Methods of using an apparatus for prolonging survival of platelets using CMP-sialic acid, UDP-galactose or both
View Patent ↗The present invention provides modified platelets having a reduced platelet clearance and methods for reducing platelet clearance. Also provided are compositions for the preservation of platelets. The invention also provides methods for making a pharmaceutical composition containing the modified platelets and for administering the pharmaceutical composition to a mammal to mediate hemostasis.
1. A method for treating a platelet using an apparatus, wherein the apparatus comprises a first sterile container having one or more ports and containing a preparation of blood cells comprising platelets; and a second sterile container having one or more ports and containing two or more blood cell modifying agents; wherein the first sterile container is adapted to the second sterile container through a sterile conduit reversibly attached to a first container port and to a second container port, wherein the conduit further comprises a valve; wherein the steps of the method comprise:
processing the platelets using the apparatus such that the platelets are exposed to the two or more blood cell modifying agents that include UDP-galactose and cytidine 5′-monophospho-N-acetylneuraminic acid;
wherein the platelets are rendered cold-storage competent after being contacted with the two or more blood cell modifying agents.
2. The method of claim 1 , further comprising separating leukocytes from the blood cells prior to exposing the blood cells to the two or more blood cell modifying agents.
3. The method of claim 1 , wherein the blood cells are contacted with the two or more blood cell modifying agents before infusion of the treated blood cells into a patient.
4. The method of claim 1 , wherein the blood cells are contacted with the two or more blood cell modifying agents before cold storage of the blood cells.
5. The method of claim 1 , wherein the blood cells are contacted with the two or more blood cell modifying agents at the time of blood collection from a blood donor.
6. The method of claim 1 , further including separating the blood cells into subpopulations of platelets, plasma, red blood cells, and white blood cells.
7. The method of claim 1 , wherein the blood cells are contacted with the two or more blood cell modifying agents after the blood cells have been separated by apheresis.
8. A method for treating a platelet using an apparatus, wherein the apparatus comprises a first sterile container having one or more ports and containing a preparation of blood cells comprising platelets; and a second sterile container having one or more ports and containing two or more blood cell modifying agents; wherein the first sterile container is adapted to the second sterile container through a sterile conduit reversibly attached to a first container port and to a second container port; wherein the steps of the method comprise:
contacting the platelets with the two or more blood cell modifying agents, wherein the two or more blood cell modifying agents comprise UDP-galactose and cytidine 5′-monophospho-N-acetylneuraminic acid, to thereby obtain treated platelets.
9. The method of claim 8 , wherein an amount of each of the two or more blood cell modifying agents is between about 1 micromolar and about 10 millimolar.
10. The method of claim 8 , wherein an amount of each of the two or more blood cell modifying agents is between about 1 micromolar and about 1200 micromolar.
11. The method of claim 8 , further comprising storing the treated platelets for a period of time ranging between about 24 hours and about 20 days.
12. The method of claim 8 , further comprising storing the treated platelets for a period of time ranging between about 24 hours and about 7 days.
13. The method of claim 8 , further comprising storing the treated platelets for a period of time ranging between about 24 hours and about 5 days.
14. The method of claim 8 , further comprising storing the treated platelets at a temperature ranging between about 0° C. and about 4° C.
15. The method of claim 8 , further comprising storing the treated platelets at a temperature ranging between about 4° C. and about 15° C.
16. The method of claim 8 , further comprising storing the treated platelets at a temperature ranging between about 15° C. and about 37° C.
17. The method of claim 8 , wherein the platelets are contacted with the UDP-galactose and cytidine 5′-monophospho-N-acetylneuraminic acid simultaneously or sequentially.