JPH0234350B2 - HOSETSUKAGOBUTSUOYOBISOREOGANJUSURUSATSUKINZAI - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a cyclodextrin clathrate compound of 2-n-octyl-4-isothiazolin-3-one,
and a bactericide containing the same as an active ingredient. 2-n-octyl-4-isothiazoline-3-
OIT (hereinafter sometimes abbreviated as OIT) is a compound useful as a non-medical bactericidal and algaecide (Japanese Patent Publication No. 46-21240). However, since OIT is an oily substance at room temperature and is immiscible with water, it is difficult to prepare an aqueous formulation, and it is difficult to prepare a solid formulation (e.g., powder, wettable powder, granules, etc.). It is also difficult to find something satisfying. Conventionally, the preparation of aqueous formulations of oily substances requires the use of very large amounts of surfactants, and such formulations have not been used because they have an adverse effect on the target product or material. In addition, solidification of oily substances can be achieved by adsorption to binders such as starch, lactose, gelatin, dextrin, gum arabic, albumin, cellulose derivatives, synthetic polymers, silicic anhydride, calcium citrate, synthetic aluminum silicate, magnesium oxide, etc. However, the solid products obtained by these methods had drawbacks such as oozing of oily substances and not being able to withstand long-term storage. As a result of extensive research in order to improve these drawbacks, the present inventor found that OIT forms a novel clathrate compound with cyclodextrin that has not been described in any literature, and that by using the clathrate compound, it is possible to easily prepare aqueous preparations ( Furthermore, even when solidified, oily substances do not ooze out, and because of its sustained release properties, the effect is more durable than that of OIT, and OIT's original sterilizing effect is superior to that of OIT. It was discovered that skin irritation was significantly reduced without impairing the effect, and the present invention was completed based on these findings. That is, the present invention relates to a bactericide characterized by containing (1) a cyclodextrin clathrate compound of OIT, and (2) a cyclodextrin clathrate compound of OIT as an active ingredient. The cyclodextrin used in the present invention is a cyclic dextrin obtained by allowing cyclodextrin glycosyl transferase to act on starch or a hydrolyzate of starch. Specifically, there are three types of glucopyranose groups: α-cyclodextrin in which 6 glucopyranose groups are bonded through α-1,4-glucosidic bonds, β-cyclodextrin in which 7 glucopyranose groups are bonded, and γ-cyclodextrin in which 8 glucopyranose groups are bonded. In this case, any one type or a mixture of two or more of these cyclodextrins is used. OIT Cyclodextrin Inclusion Compound OIT
It can be produced by reacting cyclodextrin with cyclodextrin in a solvent. For example, cyclodextrin is suspended or dissolved in an appropriate amount of water, an alcohol such as methanol or ethanol, or a water-containing organic solvent such as acetone, and OIT is added to this as is, or an alcohol or glycol-based organic solvent (e.g. After adding a solution dissolved in propylene glycol, diethylene glycol, etc., and stirring and mixing for several hours, the precipitate that is formed is washed separately with, for example, acetone, and the uninclusion is removed.
OIT can be separated and dried to obtain an OIT clathrate compound as a powder. In addition, the above-mentioned uninclusive OIT
The bactericidal stock solution of the present invention can also be prepared in the form of a reaction solution mixed with the following. The clathrate compound of the present invention thus obtained contains approximately 11.2 (±1.5)% OIT, and in some cases OIT that does not form a cyclodextrin and clathrate compound coexists. It is within the scope of the invention. The OIT cyclodextrin clathrate of the present invention can be applied as a disinfectant, or can be dispersed in a suitable carrier or mixed with a suitable solid carrier, and optionally further added with a dispersing agent, a suspending agent, etc. , spreading agent, penetrating agent, wetting agent, mucilage agent,
By adding stabilizers etc., for example, oil agent,
It may be used in dosage forms such as emulsions, wettable powders, powders, granules, fine granules, tablets, pastes, suspensions, and sprays, and may also be used as other fungicides, insecticides, deterioration inhibitors, etc. It can be used in the same way as known disinfectants. The liquid carrier used in the preparation of the disinfectant of the present invention may be any liquid as long as it does not react with the active ingredient, such as water, alcohols (e.g. methyl alcohol, ethyl alcohol, glycol,
(e.g., ethylene glycol, glycerin, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.),
Ethers (e.g. dioxane, tetrahydrofuran, cellosolve, etc.), aliphatic hydrocarbons (e.g.
hexane, liquid paraffin, gasoline, kerosene, kerosene, fuel oil, machine oil, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.) and other halogenated hydrocarbons (e.g. , chloroform, carbon tetrachloride, etc.), acid amides (e.g., dimethylformamide, etc.), esters (e.g., ethyl acetate, butyl acetate, fatty acid glycerin ester, etc.), or nitriles (e.g., acetonitrile, etc.) alone. It can be used alone or as a mixture of two or more. In addition, examples of solid carriers include starch, dextrin, clays (e.g., kaolin, bentonite, acid clay, etc.),
Examples include talc (e.g., talc powder, waxite powder, etc.), silicas (e.g., diatomaceous earth, silicic anhydride, mica powder, etc.), alumina, sulfur powder, activated carbon, calcium carbonate, gum arabic, etc. It may be used or a mixture of two or more types may be used. In addition, in producing the fungicide of the present invention, for example, emulsifiers, dispersants, suspending agents, vegetable oils,
Mineral oil, higher alcohol, surfactant, thickener,
Flow aids, antioxidants, etc. may be added as appropriate. Examples of emulsifiers and dispersants used include soaps, sulfate esters of higher alcohols,
Surfactants such as alkylsulfonic acids, alkylarylsulfonic acids, quaternary ammonium salts, fatty acid esters, polyalkylene oxides, or anhydrosorbitols are used, and these surfactants are generally used per part by weight of the active ingredient. hand
It is preferable to use 0.02 to 0.3 parts by weight, or to contain it in an amount of about 5 to 80% of the total amount of the preparation. Also,
For example, alginic acid, agar,
CMC, polyvinyl alcohol, vegetable oil, bentonite, cresol soap, etc. can also be used. Furthermore, other types of fungicides (for example, organophosphate fungicides, benzimidazole fungicides, organic sulfur fungicides, phenolic fungicides, antibiotics, etc.), insecticides (natural insecticides, carbamate insecticides, organophosphate insecticides, etc.)
Perfumes, low-molecular or high-molecular phosphates, and the like may be mixed as appropriate. In particular, for example 2-benzimidazolecarbamate methyl ester, 2-
(4-thiazolyl)-benzimidazole, tetrachloroisophthalonitrile, 1,2-benzisothiazolin-3-one, (2-N-methylbenzamide) disulfide, 8-hydroxyquinoline copper, etc. as a mixed preparation. is advantageous. The content of the active ingredient (cyclodextrin clathrate compound of OIT) in the fungicide of the present invention in the above dosage form varies depending on the dosage form and purpose of use, but is generally about 5 to 100%. For example, in the case of a solution, it is appropriate to have a concentration of about 5
~20%, approximately 10 to 80% for wettable powders, approximately 10 to 100% for powders, approximately 10 to 60 for suspensions
It is preferable to set it to about %. In addition, during actual use, depending on the purpose of use, appropriate solvents, diluents, fillers, etc. may be added to these dosage forms of disinfectants, or the amount of these disinfectants added to the substance to be applied may be adjusted. It is preferable to adjust the concentration of the active ingredient to about 0.005 to 0.1%, preferably 0.01 to 0.05%. The fungicide of the present invention can be applied to general industrial products such as paints, wood and bamboo products, leather, textiles, proteins, wall covering materials,
It is applied to industrial products made of all organic materials such as glue, adhesives, tents, hoses, waterproof cloth, waxes, coated paper, textile aids, and resin emulsions, and effectively prevents quality deterioration caused by bacteria and mold. The application method depends on the object, purpose, etc.
For example, the method may be appropriately selected from coating methods, spraying methods, dipping methods, mixing methods, kneading methods, and the like. Generally, it is preferable to apply the fungicide of the present invention to the target water-containing product so that the final concentration of the active ingredient is about 50 to 1000 ppm. More specifically, when added to paints, for example, water-soluble polymeric compounds such as casein and formalin copolymers, water-soluble vinyl and acrylic polymers, water-soluble vegetable oils and polyester resins, or, for example, acrylic For paints based on latexes such as methyl styrene, vinyl acetate-styrene, vinyl acetate-methyl methacrylate, vinyl acetate-maleic anhydride, styrene-butadiene, vinyl acetate-methyl acrylate, and vinyl chloride-vinyl acetate. It is preferable to add the fungicide of the present invention so that the final concentration of the active ingredient is about 100 to 500 ppm. In addition, when adding it to spinning oil, for example, mix mineral oil, higher alcohol, etc. with vegetable oil such as olive oil, castor oil, peanut oil, etc., and add a nonionic or anionic surfactant as necessary, so that it is evenly distributed. The fungicide of the present invention is preferably added to the mixed spinning oil so that the final concentration of the active ingredient is about 50 to 200 ppm. In this case, intermittent addition is also effective, and if necessary, it may be used alternately or in combination with other fungicides. The disinfectant of the present invention is useful in the industry because it has no risk of residual toxicity or pollution, does not have any adverse effects on target water-containing products, and can easily, inexpensively, and accurately exhibit excellent antiseptic and antifungal effects. Gender is extremely important. Hereinafter, the present invention will be explained in more detail with reference to Examples and Test Examples, but the scope of the present invention is not limited by these in any way. Example 1 1 part by weight of β-cyclodextrin (Celdex N, manufactured by Nippon Gosei Kagaku Kogyo) was uniformly suspended in 10 parts by weight of water, 0.2 part by weight of OIT was added, and the mixture was stirred and mixed at room temperature for 4 hours. After centrifugation (3000 rpm, 15 minutes), the precipitate was filtered under reduced pressure to remove moisture, washed three times with 10 parts by weight of acetone, and dried to obtain an OIT clathrate compound as a powder. The OIT content in the product is
It was 11.2%. Example 2 α-, β-, γ-mixed cyclodextrin (α26%, β11%, γ8%, other dextrins 55
%, Toyoderin Ρ, manufactured by Toyo Jozo Co., Ltd.) was uniformly suspended in 76 g of water, 10.5 g of a propylene glycol solution of OIT (OIT content 47.6%) was added dropwise, and the mixture was stirred and mixed at room temperature for 4 hours. 2g of Kao Atlas), Celogen WS as a thickener
Add 1.5 g of -C (manufactured by Daiichi Kogyo Seiyaku) to prepare a product (suspension agent). When using, use it as is or dilute it with water to the specified concentration. Example 3 20 g of OIT clathrate compound produced in Example 1, 75 g of clay, and 3 ml of sodium dibutylnaphthalene sulfonate
% and 2% of sodium ligninsulfonate are mixed and ground to form a product (wettable powder). When using, use it as is or dilute it with water to the specified concentration. Example 4 10 g of Toyoderin Ρ (manufactured by Toyo Jozo Co., Ltd.) was suspended in 71.0 g of water, and a propylene glycol solution of OIT (OIT
After dropping 10.5 g of 2-benzimidazole carbamic acid methyl ester (content 47.6%) and stirring at room temperature for 4 hours, Demol N was added as a dispersant.
(manufactured by Kao Atlas) and 1.5 g of Celogen WS-C (manufactured by Daiichi Kogyo Seiyaku) as a thickener were added and atomized to obtain a product (suspension agent). When using,
Either as is or diluted with water to the specified concentration. Example 5 To 20 g of the OIT clathrate compound produced in Example 1, 2
-(4-thiazolyl)-benzimidazole 10g,
A product (wettable powder) is prepared by mixing and pulverizing 65 g of clay, 3% sodium dibutylnaphthalene sulfonate, and 2% sodium lignin sulfonate. When using,
Either as is or diluted with water to the specified concentration. Example 6 25 g of tetrachloroisophthalonitrile and 35 g of clay were added to 40 g of the OIT clathrate compound produced in Example 1 and mixed with stirring to obtain a product (powder). When using, use it as is or dilute it with water to the specified concentration. Example 7 To 30 g of the OIT clathrate compound produced in Example 1,
1. Add 10 g of 2-benzisothiazolin-3-one and 60 g of clay and mix with stirring to obtain a product (powder). When using, use it as is or dilute it with water to the specified concentration. Example 8 To 20 g of the OIT clathrate compound produced in Example 1,
(2-N-methylbenzamide) disulfide 10
g, 65 g of clay, 3% sodium dibutylnaphthalene sulfonate, and 2% sodium lignin sulfonate are mixed and ground to obtain a product (wettable powder). When using, use it as is or dilute it with water to the specified concentration. Example 9 8-
8 g of hydroxyquinoline copper, 2 g of Demol N (manufactured by Kao Atlas Co., Ltd.), and 1% of Celogen WS-C (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) are added and mixed and atomized to obtain a product (suspension agent). When using, use it as is or dilute it with water to the specified concentration. Test Example Antifungal effect of the fungicide of the present invention on emulsion paints Regarding a propylene glycol solution having the same OIT content as the suspension prepared in Example 2,
The anti-mold effects on paints were compared according to the JIS standard (Z-2911) paint mold resistance test method. The test results are shown in the table. Two types of paints were used: a vinyl acetate emulsion paint (Vini Paint manufactured by Kansai Paint Co., Ltd.) and an acrylic emulsion paint (Viny Deluxe No. 100 manufactured by Kansai Paint Co., Ltd.).
The results indicate the degree of mold growth on the sample surface as follows: -, +,
The mold resistance is indicated in four stages, and the indications (1, 2, 3) according to the JIS standard mold resistance indication method are also listed. −: No mold growth observed on the sample surface. +: Mold growth is observed on approximately 1/3 or less of the sample surface. : Mold growth is observed on approximately 1/3 or more of the sample surface. : Mold growth is observed on the entire surface of the sample. 【table】

[Brief explanation of drawings]

Figure 1 shows the clathrate compound obtained in Example 1 of copper.
A powder X-ray diffraction diagram measured with Ka-ray is shown. Horizontal line 2θ
represents the diffraction angle, and the vertical line represents the diffraction intensity.

Claims (1)

[Claims] 1 2-n-octyl-4-isothiazoline-3
-one cyclodextrin clathrate. 2 2-n-octyl-4-isothiazoline-3
A bactericide characterized by containing a cyclodextrin clathrate compound of -1 as an active ingredient.