Aqueous isothiazolone formulation

Abstract: An aqueous isothiazolone formulation useful for antiseptic or antifungal treatment of various synthetic polymeric emulsions, which comprises (a) a specific isothiazolone compound, (b) water or an aqueous solvent and (c) a specific nitrobromo or cyanobromo compound.

Description: BACKGROUND OF THE INVENTION Field of the Invention The present invention concerns a stabilized aqueous isothiazolone formulation. More in particular, it relates to an aqueous formulation containing an isothiazolin-3-one compound which is useful as non-medicinal biocide and, in particular, useful for antiseptic or antifungal treatment of various synthetic polymeric emulsions. Description of the Prior Art Isothiazolone compounds such as 5-chloro-2-methyl-isothiazolin-3-one and 2-methyl-isothiazolin-3-one have been known so far as non-medicinal biocide, antiseptic or antifungal agent which are useful, in particular, as antiseptic or antifungal agent for synthetic polymeric emulsions such as NBR latex. SBR latex or acrylic resin emulsion. Since the isothiazolone compounds are easily water soluble, it is desirable to use them in the form of an aqueous solution in view of dispersion into systems to be treated, inflammability of products and also from an economical point of view. Referring to the inflammability, those products formulated only with a glycol solvent exhibit inflammability. A sufficient care has to be taken for inflammable products so as to prevent the occurrence of fire accident or spread thereof. Therefore, inflammable products are hard to be dealed with, especially in storage or transportation. Accordingly, flashing products are difficult to handle with and non-inflammable products are desired also for biocides. However, since isothiazolone compounds are hydrolyzed in water in a short period of time, a mere aqueous solution thereof is extremely unstable in formulations and cannot be put to practical use at all. In view of the above, an aqueous formulation prepared by forming an isothiazolone compound as a complex with a metal salt such as calcium salt or magnesium salt and then dissolving the complex in water or an aqueous solvent for providing stability or an organic solvent formulation prepared by dissolving an isothiazolone compound in a great amount of organic solvent with a small amount of water thereby remarkably reducing the water content is already known. (Japanese Patent Laid-Open Sho 61-56174 and 61-212576). However, if the conventional aqueous formulation as described above is added as it is in an effective amount as an antiseptic or antifungal agent to a synthetic polymeric emulsion, there is a problem that the emulsion phase is broken to cause phase separation or coagulation (so-called emulsion shock) due to the effect of polyvalent metal ions such as of calcium or magnesium contained in the formulation. Accordingly, it is necessary upon using such an aqueous solution to sufficiently dilute it, but this may cause a disadvantage of lowering the quality such as variation of the latex concentration in the synthetic polymeric emulsion. Further, coagulation may sometimes occur even if the additive is used after dilution. In addition, there has also been proposed the use of such an aqueous formulation without dilution with a synthetic polymeric emulsion, but it is necessary to use a special anionic surface active agent in combination with it (Japanese Patent Laid-Open Sho 60-65042 and Sho 60-96652). Further, if the organic solvent formulation as described above is added to a synthetic polymeric emulsion, the organic solvent introduced locally at a high concentration in the system can cause a shock in some cases. The present invention has been made in view of the foregoing situations and it is an object thereof to provide an isothiazolone compound formulation which is excellent in the stability of the formulation, free from the problem of inflammability inexpensive from an economical point of view, and which causes no shock when added directly to a synthetic polymeric emulsion. Although there has been a suggestion of combining a compound of the ingredient (a) and a compound of a ingredient (c) used in the present invention in a non-aqueous formulation (Japanese Patent Publication Sho 60-54281 and Japanese Patent Laid-Open Sho 63-316702), combination of them in an aqueous formulation and the effect obtained therefrom have not yet been known. SUMMARY OF THE INVENTION In view of the above, the present inventors have made an earnest study and, as a result, have found that an unstable aqueous solution of an isothiazolone compound is remarkably improved in stability without using a metal salt by preparing the formulation with addition of an extremely small amount of a specific bromine compound, and that addition of such an aqueous formulation by an effective antibacterial or antifungal amount to a polymeric emulsion does not result in undesired effect such as shock. Thus, according to the present invention, there is provided the use of a nitrobromo or cyanobromo compound represented by the following formula (II) : where X₁ represents a nitro group or cyano group, Y₁ and Y₂ represent, independently, a bromine atom, nitro group, cyano group, aminocarbonyl group, a lower alkyl group substituted with a bromine atom cyano group or hydroxy group, or a group : where R₁, R₂ and R₃ represent, independently, a lower alkyl group or hydrogen atom, or either one of Y₁ or Y₂ represents : while the other represents a hydrogen or bromine atom or Y₁ and Y₂ are joined together to form in which Y₃ represents a hydrogen or halogen atom, A represents a hydrogen atom, halogen atom, nitro group or a lower alkyl group and m represents an integer of 1 to 3, or Y₁ and Y₂ are joined together to form a dioxane group which may be substituted with a lower alkyl group, for stabilizing an aqueous isothiazolone formulation comprising : (a) an isothiazolone compound represented by the formula (I) where X represents a hydrogen atom or halogen atom and Y represents an alkyl group, (b) water or a mixture of water and a hydrophilic organic solvent in an amount at least sufficient to dissolve the compound of the general formula (I) described above. DESCRIPTION OF THE PREFERRED EMBODIMENTS The aqueous formulation obtained according to the present invention is a solution applied with excellent formulation stability substantially free from calcium or magnesium salt which has been used for the stabilization. In particular, it has been accomplished on the basis of an unexpected finding that the bromine compound functions as a stabilizer. It is known that certain bromine compounds are used in combination with the isothiazolone compound with an aim to a synergistic sterilizing effect (Japanese Patent Publication Sho 60-54281). However, this publication actually discloses only a non-aqueous formulation using them together and, in particular, the publication neither shows nor suggests that the stabilization of the aqueous formulation of the isothiazolone compound can be attained by the incorporation of a small amount of the bromine compound. The halogen atom for the substituent X in the isothiazolone compound of the formula (I) used in the present invention, can be for example, a chlorine atom, a bromine atom or an iodine atom, the chlorine atom being preferred. On the other hand, as the lower alkyl group for the substituent Y, there can be mentioned alkyl groups with 1 to 8 carbon atoms (for example, methyl, ethyl, butyl or octyl), the methyl group being preferred. Preferred typical examples of the isothiazolone compounds of the formula (I) are 2-methyl-5-chloro-1,2-isothiazolin-3-one and 2-methyl-1,2-isothiazolin-3-one. The isothiazolone compounds can be prepared, for example, in accordance with the method of synthesis as described in Japanese Patent Publication Sho 46-12723 and they are usually obtained as a mixture of these compounds as above. Such a mixture can also be used suitably in this invention. In the present invention, the compound of the formula (II) is used as a stabilizer for the formulation. Referring to the lower alkyl group in the definition for the compound (II), alkyl groups with 1 to 8 carbon atoms described above can also be mentioned. Specific examples of the compounds of the formula (II) described above are: tribromonitromethane, 2,2-dibromo-3-nitrilopropionamide, 2,2-dibromo-2-nitroethanol, 1,1-dibromo-1-nitro-2-propanol, 1,1-dibromo-1-nitro-2-acetoxyethane, 1,1-dibromo-1-nitro-2-acetoxypropane, 2-bromo-2-nitro-1,3-diacetoxypropane, 2-bromo-2-nitro-1,3-diformyloxypropane, 2-nitro-2-bromo-1,3-propanediol, 1,2-dibromo-2,4-dicyanobutane, 2,3-dibromopropionnitrile, (1,2-dibromo-2-nitroethyl)benzene, β-bromo-β-nitrostyrene, 1-(1,2-dibromo-2-nitroethyl)-4-chlorobenzene, β-bromo-4-chloro-β-nitrostyrene, β-bromo-β,p-dinitrostyrene, β-bromo-4-methyl-β-nitrostyrene, 5-bromo-5-nitro-1,3-dioxane, and 5-bromo-2-methyl-5-nitro-1,3-dioxane. They may be used either alone or as a combination of two or more of them. Among them, 2-nitro-2-bromo-1,3-propanediol, 2-bromo-2-nitro-1,3-diacetoxypropane, 2-bromo-2-nitro-1,3-diformyloxypropane, 2,2-dibromo-2-nitroethanol, 1,1-dibromo-1-nitro-2-propanol, 2,2-dibromo-3-nitrilopropionamide, tribromonitromethane, 1,2-dibromo-2,4-dicyanobutane, β-bromo-β-nitrostyrene, 5-bromo-5-nitro-1,3-dioxane, or 5-bromo-2-methyl-5-nitro-1,3-dioxane are preferably used in view of the effect of providing the stability. According to the present invention, an aqueous formulation can be prepared by preparing an aqueous solution of the compound of the Formula (I) and adding a required amount of the stabilizing ingredient into the solution. However, the formulation can be prepared with no particular restrictions to such sequence. Water used here as a solvent may be tap water, softened water, purified water, and industrial service water may also be used. Instead of water, it is also possible to use a mixture of water and hydrophilic organic solvent prepared by mixing water with a hydrophilic organic solvent, for example, various known polyols or polyol ether type liquid compounds 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 and tripropylene glycol monomethyl ether; N,N-dimethylformamide, N,N-diethylformamide, N,N-dimethylacetoamide and N-methyl-2-pyrrolidone. When inflammability of the formulation is taken into consideration, water content in the formulation is preferably not less than 5% by weight and, in view of preventing the shock of the synthetic polymeric emulsion, the water content in the formulation is preferably not less than 10% by weight and, particularly preferably, not less than 50% by weight in the formulation. In the case of using the organic solvent as described above for the aqueous formulation, it is possible to prepare a formulation by adding a predetermined amount of the stabilizing ingredient to the solution of the organic solvent of the formula (I) and diluting the formulation with water upon use. In this case, an economical merit in view of transportation is also obtainable. As the organic solvent used for the organic solvent formulation, an amide compound such as N,N-dimethylformamide, N,N-diethylformamide, N,N-dimethylacetamide and N-methyl-2-pyrrolidone is used alone or as a mixture of the amide compound and the glycol solvent described above. This is used preferably in view of the storage stability of the formulation. According to the present invention, the blending amount of the compound of the formula (I) in the aqueous formulation is preferably from 1 to 30% by weight and, more preferably, 1 to 20% by weight in view of the storage stability. The blending amount of the nitrobromo or cyanobromo compound as the stabilizing agent is preferably from 0.001 to 0.1 parts by weight and, more preferably, of not less than 0.004 parts by weight based on one part by weight of the compound of the formula (I) in view of the store stability. However, since the stabilizing effect is usually obtained equally even if it is added by more than 0.1 parts by weight, the compound may be added in a greater amount. If it is less than 0.001 parts by weight, it is not preferred since the isothiazolone compound becomes more hydrolyzable and an aqueous formulation of excellent storage stability cannot be obtained. On the other hand, it may be added by more than 0.1 part by weight but it is preferably added up to 0.1 part by weight from an economical point of view. In the aqueous formulation obtained according to the present invention, since the polyvalent metal is not used and, in addition, the organic solvent is not used or used only at a remarkably reduced amount, shock upon adding to the synthetic polymeric emulsion can be prevented or suppressed. In addition, it is free from inconveniency upon handling such as inflammability. The formulation is inexpensive and can provide excellent stability as the aqueous formulation. Example 1 Formulations of Examples 1B - 56B and Comparative Examples 1A - 75A were prepared by using a mixture of 2-methyl-5-chloro-isothiazolin-3-one and 2-methyl-isothiazolin-3-one (at 9:1 weight ratio) (hereinafter simply referred to as MIT) as an isothiazolone compound, dissolving the mixture in each of the solvents as described in Table 1, and further admixing a stabilizing ingredient under stirring (all of the numerals in the table represent parts by weight). The following tests were carried out for each of the formulation products. (Store Stability Test) Test method --- Each of the formulations was placed in a glass vessel and left at 40°C. The state with lapse of time was observed and the results were expressed as "o" for the formulation showing no decomposition, as "▵" for the formulation showing slight clouding in appearance and MIT decomposition rate of less than 5% as measured by HPLC and as "x" for the formulation showing clouding in view of the appearance due to great amount of crystals deposited and decomposition rate of not less than 5%. It is estimated from the test result for long years that stability for 2 months at 40°C in this test will correspond to the stability at room temperature for more than 6 months. (Shock Test to Polymeric Emulsion) The polymeric emulsion (two kinds of SBR latex and acrylic resin emulsion) was taken in 100 ml and 200 ml volume beakers respectively, to which 3 ml of the formulation was added. After stirring with a magnetic stirrer for 3 min, the content was filtered through 100 mesh metal gage. The specimens showing no coagulation products on the metal gage were expressed as "o" and those leaving coagulation products as "x". The results are shown in Table 1. From the results, it can be seen that the aqueous preparation according to the present invention is excellent in stability and causes no undesired effect on the polymeric emulsion. In the table, abbreviations mean the following compounds. Abbreviation Compound Name DMF N,N-dimethylformamide DEF N,N-diethylformamide DMAA N,N-dimethylacetamide MP N-methyl-2-pyrrolidone EG Ethylene glycol DEG Diethylene glycol PEG-200 Polyethylene glycol (average molecular weight 200) PG Propylene glycol DPG Dipropylene glycol TPG Tripropylene glycol MDG Diethylene glycol monomethyl ether MEG Ethylene glycol monomethyl ether EDG Diethylene glycol monoethyl ether TPM Tripropylene glycol monomethyl ether 1,4-BD 1,4-butanediol 1,5-PD 1,5-pentanediol Example 2 Compounds as shown in the following table were used as the stabilizer and the same tests as in Example 1 were conducted. The results are shown in Table 2. Example 3 Bronopole, DBNPA, BND, BNS and DDB were used as the stabilizer and the same tests as in Example 1 were conducted. The results are shown in Table 3. As can be seen from the foregoing examples and comparative examples, the aqueous isothiazolone formulation according to the present invention is excellent in stability, in particular, storage stability. It causes no undesired effect if added directly to a polymeric emulsion. Accordingly, the formulation is not only convenient upon handling but also enables the extention of the application and form of the use of the isothiazolone compounds.

Claims: The use of a nitrobromo or cyanobromo compound represented by the following formula (II) : where X₁ represents a nitro group or cyano group, Y₁ and Y₂ represent, independently, a bromine atom, nitro group, cyano group, aminocarbonyl group, a lower alkyl group substituted with a bromine atom cyano group or hydroxy group, or a group : where R₁, R₂ and R₃ represent, independently, a lower alkyl group or hydrogen atom, or either one of Y₁ or Y₂ represents : while the other represents a hydrogen or bromine atom or Y₁ and Y₂ are joined together to form in which Y₃ represents a hydrogen or halogen atom, A represents a hydrogen atom, halogen atom, nitro group or a lower alkyl group and m represents an integer of 1 to 3, or Y₁ and Y₂ are joined together to form a dioxane group which may be substituted with a lower alkyl group, for stabilizing an aqueous isothiazolone formulation comprising : (a) an isothiazolone compound represented by the formula (I) where X represents a hydrogen atom or halogen atom and Y represents an alkyl group, (b) water or a mixture of water and a hydrophilic organic solvent in an amount at least sufficient to dissolve the compound of the general formula (I) described above. The use of claim 1 in which the nitrobromo or cyanobromo compound is selected from the group consisting of tribromonitromethane, 2,2-dibromo-3-nitrilopropionamide, 2,2-dibromo-2-nitroethanol, 1,1-dibromo-1-nitro-2-propanol, 1,1-dibromo-1-nitro-2-acetoxyethane, 1,1-dibromo-1-nitro-2-acetoxypropane, 2-bromo-2-nitro-1,3-diacetoxypropane, 2-bromo-2-nitro-1,3-diformyloxypropane, 2-nitro-2-bromo-1,3-propanediol, 1,2-dibromo-2,4-dicyanobutane, 2,3-dibromopropionnitrile, (1,2-dibromo-2-nitroethyl)benzene, β-bromo-β-nitrostyrene, 1-(1,2-dibromo-2-nitroethyl)-4-chlorobenzene, β-bromo-4-chloro-β-nitrostyrene, β-bromo-β,p-dinitrostyrene, β-bromo-4-methyl-β-nitrostyrene, 5-bromo-5-nitro-1,3-dioxane and 5-bromo-2-methyl-5-nitro-1,3-dioxane. The use of claim 1 in which the nitrobromo or cyanobromo compound is selected from the group consisting 2-nitro-2-bromo-1,3-propanediol, 2-bromo-2-nitro-1,3-diacetoxypropane, 2-bromo-2-nitro-1,3-diformyloxpropane, 2,2-dibromo-2-nitroethanol, 1,1-dibromo-1-nitro-2-propanol, 2,2-dibromo-3-nitrilopropionamide, tribromonitromethane, 1,2-dibromo-2,4-dicyanobutane, β-bromo-β-nitrostyrene, 5-bromo-5-nitro-1,3-dioxane and 5-bromo-2-methyl-5-nitro-1,3-dioxane. The use of claim 1 in which the content of the nitrobromo or cyanobromo compound is 0.001 to 0.1 part by weight based on one part by weight of the compound of the formula (I). The use of claim 1 in which the isothiazolone compound of the formula (I) is 2-methyl-5-chloro-1-2-isothiazolin-3-one, 2-methyl-1,2-isothiazolin-3-one or mixture thereof. The use of claim 1 in which the content of the isothiazolone compound of the formula (I) is 1 to 30% by weight in the formulation. The use of claim 1 in which the water content is adjusted to be not less than 5% by weight in the formulation. The use of claim 7 in which the water content is adjusted to be not less than 10% by weight. The use of claim 1 in which the aqueous solvent comprises water and a hydrophilic organic solvent. The use of claim 1 wherein the resulting formulation is used for antiseptic or antifungal treatment of a synthetic polymeric emulsion.

Inventors: ITO YOSUKE, KATAYAMA SAKAE, SANO YOICHI, TSUJI KATSUJI, ITO, YOSUKE, KATAYAMA, SAKAE, SANO, YOICHI, TSUJI, KATSUJI
Applicants: KATAYAMA CHEMICAL WORKS CO, KATAYAMA CHEMICAL, INC.
Application year: 1990
Main classification: A01N43
IPC codes: A01N43, A01N25