Compositions and Methods for the Treatment of Metabolic Conditions

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.

1 .- 7 . (canceled) 
     
     
         8 . A method of treating or ameliorating a mitochondrial disorder, metabolic disorder, a condition associated with diabetes or a cardiovascular dysfunction, in a subject in need thereof, the method comprising
 administering to the subject an effective amount of a therapeutic composition comprising
 an intravenous buffer solution comprising at least one pharmaceutical grade acid and 
 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 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, and   wherein the buffer solution is administered in an amount that is sufficient to reduce the physiological bloodstream pH of a subject by 0.01 to 1.1.   
     
     
         9 . The method of  claim 8 , wherein the buffer solution is administered in an amount sufficient to reduce the physiological bloodstream pH of a subject by 0.15 to 0.75. 
     
     
         10 . The method of  claim 8 , wherein the concentration of the acid and buffering agent provide the buffer solution with a buffer capacity sufficient to sustain the reduction of the physiological bloodstream pH of the subject for between 1 minute and 1 week. 
     
     
         11 . The method of  claim 8 , wherein the metabolic disorder is diabetes, insulin resistance, glucose intolerance, hyperglycemia, hyperinsulinemia, obesity, hyperlipidemia, or hyperlipoproteinemia. 
     
     
         12 . The method of  claim 8 , wherein the pharmaceutical grade acid comprises dehydroascorbic acid. 
     
     
         13 . The method of  claim 8 , wherein the composition further comprises one or more of a magnesium ion source, a potassium ion source, and a calcium ion source. 
     
     
         14 . The method of  claim 8 , wherein the composition further comprises one or more of a B vitamin, vitamin C, and vitamin K. 
     
     
         15 . The method of  claim 8 , wherein the composition further comprises antioxidant defense compounds comprising nonenzymatic compounds selected from the group consisting of tocopherol (aTCP), coenzyme Q10 (Q), cytochrome c (C) and glutathione (GSH) and enzymatic components including manganese superoxide dismutase (MnSOD), catalase (Cat), glutathione peroxidase (GPX), phospholipid hydroperoxide glutathione peroxidase (PGPX), glutathione reductase (GR); peroxiredoxins (PRX3/5), glutaredoxin (GRX2), thioredoxin (TRX2), thioredoxin reductase (TRXR2), and a combination thereof. 
     
     
         16 . The method of  claim 8 , wherein the composition is formulated in hypotonic, isotonic, or hypertonic form. 
     
     
         17 . The method of  claim 8 , wherein the composition is administered intravenously, by bolus, dermally, orally, optically, via suppository, buccally, or via inhalation. 
     
     
         18 . The method of  claim 8 , wherein the administering comprises introducing the composition by infusion over a period of about 1 minute to about 1 hour, and the infusion is repeated as necessary over a period of time selected from about 1 day to about 1 year. 
     
     
         19 . The method of  claim 8 , wherein the subject is a human or veterinary subject. 
     
     
         20 . A method of treating chronic wounds of a subject, the method comprising
 administering to the subject an effective amount of a therapeutic composition comprising
 an intravenous buffer solution comprising at least one pharmaceutical grade acid and 
 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 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,   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, and   wherein the buffer solution is administered in an amount that is sufficient to reduce the physiological bloodstream pH of a subject by 0.01 to 1.1.   
     
     
         21 . The method of  claim 20 , wherein the buffer solution is administered in an amount sufficient to reduce the physiological bloodstream pH of a subject by 0.15 to 0.75. 
     
     
         22 . The method of  claim 20 , wherein the concentration of the acid and buffering agent provide the buffer solution with a buffer capacity sufficient to sustain the reduction of the physiological bloodstream pH of the subject for between 1 minute and 1 week. 
     
     
         23 . The method of  claim 20 , wherein the composition further comprises one or more of a magnesium ion source, a potassium ion source, and a calcium ion source. 
     
     
         24 . The method of  claim 20 , wherein the subject is a human or veterinary subject. 
     
     
         25 . A method of removing vascular plaque from the arteries of a subject, the method comprising
 administering to the subject an effective amount of a therapeutic composition comprising
 an intravenous buffer solution comprising at least one pharmaceutical grade acid and 
 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 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,   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, and   wherein the buffer solution is administered in an amount that is sufficient to reduce the physiological bloodstream pH of a subject by 0.01 to 1.1.   
     
     
         26 . The method of  claim 25 , wherein the buffer solution is administered in an amount sufficient to reduce the physiological bloodstream pH of a subject by 0.15 to 0.75. 
     
     
         27 . The method of  claim 25 , wherein the concentration of the acid and buffering agent provide the buffer solution with a buffer capacity sufficient to sustain the reduction of the physiological bloodstream pH of the subject for between 1 minute and 1 week. 
     
     
         28 . The method of  claim 25 , wherein the composition further comprises one or more of a magnesium ion source, a potassium ion source, and a calcium ion source. 
     
     
         29 . The method of  claim 25 , wherein the composition further comprises one or more of a B vitamin, vitamin C, and vitamin K. 
     
     
         30 . The method of  claim 25 , wherein the subject is a human or veterinary subject.