Crosslinked zwitterionic hydrogels

Patent metadata

Field	Value
Publication number	US-9394435-B2
Application number	US-201414457801-A
Country	US
Kind code	B2
Filing date	Aug 12, 2014
Priority date	Nov 6, 2009
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

Zwitterionic crosslinking agents, crosslinked zwitterionic hydrogels prepared from copolymerization of zwitterionic monomers with the zwitterionic crosslinking agent, methods for making crosslinked zwitterionic hydrogels, and devices that include and methods that use the crosslinked zwitterionic hydrogels.

First claim

The embodiments of the invention in which an exclusive property of privilege is claimed are defined as follows:

1. A crosslinked hydrogel, comprising a crosslinked polymer having repeating units and a plurality of crosslinks, wherein each crosslink is represented by the formula:

wherein
R 1 and R 2 are independently selected from the group consisting of hydrogen, fluorine, trifluoromethyl, C1-C6 alkyl, and C6-C12 aryl groups;
R 3 is selected from the group consisting of C1-C6 alkyl, C6-C12 aryl, CH 2 ═C(R 1 )-L 1 -, CH 2 ═C(R 2 )-L 2 -, or R 3 is the residual portion of a third crosslink, -L 1 -CR 1 —CH 2 — or -L 2 -CR 2 —CH 2 —;
L 1 and L 2 are independently selected from the group consisting of —C(═O)O—(CH 2 ) n — and —C(═O)NH—(CH 2 ) n —, wherein n is an integer from 1 to 20;
L 3 is —(CH 2 ) n —, where n is an integer from 1 to 20;
A 1 is C, S, SO, P, or PO;
x is an integer from about 5 to about 10,000;
X − is the counter ion associated with the N + cationic center; and
M + is a counterion associated with the (A=O)O − anionic center.

2. The hydrogel of claim 1 , wherein R 1 , R 2 , and R 3 are independently selected from the group consisting of C1-C3 alkyl.

3. The hydrogel of claim 1 , wherein L 1 and L 2 are —C(═O)O—(CH 2 ) n —, wherein n is 1-6.

4. The hydrogel of claim 1 , wherein L 3 is —(CH 2 ) n —, where n is an integer from 1-6.

5. The hydrogel of claim 1 , wherein A 1 is C or SO.

6. The hydrogel of claim 1 , wherein M + at each occurrence is a metal or organic ion.

7. The hydrogel of claim 1 , wherein X − at each occurrence is selected from the group consisting of halide, carboxylate, alkylsulfonate, sulfate, nitrate, perchlorate, tetrafluoroborate, hexafluorophosphate, trifluoromethylsulfonate, bis(trifluoromethylsulfonyl)amide, lactate, and salicylate.

8. The hydrogel of claim 1 , wherein x is an integer from about 10 to about 1,000.

9. The hydrogel of claim 1 , wherein the hydrogel is a gradient hydrogel.

10. A surface of a substrate, wherein the surface comprises a hydrogel of claim 1 .

11. The surface of claim 10 , wherein the substrate is selected from the group consisting of a medical device, a glucose sensor, a particle, a drug carrier, non-viral gene delivery system, a biosensor, a membrane, an implantable sensor, a subcutaneous sensor, an implant, and a contact lens.

12. The surface of claim 11 , wherein the particle is a nanoparticle.

13. The hydrogel of claim 1 , further comprising a particle encapsulated therein.

14. The hydrogel of claim 13 , wherein the particle is a nanoparticle.

15. The hydrogel of claim 14 , wherein the nanoparticle has a diameter of about 5 nm to about 200 nm.

16. The hydrogel of claim 14 , wherein the nanoparticle is a gold nanoparticle.

17. The hydrogel of claim 14 , wherein the nanoparticle is a polymer-coated nanoparticle.

18. The hydrogel of claim 17 , wherein the nanoparticle is coated with a polymer comprising carboxybetaine methacrylate (CBMA) or oligo(ethylene glycol) methyl ether methacrylate (OEGMA).

19. The hydrogel of claim 1 , wherein each repeating unit has the formula:

wherein
R 4 is selected from the group consisting of hydrogen, fluorine, trifluoromethyl, C1-C6 alkyl, and C6-C12 aryl groups;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, and aryl, or taken together with the nitrogen to which they are attached form a cationic center;
L 4 is a linker that covalently couples the cationic center [N + (R 5 )(R 6 )] to the polymer backbone [—(CH 2 —CR 4 ) n —];
L 5 is a linker that covalently couples the anionic center [A 2 (═O)—O − ] to the cationic center;
A 2 is C, S, SO, P, or PO;
M + is a counterion associated with the (A 2 =O)O − anionic center;
X − is a counter ion associated with the cationic center;
n is an integer from 5 to about 10,000.

20. The hydrogel of claim 19 , wherein R4, R5, and R6 are independently selected from the group consisting of C1-C3 alkyl.

21. The hydrogel of claim 19 , wherein L4 is selected from the group consisting of —C(═O)O—(CH2)n- and —C(═O)NH—(CH2)n-, wherein n is an integer from 1 to 20.

22. The hydrogel of claim 19 , wherein L5 is —(CH2)n-, where n is an integer from 1 to 20.

23. The hydrogel of claim 19 , wherein n is an integer from 10 to about 1,000.

24. The hydrogel of claim 19 , wherein M+ at each occurrence is a metal or organic ion.

25. The hydrogel of claim 19 , wherein X— at each occurrence is selected from the group consisting of halide, carboxylate, alkylsulfonate, sulfate, nitrate, perchlorate, tetrafluoroborate, hexafluorophosphate, trifluoromethylsulfonate, bis(trifluoromethylsulfonyl)amide, lactate, and salicylate.

Assignees

• Univ Washington Ct Commerciali

Inventors

• Jiang Shaoyi
• Xue Hong
• Yang Wei
• Carr Louisa R

Classifications

• A61K41/17

  by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays · CPC title

• C08F26/02

  by a single or double bond to nitrogen · CPC title

• C12Y101/03004

  Glucose oxidase (1.1.3.4) · CPC title

• G01N2333/904

  acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1) · CPC title

• Y10T428/31786

  Of polyester [e.g., alkyd, etc.] · CPC title