Chemosensory Receptor Ligand-Based Therapies

• US 20110065660A1
• Filed: 10/19/2010
• Published: 03/17/2011
• Est. Priority Date: 04/20/2009
• Status: Active Grant

• Current Assignee: Ambra Bioscience LLC
• Original Assignee: Elcelyx Therapeutics, Inc.
• Inventors: BROWN, Martin R., JONES, Christopher R.G., BARON, Alain
• Granted Patent: US 8,828,953 B2
• Time in Patent Office: Days
• US Class Current: 514/26
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/195 having an amino group
• 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 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/235 having an aromatic ring attached to a carboxyl group
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00

Abstract

Provided herein are methods for treating diabetes, obesity, and other metabolic diseases, disorders or conditions comprising chemosensory receptor ligands. Also provided herein are chemosensory receptor ligand compositions and the preparation thereof for the methods of the present invention.

Claims

1. A composition comprising a chemosensory receptor ligand, wherein the composition is adapted to release a therapeutically effective amount of the ligand to one or more regions of the intestine of a subject.

2. A composition according to claim 1, wherein the composition further releases at least some of the chemosensory receptor ligand in the stomach.

3. A composition according to claim 1, wherein one or more regions of the intestine are the duodenum, jejunum, ileum, caecum, colon and/or rectum.

4. A composition according to claim 1, wherein one or more regions of the intestine are the jejunum, ileum, caecum, colon and/or rectum.

5. A composition according to claim 1, wherein the composition releases at an onset of about 5 to about 45 minutes, about 105 to about 135 minutes, about 165 to about 195 minutes, about 225 to about 255 minutes or a combination of times thereof following administration to a subject.

6. A composition according to claim 1, wherein the composition releases at an onset of about pH 5.0, about pH 5.5, about pH 6.0, about pH 6.5, about pH 7.0, or combination thereof following administration to a subject.

7. A composition according to claim 1, wherein the chemosensory receptor ligand is selected from the group consisting of a sweet receptor ligand, a bitter receptor ligand, an umami receptor ligand, a fat receptor ligand, and a bile acid receptor ligand.

8. A composition according to claim 7, wherein the sweet receptor ligand is selected from the group consisting of sucralose, aspartame, Stevioside, Rebaudioside A, Rebaudioside B, Rebaudioside C, Rebaudioside D, Rebaudioside E, Rebaudioside F, Neotame, acesulfame-K and saccharin.

9. A composition according to claim 7, wherein the bitter receptor ligand is selected from the group consisting of a flavanone, a flavone, a flavonol, a flavan, a phenolic flavonoid, an isoflavone, a limonoid aglycone, a glucosinolate or hydrolysis product thereof and an organic isothiocyanate.

10. A composition according to claim 7, wherein the umami receptor ligand is selected from the group consisting of glutamate salt, glutamine, acetyl glycine and aspartame.

11. A composition according to claim 7, wherein the fat receptor ligand is selected from the group consisting of a linoleic acid, an oleic acid, an omega-3 fatty acid, a palmitate, an oleoylethanolamide, a mixed fatty acid emulsion and an N-acylphosphatidylethanolamine (NAPE).

12. A composition according to claim 7, wherein the bile acid receptor ligand is selected from the group consisting of deoxycholic acid, a taurocholic acid and a chenodeoxycholic acid.

13. A composition according to any of claims 1-12, wherein the chemosensory receptor ligand is nonmetabolized.

14. A composition according to any of claims 1-12, wherein the chemosensory receptor ligand is an agonist.

15. A composition according to claim 1, wherein the chemosensory receptor ligand is an enhancer.

16. A composition comprising a nonmetabolized ligand to a sweet chemosensory receptor wherein the composition has a sweetness potency of at least about 100 times the sweetness potency of sucrose, and wherein the composition is adapted to release the ligand to one or more regions of the intestine of a subject.

17. A composition according to claim 16, wherein the composition has a sweetness potency of at least 500 times the sweetness potency of sucrose.

18. A composition according to claim 16, wherein the composition has a sweetness potency of at least 1000 times the sweetness potency of sucrose.

19. A composition according to claim 16 further comprising a chemosensory receptor ligand selected from the group consisting of a sweet receptor ligand, a bitter receptor ligand, an umami receptor ligand, a fat receptor ligand, and a bile acid receptor ligand.

20. A composition comprising a nonmetabolized ligand to a sweet chemosensory receptor wherein the composition has a sweetness potency equivalent to at least about 500 grams of sucrose, and wherein the composition is adapted to release the ligand to one or more regions of the intestine of a subject.

21. A composition according to claim 20, wherein the composition has a sweetness potency equivalent to at least about 5000 grams of sucrose.

22. A composition according to claim 20, wherein the composition has a sweetness potency equivalent to at least about 10000 grams of sucrose.

23. A composition according to claim 20 further comprising a chemosensory receptor ligand selected from the group consisting of a sweet receptor ligand, a bitter receptor ligand, an umami receptor ligand, a fat receptor ligand, and a bile acid receptor ligand.

24. A method of treating a condition associated with a chemosensory receptor in a subject comprising administering at a composition comprising a chemosensory receptor ligand, wherein the composition is adapted to release a therapeutically effective amount of the ligand to one or more regions of the intestine of a subject.

25. A method according to claim 24, wherein the composition further releases at least some of the chemosensory receptor ligand in the stomach.

26. A method according to claim 24, wherein one or more regions of the intestine are the duodenum, jejunum, ileum, caecum, colon and/or rectum.

27. A method according to claim 24, wherein one or more regions of the intestine are the jejunum, ileum, caecum, colon and/or rectum.

28. A method according to claim 24, wherein the composition releases at an onset of about 5 to about 45 minutes, about 105 to about 135 minutes, about 165 to about 195 minutes, about 225 to about 255 minutes or a combination of times thereof following administration to a subject.

29. A method according to claim 24, wherein the composition releases at an onset of about pH 5.0, about pH 5.5, about pH 6.0, about pH 6.5, about pH 7.0, or combination thereof following administration to a subject.

30. A method according to claim 24, wherein the chemosensory receptor ligand is selected from the group consisting of a sweet receptor ligand, a bitter receptor ligand, an umami receptor ligand, a fat receptor ligand, and a bile acid receptor ligand.

31. A method according to claim 30, wherein the sweet receptor ligand is selected from the group consisting of sucralose, aspartame, Stevioside, Rebaudioside A, Rebaudioside B, Rebaudioside C, Rebaudioside D, Rebaudioside E, Rebaudioside F, Neotame, acesulfame-K and saccharin.

32. A method according to claim 30, wherein the bitter receptor ligand is selected from the group consisting of a flavanone, a flavone, a flavonol, a flavan, a phenolic flavonoid, an isoflavone, a limonoid aglycone, a glucosinolate or hydrolysis product thereof and an organic isothiocyanate.

33. A method according to claim 30, wherein the umami receptor ligand is selected from the group consisting of glutamate salt, glutamine, acetyl glycine and aspartame.

34. A method according to claim 30, wherein the fat receptor ligand is selected from the group consisting of a linoleic acid, an oleic acid, an omega-3 fatty acid, a palmitate, an oleoylethanolamide, a mixed fatty acid emulsion and an N-acylphosphatidylethanolamine (NAPE).

35. A method according to claim 30, wherein the bile acid receptor ligand is selected from the group consisting of deoxycholic acid, a taurocholic acid and a chenodeoxycholic acid.

36. A method according to any of claims 24-35, wherein the chemosensory receptor ligand is an agonist.

37. A method according to any of claims 24-35, wherein the chemosensory receptor ligand is nonmetabolized.

38. A method according to claim 24, wherein the chemosensory receptor ligand is an enhancer.

39. A method according to claim 24, wherein the composition is administered prior to ingestion of food by the subject.

40. A method according to claim 24, wherein the condition associated with a chemosensory receptor is selected from metabolic syndrome, insulin resistance, diabetes type I, diabetes type II, obesity, binge eating, undesired food cravings, food addiction, a desire to reduce food intake or to lose weight or maintain weight loss, anorexia, glucose intolerance, gestational diabetes mellitus (GDM), dyslipidemia, post-prandial dyslipidemia, bone loss disorders, osteopenia, osteoporosis, muscle wasting disease, muscle degenerative disorders, polycystic ovary syndrome (PCOS), non-alcoholic fatty liver disease (NAFL), non-alcoholic steatohepatitis (NASH), depression, a mood disorder, immune disorders of the gut, celiac disease, bowel irregularity, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), ulcerative colitis, Crohn'"'"'s disease, and short bowel syndrome.

41. A method according to claim 24, wherein the condition is diabetes.

42. A method according to claim 24, wherein the condition is obesity.

43. A method according to claim 24, wherein the subject is undergoing bariatric surgery.

44. A method according to claim 24 further comprising administration of a drug for diabetes or obesity.

45. A method of treating a disease, disorder or defect in energy homeostasis in a subject comprising administering at a composition comprising a chemosensory receptor ligand, wherein the composition is adapted to release a therapeutically effective amount of the ligand to one or more regions of the intestine of a subject.