Claims
- 1. A Factor VIII composition formulated without adding albumin to said composition, comprising the following formulation excipients in addition to Factor VIII:
4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine, 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mm to 5 mm calcium salt;, 100 mm to 300 mm NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8.
- 2. The Factor VIII composition of claim 1, additionally comprising a surfactant.
- 3. The Factor VIII composition of claim 2, wherein said surfactant is selected from the group consisting of polysorbate 20, polysorbate 80, Pluronic F68, and Brij 35.
- 4. The Factor VIII composition of claim 3, wherein said surfactant is polysorbate 80, and wherein said polysorbate 80 is present in an amount of less than 0.1%.
- 5. The Factor VIII composition of claim 1, wherein said surfactant is present in an amount of about 0.03%.
- 6. The Factor VIII composition of claim 1, wherein said buffering agent is selected from the group consisting of Tris, BIS-Tris Propane, histidine, PIPES, MOPS, HEPES, MES and ACES.
- 7. The Factor VIII composition of claim 6, wherein said buffering agent comprises Tris.
- 8. The Factor VIII composition of claim 7, wherein the Tris is present in an amount of about 20 mM.
- 9. The Factor VIII composition of claim 1, wherein said buffering agent comprises between about 10 mM and about 50 mM histidine.
- 10. The Factor VIII composition of claim 9, wherein the histidine is present in an amount of about 25 mM.
- 11. The Factor VIII composition of claim 1, further comprising an antioxidant.
- 12. The Factor VIII composition of claim 11, wherein said antioxidant is glutathione.
- 13. The Factor VIII composition of claim 12, wherein said glutathione is present in an amount of between about 0.05 mg/ml and about 1.0 mg/ml.
- 14. The Factor VIII composition of claim 1, wherein said bulking agent is present in an amount of about 8%.
- 15. The Factor VIII composition of claim 1, wherein said bulking agent is mannitol.
- 16. The Factor VIII composition of claim 1, wherein said bulking agent is glycine.
- 17. The Factor VIII composition of claim 1, wherein said stabilizing agent is present in an amount of about 2%.
- 18. The Factor VIII composition of claim 1, wherein said stabilizing agent is sucrose.
- 19. The Factor VIII composition of claim 1, wherein said stabilizing agent is, arginine.
- 20. The Factor VIII composition of claim 1, wherein said stabilizing agent is trehalose.
- 21. The Factor VIII composition of claim 1, wherein said NaCl is present in an amount of from about 200 mM to about 250 mM.
- 22. The Factor VIII composition of claim 1, wherein said NaCl is present in an amount of about 225 mM.
- 23. The Factor VIII composition of claim 1, wherein said calcium salt is calcium chloride.
- 24. The Factor VIII composition of claim 1, wherein said composition is in lyophilized form.
- 25. A Factor VIII composition formulated without adding albumin to said composition, comprising the following formulation excipients in addition to Factor VIII:
2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinmose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8.
- 26. The Factor VIII composition of claim 25, comprising about 4% hydroxyethyl starch.
- 27. The Factor VIII composition of claim 25, comprising about 200 mM NaCl.
- 28. The Factor VIII composition of claim 25, wherein said stabilizing agent is present in an amount of about 2%.
- 29. The Factor VIII composition of claim 25, wherein said stabilizing agent is sucrose.
- 30. The Factor VIII composition of claim 25, wherein said stabilizing agent is arginine.
- 31. The Factor VIII composition of claim 25, wherein said stabilizing agent is trehalose.
- 32. A Factor VIII composition formulated without adding albumin to said composition, comprising the following formulation excipients in addition to Factor VIII:
300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent for maintaining a pH of approximately between 6 and 8.
- 33. The composition of claim 32, wherein the NaCl is present in an amount of about 400 mM.
- 34. An improved method of lyophilizing an aqueous pharmaceutical formulation containing a crystallizable bulking agent and NaCl, wherein said method comprises the steps of:
(a) freezing the aqueous pharmaceutical formulation at a temperature of less than about −35° C.; (b)) annealing the pharmaceutical formulation at between about −30° and −19° C.; (c) lowering the temperature of the pharmaceutical formulation to less than about −50° C.; (d) annealing the pharmaceutical formulation at between about −30° C. and −39° C., and then (e) freeze-drying the pharmaceutical formulation.
Parent Case Info
[0001] This application is a continuation-in-part of copending U.S. patent application Ser. No. 09/255,279, filed Feb. 22, 1999, which is a continuation-in-part of copending U.S. patent application Ser. No. 09/452,752, filed Dec. 1, 1999. The entire contents of both of these applications are hereby incorporated by reference.
Continuations (1)
|
Number |
Date |
Country |
Parent |
09507011 |
Feb 2000 |
US |
Child |
10610723 |
Jul 2003 |
US |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
09452752 |
Dec 1999 |
US |
Child |
09507011 |
Feb 2000 |
US |
Parent |
09255279 |
Feb 1999 |
US |
Child |
09452752 |
Dec 1999 |
US |