Chemosensory Receptor Ligand-Based Therapies

• US 20100267643A1
• Filed: 04/20/2010
• Published: 10/21/2010
• 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 9,901,551 B2
• Time in Patent Office: Days
• US Class Current: N/A
• 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 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/195 having an amino group
• 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 31/235 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 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• 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 38/26 Glucagons
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• 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 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin

Abstract

Provided herein are compositions and methods for treating diabetes, obesity, and other metabolic diseases, disorders or conditions with chemosensory receptor ligands. Also provided herein are pharmaceutical compositions useful for the methods of the present invention.

Claims

1. A method of treating a condition associated with a chemosensory receptor in a subject comprising administering at least one chemosensory receptor ligand to the subject.

2. The method of claim 1, wherein at least one chemosensory receptor ligand is non-metabolizable.

3. The method of claim 1, wherein at least one chemosensory receptor ligand is selected from a sweet receptor ligand, a bitter receptor ligand, an umami receptor ligand, a fat receptor ligand, a bile acid receptor ligand, or any combination thereof.

4. The method of claim 3, wherein a sweet receptor ligand is selected from a glucose, sucralose, aspartame, Stevioside, Rebaudioside, Neotame, acesulfame-K, or saccharin.

5. The method of claim 3, wherein a bitter receptor ligand is selected from a flavanone, a flavone, a flavonol, a flavan, a phenolic flavonoid, an isoflavone, a limonoid aglycone, a glucosinolate or hydrolysis product thereof, or an isothiocyanate.

6. The method of claim 3, wherein an umami receptor ligand is selected from a glutamate salt, glutamine, acetyl glycine, or aspartame.

7. The method of claim 3, wherein the fat receptor ligand is selected from a linoleic acid, an oleic acid, a palmitate, an oleoylethanolamide, a mixed fatty acid emulsion, or an N-acylphosphatidylethanolamine (NAPE).

8. The method of claim 3, wherein the bile acid is selected from a deoxycholic acid, a taurocholic acid or a chenodeoxycholic acid.

9. The method of claim 1, further comprising the administration of at least one chemosensory receptor metabolite that corresponds to at least one chemosensory receptor ligand.

10. The method of claim 1, wherein at least one chemosensory receptor ligand is co-administered with the ingestion of food by the subject.

11. The method of claim 1, wherein the composition is administered to the upper intestine, the lower intestine, or both.

12. The method of claim 1, wherein the composition is administered to the duodenum, jejunum, ileum, colon or combination thereof.

13. The method of claim 1, wherein the composition releases at about 15 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 thereof following administration to a subject.

14. The method of claim 1, wherein the composition releases at about pH 5.5, about pH 6.0, about pH 6.5, about pH 7.0, or combination thereof following administration to a subject.

15. The method of claim 1, wherein the chemosensory receptor ligand modulates the hormonal profile of lower intestine and the hormonal profile comprises GLP-1, Oxyntomodulin, and Peptide YY.

16. The method of claim 1, wherein the chemosensory receptor ligand modulates the hormonal profile of the upper intestine and the hormonal profile comprises GLP-1, GLP-2, Oxyntomodulin, Peptide YY, GIP, Insulin C Peptide, glucagon, insulin, CCK, or any combination thereof.

17. The method of claim 1, wherein the chemosensory receptor ligand sensitizes lower intestinal chemosensory receptors by stimulating chemosensory receptors in the upper intestine.

18. The method of claim 1, wherein the condition associated with a chemosensory receptor is selected from metabolic syndrome, 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 (e.g., celiac disease), bowel irregularity, irritable bowel syndrome (IBS), or inflammatory bowel disease (IBD), including, e.g., ulcerative colitis, Crohn'"'"'s disease, and short bowel syndrome.

19. A composition comprising at least one chemosensory receptor ligand whereby the composition is effective for treating a condition associated with a chemosensory receptor.

20. The composition of claim 19, wherein the composition is formulated for release in the lower intestine, upper intestine, or both and whereby the composition is effective for treating a condition associated with a chemosensory receptor.

21. The composition of claim 19, wherein the composition is formulated for release in the duodenum, jejunum, ileum, colon, or a combination thereof and whereby the composition is effective for treating a condition associated with a chemosensory receptor.

22. The composition of claim 19, wherein the composition is formulated for release at about 15 to about 45 minutes, about 105 to about 135 minutes, about 165 to about 195 minutes, about 225 to about 255 minutes or combination of times thereof following administration and whereby the composition is effective for treating a condition associated with a chemosensory receptor.

23. The composition of claim 19, wherein the composition is formulated for release at about pH 5.5, about pH 6.0, about pH 6.5, about pH 7.0, or a combination thereof following administration and whereby the composition is effective for treating a condition associated with a chemosensory receptor.

24. The composition of claim 19, wherein the condition associated with a chemosensory receptor is selected from metabolic syndrome, 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 (e.g., celiac disease), bowel irregularity, irritable bowel syndrome (IBS), or inflammatory bowel disease (IBD), including, e.g., ulcerative colitis, Crohn'"'"'s disease, and short bowel syndrome.