JPH02784A - Isothiazolone composition and use thereof - Google Patents

Abstract

PURPOSE:To obtain the prevent composition useful as a germicide, antiseptic, etc., having excellent stability of preparation even by using an aqueous solvent, suitable for long-term preservation comprising an isothiazolone compound, glycol-based solvent, anionic surfactant, etc. CONSTITUTION:The aimed composition consisting of (A) an isothiazolone compound (e.g., 2-methyl-5-chloro-1,2-isothiazolin-3-one) shown by the formula (X is H or halogen; Y is lower alkyl), (B) a glycol-based solvent (e.g., ethylene glycol) in an amount at least enough to dissolve the compound shown by the formula and (C) an anionic surfactant (preferably sodium alkyldiphenyl ether disulfonate or sodium alkylbenzenesulfonate) and/or a nonionic surfactant (preferably adduct of sorbitan fatty acid ester with ethylene oxide) having >=10 HLB.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application This invention relates to a method for producing an aqueous isothiazolone preparation and an isothiazolone composition useful for the production. More specifically, isothiazoline, which is useful as a non-medical disinfectant,
The present invention relates to a method for producing an aqueous preparation containing a 3-one compound and particularly useful for antiseptic and antifungal treatment of various synthetic polymer emulsions, and a composition useful for this production.

(b) Prior art Isothiazolone compounds such as 5-chloro-2-methyl-isothiazolin-3-one and 2-methyl-isothiazolin-3-one have traditionally been used as non-medical disinfectants, preservatives and
It is known as a fungicide, and is particularly useful as a preservative and fungicide for synthetic polymer emulsions such as NBR latex, SBR latex, and acrylic resin emulsions.

Since this isothiazolone compound is easily soluble in water, it is desirable to use it as an aqueous solution formulation, taking into consideration its dispersion in the target system.However, isothiazolone compounds are hydrolyzed in water in a short time, so In aqueous solution, it is extremely unstable as a formulation and cannot be used in actual basolateral use.

Therefore, conventionally, aqueous formulations have been created in which isothiazolone compounds are dissolved as a complex with metal salts such as calcium salts and magnesium salts in water or aqueous solvents to impart stability, and 'isothiazolone compounds are dissolved in large amounts of organic solvents. Organic solvent formulation with significantly reduced water content (JP-A-61-
No. 56174 and AT-212576) have been proposed.

(c) Problems to be Solved by the Invention However, when an effective amount of the above conventional aqueous preparation is directly added to a synthetic polymer emulsion as a preservative/antifungal agent, many of the calcium, magnesium, etc. contained in the preparation are There is a problem in that the emulsion phase is destroyed by the action of valent metal ions, resulting in phase separation and coagulation (so-called emulsion shock).

Therefore, when using such an aqueous preparation, it is necessary to sufficiently dilute it before adding it, but this causes inconveniences such as quality deterioration such as variation in latex of the synthetic polymer emulsion to be added. In addition, coagulation sometimes occurred when diluted and used. There is also a proposal to use this aqueous preparation in a synthetic polymer emulsion without diluting it, but in this case it was necessary to add a specific anionic surfactant (Japanese Patent Laid-Open No. 60-65042, 60-96652).

On the other hand, when the above-mentioned organic solvent preparation is added to a synthetic polymer emulsion, the organic solvent may be partially brought into the system at a high concentration, resulting in shock.

The present invention has been made under such circumstances, and is particularly directed to the production of an isothiazolone aqueous formulation which has excellent formulation stability and which does not cause stagnation even when directly added to a synthetic polymer emulsion. The present invention seeks to provide a method and a raw material composition useful for its production.

(d) Means for solving the problem From the above point of view, the present inventors have conducted extensive research and examination, and have found that an aqueous solvent solution of an unstable isothiazolone compound;
In particular, the stability of a water-glycol solvent solution can be significantly improved by adding a specific surfactant to the solution, and even if this aqueous preparation is added to a polymer emulsion in an effective amount for preservative and anti-mold. We have discovered the fact that no negative effects such as so-called shocks occur.

Thus, according to the present invention, (a) an isothiazolone-3-one compound represented by the general formula (I): (wherein, X represents a hydrogen atom or a halogen atom, and Y represents a lower alkyl group); b) an isothiazolone composition comprising a glycol solvent in an amount sufficient to at least dissolve the compound of general formula (1); and (c) an anionic surfactant and/or a nonionic surfactant with an HLB I of 0 or more. , diluted with water,
(a) General formula (
an isothiazolone compound represented by I), (b) a water-glycol aqueous solvent in an amount sufficient to at least dissolve the compound of general formula ([), and (c) an anionic surfactant and/or ) (LB 10 A method for producing an aqueous isothiazolone preparation is provided, which is characterized by obtaining an acidic aqueous preparation comprising the above nonionic surfactant.

The aqueous formulation thus obtained is a solution formulation that is endowed with excellent formulation stability without substantially containing calcium or magnesium salts that have been conventionally used for stabilization.

Examples of the halogen atom of the substituent X in the compound of formula (1) used in this invention include a chlorine atom, a bromine atom, and an iodine atom, with a chlorine atom being preferred. On the other hand, as the lower alkyl group of the substituent Y, an alkyl group having 1 to 6 carbon atoms (for example, methyl, ethyl, propyl, butyl, etc.)
is included. Preferred is a methyl group. These formulas (
A preferred representative example of the compound 1) is 2-methyl-5
-chloro-1,2-isothiazolin-3-one and 2
-Methyl-1,2-isothiazolin-3-one.

These isothiazolone compounds were published in Japanese Patent Publication No. 46-1272.
It can be produced according to the synthesis method described in Publication No. 3, and is usually obtained as a mixture of the above compounds. Mixtures of these are also suitable for use with this invention.

As the anionic surfactant used in this invention, sulfonate salt type, sulfate ester salt type, phosphate ester salt type, or polymeric polymer anionic surfactant can be suitably used.

The above-mentioned sulfonate-based anionic surfactants include dialkyl sulfosuccinates, alkanesulfonates, hydroxyalkanesulfonates, linear alkylbenzene sulfonates, branched alkylbenzene sulfonates, alkyldiphenyl ether sulfonates, alkyl Examples include naphthalene sulfonate, alkylphenoxypolyoxyethylene propyl sulfonate, polyoxyethylene alkyl-sulfophenyl ether salt, sodium N-methyl-N-oleyl taurate, petroleum sulfonate, and the like.

As the above-mentioned sulfate ester salt-based anionic surfactant,
Sulfated tallow oil, fatty acid alkyl ester sulfate, alkyl sulfate, polyoxyethylene alkyl ether sulfate, fatty acid monoglyceride sulfate, polyoxyethylene alkylphenyl ether sulfate, polyoxyethylene styryl phenyl ether sulfate Examples include salt.

Examples of the above-mentioned phosphoric acid ester salts include phosphoric acid ester salts of higher alcohols, phosphoric acid ester salts of higher alcohol ethylene oxide adducts, and the like.

As the polymeric polymer surfactant mentioned above, styrene-
Examples include saponified maleic anhydride copolymer, partially saponified olefin-maleic anhydride copolymer, and naphthalene sulfonate-formalin condensate.

The cation constituting the salt of the anionic surfactant is suitably an alkali metal or ammonium, with sodium being preferred.

Among the anionic surfactants mentioned above, preferred are disodium alkyl diphenyl ether disulfonate represented by the following formula: (wherein R is an alkyl group of C2 to C1), sodium alkylbenzene sulfonate, and higher alcohols. Examples include sodium sulfate, sodium alkyl phenyl ether sulfate, sodium polyoxyethylene alkyl ether phosphate, sodium polyoxyethylene styryl methyl phenyl ether phosphate, and naphthalene sulfonate-formalin condensate.

On the other hand, as the nonionic surfactant having an HLB of 10 or more, polyethylene glycol-based or polyhydric alcohol-based nonionic surfactants can be suitably used.

Examples of the polyethylene glycol nonionic surfactants include higher alcohol ethylene oxide adducts, alkylphenol ethylene oxide adducts, fatty acid ethylene oxide adducts, polyhydric alcohol fatty acid ester ethylene oxide adducts, ethylene oxide adducts of fats and oils, and polypropylene glycol ethylene. Examples include oxide adducts.

As the above polyhydric alcohol nonionic surfactant,
Examples include fatty acid esters of glycerin, fatty acid esters of pentaerythritol, fatty acid esters of sorbitol and sorbitan, fatty acid esters of sucrose, and alkyl ethers of polyhydric alcohols.

Preferred among these nonionic surfactants are higher alcohol ethylene oxide adducts, alkylphenol ethylene oxide adducts, polypropylene glycol ethylene oxide adducts, and sorbitan fatty acid ester ethylene oxide adducts.

As the glycol solvent in this invention, lower alkylene glycols such as ethylene glycol, diethylene glycol, propylene glycol, and dipropylene glycol, and their mono-lower alkyl ethers can be used. Formaldehyde condensates of can also be used.

In this invention, first, an isothiazolone composition consisting of a glycol solvent solution containing the isothiazolone compound and a surfactant is prepared, and then this is diluted with water and the pH is adjusted as necessary to form an isothiazolone aqueous preparation. is manufactured.

Here, the pH is adjusted when the liquid is neutral or alkaline, and the preferred pH is 2 to 5.

Further, as the water for dilution, ordinary water such as tap water, soft water, pure water, etc. can be used, and industrial water etc. can also be used. The amount of water to be diluted is usually preferably 0.1 to 10 times the amount (volume) of the isothiazolone composition.

The amount of the compound of formula (1) to be used is adjusted to be 1-15% by weight in the final aqueous preparation, and is appropriately determined depending on the intended use.

The blending amount of the surfactant is 0.1 to 20 parts by weight per 1 part by weight of the compound of formula (1). If the amount is less than 0.1 part by weight, the isothiazolone compound is likely to decompose, and an aqueous pharmaceutical composition with good storage stability cannot be obtained, which is not preferable. Further, even if more than 20 parts by weight is added, it is not suitable because the effect of negating the economic disadvantages cannot be obtained. usually,
The amount is preferably 0.5 to 10 parts by weight per 1 part by weight of the compound of formula (1).

The Moeki isothiazolone composition used in this invention is
The composition itself is stable, is useful as a raw material or intermediate when carrying out the method for producing an aqueous preparation of the present invention in the field, and is a novel composition as far as the present inventors know.

Therefore, this invention provides (a) an isothiazolone compound represented by the general formula (I): (wherein, X represents a hydrogen atom or a halogen atom, and Y represents a lower alkyl group); and (b) an isothiazolone compound represented by the general formula (I): The present invention also provides an isothiazolone composition comprising a glycol solvent in an amount sufficient to at least dissolve the compound of (1), and (c) an anionic surfactant and/or a nonionic surfactant with an HLB of 10 or more. be. The amount of the compound of formula (1) in such a composition is at least within a range that can be dissolved in the glycol solvent. Specifically, as mentioned above, it is suitable to adjust the amount to 1 to 15% by weight in the aqueous preparation finally obtained by dilution, and usually 1.5 to 15% by weight in the above composition before dilution. A suitable content is 30% by weight. The amount of the surfactant to be blended is as described above for compound 1 of formula (1).
The amount is 0.1 to 20 parts by weight.

The aqueous preparation obtained by the production method of the present invention does not use polyvalent metals, and also does not use organic solvents at all or in a significantly reduced amount, so sysdic when added to the synthetic polymer emulsion is reduced. This will be prevented or suppressed. The unique action of the surfactant in the formulation, which is different from the general surfactant action and solubilization action, prevents or suppresses the decomposition of the isothiazolone compound itself, resulting in excellent formulation stability as an aqueous formulation. The Rukoto.

Note that the effect of the above-mentioned specific surfactant on suppressing the decomposition of isothiazolone compounds is not clear.

However, the mechanism of decomposition of isothiazolone in water is considered as follows. For example, 5-chloro-2-methyl-isothiazolin-3-one becomes 2-methyl-isothiazolin-3-one by dechlorination, and then by desulfurization, a linear amide compound with no bactericidal effect is produced. This chain compound further promotes the decomposition of 5-chloro-2-methyl-isothiazolin-3-one.

Therefore, the above-mentioned surfactant is thought to inhibit the electrophilic reaction of the nitrogen moiety and the nucleophilic reaction of the sulfur moiety of isothiazolone, thereby preventing ring-opening decomposition of the isothiazolone ring.

(E) Example Reference Example 1 2-Methyl-5-rimyl-isothiazolin-3-one 2
．． 9 parts by weight and 0 parts by weight of 2-methyl-isothiazolin-3-one
．． 7 parts by weight, 66.4 parts by weight of water and disodium alkyl diphenyl ether disulfonate [NEWCOL271A manufactured by Nippon Nyukazai Co., Ltd., containing active ingredients ff14]
5% and the remainder 130 parts by weight of water (purity part: 13.5 parts by weight) were mixed and stirred, and the pH was adjusted to 3 using mineral acid.
I got 1.

Reference Examples 2 to 24 and Comparative Examples Preparation product No. 2 to 2 prepared by blending each compound listed in Table 1 and adjusting the pH to 2 to 5 in the same manner as in Example 1.
No. 4 (reference example) and No. 25-35 (comparative example) were obtained. (All numbers in the table indicate parts by weight, and the number in parentheses for the amount of surfactant used indicates the pure mixing ratio with respect to 1 part by weight of the preservative and antifungal agent.)

Storage stability test method The formulation was placed in a glass container and left at 40°C.

Observe the condition over time, and if there is no change in appearance and the decomposition rate is 10% or less as measured by HPLC measurement, ○, if it becomes cloudy and the decomposition rate is 10 to 20% by HPLC measurement, Δ, if precipitation occurs,
Those with a decomposition rate of 20% or more as determined by HPLC measurement were rated X.

Shock test for polymer emulsions Polymer emulsions (two types of SBR latex and acrylic resin emulsion) were placed in beakers each having a capacity of 100 x 12.200112, and the formulation was added to the beaker.

After stirring with a magnetic stirrer for 3 minutes, the mixture was filtered through a 100-mesh wire mesh. O1 that does not leave aggregates on the wire mesh
Those in which aggregates remained were marked as ×. The test results are also shown in Table 2.

From this result, the aqueous formulation of this invention has excellent stability and
It was also found to be an excellent product that does not have any adverse effects on polymer emulsions.

Table 2 Table 2 (continued) Example 1 2-Methyl-5-chloro-isothiazolin-3-one 5
, 1 and 2-methyl-isothiazolin-3-one 1
．． 53.9 parts by weight of ethylene glycol and nonylphenol ethylene oxide adduct (H
LB 13J) 40 parts by weight were mixed and stirred to obtain formulation N.
o, I got A.

Example 2 53.9 parts by weight of ethylene glycol in Example I was mixed with 83.9 parts by weight of ethylene glycol.
40 parts by weight of nonylphenol ethylene oxide adduct was added to 9 parts by weight, and in the same manner as in Example 1 except for the above, preparations No. and B were obtained.

Example 3 A formulation was prepared in the same manner as in Example 2, except that instead of 83.9 parts by weight of ethylene glycol in Example 2, a mixture of 43.9 parts by weight of ethylene glycol and 40 parts by weight of ethylene glycol formaldehyde condensate was used. Product No. C was obtained.

Each of the above formulations was diluted with water to a ratio of 1:1 and stirred to obtain a homogeneous aqueous solution. The respective diluted liquids are designated as Preparation No., ■, Preparation No., ■, and Preparation No. Q, respectively.

Storage stability tests and shock tests for polymer emulsions for each formulation [Test methods are described above (P/KA
-3321)] The test results are also shown in Table 3.

(F) Effects of the Invention According to the production method of the present invention, the formulation has excellent stability despite using an aqueous solvent, and can be stored for a long period of time.
It is possible to obtain an aqueous isothiazolone formulation that is extremely suitable for transportation and the like. The aqueous preparation thus obtained can be used as it is by being added to the emulsion without adversely affecting the synthetic polymer emulsion, such as conventional aqueous preparations or organic solvent preparations.

Therefore, the production method of the present invention is extremely useful in practice as a method for producing liquid drugs for the purpose of preserving and preventing mold.

On the other hand, the isothiazolone composition of the present invention can be used as a raw material for carrying out the above-mentioned production method of the present invention, and in particular, can be used as a raw material when carrying out the process on-site, thereby making handling such as transportation and storage easier. As mentioned above, this is extremely useful in practice.

Claims (1)

[Claims] 1. (a) General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・(I
) (However, in the formula, X represents a hydrogen atom or a halogen atom, and Y represents a lower alkyl group.) An isothiazolone compound represented by (b) an amount sufficient to at least dissolve the compound of the above general formula (I). An isothiazolone composition comprising: a glycol solvent; and (c) an anionic surfactant and/or a nonionic surfactant with an HLB of 10 or more. 2. The anionic surfactant is disodium alkyl diphenyl ether disulfonate, sodium alkylbenzene sulfonate, sodium higher alcohol sulfate, sodium alkylphenyl ether sulfate, sodium polyoxyethylene alkyl ether phosphate, or polyoxyethylene styryl methyl phenyl ether. The composition according to claim 1, which is a sodium phosphate ester. 3. The composition according to claim 1, wherein the nonionic surfactant is an ethylene oxide adduct, an alkylphenol ethylene oxide adduct, a higher alcohol ethylene oxide adduct, or a polypropylene glycol ethylene oxide adduct of fatty acid ester of sorbitan. . 4. (a) General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・(I
) (However, in the formula, X represents a hydrogen atom or a halogen atom, and Y represents a lower alkyl group.) An isothiazolone compound represented by (b) an amount sufficient to at least dissolve the compound of the above general formula (I). By diluting an isothiazolone composition consisting of a glycol solvent and (c) an anionic surfactant and/or a nonionic surfactant with an HLB of 10 or more with water and adding a mineral acid as necessary, (a ) General formula (
I) an isothiazolone compound represented by formula (I); (b) an aqueous water-glycol solvent in an amount sufficient to at least dissolve the compound of general formula (I); and (c) an anionic surfactant and/or a nonionic surfactant with an HLB of 10 or more. surfactant,
A method for producing an aqueous isothiazolone preparation, characterized by obtaining an acidic aqueous preparation consisting of. 5. Anionic surfactant and/or nonionic surfactant in an amount of 0.1 to 1 part by weight of the compound of general formula (I)
5. The manufacturing method according to claim 4, wherein the amount is 20 parts by weight. 6. Anionic surfactant and/or nonionic surfactant in an amount of 0.5 to 1 part by weight of the compound of general formula (I)
5. The manufacturing method according to claim 4, wherein the amount is 10 parts by weight. 7. The manufacturing method according to claim 4, wherein the compound of general formula (I) is prepared in an aqueous preparation so as to be incorporated in an amount of 1 to 15% by weight. 8. The manufacturing method according to claim 4, wherein the liquid is adjusted to have a pH of 2 to 5.