Compounds and compositions for prevention of overdose of oxycodone

• US 20050176644A1
• Filed: 09/30/2004
• Published: 08/11/2005
• Est. Priority Date: 09/30/2003
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Inventors: Krishnan, Suma, Mickle, Travis, Moncrief, James Scott, Lauderback, Christopher, Bera, Sanjib, Guenther, Sven, Hirschelman, Wendy
• Granted Patent: US 7,169,752 B2
• Time in Patent Office: Days
• US Class Current: 514/1.300
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence

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

1-101. -101. (canceled)

102. A method for reducing the abuse potential of an oral dosage form of an oxycodone composition comprising:

covalently bonding at the 6′

position and the 14′

position of said oxycodone a single amino acid or an oligopeptide of 12 or fewer amino acids such that the oxycodone does not release into a patient'"'"'s bloodstream at levels that give rise to a euphoric or overdose level.

104. The method of claim 102 wherein the oligopeptide is a dipeptide

105. The method of claim 102 wherein the oligopeptide is a tripeptide.

106. The method of claim 102 wherein the oligopeptide is a tetrapeptide.

107. The method of claim 102 wherein the oligopeptide is a pentapeptide.

108. The method of claim 102 wherein the oligopeptide is a hexapeptide.

109. The method of claim 102 wherein said oligopeptide consists essentially of naturally occurring amino acids.

110. The method of claim 102 wherein said oligopeptide consists of naturally occurring amino acids.

111. The method of claim 102, wherein each oligopeptide is Glu-Pro-Val.

112. The composition of claim 102, wherein each oligopeptide is Glu-Tyr-Val.

113. The composition of claim 102, wherein each oligopeptide is Ile-Tyr-Val.

114. The method of claims 102 wherein said oligopeptide is Pro-Pro-Ile, Phe-Phe-Lys-Phe-Phe [SEQ ID NO:

5], Tyr-Tyr-Lys-Tyr-Tyr [SEQ ID NO;

4], Tyr-Tyr-Phe, Phe-Phe-Leu, Phe-Phe-Val, Phe-Phe-Ile, Glu-Glu-Phe-Phe-Ile [SEQ ID NO;

1], Tyr-Tyr-Ile, Lys-Lys-Val, Asp-Asp-Val, Tyr-Tyr-Val, Pro-Pro-Val, Glu-Glu-Val, or Thr-Thr-Val.

115. The method of claim 111, wherein said oral dosage form is a tablet, a capsule, an oral solution, or an oral suspension.

116. The method of claim 112, wherein said oral dosage form is a tablet, a capsule, an oral solution, or an oral suspension.

117. The method of claim 113, wherein said oral dosage form is a tablet, a capsule, an oral solution, or an oral suspension.

103. A method for preventing abuse of oxycodone by a patient comprising providing to said patient oxycodone covalently bound at the 6′

position and the 14′

position of said oxycodone a single amino acid or an oligopeptide of 12 or fewer amino acids wherein said bound oxycodone maintains a serum release curve which provides therapeutically effective bioavailability but prevents spiking or an increase in blood serum concentrations compared to unbound oxycodone when taken at doses exceeding the therapeutically effective range.