Methods for storing cysteamine formulations and related methods of treatment

• US 10,328,037 B2
• Filed: 11/19/2018
• Issued: 06/25/2019
• Est. Priority Date: 11/17/2015
• Status: Active Grant

• Current Assignee: Horizon Orphan, LLC (Amgen Inc.)
• Original Assignee: Horizon Orphan, LLC (Amgen Inc.)
• Inventors: Desjardin, Michael, Johnson, Mark
• Primary Examiner(s): Palenik, Jeffrey T.
• Application Number:
  US16/195,481
• Publication Number:
  US 20190111008A1
• Time in Patent Office: 218 Days
• Field of Search: None
• 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. A method of treating 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.

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

1.

3. The method according to claim 1, 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.

4. The method according to claim 1, 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.

5. The method according to claim 1, 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.

6. The method according to claim 1, 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.

7. A method of treating 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.

8. The method according to claim 7, wherein the oral pharmaceutical composition further comprises an enteric coating, wherein the enteric coating comprises poly(methacrylic acid co-ethyl acrylate) 1:

1.

9. The method according to claim 7, 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.

10. The method according to claim 7, 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.

11. The method according to claim 7, 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.

12. The method according to claim 7, 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.

13. A method of treating 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.

14. The method according to claim 13, wherein the oral pharmaceutical composition further comprises an enteric coating, wherein the enteric coating comprises poly(methacrylic acid co-ethyl acrylate) 1:

1.

15. The method according to claim 13, 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.

16. The method according to claim 13, 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.

17. The method according to claim 13, 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.

18. The method according to claim 13, 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.

19. A method of treating 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 2-hydroxymethylthiazolidine in an amount less than 0.05% 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.

20. The method according to claim 19, wherein the oral pharmaceutical composition further comprises an enteric coating, wherein the enteric coating comprises poly(methacrylic acid co-ethyl acrylate) 1:

1.

21. The method according to claim 19, wherein the oral pharmaceutical composition contains 2-hydroxymethylthiazolidine in an amount less than 0.05% 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.

22. The method according to claim 19, wherein the oral pharmaceutical composition contains 2-hydroxymethylthiazolidine in an amount less than 0.05% 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.

23. The method according to claim 19, wherein the oral pharmaceutical composition contains 2-hydroxymethylthiazolidine in an amount less than 0.05% 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.

24. The method according to claim 19, wherein the oral pharmaceutical composition contains 2-hydroxymethylthiazolidine in an amount less than 0.05% 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.