Sustained release pharmaceutical compounds to prevent abuse of controlled substances

• US 20050080012A1
• Filed: 08/23/2004
• Published: 04/14/2005
• Est. Priority Date: 02/22/2002
• Status: Active Grant

• Current Assignee: Shire LLC (Shire plc)
• Original Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Inventors: Piccariello, Thomas, Krishnan, Suma, Mickle, Travis, Moncrief, James Scott, Lauderback, Christopher
• Granted Patent: US 7,622,441 B2
• Time in Patent Office: Days
• US Class Current: 514/18.400
• CPC Class Codes: A61K 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides methods for altering controlled substances in a manner that decreases their potential for abuse. The novel compounds may be combined in tablets with suitable excipients or formulated in solution for oral delivery. When delivered by the oral route the controlled substance is released in a time-dependent manner (sustained release) by acid hydrolysis and/or enzymatic cleavage. When administered by injection the controlled substance is released in a time-dependent manner (sustained release) by way of serum enzymes.

Claims

1. A pharmaceutical composition comprising:

a controlled substance; and

an amino acid or polypeptide covalently bound to said controlled substance in a manner that renders said controlled substance pharmacologically inactive.

2. The composition of claim 1, wherein said controlled substance is released in active form in the presence of acid present in the stomach or in the presence of enzymes present in the intestinal tract or blood serum.

3. The composition of claim 2, adapted for oral administration, wherein said controlled substance is released in active form in the presence of acid present in the stomach or in the presence of enzymes present in the intestinal tract.

4. The composition of claim 1, wherein said polypeptide comprises less than 70 amino acids.

5. The composition of claim 1, wherein said polypeptide comprises less than 50 amino acids.

6. The composition of claim 1, wherein said polypeptide comprises less than 10 amino acids.

7. The composition of claim 1 wherein said chemical moiety is polyserine.

8. The composition of claim 1 wherein said chemical moiety is bound to said controlled substance by an ester or carbonate bond.

9. The composition of claim 1 wherein said controlled substance is codeine.

10. The composition of claim 1 wherein said controlled substance is fentanyl.

11. The composition of claim 1 wherein said controlled substance is hydrocodone.

12. The composition of claim 1 wherein said controlled substance is hydromorphone.

13. The composition of claim 1 wherein said controlled substance is levorphanol.

14. The composition of claim 1 wherein said controlled substance is methadone.

15. The composition of claim 1 wherein said controlled substance is morphine

16. The composition of claim 1 wherein said controlled substance is oxycodone.

17. The composition of claim 1 wherein said controlled substance is propoxyphene.

18. The composition of claim 1 wherein said controlled substance is sufentanyl.

19. The composition of claim 1 wherein said controlled substance is amphetamine.

20. The composition of claim 1 wherein said controlled substance is methylphenidate.

21. The composition of claim 1 wherein said chemical moiety is a polypeptide.

22. The composition of claim 1 wherein said chemical moiety is an amino acid.

23. The composition of claim 1 wherein said chemical moiety is a protein.

24. The composition of claim 3 that releases said controlled substance in a pharmacologically active form when administered to a human patient by the oral route.

25. The composition of claim 3 that is resistant to release of said controlled substance in a pharmacologically active form when administered by the intranasal route thus diminishing or preventing a euphoric effect.

26. The composition of claim 3 that is resistant to release of said controlled substance in a pharmacologically active form when administered by inhalation thus diminishing or preventing a euphoric effect.

27. A composition of claim 3 that is resistant to release of said controlled substance in a pharmacologically active form when administered by parenteral injection thus diminishing or preventing a euphoric effect.

28. A method for delivering a controlled substance to a patient so as to obtain a therapeutic, but not a substantial euphoric effect, comprising orally administering the composition of claim 1 to said patient.

29. A method for delivering a controlled substance to a patient so as to obtain a therapeutic, but not a substantial euphoric effect, comprising parenterally administering the composition of claim 1 to said patient.

30. A composition of claim 1 wherein the said chemical moiety is an oligopeptide.

31. A composition of claim 30 wherein the said oligopeptide is specifically designed to be cleaved by intestinal enzymes.