Tolerance of 4-(4-(2-pyrrolycarbonyl)-1-piperazinyl)-3-trifluoromethyl-benzoylguanidine in intravenous administration

Abstract

The invention relates to new formulations for improving the local tolerance of intravenously administered 4 -( 4 -( 2 -pyrrolylcarbonyl)- 1 -piperazinyl)- 3 -trifluoromethyl-benzoylguanidine or one of the pharmacologically acceptable acid addition salts thereof.

1 . A pharmaceutical composition comprising 4-(4-(2-pyrrolylcarbonyl)-1-piperazinyl)-3-trifluoromethyl-benzoylguanidine, or one of the pharmacologically acceptable acid addition salts thereof, enveloped in a pharmaceutically acceptable polymer.  
   
   
       2 . A pharmaceutical composition according to  claim 1 , wherein the polymer is a poloxamer, polyvinylpyrrolidone or polysorbate.  
   
   
       3 . A pharmaceutical composition according to  claim 1 , wherein the polymer is Poloxamer 188 or PVP 17 PF.  
   
   
       4 . A pharmaceutical composition according to  claim 1 , wherein the polymer improves the local tolerance of 4-(4-(2-pyrrolylcarbonyl)-1-piperazinyl)-3-trifluoromethyl-benzoylguanidine or one of the pharmacologically acceptable acid addition salts thereof.  
   
   
       5 . A pharmaceutical composition according to  claim 1 , in a form suitable for intravenous administration.  
   
   
       6 . A pharmaceutical composition according to  claim 5 , wherein the 4-(4-(2-pyrrolylcarbonyl)-1-piperazinyl)-3-trifluoromethyl-benzoylguanidine, or one of the pharmacologically acceptable acid addition salts thereof, is present in a concentration of between 0.6 mg/ml and 40 mg/ml.  
   
   
       7 . A method for treating acute myocardial infarction in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition according to  claim 1 .  
   
   
       8 . A method for treating perioperative myocardial necrosis in a patient undergoing a coronary artery bypass operation, comprising administering to said patient a pharmaceutical composition according to  claim 1 .  
   
   
       9 . A pharmaceutical composition comprising 4-(4-(2-pyrrolylcarbonyl)-1-piperazinyl)-3-trifluoromethyl-benzoylguanidine, or one of the pharmacologically acceptable acid addition salts thereof, incorporated in mixed micelles comprising a phospholipid and a bile salt.  
   
   
       10 . A pharmaceutical composition according to  claim 9 , wherein the phospholipid is soya lecithin and the bile salt is a sodium salt of cholic acid or glycocholic acid.  
   
   
       11 . A pharmaceutical composition according to  claim 9 , wherein the phospholipid and bile salt improve the local tolerance of 4-(4-(2-pyrrolylcarbonyl)-1-piperazinyl)-3-trifluoromethyl-benzoylguanidine or one of the pharmacologically acceptable acid addition salts thereof.  
   
   
       12 . A pharmaceutical composition according to  claim 9 , in a form suitable for intravenous administration.  
   
   
       13 . A pharmaceutical composition according to  claim 12 , wherein the 4-(4-(2-pyrrolylcarbonyl)-1-piperazinyl)-3-trifluoromethyl-benzoylguanidine, or one of the pharmacologically acceptable acid addition salts thereof, is present in a concentration of between 0.6 mg/ml and 40 mg/ml.  
   
   
       14 . A method for treating acute myocardial infarction in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition according to  claim 9 .  
   
   
       15 . A method for treating perioperative myocardial necrosis in a patient undergoing a coronary artery bypass operation, comprising administering to said patient a pharmaceutical composition according to  claim 9.