In situ gelling zwitterionic hydrogel compositions, and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12359026-B2
Application number	US-202117927817-A
Country	US
Kind code	B2
Filing date	May 28, 2021
Priority date	May 28, 2020
Publication date	Jul 15, 2025
Grant date	Jul 15, 2025

Abstract

The disclosure relates to an in situ-gelling hydrogel composition based on functionalized zwitterionic polymers. The resulting hydrogels exhibit highly anti-fouling, anti-adhesive, and lubricating properties to enable the fabrication of bulk hydrogels or hydrogel-based coatings of relevance to biomedical applications.

First claim

The invention claimed is:

1. A hydrogel composition, comprising
a. at least one first polymer comprising monomeric units of
i. one or more first polymerizable ethylenically unsaturated zwitterionic monomers containing at least one cationic charge and at least one anionic charge at neutral pH; and
ii. one or more polymerizable ethylenically unsaturated monomers functionalized with a nucleophilic moiety;

b. at least one second polymer comprising monomeric units of
i. one or more second polymerizable ethylenically unsaturated zwitterionic monomers containing at least one cationic charge and at least one anionic charge at neutral pH; and
ii. one or more polymerizable ethylenically unsaturated monomer functionalized with an electrophilic moiety, wherein the electrophilic moiety of at least one polymerizable ethylenically unsaturated monomer comprises a ketone group; and

wherein the first and second polymers are crosslinked through covalent bonds by reaction of the nucleophilic and electrophilic moieties to form the hydrogel composition.

2. The hydrogel composition of claim 1 , wherein the first and second zwitterionic moieties independently or simultaneously have the structure

wherein
X is O or NR′, wherein R′ is H or (C 1 -C 6 )-alkyl;
R 1 is H, (C 1 -C 10 )-alkyl, OH, or —O—(CH 2 ) x where x is an integer between 1 and 10;
R 2 is a hydrocarbyl moiety containing an anionic moiety and a cationic moiety.

3. The hydrogel composition of claim 2 , wherein the first and second zwitterionic moieties independently or simultaneously have the structure

wherein
X is O or NR′, wherein R′ is H or (C 1 -C 6 )-alkyl;
R 1 is H, (C 1 -C 10 )-alkyl, OH, or —O—(CH 2 ) x where x is an integer between 1 and 10;
Y and Y′ are independently or simultaneously (C 1 -C 10 )-alkylene, optionally wherein one or more carbon atoms are replaced with oxygen atoms;
W is a cationic moiety or an anionic moiety; and
T is an anionic moiety or a cationic moiety,
wherein when W is a cationic moiety, T is an anionic moiety, and when W is an anionic moiety, T is a cationic moiety, and
wherein the net charge of the monomer is zero.

4. The hydrogel composition of claim 3 , wherein the cationic moiety is an amine or ammonium moiety.

5. The hydrogel composition of claim 4 , wherein the amine moiety is —NR′— and the ammonium moiety is —N + R′R″—, wherein R′ and R″ are independently or simultaneously H or (C 1 -C 6 )-alkyl.

6. The hydrogel composition of claim 3 , wherein the anionic moiety is a sulfate, carboxyl, phosphate, or boronate moiety.

7. The hydrogel composition of claim 3 , wherein the first and second zwitterionic monomers independently or simultaneously have the structure

wherein,
X is O or NR′, wherein R′ is H or (C 1 -C 6 )-alkyl
R 1 is H, (C 1 -C 10 )-alkyl, OH, or —O—(CH 2 ) x where x is an integer between 1 and 10;
R′ and R″ are independently or simultaneously H or (C 1 -C 6 )-alkyl; and
n is an integer from 1 to 10.

8. The hydrogel composition of claim 7 , wherein the first and second zwitterionic monomers have the structure

9. The hydrogel composition of claim 1 , wherein the polymerizable ethylenically unsaturated monomer functionalized with a nucleophilic moiety has the formula

wherein
X is O or NR′, wherein R′ is H or (C 1 -C 6 )-alkyl;
R 3 is H or (C 1 -C 6 )-alkyl;
M is (C 0 -C 3 )-alkylene; and
V is a hydrocarbyl moiety containing a nucleophilic moiety.

10. The hydrogel composition of claim 9 , wherein the polymerizable ethylenically unsaturated monomer functionalized with a nucleophilic moiety has the formula

wherein
X is O or NR′, wherein R′ is H or (C 1 -C 6 )-alkyl;
R 3 is H or (C 1 -C 6 )-alkyl; and
V is a hydrocarbyl moiety containing a nucleophilic moiety.

11. The hydrogel composition of claim 9 , wherein the polymerizable ethylenically unsaturated monomer functionalized with a nucleophilic moiety has the formula

wherein m is 1-10 and R 3 is H or (C 1 -C 6 )-alkyl.

12. The hydrogel composition of claim 10 , wherein the polymerizable ethylenically unsaturated monomer functionalized with a nucleophilic moiety has the formula

13. The hydrogel composition of claim 1 , wherein polymerizable ethylenically unsaturated monomer functionalized with an electrophilic moiety has the formula

wherein
X is O or NR′, wherein R′ is H or (C 1 -C 6 )-alkyl;
Ra is H or —COOH;
R 3 is H or (C 1 -C 6 )-alkyl, wherein the (C 1 -C 6 )-alkyl group is optionally substituted with a —COOH group;
M is (C 0 -C 3 )-alkylene; and
V is a hydrocarbyl moiety containing at least one electrophilic moiety, wherein at least one electrophilic moiety comprises a ketone group.

14. The hydrogel composition of claim 13 , wherein polymerizable ethylenically unsaturated monomer functionalized with an electrophilic moiety has the formula

wherein
X is O or NR′, wherein R′ is H or (C 1 -C 6 )-alkyl;
Ra is H or —COOH;
R 3 is H or (C 1 -C 6 )-alkyl, wherein the (C 1 -C 6 )-alkyl group is optionally substituted with a —COOH group;
V is a hydrocarbyl moiety containing at least one electrophilic moiety.

15. The hydrogel composition of claim 13 , wherein the polymerizable ethylenically unsaturated monomer functionalized with an electrophilic moiety has the formula

wherein
R 3 is H or (C 1 -C 6 )-alkyl;
R 4 is H, (C 1 -C 10 )-alkyl, wherein one or more CH 2 groups in (C 1 -C 10 )-alkyl are optionally replaced with C═O;
v is an integer from between 1 and 10; and
wherein one or more carbon atoms in the group (CH 2 ) y are optionally replaced with oxygen atoms or nitrogen atoms (NH or NR′ wherein R′ is C 1 -C 6 -alkyl).

16. The hydrogel composition of claim 15 , wherein the polymerizable ethylenically unsaturated monomer functionalized with an electrophilic moiety has the formula

17. The hydrogel composition of claim 1 , wherein the nucleophilic moiety is a hydrazide or amine derivative, a carbonyl hydrate, an alcohol, cyanohydrin or cyanohydrin derivative, a thiol or thiol derivative, or a phosphorus

Assignees

• McMaster Unversity
• Univ Mcmaster

Inventors

• Hoare Todd
• Dorogin Jonathan
• Pan Zhicheng
• Preciado Rivera Nahieli Iyeida

Classifications

• C08L33/26

  Homopolymers or copolymers of acrylamide or methacrylamide · CPC title

• C08J2333/26

  Homopolymers or copolymers of acrylamide or methacrylamide · CPC title

• C08J3/246 Primary

  Intercrosslinking of at least two polymers · CPC title

• A61L2430/24

  for joint reconstruction · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title