# US 11,998,657 B2 · Biodegradable, thermally responsive injectable hydrogel for treatment of ischemic cardiomyopathy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,998,657 B2 - Document ID: US11998657B2 - Status: Granted - Kind: B2 - Application number: 17/394,984 - Filed: 2021-08-05 - Published: 2021-11-25 - Granted: 2024-06-04 - Earliest claimed: 2014-04-14 - Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education - Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education - Inventors: Hongbin Jiang; William R. Wagner; Tomo Yoshizumi; Yang Zhu - Web page: https://patentgrep.com/patent/US11998657B2 ## CPC - A61L 27/16: obtained by reactions only involving carbon-to-carbon unsaturated bonds - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61L 27/52: Hydrogels or hydrocolloids - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - C08F 220/54: Amides {, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide} - A61K 47/30: Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates - A61L 2300/414: Growth factors - A61L 2400/06: Flowable or injectable implant compositions - A61L 2430/20: for reconstruction of the heart, e.g. heart valves - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS ## Abstract Provided are novel biocompatible copolymers, compositions comprising the copolymers, and methods of using the copolymers. The copolymers are non-toxic and typically have an LCST below 37° C. Compositions comprising the copolymers can be used for wound treatment, as a cellular growth matrix or niche and for injection into cardiac tissue to repair and mechanically support damaged tissue. The copolymers comprise numerous ester linkages so that the copolymers are erodible in situ. Degradation products of the copolymers are soluble and non-toxic. The copolymers can be amine-reactive so that they can conjugate with proteins, such as collagen. Active ingredients, such as drugs, can be incorporated into compositions comprising the copolymers. ## Claims ### Claim 1 A composition, comprising a copolymer having a lower critical solution temperature (LCST) of less than 37° C., comprising N-isopropyl acrylamide (NIPAAm); N-vinylpyrrolidone (VP) residues; and methacrylate-polylactide (MAPLA) macromer residues, the copolymer prepared by radical polymerization with a feed ratio of NIPAAm:VP:MAPLA in the range of 75-85:5-20:5-10; and has having a degradation rate of less than 200 days in vivo. ### Claim 2 (depends on 1) The composition of claim 1, wherein the copolymer is prepared by radical polymerization with a feed ratio of NIPAAm:VP:MAPLA in the range of 75-85:10:5-10. ### Claim 3 (depends on 1) The composition of claim 1, wherein the copolymer is prepared by radical polymerization with a feed ratio of NIPAAm:VP:MAPLA in the range of 75-85:15:5-10. ### Claim 4 (depends on 1) The composition of claim 1, wherein the copolymer comprises NIPAAm:VP:MAPLA in a ratio of 80:15:5. ### Claim 5 (depends on 1) The composition of claim 1, wherein the copolymer has a degradation rate of less than 90 days in vivo. ### Claim 6 A method of treating a myocardial defect in a patient comprising injecting into a site of the myocardial defect a composition comprising a copolymer having a lower critical solution temperature (LCST) of less than 37° C., comprising N-isopropyl acrylamide (NIPAAm); N-vinylpyrrolidone (VP) residues; and methacrylate-polylactide (MAPLA) macromer residues, wherein the copolymer is prepared by radical polymerization with a feed ratio of NIPAAm:VP:MAPLA in the range of 75-85:5-20:5-10 and has a degradation rate of less than 200 days in vivo, wherein the myocardial defect is a site of tissue injury in the myocardium. ### Claim 7 (depends on 6) The method of claim 6, wherein the defect is an infarct or a traumatic injury, and the copolymer composition is injected into, in contact with and/or in tissue surrounding the infarct or traumatic injury. ### Claim 8 (depends on 6) The method of claim 6, wherein the defect is an infarct or a traumatic injury, and the copolymer composition is injected into, in contact with and/or in tissue surrounding the infarct or traumatic injury between 1 and 21 days after a myocardial infarction or myocardial injury. ### Claim 9 (depends on 6) The method of claim 6, wherein the defect is an infarct or a traumatic injury, and the copolymer composition is injected into, in contact with and/or in tissue surrounding the infarct or traumatic injury between 7 and 14 days after a myocardial infarction or myocardial injury. ### Claim 10 (depends on 6) The method of claim 6, wherein the composition has a degradation rate of less than 90 days in vivo. ### Claim 11 (depends on 6) The method of claim 6, wherein the copolymer is prepared by radical polymerization with a feed ratio of NIPAAm:VP:MAPLA in the range of 75-85:10:5-10. ### Claim 12 (depends on 6) The method of claim 6, wherein the copolymer is prepared by radical polymerization with a feed ratio of NIPAAm:VP:MAPLA in the range of 75-85:15:5-10.