ABUSE-RESISTANT HYDROCODONE COMPOUNDS, COMPOSITIONS AND METHODS OF USING THE SAME

• US 20080090771A1
• Filed: 10/08/2007
• Published: 04/17/2008
• Est. Priority Date: 10/06/2006
• Status: Abandoned Application

• Current Assignee: Shire LLC (Shire plc)
• Original Assignee: Shire LLC (Shire plc)
• Inventors: Moncrief, James
• Application Number:
  US11/868,636
• Publication Number:
  US 20080090771A1
• Time in Patent Office: Days
• US Class Current: 514/18.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07D 489/02 with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
• CPC Class Codes: C07K 5/0806 the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 5/0808 the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C07K 5/0812 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/0815 with the first amino acid being basic
• CPC Class Codes: C07K 5/0819 with the first amino acid being acidic
• CPC Class Codes: C07K 5/0823 and Pro-amino acid; Derivatives thereof
• CPC Class Codes: C07K 5/1008 the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 5/101 the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C07K 5/1019 with the first amino acid being basic
• CPC Class Codes: C07K 5/1021 with the first amino acid being acidic
• CPC Class Codes: C07K 5/1024 with the first amino acid being heterocyclic
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 9/001 the peptide sequence having less than 12 amino acids and not being part of a ring structure

Abstract

The invention relates to compounds, compositions and methods comprised of a chemical moiety attached to hydrocodone. The invention provides embodiments that provide a decrease in the potential of hydrocodone to cause overdose or to be abused while still delivering therapeutic activity similar to that of the parent hydrocodone. The invention also provides methods of delivering hydrocodone as conjugates that release the hydrocodone following oral administration while being resistant to abuse by other routes such as intravenous injection (“shooting”) and intranasal administration (“snorting”). Further, hydrocodone compositions of the invention are resistant to oral abuse as well, since release of the hydrocodone at suprapharmacological doses reaches saturation.

Claims

1. A compound of the formula:

2. The compound of claim 1, wherein said carrier peptide is selected from an amino acid, a dipeptide, a tripeptide, a tetrapeptide and a pentapeptide.

3. The compound of claim 1, wherein said carrier peptide is selected from acetyl-Glu-Glu-Pro-Pro-Ile, Asp-Asp-Gly-Gly-Ile, Asp-Asp-Leu-Leu-Ile, Asp-Asp-Leu-Leu-Ile, Asp-Asp-Pro-Pro-Ile, Ethyl Carbonate, galactose-Gly-Gly-Ile, galactose-Gly-Gly-Leu, galactose-Ile, Glu-Glu-Gly-Gly-Phe, Glu-Glu-Leu-Leu-Leu, Glu-Glu-Phe-Phe-Leu, Glu-Glu-Phe-Pro-Ile, Glu-Glu-Pro-Pro-Leu, Glu-Glu-Pro-Phe-Ile, Glu-Glu-Glu-Glu-Ile, Glu_pyro-Glu, Gly-Gly-Glu-Glu-Ile, Lys-Lys-Leu-Leu-Ile, Lys-Lys-Pro-Pro-Ile, Phe-Phe-Glu-Glu-Ile, Phe-Phe-Phe-Phe-Phe, Thr-Thr-Gly-Gly-Ile, Thr-Thr-Phe-Phe-Ile, Tyr-Tyr-Leu-Leu-Ile, Tyr-Tyr-Phe-Phe-Ile, Tyr-Tyr-Pro-Pro-Ile, Tyr-Tyr-Pro-Phe-Ile, Tyr-Tyr-Phe-Phe-Ile, and Glu-Glu-Phe-Phe-Phe.

4. The compound of claim 2, wherein said carrier peptide is a tripeptide selected from (D)Lys-Lys-Ile, Asp-Asp-Ile, Gln-Gln-Ile, Glu-Glu-Leu, Gly-Ile-Ile, Leu-Leu-Ile, Leu-Pro-Ile, Lys-Lys-Ile, Phe-Phe-Ile, Phe-Phe-Leu, Phe-Phe-Phe, Pro-Ile-Ile, Pro-Leu-Ile, Pro-Phe-Ile, Thr-Thr-Ile, Tyr-Tyr-Ile, Gln-Gln-Ile, Tyr-Tyr-Ile, Asp-Asp-Ile, and Pro-Pro-Leu.

5. A pharmaceutical composition comprising a compound of the formula:

6. The composition of claim 5, wherein said carrier peptide is selected from an amino acid, a dipeptide, a tripeptide, a tetrapeptide and a pentapeptide.

7. The composition of claim 5 which provides a serum release curve for hydrocodone that does not increase above the toxicity level of hydrocodone when taken at doses exceeding those within the therapeutic range for unbound hydrocodone.

8. The composition of claim 5 which maintains a steady-state serum release curve of hydrocodone that provides a therapeutically effective bioavailability but prevents spiking or increased blood serum concentrations compared to unbound hydrocodone.

9. The composition of claim 5, wherein when said composition is administered orally, bioavailability of hydrocodone or a salt thereof is maintained, but when administered intravenously or intranasally, the bioavailability of hydrocodone is decreased.

10. The composition of claim 5 which is in a form suitable for oral administration.

11. A method of treating pain, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of the formula:

12. The method of claim 11, wherein said carrier peptide is selected from an amino acid, a dipeptide, a tripeptide, a tetrapeptide and a pentapeptide.