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

• US 10,363,340 B2
• Filed: 11/04/2015
• Issued: 07/30/2019
• Est. Priority Date: 11/04/2014
• Status: Active Grant

• Current Assignee: Mcmaster University
• Original Assignee: Mcmaster University
• Inventors: Hoare, Todd, Bakaic, Emilia, Smeets, Niels M. B., Deng, Xudong
• Primary Examiner(s): Godenschwager, Peter F
• Application Number:
  US14/932,444
• Publication Number:
  US 20160151535A1
• Time in Patent Office: 1,364 Days
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 26/0052 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61M 5/19 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 Class Codes: C08L 71/02 Polyalkylene oxides

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.

Claims

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)

9. The hydrogel composition of claim 8, wherein

R¹ is H or (C₁-C₄)alkyl, and

R² is H, (C₁-C₄)alkyl, —

(C₀-C₂)-alkylene-phenyl, or —

C(O)O—

R′

, wherein R′

is H or (C₁-C₄)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)

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)

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)

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.