Medical device coatings for releasing a therapeutic agent at multiple rates

• US 9,656,003 B2
• Filed: 12/09/2014
• Issued: 05/23/2017
• Est. Priority Date: 02/07/2007
• Status: Active Grant

• Current Assignee: Cook Medical Technologies, LLC (Cook Group Incorporated)
• Original Assignee: Cook Medical Technologies, LLC (Cook Group Incorporated)
• Inventors: Shirley, Gary Bradford, Moore, William F.
• Primary Examiner(s): SELLMAN, CACHET I
• Application Number:
  US14/564,604
• Publication Number:
  US 20150093496A1
• Time in Patent Office: 896 Days
• Field of Search: 427 224, 427 225, 427 228, 4274211, 623 142, 623 143
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2240/00 Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
• 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 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• 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

Medical device coatings are provided that simultaneously release a therapeutic agent at different rates from different portions of the medical device coating. In a first embodiment, medical device coatings are provided that include particles comprising a therapeutic agent with two or more different particles sizes within a single layer on a surface of the implantable device. In a second embodiment, medical device coatings are provided having a higher concentration of the therapeutic agent in a first region of the coating than in a second region of the coating. In a third embodiment, medical device coatings are provided that are formed by certain coating processes wherein the droplet size of a spray coating solution is changed during the coating process. These coating processes preferably include applying a solution comprising a therapeutic agent and a suitable solvent to a surface of an implantable medical device. In a fourth embodiment, methods of treatment are provided that include implanting a coated medical device.

Claims

1. A method of manufacturing a coated medical device comprising an implantable structure having a coated surface extending from a proximal end to a distal end, the method comprising:

spraying first droplets of a solution having a first average liquid droplet size onto a first region of the surface, wherein the solution comprises a first therapeutic agent dissolved in a volatile solvent;

evaporating the volatile solvent from the first region to form a coating of the first therapeutic agent on the first region;

spraying second droplets of the solution having a second average liquid droplet size onto a second region of the surface;

evaporating the volatile solvent from the second region to form a coating of the first therapeutic agent on the second region,

wherein the first average droplet size differs from the second average droplet size and wherein the first therapeutic agent elutes at a different rate from the first region than from the second region when the first and second regions are implanted in the vascular system of a subject.

2. The method of claim 1, where the coating of first therapeutic agent on the first region and on the second region consists essentially of the first therapeutic agent.

3. The method of claim 1, wherein the coating of first therapeutic agent on the first region and on the second region does not include a polymer.

4. The method of claim 1, wherein the first therapeutic agent is a taxane.

5. The method of claim 4, wherein the taxane is paclitaxel.

6. The method of claim 1, wherein the implantable structure is a stent.

7. The method of claim 1, wherein the implantable structure is a balloon.

8. The method of claim 1, wherein the first droplets and the second droplets further comprise an antithrombotic agent.

9. The method of claim 8, wherein the first therapeutic agent is paclitaxel.

10. The method of claim 1, wherein the first region is coated by spraying the droplets at a first atomization pressure and the second region is coated by spraying the droplets at a second atomization pressure, and wherein the first atomization pressure differs from the second atomization pressure.

11. The method of claim 1, wherein at least one of the first region and the second region is coated with 3-10 microgram of the first therapeutic agent per mm² of the coated surface area, and wherein the first therapeutic agent is paclitaxel.

12. The method of claim 1, wherein first therapeutic agent on the first coating region elutes at least about 15% faster than the first therapeutic agent on second region when contacted with a porcine serum elution medium prepared by adding 0.104 mL of a 6.0 g/L heparin solution to porcine serum at 37°

C. and adjusting the pH to 5.6+/−

0.3 using a 20% v/v aqueous solution of acetic acid.

13. The method of claim 1, further comprising spraying third droplets of the solution having a third average liquid droplet size onto a third region of the surface;

evaporating the volatile solvent from the third region to form a coating of the first therapeutic agent on the third region,

wherein the third average droplet size differs from the first average droplet size and the second average droplet size.

14. The method of claim 1, wherein the coating on the first region and the second region form a continuous coating.

15. The method of claim 1, wherein the coating on the first region and on the second region form an outermost coating on the implantable structure.

16. The method of claim 1, wherein the coating of first therapeutic agent on the first region and on the second region comprises less than 0.1 microgram/mm² of materials other than the first therapeutic agent.

19. The method of claim 9, wherein the coating on the first region and on the second region forms an outermost coating on the implantable structure.

17. A method of manufacturing a coated medical device having an implantable structure having an abluminal surface extending from a proximal end to a distal end, the method comprising:

spraying first droplets of a solution having a first average liquid droplet size onto a first region of the abluminal surface, wherein the solution comprises paclitaxel dissolved in a volatile solvent;

evaporating the volatile solvent from the first region to form a coating of the paclitaxel on the first region;

spraying second droplets of the solution having a second average liquid droplet size onto a second region of the abluminal surface;

evaporating the volatile solvent from the second region to form a coating of the paclitaxel on the second region,

wherein the first average droplet size differs from the second average droplet size, wherein the implantable structure is selected from the group consisting of a stent and a balloon and wherein the paclitaxel on the first coating region elutes at least about 15% faster than the paclitaxel on second region when contacted with a porcine serum elution medium prepared by adding 0.104 mL of a 6.0 g/L heparin solution to porcine serum at 37°

C. and adjusting the pH to 5.6+/−

0.3 using a 20% v/v aqueous solution of acetic acid.

18. The method of claim 17, wherein the coating of paclitaxel on the first region and on than second region comprises less than 0.1 microgram/mm2 of materials other than paclitaxel.

20. A method of manufacturing a coated medical device comprising an implantable structure having a coated surface extending from a proximal end to a distal end, the method comprising:

spraying first droplets having a first average liquid droplet size onto a first region of the surface, wherein the first droplets comprise a first therapeutic agent dissolved in a first volatile solvent;

evaporating the first volatile solvent from the first region to form a coating of the first therapeutic agent on the first region;

spraying second droplets having a second average liquid droplet size onto a second region of the surface, wherein the second droplets comprise the first therapeutic agent dissolved in a second volatile solvent;

evaporating the second volatile solvent from the second region to form a coating of the first therapeutic agent on the second region,

wherein the first average droplet size differs from the second average droplet size,

wherein the first therapeutic agent elutes at a different rate from the first region than from the second region when the first and second regions are implanted in the vascular system of a subject and wherein the coating of first therapeutic agent on the first region and on the second region comprises less than 0.1 microgram/mm² of materials other than the first therapeutic agent.