Post-processing of a medical device to control morphology and mechanical properties

• US 9,956,385 B2
• Filed: 06/25/2013
• Issued: 05/01/2018
• Est. Priority Date: 06/28/2012
• Status: Active Grant

• Current Assignee: Spectranetics Corporation (Koninklijke Philips N.V.)
• Original Assignee: Spectranetics Corporation (Koninklijke Philips N.V.)
• Inventors: Ruane, Patrick H.
• Primary Examiner(s): Yuan, Dah-Wei D
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US13/926,515
• Publication Number:
  US 20140004253A1
• Time in Patent Office: 1,771 Days
• Field of Search: 623 111, 427 225
• CPC Class Codes: A61L 2/00 Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for contact lenses A61L12/00; atomisers for disinfecting agents A61M; sterilisation of packages or package contents in association with packaging B65B55/00; treatment of water, waste water, sewage or sludge C02F; disinfecting paper D21H21/36; disinfecting devices for water closets E03D; articles having provision for disinfection, see the relevant subclasses for these articles, e.g. H04R1/12
• CPC Class Codes: A61L 2/206 Ethylene oxide
• CPC Class Codes: A61L 2202/24 Medical instruments, e.g. endoscopes, catheters, sharps
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 25/1029 Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B05D 1/18 performed by dipping
• CPC Class Codes: B05D 3/107 Post-treatment of applied coatings
• CPC Class Codes: C09D 171/02 Polyalkylene oxides

Abstract

A method of forming a coated medical device is described in which a coating including a therapeutic agent dispersed in a polymer or oligomer matrix is applied to an outer surface of the medical device. The coating is then post-processed to selectively remove a substantial portion of the polymer or oligomer matrix from the coating. The post-processed coating is then sterilized.

Claims

1. A method of forming a coated medical device comprising:

applying a coating to an outer surface of a medical device, the coating including a therapeutic agent dispersed in a matrix of a polymer or oligomer excipient;

post-processing the medical device by immersion in a solvent or solution, thereby selectively removing a substantial portion of the polymer or oligomer excipient from the matrix in which the therapeutic agent is dispersed; and

sterilizing the post-processed medical device,

wherein the coating comprises less than 50% by weight of the therapeutic agent prior to post-processing, and the coating comprises greater than 50% by weight of the therapeutic agent after post-processing.

2. The method of claim 1, wherein the therapeutic agent is substantially water insoluble.

3. The method of claim 2, wherein the coating comprises 35% or less by weight of the therapeutic agent prior to post-processing, and the coating comprises 65% or more by weight of the therapeutic agent after post-processing.

4. The method of claim 2, wherein less than 10% by weight of the therapeutic agent is removed from the coating during post-processing.

5. The method of claim 4, wherein greater than 75% by weight of the polymer or oligomer excipient is removed from the coating during post-processing.

6. The method of claim 2, wherein less than 15% by weight of therapeutic agent is removed from the coating during post-processing.

7. The method of claim 6, wherein greater than 90% of the polymer or oligomer excipient is removed from the coating during post-processing.

8. The method of claim 2, wherein the substantially water insoluble therapeutic agent comprises a taxane.

9. The method of claim 8, wherein the taxane is selected from the group consisting of pactlitaxel, paclitaxel analogues, and paclitaxel derivatives thereof.

10. The method of claim 1, wherein applying the coating comprises dip coating an expandable portion of the medical device in a solution comprising:

paclitaxel;

iodine;

a polymer; and

solvent.

11. The method of claim 10, wherein the polymer is soluble in both water, and a solvent solution comprising an organic solvent and less than 20% by weight water.

12. The method of claim 10, wherein the polymer has a molecular weight below 20,000 Daltons.

13. The method of claim 12, wherein the polymer is polyethylene glycol (PEG).

14. The method of claim 13, wherein the solvent comprises a mixture of ethanol and acetonitrile.

15. The method of claim 2, wherein post-processing the medical device comprises immersing the medical device in an aqueous solution.

16. The method of claim 15, wherein immersing the medical device in the aqueous solution comprises immersing the medical device in the aqueous solution for 5 minutes or less.

17. The method of claim 15, wherein immersing the medical device in the aqueous solution comprises immersing the medical device in the aqueous solution for 1 minute or less.

18. The method of claim 2, wherein post-processing the medical device comprises immersing the medical device in a solution comprising an organic solvent.

19. The method of claim 18, wherein the solution further comprises water.

20. The method of claim 2, wherein sterilizing the post-processed medical device comprises exposing the medical device to a relative humidity.

21. The method of claim 20, wherein sterilizing comprises a pre-conditioning stage, a sterilization stage, and an aeration stage.