Induction of and maintenance of nucleic acid damage in pathogens using riboflavin and light

• US 20040081956A1
• Filed: 08/25/2003
• Published: 04/29/2004
• Est. Priority Date: 06/02/2000
• Status: Active Grant

• Current Assignee: Terumo BCT Biotechnologies, LLC (Terumo Corporation)
• Original Assignee: Gambro, Inc. (DaVita Incorporated)
• Inventors: Keil, Shawn D., Lockerbie, Robert Owen, Kumar, Vijay, Goodrich, Raymond P.
• Granted Patent: US 7,901,673 B2
• Time in Patent Office: Days
• US Class Current: 435/2
• 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 2/084 Visible light
• CPC Class Codes: A61L 2/10 Ultraviolet radiation
• CPC Class Codes: A61L 2202/22 Blood or products thereof
• 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

Abstract

A process for damaging and maintaining damage to the nucleic acids of pathogens such as white blood cells, bacteria and viruses which may be contained in blood or blood components. This process comprises adding to the blood or blood component containing pathogens an effective amount of riboflavin, and exposing the fluid to light of an appropriate wavelength to damage the nucleic acid of the pathogen and to substantially maintain the damage to the pathogenic nucleic acids to allow for subsequent transfusion into a recipient.

Claims

1. A process for substantially maintaining damage to pathogen nucleic acid in a fluid containing pathogens and blood components comprising the steps of:

adding to the fluid a photosensitizer comprising riboflavin;

irradiating the fluid and photosensitizer with light at an appropriate wavelength to activate the photosensitizer to cause damage to the pathogen nucleic acid;

substantially maintaining the damage to the pathogen nucleic acid; and

wherein the damage to pathogen nucleic acid caused by the photosensitizer and light is substantially maintained during storage of the fluid after irradiation.

2. The process of claim 1 further comprising substantially maintaining the damage to the pathogen nucleic acid after transfusion into a recipient.

3. The process of claim 1 wherein the pathogen nucleic acid further comprises nucleic acid from undesirable cells and/or microorganisms.

4. The process of claim 1 further comprising adding a quencher to the fluid.

5. The process of claim 4 wherein the quencher further comprises a quencher selected from the group consisting essentially of glutathione, n-acetyl-cysteine, cysteine, adenine, histidine, tyrosine, tryptophan, ascorbate, vitimin E, trolox, TPGS and mixtures thereof.

6. The process of claim 1 further comprising adding to the fluid a solution containing additives to enhance blood component viability.

7. The process of claim 1 wherein the blood component further comprises platelets.

8. The process of claim 1 wherein the blood component further comprises red blood cells.

9. The process of claim 1 wherein the light used to irradiate the fluid and photosensitizer is in the UVB range.

10. The process of claim 1 wherein the riboflavin is added to the fluid at a final concentration of between about 50-500 μ

M.

11. A process for inactivating white blood cells which may be contained in a fluid comprising:

adding to the fluid containing white blood cells an effective amount of riboflavin;

exposing the fluid and riboflavin to light of an appropriate wavelength to activate the riboflavin and cause damage to the nucleic acid of the white blood cells; and

substantially maintaining the damage to the nucleic acids of the white blood cells to prevent re-activation of the white blood cells.

12. The process of claim 11 wherein the fluid further comprises red blood cells.

13. The process of claim 11 wherein the fluid further comprises platelets.

14. The process of claim 11 wherein the fluid further comprises plasma.

15. The process of claim 11 wherein the light to expose the fluid and riboflavin is in the UVB range.

16. The process of claim 11 wherein the riboflavin is added to the fluid at a final concentration of between about 50-500 μ

M.

17. A fluid suitable for transfusing into a patient comprising red blood cells treated by the process of claim 11.

18. A fluid suitable for transfusing into a patient comprising platelets treated by the process of claim 11.

19. A fluid suitable for transfusing into a patient comprising plasma treated by the process of claim 11.

20. A process for inactivating virus which may be contained in a blood product to be transfused into a patient comprising:

adding to the blood product containing virus an effective amount of riboflavin;

exposing the blood product and riboflavin to light of an appropriate wavelength to activate the riboflavin and cause damage to the nucleic acid of the virus; and

substantially maintaining the damage to the viral nucleic acids to allow for subsequent transfusion of the pathogen reduced blood product into a patient.

21. A process for providing pathogen reduced fluid containing blood or blood components suitable for re-infusion into a patient comprising:

damaging the nucleic acid of any pathogens which may be present with the blood or blood components;

adding riboflavin to the fluid containing blood or blood components and any pathogens; and

exposing the fluid to light to activate the riboflavin to maintain the nucleic acid damage of the pathogens.

22. The process of claim 21 wherein the step of exposing the fluid to light further comprises exposing the fluid to light in the UVB range.

23. The process of claim 21 wherein the riboflavin is added to the fluid at a final concentration of between about 50-500 μ

M.