Compounds and compositions for prevention of overdose of oxycodone

• US 20070066537A1
• Filed: 09/30/2004
• Published: 03/22/2007
• Est. Priority Date: 02/22/2002
• Status: Abandoned Application

• Current Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Original Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Inventors: Piccariello, Thomas, Krishnan, Suma, Mickle, Travis, Lauderback, Christopher, Bera, Sanjib, Guenther, Sven, Hirschelman, Wendy, Moncrief, James
• Application Number:
  US10/953,111
• Publication Number:
  US 20070066537A1
• Time in Patent Office: Days
• US Class Current: 514/200
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• 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: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0043 Nose

Abstract

The invention relates to pharmaceutical compounds and compositions comprised of a chemical moiety attached to an opioid such as oxycodone in a manner that substantially decreases the potential of the opioid to cause overdose. When delivered at the proper dosage the pharmaceutical composition provides therapeutic activity similar to that of the parent active agent. Further the compounds and compositions of the invention are useful in preventing addiction and susceptibility to addiction.

Claims

1. A composition comprising:

a disubstituted oxycodone covalently attached at the 6′

position to a carrier peptide and covalently attached at the 14′

position to a carrier peptide wherein each said carrier peptide comprises 12 or fewer amino acids and wherein said composition is in a form suitable for oral delivery and release of said oxycodone into the bloodstream of a subject to whom the composition is to be administered.

2. The composition of claim 1, wherein at least one carrier peptide is a dipeptide.

3. The composition of claim 1, wherein at least one carrier peptide is a tripeptide.

4. The composition of claim 1, wherein at least one carrier peptide is a tetrapeptide.

5. The composition of claim 1, wherein at least one carrier peptide is a pentapeptide.

6. The composition of claim 1, wherein at least one carrier peptide is a hexapeptide.

7. The composition of any one of claims 1-6 wherein each carrier peptide comprises naturally occurring amino acids.

8. The composition of any one of claims 1-6 wherein each carrier peptide consists essentially of naturally occurring amino acids.

10. The composition of claim 1, wherein each carrier peptide is independently Ser-Ser, PolySer, Lys, -Glu-Glu, Asp-Asp, Asp-Asp-Asp, Asp-Asp-Glu, Asp-Asp-Ser, Asp-Asp-Lys, Asp-Asp-Cys, Ala-Glu, Ala-Ser, Ala-Asp, Ala-Asn, Ala-Thr, Ala-Arg, Ala-Cys, Ala-Gln, Ala-Tyr, Leu-Glu, Leu-Ser, Leu-Asp, Leu-Asn, Leu-Thr, Leu-Arg, Leu-Cys, Leu-Gln, Leu-Tyr, Phe-Glu, Phe-Ser, Phe-Asp, Phe-Asn, Phe-Thr, Phe-Arg, Phe-Cys, Phe-Gln, Phe-Tyr, Val-Glu, Val-Ser, Val-Asp, Val-Asn, Val-Thr, Val-Arg, Val-Cys, Val-Gln, Val-Tyr, Leu, Ala-Pro, Gly-Gly-Leu, Gly-Gly-Gly-Gly-Leu [SEQ ID NO:

8], Glu-Glu-Phe-Phe-Phe-Ile [SEQ ID NO;

6], Glu-Glu-Phe-Phe-Phe [SEQ ID NO;

2], Try-Try-Ile, Asp-Asp-Ile, Tyr-Tyr-Phe-Phe-Ile [SEQ ID NO;

3], Glu-Glu-Phe-Phe-Ile [SEQ ID NO;

1], Gly-Glu-Val, Pro-Glu-Val, Glu-Pro-Val, Ser-Gly-Val, Glu-Tyr-Val, Gly-Tyr-Val, Ile-Tyr-Val, Leu-Tyr-Val, or Pro-Pro-Leu.

11. The composition of claim 1, wherein each carrier peptide is independently Gly-Glu-Val, Pro-Glu-Val, Glu-Pro-Val, Ser-Gly-Val, Glu-Tyr-Val, Gly-Tyr-Val, Ile-Tyr-Val, Leu-Tyr-Val, or Pro-Pro-Leu.

13. The composition of claim 1, wherein each carrier peptide is a single amino acid.

17. The composition of any one of claims 1-6, wherein said form suitable for oral delivery is a tablet, capsule, caplet, an oral suspension or an oral solution.

18. The composition of claim 7, wherein said form suitable for oral delivery is a tablet, capsule, caplet, an oral suspension or an oral solution.

19. The composition of claim 8, wherein said form suitable for oral delivery is a tablet, capsule, caplet, an oral suspension or an oral solution.

27. The composition of claim 1, wherein each carrier peptide is Glu-Pro-Val.

28. The composition of claim 1, wherein each carrier peptide is Glu-Tyr-Val.

29. The composition of claim 1, wherein each carrier peptide is Ile-Tyr-Val.

30. The composition of any one of claims 27-29, wherein said composition is in a form suitable for oral delivery and said form is a tablet, a capsule, a caplet, an oral suspension or an oral solution.

34. A method of treating pain comprising administering the composition of claim 1.

9. (canceled)

12. (canceled)

14-16. -16. (canceled)

20-26. -26. (canceled)

31. The compound di(glutamyl-prolinyl-valine)-6,14-O,O-oxycodone.

32. The compound di(glutamyl-tyrosinyl-valine)-6,14-O,O-oxycodone

33. The compound di(isoleucinyl-tyrosinyl-valine)-6,14-O,O-oxycodone.