POLYSUBUNIT OPIOID PRODRUGS RESISTANT TO OVERDOSE AND ABUSE

摘要

The invention provides compositions and methods for the treatment or prevention of pain. The invention provides constructs whereby hydrolysis of the construct by a specified gastrointestinal enzyme directly, or indirectly, releases an opioid when taken orally as prescribed. The gastrointestinal enzyme mediated release of opioid from constructs of the invention is designed to be attenuated in vivo via a saturation or inhibition mechanism when overdoses are ingested. The invention further provides constructs that are highly resistant to oral overdose, chemical tampering, and abuse via non-oral routes of administration.

主权项

1. A composition comprising at least one GI enzyme-labile opioid releasing subunit capable of releasing an opioid agonist upon the action of a GI enzyme, wherein the at least one GI enzyme-labile opioid agonist releasing subunit is covalently linked to at least one non-opioid agonist releasing GI enzyme subunit capable of being cleaved by said GI enzyme.