COMPOSITIONS AND METHODS FOR MODULATING METABOLIC PATHWAYS

• US 20170312240A1
• Filed: 05/15/2017
• Published: 11/02/2017
• Est. Priority Date: 07/15/2011
• Status: Active Grant

• Current Assignee: Nusirt Sciences, Inc.
• Original Assignee: Nusirt Sciences, Inc.
• Inventors: Zemel, Michael, Grindstaff, II, E. Douglas, Bruckbauer, Antje
• Granted Patent: US 9,855,235 B2
• Time in Patent Office: Days
• CPC Class Codes: A23L 2/52 Adding ingredients adding preservatives A23L2/44
• CPC Class Codes: A23L 33/175 Amino acids
• CPC Class Codes: A23L 33/30 Dietetic or nutritional methods, e.g. for losing weight A23L33/10 takes precedence
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• 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 31/015 carbocyclic
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/191 having two or more hydroxy groups, e.g. gluconic acid
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/336 having three-membered rings, e.g. oxirane, fumagillin
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 36/87 : Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
• CPC Class Codes: A61K 38/22 : Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/02 : Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/48 : of the pancreatic hormones
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications

Abstract

Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions can contain synergizing amounts of a sirtuin-pathway activators, including but not limited to resveratrol, in combination with beta-hydroxymethylbutyrate (HMB), keto isocaproic acid (KIC), leucine, or combinations of HMB, KIC and leucine.

Claims

1-30. -30. (canceled)

31. A method for treating obesity in a subject in need thereof comprising:

a) administering a composition comprising;

i. at least about 500 mg of leucine and/or at least about 200 mg of one or more metabolites thereof, wherein the one or more leucine metabolites are selected from the group consisting of keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and HMB; and

ii. an amount of at least about 0.5 mg of a sirtuin pathway activator,

32. The method of claim 31, wherein the sirtuin pathway activator activates one or more of SIRT1, SIRT3, AMPK, and PGC1α

.

33. The method of claim 31, wherein the sirtuin pathway activator is a hydroxycinnamic acid, a stilbene, a polyphenol or a polyphenol precursor.

34. The method of claim 31, wherein the sirtuin pathway activator is a polyphenol or a polyphenol precursor.

35. The method of claim 34, wherein the polyphenol or polyphenol precursor is selected from the group consisting of chlorogenic acid, resveratrol, caffeic acid, cinnamic acid, ferulic acid, piceatannol, ellagic acid, epigallocatechin gallate, grape seed extract, and any analog thereof.

36. The method of claim 31, wherein the sirtuin pathway activator is resveratrol.

37. The method of claim 31, wherein the sirtuin pathway activator is a phosphodiesterase inhibitor.

38. The method of claim 31, wherein the sirtuin pathway activator is present in a sub-therapeutic amount.

39. The method of claim 31, wherein the amount of the sirtuin pathway activator is no more than 5 mg.

40. The method of claim 31, wherein the amount of the sirtuin pathway activator is no more than 50 mg.

41. The method of claim 31, wherein the molar ratio of component (a) to (b) in said composition is greater than about 20.

42. The method of claim 31, wherein the molar ratio of component (a) to (b) in said composition is greater than about 5.

43. The method of claim 31, wherein the composition further comprises an anti-diabetic agent.

44. The method of claim 43, wherein the anti-diabetic agent comprises metformin.

45. The composition of claim 44, wherein the composition comprises at least about 25 mg of the metformin.

46. The composition of claim 44, wherein the composition comprises at least about 250 mg of metformin.

47. The composition of claim 44, wherein the composition comprises at least about 400 mg of metformin.

48. The method of claim 31, wherein the composition is formulated as a unit dose.

49. The method of claim 31, wherein the composition is formulated as a tablet, capsule, gel capsule, beverage, snack bar or a food composition.

50. The method of claim 31, wherein the composition further comprises at least one pharmaceutically active agent.

51. The method of claim 50, wherein the pharmaceutically active agent is an anti-obesity agent.

52. The method of claim 51, wherein the anti-obesity agent is selected from group consisting of:

lipase inhibitors, dopaminergic compounds, noradrenergic compounds, serotoninergic compounds, cannabinoid receptor antagonists, exenatide, pramlintide, and CNS agents.

53. The method of claim 31, wherein the composition comprises less than about 1% of the individual amino acids alanine, glutamic acid, glycine, and proline.

54. The method of claim 31, wherein the composition is substantially free of an individual non-branched amino acid.

55. The method of claim 31, wherein treating obesity is characterized by a reduction in body weight, weight gain, visceral adipose tissue mass, fat oxidation and heat production, and respiratory exchange ratio.

56. The method of claim 31, wherein the subject in need thereof is on a calorie restricted diet.

57. The method of claim 31, wherein the subject in need thereof is on an unrestricted diet.

58. The method of claim 31, wherein the subject in need thereof is human.

59. The method of claim 31, wherein the composition is administered to the subject twice a day.

60. The method of claim 31, wherein the composition is administered to the subject once a day.

61. A method for reducing body weight or weight gain in a subject in need thereof comprising administering an effective amount of leucine and/or one or more metabolites thereof, and a sirtuin pathway activator.