Apparatus for local drug delivery in limb

• US 20020107504A1
• Filed: 08/09/2001
• Published: 08/08/2002
• Est. Priority Date: 02/06/2001
• Status: Abandoned Application

• Current Assignee: Pharmaspec Corporation
• Original Assignee: Pharmaspec Corporation
• Inventors: Gordon, Lucas S.
• Application Number:
  US09/927,268
• Publication Number:
  US 20020107504A1
• Time in Patent Office: Days
• US Class Current: 604/507
• CPC Class Codes: A61M 31/005 for contrast media

Abstract

A method and system for delivering a medicinal agent to a treatment site within a limb of a patient. An infusion catheter is inserted into a blood vessel and advanced to the treatment site. To prevent blood flow through the treatment site from carrying away the medicinal agent, the blood flow in the limb is stopped by applying external pressure with a constriction device, such as a pressure cuff or a tourniquet, and/or with a balloon on the catheter. The medicinal agent is then injected through the catheter. Optionally, the infusion process is repeated in successive cycles that are separated by a rest period in which blood flow in the limb is allowed to resume. A controller automates the process. Preferably a distal constriction device is used to prevent the medicinal agent from flowing out of the treatment area into tissue distal of the treatment area.

Claims

1. A method for delivering a medicinal agent to a treatment site within a limb of a patient, comprising the steps of:

(a) inserting a catheter into a blood vessel of the patient and advancing the catheter through the blood vessel until a distal tip of said catheter is disposed adjacent to the treatment site;

(b) stopping blood flow within the limb by applying an external pressure to the limb; and

(c) delivering the medicinal agent to the treatment site through the catheter so that the medicinal agent infuses the treatment site and remains at the treatment site at least while the blood flow in the limb is stopped.

2. The method of claim 1, further comprising the steps of:

(a) retaining the medicinal agent at the treatment site for a predetermined perfusion time to allow perfusion of the medicinal agent into tissue proximate the treatment site; and

(b) removing said external pressure to reestablish blood flow in the limb, after the predetermined perfusion time has elapsed.

3. The method of claim 2, wherein the perfusion time is less than about ten minutes.

4. The method of claim 2, further comprising the steps of:

(a) enabling blood flow to resume after the perfusion time, for a predetermined rest period, to reoxygenate tissue within the limb;

(b) again stopping the blood flow within the limb by reapplying the external pressure; and

(c) again delivering the medicinal agent to the treatment site through the catheter.

5. The method of claim 1, wherein the step of stopping blood flow within the limb comprises the step of applying an external pressure around the limb of the patient at a location proximal to the treatment site, said external pressure being sufficient to substantially interrupt blood flow through the limb past the point at which the pressure is applied.

6. The method of claim 5, wherein said external pressure is applied with a tourniquet, and the step of stopping blood flow within the limb further comprises the step of tightening said tourniquet around the limb of the patient at a point on the limb that is proximal to the treatment site.

7. The method of claim 5, wherein said external pressure is applied with a pressure cuff, and wherein the step of stopping blood flow within the limb comprises the step of inflating said pressure cuff around the limb of the patient at a point on the limb that is proximal to the treatment site.

8. The method of claim 5, further comprising the step of isolating said treatment site from a patient'"'"'s tissue distal to said treatment site by applying an external pressure to the limb at a point on the limb that is distal to said treatment site.

9. The method of claim 8, wherein the step of isolating said treatment site comprises the step of inflating a pressure cuff around the limb of the patient at said point that is distal to the treatment site.

10. The method of claim 8, wherein the step of isolating said treatment site comprises the step of tightening a tourniquet around the limb of the patient at said point that distal to the treatment site.

11. The method of claim 1, further comprising the step of removing a substantial amount of fluid from the blood and lymph vessels adjacent to said treatment site by applying an external pressure to the limb in a region that substantially overlies said treatment site, after the step of inserting the catheter and before the step of stopping blood flow within the limb.

12. The method of claim 11, wherein the step of removing a substantial amount of fluid comprises the step of tightening a tourniquet around the limb of the patient at said region that substantially overlies said treatment site.

13. The method of claim 11, wherein the step of removing a substantial amount of fluid comprises the step of inflating a pressure cuff around the limb of the patient at said region that substantially overlies said treatment site.

14. The method of claim 1, further comprising the step of removing a substantial amount of fluid from the blood and lymph vessels adjacent to said treatment site by applying an external pressure to the limb at a region that substantially overlies said treatment site, after the step of inserting a catheter and before the step of stopping blood flow within the limb.

15. The method of claim 1, further comprising the step of displacing any residual medicinal agent back into the catheter from the treatment site by applying an external pressure to the limb at a region that substantially overlies said treatment site, after the step of delivering the medicinal agent to the treatment site.

16. The method of claim 15, wherein the step of displacing any residual medicinal agent comprises the step of tightening a tourniquet around the limb of the patient at said region that substantially overlies said treatment site.

17. The method of claim 15, wherein the step of displacing any residual medicinal agent comprises the step of inflating a pressure cuff around the limb of the patient at said region that substantially overlies said treatment site.

18. The method of claim 1, further comprising the step of applying an external pressure to the limb, over an area that overlies the treatment site and extends beyond said treatment site in both a proximal and a distal direction along the limb.

19. The method of claim 18, wherein the step of applying the external pressure to the limb over the area comprises the step of tightening a tourniquet around the limb of the patient.

20. The method of claim 18, wherein the step of applying the external pressure to the limb over the area comprises the step of inflating a pressure cuff around the limb of the patient.

21. The method of claim 1, wherein the step of inserting the catheter comprises the step of inserting the catheter into a vein of the patient and advancing the catheter in a retrograde direction within the vein until the distal end of the catheter is disposed adjacent to the treatment site.

22. The method of claim 21, wherein said catheter has a balloon disposed proximate the distal tip of said catheter, further comprising the step of isolating said treatment site from a patient'"'"'s tissue distal to said treatment site by inflating the balloon of said catheter.

23. The method of claim 1, further comprising the step of administering to the treatment site a substance known to dilate and separate endothelial cells, thereby increasing a transfer of said medicinal agent across blood vessel walls at the treatment site.

24. The method of claim 23, wherein said substance comprises papaverine.

25. The method of claim 23, wherein said substance is utilized at least one of before, during, and after the step of delivering the medicinal agent to the treatment site.

27. The system of claim 26, further comprising a delivery device connected in fluid communication with a proximal end of the lumen of the infusion catheter, said delivery device being employed to infuse the medicinal agent into the treatment site through the lumen.

28. The system of claim 27, wherein said delivery device comprises an infusion pump.

29. The system of claim 27, wherein said constrictor comprises a pressure actuated cuff, further comprising a controller connected to control operation of said delivery device and said pressure actuated cuff, wherein said controller automatically causes said pressure actuated cuff to stop a blood flow within a limb of a patient, and wherein said controller automatically activates said delivery device, causing the medicinal agent to be infused at the treatment site.

30. The system of claim 29, wherein said controller repetitively activates and deactivates said constrictor and said delivery device so that the medicinal agent is infused into the treatment site during successive cycles.

31. The system of claim 30, wherein said delivery device further comprises a flow sensor that produces a signal indicative of a flow of the medicinal fluid through the lumen, for use in determining a quantity of the medicinal agent delivered to the treatment site, said signal being supplied to the controller for use in controlling the delivery device.

32. The system of claim 29, wherein said controller comprises a timer that determines time intervals, including at least one of:

(a) a pressure time interval during which the controller causes a blood flow to be stopped in a limb of a patient;

(b) a rest time interval between successive cycles; and

(c) a dosage time interval during which the medicinal fluid is infused into the treatment site.

33. The system of claim 26, wherein said constrictor comprises a pressure actuated cuff adapted to wrap around a limb of a patient;

further comprising an inflation pump operatively connected with said controller for receiving an activation signal from said controller, wherein said inflation pump is operatively connected to said cuff to provide a pressurized fluid for inflating said cuff.

34. The system of claim 33, wherein said pressure actuated cuff has a size and shape that enables the pressure actuated cuff to substantially overlap the treatment site, such that when said pressure actuated cuff is inflated, it is adapted to compress the treatment site, thereby forcing a substantial amount of fluid from the blood and lymph vessels within the treatment site.

35. The system of claim 33, wherein said constrictor further comprises a pressure sensor for detecting a pressure applied to the pressure actuated cuff, producing a pressure signal that is indicative of the pressure of the fluid applied to inflate the pressure actuated cuff.

36. The system of claim 29, wherein said controller determines a total dosage of the medicinal agent that is delivered to the treatment site.

37. The system of claim 36, wherein said controller causes the delivery device to deliver a predetermined dosage of the medicinal agent.

38. The system of claim 26, wherein said infusion catheter includes a radio-opaque element disposed adjacent to its distal end to assist in positioning the distal end adjacent to the treatment site.

39. The system of claim 26, wherein said infusion catheter includes an enlarged distal portion adjacent to the distal end of the infusion catheter adapted for sealing against an inner wall of a blood vessel to prevent the medicinal agent from flowing back along the infusion catheter and away from the treatment site.

40. The system of claim 26, wherein said infusion catheter includes a second lumen adapted to receive a guide wire to assist in positioning the distal end of the infusion catheter.

41. The system of claim 26, further comprising an introducer sheath, adapted for insertion into a blood vessel of a patient, to provide a reusable access site for insertion of the infusion catheter.

42. The system of claim 29, further comprising an additional external constrictor that is adapted to exert sufficient constrictive pressure on a limb of a patient at a location distal to said treatment site to prevent a medicinal agent infused into a treatment site from migrating away from said treatment site and into tissue located distal to said treatment site.

43. The system of claim 42, wherein said additional external constrictor comprises another pressure actuated cuff adapted to wrap around a limb of a patient;

further comprising an inflation pump operatively connected to said controller for receiving an activation signal from said controller, and wherein said inflation pump is operatively connected to the other pressure actuated cuff to provide a pressurized fluid for inflating said other pressure actuated cuff.

44. The system of claim 43, wherein the pressure actuated cuffs comprising said constrictor and said additional external constrictor are both inflated by the inflation pump.

45. The system of claim 44, further comprising a valve in fluid communication with said inflation pump and the pressure actuated cuffs comprising said constrictor and said additional external constrictor, said valve being controllably connected to said controller, such that upon receiving an activation signal from said controller, said valve selectively enables one of the pressure actuated cuffs comprising said constrictor and said additional external constrictor to be inflated by said inflation pump.

46. The system of claim 43, further comprising another inflation pump, wherein the pressure actuated cuffs comprising said constrictor and said additional external constrictor are each inflated by a different inflation pump.

47. The system of claim 43, further comprising a fluid displacement cuff having a size and shape sufficient to enable the fluid displacement cuff to substantially overlie the treatment site, such that when said fluid displacement cuff is activated, it is adapted to compress the treatment site, thereby displacing a substantial amount of fluid from blood and lymph vessels proximate to the treatment site.

48. The system of claim 47, further comprising an inflation pump operatively connected to said controller for receiving an activation signal from said controller, wherein said inflation pump is operatively connected to said fluid displacement cuff to provide pressurized fluid for activating the fluid displacement cuff by inflating said fluid displacement cuff with the pressurized fluid.

49. The system of claim 47, further comprising a plurality of inflation pumps, wherein the pressure actuated cuff comprising said constrictor, the pressure actuated cuff comprising said additional external constrictor, and the fluid displacement cuff are each inflated by a different inflation pump.

50. The system of claim 47, further comprising another inflation pump, wherein the actuated cuff comprising said constrictor and the actuated cuff comprising said additional external constrictor are inflated by the same inflation pump, and the fluid displacement cuff is inflated by a different inflation pump.

51. The system of claim 47, wherein the pressure actuated cuff comprising said constrictor, the pressure actuated cuff comprising said additional external constrictor, and the fluid displacement cuff are each inflated by the inflation pump.

52. The system of claim 51, further comprising a valve in fluid communication with said inflation pump and the pressure actuated cuff comprising said constrictor, the pressure actuated cuff comprising said additional external constrictor, and the fluid displacement cuff, said valve being controllably connected to said controller such that upon receiving an activation signal from said controller, said valve selectively enables one of the pressure actuated cuffs and the fluid displacement cuff to be inflated by said inflation pump.

53. The system of claim 52, further comprising a bleed valve in fluid communication with said fluid displacement cuff, said bleed valve being controllably connected to said controller such that upon receiving an activation signal from said controller, said bleed valve enables the fluid displacement cuff to be deflated without also deflating either pressure actuated cuff.

54. The system of claim 26, wherein said infusion catheter includes an inflatable balloon disposed adjacent to the distal end of the infusion catheter and adapted for sealing against an inner wall of a blood vessel to prevent the medicinal agent from flowing back along the infusion catheter and away from the treatment site, and further comprising a balloon inflation pump operatively connected to said controller for receiving an activation signal from said controller, said balloon inflation pump being operatively connected to said infusion catheter to provide a pressurized fluid for inflating said balloon.

26. A system for delivering and retaining a medicinal agent at a treatment site within a patient, comprising:

(a) an infusion catheter having a lumen that extends to a distal end of the infusion catheter from a port disposed adjacent to a proximate end of the catheter, said infusion catheter being adapted for insertion into a blood vessel of a patient and adapted to be advanced to a treatment site; and

(b) an external constrictor that is adapted to exert sufficient constrictive pressure on a limb of a patient to stop blood flow within the limb while a medicinal agent is infused into a treatment site to which the distal end of the catheter has been advanced through a blood vessel of a patient, so that the medicinal agent remains at a treatment site at least while a blood flow in a limb is stopped.

55. A method for controlling delivery of a medicinal agent to a treatment site within a limb of a patient through a catheter that has been inserted into a blood vessel of the patient and advanced to the treatment site, comprising the steps of:

(a) automatically activating a constrictor, causing the constrictor to apply an external pressure to the limb of the patient to stop the flow of blood within the limb; and

(b) automatically activating a delivery device to deliver the medicinal agent to the treatment site through the catheter, said medicinal agent remaining at the treatment site at least while the flow of blood within the limb is stopped.

56. The method of claim 55, further comprising the step of releasing the external pressure applied by the constrictor after a predetermined constriction period of time has elapsed.

57. The method of claim 55, wherein the step of automatically activating the delivery device comprises the step of infusing the medicinal agent for a predetermined infusion period of time.

58. The method of claim 55, further comprising the step of delivering a predetermined dosage of the medicinal agent to the treatment site.

59. The method of claim 55, further comprising the steps of:

(a) detecting a quantity of the medicinal agent delivered to the treatment site; and

(b) determining when to deactivate said delivery device as a function of the quantity of the medicinal agent that has been delivered to the treatment site.

60. The method of claim 55, further comprising the step of deactivating said delivery device once a total desired quantity of the medicinal agent delivered to the treatment site equals a predetermined threshold limit.

61. The method of claim 55, further comprising the steps of:

(a) repeating steps (a) and (b) in a plurality of successive cycles; and

(b) allowing blood flow to resume in the limb for a predetermined rest period between successive cycles.

62. The method of claim 55, further comprising the step of automatically activating a second constrictor disposed at a point on the limb that is distal to treatment site, causing the second constrictor to apply an external pressure to the limb of the patient sufficient to prevent any medicinal agent delivered to said treatment site from migrating to tissue distal to the treatment site, such that said second constrictor is activated whenever the constrictor is activated.

63. The method of claim 55, further comprising the step of automatically activating a fluid displacement cuff that substantially overlies said treatment site before activating the constrictor, causing a substantial volume of fluid to be displaced from the treatment site.

64. The method of claim 63, further comprising the step of automatically activating said fluid displacement cuff after activating a delivery device, causing any residual medicinal agent delivered to the treatment site to be displaced back into said delivery device.

65. A machine readable medium on which are stored machine readable instructions for performing the steps of claim 55.