COMPOSITIONS FOR TREATING OR PREVENTING OBESITY AND INSULIN RESISTANCE DISORDERS

• US 20100316679A1
• Filed: 01/07/2010
• Published: 12/16/2010
• Est. Priority Date: 12/29/2003
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation), The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Alexander-Bridges, Maria, Sinclair, David A.
• Granted Patent: US 8,242,171 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

Provided herein are methods and compositions for modulating the activity or level of a sirtuin, thereby treating or preventing obesity or an insulin resistance disorder, such as diabetes in a subject. Exemplary methods comprise contacting a cell with a sirtuin activating compound or an inhibitory compound to thereby increase or decrease fat accumulation, respectively.

Claims

1-29. -29. (canceled)

30. A method for treating an insulin resistance disorder in a human, comprising administering to a human in need thereof a therapeutically effective amount of a pharmaceutical composition consisting essentially of resveratrol.

31. The method of claim 30, wherein the insulin resistance disorder is type II diabetes.

32. The method of claim 30, wherein the insulin resistance disorder is insulin resistance.

33. The method of claim 30, wherein the insulin resistance disorder is metabolic syndrome.

34. The method of claim 30, further comprising administering to the subject a second agent that:

increases the activity or protein level of a sirtuin;

increases the activity and/or protein level of 5′

-AMP-activated protein kinase (AMPK) in a cell;

is an anti-diabetic agent;

or is an anti-obesity agent.

35. The method of claim 34, wherein the second agent is an anti-diabetic agent.

36. The method of claim 30, wherein the pharmaceutical composition comprises one or more pharmaceutically acceptable carriers.

37. The method of claim 36, wherein the one or more pharmaceutically acceptable carriers is/are one or more liquid or solid fillers, diluents, excipients, solvents or encapsulating materials selected from the group consisting of:

sugars, optionally lactose, glucose and/or sucrose;

starches, optionally corn starch and/or potato starch;

cellulose, and its derivatives, optionally sodium carboxymethyl cellulose, ethyl cellulose and/or cellulose acetate;

powdered tragacanth;

malt;

gelatin;

talc;

excipients, optionally cocoa butter and/or suppository waxes;

oils, optionally peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and/or soybean oil;

glycols, optionally propylene glycol;

polyols, optionally glycerin, sorbitol, mannitol and/or polyethylene glycol;

esters, optionally ethyl oleate and/or ethyl laurate;

agar;

buffering agents, optionally magnesium hydroxide and/or aluminum hydroxide;

alginic acid;

pyrogen-free water;

isotonic saline;

Ringer'"'"'s solution; and

phosphate buffer solutions.

38. The method of claim 30, wherein the resveratrol is not in a form that is naturally-occurring.

39. A method for reducing the weight of a subject, or preventing weight gain in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition consisting essentially of resveratrol.

40. The method of claim 39, wherein the pharmaceutical composition comprises one or more pharmaceutically acceptable carriers.

41. The method of claim 40, wherein the one or more pharmaceutically acceptable carriers is/are one or more liquid or solid fillers, diluents, excipients, solvents or encapsulating materials selected from the group consisting of:

sugars, optionally lactose, glucose and/or sucrose;

starches, optionally corn starch and/or potato starch;

cellulose, and its derivatives, optionally sodium carboxymethyl cellulose, ethyl cellulose and/or cellulose acetate;

powdered tragacanth;

malt;

gelatin;

talc;

excipients, optionally cocoa butter and/or suppository waxes;

oils, optionally peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and/or soybean oil;

glycols, optionally propylene glycol;

polyols, optionally glycerin, sorbitol, mannitol and/or polyethylene glycol;

esters, optionally ethyl oleate and/or ethyl laurate;

agar;

buffering agents, optionally magnesium hydroxide and/or aluminum hydroxide;

alginic acid;

pyrogen-free water;

isotonic saline;

Ringer'"'"'s solution; and

phosphate buffer solutions.

42. The method of claim 39, wherein the resveratrol is not in a form that is naturally-occurring.

43. A method for preventing fat accumulation in a cell with lipogenic capacity, comprising contacting the cell with a therapeutically effective amount of resveratrol.

44. The method of claim 43, wherein the cell with lipogenic capacity is a liver, pancreas or muscle cells.

45. The method of claim 43, wherein the cell is an adipocyte.

46. The method of claim 43, wherein the cell is in vitro.

47. A method for preventing the differentiation of a pre-adipocyte, comprising contacting the pre-adipocyte with an agent that increases the activity or protein level of a sirtuin in a cell, such that the differentiation of the pre-adipocyte is inhibited.

48. The method of claim 47, wherein the pre-adipocyte is in vitro.

49. A method for treating an insulin resistance disorder in a human, comprising administering to a human in need thereof a therapeutically effective amount of resveratrol and a therapeutically effective amount of metformin.

50. The method of claim 49, wherein the insulin resistance disorder is type II diabetes.

51. The method of claim 49, wherein the insulin resistance disorder is insulin resistance.