Methods for manufacturing amino acid mimetic copolymers and use of same

• US 8,658,749 B2
• Filed: 10/08/2009
• Issued: 02/25/2014
• 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): EGWIM, KELECHI CHIDI
• Application Number:
  US12/575,720
• Publication Number:
  US 20100022663A1
• Time in Patent Office: 1,601 Days
• Field of Search: 526/307.8, 526/303.1, 526/306
• US Class Current: 526/307.8
• 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 polymers are manufactured to include an ammo acid mimetic monomer and one or more hydrophobic acrylate monomers. The amino acid mimetic monomers are selected to mimic the side chain of the amino acids asparagine or glutamine. The amino acid mimetic monomer can be a methacryloyl or acryloyl derivative of 2-hydroxyacetamide, 3-hydroxypropionamide, alaninamide, lactamide, or glycinamide. These amide functional groups offer the advantage of moderate hydrophilicity with little chemical reactivity. The amino acid mimetic monomer can be copolymerized with one or more hydrophobic acrylate monomers to obtain desired coating properties.

Claims

1. A biocompatible polymer prepared according to a method comprising:

copolymerizing a plurality of acrylate monomers to yield a copolymer having the following formula,

2. The biocompatible polymer of claim 1, in which the copolymer is formed by reacting a hydrophobic monomer with an amino acid mimetic monomer.

3. The biocompatible polymer of claim 1, in which the plurality of acrylate monomers are polymerized to form an intermediate polymer and the hydrophobic group or the amino acid mimetic group is thereafter coupled to the intermediate polymer to yield the copolymer.

4. The biocompatible polymer of claim 3, in which the hydrophobic group is coupled to an acrylate monomer of the intermediate polymer.

5. The biocompatible polymer of claim 4, in which the coupling of the hydrophobic group to the intermediate polymer is carried out by a transesterification process in which an ester bond is formed between a hydrophobic compound and an acrylate monomer of the intermediate polymer.

6. The biocompatible polymer of claim 3, in which the amino acid mimetic group is coupled to an acrylate monomer of the intermediate polymer.

7. The biocompatible polymer of claim 6, in which the coupling of the amino acid mimetic group to the intermediate polymer is carried out by a transesterification process in which an ester bond is formed between an amino acid mimetic compound and an acrylate monomer of the intermediate polymer.

8. The biocompatible polymer of claim 1, in which the hydrophobic group is selected from the group consisting of a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, 2-ethyl-hexyl, n-hexyl, cyclohexyl, n-hexyl, isobornyl, or trimethylcyclohexyl, and combinations thereof.

9. The biocompatible polymer of claim 1, in which R₁ is a methyl group.

10. The biocompatible polymer of claim 1, in which R₂ is a methyl group.

11. The biocompatible polymer of claim 1, in which the concentration of the hydrophobic monomer and the concentration of the amino acid mimetic monomer are selected to yield a thermoplastic polymer with a hydrated glass transition temperature in a range from about −

30°

C. to about 37°

C.

12. The biocompatible polymer of claim 1, in which the concentration of the hydrophobic monomer and the concentration of the amino acid mimetic monomer are selected to yield a thermoplastic polymer with a hydrated glass transition temperature in a range from about 0°

C. to about 37°

C.

13. The biocompatible polymer of claim 1, in which the concentration of the hydrophobic monomer and the concentration of the amino acid mimetic monomer are selected to yield a thermoplastic polymer with a dry glass transition temperature in a range from about −

30°

C. to about 100°

C.

14. The biocompatible polymer of claim 1, in which the concentration of the hydrophobic monomer and the concentration of the amino acid mimetic monomer are selected to yield a thermoplastic polymer with a dry glass transition temperature in a range from about 0°

C. to about 70°

C.

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

16. The biocompatible polymer of claim 1, in which the copolymer has a number average molecular weight in a range from about 20K to about 800K.

17. The biocompatible polymer of claim 1, in which the copolymer has a number average molecular weight in a range from about 100K to about 600K.

18. The biocompatible polymer of claim 1, in which the copolymer has a number average molecular weight in a range from about 2K to about 200K.

19. The biocompatible polymer of 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.

20. The biocompatible polymer of claim 1, which is mixed with at least one bioactive agent to form a drug coating.

21. The biocompatible polymer of claim 1, having a formula selected from the group consisting of the following: