Methods and compositions for treating hypertension, angina, and other disorders using optically pure (-) amlodipine

Abstract

Methods and compositions are disclosed utilizing the optically pure (−) isomer of amlodipine. This compound is a potent drug for the treatment of hypertension while avoiding the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. The (−) isomer of amlodipine is also useful for the treatment of angina and such other conditions as may be related to the activity of (−) amlodipine as a calcium channel antagonist such as cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure, without the concomitant liability of adverse effects associated with the racemic mixture of amlodipine.

1 - 8 . Canceled without prejudice.  
     
     
         9 . An antihypertensive composition for the treatment of a human in need of antihypertensive therapy which comprises, an amount of (−) amlodipine or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, said amount being sufficient to alleviate said hypertension, but insufficient to cause adverse affects of racemic amlodipine.  
     
     
         10 . A composition according to  claim 9  wherein the amount is about 0.01 mg to about 100.0 mg.  
     
     
         11 . A composition according to  claim 10  wherein said composition is administered from one to four times a day.  
     
     
         12 . A composition according to  claim 11  wherein said composition is administered once a day.  
     
     
         13 . A composition according to  claim 10  which comprises (−) amlodipine besylate.  
     
     
         14 . A composition according to  claim 13  wherein said composition is adapted for oral administration.  
     
     
         15 . A composition according to  claim 13  adapted for intravenous delivery.  
     
     
         16 . A composition according to  claim 13  for use in a transdermal formulation.  
     
     
         17 . A composition according to  claim 16  for use as a transdermal patch.  
     
     
         18 . The composition according to  claim 9  wherein (−) amlodipine or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, is administered together with a pharmaceutically acceptable carrier.  
     
     
         19 - 26 . Canceled without prejudice.  
     
     
         27 . An antianginal composition for the treatment of a human having angina which comprises, an amount of (−) amlodipine or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, said amount being sufficient to alleviate said angina but insufficient to alleviate said angina but insufficient to cause adverse effects of racemic amlodipine.  
     
     
         28 . A composition according to  claim 27  wherein the amount is about 0.01 mg to about 100.0 mg.  
     
     
         29 . A composition according to  claim 28  wherein said composition is administered from one to four times a day.  
     
     
         30 . A composition according to  claim 29  wherein said composition is administered once a day.  
     
     
         31 . A composition according to  claim 28  which comprises (−) amlodipine besylate.  
     
     
         32 . A composition according to  claim 31  wherein said composition is adapted for oral administration.  
     
     
         33 . A composition according to  claim 31  adapted for intravenous delivery.  
     
     
         34 . A composition according to  claim 31  for use in a transdermal formulation.  
     
     
         35 . A composition according to  claim 34  for use as a transdermal patch.  
     
     
         36 . The composition according to  claim 27  wherein (−) amlodipine or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, is administered together with a pharmaceutically acceptable carrier.  
     
     
         37 - 45 . Canceled without prejudice.  
     
     
         46 . A composition for treating a condition caused by excessive calcium influx in cells in a human which comprises an amount of (−) amlodipine or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, said amount being sufficient to alleviate said condition, but insufficient to cause adverse effects of racemic amlodipine.  
     
     
         47 . A composition according to  claim 46  wherein said condition caused by excessive calcium influx in cells in a human is selected from the group consisting of cerebral ischemia, cerebral disorders, cognitive disorders, Alzheimer's dementia, memory impairment, arrhythmias, cardiac hypertrophy, congestive heart failure, coronary vasospasm, migraine, bronchospasm and asthma, Raynaud's phenomenon, myocardial infarction, renal impairment and acute renal failure.  
     
     
         48 . A composition according to  claim 46  wherein the amount is about. 0.01 mg to about 100.0 mg.  
     
     
         49 . A composition according to  claim 48  wherein said composition is administered from one to four times a day.  
     
     
         50 . A composition according to  claim 49  wherein said composition is administered once a day.  
     
     
         51 . A composition according to  claim 48  which comprises (−) amlodipine besylate.  
     
     
         52 . A composition according to  claim 51  wherein said composition is adapted for oral administration.  
     
     
         53 . A composition according to  claim 51  adapted for intravenous.  
     
     
         54 . A composition according to  claim 51  for use in a transdermal formulation.  
     
     
         55 . A composition according to  claim 54  for use as a transdermal patch.  
     
     
         56 . The composition according to  claim 46  wherein (−) amlodipine or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer is administered together with a pharmaceutically acceptable carrier.