Biocompatible polyacrylate compositions for medical applications

• US 8,871,236 B2
• Filed: 06/06/2013
• Issued: 10/28/2014
• Est. Priority Date: 12/11/2002
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Hossainy, Syed F. A.
• Primary Examiner(s): PURDY, KYLE A
• Application Number:
  US13/911,572
• Publication Number:
  US 20130273234A1
• Time in Patent Office: 509 Days
• US Class Current: 424/422
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• 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 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C08L 33/06 of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical

Abstract

A composition comprising a structural component comprising linear acrylic homopolymers or linear acrylic copolymers and a biobeneficial component comprising copolymers having an acrylate moiety and a biobeneficial moiety is disclosed. A medical article comprising the composition in the coating thereof and a method of fabricating the medical article are also disclosed.

Claims

1. A method for fabricating an implantable medical article comprising depositing a polymeric blend on at least a portion of the implantable medical device to form a coating, wherein the polymeric blend comprises:

(a) a biologically compatible structural component comprising a linear acrylic homopolymer or a linear acrylic copolymer, and

(b) a biobeneficial component comprising a copolymer having an acrylate moiety and a biobeneficial moiety,

wherein the copolymer composing the biobeneficial component has the formula;

2. The method of claim 1, wherein the implantable medical device is a stent.

3. The method of claim 1, wherein the mass ratio between the structural component and the biobeneficial component is between about 99:

1 and about 1;

1.

4. The method of claim 1, wherein the linear acrylic homopolymer or linear acrylic copolymer have the structure:

5. The method of claim 1, wherein the linear acrylic homopolymer and linear acrylic copolymer are synthesized by polymerizing monomers selected from a group consisting of methylmethacrylate, ethylmethacrylate, n-propyl methacrylate, iso-propylmethacrylate, n-butylmethacrylate, n-laurylmethacrylate, 2-hydroxyethylmethacrylate, and mixtures thereof.

6. The method of claim 1, further comprising preparing the polymeric blend which includes synthesizing the copolymer composing the biobeneficial component, wherein the copolymer composing the biobeneficial component is selected from the group consisting random, block, graft, and brush copolymers.

7. The method of claim 6, wherein the block copolymers include AB-, ABA-, BAB-, ABC-, or ABCBA-block copolymers.

8. The method of claim 6, wherein the step of synthesizing the block copolymers includes copolymerizing an acrylate and a biobeneficial monomer by a method of living, free-radical copolymerization with initiation-transfer agent termination of the living macro chains.

9. The method of claim 8, wherein the acrylate is methylmethacrylate, ethylmethacrylate, n-propyl methacrylate, iso-propylmethacrylate, n-butylmethacrylate, n-laurylmethacrylate, 2-hydroxyethylmethacrylate, or mixtures thereof.

10. The method of claim 8, wherein the biobeneficial monomer includes acryloyl-, methacryloyl-, vinyl, or allyl-modified adducts of superoxide dismutate-mimetics;

acryloyl-, methacryloyl-, vinyl, or allyl-modified diazenium diolate type nitric oxide donors;

acryloyl-, methacryloyl-, vinyl or allyl-modified adducts of phosphoryl choline;

or acryloyl-, methacryloyl-, vinyl, or allyl-modified polycationic peptides.

11. The method of claim 8 wherein the biobeneficial monomer is 2-acrylamido-2-methyl-1-propanesulfonic acid, poly(ethylene glycol) methacrylate, 3-sulfopropyl acrylate, 3-sulfopropyl acrylate methacrylate, N-vinylpyrrolidone, vinyl sulfonic acid, 4-styrene sulfonic acid, or 3-allyloxy-2-hydroxypropanesulfonic acid.

12. The method of claim 1, wherein the biobeneficial moiety includes fragments derived from poly(alkylene glycols), superoxide dismutate-mimetics (SODm), diazenium diolate type nitric oxide donors, polycationic peptides, polysaccharides, pyrrolidone, vitamin E, sulfonated dextrane, β

-phenoxyethanol, N,N-dimethylamino-2-ethanol, mannose-6-phosphate, sulfonic acid, derivatives of sulfonic acid, or mixtures thereof.

13. The method of claim 12, wherein the poly(alkylene glycols) are poly(ethylene glycol), poly(propylene glycol), poly(tetramethylene glycol), poly(ethylene glycol-co-propylene glycol), poly(ethylene oxide-co-propylene oxide), or mixtures thereof.

14. The method of claim 12, wherein the polycationic peptides are poly(L-arginine), poly(D-arginine), poly(D,L-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), a racemic mixture of poly(L-arginine) or poly(D-arginine), or mixtures thereof.

15. The method of claim 12, wherein the polysaccharides are heparin, heparin derivatives, glycosaminoglycans, keratan sulfate, chondroitin sulfate, dermatan sulfate, hyaluronic acid, hyaluronates, or mixtures thereof.

16. The method of claim 15, wherein the derivatives of heparin are heparinoids, heparin having a hydrophobic counterion, heparan sulfate, heparin salts, or mixtures thereof.

17. The method of claim 16, wherein the heparin salts are sodium heparin, potassium heparin, lithium heparin, calcium heparin, magnesium heparin, ardeparin sodium, or mixtures thereof.

18. The method of claim 12, wherein the derivatives of sulfonic acid are propanesulfonic acid, 2-methyl-1-propanesulfonic acid, benzenesulfonic acid, 3-methoxy-2-hydroxypropane sulfonic acid, or mixtures thereof.

19. The method of claim 1, wherein the mass ratio between the acrylate moiety and the biobeneficial moiety is between about 99:

1 and about 1;

1.

20. The method of claim 1, wherein the mass ratio between the acrylate moiety and the biobeneficial moiety is between about 19:

1 and about 9;

1.

21. The method of claim 1, wherein the mass ratio between the acrylate moiety and the biobeneficial moiety is about 3:

1.

22. The method of claim 1, wherein the copolymer composing the biobeneficial component is poly(ethylene glycol)-block-poly(n-butylmethacrylate)-block-poly(ethylene glycol), poly(n-butylmethacrylate)-block-poly(ethylene glycol)-block-poly(n-butylmethacrylate), or mixtures thereof.