# US 8,541,013 B2 · Temperature and pH sensitive copolymers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,541,013 B2 - Document ID: US8541013B2 - Status: Granted - Kind: B2 - Application number: 11/942,672 - Filed: 2007-11-19 - Published: 2008-07-31 - Granted: 2013-09-24 - Earliest claimed: 2004-06-10 - Assignees: Agency for Science, Technology and Research - Applicants: Yi Yan Yang; Kumaresh Soppimath - Inventors: Yi Yan Yang; Kumaresh Soppimath - Web page: https://patentgrep.com/patent/US8541013B2 ## CPC - A61K 9/167: {with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface (with further drug-free outer coating A61K9/5073)} - A61P 25/00: Drugs for disorders of the nervous system - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 35/00: Antineoplastic agents - C08F 220/54: Amides {, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide} - C08F 220/62: Monocarboxylic acids having ten or more carbon atoms; Derivatives thereof (copolymers of drying oils C08F242/00) - C08F 293/005: {using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent} - C08L 33/08: Homopolymers or copolymers of acrylic acid esters - C08L 33/26: Homopolymers or copolymers of acrylamide or methacrylamide - C08L 53/00: Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers - 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 - C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06) ## Abstract The invention is directed to a copolymer comprising at least three types of monomeric units, said three types of monomeric units comprising: a temperature-sensitive unit, a hydrophilic unit, and a hydrophobic unit comprising at least one pH-sensitive moiety; wherein said hydrophobic monomeric unit is derived from a copolymerizable unsaturated fatty acid. ## Claims ### Claim 1 An amphiphilic block copolymer comprising at least three types of monomeric units, said three types of monomeric units comprising: a temperature-sensitive monomeric unit, wherein the temperature-sensitive monomeric unit imparts temperature-induced phase separation character to the amphiphilic block copolymer, a hydrophilic monomeric unit, wherein the hydrophilic monomeric unit has one or more polar functionalities, and a hydrophobic monomeric unit comprising at least one pH-sensitive moiety; wherein said hydrophobic monomeric unit is derived from a copolymerisable unsaturated fatty acid; wherein said unsaturated fatty acid imparts hydrophobic character to the amphiphilic block copolymer; wherein the fatty acid comprises 5 to 50 or more main chain carbon atoms; wherein the fatty acid comprises one carbon-carbon double bond (monounsaturated); and wherein the amphiphilic block copolymer exhibits a lower critical solution temperature (LCST) dependent on environmental pH. ### Claim 2 (depends on 1) The amphiphilic block copolymer of claim 1, wherein the fatty acid is selected from the group consisting of (E)-9-Octadecenoic acid, (Z)-9-Octadecenoic acid, (Z)-11-Octadecenoic acid, (E)-9-Hexadecenoic acid, (Z)-9-Hexadecenoic acid, (Z)-9-Tetradecenoic acid, (Z)-11-Eicosenoic acid, (Z)-13-Docosenoic Acid and (Z)-15-Tetracosaenoic Acid. ### Claim 3 (depends on 1) The amphiphilic block copolymer of claim 1, wherein the fatty acid is an omega-1 fatty acid. ### Claim 4 (depends on 3) The amphiphilic block copolymer of claim 3, wherein the fatty acid is selected from the group consisting of 4-pentenoic acid, 7-octenoic acid, 10-undecenoic acid, 15-hexadecenoic acid, and 19-eicosenoic acid. ### Claim 5 (depends on 1) The amphiphilic block copolymer of claim 1, wherein the temperature sensitive monomeric unit is derived from the group consisting of N-acroylpiperadine, N-t-butylacrylamide, N-piperidyl-methacrylamide and N-isopropylacrylamide. ### Claim 6 (depends on 1) The amphiphilic block copolymer of claim 1, wherein the hydrophilic monomeric unit is derived from the group consisting of acrylic acid, acrylamide, acrylate, and substituted derivatives thereof. ### Claim 7 (depends on 6) The amphiphilic block copolymer of claim 6, wherein the acrylamide is selected from the group consisting of acrylamide (AAm), N,N′-dimethylacrylamide (DMAAm), and N-(hydroxymethyl)acrylamide. ### Claim 8 (depends on 1) The amphiphilic block copolymer of claim 1, further comprising a terminal group comprising at least one moiety selected from the group consisting of a terminating moiety, a ligand, a drug, a tag, a radioimmunoconjugate, a chemical moiety and a spacer. ### Claim 9 (depends on 8) The amphiphilic block copolymer of claim 8, wherein the terminating moiety comprises a functional group selected from the group consisting of a hydroxyl group, a carboxyl group and an amino group. ### Claim 10 (depends on 9) The amphiphilic block copolymer of claim 9, wherein the terminating moiety is introduced by chain transfer agents or group transfer agents. ### Claim 11 (depends on 9) The amphiphilic block copolymer of claim 9, wherein the terminating moiety is introduced by living polymerisation methods. ### Claim 12 (depends on 9) The amphiphilic block copolymer of claim 9, wherein the terminating moiety is part of the monomeric unit of the polymer. ### Claim 13 (depends on 10) The amphiphilic block copolymer of claim 10, wherein the chain transfer agent is selected from the group consisting of chloroform, carbon tetrachloride, alkyl-mercaptans, aminoethanethiol, mercapto-propionic acid, mercapto-succinic acid, thioglycolic acid, mercaptoethanol and secondary alcohols of mercaptoethanol, alkyl halides, and salts of phosphorus acids with an oxidation number less than 5. ### Claim 14 (depends on 13) The amphiphilic block copolymer of claim 13, wherein the alkyl-mercaptans are selected from the group consisting of octanethiol, decanethiol, n-dodecanethiol or t-dodecanethiol. ### Claim 15 (depends on 8) The amphiphilic block copolymer of claim 8, wherein said ligand is attached to the functional group of the terminating moiety directly. ### Claim 16 (depends on 8) The amphiphilic block copolymer of claim 8, wherein said ligand is attached to the terminating moiety by a spacer. ### Claim 17 (depends on 16) The amphiphilic block copolymer of claim 16, wherein said spacer comprises more than 10 main chain atoms. ### Claim 18 (depends on 17) The amphiphilic block copolymer of claim 17, wherein said ligand is selected from the group consisting of small targeting molecules, proteins, peptides and carbon hydrates. ### Claim 19 (depends on 17) The amphiphilic block copolymer of claim 17, wherein the spacer comprises poly(ethylene glycol) and poly(propylene glycol). ### Claim 20 (depends on 1) The amphiphilic block copolymer of claim 1, wherein the copolymer is a random copolymer.