METHOD OF REVERSING LEFT VENTRICULAR REMODELING
The present invention relates to method of reversing left ventricle remodeling by combined administration of therapeutically effective amounts ranolazine and at least one co-remodeling agent, which may be an ACE inhibitor, an ARB, or a beta-blocker. The method finds utility in the treatment of heart failure. This invention also relates to pharmaceutical formulations that are suitable for such combined administration.
1 . A method for reversing unfavorable left ventricle remodeling comprising administration of a therapeutically effective amount of ranolazine and a therapeutically effective amount of at least one co-remodeling agent to a mammal in need thereof.
2 . The method of claim 1 , wherein the co-remodeling agent comprises an ACE inhibitor, an ARB, or a beta-blocker.
3 . The method of claim 2 , wherein the co-remodeling agent comprises an ACE inhibitor.
4 . The method of claim 3 , wherein the ACE inhibitor is selected from the group consisting of benazepril, captopril, cilazapril, enalapril, fosinopril, imidapril, lisinopril, perindopril, quinapril, ramipril, temocapril, and trandolapril.
5 . The method of claim 2 , wherein the co-remodeling agent comprises an ARB.
6 . The method of claim 5 , wherein the ARB is selected from the group consisting of candesartan, cilexetil, eprosartan, irbesartan, losartan, olmesartan, medoxomil, telmisartan, valsartan, zolasartin, and tasosartan.
7 . The method of claim 2 , wherein the co-remodeling agent comprises a beta-blocker.
8 . The method of claim 7 , wherein the beta-blocker is selected from the group consisting of, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, labetalol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol, esmolol, sotalol, carvedilol, medroxalol, bucindolol, levobunolol, metipranolol, celiprolol, and propafenone.
9 . The method of claim 2 , wherein the left ventricle remodeling is the result of congestive heart failure (CHF) and/or chronic heart failure.
10 . The method of claims 1 , wherein the ranolazine and the co-remodeling agent are administered as separate dosage forms.
11 . The method of claim 1 , wherein ranolazine and the co-remodeling agent are administered as a single dosage form.
12 . A pharmaceutical formulation comprising a therapeutically effective amount of ranolazine, a therapeutically effective amount at least one co-remodeling agent, and at least one pharmaceutically acceptable carrier.
13 . The formulation of claim 12 , wherein the co-remodeling agent comprises an ACE inhibitor, an ARB, or a beta-blocker.
14 . The formulation of claim 13 , wherein the co-remodeling agent comprises an ACE inhibitor.
15 . The formulation of claim 14 , wherein the ACE inhibitor is selected from the group consisting of benazepril, captopril, cilazapril, enalapril, fosinopril, imidapril, lisinopril, perindopril, quinapril, ramipril, temocapril, and trandolapril.
16 . The formulation of claim 13 , wherein the co-remodeling agent comprises an ARB.
17 . The formulation of claim 16 , wherein the ARB is selected from the group consisting of candesartan, cilexetil, eprosartan, irbesartan, losartan, olmesartan, medoxomil, telmisartan, valsartan, zolasartin, and tasosartan.
18 . The formulation of claim 13 , wherein the co-remodeling agent comprises a beta-blocker.
19 . The formulation of claim 18 wherein the beta-blocker is selected from the group consisting of, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, labetalol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol, esmolol, sotalol, carvedilol, medroxalol, bucindolol, levobunolol, metipranolol, celiprolol, and propafenone.
20 . A method for treating heart failure comprising administration of a therapeutically effective amount of ranolazine and a therapeutically effective amount of at least one co-remodeling agent to a mammal in need thereof.
21 . The method of claim 20 , wherein the co-remodeling agent comprises an ACE inhibitor, an ARB, or a beta-blocker.
22 . The method of claim 21 , wherein the co-remodeling agent comprises an ACE inhibitor.
23 . The method of claim 22 , wherein the ACE inhibitor is selected from the group consisting of benazepril, captopril, cilazapril, enalapril, fosinopril, imidapril, lisinopril, perindopril, quinapril, ramipril, temocapril, and trandolapril.
24 . The method of claim 21 , wherein the co-remodeling agent comprises an ARB.
25 . The method of claim 24 , wherein the ARB is selected from the group consisting of candesartan, cilexetil, eprosartan, irbesartan, losartan, olmesartan, medoxomil, telmisartan, valsartan, zolasartin, and tasosartan.
26 . The method of claim 21 , wherein the co-remodeling agent comprises a beta-blocker.
27 . The method of claim 26 , wherein the beta-blocker is selected from the group consisting of, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, labetalol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol, esmolol, sotalol, carvedilol, medroxalol, bucindolol, levobunolol, metipranolol, celiprolol, and propafenone.
28 . The method of claim 21 , wherein the heart failure is congestive heart failure (CHF) or chronic heart failure.
29 . The method of claims 20 , wherein the ranolazine and the co-remodeling agent are administered as separate dosage forms.
30 . The method of claim 20 , wherein ranolazine and the co-remodeling agent are administered as a single dosage form.