# US 2016/0250375 A1 · Reinforced adhesive complex coacervates and methods of making and using thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2016/0250375 A1 - Document ID: US20160250375A1 - Status: Published application - Kind: A1 - Application number: 15/131,583 - Filed: 2016-04-18 - Published: 2016-09-01 - Earliest claimed: 2010-05-24 - Assignees: University of Utah Research Foundation - Applicants: University of Utah Research Foundation - Inventors: Russell J. STEWART - Web page: https://patentgrep.com/patent/US20160250375A1 ## CPC - A61L 24/046: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds (A61L24/043 takes precedence)} - A61L 24/0015: {Medicaments; Biocides} - A61L 24/02: containing inorganic materials - A61L 24/043: {Mixtures of macromolecular materials} - A61L 24/06: obtained by reactions only involving carbon-to-carbon unsaturated bonds {(A61L24/043, A61L24/046 take precedence)} - A61L 24/10: Polypeptides; Proteins {(A61L24/043 takes precedence)} - A61L 27/26: Mixtures of macromolecular compounds - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - A61P 5/00: Drugs for disorders of the endocrine system - A61P 19/00: Drugs for skeletal disorders - A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease - A61P 27/02: Ophthalmic agents - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 37/02: Immunomodulators - C08F 8/00: Chemical modification by after-treatment (graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C) - C08F 8/06: Oxidation - A61L 2300/62: Encapsulated active agents, e.g. emulsified droplets - A61L 2430/16: for reconstruction of eye parts, e.g. intraocular lens, cornea - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS ## Abstract Described herein is the synthesis of reinforced adhesive complex coacervates and their use thereof. The reinforced adhesive complex coacervates are composed of (a) at least one polycation, (b) at least one polyanion, and (c) a reinforcing component. The adhesive complex coacervates described herein can be subsequently cured to produce strong, cohesive adhesives. The reinforced adhesive complex coacervates have several desirable features when compared to conventional adhesives. The reinforced adhesive complex coacervates are effective in wet or underwater applications. The reinforced adhesive complex coacervates described herein, being phase separated from water, can be applied underwater without dissolving or dispersing into the water. The reinforced adhesive complex coacervates have numerous biological applications as bioadhesives and bioactive delivery devices. In particular, the reinforced adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, wet tissues in physiological conditions. ## Claims ### Claim 1 An adhesive comprising a complex coacervate, wherein the complex coacervate comprises (a) at least one polycation, (b) at least one polyanion, and (c) a reinforcing agent. ### Claim 2 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polycation comprises a polyamino compound. ### Claim 3 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polycation comprises a polysaccharide, a natural protein, a recombinant protein, or a synthetic polyamine. ### Claim 4 (depends on 3) The adhesive complex coacervate of claim 3, wherein the amino group comprises (1) an alkylamino group, or (2) a heteroaryl group, a guanidinyl group, or an aromatic group substituted with one or more amino groups. ### Claim 5 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polycation comprises a natural protein. ### Claim 6 (depends on 5) The adhesive complex coacervate of claim 5, wherein the natural protein comprises one or more guanidinyl groups. ### Claim 7 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polycation comprises a polymer comprising at least one fragment comprising the formula I wherein R1, R2, and R3 are, independently, hydrogen or an alkyl group, X is oxygen or NR5, where R5 is hydrogen or an alkyl group, and m is from 1 to 10, or the pharmaceutically-acceptable salt thereof. ### Claim 8 (depends on 7) The adhesive complex coacervate of claim 7, wherein R1, R2, and R3 are methyl, X is O, and m is 3. ### Claim 9 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polyanion comprises two or more sulfate, sulfonate, carboxylate, borate, boronate, phosphonate, or phosphate groups. ### Claim 10 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polyanion comprises a polyphosphate. ### Claim 11 (depends on 10) The adhesive complex coacervate of claim 10, wherein the polyphosphate comprises a natural polymer or a synthetic polymer. ### Claim 12 (depends on 10) The adhesive complex coacervate of claim 10, wherein the polyphosphate comprises a polyacrylate comprising one or more pendant phosphate groups. ### Claim 13 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polyanion comprises a polymer comprising at least one fragment comprising the formula X wherein R4 is hydrogen or an alkyl group; n is from 1 to 10; Y is oxygen, sulfur, or NR30, wherein R30 is hydrogen, an alkyl group, or an aryl group; Z is an anionic group or a group that can be converted to an anionic group, or the pharmaceutically-acceptable salt thereof. ### Claim 14 (depends on 13) The adhesive complex coacervate of claim 13, wherein Z is sulfate, sulfonate, carboxylate, borate, boronate, a substituted or unsubstituted phosphate, or a phosphonate. ### Claim 15 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polyanion comprises a polymer comprising at least one fragment comprising the formula II wherein R4 is hydrogen or an alkyl group, and n is from 1 to 10, or the pharmaceutically-acceptable salt thereof. ### Claim 16 (depends on 15) The adhesive complex coacervate of claim 15, wherein R4 is methyl and n is 2. ### Claim 17 (depends on 1) The adhesive complex coacervate of claim 1, wherein the reinforcing component comprises a particle, wherein the particle comprises a metal oxide, a ceramic particle, a silica particle, or a water insoluble inorganic salt. ### Claim 18 (depends on 1) The adhesive complex coacervate of claim 1, wherein the reinforcing component comprises a fiber. ### Claim 19 (depends on 1) The adhesive complex coacervate of claim 1, wherein the reinforcing component comprises a metal oxide particle. ### Claim 20 (depends on 1) The adhesive complex coacervate of claim 1, wherein the reinforcing component comprises a metal particle. ### Claim 21 (depends on 20) The adhesive complex coacervate of claim 20, wherein the metal particle is platinum, gold, or tantalum. ### Claim 22 (depends on 1) The adhesive complex coacervate of claim 1, wherein the polycation comprises a natural protein comprising one or more guanidinyl groups, the polyanion comprises a polyphosphate, and the reinforcing component comprises a metal oxide particle. ### Claim 23 (depends on 1) The adhesive complex coacervate of claim 1, wherein the coacervate further comprises one or more bioactive agents encapsulated in the coacervate. ### Claim 24 (depends on 1) A method for inhibiting blood flow in a blood vessel of a subject comprising introducing the adhesive complex coacervate of claim 1 into the vessel.