Anti-bromhidrosis agent

Abstract

To provide an agent against axillary odor bacteria that can effectively inhibit the growth of axillary odor bacteria.SOLUTION: The present invention provides an agent against axillary odor bacteria that contains 4-hydroxybenzoic acid ester represented by formula (1) or a salt thereof [where R1 is a C6 to 14 alkyl group].SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an antibacterial agent against Corynebacterium bacteria, which has an excellent growth inhibitory effect against Corynebacterium bacteria.

Background Art

[0002] Corynebacterium bacteria, also known as axillary osmidrosis bacteria, are known to cause axillary osmidrosis by decomposing apocrine sweat secreted from apocrine sweat glands in the axilla. Therefore, suppressing the growth and proliferation of Corynebacterium bacteria is effective in preventing axillary osmidrosis.

[0003] Patent Document 1 proposes an antibacterial composition containing a sucrose ester of a fatty acid and a paraoxybenzoic acid ester having 1 to 4 carbon atoms or a salt thereof. Further, Patent Document 2 proposes an antibacterial agent against Corynebacterium bacteria having methyl paraoxybenzoate as an active ingredient.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, parabens of lower alkyl esters having 1 to 4 carbon atoms proposed in Patent Document 1 did not have sufficient antibacterial activity against Corynebacterium bacteria.

[0006] Therefore, an agent having an excellent growth inhibitory effect against Corynebacterium genus (axillary osmidrosis bacteria) has been desired.

[0007] The object of the present invention is to provide an anti-bromhidrotic agent that has a high inhibitory effect on the growth of bromhidrosis bacteria. Another object of the present invention is to provide a method for preventing bromhidrosis that is excellent in inhibiting the growth of Corynebacterium species. [Means for solving the problem]

[0008] In view of the above problems, the inventors conducted diligent research and found that certain 4-hydroxybenzoic acid esters or their salts have a high inhibitory effect on the growth of axillary osmidrosis bacteria, thus completing the present invention.

[0009] In other words, the present invention encompasses the following preferred embodiments. [1] Formula (1) [ka] [In the formula, R1 represents an alkyl group having 6 to 14 carbon atoms.] An anti-bromhidrotic agent comprising a 4-hydroxybenzoic acid ester or a salt thereof, represented by [formula]. [2] The anti-bromhidrotic agent described in [2], wherein the bacterium causing the odor is a bacterium of the genus Corynebacterium. [3] The anti-bromhidrotic agent according to [1] or [2], wherein the 4-hydroxybenzoic acid ester represented by formula (1) is hexyl 4-hydroxybenzoate and / or ethylhexyl 4-hydroxybenzoate. [4] The 4-hydroxybenzoic acid ester represented by formula (1) is hexyl 4-hydroxybenzoate and ethylhexyl 4-hydroxybenzoate, as described in any of [1] to [3]. [5] A method for preventing the occurrence of body odor, comprising applying an anti-bromhidrotic agent described in any of [1] to [4] to a region or body to be treated. [Effects of the Invention]

[0010] The anti-bromhidrosis agent of the present invention provides a high inhibitory effect on the growth of bromhidrosis bacteria. [Modes for carrying out the invention]

[0011] The anti-bromhidrosis agent of the present invention contains a 4-hydroxybenzoic acid ester represented by formula (1) or a salt thereof as an active ingredient. [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 due to their superior inhibitory effect on the growth of odor-causing bacteria.

[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 an alkaline earth metal salt of the above 4-hydroxybenzoic acid ester. Specific examples of alkali metals include one or more selected from the group consisting of sodium, potassium, and lithium, and examples of alkaline earth metals include magnesium and / or calcium.

[0015] 4-hydroxybenzoic acid esters or their salts 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 because they have a superior inhibitory effect on the growth of axillary osmidrosis bacteria.

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

[0017] The anti-bromhidrosis bacteria agent of the present invention can be used in a form according to the purpose of use, and specifically, the following forms can be mentioned. (1) A form in which the 4-hydroxybenzoic acid ester represented by formula (1) or its salt is used alone as an anti-bromhidrosis bacteria agent as it is. (2) A form in which a solid preparation in which the 4-hydroxybenzoic acid ester represented by formula (1) or its salt is supported on a solid carrier is used as an anti-bromhidrosis bacteria agent. (3) A form in which 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-bromhidrosis bacteria agent. (4) A form in which a resin composition in which the 4-hydroxybenzoic acid ester represented by formula (1) or its salt is kneaded in a resin is used as an anti-bromhidrosis bacteria agent.

[0018] In the form in which the solid preparation supported on the solid carrier in (2) is used as an anti-bromhidrosis bacteria agent, examples of the solid carrier that can be used include minerals or inorganic powders such as kaolin, talc, bentonite, clay, diatomaceous earth, calcium carbonate, silica, zeolite, etc.; vegetable powders such as wood powder, soybean powder, wheat flour, starch, etc.; porous bodies such as PCP (porous coordination polymer), MOF (metal organic framework); plastics such as phenolic resin, polyamide, (meth)acrylic resin, polypropylene, polyester, etc.; synthetic fibers made of the plastics; rubber such as polybutadiene or its powder; sublimable powders such as camphor, naphthalene, paradichlorobenzene, trioxane, cyclododecane, adamantane, etc.; natural fibers such as linter, pulp, etc.; animal and plant fibers such as wool, cotton, silk, etc.; regenerated fibers such as rayon; inorganic fibers such as glass fiber, etc.

[0019] In the form in which a liquid formulation dissolved or dispersed in the solvent of (3) is used as an anti-bromhidrosis agent, examples of solvents that can be used include water, alcohols such as methyl alcohol, ethyl alcohol, ethylene glycol, propylene glycol, and butylene glycol; 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 form in which the resin composition kneaded into the resin of (4) is used as an anti-bromhidrosis agent, examples of resins to be used include thermoplastic resins, thermosetting resins, and rubbers.

[0021] Thermoplastic resins include polyethylene resins such as high-density polyethylene, medium-density polyethylene, low-density polyethylene, ultra-low-density polyethylene, and ultra-high molecular weight polyethylene; polypropylene resins; polyolefin resins such as ethylene-vinyl acetate copolymer resin and ethylene-methacrylic acid copolymer resin; chlorine resins such as vinyl chloride and vinylidene chloride homopolymer resin; styrene resins such as polystyrene and ABS (acrylonitrile butadiene styrene) resin; (meth)acrylic resins such as poly(meth)acrylate methyl; polyamide 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. Examples include polyether resins such as phenylene sulfide resin; 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 elastomers, polyolefin-based thermoplastic elastomers, polyvinyl chloride-based thermoplastic elastomers, and polyurethane-based thermoplastic elastomers; polycarbonate resins, thermoplastic polyimides, PSU (polysulfone) resins, plastomers, hydrolyzable resins, hydrated decomposition resins, and superabsorbent resins.

[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, melamineformaldehyde resins, phenolformaldehyde 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-based rubber, tetrafluoroethylene-propylene rubber, chlorosulfonated rubber, polysulfurized rubber, fluororubber, silicone rubber, and natural rubber.

[0024] These thermoplastic resins, thermosetting resins, and rubbers may be used individually or in combination of two or more. When using two or more in combination, they may be used as polymer alloys, blended, or laminated.

[0025] In all of the usage forms described in (1) to (4) above, other agents may be used in combination as necessary, such as various additives including antibacterial agents, disinfectants, antifungal agents, antiviral agents, colorants, plasticizers, antistatic agents, dispersants, reinforcing agents, surfactants, and fillers such as powder extenders. Furthermore, when used in combination with other agents, it is preferable from a safety standpoint that the amount (mass) used is equal to or less than the amount (mass) used of the 4-hydroxybenzoic acid ester or its salt represented by formula (1).

[0026] The anti-bromhidrotic agents described above can be prepared in the form of sprays, aerosols, pumps, liquids, ointments, patches, mats, sheets, tapes, powders, granules, gels, creams, films, containers, paints, fibers, pellets, and other dosage forms.

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

[0028] For example, when using an anti-bromhidrosis agent as a liquid formulation dissolved or dispersed in a solvent, a resin composition obtained by kneading with a resin, or a solid formulation supported on a solid carrier, it is preferable that the proportion of 4-hydroxybenzoic acid ester or its salt represented by formula (1) is preferably 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 formulation.

[0029] Examples of axillary osmidrosis bacteria whose growth should be inhibited by the anti-axillary osmidrosis agent of the present invention include Corynebacterium, Micrococcus, and Staphylococcus.

[0030] Among these, bacteria of the genus Corynebacterium are preferred because the anti-bromhidrosis agent of the present invention has a high inhibitory effect on the growth of bacterium that causes bacteriosclerosis.

[0031] Examples of fungi belonging to the genus Corynebacterium include Corynebacterium xerosis, Corynebacterium minutissimum, and Corynebacterium tenuis.

[0032] The anti-bromhidrosis agent of the present invention can be applied to a treatment area or body on which bromhidrosis bacteria can grow, or on which bromhidrosis bacteria may grow, to prevent the generation of malodor caused by the growth of bromhidrosis bacteria. In other words, the present invention also relates to a method for preventing or eliminating the generation or spread of malodor caused by the growth of bromhidrosis bacteria, which includes applying the above-mentioned anti-bromhidrosis agent to a treatment area or body on which bromhidrosis bacteria grow.

[0033] Examples of areas or objects to be treated include skin (surface), clothing such as underwear, shirts, shoes, socks, gloves, and hats, as well as handkerchiefs, towels, underarm sweat pads, and sweat wipes.

[0034] Methods for applying the anti-bromhidrotic agent of the present invention to the area to be treated include sprinkling, spraying, and coating, and methods for applying it to the object to be treated include kneading, sprinkling, spraying, coating, or impregnation. [Examples]

[0035] The present invention will be described in detail below with reference to examples, but the present invention is not limited thereto. The axillary osmidrosis bacteria used as test subjects in the examples and comparative examples are shown below.

[0036] <Bacteria targeted for testing for body odor> Axillary osmidrosis fungus: Corynebacterium xerosis (NBRC16721)

[0037] [Example 1] 0.02 g of hexyl 4-hydroxybenzoate, 500 μL of dimethyl sulfosoxide (DMSO), and 9.48 mL of sterile water were added to a sample tube and mixed for 1 minute using a vortex mixer to prepare a pre-adjusted solution (hexyl 4-hydroxybenzoate concentration 2000 ppm). In a 96-well (12 rows x 8 columns) microplate, 180 μL of pre-preparation solution was added to each well in the first row from the left, and 90 μL of sterile water was added to each well in the second to eleventh rows from the left. Next, 90 μL was taken from the first row from the left and added to the well to its right, diluting it to half its original volume. This procedure was repeated for the subsequent rows, preparing a solution containing hexyl 4-hydroxybenzoate at a concentration of 2000-2 ppm in the 96-well microplate. The remaining wells were then filled with only 90 μL of sterile water to create blanks. Soybean casein digest (SCD) medium (manufactured by Nissui Pharmaceutical Co., Ltd.), prepared to 67.5 g / L, was sterilized and 80 μL was dispensed into each well. Next, the bacterial suspension of the target axillary osmid bacteria, cultured in SCD medium at 30°C for 20 hours, was added to 10 3A suspension diluted with physiological saline to a cfu / mL concentration was added to each well at a concentration of 10 μL, and then incubated at 30°C for 48 hours. After visually confirming the growth of *Osmunda japonica* in the blank, the growth status of *Osmunda japonica* 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 Japanese Society of Chemotherapy standard method (micro-liquid dilution method).

[0038] [Example 2] The minimum inhibitory concentration was measured in the same manner as in Example 1, except that hexyl 4-hydroxybenzoate was replaced with ethylhexyl 4-hydroxybenzoate. The results are shown in Table 1.

[0039] [Example 3] The minimum inhibitory concentration was measured in the same manner as in Example 1, except that 0.02 g of hexyl 4-hydroxybenzoate was replaced with 0.01 g of hexyl 4-hydroxybenzoate and 0.01 g of ethylhexyl 4-hydroxybenzoate. The results are shown in Table 1. In addition, the FIC value (Fractional Inhibitory Concentration Index) was calculated from each MIC value using the following formula, and the combined effect was evaluated based on the evaluation criteria. The results of the FIC values ​​are shown in Table 2. FIC value = Qa / QA + Qb / QB Qa: What is the MIC value of component A when component A and component B are used together? QA: MIC value of component A alone, Qb: What is the MIC value of component B when component A and component B are used together? QB: MIC value of component B alone <Evaluation Criteria> FIC value < 1: Synergistic effect FIC value = 1: Additive effect FIC value > 1: Antagonistic effect

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

[0042] [Table 1] [Table 2]

[0043] As is clear from Table 1, the 4-hydroxybenzoic acid esters represented by formula (1) (Examples 1-3) are found to have excellent inhibitory effects on the growth of axillary osmidrosis bacteria and are useful as anti-axillary osmidrosis agents. Furthermore, as is clear from Table 2, it is found that the inhibitory effect on axillary osmidrosis bacteria is synergistically enhanced when used in combination with the 4-hydroxybenzoic acid esters shown in Example 3.

Claims

1. Formula (1) 【Chemistry 1】 [In the formula, R １ [This indicates an alkyl group with 6 to 14 carbon atoms.] An anti-bromhidrosis agent comprising a 4-hydroxybenzoic acid ester or a salt thereof, The bacteria that cause body odor are of the genus Corynebacterium, and this product shows an inhibitory effect on the growth of this bacterium. Anti-armpit odor agent.

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

3. The anti-bromhidrosis agent according to claim 2, wherein the 4-hydroxybenzoic acid ester represented by formula (1) is hexyl 4-hydroxybenzoate and ethylhexyl 4-hydroxybenzoate.

4. A method for preventing the occurrence of body odor, comprising applying the anti-bromhidrosis agent described in claim 1 to a region or body to be treated.

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