Poly(oligoethylene glycol methacrylate) hydrogel compositions, and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10363340-B2
Application number	US-201514932444-A
Country	US
Kind code	B2
Filing date	Nov 4, 2015
Priority date	Nov 4, 2014
Publication date	Jul 30, 2019
Grant date	Jul 30, 2019

Abstract

The present application relates to hydrogel compositions comprising first and second precursor polymers, wherein the precursor polymers are modified poly(oligoethylene glycol methacrylate) copolymers that are crosslinked through electrophile-nucleophile reactions.

First claim

The invention claimed is:

1. A hydrogel composition, comprising
a. at least one first precursor polymer which is a nucleophile-functionalized poly(oligoethylene glycol methacrylate) copolymer, and
b. at least one second precursor polymer which is an electrophile-functionalized poly(oligoethylene glycol methacrylate) copolymer,
wherein the first and second precursor polymers are crosslinked through covalent bonds by reaction of the nucleophilic and electrophilic moieties.

2. The hydrogel composition of claim 1 , wherein the nucleophile-functionalized poly(oligoethylene glycol methacrylate) copolymer comprises a nucleophilic moiety which is a hydrazide or amine derivative, a carbonyl hydrate, an alcohol, cyanohydrin or cyanohydrin derivative, a thiol or thiol derivative, or a phosphorus ylide or derivatives thereof.

3. The hydrogel composition of claim 2 , wherein the nucleophilic moiety is a hydrazide moiety.

4. The hydrogel composition of claim 1 , wherein the electrophile-functionalized poly(oligoethylene glycol methacrylate) polymer comprises an electrophilic moiety which is an aldehyde, a ketone, a carboxylic acid, an ester, an amide, a maleimide, an acyl (acid) chloride, an acid anhydride or an alkene group or derivatives thereof.

5. The hydrogel composition of claim 4 , wherein the electrophilic moiety is an aldehyde or ketone moiety.

6. The hydrogel composition of claim 1 , wherein the composition comprises
a. at least one first precursor polymer which is a hydrazide-functionalized poly(oligoethylene glycol methacrylate) copolymer, and
b. at least one second precursor polymer which is an aldehyde- and/or ketone-functionalized poly(oligoethylene glycol methacrylate) copolymer,
wherein the first and second precursor polymers are crosslinked through hydrazone bonds.

7. The hydrogel composition of claim 6 , wherein the first precursor polymer is a copolymer comprising monomeric units of:
a. a first monomer which is oligoethylene glycol methacrylate, or a derivative thereof; and
b. at least a second polymerizable monomer which is functionalized or is capable of being functionalized with a hydrazide moiety.

8. The hydrogel composition of claim 7 , wherein the first monomer has the structure of the formula (I)

wherein
R 1 is H, (C 1 -C 10 )alkyl or (C 2 -C 10 )alkynyl;
R 2 is H, (C 1 -C 10 )alkyl, (C 2 -C 10 )alkynyl, —(C 0 -C 4 )-alkylene-(C 6 -C 10 )aryl, —(C 0 -C 4 )-alkylene-(C 5 -C 10 )heteroaryl, —C(O)NR′ or —C(O)OR′, wherein R′ is H or (C 1 -C 6 )alkyl, and
n is any integer between 6 and 30.

9. The hydrogel composition of claim 8 , wherein
R 1 is H or (C 1 -C 4 )alkyl, and
R 2 is H, (C 1 -C 4 )alkyl, —(C 0 -C 2 )-alkylene-phenyl, or —C(O)O—R′, wherein R′ is H or (C 1 -C 4 )alkyl.

10. The hydrogel composition of claim 7 , wherein the second polymerizable monomer has a carboxylic acid moiety.

11. The hydrogel composition of claim 10 , wherein the second polymerizable monomer is acrylic acid or a derivative thereof, methacrylic acid, itaconic acid, fumaric acid, maleic acid, or vinylacetic acid.

12. The hydrogel composition of claim 7 , further comprising one or more monomers which are methacrylic acid, itaconic acid, fumaric acid, maleic acid, vinylacetic acid or tert-butyl-2-acryloylhydrazinecarboxylate (BAHC), 2-dimethylaminoethylmethacrylate (DMAEMA), 2-dimethylaminoethyacrylate (DMAEA), aminoethyl methacrylate (AEMA), allylamine, or derivatives of any of the above,
or which has the structure of the formula (II)

wherein
R 1 and R 2 are as defined in claim 8 , and
m is any integer between 2-5.

13. The hydrogel composition of claim 6 , wherein second precursor polymer is a copolymer comprising monomeric units of:
a. a first monomer which is oligoethylene glycol methacrylate, or a derivative thereof; and
b. at least one second polymerizable monomer which can be functionalized with a aldehyde moiety or a ketone moiety.

14. The hydrogel composition of claim 13 , wherein the first monomer has the structure of the formula (I)

wherein
R 1 is H, (C 1 -C 10 )alkyl or (C 2 -C 10 )alkynyl;
R 2 is H, (C 1 -C 10 )alkyl, (C 2 -C 10 )alkynyl, —(C 0 -C 4 )-alkylene-(C 6 -C 10 )aryl, —(C 0 -C 4 )-alkylene-(C 5 -C 10 )heteroaryl, —C(O)NR′ or —C(O)OR′, wherein R′ is H or (C 1 -C 6 )alkyl, and
n is any integer between 6 and 30.

15. The hydrogel composition of claim 13 , wherein the second polymerizable monomer is functionalized with an acetal moiety or a ketal moiety.

16. The hydrogel composition of claim 13 , wherein the second polymerizable monomer is N-(2,2-dimethoxyethyl)methacrylamide (DMEMAm) or (N-((2-methyl-1,3-dioxolan-2-yl)methyl)methacrylamide).

17. The hydrogel composition of claim 14 , further comprising one or more monomers which are acrylic acid, methacrylic acid, itaconic acid, fumaric acid, maleic acid, vinylacetic acid or tert-butyl-2-acryloylhydrazinecarboxylate (BAHC), -dimethylaminoethyacrylate (DMAEA), aminoethyl methacrylate (AEMA), allylamine, or derivatives of any of the above,
or which has the structure of the formula (II)

wherein
R 1 and R 2 are as defined in claim 8 , and
m is any integer between 2-5.

18. The hydrogel composition of claim 6 , wherein
a. the first precursor polymer is a co-polymer of at least oligoethylene glycol methacrylate and acrylic acid;
b. the second precursor polymer is a co-polymer of at least oligoethylene glycol methacrylate and N-(2,2-dimethoxyethyl)methacrylamide (DMEMAm),

wherein acrylic acid has carboxylic acid groups which are functionalized as hydrazide moieties, and DMEMAm has acetal groups which are functionalized as aldehyde moieties, and hydrazone bonds form between the hydrazide and aldehyde moieties.

19. A method for coating a substrate with a hydrogel composition, the method comprising,
a. adsorbing or reacting a first or second precursor polymer as defined in claim 1 on the substrate;
b. coating the substrate from step (a) with the alternate precursor polymer;
c. optionally repeating steps (a) and (b),
wherein the hydrogel composition as defined in claim 1 is formed on the substrate.

Assignees

• Univ Mcmaster

Inventors

• Hoare Todd
• Bakaic Emilia
• Smeets Niels M B
• Deng Xudong

Classifications

• A61M5/19

  having more than one chamber {, e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly (surgical glue applicators A61B17/00491)} · CPC title

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61L26/008

  Hydrogels or hydrocolloids · CPC title

• A61L24/043

  Mixtures of macromolecular materials · CPC title

• A61L26/0052 Primary

  Mixtures of macromolecular compounds · CPC title