Patent EA-004064-B1 (EA)
Title: Combination therapy of angiotensin converting enzyme inhibitor and epoxy-steroidal aldosterone antagonist for treatment of cardiovascular disease
Inventor: ALEXANDER JOHN C
IPC: A61P9/00
Filed: 2000-03-03
Abstract: 1. A combination comprising a therapeutically effective amount of an epoxy-steroidal aldosterone receptor antagonist and an angiotensin converting enzyme inhibitor, wherein said angiotensin converting enzyme inhibitor is selected from the group consisting of alacepril, benazepril, captopril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, fosinoprilat, imidapril, lisinopril, perindopril, quinapril, ramipril, saralasin acetate, temocapril, trandolapril, ceranapril, moexipril, quinaprilat, spirapril, Bioproject BP1.137, Chiesi CHF 1514, Fisons FPL-66564, idrapril, Marion Merrell Dow MDL-100240, perindoprilat, and Servier S-5590. 2. A combination of Claim 1, wherein said epoxy-steroidal aldosterone receptor antagonist being present in an amount which is therapeutically effective to antagonize aldosterone but which amount is not sufficient for said aldosterone receptor antagonist to induce a substantially adverse side effect. 3. The combination of Claim 1, wherein angiotensin converting enzyme inhibitor is selected from the group consisting of alacepril, benazepril, captopril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, fosinoprilat, imidapril, lisinopril, perindopril, quinapril, ramipril, saralasin acetate, temocapril, trandolapril, ceranapril, moexipril, quinaprilat, spirapril. 4. The combination of Claim 1, wherein said aldosterone receptor antagonist is an epoxy-steroidal type compound characterized in having a 9alpha-, 11alpha-substituted epoxy moiety. 5. The combination of Claim 4, wherein said epoxy-steroidal type compound is eplerenone. 6. The combination of Claim 1 further characterized by said angiotensin converting enzyme inhibitor and said aldosterone receptor antagonist being present in said combination in a weight ratio range from about 0.5-to-one to about twenty-to-one of said angiotensin converting enzyme inhibitor to said aldosterone receptor antagonist. 7. The combination of Claim 6, wherein said weight ratio range is from about one-to-one to about fifteen-to-one. 8. The combination of Claim 7, wherein said weight ratio range is from about one-to-one to about five-to-one. 9. A combination therapy for treating cardiovascular disorders in a subject afflicted with or susceptible to multiple cardiovascular disorders, wherein said combination therapy comprises administering a therapeutically effective amount of a two-component combination consisting essentially of an epoxy-steroidal aldosterone receptor antagonist as a first component and angiotensin converting enzyme inhibitor as a second component, wherein said angiotensin converting enzyme inhibitor is selected from the group consisting of alacepril, benazepril, captopril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, fosinoprilat, imidapril, lisinopril, perindopril, quinapril, ramipril, saralasin acetate, temocapril, trandolapril, ceranapril, moexipril, quinaprilat, spirapril, BioprojectBP1.137, Chiesi CHF 1514, Fisons FPL-66564, idrapril, Marion Merrell Dow MDL-100240, perindoprilat, and Servier S-5590. 10. The combination therapy of Claim 9, wherein said epoxy-steroidal aldosterone receptor antagonist being present in an amount therapeutically effective to antagonize aldosterone but insufficient to induce an adverse side effect. 11. The combination therapy of Claim 9, wherein said angiotensin converting enzyme inhibitor is selected from the group consisting of alacepril, benazepril, captopril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, fosinoprilat, imidapril, lisinopril, perindopril, quinapril, ramipril, saralasin acetate, temocapril, trandolapril, ceranapril, moexipril, quinaprilat, spirapril. 12. The combination therapy of Claim 9 characterized by administering said angiotensin converting enzyme inhibitor and said epoxy-steroidal aldosterone receptor antagonist in a consecutive manner. 13. The combination therapy of Claim 9 characterized by administering said angiotensin converting enzyme inhibitor and said epoxy-steroidal aldosterone receptor antagonist in a substantially simultaneous manner. 14. The combination of Claim 9, wherein said epoxy-steroidal aldosterone receptor antagonist is compound characterized in having a 9alpha-, 11alpha-substituted epoxy moiety. 15. The combination therapy of Claim 14, wherein said epoxy-steroidal compound is eplerenone. 16. The combination therapy of Claim 9 characterized by said angiotensin converting enzyme inhibitor and said epoxy-steroidal aldosterone receptor antagonist being used in said co-therapy in a weight ratio range from about 0.5-to-one to about twenty-to-one of said angiotensin converting enzyme inhibitor to said aldosterone receptor antagonist. 17. The combination therapy of Claim 16, wherein said weight ratio range is from about one-to-one to about fifteen-to-one. 18. The combination therapy of Claim 17, wherein said weight ratio range is from about one-to-one to about five-to-one. 19. The combination therapy of Claim 9, wherein said angiotensin converting enzyme inhibitor is captopril, in a dose range from about 40 mg to about 80 mg per dose, or is enalapril in a dose range from about 5 mg to about 25 mg per dose. 20. The combination therapy of Claim 9, wherein said angiotensin converting enzyme inhibitor is ramipril, in a dose range from about 2 mg to about 20 mg per dose, or is lisinopril in a dose range from about 5 mg to about 25 mg per dose. 21. The combination therapy of Claims 9, 19 or 20, wherein said epoxy-steroidal aldosterone receptor antagonist is eplerenone in a dose range from about 25 mg to about 100 mg per dose.