JP2003081713A - Antimicrobial agent composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antimicrobial agent composition which has high safety, high efficacy and a wide antimicrobial spectrum. SOLUTION: This microbial agent composition comprises N,N'- hexamethylenebis(4-carbamoyl-1-decylpyridinium bromide) and at least one of compound selected from the group consisting of the following compounds (a) to (i). (a) 1-[[(3-iodo-2-propynyl)oxy]methoxy]-4-methoxybenzene. (b) 2-n- octyl-4-isothiazolin-3-one, (c) 2-pyridinethiol-1-oxide zinc salt, (d) 2-bromo-2- nitro-1,3-propanediol, (e) 5-chloro-2-methyl-4-isothiazolin-3-one, (f) 2-methyl-4- isothiazolin-3-one, (g) poly(hexamethylenebiguanide) hydrochloride, (h) 4,4- dimethyloxazolidine, and (i) 4-(2-nitrobutyl)morpholine.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an antimicrobial composition useful for industrial use. More specifically, N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and 1-[[(3-iodo-2-
Propinyl) oxy] methoxy] -4-methoxybenzene, 2-n-octyl-4-isothiazolin-3-one, 2-pyridinethiol-1-oxide zinc salt, 2-
Bromo-2-nitro-1,3-propanediol, 5-
Chloro-2-methyl-4-isothiazolin-3-one,
Combined with at least one compound selected from the group consisting of 2-methyl-4-isothiazolin-3-one, poly (hexamethylene biguanide) hydrochloride, 4,4-dimethyloxazolidine, 4- (2-nitrobutyl) morpholine. Thus, it relates to an antimicrobial composition having a synergistic effect of these compounds.

[0002]

2. Description of the Related Art Conventionally, as an antimicrobial agent for industrial water, industrial products or industrial raw materials, inorganic compounds or organic compounds mainly containing heavy metals such as mercury, tin and copper (hereinafter referred to as "heavy metal compounds") have been used. Widely used. However, since these heavy metal compounds are highly toxic,
There is a risk of adversely affecting the human body. Furthermore, the use of heavy metal compounds as antimicrobial agents is not appropriate, as heavy metal compounds can lead to environmental damage.

Many non-metallic antimicrobial agents developed to solve the above problems of heavy metal compounds (for example, organic iodine compounds, nitrile compounds, isothiazolone compounds, benzimidazole compounds, pyrithione compounds). Compounds) are selective in their antibacterial spectrum. Therefore, these non-metallic antimicrobial agents,
Even when applied to industrial water, industrial products or industrial raw materials, especially organic materials (for example, fibers, paints, sizing agents, etc.), these antimicrobial agents do not work, or microorganisms that are difficult to play grow and propagate. , Pollution of industrial water, industrial products, etc., or alteration (eg deterioration) of industrial raw materials occurs. Therefore, depending on the conventional antimicrobial composition,
No satisfactory antimicrobial effect can be obtained.

Therefore, attempts have been made to broaden the antibacterial spectrum and increase the antimicrobial action by combining two or more antimicrobial agents. However, usually, the effect of only one kind of antimicrobial agent is limited to the expression of the effect, or only the arithmetic average effect is obtained.

[0005]

DISCLOSURE OF THE INVENTION The present invention is intended to solve the above problems, and an object of the present invention is to provide an antimicrobial composition having high safety, high efficacy and a broad antibacterial spectrum. It is to be.

[0006]

Means for Solving the Problems The inventors of the present invention have made extensive studies in order to solve the above problems, and as a result, N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and Compounds (a) to (i):
(A) 1-[[(3-iodo-2-propynyl) oxy] methoxy] -4-methoxybenzene, (b) 2-n
-Octyl-4-isothiazolin-3-one, (c) 2
-Pyridinethiol-1-oxide zinc salt, (d) 2-
Bromo-2-nitro-1,3-propanediol,
(E) 5-chloro-2-methyl-4-isothiazoline-
3-one, (f) 2-methyl-4-isothiazoline-3
-One, (g) poly (hexamethylene biguanide) hydrochloride, (h) 4,4-dimethyloxazolidine, and (i) at least one compound selected from the group consisting of 4- (2-nitrobutyl) morpholine. It was found that the combination produces an unexpected synergistic effect. That is, by combining N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) with a compound selected from the group consisting of the compounds (a) to (i) above, each compound alone is used. The inventors have found that an antimicrobial composition having enhanced efficacy and broader antibacterial spectrum than that obtained when used can be obtained, and completed the present invention.

According to the present invention, N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and the following compounds (a) to (i): (a) 1
-[[(3-Iodo-2-propynyl) oxy] methoxy] -4-methoxybenzene, (b) 2-n-octyl-4-isothiazolin-3-one, (c) 2-pyridinethiol-1-oxide. Zinc salt, (d) 2-bromo-2
-Nitro-1,3-propanediol, (e) 5-chloro-2-methyl-4-isothiazolin-3-one,
(F) 2-methyl-4-isothiazolin-3-one,
(G) poly (hexamethylene biguanide) hydrochloride,
(H) 4,4-dimethyloxazolidine, and (i)
An antimicrobial composition containing at least one selected from the group consisting of 4- (2-nitrobutyl) morpholine is provided.

According to the present invention, there is also provided the above composition for inhibiting or killing the growth of bacteria, fungi or algae.

Preferably, the weight ratio of the N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) to the selected compound is 2
It is in the range of 0: 1 to 1:20. More preferably, the above N, N'-hexamethylenebis (4-carbamoyl-
The weight ratio of 1-decylpyridinium bromide) to the selected compound is in the range of 5: 1 to 1: 5.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION As used herein, the term "antimicrobial composition" refers to a composition having the effect of inhibiting the growth of, or killing, microorganisms such as bacteria, fungi and algae. Means a thing. Here, "suppressing microorganisms" means that the composition does not contain an antimicrobial composition,
That is, the degree of growth of the microorganism is less than that of the control, or the microorganism does not grow at all.

A. Composition of Antimicrobial Composition A. 1. Active Ingredient The antimicrobial composition of the present invention comprises N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and the following compounds (a) to (i): (a) 1.
-[[(3-Iodo-2-propynyl) oxy] methoxy] -4-methoxybenzene, (b) 2-n-octyl-4-isothiazolin-3-one, (c) 2-pyridinethiol-1-oxide. Zinc salt, (d) 2-bromo-2
-Nitro-1,3-propanediol, (e) 5-chloro-2-methyl-4-isothiazolin-3-one,
(F) 2-methyl-4-isothiazolin-3-one,
(G) poly (hexamethylene biguanide) hydrochloride,
(H) 4,4-dimethyloxazolidine, and (i)
It contains at least one compound selected from the group consisting of 4- (2-nitrobutyl) morpholine as an active ingredient.

N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) can be synthesized, for example, by the method described in JP-A-9-110692.

1-[[(3-iodo-2-propynyl)
Oxy] methoxy] -4-methoxybenzene can be synthesized, for example, by the method described in Japanese Patent Publication No. 2852289.

2-n-octyl-4-isothiazoline-
3-on is described in, for example, J. Heterocycl. Ch
em. (1971), 8 (4), 571-580.

The 2-pyridinethiol-1-oxide zinc salt can be synthesized, for example, by the method described in US Pat. No. 3,583,999.

2-Bromo-2-nitro-1,3-propanediol can be synthesized, for example, by the method described in JP-B-49-20761.

5-Chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one can be synthesized, for example, by the method described in Japanese Patent Publication 2813383.

Poly (hexamethylene biguanide) hydrochloride can be synthesized, for example, by the method described in British Patent No. 702268.

4,4-Dimethyloxazolidine can be synthesized, for example, by applying the method described in US Pat. No. 2,448,890.

4- (2-nitrobutyl) morpholine is
For example, it can be synthesized by the method described in US Pat. No. 4,088,817.

Proportion of N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) in the antimicrobial composition and a compound selected from the group consisting of compounds (a) to (i). Can be appropriately selected depending on the type of the target microorganism and the conditions under which the composition is used as an antimicrobial agent. Usually N, N'-
The weight ratio of hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) to the compounds (a) to (i) is 20: 1 to 1:20, preferably 5: 1 to 1: 5. , Particularly preferably in the range of 3: 1 to 1: 3.

When a plurality of kinds of the compounds (a) to (i) are used, the above preferable compounding ratio is calculated based on the total weight of them.

The antimicrobial composition of the present invention can be used in a form depending on the purpose of use. For example, the antimicrobial composition of the present invention is simply N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide),
It may be a mixture with a compound selected from the group consisting of the compounds (a) to (i), but preferably N,
In addition to a compound selected from the group consisting of N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and the compounds (a) to (i), a suitable solvent and a dispersant or a carrier or other components are added. May be included.

The total of N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) in the composition of the present invention and a compound selected from the group consisting of the compounds (a) to (i). The content varies depending on the dosage form and the purpose of use, but is usually 0.1% by weight to 95% by weight, preferably 0.2% by weight to 60% by weight, of the entire antimicrobial composition obtained. Is.

The amount of the antimicrobial composition of the present invention to be used varies depending on the composition and the type and concentration of the target microorganisms, but in general, when used in fibers, paints, adhesives, etc. A good effect can be obtained at about 1 mg / kg to 10 g / kg.

A. 2. Solvents and dispersants When the target system is various industrial water systems, considering the solubility and dispersibility of the active ingredient, it is possible to prepare a liquid formulation containing a solvent and a dispersant, as described below. preferable.

As the solvent that can be used in the antimicrobial composition of the present invention, any solvent that does not adversely affect the active ingredient, such as water, alcohols (eg, methyl alcohol, ethyl alcohol, ethylene glycol, propylene glycol) can be used. , Diethylene glycol, glycerin etc.), ketones (eg acetone, methyl ethyl ketone etc.), ethers (eg dioxane, tetrahydrofuran, cellosolve, diethylene glycol dimethyl ether etc.), aliphatic hydrocarbons (eg hexane, kerosene etc.), aromatic Hydrocarbons (eg, benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.), halogenated hydrocarbons (eg, chloroform, carbon tetrachloride, etc.), acid amides (eg, dimethylformamide, etc.) ), Esters (e.g., methyl acetate, ethyl acetate, butyl acetate, fatty acid glycerol ester, etc.), and nitriles (e.g., acetonitrile), and the like.
These solvents may be used alone or in combination of two or more.

The dispersant that can be used in the antimicrobial composition of the present invention includes any dispersant that does not adversely affect the active ingredient, for example, a surfactant. Examples of such surfactants include soaps, sulfuric acid esters of higher alcohols, alkylsulfonic acids, alkylarylsulfonic acids, quaternary ammonium salts, oxyalkylamines,
Fatty acid ester, polyalkylene oxide compound,
Examples thereof include anhydrosorbitol compounds. These dispersants may be used alone or in combination of two or more.

A. 3. Carrier As the carrier that can be used in the antimicrobial composition of the present invention, any carrier that does not adversely affect the active ingredient, for example,
Clays (for example, kaolin, bentonite, acid clay, etc.), talc (for example, talc powder, wax stone powder, etc.),
Examples thereof include silicas (for example, diatomaceous earth, silicic acid anhydride, etc.), alumina, sulfur powder, activated carbon and the like. These carriers may be used alone or in combination of two or more.

A. 4. Other Ingredients The antimicrobial composition of the present invention further comprises other antimicrobial agents (for example, organic chlorine-based germicides, organic phosphorus-based germicides, organic iodine-based germicides, organic sulfur-based germicides, organic nitrogen-based germicides). Agents, organic nitrogen-sulfur fungicides, benzimidazole fungicides, phenolic fungicides, organic acid ester fungicides, antibiotics, etc., insecticides (eg natural insecticides, carbamate insecticides, organophosphorus insecticides) Agents, etc.), auxiliary agents (eg casein, gelatin, starch, alginic acid, agar, C
MC, polyvinyl alcohol, vegetable oil, bentonite,
Cresol soap, etc.), deterioration inhibitor, perfume and the like.

B. Bacteria of interest The antimicrobial composition of the present invention generally acts broadly on bacteria, fungi, algae and the like, and has N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) or ( It has a broader antibacterial spectrum than the antimicrobial composition obtained by formulating the compounds a) to (i) alone. Note that the fungus here is also called a fungus, and includes fungi, yeasts, mushrooms and the like.
The microorganisms which can be stunted or killed by the antimicrobial composition of the present invention include Bacillus.
Us genus, Staphyloco
ccus, Enterobacter (Enterobacter)
ter), Escherichia
Genus, bacteria such as Pseudomonas genus, Aspergillus
Genus, Aureobasidium
m) genus, Chaetomium genus, Cladosporium genus, Gliocladium genus, Penicillium genus, Trichoderma (Tr)
genus ichoderma, Candida
Genus, fungi such as Rhodotorula, genus Chlorella, violet (T
genus rentepohlia, Nostomo
c) genus, algae such as Phormidium genus, and the like.

The antimicrobial composition of the present invention can be applied to various industrial waters, industrial products or industrial raw materials. Such various industrial water, industrial products or industrial raw materials include circulating water, pulp suspension (white water), fibers, paints,
Examples include adhesives, wood, leather, processed paper products, electronic parts, wall coverings, and resin molded products. The present invention is particularly effective when used for organic materials (for example, fibers, paints, sizing agents, etc.).

[0033]

EXAMPLES The following examples further illustrate the antimicrobial efficacy of the antimicrobial composition according to the present invention. The term “MIC” used in this example refers to the minimum inhibitory concentration (ppm) of the active ingredient in the antimicrobial composition. More specifically, N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) in an antimicrobial composition capable of inhibiting the growth of bacteria, fungi or algae, and (a) to It refers to the minimum concentration of a mixture with a compound selected from the compounds of (i).

(Preparation of bacterial solution for inoculation) The bacterial solution for inoculation used in Example 1 was prepared as follows. Two separate normal broth broths (10 ml), two bacteria,
Staphylococcus aureus
occus aureus IFO 12732 and Escherichia co
li) inoculated with IFO 3972 and 4
Two kinds of bacterial solutions for inoculation were prepared by culturing with shaking for about 6 hours.

(Preparation of Spore Suspension for Inoculation) The spore suspension for inoculation used in Example 2 was prepared as follows. Two fungi, Aspergillus niger
gillus niger IFO6341, and Penicillium funiculosum (Penicillium)
funiculosum) IFO 6345 was cultured on two drug-free potato dextrose agar media to form spores. Then add 0.005 of lubricant
The above-mentioned fungal spores were suspended in sterilized water containing 2% to prepare two types of spore suspensions for inoculation.

(Preparation of algae suspension for inoculation) The algae suspension for inoculation used in Example 3 was prepared as follows. B
Chlorella pyrenoida (Chlorella pyren) was added to old's Basal liquid medium (50 ml).
Oidosa) NIES 226 was inoculated at 25 ° C for 1
The culture was carried out with shaking for 4 days to prepare an algal suspension for inoculation.

(Example 1) N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and any of the compounds (a) to (i) were prepared as shown in Tables 1 and 2 below. The antimicrobial composition was prepared by adding dimethylsulfoxide at the weight ratios shown in Table 1 below. Next, each test medium was prepared by adding a serially diluted aqueous solution (0.2 ml) of the antimicrobial composition to a normal broth liquid medium (10 ml). Each test medium was inoculated with the above inoculum bacterial solution (0.1 ml), cultured at 30 ° C. for 24 hours, and the presence or absence of bacterial growth was determined by visually inspecting the turbidity of the medium. Minimum concentration of a mixture of N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and any of the compounds (a) to (i) capable of inhibiting the growth of bacteria in the medium. Is the MIC. The MIC for each bacterium for each weight ratio of the antimicrobial composition is shown in Tables 1 and 2. The concentration of the composition is the sum of the concentration of each antimicrobial agent.
For example, the composition having a 1: 1 mixture of A: a has a minimum inhibitory concentration of 0.2 ppm, but the concentration of A in the composition having this minimum inhibitory concentration is 0.1 ppm, and The concentration is 0.1 ppm.

[0038]

[Table 1] For example, in the case of the composition of A: a = 1: 1 in Table 1,
Assuming no synergistic effect, the minimum inhibitory concentration is 0.
It becomes 39 ppm. However, the actual minimum inhibitory concentration was 0.2 ppm. Therefore, this composition had a synergistic effect when the compounds were used in combination. This was also true for the other compositions.

[0039]

[Table 2] Thus, both compositions had a synergistic effect when the compounds were used in combination.

(Example 2) N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and any one of the compounds (a) to (i) were prepared as shown in Tables 3 and 4 below. The antimicrobial composition was prepared by adding dimethylsulfoxide at the weight ratios shown in Table 1 below. Then, a serially diluted aqueous solution of this antimicrobial composition (0.3 m
1) was added to potato dextrose agar medium (15 ml) to prepare each test medium. Each of the test media was inoculated with the above-mentioned spore suspension (1 ml) for inoculation, and the mixture was incubated at 28 ° C for 7
After culturing for a day, the presence or absence of fungal growth was determined by visual inspection of the fungal growth on the medium. Minimum concentration of a mixture of N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and any of the compounds (a) to (i), which is capable of inhibiting the growth of fungi on the medium. Is the MIC. The MIC for each fungus for each weight ratio of the antimicrobial composition is shown in Tables 3 and 4.

[0041]

[Table 3] Thus, both compositions had a synergistic effect when the compounds were used in combination.

[0042]

[Table 4] Thus, both compositions had a synergistic effect when the compounds were used in combination.

(Example 3) N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and any of the compounds (a) to (i) are shown in Table 5 below. The antimicrobial composition was prepared by adding to dimethyl sulfoxide in each weight ratio. Then, a serially diluted aqueous solution (0.1 ml) of this antimicrobial composition was added to B
Add to old's Basal agar medium (15 ml),
Each test medium was prepared. Each of the test media was inoculated with the above-described inoculation algae suspension (1 ml), and 25 ° C., 1500 lu
After culturing at x for 14 days, the presence or absence of algae growth was determined by visually inspecting the algae growth on the medium. Minimum concentration of a mixture of N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and any of the compounds (a) to (i), which can inhibit the growth of alga on the medium. Is the MIC. The MICs for algae of the antimicrobial composition at each weight ratio are shown in Table 5.

[0044]

[Table 5] Thus, both compositions had a synergistic effect when the compounds were used in combination.

From the results shown in Tables 1 to 5, the antimicrobial composition of the present invention has a higher efficacy and a broader antibacterial spectrum than conventional antimicrobial compositions due to the synergistic effect of the active ingredients. Is shown. Furthermore, it is shown that the concentration of the antimicrobial composition used for inhibiting the growth of the same amount of bacteria, fungi or algae is extremely low as compared with the case where the active ingredient is used alone.

Similar to each of the above-mentioned examples, the composition of the present invention exhibits a good antimicrobial effect even when it is blended with an organic material (for example, fiber, paint, sizing agent, etc.).

[0047]

According to the present invention, N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and the following compounds (a) to (i): (a)
1-[[(3-iodo-2-propynyl) oxy] methoxy] -4-methoxybenzene, (b) 2-n-octyl-4-isothiazolin-3-one, (c) 2-pyridinethiol-1- Zinc oxide salt, (d) 2-bromo-
2-nitro-1,3-propanediol, (e) 5-chloro-2-methyl-4-isothiazolin-3-one,
(F) 2-methyl-4-isothiazolin-3-one,
(G) poly (hexamethylene biguanide) hydrochloride,
(H) 4,4-dimethyloxazolidine, and (i)
An antimicrobial composition containing at least one compound selected from the group consisting of 4- (2-nitrobutyl) morpholine as an active ingredient is obtained. By combining these compounds as active ingredients, a synergistic action of these compounds can be obtained, which is highly safe and highly effective.
Antimicrobial compositions having a broader antimicrobial spectrum are provided. Furthermore, since the concentration of the active ingredient contained in the antimicrobial composition of the present invention can be suppressed to a low level, it can be prepared at extremely low cost, and further has little effect on the environment. The antimicrobial composition of the present invention is effective for the preservation of various industrial waters, industrial products and industrial raw materials, fungi and algae.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A01N 43/80 102 A01N 43/80 102 43/84 101 43/84 101 47/44 47/44 (72) Inventor Takuya Tanaka 236 Nakai, Tatsuno-cho, Tatsuno-shi, Hyogo Prefecture Nagase Chemtex Co., Ltd. (72) Inventor Munehiro Yoshida 1 Kani Honcho, Takamatsu City, Kagawa Prefecture Inui Stock Company (72) Tetsuto Namba Kani Nishi, Takamatsu City, Kagawa Prefecture Honmachi No. 1 Inui Stock Company F-term (reference) 4H011 AA02 BA01 BA06 BB04 BB09 BB10 BB11 BC06 DA13 DD07 DF04

Claims (3)

[Claims] 1. N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide),
An antimicrobial composition containing at least one compound selected from the group consisting of the following compounds (a) to (i): (a) 1-[[(3-iodo-2-propynyl) oxy] Methoxy] -4-methoxybenzene, (b) 2-n
-Octyl-4-isothiazolin-3-one, (c) 2
-Pyridinethiol-1-oxide zinc salt, (d) 2-
Bromo-2-nitro-1,3-propanediol,
(E) 5-chloro-2-methyl-4-isothiazoline-
3-one, (f) 2-methyl-4-isothiazoline-3
-One, (g) poly (hexamethylene biguanide) hydrochloride, (h) 4,4-dimethyloxazolidine, and (i) 4- (2-nitrobutyl) morpholine. 2. The N, N′-hexamethylene bis (4
-Carbamoyl-1-decylpyridinium bromide)
The composition according to claim 1, wherein the weight ratio of the compound to the compound selected from (a) to (i) is in the range of 20: 1 to 1:20. 3. The N, N′-hexamethylene bis (4
-Carbamoyl-1-decylpyridinium bromide)
The composition according to claim 1, wherein the weight ratio of the compound to the compound selected from (a) to (i) is in the range of 5: 1 to 1: 5.