Patent EA-002655-B1 (EA)
Title: Method and apparatus for inactivation of biological contaminants uising photosensitizers
Inventor: GOODRICH RAYMOND PAUL JR
IPC: A61L2/10
Filed: 1999-07-21
Abstract: 1. A method for treating a fluid to inactivate microorganisms which may be present therein, said fluid containing one or more components selected from the group consisting of protein, blood, and blood constituents, said method comprising: (a) adding an inactivation-effective, substantially non-toxic amount of an endogenous photosensitizer or endogenously-based derivative photosensitizer to said fluid; (b) exposing the fluid of step (a) to photoradiation sufficient to activate the photosensitizer, whereby said microorganisms are inactivated. 2. The method of claim 1 wherein said photosensitizer is a photo-activatable compound, whose photolytic products (if any) are of low or no toxicity to humans or animals. 3. The method of claim 1 wherein said photosensitizer is an endogenous photosensitizer selected from the group consisting of 7,8-dimethyl-10-ribityl isoalloxazine, 7,8-dimethylalloxazine, 7,8,10-trimethylisoalloxazine, alloxazine mononucleotide, isoalioxazine-adenosine dinucleotide. 4. The method of claim 1 wherein said photosensitizer is 7,8-dimethyl-10-ribityl isoalloxazine. 5. The method of claim 1 wherein said microorganisms are selected from the group consisting of bacteria, bacteriophages, and intracellular and extracellular viruses. 6. The method of claim 1 wherein said microorganisms are bacteria. 7. The method of claim 1 wherein said microorganisms are selected from the group consisting of HIV viruses, hepatitis viruses, sindbis virus, cytomegalovirus, vesicular stomatitis virus, herpes simplex viruses, vaccinia virus, human T-lymphotropic retroviruses, HTLV-III, lymphadenopahy virus LAV/IDAV, parvovirus, transfusion-transmitted (TT) virus, Epstein-Barr virus, bacteriophages .PHI.X174, .PHI.6, .lambda., R17, T4, T2, P. aeruginosa, S. aureus, S. epidermidis, L. monocytogenes, E. coli, K. pneumoniae and S. marcescens. 8. The method of claim 1 wherein said photoradiation is light in the visible spectrum. 9. The method of claim 1 wherein said photoradiation is light in the ultraviolet spectrum. 10. The method of claim 1 wherein said photoradiation comprises light in both the visible and ultraviolet spectrum. 11. The method of claim 1 wherein about half of said photoradiation is in the ultraviolet spectrum and about half is in the visible spectrum. 12. The method of claim 1 wherein said exposing step further comprises flowing the fluid containing said photosensitizer past a source of photoradiation at a rate and depth selected to ensure penetration of the photoradiation through the fluid and inactivation of the microorganisms. 13. The method of claim 1 further comprising containing said fluid and photosensitizer in a container transparent to said photoradiation and exposing said fluid to said photoradiation. 14. The method of claim 13 comprising agitating said container during photoradiation. 15. The method of claim 1 comprising placing said fluid in a container transparent to said photoradiation, adding said photosensitizer to said fluid in powder form, agitating said container and exposing said container to said photoradiation. 16. The method of claim 1 wherein said fluid comprises blood constituents. 17. The method of claim 1 wherein said fluid comprises whole blood. 18. The method of claim 1 wherein said fluid comprises a separated blood product. 19. The method of claim 1 wherein said fluid comprises platelets separated from whole blood. 20. The method of claim 1 wherein said fluid comprises red blood cells separated from whole blood. 21. The method of claim 1 wherein said fluid comprises serum separated from whole blood. 22. The method of claim 1 wherein said fluid comprises plasma separated from whole blood. 23. The method of claim 1 wherein said fluid comprises a therapeutic protein composition. 24. The method of claim 1 wherein said fluid contains a biologically-active protein selected from the group consisting of factor VIII, Von Willebrand factor, factor IX, factor X, factor XI, Hageman factor, prothrombin, anti-thrombin III, fibronectin, plasminogen, plasma protein fraction, peritoneal dialysis solutions, immune serum globulin, modified immune globulin, albumin, plasma growth hormone, somatomedin, plasminogen streptokinase complex, ceruloplasmin, transferrin, haptoglobin, antitrypsin and prekallikrein. 25. The method of claim 1 wherein said photosensitizer is added to anticoagulant and said anticoagulant is added to said fluid. 26. A method of claim 1 wherein an enhancer is added to said fluid prior to exposing said fluid to photoradiation. 27. A method of claim 27 wherein said enhancer is selected from the group consisting of adenine, histidine, cysteine, tyrosine, tryptophan, ascorbate, N-acetyl-L-cysteine, propyl gallate, glutathione, mercaptopropionylglycine, dithiothreotol, nicotinamide, BHT, BHA, lysine, serine, methionine, glucose, mannitol, trolox, glycerol, and mixtures thereof. 28. A method for treating a fluid to inactivate microorganisms which may be present therein, said method comprising: (a) adding an inactivation-effective substantially non-toxic amount of an endogenous photosensitizer or endogenously-based derivative photosensitizer to said fluid; (b) exposing the fluid of step (a) to photoradiation sufficient to activate the photosensitizer, whereby said microorganisms are inactivated. 29. The method of claim 28 wherein said fluid is a food product. 30. The method of claim 28 wherein said fluid is a drink meant for human or animal consumption. 31. The method of claim 28 wherein said fluid is a peritoneal solution. 32. A fluid comprising biologically active protein, blood or blood constituent and an endogenous photosensitizer or endogenously-based derivative photosensitizer, made by the method of claim 1. 33. A blood product derivative comprising an endogenous photosensitizer or endogenously-based derivative photosensitizer, made by the method of claim 1. 34. A fluid comprising biologically active protein, blood or blood constituents, an endogenous photosensitizer or endogenously-based derivative photosensitizer and an enhancer. 35. A system for treating a fluid to inactivate microorganisms which may be present therein comprising: (a) a container comprising said fluid and an endogenous photosensitizer or endogenously-based derivative photosensitizer, said container being equipped with input means, and having a photopermeable surface sufficient to allow exposure of the fluid therein to an amount of photoradiation sufficient to activate the photosensitizer; (b) at least one photoradiation source for providing sufficient photoradiation to the fluid in said container of a type and amount selected to activate the photosensitizer whereby microorganisms present are inactivated. 36. The system of claim 35 wherein said photoradiation source provides light in the visible spectrum. 37. The system of claim 35 wherein said photoradiation source provides light in the ultraviolet spectrum. 38. The system of claim 35 wherein said at least one photoradiation source provides light in both the visible and ultraviolet spectrum. 39. The system of claim 35 also comprising a photoradiation enhancer. 40. The system of claim 39 wherein said photoradiation enhancer comprises a reflective surface. 41. The system of claim 35 comprising a light guide for conducting photoradiation from said photoradiation source to said photopermeable container. 42. The system of claim 35 also comprising a temperature monitor. 43. The system of claim 35 also comprising means for flowing said fluid into and out of said container. 44. The system of claim 35 also comprising means for agitating said fluid in said container. 45. A system for inactivation of microorganisms in a fluid containing such microorganisms comprising: (a) means for adding an effective amount of an endogenous photosensitizer or endogenously-based derivative photosensitizer to said fluid; (b) a photopermeable container for said fluid in fluid communication with said means for adding photosensitizer having a depth and length selected to allow exposure of the fluid of step (a) therein to an amount of photoradiation sufficient to activate the photosensitizer at a selected flow rate; (c) means for producing said selected flow rate of said fluid through said container; and (d) at least one photoradiation source for providing sufficient photoradiation to the fluid in said container of a type and amount selected to activate the photosensitizer. 46. A system for treating a fluid to inactivate microorganisms which may be present therein comprising: (a) a photosensitizer in powdered form; (b) a photopermeable container for containing said fluid and photosensitizer; (c) means for agitating said container; (d) at least one photoradiation source for providing sufficient photoradiation to the fluid in said container of a type and amount selected to activate the photosensitizer whereby microorganisms are inactivated. 47. The system of claim 46 wherein said photopermeable container is a transparent plastic bag. 48. The system of claim 46 wherein said means for agitating said container comprise a shaker table. 49. The system of claim 46 wherein said photopermeable container contains said photosensitizer prior to addition of said fluid. 50. A method of inactivating microorganisms on a surface comprising: (a) applying to said surface an inactivation-effective amount of an endogenous photosensitizer or endogenously-based derivative photosensitizer; and b) exposing said surface to photoradiation sufficient to activate the photosensitizer. 51. The method of claim 50 wherein said surface is a food surface. 52. The method of claim 50 wherein said surface is the surface of an animal carcass. 53. The method of claim 50 wherein said surface is a food-preparation surface. 54. The method of claim 50 wherein said surface is a surface of a bathing or washing vessel. 55. The method of claim 50 wherein said surface is a surface of an animal skin. 56. The method of claim 50 wherein said