Synergistic pharmaceutical combinations for treating obesity

• US 20030187055A1
• Filed: 02/25/2003
• Published: 10/02/2003
• Est. Priority Date: 02/25/2002
• Status: Abandoned Application

• Current Assignee: Signal Investment & Management Co. (Sanofi )
• Original Assignee: Signal Investment & Management Co. (Sanofi )
• Inventors: Riker, Donald K., Law, Michael Y.
• Application Number:
  US10/373,726
• Publication Number:
  US 20030187055A1
• Time in Patent Office: Days
• US Class Current: 514/419
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

This invention relates to a novel composition which contains 5-hydroxytryptophan (5-HTP) with or without Vitamin B6 (pyridoxal phosphate) as a cofactor in combination with (−)hydroxycitric acid (HCA). This composition may be used for the treatment of obesity or appetite suppression.

Claims

12. A composition comprising:

(a) At least 0.5 mg of 5-hydroxytryptophan, and

(b) At least 0.5 mg of (−

)-hydroxycitric acid or any derivative thereof.

13. A method for the treatment of obesity or inducing weight loss in human subjects comprising administration of a composition comprising:

(a) a compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of precursors of serotonin, pro-drugs of serotonin, or an intermediate in the biosynthesis of serotonin; and

(b) a compound selected from the group consisting of (−

)-hydroxycitric acid, a pharmaceutically acceptable salt thereof or (−

)-hydroxycitric acid lactone.

14. The method according to claim 13, wherein the compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof is 5-hydroxytryptophan.

15. The method according to claim 13, wherein the compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof is naturally derived 5-hydroxytryptophan.

16. The method according to claim 13, wherein compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof is selected from the group consisting of L-tryptophan, L-5-hydroxytryptophan, diethyl N-benzyloxycarbonyl-5-benzyloxycarbonyloxy-L-tryptophyl-L-aspartate, dibenzyl N-benzyloxycarbonyl-5-hydroxy-L-tryptophanylaspartate, 5-Hydroxy-L-tryptophyl-L-aspartic acid trihydrate, diethyl N-benzyloxycarbonyl-5-hydroxy-L-tryptophyl-L-glutamate, diethyl 5-hydroxy-L-tryptophyl-L-glutamate hydrochloride, dibenzyl L-benzyloxycarbonyl-5-hydroxytryptophyl-L-glutamate, 5-hydroxy-L-tryptophyl-L-glutamic acid, pentachlorophenyl ester of N-benzyloxycarbonyl-5-hydroxy-L-tryptophan, methyl ester of N-benzyloxycarbonyl-5-hydroxyl-L-tryptophy-L-tyrosine, N-Acetyl-5-hydroxy-L-tryptophan, methyl ester of N-acetyl-5-hydroxy-L-tryptophyl-L-tyrosine, methyl ester of n-acetyl-5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan, 5-hydroxy-L-tryptophyl-L-alaninc hydrate, 5-hydroxy-L-tryptophan-L-valine, 5-hydroxy-L-tryptophyl-L-leucine, 5-hydroxy-L-tryptophyl-L-proline, 5-hydroxy-L-tryptophyl-L-phenylalanine, 5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan, 5-hydroxy-L-tryptophyl-L-tryptophan, 1-5-hydroxytryptophyl-L-serine, 5-hydroxy-L-tryptophyl-L-arginine, 5-hydroxy-L-tryptophylglycine, 5-hydroxy 1-tryptophyl-gamma-aminobutyric acid, 5-hydroxy-L-tryptophanamide hydrate, methyl ester of 5-hydroxy-L-tryptophyl-L-histidine, benzyl ester of L-5-hydroxytryptophan, benzyl ester of N-benzyloxycarbonyl-5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan, 5-Hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan hemihydrate, 5-hydroxytryptophan inosinate, theophylline salt of (DL) 5-hydroxytryptophan, and combinations thereof.

17. The composition according to claim 13, comprising between about 0.5 mg to about 5 g of 5-hydroxytryptophan.

18. The composition according to claim 13, comprising between about 0.5% to about 15% by weight 5-hyydroxytryptophan.

19. The method according to claim 13, comprising between about 0.5 mg to 10 g of (−

)-hydroxycitric acid.

20. The method according to claim 13, comprising between about 0.5% to about 30% by weight of (−

)-hydroxycitric acid.

21. The method according to claim 13, wherein the composition further comprises an effective amount of Vitamin B6.

22. The method according to claim 13, further comprising administration of an effective amount of other anorectic agents selected from the group consisting of phentermine diethylpropion, and phendimetrazine.

23. The method according to claim 13, wherein the compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.5 mg/day to about 5 g/day and a compound selected from the group consisting of (−

)-hydroxycitric acid, a pharmaceutically acceptable salt thereof or (−

)-hydroxycitric acid lactone is administered at a dose ranging from 0.5 mg to 10 g per day.

24. A method for suppressing the appetite of human subjects comprising administration of a composition comprising:

(a) a compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of precursors of serotonin, pro-drugs of serotonin, or an intermediate in the biosynthesis of serotonin; and

(b) a compound selected from the group consisting of (−

)-hydroxycitric acid, a pharmaceutically acceptable salt thereof or (−

)-hydroxycitric acid lactone.

25. The method according to claim 24, wherein the compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof is 5-hydroxytryptophan.

26. The method according to claim 24, wherein the compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof is naturally derived 5-hydroxytryptophan.

27. The method according to claim 24, wherein compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof is selected from the group consisting of L-tryptophan, L-5-hydroxytryptophan, diethyl N-benzyloxycarbonyl-5-benzyloxycarbonyloxy-L-tryptophyl-L-aspartate, dibenzyl N-benzyloxycarbonyl-5-hydroxy-L-tryptophanylaspartate, 5-Hydroxy-L-tryptophyl-L-aspartic acid trihydrate, diethyl N-benzyloxycarbonyl-5-hydroxy-L-tryptophyl-L-glutamate, diethyl 5-hydroxy-L-tryptophyl-L-glutamate hydrochloride, dibenzyl L-benzyloxycarbonyl-5-hydroxytryptophyl-L-glutamate, 5-hydroxy-L-tryptophyl-L-glutamic acid, pentachlorophenyl ester of N-benzyloxycarbonyl-5-hydroxy-L-tryptophan, methyl ester of N-benzyloxycarbonyl-5-hydroxyl-L-tryptophy-L-tyrosine, N-Acetyl-5-hydroxy-L-tryptophan, methyl ester of N-acetyl-5-hydroxy-L-tryptophyl-L-tyrosine, methyl ester of n-acetyl-5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan, 5-hydroxy-L-tryptophyl-L-alaninc hydrate, 5-hydroxy-L-tryptophan-L-valine, 5-hydroxy-L-tryptophyl-L-leucine, 5-hydroxy-L-tryptophyl-L-proline, 5-hydroxy-L-tryptophyl-L-phenylalanine, 5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan, 5-hydroxy-L-tryptophyl-L-tryptophan, 1-5-hydroxytryptophyl-L-serine, 5-hydroxy-L-tryptophyl-L-arginine, 5-hydroxy-L-tryptophylglycine, 5-hydroxy 1-tryptophyl-gamma-aminobutyric acid, 5-hydroxy-L-tryptophanamide hydrate, methyl ester of 5-hydroxy-L-tryptophyl-L-histidine, benzyl ester of L-5-hydroxytryptophan, benzyl ester of N-benzyloxycarbonyl-5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan, 5-Hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan hemihydrate, 5-hydroxytryptophan inosinate, theophylline salt of (DL) 5-hydroxytryptophan, and combinations thereof.

28. The composition according to claim 24, comprising between about 0.5 mg to about 5 g of 5-hydroxytryptophan.

29. The composition according to claim 24, comprising between about 0.5% to about 15% by weight 5-hyydroxytryptophan.

30. The method according to claim 24, comprising between about 0.5 mg to 10 g of (−

)-hydroxycitric acid.

31. The method according to claim 24, comprising between about 0.5% to about 30% by weight (−

)-hydroxycitric acid.

32. The method according to claim 24, wherein the composition further comprises an effective amount of Vitamin B6.

33. The method according to claim 24, further comprising administration of an effective amount of other anorectic agents selected from the group consisting of phentermine diethylpropion, and phendimetrazine.

34. The method according to claim 24, wherein the compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.5 mg/day to about 5 g/day and a compound selected from the group consisting of (−

)-hydroxycitric acid, a pharmaceutically acceptable salt thereof or (−

)-hydroxycitric acid lactone is administered at a dose ranging from 0.5 mg to 10 g per day.

35. A method for the reduction of body mass of human subjects comprising administration of a composition comprising:

(a) a compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of precursors of serotonin, pro-drugs of serotonin, or an intermediate in the biosynthesis of serotonin; and

(b) a compound selected from the group consisting of (−

)-hydroxycitric acid, a pharmaceutically acceptable salt thereof or (−

)-hydroxycitric acid lactone.

36. A method for the treatment of stress comprising administration of a composition comprising:

(a) a compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of precursors of serotonin, pro-drugs of serotonin, or an intermediate in the biosynthesis of serotonin; and

(b) a compound selected from the group consisting of (−

)-hydroxycitric acid, a pharmaceutically acceptable salt thereof or (−

)-hydroxycitric acid lactone.

37-1. The composition according to claim 1, comprising 5-hydroxytryptophan and (−

)-hydroxycitric acid in a ratio of 1 to 10 by weight.