# US 10,369,227 B2 · Immunocompatible polymers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,369,227 B2 - Document ID: US10369227B2 - Status: Granted - Kind: B2 - Application number: 14/252,137 - Filed: 2014-04-14 - Published: 2014-10-16 - Granted: 2019-08-06 - Earliest claimed: 2013-04-12 - Assignees: McMaster University - Applicants: McMaster University - Inventors: Harald Stover; Nicholas Burke - Web page: https://patentgrep.com/patent/US10369227B2 ## CPC - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract A polymer matrix is provided comprising an amine-containing polyampholyte covalently crosslinked with an electrophilic polymer to yield an immunocompatible polymer matrix. A hydrogel system incorporating the polymer matrix is also provided. ## Claims ### Claim 1 A biocompatible cross-linked polymer matrix encapsulating live cells, said matrix comprising a primary amine-containing polyampholyte covalently cross-linked with an electrophilic polymer or a small molecule crosslinking agent that is reactive to covalently crosslink primary amine groups within the polyampholyte to result in a matrix comprising live cells and having a net neutral or anionic charge, wherein the polyampholyte lacks cationic charge dense patches because it is prepared by copolymerization of cationic primary amine-containing monomers with anionic monomers, or by modifying negatively charged monomer units in a polyanion to positively charged monomer units, or by modifying positively charged monomer units in a polycation to negatively charged monomer units, to yield a polyampholyte comprising both negatively and positively charged monomer units. ### Claim 2 (depends on 1) The polymer matrix as defined in claim 1, wherein the polyampholyte comprises monomers that yield a primary amine group selected from the group consisting of N-(3-aminopropyl)methacrylamide, N-(2-aminoethyl)methacrylamide, N-(2-aminoethyl)-acrylamide, 2-aminoethyl methacrylate, 2-aminoethyl acrylate, vinylacetamide, vinylformamide, allylamine and vinylamine. ### Claim 3 (depends on 1) The polymer matrix as defined in claim 1, wherein the polyampholyte additionally comprises an uncharged hydrophilic monomer. ### Claim 4 (depends on 3) The polymer matrix as defined in claim 3, wherein the uncharged hydrophilic monomer is selected from the group consisting of 2-hydroxyethyl methacrylate, N-(2-hydroxypropyl)methacrylamide, N-(2-hydroxyethyl)acrylamide, methoxypolyethyleneglycol methacrylate, N,N-dimethylacrylamide and acrylamide. ### Claim 5 (depends on 1) The polymer matrix as defined in claim 1, wherein the electrophilic polymer comprises an electrophilic monomer content in the range of about 5-80 mol % of the matrix in combination with reactive neutral polar monomers or anionic monomers. ### Claim 6 (depends on 5) The polymer matrix as defined in claim 5, wherein neutral polar monomer is acrylamide, N,N-dimethylacrylamide, N-(2-hydroxyethyl)acrylamide or 2-methacryloyloxyethyl phosphorylcholine. ### Claim 7 (depends on 5) The polymer matrix as defined in claim 5, wherein the electrophilic monomer combines with an anionic monomer to form a polyanion selected from copolymers of maleic anhydride, cyclic anhydrides, linear anhydrides with a comonomer selected from an alkyl vinyl ether or an olefin, copolymers of azlactone with an acrylic comonomer and optionally a third neutral comonomer, N-(2-hydroxypropyl)methacrylamide, N-(2-hydroxyethyl)acrylamide, acrylamide, N,N-dimethylacrylamide, 2-methacryloyloxyethyl-phosphorylcholine, copolymers of N-acryloxysuccinimide, N-methacryloxysuccinimide or glycidyl methacrylate with anionic acrylate comonomers. ### Claim 8 (depends on 1) The polymer matrix as defined in claim 1, wherein the small molecule crosslinking agent is a phosphonium salt. ### Claim 9 (depends on 1) An immunocompatible hydrogel system comprising a cross-linked polymer matrix as defined in claim 1, wherein the cross-linked matrix surrounds or is dispersed within a hydrogel core. ### Claim 10 (depends on 9) The hydrogel system as defined in claim 9, wherein the hydrogel core comprises alginate, agarose or cellulose sulphate alone or together with alginate. ### Claim 11 (depends on 9) The hydrogel system as defined in claim 9, wherein the polyampholyte comprises monomers that yield a primary amine group selected from the group consisting of N-(3-aminopropyl)methacrylamide, N-(2-aminoethyl)methacrylamide, N-(2-aminoethyl)acrylamide, 2-aminoethyl methacrylate, 2-aminoethyl acrylate, vinylacetamide, vinylformamide, allylamine and vinylamine. ### Claim 12 (depends on 9) The hydrogel system as defined in claim 9, wherein the electrophilic polymer comprises an electrophilic monomer content in the range of about 5-80 mol % of the polymer in combination with a neutral polar monomer selected from acrylamide, N,N-dimethylacrylamide, N-(2-hydroxyethyl)acrylamide or 2-methacryloyloxyethyl phosphorylcholine, or the electrophilic monomer combines with an anionic monomer to form a polyanion selected from copolymers of maleic anhydrides, cyclic anhydrides, linear anhydrides with a comonomer selected from an alkyl vinyl ether or an olefin, copolymers of azlactone with acrylic acid or methacrylic acid and optionally a third neutral comonomer, N-(2-hydroxypropyl)methacrylamide, N-(2-hydroxyethyl)acrylamide, acrylamide, N,N-dimethylacrylamide, 2-methacryloyloxyethyl-phosphorylcholine, copolymers of N-acryloxysuccinimide, N-methacryloxysuccinimide or glycidyl methacrylate with acrylic acid or methacrylic acid. ### Claim 13 (depends on 1) The polymer matrix as defined in claim 1, wherein the polyampholyte comprises N-(3-aminopropyl)methacrylamide and methacrylic acid, and the electrophilic polymer is poly(methacrylic acid-co-4,4-dimethyl-2-vinyl-2-oxazoline-5-one). ### Claim 14 (depends on 1) The polymer matrix of claim 1, wherein said polyampholyte comprises a positively charged monomer and a negatively charged monomer or monomer that becomes negatively charged when ionized. ### Claim 15 (depends on 14) The polymer matrix of claim 14, wherein the negatively charged monomer, or monomer that becomes negatively charged when ionized, is selected from the group consisting of acrylic acid (AA), methacrylic acid (MAA), 2-carboxyethyl acrylate, vinylbenzoic acid, N-methacryloyl-glycine, N-methacryloyl-alanine, sulfonic acid-containing monomer and phosphonic acid-containing monomer. ### Claim 16 (depends on 14) The polymer matrix as defined in claim 14, wherein the negatively charged monomer comprises a combination of the negatively charged monomer with its acid form.