WO2020013010A1 - Polymère contenant du fluor, membrane et instrument médical - Google Patents

Polymère contenant du fluor, membrane et instrument médical Download PDF

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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
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fluorine
fluorinated
mass
polymer
moiety
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PCT/JP2019/026123
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English (en)
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
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Ａｇｃ株式会社
国立大学法人九州大学
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Publication of WO2020013010A1 publication Critical patent/WO2020013010A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • 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.

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Abstract

L'invention concerne un polymère contenant du fluor, excellent en termes de biocompatibilité et de résistance à l'eau, et peu susceptible d'absorber un constituant biologique de protéines ou similaires; une membrane mettant en oeuvre ce polymère contenant du fluor; ainsi qu'un instrument médical.　Ce polymère contenant du fluor possède une unité à base de méthacrylate de 2-hydroxyéthyle et un groupe caractéristique contenant du fluor et est tel que: la teneur en unité à base de méthacrylate de 2-hydroxyéthyle est d'au moins 50% en poids du poids total du polymère contenant du fluor; le groupe caractéristique contenant du fluor est au moins un élément choisi dans le groupe comprenant un groupe caractéristique à base d'un initiateur de polymérisation contenant du fluor possédant un groupe C1-16 polyfluoroalkyle lié à un atome de fluor, un groupe caractéristique à base d'un macroiniateur contenant du fluor, une unité à base monomère contenant du fluor, et une unité à base de macromonomère contenant du fluor; la teneur en groupe caractéristique contenant du fluor est comprise entre 0,1 et 16% en poids du poids total du polymère contenant du fluor.
PCT/JP2019/026123 2018-07-13 2019-07-01 Polymère contenant du fluor, membrane et instrument médical WO2020013010A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5155391A (ja) * 1974-09-17 1976-05-15 Nat Res Dev Hidorogerukeiseihorimaa
JPH0348811A (ja) * 1989-07-18 1991-03-01 Tome Sangyo Kk コンタクトレンズ用溶液及びそれを用いたコンタクトレンズの親水化方法
JPH04114016A (ja) * 1990-09-05 1992-04-15 Asahi Chem Ind Co Ltd 含水ソフトコンタクトレンズ材料
JP2018537729A (ja) * 2015-10-12 2018-12-20 メディオス カンパニー リミテッドＭｅｄｉｏｓ Ｃｏ．， Ｌｔｄ． 光変色性ソフトコンタクトレンズ組成物及びその製造方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5155391A (ja) * 1974-09-17 1976-05-15 Nat Res Dev Hidorogerukeiseihorimaa
JPH0348811A (ja) * 1989-07-18 1991-03-01 Tome Sangyo Kk コンタクトレンズ用溶液及びそれを用いたコンタクトレンズの親水化方法
JPH04114016A (ja) * 1990-09-05 1992-04-15 Asahi Chem Ind Co Ltd 含水ソフトコンタクトレンズ材料
JP2018537729A (ja) * 2015-10-12 2018-12-20 メディオス カンパニー リミテッドＭｅｄｉｏｓ Ｃｏ．， Ｌｔｄ． 光変色性ソフトコンタクトレンズ組成物及びその製造方法

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