Chemosensory Receptor Ligand-Based Therapies

• US 20120177730A1
• Filed: 01/06/2012
• Published: 07/12/2012
• Est. Priority Date: 01/07/2011
• Status: Abandoned Application

• Current Assignee: Anji Pharma (US) LLC
• Original Assignee: Elcelyx Therapeutics, Inc.
• Inventors: BARON, Alain D., BROWN, Martin R., JONES, Christopher R.G., BEELEY, Nigel R.A., FINEMAN, Mark S.
• Application Number:
  US13/345,135
• Publication Number:
  US 20120177730A1
• Time in Patent Office: Days
• US Class Current: 424/452
• 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. A pharmaceutical dosage form comprising:

(a) a pH 6.5 enterically coated immediate release component comprising metformin hydrochloride and a pharmaceutically acceptable excipient; and

b) a pH 6.5 enterically coated extended release component comprising metformin hydrochloride and a pharmaceutically acceptable excipient; and

wherein the combined amount of metformin from both components is less than 400 mg and wherein the metformin has sub-therapeutic plasma AUC and sub-therapeutic plasma Cmax.

2. A pharmaceutical dosage form according to claim 1, wherein the proportion of metformin hydrochloride in the immediate release component to the metformin hydrochloride in the extended release component is about 20/80, 30/70, 35/65, 40/60, 45/55 or 50/50.

3. A pharmaceutical dosage form according to claim 1, wherein the dosage form exhibits a dissolution release profile of 20-50% amount of metformin hydrochloride in about 30 to about 60 minutes after oral administration and 80-100% amount of metformin hydrochloride after 60 minutes after oral administration.

4. A pharmaceutical dosage form according to claim 1, wherein the sub-therapeutic plasma AUC and sub-therapeutic plasma Cmax resulting from administration of the dosage form is 50% or less than the plasma AUC and Cmax resulting from administration of a single dose of GLUMETZA 500 mg.

5. A pharmaceutical dosage form according to claim 1, wherein the dosage form further comprises a DPP-IV inhibitor in (a), (b) or both.

6. A pharmaceutical dosage form according to claim 1, wherein the dosage form further comprises an antidiabetic or antiobesity agent.

7. A pharmaceutical dosage form according to claim 1, wherein the dosage form further comprises (c) an immediate release component comprising metformin hydrochloride.

8. A pharmaceutical dosage form according to claim 7, wherein the (c) immediate release component has a pH 5.0 enteric coating.

9. A pharmaceutical dosage form according to claim 7, wherein the combined amount of metformin from components (a)-(c) is less than 600 mg.

10. A pharmaceutical dosage form according to claim 1, wherein the excipient in the extended release component is selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, xanthan gum, sodium alginate, polysorbate-80 and mixtures thereof.

11. A pharmaceutical dosage form according to claim 1, wherein the combined amount of metformin hydrochloride is about 250 mg.

12. A pharmaceutical dosage form according to claim 1, wherein the dosage form is a bi-layer tablet.

13. A pharmaceutical dosage form according to claim 1, wherein the dosage form is a capsule with the two components as encapsulated mini-tablets.

14. A pharmaceutical dosage form comprising

(a) a pH 6.5 enterically coated immediate release component comprising metformin hydrochloride and a pharmaceutically acceptable excipient;

and

b) a pH 6.5 enterically coated extended release component comprising metformin hydrochloride and a pharmaceutically acceptable excipient; and

wherein the metformin hydrochloride has reduced average bioavailability.

15. A pharmaceutical dosage form according to claim 14, wherein the average bioavailability is less than the average bioavailability of an immediate release metformin formulation having an equivalent amount of metformin.

16. A pharmaceutical dosage form according to claim 14, wherein the average bioavailability is less than 15%.

17. A pharmaceutical dosage form according to claim 14, wherein the proportion of metformin hydrochloride in the immediate release component to the metformin hydrochloride in the extended release component is about 20/80, 30/70, 35/65, 40/60, 45/55 or 50/50.

18. A pharmaceutical dosage form according to claim 14, wherein the dosage form further comprises a DPP-IV inhibitor in (a), (b) or both.

19. A pharmaceutical dosage form according to claim 14, wherein the dosage form further comprises (c) an immediate release component comprising metformin hydrochloride.

20. A pharmaceutical dosage form according to claim 14, wherein the (c) immediate release component has a pH 5.0 enteric coating.

21. A pharmaceutical dosage form according to claim 14, wherein the excipient in the extended release component is selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, xanthan gum, sodium alginate, polysorbate-80 and mixtures thereof.

22. A pharmaceutical dosage form according to claim 14, wherein the combined amount of metformin hydrochloride is less than 400 mg.

23. A pharmaceutical dosage form according to claim 14, wherein the combined amount of metformin hydrochloride is about 250 mg.