Photodynamic cellular and acellular organism eradication utilizing a photosensitive material and benzalkonium chloride

• US 8,187,278 B2
• Filed: 12/21/2001
• Issued: 05/29/2012
• Est. Priority Date: 08/25/1998
• Status: Active Grant

• Current Assignee: Advanced Photodynamic Technologies, Inc. (Ondine Biomedical, Inc.)
• Original Assignee: Advanced Photodynamic Technologies, Inc. (Ondine Biomedical, Inc.)
• Inventors: Biel, Merrill A.
• Primary Examiner(s): SHAY, DAVID M
• Application Number:
  US10/026,198
• Publication Number:
  US 20020091424A1
• Time in Patent Office: 3,812 Days
• Field of Search: 607/88, 607/89
• US Class Current: 606/88
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• 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 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• 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 41/17 by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61N 5/0624 for eliminating microbes, germs, bacteria on or in the body

Abstract

The invention relates to a method of photoeradication of cellular and acellular organisms including the steps of providing a surface acting agent containing benzalkonium chloride in association with a cellular or acellular organism, the surface acting agent disorienting a membrane structure so that said membrane no longer functions as an effective osmotic barrier; providing a photosensitive material in association with the cellular or acellular organism; and applying light in association with the cellular or acellular organism to cause a disruption of the organism. The method according to the present invention may be utilized in invitro and invivo treatment protocols for infections, sterilization procedures, cancer cell eradication, virus and fungus eradication, spore eradication, and biofilm organism eradication. Additional aspects of the invention include particular combinations of photosensitive materials and surfactants for use in photodynamic therapies.

Claims

1. A method of photodynamic disruption of cellular organisms comprising:

applying a surface acting agent containing benzalkonium chloride at a concentration of between 0.001% to 1.0% to a cell membrane of a cellular organism, said surface acting agent disorienting a cell membrane so that said cell membrane no longer functions as an effective osmotic barrier;

passing a photosensitive material through the disoriented membrane and into the cell interior; and

applying light to the cellular organism to cause a cellular disruption of the cellular organism.

2. The method of cellular organism disruption of claim 1 wherein the surface acting agent and the photosensitive material are provided in a combined solution.

3. The method of cellular organism disruption of claim 2 wherein the combined solution is provided in proximity to the cellular organism via a topical application.

4. The method of cellular organism disruption of claim 1 wherein the step of applying the surface acting agent and the step of passing the photosensitive material is performed on cellular organisms located on a surface of a medical prosthesis.

5. The method of cellular organism disruption of claim 1 wherein the photosensitive material is monomeric, dimeric, or polymeric.

6. The method of cellular organism disruption of claim 1 wherein the cellular organism is associated with an air filtration/decontamination process.

7. The method of cellular organism disruption of claim 1 wherein the cellular organism is a microbe, a spore, a fungus, or a cancer cell.

8. The method of cellular organism disruption of claim 1 wherein the surface acting agent contains benzalkonium chloride provided in a concentration range of between 0.005% to 0.05%.

9. The method of cellular organism disruption of claim 1 wherein the step of applying the surface acting agent precedes the step of passing the photosensitive material by between 1 to 30 minutes.

10. The method of cellular organism disruption of claim 1 wherein the step of applying light to the cellular organism occurs for a period of between 5 seconds to 1 hour and results in cellular organism death.

11. The method of cellular organism disruption of claim 1 wherein the step of applying a light includes a light wavelength ranging from 450 nm to 780 nm and a light dosage ranging from 10 J/cm² to 100 J/cm² and a light dosage rate ranging from 50 mw/cm² to 250 mw/cm².

12. The method of cellular organism disruption of claim 1 wherein the step of applying the surface acting agent includes providing more than one of a plurality of different surface acting agents.

13. The method of cellular organism disruption of claim 12 wherein the step of passing the photosensitive material includes providing more than one of a plurality of different photosensitive materials.

14. A method of photodynamic disruption of organisms comprising:

topically applying a surface acting agent containing benzalkonium chloride at a concentration of between 0.001% to 1.0% to a cell site with an organism, said surface acting agent disorienting a membrane of the organism so that said membrane no longer functions as an effective osmotic barrier;

passing a photosensitive material in association with the organism, said photosensitive material being accumulated within the membrane of the organism; and

applying light to the organism to cause a disruption of the organism.

15. The method of organism disruption of claim 14 wherein the surface acting agent and the photosensitive material are in a combined solution.

16. The method of organism disruption of claim 14 wherein the step of applying the surface acting agent and the step of passing the photosensitive material-occurs on a surface of a medical prosthesis.

17. The method of organism disruption of claim 14 wherein the organism is associated with an air filtration/decontamination device.

18. The method of organism disruption of claim 14 wherein the photosensitizing agent is monomeric, dimeric, or polymeric.

19. The method of organism disruption of claim 14 wherein the benzalkonium chloride is provided in a concentration range of between 0.005% to 0.5%.

20. The method of organism disruption of claim 14 wherein the step of applying light results in organism destruction.

21. The method of organism disruption of claim 14 wherein the step of applying light occurs for a period of between 5 seconds to 1 hour and results in organism death.

22. The method of organism disruption of claim 21 wherein the step of applying light occurs for a period of between 2 to 20 minutes.

23. The method of acellular disruption of claim 14 wherein the step of applying the surface acting agent precedes the step of providing the photosensitive material by between 1 to 30 minutes.

24. The method of organism disruption of claim 14 wherein the step of applying the surface acting agent includes applying more than one of a plurality of different surface acting agents.

25. The method of organism disruption of claim 14 wherein the step of passing the photosensitive material includes passing more than one of a plurality of different photosensitive materials.

26. The method of organism disruption of claim 14 wherein the step of applying a light includes a light wavelength ranging from 450 nm to 780 nm and a light dosage ranging from 10 J/cm² to 100 J/cm² and a light dosage rate ranging from 50 mw/cm² to 250 mw/cm².

27. The method of organism disruption of claim 14 wherein the organism is from a group containing:

a virus, a spore, and a plasmid.

28. A method of photodynamic disruption of cells comprising the steps of:

identifying an area of cell activity;

applying a concentration including a combination of a benzalkonium chloride compound at a concentration of between 0.001% to 1.0% and a photosensitive material to the area of cell activity, said benzalkonium chloride compound disorienting a cell membrane so that said membrane no longer functions as an effective osmotic barrier, and so that said photosensitive material is able to pass through the disoriented cell membrane; and

exposing the area of cell activity to light having a light wavelength, a light dosage and a light dosage rate to cause photodynamic cellular disruption.

29. The method of photodynamic disruption of cells of claim 28 wherein the step of identifying an area of cell activity includes an examination and identification of a cell site on a living body, and the step of applying the concentration includes an application of the concentration to the cell site of the living body.

30. The method of photodynamic disruption of cells of claim 28 wherein the step of identifying an area of cell activity includes identifying a medical prosthesis or device for sterilization procedure, and the step of providing the concentration includes an application of the concentration to a cell site of the prosthesis.

31. The method of photodynamic disruption of cells of claim 28 wherein the step of identifying an area of cell activity includes identifying an air filtration/decontamination device, and the step of providing the concentration includes an application of the concentration to a cell site within the device.

32. A method of photodynamic eradication of organisms within a biofilm of a medical prosthesis, said method comprising the steps of:

applying a photosensitive material and a surfactant to a surface of the prosthesis supporting a biofilm;

allowing the surfactant to disrupt membranes of the organisms within the biofilm;

waiting a period of time until the photosensitive material accumulates within the organisms;

providing a source of light illumination having predetermined light characteristics; and

illuminating the organisms within the biofilm layer with the light source to achieve a photodynamic eradication of organisms within the biofilm layer.

33. The method of claim 32 wherein the surfactant is benzalkonium chloride provided in at a concentration of between 0.001% to 1.0%.

34. The method of claim 33 wherein the step of applying the photosensitive material and the surfactant is via an impregnation of compounds upon a surface of the prosthesis.

35. The method of claim 33 wherein the step of illuminating the biofilm layer is achieved by an internal illumination of the prosthesis.

36. The method of claim 33 wherein the step of illuminating the biofilm layer is achieved by an external light source illuminating the biofilm layer.

37. A method of photodynamic eradication of organisms within a biofilm layer of an endotracheal tube, said method comprising the steps of

providing a photosensitive material and a surfactant to a surface of the endotracheal tube supporting a biofilm layer;

accumulating photosensitive material within the organisms comprising the biofilm;

allowing the surfactant to disrupt membranes of the organisms within the biofilm;

waiting a period of time until the photosensitive material accumulates within organisms;

providing a source of light illumination having predetermined light characteristics; and

illuminating the biofilm layer of the endotracheal tube with the light source to achieve a photodynamic eradication of organisms within the biofilm layer.

38. The method of claim 37 wherein the surfactant is benzalkonium chloride provided at a concentration of between 0.001% to 1.0%.

39. The method of claim 37 wherein the step of providing the photosensitive material and the surfactant is via an impregnation of compounds upon a surface of the endotracheal tube.

40. The method of claim 37 wherein the step of illuminating the biofilm layer is achieved by an internal illumination of the endotracheal tube.

41. A method of photodynamic eradication of organisms within a biofilm layer of an intravascular catheter, said method comprising the steps of:

providing a photosensitive material and a surfactant to a surface of the intravascular catheter supporting a biofilm layer;

accumulating photosensitive material within organisms comprising the biofilm;

allowing the surfactant to disrupt membranes of organisms within the biofilm;

waiting a period of time until the photosensitive material accumulates within the membranes of organisms within the biofilm;

providing a source of light illumination having predetermined light characteristics; and

illuminating the biofilm layer of the intravascular catheter with the light source to achieve a photodynamic eradication of organisms within the biofilm layer.

42. The method of claim 41 wherein the surfactant is benzalkonium chloride provided at a concentration of between 0.001% to 1.0%.

43. The method of claim 41 wherein the step of providing the photosensitive material and the surfactant is via an impregnation of compounds upon a surface of the intravascular catheter.

44. The method of claim 41 wherein the step of illuminating the biofilm layer is achieved by an internal illumination of the intravascular catheter.