JP4498794B2 - Antibacterial and antifungal agent for wet fiber or paper products - Google Patents

Description

  The present invention relates to an antibacterial and antifungal agent that exhibits excellent antibacterial properties against a wide range of microorganisms such as bacteria and fungi, and is less irritating to the skin. The present invention relates to an antibacterial and antifungal agent used in industrial products that have an extremely high chance of direct contact with skin.

Conventionally, various antibacterial and antifungal agents have been used to prevent contamination of industrial products due to the propagation of microorganisms such as bacteria and fungi (eg, moths, mushrooms and yeasts). Examples of the active ingredients of these antibacterial and antifungal agents include various drugs such as quaternary ammonium salt compounds (such as benzalkonium chloride), parabens, and alcohols (such as ethanol).
Among them, N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide), which is a quaternary ammonium salt compound, is characterized by its strong anti-wrinkle effect against wrinkles and low skin irritation. It attracts attention in the field where action is required (see, for example, JP 2000-198879 A).

However, when the above-mentioned various drugs are used alone, a large amount of the drug is required in order to have a sufficient effect as a bactericidal agent, causing a problem of skin irritation as well as cost. In addition, known formulations based on combinations of these respective drugs are all less effective against wrinkles, and wrinkles often occur during the storage period of industrial products.
Similarly, in the case of N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide), a single agent is not sufficiently effective against a wide range of bacteria and sputum for low concentration use. is there. Specifically, there was a problem that the effect was weak against moss such as Aspergillus niger and Penicillium citrinum.

Therefore, as described in JP-A-2003-81713, by combining this N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) with other antibacterial agents, a wide range of microorganisms can be obtained. Attempts have been made to develop antibacterial agents that can be used.
However, although this publication mentions safety with respect to humans and the environment, it does not pursue various problems when directly contacting human skin, such as irritation to the skin.
JP 2000-198879 A JP 2003-81713 A

In consideration of the above points, the present invention has an excellent bactericidal property and durability against a wide range of microorganisms such as bacteria and fungi even at low concentrations, and the production cost as a result of low concentration use. providing antibacterial and antifungal agents which can also reduce the skin irritation low and one wet state, i.e. at low concentrations even under the conditions where bacteria or fungi, is in easy circumstances breed It is an object of the present invention to provide an antifungal and fungicidal agent that can maintain excellent bactericidal properties over a long period of time.

In order to solve the above problems, the present inventor can maintain an excellent antibacterial and antifungal effect over a long period of time, despite the use of a low concentration, particularly in a wet state where bacteria and fungi are easy to propagate. In addition, earnest research was repeated on combinations of various drugs with little skin irritation.
As a result, N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide), N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium acetate), and 2-benzimidazolecarbamine According at least one of methyl-dodecylbenzene sulfonate, a N- substituted benzisothiazolin-based compound represented by the following general formula I, the most expedient be Awa assembled, moreover in this combination As a result, it was found that the irritation to human skin can be reduced, and the present invention has been completed.

That is, the present invention is an antibacterial and antifungal agent used in wet fiber or paper products that are in direct contact with human skin ,
Effective component, (A) N, N'-hexamethylene-bis (4-carbamoyl-1-decyl pyridinium bromide), N, N'-hexamethylene-bis (4-carbamoyl-1-decyl pyridinium acetate), 2- A combination of at least one of methyl benzimidazolecarbamate / dodecylbenzenesulfonate and (B) N-butylbenzisothiazolin-3-one represented by general formula I, wherein (A) and ( B) at a weight ratio (a) :( B) = 1 : 99~99: a feature in that it contains a ratio of 1.
In the following formulas, R represents shows the butyl group.

The antibacterial and antifungal agents of the present invention include N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium acetate). And at least one of methyl 2-benzimidazolecarbamate · dodecylbenzenesulfonate and N-butylbenzisothiazolin-3-one represented by the above general formula I as active ingredients.

  The above N, N′-hexamethylene bis (4-carbamoyl-1-decylpyridinium bromide) and N, N′-hexamethylene bis (4-carbamoyl-1-decylpyridinium acetate) are cationic polymer antiseptic / antifungal agents. What is necessary is just to use what is generally marketed as this.

  Methyl 2-benzimidazolecarbamate / dodecylbenzenesulfonate is an antifungal agent that exhibits excellent effects on moss such as Aspergillus niger and Penicillium citrinum, and is generally marketed. Can be used as is.

The N-substituted benzisothiazoline-based compound is represented by the above general formula I.
R in Formula I represents a hydrocarbon group which may have a substituent, specifically, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, or an alkylthio group. Carbon atoms such as alkyl groups, cycloalkyl groups, alkenyl groups, aralkyl groups, aryl groups, etc., which may have a substituent such as carboxyl group or ester thereof, halogen atom, carbonyl group, cyano group, etc. Indicates a hydrogen group.
In addition, the benzene ring of the compound represented by the general formula I may have a substituent, specifically, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a nitro group. , Alkylthio groups, carboxyl groups or esters thereof, and substituents such as halogen atoms.

Specific examples of the N-substituted benzisothiazoline compound represented by the general formula I include N-methylbenzisothiazoline-3-one, N-ethylbenzisothiazoline-3-one, N-propylbenzisothiazoline-3-one, N-butylbenzisothiazoline-3-one, N-isobutylbenzisothiazoline-3-one, N-phenylbenzisothiazoline-3-one, benzisothiazoline-3-thione, N-methylbenzisothiazoline-3-thione, N-ethyl Examples include benzisothiazoline-3-thione and benzisothiazoline-3-one. Among them, N-butylbenzisothiazolin-3-one is an object of the present invention (low concentration, and bacteria and fungi are easy to reproduce. High antibacterial and antifungal effect over a long period under wet conditions, and low Preferred in achieving obtaining a skin irritation).
Further, this N-butylbenzisothiazolin-3-one can maintain an antibacterial or antifungal effect for a long period of time, has low inhalation toxicity of volatile matter (that is, the volatile matter itself is small, and should be volatile) Since the toxicity is low even if inhaled, and it is easy to handle, it has been widely used mainly when targeting fungi.
In addition, what is generally marketed can be used for N-butylbenzisothiazolin-3-one as it is.

In the present invention, among these four components, N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) and N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium) Acetate) and methyl 2-benzimidazolecarbamate / dodecylbenzenesulfonate as “component (A)” and N-butylbenzisothiazolin-3-one represented by the above general formula I as “(B) as component ", it contains such a combination of components (a) and (B) components.
By using such a combination, the antibacterial / antifungal effect and the suppression of skin irritation more than when the above four components are used alone or when the three compounds of component (A) are mixed and used. In particular, in the wet state, the above effect can be maintained over a long period even when used at a low concentration, and the irritation to human skin can be reduced. it can.

The blending ratio of the component (A) and the component (B) is within the range of 1:99 to 99: 1, preferably 10:90 to 90:10 by weight, and the types of industrial products to be used and their use It is selected appropriately according to the conditions to be performed.
By selecting an appropriate blending ratio, the activity of each active ingredient is enhanced even in a wet state or at a low concentration, and the antibacterial / antifungal agent, which is a composition thereof, varies over a long period of time. The reason for this is that it is estimated that the parts that stimulate the human skin cancel each other within the range of this compounding ratio, although the reason is unknown in detail. Thus, skin irritation can be suppressed as much as possible.

As described above, the antibacterial and antifungal agent of the present invention contains ( A) component and (B) component as active ingredients.
In the case of the component containing the component (A) and the component (B), a combination of two compounds of any one compound of the component (A) and the compound of the component (B), and any of the components (A) There are a combination of two compounds and a compound of component (B), and a combination of all three compounds of component (A) and a combination of four compounds of component (B). .
By using a composition comprising these two, three or four compounds, the present invention can be used at a low concentration and in a wet state in which bacteria and fungi can easily propagate for a long period of time. Antibacterial and antifungal effects can be maintained.

Also, in terms of skin irritation, the reason is unknown in detail, but when each compound is used alone due to the action that the skin irritation part of each compound is presumed to be the covering action of other compounds. In comparison, the skin irritation reducing effect can be obtained while maintaining an excellent antibacterial and antifungal effect.
This covering action is particularly well expressed when combining the component (A) and the component (B), and it is possible to obtain a skin irritation reducing effect while maintaining an excellent antibacterial and antifungal effect. .

(A) When it is set as the composition which consists of 3 types of compounds of 2 compounds in a component, and (B) component, or from 4 types of compounds of 3 compounds in (A) component, and (B) component In the case of the composition to be formed, the compounding ratio of each compound in the component (A) is not strictly limited and can be changed according to the use of the obtained antibacterial / antifungal agent. Two or three compounds in an appropriate combination can be selected from the three compounds, and can be blended in an optimum blending amount within the range of 1 to 99 parts by weight, preferably 10 to 90 parts by weight.
With this blending amount, the above-mentioned antibacterial / antifungal effect and skin irritation suppressing effect can be obtained effectively.

  The antibacterial and antifungal agent of the present invention is a known additive, for example, other bactericides, surfactants, antioxidants, in the range of not inhibiting the excellent effects of the present invention in its intended purpose and application. You may add an antifoamer, a thickener, a natural product extract, etc.

  Other fungicides that can be used in common with the antifungal agent of the present invention include, for example, the above-mentioned 2-benzimidazole carbamate methyl dodecylbenzene sulfonate, methyl paraben, ethyl paraben, paraoxybenzoates, Examples include quaternary ammonium salts such as chlorhexidine gluconate and benzalkonium chloride, phenoxyethanol, sodium benzoate, and ethyl alcohol.

Examples of the surfactant include nonionic, cationic, and anionic surfactants. Specific examples include polyoxyalkylene alkyl ether, polyoxyalkylene alkylphenyl ether, and polyoxyalkylene. Higher alcohol ether, oxyethylene / oxypropylene block polymer, sorbitan fatty acid ester, polyoxyalkylene sorbitan alkyl ester, alkylbenzene sulfonic acid, alkyl sulfate ester salt, polyoxyethylene alkylamine, etc. alone or in combination Can be used.

The antibacterial and antifungal agent of the present invention comprising the above components may be appropriately prepared in a known form such as a powder, a granule or a liquid depending on the purpose of use.
In general, it is preferable to prepare as a liquid from the viewpoint of handleability, but in some cases, it can also be formulated as an emulsion or suspension.
In order to prepare as a liquid agent, the active ingredient may be dissolved in a solvent and appropriately mixed by stirring.

Such a solvent is not particularly limited as long as it can dissolve or disperse the above active ingredients, and examples thereof include water, alcohols, ethylene glycol, diethylene glycol, propylene glycol, polyethylene glycol, and ethylene glycol monomethyl ether. , Glycols such as ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, esters such as ethyl acetate and dimethyl maleate, ketones such as acetone and methyl ethyl ketone, aromatics such as toluene and xylene , Dimethylacetamide, dimethylformamide, dimethyl sulfoxide, dioxane, propylene carbonate, tetrahydrofuran, - methylpyrrolidone, .gamma.-butyrolactone, diethylene glycol diacetate, diethylene glycol monoethyl ether acetate, and the like triacetate glycerol. These solvents may be used alone or in combination of two or more.
There is no restriction | limiting in particular in the usage-amount of a solvent, What is necessary is just to select suitably according to the chemical | medical agent to be used, the dosage form to employ | adopt, the preparation method to employ | adopt.

The antibacterial / antifungal agent of the present invention exhibits an excellent microbial control effect when added to an object.
This object is obtained from the characteristics of the antibacterial / antifungal agent of the present invention (such as being able to maintain antibacterial / antifungal over a long period of time at a low concentration in a wet state, and low skin irritation). Paper products, especially industrial products that have many opportunities to come into direct contact with human skin, such as those products that are marketed in the wet state, are preferred, but in addition to these, they are applicable to most of those that require microbial control. Is possible.

  There are no particular restrictions on the types of fiber products and paper products. As described above, the antibacterial and antifungal agent of the present invention has low skin irritation and prevents the growth of a wide range of microorganisms over a long period of time. In particular, wet tissues, wet towels (care cloths), toiletries, cleaning products (specifically, wet flooring wipers, wet wipers marketed as car products, etc.), towels ( It can be used in a wide range such as a hand towel for meals).

  In the present invention, the moisture content in the product in the wet state is not particularly limited, and a normal moisture content in these products is sufficient. For example, the product body (in a state before the wet state) It may be within a range of about 50 to 500% by weight with respect to the weight of.

In order to apply the antibacterial / antifungal agent of the present invention to the above-mentioned textile products and paper products, the antifungal / antifungal agent of the present invention is in the form of an organic solvent solution, aqueous emulsion, suspension, etc. In addition, it may be applied by an appropriate method such as spraying, coating, or dipping, or may be in the form of a powder or tablet, dissolved in an appropriate solvent before use, and applied by an appropriate method such as spraying, coating, or dipping. Good.
In addition, in a wet product, the antibacterial / antifungal agent of the present invention can be added to a liquid for making a wet state.

The concentration at the time of adding the antibacterial / antifungal agent of the present invention to the sterilization target as described above (such as fiber products and paper products as described above) is the target to be used (wet tissue, wet wiper, meal wipes, etc.) In general, however, the above-described object of the present invention is effectively exhibited when the concentration is 1 to 1000 ppm, preferably about 50 to 500 ppm, as the active ingredient.
That is, if it is less than 1 ppm, a practical antibacterial / antifungal effect cannot be obtained, and there is no sustainability of the effect over a long period of time. The skin irritation may become too strong.

According to the antibacterial and antifungal agent of the present invention, an effective antibacterial and antifungal effect can be exhibited at low concentrations over a long period of time, not only for bacteria but also for fungi such as sputum.
Moreover, according to the antibacterial and antifungal agent of the present invention, it can be prepared not only at a very low price, but also has low skin irritation and can be applied to various textile products and paper products.

[Formulation example]
The formulation of the formulation example is shown below. In addition, the part in a formulation example means a weight part.

Formulation Example 1
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 15 parts N-butylbenzisothiazolin-3-one 5 parts

Formulation Example 2
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 2 parts N-butylbenzisothiazolin-3-one 20 parts

Formulation Example 3
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 15 parts N-ethylbenzisothiazolin-3-one 5 parts

Formulation Example 4
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 1.5 parts N-ethylbenzisothiazolin-3-one 20 parts

Formulation Example 5
2-Benzimidazole carbamate methyl dodecylbenzenesulfonate 12 parts N-butylbenzisothiazolin-3-one 1 part

Formulation Example 6
2-Benzimidazole carbamate methyl dodecylbenzenesulfonate 1 part N-butylbenzisothiazolin-3-one 20 parts

Formulation Example 7
2-Benzimidazole carbamate methyl dodecylbenzenesulfonate 15 parts N-phenylbenzisothiazolin-3-one 2 parts

Formulation Example 8
2-Benzimidazolecarbamate methyl dodecylbenzenesulfonate 1 part N-phenylbenzisothiazolin-3-one 18 parts

Formulation Example 9
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 5 parts 2-benzimidazole carbamate methyl dodecylbenzenesulfonate 3 parts N-butylbenzisothiazolin-3-one 12 parts

Formulation Example 10
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 4 parts 2-Benzimidazole carbamate methyl dodecylbenzenesulfonate 6 parts N-butylbenzisothiazolin-3-one 3 parts

Formulation Example 11
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 5 parts 2-benzimidazole carbamate methyl dodecylbenzenesulfonate 5 parts N-methylbenzisothiazolin-3-one 10 parts

Formulation Example 12
N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 5 parts 2-Benzimidazole carbamate methyl dodecylbenzenesulfonate 6 parts N-phenylbenzisothiazolin-3-one 2 parts

Formulation Example 13
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide) 10 parts 2-Benzimidazole carbamate methyl dodecylbenzenesulfonate 6 parts

Formulation Example 14
N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium acetate) 15 parts N-butylbenzisothiazolin-3-one 5 parts

Comparative Formulation Example 1
20 parts of N, N'-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide)

(Measurement of minimum growth inhibitory concentration of microorganisms)
For Formulation Examples 1 to 14 and Comparative Formulation Example 1, plate media containing a predetermined concentration of the drug were prepared, and Aspergillus niger, Penicillium citrinum and Gliocladium bilens (Gliocladium) virens), the test bacterial solution was smeared, and cultured in a thermostat at 28 ± 2 ° C. for 2 weeks.
The concentration at which no growth was observed after culturing was validated, and the microbial minimum growth inhibitory concentration was measured. The results are shown in Table 1.

  As is apparent from Table 1, the minimum microbial growth inhibitory concentrations of Formulation Examples 1 to 14 are ascertained for any of Aspergillus niger, Penicillium citrinum, and Gliocladium virens. Is 300 mg / l or less. According to the present invention, it can be seen that an effect is obtained against a wide range of microorganisms.

[Application example]
Formulation Examples 1 to 14 and Comparative Formulation Example 1 were impregnated with a non-woven fabric for wet tissue so as to have a chemical (in the formulation example) concentration of 1000 ppm to obtain test pieces.
On the other hand, a mixed spore suspension of Aspergillus niger, Penicillium citrinum, and Gliocladium virens was prepared as a test bacterium.
The above-mentioned test piece was placed on the center of a prepared plate agar medium, and 1 ml of the above mixed spore suspension was sprinkled on it.
This is cultured for 2 weeks in an incubator at 28 ± 2 ° C., the state of mold growth is observed, and “0” is indicated when no hyphae growth is observed in the inoculated part of the test piece. Table 2 shows the case where the area of the hyphae growth part does not exceed 1/3 of the total area as "1" and the case where the area of the hyphae growth part of the test piece exceeds 1/3 of the total area as "2".

As is apparent from Table 2, for Formulation Examples 1, 2, 5, 6, 9, 10, and 14, mold growth was not observed on the test piece even on the 14th day.
For Formulation Examples 3, 4, 7, 8, 11, 12, and 13, mold growth was suppressed until day 7, but mold growth was observed on the test piece on day 14, and mold was observed. It was confirmed that the growth of the plant was somewhat active.
On the other hand, in Comparative Formulation Example 1, mold growth was observed on the fourth day.

In addition, when wet tissue added with the above formulation examples was used for 2 weeks every day for 5 minutes, human skin was contacted with each other for formulation examples 1, 2, 5, 6, 9, 10, and 14. There were no abnormalities.
For Formulation Examples 3, 4, 7, 8, 11, 12, and 13, some erythema occurred in the second week, but no abnormality was observed after the test was completed and contact was lost.

The antibacterial / antifungal agent of the present invention is only added to an object, prevents microorganisms from spreading over a wide range in a wet state for a long period of time, and exhibits an excellent antifungal / antifungal effect.
And since the density | concentration of each active ingredient contained can be restrained low, it can be prepared very cheaply.
Moreover, since the antifungal and fungicidal agent of the present invention has low skin irritation, there are many opportunities to directly touch human skin, or various textile products and paper products for human skin, which are wet. It can be effectively applied to commercial products.

Claims (1)

An antibacterial and antifungal agent used in wet fiber or paper products that come into direct contact with human skin,
The active ingredient is
( A) N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium bromide), N, N′-hexamethylenebis (4-carbamoyl-1-decylpyridinium acetate), methyl 2-benzimidazole carbamate Any one or more selected from dodecylbenzenesulfonate ,
( B) a combination of N-butylbenzisothiazolin-3-one ,
Bactericidal and antimicrobial use for wet fibers or paper products, wherein the content ratio of ( A) and (B) is (A) :( B) = 1: 99 to 99: 1 in weight ratio Glaze.