Abuse-resistant hydrocodone compounds

• US 7,338,939 B2
• Filed: 09/30/2004
• Issued: 03/04/2008
• Est. Priority Date: 09/30/2003
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Inventors: Mickle, Travis, Moncrief, James Scott, Miller, Christal, Krishnan, Suma, Lauderback, Christopher
• Primary Examiner(s): Tsang; Cecilia J.
• Assistant Examiner(s): Audet; Maury
• Application Number:
  US10/953,110
• Publication Number:
  US 20050266070A1
• Time in Patent Office: 1,251 Days
• Field of Search: 514/9
• US Class Current: 514/1.3
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• 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

Abstract

The present invention decreases the potential for abuse of opioids, particularly hydrocodone, by covalent modification. The invention provides methods of delivering hydrocodone as conjugates that release the hydrocodone following oral administration while being resistant to abuse by circuitous routes such as intravenous (“shooting”) injection 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 comprising hydrocodone, or a pharmaceutically acceptable salt thereof, covalently attached at the 6'"'"' position to the C-terminus of a peptide wherein said peptide is Glu-Glu-Phe-Phe-Ile [SEQ ID NO:

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

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

4], or Tyr-Tyr-Ile.

7. A method of treating acute or chronic pain comprising administering to a patient the compound of claim 1 or 2.

8. The method of claim 7 wherein said compound is formulated into a tablet, a capsule, an oral solution, or an oral suspension.

10. The method of claim 8 wherein said compound is in tablet form.

11. The method of claim 8 wherein said compound is in capsule form.

2. A compound comprising hydrocodone, or a pharmaceutically acceptable salt thereof, covalently attached at the 6'"'"' position to the C-terminus of Tyr-Tyr-Phe-Phe-Ile [SEQ ID NO:

4].

3. A composition comprising hydrocodone, or a pharmaceutically acceptable salt thereof, covalently attached at the 6'"'"' position to the C-terminus of Tyr-Tyr-Phe-Phe-Ile [SEQ ID NO:

4] and at least one pharmaceutically acceptable excipient.

5. The composition of claim 3 or 4 wherein said composition is in tablet, capsule, oral solution, or oral suspension dosage form.

6. A method of treating acute or chronic pain comprising administering to a patient the composition of claim 3 or 4.

9. The composition of claim 5 wherein said composition is in tablet or capsule dosage form.

4. A composition consisting essentially of hydrocodone, or a pharmaceutically acceptable salt thereof, covalently attached at the 6'"'"' position to the C-terminus of Tyr-Tyr-Phe-Phe-Ile [SEQ ID NO:

4] and at least one pharmaceutically acceptable excipient.