JP2009149574A - Antimicrobial agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an antimicrobial agent having high antimicrobial activity and less irritation in skin, etc. <P>SOLUTION: The antimicrobial agent consisting of a quaternary ammonium salt is expressed by general formula (1), wherein R<SP>1</SP>is a 6-24C hydrocarbon group; R<SP>2</SP>is a 1-24C hydrocarbon group; R<SP>3</SP>is a 1-5C hydrocarbon group which may be substituted by hydroxy; R<SP>4</SP>and R<SP>5</SP>are each a 2-6C alkylene; (n) is a number of 0.3 to 20; (m) is a number of 0.3 to 10; (p) is an integer of 1 to 3; (q) is 1 or 2; (r) and (s) are each an integer of 0 to 2; (p+q+r+s)=4; and A<SP>-</SP>is an anion. An antimicrobial composition containing the agent is also provided. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an antibacterial agent. Specifically, the present invention relates to an antibacterial agent having high antibacterial activity against Staphylococcus aureus and Escherichia coli and having low skin irritation and an antibacterial composition containing the same.

  Cationic surfactants have antibacterial and bactericidal action and are used as antibacterial agents, bactericides, disinfectants and the like. For example, disinfectants for medical equipment and affected areas, medical cleaners such as cleaning, household cleaners such as household dishes, food industry cleaners, antibacterial processing of textiles and synthetic resins, wood, daily necessities, shampoos, etc. Widely used in rinsing, cosmetics, etc.

As such, the cationic surfactants conventionally used as antibacterial agents and the like include alkyltrimethylammonium salt, alkyldimethylethylammonium salt, alkyldimethylbenzylammonium salt, dialkyldimethylammonium salt, alkylpyridinium salt, And quaternary ammonium salts such as alkylquinolinium salts (for example, see Non-Patent Documents 1 and 2). However, these conventional quaternary ammonium salts have drawbacks such as great irritation to the skin.
"Anti-bacteria-proof handbook", Gihodo Publishing Co., Ltd., published on May 25, 1986, P510-511 "New edition surfactant handbook", Engineering Books Co., Ltd., October 1, 1987, P538

  An object of the present invention is to provide an antibacterial agent, more specifically, an antibacterial agent having high antibacterial activity and less irritation on the skin or the like.

  The present invention is an antibacterial agent comprising a quaternary ammonium salt represented by the general formula (1) (hereinafter referred to as quaternary ammonium salt (1)), and an antibacterial composition containing the antibacterial agent.

(In the formula, R ¹ is a hydrocarbon group having 6 to 24 carbon atoms, R ² is a hydrocarbon group having 1 to 24 carbon atoms, and R ³ is a hydrocarbon optionally substituted with a hydroxy group having 1 to 5 carbon atoms. Group, R ⁴ and R ⁵ each independently represents an alkylene group having 2 to 6 carbon atoms, n represents a number of 0.3 to 20 indicating the average number of added moles of the oxyalkylene group, and m represents an average of the oxyalkylene group. the number of 0.3 to 10 indicating the number of added moles, p is an integer of 1 to 3, q is 1 or 2, r and s are each independently an integer of 0 to 2, is p + q + r + s = 4 .A - Represents an anion.)
In addition, the quaternary ammonium salt (1) which is the antibacterial agent of the present invention is used for the purpose of antibacterial, sterilization, disinfection, antifungal and the like, and they are collectively referred to as an antibacterial agent.

  According to the present invention, an antibacterial agent having high antibacterial activity and less irritation on the skin or the like can be provided.

  In the quaternary ammonium salt (1), p is an integer of 1 to 3, and 1 or 2 is preferable and 1 is more preferable from the viewpoint of ease of production and cost.

R ¹ is a hydrocarbon group having 6 to 24 carbon atoms, preferably a hydrocarbon group having 8 to 22 carbon atoms, and more preferably an aliphatic hydrocarbon group. Further, when p is 1, R ¹ is preferably an aliphatic hydrocarbon group having 10 to 22 carbon atoms, more preferably a linear or branched alkyl group having 12 to 18 carbon atoms, and 12 to 18 carbon atoms. A linear alkyl group is more preferred. When p is 2, R ¹ is preferably an aliphatic hydrocarbon group having 8 to 16 carbon atoms, more preferably a linear or branched alkyl group having 8 to 14 carbon atoms, and a linear chain having 8 to 12 carbon atoms. Are more preferable, and a linear alkyl group having 10 carbon atoms is particularly preferable.

R ² is a hydrocarbon group having 1 to 24 carbon atoms, preferably an aliphatic hydrocarbon group having 1 to 24 carbon atoms, more preferably a linear or branched alkyl group having 1 to 3 carbon atoms, A linear alkyl group of 1 or 2 is more preferred, and a methyl group is particularly preferred.

R ³ is a hydrocarbon group which may be substituted with a hydroxy group having 1 to 5 carbon atoms, preferably an aliphatic hydrocarbon group which may be substituted with a hydroxy group having 1 to 3 carbon atoms, A linear alkyl group having 1 or 2 or a hydroxyalkyl group having 2 or 3 carbon atoms is more preferable, and a methyl group, an ethyl group, or a hydroxyethyl group is still more preferable.

R ⁴ and R ⁵ are each independently an alkylene group having 2 to 6 carbon atoms, which may be linear or branched, but is preferably a linear or branched alkylene group having 2 to 4 carbon atoms, More preferred are 3 linear or branched alkylene groups.

  n is a number of 0.3 to 20 indicating the average number of added moles of the oxyalkylene group, preferably a number of 0.5 to 10, and more preferably 0.7 to 3. m is a number of 0.3 to 10 indicating the average number of added moles of the oxyalkylene group, preferably a number of 0.5 to 5, and more preferably 0.7 to 3.

  q is 1 or 2, and when p is 1, q is preferably 1 or 2, and when p is 2 or 3, q is preferably 1. r is an integer of 0 to 2, and when p is 1, r is preferably 0 or 1, and when p is 2 or 3, r is preferably 0. s is an integer of 0-2, and 1 is preferable. However, p + q + r + s = 4.

A ⁻ is an anion, specifically, halogen ions such as Cl ⁻ and Br ⁻ , alkyl sulfate ions such as methyl sulfate and ethyl sulfate, sulfate ions, paratoluene sulfonate ions, alkyl such as methyl phosphate and ethyl phosphate. Phosphate ion, phosphate ion, carbonate or carbonate ion, formic acid, acetic acid, propionic acid, butyric acid, glycolic acid, gluconic acid, lactic acid, glutamic acid, malic acid, tartaric acid, citric acid, maleic acid, malonic acid, succinic acid Organic acid ions such as From the viewpoint of ease of production and cost, Cl ⁻ , Br ⁻ , methyl sulfate ion, ethyl sulfate ion, p-toluenesulfonate ion, carbonate and carbonate ion, and acetic acid, propionic acid, glycolic acid, gluconic acid, lactic acid An organic acid ion selected from the group consisting of Cl ⁻ , methyl sulfate ion, ethyl sulfate ion, and an organic acid ion selected from acetic acid, propionic acid, and glycolic acid is more preferable.

  Although the manufacturing method of quaternary ammonium salt (1) is not specifically limited, For example, it can manufacture by the following method.

Alkylene oxide is reacted with the alcohol corresponding to R ¹ using a catalyst such as an alkali or acid as necessary, and distillation is performed as necessary to obtain an alkyl ether alcohol compound. Alternatively, an alkyl halide or alkyl sulfate corresponding to R ¹ is reacted with an alcohol corresponding to R ⁴ or an alcoholate compound thereof, and if necessary, purification such as removal of by-product salt or distillation is performed to obtain an alkyl ether alcohol. Compounds can also be obtained.

  This alkyl ether alcohol compound is reacted with an amine in the presence of an amination catalyst, and distillation is performed as necessary to obtain an alkyl ether type amine. In addition, the alkyl ether alcohol compound is reacted with a halogenating agent such as hydrochloric acid or thionyl chloride in the presence of a Lewis acid catalyst such as aluminum chloride, if necessary, and further reacted with an amine to form a salt. An alkyl ether type amine can also be obtained by purification such as removal and distillation. When these alkyl ether type amines are primary amines or secondary amines, reaction with alkyl halides such as methyl chloride, ethyl chloride, methyl bromide or alkylene oxides, and purification such as distillation as necessary To obtain an alkyl ether type tertiary amine.

In addition, after reacting the alcohol corresponding to R ¹ with acrylonitrile in the presence of an alkali metal hydroxide such as lithium hydroxide, sodium hydroxide or potassium hydroxide to obtain alkoxypropionitrile, a cobalt catalyst, nickel Alkoxypropylamine is obtained by hydrogenation using a hydrogenation catalyst such as a system catalyst, a copper catalyst, or a noble metal catalyst. Alkoxypropylamine is disclosed in J. Org. Am. Chem. Soc. 57, page 1505 (1945), British Patent No. 869405, JP-A-48-103505, etc., and if necessary, purification such as distillation may be performed. good. Subsequently, the alkoxypropylamine is subjected to a reductive alkylation reaction described in JP-A No. 2002-256283 or the like, or an alkyl halide such as methyl chloride, ethyl chloride, or methyl bromide or an alkylene oxide is reacted. If necessary, purification such as distillation can be performed to obtain an alkyl ether type tertiary amine.

  Further, the quaternary ammonium salt (1) can be obtained by reacting the alkyl ether type tertiary amine with a quaternizing agent in a solvent such as water or a lower alcohol such as ethanol or isopropyl alcohol.

  Examples of the quaternizing agent include alkyl halides such as methyl chloride, ethyl chloride, and methyl bromide, dialkyl sulfates such as dimethyl sulfate and diethyl sulfate, and alkylene oxides such as ethylene oxide and propylene oxide. In addition, when performing quaternization with alkylene oxide, it is necessary to add an acid which becomes a counter ion, and the timing of adding the acid is added all at once before or during the reaction or after the reaction. .

  The method of using the antibacterial agent of the present invention is not particularly limited, and can be applied to various objects. For example, commonly employed methods such as a method of spraying on an object to be subjected to antibacterial treatment, a method of applying, a method of impregnating the object, and a method of immersing the object can be used as they are. When the antibacterial treatment is actually performed, the antibacterial agent of the present invention may be used as it is, but is usually water or a water-water-soluble organic solvent, preferably 0.001 to 5% by mass, more preferably 0. Used by diluting to about 01 to 1% by mass. Or it can add to these as an antibacterial component contained in a cleaning agent or a disinfectant.

  The antibacterial composition of the present invention contains the antibacterial agent of the present invention, and other components such as a water-soluble organic solvent, a chelating agent, a surfactant, other bactericides, a thickener, a reducing agent, depending on the use. A viscosity agent, a pH adjuster, inorganic salts, a fragrance, a coloring agent, a pearling agent, a bulking agent, an enzyme, an abrasive, a binder and the like can be contained.

  0.001-5 mass% is preferable, as for content of the antimicrobial agent of this invention in the antimicrobial composition of this invention, 0.01-1 mass% is more preferable, and 0.1-1 mass% is still more preferable.

  The antibacterial agent and antibacterial composition of the present invention are used in the same manner as known antibacterial agents, disinfectants, disinfectants, antifungal agents or compositions containing these for the purpose of antibacterial, sterilization, disinfection, antifungal and the like. Can do. The use mode includes: medical cleaning agents for the purpose of disinfecting and cleaning medical instruments and affected parts, household cleaning agents for sterilizing and cleaning dishes, food industry cleaning agents, lubricants for container transfer conveyors, food packaging films , Antibacterial agents for antibacterial processing of fibers, synthetic resins, wood, daily necessities, shampoos, rinses, hand soaps, body soaps, cleansing creams, cosmetics, softeners for clothing, aqueous or non-aqueous paints, Examples include a method of impregnating a nonwoven fabric or the like and using it as a wet tissue, toilet seat cleaner or the like. When used as an antibacterial agent for fibers, all fibers such as cotton, polyester, acrylic and nylon may be treated by a general method such as stirring treatment, dipping treatment, spray treatment and the like. Moreover, it can also apply | coat or spray or inject | pour on the surface to wood, daily necessities, etc. Moreover, when using about synthetic resin etc., you may make it adhere to the surface by apply | coating or spraying after shaping | molding, and can also knead | mix at the time of a shaping | molding process etc. in order to maintain an antimicrobial effect.

Examples 1-8 and Comparative Examples 1-3
As the antibacterial agent, the following antibacterial agent and skin irritation were evaluated using the antibacterial agent of the present invention and the comparative antibacterial agent shown below. The results are shown in Table 1.

<Antimicrobial agent of the present invention>
Quaternary ammonium salt (1-1): In general formula (1), R ¹ is nC ₁₂ H ₂₅ , R ⁴ is —CH ₂ CH ₂ CH ₂ —, n = 1, R ⁵ is —CH _2. Compound in which CH ₂ —, m = 1, R ² = R ³ = methyl group, p = q = r = s = 1, and A ⁻ is Cl ⁻ Quaternary ammonium salt (1-2): General formula (1) ), R ¹ is nC ₁₄ H ₂₉ , R ⁴ is —CH ₂ CH ₂ CH ₂ —, n = 1, R ⁵ is —CH ₂ CH ₂ —, m = 1, R ² = R ³ = methyl. A compound wherein p = q = r = s = 1 and A ⁻ is Cl ⁻ quaternary ammonium salt (1-3): In the general formula (1), R ¹ is n-C ₁₆ H ₃₃ , R ⁴ Is —CH ₂ CH ₂ CH ₂ —, n = 1, R ⁵ is —CH ₂ CH ₂ —, m = 1, R ² = R ³ = methyl group, p = q = r = s = 1, A ⁻ is Cl ^-, compound quaternary ammonium salt (1-4): general formula ( In), R ¹ is _{n-C 14 H 29, R} 4 is _{-CH 2 CH 2 CH 2 -,} n = 1, R 5 is _{-CH 2 CH 2 -, m =} 1, R 2 = R 3 = methyl A compound wherein p = q = r = s = 1 and A ⁻ is CH ₃ CH ₂ COO ⁻ Quaternary ammonium salt (1-5): In the general formula (1), R ¹ is n—C ₁₄ H ₂₉ , R ⁴ is —CH ₂ CH ₂ CH ₂ —, n = 1, R ⁵ is —CH ₂ CH ₂ —, m = 1, R ² is a methyl group, R ³ = is a hydroxyethyl group, p = q = Compound in which r = s = 1 and A ⁻ is CH ₃ COO ⁻ Quaternary ammonium salt (1-6): In the general formula (1), R ¹ is nC ₁₄ H ₂₉ , R ⁴ is —CH ₂ CH ₂ CH ₂ —, n = 1, R ⁵ is —CH ₂ CH ₂ —, m = 1, R ³ = methyl group, p = 1, q = 2, r = 0, s = 1, A ⁻ is Cl ^- compounds wherein the quaternary ammonium salt (1-7): In the general formula (1), R ¹ is n-C ₁₀ H ₂₁ , R ⁴ is —CH ₂ CH ₂ CH ₂ —, n = 1, R ⁵ is —CH ₂ CH ₂ —, m = 1, R ³ = Compound in which methyl group, p = 2, q = 1, r = 0, s = 1, and A ⁻ is Cl ⁻ Quaternary ammonium salt (1-8): In the general formula (1), R ¹ is n− C ₁₄ H ₂₉ , R ⁴ is —CH ₂ CH ₂ —, n = average 1.0, R ⁵ is —CH ₂ CH ₂ —, m = 1, R ² = R ³ = methyl group, p = q = r = S = 1, Compound in which A ⁻ is CH ₃ COO ⁻ <Comparative Antibacterial Agent>
Quaternary ammonium salt (2-1): In the following formula (2), R ⁶ is n-C ₁₄ H ₂₉ , R ² = R ³ = R ⁷ = methyl group, p = q = r = s = 1, a ^- is Cl ^-, compound quaternary ammonium salt (2-2): in formula (2), R ⁶ is _{n-C 10 H 21, R} 3 = R 7 = methyl, p = 2, q = 1, r = 0, s = 1, A ⁻ is Cl ⁻ quaternary ammonium salt (2-3): In the following formula (2), R ⁶ is nC ₁₄ H ₂₉ , R ² = R ⁷ = methyl group, R ³ = benzyl group, p = q = r = s = 1, and A ⁻ is Cl ⁻

<Antimicrobial evaluation method>
As test compounds, the antibacterial agents of the present invention shown in Table 1 and comparative antibacterial agents are used, and MIC (minimum growth inhibitory concentration) and MBC (minimum bactericidal concentration), which are general antibacterial evaluation methods, are diluted in a small amount The antibacterial activity against Escherichia coli (Escherichia coli IFO3972) and Staphylococcus aureus IFO13276 was tested according to the method (Reference: Newly Revised GMP Microorganism Test Method June 1, 2000, Kodansha).

A medium, sterilized water, a specimen (test compound), and each bacterium were placed in a sterilized plastic cell to make a total volume of 200 μL. As the medium, an SCD (SOYBEAN-CASEIN DIGEST BROTH) medium was used as a medium for MIC. The bacterial concentration was about 2 × 10 ⁶ CFU / mL (CFU: Colony Forming Unit). Test compound concentrations were adjusted to 400, 200, 100, 50, 25, 12.5, 6.3, 3.1, 1.6, 0.8, 0.4, and 0.2 ppm. Then, after culturing at 35 ° C. for 24 hours, the MIC of bacterial growth was determined with a turbidimeter. Subsequently, the internal solution of the cell in which no bacterial growth was observed was transplanted into an MBC medium containing no test compound, and re-cultured for 48 hours in the same manner to determine MBC. As the medium for MBC, SCDLP (SOYBEAN-CASEIN DIGEST BROTH with LECITHIN & POLYSORBATE 80) medium was used.
The lower the concentration of MIC and MBC, the stronger the antibacterial activity of the test compound and the better the antibacterial property.

<Method for evaluating skin irritation>
Using the antibacterial agent of the present invention and the comparative antibacterial agent shown in Table 1 as test compounds, skin irritation was evaluated by a patch test. A 10% aqueous solution of the test compound was prepared, and 100 mg was applied to the gauze part of the adhesive bandage for patch test and attached to the back side of the upper arm part. After 48 hours, the adhesive bandage was peeled off and left for 3 hours, and then the presence or absence of erythema was visually observed. The test was conducted on 10 men and women, and the evaluation was performed according to the following criteria.

Evaluation criteria A: There was no person with erythema.
B: One person had erythema.
C: Two people had erythema.
D: There were 3 or more people with erythema.

Claims (4)

An antibacterial agent comprising a quaternary ammonium salt represented by the general formula (1).

(In the formula, R ¹ is a hydrocarbon group having 6 to 24 carbon atoms, R ² is a hydrocarbon group having 1 to 24 carbon atoms, and R ³ is a hydrocarbon optionally substituted with a hydroxy group having 1 to 5 carbon atoms. Group, R ⁴ and R ⁵ each independently represents an alkylene group having 2 to 6 carbon atoms, n represents a number of 0.3 to 20 indicating the average number of added moles of the oxyalkylene group, and m represents an average of the oxyalkylene group. the number of 0.3 to 10 indicating the number of added moles, p is an integer of 1 to 3, q is 1 or 2, r and s are each independently an integer of 0 to 2, is p + q + r + s = 4 .A - Represents an anion.) In the general formula (1), p is 1, R ¹ is an aliphatic hydrocarbon group having 10 to 22 carbon atoms, R ² is an alkyl group having 1 to ³ carbon atoms, and R ³ is a hydroxy group having 1 to ³ carbon atoms. An aliphatic hydrocarbon group which may be substituted with R ⁴ and R ⁵ are each independently an alkylene group having 2 to 4 carbon atoms, n is a number of 0.5 to 10 and m is a number of 0.5 to 5 The antibacterial agent according to claim 1, wherein q is 1 or 2, r is 0 or 1, and s is 1. In the general formula (1), p is 2, R ¹ is an aliphatic hydrocarbon group having 8 to 16 carbon atoms, R ² is an alkyl group having 1 to ³ carbon atoms, and R ³ is a hydroxy group having 1 to ³ carbon atoms. An aliphatic hydrocarbon group which may be substituted with R ⁴ and R ⁵ are each independently an alkylene group having 2 to 4 carbon atoms, n is a number of 0.5 to 10 and m is a number of 0.5 to 5 The antibacterial agent according to claim 1, wherein q is 1, r is 0, and s is 1.   The antibacterial composition containing the antibacterial agent of any one of Claims 1-3.