Compositions comprising nebivolol

• US 20050272810A1
• Filed: 05/31/2005
• Published: 12/08/2005
• Est. Priority Date: 06/04/2004
• Status: Active Grant

• Current Assignee: Mylan Laboratories Incorporated (Pfizer Inc.)
• Original Assignee: Forest Laboratories Holdings Limited (Abbvie Incorporated)
• Inventors: Davis, Eric, Bottini, Peter, O'Donnell, John
• Granted Patent: US 7,803,838 B2
• Time in Patent Office: Days
• US Class Current: 514/456
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Nebivolol has been shown to be beneficial in the treatment of cardiovascular diseases such hypertension, congestive heart failure, arterial stiffness and endothelial dysfunction. The present invention features a pharmaceutical composition comprising nebivolol and at least one other active agent, wherein the at least one other active agent is a cardiovascular agent.

Claims

1-1. ) The composition of claim 1 wherein at least one of the other active agents is a cardiovascular agent.

2. ) The composition of claim 2 wherein the cardiovascular agent is selected from the group consisting of ACE inhibitors, ARB'"'"'s, adrenergic blockers, adrenergic agonists, agents for pheochromocytoma, antiarrhythmics, antiplatelet agents, anticoagulants, antihypertensives, antilipemic agents, antidiabetics, antiinflammatory agents, calcium channel blockers, CETP inhibitors, COX-2 inhibitors, direct thrombin inhibitors, diuretics, endothelin receptor antagonists, HMG Co-A reductase inhibitors, inotropic agents, rennin inhibitors, vasodialators, vasopressors, AGE crosslink breakers, AGE formation inhibitors, and mixtures thereof.

3. ) The composition of claim 2, wherein the cardiovascular agent is selected from the group consisting of an ACE inhibitor, an ARB, and mixtures thereof.

9. ) The composition of claim 2, wherein the cardiovascular agent is selected from the group consisting of AGE crosslink breakers, AGE formation inhibitors, and mixtures thereof.

4. ) The composition of claim 4, wherein the cardiovascular agent is an ACE inhibitor.

7. ) The composition of claim 4 wherein the cardiovascular agent is an ARB.

5. ) The composition of claim 5 wherein the ACE inhibitor is selected from the group consisting of alacepril, benazepril, captopril, ceronapril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, imidapril, lisinopril, perindopril, quinapril, ramipril, ramiprilat, spirapril, temocapril, trandolapril, and mixtures thereof.

6. ) The composition of claim 5 wherein the ACE inhibitor is selected from the group consisting of enalapril, ramipril and ramiprilat and mixtures thereof.

8. ) The composition of claim 8 wherein the ARB is selected from the group consisting of candesartan, eprosartan, irbesartan, losartan, valsartan, and mixtures thereof.

10. ) A composition comprising nebivolol and only one other active agent.

11. ) The composition of claim 11 wherein the other active agent is a cardiovascular agent.

12. ) The composition of claim 12 wherein the cardiovascular agent is selected from the group consisting of ACE inhibitors, ARB'"'"'s, adrenergic blockers, adrenergic agonists, agents for pheochromocytoma, antiarrhythmics, antiplatelet agents, anticoagulants, antihypertensives, antilipemic agents, antidiabetics, antiinflammatory agents, calcium channel blockers, CETP inhibitors, COX-2 inhibitors, direct thrombin inhibitors, diuretics, endothelin receptor antagonists, HMG Co-A reductase inhibitors, inotropic agents, rennin inhibitors, vasodialators, vasopressors, AGE crosslink breakers, AGE formation inhibitors, and mixtures thereof.

13. ) The composition of claim 12 wherein the cardiovascular agent is selected from the group consisting of ACE inhibitors, ARB'"'"'s.

14. ) The composition of claim 12 wherein the cardiovascular agent is an ACE inhibitor selected from the group consisting of alacepril, benazepril, captopril, ceronapril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, imidapril, lisinopril, perindopril, quinapril, ramipril, ramiprilat, spirapril, temocapril, and trandolapril.

15. ) The composition of claim 12, wherein the cardiovascular agent is an ARB selected from the group consisting of candesartan, eprosartan, irbesartan, losartan and valsartan.

16. ) The composition of claim 12 wherein the cardiovascular agent is selected from the group consisting of AGE crosslink breakers and AGE formation inhibitors.

17. ) A pharmaceutical composition comprising nebivolol and at least one other active agent, and a pharmaceutically-acceptable carrier.

18. ) The pharmaceutical composition of claim 18 wherein at least one of the other active agents is a cardiovascular agent.

35. ) The pharmaceutical composition as set forth in claims 18 and 19, wherein said composition comprises a pharmaceutical kit.

19. ) The pharmaceutical composition of claim 19 wherein the cardiovascular agent is selected from the group consisting of ACE inhibitors, ARB'"'"'s, adrenergic blockers, adrenergic agonists, agents for pheochromocytoma, antiarrhythmics, antiplatelet agents, anticoagulants, antihypertensives, antilipemic agents, antidiabetics, antiinflammatory agents, calcium channel blockers, CETP inhibitors, COX-2 inhibitors, direct thrombin inhibitors, diuretics, endothelin receptor antagonists, HMG Co-A reductase inhibitors, inotropic agents, rennin inhibitors, vasodialators, vasopressors, AGE crosslink breakers, AGE formation inhibitors, and mixtures thereof.

20. ) The pharmaceutical composition of claim 19, wherein the cardiovascular agent is selected from the group consisting of an ACE inhibitor, an ARB, and mixtures thereof.

26. ) The pharmaceutical composition of claim 19, wherein the cardiovascular agent is selected from the group consisting of AGE crosslink breakers, AGE formation inhibitors, and mixtures thereof.

21. ) The pharmaceutical composition of claim 21, wherein the cardiovascular agent is an ACE inhibitor.

24. ) The pharmaceutical composition of claim 21 wherein the cardiovascular agent is an ARB.

22. ) The pharmaceutical composition of claim 22 wherein the ACE inhibitor is selected from the group consisting of alacepril, benazepril, captopril, ceronapril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, imidapril, lisinopril, perindopril, quinapril, ramipril, ramiprilat, spirapril, temocapril, trandolapril, and mixtures thereof.

23. ) The pharmaceutical composition of claim 23 wherein the ACE inhibitor is selected from the group consisting of enalapril, ramipril and ramiprilat and mixtures thereof

25. ) The pharmaceutical composition of claim 25 wherein the ARB is selected from the group consisting of candesartan, eprosartan, irbesartan, losartan, valsartan, and mixtures thereof.

27. ) A method of treating and/or preventing a cardiovascular disorder comprising administering to a subject a therapeutically effective amount of nebivolol and at least one other active agent.

28. ) The method of claim 28 wherein the at least one other active agent is a cardiovascular agent.

30. ) The method of claim 28 wherein the cardiovascular disorder is selected from the group consisting of congestive heart failure, hypertension, pulmonary hypertension, myocardial and cerebral infarctions, atherosclerosis, atherogenesis, thrombosis, ischemic heart disease, post-angioplasty restenosis, coronary artery diseases, renal failure, stable, unstable and variant (Prinzmetal) angina, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, transient ischemic attacks, cerebrovascular accidents, restenosis, controlling blood pressure in hypertension, platelet adhesion, platelet aggregation, smooth muscle cell proliferation, pulmonary edema, vascular complications associated with the use of medical devices, wounds associated with the use of medical devices, pulmonary thromboembolism, cerebral thromboembolism, thrombophlebitis, thrombocytopenia and bleeding disorders.

31. ) The method of claim 30 wherein the wherein the cardiovascular agent is selected from the group consisting of ACE inhibitors, an ARB'"'"'s, and mixtures thereof.

34. ) The method of claim 30 wherein the cardiovascular agent is selected from the group consisting of AGE crosslink breakers, AGE formation inhibitors, and mixtures thereof.

29. ) The method of claim 29 wherein the cardiovascular agent is selected from the group consisting of ACE inhibitors, ARB'"'"'s, adrenergic blockers, adrenergic agonists, agents for pheochromocytoma, antiarrhythmics, antiplatelet agents, anticoagulants, antihypertensives, antilipemic agents, antidiabetics, antiinflammatory agents, calcium channel blockers, CETP inhibitors, COX-2 inhibitors, direct thrombin inhibitors, diuretics, endothelin receptor antagonists, HMG Co-A reductase inhibitors, inotropic agents, rennin inhibitors, vasodialators, vasopressors, AGE crosslink breakers, AGE formation inhibitors, and mixtures thereof.

32. ) The method of claim 32 wherein the cardiovascular agent is an ACE inhibitor.

33. ) The method of claim 32 wherein the cardiovascular agent is an ARB.