JP4841309B2 - Antibacterial agent - Google Patents

Description

  The present invention is a novel antibacterial agent or antibacterial agent that has excellent antibacterial properties against a wide range of microorganisms and is useful for a wide range of applications such as foods, cosmetics, pharmaceuticals, processing oils, cleaning agents, pharmaceuticals in manufacturing plants, and disinfectants. Relates to the composition.

In general, various antibacterial agents and preservatives are used in products such as foods, cosmetics, and pharmaceuticals in order to prevent deterioration of quality due to proliferation of microorganisms. In the fields of food, cosmetics and pharmaceuticals, sorbic acid, dehydroacetic acid, paraoxybenzoic acid derivatives, etc. are often used as antibacterial agents, but these substances may generate carcinogenic substances when mixed with nitrous acid. In recent years, safety has been questioned.
In addition, antibacterial agents and preservatives are also used in metalworking fluids and cleaning agents used in metalworking manufacturing plants in order to suppress the decay of these chemicals. The chemicals used in metal processing manufacturing plants are often used for a long period of time, and it is important to prevent quality degradation due to the growth of microorganisms during that period. Typical antibacterial agents used in drugs used in the metal processing field are isothiazoline and triazine types, but the former is highly irritating to the skin and the latter releases formaldehyde that worsens the work environment. Have problems such as.

  As antibacterial agents improved in terms of safety, those containing fatty acid monoglycerides as active ingredients are known, and are used as food shelf life improvers and food manufacturing environment antibacterial agents. In particular, fatty acid monoglycerides having 8 to 12 carbon atoms are widely used in the food field (Patent Documents 1 to 3). However, since the fatty acid monoglyceride has an ester bond structure, it does not have sufficient antibacterial properties against microorganisms.

Against the background of such current technical standards, antibacterial agents that are excellent in safety and effective against a wide range of microorganisms are desired.
JP-A-4-207179 JP-A-4-21608 Japanese Patent Laid-Open No. 3-67573 JP-A-7-126243

  Under the circumstances as described above, the problem to be solved by the present invention is to provide an antibacterial agent and an antibacterial composition that have excellent safety and effective antibacterial properties against a wide range of microorganisms and can be used in a wide range of applications. It is to be.

  The present inventor has conducted extensive research to solve the above problems, and has found that the general formula (1);

(In the formula, R represents a linear or branched aliphatic hydrocarbon group having 4 to 12 carbon atoms.)
It is found that the compound represented by the formula has effective antibacterial properties against a wide range of microorganisms, and when the compound and a chelating agent are used in combination, the antibacterial action is synergistically increased and the antibacterial spectrum is broadened. It was. This invention is completed based on such knowledge, and provides the antimicrobial agent and antimicrobial composition of the following aspects.
Item 1. The following general formula (1);

(In the formula, R represents a linear or branched aliphatic hydrocarbon group having 4 to 12 carbon atoms.)
An antibacterial agent comprising the compound represented by
Item 2. Item 2. The antibacterial agent according to item 1, wherein R is a linear or branched alkyl group having 4 to 12 carbon atoms.
Item 3. Item 3. An antibacterial composition comprising one or more antibacterial agents according to item 1 or 2.
Item 4. Item 4. The antibacterial composition according to item 3, further comprising one or more chelating agents.

  Since the antibacterial agent of the present invention is excellent in safety and has antibacterial activity against a wide range of microorganisms, it prevents the deterioration of the quality of food, cosmetics and pharmaceuticals, as well as processing oils and cleaning agents used in the industrial field. It is effective in inhibiting the decay of chemicals and maintaining the quality. In addition, the antibacterial agent of the present invention effectively suppresses the growth of a wider range of microorganisms including gram-negative bacteria because the antibacterial spectrum is further expanded and a synergistic effect is created in the antibacterial action when used in combination with a substance having a chelating effect. It is also effective in suppressing the growth of pathogenic bacteria such as MRSA.

  The compound represented by the above formula (1) of the present invention is a known substance and its production method is also known (Japanese Patent Laid-Open No. 7-126243). It is the property that was found. When the antibacterial agent of the present invention is a thioglycerin monoalkyl ether, the antibacterial agent can be obtained, for example, by using a commercially available alkyl bromide and thioglycerin as starting materials.

  In preferable embodiment of this invention, R in the compound shown by the said Formula (1) is a C4-C12 linear or branched aliphatic hydrocarbon group. Here, the aliphatic hydrocarbon group represents an alkyl group, an alkenyl group, and an alkynyl group. If the carbon number of the group represented by R is less than 4, sufficient bacteriostatic action against microorganisms cannot be obtained. On the other hand, when the number of carbon atoms in the group represented by R exceeds 12, the hydrophilicity is lost, so the stability in water is lowered and the antibacterial action is also lowered. Therefore, the preferable carbon number of the group represented by R is 6 to 12, and more preferably 8 to 12. In addition, the antibacterial composition of this invention may contain the antibacterial agent shown by 2 or more types which has the carbon number from which the group shown by R differs.

  Specific examples when the group represented by R is an alkyl group include linear or branched butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decanyl group, and undecyl group. And a dodecyl group. Specific examples when the group represented by R is an alkenyl group include linear or branched butenyl, pentenyl, hexenyl, heptynyl, octenyl, nonenyl, and decynyl groups. be able to.

  The content of the antibacterial agent of the present invention is not particularly limited because it is appropriately adjusted according to its use and form, but when used in a liquid, the minimum effective concentration is preferably 0.0001% by weight or more, preferably Is preferably contained in an amount of 0.005 to 1% by weight. If it is less than 0.005% by weight, a growth inhibitory effect cannot be obtained, and if it exceeds 1% by weight, a higher bacteriostatic effect proportional to the concentration cannot be obtained, which is not preferable.

  Moreover, the antibacterial agent of the present invention exhibits an antibacterial effect against gram-negative bacteria because the antibacterial action is synergistically enhanced and the antibacterial spectrum is broadened by using a chelating agent in combination. Examples of the chelating agent that can be used in combination with the antibacterial agent of the present invention include ethylenediaminetetraacetic acid, nitrilotriacetic acid, 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium. Salt, disodium edetate, trisodium edetate, tetrasodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, citric acid, ascorbic acid, succinic acid, adipic acid, suberic acid, edetic acid, etc. Can be mentioned. Ethylenediaminetetraacetic acid, nitrilotriacetic acid, succinic acid, adipic acid, and suberic acid are preferable.

  The usage and mode of use of the antibacterial agent of the present invention are not particularly limited as long as it is intended for antibacterial action against microorganisms. For example, foods, cosmetics, pharmaceuticals, medical cleaning agents, sterilizing cleaning agents for dishes, and oral use For example, it may be used in a detergent, an antibacterial agent for antibacterial processing on the surface of a synthetic resin, an antibacterial paint, a metal processing oil, or a cleaning agent after metal processing.

  Depending on the purpose of use as described above, the antibacterial agent of the present invention can be used in appropriate combination with other additives as long as the antibacterial action is not impaired. In a preferred embodiment, the antibacterial agent of the present invention further includes, for example, a cosmetic, a chelating agent, a rust preventive agent, a metal anticorrosive agent, an antifoaming agent, and the like further blended with a thickener, a humectant, a colorant, a fragrance and the like. Disinfecting / cleaning metalworking fluids and medical equipment and affected areas that further contain blended metalworking detergents, rust inhibitors, lubricants, extreme pressure additives, metal anticorrosives, antifoaming agents, dyes, fragrances, etc. It can be used as a medical cleaning fee.

  In addition to the above, the additives generally used in the field of antibacterial agents can be used in combination with the antibacterial agent of the present invention without any limitation as long as the antibacterial action of the antibacterial agent of the present invention is not impaired. Examples include surfactants, solvents, pH adjusters, and the like.

By using together with the above additives, the antibacterial agent of the present invention can be used as an antibacterial composition of various forms such as a solution, cream, paste, gel, gel, solid, powder and the like.
When the antibacterial agent or antibacterial composition of the present invention is used in foods, it can be blended with various commonly used ingredients such as animal and vegetable oils, sugars, salt, butter, margarine, seasonings. And blended with sweeteners.

  Below, the more specific example of the additive which can be used together with the antibacterial agent of this invention is enumerated.

  Examples of the surfactant include an anionic surfactant, a cationic surfactant, an amphoteric surfactant, and a nonionic surfactant.

  Examples of the anionic surfactant include fatty acid soaps (for example, sodium laurate, sodium palmitate, etc.), higher alkyl sulfates (for example, sodium lauryl sulfate, potassium lauryl sulfate, etc.), alkyl ether sulfates ( For example, POE-lauryl sulfate triethanolamine, POE-sodium lauryl sulfate, etc.), higher fatty acid amide sulfonate (eg, N-myristoyl-N-methyl taurine sodium, coconut oil fatty acid methyl tauride sodium, etc.), phosphate ester Salts (eg, POE-oleyl ether sodium phosphate, POE-stearyl ether phosphate, etc.), sulfosuccinates (eg, sodium di-2-ethylhexyl sulfosuccinate, lauryl polypropylene glycol sulfosuccinate) Sodium), alkylbenzene sulfonates (eg, sodium linear dodecyl benzene sulfonate, linear dodecyl benzene sulfonate triethanolamine, linear dodecyl benzene sulfonic acid, etc.), higher fatty acid ester sulfates (eg, hardened coconut oil fatty acid glycerin sulfate) Sodium), N-acyl glutamate (eg, monosodium N-lauroyl glutamate, disodium N-stearoyl glutamate, monosodium N-myristoyl-L-glutamate), sulfated oil (eg, funnel oil), POE -Alkyl ether carboxylic acid, POE-alkyl allyl ether carboxylic acid, α-olefin sulfonate, higher fatty acid ester sulfonate, higher fatty acid alkylolamide sulfate, etc. Can be mentioned.

  Examples of the cationic surfactant include alkyltrimethylammonium salts (eg, stearyltrimethylammonium chloride, lauryltrimethylammonium chloride, etc.), alkylpyridinium salts (eg, cetylpyridinium chloride, etc.), distearyldimethylammonium dialkyldimethylammonium chloride. Examples thereof include salts, alkyl quaternary ammonium salts, alkyl dimethyl benzyl ammonium salts, dialkyl morpholinium salts, POE-alkyl amines, alkyl amine salts, polyamine fatty acid derivatives, amino alcohol fatty acid derivatives, benzalkonium chloride, and benzethonium chloride.

  Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (eg, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide). Side-1-carboxyethyloxy disodium salt), betaine surfactants (for example, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkylbetaine, amide betaine) And sulfobetaine).

  Examples of the nonionic surfactant include sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate). Acid), glycerin polyglycerin fatty acids (eg glyceryl monoerucate, glyceryl sesquioleate, glyceryl monostearate), propylene glycol fatty acid esters (eg, propylene glycol monostearate), hardened castor oil derivatives, glycerin Alkyl ethers, POE-sorbitan fatty acid esters (for example, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitante) Laoleate, etc.), POE-sorbite fatty acid esters (eg, POE-sorbite monolaurate, POE-sorbite monooleate, POE-sorbite monostearate, etc.), POE-glycerin fatty acid esters (eg, POE-glycerin monostearate). Rate, POE-glycerin triisostearate, etc.), POE-fatty acid esters (eg, POE-distearate, POE-monodiolate, ethylene glycol distearate, etc.), POE-alkyl ethers (eg, POE-lauryl ether, POE-). Oleyl ether, POE-stearyl ether, etc.), pluronics, POE • POP-alkyl ethers (for example, POE • POP-cetyl ether, POE • POP-monobutyl ether, OE · POP-glycerin ether, etc.), Tetronics, POE-castor oil hardened castor oil derivatives (eg, POE-castor oil, POE-hardened castor oil, POE-hardened castor oil monoisostearate, etc.), alkanolamide ( For example, coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc.), POE-propylene glycol fatty acid ester, POE-alkylamine, POE-fatty acid amide, sucrose fatty acid ester and the like.

  Solvents include hydrocarbon solvents, higher alcohols (eg, lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, batyl alcohol, isostearyl alcohol), lower alcohols (eg, ethanol, isopropanol, t-butyl alcohol, etc.) , Polyhydric alcohols (eg, ethylene glycol, propylene glycol, trimethylene glycol, tetramethylene glycol, hexylene glycol, glycerin, trimethylolpropane, pentaerythritol, xylitol, sorbitol, diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol , Tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, poly Resin, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol benzyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, diethylene glycol Monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether Triethylene glycol monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene glycol butyl ether, ethylene glycol monomethyl ether acetate , Ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, pro Examples include pyrene glycol monoethyl ether acetate and propylene glycol monopropyl ether acetate.

  Examples of the pH adjuster include lactic acid, citric acid, succinic acid, carbonic acid, phosphoric acid, sodium hydroxide, potassium hydroxide and the like.

  Examples of thickeners include gum arabic, carrageenan, gum karaya, gum tragacanth, casein, dextrin, gelatin, sodium alginate, methylcellulose, ethylcellulose, CMC, hydroxyethylcellulose, hydroxypropylcellulose, PVA, sodium polyacrylate, guar gum, tamarind gum Xanthan gum, magnesium aluminum silicate, bentonite, hectorite, laponite and the like.

  Examples of the humectant include polyethylene glycol, propylene glycol, glycerin, xylitol, sorbitol, maltitol and the like.

  Examples of the colorant include titanium dioxide, zinc oxide, iron oxide, iron titanate, yellow iron oxide, ocher, black iron oxide, cobalt violet, cobalt titanate, ultramarine, pearl pigment, metal powder pigment, organic pigment, chlorophyll , Β-carotene and the like.

  Examples of the fragrances include musk, lime, sandalwood, mint, vanillin, citronellal, eugenol, linalool, coumarin, and ethyl cinnamate.

  Examples of the rust preventive agent include ptanol-alkanolamine salt of pt-butylbenzoic acid, metal salt of pt-butylbenzoic acid, alkanolamine salt of sebacic acid, metal salt of sebacic acid, alkanolamine salt of dodecanedioic acid, Examples include metal salts of dodecanedioic acid, alkanolamine salts of fatty acids having 5 to 20 carbon atoms, metal salts of fatty acids having 5 to 20 carbon atoms, alkanolamine salts of boric acid, and metal salts of boric acid.

  Examples of the metal anticorrosive include benzotriazole, tolyltriazole, 3-aminotriazole and the like.

  Examples of the antifoaming agent include silicone-based antifoaming agents.

  Examples of the lubricant include polyglycol synthetic lubricant.

  Extreme pressure additives include chlorinated paraffin, chlorinated fatty acid, chlorinated fatty oil, sulfurized olefin, sulfurized lard, alkylpolysulfide, sulfurized fatty acid, phosphate ester (salt), Examples thereof include phosphite ester (salt), thiophosphate ester (salt), phosphine, and tricresyl phosphate.

  Examples of the dye include Sudan III, quinoline yellow WS, fluorescein, quinizarin green SS, alizurin purple SS, Sudan blue B, and the like.

  The antibacterial agent of the present invention can be made into an antibacterial agent suitable for each purpose by appropriately using in combination with one or more of the additives listed above.

Examples 1-4 and Comparative Examples 1-7
Hereinafter, the present invention will be described in more detail with reference to examples. The present invention is not limited thereby.

As the antibacterial agent of the present invention in Examples 1, 2, 3 and 4, thioglycerin monoalkyl ether (TGAE) in which R is a linear alkyl group having 8, 9, 10 and 12 carbon atoms in the above formula (1) The following tests were carried out for each antibacterial property. TGAE was synthesized by dehydrobromination using alkyl bromide and thioglycerin as starting materials. Monocaprylin, monocaprin, monolaurin, 1,2-octanediol, 1,2-decanediol, and 1,2-dodecanediol are comparative antibacterial agents in Comparative Examples 1, 2, 3, 4, 5, and 6. Used (both manufactured by Tokyo Chemical Industry Co., Ltd.). Moreover, the thioglycerin monoalkyl ether whose R is C14 in the said Formula (1) was used as an antibacterial agent, and this was made into the comparative example 7.
Add various media (see below) to a 100 ml Erlenmeyer flask, add the above antibacterial agent or comparative antibacterial agent, inoculate with a test microorganism (see below), and incubate at 30 ° C. and 120 rpm for 3 days with shaking culture Then, the presence or absence of the growth of the bacteria was visually observed, and the concentration of each test substance (minimum growth inhibitory concentration: MIC) necessary for inhibiting the growth of the bacteria was determined.

  Microorganisms: Bacillus subtilis IFO3025, Candida utilis ATCC22023, baker's yeast (Saccharomyces cerevisiae ATCC9804), black mold (Aspergillus niger IFO4416) were used.

  Medium: Soybean / casein / digest medium (manufactured by Eiken Kikai Co., Ltd.) is used as the medium for fungi, and YM medium [yeast extract 3 g (manufactured by DIFCO)], malt extract 3 g (manufactured by DIFCO) ), Peptone 5 g (manufactured by DIFCO) and glucose 10 g (manufactured by Kanto Chemical Co., Ltd.) were dissolved in 1 L of water and adjusted to pH 4.5], and the potato dextrose medium (Sigma-Aldrich) was used as the filamentous fungus medium. Made).

  The results of Examples 1 to 4 and Comparative Examples 1 to 6 are shown in Tables 1 and 2, respectively.

Example 5
In formula (1) above, R is a thioglycerin monoalkyl ether (TGAE) having 6 to 10 carbon atoms and 12 carbon atoms as the antibacterial agent of the present invention, and a combination of two antibacterial agents and a chelating agent. The effect on antibacterial action was tested. TGAE was synthesized by dehydrobromination using alkyl bromide and thioglycerin as starting materials. As chelating agents, ethylenediaminetetraacetic acid (EDTA: manufactured by Dojindo Laboratories Co., Ltd.), nitrilotriacetic acid (NTA: manufactured by Kanto Chemical Co., Ltd.), succinic acid (manufactured by Kanto Chemical Co., Ltd.), adipic acid (manufactured by Kanto Chemical Co., Ltd.) ), Suberic acid (manufactured by Kanto Chemical Co., Inc.) was used.

  As a culture medium for bacteria, Soybean casein digest medium (manufactured by Eiken Equipment Co., Ltd.) is used, and the above-mentioned antibacterial agent and chelating agent are added to the prepared medium at the concentrations shown in Tables 3 and 4, and 100 ml volume is added. In addition to the Erlenmeyer flask, the following test microorganisms were inoculated, cultured by shaking at 30 ° C. and 120 rpm, and then the growth of the microorganisms was measured by absorbance at a wavelength of 650 nm. A low absorbance indicates that the growth of the microorganism is suppressed, and a high absorbance indicates that the growth of the microorganism is high. The results are shown in Tables 3 and 4. In addition, the compounding quantity of an antibacterial agent and a chelating agent shown by Table 3 and 4 is shown by ppm, and the used microorganisms are Pseudomonas aeruginosa IFO3080.

Comparative Example 8
The antibacterial action of each of the thioglycerin monoalkyl ether (TGAE) in which the carbon number of R in the formula (1) is 6 to 9 and the chelating agent alone was tested. Moreover, the antibacterial effect when monocaprylin, monocaprin, and monolaurin (all manufactured by Tokyo Chemical Industry Co., Ltd.) was used in combination with a chelating agent was tested. The results are shown in Table 5. In Table 5, the blending concentration of each antibacterial agent is shown in ppm. The microorganism used is Pseudomonas aeruginosa IFO3080.

  As mentioned above, it can be seen from the results of Examples and Comparative Examples shown in Tables 1 and 2 that the antibacterial agent of the present invention has a higher antibacterial action than glycerin monoalkyl ester and 1,2-alkanediol. Moreover, from the results shown in Tables 3 to 5, it can be seen that by using the antibacterial agent and the chelating agent of the present invention in combination, the antibacterial action is synergistically increased, and the gram-negative bacterium has high antibacterial properties.

Claims (4)

The following general formula (1);

(In the formula, R represents a linear or branched aliphatic hydrocarbon group having 4 to 12 carbon atoms.)
An antibacterial agent comprising the compound represented by The antibacterial agent according to claim 1, wherein R is a linear or branched alkyl group having 4 to 12 carbon atoms. An antibacterial composition comprising one or more antibacterial agents according to claim 1 or 2. The antibacterial composition according to claim 3, further comprising one or more chelating agents.