Coatings of acrylamide-based copolymers

• US 8,017,141 B2
• Filed: 12/15/2006
• Issued: 09/13/2011
• Est. Priority Date: 12/15/2006
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Glauser, Thierry, Hossainy, Syed F. A., Trollsas, Mikael O.
• Primary Examiner(s): Hartley; Michael G
• Assistant Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US11/639,860
• Publication Number:
  US 20080146992A1
• Time in Patent Office: 1,733 Days
• Field of Search: 424/423
• US Class Current: 424/423
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• 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: C08L 33/26 Homopolymers or copolymers of acrylamide or methacrylamide

Abstract

An implantable device including conjugate formed of an acrylamide-based copolymer and a bioactive agent is provided.

Claims

1. An implantable device comprising a coating, the coating comprising a conjugate of a bioactive agent and poly[N-(2-hydroxypropyl)methacrylamide-co-methoxyethyl methacrylate] copolymer (HPMA-co-MOEMA).

2. The implantable device of claim 1, wherein the conjugate comprises covalent bonding between the bioactive agent and the copolymer.

3. The implantable device of claim 2, wherein the conjugate further comprises a linker.

4. The implantable device of claim 2, wherein the conjugate further comprises poly(ethylene glycol) (PEG), an alkyl chain, or a peptide sequence.

5. The implantable device of claim 4, wherein the peptide sequence comprises glycine-phenylalinine-leucine-glycine.

6. The implantable device of claim 1, wherein the copolymer is a random or block copolymer.

7. The implantable device of claim 1, which is a stent.

8. The implantable device of claim 1, wherein the bioactive agent is selected from the group consisting of halofuginone, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole -rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.

9. The implantable device of claim 7, wherein the bioactive agent is selected from the group consisting of halofuginone, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.

10. The implantable device of claim 1, wherein the coating is a matrix.

11. The implantable device of claim 1, wherein the coating is a topcoat.

12. A method of forming a coating on an implantable device, comprising

providing poly[N-(2-hydroxypropyl)methacrylamide-co-methoxyethyl methacrylate] copolymer (HPMA-co-MOEMA),

providing a bioactive agent,

forming a conjugate of the bioactive agent and poly[N-(2-hydroxypropyl)methacrylamide-co-methoxyethyl methacrylate] copolymer, and forming a coating comprising the conjugate on the implantable device.

13. The method of claim 12, wherein the conjugate comprises covalent bonding between the bioactive agent and the copolymer.

14. The method of claim 13, wherein the conjugate further comprises a linker.

15. The method of claim 13, wherein the conjugate further comprises poly(ethylene glycol) (PEG), an alkyl chain, or a peptide sequence.

16. The method of claim 15, wherein the peptide sequence comprises glycine-phenylalinine-leucine-glycine.