Lipid coating for medical devices delivering bioactive agent

• US 8,927,000 B2
• Filed: 06/30/2011
• Issued: 01/06/2015
• Est. Priority Date: 06/30/2010
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Chappa, Ralph A., Meyering, Emily R. Rolfes
• Primary Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US13/173,143
• Publication Number:
  US 20120165786A1
• Time in Patent Office: 1,286 Days
• Field of Search: 424/422, 604/915, 604/103.02
• US Class Current: 424/422
• CPC Class Codes: A61L 29/044 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: C08L 91/00 Compositions of oils, fats or waxes; Compositions of derivatives thereof

Abstract

The present invention relates compositions for delivering therapeutic agents from a medical device including an expandable and collapsible structure and methods employing them. A lipid coating including one or more fatty acids increases the amount of therapeutic agent released from the device at the delivery site. The therapeutic agent can be in a matrix including a hydrophilic polymer or an amphiphilic polymer. Release and adhesion coatings can also facilitate delivery of therapeutic agent.

Claims

1. A medical device comprising:

a balloon,

a coating on all or a portion of the balloon, the coating comprising (i) nano- or microparticles that comprise a bioactive agent and (ii) a flexible hydrogel matrix, and

a lipid coating on the coating comprising the bioactive agent, the lipid coating having a melting or softening point greater than room temperature and less than body temperature of the subject and comprising a plurality of fatty acids;

the device being effective for delivering the bioactive agent to a site within a subject.

2. The device of claim 1, wherein the lipid coating comprises two fatty acids.

3. The device of claim 1, wherein the plurality of fatty acids is a mixture of fatty acids that are solid at room temperature and soft or liquid at body temperature of the subject.

4. The device of claim 1, wherein the plurality of fatty acids is a mixture of fatty acids that comprises oleic acid, dodecanoic acid, or salt thereof.

5. The device of claim 1, wherein the fatty acids comprise:

a saturated fatty acid of formula;

CH₃(CH₂)_nCOOH, where n is an integer in the range of 4 to 20; and

an unsaturated fatty acid of formula;

CH₃(CH₂)_mC═

C(CH₂)_oCOOH, where m and o are independently integer in the range of 2 to 20;

or

salts thereof.

6. The device of claim 1, wherein the balloon is an angioplasty balloon.

7. The device of claim 1, wherein the bioactive agent comprises an antiproliferative agent, an antiinflamatory agent, or an antiplatelet agent.

8. The device of claim 7, wherein the bioactive agent comprises paclitaxel.

9. The device of claim 1, wherein a majority of the nano- or microparticles are non-homogenously distributed in the flexible hydrogel matrix, and partially embedded in the flexible hydrogel matrix at its surface.

10. The device of claim 1, wherein the nano- or microparticles consist of the therapeutic agent.

11. The device of claim 1, wherein about 10% to 100% of the nano- or microparticles associated with the balloon or coating are released from the device upon expansion of the balloon.

12. The device of claim 1, wherein the coating comprising the flexible hydrogel matrix comprises a hydrogel polymer selected from the group consisting of poly(acrylamide), poly(methacrylamide), poly(vinylpyrrolidone), poly(acrylic acid), poly(ethylene glycol), poly(vinyl alcohol), poly(HEMA), methyl vinyl ether/maleic anhydride copolymers, vinyl pyrrolidone/(meth)acrylamide copolymers, and mixture thereof.

13. The device of claim 1, wherein the coating comprising the flexible hydrogel matrix comprises a polymer comprising pendent reacted photogroups that covalently bond the polymer to other polymers in the coating or to a surface of the expandable and collapsible structure.

14. The device of claim 1, wherein the coating comprising the bioactive agent has a thickness of about 5 μ

m to about 100 μ

m.

15. The device of claim 1, wherein the nano- or microparticles have an average greatest dimension of about 0.1 μ

m to about 10 μ

m.

16. A method of delivering a bioactive agent to a site in a subject, the method comprising:

providing the medical device of claim 1 at a site in a subject; and

expanding the balloon at the site in the subject to contact a tissue at the site with the coating comprising the bioactive agent and the lipid coating and to release bioactive agent to the tissue.

17. The device of claim 1, wherein the melting point is in the range of 25°

C. to 37°

C.