A STABILIZED ISOTHIAZOLONE COMPOSITION AND A METHOD OF STABILIZATION OF ISOTHIAZOLONE

Abstract: The present invention relates to a stabilized isothiazolone composition and a method of stabilization of isothiazolone, more particularly, to a stabilized isothiazolone solution comprising (a) isothiazolone composition represented by formula (1), (b) sulfuric acid, and (c) solvent. Wherein, R1 and R2, which are the same or different, respectively represent a hydrogen atom; a halogen atom; or C1-C4 alkyl group; or R1 and R2 together form a cyclic allyl group; R3 represents C1-C10 alkyl group which is substituted or unsubstituted with a hydrogen atom, a halogen atom or hydroxy group; C2-C10 alkenyl group which is substituted or unsubstituted with a halogen atom; C2-C10 alkynyl group which is substituted or unsubstituted with a halogen atom; a halogen atom; C1-C10 alkyl group; or aralkyl group which is substituted or unsubstituted with C2-C9 alkoxy group.

Description: A STABILIZED ISOTHIAZOLONE COMPOSITION AND A METHOD OF STABILIZATION OF ISOTHIAZOLONE BACKGROUND OF THE INVENTION (a) Field of the Invention The present invention relates to a stabilized isothiazolone composition and a method of stabilization of isothiazolone, more particularly, to a stabilized isothiazolone solution comprising (a) isothiazolone compound represented by the following formula 1 , (b) sulfuric acid, and (c) solvent. [formula 1] Wherein, R 1 and R 2 , which may be the same or different, respectively represent a hydrogen atom; a halogen atom; or C, ~ C 4 alkyl group; or R^ and R 2 together form cyclic allyl group; R 3 represents a hydrogen atom; C, ~ C 10 alkyl group which is substituted or unsubstituted with a halogen atom or hydroxy group; C 2 ~ C 10 alkenyl group which is substituted or unsubstituted with a halogen atom; C 2 ~ C 10 alkynyl group which is substituted or unsubstituted with a halogen atom; C, ~ C 10 alkyl group; or aralkyl group which is substituted or unsubstituted with C 2 ~ C 9 alkoxy group. The present invention also relates to a method of stabilization of isothiazolone of the formula 1. (b) Description of the Related Art Since its development by Craw et al. in 1965, isothiazolone compound has been extensively used in many industrial fields as a disinfectant including an antibacterial and antimicrobial agent for dyes, cosmetics, fibers, or plastics, etc. However, since the isothiazolone compound is very unstable and easily degraded by moisture in the air, heat and ultraviolet light, the beneficial properties of the compound may be lost during storage. In order to improve the stability of the isothiazolone compound, several methods have been actively developed, and the typical method is to use a metal salt stabilizer. In U.S. Pat. Nos. 3,870,795 and 4,067,878, for example, metal nitrite or metal nitrate are added to stabilize isothiazolone solutions. But such metal salt stabilizers react with emulsion components in a latex emulsion to produce precipitates. Further, in some cases, chlorine ions in the metal salt may induce corrosion of the system and metal ions may increase the hardness of water to induce scale. Thus, in such cases, the use of the metal salt is undesirable. A preferred disinfectant should be stable during use, but should be quickly degraded after use so as not to induce the secondary environmental problem. Accordingly, there is a need for a stabilizer satisfying these requirements. SUMMARY OF THE INVENTION It is an object of the present invention to provide a stabilized isothiazolone solution that is useful as a disinfectant and antimicrobial agent, has high stability and can contain active ingredient in high concentration. It is another object of the present invention to provide a method of stabilization of isothiazolone which can stabilize isothiazolone longer than the conventional method using ferric salt, substantially prevents the formation of nitrosamine and precipitates, substantially prevents heavy metals from being discharged to the environment, substantially prevents ions such as Mg 2+ from binding to ions contained in the industrial water such as P0 4 3' , C0 3 2" to form a Hard Scale and does not use stabilizers comprising ferric salts. In order to achieve these object, the present invention provides a stabilized isothiazolone composition comprising (a) isothiazolone compound represented by the following formula 1 , (b) sulfuric acid, and (c) solvent. [formula 1] Wherein, R and R 2 , which may be the same or different, respectively represent a hydrogen atom; a halogen atom; or a C, ~ C 4 alkyl group; or R 1 and R 2 together form a cyclic allyl group; R 3 represents a hydrogen atom; C, ~ C 10 alkyl group which is substituted or unsubstituted with a halogen atom or hydroxy group; C 2 ~ C 10 alkenyl group which is substituted or unsubstituted with a halogen atom; C 2 ~ C 10 alkynyl group which is substituted or unsubstituted with a halogen atom; C 1 ~ C 10 alkyl group; or aralkyl group which is substituted or unsubstituted with C 2 ~ C 9 alkoxy group. The present invention also provides a method of stabilization of isothiazolone comprising stabilizing isothiazolone by blending isothiazolone and a stabilizer, wherein said isothiazolone is the compound represented by the formula 1 , the stabilizer is sulfuric acid. The present invention also provides a- method of sterilization of bacteria and/or fungi and/or algae or suppression of the growth thereof comprising applying disinfectant compositions in the area that is contaminated or contamination-vulnerable by bacteria and/or fungi and/or algae, wherein said disinfectant compositions are the stabilized isothiazolone solutions comprising (a) isothiazolone compound represented by the formula 1 , (b) sulfuric acid and (c) solvent. DETAILED DESCRIPTION AND THE PREFERRED EMBODIMENTS Upon having endeavored to solve the problem of the conventional method of stabilization of isothiazolone, inventors of the present invention found that, if sulfuric acid is added as stabilizers, the degradation of isothiazolone can be prevented, and completed the present invention. The stabilized isothiazolone solution of the present invention comprises isothiazolone compound represented by the formula 1 , sulfuric acid and solvent. The isothiazolone compound which may be used in the present invention includes one or more compounds selected from the group represented by formula 1 , preferably one or more compounds selected from the group consisting of 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4- isothiazolin-3-one, 4,5-dichloro-2-methyl-4-isothiazolin-3-one, 5-chloro-2-n- octyl-4-isothiazolin-3-one, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one and benzoisothiazolin-3-one. It is more preferable to use 5-chloro-2-methyl-4- isothiazolin-3-one or 4,5-dichloro-2-methyl-4-isothiazolin-3-one alone or a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin- 3-one. When using a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, the weight ratio is preferably about 50:50 ~ 99:1 , more preferably about 60:40 ~ 95:5. In addition, it is also preferable to use a mixture comprising 2-methyl-4-isothiazolin-3-one as an active ingredient and a small amount of 5-chloro-2-methyl-4-isothiazolin-3-one. In such case, the weight ratio is preferably about 99.5:0.5 ~ 90:10, more preferably about 98:2 ~ 96:4. The sulfuric acid used as stabilizer in the stabilized isothiazolone solution of the present invention preferably has high purity.. The solvent contained in the stabilized isothiazolone solution can be any type of solvent which can effectively disperse the isothiazolone compound and sulfuric acid. Preferably the solvent is water. The amount of solvent can be varied according to the use of the stabilized isothiazolone solution. And, if the purpose is only storage, the solvent may not be used. The stabilized isothiazolone solution according to the present invention may be made in the form of concentrated solution or diluted solution according to the purpose. When stabilized isothiazolone is employed in exceptional cases such as mass shipments, more concentrated solutions may be used. The isothiazolone solution comprises about 0.00001 ~ 99 wt % of one or more compounds selected from isothiazolone represented by formula 1 , 0.00001 ~ 99 wt % of stabilizer, and less than 99.99998 wt % of solvent. Preferably, it comprises 0.1 - 40 wt % of one or more compounds selected from isothiazolone represented by formula 1 , 0.1 ~ 99 wt % of stabilizer, and 99.8 wt % or less of solvent. Most preferably, it comprises 1 ~ 30 wt % of one or more compounds selected from isothiazolone represented by formula 1 , 5 ~ 99 wt % of stabilizer, and 94 wt % or less of solvent. Conventional isothiazolone solution using metal salt stabilizer can contain at most 14 wt % of active ingredient isothiazolone, while the stabilized isothiazolone solution of the present invention can contain up to 40 wt % of isothiazolone. The amount of stabilizer may vary according to the conditions of use and the concentration of isothiazolone in a mixture; preferably, the weight ratio of isothiazolone : stabilizer is in the range of 1 :0.01 ~ 1 :1 ,000. This range is preferable in terms of stability and cost-saving. In the case of a concentrated solution, the weight ratio of isothiazolone : stabilizer is preferably in the range of 1 :0.02 ~ 1 :50. Even though more amount of stabilizer may be used, this is uneconomical. In the case of an extremely diluted isothiazolone solution (about 1 ~ 10,000 ppm of isothiazolone in solvent), the weight ratio of isothiazolone : stabilizer is preferably in the range of 1:0.1 ~ 1 :20, more preferably in the range of 1:0.1 ~ 1:10. As aforementioned, the stabilized isothiazolone solution according to the present invention is very stable in the air, its efficacy may be sustained under a relatively prolonged period of time in storage, and it forms smaller precipitates than the conventional isothiazolone solution using metal salt stabilizer. Further, the stabilized isothiazolone solution according to the present invention exhibits excellent antimicrobial activities when the effective amount of the solution is applied to the area that is contaminated or contamination-vulnerable by microbes, and removes the hard scale forming factor. In particular, it has the merit that it is dissolved quickly and does not induce the secondary environmental problem when discharged. In other words, the stabilized isothiazolone solution may be extensively used in the following fields: germicidal agents, sanitary aids, purifier, deodorizer, soap in the form of liquid or powder, anti-oil and anti- greasing agents, chemical products for the treatment of foods, daily chemical products, food protectives, protectives for animal feeds, wood protectives, dyes, lazures, flavoring agents, medical preservatives including hospital, metal agents, dyeing solutions, cooling water, air purifier, petroleum manufacture, paper-treatment, anti-slime agent at a paper mill, petroleum products, adhesives, fibers, paint slurry, latex, treatment for leather articles, petroleum fuels, laundry disinfectants, blending feeds for farming, ink, mining, non-woven fabric, petroleum reservoirs, paste material, rubber, sugar refining, tobacco, swimming pool, cosmetics, commodities for toilet, pastes, plastics, cardboard, pharmaceuticals, chemical toilet paper, household laundries, additives for diesel fuel, wax, cork, lubricants, commodities for construction, blending or polishing agents for concrete; it may also be used in the area that is contaminated or contamination-vulnerable by bacteria, fungi or algae and in the places containing organic materials and water where undesirable microorganisms may grow. The present invention is explained in more detail by the following examples, but the claims are not limited to these examples. Isothiazolone solutions obtained from the following examples and comparative example, were respectively left in a thermostat at 65 ° C to measure their thermal stabilities. The degree of degradation was measured by high performance liquid chromatography (HPLC). The thermal stability was measured at 65 ° C . In general, the thermal stability measured at 65 ° C during one week corresponds to that measured at 25 ° C during 7 months. [EXAMPLE 1] Stabilized isothiazolone solution was prepared by blending 25 wt % of an isothiazolone mixture comprising 5-chloro-2-methyl-4-isothiazolin-3-one chlorate and 2-methyl-4-isothiazolin-3-one chlorate, 75 wt % of the aqueous solution comprising 98 wt % sulfuric acid, without using metal salt stabilizer. The presence of precipitates in the prepared solution was observed by naked eye with the lapse of time. The results of residual contents(%) and formed precipitates with the lapse of time are represented in the following table 1. [Table 1] [EXAMPLE 2] Stabilized isothiazolone solution was prepared by blending 25 wt % of 4,5-dichloro-2-methyl-4-isothiazolin-3-one, 75 wt % of the aqueous solution comprising 98 wt % sulfuric acid, without using metal salt stabilizer. The presence of precipitates in the prepared solution was observed by naked eye with the lapse of time. The results of residual contents(%) and formed precipitates with the lapse of time are represented in the following table 2. [Table 2] [EXAMPLE 3] Stabilized isothiazolone solution was prepared by blending 25 wt % of a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one chlorate and 2-methyl- 4-isothiazolin-3-one chlorate, 65 wt % of the aqueous solution comprising 98 wt % sulfuric acid, and 10 wt % of deionized water, without using metal salt stabilizer. The results of residual contents(%) with the lapse of time are represented in the following table 3. , [Table 3] [EXAMPLE 4] Stabilized isothiazolone solution was prepared by blending 25 wt % of a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one chlorate and 2-methyl- 4-isothiazolin-3-one chlorate, 52 wt % of the aqueous solution comprising 98 wt % sulfuric acid, and 23 wt % of phosphoric acid, without using metal salt stabilizer. The results of residual contents(%) with the lapse of time are represented in the following table 4. [Table 4] [EXAMPLE 5] In order to measure the stability of isothiazolone solution of high concentration, isothiazolone solution was prepared by blending 32 wt % of a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one chlorate and 2-methyl-4- isothiazolin-3-one chlorate, 68 wt % of the aqueous solution comprising 98 wt % sulfuric acid, without using metal salt stabilizer, and the presence of precipitates in the prepared solution was observed by naked eye with the lapse of time. The results of active ingredient contents(wt %) and formed precipitates with the lapse of time are represented in the following table 5. [Table 5] The data in table 5 indicates that the stabilized isothiazolone solution is very stable despite of containing 18 wt % or more of active ingredient. In table 5, the reason why the contents of the active ingredient between 14th and 28th is higher than that in the beginning is that water is evaporated because the stability test in this example is carried out in a thermostat at 65 TJ . [EXAMPLE 6] Isothiazolone solution was prepared by blending 2 wt % of a mixture of 5-chloro-2-methyl-4-isothiazoline chlorate and 2-methyl-4-isothiazolin-3- one chlorate, 2 wt % of the aqueous solution comprising 98 wt % sulfuric acid, and 96 wt % of deionized water, without using metal salt stabilizer. The results of residual contents(%) under 50 ° C thermostable condition with the lapse of time are represented in the following table 4. [Table 6] [EXAMPLE 7] Isothiazolone solution was prepared by blending 10 wt % of a mixture of 5-chloro-2-methyl-4-isothiazoline chlorate and 2-methyl-4-isothiazolin-3- one chlorate, 30 wt % of the aqueous solution comprising 98 wt % sulfuric acid, and 60 wt % of deionized water, without using metal salt stabilizer. The results of residual contents(%) under 50 ° C thermostable condition with the lapse of time are represented in the following table 7. [Table 7] Comparative Example Isothiazolone solution was prepared by blending 14 wt % of an isothiazolone mixture comprising 5-chloro-2-methyl-4-isothiazolin-3-one chlorate and 2-methyl-4-isothiazolin-3-one chlorate in a weight ratio of 3:1 and 10 wt % of metal nitrate as stabilizer. The results of residual contents(%) with the lapse of time are represented in the following table 8. [Table 8] The data in tables 1 to 8 indicate that both the stabilized isothiazolone solution of the present invention and the conventional isothiazolone solution using metal salt stabilizer remain stable for a long period. However, the conventional isothiazolone solution using metal salt stabilizer can contain at most 14 wt % of active isothiazolone, while the stabilized isothiazolone solution of the present invention may contain active isothiazolone more than 18 wt % as shown in the example 5. [Test 1] The test of dissociation In order to measure the speed of dissociation of the stabilized isothiazolone solution of the present invention in water, isothiazolone solutions prepared in the example 1 and comparative example were respectively poured into deionized water such that he concentrations of active isothiazolone amount to 100 ppm, and the residual contents(ppm) with the lapse of time were measured. The results were represented in the following table 9. [Table 9] The results in table 9 indicate that the stabilized isothiazolone solution of the present invention was dissociated in water more rapidly than isothiasolone solution using metal salt stabilizer. The above result means that the isothiazolone solution of the present invention is less likely to induce the environmental problem than that of comparative example, because its medicinal efficacy sustains for a certain period of time and it dissociates rapidly. [Test 2] MIC test against microorganisms In order to measure the effect of the stabilized isothiazolone solution of the present invention, isothiazolone solutions prepared in the example 1 and comparative example were respectively poured into deionized water such that the concentrations of active isothiazolone amount to 14 wt %, and the test of MIC(minimum inhibitory concentration) against microorganism was carried out. The results were represented in the following table 10. MIC test was carried out in the following manner: Isothiazolone solutions of the example 1 and comparative example were diluted by double continue dilution method using 96 multi-well plates, then microorganisms were added to a plate in concentration of 10,000 CFU/ml, plates were incubated at 30 ° C for 48 hours, and the growth of microorganisms were determined by naked eye on the basis of turbidity. The media used in this test Tryptic Soy Broth(Difco Co.) for bacteria and Patato Dextrose Broth(Difco Co) for fungi. The strains used in this test were Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 11229, Pseudomonas aeruginasa ATCC 15442, Pseudomonas oleoverans ATCC 8062, Aspergillus niger ATCC 9642, Rhizopus oryzae ATCC 10404, Pullularia pullulans ATCC 9384. [Table 10] The result of table 10 indicates that both the stabilized isothiazolone solution of the present invention and the conventional isothiazolone solution have excellent sterilizing effect against microorganism, and that the degrees of the sterilization of both solutions are comparable. As - explained- above, ..-the present, invention has the effects of stabilizing the active ingredient for a long term without forming precipitates in contrast to the conventional metal salt stabilizer and, if necessary, preparing a stabilized isothiazolone solution of high concentration. In addition, the conventional metlal salt stabilizer may form nitrosamine in product by nitrite ion derived from metal nitrate ion under acidic condition, while the present invention can stabilize isothiazolone solution without using metal salt stabilizer thereby preventing the formation of nitrosamine in product. Further, since isothiazolone solution prepared in accordance with the present invention does not contain metal ion, it prevents heavy metals such as Cu 2+ from being discharged to the environment, and prevents ions such as Mg 2+ from binding to the ions contained in the industrial water such as PO 4 3" , CO 3 2" to form Hard Scale. Thus isothiazolone solution of the present invention does not induce secondary environmental pollution and is able to be effectively used in the field of water treatment where a Hard Scale is a serious problem.

Claims: WHAT IS CLAIMED IS: 1. A stabilized isothiazolone composition comprising (a) isothiazolone compound represented by the following formula 1 , (b) sulfuric acid, and (c) solvent. [formula 1] Wherein, R., and R 2 , which are the same or different, respectively represent a hydrogen atom; a halogen atom; or C, ~ C 4 alkyl group; or R., and R 2 together form cyclic allyl group; R 3 represents a hydrogen atom; C, ~ C 10 alkyl group which is substituted or unsubstituted with a halogen atom or hydroxy group; C 2 ~ C 10 alkenyl group which is substituted or unsubstituted with a halogen atom; C 2 ~ C 10 alkynyl group which is substituted or unsubstituted with a halogen atom; C 1 ~ C 10 alkyl group; or aralkyl group which is substituted or unsubstituted with C 2 ~ C 9 alkoxy group. 2. The stabilized isothiazolone composition according to claim 1 , wherein the isothiazolone compound is selected from the group consisting of 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, 4,5- dichloro-2-methyl-4-isothiazolin-3-one, 5-chloro-2-n-octyl-4-isothiazolin-3-one, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, benzoisothiazolin-3-one and the mixture thereof. 3. The stabilized isothiazolone composition according to claim 1 , wherein the isothiazolone compound is a mixture of 5-chloro-2-methyl-4- isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in the weight ratio of 50:50 - 99:1. 4. The stabilized isothiazolone composition according to claim 1 , wherein the isothiazolone composition comprises 0.1 - 40 wt % of one or more compounds selected from isothiazolone represented by formula 1 , 0.1 - 99 wt % of stabilizer, and 99.8 wt % or less of solvent. 5. A method of stabilization of isothiazolone comprising stabilizing isothiazolone by blending isothiazolone and a stabilizer, wherein said isothiazolone is the compound represented by the formula 1 , the stabilizer is sulfuric acid [formula 1] Wherein R 1 and R 2 , which are the same or different, respectively represent a hydrogen atom; a halogen atom; or C, - C 4 alkyl group; or R 1 and R 2 together form cyclic allyl group; 5 R 3 represents a hydrogen atom; C 1 ~ C 10 alkyl group which is substituted or unsubstituted with a halogen atom or hydroxy group; C 2 - C 10 alkenyl group which is substituted or unsubstituted with a halogen atom; C 2 - C 10 alkynyl group which is substituted or unsubstituted with a halogen atom; C, ~ C 10 alkyl group; or aralkyl group which is substituted or unsubstituted 10 with C 2 ~ C 9 alkoxy group. 6. A method of stabilization of isothiazolone according to claim 5, wherein the isothiazolone compound is selected from the group consisting of 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, 4,5- dichloro-2-methyl-4-isothiazolin-3-one, 5-chloro-2-n-octyl-4-isothiazolin-3-one, 15 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, benzoisothiazolin-3-one and the mixture thereof. 7. A method of stabilization of isothiazolone according to claim 5, wherein the isothiazolone compound is a mixture of 5-chloro-2-methyl-4- isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in the weight ratio of 20 50:50 - 99:1. 8. A method of stabilization of isothiazolone according to claim 5, wherein the amount of the sulfuric acid is 0.01 ~ 1000 part by weight on the basis of the weight of isothiazolone compound. 9. A method of sterilization of bacteria and/or fungi and/or algae or suppression of the growth thereof comprising applying disinfectant compositions in the area that is contaminated or contamination-vulnerable by bacteria and/or fungi and/or algae, wherein said disinfectant compositions comprise (a) isothiazolone compound represented by the formula 1 , (b) sulfuric acid and (c) solvent. [formula 1] Wherein, R 1 and R 2 , which are the same or different, respectively represent a hydrogen atom; a halogen atom; or C, - C 4 alkyl group; or R 1 and R 2 together form a cyclic allyl group; R 3 represents a C, - C 10 alkyl group which is substituted or unsubstituted with a hydrogen atom, a halogen atom or hydroxy group; C 2 - C 10 alkenyl group which is substituted or unsubstituted with a halogen atom; C 2 - C 10 alkynyl group which is substituted or unsubstituted with a halogen atom; a halogen atom; C, - C 10 alkyl group; or aralkyl group which is substituted or unsubstituted with C 2 - C 9 alkoxy group.

Inventors: CHOI KI-SEUNG, HA JAE-MIN, HAHN SOON-JONG, KIM JIN-MAN, KIM SEUNG-HWAN, PARK JUNG-HO, CHOI, KI-SEUNG, HA, JAE-MIN, HAHN, SOON-JONG, KIM, JIN-MAN, KIM, SEUNG-HWAN, PARK, JUNG-HO
Applicants: CHOI KI SEUNG, HA JAE MIN, HAHN SOON JONG, KIM GI BAE, KIM JIN MAN, KIM SEUNG HWAN, PARK JUNG HO, SK CHEMICALS, CHOI, KI-SEUNG, HA, JAE-MIN, HAHN, SOON-JONG, KIM, GI-BAE, KIM, JIN-MAN, KIM, SEUNG-HWAN, PARK, JUNG-HO
Application year: 2000
Main classification: A01N43
IPC codes: A01N43