WO2025197864A1 - Anti-biofilm agent, anti-biofilm resin composition, and anti-biofilm coating material - Google Patents

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

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

A biofilm is a membrane that surrounds microorganisms and is formed when microorganisms attached to a substance secrete extracellular polysaccharides (EPS). EPS acts as a barrier to protect the microorganisms and as a transport route for the microorganisms to take in nutrients, and also protects the microorganisms inside the biofilm from environmental changes and chemical substances.

Biofilms form not only in natural environments such as ponds and rivers, but also inside plant pipes, where they can peel off and cause problems with foreign matter being mixed into products. Furthermore, when biofilms form on wet components used in bathrooms, kitchens, etc., they can cause slime and foul odors, creating hygiene problems. Furthermore, when biofilms form on the inner surfaces of aquariums, they can have a negative impact on the organisms within the tank. Therefore, there is a need to suppress the formation of biofilms.

Patent Document 1 discloses a biofilm formation inhibitor that contains palmitoleic acid as an active ingredient.

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

Patent Document 3 discloses a method for obtaining antimicrobial, antiseptic and/or anti-microbial adhesion 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.

Japanese Patent Application Publication No. 10-101502 Japanese Patent Application Laid-Open No. 2020-117451 Special Publication No. 2013-503122

However, the biofilm formation inhibitors disclosed in Patent Documents 1 to 3 are insufficient in their ability to inhibit biofilm formation, and there is a demand for agents that have excellent anti-biofilm effects.

The present invention provides an anti-biofilm agent, an anti-biofilm resin composition, and an anti-biofilm paint that have excellent anti-biofilm effects that inhibit biofilm formation.

The anti-biofilm agent of the present invention comprises:
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.

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

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

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 with a predetermined solubility in water at 25°C and pKa1, and a predetermined H-type acidic functional group, and a surfactant with 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 is inhibited (anti-biofilm effect).

In the numerical ranges described in this specification in stages, the upper or lower limit of a numerical range in one stage can be arbitrarily combined with the upper or lower limit of a numerical range in another stage. In the numerical ranges described in this specification, the upper or lower limit of that 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, numbers connected with "~" mean a numerical range that includes the numbers before and after "~" as the upper and lower limits.

The anti-biofilm agents of the present invention contain an acidic compound that has 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 has 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 with an HLB value of 16 to 20.

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

[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 at least one H-type acidic functional group selected from the group consisting of a carboxy group (-COOH), a sulfo group (-SO3H), and a phosphonic acid group [-P(=O)(OH) ₂ ].

The anti-biofilm agent group contains acidic compounds with a pKa1 of 4.3 or less at 25°C and specific H-type acidic functional groups. The H-type acidic functional groups of the acidic compounds are hydrophilic and exhibit excellent interactions with surfactants with HLB values limited to 16 to 20. Therefore, the H-type acidic functional groups of the acidic compounds are easily exposed on the surface of the substrate along with the surfactant, exhibiting excellent interactions with microorganisms and inhibiting the adhesion of microorganisms to the substrate. Even if the microorganisms do adhere to the substrate, they inhibit the proliferation of microorganisms, effectively inhibiting the formation of a biofilm on the surface of the substrate.

Furthermore, because the solubility of the acidic compound in water at 25°C is 0.5 g/100 mL or less, 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 environments where microorganisms are likely to grow. Furthermore, by arranging the parts of the acidic compound other than the H-type acidic functional groups facing the substrate, with the H-type acidic functional groups facing outward, it is possible to improve interaction with microorganisms. Therefore, the excellent interaction between the acidic compound and microorganisms can effectively inhibit the attachment and growth of microorganisms, and effectively inhibit the formation of a biofilm on the substrate surface.

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 (-SO ₃ H), and a phosphonic acid group [-P(=O)(OH) ₂ ], with a carboxy group and a sulfo group being preferred, and a carboxy group being more preferred.

The number of H-type acidic functional groups in the acidic compound may be one or more, but it is preferable for the acidic compound to have more than one, and more preferably two or three. When the acidic compound has multiple H-type acidic functional groups, it interacts more effectively with surfactants, and by arranging more H-type acidic functional groups facing outward, the anti-biofilm agents exhibit superior anti-biofilm effects.

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.

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

The acidic compound has a pKa1 at 25°C 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. When the pKa1 at 25°C of the acidic compound is 4.3 or less, the anti-biofilm agent group exhibits superior anti-biofilm effects.

In the present invention, when the electrolyte HA is ionized into A ⁻ and H ⁺ 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.

If the acidic compound is a polyvalent acid, which undergoes ionization in multiple stages, pKa1 refers to the pKa calculated based on the ionization constant of the first stage.

The pKa1 of an acidic compound at 25°C is a value measured by titration. Specifically, 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 to complete neutralization has been added).

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 acidic compounds 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.

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 environments where microorganisms are likely to grow. Furthermore, by arranging the parts of the acidic compound other than the H-type acidic functional groups facing the substrate, with the H-type acidic functional groups facing outward, interaction with microorganisms can be improved. Therefore, the anti-biofilm agents exhibit superior anti-biofilm effects.

The aromatic ring skeleton may be a monocyclic aromatic ring, or may be a fused monocyclic aromatic ring (fused aromatic ring). The aromatic ring is not particularly limited, and examples 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 removed from either the aromatic ring or the fused aromatic ring, and is bonded to other atoms via a covalent bond.

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.

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. It is preferable that the acidic compound is not an oligomer or 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 groups in the acidic compound is improved, improving the interaction with surfactants, and the anti-biofilm agents exhibit superior anti-biofilm effects.

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 of 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 excellent anti-biofilm effects are exhibited over a long period of time.

The content of the H-type acidic functional group in the acidic compound is a value measured by titration. Specifically, about 1 g (X g) of the dried acidic compound is precisely weighed, 200 mL of purified water is added to the acidic compound, and the acidic compound is titrated with 0.1 mol/L aqueous sodium hydroxide at 25° C. The amount of aqueous sodium hydroxide 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 of the H-type acidic functional group (mmol/g) in the acidic compound is calculated using the following formula:
Content of H-type acidic functional groups (mmol/g) = 0.1 × X/Y

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, as this helps to maintain the acidity of the H-type acidic functional groups of the acidic compound and improves the anti-biofilm effect of the anti-biofilm agents.

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 mixing uniformly. If 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 reached a saturated state.

The acidic compound is preferably in particulate form. When the acidic compound is in particulate form, 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 range, the amount of H-type acidic functional groups present on the surface of the particulate acidic compound can be more appropriately adjusted, and even better anti-biofilm effects can be imparted to the substrate.

The D50 particle size of an 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 measured by laser scattering method is 50%.

[Surfactant]
The group of anti-biofilm agents contains surfactants 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.

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

The surfactant is not particularly limited as long as it has an HLB value of 16 to 20, and can 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 provide superior anti-biofilm effects among anti-biofilm agents.

Surfactants include, for example, 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, polyoxyalkylene alkenyl ethers, etc., with polyoxyalkylene fatty acid esters being preferred, and polyoxyethylene fatty acid esters being more preferred.

For 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, it exhibits excellent interaction with the H-type acidic functional groups of the acidic compound, and can impart excellent anti-biofilm effects to the substrate.

Examples of higher fatty acids having a total of 10 to 24 carbon atoms 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. Saturated higher fatty acids are preferred, with palmitic acid and stearic acid being more preferred.

The polyoxyalkylene structure means a repeating unit represented by the following general formula:
--(R ¹ --O)n--
(In the formula, ^R1 represents an alkylene group having 1 to 14 carbon atoms, and n represents the number of repeating units and is a natural number of 2 or more.)

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 straight-chain and branched atomic groups. Branched groups include those with one carbon atom (methyl group) bonded as a side chain.

Examples of the alkylene group include an ethylene group, a propylene group [--CH(CH ₃ )--CH ₂ --], a trimethylene group [--CH ₂ --CH ₂ --CH ₂ --], a butylene group, an amylene group [--(CH ₂ ) ₅ --], and a hexylene group.

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.

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 has excellent interaction with the H-type acidic functional groups of the acidic compound, and can impart excellent anti-biofilm effects to the substrate.

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

The surfactant content 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, per 100 parts by mass of the acidic compound. The surfactant content 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, per 100 parts by mass of the acidic compound. When the surfactant content is 5 parts by mass or more, excellent interaction with the H-type acidic functional groups of the acidic compound is achieved, imparting excellent anti-biofilm effects to the substrate. When the surfactant content is 50 parts by mass or less, elution of the acidic compound into water is reduced, allowing the anti-biofilm effect to be maintained for a long period of time.

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

Anti-biofilm agents have anti-biofilm effects against various microorganisms due to the action of acidic compounds and surfactants.

The microorganisms are not particularly limited as long as they are biofilm-forming microorganisms, and may be prokaryotes such as bacteria, or eukaryotes such as yeast or mold. The bacteria may be either gram-positive or gram-negative bacteria.

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 M perfringens, Clostridium sporogenes, Clostridium tetani, etc.), Enterococcus bacteria (e.g., Enterococcus faecalis, Enterococcus faecium, etc.), Lactobacillus bacteria (e.g., Lactobacillus brevis, Lactobacillus fructivorans, Lactobacillus plantarum, etc.), mycobacteria 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 Examples include Staphylococcus epidermidis (Staphylococcus epidermidis), Staphylococcus lugdunensis, Staphylococcus saprophyticus, etc.), and Streptococcus bacteria (for example, Streptococcus mitis, Streptococcus mutans, Streptococcus oralis, Streptococcus pneumoniae, Streptococcus pyogenes, etc.).

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 gonocol. Examples of bacteria that may be present include Neisseria gonorrhoeae, Neisseria 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), and Vibrio bacteria (e.g., Vibrio cholerae, Vibrio parahaemolyticus, etc.).

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 dispersed more uniformly within the substrate. Furthermore, the surface area of the anti-biofilm agent can be increased. This ensures sufficient contact between the anti-biofilm agent and microorganisms, allowing the anti-biofilm effect of the anti-biofilm agent to be fully exerted.

The base particles to which the anti-biofilm agent adheres to the surface 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.

Synthetic resins that make up the resin particles include, for example, 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 this invention, "synthetic resin" refers to a compound with a molecular main chain primarily composed of covalent bonds and a molecular weight of 10,000 or more.

Styrenic resins are not particularly limited, and examples 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.

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.

Acrylic resins are not particularly limited, and examples include homopolymers or copolymers containing acrylic monomers such as methyl (meth)acrylate, ethyl (meth)acrylate, butyl (meth)acrylate, and pentyl (meth)acrylate as monomer units, and copolymers containing acrylic monomers and one or more vinyl monomers copolymerizable with the acrylic monomer as monomer units. Note that (meth)acrylate refers to acrylate or methacrylate.

Vinyl monomers that can be copolymerized with acrylic monomers include acrylonitrile, methacrylonitrile, maleic anhydride, and acrylamide.

The inorganic material that makes up the inorganic particles is not particularly limited, and examples include zeolite, hydrotalcite, calcium carbonate, calcium citrate, magnesium carbonate, magnesium hydroxide, etc.

The synthetic resin that makes up the resin particles preferably contains an aromatic ring skeleton. The aromatic ring skeleton attracts the hydrophobic portion 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, allowing the anti-biofilm agent to more effectively exert its anti-biofilm effect.

The aromatic ring skeleton may be a monocyclic aromatic ring, or may be a combination of monocyclic aromatic rings fused together (a fused aromatic ring). The aromatic ring is not particularly limited, and examples include a benzene ring, a naphthalene ring, an anthracene ring, biphenyl, and phenoxyphenyl. An aromatic ring has one or more hydrogen atoms removed (pulled out) from either the aromatic ring or the fused aromatic ring, and is bonded to other atoms via a covalent bond.

The amount of 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 base particles. When the amount of 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, allowing the anti-biofilm effect of the anti-biofilm agent to be more effectively exerted.

The amount of anti-biofilm agent attached to the base particles is preferably 1,000 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 base particles. When the amount of anti-biofilm agent attached is 1,000 parts by mass or less, bonding between anti-biofilm agents does not occur, and the anti-biofilm agent is efficiently distributed on the surface of the base particles, improving the anti-biofilm effect.

The method for attaching the anti-biofilm agent to the surface of the base particles is not particularly limited; for example, the adhesive strength of the anti-biofilm agent may be used, or the anti-biofilm agent may be attached to the surface of the base particles using a binder resin. 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 particles by the adhesive strength of the anti-biofilm agent itself.

Anti-biofilm agents are used by being incorporated into a substrate to which an anti-biofilm effect is desired, and the substrate containing the anti-biofilm agent exhibits anti-biofilm effects as an anti-biofilm product.

The substrate for incorporating the anti-biofilm agent is not particularly limited as long as it is capable of incorporating the anti-biofilm agent, and examples include water supply and drainage pipes, kitchenware and kitchen components, washroom supplies and washroom components, bathroom supplies and bathroom components, toilet supplies and toilet components, cleaning supplies and components for cleaning equipment, cooking supplies and components for cooking equipment, water storage supplies and components for water storage facilities, humidifiers and components for humidifier equipment, air conditioning supplies and components for air conditioning equipment, water treatment supplies and components for water treatment facilities, 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.

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

[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.

The anti-biofilm resin composition can be used by a general-purpose synthetic resin molding method to obtain an anti-biofilm product that includes a molded body containing 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 synthetic resin, the acidic compound, and the surfactant can be used as a synthetic resin molding masterbatch, and the synthetic resin molding masterbatch can be mixed with the synthetic resin raw material to produce an anti-biofilm product using a general-purpose synthetic resin molding method.

The synthetic resin that constitutes the molded body is not particularly limited, and examples 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, polyetheretherketone, thermoplastic polyimide, polyamideimide, etc.), and thermosetting resins (e.g., phenolic resin, epoxy resin, melamine resin, urea resin, unsaturated polyester resin, alkyd resin, silicone resin, polyurethane, thermosetting polyimide, etc.). Synthetic resins may be used alone or in combination.

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 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 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.

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 that constitutes the molded body. Only one type of synthetic resin may be used, or two or more types may be used in combination.

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 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 synthetic resin.

Antioxidants may be added to the anti-biofilm resin composition, particularly the synthetic resin molding masterbatch. Antioxidants are not particularly limited, and examples include phosphorus-based antioxidants, phenol-based antioxidants, and thioether-based antioxidants. By further adding an antioxidant to the anti-biofilm resin composition, the heat resistance of the resulting anti-biofilm resin composition and anti-biofilm product is further improved, allowing for the production of anti-biofilm products that maintain excellent appearance over a long period of time.

The content of the antioxidant in the anti-biofilm resin composition (excluding 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 (excluding 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.

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 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 synthetic resin.

The synthetic resin molding masterbatch is preferably in the form of resin pellets, as they have 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.

The shape of the resin pellets is not particularly limited, and examples include spherical, cylindrical, and prismatic shapes. From the perspective 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.

The synthetic resin molding masterbatch can be used by mixing it with other resin materials. The other resin materials may be in the form of resin pellets. By mixing the synthetic resin molding masterbatch with the other resin materials to obtain a mixed resin material, and then molding the mixed resin material, an anti-biofilm product (synthetic resin molded product) with excellent anti-biofilm effects can be obtained.

[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.

The paint used can be any conventional paint known in the art. Paints typically contain a synthetic resin as a binder component. Both hydrophobic and hydrophilic paints can be used. Hydrophobic paints are not particularly limited, and examples 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 exposure to radiation such as ultraviolet light to produce a binder component. Hydrophilic paints are not particularly limited, and examples include water-based urethane paints, water-based silicone paints, water-based fluorine paints, and water-based inorganic paints.

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. One method for incorporating the acidic compound and surfactant into the paint is to supply the acidic compound, surfactant, paint, and optional additives to a dispersing device and mix them uniformly. Examples of dispersing devices include high-speed mills, ball mills, and sand mills.

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

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 even 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 even 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 effects. 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.

The present invention will be explained in more detail below using examples, but the present invention is not limited to these. Specific numerical values for blending ratios (content ratios), physical properties, parameters, etc. used in the following description can be replaced with the corresponding 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") for blending ratios (content ratios), physical properties, parameters, etc. described in the "Summary of the Invention" section.

The compounds used in the production of the anti-biofilm agents of the Examples and Comparative Examples are shown below.
[Acidic compound]
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

For the above acidic compounds, 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 are shown in the table.

In the table, "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 abbreviated as "water solubility," "pKa1," "amount of H-type acidic functional groups," and "pH," respectively.

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

The HLB values and melting points of the above surfactants are shown in the table.

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

2 parts by mass of the anti-biofilm agent and 98 parts by mass of polypropylene (manufactured by Japan Polypropylene Corporation, trade name "Novalock PP BC6C") were melt-kneaded and mixed at 220°C for 10 minutes to prepare an anti-biofilm resin composition.

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

The above polypropylene alone was press-molded to obtain a sheet-shaped synthetic resin molded product with an average thickness of 1 mm as an unprocessed product.

The antibiofilm activity values of the obtained antibiofilm product and the unprocessed product were measured in accordance with ISO 4768 as described below, and the results are shown in the table.

(Anti-biofilm activity value)
A 3 cm square anti-biofilm product attached to a 4 cm square glass plate was placed in a sterilized container, and a test bacterial solution of Staphylococcus epidermidis (ATCC 35984) adjusted to 2 x 10 ³ CFU/mL was added to the container 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 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 1% sodium dodecyl sulfate aqueous solution and dissolved by shaking to obtain a solution. The absorbance (Wtreated) of the resulting solution at 590 nm was measured using a microplate reader. The same procedure as above was also carried out on an unprocessed product with a flat square shape and 3 cm on each side attached to a 4 cm square glass plate with a flat square shape and 4 cm on each side.The absorbance at 590 nm (Wuntreated) was measured, and the antibiofilm activity value was calculated using the following formula.
Antibiofilm activity value (%) = (1 - Wtreated/Wuntreated) x 100

The anti-biofilm agent, anti-biofilm resin composition, and anti-biofilm paint of the present invention exhibit excellent interactions with microorganisms while remaining stable on the surface of the substrate, inhibiting the adhesion of microorganisms to the surface of the substrate. Even in the unlikely event that microorganisms do adhere to the surface of the substrate, they are able to inhibit the proliferation of microorganisms on the surface of the substrate and inhibit the formation of a biofilm on the surface of the substrate.

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 (11)

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;
An anti-biofilm agent characterized by containing a surfactant having an HLB value of 16 to 20. 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. The anti-biofilm agent according to claim 1 or 2, characterized in that the molecular weight of the acidic compound is 1,000 or less. The anti-biofilm agent according to claim 1 or 2, characterized in that the melting point of the surfactant is 30 to 230°C. The 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. The anti-biofilm agent according to claim 1 or 2, characterized in that a 0.5% by mass aqueous solution of the acidic compound has a pH of 4.2 or less at 25°C. The 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. The 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. 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;
An anti-biofilm resin composition comprising a synthetic resin. The anti-biofilm resin composition according to 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. 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;
An anti-biofilm paint comprising: