# US 10,441,675 B2 · Joining and/or sealing tissues through photo-activated cross-linking of matrix proteins > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,675 B2 - Document ID: US10441675B2 - Status: Granted - Kind: B2 - Application number: 15/494,622 - Filed: 2017-04-24 - Published: 2017-08-17 - Granted: 2019-10-15 - Earliest claimed: 2006-02-14 - Assignees: Cook Medical Technologies LLC - Applicants: Cook Medical Technologies LLC - Inventors: Alan George Brownlee; Christopher Malcolm Elvin - Web page: https://patentgrep.com/patent/US10441675B2 ## CPC - A61L 24/106: {Fibrin; Fibrinogen} - A61L 24/0015: {Medicaments; Biocides} - A61L 24/02: containing inorganic materials - A61L 24/10: Polypeptides; Proteins {(A61L24/043 takes precedence)} - C08J 3/24: Crosslinking, e.g. vulcanising, of macromolecules (mechanical aspects B29C35/00; crosslinking agents C08K) - C09J 189/00: Adhesives based on proteins; Adhesives based on derivatives thereof - A61L 2400/04: Materials for stopping bleeding - C08J 2389/00: Characterised by the use of proteins; Derivatives thereof - 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) - C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29) - C09J: ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES (preparation of glue or gelatine C09H) ## Abstract A method of joining and/or sealing tissues in a surgical procedure or medical treatment, comprising the steps of: (1) applying a matrix protein, a photoactivatable metal-ligand complex and an electron acceptor to a tissue portion; (2) irradiating said tissue portion to photoactivate the photoactivatable metal-ligand complex; thereby initiating a cross-linking reaction of the matrix protein to seal said tissue portion or join said tissue portion to an adjacent tissue portion. ## Claims ### Claim 1 A closure for a bleeding wound comprising: a substrate suitable for application to a wound to stem bleeding; and a liquid tissue adhesive carried by said substrate, said liquid tissue adhesive comprising a matrix protein, a photoactivatable metal-ligand complex, and an electron acceptor, wherein said matrix protein, said photoactivatable metal-ligand complex, and said electron acceptor are present in an amount effective to cause cross-linking reactions between said matrix protein to form a cross-linked protein matrix upon irradiation of said liquid tissue adhesive after implantation. ### Claim 2 (depends on 1) The closure of claim 1 wherein the matrix protein is selected from the group consisting of: fibrinogen, fibrin, collagen, fibronectin, keratin, and laminin, or admixtures thereof. ### Claim 3 (depends on 1) The closure of claim 1 wherein the photoactivatable metal-ligand is an Ru(II)/Pd(II), Cu(II), Ni(II), Mn(II), or Fe(III) complex. ### Claim 4 (depends on 3) The closure of claim 3 wherein the complex is an Ru(II) bipyridyl complex, a Pd(II) porphyrin complex, a sulfonatophenyl Mn(II) complex, or a Fe(III) protoporphyrin complex. ### Claim 5 (depends on 4) The closure of claim 4 wherein the complex is a tris (bipyridyl) Ru(II) complex. ### Claim 6 (depends on 5) The closure of claim 5 wherein the complex is tris (bipyridyl) Ru(II) dichloride. ### Claim 7 (depends on 1) The closure of claim 1 wherein the electron acceptor is a persulfate, periodate, perbromate, or a perchlorate compound. ### Claim 8 (depends on 7) The closure of claim 7 wherein the electron acceptor is a persulfate compound. ### Claim 9 (depends on 8) The closure of claim 8 wherein the electron acceptor is ammonium persulfate or sodium persulfate. ### Claim 10 (depends on 1) The closure of claim 1 further comprising a drug or other therapeutic agent. ### Claim 11 (depends on 1) The closure of claim 1 wherein the substrate is a collagen sheet, bandage, gauze, cloth, tampon, membrane, or sponge. ### Claim 12 (depends on 1) The closure of claim 1, wherein said tissue adhesive is coated on an outer surface of said 33. ### Claim 13 (depends on 1) The closure of claim 1, wherein said substrate suitable for application to a wound to stem bleeding is impregnated with said tissue adhesive. ### Claim 14 A light activated tissue adhesive wound dressing comprising: a light activated liquid absorbable medical adhesive, the liquid absorbable medical adhesive adherable to patient tissue so as to provide a hemostatic seal, the absorbable medical adhesive comprising: a matrix protein; a photoactivatable metal-ligand complex selected to absorb light in the visible region, said photoactivatable metal-ligand comprising a Ru(II), Pd(II), Cu(II), Ni(II), Mn(II), or Fe(III) complex; and an electron acceptor, and wherein said matrix protein, said photoactivatable metal-ligand complex, and said electron acceptor are present in an amount effective to form a cross-linked protein matrix comprising said matrix protein upon irradiation of said liquid absorbable medical adhesive. ### Claim 15 (depends on 14) The light activated tissue adhesive wound dressing of claim 14 wherein the complex is an Ru(II) bipyridyl complex, a Pd(II) porphyrin complex, a sulfonatophenyl Mn(II) complex, or a Fe(III) protoporphyrin complex. ### Claim 16 (depends on 15) The light activated tissue adhesive wound dressing of claim 15 wherein the complex is a tris (bipyridyl) Ru(II) complex. ### Claim 17 (depends on 16) The light activated tissue adhesive wound dressing of claim 16 wherein the complex is tris (bipyridyl) Ru(II) dichloride. ### Claim 18 (depends on 14) The light activated tissue adhesive wound dressing of claim 14 wherein the electron acceptor is a persulfate, periodate, perbromate, or a perchlorate compound. ### Claim 19 (depends on 18) The light activated tissue adhesive wound dressing of claim 18 wherein the electron acceptor is ammonium persulfate, or sodium persulfate. ### Claim 20 (depends on 14) The light activated tissue adhesive wound dressing of claim 14 further comprising an inert carrier. ### Claim 21 (depends on 14) The light activated tissue adhesive wound dressing of claim 14 wherein said adhesive is a lyophilized admixture. ### Claim 22 A closure for a bleeding wound comprising: a substrate suitable for application to a bleeding wound; and a liquid tissue adhesive carried by said substrate, said liquid tissue adhesive comprising a matrix protein, a photoactivatable metal-ligand complex, and an electron acceptor, wherein said matrix protein, said photoactivatable metal-ligand complex, and said electron acceptor are present in an amount effective to cause cross-linking reactions between said matrix protein to form a cross-linked protein matrix upon irradiation of said liquid tissue adhesive after implantation, such that said closure is effective to provide a hemostatic seal over the bleeding wound.