Pharmaceutical composition

Abstract

A pharmaceutical composition which comprises (i) an angiotensin II receptor antagonist having the following formula (I), a pharmacologically acceptable salt thereof, a pharmacologically acceptable ester thereof or a pharmacologically acceptable salt of such ester, and (ii) a diuretic which is at least one thiazide compound: The pharmaceutical composition has an excellent hypotensive effect and low toxicity, and therefore is useful as a medicament for treating hypertension or heart disease.

1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier in combination with a pharmaceutically effective amount of each of (i) an angiotensin II receptor antagonist selected from the group consisting of a compound having the following formula (I):  
       
         
           
           
               
               
           
         
       
       , a pharmacologically acceptable salt thereof, a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt of said ester thereof, and (ii) a diuretic which is at least one thiazide compound.  
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the angiotensin II receptor antagonist is the compound of the formula (I) or a pharmacologically acceptable ester thereof.  
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the angiotensin II receptor antagonist is a pharmacologically acceptable ester of the compound of the formula (I).  
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the angiotensin II receptor antagonist is the pivaloyloxymethyl ester, phthalidyl ester, or (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of the formula (I).  
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the angiotensin II receptor antagonist is the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of the formula (I).  
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein the diuretic is selected from the group consisting of hydrochlorothiazide, methylclothiazide, benzylhydrochlorothiazide, trichlormethiazide, cyclopenthiazide, polythiazide, ethiazide, cyclothiazide, bendroflumethiazide and hydroflumethiazide.  
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the diuretic is hydrochlorothiazide.  
     
     
         8 . The pharmaceutical composition according to  claim 1 , wherein the angiotensin II receptor antagonist is the pivaloyloxymethyl ester, phthalidyl ester, or (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of the formula (I) and the diuretic is selected from the group consisting of hydrochlorothiazide, methyldlothiazide, benzylhydrochlorothiazide, trichlormethiazide, cyclopenthiazide, polythiazide, ethiazide, cyclothiazide, bendroflumethiazide and hydroflumethiazide.  
     
     
         9 . The pharmaceutical composition according to  claim 1 , wherein the angiotensin II receptor antagonist is the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of the formula (I) and the diuretic is hydrochlorothiazide.  
     
     
         10 . The pharmaceutical composition according to  claim 1 , wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1.  
     
     
         11 . The pharmaceutical composition according to  claim 8 , wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1.  
     
     
         12 . The pharmaceutical composition according to  claim 9 , wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1.  
     
     
         13 . The pharmaceutical composition according to  claim 1 , wherein the composition has a hypotensive action.  
     
     
         14 . The pharmaceutical composition according to  claim 1 , wherein the angiotensin II receptor antagonist is in a first dosage form and the diuretic is in a second dosage form.  
     
     
         15 . The pharmaceutical composition according to  claim 1 , wherein the angiotensin II receptor antagonist and the diuretic are in a single unit dosage.  
     
     
         16 . A method for treating hypertension by administering to a warm-blooded animal a pharmaceutically effective amount of each of (i) an angiotensin II receptor antagonist selected from the group consisting of a compound having the following formula (I):  
       
         
           
           
               
               
           
         
       
       , a pharmacologically acceptable salt thereof, a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt of said ester thereof, and (ii) at least one diuretic selected from the group consisting of methylclothiazide, benzylhydrochlorothiazide, trichlormethiazide, cyclopenthiazide, polythiazide, ethiazide, cyclothiazide, bendroflumethiazide and hydroflumethiazide.  
     
     
         17 . The method according to  claim 16 , wherein the warm-blooded animal is a human.  
     
     
         18 . The method according to  claim 17 , wherein the angiotensin II receptor antagonist is the compound of the formula (I) or a pharmacologically acceptable ester thereof.  
     
     
         19 . The method according to  claim 17 , wherein the angiotensin II receptor antagonist is a pharmacologically acceptable ester of the compound of the formula (I).  
     
     
         20 . The method according to  claim 17 , wherein the angiotensin II receptor antagonist is the pivaloyloxymethyl ester, phthalidyl ester or (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of the formula (I).  
     
     
         21 . The method according to  claim 17 , wherein the angiotensin II receptor antagonist is the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of the formula (I).  
     
     
         22 . The method according to  claim 20 , wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1.  
     
     
         23 . The method according to  claim 21 , wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1.  
     
     
         24 . The method according to  claim 17 , wherein the compound of the formula (I) is administered at least once a day in an amount of 0.5 to 1,000 mg and the diuretic is administered at least once a day in an amount of 0.05 to 1,500 mg.  
     
     
         25 . The method according to  claim 17 , wherein the compound of the formula (I) is administered at least once a day in an amount of 1 to 100 mg and the diuretic is administered at least once a day in an amount of 5 to 300 mg.  
     
     
         26 . The method according to  claim 17 , wherein the angiotensin II receptor antagonist is in a first dosage form and the diuretic is in a second dosage form.  
     
     
         27 . The method according to  claim 17 , wherein the angiotensin II receptor antagonist and the diuretic are in a single dosage form.  
     
     
         28 . A method for preventing or treating a disease or condition selected from the group consisting of angina pectoris, cardiac failure, cardiac hypertrophy, arteriosclerosis, post-PTCA restenosis, a peripheral vascular disorder, diabetic nephropathy, glomerular nephritis and nephrosclerosis, comprising administering to a warm-blooded animal a pharmaceutically effective amount of each of (i) an angiotensin II receptor antagonist selected from the group consisting of a compound having the following formula (I):  
       
         
           
           
               
               
           
         
       
       , a pharmacologically acceptable salt thereof, a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt of said ester thereof, and (ii) at least one diuretic.  
     
     
         29 . The method according to  claim 28 , wherein the method is for treating a human.  
     
     
         30 . The method according to  claim 29 , wherein the angiotensin II receptor antagonist is the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of the formula (I) and the diuretic is hydrochlorothiazide.  
     
     
         31 . The method according to  claim 30 , wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1.  
     
     
         32 . The method according to  claim 28 , wherein the angiotensin II receptor antagonist is in a first dosage form and the diuretic is in a second dosage form.  
     
     
         33 . The method according to  claim 29 , wherein the angiotensin H receptor antagonist and the diuretic are in a single unit dosage.