Photochemical decontamination treatment of whole blood or blood components

• US 4,727,027 A
• Filed: 10/07/1985
• Issued: 02/23/1988
• Est. Priority Date: 05/02/1983
• Status: Expired due to Term

• Current Assignee: Miles, Inc. (Bayer AG)
• Original Assignee: Diamond Scientific Company (Bayer AG)
• Inventors: Wiesehahn, Gary P., Creagan, Richard P.
• Primary Examiner(s): Wiseman, Thomas G.
• Assistant Examiner(s): Tieskin, Robin Lyn
• Application Number:
  US06/785,356
• Time in Patent Office: 869 Days
• Field of Search: 435/173, 435/183, 435/188, 435/236, 435/238, 435/269, 435/800, 435/814, 435/172.1, 260/112 R, 260/112 B, 260/121, 424/89, 424/90, 424/101, 424/88, 424/92, 514/2, 514/6, 514/8, 530/350, 530/363, 530/380-394, 530/412-414, 530/427
• US Class Current: 435/173.2
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61M 1/3681 by irradiation
• CPC Class Codes: A61M 1/3683 using photoactive agents

Abstract

Biological compositions are decontaminated by treatment with furocoumarin derivatives and irradiation under particular conditions in which the proteins retain their original physiological activities and any pathogenic microorganisms and polynucleotide fragments thereof are rendered inactive. It has been found that reduction of the amount of dissolved oxygen in the treatment solution substantially inhibits denaturation of the proteins.

Claims

1. A method for decontaminating a blood clotting factor containing composition of viral contaminants, in a manner which substantially maintains the biological activity of the blood clotting factors, said method comprising adding to the blood clotting factor containing composition at least one furocoumarin, and irradiating the furocoumarin containing composition under U-V light, wherein the amount of furocoumarin and irradiation conditions are sufficient to inactivate substantially all the viral contaminants, and wherein the concentration of dissolved oxygen is reduced to a level sufficient to substantially inhibit the denaturation of the blood clotting factors.

2. A method as in claim 1, wherein the level of dissolved oxygen is reduced by addition of an oxygen scavenger to the composition.

3. A method as in claim 1, wherein the level of dissolved oxygen is reduced by equilibrium exchange with an inert or less reactive gas.

4. A method as in claim 1, wherein the level of dissolved oxygen and other reactive species is reduced by addition of a physiologically-acceptable protein.

5. A method as in claim 4, wherein the physiologically acceptable protein is human or bovine serum albumin.

6. A method as in claim 1, wherein the solubility of the furocoumarin in the aqueous composition is increased by the addition of from about 1% to 25% by weight of an organic solvent.

7. A method as in claim 6, wherein the organic solvent is selected from the group consisting of dimethyl sulfoxide, ethanol, glycerol, polyethylene glycol, and propylene glycol.

8. A method according to claim 1, wherein at least two furocoumarins are present.

9. A method according to claim 1 wherein any unreacted furocoumarin(s) or photobreakdown products thereof are selectively removed.

10. A method according to claim 1 wherein furocoumarins or biological components which have reacted with the furocoumarin(s) are selectively removed by antibodies to those modified components.

11. A method for decontaminating a blood clotting factor containing composition of viral contaminants in a manner which substantially maintains the biological activity of the blood clotting factors, said method comprising adding to the blood clotting factor containing composition at least one furocoumarin such that the total furocoumarin concentration is at least 1 μ

g/ml and not more than 300 μ

g/ml, and irradiating the furocoumarin containing composition under U-V light which wavelengths are in the range of about 300 nm to 400 nm and at an intensity of about 0.1 mw/cm² to 5 w/cm² and at a depth of at least 0.025 millimeters for a total irradiation time of about 5 minutes to about 12 hours, and wherein the level of dissolved oxygen in the blood clotting factor containing composition is substantially reduced to substantially inhibit the denaturation of the blood clotting factors.

12. A method as in claim 11, wherein the level of dissolved oxygen is reduced by addition of an oxygen scavenger to the composition.

13. A method as in claim 11, wherein the level of dissolved oxygen is reduced by equilibrium exchange with a less reactive gas.

14. A method as in claim 11, wherein the level of dissolved oxygen and other reactive species is reduced by addition of a physiologically-acceptable protein.

15. A method as in claim 14, wherein the physiologically acceptable protein is human or bovine serum albumin.

16. A method as in claim 11, wherein the solubility of the furocoumarin in the aqueous composition is increased by the addition of from about 1% to 25% by weight of an organic solvent.

17. A method as in claim 16, wherein the organic solvent is selected from the group consisting of dimethyl sulfoxide, ethanol, glycerol, polyethylene glycol, and propylene glycol.

18. A method according to claim 11, wherein two furocoumarins are added to said composition.

19. A method according to claim 18, wherein said two furocoumarins are 4'"'"'-hydroxymethyl-4,5'"'"',8-trimethylpsoralen and 4'"'"'-aminomethyl-4,5'"'"',8-trimethylpsoralen.

20. A method according to claim 11, wherein the viral contaminants comprise at least one of Hepatitis A, Hepatitis B, and Non-A Non-B Hepatitis viruses.

21. A method according to claim 11 wherein the viral contaminants comprise a virus which causes Acquired Immune Deficiency Syndrome (AIDS).

22. A method according to claim 11 wherein the furocoumarin added is 8-methoxypsoralen.