Method of applying drug-release coatings

• US 5,980,972 A
• Filed: 09/22/1997
• Issued: 11/09/1999
• Est. Priority Date: 12/20/1996
• Status: Expired due to Term

• Current Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Original Assignee: Schneider Electric SE
• Inventors: Ding, Ni
• Primary Examiner(s): DUDASH, DIANA L
• Application Number:
  US08/935,371
• Time in Patent Office: 778 Days
• Field of Search: 427/2.24, 427/426, 427/430.1, 427/245, 427/246, 427/336, 427/2.28
• 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 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• 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
• 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: B05B 13/0442 Installation or apparatus for applying liquid or other fluent material to separate articles rotated during spraying operation
• CPC Class Codes: C08L 23/00 Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 31/04 Homopolymers or copolymers of vinyl acetate
• CPC Class Codes: C08L 75/04 Polyurethanes
• CPC Class Codes: C08L 77/00 Compositions of polyamides obtained by reactions forming a carboxylic amide link in the main chain of polyhydrazides C08L79/06; of polyamideimides or polyamide acids C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 83/04 Polysiloxanes

Abstract

The invention is directed to a method of applying drug-release coatings whereby a polymer can be dissolved in a first solvent (solvent A) to form a polymer system and a drug can be dissolved or suspended in a second solvent (solvent B) to form a drug system. The coating or layer of coating so formed comprises a substantially uniform combination of the drug and polymer. Solvent B can be the same as or different than solvent A. The coating can be applied on a stent body by separately spraying or dipping the polymer system and the drug system onto the devices. The coating can be accomplished by either applying the polymer and drug systems sequentially or simultaneously. In certain embodiments, a drug can be suspended in solvent B. In some cases, three or more systems can be utilized. For instance, a third system containing pure solvent A or B can smooth the coating surface, if the solvent of the third spraying system is compatible with the polymer matrix.

Claims

1. A method of making a medical device having at least a portion for insertion or implantation into the body of a patient, wherein the portion has a surface which is adapted for exposure to body tissue of the patient and wherein at least a part of the surface is covered with a coating comprising at least one layer, to release at least one biologically active material therefrom, the method comprising:

a) applying a thermodynamically stable polymer system substantially free of a biologically active material comprising a polymer and a first solvent of the polymer to the surface, and

b) applying a drug system substantially free of any polymer comprising a biologically active material and a second solvent of the biologically active material to the surface;

wherein said method forms a substantially homogenous composite layer of the polymer and the biologically active material.

2. The method of claim 1 wherein steps (a) and (b) are repeated.

3. The method of claim 1 wherein the medical device is a stent.

4. The method of claim 1 wherein the stent is a self-expanding stent.

5. The method of claim 1 wherein the first solvent and second solvent are the same.

6. The method of claim 1 wherein the first solvent and second solvent are different.

7. The method of claim 1 wherein the polymer is a hydrophobic biostable elastomer.

8. The method of claim 7, wherein the elastomer is selected from the group consisting of silicones, polyurethanes, thermoplastic elastomers, ethylene vinyl acetate copolymers, polyolefin elastomers, EPDM rubbers and polyamide elastomers.

9. The method of claim 1 wherein the biologically active material is selected from the group consisting of antithrobotics, anticoagulants, antiplatelet agents, thrombolytics, antiproliferatives, anti-inflammatories, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factors, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters and drugs that enhance the formation of healthy neointimal tissue.

10. The method of claim 1 wherein the polymer system or drug system is applied by spray coating.

11. The method of claim 1 wherein the polymer system or drug system is applied by dipping.

12. The method of claim 1 wherein the polymer system and the drug system are applied simultaneously to the surface.

13. The method of claim 1 wherein the polymer system and the drug system are applied sequentially to the surface.

14. The method of claim 1 which further comprises partially evaporating the first solvent prior to applying the drug system.

15. The method of claim 1 wherein the biologically active material is dissolved in the second solvent.

16. The method of claim 1 wherein the biologically active material is suspended in the second solvent.

17. The method of claim 1 which further comprises applying a solvent system to the coating layer.

18. The method of claim 1 which further comprises applying a second drug system substantially free of a polymer comprising a second biologically active material to the surface.