Inactivation of West Nile virus and malaria using photosensitizers

• US 20040018997A1
• Filed: 02/03/2003
• Published: 01/29/2004
• Est. Priority Date: 07/21/1998
• Status: Active Grant

• Current Assignee: Terumo BCT Biotechnologies, LLC (Terumo Corporation)
• Original Assignee: Gambro, Inc. (DaVita Incorporated)
• Inventors: Goodrich, Raymond P., Reddy, Heather
• Granted Patent: US 7,049,110 B2
• Time in Patent Office: Days
• US Class Current: 514/43
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 41/17 by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61L 2/0082 using chemical substances
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: A61L 2/08 Radiation
• CPC Class Codes: A61L 2/10 Ultraviolet radiation
• CPC Class Codes: A61M 1/0213 with isolated sections of the tube used as additive reservoirs
• CPC Class Codes: A61M 1/3681 by irradiation
• CPC Class Codes: A61M 1/3683 using photoactive agents
• CPC Class Codes: A61M 1/3693 using separation based on different densities of components, e.g. centrifuging
• CPC Class Codes: A61M 2205/123 with incorporated reservoirs
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods and apparatuses are provided for inactivation of microorganisms in fluids or on surfaces. Preferably the fluids contain blood or blood products and comprise biologically active proteins. Preferred methods include the steps of adding an effective, non-toxic amount of a photosensitizer to a fluid and exposing the fluid to photoradiation sufficient to activate the photosensitizer whereby microorganisms are inactivated.

Claims

1. A method for treating a fluid to inactivate at least one type of parasite or virus that may be present therein, said fluid containing one or more components selected from the group consisting of:

biologically active protein, blood, and blood constituents, without destroying the biological activity of such component, comprising;

(a) adding an inactivation effective, substantially non-toxic amount of an endogenous photosensitizer or endogenously-based derivative photosensitizer other than a porphyrin to the fluid; and

(b) exposing the fluid of step (a) to photoradiation sufficient to activate the photosensitizer, whereby at least one parasite or virus in the fluid is inactivated.

2. The method of claim 1, wherein the parasite comprises P. falciparum.

3. The method of claim 1, wherein the fluid comprises red blood cells and the photoradiation has a wavelength of about 447 nm.

4. The method of claim 1, further comprising adding air to the fluid and photosensitizer before exposing the fluid to photoradiation.

5. The method of claim 1, wherein the photosensitizer is a nucleic-acid-targeted non-toxic, photoactivatable compound which does not produce toxic photolytic breakdown products.

6. The method of claim 1, wherein the photosensitizer is endogenous.

7. The method of claim 6, wherein the photosensitizer is 7,8-dimethyl-10-ribityl isoalloxazine.

8. The method of claim 1, wherein the virus comprises West Nile virus.

9. The method of claim 1, wherein the photoradiation comprises one or more wavelengths in the visible spectrum.

10. The method of claim 1, wherein the photoradiation comprises one or more wavelengths in the ultraviolet spectrum.

11. The method of claim 1, wherein said fluid of step (a) is exposed to a source of photoradiation at a depth selected to ensure penetration of the photoradiation through the fluid and inactivation of the parasite or virus.

12. The method of claim 1, wherein the fluid comprises blood constituents.

13. The method of claim 1, wherein the fluid is whole blood.

14. The method of claim 1, wherein the fluid is a separated blood product.

15. The method of claim 1, wherein an endogenous photosensitizer is added to anticoagulant and said anticoagulant is added to the fluid.

16. The method of claim 1, wherein the photosensitizer is capable of inactivating viruses or parasites at a pH of about 7.4.

17. The method of claim 1, wherein the photosensitizer is capable of inactivating viruses or parasites in the presence of plasma, cells or blood components.

18. The method of claim 1, wherein the photosensitizer inactivates at least one type of parasite or virus present in human blood.

19. A fluid comprising biologically active protein, blood or blood constituents and inactivated virus or parasite and photosensitizer or photoproduct thereof, made by the method of claim 1.

20. The fluid of claim 19, wherein the fluid is a component of a kit.

21. A kit for testing biologically active protein, blood or blood constituents for the presence of a microorganism, wherein one sample of biologically active protein, blood or blood constituent is inactivated using the method of claim 1, and a second biologically active protein, blood or blood constituent is tested for the presence of a microorganism.

22. The kit of claim 21, wherein the microorganism is the West Nile Virus.

23. A blood product comprising inactivated virus or parasite and photosensitizer or photoproduct thereof, made by the method of claim 1.

24. A system for treating a fluid to inactivate at least one virus or parasite which may be present therein comprising:

(a) means for adding an effective, non-toxic amount of an endogenous or endogenously-based photosensitizer other than a porphyrin 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; and

(c) a photoradiation source for providing sufficient photoradiation to the fluid in said container of a type and amount selected to activate the photosensitizer.

25. The system of claim 24, wherein said photoradiation source provides light in the visible spectrum.

26. The system of claim 24, wherein said photoradiation source provides light in the ultraviolet spectrum.

27. The system of claim 24, further comprising a photoradiation enhancer.

28. The system of claim 27, wherein the photoradiation enhancer comprises a reflective surface.

29. The system of claim 24, comprising a light guide for conducting photoradiation from said photoradiation source to said photopermeable container.

30. The system of claim 24, further comprising means for flowing the fluid into and out of the container.

31. The system of claim 24, further comprising a temperature monitor.

32. An apparatus for separating whole blood into blood components comprising the system of claim 24.