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

• US 8,399,584 B2
• Filed: 03/10/2011
• Issued: 03/19/2013
• 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): Choi, Ling
• Assistant Examiner(s): WANG, CHUN CHENG
• Application Number:
  US13/045,450
• Publication Number:
  US 20110166250A1
• Time in Patent Office: 740 Days
• Field of Search: 526/277, 523/113
• 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 biocompatible polymer having the formula,

2. The biocompatible polymer as in claim 1, wherein n+o+p+q+r=1.

3. The biocompatible polymer as in claim 1, in which the zwitterion group is selected from the group consisting of phosphorylcholine, phosphoryl ethanolamine, phosphatidyl ethanolamine, phosphoethanolamine, phosphatidyl serine, sulfobetaine and combinations thereof.

4. The biocompatible polymer 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.

5. The biocompatible polymer 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.

6. The biocompatible polymer as in claim 1, in which the polymer is substantially free of cross-linking.

7. A medical device coating comprising the biocompatible polymer of claim 1.

8. The biocompatible polymer as in claim 1, having the formula,

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

10. The biocompatible polymer as in claim 1 having the formula,

11. A medical device coating comprising the biocompatible polymer of claim 10.

12. The biocompatible polymer as in claim 1, having the formula,

13. A medical device coating comprising the biocompatible polymer of claim 12.

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

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

16. A biocompatible coating comprising the biocompatible polymer of claim 1 blended with 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/of a terpolymers of hexyl methacrylate, vinyl acetate, and vinyl pyrrolidinone.

17. The biocompatible polymer as in claim 1, in which the zwitterionic group having the following general formula

18. The biocompatible polymer as in claim 17, in which the W⁺ is a (CH₂)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.

19. The biocompatible polymer as in claim 1, in which the zwitterionic group is a betaine group.

20. The biocompatible polymer as in claim 19, in which the betaine group is a sulpho-, carboxy- or phosphor-betaine.

21. The biocompatible polymer as in claim 19, in which the betaine group has the formula -A⁴-R³—

N⁺(R⁴)₂—

R⁵—

V⁻

, in which

A⁴ is a valence bond, —

O—

, —

S—

, or —

NH—

;

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

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

C(O)alkylene- or —

C(O)NH alkylene;

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

R⁷ is an alkanediyl of 1 to 20 carbon atoms, of 1 to 10 carbon atoms, or of 1 to 6 carbon atoms.

22. The biocompatible polymer as in claim 1, in which the zwitterionic group is an amino acid moiety in which the alpha carbon atom is joined through a linker group to the backbone of the copolymer, represented by the following general formula

23. A biocompatible polymer having the formula,

24. The biocompatible polymer as in claim 23, wherein n+o+p+q+r=1.

25. The biocompatible polymer as in claim 23, in which the zwitterion group is selected from the group consisting of phosphorylcholine, phosphoryl ethanolamine, phosphatidyl ethanolamine, phosphoethanolamine, phosphatidyl serine, sulfobetaine and combinations thereof.

26. The biocompatible polymer as in claim 23, in which the zwitterionic group having the following general formula

27. The biocompatible polymer as in claim 23, in which the zwitterionic group is an amino acid moiety in which the alpha carbon atom is joined through a linker group to the backbone of the copolymer, represented by the following general formula

28. The biocompatible polymer as in claim 23, in which the molecular weight of the polymer is in a range from about 20 kDa to about 800 kDa.

29. The biocompatible polymer as in claim 23, in which the glass transition temperature of the polymer when dry is in a range from about −

30°

C. to about 100°

C.

30. A medical device coating comprising the biocompatible polymer of claim 23.

31. A medical device coating comprising the biocompatible polymer of claim 23 blended with 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 a terpolymers of hexyl methacrylate, vinyl acetate, and vinyl pyrrolidinone.