Implantable medical device with beneficial agent concentration gradient

• US 20060147489A1
• Filed: 03/07/2006
• Published: 07/06/2006
• Est. Priority Date: 03/28/2003
• Status: Active Grant

• Current Assignee: Innovational Holdings, LLC
• Original Assignee: Conor Medsystems Incorporated
• Inventors: Park, Kinam, Shanley, John F., Parker, Theodore L.
• Granted Patent: US 8,449,901 B2
• Time in Patent Office: Days
• US Class Current: 424/425
• CPC Class Codes: A61L 2300/60 characterised by a special physical form
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

The implantable medical devices are configured to release at least one therapeutic agent from a matrix affixed to the implantable body with a release profile which is programmable to the agent and treatment. The matrix is formed such that the concentration of the therapeutic agent in the matrix varies as a gradient relative to a surface of the implantable body. The change in the concentration gradient of the agent in the matrix directly controls the rate of elution of the agent from the matrix. The therapeutic agent matrix can be disposed in the stent or on surfaces of the stent in various configurations, including within volumes defined by the stent, such as openings, holes, or concave surfaces, as a reservoir of agent, and alternatively as a coating on all or a portion of the surfaces of the stent structure.

Claims

1. An implantable medical device configured to release at least one therapeutic agent therefrom, the device comprising:

an implantable body; and

a matrix affixed to the implantable body, the matrix containing the at least one therapeutic agent therein, wherein the matrix is formed such that the concentration of the therapeutic agent in the matrix varies as a gradient relative to a surface of the matrix with a high concentration of the therapeutic agent spaced a distance from the matrix surface and a low concentration of the therapeutic agent at the matrix surface.

2. The device of claim 1, wherein the matrix comprises a bioresorbable polymer.

3. The device of claim 1, wherein the implantable body is substantially cylindrical.

4. The device of claim 3, wherein the matrix is disposed in an opening in a mural surface of the implantable body.

5. The device of claim 3, wherein the matrix is disposed in an opening in a luminal surface of the implantable body.

6. The device of claim 3, wherein the concentration gradient of the therapeutic agent in the matrix increases from a minimum concentration of therapeutic agent at a luminal surface of the implantable body, reaches a maximum concentration of therapeutic agent in a center portion of the expandable body and then decreases towards a mural surface of the implantable body.

7. The device of claim 3, wherein the concentration of the therapeutic agent in the matrix is higher at a mural surface of the implantable body than at a luminal surface of the implantable body.

8. The device of claim 3, wherein the concentration of the therapeutic agent in the matrix is higher at a luminal surface of the implantable body than at a mural surface of the implantable body.

9. The device of claim 1, wherein the matrix is disposed in an opening passing through the implantable body.

10. The device of claim 1, wherein the matrix is disposed as a coating on the surface of the implantable body.

11. The device of claim 1, wherein the therapeutic agent is dissolved in the matrix in a solid solution morphology.

12. The device of claim 11, wherein the therapeutic agent is dispersed in the matrix in a solid emulsion morphology.

13. The device of claim 1, wherein the therapeutic agent elutes from the matrix at a rate that is controlled by the concentration gradient of the therapeutic agent in the matrix.

14. The device of claim 1, wherein the at least one therapeutic agent comprises a plurality of therapeutic agents.

15. The device of claim 14, wherein the concentration of each of the therapeutic agents in the matrix vary with different continuous concentration gradients relative to the surface of the implantable body.

16. The device of claim 1, wherein the therapeutic agent is selected from the group consisting of antithrombotic agents, antiproliferative agents, and antirestenotic agents.

17. The device of claim 1, wherein the matrix is selected from the group consisting of poly(lactide-co-glycolide) (PLGA) and Poly vinylpyrrolidone (PVP).

18. The device of claim 1, wherein the implantable body is substantially cylindrical, the matrix is disposed in a plurality of holes passing through the implantable body, and the matrix is separated from a luminal side of the implantable body by a barrier layer.

19. The device of claim 18, wherein the therapeutic agent has a maximum concentration substantially adjacent to the barrier layer and a minimum concentration substantially adjacent to a mural surface of the implantable body.

20. The device of claim 18, wherein the implantable body is substantially cylindrical and the holes are radial directed holes formed in a plurality of struts of the implantable body.

21. The device of claim 1, wherein the implantable medical device is a stent.

22. The device of claim 1, wherein the matrix is affixed to the stent by placing the matrix in a recess in the stent.