JPH0780731B2 - Industrial antiseptic and fungicide - Google Patents

Description

TECHNICAL FIELD The present invention relates to an industrial antiseptic and fungicide. More specifically, various industrial raw materials or industrial products such as dyes, sizing agents, wood, leather, fibers, and pulp are used for preventing spoilage by microorganisms such as bacteria and fungi, and deterioration due to mold. The present invention relates to an industrial antiseptic and fungicide.

(B) Conventional Technology Many chemicals such as organic mercury compounds, organic tin compounds and chlorinated phenols have been used as industrial antiseptic and fungicides. However, in recent years, toxicity and environmental pollution of these compounds have become a problem.

The quaternary ammonium compound which is the composition of the present invention and 3-
Iodo-2-propynyl-N-butylcarbamate is
It is known that each of them is a low toxicity antimicrobial agent. However, when used alone, the effect may be insufficient, and further, at practical concentrations, the antibacterial spectrum was narrow and the growth of microorganisms could not be efficiently prevented.

(C) Problems to be Solved by the Invention An object of the present invention is to provide an antiseptic and fungicide which has low toxicity and exhibits antiseptic and antifungal effects at a lower concentration, and which is effective against a wide range of microorganisms. It is in.

(D) Means and Actions for Solving Problems The present inventors came to the idea of combining various low-toxicity antimicrobials from the above viewpoints, and as a result of earnest research, as a result, a group of quaternary ammonium compounds and 3 -Iodo-2-propynyl-
It has been found that the combination with N-butyl carbamate exerts a significant synergistic antimicrobial effect, and also substantially extends the antibacterial spectrum.

Thus, the present invention has the following formula: (In the formula, R ₁ is an alkyl group or alkenyl group having 8 to 18 carbon atoms, R ₂ is a lower alkyl group, an alkyl group or alkenyl group having 8 to 18 carbon atoms or an aralkyl group, and R ₃ and R ₄ are each a lower alkyl group. Group, X is a halogen atom), and an industrial preservative containing a quaternary ammonium compound (hereinafter abbreviated as QAC) and 3-iodo-2-propynyl-N-butylcarbamate (hereinafter abbreviated as IPBC) The main point is antifungal agents.

In the above definition in QAC, the lower alkyl group means an alkyl group having 1 to 5 carbon atoms.

A benzyl group and a phenethyl group are suitable as the aralkyl group. On the other hand, examples of the halogen atom include a chlorine atom, a bromine atom, an iodine atom and the like, and a chlorine atom is most suitable.

Specific examples of the above QAC, octyl trimethyl ammonium chloride, decyl trimethyl ammonium chloride, dodecyl trimethyl ammonium chloride,
Hexadecyltrimethylammonium chloride, alkyl (C ₈ ~C ₁₉₎ trimethylammonium halides or stearyl trimethyl ammonium chloride, octyl decyl dimethyl ammonium chloride, dioctyl dimethyl ammonium chloride, didecyl dimethyl ammonium chloride, octyl dodecyl dimethyl ammonium chloride, di hexadecyl dimethyl ammonium chloride, dialkyl (C ₈ -C ₁₈₎ such as dioctadecyl dimethyl ammonium chloride dimethylammonium halides and, dodecyl dimethyl benzyl ammonium chloride, hexadecyl dimethyl benzyl ammonium chloride, octadecyl dimethyl benzyl ammonium chloride alkyl chloride such as (C ₈ -C ₁₈₎ benzyldimethyl A Model halide compounds, and the like.
Of course may be these mixtures, mixtures, for example, C ₈ -C ₁₈ alkyl trimethyl ammonium chloride, C ₈ -C ₁₈ dialkyl dimethyl ammonium chloride, C ₈ -C ₁₈ alkyl dimethyl having mixed alkyl groups derived from common fats and oils Benzyl ammonium chloride or the like can be used. Of these, dioctyldimethylammonium chloride, didecyldimethylammonium chloride, dodecyldimethylbenzylammonium chloride, hexadecyldimethylbenzylammonium chloride or octadecyldimethylbenzylammonium chloride is preferably used.

In order to obtain a synergistic effect in the agent of the present invention, it is usually desirable to set the blending ratio (weight ratio) of QAC and IPBC to 1:10 to 30: 1, more preferably, though it depends on the type of bacteria. 2: 1 to 20: 1.

When using the agent of the present invention in the above-mentioned fields of use,
Although it may be used as it is, various dosage forms are conceivable. In general, it is often used as a liquid agent, for example, as a preservative and fungus for starch paste solution, wet pulp, wood and the like. In this case, a solution prepared by dissolving it in an organic solvent may be used, and an emulsion which can be emulsified in water by adding a surfactant if necessary can be prepared. Examples of the organic solvent used here include various organic solvents capable of dissolving both components such as N, N-dimethylformamide, acetone, N-methylpyrrolidone, ethylene glycol monobutyl ether and xylene. Further, as the above-mentioned surfactant, a nonionic surfactant is most suitable, and examples thereof include polyoxyethylene alkylphenyl ether, polyoxyethylene / polyoxypropylene block copolymer, polyoxyethylene alkyl ether, and polyoxyethylene fatty acid ester. Is mentioned. When the target is a powder, it can also be used as a powder, in which case QAC is supported on a carrier such as diatomaceous earth or kaolin, and IPBC
Just mix with. In addition, it is also possible to make a paste with an organic solvent or a surfactant, and the paste can be applied to wood for antiseptic and mildew treatment. Of course, chemicals for other uses such as insecticides may be used together or mixed.

The maximum concentration at which the drug of the present invention is used depends on the target substance and the purpose of use and is not particularly limited. For example, 5 to 100 mg / kg of QAC and 1 to 100 mg / kg of IPBC may be added for antiseptic of a paste solution such as starch paste and mildewproofing of wet pulp. For wood, QAC is 0.1 for fungicides.
˜10 g / m ² and IPBC 0.05 to 1 g / m ² should be absorbed. For the purpose of preserving, QAC should be applied in an amount of 1 to 10 g / m ² and IPBC should be applied in an amount of 0.2 to 5 g / m ² .

(E) Examples The following will describe examples, but the present invention is not limited thereto.

Example: Synergistic effect on microorganisms

(1) Evaluation method The synergistic effect between the two components is measured by the binary dilution method. Both components are diluted to a predetermined concentration and added to the medium in fixed amounts. After inoculating this with a microorganism and culturing under a certain condition, the concentration at which no growth of the microorganism is observed is defined as the minimum inhibitory concentration by the binary dilution method.

FIG. 1 is a graph in which the minimum inhibitory concentration of each component is made equal on both axes using normal scale coordinates. The region on the upper side of the curve of this graph, that is, the TDMIC curve is the growth inhibition region, and the region on the lower side is the growth region. In addition, when the diagonal line and the TDMIC curve match, an additive effect is shown, when there is a curve above the diagonal line, an antagonistic effect is shown, and when below the diagonal line, a synergistic effect is shown.

(2) Synergistic effect on bacteria As a QAC, it is a kind of bacteria that is frequently found in putrefaction products such as latex, starch paste and coating color using didecyldimethylammonium chloride (hereinafter abbreviated as DDAC). Of the genus Bacillus, Bacillus
The synergistic effect on subtilis was determined.

Using broth medium as the medium, inoculate a fixed amount of the bacterial solution precultured overnight, and after shaking culture at 37 ° C for 24 hours,
The concentration at which no turbidity of the medium was observed was determined.

The results are shown in FIG.

As shown in Figure 2, for Bacillus subtilis
The TDMIC curve clearly shows a synergistic effect, and the synergistic effect of the two components that completely suppressed the growth of the bacterium is, for example, DDAC.
Of 1 μg / ml and the concentration of IPBC was 5 μg / ml. DDAC is 4 μg / ml and IPBC is 20 μ when used alone.
Since the growth of bacteria was suppressed at g / ml, the composition of the present invention was 1/4 the amount of each when used alone, showing that a remarkable synergistic effect was exhibited. In addition, examples of combinations of concentrations showing a synergistic effect are as shown in Table 1.

(3) Synergistic effect on molds As DAC is used as QAC as in (2), synergistic effect on Aspergillus niger among Aspergillus species, which is a type of mold that grows well on wet pulp, starch paste, coating color, etc. Was judged.

Using a Tsapeck medium as the medium, 1 spores of spores were collected from the preserved strains that had been previously slope-cultured, inoculated with a fixed amount of the suspension in sterile water, and shake-cultured at 27 ° C for 72 hours. The concentration at which the growth of hypha was not found in the medium was determined.

The results are shown in FIG.

As shown in FIG. 3, the TDMIC curve for Aspergillus niger clearly shows a synergistic effect,
The synergistic effect of the two components that completely suppressed the growth of the bacterium is, for example,
It appeared when the concentration of DDAC was 20 μg / ml and the concentration of IPBC was 0.12 μg / ml. 80 μg / ml for DDAC and 1 for IPBC
Since the growth of bacteria is suppressed at a concentration of μg / ml, the composition of the present invention can be suppressed at 1/4 and 1/8 the amount when used alone, which has a strong synergistic effect. Was shown. Other examples of the combination of the concentrations of DDAC and IPBC showing the synergistic effect are shown in Table 2.

[Example-1 Antiseptic test of starch paste solution] Corn starch was dispersed in water at a weight ratio of 5% and heated to 90 to 95 ° C with stirring to prepare a paste solution. After cooling, 1% of the paste solution which had already spoiled was added, and 100 g was dispensed into a 140 ml glass bottle. DDAC, IPBC and DDAC: IPBC = 1: 1
Each of the above three mixtures was dissolved in N, N-dimethylformamide and added to a predetermined concentration. The cells were cultured at 37 ° C, and the number of bacteria was measured daily.

The results are shown in Table 3.

The numerical values in the table indicate the number of viable bacteria (cells / ml).

As shown in Table 3, the mixture of DDAC: IPBC = 1: 1
The antiseptic effect was clearly superior to that of the single drug at the same concentration, and a synergistic effect was observed.

[Example-2 Antifungal Test of Wet Pulp] Wet pulp (LBKP) is punched out to a diameter of 5 cm to obtain a test piece. Dissolve each of DDAC, IPBC alone and a mixture of DDAC: IPBC = 10: 1 in N, N-dimethylformamide, and evenly spray with a pipette to a predetermined concentration based on the dry weight of pulp. To do. The spray amount was 0.1 ml, and only N, N-dimethylformamide was 0.1 ml as a control.
Prepare the sprinkles. These are left to stand in a Petri dish having a diameter of 9 cm, which is prepared by pouring a medium of the following composition in advance.

Of the fungi that have been separated from the wet pulp in advance and stored, found frequently from the wet pulp, Aspergillus, Penicillium, Trichoderma spores are suspended in sterile water, a certain amount on the sheet Disperse evenly over. The culture was carried out at 27 ° C., and the growth state of the fungus was visually observed daily to determine the effect.

The results are shown in Table 4.

As shown in Table 4, the mixture of DDAC: IPBC = 10: 1 is 2
It was revealed that the addition of 2 mg / kg can completely suppress the development of mold. It was also found that the effect was superior to that of the single drug added at the same concentration as that contained in the mixture, showing a synergistic effect.

[Example-3 Wood antifungal test] A fungicidal test against fungi that grows well on wood was carried out using DDAC and IPBC alone and a mixture of both. The test method was carried out at various concentrations shown in Table 5 in accordance with Standard No. 2 “Test Method for Antifungal Efficacy of Wood Antifungal Agents” established by the Japan Wood Preservation Association (abbreviation JWPA).

(1) Reagents used The drugs used are shown in the table below. The numerical values in the table indicate parts by weight.

(2) Test mold A ₁ Aspergillus niger A ₂ Penicillium funiculosum A ₃ Aureobasidium pullulans A ₄ Gliocladium virens A ₅ Rhizopus javanicus (3) Preparation of test pieces 20 x 3 x 50 mm) 0.03%, 0.06%, 0.12
It is immersed for 3 minutes in the chemical solutions of Formulation Examples 1 to 3 diluted with tap water to 3%. Then, it was air-dried for 2 days to obtain a treated test body.

(4) Mold prevention test Sterilized Petri dishes (90 mm diameter) were autoclaved to 2%
Pour the agar solution and solidify it, and place a polypropylene net on it to form a pedestal so that the test piece does not come into direct contact with the agar.

Three test pieces are placed on a pedestal, and the spore suspension of the test mold is sprinkled on each of them. The number of treated pieces is 6 (1 Petri dish, 2 pieces). The test culture is carried out at 26 ° C. for 4 weeks, and the evaluation is performed according to the criteria shown below by observing the mold growth status of each test piece after 4 weeks for each fungus species and concentration.

Evaluation value Mold growth status 0 No mold growth is observed in the test body.

1 Mold growth is recognized only on the side surface of the test body. 2 Mold growth is recognized in less than 1/3 of the upper surface area of the test body.

3 Mold growth is recognized in more than 1/3 of the upper surface area of the test body.

The damage value (D) in Table 6 is calculated by calculating the sum (S) of the average evaluation values for each concentration of the sample and using the following formula.

Sum of average evaluation values (S) = A ₁ + A ₂ + A ₃ + A ₄ + A ₅ (A ₁ , A ₂ ... A ₅ : average evaluation value for each car type) S ₀ : S of untreated test specimen S S: S of treated specimen with a certain concentration (5) Test results Table 5 shows the results.

The damage value (D) at which a substantial antifungal effect can be expected is 30 or less. According to Table 5, Formulation Example-1 shows the treatment concentration
Even 1.2% (absorption amount 1223 mg / m ² ) exceeds 30. In addition, the formulation example-2 also exceeds 30 at the treatment concentration of 0.6% (absorption amount 510 mg / m ² ). In contrast, Formulation Example-3 has a treatment concentration of 0.3%
Even at (absorption amount of 272 mg / m ² ), it was 30 or less, and it was revealed that it exhibits an excellent antifungal effect and a synergistic effect.

Moreover, Formulation Example-1 (active ingredient DDAC) and Formulation Example-2
(Active ingredient IPBC) has a low fungicidal effect Even against molds A ₄ and A ₅ , Formulation Example 3 (active ingredient DDAC-IPBC), which is an example of the present invention, shows excellent fungicidal effect at low concentrations. ,
It can be seen that the antibacterial spectrum is substantially broadened.

On the other hand, MBTC (methylenebisthiocyanate) or TCMTB [2- (thiocyanomethylthio) benzothiazole], which is a typical antifungal agent on the market, has an antifungal effect against A ₄ fungi alone or in combination. Considering from the fact that it is insufficient, it can be seen that the effect of the present invention has a remarkable effect which is unexpected.

[Example-4 Wood preservative test] DDAC and IPBC alone and a mixture of DDAC: IPBC = 10: 3 were used to perform a preservative efficacy test against various wood-destroying fungi.

The test method was carried out at various concentrations shown in Table 6 in accordance with Standard No. 1 “Test method for preservative efficacy of wood preservatives” established by the Japan Wood Preservation Association (JWPA).

(1) Reagent reagent The same drug as in Example-3 (1) was tested.

(2) Test rot fungus I) Tyromyces palustris II) Coriolus versicolor III) Namitake Serpula lacrymans (3) Preparation of test pieces Three kinds of side wood pieces (5 × 20 of cedar, red pine and beech)
× 40 mm, the surface is the regular one, the mouth end surface is sealed with room temperature curing type epoxy resin), formulation examples 1-3 adjusted to various concentrations of 15, 20 and 25% are 110 ± 10 g / After applying uniformly with a brush so as to be applied at a rate of m ² , and after air-drying, it is divided into two groups, one that does not perform weathering operation and the other that does it. After the latter is treated according to the JWPA weathering operation method, The two groups were dried at 60 ° C. until the sapwood became a constant weight to obtain test pieces.

(4) Antiseptic test and results The culture medium was JIS modified medium (peptone = 0.5%, malt extract =
1%, glucose _{= 2.5%, KH 2 PO 4} = 0.3%, MgSO 4 · 7H 2 O =
0.2%) to cultivate wood-rotting fungus in the culture medium,
Test cultures were carried out by combining the test pieces of the tree species and the wood-destroying fungi as described separately. The preservative efficacy value was determined by setting the culture temperature to 26 ± 2 ° C. for Kawaratake and Amanita mushroom and 20 ± 2 ° C. for Namitake mushroom for a period of 56 days. The results are shown in Table 6. The antiseptic efficacy value was calculated by the following formula.

However, the test wood decay fungi applied to the wood pieces of three tree species are Sugi-Japanese agaricus, Beech-kawaratake,
It was set as Akamatsu-Namitake. When comparing the decay-preventing concentration and decay-preventing absorption amount of wood preservatives, this combination is used to obtain a high preservative efficacy value in a combination that yields a high weight loss with untreated wood. This is a more comprehensive evaluation of the antiseptic effect.

Effectively, the antiseptic efficacy value that can be expected to be 85 is 85.
That is all. As is clear from Table 6, the effective treatment concentration for all combinations of tree species and decay fungi is 25% or more for both Formulation Example-1 and Formulation Example-2, whereas for Formulation Example -3 was not more than 15%, which showed an excellent antiseptic effect, and a remarkable synergistic effect was observed.

(F) Effect of the Invention According to the industrial antiseptic and fungicide of the present invention, an excellent antiseptic and antifungal effect is exhibited by the synergistic antimicrobial action of each active ingredient, whereby microbial damage can be efficiently prevented. ,
Economic efficiency can also be improved. Further, since each active ingredient has low toxicity, it is convenient in terms of environmental pollution.

Therefore, the antiseptic / antifungal agent of the present invention is extremely useful as an industrial antimicrobial agent.

[Brief description of drawings]

FIG. 1 is a graph showing the evaluation criteria of synergistic effect on microorganisms by MIC curve (TDMIC curve) in the two-dimensional dilution method, and FIGS. 2 and 3 are TD of the industrial antiseptic and fungicide of the present invention.
It is a graph which illustrates a MIC curve.

Claims (2)

[Claims] 1. The following formula: (In the formula, R ₁ is an alkyl group or alkenyl group having 8 to 18 carbon atoms, R ₂ is a lower alkyl group, an alkyl group or alkenyl group having 8 to 18 carbon atoms or an aralkyl group, and R ₃ and R ₄ are each a lower alkyl group. Group, X represents a halogen atom) and 3-iodo-
An industrial antiseptic and fungicide containing 2-propynyl-N-butylcarbamate as an active ingredient in a compounding ratio (weight ratio) of 1:10 to 30: 1. 2. The industrial antiseptic and fungicide according to claim 1, wherein the compounding ratio is 2: 1 to 20: 1.