# US 11,077,091 B2 · Compositions and methods for the treatment of metabolic conditions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,091 B2 - Document ID: US11077091B2 - Status: Granted - Kind: B2 - Application number: 16/665,795 - Filed: 2019-10-28 - Published: 2020-04-23 - Granted: 2021-08-03 - Earliest claimed: 2017-12-07 - Assignees: Reven IP HoldCo LLC - Applicants: Reven IP HoldCo LLC - Inventors: James Ervin; Hendrik J. Van Wyk; Brian D. Denomme; Mariette L. Van Wyk; Peter Pacult; Michael A. Volk - Web page: https://patentgrep.com/patent/US11077091B2 ## CPC - A61K 31/375: Ascorbic acid, i.e. vitamin C; Salts thereof - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0048: {Eye, e.g. artificial tears} - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin - A61K 31/197: the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205) - A61K 31/4415: Pyridoxine, i.e. Vitamin B6 (pyridoxal phosphate A61K31/675) - A61K 31/455: Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides - A61K 31/51: Thiamines, e.g. vitamin B1 - A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate - A61K 31/714: Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12 - A61K 33/20: Elemental chlorine; Inorganic compounds releasing chlorine - A61K 47/02: Inorganic compounds - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to stable therapeutic compositions of pharmaceutical grade acids and pH buffering agents. The present invention also is directed to methods of treatment for mitochondrial disorders, metabolic conditions, diabetic conditions, and cardiovascular conditions, by administration of compositions of the present disclosure. ## Claims ### Claim 1 A method of elevating blood oxygen in a subject suffering from hypoxia, the method comprising elevating the pO2 in the venous blood in the subject suffering hypoxia, comprising administering to the subject a stable therapeutic composition comprising an intravenous buffer solution comprising an equilibrium product of mixing at least one pharmaceutical grade acid with at least one pharmaceutical grade pH buffering agent in a sterile aqueous solution, wherein the pharmaceutical grade acid is selected from the group consisting of hydrochloric acid, ascorbic acid, dehydroascorbic acid, acetic acid, citric acid, lactic acid, phosphoric acid, and a combination of two or more thereof, wherein the composition is administered in an amount effective to provide metabolic corrections that promote vasodilation, reduction of intracellular accrual of Ca2+, or stimulate renal and respiratory action to shift blood pH towards alkaline, thereby elevating the subject's blood oxygen to alleviate the hypoxia, wherein the concentration of the pharmaceutical grade acid and the pharmaceutical grade pH buffering agent in the buffer solution is sufficient to provide a total titratable acid content of from 60 mmol/L to 3,000 mmol/L when administered to a subject, and wherein the selection of the pharmaceutical grade acid and the pharmaceutical grade pH buffering agent is effective to provide a buffer solution pH of between 4 and 7.7. ### Claim 2 (depends on 1) The method of claim 1, wherein the buffer solution is administered in an effect amount that is sufficient to reduce the physiological bloodstream pH of a subject by 0.01 to 1.1. ### Claim 3 (depends on 1) The method of claim 1, wherein the buffer solution is sufficient to reduce the physiological bloodstream pH of a subject by 0.15 to 0.75. ### Claim 4 (depends on 1) The method of claim 1, wherein the buffer solution has a buffer capacity sufficient to sustain the reduction of the physiological bloodstream pH of the subject for between 1 minute and 1 week. ### Claim 5 (depends on 1) The method of claim 1, wherein the composition further comprises one or more of a magnesium ion source, a potassium ion source, and a calcium ion source. ### Claim 6 (depends on 1) The method of claim 1, wherein the composition further comprises one or more of a B vitamin, vitamin C, and a K vitamin. ### Claim 7 (depends on 1) The method of claim 1, wherein the subject is a human or veterinary subject. ### Claim 8 (depends on 1) The method of claim 1, wherein the buffer solution is sufficient to reduce the physiological bloodstream pH of a subject by 0.15 to 0.5. ### Claim 9 (depends on 1) The method of claim 1, wherein the buffer solution has a buffer capacity sufficient to sustain the reduction of the physiological bloodstream pH of the subject for between 1 minute and 1 hour. ### Claim 10 (depends on 1) The method of claim 1, wherein the buffer solution has a buffer capacity sufficient to sustain the reduction of the physiological bloodstream pH of the subject for between 1 hour and 1 day. ### Claim 11 (depends on 1) The method of claim 1, wherein the buffer solution has a buffer capacity sufficient to sustain the reduction of the physiological bloodstream pH of the subject for between 1 day and 1 week. ### Claim 12 (depends on 1) The method of claim 1, wherein the pharmaceutical grade acid is selected from the group consisting of hydrochloric acid, ascorbic acid, acetic acid, dehydroascorbic acid, and a combination thereof. ### Claim 13 (depends on 1) The method of claim 1, wherein the pharmaceutical grade pH buffering agent is a bicarbonate. ### Claim 14 (depends on 1) The method of claim 1, wherein the pharmaceutical grade pH buffering agent is selected from the group consisting of a bicarbonate, sodium bicarbonate, a phosphate buffer, sodium hydroxide, organic acid, organic amine, ammonia, citrate buffer, tris-hydroxymethyl amino methane, a synthetic buffer, and a combination thereof. ### Claim 15 (depends on 1) The method of claim 1, wherein said composition comprises 840±84 mg of sodium bicarbonate as said pharmaceutical grade buffering agent, 4.5 ± 0.45 mM of hydrochloric acid, and 900 ± 90 mg of L Ascorbic acid or 100 ± 10 mg of dehydroascorbic acid, or both, as said pharmaceutical grade acid, and per quantity of water sufficient to obtain a final composition volume of 20 mL. ### Claim 16 (depends on 1) The method of claim 1, wherein said composition further comprises: 900 ± 90 mg of L-Ascorbic Acid; 63.33 ± 6.33 mg Thiamine HCl; 808 ± 80.8 mg of Magnesium Sulfate; 1.93 ± 0.193 mg of Cyanocobalamin; 119 ± 11.9 mg of Niacinamide; 119 ± 11.9 mg of Pyridoxine HCl; 2.53 ± 0.253 mg of Riboflavin 5′Phosphate; and 2.93 ± 0.293 mg of Calcium D-Pantothenate per quantity of water sufficient to obtain a final composition volume of 20 mL. ### Claim 17 (depends on 1) The method of claim 1, wherein the intravenous buffer solution comprises a bicarbonate ion (HCO3−) concentration between about 0.5 and about 2.0 M/L. ### Claim 18 (depends on 1) The method of claim 1, wherein the intravenous buffer solution further comprises an antioxidant defense compound selected from the group consisting of a nonenzymatic compound or an enzymatic compound. ### Claim 19 (depends on 18) The method of claim 18, wherein the nonenzymatic compound is selected from the group consisting of tocopherol (aTCT), coenzyme Q10 (Q), cytochrome c (C), glutathione (GSH) and a combination thereof. ### Claim 20 (depends on 18) The method of claim 18, wherein the enzymatic compound is selected from the group consisting of manganese superoxide dismutase (MnSOD), catalase (Cat), glutathione peroxidase (GPX), phospholipid hydroperoxide glutathione peroxidase (PGPX), glutathione reductase (GR), peroxiredoxin (PRX3/5), glutaredoxin (GRX2), thioredoxin (TRX2), thioredoxin reducatase (TRXR2), and a combination thereof. ### Claim 21 (depends on 1) The method of claim 1, wherein the intravenous buffer solution is in a hypotonic, isotonic or hypertonic form. ### Claim 22 (depends on 1) The method of claim 1, wherein the hypoxia is associated with a heart attack, cardiovascular disease, a lung condition, concussive cascade, reperfusion injury, myocardial infarction, diabetes or tissue trauma. ### Claim 23 (depends on 1) The method of claim 1, wherein said composition further comprises one or more ingredients selected from the group consisting of vitamins, salts, acids, amino acids or salts thereof, and stabilized oxidative species. ### Claim 24 (depends on 1) The method of claim 1, wherein said pharmaceutical grade acid comprises ascorbic acid. ### Claim 25 (depends on 1) The method of claim 1, wherein said pharmaceutical grade acid comprises dehydroascorbic acid. ### Claim 26 (depends on 1) The method of claim 1, wherein said composition is lyophilized or frozen. ### Claim 27 (depends on 1) The method of claim 1, wherein said composition is stored in a spectral-blocking vial. ### Claim 28 (depends on 1) The method of claim 1, wherein said composition is formed by combining components from two or more vials.