Photocatalytic disinfection of implanted catheters

• US 9,259,513 B2
• Filed: 06/20/2012
• Issued: 02/16/2016
• Est. Priority Date: 06/20/2011
• Status: Active Grant

• Current Assignee: SRI International, Inc., Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: SRI International, Inc.
• Inventors: Bedwell, William, Moro, Lorenza, Arons, Eric A., Garcia, Pablo E., Onugha, Osita, Dutta, Sanjeev, Young, Sarah, Shakespear, Karen F., Haagensen, Janus A. J.
• Primary Examiner(s): CONLEY, SEAN EVERETT
• Application Number:
  US13/528,765
• Publication Number:
  US 20130060188A1
• Time in Patent Office: 1,336 Days
• Field of Search: 604/21, 422/24
• US Class Current: 1/1
• CPC Class Codes: A61L 2/0047 Ultraviolet radiation
• CPC Class Codes: A61L 2202/24 Medical instruments, e.g. endoscopes, catheters, sharps
• CPC Class Codes: A61L 29/106 Inorganic materials other than carbon
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61M 2025/0056 provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
• CPC Class Codes: A61M 25/0017 specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections
• CPC Class Codes: A61M 25/0045 multi-layered, e.g. coated coating materials A61L29/08
• CPC Class Codes: A61M 25/005 with embedded materials for reinforcement, e.g. wires, coils, braids

Abstract

An implantable catheter is provided that may be disinfected without removal from the body of a patient, using a photocatalytic method to activate a reaction on the catheter surface that generates oxidizing agents in the form of Reactive Oxygen Species (“ROS”) and thus destroy microorganisms in a biofilm that is present or forming. A catheter system includes the implantable catheter, a light source, and a source of power operably connected to the light source. Methods are also provided for disinfecting the implantable catheter in vivo.

Claims

1. An implantable catheter that can be photocatalytically disinfected without removal from a patient'"'"'s body, comprising:

an elongate catheter body of predetermined length having a proximal end, a distal end, at least one lumen extending through the catheter body and adapted to transport fluid from the proximal end to the distal end, an outer surface on the exterior of the catheter body, and an inner surface on the interior of the lumen;

an outer photocatalytic layer on the outer surface that undergoes a photocatalysis reaction upon irradiation with ultraviolet light to generate reactive oxygen species;

an out-coupling means for facilitating out-coupling of ultraviolet light directed into the catheter at the proximal end so that along the length of the catheter a first fraction of the light is refracted toward the catheter surfaces and thus toward the outer photocatalytic layer, thereby activating the photocatalysis reaction;

wherein the out-coupling means has a density gradient that increases axially along the length of the catheter from the proximal end to the distal end for ensuring that the amount of out-coupled ultraviolet light is substantially uniform along the length of the catheter from the proximal end to the distal end.

2. The implantable catheter of claim 1, wherein the outer photocatalytic layer is comprised of particulate crystalline titanium dioxide selected from anatase, brookite, rutile, and combinations thereof.

3. The implantable catheter of claim 2, wherein the crystalline titanium dioxide comprises at least 50% anatase.

4. The implantable catheter of claim 3, wherein the crystalline titanium dioxide comprises has a particle size in the range of about 10 nm to about 300 nm.

5. The implantable catheter of claim 3, wherein the particle size is in the range of about 100 nm to about 300 nm.

6. The implantable catheter of claim 1, wherein the outer photocatalytic layer has a thickness in the range of about 20 nm to 1 μ

m.

7. The implantable catheter of claim 1, wherein the outer photocatalytic layer has a thickness in the range of about 20 nm to about 200 nm.

8. The implantable catheter of claim 1, wherein the outer photocatalytic layer is embedded in the outer surface of the catheter and thus integral therewith.

9. The implantable catheter of claim 1, wherein the catheter body comprises a flexible elastomeric material that is substantially transparent to ultraviolet radiation.

10. The implantable catheter of claim 9, wherein the flexible elastomeric material comprises a silicone polymer substantially free of unsaturated bonds.

11. The implantable catheter of claim 1, wherein the out-coupling means comprises scattering particles dispersed in the catheter body along the length thereof.

12. The implantable catheter of claim 1, wherein the out-coupling means comprises a tubular reinforcing element in the catheter body that extends from the proximal end to the distal end and comprises a material that is substantially transparent to the ultraviolet light.

13. The implantable catheter of claim 12, wherein the tubular reinforcing element comprises a braid.

14. The implantable catheter of claim 13, wherein the tubular reinforcing element comprises a helix or weave.

15. The implantable catheter of claim 12, wherein the tubular reinforcing element also serves as a structural support and increases the tear strength of the catheter body.

16. The implantable catheter of claim 12, wherein the tubular reinforcing element is comprised of a material selected from fluoropolymers, poly(vinyl chloride), polyethylene, and polypropylene.

17. The implantable catheter of claim 16, wherein the tubular reinforcing element is comprised of a fluoropolymer.

18. The implantable catheter of claim 17, wherein the fluoropolymer comprises a fluorinated ethylene propylene (FEP) resin.

19. The implantable catheter of claim 17, wherein the fluoropolymer comprises a perfluoroalkoxy copolymer (PFA) resin.

20. The implantable catheter of claim 1, wherein the out-coupling means comprises bubbles in the catheter body along the length thereof extending from the proximal end to the distal end.

21. The implantable catheter of claim 1, wherein the out-coupling means comprises the texturing of the outer wall of the catheter body along the length thereof in a manner that increases the extent of out-coupling from the proximal end to the distal end.

22. The implantable catheter of claim 11, wherein the out-coupling means comprises incorporation of the scattering particles in a density gradient that increases axially along the length of the catheter from the proximal end to the distal end.

23. The implantable catheter of claim 22, wherein the density of scattering particles increases by a factor of about 2 to about 100 from the proximal end to the distal end.

24. The implantable catheter of claim 23, wherein the density of scattering particles increases by a factor of about 5 to about 15 from the proximal end to the distal end.

25. The implantable catheter of claim 12, wherein the out-coupling means comprises incorporation of the tubular reinforcing element in a density gradient that increases axially along the length of the catheter from the proximal end to the distal end.

26. The implantable catheter of claim 11, further including an additional out-coupling means in the form of a tubular reinforcing element in the catheter body that extends from the proximal end to the distal end and comprises a material that is substantially transparent to ultraviolet light.

27. The implantable catheter of claim 1, further including an inner photocatalytic layer on the inner surface that undergoes a photocatalysis reaction upon irradiation with ultraviolet light to generate reactive oxygen species.

28. The implantable catheter of claim 27, wherein the outer photocatalytic layer and the inner photocatalytic layer are comprised of the same material.

29. The implantable catheter of claim 28, wherein the outer photocatalytic layer and the inner photocatalytic layer are comprised of particulate crystalline titanium dioxide selected from anatase, brookite, rutile, and combinations thereof.

30. The implantable catheter of claim 1, further including a light confinement means for ensuring that a second portion of the light is internally reflected and thereby continues to travel axially through the length of the catheter to the distal end.

31. The implantable catheter of claim 30, wherein the light confinement means comprises a cladding layer interposed between the outer surface of the catheter body and the photocatalytic layer.

32. The implantable catheter of claim 31, wherein the cladding layer is comprised of a material having a lower index of refraction than the catheter body.

33. The implantable catheter of claim 32, wherein the cladding layer has a thickness in the range of about 0.002 mm to about 0.5 mm.

34. The implantable catheter of claim 33, wherein the cladding layer has a thickness in the range of about 0.05 mm to about 0.2 mm.

35. The implantable catheter of claim 1, further including a structural reinforcing means for increasing the tear strength of the catheter, the tensile strength of the catheter, the force at break, or any combination thereof.

36. The implantable catheter of claim 1, further including a means for imparting radioopacity to the catheter body to enable visualization of the implanted catheter using medical imaging technology.

37. The implantable catheter of claim 1, wherein the out-coupling means, impart additional radioopacity to the catheter body.

38. The implantable catheter of claim 1, wherein the catheter body is adapted to carry ultraviolet light from the proximal end along its length to the distal end.

39. The implantable catheter of claim 38, further including an additional means for carrying ultraviolet light from the proximal end along its length to the distal end.

40. The implantable catheter of claim 39, wherein the additional light carrying means comprises at least one flexible, substantially UV-transparent fused silica rod, wherein the rod is embedded in the catheter body and extending along the length of the catheter from the proximal end to the distal end, or the rod is wrapped around the catheter in a braid formation or in single or multiple helices.

41. The implantable catheter of claim 39, wherein the additional light carrying means comprises an aqueous liquid in one or more channels in the catheter body that extend along the length of the catheter from the proximal end to the distal end.

51. A method for inhibiting a biofilm on at least the outer surface of the implantable catheter of claim 1, the method comprising, without removing the implantable catheter from a patient'"'"'s body, irradiating the catheter body by directing ultraviolet light from a powered light source into the catheter at the proximal end so as to activate the photocatalysis reaction on at least the outer surface of the catheter along the length thereof, thereby generating a biofilm-inhibiting concentration of reactive oxygen species in the localized region of the catheter surface.

52. The method of claim 51, wherein the photocatalytic surfaces of the catheter are irradiated at a power density in the range of about 1 μ

W/cm² to about 10 mW/cm².

53. The method of claim 51, wherein the biofilm inhibiting comprises killing microorganisms in a biofilm present or forming on at least the outer surface of the implantable catheter.

54. The method of claim 53, wherein the photocatalytic surfaces of the catheter are irradiated at a power density in the range of about 10 μ

W/cm² to about 10 mW/cm².

55. The method of claim 54, wherein the catheter body is irradiated intermittently at approximately regular intervals for a time period in the range of about 2 minutes to about 2 hours.

56. The method of claim 55, wherein the time period is in the range of about 15 minutes to about 1 hour.

57. The method of claim 51, wherein the biofilm inhibiting comprises preventing formation of a biofilm on at least the outer surface of the implantable catheter.

58. The method of claim 57, wherein the photocatalytic surfaces of the catheter are irradiated at a power density in the range of about 1 μ

W/cm² to about 1 mW/cm².

59. The method of claim 58, wherein the power density is in the range of about 1 μ

W/cm² to about 10 μ

W/cm².

60. The method of claim 59, wherein the catheter body is irradiated continuously over an extended time period of at least 72 hours.

61. The method of claim 51, wherein the powered light source is an ultraviolet LED powered by a battery.

62. The method of claim 51, wherein the powered light source is a UV laser or mercury lamp.

63. The method of claim 51, wherein the method further comprises confirming the presence of a biofilm on at least the outer surface of the catheter prior to irradiating the catheter body.

42. An implantable catheter that can be photocatalytically disinfected without removal from a patient'"'"'s body, comprising:

an elongate catheter body of predetermined length having a proximal end, a distal end, at least one lumen extending through the catheter body and adapted to transport fluid from the proximal end to the distal end, an outer surface on the exterior of the catheter body, and an inner surface on the interior of the lumen;

an inner photocatalytic layer on the inner surface that undergoes a photocatalysis reaction upon irradiation with ultraviolet light to generate reactive oxygen species;

an out-coupling means for facilitating out-coupling of ultraviolet light directed into the catheter at the proximal end so that along the length of the catheter a first fraction of the light is refracted toward the catheter surfaces and thus toward the inner photocatalytic layer, thereby activating the photocatalysis reaction;

wherein the out-coupling means has a density gradient that increases axially along the length of the catheter from the proximal end to the distal end for ensuring that the amount of out-coupled ultraviolet light is substantially uniform along the length of the catheter from the proximal end to the distal end.

43. An implantable catheter system, comprising:

an implantable catheter that can be photocatalytically disinfected without removal from a patient'"'"'s body, which comprises;

an elongate catheter body of predetermined length having a proximal end, a distal end, at least one lumen extending through the catheter body and adapted to transport fluid from the proximal end to the distal end, an outer surface on the exterior of the catheter body, and an inner surface on the interior of the lumen;

an outer photocatalytic layer on the outer surface that undergoes a photocatalysis reaction upon irradiation with ultraviolet light to generate reactive oxygen species;

an out-coupling means for facilitating out-coupling of ultraviolet light directed into the catheter at the proximal end so that along the length of the catheter a first portion of the light is refracted toward the catheter surfaces and thus toward the outer photocatalytic layer, thereby activating the photocatalysis reaction;

wherein the out-coupling means has a density gradient that increases axially along the length of the catheter from the proximal end to the distal end for ensuring that the amount of out-coupled ultraviolet light is substantially uniform along the length of the catheter from the proximal end to the distal end;

a light source capable of providing ultraviolet light having a wavelength in the range of about 320 nm to about 387 nm, optically connected to the catheter in a manner effective to enable irradiation of the catheter body with the ultraviolet light; and

a power source operably connected to and capable of powering the light source.

44. The implantable catheter system of claim 43, wherein the light source is selected from a mercury lamp, an LED, and a laser.

45. The implantable catheter system of claim 44, wherein the light source is an LED.

46. The implantable catheter system of claim 45, wherein the power source is a battery.

47. The implantable catheter system of claim 43, wherein the power source is wirelessly connected to the light source and capable of powering the light source remotely.

48. The implantable catheter system of claim 47, wherein the power source includes an inductive powering means and the light source includes a corresponding antenna.

49. The implantable catheter system of claim 43, further including an inner photocatalytic layer on the inner surface that undergoes a photocatalysis reaction upon irradiation with ultraviolet light to generate reactive oxygen species.

50. An implantable catheter system, comprising:

an implantable catheter that can be photocatalytically disinfected without removal from a patient'"'"'s body, which comprises;

an elongate catheter body of predetermined length having a proximal end, a distal end, at least one lumen extending through the catheter body and adapted to transport fluid from the proximal end to the distal end, an outer surface on the exterior of the catheter body, and an inner surface on the interior of the lumen;

an inner photocatalytic layer on the inner surface that undergoes a photocatalysis reaction upon irradiation with ultraviolet light to generate reactive oxygen species;

an out-coupling means for facilitating out-coupling of ultraviolet light directed into the catheter at the proximal end so that along the length of the catheter a first portion of the light is refracted toward the catheter surfaces and thus toward the inner photocatalytic layer, thereby activating the photocatalysis reaction;

wherein the out-coupling means has a density gradient that increases axially along the length of the catheter from the proximal end to the distal end for ensuring that the amount of out-coupled ultraviolet light is substantially uniform along the length of the catheter from the proximal end to the distal end;

a light source capable of providing ultraviolet light having a wavelength in the range of about 320 nm to about 387 nm, optically connected to the catheter in a manner effective to enable irradiation of the catheter body with the ultraviolet light; and

a power source operably connected to and capable of powering the light source.