Transdermally deliverable opioid prodrugs, abuse-resistant compositions and methods of using opioid prodrugs

Abstract

Described herein are opioid prodrugs, methods of making opioid prodrugs, formulations comprising opioid prodrugs, and methods of using opioid prodrugs. One embodiment described herein relates to the transdermal administration of a buprenorphine prodrug in an abuse-resistant formulation for treating and preventing diseases and/or disorders.

We claim: 
     
         1 . A compound having the formula: 
       
         
           
           
               
               
           
         
         wherein R 1  is selected from the group consisting of oxygenated alkyl carbonate, alkyl carbonate and oxygenated ester. 
       
     
     
         2 . A method of treating a medical condition in a mammal comprising the step of transdermally administering a buprenorphine prodrug from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 2  wherein the medical condition is selected from the group consisting of: opioid dependence, alcohol dependence and pain. 
     
     
         4 . The method of  claim 2  further comprising the step of transdermally administering a second compound having the formula: 
       
         
           
           
               
               
           
         
         wherein R 3  is selected from the group consisting of: H; —COC(CH 3 ) 3 ; —COCH(CH 3 ) 2 ; —COCH 2 CH(CH 3 ) 2 ; —COCH(CH 2 CH 3 ) 2 ; —CON(CH 2 CH 3 ) 2 ; —CON(CH(CH 3 ) 2 ) 2 ; COOCH(CH 3 ) 2 ; 
       
       
         
           
           
               
               
           
         
       
       and —CO(CH 2 ) 2 OCH 3 . 
     
     
         5 . The method of  claim 4  wherein the medical condition is selected from the group consisting of: opioid dependence; alcohol dependence and pain. 
     
     
         6 . The method of  claim 2  further comprising the step of transdermally administering a second compound selected from the group consisting of: naltrexone; 3-O-pivalyl naltrexone; 3-O-isovaleryl naltrexone; 3-O-(2′-ethylbutyryl)naltrexone; 3-O-isobutyryl naltrexone; 3-O-isopropyloxycarbonyl naltrexone; 3-O-tertiarybutyloxycarbonyl naltrexone; N,N-dimethyl-3-O-carbamate naltrexone; N,N-diethyl-3-O-carbamate naltrexone; and N,N-diisopropyl-3-O-carbamate naltrexone. 
     
     
         7 . A method for transdermally delivering a buprenorphine prodrug to a mammal comprising the steps of:
 (a) selecting a buprenorphine prodrug from the group consisting of:   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         (b) selecting a naltrexone prodrug of having the formula 
       
       
         
           
           
               
               
           
         
         wherein R 3  is selected from the group consisting of: H; —COC(CH 3 ) 3 ; —COCH(CH 3 ) 2 ; —COCH 2 CH(CH 3 ) 2 ; —COCH(CH 2 CH 3 ) 2 ; —CON(CH 2 CH 3 ) 2 ; —CON(CH(CH 3 ) 2 ) 2 ; COOCH(CH 3 ) 2 ; 
       
       
         
           
           
               
               
           
         
       
       and —CO(CH 2 ) 2 OCH 3 ;
 (c) combining the compounds selected in (a) and (b) with a pharmaceutically acceptable excipient to form a pharmaceutical composition; and 
 (d) contacting the pharmaceutical composition with the skin of the mammal.