JP2003104802A - Aqueous dispersed antibacterial composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an aqueous dispersed antibacterial composition obtained by blending at least >=1 kind of antibacterial agent with microcapsules containing a dithiol compound or 2,2-dibromo-3-nitrilopropionamide, and a method of disinfection. SOLUTION: This aqueous dispersed antibacterial composition is obtained by blending at least >=1 kind antibacterial agent with the microcapsules containing the dithiol compound or 2,2-dibromo-3-nitrilopropionamide in it for covering the insufficiency of antibacterial activity in the case that a medicinal contact time is short and improving the antibacterial activity much more by a synergistic effect with the combination of the antibacterial technical materials, and the method for disinfection is also provided.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a water-dispersed antibacterial agent composition containing a novel microencapsulated antibacterial agent. More specifically, a dithiol compound or 2,2-dibromo-3-nitrilopropionamide having excellent antibacterial activity is microencapsulated with a polymer film material such as melamine resin or urethane resin in an antibacterial agent of at least another type. The present invention relates to a water-dispersed antibacterial agent composition in which an antibacterial agent is combined.

[0002]

2. Description of the Prior Art Dithiol antibacterial agents or 2,2
-Dibromo-3-nitrilopropionamide (hereinafter DB
Microcapsulated antibacterial agents (referred to as NPA) are known. However, it takes time for the elution amount to reach a certain concentration after addition of the drug, so when immediate effect is required or drug contact time If the length is short, there is a problem that the effect is not sufficiently exerted. Also a dithiol compound,
Many methods have been proposed in which both DBNPA and other drug substances are used to broaden the antibacterial spectrum and exert a synergistic effect. However, depending on the partner compound used in combination, the active ingredient becomes unstable in the formulation when mixed. In many cases, it is difficult to supply it as a mixed preparation because it decomposes. Further, in the case of a compounding agent of a dithiol compound or DBNPA with another antibacterial agent, in a formulation using water as a solvent such as an aqueous solution or an aqueous dispersion,
At present, the active ingredients such as the dithiol compound, DBNPA or the partner compound to be combined are decomposed during the manufacturing process of the preparation or during the storage, so that they are not commercially available. For example, dithiol antibacterial agents and isothiazolone compounds currently on the market, dithiol antibacterial agents and DBN
In mixed preparations of PA, organic solvents such as glycols are used as solvents. Even if an attempt is made to prepare a mixed preparation of 1,2-benzisothiazolin-3-one and dithiol, which are generally supplied in an aqueous solvent, the dithiol compound is decomposed, so that it is difficult to supply the mixed preparation. The use of organic solvent is
According to the Fire Service Law, it is often handled as a dangerous substance, so it is desirable to supply it as an aqueous solution or an aqueous dispersion, but the current situation is that it has not been realized due to the above circumstances. On the other hand, the combination of a dithiol compound and DBNPA, a dithiol compound and methylenebisthiocyanate (hereinafter abbreviated as MBTC), and a combination of a dithiol compound and bis- (1,4-dibromoacetoxy) -2-butene (hereinafter referred to as BBAB) are remarkable synergies. It is well known that the effect is exhibited, but in these mixed preparations, the drug is likely to be decomposed by the reducing agent remaining in the white water, and the efficacy is insufficient in many cases. In consideration of the environment, it is desired to develop a drug that maintains its effectiveness for a long period of time even if the amount used is small.

[0003]

Under these circumstances, the present invention is a harsh use for existing bactericides such as the presence of alkalinity and reducing agents as industrial fungicides and fungicides. Provided is a water-dispersed antibacterial agent composition that has a broader antibacterial spectrum with a smaller amount of drug used in the environment, has immediate effect and long-term sustainability, and further reduces skin irritation. That is the purpose. The target system containing a reducing substance, which is particularly expected to have the effect of the antibacterial composition of the present invention, includes a system containing 1 to 1000 ppm of reducing substance as sulfite ion, and particularly 3 to 3 as sulfite ion. 600ppm
A system containing reducing substances, specifically water-containing pulp made from waste paper pulp or unbleached kraft pulp, white papermaking paper, latex with a reducing agent added during the reaction process, other factory tanks, water in pipes , Drainage, etc.

[0004]

As a result of intensive studies to develop an antibacterial agent having the above-mentioned preferable properties, the present inventors have dissolved a dithiol compound or DBNPA in a hydrophobic solvent to obtain a melamine resin and urethane. By combining at least one other antibacterial agent with an antibacterial agent obtained by microencapsulating a polymer film-forming component such as resin or polyamide resin as a film material, it has a broad antibacterial spectrum that could not be obtained in the past and has immediate effect. The inventor of the present invention has developed a mixed preparation having long-acting and antibacterial activity.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Microencapsulation of a dithiol compound or DBNPA in the present invention can be carried out by previously dissolving a core substance in a hydrophobic solvent and performing a capsule synthesis reaction by an interfacial polymerization method or the like. The obtained microencapsulated antibacterial agent is an aqueous suspension, and the partner compound to be combined can be made into a composition by determining the optimum compounding ratio and compounding amount from the synergistic antibacterial property and the stability of the preparation. . Depending on the partner compound, a surfactant or
A co-solvent may be added in some cases. Hereinafter, the present invention will be described in detail. In the microencapsulated antibacterial agent of the present invention, a dithiol compound or 2,2-dibromo-3-nitrilopropionamide is used as the core substance.
The dithiol compound is a compound represented by the general formula [1].

[0006]

[Chemical 1] (In the formula, R ¹ and R ² are the same or different and each represents a hydrogen atom, a phenyl group or a halogen atom.)

Specific examples of the compound represented by the general formula [1] include 4,5-dichloro-1,2-dithiol-3-
On, 4-phenyl-5-chloro-1,2-dithiol-3-one, 1,2-dithiol-3-one and the like.

As the hydrophobic solvent for dissolving the dithiol compound or DBNPA, the dithiol compound is dissolved and the dithiol is chemically stable to the solvent, and the solvent in which the dithiol is dissolved is brought into contact with water. However, there is no particular limitation as long as the dithiol compound is difficult to elute in the aqueous layer. Examples thereof include hydrocarbon solvents such as hexane, heptane, octane, benzene, toluene, xylene, cyclohexane and the like, hydrocarbon solvents such as aromatic hydrocarbons: kerosene, light oil, paraffin oil and other hydrocarbon solvents: Acetate, propionate, butyrate, lactate, oxalate,
Esters such as crotonic acid ester, salicylic acid ester, benzoic acid ester, phthalic acid ester, adipic acid ester, sebacic acid ester, and phosphoric acid ester: low molecular weight epoxy resins and the like. If the boiling point, nonvolatility, hydrophobicity or the like is required as a solvent condition depending on the capsule formation process or the usage form of the dithiol-containing capsule, the ester or low molecular weight epoxy resin is used as a solvent. What you have to do,
Examples of esters include phthalates such as dimethyl terephthalate, diethyl phthalate, dibutyl phthalate, diheptyl phthalate, dioctyl phthalate, diisodecyl phthalate, butylbenzyl phthalate, dimethyl isophthalate, di-2-ethylhexyl phthalate, ditridecyl phthalate, and dinormal alkyl phthalate. Acid ester: triphenyl phosphate, dibenzyl sebacate, dioctyl sebacate, and the like sebacate ester: triphenyl phosphate, tricresyl phosphate, trioctyl phosphate, octyl diphenyl phosphate, and the like.

Next, examples of the polymer film formed by using a reaction material such as a monomer or a low molecular weight prepolymer include melamine resin and urethane resin. It is a film material that can achieve the intended purpose without losing the drug effect of dithiol. These membrane materials may be appropriately adopted in view of various conditions, economic efficiency, etc. when the microencapsulated preparation is used. The antibacterial agent of the present invention is a dithiol compound or DBPN.
At least one of A, which is microencapsulated with a polymer film-forming component such as melamine resin or urethane resin,
It is a mixture or a dispersion of a seed germicide raw material in a mixing ratio such that a synergistic effect can be enhanced.

The method of using the microencapsulated antibacterial agent composition of the present invention thus obtained is not particularly limited, but it is preferable to disperse it in water or an organic dispersion medium. The organic dispersion medium is not particularly limited, but examples thereof include alcohols such as ethylene glycol, propylene glycol, glycerin, and polyglycerin; glycol ethers such as diethylene glycol monomethyl ether and ethylene glycol monobutyl ether; liquid paraffin; xylene, toluene and the like. Alkylbenzenes; castor oil, soybean oil, olive oil, rapeseed oil and other vegetable oils; cypress oil and other terpenes; polyoxyethylene alkyl ethers and other surfactants. One of these dispersion media may be used,
You may use it in combination of 2 or more type. Further, the microencapsulated antibacterial agent composition of the present invention, carboxymethyl cellulose as a stabilizer, polyvinyl alcohol,
It may contain polyvinylpyrrolidone, sodium alginate, xanthan gum and the like.

As a standard for the concentration of addition of the microencapsulated antibacterial composition of the present invention, for example, synthetic resin emulsion, metal working oil, paint, starch liquid (slurry and paste).
0.5 to 5,000g when used as a preservative
/ ^M is about ^3, and when used as a slime-controlling agent in paper pulp papermaking system, 0.05 to 50 g / ^{m 3}
It is a degree. The microencapsulated antibacterial composition of the present invention is, for example, a cooling water-based or paper pulp paper-making slime control agent, an antiseptic and fungicide such as starch and casein, and a product antiseptic and fungus such as SBR latex, paint and adhesive. As a preservative, antifungal agent using metalworking oils, impregnation / kneading of yarn in textile products,
It can be used very effectively in a wide range of fields as an antiseptic and antifungal agent for wood products.

In the antibacterial composition of the present invention, the immediate effect is not impaired because the combined partner compound exerts antibacterial activity immediately before the drug is sufficiently eluted from the microcapsules immediately after the addition. When two or more kinds of antibacterial agents are simultaneously added to the system, the antibacterial spectrum is expanded, and in the case of ordinary compounding agents, the dithiol compound or DBNPA is decomposed and deactivated depending on the external environment. However, the synergistic effect is sustained because the elution from the capsule is always continued. In addition, by using microcapsules of dithiol compound or DBNPA, it becomes possible to manufacture a new compounding agent with other antibacterial components that could not be conventionally formulated with an aqueous solvent, and the active ingredient in the compounding agent is Also, the problem that the content is reduced due to decomposition during production or storage has been greatly improved.

[0013]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples and Test Examples, but the present invention is not limited to these. Example 1 (2-Brom-2-nitropropane-1,3-
Mixed composition with diol) Microcapsules prepared by dissolving 4,5-dichloro-1,2-dithiole-3-one (hereinafter referred to as dithiol) in dibutyl adipic acid and using a urethane resin as a film material. 2-Brom-2-nitropropane-1,3 to 30 g of antibacterial agent aqueous suspension (containing 6.6% of dithiol)
10 g of diol and 60 g of water were added and mixed to obtain a mixed composition of microcapsules of dithiol and 2-bromo-2-nitropropane-1,3-diol.

Example 2 (mixed composition with 1,2-benzisothiazolin-3-one) A microencapsulated antibacterial agent aqueous suspension prepared by dissolving dithiol in dioctyl adipic acid and using a melamine resin as a film material. 30 g of suspension (containing 6.0% dithiol)
50 g of 1,2-benzisothiazolin-3-one 20% aqueous suspension and 20 g of water are added and mixed, and the microcapsules of dithiol and 1,2-benzisothiazolin-one are mixed.
A 3-on mixed composition was obtained.

Example 3 (mixed composition with 2-methyl-4-isothiazolin-3-one) A microencapsulated antibacterial agent aqueous solution prepared by dissolving DBNPA in dibutyl adipic acid and using a melamine resin as a film material. 40g of suspension (containing 4.5% DBNPA)
2-methyl-4-isothiazolidin-3-one 50
% Aqueous solution 10 g and water 30 g are added and mixed, and DBNPA
A mixed composition of the microcapsules and 2-methyl-4-isothiazolin-3-one was obtained.

Test Example The following reagents were used as test reagents. The agent of the present invention: YMCB-1 (aqueous suspension containing 2 wt% of encapsulated dithiol in terms of dithiol drug substance and 5 wt% of 1,2-benzisothiazolin-3-one) Comparative agent: YB-1 (2 wt of dithiol %, 1,2-benzisothiazolin-3-one Na salt dissolved in 5 wt% triethylene glycol)

Test Example 1 Test conditions Test microorganism: Pseudomonas aerugin
osa (Pseudomonas aeruginosa) PH: 9 Agent of the present invention: YMCB-1 (dithiol and 1,2-
1,1 as the total of benzisothiazolin-3-one
Comparative agent: YB-1 (1,10,3 as the sum of dithiol and 1,2-benzisothiazolin-3-one)
Blank: Drug-free drug evaluation method 10 ml of a carbonate buffer solution having a pH of 9 was dispensed into a test tube for autoclave sterilization. A predetermined amount of the above-mentioned drug was added thereto, and the mixture was shaken for 1 hour at 37 ° C. using a test tube shaking culture machine. Then, a fixed amount of the bacterial solution that had been precultured overnight was added (so that the concentration was 10 ⁸ cells / ml), and the viable cell count was measured over time while shaking. In the meantime, after 2 days and 3 days after the viable cell count was measured, the bacterial solution was re-inoculated to 10 ⁷ cells / ml. The antiseptic effect was examined by measuring the viable cell count in each test solution. The results are shown in Table 1.

[0018]

From Table 1, addition of 1, 10 and 30 ppm of the active ingredient YMCB-1 of the present invention in terms of total drug substance has the same active ingredient content, but has a long-term effect of suppressing viable bacteria even under alkaline conditions as compared with YB-1. It was confirmed to have.

Test Example 2 The following test was carried out for bactericidal efficacy in the presence of a reducing agent. Sodium thiosulfate 50 in pH 7 citrate buffer
ppm was added, and the same test was performed using YMCB-1 used in Test Example 1 and the comparative drug YB-1. The results are shown in Table 2.

[0021] As is clear from Table 2, the drug of the present invention YMCB-1
Compared with YB-1 having the same active ingredient content, showed a viable cell suppression effect even in the presence of a reducing agent.

Test Example 3 Formulation stability test YMCB-1 and YB-1 dithiols and 1,2
The time-dependent change in the content of -benzisothiazolin-3-one (immediately, 2 hours, 6 hours, 1 day, 7 days, 1 month) was measured by liquid chromatography. Measuring method A predetermined amount of YMCB-1 was suspended in an appropriate amount of methyl alcohol. The YMCB-1 suspension was sonicated for a certain period of time to break the capsule, and dithiol and 1,2-benzisothiazolin-3-one were extracted with methyl alcohol. The extract was filtered with a 0.45 μm filter (“PTFE membrane filter” manufactured by ADVANTEC Toyo Co., Ltd.) and the filtrate was adjusted with methyl alcohol, and then the dithiol concentration and the 1,2-benzisothiazolin-3-one concentration were adjusted to HP.
It quantified by LC method. Similarly to YMCB-1, YB-1 was dissolved in methyl alcohol in a predetermined amount, and then the dithiol concentration and the 1,2-benzisothiazolin-3-one concentration were determined by the HPLC method.

[0023] As is clear from the above data, the dithiol in YB-1 is decomposed and hardly remains, while
MCB-1 showed no decrease in dithiol content.

Test Example 4 The following reagents were used as test reagents. Inventive agent YMCB-2: (2 wt% of encapsulated dithiol in terms of dithiol drug substance, 2-bromo-2-
Aqueous suspension containing 5 wt% of nitropropane-1,3-diol) YB-2: (2 wt% of dithiol, 2-bromo-2-
Methylcarbitol solution containing 5 wt% of nitropropane-1,3-diol) Test conditions Test microorganism: Pseudomonas aerugin
osa (Pseudomonas aeruginosa) pH: 9 Agent of the present invention: YMCB-2 (dithiol and 2-bromo-
2-nitropropane-1,3-diol total 1,1
Comparative agent: YB-2 (dithiol and 2-bromo-2-nitropropane-1,3-diol total 1,10,3)
0 ppm) Blank: (without addition of chemicals) Evaluation method 10 ml of a carbonate buffer solution having a pH of 9 was dispensed into a test tube for autoclave sterilization. A predetermined amount of the above-mentioned drug was added thereto, and the mixture was shaken for 1 hour at 37 ° C. using a test tube shaking culture machine. After that, a certain amount of the bacterial solution that had been pre-cultured overnight was added (to 10 ⁸ cells / ml) and the viable cell count was measured over time with shaking (1 hour, 2 hours, 1
Days, 2 days, 3 days, 7 days). Meanwhile, two days later, three
After the number of viable bacteria was measured after the day, the bacterial solution was re-inoculated to 10 ⁷ cells / ml. The antiseptic effect was examined by measuring the viable cell count in each test solution. The results are shown in Table 4.

[0025]

Test Example 5 Formulation stability test Time-dependent changes in the contents of dithiol and 2-bromo-2-nitropropane-1,3-diol in YMCB-2 and YB-2 (immediately after 1 hour, 1 After 7 days, 30 days,
After 60 days and 90 days) was measured by liquid chromatography.

[0027] As shown in Table 5, the content of both active ingredients in YB-2 was retained for about 1 week, but after 30 days, YB-
In No. 2, both dithiol and 2-bromo-2-nitropropane-1,3-diol tended to lower the drug substance content.

Test Example 6 YMCB-1 and YB-1 were added to the coating color (pH 9.1), and the drug residual ratio of dithiol and 1,2-benzisothiazolin-3-one was measured at 35 ° C. The results are shown in Table 6.

[0029]

Test Example 7 SBR latex (pH 8.9) was mixed with YMCB-1 and YB.
-1 was added, and the drug residual ratio of dithiol and 1,2-benzisothiazolin-3-one was measured at 35 ° C. The results are shown in Table 7.

[0031]

Test Example 8 YMCB-2 and YB-2 were added to industrial cooling water (pH 8.3).
Was added, and the drug residual ratio of dithiol and 2-bromo-2-nitropropane-1,3-diol was measured at 35 ° C. The results are shown in Table 8.

[0033]

Test Example 9 Dithiol microcapsule dispersion (dithiol,
The sterilization time was compared using a 20% methyl carbitol solution containing 4.5%) and dithiol. To measure the sterilization time under alkaline conditions, the pH was adjusted to 9, and 30 ppm of the dithiol microcapsule dispersion was added to the bacterial solution in which the viable cell count (Pseudomonas aeruginosa) had been measured in advance. The viable cell count was measured after 10 minutes, 20 minutes, 30 minutes, and 1 hour. Similarly, dithiol microcapsule dispersion 1
5 ppm of dithiol in methyl carbitol solution 15
Similarly, the number of viable bacteria was measured after 10 minutes, 20 minutes, 30 minutes and 1 hour after the addition of ppm. The results are shown in Table 9.

[0035] As is clear from Table 9, when the viable cell count up to 20 minutes after the addition was compared with the dithiol microcapsule single agent and the dithiol microcapsule mixed preparation, a clear difference was observed in the speed of reduction of the cell count.

[0036]

EFFECTS OF THE INVENTION The microencapsulated antibacterial composition of the present invention (1) can improve the antibacterial activity at the initial stage of addition of a dithiol compound or a DBNPA microcapsule formulation, and can improve immediate effect. (2) Conventional dithiol A compound formulation can be manufactured even in combination with an antibacterial agent, which was difficult to formulate a complex formulation with a compound or DBNPA due to decomposition, etc. (3) Due to the sustained release function of dithiol or DBNPA microcapsules, multiple active ingredients Since it exists in the antibacterial system for a long period of time, it can be treated with a small amount due to the expansion of the antibacterial spectrum and the synergistic effect of multiple components. (4) Since a single drug is not used for a long time, resistant bacteria emerge. It is difficult to do so.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A01N 43/80 102 A01N 43/80 102

Claims (2)

[Claims] 1. An antibacterial agent obtained by microencapsulating a solution of a dithiol compound or 2,2-dibromo-3-nitrilopropionamide in a hydrophobic solvent with a polymer film-forming material.
2-bromo-2-nitropropane-1,3-diol,
2,2-dibromo-3-nitrilopropionamide,
4,5-dichloro-1,2-dithiolan-3-one,
1,2-benzisothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-n-octyl-4-isothiazolin-3 -One, 4,5-dichloro-2-n-octyl-3 (2H) isothiazoline, methylenebisthiocyanate, bis- (1,4-dibromoacetoxy) -2-butene, benzyl bromoacetate,
Sodium bromide, α-bromocinnamaldehyde, 2
-Pyridinethiol-1-oxide sodium, bis (2-pyridinethiol-1-oxide) zinc, 2-
(4-thiazolyl) benzimidazole, hexahydro-1,3,5-tris- (2-hydroxyethyl) -S
-Triazine, bis (trichloromethyl) sulfone, dithiocarbamate, 3,5-dimethyltetrahydro-
1,3,5,2H-thiadiazin-2-thione, bromoacetic acid ethylthiophenyl ester, bromoacetic acid ethylthiophenyl ester, α-chlorobenzoaldoxime acetate, 2,2-dibromo-2-nitroethanol,
2,4,5,6-tetrachloroisophthalonitrile, 1
-Bromo-3-chloro-5,5-dimethylhydantoin, 3-bromo-1-chloro-5,5-dimethylhydantoin, 1,2-dibromo-2,4-dicyanobutane,
An aqueous dispersion antibacterial composition comprising a combination of at least one selected from 3-iodo-2-propenylbutyl carbamate, salicylic acid, sodium salicylate, paraoxybenzoic acid ester and p-chloro-m-xylenol. 2. The microcapsulated antibacterial agent comprises dithiol compound microcapsules and 2,2-dibromo-3.
-The water-dispersed antibacterial agent composition according to claim 1, which is a combination of microcapsules of nitrilopropionamide.