METHODS FOR STORING CYSTEAMINE FORMULATIONS AND RELATED METHODS OF TREATMENT

• US 20190358179A1
• Filed: 05/03/2019
• Published: 11/28/2019
• Est. Priority Date: 11/17/2015
• Status: Active Grant

• Current Assignee: Horizon Orphan, LLC (Amgen Inc.), Raptor Pharmaceuticals Inc. (Amgen Inc.)
• Original Assignee: Horizon Orphan, LLC (Amgen Inc.)
• Inventors: DESJARDIN, Michael, JOHNSON, Mark
• Granted Patent: US 10,548,859 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

Methods of storing and methods of stabilizing pharmaceutical compositions comprising cysteamine, or a pharmaceutically acceptable salt thereof, are provided. Methods of distributing pharmaceutical compositions comprising cysteamine, or a pharmaceutically acceptable salt thereof, and methods of treating cystinosis also are provided.

Claims

1-92. -92. (canceled)

93. A method of treating nephropathic cystinosis in a subject in need thereof, comprising:

administering twice daily to the subject an oral pharmaceutical composition comprising cysteamine bitartrate,

wherein the oral pharmaceutical composition contains 2-hydroxythiomorpholine in an amount less than 0.5% relative to the amount of cysteamine bitartrate,

wherein the oral pharmaceutical composition was stored by a manufacturer, a distributor, a pharmacy, or a hospital at a temperature of between about 2°

C. and about 8°

C. prior to dispensing the oral pharmaceutical composition to the subject, and

wherein after the oral pharmaceutical composition is dispensed to the subject, the oral pharmaceutical composition is stored at a temperature of between about 20°

C. and about 25°

C.

94. The method according to claim 93, wherein the oral pharmaceutical composition further comprises an enteric coating wherein the enteric coating comprises poly(methacrylic acid co-ethyl acrylate) 1:

1.

95. The method according to claim 93, wherein the oral pharmaceutical composition contains 2-hydroxythiomorpholine in an amount less than 0.5% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for a period of up to 15 months.

96. The method according to claim 93, wherein the oral pharmaceutical composition contains 2-hydroxythiomorpholine in an amount less than 0.5% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 25°

C. and 60% relative humidity for a period of up to 3 months.

97. The method according to claim 93, wherein the oral pharmaceutical composition contains 2-hydroxythiomorpholine in an amount less than 0.5% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 30°

C. and 65% relative humidity for a period of up to 3 months.

98. The method according to claim 93, wherein the oral pharmaceutical composition contains 2-hydroxythiomorpholine in an amount less than 0.5% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 30°

C. and 70% relative humidity for a period of up to 3 months.

99. A method of treating nephropathic cystinosis in a subject in need thereof, comprising:

administering twice daily to the subject an oral pharmaceutical composition comprising cysteamine bitartrate,

wherein the oral pharmaceutical composition contains cystamine in an amount less than 4% relative to the amount of cysteamine bitartrate,

wherein the oral pharmaceutical composition was stored by a manufacturer, a distributor, a pharmacy, or a hospital at a temperature of between about 2°

C. and about 8°

C. prior to dispensing the oral pharmaceutical composition to the subject, and

wherein after the oral pharmaceutical composition is dispensed to the subject, the oral pharmaceutical composition is stored at a temperature of between about 20°

C. and about 25°

C.

100. The method according to claim 99, wherein the oral pharmaceutical composition further comprises an enteric coating, wherein the enteric coating comprises poly(methacrylic acid co-ethyl acrylate) 1:

1.

101. The method according to claim 99, wherein the oral pharmaceutical composition contains cystamine in an amount less than 4% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for a period of up to 15 months.

102. The method according to claim 99, wherein the oral pharmaceutical composition contains cystamine in an amount less than 4% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 25°

C. and 60% relative humidity for a period of up to 3 months.

103. The method according to claim 99, wherein the oral pharmaceutical composition contains cystamine in an amount less than 4% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 30°

C. and 65% relative humidity for a period of up to 3 months.

104. The method according to claim 99, wherein the oral pharmaceutical composition contains cystamine in an amount less than 4% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 30°

C. and 70% relative humidity for a period of up to 3 months.

105. A method of treating nephropathic cystinosis in a subject in need thereof, comprising:

administering twice daily to the subject an oral pharmaceutical composition comprising cysteamine bitartrate,

wherein the pharmaceutical composition contains cystamine tartrate amide in an amount less than 0.5% relative to the amount of cysteamine bitartrate,

wherein the oral pharmaceutical composition was stored by a manufacturer, a distributor, a pharmacy, or a hospital at a temperature of between about 2°

C. and about 8°

C. prior to dispensing the oral pharmaceutical composition to the subject, and

wherein after the oral pharmaceutical composition is dispensed to the subject, the oral pharmaceutical composition is stored at a temperature of between about 20°

C. and about 25°

C.

106. The method according to claim 105, wherein the oral pharmaceutical composition further comprises an enteric coating, wherein the enteric coating comprises poly(methacrylic acid co-ethyl acrylate) 1:

1.

107. The method according to claim 105, wherein the oral pharmaceutical composition contains cystamine tartrate amide in an amount less than 0.5% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for a period of up to 15 months.

108. The method according to claim 105, wherein the oral pharmaceutical composition contains cystamine tartrate amide in an amount less than 0.5% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 25°

C. and 60% relative humidity for a period of up to 3 months.

109. The method according to claim 105, wherein the oral pharmaceutical composition contains cystamine tartrate amide in an amount less than 0.5% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 30°

C. and 65% relative humidity for a period of up to 3 months.

110. The method according to claim 105, wherein the oral pharmaceutical composition contains cystamine tartrate amide in an amount less than 0.5% relative to the amount of cysteamine bitartrate when the oral pharmaceutical composition is stored at a temperature of between about 2°

C. and about 8°

C. for an initial period of up to 15 months, and wherein the oral pharmaceutical composition is subsequently stored at a temperature of 30°

C. and 70% relative humidity for a period of up to 3 months.