Plasma-free medium for platelet storage

Abstract

Blood platelet concentrate in a plasma-free medium. Method for storage of blood platelets in a plasma-free medium which comprises centrifuging plasma to obtain a platelet pellet, removing the supernatant plasma, and resuspending the platelet pellet in a balanced salt medium. The balanced salt medium in an isotonic solution and may be selected from well known physiologically tolerable salt mediums. Additives to enhance platelet storage can be added to the salt medium.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
       1. A method for the preparation of .[.a.]. .Iadd.an essentially plasma-free .Iaddend.blood platelet concentrate for administration to animals which comprises centrifuging plasma to obtain a platelet pellet,   removing the supernatant plasma, and   resuspending the platelet pellet in a medium consisting essentially of: a balanced, physiological compatible, saline solution; an anticoagulant; and one or more additives to enhance stability of the platelets selected from (a) nutrients to improve the storage life of the platelets, (b) reversible inhibitors for platelet activation, (c) substances to raise cyclic adenosine monophosphate levels which have reversible effects on platelets, and (d) buffering agents which are physiologically compatible.   
     
     
       2. A method as claimed in claim 1 wherein the nutrients are selected from fructose, adenine or acetyl CoA. 
     
     
       3. A method as claimed in claim 1 wherein the reversible inhibitors for platelet activation are selected from indomethacin, quinacrine or vitamin E. 
     
     
       4. A method as claimed in claim 1 wherein the substances to raise cyclic adenosine monophosphate levels are selected from prostaglandins E 1 , D 2  or I 2 . 
     
     
       5. A method as claimed in claim 1 wherein the buffering agents are selected from phosphate or amino acids. 
     
     
       6. A method as claimed in claim 5 wherein the amino acids are selected from histidine, cysteine, tyrosine, lysine or arginine. 
     
     
       7. A method as claimed in claim 1 wherein the balanced salt medium is selected from Spinner salt solution, Tyrode's solution, Seligmann's balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solutions or Puck's saline. 
     
     
       8. A method as claimed in claim 1 wherein the balanced salt medium is a Tyrode's solution. 
     
     
       9. A method as claimed in claim 6 wherein the Tyrode's solution contains a phosphate buffer or a histidine buffer. 
     
     
       10. A method as claimed in claim 6 wherein extraction and a washing step is used to remove plasma from platelets prior to final suspension in the Tyrode's solution. 
     
     
       11. A method as claimed in claim 7 wherein extraction is used to remove plasma from platelets prior to final suspension in the modified Tyrode's solution. 
     
     
       12. A method as claimed in claim 1 wherein the plasma is human plasma. 
     
     
       13. A method as claimed in claim 1 wherein the plasma is derived from freshly collected whole blood or by apheresis. 
     
     
       14. A method as claimed in claim 1 wherein the plasma is derived from freshly collected whole human blood or by apheresis on a human donor. 
     
     
       15. A method as claimed in claim 1 wherein the plasma is human plasma. 
     
     
       16. A method as claimed in claim 1 wherein the plasma is derived from freshly collected whole blood or by apheresis. 
     
     
       17. A method as claimed in claim 1 wherein the plasma is derived from freshly collected whole human blood or by apheresis on a human donor. 
     
     
       18. .[.A.]. .Iadd.An essentially plasma-free .Iaddend.platelet concentrate composition for administration to animals comprising blood platelets suspended in a medium consisting essentially of: a balanced, physiologically compatible, saline solution;   an anticoagulant; and   one or more additives to enhance stability of the platelets selected from (a) nutrients to improve the storage life of the platelets, (b) reversible inhibitors for platelet activation, (c) substances to raise cyclic adenosine monophosphate levels which have reversible effects on platelets, and (d) buffering agents which are physiologically compatible.   
     
     
       19. A platelet concentrate as claimed in claim 18 wherein the nutrients are selected from fructose, adenine or acetyl CoA. 
     
     
       20. A platelet concentrate as claimed in claim 18 wherein the reversible inhibitors for platelet activation are selected from indomethacin, quinacrine or vitamin E. 
     
     
       21. A platelet concentrate as claimed in claim 18 wherein the substances to raise cyclic adenosine monophosphate levels are selected from prostaglandins E 1 , D 2  or I 2 . 
     
     
       22. A platelet concentrate as claimed in claim 18 wherein the buffering agents are selected from phosphate or amino acids. 
     
     
       23. A platelet concentrate as claimed in claim 22, wherein the amino acids are selected from histidine, cysteine, tyrosine, lysine or arginine. 
     
     
       24. A platelet concentrate as claimed in claim 18, wherein the balanced salt medium is selected from Spinner salt solution, Tyrode's solution, Seligmann's balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solutions or Puck's saline. 
     
     
       25. A platelet concentrate as claimed in claim 18 wherein the balanced salt medium is a Tyrode's solution. 
     
     
       26. A platelet concentrate as claimed in claim 25 wherein the Tyrode's solution contains a phosphate buffer or a histidine buffer. 
     
     
       27. A platelet concentrate as claimed in claim 18 wherein the plasma is human plasma. 
     
     
       28. A platelet concentrate as claimed in claim 18 wherein the human plasma is derived from freshly collected whole blood or by apheresis on a human donor. .Iadd. 
     
     
       29.  An essentially plasma-free storage-stable package of blood platelets, which comprises a concentrate of blood platelets suspended in a volume of physiologically acceptable salt solution, said suspension being sealedly enclosed within a blood storage member. .Iaddend. .Iadd.30. The storage-stable package as defined by claim 29 which is devoid of a buffering agent. .Iaddend. .Iadd.31. The storage-stable package as defined by claim 29 which is devoid of an anticoagulant. .Iaddend. .Iadd.32. The storage-stable package as defined by claim 29, said blood storage member comprising a blood collection and storage bag. .Iaddend. .Iadd.33. The storage-stable package as defined by claim 32, said blood collection and storage bag being highly permeable. .Iaddend. .Iadd.34. The storage-stable package as defined by claim 29, said blood storage member comprising a plastic blood collection and storage bag. .Iaddend. .Iadd.35. The storage-stable package as defined by claim 29, which further comprises a buffering agent. .Iaddend. .Iadd.36. The storage-stable package as defined by claim 29, wherein the physiologically compatible salt solution is selected from the group consisting of Spinner salt solution, Tyrode's solution, Seligmann balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solution or Puck's saline. .Iaddend. 
     
     
        .Iadd. 7.  The storage-stable package as defined by claim 36, wherein the physiologically compatible salt solution is Tyrode's solution. .Iaddend. .Iadd.38. The storage-stable package as defined by claim 37, wherein Tyrode's solution contains a phosphate buffer or a histidine buffer. .Iaddend. .Iadd.39. The storage-stable package as defined by claim 29, wherein the blood platelets are human blood platelets. .Iaddend. .Iadd.40. The storage-stable package as defined by claim 39, wherein the blood platelets are derived from platelet-rich plasma from whole blood or by apheresis on a human donor. .Iaddend. .Iadd.41. The storage-stable package as defined by claim 29, further comprising an anticoagulant. .Iaddend. .Iadd.42. The storage-stable package as defined by claim 29, further comprising saline-citrate-buffer. .Iaddend. .Iadd.43. The storage-stable package as defined by claim 29, further comprising 
     
     
        saline-citrate-buffer-nutrient. .Iaddend. .Iadd.44.  A composition of matter comprising an essentially plasma-free storage-stable concentrate of blood platelets suspended in a volume of physiologically acceptable salt solution, said composition exhibiting no worse than normal platelet aggregation. .Iaddend. .Iadd.45. The composition of matter as defined by claim 44, further comprising an additive adopted to enhance platelet function under conditions of storage, or to prolong the storage life thereof. .Iaddend. .Iadd.46. The composition of matter as defined by claim 45, which said additive is a buffering agent. .Iaddend. .Iadd.47. The composition of matter as defined by claim 44, wherein the physiologically compatible salt solution is selected from the group consisting of Spinner salt solution, Tyrode's solution, Seligmann balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solution or Puck's saline. .Iaddend. .Iadd.48. The composition of matter as defined by claim 47, wherein the physiologically compatible salt solution is Tyrode's 
     
     
        solution. .Iaddend. .Iadd.49.  The composition of matter as defined by claim 48, wherein Tyrode's solution contains a phosphate buffer or a histidine buffer. .Iaddend. .Iadd.50. The composition of matter as defined by claim 44, wherein the blood platelets are human blood platelets. .Iaddend. .Iadd.51. The composition of matter as defined by claim 50, wherein the blood platelets are derived from platelet-rich plasma from whole blood or by apheresis on a human donor. .Iaddend. .Iadd.52. The composition of matter as defined by claim 44, further comprising an anticoagulant. .Iaddend. .Iadd.53. The composition of matter as defined by claim 44, further comprising saline-citrate-buffer. .Iaddend. .Iadd.54. The composition of matter as defined by claim 44, further comprising saline-citrate-buffer-nutrient. .Iaddend. .Iadd.55. A method for the storage of essentially plasma-free blood platelets, which comprises confining a concentrate of said blood platelets suspended in a volume of physiologically acceptable salt solution within a blood storage member, 
     
     
        for a period of time of at least 72 hours. .Iaddend. .Iadd.56.  The method as defined by claim 55, comprising confining the suspension within said blood storage member under conditions of agitation. .Iaddend. .Iadd.57. The method as defined by claim 55, wherein a buffering agent is contained in the storage member. .Iaddend. .Iadd.58. The method as defined by claim 55, wherein the physiologically compatible salt solution is selected from the group consisting of Spinner salt solution, Tyrode's solution, Seligmann balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solution or Puck's saline. .Iaddend. .Iadd.59. The method as defined by claim 58, wherein the physiologically compatible salt solution is Tyrode's solution. .Iaddend. .Iadd.60. The method as defined by claim 59, wherein Tyrode's solution contains a phosphate buffer or a histidine buffer. .Iaddend. .Iadd.61. The method as defined by claim 55, 
     
     
        wherein the plasma is human plasma. .Iaddend. .Iadd.62.  The method as defined by claim 61, wherein the plasma is derived from human whole blood or by apheresis on a human donor. .Iaddend. .Iadd.63. The method as defined by claim 55, wherein the storage member is highly permeable. .Iaddend. .Iadd.64. The method as defined by claim 55, wherein an anticoagulant is contained in the storage member. .Iaddend. .Iadd.65. The method as defined by claim 55, wherein saline-citrate-buffer is present within the storage member. .Iaddend. .Iadd.66. The method as defined by claim 55, wherein saline-citrate-buffer-nutrient is present within the storage member. .Iaddend. .Iadd.67. A method for the treatment of thrombocytopenia in a patient in need of such treatment, which comprises infusing into such patient an effective amount of an essentially plasma-free concentrate of blood platelets suspended in a volume of 
     
     
        physiologically compatible salt solution. .Iaddend. .Iadd.68.  The method as defined by claim 67, wherein the physiologically compatible salt solution is selected from the group consisting of Spinner salt solution, Tyrode's solution, Seligmann balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solution or Puck's saline. .Iaddend. .Iadd.69. The method as defined by claim 68, wherein the physiologically compatible salt solution is Tyrode's solution. .Iaddend. .Iadd.70. The method as defined by claim 69, wherein Tyrode's solution contains a phosphate buffer or histidine buffer. .Iaddend.