Non-fouling, anti-microbial, anti-thrombogenic graft—from compositions

Patent metadata

Field	Value
Publication number	US-9895470-B2
Application number	US-63268609-A
Country	US
Kind code	B2
Filing date	Dec 7, 2009
Priority date	Dec 5, 2008
Publication date	Feb 20, 2018
Grant date	Feb 20, 2018

Abstract

Substrates, optionally coated with an undercoating layer, having grafted there from one or more non-fouling materials are described herein. The non-fouling, polymeric material can be grafted from a variety of substrate materials, particularly polymeric substrates and/or polymeric undercoating layers. The graft-from techniques described herein can result in higher surface densities of the non-fouling material relative to graft-to formulations. Graft-from methods can be used to produce covalently tethered polymers. The compositions described herein are highly resistant protein absorption, particularly in complex media and retain a high degree of non-fouling activity over long periods of time. The compositions described herein may also demonstrate antimicrobial and/or anti-thrombogenic activity. The non-fouling material can be grafted from the substrate, or optionally from an undercoating layer on the substrate, preferably without significantly affecting the mechanical and/or physical properties of the substrate material.

First claim

We claim:

1. A method of making a composition comprising a substrate, a non-fouling polymeric material, and optionally an undercoating layer immobilized on the substrate, the non-fouling polymeric material being covalently bound to the substrate or the undercoating layer, the method comprising imbibing one or more initiators into the substrate or the undercoating layer and grafting the non-fouling polymeric material from the imbibed substrate or the undercoating layer, wherein the substrate is selected from the group consisting of metallic materials, wherein the metallic materials is selected from the group consisting of titanium and alloys thereof, stainless steel, tantalum, palladium, zirconium, niobium, molybdenum, nickel-chrome, cobalt or alloys thereof, and combinations thereof.

2. A method of making a composition comprising a substrate, a non-fouling polymeric material, and optionally an undercoating layer immobilized on the substrate, the non-fouling polymeric material being covalently bound to the substrate or the undercoating layer, the method comprising imbibing one or more initiators into the substrate or the undercoating layer and grafting the non-fouling polymeric material from the imbibed substrate or the undercoating layer, wherein the substrate is selected from the group consisting of ceramics, wherein the ceramic is selected from the group consisting of oxides, carbides, or nitrides of the transition metal elements or metalloid elements.

3. A method of making a composition comprising a substrate, a non-fouling polymeric material, and optionally an undercoating layer immobilized on the substrate, the non-fouling polymeric material being covalently bound to the substrate or the undercoating layer, the method comprising imbibing one or more initiators into the substrate or the undercoating layer and grafting the non-fouling polymeric material from the imbibed substrate or the undercoating layer, wherein the substrate is substantially thiol free.

4. A method of making a composition comprising a substrate, a non-fouling polymeric material, and optionally an undercoating layer immobilized on the substrate, the non-fouling polymeric material being covalently bound to the substrate or the undercoating layer, the method comprising imbibing one or more initiators into the substrate or the undercoating layer and grafting the non-fouling polymeric material from the imbibed substrate or the undercoating layer, wherein the non-fouling polymeric material is a zwitterionic polymer.

5. The method of claim 4 wherein the zwitterionic polymer is a homopolymer or copolymer comprising one more monomers having the following formula:

wherein B is selected from the group consisting of:

wherein R is selected from the group consisting of hydrogen, substituted alkyl, or unsubstituted alkyl;
E is selected from the group consisting of substituted alkyl, unsubstituted alkyl, —(CH 2 ) y C(O)O—, and —(CH 2 ) y C(O)NR 2 —;
R 2 is selected from hydrogen and substituted or unsubstituted alkyl;
Y is an integer from 0-12;
L is absent or is a straight or branched alkyl group optionally including one or more oxygen atoms;
ZI is a zwitterionic group; and
X is an integer from 3 to 1000.

6. The method of claim 5 , wherein ZI is selected from the group consisting of:

wherein
R 3 and R 4 are independently selected from the group consisting of hydrogen and substituted or unsubstituted alkyl;
R 5 is selected from the group consisting of substituted or unsubstituted alkyl, phenyl, and polyether groups; and
m is an integer from 1-7.

7. The method of claim 5 wherein x is from about 10 to about 500, from about 20 to about 250, or from about 30 to about 100.

8. The method of claim 5 , wherein the zwitterionic polymer is a homopolymer of sulfobetaine methacrylate (SBMA) or sulfobetaine acrylamide.

9. The method of claim 5 , wherein the zwitterionic polymer is a copolymer comprising sulfobetaine methacrylate (SBMA) or sulfobetaine acrylamide.

10. The method of claim 4 , wherein the zwitterionic polymer has the following structure:

wherein
B 1 and B 2 are independently selected from the group consisting of:

R is selected from the group consisting of hydrogen, substituted alkyl, or unsubstituted alkyl;
E is selected from substituted or unsubstituted alkylene, —(CH 2 ) p C(O)O—, and —(CH 2 ) p C(O)NR 2 —, wherein p is an integer from 0 to 12,
R 2 is selected from hydrogen and substituted or unsubstituted alkyl;
L is a straight or branched alkylene group optionally including one or more oxygen atoms;
P 1 is a positively charged group;
P 2 is a negative charged group;
m is an integer from 3 to 1000; and
n is an integer from 3 to 1000.

11. The method of claim 4 , wherein the polymer comprises one or more monomers selected from the group consisting of:

wherein
R is selected from and substituted or unsubstituted alkyl;
L 1 , L 2 , and L 3 are independently a straight or branched alkylene group optionally including one or more oxygen atoms; and
n is an integer from 3 to 1000; and
N 1 is a negatively charged group.

12. The method of claim 10 , wherein the negatively charged group is selected from the group consisting of carboxylate group, —SO 3 − , —OSO 3 − , —PO 3 − , and —OPO 3 − .

13. The method of claim 10 , wherein the positively charged group is a quaternized nitrogen or cationic phosphorous containing group.

14. The method of claim 10 , wherein x, m, and n are from about 10 to about 500, from about 20 to about 250, or from about 30 to about 100.

15. A method of making a composition comprising a substrate, a non-fouling polymeric material, and optionally an undercoating layer immobilized on the substrate, the non-fouling polymeric material being covalently bound to the substrate or the undercoating layer, the method comprising imbibing one or more initiators into the substrate or the undercoating layer and grafting the non-fouling polymeric material from the imbibed substrate or the undercoating layer, wherein the non-fouling material is a non-zwitterionic polymer selected from the group consisting of polyethers, polysaccharides, polyvinylpyrrolidone, hydroxyethylmethacrylate, acrylonitrile-acrylamide copolymers, heparin, mixed charge polymers, and polymers containing hydrogen bond accepting groups.

16. A method of making a composition comprising a substrate, a non-fouling polymeric material, and optionally an undercoating layer immobilized on the substrate, the non-fouling polymeric material being covalently bound to the substrate or the undercoating layer, the method comprising imbibing one or more initiators into the substrate or the undercoating layer and grafting the non-fouling polymeric material from the imbibed substrate or the undercoating layer, wherein the polymeric material is formed by UV-init

Assignees

• Li Jun
• Squier Trevor
• Zhang Zheng
• Huval Chad
• Oshaughnessy William Shannan
• Hencke Michael
• Bouchard Michael
• Loose Christopher R
• Semprus Biosciences Corp

Inventors

• Li Jun
• Squier Trevor
• Zhang Zheng
• Huval Chad
• Oshaughnessy William Shannan
• Hencke Michael
• Bouchard Michael
• Loose Christopher R

Classifications

• C09D151/003

  grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds (C09D151/04, C09D151/06 take precedence) · CPC title

• C09D151/085

  on to polysiloxanes · CPC title

• Y10T428/31663

  As siloxane, silicone or silane · CPC title

• C07H23/00

  Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00) · CPC title

• A61L31/10

  Macromolecular materials · CPC title