Anti-biofilm agent, Anti-biofilm resin composition, and Anti-biofilm coating material

Abstract

The present invention provides an anti-biofilm agent, an anti-biofilm resin composition, and an anti-biofilm coating material, each having an excellent anti-biofilm effect of suppressing the formation of a biofilm. An anti-biofilm agent, an anti-biofilm resin composition, and an anti-biofilm coating material according to the present invention are characterized by containing: an acidic compound having a solubility in water at 25°C of 0.5 g / 100 mL or less and a pKa1 value at 25°C of 4.3 or less, and having at least one H-type acidic functional group selected from the group consisting of a carboxy group, a sulfo group, and a phosphonic acid group; and a surfactant having an HLB value of 16-20.

Description

Anti-biofilm agent, anti-biofilm resin composition, and anti-biofilm paint

[0001] The present invention relates to an anti-biofilm agent, an anti-biofilm resin composition, and an anti-biofilm paint.

[0002] Biofilms are membranes that surround microorganisms and are formed when microorganisms attached to a substance secrete extracellular polysaccharides (EPS). EPS acts as a barrier to protect the microorganisms, acts as a transport route for the microorganisms to take in nutrients, and protects the microorganisms inside the biofilm from environmental changes and chemical substances.

[0003] Biofilms form not only in natural environments such as ponds and rivers, but also inside plant pipes, causing problems such as the introduction of foreign matter into products when the biofilms peel off. Furthermore, when biofilms form on wet components used in bathrooms, kitchens, and other areas, they can cause slime and foul odors, resulting in hygiene problems. Furthermore, when biofilms form on the inner surfaces of aquariums, they can adversely affect the organisms in the aquarium. Therefore, there is a need to inhibit biofilm formation.

[0004] Patent Document 1 discloses a biofilm formation inhibitor containing palmitoleic acid as an active ingredient.

[0005] Patent Document 2 discloses a biofilm dispersant containing, as an active ingredient, a compound represented by a specific structural formula or a salt thereof.

[0006] Patent Document 3 discloses a method for obtaining antimicrobial, antiseptic and / or antifouling properties within or on the surface of an article and / or material for protection, in which a compound having a specific structural formula, or an adduct or salt thereof, is applied to the article and / or material.

[0007] Japanese Patent Laid-Open No. 10-101502 Japanese Patent Laid-Open No. 2020-117451 Special Publication No. 2013-503122

[0008] However, the biofilm formation inhibitors disclosed in Patent Documents 1 to 3 and the like are insufficient in their inhibitory effect on biofilm formation, and there is a demand for agents that have excellent anti-biofilm effects.

[0009] The present invention provides an anti-biofilm agent, an anti-biofilm resin composition, and an anti-biofilm paint that have an excellent anti-biofilm effect of suppressing biofilm formation.

[0010] The anti-biofilm agent of the present invention is characterized by containing an acidic compound having a solubility in water at 25°C of 0.5 g / 100 mL or less, a pKa1 at 25°C of 4.3 or less, and having at least one H-type acidic functional group selected from the group consisting of a carboxy group, a sulfo group, and a phosphonic acid group, and a surfactant having an HLB value of 16 to 20.

[0011] The anti-biofilm resin composition of the present invention is characterized by comprising the above-mentioned acidic compound, the above-mentioned surfactant, and a synthetic resin.

[0012] The anti-biofilm paint of the present invention is characterized by comprising the above-mentioned acidic compound, the above-mentioned surfactant, and a paint.

[0013] The anti-biofilm agent, anti-biofilm resin composition, and anti-biofilm paint of the present invention (hereinafter collectively referred to as the "anti-biofilm agent group") contain an acidic compound having a predetermined solubility in water at 25°C and pKa1 and having a predetermined H-type acidic functional group, and a surfactant having a predetermined HLB value. Therefore, the acidic compound is stably present on the surface of the substrate and exhibits excellent interaction with microorganisms, inhibiting the adhesion of microorganisms to the surface of the substrate. Even if microorganisms do adhere to the surface of the substrate, the proliferation of microorganisms on the surface of the substrate is inhibited, and the formation of a biofilm on the surface of the substrate can be inhibited (anti-biofilm effect).

[0014] In the numerical ranges described in stages in this specification, the upper or lower limit of a certain numerical range can be arbitrarily combined with the upper or lower limit of another numerical range. In the numerical ranges described in this specification, the upper or lower limit of the numerical range may be replaced with a value shown in an example or a value that can be unambiguously derived from an example. In this specification, a numerical value connected with "to" means a numerical range that includes the numbers before and after "to" as the lower and upper limits.

[0015] The group of anti-biofilm agents of the present invention contains an acidic compound having a solubility in water at 25°C of 0.5 g / 100 mL or less, a pKa1 at 25°C of 4.3 or less, and having at least one H-type acidic functional group selected from the group consisting of a carboxy group, a sulfo group, and a phosphonic acid group, and a surfactant having an HLB value of 16 to 20.

[0016] To achieve an anti-biofilm effect, not only antibacterial activity but also other performances are required, such as inhibiting bacterial adhesion to the substrate surface, inhibiting EPS secretion even when bacteria adhere, and ensuring that the active ingredient does not dissolve in water and remains stable on the substrate surface. Therefore, the antibiofilm effect of conventional antibacterial agents does not necessarily correlate with the antibiofilm effect of antibiofilm agents, and antibiofilm agents do not necessarily exhibit antibiofilm effects. On the other hand, the antibiofilm agents of the present invention, when configured as described above, exhibit the above performance and provide excellent antibiofilm effects.

[0017] [Acidic Compound] The anti-biofilm agent group contains, as an active ingredient, an acidic compound having a solubility in water at 25°C of 0.5 g / 100 mL or less, a pKa1 at 25°C of 4.3 or less, and having at least one H-type acidic functional group selected from the group consisting of a carboxyl group (-COOH), a sulfo group (-SO3H), and a phosphonic acid group [-P(=O)(OH)2].

[0018] The group of anti-biofilm agents contains an acidic compound having a pKa1 of 4.3 or less at 25°C and a specific H-type acidic functional group, and the H-type acidic functional group of the acidic compound is hydrophilic and exhibits excellent interaction with a surfactant having an HLB value limited to 16 to 20. Thus, the H-type acidic functional group of the acidic compound is easily exposed on the surface of the substrate together with the surfactant, exhibiting excellent interaction with microorganisms and inhibiting adhesion of microorganisms to the substrate, and even if the microorganisms do adhere to the substrate, inhibiting their proliferation and effectively inhibiting the formation of a biofilm on the surface of the substrate.

[0019] Furthermore, since the solubility of the acidic compound in water at 25°C is 0.5 g / 100 mL or less, the acidic compound has excellent resistance to water that comes into contact with the substrate, and the acidic compound remains stable on the substrate surface even in an environment where microorganisms are likely to grow. Furthermore, the portion of the acidic compound other than the H-type acidic functional group is positioned on the substrate side, with the H-type acidic functional group facing outward, thereby improving interaction with microorganisms. Therefore, the excellent interaction between the acidic compound and microorganisms can effectively inhibit the adhesion and growth of microorganisms, and effectively inhibit the formation of a biofilm on the substrate surface.

[0020] The H-type acidic functional group of the acidic compound includes at least one selected from the group consisting of a carboxy group (—COOH), a sulfo group (—SOH), and a phosphonic acid group [—P(═O)(OH)], with a carboxy group and a sulfo group being preferred, and a carboxy group being more preferred.

[0021] The number of H-type acidic functional groups in the acidic compound may be one or more, but preferably more, and more preferably 2 or 3. When the acidic compound has multiple H-type acidic functional groups, the acidic compound more effectively interacts with the surfactant, and more H-type acidic functional groups are arranged facing outward, resulting in the anti-biofilm agent having a more excellent anti-biofilm effect.

[0022] The acidic compound has a solubility in water at 25°C of 0.5 g / 100 mL or less, preferably 0.4 g / 100 mL or less, more preferably 0.3 g / 100 mL or less, more preferably 0.2 g / 100 mL or less, more preferably 0.15 g / 100 mL or less, and more preferably 0.1 g / 100 mL or less.

[0023] The solubility (g / 100 mL) of an acidic compound in water at 25° C. refers to the mass (g) of the acidic compound that can be dissolved in 100 mL of water, or the mass (g) of the acidic compound dissolved in 100 mL of water in a saturated aqueous solution at 25° C. Specifically, the solubility of an acidic compound in water at 25° C. refers to a value measured at 25° C. in accordance with OECD Chemicals Testing Guideline No. 105 (Water Solubility).

[0024] The acidic compound has a pKa1 of 4.3 or less, preferably 4.2 or less, more preferably 4.1 or less, more preferably 4.0 or less, and even more preferably 3.9 or less at 25° C. When the pKa1 of the acidic compound at 25° C. is 4.3 or less, the anti-biofilm agents exhibit a more excellent anti-biofilm effect.

[0025] Here, in the present invention, the electrolyte HA is A － and H ＋ When an acid dissociates into an acid and an acid salt to obtain the ionization equilibrium equation (1), the acid dissociation constant Ka is defined by equation (2), and pKa is defined as the common logarithm (3) of the reciprocal of the acid dissociation constant Ka.

[0026] When the acidic compound is a polyvalent acid, the polyvalent acid undergoes ionization in multiple stages, and pKa1 refers to the pKa calculated based on the ionization constant of the first stage.

[0027]

[0028] The pKa1 of an acidic compound at 25° C. refers to a value measured by titration. Specifically, the pKa1 can be determined by titrating an organic acid and sodium hydroxide at 25° C. and measuring the pH at 25° C. at the half-equivalent point (the point at which half the amount required for complete neutralization has been added dropwise).

[0029] The acidic compound is not particularly limited as long as it has the above-mentioned solubility in water at 25°C, pKa1 at 25°C, and a specific H-type acidic functional group. Examples of the acidic compound include benzilic acid, methylenedisalicylic acid, isophthalic acid, salicylic acid, 2,6-naphthalenedicarboxylic acid, 2,3-naphthalenedicarboxylic acid, cis-Δ4-tetrahydrophthalic acid, triglycolaminic acid, ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid, ethylenediaminedisuccinic acid trihydrate (e.g., (S,S)-ethylenediaminedisuccinic acid trihydrate), o-toleic acid, m-toluic acid, and p-toleic acid. The acidic compounds may be used alone or in combination of two or more.

[0030] The acidic compound preferably has an aromatic ring skeleton. Because the acidic compound has an aromatic ring skeleton, it has excellent resistance to water that comes into contact with the substrate, and the acidic compound remains stable on the substrate surface even in an environment where microorganisms are likely to grow. Furthermore, the portions of the acidic compound other than the H-type acidic functional groups are positioned on the substrate side, with the H-type acidic functional groups facing outward, thereby improving interaction with microorganisms. Therefore, the anti-biofilm agent group exhibits a superior anti-biofilm effect.

[0031] The aromatic ring skeleton may be a monocyclic aromatic ring or may be a condensed monocyclic aromatic ring (condensed aromatic ring). The aromatic ring is not particularly limited, and examples thereof include a benzene ring, a naphthalene ring, an anthracene ring, biphenyl, and phenoxyphenyl. A benzene ring and a naphthalene ring are preferred, and a benzene ring is more preferred. The aromatic ring has one or more hydrogen atoms abstracted from either the aromatic ring or the condensed aromatic ring, and is bonded to other atoms by a covalent bond.

[0032] The acidic compound preferably has an H-type acidic functional group (at least one selected from the group consisting of a carboxy group (-COOH), a sulfo group (-SO3H), and a phosphonic acid group [-P(=O)(OH)2]) directly bonded to the aromatic ring skeleton, more preferably a carboxy group or a sulfo group directly bonded to the aromatic ring skeleton, and even more preferably a carboxy group directly bonded to the aromatic ring skeleton. When the acidic compound has an H-type acidic functional group directly bonded to the aromatic ring skeleton, the portion of the acidic compound other than the H-type acidic functional group faces the substrate, and the H-type acidic functional group is more stably arranged facing outward, improving interaction with microorganisms. Therefore, the anti-biofilm agents exhibit superior anti-biofilm effects.

[0033] The molecular weight of the acidic compound is preferably 1000 or less, more preferably 900 or less, more preferably 800 or less, more preferably 700 or less, more preferably 600 or less, more preferably 500 or less, more preferably 400 or less, and more preferably 300 or less. The acidic compound is preferably not an oligomer or a polymer. When the molecular weight of the acidic compound is 1000 or less, the degree of freedom in the orientation of the H-type acidic functional group in the acidic compound is improved, and the interaction with the surfactant is improved, so that the anti-biofilm agent group exhibits a superior anti-biofilm effect.

[0034] The content of H-type acidic functional groups in the acidic compound is preferably 4.0 mmol / g or more, preferably 4.5 mmol / g or more, more preferably 5.0 mmol / g or more, more preferably 5.5 mmol / g or more, and more preferably 6.0 mmol / g or more. When the content of H-type acidic functional groups in the acidic compound is 4.0 mmol / g or more, the interaction between the H-type acidic functional groups in the acidic compound and the surfactant is improved, and the anti-biofilm agent group exhibits a more excellent anti-biofilm effect. The content of H-type acidic functional groups in the acidic compound is preferably 18 mmol / g or less. When the content of H-type acidic functional groups in the acidic compound is 18 mmol / g or less, the hydrophilicity of the acidic compound is reduced, thereby suppressing elution into water, and an excellent anti-biofilm effect is exhibited over a long period of time.

[0035] The content of H-type acidic functional groups in the acidic compound refers to a value measured by titration. Specifically, approximately 1 g (X g) of dried acidic compound is precisely weighed, 200 mL of purified water is added to the acidic compound, and then titration is carried out at 25°C using a 0.1 mol / L aqueous sodium hydroxide solution. The amount of aqueous sodium hydroxide solution consumed (Y mL) up to the half-equivalent point (the point at which half the amount required for complete neutralization has been added dropwise) is determined, and the content (mmol / g) of H-type acidic functional groups in the acidic compound is calculated using the following formula: Content (mmol / g) of H-type acidic functional groups = 0.1 × X / Y

[0036] The pH of a 0.5% by mass aqueous solution of the acidic compound at 25°C is preferably 4.2 or less, and more preferably 4.0 or less, since this makes it easier to maintain the acidity of the H-type acidic functional group of the acidic compound and improves the anti-biofilm effect of the anti-biofilm agents.

[0037] The pH of a 0.5% by mass aqueous solution of an acidic compound refers to the pH value at 25°C of an aqueous solution obtained by adding 0.5 g of the acidic compound to 99.5 g of purified water and uniformly mixing the mixture. When the concentration of the saturated aqueous solution of the acidic compound at 25°C is less than 0.5% by mass, the pH is the pH at 25°C of a suspension containing 0.5 parts by mass of the acidic compound and 99.5 parts by mass of water, in which the acidic compound has dissolved in water to its solubility and is saturated.

[0038] The acidic compound is preferably particulate. When the acidic compound is particulate, the D50 particle size of the acidic compound is preferably 0.5 μm or more, more preferably 10 μm or more, more preferably 50 μm or more, more preferably 70 μm or more, more preferably 90 μm or more, and more preferably 100 μm or more. The D50 particle size of the acidic compound is preferably 300 μm or less, more preferably 280 μm or less, more preferably 250 μm or less, more preferably 220 μm or less, more preferably 200 μm or less, more preferably 180 μm or less, and more preferably 160 μm or less. By setting the D50 particle size of the acidic compound within the above-mentioned range, the amount of H-type acidic functional groups present on the surface of the particulate acidic compound can be more appropriately adjusted, and an even more excellent anti-biofilm effect can be imparted to the substrate.

[0039] The D50 particle size of each acidic compound refers to the particle size (50% cumulative particle size) at which the cumulative frequency (cumulative from particles with small particle sizes) in the volume-based particle size distribution determined by laser scattering method is 50%.

[0040] [Surfactant] The anti-biofilm agent group contains a surfactant with an HLB value of 16 to 20. Surfactants with an HLB value within a predetermined range have excellent affinity with the H-type acidic functional groups of the acidic compounds, and have the effect of directing the H-type acidic functional groups outward, improving the interaction between the H-type acidic functional groups and microorganisms, thereby imparting an excellent anti-biofilm effect to the substrate.

[0041] A surfactant is a compound having a hydrophilic group and a lipophilic group in one molecule. The HLB of a surfactant is the hydrophilic-lipophilic balance, and is a value that changes depending on the balance between the hydrophilic group and the lipophilic group in the molecule. A larger HLB value indicates higher hydrophilicity. In the present invention, the HLB value of a surfactant is a value calculated by the calculation formula proposed by Griffin [Griffin method: 20 × (sum of formula weights of hydrophilic moieties (e.g., alkyl ether moieties) in the surfactant / molecular weight of the surfactant)]. When the surfactant contains two or more surfactants, the "HLB value of the surfactant" refers to a weighted average of the HLB values ​​of the individual surfactants based on the mass content of the surfactants.

[0042] The surfactant is not particularly limited as long as it has an HLB value of 16 to 20, and may be any of anionic surfactants, cationic surfactants, nonionic surfactants, and amphoteric surfactants. However, nonionic surfactants are preferred because they have excellent interaction with the H-type acidic functional groups of acidic compounds and have excellent anti-biofilm effects among the anti-biofilm agents.

[0043] Examples of surfactants include potassium oleate (HLB value: 20), sodium oleate (HLB value: 18), polyoxyalkylene fatty acid esters (e.g., polyethylene glycol monostearate, polyethylene glycol distearate, etc.), alkyl glycosides, sucrose fatty acid esters, glycerin fatty acid esters, sorbitan fatty acid esters, fatty acid alkanolamides, polyoxyethylene fatty acid alkanolamides, polyoxyethylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene polyoxypropylene glycol, and polyoxyalkylene alkenyl ethers, with polyoxyalkylene fatty acid esters being preferred and polyoxyethylene fatty acid esters being more preferred.

[0044] With respect to the fatty acid ester component of the polyoxyalkylene fatty acid ester, the total number of carbon atoms in the fatty acid ester is preferably 10 to 24, more preferably 12 to 22, more preferably 14 to 20, and even more preferably 16 to 20. When the total number of carbon atoms in the fatty acid ester is within the above range, the interaction with the H-type acidic functional group of the acidic compound is excellent, and an excellent anti-biofilm effect can be imparted to the substrate.

[0045] Examples of higher fatty acids having a total carbon number of 10 to 24 include saturated higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, arachic acid, and behenic acid, and unsaturated higher fatty acids such as palmitoleic acid, oleic acid, elaidic acid, linoleic acid, linolenic acid, erucic acid, and ricinoleic acid, with saturated higher fatty acids being preferred, and palmitic acid and stearic acid being more preferred.

[0046] The polyoxyalkylene structure means a repeating unit represented by the following general formula: -(R 1 -O)n- (wherein, R 1 represents an alkylene group having 1 to 14 carbon atoms, and n is the number of repeating units and is a natural number of 2 or more.

[0047] An alkylene group is a divalent atomic group formed by removing two hydrogen atoms bonded to two different carbon atoms in an aliphatic saturated hydrocarbon, and includes both linear and branched atomic groups. Note that branched includes a case where one carbon (methyl group) is bonded as a side chain.

[0048] Examples of the alkylene group include an ethylene group, a propylene group [-CH(CH3)-CH2-], a trimethylene group [-CH2-CH2-CH2-], a butylene group, an amylene group [-(CH2)5-], and a hexylene group.

[0049] The degree of polymerization of the polyoxyalkylene portion of the polyoxyalkylene fatty acid ester is preferably 20 or more, more preferably 50 or more, and more preferably 100 or more. The degree of polymerization of the polyoxyalkylene portion of the polyoxyalkylene fatty acid ester is preferably 400 or less, more preferably 300 or less, and more preferably 200 or less. When the degree of polymerization of the polyoxyalkylene portion of the polyoxyalkylene fatty acid ester is within the above range, it exhibits excellent interaction with the H-type acidic functional group of the acidic compound, and can impart excellent anti-biofilm effects to the anti-biofilm agents.

[0050] The melting point of the surfactant is preferably 30° C. or higher, more preferably 35° C. or higher, more preferably 40° C. or higher, more preferably 45° C. or higher, and more preferably 50° C. or higher. The melting point of the surfactant is preferably 80° C. or lower, more preferably 75° C. or lower, more preferably 70° C. or lower, and more preferably 65° C. or lower. When the melting point of the surfactant is within the above range, it exhibits excellent interaction with the H-type acidic functional group of the acidic compound, and can impart excellent anti-biofilm effect to the substrate.

[0051] The melting point of the surfactant refers to a temperature measured by differential scanning calorimetry in accordance with JIS K7121:1987.

[0052] The content of the surfactant is preferably 5 parts by mass or more, more preferably 10 parts by mass or more, more preferably 15 parts by mass or more, and more preferably 20 parts by mass or more, relative to 100 parts by mass of the acidic compound. The content of the surfactant is preferably 50 parts by mass or less, more preferably 45 parts by mass or less, more preferably 40 parts by mass or less, more preferably 35 parts by mass or less, and more preferably 30 parts by mass or less, relative to 100 parts by mass of the acidic compound. When the content of the surfactant is 5 parts by mass or more, the interaction with the H-type acidic functional group of the acidic compound is excellent, and an excellent anti-biofilm effect can be imparted to the substrate. When the content of the surfactant is 50 parts by mass or less, the elution of the acidic compound into water is reduced, so the anti-biofilm effect can be maintained for a long period of time.

[0053] [Anti-biofilm Agent] The anti-biofilm agent can be produced by mixing a predetermined acidic compound and a surfactant in a known manner.

[0054] The anti-biofilm agent has an anti-biofilm effect against various microorganisms due to the action of an acidic compound and a surfactant.

[0055] The microorganism is not particularly limited as long as it is a microorganism that forms a biofilm, and may be a prokaryote such as a bacterium, or a eukaryote such as a yeast or a mold. The bacterium may be either a gram-positive bacterium or a gram-negative bacterium.

[0056] Examples of Gram-positive bacteria include bacteria of the genus Bacillus (e.g., Bacillus coagulans, Bacillus anthracis, Bacillus atrophaeus, Bacillus cereus, Bacillus megaterium, Bacillus pumilus, Bacillus subtilis, etc.), bacteria of the genus Clostridium (e.g., Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium sporogenes, Clostridium tetani, etc.), bacteria of the genus Enterococcus (e.g., Enterococcus faecalis, Enterococcus faecium, etc.), and bacteria of the genus Lactobacillus (e.g., Lactobacillus brevis, Lactobacillus fructivorans, Lactobacillus plantarum, etc.), Mycobacterium bacteria (e.g., Mycobacterium bovis, Mycobacterium leprae, Mycobacterium terrae, Mycobacterium tuberculosis, etc.), Propionibacterium bacteria (e.g., Propionibacterium acnes, etc.), Staphylococcus bacteria (e.g., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus saprophyticus, etc.), Streptococcus bacteria (e.g., Streptococcus mitis, Streptococcus Streptococcus mutansoralis, Streptococcus pneumoniae, Streptococcus pyogenes, etc.

[0057] Examples of Gram-negative bacteria include Bordetella bacteria (e.g., Bordetella pertussis), Campylobacter bacteria (e.g., Campylobacter jejuni), Enterobacter bacteria (e.g., Enterobacter cloacae), Escherichia bacteria (e.g., Escherichia coli), Fusobacterium bacteria (e.g., Fusobacterium nucleatum), Helicobacter bacteria (e.g., Helicobacter pylori), Klebsiella bacteria (e.g., Klebsiella pneumoniae), and Neisseria bacteria (e.g., Neisseria gonorrhoeae). meningitidis, etc.), Pseudomonas bacteria (e.g., Pseudomonas aeruginosa, Pseudomonas putida, etc.), Salmonella bacteria (e.g., Salmonella enterica serovar Typhi, Salmonella enterica serovar Paratyphi A, Salmonella enterica serovar Typhimurium, Salmonella enterica serovar Enteritidis, etc.), Serratia bacteria (e.g., Serratia marcescens, etc.), Vibrio bacteria (e.g., Vibrio cholerae, Vibrio parahaemolyticus, etc.), etc.

[0058] The anti-biofilm agent may be used by adhering (supporting) it to the surface of base particles. By adhering the anti-biofilm agent to the surface of the base particles, the anti-biofilm agent can be more uniformly dispersed in the substrate. Furthermore, the surface area of ​​the anti-biofilm agent can be increased. Therefore, sufficient contact between the anti-biofilm agent and microorganisms can be ensured, allowing the anti-biofilm effect of the anti-biofilm agent to be fully exerted.

[0059] The base particles to which the anti-biofilm agent adheres are not particularly limited as long as they do not inhibit the anti-biofilm effect of the anti-biofilm agent. The base particles may be either resin particles or inorganic particles. The base particles may be used alone or in combination of two or more types.

[0060] Examples of synthetic resins constituting the resin particles include styrene-based resins, acrylic-based resins, urethane-based resins, vinyl chloride-based resins, ABS resins, and synthetic rubbers such as styrene-butadiene rubber (SBR) and nitrile-butadiene rubber (NBR), with styrene-based resins and acrylic resins being preferred. In the present invention, "synthetic resin" refers to a compound having a molecular main chain mainly composed of covalent bonds and a molecular weight of 10,000 or more.

[0061] The styrene-based resin is not particularly limited, and examples thereof include homopolymers or copolymers containing, as monomer units, styrene-based monomers such as styrene, methylstyrene, ethylstyrene, i-propylstyrene, dimethylstyrene, chlorostyrene, and bromostyrene, and copolymers containing, as monomer units, a styrene-based monomer and one or more vinyl monomers copolymerizable with the styrene-based monomer.

[0062] Examples of vinyl monomers copolymerizable with styrene-based monomers include acrylic monomers such as acrylonitrile, methacrylonitrile, acrylic acid, methacrylic acid, acrylic acid esters (methyl acrylate, ethyl acrylate, butyl acrylate, etc.), methacrylic acid esters (methyl methacrylate, ethyl methacrylate, butyl methacrylate, etc.), maleic anhydride, and acrylamide.

[0063] The acrylic resin is not particularly limited, and examples thereof include homopolymers or copolymers containing, as monomer units, acrylic monomers such as methyl (meth)acrylate, ethyl (meth)acrylate, butyl (meth)acrylate, and pentyl (meth)acrylate, and copolymers containing, as monomer units, an acrylic monomer and one or more vinyl monomers copolymerizable with the acrylic monomer. Note that (meth)acrylate means acrylate or methacrylate.

[0064] Examples of vinyl monomers copolymerizable with acrylic monomers include acrylonitrile, methacrylonitrile, maleic anhydride, and acrylamide.

[0065] The inorganic material constituting the inorganic particles is not particularly limited, and examples thereof include zeolite, hydrotalcite, calcium carbonate, calcium citrate, magnesium carbonate, and magnesium hydroxide.

[0066] The synthetic resin constituting the resin particles preferably contains an aromatic ring skeleton, which attracts the hydrophobic moiety of the acidic compound attached to the surface of the resin particles and orients the H-type acidic functional groups of the acidic compound outward, thereby enabling the anti-biofilm agent to more effectively exert its anti-biofilm effect.

[0067] The aromatic ring skeleton may be a monocyclic aromatic ring or may be a condensed aromatic ring formed by condensing monocyclic aromatic rings. The aromatic ring is not particularly limited, and examples thereof include a benzene ring, a naphthalene ring, an anthracene ring, biphenyl, and phenoxyphenyl. The aromatic ring is formed by removing (abtracting) one or more hydrogen atoms from either the aromatic ring or the condensed aromatic ring, and is bonded to other atoms by a covalent bond.

[0068] The amount of the anti-biofilm agent attached to the base particles is preferably 1 part by mass or more, more preferably 5 parts by mass or more, more preferably 7 parts by mass or more, and even more preferably 10 parts by mass or more, per 100 parts by mass of the base particles. When the amount of the anti-biofilm agent attached is 1 part by mass or more, the anti-biofilm agent can be uniformly attached to the surface of the base particles, and the anti-biofilm effect of the anti-biofilm agent can be more effectively exerted.

[0069] The amount of the anti-biofilm agent attached to the base particles is preferably 1000 parts by mass or less, more preferably 800 parts by mass or less, more preferably 600 parts by mass or less, and even more preferably 400 parts by mass or less, per 100 parts by mass of the base particles. When the amount of the anti-biofilm agent attached is 1000 parts by mass or less, the anti-biofilm agents do not bond to each other, and the anti-biofilm agent is efficiently arranged on the surface of the base particles, improving the anti-biofilm effect.

[0070] The method for attaching the anti-biofilm agent to the surface of the base particle is not particularly limited, and may be, for example, by the adhesive strength of the anti-biofilm agent, or by using a binder resin to adhere the anti-biofilm agent to the surface of the base particle. However, since this allows the anti-biofilm effect of the anti-biofilm agent to be effectively exerted, it is preferable that the anti-biofilm agent be attached to the surface of the base particle by the adhesive strength of the anti-biofilm agent itself.

[0071] The anti-biofilm agent is used by being contained in a substrate to which an anti-biofilm effect is to be imparted, and the substrate containing the anti-biofilm agent exhibits an anti-biofilm effect as an anti-biofilm product.

[0072] The substrate for containing the anti-biofilm agent is not particularly limited as long as it is capable of containing the anti-biofilm agent, and examples include water supply and drainage pipes, kitchen utensils and kitchen components, washroom utensils and washroom components, bathroom utensils and bathroom components, toilet utensils and toilet components, cleaning supplies and components for cleaning equipment, cooking utensils and components for cooking equipment, water storage supplies and components for water storage equipment, humidifiers and components for humidifier equipment, air conditioning supplies and components for air conditioning equipment, water treatment supplies and components for water treatment equipment, agricultural supplies and components for agricultural equipment, fishing supplies and components for fishing equipment, components for manufacturing equipment, components for river and port facilities, components for water utilization equipment, and components for civil engineering facilities.

[0073] Methods for incorporating an anti-biofilm agent into the substrate include a method of mixing the anti-biofilm agent into a molded body that constitutes the substrate, and a method of applying a paint or the like containing the anti-biofilm agent to the surface of the substrate and coating it with a coating film containing the anti-biofilm agent.

[0074] [Anti-biofilm resin composition] The anti-biofilm resin composition contains the acidic compound, the surfactant, and a synthetic resin. The anti-biofilm resin composition can be obtained by mixing the acidic compound, the surfactant, and the synthetic resin in a known manner. The anti-biofilm resin composition may be prepared by mixing the anti-biofilm agent with the synthetic resin, or by separately mixing the acidic compound and the surfactant with the synthetic resin.

[0075] The anti-biofilm resin composition can be used by a general-purpose synthetic resin molding method to obtain an anti-biofilm product containing a molded body containing a synthetic resin and the acidic compound and surfactant contained in the molded body. Examples of general-purpose synthetic resin molding methods include extrusion molding, injection molding, and blow molding. The anti-biofilm resin composition containing a synthetic resin, the acidic compound, and the surfactant may be used as a synthetic resin molding masterbatch, and the synthetic resin molding masterbatch may be mixed with a synthetic resin as a raw material to produce an anti-biofilm product using a general-purpose synthetic resin molding method.

[0076] The synthetic resin constituting the molded body is not particularly limited, and examples thereof include thermoplastic resins (e.g., polyethylene, polypropylene, polyvinyl chloride, polystyrene, polyvinyl acetate, polyurethane, Teflon (registered trademark), acrylonitrile butadiene styrene resin, acrylonitrile styrene resin, acrylic resin, polyvinyl alcohol, polyamide, polyacetal, polycarbonate, modified polyphenylene ether, polyester, polyethylene terephthalate, polybutylene terephthalate, cyclic polyolefin, polyphenylene sulfide, polytetrafluoroethylene, polysulfone, polyethersulfone, polyarylate, polyether ether ketone, thermoplastic polyimide, polyamide imide, etc.), thermosetting resins (e.g., phenolic resin, epoxy resin, melamine resin, urea resin, unsaturated polyester resin, alkyd resin, silicone resin, polyurethane, thermosetting polyimide, etc.). The synthetic resins may be used alone or in combination of two or more.

[0077] The total content of the acidic compound and the surfactant in the anti-biofilm resin composition (except when used as a synthetic resin molding masterbatch) is more preferably 0.1 parts by mass or more, more preferably 0.2 parts by mass or more, more preferably 1 part by mass or more, and more preferably 2 parts by mass or more, per 100 parts by mass of synthetic resin. The total content of the acidic compound and the surfactant in the anti-biofilm resin composition is more preferably 900 parts by mass or less, more preferably 800 parts by mass or less, more preferably 200 parts by mass or less, and more preferably 100 parts by mass or less, per 100 parts by mass of synthetic resin. When the total content of the acidic compound and the surfactant in the anti-biofilm resin composition is 0.1 parts by mass or more, the anti-biofilm effect of the anti-biofilm resin composition can be improved. When the total content of the acidic compound and the surfactant in the anti-biofilm resin composition is 900 parts by mass or less, the acidic compound is more likely to be uniformly dispersed without agglomeration without affecting the physical properties of the synthetic resin, thereby improving the anti-biofilm effect.

[0078] The anti-biofilm resin composition can be used as a masterbatch for synthetic resin molding. The synthetic resin used in the masterbatch for synthetic resin molding can be any of the synthetic resins exemplified as the synthetic resin constituting the molded body. Only one type of synthetic resin may be used, or two or more types may be used in combination.

[0079] The total content of the acidic compound and the surfactant in the synthetic resin molding masterbatch is preferably 10 parts by mass or more, more preferably 15 parts by mass or more, and more preferably 20 parts by mass or more, per 100 parts by mass of the synthetic resin. The total content of the acidic compound and the surfactant in the synthetic resin molding masterbatch is preferably 120 parts by mass or less, more preferably 110 parts by mass or less, more preferably 105 parts by mass or less, more preferably 80 parts by mass or less, more preferably 70 parts by mass or less, and more preferably 60 parts by mass or less, per 100 parts by mass of the synthetic resin.

[0080] The anti-biofilm resin composition, particularly the synthetic resin molding masterbatch, may contain an antioxidant. The antioxidant is not particularly limited, and examples thereof include phosphorus-based antioxidants, phenol-based antioxidants, and thioether-based antioxidants. When the anti-biofilm resin composition further contains an antioxidant, the heat resistance of the resulting anti-biofilm resin composition and anti-biofilm product is further improved, and an anti-biofilm product with excellent appearance can be obtained for a long period of time.

[0081] The content of the antioxidant in the anti-biofilm resin composition (except when used as a masterbatch for synthetic resin molding) is preferably 0.01 parts by mass or more, more preferably 0.02 parts by mass or more, more preferably 0.03 parts by mass or more, and more preferably 0.05 parts by mass or more, per 100 parts by mass of synthetic resin. The content of the antioxidant in the anti-biofilm resin composition (except when used as a masterbatch for synthetic resin molding) is preferably 0.5 parts by mass or less, more preferably 0.4 parts by mass or less, and more preferably 0.3 parts by mass or less, per 100 parts by mass of synthetic resin.

[0082] The content of the antioxidant in the synthetic resin molding masterbatch is preferably 0.3 parts by mass or more, more preferably 0.5 parts by mass or more, and even more preferably 0.8 parts by mass or more, per 100 parts by mass of the synthetic resin. The content of the antioxidant in the synthetic resin molding masterbatch is preferably 4 parts by mass or less, more preferably 3 parts by mass or less, and even more preferably 2 parts by mass or less, per 100 parts by mass of the synthetic resin.

[0083] The synthetic resin molding masterbatch is preferably in the form of resin pellets because of its excellent moldability. By melting and molding the resin pellets, an anti-biofilm product (synthetic resin molded product) with excellent anti-biofilm effects can be obtained.

[0084] The shape of the resin pellets is not particularly limited, and examples thereof include spherical, cylindrical, and prismatic shapes. From the viewpoint of pellet shape stability, a cylindrical shape is preferred. The maximum length dimension of the resin pellets is preferably 1 mm or more, more preferably 3 mm or more. The maximum length dimension of the resin pellets is preferably 10 mm or less, more preferably 7 mm or less.

[0085] The synthetic resin molding masterbatch can be used by mixing with other resin materials. The other resin materials may be resin pellets. The synthetic resin molding masterbatch and the other resin materials are mixed to obtain a mixed resin material, and then the mixed resin material is molded to obtain an anti-biofilm product (synthetic resin molded article) with excellent anti-biofilm effects.

[0086] [Anti-biofilm paint] The anti-biofilm paint contains the acidic compound, the surfactant, and a paint. The anti-biofilm paint can be obtained by mixing the acidic compound, the surfactant, and the paint in a known manner. The anti-biofilm paint may be prepared by mixing the anti-biofilm agent into the paint, or by mixing the acidic compound and the surfactant separately into the paint. A coating film formed from the anti-biofilm paint exhibits excellent anti-biofilm effects.

[0087] As the paint, conventionally known paints are used. Paints usually contain a synthetic resin as a binder component. Both hydrophobic and hydrophilic paints can be used. Hydrophobic paints are not particularly limited, and examples thereof include oil-based paints (e.g., mixed paints, oil varnishes, etc.), cellulose paints, and synthetic resin paints. Paints also include photocurable paints that polymerize upon irradiation with radiation such as ultraviolet light to produce a binder component. Hydrophilic paints are not particularly limited, and examples thereof include water-based urethane paints, water-based silicone paints, water-based fluorine paints, and water-based inorganic paints.

[0088] The paint may contain additives such as pigments, plasticizers, curing agents, extenders, fillers, antioxidants, and thickeners, as long as the additives do not impair the paint's physical properties. Examples of methods for incorporating the acidic compound and surfactant into the paint include a method in which the acidic compound, surfactant, paint, and additives added as needed are supplied to a dispersing device and mixed uniformly. Examples of dispersing devices include a high-speed mill, a ball mill, and a sand mill.

[0089] The coating material may contain a solvent such as an aqueous solvent or an organic solvent to adjust the viscosity. The aqueous solvent is not particularly limited, and examples thereof include water, lower alcohols (e.g., alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propanol, and butanol), and mixtures of water and lower alcohols. The organic solvent is not particularly limited, and examples thereof include toluene, xylene, methyl ethyl ketone, acetone, ethyl acetate, benzene, and isopropyl alcohol. The solvents may be used alone or in combination.

[0090] The total content of the acidic compound and the surfactant in the anti-biofilm paint is preferably 0.1% by mass or more, more preferably 1% by mass or more, and more preferably 2% by mass or more. The total content of the acidic compound and the surfactant in the anti-biofilm paint is preferably 10% by mass or less, more preferably 7% by mass or less, and more preferably 5% by mass or less. When the total content of the acidic compound and the surfactant is 0.1% by mass or more, the coating film formed from the anti-biofilm paint exhibits excellent anti-biofilm effect. When the total content of the acidic compound and the surfactant is 10% by mass or less, the coatability of the anti-biofilm paint and the appearance of the resulting coating film are improved.

[0091] The present invention will be described in more detail below using examples, but the present invention is not limited thereto. Specific numerical values ​​of the blending ratios (content ratios), physical property values, parameters, etc. used in the following description can be replaced with the upper limit values ​​(numeric values ​​defined as "equal to or less than") or lower limit values ​​(numeric values ​​defined as "equal to or greater than") of the corresponding blending ratios (content ratios), physical property values, parameters, etc. described in the "Summary of the Invention."

[0092] The compounds used in the production of the anti-biofilm agents of the Examples and Comparative Examples are shown below. [Acidic compounds] Benzilic acid Methylenedisalicylic acid Isophthalic acid Salicylic acid 2,6-naphthalenedicarboxylic acid 2,3-naphthalenedicarboxylic acid cis-Δ4-tetrahydrophthalic acid Phthalic acid p-toluenesulfonic acid Sebacic acid Dodecanedioic acid

[0093] The table shows the solubility in water at 25°C, pKa1 at 25°C, molecular weight, content of H-type acidic functional groups, pH of a 0.5% by mass aqueous solution at 25°C, and D50 particle size for the above acidic compounds.

[0094] In the tables, "solubility in water at 25°C," "pKa1 at 25°C," "content of H-type acidic functional groups," and "pH of a 0.5% by mass aqueous solution at 25°C" are represented as "water solubility," "pKa1," "amount of H-type acidic functional groups," and "pH," respectively.

[0095] [Surfactants] Polyoxyethylene monostearate 1 (PEG 1 monostearate, degree of polymerization of polyoxyethylene moiety: 150, manufactured by Kao Corporation, trade name "Emanon 3199VB") Polyoxyethylene monostearate 2 (PEG 2 monostearate, degree of polymerization of polyoxyethylene moiety: 40, manufactured by Nikko Chemicals Co., Ltd., trade name "NIKKOLMYS-40V") Polyoxyethylene monostearate 3 (PEG 3 monostearate, degree of polymerization of polyoxyethylene moiety: 2, manufactured by Nippon Surfactant Industry Co., Ltd., trade name "NIKKOLMYS-2V") Polyoxyethylene monostearate 4 (PEG 4 monostearate, degree of polymerization of polyoxyethylene moiety: 12, manufactured by Kao Corporation, trade name "Emanon 1112") Polyoxyethylene distearate 1 (PEG 1 distearate, degree of polymerization of polyoxyethylene moiety: 250, Kao Corporation, trade name "Emanon 3299RV") Polyoxyethylene distearate 2 (PEG 2 distearate, degree of polymerization of polyoxyethylene moiety: 150, Nikko Chemicals Co., Ltd., trade name "NIKKOLCDS-6000P") Polyoxyethylene distearate 3 (PEG 3 distearate, degree of polymerization of polyoxyethylene moiety: 150, Kao Corporation, trade name "Emanon 3299VB") Glycol distearate (Toho Chemical Co., Ltd., trade name "Pegnol EDS(S)") Lauric acid diethanolamide (Kao Corporation, trade name "Aminone L-02") Propylene glycol monostearate (Riken Vitamin Co., Ltd., trade name "Rikemal PS100")・Glycol monostearate (manufactured by Nikko Chemicals Co., Ltd., trade name "NIKKOLMYS-1EXV") ・Polyoxyethylene lauryl ether (manufactured by Kao Corporation, trade name "Emulgen 104P") ・Polyoxyethylene monoethanolamide laurate (manufactured by Kawaken Fine Chemicals Co., Ltd., trade name "Amizet 2L-Y") ・Polyoxyethylene stearyl ether (manufactured by Kao Corporation, trade name "Emulgen 306P") ・Stearic acid diethanolamide (manufactured by Kawaken Fine Chemicals Co., Ltd., trade name "Amizol SDHE")

[0096] The HLB values ​​and melting points of the above surfactants are shown in the table.

[0097] (Examples 1 to 13 and Comparative Examples 1 to 17) Anti-biofilm agents were prepared by uniformly mixing the acidic compound and surfactant in the amounts shown in the "Content (parts by mass)" column in the table.

[0098] An anti-biofilm resin composition was prepared by melt-kneading 2 parts by mass of the anti-biofilm agent and 98 parts by mass of polypropylene (trade name "Novalock PP BC6C", manufactured by Japan Polypropylene Corporation) at 220°C for 10 minutes.

[0099] The obtained anti-biofilm resin composition was press-molded to obtain a sheet-shaped synthetic resin molded body having an average thickness of 1 mm as an anti-biofilm product.

[0100] The polypropylene alone was press-molded to obtain a sheet-like synthetic resin molded product having an average thickness of 1 mm as an unprocessed product.

[0101] The antibiofilm activity values ​​of the obtained antibiofilm product and the untreated product were measured in accordance with ISO 4768 as follows, and the results are shown in the table.

[0102] (Anti-biofilm activity value) A flat square anti-biofilm product with a side of 3 cm attached to a flat square glass plate with a side of 4 cm was placed in a sterilized container, and then 2 × 10 3A test bacterial solution of Staphylococcus epidermidis (Staphylococcus epidermidis ATCC35984) adjusted to CFU / mL was added and cultured at 35 ° C for 48 hours to form a biofilm. After culture, the anti-biofilm product attached to the glass plate was stained with a crystal violet solution, the surface was washed with purified water, and the stained biofilm was wiped off with a water-soluble nonwoven fabric. The resulting water-soluble nonwoven fabric was added to 5 mL of a 1% aqueous solution of sodium dodecyl sulfate and dissolved by shaking to obtain a solution. The absorbance (W treated) at 590 nm of the resulting solution was measured using a microplate reader. The same procedure as above was also performed on an unprocessed product with a flat square shape and 3 cm sides attached to a 4 cm square glass plate. The absorbance (W untreated) at 590 nm was measured, and the anti-biofilm activity value was calculated using the following formula. Antibiofilm activity value (%) = (1 - Wtreated / Wuntreated) x 100

[0103]

[0104]

[0105] The anti-biofilm agent, anti-biofilm resin composition and anti-biofilm paint of the present invention are stable on the surface of a substrate, exhibit excellent interaction with microorganisms, and inhibit the adhesion of microorganisms to the surface of the substrate. Even if microorganisms do adhere to the surface of the substrate, they can inhibit the proliferation of microorganisms on the surface of the substrate and inhibit the formation of a biofilm on the surface of the substrate.

[0106] (Cross-reference to related applications) This application claims priority based on Japanese Patent Application No. 2024-045937, filed on March 22, 2024, the disclosure of which is incorporated herein by reference in its entirety.

Claims

1. An anti-biofilm agent characterized by containing an acidic compound having a solubility in water at 25°C of 0.5 g / 100 mL or less, a pKa1 at 25°C of 4.3 or less, and having at least one H-type acidic functional group selected from the group consisting of a carboxy group, a sulfo group, and a phosphonic acid group, and a surfactant having an HLB value of 16 to 20.

2. The anti-biofilm agent according to claim 1, characterized in that the H-type acidic functional group of the acidic compound is a carboxy group or a sulfo group.

3. An anti-biofilm agent according to claim 1 or 2, characterized in that the molecular weight of the acidic compound is 1,000 or less.

4. An anti-biofilm agent according to claim 1 or 2, characterized in that the melting point of the surfactant is 30 to 230°C.

5. An anti-biofilm agent according to claim 1 or 2, characterized in that the amount of H-type acidic functional groups in the acidic compound is 4.0 mmol / g or more.

6. An anti-biofilm agent according to claim 1 or 2, characterized in that the pH of a 0.5% by mass aqueous solution of the acidic compound at 25°C is 4.2 or less.

7. An anti-biofilm agent according to claim 1 or 2, characterized in that it contains 5 to 100 parts by mass of the surfactant per 100 parts by mass of the acidic compound.

8. An anti-biofilm agent according to claim 1 or 2, characterized in that the D50 particle size of the acidic compound is 0.5 to 300 μm.

9. An anti-biofilm resin composition comprising: an acidic compound having a solubility in water at 25°C of 0.5 g / 100 mL or less, a pKa1 at 25°C of 4.3 or less, and having at least one H-type acidic functional group selected from the group consisting of a carboxy group, a sulfo group, and a phosphonic acid group; a surfactant having an HLB value of 16 to 20; and a synthetic resin.

10. An anti-biofilm resin composition as described in claim 9, characterized in that it contains a total of 0.1 to 900 parts by mass of the acidic compound and the surfactant per 100 parts by mass of the synthetic resin.

11. An anti-biofilm paint comprising: an acidic compound having a solubility in water at 25°C of 0.5 g / 100 mL or less, a pKa1 at 25°C of 4.3 or less, and having at least one H-type acidic functional group selected from the group consisting of a carboxy group, a sulfo group, and a phosphonic acid group; a surfactant having an HLB value of 16 to 20; and a paint.

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