Medical device coatings for releasing a therapeutic agent at multiple rates

• US 8,932,345 B2
• Filed: 02/04/2008
• Issued: 01/13/2015
• 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: Moore, William F., Shirley, Gary Bradford
• Primary Examiner(s): Isabella, David
• Assistant Examiner(s): Woznicki, Jacqueline
• Application Number:
  US12/025,495
• Publication Number:
  US 20080195079A1
• Time in Patent Office: 2,535 Days
• Field of Search: 623 11- 154, 623/96.01, 427 224- 225, 427/2.28, 427/2.3, 604/96.01
• US Class Current: 623/1.46
• 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. An implantable medical device having a coating on an abluminal surface extending from a proximal end to a distal end, the coating formed by the steps of:

spraying droplets having a first average liquid droplet size and comprising a solution of a volatile solvent and a taxane therapeutic agent onto a first region of the abluminal surface;

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

spraying droplets having a second average liquid droplet size and comprising the solution of the volatile solvent and the taxane therapeutic agent onto a second region of the abluminal surface;

wherein the second average liquid droplet size is greater than the first average liquid droplet size; and

evaporating the volatile solvent to form a coating of the taxane therapeutic agent on the second region, wherein release of the taxane therapeutic agent from the first region in an aqueous medium is faster than release of the taxane therapeutic agent from the second region in the aqueous medium, and

wherein the coating consists essentially of the taxane therapeutic agent and an antithrombotic agent on the first region and on the second region and does not include a polymer.

2. The coated implantable medical device of claim 1, where the coating consists essentially of a particulate coating on the abluminal surface comprising:

a. the first region including the plurality of first particles comprising the taxane therapeutic agent and having a first average diameter, the first region extending from the distal end to the second region; and

b. the second region including the plurality of second particles comprising the taxane therapeutic agent and having a second average diameter, the second region positioned proximal to the first region.

3. The coated medical device of claim 2, wherein the first average diameter and the second average diameter are both between about 1 to 100 micrometers.

4. The coated medical device of claim 2, wherein the second average diameter is at least 60% larger than the first average diameter.

5. The coated medical device of claim 2, wherein the first average diameter is between 1 and 20 micrometers and the second average diameter is between 30 and 50 micrometers.

6. The coated medical device of claim 2, wherein the taxane therapeutic agent in the first region elutes at least about 15% faster than the taxane therapeutic agent in the 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.

7. The coated medical device of claim 2, where the coating on the abluminal surface further comprises:

a third region including a plurality of third particles comprising the taxane therapeutic agent and having a third average diameter that is less than the second average diameter, the third region positioned between the distal end and the second region.

8. The coated medical device of claim 2, where the medical device is a catheter balloon, a radially expandable vascular support frame or the vascular support frame disposed around a balloon portion of the catheter balloon;

a. where the particulate coating on the abluminal surface of the medical device further comprises a third region including a plurality of third particles comprising the taxane therapeutic agent and having a third average diameter that is less than the second average diameter, the third region positioned between the distal end and the second region; and

where

i. the first region and the second region are contained within a continuous layer of the particulate coating;

ii. the particulate coating is a single-layer coating;

iii. the taxane therapeutic agent is paclitaxel;

iv. the first region elutes at a faster rate than the second region when contacted with an ethanol elution medium;

v. the first region comprises a first concentration of the paclitaxel that is greater than the concentration of the paclitaxel in the second region;

vi. the first region elutes at least about 15% faster than the 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;

vii. the first region comprises about 3-10 micrograms paclitaxel per mm² of the coated abluminal surface area of the first region, and the second region comprises about 0.1-2.0 micrograms of paclitaxel per mm² of the coated abluminal surface area of the second region;

viii. the first region and the second region contain particles with a first average diameter of the first particles and the second average diameter of the second particles both being between about 1 to 100 micrometers, with the first average diameter being between about 1 and 20 micrometers and the second average diameter being about 30 micrometers to about 50 micrometers; and

where the second average diameter is at least 60% larger than the first average diameter; and

ix. the coating is free of a polymer; and

where

b. the first region is formed by spraying the solution at a first atomization pressure and the second region is formed by spraying the solution at a second atomization pressure.

9. The coated medical device of claim 1, wherein the first region and the second region are contained within a continuous layer of the coating.

10. The coated medical device of claim 1, wherein the coating is a single-layer coating.

11. The coated medical device of claim 1, wherein the taxane therapeutic agent is paclitaxel.

12. The coated medical device of claim 1, wherein the first region comprises a first concentration of the taxane therapeutic agent and the second region comprises a second concentration of the taxane-therapeutic agent, wherein the first concentration is greater than the second concentration.

13. The coated medical device of claim 12, wherein the taxane therapeutic agent is paclitaxel and wherein the first region comprises about 3-10 micrograms of paclitaxel per mm² of the coated abluminal surface area of the first region, and the second region comprises about 0.1-2.0 micrograms of paclitaxel per mm² of the coated abluminal surface area of the second region.

14. The coated medical device of claim 1, wherein the implantable medical device is a balloon catheter having a balloon comprising the abluminal surface.

15. The coated medical device of claim 1, wherein the first region is coated by spraying the solution at a first atomization pressure and the second region is coated by spraying the solution at a second atomization pressure.

16. The coated medical device of claim 1, wherein the first region elutes at a faster rate than the 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.

17. The coated medical device of claim 1, wherein the coating of the taxane therapeutic agent on the first and second regions contains less than 0.1 microgram per mm² of a non-polymer carrier modifying a rate of release of the therapeutic agent.

18. The coated medical device of claim 1, wherein the coating of the taxane therapeutic agent on the first and second regions consists essentially of the taxane therapeutic agent.

19. The coated medical device of claim 1, wherein the droplets having a first average liquid droplet size and the droplets having a first average liquid droplet size consist essentially of a solution of the volatile solvent and the taxane therapeutic agent.

20. An implantable medical device having a coating on an abluminal surface extending from a proximal end to a distal end, the coating formed by the steps of:

spraying droplets having a first average liquid droplet size and comprising a solution of a volatile solvent and a taxane therapeutic agent onto a first region of the abluminal surface;

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

spraying droplets having a second average liquid droplet size and comprising the solution of the volatile solvent and the taxane therapeutic agent onto a second region of the abluminal surface;

wherein the second average liquid droplet size is greater than the first average liquid droplet size; and

evaporating the volatile solvent to form a coating of the taxane therapeutic agent on the second region, wherein release of the taxane therapeutic agent from the first region in an aqueous medium is faster than release of the taxane therapeutic agent from the second region in the aqueous medium,

wherein the coating of the taxane therapeutic agent on the first region and on the second region does not include a polymer; and

where the coating consists essentially of a particulate coating on the abluminal surface comprising;

a. the first region including the plurality of first particles comprising the taxane therapeutic agent and having a first average diameter, the first region extending from the distal end to the second region; and

b. the second region including the plurality of second particles comprising the taxane therapeutic agent and having a second average diameter, the second region positioned proximal to the first region; and

wherein the taxane therapeutic agent is paclitaxel and wherein the first region comprises about 3-10 micrograms of paclitaxel per mm² of the coated abluminal surface area of the first region, and the second region comprises about 0.1-2.0 micrograms of paclitaxel per mm² of the coated abluminal surface area of the second region.

21. An implantable medical device having a coating on an abluminal surface extending from a proximal end to a distal end, the coating formed by the steps of:

spraying droplets having a first average liquid droplet size and comprising a solution of a volatile solvent and a taxane therapeutic agent onto a first region of the abluminal surface;

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

spraying droplets having a second average liquid droplet size and comprising the solution of the volatile solvent and the taxane therapeutic agent onto a second region of the abluminal surface;

wherein the second average liquid droplet size is greater than the first average liquid droplet size; and

evaporating the volatile solvent to form a coating of the taxane therapeutic agent on the second region, wherein release of the taxane therapeutic agent from the first region in an aqueous medium is faster than release of the taxane therapeutic agent from the second region in the aqueous medium,

wherein the coating of the taxane therapeutic agent on the first region and on the second region does not include a polymer; and

where the coating consists essentially of a particulate coating on the abluminal surface comprising;

a. the first region including the plurality of first particles comprising the taxane therapeutic agent and having a first average diameter, the first region extending from the distal end to the second region; and

b. the second region including the plurality of second particles comprising the taxane therapeutic agent and having a second average diameter, the second region positioned proximal to the first region; and

wherein the first average diameter is between 1 and 20 micrometers and the second average diameter is between 30 and 50 micrometers.