METHOD TO REDUCE OXIDATIVE DAMAGE AND IMPROVE MITOCHONDRIAL EFFICIENCY

• US 20070135376A1
• Filed: 06/15/2006
• Published: 06/14/2007
• Est. Priority Date: 06/20/2005
• Status: Abandoned Application

• Current Assignee: Accela Incorporated (Piksel Incorporated)
• Original Assignee: Accela Incorporated (Piksel Incorporated)
• Inventors: Henderson, Samuel
• Application Number:
  US11/424,429
• Publication Number:
  US 20070135376A1
• Time in Patent Office: Days
• US Class Current: 514/52
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61K 31/23 of acids having a carboxyl group bound to a chain of seven or more carbon atoms
• CPC Class Codes: A61K 31/33 Heterocyclic compounds
• CPC Class Codes: A61K 31/683 Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Methods for the reduction of mitochondrial oxidative damage and improved mitochondrial efficiency in an animal by administration of medium chain triglycerides or prodrug of medium chain triglycerides to the animal are provided.

Claims

1. A method of modulating mitochondrial function in a mammal, comprising administering to the mammal an effective amount of an agent which induces development of ketosis in the mammal, whereby mitochondrial function is modulated.

2. The method claim 1, wherein said agent comprises medium chain triglycerides.

3. The method of claim 2, wherein modulating mitochondrial function comprises reducing oxidative damage or improving mitochondrial efficiency.

4. The method of claim 2, further comprising detecting the modulation of mitochondrial function.

5. The method of claim 4, wherein the detecting comprises detecting modulation of State I respiration, detecting modulation of State II respiration, detecting modulation of State III respiration, detecting modulation of State IV respiration, detecting modulation of RCR, detecting modulation of uncoupling protein activity, detecting lipid oxidation, and detecting protein oxidation.

6. The method claim 2, wherein said medium chain triglycerides are administered medium chain triglycerides are administered at a dose of about 0.1 g/kg/day to about 10 g/kg/day.

7. The method of claim 6, further comprising coadministering L-carnitine or a derivative of L-carnitine.

8. The method claim 7, wherein said L-carnitine or said derivative of L-carnitine is administered at a dose of about 0.5 mg/kg/day to about 10 mg/kg/day.

9. The method of claim 2, wherein said medium chain triglycerides are emulsified.

10. The method of claim 9, further comprising coadministering L-carnitine or a derivative of L-carnitine.

11. The method of claim 10, wherein said emulsified medium chain triglycerides and L-carnitine or a derivative of L-carnitine are administered in a formulation comprising 10-500 g emulsified medium chain triglycerides and 10-2000 mg L-carnitine or derivative of L-carnitine.

12. The method of claim 2, wherein the agent further comprises a ketone body or metabolic precursor of a ketone body.

13. The method of claim 12, wherein the ketone body is selected from a group consisting of β

-hydroxybutyrate, acteoacetate, metabolic precursors of β

-hydroxybutyrate or acteoacetate, and mixtures thereof.

14. The method of claim 13, wherein the metabolic precursor is a physiologically acceptable salt or ester of a polymer or oligomers wherein in each case the number of subunit repeats is selected such that the polymer or oligomers is readily metabolized on administration to a human or animal to provide elevated ketone body levels in the blood.

15. The method of claim 14, wherein the metabolic precursor is selected from the group consisting of:

wherein n is an integer of 0 to 1,000, and m is an integer of 1 or more, a complex thereof with one or more cations or a salt thereof for use in therapy or nutrition.

16. The method of claim 2, wherein the agent further comprises a metabolic adjuvant.

17. The method of claim 16, wherein the adjuvant is selected from a group consisting of a vitamin, a mineral, an antioxidant, and energy-enhancing compound, and mixtures thereof.

18. The method of claim 17, wherein the energy-enhancing compound is selected from a group consisting of Coenzyme CoQ-10, creatine, L-carnitine, n-acetyl-carnitine, L-carnitine derivatives, and mixtures thereof.

19. The method of claim 17, wherein the vitamin is selected from a group consisting of ascorbic acid, biotin calcitriol, cobalamin, folic acid, niacin, pantothenic acid, pyridoxine, retinol;

retinal (retinaldehyde), retinoic acid, riboflavin, thiamin, benfotiamine, a-tocopherol, phytylmenaquinone, multiprenylmenaquinone, pyridoxine derivatives, pantothenic acid, and mixtures thereof.

20. The method of claim 17, wherein the mineral is selected from a group consisting of calcium, magnesium, sodium, potassium, zinc, copper, aluminum, chromium, vanadium, selenium, phosphorous, manganese, iron, fluorine, cobalt, molybdenum, iodine and mixtures thereof.

21. The method of claim 6 wherein the agent further comprises a triglyceride containing an essential fatty acid from a group consisting of 18:

2 n-6 (linoleic), 18;

3 n-6, 20;

3 n-6, 20;

4 n-6 (arachidonic), 24;

4 n-6, 24;

5, n-6, 22;

5 n-6, 18;

3 n-3 (alpha-linolenic), 18;

4 n-3, 20;

4 n-3, 20;

5 n-3 (eicosapetaenoic), 22;

5 n-3, 24;

5 n-3, 24;

6 n-3, 22;

6 n-3 (docosahexanoic).