Alpha-hydroxy carboxylic acid and derivatives and other GRAS-based prodrugs of opioids and uses thereof

• US 10,449,190 B2
• Filed: 03/29/2017
• Issued: 10/22/2019
• Est. Priority Date: 04/27/2015
• Status: Active Grant

• Current Assignee: John K. Thottathil
• Original Assignee: John K. Thottathil
• Inventors: Thottathil, John K.
• Primary Examiner(s): Tran, My-Chau T.
• Application Number:
  US15/472,758
• Publication Number:
  US 20170196851A1
• Time in Patent Office: 937 Days
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: C07D 489/02 with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
• CPC Class Codes: C07D 489/12 the bridge containing only two carbon atoms

Abstract

The invention describes pharmaceutical compounds and compositions comprised of a ligand attached to opioids 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.

Claims

1. An opioid prodrug of any of the following formulae where the prodrug moiety X is attached covalently to the opioid molecule,

2. The opioid prodrug of claim 1 wherein the opioid is hydrocodone, hydromorphone, morphine, codeine, dihydrocodeine, or buprenorphine.

3. The opioid prodrug of claim 2 wherein the prodrug moiety X is chemically/covalently attached to hydrocodone or hydromorphone at their 6^th position oxygen atoms as a ketone enolate ester.

6. An oral pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

8. A method of treating pain comprising orally administering the composition of claim 6 to a patient.

9. The opioid prodrug of claim 1, wherein X is malic acid.

10. The opioid prodrug of claim 1, wherein the opioid is hydrocodone.

11. The opioid prodrug of claim 1, wherein X is malic acid and the opioid is hydrocodone.

4. An opioid prodrug compound of formula

5. A pharmaceutical composition comprising one or more of the opioid prodrugs according to claim 4 and one or more pharmaceutically acceptable excipient.

7. The pharmaceutical composition of claim 4, wherein the compound is a pharmaceutically acceptable salt form.

12. The opioid prodrug compound of claim 4, wherein the opioid prodrug compound of formula