Electrochemical disinfection of implanted catheters

• US 9,320,832 B2
• Filed: 06/20/2012
• Issued: 04/26/2016
• 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., Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Joseph, Jose P., Garcia, Pablo E., Shakespear, Karen F., Young, Sarah, Haagensen, Janus A. J., Dutta, Sanjeev
• Primary Examiner(s): Conley, Sean E
• Assistant Examiner(s): Spamer, Donald
• Application Number:
  US13/528,788
• Publication Number:
  US 20130041238A1
• Time in Patent Office: 1,406 Days
• Field of Search: 422/28, 422/29
• US Class Current: 1/1
• CPC Class Codes: A61L 2/03 Electric current
• CPC Class Codes: A61L 2202/11 Apparatus for generating biocidal substances, e.g. vaporisers, UV lamps
• CPC Class Codes: A61L 2202/24 Medical instruments, e.g. endoscopes, catheters, sharps
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 29/02 Inorganic materials
• CPC Class Codes: A61L 29/04 Macromolecular materials
• CPC Class Codes: A61L 29/041 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/126 having a macromolecular matrix
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61M 2025/0019 Cleaning catheters or the like, e.g. for reuse of the device, for avoiding replacement
• 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: A61N 1/205 for promoting a biological process

Abstract

An implantable catheter is provided that may be disinfected without removal from the body of a patient, using an electrochemical method to generate an electric field on the catheter surface and thus destroy microorganisms in a biofilm that is present or forming. A catheter system includes the implantable catheter and a voltage source that is operably connected to electrodes on or embedded in the exterior and optionally the interior catheter surface. Methods are also provided for disinfecting the implantable catheter in vivo and for detecting or confirming the presence of a pathogenic biofilm thereon.

Claims

1. A method for electrochemically disinfecting a catheter implanted in a patient'"'"'s body, by creating a biofilm-inhibiting concentration of oxidizing agents, the catheter comprising:

an elongate catheter body comprising a dielectric material and having a proximal region, a distal region, a lumen extending through the catheter body and adapted to transport fluid from the proximal region to the distal region, an outer surface on the exterior of the catheter body, and an inner surface on the interior of the lumen, and

at least two exterior electrodes on and integral with the outer surface of the catheter, the exterior electrodes being elongate and extending longitudinally along the outer surface of the catheter body from the proximal region to the distal region, wherein the exterior electrodes extend radially inward from the outer surface through a wall of the catheter body to the inner surface, thereby additionally serving as interior electrodes;

wherein the two exterior electrodes are separated by a pair of gaps, each gap comprising the dielectric material of the catheter body, and extending radially from the outer surface to the inner surface of the catheter body and longitudinally from the proximal region to the distal region;

the method comprising, in the absence of an added biocidal agent, with the catheter implanted in the patient'"'"'s body, and without removing the catheter from the patient'"'"'s body, applying a voltage across the exterior electrodes of a magnitude that is effective to create a biofilm-inhibiting concentration of oxidizing agents from endogenous compounds present in the body.

2. The method of claim 1 wherein the exterior electrodes comprise an anode and a cathode serving as a working electrode and a counter electrode, and the exterior electrodes further include a third electrode which serves as a reference electrode.

3. The method of claim 1 wherein the catheter body is comprised of a flexible elastomeric material.

4. The method of claim 1 wherein the catheter body is comprised of a flexible elastomeric material comprising silicone, polyurethane, polyvinyl chloride, polyethylene or latex.

5. The method of claim 1 wherein the catheter body is comprised of a flexible elastomeric material comprising silicone or polyurethane.

6. The method of claim 1 wherein the electrodes are metallic.

7. The method of claim 1 wherein the electrodes are comprised of a carbon-polymer composite.

8. The method of claim 1 wherein the electrodes are comprised of a carbon-polymer composite comprising carbon particles and a thermosetting or thermoplastic polymer.

9. The method of claim 1 wherein each gap is in the range of about 1000 Å

to about 2 μ

m.

10. The method of claim 1 wherein each gap is in the range of about 10 μ

m to about 200 μ

m.

11. The method of claim 1 wherein the exterior electrodes have a thickness in the range of about 500 Å

to about 30 μ

m.

12. The method of claim 1 wherein the catheter has a plurality of exterior electrodes comprising a plurality of anodes and an equal number of cathodes.

13. The method of claim 1 wherein the catheter is a central venous catheter implanted in a vein.

14. The method of claim 1 wherein the catheter comprises a biofilm present or forming on at least the outer surface of the catheter, and the applying step kills microorganisms of the biofilm.

15. The method of claim 1 wherein the voltage is provided by a voltage source selected from a direct current source, an alternating current source, and a pulsed voltage source, wherein the source is in electrical communication with the electrodes.

16. The method of claim 1 wherein the voltage source is an alternating current source.

17. The method of claim 1 wherein the voltage source is a direct current source, and polarity is alternated throughout an extended time period such that each electrode alternates between functioning as an anode and functioning as a cathode.

18. The method of claim 1 wherein the voltage source is a direct current source, and polarity is alternated throughout an extended time period such that each electrode alternates between functioning as an anode and functioning as a cathode, wherein the polarity is alternated every five to thirty minutes.

19. The method of claim 1 wherein the voltage is provided by a voltage source that is a direct current source in the form of a portable battery pack.

20. The method of claim 1 wherein the voltage is applied intermittently at regular intervals for a time period in the range of about 15 minutes to about 6 hours.

21. The method of claim 1 wherein the voltage is applied intermittently at regular intervals for a time period in the range of about 30 minutes to about 3 hours.

22. The method of claim 1 wherein the voltage is applied continuously for an extended time period of at least 72 hours.

23. The method of claim 1 wherein the voltage is applied continuously for an extended time period of at least 72 hours, wherein the magnitude of the voltage is in the range of about 0.3 V to about 1.3 V.

24. The method of claim 1 wherein the voltage is applied continuously for an extended time period of at least 72 hours, wherein the magnitude of the voltage is in the range of about 0.3 V to about 0.7 V.

25. The method of claim 1 wherein the voltage is applied continuously for an extended time period of at least 72 hours, wherein the magnitude of the voltage is in the range of about 0.2 V to about 1.0 V.

26. The method of claim 1 wherein the voltage is applied continuously for an extended time period of at least 72 hours, wherein the voltage applied results in a current density in the range of about 5 μ

A/cm² to about 50 μ

A/cm² on at least the outer surface of the catheter body.

27. The method of claim 1 wherein the magnitude of the voltage is in the range of about 0.5 V to about 1.5 V.

28. The method of claim 1 wherein the magnitude of the voltage is in the range of about 0.6 V to about 1.2 V.

29. The method of claim 1 wherein the magnitude of the voltage is in the range of about 0.8 V to about 1.2 V.

30. The method of claim 1 wherein the voltage applied results in a current density in the range of about 5 μ

A/cm² to about 200 μ

A/cm² on at least the outer surface of the catheter body.

31. The method of claim 1 wherein the voltage applied results in a current density in the range of about 10 μ

A/cm² to about 200 μ

A/cm² on at least the outer surface of the catheter body.

32. The method of claim 1 wherein the voltage applied results in a current density in the range of about 20 μ

A/cm² to about 200 μ

A/cm² on at least the outer surface of the catheter body.

33. The method of claim 1 further comprising determining blood oxygen concentration at the outer surface.

34. The method of claim 1 further comprising measuring impedance across the exterior electrodes and communicating the measurement to an external device.

35. The method of claim 1 wherein the method further comprises confirming the presence or formation of a biofilm on at least the outer surface of the catheter prior to applying a voltage across the external electrodes.

36. The method of claim 1 wherein the method further comprises confirming the presence or formation of a biofilm on at least the outer surface of the catheter prior to applying a voltage across the external electrodes, wherein the confirming comprises detecting an increase in impedance across the external electrodes relative to the impedance across the electrodes in the absence of a biofilm.

37. The method of claim 1 wherein the method further comprises confirming the presence or formation of a biofilm on at least the outer surface of the catheter prior to applying a voltage across the external electrodes, wherein the confirming comprises detecting an increase in impedance across the external electrodes relative to the impedance across the electrodes in the absence of a biofilm, wherein the detecting of an increase in impedance comprises applying a voltage in the range of about 10 mV to about 30 mV across the external electrodes while measuring the impedance across the electrodes, and comparing the impedance measured with the impedance observed across the electrodes in the absence of a biofilm.

38. The method of claim 1 wherein the method further comprises confirming the presence or formation of a biofilm on at least the outer surface of the catheter prior to applying a voltage across the external electrodes, and then measuring the thickness of the biofilm present.

39. The method of claim 1 wherein the method further comprises confirming the presence or formation of a biofilm on at least the outer surface of the catheter prior to applying a voltage across the external electrodes, and then measuring the thickness of the biofilm present, and then adjusting the magnitude and duration of voltage applied to ensure that the biofilm is destroyed.

40. The method of claim 1 wherein the method further comprises confirming the presence or formation of a biofilm on at least the outer surface of the catheter prior to applying a voltage across the external electrodes, wherein the confirming comprises detecting a decrease in the amount of oxygen present in the region of the outer surface of the catheter.

41. The method of claim 1 wherein:

the catheter body is comprised of a flexible elastomeric material comprising silicone or polyurethane; and

the electrodes are comprised of a carbon-polymer composite.

42. The method of claim 1 wherein:

the catheter body is comprised of a flexible elastomeric material comprising silicone or polyurethane;

the electrodes are comprised of a carbon-polymer composite, and

each gap is in the range of about 1000 Å

to about 2 μ

m.

43. The method of claim 1 wherein:

the catheter body is comprised of a flexible elastomeric material comprising silicone or polyurethane;

the electrodes are comprised of a carbon-polymer composite, and

each gap is in the range of about 10 μ

m to about 200 μ

m.

44. The method of claim 1 wherein the electrodes extend through the catheter body to a distal terminus of the catheter.

45. The method of claim 1 wherein:

the catheter body is comprised of a flexible elastomeric material comprising silicone or polyurethane;

the electrodes are comprised of a carbon-polymer composite; and

the electrodes extend through the catheter body to a distal terminus of the catheter.

46. The method of claim 1 wherein:

the catheter body is comprised of a flexible elastomeric material comprising silicone or polyurethane;

the electrodes are comprised of a carbon-polymer composite,

each gap is in the range of about 1000 Å

to about 2 μ

m; and

the electrodes extend through the catheter body to a distal terminus of the catheter.

47. The method of claim 1 wherein:

the catheter body is comprised of a flexible elastomeric material comprising silicone or polyurethane;

the electrodes are comprised of a carbon-polymer composite;

each gap is in the range of about 10 μ

m to about 200 μ

m; and

the electrodes extend through the catheter body to a distal terminus of the catheter.

48. The method of claim 1 wherein:

the catheter body is comprised of a flexible elastomeric material comprising silicone or polyurethane;

the electrodes are comprised of a carbon-polymer composite;

each gap is in the range of about 10 μ

m to about 200 μ

m;

and

the electrodes extend through the catheter body to a distal terminus of the catheter, wherein the method effectively inhibits the biofilm at the distal region of the catheter.