Combination therapy for the treatment of diabetes

Patent metadata

Field	Value
Publication number	US-11576894-B2
Application number	US-201715413480-A
Country	US
Kind code	B2
Filing date	Jan 24, 2017
Priority date	Jul 8, 2009
Publication date	Feb 14, 2023
Grant date	Feb 14, 2023

Abstract

The present invention is directed to co-therapy and methods for the treatment and prevention of glucose-related disorders such as Type 2 diabetes mellitus and Syndrome X. The present invention is further directed to pharmaceutical compositions for the co-therapy and methods described herein.

First claim

What is claimed is:

1. A pharmaceutical composition comprising
(a) metformin or a pharmaceutically acceptable salt thereof in an amount in the range of from about 500 mg to about 2000 mg; and
(b) a compound of formula (I)

wherein
Ring A is

wherein R 1a is a halogen atom, a lower alkyl group, or a lower alkoxy group, and R 2a and R 3a are hydrogen atoms;
and Ring B is

wherein R 4a is a phenyl group optionally substituted by a substituent selected from the group consisting of a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a mono- or di-lower alkylamino group, a carbamoyl group, and a mono- or di-lower alkylcarbamoyl group; or a heterocyclyl group optionally substituted by a halogen atom, a cyano group, a lower alkyl group, a lower alkoxy group, a carbamoyl group, or a mono- or di-lower alkylcarbamoyl group, and Rya is a hydrogen atom; and
Y is —CH 2 —,
or a pharmaceutically acceptable salt thereof; in an amount of from about 10 mg to about 300 mg; and
between about 5% and about 50% by weight of diluent which is microcrystalline cellulose;
between about 1% and about 10% by weight of binder comprising a material selected from the group consisting of polyvinylpyrrolidone, methylcellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose; and
between about 1% and about 10% by weight of disintegrant which is croscarmellose sodium.

2. The pharmaceutical composition as in claim 1 , wherein the metformin or pharmaceutically acceptable salt thereof is metformin hydrochloride.

3. A pharmaceutical composition comprising
(a) metformin hydrochloride in an amount in the range of from about 100 mg to about 2000 mg;
(b) a compound of formula (I-X)

or a pharmaceutically acceptable salt thereof in an amount in the range of from about 50 mg to about 500 mg; and
(c) between about 5% and about 50% by weight of diluent which is microcrystalline cellulose;
(d) between about 1% and about 10% by weight of binder comprising a material selected from the group consisting of polyvinylpyrrolidone, methylcellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose, and
(e) between about 1% and about 10% by weight of disintegrant which is croscarmellose sodium.

4. The pharmaceutical composition as in claim 3 , wherein the metformin hydrochloride is present in an amount of about 250 mg, about 500 mg, about 750 mg, about 850 mg, or about 1000 mg; and wherein the compound of formula (I-X) or pharmaceutically acceptable salt thereof is present in an amount of about 50 mg, about 100 mg, about 150 mg or about 300 mg.

5. The pharmaceutical composition as in claim 3 , wherein the compound of formula (I-X) is a crystalline hemihydrate.

6. The pharmaceutical composition as in claim 3 , wherein the metformin hydrochloride is present in an amount of about 500 mg and wherein the compound of formula (I-X) or pharmaceutically acceptable salt thereof is present in an amount of about 50 mg.

7. The pharmaceutical composition as in claim 3 , wherein the metformin hydrochloride is present in an amount of about 1000 mg and wherein the compound of formula (I-X) or pharmaceutically acceptable salt thereof is present in an amount of about 50 mg.

8. The pharmaceutical composition as in claim 3 , wherein the metformin hydrochloride is present in an amount of about 500 mg and wherein the compound of formula (I-X) or pharmaceutically acceptable salt thereof is present in an amount of about 150 mg.

9. The pharmaceutical composition as in claim 3 , wherein the metformin hydrochloride is present in an amount of about 1000 mg and wherein the compound of formula (I-X) or pharmaceutically acceptable salt thereof is present in an amount of about 150 mg.

10. The pharmaceutical composition as in claim 3 , wherein the metformin hydrochloride is present in an amount of about 850 mg and wherein the compound of formula (I-X) or pharmaceutically acceptable salt thereof is present in an amount of about 50 mg.

11. The pharmaceutical composition as in claim 3 , wherein the metformin hydrochloride is present in an amount of about 850 mg and wherein the compound of formula (I-X) or pharmaceutically acceptable salt thereof is present in an amount of about 50 mg.

12. The pharmaceutical composition as in claim 3 , further comprising between about 0.1% and about 2% by weight of a lubricant.

Assignees

• Janssen Pharmaceutica Nv
• Janssen Pharmaceutica Nv

Inventors

• Liang Yin
• Ryan John
• Woldu Abraham B
• Wu Lisa

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61K31/155

  Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2) · CPC title

• A61K31/381 Primary

  having five-membered rings · CPC title

• A61K2121/00

  Preparations for use in therapy · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title