Method for treating severe heart failure and medicament therefor

• US 20050187210A1
• Filed: 02/23/2004
• Published: 08/25/2005
• Est. Priority Date: 02/24/2003
• Status: Active Grant

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Inventors: Sato, Osamu, Yamamura, Yoshitaka, Ozaki, Atsushi, Maki, Yosuke
• Granted Patent: US 7,423,032 B2
• Time in Patent Office: Days
• US Class Current: 514/217.10
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A method for treating severe heart failure, comprising administering to a patient an effective amount of a benzazepine compound (1): wherein R₁ is H or halogen, R₂ is OH, or —NR₅R₆ (R₅ and R₆ are H or lower alkyl, R₃ is H, halogen, lower alkyl, or lower alkoxy, R₄ is halogen, lower alkyl or lower alkoxy, or a salt thereof, and a pharmaceutical composition containing the benzazepine compound (1) or a salt thereof and use of the compound (1) or a salt thereof for preparing a medicament for treatment of severe heart failure.

Claims

1. A method for treating severe heart failure, comprising administering to a patient in need thereof a therapeutically effective amount of a benzazepine compound of the formula (1):

2. The method for treating severe heart failure according to claim 1, wherein the daily dose of the active compound is in the range of less than 0.6 mg/kg.

3. The method for treating severe heart failure according to claim 1, wherein the daily dose of the active compound is in the range from 0.1 mg/kg to less than 0.6 mg/kg.

4. The method for treating severe heart failure according to claim 1, wherein the dose of the active compound is in the range of 15 to 45 mg/body per day.

5. The method for treating severe heart failure according to claim 1, wherein the active compound is 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine or a pharmaceutically acceptable salt thereof.

6. The method for treating severe heart failure according to claim 1, wherein the active compound is 5-hydroxy-7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine or a pharmaceutically acceptable salt thereof.

7. The method for treating severe heart failure according to any one of claim 1 to 6, wherein the severe heart failure is acute heart failure or a chronic heart failure in acute exacerbation.

8. The method for treating severe heart failure according to any one of claim 1 to 6, wherein the severe heart failure is a severe heart failure of New York Heart Association Class:

III and IV.

9. A medicament for the treatment of severe heart failure which comprises as an active ingredient a benzazepine compound of the formula (1):

10. The medicament according to claim 9, wherein the active compound (1) is 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine or a pharmaceutically acceptable salt thereof.

11. The medicament according to claim 9, wherein the active compound (1) is 5-hydroxy-7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition suitable for the treatment of severe heart failure, which comprises as an active ingredient a benzazepine compound of the formula (1):

13. The pharmaceutical composition according to claim 12, wherein the active compound (1) is 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine or a pharmaceutically acceptable salt thereof.

14. The pharmaceutical composition according to claim 12, wherein the active compound (1) is 5-hydroxy-7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine or a pharmaceutically acceptable salt thereof.

15. The pharmaceutical composition according to any one of claims 12 to 14, wherein the active compound (1) or a pharmaceutically acceptable salt thereof is contained in an amount of 1 to 70% by weight based on the weight of the composition.

16. A use of a benzazepine compound of the formula (1):

17. The use of a benzazepine compound (1) or a pharmaceutically acceptable salt thereof according to claim 16, wherein the active compound (1) is 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine or a pharmaceutically acceptable salt thereof.

18. The use of a benzazepine compound (1) or a pharmaceutically acceptable salt thereof according to claim 16, wherein the active compound (1) is 5-hydroxy-7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine or a pharmaceutically acceptable salt thereof.

19. The use of a benzazepine compound (1) or a pharmaceutically acceptable salt thereof according to any one of claims 16 to 18, wherein the active compound (1) or a pharmaceutically acceptable salt thereof is contained in the medicament in a daily dosage unit of the range of less than 0.6 mg/kg.