Methods for prevention and treatment of arteriosclerosis, hypertension and restenosis

A method for the prevention and/or treatment of hypertension comprising administering to a mammal in need thereof a pharmaceutically effective amount of a pharmaceutical composition comprising pharmaceutically effective amounts of the following active ingredients:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, with the proviso that the composition does not include the composition wherein the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-imidazol-5-carboxylate and the calcium channel blocker is amlodipine or amlodipine besylate.

A method for the prevention and/or treatment of a disease caused by hypertension comprising administering to a mammal in need thereof a pharmaceutically effective amount of a pharmaceutical composition comprising pharmaceutically effective amounts of the following active ingredients:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, with the proviso that the composition does not include the composition wherein the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-imidazol-5-carboxylate and the calcium channel blocker is amlodipine or amlodipine besylate.

A method for the prevention and/or treatment of a disease selected from the group consisting of a heart disease, angina pectoris, myocardial infarction, arrhythmia, heart failure, cardiac hypertrophy, a renal disease, diabetic nephropathy, glomerulonephritis, nephrosclerosis, a cerebrovascular disease, cerebral infarction and cerebral hemorrhage comprising administering to a mammal in need thereof a pharmaceutically effective amount of a pharmaceutical composition comprising pharmaceutically effective amounts of the following active ingredients:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, with the proviso that the composition does not include the composition wherein the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-imidazol-5-carboxylate and the calcium channel blocker is amlodipine or amlodipine besylate.

A method for the prevention of restenosis following percutaneous coronary intervention or sudden death comprising administering to a mammal in need thereof a pharmaceutically effective amount of a pharmaceutical composition comprising pharmaceutically effective amounts of the following active ingredients:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, with the proviso that the composition does not include the composition wherein the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-imidazol-5-carboxylate and the calcium channel blocker is amlodipine or amlodipine besylate.

A method for the inhibition of vascular smooth muscle cells, the inhibition of neointima formation of blood vessels or the inhibition of vascular remodeling comprising administering to a mammal in need thereof a pharmaceutically effective amount of a pharmaceutical composition comprising pharmaceutically effective amounts of the following active ingredients:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, with the proviso that the composition does not include the composition wherein the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-imidazol-5-carboxylate and the calcium channel blocker is amlodipine or amlodipine besylate.

A method for the prevention and/or treatment of arteriosclerosis comprising administering to a mammal in need thereof pharmaceutically effective amounts of:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, wherein the angiotensin II receptor antagonist and the calcium channel blocker are administered separately at the same time or at a certain interval, with the proviso that if the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazol-5-carboxylate, then the calcium channel blocker is not amlodipine or amlodipine besylate.

A method for the prevention and/or treatment of hypertension comprising administering to a mammal in need thereof pharmaceutically effective amounts of:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, wherein the angiotensin II receptor antagonist and the calcium channel blocker are administered separately at the same time or at a certain interval, with the proviso that if the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazol-5-carboxylate, then the calcium channel blocker is not amlodipine or amlodipine besylate.

A method for the prevention and/or treatment of a disease caused by hypertension comprising administering to a mammal in need thereof pharmaceutically effective amounts of:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, wherein the angiotensin II receptor antagonist and the calcium channel blocker are administered separately at the same time or at a certain interval, with the proviso that if the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazol-5-carboxylate, then the calcium channel blocker is not amlodipine or amlodipine besylate.

A method for the prevention and/or treatment of a disease selected from the group consisting of a heart disease, angina pectoris, myocardial infarction, arrhythmia, heart failure, cardiac hypertrophy, a renal disease, diabetic nephropathy, glomerulonephritis, nephrosclerosis, a cerebrovascular disease, cerebral infarction and cerebral hemorrhage comprising administering to a mammal in need thereof pharmaceutically effective amounts of:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, wherein the angiotensin II receptor antagonist and the calcium channel blocker are administered separately at the same time or at a certain interval, with the proviso that if the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazol-5-carboxylate, then the calcium channel blocker is not amlodipine or amlodipine besylate.

A method for the prevention of restenosis following percutaneous coronary intervention or sudden death comprising administering to a mammal in need thereof pharmaceutically effective amounts of:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, wherein the angiotensin II receptor antagonist and the calcium channel blocker are administered separately at the same time or at a certain interval, with the proviso that if the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]imidazol-5-carboxylate, then the calcium channel blocker is not amlodipine or amlodipine besylate.

A method for the inhibition of vascular smooth muscle cells, the inhibition of neointima formation of blood vessels or the inhibition of vascular remodeling comprising administering to a mammal in need thereof pharmaceutically effective amounts of:

• (A) an angiotensin II receptor antagonist selected from the group consisting of a compound having a formula (I), a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt thereof, said compound having the following formula:
• and (B) a calcium channel blocker selected from the group consisting of a 1,4-dihydropyridine compound and a pharmacologically acceptable salt thereof, wherein the angiotensin II receptor antagonist and the calcium channel blocker are administered separately at the same time or at a certain interval, with the proviso that if the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazol-5-carboxylate, then the calcium channel blocker is not amlodipine or amlodipine besylate.