Pharmaceutical compositions including ACE/NEP inhibitors and bioavailability enhancers

• US 6,890,918 B2
• Filed: 04/30/2002
• Issued: 05/10/2005
• Est. Priority Date: 04/30/2001
• Status: Expired due to Fees

• Current Assignee: Supernus Pharmaceuticals Incorporated
• Original Assignee: Shire Laboratories, Inc. (Supernus Pharmaceuticals Incorporated)
• Inventors: Shojaei, Amir, Chang, Rong-Kun, Burnside, Beth
• Primary Examiner(s): Henley, III, Raymond J.
• Application Number:
  US10/134,651
• Publication Number:
  US 20030096761A1
• Time in Patent Office: 1,106 Days
• Field of Search: 514/474, 514/562, 514/574, 514/211.05, 514/466
• US Class Current: 514/211.05
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• 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 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/28 Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

A pharmaceutical composition comprising an inhibitor of angiotensin converting enzyme and neutral endopeptidase, such as sampatrilat, and at least one bioavailability enhancer such as an organic acid, e.g., ascorbic acid. Such a composition has improved systemic bioavailability.

Claims

1. A pharmaceutical composition comprising at least one dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, and at least one bioavailability enhancer selected from ascorbic acid, citric acid, malic acid, fumaric acid, and pharmaceutically acceptable salts of said acids.

2. The pharmaceutical composition according to claim 1, wherein said at least one dual inhibitor is chosen from among sampatrilat, fasidotril, and omapatrilat.

3. The pharmaceutical composition according to claim 1, which comprises sampatrilat as the only dual inhibitor.

4. The pharmaceutical composition according to claim 1, wherein the bioavailability enhancer is ascorbic acid.

5. The pharmaceutical composition according to claim 1, which contains at least 0.5 wt. % of at least one dual inhibitor, and at least 1 wt. % of at least one enhancer.

6. The pharmaceutical composition according to claim 1, wherein said dual inhibitor(s) is present in an amount of from about 0.5 wt. % to about 50 wt. %.

7. The pharmaceutical composition according to claim 6, wherein said dual inhibitor is present in an amount of from about 1 wt. % to about 26 wt. %.

8. The pharmaceutical composition according to claim 1, wherein said bioavailability enhancer(s) is present in an amount of from about 1 wt. % to about 75 wt %.

9. The pharmaceutical composition according to claim 8, wherein said bioavailability enhancer(s) in an amount of from about 5 wt. % to about 40 wt. %.

10. The pharmaceutical composition according to claim 3, wherein said dual inhibitor is present in an amount of from 0.5 wt. % to about 50 wt. %.

11. The pharmaceutical composition according to claim 10, wherein said dual inhibitor is present in an amount of from about 1 wt. % to about 25 wt. %.

12. The pharmaceutical composition according to claim 4, wherein the ascorbic acid is present in an amount of from about 1 wt. % to about 75 wt. %.

13. The pharmaceutical composition according to claim 12, wherein the ascorbic acid is present in an amount of from about 5 wt. % to about 40 wt. %.

14. The pharmaceutical composition according to claim 3, wherein the bioavailability enhancer is ascorbic acid.

15. A method for treating a cardiovascular disorder in a patient, comprising administering to said patient a pharmaceutically effective amount of a composition according to claim 1.

16. The method of claim 15, wherein said composition is comprised of sampatrilat and ascorbic acid.

17. A process for preparing a pharmaceutical composition, comprising combining at least one agent, in powder form, selected from the group consisting of dual inhibitors of angiotensin convening enzyme and neutral endopeptidase, with at least one bioavailability enhancer selected from ascorbic acid, citric acid, malic acid, fumaric acid, and pharmaceutically acceptable salts of said acids, also in powder form to obtain a powdered mixture and either (a) encapsulating said powdered mixture in a capsule or (b) forming said powdered mixture into a tablet.

18. The process of claim 17, wherein the composition is comprised of sampatrilat and ascorbic acid.