Compositions and Methods for the Treatment of Heart Failure

Abstract

The invention provides a therapeutic composition comprising an aqueous buffer, and a therapeutic agent that proves the functioning of a diseased heart by decreasing left ventricular end-diastolic pressure and simultaneously increasing left ventricular ejection without affecting the blood pressure or heart rate.

1 . A therapeutic composition comprising:
 an aqueous buffer, and   a therapeutic agent that improves the functioning of a diseased heart by decreasing left ventricular end-diastolic pressure or increasing left ventricular ejection without significantly affecting the blood pressure or heart rate.   
     
     
         2 . (canceled) 
     
     
         3 . The therapeutic composition of  claim 1 , wherein the therapeutic composition improves the functioning of the diseased heart continuously for at least 24 hours following each administration of the therapeutic composition. 
     
     
         4 - 6 . (canceled) 
     
     
         7 . The therapeutic composition of  claim 1 , wherein the therapeutic agent improves the functioning of a diseased heart independently of its concentration in the blood for at least 24 hours following each single administration of the therapeutic composition. 
     
     
         8 . (canceled) 
     
     
         9 . The therapeutic composition of  claim 1 , wherein the therapeutic agent is a polyoxyalkylene block copolymer. 
     
     
         10 . The therapeutic composition of  claim 9 , wherein the therapeutic agent has a molecular weight in the range of 3,000 to 18,000. 
     
     
         11 . The therapeutic composition of  claim 10 , wherein the therapeutic agent is a poloxamer or poloxamine. 
     
     
         12 . The therapeutic composition of  claim 11 , wherein the therapeutic agent is one or more compounds selected from the group consisting of Poloxamer 188, Poloxamer 407, Poloxamer 338, and Poloxamine 1107. 
     
     
         13 . The therapeutic composition of  claim 12 , wherein the therapeutic agent is Poloxamer 188. 
     
     
         14 - 16 . (canceled) 
     
     
         17 . The therapeutic composition of  claim 1 , wherein the therapeutic composition is injectable or infusible. 
     
     
         18 . The therapeutic composition of  claim 1 , wherein the disease of the heart is heart failure. 
     
     
         19 . The therapeutic composition of  claim 18 , wherein the disease of the heart is chronic heart failure or acute heart failure. 
     
     
         20 . (canceled) 
     
     
         21 . The therapeutic composition of  claim 18 , wherein the disease of the heart is ischemic heart failure. 
     
     
         22 . The therapeutic composition of  claim 1 , further comprising an agent selected from the group consisting of angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs); beta-blockers, diuretics, digoxin, and anti-arrhythmic drugs. 
     
     
         23 . The therapeutic composition of  claim 22 , wherein the ACE inhibitors consist of captopril, benazepril, enalapril, lisinopril, fosinopril, ramipril, perindopril, quinapril, moexipril, and trandolapril; ARBs consist of losartan, candesartan, irbesartan, and valsartan; beta-blockers consist of alprenolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol, acebutolol, atenolol, betaxolol, bisoprolol, esmolol, metoprolol, nebivolol, carvedilol, celiprolol, labetalol, and butaxamine; diuretics consist of calcium chloride, ammonium chloride, amphotericin B, lithium citrate, Goldenrod, Juniper, dopamine, acetazolamide, dorzolamide, bumetanide, ethacrynic acid, furosemide, torsemide, glucose, mannitol, amiloride, spironolactone, triamterene, bendroflumethiazide, hydrochlorothiazide, caffeine, and theophylline; anti-arrhythmic drugs consist of disopyramide, procainamide, quinidine, lidocaine, phenyloin, flecamide, propafenone, propranolol, timolol, metoprolol, sotalol, atenolol, amiodarone, sotalol, bretylium, verapamil, and diltiazem. 
     
     
         24 . A method of treating, ameliorating, or preventing heart failure in a subject, comprising administering to the subject in need thereof a therapeutic composition comprising
 an aqueous buffer, and   a therapeutic agent that improves the functioning of a diseased heart by decreasing left ventricular end-diastolic pressure or increasing left ventricular ejection without substantially affecting the blood pressure or heart rate.   
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 24 , wherein the therapeutic composition improves the functioning of the diseased heart continuously for at least 24 hours following each administration of the therapeutic composition. 
     
     
         27 - 29 . (canceled) 
     
     
         30 . The method of  claim 24 , wherein the therapeutic agent improves the functioning of a diseased heart independently of its concentration in the blood for at least 24 hours following each single administration of the therapeutic composition. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 24 , wherein the therapeutic agent is a polyoxyalkylene block copolymer. 
     
     
         33 . The method of  claim 32 , wherein the therapeutic agent has a molecular weight in the range of 3,000 to 18,000. 
     
     
         34 . The method of  claim 33 , wherein the therapeutic agent is a poloxamer or poloxamine. 
     
     
         35 . The method of  claim 34 , wherein the therapeutic agent is one or more compounds selected from the group consisting of Poloxamer 188, Poloxamer 407, Poloxamer 338, and Poloxamine 1107. 
     
     
         36 . The method of  claim 35 , wherein the therapeutic agent is Poloxamer 188. 
     
     
         37 - 39 . (canceled) 
     
     
         40 . The method of  claim 24 , wherein the heart failure is acute heart failure. 
     
     
         41 . The method of  claim 24 , wherein the heart failure is chronic heart failure. 
     
     
         42 . The method of  claim 41 , wherein the heart failure is ischemic heart failure. 
     
     
         43 . The method of  claim 24 , wherein the therapeutic composition is administered by injection or infusion. 
     
     
         44 . The method of  claim 24 , wherein the therapeutic agent in the composition is administered to the patient in the amount of 0.15 mg/kg to about 480 mg/kg. 
     
     
         45 . The method of  claim 44 , wherein the therapeutic agent in the composition is administered to the patient in the amount of about 460 mg/kg. 
     
     
         46 . The method of  claim 44 , wherein the therapeutic agent in the composition is administered to the patient in the amount of about 250 mg/kg. 
     
     
         47 . The method of  claim 44 , wherein the therapeutic agent in the composition is administered to the patient in the amount of about 15.3 mg/kg. 
     
     
         48 . The method of  claim 44 , wherein the therapeutic agent in the composition is administered to the patient in the amount of about 4.6 mg/kg. 
     
     
         49 . The method of  claim 44 , wherein the therapeutic agent in the composition is administered to the patient in the amount of about 1.5 mg/kg. 
     
     
         50 . The method of  claim 44 , wherein the therapeutic agent in the composition is administered to the patient in the amount of about 0.46 mg/kg. 
     
     
         51 . The method of  claim 24 , further comprising administering to the subject an agent selected from a group consisting of angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, diuretics, digoxin, and anti-arrhythmic drugs. 
     
     
         52 . The method of  claim 51 , wherein the ACE inhibitors consist of captopril, benazepril, enalapril, lisinopril, fosinopril, ramipril, perindopril, quinapril, moexipril, and trandolapril; ARBs consist of losartan, candesartan, irbesartan, and valsartan; beta-blockers consist of alprenolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol, acebutolol, atenolol, betaxolol, bisoprolol, esmolol, metoprolol, nebivolol, carvedilol, celiprolol, labetalol, and butaxamine; diuretics consist of calcium chloride, ammonium chloride, amphotericin B, lithium citrate, Goldenrod, Juniper, dopamine, acetazolamide, dorzolamide, bumetanide, ethacrynic acid, furosemide, torsemide, glucose, mannitol, amiloride, spironolactone, triamterene, bendroflumethiazide, hydrochlorothiazide, caffeine, and theophylline; anti-arrhythmic drugs consist of disopyramide, procainamide, quinidine, lidocaine, phenyloin, flecamide, propafenone, propranolol, timolol, metoprolol, sotalol, atenolol, amiodarone, sotalol, bretylium, verapamil, and diltiazem.