Methods and kits for delivering pharmaceutical agents into the coronary vascular adventitia

• US 20030171734A1
• Filed: 01/22/2003
• Published: 09/11/2003
• Est. Priority Date: 01/22/2002
• Status: Abandoned Application

• Current Assignee: Mercator MedSystems, Inc.
• Original Assignee: EndoBionics, Inc.
• Inventors: Seward, Kirk Patrick, Barr, Lynn Mateel, Cafferata, Robert, Wilber, Judith Carol
• Application Number:
  US10/350,314
• Publication Number:
  US 20030171734A1
• Time in Patent Office: Days
• US Class Current: 604/506
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/422 Anti-atherosclerotic agents
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/0093 wherein at least one needle is a microneedle
• CPC Class Codes: A61M 2025/0096 being laterally outward extensions or tools, e.g. hooks or fibres
• CPC Class Codes: A61M 2025/1086 having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves
• CPC Class Codes: A61M 25/0084 being one or more injection needles
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

Methods and kits for delivering pharmaceutical agents to the adventitia surrounding a blood vessel utilize a catheter having a microneedle. The microneedle is positioned in the perivascular space and delivers an amount of pharmaceutical agent sufficient to circumferentially permeate around the blood vessel and, in many cases, extend longitudinally along the blood vessel and in some cases to the adventitia surrounding other blood vessels.

Claims

1. A method for distributing a pharmaceutical agent in the adventitial tissue of a living vertebrate host, said method comprising:

positioning a microneedle through the wall of a blood vessel so that an aperture of the microneedle is positioned in a perivascular space surrounding the blood vessel; and

delivering an amount of the pharmaceutical agent into the perivascular space so that the agent distributes substantially completely circumferentially through adventitial tissue surrounding the blood vessel at the site of the microneedle.

2. A method as set in claim 1, wherein the agent distributes longitudinally along the blood vessel over a distance of at least 1 cm or within a time period no greater than 60 minutes.

3. A method as in claim 2, wherein the concentration of agent in the adventitia at a location spaced 2 cm longitudinally from the delivery site is at least 10% of the concentration at the delivery site.

4. A method as in claim 1, wherein the agent distributes into regions of the adventitia surrounding other blood vessels.

5. A method as in claim 1, wherein the aperture of the microneedle is positioned at a distance from the blood vessel wall equal to at least 10% of the mean luminal diameter of the blood vessel at the microneedle site.

6. A method as in claim 5, wherein the distance is from 10% to 75% of the mean luminal diameter.

7. A method as in claim 1, wherein the amount of the pharmaceutical agent is in the range from 10 μ

l to 5000 μ

l.

8. A method as in claim 1, wherein the agent distributes from the adventitia transmurally back into the intima.

9. A method as in claim 1, wherein the blood vessel is a coronary blood vessel.

10. A method as in claim 9, wherein the coronary blood vessel is an artery.

11. A method as in claim 10, wherein the coronary artery is at risk of hyperplasia.

12. A method as in claim 10, wherein the coronary artery has regions of vulnerable plaque.

13. A method as in claim 1, wherein the patient is suffering from congestive heart failure or a cardiac arrhythmia.

14. A method for depoting a pharmaceutical agent in the adventitial tissue of a living vertebrate host'"'"'s heart, said method comprising:

positioning a microneedle through the wall of a coronary blood vessel so that an aperture of the microneedle is positioned in a perivascular space surrounding the blood vessel; and

delivering an amount of the pharmaceutical agent into the perivascular space so that the agent distributes within adventitial tissue surrounding the blood vessel to provide a depot of agent which is released back into the blood vessel wall over time.

15. A method as in claim 14, wherein the pharmaceutical agent is selected from the group consisting of antiproliferative agents, immunosuppressive agents, anti-inflammatory agents, macrolilde antibiotics, statins, anti-sense agents, metalloproteinase inhibitors, and cell cycle inhibitors and modulators.

16. A method as set in claim 14, wherein the pharmaceutical agent distributes longitudinally along the blood vessel over a distance of at least 1 cm or within a time period no greater than 60 minutes.

17. A method as in claim 16, wherein the concentration of pharmaceutical agent in the adventitia at a location spaced 2 cm longitudinally of the delivery site is at least 10% of the concentration at the delivery site.

18. A method as in claim 14, wherein the pharmaceutical agent distributes into regions of the adventitia surrounding other blood vessels.

19. A method as in claim 14, wherein the aperture of the microneedle is positioned at a distance from the blood vessel wall equal to at least 10% of the mean luminal diameter of the blood vessel at the microneedle site.

20. A method as in claim 19, wherein the distance is from 10% to 75% of the mean luminal diameter.

21. A method as in claim 14, wherein the amount of the pharmaceutical agent is in the range from 10 μ

l to 5000 μ

l.

22. A method as in claim 14, wherein the coronary blood vessel is an artery.

23. A method as in claim 22, wherein the coronary artery is at risk of hyperplasia.

24. A method as in claim 22, wherein the coronary artery has regions of vulnerable plaque.

25. A method for delivering a pharmaceutical agent to a diseased treatment region in a blood vessel of a living vertebrate host, said method comprising:

positioning a microneedle through the wall of a blood vessel at a delivery site away from the diseased treatment region, and

delivering an amount of the pharmaceutical agent through an aperture in the microneedle into a perivascular space surrounding the delivery site so that the agent distributes into adventitial tissue surrounding the diseased treatment region.

26. A method as in claim 25, wherein the microneedle is positioned in the same blood vessel as the diseased treatment region at a location spaced longitudinally away from the diseased treatment region.

27. A method as in claim 25, wherein the microneedle is positioned in a different blood vessel than is the diseased treatment region.

28. A method as in claim 25, wherein the diseased treatment region has been stented and the delivery site is spaced away from the stent.

29. A method as set in claim 25, wherein the agent distributes longitudinally along the blood vessel over a distance of at least 1 cm or within a time period no greater than 60 minutes.

30. A method as in claim 29, wherein the concentration of agent in the adventitia at a location spaced 2 cm longitudinally of the delivery site is at least 10% of the concentration at the delivery site.

31. A method as in claim 25, wherein the agent distributes into regions of the adventitia surrounding other blood vessels.

32. A method as in claim 25, wherein the aperture of the microneedle is positioned at a distance from the blood vessel wall equal to at least 10% of the mean luminal diameter of the blood vessel at the microneedle site.

33. A method as in claim 30, wherein the distance is from 10% to 75% of the mean luminal diameter.

34. A method as in claim 25, wherein the amount of the pharmaceutical agent is in the range from 10 μ

l to 5000 μ

l.

35. A method as in claim 25, wherein the coronary blood vessel is an artery.

36. A method as in claim 25, wherein the coronary artery is at risk of hyperplasia.

37. A method as in claim 25, wherein the coronary artery has regions of vulnerable plaque.

38. A kit for delivering a pharmaceutical agent to a patient suffering from or at risk of vascular disease, said kit comprising:

a catheter having a microneedle which can be advanced from a blood vessel lumen through a wall of the blood vessel to position an aperture of the microneedle in a perivascular space surrounding the blood vessel; and

instructions for use of the catheter according to the following method;

positioning the microneedle through the wall of the blood vessel so that the aperture of the microneedle is located in a perivascular space surrounding the blood vessel; and

delivering an amount of the pharmaceutical agent into the perivascular space so that the agent distributes substantially completely circumferentially through adventitial tissue surrounding the blood vessel at the site of the microneedle.

39. A kit for delivering a pharmaceutical agent to a patient suffering from vascular disease characterized by a diseased treatment region in a blood vessel, said kit comprising:

a catheter having a microneedle which can be advanced from a blood vessel lumen through a wall of the blood vessel to position an aperture of the microneedle in a perivascular space surrounding the blood vessel; and

instructions for use of the catheter according to the following method;

positioning the microneedle through the wall of the blood vessel at a delivery site away from the diseased treatment region; and

delivering an amount of the pharmaceutical agent through an aperture in the microneedle into a perivascular space surrounding the delivery site so that the agent distributes into adventitial tissue surrounding the diseased treatment site.

40. A kit for delivering a pharmaceutical agent to a patient suffering from or at risk of vascular disease, said kit comprising:

a catheter having a microneedle which can be advanced from a blood vessel lumen through a wall of the blood vessel to position an aperture of the microneedle in a perivascular space surrounding the blood vessel; and

instructions for use of the catheter according to the following method;

positioning the microneedle through the wall of the blood vessel so that the aperture of the microneedle is located in a perivascular space surrounding the blood vessel; and

delivering an amount of a lipophilic pharmaceutical agent into the perivascular space so that the lipophilic agent distributes within the lipd-rich adventitial tissue surrounding the blood vessel to provide a depot of agent which is released back into the blood vessel wall over time.

41. The use of a catheter having a microneedle in the manufacture of apparatus for delivering pharmaceutical agents to a patient suffering from vascular disease wherein the pharmaceutical agent is delivered from a blood vessel lumen into a perivascular space surrounding the blood vessel so that the agent distributes circumferentially through adventitial tissue surrounding the blood vessel.

42. The use of a catheter as in claim 41, wherein the agent distributes longitudinally along the blood vessel over a distance of at least 1 cm within a time period no greater than 60 minutes.

43. The use of a catheter as in claim 42, wherein the agent distributes into regions of the adventitia surrounding other blood vessel.