Composition for preserving platelets and method of using the same

• US 20060177811A1
• Filed: 01/12/2006
• Published: 08/10/2006
• Est. Priority Date: 01/12/2005
• Status: Active Grant

• Current Assignee: Biovec Transfusion LLC
• Original Assignee: Biovec Transfusion LLC
• Inventors: Mousa, Shaker, Sehgal, Lakshman R.
• Granted Patent: US 7,964,338 B2
• Time in Patent Office: Days
• US Class Current: 435/2
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0215 Disinfecting agents, e.g. antimicrobials for preserving living parts
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients

Abstract

The present invention relates to compositions and methods for storing platelets to preserve the function and freshness of the platelets. More particularly, the present invention relates to the use of a preservative composition having an antiplatelet agent, an anticoagulant, and an oxygen carrier, for maintaining the freshness of platelets. Additionally, the composition may also contain an ultra-short acting broad spectrum anti-microbial agents. The preservative composition may be used to store platelets in a liquid state, a frozen state, or a freeze-dried state.

Claims

1. A platelet preservation composition, comprising:

a) an antiplatelet agent;

b) an anticoagulant; and

c) an oxygen carrier;

wherein said composition is capable of extending the shelf-life of a platelet.

2. The composition of claim 1, wherein said antiplatelet agent is capable of reversibly blocking platelet activation and/or aggregation by blocking sites on the platelet surface.

3. The composition of claim 1, wherein said antiplatelet agent is capable of binding to, or associating with a GPIIb/IIIa receptor site.

4. The composition of claim 1, wherein said antiplatelet agent is selected from the group consisting of DUP728, XJ757, XR299, eptifibatide, orbofiban, xemilofiban, Lamifiban, tirofiban (Aggrastat), and mixtures thereof.

5. The composition of claim 1, wherein said antiplatelet agent is selected from the group consisting of linear and cyclic RGD analogs.

6. The composition of claim 5, wherein said linear and cyclic RGD analogs are conjugated to a Nitric oxide donor.

7. The composition of claim 1, wherein said antiplatelet agent is a pharmaceutically acceptable antiplatelet agent and has a circulating half-life of inhibition of about less than 4 hours.

8. The composition of claim 1, wherein said antiplatelet agent comprises about 0.001 mg to about 5 mg of a GPIIb/IIIa inhibitor.

9. The composition of claim 1, wherein said anticoagulant is a compound that reversibly inhibits factor Xa, or factor IIa, or both.

10. The composition of claim 9, wherein said anticoagulant is a short-to-ultrashort acting Xa inhibitor with a circulating half-life of less than 4 hours.

11. The composition of claim 10, wherein said anticoagulant is selected from the group consisting of DX-9065a, BX-80783, RPR-120844, and short-to-ultrashort acting Xa inhibitors.

12. The composition of claim 9, wherein said anticoagulant is a short-to-ultrashort acting IIa inhibitor, and wherein said short-to-ultrashort acting IIa inhibitor is selected from the group consisting of hirudin, hirulog, melgatran, and combinations thereof.

13. The composition of claim 9, wherein said anticoagulant is a pharmaceutically acceptable anticoagulant and is a combination of at least one short-to-ultrashort acting IIa inhibitor, and at least one short-to-ultrashort acting Xa inhibitor.

14. The composition of claim 1, wherein said antiplatelet agent is a compound that binds to or associates with GPIIb/IIIa sites, and wherein the anticoagulant is a factor Xa inhibitor, a factor IIa inhibitor, or a combination of both.

15. The composition of claim 1, wherein said oxygen carrier is a pharmaceutically acceptable oxygen carrier and is selected from the group consisting of hemoglobin, ferroprotoporphyrin, perfluorochemicals, and mixtures thereof.

16. The composition of claim 15, wherein said oxygen carrier is a hemoglobin-based oxygen carrier.

17. The composition of claim 16, wherein said hemoglobin-based oxygen carrier is substantially free of red cell membrane contaminants.

18. The composition of claim 1, further comprising a short-to-ultrashort acting broad spectrum anti-microbial agent.

19. The composition of claim 18, wherein said short-to-ultrashort acting anti-microbial agent is selected from the group consisting of:

Penicillin, Natural penicillins, Semisynthetic penicillins, Monobactam, Cephalosporin Carbapenems Vancomycin, Isoniazid (INH), Ethambutol, Aminoglycoside, Tetracycline, Chloramphenicol, Macrolide, Rifamycin, Quinolone, Fluoroquinolone, Sulfonamide, Synergism, Polyene antibiotic, Imidazole, Triazole, Griseofulvin and combinations thereof.

20. A method of extending the shelf-life of platelets, comprising the steps of:

(a) admixing a preservative composition with inactivated, functional platelets to provide a preserved platelet composition; and

(b) store the preserved platelet composition in an oxygen-permeable container or an oxygen-impermeable container,

Wherein the preservative composition comprises an antiplatelet agent, an anticoagulant, and an oxygen based carrier.

21. The method of claim 20, wherein said inactivated, functional platelets are substantially free of red blood cells and other blood nutrients.

22. The method of claim 20, wherein said antiplatelet agent is a pharmaceutically acceptable antiplatelet agent and is a compound that binds to or associates with GPIIb/IIIa sites, with a short to ultra-short half life.

23. The method of claim 20, wherein said oxygen carrier is a pharmaceutically acceptable oxygen carrier and is selected from the group consisting of hemoglobin, ferroprotoporphyrin, perfluorochemicals, and mixtures thereof.

24. The method of claim 23, wherein said oxygen carrier is a hemoglobin-based oxygen carrier.

25. A preserved platelet package, comprising:

the preserved platelet composition of claim 20, stored in an oxygen-permeable or in an oxygen-impermeable bag.