JPWO2015087966A1 - Antithrombotic material, antithrombogenic article, antibacterial material, antibacterial article, and method for inhibiting proliferation of Escherichia coli on article surface - Google Patents

Abstract

The present invention inhibits the growth of antithrombotic materials and antithrombotic materials and antithrombotic materials with improved antithrombogenicity and heat resistance, antimicrobial materials and antimicrobial products with improved antimicrobial properties and heat resistance, and growth of Escherichia coli on the surface of the articles. It aims to provide a new method. The present invention comprises a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit, and the content of the fluorine-containing olefin unit in the fluorine-containing copolymer is 30 to 60 mol%. Thrombotic material.

Description

The present invention relates to an antithrombotic material, an antithrombotic article, an antibacterial material, an antibacterial article, and a method for inhibiting the growth of E. coli on the article surface.

When an artificial material is brought into contact with a biological component, proteins, platelets, and the like adhere to the surface, which may cause problems such as deterioration in material performance and adverse effects on biological reactions. Therefore, surface biocompatibility is strongly required for an artificial material used for contact with a biological component.

Conventionally, ethylene / vinyl alcohol copolymers have been used as biocompatible materials. However, there was room for improving antithrombogenicity.

Materials other than the ethylene / vinyl alcohol copolymer have been studied, and Patent Document 1 discloses a polymer capable of maintaining a mixed phase in a glassy state with 2-methoxyethyl polyacrylate at room temperature, and 2-methoxyethyl polyacrylate. The biocompatible material is characterized in that the mixture has an inclined structure in which the 2-methoxyethyl polyacrylate is segregated on the surface side.

In Patent Document 2, at least a part of the surface is composed of a hydrophobic fluorine resin, a fluorine-containing monomer, a hydrophilic monomer, or a hydrophilic fluorine resin made of a copolymer of a hydrophilic monomer or a monomer that can be made hydrophilic after polymerization. A biocompatible substrate characterized by is described.

Patent Document 3 includes a medical article that includes a coating disposed on at least a portion of an implantable medical device, the coating including (a) a fluorinated polymer, and (b) a biobeneficial polymer. Medical articles are described.

In Patent Document 4, as a film used for water treatment or medical use, a copolymer of tetrafluoroethylene (TFE) and vinyl acetate (VAc) or at least a part of an acetate group contained in the copolymer is described. There is described a fluorine-containing copolymer film comprising a saponified copolymer and having a tetrafluoroethylene content of 1 to 70 mol% contained in the copolymer. Example 3 of Patent Document 4 describes a fluorine-containing copolymer having a saponification degree of 82% obtained by hydrolyzing a TFE / VAc copolymer having a TFE: VAc molar ratio of 23:77. .

Patent Document 5 describes a copolymer obtained by deprotecting a copolymer of tetrafluoroethylene and t-butyl vinyl ether or vinyl acetate as a hydrophilizing material used for an aqueous liquid separation membrane. .

JP2013-121430A Japanese Patent No. 2957023 Special table 2007-515208 JP-A-5-261256 International Publication No. 2012/165503

The present invention has been made in view of the above circumstances, and antithrombotic materials and antithrombotic articles with improved antithrombogenicity and heat resistance, antimicrobial materials and antimicrobial articles with improved antimicrobial and heat resistance, Another object of the present invention is to provide a novel method for inhibiting the growth of E. coli on the surface of an article.

In the fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit, the inventors of the present invention have a heat resistance, antithrombogenicity (antiplatelet adhesion), I found that antibacterial properties improved. Moreover, it has been found that when a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit is applied to the surface of an article, the growth of E. coli can be inhibited, and the present invention has been achieved.

That is, the present invention comprises a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit, and the content of the fluorine-containing olefin unit in the fluorine-containing copolymer is 30 to 60 mol%. Antithrombotic material.

In the antithrombogenic material of the present invention, it is preferable that the alternating rate of the fluorine-containing olefin unit and the vinyl alcohol unit in the fluorine-containing copolymer is 10 to 100%.

In the antithrombogenic material of the present invention, the fluorine-containing olefin is preferably at least one selected from the group consisting of tetrafluoroethylene, chlorotrifluoroethylene, and hexafluoropropylene.

In the antithrombogenic material of the present invention, the fluorine-containing copolymer preferably has a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit.

In the antithrombogenic material of the present invention, the fluorine-containing copolymer is preferably a copolymer obtained by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit.

The antithrombogenic material of the present invention is preferably treated on the surface with an aqueous solution containing an organic solvent.

The antithrombogenic material of the present invention is preferably a coating film.

The present invention is also an antithrombotic article made of the above antithrombotic material, which is a vial, an artificial blood vessel, a stent, a catheter, an artificial heart, an artificial lung, an artificial heart valve, or a blood storage bag. .

The present invention consists of a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit, and the content of the fluorine-containing olefin unit in the fluorine-containing copolymer is 10 to 60 mol%. It is also a sex material.

In the antibacterial material of the present invention, it is preferable that the alternating rate of the fluorine-containing olefin unit and the vinyl alcohol unit in the fluorine-containing copolymer is 10 to 100%.

In the antibacterial material of the present invention, the fluorine-containing olefin is preferably at least one selected from the group consisting of tetrafluoroethylene, chlorotrifluoroethylene, and hexafluoropropylene.

In the antibacterial material of the present invention, the fluorine-containing copolymer preferably has a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit.

In the antibacterial material of the present invention, the fluorine-containing copolymer is preferably a copolymer obtained by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit.

The antibacterial material of the present invention is preferably treated on the surface with an aqueous solution containing an organic solvent.

The antibacterial material of the present invention is preferably a coating film.

The present invention is also an antibacterial article made of the above antibacterial material, which is a contact lens, toiletry product, kitchen watering device, air conditioner, food factory facility, sewage treatment plant facility, or drain pipe.

The present invention is a method for inhibiting the growth of Escherichia coli on the surface of an article, characterized in that a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit is applied to the surface of the article.

According to the present invention, an antithrombotic material and an antithrombotic article having improved antithrombogenicity, an antimicrobial material and antimicrobial article having improved antimicrobial properties, and a novel method for inhibiting the growth of Escherichia coli on the surface of the article. Can be provided. Further, according to the present invention, the antithrombotic material and the antithrombotic article having high heat resistance and high durability against the heating and heat sterilization treatment during molding, the temperature rise during use, and the antibacterial property Materials and antimicrobial articles can be provided.

1 is a scanning electron microscope (SEM) photograph of the coating film surface in the evaluation of the adhesion of Escherichia coli in Example 6. FIG. FIG. 2 is a scanning electron microscope (SEM) photograph of the PET film surface in the evaluation of the adhesion of Escherichia coli of Comparative Example 6.

Hereinafter, the present invention will be specifically described.

The antithrombogenic material of the present invention comprises a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit (—CH ₂ —CH (OH) —), and the fluorine-containing olefin unit in the fluorine-containing copolymer The content is 30 to 60 mol%. The fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit is —CH (OH) —CXY— (wherein X and Y are the same or different and each represents H, F or a fluoroalkyl group, provided that , At least one of X and Y is F or a fluoroalkyl group). For this reason, the antithrombotic material of the present invention is one in which the adhesion of platelets is strongly suppressed. Conventionally used ethylene / vinyl alcohol copolymers do not have the above-mentioned fluoroalcohol structure and cannot sufficiently suppress platelet adhesion. Moreover, even if it is a fluorine-containing copolymer which has a fluorine-containing olefin unit and a vinyl alcohol unit, that whose content rate of a fluorine-containing olefin unit is lower than the said range is inferior to heat resistance.

Moreover, it is thought that the antithrombotic action of the said fluorine-containing copolymer originates not only in the said fluoroalcohol structure but also in a hydrophilic / hydrophobic phase separation structure or a sea-island structure. The fluorine-containing copolymer has a structure derived from a hydrophobic fluorine-containing olefin (for example, —CF ₂ CF ₂ —) and a hydrophilic hydroxyl structure, and the hydrophobic structure and the hydrophilic structure are respectively It is presumed that they gathered together to form a hydrophilic / hydrophobic phase separation structure or sea-island structure.

The fluorine-containing copolymer used for the antithrombogenic material of the present invention preferably contains 30 to 60 mol% of fluorine-containing olefin units and 40 to 70 mol% of vinyl alcohol units. When the content of each monomer unit is in such a range, the material made of the above-mentioned fluorine-containing copolymer becomes more excellent in antithrombogenicity and heat resistance. As a content rate of each monomer unit, it is more preferable that a fluorine-containing olefin unit is 35-60 mol%, a vinyl alcohol unit is 65-40 mol%, and a fluorine-containing olefin unit is 45-55 mol%. More preferably, the vinyl alcohol unit is 55 to 45 mol%.

The said fluorine-containing olefin unit represents the polymerization unit based on a fluorine-containing olefin. The fluorine-containing olefin is a monomer having a fluorine atom.

Examples of the fluorine-containing olefin include tetrafluoroethylene [TFE], vinylidene fluoride [VdF], chlorotrifluoroethylene [CTFE], vinyl fluoride, hexafluoropropylene [HFP], hexafluoroisobutene, CH ₂ = CZ. ¹ (CF ₂ ) _n1 Z ² (wherein Z ¹ is H, F or Cl, Z ² is H, F or Cl, and n1 is an integer of 1 to 10), CF ₂ = CF-ORf ¹ (wherein Rf ¹ represents a perfluoroalkyl group having 1 to 8 carbon atoms) and CF ₂ = CF-OCH ₂ -rf ² (wherein, Rf ² is a perfluoroalkyl group having 1 to 5 carbon atoms) selected from the group consisting of alkyl perfluorovinyl ether derivative represented by the It is preferably be at least one kind of fluorine-containing olefin.

Examples of the monomer represented by CH ₂ = CZ ¹ (CF ₂ ) _n1 Z ² include CH ₂ = CFCF ₃ , CH ₂ = CHCF ₃ , CH ₂ = CFCHF ₂ and CH ₂ = CClCF ₃ .

Examples of the PAVE include perfluoro (methyl vinyl ether) [PMVE], perfluoro (ethyl vinyl ether) [PEVE], perfluoro (propyl vinyl ether) [PPVE], perfluoro (butyl vinyl ether), and the like.

As said fluorine-containing olefin, at least 1 sort (s) selected from the group which consists of TFE, CTFE, and HFP is more preferable, and TFE is still more preferable.

The fluorine-containing copolymer preferably has an alternating rate of fluorine-containing olefin units and vinyl alcohol units of 10 to 100%. When the alternating rate is in such a range, the content of the fluoroalcohol structure in the fluorine-containing copolymer is further increased, and thus the adhesion of platelets to the antithrombotic material of the present invention is further strongly suppressed. More preferably, it is 25-100%, More preferably, it is 50-100%, Most preferably, it is 50-94%.

The alternating rate of the fluorinated olefin unit and the vinyl alcohol unit was determined by performing ¹ H-NMR measurement of the fluorinated copolymer using a solvent in which the fluorinated copolymer such as heavy acetone is dissolved, and calculating from the following formula: It can be calculated as the alternating rate of chaining.
Alternating rate (%) = C / (A + B + C) × 100
A: The number of V combined with two Vs such as -VVVV- B: The number of V combined with V and T as -VVT- C: -TV- Number of V bonded to two T like T- (T: fluorine-containing olefin unit, V: vinyl alcohol unit)
The number of V units of A, B, and C is calculated from the intensity ratio of H of the main chain bonded to the tertiary carbon of the vinyl alcohol unit (—CH ₂ —CH (OH) —) of ¹ H-NMR measurement. The estimation of the strength ratio of H in the main chain by ¹ H-NMR measurement was performed on the fluorine-containing copolymer before saponification.

The above fluorine-containing copolymer is -CH (OH) -CXY- (wherein X and Y are the same or different and each represents H, F or a fluoroalkyl group, provided that at least one of X and Y Is F or a fluoroalkyl group). The fluorine-containing copolymer, among others, -CH (OH) -CF ₂ - is preferably a fluorine alcohol structure represented by.

The fluorine-containing copolymer preferably contains 10 to 50 mol% of vinyl alcohol units constituting the fluorine alcohol structure based on all monomer units. As for the content rate of the vinyl alcohol unit which comprises a fluorine alcohol structure, it is more preferable that it is 15-50 mol%, and it is still more preferable that it is 30-50 mol%.

The fluorine-containing copolymer is further represented by —CH ₂ —CH (O (C═O) R) — (wherein R represents a hydrogen atom or a hydrocarbon group having 1 to 17 carbon atoms). It may have a vinyl ester monomer unit. Thus, it is also one of the preferred embodiments of the present invention that the fluorinated copolymer in the present invention has a fluorinated olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit. Furthermore, it is a fluorine-containing olefin / vinyl alcohol / vinyl ester monomer copolymer consisting essentially of a fluorine-containing olefin unit, a vinyl alcohol unit and a vinyl ester monomer unit. One.

The vinyl ester monomer unit is a monomer represented by —CH ₂ —CH (O (C═O) R) — (wherein R represents a hydrogen atom or a hydrocarbon group having 1 to 17 carbon atoms). Although it is a unit, as R in the said formula, a C1-C11 alkyl group is preferable and a C1-C5 alkyl group is more preferable. Particularly preferred is an alkyl group having 1 to 3 carbon atoms.

Examples of the vinyl ester monomer unit include monomer units derived from the following vinyl esters.
Vinyl formate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl isobutyrate, vinyl valelate, vinyl isovalerate, vinyl caproate, vinyl heptylate, vinyl caprylate, vinyl pivalate, vinyl pelargonate, vinyl caprate, Vinyl laurate, vinyl myristate, vinyl pentadecylate, vinyl palmitate, vinyl margarate, vinyl stearate, vinyl octylate, Veova-9 (manufactured by Showa Shell Sekiyu KK), Veova-10 (Showa Shell Sekiyu KK) )), Vinyl benzoate, vinyl versatate.
Among these, monomer units derived from vinyl acetate, vinyl propionate, and vinyl versatate are preferable. More preferred are vinyl acetate monomer units and vinyl propionate monomer units, and even more preferred are vinyl acetate monomer units.

When the fluorine-containing copolymer has a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit, the content of each monomer unit is 30 to 60 mol% of the fluorine-containing olefin unit, and vinyl alcohol Preferably, the units are greater than 0 mol% and less than 70 mol%, and the vinyl ester monomer units are greater than 0 mol% and less than 70 mol%. When the content of each monomer unit is in such a range, the material made of the above-mentioned fluorine-containing copolymer becomes more excellent in antithrombogenicity and heat resistance. The content of each monomer unit is such that the fluorinated olefin unit is 30 to 60 mol%, the vinyl alcohol unit is 70 to 40 mol%, and the vinyl ester monomer unit is 0.1 to 20 mol%. More preferably, the fluorine-containing olefin unit is 35 to 60 mol%, the vinyl alcohol unit is 75 to 40 mol%, and the vinyl ester monomer unit is further preferably 0.5 to 10 mol%.

When the fluorine-containing copolymer has a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit, the alternating rate of the fluorine-containing olefin unit, the vinyl alcohol unit, and the vinyl ester monomer unit is 10 to 100%. It is preferable. When the alternating rate is within such a range, the content of the fluoroalcohol structure in the fluorinated copolymer is further increased, so that the adhesion of platelets to the material comprising the fluorinated copolymer is more strongly suppressed. . More preferably, it is 25-100%, More preferably, it is 50-100%, Most preferably, it is 50-94%.

The alternating rate of the fluorinated olefin unit, the vinyl alcohol unit, and the vinyl ester monomer unit is determined by performing ¹ H-NMR measurement of the fluorinated copolymer using a solvent in which the fluorinated copolymer such as heavy acetone is dissolved, It can be calculated as an alternating rate of three chains from the following formula.
Alternating rate (%) = C / (A + B + C) × 100
A: The number of V combined with two Vs such as -VVVV- B: The number of V combined with V and T as -VVT- C: -TV- Number of Vs bonded to two Ts such as T- (T: fluorinated olefin unit, V: vinyl alcohol unit or vinyl ester monomer unit)
The number of V units of A, B, and C is the vinyl alcohol unit (—CH ₂ —CH (OH) —) and vinyl ester monomer unit (—CH ₂ —CH (O (C═O)) of ¹ H-NMR measurement. Calculated from the intensity ratio of H of the main chain bonded to the tertiary carbon of R)-). The estimation of the strength ratio of H in the main chain by ¹ H-NMR measurement was performed on the fluorine-containing copolymer before saponification.

The said fluorine-containing copolymer may have other monomer units other than a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit in the range which does not impair the effect of this invention.

As said other monomer, as a monomer which does not contain a fluorine atom (however, except vinyl alcohol and a vinyl ester monomer), for example, ethylene, propylene, 1-butene, 2-butene, vinyl chloride, Preference is given to at least one fluorine-free ethylenic monomer selected from the group consisting of vinylidene chloride, vinyl ether monomers and unsaturated carboxylic acids.

The total content of the other monomer units is preferably 0 to 50 mol%, more preferably 0 to 40 mol%, based on all monomer units of the fluorine-containing copolymer, More preferably, it is 30 mol%.

In the present specification, the content of each monomer unit constituting the fluorine-containing copolymer can be calculated by appropriately combining NMR, FT-IR, and elemental analysis depending on the type of monomer.

The weight average molecular weight of the fluorine-containing copolymer is not particularly limited, but is preferably 10,000 or more. More preferably, it is 12,000-2,000,000, More preferably, it is 12,000-1,000,000.
The weight average molecular weight can be determined by gel permeation chromatography (GPC).

As described later, the fluorine-containing copolymer can be produced by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit. That is, the fluorine-containing copolymer in the present invention is a copolymer obtained by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit. One.

Below, the manufacturing method of the fluorine-containing copolymer in this invention is demonstrated.
Usually, the fluorine-containing copolymer in the present invention is produced by copolymerizing a fluorine-containing olefin such as tetrafluoroethylene and a vinyl ester monomer such as vinyl acetate, and then saponifying the obtained copolymer. can do. As a method for polymerizing the fluorine-containing copolymer, it is preferable to carry out the polymerization under a condition in which the composition ratio of the fluorine-containing olefin and the vinyl ester monomer is kept substantially constant. That is, the above-mentioned fluorine-containing copolymer is polymerized under a condition in which the composition ratio of the fluorine-containing olefin and the vinyl ester monomer is kept almost constant to obtain a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit. It is preferably obtained by a production method comprising a step and a step of saponifying the obtained copolymer to obtain a copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit.

Examples of the vinyl ester monomers include vinyl formate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl isobutyrate, vinyl valerate, vinyl isovalerate, vinyl caproate, vinyl heptylate, vinyl caprylate, vinyl pivalate, pelargon. Vinyl acetate, vinyl caprate, vinyl laurate, vinyl myristate, vinyl pentadecylate, vinyl palmitate, vinyl margarate, vinyl stearate, vinyl octylate, Veova-9 (manufactured by Showa Shell Sekiyu KK), Veova 10 (manufactured by Showa Shell Sekiyu KK), vinyl benzoate, vinyl versatate, and the like. Of these, vinyl acetate, vinyl propionate, and vinyl versatate are preferably used because they are easily available and inexpensive.
As said vinyl ester monomer, 1 type of these may be used and 2 or more types may be mixed and used.

Examples of the method of copolymerizing the fluorinated olefin and the vinyl ester monomer include solution polymerization, bulk polymerization, emulsion polymerization, suspension polymerization and the like, and emulsion polymerization is easy because it is industrially easy to implement. However, it is preferable to produce by solution polymerization or suspension polymerization, but not limited thereto.

In emulsion polymerization, solution polymerization, or suspension polymerization, a polymerization initiator, a solvent, a chain transfer agent, a surfactant, a dispersant, and the like can be used, and those usually used can be used.

The solvent used in the solution polymerization is preferably a solvent capable of dissolving the fluorine-containing olefin, the vinyl ester monomer, and the fluorine-containing copolymer to be synthesized. For example, n-butyl acetate, t-butyl acetate, ethyl acetate Esters such as methyl acetate and propyl acetate; Ketones such as acetone, methyl ethyl ketone and cyclohexanone; Aliphatic hydrocarbons such as hexane, cyclohexane and octane; Aromatic hydrocarbons such as benzene, toluene and xylene; Methanol and ethanol , Tert-butanol, alcohols such as 2-propanol; cyclic ethers such as tetrahydrofuran and dioxane; fluorine-containing solvents such as HCFC-225; dimethyl sulfoxide, dimethylformamide, or a mixture thereof.
Examples of the solvent used in the emulsion polymerization include water, a mixed solvent of water and alcohol, and the like.

Examples of the polymerization initiator include peroxycarbonates such as diisopropyl peroxydicarbonate (IPP) and di-n-propyl peroxydicarbonate (NPP), and t-butyl peroxypivalate (for example, NOF Corporation). Oil-soluble radical polymerization initiators typified by peroxyesters such as perbutyl PV), for example, persulfuric acid, perboric acid, perchloric acid, perphosphoric acid, ammonium percarbonate, potassium salt, sodium Water-soluble radical polymerization initiators such as salts can be used. Particularly in emulsion polymerization, ammonium persulfate and potassium persulfate are preferred.

As the surfactant, a commonly used surfactant can be used. For example, a nonionic surfactant, an anionic surfactant, a cationic surfactant and the like can be used. Moreover, you may use a fluorine-containing surfactant.

Examples of the dispersant used in suspension polymerization include partially saponified polyvinyl acetate, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and other water-soluble cellulose ethers used in ordinary suspension polymerization, and acrylic acid polymers. And water-soluble polymers such as gelatin. The suspension polymerization is carried out under the condition that the water / monomer ratio is usually 1.5 / 1 to 3/1 by weight, and the dispersant is 0.01 to 0 with respect to 100 parts by weight of the monomer. 1 part by weight is used. If necessary, a pH buffer such as polyphosphate can be used.

Examples of the chain transfer agent include hydrocarbons such as ethane, isopentane, n-hexane, and cyclohexane; aromatics such as toluene and xylene; ketones such as acetone; and acetates such as ethyl acetate and butyl acetate; Examples include alcohols such as methanol and ethanol; mercaptans such as methyl mercaptan; halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride, and methyl chloride.
The amount of the chain transfer agent added may vary depending on the size of the chain transfer constant of the compound used, but is usually used in the range of 0.001 to 10% by mass relative to the polymerization solvent.

The polymerization temperature may be in a range where the composition ratio during the reaction of the fluorinated olefin and the vinyl ester monomer is substantially constant, and may be 0 to 100 ° C.

The polymerization pressure may be in a range in which the composition ratio during the reaction of the fluorinated olefin and the vinyl ester monomer is substantially constant, and may be 0 to 10 MPaG.

Saponification of an acetate group derived from vinyl acetate is well known in the art, and can be performed by a conventionally known method such as alcoholysis or hydrolysis. By this saponification, the acetate group (—OCOCH ₃ ) is converted into a hydroxyl group (—OH). Similarly, other vinyl ester monomers can be saponified by a conventionally known method to obtain a hydroxyl group.

The degree of saponification in the case of obtaining a fluorine-containing copolymer in the present invention by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit is the content of each monomer unit of the fluorine-containing copolymer in the present invention. It is sufficient that the rate is within the above-mentioned range, specifically, 50% or more is preferable, 60% or more is more preferable, and 70% or more is still more preferable.

The saponification degree is calculated from the following equation by IR measurement or ¹ H-NMR measurement of the fluorine-containing copolymer.
Saponification degree (%) = D / (D + E) × 100
D: number of vinyl alcohol units in the fluorinated copolymer E: number of vinyl ester monomer units in the fluorinated copolymer

The fluorine-containing copolymer in the present invention is a vinyl ether monomer (CH ₂ = CH-OR) (hereinafter simply referred to as a vinyl ether monomer) in which a fluorine-containing olefin and a protecting group (R) that can be converted to vinyl alcohol by deprotection reaction are bonded. And a fluorine-containing olefin / vinyl alcohol copolymer by deprotecting the fluorine-containing olefin / vinyl ether copolymer. It can obtain also by the manufacturing method which consists of a process of obtaining.

A method for copolymerizing the fluorinated olefin and the vinyl ether monomer and a method for deprotecting the fluorinated olefin / vinyl ether copolymer are well known in the art. It can be carried out. By deprotecting the fluorinated olefin / vinyl ether copolymer, the protecting group alkoxy group is converted to a hydroxyl group, and a fluorinated olefin / vinyl alcohol copolymer is obtained.

The fluorine-containing olefin / vinyl ether copolymer obtained by copolymerizing the fluorine-containing olefin and the vinyl ether monomer is a molar ratio of the fluorine-containing olefin and the vinyl ether monomer (fluorine-containing olefin) / (vinyl ether unit The (mer) is preferably (30-60) / (70-40), and more preferably (45-55) / (55-45). When the molar ratio is within the above range and the degree of deprotection is within the range described later, it is possible to produce a fluorinated copolymer in which the molar ratio of each polymerized unit is within the above range.

The vinyl ether monomer preferably does not contain a fluorine atom. The vinyl ether monomer is not particularly limited as long as it is deprotected, but tertiary butyl vinyl ether is preferable from the viewpoint of availability.

When the said fluorine-containing copolymer has a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ether unit, it is preferable that the alternating rate of a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ether unit is 10 to 100%. When the alternating rate is within such a range, the content of the fluoroalcohol structure in the fluorinated copolymer is further increased, so that the adhesion of platelets to the material comprising the fluorinated copolymer is more strongly suppressed. . More preferably, it is 25-100%, More preferably, it is 50-100%, Most preferably, it is 50-94%.

The alternating rate of the fluorinated olefin unit, the vinyl alcohol unit and the vinyl ether unit was measured by ¹ H-NMR measurement of the fluorinated copolymer using a solvent in which the fluorinated copolymer such as heavy acetone was dissolved. It can be calculated as an alternating rate of three chains from the equation.
Alternating rate (%) = C / (A + B + C) × 100
A: The number of V combined with two Vs such as -VVVV- B: The number of V combined with V and T as -VVT- C: -TV- Number of Vs bonded to two Ts such as T- (T: fluorine-containing olefin unit, V: vinyl alcohol unit or vinyl ether unit)
The number of V units of A, B, and C is the tertiary carbon of vinyl alcohol unit (—CH ₂ —CH (OH) —) and vinyl ether unit (—CH ₂ —CH (OR)) measured by ¹ H-NMR. It calculates from the intensity ratio of H of the main chain to couple | bond. The estimation of the strength ratio of H in the main chain by ¹ H-NMR measurement was performed on the fluorine-containing copolymer before deprotection.

Examples of the method for copolymerizing the fluorine-containing olefin and the vinyl ether monomer include solution polymerization, bulk polymerization, emulsion polymerization, suspension polymerization, and the like, which are industrially easy to implement. Although it is preferable to manufacture by emulsion polymerization, solution polymerization, or suspension polymerization, it is not this limitation.

In the above emulsion polymerization, solution polymerization or suspension polymerization, a polymerization initiator, a solvent, a chain transfer agent, a surfactant, a dispersant and the like can be used, and those usually used can be used.

The solvent used in the solution polymerization is preferably a solvent capable of dissolving the fluorine-containing olefin, the vinyl ether monomer, and the fluorine-containing copolymer to be synthesized. For example, n-butyl acetate, t-butyl acetate, Esters such as ethyl acetate, methyl acetate and propyl acetate; Ketones such as acetone, methyl ethyl ketone and cyclohexanone; Aliphatic hydrocarbons such as hexane, cyclohexane and octane; Aromatic hydrocarbons such as benzene, toluene and xylene; Methanol Alcohols such as ethanol, tert-butanol and 2-propanol; cyclic ethers such as tetrahydrofuran and dioxane; fluorine-containing solvents such as HCFC-225; dimethyl sulfoxide, dimethylformamide, and mixtures thereof.
Examples of the solvent used in the emulsion polymerization include water, a mixed solvent of water and alcohol, and the like.

Examples of the polymerization initiator include peroxycarbonates such as diisopropyl peroxydicarbonate (IPP) and di-n-propyl peroxydicarbonate (NPP), and t-butyl peroxypivalate (for example, NOF Corporation). Oil-soluble radical polymerization initiators typified by peroxyesters such as perbutyl PV), for example, persulfuric acid, perboric acid, perchloric acid, perphosphoric acid, ammonium percarbonate, potassium salt, sodium Water-soluble radical polymerization initiators such as salts can be used. Particularly in emulsion polymerization, ammonium persulfate and potassium persulfate are preferred.

As the surfactant, a commonly used surfactant can be used. For example, a nonionic surfactant, an anionic surfactant, a cationic surfactant and the like can be used. Moreover, you may use a fluorine-containing surfactant.

Examples of the dispersant used in suspension polymerization include partially saponified polyvinyl acetate, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and other water-soluble cellulose ethers used in ordinary suspension polymerization, and acrylic acid polymers. And water-soluble polymers such as gelatin. The suspension polymerization is carried out under the condition that the water / monomer ratio is usually 1.5 / 1 to 3/1 by weight, and the dispersant is 0.01 to 0 with respect to 100 parts by weight of the monomer. 1 part by weight is used. If necessary, a pH buffer such as polyphosphate can be used.

Examples of the chain transfer agent include hydrocarbons such as ethane, isopentane, n-hexane, and cyclohexane; aromatics such as toluene and xylene; ketones such as acetone; and acetates such as ethyl acetate and butyl acetate; Examples include alcohols such as methanol and ethanol; mercaptans such as methyl mercaptan; halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride, and methyl chloride.
The amount of the chain transfer agent added may vary depending on the size of the chain transfer constant of the compound used, but is usually used in the range of 0.001 to 10% by mass relative to the polymerization solvent.

The polymerization temperature may be in a range in which the composition ratio during the reaction of the fluorinated olefin and the vinyl ether monomer is substantially constant, and may be 0 to 100 ° C.

The polymerization pressure may be in a range where the composition ratio during the reaction of the fluorinated olefin and the vinyl ether monomer is substantially constant, and may be 0 to 10 MPaG.

The deprotection of the vinyl ether monomer can be performed by a conventionally known method such as acid, heat or light. By this deprotection, the leaving group (for example, —C (CH ₃ ) ₃ ) can be replaced with hydrogen to obtain a hydroxyl group.

The degree of deprotection in the case of obtaining the fluorine-containing copolymer in the present invention by deprotecting the copolymer having the above-mentioned fluorine-containing olefin unit and vinyl ether monomer unit is determined according to each monomer of the fluorine-containing copolymer in the present invention. The unit content may be in the range as described above, specifically 50% or more is preferable, 60% or more is more preferable, and 70% or more is still more preferable.

The degree of deprotection is calculated from the following formula by IR measurement of the fluorine-containing copolymer or the above-mentioned ¹ H-NMR measurement.
Deprotection degree (%) = D / (D + E) × 100
D: Number of vinyl alcohol units in the fluorinated copolymer E: Number of vinyl ether monomer units in the fluorinated copolymer

The antithrombogenic material of the present invention may further contain other components other than the above-mentioned fluorinated copolymer as long as the effects of the present invention are not impaired.

Examples of the other components include hydrophilic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, and polyethylene glycol.

The blending amount of the other component is preferably 1 to 30% by mass and more preferably 1 to 10% by mass with respect to 100% by mass of the fluorine-containing copolymer.

The antithrombogenic material of the present invention is preferably treated on the surface with an aqueous solution containing an organic solvent. By this surface treatment, the hydroxyl structure further increases on the surface of the antithrombotic material, so that platelet adhesion is more strongly suppressed.

The organic solvent that can be used in the surface treatment is not particularly limited as long as it is an organic solvent that is soluble in water and dissolves the fluorine-containing copolymer, but methanol, ethanol, 2-propanol, acetone, tetrahydrofuran , Methyl ethyl ketone, dimethylacetamide, dimethylformamide and the like. Of these, methanol, ethanol, 2-propanol and tetrahydrofuran are preferred.

Examples of the treatment method using the aqueous solution containing the organic solvent include a method of wetting the surface of the antithrombogenic material with the aqueous solution.

The antithrombogenic material of the present invention is provided by being molded into various shapes depending on the application. The molding method is not particularly limited, and spin coating method, drop casting method, dip nip method, spray coating method, brush coating method, dipping method, ink jet printing method, electrostatic coating method, compression molding method, extrusion molding method, calendar molding method. Methods, transfer molding methods, injection molding methods, lotto molding methods, lotining molding methods, thermally induced phase separation methods, non-solvent induced phase separation methods, and the like can be employed.

The antithrombogenic material of the present invention is preferably a coating film because it can be applied to articles having various shapes. A coating film means the film | membrane obtained by apply | coating the coating composition containing the said fluorine-containing copolymer or the said fluorine-containing copolymer. Examples of the method for forming the coating film include spin coating, drop casting, dip nip, spray coating, brush coating, dipping, electrostatic coating, and inkjet printing. Of these, spin coating, drop casting, and dipping are preferred from the standpoint of simplicity.

The coating film is preferably obtained by applying a coating composition containing the fluorine-containing copolymer and an organic solvent. As the organic solvent, methanol, ethanol, 2-propanol, 2-butanol, 1-butanol, 1-hexanol, acetone, tetrahydrofuran, methyl ethyl ketone, dimethylacetamide, dimethylformamide and the like can be used. Of these, 2-butanol, 1-butanol, 1-hexanol, and tetrahydrofuran are preferable in that a transparent and uniform coating film can be easily obtained. From the viewpoint of solubility of the fluorinated copolymer, methanol, ethanol, 2-propanol, tetrahydrofuran, and dimethylformamide are preferable.

When the antithrombogenic material of the present invention is a coating film, the film thickness is preferably 0.1 to 50 μm, more preferably 0.5 to 30 μm, and 1.0 to 20 μm. Further preferred.

Since the antithrombotic material of the present invention has excellent antithrombogenicity, it can be applied to various articles that require antithrombogenicity. Preferred examples of the article include vials, artificial blood vessels, stents, catheters, artificial hearts, artificial lungs, artificial heart valves, blood storage bags, and the like. An antithrombotic article comprising the antithrombotic material of the present invention, which is a vial, an artificial blood vessel, a stent, a catheter, an artificial heart, an artificial lung, an artificial heart valve, or a blood storage bag, is also provided. It is one of the inventions.

Although the aspect which applies the antithrombogenic material of this invention to the said antithrombogenic article is not specifically limited, The antithrombotic material of this invention is fully demonstrated in the point which exhibits the antithrombotic effect of the antithrombotic material of this invention. Is preferably applied so as to constitute at least the surface of the antithrombogenic article.

The present invention consists of a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit, and the content of the fluorine-containing olefin unit in the fluorine-containing copolymer is 10 to 60 mol%. It is also a sex material.

The antibacterial material of the present invention comprises a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit, and the content of the fluorine-containing olefin unit in the fluorine-containing copolymer is 10 to 60 mol%, 30 It is preferably ˜60 mol%. The fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit is —CH (OH) —CXY— (wherein X and Y are the same or different and each represents H, F or a fluoroalkyl group, provided that , At least one of X and Y is F or a fluoroalkyl group). For this reason, the antibacterial material of this invention can exhibit the outstanding antibacterial property. Conventionally used ethylene / vinyl alcohol copolymers do not have the above-mentioned fluorine alcohol structure and are not sufficiently antibacterial. Further, even in the case of a fluorinated copolymer having a fluorinated olefin unit and a vinyl alcohol unit, those having a fluorinated olefin unit content lower than the above range have a low content of the fluoroalcohol structure, Antibacterial property is not enough.

Further, the antibacterial action of the fluorine-containing copolymer is considered to be derived not only from the fluorine alcohol structure but also from a hydrophilic / hydrophobic phase separation structure or a sea-island structure. The fluorine-containing copolymer has a structure derived from a hydrophobic fluorine-containing olefin (for example, —CF ₂ CF ₂ —) and a hydrophilic hydroxyl structure, and the hydrophobic structure and the hydrophilic structure are respectively It is presumed that they gathered together to form a hydrophilic / hydrophobic phase separation structure or sea-island structure.

The fluorine-containing copolymer used for the antibacterial material of the present invention preferably contains 10 to 60 mol% of fluorine-containing olefin units and 40 to 90 mol% of vinyl alcohol units. When the content of each monomer unit is in such a range, the material made of the above-mentioned fluorine-containing copolymer becomes more excellent in antibacterial properties and heat resistance. The content of each monomer unit is preferably 30 to 60 mol% of the fluorinated olefin unit, more preferably 70 to 40 mol% of the vinyl alcohol unit, and 35 to 55 mol% of the fluorinated olefin unit. More preferably, the vinyl alcohol unit is 65 to 45 mol%, the fluorinated olefin unit is 45 to 55 mol%, and the vinyl alcohol unit is 55 to 45 mol%.

Examples of the fluorine-containing olefin constituting the fluorine-containing olefin unit include the fluorine-containing olefins exemplified for the fluorine-containing copolymer used in the antithrombogenic material of the present invention. As said fluorine-containing olefin, at least 1 sort (s) selected from the group which consists of TFE, CTFE, and HFP is more preferable, and TFE is still more preferable.

The fluorine-containing copolymer preferably has an alternating rate of fluorine-containing olefin units and vinyl alcohol units of 10 to 100%. When the alternating rate is within such a range, the content of the fluoroalcohol structure in the fluorine-containing copolymer is further increased, so that the antibacterial material of the present invention is further excellent in antibacterial properties. More preferably, it is 25-100%, More preferably, it is 50-100%, Most preferably, it is 50-94%.
The calculation method of the alternating rate of a fluorine-containing olefin unit and a vinyl alcohol unit is as having mentioned above.

The above fluorine-containing copolymer is -CH (OH) -CXY- (wherein X and Y are the same or different and each represents H, F or a fluoroalkyl group, provided that at least one of X and Y Is F or a fluoroalkyl group). The fluorine-containing copolymer, among others, -CH (OH) -CF ₂ - is preferably a fluorine alcohol structure represented by.

The fluorine-containing copolymer preferably contains 30 to 50 mol% of vinyl alcohol units constituting the above-described fluorine alcohol structure based on all monomer units. The content of vinyl alcohol units constituting the fluoroalcohol structure is more preferably 35 to 50 mol%, still more preferably 40 to 50 mol%.

The fluorine-containing copolymer is further represented by —CH ₂ —CH (O (C═O) R) — (wherein R represents a hydrogen atom or a hydrocarbon group having 1 to 17 carbon atoms). It may have a vinyl ester monomer unit. Thus, it is also one of the preferred embodiments of the present invention that the fluorinated copolymer in the present invention has a fluorinated olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit. Furthermore, it is a fluorine-containing olefin / vinyl alcohol / vinyl ester monomer copolymer consisting essentially of a fluorine-containing olefin unit, a vinyl alcohol unit and a vinyl ester monomer unit. One.

Examples of the vinyl ester monomer unit include monomer units derived from the vinyl ester monomer exemplified for the fluorine-containing copolymer used in the antithrombogenic material of the present invention. Of these, monomer units derived from vinyl acetate, vinyl propionate, and vinyl versatate are preferred. More preferred are vinyl acetate monomer units and vinyl propionate monomer units, and even more preferred are vinyl acetate monomer units.

When the fluorine-containing copolymer has a fluorine-containing olefin unit, a vinyl alcohol unit and a vinyl ester monomer unit, the content of each monomer unit is 10 to 60 mol% of the fluorine-containing olefin unit, and vinyl alcohol Preferably, the units are greater than 0 mol% and less than 90 mol%, and the vinyl ester monomer units are greater than 0 mol% and less than 70 mol%. When the content of each monomer unit is in such a range, the material made of the above-mentioned fluorine-containing copolymer becomes more excellent in antibacterial properties and heat resistance. The content of each monomer unit is such that the fluorinated olefin unit is 10 to 60 mol%, the vinyl alcohol unit is 90 to 40 mol%, and the vinyl ester monomer unit is 0.1 to 20 mol%. More preferably, the fluorine-containing olefin unit is 30 to 60 mol%, the vinyl alcohol unit is 70 to 40 mol%, the vinyl ester monomer unit is further preferably 0.1 to 20 mol%, and the fluorine-containing olefin is more preferable. It is particularly preferable that the unit is 35 to 60 mol%, the vinyl alcohol unit is 75 to 40 mol%, and the vinyl ester monomer unit is 0.5 to 10 mol%.

When the fluorine-containing copolymer has a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit, the alternating rate of the fluorine-containing olefin unit, the vinyl alcohol unit, and the vinyl ester monomer unit is 10 to 100%. It is preferable. When the alternating rate is within such a range, the content of the fluoroalcohol structure in the fluorine-containing copolymer is further increased, and thus the material comprising the fluorine-containing copolymer is further excellent in antibacterial properties. More preferably, it is 25-100%, More preferably, it is 50-100%, Most preferably, it is 50-94%.
The calculation method of the alternating rate of a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ester monomer unit is as having mentioned above.

The fluorine-containing copolymer used for the antibacterial material of the present invention has a monomer unit other than the fluorine-containing olefin unit, vinyl alcohol unit and vinyl ester monomer unit within the range not impairing the effects of the present invention. It may be. As said other monomer, the other monomer illustrated about the fluorine-containing copolymer used for the antithrombogenic material of this invention can be mentioned.

The total content of the other monomer units is preferably 0 to 50 mol%, more preferably 0 to 40 mol%, based on all monomer units of the fluorine-containing copolymer, More preferably, it is 30 mol%.

The weight average molecular weight of the fluorine-containing copolymer is not particularly limited, but is preferably 10,000 or more. More preferably, it is 12,000-2,000,000, More preferably, it is 12,000-1,000,000.
The weight average molecular weight can be determined by gel permeation chromatography (GPC).

The fluorine-containing copolymer used for the antibacterial material of the present invention can be produced by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit. That is, the fluorine-containing copolymer in the present invention is a copolymer obtained by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit. One. A specific production method is the same as the production method described for the fluorine-containing copolymer used for the antithrombotic material of the present invention.

The degree of saponification in the case of obtaining a fluorine-containing copolymer in the present invention by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit is the content of each monomer unit of the fluorine-containing copolymer in the present invention. It is sufficient that the rate is within the above-mentioned range, specifically, 50% or more is preferable, 60% or more is more preferable, and 70% or more is still more preferable.
The method for calculating the saponification degree is as described above.

The fluorine-containing copolymer used for the antibacterial material of the present invention is a vinyl ether monomer (CH ₂ = CH-OR) in which a fluorine-containing olefin and a protecting group (R) that can be converted to vinyl alcohol by a deprotection reaction are bonded. (Hereinafter simply referred to as a vinyl ether monomer) to obtain a fluorine-containing olefin / vinyl ether copolymer, and by deprotecting the fluorine-containing olefin / vinyl ether copolymer, It can also be obtained by a production method comprising the step of obtaining a vinyl alcohol copolymer.

A specific method for copolymerizing the fluorine-containing olefin and the vinyl ether monomer and a specific method for deprotecting the fluorine-containing olefin / vinyl ether copolymer are used for the antithrombogenic material of the present invention. This is the same as the method described for the fluorine-containing copolymer.

The fluorine-containing olefin / vinyl ether copolymer obtained by copolymerizing the fluorine-containing olefin and the vinyl ether monomer is a molar ratio of the fluorine-containing olefin and the vinyl ether monomer (fluorine-containing olefin) / (vinyl ether unit The (mer) is preferably (30-60) / (70-40), and more preferably (45-55) / (55-45). When the molar ratio is within the above range and the degree of deprotection is within the range described later, it is possible to produce a fluorinated copolymer in which the molar ratio of each polymerized unit is within the above range.

The deprotection of the fluorinated olefin / vinyl ether copolymer is preferably performed so that the degree of deprotection is 1 to 100%, and more preferably 30 to 100%. The degree of deprotection is more preferably 50% or more, still more preferably 60% or more, and particularly preferably 70% or more. The method for calculating the degree of deprotection is as described above.

When the said fluorine-containing copolymer has a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ether unit, it is preferable that the alternating rate of a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ether unit is 10 to 100%. When the alternating rate is within such a range, the content of the fluoroalcohol structure in the fluorine-containing copolymer is further increased, so that the antibacterial material of the present invention is further excellent in antibacterial properties. More preferably, it is 25-100%, More preferably, it is 50-100%, Most preferably, it is 50-94%.
The calculation method of the alternating rate of a fluorine-containing olefin unit, a vinyl alcohol unit, and a vinyl ether unit is as having mentioned above.

The antibacterial material of the present invention may further contain other components other than the fluorine-containing copolymer as long as the effects of the present invention are not impaired.

Examples of the other components include hydrophilic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, and polyethylene glycol.

The blending amount of the other component is preferably 1 to 30% by mass and more preferably 1 to 10% by mass with respect to 100% by mass of the fluorine-containing copolymer.

The antibacterial material of the present invention is preferably treated on the surface with an aqueous solution containing an organic solvent. By this surface treatment, a hydroxyl group structure is further increased on the surface of the antibacterial material, so that more excellent antibacterial properties are exhibited.

The organic solvent that can be used in the surface treatment is not particularly limited as long as it is an organic solvent that is soluble in water and dissolves the fluorine-containing copolymer, but methanol, ethanol, 2-propanol, acetone, tetrahydrofuran , Methyl ethyl ketone, dimethylacetamide, dimethylformamide and the like. Of these, methanol, ethanol, 2-propanol and tetrahydrofuran are preferred.

Examples of the treatment method using an aqueous solution containing the organic solvent include a method of wetting the surface with the aqueous solution.

The antibacterial material of the present invention is provided by being molded into various shapes depending on the application. The molding method is not particularly limited, and spin coating method, drop casting method, dip nip method, spray coating method, brush coating method, dipping method, ink jet printing method, electrostatic coating method, compression molding method, extrusion molding method, calendar molding method. Methods, transfer molding methods, injection molding methods, lotto molding methods, lotining molding methods, thermally induced phase separation methods, non-solvent induced phase separation methods, and the like can be employed.

The antibacterial material of the present invention is preferably a coating film because it can be applied to articles having various shapes. A coating film means the film | membrane obtained by apply | coating the coating composition containing the said fluorine-containing copolymer or the said fluorine-containing copolymer. Examples of the method for forming the coating film include spin coating, drop casting, dip nip, spray coating, brush coating, dipping, electrostatic coating, and inkjet printing. Of these, spin coating, drop casting, and dipping are preferred from the standpoint of simplicity.

The coating film is preferably obtained by applying a coating composition containing the fluorine-containing copolymer and an organic solvent. As the organic solvent, methanol, ethanol, 2-propanol, 2-butanol, 1-butanol, 1-hexanol, acetone, tetrahydrofuran, methyl ethyl ketone, dimethylacetamide, dimethylformamide and the like can be used. Of these, 2-butanol, 1-butanol, 1-hexanol, and tetrahydrofuran are preferable in that a transparent and uniform coating film can be easily obtained. From the viewpoint of solubility of the fluorinated copolymer, methanol, ethanol, 2-propanol, tetrahydrofuran, and dimethylformamide are preferable.

When the antibacterial material of the present invention is a coating film, the film thickness is preferably 0.1 to 50 μm, more preferably 0.5 to 30 μm, and further preferably 1.0 to 20 μm. preferable.

Since the antibacterial material of the present invention has excellent antibacterial properties, it can be applied to various articles that require antibacterial properties. As the article, contact lenses, toiletries, kitchen utensils, air conditioners, food factory equipment, sewage treatment plant equipment, drain pipes and the like are preferable. An antibacterial article comprising the antibacterial material of the present invention, which is a contact lens, toiletry product, kitchen watering device, air conditioner, food factory facility, sewage treatment plant facility, or drain pipe, is also provided in the present invention. It is one of.

Although the aspect which applies the antibacterial material of this invention to the said antibacterial article is not specifically limited, The antibacterial material of this invention is at least the said antibacterial property at the point which fully exhibits the antibacterial effect of the antibacterial material of this invention. It is preferable to apply so as to constitute the surface of the article.

The present invention is a method for inhibiting the growth of Escherichia coli on the surface of an article, characterized in that a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit is applied to the surface of the article. The fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit is —CH (OH) —CXY— (wherein X and Y are the same or different and each represents H, F or a fluoroalkyl group, provided that , At least one of X and Y is F or a fluoroalkyl group). For this reason, by applying the fluorine-containing copolymer to the surface of the article, the growth of E. coli on the surface of the article can be inhibited.

Moreover, it is thought that the E. coli growth inhibitory action of the fluorinated copolymer is derived not only from the fluoroalcohol structure but also from a hydrophilic / hydrophobic phase separation structure or a sea-island structure. The fluorine-containing copolymer has a structure derived from a hydrophobic fluorine-containing olefin (for example, —CF ₂ CF ₂ —) and a hydrophilic hydroxyl structure, and the hydrophobic structure and the hydrophilic structure are respectively It is presumed that they gathered together to form a hydrophilic / hydrophobic phase separation structure or sea-island structure.

The fluorine-containing copolymer is not particularly limited as long as it has a fluorine-containing olefin unit and a vinyl alcohol unit, but the fluorine-containing copolymer described as the fluorine-containing copolymer used in the antibacterial material of the present invention is not limited. It is preferable to use it.

Examples of the article include various articles that require antibacterial properties against Escherichia coli. Specifically, contact lenses, toiletries, kitchen watering devices, air conditioners, food factory equipment, sewage treatment plant equipment, drain pipes, and the like are preferable.

In the method of the present invention, the location to which the fluorine-containing copolymer is applied is not particularly limited as long as it is the surface of the article, but is preferably a location where E. coli is more likely to grow.

In the method of the present invention, the method for applying the fluorine-containing copolymer to the surface of the article is not particularly limited, and the article may be produced by molding the fluorine-containing copolymer. You may form the coating film which consists of the said fluorine-containing copolymer on the surface of the article | item consisting of.

Next, the present invention will be described with reference to examples. However, the present invention is not limited to such examples.

Each numerical value of the examples was measured by the following method.

[Measurement of fluorine-containing olefin unit content by fluorine content]
A 10 mg sample was burned by the oxygen flask combustion method, the decomposition gas was absorbed in 20 ml of deionized water, and the fluorine ion concentration in the absorbing solution was measured by the fluorine selective electrode method (mass%). The content (mol%) of the fluorine-containing olefin unit in the polymer was calculated from the fluorine content of the polymer before saponification.

[Measurement of alternating rate by NMR (nuclear magnetic resonance)]
¹ H-NMR measurement conditions: 400 MHz (tetramethylsilane = 0 ppm)

[Molecular weight and molecular weight distribution]
The average molecular weight was calculated from data measured by flowing tetrahydrofuran (THF) as a solvent at a flow rate of 1 ml / min by gel permeation chromatography (GPC).
RI was used for the detector, and a polystyrene standard sample was used for the calibration curve sample, and the measurement was performed at a flow rate of 1 ml / min and a sample injection amount of 200 μL.

[Measurement of degree of saponification by IR analysis]
Measurements were made at room temperature with a Fourier transform infrared spectrophotometer.

[Melting point (Tm)]
Using DSC (differential scanning calorimeter), the temperature corresponding to the maximum value in the heat of fusion curve when the temperature was raised (second run) at 10 ° C./min was defined as Tm (° C.).

[Decomposition temperature]
The decomposition temperature was the temperature at the inflection point that showed a significant weight loss in the thermal decomposition curve in the TGA (calorimeter) measurement. Specifically, in the TGA curve, the decomposition temperature was obtained by a method (intersection method) in which an auxiliary line was drawn before and after a large weight loss to obtain an intersection point.

[SEM measurement method]
Using a scanning electron microscope, the surface of the coating film was observed arbitrarily at three magnifications at 400 times and 2500 times.

The polymers used in the examples are shown in Table 1.

Example 1
A 0.1 wt% methanol solution of polymer P-1 was spin coated onto a PET film (1 cm × 1 cm) at room temperature. Specifically, 10 μL of the above solution was dropped on a PET film and rotated at 700 rpm for 10 seconds. Then, it dried under reduced pressure with the rotary vacuum pump at room temperature, and obtained the coating film (coating film formed in the surface of PET film).

About the obtained coating film | membrane, the antithrombogenicity (30 minutes) was evaluated with the following method. The results are shown in Table 2.

[Platelet adhesion and platelet activation (30 minutes)]
The obtained coating film was fixed to the bottom of a weighing bottle having a diameter of 3.3 cm with a small amount of silicon adhesive. This was washed 3 times with pure water and then immersed in phosphate buffered saline (PBS) for 12 hours. After removing PBS, 2.0 mL of platelet-rich plasma (PRP, platelet count: 2 × 10 ⁵ / μL) containing 0.1% sodium citrate diluted 3-fold with PBS was added to the weighing bottle at 37 ° C. For 30 minutes. PRP was removed and the coating membrane was washed 3 times with PBS. PBS containing 2% glutaraldehyde was added and allowed to stand at 4 ° C. for 2 hours to immobilize platelets adhered to the coating film surface. The sample was washed 3 times with PBS and once with pure water, and dried under reduced pressure overnight. The obtained sample was gold-coated with a gold sputtering apparatus, the surface of the coating film was observed arbitrarily at 3 magnifications using a scanning electron microscope at a magnification of 400 times, and the number of adhered platelets was counted. The case where the adherent platelets were spherical was regarded as not activated, and the case where aggregation, flattening or false feet were observed was regarded as activated.

Comparative Example 1
L104B (ethylene / vinyl alcohol molar ratio = 27/73) which is an ethylene-vinyl alcohol copolymer (EVOH) manufactured by Kuraray Co., Ltd. was dissolved in dimethyl sulfoxide at 60 ° C. 10 μL of the above solution was dropped on a PET film and rotated at 700 rpm for 10 seconds. Thereafter, the coating film was obtained by drying under reduced pressure with a rotary vacuum pump at 40 ° C. for 6 hours. About the obtained coating film | membrane, the antithrombogenicity (30 minutes) was evaluated by the method similar to Example 1. FIG. The results are shown in Table 2.

Comparative Examples 2-3
E105B (ethylene / vinyl alcohol molar ratio = 44/56, Comparative Example 2) or G156B (ethylene / vinyl alcohol molar ratio = 48/52), which is an ethylene-vinyl alcohol copolymer manufactured by Kuraray Co., Ltd. instead of L104B A coating film was obtained in the same manner as in Comparative Example 1 except that Example 3) was used. About the obtained coating film | membrane, the antithrombogenicity (30 minutes) was evaluated by the method similar to Example 1. FIG. The results are shown in Table 2.

Comparative Example 4
Antithrombogenicity (30 minutes) was evaluated in the same manner as in Example 1 except that a commercially available PET film was used as it was instead of the coating film. The results are shown in Table 2.

Example 2
A coating film was obtained in the same manner as in Example 1 except that the amount of the solution dropped onto the PET film was changed to 30 μL.

About the obtained coating film | membrane, the antithrombogenicity (1 hour) was evaluated with the following method. The results are shown in Table 3.

[Platelet adhesion and platelet activation (1 hour)]
The obtained coating film was fixed to the bottom of a weighing bottle having a diameter of 3.3 cm with a small amount of silicon adhesive. This was washed 3 times with pure water and then immersed in phosphate buffered saline (PBS) for 12 hours. After removing PBS, 2.0 mL of platelet-rich plasma (PRP, platelet count: 2 × 10 ⁵ / μL) containing 0.1% sodium citrate diluted 3-fold with PBS was added to the weighing bottle at 37 ° C. And left for 1 hour. PRP was removed and the coating membrane was washed 3 times with PBS. PBS containing 2% glutaraldehyde was added and allowed to stand at 4 ° C. for 2 hours to immobilize platelets adhered to the coating film surface. The sample was washed 3 times with PBS and once with pure water, and dried under reduced pressure overnight. The obtained sample was gold-coated with a gold sputtering apparatus, the surface of the coating film was observed arbitrarily at 3 magnifications using a scanning electron microscope at a magnification of 400 times, and the number of adhered platelets was counted. The case where the adherent platelets were spherical was regarded as not activated, and the case where aggregation, flattening or false feet were observed was regarded as activated.

Examples 3-5
Instead of polymer P-1, polymer P-2 (Example 3), polymer P-3 (Example 4) or polymer P-4 (Example 5) was used. A coating film was obtained. About the obtained coating film | membrane, the antithrombogenicity (1 hour) was evaluated by the method similar to Example 2. FIG. The results are shown in Table 3.

Comparative Example 5
Antithrombogenicity (1 hour) was evaluated in the same manner as in Example 2 except that a commercially available PET film was used as it was instead of the coating film. The results are shown in Table 3.

Example 6
A coating film was obtained in the same manner as in Example 1.

About the obtained coating film | membrane, the adhesiveness of colon_bacillus | E._coli was evaluated with the following method. The results are shown in Table 4. A scanning electron microscope (SEM) photograph at a magnification of 2500 times on the surface of the coating film in the evaluation of the adhesion of Escherichia coli is shown in FIG.

[Adhesiveness of E. coli]
The obtained coating film was fixed to the bottom of a 24-well cell culture dish with a small amount of silicon adhesive. This was washed 3 times with pure water and then immersed in phosphate buffered saline (PBS) for 12 hours. After the PBS was removed, a dispersion prepared at OD ₆₀₀ = 0.003 in Muller-Hinton II (MH) medium containing Escherichia coli (E. coli ATCC® 25922 ^™ ) in the logarithmic growth phase was prepared in the above cell culture dish. 2.0 mL was added and cultured at 37 ° C. for 20 hours. The supernatant was removed and the coating membrane was washed 3 times with PBS. PBS containing 2% glutaraldehyde was added and allowed to stand at 4 ° C. for 2 hours to immobilize E. coli adhering to the coating membrane surface. The sample was washed 3 times with PBS and once with pure water, and dried under reduced pressure overnight. The obtained sample was coated with gold using a gold sputtering apparatus, and the coating film surface was observed arbitrarily at three magnifications of 400 times and 2500 times using a scanning electron microscope to evaluate the adhesion and colony formation amount of E. coli.

Comparative Example 6
The adhesion of Escherichia coli was evaluated in the same manner as in Example 6 except that a commercially available PET film was used as it was instead of the coating film. The results are shown in Table 4. A scanning electron microscope (SEM) photograph at a magnification of 2500 times on the surface of the PET film in the evaluation of the adhesion of Escherichia coli is shown in FIG.

Claims (15)

An antithrombogenic material comprising a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit, wherein a content of the fluorine-containing olefin unit in the fluorine-containing copolymer is 30 to 60 mol%. 2. The antithrombogenic material according to claim 1, wherein an alternating ratio of the fluorine-containing olefin unit and the vinyl alcohol unit in the fluorine-containing copolymer is 10 to 100%. The antithrombogenic material according to claim 1 or 2, wherein the fluorine-containing olefin is at least one selected from the group consisting of tetrafluoroethylene, chlorotrifluoroethylene, and hexafluoropropylene. The antithrombogenic material according to claim 1, 2 or 3, wherein the fluorine-containing copolymer has a fluorine-containing olefin unit, a vinyl alcohol unit and a vinyl ester monomer unit. 5. The antithrombogenic material according to claim 1, wherein the fluorine-containing copolymer is a copolymer obtained by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit. 6. The antithrombotic material according to claim 1, which is a coating film. The antithrombotic material according to claim 1, 2, 3, 4, 5 or 6,
An antithrombotic article, which is a vial, an artificial blood vessel, a stent, a catheter, an artificial heart, an artificial lung, an artificial heart valve, or a blood storage bag. An antibacterial material comprising a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit, wherein a content of the fluorine-containing olefin unit in the fluorine-containing copolymer is 10 to 60 mol%. The antibacterial material according to claim 8, wherein an alternating rate of the fluorine-containing olefin unit and the vinyl alcohol unit in the fluorine-containing copolymer is 10 to 100%. The antibacterial material according to claim 8 or 9, wherein the fluorine-containing olefin is at least one selected from the group consisting of tetrafluoroethylene, chlorotrifluoroethylene, and hexafluoropropylene. The antibacterial material according to claim 8, 9 or 10, wherein the fluorine-containing copolymer has a fluorine-containing olefin unit, a vinyl alcohol unit and a vinyl ester monomer unit. The antibacterial material according to claim 8, 9, 10, or 11, wherein the fluorine-containing copolymer is a copolymer obtained by saponifying a copolymer having a fluorine-containing olefin unit and a vinyl ester monomer unit. The antibacterial material according to claim 8, 9, 10, 11, or 12, which is a coating film. The antibacterial material according to claim 8, 9, 10, 11, 12, or 13.
Antibacterial articles characterized by being contact lenses, toiletries, kitchen watering equipment, air conditioners, food factory equipment, sewage treatment plant equipment, or drain pipes. A method for inhibiting the growth of Escherichia coli on the surface of an article, wherein a fluorine-containing copolymer having a fluorine-containing olefin unit and a vinyl alcohol unit is applied to the surface of the article.