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

• US 8,846,839 B2
• Filed: 02/23/2012
• Issued: 09/30/2014
• Est. Priority Date: 11/21/2006
• Status: Expired due to Fees

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Pacetti, Stephen
• Primary Examiner(s): Mulcahy, Peter D
• Application Number:
  US13/403,777
• Publication Number:
  US 20120157602A1
• Time in Patent Office: 950 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 cationic amino group is derived from a cationic amino group containing monomer selected from the group consisting of N,N′

-diethylaminoethyl methacrylate, 2-(dimethylamino)ethyl methacrylate, 2-aminoethyl methacrylate, N-(3-aminopropyl)methacrylamide, 2-(dimethylamino)ethyl styrene, 2-(dimethylamino)ethyl acrylate, N-(2-(N,N′

-dimethylamino)ethyl)methacrylamide, N-(3-(N,N′

-dimethylamino)propyl)acrylamide, and N-(3-N,N′

-dimethylamino)propyl methacrylamide.

4. The medical device as in claim 1, in which the hydrocarbon group is derived from a hydrocarbon group containing monomer selected from the group consisting of ethyl methacrylate, n-butyl methacrylate, lauryl-methacrylate, methyl methacrylate, isopropyl methacrylate, n-propyl methacrylate, isobutyl methacrylate, sec-butyl methacrylate, tert-butyl methacrylate, n-hexyl methacrylate, cyclohexyl methacrylate, 2-ethylhexyl methacrylate, phenyl methacrylate, benzyl methacrylate, isobornyl methacrylate, trimethylcyclohexyl methacrylate, n-dodecyl methacrylate, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate, isobutyl acrylate, sec-butyl acrylate, n-hexyl acrylate, cyclohexyl acrylate, phenyl acrylate, benzyl acrylate, styrene, alkyl substituted styrene, ethylene, propylene, 1-butene, and isobutylene.

5. The medical device as in claim 1, in which the hydrophilic group is derived from a hydrophilic group containing monomer selected from the group consisting of hydroxyethyl methacrylate (HEMA), hydroxy propyl methacrylate (HPMA), acrylamide, methacrylamide, hydroxyalkyl methacrylamides, 2-hydroxyethyl methacrylate, 3-hydroxypropyl methacrylate, 2-hydroxypropyl methacrylate, hydroxybutyl methacrylate, acrylic acid, methacrylic acid, 2-methoxyethyl acrylate, 2-methoxyethyl methacrylate, 2-ethoxyethyl methacrylate, PEG-methacrylate, PEG-acrylate, polypropylene glycol acrylate, polypropylene glycol methacrylate, vinyl pyrrolidone, allyl alcohol, vinyl sulfonic acid, 2-sulfoethyl methacrylate, 3-sulfopropyl methacrylate, and styrene sulfonic acid.

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

7. The medical device as in claim 6, wherein the W⁺ is a (CH₂)_m⁺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.

8. 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 they 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.

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

10. 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.

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

12. The medical device as in claim 11, in which R₆ is selected from the group consisting of phosphorylcholine, phosphoryl ethanolamine, phosphatidyl ethanolamine, phosphoethanolamine, phosphatidyl serine, and combinations thereof.

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

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

15. 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.

16. 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.

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

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

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

20. 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 terpolymers of hexyl methacrylate, vinyl acetate, and vinyl pyrrolidinone.

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

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