WO2020054454A1 - Dispositif médical - Google Patents

Dispositif médical Download PDF

Info

Publication number
WO2020054454A1
WO2020054454A1 PCT/JP2019/033992 JP2019033992W WO2020054454A1 WO 2020054454 A1 WO2020054454 A1 WO 2020054454A1 JP 2019033992 W JP2019033992 W JP 2019033992W WO 2020054454 A1 WO2020054454 A1 WO 2020054454A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
compound
dry coating
coating film
surface layer
Prior art date
Application number
PCT/JP2019/033992
Other languages
English (en)
Japanese (ja)
Inventor
亮平 小口
創 江口
麗君 朱
今日子 山本
Original Assignee
Ａｇｃ株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ａｇｃ株式会社 filed Critical Ａｇｃ株式会社
Priority to JP2020545908A priority Critical patent/JP7334738B2/ja
Publication of WO2020054454A1 publication Critical patent/WO2020054454A1/fr

Links

Classifications

    • 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
    • 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
    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • 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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • 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
    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04—Macromolecular materials
    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/10—Inorganic materials
    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/06—Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B9/00—Layered products comprising a layer of a particular substance not covered by groups B32B11/00 - B32B29/00
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B9/00—Layered products comprising a layer of a particular substance not covered by groups B32B11/00 - B32B29/00
    • B32B9/04—Layered products comprising a layer of a particular substance not covered by groups B32B11/00 - B32B29/00 comprising such particular substance as the main or only constituent of a layer, which is next to another layer of the same or of a different material

Definitions

  • the present invention relates to a medical device, and more particularly, to a medical device such as a medical instrument, an artificial organ, or a cell culture container that includes a contact with a biological substance such as a cell and a protein when used.
  • a medical device such as a medical instrument, an artificial organ, or a cell culture container that includes a contact with a biological substance such as a cell and a protein when used.
  • Non-Patent Document 1 a polymer of 2-methacryloyloxyethyl phosphorylcholine (hereinafter also referred to as “MPC”) having a structure similar to a biological membrane or a synthetic polymer material such as a polymer containing polyoxyethylene glycol is used.
  • the formed coating layer is formed on the resin surface of the base material to enhance biocompatibility.
  • MPC is copolymerized with a hydrophobic monomer such as butyl methacrylate (Patent Document 1), and a hydrophilic polymer obtained by copolymerizing an epoxy group-containing monomer is reacted with an epoxy group to form a resin material surface. It has been proposed to increase the water resistance by immobilizing (for example, Patent Document 2).
  • Some medical tubes are inserted into a living body for a predetermined period of time, used, and then removed.
  • the surface of the medical tube is required to be non-adhesive to living organs.
  • the tube surface is made uneven, or the tube surface is coated with an adhesion suppressing layer.
  • Patent Document 4 As a method for producing a cell culture dish having a hydrophilic surface and improved wettability to a culture solution, a method of vacuum-depositing silicon oxide on the inner surface of a resin-made dish has been proposed (Patent Document 4). However, sufficient biocompatibility cannot be expected with a silicon oxide layer.
  • the present invention relates to a medical device having a biocompatible surface layer on a resin surface of a device substrate using a resin material. It is an object of the present invention to provide a medical device which is excellent in performance and does not cause deterioration of a device substrate in a manufacturing process.
  • the gist of the present invention is as follows. [1] At least one part of the surface of a device substrate made of a resin material, and at least one metal oxide provided on the surface made of the resin material and selected from the group consisting of silicon oxide, titanium oxide and aluminum oxide A dry coating film containing, as a main component, a surface layer formed on the dry coating film and having a biocompatible group and covalently bonded to the dry coating film, A medical device comprising: [2] The medical treatment according to [1], wherein when the surface layer is immersed in water at 40 ° C. for 7 days, the amount of total organic carbon (TOC) eluted in water per unit area of 1 cm 2 of the surface layer is 10 mg / L or less. For device. [3] The medical device according to [1] or [2], wherein the dry coating film is a deposited film.
  • TOC total organic carbon
  • the surface layer is any one of [1] to [3], which is a cured product of a composition containing a compound having the biocompatible group and a group capable of forming a covalent bond with the dry coating film.
  • Medical devices [5] The medical device according to [4], wherein the group capable of forming a covalent bond with the dry coating film is a hydrolyzable silyl group.
  • the biocompatible group includes at least one selected from the group consisting of a group represented by the following formula 1, a group represented by the following formula 2, and a group represented by the following formula 3,
  • the affinity group has a group represented by the following formula 1
  • 50 to 100 mol% of the group represented by the following formula 1 is the group represented by the formula 1 in the group represented by the following formula 4
  • the medical device according to any one of [1] to [7], wherein
  • n is an integer of 1 to 300.
  • R 1 to R 3 are each independently an alkyl group having 1 to 5 carbon atoms, and a is an integer of 1 to 5.
  • R 4 and R 5 are each independently an alkyl group having 1 to 5 carbon atoms, and X ⁇ is a group represented by the following formula 3-1 or a group represented by the following formula 3-2.
  • B is an integer of 1 to 5.
  • n is an integer of 1 to 300
  • R 6 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.
  • the surface layer is excellent in adhesion to the resin surface of the device substrate, and the biocompatibility is improved.
  • a compound or a group represented by a formula is also described as a compound or a group with the number of the formula.
  • a compound represented by the formula 1 is also described as a compound 1.
  • (Meth) acrylate is a generic term for acrylate and methacrylate.
  • the “unit” in the copolymer means a portion derived from the monomer formed by polymerization of the monomer.
  • Biocompatibility refers to a property of preventing a biological substance such as a cell and a protein from adhering and becoming immobile, in other words, a property of being inactive when the biological substance contacts.
  • Biocompatible group refers to a group having biocompatibility.
  • “Dry coating film” is a film obtained by dry coating.
  • a “medical device” is a device used for medical treatment, such as treatment, diagnosis, anatomy or biological examination, and is inserted or brought into contact with a living body such as a human body, or a medium (blood Etc.).
  • the medical device of the present invention includes a device substrate having at least a part of a surface made of a resin material, and at least one selected from the group consisting of silicon oxide, titanium oxide, and aluminum oxide provided on the surface made of the resin material.
  • a dry coating film mainly composed of a kind of metal oxide; and a surface layer provided on the dry coating film and having a biocompatible group and covalently bonded to the dry coating film.
  • the surface made of the resin material is also referred to as “resin surface”.
  • At least one metal oxide selected from the group consisting of silicon oxide, titanium oxide and aluminum oxide is also referred to as metal oxide (D).
  • the fact that the dry coating film contains the metal oxide (D) as a main component means that the content ratio of the metal oxide (D) in the dry coating film is 90 to 100% by mass.
  • a dry coating film containing a metal oxide (D) as a main component is provided between the resin surface of the device base material and the surface layer having a biocompatible group, whereby the biocompatibility is obtained.
  • the surface layer having a group is firmly fixed to the resin surface of the device substrate via the dry coating film.
  • dry coating for producing a dry coating film does not involve a treatment that causes deterioration of the resin as in the case of ⁇ -ray irradiation.
  • the surface layer having a biocompatible group can be bonded in a lateral direction parallel to the resin surface of the device substrate as compared with, for example, a method in which MPC is graft-polymerized directly to the resin surface of the device substrate.
  • Examples of the medical device include a medical device, an artificial organ, a cell culture container, and the like.
  • medical devices specifically, cell culture vessels, cell culture sheets, vials, plastic-coated vials, syringes, plastic-coated syringes, ampules, plastic-coated ampules, cartridges, bottles, plastic-coated bottles, pouches, pumps, sprayers, Stopper, plunger, cap, lid, needle, stent, catheter, implant, contact lens, microchannel chip, drug delivery system material, drain tube, artificial blood vessel, artificial organ, hemodialysis membrane, guard wire, blood filter, blood Examples include a storage pack, an endoscope, a biochip, a sugar chain synthesizing device, a molding auxiliary material, and a packaging material.
  • the medical device of the present invention is particularly preferably applied to catheters, artificial blood vessels, stents, and drain tubes.
  • catheters catheters, artificial blood vessels, stents, and drain tubes.
  • each member constituting the medical device of the present invention will be described.
  • the shape of the device substrate depends on the medical device targeted by the present invention.
  • the device substrate is not particularly limited as long as at least a part of the surface is made of a resin material.
  • the entire surface of the device substrate may be made of a resin material, or a part thereof may be made of a resin material. Further, the entire surface may be made of the same resin material, or may be made of a different resin material.
  • the material configuration of the device substrate is appropriately selected according to the design of the medical device.
  • the device substrate may have, for example, a configuration in which the whole is made of a single resin material, or may be a laminate in which a plurality of layers made of a resin material (hereinafter, “resin material layer”) are stacked. Further, a laminated body of a resin material layer and a layer made of an inorganic material, in which at least one surface layer is a resin material layer, may be used. Alternatively, a configuration in which an inorganic material and a resin material are mixed and at least a part of the surface is made of a resin material may be employed. Examples of the resin material layer included in the surface layer of these laminates include a hard coat layer provided to increase the hardness of the substrate surface.
  • the term “resin material” refers to a material containing 10% by mass or more of resin with respect to the entire material.
  • the resin material may be composed of, for example, a resin alone, or may be an organic-inorganic composite material containing the resin in the above range and mixing the resin and an inorganic substance.
  • the form of the resin material may be a solid body or a porous body. Further, in this specification, a resin is used in a concept including an elastomer.
  • polyolefin resin for example, polyolefin resin, epoxy resin, ene thiol resin, polyether resin, polyarylate resin, polysulfone resin, polyethersulfone resin, polyparaphenylene resin, polyarylene ether phosphine oxide resin, polyimide resin, Polyamide imide resin, acrylic resin, polyester resin, polyamide resin, polyurethane resin, polyurea resin, cellulose resin, silicone resin, fluororesin, polystyrene, polyvinyl chloride, polycarbonate resin, polyvinyl alcohol, ethylene-vinyl acetate copolymer (EVA) , Polysulfone, polyether nylon resin, polycycloolefin resin (COP) and the like.
  • the resin for example, polyolefin resin, epoxy resin, ene thiol resin, polyether resin, polyarylate resin, polysulfone resin, polyethersulfone resin, polyparaphenylene resin, polyarylene ether phosphine oxide
  • Polyolefin resins include polyethylene, polypropylene and the like.
  • the acrylic resin include poly (meth) acrylic acid, poly (meth) acrylate, polyacrylonitrile, polyacrylamide, and the like.
  • the polyester resin include polyethylene terephthalate and polyethylene naphthalate.
  • the cellulose resin include cellulose and cellulose acetate.
  • the fluororesin include polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), ethylene / tetrafluoroethylene copolymer (ETFE), and perfluoroalkoxy fluororesin (PFA).
  • Elastomers include thermosetting elastomers and thermoplastic elastomers.
  • thermosetting elastomer include isobutylene rubber, isoprene rubber, butadiene rubber, styrene / butadiene rubber (SBR), ethylene / propylene rubber (EPDM rubber), silicone rubber, urethane rubber, and fluorine rubber.
  • thermoplastic elastomer include styrene, olefin, vinyl chloride, polyester, polyurethane, and nylon.
  • the dry coating film is provided on the resin surface of the device substrate.
  • the dry coating film has a role of an adhesion layer for firmly fixing the surface layer on the resin surface of the device substrate. Therefore, the dry coating film is provided at least on the resin surface on which the surface layer is provided on the device substrate. That is, the area where the dry coating film and the surface layer are provided does not necessarily have to match. In the region where the surface layer is provided according to the design of the medical device, at least the region where the dry coating film is provided is set so that the surface layer does not directly contact the resin surface.
  • the constituent material of the dry coating film is mainly composed of metal oxide (D).
  • the metal oxide (D) is at least one selected from the group consisting of silicon oxide, titanium oxide and aluminum oxide, and is a simple substance of each metal oxide, a mixture of two or more kinds, or a group consisting of silicon, titanium and aluminum. It may be a composite oxide of two or more metals selected from the group consisting of:
  • an oxide of a metal represented by oxidation + metal name indicates an oxide having a stoichiometric composition ratio or a non-stoichiometric composition ratio unless otherwise specified.
  • the dry coating film may contain other components other than the metal oxide (D), if necessary, as long as the effects of the present invention are not impaired.
  • Other components include metal oxides other than the metal oxide (D), impurities in the material used for forming the dry coating film, and impurities mixed in forming the dry coating film.
  • the content of the other components contained in the dry coating film is within the above range not impairing the effects of the present invention, and is preferably 10% by mass or less, more preferably 5% by mass or less, and particularly preferably not contained.
  • the difference in the refractive index between the resin material used for the device substrate and the dry coating film is small in order to prevent reflection.
  • Other components may be included in the dry coating film within the above range for the purpose of adjusting the refractive index difference.
  • the dry coating film and the surface layer are bonded by a covalent bond.
  • the surface layer is typically formed by curing a composition containing a curable compound having a biocompatible group and a reactive group. During the curing, the reactive group of the curable compound reacts with the reactive group on the surface of the dry coating film to form a covalent bond. Therefore, the type of the metal oxide (D) is appropriately selected in combination with the reactive group of the curable compound used for forming the surface layer.
  • the metal oxide (D) is silicon oxide
  • the reactive group of the curable compound forming the surface layer is hydrolyzed because it is easy to produce and a strong covalent bond can be obtained.
  • Combinations that are reactive silyl groups are preferred.
  • a hydroxyl group is exposed on the surface of the metal oxide (D) and is used as a reactive group.
  • the silanol group (Si—OH) of the dry coating film and the silanol group generated by the hydrolysis reaction from the hydrolyzable silyl group undergo a dehydration condensation reaction to form a covalent bond by a siloxane bond (Si—O—Si). I do.
  • the method for forming the dry coating film is dry coating, and is not particularly limited as long as the method can firmly bond the metal oxide (D) to the resin surface of the device substrate without applying a large load to the device substrate.
  • a method such as a vacuum deposition method, a CVD method (thermal CVD method, a plasma CVD method, or an optical CVD method), a sputtering method, an ion beam sputtering method, and an ion assisted deposition (IAD: Ion Assisted Deposition) method can be given. .
  • the vacuum deposition method can be suitably used from the viewpoint of obtaining a high bonding strength while keeping the load on the device base material small and the simplicity of the apparatus.
  • Vacuum deposition can be subdivided into resistance heating, electron beam heating, high-frequency induction heating, reactive deposition, molecular beam epitaxy, hot wall deposition, ion plating, cluster ion beam, etc. Either method can be applied.
  • the material used for dry coating is appropriately selected according to the type of dry coating.
  • a deposition material containing a metal oxide (D) as a main component is used.
  • a vapor deposition material is heated and vaporized in a high vacuum, and the vaporized vapor deposition material is attached to the substrate surface to form a vapor deposition film.
  • a deposited film obtained by vacuum deposition can be treated as having the same composition as the used deposition material.
  • the shape of the vapor deposition material is not particularly limited, but may be a block shape, a plate shape, a thin plate shape (flake shape), a bead shape, a powder shape, or the like. Of these, it is preferable to process the powder into a pellet because the powder is easily scattered during vacuum deposition.
  • the method for producing the pellets is not limited, and for example, a method of compacting the powder into a pellet-shaped molded body may be mentioned.
  • the size of the pellet-shaped molded body is preferably, for example, 0.5 mm or more in diameter or major axis from the viewpoint of suppressing scattering during vacuum deposition.
  • the upper limit is not particularly limited, but is preferably about 1 to 3 cm in diameter or long diameter from the viewpoint of the size of the vapor deposition apparatus.
  • the size when the deposition material is made into a block shape, a plate shape, a flake shape, a bead shape, or the like can be the same as that in the case of the pellet-shaped molded body.
  • a normal method using a normal vacuum deposition apparatus can be applied without any particular limitation.
  • the device substrate is placed in an apparatus capable of reducing pressure, and a deposition material container filled with a deposition material is placed at a position facing the deposition film forming surface of the device substrate.
  • the size and shape of the evaporation material container are not particularly limited.
  • the material of the evaporation material container may be any material that does not react with the evaporation material and does not evaporate under the following vacuum evaporation conditions, and examples thereof include molybdenum, tungsten, and copper.
  • the heating of the deposition material is usually performed by heating the container material for the deposition material by an electron gun, a high-frequency induction heating method, or a resistance heating method.
  • the heating temperature of the container material for the deposition material is preferably from 1000 to 2000 ° C, more preferably from 1200 to 1800 ° C.
  • the temperature in the apparatus at the time of vacuum deposition is preferably appropriately selected from the range of 20 to 300 ° C. in consideration of the heat resistance of the device substrate to be used, and is appropriately selected from the range of 30 to 200 ° C. Is more preferred.
  • the temperature of the device substrate during vacuum deposition can be the same as the temperature in the apparatus during vacuum deposition. If the temperature of the device substrate at the time of vacuum deposition is 20 ° C. or higher, the film forming rate becomes good.
  • the upper limit of the temperature of the device substrate depends on the heat resistance of the constituent material of the device substrate.
  • the degree of vacuum before deposition in the apparatus during vacuum deposition is preferably 1 ⁇ 10 ⁇ 1 Pa or less, particularly preferably 1 ⁇ 10 ⁇ 2 Pa or less.
  • the distance between the deposition film forming surface of the device substrate and the deposition material is preferably 100 to 4000 mm, more preferably 200 to 2000 mm.
  • the vapor-deposited film can be formed on the inner peripheral surface of the tube by the above method.
  • a tube is formed by forming a vapor-deposited film on the main surface of the sheet-shaped device substrate and joining the end with the surface on which the vapor-deposited film is formed inside. And the like.
  • the surface layer may be formed on the vapor-deposited film and then formed into a tube shape, or the surface layer may be formed after being formed into a tube shape.
  • a dry coating film as a particularly dense film it is preferable to use a sputtering method or an ion-assisted evaporation method.
  • a specific method for forming a dry coating film by a sputtering method there is a method of selecting a sputtering target and an atmospheric gas according to a constituent material and performing sputtering by an ordinary method.
  • a target consisting of a simple substance of a metal selected from the group consisting of silicon, titanium and aluminum or a mixed metal target, and reacting in a sputtering gas having a sufficiently high oxidizing gas concentration
  • a film can be formed by performing sputtering.
  • a sputtering gas in this case, a mixed gas of argon and oxygen is preferably used.
  • a dry coating film made of a composite oxide may be obtained by using a plurality of types of targets made of a simple substance of silicon, titanium, or aluminum and adjusting the input power to each target. Also in this case, a dry coating film can be formed by performing reactive sputtering in a sputtering gas having a sufficiently high oxidizing gas concentration.
  • a metal target selected from the group consisting of silicon, titanium and aluminum
  • sputtering in an inert gas such as argon gas
  • the precursor layer may be formed by, for example, using a radio frequency (RF) plasma and reacting oxygen to form a dry coating film.
  • RF radio frequency
  • the target may be the metal oxide itself constituting the dry coating film.
  • a silicon carbide (SiC) target may be used as a target for obtaining a dry coating film made of silicon oxide by a sputtering method.
  • the thickness of the dry coating film is preferably from 1 to 200 nm, particularly preferably from 1 to 20 nm.
  • the thickness of the dry coating film is equal to or more than the lower limit of the above range, the effect of improving the substrate adhesion by the dry coating film is easily obtained sufficiently.
  • the thickness of the dry coating film is equal to or less than the upper limit of the above range, the durability of the dry coating film itself increases. Further, even when transparency is required in the obtained medical device, there is no problem in transparency as long as it is not more than the upper limit of the above range.
  • the method for measuring the thickness of the dry coating film is not particularly limited.
  • a method of observing a cross section of a silicon oxide layer with an electron microscope (SEM, TEM, etc.), a light interference film thickness meter, a spectroscopic ellipsometer, a step meter, or the like is used. There is a way.
  • the surface layer is a layer having a biocompatible group, which is provided on a dry coating film provided on the resin surface of the device substrate so as to be covalently bonded to the dry coating film.
  • the surface layer does not need to be provided in the entire region on the dry coating film, but is provided in an arrangement region according to the design of the medical device. In this way, the surface layer has sufficient durability because it is bonded via a covalent bond to the dry coating film firmly fixed on the resin surface of the device substrate.
  • the surface layer having a covalent bond with the dry coating film and having a biocompatible group includes a group capable of forming a covalent bond with the dry coating film containing metal oxide (D) as a main component, and a biocompatible group. And a surface layer composed of a cured product of a composition containing a compound having a group.
  • a group capable of forming a covalent bond with a dry coating film containing the metal oxide (D) as a main component of the compound a hydrolyzable silyl group is preferable, and an alkoxysilyl group is more preferable.
  • the amount of total organic carbon (TOC) eluted in water per unit area of 1 cm 2 of the surface layer Is preferably 10 mg / L or less.
  • the TOC elution amount is the mass [mg] of TOC eluted in water when the surface layer having an area of 1 cm 2 is immersed in 1 L of water at 40 ° C. for 7 days.
  • the TOC elution amount is preferably 10 mg / L or less, more preferably 5 mg / L or less, and more preferably 3 mg / L. The following are more preferred.
  • the TOC elution amount of the surface layer can be specifically measured as follows. After the surface layer is immersed in a predetermined amount of water at 40 ° C. for 7 days, the TOC concentration [mg / L] of the treated water is measured. The water used for immersion is distilled water or ion-exchanged water. The TOC elution amount [mg / L] is obtained by dividing the TOC concentration obtained above by the area of the immersed surface layer (unit: cm 2 ). The TOC concentration in water can be measured with a general TOC meter, for example, TNC-6000 (manufactured by Toray Engineering).
  • a sample of the surface layer used for measurement of the TOC elution amount a single surface layer obtained by forming a surface layer on a peelable substrate and peeling it off may be used, and the TOC under the above conditions (40 ° C., 7 days) may be used.
  • a substrate with a surface layer in which a surface layer is formed on a substrate having an elution amount of 0 [mg / L] may be used.
  • the biocompatible group in the surface layer includes a group represented by the following formula 1 (hereinafter, also referred to as “group 1”) and a group represented by the following formula 2 (hereinafter, also referred to as “group 2”).
  • group 3 a group represented by the following formula 3
  • group 4 a group represented by the following formula 4
  • n is an integer of 1 to 300.
  • R 1 to R 3 are each independently an alkyl group having 1 to 5 carbon atoms, and a is an integer of 1 to 5.
  • R 4 and R 5 are each independently an alkyl group having 1 to 5 carbon atoms, and X ⁇ is a group represented by the following formula 3-1 or a group represented by the following formula 3-2.
  • B is an integer of 1 to 5.
  • n is an integer of 1 to 300
  • R 6 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.
  • the alkyl group may be any of linear, branched and cyclic, and may be a combination thereof.
  • the group 1 (however, 50 to 100 mol% is the group 1 in the group 4) is referred to as “group 1 (4)”.
  • the biocompatible group contained in the surface layer may include any one of groups 1 (4), 2 and 3, or may include two or more of these.
  • Group 1 (4) is preferable as the biocompatible group.
  • the surface layer may have a bioaffinity group other than the group 1 (4), the group 2 and the group 3 as necessary, but preferably, the bioaffinity group of the surface layer is a group 1 (4), It consists of at least one member selected from the group consisting of groups 2 and 3.
  • the surface layer is formed of a group capable of forming a covalent bond with a dry coating film containing a metal oxide (D) as a main component, preferably a hydrolyzable silyl group, more preferably an alkoxysilyl group, and a biocompatible group.
  • the content of the biocompatible group in the solid content of the composition is preferably 25 to 83% by mass, and the content of the hydrolyzable silyl group is preferably 2 to 70% by mass.
  • the above compound is a compound having at least one biocompatible group selected from the group consisting of group 1 (4), group 2 and group 3 and an alkoxysilyl group (hereinafter, referred to as compound (X)).
  • compound (X) an alkoxysilyl group
  • the composition used for forming the surface layer contains the compound (X), the content of the biocompatible group in the solid content of the composition is 25 to 83% by mass, and the content of the alkoxysilyl group is 25 to 83% by mass. It is preferably a composition having a content of 2 to 70% by mass (hereinafter, referred to as composition (Y)).
  • composition (Y) will be described as an example of a composition for forming a surface layer, but the composition for forming a surface layer is not limited thereto as long as the obtained surface layer falls within the scope of the present invention.
  • the solid content in the composition refers to a residue obtained by removing the volatile component by vacuum drying the composition at 80 ° C. for 3 hours.
  • the cured product of the composition is a cured product of the solid content.
  • the “biocompatible group” is a biocompatible group composed of at least one selected from the group consisting of groups 1 (4), 2 and 3, unless otherwise specified.
  • the surface layer is made of a cured product of the composition (Y) containing the compound (X) means that the surface layer contains at least a cured product of a component containing the compound (X) that can be hydrolyzed and condensed.
  • the composition (Y) cures, the compound (X) has a silicyl group (Si—OH) due to a hydrolysis reaction due to having an alkoxysilyl group.
  • the silanol groups undergo a dehydration-condensation reaction to form a siloxane bond (Si—O—Si) to form a cured product.
  • composition (Y) contains a hydrolyzable silyl group-containing component other than the compound (X), preferably an alkoxysilyl group-containing component, the component and the compound (X) similarly form a siloxane bond. .
  • a silanol group generated by a hydrolysis reaction of the hydrolyzable silyl group-containing component in the composition (Y) containing the compound (X) is:
  • a covalent bond (glass material—O—Si) is formed by a dehydration condensation reaction with a hydroxyl group (glass material—OH) on the surface of the dry coating film.
  • the obtained surface layer has a sufficient amount of the biocompatible group, that is, has sufficient biocompatibility.
  • the content of the biocompatible group is 83% by mass or less, durability can be imparted to biocompatibility.
  • the content of the biocompatible group in the solid content in the composition (Y) is preferably from 30 to 83% by mass, and more preferably from 40 to 83% by mass.
  • the alkoxysilyl group when the content of the alkoxysilyl group is 2% by mass or more, when the composition (Y) is cured, the alkoxysilyl group forms a sufficient amount of covalent bond with the surface of the dry coating film.
  • the surface layer formed and obtained has excellent durability.
  • the content of the alkoxysilyl group is 70% by mass or less, a sufficient amount of a biocompatible group can be introduced.
  • the content of the alkoxysilyl group in the solid content in the composition (Y) is preferably from 2 to 40% by mass, and more preferably from 2 to 30% by mass.
  • Examples of the alkoxysilyl group of the compound (X) include a group represented by Formula 5. —Si (R 7 ) 3-t (OR 8 ) t Formula 5
  • R 7 is an alkyl group having 1 to 18 carbon atoms
  • R 8 is an alkyl group having 1 to 18 carbon atoms
  • t is an integer of 1 to 3.
  • R 7 and R 8 may be the same or different. It is preferable that they are the same from the viewpoint of manufacturing.
  • t is preferably 2 or more, and more preferably 3.
  • R 7 is preferably an alkyl group having 1 to 7 carbon atoms, more preferably a methyl group or an ethyl group.
  • R 8 is preferably an alkyl group having 1 to 6 carbon atoms, more preferably a methyl group or an ethyl group, from the viewpoint of the hydrolysis reaction rate and the volatility of by-products during the hydrolysis reaction.
  • the compound (X) for example, a compound (X1) having a polyoxyethylene chain as a main chain and having an alkoxysilyl group at a terminal or a side chain, which satisfies the requirements as the compound (X), an ethylenic double bond Compound (X2) having a polymerized hydrocarbon chain as a main chain and having a biocompatible group and an alkoxysilyl group in a side chain.
  • the compound (X1) may be, for example, a polyoxyethylene polyol or a polyoxyethylene polyol alkyl ether having at least one hydroxyl group (where the alkyl has 1 to 5 carbon atoms), and a hydroxyl group and a linkage of these compounds. It is obtained by introducing an alkoxysilyl group through a group.
  • the compound (X1) is, for example, a polyoxyalkylene polyol having a polyoxyethylene chain or a polyoxyalkylene polyol alkyl ether having a polyoxyethylene chain and having at least one hydroxyl group (provided that the number of carbon atoms of the alkyl is Is 1 to 5.) and a silane compound having a hydroxyl-reactive group and an alkoxysilyl group (hereinafter, also referred to as silane compound (S)) at a predetermined ratio.
  • silane compound (S) silane compound having a hydroxyl-reactive group and an alkoxysilyl group
  • the compound (X1) is obtained by adding an alkoxysilyl group to a polyoxyethylene polyol or a polyoxyethylene polyol alkyl ether having at least one hydroxyl group (where the alkyl group has 1 to 5 carbon atoms).
  • the predetermined group include the same groups as to Q 1 in the formula (X11) to be described later.
  • Examples of the polyoxyalkylene polyol to be used include compounds obtained by ring-opening addition polymerization of an alkylene monoepoxide containing at least ethylene oxide to a relatively low-molecular-weight polyol such as an alkane polyol, an etheric oxygen atom-containing polyol, or a sugar alcohol.
  • Examples of the oxyalkylene group in the polyoxyalkylene polyol include an oxyethylene group, an oxypropylene group, an oxy1,2-butylene group, an oxy2,3-butylene group, and an oxyisobutylene group.
  • polyoxyalkylene polyol alkyl ether examples include compounds in which a part of the hydroxyl group of such a polyoxyalkylene polyol is ether-bonded to an aliphatic alcohol having 1 to 5 carbon atoms.
  • polyoxyalkylene polyol alkyl ether means a polyoxyalkylene polyol alkyl ether having at least one hydroxyl group (provided that the alkyl has 1 to 5 carbon atoms), unless otherwise specified. . The same applies when “oxyalkylene” is changed to “oxyethylene”.
  • the oxyalkylene group contained in the polyoxyalkylene polyol and the polyoxyalkylene polyol alkyl ether may be composed of only an oxyethylene group, or may be composed of a combination of an oxyethylene group and another oxyalkylene group.
  • Polyoxyethylene polyol or polyoxyethylene polyol alkyl ether having only an oxyethylene group is preferable from the viewpoint of easy molecular design as the compound (X1).
  • the polyoxyethylene polyol and the polyoxyethylene polyol alkyl ether may be collectively referred to as a polyoxyethylene polyol or the like.
  • the compound (X1) is preferably a reaction product of a polyoxyethylene polyol or the like and a silane compound (S).
  • the number of hydroxyl groups in polyoxyethylene polyol and the like is from 1 to 6, preferably from 1 to 4, and particularly preferably from 1 to 3, from the viewpoint of ease of molecular design as compound (X1).
  • polyoxyethylene polyols specifically, polyoxyethylene glycol, polyoxyethylene glyceryl ether, trimethylolpropane trioxyethylene ether, pentaerythritol polyoxyethylene ether, dipentaerythritol polyoxyethylene ether, polyoxyethylene glycol Monoalkyl ethers (where the alkyl has 1 to 5 carbon atoms) and the like.
  • the compound (X1) is represented by the following formula and the polyoxyethylene glycol and R 9 -Q 11 -Si (R 7 ) 3- t (OR 8 )
  • the compound (X11) represented by the symbol (X11) in the formula, which is obtained by reacting the silane compound (S1) represented by t is exemplified.
  • n1 in polyoxyethylene glycol is an integer of 1 to 300, preferably 2 to 100, more preferably 4 to 20.
  • R 7 , R 8 and t in the silane compound (S1) are the same as in the case of the above formula 5, including preferred embodiments.
  • R 9 in the silane compound (S1) is a group reactive with a hydroxyl group, and includes a hydroxyl group, a carboxyl group, an isocyanate group, and an epoxy group.
  • Q 11 may have an etheric oxygen atom between carbon atoms having 2 to 20 carbon atoms, and a hydrogen atom is substituted by a halogen atom such as a chlorine atom or a fluorine atom or a hydroxyl group. Is a divalent hydrocarbon group. When a hydrogen atom is substituted with a hydroxyl group, the number of substituted hydroxyl groups is preferably 1 to 5.
  • Q 1 is a residue in which R 9 -Q 11 of the silane compound (S1) has reacted with a hydroxyl group of polyoxyethylene glycol, and R 9 ′ -Q 11 (the side bonded to O is R 9 a ', can be shown in the side that bind to alkoxysilyl group is Q 11.).
  • -CH 2 OC 3 H 6- , -CF 2 OC 3 H 6- and the like are more preferable.
  • -CONHC 3 H 6 -, - CONHC 2 H 4 -, - CH 2 OC 3 H 6 -, - CF 2 OC 3 H 6 -, - C 2 H 4 -, - C 3 H 6 - , and -C 2 F 4 - more preferably any one selected from, -CONHC 3 H 6 -, - CONHC 2 H 4 -, - C 2 H 4 -, - C 3 H 6 - are particularly preferred.
  • the compound (X11) may be obtained by reacting polyoxyethylene glycol with allyl chloride under basic conditions and then modifying the silane by a hydrosilylation reaction.
  • the ratio of the group 1 in the compound (X11) to the group 1 in the group 4 is 100 mol%. That is, group 1 in the compound (X11) are all as defined above is a group 1 contained in the base 4, the oxyethylene chains in the compound (X1), the proportion one terminal is R 6 is not less than half, In the oxyethylene chain in the compound (X11), one end is all R 6 (in this case, a hydrogen atom).
  • the content of the biocompatible group in the compound (X11) is the mass% of n1 (OCH 2 CH 2 ) —O in the formula (X11), and the content of the alkoxysilyl group is-in the formula (X11). Si (R 7 ) 3 -t (OR 8 ) The mass% of t .
  • the content of the biocompatible group and the alkoxysilyl group in the compound (X11) is appropriately adjusted according to the solid composition of the composition (Y).
  • the content of the biocompatible group in the compound (X11) is, for example, preferably 10 to 90% by mass, more preferably 25 to 83% by mass, still more preferably 40 to 83% by mass, and particularly preferably 60 to 83% by mass.
  • the content of the alkoxysilyl group in the compound (X11) is preferably 1 to 70% by mass, more preferably 2 to 70% by mass, further preferably 2 to 45% by mass, and particularly preferably 10 to 30% by mass.
  • the terminal hydrogen atom of the compound (X11) is a compound substituted for R 6 other than hydrogen atom can also be used as the compound (X1). That is, in the above reaction formula, a compound obtained by using a polyoxyethylene glycol monoalkyl ether (alkyl is R 6 ) instead of the polyoxyethylene glycol having 2 hydroxyl groups can also be used as the compound (X1). .
  • R 6 is preferably a methyl group or an ethyl group, and more preferably a methyl group.
  • the polyoxyethylene polyol is a polyoxyethylene glyceryl ether having 3 hydroxyl groups
  • the polyoxyethylene glyceryl ether and R 9 -Q 11 -Si (R 7 ) 3 are represented by the following formula.
  • -T (OR 8 ) A compound (X12) represented by the symbol (X12) obtained by reacting the silane compound (S1) represented by t is exemplified.
  • n1 in polyoxyethylene glyceryl ether can be the same as n1 in polyoxyethylene glycol, including preferred embodiments.
  • the silane compound (S1) can be the same as described above.
  • Q 1 may be similarly including preferred embodiments and Q 1 in the compound (X11).
  • the ratio of the group 1 in the compound (X12) to the group 1 in the group 4 is 67 mol%.
  • the content of the biocompatible group in the compound (X12) is the total mass% of O— (CH 2 CH 2 O) n1 — and O— (CH 2 CH 2 O) n1 —H in the formula (X12). It is adjusted to 25 to 83% by mass.
  • the content of the biocompatible group and the content of the alkoxysilyl group in the compound (X12) can be the same as that of the compound (X11), including a preferable range.
  • R 6 is preferably a methyl group.
  • the content of the structure other than the biocompatible group and the alkoxysilyl group is preferably from 10 to 50% by mass, and more preferably from 20 to 30% by mass, from the viewpoint of compatibility between the biocompatibility in the surface layer and the durability thereof. Is more preferred.
  • the weight average molecular weight (hereinafter, sometimes referred to as “Mw”) of the compound (X1) is preferably from 100 to 10,000, more preferably from 500 to 2,000, from the viewpoint of easy availability of raw materials. Mw of compound (X1) is calculated by size exclusion chromatography.
  • the compound (X1) has been described above using polyoxyethylene glycol and polyoxyethylene glyceryl ether as examples of polyoxyethylene polyol and the like. Similarly, for other polyoxyethylene polyols and the like, the ratio of group 1 to group 1 in group 4, the content of biocompatible groups, the content of alkoxysilyl groups, and the like are appropriately adjusted to desired ratios. And compound (X1).
  • Compound (X1) may be a partially hydrolyzed condensate thereof.
  • the degree of condensation is appropriately adjusted so that the viscosity does not hinder the formation of the surface layer on the surface of the dry coating film as described below.
  • the Mw of the partially hydrolyzed condensate is preferably from 1,000 to 1,000,000, and more preferably from 1,000 to 100,000. The preferred range of Mw is the same for the following partially hydrolyzed cocondensates.
  • the content (% by mass) of the alkoxysilyl group in the partially hydrolyzed condensate is treated as being equivalent to the content (% by mass) of the alkoxysilyl group of the raw material silane compound.
  • the content (% by mass) of the alkoxysilyl group can be calculated from the mixing ratio of the raw material silane compound.
  • the compound (X1) may be a partially hydrolyzed cocondensate obtained by partially hydrolyzing and cocondensing two or more compounds (X1) so as to contain a biocompatible group and an alkoxysilyl group at a desired ratio.
  • the compound (X1) may be obtained by converting an alkoxysilane compound having no biocompatible group with the compound (X1) into a partially hydrolyzed condensate obtained at a desired ratio as the compound (X). May be a partially hydrolyzed co-condensate obtained by partially hydrolyzing and co-condensing.
  • alkoxysilane compound having no biocompatible group examples include an alkoxysilane compound of the following formula 6 (hereinafter, also referred to as compound 6). Si (R 20 ) 4-p (OR 21 ) p formula 6
  • R 20 is a monovalent organic group having no polyoxyethylene chain
  • R 21 is an alkyl group having 1 to 18 carbon atoms
  • p is an integer of 1 to 4.
  • each of R 20 and R 21 may be the same or different. It is preferable that they are the same from the viewpoint of manufacturing.
  • R 20 include an alkyl group having 1 to 18 carbon atoms, and a methyl group is preferable from the viewpoint of steric hindrance during the condensation reaction.
  • R 21 is preferably an alkyl group having 1 to 6 carbon atoms, more preferably a methyl group or an ethyl group.
  • the compound (X2) for example, a (meth) acrylate having a biocompatible group and a (meth) acrylate having an alkoxysilyl group are indispensable.
  • a polymerized (meth) acrylate copolymer is exemplified.
  • the raw material monomer contains each of the above (meth) acrylates so that the obtained (meth) acrylate copolymer contains a biocompatible group and an alkoxysilyl group at a desired ratio as the compound (X). Adjust the volume.
  • Examples of the (meth) acrylate copolymer include a copolymer (X21) represented by the following formula (X21).
  • R 1 to R 6 , X ⁇ and a and b are the same as in the formulas 1 to 4.
  • R 1 to R 3 are independently preferably a methyl group
  • R 4 and R 5 are independently preferably a methyl group.
  • R 6 is preferably a methyl group or a hydrogen atom.
  • a and b are preferably each independently 2.
  • n2 is an integer of 1 to 300, preferably 1 to 100, more preferably 1 to 20.
  • R 7 , R 8 and t are the same as in the case of the above formula 5, including preferred embodiments.
  • R in each unit is independently a hydrogen atom or a methyl group.
  • R 10 is a hydrogen atom or a monovalent organic group having no biocompatible group and no alkoxysilyl group.
  • R 10 is preferably a hydrogen atom or an alkyl group having 1 to 100 carbon atoms, and more preferably an alkyl group having 1 to 20 carbon atoms.
  • the copolymer (X21) may be a random copolymer or a block copolymer.
  • Q 2 , Q 4 and Q 5 each have 2 to 10 carbon atoms, may have an etheric oxygen atom between carbon atoms, and the hydrogen atom may be a halogen atom such as a chlorine atom or a fluorine atom; It is a divalent hydrocarbon group which may be substituted by a hydroxyl group.
  • Q 2 is, -C 2 H 4 -, - C 3 H 6 -, - C 4 H 8 - are preferred, -C 3 H 6 -, - C 4 H 8 - are more preferable, and -C 3 H 6 -Is preferred.
  • Q 4 and Q 5 are preferably each independently —C 2 H 4 —, —C 3 H 6 —, or —C 4 H 8 —, more preferably —C 2 H 4 — or —C 3 H 6 —.
  • -C 2 H 4 - is more preferable.
  • Q 3 is a single bond or —OQ 6 —, preferably a single bond.
  • Q 6 is the same as that of Q 2.
  • e represents the number of units having an alkoxysilyl group (hereinafter referred to as unit (A)) when the total number of units of the copolymer is 100.
  • the number is shown when the total unit number of the united unit is set to 100.
  • the content of the biocompatible group and the alkoxysilyl group (—Si (R 7 ) 3-t (OR 8 ) t ) in the copolymer (X21) can be adjusted.
  • the ratio of e to i in the copolymer (X21) is appropriately adjusted according to the solid content composition of the composition (Y).
  • the content of the biocompatible group in the copolymer (X21) is, for example, preferably 20 to 90% by mass, more preferably 25 to 83% by mass, still more preferably 30 to 83% by mass, and more preferably 40 to 83% by mass. Particularly preferred.
  • the content of the alkoxysilyl group in the copolymer (X21) is preferably 1 to 70% by mass, more preferably 2 to 70% by mass, further preferably 2 to 25% by mass, and particularly preferably 2 to 15% by mass.
  • the copolymer (X21) a copolymer composed of only the unit (A) and the unit (B1) is preferable.
  • the (meth) acrylate as a raw material of the unit (A), the unit (B1), the unit (B2), the unit (B3), and the unit (C) will be referred to as (meth) acrylate (A) and (meth) acrylate ( B1), (meth) acrylate (B2), (meth) acrylate (B3), and (meth) acrylate (C).
  • (meth) acrylate (B1), (meth) acrylate (B2) and (meth) acrylate (B3) are collectively referred to as (meth) acrylate (B).
  • (meth) acrylate (B) the meanings of the symbols are all the same as in the copolymer (X21).
  • (Meth) acrylate (A) is CH 2 CRCR—COO—Q 2 —Si (R 7 ) 3-t (OR 8 ) t , and CH 2 CRCR—COO—Q 2 —Si (OR 8 ) 3 is preferable, and CH 2 CRCR—COO— (CH 2 ) 3 —Si (OCH 3 ) 3 and CH 2 CRCR—COO— (CH 2 ) 3 —Si (OC 2 H 5 ) 3 are particularly preferable.
  • n2 is more preferably 1 to 20.
  • the (meth) acrylate (B2) is CH 2 CRCR—COO—Q 4 — (PO 4 — ) — (CH 2 ) a —N + R 1 R 2 R 3 and CH 2 2CR—COO— ( CH 2 ) 2 — (PO 4 ⁇ ) — (CH 2 ) 2 —N + (CH 3 ) 3 is preferred.
  • the (meth) acrylate (C) has CH 2 CRCR—COO—R 10 and includes methyl methacrylate, butyl methacrylate, dodecyl methacrylate and the like.
  • the copolymer (X21) is prepared, for example, by preparing a raw material (meth) acrylate so that e to i are in the above-mentioned predetermined ratio, and in the presence of a polymerization initiator, conventionally known solution polymerization, bulk polymerization, suspension polymerization, and the like. It can be obtained by copolymerization by a method such as suspension polymerization or emulsion polymerization.
  • the content of the structure other than the biocompatible group and the alkoxysilyl group is preferably from 15 to 55% by mass, and more preferably from 15 to 40% by mass, from the viewpoint of compatibility between the biocompatibility in the surface layer and its durability. % Is more preferred.
  • Mw of the compound (X2) is preferably from 1,000 to 1,000,000, and more preferably from 20,000 to 100,000, from the viewpoint of ease of production. Mw of the compound (X2) is calculated by size exclusion chromatography.
  • Compound (X2) may be a partially hydrolyzed condensate thereof.
  • the degree of condensation is appropriately adjusted so that the viscosity does not hinder the formation of the surface layer on the surface of the dry coating film as described later.
  • the Mw of the partially hydrolyzed condensate is preferably from 2,000 to 2,000,000, and more preferably from 30,000 to 300,000. The preferred range of Mw is the same for the following partially hydrolyzed condensates.
  • the compound (X2) may be a partially hydrolyzed cocondensate obtained by partially hydrolyzing and cocondensing two or more compounds (X2) so as to contain a biocompatible group and an alkoxysilyl group at a desired ratio.
  • the compound (X2) may be obtained by converting an alkoxysilane compound having no biocompatible group with the compound (X2) into a partially hydrolyzed condensate obtained at a desired ratio as the compound (X). May be a partially hydrolyzed co-condensate obtained by partially hydrolyzing and co-condensing.
  • the composition (Y) may contain one type of the compound (X) alone or may contain two or more types of the compound (X). When two or more compounds (X) are used, it is preferable that two or more compounds (X1) alone or two or more compounds (X2) alone be used.
  • the solid content of the composition (Y) is composed of only the compound (X)
  • the compound (X) has a biocompatible group content and an alkoxysilyl group content within the above-mentioned predetermined ranges. To be selected.
  • the proportion of the compound (X) in the solid content in the composition (Y) is, for example, preferably from 25 to 100% by mass, more preferably from 50 to 100% by mass, and still more preferably from 75 to 100% by mass.
  • the composition (Y) may contain other components other than the compound (X).
  • Other components include other solid components other than the compound (X) contained in the surface layer as solid components.
  • the composition (Y) contains only a solid content.
  • the surface layer is formed by wet coating, it further contains, as other components, a liquid medium which is removed at the time of forming the surface layer.
  • the other solid components may be components that cure similarly to compound (X), or may be non-curable components.
  • examples of other solid components include impurities, functional additives, catalysts, and the like, among the raw materials and by-products used in the production process of the compound (X), which could not be completely removed.
  • the functional additive include an ultraviolet absorber, a light stabilizer, an antioxidant, and a leveling agent.
  • the other solid content is such that the obtained surface layer can satisfy the above-mentioned TOC elution amount range.
  • a component capable of being hydrolyzed and condensed with the compound (X) is preferable, and a hydrolyzable silyl group-containing component other than the compound (X), and further an alkoxysilyl group-containing component is more preferable.
  • the composition (Y) does not contain a solid content other than the compound (X).
  • the compound (X) contains a biocompatible group at a ratio of 25 to 83% by mass and an alkoxysilyl group at 2 to 70% by mass. %.
  • the catalyst a conventionally known catalyst used for a hydrolysis-condensation reaction of an alkoxysilyl group is used without any particular limitation.
  • the catalyst include acids such as hydrochloric acid, nitric acid, acetic acid, sulfuric acid, phosphoric acid, and sulfonic acid such as methanesulfonic acid and p-toluenesulfonic acid; bases such as sodium hydroxide, potassium hydroxide, and ammonia; And titanium-based metal catalysts.
  • an alkoxysilane compound having no biocompatible group and / or a partial hydrolyzed condensate thereof may be used as other solid components.
  • the alkoxysilane compound having no biocompatible group the above compound 6 is preferable.
  • an alkoxysilane compound having no biocompatible group is used as a partially hydrolyzed condensate, its Mw is preferably from 100 to 100,000, more preferably from 100 to 10,000.
  • the composition (Y) contains the compound (X1) as a solid content and an alkoxysilane compound having no biocompatible group, the total of the compound (X1) and the alkoxysilane compound not having a biocompatible group,
  • the content of the biocompatible group is preferably 25 to 83% by mass, and the content of the alkoxysilyl group is preferably 2 to 70% by mass. That is, it is preferable not to contain a compound having a biocompatible group and / or an alkoxysilyl group other than these as a solid content.
  • the ratio of the alkoxysilane compound having no biocompatible group to 100 parts by mass of the compound (X1) is preferably 50 to 200 parts by mass, more preferably 50 to 100 parts by mass.
  • the total content of the compound (X1), the alkoxysilane compound having no biocompatible group and the other solid components other than the catalyst in the total solid content is a total. Is preferably 40% by mass or less, more preferably 20% by mass or less, and most preferably not contained.
  • an alkoxysilane compound other than the compound (X2) may be used as necessary.
  • the content of the compound (X2) and other solid components other than the catalyst in the total solid content is preferably 40% by mass or less in total, and 20% by mass or less. The following are more preferable, and it is most preferable not to contain.
  • the liquid medium contained in the composition (Y) may be any liquid medium capable of uniformly dissolving or dispersing a solid content containing the compound (X). Can be selected as appropriate. Since the liquid medium must be finally removed at the time of forming the surface layer, its boiling point is preferably in the range of 60 to 160 ° C., more preferably in the range of 60 to 120 ° C.
  • liquid medium examples include alcohols, ethers, ketones, and acetates.
  • liquid medium satisfying the above boiling point conditions include isopropyl alcohol (IPA), ethanol, propylene glycol monomethyl ether, and 2-butanone. These may be used alone or in combination of two or more.
  • the liquid medium can contain water for hydrolyzing the hydrolyzable silyl group-containing component containing the compound (X), but preferably does not contain water from the viewpoint of storage stability. However, even when the liquid medium does not contain water, the hydrolyzable silyl group-containing component containing the compound (X) can undergo a hydrolysis reaction with atmospheric moisture, so that the water content in the liquid medium is not essential. .
  • the solid content concentration is preferably 0.1 to 50% by mass, more preferably 1 to 30% by mass, and still more preferably 1 to 15% by mass.
  • the film thickness of the surface layer formed by wet coating using the composition (Y) tends to be within a suitable range in which the anti-algal properties and the durability can be sufficiently exhibited.
  • the solid content concentration of the composition (Y) can be calculated from the mass of the composition (Y) after vacuum drying at 80 ° C. for 3 hours and the mass of the composition (Y) before heating. It may be calculated from the total solid content and the amount of the liquid medium mixed at the time of production of the composition (Y).
  • composition (Y) containing a liquid medium preferably contains the liquid medium in an amount of 50 to 99.5% by mass, more preferably 65 to 99% by mass, and even more preferably 70 to 99% by mass. .
  • the method for producing the composition (Y) is not particularly limited.
  • the composition contains a solid containing the compound (X) and further contains a liquid medium, these solids and the liquid medium may be mixed so as to have the above-mentioned content.
  • the composition (Y) contains the compound (X), the content of the biocompatible group in the solid content is 25 to 83% by mass, and the content of the alkoxysilyl group is Since the content is 2 to 70% by mass, the surface layer composed of a cured product of the composition formed on the surface of the dry coating film using the composition (Y) has excellent biocompatibility and durability of biocompatibility Excellent.
  • the thickness of the surface layer is preferably 0.5 to 20 nm, particularly preferably 0.5 to 10 nm. When the thickness of the surface layer is equal to or more than the lower limit of the above range, biocompatibility and durability thereof are easily exhibited. When the thickness of the surface layer is equal to or less than the upper limit of the above range, the strength is excellent.
  • the thickness of the surface layer is determined by measurement with an X-ray reflectometer such as ATX-G manufactured by Rigaku Corporation.
  • a dry coating or a wet coating is mentioned, and a dry coating is preferable.
  • Examples of the dry coating include methods such as vacuum deposition, CVD, and sputtering.
  • the vacuum evaporation method can be suitably used. Vacuum deposition can be subdivided into resistance heating, electron beam heating, high frequency induction heating, reactive deposition, molecular beam epitaxy, hot wall deposition, ion plating, cluster ion beam, etc. Either method can be applied. From the viewpoint of suppressing the decomposition of the compound (X) and the simplicity of the apparatus, the resistance heating method can be suitably used.
  • the vacuum evaporation apparatus is not particularly limited, and a known apparatus can be used.
  • the film formation conditions in the case of using the vacuum evaporation method vary depending on the type of the vacuum evaporation method to be applied.
  • the degree of vacuum before evaporation is preferably 1 ⁇ 10 ⁇ 2 Pa or less, and 1 ⁇ 10 ⁇ 3 Pa The following are particularly preferred.
  • the heating temperature of the deposition material is not particularly limited as long as the deposition material has a sufficient vapor pressure. Specifically, the temperature is preferably from 30 to 400 ° C, particularly preferably from 50 to 300 ° C.
  • the film forming rate is improved.
  • the amount is equal to or less than the upper limit of the above range, the surface layer can be formed in a predetermined region on the dry coating film without decomposition of the compound (X).
  • the temperature of the device substrate with a dry coating film during vacuum deposition depends on the heat resistance of the constituent materials of the device substrate, but is preferably in the range of 20 to 200 ° C.
  • the film forming rate becomes good. If the temperature of the device substrate with a dry coating film is 200 ° C or less, a film can be formed on the surface of the dry coating film without condensation reaction, and it can be covalently bonded to the surface of the dry coating film immediately after film formation. is there.
  • the upper limit of the temperature of the device substrate with a dry coating film is more preferably 100 ° C. The upper limit of the temperature of the device substrate with the dry coating film is adjusted in consideration of the heat resistance of the constituent material of the device substrate in addition to the above.
  • the composition (Y) is adhered to a predetermined region on the upper surface of the dry coating film, and the thickness of the compound (X) is 0.5 wt. It is preferable to carry out the treatment so as to be 10 mg / m 2 .
  • Adhesion amount of the compound (X) is more preferably 0.5 ⁇ 5mg / m 2, particularly preferably 1.0 ⁇ 5.0mg / m 2.
  • the reaction of the compound (X) proceeds almost simultaneously by adjusting the temperature of the dry coating film during the film formation as described above.
  • a part of the silanol group generated by the hydrolysis reaction from the alkoxysilyl group of the compound (X) is subjected to a condensation reaction, whereby the molecules are bonded.
  • the silanol group generated from the compound (X) undergoes a condensation reaction with a metal-OH group derived from the metal oxide (D) on the surface of the dry coating film, and the dry coating film and the surface layer are joined by a covalent bond.
  • a composition (Y) containing the liquid medium described above is applied to a predetermined surface of a dry coating film to obtain a coating film (hereinafter, also referred to as an “application step”). ) And curing the coating film to obtain a surface layer (hereinafter, also referred to as “curing step”).
  • Examples of a method for applying the composition (Y) to the surface of the dry coating film in the application step include a dip coating method, a spin coating method, a wipe coating method, a spray coating method, a squeegee coating method, a die coating method, an ink jet method, and a flow coating method. Method, roll coating method, casting method, Langmuir-Blodgett method, gravure coating method and the like.
  • heating is preferred as a method for curing the coating film.
  • the heating temperature depends on the type of compound (X), but is preferably from 50 to 200 ° C, more preferably from 80 to 150 ° C.
  • the heating temperature is preferably a temperature equal to or higher than the boiling point of the liquid medium.
  • a process other than the application step and the drying step may be performed as necessary.
  • a treatment such as humidification may be performed simultaneously with the curing step, or before or after the curing step.
  • the excess compound which is a compound in the surface layer, may be removed as necessary.
  • a specific method for example, a method in which a solvent, for example, a compound used as a liquid medium of the composition (Y), is poured onto the surface layer, or a solvent, for example, a compound used as a liquid medium of the composition (Y) is impregnated. Wiping with a cloth.
  • the medical device of the present invention is a medical device having a biocompatible surface layer on a resin surface of a device substrate using a resin material.
  • Compound (X11-1) Compound (X11-1) having the following structure, that is, 2- [methoxy (polyethyleneoxy) 9-12 propyl] trimethoxysilane, commercially available product, SIM6492.92 (trade name, Gelest) Was prepared.
  • Compound (X11-1) the terminal hydrogen atom of the compound (X11) is replaced with a methyl group, n1 is 9 ⁇ 12, Q 1 is -C 3 H 6 -, t is 3, the compound of R 8 is a methyl group It is.
  • Compound (X11-2) Compound (X11-2) having the same molecular structure as compound (X11-1) except that the number of repeating oxyethylene groups is 6 to 9, that is, 2- [methoxy (polyethyleneoxy) 6 As [-9 propyl] trimethoxysilane, a commercially available product, SIM6492.7 (trade name, manufactured by Gelest) was prepared.
  • reaction mixture was heated under reduced pressure by a rotary evaporator to remove triethylamine, thereby obtaining a compound (X12-1) as a colorless transparent liquid.
  • the yield was 327 g, and the yield was 100%.
  • Example 1 A 3 mm-thick polystyrene film (manufactured by Mitsubishi Plastics) cut into a length of 108 mm and a width of 75 mm was used as a device substrate. Using an AGC ceramics SiC target (trade name SC), 40% by volume of oxygen gas was mixed and introduced into the entire surface of one main surface of the polystyrene film at a pressure of 0.5 Pa, a frequency of 100 kHz, and a pressure of 0.5 Pa.
  • AGC ceramics SiC target trade name SC
  • Pulse sputtering with a power density of 3.25 w / cm 2 and a reversal pulse width of 4.5 ⁇ sec was performed to form a 10-nm-thick dry coating film of silicon oxide on the main surface of the polystyrene film.
  • the polystyrene film with the dry coating film is washed, and the compound (X11-1) is vacuum-deposited on the surface on which the dry coating film is formed (vacuum degree before deposition; 3.4 ⁇ 10 ⁇ 4 Pa, polystyrene with the dry coating film)
  • the temperature of the film was 25 ° C. and the temperature of the compound (X11-1) was 60 ° C.) to form a surface layer having a thickness of 2 nm. In this way, a medical device 1 in which a dry coating film and a surface layer were sequentially formed on a polystyrene film was obtained.
  • Example 2 Medical device 2 was obtained in the same manner as in Example 1, except that compound (X11-2) was used instead of compound (X11-1).
  • Example 3 A solution containing the copolymer (X21-1) (solid content concentration: 30% by mass) is mixed with 1-methoxy-2-propanol, diacetone alcohol and a 0.1% by mass aqueous solution of nitric acid at a mass ratio of 51: 9: 40. The solvent was added to the solvent so as to have a solid concentration of 10% by mass, and stirred at 50 ° C. for 16 hours to obtain a liquid composition containing a partially hydrolyzed condensate of the copolymer (X21-1). Table 2 shows Mw of the obtained partially hydrolyzed condensate.
  • this liquid composition was dissolved in a mixed solvent of methoxypropanol and diacetone alcohol in a ratio of 85:15 (mass ratio) so as to have a solid content concentration of 1.0% by mass to obtain a surface layer forming composition. .
  • the polystyrene film with a dry coating film prepared in the same manner as in Example 1 was washed, and a coating film of the composition for forming a surface layer was formed on the surface on which the dry coating film was formed by dip coating using the composition for forming a surface layer. Formed. Next, this was dried in a hot air circulating oven at 50 ° C. for 1 hour to form a 1.8 nm-thick surface layer. Thus, a medical device 3 in which a dry coating film and a surface layer were sequentially formed on a polystyrene film was obtained.
  • Examples 4, 5, 6 In the same manner as in Example 3, except that the copolymer (X21-1) was changed to a copolymer (X21-2), a copolymer (X21-3) or a compound (X12-1), Medical devices 4, 5, and 6 were obtained from a polystyrene film with a coating film.
  • Table 2 or Table 1 shows Mw of the copolymer (X21-2), the copolymer (X21-3), or the partially hydrolyzed condensate of the compound (X12-1).
  • Example 7 to 12 Medical devices 7 to 12 having a surface layer directly formed on a polystyrene film were obtained in the same manner as in Examples 1 to 6 except that a polystyrene film was used instead of the polystyrene film with a dry coating film.
  • Example 13 and 14 The homopolymer (M) was dissolved in a mixed solvent of methoxypropanol and diacetone alcohol in a ratio of 85:15 (mass ratio) so as to have a solid content concentration of 1.0% by mass to obtain a composition for forming a surface layer.
  • a medical device 13 was obtained from a polystyrene film with a dry coating film in the same manner as in Example 3.
  • a medical device 14 having a surface layer directly formed on a polystyrene film was obtained in the same manner as described above except that a polystyrene film was used instead of the polystyrene film with a dry coating film.
  • Example 15 and 16 In the same manner as in Example 3, except that the copolymer (X21-1) was changed to the compound (Cf1), a medical device 15 was obtained from a polystyrene film provided with a dry coating film. Further, a medical device 16 having a surface layer directly formed on a polystyrene film was obtained in the same manner as described above except that a polystyrene film was used instead of the polystyrene film with a dry coating film. Table 1 shows the Mw of the partially hydrolyzed condensate of the compound (Cf1).
  • Example 17 As the medical device 17, a polystyrene film with a dry coating film was used as it was. In Example 18, a polystyrene film was used as the medical device 18 as it was.
  • a cell suspension was prepared using MEM supplemented with 10% FBS as a medium so that the TIG-3 cells, which were confirmed to have a cell survival rate of 97% or more at the time of seeding, became 130,000 cells per 3 mL.
  • the cells were inoculated by dispensing 3 mL of the cell suspension into a petri dish provided with the above-described evaluation substrate, and cultured in a 37 ° C. incubator for 24 hours. Thereafter, the observation area was set to a range of 1.8 mm ⁇ 1.3 mm, and microscopic observation (10 times) was performed in three observation areas, and adhesion was judged based on the presence or absence of cell expansion based on the following criteria.
  • the state in which the cells spread in an elliptical or circular shape with respect to the substrate is defined as cell extension.
  • Example 17 was evaluated on the dry coating film surface.
  • Example 18 evaluated the surface of a polystyrene film.
  • ⁇ No cells adhered to all observation areas. “ ⁇ ”: Cells are attached to a part of at least one observation region. “X”; cells adhere to almost the entire observation area at all locations.
  • Example 19 to 36 The medical devices 19 of Examples 19 to 36 were prepared in the same manner as in Examples 1 to 18 except that a 125 ⁇ m-thick COP film (manufactured by Zeon Corporation) cut into 108 mm long and 75 mm wide was used as the device substrate. ⁇ 36 were obtained. The obtained medical devices 19 to 36 were evaluated in the same manner as above. Table 4 shows the results.

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Vascular Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Materials Engineering (AREA)
  • Composite Materials (AREA)
  • Inorganic Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Ceramic Engineering (AREA)
  • Materials For Medical Uses (AREA)
  • Laminated Bodies (AREA)

Abstract

L'invention concerne un dispositif médical comprenant un élément de base de dispositif qui utilise un matériau de résine et comporte une couche de surface biocompatible sur une surface de résine de celui-ci, la couche de surface étant hautement adhésive à la surface de résine de l'élément de base de dispositif, et en conséquence, la biocompatibilité est hautement durable et la détérioration de l'élément de base de dispositif pendant la production est empêchée. Ce dispositif médical comprend: un élément de base de dispositif dont au moins une partie de sa surface est constituée d'un matériau de résine; un film de revêtement sec disposé sur la surface constituée du matériau de résine, le film de revêtement sec comprenant en tant que composant principal au moins un oxyde métallique choisi dans le groupe constitué par l'oxyde de silicium, l'oxyde de titane et l'oxyde d'aluminium; et une couche de surface disposée sur le film de revêtement sec, la couche de surface ayant un groupe biocompatible et formant une liaison covalente avec le film de revêtement sec.
PCT/JP2019/033992 2018-09-11 2019-08-29 Dispositif médical WO2020054454A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2020545908A JP7334738B2 (ja) 2018-09-11 2019-08-29 医療用デバイス

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2018169556 2018-09-11
JP2018-169556 2018-09-11

Publications (1)

Publication Number Publication Date
WO2020054454A1 true WO2020054454A1 (fr) 2020-03-19

Family

ID=69778290

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2019/033992 WO2020054454A1 (fr) 2018-09-11 2019-08-29 Dispositif médical

Country Status (2)

Country Link
JP (1) JP7334738B2 (fr)
WO (1) WO2020054454A1 (fr)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006121573A1 (fr) * 2005-05-05 2006-11-16 Applied Microstructures, Inc. Depot chimique en phase vapeur commande servant a appliquer des revetements biocompatibles sur des dispositifs medicaux
JP2013226284A (ja) * 2012-04-26 2013-11-07 Dainippon Printing Co Ltd 物質の吸着が抑制された管状基材およびその製造方法
JP2017093908A (ja) * 2015-11-26 2017-06-01 住友ゴム工業株式会社 金属医療用具及びその製造方法
JP2017125241A (ja) * 2016-01-14 2017-07-20 コニカミノルタ株式会社 機能性フィルムおよびこれを含む量子ドット（ｑｄ）含有積層部材の製造方法
JP2017164315A (ja) * 2016-03-16 2017-09-21 旭硝子株式会社 医療用デバイスの製造方法
JP2018070716A (ja) * 2016-10-27 2018-05-10 住友ベークライト株式会社 共重合体、生体分子捕捉用の生理活性物質固定化ポリマー、コーティング組成物、および物品
WO2019151265A1 (fr) * 2018-02-01 2019-08-08 Ａｇｃ株式会社 Matériau de base et copolymère
WO2019151114A1 (fr) * 2018-02-01 2019-08-08 Ａｇｃ株式会社 Récipient de culture cellulaire

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006121573A1 (fr) * 2005-05-05 2006-11-16 Applied Microstructures, Inc. Depot chimique en phase vapeur commande servant a appliquer des revetements biocompatibles sur des dispositifs medicaux
JP2013226284A (ja) * 2012-04-26 2013-11-07 Dainippon Printing Co Ltd 物質の吸着が抑制された管状基材およびその製造方法
JP2017093908A (ja) * 2015-11-26 2017-06-01 住友ゴム工業株式会社 金属医療用具及びその製造方法
JP2017125241A (ja) * 2016-01-14 2017-07-20 コニカミノルタ株式会社 機能性フィルムおよびこれを含む量子ドット（ｑｄ）含有積層部材の製造方法
JP2017164315A (ja) * 2016-03-16 2017-09-21 旭硝子株式会社 医療用デバイスの製造方法
JP2018070716A (ja) * 2016-10-27 2018-05-10 住友ベークライト株式会社 共重合体、生体分子捕捉用の生理活性物質固定化ポリマー、コーティング組成物、および物品
WO2019151265A1 (fr) * 2018-02-01 2019-08-08 Ａｇｃ株式会社 Matériau de base et copolymère
WO2019151114A1 (fr) * 2018-02-01 2019-08-08 Ａｇｃ株式会社 Récipient de culture cellulaire

Also Published As

Publication number Publication date
JPWO2020054454A1 (ja) 2021-09-16
JP7334738B2 (ja) 2023-08-29

Similar Documents

Publication Publication Date Title
JP7368446B2 (ja) 親水性共重合体および医療用具
US20080312356A1 (en) Vapor-deposited biocompatible coatings which adhere to various plastics and metal
KR20090084847A (ko) 실리콘 및 특정 폴리포스파젠을 포함하는 조성물 및 장치
WO2013061747A1 (fr) Procédé de production de substrat revêtu
US20200346972A1 (en) Base material and copolymer
WO2019142710A1 (fr) Matériau de revêtement médical et instrument médical utilisant ledit matériau de revêtement médical
SA111320686B1 (ar) بوليمرات مشتركة وظيفية من أيزو أولفينات وثاني أولفينات وإستخدامها كعوامل توافق
US20220168475A1 (en) Medical device and method for manufacturing same
JP2014040373A (ja) 含フッ素化合物、コーティング用組成物、撥水層付き基材およびその製造方法
WO2020054454A1 (fr) Dispositif médical
CN109666403A (zh) 抗粘附涂层组合物及抗粘附涂层
JP4277731B2 (ja) 気体分離膜
EP3013876B1 (fr) Composition durcissable à l'humidité, son procédé d'utilisation et article composite
WO2019240093A1 (fr) Article résistant à l'encrassement et son procédé de production
JP7192856B2 (ja) 医療用デバイス
US20220176022A1 (en) Medical device and method for manufacturing same
WO2022202805A1 (fr) Copolymère hydrophile et instrument médical
WO2021095753A1 (fr) Composé polymère et composition de revêtement
CN118843648A (zh) 共聚物、组合物和物品
WO2023113031A1 (fr) Filtre, procédé de production de filtre, matériau de revêtement, outil de capture de substance microscopique, dispositif de détection de substance microscopique, procédé de capture d'une substance microscopique, et composé
JP2018068808A (ja) 気管用チューブ
JP2018145249A (ja) 親水撥油性コンポジット
US20240002678A1 (en) Surface treatment agent and method of producing substrate having surface-treated layer
JP2017203062A (ja) 新規ポリマー
JP2015054180A (ja) 医療用器具または医療用材料

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19860478

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2020545908

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19860478

Country of ref document: EP

Kind code of ref document: A1