# US 10,441,550 B2 · Nanofibrous materials as drug, protein, or genetic release vehicles > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,550 B2 - Document ID: US10441550B2 - Status: Granted - Kind: B2 - Application number: 15/046,675 - Filed: 2016-02-18 - Published: 2016-06-09 - Granted: 2019-10-15 - Earliest claimed: 2005-03-04 - Assignees: BioSurfaces, Inc.; Rhode Island Board of Education; Clemson University - Applicants: BioSurfaces, Inc.; Clemson University; Rhode Island Board of Education - Inventors: Matthew D. Phaneuf; Philip J. Brown; Martin J. Bide - Web page: https://patentgrep.com/patent/US10441550B2 ## CPC - A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)} - A61K 9/0092: {Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes} - A61K 31/337: having four-membered rings, e.g. taxol - A61K 31/4196: 1,2,4-Triazoles - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - B29C 48/05: Filamentary, e.g. strands - D01D 1/02: Preparation of spinning solutions - D01D 5/0038: {the fibre formed by solvent evaporation, i.e. dry electro-spinning} - D01F 6/62: from polyesters - D04H 1/435: Polyesters - D04H 1/728: by electro-spinning {(electro-spinning methods and apparatus D01D5/0007)} - D04H 3/011: Polyesters - D04H 3/02: characterised by the method of forming fleeces or layers, e.g. reorientation of yarns or filaments - D04H 3/16: with bonds between thermoplastic filaments produced in association with filament formation, e.g. immediately following extrusion - A61F 2/82: Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents (stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07) - A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)} - B29C 48/022: {characterised by the choice of material} - 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) - B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00) - D01D: MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS - D01F: CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS - D04H: MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL (weaving D03; knitting D04B; braiding D04C; net-making D04G; sewing D05B; tufting D05C; finishing non-woven fabrics D06); FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING {; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION}(non-woven fabrics having an intermediate or external layer of a different kind, e.g. of woven fabric, B32B) - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) ## Abstract The present invention is a bioactive, nanofibrous material construct which is manufactured using a unique electrospinning perfusion methodology. One embodiment provides a nanofibrous biocomposite material formed as a discrete textile fabric from a prepared liquid admixture of (i) a non-biodegradable durable synthetic polymer; (ii) a biologically active agent; and (iii) a liquid organic carrier. These biologically-active agents are chemical compounds which retain their recognized biological activity both before and after becoming non-permanently bound to the formed textile material; and will become subsequently released in-situ as discrete freely mobile agents front the fabric upon uptake of water from the ambient environment. ## Claims ### Claim 1 A method of forming a fabricated textile comprising nanofibers by electrospinning perfusion, the method comprising the steps of: dissolving 19-20% weight per volume of a non-biodegradable polymer in hexafluoroisopropanol to provide an admixture, the dissolving occurring at an ice-cold temperature, wherein the non-biodegradable polymer is not polytetrafluoroethylene, polypropylene, or polyethylene; loading the admixture into an electrospinning perfusion instrument which can be set at a specified flow rate; applying an electric current of 15-20 kV to a needle of the electrospinning perfusion instrument; perfusing the admixture onto a target surface at the specified flow rate, the step of perfusing occurring at a temperature between about 20° C. and about 50° C. to provide a perfused nanofiber having a diameter from 100 nm to 3000 nm; and permitting trace hexafluoroisopropanol to be removed from the perfused nanofiber to form a fabricated textile. ### Claim 2 (depends on 1) The method of claim 1, further comprising dissolving at least one biologically-active agent such that the admixture comprises a mixture of the non-biodegradable polymer and the at least one biologically active agent. ### Claim 3 (depends on 1) The method of claim 1, wherein the step of permitting trace hexafluoroisopropanol to be removed is performed using a post-treatment process performed after the step of perfusing the admixture. ### Claim 4 (depends on 1) The method of claim 1, wherein the target surface is a mandrel. ### Claim 5 (depends on 1) The method of claim 1, wherein the target surface is a metallic stent that is slid onto a mandrel and coated with perfused material, and wherein the coated metallic stent is air-dried in a vacuum oven at 37° C. for 48 hours to remove residual hexafluoroisopropanol. ### Claim 6 (depends on 1) The method of claim 1, wherein the non-biodegradable polymer is selected from the group consisting of a non-biodegradable polyester, a polyurethane, and combinations thereof. ### Claim 7 (depends on 1) The method of claim 1, wherein the target surface comprises a first portion and a second portion and the step of perfusing the admixture onto the target surface perfuses the admixture for a first period of time onto the first portion and for a second period of time onto the second portion, wherein the first period and the second period are different. ### Claim 8 (depends on 1) The method of claim 1, the method further comprising removing the perfused fabricated textile from the target surface. ### Claim 9 (depends on 4) The method of claim 4, wherein the perfused fabricated textile is formed into a tubular construct. ### Claim 10 (depends on 9) The method of claim 9, wherein the tubular construct has an internal diameter of at least 1 mm and less than 40 mm. ### Claim 11 (depends on 9) The method of claim 9, wherein the tubular construct has a length of at least about 1 cm and less than about 80 cm. ### Claim 12 (depends on 4) The method of claim 4, wherein the perfused fabricated textile coated mandrel is processed to remove traces of residual solvent and one edge of the perfused material is rolled towards an opposite end of the mandrel to achieve a desired thickness, and wherein the perfused material is cut along an opposite edge and the opposite edge is fused to form a rounded cuff shape. ### Claim 13 (depends on 8) The method of claim 8, wherein the perfused fabricated textile is a flat sheet with a width of at least 1 cm and a length of at least 1 cm. ### Claim 14 (depends on 13) The method of claim 13, further comprising fusing the perfused fabricated textile to a second flat sheet comprising a biodegradable polymer. ### Claim 15 (depends on 1) The method of claim 1, wherein the step of dissolving further comprises dissolving a biodegradable polymer such that the admixture comprises a mixture of the non-biodegradable polymer and the biodegradable polymer. ### Claim 16 (depends on 2) The method of claim 2, wherein the at least one biologically-active agent is maintained at a temperature below about 50° C. during the steps of dissolving, loading, perfusing and permitting such that the at least one biologically active agent maintains the same biological activity after the method as the at least one biologically active agent had before the method. ### Claim 17 (depends on 1) The method of claim 1, wherein the target surface is configured to create alignment of polymer nanofibers in a toroidal direction with respect to a revolution of the target surface. ### Claim 18 (depends on 17) The method of claim 17, wherein the polymer nanofibers are removed from the target surface and manually twisted and elongated to their yield strain to produce a single-strand yarn shape. ### Claim 19 (depends on 18) The method of claim 18, wherein the single-strand yarn shape has a diameter between about 0.025 mm and about 2 mm. ### Claim 20 (depends on 1) The method of claim 1, wherein a 15-30 centimeter jet gap exists between the needle and the target surface. ### Claim 21 (depends on 1) The method of claim 1, wherein a 15 centimeter jet gap exists between the needle and the target surface. ### Claim 22 (depends on 1) The method of claim 1, wherein the fabricated textile is formed into a medical device without the use of an underlying scaffold.