Method and device for electrochemical formation of therapeutic species in vivo

• US 7,727,221 B2
• Filed: 06/27/2002
• Issued: 06/01/2010
• Est. Priority Date: 06/27/2001
• Status: Active Grant

• Current Assignee: Remon Medical Technologies Ltd. (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Penner, Avi, Gileadi, Eilezer
• Primary Examiner(s): BOCKELMAN, MARK
• Application Number:
  US10/477,514
• Publication Number:
  US 20040230225A1
• Time in Patent Office: 2,896 Days
• Field of Search: 604/20, 607/2, 607/75, 607/50, 623 11- 154
• US Class Current: 604/500
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices

Abstract

A device and method are provided for spontaneous electrochemical production of therapeutic species, in vivo. An active metal is implanted in the tissue. The metal undergoes corrosion, thus acting as a reducing agent to constituents in the tissue, so as to cause these constituents to form the therapeutic agents.

Claims

1. A method of producing a therapeutic agent in a body, the method comprising:

electrochemically converting at least one substance present in a body fluid flowing in a body lumen into a therapeutic agent by implanting a tubular implant in the body lumen, the implant comprising an uncoated portion and a coated portion, the coated portion coated with an active metal, for electrochemically converting at least one substance present in a body fluid flowing in the body lumen into a therapeutic agent, wherein the implant is implanted with the body lumen such that one of the uncoated portion and the coated portion is disposed upstream of the other relative to the flow of the body fluid in the body lumen, wherein the coated portion and the uncoated portion are directly exposed to the flow of body fluid.

2. The method of claim 1, wherein the electrochemically converting at least one substance present in the body fluid into the therapeutic agent comprises direct conversion.

3. The method of claim 1, wherein the electrochemically converting at least one substance present in the body fluid into the therapeutic agent comprises indirect conversion.

4. The method of claim 1, wherein the at least one substance is a normal body fluid constituent.

5. The method of claim 4, wherein the normal body fluid constituent is selected from the group consisting of water, molecular oxygen, nitrite and nitrate ions and L-arginine.

6. The method of claim 1, wherein the at least one substance is administered to the body.

7. The method of claim 6, wherein the at least one substance is administered to the body through a diet.

8. The method of claim 6, wherein the at least one substance is administered to the body through a medical administration.

9. The method of claim 6, wherein the at least one substance is selected from the group consisting of nitrite ion, nitrate ions, and a combination thereof.

10. The method of claim 1, wherein the therapeutic agent is an oxidizing agent.

11. The method of claim 1, wherein the therapeutic agent is nitric oxide.

12. The method of claim 1, wherein the active metal comprises zinc.

13. The method of claim 1, wherein the active metal comprises iron.

14. The method of claim 1, wherein the implant is a stent formed of a biologically inert metal, the coated portion operative as an anode, and the uncoated portion operative as a cathode.

15. The method of claim 14, wherein the implant is implanted with the portion coated with the active metal downstream of the uncoated portion, so that the therapeutic agents produced at the cathode migrate downstream with the body fluid to effect therapy at the anode.

16. The method of claim 14, wherein the coated and uncoated portions are equally distributed along a length and a width of the stent.

17. The method of claim 14, wherein the uncoated portion is further operative as a catalyst to the conversion.

18. The method of claim 1, wherein the implant is implanted with the coated portion downstream of the uncoated portion so that the therapeutic agents produced at the cathode migrate downstream with the body fluid to effect therapy at the anode.

19. The method of claim 1, wherein the uncoated portion is further operative as a catalyst to the conversion.

20. The method of claim 1, wherein the body lumen is a blood vessel.

21. The method of claim 1, wherein the body lumen is a renal artery.

22. The method of claim 1, wherein the body lumen is located in brain tissue.

23. The method of claim 1, wherein the body lumen is located in cancerous tissue.

24. The method of claim 1, wherein the body lumen is a blood vessel feeding a cancerous tissue.

25. The method of claim 1, wherein the body lumen is a blood vessel feeding tissue for which therapeutic treatment is desired.

26. The method of claim 1, wherein the uncoated portion is formed of biologically inert metal.

27. The method of claim 26, wherein the uncoated portion is operative as a cathode and the coated portion is operative as an anode.

28. The method of claim 27, wherein the implant is implanted within the body lumen, such that the cathode is disposed upstream of the anode.

29. The method of claim 1, wherein the implant is implanted within the body lumen, such that the uncoated portion is disposed upstream of the coated portion.

30. The method of claim 1, wherein the implant includes a cylindrical wall having an exterior surface opposite the interior surface for being placed into contact with the body lumen.

31. A method of producing an oxidizing agent in a body, the method comprising:

electrochemically converting at least one substance present in a body fluid flowing in a body lumen into an oxidizing agent by implanting a tubular implant in the body lumen, the implant being partially coated with an active metal, thereby forming a coated portion of the implant and an uncoated portion of the implant for electrochemically converting at least one substance present in a body fluid flowing the body lumen into an oxidizing agent, wherein the implant is implanted within the body lumen such that one of the uncoated portion and the coated portion is disposed upstream of the other relative to the flow of the body fluid in the body lumen, wherein the coated portion and the uncoated portion are directly exposed to the flow of body fluid.

32. The method of claim 31, wherein the electrochemically converting the at least one substance present in the body fluid into the oxidizing agent comprises direct conversion.

33. The method of claim 31, wherein the electrochemically converting the at least one substance present in the body fluid into the oxidizing agent comprises indirect conversion.

34. The method of claim 31, wherein the at least one substance is a normal body fluid constituent.

35. The method of claim 34, wherein the normal body fluid constituent is selected from the group consisting of water and molecular oxygen.

36. The method of claim 31, wherein the active metal comprises zinc.

37. The method of claim 31, wherein the active metal comprises iron.

38. The method of claim 31, wherein the implant is a stent formed of a biologically inert metal partially coated with the active metal.

39. The method of claim 38, wherein the coated portion is operative as an anode, and the uncoated portion is operative as a cathode.

40. The method of claim 39, wherein the implant is implanted with the coated portion downstream of the uncoated portion, so that the oxidizing agents produced at the cathode migrate downstream with the body fluid to effect therapy at the anode.

41. The method of claim 39, wherein the coated and uncoated portions are equally distributed along a length and a width of the stent.

42. The method of claim 31, wherein the implant is a stent formed of a biologically inert material, the stent having a piece of the active metal attached thereto.

43. The method of claim 31, wherein the coated portion is operative as an anode, and the uncoated portion is operative as a cathode.

44. The method of claim 43, wherein the implant is implanted with the portion downstream of the uncoated portion so that oxidizing agents produced at the cathode migrate downstream with the body fluid to effect therapy at the anode.

45. The method of claim 43, wherein the coated and uncoated portions are equally distributed along a length and a width of the implant.

46. The method of claim 31, wherein the implant includes a cylindrical wall having an exterior surface opposite the interior surface for being placed into contact with the body lumen.

47. A method of reducing cell proliferation in a tissue, the method comprising electrochemically converting at least one substance present in a body fluid flowing in a body lumen into an oxidizing agent by implanting a tubular implant in the body lumen, the implant being partially coated with an active metal, thereby forming a coated portion of the implant and an uncoated portion of the implant for electrochemically converting at least one substance present in a body fluid flowing in the body lumen into an oxidizing agent in an amount sufficient for reducing cell proliferation in the body lumen, wherein the implant is implanted within the body lumen such that one of the uncoated portion and the coated portion is disposed upstream of the other relative to the flow of the body fluid in the body lumen, wherein the coated portion and the uncoated portion are directly exposed to the flow of body fluid.

48. The method of claim 47, wherein the electrochemically converting the at least one substance present in the body fluid into the therapeutic agent comprises direct conversion.

49. The method of claim 47, wherein the electrochemically converting the at least one substance present in the body fluid into the oxidizing agent comprises indirect conversion.

50. The method of claim 47, wherein the at least one substance is a normal body fluid constituent.

51. The method of claim 50, wherein the normal body fluid constituent is selected from the group consisting of water, and molecular oxygen.

52. The method of claim 47, wherein the active metal comprises zinc.

53. The method of claim 47, wherein the active metal comprises iron.

54. The method of claim 47, wherein the implant is a stent formed of a biologically inert metal partially coated with the active metal.

55. The method of claim 47, wherein the implant is a stent formed of a biologically inert metal, having:

a portion coated with the active metal, operative as an anode; and

an uncoated portion, operative as a cathode.

56. The method of claim 55, wherein the implant is implanted with the coated portion downstream of the uncoated portion, so that the oxidizing agents, produced at the cathode migrate downstream with the body fluid to effect therapy at the anode.

57. The method of claim 55, wherein the coated and uncoated portions are equally distributed along a length and a width of the stent.

58. The method of claim 47, wherein the implant is a stent formed of a biologically inert material, the stent having a piece of the active metal attached thereto.

59. The method of claim 47, wherein the coated portion is operative as an anode, and an uncoated portion is operative as a cathode.

60. The method of claim 59, wherein the implant is implanted with the coated portion downstream of the uncoated portion, so that the oxidizing agents produced at the cathode migrate downstream with the body fluid to effect therapy at the anode.

61. The method of claim 59, wherein the coated and uncoated portions are equally distributed along a length and a width of the implant.

62. The method of claim 47, wherein the implant includes a cylindrical wall having an exterior surface opposite the interior surface for being placed into contact with the body lumen.

63. A method of producing nitric oxide in a body, the method comprising:

electrochemically converting at least one substance present in a body fluid flowing in a body lumen into nitric oxide by implanting a tubular implant in the body lumen, the implant being partially coated with an active metal, thereby forming a coated portion of the implant and an uncoated portion of the implant for electrochemically converting at least one substance present in a body fluid flowing the body lumen into the nitric oxide, wherein the implant is implanted within the body lumen such that one of the uncoated portion and the coated portion is disposed upstream of the other relative to the flow of the body fluid in the body lumen, wherein the coated portion and the uncoated portion are directly exposed to the flow of body fluid.

64. The method of claim 63, wherein the nitric oxide is operative as a vasodilating agent.

65. The method of claim 63, wherein the electrochemically converting the at least one substance present in the body fluid into the nitric oxide comprises direct conversion.

66. The method of claim 63, wherein the electrochemically converting the at least one substance present in the body fluid into the nitric oxide comprises indirect conversion.

67. The method of claim 63, wherein the at least one substance is a normal body fluid constituent.

68. The method of claim 67, wherein the normal body fluid constituent is selected from the group consisting of nitrite and nitrate ions and L-arginine.

69. The method of claim 63, wherein the at least one substance is administered to the body.

70. The method of claim 69, wherein the at least one substance is administered to the body through a diet.

71. The method of claim 69, wherein the at least one substance is administered to the body through a medical administration.

72. The method of claim 69, wherein the at least one substance is selected from the group consisting of nitrite ion, nitrate ions, and a combination thereof.

73. The method of claim 63, wherein the active metal comprises zinc.

74. The method of claim 63, wherein the active metal comprises iron.

75. The method of claim 63, wherein the implant comprises a stent formed of a biologically inert metal partially coated with the active metal.

76. The method of claim 63, wherein the implant is a stent formed of a biologically inert metal, the coated portion operative as an anode, and the uncoated portion operative as a cathode.

77. The method of claim 76, wherein the implant is implanted with the coated portion downstream of the uncoated portion, so that nitric oxide, produced at the cathode migrates downstream with the body fluid, to effect therapy at the anode.

78. The method of claim 76, wherein the coated and uncoated portions are equally distributed along a length and a width of the stent.

79. The method of claim 63, wherein the implant is a stent formed of a biologically inert material, the stent having a piece of the active metal attached thereto.

80. The method of claim 63, wherein the coated portion is operative as an anode, and the uncoated portion is operative as a cathode.

81. The method of claim 80, wherein the implant is implanted with the coated portion downstream of the uncoated portion, so that the nitric oxide produced at the cathode migrates downstream with the body fluid to effect therapy at the anode.

82. The method of claim 80, wherein the coated and uncoated portions are equally distributed along a length and a width of the implant.

83. The method of claim 63, wherein the implant includes a cylindrical wall having an exterior surface opposite the interior surface for being placed into contact with the body lumen.