Transdermal administration of ace inhibitors

Abstract

Disclosed is a dermal composition comprising enalapril ethyl ester or another prodrug corresponding to a pharmaceutically active form of an ACE inhibitor in an amount corresponding to a therapeutically effective amount of enalaprilat (or other pharmaceutically active form of enalapri) or pharmaceutically active form of the ACE inhibitor in admixture with a pharmaceutically acceptable carrier. In a preferred embodiment, the carrier is a pressure-sensitive adhesive matrix comprising a polymer or polymer blend. The dermal composition is applied in a method of substantially increasing the flux of enalaprilat through the skin of a human or an animal by maintaining the dermal composition in contact with the skin.

1 - 8 . (canceled)  
     
     
         9 . A dermal composition comprising a therapeutically effective amount of enalapril ethyl ester in admixture with a pharmaceutically acceptable carrier.  
     
     
         10 . The dermal composition according to  claim 9  wherein said carrier comprises a pressure-sensitive adhesive.  
     
     
         11 . The dermal composition according to  claim 10  wherein said pressure-sensitive adhesive is a polymer or mixture of a plurality of polymers.  
     
     
         12 . The dermal composition according to  claim 9  wherein said carrier is a flexible, finite polymer that comprises at least one of an acrylic-based polymer and a silicon-based polymer.  
     
     
         13 . The dermal composition according to  claim 9  wherein said composition further comprises an enhancer.  
     
     
         14 . The dermal composition according to  claim 13  wherein enhancer comprises dipropylene glycol and oleyl alcohol.  
     
     
         15 . A method of making the dermal composition of  claim 9 , comprising forming a mixture of enalapril ethyl ester and a pharmaceutically acceptable carrier.  
     
     
         16 . A method of treating a human being or animal suffering from a condition for which an ACE (angiotensin-converting enzyme) inhibitor is indicated, said method comprising the steps of: 
 applying to the skin of a human being or animal, the dermal composition of  claim 9;  and    maintaining said dermal composition in contact with said skin for a time sufficient to administer a therapeutically effective amount of enalaprilat.    
     
     
         17 . The method of  claim 16  wherein said condition is one selected from the group consisting of hypertension, heart failure, myocardial infarction, and nephropathy.  
     
     
         18 . A method of transdermally administering a therapeutically effective amount of an ACE inhibitor through the skin of a patient, said method comprising the steps of: 
 a) applying to the skin of said patient a dermal composition comprising a lipophilic prodrug in an amount corresponding to a therapeutically effective amount of a pharmaceutically active form of an ACE inhibitor in admixture with a pharmaceutically acceptable carrier; and    b) maintaining said dermal composition in contact with said skin for a time sufficient to deliver a therapeutically effective amount of the drug,    wherein said method is characterized in that the flux of said lipophilic prodrug is greater than that of the pharmaceutically active form of the ACE inhibitor, and wherein the ACE inhibitor is one selected from the group consisting of benazepril, lisinopril, perindopril, quinapril, ramipril, spirapril, temocapril, and trandolapril.    
     
     
         19 . The method according to  claim 18  wherein the flux of the lipophilic prodrug and the flux of the pharmaceutically active form of the ACE inhibitor are in a ratio of 100:1 to 3:1.  
     
     
         20 . The method according to  claim 19  wherein said ratio is 70:1 to 10:1.  
     
     
         21 . The method according to  claim 18  wherein said carrier comprises a pressure-sensitive adhesive.  
     
     
         22 . The method according to  claim 21  wherein said pressure-sensitive adhesive is a polymer or a mixture of a plurality of polymers.  
     
     
         23 . The method according to  claim 18  wherein said carrier is a flexible, finite polymer that comprises at least one of an acrylic-based polymer and a silicon-based polymer.  
     
     
         24 . The method according to  claim 18  wherein said dermal composition further comprises an enhancer.  
     
     
         25 . The method according to  claim 24  wherein said enhancer comprises dipropylene glycol and oleyl alcohol.  
     
     
         26 . A dermal composition comprising a lipophilic prodrug in an amount corresponding to a therapeutically effective amount of a pharmaceutically active form of an ACE inhibitor admixture with a pharmaceutically acceptable carrier, wherein the lipophilic prodrug is of the pharmaceutically active form of an ACE inhibitor selected from the group consisting of benazepril, lisinopril, perindopril, quinapril, ramipril, spirapril, temocapril, and trandolapril.  
     
     
         27 . The dermal composition according to  claim 26  wherein said carrier comprises a pressure-sensitive adhesive.  
     
     
         28 . The dermal composition according to  claim 27  wherein said pressure-sensitive adhesive is a polymer or mixture of a plurality of polymers.  
     
     
         29 . The dermal composition according to  claim 26  wherein said carrier is a flexible, finite polymer that comprises at least one of an acrylic-based polymer and a silicon-based polymer.  
     
     
         30 . The dermal composition according to  claim 26  wherein said composition further comprises an enhancer.  
     
     
         31 . The dermal composition according to  claim 26  wherein enhancer comprises dipropylene glycol and oleyl alcohol.  
     
     
         32 . A method of making the dermal composition of  claim 26 , comprising forming a mixture of the drug and a pharmaceutically acceptable carrier.  
     
     
         33 . A method of treating a human being or animal suffering from a condition for which an ACE (angiotensin-converting enzyme) inhibitor is indicated, said method comprising the steps of: 
 applying to the skin of a human being or animal, the dermal composition of  claim 26;  and    maintaining said dermal composition in contact with said skin for a time sufficient to administer a therapeutically effective amount of enalaprilat.    
     
     
         34 . The method of  claim 33  wherein said condition is one selected from the group consisting of hypertension, heart failure, myocardial infarction, and nephropathy.  
     
     
         35 . A method of transdermally administering a therapeutically effective amount of a pharmaceutically effective form of enalapril through the skin of a patient, said method comprising the steps of: 
 a) applying to the skin of said patient a dermal composition comprising enalapril ethyl ester in an amount corresponding to a therapeutically effective amount of a pharmaceutically active form of enalapril in admixture with a pharmaceutically acceptable carrier; and    b) maintaining said dermal composition in contact with said skin for a time sufficient to deliver a therapeutically effective amount of a pharmaceutically active form of enalapril,    said method characterized in that the flux of enalapril ethyl ester is greater than that of enalapril maleate.