Pharmaceutical composition containing antihypertensive agents

Abstract

The present invention relates to a combination of organic compounds, a pharmaceutical composition and a kit of parts comprising said combination of organic compounds and to a method of treatment or prevention of certain conditions or diseases.

1 . A pharmaceutical composition comprising
 (i) an angiotensin receptor blocker (ARB) or a pharmaceutically acceptable salt thereof,   (ii) a calcium channel blocker (CCB) or a pharmaceutically acceptable salt thereof, and   (iii) a diuretic or a pharmaceutically acceptable salt thereof.   
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein (i) the angiotensin receptor blocker (ARB) is selected from the group consisting of candesartan, eprosartan, irbesartan, losartan, olmesartan, saprisartan, tasosartan, telmisartan, valsartan, E4177, SC-52458, and ZD8731; (ii) the calcium channel blocker (CCB) is selected from the group consisting of amlodipine, felodipine, isradipine, lacidipine, nicardipine, nifedipine, niguldipine, niludipine, nimodipine, nisoldipine, nitrendipine, nivaldipine, ryosidine, anipamil, diltiazem, fendiline, flunarizine, gallopamil, mibefradil, prenylamine, tiapamil, and verapamil; and (iii) the diuretic is selected from the group consisting of bumetanide, ethacrynic acid, furosemide, torsemide, amiloride, spironolactone, triamterene, chlorothalidone, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methylchlorothiazide, metolazone, and dichlorphenamide. 
     
     
         3 . A pharmaceutical composition according to  claim 2 , wherein (i) the angiotensin receptor blocker (ARB) is valsartan; (ii) the calcium channel blocker (CCB) is amlodipine; and (iii) the diuretic is hydrochlorothiazide. 
     
     
         4 . A pharmaceutical composition according to  claim 3 , wherein valsartan is contained in an amount from about 20 to about 640 mg, amlodipine is contained in an amount from about 1 mg to about 60 mg, and hydrochlorothiazide is contained in an amount from about 5 mg to about 200 mg. 
     
     
         5 . A pharmaceutical composition according to  claim 4 , wherein valsartan is contained in an amount from about 40 to about 320 mg, amlodipine is contained in an amount from about 2.5 mg to about 10 mg, and hydrochlorothiazide is contained in an amount from about 5 mg to about 25 mg. 
     
     
         6 . A kit of parts comprising
 (i) a pharmaceutical composition of an angiotensin receptor blocker (ARB),   (ii) a pharmaceutical composition of a calcium channel blocker (CCB), and   (iii) a pharmaceutical composition of a diuretic   in the form of two or three separate units of the components (i) to (iii).   
     
     
         7 . A kit of parts according to  claim 6 , wherein (i) the angiotensin recepror blocker (ARB) is selected from the group consisting of candesartan, eprosartan, irbesartan, losartan, olmesartan, saprisartan, tasosartan, telmisartan, valsartan, E-4177, SC-52458, and ZD8731; (ii) the calcium channel blocker (CCB) is selected from the group consisting of amlodipine, felodipine, isradipine, lacidipine, nicardipine, nifedipine, niguldipine, niludipine, nimodipine, nisoldipine, nitrendipine, nivaldipine, ryosidine, anipamil, diltiazem, fendiline, flunarizine, gallopamil, mibefradil, prenylamine, tiapamil, and verapamil; and (iii) the diuretic is selected from the group consisting of bumetanide, ethacrynic acid, furosemide, torsemide, amiloride, spironolactone, triamterene, chlorothalidone, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methylchlorothiazide, metolazone, and dichlorphenamide. 
     
     
         8 . A kit of parts according to  claim 7 , wherein (i) the angiotensin receptor blocker (ARB) is valsartan; (ii) the calcium channel blocker (CCB) is amlodipine; and (iii) the diuretic is hydrochlorothiazide. 
     
     
         9 . A kit of parts according to  claim 8 , wherein valsartan is contained in an amount from about 20 to about 640 mg, amlodipine ins contained in an amount from about 1 mg to about 60 mg, and hydrochlorothiazide is contained in an amount from about 5 mg to about 200 mg. 
     
     
         10 . A kit of parts according to  claim 9 , wherein valsartan is contained in an amount from about 40 to about 320 mg, amlodipine ins contained in an amount from about 2.5 mg to about 10 mg, and hydrochlorothiazide is contained in an amount from about 5 mg to about 25 mg. 
     
     
         11 . A method of treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke, comprising administering a therapeutically effective amount of combination of (i) an ARB selected from the group consisting of candesartan, eprosartan, irbesartan, losartan, olmesartan, saprisartan, tasosartan, telmisartan, valsartan, E-4177, SC-52458, and ZD8731, or a pharmaceutically acceptable salt thereof; and (ii) a CCB selected from the group consisting of amlodipine, felodipine, isradipine, lacidipine, nicardipine, nifedipine, niguldipine, niludipine, nimodipine, nisoldipine, nitrendipine, nivaldipine, and ryosidine, which all belong to the group of dihydropyridines (DHPs) and the non-DHP CCBs anipamil, diltiazem, fendiline, flunarizine, gallopamil, mibefradil, prenylamine, tiapamil, and verapamil, or a pharmaceutically acceptable salt thereof; and (iii) a diuretic selected from the group consisting of bumetanide, ethacrynic acid, furosemide, torsemide, amiloride, spironolactone, triamterene, chiorothalidone, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyichlorothiazide, metolazone, and dichlorphenamide, or, where appropriate, a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier to a mammal in need of such treatment. 
     
     
         12 . A commercial package comprising
 (i) a pharmaceutical composition of an angiotensin receptor blocker (ARB),   (ii) a pharmaceutical composition of a calcium channel blocker (CCB), and   (iii) a pharmaceutical composition of a diuretic,   in the form of two or three separate units of the components (i) to (iii), together with instructions for simultaneous, separate or sequential use thereof for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke   
     
     
         13 . A commercial package according to  claim 12 , wherein (i) the angiotensin receptor blocker (ARB) is valsartan; (ii) the calcium channel blocker (CCB) is amlodipine; and (iii) the diuretic is hydrochlorothiazide. 
     
     
         14 . A commercial package according to  claim 13 , wherein the angiotensin receptor blocker (ARB) (i) and the diuretic (iii) are present in the form of Co-DIOVAN® or wherein the angiotensin receptor blocker (ARB) (i), the CCB (ii) and the diuretic (iii) are present in the form of Co-DIOVAN® and Norvasc®. 
     
     
         15 . A method for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke comprising administering a composition according to  claim 1 . 
     
     
         16 . A method for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke comprising administering a composition according to  claim 2 . 
     
     
         17 . A method for the treatment or prevention of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic) heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke, comprising administering the kit of parts of  claim 6 .