Methods and compositions for increasing the anaerobic working capacity in tissues

• US 20040229773A1
• Filed: 11/18/2003
• Published: 11/18/2004
• Est. Priority Date: 08/12/1996
• Status: Active Grant

• Current Assignee: Natural Alternatives International Incorporated (Natural Alternatives LLC)
• Original Assignee: Natural Alternatives Int'l Incorporated
• Inventors: Dunnett, Mark, Harris, Roger
• Granted Patent: US 7,504,376 B2
• Time in Patent Office: Days
• US Class Current: 514/3
• CPC Class Codes: A23L 33/175 Amino acids
• CPC Class Codes: A23P 10/40 free-flowing powder or instant powder, i.e. powder which is reconstituted rapidly when liquid is added A23P10/20, A23P10/30 take 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 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/175 having the group , >N—C(O)—N=N— or , e.g. carbonohydrazides, carbazones, semicarbazides, semicarbazones; Thioanalogues thereof
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• 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 31/385 having two or more sulfur atoms in the same ring
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/4172 Imidazole-alkanecarboxylic acids, e.g. histidine
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/06 Anabolic agents androgens A61P5/26
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention provides compositions comprising beta-alanylhistidine peptides and beta-alanines, and methods for administering these peptides and amino acids. In one aspect, the compositions and methods cause an increase in the blood plasma concentrations of beta-alanine and/or creatine.

Claims

1. A method of increasing anaerobic working capacity in a tissue comprising the following steps:

(a) providing a beta-alanylhistidine dipeptide and a glycine, an insulin, an insulin mimic, or an insulin-action modifier; and

(b) administering the beta-alanine and at least one of the glycine, insulin mimic, or insulin-action modifier to the tissue in an amount effective to increase beta-alanylhistidine dipeptide synthesis in the tissue, thereby increasing the anaerobic working capacity in the tissue.

3. The method of claim 1, wherein the step of administering the beta-alanine and at least one of the glycine, insulin mimic, or insulin-action modifier to the tissue comprises oral administration, administration to a blood or blood plasma or a combination thereof.

4. The method of claim 1, wherein the beta-alanylhistidine dipeptide comprises a carnosine, an anserine, or a balenine.

2. A method of regulating hydronium ion concentrations in a tissue comprising the following steps:

(a) providing a beta-alanylhistidine dipeptide and a glycine, an insulin an insulin mimic, or an insulin-action modifier; and

(b) administering the beta-alanine and at least one of the glycine, insulin mimic, or insulin-action modifier to the tissue in an amount effective to increase the hydronium ion concentration in the tissue.

5. A composition comprising a mixture of a glycine, an insulin, an insulin mimic or an insulin-action modifier, and a composition comprising an amino acid or an active derivative thereof selected from the group consisting of a beta-alanine, a chemical derivative of beta-alanine and a peptide comprising a beta-alanine.

6. The composition of claim 5, wherein the beta-alanine comprises a beta-alanylhistidine dipeptide.

7. The composition of claim 6, wherein the beta-alanylhistidine dipeptide comprises a carnosine, an anserine or a balenine.

8. The composition of claim 5, further comprising at least a creatine or a carbohydrate.

9. The composition of claim 5, wherein the insulin mimic comprises a D-pinitol (3-O-methyl-chiroinositol), a 4-hydroxy isoleucine, a demethyl-asterriquinone B-1 compound, an alpha lipoic acid, a R-alpha lipoic acid, a guanidiniopropionic acid, a vanadium compound, a vanadium complex or a synthetic phosphoinositolglycan peptide.

10. The composition of claim 5, wherein the insulin-action modifier is a sulphonylurea, a thiazolidinedione or a biguanide.

11. The composition of claim 5, wherein the composition is a pharmaceutical composition.

12. The composition of claim 5, wherein the composition is a dietary supplement or a sports drink.

13. The composition of claim 12, wherein the dietary supplement or sports drink is a supplement for humans.

14. A composition comprising at least 0.2, 0.3, 0.4, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5 or 5 grams of a peptide or an ester comprising a beta-alanine.

16. The composition of claim 14 or claim 15, wherein the peptide comprises a beta-alanylhistidine dipeptide.

17. The composition of claim 16, wherein the beta-alanylhistidine dipeptide comprises a carnosine, an anserine or a balenine.

15. A composition comprising at least 0.2, 0.3, 0.4, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 grams of a peptide or an ester comprising a beta-alanine in an injectable form.

18. A composition for humans comprising at least 200, 250, 300, 450, 500, 550, 600, 650, 700, 750 or 800 mg of a beta-alanine.

19. The composition of claim 18, wherein the composition is formulated in an ingestible or an injectable formulation.

20. The composition of claim 19, wherein the ingestible formulation is a drink, a gel, a food or a tablet.

21. The composition of claim 18, wherein the peptide comprises a beta-alanylhistidine dipeptide.

22. The composition of claim 20, wherein the beta-alanylhistidine dipeptide comprises a carnosine, an anserine or a balenine.

23. A method of increasing the anaerobic working capacity of a tissue in a subject comprising the following steps:

(a) providing a composition comprising (i) a mixture of a glycine, an insulin, an insulin mimic or an insulin-action modifier, and a composition comprising an amino acid or an active derivative thereof selected from the group consisting of a beta-alanine, a chemical derivative of beta-alanine and a peptide comprising a beta-alanine;

(ii) at least 0.5 gram of a peptide or an ester comprising a beta-alanine in an injectable form;

or, (iii) at least 200 mg of a beta-alanine; and

(b) administering the composition to the subject in an amount effective to increase the anaerobic working capacity of the tissue.

24. The method of claim 23, wherein the total dosage of the beta-alanine for a 24-hour period is at least 0.2 gram.

25. The method of claim 23, wherein the total dosage of the beta-alanine for a 24-hour period is between about 0.2 gram and about 6.4 gram.

26. The method of claim 23, wherein the composition is given over a period of at least 3 days.

27. The method of claim 23, wherein the composition is given over a period of at least about 3 days to about two weeks.

28. The method of claim 23, wherein the beta-alanine comprises a beta-alanylhistidine dipeptide.

29. The method of claim 28, wherein the beta-alanylhistidine dipeptide comprises a carnosine, an anserine or a balenine.

30. The method of claim 28, where the total dosage of the beta-alanylhistidine dipeptide over a 24 hour period is at least about 0.5 gram.

31. The method of claim 30, where the total dosage of the beta-alanylhistidine dipeptide over a 24 hour period is greater than about 5 gram.

32. The method of claim 28, where the total dosage of the beta-alanylhistidine dipeptide over a 24 hour period is more than about 5 gram to about 16 gram.

33. The method of claim 28, where the total dosage of the beta-alanylhistidine dipeptide over a 24 hour period is at least 16 gram.

34. The method of claim 23, wherein the composition is administered in multiple doses.

35. The method of claim 34, wherein the composition is administered at least two times to eight times in a 24-hour period.

36. The method of claim 23, wherein about 200 mg of a beta-alanine or about 500 mg of carnosine is administered about two to eight times a day over a period of several weeks.

37. The method of claim 23, wherein at least about 2 g of a beta-alanine or at least about 5 g of carnosine is administered about two to eight times a day over a period of about two, three or four days.

38. The method of claim 23, wherein the amount of the composition administered is increased daily.

39. The method of claim 23, wherein the amount of the composition administered is increased weekly.

40. The method of claim 23, wherein the composition is administered in treatment periods that last for at least about four weeks.

41. A method of regulating hydronium ion concentration in tissue in a subject comprising the following steps:

(a) providing a composition comprising (i) a mixture of a glycine, an insulin, an insulin mimic or an insulin-action modifier, and a composition comprising an amino acid or an active derivative thereof selected from the group consisting of a beta-alanine, a chemical derivative of beta-alanine and a peptide comprising a beta-alanine;

(ii) at least 0.5 gram of a peptide or an ester comprising a beta-alanine in an injectable form;

or, (iii) at least 200 mg of a beta-alanine; and

(b) administering the composition to the subject in an amount effective to regulate the hydronium ion concentration in the tissue.