PHARMACEUTICAL COMPOSITIONS FOR PREVENTION OF OVERDOSE OR ABUSE

• US 20110046226A1
• Filed: 09/13/2010
• Published: 02/24/2011
• Est. Priority Date: 08/22/2001
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Shire LLC (Shire plc)
• Inventors: Mickle, Travis, Krishnan, Suma, Moncrief, James Scott, Lauderback, Christopher
• Granted Patent: US 8,343,927 B2
• Time in Patent Office: Days
• US Class Current: 514/626
• 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 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: C07K 5/06086 with the first amino acid being basic
• CPC Class Codes: C07K 5/0808 the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C07K 5/1008 the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids

Abstract

The invention relates to pharmaceutical compositions comprised of a chemical moiety attached to an active agent in a manner that substantially decreases the potential of the active agent to cause overdose or to be abused. When delivered at the proper dosage the pharmaceutical composition provides therapeutic activity similar to that of the parent active agent.

Claims

1-61. -61. (canceled)

62. A method of treating attention deficit hyperactivity disorder in a patient in need thereof, comprising orally administering an effective amount of an amphetamine (1-phenylpropan-2-amine) covalently bound to a chemical moiety, wherein the chemical moiety is a non-standard amino acid, the amino acid is bound through its C-terminus to the amino group of the amphetamine, and the bound amphetamine maintains a steady-state serum release curve which provides a therapeutically effective bioavailability of the amphetamine.

63. The method of claim 62, wherein the non-standard amino acid is homoserine.

64. The method of claim 62, wherein the non-standard amino acid is ornithine.

65. The method of claim 62, wherein the non-standard amino acid is sarcosine.

66. The method of claim 62, wherein the amphetamine is dextroamphetamine.

67. The method of claim 62, wherein the bound amphetamine is administered in an oral dosage form.

68. The method of claim 67, wherein the oral dosage form comprises from 5 to 500 mg of the bound amphetamine.

69. The method of claim 68, wherein the oral dosage form comprises from 10 to 250 mg of the bound amphetamine.

70. The method of claim 67, wherein the oral dosage form provides a therapeutically bioequivalent AUC of the amphetamine when compared to the AUC of the amphetamine when administered in a form in which the amphetamine is not covalently bonded to a non-standard amino acid.

71. The method of claim 67, wherein the patient is administered an oral dosage form of the bound amphetamine once daily.

72. The method of claim 62, wherein the administration of the bound amphetamine does not result in spiking blood serum concentrations of amphetamine.

73. The method of claim 62, wherein the administration of the bound amphetamine does not result in euphoria.

74. A method of treating attention deficit hyperactivity disorder in a patient in need thereof, comprising orally administering an effective amount of an amphetamine (1-phenylpropan-2-amine) covalently bound to a chemical moiety, wherein the chemical moiety is a non-standard amino acid and the amino acid is bound through its C-terminus to the amino group of the amphetamine.

75. The method of claim 74, wherein the amphetamine is dextroamphetamine.

76. The method of claim 74, wherein the bound amphetamine is administered in an oral dosage form, and the oral dosage form comprises from 5 to 500 mg of the bound amphetamine.

77. The method of claim 76, wherein the oral dosage form provides a therapeutically bioequivalent AUC of the amphetamine when compared to the AUC of the amphetamine when administered in a form in which the amphetamine is not covalently bonded to a non-standard amino acid.

78. The method of claim 74, wherein the patient is administered an oral dosage form of the bound amphetamine once daily.

79. The method of claim 74, wherein the administration of the bound amphetamine does not result in spiking blood serum concentrations of amphetamine.

80. The method of claim 74, wherein the administration of the bound amphetamine does not result in euphoria.