Claims
- 1. A method for treating a fluid comprising a blood component to inactivate pathogens which may be present therein, comprising the steps of:
(a) adding an inactivation-effective, substantially non-toxic amount of a photosensitizer to said fluid; (b) adding nitric oxide to said fluid in an amount sufficient to increase dissolved nitric oxide content of said fluid and in an amount sufficient to improve a vital quality of said blood component; and (c) exposing said fluid to photoradiation of sufficient energy to activate said photosensitizer, for a sufficient time to substantially inactivate said pathogens.
- 2. The method of claim 1 wherein said increased dissolved nitric oxide content of said fluid is in an amount sufficient to also increase pathogen inactivation.
- 3. The method of claim 1 wherein the step of adding nitric oxide is performed by adding nitric oxide gas, adding one or more nitric oxide generators, or both.
- 4. The method of claim 1 wherein the step of adding nitric oxide is performed by adding nitric oxide gas, adding L-arginine, adding N-acetyl-cysteine, adding dibutyryl guanosine monophosphate, and/or adding dibutyryl adenosine monophosphate.
- 5. The method of claim 1 wherein the step of adding nitric oxide comprises adding nitric oxide gas.
- 6. The method of claim 1 wherein the step of adding nitric oxide comprises adding L-arginine.
- 7. The method of claim 6 comprising adding between about 100 micromolar and about 500 micromolar L-arginine.
- 8. The method of claim 6 comprising adding about 100 micromolar L-arginine.
- 9. The method of claim 1 wherein adding nitric oxide comprises adding N-acetyl-cysteine.
- 10. The method of claim 9 wherein said N-acetyl-cysteine is N-acetyl-L-cysteine.
- 11. The method of claim 9 comprising adding between about 100 micromolar and about 500 micromolar N-acetyl-cysteine.
- 12. The method of claim 9 comprising adding about 100 micromolar N-acetyl-cysteine.
- 13. The method of claim 1 further comprising the step of increasing the dissolved oxygen content of said fluid to an amount sufficient to enhance reaction of the photosensitizer in which singlet oxygen and reactive oxygen species (ROS) are formed.
- 14. The method of claim 1 further comprising the step of adding a quencher to said fluid.
- 15. The method of claim 1 further comprising the step of adding a glycolysis inhibitor to said fluid.
- 16. The method of claim 15 wherein said glycolysis inhibitor is 2-deoxy-D-glucose.
- 17. The method of claim 16 wherein said 2-deoxy-D-glucose is present at a concentration between about 1 millimolar and about 10 millimolar.
- 18. The method of claim 1 wherein said fluid comprises a blood component selected from the group consisting of plasma, platelets, red blood cells, white blood cells, and plasma proteins.
- 19. The method of claim 18 wherein said fluid comprises platelets.
- 20. The method of claim 19 wherein said fluid comprises platelets in a solution comprising plasma and storage solution.
- 21. The method of claim 1 performed in a blood product collection bag.
- 22. The method of claim 1 wherein said photosensitizer is selected from the group consisting of endogenous isoalloxazines and isoalloxazine derivative photosensitizers.
- 23. The method of claim 1 wherein said photosensitizer is riboflavin.
- 24. The method of claim 1 wherein the concentration of said photosensitizer in said fluid is about 50 micromolar.
- 25. The method of claim 5 comprising adding an amount of nitric oxide gas equivalent to between about 25 ml and about 1200 ml at about 1 atmosphere of pressure.
- 26. The method of claim 25 wherein the amount of nitric oxide gas is about 150 ml.
- 27. The method of claim 25 wherein the concentration of nitric oxide in said gas is between about 10 ppm and about 1000 ppm.
- 28. The method of claim 25 wherein the concentration of nitric oxide in said gas is between about 25 ppm and about 50 ppm.
- 29. The method of claim 5 wherein said nitric oxide gas is in a balance of about 20% oxygen and about 80% nitrogen.
- 30. The method of claim 1 wherein said vital quality of said blood component is selected from the group consisting of activation of said blood component, hypotonic shock response, lactate production, glucose consumption, pH, platelet swirl, and platelet aggregation.
- 31. The method of claim 1 wherein said pathogens are selected from the group consisting of extracellular and intracellular viruses, bacteria, bacteriophages, fungi, blood-transmitted parasites, and protozoa, and mixtures of any two or more of the foregoing.
- 32. The method of claim 31 wherein said viruses are selected from the group consisting of human immunodeficiency virus (HIV), hepatitis A, B and C viruses, sindbis virus, cytomegalovirus, vesicular stomatitis virus, herpes simplex viruses, e.g. types I and II, human T-lymphotropic retroviruses, HTLV-III, lymphadenopathy virus LAV/IDAV, parvovirus, transfusion-transmitted (TT) virus, and Epstein-Barr virus, bovine viral diarrhea virus, pseudorabies, West Nile virus, and mixtures of any two or more of the foregoing.
- 33. The method of claim 31 wherein said bacteriophages are selected from the group consisting of ΦX174, Φ6, λ, R17, T4, and T2, and mixtures of any two or more of the foregoing.
- 34. The method of claim 31 wherein said bacteria are selected from the group consisting of P. aeruginosa, S. aureus, S. epidermidis, E. coli, K. pneumoniae, E. faecalis, B. subtilis, S. pneumoniae, S. pyrogenes, S. viridans, B. cereus, E. aerogenes, propionabacter, C. perfringes, E. cloacae, P. mirabilis, S. cholerasuis, S. liquifaciens, S. mitis, Y. entercolitica, P. fluorescens, S. enteritidis, C. freundii, and S. marcescens, and mixtures of any two or more of the foregoing.
- 35. The method of claim 31 wherein said protozoa is P. falciparum.
- 36. A blood product decontaminated by the method of claim 1.
- 37. A biological composition comprising:
(a) a fluid; (b) an inactivation-effective, substantially non-toxic amount of an endogenous photosensitizer or endogenously-based derivative photosensitizer; and (c) dissolved nitric oxide in an amount greater than would be present in said fluid under an air atmosphere at ambient conditions without mixing.
- 38. The composition of claim 37 also comprising dissolved oxygen in an amount greater than would be present under an air atmosphere at ambient conditions without mixing.
- 39. The composition of claim 37 also comprising a quencher.
- 40. The composition of claim 37 also comprising a glycolysis inhibitor.
- 41. The composition of claim 37 wherein said fluid comprises one or more blood components selected from the group consisting of plasma, red blood cells, white blood cells, platelets and plasma proteins.
- 42. The composition of claim 37 wherein said fluid comprises platelets.
- 43. The composition of claim 37 wherein said fluid comprises platelets and storage solution.
- 44. The composition of claim 37 also comprising pathogens.
- 45. The composition of claim 44 wherein said pathogens are selected from the group consisting of extracellular and intracellular viruses, bacteria, bacteriophages, fungi, blood-transmitted parasites, and protozoa, and mixtures of any two or more of the foregoing.
- 46. The composition of claim 44 in which said pathogens have been substantially inactivated.
- 47. A translucent or transparent blood component bag wherein the contents of said blood component bag comprise the composition of claim 37.
- 48. The blood component bag of claim 47 wherein the contents of which also comprise air.
- 49. The blood component bag of claim 47 wherein the contents of which also comprise more oxygen than is present in air.
- 50. The blood component bag of claim 47 wherein the contents of which also comprise more nitric oxide than is present in air.
- 51. The blood component bag of claim 47 wherein the contents of which also comprise more oxygen and more nitric oxide than is present in air.
- 52. A decontamination system for a fluid comprising:
(a) a leak-proof transparent or translucent container for the fluid; (b) a photosensitizer source for providing photosensitizer to said container, said photosensitizer source being connectible to an inlet of said container; (c) a nitric oxide source connectible to an inlet of said container for providing nitric oxide to said container; and (d) a photoirradiator for irradiating said container.
- 53. The decontamination system of claim 52 also comprising an oxygen source connectible to an inlet of said container for providing oxygen to said container.
- 54. The decontamination system of claim 52 also comprising a quencher source for providing quencher to said container, said quencher source being connectible to an inlet of said container.
- 55. The decontamination system of claim 52 also comprising a glycolysis inhibitor source for providing glycolysis inhibitor to said container, said glycolysis inhibitor source being connectible to an inlet of said container.
- 56. The decontamination system of claim 52 also comprising an agitator for agitating said container.
- 57. The decontamination system of claim 52 wherein said container is a blood product or blood collection bag.
- 58. The decontamination system of claim 57 wherein said blood product bag or blood collection bag contains said fluid wherein said fluid comprises a blood component selected from the group consisting of plasma, platelets, red blood cells, white blood cells, and plasma proteins.
- 59. The decontamination system of claim 57 wherein said nitric oxide source contains a composition selected from the group consisting of nitric oxide gas, L-arginine, and N-acetyl-cysteine.
- 60. The decontamination system of claim 52 wherein said blood component is platelets.
- 61. A method for making a decontamination system comprising the steps of:
(a) providing a set of components comprising:
(i) a leak-proof transparent or translucent container for a fluid wherein said container comprises one or more inlets; (ii) a photosensitizer source for providing photosensitizer to said container, said photosensitizer source comprising an outlet connectible to one of said inlets of said container; (iii) a nitric oxide source for providing nitric oxide to said container, said nitric oxide source comprising an outlet connectible to one of said inlets of said container; and (iv) a photoirradiator for irradiating said container; (b) connecting the outlet of said photosensitizer source to an inlet of said container; (c) connecting the outlet of said nitric oxide source to an inlet of said container; and (d) positioning said photoirradiator in radiating proximity to said container.
- 62. The method of claim 61 wherein said set of components also comprises an oxygen source having an outlet for providing oxygen to said container, said oxygen source being connectible to an inlet of said container, and said method comprises connecting the outlet of said oxygen source to an inlet of said container.
- 63. A method of increasing the storage life of platelets, said method comprising the steps of:
(a) placing said platelets in solution in a container larger than the volume of the solution; (b) adding nitric oxide to said solution to increase dissolved nitric oxide content of said solution in an amount sufficient to improve storage life of said platelets; (c) adding a photoactivator to said solution and irradiating said solution to activate said photoactivator; and (d) storing said platelets for a period greater than five days without destroying the usefulness of said platelets.
- 64. The method of claim 63 also comprising dissolving an amount of oxygen in said solution greater than that would be dissolved in said solution under an air atmosphere at ambient conditions without agitation.
- 65. The method of claim 63 further comprising removing substantially all gas phase from said container after step (c).
- 66. The method of step of claim 65 further comprising adding nitric oxide to said solution after step (c) to increase dissolved nitric oxide content of said solution in an amount sufficient to further increase storage life of said blood component.
- 67. The method step of claim 63 further comprising adding a glycolysis inhibitor to said solution in an amount sufficient to further increase storage life of said blood component.
- 68. The method of claim 63 further comprising adding a quencher to said solution.
- 69. A method for treating platelets to inactivate pathogens which may be present therein, comprising the steps of:
(a) adding 7,8-dimethyl-10-ribityl isoalloxazine to a fluid comprising said platelets in storage solution at a ratio of about 27:73 platelets (in plasma):storage solution, whereby the 7,8-dimethyl-10-ribityl isoalloxazine concentration of said fluid is between about 1 and about 200 micromolar; (b) adding nitric oxide gas to the atmosphere in contact with said fluid to increase dissolved nitric oxide content of said fluid in an amount sufficient to increase a vital quality of said platelets, wherein the concentration of said nitric oxide gas is between about 10 ppm and about 500 ppm; and (c) exposing said fluid to photoradiation at an energy between about 5 and about 12 J/cm2 to activate the photosensitizer, for at least about five to about twenty minutes, to substantially inactivate said pathogens.
- 70. The method of claim 69 further comprising increasing the dissolved oxygen content of said fluid to about five times the oxygen content said fluid would have under an air atmosphere, by mixing air into said fluid, or by exposing said fluid to an atmosphere of substantially pure oxygen, before step (c).
- 71. The method of claim 69 further comprising adding quencher to said fluid.
- 72. The method of claim 69 further comprising adding glycolysis inhibitor to said fluid.
- 73. The method of claim 69 further comprising adding L-arginine to said fluid.
- 74. The method of claim 69 further comprising adding N-acetyl-cysteine to said fluid.
- 75. A method for treating platelets to inactivate pathogens which may be present therein, comprising the steps of:
(a) adding 7,8-dimethyl-10-ribityl isoalloxazine to a fluid comprising said platelets in storage solution at a ratio of about 27:73 platelets (in plasma):storage solution, whereby the 7,8-dimethyl-10-ribityl isoalloxazine concentration of said fluid is between about 1 and about 200 micromolar; (b) adding L-arginine to said fluid in an amount sufficient to increase a vital quality of said platelets, wherein the concentration of said L-arginine is between about 25 micromolar and about 500 micromolar; and (c) exposing said fluid to photoradiation at an energy between about 5 and about 12 J/cm2 to activate the photosensitizer, for at least about five to about twenty minutes, to substantially inactivate said pathogens.
- 76. The method of claim 75 further comprising the step of increasing the dissolved oxygen content of said fluid to about five times the oxygen content the fluid would have under an air atmosphere, by mixing air into said fluid, or by exposing said fluid to an atmosphere of substantially pure oxygen, before step (c).
- 77. The method of claim 75 further comprising the step of adding quencher to said fluid.
- 78. The method of claim 75 further comprising the step of adding glycolysis inhibitor to said fluid.
- 79. The method of claim 75 further comprising the step of adding nitric oxide gas to said fluid.
- 80. The method of claim 75 further comprising the step of adding N-acetyl-cysteine to said fluid.
- 81. A method for treating platelets to inactivate pathogens which may be present therein, comprising the steps of:
(a) adding 7,8-dimethyl-10-ribityl isoalloxazine to a fluid comprising said platelets in storage solution at a ratio of about 27:73 platelets (in plasma):storage solution, whereby the 7,8-dimethyl-10-ribityl isoalloxazine concentration of said fluid is between about 1 and about 200 micromolar; (b) adding N-acetyl-cysteine to said fluid in an amount sufficient to increase a vital quality of said platelets, wherein the concentration of said N-acetyl-cysteine is between about 25 micromolar and about 500 micromolar; and (c) exposing said fluid to photoradiation at an energy between about 5 and about 12 J/cm2 to activate the photosensitizer, for at least about five to about twenty minutes, to substantially inactivate said pathogens.
- 82. The method of claim 81 further comprising the step of increasing the dissolved oxygen content of said fluid to about five times the oxygen content the fluid would have under an air atmosphere, by mixing air into said fluid, or by exposing said fluid to an atmosphere of substantially pure oxygen, before step (c).
- 83. The method of claim 81 further comprising the step of adding quencher to said fluid.
- 84. The method of claim 81 further comprising the step of adding glycolysis inhibitor to said fluid.
- 85. The method of claim 81 further comprising the step of adding L-arginine to said fluid.
- 86. The method of claim 81 further comprising the step of adding nitric oxide gas to said fluid.
- 87. The method of claim 1 wherein the step of adding nitric oxide comprises adding a nitric oxide donor.
- 88. The method of claim 1 wherein the step of adding nitric oxide comprises adding a composition selected from the group consisting of: DEA-NO, DETA-NO, DETA-NONOate, PAPA-NO, sodium nitroprusside, and nitroglycerine.
- 89. The method of claim 1 wherein the step of adding nitric oxide is performed before, after, or both before and after the step of exposing said fluid to photoradiation.
- 90. The method of claim 14 wherein the step of adding a quencher is performed before, after, or both before and after the step of exposing said fluid to photoradiation.
- 91. The method of claim 15 wherein the step of adding a glycolysis inhibitor is performed before, after, or both before and after the step of exposing said fluid to photoradiation.
- 92. A blood product decontaminated by the method of claim 1 wherein said blood product is suitable for administration for a patient for at least about five days.
- 93. A blood product decontaminated by the method of claim 1 wherein said blood product is suitable for administration for a patient for more than five days.
- 94. The bag of claim 47 wherein said bag comprises a nitric oxide generator.
- 95. The bag of claim 47 wherein said bag comprises a coating wherein said coating comprises a nitric oxide generator.
- 96. A method of increasing the storage life of a blood component, said method comprising the steps of:
(a) placing said blood component in solution in a container larger than the volume of the solution; (b) adding nitric oxide to said solution to increase dissolved nitric oxide content of said solution in an amount sufficient to improve storage life of said blood component; (c) adding a photoactivator to said solution and irradiating said solution to activate said photoactivator; and (d) storing said blood component for a period greater than five days without destroying the usefulness of said blood component.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 60/355,393, filed Feb. 8, 2002 and to U.S. Provisional Application No. 60/373,936 filed Apr. 19, 2002. This application is also a continuation-in-part of U.S. patent application Ser. No. 10/328,717, filed Dec. 23, 2002, which claims priority to U.S. Provisional Application No. 60/344,109, filed Dec. 28, 2001. This application is also a continuation-in-part of U.S. patent application Ser. No. 10/159,781, filed May 30, 2002, which claims priority to U.S. Provisional Application No. 60/294,866, filed May 30, 2001. This application is a continuation-in-part of U.S. patent application entitled “Inactivation of West Nile Virus and Malaria Using Photosensitizers,” attorney docket number 3-03, filed Feb. 3, 2003, which claims priority to U.S. Provisional Application No. 60/353,162, filed Feb. 1, 2002, and also to U.S. application Ser. No. 09/586,147, filed Jun. 2, 2000 which is a continuation-in-part of U.S. application Ser. No. 09/357,188 filed Jul. 20, 1999 which is a continuation-in-part of U.S. application Ser. No. 09/119,666 filed Jul. 21, 1998. This application is a continuation-in-part of U.S. patent application entitled “Addition of Glycolysis Inhibitor to a Pathogen Reduction and Storage Solution,” attorney docket number B-0112, filed Feb. 3, 2003, that claims priority to U.S. Provisional Application 60/353,319, filed Feb. 1, 2002. This application is a continuation-in-part of U.S. patent application Ser. No. 09/777,727, filed Feb. 5, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09/420,652, filed Oct. 19, 1999. All of these applications are hereby incorporated by reference to the extent not inconsistent with the disclosure herewith.
Provisional Applications (4)
|
Number |
Date |
Country |
|
60355393 |
Feb 2002 |
US |
|
60373936 |
Apr 2002 |
US |
|
60344109 |
Dec 2001 |
US |
|
60294866 |
May 2001 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
10328717 |
Dec 2002 |
US |
Child |
10364661 |
Feb 2003 |
US |
Parent |
10159781 |
May 2002 |
US |
Child |
10364661 |
Feb 2003 |
US |