Stable preparation for the treatment of blood coagulation disorders

• US 6,017,891 A
• Filed: 09/05/1997
• Issued: 01/25/2000
• Est. Priority Date: 05/06/1994
• Status: Expired due to Fees

• Current Assignee: Baxter AG (Baxter International Inc.)
• Original Assignee: Baxter AG (Baxter International Inc.)
• Inventors: Turecek, Peter, Eibl, Johann, Siekmann, Juergen, Schwarz, Hans Peter
• Primary Examiner(s): TRAVERS, RUSSELL S
• Application Number:
  US08/924,533
• Time in Patent Office: 872 Days
• Field of Search: 514/21, 514/78, 424/450
• US Class Current: 424/450
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12N 9/6424 Serine endopeptidases (3.4.21)
• CPC Class Codes: C12N 9/96 Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates

Abstract

The invention relates to a stable preparation which comprises a protein, such as thrombin, that is bound in and/or on (i.e., to) lipid vesicles and that was treated for the inactivation of potentially present viruses. Further, the invention relates to methods for the production of a stable preparation for the treatment of blood coagulation disorders, wherein a protein is bound in and/or on lipid vesicles, and the method comprises a step in which the protein lipid complex is subjected to a treatment for the inactivation of potentially present viruses.

Claims

1. A storage-stable vesicular preparation comprising thrombin, wherein at least one thrombin molecule is bound to at least one lipid vesicle, and wherein the preparation is treated to inactivate viruses.

2. A preparation according to claim 1, wherein the preparation is heat-treated to inactivate viruses.

3. A preparation according to claim 1, wherein the thrombin molecule is bound to the lipid vesicle by a process selected from the group consisting of hydration, co-lyophilization, co-extrusion, dialysis and sonication.

4. A preparation according to claim 1, wherein the lipid vesicle is a phospholipid vesicle.

5. A preparation according to claim 1, wherein the lipid vesicle has a size of about 30 nm to about 900 nm.

6. A method of producing a storage-stable preparation comprising thrombin, wherein at least one thrombin molecule is bound to at least one lipid vesicle, comprising:

contacting thrombin molecules with a lipid vesicle dispersion or a lipid containing solution, and

binding the thrombin molecules to lipid vesicles.

7. A method according to claim 6, wherein the binding is performed by a process selected from the group consisting of hydration, co-lyophilization, co-extrusion, dialysis and sonication.

8. A method according to claim 6, further comprising inactivating any contaminating viruses in the preparation.

9. A method according to claim 8, wherein the inactivating decreases the thrombin activity by no more than 10%.

10. A method according to claim 6, wherein the lipid vesicle is a phospholipid vesicle.

11. A storage-stable preparation comprising lipid vesicles with thrombin molecules bound thereto.

12. A preparation according to claim 11, wherein the preparation is treated to inactivate viruses.

13. A preparation according to claim 12, wherein the preparation is heat-treated to inactivate viruses.

14. A preparation according to claim 11, wherein thrombin is bound to lipid vesicles by a process selected from the group consisting of hydration, co-lyophilization, co-extrusion, dialysis and sonication.

15. A preparation according to claim 11, wherein the preparation is a pharmaceutical preparation.

16. A preparation according to claim 15, wherein the preparation is formulated for topical use.

17. A preparation according to claim 15, wherein the preparation is formulated for parenteral administration.

18. A preparation according to claim 11, wherein the lipid vesicles are phospholipid vesicle.

19. A preparation according to claim 11, wherein the lipid vesicles have a size of about 30 nm to about 900 nm.

20. A preparation according to claim 11, wherein the preparation does not include stabilizers.

21. A preparation according to claim 11, wherein the preparation is frozen.

22. A preparation according to claim 11, wherein the preparation is lyophilized.

24. A method according to claim 22, wherein the binding is performed by a process selected from the group consisting of hydration, co-lyophilization, co-extrusion, dialysis and sonication.

23. A method of producing a storage-stable comprising lipid vesicles with thrombin molecules bound thereto, comprising:

contacting thrombin molecules with a lipid vesicle dispersion or a lipid containing solution, and

binding the thrombin molecules to lipid vesicles to obtain lipid vesicles with thrombin bound thereto.

25. A method according to claim 23, further comprising treating the lipid vesicles with thrombin bound thereto in order to inactivate contaminating viruses.

26. A method according to claim 25, wherein the treating decreases the thrombin activity by no more than 10%.

27. A method according to claim 23, wherein the lipid vesicle is a phospholipid vesicle.