WO2015122364A1

WO2015122364A1 - Synergistic bactericidal/antibacterial and antifungal composition

Info

Publication number: WO2015122364A1
Application number: PCT/JP2015/053351
Authority: WO
Inventors: 眞由美古川; 和彦坂田
Original assignee: ロンザジャパン株式会社
Priority date: 2014-02-14
Filing date: 2015-02-06
Publication date: 2015-08-20
Also published as: CN106028818A; JPWO2015122364A1

Abstract

A synergistic antibacterial and antifungal composition characterised by containing (A) 2-methyl-4,5-trimethylene-4-isothiazoline-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate and/or (C) benzoic acid and/or an alkali metal salt thereof has an immediate sterilisation effect on microorganisms, moreover has an excellent antiseptic effect, and is capable of synergistically controlling microorganisms. The synergistic antibacterial and antifungal composition is suitable for use in: a non-woven fabric, a textile product, a wet wipe to be used as a paper wet towel, a wet tissue, a hand wipe, a sanitary wipe or the like; a home or vehicle perfuming agent; a deodorising agent; a toilet liquid cleaning agent; an antifouling agent; or a cosmetic product such as a lotion, a cream, or a soap.

Description

Synergistic sterilization / antibacterial / antifungal composition

The present invention is particularly used for non-woven fabrics, textile products, paper towels, wet tissues, wipes, wet wipe sheets, etc., wet wiper applications, household and car fragrances, deodorants, toilet liquid cleaners, antifouling agents In addition, it is used for antiseptic purposes in order to prevent cosmetics such as lotions, creams, soaps, etc. from deteriorating or decaying due to microbial contamination. A composition for synergistically controlling microorganisms by imparting antibacterial and antifungal properties, particularly comprising 2-methyl-4,5-trimethylene-4-isothiazolin-3-one as a bactericidal agent, The present invention relates to a synergistic antibacterial and antifungal composition.

Conventionally, bactericides and preservative compositions have been used in many fields of general industrial water-based products, and are used to control harmful microorganisms such as bacteria, molds, yeasts or algae. Among them, isothiazoline compounds have long been known as highly effective disinfectants and preservatives.

2-Methyl-4,5-trimethylene-4-isothiazolin-3-one and 3-iodo-2-propynyl-N-butylcarbamate are emulsions, latexes, water-based paints, water-based inks, paper coating agents, starch paste, Bactericidal and antiseptic, added to pigment slurries, concrete admixtures, cooling water, water treatment, water-based general household products, agricultural chemicals, wood and other industrial products to prevent product deterioration and spoilage caused by microorganisms such as bacteria and fungi It is an antifungal agent and has been used for general industrial purposes since ancient times.

In isothiazolin-3-one, a compound having a high antiseptic effect has been used for general industrial purposes since ancient times. Among these compounds, 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methylisothiazolin-3-one, and 1,2-benzisothiazolin-3-one are known. Insufficient bactericidal and antiseptic effects on microorganisms, lack of sustainability, poor stability under conditions of high pH and in the presence of nucleophiles, oxidants and reducing agents Has the following points.

It is already known to use isothiazoline compounds in combination.
Patent Document 1 (Japanese Patent No. 2029853) includes a mixture of 5-chloro-2-methylisothiazolin-3-one / 2-methyl-4-isothiazolin-3-one and 1,2-benzisothiazolin-3-one. An industrial disinfectant / preservative composition is disclosed.

Patent Document 2 (Japanese Patent Laid-Open No. 9-77616) describes 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and halogenated oxime compounds (dichloroglyoxime, α-chlorobenzaldoxime, α-chloro). Benzaldoxime acetate, 4-hydroxyphenyl-α-ketoacetohydroxymic acid chloride), halogenated thiophene compound (3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide, 3,3,4, 4-tetrabromotetrahydrothiophene-1,1-dioxide) or halogenated dithiol compound (4,5-dichloro-1,2-dithiol-3-one, 5-chloro-4-phenyl-1,2-dithiol-3) Disinfectant compositions combining -on) are disclosed.

Patent Document 3 (US Pat. No. 5,328,926) discloses a synergistic composition obtained by combining 1,2-benzisothiazolin-3-one and an iodopropargyl compound (iodopropynyl compound). As such a compound, 3-iodo-2-propynyl-N-butyl carbamate is disclosed.

Patent Document 4 (Japanese Patent 4520042) and Patent Document 5 (International Patent Application PCT / EP1999 / 006056) include 2-methyl-4-isothiazolin-3-one and 3-iodo-2-propynyl-N-butylcarbamate. A combined synergistic bactericidal composition is disclosed.

These are conventionally used mainly in general industrial applications, and are already known as preservatives that synergistically provide an antiseptic effect. Similarly, wet wiper use for non-woven fabrics, textile products, paper towels, wet tissues, hand towels, wipe sheets, etc., home and car fragrances, deodorants, toilet liquid cleaners, antifouling agents and lotions, Even cosmetics such as creams and soaps are safe from being damaged by microorganisms such as bacteria and fungi, causing physical deterioration and aesthetic defects, thereby reducing the value of the product. Various drugs have been used that meet the cosmetics standards that combine sex.

For example, it is disclosed in Patent Document 6 (Japanese Patent Laid-Open No. 10-219282) and Patent Document 7 (Japanese Patent 2981451) that benzoic acid and sodium benzoate are excellent in antiseptic effect.

However, a single preparation lacks long-term effects, lacks efficacy, or easily causes the emergence of resistant bacteria. As a means for solving these problems, it is added in a synergistic effect by combining two or three components. It has become common to use in a tendency to reduce the amount.

However, recently, as a result of the establishment of new test methods that serve as numerical values and indicators for the standards of antibacterial, sterilizing and bactericidal effects of products, it has been applied to nonwoven fabrics, textile products, paper towels, wet tissues, towels, wipes For wet wiper use, household and car fragrances, deodorants, toilet liquid cleaners, antifouling agents and lotions, creams, soaps, and other cosmetics that differentiate the products that are effective against specific microorganisms Tend to be noticeable. Under such circumstances, the market will increase efficacy by further effective combination, secure safety by reducing the amount of drug added, antiseptic, antibacterial, sterilization by combination of drugs with wider spectrum Products with antifungal effects are expected.

Japanese Patent No. 2029853 Japanese Patent Laid-Open No. 9-77616 US Pat. No. 5,328,926 Japanese Patent No. 4520042 International Patent Application PCT / EP1999 / 006056 JP-A-10-219282 Japanese Patent No. 2981451

The purpose of the present invention is to expand the antibacterial spectrum compared to the synergistic action of the antiseptic effect by the conventional combination, and in addition to the conventional antiseptic purpose, more effective antibacterial, antibacterial and antifungal agents can be expected. Is to provide. More specifically, the object of the present invention is to make the active ingredient used synergistically, so that the active ingredient is compared to the required concentration when used in a single formulation or an already known combination. Can be used at lower concentrations, thus reducing the extent to which people and the environment are exposed to contamination, reducing costs, and having a wider spectrum, so the antiseptic effect is maintained over a long period of time It is to provide a synergistic antibacterial / antifungal composition having characteristics such that it can be expected to have a sterilizing effect that is immediately effective against microorganisms, particularly when added to an aqueous product.

This object is achieved by the synergistic fungicidal and antifungal composition of the present invention having antibacterial active isothiazoline compounds, one of which is 2-methyl-4,5-trimethylene-4-isothiazolin-3-one. Is done. The synergistic fungicidal and antifungal composition of the present invention comprises (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and (C) A synergistic antibacterial and antifungal composition comprising benzoic acid and / or an alkali metal salt thereof.

More specifically, the present invention relates to the following.
[1] (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid and / or A synergistic antibacterial / antifungal composition comprising the alkali metal salt.
[2] (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or its alkali The synergistic antibacterial / antifungal composition according to [1], wherein the weight ratio (A) :( B) :( C) of the metal salt is 100 to 1: 1 to 50: 0.
[3] (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or its alkali The synergistic antibacterial and antifungal composition according to [1], wherein the weight ratio (A) :( B) :( C) of the metal salt is 100 to 1: 0 to 1 to 100.
[4] (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or its alkali The synergistic antibacterial / antifungal composition according to [1], wherein the weight ratio (A) :( B) :( C) of the metal salt is 100 to 1: 1 to 50: 1 to 100.
[5] More preferably, (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and The synergistic antibacterial / antifungal composition according to [1], wherein the weight ratio (A) :( B) :( C) of the alkali metal salt thereof is 15 to 1: 1 to 10: 0 object.
[6] More preferably, (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and The synergistic antibacterial / antifungal composition according to [1], wherein the weight ratio (A) :( B) :( C) of the alkali metal salt thereof is 15 to 1: 0 to 1 to 100 object.
[7] More preferably, (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and The synergistic antibacterial / antimicrobial agent according to [1], wherein the weight ratio (A) :( B) :( C) of the alkali metal salt is 15 to 1: 1 to 10: 1 to 100 Mold composition.
[8] For non-woven fabrics, textile products, paper towels, wet tissues, hand wipes, wet wipes used for wipe sheets, household or car fragrances, deodorants, toilet liquid cleaners, antifouling agents or cosmetics The synergistic antibacterial / antifungal composition according to any one of [1] to [7].
[9] (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid and / or The total active ingredients of the alkali metal salts are nonwoven fabrics, textile products, paper towels, wet tissues, towels, wet wipes used for wipes, home or car fragrances, deodorants, toilet liquid cleaning The synergistic antibacterial / antibacterial agent according to any one of [1] to [7], which is blended in a proportion of 0.002 wt% or more and 1.5 wt% or less in an agent, antifouling agent or cosmetic. Anti-fungal composition.
[10] More preferably, (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid The total of the active ingredients that are acids and / or alkali metal salts thereof are nonwoven fabrics, textile products, paper towels, wet tissues, wipes, wet wipes used for wipe sheets, household or car fragrances, deodorants, As described in any one of [1] to [7], which is blended in a liquid cleaning agent, an antifouling agent or a cosmetic of a toilet at a ratio of 0.005% by weight or more and 1.0% by weight or less. Synergistic antibacterial and antifungal composition.
[11] A wet wiper for use in a nonwoven fabric, a textile product, a paper towel, a wet tissue, a towel, a towel wipe, and a non-woven fabric containing the synergistic antibacterial / antifungal composition according to any one of [1] to [7] Home or car fragrance, deodorant, toilet liquid cleaner, antifouling agent or cosmetic.
[12] (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid and / or The non-woven fabric, textile product, paper towel, wet tissue, towel, and the like as described in [11], wherein the total of active ingredients which are alkali metal salts is blended in a proportion of 0.002 wt% or more and 1.5 wt% or less. Wet wipers used for wiping sheets, household or car fragrances, deodorants, toilet liquid cleaners, antifouling agents or cosmetics.
[13] More preferably, (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid The nonwoven fabric, textile product, paper towel, wet tissue according to [11], wherein the total of active ingredients which are acids and / or alkali metal salts thereof is blended in a proportion of 0.005 wt% to 1.0 wt% , Wet wipes used for wipes, wipes for wipes, household or car fragrances, deodorants, toilet liquid cleaners, antifouling agents or cosmetics.
[14] Manufacture of non-woven fabrics, textile products, paper towels, wet tissues, hand towels, wet wipes used for wipes, wipes for homes or cars, deodorants, toilet liquid cleaners, antifouling agents or cosmetics Use of the synergistic antibacterial / antifungal composition according to any one of [1] to [7].

The synergistic antibacterial and antifungal composition of the present invention is used for non-woven fabrics, textile products, paper towels, wet tissues, wipes, wipes for wet wipes, home and car fragrances, deodorants, toilets In order to prevent cosmetics such as liquid detergents, antifouling agents and lotions, creams, soaps, etc. It has a high fungal effect, provides excellent antibacterial and antifungal properties, exhibits a synergistic antiseptic effect, and is effective in preventing various problems caused by microorganisms. In addition, it is a useful synergistic antibacterial and antifungal composition that has low toxicity, no pollution concerns, and does not adversely affect the target composition.

2-Methyl-4,5-trimethylene-4-isothiazolin-3-one, which is one of the components of this composition, includes, for example, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl Less skin irritation than -4-isothiazolin-3-one. In addition, it is an antibacterial active substance that is environmentally friendly. By using this compound as one of the components of this composition, it does not have the disadvantage of causing allergies to the user, and it is in industrial wastewater. It has the advantage that it is very easy to handle in terms of legal regulations.

In the synergistic antibacterial and antifungal composition of the present invention, (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and (C) The weight ratio (A) :( B) :( C) of benzoic acid and / or alkali metal salt thereof is preferably 100-1: 1-50: 0, 100-1: 0: 1-100 Or 100 to 1: 1 to 50: 1 to 100, more preferably 15 to 1: 1 to 10: 0, 15 to 1: 0 to 1 to 100, or 15 to 1: 1 to 10: 1. ~ 100.

In the synergistic antibacterial and antifungal composition of the present invention, (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N which are active ingredients -Butyl carbamate and / or (C) benzoic acid and / or alkali metal salts thereof are used for wet wipers used in nonwoven fabrics, textile products, paper towels, wet tissues, wipes, wipes, etc. Fragrance, deodorant, toilet liquid cleaner, antifouling agent and lotion, cream, soap, and other cosmetics, 0.002% to 1.5% by weight, more preferably 0.005% by weight It is blended (added) at a ratio of 1.0% by weight or less.

In the synergistic antibacterial and antifungal composition of the present invention, (B) 3-iodo-2-propynyl-N-butyl carbamate is included in an inclusion compound such as cyclodextrin (α-form, β-form, γ-form). You may use what has been.

If necessary, a hydrophilic solvent can be used as the solubilizer of the present invention. Preferred hydrophilic solvents are ethanol, isopropanol, glycerin, ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, hexylene glycol, butylene glycol (1,3-butylene glycol, 1,2-butylene glycol, 1, 4-butylene glycol), propylene glycol monocaprylate, polyethylene glycol caprylate, and the like.

In addition to these, hydrophilic surfactants as solubilizers include polyoxyethylene hydrogenated castor oil, polyoxyalkylene ether, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyallyl ether, polyoxyethylene ether, Nonionic surfactants such as oxyalkylene amino ether, glycerin fatty acid ester, sorbitan fatty acid ester, fatty acid sodium, alkyl sulfate, polyoxyethylene sulfate, alkylbenzene sulfonate, α-olefin sulfonate, alkyl phosphate Anionic surfactants such as, amphoteric surfactants such as alkyldimethylamine oxide, alkylcarboxybetaine, alkylsulfobetaine, amide amino acid salts, succinic acid, citric acid, phosphoric acid, apple It may be used lactic acid, an organic acid or a salt or tartaric acid, pH adjusting agents, known chelating agents, antifoaming agents, colorants, additives such as perfumes.

In the synergistic fungicidal and antifungal composition of the present invention, (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and In addition to (C) benzoic acid and / or its alkali metal salt, it may contain one or more bactericidal / antibacterial agents, selected according to the field of application. Examples of such additional bactericidal / antibacterial agents are given below. However, bactericidal compositions containing other isothiazoline-based compounds, such as 5-chloro-2-methylisothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, which have drawbacks related to sensitization, are excluded.

Salicylic acid and salicylic acid salts, sorbic acid and its salts, dehydroacetic acid and its salts, propionic acid and its salts, silver compound, trichlorohydroxydiphenyl ether (triclosan), paraoxybenzoic acid ester and its sodium salt (methylparaben, propylparaben, butylparaben, Ethylparaben, isopropylparaben, benzylparaben), phenoxyethanol, phenol, sodium lauryldiaminoethylglycine, resorcin, zinc pyrithione (zinc pyrithione ZPT), isopropylmethylphenol, cetylpyridinium chloride, benzalkonium chloride, didecyldimethylammonium chloride (DDAC) Didecylmethyl polyoxyethylene ammonium propionate, didecylmethyl ammonium carbonate Bonates, quaternary ammonium salts such as benzethonium chloride, imidazole derivatives such as 1,10-di (3-decyl-2-methylimidazolium) decane dichloride, bisaminopropyldodecylamine, orthophenylphenol, orthophenylphenol sodium , Cresol, 1,3-dimethylol-5,5-dimethylhydantoin, alkylisoquinolinium bromide, thianthol, thymol, trichlorocarbanide, parachlorophenol, halocarban, hinokitiol, chlorhexidine hydrochloride, gluconesanchlorhexidine, chlorhexidine, Guanidine compounds such as polyaminopropyl biguanide (PHMB), polyaminopropylguanidine (PHMG), sodium sulfite, sodium bisulfite, Zyl alcohol, 2-bromo-2-nitropropane-1,3-diol (BRONOPOL), methyldibromonitrile glutaronitrile (1,2-dibromo-2,4-dicyanobutane), 5-bromo-5-nitro-1 , 3-dioxane), dichlorobenzyl chlorphenesin, phenoxyisopropanol and the like.

The synergistic antibacterial / antifungal composition of the present invention includes, for example, non-woven fabrics, textile products, paper towels, wet tissues, towels, wipes for wet wipes, and home and car fragrances and deodorants. , Used in toiletries such as liquid cleaning agents, antifouling agents and lotions, creams, soaps, etc., but the added amount is 0.002 in total active ingredient concentration for the above-mentioned applications of interest. It is preferable to add so as to be in the range of 0.5% to 1.5% by weight, more preferably about 0.005% to 1.0% by weight. As a method for addition, for example, a known method such as a dropping method, a coating method, a spraying method, or a dipping method can be used.

2-Methyl-4,5-trimethylene-4-isothiazolin-3-one (hereinafter abbreviated as MTI) can be produced by a known production method. 3-Iodo-2-propynyl-N-butylcarbamate (hereinafter abbreviated as IPBC) is commercially available from Lonza under the trade name Glycacil. Benzoic acid and sodium benzoate are commercially available as preservatives for food additives and as reagents.

When actually used, the synergistic antibacterial / antifungal composition of the present invention may be added to the object as a pre-mixed mixture, or the synergistic antibacterial / antifungal composition and the other composition May be added separately.

The present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to these examples.

The following examples illustrate (A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N in the synergistic fungicidal and antifungal composition of the present invention. -Elucidate the synergistic effect of the combination of butyl carbamate and / or (C) benzoic acid and / or its alkali metal salts. Moreover, the improvement of the antiseptic effect by the combination, the immediate effect on microorganisms and the antibacterial / antifungal effect will be clarified.

First, in order to perform MIC comparison of single preparations, the following preparations were obtained.
-MTI was used as it was to obtain a composition having an active ingredient concentration of 5%.
IPBC (Glycacil 2000, manufactured by Lonza) active ingredient 6% aqueous solution was used as it was.
-Benzoic acid (commercially available product) was dissolved in propylene glycol to obtain a composition of 5% aqueous solution of the active ingredient.
2-Methyl-4-isothiazolin-3-one (Zonen MT, active ingredient concentration 50%, manufactured by Chemiclear, hereinafter abbreviated as MIT)
Polyhexamethylene biguanide (Cosmocil CQ, active ingredient concentration 20%, manufactured by Arch Chemicals, hereinafter abbreviated as PHMB)
・ Polyhexamethylene guanidine (active ingredient concentration 20%, using commercial product, hereinafter abbreviated as PHMG)
・ 1,10-di (3-decyl-2-methylimidazolium) decane dichloride (effective component concentration 40%, manufactured by Arch Chemicals)

Preparation of fungus Pseudomonas aeruginosa NBRC 12589
Pseudomonas aeruginosa NBRC 13275
Staphylococcus aureus NBRC 12732
E. coli NBRC 3972
Candida albicans NBRC 1594
Aspergillus niger NBRC 6342
Penicillium citrinum NBRC 6352
The above bacteria, yeast, and mold were cultured in each nutrient medium. Bacteria were added to a normal bouillon liquid medium, yeast and mold were added to a malt liquid medium, and a bacterial solution and a spore suspension were prepared. The cell density of each bacterial solution and spore suspension was adjusted to 10 ⁶ cells / ml as a test solution.

(Test method)
Bacteria and spore suspensions adjusted to 10 ⁶ cells / ml are dispensed to a 96-well cell culture plate, and each preparation described above is added at the highest concentration of 2000 ppm to 8000 ppm, 8000 ppm to 12000 ppm, or 12000 ppm to 30000 ppm for evaluation. Add to pipette and mix by pipetting. After mixing, the same operation is repeated for columns 1 to 11 to mix, and column 12 is blank. A 96-well cell culture plate is cultured for 24 hours in a 36 ° C incubator for bacteria, 48 hours at 30 ° C for yeast, and 48 hours at 28 ° C for fungi. The minimum growth inhibitory concentration (hereinafter abbreviated as MIC) is 3 The average value was recorded.

(Evaluation criteria)
The MIC is measured by comparing the turbidity of the control sample and each preparation-added sample.

The evaluation results are shown below.

The following examples show synergistic effects in the preservative composition of the present invention.

Preparation of formulation example 1-4

(Formulation example 1)
Weigh 5.0 grams of 2-methyl-4,5-trimethylene-4-isothiazolin-3-one (hereinafter abbreviated as MTI), add 95.0 grams of purified water, stir and dissolve, and add 5.0% of MTI. Antiseptic preservative composition 1 was obtained.

(Formulation example 2)
IPBC (Glycacil L, manufactured by Lonza) was dissolved in dipropylene glycol to obtain a 5% aqueous preservative preservative composition.

(Formulation example 3)
IPBC (Glycacil L, manufactured by Lonza) was mixed and dissolved in dipropylene glycol and polyoxyethylene hydrogenated castor oil to obtain a 5% aqueous preservative preservative composition.

(Formulation example 4)
Benzoic acid (commercially available product) was dissolved in propylene glycol to obtain a preservative preservative composition having a 5% active ingredient aqueous solution.

The antiseptic preservative compositions 1, 2, 3, and 4 were used to measure the MIC values of the single agent and each mixed preparation to evaluate the synergistic effect.

Preparation of fungus Pseudomonas aeruginosa NBRC 12589
Candida albicans NBRC 1594
Aspergillus niger NBRC 6342
The above bacteria, yeast, and mold were cultured in each nutrient medium. Bacteria were added to a normal bouillon liquid medium, yeast and mold were added to a malt liquid medium, and a bacterial solution and a spore suspension were prepared. The cell density of each bacterial solution and spore suspension was adjusted to 10 ⁶ cells / ml as a test solution.

(Test method)
96-well cell culture plate in 10 ⁶ cells / ml bacterial solution was adjusted to, dispensed with a spore suspension minute, was added to each formulation before described is a maximum doping concentration 4000ppm ~ 24000ppm for evaluation, pipetting And mix. After mixing, the same operation is repeated for columns 1 to 11 to mix, and column 12 is blank. A 96-well cell culture plate is cultured for 24 hours in a 36 ° C incubator for bacteria, 48 hours at 30 ° C for yeast, and 48 hours at 28 ° C for mold, and the minimum inhibitory concentration (hereinafter abbreviated as MIC) is measured. did.

(Evaluation criteria)
As described in paragraph 0034, the MIC was measured by comparing the turbidity of the control sample and each preparation-added sample.

Tables 2 and 3 show MIC values for Pseudomonas aeruginosa NBRC 12589, Candida albicans NBRC 1594, Aspergillus niger NBRC 6342, and the mixing ratios of MTI, IPBC and benzoic acid for each single agent and each agent combination system. .

The FIC index (Fractional Inhibition Concentration Index) was calculated by the following equation (1).
FIC index = Qa / QA + Qb / QB (1)
(Where
Qa is the MIC value of the A component when the A component and the B component are used in combination.
QA is the MIC value of A component alone,
Qb is the MIC value of the B component when the A component and the B component are used together.
QB represents the MIC value of the B component alone)
The FIC index represents the effect of the combined use of the A component and the B component. When the FIC index is 1, it indicates that there is an additive action by the combined use of the A component and the B component. When the FIC index is greater than 1, it indicates that there is an antagonistic action by the combined use of the A component and the B component. When the FIC index is less than 1, it indicates that there is a synergistic effect by the combined use of the A component and the B component.

(Example A)
Table 2 shows the MIC value and FIC index for MTI, IPBC single agent and each mixing ratio.

(Example B)
Table 3 shows the MIC value and FIC index of MTI, benzoic acid single agent and each mixing ratio.

From Tables 2 and 3, the preservative composition of 2-methyl-4,5-trimethylene-4-isothiazolin-3-one (MTI) and 3-iodo-2-propynyl-N-butylcarbamate or benzoic acid is A synergistic effect can be expected compared to a preservative composition containing each single agent as an active ingredient.

(Bactericidal efficacy test)
Next, aqueous solutions having the compositions of Examples 1 to 12 and Comparative Examples 1 to 12 shown in Table 4 and Table 5 were prepared in order to compare the immediate effect of the sterilization / bactericidal effect against microorganisms in the single preparation and the mixed preparation. . The effects of these aqueous solutions were compared at 5 minutes, 1 hour, 3 hours, 6 hours, 24 hours and 48 hours for bacteria and 6 hours, 24 hours and 48 hours for molds.

(1) Test bacteria E. coli NBRC 3972 (E. coli)
・ Pseudomonas aeruginosa NBRC 12589 (Pseudomonas aeruginosa)
・ Staphylococcus aureus NBRC 12732 (Staphylococcus aureus)
・ Aspergillus niger NBRC 6342
・ Cladosporium cladosprioides NBRC 6348 (Cladosporium)

(2) Test medium NA medium: Ordinary agar medium [Eiken Chemical Co., Ltd.]
PDA medium: Potato dextrose agar medium [Eiken Chemical Co., Ltd.]
DIFCO: D / E neutralized liquid medium [BD, Becton Dickinson Company]

(3) Preparation of bacterial solution a) After culturing Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus in NA medium at 35 ° C. ± 1 ° C. for 24 hours, the cells of the obtained test bacteria are put into sterile phosphate buffered saline. What was suspended and adjusted so that the number of bacteria was about 10 ⁷ cells / mL and mixed in equal amounts was used as a test bacterial solution.
b) Aspergillus niger and Cladosporium were cultured in PDA medium at 27 ° C. ± 1 ° C. for 10 days, and the spores of the obtained test bacteria were suspended in physiological saline containing 0.05% polysorbate 80, and the number of spores Was mixed so as to be equal to about 10 ⁶ / mL, and the test bacterial solution was mixed.

(4) Sample preparation The aqueous solutions having the concentrations of Examples 1 to 12 and Comparative Examples 1 to 12 shown in Tables 4 and 5 were prepared using the following preparations *). Inoculate these aqueous solutions with 1% test bacterial solution, collect 1 ml every contact time, neutralize with 9 ml of D / E neutralized liquid medium, further dilute this diluted solution, For fungi, the number of viable bacteria is measured by agar plate mixing method using PDA medium. As a control, sterilized phosphate buffered saline was operated in the same manner. Bacteria were exposed for 5 minutes (immediately after inoculation) for 48 hours, and mold was viable for 0 minutes (immediately after inoculation) for 48 hours. A number measurement was made.
“* 1” MTI was used as it was to obtain a composition having an active ingredient concentration of 5%.
“* 2” IPBC (Glycacil, manufactured by Lonza) was dissolved in propylene glycol to obtain a composition of a 5% aqueous solution of the active ingredient.
"* 3" Benzoic acid (commercially available product) was dissolved in propylene glycol to obtain a composition of 5% active ingredient aqueous solution.
"* 4" MIT (Zonen MT, active ingredient concentration 50%, manufactured by Chemiclear)
"* 5" PHMB (Cosmocil CQ, active ingredient concentration 20%, used by Arch Chemicals)
"* 6" PHMG (active ingredient concentration 20%, using commercially available product)
“* 7” 1,10-di (3-decyl-2-methylimidazolium) decane dichloride (active ingredient concentration 40%, manufactured by Arch Chemicals)
"* 8" Didecyldimethylammonium chloride (Bardac 2240, manufactured by Lonza, using 40% active ingredient concentration, hereinafter abbreviated as DDAC)

The evaluation results of bacteria are shown below.

The mold evaluation results are shown below.

From Tables 4 and 5, Examples 1 to 12 have higher bactericidal efficacy and antibacterial properties in a shorter time than microorganisms such as bacteria and fungi compared to Comparative Examples 1 to 12.

(For anti-corrosion test for textile products and wet wipers)
In order to show the present invention more specifically, the following preservative efficacy test was performed in an actual application. The difference in the number of viable bacteria at the start to the viable count at the end was 5 Log or more for bacteria, and 4 Log for mold / yeast. When it was above, antimicrobial preservative efficacy was evaluated as (circle). Moreover, when it was 4 Log or more (bacteria) and 3 Log or more (mold / yeast), it was evaluated as △, and otherwise it was evaluated as ×.

(1) Test bacteria E. coli NBRC 3972 (E. coli)
・ Pseudomonas aeruginosa NBRC 12589 (Pseudomonas aeruginosa)
Staphylococcus aureus NBRC 12732 (Staphylococcus aureus)
・ Candida albicans NBRC1594 (Candida)
・ Aspergillus niger NBRC 6342
・ Cladosporium cladosprioides NBRC 6348 (Cladosporium)

(2) Test medium NA medium: Ordinary agar medium [Eiken Chemical Co., Ltd.]
PDA medium: Potato dextrose agar medium [Eiken Chemical Co., Ltd.]
SCDLP medium: SCDLP medium [Nippon Pharmaceutical Co., Ltd.]
GPLP medium: GPLP medium [Nippon Pharmaceutical Co., Ltd.]
SCDLPA medium: SCDLP agar medium [Nippon Pharmaceutical Co., Ltd.]
GPLPA medium: GPLP agar medium [Nippon Pharmaceutical Co., Ltd.]

(3) Preparation of bacterial solution a) After culturing Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus in NA medium at 35 ° C. ± 1 ° C. for 24 hours, the cells of the obtained test bacteria are put into sterile phosphate buffered saline. What was suspended and adjusted so that the number of bacteria was about 10 ⁸ cells / mL and mixed in equal amounts was used as a test bacterial solution.
b) 10 days for Aspergillus niger and Cladosporium (2 days for Candida), cultured in PDA medium at 27 ° C. ± 1 ° C., and then the spore of the obtained test bacterium was added with 0.05% polysorbate 80-added physiological saline A test bacterial solution was prepared by mixing an equal amount of the suspension prepared in such a manner that the number of spores was adjusted to about 10 ⁶ / mL.

(4) Preparation of sample The chemical solutions having the compositions of Examples 1 to 7 shown in Table 6 and Comparative Examples 1 to 6 shown in Table 7 were impregnated with 280 parts by weight of the chemical solution with respect to the weight of the fiber sheet base fabric. Stored for days.
After storage for 10 days, the fiber sheet was cut into a square having a side of about 6 cm, and four of these were stacked to prepare a sample. In addition, a fiber sheet base fabric not impregnated with a chemical solution was cut into a square of about 6 cm on a side, and four sheets of these were piled up, impregnated with a predetermined amount of sterilized purified water, and autoclaved (121 ° C., 15 minutes), did.

(5) Test operation Put the sample in a sterile petri dish, drop 0.2 mL of the bacterial solution, close the lid, and store the bacteria in an incubator at 37 ° C ± 1 ° C. After 7 days of storage, 20 mL of SCDLP liquid medium Place the sample in and mix for 1 minute to extract. The viable cell count of this extract was measured by culturing at 37 ° C. for 48 hours by the SCDLP agar medium pour method. For mold, after 7 days of storage, place the sample in 20 mL of GPLP liquid medium and mix and extract for 1 minute. The viable cell count of this extract was measured by culturing at 28 ° C. for 4 days by the GPLP agar medium pour method.

The evaluation results of the examples are shown below.

The evaluation results of the comparative examples are shown below.

From Table 6, Examples 1 to 7 have higher bactericidal efficacy and antibacterial antiseptic performance than Comparative Examples 1 to 6 in Table 7.

(Preservation efficacy test)
In order to compare the antiseptic efficacy in the actual system over a long period of time, an antiseptic efficacy test was conducted.

(1) Test bacteria E. coli NBRC 3972 (E. coli)
・ Pseudomonas aeruginosa NBRC 13275 (Pseudomonas aeruginosa)
Staphylococcus aureus NBRC 13276 (Staphylococcus aureus)
・ Candida albicans NBRC1594 (Candida)
-Aspergillus niger NBRC 9455 (Black mold)
・ Cladosporium cladosprioides NBRC 6348 (Cladosporium)

(2) Test medium NA medium: Ordinary agar medium [Eiken Chemical Co., Ltd.]
PDA medium: Potato dextrose agar medium [Eiken Chemical Co., Ltd.]
NB medium: Ordinary bouillon medium [Eiken Chemical Co., Ltd.]
SCDLPA medium: SCDLP agar medium [Nippon Pharmaceutical Co., Ltd.]
GPLPA medium: GPLP agar medium [Nippon Pharmaceutical Co., Ltd.]
DIFCO: D / E neutralized liquid medium [BD, Becton Dickinson Company]

(3) Preparation of bacterial solution a) After culturing Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus in NA medium at 35 ° C. ± 1 ° C. for 24 hours, the cells of the obtained test bacteria are put into sterile phosphate buffered saline. What was suspended and adjusted so that the number of bacteria was about 10 ⁸ cells / mL and mixed in equal amounts was used as a test bacterial solution.
b) 10 days for Aspergillus niger and Cladosporium, 2 days for Candida, and after culturing in PDA medium at 27 ° C ± 1 ° C, spore of the obtained test bacteria is suspended in physiological saline containing 0.05% polysorbate 80 An inoculation test bacterial solution was prepared by mixing the same turbidity and adjusting the spore count to about 10 ⁶ / mL.

Preservative-free lotion and lotion were used as samples for evaluation.
To the samples for evaluation, the addition amounts of Examples 1 to 8 and Comparative Examples 1 to 10 shown in Table 8 and Table 9 were added at respective active ingredient concentrations. Each sample was inoculated with 2% of the inoculum, and the bacteria were stored at 30 ° C incubator, and the mold and yeast were stored at 28 ° C. Collect 1 ml 7 days after inoculation, neutralize with 99 ml of D / E neutralized liquid medium, and further dilute this diluted solution using SCDLP medium for bacteria and GPLP medium for fungi. The number of viable bacteria was determined by the method of confirmation, and the remaining state of microorganisms was confirmed. This was repeated a total of 3 times (3 times inoculation) to compare the remaining state of the microorganisms.

Antiseptic test evaluation results

Antiseptic test evaluation results

From Table 8 and Table 9, Examples 1 to 8 have the effect of having high bactericidal efficacy, antibacterial properties and long-term antiseptic performance against microorganisms such as bacteria and molds / yeasts as compared with Comparative Examples 1 to 10. is doing.

Since the present invention is characterized by containing 2-methyl-4,5-trimethylene-4-isothiazolin-3-one as a bactericidal agent, it provides immediate effect and sterilization effect on microorganisms, and microbial contamination at a low concentration The present invention relates to a synergistic antibacterial and antifungal composition capable of remarkably avoiding spoilage caused by aging.

Claims

(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid and / or its alkali metal A synergistic antibacterial and antifungal composition characterized by containing a salt.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or an alkali metal salt thereof The synergistic antibacterial / antifungal composition according to claim 1, wherein the weight ratio (A) :( B) :( C) is 100 to 1: 1 to 50: 0.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or an alkali metal salt thereof The synergistic antibacterial / antifungal composition according to claim 1, wherein the weight ratio (A) :( B) :( C) is 100 to 1: 0 to 1 to 100.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or an alkali metal salt thereof 2. The synergistic antibacterial / antifungal composition according to claim 1, wherein the weight ratio (A) :( B) :( C) is 100 to 1: 1 to 50: 1 to 100.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or an alkali metal salt thereof 2. The synergistic antibacterial / antifungal composition according to claim 1, wherein the weight ratio (A) :( B) :( C) is 15 to 1: 1 to 10: 0.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or an alkali metal salt thereof The synergistic antibacterial / antifungal composition according to claim 1, wherein the weight ratio (A) :( B) :( C) is 15 to 1: 0 to 1 to 100.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, (B) 3-iodo-2-propynyl-N-butylcarbamate, (C) benzoic acid and / or an alkali metal salt thereof 2. The synergistic antibacterial / antifungal composition according to claim 1, wherein the weight ratio (A) :( B) :( C) is 15 to 1: 1 to 10: 1 to 100.
For non-woven fabrics, textile products, paper towels, wet tissues, hand wipes, wet wipes used for wipe sheets, household or car fragrances, deodorants, toilet liquid cleaners, antifouling agents or cosmetics. Item 8. A synergistic antibacterial / antifungal composition according to any one of Items 1 to 7.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid and / or its alkali metal The total of the active ingredients that are salt is non-woven fabrics, textile products, paper towels, wet tissues, towels, wet wipes used for wipes, wipes for households or cars, deodorants, liquid cleaners for toilets, The synergistic antibacterial / antifungal composition according to any one of claims 1 to 7, wherein the composition is contained in a stain or cosmetic at a ratio of 0.002% by weight or more and 1.5% by weight or less. .
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid and / or its alkali metal The total of the active ingredients that are salt is non-woven fabrics, textile products, paper towels, wet tissues, towels, wet wipes used for wipes, wipes for households or cars, deodorants, liquid cleaners for toilets, The synergistic antibacterial and antifungal composition according to any one of claims 1 to 7, which is blended in a soiling agent or cosmetic at a ratio of 0.005% by weight or more and 1.0% by weight or less. .
A wet wiper used for a nonwoven fabric, a textile product, a paper towel, a wet tissue, a towel, a wipe sheet, a household or a car containing the synergistic antibacterial / antifungal composition according to any one of claims 1 to 7 Fragrance, deodorant, toilet liquid cleaner, antifouling agent or cosmetic.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid and / or its alkali metal The nonwoven fabric, the textile product, the paper towel, the wet tissue, the towel, and the wipe sheet according to claim 11, wherein the total of the active ingredients that are salts is blended in a proportion of 0.002 wt% or more and 1.5 wt% or less. Wet wipers, home or car fragrances, deodorants, toilet liquid cleaners, antifouling agents or cosmetics.
(A) 2-methyl-4,5-trimethylene-4-isothiazolin-3-one and (B) 3-iodo-2-propynyl-N-butylcarbamate and / or (C) benzoic acid and / or its alkali metal The nonwoven fabric, the textile product, the paper towel, the wet tissue, the towel, and the wipe sheet according to claim 11, wherein the total amount of the active ingredients that are salts is 0.005% by weight or more and 1.0% by weight or less. Wet wipers, home or car fragrances, deodorants, toilet liquid cleaners, antifouling agents or cosmetics.
For the manufacture of non-woven fabrics, textile products, paper towels, wet tissues, hand wipes, wet wipes for wipes, wipes for household or car use, deodorants, toilet liquid cleaners, antifouling agents or cosmetics Use of the synergistic antibacterial and antifungal composition according to any one of claims 1 to 7.