Methods of manufacturing copolymers with zwitterionic moieties and dihydroxyphenyl moieties and use of same

• US 8,101,156 B2
• Filed: 11/19/2007
• Issued: 01/24/2012
• Est. Priority Date: 11/21/2006
• Status: Expired due to Fees

• Current Assignee: Abbott Laboratories
• Original Assignee: Abbott Laboratories
• Inventors: Pacetti, Stephen
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US11/942,704
• Publication Number:
  US 20080153923A1
• Time in Patent Office: 1,527 Days
• Field of Search: None
• US Class Current: 424/1.65
• 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 method for manufacturing a biocompatiblc polymer, comprising

copolymerizing a zwitterion monomer with a dihydroxyphenyl monomer to yield a thermoplastic polymer having the following chemical formula,

2. The method as in claim 1, wherein the 3,4-dihydroxyphenyl group is substituted with a 2,3-dihydroxyphenyl group.

3. The method as in claim 1, wherein n+o+p+q+r=1.

4. The method as in claim 1, in which the thermoplastic polymer has a glass transition temperature in a range from about −

30°

C. to about 37°

C., when hydrated.

5. The method as in claim 1, in which the thermoplastic polymer has a glass transition temperature in a range from about −

30°

C. to about 100°

C., when dry.

6. The method as in claim 1, in which the copolymerization further comprises copolymerizing a cationic amino monomer to yield a thermoplastic polymer that includes cationic amino groups.

7. The method as in claim 6, in which the cationic amino monomer is selected from the group consisting of N,N-diethylaminoethyl methacrylate, 2-(dimethylamino)ethyl methacrylate, 2-aminoethyl methacrylate, N-(3-aminopropyl)methacrylamide, 2-(diethylamino)ethyl styrene, 2-(dimethylamino)ethyl acrylate, N-(2-(N,N′

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

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

-dimethylamino)propyl methacrylamide, and combinations thereof.

8. The method as in claim 1, in which the copolymerization further comprises copolymerizing a hydrocarbon monomer to yield a copolymer that includes hydrocarbon groups.

9. The method as in claim 8, in which the hydrocarbon monomer is 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, trimethylcyclohcxyl methacrylate, n-dodecyl methacrylate, methacrylates with pendant groups comprising up to 16 carbons, 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, isobutylene.

10. The method as in claim 1, in which the copolymerization further comprises copolymerizing a hydrophilic monomer to yield a copolymer that includes hydrophilic groups.

11. The method as in claim 10, wherein the hydrophilic monomer is selected from the group consisting of hydroxyethyl methacrylate, hydroxy propyl methacrylate, 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, styrene sulfonic acid, and combinations thereof.

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

13. The method as in claim 1, in which the thermoplastic polymer has a number average molecular weight in a range from about 20 kDa to about 800 kDa.

14. The method as in claim 1, in which the thermoplastic polymer has a number average molecular weight in a range from about 100 kDa to about 600 kDa.

15. The method as in claim 1, in which the thermoplastic polymer has a number average molecular weight in a range from about 2 kDa to about 200 kDa.

16. The method as in claim 1, further comprising forming the dihydroxyphenyl monomer by reacting a dihydroxyphenyl compound with a polymerizable group.

17. The 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.

18. The method as in claim 1, in which the biocompatible polymer is mixed with at least one bioactive agent to form a drug coating.