Drug delivery device and method for bi-directional drug delivery

• US 20040249449A1
• Filed: 06/05/2003
• Published: 12/09/2004
• Est. Priority Date: 06/05/2003
• Status: Active Grant

• Current Assignee: Microport Cardiovascular LLC (MicroPort Scientific Corp.)
• Original Assignee: Conor Medsystems Incorporated
• Inventors: Shanley, John F., Parker, Theodore L.
• Granted Patent: US 7,169,179 B2
• Time in Patent Office: Days
• US Class Current: 623/1.43
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91541 Adjacent bands are arranged out of phase
• CPC Class Codes: A61F 2002/91558 connected peak to peak
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir

Abstract

A drug delivery device is provided with openings for directional delivery of a plurality of therapeutic agents to blood vessels or other lumens or organs. In particular, the invention relates to the delivery of different therapeutic agents, different quantities of therapeutic agents, or different release profiles of the same or different therapeutic agents in different directions from the drug delivery device. The invention is useful, for example, for delivering antirestenotic, antithrombotic, antiplatelet, antiproliferative, antineoplastic, immunosuppressive, angiogenic, anti-inflammatory, or antiangiogenic agents and/or vasodilators to a blood vessel. In one embodiment, antiproliferative, antineoplastic, angiogenic, antiangiogenic, anti-inflammatory, and/or antirestenotic agents are delivered to the wall of a blood vessel and antithrombotic agents, antiplatelet agents, and/or vasodilators are delivered to the lumen of a blood vessel.

Claims

1. A method of delivering therapeutic agents comprising the steps of:

a) providing a medical device comprising an exterior surface and an interior surface, and first and second therapeutic agents in openings in the medical device;

b) implanting the medical device with the therapeutic agents in a patient;

c) releasing the first therapeutic agent predominantly in a direction of said exterior surface of the medical device over a time period sufficient to produce a therapeutic effect; and

d) releasing the second therapeutic agent predominantly in a direction of said interior surface of the medical device over a time period sufficient to produce a therapeutic effect.

2. The method of claim 1, wherein the openings in the medical device are through openings traversing the exterior surface and the interior surface.

3. The method of claim 1, wherein the openings in the medical device are non-traversing recesses in the exterior surface or the interior surface of the medical device.

4. The method of claim 2, wherein the first and second therapeutic agents are selected from the group consisting of:

a) different therapeutic agents;

b) different concentrations of therapeutic agents;

c) different release profiles of therapeutic agents; and

d) combinations of a)-c).

5. The method of claim 1, wherein the openings are provided with a barrier layer disposed at a radially intermediate location with respect to said exterior surface and said interior surface of the medical device, and wherein said first therapeutic agent is provided at a radially exterior surface with respect to the barrier layer and said second therapeutic agent is provided at a radially interior surface with respect to the barrier layer.

6. The method of claim 1, wherein a first subset of the openings are provided with a first barrier layer disposed near the interior surface of the medical device and said first therapeutic agent is provided at a radially exterior position with respect to the first barrier layer and a second subset of openings are provided with a second barrier layer disposed near the exterior surface of the medical device and said second therapeutic agent is provided at a radially interior position with respect to the second barrier layer.

27. The method of claim 1, wherein the first therapeutic agent is selected from the group consisting of an angiogenic agent and an antiproliferative agent.

28. The method of claim 27, wherein the second agent is selected from the group consisting of an antithrombotic agent, an antiplatelet agent, a vasodilator, and an anti-inflammatory agent.

7. A method of delivering two or more therapeutic agents, to a blood vessel comprising the steps of:

a) providing a substantially cylindrical medical device having an exterior surface, an interior surface, and openings traversing said exterior surface and said interior surface, said openings having a barrier layer arranged at a radially intermediate surface with respect to said exterior surface and said interior surface, wherein at least one first therapeutic agent is disposed in a therapeutic layer disposed at a radially exterior surface with respect to said barrier layer and wherein at least one second therapeutic agent is disposed in a therapeutic layer disposed at a radially interior surface with respect to said barrier layer;

b) delivering the medical device with the therapeutic agents to a lumen of a blood vessel; and

c) releasing the therapeutic agents over a time period sufficient to produce a therapeutic effect, wherein the first therapeutic agent is released substantially toward said exterior surface of the medical device and wherein the second therapeutic agent is released substantially toward said interior surface of the medical device.

8. The method of claim 7, wherein the first and second therapeutic agents are selected from the group consisting of:

a) different therapeutic agents;

b) different concentrations of therapeutic agents;

c) different release profiles of therapeutic agents; and

d) combinations of a)-c).

9. The method of claim 7, wherein the first therapeutic agent is selected from the group consisting of:

a) an antiproliferative agent;

b) an antiangiogenic agent;

c) an angiogenic agent;

d) an antirestenotic agent;

e) anti-inflammatory; and

f) combinations of a)-e).

10. The method of claim 9, wherein the second therapeutic agent is selected from the group consisting of:

a) an antithrombotic agent;

b) an antiplatelet agent;

c) a vasodilator;

d) anti-inflammatory; and

e) combinations of a)-d).

11. A method of delivering therapeutic agents to a blood vessel comprising the steps of:

a) providing a medical device comprising a first surface, a second surface, and openings traversing said first surface and said second surface, said openings containing therapeutic agents;

b) delivering the medical device with the therapeutic agents to a lumen of a blood vessel; and

c) releasing a first of the therapeutic agents to a wall of the blood vessel over a time period sufficient to produce a therapeutic effect; and

d) releasing a second of the therapeutic agents to the lumen of the blood vessel over a time period sufficient to produce a therapeutic effect.

12. The method of claim 11, wherein the first and second therapeutic agents are selected from the group consisting of:

a) different therapeutic agents;

b) different concentrations of therapeutic agents;

c) different release profiles of therapeutic agents; and

d) combinations of a)-c).

13. The method of claim 11, wherein the first therapeutic agent is selected from the group consisting of:

a) an antiproliferative agent;

b) an antiangiogenic agent;

c) an angiogenic agent;

d) an antirestenotic agent;

e) anti-inflammatory; and

f) combinations of a)-e).

14. The method of claim 13, wherein the second therapeutic agent is selected from the group consisting of:

a) an antithrombotic agent;

b) an antiplatelet agent;

c) a vasodilator;

d) anti-inflammatory; and

e) combinations of a)-d).

15. The method of claim 11, wherein the openings are provided with a barrier layer disposed at a radially intermediate location with respect to said first surface and said second surface of the medical device, and wherein said first therapeutic agent is provided at a radially exterior surface with respect to the barrier layer and said second therapeutic agent is provided at a radially interior surface with respect to the barrier layer.

16. The method of claim 11, wherein a first subset of the openings are provided with a first barrier layer disposed near the interior surface of the medical device and said first therapeutic agent is provided at a radially exterior position with respect to the first barrier layer and a second subset of openings are provided with a second barrier layer disposed near the exterior surface of the medical device and said second therapeutic agent is provided at a radially interior position with respect to the second barrier layer.

17. A drug delivery device comprising:

a medical device having an exterior surface and an interior surface;

a plurality of openings in the device body; and

a first therapeutic agent and a second therapeutic agent disposed in the openings and arranged to deliver the first therapeutic agent primarily to the exterior surface and to deliver the second therapeutic agent primarily to the interior surface.

18. The device of claim 17, wherein the openings in the medical device are through openings traversing the exterior surface and the interior surface.

19. The device of claim 17, wherein the first and second therapeutic agents selected from the group consisting of:

a) different therapeutic agents;

b) different concentrations of therapeutic agents;

c) different release profiles of therapeutic agents;

d) anti-inflammatory; and

e) combinations of a)-d).

20. The device of claim 17, wherein the first therapeutic agent is selected from the group consisting of an angiogenic agent an anti-inflammatory agent, and an antiproliferative agent.

21. The device of claim 20, wherein the second therapeutic agent is selected from the group consisting of an antirestenotic agent, an antithrombotic agent, an antiplatelet agent, an anti-inflammatory agent, and a vasodilator.

22. The device of claim 17, wherein the openings are provided with a barrier layer disposed at a radially intermediate position with respect to said exterior surface and said interior surface of the medical device, and wherein said first therapeutic agent is provided at a radially exterior position with respect to the barrier layer and said second therapeutic agent is provided at a radially interior position with respect to the barrier layer.

23. The device of claim 17, wherein a first subset of the openings are provided with a first barrier layer disposed near the interior surface of the medical device and said first therapeutic agent is provided at a radially exterior position with respect to the first barrier layer and a second subset of openings are provided with a second barrier layer disposed near the exterior surface of the medical device and said second therapeutic agent is provided at a radially interior position with respect to the second barrier layer.

29. The device of claim 18, wherein the through openings have a substantially uniform cross section between the interior and exterior surfaces.

30. The device of claim 22, wherein the barrier layer is bioerodible.

31. The device of claim 30, wherein the barrier layer has a predetermined erosion time which is longer than erosion times of biodegradable matrices containing the first and second therapeutic agents.

32. The device of claim 17, wherein the first therapeutic agent is contained within a biodegradable matrix and the first therapeutic agent has a concentration variation within the matrix.

33. The device of claim 17, wherein the second therapeutic agent is contained within a biodegradable matrix and the second therapeutic agent has a concentration variation within the matrix.

34. The device of claim 17, wherein the openings are substantially non-deforming openings.

24. A drug delivery device comprising:

an exterior surface;

an interior surface;

a plurality of openings traversing said exterior surface and said interior surface, said openings having a barrier layer arranged at a radially intermediate position with respect to said exterior surface and said interior surface;

at least one first therapeutic agent in a therapeutic layer disposed at a radially exterior position with respect to said barrier layer; and

and at least one second therapeutic agent in a therapeutic layer disposed at a radially interior position with respect to said barrier layer.

25. The device of claim 24, wherein the first therapeutic agent is selected from the group consisting of an angiogenic agent, an anti-inflammatory agent, and an antiproliferative agent.

26. The device of claim 25, wherein the second therapeutic agent is selected from the group consisting of an antirestenotic agent, an antithrombotic agent, an antiplatelet agent, an anti-inflammatory agent, and a vasodilator.

35. The device of claim 24, wherein the openings are substantially non-deforming openings.

36. The device of claim 24, wherein the barrier layer substantially prevents passage of the first and second therapeutic agents there through.

37. The device of claim 24, wherein the barrier layer is bioerodible.

38. The device of claim 37, wherein the barrier has a predetermined erosion time which is longer than erosion times of biodegradable matrices containing the first and second therapeutic agents.