Claims
- 1. A method removing a positively charged microbicidal compound and/or degradation products or derivatives thereof from a composition, comprising
contacting a composition with a cation exchange resin, under conditions and for a time sufficient to allow a positively charged microbicidal compound and/or degradation products or derivatives thereof in the composition to bind to the cation exchange resin, and separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition.
- 2. The method of claim 1, wherein the positively charged microbicidal compound is positively charged at physiological pH.
- 3. The method of claim 1, wherein the cation exchange resin is not contained within a matrix.
- 4. The method of claim 1, wherein the positively charged microbicidal compound is an aziridino compound.
- 5. The method of claim 4, wherein the aziridino compound is an ethyleneimine oligomer.
- 6. The method of claim 1, wherein the composition is a blood product.
- 7. The method of claims 6, wherein the method does not substantially change the biological properties of the treated blood product relative to untreated blood product.
- 8. The method of claim 7, wherein the biological properties of the treated blood product are not substantially changed after storage at 4° C. relative to untreated blood product.
- 9. The method of claim 6, wherein the blood product is a composition comprising red blood cells.
- 10. The method of claim 9, wherein the method results in a level of hemolysis of the red blood cells that is no greater than cell washing
- 11. The method of claim 9, wherein the surface of the cation exchange resin particles does not induce substantial hemolysis of the red blood cells.
- 12. The method of claim 6, further comprising washing the blood product after removal of the positively charged microbicidal compound bound to the cation exchange resin.
- 13. The method of claim 6, further comprising washing the blood product prior to contacting the composition with a cation exchange resin.
- 14. The method of claim 1, wherein the cation exchange resin is a strongly acidic cation exchange resin.
- 15. The method of claim 1, wherein the cation exchange resin comprises sulfonic groups.
- 16. The method of claim 1, wherein the diameter of the cation exchange resin particles is at least about 100 microns.
- 17. The method of claim 16, wherein the size of the particles is between about 150 microns and about 300 microns.
- 18. The method of claim 1, wherein the cation exchange resin particles are substantially non-breakable under moderate mechanical stress in dry conditions or suspensions.
- 19. The method of claim 1, wherein the cation exchange resin particles are compatible with water miscible solvents.
- 20. The method of claim 19, wherein the cation exchange resin particles do not dissolve or degrade when contacted with water miscible solvents.
- 21. The method of claim 1, wherein the cation exchange resin particles do not create fine particles under moderate mechanical stress.
- 22. The method of claim 1, wherein the cation exchange resin particles have a cation exchange capacity of at least about 1 meq/ml.
- 23. The method of claim 22, wherein the cation exchange resin particles have a cation exchange capacity of at least about 2 meq/ml.
- 24. The method of claim 22, wherein the cation exchange resin particles have a cation exchange capacity of at least about 3 meq/ml.
- 25. The method of claim 24, wherein the cation exchange resin particles have a cation exchange capacity of at least about 5 meq/ml.
- 26. The method of claim 1, wherein the method is performed under pH conditions of from about pH 4 to about pH 14.
- 27. The method of claim 26, wherein the method is performed under pH conditions of from about pH 6 to about pH 8.
- 28. The method of claim 27, wherein the method is performed at about pH 7.
- 29. The method of claim 1, wherein the cation exchange resin particles do not leach toxic components into water based media or blood products.
- 30. The method of claim 1, wherein the cation exchange resin particles are sterilized by gamma or thermal sterilization.
- 31. The method of claim 1, wherein the cation exchange resin is DOWEX™ 50W×8.
- 32. The method of claim 1, wherein the method is performed using a column format, in which the step of contacting a composition with a cation exchange resin is performed by flowing the composition into a column packed with the cation exchange resin, and the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by flowing the composition out of the column.
- 33. The method of claim 32, wherein the column is run by gravity or by moderate pressure with a flow rate of less than about 50 ml/min.
- 34. The method of claim 33, wherein the flow rate is less than about 10 ml/min.
- 35. The method of claim 32, wherein the flow rate is less than about 1 ml/min.
- 36. The method of claim 1, wherein the cation exchange resin particles have substantially no pores.
- 37. The method of claim 1, wherein the amount of positively charged microbicidal compound in the composition is reduced by at least about 2 logs.
- 38. The method of claim 37, wherein the amount of positively charged microbicidal compound in the composition is reduced by at least about 3 logs.
- 39. The method of claim 38, wherein the amount of positively charged microbicidal compound in the composition is reduced by at least about 4 logs.
- 40. The method of claim 39, wherein the amount of positively charged microbicidal compound in the composition is reduced by at least about 5 logs.
- 41. The method of claim 1, wherein the method is performed at a temperature of at least about 20° C.
- 42. The method of claim 1, wherein the method is performed at a temperature of at least about 25° C.
- 43. The method of claim 1, wherein the method is performed at a temperature of at least about 27° C.
- 44. The method of claim 1, wherein the method is performed at a temperature of at least about 30° C.
- 45. The method of claim 32, wherein the dimensions of the column expressed as a ratio of diameter:length are about 1:5 or less.
- 46. The method of claim 45, wherein the dimensions of the column expressed as a ratio of diameter:length are about 1:10 or less.
- 47. The method of claim 45, wherein the dimensions of the column expressed as a ratio of diameter:length are about 1:20 or less.
- 48. The method of claim 1, wherein method is performed in a column format, the flow rate is from about 1 ml/min to about 2 ml/min, the temperature is about 25° C., and the dimensions of the column expressed as a ratio of diameter:length are about 1:10 or less.
- 49. The method of claim 1, wherein method is performed in a batch format.
- 50. The method of claim 49, wherein the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by filtration of the composition to remove the cation exhange resin.
- 51. The method of claim 49, wherein the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by centrifugation of the composition to remove the cation exchange resin.
- 52. The method of claim 49, wherein the step of contacting the composition with the cation exchange resin is performed by adding the cation exchange resin in a permeable container to the composition.
- 53. The method of claim 52, wherein the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by removing the permeable container from the composition.
- 54. The method of claim 49, wherein the step of contacting the composition with the cation exchange resin is performed by adding the composition to a container that contains cation exchange resin.
- 55. The method of claim 54, wherein the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by removing the composition from the container.
- 56. The method of claim 54, wherein the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by removing the resin and bound positively charged microbicidal compound and/or degradation products or derivatives thereof from the container.
- 57. The method of claim 49, wherein the step of contacting the composition with the cation exchange resin is performed by adding the cation exchange resin to the composition.
- 58. The method of claim 57, wherein the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by filtration of the composition to remove the cation exhange resin.
- 59. The method of claim 57, wherein the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by centrifugation of the composition to remove the cation exchange resin.
- 60. The method of claim 49-59, wherein the steps of contacting the composition with the cation exchange resin and separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition are performed at least twice.
- 61. The method of any of claims 49-60, wherein the composition comprises cells, further comprising washing the cells.
- 62. The method of claim 61, wherein the cells are washed using an automated cell washer.
- 63. The method of any of claims 1-62, wherein the concentration of microbicidal compound is reduced by at least about 50%.
- 64. The method of claim 63, wherein the concentration of microbicidal compound is reduced by at least about 1 log.
- 65. The method of claim 64, wherein the concentration of microbicidal compound is reduced by at least about 2 logs.
- 66. The method of claim 65, wherein the concentration of microbicidal compound is reduced by at least about 3 logs.
- 67. The method of claim 66, wherein the concentration of microbicidal compound is reduced by at least about 4 logs.
- 68. A method for removal of an intracellular positively charged microbicidal compound and/or degradation products or derivatives thereof from a cell treated with a positively charged microbicidal compound, comprising
contacting a composition containing a cell treated with a positively charged microbicidal compound with a cation exchange resin, under conditions and for a time sufficient to allow the positively charged microbicidal compound and/or degradation products or derivatives thereof to bind to the cation exchange resin.
- 69. The method of claim 68, further comprising a step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the cell.
- 70. The method of claim 68, wherein the positively charged microbicidal compound is positively charged at physiological pH.
- 71. The method of claim 68, wherein the cation exchange resin is not contained within a matrix.
- 72. The method of claim 68, wherein the positively charged microbicidal compound is an aziridino compound.
- 73. The method of claim 72, wherein the aziridino compound is an ethyleneimine oligomer.
- 74. The method of claim 68, wherein the composition is a blood product.
- 75. The method of claims 74, wherein the method does not substantially change the biological properties of the treated blood product relative to untreated blood product.
- 76. The method of claim 75, wherein the biological properties of the treated blood product are not substantially changed after storage at 4° C. relative to untreated blood product.
- 77. The method of claim 74, wherein the blood product is a composition comprising red blood cells.
- 78. The method of claim 77, wherein the method results in a level of hemolysis of the red blood cells that is no greater than cell washing
- 79. The method of claim 77, wherein the surface of the cation exchange resin particles does not induce substantial hemolysis of the red blood cells.
- 80. The method of claim 74, further comprising washing the blood product after removal of the positively charged microbicidal compound bound to the cation exchange resin.
- 81. The method of claim 74, further comprising washing the blood product prior to contacting the composition with a cation exchange resin.
- 82. The method of claim 68, wherein the cation exchange resin is a strongly acidic cation exchange resin.
- 83. The method of claim 68, wherein the cation exchange resin comprises sulfonic groups.
- 84. The method of claim 68, wherein the diameter of the cation exchange resin particles is at least about 100 microns.
- 85. The method of claim 84, wherein the size of the particles is between about 150 microns and about 300 microns.
- 86. The method of claim 68, wherein the cation exchange resin particles are substantially non-breakable under moderate mechanical stress in dry conditions or suspensions.
- 87. The method of claim 68, wherein the cation exchange resin particles are compatible with water miscible solvents.
- 88. The method of claim 87, wherein the cation exchange resin particles do not dissolve or degrade when contacted with water miscible solvents.
- 89. The method of claim 68, wherein the cation exchange resin particles do not create fine particles under moderate mechanical stress.
- 90. The method of claim 68, wherein the cation exchange resin particles have a cation exchange capacity of at least about 1 meq/ml.
- 91. The method of claim 90, wherein the cation exchange resin particles have a cation exchange capacity of at least about 2 meq/ml.
- 92. The method of claim 90, wherein the cation exchange resin particles have a cation exchange capacity of at least about 3 meq/ml.
- 93. The method of claim 92, wherein the cation exchange resin particles have a cation exchange capacity of at least about 5 meq/ml.
- 94. The method of claim 68, wherein the method is performed under pH conditions of from about pH 4 to about pH 14.
- 95. The method of claim 94, wherein the method is performed under pH conditions of from about pH 6 to about pH 8.
- 96. The method of claim 95, wherein the method is performed at about pH 7.
- 97. The method of claim 68, wherein the cation exchange resin particles do not leach toxic components into water based media or blood products.
- 98. The method of claim 68, wherein the cation exchange resin particles are sterilized by gamma or thermal sterilization.
- 99. The method of claim 68, wherein the cation exchange resin is DOWEX™ 50W×8.
- 100. The method of claim 68, wherein the method is performed using a column format, in which the step of contacting a composition with a cation exchange resin is performed by flowing the composition into a column packed with the cation exchange resin, and the step of separating the positively charged microbicidal compound and/or degradation products or derivatives thereof bound to the cation exchange resin from the composition is performed by flowing the composition out of the column.
- 101. The method of claim 100, wherein the column is run by gravity or by moderate pressure with a flow rate of less than about 50 ml/min.
- 102. The method of claim 101, wherein the flow rate is less than about 10 ml/min.
- 103. The method of claim 100, wherein the flow rate is less than about 1 ml/min.
- 104. The method of claim 68, wherein the cation exchange resin particles have substantially no pores.
- 105. The method of claim 68, wherein the amount of positively charged microbicidal compound in the composition is reduced by at least about 2 logs.
- 106. The method of claim 105, wherein the amount of positively charged microbicidal compound in the composition is reduced by at least about 3 logs.
- 107. The method of claim 106, wherein the amount of positively charged microbicidal compound in the composition is reduced by at least about 4 logs.
- 108. The method of claim 107, wherein the amount of positively charged microbicidal compound in the composition is reduced by at least about 5 logs.
- 109. The method of claim 68, wherein the method is performed at a temperature of at least about 20° C.
- 110. The method of claim 68, wherein the method is performed at a temperature of at least about 25° C.
- 111. The method of claim 68, wherein the method is performed at a temperature of at least about 27° C.
- 112. The method of claim 68, wherein the method is performed at a temperature of at least about 30° C.
- 113. The method of claim 100, wherein the dimensions of the column expressed as a ratio of diameter:length are about 1:5 or less.
- 114. The method of claim 113, wherein the dimensions of the column expressed as a ratio of diameter:length are about 1:10 or less.
- 115. The method of claim 113, wherein the dimensions of the column expressed as a ratio of diameter:length are about 1:20 or less.
- 116. The method of claim 68, wherein method is performed in a column format, the flow rate is from about 1 ml/min to about 2 ml/min, the temperature is about 25° C., and the dimensions of the column expressed as a ratio of diameter:length are about 1:10 or less.
- 117. A blood product treated according to the method of any of claims 1-116.
- 118. A container for blood product comprising cation exchange resin.
- 119. The container of claim 118, wherein the cation exchange resin is loose.
- 120. The container of claim 118, wherein the cation exchange resin is contained within a permeable enclosure.
- 121. The container of claim 118, wherein the cation exchange resin is a strong cation exchanger.
- 122. The container of claim 118, wherein the amount of cation exchange resin is sufficient to reduce the amount of a positively charged microbicidal compound and/or degradation products or derivatives thereof in the blood product after contact with the resin.
- 123. The container of claim 122, wherein the amount of cation exchange resin is sufficient to reduce the amount of the positively charged microbicidal compound and/or degradation products or derivatives thereof by at least about 50%.
- 124. The container of claim 122 or 123, wherein the positively charged microbicidal compound is an ethyleneimine oligomer.
RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. § 119(e) from U.S. provisional patent application serial No. 60/440,287, filed Jan. 15, 2003, the entire disclosure of which is incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60440287 |
Jan 2003 |
US |