# US 2002/0058733 A1 · Methods of using primer molecules for enhancing the mechanical performance of tissue adhesives and sealants > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2002/0058733 A1 - Document ID: US20020058733A1 - Status: Published application - Kind: A1 - Application number: 09/888,225 - Filed: 2001-06-22 - Published: 2002-05-16 - Earliest claimed: 1997-06-20 - Assignees: Protein Polymer Technologies, Inc. - Inventors: Erwin R. Stedronsky - Web page: https://patentgrep.com/patent/US20020058733A1 ## CPC - A61L 24/001: {Use of materials characterised by their function or physical properties} - A61L 24/106: {Fibrin; Fibrinogen} - Y10T 428/2865: including monomer or polymer of carbohydrate [e.g., starch, dextrin, etc.] Or protein [e.g., casein, animal protein, etc.] Or derivative thereof - Y10T 428/31536: Including interfacial reaction product of adjacent layers - Y10T 428/31754: Natural source-type polyamide - 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) - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract The present invention concerns novel methods for enhancing the mechanical performance of tissue adhesives and sealants which comprises employing a primer molecule in association with a tissue adhesive or sealant, wherein the primer molecule serves to enhance the strength of the interface between the tissue and the adhesive matrix. The primer molecules described herein function to interact with a protein present in the tissue, thereby altering its characteristics to make it more amenable to bonding with the adhesive matrix. Primer molecules may be applied to the tissue independently from the tissue adhesive or sealant or may be mixed with the tissue adhesive or sealant prior to application to the tissue. ## Claims ### Claim 1 A method of adhering a tissue adhesive to a tissue, said method comprising: applying to said tissue (a) a primer molecule and (b) a tissue adhesive, said primer molecule being capable of physically interacting with a component present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue adhesive. ### Claim 2 (depends on 1) The method according to claim 1, wherein said component present in said tissue is a protein. ### Claim 3 A method of maintaining separated tissues in proximate relationship, said method comprising: applying to said separated tissues (a) a primer molecule and (b) a tissue adhesive, said primer molecule being capable of physically interacting with a component present in said separated tissues and thereby rendering said separated tissue capable of forming a bonded interface with said tissue adhesive, wherein (a) and (b) are applied in an amount effective to maintain said separated tissues in proximate relationship when said separated tissues are brought into proximate relationship, ### Claim 4 (depends on 3) The method according to claim 3 which maintains said separated tissues in proximate relationship with greater bond strength than when said tissue adhesive is employed in the absence of said primer molecule. ### Claim 5 (depends on 3) The method according to claim 3, wherein said primer molecule is applied to said separated tissues before said tissue adhesive is applied to said separated tissues. ### Claim 6 (depends on 3) The method according to claim 3, wherein said tissue adhesive and said primer molecule are combined prior to application to said separated tissues. ### Claim 7 (depends on 3) The method according to claim 3, wherein said applying occurs prior to bringing said separated tissues into proximate relationship. ### Claim 8 (depends on 3) The method according to claim 3, wherein said primer molecule is a chaotropic agent. ### Claim 9 (depends on 8) The method according to claim 8, wherein said chaotropic agent is urea. ### Claim 10 (depends on 3) The method according to claim 3, wherein said primer molecule is a sulfonated aromatic compound or xanthene. ### Claim 11 (depends on 10) The method according to claim 10, wherein said sulfonated aromatic compound or xanthene is selected from the group consisting of Brilliant Blue G (Aldrich 20,140-5), Evan's Blue (Aldrich 20,633-4), Chicago Sky Blue 6B (Aldrich 20,138-3), Cibacron Blue 3GA (Sigma C9534), Cibacron Brilliant Yellow 3G-P (Aldrich 22,847-8), Brilliant Blue R (Aldrich 20,140-5), Lissamine Green B (Aldrich 19,958-3), Acid Blue 92 (Aldrich 21,042-0), Cibacron Brilliant Red 3B-A (Aldrich 22,845-1), Acid Red 97 (Aldrich 21,039-0), Trypan Blue (Aldrich 30,264-3), New Coccine (Aldrich 19,973-7), Orange G (Aldrich 86,128-6), Eosin Y (Aldrich 11,983-0), Eosin B (Aldrich 86,100-6), Erythrosin B (Aldrich 19,826-9) and Rose Bengal (Aldrich 19,825-0). ### Claim 12 (depends on 10) The method according to claim 10, wherein said sulfonated aromatic compound is Brilliant Blue G (Aldrich 20,140-5). ### Claim 13 (depends on 3) The method according to claim 3, wherein said primer molecule is a protein selected from the group consisting of fibrinogen, SELP8K and SELP0K-CS1. ### Claim 14 (depends on 3) The method according to claim 3, wherein said primer molecule is an oligopeptide. ### Claim 15 (depends on 3) The method according to claim 3, wherein said tissue adhesive comprises a polypeptide that is capable of being crosslinked. ### Claim 16 (depends on 3) The method according to claim 3, wherein said separated tissues comprise skin, bone, tendon, muscle or cartilage. ### Claim 17 (depends on 3) The method according to claim 3, wherein said component present in said separated tissue with which said primer molecule physically interacts is a protein selected from the group consisting of collagen, actin and myosin. ### Claim 18 A method of sealing a defect in tissue, said method comprising: applying to said defect (a) a primer molecule and (b) a tissue sealant, said primer molecule being capable of physically interacting with a protein present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue sealant, wherein (a) and (b) are applied to said defect in an amount effective to seal said defect. ### Claim 19 (depends on 18) The method according to claim 18, wherein said primer molecule is applied to said defect before said tissue sealant is applied to said defect. ### Claim 20 (depends on 18) The method according to claim 18, wherein said tissue sealant and said primer molecule are combined prior to application to said defect. ### Claim 21 (depends on 18) The method according to claim 18, wherein said primer molecule is selected from the group consisting of a chaotropic agent, a sulfonated aromatic compound, a xanthene, a protein and an oligopeptide. ### Claim 22 (depends on 18) The method according to claim 18, wherein said defect is a result of a surgical procedure. ### Claim 23 A composition of matter useful for forming a bonded interface with a tissue when said composition of matter is applied to said tissue, said composition of matter comprising: (a) a tissue adhesive or sealant; and (b) a primer molecule which is capable of physically interacting with a component present in said tissue and thereby rendering said tissue capable of forming a bonded interface with said tissue adhesive or sealant. ### Claim 24 (depends on 23) The composition of matter according to claim 23, wherein said primer molecule is selected from the group consisting of a chaotropic agent, a sulfonated aromatic compound, a xanthene, a protein and an oligopeptide. ### Claim 25 (depends on 23) A kit comprising the composition of matter according to claim 23.