Crosslinked mixed charge hydrogels

Patent metadata

Field	Value
Publication number	US-9738780-B2
Application number	US-201615211278-A
Country	US
Kind code	B2
Filing date	Jul 15, 2016
Priority date	Nov 6, 2009
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

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 invention claimed is:

1. A crosslinked hydrogel, comprising:
a crosslinked polymer having repeating units comprising a plurality of positively charged repeating units and a plurality of negatively charged repeating units, wherein the crosslinked ratio of the number of positively charged repeating units to the number of the negatively charged repeating units is from about 1:1.1 to about 1:0.5; 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, or PO;
x is an integer from about 5 to about 10,000;
X − is a counter ion associated with the N + cationic center; and
M + is a counter ion associated with the (A=O)O − anionic center.

2. The crosslinked hydrogel of claim 1 , wherein each repeating unit is represented by the formula:

wherein
R 7 and R 8 are independently selected from hydrogen, fluorine, trifluoromethyl, C1-C6 alkyl, and C6-C12 aryl groups;
R 9 , R 10 , and R 11 are independently selected from alkyl and aryl, or taken together with the nitrogen to which they are attached form a cationic center;
A 3 (=O)—OM) is an anionic center, wherein A 3 is C, S, SO, or PO, and M is a metal or organic counterion;
L 6 is a linker that covalently couples the cationic center [N + (R 9 )(R 10 )(R 11 )] to the polymer backbone;
L 7 is a linker that covalently couples the anionic center [A 3 (=O)—OM] to the polymer backbone;
X − is the counter ion associated with the cationic center [N+(R9)(R10)(R11)];
M + is a counter ion associated with the (A=O)O − anionic center;
n is an integer from 5 to about 10,000; and
p is an integer from 5 to about 10,000.

3. The hydrogel of claim 2 , wherein R 1 , R 2 , R 3 , R 7 , R 8 , R 9 , R 10 , and R 11 are independently selected from the group consisting of C1-C3 alkyl.

4. The hydrogel of claim 2 , wherein R 7 , R 8 , R 9 , R 10 , and R 11 are methyl.

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

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

7. The hydrogel of claim 2 , wherein L 6 is 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 1-20.

8. The hydrogel of claim 2 , wherein L 7 is a C1-C20 alkylene chain.

9. The hydrogel of claim 2 , wherein L 6 and L 7 are —C(═O)O—(CH 2 ) 2 —.

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

11. The hydrogel of claim 2 , wherein M + at each occurrence is selected from the group consisting of a metal and organic ion.

12. The hydrogel of claim 2 , 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.

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

14. The hydrogel of claim 2 , wherein n is an integer from about 10 to about 1,000.

15. The hydrogel of claim 2 , wherein p is an integer from about 10 to about 1,000.

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

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

18. The hydrogel of claim 17 , wherein the particle is a nanoparticle.

19. The hydrogel of claim 18 , wherein the nanoparticle has a diameter of about 5 nm to about 200 nm.

20. The hydrogel of claim 18 , wherein the nanoparticle is a gold nanoparticle.

21. The hydrogel of claim 18 , wherein the nanoparticle is a polymer-coated nanoparticle.

22. The hydrogel of claim 21 , wherein the nanoparticle is coated with a polymer comprising carboxybetaine methacrylate (CBMA) or oligo(ethylene glycol) methyl ether methacrylate (OEGMA).

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

24. The surface of claim 23 , wherein the substrate is selected from the group consisting of a medical device, a glucose sensor, a particle, a drug carrier, a non-viral gene delivery system, a biosensor, a membrane, an implantable sensor, a subcutaneous sensor, an implant, and a contact lens.

25. The surface of claim 24 , wherein the particle is a nanoparticle.

Assignees

• Univ Washington Through Its Center For Commercialization

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

• A61L31/145

  Hydrogels or hydrocolloids · CPC title

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• C12Y101/03004

  Glucose oxidase (1.1.3.4) · CPC title

• C12Q1/54

  involving glucose or galactose · CPC title