Nitric oxide in a pathogen inactivation process
First Claim
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.
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Abstract
This invention provides methods and compositions for using nitric oxide in a photoradiation pathogen inactivation process for whole blood and blood components to improve pathogen kill and to improve preservation of the quality of the blood components. This invention provides methods for using nitric oxide in combination with oxygen, photosensitizers, quencher and/or glycolysis inhibitor, and compositions comprising blood components decontaminated by these methods. Nitric oxide is provided using nitric oxide gas, or nitric oxide generators such as L-arginine, and/or N-acetyl-cysteine. This invention also provides compositions suitable for photoradiation pathogen inactivation that include fluid comprising a blood component, a photosensitizer, and dissolved nitric oxide. This invention provides decontamination systems useful for performing the methods of this invention and methods for making the decontamination systems. This invention also provides methods for decontaminating fluids and methods for increasing the storage life and quality of photochemically decontaminated platelets.
86 Citations
96 Claims
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1. A method for treating a fluid comprising a blood component to inactivate pathogens which may be present therein, comprising the steps of:
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(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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 87, 88, 89, 90, 91, 92, 93)
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37. A biological composition comprising:
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(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. - View Dependent Claims (38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 94, 95)
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52. A decontamination system for a fluid comprising:
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(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. - View Dependent Claims (53, 54, 55, 56, 57, 58, 59, 60)
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61. A method for making a decontamination system comprising the steps of:
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(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. - View Dependent Claims (62)
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63. A method of increasing the storage life of platelets, said method comprising the steps of:
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(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. - View Dependent Claims (64, 65, 66, 67, 68)
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69. A method for treating platelets to inactivate pathogens which may be present therein, comprising the steps of:
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(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. - View Dependent Claims (70, 71, 72, 73, 74)
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75. A method for treating platelets to inactivate pathogens which may be present therein, comprising the steps of:
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(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. - View Dependent Claims (76, 77, 78, 79, 80)
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81. A method for treating platelets to inactivate pathogens which may be present therein, comprising the steps of:
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(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. - View Dependent Claims (82, 83, 84, 85, 86)
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96. A method of increasing the storage life of a blood component, said method comprising the steps of:
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(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.
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Specification