JPH0692806A - Stable liquid antibacterial and antifungal formulation - Google Patents

Abstract

(57) [Abstract] [Objective] The present invention provides an isothiazolone derivative and
It is an object of the present invention to provide a stable liquid antibacterial and antifungal preparation by preventing decomposition of these in a liquid preparation containing benzisothiazolin-3-one at the same time. [Structure] Compound A (Wherein, X represents a hydrogen atom or a halogen atom, and Y represents a lower alkyl group) and an isothiazolone derivative or a complex compound thereof, and a compound B 1,2-benzisothiazolin-3-one or a salt thereof represented by (In the formula, R ₁ , R ₂ and R ₃ may be the same or different and each is a hydrogen atom, a halogen atom, an alkyl group, a hydroxyl group, a cyano group, a thiol group, a nitro group, a carboxyl group, an amino group or a sulfone group. A stable liquid antibacterial and antifungal preparation, characterized by comprising a propanol derivative represented by the formula (1).

Description

Detailed Description of the Invention

[0001]

[Object of the Invention]

FIELD OF THE INVENTION The present invention relates to a liquid preparation containing an isothiazolone derivative and 1,2-benzisothiazolin-3-one, both of which are used as industrial antibacterial and antifungal agents, at the same time. The present invention relates to providing a liquid antibacterial and antifungal preparation in which a fungal component is stabilized over time.

[0002]

2. Description of the Related Art An aqueous solution preparation containing an isothiazolone derivative as an active ingredient decomposes the active ingredient in a short period of time to cause precipitation.
Not practical.

Therefore, some studies have been made on the formulation of a bactericidal and antifungal agent containing an isothiazolone derivative as an active ingredient or its stabilization.

For example, a preparation in which an isothiazolone derivative is dissolved in an amide compound (JP-A-2-22978,
JP-A-2-229179), in a solvent of diols such as ethylene glycol, at least one isothiazolone derivative as an active ingredient and 2-hydroxymethyl-2-
A preparation in which nitro-1,3-propanediol is dissolved (Japanese Patent Laid-Open No. 56-99401) is known.

However, the decomposition of compound B caused by the combined use of the isothiazolone derivative (compound A) and 1,2-benzisothiazolin-3-one (compound B) is prevented, and it is possible to prevent the decomposition of compound A and compound B during long-term storage.
No stable liquid antibacterial / antifungal formulation containing a seed component is known.

[0006]

[Problems to be Solved by the Invention] Industrial fungicidal and antifungal agents include industrial raw materials such as bacteria, filamentous fungi, and yeasts.
Paints, adhesives, pastes, pigments, leather, papermaking, oils, wood,
It is necessary that building interior materials, etc. do not deteriorate over a long period of time. Therefore, it is desired to have a broad antibacterial spectrum, a smaller dosage, and a strong antibacterial and antifungal effect. Therefore, a combination of two or more of various antibacterial and antifungal components has been studied so far.

However, as described above, the isothiazolone derivative and 1,2-benzisothiazoline-3-
Liquid formulations containing on are not always stable enough,
The combination has not been fully studied.

Under such circumstances, the object of the present invention is to provide a liquid antibacterial and antifungal preparation which contains an isothiazolone derivative and 1,2-benzisothiazolin-3-one at the same time and is stable for a long period of time. To do.

[0009]

[Constitution of the invention]

DISCLOSURE OF THE INVENTION In order to develop a new liquid antibacterial and antifungal agent which meets the above-mentioned needs, the present inventors have subjected a wide range of compounds to various tests and examined their stability.

As a result, as described below, in the liquid preparation containing the compound A and the compound B at the same time as the active ingredient having bactericidal and fungicidal activity, the compound C was blended and coexisted to give a stable liquid preparation. The present invention has been completed and the present invention has been completed.

That is, the gist of the present invention is that

Compound A

[Chemical 4] (In the formula, X represents a hydrogen atom or a halogen atom, and Y represents a lower alkyl group.), Or an isothiazolone derivative or a complex compound thereof,

Compound B

[Chemical 5] 1,2-benzisothiazolin-3-one or a salt thereof represented by

Compound C

[Chemical 6]

(In the formula, R ₁ , R ₂ and R ₃ may be the same or different and each is a hydrogen atom, a halogen atom, an alkyl group, a hydroxyl group, a cyano group, a thiol group, a nitro group, a carboxyl group or an amino group. Alternatively, a stable liquid antibacterial and antifungal preparation, characterized in that it is made to coexist with a propanol derivative represented by a sulfone group.

Preferred representative examples of the compound A which can be used in the present invention are 2-methyl-5-chloro-1,2-methyl-isothiazolin-3-one and 2-methyl-1,
2-isothiazolin-3-one or a complex compound thereof, for example, zinc chloride, zinc bromide, zinc iodide, zinc sulfate, zinc acetate, copper chloride, nickel chloride, calcium chloride, magnesium chloride, iron chloride, manganese chloride, Examples of the complex compound include sodium chloride, barium chloride, ammonium chloride, and other amine chlorides.

The salt of compound B is preferably an alkali metal salt such as sodium or potassium, or an ammonium salt.

Specific examples of the compound C include, for example, n-propanol, isopropanol, 2-amino-2-methylpropanol, 3-amino-2-methylpropanol, 2-bromo-3-chloropropanol, 3
-Bromo-2-chloropropanol, 3-bromo-2,
2-Dimethylpropanol, 2-bromo-2-nitropropanediol, 2-nitropropanol, 2,2-dinitropropanol, 3-mercapto-2-methylpropanol and the like can be mentioned, and particularly n-propanol, isopropanol, 2-bromo. 2-Nitropropanediol is preferred.

In the compound A, X is a halogen atom and Y is a lower alkyl group, such as 2-
Methyl-5-chloro-isothiazolin-3-one is usually obtained and used as a mixture together with its by-product, 2-methyl-isothiazolin-3-one, and each may be used after isolation. In the invention, it can be used as a mixture thereof.

In the present invention, the mixing ratio of the compound A and the compound B is 10: 1 to 1:10, preferably 5: 1 to 1: 5 by weight, and these mixtures are added to a liquid preparation in an amount of 0. The amount may be 1 to 20% by weight, preferably 0.1 to 15% by weight.

The addition ratio of the compound C is 0.1 to 90.
%, Preferably 1.0-40% by weight.

[0022]

In the present invention, compound C stabilizes two kinds of fungicidal and fungicidal components, compound A and compound B, without degrading with time in a liquid preparation using water or / and an organic solvent as a solvent. Have an effect.

[0023]

EXAMPLE The antibacterial and antifungal preparation of the present invention can be obtained by the following method. That is, compound C is added to compound A and compound B which are two kinds of antibacterial and fungicidal components of the present invention, or compound A and compound B are added to compound C and various solvents as exemplified below are added. In addition to dissolve,
The liquid preparation of the present invention can be obtained by adding a surfactant and, if necessary, other auxiliary agents to this and mixing them uniformly.

The type of the solvent is not particularly limited as long as it can dissolve or disperse the compound A and the compound B. For example,

Water, alcohols Methyl alcohol, ethyl alcohol, ethylene glycol, benzyl alcohol, etc.

Aromatic hydrocarbons benzene, toluene, xylene, ethylbenzene, chlorobenzene, cumene, methylnaphthalene, etc.

Halogenated hydrocarbons: chloroform, carbon tetrachloride, dichloromethane, chloroethylene, trichlorofluoromethane, dichlorodifluoromethane, etc.

Ethers Ethyl ether, ethylene oxide, dioxane, tetrahydrofuran, etc.

Ketones Acetone, methyl ethyl ketone, cyclohexanone, methyl isobutyl ketone, etc.

Esters Ethyl acetate, butyl acetate, ethylene glycol acetate, amyl acetate, etc.

Nitriles Acetonitrile, propionitrile, acrylonitrile, etc.

Sulfoxides Dimethyl sulfoxide, etc.

Alcohol ethers Ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, etc.

Amines Ethylamine, dimethylamine, triethylamine, isobutylamine, etc.

Aliphatic or alicyclic hydrocarbons n-hexane, cyclohexane, etc.

Industrial gasoline (petroleum ether, solvent naphtha, etc.) and petroleum fractions (paraffins, kerosene,
Examples include light oil.

In formulating, a surfactant is used for the purpose of emulsification, dispersion, wetting, foaming and spreading. Examples of such a surfactant include those shown below, but the surfactants are not limited to these examples.

Nonionic polyoxyethylene alkyl ether, polyoxyethylene alkyl ester, polyoxyethylene sorbitan alkyl ester, sorbitan alkyl ester, etc.

Anionic alkylbenzene sulfonate, alkyl sulfosuccinate, dialkyl sulphosuccinate, alkyl sulphate, polyoxyethylene alkyl sulphate, aryl sulphonate, etc.

Cation alkylamine salt (laurylamine, stearyltrimethylammonium chloride, alkyldimethylbenzylammonium chloride, etc.)

Amphoteric carboxylic acid (betaine) sulfate ester, etc.

In addition to these, polyvinyl alcohol (PVA), carboxymethyl cellulose (CM
Various auxiliary agents such as C), gum arabic, polyvinyl acetate, gelatin, casein, sodium alginate, etc. can be used.

Further, the antibacterial and antifungal preparation of the present invention exhibits a sufficient antifungal effect by the mixture of the compound A and the compound B, but if necessary, a general antibacterial and antifungal agent such as 2- (4-thiazolyl) benzimidazole, parachlorometaxylenol, parachlorometacresol,
2,3,5,6-tetrachloro-4- (methylsulfonyl) pyridine, N-dichlorofluoromethyl-N ′,
N'-dimethyl-N-sulfamide, 2,4,5,6-
Tetrachloroisophthalonitrile, 3-iodo-2-propargyl butylcarbamate, 2-bromo-2-bromomethylglutanitrile (1,2-dibromo-2,4-dicyanobutane), diiodomethyl-p-tolylsulfone, dodecyl One or more of guanidine hydrochloride and the like can be used in combination.

The present invention will be described below with reference to examples.

[0045]

Examples 1 to 4 The compositions shown in Tables 1 and 2 were uniformly mixed to obtain the antibacterial and antifungal agents of Examples 1 to 4 and Comparative Examples 1 and 2.

The numbers in Tables 1 and 2 indicate the blending ratio (% by weight) of each composition.

[0047]

[Table 1]

[0048]

[Table 2]

Next, the effect of the practice of the present invention will be proved by a test example. Test example Formulation stability (precipitation presence / absence) test 5 formulations of the examples and comparative examples shown in Tables 1 and 2 above were used.
Put 300 ml into a 00 ml glass bottle, 55 ℃
It was allowed to stand in a thermostatic chamber and room temperature, and its stability was evaluated according to the following criteria. The results are shown in Tables 3 and 4.

In addition, the stability was examined in the same manner as above, except that the compounds C of Examples 1 and 2 were replaced with those shown in Table 5, and the others were formulated as in Examples 1 and 2.
The results are shown in Table 5.

Criteria ++: Precipitation is clearly visible at the bottom of the glass bottle +: Precipitation is slightly visible at the bottom of the glass bottle −: No precipitation is observed

[0052]

[Table 3] Stability of formulation at 55 ° C

[0053]

[Table 4] Stability of formulation at room temperature

[0054]

[Table 5] Stability after 3 months

[0055]

In the liquid antibacterial and antifungal preparation of the present invention,
By making the compound C coexist, it is possible to prevent decomposition of the isothiazolone derivative compounds A and B, which had been decomposed to form a precipitate, and to stabilize for a long time.

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[Procedure amendment]

[Submission date] September 10, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0016

[Correction method] Change

[Correction content]

[0016] Preferred examples of the compounds A which can be used in the present invention, 2-methyl-5-chloro-1,2 - isothiazolin-3-one and 2-methyl-1,2-isothiazolin-3-one, or their Complex compounds of, for example, zinc chloride, zinc bromide, zinc iodide, zinc sulfate, zinc acetate, copper chloride, nickel chloride, calcium chloride, magnesium chloride, iron chloride, manganese chloride, sodium chloride,
Examples thereof include complex compounds of barium chloride, ammonium chloride, and other amine chlorides.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0019

[Correction method] Change

[Correction content]

In the compound A, X is a halogen atom and Y is a lower alkyl group, such as 2-
Methyl-5-chloro- 1,2- isothiazolin-3-one is usually obtained and used as a mixture together with its by-product, 2-methyl- 1,2- isothiazolin-3-one, and each is isolated. However, the present invention can also be used as a mixture thereof.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0043

[Correction method] Change

[Correction content]

Further, the antibacterial and antifungal preparation of the present invention exhibits a sufficient antifungal effect by the mixture of the compound A and the compound B, but if necessary, a general antibacterial and antifungal agent such as 2- (4-thiazolyl) benzimidazole, parachlorometaxylenol, parachlorometacresol,
2,3,5,6-tetrachloro-4- (methylsulfonyl) pyridine, N-dichlorofluoromethyl-N ',
N'-dimethyl-N-sulfamide, 2,4,5,6-
Tetrachloroisophthalonitrile, 3-iodo-2-flop <br/> b Pulse Gill butylcarbamate, 2-bromo-2-bromomethyl glutarate nitrile (1,2-dibromo-2,4
Dicyanobutane), diiodomethyl-p-tolylsulfone, dodecylguanidine hydrochloride and the like can be used alone or in combination of two or more.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0047

[Correction method] Change

[Correction content]

[0047]

[Table 1]

[Procedure Amendment 5]

[Document name to be amended] Statement

[Correction target item name] 0048

[Correction method] Change

[Correction content]

[0048]

[Table 2] ─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] September 29, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0016

[Correction method] Change

[Correction content]

Preferred representative examples of the compound A which can be used in the present invention include 5-chloro-2-methyl-4 -isothiazolin-3-one and 2-methyl- 4 -isothiazolin-3-one or complex compounds thereof. For example, zinc chloride, zinc bromide, zinc iodide, zinc sulfate, zinc acetate, copper chloride, nickel chloride, calcium chloride, magnesium chloride, iron chloride, manganese chloride, sodium chloride, barium chloride, ammonium chloride, and other amine chlorides. The complex compound by is mentioned.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0019

[Correction method] Change

[Correction content]

In the compound A, X is a halogen atom and Y is a lower alkyl group, for example, 5-
Chloro-2-methyl-4 -isothiazolin-3-one is usually obtained and used as a mixture together with its by-product 2-methyl- 4 -isothiazolin-3-one, and even if each is isolated and used. Although good, the present invention can also be used as a mixture thereof.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0047

[Correction method] Change

[Correction content]

[0047]

[Table 1]

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0048

[Correction method] Change

[Correction content]

[0048]

[Table 2]

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Claims (1)

[Claims] 1. Compound A: (Wherein, X represents a hydrogen atom or a halogen atom, and Y represents a lower alkyl group) and an isothiazolone derivative or a complex compound thereof, and a compound B 1,2-benzisothiazolin-3-one or a salt thereof represented by (In the formula, R ₁ , R ₂ and R ₃ may be the same or different and each is a hydrogen atom, a halogen atom, an alkyl group, a hydroxyl group, a cyano group, a thiol group, a nitro group, a carboxyl group, an amino group or a sulfone group. A stable liquid antibacterial and antifungal preparation, characterized by comprising a propanol derivative represented by the formula (1).