JP4525136B2 - Controlled release algae, Legionella spp. Control agent and composition thereof - Google Patents

Description

  The present invention relates to a control agent for water-based algae and Legionella spp. More specifically, the present invention relates to skin for controlling algae / Legionella genus living in circulating water in cooling towers, circulating cooling water in refrigeration equipment, cold / hot water systems such as hot water pools and bathhouses, and heat storage water systems. The present invention relates to a sustained-release algae and Legionella control agent having improved irritation and a composition thereof.

Technical background

  In recent years, the problem of legionellosis due to Legionella spp. Living in open circulation system cooling water such as air-conditioning equipment has frequently occurred. If these cooling towers are close to the window of the living room or the outside air intake of the air conditioner, the aerosol of cooling water enters the room and causes legionellosis. Especially during the summer season when air conditioning is necessary, the water temperature in the cooling tower rises (approximately 15 ° C to 35 ° C), and organic substances are concentrated in the tower. Or a place suitable for the growth of microorganisms and pathogens. In addition, biofilms and slime from microorganisms and algae adhere to the pipes, causing deterioration of the heat exchange efficiency of the heat exchanger and clogging of the filter, and pathogenic bacteria, especially Legionella spp. When scattered, it causes special pneumonia, for example, illnesses such as veterans' disease and Pontiac fever. As a countermeasure against such problems caused by algae and microorganisms, a method of suppressing the growth of algae, microorganisms and bacteria by injecting antialgae and antibacterial agents into the circulating water system, etc. A chemical cleaning method using a cleaning agent has been used.

  As a method of injecting antibacterial agents to inhibit the growth of bacteria, halogen antibacterial agents such as chlorine, bromine and chlorine dioxide, surfactants such as quaternary ammonium salts, hydrazines and maleimides, isothiazoline compounds, Organic compounds such as phosphonium compounds and nitroalcohol compounds are mainly used. However, the halogen compound has a problem that it easily corrodes equipment and piping, and the organic compound has a problem of toxicity such as skin irritation, sensitization, and carcinogenicity and insufficient efficacy. In addition, there are also problems that it is necessary to use many drugs from the viewpoint of efficacy and sustainability, and the environmental load is large. In order to suppress proliferation as a method for solving these problems, it is necessary to continuously add anti-algae / antibacterial agents or to add them at regular time intervals (see, for example, Patent Documents 1 and 2). .

  In Japanese Patent Publication No. 57-42603, the dithiol antibacterial agent represented by the general formula (I) is known to have high antibacterial activity, and is generally used mainly as a slime control agent for papermaking ( For example, see Patent Document 3.) This compound, like other organic compounds, is toxic, such as skin irritation, or under alkaline conditions or in the presence of reducing substances or nucleophiles (sulfides, amines, etc.). There was a problem that it was easily disassembled. In order to solve these problems, WO02 / 089578 discloses a method for microencapsulating the antibacterial agent. However, it was not known to be effective for removing Legionella (see, for example, Patent Document 4).

  In addition, dithiols are highly irritating to the skin, and when handled as a powder, there are problems such as rashes and blisters when coming into contact with the skin due to powdering, which makes it difficult to develop as a solid preparation. It was. Moreover, since it is low in water solubility, when it is used as a water treatment agent, it needs to be dissolved in a hydrophilic solvent, which makes it difficult to formulate as an aqueous solution and difficult to use in open circulating cooling water.

JP-A-5-247011 introduces an inclusion compound of cyclodextrin and isothiazolines, which are generally known as industrial disinfectants, and reports that skin irritation is reduced. However, there is no description about a dithiol compound (for example, refer to Patent Document 5).
JP-A-7-256266 JP 2002-263659 A Japanese Patent Publication No.57-42603 International Publication No. 02/089578 Pamphlet Japanese Patent Laid-Open No. 5-247011

  The present invention aims to control bacteria such as algae and Legionella living in circulating water in cooling towers, circulating cooling water in refrigeration equipment, cold and hot water systems such as hot water pools and bathhouses, and heat storage water systems. In addition, by slow release of dithiols by microencapsulation or inclusion, it is possible to increase the sustainability and reduce toxicity such as skin irritation of dithiols when attached to the skin. is there. Furthermore, since the dithiols used in the present invention are effective at a low concentration, the environmental load is small. Moreover, the control agent and control agent composition of the present invention are also effective against wrinkles.

  As a result of earnest research to solve the above-mentioned problems, the present inventor, against algae and Legionella genus bacteria living in an aqueous system using a dithiol compound encapsulated by microencapsulation or cyclodextrin, It has been found that it has an excellent control effect, and the present invention has been invented based on this finding.

（式中、Ｒ１及びＲ２は、水素原子、又はハロゲン原子を示し、それぞれ同一又は異なっていてもよい。）で表されるジチオール化合物を必須成分とする皮膚刺激性の改善された徐放化藻類及びレジオネラ属菌防除剤、
（２）徐放化がマイクロカプセル化であることを特徴とする請求項１記載の皮膚刺激性が改善された徐放化藻類及びレジオネラ属菌防除剤、
（３）徐放化がシクロデキストリンによる包接化であることを特徴とする請求項１記載の皮膚刺激性が改善された徐放化藻類及びレジオネラ属菌防除剤、
（４）（１）〜（３）のいずれかに記載の防除剤が冷却塔循環水用であることを特徴とする皮膚刺激性が改善された徐放化藻類及びレジオネラ属菌防除剤、
（５）一般式（Ｉ）

（式中、Ｒ１及びＲ２は、水素原子、又はハロゲン原子を示し、それぞれ同一又は異なっていてもよい。）で表されるジチオール化合物を必須成分とする皮膚刺激性の改善された徐放化藻類及びレジオネラ属菌防除剤に腐食防止剤、スケール防止剤、消泡剤及び界面活性剤の少なくとも一種を配合することを特徴とする皮膚刺激性の改善された徐放化藻類及びレジオネラ属菌防除剤組成物、
（６）（５）記載の組成物が冷却塔循環水用であることを特徴とする皮膚刺激性の改善された徐放化藻類及びレジオネラ属菌防除剤組成物、に関する。That is, the present invention
(1) General formula (I)

(Wherein R1 and R2 each represent a hydrogen atom or a halogen atom, which may be the same or different from each other), and a sustained-release alga with improved skin irritation comprising a dithiol compound as an essential component And Legionella control agent,
(2) Sustained release alga and Legionella control agent with improved skin irritation according to claim 1, characterized in that sustained release is microencapsulation,
(3) Sustained release alga and Legionella control agent with improved skin irritation according to claim 1, characterized in that sustained release is inclusion by cyclodextrin,
(4) Controlled release algae and Legionella control agent with improved skin irritation characterized in that the control agent according to any one of (1) to (3) is for cooling tower circulating water,
(5) General formula (I)

(Wherein R1 and R2 each represent a hydrogen atom or a halogen atom, which may be the same or different from each other), and a sustained-release alga with improved skin irritation comprising a dithiol compound as an essential component And a sustained-release alga and Legionella control agent with improved skin irritation, characterized in that at least one of a corrosion inhibitor, a scale inhibitor, an antifoaming agent and a surfactant is added to the Legionella control agent Composition,
(6) The present invention relates to a sustained-release algae and Legionella control agent composition with improved skin irritation, wherein the composition according to (5) is used for cooling tower circulating water.

  According to the method for controlling algae and Legionella in an aqueous system of the present invention, by adding a microcapsule or cyclodextrin inclusion product containing a dithiol antibacterial agent as a main component, circulating cooling water of a refrigeration apparatus, or 24 It is possible to control Legionella spp. Living in cold / hot water systems such as circulating hot water in a time bath, and heat storage water systems, and to prevent their growth. It is also useful as an industrial control agent for spoilage bacteria for metalworking oil, paper industry, paint, textile oil, wood treatment and the like.

  The dithiol-based compound used in the present invention is known as a compound having an excellent action as a slime control agent, and is used in the papermaking process in the papermaking industry.

Examples of the dithiol compound represented by the general formula (I) include 4,5-dichloro-1,2-dithiol-3-one and 1,2-dithiol-3-one , which are used as a mixture. Also good. Of these, 4,5-dichloro-1,2-dithiol-3-one is preferable.
The content of the dithiol-based compound represented by the general formula (I) in the microcapsule or the inclusion product is not particularly limited, and the addition amount is based on the aqueous system in which Legionella spp. The concentration of the dithiol compound is preferably in the range of 0.1 to 100,000 mg / L, more preferably 1 to 100 mg / L.

In the present invention, other antibacterial agents may be used. Antibacterial agents used in combination include surfactant fungicides such as quaternary ammonium salts, hydrazines and maleimides, isothiazoline compounds, phosphonium compounds, bromonitro compounds, pyrithione compounds, etc. N, N-dimethyl-N, N-di-n-decylammonium chloride, N, N-dimethyl-N, N-di-n-octylammonium chloride, N, N-dimethyl-N-octyl-N-decylammonium chloride N, N-dimethyl-N-isononyl-N-decylammonium chloride, N-hexadecyl-N, N, N-trimethylammonium chloride, N-hexadecyl-N, N, N-trimethylammonium bromide, N, N-dimethyl -N-octadecyl-N- (3- (trimethoxylyl) propyl) ammo Um chloride, hydrazine, hydrated hydrazine, hydrazine sorbazine, maleimide, N-methylmaleimide, N-ethylmaleimide, citraconic imide, N-methylcitraconic imide, N-ethylcitraconic imide, 2,3-dimethylmaleic imide N-methyl-2,3-dimethylmaleimide, N-ethyl-2,3-dimethylmaleimide, N- (2-hydroxyethyl) maleimide, N-cyclohexylmaleimide, N-4-hydroxycyclohexylmaleimide, N-phenylmaleimide, Np-hydroxyphenylmaleimide, Np-hydroxybenzylmaleimide, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, 5 -Chloro-2-n-octi Isothiazolin-3-one, 1,2-benzisothiazolin-3-one, tetrakis (hydroxymethyl) phosphonium sulfate, tetrakis (hydroxymethyl) phosphonium phosphate, tetrakis (hydroxymethyl) phosphonium nitrate, tetrakis (hydroxymethyl) phosphonium Hydrochloride, tetrakis (hydroxymethyl) phosphonium bromide, tetrakis (hydroxymethyl) phosphonium hydrofluorate, 2-bromo-2-nitropropane-1,3-diol, 2,2-dibromo-2-nitropropane-1 -Ethanol, 2,2-dibromo-3-nitropropionamide, bis (2-pyridinethiol-1-oxide) copper salt, bis (2-pyridinethiol-1-oxide) zinc salt, bis (2-pyridinethiol- 1-oxide) iron salt, 2-pyridylthio-1-oxide sodium, pyrithione disulfide, glutaraldehyde, hydrogen peroxide, 1-bromo-3-chloro-5,5-dimethylhydantoin, methylenebisthiocyanate, sodium hypochlorite, 1,5-pentanedi Are, 3- (3,4-dichlorophenyl) -1,1-diphosphonic acid, 2,3,3-triiodoallyl alcohol, especially 2,2-dibromo-3-nitropropionamide, 2-bromo-2-nitro Propane-1,3-diol, 5-chloro-2-methyl-4-isothiazolin-3-one, and 2-methyl-4-isothiazolin-3-one are preferred.
These bactericidal / antibacterial agents can be used alone or in combination with a dithiol compound, and the blending amount thereof preferably does not exceed the blending amount of the dithiol compound.

  The sterilizing / antibacterial agent that can be used in combination can be used in combination with a microcapsulated or encapsulated dithiol compound. In addition, halogen antibacterial agents such as chlorine, bromine and chlorine dioxide can be used in combination as long as they are microencapsulated or included with cyclodextrin and do not inhibit the antibacterial activity of the dithiol compound.

  Polymer compounds that form the wall agent used in microencapsulation are polymer compounds such as polyamide resin, saturated / unsaturated polyester resin, epoxy resin, urethane resin, silicone resin, melamine resin, gelatin, urea resin, phenol resin, etc. Or a polymer composed of a mixture of these may be used without any particular limitation. Of these, melamine resin, urethane resin, and polyamide resin are preferable, and melamine resin is particularly preferable.

  The microencapsulation method can be performed, for example, by the following method. That is, in order to prepare microcapsules using the dithiol compound of the present invention as a core material, for example, a core material is covered with a water-soluble polymer such as gelatin, and a wall film is formed so as to separate and harden the concentrated phase. Cellulation method, interfacial degeneracy in which a monomer is planted in a core material in a dispersed state, and a water-soluble monomer in a solution that forms a continuous phase is polymerized at the interface to form a wall film containing the core material. legal. In addition, any known microencapsulation method such as an in-situ polymerization method in which a polymerization catalyst is adsorbed on the core substance and reacted to surround the initial polycondensate from the outside to form a wall film may be used. Is not to be done.

  The inclusion control agent by cyclodextrin in the present invention refers to dithiol compounds represented by the general formula (I) as cyclodextrins, that is, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, methyl-α. -Inclusion with cyclodextrins such as cyclodextrin, methyl-β-cyclodextrin, methyl-γ-cyclodextrin, hydroxypropyl-α-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxypropyl-γ-cyclodextrin, etc. Say something.

  The inclusion method can be performed, for example, by the following method, but is not particularly limited.

<Saturated aqueous solution method>
When the dithiol compound is added to a saturated aqueous solution of cyclodextrin as it is or dissolved in a small amount of a suitable solvent, and the mixture is vigorously mixed and stirred for 0.5 hours to several hours, the clathrate of the present invention is precipitated as a solid. When this is filtered and dried, the inclusion product of the present invention is obtained as a powder.

<Kneading method>
Add 0.3 to 3 times the amount of water to cyclodextrin and knead to prepare a slurry. When the dithiol compound is added as it is or dissolved in a small amount of an appropriate solvent and kneaded for 0.5 to several hours, the inclusion product of the present invention is obtained.

  In the inclusion product of the present invention, since the dithiol compound, which is a control active ingredient, does not elute as it is, it may be used as a powder control agent because the skin irritation is weakened even if it adheres. Or processed into a solid form such as a tablet or a tablet.

  Examples of the corrosion inhibitor in the composition of the present invention include monoethanolamine, diethanolamine, triethanolamine, 1,2,3-benzotriazole, and alkylbenzotriazole.

  Examples of the scale inhibitor include styrene sulfonic acid soda, sulfonic acid group-containing polymer, 1,4-naphthoquinone, 1,2-naphthoquinone, benzoquinone, phosphonate, orthophosphate, polyphosphate, and the like.

  Examples of antifoaming agents include dimethyl silicone oil, alkyl aralkyl-modified silicone oil, fluorosilicone oil, glycerin fatty acid ester, lecithin and the like.

  Surfactants include anionic surfactants such as alkylbenzene sulfonates and alkyl ether sulfates, cationic surfactants such as aliphatic quaternary ammonium salts, benzaconium chloride and pyridinium salts, carboxybetaines, and aminocarboxylic acids. Nonionic surfactants such as salt, imidazolium betaine, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, etc. Can be mentioned.

  Examples of the method for applying the control agent composition of the present invention to the target aqueous system include, for example, adding the control composition directly to the aqueous system, charging, mixing, etc. Examples of the method include applying or penetrating an object.

  The control agent of the present invention controls bacteria such as Legionella spp. That live in chilled and warm water systems such as circulating cooling water in refrigeration equipment, circulating hot water in baths for 24 hours, and heat storage water systems. Can be prevented.

The content of the dithiol compound represented by formula (I) in the microencapsulation or inclusion control agent is not particularly limited as long as it is a content necessary for achieving the object of the present invention.
The concentration of the dithiol compound is preferably in the range of 0.1 to 100,000 mg / L of the dithiol compound relative to the aqueous system in which Legionella spp. / L is more preferable.

  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.

Synthesis example 1
Solution A is prepared by dissolving 40 grams of 4,5-dichloro-1,2-dithiol-3-one in 160 grams of dibutyl adipate. A solution A is added to 300 g of a 2% gelatin aqueous solution and emulsified to prepare an O / W emulsion. The resulting O / W emulsion is brought to pH 8-9 with 10% aqueous sodium carbonate and 80 grams of melamine formaldehyde is added. Next, the pH was adjusted to 5.5 with citric acid, and the mixture was stirred at 70 ° C. for 2 hours to obtain a dithiol-encapsulated microencapsulated preparation (YF-12) having an average particle diameter of 2 microns having a melamine film.

Example 1
(1) Preparation of specimen 200 mL of pure water is put into 6 300 mL Erlenmeyer flasks and autoclaved. Take 10.31 g of YF-12 and make up to 100 mL with pure water (10,000 mg / L as 4,5-dichloro-1,2-dithiol-3-one). This is used as a specimen preparation solution. Add 20 μL, 100 μL, 200 μL, 400 μL, and 600 μL of the sample preparation solution to a sterilized Erlenmeyer flask to prepare a sterilized NaOH or HCL aqueous solution, and adjust the pH to the range of 6.5 to 7.5. The concentration of the test substance including the blank is 0, 1, 5, 10, 20, 30 mg / L.

(2) Preparation of bacterial suspension An appropriate amount of Legionella spp. Is inoculated in advance in a BCYE medium, and cultured to become a fresh culture on the test day. Scatter bacteria from the medium using a platinum loop and suspend in sterile water. After suspended to approximately 10 ⁷ cells / mL, is added to each Erlenmeyer flask by 2 mL. The test begins when the bacteria are added.

(3) Measurement of the number of bacteria After 0, 6, 12, 24, 48 hours from the start of the test, take the test solution, make a 1, 10, 100, 1,000, 10,000-fold dilution series, Take 0.1 mL and smear on WYO medium. Then, in order to avoid drying, it packs in a vinyl bag, inverts, and culture | cultivates at 37 degreeC for 1 week. After completion of the culture, colonies were counted, and the number of viable Legionella that changed with changes in concentration and the number of viable Legionella that changed with time were measured. These results are shown in Table 1.

Example 2
(1) Preparation of specimen 200 mL of pure water is put into 6 300 mL Erlenmeyer flasks and autoclaved. Take 10.31 g of YF-12 and make up to 100 mL with pure water (10,000 mg / L as 4,5-dichloro-1,2-dithiol-3-one). This is used as a specimen preparation solution. Add 20 μL, 50 μL, and 100 μL of the sample preparation solution to the sterilized Erlenmeyer flask to prepare a sterilized NaOH or HCL aqueous solution, and adjust the pH to the range of 6.5 to 7.5. The concentration of the test substance including the blank is 0, 0.1, 0.25, 0.5 mg / L.
(2) Preparation of bacterial suspension An appropriate amount of Legionella spp. Is inoculated in advance in a BCYE medium, and cultured to become a fresh culture on the test day. Scatter bacteria from the medium using a platinum loop and suspend in sterile water. After suspended to approximately 10 ⁷ cells / mL, is added to each Erlenmeyer flask by 2 mL. The test begins when the bacteria are added. 24 hours after the start of the test, the fungus was added again in the same manner in order to confirm the persistence of the effect of the drug.
(3) Measurement of the number of bacteria After 0, 6, 12, 24, 30, 36, 48 hours from the start of the test, take the test solution and make a 1, 10, 100, 1,000, 10,000-fold dilution series Take 0.1 mL of the diluted solution and smear on the WYO medium. Then, in order to avoid drying, it packs in a vinyl bag, inverts, and culture | cultivates at 37 degreeC for 1 week. After completion of the culture, colonies were counted, and the number of viable Legionella that changed with changes in concentration and the number of viable Legionella that changed with time were measured. These results are shown in Table 2.

Comparative Example 1
An aqueous solution containing 10% by weight of 5-chloro-2-methyl-4-isothiazolin-3-one and 4% by weight of 2-methyl-4-isothiazolin-3-one instead of YF-12 (Rohm and Haas) Manufactured, trade name: KATHON WT), the total concentration of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one is 0, 1, 5, 10 , 20, and 30 mg / L. The same operation as in Example 1 was performed. These results are shown in Table 1.

Comparative Example 2
The same operation as in Example 1 was performed except that 2-bromo-2-nitropropane-1,3-diol (trade name: Bronopol, manufactured by Nagase Kasei Co., Ltd.) was used instead of YF-12. These results are shown in Table 1.

Comparative Example 3
An aqueous solution containing 10% by weight of 5-chloro-2-methyl-4-isothiazolin-3-one and 4% by weight of 2-methyl-4-isothiazolin-3-one instead of YF-12 (Rohm and Haas) Product name: KATHON WT), the total concentration of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one is 0, 0.1, 0 The same operation as in Example 2 was performed except that the amount was 0.5 mg / L. These results are shown in Table 2.

From the results in Table 1, when comparing the viable cell count (cells / mL) at the addition concentration of 1 mg / L of each drug shown in Example 1 and Comparative Examples 1 and 2, Example 1 using YF-12 In 6 hours, 4.5 × 10 ³ units / mL, after 12 hours, <10 units / mL, after 24 hours, <10 units / mL, after 48 hours, <10 units / mL On the other hand, in the comparative examples 1 and 2 using a well-known disinfectant, it is a 10 < ⁴ > -10 < ⁵ > piece / mL level. In Table 2, when the addition concentration is 0.5, YF-12 is <10 / mL on the 48th hour after re-inoculation with the bacteria, whereas Comparative Example 3 is a known fungicide. When it is used, the microencapsulated antibacterial agent containing a dithiol compound as a main component has a lower concentration than that of a known disinfectant against Legionella, since it is in the order of 8 × 10 ³ / mL after 48 hours. It turns out that it has the outstanding control power.
Furthermore, in order to confirm the persistence of the fungicide in Table 2, YF-12 has the ability to disinfect even after re-inoculation with bacteria 24 hours later, and the effect of the drug continues even after sterilization. I understand.

Synthesis example 2
Production of inclusion product of cyclodextrin “inclusion compound 1”: β-cyclodextrin (sold by Nippon Food & Chemical Co., Ltd. under the trade name of Celdex B-100) was added water, and the slurry was put in a mortar. Knead until it becomes a shape. Into this, 5 g of 4,5-dichloro-1,2-dithiol-3-one (Microban 86 base material manufactured by API Corporation) is added and then kneaded. After about 20 minutes, the viscosity gradually increases, but when kneading reaches a certain viscosity, kneading is stopped, and drying and pulverization yields the desired clathrate powder.

When the infrared absorption spectrum of this powder was measured, it was confirmed that it was an inclusion compound by the fact that it was not present in β-cyclodextrin and the absorption band peculiar to the dithiol compound was shifted to the high wavenumber side.
Dithiol compound → inclusion dithiol compound: 1516 to 1521 cm ⁻¹ → 1526 to 1531 cm ⁻¹ , 1626 to 1631 cm ⁻¹ → 1680 to 1685 cm ⁻¹ .

Synthesis example 3
Production of inclusion product of cyclodextrin “inclusion compound 2 ”: 2-hydroxypropyl-β-cyclodextrin (sold by Nippon Food Chemical Co., Ltd. under the trade name of Celdex HP-β-CD) in 30 g of water And knead in a mortar until it becomes a slurry. 4 g of 4,5-dichloro-1,2-dithiol-3-one (Micro Bang 86, manufactured by API Corporation) is added to this, and then kneaded. After about 20 minutes, the viscosity gradually increases, but when kneading reaches a certain viscosity, kneading is stopped, and drying and pulverization yields the desired clathrate powder.

  As in Synthesis Example 2, this powder was also confirmed to be an inclusion compound by shifting the specific absorption band of the dithiol compound in the infrared absorption spectrum toward the high wavenumber side.

に示す。Example 3
Six 300 mL containers containing 200 mL of pure water are sterilized by autoclaving, and then “inclusion compound 1” is added to a final concentration of 0, 1, 5, 10, 20, and 30 mg / L. Take freshly cultured Legionella spp., Adjust to pure water to about 10 ⁷ cells / mL, add 10 mL to each container, and finally adjust to about 10 ⁵ cells / mL. Mix occasionally, and after 0, 6, 12, 24, and 48 hours, remove the liquid, create several 10-fold dilution series, inoculate in WYOα medium, culture at 37 ° C for 1 week, and count the emerged colonies Then, the number of viable Legionella that changed with changes in concentration or the number of viable Legionella that changed with time was observed. These results

Shown in

Comparative Example 4
In place of “inclusion compound 1”, an aqueous solution containing 10% by weight of 5-chloro-2-methyl-4-isothiazolin-3-one and 4% by weight of 2-methyl-4-isothiazolin-3-one [Rohm and Haas, KATHON WT], the total concentration of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one is 0, 1, 5, 10, The same operation as in Example 3 was performed, except that the concentration was 20, 30 mg / L. These results are shown in Table 3.

Comparative Example 5
The same operation as in Example 3 was performed, except that 2-bromo-2-nitropropane-1,3-diol [generic name: bronopol] was used instead of “clathrate compound 1”. These results are shown in Table 3.

Table 3

As can be seen from Table 3, when the number of viable bacteria was compared at an addition concentration of 1 mg / L for each drug, 4.5 × 10 ³ cells were obtained after 6 hours in Example 3 using “inclusion compound 1”. / mL stand, a <10 ² cells / mL stand after 12 hours, a <10 ² cells / mL stand after 24 hours, and <10 ² cells / mL stand after 48 hours, a known fungicide In Comparative Examples 1 and 2 used, since the number is 10 ⁵ / mL, the control agent including the dithiol compound may have a control power superior to that of a known fungicide against Legionella. I understand.

Example 4
(1) Preparation of specimen 200 mL of pure water is put into 6 300 mL Erlenmeyer flasks and autoclaved. 379 mg of inclusion compound 2 is taken and made up to 100 mL with pure water. This is used as a specimen preparation solution. Add 20 μL, 100 μL, 200 μL, 400 μL, and 600 μL of the sample preparation solution to the sterilized Erlenmeyer flask to prepare a sterilized NaOH or HCL aqueous solution, and adjust the pH to the range of 7.0. The concentration of the test substance including the blank is 0, 1, 5, 10, 20, 30 mg / L.
(2) Preparation of bacterial suspension An appropriate amount of Legionella spp. Is inoculated in advance in a BCYE medium, and cultured to become a fresh culture on the test day. Scatter bacteria from the medium using a platinum loop and suspend in sterile water. After suspended to approximately 10 ⁷ cells / mL, is added to each Erlenmeyer flask by 2 mL. The test begins when the bacteria are added.
(3) Measurement of the number of bacteria After 0, 6, 12, 24, 48 hours from the start of the test, take the test solution, make a 1, 10, 100, 1,000, 10,000-fold dilution series, Take 0.1 mL and smear on WYO medium. Then, in order to avoid drying, it is packed in a vinyl bag, inverted, and cultured at 37 ° C. for 1 week. After completion of the culture, colonies were counted, and the number of viable Legionella that changed with changes in concentration and the number of viable Legionella that changed with time were measured. These results are shown in Table 4.

Example 5
The same operation as in Example 4 was performed except that the pH was changed to 8. These results are shown in Table 4.

Comparative Example 6
Instead of inclusion compound 2, an aqueous solution containing 10% by weight of 5-chloro-2-methyl-4-isothiazolin-3-one and 4% by weight of 2-methyl-4-isothiazolin-3-one (Rohm and Haas) The total concentration of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one is 0, 1, 5, The same operation as in Example 4 was performed except that the doses were 10, 20, and 30 mg / L. These results are shown in Table 4.

Comparative Example 7
The same operation as in Example 4 was carried out except that 2-bromo-2-nitropropane-1,3-diol (trade name: Bronopol, manufactured by Nagase Kasei Co., Ltd.) was used instead of the inclusion compound 2. These results are shown in Table 4.

Reference example 1
When an attempt was made in the same manner as in Example 4 using 4,5-dichloro-1,2-dithiol-3-one (non-inclusion) instead of inclusion compound 2, precipitation occurred. The number of viable Legionella that changes over time could not be measured.

From the results shown in Table 4, the number of viable bacteria (cells / mL) at an addition concentration of 1 mg / L for each drug shown in the Examples and Comparative Examples is compared. In Example 4 using the inclusion compound 2, 3 hours whereas becomes later <less than 10 cells / mL, since it is ¹⁰ 3 to 10 ⁶ cells / mL stand in Comparative examples 6 and 7 using a known fungicide, a dithiol compound was clathration It can be seen that the control agent is effective against Legionella bacteria at a lower concentration than known disinfectants, and has excellent sterilization power. Furthermore, from the results of Example 5, it can be seen that even at alkaline conditions such as pH 8, fast effect is observed at a low concentration, and the controllability is excellent in sustainability.

Example 6
A certain amount of inclusion compound 2 was dissolved in Detmer medium containing 10 ⁵ / mL of freshwater algae (Cyanophyceae; Oscillatoria laetevirens), and 4,5-dichloro-1,2-dithiol-3-one in the medium was dissolved. Samples having concentrations of 1 ppm, 10 ppm, 20 ppm, and 30 ppm were prepared, and cultured with shaking by shaking continuously at 20 ° C. for 24 hours. One week later, it was judged visually. The results are shown in Table 5.

Example 7
A certain amount of Compound 2 was dissolved in MIN medium containing 10 ⁵ / ml of freshwater algae (green algae; Graesiella emersonii, formerly Chlorella pyrenoidosa), and 4,5-dichloro-1,2-dithiol-3-one in the medium was dissolved. Samples having a concentration of 1 ppm, 10 ppm, 20 ppm, and 30 ppm were prepared, and cultured with shaking at 23 ° C. for 24 hours. One week later, it was judged visually. The results are shown in Table 5.

Example 8
A certain amount of inclusion compound 2 was dissolved in a MIN medium containing 10 ⁵ / mL of freshwater algae (diatom; Nitzschia closterium), and 4,5-dichloro-1,2-dithiol-3-one in the medium was dissolved. Samples having concentrations of 1 ppm, 10 ppm, 20 ppm, and 30 ppm were prepared, and cultured with shaking at 22 ° C. for 24 hours. One week later, it was judged visually. The results are shown in Table 5.

  The numbers in the table represent the color tone, with 4 being the darkest, 1 being faintly colored, and 0 indicating no change at all.

Example 9
Water Solubility Test The solubility of inclusion compound 1, inclusion compound 2 and 4,5-dichloro-1,2-dithiol-3-one (RYH-86) in water at room temperature was about 8 g / L, respectively. From about 19 g / L and about 0.05 g / L, it is clear that the cyclodextrin inclusion control agent can be solubilized in water 10 times or more because it contains 10% by weight of the active ingredient RYH-86. It was shown that it can be processed as a water-soluble preparation.

Example 10
Example of microencapsulated algae and Legionella control agent composition Microencapsulated preparation (YF-12) 95% by weight
Diethanolamine (corrosion inhibitor) 3% by weight
Dimethyl silicone oil <Antifoaming agent> 2% by weight
When only the microencapsulated preparation was added to the cooling tower circulating water, foaming occurred during use, but foaming was not observed in the present composition containing dimethyl silicone oil.

Example 11
Example of Inclusion Algae and Legionella Control Agent Composition Inclusion Compound 1 96% by weight
Benzotriazole (corrosion inhibitor) 2% by weight
Sodium alkylbenzene sulfonate 2% by weight
Compared with the case where only the clathrate compound was dissolved in water, a uniform dissolved product was obtained.

  According to the control agent of the present invention and the composition thereof, the toxicity of dithiols such as skin irritation is reduced, the circulating water of the cooling tower, the circulating cooling water of the refrigeration apparatus, the cold / hot water system such as the hot water pool and bathhouse, Bacteria such as algae and Legionella genus living in the heat storage water system can be controlled. Moreover, sustained elution of dithiols is sustained by microencapsulation or inclusion, and the durability of the efficacy is increased. Furthermore, since dithiols are effective at a low concentration, there is little environmental burden. The control agent and control agent composition of the present invention are also effective against wrinkles.

Claims (10)

Formula (I)

(Wherein R1 and R2 each represent a hydrogen atom or a halogen atom, and may be the same or different from each other). Sustained-release algae and Legionella control agents with improved properties.   A controlled-release alga and Legionella control agent with improved skin irritation, characterized in that the control agent according to claim 1 is for cooling tower circulating water. Formula (I)

(Wherein R1 and R2 each represent a hydrogen atom or a halogen atom, and may be the same or different from each other). Slowly improved skin irritation characterized by blending at least one of a corrosion inhibitor, a scale inhibitor, an antifoaming agent and a surfactant with a controlled release alga and Legionella sp. Release algae and Legionella bacteria control agent composition.   4. The sustained release algae and Legionella control agent composition with improved skin irritation, characterized in that the composition according to claim 3 is for cooling tower circulating water. Cyclodextrin is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, methyl-α-cyclodextrin, methyl-β-cyclodextrin, methyl-γ-cyclodextrin, hydroxypropyl-α-cyclodextrin, hydroxypropyl 3. The controlled release alga and Legionella control agent with improved skin irritation according to claim 1 or 2 , which is -β-cyclodextrin or hydroxypropyl-γ-cyclodextrin . Dithiol compound, 4,5-dichloro-1,2-dithiol-3-one characterized in that it is a claim 1, 2 and any sustained release with improved skin irritation according to one of 5 Algae and Legionella spp . Cyclodextrin is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, methyl-α-cyclodextrin, methyl-β-cyclodextrin, methyl-γ-cyclodextrin, hydroxypropyl-α-cyclodextrin, hydroxypropyl 5. The sustained-release alga and Legionella control composition with improved skin irritation according to claim 3 or 4, which is -β-cyclodextrin or hydroxypropyl-γ-cyclodextrin. The sustained release with improved skin irritation according to any one of claims 3, 4, and 7, wherein the dithiol compound is 4,5-dichloro-1,2-dithiol-3-one. Chemical composition of algae and Legionella spp. The skin irritation according to claim 1 is improved so that the concentration of the dithiol compound is in the range of 0.1 to 100,000 mg / L with respect to an aqueous system in which at least one of Legionella and algae is alive. A method for controlling algae or Legionella, which comprises adding a sustained-release algae and a Legionella control agent . The skin irritation according to claim 3 is improved so that the concentration of the dithiol compound is in a range of 0.1 to 100,000 mg / L with respect to an aqueous system in which at least one of Legionella and algae is alive. A method for controlling algae or Legionella, comprising adding a sustained release algae and Legionella control composition.