Transdermally deliverable opioid prodrugs, abuse-resistant compositions and methods of using opioid prodrugs
View Patent ↗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.
1. A compound selected from the group consisting of:
2. A pharmaceutical composition comprising:
(a) a buprenorphine prodrug selected from the group consisting of:
(b) a pharmaceutical excipient.
3. The pharmaceutical composition of claim 2 further comprising a second compound selected from the group consisting of naltrexone and prodrugs of naltrexone.
4. The pharmaceutical composition of claim 2 further comprising 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 pharmaceutical composition of claim 2 further comprising 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.
6. A method of treating a medical condition in a mammal selected from the group consisting of: opioid dependence, alcohol dependence and pain comprising the step of transdermally administering to the mammal a buprenorphine prodrug from the group consisting of:
7. The method of claim 6 further comprising the step of transdermally administering to the mammal 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 .
8. The method of claim 6 further comprising the step of transdermally administering a second compound to the mammal 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.
9. A method of transdermally administering a buprenorphine prodrug to a mammal comprising the steps of:
(a) selecting a compound from the group consisting of:
(b) combining a compound selected in step (a) with a pharmaceutically acceptable excipient to form a pharmaceutical composition; and
(c) contacting the pharmaceutical composition formed in step (b) with the skin of the mammal.
10. 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.