Chemosensory Receptor Ligand-Based Therapies

• US 20140030332A1
• Filed: 01/06/2012
• Published: 01/30/2014
• Est. Priority Date: 01/07/2011
• Status: Active Grant

• Current Assignee: Anji Pharmaceuticals, Inc.
• Original Assignee: Elcelyx Therapeutics, Inc.
• Inventors: Baron, Alain D., Brown, Martin R., Jones, Christopher R.G., Beeley, Nigel R.A., Fineman, Mark S.
• Granted Patent: US 9,050,292 B2
• Time in Patent Office: Days
• US Class Current: 424/474
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• 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 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• 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: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administrating a composition comprising a chemosensory receptor ligand, such as a bitter receptor ligand. Also provided herein are chemosensory receptor ligand compositions, including bitter receptor ligand compositions, and methods for the preparation thereof for use in the methods of the present invention. Also provided herein are compositions comprising metformin and salts thereof and methods of use.

Claims

1-201. -201. (canceled)

202. A method of lowering blood glucose levels in a subject in need thereof, comprising administering a composition comprising metformin or salt thereof, wherein the composition is adapted to release a therapeutically effective amount of the metformin or salt thereof to one or more regions of the intestine.

206. The method according to any one of claims 202-205, wherein said metformin salt is metformin hydrochloride.

207. The method according to any one of claims 202-205, wherein said one or more regions of the intestine are the duodenum, jejunum, ileum and/or lower intestine.

208. The method according to any one of claims 202-205, wherein said one or more regions of the intestine are the jejunum, ileum and/or lower intestine.

209. The method according to any one of claims 202-205, wherein said composition releases the metformin or salt thereof 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.

210. The method according to any one of claims 202-205, wherein the therapeutically effective amount of metformin or salt thereof is about 1 mg to about 2000 mg.

211. The method according to any one of claims 202-205, wherein the therapeutically effective amount of metformin or salt thereof is about 50 mg to about 1000 mg.

212. The method according to any one of claims 202-205, wherein the average bioavailaility of the metformin or salt thereof is less than the average bioavailability of an immediate release metformin formulation having an equivalent amount of metformin.

213. The method according to any one of claims 202-205, wherein said icomposition further comprises an antidiabetic or antiobesity agent.

214. The method according to claim 213, wherein said antidiabetic agent is selected from the group consisting of thiazolidinediones, sulfonyureas, meglitinides, alpha-glucosidase inhibitors, DPP-IV inhibitors, and incretin mimetics.

215. The method according to claim 213, wherein the antiobesity agent is selected from the group consisting of phentermine, fenfluramine, sibutramine, rimonabant, topiramate, zonisamide bupropion, naltrexone, lorcaserin, and orlistat.

216. The method according to any one of claims 202-205, the composition 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, a sour receptor ligand and a bile acid receptor ligand.

218. The method according to claim 202, 213 or 214, wherein said condition is diabetes or pre-diabetes.

219. The method according to claim 202, 213 or 215, wherein said condition is obesity.

203. A method of treating disorders of glucose metabolism in a subject in need thereof, comprising administering a composition comprising metformin or a salt thereof, wherein the composition is adapted to release a therapeutically effective amount of the metformin or salt thereof to one or more regions of the intestine.

204. The method according to claim 203, wherein said disorder is hyperglycemia.

205. A method of treating a condition associated with a chemosensory receptor in a subject in need thereof comprising administering a composition comprising metformin or a salt thereof, wherein the composition is adapted to release a therapeutically effective amount of the metformin or salt thereof to one or more regions of the intestine.

217. The method according to claim 205 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, desire to maintain healthy weight, desire to maintain normal blood glucose metabolism, anorexia, pre-diabetes, glucose intolerance, gestational diabetes mellitus (GDM), impaired fasting glycemia (IFG), post-prandial hyperglycemia, accelerated gastric emptying, dumping syndrome, delayed gastric emptying, dyslipidemia, post-prandial dyslipidemia, hyperlipidemia, hypertriglyceridemia, post-prandial hypertriglyceridemia, insulin resistance, 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), immune disorders of the gut, celiac disease, bowel irregularity, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), ulcerative colitis, Crohn'"'"'s disease, short bowel syndrome, peripheral neuropathy and diabetic neuropathy.

220. A method of treating a disease, disorder or defect in energy homeostasis in a subject comprising administering a composition comprising metformin or a salt thereof, wherein the composition is adapted to release a therapeutically effective amount of the metformin or salt thereof to one or more regions of the intestine.

221. A pharmaceutical composition comprising metformin or a salt thereof and another antidiabetic or antiobesity agent, wherein the average bioavailability of the metformin is less than the average bioavailability of an immediate release metformin formulation having an equivalent amount of metformin.

222. The pharmaceutical composition according to claim 221, wherein the metformin or salt thereof is enterically-coated.

223. The pharmaceutical composition according to claim 222, wherein the metformin or salt thereof is released from said pharmaceutical dosage form 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 a combination thereof following administration to a subject.

224. The pharmaceutical composition according to claim 221, wherein said antidiabetic agent is selected from the group consisting of thiazolidinediones, sulfonyureas, meglitinides, alpha-glucosidase inhibitors, DPP-IV inhibitors, and incretin mimetics.

225. The pharmaceutical composition according to claim 221, wherein the antiobesity agent is selected from the group consisting of phentermine, fenfluramine, sibutramine, rimonabant, topiramate, zonisamide bupropion, naltrexone, lorcaserin, and orlistat.

226. The pharmaceutical composition according to claim 221, 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, a sour receptor ligand and a bile acid receptor ligand.