, tim ing and mode of delivery of compositions of the invention comprising an effective amount of a base sol ution either as an alkal in ity increasing agent, (antioxidant agent, free radical reducing agent) wi ll be routinely adj usted on an individual basis, depending on such factors as weight, age, gender, and condition of the individual, the severity of the acidosis and/or free radical damage or related symptoms, whether the administration is prophylactic or therapeutic, and on the basis of other factors known to effect drug delivery, absorption, pharmacokinetics, including, but not lim ited to, half-li fe, and efficacy. An effective dose or multi-dose treatment regimen for the instant alkalinity increasing or antioxidant formulations will ordinarily be selected to approximate a m inimal dosing regimen that is necessary and sufficient to substantia lly prevent or alleviate acidosis or excess free radicals and related cond itions in the subject. A dosage and adm inistration protocol wi l l often include repeated dosing therapy over a course of several days or even one or more weeks, months, or years. An effective treatment regime may also involve prophylactic dosage adm inistered on a day or multi-dose per day basis lasting over the course of days, weeks, months or even years.

An "effective amount," "therapeutic amount," "therapeutic e ffective amount." or "effective dose" is an amount or dose sufficient to el icit a desired pharmacological or therapeutic effect in a mammal ian subject: typically resulting in a measurable increase in alkalinity or reduction in free rad icals.

Therapeutic efficacy can alternatively be demonstrated by a measurement of blood gases, electron spin resonance, spin trapping, fingerprinti ng, measurement of free radical markers, liquid chromatography, measurement of markers of oxidative stress, or by altering the nature, recurrence, or duration of conditions associated with acidosis and/or excess free radicals includ ing, but not l imited to, Lesch- Nyhan syndrome, hemochromatosis, Alzheimer's disease, amyotrophic lateral sclerosis, atherosclerosis, cataracts, chronic obstructive pu lmonary disease, coronary artery disease, heart failure, hypertension, inflammatory bowel disease, macular degeneration, multiple sclerosis, Parkinson's disease, Reynaud 's phenomenon, reperfus ion inj ury, pancreatic impairment, methicill in-resistant Staphylococcus aureus (MR SA), hepatitis C, cellul itis, sepsis, foll iculitis, fibromyalgia, gout, arthritis, hypoxia and hypoperfusion, hemorrhage, ethanol toxicity, hepatic disease, diabetic ketoacidosis, exercise fatigue, systemic inflammatory response syndrome (SIRS), regional hypoperfusion, non-Hodgkin^* s and Burkitt's lymphoma, nausea, vomiting, hyperventilation, abdom inal pain, lethargy, shock, severe anem ia, hypotension, irregular heart rhythm, tachycardia, weight gain, cancer, cardiovascular disease, respiratory disease, infection, diabetes, cel lulitis and pancreatic impairment and infection. Therapeutic effectiveness may further be demonstrated by a reduction in the symptoms of skin conditions such as psoriasis. MRSA, Morgellons disease and fungal in fections such as candidiasis, ti nea cruris, and tinea pedis. Therapeutic effectiveness may add itional ly be demonstrated by a reduction in the number of secondary in fections experienced by a subj ect, particularly in a subject with a comprom ised immune system .

Therapeutic effectiveness may further be demonstrated by a decrease in the symptoms of the conditions being treated, for instance, a decrease in acidem ia. hyperlactem ia. lactic acidosis, lactic ac id bu ild up, abscesses, boi ls, redness, pai n, headache, a general sick feeling, muscle aches, shortness of breath, tatigue, fever, shivering and chest pain of m i ld to medium intensity, muscle aches, joint pain, bone pain, chest pain, painful breathing, shortness of breath, fever and chi lls, low blood pressure, fatigue, headaches, rash, malaise, septic shock, septic arthritis, abscesses deep with in the body, blood poisoning, or septicemia, a bone infection called osteomyel itis, meningitis, endocarditis, pneumonia, joint inflammation, confusion, lethargy, rapid breathing, shortness of breath, wheezing, chest pain or pressure, joint stiffness, swel l ing, joint deformity, crepitus, non-spec i fic fever, joint inflammation, headaches, fatigue, a fee ling of euphoria,

nausea, seizures, com a, general ized weakness, abnormal heart function, decreased platelet count, areas of mottled skin, fever, low blood pressure, tachycardia, skin discoloration, irregular heartbeat, loss of appetite, jaundice, abdom inal pain, memory loss, mood swings, musculoskeleta l pain, easy bruising, nausea, vom iting, ascites, easy bruising, dry skin, dry mouth, low blood pressure, frequent urination, chest pain, lymph node pain, night sweats, ski n rash, hyperventilation, constipation, severe anemia, and light headedness.

Therapeutic effectiveness may also be demonstrated by a decrease in the amount of other pharmaceutical agents necessary to treat a disease, or an increase in the effectiveness of current dosages. For example, the compositions of the present invention may increase the effectiveness of chemotherapeutic agents, decreasing the amount of chemotherapeutic agents needed or the length of the treatment needed.

Therapeutic effectiveness may be determ ined, for example, through an arterial blood gas. I n an arterial blood gas test, arterial blood is taken from any easi ly accessible artery (typical ly either radial, brachial, or femoral) or out of an arterial l ine. Once the sample is obtained, care should be taken to elim inate visible gas bubbles, as these bubbles can dissolve into the sample and cause inaccurate results. The sealed syringe is then taken to a blood gas monitor. The mach i ne aspirates the blood from the syringe and measures the pH and the partial pressures of oxygen and carbon dioxide and the bicarbonate concentration, as wel l as the oxygen saturation of hemoglobin. Normal pH of blood is between about 7.4 and 7.3, preferably 7.365. Effective amounts of the mixtures of the present invention wi l l increase plasma pi 1 from below 7.0 to a pi I of about 7.6 to 7.3. Effective alkal inity increasing amounts may increase plasma pH of 6.0 to a pH of about 6.5, preferably to about 6.7, more preferably to about pH 7.0, preferably to a pH of 7.4 or higher. Effective alkal inity increasing amounts may increase plasma pH of 6.0 to a pH of about 6.5, preferably to about 6.7, more preferably to about pH 7.0. preferably to a pH of 7.4 or higher.

Therapeutic effectiveness may also be demonstrated through a l itmus test in which a sample of sal iva is taken upon awakening and tested with a strip of l itmus paper. A urine sample may also be tested with a strip of l itmus paper or a l itm us test strip. The litmus paper is then compared to a l itmus scale to determ ine the pi I of the sample. Optimal ly, the pH of sal iva is about 7.4 and the pi I of urine is about

6.6. The methods and compositions of the present invention are therapeutical ly effective to increase the pH of saliva and/or urine by about 2-40%, 5- 1 5%, 10- 20% or more.

Therapeutic effectiveness may additionally be determ ined using a Lactic acid meter. During intense exercise, physiological pi I levels increase indicating an increase in ac id in the body. The effect of alkal ine water on lowering elevated physiological pH can be determ ined using a lactic acid meter. Measurements may be taken before, during, and after intense activity. An effective amount of an Alkaline water composition would maintain normal or decrease elevated levels of physiological pH during exercise. In some embodiments, alkal ine water consumed during exercise wi ll decrease the drop in physiological pH. In other embodiments, Alkal ine water consumed during exercise wi ll prevent a drop in physiological pH. In additional embodiments, alkal ine water consumed after exercise wil l increase the rate at which physiological pH returns to baseline levels.

In some embodiments, the consumption of A lkaline water as described herein during exercise wi l l increase an individual's maximal lactate steady state allowi ng them to exerc ise longer and harder than had previously been possible.

Therapeutic effectiveness as a free radical scavenger may further be demonstrated through electron spin resonance. Electron spin resonance (ES ) is a spectroscopic technique which detects species that have unpaired electrons such as free radicals. The degeneracy of the electron spin states characterized by the quantum number, iris = ± 1 /2, is l ifted by the appl ication of a magnetic field and transitions between the spin levels are induced by radiation of the appropriate frequency. An un- paired electron interacts with its environment, and the detai ls of ESR spectra depend on the nature of those interactions. The integrated intensity of the spectrum is proportional to the concentration of radicals in the sample. An effective free radical reducing or antioxidant amount of the m ixture of the present invention wi ll decrease the intensity of the spectrum by 2-50%, 1 0-40%, 1 5-30%, 20-25% or more.

Spin trapping provides a nitrone or nitrose compound for an addition reaction which produces an electron spin resonance spectroscopy-detectable am inoxyl rad ical. The product of the reaction can then be measured through electronic resonance spectroscopy . Effectiveness of the compositions of the present invention as a free radical scavenger may be demonstrated by a decrease in the product of the reaction by 2-50%, 10-40%, 1 5-30%, 20-25% or more.

Oxidative stress as a result of free radical production can be measured in myriad ways including, microplate cold light cytotluorimetry, and measurement of coili ng of D A, and cytochrome C production. Oxidative stress caused by free radicals may also be determined through measurement of thiobarbi turic acid reacting substances, measurement of pentane and ethane, measurement of creatine kinase, and measurement of conjugated dienes. Effective free radical reducing or antioxidant amounts of the composition of the present invention will reduce the amount of the measured markers by 2-50%, 10-40%, 1 5-30%, 20-25% or more. In microplate cold light cytofluroimetry, permeable probes are inserted directly in l iving cel ls using a method of UV and visible fluorescent detection. Some particles are known to have fluorescence (such as cigarette smoke particles) when they react with free radicals and the amount of free radical damage can be assessed by the amount of fluorescence in a sample. A quantitative measure can be obtained using a flow cytometer. This method also eva luates intracel lular glutathione and hydrogen peroxide production. A free rad ical reducing effective amount of a m ixture of the present invention wi l l decrease the fluorescence by 2- 50%, 1 0-40%, 1 5-30%, 20-25% or more.

Therapeutic effectiveness of the solution as a free radical scavenger may further be demonstrated by the measurement of the proportion a relaxed coi l DNA to that of supercoiled DNA wherein X = Relaxed coil DNA / Supercoi led DNA. Plasm id DNA is incubated with 5 μΙ of particle suspensions at 37°C in a water bath. The supercoi led, relaxed coi led and linearised plasm id DNA are separated by electrophoresis and quantified by scanning. The h igher the value of X, the more oxidative damage (based on free radicals damaging the supercoi led DNA and causing it to uncoi l). An effective free radical reducing or antioxidant amount of a m ixture of the present invention wi ll decrease the value of X by 2-50%, 1 0-40%. 1 5-30%, 20-25% or more.

The rate of Cytochrome C reduction can be measured using lum inol induced chemi lum inescence for quantifying the results. Therapeutical ly effective free radical reducing or antioxidant amounts of the solution of the present invention wil l decrease the rate of cytochrome C reduction by 2-50%, 1 0-40%, 1 5-30%, 20- 25% or more.

Therapeutic effectiveness may be demonstrated by a decrease or absence of an infection. For example, M RSA may be detected by cu lture, blood test, skin culture from the infected site, culture of the drainage from the i nfection, urine culture, and sputum culture. An effective treatment with the 01 composition according to the form ulations and methods of the invent ion wi l l decrease M RSA levels by 5%, 1 0%, 20%, 30%, 50% or greater reduction, up to a 75-90%, or 95% or greater, reduction.

Following adm inistration of the OFF composition accord ing to the formulations and methods of the invention, test subjects will exhibit a 5%, 1 0%, 20%, 30%, 50% or greater reduction, up to a 75-90%, or 95% or greater, reduction, in one or more symptoms assoc iated with acidosis or excessive free radical production as compared to placebo-treated or other suitable control subjects. Test subjects may also exhibit a 1 0%. 20%, 30%. 50% or greater reduction, up to a 75-90%. or 95% or greater, reduction, in the symptoms of one or more conditions assoc iated with acidosis or excessive free radical production including, but not l im ited to, gout, abdom inal pain, A lzheimer's disease, amyotrophic lateral sclerosis, tlbromyalgia, fungal infections including but not lim ited to candidiasis, arthritis, atherosclerosis, cancer, card iovascular disease, cataracts, cel lulitis and pancreatic impairment, chronic obstructive pulmonary disease, coronary artery disease, diabetes, d iabetic ketoacidosis, ethanol toxicity, exercise fatigue, fol liculitis, gout, heart failure, hemochromatosis, hemorrhage, hepatic disease, hepatitis C , hypertension, hyperventi lation, hypotension, hypoxia and hypoperfusion, infection,

inflammatory bowel disease, irregular heart rhythm, Lesch-Nyhan syndrome, lethargy, macular degeneration, methici llin resistant staphylococcus aureus ( RSA), orgel lons disease, mu ltiple sclerosis, nausea, non-Hodgk in^*s and

Burkitf s lymphoma, Parkinson's d isease, psoriasis, regional hypoperfusion, reperfusion inj ury, respiratory disease, system ic inflammatory response syndrome (S I RS). Reynaud^'s phenomenon, sepsis, severe anemia, shock, tachycard ia, tinea cruris, vomiting and weight gain.

The pharmaceutical compositions of the present invention may be adm inistered by any means that achieves the intended therapeutic or prophylactic purpose.

Suitable routes of admin istration for alkal izing and antioxidant compositions of the i nvention compris ing 01 Γ sol utions include, but are not l im ited to. oral, buccal, nasal, aerosol., mucosal, injectable, slow release, controlled release, iontophoresis, sonophoresis, and other conventional delivery routes, devices and methods. Injectable delivery methods are also contemplated, includ ing but not l im ited to. intravenous, intramuscular, intraperitoneal, intraspinal, intrathecal, intracerebroventricular, intraarterial, and subcutaneous i njection.

With in add itional aspects of the invention, combinatorial formu lations and coord inate adm inistration methods are provided which employ an effective amount of Oil^" compositions, and one or more additional active agent(s) that is/are combinatorial ly form ulated or coordinately adm inistered with the OH^" solution— yielding an effective formulation or method to modulate, al leviate, treat or prevent acidosis or excessive free radicals in a mammal ian subject. Exemplary combinatorial formulations and coordinate treatment methods in this context employ a base solution in combination with one or more additional or adj unctive therapeutic agents.

Such secondary or additional agents for use within the formulations and methods of the present invention include, but are not l imited to, alkal inity increasing agents, adaptogens, am ino acids and amino acid derivati ves, anti-inflammatory agents, anti-nausea ag,ents, analgesics, antioxidants, aphrodisiacs, detoxi fying agents, dietary supplements, herbal supplements, calm ing agents, herbs and plant extracts, flavorings, essential nutrients, coenzymes, electrolytes, energy boosters, essential trace elements, llavonoids, hormones, immune boosters,

neurotransmitters, essential fatty acids, memory enhancers, vitam ins and m inerals, protein, sedatives, stimu lants and nutritional supplements for use within the formulations and methods described herein. Within these formulations and methods, the seconda ry agent may be provided in any of a variety of forms.

includ ing any polymorphs, enantiomers, pharmaceutically acceptable salts, solvates, hydrates, or combinations thereof. Such combi nations of an 01 composition and secondary agent may be administered either combinatorial ly or coord inately as d isclosed herein to effective ly optim ize health and performance; prevent illness; decrease recovery times from exertion, i llness, and inj ury; increase energy levels; im prove exercise performance; im prove hydration; prevent musc le damage after exercise; and increase stam ina duri ng exerc i se.

Such additional or adj unctive therapeutic agents may be add itional alkal inity i ncreasing agents i ncluding, but not l im ited to sodium bicarbonate; a carbonate, a phosphate, or a hydroxide of sodium or potassium; magnesium carbonate;

magnesium hy droxide; ammonium carbonate; ammonium bicarbonate;

magnesium oxide; sodium or potassium citrate, bicarbonate, sulfate, and bcnzoate; ascorbate; calcium carbonate; or any pharmaceutically acceptable material that causes the pH of an aqueous med ium to rise above pH 7.0. or m ixtures thereof. Additional or adj unctive therapeutic agents may also include antioxidants including, but not l im ited to, xanthine oxidase inhibitors, including, but not l im ited to. allopurinol and folic acid; NADPH oxidase inh ibitors, including, but not limited to, adenosine; calcium channel blockers; superoxide dismutases;

catalases; album in; inhibitors of iron redox cycling, including, but not lim ited to deferoxamine, apotransferin and ceruloplasm in; beta carotene; ascorbates; myricetin-3-O-galactoside, quercitin-3-O-gal actoside; alpha tocopherol; and benzaldehyde derivatives, such as those described in U.S. Patent Appl ication No. 1 2/4 1 8,342, incorporated by reference herein in its entirety. Further additional or adjunctive therapeutic agents may include but are not lim ited to, probenecid. allopurinol, nonsteroidal anti-inflammatory drugs (NSAl Ds). colchicine, corticosteroids, uricosuric agents, xanthine oxidase inhibitors, losartan, fenofibrate, urate oxidase, Y-700, COX-2 inh ibitors, analgesics, corticosteroids, disease-modi fying anti-rheumatic drugs, antibiotics, vasodepressors, sulfasalazine, radiation therapy, chemotherapy, duloxetin, milnacipran, gabapentin. pregabal in, and benzaldehyde derivatives such as those described in U .S. Patent Appl ication

No. 12/4 1 8,342, incorporated herein by reference in its entirety.

Adaptogen agents for use with in the formulations and methods herein include, but are not l im ited to, ashwagandha, eleutherococcus senticosus, reishi, astragalus, l icorice root, panax quinqucfolius, panax ginseng and sc hisandra berries.

Antioxidants included in the formu lations provided here in may be in the form o f nutritional supplements such as, but not limited to, vitamin Λ; vitam in C; vitam in B; erythorbic ac id; beta-carotene; carotenes: lutein; manganese; lycopene;

melatonin; or coenzyme Q 1 0; xanthine oxidase inh ibitors, including, but not l im ited to, al lopurinol and fol ic acid; NADP1 1 oxidase inh ibitors, including, but not limited to, adenosine; calcium channel blockers; superoxide dismutases;

catalases; album in; inh ibitors of iron redox cycling, includ ing, but not limited to de feroxamine, apotransferin and ceruloplasm in: beta carotene; ascorbates;

myricetin-3-O-galactoside, qiiercitin-3-O-gaiactoside; alpha tocopherol; and benzaldehyde derivatives, such as those described in U . S. Patent Application No. 1 2/4 1 8,342, incorporated by reference herein in its entirety. In some

embodiments, antioxidants may be present in plant extracts wh ich may also be combined with the alkaline water. Plant extracts may come from plant sources such as, but not l imited to, apricot, acai fruit, acerola, apple, blueberry, blac kberry, black currant, carrots, cherry, chokeberry, c ranberry, elderberry, green tea, goj i berry, grape seed, mangosteen, maqui berry, m ilk thistle, pomegranate seed, prune, raspberry, red grape, rooibos, rosehips, strawberry, seabuckthorn, white grape, whole grape, yumberry and acerola fruit.

Vitamin, m ineral and nutritional supplements for use here in may be in a variety of forms including, but not lim ited to, vitam in B complex, fol ic acid, niacin, niacinamide, pantothenic acid, pyridoxine HC I, v itam in B2, folate, biotin, vitam in C, vitam in D, vitamin D₃, vitamin E, vitam in . cyanocobalam in. inositol, thiam ine, thiamine mononitrate, calcium pantothenate, mixed tocophyerols, d- alpha tocopheryl acetate, magnesium, calcium, calcium carbonate, calcium chelate, calc ium di-phosphate, calcium phosphate, iron, magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, manganese chelate, manganese sulfate, potassium, potassium chelate, potassium chloride, sod ium, zinc, vanadyl sulphate, chrom ium, chrom ium chloride, chrom ium picolinate. and chrom ium polyn icotinate.

Amino acids, am ino acid precursors and der ivatives as used with in the formulations herein may be branched or straight cha in amino acids. Exemplary am ino acids, precursors and derivatives which may be used in the formulations and methods described herein include, but arc not l im ited to. 5-1 ITP, arginine, beta alanine, carnitine fumarate, citrulline inalate, glutam ine peptide, glyc ine, I- alanine, 1-arginine. l-arginine hydrochloride, l-histidine, 1-meth ionine, l-lysine

1 1C1, l-phenylalani ne, leucine ethyl ester, 1-g lutam ine. l-isoleucine, 1-theanine, 1- tyrosine, phenylalanine, taurine, tri-methyl glycine, tryptophan, tyrosine, I- camitine, l-carnosine, glutam ine alpha ketoglutarate and alpha-L-polylactate. Electrolytes used with the formulations herein include, but are not limited to, sod ium chloride, sodi um acetate, acidic sodi um citrate, ac idic sodium phosphate, sodium chloride, sodi um bi carbonate, sodium brom ide, sodium citrate, sodium lactate, sodium molybdate, sodium phosphate, anhydrous sodium sulphate, sodium su lphate, sodium tartrate, sodium benzoate. sodium selenite, and other sodium salts and mixtures thereof; potassium chloride, potassium acetate, potassium bicarbonate, potassium bromide, potassium citrate, potass ium-D- gluconate, monobasic potassium phosphate, potassium tartrate, potassium sorbate, potassium iod ide, and other potassium salts and m ixtures thereof; magnesium carbonate, magnesium citrate, magnesium oxide, magnesi um phosphate, as wel l as other magnesium salts and mixtures thereof; calcium chloride, calcium carbonate, calcium chelate, calcium di-phosphate, calcium lactate, calcium phosphate tribasic and other calcium salts and mixtures thereof. Such electrolytes may be included in the formulations described herein in proportions and amounts suitable to replen ish salts lost during exercise or illness or otherwise depleted. Anti-inflammatory agents for use within the formulations and methods herein include, but are not limited to, extracts from plants such as maqui berry, milk thistle, skul l cap, red raspberry, red sour cherry, green tea and hops.

Other agents which may be used in the compositions and methods described herein include anti-nausea agents including, but not lim ited to, extracts from pepperm int, ginger and chamom ile.

A further agent which may be used in the compositions and methods described herein includes analgesic agents such as, but not lim ited to, white wi llow bark. The form ulations and methods described herein may additional ly include herbal supplements and extracts with beneficial properties including, but not l im ited to, passion flower, horny goat weed, skullcap, m i lk thistle, Echinacea, dandelion leaf, St. John's wort, green tea, black tea, chamomile or peppermint, or an extract thereof.

The formulations and methods described herein may further include plants with beneficial properties includ ing, but not lim ited to, guarana seeds, acerola berries, coconut water, yerba mate, acai berry, ginseng root, panax ginseng root, ginkgo bi loba, white w il low bark, acacia, ashwagandha, chokeberry, elderberry, cranberry, maqu i berry, blueberry, pomegranate, rooibos, goj i berry, elder berry , valerian, seabuckthom, yumberry, blackberry, astragalus, damiana, and ginger. Energy boosters that may increase performance and are contemplated for use within the methods and formulations described herein include, but are not limited to, creatine ethy l ester, creatine monohydrate, magnesium creatine chelate, creatine hydrochloride, creatine n itrate, creat ine monohydrate and royal jel ly. Useful ilavonoids within the compositions and methods of the present invention are present in chamom ile extract, cocoa powder, red grape, black tea, and white tea, ginkgo biloba, berries, parsley, and green tea some or al l of wh ich may be included in the compositions and methods described herei n.

Useful sedatives for use within the compositions and methods described herein include, but are not lim ited to, lavender, lemon balm, lernongrass, linden, oatstraw, St. John' s wart, valerian root, kava kava, hops and passion flower.

Stimulants for use within the methods and compositions described herein include, but are not lim ited to, caffeine, citicoline, d-glucuronolactonc, guarana extract, ginseng, concentrated green tea, green coffee beans, glucuronolactone, guarana, panax ginseng, panax quinquefolius, Siberian ginseng, and theobrom ine. Additional agents which may be included in the formulations and methods described herein are immune boosters including, but not lim ited to, Echinacea and astragalus root.

Flavoring agents for use with the compositions and methods described herein include, but are not l im ited to fruit juice, vegetable j u ice, mi lk sol ids, fruit flavors, herbal flavor and mixtures thereof. The fruit ju ice can be any citrus j uice, non- c itrus j uice, or mixture thereof, which is known for use in di lute j uice beverages. The j uice can be derived from, but not lim ited to. apple, cranberry, pear, peach, pl um, apricot, nectarine, grape, guava, cherry, currant, raspberry, gooseberry. elderberry, blackberry, blueberry, strawberry , lemon, l ime, mandarin, orange, tomato, lettuce, dandelion, rhubarb, pineapple, coconut, pomegranate, kiwi, mango, papaya, banana, watermelon, passion fruit, tangeri ne, and cantaloupe. The vegetable juice can be any vegetable ju ice general ly consumed i ncluding but not lim ited to, celery, spinach, cabbage, watercress, carrot, beet, spirul ina, sweet potato, kale, romaine, col lard greens, endive, escarolc, bok choy, fennel, parsley, wheat grass, or cucumber. Such fruit and vegetable j uices may or may not have additional beneficial properties such as antioxidants and/or llavonoids.

Formulations and met hods herein may additional ly include a protein source. Protein sources include, but are not limited to, mi lk sol ids, calcium caseinate, whey protein concentrate, whey protein isolate, whey protein hydrolysate, soy protein, casein hydrolysate, rice protein, wheat protein, corn protein, partial ly hydrolyzed whey protein, or ultra-filtered w hey protein.

Formulations and methods herein may further include one or more sweeteners or other carbohydrate source. Such sweeteners include, bu t are not l imited to, acesulfame potassium, aspartame, cane sugar, corn syrup, c rystalline fructose, dextrose, D-ribose, fructose, glucose, glucose-fructose syrup, high fructose corn syrup, high fructose l i quid sugar, honey, mal todextrin, sorbitol, stevia, sucralose, sucrose, sugar, trehalose, truvia or xylitol.

The use of these additional or adj unctive therapeutic agents in conj unction with the alkalizing or antioxidant agent of the present invention may increase the effectiveness of the therapeutic agents and/or decrease the amount of such agents that may be required.

In some embodiments, the alkal inity increasing agent may be administered in conj unction with an additional therapeutic agent to facilitate consumption of the additional therapeutic agent. For example, some therapeutic agents may be extremely acid ic. Such agents may be administered in conj unction with the alkal in ity increasing agent to neutralize the acidity and increase the forms of adm in istration that would be acceptable. In another embodiment, the alkal in ity increasing agent may be used to temporari ly neutral ize stomach acid or other acid conditions so that therapeutic agents which are destroyed by acid such as, but not l im ited to, nutritional supplements or other organics such as vitamins, i ncluding vitam in B |₂, can be ingested.

In certain embodiments, the invention provides combinatorial alkalizing or antioxidant formulations comprising a base solution made from calc ium hydroxide and/or calcium oxide and one or more adj unctive agent(s) having alkal izing or antioxidant activity, or both, or add itional adj unctive agents wh ich may have neither alkal izing nor antioxidant activity but which are usefu l in the treatment of underlying conditions or prophylactical ly. Within such combinatorial formu lations, the OH solution and the adj unctive agent(s) having alkalizing and/or antioxidant act ivity, or non-alkal izing/antioxidant agents wi l l be present in a combined formulation in effective amounts, alone or in combination. In exemplary embodiments, a base solution and a non-calcium hydroxide based alkal izing and/or antioxidant agent will each be present in an alkal izing and/or antioxidant amount (i .e., in singular dosage which wi l l alone el icit a detectable alkalizing or free radical reduced response in the subject). Alternatively, the combinatorial formulation may comprise one or both of the OH^" solution and a non-calcium hydroxide based alkalizing and/or antioxidant agent or other adj unctive agent in sub-therapeutic singular dosage amount(s). wherein the combinatorial formulation comprising both agents features a combined dosage of both agents that is col lectively effective. Effectiveness may elicit an alkalizing or free radical reducing response or other increased therapeutic response. Thus, one or both of the OH^" solution and a non-calcium hydroxide based alkal izing and/or antioxidant agents may be present in the formulation, or administered in a coordinate adm inistration protocol, at a sub-therapeutic dose, but collectively in the formulation or method they el icit a detectable alkal izing and/or antioxidant response in the subject.

To practice the coordi nate adm inistration methods of the invention, an OH^" m ixture is adm in istered, simultaneously or sequentially, in a coordinate treatment protocol with one or more of the secondary or adj unctive therapeutic agents contemplated herein. The coord inate administration may be done simultaneously or sequential ly in either order, and there may be a time period wh i le only one or both (or all) active therapeutic agents, individual ly and/or col lectively, exert their biological activities. A distinguishing aspect of all such coordinate treatment methods is that the 01 Γ solution exerts at least some detectable alkal izing or antioxidant activity, and/or el icits a favorable cl inical response, which may or may not be in conj unction with a secondary cl inical response provided by the secondary therapeutic agent. Often the coordinate adm ini stration of a base solution with a secondary therapeutic agent as contemplated herein w i l l y ield an enhanced therapeutic response beyond the therapeutic response elicited by either or both the OH^" solution and/or secondary therapeutic agent alone.

The amount, tim ing and mode of delivery of compositions of the invention comprising an effective amount of a base solution of the present invention wi l l be routinely adj usted on an individual basis, depending on such factors as weight, age, gender, and condition of the individual, the severity of the acidosis, ROS levels includ ing free radical production or related symptoms, whether the adm inistration is prophylactic or therapeutic, and on the basis of other factors known to effect drug delivery, absorption, pharmacokinetics, includ ing, but not l im ited to, half-life, and efficacy .

Effective doses may be extrapolated from dose-response curves deri ved from in vitro or animal model test systems. Such ani mal models and systems are wel l known in the art. The precise dose to be employed wi l l also depend on the route of adm inistration, the seriousness of the disease or disorder, and body size, and should be decided according to the judgment of the practit ioner and each patient's circumstances. However, suitable dosage ranges for oral adm inistration are general ly about 5 ounces (0. 147L) to about 1 35.256 ounces (4 L) of the di luted OH^" solution (having a pH between 7.5 and 9.5) per day. In specific preferred embodiments of the invention, the oral dose is about 5 ounces (0. 147L) to about 1 00 ounces (2.9L), about 5 ounces (0. 147L) to about 90 ounces (2.6 L) of OH^" solution per day, more preferably about 8 ounces (.236 L) to about 80 ounces (2.36 L) of OH^" solution per day, more preferably about 24 ounces (0.7L) to about 32 ounces (.94L) per day, more preferably about 32 ounces (.94L) to about 48 ounces ( 1 .4L) per day, more preferably about 35 ounces ( 1 .035 L) to about 80 (2.36L) ounces per day. In some embodiments, the OH^" solution is adm inistered over the course of a day, for example the dosage is taken over eight hours, ten hours, twelve hours or 24 hours. In some embodiments, the dose may be calibrated based on body size, with effective doses comprising between about 0.0 1 to about 5 oz/pound, 0.3 to about 5 oz/pound, about 0.3 to about 3 oz/pound, about 0.3 to about 1 oz/pound, about 0.35 oz/pound. For examp le, an individual weigh ing 225 lbs would be given a starting dose of about 80 ounces (2.36E ) of d i luted OH^" sol ution, as described in Example X I ; an individual weighing 1 80 pounds would receive a starting dose of 64 oz ( 1 ,9L) of the solution of Example XI per day. An individual weighing 1 35 pounds would receive a starting dose of 48 oz ( 1 .4L) of the solution of Example X I per day. An individual weigh ing 90 pounds would be given a starting dose of 32 oz (0.94 L) of the solution of Example X I per day. An individual weighing 45 pounds would be given a starting dose of 1 6 oz (0.47E) of the solution of Example X I per day and an individual weigh ing 22 lbs would be given a starting dose of 8 oz (0.236E) of the solution of Example X I per day. In other embodiments, fractions of the dosage are administered at particular time points, for example every hour, every two hours, every three hours, every four hours, eve ry eight hours, every twelve hours, or any other fraction of time, as tolerated by the patient. For example, 0.5 E may be adm inistered every hour, every two hours, every three hours, every four hours, every eight hours, every twelve hours, or any other fraction of time as tolerated by the patient. In one embodiment, one ounce of alkalizing material could be m ixed in 1 liter of w ater. In another em bodiment, three ounces of alkal izing material would be m ixed in two liters of water. In a further embodiment, once the desired physiological pH level is obtained, a maintenance dose may be taken indefin itely. In some embodiments, a maintenance dose may be ½ of the therapeutic level, 1 /3 of the therapeutic level, ¼ of the therapeutic level, or any other reduced dosage as determ ined by the judgment of the practitioner and the patient^' s circumstances. The formulations may be presented in unit -dose or multi-dose containers.

Preferred unit dosage formu lations are those containing a daily dose or uni t, dai ly sub-dose, as described herein above, or an appropriate fraction thereof, of the active ingredient(s). In one embodiment eight ounces of the prepared formulation is administered every four hours. In another embodiment, eight ounces of the prepared formulation is administered every three hours. In a further embod iment, 0.5 L is adm inistered every four hours. In another embodiment, 0.5 L is adm inistered every eight hours. In stil l another embodiment, eight ounces of the prepared formulation is adm inistered every two hours or fraction thereof. I n exemplary embodime nts, unit dose formulations are in 0.5 L, or a multiple thereof. In other embodiments, fractions of the dosage are adm inistered at particular time points, for example every hour, every two hours, every three hours, every tour hours, every eight hours, every twelve hours, or any other fraction of time, as tolerated by the patient. In one embodiment, one ounce o f anti-oxidant material could be m ixed in 1 liter of water. I n another embodiment, three ounces of antioxidant materia l wou ld be m ixed in two l iters of water. In a further embodiment, once the desired physiological pi I level is obtained, a maintenance dose may be taken indefin itely. In some embodiments, a maintenance dose may be ½ o f the therapeutic level, 1 /3 of the therapeutic level, ¼ of the therapeutic level, or any other reduced dosage as determined by the j udgment of the practitioner and the patient's circumstances.

The formulations described herein may be manufactured and sold in a variety of forms. In some embodiments, they may be manufactured and sold as a single strength beverage for direct consumption by the consumer. In other embodiments, the formulations may be sold in an aqueous concentrate to be diluted w ith water to yield a beverage that treats or prevents acidosis, symptoms of ac idosis, and conditions caused by or exacerbated by acidosis. Formulations may include excipients recognized in the art of pharmaceutical compounding incl ud ing, but not l im ited to, binders, fil lers, lubricants, emulsifiers, suspending agents, sweeteners, flavorings, preservati ves, buffers, and other conventional excipients and additives. These additional formulation additives and agents will often be biological ly inactive and can be adm inistered to patients without causing deleterious side effects or interactions with the active agent.

The formulations may also be sold as a gel, powder, granule formation, or tablet which is to be dissolved in water to yield a beverage that treats or prevents acidosis, symptoms of acidosis, and conditions caused or exacerbated by acidosis. In some embodiments, the compositions described herein are formulated for topical adm inistration. Such topical administration may take the form of gels, lotions, mi lks, creams, water-in-oil or oi l-in-water emulsions, sprays, suspensions, hair care products, and emol l ients. Such topical forms may include thickeners, stabi lizers or gell ing agents made from any suitable polysaccharide including, but not limited to, xanthan gum, carrageen, algi nate, alginic acid, pectin, hyaluronic acid, chondroitin sulfate, selerorium, gum Arabic, gum karaya. gum tragacanth. carboxymethyl-chilin, cel lu lose gum, ch itosan, cation ic guar gum.

hydroxyethylcellulose, starch, dextrins, guar gum. cellulose ethers,

carboxymethylchitosan, N-hydroxy-dicarboxyethyl-chitosan, modified potato starch, cetyl hydroxyethylcel lulose or polyquatern ium. In some embod iments, the thickener may be an anionic polysaccharide, cationic polysaccharide, nonionic polysaccharide, amphoteric polysaccharide or hydrophobic polysaccharide.

I n some embodi ments, a suitable topical form such as a gel may com prise 1 % to 1 0% xanthan gum or ot her thickening agent, preferably about 1 % to about 5%, about 1 % to about 3%, about 1 % to about 2.9 %, about 2.89% of the th ickening agent by weight.

In some embod iments, the th ickened alkaline water composition may additional ly comprise a preservative such as preservative is ethyl alcohol, methyl alcohol, polyvinyl alcohol, and isopiropyl alcohol. The preservati ve may comprise from about 1 % to about 10%, about 2 % to about 8%. about 3 to about 5%, about 2% to about 4%, about 3.785%, preservative such as, but not l im ited to, isopropyl alcohol by weight.

The thickened alkal ine water composition is compatible w ith any type of emollient, preservative, pigment, vitamins, emulsi fiers, ultraviolet fi lters and sunscreens, surfactants, preservatives, fragrance, humectants, glycols, oils, waxes, sil icones, antioxidants or other agents general ly used in formulations developed for topical appl ication to the skin, hair or nails. I n some embodiments, add itional antioxidants may be added to the composition.

Any suitable emu lsifier known in the art for use in water-in-oi l or oi l-in water or microemulsions may be used alone or in combination in the formulations described herein. Exemplary emulsifiers include, but are not l imited to sesqiiioleates, ethoxylated esters of derivatives of natural oils, si licone emulsifiers, anionic emulsifiers, ethoxylated fatty alcohols, ethoxylated sorbitan esters, ethoxylated fatty acid esters, ethoxylated stearates, glyceryl monostearates.

sorbitan esters, ethoxylated monoglycerides, ethoxylated diglyccrides, ethoxylated triglycerides, methylglucose esters, polyacry lamide emulsifiers, polymeric emiilsifiers, cationic emulsi fiers, or mixtures thereof.

Any suitable emol l ient known to those of ski l l in the art may be used with the formulations and methods described herein. Exemplary emol l ients include, but are not lim ited to, hydrocarbon oi ls such as paraffin or mineral oils; waxes such as beeswax or paraffin wax; natural oils such as sunflower oi l, apricot kernel oil, shea butter, or jojoba oil; si licone oils such as dimethicone, cyclomethicone or cetyldimethicone; fatty acid esters including, but not lim ited to, isopropyl palmitate, isopropyl myristate, dioctyhnaleale, glyceryl oleate and cetostearyl isononanoate; fatty alcohols including, but not l imited to, cetyl alcohol, or stearyl alcohol; polypropylene glycols; or polyethylene glycol ethers; and m ixtures thereof.

Topical formulations as described herein may additionally include humectants or moisturizers including, but not lim ited to, polyols, exothylated glycerin, polyethylene glycols, propylene glycol, si licone glycol, xyl itol, urea, honey, hydrogenated honey, hydrogenated starch hydrolystaes, glycerin, sorbitol, hydroxyethyl urea, 1 , 3-butylene glycol, aloe vera, and propylene glycol.

The gel formulations as described herein may be spread d irectly on mammalian skin or be appl ied to or part of a flexible support or pad wh ich can then be appl ied to mammal ian skin.

Additional OH solutions of the invention can be prepared and adm in istered in any of a variety of inhalation or nasal delivery forms known in the art. Devices capable of depositing aerosolized OH^" formulations in the sinus cavity or pulmonary alveol i of a patient include metered dose inhalers, nebul izers, sprayers, and the l ike. Methods and compositions suitable for pu lmonary delivery of drugs for systemic effect are wel l known in the art. Suitable formulations, wherein the carrier is a l iquid, for adm inistration, as for example, a nasal spray or as nasal drops, may include aqueous or oily solutions of calcium hydroxide or calci m oxide and any additional active or inactive ingredient(s).

Yet additional OH^" formulations are provided for parenteral administration, including aqueous and non-aqueous sterile injection solutions which may optional ly contain antioxidants, buffers, bacteriostats and/or solutes which render the formulation isotonic with the blood of the mammal ian subject; and aqueous and non-aqueous sterile suspensions which may include suspending agents and/or thickening agents.

In more detai led embodiments, OH^" compositions may be encapsulated for del ivery in m icrocapsules, rnicroparticles, or m icrospheres, prepared, for example, by coaccrvation techniques or by interfacial polymerization, in colloidal drug delivery systems (for example, l iposomes, al bumin m icrospheres,

m icroemulsions, nano-particles and nanocapsules) or in macrocmulsions.

In further embodiments, the pharmaceutical agents of the invention may be adm inistered parenteral ly, e.g. intravenously, intramuscu larly, subcutaneously or intraperitoneally. The parenteral preparations may be sol utions, dispersions or emulsions suitable for such administration. The subject agents may also be formulated into polymers for extended release fol low ing parenteral

adm inistration. Pharmaceutically acceptable formulations and ingredients wi l l typical ly be sterile or readi ly sterilizable, biological ly inert, and easi ly

administered. Such polymeric materials are well known to those of ordinary sk i l l in the pharmaceutical compounding arts.

The formulations described herein may be manufactured and sold in a variety of forms. In some embodiments, they may be manu factured and sold as a single strength beverage for direct consumption by the consumer. In other embodiments. the formulations may be sold in an aqueous concentrate to be di luted w ith water to y ield a beverage that treats or prevents acidosis, symptoms of acidosis, and conditions caused by or exacerbated by acidosis. The formulations may also be sold as a powder, granule formation, or tablet which is to be dissolved in w ater to yield a beverage that treats or prevents acidosis, symptoms of ac idosis, and conditions caused or exacerbated by acidosis. In other embodiments, the formu lations described herein may be manufactured and sold in forms suitable for topical adm inistration such as in the form of a lotion, gel, emol l ient, emulsion or cream.

In some embodiments, l iquid formulations as described herein may be sold as part of a kit including a lact ic acid meter, uric ac id meter and/or pH test strips. The pi I test strip would be effective between a pH of 4.5 and 9.0, with measurements in increments of 0.25. The kits of the present invention comprise one or more compositions of the present invention together with the lactic acid meter, uric acid meter and/or pH test strips, information which in forms a user of the kit, by words, pictures, and / or the like, that use of the kit wil l provide one or more general health and / or general physiological benefits including, but not l im ited to, alkal ine increasing, health and performance optimizi ng, i llness preventing, energy level increasing, hydration increasing, recovery time decreasing, muscle protecting and stam ina increasing benefits and which informs the user of the method of monitoring individual acidosis levels. By way of example only, the kit may comprise 7 bottles of .5L of diluted alkaline water at a pi I of 7.5. In other embodiments, the kit may comprise 7 bottles of concentrated alkal ine water in 30m L bottles at a pH of 12.5.

In other embodiments, the formulations described herein suitable for topical adm inistration may be sold in a kit as part of a bandage or other flexible support in which the formulation is impregnated into the fibers.

fhe invention disclosed herein will also be understood to encompass methods and compositions comprisi ng a base solution using in vivo metabol ic products of the said compounds (either generated in vivo after adm inistration of the subject precursor compound, or directly administered in the form of the metabol ic product itself). Such products may result, for example, from the oxidation, reduction, hydrolysis, am idation. esteirification and the l ike of the administered compound, primari ly due to enzymatic processes. Accordingly, the invention includes methods and compositions of the invention employing compounds produced by a process comprising contacting a base solution of the present invention with a mammal ian subject for a period of time sufficient to yield a metabolic product thereof.

The above disclosure generally describes the present invention. Λ more complete understanding can be obtai ned by referring to the fol lowing examples. These examples are described solely for purposes of il lustration and are not intended to l imit the scope of the invention. Although speci fic terms have been employed herein, such terms are intended for descriptive use and not for purposes of l imitation. Examples

As demonstrated in the examples below, the present invention relates to the creation of a strong base solution for use as an antioxidant and/or alkalinity increasing agent.

Example ί

Preparation of Basic Solution

50,000 g of Ca(OH)₂ is added to 500 gallons of water (lOOg/gal) in a polyurethane tank surrounded by strong mono-polar magnets. The mixture is stirred until maximum disassocialion is achieved. The solution is then passed through a 10 micron filter to remove any particulates. 78ml of concentrated sulfuric acid (Baume 12°) per gallon, (39000 ml total) is added to a second polyurethane tank containing 500 gallons of pure water. The acid solution is circulated through an OzoTech OZ2PCS ozone generator (OzoTech, Inc., Yreka, CA) until the pi 1 of the solution is above 7.0. I he diluted sulfuric acid is then added to the filtered Ca(OH)₂ solution and the reaction is allowed to go to completion. The resulting solution is passed through a 10 micron filter to remove any anhydrous calcium sulfate.

Example II

Additional purification of Ca(QI I)? solution

The solution of Example 1 is chilled to below 36^° F. for up to four hours, but not allowed to freeze completely. The partially frozen material is then filtered using a 6 micron filter to remove any newly precipitated anhydrous calcium sulfate and/or ice. This increases the negative charge and the molar strength of the solution.

Example III

Preparation of an antioxidant solution The solution of Example I is added to non-chlorinated drinking water and diluted until a pi 1 of 8.5 to 9.0 is achieved.

Example IV

Treatment for increasing physiological pl l The solution of Example III is administered at the rate of 8 ounces every four hours until 24 to 32 ounces of the solution is consumed. Consumption of this amount increases physiological pH to normal levels and decreases rates of infection. Example V

T^'reatment of Fungal infections

Solutions of the basic solution of Example 1, diluted to a pU of 1 1 , were applied topically once a day to areas of tinea infection. The solut ion controlled the infection and prevented it from spreading.

Example VI

Preparation and use of an antioxidant solution

An alcohol extraction of Dwarf M istletoe, Arceuthobium campyopodum, was prepared to extract myricetin-3-0-galactoside and quercitin-3-O-galactoside. The berries of the Dwarf M istletoe were harvested and then ground into a coarse powder. The powder was then placed in an Erlenmeyer flask with 80% cold methanol. After 24 hours, the methanol wa decanted and saved, and a second aqueous extraction was carried out for a further 24 hours. The combined methanol eluents were evaporated under vacuum leaving an aqueous solution. A half ounce of the aqueous solution was then combi ned with I l iter of the solution of Example I which had been diluted to a p U of 1 1 . The resu lting solution may then be taken over 8 hours.

Example VI I

Preparation of Alkal ine Water solution using calcium oxide 3.2 g of calcium oxide (CaO) was added to one l iter of distilled or m ineral free w ater. The m ixture was stirred for approximately ten m in utes and fi ltered with a non-charcoal five micron A lter resulting in water with a total alkal init of 2000 mg/L CaC03.

Example VI I I

Preparation of Extra strength Alkal ine Water solution using calcium oxide 4 grams of calci um oxide (CaO) were added to one liter of distil led or mineral free water. T he m ixture was stirred for approximately ten min utes and then Altered with a non-charcoal five m icron A lter resulting in water with a 2400 mg/L CaCC total alkalinity .

Example I X

Preparation and use of concentrated calcium ox ide based alkal ine water solution 1 oz of the concentrate of Example VI I I or VI I I was diluted in 32 oz of purified, dem ineral ized or distillled water. A mammal ian subject consumes 8 ounces every four hours until 24 to 32 ou nces of the solution is consumed. Consumption of this amount increases physiological pH to normal levels and decreases rates of infection.

Example X

Preparation of concentrated Alkaline Water using Calcium Oxide-version 2 Five gallons of filtered water are added to a non-reactive drum fitted with a bucket mixer. While stirring, calcium oxide is added until the solution reaches a pi I of 12.75pll as determined by a Waterproof EcoTestr pH 2 (Oakton Instruments. Vernon Hills, IL) and has a conductivity of between 700.S/cm to 750nS/cm as determined by COM- 100: Waterproof EC / IDS / Temp Combo Meter (HM Digital, Inc., Culver City. CA). The resulting solution is then filtered with a non- charcoal five micron filter and decanted into 30mL containers for distribution.

Example XI

Dilution of Alkaline Water for consumption

Five gallons of filtered water are added to a non-reactive drum fitted with a bucket mixer. While stirring, calcium oxide is added until the solution reaches a pi I of

12.75pH as determined by a Waterproof EcoTestr pFl 2 (Oakton Instruments. Vernon Hills. IL) and has a conductivity of between 70(ty.S/cm to 750nS/cm as determined by COM- 100: Waterproof EC / TDS / Temp Combo Meter (I IM Digital, Inc., Culver City, CA). 30mL of the resulting solution is put in a second non-reactive drum fitted with a bucket mixer and add water. The resulting solution has a pH of 7 as determined by a WaterproofEcoTestr pH 2 (Oakton Instruments, Vernon Hills, IL) and has a conductivity of 50 5 as determined by COM- 100: Waterproof EC / TDS / Temp Combo Meter (HM Digital, Inc., Culver City. CA. The solution is filtered with a non-charcoal five micron filter and then decanted into 16.9 oz (.5L) containers for consumption.

Example XI 1

Preparation of Alkaline water using Sodium Hydroxide Five gallons of filtered water are added to a non-reactive drum fitted with a bucket mixer. While stirring, sodium hydroxide is added until the solution reaches a pH of 12.5pH as determined by a Waterproof EcoTestr pH 2 (Oakton Instruments,

Vernon Hills, IL) and has a conductivity of between

as determined by COM- 100: Waterproof EC / TDS / Temp Combo Meter (HM Digital, Inc., Culver City, CA). Example XIII

Preparation of Alkaline water using calcium oxide -version 3 In a 5 gallon non-reactive drum fitted with a mixing device, 9.5 g of calcium oxide is added to 18.9 liters of distilled water and thoroughly mixed at 26.6°C. The pH of the resulting mixture is measured using a Waterproof EcoTestr pH 2 (Oakton Instruments, Vernon Hills, IL). If the pH is less than 12.5, calcium oxide is added by milligram s until the desired pH is achieved. The conductivity of the resulting solution is then measured using a COM- 100: WaterproofEC / TDS / Temp Combo Meter (HM Digital, Inc., Culver City, CA) and is between

7( S/cm and 75(^S/cm.

Example XIV

Preparation of concentrated Alkaline water using Calcium Oxide-version 4 In a 1.5 glass liter beaker, 500 mg of calcium oxide is added to 1 liter of water and mixed thoroughly at 26.6°C. The pH of the resulting mixture is measured using a Waterproof EcoTestr pH 2 (Oakton Instruments, Vernon Hills, IL). If the pi I is less than 12.5, calcium oxide is added by milligrams until the desired pi 1 is achieved. The conductivity of the resulting solution is then measured using a COM- 100: WaterproofEC /TDS /Temp Combo Meter (HM Digital, Inc., Culver City, CA) and is between 700 and 750μ8.

Example XV

Alkaline Gel

9.5 g of calcium oxide were added to 18.9 liters of distilled water in a sterilized mixing container and stirred thoroughly. To the resulting suspension was added 591.5g of xanthan gum and blended until smooth. Then 1 liter of 98% isopropyl alcohol and 28.35g of lemon oil were added and mixed well. The resulting mixture was then packaged in 0.23L (8 oz) sterile containers.

Example XVI

Treatment of nail infections

Nails are soaked in a solution of 1 oz of the alkaline water solution of Example X mixed with one ounce of water for thirty minutes once a day. The nails are then coated with alkaline gel of Example XV. Example XVII

Orange Gel

9.5 g of calcium oxide were added to 18.9 liters of distilled water in a sterilized mixing container and stirred thoroughly. To the resulting suspension was added 591.5g of xanthan gum and blended until siriooth. Then 1 liter of 98% isopropvl alcohol and 28.35g of organic orange oil were added and mixed well. The resulting mixture was then packaged in sterile containers.

Example XVIII

Treatment of MRSA

ethicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It generally causes skin infections similar to boils, but can also infect the blood stream, lungs, or the urinary tract. For a skin infection, Alkal ine gel of Example XV or XVII is liberally applied to the site of infection at least three times per day until the infection is resolved.

Example XIX

Determination ol^" effectiveness of Alkaline Water Ten (10) healthy male subjects ranging from 25 to 35 years old are given 2 L of water in 0.5L doses as a placebo for three days. They are then given 2L of Alkaline water in 0.5L doses every four hours as prepared in Example XI daily for two weeks. On days three, seventeen, and eighteen the subjects undergo aerobic performance assessment on a stationary exercise bicycle in which power is increased from 25 watts to 175 watts at 25 watt intervals. Each interval lasts three minutes. At the end of each interval, peripheral blood is collected to measure lactic acid and anaerobic tolerance. Peripheral blood is collected at 5 minutes, 30 minutes, 1 hour and 24 hours after the last interval. Subjects have continuous heart rate VO2 and CO?, monitoring. Lactic acid levels are measured using a Lactic Acid meter (Sports Resource Group (Hawthorne, NY)).

Example XX

Determination of change in Lactic Acid Threshold Ten (10) healthy males participate in this trial. Subjects warm up for 15 minutes on a stationary bike and then work to their peak sustained intensity within the first 10 minutes and continue for twenty minutes. Using a heart rate monitor, the average heart rate is calculated over the last 20 minutes. Each subject is then given 2L of Alkaline water in 0.5L doses taken four times a day as prepared in Example XI daily for two weeks. After two weeks, the subjects are retested and the average heart rate (estimated heart rate at subject's lactate threshold) is compared.

Although the foregoing invention has been described in detai l by way of example for purposes of c larity of understanding, it will be apparent to the artisan that certain changes and modifications may be practiced within the scope of the appended claims which are presented by way of illustration not lim itation. In this context, various publ ications and other references have been cited with the foregoing d isclosure for economy of description. Each of these references is incorporated herein by reference in its entirety for al l purposes. It is noted, however, that the various publ ications discussed herein are incorporated solely for their disclosure prior to the fi l ing date of the present application, and the inventors reserve the right to antedate such d isclosure by virtue of prior invention.

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Claims

We claim:

A method for preparing a resultant m ixture having a high concentration of OH- ions comprising:

a) preparing a first solution by adding calcium oxide to water;

b) agitating the first solution to increase a rate or amount of dissociation of the calcium oxide;

c) measuring the pH of the first solution; wherein if the pl l of the solution is less than 1 2.5, an additional amount of ca lcium oxide is added to the first solution to create a second solution;

d) agitating the second solution to increase a rate or amount of dissociation of the calcium oxide; and

e) measuring the pi I of the second solution to determ ine that it has a pi I of about 12.5.

2. The method of claim I , wherein the second solution has a conductivity from about 7t^S/cm to about 200u^S/cm.

3. The method of claim of claim 1 , wherein the second solution has a conduct ivity from about 700μ$/α to about 75(^S/cm.

4. Λ method for preparing a resultant m ixture having a high concentration of 01 1- ions comprising:

a) preparing a first solution by adding calcium oxide to water;

c) measuring the pl l of the first solution; wherein i f the pH of the solution is less than 1 2.5, an additional amount of calcium oxide is added to the first solution to create a second solution;

d) agitating the second solution to increase a rate or amount of dissociat ion of the calcium oxide;

e) measuring the pH of the second solution to determ ine that it has a pH of about 1 2.5 ; and

0 diluting the second solution with water so that it has a pi I of about 7.5.

5. The method of claim 4, wherein the resultant mixture has a conductivity of about 6C^iS/cm

6. A method of increasing alkalinity in a mammalian subject suffering from acidosis comprising: a) preparing a first solution by adding calcium oxide to water;

c) measuring the pH of the first solution; wherein if the pH of the solution is less than 12.5, an add itional amount of calcium oxide is added to the first solution to create a second solution;

e) measuring the pi I of the second solution to determ ine that it has a pH of about 1 2.5.

i) diluting the second solution to a pH of about 7.5 to produce a d iluted resultant mixture; and

g) administering an alkalin ity increasing amount of the di luted resultant m ixture to the mammalian subject.

7. The method of claim 6, wherein the di luted resultant m ixture has a conducti vity of about 60μ8/αη.

8. The method of c laim 6, wherein the alkalinity increasing amount comprises between about 1 to about 2 liters of the composition per day.

9. The method of c laim 6, wherein the alkalinity increasing e ffective amount comprises about 0.5 l iters every eight hours.

1 0. Λ method of lowering serum lactic acid levels comprising adm inistering an effective amount of an alka lizing composition in 0.5 L servings wherein a 0.5 l iter serving comprises:

0.5 l iters of a di lution to a pH of 7.5 of a first solution prepared by adding between about 500 ing to about 600 mg of calcium oxide to a liter of water and agitating the fi rst solution to increase a rate or amount of dissociation of the calcium oxide.

I 1 . The method of c laim 1 0, wherein an effective amount lowers serum lactic acid levels by about 0.5 to about 0. 1 mmol/L.

12. The method of claim 10, wherein an effective amount of an alkal izing composition lowers serum lactic acid levels by about 0.25 to about 0.5 mmol/L .

1 3. A method of treating system ic inilammatory response syndrome comprising administering to a mammalian subject an effective amount of an alkal izing composition prepared by: a) creating a first solution by adding calcium oxide to water;

c) measuring the pH of the first solution; wherein if the pH of the solution is less than 12.5, an additional amount of calcium oxide is added to the first solution to create a second solution;

d) agitating the second solution to increase a rate or am ount of dissociation of the calcium oxide; and

e) measuring the pH of the second solution to determ ine that it has a pH of about 1 2.5 ;

0 diluting the second solution to a pH of about 7.5 to produce a diluted resultant mixture; and

g) administering and effective amount of the diluted resultant mixture to the mammal ian subject.

14. The method of c laim 1 3, wherein the di luted resultant m ixture has a conductivity of about 60μ8/αη.

1 5. The method of c laim 1 3, wherein the effective amount of the alkal izing composition comprises between about 1 to about 2 l iters of the composition per day .

1 6. The method of c laim 1 3. wherein the effective amount of the alkal izing composition comprises about 0.5 liters every four hours.

1 7. A method of treating hyperlactem ia comprising administering to a mammal ian subject an effective amount of an alkalizing com position prepared by

a) creating a first solution by adding calci um oxide to water;

b) agitating the first solution to increase a rate or amount of dissociatior, of the calcium oxide;

c) measuring the pH of the first solution; wherein if the pi I of the solution is less than 12.5, an additional amount of calcium oxide is added to the first solution to create a second solution;

f) diluting the second solution to a pH of about 7.5 to produce a diluted resultant mixture; and g) adm in istering and effective amount of the d iluted resultant mixture tc the mammalian subject.

1 8. The method of claim 1 7, wherein the diluted resultant mixture has a conductivity of about 6C^S/cm.

1 . The method of claim 1 7, wherein the alkalinity increasing amount comprises between about 1 to about 2 l iters of the diluted resultant m ixture per day .

20. The method of claim 1 7, wherein the alkalinity increasing effective amount comprises about 0.5 liters of the diluted resultant m ixture every four hours.

2 1 . The method of claim 1 7, wherein the alkalin ity increasing effective amount is effective to decrease serum lactate levels by about 0.5 to 1 .0 m mol/L.

22. The method of claim 1 7, wherein the alkalin ity increasing e ffective amount is effective to decrease serum lactate levels by about 0.25 to 0.5 mmol/L.

23. Λ method of treating methicill in-resistant Staphylococcus aureus comprising adm inistering to a mammal ian subject an effective amount o f an alkal izing composition prepared by:

a) creating a tlrst solution by adding calcium oxide to water;

b) agitating t he first solution to increase a rate or amount of dissociation of the calcium oxide;

c) mcasuring the pH of the first solution; wherein if the pi 1 of the sol ution is less than 1 2.5, an additional amount of ca lcium oxide is added to the first solution to create a second solution;

e) measuring the pi I of the second solution to determ ine that it has a pH of about 1 2.5 ;

f) di luting the second solution to a pH of about 7.5 to produce a diluted resultant mixture; and

g) administering an effective amount of the diluted resultant m ixture to the mammalian subject.

24. The method of claim 23, wherein the di luted resultant mixture has a conductivity of about 60nS/cm.

25. The method of claim 23, wherein the alkal inity increasing effective amount comprises between about 1 to about 2 liters of the composition per day.

26. The method of c laim 23, wherein the alkalinity increasing effective amount comprises about 0.5 liters every four hours.

27. An alkalizing gel for topical application comprising, based on the total weight,

80-95% water;

.01 -.09% CaO;

1 - 4% thickener; and

2- 5% preservative; and

wherein the sum of the percentages is equal to 1 00%.

28. The alkal izing gel of claim 27, wherein the thickener is xanthan gum, carrageen, alginate, alginic acid, pectin, hyaluronic acid, chondroitin su lfate, gum Arabic, selerorium, gum karaya, gum tragacanth, carboxymethyl-chitin, cel lulose gum, chitosan, cationic guar gum, hydroxyethylcellu lose, starch, dextrins, guar gum, cellulose ethers, carboxymethylchitosan, N-hydroxy-dicarboxyethyl-chitosan, modi fied potato starch, cetyl hydroxyethylcellulose or polyquaternium .

29. The alkalizing gel of claim 28, wherein the thickener is xanthan gum .

30. The alkal izing gel of claim 27, wherein the preservative is ethyl alcohol, methyl alcohol and isopropyl alcohol.

3 1 . The alkal izing gel of c laim 27, further comprising 0.05%-0.3% fragrance.

32. The alkal izing gel of c laim 27, wherein the fragrance is lemon oil.

33. The alkal izing gel of claim 27, wherein the fragrance is orange oi l.

34. A method of treating a methicillin-resistant Staphylococcus aureus infection on the skin of a mammalian subject comprising applying an effective amount of an alkal izing gel to the site of the infection, wherei n the alkalizing gel comprises based on the total weight,

80-95% water;

.0 1 -.09% CaO;

1 -4% thickener; and

2-5% preservative;

wherein the sum of the percentages is equal to 1 00%.

35. The alkal izing gel of claim 3 1 , wherein the thickener is xanthan gum, carrageen, selerorium, alginate, alginic acid, pectin, hyaluronic acid, chondroitin sulfate, gum Arabic, gum karaya, gum tragacanth, carboxymethyl-chitin, cellulose gum, chitosan, cationic guar gum, hydroxyethy lcell ulose, starch, dextrins, guar gum, cellulose ethers, carboxymethylchitosan, M-hydroxy-dicarboxyethyl-chitosan, modified potato starch, cetyl hydroxyethylcellulose or polyquaternium.

36. The alkalizing gel of claim 31, wherein the thickener is xanthan gum.

37. The alkalizing gel of claim 31, wherein the preservative is ethyl alcohol, methyl alcohol and isopropyl alcohol.

38. The alkalizing gel of claim 31, further comprising 0.05-0.2% fragrance.

39. The alkalizing gel of claim 31, wherein the fragrance is lemon oil.

40. The alkalizing gel of claim 31, wherein the fragrance is orange oil.

41. The method of claim 31, wherein the alkalizing gel is on a flexible support.

42. The method of claim 41, wherein the flexible support is a bandage.