WO2016190202A1 - 筒状織物構造体 - Google Patents
筒状織物構造体 Download PDFInfo
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- WO2016190202A1 WO2016190202A1 PCT/JP2016/064811 JP2016064811W WO2016190202A1 WO 2016190202 A1 WO2016190202 A1 WO 2016190202A1 JP 2016064811 W JP2016064811 W JP 2016064811W WO 2016190202 A1 WO2016190202 A1 WO 2016190202A1
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- WIPO (PCT)
- Prior art keywords
- acid
- blood vessel
- artificial blood
- woven fabric
- tubular
- Prior art date
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- D—TEXTILES; PAPER
- D03—WEAVING
- D03D—WOVEN FABRICS; METHODS OF WEAVING; LOOMS
- D03D3/00—Woven fabrics characterised by their shape
- D03D3/02—Tubular fabrics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
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- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
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- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
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- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
- A61L33/0041—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate characterised by the choice of an antithrombatic agent other than heparin
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/068—Use of macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- D—TEXTILES; PAPER
- D03—WEAVING
- D03D—WOVEN FABRICS; METHODS OF WEAVING; LOOMS
- D03D11/00—Double or multi-ply fabrics not otherwise provided for
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- D—TEXTILES; PAPER
- D03—WEAVING
- D03D—WOVEN FABRICS; METHODS OF WEAVING; LOOMS
- D03D15/00—Woven fabrics characterised by the material, structure or properties of the fibres, filaments, yarns, threads or other warp or weft elements used
- D03D15/20—Woven fabrics characterised by the material, structure or properties of the fibres, filaments, yarns, threads or other warp or weft elements used characterised by the material of the fibres or filaments constituting the yarns or threads
- D03D15/283—Woven fabrics characterised by the material, structure or properties of the fibres, filaments, yarns, threads or other warp or weft elements used characterised by the material of the fibres or filaments constituting the yarns or threads synthetic polymer-based, e.g. polyamide or polyester fibres
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- D—TEXTILES; PAPER
- D03—WEAVING
- D03D—WOVEN FABRICS; METHODS OF WEAVING; LOOMS
- D03D15/00—Woven fabrics characterised by the material, structure or properties of the fibres, filaments, yarns, threads or other warp or weft elements used
- D03D15/30—Woven fabrics characterised by the material, structure or properties of the fibres, filaments, yarns, threads or other warp or weft elements used characterised by the structure of the fibres or filaments
- D03D15/33—Ultrafine fibres, e.g. microfibres or nanofibres
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- D—TEXTILES; PAPER
- D03—WEAVING
- D03D—WOVEN FABRICS; METHODS OF WEAVING; LOOMS
- D03D15/00—Woven fabrics characterised by the material, structure or properties of the fibres, filaments, yarns, threads or other warp or weft elements used
- D03D15/50—Woven fabrics characterised by the material, structure or properties of the fibres, filaments, yarns, threads or other warp or weft elements used characterised by the properties of the yarns or threads
- D03D15/56—Woven fabrics characterised by the material, structure or properties of the fibres, filaments, yarns, threads or other warp or weft elements used characterised by the properties of the yarns or threads elastic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/0077—Special surfaces of prostheses, e.g. for improving ingrowth
- A61F2002/009—Special surfaces of prostheses, e.g. for improving ingrowth for hindering or preventing attachment of biological tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0076—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof multilayered, e.g. laminated structures
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
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- D—TEXTILES; PAPER
- D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B2331/00—Fibres made from polymers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polycondensation products
- D10B2331/04—Fibres made from polymers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polycondensation products polyesters, e.g. polyethylene terephthalate [PET]
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- D—TEXTILES; PAPER
- D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B2401/00—Physical properties
- D10B2401/06—Load-responsive characteristics
- D10B2401/061—Load-responsive characteristics elastic
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- D—TEXTILES; PAPER
- D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B2509/00—Medical; Hygiene
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- D—TEXTILES; PAPER
- D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B2509/00—Medical; Hygiene
- D10B2509/06—Vascular grafts; stents
Definitions
- the present invention relates to a multi-tubular fabric structure. More specifically, the present invention relates to a multi-tubular woven structure useful for fluids, powder transfer and hose for protecting linear objects such as wires, cables, and conduits, tubular filters, artificial blood vessel substrates, and the like. *
- Cylindrical fiber structures are used in various industrial applications such as hoses, reinforcing materials, protective materials, artificial blood vessels, etc., but they can be bent, spirally wound, or used in accordance with the space used. It takes a shape such as being arranged in a meandering manner. Therefore, means for improving the kink resistance (easiness of bending) has been proposed so that the above-described tubular fiber structure has a shape that matches the usage situation, and does not cause crushing or twisting.
- a fabric sleeve having a shape (Patent Document 1) has been proposed.
- a tubular body has been proposed in which the inner surface of a tubular fabric that can be used as a watertight seal or a packing member of a shield excavator is hermetically treated with rubber or resin (Patent Document 2). It is a medical device used to replace pathological biological blood vessels such as sclerosis, or to form a bypass or a shunt.
- fabric-made artificial blood vessels made of woven fabric can be used for vascular surgical operations such as aorta, which are in high demand, because the fiber gap can be reduced and the amount of blood leakage can be reduced compared to artificial blood vessels made of knitted fabrics. It has been.
- a method of reducing the amount of blood leakage a method of densifying the fiber gap is common, but the resulting artificial blood vessel becomes hard due to an increase in fiber density.
- an alternative pathological biological blood vessel that is, a biological blood vessel that is anastomosed with the artificial blood vessel is also affected by arteriosclerosis and the like, and thus surgery is often difficult.
- Patent Document 3 As a method for increasing the flexibility of a cloth-made artificial blood vessel, an artificial blood vessel using an elastic fiber having high stretch properties has been reported (Patent Document 3). Since the fiber diameter is large, there is a problem that blood is likely to leak from the fiber gap.
- Patent Document 4 A method of filling and preventing blood leakage has been reported (Patent Document 4).
- in vivo blood vessels have an intima on the inner surface, and having vascular endothelial cells can inhibit thrombus formation.
- conventional artificial blood vessels have low cytophilicity, and vascular endothelial cells are established. Not only is it difficult, it takes time to establish vascular endothelial cells and to form the intima. Therefore, not only the antithrombotic properties immediately after transplantation but also a function that exhibits cell affinity over time has been required.
- Patent Documents 7 to 10 As a method of imparting cell affinity to a cloth artificial blood vessel, there is a method of making the fiber structure a structure that promotes cell proliferation and infiltration, a method of optimizing the fiber diameter, napped, fluff and / or loop-like fibers (Patent Documents 7 to 10) have been reported.
- the living body recognizes this as a foreign substance, and in particular, the blood coagulation reaction proceeds on the contact surface with the blood of the artificial blood vessel, that is, the inner surface, thereby forming a thrombus. is needed.
- heparin or a heparin derivative cannot be directly applied to a medical material made of cloth such as polyester fiber constituting an artificial blood vessel or a medical material made of expanded porous polytetrafluoroethylene (hereinafter, “ePTFE”). Therefore, after modifying the surface of the medical material, heparin or heparin derivative is imparted to the surface of the material by covalent bond (Patent Documents 11 to 13), or heparin or heparin derivative is imparted to the surface of the material by ionic bond. (Patent Documents 14 to 17) have been reported.
- Patent Documents 6 and 18 As a method of imparting antithrombogenicity to a cloth artificial blood vessel, a method in which heparin or a heparin derivative is included in a gel such as collagen or gelatin absorbed in vivo used to prevent blood leakage and imparted to the surface of the material.
- Patent Documents 6 and 18 a method in which heparin or a heparin derivative is included in a gel such as collagen or gelatin absorbed in vivo used to prevent blood leakage and imparted to the surface of the material.
- Patent Document 19 Patent Document 19
- in vivo blood vessels have an intima on the inner surface, and having vascular endothelial cells can inhibit thrombus formation.
- conventional artificial blood vessels have low cytophilicity, and vascular endothelial cells are established. Not only is it difficult, it takes time to establish vascular endothelial cells and to form the intima. Therefore, not only the antithrombotic properties immediately after transplantation but also a function that exhibits cell affinity over time has been required.
- Japanese Patent No. 2718571 JP 2003-329146 A Japanese Patent Laid-Open No. 8-80342 Japanese Patent No. 3799626 Japanese Patent Publication No. 5-48132 Japanese Patent Publication No. 5-88611 Japanese Examined Patent Publication No. 61-4546 Japanese Examined Patent Publication No. 61-58190 Japanese Patent Publication No. 63-52898 Japanese Patent Publication No. 5-28143 Special table 2009-545333 gazette Japanese Patent No. 4152075 Japanese Patent No. 3497612 Japanese Patent Publication No. 60-41947 Japanese Patent Publication No. 60-47287 Japanese Patent No. 4273965 JP-A-10-151192 Japanese Patent Publication No.8-24686 JP-A-7-265338 Japanese Patent No. 4461217 WO08 / 032758 WO12 / 176661
- Patent Document 2 also needs to be water-tightened on the inner surface because leakage occurs when the fluid or powder is transferred.
- the method disclosed in Patent Document 3 when used for artificial blood vessels, as a measure against blood leakage, when the method disclosed in Patent Document 3 is used for artificial blood vessels made of cloth, collagen or gelatin containing heparin or a heparin derivative applied to the fiber surface is coated. There was a need.
- Patent Document 5 in order to promptly establish vascular endothelial cells on the inner surface of an artificial blood vessel and promote the formation of the intima, Patent Document 6 describes a biocompatible material with fewer in vitro foreign substances.
- a method of making an artificial blood vessel into a high-porosity structure that is, a highly permeable woven structure is disclosed, but pre-clotting is indispensable, and the thrombus formed by the operation has a fiber diameter or fiber. Since the fine structure such as the gap is lost, the cell affinity is lowered.
- anticoagulants eg, heparin, argatroban, etc.
- heparin heparin, argatroban, etc.
- the fiber gap may not be sufficiently filled by pre-crotting.
- the blood fibrinolysis system in the blood after the operation may dissolve the thrombus generated by preclotting, leading to blood leakage.
- nap, fluff and / or loop-like fibers are used in an artificial blood vessel having a cell affinity of 0.5 denier, that is, 0.56 dtex or less for at least part of the inner surface.
- a method for enhancing cell affinity by imparting is disclosed, there is a need for an additional step for forming napped hairs, fluff and / or looped fibers, and a problem that fiber waste may be generated by the additional step was there.
- the warp and weft yarns are more disturbed in the fiber direction, there is a problem that the vascular endothelial cells are hardly fixed and the cell affinity is lowered.
- Patent Documents 11 to 13 describe a method in which a surface modifier and heparin or a heparin derivative are covalently bonded or ionically bonded to a surface of a medical material, but a cloth artificial blood vessel is described. In addition, a tubular fabric having elasticity and flexibility is not used as a base material.
- Patent Documents 18 and 19 describe a method of physically imparting an antithrombotic material dissolved in a gel or organic solvent containing heparin or a heparin derivative to the surface of a medical material.
- a gel or organic solvent containing heparin or a heparin derivative to the surface of a medical material.
- the fiber diameter for promoting cell proliferation of the artificial blood vessel made of cloth is no description of the fiber diameter for promoting cell proliferation of the artificial blood vessel made of cloth.
- a stretchable and flexible tubular fabric is not used as the base material.
- Patent Documents 20 to 22 describe two compounds having both antiplatelet adhesion performance and antithrombin activation performance on the surface of a medical material, and performance of both antiplatelet adhesion performance and antithrombin activation performance. Although a method for immobilizing a monomolecular compound is described, a tubular fabric having elasticity and flexibility is not used as a base material.
- the present invention has been made in view of such problems of the prior art, and its purpose is excellent in mechanical properties such as mechanical strength, mechanical properties such as elasticity and flexibility, and physical properties such as kink resistance.
- the artificial blood vessel made of cloth that has a small amount of blood leakage and can achieve both antithrombogenicity and cell affinity
- the purpose is to provide.
- tubular woven fabric structure according to any one of (1) to (5), wherein the tubular woven fabric structure is composed of two or more layers.
- water permeability on the inner surface of the tubular woven structure is 500 mL (milliliter) / min / 120 mmHg (16 kPa) / cm 2 or less. body.
- An artificial blood vessel using the tubular woven fabric structure according to any one of (1) to (8) as a base material.
- the abundance ratio of nitrogen atoms to the abundance of all atoms on the inner surface measured by X-ray photoelectron spectroscopy (XPS) is 6.0 to 12.0 atomic%.
- the antithrombotic material includes a cationic polymer including, as a constituent monomer, a compound selected from the group consisting of alkyleneimine, vinylamine, allylamine, lysine, protamine, and diallyldimethylammonium chloride, and the cationic polymer includes The artificial blood vessel according to any one of (10) to (13), which is covalently bonded to a warp and a weft constituting a tubular woven fabric.
- the antithrombotic material is composed of a compound selected from the group consisting of ethylene glycol, propylene glycol, vinyl pyrrolidone, vinyl alcohol, vinyl caprolactam, vinyl acetate, styrene, methyl methacrylate, hydroxyethyl methacrylate and siloxane as a constituent monomer.
- a compound containing three kinds of skeleton structures comprising a skeleton structure of a hydrophilic polymer, a skeleton structure of 4- (aminomethyl) benzenecarboximidamide or benzeneamidine, and a skeleton structure of methoxybenzenesulfonic acid amide,
- the artificial blood vessel according to (15), wherein the compound containing the three types of skeleton structures is any one of compounds represented by the following general formulas (I) to (IV).
- n and o represent an integer of 0 to 4
- n represents an integer of 3 to 1000
- n ′ represents an integer of 3 to 1000
- X represents a functional group selected from the group consisting of a hydroxyl group, a thiol group, an amino group, a carboxyl group, an aldehyde group, an isocyanate group, and a thioisocyanate group.
- the antithrombotic material is an anionic polymer containing a compound selected from the group consisting of acrylic acid, methacrylic acid, ⁇ -glutamic acid, ⁇ -glutamic acid, and aspartic acid as a constituent monomer, or oxalic acid, malonic acid
- Anionic compounds selected from the group consisting of succinic acid, fumaric acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, malic acid, tartaric acid and citric acid )
- the artificial blood vessel according to any one of the above.
- mechanical properties such as mechanical strength, stretchability and flexibility, physical properties such as kink resistance, etc. can be transferred without problems, and fluids and powders can be transferred without problems.
- This is a tubular woven fabric structure that can be suitably used as a substrate for hoses for protecting linear objects, fluid transfer hoses, tubular filters, packings, and artificial blood vessels.
- the amount of blood leakage is small, and it is possible to achieve both antithrombogenicity and cell affinity.
- the anti-thrombotic material layer having an appropriate thickness according to claim 10 it is possible to achieve optimal anti-thrombogenicity.
- the tubular woven fabric structure of the present invention is a woven fabric woven in a cylindrical shape by crossing warps and wefts, and an elastic fiber having a single yarn fineness of 1.0 dtex or more is used for at least a part of the warp, It is characterized by using a microfiber having a single yarn fineness of less than 1.0 dtex for at least a part of the weft.
- the cylindrical woven fabric is a woven fabric obtained by crossing warps and wefts into a cylindrical shape.
- at least a part of the warp has a single yarn fineness of 1.0 dtex.
- the above-described elastic fibers are characterized in that microfibers in which at least part of the wefts have a single yarn fineness of less than 1.0 dtex are used.
- the single yarn fineness is a value obtained by measuring the fineness fineness at a predetermined load of 0.045 cN / dtex according to JIS L 1013 (2010) 8.3.1 A method as the total fineness. A numerical value calculated by dividing by a number.
- At least a part of the warp contains an elastic fiber having a single yarn fineness of 1.0 dtex or more
- an elastic fiber having a single yarn fineness of 1.0 dtex or more in at least a part of the warp, not only the mechanical strength of the tubular woven fabric structure is improved, but also a stretchable and flexible tubular woven fabric, Physical properties such as kink resistance can also be improved. If the warp does not contain elastic fibers having a single yarn fineness of 1.0 dtex or more, not only the mechanical strength of the tubular woven fabric but also the stretchability and flexibility tend to decrease.
- the warp contains an elastic fiber having a single yarn fineness of 2.0 dtex or more.
- the single yarn fineness is preferably 5.0 dtex or less, more preferably 3.0 dtex or less.
- a multifilament composed of a plurality of single yarns can be preferably used for the warp.
- the number of filaments constituting the multifilament is not particularly limited, but is preferably 5 or more, and more preferably 15 or more.
- the total fineness of the elastic fiber is preferably 5 dtex or more and 200 dtex or less.
- the fibers are not too thin, and sufficient strength and stretchability can be obtained.
- the fiber is not too thick by being 200 dtex or less, and excellent flexibility can be imparted to the tubular woven fabric structure.
- the elastic fiber used in the present invention is a fiber having stretchability (high elongation rate and elongation recovery rate), and is not particularly limited, but when the yarn is stretched by 20% (elongation rate: 20%).
- the elongation recovery rate is 30% or more, more preferably 40% or more, more preferably 50% or more, the elongation recovery rate when 10% is extended (elongation rate 10%) is 50% or more, Preferably it is 60% or more, more preferably 80%.
- the upper limit of the elongation recovery rate is 20% elongation (elongation rate 20%).
- the recovery rate is preferably 90% or less.
- Preferable specific examples include spandex fibers and composite cross-section fibers composed of two types of polymers having different heat shrinkage characteristics.
- spandex fiber a normal elastic yarn called a so-called spandex fiber such as a polyurethane fiber can be used.
- spandex fibers are preferably used as a covering yarn obtained by using a core yarn and covering a synthetic fiber such as a nylon fiber or a polyester fiber as a sheath yarn.
- the composite cross-sectional fiber composed of two types of polymers having different heat shrinkage characteristics
- the composite fiber is provided with latent crimps by using two types of polymers having different heat shrinkage characteristics.
- this composite cross-section fiber is used with the form of the multifilament comprised from a some filament.
- the composite form is a composite cross-section fiber in which two types of polymer components having different heat shrinkage properties are combined in a side-by-side type or an eccentric core-sheath type along the fiber length direction, thereby providing a latent crimp.
- a cross-sectional fiber is preferable.
- Such a composite cross-section fiber can be a multifilament imparted with high stretchability by expressing coil crimping by false twisting or heat treatment.
- the elastic fiber used in the present invention is preferably a composite cross-sectional fiber composed of two types of polymers having different heat shrinkage characteristics. Among them, two types of polymer components having different heat shrinkage characteristics are arranged along the fiber length direction. Multifilaments of composite cross-section fibers compounded into side-by-side or eccentric core-sheath types, and more preferably imparts high stretchability by developing coil crimps by false twisting or heat treatment as multifilaments of such composite fibers Use multifilaments.
- tubular woven fabric structure of the present invention it is preferable to use elastic fibers at least 50% or more of the number of warps. More preferably, it is 80% or more, and most preferably 100%.
- At least a part of the weft contains a microfiber having a single yarn fineness of less than 1.0 dtex
- a microfiber having a single yarn fineness of less than 1.0 dtex By including microfibers having a single yarn fineness of less than 1.0 dtex in at least a part of the weft yarn, not only the flexibility of the tubular woven fabric structure is improved, but the single yarn is thin and the gap between the single yarns can be reduced. Therefore, it is possible to reduce water permeability.
- the microfiber refers to a fiber having a single yarn fineness of less than 1.0 dtex. Such microfibers are preferably used in the form of multifilaments.
- the water permeability can be lowered by increasing the weave density, but the tubular woven fabric structure becomes stiff and flexible and stretchable. Will be damaged. If the woven structure becomes hard, it is not preferable because it causes kinks and unevenness on the inner layer surface.
- the number of microfibers is not limited to one, and a plurality of types of microfibers having different single yarn fineness and total fineness can be combined.
- the so-called direct spinning type of microfiber obtained by so-called direct melt spinning may be used as it is, but the so-called split fiber type in which the single yarn of the split fiber type composite cross-section fiber is split to make it finer. Can also be used.
- the split fiber type can be formed into a fine fiber after forming a tubular woven fabric using a fiber that can be made fine by chemical or physical means, or can be formed into a tubular woven fabric after being made fine,
- the former is preferable from the point described below.
- one component of a multicomponent fiber is removed or exfoliated as a method of ultrafinening by chemical or physical means.
- various organic fibers can be used as the microfibers used for the wefts of the tubular woven fabric structure, but polyester is preferable from the viewpoint of water absorption and deterioration resistance.
- the polyester include fibers made of polyethylene terephthalate, polybutylene terephthalate, and the like. Further, it may be a fiber made of a copolyester obtained by copolymerizing polyethylene terephthalate, polybutylene terephthalate or the like with an aliphatic dicarboxylic acid such as isophthalic acid, 5-sodium sulfoisophthalic acid or adipic acid as an acid component.
- the combination of the fibers constituting the multifilament yarn and the fibers constituting the warp and weft may be the same or different, and can be combined as appropriate.
- the tubular woven fabric structure of the present invention is used for an artificial blood vessel, since the wefts contain microfibers having a single yarn fineness of less than 1.0 dtex, the inter-fiber voids are reduced and blood leakage can be further suppressed.
- the number of scaffolds suitable for attachment of vascular endothelial cells is extremely large, so that familiarity between vascular endothelial cells and artificial vascular inner layer constituent fibers is good, and the adhesion of vascular endothelial cells to the artificial vascular inner layer is good. Since it becomes favorable, an artificial blood vessel with high biocompatibility can be obtained.
- the microfiber used for the artificial blood vessel has a single yarn fineness of less than 1.0 dtex, and more preferably a single yarn fineness of 0.50 dtex or less. Moreover, if the single yarn fineness is 0.008 dtex or more, it is preferable in terms of excellent cell adhesion.
- the total fineness is preferably 5 dtex or more and 200 dtex or less. If the total fineness is less than 5 dtex, the fibers are too thin and sufficient strength cannot be obtained. On the other hand, if it exceeds 200 dtex, the fibers are too thick, and the flexibility of the tubular woven fabric structure is impaired.
- Platelets have the property of adhering to the surface when they come into contact with foreign substances other than the surface of vascular endothelial cells.
- the platelets When the degree of stimulation received from the foreign substance is large, the platelets are self-ruptured to release internal granules around them, and the platelet debris adheres to the original part. When this granule is scattered, other platelets to which it adheres are ruptured by stimulation by the granule, and further release the granules in a chain. And leave those debris.
- a thrombus grows in a state where these debris and granules gather and aggregate one after another.
- platelets Since the size of platelets is about 1 to 2 ⁇ m, platelets can easily adhere to microfibers with a single yarn fineness of less than 1.0 dtex, and thrombus grown by the mechanism described above adheres to ultrafine microfibers. To do. When platelet aggregation is initiated, fibrin deposition is also naturally induced, so that blood leakage can be effectively suppressed.
- the cover factor of the tubular woven fabric structure of the present invention is preferably warp cover factor Cfa ⁇ weft cover factor Cfb because the area occupied by the microfiber is large and the water permeability and blood leakage can be controlled low.
- the tubular woven fabric structure of the present invention has a multilayer structure of two or more layers
- a protective material for wires or electric wires It is particularly effective that the cover factor of the innermost layer in contact with the substance is the above relationship (Cfa ⁇ Cfb), and it can be preferably used even when the woven structure other than the innermost layer is not the above relationship (Cfa ⁇ Cfb).
- the cover factor is a value measured by the method described later.
- the cover factor of the warp is preferably 500 or more and 2000 or less, more preferably 1000 or more and 2000 or less.
- the cover factor of the weft yarn is preferably 1000 or more and 2000 or less.
- the total cover factor (Cfa + Cfb) represents the density of the entire tubular woven fabric structure, but the preferred range of the total cover factor (Cfa + Cfb) is 1500 or more and 4000 or less, more preferably 1800 or more. 3000 or less.
- the elongation at the time of 3.3 N / load per 1 mm width of the tubular woven structure in the longitudinal direction of the tubular woven structure is preferably 4% or more. % Or more is more preferable.
- the upper limit is preferably 15% or less, and more preferably 10% or less.
- the elongation at the time of 3.3 N / load per 1 mm width of the tubular fabric structure in the warp direction of the tubular fabric structure is measured by the method described later.
- the elongation at break of the tubular woven fabric structure is 50% or less, it is preferable because both dimensional stability and stretchability are compatible and excellent in flexibility, and more preferably 40% or less. Moreover, it is preferable that it is 10% or more from the point of a softness
- the tubular woven fabric structure of the present invention has a high elongation at low loads, and thus follows a small external force well, but has a small dimensional elongation and is excellent in dimensional stability.
- Such a feature is particularly preferable when used as a base material for an artificial blood vessel.
- autologous blood vessels biological blood vessels
- an elastic fiber is used for the warp, so that excellent stretchability is obtained, and the above-mentioned preferable range is achieved by appropriately adjusting the elongation rate, elongation recovery rate, warp cover factor, etc. of the elastic multifilament used.
- the elastic fiber having a single yarn fineness of 1.0 dtex or more constituting the warp is a composite cross-sectional fiber composed of two types of polymers having different heat shrinkage characteristics, the above excellent stretch properties are easily exhibited. Can do.
- polyesters having different heat shrinkage characteristics are preferably exemplified.
- polyesters having different viscosities for example, polytrimethylene terephthalate
- polytrimethylene terephthalate and other polymer esters for example, polyethylene terephthalate, polybutylene terephthalate
- one component is a polyester mainly composed of polyethylene terephthalate (PET) and the other component is a polyester mainly composed of polytrimethylene terephthalate (PTT).
- the above-mentioned two components are composed of fibers combined in a side-by-side type or an eccentric core-sheath type along the fiber length direction.
- Such composite yarn is preferably subjected to false twisting or heat treatment, so that coil crimp can be expressed, and thus excellent stretchability can be obtained.
- PTT is selected to have a high viscosity and PET to have a low viscosity.
- the diameter of the three-dimensional coil and the number of coils per unit fiber length are determined by the shrinkage difference between the high shrinkage component and the low shrinkage component (the value obtained by adding the elastic recovery rate difference and the heat shrinkage rate difference). As the shrinkage difference increases, the coil diameter decreases and the number of coils per unit fiber length increases.
- the low shrinkage component of the present invention is preferably PET.
- PET has the characteristics that interfacial adhesion with PTT, which is a highly shrinkable component, is extremely good, melt spinning is easy, and stable spinning can be performed even at high speed spinning exceeding 6000 m / min. Further, when PTT is spun at a high speed, there are problems such as winding tightness that makes it difficult for the package to come off, and deterioration in quality due to deterioration of yarn unevenness in the longitudinal direction of the yarn. On the other hand, winding tightening is eliminated by placing PET at a specific ratio or more in one component of the composite spinning, and quality deterioration with time of the wound package hardly occurs.
- the difference in shrinkage rate from the high viscosity component PTT can be easily controlled by the heat setting temperature in the drawing false twisting process.
- PTT has a small set temperature dependency of heat shrinkage
- PET has a large set temperature dependency of heat shrinkage. Therefore, when it is desired to increase the stretchability, the difference in thermal shrinkage between PTT and PET can be increased, and the set temperature in the stretch false twisting process can be increased. Conversely, when it is desired to lower the stretchability, the difference in shrinkage rate between PTT and PET may be reduced, and the heat setting temperature may be lowered.
- the PTT of the present invention is a polyester obtained using terephthalic acid as the main acid component and 1,3-propanediol as the main glycol component.
- the PET used in the present invention is a polyester obtained using terephthalic acid as the main acid component and ethylene glycol as the main glycol component.
- any component may include a copolymer component capable of forming another ester bond at a ratio of 20 mol%, more preferably 10 mol% or less.
- the copolymerizable compound include dicarboxylic acids such as isophthalic acid, succinic acid, cyclohexanedicarboxylic acid, adipic acid, dimer acid, sebacic acid, and 5-sodium sulfoisophthalic acid, ethylene glycol, propylene glycol, diethylene glycol, and dipropylene glycol.
- Diols such as butanediol, neopentyl glycol, cyclohexanedimethanol, polyethylene glycol, and polypropylene glycol are not limited thereto.
- the cylindrical woven fabric structure is composed of two or more layers
- the cylindrical fabric structure is composed of two or more layers, so that the innermost layer portion of the cylindrical fabric structure is protected from external force and durability is improved. This is preferable because it can prevent leakage of liquid and powder and can improve the function of protecting linear objects such as wires, cables and conduits.
- the inside is in contact with blood.
- the inner side of the tubular fabric in contact with blood is an inner layered tubular fabric
- the outer side of the cylindrical fabric forming the outer layer of the artificial blood vessel is an outer layered tubular fabric
- the outer layered tubular fabric It is preferable that a structure in which the inner layer tubular fabric is overlapped is a multiple tubular fabric structure.
- the multiple tubular woven fabric structure constituting the artificial blood vessel of the present invention may include a tubular woven fabric layer other than the inner tier tubular woven fabric and the outer tier tubular woven fabric, but when the number of the tubular woven fabric layers is too large.
- the number of the cylindrical fabric layers is preferably 2 to 4, more preferably 2 to 3.
- the number of layers of the tubular woven fabric structure of the present invention is not particularly limited, but from the viewpoint of stretchability and flexibility, the layers are integrally woven by means such as inner wall layer warp fastening, inner wall layer weft fastening, double weft fastening, etc.
- a double woven fabric structure is particularly preferred. Double weaving eliminates the need to laminate two fabrics together by laminating or sewing, as well as flexible and mechanical strength because the two layers are integrated with warp or weft. A tubular woven structure having a high height can be obtained.
- the weft in the case of a multi-layered structure of two or more layers is not particularly limited as long as at least a part of the weft is a microfiber having a single yarn fineness of less than 1.0 dtex.
- a fiber can be selected and used, and the form can be appropriately selected, such as a multifilament or a monofilament.
- microfibers having a single yarn fineness of less than 1.0 dtex are disposed on the inner layer surface side.
- a water jet room, an air jet room, a rapier room, a shuttle room, and the like can be used.
- a shuttle room which is excellent in weaving property in a cylindrical shape and can obtain a uniform cylindrical structure.
- a plain woven fabric, a twill woven fabric, a satin woven fabric, and a woven fabric such as a modified woven fabric or a multi-woven fabric can be used.
- a basic weaving method known means can be adopted.
- the tubular woven fabric structure of the present invention may be bent or serpentine. Since the tubular woven fabric structure of the present invention is excellent in kink properties, it is difficult for crushing and twisting to occur, but it is preferable to have further kink resistance (flexibility). For that purpose, it is preferable to use a monofilament having a thickness of 20 ⁇ m or more for at least a part of the wefts of the layers excluding the innermost layer.
- a weft consisting of a monofilament having a thickness of 20 ⁇ m or more with high rigidity is preferable because it gives the tubular woven fabric structure better kink resistance.
- a more preferable thickness is 100 ⁇ m or more.
- the upper limit is preferably 300 ⁇ m or less, more preferably 200 ⁇ m or less from the viewpoint of flexibility.
- polyester is preferable from the viewpoint of water absorption and deterioration resistance.
- the polyester include polyethylene terephthalate and polybutylene terephthalate.
- it may be a monofilament made of a copolyester obtained by copolymerizing an aliphatic dicarboxylic acid such as isophthalic acid, 5-sodium sulfoisophthalic acid or adipic acid as an acid component with polyethylene terephthalate, polybutylene terephthalate or the like.
- the monofilament which consists of a copolyester whose core is polyethylene terephthalate and whose sheath has a melting point lower than that of the core may be used.
- Monofilaments having a low melting point component in the sheath can be heat-set in post-processing and fused on the outer periphery of the tubular woven fabric structure to improve the stability of mechanical strength such as dimensional stability and kink resistance. Therefore, it can be preferably used.
- the water permeability on the inner surface is preferably 500 mL (milliliter) / min / 120 mmHg (16 kPa) / cm 2 or less, more preferably 200 mL / min / 120 mmHg / cm 2 or less. More preferably, it is still more preferably 150 mL / min / 120 mmHg / cm 2 or less.
- an artificial blood vessel using a general conventional tubular woven fabric it is difficult to achieve low water permeability only with a fiber gap, and an operation for imparting a gel such as collagen or gelatin absorbed in the living body was necessary.
- the fine structure such as the fiber diameter and fiber gap for promoting cell proliferation is lost, so that the cell affinity is lowered or absorbed in the living body.
- platelets adhere to gel such as gelatin to form thrombus.
- an artificial blood vessel having a small inner diameter of 6 mm or less relatively promotes thrombus formation.
- the tubular woven fabric structure of the present invention can achieve low water permeability as described above.
- the lower limit of water permeability on the inner surface of the tubular woven fabric structure of the present invention is preferably 5 mL / min / 120 mmHg (16 kPa) / cm 2 or more from the viewpoint of biocompatibility. more preferably min / 120mmHg / cm 2 or more, even more preferably at 50mL / min / 120mmHg / cm 2 or more.
- the water permeability on the inner surface is a state where both ends of the tubular woven structure are closed on one side, and the other side is filled with sufficiently clean water such as tap water at 25 ° C.
- the amount of water leakage (mL) leaked in 1 minute from the wall surface of the tubular woven structure is measured for 20 minutes so that a water pressure of 120 mmHg (16 kPa) is applied to the inner wall of the woven structure. It means a value divided by the surface area (cm 2 ) of the used multi-tubular fabric structure.
- This water permeability can be used as an index representing the size and amount of the fiber gap of the artificial blood vessel.
- the water permeability can be adjusted by the composition ratio of warp and weft constituting the tubular woven fabric structure whose inner side is in contact with blood, the single yarn diameter, the packing density, the thickness of the antithrombogenic material layer, the hydrophilicity, and the like. .
- ⁇ Antithrombogenicity> In general, when a tubular woven fabric is used as an artificial blood vessel, the living body recognizes it as a foreign substance when transplanted, and a blood clot reaction proceeds on the contact surface of the artificial blood vessel with blood, that is, the inner surface to form a thrombus. Therefore, antithrombotic treatment is preferable.
- a method for improving the antithrombogenicity of a medical material a method of applying heparin or a heparin derivative to the surface of the material has been used.
- heparin or a heparin derivative cannot be directly applied to a medical material made of cloth such as polyester fiber constituting an artificial blood vessel or a medical material made of expanded porous polytetrafluoroethylene (hereinafter, “ePTFE”). Therefore, after modifying the surface of the medical material, heparin or heparin derivative is imparted to the surface of the material by covalent bond (Patent Documents 11 to 13), or heparin or heparin derivative is imparted to the surface of the material by ionic bond. (Patent Documents 14 to 17) have been reported.
- Patent Document 18 As a method of imparting antithrombogenicity to a cloth artificial blood vessel, a method in which heparin or a heparin derivative is included in a gel such as collagen or gelatin absorbed in vivo used to prevent blood leakage and imparted to the surface of the material.
- Patent Document 19 a method of impregnating segmented polyurethane dissolved in an organic solvent and imparting it to the surface of the material.
- the cylindrical woven fabric structure of the present invention can be preferably used as an artificial blood vessel because these treatments prevent thrombus adhesion and can be embedded in a living body for a long period of time. Among them, it is preferable to apply the following antithrombotic material.
- Antithrombogenicity is the property that blood does not clot on the surface that comes into contact with blood, for example, the property that inhibits blood clotting that progresses due to platelet aggregation or activation of blood clotting factors such as thrombin.
- the cell affinity refers to the property that vascular endothelial cells that are present on the inner surface of a living blood vessel and can inhibit the formation of a thrombus are settled and an intima is easily formed.
- the antithrombotic material is a material having antithrombogenicity.
- an antithrombotic material A containing a compound having an anionic anticoagulant activity containing a sulfur atom and a cationic polymer, and a skeleton structure of a hydrophilic polymer
- An antithrombotic material B containing three types of skeleton structures, ie, a skeleton structure of-(aminomethyl) benzenecarboxyimidamide or benzeneamidine and a skeleton structure of methoxybenzenesulfonic acid amide is preferably used.
- an antithrombogenic material layer by bonding an antithrombogenic material to the inside of a tubular woven fabric structure in contact with blood.
- the thickness range of the antithrombogenic material layer is such that if it is too thick, the inner surface of the artificial blood vessel that comes into contact with blood is finely composed of warps and wefts that constitute the tubular woven fabric structure of the present invention whose inside contacts with blood. By destroying the structure, vascular endothelial cells tend not to settle.
- the thickness range of the antithrombotic material layer is too thin, the amount of antithrombogenic material bound is small, and it may be difficult to obtain the optimum antithrombogenicity immediately after transplantation.
- the antithrombogenic material layer formed by bonding the antithrombotic material to the inside of the cylindrical woven fabric structure in contact with blood has an appropriate thickness.
- the thickness range is preferably 1 to 600 nm, more preferably 5 to 500 nm, and even more preferably 15 to 400 nm.
- the thickness of the antithrombogenic material layer can be determined using, for example, a scanning transmission electron microscope (hereinafter referred to as “STEM”) described later. That is, the thickness of the antithrombotic material layer is the number of atoms derived from the antithrombogenic material when the atomic distribution is observed in the vertical direction from the inner layer side to the outer layer side, starting from the inner surface measured by STEM. This is the distance from the start point to the end point of the observed point, and is an average value obtained from the thickness values measured at least at three randomly selected points.
- STEM scanning transmission electron microscope
- the tubular woven fabric structure of the present invention is used for an artificial blood vessel, it is preferable that an antithrombogenic material is also present on the outer layer side of the tubular woven fabric structure that is in contact with blood, that is, in the depth direction.
- the inner surface measured by STEM is, for example, an acrylic resin to be embedded at the time of sample preparation prior to measurement by STEM, and a cylindrical woven fabric that comes into contact with blood, and a cylindrical woven fabric structure that comes into contact with blood on the inside This refers to the part of the atom distribution observed vertically in the direction of the outer layer.
- the starting point is the point where atoms derived from the antithrombotic material were observed in the warp and weft constituting the tubular woven fabric structure in contact with blood on the inside
- the distance from the start point to the end point of the point where atoms derived from the antithrombotic material layer are observed is 15 nm or more, and that the distance from the inner surface of the structure is 15 nm or more.
- the distance from the start point to the end point of the point where the atom derived from the antithrombotic material is observed may exceed 200 nm.
- the fibers constituting the artificial blood vessel are acid or alkali and oxidized. Since an appropriate hydrolysis and oxidation treatment is performed with an agent, deterioration may occur, and mechanical properties such as tensile strength of the artificial blood vessel may be reduced.
- the present invention provides a cylindrical woven structure in which the antithrombotic material is in contact with blood so that the end point of the point where the atoms derived from the antithrombotic material are observed is in the range of 15 to 200 nm in the depth direction. It is preferable to combine with the warp and weft constituting the body.
- the microstructure comprising the warp and the weft constituting the tubular woven fabric structure of the present invention in which the inside contacts with blood
- An antithrombotic material layer having an appropriate thickness is formed by bonding an antithrombotic material to warps and wefts constituting a tubular woven fabric structure in which the inner side is in contact with blood to form an antithrombotic material layer having an appropriate thickness. Endothelial cell colonization and intima formation can be further promoted.
- the STEM includes detectors such as an energy dispersive X-ray spectrometer (hereinafter referred to as “EDX”) and an electron energy loss spectrometer (hereinafter referred to as “EELS”).
- EDX energy dispersive X-ray spectrometer
- EELS electron energy loss spectrometer
- Apparatus Field emission type transmission electron microscope JEM-2100F (manufactured by JEOL)
- EELS detector GIF Tridiem (manufactured by GATAN)
- EDX detector JED-2300T (manufactured by JEOL)
- Image acquisition Digital Micrograph (manufactured by GATAN)
- Sample preparation Ultra-thin section method (suspended on a copper microgrid, embedding resin is acrylic resin) Acceleration voltage: 200 kV Beam diameter: Diameter 0.7nm Energy resolution: about 1.0 eVFFWHM
- the presence of atoms is determined by whether or not the peak intensity derived from each atom is recognized by subtracting the background in the spectrum obtained from the STEM measurement.
- the antithrombotic material A is preferably a compound having an anionic anticoagulant activity containing a sulfur atom.
- a cationic polymer is included.
- the cationic monomer includes a compound selected from the group consisting of alkyleneimine, vinylamine, allylamine, lysine, protamine, and diallyldimethylammonium chloride as a constituent monomer A. More preferably, it contains a polymer.
- the compound containing a sulfur atom having anticoagulant activity is anionic. be able to.
- the anionic anticoagulant compound containing a sulfur atom include heparin or heparin derivatives, dextran sulfate, polyvinyl sulfonic acid and polystyrene sulfonic acid, and heparin or heparin derivatives are more preferable. Heparin or a heparin derivative may be purified or not, and is not particularly limited as long as it can inhibit the blood coagulation reaction.
- Heparin generally used in clinical practice In addition to unfractionated heparin and low molecular weight heparin, anti-thrombin III has high affinity heparin.
- Specific examples of heparin include “heparin sodium” (Organon API).
- the cationic polymer Since the cationic polymer has a cationic property and may develop hemolytic toxicity, it is not preferable to elute it in the blood. Therefore, the cationic polymer is preferably bonded to the warp and weft constituting the tubular woven fabric structure whose inner side is in contact with blood, and more preferably covalently bonded.
- the cationic polymer may be a homopolymer or a copolymer.
- the cationic polymer when it is a copolymer, it may be a random copolymer, a block copolymer, a graft copolymer or an alternating copolymer, but the repeating unit containing a nitrogen atom is continuous.
- a block copolymer is more preferable because the block portion and a compound having an anionic anticoagulant activity containing a sulfur atom interact to form a strong ionic bond.
- the homopolymer means a polymer compound obtained by polymerizing one kind of constituent monomer
- the copolymer means a polymer compound obtained by copolymerization of two or more kinds of monomers.
- the block copolymer is a copolymer having a molecular structure in which at least two kinds of polymers having different repeating units are connected by a covalent bond to form a long chain, and the block is a block copolymer. Each of at least two types of polymers having different repeating units is included.
- the structure of the cationic polymer may be linear or branched.
- a more stable ionic bond can be formed at multiple points with an anionic anticoagulant compound containing a sulfur atom, a branched one is more preferable.
- the cationic polymer has at least one functional group among primary to tertiary amino groups and quaternary ammonium groups.
- the quaternary ammonium groups are Elution rate of a compound having an anionic anticoagulant activity containing a sulfur atom with stronger ionic interaction with the anionic anticoagulant compound containing a sulfur atom than a primary to tertiary amino group Is preferable because it is easy to control.
- the number of carbon atoms of the three alkyl groups constituting the quaternary ammonium group is not particularly limited. However, if the number is too large, the hydrophobicity is high and the steric hindrance increases. Thus, an anionic anticoagulant compound containing a sulfur atom can not be ionically bonded. Further, since too much hemolytic toxicity is likely to occur, the number of carbon atoms per alkyl group bonded to the nitrogen atom constituting the quaternary ammonium group is preferably 1 to 12, and more preferably 2 to 6 Is preferred.
- the three alkyl groups bonded to the nitrogen atom constituting the quaternary ammonium group may all have the same carbon number or may be different.
- polyalkyleneimine as the cationic polymer because of the large amount of adsorption based on the ionic interaction with the anionic anticoagulant compound containing a sulfur atom.
- the polyalkyleneimine include polyethyleneimine (hereinafter “PEI”), polypropyleneimine and polybutyleneimine, and further alkoxylated polyalkyleneimine. Among them, PEI is more preferable.
- PEI examples include “LUPASOL” (registered trademark) (manufactured by BASF) and “EPOMIN” (registered trademark) (manufactured by Nippon Shokubai Co., Ltd.). It may be a copolymer with another monomer or a modified product.
- the modified body is the same as the repeating unit of the monomer A constituting the cationic polymer, but for example, a part of which has undergone radical decomposition, recombination, etc. due to radiation irradiation described later. Point to.
- the constituent monomer for forming the copolymer used in addition to alkyleneimine, vinylamine, allylamine, lysine, protamine and diallyldimethylammonium chloride is not particularly limited, but for example, ethylene
- the constituent monomer B include glycol, propylene glycol, vinyl pyrrolidone, vinyl alcohol, vinyl caprolactam, vinyl acetate, styrene, methyl methacrylate, hydroxyethyl methacrylate, and siloxane.
- the cationic polymer tends to weaken the ionic bond with the anionic anticoagulant compound containing a sulfur atom, so the constituent monomer with respect to the total weight of the cationic polymer.
- the weight of B is preferably 10% by weight or less.
- the weight average molecular weight of the cationic polymer if the weight average molecular weight of the cationic polymer is too small, the molecular weight tends to be smaller than that of an anionic anticoagulant compound containing a sulfur atom, so that a stable ionic bond is not formed. It is difficult to obtain antithrombogenicity.
- the weight average molecular weight of the cationic polymer if the weight average molecular weight of the cationic polymer is too large, an anionic anticoagulant compound containing a sulfur atom is encapsulated by the cationic polymer, and the antithrombotic material is easily buried.
- the weight average molecular weight of the cationic polymer is preferably from 600 to 2,000,000, more preferably from 1,000 to 1500,000, and even more preferably from 10,000 to 1,000,000.
- the weight average molecular weight of the cationic polymer can be measured by, for example, a gel permeation chromatography method or a light scattering method.
- an anionic property containing a sulfur atom while maintaining a fine structure comprising a warp and a weft containing a microfiber having a single yarn fineness of less than 1.0 dtex, constituting a tubular woven fabric structure whose inner side is in contact with blood
- the present inventors have intensively studied.
- the abundance ratio of atoms is represented by “number of atoms%”.
- the number of atoms% indicates the abundance ratio of specific atoms in terms of the number of atoms when the abundance of all atoms is 100.
- the abundance ratio of sulfur atoms to the abundance of all atoms on the inner surface measured by XPS is preferably 3.0 to 6.0 atomic%, and 3.2 to 5.5 atomic%. More preferred is 3.5 to 5.0 atomic%.
- the ratio of sulfur atoms to the total amount of atoms is less than 3.0% by number, the amount of anionic anticoagulant compound containing sulfur atoms decreases, so it is excellent immediately after transplantation of an artificial blood vessel. Antithrombogenicity is difficult to obtain.
- the abundance ratio of sulfur atoms with respect to the abundance of all atoms is 6.0 atom number% or less, the binding amount of an anionic anticoagulant compound containing sulfur atoms will be an appropriate amount. Endothelial cell colonization is promoted.
- the abundance ratio of sulfur atoms to the abundance of all atoms on the inner surface can be determined by XPS.
- Apparatus ESCALAB 220iXL (manufactured by VG Scientific)
- the inner surface measured by X-ray photoelectron spectroscopy refers to the surface of the artificial blood vessel inner layer that is opened by opening the artificial blood vessel. Further, from the measurement surface detected when the X electron escape angle under the XPS measurement conditions, that is, when the inclination of the detector with respect to the inner surface of the artificial blood vessel in which the antithrombotic material and the tubular fabric are combined is 90 °, is measured. The depth is up to 10 nm.
- the fiber of the tubular woven fabric structure may contain sulfur atoms not derived from the antithrombotic material or may not contain sulfur atoms.
- the atomic energy of the inner surface measured by XPS can be obtained from the binding energy value of the bound electrons in the substance.
- Information on the valence and bonding state can be obtained from the energy shift of the peak of the energy value. Furthermore, quantitative determination using the area ratio of each peak, that is, the existence ratio of each atom, valence, and bonding state can be calculated.
- the S2p peak indicating the presence of a sulfur atom is observed at a binding energy value near 161 eV to 170 eV, and in the present invention, the area ratio of the S2p peak to the total peak is 3.0 to 6.0 atomic%. It was found that it is preferable.
- the abundance ratio of sulfur atoms to the abundance of all atoms is calculated by rounding off the second decimal place.
- the ratio of nitrogen atoms to the total amount of atoms on the inner surface measured by XPS is preferably 6.0 to 12.0 atomic percent, more preferably 7.0 to 12.0 atomic percent, More preferred is 0.5 to 11.0 atomic percent, and even more preferred is 8.0 to 10.0 atomic percent.
- the abundance ratio of nitrogen atoms to the abundance of all atoms is less than 6.0%, the amount of the cationic polymer that binds to the tubular fabric structure that contacts the blood on the inside decreases, so although the microstructure comprising the warp and the weft comprising the microfiber having a single yarn fineness of less than 1 dtex is retained, the anionic anti-ionic agent containing a sulfur atom ionically bonded to the cationic polymer is retained. Since the binding amount of the compound having the coagulation activity is reduced, it is difficult to obtain the optimum antithrombotic properties immediately after the transplantation of the artificial blood vessel.
- the abundance ratio of nitrogen atoms with respect to the abundance of all atoms exceeds 12.0 atomic%, the amount of the cationic polymer that binds to the tubular woven fabric structure in contact with blood on the inside increases.
- anionic anticoagulant compound containing sulfur atoms that ionically bond to the water-soluble polymer, but as the anionic anticoagulant compound containing sulfur atoms elutes, the amount of cationic compounds increases. It was found that the polymer is exposed and therefore exhibits hemolytic toxicity.
- the abundance ratio of nitrogen atoms with respect to the abundance of all atoms is 12.0 atomic% or less, the binding amount of an anionic anticoagulant compound containing a sulfur atom becomes an appropriate amount. Endothelial cell colonization is promoted.
- the abundance ratio of nitrogen atoms to the total abundance of atoms is preferably 6.0 to 12.0 atomic%, and 6.0 to 9.5 atomic%. Is more preferable, and 8.0 to 9.5 atomic% is even more preferable.
- the N1s peak indicating the presence of a nitrogen atom is observed in the vicinity of a binding energy value of 396 eV to 403 eV.
- the area ratio of the N1s peak to the entire peak is 7.0 to 12.0 atomic%. It was found that it is preferable.
- the N1s peak is mainly composed of an n1 component (near 399 eV) attributed to a carbon-nitrogen (hereinafter “CN”) bond, an ammonium salt, CN (a structure different from n1), or a nitrogen oxide.
- the peak can be divided into n2 components (near 401 to 402 eV) belonging to (hereinafter “NO”).
- the existence ratio of each divided peak component is calculated by the following equation 2.
- the abundance ratio of nitrogen atoms to the abundance of all atoms and the abundance ratio of each divided peak component are calculated by rounding off the first decimal place.
- the n2 component attributed to NO obtained by the division of the N1s peak indicates the presence of a quaternary ammonium group, and the abundance ratio of the n2 component to the total components of the N1s peak, that is, the divided percent (n2 ) Is preferably 20 to 70 atomic%, more preferably 25 to 65 atomic%, and further preferably 30 to 60 atomic%.
- the divided percent (n2) is less than 20 atomic%, the amount of quaternary ammonium groups is small, so that the ionic interaction with an anionic anticoagulant compound containing a sulfur atom is weak, and the dissolution rate is low.
- the divided percent (n2) exceeds 70 atomic%, the ionic interaction with the anionic anticoagulant compound containing a sulfur atom tends to be strong, and the freedom due to the formation of an ionic complex is increased. Due to the decrease in the degree, not only the anticoagulant activity cannot be expressed for a long time, but also the elution rate tends to be slow. Further, since the abundance ratio of the n2 component, that is, the division ratio (n2) is calculated by the equation 2, it is preferably 1.4 to 8.4 atomic% for the above reason, and is preferably 1.8 to 7.2 atoms. Several percent is more preferred, and 2.4 to 6.0 atomic percent is even more preferred.
- the C1s peak indicating the presence of carbon atoms is seen in the vicinity of a binding energy value of 282 to 292 eV, and the C1s peak is mainly a carbon-hydrogen (hereinafter “CHx”) bond that suggests the presence of saturated hydrocarbons or the like.
- CHx carbon-hydrogen
- the c3 component attributed to the C ⁇ O bond obtained by splitting the C1s peak indicates the presence of an amide group in the present invention.
- the abundance ratio of the c3 component with respect to all components of the C1s peak ie, In the present invention, it has been found that the abundance ratio of the amide group is preferably 2.0 atomic% or more, more preferably 3.0 atomic% or more.
- the abundance ratio of the amide group is less than 2.0 atomic%, since the covalent bond due to the amide bond is reduced between the cationic polymer and the tubular woven fabric structure in which the inside is in contact with blood, As the amount of binding decreases, the ion binding state between the cationic polymer and the anionic anticoagulant compound containing a sulfur atom is deteriorated, so that it is difficult to obtain optimum antithrombogenicity.
- the antithrombotic material B of the present invention has three types of skeletons: a skeleton structure of a hydrophilic polymer, a skeleton structure of 4- (aminomethyl) benzenecarboxyimidamide or benzeneamidine, and a skeleton structure of methoxybenzenesulfonic acid amide. It preferably includes a structure.
- the hydrophilic polymer include monomers selected from the group consisting of ethylene glycol, propylene glycol, vinyl pyrrolidone, vinyl alcohol, vinyl caprolactam, vinyl acetate, styrene, methyl methacrylate, hydroxyethyl methacrylate, and siloxane. More preferably, B is included.
- skeleton structures may be included in separate compounds, or may be compounds in which at least two skeleton structures are bonded by a covalent bond or an ionic bond.
- antithrombogenic material B a compound containing all the structures of a hydrophilic polymer skeleton structure, a 4- (aminomethyl) benzenecarboxyimidamide or benzeneamidine skeleton structure, and a methoxybenzenesulfonic acid amide skeleton structure is used. It is more preferable for the artificial blood vessel of the present invention to achieve both antithrombogenicity and cell affinity.
- any one of the three kinds of skeleton structures has a functional group selected from the group consisting of, for example, a hydroxyl group, a thiol group, an amino group, a carboxyl group, an aldehyde group, an isocyanate group, and a thioisocyanate group.
- a functional group selected from the group consisting of, for example, a hydroxyl group, a thiol group, an amino group, a carboxyl group, an aldehyde group, an isocyanate group, and a thioisocyanate group.
- it has an amino group or a carboxyl group, more preferably has an amino group.
- the functional group is preferably contained in the skeleton structure of the hydrophilic polymer, and more preferably present at the end of the skeleton structure of the hydrophilic polymer.
- Warp and weft constituting a tubular woven fabric structure whose inside is in contact with blood using a functional group selected from the group consisting of a hydroxyl group, a thiol group, an amino group, a carboxyl group, an aldehyde group, an isocyanate group and a thioisocyanate group
- a functional group selected from the group consisting of a hydroxyl group, a thiol group, an amino group, a carboxyl group, an aldehyde group, an isocyanate group and a thioisocyanate group
- three types of skeleton structures can form covalent bonds such as disulfide bonds, amide bonds, ester bonds, urethane bonds, and bonds by condensation reactions.
- the antithrombotic material is provided with a reactive functional group, whereby a method such as radiation irradiation is performed. It can be covalently bonded without use.
- a covalent bond is formed by irradiation or the like, the skeleton structure of 4- (aminomethyl) benzenecarboxyimidamide or benzeneamidine and the skeleton structure of methoxybenzenesulfonic acid amide absorb high energy by radiation.
- radicals with very high reactivity are generated, and the skeletal structure changes due to the reaction between the unspecified sites of the compound and the radicals, and the antithrombin activation performance mainly decreases.
- the inventors of the present application have made extensive studies. As a result, it was found that the skeleton structure of the hydrophilic polymer is important.
- the skeleton structure of the hydrophilic polymer refers to a skeleton structure of a polymer having a hydrophilic functional group and solubility in water, and the hydrophilic polymer is different from other monomers within a range not impeding the effects of the present invention.
- the copolymer may be a modified product.
- the skeleton structure of the hydrophilic polymer may be a homopolymer or a copolymer as long as the constituent monomer B is used.
- the hydrophilic polymer when it is a copolymer, it may be any of a random copolymer, a block copolymer, a graft copolymer, or an alternating copolymer.
- the skeleton structure of the hydrophilic polymer may be linear or branched.
- the inventors of the present application have earnestly studied. As a result of investigation, it was found that the skeleton structure of 4- (aminomethyl) benzenecarboxyimidamide or benzeneamidine and the skeleton structure of methoxybenzenesulfonic acid amide are important.
- the skeleton structure of 4- (aminomethyl) benzenecarboximidamide is a skeleton structure represented by the following general formula (V)
- the skeleton structure of benzeneamidine is a skeleton structure represented by the following general formula (VI).
- the skeleton structure of the methoxybenzenesulfonic acid amide is a skeleton structure represented by the following general formula (VII). [Wherein, R1 is a moiety linked to another skeleton structure. ] [Wherein R2 is a moiety linked to other skeleton structure. ] [Wherein, R3 and R4 are moieties linked to other skeleton structures. ]
- a compound containing all three types of structures such as a skeleton structure of a hydrophilic polymer, a skeleton structure of 4- (aminomethyl) benzenecarboxyimidamide or benzeneamidine and a skeleton structure of methoxybenzenesulfonic acid amide
- a compound represented by the formulas (I) to (IV) it is preferable that X is an amino group or a carboxyl group, and it is still more preferable that X is an amino group.
- n and o represent an integer of 0 to 4
- n represents an integer of 3 to 1000
- n ′ represents an integer of 3 to 1000
- X represents a functional group selected from the group consisting of a hydroxyl group, a thiol group, an amino group, a carboxyl group, an aldehyde group, an isocyanate group, and a thioisocyanate group.
- X in the above formula may be contained in any of three types of skeletal structures, but the inside has a hydrophilic property that has antiplatelet adhesion performance on the side close to the tubular woven fabric structure in contact with blood.
- a skeletal structure of a functional polymer there is a skeletal structure of 4- (aminomethyl) benzenecarboxyimidamide or benzeneamidine and a methoxybenzenesulfonic acid amide having antithrombin activation performance on the side in contact with blood
- the latter skeletal structure has a higher ability to capture thrombin and can exhibit high antithrombogenicity.
- the reactive functional group (X in the above formula) to be covalently bonded to the warp and the weft constituting the tubular woven fabric structure that is in contact with blood is contained in the skeleton structure of the hydrophilic polymer. More preferably, it exists at the end of the skeleton structure of the hydrophilic polymer.
- the bond refers to a chemical bond such as a covalent bond, a hydrogen bond, an ionic bond, and a coordination bond.
- a covalent bond refers to a chemical bond formed by sharing electrons between atoms.
- the kind of covalent bond is not limited, For example, an amine bond, an azide bond, an amide bond, an imine bond etc. are mentioned. Among these, an amide bond is more preferable from the viewpoints of easy formation of a covalent bond and stability after bonding.
- the confirmation of the covalent bond can be determined from the fact that even if the artificial blood vessel is washed with a solvent that dissolves the antithrombotic material, it does not elute.
- the antithrombotic material B contains a betaine compound, and the warp and weft constituting the tubular woven fabric structure in which the inside contacts with blood Or it discovered that it was more preferable that it is covalently bonded with the said antithrombogenic material B.
- a betaine compound has a positive charge and a negative charge at positions that are not adjacent to each other in the same molecule, and a positively charged atom is not bonded with a dissociable hydrogen atom, and the molecule as a whole has a charge.
- it is not particularly limited as long as it is a compound partially containing a betaine compound, but carboxybetaine, sulfobetaine and phosphobetaine are preferred, and in particular, More preferred is carboxybetaine or sulfobetaine represented by the general formula (VIII) or (IX).
- X in the formula of general formula (VIII) or (IX) is preferably an amino group or a carboxyl group, and X is more preferably an amino group.
- n any one of 1 to 4
- m represents an integer of 2 to 4
- n ′ represents an integer of 2 to 4
- m ′ represents 2 to 4
- X represents an integer
- X represents a functional group selected from the group consisting of a hydroxyl group, a thiol group, an amino group, a carboxyl group, an aldehyde group, an isocyanate group, and a thioisocyanate group.
- the skeleton structure of the hydrophilic polymer on the innermost surface measured by time-of-flight secondary ion mass spectrometry (hereinafter referred to as “TOF-SIMS”)
- TOF-SIMS time-of-flight secondary ion mass spectrometry
- TOF-SIMS is measured by opening an artificial blood vessel and measuring the exposed artificial blood vessel inner layer.
- innermost surface measured by TOF-SIMS refers to a depth of 1 to 3 nm from the measurement surface under the TOF-SIMS measurement conditions.
- a pulsed primary ion is irradiated on the innermost surface in an ultra-high vacuum, and the secondary ion emitted from the innermost surface measured by TOF-SIMS obtains a constant kinetic energy to obtain a time-of-flight mass. Guided to the analyzer. Since a mass spectrum is obtained according to the mass of the secondary ion, information on the abundance can be obtained from the identification of the organic and inorganic substances present on the innermost surface measured by TOF-SIMS and the peak intensity.
- the skeleton structure of ethylene glycol or propylene glycol on the innermost surface measured by TOF-SIMS is a 45 C 2 H 5 O + peak of a positive secondary ion observed by TOF-SIMS, 59 C 3 H 7. It is confirmed by at least one peak selected from the group consisting of O + peak, 73 C 3 H 5 O 2 + peak, and 87 C 4 H 7 O 2 + peak.
- the skeleton structure of 4- (aminomethyl) benzenecarboximidamide on the innermost surface measured by TOF-SIMS is a 106 C 7 H 8 N + peak of a positive secondary ion observed by TOF-SIMS, 117 C At least selected from the group consisting of : 7 H 5 N 2 + peak, 134 C 8 H 10 N 2 + peak, 148 C 8 H 10 N 3 + peak, 119 C 7 H 7 N 2- peak of negative secondary ion confirmed a kind of peak skeletal structure of benzene amidine is 119 negative secondary ions observed by TOF-SIMS C 7 H 7 N 2 - confirmed by a peak of a skeleton methoxy benzenesulfonic acid amide, positive Secondary ion 117 C 7 H 7 SO 3 + peak, negative secondary ion 64 SO 2 - peak, 171 C 7 H 7 SO 3 - peak, 186 C 7 H 8 SNO 3 - peak, 212 C 9 H 10 SNO 3 - is
- the presence of betaine compound in the innermost surface measured by TOF-SIMS is, 94 CH 2 SO negative secondary ions observed by TOF-SIMS 3 - peak, 150 C 4 H 8 NSO 3 - peak, 166 C 5 H 12 NSO 3 - is confirmed in at least one peak selected from the group consisting of peaks.
- the presence of PEI on the innermost surface indicates that 18 NH 4 + peaks of positive secondary ions, 28 CH 2 N + peaks, 43 CH observed by TOF-SIMS. This is confirmed by at least one peak selected from the group consisting of 3 N 2 + peak, 70 C 4 H 8 N + peak, negative secondary ion 26 CN ⁇ peak, and 42 CNO ⁇ peak.
- PAA polyacrylic acid
- the presence of polyethylene terephthalate is the positive secondary ion 76 C 6 H 4 + observed by TOF-SIMS.
- Peak, 104 C 7 H 4 NO + peak, 105 C 7 H 5 O + peak, 149 C 8 H 5 O 3 + peak, negative secondary ion 76 C 6 N 4 - peak, 120 C 7 H 4 O 2 - peak, 121 C 7 H 5 O 2 - peak, 147 C 9 H 7 O 2 - peak, 165 C 8 H 5 O 4 - is confirmed in at least one peak selected from the group consisting of peaks.
- the abundance ratio of the skeleton structure of 4- (aminomethyl) benzenecarboxyimidamide or benzeneamidine and the skeleton structure of methoxybenzenesulfonic acid amide to PAA on the innermost surface is There are preferred ranges.
- Negative second ion 71 C 3 H 3 O 2 for the presence of PAA is observed by TOF-SIMS - peak, 4- presence of (aminomethyl) benzene carboximidamide or benzene amidine skeleton structure observed by TOF-SIMS is taken as the peak, the peak ratio, 119 C 7 H 7 N 2 - - is 119 negative secondary ions C 7 H 7 N 2 peaks / 71 C 3 H 3 O 2 - peak, 0.05 The above is preferable.
- the 2 - peak is preferably 0.5 or more.
- the present inventors when the antithrombotic material B is used for an artificial blood vessel, the present inventors have made extensive studies in order to achieve both antithrombogenicity and cell affinity while suppressing the elution of the compound. It was found that there is a preferable value for the abundance ratio of the split peak component of the c3 component attributed to the C ⁇ O bond, which suggests the presence of a carbonyl group with respect to the C1s peak indicating the presence of carbon atoms on the inner surface, as measured in (1).
- the abundance ratio of the c3 component split peak component to the total component of the C1s peak on the inner surface measured by XPS is preferably 1.0 atomic percent or more, more preferably 2.0 atomic percent or more, and 3.0 It has been found that more than a few percent is even more preferable.
- the antithrombosis that binds to the tubular woven fabric structure that contacts the blood on the inside Since there is a sufficient amount of binding of the conductive material B, as shown in Patent Documents 15 and 16, the antithrombogenic property can be expressed higher and longer than when the antithrombotic material is covalently bonded by irradiation. it can.
- Warp and weft constituting a tubular woven fabric structure in which the inside is in contact with blood when the abundance ratio of the c3 component split peak component to the total component of the C1s peak on the inner surface measured by XPS is less than 1.0 atomic%
- the anti-thrombogenic material B is less covalently bonded by an amide bond derived from a carbonyl group, and the amount of the anti-thrombogenic material B is reduced, so that the desired antithrombogenicity is hardly obtained.
- the abundance ratio of nitrogen atoms to the total amount of atoms is 1.0 to 12.0. It has been found that the atomic percentage is preferably 2.0 to 11.0 atomic%, more preferably 3.0 to 10.0 atomic%.
- the number average molecular weight of the skeleton structure of the hydrophilic polymer in the antithrombotic material B is preferably 1500 to 20000, and more preferably 2000 to 10,000.
- the antithrombotic material B containing three kinds of skeleton structures, ie, a skeleton structure of a polymer, a skeleton structure of 4- (aminomethyl) benzenecarboxyimidamide or benzeneamidine, and a skeleton structure of methoxybenzenesulfonic acid amide, A functional polymer may be included.
- the antithrombotic material of the present invention is additionally selected from the group consisting of acrylic acid, methacrylic acid, ⁇ -glutamic acid, ⁇ -glutamic acid and aspartic acid.
- an anionic compound selected from the group consisting of dicarboxylic acids such as diacids and citric acid.
- the anionic polymer is not particularly limited, but the higher the weight ratio of the anionic functional group, the warp and the weft constituting the tubular woven structure whose inner side is in contact with blood, or other antithrombogenicity Since the amount of binding with the material increases, it is preferable to use PAA, polymethacrylic acid, poly ⁇ -glutamic acid, poly ⁇ -glutamic acid, and polyaspartic acid, and more preferably PAA.
- PAA examples include “polyacrylic acid” (manufactured by Wako Pure Chemical Industries, Ltd.) and the like, but may be a copolymer with other monomers as long as the effects of the present invention are not hindered. It may be a body.
- the anionic polymer is not particularly limited, but may form a copolymer with a monomer other than the anionic monomer, such as ethylene glycol, propylene glycol, vinyl pyrrolidone, vinyl alcohol, vinyl caprolactam. And constituent monomers B such as vinyl acetate, styrene, methyl methacrylate, hydroxyethyl methacrylate, and siloxane. If the amount of the constituent monomer B other than the anionic monomer that forms a copolymer with the anionic polymer is too large, the amount of the binding to the tubular woven fabric structure or other antithrombotic material whose inside contacts with blood decreases. Therefore, it is preferably 10% by weight or less.
- the anionic polymer is eluted in the blood from the viewpoint of safety and the like. Therefore, the anionic polymer is preferably bonded to the warp and weft constituting the tubular woven fabric structure whose inner side is in contact with blood, and more preferably covalently bonded.
- the cationic polymer may be a homopolymer or a copolymer.
- the anionic polymer when it is a copolymer, it may be a random copolymer, a block copolymer, a graft copolymer, or an alternating copolymer.
- the constituent monomer for forming the copolymer used in addition to acrylic acid, methacrylic acid, ⁇ -glutamic acid, ⁇ -glutamic acid and aspartic acid is not particularly limited.
- the constituent monomer B include ethylene glycol, propylene glycol, vinyl pyrrolidone, vinyl alcohol, vinyl caprolactam, vinyl acetate, styrene, methyl methacrylate, hydroxyethyl methacrylate, and siloxane.
- the weight of the constituent monomer B with respect to the total weight of the conductive polymer is preferably 10% by weight or less.
- the anionic compound is not particularly limited, but the higher the weight ratio of the anionic functional group, the greater the amount of binding with the tubular woven fabric structure or other antithrombotic material that is in contact with blood on the inside. Therefore, it is preferable to use oxalic acid, malonic acid, succinic acid, fumaric acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, malic acid, tartaric acid and citric acid, and succinic acid is more preferred. preferable.
- the weight average molecular weight of the anionic polymer is preferably from 600 to 2,000,000, more preferably from 10,000 to 1,000,000.
- the tubular woven fabric structure of the present invention can be preferably used as a base material for an artificial blood vessel, and the artificial blood vessel obtained therefrom has a small amount of blood leakage and can achieve both antithrombogenicity and cell affinity. It is a feature. Therefore, it can be applied to general artificial blood vessels, but it is particularly suitable for artificial blood vessels having a small inner diameter, which do not have good long-term results and cannot be used for clinical use at present. That is, the inner diameter of the artificial blood vessel is preferably 1 to 10 mm, and more preferably 1 to 6 mm.
- the cover factor (CF) is a value calculated from the total fineness and base fabric density of the yarn used for the warp or weft.
- the total warp fineness is Dw (dtex)
- the total weft fineness is Df (dtex)
- Nw line / 2.54 cm
- Nf line / 2.54 cm
- Cover factor CFa Dw 1/2 ⁇ Nw in the longitudinal direction
- Cover factor in the weft direction CFb Df 1/2 ⁇ Nf
- the base fabric density was determined based on a photograph in which the produced tubular woven structure was cut in the length direction of the cylinder and the inner wall surface was enlarged 50 times with a Kiens microscope VHX-2000. , Measured.
- the kink radius was measured by measuring the kink radius.
- the tubular woven fabric structure was looped, and the radius at which bending was apparently observed in appearance was measured using a cylindrical jig with a known radius. In order to evaluate the characteristics of the woven tubular body itself, the internal pressure was not maintained.
- Width of tubular woven fabric structure A metal ruler is pressed perpendicularly to the length direction of the tubular woven fabric structure, the cross section of the tubular woven fabric is crushed, and the fabric width is measured. The measurement was performed once for each of three randomly selected locations of the tubular woven structure, and the average value was obtained.
- a tube containing 25 ° C. bovine blood is placed on the other side of the both ends of the leaky tubular woven fabric structure, with one side closed, and the tube is placed inside the tubular woven fabric structure.
- Bovine blood was passed from the inside toward the outside for 20 minutes until the whole artificial blood vessel was sufficiently impregnated under the condition that the pressure was 120 mmHg (16 kPa), and then the flow rate (mL) was collected for 5 to 20 minutes. .
- the value obtained by dividing the fluid flow rate (mL) by the inner surface area (cm 2 ) and unit time (min) of the artificial blood vessel was defined as the amount of blood leakage at 120 mmHg (16 kPa). The measurement was performed 3 times and the average value was obtained.
- the thickness of the antithrombotic material layer was evaluated by STEM. After preparing a cross-section sample of an artificial blood vessel by the ultrathin section method, the thickness at which sulfur atoms derived from the antithrombotic material are observed using the STEM-EDX method under the following conditions, the antithrombogenicity using the STEM-EELS method The thickness at which nitrogen atoms derived from the material were observed was analyzed.
- the average thickness here refers to an average value of at least three points extracted at random.
- a tubular fabric was driven by a shuttle loom with a warp complete double plain weave structure and weaved at a weft number of 202 / cm to form a tube having an inner diameter of 3 mm.
- This cylindrical fabric is scoured at 80 ° C., then treated with boiling water for 5 minutes, dried at 120 ° C. dry heat, a rod-shaped jig is inserted into the tube, and heat-set at 170 ° C. in a cylindrical shape, A tubular woven structure was obtained.
- the tubular fabric structure was evaluated for kink resistance, tensile properties, cover factor, water permeability, and blood leakage. The results are shown in Table 1, Table 2, and Table 3.
- the tensile properties were flexible stretch properties, excellent shape retention, and kink resistance, water permeability and blood leakage resistance required for artificial blood vessels.
- Example 2 As the weft of the inner layer of the tubular woven fabric structure, a PET microfiber having a single yarn fineness of about 0.08 dtex, a total weaving degree of 52.8 dtex, and a filament number of 630 is prepared, and this is used during weaving. A tubular woven fabric similar to that described in Example 1 was prepared except that the density was 186 / cm.
- the obtained tubular woven fabric was evaluated for kink resistance, tensile properties, cover factor, water permeability, and blood leakage of the tubular woven fabric.
- the results are shown in Table 1, Table 2, and Table 3.
- the tensile properties were flexible stretch properties, excellent shape retention, and kink resistance, water permeability and blood leakage resistance required for artificial blood vessels.
- Example 3 The number of wefts driven during weaving in Example 1 is 202 / cm, but the same cylinder as described in Example 1 except that the number of wefts driven during weaving in Example 3 was 158 / cm. A woven fabric was prepared.
- the obtained tubular woven fabric was evaluated for kink resistance, tensile properties, cover factor, water permeability, and blood leakage of the tubular woven fabric.
- the results are shown in Table 1, Table 2, and Table 3.
- the elongation at the time of 3.3N load per 1m width of the tubular woven fabric structure is higher than those of Examples 1 and 2, and has a flexible stretch property, and has the kink resistance, water permeability and blood leakage resistance required for artificial blood vessels.
- Example 1 and 2 The elongation at the time of 3.3N load per 1m width of the tubular woven fabric structure is higher than those of Examples 1 and 2, and has a flexible stretch property, and has the kink resistance, water permeability and blood leakage resistance required for artificial blood vessels.
- Example 4 The number of wefts driven during weaving in Example 2 is 186 / cm, but the same cylinder as described in Example 2 except that the number of wefts driven during weaving in Example 4 is 125 / cm. A woven fabric was prepared.
- the obtained tubular woven fabric was evaluated for kink resistance, tensile properties, cover factor, water permeability, and blood leakage of the tubular woven fabric.
- the results are shown in Table 1, Table 2, and Table 3.
- the tensile properties were as flexible as those in Example 3 and had the kink resistance, water permeability, and blood leakage resistance required for artificial blood vessels.
- Example 5 The tubular woven fabric structure of Example 1 was immersed in an aqueous solution of 5.0% by weight potassium permanganate (manufactured by Wako Pure Chemical Industries, Ltd.), 0.6 mol / L sulfuric acid (manufactured by Wako Pure Chemical Industries, Ltd.), The tubular fabric structure was hydrolyzed and oxidized by reacting at 60 ° C. for 3 hours.
- potassium permanganate manufactured by Wako Pure Chemical Industries, Ltd.
- 0.6 mol / L sulfuric acid manufactured by Wako Pure Chemical Industries, Ltd.
- the obtained artificial blood vessel (Sample 1) was evaluated for antithrombogenicity and cell affinity by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, complete occlusion was not observed 28 days after transplantation, and “ ⁇ ”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was 5.0 mm or more, and “ ⁇ ”. It was.
- Example 6 The same operation as in Example 5 was performed using the tubular woven fabric structure of Example 1, hydrolyzed and oxidized, and PEI was covalently bonded by a condensation reaction, and then 0.5 wt% DMT-MM, 40 It was immersed in dimethylacetamide of weight% succinic anhydride (manufactured by Wako Pure Chemical Industries, Ltd.) and reacted at 50 ° C. for 17 hours.
- Example 2 An artificial blood vessel (sample 2) having an antithrombotic material layer formed with heparin sodium was obtained.
- the obtained artificial blood vessel (Sample 2) was evaluated for antithrombogenicity and cell affinity by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, complete occlusion was not seen 28 days after transplantation, and “ ⁇ ”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was 2.0 mm or more and less than 5.0 mm, It was “ ⁇ ”.
- Example 7 The cylindrical woven structure of Example 1 was subjected to the same operation as in Example 5, hydrolyzed and oxidized, and PEI was covalently bonded by a condensation reaction, and then 0.5 wt% DMT-MM, 0 It was immersed in an aqueous solution of 5 wt% PAA (polyacrylic acid, weight average molecular weight 1 million; manufactured by Wako Pure Chemical Industries, Ltd.) and reacted at 30 ° C. for 2 hours.
- PAA polyacrylic acid, weight average molecular weight 1 million
- Example 3 An artificial blood vessel (sample 3) having an antithrombotic material layer formed with heparin sodium was obtained.
- the obtained artificial blood vessel (Sample 3) was evaluated for antithrombogenicity and cell affinity by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, complete occlusion was not seen 28 days after transplantation, and “ ⁇ ”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was 2.0 mm or more and less than 5.0 mm, It was “ ⁇ ”.
- Example 8 The same procedure as in Example 7 was performed to obtain an artificial blood vessel in which PEI was changed to polyallylamine hydrochloride (hereinafter referred to as “PAH”) (weight average molecular weight 900,000; manufactured by Sigma-Aldrich), and PEI was poly-L -An artificial blood vessel changed to lysine hydrobromide (hereinafter referred to as PLys) (weight average molecular weight 30,000 to 70,000; manufactured by Sigma-Aldrich) was obtained.
- PAH polyallylamine hydrochloride
- PLys poly-L -An artificial blood vessel changed to lysine hydrobromide
- sample 4 the artificial blood vessel in which the antithrombotic material layer was formed by changing to PAH was used as sample 4, and the artificial blood vessel in which the antithrombogenic material layer was formed by changing to PLys was used as sample 5.
- the obtained artificial blood vessels (samples 4 and 5) were evaluated for antithrombogenicity and cytophilicity by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, complete occlusion was not seen 28 days after transplantation, and “ ⁇ ”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was 2.0 mm or more and less than 5.0 mm, It was “ ⁇ ”.
- Example 9 The same operation as in Example 5 was performed, and heparin sodium was changed to dextran sulfate sodium (manufactured by Wako Pure Chemical Industries, Ltd.) to obtain an artificial blood vessel (sample 6) on which an antithrombotic material layer was formed.
- the obtained artificial blood vessel (sample 6) was evaluated for antithrombogenicity and cell affinity by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, complete occlusion was not seen 28 days after transplantation, and “ ⁇ ”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was 2.0 mm or more and less than 5.0 mm, It was “ ⁇ ”.
- Example 10 About the cylindrical textile structure of Example 1, after performing the same operation as Example 5, and hydrolyzing and oxidizing, 1.0 weight% of compound A (following general formula (X)), with respect to compound A It is immersed in an aqueous solution in which 2 molar equivalents of sodium hydroxide and 3 molar equivalents of DMT-MM are dissolved, reacted at 30 ° C. for 2 hours, and compound A is covalently bonded to the cylindrical fabric 1 by a condensation reaction. An artificial blood vessel (sample 7) on which a thrombotic material layer was formed was obtained.
- the obtained artificial blood vessel (sample 7) was evaluated for antithrombogenicity and cell affinity by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, complete occlusion was not seen 28 days after transplantation, and “ ⁇ ”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was 2.0 mm or more and less than 5.0 mm, It was “ ⁇ ”.
- Example 11 The same operation as in Example 10 was performed, and compound A was converted to compound B (the following general formula (XI)), compound C (the following general formula (XII)), and compound D (the following general formula (XIII)). Modified artificial blood vessels were obtained respectively.
- the artificial blood vessel in which the anti-thrombogenic material layer was formed by changing to compound B was changed to sample 8
- the artificial blood vessel in which the anti-thrombogenic material layer was changed to compound C was changed to sample 9
- the anti-thrombogenic material layer was changed to compound D.
- a sample 10 was an artificial blood vessel in which a thrombotic material layer was formed.
- the obtained artificial blood vessels (samples 8 to 10) were evaluated for antithrombogenicity and cell affinity by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, complete occlusion was not seen 28 days after transplantation, and “ ⁇ ”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was 2.0 mm or more and less than 5.0 mm, It was “ ⁇ ”.
- Example 12 The tubular woven structure of Example 1 was subjected to the same operation as in Example 5, hydrolyzed and oxidized, and PEI was covalently bonded by a condensation reaction, and then 0.5 wt% DMT-MM, 0.5 It was immersed in an aqueous solution of weight% PAA (weight average molecular weight 1 million; manufactured by Wako Pure Chemical Industries, Ltd.) and reacted at 30 ° C. for 2 hours.
- weight% PAA weight average molecular weight 1 million
- Example 11 An artificial blood vessel (sample 11) in which A was covalently bonded by a condensation reaction to form an antithrombotic material layer was obtained.
- the obtained artificial blood vessel (sample 11) was subjected to antithrombogenicity evaluation and cell affinity evaluation by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, complete occlusion was not seen 28 days after transplantation, and “ ⁇ ”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was 2.0 mm or more and less than 5.0 mm, It was “ ⁇ ”.
- a PET fiber constituting the warp and weft of the inner layer of the tubular woven fabric As a PET fiber constituting the warp and weft of the inner layer of the tubular woven fabric, a microfiber drawn yarn having a single yarn fineness of about 0.31 dtex, a total fineness of 44 dtex, and 144 filaments (extension recovery rate at 20% elongation of 25%, 10% elongation recovery rate 40%), and the outer layer warp PET single filament fineness of about 2.33 dtex, total weaving 56 dtex, 24 filaments multifilament false twisted yarn (20% when stretched) A PET monofilament with a total weaving degree of 180 dtex (thickness 130 ⁇ m (single yarn side surface on Keyence microscope VHX-2000) is used as the weft yarn of the outer layer. Example), except that the number of wefts driven was 240 / cm. It was produced in the same manner as the tubular woven structure to those described.
- Comparative Example 2 As a PET fiber constituting the warp and weft of the inner layer of the tubular woven fabric, a microfiber false twisted yarn having a single yarn fineness of about 0.31 dtex, a total fineness of 44 dtex, and 144 filaments (elongation recovery rate at 20% elongation of 25%, A tubular woven fabric similar to that described in Comparative Example 1 was produced except that the elongation recovery rate at 10% elongation was 40%) and the number of wefts was 167 / cm.
- the kink resistance, tensile properties, cover factor, water permeability, and blood leakage of this tubular fabric were evaluated. The results are shown in Table 1, Table 2, and Table 3. Although it had the kink resistance, water permeability, and blood leakage resistance required for an artificial blood vessel, it was rigid and did not have stretchability.
- PET / PPT bimetal composite multifilament false twist yarn having the single yarn fineness of about 2.33 dtex, the total weaving degree of 56 dtex, and the number of filaments of 24 (the same yarn as the warp of Example 1) as the fibers constituting the weft of the inner layer of the tubular woven fabric ) was used during weaving, and a tubular woven fabric similar to that described in Example 1 was produced except that the number of wefts driven was 220 / cm.
- Comparative Example 4 The number of wefts driven during weaving in Comparative Example 3 is 220 / cm, but the same tube as described in Comparative Example 3 except that the number of wefts driven during weaving in Comparative Example 4 was 135 / cm. A woven fabric was prepared.
- Example 12 An artificial blood vessel (sample 12) in which no antithrombogenic material layer was formed on the multi-tubular fabric structure of Example 1 was obtained.
- the obtained artificial blood vessel (sample 12) was subjected to antithrombogenicity evaluation and cell affinity evaluation by an artificial blood vessel transplantation test into a canine carotid artery.
- the results are shown in Table 4.
- Table 4 in the antithrombogenicity evaluation, since complete occlusion was observed by the 28th day of transplantation, it was “x”, and in the cell affinity evaluation, the transfer of vascular endothelial cells was less than 2.0 mm, and “x” there were.
- the tubular woven fabric structure of the present invention is suitable for fluids, powder transfer, and hose for protecting linear objects such as wires, cables, and conduits, tubular filters, and artificial blood vessel substrates.
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Abstract
Description
また、特許文献2の筒状体についても、流体や粉体を移送する際に漏れが発生したりするため、内面を水密処理する必要があった。
また、人工血管に用いる場合も、漏血対策として、特許文献3で開示された方法を布製の人工血管に用いる場合、繊維の表面に付与したヘパリン又はヘパリン誘導体を含むコラーゲンやゼラチン等をコーティングする必要があった。
(1)経糸と緯糸とを交錯させて筒状に製織された筒状織物構造体であって、経糸の少なくとも一部が単糸繊度1.0dtex以上の弾性繊維であり、緯糸の少なくとも一部が単糸繊度1.0dtex未満のマイクロファイバーである筒状織物構造体。
(2)経糸のカバーファクターをCfaとし、緯糸のカバーファクターをCfbとした場合、Cfa<Cfbである(1)に記載の筒状織物構造体。
(3)筒状織物構造体の経方向の筒状織物構造体幅1mmあたり3.3N荷重時の伸度が4%以上であり、破断伸度が50%以下である(1)または(2)に記載の筒状織物構造体。
(4)前記単糸繊度1.0dtex以上の弾性繊維の単糸が熱収縮特性の異なる2種類のポリマーから構成される複合断面繊維である(1)ないし(3)のいずれかに記載の筒状織物構造体。
(5)熱収縮特性の異なる2種類のポリマーが、ポリエチレンテレフタレートおよびポリトリメチレンテレフタレートである(4)に記載の筒状織物構造体。
(6)筒状織物構造体が2以上の層からなるものである(1)ないし(5)のいずれかに記載の筒状織物構造体。
(7)最内層を除く層の緯糸の少なくとも一部が太さ20μm以上のモノフィラメントである(6)に記載の筒状織物構造体。
(8)筒状織物構造体の内表面での透水性が500mL(ミリリットル)/min/120mmHg(16kPa)/cm2以下である(1)ないし(7)のいずれかに記載の筒状織物構造体。
(9)(1)ないし(8)のいずれかに記載の筒状織物構造体を基材として用いた人工血管。
(10)血液と接触する筒状織物の内側に抗血栓性材料が結合することによって形成される抗血栓性材料層の厚さが1~600nmである(9)に記載の人工血管。
(11)上記抗血栓性材料は、硫黄原子を含むアニオン性の抗凝固活性を有する化合物を含む(10)に記載の人工血管。
(12)X線光電子分光法(XPS)で測定した内表面の全原子の存在量に対する硫黄原子の存在比率が3.0~6.0原子数%である(10)または(11)に記載の人工血管。
(13)X線光電子分光法(XPS)で測定した内表面の全原子の存在量に対する窒素原子の存在比率が、6.0~12.0原子数%である(10)ないし(12)のいずれかに記載の人工血管。
(14)上記抗血栓性材料は、アルキレンイミン、ビニルアミン、アリルアミン、リジン、プロタミン及びジアリルジメチルアンモニウムクロライドからなる群から選択される化合物を構成モノマーとして含むカチオン性ポリマー、を含み、上記カチオン性ポリマーは筒状織物を構成する経糸及び緯糸と共有結合している(10)~(13)のいずれかに記載の人工血管。
(15)上記抗血栓性材料は、エチレングリコール、プロピレングリコール、ビニルピロリドン、ビニルアルコール、ビニルカプロラクタム、酢酸ビニル、スチレン、メチルメタクリレート、ヒドロキシエチルメタクリレート及びシロキサンからなる群から選択される化合物を構成モノマーとして含む親水性ポリマーの骨格構造、4-(アミノメチル)ベンゼンカルボキシイミダミド又はベンゼンアミジンの骨格構造及びメトキシベンゼンスルホン酸アミドの骨格構造からなる3種類の骨格構造を含む化合物であり、上記3種類の骨格構造を含む化合物は筒状織物を構成する経糸及び緯糸と共有結合している(10)に記載の人工血管。
(16)上記3種類の骨格構造を含む化合物は、以下の一般式(I)~(IV)で示されるいずれかの化合物である、(15)に記載の人工血管。
(17)上記抗血栓性材料は、アクリル酸、メタクリル酸、α-グルタミン酸、γ-グルタミン酸及びアスパラギン酸からなる群から選択される化合物を構成モノマーとして含むアニオン性ポリマー、又は、シュウ酸、マロン酸、コハク酸、フマル酸、グルタル酸、アジピン酸、ピメリン酸、スベリン酸、アゼライン酸、セバシン酸、リンゴ酸、酒石酸及びクエン酸からなる群から選択されるアニオン性化合物を含む(10)~(16)のいずれかに記載の人工血管。
経糸の少なくとも一部に単糸繊度が1.0dtex以上の弾性繊維を含むことにより、筒状織物構造体の機械的強度を向上させるだけでなく、伸縮性と柔軟性のある筒状織物となり、耐キンク性等の物理特性も向上させることができる。なお、経糸に単糸繊度が1.0dtex以上の弾性繊維が含まれないと、筒状織物の機械的強度だけでなく、伸縮性や柔軟性が低下する傾向にある。特に長期的な使用が想定される場合において、使用する繊維の原料ポリマーにより生じ得る加水分解による強度劣化や、クリープ変形による伸縮性や柔軟性の低下があったとしても優れた強度や伸縮性、柔軟性を維持しうる点で、経糸の少なくとも一部に単糸繊度が2.0dtex以上の弾性繊維を含むことが好ましい。また、柔軟性の点から単糸繊度は5.0dtex以下であることが好ましく、3.0dtex以下であることがより好ましい。
総繊度が5dtex以上であると繊維が細過ぎることがなく、十分な強度や伸縮性が得られる。一方、200dtex以下であることで繊維が太過ぎず、筒状織物構造体に優れた柔軟性を付与することができる。
好ましい具体例としては、スパンデックス繊維、熱収縮特性の異なる2種類のポリマーから構成される複合断面繊維が挙げられる。
緯糸の少なくとも一部に単糸繊度が1.0dtex未満のマイクロファイバーを含むことにより、筒状織物構造体の柔軟性が向上するだけでなく、単糸が細く、単糸間の空隙を小さくできるので、透水性を低くすることが可能である。ここでマイクロファイバーとは単糸繊度1.0dtex未満の繊維を指す。かかるマイクロファイバーはマルチフィラメントの形態で用いるのが好ましい。
緯糸に単糸繊度が1.0dtex以上のマルチフィラメントのみを使用しても、織密度を高くすれば透水性を低くすることができるが、筒状織物構造体が硬くなり、柔軟性や伸縮性が損なわれてしまう。織物構造体が硬くなるとキンクの原因や、内層面での凹凸が発生する原因となり、好ましくない。
本発明の筒状織物構造体を、人工血管に使用する場合、緯糸に単糸繊度が1.0dtex未満のマイクロファイバーを含むため、繊維間空隙は減少し、より漏血性を抑制出来る。また、それに加え、血管内皮細胞が付着するに適した足場の数が極めて多いので、血管内皮細胞と人工血管内層構成繊維との馴染みがよく、血管内皮細胞の人工血管内層への張付き性が良好となるので、生体親和性の高い人工血管を得ることができる。人工血管に用いるマイクロファイバーは、単糸繊度が1.0dtex未満であり、更に好ましくは、単糸繊度0.50dtex以下である。また、単糸繊度が0.008dtex以上であれば、細胞の付着性が優れる点で好ましい。また、総繊度は、5dtex以上、200dtex以下が好ましい。
総繊度が5dtex未満であると繊維が細過ぎて、十分な強度が得られない。一方、200dtexを超えると繊維が太過ぎて、筒状織物構造体の柔軟性が損なわれるため、耐キンク性が低下する懸念がある。
織物構造体を人工血管に使用する場合、生体内には、一定程度の高い血圧が存在するため、繊維間隙から血液の漏れが生じることは避けがたい。そこで、血管外科手術に布製の人工血管を使用するに当たっては、植込み直前に人工血管を血液に触れさせて、繊維間隙に血栓を人為的に作らせ、この血栓によって繊維間隙を一時的に目詰まりさせる操作、いわゆるプレクロッティングが行われることが多い。
しかしながら、最近の外科手術では血液の凝固を防ぐ目的でヘパリンを使用することが多いことから、プレクロッティング操作による目詰まりが不完全になることが多く、血液の漏れに起因する手術後の大量出血という危険な状態も生じうる。加えて、手術後に自然現象である線維素溶解現象によってプレクロッティングにより生じたフィブリンが溶け始める状態が発生すると、血液凝固組織は容易に破壊されてしまう。
血液凝固は、フィブリンの析出と血小板の凝集とからスタートするが、上記したように、フィブリンの析出はヘパリンや線維素溶解現象の影響を受けるため、これらの影響を受け難い血小板の凝集という経路を活用するために、繊維径に着目した。
経糸のカバーファクターをCfaとし、緯糸のカバーファクターをCfbとした場合、Cfa<Cfbであることが好ましい。カバーファクターは繊維間の繊維の隙間の程度(充填密度)を表し、小さいほど繊維の隙間が広いことを示す。そこで、本発明の筒状織物構造体のカバーファクターは、経糸のカバーファクターCfa<緯糸のカバーファクターCfbであれば、マイクロファイバーの占める面積が大きく、透水性や漏血性を低くコントロールできるので好ましい。
なお、カバーファクターは後述の方法で測定される値である。
本発明においては、ストレッチ性の点から筒状織物構造体の経方向の筒状織物構造体幅1mmあたり3.3N/荷重時の伸度が、4%以上であることが好ましく、4.5%以上であることがより好ましい。また、上限は、15%以下であることが好ましく、10%以下であることがより好ましい。なお、筒状織物構造体の経方向の筒状織物構造体幅1mmあたり3.3N/荷重時の伸度は後述する方法により測定されるものである。
また、筒状織物構造体の破断伸度が50%以下であれば、寸法安定性とストレッチ性を両立し、柔軟性に優れるので好ましく、40%以下であることがより好ましい。また、柔軟性の点から10%以上であることが好ましく、20%以上であることがより好ましい。
熱収縮特性の異なる2種類のポリマーから構成される複合断面繊維におけるポリマーとしては、熱収縮特性の異なる2種類のポリエステルが好ましく挙げられる。組み合わせとしては粘度の異なるポリエステル(例えばポリトリメチレンテレフタレートなど)、ポリトリメチレンテレフタレートとその他のポリマエステル(例えばポリエチレンテレフタレート、ポリブチレンテレフタレートなど)を組み合わせることが好ましい。なかでも一方の成分がポリエチレンテレフタレート(PET)を主体とするポリエステルであって、他方の成分がポリトリメチレンテレフタレート(PTT)を主体とするポリエステルであることが好ましい。
本発明においては上記2成分が繊維長さ方向に沿ってサイドバイサイド型または偏心芯鞘型に複合された繊維から構成されることが好ましい。このような複合糸を仮撚加工や熱処理することにより、コイル捲縮を発現させることできるため、優れた伸縮性を得ることができるため、好ましい。
本発明においては筒状織物構造体を2以上の層から構成することで、筒状織物構造体の最内層部を外力から保護し、耐久性が向上するため、流体、粉体移送に用いる際の液体や粉体の漏れを防止し、又、ワイヤ、ケーブル、電線管等の線状物を保護する機能を向上させることができるので、好ましい。
また、特に人工血管の基材に用いる場合は、内側が血液と接触する構造とする。また、人工血管の基材に用いる場合、血液と接触する筒状織物の内側を内層筒状織物とし、人工血管の外層を形成する筒状織物の外側を外層筒状織物とし、外層筒状織物と内層筒状織物が重ねられた構造を、多重筒状織物構造とすることが好ましい。さらに、本発明の人工血管を構成する多重筒状織物構造は、内層筒状織物と外層筒状織物以外の筒状織物層を含んでいてもよいが、筒状織物層の数が多すぎると、人工血管の厚みが厚くなるため生体血管の厚みとの乖離が大きくなり、移植手術の際の吻合等の作業性が低下する。このため、筒状織物層の数は2~4が好ましく、2~3がより好ましい。
なお、2層以上の多重織物構造にする場合の緯糸は、少なくとも一部が単糸繊度1.0dtex未満のマイクロファイバーであれば特に限定する必要はなく、用途によって、種々の合成樹脂からなる合成繊維を選択して使用でき、形態もマルチフィラメントやモノフィラメントなど、適宜選択することができる。特に人工血管の基材に用いる場合には、内層表面側に単糸繊度1.0dtex未満のマイクロファイバーが配されていることが好ましい。
本発明の筒状織物構造体は、屈曲されたり、蛇行状に配置されることがある。本発明の筒状織物構造体は、キンク性に優れるため、潰れ、ねじれが発生しにくいが、よりいっそうの耐キンク性(易屈曲性)を備えることが好ましい。そのためには、最内層を除く層の緯糸の少なくとも一部に太さ20μm以上のモノフィラメントを使用することが好ましい。剛性の強い太さ20μm以上のモノフィラメントからなる緯糸は筒状織物構造体に、より優れた耐キンク性を与えるので好ましい。
より好ましい太さとしては100μm以上である。上限としては柔軟性の点から300μm以下とすることが好ましく、更に好ましくは200μm以下とすることがより好ましい。
透水性が高すぎると、繊維間隙のサイズや量が大きいことにより、流体、粉体移送用ホースに用いる場合、液体や粉体の漏れが多すぎる。また、人工血管に用いる場合は、漏血量が多くなる傾向になる。したがって、透水性は小さい方が好ましい。
本発明においては、内表面での透水性が500mL(ミリリットル)/min/120mmHg(16kPa)/cm2以下であることが好ましく、さらには200mL/min/120mmHg/cm2以下であることがより好ましく、更に好ましくは150mL/min/120mmHg/cm2以下であることがさらにより好ましい。
一般に筒状織物を人工血管として使用する場合、移植した際に生体はこれを異物として認識し、特に人工血管の血液との接触面、すなわち内表面では血液凝固反応が進行して血栓が形成されるため、抗血栓処理されていることが好ましい。従来、医用材料の抗血栓性を向上する方法としては、ヘパリン又はヘパリン誘導体を材料の表面に付与する手法が用いられてきた。しかしながら、人工血管を構成するポリエステル繊維等の布製の医用材料、延伸多孔質ポリテトラフルオロエチレン(以下、「ePTFE」)製の医用材料には、ヘパリン又はヘパリン誘導体を直接付与することができない。そのため、医用材料の表面を改質させた後、共有結合でヘパリン又はヘパリン誘導体を材料の表面に付与させる方法(特許文献11~13)や、イオン結合でヘパリン又はヘパリン誘導体を材料の表面に付与させる方法(特許文献14~17)が報告されている。
抗血栓性とは、血液と接触する表面で血液が凝固しない性質であり、例えば、血小板の凝集や、トロンビンに代表される血液凝固因子の活性化などで進行する血液凝固を阻害する性質を指す。ここで、細胞親和性とは、生体血管の内表面に存在し血栓形成を阻害することができる血管内皮細胞が定着し、内膜が形成しやすい性質を指す。
[測定条件]
装置 :電界放出型透過電子顕微鏡JEM-2100F(JEOL社製)
EELS検出器 :GIF Tridiem(GATAN社製)
EDX検出器 :JED-2300T(JEOL社製)
画像取得 :Digital Micrograph(GATAN社製)
試料調整 :超薄切片法(銅製マイクログリッドに懸架し、包埋樹脂はアクリル系樹脂を使用。)
加速電圧 :200kV
ビーム径 :直径0.7nm
エネルギー分解能 :約1.0eVFWHM
[測定条件]
装置 :ESCALAB220iXL(VG Scientific社製)
励起X線 :monochromaticAlKα1,2線(1486.6eV)
X線径 :1mm
X電子脱出角度 :90°(人工血管の表面に対する検出器の傾き)
・・・式2
分割ratio : 各分割ピーク成分の存在比率(%)
N1sratio : 全原子の存在量に対する窒素原子の存在比率(%)
分割percent : N1sピークにおける各分割ピーク成分の存在比率(%)
・・・式3
分割ratio : 各分割ピーク成分の存在比率(%)
C1sratio : 全原子の存在量に対する炭素原子の存在比率(%)
分割percent : C1sピークにおける各分割ピーク成分の存在比率(%)
[測定条件]
装置 :TOF.SIMS5(ION-TOF社製)
1次イオン種 :Bi3 ++
2次イオン極性 :正および負
質量範囲(m/z) :0~1500
ラスターサイズ :300μm四方
ピクセル数(1辺) :256ピクセル
後段加速 :10kV
測定真空度(試料導入前) :4×10-7Mpa
1次イオン加速電圧 :25kV
パルス幅 :10.5ns
バンチング :あり(高質量分解能測定)
帯電中和 :あり
(1)総繊度・単糸繊度
JIS L 1013 (2010) 8.3.1 A 法に従って、所定荷重0.045[cN/dtex]で正量繊度を測定して総繊度とし、それを単繊維数で除することで単糸繊度を算出した。
(2)伸長率、伸長回復率
糸一本をつかみ間隔20cmで、0.1g/デシテックスの荷重(初荷重)をかけながら、引張試験機に取り付け、引張速度20cm/minで所定の伸度(a)まで引張り(すなわちa%伸長した)、1分間その状態を保持した後、初期のつかみ間隔(20cm)になるまでつかみ間隔を戻す。このときの、荷重が0Nになったときの、糸の伸度(b)を引張試験時のS-S曲線から求め、下記の式で求めた。測定は3回行い、平均値を求めた。
伸長率(%)=a (a=10%、20%でそれぞれ測定を行った)
a%伸長時の伸長回復率(%)=(a-b)÷a×100
カバーファクター(CF)は経糸或いは緯糸に用いる糸の総繊度と基布密度から計算される値であり、経糸総繊度をDw (dtex)、緯糸総繊度をDf (dtex)、経糸の基布密度をNw (本/2.54cm)、緯糸の基布密度をNf(本/2.54cm)としたとき、次式で表される。
経方向のカバーファクターCFa=Dw1/2×Nw
緯方向のカバーファクターCFb=Df1/2×Nf
なお、基布密度は、作製した筒状織物構造体を円筒の長さ方向に切開して、その内壁表面をキ一エンス製マイクロスコープVHX‐2000にて50倍に拡大した写真をもとに、計測した。
IS07198のガイダンスに則り、耐キンク性はキンク半径を測定した。筒状織物構造体をループさせていき、外観上明らかに折れ曲がりが生じた半径を半径既知の円筒状治具を用いて測定した。織成管状体自体の特性を評価するため、内圧維持は行わなかった。
(5)筒状織物構造体の幅
筒状織物構造体の長さ方向に垂直に金属製定規を押し当て、筒状織物断面を押し潰して、織物幅を測定する。測定は、筒状織物構造体の無作為に選択した場所3箇所を各1回行い、平均値を求めた。
〔破断強度、破断伸度、筒状織物構造体幅1mmあたり3.3N荷重時の伸度〕
JIS L1096 A法 カットストリップ法に準じて測定した。
作製した筒状織物構造体を、つかみ間隔10cmで、引張試験機に取り付け、引張速度20cm/minで測定し、引張試験時のS-S曲線から、筒状織物構造体幅1mmあたり3.3N荷重時の伸度と、試験片が破断したときの荷重と伸度を求めた。
筒状織物構造体の両端部のうち、片側を塞いだ状態で、もう一方の片側に25℃の水道水程度の充分綺麗な水を多重筒状織物構造体の内壁に、120mmHg(16kPa)の水圧がかかるように、20分間通過させ、その後に筒状織物構造体の壁面より1分間で漏出する漏水量を測定し、この測定に用いた多重筒状織物構造体の表面積(cm2)で除した値とする。測定は3回行い、平均値を求めた。
筒状織物構造体の両端部のうち、片側を塞いだ状態で、もう一方の片側に25℃の牛血液を含むチューブ類を設置し、筒状織物構造体の内側にかかる圧力が120mmHg(16kPa)となるような条件下で人工血管全体が十分含浸するまで20分間内側から外側に向けて牛血液を通した後、5~20分間の通液量(mL)を採取した。その通液量(mL)を人工血管の内表面積(cm2)および単位時間(min)で除した値を、120mmHg(16kPa)における漏血量とした。測定は3回行い、平均値を求めた。
STEMによって、抗血栓性材料層の厚みを評価した。人工血管の断面試料を超薄切片法で作製してから、下記条件でSTEM-EDX法を用いて抗血栓性材料由来の硫黄原子が観測される厚み、STEM-EELS法を用いて抗血栓性材料由来の窒素原子が観測される厚みを分析した。ここでいう平均の厚みは、無作為に抽出した少なくとも3点の平均の値を指す。
[測定条件]
装置 :電界放出型透過電子顕微鏡JEM-2100F(JEOL社製)
EELS検出器 :GIF Tridiem(GATAN社製)
EDX検出器 :JED-2300T(JEOL社製)
画像取得 :Digital Micrograph(GATAN社製)
試料調整 :超薄切片法(銅製マイクログリッドに懸架し、包埋樹脂はアクリル系樹脂を使用。)
加速電圧 :200kV
ビーム径 :直径0.7nm
エネルギー分解能 :約1.0eVFWHM
P.C.Begovacらの文献(Eur Vasc Endovasc Surg 25, 432-437 2003)等を参考にして、イヌ頚動脈に人工血管を移植した。定期的に、移植した人工血管及び両側の生体血管の超音波エコーや血管造影を実施し、血栓の有無や閉塞の有無を確認した。移植28日後に完全閉塞が見られなければ、抗血栓性が高いとして「○」、完全閉塞していれば、抗血栓性が不足しているとして「×」と判定した。
評価2と同様にして、イヌ頚動脈に人工血管を移植した。移植28日後に人工血管を摘出し、H.E.染色した標本を作成した。得られた標本を顕微鏡で観察し、人工血管と生体血管の縫合部から血管内皮細胞が移入して定着した部分までの長さを測定した。血管内皮細胞が移入した長さが5.0mm以上であれば、細胞親和性がより高いとして「◎」、移入した長さが2.0mm以上、5.0mm未満であれば、細胞親和性が高いとして「○」、
移入した長さが2.0mm未満であれば細胞親和性が不足しているとして「×」と判定した。
筒状織物の内層および外層の経糸として単糸繊度が約2.33dtex、総織度56dtex、フィラメント数24本のPETとPPTを用いたサイドバイサイド型の断面形状を有する複合断面繊維の仮撚加工糸(PET/PPTバイメタル-DTY糸、20%伸長時の伸長回復率45%、10%伸長時の伸長回復率60%)であるマルチフィラメント(弾性繊維)を使用し、筒状織物の内層の緯糸として、単糸繊度が約0.31dtex、総織度44dtex、フィラメント数144本のPETマイクロファイバー仮撚糸を使用し、外層の緯糸として、総織度180dtexのPETモノフィラメント(太さ130μm(単糸側面をキーエンス製マイクロスコープVHX-2000にて400倍に拡大した写真をもとに測定))を使用した。
筒状織物構造体の内層の緯糸として、単糸繊度が約0.08dtex、総織度52.8dtex、フィラメント数630本のPETマイクロファイバーを準備し、これを製織時に使用し、緯糸打ち込み本数を186本/cmにした以外は、実施例1記載のものと同様の筒状織物を作製した。
実施例1における製織時の緯糸打ち込み本数は202本/cmであるが、この実施例3における製織時の緯糸打ち込み本数を158本/cmとした以外は、実施例1記載のものと同様の筒状織物を作製した。
実施例2における製織時の緯糸打ち込み本数は186本/cmであるが、この実施例4における製織時の緯糸打ち込み本数を125本/cmとした以外は、実施例2記載のものと同様の筒状織物を作製した。
実施例1の筒状織物構造体を5.0重量%過マンガン酸カリウム(和光純薬工業株式会社製)、0.6mol/L硫酸(和光純薬工業株式会社製)の水溶液に浸漬し、60℃で3時間反応させて筒状織物構造体を加水分解及び酸化した。
実施例1の筒状織物構造体を用いて、実施例5と同様の操作を行い、加水分解及び酸化し、PEIを縮合反応により共有結合させた後、0.5重量%DMT-MM、40重量%無水コハク酸(和光純薬工業株式会社製)のジメチルアセトアミドに浸漬し、50℃で17時間反応させた。
実施例1の筒状織物構造体を用いて、実施例5と同様の操作を行い、加水分解及び酸化し、PEIを縮合反応により共有結合させた後、0.5重量%DMT-MM、0.5重量%PAA(ポリアクリル酸、重量平均分子量100万;和光純薬工業株式会社製)の水溶液に浸漬し、30℃で2時間反応させた。
実施例7と同様の操作を行い、PEIをポリアリルアミン塩酸塩(以下、「PAH」)(重量平均分子量90万;シグマ-アルドリッチ社製)に変更した人工血管を得るとともに、PEIをポリ-L-リシン臭化水素酸塩(以下、PLys)(重量平均分子量3~7万;シグマ-アルドリッチ社製)に変更した人工血管を得た。
実施例5と同様の操作を行い、ヘパリンナトリウムをデキストラン硫酸ナトリウム(和光純薬工業株式会社製)に変更して、抗血栓性材料層を形成した人工血管(試料6)を得た。
実施例1の筒状織物構造体について、実施例5と同様の操作を行い、加水分解及び酸化した後、1.0重量%化合物A(以下の一般式(X))、化合物Aに対して2モル等量の水酸化ナトリウム及び3モル等量のDMT-MMを溶解させた水溶液に浸漬し、30℃で2時間反応させて筒状織物1に化合物Aを縮合反応により共有結合させて抗血栓性材料層を形成した人工血管(試料7)を得た。
実施例10と同様の操作を行い、化合物Aを化合物B(以下の一般式(XI))、化合物C(以下の一般式(XII))、及び化合物D(以下の一般式(XIII))に変更した人工血管をそれぞれ得た。
実施例1の筒状織物構造体について、実施例5と同様の操作を行い、加水分解及び酸化し、PEIを縮合反応により共有結合させた後、0.5重量%DMT-MM、0.5重量%PAA(重量平均分子量100万;和光純薬工業株式会社製)の水溶液に浸漬し、30℃で2時間反応させた。
筒状織物の内層の経糸および緯糸を構成するPET繊維として、単糸繊度が約0.31dtex、総繊度44dtex、フィラメント数144本のマイクロファイバー延伸糸(20%伸長時の伸長回復率25%、10%伸長時の伸長回復率40%)を使用し、外層の経糸として、単糸繊度が約2.33dtex、総織度56dtex、フィラメント数24本のPETマルチフィラメント仮撚糸(20%伸長時の伸長回復率25%、10%伸長時の伸長回復率40%)を使用し、外層の緯糸として、総織度180dtexのPETモノフィラメント(太さ130μm(単糸側面をキーエンス製マイクロスコープVHX-2000にて400倍に拡大した写真をもとに測定))を使用し、緯糸打ち込み本数を240本/cmにした以外は、実施例1記載のものと同様の筒状織物構造体を作製した。
筒状織物の内層の経糸および緯糸を構成するPET繊維として、単糸繊度が約0.31dtex、総繊度44dtex、フィラメント数144本のマイクロファイバー仮撚糸(20%伸長時の伸長回復率25%、10%伸長時の伸長回復率40%)を使用し、緯糸打ち込み本数を167本/cmにした以外は、比較例1記載のものと同様の筒状織物を作製した。
筒状織物の内層の緯糸を構成する繊維として、単糸繊度が約2.33dtex、総織度56dtex、フィラメント数24本のPET/PPTバイメタル複合マルチフィラメント仮撚糸(実施例1の経糸と同じ糸)を準備し、これを製織時に使用し、緯糸打ち込み本数を220本/cmにした以外は、実施例1記載のものと同様の筒状織物を作製した。
比較例3における製織時の緯糸打ち込み本数は220本/cmであるが、この比較例4における製織時の緯糸打ち込み本数を135本/cmとした以外は、比較例3記載のものと同様の筒状織物を作製した。
実施例1の多重筒状織物構造体に、何も抗血栓性材料層を形成させない人工血管(試料12)を得た。
Claims (17)
- 経糸と緯糸とを交錯させて筒状に製織された筒状織物体であって、経糸の少なくとも一部が単糸繊度1.0dtex以上の弾性繊維であり、緯糸の少なくとも一部が単糸繊度1.0dtex未満のマイクロファイバーである筒状織物構造体。
- 経糸のカバーファクターをCfaとし、緯糸のカバーファクターをCfbとした場合、Cfa<Cfbである請求項1に記載の筒状織物構造体。
- 筒状織物構造体の経方向の筒状織物構造体幅1mm当たりの3.3N荷重時の伸度が4%以上であり、破断伸度が50%以下である請求項1または2に記載の筒状織物構造体。
- 前記単糸繊度1.0dtex以上の弾性繊維の単糸が熱収縮特性の異なる2種類のポリマーから構成される複合断面繊維である請求項1ないし請求項3のいずれかに記載の筒状織物構造体。
- 熱収縮特性の異なる2種類のポリマーが、ポリエチレンテレフタレートおよびポリトリメチレンテレフタレートである請求項4に記載の筒状織物構造体。
- 筒状織物構造体が2以上の層からなる請求項1ないし請求項5のいずれかに記載の筒状織物構造体。
- 最内層を除く層の緯糸の少なくとも一部が太さ20μm以上のモノフィラメントである請求項6に記載の筒状織物構造体。
- 筒状織物構造体の内表面での透水性が500mL(ミリリットル)/min/120mmHg(16kPa)/cm2以下である請求項1ないし請求項7のいずれかに記載の筒状織物構造体。
- 請求項1ないし請求項8のいずれかに記載の筒状織物構造体を基材とする人工血管。
- 血液と接触する筒状織物の内側に抗血栓性材料が結合することによって形成される抗血栓性材料層の厚さが1~600nmである請求項9に記載の人工血管。
- 上記抗血栓性材料は、硫黄原子を含むアニオン性の抗凝固活性を有する化合物を含む請求項10に記載の人工血管。
- X線光電子分光法(XPS)で測定した内表面の全原子の存在量に対する硫黄原子の存在比率が3.0~6.0原子数%である請求項10または11に記載の人工血管。
- X線光電子分光法(XPS)で測定した内表面の全原子の存在量に対する窒素原子の存在比率が、6.0~12.0原子数%である請求項10ないし請求項12のいずれかに記載の人工血管。
- 上記抗血栓性材料は、アルキレンイミン、ビニルアミン、アリルアミン、リジン、プロタミン及びジアリルジメチルアンモニウムクロライドからなる群から選択される化合物を構成モノマーとして含むカチオン性ポリマー、を含み、上記カチオン性ポリマーは筒状織物を構成する経糸及び緯糸と共有結合している請求項10ないし請求項13のいずれかに記載の人工血管。
- 上記抗血栓性材料は、エチレングリコール、プロピレングリコール、ビニルピロリドン、ビニルアルコール、ビニルカプロラクタム、酢酸ビニル、スチレン、メチルメタクリレート、ヒドロキシエチルメタクリレート及びシロキサンからなる群から選択される化合物を構成モノマーとして含む親水性ポリマーの骨格構造、4-(アミノメチル)ベンゼンカルボキシイミダミド又はベンゼンアミジンの骨格構造及びメトキシベンゼンスルホン酸アミドの骨格構造からなる3種類の骨格構造を含む化合物であり、上記3種類の骨格構造を含む化合物は筒状織物を構成する経糸及び緯糸と共有結合している請求項10に記載の人工血管。
- 上記抗血栓性材料は、アクリル酸、メタクリル酸、α-グルタミン酸、γ-グルタミン酸及びアスパラギン酸からなる群から選択される化合物を構成モノマーとして含むアニオン性ポリマー、又は、シュウ酸、マロン酸、コハク酸、フマル酸、グルタル酸、アジピン酸、ピメリン酸、スベリン酸、アゼライン酸、セバシン酸、リンゴ酸、酒石酸及びクエン酸からなる群から選択されるアニオン性化合物を含む請求項10ないし請求項16のいずれかに記載の人工血管。
Priority Applications (10)
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AU2016266324A AU2016266324A1 (en) | 2015-05-27 | 2016-05-19 | Tubular woven fabric structure |
CA2985599A CA2985599A1 (en) | 2015-05-27 | 2016-05-19 | Tubular woven construct |
US15/576,031 US20180147044A1 (en) | 2015-05-27 | 2016-05-19 | Tubular woven construct |
RU2017145597A RU2017145597A (ru) | 2015-05-27 | 2016-05-19 | Трубчатая тканая конструкция |
EP16799908.5A EP3305336A4 (en) | 2015-05-27 | 2016-05-19 | TUBULAR WOVEN STRUCTURE |
JP2017520656A JPWO2016190202A1 (ja) | 2015-05-27 | 2016-05-19 | 筒状織物構造体 |
KR1020177031861A KR20180012748A (ko) | 2015-05-27 | 2016-05-19 | 통형상 직물 구조체 |
MX2017014997A MX2017014997A (es) | 2015-05-27 | 2016-05-19 | Construccion tejida tubular. |
BR112017025041A BR112017025041A2 (pt) | 2015-05-27 | 2016-05-19 | construto de tecido tubular |
CN201680030696.XA CN107614024A (zh) | 2015-05-27 | 2016-05-19 | 筒状织物结构体 |
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JP2015-108022 | 2015-05-27 | ||
JP2015108022 | 2015-05-27 |
Publications (1)
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PCT/JP2016/064811 WO2016190202A1 (ja) | 2015-05-27 | 2016-05-19 | 筒状織物構造体 |
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US (1) | US20180147044A1 (ja) |
EP (1) | EP3305336A4 (ja) |
JP (1) | JPWO2016190202A1 (ja) |
KR (1) | KR20180012748A (ja) |
CN (1) | CN107614024A (ja) |
AU (1) | AU2016266324A1 (ja) |
BR (1) | BR112017025041A2 (ja) |
CA (1) | CA2985599A1 (ja) |
MX (1) | MX2017014997A (ja) |
RU (1) | RU2017145597A (ja) |
WO (1) | WO2016190202A1 (ja) |
Cited By (3)
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JP2019157321A (ja) * | 2018-03-16 | 2019-09-19 | Kbセーレン株式会社 | ストレッチ性布帛 |
CN111655917A (zh) * | 2018-01-30 | 2020-09-11 | 东丽株式会社 | 平纹织物、其制造方法及支架移植体 |
JPWO2021117894A1 (ja) * | 2019-12-13 | 2021-06-17 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JP7021719B2 (ja) * | 2019-10-31 | 2022-02-17 | 東レ株式会社 | 液体ろ過用フィルタ |
US20230243073A1 (en) * | 2020-08-27 | 2023-08-03 | Sanexen Environmental Services Inc. | Tubular woven liner |
CN112842618B (zh) * | 2021-01-06 | 2023-05-12 | 北京理工大学 | 一种小口径可降解复合人工血管及其制备方法 |
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- 2016-05-19 JP JP2017520656A patent/JPWO2016190202A1/ja active Pending
- 2016-05-19 EP EP16799908.5A patent/EP3305336A4/en not_active Withdrawn
- 2016-05-19 RU RU2017145597A patent/RU2017145597A/ru not_active Application Discontinuation
- 2016-05-19 CA CA2985599A patent/CA2985599A1/en not_active Abandoned
- 2016-05-19 US US15/576,031 patent/US20180147044A1/en not_active Abandoned
- 2016-05-19 KR KR1020177031861A patent/KR20180012748A/ko unknown
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CN111655917A (zh) * | 2018-01-30 | 2020-09-11 | 东丽株式会社 | 平纹织物、其制造方法及支架移植体 |
CN111655917B (zh) * | 2018-01-30 | 2022-09-06 | 东丽株式会社 | 平纹织物、其制造方法及支架移植体 |
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Also Published As
Publication number | Publication date |
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MX2017014997A (es) | 2018-04-11 |
EP3305336A4 (en) | 2019-01-09 |
CN107614024A (zh) | 2018-01-19 |
BR112017025041A2 (pt) | 2018-08-07 |
JPWO2016190202A1 (ja) | 2018-03-08 |
EP3305336A1 (en) | 2018-04-11 |
CA2985599A1 (en) | 2016-12-01 |
AU2016266324A1 (en) | 2017-11-16 |
US20180147044A1 (en) | 2018-05-31 |
KR20180012748A (ko) | 2018-02-06 |
RU2017145597A (ru) | 2019-06-27 |
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