Photodynamic viral deactivation with sapphyrins

• US 5,041,078 A
• Filed: 12/21/1989
• Issued: 08/20/1991
• Est. Priority Date: 03/06/1989
• Status: Expired due to Term

• Current Assignee: Baylor Research Foundation A Nonprofit Corporation of The State of Texas, Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Baylor Research Foundation A Nonprofit Corporation of The State of Texas, Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Sogandares-Bernal, Frank, Sessler, Jonathan L., Judy, Millard M., Harriman, Anthony, Matthews, J. Lester, Newman, Joseph T., Maiya, Bhaskar G.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Rose, Sharon
• Application Number:
  US07/454,300
• Time in Patent Office: 607 Days
• Field of Search: 604/4-6, 604/20, 604/403, 604/408, 604/416, 540/145
• US Class Current: 604/6.08
• CPC Class Codes: A61K 41/0038 Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy radiotherapy per se A61N5/10
• CPC Class Codes: A61K 41/0076 PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• CPC Class Codes: A61K 47/546 Porphyrines; Porphyrine with an expanded ring system, e.g. texaphyrine
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings

Abstract

The present invention demonstrates a method of photodynamic inactivation of viruses having a membranous envelope, such as Herpes simplex type 1 and Human immunodeficiency type 1 viruses. The method uses substituted sapphyrin compounds to effect viral deactivation during radiation with light at or near the absorption wavelength of the sapphyrin compound. A highly reactive species selectively toxic to infectious agents is produced.

One particular sapphyrin compound useful for the practice of the invention is 8,17-bis(carboxymethyl)-3,12,13,22-tetraethyl-2,7,18,23-tetramethylsapphyrin (Sapphyrin 2). The most preferred sapphyrin sapphyrin compound for the practice of the invention is 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin (Sapphyrin 1).

The method is particularly suitable for inactivation of viruses in blood and blood products.

Claims

1. A method of photodynamic inactivation of infectious agents, comprising:

forming a mixture by adding a decaalkylsapphyrin or a dicarboxy functionalized decaalkylsapphyrin compound to a fluid comprising infectious agents; and

subjecting said mixture to irradiation with light at a wavelength at or near the absorption maximum of said decaalkylsapphyrin or dicarboxy functionalized decaalkylsapphyrin compound for a time and at an intensity sufficient to inactivate said infectious agents.

2. The method of claim 1 wherein the decaalkylsapphyrin compound is 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin.

3. The method of claim 1 wherein the dicarboxy functionalized decaalkylsapphyrin compound is a dicarboxy-functionalized analog of 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin.

4. The method of claim 1 wherein the dicarboxy functionalized decaalkylsapphyrin compound is 8,17-bis(carboxymethyl)-3,12,13,22-tetraethyl-2,7,18,23-tetramethylsapphyrin.

5. The method of claim 1 wherein the wavelength is between about 600 nm and 700 nm.

6. The method of claim 1 wherein the wavelength is about 680 nm.

7. The method of claim 1 wherein the light is provided by a laser.

8. The method of claim 1 wherein the irradiation is at an intensity of from about 20 mW/cm² to about 50 mW/cm².

9. The method of claim 1 wherein the irradiation results in an exposure of the mixture to 10 Joules/cm².

10. The method of claim 1 wherein the the decaalkylsapphyrin or dicarboxy functionalized decaalkylsapphyrin compound in the mixture is at a concentration between about 4 uM and 35 uM.

11. A method of photodynamic inactivation of viruses or retroviruses, comprising:

obtaining a viral or retroviral suspension in a fluid;

adding a decaalkylsapphyrin or a dicarboxy functionalized decaalkylsapphyrin compound to said suspension; and

irradiating said suspension with light at a wavelength at or near the visible absorption maximum of said decaalkylsapphyrin or dicarboxy functionalized decaalkylsapphyrin compound for a time and at an intensity sufficient to effect inactivation of virus or retrovirus in said suspension.

12. The method of claim 11 wherein the wavelength is 680 nm.

13. The method of claim 11 wherein the intensity sufficient to effect the inactivation is about 20 mW/cm² to about 40 mW/cm².

14. The method of claim 11 wherein the irradiating sufficient to effect the inactivation is in an amount of about 10 J/cm².

15. The method of claim 11 wherein the viral or retroviral suspension comprises cytomegalovirus, hepatitis virus type B;

non-A, non-B hepatitis virus, human lymphotrophic virus type 1, human immunodeficiency virus type 1, simian immunodeficiency virus, or herpes simplex virus type 1.

16. The method of claim 11 wherein the viral or retroviral suspension comprises a membranous enveloped virus.

17. The method of claim 11 wherein the decaalkylsapphyrin compound is 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin.

18. The method of claim 11 wherein the dicarboxy functionalized decaalkylsapphyrin compound is 8,17-bis(carboxymethyl)-3,12,13,22-tetraethyl-2,7,18,23-tetramethylsapphyrin.

19. The method of claim 11 wherein the fluid is blood or a blood product.

20. A method of photodynamic inactivation of enveloped viruses or retroviruses in blood, comprising:

circulating virus-containing or retrovirus-containing blood through a transparent tube arranged in multiple planar loops;

adding a decaalkylsapphyrin or a dicarboxy functionalized decaalkylsapphyrin compound to said circulating blood; and

irradiating said circulating blood at a wavelength of about 680 nm.

21. The method of claim 20 wherein the decaalkylsapphyrin compound is 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin.

22. The method of claim 20 wherein the dicarboxy functionalized decaalkylsapphyrin compound is 8,17-bis(carboxymethyl)-3,12,13,22-tetraethyl-2,7,18,23-tetramethylsapphyrin.

23. A method of photodynamic deactivation of infectious agents in a fluid, comprising:

mixing a decaalkylsapphyrin or a dicarboxy functionalized decaalkylsapphyrin compound with a fluid to be purified;

irradiating said fluid at a wavelength at or near the absorption maximum of said decaalkylsapphyrin or dicarboxy functionalized decaalkylsapphyrin

compound at an intensity and for a period of time sufficient to inactivate one or more infectious agents that may be present in said fluid.

24. The method of claim 23 wherein said fluid is irradiated at a wavelength of about 680 nm.

25. The method of claim 23 wherein the irradiating is at an energy of about 10 J/cm².

26. The method of claim 23 wherein the decaalkylsapphyrin or dicarboxy functionalized decaalkylsapphyrin compound in the fluid is at a concentration of about 4 uM to about 35 uM.

27. The method of claim 23 wherein the dicarboxy functionalized decaalkylsapphyrin compound is 8,17-bis(carboxymethyl)-3,12,13,22-tetraethyl-2,7,18,23-tetramethylsapphyrin.

28. The method of claim 23 wherein the fluid is further characterized as being blood.

29. The method of claim 23 wherein the fluid is further characterized as being a blood product.

30. The method of claim 23 wherein the infectious agent is a virus or retrovirus.

31. The method of claim 30 wherein the virus or retrovirus is further characterized as having an envelope.

32. The method of claim 30 wherein the virus or retrovirus is characterized as being cytomegalovirus, hepatitis virus type B;

non-A, non-B hepatitis virus, human lymphotrophic virus type 1, human immunodeficiency virus type 1, simian immunodeficiency virus, Epstein barr virus, or herpes simplex virus type 1.

33. The method of claim 23 wherein the infectious agent is Tympanosoma cruzi or malaria plasmodium.