Methods for forming stent coatings comprising hydrophilic additives

• US 9,175,162 B2
• Filed: 09/19/2007
• Issued: 11/03/2015
• Est. Priority Date: 05/08/2003
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Pacetti, Stephen D., Tang, Yiwen
• Primary Examiner(s): Switzer, Juliet
• Assistant Examiner(s): HELM, CARALYNNE E
• Application Number:
  US11/903,011
• Publication Number:
  US 20080021008A1
• Time in Patent Office: 2,967 Days
• Field of Search: 424/422, 623/1.42
• US Class Current: 1/1
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08L 2666/04 Macromolecular compounds according to groups C08L7/00 - C08L49/00, or C08L55/00 - C08L57/00; Derivatives thereof
• CPC Class Codes: C08L 2666/22 Macromolecular compounds not provided for in C08L2666/16 - C08L2666/20
• CPC Class Codes: C08L 33/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C08L 75/04 Polyurethanes
• CPC Class Codes: C09D 133/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C09D 133/10 Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C09D 133/12 Homopolymers or copolymers of methyl methacrylate

Abstract

A coating for implantable medical devices and a method for fabricating thereof are disclosed. The coating includes a mixture of a hydrophobic polymer and a polymeric hydrophilic additive, wherein the hydrophobic polymer and the hydrophilic additive form a physically entangled or interpenetrating system.

Claims

1. A method of fabricating a coating for an implantable medical device comprising:

providing an implantable medical device;

preparing a solution comprising at least one hydrophobic polymer comprising a macromolecular chain, at least one hydrophilic polymer comprising a macromolecular chain, and either a solvent or a blend of solvents;

applying the solution to the implantable medical device; and

removing the solvent or the blend of solvents;

wherein a physically entangled or intertwined system is formed of the

macromolecular chains of the hydrophobic polymer and the hydrophilic polymer; and

wherein at least one hydrophobic polymer is selected from the group consisting of polyurethaneureas with a Hildebrand solubility parameter (δ

) of less than 10.7 (cal/cm³)^1/2.

2. The method of claim 1, wherein the coating further comprises a drug.

3. The method of claim 1, wherein the hydrophilic polymer is selected from the group consisting of polyalkylene glycols, hyaluronic acid, chondroitan sulfate, chitosan, glucosaminoglucans, dextran, dextrin, dextran sulfate, cellulose acetate, carboxymethyl cellulose, hydroxyethyl cellulose, cellulosics, polypeptides, poly(2-hydroxyethyl methacrylate), polyacrylamide, polyacrylimide, poly(ethylene amine), poly(allyl amine), poly(vinyl pyrrolidone), poly(vinyl alcohol), poly(acrylic acid), poly(methacrylic acid), acrylic acid copolymers, methacrylic acid copolymers, polyvinyl alkyl ethers, non-ionic tetrafunctional block-copolymer surfactants, gelatin, collagen, albumin, chitin, heparin, elastin, fibrin, and mixtures thereof.

4. The method of claim 3, wherein the polyalkylene glycols are selected from the group consisting of poly(ethylene glycol), poly(ethylene oxide), poly(propylene glycol), poly(ethylene oxide-co-propylene oxide), poly(trimethylene glycol), poly(tetramethylene glycol), and mixtures thereof.

5. The method of claim 1, wherein the solution further comprises everolimus, 40-O-tetrazole-rapamycin, or a combination thereof.

6. The method of claim 1, wherein a mass ratio between the hydrophobic polymer and the hydrophilic polymer is between about 49:

1 and about 19;

1.

7. A method of fabricating a coating for an implantable medical device, comprising forming a coating on the device, the coating comprising a mixture of at least one hydrophobic polymer and at least one hydrophilic polymer;

wherein the macromolecular chains of the hydrophobic polymer and the hydrophilic polymer form a physically entangled or intertwined system;

and

wherein the hydrophobic polymer comprises poly(meth)acrylates

selected from the group consisting of poly(iso-propyl methacrylate), poly(iso-propyl acrylate), and mixtures thereof.

8. The method of claim 7, wherein the implantable medical device is a stent.

9. The method of claim 7, wherein the contour length of the hydrophilic polymer is in the range of about 10% to about 100% of the contour length of the hydrophobic polymer.

10. The method of claim 7, wherein the hydrophilic polymer is selected from a group consisting of polyalkylene glycols, hyaluronic acid, chondroitan sulfate, chitosan, glucosaminoglucans, dextran, dextrin, dextran sulfate, cellulose acetate, carboxymethyl cellulose, hydroxyethyl cellulose, cellulosics, polypeptides, poly(2-hydroxyethyl methacrylate), polyacrylamide, polyacrylimide, poly(ethylene amine), poly(allyl amine), poly(vinyl pyrrolidone), poly(vinyl alcohol), poly(acrylic acid), poly(methacrylic acid), acrylic acid copolymers, methacrylic acid copolymers, polyvinyl alkyl ethers, non-ionic tetrafunctional block-copolymer surfactants, gelatin, collagen, albumin, chitin, heparin, elastin, fibrin, and mixtures thereof.

11. The method of claim 10, wherein the polyalkylene glycols are selected from a group consisting of poly(ethylene glycol), poly(ethylene oxide), poly(propylene glycol), poly(ethylene oxide-co-propylene oxide), poly(trimethylene glycol), poly(tetramethylene glycol), and mixtures thereof.

12. The method of claim 7, wherein a mass ratio between the hydrophobic polymer and the hydrophilic polymer additive is between about 99:

1 and about 9;

1.

13. The method of claim 12, wherein the mass ratio between the hydrophobic polymer and the hydrophilic polymer is between about 74:

1 and about 14;

1.

14. The method of claim 13, wherein the mass ratio between the hydrophobic polymer and the hydrophilic polymer is between about 49:

1 and about 19;

1.

15. The method of claim 7, wherein the coating further comprises a drug.

16. The device of claim 15, wherein the drug is selected from a group consisting of rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, and combinations thereof.

17. The method of claim 7, wherein forming the coating on the device comprises:

preparing a solution by executing an operation comprising dissolving the at least one hydrophobic polymer comprising the macromolecular chain and the at least one hydrophilic polymer comprising the macromolecular chain in a solvent or a blend of solvents;

applying the solution to the implantable medical device; and

removing the solvent or the blend of solvents;

wherein the solvent or the blend of solvents has a vapor pressure of 30 Torr or higher at the temperature of coating formation.