Process and systems for biocompatible surfaces
View Patent ↗The invention provides methods and compositions for providing biocompatible surfaces to medical articles. In particular the invention provides biocompatible coatings with heparin activity that are able to release a bioactive agent, wherein the coatings are formed using biostable or biodegradable polymeric material and photoreactive groups.
1. A medical article having a bioactive agent-releasing coating having heparin activity of 10 mU/cm 2 or greater, the coating comprising:
(a) a first coated layer comprising bio-stable or biodegradable polymer and bioactive agent; and
(b) a second coated layer comprising heparin and photoreactive groups.
2. The medical article of claim 1 wherein the bioactive agent-releasing coating has heparin activity of 20 mU/cm 2 or greater.
3. The medical article of claim 1 wherein the bioactive agent is selected from macrolide antibiotics, immunomodulatory agents, and anti-mitotics.
4. The medical article of claim 2 wherein the macrolide antibiotic is selected from the group of consisting of rapamycin, tacrolimus, ABT-578, and everolimus.
5. The medical article of claim 1 comprising a bio-stable polymer that is a vinyl polymer.
6. The medical article of claim 5 wherein the vinyl polymer is an ethylene vinyl alcohol copolymer.
7. The medical article of claim 1 comprising a biodegradable polymer that is selected from polylactic acid, polyglycolic acid, and copolymers thereof.
8. The medical article of claim 1 wherein heparin comprises pendent photoreactive groups.
9. The medical article of claim 1 further comprising a component selected from the group of non-water soluble crosslinking agents, vinylpyrrolidone polymers, polyethylene glycol, polyethylene glycol sulfonates, fatty quatemary amines, fatty sulfonates, fatty acids, dextran, dextran, dextrin, and cyclodextrin, the component having pendent photo-reactive groups.
10. The medical article of claim 9 wherein the component comprises vinylpyrrolidone polymers having pendent photoreactive groups.
11. The medical article of claim 9 wherein the component comprises a non-water soluble crosslinking agent having two or more pendent photoreactive groups.
12. The medical article of claim 1 being an intraluminal prosthesis.
13. The medical article of claim 12 being a stent.
14. A medical article having a coating with heparin activity, the coating comprising:
(a) a first coated layer comprising polymer and bioactive agent, wherein the bioactive agent maximally absorbs light at a wavelength of below 300 nm; and
(b) a second coated layer comprising heparin and photoreactive groups, wherein the photoreactive groups maximally absorb light at a wavelength of 320 nm or above, wherein the second coated layer is formed by applying irradiation through a filter in an amount in the range of 0.12 J/cm2 to 0.96 J/cm2 as measured at 335 nm, and wherein the filter is selected from the group consisting of from ultra-violet cut-off filters, ultra-violet transmitting filters, band pass filters, and colored filters.
15. A medical article having a coating with heparin activity, the coating comprising:
(a) a first coated layer comprising a polymer selected from vinyl polymers, and a bioactive agent; and
(b) a second coated layer comprising heparin and photoreactive groups.
16. A medical article having a biodegradable coating with heparin activity, the coating comprising:
(a) biodegradable polymer;
(b) bioactive agent;
(c) heparin having pendent photo-reactive groups; and
(d) a component selected from the group of non-water soluble crosslinking agents, vinylpyrrolidone polymers, polyethylene glycol, polyethylene glycol sulfonates, fatty quatemary amines, fatty sulfonates, fatty acids, dextran, dextrin, and cyclodextrin, the component having pendent photo-reactive groups.
17. The medical article of claim 1 wherein the bio-stable or biodegradable polymer is soluble in chloroform.