Stability for injection solutions

• US 20040235731A1
• Filed: 10/15/2003
• Published: 11/25/2004
• Est. Priority Date: 09/01/1998
• Status: Active Grant

• Current Assignee: Anna Lundgren, Mats Sundgren
• Original Assignee: Anna Lundgren, Mats Sundgren
• Inventors: Sundgren, Mats, Lundgren, Anna
• Granted Patent: US 6,998,136 B2
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: A61J 1/05 for collecting, storing or administering blood, plasma or medical fluids multiple bags systems for separating or storing blood components A61M1/0209; Infusion or perfusion containers
• CPC Class Codes: A61J 1/062 Carpules
• CPC Class Codes: A61J 1/1468 Containers characterised by specific material properties
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61M 5/3129 Syringe barrels A61M5/3205 and A61M5/50 take precedence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A primary package containing a low molecular weight peptide-based thrombin inhibitors which package is sealed with a rubber stopper or plunger containing bromobutyl rubber.

Claims

1-18. -18 (canceled)

19. A method for inhibiting thrombin in a mammal, comprising administering a therapeutically effective amount of an aqueous solution of a low molecular weight peptide-based thrombin inhibitor or a salt thereof to the mammal, wherein the solution is administered from a primary package sealed with a stopper or plunger comprising bromobutyl rubber.

20. The method according to claim 19, wherein the primary package is selected from the group consisting of vials, bottles, cartridges, and prefilled syringes.

21. The method according to claim 19, wherein the thrombin inhibitor is a gatran.

22. The method according to claim 19, wherein the thrombin inhibitor is inogatran.

23. The method according to claim 19, wherein the thrombin inhibitor is melagatran.

24. The method according to claim 19, wherein the thrombin inhibitor is (glycine, N-(1-cyclohexyl-2-[2-[[[[4-[(hydroxy-imino)-aminomethyl]-phenyl]-methyl]-amino]carbonyl]-1-azetidinyl]-2-oxoethyl]-, ethyl ester, [S-(R*, S*)]-).

25. The method according to claim 19, wherein the solution is administered parenterally.

26. The method according to claim 19, wherein the pH of the solution is in the range of about 3 to 8.

27. The method according to claim 26, wherein the pH of the solution is about 5.

28. The method according to claim 19, wherein the solution further comprises hydroxy-propyl-β

-cyclodextrin.

29. The method according to claim 19, wherein the solution fever comprises NaCl.

30. The method according to claim 19, wherein the concentration of the thrombin inhibitor in the solution is in the range of 0.001-100 mg/ml.

31. The method according to claim 30, wherein the concentration of the thrombin inhibitor in solution is the range of 2.5-20 mg/ml.

32. The method according to claim 19, wherein the bromobutyl rubber consists of, or corresponds to, the bromobutyl rubber selected from the group consisting of PH 4023/50;

W 4416/50; and

FM 257.