Method and system for irradiation of a drug eluting implantable medical device

• US 7,887,871 B2
• Filed: 08/28/2008
• Issued: 02/15/2011
• Est. Priority Date: 07/31/2003
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Dehnad, Houdin
• Primary Examiner(s): Barr; Michael
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US12/200,725
• Publication Number:
  US 20080317939A1
• Time in Patent Office: 901 Days
• Field of Search: 427/2.21, 427/2.15, 427/2.24, 427/2.1, 600/30, 428/457, 438/633, 512/93, 128/899
• US Class Current: 427/2.1
• CPC Class Codes: B05D 1/002 the substrate being rotated
• CPC Class Codes: B05D 1/02 performed by spraying
• CPC Class Codes: B05D 3/0254 After-treatment
• CPC Class Codes: B05D 3/06 by exposure to radiation B05D3/02 takes precedence ; plasma treatment B05D3/141
• CPC Class Codes: B05D 3/068 using ionising radiations (gamma, X, electrons)
• CPC Class Codes: B05D 3/14 by electrical means
• CPC Class Codes: Y10T 428/31678 Of metal

Abstract

A method and system for modifying a drug delivery polymeric substrate for an implantable device, such as a stent, is disclosed.

Claims

1. A method of manufacturing a drug delivery implantable medical device, comprising exposing a coating of the device to charged particles for a duration, the coating comprising a polymer and an active agent;

wherein the coating comprises a barrier layer disposed over a layer comprising the polymer and the active agent; and

wherein the charged particles create tracks that only penetrate through the barrier layer and stop at an upper surface of the layer comprising the polymer and the active agent.

2. The method of claim 1, wherein exposing the coating of the device to charged particles comprises directing a beam of charged particles to the coating and directing another beam of different charged particles to the coating.

3. The method of claim 2, wherein the beams are directed to the coating simultaneously.

4. The method of claim 2, wherein the beams are directed to the coating sequentially.

5. The method of claim 1, wherein exposing the coating of the device to charged particles comprises directing a beam of the charged particles to the coating at an angle of about 20°

to the coating surface.

6. The method of claim 1, wherein the coating is exposed to the charged particles in a chamber having a chamber pressure less than atmospheric pressure.

7. The method of claim 1, wherein the coating comprises less than about 2% residual fluid content (w/w) when exposed to the charged particles.

8. The method of claim 1, wherein parameters of the method are selected such that permeability of the polymer to the active agent is changed in vivo as compared to if the coating was not exposed to charged particles under the same parameters.

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

10. The method of claim 1, further comprising exposing the coating to a fluid, subsequent to exposing the coating of the device to the charged particles, to remove fragments from the coating.

11. The method of claim 10, wherein the fluid includes an etchant selected from the group consisting of HNO₃, NaOH, KOH, HCl, Na₂CO₃, CrO₃, H₂SO₄, KMnO₄, NaOCl, and Na₂B₄O₇.

12. The method of claim 10, wherein the fluid is an organic solvent.

13. The method of claim 1, further comprising exposing the coating to a gas while exposing the coating to the charged particles.

14. The method of claim 13, wherein the gas is selected from the group consisting of hydrogen, SO₂ and oxygen.

15. The method of claim 1, wherein the barrier layer comprises a second polymer which may be the same as or different from the polymer of the layer comprising the polymer and the active agent, the second polymer comprising a percent crystallinity of about 50% or more before exposure to the charged particles.

16. The method of claim 1, wherein the parameters of exposure are sufficient to increase the release rate of the active agent in a patient by 10% to 25% as compared to if the coating were not subjected to charged particles.

17. The method of claim 1, further comprising masking a part of the coating such that an outer surface of the coating under the mask is protected from the exposure to the charged particles.

18. The method of claim 1, wherein the charged particles are not gamma radiation, electron beam, or plasma.

19. The method of claim 1, wherein the energy of the charged particles is 20 eV to 15 MeV.

20. The method of claim 1, wherein exposing the coating of the device to charged particles comprises directing a beam of the charged particles to the coating at an angle of 90°

to the coating surface.

21. The method of claim 1, wherein exposing the coating of the device to charged particles comprises directing a beam of the charged particles to the coating at an angle of about 20°

to about 80°

to the coating surface.

22. The method of claim 1, wherein the charged particles are selected from the group consisting of helium, oxygen, argon, fluorine, titanium, nitrogen, antimony, uranium, krypton, xenon, gold, neon, and combinations thereof.

23. The method of claim 19, wherein the current density of the charged particles is 0.001 μ

A/cm² to 1 μ

A/cm².

24. The method of claim 1, wherein the duration of the exposure is not longer than 1 hour.

25. The method of claim 1, wherein the ion fluence of the charged particles is 10³/cm² to 10¹⁶/cm².

26. The method of claim 1, wherein exposing the coating of the device to charged particles comprises directing a beam of the charged particles to the coating at an angle of about 20°

to about 40°

to the coating surface.