Alpha-hydroxy carboxylic acid and derivatives and other GRAS-based prodrugs of oxymorphone and uses thereof
The invention describes pharmaceutical compounds and compositions comprised of a ligand attached to the opioid oxymorphone, in a manner that substantially decreases or deters the potential for opioid abuse, addiction, illicit and illegal use, and overdose. When delivered at the proper dosage, the pharmaceutical composition provides therapeutic activity similar to that of the parent active agent.
1. An oxymorphone prodrug of the following formula where the prodrug moiety X is attached covalently to the oxymorphone molecule via the 6 position ketone enolate oxygen as the enolate ester,
or a pharmaceutically acceptable salt thereof,
wherein X is malic acid covalently attached to the oxymorphone.
2. An oxymorphone prodrug compound represented by any one of
3. A pharmaceutical composition comprising one or more of the oxymorphone prodrugs according to claim 2 and one or more pharmaceutically acceptable excipients.
4. An oral pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
5. The pharmaceutical composition of claim 4 , wherein the compound is a pharmaceutically acceptable salt form.
6. A method of treating pain comprising orally administering the composition of claim 4 to a patient.