# US 9,433,700 B2 · Tissue sealant compositions, vascular closure devices, and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,433,700 B2 - Document ID: US9433700B2 - Status: Granted - Kind: B2 - Application number: 13/266,161 - Filed: 2010-04-27 - Published: 2012-02-16 - Granted: 2016-09-06 - Earliest claimed: 2009-04-27 - Assignees: MediBeacon Inc. - Applicants: Bob O. Basore; William L. Neumann; Richard B. Dorshow; Raghavan Rajagopalan - Inventors: Bob O. Basore; William L. Neumann; Richard B. Dorshow; Raghavan Rajagopalan - Web page: https://patentgrep.com/patent/US9433700B2 ## CPC - A61L 24/102: {Collagen} - A61L 24/001: {Use of materials characterised by their function or physical properties} - A61L 24/0015: {Medicaments; Biocides} - A61L 24/0042: {Materials resorbable by the body} - A61L 24/046: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds (A61L24/043 takes precedence)} - A61L 24/106: {Fibrin; Fibrinogen} - A61L 24/108: {Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106} - A61L 2300/418: Agents promoting blood coagulation, blood-clotting agents, embolising agents - A61L 2300/442: Colorants, dyes - A61L 2300/604: Biodegradation - A61L 2400/04: Materials for stopping bleeding - A61L 2430/20: for reconstruction of the heart, e.g. heart valves - A61L 2430/34: for soft tissue reconstruction - 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) ## Abstract The present invention provides tissue sealant compositions and vasculature closure devices useful for the optical detection of tissue seal and/or clot formation. Compositions and devices of the present invention comprise optical dyes which undergo an observable change as the compositions and/or devices are incorporated into a tissue seal and/or clot, for example a change in fluorescence quantum yield and/or a change in visual color including a change in emission and/or absorption wavelength. Tissue sealants and vasculature closure devices of the present invention are useful for visualizing seal and/or clot formation, for example, during or after surgical procedures, after catheter removal, etc. The present invention further provides methods for formation and optical detection of tissue seals or vasculature puncture closures as well as medical kits useful for the formation and optical detection of tissue seals or vasculature puncture closures. ## Claims ### Claim 1 A tissue sealant comprising: an adhesive material that is activated to form a seal when contacted with a biological tissue; and an optical dye noncovalently associated with the adhesive material; wherein the optical dye exhibits a first optical condition prior to activation of the adhesive material and exhibits a second optical condition that is distinguishable from the first optical condition after activation of the adhesive material, wherein the first optical condition of the optical dye is a first fluorescence quantum yield prior to activation of the adhesive material and the second optical condition of the optical dye is a second fluorescence quantum yield after activation of the adhesive material, wherein the second fluorescence quantum yield is different from the first fluorescence quantum yield; wherein the first fluorescence quantum yield is substantially equal to 0 and the second fluorescence quantum yield is greater than or equal to 0.01, or wherein the second fluorescence quantum yield is greater than the first fluorescence quantum yield by at least a factor of 1.5 or is less than the first fluorescence quantum yield by at least a factor of 1.5, wherein activation of the adhesive material incorporates the optical dye into the tissue seal, fibrin network, or clot; immobilizes the optical dye in the tissue seal, fibrin network, or clot, or rigidifies the optical dye, thereby providing a change from the first optical condition to the second optical condition; and wherein activation of the adhesive material initiates a coagulation cascade in a subject. ### Claim 2 (depends on 1) The tissue sealant of claim 1, wherein activation of the adhesive material comprises formation of a tissue seal, a fibrin network, a synthetic polymer network or a clot. ### Claim 3 (depends on 1) The tissue sealant of claim 1, wherein the optical condition is absorbance, fluorescence, color, reflectance or an optoacoustic condition. ### Claim 4 (depends on 1) The tissue sealant of claim 1, wherein the first optical condition of the optical dye is a first emission wavelength or distribution of emission wavelengths prior to activation of the adhesive material and the second optical condition of the optical dye is a second emission wavelength or distribution of emission wavelengths after activation of the adhesive material, wherein the second emission wavelength or distribution of emission wavelengths is different from the first emission wavelength or distribution of emission wavelengths; wherein the second emission wavelength is greater than or less than the first emission wavelength by at least 20 nanometers, or wherein at least a portion of the second distribution of emission wavelengths is greater than or less than at least a portion of the first distribution of emission wavelengths by at least 20 nanometers. ### Claim 5 (depends on 1) The tissue sealant of claim 1, wherein the first optical condition of the optical dye is a first absorption wavelength corresponding to an absorption maximum in the visible or near infrared regions of the electromagnetic spectrum prior to activation of the adhesive material and the second optical condition of the optical dye is a second absorption wavelength corresponding to an absorption maximum in the visible or near infrared regions of the electromagnetic spectrum after activation of the adhesive material, wherein the second absorption wavelength is different from the first absorption wavelength; wherein the second absorption wavelength is greater than the first absorption wavelength by at least 20 nanometers, or wherein the second absorption wavelength is less than the first absorption wavelength by at least 20 nanometers. ### Claim 6 (depends on 1) The tissue sealant of claim 1, wherein the adhesive material comprises collagen, fibrin, fibrinogen, fibronectin, prothrombin, thrombin, thromboplastin, factor V, factor X, factor XIII, a coagulation factor, a platelet factor, a coagulation activator, a platelet activator, a vasoconstrictor, a fibrinolysis inhibitor, a crosslinker, a glycosaminoglycan, a polysaccharide, a biopolymer, a synthetic polymer, or a growth factor. ### Claim 7 (depends on 1) The tissue sealant of claim 1, wherein the adhesive material comprises a polycyanoacrylate or monomers thereof, a polyethylene glycol or monomers thereof, a succinimide-derivatized polyethylene glycol or monomers thereof, a thiol-derivatized polyethylene glycol or monomers thereof, a polyisocyanate or monomers thereof, a polyacrylate or monomers thereof, a polyamine or monomers thereof, a polyamide or monomers thereof, or a polyurethane or monomers thereof. ### Claim 8 (depends on 1) The tissue sealant of claim 1, wherein the optical dye comprises a group corresponding to a pyrazine, a thiazole, a phenylxanthene, a phenothiazine, a phenoselenazine, a cyanine, an indocyanine, a squaraine, a dipyrrolo pyrimidone, an anthraquinone, a tetracene, a quinoline, an acridine, an acridone, a phenanthridine, an azo dye, a rhodamine, a phenoxazine, an azulene, an azaazulene, a triphenyl methane dye, an indole, a benzoindole, an indocarbocyanine, a Nile Red dye, a thionin dye, an isosulfan blue dye, or a benzoindocarbocyanine. ### Claim 9 (depends on 1) The tissue sealant of claim 1, wherein the first optical condition is presence of a color and the second optical condition is absence of a color. ### Claim 10 (depends on 1) The tissue sealant of claim 1, wherein the first optical condition is absence of color and the second optical condition is presence of a color. ### Claim 11 (depends on 1) The tissue sealant of claim 1, wherein the optical dye is isosulfan blue. ### Claim 12 (depends on 1) The tissue sealant of claim 1, wherein the optical dye is indocyanine green. ### Claim 13 (depends on 1) The tissue sealant of claim 1, wherein the optical condition is color. ### Claim 14 A tissue sealant comprising: an adhesive material that is activated to form a seal when contacted with a biological tissue; and an optical dye noncovalently associated with the adhesive material; wherein the optical dye exhibits a first optical condition prior to activation of the adhesive material and exhibits a second optical condition that is distinguishable from the first optical condition after activation of the adhesive material, wherein the first optical condition of the optical dye is a first fluorescence quantum yield prior to activation of the adhesive material and the second optical condition of the optical dye is a second fluorescence quantum yield after activation of the adhesive material, wherein the second fluorescence quantum yield is different from the first fluorescence quantum yield; wherein the first fluorescence quantum yield is substantially equal to 0 and the second fluorescence quantum yield is greater than or equal to 0.01, or wherein the second fluorescence quantum yield is greater than the first fluorescence quantum yield by at least a factor of 1.5 or is less than the first fluorescence quantum yield by at least a factor of 1.5, wherein activation of the adhesive material incorporates the optical dye into the tissue seal, fibrin network, or clot; immobilizes the optical dye in the tissue seal, fibrin network, or clot, or rigidifies the optical dye, thereby providing a change from the first optical condition to the second optical condition; and wherein the adhesive material comprises collagen, fibrin, fibrinogen, fibronectin, prothrombin, thrombin, thromboplastin, factor V, factor X, factor XIII, a coagulation factor, a platelet factor, a coagulation activator, a platelet activator, a vasoconstrictor, a fibrinolysis inhibitor, a crosslinker, a glycosaminoglycan, a polysaccharide, a biopolymer, a synthetic polymer, or a growth factor. ### Claim 15 (depends on 14) The tissue sealant of claim 14, wherein activation of the adhesive material initiates a coagulation cascade in a subject. ### Claim 16 (depends on 14) The tissue sealant of claim 14, wherein activation of the adhesive material comprises formation of a tissue seal, a fibrin network, a synthetic polymer network or a clot. ### Claim 17 (depends on 14) The tissue sealant of claim 14, wherein the optical condition is absorbance, fluorescence, color, reflectance or an optoacoustic condition. ### Claim 18 (depends on 14) The tissue sealant of claim 14, wherein the first optical condition of the optical dye is a first emission wavelength or distribution of emission wavelengths prior to activation of the adhesive material and the second optical condition of the optical dye is a second emission wavelength or distribution of emission wavelengths after activation of the adhesive material, wherein the second emission wavelength or distribution of emission wavelengths is different from the first emission wavelength or distribution of emission wavelengths; wherein the second emission wavelength is greater than or less than the first emission wavelength by at least 20 nanometers, or wherein at least a portion of the second distribution of emission wavelengths is greater than or less than at least a portion of the first distribution of emission wavelengths by at least 20 nanometers. ### Claim 19 (depends on 14) The tissue sealant of claim 14, wherein the first optical condition of the optical dye is a first absorption wavelength corresponding to an absorption maximum in the visible or near infrared regions of the electromagnetic spectrum prior to activation of the adhesive material and the second optical condition of the optical dye is a second absorption wavelength corresponding to an absorption maximum in the visible or near infrared regions of the electromagnetic spectrum after activation of the adhesive material, wherein the second absorption wavelength is different from the first absorption wavelength; wherein the second absorption wavelength is greater than the first absorption wavelength by at least 20 nanometers, or wherein the second absorption wavelength is less than the first absorption wavelength by at least 20 nanometers. ### Claim 20 (depends on 14) The tissue sealant of claim 14, wherein the optical dye comprises a group corresponding to a pyrazine, a thiazole, a phenylxanthene, a phenothiazine, a phenoselenazine, a cyanine, an indocyanine, a squaraine, a dipyrrolo pyrimidone, an anthraquinone, a tetracene, a quinoline, an acridine, an acridone, a phenanthridine, an azo dye, a rhodamine, a phenoxazine, an azulene, an azaazulene, a triphenyl methane dye, an indole, a benzoindole, an indocarbocyanine, a Nile Red dye, a thionin dye, an isosulfan blue dye, or a benzoindocarbocyanine. ### Claim 21 (depends on 14) The tissue sealant of claim 14, wherein the first optical condition is presence of a color and the second optical condition is absence of a color. ### Claim 22 (depends on 14) The tissue sealant of claim 14, wherein the first optical condition is absence of color and the second optical condition is presence of a color. ### Claim 23 (depends on 14) The tissue sealant of claim 14, wherein the optical dye is isosulfan blue. ### Claim 24 (depends on 14) The tissue sealant of claim 14, wherein the optical dye is indocyanine green. ### Claim 25 (depends on 14) The tissue sealant of claim 14, wherein the optical condition is color.