Drug release stent coating

• US 6,358,556 B1
• Filed: 01/23/1998
• Issued: 03/19/2002
• Est. Priority Date: 04/19/1995
• Status: Expired due to Term

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Corporation
• Inventors: Helmus, Michael N., Ding, Ni
• Primary Examiner(s): Beck, Shrive P.
• Assistant Examiner(s): Michener, Jennifer Kolb
• Application Number:
  US09/012,443
• Time in Patent Office: 1,516 Days
• Field of Search: 623/1, 623/2, 623/11, 623/12, 424/422, 424/423, 424/424, 427/2.1, 427/2.24, 427/2.25, 427/2.28, 427/2.3, 427/2.31, 427/488, 427/496, 427/533, 427/535, 427/551
• US Class Current: 427/2.24
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2/86 Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2210/0014 using shape memory or superelastic materials, e.g. nitinol
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/141 Plasticizers
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: C08L 5/00 Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides
• CPC Class Codes: C08L 75/04 : Polyurethanes
• CPC Class Codes: C08L 83/00 : Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 83/04 : Polysiloxanes
• CPC Class Codes: C08L 83/08 : containing silicon bound to organic groups containing atoms other than carbon, hydrogen and oxygen

Abstract

A method of coating implantable open lattice metallic stent prosthesis is disclosed which includes sequentially applying a plurality of relatively thin outer layers of a coating composition comprising a solvent mixture of uncured polymeric silicone material and crosslinker and finely divided biologically active species, possibly of controlled average particle size, to form a coating on each stent surface. The coatings are cured in situ and the coated, cured prosthesis are sterilized in a step that includes preferred pretreatment with argon gas plasma and exposure to gamma radiation electron beam, ethylene oxide, steam.

Claims

1. A process for making an implantable medical prosthesis in which at least a portion of the prosthesis is covered with a coating, wherein the process comprises:

(a) applying a composition, comprising a polymeric material incorporating a biologically active material, to the portion of the prosthesis to form a coating thereon;

(b) curing the coating;

(c) exposing the portion of the prosthesis to an inert gas plasma treatment after the coating is cured; and

(d) sterilizing the portion of the prosthesis with gamma radiation.

2. The process of claim 1 wherein the inert gas is selected from the group consisting of argon, helium or mixtures thereof.

3. The process of claim 2 wherein the inert gas is argon.

4. The process of claim 1 wherein the portion of the prosthesis is exposed to the inert gas plasma treatment for about 30 seconds to about 5 minutes.

5. The process of claim 4 wherein the portion of the prosthesis is exposed to the inert gas for an additional period of time.

6. The process of claim 5 wherein the additional period of time is about 5 minutes.

7. The process of claim 1 wherein the gamma radiation is about 2.5 to about 3.5 Mrad.

8. The process of claim 1 wherein the coating is cured by a method selected from the group consisting of applying a heat source to the coating and applying a chemical agent to the coating.

9. The process of claim 1 wherein the biologically active material has an average particle size of equal to or less than about 15 μ

m.

10. The process of claim 9 wherein the biologically active material has an average particle size of equal to or less than about 10 μ

m.

11. The process of claim 9 wherein the coating reduces an initial burst release of the biologically active material upon implantation of the prosthesis as compared to a coating comprising the same biologically active material having an average particle size greater than about 15 μ

m.

12. The process of claim 1 wherein the composition comprises about 25-45 weight percent of the biologically active material.

13. The process of claim 1 wherein the biologically active material includes heparin.

14. The process of claim 1 wherein the polymeric material is a hydrophobic elastomeric material.

15. The process of claim 14 wherein the hydrophobic elastomeric material is selected from the group consisting of silicones, polyurethanes, polyamide elastomers, ethylene vinyl acetate copolymers, polyolefin elastomers, ethylene-propylene terpolymer rubbers and combinations thereof.

16. The process of claim 14 wherein the prosthesis is an expandable stent having a tubular metal body having open ends and a sidewall structure having openings therein and wherein the composition is applied to the stent in a manner such that the composition adheringly conforms to the sidewall structure to preserve the openings therein when the stent is expanded.

17. An implantable medical prosthesis prepared according to the process of claim 1.

18. The process of claim 1 Wherein the prosthesis is an expandable stent.

19. The process of claim 18 wherein the expandable stent is self-expanding.

20. A process for making an expandable stent in which at least a portion of the stent is covered with a coating, wherein the process comprises:

(a) applying a composition, comprising a hydrophobic elastomeric material incorporating a biologically active material, to the portion of the stent to form a coating thereon;

(b) curing the coating;

(c) exposing the portion of the stent to an argon plasma treatment after the coating is cured; and

(d) sterilizing the portion of the stent with gamma radiation.

21. A process for making an expandable stent in which at least a portion of the stent is covered with a coating, wherein the process comprises:

(a) applying a composition, comprising a polymeric material incorporating a biologically active material, to the portion of the stent to form a coating thereon;

(b) curing the coating;

(c) exposing the portion of the stent to an argon plasma treatment for about 30 seconds to about 5 minutes after the coating is cured; and

(d) sterilizing the portion of the stent with gamma radiation of about 2.5 to about 3.4 Mrad.