JP4052488B2 - Fungicide - Google Patents

Description

【００４６】
この結果から、コレステロールによって包接化されたＯＩＴは、包接化されていないＯＩＴと同等の抗菌力を有することがわかる。
塗料からの溶出試験
水性リシン塗料各１００ｇに、実施例１のＯＩＴのコレステロール包接化合物および比較例１のＯＩＴを、ＯＩＴが塗料中に０．１５重量％含有されるようにそれぞれ配合した。
【００４７】
次に、ＪＩＳ Ｚ ２９１１（１９９２）に準じ、３ｃｍ×３ｃｍの濾紙に、調製された各塗料を約０．５ｇ塗布して１日乾燥後、１００ｍｌの水中に入れて３日間振とうした。その後、水中のＯＩＴを液体クロマトグラフィーで定量し、水中に溶出したＯＩＴの溶出率を求めた。
その結果、溶出率はＯＩＴの全量に対して、実施例１では、３０重量％、比較例１では、８０重量％であった。このことより、コレステロールによって包接化されたＯＩＴは、水によって溶出しにくいことがわかる。
【図面の簡単な説明】
【図１】実施例１の赤外吸収スペクトルである。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a bactericidal agent, and more particularly, to a bactericidal agent having good handleability and useful for outdoor paints or outdoor adhesives.
[0002]
[Prior art]
Conventional paper mills, various industrial water such as cooling water circulation process, metal processing oil such as cutting oil, casein, starch paste, glue, paper coating liquid, surface sizing agent, paint, adhesive, synthetic rubber latex In various industrial products such as printing inks and cement admixtures, harmful microorganisms are easy to propagate, which causes a decrease in productivity and quality and generation of malodor. Therefore, many disinfectants are used for the control and sterilization of the propagation of these microorganisms.
[0003]
An isothiazolone compound is known as one of the agents that suppress or control the generation of harmful microorganisms in these industrial products.
This isothiazolone compound exhibits excellent efficacy in antifungal, antiseptic, algal and yeast prevention, and is widely used as an industrial disinfectant in the above-described fields.
[0004]
[Problems to be solved by the invention]
However, since an isothiazolone compound has strong skin irritation, it is difficult to handle as it is, and handling properties and workability are not so good.
In addition, since the solubility in water is relatively high, even if a paint or adhesive containing a bactericide containing an isothiazolone compound is applied to an outdoor building, the isothiazolone compound is eluted and washed away by rainwater. There is a problem that the effect cannot be sustained.
[0005]
Therefore, the present invention has been made in view of such circumstances, and provides a bactericidal agent that has good handleability and workability, and is less likely to elute into water and can maintain its effect well outdoors. The purpose is to do.
[0006]
[Means for Solving the Problems]
In order to achieve the above object, the fungicide of the present invention contains 2-n-octyl-4-isothiazolin-3-one and cholesterol, and the 2-n-octyl-4-isothiazolin-3-one is It is characterized in that it is the clathrate by the cholesterol.
[0012]
Also, the disinfectant can be suitably used for outdoor paints or outdoor adhesive.
[0013]
DETAILED DESCRIPTION OF THE INVENTION
[0028]
In the present invention, cholesterol is a kind of steroid whose molecular formula is represented by C ₂₇ H ₄₆ O, and the fungicide of the present invention is 2-n-octyl-4-isothiazolin-3-one (OIT) , It contains cholesterol. The proportion of OIT and cholesterol blended is, for example, preferably in the range of 0.5 to 6, more preferably 1 to 3 in terms of mole ratio of cholesterol to OIT .
[0029]
Further, in the above formulation, OIT is Ru clathrated by cholesterol. Such cholesterol clathrate OIT can be easily obtained by dissolving and mixing with the OIT and cholesterol and an appropriate solvent. At this time, inclusion can be promoted by adding about 1% by weight or less of water to the solvent. Moreover, as a specific preparation method, for example, a known method such as a direct method of a saturated solution method, a solvent method, a spray drying method of a drying method, or a freeze drying method can be used. Preferably, for example, a solvent method is used.
[0030]
The solvent method includes, for example, a concentration method and a precipitation method. In the concentration method, for example, OIT and cholesterol are mixed in an amount of 1 to 1000 times, preferably 10 to 500 times by weight, with respect to cholesterol in the above-described blending ratio. In addition, the OIT is included by cholesterol by stirring and mixing at 5 to 80 ° C., preferably 15 to 60 ° C. for 0.5 to 24 hours, preferably 1 to 10 hours. Next, the solution is removed by evaporation, and the remaining cholesterol inclusion compound of OIT is washed with a solvent that acts as a poor solvent for the inclusion compound, such as water or methanol, and after filtration, Drying such as reduced pressure drying at 10 to 60 ° C., preferably 20 to 50 ° C. for 1 to 48 hours, yields white crystals of OIT cholesterol inclusion compound.
[0031]
In addition, in the precipitation method, for example, OIT and cholesterol are added in a solvent of 1 to 1000 times by weight, preferably 10 to 500 times by weight, preferably 5 to 80 ° C. Is included by stirring and mixing at 15 to 60 ° C. for 0.5 to 24 hours, preferably 1 to 10 hours, so that OIT is included in cholesterol. The solution is then cooled to 10 ° C. or lower, preferably 5 ° C. or lower to precipitate the cholesterol inclusion compound of OIT , and after filtration, 10 to 60 ° C., preferably 20 to 50 ° C. for 1 to 48 hours. Drying such as drying under reduced pressure is performed to obtain white crystals of the cholesterol inclusion compound of OIT .
[0032]
The solvent used at this time is not particularly limited as long as it dissolves OIT and does not inhibit inclusion, and examples thereof include water such as methanol, ethanol, n-propanol, iso-propanol, n- Alcohol solvents such as butanol and tert-butanol, such as ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, 1,4-butanediol, 1,5-pentanediol, ethylene Glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, tripropylene Glycol solvents such as lenglycol monomethyl ether, for example, ketone solvents such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, for example, ether solvents such as dioxane, tetrahydrofuran, and ethyl ether, such as ethyl acetate, butyl acetate, and isobutyl acetate Ester solvents such as aromatic solvents such as benzene, toluene, xylene, methylnaphthalene and solvent naphtha, halogenated hydrocarbon solvents such as carbon tetrachloride, chloroform and methylene chloride, such as dimethylformamide and dimethyl Examples include polar solvents such as sulfoxide and acetonitrile. These solvents may be used alone or in combination of two or more. Among these solvents, in the concentration method, for example, ketone solvents, ester solvents and halogenated hydrocarbon solvents are preferable, and for example, acetone, ethyl acetate, carbon tetrachloride, chloroform and methylene chloride are more preferable. In the precipitation method, for example, an alcohol solvent is preferable, and for example, methanol is more preferable.
[0033]
The thus obtained bactericidal agent of the present invention is formulated into known dosage forms such as liquids (including water suspensions and oils), pastes, powders, granules, etc., depending on the purpose of use. Can be used. Preferably, a liquid agent is mentioned, for example. In order to formulate as a liquid agent, the cholesterol inclusion compound of OIT may be appropriately dissolved in a solvent. As the solvent used at this time, for example, the solvent used for obtaining the above-mentioned cholesterol inclusion compound of OIT can be used, preferably, for example, a glycol solvent, more preferably, for example, ethylene. Glycol, diethylene glycol, propylene glycol, dipropylene glycol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether are used. In particular, the cholesterol inclusion compound of OIT is preferably formulated as a water suspension. For example, the formulation of OIT cholesterol inclusion compound is 1 to 70% by weight based on the preparation obtained. However, it is preferable that the content is 5 to 50% by weight, and the suspension is stirred and suspended.
[0034]
Furthermore, the disinfectant of the present invention may contain known additives such as other disinfectants, surfactants, antioxidants and the like for the purpose of use.
Other fungicides include, for example, organic iodine compounds such as 3-iodo-2-propynyl-butyl-carbamate, diiodomethyl-p-toluylsulfone and p-chlorophenyl-3-iodopropargyl formal, such as 4,5 Dithiol-based compounds such as dichloro-1,2-dithiol-3-one, for example, thiophene-based compounds such as 3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide, such as tetramethylthiuram disulfide Thiocarbamate compounds such as 2,4,5,6-tetrachloroisophthalonitrile and the like nitrile compounds such as N- (fluorodichloromethylthio) -phthalimide and N- (fluorodichloromethylthio) -N, N'-dimethyl-N-phenyl-sulfur Haloalkylthio compounds such as rufamide, for example, pyridiline compounds such as 2,3,5,6-tetrachloro-4- (methylsulfonyl) pyridine, for example pyrithione compounds such as zinc pyrithione and sodium pyrithione, for example 2- Benzothiazole compounds such as (4-thiocyanomethylthio) benzothiazole, for example, triazine compounds such as 2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine, such as methyl-2- Examples thereof include imidazole compounds such as benzimidazole carbamate and 2- (4-thiazolyl) -benzimidazole. These fungicides may be used alone or in combination of two or more. Moreover, although these compounding ratios change with the dosage forms and the intended purpose, it is preferable to contain about 0.1 to 80 weight% in a liquid agent and about 10 to 99.9 weight% in a powder agent, for example.
[0035]
Examples of the surfactant include known surfactants such as soaps, nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, and polymer surfactants. Preferably, a nonionic surfactant and an anionic surfactant are mentioned.
Examples of the nonionic surfactant include polyoxyalkylene aryl phenyl ether, polyoxyethylene nonyl phenyl ether, and a block copolymer of ethylene oxide and propylene oxide.
[0036]
Examples of the anionic surfactant include alkylbenzenesulfonic acid metal salts, alkylnaphthalenesulfonic acid metal salts, polycarboxylic acid type surfactants, dialkylsulfosuccinic acid ester metal salts, and polyoxyethylene distyrenated phenyl ether sulfate ammonium salts. And lignin sulfonic acid metal salts. Examples of these metal salts include sodium salts, potassium salts, and magnesium salts.
[0037]
Examples of the antioxidant include phenolic antioxidants such as 2,6-di-tert-butyl-4-methylphenol and 2,2′-methylenebis [4-methyl-6-tert-butylphenol], Examples thereof include amine-based antioxidants such as alkyldiphenylamine and N, N′-di-s-butyl-p-phenylenediamine. For example, in the case of a liquid agent, these surfactant and antioxidant are added in an amount of 0.1 to 5 parts by weight with respect to 100 parts by weight of the liquid agent.
[0038]
The bactericidal agent of the present invention thus obtained has weak skin irritation and good handling and workability. For example, for slime control of industrial water such as paper pulp mills and cooling water circulation processes, sterilization washing, etc. Can be used as well as anti-mold in metal processing oil such as cutting oil, casein, starch paste, glue, paper coating liquid, surface sizing agent, paint, adhesive, synthetic rubber latex, printing ink, cement admixture, etc. It can be applied to antiseptic, algae and yeast prevention, and can be effectively used as an industrial disinfectant. In addition, since the solubility in water is relatively low, even if it is incorporated in outdoor paints and adhesives and applied to outdoor buildings, OIT , which is an active ingredient, is less likely to be eluted by rainwater, resulting in good effects as a bactericidal agent. Can last.
[0039]
In addition, although the addition amount of the fungicide of the present invention may be appropriately determined according to the application target, it acts as an active ingredient concentration of about 0.005 to 20%, preferably about 0.01 to 5%. Is preferred.
[0040]
【The invention's effect】
As described above, the disinfectant of the present invention is weak in skin irritation, has good handleability and workability, and has a relatively low solubility in water. Even if it is constructed, the OIT which is an active ingredient is hardly eluted by rainwater, and the effect as a bactericide can be favorably sustained.
[0041]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples.
Example 1
Cholesterol 2.0 g , OI T0 . To 37 g , 30 ml of chloroform was added and stirred at room temperature for 2 hours. Next, the solvent was removed by evaporation, washed with 50 ml of methanol, and dried under reduced pressure at 40 ° C. for 24 hours to obtain 2.0 g of OIT cholesterol clathrate compound powder (white crystals) (yield 84%). The powder was quantified by liquid chromatography to determine the OIT content. The content of OIT was 14.0% by weight.
[0042]
Further, in order to confirm inclusion, powder X-ray analysis and infrared absorption spectrum were measured, and solubility was examined. The solubility was determined by adding 1 g of powder to 20 ml of water, giving 200 shakes per minute for 2 hours, filtering through a membrane filter, and quantifying the filtrate by liquid chromatography.
Infrared absorption spectrum is shown in FIG. 1, and powder X-ray data and solubility are shown below.
Powder X-ray data: Interplanar spacing (Å) 23.860 (I / Io; 100), 16.980 (I / Io; 47), 6.267 (I / Io; 47), 5.771 (I / Io) 57), 5.260 (I / Io; 47)
Solubility: 78ppm
Example 2
100 g of methanol was added to 2.0 g of cholesterol and 0.37 g of OIT, and dissolved at 50 ° C. Then, it stirred at room temperature for 2 hours, and also stirred at 5 degreeC for 2 hours. The resulting precipitate was filtered with suction, and then dried under reduced pressure at 40 ° C. for 24 hours to obtain 1.5 g of OIT cholesterol clathrate powder (white crystals) (yield 63%). The powder was quantified by liquid chromatography to determine the OIT content. The content of OIT was 14.8% by weight.
[0043]
Moreover, in order to confirm inclusion, solubility was investigated by the same operation as Example 1. The results are shown below.
Solubility: 104ppm
Comparative Example 1
As a comparative example, a propylene glycol solution of OIT (OIT content of about 45% by weight) was prepared. In addition, the solubility by the same operation as Example 1 was as follows.
Solubility: 627ppm
Antibacterial activity measurement Bacterium was cultured at 33 ° C for 18 hours, mold and yeast were cultured at 28 ° C for 3 days by glucose dilution agar culture (1000-2.0 µg / ml, 10-step dilution), and minimal growth inhibition The concentration (MIC, μg / ml) was determined.
[0044]
Samples were prepared using the OIT cholesterol inclusion compound of Example 1 and the OIT of Comparative Example 1 so that the OIT was 8% by weight.
The test bacteria are as follows.
No.1: Bacillus subtilis (Bacillus subtilis, Bacillus subtilis, Gram-positive bacteria)
No.2: Staphylococcus aureus (Staphylococcus aureus, Staphylococcus aureus, Gram-positive bacteria)
No.3: Escheriachia coli (Escherichia coli, Gram-negative bacteria)
No.4: Pseudomonas aeruginosa (Pseudomonas aeruginosa, Pseudomonas aeruginosa, Gram-negative bacteria)
No.5: Serratia marcescens (Serratia marcescens)
No.6: Aspergillus niger (black mold)
No.7: Penicillium citrinum (blue mold)
No.8: Cladosporium cladosporioides
No.9: Mucor spinescens (Mucor spinescens)
No.10: Rhodotorula rubra (red yeast)
No.11: Saccharomyces cerevisiae (white yeast)
The antibacterial activity against these bacteria was as shown in Table 1 at the minimum growth inhibitory concentration (MIC, μg / ml).
[0045]
[Table 1]

[0046]
From this result, it can be seen that OIT clathrated with cholesterol has an antibacterial activity equivalent to that of non-inclusion OIT.
Elution test from paint Each 100 g of aqueous lysine paint was blended with the cholesterol inclusion compound of OIT of Example 1 and OIT of Comparative Example 1 so that OIT was contained in the paint at 0.15% by weight.
[0047]
Next, according to JIS Z 2911 (1992), about 0.5 g of each prepared paint was applied to a filter paper of 3 cm × 3 cm, dried for 1 day, placed in 100 ml of water and shaken for 3 days. Thereafter, OIT in water was quantified by liquid chromatography, and the elution rate of OIT eluted in water was determined.
As a result, the elution rate was 30% by weight in Example 1 and 80% by weight in Comparative Example 1 with respect to the total amount of OIT. From this, it can be seen that OIT encapsulated by cholesterol is difficult to elute with water.
[Brief description of the drawings]
1 is an infrared absorption spectrum of Example 1. FIG.

Claims (2)

Bactericidal , comprising 2-n -octyl-4-isothiazolin-3-one and cholesterol , wherein the 2-n-octyl-4-isothiazolin-3-one is included by the cholesterol Agent. The disinfectant according to claim 1, which is used for an outdoor paint or an outdoor adhesive.

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