Copolymers having zwitterionic moieties and dihydroxyphenyl moieties and medical devices coated with the copolymers

• US 8,202,956 B2
• Filed: 03/10/2011
• Issued: 06/19/2012
• Est. Priority Date: 11/21/2006
• Status: Active Grant

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Pacetti, Stephen
• Primary Examiner(s): Lipman, Bernard
• Application Number:
  US13/045,452
• Publication Number:
  US 20110160382A1
• Time in Patent Office: 467 Days
• Field of Search: 526/277, 526/312, 526/320, 526/328.5
• US Class Current: 526/277
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: C08L 27/18 Homopolymers or copolymers or tetrafluoroethene

Abstract

Copolymers are manufactured to include a zwitterionic monomer (e.g., methacryloyloxyethyl phosphorylcholine monomer), a dihydroxyphenyl derivatized monomer, and optionally one or more additional monomers. The dihydroxyphenyl derivatized monomer gives the copolymers excellent adhesion properties. Optional monomers include a cationic amino monomer, a hydrocarbon monomer, and/or a hydrophilic monomer. The copolymers are biocompatible and can be used with medical devices.

Claims

1. A medical device comprising a supporting structure having a coating associated therewith, the coating comprising a polymer having the formula,

2. The medical device as in claim 1, in which n+o+p+q+r=1.

3. The medical device as in claim 1, in which the 3,4-dihydroxyphenyl group is substituted with a 2,3-dihydroxyphenyl group.

4. The medical device as in claim 1, in which the zwitterion group is selected from the group consisting of phosphorylcholine, phosphoryl ethanolamine, phosphatidyl ethanolamine, phosphoethanolamine, phosphatidyl serine, and combinations thereof.

5. The medical device as in claim 1, in which the glass transition temperature of the polymer when hydrated is in a range from about −

30°

C. to about 37°

C.

6. The medical device as in claim 1, in which the glass transition temperature of the polymer when dry is in a range from about −

30°

C. to about 100°

C.

7. The medical device as in claim 1, in which the polymer is substantially free of cross-linking.

8. The medical device as in claim 1, in which the polymer having the formula,

9. The medical device as in claim 8, in which R₆ is selected from the group consisting of phosphorylcholine, phosphoryl ethanolamine, phosphatidyl ethanolamine, phosphoethanolamine, phosphatidyl serine, and combinations thereof.

10. The medical device as in claim 1, in which the polymer having the formula,

11. The medical device as in claim 1, in which the polymer having the formula,

12. The medical device as in claim 1, in which the molecular weight of the polymer is in a range from about 20 kpa to about 800 kpa.

13. The medical device as in claim 1, in which the molecular weight of the polymer is in a range from about 2 kpa to about 200 kpa.

14. The medical device as in claim 1, in which the biocompatible coating further comprising a polymer selected from the group consisting of poly(vinyl pyrrolidinone), poly(n-butyl methacrylate), poly(n-butyl methacrylate) copolymers, methacrylate polymers, acrylate polymers, and/or a terpolymers of hexyl methacrylate, vinyl acetate, and vinyl pyrrolidinone.

15. The medical device as in claim 1, wherein the zwitterion has formula

16. The medical device as in claim 15, wherein the W⁺ is a (CH)₂⁺N(R²)₃, where R² are the same or different and each is hydrogen or C_1-4 alkyl, and m is from 1 to 4.

17. The medical device as in claim 1, wherein the zwitterion has formula

-A⁴-R³—

N⁺(R⁴)₂—

R⁵—

V⁻

, wherein A⁴ is a valence bond, —

O—

, —

S—

, or —

NH—

;

V is a carboxylate or phosphate diester (monovalently charged) anion;

R³ is a valence bond (together with A⁴) or alkanediyl, —

C(O)alkylene- or —

C(O)NH alkylene;

the groups R⁴ are the same or different and each is hydrogen or alkyl of 1 to 4 carbon atoms or the groups R⁴ together with the nitrogen to which the are attached form a heterocyclic ring of 5 to 7 atoms; and

R⁵ is an alkyanediyl of 1 to 20 carbon atoms, of 1 to 10 carbon atoms, or of 1 to 6 carbon atoms.

18. The medical device as in claim 1, wherein the zwitterion has formula

19. The medical device as in claim 1, which is an implantable device selected from the group consisting of coronary stents, peripheral stents, catheters, arteriovenous grafts, by-pass grafts, pacemaker, and defibrillator leads, anastomotic clips, arterial closure devices, patent foramen ovale closure devices, and drug delivery balloons.

20. The medical device as in claim 1, which is a stent.