Polymer coating for medical devices

• US 7,364,768 B2
• Filed: 11/28/2006
• Issued: 04/29/2008
• Est. Priority Date: 02/15/2002
• Status: Expired due to Fees

• Current Assignee: CV Therapeutics Inc (Gilead Sciences Inc.)
• Original Assignee: CV Therapeutics Inc (Gilead Sciences Inc.)
• Inventors: Rypacek, Frantisek, Machova, Ludka, Lapcikova, Monika
• Primary Examiner(s): Fletcher, III; William Phillip
• Assistant Examiner(s): Sellman; Cachet I
• Application Number:
  US11/605,634
• Publication Number:
  US 20070071879A1
• Time in Patent Office: 518 Days
• Field of Search: 427/2.24, 427/2.1, 427/2.13, 427/2.28, 427/2.29, 428/36.91, 428/447, 428/448, 428/450, 428/480, 424422-426, 623/1.38, 623/1.42, 623/1.44, 623/1.46
• US Class Current: 427/2.1
• CPC Class Codes: A61L 2300/606 Coatings
• 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 33/0076 Chemical modification of the substrate
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 83/04 Polysiloxanes
• CPC Class Codes: Y10T 428/1352 Polymer or resin containing [i.e., natural or synthetic]
• CPC Class Codes: Y10T 428/139 Open-ended, self-supporting conduit, cylinder, or tube-type article
• CPC Class Codes: Y10T 428/1393 Multilayer [continuous layer]
• CPC Class Codes: Y10T 428/31663 As siloxane, silicone or silane
• CPC Class Codes: Y10T 428/31786 Of polyester [e.g., alkyd, etc.]

Abstract

Coatings are provided in which surfaces may be activated by covalently bonding a silane derivative to the metal surface, covalently bonding a lactone polymer to the silane derivative by in situ ring opening polymerization, and depositing at least one layer of a polyester on the bonded lactone. Biologically active agents may be deposited with the polyester layers. Such coated surfaces may be useful in medical devices, in particular stents.

Claims

1. A method for coating a medical device comprising:

(a) reacting the surface of a medical device with a silane-based activating reagent to form a polymerized silane derivative covalently bonded to the surface of the medical device, said polymerized silane derivative containing hydroxyl or other functional groups that can be transformed into hydroxyl groups;

(b) reacting the device of step (a) with at least one lactone monomer in the presence of a metal catalyst to form a lactone polymer chain covalently bonded to the polymerized silane derivative, said chains grown on the hydroxyl or amino functional groups of the silane derivative through in-situ ringopening graft polymerization of lactone monomers, said polymerization initiated by said hydroxyl or amino functional groups of the silane derivative covalently bonded to the surface of the medical device, said lactone polymer chains and said silane derivative together forming a grafted lactone polymer layer; and

(c) treating the device of step (b) with at least one polyester polymer layer deposited on the grafted lactone polymer layer, wherein at least the first of the deposited polyester polymer layers is chemically compatible with the grafted lactone polymer layer to allow for entanglement of said deposited polyester polymer chains with the chains of said grafted lactone polymer chains for strong adhesion.

2. The method of claim 1 wherein the silane-based activating reagent comprises a compound of the formula R¹—

Si(R²)₃, wherein R¹ is independently selected from substituted alkyl, substituted alkenyl, substituted alkynyl, substituted araalkyl, substituted heteroaryl, and substituted alkoxy, with the proviso that R¹ contains a hydroxy or amino group, or a functional group that can be transformed to a radical that contains a hydroxy or amino group, wherein R² is independently selected from halo, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted silyloxy, or optionally substituted alkyl, with the proviso that all three R² substituents are not simultaneously substituted alkyl.

3. The method of claim 1 wherein step (c) is repeated two or more times to provide multiple layers of polyester polymer deposited on the covalently grafted lactone polymer layer.

4. The method of claim 3 that further comprises depositing a barrier or skin layer on top of the deposited polyester polymer layers.

5. The method of claim 4 wherein the barrier or skin layer comprises a lactone polymer.

6. The method of claim 5 wherein the lactone polymer comprises polyglycolide, poly(L-lactide), poly(D-lactide), poly(ε

-caprolactone), poly(p-dioxanone), poly(dioxepanone), poly(D,L-lactide), poly(L-lactide-co-D-lactide), poly(L-lactide-co-glycolide), poly(D-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(lactide-co-caprolactone), poly(lactide-co-dioxanone), or poly(lactide-co-dioxepanone).

7. The method of claim 1 that further comprises depositing a barrier or skin layer on top of the deposited polyester polymer layer.

8. The method of claim 7 wherein the barrier or skin layer comprises a lactone polymer.

9. The method of claim 8 wherein the lactone polymer comprises polyglycolide, poly(L-lactide), poly(D-lactide), poly(ε

-caprolactone), poly(p-dioxanone), poly(dioxepanone), poly(D,L-lactide), poly(L-lactide-co-D-lactide), poly(L-lactide-co-glycolide), poly(D-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(lactide-co-caprolactone), poly(lactide-co-dioxanone), or poly(lactide-co-dioxepanone).

10. The method of claim 1 wherein the polyester polymer layer deposited on the grafted lactone polymer layer comprises two or more polyester polymer sublayers.

11. The method of claim 10 wherein the deposited polyester polymer sublayers each independently comprise a lactone polymer, wherein the lactone polymer comprises polyglycolide, poly(L-lactide), poly(D-lactide), poly(ε

-caprolactone), poly(p-dioxanone), poly(dioxepanone), poly(D,L-lactide), poly(L-lactide-co-D-lactide), poly(L-lactide-co-glycolide), poly(D-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(lactide-co-caprolactone), poly(lactide-co-dioxanone), or poly(lactide-co-dioxepanone).

12. The method of claim 11 wherein the deposited polyester polymer layer comprises poly(L-lactide) or poly(D,L-lactide).

13. The method of claim 1 wherein the polyester polymer layer of step (c) is deposited by spray coating.

14. The method of claim 1 wherein the polyester polymer layer deposited includes a biologically active agent.

15. The method of claim 1 wherein the coated device is sterilized prior to use.