Therapeuctic combination

Abstract

This invention relates to pharmaceutical combinations of amlodipine or a pharmaceutically acceptable acid addition salt thereof and atorvastatin or a pharmaceutically acceptable salt thereof, kits containing such combinations and methods of using such combinations to treat subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and to treat subjects presenting with symptoms of cardiac risk, including humans. This invention also relates to additive and synergistic combinations of amlodipine and atorvastatin whereby those synergistic combinations are useful in treating subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and those subjects presenting with symptoms of cardiac risk, inducing humans.

1 . A pharmaceutical composition comprising: 
 a. an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof;    b. an amount of atorvastatin or a pharmaceutically acceptable salt thereof; and    c. a pharmaceutically, acceptable carrier or diluent.    
     
     
         2 . A pharmaceutical composition of  claim 1  comprising amlodipin besylate.  
     
     
         3 . A pharmaceutical composition of  claim 2  comprising the hemicalcium salt of atorvastatin.  
     
     
         4 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving a antihypertensive effect and a hypolipidemic effect in a mammal suffering from hypertension and hyperlipidemia, which effects are greater than the sum of the antihypertensive and hypolipidemic effects achieved by administering said first and second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         5 . A first pharmaceutical composition of  claim 4  wherein said second pharmaceutical composition comprises amlodipine besylate.  
     
     
         6 . A first pharmaceutical composition of  claim 5  comprising the hemicalcium salt of atorvastatin.  
     
     
         7 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving a antihypertensive effect and a hypolipidemic effect in a mammal suffering from hypertension and hyperlipidemia, which effects are greater than the sum of the antihypertensive and hypolipidemic effects achieved by administering said first and second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         8 . A first pharmaceutical composition of  claim 7  comprising amlodipine besylate.  
     
     
         9 . A first pharmaceutical composition of  claim 8  wherein said second pharmaceutical composition comprises the hemicalcium salt of atorvastatin.  
     
     
         10 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving a antihypertensive effect and a hypolipidemic effect in a mammal suffering from hypertension and hyperlipidemia, which effects are greater than the antihypertensive and hypolipidemic effects achieved by administering said first or second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         11 . A first pharmaceutical composition of  claim 10  comprising amlodipine besylate.  
     
     
         12 . A first pharmaceutical composition of  claim 11  wherein said second pharmaceutical composition comprises the hemicalcium salt of atorvastatin.  
     
     
         13 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving a antihypertensive effect and a hypolipidemic effect in a mammal suffering from hypertension and hyperlipidemia, which effects are greater than the antihypertensive and hypolipidemic effects achieved by administering said first or second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         14 . A first pharmaceutical composition of  claim 13  wherein said second pharmaceutical composition comprises amlodipine besylate.  
     
     
         15 . A first pharmaceutical composition of  claim 14  comprising the hemicalium salt of atorvastatin.  
     
     
         16 . A first pharmaceutical composition for us with a second pharmaceutical composition for achieving an antiangina effect in a mammal suffering from anginal pectoris, which effect is greater than the sum of the antiangina effects achieved by administering said first and second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         17 . A first pharmaceutical composition of  claim 16  comprising amlodipine besylate.  
     
     
         18 . A first pharmaceutical composition of  claim 17  wherein said second pharmaceutical composition comprises the hemicalcium salt of atorvastatin.  
     
     
         19 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving an antianginal effect in a mammal suffering from angina pectoris, which effect is greater than the sum of the antiangina effects achieved by administering said first and second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         20 . A first pharmaceutical composition of  claim 19  wherein said second pharmaceutical composition comprises amlodipine besylate.  
     
     
         21 . A first pharmaceutical composition of  claim 20  comprising the hemicalcium salt of atorvastatin.  
     
     
         22 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving an antianginal effect in a mammal suffering from angina pectoris, which effect is greater than the antianginal effects achieved by administering said first or second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent. acceptable carrier or diluent.  
     
     
         23 . A first pharmaceutical composition of  claim 22  comprising amlodipine besylate.  
     
     
         24 . A first pharmaceutical composition of  claim 23  wherein said second pharmaceutical composition comprises the hemicalcium salt of atorvastatin.  
     
     
         25 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving an antianginal effect in a mammal suffering from angina pectoris, which effect is greater than the antianginal effects achieved by administering said first or second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         26 . A first pharmaceutical composition of  claim 25  wherein said second pharmaceutical composition comprises amlodipine besylate.  
     
     
         27 . A first pharmaceutical composition of  claim 26  comprising the hemicalcium salt of atorvastatin.  
     
     
         28 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving an antiatherosclerotic effect in a mammal, which effect is greater than the sum of the antiatherosclerotic effects achieved by administering said first and second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         29 . A first pharmaceutical composition of  claim 28  wherein said second pharmaceutical composition comprises amlodipine besylate.  
     
     
         30 . A first pharmaceutical composition of  claim 29  comprising the hemicalcium salt of atorvastatin.  
     
     
         31 . A composition of  claim 30  wherein said antiatherosclerotic effect is manifested by a slowing of the progression of atherosclerotic plaques.  
     
     
         32 . A composition of  claim 31  wherein said progression of atherosclerotic plaques is slowed in coronary arteries.  
     
     
         33 . A composition of  claim 31  wherein said progression of atherosclerotic plaques is slowed in carotid arteries.  
     
     
         34 . A composition of  claim 31  wherein said progression of atherosclerotic plaques is slowed in the peripheral arterial system.  
     
     
         35 . A composition of  claim 30  wherein said antiatherosclerotic effect is manifested by a regression of atherosclerotic plaques.  
     
     
         36 . A composition of  claim 35  wherein said regression of atherosclerotic plaques occurs in coronary arteries.  
     
     
         37 . A composition of  claim 35  wherein said regression of atherosclerotic plaques occurs in carotid arteries.  
     
     
         38 . A composition of  claim 35  wherein said regression of atherosclerotic plaques occurs in the peripheral arterial system.  
     
     
         39 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving an antiatherosclerotic effect in a mammal, which effect is greater than the sum of the antiatherosclerotic effects achieved by administering said first and second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carder or diluent, said first pharmaceutical composition comprising an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         40 . A first pharmaceutical composition of  claim 39  comprising amlodipine besylate.  
     
     
         41 . A first pharmaceutical composition of  claim 40  wherein said second pharmaceutical composition comprises the hemicalcium salt of atorvastatin.  
     
     
         42 . A composition of  claim 41  wherein said antiatherosclerotic effect is manifested by a slowing of the progression of atherosclerotic plaques.  
     
     
         43 . A composition of  claim 42  wherein said progression of atherosclerotic plaques is slowed in coronary arteries.  
     
     
         44 . A composition of  claim 42  wherein said progression of atherosclerotic plaques is slowed in carotid arteries.  
     
     
         45 . A composition of  claim 42  wherein said progression of atherosclerotic plaques is slowed in the peripheral arterial system.  
     
     
         46 . A composition of  claim 41  wherein said antiatherosclerotic effect is manifested by a regression of atherosclerotic plaques.  
     
     
         47 . A composition of  claim 46  wherein said regression of atherosclerotic plaques occurs in coronary arteries.  
     
     
         48 . A composition of  claim 46  wherein said regression of atherosclerotic plaques occurs in carotid arteries.  
     
     
         49 . A composition of  claim 46  wherein said regression of atherosclerotic plaques occurs in the peripheral arterial system.  
     
     
         50 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving an antiatherosclerotic effect in a mammal, which effect is greater than the antiatherosclerotic effects achieved by administering said first or second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         51 . A first pharmaceutical composition of  claim 50  comprising amlodipin besylate.  
     
     
         52 . A first pharmaceutical composition of  claim 51  wherein said second pharmaceutical composition comprises the hemicalcium salt of atorvastatin.  
     
     
         53 . A composition of  claim 52  wherein said antiatherosclerotic effect is manifested by a slowing of the progression of atherosclerotic plaques.  
     
     
         54 . A composition of  claim 53  wherein said progression of atherosclerotic plaques is slowed in coronary arteries.  
     
     
         55 . A composition of  claim 53  wherein said progression of atherosclerotic plaques is slowed in carotid arteries.  
     
     
         56 . A composition of  claim 53  wherein said progression of atherosclerotic plaques is slowed in the peripheral arterial system.  
     
     
         57 . A composition of  claim 52  wherein said antiatherosclerotic effect is manifested by a regression of atherosclerotic plaques.  
     
     
         58 . A composition of  claim 57  wherein said regression of atherosclerotic plaques occurs in coronary arteries.  
     
     
         59 . A composition of  claim 57  wherein said regression of atherosclerotic plaques occurs in carotid arteries.  
     
     
         60 . A composition of  claim 57  wherein said regression of atherosclerotic plaques occurs in the peripheral arterial system.  
     
     
         61 . A first pharmaceutical composition for use with a second pharmaceutical composition for achieving an antiatherosclerotic effect in a mammal, which effect is greater than the antiatherosclerotic effects achieved by administering said first or second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         62 . A first pharmaceutical composition of  claim 61  wherein said second pharmaceutical composition comprises amlodipine besylate.  
     
     
         63 . A first pharmaceutical composition of  claim 62  comprising the hemicalcium salt of atorvastatin.  
     
     
         64 . A composition of  claim 63  wherein said antiatherosclerotic effect is manifested by a slowing of the progression of atherosclerotic plaques.  
     
     
         65 . A composition of  claim 64  wherein said progression of atherosclerotic plaques is slowed in coronary arteries.  
     
     
         66 . A composition of  claim 64  wherein said progression of atherosclerotic plaques is slowed in carotid arteries.  
     
     
         67 . A composition of  claim 64  wherein said progression of atherosclerotic plaques is slowed in the peripheral arterial system.  
     
     
         68 . A composition of  claim 63  wherein said antiatherosclerotic effect is manifested by a regression of atherosclerotic plaques.  
     
     
         69 . A composition of  claim 68  wherein said regression of atherosclerotic plaques occurs in coronary arteries.  
     
     
         70 . A composition of  claim 68  wherein said regression of atherosclerotic plaques occurs in carotid arteries.  
     
     
         71 . A composition of  claim 68  wherein said regression of atherosclerotic plaques occurs in the peripheral arterial system.  
     
     
         72 . A first pharmaceutical composition for use with a second pharmaceutical composition for managing cardiac risk in a mammal at risk of suffering an adverse cardiac event, which effect is greater than the sum of the cardiac risk management effects achieved by administering said first and second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         73 . A first pharmaceutical composition of  claim 72  comprising amlodipine besylate.  
     
     
         74 . A first pharmaceutical composition of  claim 73 , wherein said second pharmaceutical composition comprises the hemicalcium salt of atorvastatin.  
     
     
         75 . A first pharmaceutical composition for use with a second pharmaceutical composition for managing cardiac risk in a mammal at risk of suffering an adverse cardiac event, which effect is greater than the sum of the cardiac risk management effects achieved by administering said first and second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         76 . A first pharmaceutical composition of  claim 75  wherein said second pharmaceutical composition comprises amlodipine besylate.  
     
     
         77 . A first pharmaceutical composition of  claim 76  comprising the hemicalcium salt of atorvastatin.  
     
     
         78 . A first pharmaceutical composition for use with a second pharmaceutical composition for managing cardiac risk in a mammal at risk of suffering an adverse cardiac event, which effect is greater than the cardiac risk management effects achieved by administering said first or second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         79 . A first pharmaceutical composition of  claim 78  comprising amlodipine besylate.  
     
     
         80 . A first pharmaceutical composition of  claim 79  wherein said second pharmaceutical composition comprises the hemicalcium salt of atorvastatin.  
     
     
         81 . A first pharmaceutical composition for use with a second pharmaceutical composition for managing cardiac risk in a mammal at risk of suffering an adverse cardiac event, which effect is greater than the cardiac risk management effects achieved by administering said first or second pharmaceutical compositions separately and which second pharmaceutical composition comprises an amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent, said first pharmaceutical composition comprising an amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.  
     
     
         82 . A first pharmaceutical composition of  claim 81  wherein said second pharmaceutical composition comprises amlodipine besylate.  
     
     
         83 . A first pharmaceutical composition of  claim 82  comprising th hemicalcium salt of atorvastatin.  
     
     
         84 . A kit for achieving a therapeutic effect in a mammal comprising: 
 a. a therapeutically effective amount of amlodipine or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent in a first unit dosage form;    b. a therapeutically effective amount of atorvastatin or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent in a second unit dosage form; and    c. container means for containing said first and second dosage forms.    
     
     
         85 . A kit of  claim 84  comprising amlodipine besylate.  
     
     
         86 . A kit of  claim 85  comprising the hemicalcium salt of atorvastatin.  
     
     
         87 . A kit of  claim 86  wherein said therapeutic effect is treatment of hypertension and hyperlipidemia.  
     
     
         88 . A kit of  claim 86  wherein said therapeutic effect is treatment of angina pectoris.  
     
     
         89 . A kit of  claim 86  wherein said therapeutic effect is management of cardiac risk.  
     
     
         90 . A kit of  claim 86  wherein said therapeutic effect is treatment of atherosclerosis.  
     
     
         91 . A kit of  claim 90  wherein said treatment of atherosclerosis slows the progression of atherosclerotic plaques.  
     
     
         92 . A kit of  claim 91  wherein said progression of atherosclerotic plaques is slowed in coronary arteries.  
     
     
         93 . A kit of  claim 91  wherein said progression of atherosclerotic plaques is slowed in carotid arteries.  
     
     
         94 . A kit of  claim 91  wherein said progression of atherosclerotic plaques is slowed in the peripheral arterial system.  
     
     
         95 . A kit of  claim 90  wherein said treatment of atherosclerosis causes the regression of atherosclerotic plaques.  
     
     
         96 . A kit of  claim 95  wherein said regression of atherosclerotic plaques occurs in coronary arteries.  
     
     
         97 . A kit of  claim 95  wherein said regression of atherosclerotic plaques occurs in carotid arteries.  
     
     
         98 . A kit of  claim 95  wherein said regression of atherosclerotic plaques occurs in the peripheral arterial system.  
     
     
         99 . A method for treating a mammal in need of therapeutic treatment comprising administering to said mammal 
 (a) an amount of a first compound, said first compound being amlodipine or a pharmaceutically acceptable acid addition salt thereof; and    (b) an amount of a second compound, said second compound being atorvastatin or a pharmaceutically acceptable salt thereof; wherein said first compound and said second compound are each optionally and independently administered together with a pharmaceutically acceptable carrier or diluent.    
     
     
         100 . A method of  claim 99  comprising amlodipine besylate.  
     
     
         101 . A method of  claim 100  comprising the hemicalcium salt of atorvastatin.  
     
     
         102 . A method of  claim 99  wherein said first compound and said second compound are administered simultaneously.  
     
     
         103 . A method of  claim 99  wherein said first compound and said second compound are administered sequentially in either order.  
     
     
         104 . A method of  claim 101  wherein said first compound and said second compound are administered simultaneously.  
     
     
         105 . A method of  claim 101  wherein said first compound and said second compound are administered sequentially in either order.  
     
     
         106 . A method of  claim 99  wherein said therapeutic treatment comprises antihypertensive treatment and anthyperlipidemic treatment.  
     
     
         107 . A method of  claim 104  wherein said therapeutic treatment comprises antihypertensive treatment and anthyperlipidemic treatment.  
     
     
         108 . A method of  claim 105  wherein said therapeutic treatment comprises antihypertensive treatment and anthyperlipidemic treatment.  
     
     
         109 . A method of  claim 99  wherein said therapeutic treatment comprises antianginal treatment.  
     
     
         110 . A method of  claim 104  wherein said therapeutic treatment comprises antianginal treatment.  
     
     
         111 . A method of  claim 105  wherein said therapeutic treatment comprises antianginal treatment.  
     
     
         112 . A method of  claim 99  wherein said therapeutic treatment comprises cardiac risk management.  
     
     
         113 . A method of  claim 104  wherein said therapeutic treatment comprises cardiac risk management.  
     
     
         114 . A method of  claim 105  wherein said therapeutic treatment comprises cardiac risk management.  
     
     
         115 . A method of  claim 99  wherein said therapeutic treatment comprises antiatherosclerotic treatment.  
     
     
         116 . A method of  claim 104  wherein said therapeutic treatment comprises antiatherosclerotic treatment.  
     
     
         117 . A method of  claim 105  wherein said therapeutic treatment comprises antiatherosclerotic treatment.