COMPOSITIONS, METHODS, AND KITS FOR REGULATING ENERGY METABOLISM

• US 20130237605A1
• Filed: 10/26/2012
• Published: 09/12/2013
• Est. Priority Date: 03/08/2012
• Status: Active Grant

• Current Assignee: Nusirt Sciences, Inc.
• Original Assignee: Nusirt Sciences, Inc.
• Inventors: Zemel, Michael, Grindstaff, E. Douglas II
• Granted Patent: US 9,198,454 B2
• Time in Patent Office: Days
• US Class Current: 514/635
• CPC Class Codes: A23L 33/15 Vitamins
• CPC Class Codes: A23L 33/175 Amino acids
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/332 Promoters of weight control and weight loss
• CPC Class Codes: A23V 2250/0628 Leucine
• CPC Class Codes: A23V 2250/7052 Vitamin B6
• 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 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/191 having two or more hydroxy groups, e.g. gluconic acid
• 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 31/4415 Pyridoxine, i.e. Vitamin B6 pyridoxal phosphate A61K31/675
• 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 3/10 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

The present invention provides for compositions, methods and kits for regulating energy metabolism. In one aspect, the invention provides for compositions that comprise a combination of (a) branched chain amino acids, such as leucine, and (b) vitamin B6, or any precursors or metabolites of (a) or (b). These combinations may be synergistic and/or effective for reducing weight or adipose volume. In another aspect, the invention provides for methods of regulating energy metabolism by the administration of one or more compositions comprising branched chain amino acids and vitamin B6. The invention also provides for kits comprising compositions of branched chain amino acids and vitamin B6 packaged in an oral dose form with usage instructions.

Claims

1. A container comprising multiple unit dosages, each unit dosage comprising:

(a) leucine and/or a leucine metabolite selected from the group consisting of keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and hydroxymethylbutyrate (HMB), and

(b) vitamin B6,

wherein the mass ratio of component (a) to (b) in each unit dosage is greater than about 65, wherein each unit dosage comprises at least about 250 mg leucine and/or leucine metabolite and at least about 0.1 mg of vitamin B6,

wherein each unit dosage comprises less than 1% of the individual amino acids isoleucine and valine.

2. The container of claim 1, wherein the multiple unit dosages when administered to a cell enhance energy metabolism of said cell to a greater degree than component (a) or component (b) when used alone, and wherein the enhanced energy metabolism is measured by an increase in fatty acid oxidation of myotube by at least about 140%, an increase in fatty acid oxidation of an adipocyte by at least about 450%, an increase in glucose utilization of an adipocyte by at least 150%, an increase in glucose utilization of an adipocyte by at least 200%, an increase in Sirt1 expression in a myotube by at least about two-fold, an increase in AMPK activation in a myotube by at least about two-fold, and/or an increase in mitochondrial biomass in a myotube by at least about 50%, when (i) media from the myotube or adipocyte treated with the composition is administered to the other of the myotube or adipocyte or (ii) the composition is administered to the myotube or adipocyte.

3. The container of claim 1, wherein, upon administration to a subject, the multiple unit dosages enhance energy metabolism in the subject to a greater degree than administering to the subject component (a) or component (b) alone and the enhanced energy metabolism is measured by an increase in weight loss of a subject by at least 40%, an increase in fat loss of a subject by at least about 50%, an increase in fat loss of a subject by at least about 50%, or an increase in insulin sensitivity by at least about 15%, an increase in fat oxidation by at least about 60%, or a decrease in oxidative stress markers by at least about 15%, when the composition is administered to the subject.

4. The container of claim 1, wherein each unit dosage comprises less than about 1% of the individual amino acids methionine and tryptophan.

5. The container of claim 1, wherein, upon administration to a subject, the multiple unit dosages enhances energy metabolism in the subject to a greater degree as compared to the sum of the effects of administering component (a) alone and component (b) alone, as if each component (a) and (b) exerted its effect independently.

6. The container of claim 1, wherein, upon administration to a cell, the multiple unit dosages enhances a) fatty acid oxidation of a myotube by at least about 50% or b) glucose utilization of a myotube by at least about 150% greater than the predicted additive effect of administering each component alone, as if each component exerted its effect independently.

7. The container of claim 1, wherein each unit dosage comprises at least about 250 mg of leucine and at least about 5 mg of vitamin B6.

8. The container of claim 1, wherein each unit dosage is a dietary supplement packaged as a solid food or semi-solid food.

9. The container of claim 1, wherein each unit dosage is formulated as an oral dosage form.

10. The container of claim 1, wherein each unit dosage further comprises a food carrier.

12. The container of claim 1,

wherein each unit dosage comprises at least about 500 mg of leucine and at least about 5 mg of vitamin B6.

13. The container of claim 1,

wherein each unit dosage is formulated as a tablet, capsule, or gel capsule.

14. The container of claim 1, wherein each unit dosage further comprises a pharmaceutically active agent or an anti-diabetic agent.

15. The container of claim 1, wherein each unit dosage further comprises metformin.

16. The container of claim 1, wherein each unit dosage is a pharmaceutical composition further comprising a pharmaceutically acceptable excipient.

17. The container of claim 1, wherein the mass ratio of component (a) to (b) in said composition is less than about 100.

19. The method of claim 28, wherein the subject is a domesticated animal.

27. The container of claim 1 packaged in the form of a kit comprising a multi-day supply of the unit dosages, and instructions directing the administration of said multi-day supply over a period of multiple days.

28. A method for increasing energy metabolism in a subject in need thereof comprising administering a unit dosage of claim 1 to the subject to effect an increase in the subject'"'"'s energy metabolism.

30. A method for increasing energy metabolism in a subject comprising:

administering a unit dosage of claim 1 at a selected dosing level, wherein the selected dosing level induces a circulating level of about 0.5 mM leucine and about 100 nM B6 in the subject.

18. A liquid composition comprising:

(a) at least about 250 mg of leucine and/or a leucine metabolite per 16 ounces of the liquid composition; and

(b) vitamin B6,

wherein the leucine metabolite is selected from the group consisting of keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and hydroxymethylbutyrate (HMB),

wherein the mass ratio of component (a) to (b) in said composition is greater than about 65, and

wherein the composition comprises less than 1% of the individual amino acids isoleucine and valine.

11. The composition of claim 18,

wherein the composition is packaged as a unit dosage.

20. The composition of claim 18, wherein component (a) is present in an amount of at least about 250 mg, and component (b) is present in an amount of at least about 0.1 mg.

21. The composition of claim 18, wherein component (a) is present in an amount of at least about 1130 mg, and component (b) is present in an amount of at least about 12 mg.

22. The composition of claim 18, wherein the composition is a dietary supplement packaged as a beverage.

23. The composition of claim 18, wherein the composition comprises less than about 1% of the individual amino acids methionine and tryptophan.

24. The composition of claim 18, further comprising one or more of a sweetener, a bulking agent, a stabilizer, an acidulant, and a preservative.

25. The composition of claim 18, wherein the composition has a shelf-life greater than 7 months.

26. The composition of claim 18, wherein the composition is in a container and is nonperishable at room temperature for at least one hour after opening.

29. A method for enhancing fat oxidation in a subject in need thereof comprising administering the composition of claim 18 at least two times per day to effect an increase in the subject'"'"'s fat oxidation.