JPH08183703A - Antibacterial and antifungal composition - Google Patents

Abstract

PURPOSE: To obtain an antibacterial and antifungal composition suitable for aqueous media and having little stimulation by using an enclosure compound prepared by enclosing 5-chloro-2-methyl-4-isothiazoline-3-one with a tetrakisphenol compound together with another specific antibacterial compound. CONSTITUTION: This antibacterial and antifungal composition comprises (A) a halogenated acetic acid ester compound combined with (B) an enclosure compound comprising a tetrakisphenol compound as a host component and 5- chloro-2-methyl-4-isothiazoline-3-one as a guest component and is suitable especially for aqueous media such as water in which rice has been washed. As a compound of the ingredient A, e.g. a compound of formula I (A is a 2-10C hydrocarbon; X is a halogen), especially bis(bromoacetoxy)ethane, bis(bromoacetoxy)propane, etc., are cited. As the tetrakisphenol compound of the ingredient B, e.g. a compound of formula II [R<1> to R<8> are each H, a halogen, an alkyl, an alkoxy or a phenyl; (n) is 0-3], e.g. 1,1,2,2-tetrakis(4-hydroxyphenyl) ethane, etc., are cited.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel antibacterial and antifungal composition, more specifically, it has little irritation to the skin and eyes, is chemically stable, and has a broad antibacterial spectrum. The present invention relates to an antibacterial / antifungal composition which has a long-lasting effect and is particularly suitable for an aqueous medium such as white water.

[0002]

2. Description of the Related Art Conventionally, water-based paints, paper coating liquids, and latexes prepared by using water systems for papermaking processes in the pulp and paper industry, water systems such as circulating cooling water in various industrial fields, or industrial water. In emulsions, starch slurries, printing pastes, leathers and the like, harmful microorganisms are easily propagated, which causes a decrease in productivity and quality.

Particularly, in the papermaking process of the pulp and paper industry, slime adheres to the wall surface of the place where the pulp slurry flows, chests, flow boxes, transportation pipes, etc., which are detached and mixed in the paper pulp products to be variously mixed. It causes unfavorable situations such as staining spots and stains on paper, contamination of paper and pulp products, paper breakage, and reduction of work efficiency, which is a major obstacle to the production of paper and pulp.

In order to prevent the damage caused by such microorganisms, treatment with a compound having an antibacterial action has hitherto been carried out, and as such an antibacterial agent, an isothiazolone compound alone has been used so far. Alternatively, those used in combination with other antibacterial agents are known (JP-A-62-70301, JP-A-3-18490, JP-B-6-21043).

However, the most commonly used isothiazolone compound, 5-chloro-2-
Methyl-4-isothiazolin-3-one is extremely irritating to the skin and eyes, requires careful handling, and is chemically unstable, so it requires a stabilizer. There is a drawback that the emulsion is broken by the inorganic salt added as an agent.

In order to improve such a defect, this 5
It has been attempted to include -chloro-2-methyl-4-isothiazolin-3-one with a bisphenol compound or the like (JP-A-1-190602, JP-A-5-4978). In technology,
It cannot always be said that the above drawbacks have been completely improved.

By the way, recently, due to the closure of industrial water, the neutralization of papermaking, or the increase of the mixing ratio of waste paper in the raw material for papermaking, the obstacles caused by filamentous fungi in addition to bacteria have been increasing. There has been a need for agents with strong antibacterial effects against microorganisms. Therefore, it has been attempted to combine two or more kinds of drugs and to broaden the antibacterial spectrum and enhance the antibacterial activity by their synergistic effect. For example, a combination of 5-chloro-2-methyl-4-isothiazolin-3-one or a metal salt thereof with another antibacterial agent (Japanese Patent Publication No. 58-4682, Japanese Patent Publication No. 60-5428).
1, JP-A-60-84203, JP-A-60-84203
No. 139601, Japanese Unexamined Patent Publication No. 6210003, and Japanese Unexamined Patent Publication No. 2-53703), 5-chloro-2-methyl-4-isothiazoline-3- Irritating about on,
Instability has not been improved.

Further, 1,1,6,6-tetrakis (2,
4-dimethylphenyl) -2,4-hexadiyne-1,
Using 5-diol as a host component, 5-chloro-2-
A combination of an inclusion compound containing methyl-4-isothiazolin-3-one as a guest component and a halogenated nitroalcohol has been proposed (JP-A-3-271204), but it is formulated into a stable form. I don't know about that.

[0009]

DISCLOSURE OF THE INVENTION The present invention solves various drawbacks of the antibacterial and antifungal agent containing 5-chloro-2-methyl-4-isothiazolin-3-one as a component and solves the problems of the skin. It has low irritation to eyes and eyes, is chemically stable, does not cause emulsion destruction, has a broad antibacterial spectrum, has high antibacterial activity, and has a long-lasting effect, especially in aqueous media. The purpose of the present invention is to provide a fungicidal and antifungal composition suitable for use.

[0010]

DISCLOSURE OF THE INVENTION The inventors of the present invention have conducted extensive studies to develop a fungicidal and antifungal agent having the above-mentioned preferable properties, and as a result, 5-chloro-2-methyl-4-isothiazoline-3. The present invention was completed based on this finding that a composition containing an inclusion compound of 1-one with a tetrakisphenol compound and a specific compound having other antibacterial activity can meet the purpose. Came to.

That is, the present invention uses (a) at least one halogenated acetic acid ester compound and (b) a tetrakisphenol compound as host components, and 5-chloro-2
Disclosed is a fungicidal and antifungal composition, which comprises a combination of inclusion compounds containing -methyl-4-isothiazolin-3-one as a guest component.

The composition of the present invention must contain a combination of the component (a) and the component (b) as an active ingredient, and the component (a) is, for example, a compound represented by the general formula:

Embedded image (A in the formula is a saturated or unsaturated hydrocarbon group having 2 to 10 carbon atoms, and X is a halogen atom). Especially preferred among these are bis (bromoacetoxy) ethane, bis (bromoacetoxy) propane and bis (bromoacetoxy) butene.

Next, the component (b) of the composition of the present invention is 5-
It is an inclusion compound containing chloro-2-methyl-4-isothiazolin-3-one as a guest component and a tetrakisphenol compound as a host component.

Embedded image The compound represented by

In the general formula (II), R ¹ to R ⁸ are each a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a phenyl group with or without a substituent. Here, examples of the halogen atom include a fluorine atom, chlorine atom and bromine atom, and examples of the lower alkyl group include a methyl group, an ethyl group and n.
-Propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group and the like, and lower alkoxy groups include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n -
Butoxy group, isobutoxy group, sec-butoxy group, t
An ert-butoxy group and the like can be mentioned. On the other hand, examples of the phenyl group with or without a substituent include a phenyl group, a tolyl group, a xylyl group, and a halogenophenyl group. Further, R ¹ to R ⁸ may be the same or different from each other. Furthermore, n is 0 or an integer of 1 to 3.

Examples of such tetrakisphenol compounds include 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane and 1,1,2,2-tetrakis (3-methyl-4-hydroxyphenyl). Ethane 1,
1,2,2-tetrakis (3-bromo-4-hydroxyphenyl) ethane, 1,1,2,2-tetrakis (3,3
5-dimethyl-4-hydroxyphenyl) ethane, 1,
1,2,2-tetrakis (3-t-butyl-4-hydroxyphenyl) ethane, 1,1,2,2-tetrakis (3-chloro-4-hydroxyphenyl) ethane, 1,
1,2,2-tetrakis (3,5-dichloro-4-hydroxyphenyl) ethane, 1,1,2,2-tetrakis (3-fluoro-4-hydroxyphenyl) ethane,
1,1,2,2-tetrakis (3,5-difluoro-4
-Hydroxyphenyl) ethane, 1,1,2,2-tetrakis (3-methoxy-4-hydroxyphenyl) ethane, 1,1,2,2-tetrakis (3,5-dimethoxy-4-hydroxyphenyl) ethane, 1,1,2,2-
Tetrakis (3-chloro-5-methyl-4-hydroxyphenyl) ethane, 1,1,2,2-tetrakis (3-
Chloro-5-phenyl-4-hydroxyphenyl) ethane, 1,1,2,2-tetrakis (3-phenyl-4-
Hydroxyphenyl) ethane, 1,1-bis (4-hydroxyphenyl) -2,2-bis (3-methyl-4-hydroxyphenyl) ethane, 1,1,3,3-tetrakis (4-hydroxyphenyl) propane , 1, 1, 3,
3-tetrakis (3-methyl-4-hydroxyphenyl) propane, 1,1,3,3-tetrakis (3-chloro-4-hydroxyphenyl) propane, 1,1,4
4-tetrakis (4-hydroxyphenyl) butane,
1,1,4,4-tetrakis (3-methyl-hydroxyphenyl) butane, 1,1,4,4-tetrakis (3-
And chloro-4-hydroxyphenyl) butane.

The inclusion compound containing the tetrakisphenol compound as a host component and 5-chloro-2-methyl-4-isothiazolin-3-one as a guest component can be prepared by a known method, for example, water, methanol, ethanol, etc. At least one tetrakisphenol compound as the host component is dissolved or suspended in the lower alcohol, acetone, or an aqueous medium containing these compounds, and then 5-chloro-2-methyl-4- It is prepared by adding isothiazolin-3-one and stirring the mixture at a temperature of usually 0 to 100 ° C., preferably 10 to 50 ° C. for about 10 minutes to 24 hours, preferably for about 30 minutes to 10 hours. be able to.

5-Chloro-2-methyl-4-isothiazolin-3-one is usually prepared by chlorinating β-thioketoamide in an inert organic ester solvent such as acetic acid ester, or β-substituted thiocyanoacrylamide. Is treated with acid to obtain isothiazolone, which is then chlorinated. In this case, the antibacterial activity is 5-chloro-
About 1/1 of 2-methyl-4-isothiazolin-3-one
2-methyl-4-isothiazolin-3-one, which is only 0, is produced as a by-product. However, in the present invention, such a 2
The one containing -methyl-4-isothiazolin-3-one may be used as it is. In this case, 5-chloro-2-methyl-4-isothiazolin-3-one is selectively the guest component, and 2-methyl-4-isothiazolin-3-one is incorporated in a very small amount. Depending on the type, it will be less than 1 mol% of 5-chloro-2-methyl-4-isothiazolin-3-one. In addition, commercially available 5-chloro-2-methyl-4-isothiazolin-3-one (for example, trade name: Caisson WT, manufactured by Rohm & Haas) has a by-product 2-methyl-4- Magnesium chloride and magnesium nitrate are contained as stabilizers in addition to isothiazolin-3-one, but in the present invention, such a mixture can also be used as the guest component of the component (b).

The inclusion compound containing the tetrakisphenol compound thus formed as a host component and 5-chloro-2-methyl-4-isothiazolin-3-one as a guest component is usually in a solid state. The clathrate compound is obtained in a powder form by taking it out from the reaction completion liquid by a known means such as filtration, and drying it by vacuum drying or the like. 5-chloro-2-methyl-4 in this clathrate
The content of -isothiazolin-3-one varies depending on the type of the tetrakisphenol compound as the host component, the reaction temperature, the reaction time, etc., but is usually about 1 to 2 mol per mol of the tetrakisphenol compound.

The composition of the present invention can be prepared by mixing the component (a) and the component (b) in a solid state with a crushing / mixing mixer. The halogenated acetic acid ester of the component (a) can be prepared. When the compound is produced, it is taken out by dissolving it in a solvent in order to prevent solidification in the tank, and it is commercially available as it is. Therefore, (b) component is added to this solution, and a dispersant and other additives are added if necessary. Advantageously, the agent is added and milling and mixing are carried out. In this way, particle size 1
It is possible to obtain a suspension in which the inclusion compound of 00 μm or less, preferably 5 μm or less, is dispersed in a stable state.

Since the composition of the present invention is often used by being mixed with an aqueous liquid, it is preferable to formulate the composition in a state of being suspended in an aqueous medium, but if desired, a flowable agent, a wettable powder,
It can also be formulated in the form of a solid agent, a suspoemulsion in which both solid and liquid are present, or an aqueous solution.

In this case, the formulation components include a diluent, an excipient, a binder, a lubricant, a surfactant, an antifoaming agent, depending on the purpose.
A pH adjuster, a metal corrosion inhibitor, a thickener, a freezing point depressant, etc. are used. As the wettable powder, in addition to the active ingredient, clay, bentonite, fine mineral powders such as diatomaceous earth, starch, organic substances such as urea, and inorganic salts such as sodium sulfate are used as carriers, mixed with surfactants, etc. Prepare by dry grinding.

For flowable and suspoemulsions, in addition to active ingredients, surfactants and defoamers are mixed with a dispersion medium, finely pulverized and emulsified, and thickeners, stabilizers, freezing point depressants, specific gravity regulators, etc. Is added and mixed to prepare. As the dispersion medium, water is preferable, but a non-aqueous medium such as oil can also be used unless the inclusion body is dissolved.In particular, in the case of a water-insoluble active ingredient such as a brominated antibacterial and antifungal agent, it is not emulsified. This is preferable because it can be completed.

As the solid agent, active ingredients, excipients, binders, lubricants and the like are added, mixed, tableted, extruded and granulated, and a suspension containing an inclusion body is prepared and sprayed. It can be prepared by drying.

Surfactants used in flowables and wettable powders may be those generally used as wetting agents and dispersants. In the anionic system, alkylsulfates, dialkylsulfosuccinates, and naphthalenesulfonates are condensed with formalin. Substances, lignin sulfonates, polycarboxylates and the like. Examples of the nonionic type include polyoxyethylene alkyl ether, polyoxyethylene alkylaryl ether, and polyoxyethylene polyoxypropylene block copolymer. Examples of the suspension stabilizer include sodium polyacrylate, carboxymethyl cellulose, polyvinyl alcohol, guar gum, xanthan gum, sodium montmorillonite, silica and the like.

Examples of the pH adjusting agent include acids such as sulfuric acid, phosphoric acid, citric acid, maleic acid and succinic acid, and salts thereof. When water is used as the dispersion medium, examples of the freezing point depressant include hydrophilic solvents such as ethylene glycol, propylene glycol and glycerin. The defoaming agent is added mainly to prevent foaming during wet pulverization, and a silicone-based defoaming agent is useful. When the dispersion medium is water, the specific gravity adjusting agent may be a soluble compound such as urea.

Component (a) and component (b) in the composition of the present invention
The ratio to the components is usually 5-chloro-2- in the inclusion compound.
The weight ratio of methyl-4-isothiazolin-3-one to halogenated acetic acid ester compound is 1: 100 to 10
It is chosen to be in the range 0: 1, preferably 1:10 to 10: 1. Further, the concentration of the clathrate compound in the suspension is practically about 1 to 50% by weight, but 1 to 15% by weight is particularly preferable.

The composition of the present invention comprises (a) a halogenated acetic acid compound and (b) a tetrakisphenol compound as host components and 5-chloro-2-methyl-4-isothiazolin-3-one as a guest component. The compounds are preferably formulated in a form dispersed in an aqueous liquid using a dispersant.

As the dispersant in this case, for example, alkyl sulfate, dialkyl sulfosuccinate, formalin condensate of naphthalene sulfonate, lignin sulfonate,
Examples thereof include anionic surfactants such as polycarboxylic acid salts, nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene alkylaryl ethers, and polyoxyethylene polyoxypropylene block copolymers. Of these, formalin condensates of naphthalene sulfonate and lignin sulfonate are particularly preferable. This dispersant is used in such a proportion that the weight ratio of the clathrate compound to the dispersant is in the range of 1:10 to 10: 1, preferably 1: 5 to 5: 1.

Further, various additives used as required include, for example, suspension stabilizers, pH regulators, freezing point depressants, defoamers, and specific gravity regulators.

Examples of the suspension stabilizer include carboxymethyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, guar gum,
Xanthan gum, rhamsan gum, sodium polyacrylate, polyacrylamide, alkyl methacrylate /
Diethylaminoethylmethacrylate copolymer, alkylmethacrylate / N-vinyl-2-pyrrolidoneacrylate copolymer, alkylmethacrylate / polyethyleneglycolmethacrylate copolymer, dodecylfumarate / diethylaminoethylmethacrylate copolymer,
Examples thereof include styrene / maleic acid copolymer, sodium montmorillonite, and silica. Examples of the pH adjusting agent include acids such as sulfuric acid, phosphoric acid, citric acid, maleic acid and succinic acid, and salts thereof, and freezing point depressants include
For example, hydrophilic solvents such as ethylene glycol, propylene glycol, and glycerin, defoaming agents such as silicone-based ones, and specific gravity adjusting agents include soluble compounds such as urea.

Regarding the amount of the antibacterial and antifungal agent composition of the present invention to be used, in the case of water used in the fields such as the pulp and paper industry, the amount of the active ingredient is 0.1 to 100 ppm, and In the case of coating liquids, starch slurries, latex emulsions, etc., the amount of active ingredient is 1 to 50.
It is effective to add it so as to be 0 ppm.

[0032]

The antibacterial and antifungal composition of the present invention comprises a combination of an inclusion compound containing 5-chloro-2-methyl-4-isothiazolin-3-one as a guest component and a halogenated acetic acid ester compound. When it is contained in an aqueous dispersion, it is easy to mix and is stable when used in an object containing an aqueous medium such as white water, and the inclusion compound produces 5-chloro-2-methyl. -4-Isothiazolin-3-one is gradually released, and due to the synergistic effect of this and halogenated acetic acid ester compounds, it exhibits a broad antibacterial spectrum and excellent antibacterial activity, and also has excellent sustainability of these effects. ing. In addition, the composition of the present invention is irritating and unstable 5-chloro-2-methyl-4-isothiazoline-
Since 3-one is clathrated, it is less irritating to the skin and eyes and is chemically stable.

The antibacterial and antifungal composition of the present invention has the above-mentioned characteristics and is used as a slime control agent in the field of paper and pulp industry, or as an aqueous paint, a paper coating solution, a latex emulsion and a starch. slurry,
It is suitable for use as an agent for preventing microbial damage in printing paste and leather.

[0034]

EXAMPLES The present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Reference Example Production of Inclusion Compound In 1,5 ml of water, 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane (1.1355 g, 2.85)
Millimolar) and stirred for 30 minutes at 25 ° C. to disperse, and then caisson WT (trade name, manufactured by Rohm & Haas) 20 g (5-chloro-2-methyl-4-isothiazolin-3-one as 11 (0.4 mmol) was gradually added, and the mixture was stirred at 25 ° C. for 3 hours for reaction. Next, the precipitate was suction filtered and vacuum dried at room temperature to obtain a clathrate compound as a pale yellow powder. The guest / host molar ratio in this clathrate was 1.16 for 5-chloro-2-methyl-4-isothiazolin-3-one and 0.02 for 2-methyl-4-isothiazolin-3-one.

Example 1 6.0 parts by weight of the clathrate compound obtained in Reference Example, 5.0 parts by weight of sodium formalin naphthalenesulfonate as a dispersant, 1.0 part by weight of xanthan gum and water.
After premixing with 82.0 parts by weight and uniformly dispersing, 5.0 parts by weight of 1,2-bis (bromoacetoxy) propane and 1.0 part by weight of a silicone-based defoaming agent were added to this, and the mixture was stirred at room temperature. A slurry-type antibacterial and antifungal agent was prepared by pulverizing at high speed for 1 hour using a sand grinder under normal pressure. The particle size of the clathrate compound was 1 μm or less.

Example 2 In place of 1,2-bis (bromoacetoxy) propane in Example 1, 1,4-bis (bromoacetoxy)-
An aqueous suspension of the antibacterial / antifungal agent was prepared in the same manner as in Example 1 using 5.0 parts by weight of 2-butene.

Example 3 In the same manner as in Example 1, except that 5.0 parts by weight of 1,2-bis (bromoacetoxy) ethane was used in place of 1,2-bis (bromoacetoxy) propane in Example 1, bacteriostatic treatment was carried out. An aqueous suspension of fungicide was prepared.

Comparative Example 1 1,2-bis (bromoacetoxy) propane 5.0 parts by weight was added to diethylene glycol monomethyl ether 9
It was dissolved in 5.0 parts by weight to prepare an antibacterial and antifungal agent.

Comparative Example 2 1,4-bis (bromoacetoxy) -2-butene 5.
0 parts by weight of diethylene glycol monomethyl ether
It was dissolved in 95.0 parts by weight to prepare an antibacterial and antifungal agent.

Comparative Example 3 5.0 parts by weight of 1,2-bis (bromoacetoxy) ethane was dissolved in diethylene glycol monomethyl ether to prepare an antibacterial / antifungal agent.

Test Examples The following tests were conducted on the antibacterial and antifungal agents obtained in Examples and Comparative Examples. (1) Suppression test: Pseudomonas aeruginosa (P
a), Aerobacterium aerogenes (Aa), Bacillus subtilis (Bs), Aspergillus niger (A)
n), mold of Geotricum (G), and unidentified pink slime bacterium (P) are suspended in physiological saline and divided into test tubes in equal amounts, and Waxman's medium is added.
A predetermined amount of the above-mentioned drug was added to this, and the mixture was cultured at 32 ° C with shaking. After 24 hours, the growth inhibitory concentration was judged from the degree of reproduction of microorganisms according to the following criteria. Addition when there are signs of reproduction when the microorganisms are actively growing, when there is obvious reproduction, when there is a sign of reproduction, when there is no sign of reproduction, and when there are signs of reproduction. The drug concentration was defined as the inhibitory concentration. The results are shown in Table 1.

(2) Sterilization test: Pseudomonas aeruginosa (Pa), Aerobactor aerogenes (A)
a), Bacillus subtilis (Bs), Aspergillus niger (An), fungus (G) of the genus Geotricum, and unidentified pink slime bacterium (P) are suspended in physiological saline, and test tubes are suspended in equal volumes. Then, a prescribed amount of the above-mentioned drug was added thereto, and the mixture was shaken and contacted. After contacting for a predetermined time, it was diluted with sterilized water, Waxman's medium was added, and after 48 hours, the concentration of the added drug at which the number of microbial colonies became 10 or less per ml was defined as the bactericidal concentration. The results are shown in Table 1.

[0044]

[Table 1]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI technical indication location A01N 37:12 31:08) (72) Inventor Hiroshi Dosomoto 4-11 Ginza, Chuo-ku, Tokyo No. 2 In Somar Corporation (72) Inventor Koji Kawai 4-11-2 Ginza 4-chome, Chuo-ku, Tokyo Inside Somar Corporation

Claims (3)

[Claims] 1. (a) At least one halogenated acetic acid ester compound and (b) a tetrakisphenol compound as a host component, and 5-chloro-2-methyl-4-isothiazolin-3-one as a guest component. A fungicidal and fungicide composition comprising a combination of clathrate compounds. 2. 5-chloro-2-methyl-4-isothiazoline-3 containing (a) a halogenated acetic acid ester compound and (b) a tetrakisphenol compound as host components.
The antibacterial and fungicide composition according to claim 1, wherein the clathrate compound containing -one as a guest component is dispersed in an aqueous liquid using a dispersant. 3. The antibacterial agent according to claim 1 or 2, wherein the halogenated acetic acid ester compound is at least one selected from bis (bromoacetoxy) ethane, bis (bromoacetoxy) propane and bis (bromoacetoxy) butene. Antifungal composition.