COATINGS FOR DRUG DELIVERY DEVICES BASED ON POLY (ORTHOESTERS)

• US 20080071027A1
• Filed: 09/21/2007
• Published: 03/20/2008
• Est. Priority Date: 03/04/2003
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: PACETTI, STEPHEN
• Granted Patent: US 7,588,794 B2
• Time in Patent Office: Days
• US Class Current: 525/90
• CPC Class Codes: C08G 2650/42 containing orthoester groups
• CPC Class Codes: C08G 65/002 from unsaturated compounds unsaturated oxiranes C08G65/14
• CPC Class Codes: C08G 65/34 from hydroxy compounds or their metallic derivatives C08G65/26 takes precedence

Abstract

A polymer coating for implantable medical devices based on polyorthoesters and methods for fabricating the coating are disclosed. The implantable medical devices made of polyorthoesters and methods for fabricating thereof are also disclosed.

Claims

1. A coating for a medical device comprising:

a block copolymer and an additional polymer, wherein the block copolymer has a first block comprising a soft segment having a Tg below 37°

C. wherein the soft segment is a reaction product of a spirodiketene acetal and a non-fouling moiety selected from the group consisting of a poly(alkylene glycol), poly(ethylene oxide-co-propylene oxide) (PLURONIC®

), hydroxylated poly(vinyl pyrrolidone), dextran, dextrin, hyaluronic acid and derivatives thereof, poly(2-hydroxyethyl methacrylate) and mixtures thereof; and

,

a second block comprising a hard segment having a Tg above 37°

C. wherein the hard segment is a reaction product of a spirodiketene acetal and a C₂-C₁₆ alkylene glycol, a cycloaliphatic diol, a cyclohexanedimethanol, and an oligoaliphatic diol selected from the group consisting of diethylene glycol, triethylene glycol or tetraethylene glycol.

2. The coating of claim 1 wherein the medical device is a stent.

3. The coating of claim 1 wherein the diketene acetal has the formula

4. The coating of claim 1 wherein the diketene acetal is one of 3,9-diethylidene-2,4,8,10-tetraoxaspiro-[5,5]-undecane, 3,9-dipentylidene-2,4,8,10-tetraoxaspiro-[5,5]-heptadecane, 3,9-dibutylidene-2,4,8,10-tetraoxaspiro-[5,5]-pentadecane, 3,9-dipropylidene-2,4,8,10-tetraoxaspiro-[5,5]-tridecane, or mixtures thereof.

5. The coating of claim 1 wherein the hydroxylated functional compound comprises poly(alkylene glycols), hydroxylated poly(vinyl pyrrolidone), dextran, dextrin, hyaluronic acid, derivatives of hyaluronic acid, poly(2-hydroxyethyl methacrylate), or mixtures thereof.

6. The coating of claim 5, wherein poly(alkylene glycols) are selected from the group consisting of poly(ethylene glycol), poly(propylene glycol), poly(tetramethylene glycol), and poly(ethylene oxide-co-propylene oxide).

7. The coating of claim 6, wherein the diol comprises alkylene glycols, oligoalkylene glycols, or cycloaliphatic diols.

8. The coating of claim 7, wherein alkylene glycols are one of ethylene glycol, propylene glycol, butane-1,4-diol, pentane-1,5-diol, hexane-1,6-diol, heptane-1,7-diol, octane-1,8-diol, nonane-1,9-diol, decane-1,10-diol, undecane-1,11-diol, dodecane-1,12-diol, tridecane-1,13-diol, tetradecane-1,14-diol, pentadecane-1,15-diol, hexadecane-1,16-diol, butane-1,3-diol, pentane-2,4-diol, hexane-2,5-diol, or mixtures thereof.

9. The coating of claim 7, wherein oligoalkylene glycols are one of diethylene glycol, trimethylene glycol, tetramethylene glycol, tetraethylene glycol, or mixtures thereof.

10. The coating of claim 7, wherein cycloaliphatic glycols are one of trans-cyclohexanedimethanol, 1,4-cyclohexanediol, or mixtures thereof.

11. A method for fabricating a coating for an implantable medical device, the method comprising applying the coating of claim 1 onto the surface of the device.

12. The method of claim 11, wherein the medical device is a stent.

13. The method of claim 11, wherein the diketene acetal has a formula

14. The method of claim 11, wherein the diketene acetal is selected from a group consisting of include 3,9-diethylidene-2,4,8,10-tetraoxaspiro-[5,5]-undecane, 3,9-dipentylidene-2,4,8,10-tetraoxaspiro-[5,5]-heptadecane, 3,9-dibutylidene-2,4,8,10-tetraoxaspiro-[5,5]-pentadecane, 3,9-dipropylidene-2,4,8,10-tetraoxaspiro-[5,5]-tridecane, and mixtures thereof.

15. The method of claim 11, wherein the hydroxylated functional compound comprises poly(alkylene glycols), hydroxylated poly(vinyl pyrrolidone), dextran, dextrin, hyaluronic acid, derivatives of hyaluronic acid, poly(2-hydroxyethyl methacrylate), or mixtures thereof.

16. The method of claim 15, wherein poly(alkylene glycols) are selected from a group consisting of poly(ethylene glycol), poly(propylene glycol), poly(tetramethylene glycol), and poly(ethylene oxide-co-propylene oxide).

17. The method of claim 11, wherein the diol comprises alkylene glycols, oligoalkylene glycols, or cycloaliphatic diols.

18. The method of claim 17, wherein alkylene glycols are selected from a group consisting of ethylene glycol, propylene glycol, butane-1,4-diol, pentane-1,5-diol, hexane-1,6-diol, heptane-1,7-diol, octane-1,8-diol, nonane-1,9-diol, decane-1,10-diol, undecane-1,1′

-diol, dodecane-1,12-diol, tridecane-1,13-diol, tetradecane-1,14-diol, pentadecane-1,15-diol, hexadecane-1,16-diol, butane-1,3-diol, pentane-2,4-diol, hexane-2,5-diol, or mixtures thereof.

19. The method of claim 17, wherein oligoalkylene glycols are selected from a group consisting of diethylene glycol, trimethylene glycol, tetramethylene glycol, tetraethylene glycol, and mixtures thereof.

20. The method of claim 17, wherein cycloaliphatic diols are selected from a group consisting of trans-cyclohexanedimethanol, 1,4-cyclohexanediol, and mixtures thereof.

21. An implantable medical device made of the coating of claim 1.

22. The coating of claim 1 wherein the additional polymer is one of poly(ethylene-co-vinyl alcohol), poly(hydroxyvalerate), poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane;

poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), co-poly(ether-esters) polyalkylene oxalates, polyphosphazenes, biomolecules, fibrin, fibrinogen, cellulose, starch, collagen, hyaluronic acid, polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymers, acrylic copolymers, vinyl halide polymers, vinyl halide copolymers, polyvinyl chloride, polyvinyl ethers, polyvinyl methyl ether, polyvinylidene halides, polyvinylidene fluoride, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics polystyrene, polyvinyl esters, polyvinyl acetate, copolymers of vinyl monomers with each other and olefins, ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides, Nylon 66, polycaprolactam, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, soluble fluorinated polymers, carboxymethyl cellulose and mixtures thereof.