Sustained release pharmaceutical compounds to prevent abuse of controlled substances

• US 7,622,441 B2
• Filed: 08/23/2004
• Issued: 11/24/2009
• Est. Priority Date: 02/22/2002
• Status: Expired due to Fees

• Current Assignee: Shire LLC (Shire plc)
• Original Assignee: Shire LLC (Shire plc)
• Inventors: Krishnan, Suma, Mickle, Travis, Piccariello, Thomas, Moncrief, James Scott, Lauderback, Christopher
• Primary Examiner(s): AUDET, MAURY A
• Application Number:
  US10/923,257
• Publication Number:
  US 20050080012A1
• Time in Patent Office: 1,919 Days
• Field of Search: 514/12
• US Class Current: 514/1.1
• 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:

codeine; and

a carrier covalently bound to the codeine in a manner that renders the codeine pharmacologically inactive or provides reduced pharmacological activity compared to codeine alone when administered parenterally, but provides pharmacologically effective amounts of codeine when administered orally;

wherein the carrier is a peptide selected from the group consisting of Gly-Gly-Leu, Gly-Gly-Glu, Gly-Gly-Ile, Gly-Gly-Phe, Gly-Leu-Ile, Gly-Phe-Ile, Gly-Leu-Leu, Gly-Phe-Leu, Leu-Pro-Glu, Leu-Pro-Leu, Leu-Pro-Phe, Pro-Pro-Glu, Pro-Pro-Leu, Pro-Pro-Ile, Pro-Pro-Phe, Glu-Glu-Glu, Leu-Leu-Glu, Leu-Leu-Leu, Gly₄-Leu (SEQ ID NO;

     1), Glu₅ (SEQ ID NO;

     2), Gly₄-Ile (SEQ ID NO;

     3), Gly₄-Phe (SEQ ID NO;

     5), Glu₂-Gly₂ (SEQ ID NO;

     6), Glu₂-Gly₂-Leu (SEQ ID NO;

     8), or Glu2-Gly2-Ile (SEQ ID NO;

     9);

wherein the hydroxyl group of codeine is bound to the C-terminus of the carrier.

2. The composition of claim 1, wherein said composition is in tablet, a capsule, an oral suspension or an oral solution.