ZWITTERIONIC COPOLYMERS, METHOD OF MAKING AND USE ON MEDICAL DEVICES

• US 20080147178A1
• Filed: 11/19/2007
• Published: 06/19/2008
• Est. Priority Date: 11/21/2006
• Status: Active Grant

• Current Assignee: Abbott Laboratories
• Original Assignee: Abbott Laboratories
• Inventors: Pacetti, Stephen, Roorda, Wouter
• Granted Patent: US 7,781,551 B2
• Time in Patent Office: Days
• US Class Current: 623/1.46
• 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

Biocompatible copolymers are manufactured to include a zwitterionic monomer and an alkoxy acrylate monomer. The alkoxy acrylate monomer can be a 2-methoxyethyl methacrylate (MOEMA) or a 2-methoxyethyl methacrylate (EOEMA). Alternatively, the alkoxy acrylate can be 2-methoxyethyl acrylate (MOEA) or 2-ethoxyethyl acrylate (EOEA). The alkoxy acrylate monomers advantageously give the zwitterionic copolymers greater ductility, strength, and toughness while maintaining a desired amount of hydrophilicity. The improved toughness allows the zwitterionic copolymers to be processed without cross-linking, which improves the elongation properties of the zwitterionic copolymer, and reduces the risk of cracking during use.

Claims

1. A method for manufacturing a biocompatible polymer, comprising:

polymerizing a plurality of acrylate monomers to yield a thermoplastic polymer having the following formula,

2. A method 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.

3. A method as in claim 1, in which the copolymer is formed by reacting a alkoxy acrylate monomer with a zwitterionic acrylate monomer.

4. A method as in claim 1, in which the plurality of acrylate monomers are polymerized to form an intermediate polymer and the zwitterionic group or the alkoxy group is thereafter coupled to the intermediate polymer to yield the copolymer.

5. A method as in claim 4, in which the zwitterionic group is coupled to an acrylate monomer of the intermediate polymer.

6. A method as in claim 5, in which the coupling of the zwitterionic group to the intermediate polymer is carried out by a transesterification process in which an ester bond is formed between a zwitterionic compound and an acrylate monomer of the intermediate polymer.

7. A method as in claim 4, in which the alkoxy group is coupled to an acrylate monomer of the intermediate polymer.

8. A method as in claim 7, in which the coupling of the alkoxy group to the intermediate polymer is carried out by a transesterification process in which an ester bond is formed between an alkoxy compound and an acrylate monomer of the intermediate polymer.

9. A method as in claim 1, in which the ratio of zwitterionic monomer and alkoxy acrylate monomer is selected to yield a thermoplastic polymer with a hydrated glass transition temperature in a range from about −

30°

C. to about 37°

C.

10. A method as in claim 1, in which the ratio of zwitterionic monomer and alkoxy acrylate monomer is selected to yield a thermoplastic polymer with a dry glass transition temperature in a range from about −

30°

C. to about 100°

C.

11. A method as in claim 1, in which the thermoplastic polymer is substantially free of cross-linking.

12. A method as in claim 1, in which the copolymer has a number average molecular weight in a range from about 20K to about 800K.

13. A method as in claim 1, in which the copolymerization reaction is carried out using free radical polymerization, atom transfer radical polymerization, cationic polymerization, anionic polymerization, or iniferter polymerization.

14. A method as in claim 1, in which the thermoplastic polymer is mixed with at least one bioactive agent to form a drug coating.

15. A biocompatible polymer manufactured according to the method of claim 1.

16. A method for using a biocompatible polymer on a medical device, comprising:

providing a medical device comprising a supporting structure;

coating at least a portion of the supporting structure with a coating comprising a copolymer having the following formula,

17. A method as in claim 16, in which the step of coating the support structure comprises,

dissolving the copolymer in a solvent to form a copolymer solution;

and

applying the copolymer solution to the supporting structure.

18. A biocompatible polymer comprising:

19. A biocompatible polymer as in claim 18, in which R₅ is a methyl.

20. A biocompatible polymer as in claim 18, in which R₅ is an ethyl.

21. A medical device coating comprising the biocompatible polymer of claim 18.

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

23. A medical device as in claim 22, in which R₅ is a methyl.

24. A medical device as in claim 22, in which R₅ is an ethyl.

25. A medical device as in claim 22, in which the polymer has the formula,

26. A medical device as in claim 22, in which the polymer has the formula,