WO2017170929A1 - Matériau composite pour implantation dans un organisme vivant - Google Patents

Matériau composite pour implantation dans un organisme vivant Download PDF

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Publication number
WO2017170929A1
WO2017170929A1 PCT/JP2017/013394 JP2017013394W WO2017170929A1 WO 2017170929 A1 WO2017170929 A1 WO 2017170929A1 JP 2017013394 W JP2017013394 W JP 2017013394W WO 2017170929 A1 WO2017170929 A1 WO 2017170929A1
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Prior art keywords
gel
composite material
poly
porous body
acid
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PCT/JP2017/013394
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English (en)
Japanese (ja)
Inventor
松彦 西澤
邦明 長峯
悌二 冨永
佳克 齋木
陽一 荒井
仁 新倉
栄二 井樋
幸夫 香取
真樹 岩▲崎▼
敦寛 中川
奉洋 川口
邦泰 新妻
彩子 徳江
俊毅 遠藤
嘉廣 萩原
宗則 綿貫
橋本　功
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国立大学法人東北大学
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Publication of WO2017170929A1 publication Critical patent/WO2017170929A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
    • C08J5/12—Bonding of a preformed macromolecular material to the same or other solid material such as metal, glass, leather, e.g. using adhesives

Definitions

  • the present invention relates to a biofixing composite material. According to the present invention, the composite material can be easily and stably fixed to the mounting site.
  • an electrode that is a part of the device serves as an interface between the device and a living body.
  • Patent Document 1 a composite electrode body using an electrode material and a hydrogel excellent in biocompatibility as a substrate has been reported (Patent Document 1 and Non-Patent Document 1).
  • the electropolymerization of the conductive polymer is performed with the hydrogel (porous body) placed on the electrode material, and the conductive polymer is elongated from the surface of the electrode material in the vicinity of the electrode material.
  • a conductive adhesive layer is formed.
  • the electrode material and the hydrogel are firmly bonded to each other when the polymer chain constituting the hydrogel and the conductive polymer are entangled with each other.
  • an object of the present invention is to provide a composite material that can be easily and stably fixed to a target mounting site.
  • the composite material is a group consisting of a winding part, a sandwiching part, a convex part, and a suction part. It has been found that a composite material can be easily and stably fixed in vivo by having a structure for biological fixation selected from The present invention is based on these findings.
  • a biofixing composite material characterized by comprising: [2] The biofixation composite material according to [1], wherein the biofixation structure is formed by swelling, [3]
  • the porous body is agarose gel, collagen gel, glucomannan gel, polyacrylamide gel, polyacrylamide-2-methylpropanesulfonic acid, fibrin gel, polyvinyl alcohol gel, polyhydroxyethyl methacrylate gel, silicone hydrogel, Polyvinyl pyrrolidone gel, polyethylene glycol gel, poly-2-acrylamido-2-methylpropane sulfonic acid gel, alginic acid gel, carrageenan gel, chitosan gel, poly N isopropyl acrylamide gel, acrylic acid gel, polystyrene s
  • the polymer is poly (3,4-ethylenedioxythiophene), polyacetylene, polypyrrole, polythiophene, polybithiophene, polyisothiophene, polydodecylthiophene, polyisonitethiophene, poly-3-hexylthiophene, polyaniline
  • One or more conductive polymers selected from the group consisting of polyisothianaphthene, polythiazyl, polyphenylene, polyfluorene, polydiacetylene, polyacene, polyparaphenylene, polythienylene vinylene, and polyphenylene sulfide, or poly ( (Meth) acrylic acid or a salt thereof (for example, poly (meth) acrylic acid or a salt thereof such as polyacrylic acid, polymethacrylic acid, or acrylic acid / alkyl methacrylate copolymer), polyethylene glycol (Meth) acrylate polymers (eg, PPEGDA or
  • the composite material can be easily stabilized at the attachment site. Can be fixed.
  • the biofixation structure selected from the group consisting of the sandwiching portion, the convex portion, and the suction cup portion is used to provide a living body that is rich in liquids such as body fluids. Can be easily and stably fixed to the target mounting site.
  • Photographs ((a) to (c)) showing that a wound portion is formed by swelling in the biofixing composite material having a wound portion of the present invention, a composite electrode for biological fixing on a sciatic nerve bundle collected from a rat A photograph (d) with a body wound, a continuous photograph (e) in the case where a composite electrode body for biological fixation is wound around a glass rod, a graph (f) showing the relationship between the number of surface modifications and the inner diameter of the wound portion, and tightening It is the graph (g) which showed the setup schematic of pressure measurement, and the measurement result. It is the photograph which showed that the clamping part was formed by swelling in the biofixation composite material which has a clamping part of this invention.
  • the composite material for biofixation of the present invention is a group in which a composite material in which a base material and a porous body are bonded is composed of a winding part, a sandwiching part, a convex part, and a sucker part. It has the structure for biological fixation selected from.
  • the biofixing composite material of the present invention is preferably a biofixing composite electrode body.
  • the porous body is preferably bonded by a polymer extending from the base material to the porous body.
  • the biofixing composite material of the present invention includes a biofixing structure selected from the group consisting of a winding part, a clamping part, a convex part, and a sucker part.
  • the biofixing composite material of the present invention is easily and stably fixed to the attachment site by the biofixing structure.
  • the biofixing composite material may have a biofixing structure from the beginning, or may be generated by a change in moisture content.
  • the biofixing composite material may have a biofixation structure as a part thereof, or the whole may be a biofixation structure.
  • the whole biofixation composite material can be a wrapping part or a sandwiching part.
  • the composite material for biological fixation of the present invention can be easily and stably fixed by the structure for biological fixation even in a body part where it is difficult to fix the composite material.
  • the body part where it is difficult to fix the composite material is, for example, a part where the blood is flowing in a turbulent flow at a high speed, such as the inner wall of the heart and the inner wall of the blood vessel, and the wall to be fixed is moving continuously.
  • Sites surrounded by walls made of smooth elastic fibers filled with secretions such as, difficult adhesion sites such as tendons, central nervous system (brain and spinal cord) made of soft tissue filled with cerebrospinal fluid, pelvis
  • difficult adhesion sites such as tendons
  • central nervous system brain and spinal cord
  • soft tissue filled with cerebrospinal fluid pelvis
  • Examples include a fine nervous system in a body surface such as a cavity, or a site where a peristaltic movement occurs during swallowing such as the digestive tract.
  • a winding part means the structure for fixing a composite material to a mounting part by winding around a mounting part.
  • the composite material for biological fixation of the present invention is entirely a wound portion.
  • the composite material for immobilization of a living body of the present invention generates a winding portion due to a change in moisture content.
  • a clamping part means the structure for fixing a composite material to a mounting part by pinching a mounting part.
  • the sandwiching portion fixes the composite material to the mounting site by sandwiching the mounting site between one end and the other end.
  • the composite material for biological fixation of the present invention as a whole is a sandwiching portion.
  • the composite material for immobilization of a living body according to the present invention generates a nipping portion due to a change in moisture content.
  • the biofixing composite material of the present invention includes one or more convex portions on the surface of the composite material in contact with the mounting site.
  • the convex portion prevents the composite material from being detached from the mounting site by friction.
  • Various shapes can be selected as the shape of the convex portion, and for example, a polygonal pyramid shape, a conical shape, a cylindrical shape, a prismatic shape, or a semicircular shape can be used.
  • the convex portions may be randomly arranged on the surface of the composite material in contact with the mounting site, or may be regularly arranged.
  • the number and size of the convex portions are not particularly limited as long as the effect of the present invention can be obtained, and can be appropriately set according to the mounting site.
  • the biofixing composite material of the present invention includes one or more suction cups on the surface of the composite material in contact with the mounting site.
  • the suction of the suction cup part prevents the composite material from coming off the mounting site.
  • the suction cups may be arranged randomly or regularly on the surface of the composite material in contact with the mounting site.
  • the composite material used in the present invention is a composite material including a base material and a porous body.
  • the substrate and the porous body are preferably bonded by a polymer extending from the substrate to the porous body.
  • the base material and the porous body can be firmly bonded by the binding with the polymer, but the present invention is not limited to this, and by including the base material and the porous body, Can be used.
  • a conductive substrate or an insulating substrate can be used as the substrate used in the present invention.
  • the conductive base material used for the composite material is not particularly limited as long as it has conductivity, and examples thereof include metals, carbon materials, conductive polymer materials, stretchable materials, semiconductors, and composite materials thereof. be able to.
  • the composite material of the present invention can be used as a composite electrode body.
  • the metal include gold, platinum, silver, titanium, aluminum, tungsten, copper, iron, and palladium.
  • the carbon material include carbon nanotube, ketjen black, glassy carbon, graphene, fullerene, carbon fiber, carbon fabric, and carbon aerogel.
  • Examples of the conductive polymer material include polyaniline, polyacetylene, polypyrrole, poly (3,4-ethylenedioxythiophene), poly (p-phenylene vinylene), polythiophene, or poly (p-phenylene sulfide).
  • Examples of the elastic material include urethane, silicone rubber, and fluorine rubber.
  • Examples of the semiconductor include silicon (Si), germanium, indium tin oxide (ITO), titanium oxide, copper oxide, and silver oxide. These may be used alone or in combination of two or more.
  • the insulating base material used for the composite material glass or a general resin or a resin composition containing the resin can be used.
  • the resin polyurethane, polypropylene, polylactic acid, poly (lactide-co-glycolide) copolymer, polydioxanone, acrylonitrile butadiene styrene copolymer, acrylic acid ester, acrylonitrile ethylene propylene rubber styrene copolymer, acrylonitrile styrene Copolymer, acrylonitrile styrene acrylate, polybutadiene, bismaleimide triazine, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, cyclic butyl terephthalate, cresol formaldehyde, carboxymethylcellulose, nitrocellulose, hydrin rubber, cellulose propionate, chlorine Vinyl chloride, chloroprene rubber, case
  • the glass is as a main component silicates, silicates herein contain SiO 2.
  • silicates herein contain SiO 2.
  • a conductive material is further used together with the composite material, and the conductive material and the porous body are brought into contact with each other. This allows the composite material to be used as an electrode or sensor.
  • a conductive material for example, the material used for the conductive base material can be used without any limitation.
  • the porous body contained in the composite material for biological fixation of the present invention is not limited as long as it has flexibility, but is preferably excellent in biocompatibility, such as a gel.
  • hydrogel is preferred.
  • the material forming the hydrogel includes agar, gelatin, agarose, xanthan gum, gellan gum, sclerotia gum, gum arabic, tragacanth gum, karaya gum, cellulose gum, tamarind gum, guar gum, locust bean gum, glucomannan, chitosan, Carrageenan, quince seed, galactan, mannan, starch, dextrin, curdlan, casein, pectin, collagen, fibrin, peptide, chondroitin sulfate such as sodium chondroitin sulfate, hyaluronic acid such as hyaluronic acid (mucopolysaccharide) and sodium hyaluronate Natural polymers such
  • the base material and the porous body are preferably bonded to each other by a polymer extending from the base material to the porous body.
  • the polymer that binds the base material and the porous body is not particularly limited, and examples thereof include a conductive polymer or an insulating polymer. When the conductive polymer or the insulating polymer extends from the base material into the porous body by polymerization, the base material and the porous body can be firmly bonded.
  • the conductive polymer is not particularly limited, but is poly (3,4-ethylenedioxythiophene) (hereinafter sometimes referred to as PEDOT), polyacetylene, polypyrrole, polythiophene, polybithiophene, polyisothione.
  • PEDOT poly (3,4-ethylenedioxythiophene)
  • polyacetylene polypyrrole
  • polythiophene polythiophene
  • polybithiophene polybithiophene
  • polyisothione polyisothione.
  • Thiophene polydodecylthiophene, polyisonite thiophene, poly-3-hexylthiophene, polyaniline, polyisothianaphthene, polythiazyl, polyphenylene, polyfluorene, polydiacetylene, polyacene, polyparaphenylene, polythienylene vinylene, polyphenylylene sulfide, Or a mixture of two or more thereof, preferably poly (3,4-ethylenedioxythiophene) or polypyrrole. These may be used alone or in combination of two or more.
  • the insulating polymer is not particularly limited, but poly (meth) acrylic acids such as polyacrylic acid, polymethacrylic acid, acrylic acid / alkyl methacrylate copolymer, and salts thereof; polyethylene glycol di (meth) acrylate Polymer (PPEGDA, PPEGDM), polyhydroxyethyl methacrylate, polyacrylamide, poly (N, N-dimethylacrylamide), poly-2-acrylamide-2-methylpropanesulfonic acid, poly (N-isopropylacrylamide), polyvinylpyrrolidone, Polystyrene sulfonic acid, polyethylene glycol, carboxyvinyl polymer, alkyl-modified carboxyvinyl polymer, maleic anhydride copolymer, polyalkylene oxide resin, poly (methyl vinyl ether) -Alt-maleic anhydride) and polyethylene glycol cross-linked product, polyethylene glycol cross-linked product, N-vinylacetamide cross-linked product, acrylamide cross
  • polyacrylamide poly (N, N-dimethylacrylamide), PPEGDA, and PPEGDM are preferred because there is no deformation according to the surrounding environment (the degree of swelling does not change with temperature, pH, etc.). These may be used alone or in combination of two or more.
  • the composite material may have a wiring for energization extending from the base material.
  • the composite material can also be produced by adhering a base material and a porous body.
  • a base material and a porous body are combined with a polymer extending from the base material to the porous body, it can be manufactured by the following manufacturing method (A) or (B).
  • the composite material of the present invention includes (1) a step of forming a substrate on a substrate for forming a substrate, (2 ) A step of forming a porous body so as to come into contact with the base material formed on the base material forming substrate; (3) Electrolytic polymerization is carried out in an electrolyte solution containing a conductive monomer; A step of bonding the base material and the porous body by polymerizing the conductive polymer, and (4) a step of peeling the base material forming substrate from the base material.
  • the method further includes a step of bringing an electrolyte solution containing a conductive monomer into contact with the surface of the material and forming a conductive polymer polymerization layer on the surface of the base material by electrolytic polymerization.
  • the substrate is preferably an electrode, and therefore the substrate forming substrate is preferably an electrode forming substrate.
  • Base material forming step (base material forming substrate)
  • the substrate for forming a substrate is not limited as long as the substrate pattern can be formed. Examples of the material include glass, plastic, cloth, and wood, but glass is preferable because it is flat and has low adhesion to the substrate.
  • the shape of the substrate for substrate formation is not limited, and a substrate pattern (electrode pattern) may be formed on a plate-shaped substrate, and the substrate pattern (electrode pattern) may be formed on the surface of a rod-shaped substrate. It may be formed.
  • Porous body formation process In a porous body formation process, a porous body is formed so that the base material formed in the base material formation board
  • the porous body may be formed such that the base material is disposed on the porous body, or the base material may be formed so that the porous body is embedded. Moreover, you may arrange
  • the gelation of the porous body can be performed according to a known method. That is, it can carry out according to the gelation method of each material.
  • the adhesion process involves electrolytic polymerization in an electrolyte solution containing a conductive monomer to form a conductive polymer adhesive layer from the conductive base material in the porous body, thereby forming the base material and the porous material. This is a process of bonding the body.
  • the conductive polymer monomer include 3,4-ethylenedioxythiophene (hereinafter sometimes referred to as EDOT), acetylene, pyrrole, thiophene, bithiophene, isothiophene, dodecylthiophene, and isonitethiophene.
  • the conductive polymer is electropolymerized by dissolving the monomer in a solvent, adding it to the porous gel, and applying a potential to the substrate.
  • concentration of the monomer in the solvent can be appropriately determined.
  • concentration can be 1 to 500 mM, and preferably 10 to 100 mM.
  • the potential applied in the electropolymerization can also be determined as appropriate, but is preferably 0.5 to 1.5V.
  • a peeling process is a process of peeling a base material from the board
  • the bonding force between the Au electrode and the porous body in the bonding step is more than the bonding between the Au electrode and the glass substrate. Since it is strong, the composite material can be peeled from the glass substrate by peeling the porous body from the glass substrate.
  • a metal electrode, carbon electrode, or stretchable electrode having a strong bond with the glass substrate for example, polyvinyl alcohol is applied to the glass substrate in advance to form an electrode pattern to facilitate peeling. be able to.
  • Conductive polymer polymerization layer forming step In the conductive polymer polymerization layer forming step, an electrolyte solution containing a conductive polymer monomer is brought into contact with the surface of the base material, and the base material surface is electrically conductive by electrolytic polymerization. This is a step of forming a conductive polymer polymerization layer. In this step, the monomer is dissolved in a solvent and brought into contact with the substrate surface. Then, by applying a voltage to the conductive substrate, the conductive polymer is polymerized on the substrate surface.
  • the concentration of the monomer can be determined as appropriate, and can be, for example, 1 to 500 mM, and preferably 10 to 100 mM.
  • the amount of solvent relative to the volume to be used can also be determined as appropriate.
  • the potential applied in the electropolymerization can also be determined as appropriate, but is preferably 0.5 to 1.5V.
  • the conductive polymer monomer used in this step the conductive polymer monomer used in the bonding step can be used.
  • the method for producing a composite material includes (1) a polymerization initiation part introduction step for introducing a polymerization initiation part on the surface of a substrate, and (2) a monomer in the porous body. A monomer impregnation step, and (3) a polymerization step in which a monomer polymerization reaction is performed using the polymerization start portion as a polymerization start point.
  • the kind of monomer polymerization reaction in the method for producing a composite material of the present embodiment is not particularly limited, but is preferably a radical polymerization reaction.
  • As the substrate, an insulating substrate, a conductive substrate, or a combination thereof can be used.
  • the polymerization initiator includes alkylphenone type (Irgacure (registered trademark) series), acylphosphine oxide type, intramolecular hydrogen abstraction type, other types such as oxime ester, benzoin ether such as isobutyl benzoin ether and isopropyl benzoin ether Type, benzyl ketal type such as benzyl methyl ketal and hydroxycyclohexyl phenyl ketone, and ketone type such as benzophenone and 2-chlorothioxanthone. These may be used alone or in combination of two or more.
  • alkylphenone type Irgacure (registered trademark) series
  • acylphosphine oxide type intramolecular hydrogen abstraction type
  • other types such as oxime ester
  • benzoin ether such as isobutyl benzoin ether and isopropyl benzoin ether
  • benzyl ketal type such as benzyl
  • the polymerization initiation part In the introduction of the polymerization initiation part, ozone treatment (carboxyl group introduction), oxygen plasma treatment, corona discharge treatment, UV treatment (for example, introduction of benzophenone), treatment with a silane coupling agent, treatment with a thiol compound, etc. are used.
  • the polymerization initiation part may be directly introduced by the treatment of the substrate surface, and the polymerization initiation part is further bonded after the treatment, for example, via an ester bond or an amide bond. May be.
  • the above-mentioned base material for example, polyurethane
  • the above-mentioned base material for example, polyurethane
  • ozone to introduce carboxyl groups on the base material surface
  • this carboxyl An ⁇ -hydroxyalkylphenone having a hydroxyl group can be bound to the group using a condensing agent.
  • benzophenone is applied to the surface of the base material (for example, polypropylene) placed on a flat plate, and then the base material after application is irradiated with ultraviolet rays to introduce a benzophenone portion on the surface of the base material. be able to.
  • the porous body is then impregnated with the monomer.
  • a monomer that can become a polymer and become an insulating polymer is used as the monomer.
  • the hydrogel can be impregnated in the monomer aqueous solution.
  • the porous body is a polymer hydrogel
  • the polymer hydrogel is once impregnated with water to wash (remove) complications such as by-products of the polymerization reaction and residual monomers. Later, the aqueous monomer solution can be impregnated.
  • the monomer may be a monomer that can become a polymer and become an insulating polymer, or a monomer that can become a polymer and become a conductive polymer.
  • the monomer that can be an insulating polymer may be a monomer that constitutes the above-mentioned insulating polymer.
  • (meth) acrylic acids such as acrylic acid, methacrylic acid, acrylic acid / alkyl methacrylate, and salts thereof; polyethylene Glycol di (meth) acrylate (PEGDA, PEGDM), hydroxyethyl methacrylate, acrylamide, N, N-dimethylacrylamide, 2-acrylamido-2-methylpropanesulfonic acid, N-isopropylacrylamide, vinylpyrrolidone, styrenesulfonic acid, ethylene glycol , Maleic anhydride, alkylene oxide, methyl vinyl ether-alt-maleic anhydride, N-vinylacetamide, starch, silanol, and the like. From (swelling degree at a temperature and pH and the like do not change) that, acrylamide, N, N-dimethylacrylamide, PEGDA, PEGDM
  • a monomer polymerization reaction is further performed using the polymerization start part as a polymerization start point.
  • the initiation reaction of monomer polymerization include thermal reaction, photoreaction, and oxidation-reduction reaction, and photoreaction is preferable from the viewpoint of ease of reaction control. These may be used alone or in combination of two or more.
  • the conditions for the polymerization initiation reaction can be appropriately determined according to the characteristics of the polymerization initiation portion.
  • the conditions for the polymerization reaction can be appropriately determined according to the characteristics of the monomer.
  • Example 1 Manufacture of a composite material for biological fixation having a convex part >> Using a cutting machine, a convex shape array mold was prepared on an acrylic plate. The shape of the convex structure was a cone, and the size was a bottom diameter of 250 ⁇ m and a height of 600 ⁇ m.
  • Prepolymer solution of double network hydrogel (10 mg / mL gellan gum (manufactured by Wako Pure Chemical Industries), 180 mg / mL acrylamide (manufactured by Wako Pure Chemical Industries), 0.118 mg / mL N, N′-methylenebisacrylamide (MBAA, manufactured by Wako Pure Chemical Industries, Ltd.) ) 2 mg / mL Irgacure 2959 (manufactured by BASF) and 10 mM CaCl 2 ⁇ 2H 2 O (manufactured by Wako Pure Chemical Industries, Ltd.) were prepared and poured into the mold. Next, after cooling at 4 ° C.
  • FIG. 1a is a photomicrograph of the flattened dry sample surface.
  • artificial cerebrospinal fluid Art Celebrity, manufactured by Otsuka Pharmaceutical Co., Ltd.
  • Example 2 Production of composite electrode body for biological fixation having a wound portion >> (1) Preparation of composite electrode body 1.0M 2-acrylamide-2-methyl-1-propanesulfonic acid sodium salt (NaAMPS, monomer, manufactured by Sigma Aldrich), 40 mM MBAA (crosslinking agent), and 1 mM 2-oxoglutaric acid (light Polymerization initiator: manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 10 g of distilled water to prepare a 1st prepolymer solution. Next, two glass plates were bonded together through a silicone spacer having an arbitrary thickness, and the 1st prepolymer solution was filled in the gap.
  • NaAMPS 2-acrylamide-2-methyl-1-propanesulfonic acid sodium salt
  • MBAA crosslinking agent
  • 1 mM 2-oxoglutaric acid light Polymerization initiator: manufactured by Wako Pure Chemical Industries, Ltd.
  • the 1st PNaAMPS hydrogel was immersed in a 2nd prepolymer solution for 2 days and then irradiated with 365 nm UV (intensity 1 mW / cm 2 ) for 6 hours in a glove box filled with nitrogen to obtain a double network hydrogel.
  • the hydrogel was washed overnight with distilled water.
  • the slide glass was cut into an appropriate size, and ultrasonically washed with acetone (manufactured by Wako Pure Chemical Industries), 86% ethanol-isopropanol (manufactured by Wako Pure Chemical Industries), and distilled water in this order for 15 minutes, and stored in isopropanol.
  • a 10% by weight polyvinyl alcohol aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd.) was spin-coated (1000 rpm, 20 seconds, ACT-220DII, manufactured by Active) on a slide glass, and a 100 ° C. hot plate (TH-900, manufactured by ASONE) was used. The solvent was evaporated by heating the substrate to form a polyvinyl alcohol sacrificial layer.
  • a polymerization solution 2 mL of 1-butanol (manufactured by Wako Pure Chemical Industries), 0.22 mL of 1M EDOT monomer solution (Crevios MV2, manufactured by Heraeus), 1-butanol solution (Clevios C containing 400 mM p-toluenesulfonic acid iron (III)) -B40V2, Heraeus) 6.5mL (EDOT oxidizing agent, dopant ion), 10% polyurethane (AR650, Okada Engineering) / tetrahydrofuran (Wako Pure Chemical) solution 22.5mL, anisole (Wako Pure Chemical) , For solvent evaporation suppression) was prepared by mixing 4.17 mL.
  • a conductive urethane film was formed by heating for 10 minutes on a hot plate at 100 ° C. to promote the evaporation of the solvent and the progress of the polymerization reaction.
  • the film was processed into an arbitrary pattern with a laser processing machine (manufactured by Versa LASER).
  • a double network gel was placed on the conductive urethane pattern substrate.
  • the polymerization solution was prepared by adding EDOT monomer to 50 mM and LiClO4 (manufactured by Wako Pure Chemicals, dopant ion) to 100 mM in distilled water. 0.5 mL of the polymerization solution is dropped on the porous body, and a potential of 1.0 V (vs.
  • Ag / AgCl is applied to the conductive urethane and the polymerization solution to carry out electrolytic oxidation polymerization with a polymerization amount of 300 mC / cm 2 . It was. After PEDOT polymerization, the substrate was immersed in distilled water at 100 ° C. for 30 minutes to dissolve the polyvinyl alcohol sacrificial layer. The double network gel was peeled from the substrate to obtain a double network gel substrate electrode body on which conductive urethane was patterned.
  • UV (wavelength 365 nm, 350 mW / cm 2 , 10 seconds, LC8, manufactured by Hamamatsu Photonics) was irradiated to gel the polymerization solution on the back surface of the electrode adhesion surface.
  • the inner diameter of the wound portion was controlled.
  • the obtained gel was removed from the mold and washed by immersing it in distilled water.
  • PNaAMPS polymerized on one surface of the composite electrode body swells due to the action of osmotic pressure, thereby deforming into a cylindrical shape.
  • a nylon mesh, a slide glass, and a weight were placed on the surface and dried in an oven at 70 ° C.
  • FIG. 2a is a photomicrograph of the flattened dry sample surface. When this was immersed in artificial cerebrospinal fluid (Art Celebrity, manufactured by Otsuka Pharmaceutical Co., Ltd.) for 5 minutes and swollen, it could be transformed into a cylindrical structure as shown in FIG. 2b.
  • FIG. 2c is a photograph of the composite electrode body for biological fixation wound around a glass rod.
  • FIG. 2d is a photograph of a composite electrode body for biological fixation wound around a sciatic nerve bundle collected from a rat.
  • FIG. 2e is a continuous photograph when the composite electrode body for biological fixation is wound around a glass rod.
  • an LED and a conductive tape connected in series with an external power source were affixed in advance, and a circuit was formed so that the LED flickered when the bio-fixing composite electrode body was wrapped and adhered.
  • a wound portion was formed in 8 minutes, the LED flashed, and adhesion was confirmed.
  • FIG. 2 f shows the relationship between the number of surface modifications and the inner diameter of the wound portion.
  • the surface modification is deformed only up to the arc shape, but after the second surface modification, it is deformed into a cylindrical shape as shown in the photograph inserted in the figure, and the inner diameter can be controlled from 5 mm to 1 mm by repeating the surface modification. there were.
  • FIG. 2g is a set-up schematic diagram of the measurement of the clamping pressure and the measurement result.
  • a silicone tube (outer diameter 3.1 mm) filled with water was prepared, one end of which was connected to a valve, and the other end was connected to a water pressure sensor (GP-M001, manufactured by Keyence Corporation).
  • the internal pressure of the tube was increased by the tightening pressure, and the internal pressure was measured with a water pressure sensor.
  • the tightening pressure increased with a decrease in the inner diameter of the wound portion, and when the biofixed composite electrode body with an inner diameter of 1 mm was wound around a tube with an outer diameter of 3.1 mm, the tightening pressure was 300 Pa.
  • the pressure that causes damage to the fragile nerve bundle is 1.3 kPa (Non-patent Document 2). Therefore, it was shown that this electrode can be safely and closely wound around the nerve bundle.
  • Example 3 Manufacture of an electrode composite material for biological fixation having a clamping part >> A double network hydrogel was prepared by the method described in Example 2 (1). A silicone rubber vessel filled with the PNaAMPS polymerization solution described in Example 2 (2) was prepared, and a double network hydrogel was placed on the surface thereof. Further, the other part was covered with a shielding plate so that only the central part of the double network hydrogel was exposed. UV (wavelength 365 nm, 350 mW / cm 2 , 10 seconds) was irradiated to gel the polymerization solution. The obtained gel was removed from the mold and washed by immersing it in distilled water.
  • UV wavelength 365 nm, 350 mW / cm 2 , 10 seconds
  • FIG. 3a is a photomicrograph of the flattened dry sample surface.
  • the T-shaped structure in the vicinity is an agarose gel produced as a target to be sandwiched.
  • the composite material for biological fixation of the present invention can be used as an electrode or a sensor that can be easily and stably fixed to a target mounting site in a living body.

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Abstract

La présente invention vise à fournir un matériau composite qui peut être implanté facilement et de manière stable dans un site d'implantation cible. Le matériau composite à implanter dans un organisme vivant est obtenu en joignant un substrat et un corps poreux l'un à l'autre, et est caractérisé en ce que la structure d'implantation dans un organisme vivant est choisie dans le groupe constitué par une partie enroulement, une partie de prise en sandwich, une partie en saillie et une partie ventouse.
PCT/JP2017/013394 2016-03-30 2017-03-30 Matériau composite pour implantation dans un organisme vivant WO2017170929A1 (fr)

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Cited By (3)

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Publication number Priority date Publication date Assignee Title
CN109350847A (zh) * 2018-11-29 2019-02-19 深圳先进技术研究院 一种功能化植入式柔性电极及其应用
WO2020189479A1 (fr) * 2019-03-19 2020-09-24 東レ株式会社 Feuille conductrice
CN112708148A (zh) * 2020-12-24 2021-04-27 江西科技师范大学 一种应用于太阳能水净化的导电聚合物水凝胶的制备方法

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JP2014516696A (ja) * 2011-05-19 2014-07-17 ニューロス・メディカル・インコーポレイティッド 高周波電気神経ブロック
WO2014157550A1 (fr) * 2013-03-28 2014-10-02 国立大学法人東北大学 Corps d'électrode à substrat poreux et son procédé de fabrication
JP2017086824A (ja) * 2015-11-17 2017-05-25 日本電信電話株式会社 生体適合性ゲル材料、生体適合性ゲル材料の製造方法、生体適合性ゲル電極、及び生体組織吸着デバイス

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
JP2014516696A (ja) * 2011-05-19 2014-07-17 ニューロス・メディカル・インコーポレイティッド 高周波電気神経ブロック
WO2014157550A1 (fr) * 2013-03-28 2014-10-02 国立大学法人東北大学 Corps d'électrode à substrat poreux et son procédé de fabrication
JP2017086824A (ja) * 2015-11-17 2017-05-25 日本電信電話株式会社 生体適合性ゲル材料、生体適合性ゲル材料の製造方法、生体適合性ゲル電極、及び生体組織吸着デバイス

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109350847A (zh) * 2018-11-29 2019-02-19 深圳先进技术研究院 一种功能化植入式柔性电极及其应用
WO2020189479A1 (fr) * 2019-03-19 2020-09-24 東レ株式会社 Feuille conductrice
CN113613902A (zh) * 2019-03-19 2021-11-05 东丽株式会社 导电性片材
CN113613902B (zh) * 2019-03-19 2023-08-18 东丽株式会社 导电性片材
CN112708148A (zh) * 2020-12-24 2021-04-27 江西科技师范大学 一种应用于太阳能水净化的导电聚合物水凝胶的制备方法

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