USRE49528EActiveUtility
Bioactive coatings
Est. expiryApr 26, 2033(~6.8 yrs left)· nominal 20-yr term from priority
A61L 2400/10A61L 2300/42A61L 2300/236A61L 2300/208A61L 2300/206A61L 33/064A61L 33/0029A61L 33/0011A61L 31/10A61L 29/085A61L 27/34A61L 31/16A61L 27/54A61L 2300/404A61L 29/16A61K 31/728A61L 31/041A61L 29/049A61K 9/0012A61K 47/32A61K 31/131A61K 31/727A61L 27/26A61L 2300/45A61L 31/048A61L 2300/44A61K 31/14A61L 27/16A61L 29/041
63
PatentIndex Score
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Cited by
87
References
49
Claims
Abstract
Antimicrobial and antithrombogenic polymer or polymeric blend, compounds, coatings, and materials containing the same, as well as articles made with, or coated with the same, and methods of making the same exhibiting improved antimicrobial properties and reduced platelet adhesion. Embodiments include polymers with antimicrobial and antithrombogenic groups bound to a single polymer backbone, an antimicrobial polymer blended with an antithrombogenic polymer, and medical devices coated with the antimicrobial and antithrombogenic polymer or polymeric blend.
Claims
exact text as granted — not AI-modifiedThe invention claimed is:
1. A compound comprising
a random polymer of:
(i) a heparin-poly(ethylene glycol) methacrylate monomer having a single heparin,
(ii) methoxy(polyethylene glycol) methacrylate monomer,
(iii) butyl methacrylate monomer and/or methacrylic acid monomer and/or benzoylphenyl methacrylate monomer; and
(iv) poly(hexanide)-poly(ethylene glycol) methacrylate monomer and/or poly(hexanide) methacrylate monomer,
with the polymer being free of crosslinks.
2. The compound of claim 1 wherein the heparin is a heparin derivative, a heparin sulfate, a heparan sulfate, a heparin salt, or a heparin amine.
3. The compound of claim 1 wherein a ratio of a number of the heparin to a number of the hexanide groups on the polymer is between about 1:3 and about 1:25.
4. The compound of claim 3 wherein the ratio is between about 1:6 and about 1:20.
5. The compound of claim 1 wherein a concentration of the heparin compared to the polymer is between about 1% and about 20% w/w.
6. The compound of claim 5 wherein the concentration of the heparin compared to the polymer is between about 1.5% and about 8% w/w.
7. The compound of claim 1 wherein a concentration of the poly(hexanide) group compared to the compound is between about 2% and about 10% w/w.
8. The compound of claim 7 wherein the concentration of the poly(hexanide) group compared to the com pound is between about 6% and about 8% w/w.
9. The compound of claim 1 further comprising a lubricant group and/or an anti-fouling group covalently bound to the polymer.
10. The compound of claim 1 wherein a number of CH 2 CH 2 O repeats in the heparin-poly(ethylene glycol) methacrylate monomer, methoxy(polyethylene glycol) methacrylate monomer, and the poly(hexanide)-poly(ethylene glycol) methacrylate monomer is independently selected to be from 1 to 50.
11. A polymeric coating comprising the compound of claim 1 blended with a lubricant and/or an anti-fouling compound.
12. The polymeric coating of claim 11 wherein the lubricant comprises an N-vinyl pyrrolidone group and/or a glycerol methacrylate group.
13. The polymeric coating of claim 11 wherein the anti-fouling compound is methacryloyloxyethyl phosphorylcholine, 2-((2-(methacryloyloxy)ethyl)dimethylammonio)ethyl 2-methoxyethyl phosphate, 2-((2-(methacryloyloxy)ethyl)dimethylammonio)propyl 2-methoxyethyl phosphate, or combinations thereof.
14. A medical device comprising a coating that comprises the compound of claim 1 .
15. The medical device of claim 14 wherein the polymeric coating further comprises a lubricant agent and/or an anti-fouling functional agent.
16. The medical device of claim 15 wherein the lubricant agent is covalently bound to the polymer.
17. The medical device of claim 15 wherein the lubricant agent comprises an N-vinyl pyrrolidone group and/or a glycerol methacrylate group.
18. The medical device of claim 15 wherein the anti-fouling agent is covalently bound to the polymer.
19. The medical device of claim 15 wherein the anti-fouling agent is methacryloyloxyethyl phosphorylcholine, 2-((2-(methacryloyloxy)ethyl)dimethylammonio)ethyl 2-methoxyethyl phosphate, 2-((2-(methlacryloyloxy)ethyl) dimethylammonio)proply 2-methoxyethyl phosphate, or combinations thereof.
20. The medical device of claim 14 further comprising an artificial blood vessel, a cardiac stent, a venous stent, an arterial stent, a kidney stent, a ureter stent, a valve, a cardiac valve leaflet, a shunt, a cardiac device, a pacemaker, a transcutaneous catheter, a dialysis port, or a port for chemotherapy.
21. A method for making a polymer, the method comprising:
polymerizing a mixture of:
(i) heparin-poly(ethylene glycol) methacrylate monomer having a single heparin,
(ii) methoxy(polyethylene glycol) methacrylate monomer,
(iii) butylmethacrylate monomer and/or methacrylic acid monomer and/or benzovlphenyl methacrylate monomer; and
(iv) poly(hexanide)-poly(ethylene glycol) methacrylate monomer and/or poly(hexanide) methacrylate monomer,
with the polymer being made without crosslinks.
22. The method of claim 21 further comprising adding a free radical initiator to the mixture.
23. The method of claim 21 wherein the polymerizing step is performed between about 60° C. and about 80° C.
24. The method of claim 21 wherein the polymerizing step is terminated after no more than about 90 minutes.
25. The method of claim 21 wherein the polymerizing step is terminated after at least 20 minutes has passed.
26. The method of claim 21 wherein the ratio of a number of the heparin to a number of the hexanide groups on the polymer is between about 1:3 and about 1:25.
27. The method of claim 26 wherein the ratio is between about 1:6 and about 1:20.
28. An anti-microbial polymer which is a copolymer of
(a) an anti-microbial monomer consisting of a polymerizable group that is connected to a guanide or biguanide antimicrobial agent by a polyethylene oxide attachment group; and (b) one or more co-monomers selected from acrylates, methacrylates, (meth)acrylic acid, 2-hydroxyethyl methacrylate, hydroxypropyl methacrylate, n-butyl methacrylate, tert-butyl methacrylate, n-hexyl methacrylate, 2-methoxyethyl methacrylate, and monomers comprising poly(ethylene glycol); wherein said polymer is free of antithrombogenic agents.
29. The anti-microbial polymer of claim 28, wherein the polymerizable group is a methacrylate group or an acrylate group.
30. The anti-microbial polymer of claim 28, wherein the antimicrobial agent is a poly(hexamethylene biguanide) (PHMB) group, a poly(hexamethylene guanidine) (PHMG) group or a chlorhexidine group.
31. The anti-microbial polymer of claim 28, wherein the anti-microbial monomer has the molecular structure:
where n is from 1 to 30, m is from 1 to 10, p is from 1 to 10,000, and X is methyl or hydrogen.
32. The anti-microbial polymer of claim 31, wherein n is from 5 to 15.
33. The anti-microbial polymer of claim 31, wherein m is from 3 to 6.
34. The anti-microbial polymer of claim 31, wherein m is 6.
35. The anti-microbial polymer of claim 31, wherein p is from 5 to 50.
36. The anti-microbial polymer of claim 31, wherein X is methyl.
37. The anti-microbial polymer of claim 28, wherein the anti-microbial monomer is poly(ethylene glycol) methacrylate poly(hexamethylene guanide) (PEGMA-PHMG) or poly(ethylene glycol) methacrylate poly(hexamethylene biguanide) (PEGMA-PHMB).
38. The anti-microbial polymer of claim 28, wherein the one or more co-monomers include poly(ethylene glycol) (meth)acrylate monomers, including methoxy poly(ethylene) glycol (meth)acrylate monomers.
39. The anti-microbial polymer of claim 28, wherein the one or more co-monomers include methacrylic acid and/or benzoylphenyl methacrylate and/or butyl methacrylate.
40. The anti-microbial polymer of claim 28, which is a copolymer of:
(a) poly(ethylene glycol) methacrylate poly(hexamethylene guanide) (PEGMA-PHMG) or poly(ethylene glycol) methacrylate poly(hexamethylene biguanide) (PEGMA-PHMB) and (b) co-monomers of methoxy poly(ethylene glycol) (meth)acrylate, butyl methacrylate, and methacrylic acid and/or 4-benzoylphenyl methacrylate.
41. A polymeric coating comprising the anti-microbial polymer of claim 28.
42. A medical device which is coated with the anti-microbial polymer of claim 28.
43. The medical device of claim 42, wherein the medical device is selected from a contact lens or intra-ocular lens, a catheter for vascular access (arterial and/or venous), abdominal cavity tubing, a drainage bag and/or a connector, a catheter, a blood bag, a dialysis or other membrane, surgical gloves, a surgical instrument, a vascular graft, a stent, a contact lens case, a bottle, diagnostic apparatus, an oxygenator, a heart valve and/or pump, artificial blood vessels, a cardiac stent, a venous stent, an arterial stent, a kidney stent, a ureter stent, a valve, a cardiac valve leaflet, a shunt, a cardiac device, a pacemaker, a transcutaneous catheter, a dialysis port or a port for chemotherapy.
44. A method for making an anti-microbial polymer as claimed in claim 28, comprising the steps of mixing the anti-microbial monomer with the one or more co-monomers, degassing the mixture, heating the mixture to the reaction temperature, and adding a polymerization initiator.
45. The method of claim 44, wherein the reaction temperature is between about 60° C. and about 80° C.
46. A method for reducing the susceptibility of a substrate to platelet adhesion, comprising the step of coating the substrate with an anti-microbial polymer as claimed in claim 28.
47. The method of claim 46, wherein the substrate is a medical device.
48. Use of an anti-microbial polymer as claimed in claim 28 for reducing platelet adhesion to a substrate.
49. Use according to claim 48, wherein the substrate is a medical device.Cited by (0)
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