Anti-yeast agent

Abstract

To provide an anti-yeast agent that effectively inhibits the growth of yeast.SOLUTION: The present invention relates to an anti-yeast agent containing 4-hydroxybenzoic acid ester represented by formula (1) [where R1 is a C6 to 14 alkyl group] or a salt thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an anti-yeast agent having an excellent effect of inhibiting the growth of yeast. [Background technology]

[0002] In high humidity environments such as kitchens and bathrooms, bacteria can grow even in a relatively short time, causing slime to form. To remove the slime, frequent cleaning with chlorine-based chemicals or detergents containing surfactants is required. Therefore, it is preferable to prevent the formation of slime using chemicals that have excellent inhibitory effects on yeast growth.

[0003] Yeasts of the genus Rhodotorula are thought to be one of the bacteria that cause slime. Patent Document 1 proposes a slime-inhibiting composition that contains a slime-inhibiting component that has an antibacterial activity value against Rhodotorula of 2 or more, and reports that, for example, parahydroxybenzoic acid methyl ester and parahydroxybenzoic acid propyl ester have an antibacterial activity value against Rhodotorula of 2 or more. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2006-151908 Summary of the Invention [Problem to be solved by the invention]

[0005] However, the parabens such as parahydroxybenzoic acid methyl ester reported in Patent Document 1 do not have sufficient antibacterial activity against Rhodotorula.

[0006] Therefore, there has been a demand for an agent that has an excellent inhibitory effect on yeast growth.

[0007] An object of the present invention is to provide an anti-yeast agent having a high inhibitory effect on yeast growth. Another object of the present invention is to provide a method for preventing slime having an excellent inhibitory effect on yeast growth. [Means for solving the problem]

[0008] Means for Solving the Problems The present inventors have conducted extensive research in light of the above problems and have found that a specific 4-hydroxybenzoic acid ester or a salt thereof has a high growth inhibitory effect on yeast, thereby completing the present invention.

[0009] That is, the present invention includes the following preferred embodiments. [1] Formula (1) [ka] [wherein R1 represents an alkyl group having 6 to 14 carbon atoms] An anti-yeast agent comprising a 4-hydroxybenzoic acid ester represented by the formula: [2] The anti-yeast agent according to [1], wherein the yeast is a yeast of the genus Rhodotorula and / or Candida. [3] The anti-yeast agent according to [1] or [2], wherein the yeast is a yeast of the genus Rhodotorula. [4] The anti-yeast agent according to any one of [1] to [3], wherein the 4-hydroxybenzoic acid ester represented by formula (1) is hexyl 4-hydroxybenzoate and / or ethylhexyl 4-hydroxybenzoate. [5] The anti-yeast agent according to any one of [1] to [4], wherein the 4-hydroxybenzoic acid ester represented by formula (1) is hexyl 4-hydroxybenzoate and ethylhexyl 4-hydroxybenzoate. [6] A method for preventing slime formation, comprising applying the anti-yeast agent according to any one of [1] to [5] to a treatment area or a treatment body. [Effects of the Invention]

[0010] The anti-yeast agent of the present invention can provide a high growth inhibitory effect against yeast. DETAILED DESCRIPTION OF THE INVENTION

[0011] The anti-yeast agent of the present invention contains, as an active ingredient, a 4-hydroxybenzoic acid ester represented by formula (1) or a salt thereof. [ka] [In the formula, R1 represents an alkyl group having 6 to 14 carbon atoms.]

[0012] Specific examples of the 4-hydroxybenzoic acid ester represented by formula (1) used in the present invention include one or more selected from the group consisting of hexyl 4-hydroxybenzoate, heptyl 4-hydroxybenzoate, octyl 4-hydroxybenzoate, ethylhexyl 4-hydroxybenzoate, nonyl 4-hydroxybenzoate, decyl 4-hydroxybenzoate, isodecyl 4-hydroxybenzoate, undecyl 4-hydroxybenzoate, dodecyl 4-hydroxybenzoate, tridecyl 4-hydroxybenzoate, and tetradecyl 4-hydroxybenzoate.

[0013] Among these, hexyl 4-hydroxybenzoate and / or ethylhexyl 4-hydroxybenzoate are more preferably used because of their excellent inhibitory effect on yeast growth.

[0014] The salt of the 4-hydroxybenzoic acid ester represented by formula (1) used in the present invention is preferably an alkali metal salt or alkaline earth metal salt of the 4-hydroxybenzoic acid ester. Specific examples of the alkali metal include one or more selected from the group consisting of sodium, potassium, and lithium, and specific examples of the alkaline earth metal include magnesium and / or calcium.

[0015] The 4-hydroxybenzoic acid esters or salts thereof may be used alone or in combination of two or more. It is preferable to use hexyl 4-hydroxybenzoate and ethylhexyl 4-hydroxybenzoate in combination, as this has a more excellent effect of inhibiting yeast growth.

[0016] The 4-hydroxybenzoic acid ester or its salt used in the present invention may be a commercially available product, or may be a product obtained by reacting 4-hydroxybenzoic acid with an aliphatic alcohol in the presence of a catalyst, as described in JP 2018-95581 A.

[0017] The anti-yeast agent of the present invention can be used in a form depending on the purpose of use, and specific examples thereof include the following forms. (1) A form in which the 4-hydroxybenzoic acid ester represented by formula (1) or a salt thereof is used alone as an anti-yeast agent. (2) A solid preparation in which the 4-hydroxybenzoic acid ester represented by formula (1) or a salt thereof is supported on a solid carrier is used as an anti-yeast agent. (3) A liquid preparation in which the 4-hydroxybenzoic acid ester represented by formula (1) or its salt is solubilized or dispersed in a solvent is used as an anti-yeast agent. (4) A resin composition obtained by kneading a 4-hydroxybenzoic acid ester represented by formula (1) or a salt thereof into a resin is used as an anti-yeast agent.

[0018] In the form of (2) where the solid preparation supported on a solid carrier is used as an anti-yeast agent, examples of usable solid carriers include mineral or inorganic powders such as kaolin, talc, bentonite, clay, diatomaceous earth, calcium carbonate, silica, and zeolite; vegetable powders such as wood flour, soybean flour, wheat flour, and starch; porous materials such as PCP (porous coordination polymer) and MOF (metal-organic framework); plastics such as phenolic resin, polyamide, (meth)acrylic resin, polypropylene, and polyester; synthetic fibers made of such plastics; rubbers such as polybutadiene or powders thereof; sublimable powders such as camphor, naphthalene, paradichlorobenzene, trioxane, cyclododecane, and adamantane; natural fibers such as linters and pulp; animal and vegetable fibers such as wool, cotton, and silk; regenerated fibers such as rayon; and inorganic fibers such as glass fiber.

[0019] In the case where the anti-yeast agent is a liquid preparation dissolved or dispersed in a solvent (3), solvents that can be used include alcohols such as water, methyl alcohol, ethyl alcohol, ethylene glycol, propylene glycol, butylene glycol, etc.; ketones such as acetone and methyl ethyl ketone; ethers such as tetrahydrofuran and dioxane; aliphatic hydrocarbons such as hexane, kerosene, and paraffin; aromatic hydrocarbons such as benzene, toluene, and xylene; and esters such as ethyl acetate and hexyl laurate; and aprotic polar solvents such as dimethyl sulfoxide, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and acetonitrile.

[0020] In the embodiment (4) where the resin composition kneaded into a resin is used as an anti-yeast agent, examples of the resin to be used include thermoplastic resins, thermosetting resins and rubbers.

[0021] Thermoplastic resins include polyethylene-based resins such as high-density polyethylene, medium-density polyethylene, low-density polyethylene, very-low-density polyethylene, and ultra-molecular-weight polyethylene; polypropylene-based resins; polyolefin-based resins such as ethylene-vinyl acetate copolymer resin and ethylene-methacrylic acid copolymer resin; chlorine-based resins such as vinyl chloride and vinylidene chloride homopolymer vinylidene chloride resins; styrene-based resins such as polystyrene and ABS (acrylonitrile butadiene styrene) resin; (meth)acrylic resins such as polymethyl (meth)acrylate; polyamide-based resins such as nylon 6 and nylon 66; polyacetal resin, PPE (polyphenylene ether) resin, PEI (polyetherimide) resin, PES (polyethersulfone) resin, modified PPE resin, PPS (polyphenylene ether) resin, etc. thermoplastic polyester resins such as PET (polyethylene terephthalate) resin, PBT (polybutylene terephthalate) resin, PEN (polyethylene naphthalate), PBN (polybutylene naphthalate) resin, and LCP (liquid crystal polymer) resin; fluororesins such as PVF (polyvinyl fluoride) resin; polyether ketone resins such as PEEK (polyether ether ketone) resin; thermoplastic elastomer resins such as styrene-based thermoplastic elastomer, polyolefin-based thermoplastic elastomer, polyvinyl chloride-based thermoplastic elastomer, and polyurethane-based thermoplastic elastomer; polycarbonate resin, thermoplastic polyimide, PSU (polysulfone) resin, plastomer, hydrolyzable resin, hydration-decomposable resin, and water-absorbent resin.

[0022] Examples of thermosetting resins include epoxy resins, unsaturated polyester resins, phenolic resins, urea resins, melamine resins, polyurethane resins, silicone resins, diallyl phthalate resins, alkyd resins, guanamine resins, polyimide resins, urea resins, melamine formaldehyde resins, phenol formaldehyde resins, furan resins, and xylene resins.

[0023] Examples of rubbers include butyl rubber, isoprene rubber, SBR (styrene butadiene rubber), NIR (nitrile isoprene rubber), NBR (nitrile butadiene rubber), urethane rubber, chloroprene rubber, EPDM (ethylene propylene diene copolymer rubber), EPM (ethylene propylene copolymer rubber), butadiene rubber, acrylic rubber, chlorinated polyethylene, epichlorohydrin rubber, propylene oxide rubber, ethylene-acrylic rubber, norbornene rubber, hydrogenated nitrile rubber, polyether rubber, tetrafluoroethylene-propylene rubber, chlorosulfonated rubber, polysulfide rubber, fluororubber, silicone rubber, and natural rubber.

[0024] These thermoplastic resins, thermosetting resins, and rubbers may be used alone or in combination of two or more thereof. When two or more thereof are used in combination, they may be used as a polymer alloy, a blend, or a laminate of the respective resin layers.

[0025] In any of the above use forms (1) to (4), other agents may be used in combination as needed, for example, various additives such as antibacterial agents, bactericides, antifungal agents, insecticides, anti-algae agents, colorants, flame retardants, heat stabilizers, plasticizers, light stabilizers (e.g., ultraviolet absorbers), antistatic agents, dispersants, and release agents, as well as fillers such as reinforcing agents, surfactants, and powder extenders. When other agents are used in combination, it is preferable, from the viewpoint of safety, that the amount (by mass) of the other agents used be equal to or less than the amount (by mass) of the 4-hydroxybenzoic acid ester represented by formula (1) or its salt used.

[0026] The anti-yeast agent in the above-mentioned form can be prepared into dosage forms such as sprays, aerosols, pumps, liquids, liniments, patches, matting agents, sheets, tapes, powders, granules, gels, creams, films, containers, paints, fibers, and pellets.

[0027] In the anti-yeast agent of the present invention, the content of the 4-hydroxybenzoic acid ester represented by formula (1) or its salt can be appropriately determined depending on the formulation, application method, and application location of the anti-yeast agent.

[0028] For example, when the anti-yeast agent is used as a liquid preparation dissolved or dispersed in a solvent, a resin composition obtained by kneading with a resin, or a solid preparation supported on a solid carrier, the 4-hydroxybenzoic acid ester represented by formula (1) or its salt is preferably contained in an amount of 0.0001 to 50% by mass, more preferably 0.001 to 30% by mass, and even more preferably 0.01 to 20% by mass relative to the mass of each preparation.

[0029] The yeasts whose growth is to be inhibited by the anti-yeast agent of the present invention include those of the genus Rhodotorula, Sporobolomyces, Pseudozyma, Ustilago, Saccharomyces, Candida, Torulopsis, Zygosaccharomyces, and the like. ), Schizosaccharomyces, Pichia, Yarrowia, Hansenula, Kluyveromyces, Debaryomyces, Geotrichum, Wickerhamia, and Fellomyces are examples of such genera.

[0030] Among these, yeasts of the genus Rhodotorula and / or Candida are preferred because the antiyeast agent of the present invention has a high inhibitory effect on yeast growth, and yeasts of the genus Rhodotorula are more preferred because they have a high slime-inhibiting effect.

[0031] Examples of yeasts belonging to the genus Rhodotorula include Rhodotorula glutinis, Rhodotorula minuta, Rhodotorula mucilaginosa, and Rhodotorula slooffiae.

[0032] Examples of yeasts in the genus Candida include Candida bombicola, Candida albicans, Candida dubliniensis, Candida guiliermondii, Candida parapsilosis, Candida pelliculosa, Candida tropicalis, Candida etchellsii, Candida versatilis, Candida stellate, Candida tropicalis, and Candida utilis.

[0033] The anti-yeast agent of the present invention can be applied to a treated area or object where yeast can grow or where slime may develop due to yeast growth, thereby preventing the development of slime due to yeast growth. That is, the present invention also relates to a method for preventing or eliminating the development or spread of slime due to yeast growth, which comprises applying the anti-yeast agent to a treated area or object.

[0034] The treated area or object can be suitably applied to kitchens, bathrooms, sinks, mirrors, and toilet-related items that are exposed to high humidity environments. Specific examples include bathroom building materials such as tiles and packing.

[0035] The anti-yeast agent of the present invention can be applied to the area to be treated by methods such as scattering, spraying, and coating, and can be applied to the object to be treated by methods such as kneading, scattering, spraying, coating, and impregnation. [Example]

[0036] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. The yeasts tested in the examples and comparative examples are shown below.

[0037] <Tested yeast species> Yeast 1: Rhodotorula mucilaginosa NBRC0382 Yeast 2: Candida albicans NBRC1594

[0038] [Example 1] 0.02 g of hexyl 4-hydroxybenzoate, 500 μL of dimethyl sulfoxide (DMSO), and 9.48 mL of sterile water were placed in a sample tube and stirred for 1 minute using a vortex mixer to prepare a pre-adjusted solution (hexyl 4-hydroxybenzoate concentration: 2000 ppm). 180 μL of the pre-adjusted solution was added to each well in the first column from the left of a 96-well (12 columns x 8 rows) microplate, and 90 μL of sterile water was added to each well in the second to eleventh columns from the left. Next, 90 μL of the solution was taken from the well in the first column from the left and added to the well immediately to the right, diluting it by half. This procedure was repeated for the second column and subsequent columns, preparing solutions containing hexyl 4-hydroxybenzoate at concentrations of 2000 to 2 ppm in the 96-well microplate. The remaining wells were filled with 90 μL of sterile water alone to serve as blanks. Soybean casein digest (SCD) medium (manufactured by Nissui Pharmaceutical Co., Ltd.) adjusted to 67.5 g / L was sterilized and then dispensed in 80 μL portions into all wells. Next, yeast 1 was cultured in SCD medium at 30°C for 20 hours, and the resulting bacterial solution was added to 10 3A suspension diluted with saline to a concentration of cfu / mL was added to each well in an amount of 10 μL, followed by incubation at 30°C for 72 hours. After visually confirming that yeast had grown in the blank, the yeast growth in each well was visually observed, and the minimum inhibitory concentration (MIC: μg / mL) was measured. The results are shown in Table 1. The minimum inhibitory concentration was measured according to the standard method of the Japanese Society of Chemotherapy (broth microdilution method).

[0039] [Example 2] The minimum inhibitory concentration was measured in the same manner as in Example 1, except that hexyl 4-hydroxybenzoate was changed to ethylhexyl 4-hydroxybenzoate. The results are shown in Table 1.

[0040] [Comparative Example 1] The minimum inhibitory concentration was measured in the same manner as in Example 1, except that hexyl 4-hydroxybenzoate was changed to methyl 4-hydroxybenzoate. The results are shown in Table 1.

[0041] Comparative Example 2 The minimum inhibitory concentration was measured in the same manner as in Example 1, except that hexyl 4-hydroxybenzoate was changed to ethyl 4-hydroxybenzoate. The results are shown in Table 1.

[0042] Comparative Example 3 The minimum inhibitory concentration was measured in the same manner as in Example 1, except that hexyl 4-hydroxybenzoate was changed to propyl 4-hydroxybenzoate. The results are shown in Table 1.

[0043] Comparative Example 4 The minimum inhibitory concentration was measured in the same manner as in Example 1, except that butyl 4-hydroxybenzoate was used instead of hexyl 4-hydroxybenzoate. The results are shown in Table 1.

[0044] Comparative Example 5 The minimum inhibitory concentration was measured in the same manner as in Example 1, except that hexyl 4-hydroxybenzoate was changed to hexadecyl 4-hydroxybenzoate. The results are shown in Table 1.

[0045] [Table 1]

[0046] [Example 3] The minimum inhibitory concentration was measured in the same manner as in Example 1, except that the test yeast was changed to yeast 2. The results are shown in Table 2.

[0047] [Example 4] The minimum inhibitory concentration was measured in the same manner as in Example 3, except that hexyl 4-hydroxybenzoate was changed to ethylhexyl 4-hydroxybenzoate. The results are shown in Table 2.

[0048] [Example 5] The minimum inhibitory concentration was measured in the same manner as in Example 3, except that 0.02 g of hexyl 4-hydroxybenzoate was changed to 0.01 g of hexyl 4-hydroxybenzoate and 0.01 g of ethylhexyl 4-hydroxybenzoate. The results are shown in Table 2.

[0049] Comparative Example 6 The minimum inhibitory concentration was measured in the same manner as in Example 3, except that hexyl 4-hydroxybenzoate was changed to methyl 4-hydroxybenzoate. The results are shown in Table 2.

[0050] Comparative Example 7 The minimum inhibitory concentration was measured in the same manner as in Example 3, except that hexyl 4-hydroxybenzoate was changed to hexadecyl 4-hydroxybenzoate. The results are shown in Table 2.

[0051] [Table 2]

[0052] For Example 5, the FIC value (Fractional Inhibitory Concentration Index: index of combined effect) was calculated from each MIC value using the following formula, and the combined effect was evaluated based on the evaluation criteria. The FIC value results are shown in Table 3. FIC value = Qa / QA + Qb / QB Qa: MIC value of component A when component A and component B are used together QA: MIC value of component A alone Qb: MIC value of component B when component A and component B are used together QB: MIC value of B component alone <Evaluation criteria> FIC value < 1: synergistic effect FIC value = 1: additive effect FIC value > 1: antagonistic effect

[0053] [Table 3]

[0054] As is clear from Tables 1 and 2, the 4-hydroxybenzoic acid esters represented by formula (1) (Examples 1 to 5) have excellent inhibitory effects on the growth of yeasts and are useful as anti-yeast agents. Furthermore, as is clear from Table 3, it is understood that the combined use of the 4-hydroxybenzoic acid esters shown in Example 5 synergistically improves the inhibitory effect on the growth of yeasts.

Claims

1. Formula (1) 【Chemistry 1】 [In the formula, R １ represents an alkyl group having 6 to 14 carbon atoms. An anti-yeast agent comprising a 4-hydroxybenzoic acid ester represented by the formula: An anti-yeast agent, wherein the yeast is a yeast of the genus Rhodotorula and / or Candida.

2. The anti-yeast agent according to claim 1, wherein the yeast is a yeast of the genus Rhodotorula.

3. 3. The anti-yeast agent according to claim 1, wherein the 4-hydroxybenzoic acid ester represented by formula (1) is hexyl 4-hydroxybenzoate and / or ethylhexyl 4-hydroxybenzoate.

4. The anti-yeast agent according to claim 3, wherein the 4-hydroxybenzoic acid ester represented by formula (1) is hexyl 4-hydroxybenzoate or ethylhexyl 4-hydroxybenzoate.

5. A method for preventing slime formation, comprising applying the anti-yeast agent according to claim 1 to a treated area or object.

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