WO2020013010A1 - Fluorine-containing polymer, film, and medical instrument - Google Patents

Fluorine-containing polymer, film, and medical instrument Download PDF

Info

Publication number
WO2020013010A1
WO2020013010A1 PCT/JP2019/026123 JP2019026123W WO2020013010A1 WO 2020013010 A1 WO2020013010 A1 WO 2020013010A1 JP 2019026123 W JP2019026123 W JP 2019026123W WO 2020013010 A1 WO2020013010 A1 WO 2020013010A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluorine
fluorinated
mass
polymer
moiety
Prior art date
Application number
PCT/JP2019/026123
Other languages
French (fr)
Japanese (ja)
Inventor
亮平 小口
今日子 山本
賢 田中
ヤンコヴァ アタナソヴァ カチャ
Original Assignee
Ａｇｃ株式会社
国立大学法人九州大学
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, 国立大学法人九州大学 filed Critical Ａｇｃ株式会社
Publication of WO2020013010A1 publication Critical patent/WO2020013010A1/en

Links

Classifications

    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
    • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
    • C08F20/10—Esters
    • C08F20/22—Esters containing halogen
    • C08F20/24—Esters containing halogen containing perhaloalkyl radicals
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
    • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
    • C08F20/10—Esters
    • C08F20/26—Esters containing oxygen in addition to the carboxy oxygen
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F4/00—Polymerisation catalysts
    • C08F4/40—Redox systems

Definitions

  • the present invention relates to a fluoropolymer, a membrane, and a medical device.
  • the base material of the medical device is made of various polymer materials. Medical devices come in contact with biological components such as blood and proteins when used, and therefore, are required to have excellent biocompatibility in which biological components such as proteins are not easily adsorbed. Therefore, it has been proposed to coat the surface of a substrate with a polymer having good biocompatibility such as poly (2-hydroxyethyl methacrylate) (PHEMA). However, the biocompatibility obtained with PHEMA is not sufficient.
  • PHEMA poly (2-hydroxyethyl methacrylate
  • Non-Patent Document 1 discloses that by introducing a small amount of a unit based on a monomer having an amino group into PHEMA, the amount of intermediate water correlated with biocompatibility is increased.
  • Non-Patent Document 2 discloses that by introducing a small amount of a unit based on polyfluoroalkyl methacrylate having CF 3 (CF 2 ) 7 (CH 2 ) 2 — into PHEMA, the effect of suppressing protein adsorption is enhanced. I have.
  • Non-Patent Document 1 is inferior in water resistance and may be eluted during use.
  • the polymer of Non-Patent Document 2 introduces a small amount of a unit based on polyfluoroalkyl methacrylate having CF 3 (CF 2 ) 7 (CH 2 ) 2 — into PHEMA, but has a long fluorine side chain. Since a post-polymerization reaction is involved, a technique for obtaining a polymer is complicated, and there is a concern about variation in the polymerization reaction. In addition, CF 3 (CF 2 ) 7 (CH 2 ) 2 -side chain has high crystallinity, low molecular flexibility, and the obtained biocompatibility is not yet sufficient. In order to be applied to a medical device to be used, further improvement in characteristics is required.
  • An object of the present invention is to provide a fluorinated polymer having excellent water resistance, which is less likely to adsorb biological components such as proteins, and which has excellent biocompatibility, a membrane using the fluorinated polymer, and a medical device. I do.
  • a fluorinated polymer having a unit based on 2-hydroxyethyl methacrylate and a fluorinated moiety The content of the unit based on the 2-hydroxyethyl methacrylate is 50% by mass or more based on the total mass of the fluoropolymer,
  • the fluorinated moiety is a moiety based on a fluorinated polymerization initiator having a polyfluoroalkyl group having 1 to 16 carbon atoms to which a fluorine atom is bonded, a moiety based on a fluorinated macroinitiator, a fluorinated monomer.
  • the fluoropolymer of [1] wherein the amount of intermediate water measured by a differential scanning calorimetry is 0.5% by mass or more.
  • a medical device having a base material and the film of [3] or [4] formed on the base material.
  • the present invention it is possible to provide a fluorinated polymer which is excellent in water resistance and which is not easily adsorbed by biological components such as proteins, and which is excellent in biocompatibility, a membrane using the fluorinated polymer, and a medical device.
  • “Monomer” refers to a compound having a polymerizable unsaturated bond. Examples of the polymerizable unsaturated bond include a double bond and a triple bond between carbon atoms.
  • the “fluorinated monomer” refers to a monomer having a fluorine atom (however, excluding a fluorinated macromonomer).
  • Fluorine-containing macromonomer refers to a polymer compound having a fluorine atom and a polymerizable unsaturated bond and having a molecular weight of 5000 or more.
  • the “unit based on the monomer” refers to an atomic group formed directly by polymerization of a monomer and an atomic group obtained by chemically converting a part of the atomic group. The same applies to the “unit based on a fluorinated macromonomer”.
  • “Fluorine-containing polymerization initiator” refers to a polymerization initiator for atom transfer radical polymerization (ATRP) having a fluorine atom.
  • “Fluorine-containing macroinitiator” refers to an ATRP polymerization initiator having one or more units based on a fluorine-containing monomer. The fluorine-containing macroinitiator does not include a unit based on a monomer having no fluorine atom.
  • All the units based on one or more fluorine-containing monomers bonded to the polymerization initiator of ATRP without going through the units based on the monomer having no fluorine atom are all included in the fluorine-containing macroinitiator.
  • Melting point is the temperature corresponding to the maximum value of the melting peak of the polymer measured by the differential scanning calorimetry (DSC) method.
  • Glass transition temperature is an intermediate glass transition temperature determined from a DSC curve of a polymer measured by a differential scanning calorimetry (DSC) method. For example, under the conditions of a nitrogen flow rate of 50 mL / min and 5.0 ° C./min, (i) heating from 30 ° C.
  • the fluorinated polymer of the present invention includes units based on 2-hydroxyethyl methacrylate (HEMA) (hereinafter also referred to as “HEMA units”) and the following units.
  • HEMA 2-hydroxyethyl methacrylate
  • a fluorine portion hereinafter also referred to as “fluorine-containing portion F”).
  • a polyfluoroalkyl group having 1 to 6 carbon atoms to which a fluorine atom is bonded is also referred to as “R f group”.
  • the fluorinated portion F is a portion based on a fluorinated polymerization initiator having an R f group (hereinafter, also referred to as “initiator F1”), and a fluorinated macroinitiator (hereinafter, also referred to as “macro initiator F2”).
  • a unit based on a fluorinated monomer hereinafter also referred to as “monomer F3”
  • a unit based on a fluorinated macromonomer hereinafter also referred to as “macromonomer F4”. It is at least one selected.
  • the R f group may be linear or branched.
  • the number of carbon atoms to which a fluorine atom in the R f group is bonded is preferably 1 to 16, more preferably 1 to 10, and particularly preferably 1.
  • the number of carbon atoms in the R f group is preferably 1 to 8, more preferably 2 to 8.
  • — (CH 2 ) a1 — (CF 2 ) a2 F (where a1 is 1 to 4 and a2 is 1 to 6) is preferable.
  • —CH 2 CF 3 , —CH 2 CH 2 CF 2 CF 2 CF 2 CF 3, and —CH 2 CH 2 CF 2 CF 2 CF 2 CF 2 CF 3 can be exemplified.
  • -CH 2 CF 3 and -CH 2 CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3 are preferable, and -CH 2 CF 3 is particularly preferable.
  • the melting point (Tm) of the initiator F1 is preferably 37 ° C. or lower, more preferably ⁇ 100 to 37 ° C., and still more preferably ⁇ 80 to 0 ° C.
  • Tm melting point
  • the melting point (Tm) of the initiator F1 is preferably 37 ° C. or lower, more preferably ⁇ 100 to 37 ° C., and still more preferably ⁇ 80 to 0 ° C.
  • Tm of the initiator F1 is equal to or less than the upper limit of the above range, a biological component such as a protein is not easily adsorbed to the present fluoropolymer.
  • the Tm of the initiator F1 is equal to or more than the lower limit of the above range, the initiator F1 has a sufficient viscosity at room temperature and a sufficient film strength can be obtained.
  • an ATRP polymerization initiator having an Rf group is preferable, and the following compound F11 is more preferable.
  • the initiator F1 include the following compounds. CH 3 CBr (CH 3) COO -CH 2 CF 3, CH 3 CBr (CH 3) COO-CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3 CF 3, CH 3 CBr (CH 3) COO-CH 2 (CF 2 ) 8 CH 2 —OCOCBr (CH 3 ) CH 3 , CH 3 CBr (CH 3 ) COO—C 6 F 4 —C 6 F 5 , CH 3 CBr (CH 3 ) COO— (C 6 F 4 ) 2 -OCOCBr (CH 3 ) CH 3 .
  • CH 3 CBr (CH 3 ) COO—CH 2 CF 3 and CH 3 CBr (CH 3 ) COO—CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3 are preferable as the initiator F1.
  • CH 3 CBr (CH 3 ) COO—CH 2 CF 3 is more preferred.
  • Macroinitiator F2 is a fluorinated macroinitiator having an R f group.
  • the glass transition temperature (Tg) of the macroinitiator F2 is preferably 37 ° C. or lower, more preferably ⁇ 100 to 37 ° C., and still more preferably ⁇ 80 to 0 ° C.
  • Tg of the macroinitiator F2 is less than or equal to the upper limit of the above range, biological components such as proteins are not easily adsorbed to the present fluoropolymer.
  • the Tg of the macroinitiator F2 is equal to or higher than the lower limit of the above range, the macroinitiator has sufficient viscosity at room temperature and sufficient film strength.
  • the macroinitiator F2 include Br (CH 2 —CH (COOCH 2 CF 3 )) n —C (CH 3 ) 2 —COO—CH 2 CH 3 and Br (CH 2 —CH (CF 2 CF 2) CF 2 CF 2 CF 2 CF 3 )) n —C (CH 3 ) 2 —COO—CH 2 CH 3 .
  • Br (CH 2 —CH (COOCH 2 CF 3 )) n —C (CH 3 ) 2 —COO—CH 2 CH 3 is preferable. (However, n is 1 to 50.)
  • the monomer F3 is a fluorine-containing monomer having an Rf group. However, the unit based on the monomer F3 does not include the unit based on the fluorinated monomer constituting the fluorinated macroinitiator.
  • the Tm of the monomer F3 is preferably 37 ° C. or lower, more preferably ⁇ 100 to 37 ° C., and still more preferably ⁇ 80 to 0 ° C. When the Tm of the monomer F3 is equal to or less than the upper limit of the above range, biological components such as proteins are not easily adsorbed to the present fluoropolymer. When the Tm of the monomer F3 is equal to or more than the lower limit of the above range, the monomer F3 has a sufficient viscosity at room temperature and a sufficient film strength can be obtained.
  • Examples of the monomer F3 include a polyfluoroalkyl (meth) acrylate and a polyfluoroether (meth) acrylate having an Rf group. Among them, a polyfluoroalkyl (meth) acrylate having an R f group is preferable, and the following compound F31 is more preferable.
  • R 1 in the above formula F31 is a hydrogen atom or a methyl group.
  • c1 is 1 to 4, and c2 is 1 to 6.
  • c1 is preferably 1 to 2.
  • c2 is preferably from 1 to 4, and more preferably 1.
  • the compound F31 include the following compounds. CH 2 CHCHCOOCH 2 CF 3 , CH 2 CC (CH 3 ) COOCH 2 CF 3 , CH 2 CHCHCOO (CH 2 ) 2 (CF 2 ) 5 —CF 3 , CH 2 CC (CH 3 ) COO (CH 2 ) 2 (CF 2 ) 5 —CF 3 and the like.
  • the unit based on the monomer F3 of the present fluorine-containing polymer may be one type, or two or more types.
  • the macromonomer F4 is a fluorine-containing macromonomer having an Rf group.
  • the Tg of the macromonomer F4 is preferably 37 ° C. or lower, more preferably ⁇ 100 to 37 ° C., and still more preferably ⁇ 80 to 0 ° C.
  • the Tg of the macromonomer F4 is equal to or less than the upper limit of the above range, biological components such as proteins are not easily adsorbed to the present fluoropolymer.
  • the Tg of the macromonomer F4 is equal to or more than the lower limit of the above range, the macromonomer F4 has sufficient viscosity at room temperature and sufficient film strength can be obtained.
  • CH 2 CHCHCOO (CH 2 ) 2 (CH 2 —CH (COOCH 2 CF 3 )) n H
  • CH 2 CHCHCOO (CH 2 ) 2 (CH 2 —CH (COOCH 2 CH 2 CF 2 CF 2) CF 2 CF 2 CF 2 CF 3 )) n H
  • n is 1 to 50.
  • the present fluorine-containing polymer may have a unit based on a non-fluorine-based monomer having no fluorine atom other than HEMA as long as the effect of the present invention is not impaired.
  • Non-fluorinated monomers other than HEMA include methoxyethyl acrylate (MEA), 2-hydroxyacrylate (HEA), polyethylene glycol acrylate (PEGA), tetrahydrofurfuryl acrylate (THFA), methyl methacrylate (MMA), and butyl methacrylate (BMA) and methoxyethyl methacrylate (MEMA).
  • the present fluorinated polymer has, as the fluorinated moiety F, any one of a moiety based on the initiator F1, a moiety based on the macroinitiator F2, a unit based on the monomer F3, and a unit based on the macromonomer F4. May be included, or two or more of these may be included.
  • the fluorinated polymer When the fluorinated polymer has a unit based on the monomer F3 or a unit based on the macromonomer F4 as the fluorinated moiety F, the fluorinated polymer may be a block copolymer, and a random copolymer. It may be.
  • a fluorinated polymer in which the fluorinated moiety F consists only of a unit based on the monomer F3 is preferable, and a random copolymer of HEMA and the monomer F3 is particularly preferable.
  • the content of the HEMA unit in the present fluoropolymer is 50% by mass or more, preferably 50 to 99% by mass, more preferably 75 to 99% by mass, based on the total mass of the present fluoropolymer. 90 to 99% by mass is more preferred.
  • the content of the HEMA unit is within the above range, it is difficult for biological components such as proteins to be adsorbed to the present fluoropolymer.
  • the content of the fluorinated moiety F in the present fluorinated polymer is 0.1 to 16% by mass, preferably 0.5 to 15% by mass, based on the total mass of the fluorinated polymer. 0 to 15% by mass is more preferred.
  • the content of the fluorinated moiety F is within the above range, biological components such as proteins are not easily adsorbed to the fluorinated polymer.
  • the total content of the fluorine-containing moiety F and the HEMA unit in the present fluorine-containing polymer is preferably 50.1% by mass or more, more preferably 75% by mass or more, based on the total mass of the present fluorine-containing polymer. 100% by weight is particularly preferred.
  • the number average molecular weight (Mn) of the fluoropolymer is preferably from 5,000 to 500,000, more preferably from 5,000 to 200,000.
  • Mn of the present fluorine-containing polymer is at least the lower limit of the above range, elution of low molecular weight components having low water resistance can be suppressed.
  • Mn of the present fluoropolymer is equal to or less than the upper limit of the above range, the viscosity is increased, the mobility of the molecule is reduced, and the possibility of difficulty in interacting with water is low.
  • the weight average molecular weight (Mw) of the fluoropolymer is preferably from 5,000 to 500,000, more preferably from 5,000 to 200,000.
  • Mw of the present fluoropolymer is at least the lower limit of the above range, elution of low molecular weight components having low water resistance can be suppressed.
  • Mw of the present fluoropolymer is equal to or less than the upper limit of the above range, the viscosity is increased, the mobility of the molecule is reduced, and the possibility that the molecule does not easily interact with water is low.
  • the molecular weight distribution (Mw / Mn) of the present fluoropolymer is preferably from 1.0 to 3.0, more preferably from 1.0 to 2.5.
  • Mw / Mn of the present fluoropolymer is equal to or less than the upper limit of the above range, lot-to-lot variation can be minimized.
  • the amount of intermediate water of the fluoropolymer measured by the DSC method is preferably 0.5% by mass or more, more preferably 5% by mass or more.
  • the amount of intermediate water of the present fluorinated polymer is not less than the lower limit, biological components such as proteins are less likely to be adsorbed.
  • the method for producing the present fluoropolymer is not particularly limited.
  • the initiator F1 or the macroinitiator F2 when used, at least one of the initiator F1 and the macroinitiator F2, HEMA, and a monomer F3, a macromonomer F4 and the like used as needed are added to the polymerization solvent, A method of performing ATRP starting from a radical portion generated from the initiator F1 or the macroinitiator F2 can be exemplified. ATRP is preferably performed in a deoxygenated environment.
  • azo compounds (2,2-azobisisobutyronitrile and the like), organic peroxides (isobutyryl peroxide and the like), HEMA, monomer A method in which at least one of the body F3 and the macromonomer F4 is added to a polymerization solvent and radical polymerization is performed can be exemplified.
  • the polymerization solvent is not particularly limited and includes ketones (acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), alcohols (methanol, 2-propyl alcohol, etc.), esters (ethyl acetate, butyl acetate, etc.), ethers (diisopropyl ether, tetrahydrofuran, Dioxane), glycol ethers (such as ethyl ether or methyl ether of ethylene glycol, propylene glycol, and dipropylene glycol) and derivatives thereof, aliphatic hydrocarbons, aromatic hydrocarbons, and halogenated hydrocarbons (perchloroethylene, trichloro-1).
  • ketones acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.
  • alcohols methanol, 2-propyl alcohol, etc.
  • esters ethyl acetate, butyl acetate
  • the total concentration of the monomer and the fluorinated macromonomer in the reaction solution in the polymerization reaction for obtaining the present fluorinated polymer is preferably from 5 to 50% by mass, particularly preferably from 10 to 30% by mass.
  • the total amount of the polymerization initiator and the fluorinated macroinitiator in the reaction solution is preferably 0.1 to 3 parts by mass, preferably 0.5 to 3 parts by mass, based on 100 parts by mass of the total amount of the monomer and the fluorinated macromonomer. 1.0 parts by mass is more preferred.
  • the polymerization temperature is preferably from 50 to 100 ° C, more preferably from 60 to 90 ° C.
  • the film of the present invention is a film containing the present fluoropolymer.
  • the film of the present invention may contain components other than the present fluoropolymer as long as the effects of the present invention are not impaired. Examples of other components include a leveling agent, a thermoplastic resin, a thermosetting resin, a photocurable resin, an ultraviolet absorber, and an antibacterial agent.
  • the content of the present fluoropolymer in the film of the present invention is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and preferably 1.0% by mass or more based on the total mass of the film. More preferred.
  • the bubble contact angle of the film surface of the film of the present invention in water is preferably 135 ° or more, more preferably 140 ° or more, even more preferably 150 ° or more.
  • the bubble contact angle on the membrane surface is equal to or larger than the lower limit, biological components such as proteins are not easily adsorbed on the membrane. The larger the bubble contact angle on the film surface, the better.
  • the bubble contact angle of the film surface in water is 135 ° or more. This makes it difficult for biological components such as proteins to be adsorbed to the membrane even when the amount of intermediate water of the present fluoropolymer is low.
  • the thickness of the film of the present invention is preferably 0.01 to 100 ⁇ m, more preferably 0.1 to 10 ⁇ m.
  • the film functions as a continuous film, and sufficient film strength can be obtained.
  • the thickness of the film is equal to or less than the upper limit of the above range, the utilization efficiency of the material is high.
  • the method for producing the film is not particularly limited.
  • a method in which a coating solution containing the present fluoropolymer is applied to the surface of a substrate and dried to form a film can be exemplified.
  • the solvent used for the coating solution is not particularly limited, and examples thereof include ethanol, methanol, acetone, chloroform, tetrahydrofuran, toluene, xylene, trifluoroethanol, hexafluoroisopropanol, methoxypropanol, and dimethylformamide.
  • the concentration of the present fluoropolymer in the coating solution is preferably 0.01 to 5.0% by mass, more preferably 0.1 to 3.0%. If the concentration of the present fluoropolymer is within the above range, it can be applied uniformly, so that a uniform film is easily formed.
  • the medical device of the present invention has a substrate and the film of the present invention formed on at least a part of the substrate.
  • a film may be limitedly formed in a partial region on the substrate, or the film may be entirely formed on the substrate.
  • the medical device of the present invention may have an intermediate layer between the substrate and the membrane. Examples of the intermediate layer include polymethacrylmethyl acrylate (PMMA).
  • the medical device refers to a device used for medical treatment, such as treatment, diagnosis, anatomical or biological examination, and is inserted or brought into contact with a living body such as a human body, or a component (blood or the like) removed from the living body. And any device that is brought into contact with.
  • the base material of the medical device of the present invention includes a cell culture container, a cell culture sheet, a cell capture filter, a vial, a plastic coated vial, a syringe, a plastic coated syringe, an ampoule, a plastic coated ampule, a cartridge, a bottle, a plastic coated bottle, and a pouch.
  • the material for forming the substrate is not particularly limited, and examples thereof include resins such as polystyrene, polycarbonate, and polypropylene, and glass.
  • a fluorine-containing polymer having a HEMA unit as a main component and a fluorine-containing moiety F having an Rf group at a specific ratio is used.
  • the present fluoropolymer is also useful for application to medical devices that are used repeatedly or used for a long time.
  • the present fluorinated polymer has a fluorinated portion F, it is excellent in water resistance as compared with a conventional polymer in which an amino group is introduced as in Non-Patent Document 1.
  • the factors that improve the biocompatibility of the present fluoropolymer are considered as follows.
  • free water, intermediate water, and antifreeze water are present in the water contained in the water-containing polymer. It is known that the greater the amount of intermediate water, the better the biocompatibility and the less likely it is for biological components such as proteins to be adsorbed. (M. Tanaka et al., Polym. J, 2013, 45, 701).
  • the fluorinated portion F since the fluorinated portion F is contained at a specific ratio, the hydration structure of the polymer when hydrated changes, and the free water decreases and the intermediate water increases. Conceivable.
  • the R f group contained in the fluorinated portion F of the present fluorinated polymer is shorter than CF 3 (CF 2 ) 7 (CH 2 ) 2 -in Non-Patent Document 2, and has low crystallinity. It is considered that the portion of the fluoropolymer that interacts with the intermediate water is likely to be efficiently oriented on the surface. From these facts, it is considered that the composition has excellent biocompatibility and the effect of suppressing adsorption of biological components such as proteins is enhanced.
  • the portion interacting with the intermediate water in the present fluoropolymer is more easily oriented on the membrane surface.
  • the effect of suppressing adsorption of biological components such as proteins is further enhanced.
  • the column configuration was such that Tosoh Super HZ4000, Super HZ3000, Super HZ2500, and Super HZ2000 were connected in series.
  • the molecular weight distribution (Mw / Mn) was calculated using Mw and Mn determined by GPC measurement.
  • composition of the polymer obtained in each example was calculated from the analysis result of 1 H NMR (manufactured by JEOL). NMR analysis was performed at room temperature (25 ° C.) using heavy DMSO (DMSO-d6) as a solvent.
  • W C ((W 1 ⁇ W 0 ) / W 1 ) ⁇ 100 Equation 1 (Where, in the above formula 1, W C is the moisture content (% by mass) of the sample, W 0 is the mass (g) of the sample after drying, and W 1 is the mass (g) of the sample before drying. is there.)
  • [Hydrophilic rate] 0.2 g of the polymer obtained in each example was dissolved in 1 mL of the solvent to prepare a sample solution.
  • a solvent methanol or THF was used.
  • a disk-shaped polyethylene terephthalate (PET) substrate 14 mm ⁇ was pre-washed with methanol.
  • the sample liquid was applied twice on the surface of the washed PET substrate using a spin coater and dried to form a film having a thickness of 0.05 ⁇ m. The interval between two application of the sample liquid was 15 minutes.
  • phosphate buffer solution PBS
  • 30 ⁇ L of a 1N NaOH aqueous solution containing 0.5% sodium dodecyl sulfate (SDS) was added into the well, and the mixture was kept at 37 ° C. for 2 hours, and the protein adsorbed on the membrane in the well was collected in the aqueous phase.
  • 150 ⁇ L of micro BCA reagent manufactured by Thermo Scientific
  • 120 ⁇ L of phosphate buffer PBS manufactured by Wako Pure Chemical Industries
  • HEMA 2-hydroxyethyl methacrylate.
  • 3FM 2,2,2-trifluoroethyl methacrylate.
  • AIBN 2,2-azobisisobutyronitrile.
  • DMF N, N-dimethylformamide.
  • Example 1 1.89 g of HEMA, 0.076 g of 3FM, 0.02 g of AIBN, and 9.79 mL of DMF were charged into a four-necked flask equipped with a stirrer, thermometer, Dimroth condenser, and nitrogen inlet tube. (25 ° C.). The mixture was heated to 80 ° C., stirred at 80 ° C. for 20 hours, and then cooled to room temperature. The obtained reaction mixture was added to 500 mL of diethyl ether to cause precipitation.
  • Example 2 Except that the charged amount of HEMA was changed to 1.73 g and the charged amount of 3FM to 0.11 g, the same procedure as in Example 1 was used to prepare a fluoropolymer P-2 which is a random copolymer of HEMA and 3FM. 1.86 g were obtained. Mn of the fluoropolymer P-2 was 20,000, Mw was 41,000, and Mw / Mn was 3.2. The content of the fluorinated moiety in the fluorinated polymer P-2 was 6.4% by mass.
  • Example 3 Except that the charged amount of HEMA was changed to 1.64 g, and the charged amount of 3FM was changed to 0.21 g, the same procedure as in Example 1 was used to prepare the fluoropolymer P-3 which is a random copolymer of HEMA and 3FM. 1.77 g were obtained. Mn of the fluoropolymer P-3 was 20,000, Mw was 41,000, and Mw / Mn was 3.2. The content of the fluorinated moiety in the fluorinated polymer P-3 was 12.6% by mass.
  • Example 1 In the same manner as in Example 1 except that 3FM was not used, 1.55 g of a polymer P-4 which was a homopolymer of HEMA was obtained. Mn of the polymer P-4 was 20,000, Mw was 41,000, and Mw / Mn was 3.2.
  • Table 1 shows the composition of the polymer of each example and the evaluation results.
  • the fluorinated polymers of Examples 1 to 3 having the fluorinated portion F at a specific ratio were Comparative Example 1 having no fluorinated portion and Comparative Example 2 having a high content of the fluorinated portion. And the polymer of Comparative Example 3 having no HMEA unit had a smaller amount of adsorbed protein and was excellent in biocompatibility.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Vascular Medicine (AREA)
  • Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Provided are: a fluorine-containing polymer that has excellent water resistance, resists adherence of biological components such as proteins, and has excellent biocompatibility; a film that uses said fluorine-containing polymer; and a medical instrument. This fluorine-containing polymer has a unit based on 2-hydroxyethyl methacrylate, and a fluorine-containing moiety. The content of the unit based on 2-hydroxyethyl methacrylate is at least 50% by mass with respect to the total mass of the fluorine-containing polymer. The fluorine-containing moiety is at least one selected from the group consisting of: a moiety based on a fluorine-containing polymerization initiator having a polyfluoroalkyl group with 1 to 16 carbon atoms that are bonded to fluorine atoms; a moiety based on a fluorine-containing macro initiator; a unit based on a fluorine-containing monomer; and a unit based on a fluorine-containing macro monomer. The content of the fluorine-containing moiety falls within the range of 0.1 to 16% by mass, inclusive, with respect to the total mass of the fluorine-containing polymer.

Description

含フッ素重合体、膜及び医療用具Fluoropolymers, membranes and medical devices
　本発明は、含フッ素重合体、膜及び医療用具に関する。 The present invention relates to a fluoropolymer, a membrane, and a medical device.
　医療用具を構成する基材は、各種の高分子材料で形成されている。医療用具は、使用時に血液、タンパク質等の生体成分と接触するため、タンパク質等の生体成分が吸着しにくい優れた生体親和性が要求される。そこで、ポリ（２－ヒドロキシエチルメタクリレート）（ＰＨＥＭＡ）等の生体親和性が良好な重合体で基材表面を被覆することが提案されている。しかし、ＰＨＥＭＡで得られる生体親和性は充分ではない。 基材 The base material of the medical device is made of various polymer materials. Medical devices come in contact with biological components such as blood and proteins when used, and therefore, are required to have excellent biocompatibility in which biological components such as proteins are not easily adsorbed. Therefore, it has been proposed to coat the surface of a substrate with a polymer having good biocompatibility such as poly (2-hydroxyethyl methacrylate) (PHEMA). However, the biocompatibility obtained with PHEMA is not sufficient.
　ＰＨＥＭＡの生体親和性を向上させる方法としては、２－ヒドロキシエチルメタクリレート（ＨＥＭＡ）以外の単量体に基づく単位をＰＨＥＭＡに少量導入する方法が提案されている。非特許文献１には、アミノ基を有する単量体に基づく単位をＰＨＥＭＡに少量導入することで、生体親和性と相関がある中間水量が増加することが開示されている。非特許文献２には、ＣＦ３（ＣＦ２）７（ＣＨ２）２－を有するポリフルオロアルキルメタクリレートに基づく単位をＰＨＥＭＡに少量導入することで、タンパク質の吸着抑制効果が高まることが開示されている。 As a method for improving the biocompatibility of PHEMA, there has been proposed a method of introducing a small amount of a unit based on a monomer other than 2-hydroxyethyl methacrylate (HEMA) into PHEMA. Non-Patent Document 1 discloses that by introducing a small amount of a unit based on a monomer having an amino group into PHEMA, the amount of intermediate water correlated with biocompatibility is increased. Non-Patent Document 2 discloses that by introducing a small amount of a unit based on polyfluoroalkyl methacrylate having CF 3 (CF 2 ) 7 (CH 2 ) 2 — into PHEMA, the effect of suppressing protein adsorption is enhanced. I have.
　しかし、非特許文献１の重合体は、耐水性に劣り、使用時に溶出するおそれがある。非特許文献２の重合体は、ＣＦ３（ＣＦ２）７（ＣＨ２）２－を有するポリフルオロアルキルメタクリレートに基づく単位をＰＨＥＭＡに少量導入しているが、長いフッ素側鎖を有するがゆえに、後重合反応を伴うため重合体を得る手法が煩雑であるし、重合反応のばらつきが懸念される。またＣＦ３（ＣＦ２）７（ＣＨ２）２－側鎖は結晶性が高いため、分子柔軟性が低く、得られる生体親和性がまだ充分とは言えず、繰り返し使用したり、長時間使用したりする医療用具に適用するには、さらなる特性改善が求められる。 However, the polymer of Non-Patent Document 1 is inferior in water resistance and may be eluted during use. The polymer of Non-Patent Document 2 introduces a small amount of a unit based on polyfluoroalkyl methacrylate having CF 3 (CF 2 ) 7 (CH 2 ) 2 — into PHEMA, but has a long fluorine side chain. Since a post-polymerization reaction is involved, a technique for obtaining a polymer is complicated, and there is a concern about variation in the polymerization reaction. In addition, CF 3 (CF 2 ) 7 (CH 2 ) 2 -side chain has high crystallinity, low molecular flexibility, and the obtained biocompatibility is not yet sufficient. In order to be applied to a medical device to be used, further improvement in characteristics is required.
　本発明は、耐水性に優れ、またタンパク質等の生体成分が吸着しにくい、生体親和性に優れた含フッ素重合体、前記含フッ素重合体を用いた膜及び医療用具を提供することを目的とする。 An object of the present invention is to provide a fluorinated polymer having excellent water resistance, which is less likely to adsorb biological components such as proteins, and which has excellent biocompatibility, a membrane using the fluorinated polymer, and a medical device. I do.
　本発明は、以下の構成を有する。
［１］２－ヒドロキシエチルメタクリレートに基づく単位と、含フッ素部分とを有する含フッ素重合体であって、
　前記２－ヒドロキシエチルメタクリレートに基づく単位の含有量が、前記含フッ素重合体の総質量に対して５０質量％以上であり、
　前記含フッ素部分が、フッ素原子が結合している炭素原子の数が１～１６のポリフルオロアルキル基を有する含フッ素重合開始剤に基づく部分、含フッ素マクロ開始剤に基づく部分、含フッ素単量体に基づく単位、及び含フッ素マクロモノマーに基づく単位からなる群から選ばれる少なくとも１種であり、
　前記含フッ素部分の含有量が、前記含フッ素重合体の総質量に対して０．１～１６質量％である、含フッ素重合体。
［２］示差走査熱量法で測定される中間水量が０．５質量％以上である、［１］の含フッ素重合体。
［３］［１］又は［２］の含フッ素重合体を含む膜。
［４］水中における膜表面の気泡接触角が１３５°以上である、［３］の膜。
［５］基材と、前記基材上に形成された［３］又は［４］の膜とを有する医療用具。 The present invention has the following configuration.
[1] A fluorinated polymer having a unit based on 2-hydroxyethyl methacrylate and a fluorinated moiety,
The content of the unit based on the 2-hydroxyethyl methacrylate is 50% by mass or more based on the total mass of the fluoropolymer,
The fluorinated moiety is a moiety based on a fluorinated polymerization initiator having a polyfluoroalkyl group having 1 to 16 carbon atoms to which a fluorine atom is bonded, a moiety based on a fluorinated macroinitiator, a fluorinated monomer. At least one selected from the group consisting of units based on a body, and units based on a fluorinated macromonomer,
A fluorinated polymer, wherein the content of the fluorinated moiety is 0.1 to 16% by mass relative to the total mass of the fluorinated polymer.
[2] The fluoropolymer of [1], wherein the amount of intermediate water measured by a differential scanning calorimetry is 0.5% by mass or more.
[3] A film containing the fluoropolymer of [1] or [2].
[4] The film of [3], wherein the contact angle of bubbles on the film surface in water is 135 ° or more.
[5] A medical device having a base material and the film of [3] or [4] formed on the base material.
　本発明によれば、耐水性に優れ、またタンパク質等の生体成分が吸着しにくい、生体親和性に優れた含フッ素重合体、前記含フッ素重合体を用いた膜及び医療用具を提供できる。 According to the present invention, it is possible to provide a fluorinated polymer which is excellent in water resistance and which is not easily adsorbed by biological components such as proteins, and which is excellent in biocompatibility, a membrane using the fluorinated polymer, and a medical device.
　本明細書における以下の用語の定義は、以下の通りである。
　「単量体」とは、重合性不飽和結合を有する化合物を指す。重合性不飽和結合としては、炭素原子間の二重結合、三重結合が例示される。
　「含フッ素単量体」とは、フッ素原子を有する単量体（ただし、含フッ素マクロモノマーを除く。）を指す。
　「含フッ素マクロモノマー」とは、フッ素原子及び重合性不飽和結合を有する分子量が５０００以上の高分子化合物を指す。
　「単量体に基づく単位」とは、単量体が重合することで、直接形成される原子団と、前記原子団の一部を化学変換することで得られる原子団を指す。「含フッ素マクロモノマーに基づく単位」も同様である。
　「含フッ素重合開始剤」とは、フッ素原子を有する原子移動ラジカル重合（ＡＴＲＰ）の重合開始剤を指す。
　「含フッ素マクロ開始剤」とは、含フッ素単量体に基づく単位を１個以上有するＡＴＲＰの重合開始剤を指す。含フッ素マクロ開始剤には、フッ素原子を有しない単量体に基づく単位は含まない。フッ素原子を有しない単量体に基づく単位を介さずにＡＴＲＰの重合開始剤と結合している１個以上の含フッ素単量体に基づく単位は、すべて含フッ素マクロ開始剤に含まれる。
　「融点」とは、示差走査熱量（ＤＳＣ）法で測定した重合体の融解ピークの最大値に対応する温度である。
　「ガラス転移温度」とは、示差走査熱量（ＤＳＣ）法で測定した重合体のＤＳＣ曲線から求められる中間ガラス転移温度である。例えば、窒素流量５０ｍＬ／分、５．０℃／分の条件で、（ｉ）３０℃から１００℃まで加熱、（ｉｉ）１００℃から－８０℃まで冷却、（ｉｉｉ）－８０℃から１００℃まで加熱、（ｉｖ）１００℃から３０℃まで冷却する温度プログラムを実施し、前記（ｉｉｉ）において観察されるＴｇを求める。
　「中間水」とは、含水させた重合体に含まれる水のうち、重合体と相互作用せず水分子本来の挙動を示す自由水と、重合体と強く相互作用して－８０℃でも凍結しない不凍水との中間的な挙動を示す水を指す。
　「（メタ）アクリレート」とは、アクリレート及びメタクリレートの総称である。
　また、本明細書において、数値範囲を表す値は、その範囲の上限値又は下限値を含む。　明細書中においては、式Ｆ１１で表される化合物を化合物Ｆ１１と記す。他の式で表される化合物も同様に記す。 The definitions of the following terms in the present specification are as follows.
“Monomer” refers to a compound having a polymerizable unsaturated bond. Examples of the polymerizable unsaturated bond include a double bond and a triple bond between carbon atoms.
The “fluorinated monomer” refers to a monomer having a fluorine atom (however, excluding a fluorinated macromonomer).
"Fluorine-containing macromonomer" refers to a polymer compound having a fluorine atom and a polymerizable unsaturated bond and having a molecular weight of 5000 or more.
The “unit based on the monomer” refers to an atomic group formed directly by polymerization of a monomer and an atomic group obtained by chemically converting a part of the atomic group. The same applies to the “unit based on a fluorinated macromonomer”.
"Fluorine-containing polymerization initiator" refers to a polymerization initiator for atom transfer radical polymerization (ATRP) having a fluorine atom.
“Fluorine-containing macroinitiator” refers to an ATRP polymerization initiator having one or more units based on a fluorine-containing monomer. The fluorine-containing macroinitiator does not include a unit based on a monomer having no fluorine atom. All the units based on one or more fluorine-containing monomers bonded to the polymerization initiator of ATRP without going through the units based on the monomer having no fluorine atom are all included in the fluorine-containing macroinitiator.
"Melting point" is the temperature corresponding to the maximum value of the melting peak of the polymer measured by the differential scanning calorimetry (DSC) method.
“Glass transition temperature” is an intermediate glass transition temperature determined from a DSC curve of a polymer measured by a differential scanning calorimetry (DSC) method. For example, under the conditions of a nitrogen flow rate of 50 mL / min and 5.0 ° C./min, (i) heating from 30 ° C. to 100 ° C., (ii) cooling from 100 ° C. to −80 ° C., and (iii) −80 ° C. to 100 ° C. And (iv) a temperature program of cooling from 100 ° C. to 30 ° C. to determine the Tg observed in (iii) above.
"Intermediate water" refers to the free water that does not interact with the polymer but shows the original behavior of water molecules, and that interacts strongly with the polymer and freezes at -80 ° C. Refers to water that behaves in the middle of antifreeze water.
“(Meth) acrylate” is a general term for acrylate and methacrylate.
In this specification, a value representing a numerical range includes an upper limit or a lower limit of the range. In the specification, the compound represented by the formula F11 is referred to as compound F11. The same applies to compounds represented by other formulas.
［含フッ素重合体］
　本発明の含フッ素重合体（以下、「本含フッ素重合体」とも記す。）は、２－ヒドロキシエチルメタクリレート（ＨＥＭＡ）に基づく単位（以下、「ＨＥＭＡ単位」とも記す。）と、後述する含フッ素部分（以下、「含フッ素部分Ｆ」とも記す。）とを有する。 [Fluorine-containing polymer]
The fluorinated polymer of the present invention (hereinafter also referred to as “the present fluorinated polymer”) includes units based on 2-hydroxyethyl methacrylate (HEMA) (hereinafter also referred to as “HEMA units”) and the following units. A fluorine portion (hereinafter also referred to as “fluorine-containing portion F”).
　以下、フッ素原子が結合している炭素原子の数が１～６のポリフルオロアルキル基を「Ｒｆ基」とも記す。
　含フッ素部分Ｆは、Ｒｆ基を有する含フッ素重合開始剤（以下、「開始剤Ｆ１」とも記す。）に基づく部分、含フッ素マクロ開始剤（以下、「マクロ開始剤Ｆ２」とも記す。）に基づく部分、含フッ素単量体（以下、「単量体Ｆ３」とも記す。）に基づく単位、及び含フッ素マクロモノマー（以下、「マクロモノマーＦ４」とも記す。）に基づく単位からなる群から選ばれる少なくとも１種である。 Hereinafter, a polyfluoroalkyl group having 1 to 6 carbon atoms to which a fluorine atom is bonded is also referred to as “R f group”.
The fluorinated portion F is a portion based on a fluorinated polymerization initiator having an R f group (hereinafter, also referred to as “initiator F1”), and a fluorinated macroinitiator (hereinafter, also referred to as “macro initiator F2”). , A unit based on a fluorinated monomer (hereinafter also referred to as “monomer F3”), and a unit based on a fluorinated macromonomer (hereinafter also referred to as “macromonomer F4”). It is at least one selected.
　Ｒｆ基は、直鎖状であってもよく、分岐鎖状であってもよい。
　Ｒｆ基におけるフッ素原子が結合している炭素原子の数は、１～１６が好ましく、１～１０がより好ましく、１が特に好ましい。
　Ｒｆ基の炭素原子数は、１～８が好ましく、２～８がより好ましい。 The R f group may be linear or branched.
The number of carbon atoms to which a fluorine atom in the R f group is bonded is preferably 1 to 16, more preferably 1 to 10, and particularly preferably 1.
The number of carbon atoms in the R f group is preferably 1 to 8, more preferably 2 to 8.
　Ｒｆ基としては、－（ＣＨ２）ａ１－（ＣＦ２）ａ２Ｆ（ただし、ａ１は１～４であり、ａ２は１～６である。）が好ましい。具体的には、－ＣＨ２ＣＦ３、－ＣＨ２ＣＨ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３、－ＣＨ２ＣＨ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３を例示できる。なかでも、－ＣＨ２ＣＦ３、－ＣＨ２ＣＨ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３が好ましく、－ＣＨ２ＣＦ３が特に好ましい。 As the R f group, — (CH 2 ) a1 — (CF 2 ) a2 F (where a1 is 1 to 4 and a2 is 1 to 6) is preferable. Specifically, —CH 2 CF 3 , —CH 2 CH 2 CF 2 CF 2 CF 2 CF 3, and —CH 2 CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3 can be exemplified. Among them, -CH 2 CF 3 and -CH 2 CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3 are preferable, and -CH 2 CF 3 is particularly preferable.
　開始剤Ｆ１の融点（Ｔｍ）は、３７℃以下が好ましく、－１００～３７℃がより好ましく、－８０～０℃がさらに好ましい。開始剤Ｆ１のＴｍが前記範囲の上限値以下であれば、本含フッ素重合体にタンパク質等の生体成分が吸着しにくい。開始剤Ｆ１のＴｍが前記範囲の下限値以上であれば、室温で充分な粘度を有し、充分な膜強度が得られる。 融 点 The melting point (Tm) of the initiator F1 is preferably 37 ° C. or lower, more preferably −100 to 37 ° C., and still more preferably −80 to 0 ° C. When the Tm of the initiator F1 is equal to or less than the upper limit of the above range, a biological component such as a protein is not easily adsorbed to the present fluoropolymer. When the Tm of the initiator F1 is equal to or more than the lower limit of the above range, the initiator F1 has a sufficient viscosity at room temperature and a sufficient film strength can be obtained.
　開始剤Ｆ１としては、Ｒｆ基を有するＡＴＲＰの重合開始剤が好ましく、以下の化合物Ｆ１１がより好ましい。 As the initiator F1, an ATRP polymerization initiator having an Rf group is preferable, and the following compound F11 is more preferable.
Figure JPOXMLDOC01-appb-C000001
Figure JPOXMLDOC01-appb-C000001
　開始剤Ｆ１の具体例としては、以下の化合物を例示できる。
　ＣＨ３ＣＢｒ（ＣＨ３）ＣＯＯ－ＣＨ２ＣＦ３、ＣＨ３ＣＢｒ（ＣＨ３）ＣＯＯ－ＣＨ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３、ＣＨ３ＣＢｒ（ＣＨ３）ＣＯＯ－ＣＨ２（ＣＦ２）８ＣＨ２－ＯＣＯＣＢｒ（ＣＨ３）ＣＨ３、ＣＨ３ＣＢｒ（ＣＨ３）ＣＯＯ－Ｃ６Ｆ４－Ｃ６Ｆ５、ＣＨ３ＣＢｒ（ＣＨ３）ＣＯＯ－（Ｃ６Ｆ４）２－ＯＣＯＣＢｒ（ＣＨ３）ＣＨ３。
　なかでも、開始剤Ｆ１としては、ＣＨ３ＣＢｒ（ＣＨ３）ＣＯＯ－ＣＨ２ＣＦ３、ＣＨ３ＣＢｒ（ＣＨ３）ＣＯＯ－ＣＨ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３が好ましく、ＣＨ３ＣＢｒ（ＣＨ３）ＣＯＯ－ＣＨ２ＣＦ３がより好ましい。 Specific examples of the initiator F1 include the following compounds.
CH 3 CBr (CH 3) COO -CH 2 CF 3, CH 3 CBr (CH 3) COO-CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3, CH 3 CBr (CH 3) COO-CH 2 (CF 2 ) 8 CH 2 —OCOCBr (CH 3 ) CH 3 , CH 3 CBr (CH 3 ) COO—C 6 F 4 —C 6 F 5 , CH 3 CBr (CH 3 ) COO— (C 6 F 4 ) 2 -OCOCBr (CH 3 ) CH 3 .
Among them, CH 3 CBr (CH 3 ) COO—CH 2 CF 3 and CH 3 CBr (CH 3 ) COO—CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3 are preferable as the initiator F1. , CH 3 CBr (CH 3 ) COO—CH 2 CF 3 is more preferred.
　マクロ開始剤Ｆ２は、Ｒｆ基を有する含フッ素マクロ開始剤である。
　マクロ開始剤Ｆ２のガラス転移温度（Ｔｇ）は、３７℃以下が好ましく、－１００～３７℃がより好ましく、－８０～０℃がさらに好ましい。マクロ開始剤Ｆ２のＴｇが前記範囲の上限値以下であれば、本含フッ素重合体にタンパク質等の生体成分が吸着しにくい。マクロ開始剤Ｆ２のＴｇが前記範囲の下限値以上であれば、室温で充分な粘度を有し、充分な膜強度が得られる。 Macroinitiator F2 is a fluorinated macroinitiator having an R f group.
The glass transition temperature (Tg) of the macroinitiator F2 is preferably 37 ° C. or lower, more preferably −100 to 37 ° C., and still more preferably −80 to 0 ° C. When the Tg of the macroinitiator F2 is less than or equal to the upper limit of the above range, biological components such as proteins are not easily adsorbed to the present fluoropolymer. When the Tg of the macroinitiator F2 is equal to or higher than the lower limit of the above range, the macroinitiator has sufficient viscosity at room temperature and sufficient film strength.
　マクロ開始剤Ｆ２の具体例としては、Ｂｒ（ＣＨ２－ＣＨ（ＣＯＯＣＨ２ＣＦ３））ｎ－Ｃ（ＣＨ３）２－ＣＯＯ－ＣＨ２ＣＨ３、Ｂｒ（ＣＨ２－ＣＨ（ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３））ｎ－Ｃ（ＣＨ３）２－ＣＯＯ－ＣＨ２ＣＨ３を例示できる。なかでも、Ｂｒ（ＣＨ２－ＣＨ（ＣＯＯＣＨ２ＣＦ３））ｎ－Ｃ（ＣＨ３）２－ＣＯＯ－ＣＨ２ＣＨ３が好ましい。（ただし、ｎは１～５０である。） Specific examples of the macroinitiator F2 include Br (CH 2 —CH (COOCH 2 CF 3 )) n —C (CH 3 ) 2 —COO—CH 2 CH 3 and Br (CH 2 —CH (CF 2 CF 2) CF 2 CF 2 CF 2 CF 3 )) n —C (CH 3 ) 2 —COO—CH 2 CH 3 . Among them, Br (CH 2 —CH (COOCH 2 CF 3 )) n —C (CH 3 ) 2 —COO—CH 2 CH 3 is preferable. (However, n is 1 to 50.)
　単量体Ｆ３は、Ｒｆ基を有する含フッ素単量体である。ただし、単量体Ｆ３に基づく単位には、含フッ素マクロ開始剤を構成する含フッ素単量体に基づく単位は含まれない。
　単量体Ｆ３のＴｍは、３７℃以下が好ましく、－１００～３７℃がより好ましく、－８０～０℃がさらに好ましい。単量体Ｆ３のＴｍが前記範囲の上限値以下であれば、本含フッ素重合体にタンパク質等の生体成分が吸着しにくい。単量体Ｆ３のＴｍが前記範囲の下限値以上であれば、室温で充分な粘度を有し、充分な膜強度が得られる。 The monomer F3 is a fluorine-containing monomer having an Rf group. However, the unit based on the monomer F3 does not include the unit based on the fluorinated monomer constituting the fluorinated macroinitiator.
The Tm of the monomer F3 is preferably 37 ° C. or lower, more preferably −100 to 37 ° C., and still more preferably −80 to 0 ° C. When the Tm of the monomer F3 is equal to or less than the upper limit of the above range, biological components such as proteins are not easily adsorbed to the present fluoropolymer. When the Tm of the monomer F3 is equal to or more than the lower limit of the above range, the monomer F3 has a sufficient viscosity at room temperature and a sufficient film strength can be obtained.
　単量体Ｆ３としては、Ｒｆ基を有するポリフルオロアルキル（メタ）アクリレート、ポリフルオロエーテル（メタ）アクリレートを例示できる。なかでも、Ｒｆ基を有するポリフルオロアルキル（メタ）アクリレートが好ましく、以下の化合物Ｆ３１がより好ましい。 Examples of the monomer F3 include a polyfluoroalkyl (meth) acrylate and a polyfluoroether (meth) acrylate having an Rf group. Among them, a polyfluoroalkyl (meth) acrylate having an R f group is preferable, and the following compound F31 is more preferable.
Figure JPOXMLDOC01-appb-C000002
Figure JPOXMLDOC01-appb-C000002
　ただし、前記式Ｆ３１中のＲ１は、水素原子又はメチル基である。ｃ１は１～４であり、ｃ２は１～６である。
　ｃ１は、１～２が好ましい。
　ｃ２は、１～４が好ましく、１がより好ましい。 Here, R 1 in the above formula F31 is a hydrogen atom or a methyl group. c1 is 1 to 4, and c2 is 1 to 6.
c1 is preferably 1 to 2.
c2 is preferably from 1 to 4, and more preferably 1.
　化合物Ｆ３１の具体例としては、以下の化合物を例示できる。
　ＣＨ２＝ＣＨＣＯＯＣＨ２ＣＦ３、
　ＣＨ２＝Ｃ（ＣＨ３）ＣＯＯＣＨ２ＣＦ３、
　ＣＨ２＝ＣＨＣＯＯ（ＣＨ２）２（ＣＦ２）５－ＣＦ３、
　ＣＨ２＝Ｃ（ＣＨ３）ＣＯＯ（ＣＨ２）２（ＣＦ２）５－ＣＦ３等。 Specific examples of the compound F31 include the following compounds.
CH 2 ＣＨCHCOOCH 2 CF 3 ,
CH 2 ＣC (CH 3 ) COOCH 2 CF 3 ,
CH 2 ＣＨCHCOO (CH 2 ) 2 (CF 2 ) 5 —CF 3 ,
CH 2 ＣC (CH 3 ) COO (CH 2 ) 2 (CF 2 ) 5 —CF 3 and the like.
　化合物Ｆ３１としては、ＣＨ２＝ＣＨＣＯＯＣＨ２ＣＦ３、ＣＨ２＝Ｃ（ＣＨ３）ＣＯＯＣＨ２ＣＦ３、ＣＨ２＝ＣＨＣＯＯ（ＣＨ２）２（ＣＦ２）５－ＣＦ３、ＣＨ２＝Ｃ（ＣＨ３）ＣＯＯ（ＣＨ２）２（ＣＦ２）５－ＣＦ３が好ましく、ＣＨ２＝ＣＨＣＯＯＣＨ２ＣＦ３、ＣＨ２＝Ｃ（ＣＨ３）ＣＯＯＣＨ２ＣＦ３がより好ましい。
　本含フッ素重合体が有する単量体Ｆ３に基づく単位は、１種でもよく、２種以上でもよい。 The compound F31, CH 2 = CHCOOCH 2 CF 3, CH 2 = C (CH 3) COOCH 2 CF 3, CH 2 = CHCOO (CH 2) 2 (CF 2) 5 -CF 3, CH 2 = C (CH 3 ) COO (CH 2 ) 2 (CF 2 ) 5 —CF 3 is preferable, and CH 2 ＣＨCHCOOCH 2 CF 3 and CH 2 ＣC (CH 3 ) COOCH 2 CF 3 are more preferable.
The unit based on the monomer F3 of the present fluorine-containing polymer may be one type, or two or more types.
　マクロモノマーＦ４は、Ｒｆ基を有する含フッ素マクロモノマーである。
　マクロモノマーＦ４のＴｇは、３７℃以下が好ましく、－１００～３７℃がより好ましく、－８０～０℃がさらに好ましい。マクロモノマーＦ４のＴｇが前記範囲の上限値以下であれば、本含フッ素重合体にタンパク質等の生体成分が吸着しにくい。マクロモノマーＦ４のＴｇが前記範囲の下限値以上であれば、室温で充分な粘度を有し、充分な膜強度が得られる。 The macromonomer F4 is a fluorine-containing macromonomer having an Rf group.
The Tg of the macromonomer F4 is preferably 37 ° C. or lower, more preferably −100 to 37 ° C., and still more preferably −80 to 0 ° C. When the Tg of the macromonomer F4 is equal to or less than the upper limit of the above range, biological components such as proteins are not easily adsorbed to the present fluoropolymer. When the Tg of the macromonomer F4 is equal to or more than the lower limit of the above range, the macromonomer F4 has sufficient viscosity at room temperature and sufficient film strength can be obtained.
　マクロモノマーＦ４の具体例としては、ＣＨ２＝Ｃ（ＣＨ３）ＣＯＯ（ＣＨ２）２（ＣＨ２－ＣＨ（ＣＯＯＣＨ２ＣＦ３））nＨ、ＣＨ２＝ＣＨＣＯＯ（ＣＨ２）２（ＣＨ２－ＣＨ（ＣＯＯＣＨ２ＣＦ３））nＨ、ＣＨ２＝Ｃ（ＣＨ３）ＣＯＯ（ＣＨ２）２（ＣＨ２－ＣＨ（ＣＯＯＣＨ２ＣＨ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３））nＨ、ＣＨ２＝ＣＨＣＯＯ（ＣＨ２）２（ＣＨ２－ＣＨ（ＣＯＯＣＨ２ＣＨ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３））nＨを例示できる。なかでも、ＣＨ２＝ＣＨＣＯＯ（ＣＨ２）２（ＣＨ２－ＣＨ（ＣＯＯＣＨ２ＣＦ３））nＨ、ＣＨ２＝ＣＨＣＯＯ（ＣＨ２）２（ＣＨ２－ＣＨ（ＣＯＯＣＨ２ＣＨ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ３））nＨが好ましい。（ただし、ｎは１～５０である。） Specific examples of the macromonomer F4 include CH 2 ＣC (CH 3 ) COO (CH 2 ) 2 (CH 2 —CH (COOCH 2 CF 3 )) n H, CH 2 ＣＨCHCOO (CH 2 ) 2 (CH 2 —CH (COOCH 2 CF 3 )) n H, CH 2 ＣC (CH 3 ) COO (CH 2 ) 2 (CH 2 —CH (COOCH 2 CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3 )) n H, CH 2 = CHCOO ( CH 2) 2 (CH 2 -CH (COOCH 2 CH 2 CF 2 CF 2 CF 2 CF 2 CF 2 CF 3)) n H a can be exemplified. Among them, CH 2 ＣＨCHCOO (CH 2 ) 2 (CH 2 —CH (COOCH 2 CF 3 )) n H, CH 2 ＣＨCHCOO (CH 2 ) 2 (CH 2 —CH (COOCH 2 CH 2 CF 2 CF 2) CF 2 CF 2 CF 2 CF 3 )) n H is preferred. (However, n is 1 to 50.)
　本含フッ素重合体は、本発明の効果を損なわない範囲であれば、ＨＥＭＡ以外のフッ素原子を有しない非フッ素系単量体に基づく単位を有していてもよい。
　ＨＥＭＡ以外の非フッ素系単量体としては、メトキシエチルアクリレート（ＭＥＡ）、２－ヒドロキシアクリレート（ＨＥＡ）、ポリエチレングリコールアクリレート（ＰＥＧＡ）、テトラヒドロフルフリルアクリレート（ＴＨＦＡ）、メチルメタクリレート（ＭＭＡ）、ブチルメタクリレート（ＢＭＡ）、メトキシエチルメタクリレート（ＭＥＭＡ）を例示できる。 The present fluorine-containing polymer may have a unit based on a non-fluorine-based monomer having no fluorine atom other than HEMA as long as the effect of the present invention is not impaired.
Non-fluorinated monomers other than HEMA include methoxyethyl acrylate (MEA), 2-hydroxyacrylate (HEA), polyethylene glycol acrylate (PEGA), tetrahydrofurfuryl acrylate (THFA), methyl methacrylate (MMA), and butyl methacrylate (BMA) and methoxyethyl methacrylate (MEMA).
　本含フッ素重合体は、含フッ素部分Ｆとして、開始剤Ｆ１に基づく部分、マクロ開始剤Ｆ２に基づく部分、単量体Ｆ３に基づく単位、及びマクロモノマーＦ４に基づく単位のうちのいずれか１種のみを有していてもよく、これらのうちの２種以上を有していてもよい。 The present fluorinated polymer has, as the fluorinated moiety F, any one of a moiety based on the initiator F1, a moiety based on the macroinitiator F2, a unit based on the monomer F3, and a unit based on the macromonomer F4. May be included, or two or more of these may be included.
　本含フッ素重合体が含フッ素部分Ｆとして単量体Ｆ３に基づく単位又はマクロモノマーＦ４に基づく単位を有する場合、本含フッ素重合体は、ブロック共重合体であってもよく、ランダム共重合体であってもよい。
　本含フッ素重合体としては、含フッ素部分Ｆが単量体Ｆ３に基づく単位のみからなる含フッ素重合体が好ましく、ＨＥＭＡと単量体Ｆ３のランダム共重合体が特に好ましい。 When the fluorinated polymer has a unit based on the monomer F3 or a unit based on the macromonomer F4 as the fluorinated moiety F, the fluorinated polymer may be a block copolymer, and a random copolymer. It may be.
As the present fluorinated polymer, a fluorinated polymer in which the fluorinated moiety F consists only of a unit based on the monomer F3 is preferable, and a random copolymer of HEMA and the monomer F3 is particularly preferable.
　本含フッ素重合体中のＨＥＭＡ単位の含有量は、本含フッ素重合体の総質量に対して、５０質量％以上であり、５０～９９質量％が好ましく、７５～９９質量％がより好ましく、９０～９９質量％がさらに好ましい。ＨＥＭＡ単位の含有量が前記範囲内であれば、本含フッ素重合体にタンパク質等の生体成分が吸着しにくい。 The content of the HEMA unit in the present fluoropolymer is 50% by mass or more, preferably 50 to 99% by mass, more preferably 75 to 99% by mass, based on the total mass of the present fluoropolymer. 90 to 99% by mass is more preferred. When the content of the HEMA unit is within the above range, it is difficult for biological components such as proteins to be adsorbed to the present fluoropolymer.
　本含フッ素重合体中の含フッ素部分Ｆの含有量は、本含フッ素重合体の総質量に対して、０．１～１６質量％であり、０．５～１５質量％が好ましく、１．０～１５質量％がより好ましい。含フッ素部分Ｆの含有量が前記範囲内であれば、本含フッ素重合体にタンパク質等の生体成分が吸着しにくい。 The content of the fluorinated moiety F in the present fluorinated polymer is 0.1 to 16% by mass, preferably 0.5 to 15% by mass, based on the total mass of the fluorinated polymer. 0 to 15% by mass is more preferred. When the content of the fluorinated moiety F is within the above range, biological components such as proteins are not easily adsorbed to the fluorinated polymer.
　本含フッ素重合体中の含フッ素部分Ｆ及びＨＥＭＡ単位の合計の含有量は、本含フッ素重合体の総質量に対して、５０．１質量％以上が好ましく、７５質量％以上がより好ましく、１００質量％が特に好ましい。 The total content of the fluorine-containing moiety F and the HEMA unit in the present fluorine-containing polymer is preferably 50.1% by mass or more, more preferably 75% by mass or more, based on the total mass of the present fluorine-containing polymer. 100% by weight is particularly preferred.
　本含フッ素重合体の数平均分子量（Ｍｎ）は、５０００～５０００００が好ましく、５０００～２０００００がより好ましい。本含フッ素重合体のＭｎが前記範囲の下限値以上であれば、耐水性の低い低分子量成分の溶出が抑えられる。本含フッ素重合体のＭｎが前記範囲の上限値以下であれば、粘度が上がり分子の運動性が低下し、水と相互作用しにくくなる可能性が低い。 数 The number average molecular weight (Mn) of the fluoropolymer is preferably from 5,000 to 500,000, more preferably from 5,000 to 200,000. When the Mn of the present fluorine-containing polymer is at least the lower limit of the above range, elution of low molecular weight components having low water resistance can be suppressed. When the Mn of the present fluoropolymer is equal to or less than the upper limit of the above range, the viscosity is increased, the mobility of the molecule is reduced, and the possibility of difficulty in interacting with water is low.
　本含フッ素重合体の重量平均分子量（Ｍｗ）は、５０００～５０００００が好ましく、５０００～２０００００がより好ましい。本含フッ素重合体のＭｗが前記範囲の下限値以上であれば、耐水性の低い低分子量成分の溶出が抑えられる。本含フッ素重合体のＭｗが前記範囲の上限値以下であれば、粘度が上がり分子の運動性が低下し、水と相互作用しにくくなる可能性が低い。 重量 The weight average molecular weight (Mw) of the fluoropolymer is preferably from 5,000 to 500,000, more preferably from 5,000 to 200,000. When the Mw of the present fluoropolymer is at least the lower limit of the above range, elution of low molecular weight components having low water resistance can be suppressed. When the Mw of the present fluoropolymer is equal to or less than the upper limit of the above range, the viscosity is increased, the mobility of the molecule is reduced, and the possibility that the molecule does not easily interact with water is low.
　本含フッ素重合体の分子量分布（Ｍｗ／Ｍｎ）は、１．０～３．０が好ましく、１．０～２．５がより好ましい。本含フッ素重合体のＭｗ／Ｍｎが前記範囲の上限値以下であれば、ロット間ばらつきを最小限に抑えることができる。 分子 The molecular weight distribution (Mw / Mn) of the present fluoropolymer is preferably from 1.0 to 3.0, more preferably from 1.0 to 2.5. When Mw / Mn of the present fluoropolymer is equal to or less than the upper limit of the above range, lot-to-lot variation can be minimized.
　本含フッ素重合体のＤＳＣ法で測定される中間水量は、０．５質量％以上が好ましく、５質量％以上がより好ましい。本含フッ素重合体の中間水量が前記下限値以上であれば、タンパク質等の生体成分が吸着しにくくなる。本含フッ素重合体の中間水量は、多ければ多いほど良く、実質的には１０質量％以下である。 中間 The amount of intermediate water of the fluoropolymer measured by the DSC method is preferably 0.5% by mass or more, more preferably 5% by mass or more. When the amount of intermediate water of the present fluorinated polymer is not less than the lower limit, biological components such as proteins are less likely to be adsorbed. The larger the amount of intermediate water in the present fluoropolymer, the better, and it is substantially 10% by mass or less.
　本含フッ素重合体の製造方法は、特に限定されない。
　例えば、開始剤Ｆ１やマクロ開始剤Ｆ２を用いる場合、開始剤Ｆ１及びマクロ開始剤Ｆ２の少なくとも一方、ＨＥＭＡ、及び必要に応じて使用する単量体Ｆ３、マクロモノマーＦ４等を重合溶媒に加え、開始剤Ｆ１やマクロ開始剤Ｆ２から生じるラジカル部を起点にしたＡＴＲＰを行う方法を例示できる。ＡＴＲＰは、脱酸素環境下で行うことが好ましい。開始剤Ｆ１及びマクロ開始剤Ｆ２を用いない場合は、重合開始剤としてアゾ化合物（２，２－アゾビスイソブチロニトリル等）や有機過酸化物（イソブチリルペルオキシド等）、ＨＥＭＡ、単量体Ｆ３及びマクロモノマーＦ４の少なくとも一方を重合溶媒に加え、ラジカル重合する方法を例示できる。 The method for producing the present fluoropolymer is not particularly limited.
For example, when the initiator F1 or the macroinitiator F2 is used, at least one of the initiator F1 and the macroinitiator F2, HEMA, and a monomer F3, a macromonomer F4 and the like used as needed are added to the polymerization solvent, A method of performing ATRP starting from a radical portion generated from the initiator F1 or the macroinitiator F2 can be exemplified. ATRP is preferably performed in a deoxygenated environment. When the initiator F1 and the macroinitiator F2 are not used, azo compounds (2,2-azobisisobutyronitrile and the like), organic peroxides (isobutyryl peroxide and the like), HEMA, monomer A method in which at least one of the body F3 and the macromonomer F4 is added to a polymerization solvent and radical polymerization is performed can be exemplified.
　重合溶媒としては、特に限定されず、ケトン（アセトン、メチルエチルケトン、メチルイソブチルケトン等）、アルコール（メタノール、２－プロピルアルコール等）、エステル（酢酸エチル、酢酸ブチル等）、エーテル（ジイソプロピルエーテル、テトラヒドロフラン、ジオキサン等）、グリコールエーテル（エチレングリコール、プロピレングリコール、ジプロピレングリコールのエチルエーテル又はメチルエーテル等）及びその誘導体、脂肪族炭化水素、芳香族炭化水素、ハロゲン化炭化水素（パークロロエチレン、トリクロロ－１，１，１－エタン、トリクロロトリフルオロエタン、ジクロロペンタフルオロプロパン等）、Ｎ，Ｎ－ジメチルホルムアミド、Ｎ－メチル－２－ピロリドン、ブチロアセトン、ジメチルスルホキシド（ＤＭＳＯ）等が挙げられる。 The polymerization solvent is not particularly limited and includes ketones (acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), alcohols (methanol, 2-propyl alcohol, etc.), esters (ethyl acetate, butyl acetate, etc.), ethers (diisopropyl ether, tetrahydrofuran, Dioxane), glycol ethers (such as ethyl ether or methyl ether of ethylene glycol, propylene glycol, and dipropylene glycol) and derivatives thereof, aliphatic hydrocarbons, aromatic hydrocarbons, and halogenated hydrocarbons (perchloroethylene, trichloro-1). , 1,1-ethane, trichlorotrifluoroethane, dichloropentafluoropropane, etc.), N, N-dimethylformamide, N-methyl-2-pyrrolidone, butylacetone, dimethylsulfoxide ( MSO), and the like.
　本含フッ素重合体を得る重合反応における反応液中の単量体及び含フッ素マクロモノマーの合計濃度は、５～５０質量％が好ましく、１０～３０質量％が特に好ましい。
　反応液中の重合開始剤及び含フッ素マクロ開始剤の合計量は、単量体及び含フッ素マクロモノマーの合計量１００質量部に対して、０．１～３質量部が好ましく、０．５～１．０質量部がより好ましい。
　重合温度は、５０～１００℃が好ましく、６０～９０℃がより好ましい。 The total concentration of the monomer and the fluorinated macromonomer in the reaction solution in the polymerization reaction for obtaining the present fluorinated polymer is preferably from 5 to 50% by mass, particularly preferably from 10 to 30% by mass.
The total amount of the polymerization initiator and the fluorinated macroinitiator in the reaction solution is preferably 0.1 to 3 parts by mass, preferably 0.5 to 3 parts by mass, based on 100 parts by mass of the total amount of the monomer and the fluorinated macromonomer. 1.0 parts by mass is more preferred.
The polymerization temperature is preferably from 50 to 100 ° C, more preferably from 60 to 90 ° C.
［膜］
　本発明の膜は、本含フッ素重合体を含む膜である。本発明の膜は、本発明の効果を損なわない範囲であれば、本含フッ素重合体以外の他の成分を含んでもよい。他の成分としては、レベリング剤、熱可塑性樹脂、熱硬化性樹脂、光硬化性樹脂、紫外線吸収剤、抗菌剤を例示できる。
　本発明の膜中の本含フッ素重合体の含有量は、膜の総質量に対して、０．１質量％以上が好ましく、０．５質量％以上がより好ましく、１．０質量％以上がさらに好ましい。 [film]
The film of the present invention is a film containing the present fluoropolymer. The film of the present invention may contain components other than the present fluoropolymer as long as the effects of the present invention are not impaired. Examples of other components include a leveling agent, a thermoplastic resin, a thermosetting resin, a photocurable resin, an ultraviolet absorber, and an antibacterial agent.
The content of the present fluoropolymer in the film of the present invention is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and preferably 1.0% by mass or more based on the total mass of the film. More preferred.
　本発明の膜の水中における膜表面の気泡接触角は、１３５°以上が好ましく、１４０°以上がより好ましく、１５０°以上がさらに好ましい。膜表面の気泡接触角が前記下限値以上であれば、膜にタンパク質等の生体成分が吸着しにくい。膜表面の気泡接触角は、大きければ大きいほど良い。 気 泡 The bubble contact angle of the film surface of the film of the present invention in water is preferably 135 ° or more, more preferably 140 ° or more, even more preferably 150 ° or more. When the bubble contact angle on the membrane surface is equal to or larger than the lower limit, biological components such as proteins are not easily adsorbed on the membrane. The larger the bubble contact angle on the film surface, the better.
　特に、中間水量が０．１質量％以上、５質量％未満の本含フッ素重合体を用いて膜を形成する場合、水中における膜表面の気泡接触角が１３５°以上という条件を満たすことが好ましい。これにより、本含フッ素重合体の中間水量が低くても、膜にタンパク質等の生体成分が吸着しにくくなる。 In particular, when a film is formed using the present fluorine-containing polymer having an intermediate water content of 0.1% by mass or more and less than 5% by mass, it is preferable to satisfy the condition that the bubble contact angle of the film surface in water is 135 ° or more. . This makes it difficult for biological components such as proteins to be adsorbed to the membrane even when the amount of intermediate water of the present fluoropolymer is low.
　本発明の膜の厚さは、０．０１～１００μｍが好ましく、０．１～１０μｍがより好ましい。膜の厚さが前記範囲の下限値以上であれば、連続膜として機能し、十分な膜強度を得られる。膜の厚さが前記範囲の上限値以下であれば、材料の利用効率が高い。 膜 The thickness of the film of the present invention is preferably 0.01 to 100 μm, more preferably 0.1 to 10 μm. When the thickness of the film is equal to or more than the lower limit of the above range, the film functions as a continuous film, and sufficient film strength can be obtained. When the thickness of the film is equal to or less than the upper limit of the above range, the utilization efficiency of the material is high.
　膜の製造方法は、特に限定されない。例えば、本含フッ素重合体を含む塗布液を基材表面に塗布し、乾燥して膜を形成する方法を例示できる。
　塗布液に用いる溶媒としては、特に限定されず、エタノール、メタノール、アセトン、クロロホルム、テトラヒドロフラン、トルエン、キシレン、トリフルオロエタノール、ヘキサフルオロイソプロパノール、メトキシプロパノール、ジメチルホルムアミドを例示できる。 The method for producing the film is not particularly limited. For example, a method in which a coating solution containing the present fluoropolymer is applied to the surface of a substrate and dried to form a film can be exemplified.
The solvent used for the coating solution is not particularly limited, and examples thereof include ethanol, methanol, acetone, chloroform, tetrahydrofuran, toluene, xylene, trifluoroethanol, hexafluoroisopropanol, methoxypropanol, and dimethylformamide.
　塗布液中の本含フッ素重合体の濃度は、０．０１～５．０質量％が好ましく、０．１～３．０％がより好ましい。本含フッ素重合体の濃度が前記範囲内であれば、均一に塗布できるため、均一な膜を形成しやすい。 (4) The concentration of the present fluoropolymer in the coating solution is preferably 0.01 to 5.0% by mass, more preferably 0.1 to 3.0%. If the concentration of the present fluoropolymer is within the above range, it can be applied uniformly, so that a uniform film is easily formed.
［医療用具］
　本発明の医療用具は、基材と、基材上の少なくとも一部に形成された本発明の膜とを有する。本発明の医療用具では、基材上の一部の領域に膜が限定的に形成されていてもよく、基材上に全体的に膜が形成されていてもよい。
　本発明の医療用具は、基材と膜の間に中間層を有していてもよい。中間層としては、ポリメタクリルメチルアクリレート（ＰＭＭＡ）を例示できる。 [Medical tools]
The medical device of the present invention has a substrate and the film of the present invention formed on at least a part of the substrate. In the medical device of the present invention, a film may be limitedly formed in a partial region on the substrate, or the film may be entirely formed on the substrate.
The medical device of the present invention may have an intermediate layer between the substrate and the membrane. Examples of the intermediate layer include polymethacrylmethyl acrylate (PMMA).
　医療用具とは、治療、診断、解剖学的又は生物学的な検査等の医療用として用いられる器具を指し、人体等の生体内に挿入あるいは接触させる、又は生体から取り出した成分（血液等）と接触させる如何なる器具をも含む。 The medical device refers to a device used for medical treatment, such as treatment, diagnosis, anatomical or biological examination, and is inserted or brought into contact with a living body such as a human body, or a component (blood or the like) removed from the living body. And any device that is brought into contact with.
　本発明の医療用具の基材としては、細胞培養容器、細胞培養シート、細胞捕捉フィルター、バイアル、プラスチックコートバイアル、シリンジ、プラスチックコートシリンジ、アンプル、プラスチックコートアンプル、カートリッジ、ボトル、プラスチックコートボトル、パウチ、ポンプ、噴霧器、栓、プランジャー、キャップ、蓋、針、ステント、カテーテル、インプラント、コンタクトレンズ、マイクロ流路チップ、ドラッグデリバリーシステム材、人工血管、人工臓器、血液透析膜、ガードワイヤー、血液フィルター、血液保存パック、内視鏡、バイオチップ、糖鎖合成機器、成形補助材、包装材を例示できる。
　基材を形成する材料としては、特に限定されず、ポリスチレン、ポリカーボネート、ポリプロピレン等の樹脂、ガラスを例示できる。 The base material of the medical device of the present invention includes a cell culture container, a cell culture sheet, a cell capture filter, a vial, a plastic coated vial, a syringe, a plastic coated syringe, an ampoule, a plastic coated ampule, a cartridge, a bottle, a plastic coated bottle, and a pouch. , Pumps, nebulizers, stoppers, plungers, caps, lids, needles, stents, catheters, implants, contact lenses, microchannel chips, drug delivery system materials, artificial blood vessels, artificial organs, hemodialysis membranes, guard wires, blood filters , A blood storage pack, an endoscope, a biochip, a sugar chain synthesis device, a molding auxiliary material, and a packaging material.
The material for forming the substrate is not particularly limited, and examples thereof include resins such as polystyrene, polycarbonate, and polypropylene, and glass.
　以上説明したように、本発明においては、ＨＥＭＡ単位を主成分とし、かつＲｆ基を有する含フッ素部分Ｆを特定の比率で有する含フッ素重合体とする。これにより、優れた生体親和性が得られ、タンパク質等の生体成分が吸着することが抑制される。そのため、本含フッ素重合体は、繰り返し使用したり、長時間使用したりする医療用具への適用においても有用である。
　また、本含フッ素重合体は、含フッ素部分Ｆを有するため、非特許文献１のようにアミノ基を導入する従来の重合体に比べて、耐水性にも優れる。 As described above, in the present invention, a fluorine-containing polymer having a HEMA unit as a main component and a fluorine-containing moiety F having an Rf group at a specific ratio is used. Thereby, excellent biocompatibility is obtained, and adsorption of biocomponents such as proteins is suppressed. Therefore, the present fluoropolymer is also useful for application to medical devices that are used repeatedly or used for a long time.
Further, since the present fluorinated polymer has a fluorinated portion F, it is excellent in water resistance as compared with a conventional polymer in which an amino group is introduced as in Non-Patent Document 1.
　本含フッ素重合体において生体親和性が向上する要因は、以下のように考えられる。
　含水した重合体に含まれる水には、一般に自由水、中間水、不凍水が存在し、中間水量が多いほど、生体親和性に優れ、タンパク質等の生体成分が吸着しにくくなることが知られている（M. Tanaka et al., Polym. J, 2013, 45, 701）。本含フッ素重合体では、含フッ素部分Ｆが特定の比率で含まれているため、含水させた際の重合体の水和構造が変わり、自由水が減少して中間水が増加していると考えられる。また、本含フッ素重合体の含フッ素部分Ｆが有するＲｆ基は、非特許文献２のＣＦ３（ＣＦ２）７（ＣＨ２）２－に比べて短く、結晶性が低いため、本含フッ素重合体中の中間水と相互作用する部分が表面に効率的に配向しやすくなると考えられる。これらのことから、生体親和性に優れたものとなり、タンパク質等の生体成分の吸着抑制効果が高くなると考えられる。 The factors that improve the biocompatibility of the present fluoropolymer are considered as follows.
Generally, free water, intermediate water, and antifreeze water are present in the water contained in the water-containing polymer. It is known that the greater the amount of intermediate water, the better the biocompatibility and the less likely it is for biological components such as proteins to be adsorbed. (M. Tanaka et al., Polym. J, 2013, 45, 701). In the present fluorinated polymer, since the fluorinated portion F is contained at a specific ratio, the hydration structure of the polymer when hydrated changes, and the free water decreases and the intermediate water increases. Conceivable. Further, the R f group contained in the fluorinated portion F of the present fluorinated polymer is shorter than CF 3 (CF 2 ) 7 (CH 2 ) 2 -in Non-Patent Document 2, and has low crystallinity. It is considered that the portion of the fluoropolymer that interacts with the intermediate water is likely to be efficiently oriented on the surface. From these facts, it is considered that the composition has excellent biocompatibility and the effect of suppressing adsorption of biological components such as proteins is enhanced.
　また、膜において、水中における膜表面の気泡接触角が１３５°以上という条件を満たされると、本含フッ素重合体中の中間水と相互作用する部分がより効率的に膜表面に配向しやすくなり、タンパク質等の生体成分の吸着抑制効果がさらに高くなる。 Also, in the membrane, when the condition that the bubble contact angle of the membrane surface in water is 135 ° or more is satisfied, the portion interacting with the intermediate water in the present fluoropolymer is more easily oriented on the membrane surface. In addition, the effect of suppressing adsorption of biological components such as proteins is further enhanced.
　以下、実施例によって本発明を具体的に説明するが、本発明は以下の記載によっては限定されない。
［数平均分子量（Ｍｎ）、重量平均分子量（Ｍｗ）、分子量分布（Ｍｗ／Ｍｎ）］
　重合体の数平均分子量（Ｍｎ）及び重量平均分子量（Ｍｗ）は、テトラヒドロフラン（ＴＨＦ）を溶離液として用いるゲル浸透クロマトグラフィー（ＧＰＣ）測定により、ポリスチレン換算分子量として求めた。測定は、東ソー社製のＧＰＣ（製品名「ＨＬＣ－８２２０」）を用いて、温度４０℃、流量１．０ｍＬ／分の条件で行った。カラム構成は、東ソー社製のSuper HZ4000、Super HZ3000、Super HZ2500、Super HZ2000を直列に接続する構成とした。
　分子量分布（Ｍｗ／Ｍｎ）は、ＧＰＣ測定により求められたＭｗとＭｎを用いて算出した。 Hereinafter, the present invention will be described specifically with reference to examples, but the present invention is not limited by the following description.
[Number average molecular weight (Mn), weight average molecular weight (Mw), molecular weight distribution (Mw / Mn)]
The number average molecular weight (Mn) and the weight average molecular weight (Mw) of the polymer were determined by gel permeation chromatography (GPC) using tetrahydrofuran (THF) as an eluent as polystyrene equivalent molecular weight. The measurement was performed using GPC (product name “HLC-8220”) manufactured by Tosoh Corporation at a temperature of 40 ° C. and a flow rate of 1.0 mL / min. The column configuration was such that Tosoh Super HZ4000, Super HZ3000, Super HZ2500, and Super HZ2000 were connected in series.
The molecular weight distribution (Mw / Mn) was calculated using Mw and Mn determined by GPC measurement.
［重合体の組成］
　各例で得た重合体の組成は、１Ｈ　ＮＭＲ（ＪＥＯＬ社製）の分析結果から算出した。ＮＭＲ分析は、溶媒として重ＤＭＳＯ（ＤＭＳＯ－ｄ６）を用い、室温（２５℃）で行った。 [Polymer composition]
The composition of the polymer obtained in each example was calculated from the analysis result of 1 H NMR (manufactured by JEOL). NMR analysis was performed at room temperature (25 ° C.) using heavy DMSO (DMSO-d6) as a solvent.
［中間水量］
　各例で得た重合体を水中に浸漬して含水させた後、所定量を採取して試料とし、あらかじめ質量を測定したアルミパンの底に薄く広げた。示差走査熱量計（ＴＡ　インスツルメント社製、製品名「Ｑ２０」）を用い、５℃／分の条件で、（ｉ）３０℃から５０℃まで加熱、（ｉｉ）３０℃から－８０℃まで冷却、（ｉｉｉ）－８０℃から５０℃まで加熱を行った。この温度プログラムでのＤＳＣ昇温カーブを取得し、吸発熱量を測定した。ＤＳＣ測定後にアルミパンにピンホールをあけて試料を真空乾燥させて質量を測定し、乾燥前後の試料の質量から含水量を求め、下式１から試料の含水率（ＷＣ）を算出した。
　ＷＣ＝（（Ｗ１－Ｗ０）／Ｗ１）×１００　式１
（ただし、前記式１中、ＷＣは試料の含水率（質量％）であり、Ｗ０は乾燥後の試料の質量（ｇ）であり、Ｗ１は乾燥前の試料の質量（ｇ）である。） [Intermediate water volume]
After the polymer obtained in each example was immersed in water to be hydrated, a predetermined amount was taken as a sample and spread thinly on the bottom of an aluminum pan whose mass was measured in advance. Using a differential scanning calorimeter (manufactured by TA Instruments, product name "Q20"), at 5 ° C / min, (i) heating from 30 ° C to 50 ° C, (ii) from 30 ° C to -80 ° C Cooling and (iii) heating from -80 ° C to 50 ° C. The DSC temperature rise curve was obtained by this temperature program, and the amount of heat absorption and heat generation was measured. After the DSC measurement, a pinhole was opened in an aluminum pan and the sample was vacuum-dried, the mass was measured, the water content was determined from the mass of the sample before and after drying, and the water content (W C ) of the sample was calculated from the following equation 1.
W C = ((W 1 −W 0 ) / W 1 ) × 100 Equation 1
(Where, in the above formula 1, W C is the moisture content (% by mass) of the sample, W 0 is the mass (g) of the sample after drying, and W 1 is the mass (g) of the sample before drying. is there.)
　試料の含水率と、ＤＳＣ昇温カーブにおける－１０℃～０℃付近の吸熱量から、試料に含まれる中間水の質量Ｗ２を求め、下式２から中間水量（ＷＩ）を算出した。
　ＷＩ＝（Ｗ２／Ｗ０）×１００　式２
（ただし、前記式２中、ＷＩは中間水量（質量％）であり、Ｗ０は乾燥後の試料の質量（ｇ）であり、Ｗ２は試料に含まれる中間水の質量（ｇ）である。） From the water content of the sample and the endothermic amount in the vicinity of −10 ° C. to 0 ° C. in the DSC heating curve, the mass W 2 of the intermediate water contained in the sample was obtained, and the amount of intermediate water (W I ) was calculated from the following equation 2.
W I = (W 2 / W 0 ) × 100 Equation 2
(Wherein, in the above formula 2, W I is the amount of intermediate water (% by mass), W 0 is the mass (g) of the dried sample, and W 2 is the mass (g) of the intermediate water contained in the sample. is there.)
［親水化速度］
　溶媒１ｍＬに対して、各例で得た重合体の０．２ｇを溶解して試料液とした。溶媒としては、メタノール又はＴＨＦを用いた。円板状のポリエチレンテレフタレート（ＰＥＴ）基板（１４ｍｍφ）をメタノールで前洗浄した。洗浄後のＰＥＴ基板の表面に、スピンコーターにて試料液を２度塗布し、乾燥して厚さ０．０５μｍの膜を形成した。２度の試料液の塗布の間隔は１５分とした。
　ＰＥＴ基板上に形成した膜表面の中心部、左端、右端の３点において、それぞれ水を滴下して接触角（°）を測定し、それらを平均して水接触角（°）とした。１点の測定につき２μＬの水滴を使用した。水の滴下から１秒後の水接触角θＡと１０秒後の水接触角θＢをそれぞれ測定し、ＶＨ＝（θＡ－θＢ）／９から親水化速度ＶＨ（°／秒）を算出した。 [Hydrophilic rate]
0.2 g of the polymer obtained in each example was dissolved in 1 mL of the solvent to prepare a sample solution. As a solvent, methanol or THF was used. A disk-shaped polyethylene terephthalate (PET) substrate (14 mmφ) was pre-washed with methanol. The sample liquid was applied twice on the surface of the washed PET substrate using a spin coater and dried to form a film having a thickness of 0.05 μm. The interval between two application of the sample liquid was 15 minutes.
At three points, that is, the center, the left end, and the right end of the surface of the film formed on the PET substrate, the contact angle (°) was measured by dropping water, and the average was defined as the water contact angle (°). 2 μL water droplets were used for one point measurement. Water dripping from the water contact angle theta A and 10 seconds after one second water contact angle theta B were respectively measured, V H = (θ A -θ B) / 9 from hydrophilization speed V H (° / sec ) Was calculated.
［気泡接触角］
　親水化速度の測定の手法と同様にしてＰＥＴ基板上に膜を形成した。膜を形成したＰＥＴ基板を１６時間水に浸漬した後、膜表面の中心部、左端、右端の３点において、水中で気泡の接触角（°）を測定し、それらを平均して気泡接触角（°）とした。１点の測定につき、２μＬの気泡を使用した。 [Bubble contact angle]
A film was formed on a PET substrate in the same manner as in the method of measuring the rate of hydrophilicity. After immersing the PET substrate on which the film was formed in water for 16 hours, the contact angles (°) of bubbles were measured in water at the center, left end, and right end of the film surface, and the averaged values were measured. (°). 2 μL of bubbles were used per measurement.
［タンパク質吸着試験］
　各例で得た重合体について、以下の方法によりタンパク質の吸着量を測定して評価した。
　親水化速度の測定と同様にして調製した試料液を、ポリプロピレン（ＰＰ）製の９６ウェルプレートのウェルに１５．０μＬ滴下した。次いで、ウェルに蓋をして、溶媒の蒸発速度を抑制しつつ３７℃の恒温槽で３日間静置して乾燥し、ウェルの底面に膜を形成した。膜を形成したウェルに、１ｍｇ／ｍＬに調整したヒトフィブリノーゲン（ｈＦｂｎ）溶液を５０μＬずつ加え、３７℃で１０分間保温した後、リン酸緩衝液（ＰＢＳ）を用いてウェルを洗浄した。次いで、０．５％ドデシル硫酸ナトリウム（ＳＤＳ）を含む１ＮＮａＯＨ水溶液の３０μＬをウェル内に加え、３７℃で２時間保温し、ウェル内の膜に吸着したタンパク質を水相に回収した。次いで、ウェル内にマイクロＢＣＡ試薬（サーモサイエンティフィック社製）を１５０μＬ、リン酸緩衝液ＰＢＳ（和光純薬社製）を１２０μＬ加えて３７℃で２時間保温し、十分に発色したことを確認した。ウェル内の溶液２００μＬを９６ウェルＴＣＰＳプレートに移し、マイクロプレートリーダーにて５６０ｎｍの光の吸光度を測定した。濃度が既知のタンパク質溶液による吸光度測定で作成した検量線を用いて、膜の単位面積あたりのタンパク質の吸着量を求めた。
　評価は、タンパク質の吸着量が０．６５μｇ／ｃｍ２以下を「〇（良好）」、０．６５μｇ／ｃｍ２超を「×（不良）」とした。 [Protein adsorption test]
The polymer obtained in each example was evaluated by measuring the amount of protein adsorbed by the following method.
15.0 μL of a sample solution prepared in the same manner as in the measurement of the hydrophilization rate was dropped into a well of a 96-well plate made of polypropylene (PP). Next, the well was capped and allowed to stand in a thermostat at 37 ° C. for 3 days while drying while suppressing the evaporation rate of the solvent, and dried to form a film on the bottom surface of the well. 50 μL of a human fibrinogen (hFbn) solution adjusted to 1 mg / mL was added to the wells on which the membrane was formed, and the mixture was incubated at 37 ° C. for 10 minutes, and then washed with a phosphate buffer solution (PBS). Next, 30 μL of a 1N NaOH aqueous solution containing 0.5% sodium dodecyl sulfate (SDS) was added into the well, and the mixture was kept at 37 ° C. for 2 hours, and the protein adsorbed on the membrane in the well was collected in the aqueous phase. Next, 150 μL of micro BCA reagent (manufactured by Thermo Scientific) and 120 μL of phosphate buffer PBS (manufactured by Wako Pure Chemical Industries) were added to the wells, and the mixture was kept at 37 ° C. for 2 hours to confirm that the color was sufficiently developed. did. 200 μL of the solution in the well was transferred to a 96-well TCPS plate, and the absorbance of light at 560 nm was measured using a microplate reader. The amount of protein adsorbed per unit area of the membrane was determined using a calibration curve created by absorbance measurement using a protein solution of known concentration.
Evaluation of the adsorbed amount of protein is 0.65μg / cm 2 or less "〇 (good)", a 0.65μg / cm 2 greater was evaluated as "× (poor)".
［原料］
　使用した原料の略号を以下に示す。
　ＨＥＭＡ：２－ヒドロキシエチルメタクリレート。
　３ＦＭ：２，２，２－トリフルオロエチルメタクリレート。
　ＡＩＢＮ：２，２－アゾビスイソブチロニトリル。
　ＤＭＦ：Ｎ，Ｎ－ジメチルホルムアミド。 [material]
Abbreviations of the used raw materials are shown below.
HEMA: 2-hydroxyethyl methacrylate.
3FM: 2,2,2-trifluoroethyl methacrylate.
AIBN: 2,2-azobisisobutyronitrile.
DMF: N, N-dimethylformamide.
［実施例１］
　撹拌装置、温度計、ジムロート冷却管、及び窒素導入管を取り付けた四つ口フラスコに、ＨＥＭＡの１．８９ｇ、３ＦＭの０．０７６ｇ、ＡＩＢＮの０．０２ｇ、ＤＭＦの９．７９ｍＬを仕込み、室温（２５℃）で溶解した。８０℃まで加熱し、８０℃で２０時間撹拌後、室温まで冷却した。得られた反応混合物を、ジエチルエーテル５００ｍＬに加えて沈殿させた。デカンテーションにより上層の溶液を除去した後、沈殿物をエタノール６０ｍＬに溶解し、エタノール溶液をジエチルエーテル５００ｍＬに加えて再沈殿し、沈殿物を回収した。回収物を一昼夜、減圧乾燥し、ＨＥＭＡと３ＦＭのランダム共重合体である含フッ素重合体Ｐ－１の１．７６ｇを得た。
　含フッ素重合体Ｐ－１のＭｎは２００００であり、Ｍｗは４１０００であり、Ｍｗ／Ｍｎは３．２であった。含フッ素重合体Ｐ－１の含フッ素部分の含有量は３．８質量％であった。 [Example 1]
1.89 g of HEMA, 0.076 g of 3FM, 0.02 g of AIBN, and 9.79 mL of DMF were charged into a four-necked flask equipped with a stirrer, thermometer, Dimroth condenser, and nitrogen inlet tube. (25 ° C.). The mixture was heated to 80 ° C., stirred at 80 ° C. for 20 hours, and then cooled to room temperature. The obtained reaction mixture was added to 500 mL of diethyl ether to cause precipitation. After removing the upper layer solution by decantation, the precipitate was dissolved in 60 mL of ethanol, and the ethanol solution was added to 500 mL of diethyl ether for reprecipitation, and the precipitate was recovered. The collected product was dried under reduced pressure for 24 hours to obtain 1.76 g of a fluoropolymer P-1 which was a random copolymer of HEMA and 3FM.
Mn of the fluoropolymer P-1 was 20,000, Mw was 41,000, and Mw / Mn was 3.2. The content of the fluorinated moiety in the fluorinated polymer P-1 was 3.8% by mass.
［実施例２］
　ＨＥＭＡの仕込み量を１．７３ｇ、３ＦＭの仕込み量を０．１１ｇに変更した以外は、実施例１と同様の手法で、ＨＥＭＡと３ＦＭのランダム共重合体である含フッ素重合体Ｐ－２の１．８６ｇを得た。
　含フッ素重合体Ｐ－２のＭｎは２００００であり、Ｍｗは４１０００であり、Ｍｗ／Ｍｎは３．２であった。含フッ素重合体Ｐ－２の含フッ素部分の含有量は６．４質量％であった。 [Example 2]
Except that the charged amount of HEMA was changed to 1.73 g and the charged amount of 3FM to 0.11 g, the same procedure as in Example 1 was used to prepare a fluoropolymer P-2 which is a random copolymer of HEMA and 3FM. 1.86 g were obtained.
Mn of the fluoropolymer P-2 was 20,000, Mw was 41,000, and Mw / Mn was 3.2. The content of the fluorinated moiety in the fluorinated polymer P-2 was 6.4% by mass.
［実施例３］
　ＨＥＭＡの仕込み量を１．６４ｇ、３ＦＭの仕込み量を０．２１ｇに変更した以外は、実施例１と同様の手法で、ＨＥＭＡと３ＦＭのランダム共重合体である含フッ素重合体Ｐ－３の１．７７ｇを得た。
　含フッ素重合体Ｐ－３のＭｎは２００００であり、Ｍｗは４１０００であり、Ｍｗ／Ｍｎは３．２であった。含フッ素重合体Ｐ－３の含フッ素部分の含有量は１２．６質量％であった。 [Example 3]
Except that the charged amount of HEMA was changed to 1.64 g, and the charged amount of 3FM was changed to 0.21 g, the same procedure as in Example 1 was used to prepare the fluoropolymer P-3 which is a random copolymer of HEMA and 3FM. 1.77 g were obtained.
Mn of the fluoropolymer P-3 was 20,000, Mw was 41,000, and Mw / Mn was 3.2. The content of the fluorinated moiety in the fluorinated polymer P-3 was 12.6% by mass.
［比較例１］
　３ＦＭを使用しなかった以外は、実施例１と同様の手法で、ＨＥＭＡの単独重合体である重合体Ｐ－４の１．５５ｇを得た。
　重合体Ｐ－４のＭｎは２００００であり、Ｍｗは４１０００であり、Ｍｗ／Ｍｎは３．２であった。 [Comparative Example 1]
In the same manner as in Example 1 except that 3FM was not used, 1.55 g of a polymer P-4 which was a homopolymer of HEMA was obtained.
Mn of the polymer P-4 was 20,000, Mw was 41,000, and Mw / Mn was 3.2.
［比較例２］
　ＨＥＭＡの仕込み量を０．９１ｇ、３ＦＭの仕込み量を１．０７ｇに変更した以外は、実施例１と同様の手法で、ＨＥＭＡと３ＦＭのランダム共重合体である含フッ素重合体Ｐ－５の１．４６ｇを得た。
　含フッ素重合体Ｐ－５のＭｎは２００００であり、Ｍｗは４１０００であり、Ｍｗ／Ｍｎは３．２であった。含フッ素重合体Ｐ－５の含フッ素部分の含有量は５６．４質量％であった。 [Comparative Example 2]
Except that the charged amount of HEMA was changed to 0.91 g and the charged amount of 3FM was changed to 1.07 g, the same procedure as in Example 1 was used to prepare a fluoropolymer P-5, which is a random copolymer of HEMA and 3FM. 1.46 g were obtained.
Mn of the fluoropolymer P-5 was 20,000, Mw was 41,000, and Mw / Mn was 3.2. The content of the fluorinated moiety in the fluorinated polymer P-5 was 56.4% by mass.
［比較例３］
　ＨＥＭＡを使用しなかった以外は、実施例１と同様の手法で、３ＦＭの単独重合体である重合体Ｐ－６の１．７３ｇを得た。
　重合体Ｐ－６のＭｎは２００００であり、Ｍｗは４１０００であり、Ｍｗ／Ｍｎは３．２であった。 [Comparative Example 3]
Except that HEMA was not used, in the same manner as in Example 1, 1.73 g of a polymer P-6 which was a homopolymer of 3FM was obtained.
Mn of the polymer P-6 was 20,000, Mw was 41,000, and Mw / Mn was 3.2.
Figure JPOXMLDOC01-appb-C000003
Figure JPOXMLDOC01-appb-C000003
　各例の重合体の組成、及び評価結果を表１に示す。 組成 Table 1 shows the composition of the polymer of each example and the evaluation results.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
　表１に示すように、含フッ素部分Ｆを特定の比率で有する実施例１～３の含フッ素重合体は、含フッ素部分を有しない比較例１、含フッ素部分の含有量が高い比較例２、及びＨＭＥＡ単位を有しない比較例３の重合体に比べて、タンパク質吸着量が少なく、生体親和性に優れていた。
　なお、２０１８年７月１３日に出願された日本特許出願２０１８－１３３６２９号の明細書、特許請求の範囲及び要約書の全内容をここに引用し、本発明の明細書の開示として、取り入れるものである。 As shown in Table 1, the fluorinated polymers of Examples 1 to 3 having the fluorinated portion F at a specific ratio were Comparative Example 1 having no fluorinated portion and Comparative Example 2 having a high content of the fluorinated portion. And the polymer of Comparative Example 3 having no HMEA unit had a smaller amount of adsorbed protein and was excellent in biocompatibility.
The entire contents of the specification, claims and abstract of Japanese Patent Application No. 2018-133629 filed on July 13, 2018 are incorporated herein by reference as the disclosure of the specification of the present invention. It is.

Claims (5)

  1. 　２－ヒドロキシエチルメタクリレートに基づく単位と、含フッ素部分とを有する含フッ素重合体であって、
    　前記２－ヒドロキシエチルメタクリレートに基づく単位の含有量が、前記含フッ素重合体の総質量に対して５０質量％以上であり、
    　前記含フッ素部分が、フッ素原子が結合している炭素原子の数が１～１６のポリフルオロアルキル基を有する含フッ素重合開始剤に基づく部分、含フッ素マクロ開始剤に基づく部分、含フッ素単量体に基づく単位、及び含フッ素マクロモノマーに基づく単位からなる群から選ばれる少なくとも１種であり、
    　前記含フッ素部分の含有量が、前記含フッ素重合体の総質量に対して０．１～１６質量％である、含フッ素重合体。     A fluorine-containing polymer having a unit based on 2-hydroxyethyl methacrylate and a fluorine-containing moiety,
    The content of the unit based on the 2-hydroxyethyl methacrylate is 50% by mass or more based on the total mass of the fluoropolymer,
    The fluorinated moiety is a moiety based on a fluorinated polymerization initiator having a polyfluoroalkyl group having 1 to 16 carbon atoms to which a fluorine atom is bonded, a moiety based on a fluorinated macroinitiator, a fluorinated monomer. At least one selected from the group consisting of units based on a body, and units based on a fluorinated macromonomer,
    A fluorinated polymer, wherein the content of the fluorinated moiety is 0.1 to 16% by mass relative to the total mass of the fluorinated polymer.
  2. 　示差走査熱量法で測定される中間水量が０．５質量％以上である、請求項１に記載の含フッ素重合体。 The fluoropolymer according to claim 1, wherein the amount of intermediate water measured by a differential scanning calorimetry is 0.5% by mass or more.
  3. 　請求項１又は２に記載の含フッ素重合体を含む膜。 膜 A film comprising the fluoropolymer according to claim 1 or 2.
  4. 　水中における膜表面の気泡接触角が１３５°以上である、請求項３に記載の膜。 The membrane according to claim 3, wherein the bubble contact angle of the membrane surface in water is 135 ° or more.
  5. 　基材と、前記基材上に形成された請求項３又は４に記載の膜とを有する医療用具。 (5) A medical device having a base material and the film according to claim 3 formed on the base material.
PCT/JP2019/026123 2018-07-13 2019-07-01 Fluorine-containing polymer, film, and medical instrument WO2020013010A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2018133629A JP2021165321A (en) 2018-07-13 2018-07-13 Fluorine-containing polymer, film and medical instrument
JP2018-133629 2018-07-13

Publications (1)

Publication Number Publication Date
WO2020013010A1 true WO2020013010A1 (en) 2020-01-16

Family

ID=69141425

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2019/026123 WO2020013010A1 (en) 2018-07-13 2019-07-01 Fluorine-containing polymer, film, and medical instrument

Country Status (2)

Country Link
JP (1) JP2021165321A (en)
WO (1) WO2020013010A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5155391A (en) * 1974-09-17 1976-05-15 Nat Res Dev HIDOROGER UKEISEI HORIMAA
JPH0348811A (en) * 1989-07-18 1991-03-01 Tome Sangyo Kk Solution for contact lens
JPH04114016A (en) * 1990-09-05 1992-04-15 Asahi Chem Ind Co Ltd Material for water-containing soft contact lens
JP2018537729A (en) * 2015-10-12 2018-12-20 メディオス カンパニー リミテッドＭｅｄｉｏｓ Ｃｏ．， Ｌｔｄ． Photochromic soft contact lens composition and method for producing the same

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5155391A (en) * 1974-09-17 1976-05-15 Nat Res Dev HIDOROGER UKEISEI HORIMAA
JPH0348811A (en) * 1989-07-18 1991-03-01 Tome Sangyo Kk Solution for contact lens
JPH04114016A (en) * 1990-09-05 1992-04-15 Asahi Chem Ind Co Ltd Material for water-containing soft contact lens
JP2018537729A (en) * 2015-10-12 2018-12-20 メディオス カンパニー リミテッドＭｅｄｉｏｓ Ｃｏ．， Ｌｔｄ． Photochromic soft contact lens composition and method for producing the same

Also Published As

Publication number Publication date
JP2021165321A (en) 2021-10-14

Similar Documents

Publication Publication Date Title
CN104039949B (en) Cell adhesion inhibitors
TWI725223B (en) Medical materials, medical separation membranes, and blood purifiers
WO2016140259A2 (en) Polymer and crosslinked body thereof
TWI706795B (en) Copolymer, antithrombotic coating agent and medical appliance using it
Koguchi et al. Understanding the effect of hydration on the bio-inert properties of 2-hydroxyethyl methacrylate copolymers with small amounts of amino-or/and fluorine-containing monomers
WO2020013010A1 (en) Fluorine-containing polymer, film, and medical instrument
JP2023153774A (en) Copolymer for inhibiting adhesion of protein, method for producing copolymer, resin modifier, molding material, copolymer-containing composition, coating film and article
WO2018003821A1 (en) Copolymer and application therefor
Lewis et al. Synthesis and characterisation of cationically modified phospholipid polymers
JP3580022B2 (en) Block copolymers and medical materials
Tanaka Design of novel biointerfaces (I). Blood compatibility of poly (2‐methoxyethyl acrylate)
Kurokawa et al. Antithrombogenic poly (2-methoxyethyl acrylate) elastomer via triblock copolymerization with poly (methyl methacrylate)
WO2020013009A1 (en) Fluorine-containing polymer, film, and medical instrument
JP2003192728A (en) Vinyl polymerizable monomer having tertiary hydroxyl group
JP2017186291A (en) N-phenylmaleimide derivative and manufacturing method therefor, precursor of n-phenylmaleimide derivative, polymer, protein adhesion prevention agent and medical device
JP2018009137A (en) Polymer, coating composition, and article
Koguchi et al. Altering the bio-inert properties of surfaces by fluorinated copolymers of mPEGMA
JP6833673B2 (en) Antithrombotic block copolymer
WO2023190383A1 (en) Polymer composition
Shaik et al. Interpenetrating photopolymers for intraocular lens application
JP7459616B2 (en) Copolymers, medical coatings and medical devices
WO2020122193A1 (en) Medical device, method for producing medical device, and coating liquid
JP2022167430A (en) Medical coating agent and medical device
JP6781595B2 (en) Method for surface hydrophilization treatment of polymer, method for producing surface hydrophilized article and surface hydrophilized article
JP6828876B2 (en) Radial polymers and their design methods

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: 19833449

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19833449

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP