Microbial adhesion–suppressing resin and antibacterial / antiviral processed product

Abstract

The present invention provides: a microbial adhesion–suppressing resin that, even using a non-ionic copolymer, has at least the same or better microbial adhesion suppression properties compared to conventional polymers that have an ionic group such as a phosphorylcholine group; and an antibacterial / antiviral processed product that is coated with the microbial adhesion–suppressing resin. Moreover, the present invention provides: a microbial adhesion–suppressing resin that is non-ionic and therefore has stable microbial adhesion suppression properties that are unaffected by pH or salt concentration; and an antibacterial / antiviral processed product that is coated with the microbial adhesion–suppressing resin. This microbial adhesion–suppressing resin comprises a block copolymer that is formed from: a polymer (A) of monomers that include a monomer (a) represented by general formula (1); and a polymer (B) of monomers that include at least one monomer selected from the group consisting of monomers (b) represented by general formula (2) and general formulas (3)–(7) in the description.

Description

Microbial adhesion inhibitor resin and antibacterial and antiviral processed products

[0001] The present invention relates to a microbial adhesion-inhibiting resin and an antibacterial and antiviral processed product. This application claims priority to Japanese Patent Application No. 2023-029892, filed on February 28, 2023, the contents of which are incorporated herein by reference.

[0002] The COVID-19 pandemic has sparked growing interest in antibacterial and antiviral agents and processed products. Traditionally, antibacterial and antiviral agents and processed products were primarily used to prevent infection in patients with weakened immune systems, such as those in medical and nursing care settings. However, the spread of COVID-19 has led to widespread use in homes, public transportation, commercial facilities, companies, and factories. While most current antibacterial and antiviral processed products inactivate bacteria and viruses by damaging them, inactivated bacteria and viruses remain on the product surface. Furthermore, if additional bacteria or viruses adhere to the inactivated bacteria or viruses, they will remain active and multiply without coming into contact with the antibacterial and antiviral surface, forming a biofilm that cannot be controlled with chemicals.

[0003] Polymers having phosphorylcholine groups used in the prior art have low protein adsorption properties (for example, Patent Document 1, etc.) and also have the effect of reducing microbial adhesion (for example, Patent Document 2, etc.).

[0004] Japanese Patent Application Publication No. 7-83923 Special Publication No. 7-506138

[0005] However, the polymers having phosphorylcholine groups disclosed in Patent Documents 1 and 2 have ionic groups (cations and anions), and therefore there is a concern that the ability to inhibit adhesion of microorganisms may be impaired.

[0006] The present invention has been made to solve the above-mentioned problems, and aims to provide a microbial adhesion-inhibiting resin and an antibacterial and antiviral processed product that have microbial adhesion-inhibiting properties similar to or superior to those of conventional polymers having ionic groups such as phosphorylcholine groups, even when a nonionic copolymer is used. Furthermore, because the microbial adhesion-inhibiting resin and antibacterial and antiviral processed product of the present invention are nonionic, they are expected to have stable microbial adhesion-inhibiting properties that are not affected by pH or salt concentration.

[0007] The present disclosure includes the following embodiments: [1] A microbial adhesion-inhibiting resin comprising a block copolymer composed of a polymer (A) of a monomer including a monomer (a) represented by the following general formula (1) and a polymer (B) of a monomer including one or more monomers selected from the group consisting of monomers (b) represented by the following general formulas (2) to (7): (In formulas (1) to (7), R ０ is an alkyl group having 1 to 3 carbon atoms, R １ is a hydrogen atom or a methyl group, R ２ , R ７ are each independently an alkylene group having 2 to 3 carbon atoms, R ３ , R ４ , R ５ , R ６ are each independently a hydrogen atom or an alkyl group having 1 to 2 carbon atoms, and X is —CO ２ － , -SO ３ － , -OSO ３ － , -OSO ２ － , -OP(=O)(OR ８ ) O － , -OP(=O)(R ８ ) O － , -P(=O)(OR ８ ) O － , -P(=O)(R ８ ) O － a monovalent anion selected from the group consisting of８ is an alkyl group having 1 to 3 carbon atoms, and n is an integer from 1 to 9.) [2] The microbial adhesion-inhibiting resin according to [1], wherein in the block copolymer, the molar ratio (A:B) of the polymer (A) to the polymer (B) is 1:50 to 50:1. [3] The microbial adhesion-inhibiting resin according to [1] or [2], wherein the block copolymer is a triblock copolymer, a diblock copolymer, or a multi-branched block copolymer. [4] The microbial adhesion-inhibiting resin according to any one of [1] to [3], wherein in the block copolymer, the degree of polymerization of the polymer (A) is 30 to 3,000, and the degree of polymerization of the polymer (B) is 20 to 20,000. [5] The microbial adhesion-inhibiting resin according to any one of [1] to [4], wherein in the block copolymer, the copolymerization ratio of the monomer (b) to the monomer (a) is 99 / 1 to 10 / 90 by molar ratio. [6] An antibacterial and antiviral processed product coated with the microbial adhesion-inhibiting resin according to any one of [1] to [5].

[0008] According to the present invention, it is possible to provide a microbial adhesion-inhibiting resin that has microbial adhesion-inhibiting properties similar to or superior to those of conventional polymers having ionic groups such as phosphorylcholine groups, even when a nonionic copolymer is used, and to provide antibacterial and antiviral products coated with the microbial adhesion-inhibiting resin. Furthermore, because the microbial adhesion-inhibiting resin of the present invention is nonionic, it is possible to provide a microbial adhesion-inhibiting resin that has stable microbial adhesion-inhibiting properties without being affected by pH or salt concentration, and an antibacterial and antiviral product coated with the microbial adhesion-inhibiting resin.

[0009] FIG. 1 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Example 1-1. FIG. 2 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Example 1-2. FIG. 3 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Example 1-3. FIG. 4 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Example 1-4. FIG. 5 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Example 1-5. FIG. 6 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Example 1-6. FIG. 7 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Example 1-7. FIG. 1 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Comparative Example 1-1. FIG. 2 is an SEM photograph of the number of bacteria adhering to a surface in the microbial adhesion inhibition test of Comparative Example 1-2. FIG. 1 is an SEM photograph of the number of bacteria adhering to a surface in a microbial adhesion inhibition test of Comparative Example 1-3. FIG. 2 is an SEM photograph of the number of bacteria adhering to a surface in a microbial adhesion inhibition test of Example 1-8. FIG. 3 is an SEM photograph of the number of bacteria adhering to a surface in a microbial adhesion inhibition test of Comparative Example 1-4. FIG. 4 is an SEM photograph of the number of bacteria adhering to a surface in a microbial adhesion inhibition test of Example 1-9. FIG. 5 is an SEM photograph of the number of bacteria adhering to a surface in a microbial adhesion inhibition test of Comparative Example 1-5.

[0010] The present invention will be described in further detail below, but the present invention is not limited to the following embodiments.

[0011] "To" means greater than or equal to the value before "To" and less than or equal to the value after "To". "(Meth)acrylic" is a general term for acrylic and methacrylic, and "(meth)acrylate compound (B)" is a general term for acrylate compounds and methacrylate compounds. "(Meth)acrylic acid" is a general term for acrylic acid and methacrylic acid.

[0012] (Microbial Adhesion-Inhibiting Resin) A microbial adhesion-inhibiting resin according to one embodiment of the present invention (sometimes referred to as the microbial adhesion-inhibiting resin of this embodiment) comprises a block copolymer composed of a polymer (A) of a monomer containing a monomer (a) represented by the general formula (1) above, and a polymer (B) of a monomer containing one or more monomers selected from the group consisting of monomers (b) represented by the general formulas (2) to (7) above. The molar ratio (A:B) of the polymer (A) to the polymer (B) is preferably 1:50 to 50:1.

[0013] [Monomer (a)] The monomer (a) used in the present invention is the monomer (a) represented by the above general formula (1). ０ is an alkyl group having 1 to 3 carbon atoms, R １ is a hydrogen atom or a methyl group, R ２ is an alkylene group having 2 to 3 carbon atoms.

[0014] The use of monomer (a) improves the film-forming ability of the copolymer and adhesion to the substrate, allowing for a wider range of thickness control to obtain a smoother coating film, and the coating film surface has the ability to inhibit microbial adhesion.

[0015] Among the monomers (a) represented by the general formula (1), compounds in which n is 1 to 3 are preferred, and 2-methoxyethyl acrylate, 2-ethoxyethyl acrylate, methyl carbitol acrylate, 2-(2-ethoxyethoxy)ethyl acrylate, ethyl carbitol acrylate, methoxytriethylene glycol acrylate, and ethoxytriethylene glycol acrylate are more preferred, with 2-methoxyethyl acrylate, 2-ethoxyethyl acrylate, and 2-(2-ethoxyethoxy)ethyl acrylate being particularly preferred. The polymer (A) in the present invention is a polymer obtained by polymerizing only the monomers (a).

[0016] Monomers that can be used other than the monomer (a) include monomers represented by the following formulas (2) to (7) and (meth)acrylic monomers having functional groups such as a hydroxyl group, a glycidyl group, an isocyanato group, a carboxyl group, an amino group, and a sulfonic acid group.

[0017] [Monomer (b)] The monomer (b) used in the present invention is (meth)acrylamide and / or a derivative thereof (N- or N,N-substituted (meth)acrylamide). Particularly preferably, the acrylamide-based monomers of the above formulas (2) to (7) are used.

[0018] In the formulas (2) to (7), R １ is a hydrogen atom or a methyl group, and R ２ , R ７ are each independently an alkylene group having 2 to 3 carbon atoms, and R ３ , R ４ , R ５ , R ６ are each independently a hydrogen atom or an alkyl group having 1 to 2 carbon atoms, and X is —CO ２ － , -SO ３ － , -OSO ３ － , -OSO ２ － , -OP(=O)(OR ８ ) O － , -OP(=O)(R ８ ) O － , -P(=O)(OR ８ ) O － , -P(=O)(R ８ ) O － and R is a monovalent anion selected from ８ is an alkyl group having 1 to 3 carbon atoms, and n is an integer from 1 to 9.

[0019] By using monomer (b), the resulting block copolymer has good solubility or dispersibility in water, high stability, and good film-forming ability, resulting in a smoother coating film. Furthermore, when N,N-dimethylacrylamide is used as monomer (b), the resulting coating film surface has particularly excellent microbial adhesion inhibitory properties, making it suitable for antibacterial and antiviral processed products.

[0020] [Polymer (B)] Polymer (B) is a polymer containing monomer (b), and polymer (B) may be a polymer composed of monomer (b) represented by any of the general formulae (2) to (7) above, or a copolymer with other monomers. Monomer (a) is preferably used as the other monomer used in the copolymer. The ratio (molar ratio) of monomer (b) to monomer (a) is 99:1 to 10:90, more preferably 95:5 to 30:70, even more preferably 90:10 to 50:50, and particularly preferably 90:10 to 60:40. A copolymer composed of such monomer (b) and monomer (a) also has the advantage that it allows for easier synthesis of block copolymers.

[0021] Furthermore, in the polymer (B) or copolymer (B), in addition to the monomers represented by the general formulae (1) to (7), other copolymerizable monomers can be used in combination, if necessary, to adjust the balance of hydrophilicity / hydrophobicity of the block copolymer or to impart functional groups to further reduce interaction with proteins. For example, acrylic monomers having an anionic group such as a sulfonic acid group or a carboxyl group, acrylic monomers having a cationic group such as a quaternary ammonium group, acrylic monomers having a zwitterionic group containing a quaternary ammonium group and a phosphate group, acrylic monomers having an amino acid residue containing a carboxyl group and an amino group, acrylic monomers having a sugar residue, acrylic monomers having a hydroxyl group, acrylic monomers having polyethylene glycol or polypropylene glycol chains, amphiphilic acrylic monomers having both a hydrophilic chain such as polyethylene glycol and a hydrophobic group such as nonylphenyl, polyethylene glycol diacrylate, N,N'-methylenebisacrylamide, and the like can be used in combination.

[0022] [Aspects of Block Copolymer] In the block copolymer according to this embodiment, the molar ratio (A:B) of the polymer (A) to the polymer (B) may be 1:50 to 50:1. The block copolymer may be a triblock copolymer, a diblock copolymer, or a multi-branched block copolymer. In the block copolymer according to this embodiment, the arrangement of the polymers (A) and (B) is not necessarily limited as long as it exhibits the above-described properties, and may be, for example, an A-B type, an A-B-A type, a B-A-B type, or a [B-A] type. ｐ (p is the number of branches of B, which is 3 to 10) are preferably used. Among these, AB type, A-B-A type, [BA] ｐ The multi-branched type is more preferred, and the AB type and ABA type are most preferred. ｐ The multi-branched type refers to the structure shown in the following example.

[0023] [B-A] ４ Type

[0024] The molar ratio (A:B) of component A to component B in the block copolymer according to this embodiment is preferably in the range of 1:60 to 60:1, more preferably in the range of 1:20 to 20:1, and most preferably in the range of 1:20 to 1:1. When the molar ratio of A to B is within this range, the resulting block copolymer has good solubility or dispersibility in water and high stability, and the copolymer has good film-forming ability, resulting in a smoother coating film. Furthermore, the coating film surface has the ability to inhibit microbial adhesion, which is preferable.

[0025] In the A-B-A type block copolymer, the degree of polymerization of A is preferably in the range of 30 to 3,000 and the degree of polymerization of B is preferably in the range of 20 to 20,000, more preferably in the range of 100 to 1,000 and 100 to 5,000, and particularly preferably in the range of 100 to 500 and 200 to 2,000. When the degrees of polymerization are in these ranges, the resulting block copolymer has good solubility or dispersibility in water, making it easy to prepare an aqueous paint, and also has good film-forming ability and inhibits microbial adhesion on the surface of the resulting coating film, which is preferable.

[0026] [Method for Synthesizing Block Copolymer] The block copolymer according to this embodiment can be produced by any method as long as the monomers (a) and (b) are polymerized to synthesize a block copolymer consisting of a polymer (A) and a polymer (B). Examples of known and commonly used polymerization methods include the following first and second methods. The first method is a method in which the monomer (a) is first subjected to living radical polymerization using an azo compound and / or organic peroxide as a radical polymerization initiator in the presence of a chain transfer agent (hereinafter referred to as a RAFT agent) such as trithiocarbonate, and the resulting polymer (A) is then subjected to living radical polymerization of the monomer (b). The second method is a method for synthesizing a block copolymer in which the monomer (b) is radically polymerized in the presence of an organic halide and a transition metal complex, and then the monomer (a) is added and radically polymerized.

[0027] In particular, the following methods (1-1) to (2-2) among known living radical polymerization methods are preferred as the method for synthesizing the block copolymer according to this embodiment. (1-1) In the first method, a RAFT agent and a monomer (a) are first polymerized in the presence of a small amount of a polymerization initiator, followed by isolation and purification to synthesize a macro RAFT agent consisting solely of polymer (A). The macro RAFT agent and a monomer (b) are then polymerized in the presence of a small amount of a polymerization initiator to obtain a block copolymer. (1-2) In the second method, a polymer terminal halide is first polymerized in the presence of an organic halide and a transition metal complex, followed by isolation and purification to synthesize a polymer terminal halide consisting solely of polymer (B). The polymer terminal halide is then polymerized with monomer (a) in the presence of a transition metal complex to obtain a block copolymer. (2-1) A method in which, in the first method, a RAFT agent and monomer (a) are polymerized in the presence of a small amount of polymerization initiator, and then monomer (b) is added without isolation to obtain a block copolymer. (2-2) A method in which, in the second method, monomer (b) is polymerized in the presence of an organic halide and a transition metal complex, and then monomer (a) is added without isolation to obtain a block copolymer. In the methods (2-1) and (2-2), it is not necessary to wait until the first monomer is completely consumed before adding the next monomer; the next monomer can be added when the conversion rate of the first monomer reaches about 65% or more. The polymer obtained in this case is not a complete block copolymer, but a so-called tapered block copolymer in which monomer (a) and monomer (b) are partially mixed. However, by appropriately selecting the ratio of monomer (a) to monomer (b), a copolymer with functionality equivalent to that of a complete block copolymer can be obtained.

[0028] In the present embodiment, in order to obtain a block copolymer in which the polymer (B) is a copolymer of the monomer (a) and the monomer (b), in addition to the above methods (2-1) and (2-2), a method of polymerizing a mixture of the monomer (a) and the monomer (b) can be used.

[0029] [Polymer Solution] The solvent used in the polymer solution containing the microbial adhesion-inhibiting resin of this embodiment is water, an organic solvent, or a mixture thereof. The type and concentration of the solvent used will vary depending on the composition and molecular weight of the resulting block copolymer and the type and surface properties of the substrate to be coated. More preferably, a solvent with a solvent concentration of 99.95 to 90% by mass containing ethanol, methanol, or isopropanol, which has excellent volatility and low invasiveness to the substrate, is used. Furthermore, when the microbial adhesion-inhibiting resin of the present invention is used as an aqueous solution, it is desirable to use a surfactant in combination or to subject the substrate surface to hydrophilization treatment such as ultraviolet / ozone treatment, corona treatment, or plasma treatment to improve adhesion to the substrate.

[0030] (Antibacterial and Antiviral Treated Product) An antibacterial and antiviral treated product according to one embodiment of the present invention (antibacterial and antiviral treated product of this embodiment) is a product coated with the microbial adhesion-inhibiting resin of this embodiment. Examples of products to be treated with the antibacterial and antiviral treatment include medical devices and nursing care tools. Examples of medical devices include catheters, tubes, wound dressings, contact lenses, respiratory masks, and hypodermic needles. Examples of products to be treated with the antibacterial and antiviral treatment include tools and devices with touch points that are touched by many users in homes, public transportation, commercial facilities, companies, and factories. Examples of products to be treated with the antibacterial and antiviral treatment include tables, chairs, doorknobs, handrails, switches, bathtubs, faucets, toilets, washbasins, kitchens, and water purification filters in homes. Examples of products to be treated with the antibacterial and antiviral treatment include handrails, straps, and chairs in public transportation. Examples of products to be treated with the antibacterial and antiviral treatment include general consumer goods such as food packaging, beverage containers, tableware, and clothing.

[0031] The antibacterial and antiviral treatment of this embodiment is characterized in that a variety of materials can be used as the surface material for coating with the microbial adhesion-inhibiting resin. For example, polyolefin resins such as polypropylene and polyethylene, polystyrene, polycarbonate, polyvinyl chloride, polyurethane, polyester, polysulfone, and polytetrafluoroethylene are used. Materials such as glass, ceramic, and metal are also suitable. Furthermore, a uniform coating film can be formed on substrates of any shape or form, including plates, sheets, straws, fibers, spheres, nonwoven fabrics, and porous materials. Materials such as glass and metal are also suitable. The coating film can be formed on substrates of any shape, including plates, sheets, straws, threads, and spheres.

[0032] The antibacterial and antiviral processed product of this embodiment only needs to have adhesion inhibitory properties against microorganisms including bacteria and viruses. Examples of bacteria include gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and gram-positive bacteria such as Staphylococcus aureus, Bacillus subtilis, and methicillin-resistant Staphylococcus aureus. Examples of viruses include enveloped influenza viruses, coronaviruses, and non-enveloped noroviruses and adenoviruses.

[0033] Next, the present invention will be described in more detail with reference to examples and comparative examples, but the present invention should not be limited to these. In the examples, all parts and percentages are by mass unless otherwise specified.

[0034] Synthesis Example 1 Synthesis of Block Copolymer P1 52.06 g of 2-methoxyethyl acrylate (MEA; manufactured by Toagosei Co., Ltd.) as monomer (a), 0.583 g of 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (Sigma-Aldrich) as a RAFT agent, 0.041 g of 2,2′-azobisisobutyronitrile, 226 g of tert.butanol, and 34 g of water were subjected to nitrogen bubbling for 1 hour with stirring, and then the mixture was reacted at 70° C. for 25 hours under a nitrogen stream to obtain 312 g of a mixed solution of a homopolymer of 2-methoxyethyl acrylate (polyMEA). Next, 21.6 g of the above polyMEA mixed solution, 19.7 g of N,N-dimethylacrylamide (DMAA; manufactured by KJ Chemicals Co., Ltd.) as monomer (b), 0.018 g of 2,2′-azobisisobutyronitrile, 68.5 g of tert-butanol, and 10 g of water were mixed with stirring and nitrogen bubbling for 1 hour, and then reacted at 70° C. for 17 hours under a nitrogen stream to obtain a mixed solution of AB type block copolymer P1 of the present invention consisting of 250 mol of monomer (a) and 1,500 mol of monomer (b). The mixture was dissolved in tetrahydrofuran, and the contents of monomer (a) and monomer (b) were measured using gas chromatography (GC; Agilent Technologies 7890B GC system) equipped with a Phenomenex ZB-WAX column (length 30 m, inner diameter 0.25 mm, film thickness 0.25 μm). The conversion rates of each were calculated from the results, and the conversion rates of monomer (a) and monomer (b) were 100% and 99%, respectively. The structure of block copolymer P1 was identified as shown by the following formula (9). Furthermore, the weight average molecular weight (Mw), number average molecular weight (Mn), and polydispersity (Mw / Mn) were measured using gel permeation chromatography (GPC; Tosoh Corporation HLC-8220 GPC system), and the results are shown in Table 1.

[0035]

[0036] Synthesis Example 2 [Synthesis of Block Copolymer P2] 26.0 g of the polyMEA mixed solution obtained in Example 1, 11.88 g of N,N-dimethylacrylamide (manufactured by KJ Chemicals Co., Ltd.) as monomer (b), 0.018 g of 2,2'-azobisisobutyronitrile, 68.5 g of tert.butanol, and 10 g of water were stirred and bubbled with nitrogen for 1 hour, followed by reaction for 17 hours at 70°C under a nitrogen stream to obtain a mixed solution of AB block copolymer P2 of the present invention consisting of 250 mol of monomer (a) and 750 mol of monomer (b). The mixed solution of AB block copolymer P2 of the present invention was subjected to GC measurement in the same manner as in Synthesis Example 1. The conversion of monomer (a) was 100% and the conversion of monomer (b) was 99%. The structure of block copolymer P2 was identified as shown in formula (10) below. The results of GPC measurement are shown in Table 1.

[0037]

[0038] Synthesis Example 3 [Synthesis of Block Copolymer P3] 15.6 g of the polyMEA mixed solution obtained in Example 1, 20.3 g of acryloylmorpholine (ACMO; manufactured by KJ Chemicals Co., Ltd.) as monomer (c), 0.018 g of 2,2'-azobisisobutyronitrile, 70.6 g of tert. butanol, and 10.6 g of water were stirred and bubbled with nitrogen for 1 hour, and then reacted at 70°C for 17 hours under a nitrogen stream to obtain a mixed solution of AB type block copolymer P3 of the present invention consisting of 250 mol of monomer (a) and 1,500 mol of monomer (c). GC measurement of the mixed solution of AB type block copolymer P3 of the present invention was performed in the same manner as in Synthesis Example 1. The conversion of monomer (a) was 100% and the conversion of monomer (c) was 98%. The structure of block copolymer P3 was identified as shown in formula (11) below. The results of GPC measurement are shown in Table 1.

[0039]

[0040] Synthesis Example 4 [Synthesis of Block Copolymer P4] 13.0 g of the polyMEA mixed solution obtained in Synthesis Example 1, 15.2 g of N,N-diethylacrylamide (DEAA; manufactured by Tokyo Chemical Industry Co., Ltd.) as monomer (d), 0.04 g of 2,2'-azobisisobutyronitrile, 53.0 g of tert.butanol, and 8.0 g of water were stirred while bubbling with nitrogen for 1 hour, and then reacted for 24 hours at 70°C under a nitrogen stream to obtain a mixed solution of AB-type block copolymer P4 of the present invention consisting of 250 mol of monomer (a) and 1,500 mol of monomer (d). GC measurement of the mixed solution of AB-type block copolymer P4 of the present invention was performed in the same manner as in Synthesis Example 1. The conversion of monomer (a) was 100% and the conversion of monomer (d) was 84%. The structure of block copolymer P4 was identified as shown in formula (12) below. The results of GPC measurement are shown in Table 1.

[0041]

[0042] Synthesis Example 5 Synthesis of Block Copolymer P5 18.8 g of 2-(2-ethoxyethoxy)ethyl acrylate (EEEA; manufactured by Tokyo Chemical Industry Co., Ltd.) as monomer (e), 0.146 g of 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (Sigma-Aldrich) as a RAFT agent, 0.026 g of 2,2′-azobisisobutyronitrile, 65.4 g of tert.butanol, and 10 g of water were subjected to nitrogen bubbling for 1 hour with stirring, and then the mixture was reacted at 70° C. for 25 hours under a nitrogen stream to obtain a mixed solution of a homopolymer of 2-(2-ethoxyethoxy)ethyl acrylate (polyEEEA). Next, 18.8 g of the above polyEEEA mixed solution, 11.9 g of N,N-dimethylacrylamide (manufactured by KJ Chemicals Co., Ltd.) as monomer (b), 0.027 g of 2,2'-azobisisobutyronitrile, 68.5 g of tert.butanol, and 10 g of water were mixed with stirring and nitrogen bubbling for 1 hour, followed by reaction for 17 hours at 70°C under a nitrogen stream to obtain a mixed solution of AB block copolymer P5 of the present invention consisting of 250 mol of monomer (e) and 1,500 mol of monomer (b). The mixed solution of AB block copolymer P5 of the present invention was subjected to GC measurement in the same manner as in Synthesis Example 1. The conversion of monomer (e) was 85% and the conversion of monomer (b) was 95%. The structure of block copolymer P5 was identified as shown by formula (13) below. The results of GPC measurement are shown in Table 1.

[0043] (Synthesis Example 6) [Synthesis of RAFT Agent] According to the non-patent document "Macromolecules, 35, 6754 (2002)," a RAFT agent "2-(1-Carboxy-1-methylethylsulfanylthiocarbonylsulfanyl)-2-methylpropionic acid" was synthesized by the following procedure. 2.62 g of acetone, 5.38 g of trichloromethane, 0.12 g of tetrabutylammonium hydrogen sulfate, 1.37 g of carbon disulfide, and 10.1 g of 50% sodium hydroxide were added to 6 mL of hexane, and the mixture was stirred for 5 hours and then allowed to stand overnight, resulting in the entire reaction solution solidifying. 45 mL of water was added to dissolve the solid, and then 6 mL of concentrated hydrochloric acid was added and the mixture was bubbled with nitrogen, resulting in the formation of a precipitate. This precipitate was filtered off, washed with water, and then dried. Recrystallization from a 60% aqueous acetone solution yielded 934 mg of pale yellow crystals. The structure of the RAFT agent was identified as shown in formula (14) below by C-NMR (JNM-LA300, manufactured by JEOL Ltd.).

[0044]

[0045] Synthesis Example 7 Synthesis of Block Copolymer P6 5.84 g of 2-methoxyethyl acrylate (manufactured by Toagosei Co., Ltd.) as monomer (a), 0.0254 g of the above-synthesized "2-(1-Carboxy-1-methylethylsulfanylthiocarbonylsulfanyl)-2-methylpropionic acid" as a RAFT agent, 0.0014 g of 2,2'-azobisisobutyronitrile, 25.4 g of tert.butanol, and 3.8 g of water were stirred with nitrogen bubbling for 1 hour, and then reacted at 70°C for 20 hours under a nitrogen stream. Next, 13.3 g of N,N-dimethylacrylamide (KJ Chemicals Co., Ltd.) as monomer (b), tert. 57.9 g of butanol and 8.6 g of water were added, and the mixture was further stirred at 70° C. for 24 hours to obtain a mixed solution of the ABA block copolymer P6 of the present invention, which is composed of 500 mol of monomer (a) and 1,500 mol of monomer (b).

[0046] The mixed solution of the ABA block copolymer 6 of the present invention was subjected to GC analysis in the same manner as in Synthesis Example 1. The conversion of monomer (a) was 100% and the conversion of monomer (b) was 99%. The structure of block copolymer P6 was identified as shown in formula (15) below. The results of GPC analysis are shown in Table 1.

[0047]

[0048] The theoretical molecular weights of polymer (A), polymer (B), and the block copolymer were calculated from the conversion rates using the following formula: As a result, in the A-B-A block copolymer, the theoretical molecular weight Mn of polymer (A) was approximately 32,500 (250 mol), the theoretical molecular weight Mn of polymer (B) was approximately 148,000 (1,480 mol), and the theoretical molecular weight Mn of block copolymer P1 was approximately 213,000.

[0049]

[0050] Comparative Synthesis Example 1 Polymer cP1 was synthesized as follows using 2-methacryloyloxyethyl phosphorylcholine (MPC; manufactured by Tokyo Chemical Industry Co., Ltd.) and n-butyl methacrylate (BMA; manufactured by Tokyo Chemical Industry Co., Ltd.) as monomers according to the method described in Patent Document 1 (JP-A-7-83923, WO 1993 / 01221).

[0051] 1.772 g of MPC and 1.991 g of BMA were weighed into a glass polymerization reaction tube, to which 0.0328 g of 2,2'-azobisisobutyronitrile as a polymerization initiator and 20 ml of methanol as a polymerization solvent were added. After thoroughly replacing the atmosphere inside the reaction tube with argon, the tube was sealed and heated to 60°C for 24 hours to carry out the polymerization reaction. The resulting reaction mixture was ice-cooled and then added dropwise to 400 ml of diethyl ether to precipitate the polymer. The polymer was filtered, thoroughly washed with diethyl ether, and dried under reduced pressure to obtain 2.035 g of a white powdery polymer. A tetrahydrofuran solution of the resulting polymer was analyzed using GPC, and the molecular weight was measured to be 29,000 in terms of polystyrene.

[0052]

[0053] Example 1-1 [Preparation of a microbial adhesion-inhibitory resin coating] The block copolymer P1 obtained in Synthesis Example 1 above was dissolved in ethanol as the microbial adhesion-inhibitory resin of the present invention to obtain a polymer solution L1 with a coating concentration of 0.5% by mass. The polymer solution L1 was then thinly coated on a PEN (polyethylene naphthalate) film whose surface had been treated with ultraviolet light and ozone, and then dried to obtain a PEN film F1 having a microbial adhesion-inhibitory resin coating.

[0054] [Test for evaluating microbial adhesion inhibitory properties] The surface of the PEN film F1 having the microbial adhesion inhibitory resin coating film was coated with 1 × 10 ６ 100 μl of bacteria (E. coli) prepared at a concentration of bacteria / ml was placed on the plate. After 24 hours, the medium was removed, the plate was washed with saline, and then glutaraldehyde solution was placed on the plate and allowed to stand for 1 hour for fixation. After fixation, the plate was washed with pure water and the bacteria adhering to the surface were observed using SEM (Figure 1). The number of bacteria was counted in images observed at 1500x magnification, and the number of attached bacteria was calculated as the average of two fields of view (two images). The results are shown in Table 2. The glutaraldehyde solution was prepared by adjusting glutaraldehyde (Kanto Chemical, 25% glutaraldehyde solution for electron microscopy) to a concentration of 1% in phosphate-buffered saline (Fujifilm Wako Pure Chemical Industries, D-PBS(-)).

[0055] <Scanning Electron Microscope (SEM) Measurement Conditions, etc.> Apparatus: TM4000PlusII manufactured by Hitachi High-Tech Corporation Measurement conditions: Charge reduction mode, secondary electron detector Magnification: 1500x

[0056] Examples 1-2 to 1-6 PEN films F2 to F6 having microbial adhesion-inhibitory resin coatings were obtained in the same manner as in Example 1-1, except that block copolymers P2 to P6 were used. The PEN films F2 to F6 were then tested for their microbial adhesion-inhibitory properties in the same manner as in Example 1-1. The results are shown in Figures 2 to 6 and Table 2.

[0057] Example 1-7 A PEN film F7 having a microbial adhesion-inhibiting resin coating was obtained in the same manner as in Example 1-1, except that polymer solution L2 having a coating concentration of 0.1% by mass of the block copolymer P6 was used. A microbial adhesion-inhibiting test for PEN film F7 was then conducted in the same manner as in Example 1-1. The results are shown in Figure 7 and Table 2.

[0058] Comparative Example 1-1 A PEN film cF1 having a microbial adhesion-inhibitory resin coating was obtained in the same manner as in Example 1-1, except that the polymer cP1 obtained in Comparative Synthesis Example 1 was used. A microbial adhesion-inhibitory ability evaluation test of the PEN film cF1 was then carried out in the same manner as in Example 1-1. The results are shown in FIG. 8 and Table 2.

[0059] Comparative Example 1-2 A PEN film cF2 having a microbial adhesion-inhibiting resin coating was obtained in the same manner as in Example 1-7, except that the polymer cP1 obtained in Comparative Synthesis Example 1 was used. The microbial adhesion-inhibiting ability of the PEN film cF2 was then evaluated in the same manner as in Example 1-1. The results are shown in FIG. 9 and Table 2.

[0060] Comparative Example 1-3 A PEN film cF3 not having a microbial adhesion-inhibiting resin coating was obtained in the same manner as in Example 1-1, except that polymer-free ethanol was used instead of the polymer solution L1. A microbial adhesion evaluation test for the PEN film cF3 was then carried out in the same manner as in Example 1-1. The results are shown in FIG. 10 and Table 2.

[0061]

[0062] Example 1-8 A test to evaluate the microbial adhesion inhibitory properties of PEN film F6 was carried out in the same manner as in Example 1-6, except that the LB medium (pH 7) in Example 1-6 was adjusted to pH 5 by adding 1N-HCl (Kanto Chemical). The results are shown in Figure 11 and Table 3.

[0063] Comparative Example 1-4 A test to evaluate the microbial adhesion inhibitory properties of PEN film cF1 was carried out in the same manner as in Example 1-1, except that the LB medium (pH 7) of Comparative Example 1-1 was adjusted to pH 5 by adding 1N-HCl (Kanto Chemical). The results are shown in FIG. 12 and Table 3. ​

[0064]

[0065] Example 1-9 A test to evaluate the microbial adhesion inhibitory ability of PEN film F6 was carried out in the same manner as in Example 1-6, except that NaCl was added to the LB medium (NaCl concentration: 1% by mass) in Example 1-6 to adjust the NaCl concentration to 2% by mass. The results are shown in Figure 13 and Table 4.

[0066] Comparative Example 1-5 A test to evaluate the microbial adhesion inhibitory ability of PEN film cF1 was carried out in the same manner as in Example 1-1, except that NaCl was added to the LB medium (NaCl concentration: 1% by mass) of Comparative Example 1-1 to adjust the NaCl concentration to 2% by mass. The results are shown in Figure 14 and Table 4.

[0067]

[0068] (Examples 2-1 and 2-2, Comparative Examples 2-1 to 2-3) Tests to evaluate microbial adhesion inhibition were conducted in the same manner as in Examples 1-7 and 1-6 and Comparative Examples 1-2, 1-1, and 1-3, respectively, except that the bacteria used in the culture medium in which the bacteria were suspended was Staphylococcus aureus. The results are shown in Table 5.

[0069] (Example 3-1, Comparative Examples 3-1 and 3-2) Tests to evaluate microbial adhesion inhibition were conducted in the same manner as in Example 1-6, Comparative Example 1-1, and Comparative Example 1-3, respectively, except that the bacteria used in the medium in which the bacteria were suspended was Pseudomonas aeruginosa. The results are shown in Table 6.

[0070] (Discussion) From the results in Tables 2, 5, and 6 above, it was found that films treated with the microbial adhesion-inhibiting resin of the present invention have microbial adhesion-inhibiting properties against both gram-positive and gram-negative bacteria. Furthermore, at the same coating concentration (0.5% by mass), superior microbial adhesion-inhibiting properties were observed compared to the polymer of Patent Document 1. In particular, as shown in Table 2, a comparison between Example 1-7 and Comparative Example 1-1 revealed that the resin had superior microbial adhesion-inhibiting properties compared to the polymer of Patent Document 1, even at a coating concentration one-fifth lower.

[0071] ​​​From the above results, it was found that the microbial adhesion-inhibiting resin of the present invention, even when a nonionic copolymer is used, has microbial adhesion-inhibiting properties similar to or better than those of conventional polymers having ionic groups such as phosphorylcholine groups. Furthermore, because the biofouling-inhibiting resin of the present invention is nonionic, it can be expected to have stable microbial adhesion-inhibiting properties without being affected by pH or salt concentration. It is thought that the mechanism by which the microbial adhesion-inhibiting resin of the present invention inhibits microbial adhesion may be different from that of conventional polymers having ionic groups. For example, it is thought that because the water molecules surrounding the nonionic polymer form a stable hydrated structure and have no electric charge, microorganisms cannot recognize the material surface, resulting in adhesion inhibition.

[0072] The following can be inferred from the results in Table 3. Because polymer cP1 is zwitterionic, when the pH decreases and approaches the isoelectric point, it becomes cationic in some parts, making it easier for bacteria to adhere. Because block copolymer P6 is nonionic, its charge does not change even when the pH fluctuates. In addition, the following can be inferred from the results in Table 4. When the salt concentration of polymer cP1 (a zwitterionic polymer) increases, free water near the polymer is released, making it hydrophobic, making it easier for bacteria to adhere. Because block copolymer P6 is nonionic, water release near the polymer is less likely to occur when the salt concentration increases.

Claims

1. A microbial adhesion-inhibiting resin comprising a block copolymer composed of a polymer (A) of a monomer containing a monomer (a) represented by the following general formula (1) and a polymer (B) of a monomer containing one or more monomers selected from the group consisting of monomers (b) represented by the following general formulas (2) to (7): A microbial adhesion inhibiting resin, characterized in that it is a resin for inhibiting microbial adhesion. 【Chemistry 1】 【Chemistry 2】 【Chemistry 3】 【Chemistry 4】 【Chemistry 5】 【Chemistry 6】 【Chemistry 7】 (In formulas (1) to (7), R ０ is an alkyl group having 1 to 3 carbon atoms; R １ is a hydrogen atom or a methyl group, R ２ , R ７ each independently represents an alkylene group having 2 to 3 carbon atoms; R ３ , R ４ , R ５ , R ６ each independently represents a hydrogen atom or an alkyl group having 1 to 2 carbon atoms; ２ － , -SO ３ － , -OSO ３ － , -OSO ２ － , -OP(=O)(OR ８ ) O － , -OP(=O)(R ８ ) O － , -P(=O)(OR ８ ) O － , -P(=O)(R ８ ) O － R is a monovalent anion selected from ８ is an alkyl group having 1 to 3 carbon atoms, and n is an integer from 1 to 9.

2. 2. The microbial adhesion-inhibiting resin according to claim 1, wherein in the block copolymer, the molar ratio (A:B) of the polymer (A) to the polymer (B) is 1:50 to 50:

1.

3. 3. The microbial adhesion-inhibiting resin according to claim 1, wherein the block copolymer is a triblock copolymer, a diblock copolymer, or a multi-branched block copolymer.

4. The microbial adhesion inhibitory resin according to claim 1 or 2, wherein in the block copolymer, the degree of polymerization of the polymer (A) is 30 to 3,000, and the degree of polymerization of the polymer (B) is 20 to 20,000.

5. 3. The microbial adhesion-inhibiting resin according to claim 1, wherein in the block copolymer, a copolymerization ratio of the monomer (b) / the monomer (a) is 99 / 1 to 10 / 90 by molar ratio.

6. 3. An antibacterial and antiviral processed product coated with the microbial adhesion inhibiting resin according to claim 1 or 2.

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