JPH01311006A - Industrial antimicrobial and antifungal agent - Google Patents

Abstract

PURPOSE:To obtain the subject agent, containing two or more kinds of 4- isothiazolin-3-one compounds having alkyl groups with different number of carbon atoms, capable of exhibiting excellent antimicrobial activity against bacteria, molds, etc., in a low concentration and effective in using for various industrial raw materials and products, etc. CONSTITUTION:An industrial antimicrobial and antifungal agent containing respectively one or more selected from group (A) 4-isothiazolin-3-one compounds expressed by the formula (R is 1-3C group), e.g., 2-methyl-4-isothiazolin-3-one, and group (B) the 4-isothiazolin-3-one compounds expressed by the formula (R is 4-12C group), e.g., 2-n-butyl-4-isothiazolin-3-one, in the 4-isothiazolin-3-one compounds expressed by the formula (R is 1-12C alkyl or cycloalkyl group; X and Y are H or halogen) which are well-known substances as active ingredients at (1/10)-(10/1) weight ratio of the compounds of the groups (A) to (B). The amount of the above-mentioned agent is 1-3000ppm and mixed in or sprayed on industrial products and raw materials therefor to kill bacteria, molds, etc., or prevent propagation thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to an industrial antibacterial and fungicidal agent effective for various industrial raw materials and products.

(Prior Art) In recent years, microbial damage caused by bacteria, fungi, etc. has frequently occurred in various industrial products and their raw materials, and this has become a problem. This significantly deteriorates the performance, quality, etc. of various industrial products, and a wide variety of fungicides and fungicides are in practical use as preventive measures.

Conventionally, metal compounds such as organic mercury compounds and organic tin compounds, or quaternary ammonium compounds have been used as antibacterial and fungicides in the industrial field mentioned above, but metal compounds are toxic. It is no longer used due to its high level of environmental pollution, which not only affects the human body but also affects fish and shellfish when discharged into rivers. Furthermore, the quaternary ammonium compound was in an undesirable state of foaming during use.

For these reasons, safe and easy-to-use antibacterial and fungicides are desired, such as 1.4-bis(bromoacetoxy)=2-butene, 1.2-bis(bromoacetoxy)ethane, and bis(tribromomethyl). Halogenated compounds such as sulfone, dibromocyanoacetamide, thiocyanate compounds such as methylene bisthiocyanate, 2-(4°-
thiazolyl)-benzimidazole, 1,2-benzisothiazolin-3-one, 4-isothiazolin-3-
Heterocyclic compounds such as on compounds have been developed and are now well known.

(Problem to be Solved by the Invention) However, although the above antibacterial and fungicidal agents are effective against specific microorganisms, they can be used against a wide range of microorganisms, especially bacteria and molds, with a single agent. A wide range of antibacterial activity that can be inhibited cannot be expected, so if the target microorganism is not a single type, or if there are bacteria, molds, yeasts, etc. on which a certain drug does not work effectively, Multiple types of fungicides must be combined and used. In actual industrial raw materials and products, multiple types of microorganisms, multiple types of fungi, molds, and yeasts can grow, so a single drug can inhibit a wide range of antibacterial effects, especially bacteria. There are high expectations for an excellent antibacterial and fungicidal agent that has both the effects of an antibacterial agent that inhibits fungi and a fungicide that inhibits mold.

The present invention meets the above needs and provides an antibacterial and fungicidal agent having a wide range of antibacterial effects.

[Means to solve the problem]

According to the present invention, a 4-isothiazolin-3-one compound represented by Among them, the group of compounds in which R has 1 to 3 carbon atoms is group A, and the group of compounds in which R has 4 carbon atoms is
- If the 12 compound groups are group B, by containing one or more of each of groups A and B as active ingredients, it becomes possible to give a single drug a wide range of antibacterial effects. It can be used as a very wide range of antimicrobial agents that can simultaneously inhibit the growth of bacteria, molds, and yeasts, and are particularly effective against some bacteria and molds.

4-isothiazoline-3- represented by the surface formula (I)
The on compound is a well-known substance, and it is said that in the formula, if the number of carbon atoms in R is small, it shows an inhibitory effect on bacteria, and if the number of carbon atoms in R is large, it shows an inhibitory effect on molds. However, as a result of intensive research, the inventors found that the combination of a compound group in which R has 1 to 3 carbon atoms and a compound group in which R has 4 to 12 carbon atoms has the most significant suppressive effect. Moreover, according to the combination, the effect is synergistic depending on the type of microorganism, and is not just an additive effect.

The reason for this is not entirely clear, but it is thought that in some way, even substances that are weakly effective when used alone can interact with microbial cells by acting together with substances that are strongly effective.

Examples of the compound A group in which R has 1 to 3 carbon atoms and the compound B group in which R has 4 to 12 carbon atoms include the following compounds.

Group A: 2-methyl-4-isothiazolin-3-one 5-
Chloro-2-methyl-4-inthiazolin-3-one 2-ethyl-4-isothiazolin-3-one 5-chloro-2-ethyl-4-isothiazolin-3-one Group B: 2-n-butyl-4 -isothiazolin-3-one 2-t-butyl-4-inthiazolin-3-one 2-n
-hexyl-4-isothiazolin-3-one 5-chloro-2-n-hexyl-4-isothiazolin-3-one 2-cyclohexyl-4-isothiazolin-3-one 4,5-dichloro-2- Cyclohexyl-4-inthiazolin-3-one 2-n-octyl-4-isothiazolin-3-one 5-
Chloro-2-n-octyl-4-inthiazoline-3-
2-t-octyl-4-inthiazolin-3-one 5-
Chloro-2-t-octyl-4-isothiazoline-3-
Also, when Y in formula (I) is a halogen atom, the antibacterial effect is generally stronger than when Y is a hydrogen atom. For example, 5-
It is well known that chloro-2-methyl-4-inthiazolin-3-one has an antibacterial effect that is 10 times stronger than that of 2-methyl-4-isothiazolin-3-one.

In addition, the mixing ratio of Group A and Group B compounds constituting the drug should be high when used for industrial products or raw materials for which the main purpose is to prevent fungi, and the mixing ratio of Group B compounds should be high to prevent bacterial infections. If the main purpose is to prevent spoilage, it is best to use a high mixing ratio of Group A compounds, but in order to create a synergistic effect with Group A and Group B and have a wide range of antibacterial effects, it is better to use Group A compounds. , one or more compounds from group B, respectively, are added to A.
Q, 1~1O of the compound of group B per 1 part by weight of the compound of group B
It is composed in a ratio of parts by weight, preferably in a ratio of 0.25 to 4 parts by weight of a compound of group B to 1 part by weight of a compound of group A.

Incidentally, the compounds of Group A and Group B can be produced by a commonly used production method. That is, from 3.3'-dithiodipropionic acid or its ester, the corresponding N, N'
-dialkyl-3,3-dithiodipropionic acid amide. Then, a 2-alkyl-4-isothiazolin-3-one compound intended for halogenation with a halogenating agent can be obtained. In the final step of halogenation, by changing the halogenating agent, the amount used, or the solvent, X and Y in general formula (1) can be replaced with chlorine,
It can be a halogen atom such as bromine or a hydrogen atom.

The drug having the composition described above has a broad antibacterial spectrum. For example, Pseudomonas, Escherichia,
Active in controlling not only Durham-negative bacteria such as Achromobacter and Durham-positive bacteria such as Bacillus and Staphylococcus, but also molds belonging to Aspergillus, Geotrichum, Penicillium, Fusarium, etc. shows. In particular, synergistic effects appear in bacteria of the genus Bacillus and molds of the genus Cunninghamella. Since most microorganisms can be controlled in this way, problems caused by microorganisms can be prevented or eliminated.

When a composition consisting of Group A and Group B compounds is used as a drug, it can be dissolved in an organic solvent or made water-soluble by forming a metal salt complex. That is, since the compounds of Group A and Group B have similar chemical structures, for example, acetone, methyl ethyl ketone, dioxane, alcohols, glycols, ethylene glycol monomethyl ether, ethylene glycol monomethyl ether,
It can be dissolved in the same organic solvents such as dimethyl sulfoxide, dimethyl formamide, methylene chloride, chloroform, toluene, etc. It also forms metal salt complexes with magnesium chloride, calcium chloride, zinc chloride, magnesium nitrate, or zinc acetate, making it water-soluble. It is also possible to do this. However, when forming these water-soluble metal salt complexes, the content of active ingredients is regulated during actual production, making it difficult to obtain highly concentrated products. On the other hand, those that do not form metal salt complexes are very easily soluble in the organic solvents, can provide highly concentrated products, and are convenient and economical for transportation, storage, handling, etc. Among the organic solvents, hydrophilic solvents are preferred. Glycols and their ethers or alcohols are particularly preferred, and a mixture of them may be used. As glycols, for example, ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, etc. are commonly used, and the stability of Group A and Group B compounds is also good.

Further, ethers or alcohols thereof may also be used.

In addition, when actually using the obtained drug, if it does not form a metal salt complex, for example, when added to latex, it does not cause shock or coagulation, so it may cause quality deterioration or manufacturing problems. It can be prevented. Furthermore, since the solubility in water is lower than that of metal salt complexes, when it is incorporated into an underwater antifouling paint, for example, its antifouling effect can be maintained for a long period of time. Also, since it does not contain water, it is suitable for oil-based paints, etc. On the other hand, when a metal salt complex is formed, the solubility in water is high, so that it can be used, for example, to add sulfur to white water during paper manufacturing.

When using the pharmaceutical composition of the present invention as an industrial raw material or a fungicide, it is generally mixed or sprayed into industrial products and their raw materials in a range of 1 to 3000 ppm to kill or multiply bacteria, mold, etc. can be prevented. For example, 1 to 3 OOOPPM as a fungicide for leather and textile fabrics, 1 to 3000 ppm as a slime control agent in the paper manufacturing process, 1 to 2000 ppm as a preservative for metal processing oil, and 5 to 300 ppm (Ippm, etc.) as a preservative for paints. It goes without saying that formulations that do not contain water are suitable if they do not form a metal salt complex, and formulations that contain water can also be created. When it forms a salt complex, it is suitable for formulations containing water.

As described above, the agent of the present invention can be used as various industrial raw materials such as latex, paste, emulsion paint, oil-based paint, organic adhesive, clay, ink, metal processing oil, wood, leather, fiber, and white water used in paper manufacturing. It can also be used as an antibacterial and antifungal agent for products, etc.

Next, the antimicrobial activity of the antibacterial and antifungal agent of the present invention will be shown in the following test examples, but the present invention is not limited thereto.

〔Example〕

Example 1 (1) Test bacteria, fungi, and yeasts (2) Test method 5-chloro-2-methyl-4-isothiazolin-3-one (AI) and 5-chloro-2-n-octyl- 4-
The antibacterial and fungicidal agent of the present invention, which is a mixture of intiazolin-3-one (BI) in a ratio of 1=1, and the above compounds AI and B
After pouring 10 m of bouillon agar medium (bacteria) and potato agar medium (mold, yeast) containing each of I alone at a predetermined concentration into a vetri dish and solidifying, add 1 platinum loop of the precultured suspension of the test bacteria. Inoculate in streaks,
Molds and yeasts were left in a thermostat at 28°C for 5 days, and bacteria were left at 37°C for 2 days, and the state of bacterial growth was observed.

(3) Test results The minimum inhibitory concentrations are shown in Table 1.

The synergistic effect of the mixture of the present invention is determined by calculating the minimum inhibitory concentration when compound AI and BI are mixed, assuming that the effect of the compound is proportional to the concentration, and from the calculated value obtained, the actual When the same concentration of the mixture is small, it is considered synergistic.

5-chloro-2-methyl-4-isothiazolin-3-one (AI) and 5-chloro-2-n-octyl-
4-Isothiazolin-3-one (BI) alone showed strong antibacterial activity only against bacteria or fungi, and when applied alone to all test bacteria, there was considerable variation in effectiveness; When used in a 1:1 mixture, there was little variation in effectiveness and showed strong antibacterial activity against all microbial groups, including bacteria, molds, and yeasts. In addition, the synergistic effect is particularly strong in bacteria of the genus Bacillus A and molds of the genus Cunninghamella, and in addition, there are also bacteria of the genus E, G, H.
,L was also observed.

Examples 2 to 4 In the same manner as in Example 1, antibacterial tests were conducted with other drugs of the present invention, and the minimum inhibitory concentrations of each were investigated. As shown in Table 2, the results showed that Similar to the result,
The drug of the present invention exhibited strong antibacterial activity against all microbial groups including bacteria, molds, and yeasts.

Example 5 A rot prevention test was conducted on starch starch paste.

Starch paste (30 g of flour and 250 mI of water!, 70 g
℃ heating gelatinization preparation for 30 minutes) was placed in a test tube, and 5-chloro-2-methyl-4-isothiazolin-3-one (compound AI) and 2-n-octyl-4
-Isothiazolin-3-one (compound BrV) used alone and a mixture of both compounds in a ratio of 1=1 were added to each concentration and mixed uniformly. Next, 5g of each glue solution was collected, applied on a slide glass, air-dried for 1 day, and then placed in a vetri dish.
This was inoculated with a mixture of 5 types of bacteria described in Example 1 and a mixture of 6 types of fungi suspended in sterile physiological saline, and left in a thermostat at 28°C for 7 days. rear,
The growth status of the bacteria was examined. The results are shown in Table 3.

Table 3 Antifungal biological test results for starch paste Compound AI: 5-chloro-2-methyl=4-isothiazolin-3-one Compound BIV: 2-n-octyl-4-isothiazolin-3-one Excretion All over the test piece Microbial force <J2't+ Slight physical force on 1/3 of the area of the test piece) Development 11 = - No microorganisms observed on the test piece) 5-chloro-2-methyl-4-isothiazo-1-3-
In a 1:1 mixture of 1:1 (compound AI) and 2-n-cutyl-4-isothiazolin-3-one (compound BIV), the concentrations of compound AI and BrV in the mixture are:
/2, the effects of both compounds AI and B were shown at the same concentration, and at 5 ppm they were able to prevent the occurrence of both bacterial and fungal groups.

Example 6 To 100 ml of latex emulsion was added a fixed amount of the suspension of 5 types of bacteria or 6 types of fungi described in Example 1, and 5-chloro-2-methyl-4-inthiazoline- 3-one (compound AI) or 2-n-octyl-4-isothiazolin-3-one (compound BIV
) was added to a specified concentration, and a mixture of both compounds was added to a specified concentration at a ratio of 1:1, and the mixture was left in a thermostat at 28℃ for 4 weeks. The presence or absence of mold growth and the state of mold growth were investigated. The results are shown in Table 4.

Table 4 Latex Emulsion Liquid Anti-Rot and Mildew Test Compound AI: 5-chloro-2-methyl-
4-isothiazolin-3-one compound BTV: 2-n-octyl-4-isothiazolin-3-one 5-chloro-2-methyl-4-isothiazolin-3-one (compound AI) and 2-n-octyl-4-isothiazolin-3-one In the case where 4-isothiazolin-3-one (compound BrV) was blended in a ratio of 1=1, putrefaction and mold growth of the latex emulsion liquid could be completely prevented by adding 10 ppm.

(Effects of the Invention) As explained above, the present invention is capable of treating bacteria, fungi, and other bacteria with a single drug by blending 4-isothiazolin-3-one compounds having two or more persimmons with different numbers of carbon atoms in the alkyl group.
It becomes possible to exhibit antibacterial activity against yeasts at low concentrations. It has great industrial applicability as an antibacterial and antifungal agent for industrial products.

Patent applicant: Ichikawa Synthetic Chemical Co., Ltd.

Claims (2)

[Claims] (1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ Among the 4-isothiazolin-3-one compounds, compounds in which R has 1 to 3 carbon atoms are group A, and R has 4 carbon atoms.
An industrial antibacterial and fungicidal agent, characterized in that, when the compound group No. 12 is group B, it contains one or more types from group A and group B as active ingredients. (2) The industrial antibacterial and fungicidal agent according to claim 1, which contains a compound of group A and a compound of group B as active ingredients in a weight ratio of 1/10 to 10/1.