Classifications

• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
  • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
  • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
  • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
  • A01N47/12—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, neither directly attached to a ring nor the nitrogen atom being a member of a heterocyclic ring

Definitions

• 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.
• 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.
• 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.
• isothiazolin-3-one a compound having a high antiseptic effect has been used for general industrial purposes since ancient times.
• 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.
• 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, ⁇ -chlorobenzaldoxime, ⁇ -chloro).
• Patent Document 3 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
• Patent Document 5 International Patent Application PCT / EP1999 / 006056
• 2-methyl-4-isothiazolin-3-one and 3-iodo-2-propynyl-N-butylcarbamate.
• a combined synergistic bactericidal composition is disclosed.
• Patent Document 6 Japanese Patent Laid-Open No. 10-219282
• Patent Document 7 Japanese Patent 2981451
• a single preparation lacks long-term effects, lacks efficacy, or easily causes the emergence of resistant bacteria.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• (B) 3-iodo-2-propynyl-N-butyl carbamate is included in an inclusion compound such as cyclodextrin ( ⁇ -form, ⁇ -form, ⁇ -form). You may use what has been.
• 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.
• 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, ⁇ -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
• 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
• (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.
• 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 benzeth
• 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.
• a known method such as a dropping method, a coating method, a spraying method, or a dipping method can be used.
• MTI 2-Methyl-4,5-trimethylene-4-isothiazolin-3-one
• MTI 2-Methyl-4,5-trimethylene-4-isothiazolin-3-one
• IPBC 3-Iodo-2-propynyl-N-butylcarbamate
• Glycacil trade name Glycacil
• Benzoic acid and sodium benzoate are commercially available as preservatives for food additives and as reagents.
• 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.
• 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
• PHMG 1,10-di (3-decyl-2-methylimidazolium) decane dichloride
• 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.
• MIC minimum growth inhibitory concentration
• the MIC is measured by comparing the turbidity of the control sample and each preparation-added sample.
• Formulation example 2 IPBC (Glycacil L, manufactured by Lonza) was dissolved in dipropylene glycol to obtain a 5% aqueous preservative preservative composition.
• 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.
• 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.
• 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.
• the FIC index 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.
• Table 2 shows the MIC value and FIC index for MTI, IPBC single agent and each mixing ratio.
• 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.
• MTI 2-methyl-4,5-trimethylene-4-isothiazolin-3-one
• 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.
• 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
• 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]
• test bacteria 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.
• 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.
• 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.
• 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)
• 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.]
• 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.
• 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.
• Examples 1 to 7 have higher bactericidal efficacy and antibacterial antiseptic performance than Comparative Examples 1 to 6 in Table 7.
• 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
• 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]
• Preservative-free lotion and lotion were used as 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.
• 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.
• 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.

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• Life Sciences & Earth Sciences (AREA)
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• Detergent Compositions (AREA)
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• 2015
  • 2015-02-06 WO PCT/JP2015/053351 patent/WO2015122364A1/ja active Application Filing
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