JP2005120060A - Agent for increasing antibacterial activity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a compound effective for increasing the antibacterial activity of organic antibacterial agents and usable without froming bacteria having acquired resistivity/resistance even after the use at a low concentration for a long period. <P>SOLUTION: The agent for improving antibacterial activity contains a quaternary ammonium salt compound expressed by formula (1) (R<SB>1</SB>and R<SB>4</SB>are each a 6-16C alkyl which may have branches; R<SB>2</SB>and R<SB>5</SB>are each a 1-4C hydroxy-containing alkyl; R<SB>3</SB>and R<SB>6</SB>are each a 1-4C alkyl or a 1-4C hydroxy-containing alkyl; X<SP>n-</SP>is an inorganic or organic anion group; n is the valence of the anion group X<SP>n-</SP>and is 1 or 2; and m is 2 when n is 1 and is 1 when n is 2). The invention further provides an antibacterial formulation containing the antibacterial activity increasing agent. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a compound that enhances antibacterial activity by blending with an antibacterial agent.

  Organic antibacterial agents have been known for a long time and are widely used as antibacterial agents even today because of their high antibacterial effect against bacteria and immediate effects. As an organic antibacterial agent, a great many kinds of compounds such as amine compounds, alcohol compounds, aldehyde compounds and halogen compounds, carboxylic acid compounds and phenol compounds, quaternary ammonium salt compounds, amphoteric surfactants, biguanide compounds and isothiazoline compounds Is known and widely used. The following are typical examples.

  Quaternary ammonium salt compounds such as benzalkonium chloride, benzethonium chloride, didecyldimethylammonium chloride, amphoteric surfactants such as alkylpolyaminoethylglycine and alkyldiaminoethylglycine, biguanide compounds such as chlorhexidine gluconate, 2,2 -Organic bromine antibacterial agents such as dibromo-3-nitrilopropionamide and bis-1,4-bromoacetoxy-2-butene.

  However, when organic antibacterial agents are used repeatedly, the bacteria acquire resistance to these antibacterial agents and the antibacterial effect decreases. Moreover, although it may mix | blend and use with another antibacterial agent, it was not able to inhibit the acquisition of the resistance of a microbe to an antibacterial agent. That is, when an organic antibacterial agent is used for a long period of time, the bacteria acquire resistance / resistance and become difficult to use.

  An object of the present invention is to provide a compound which can enhance the antibacterial activity of an organic antibacterial agent and can be used at a low concentration and without acquiring resistance / resistance to bacteria even when used for a long time.

As a result of intensive studies, the inventor has found that the problem can be solved by using a quaternary ammonium salt compound of the following formula (1), and has completed the present invention. That is, the present invention is an antibacterial activity enhancer using a quaternary ammonium salt compound represented by the following formula (1). Moreover, it is an antibacterial compounding agent containing the said antibacterial power enhancer.

In Formula (1), R ₁ is an alkyl group having 6 to 16 carbon atoms that may be branched, R ₂ is an alkyl group having 1 to 4 carbon atoms having a hydroxyl group, and R ₃ is 1 carbon atom. An alkyl group having 1 to 4 carbon atoms or a hydroxyl group having 1 to 4 carbon atoms, R ₄ is an optionally branched alkyl group having 6 to 16 carbon atoms, and R ₅ is a carbon number having a hydroxyl group. An alkyl group having 1 to 4 carbon atoms, R ₆ is an alkyl group having 1 to 4 carbon atoms or an alkyl group having 1 to 4 carbon atoms having a hydroxyl group, and X ⁿ⁻ is an inorganic or organic anionic group. , N is the valence of the anionic group X ^n- and is selected from either 1 or 2, m is 2 when n is 1 and 1 when n is 2.

  The antibacterial activity enhancer of the present invention has a function of enhancing the antibacterial activity of the antibacterial agent. From this, the antibacterial compounding agent which mix | blended the antibacterial power enhancer of this invention can be used in low concentration. In addition, antibacterial agents, when used for a long period of time, will emerge strains that are resistant to antibacterial agents (resistant bacteria). can do.

  The present invention uses the quaternary ammonium salt compound represented by the above formula (1) as an antibacterial activity enhancer. Compared to those using organic antibacterial agents other than those of formula (1) alone, the compounded ones show antibacterial activity at a low concentration and can inhibit the bacteria from acquiring resistance to organic antibacterial agents. is there. Hereinafter, the present invention will be described in detail.

  The present invention is an antibacterial activity enhancer using a quaternary ammonium salt compound represented by the above formula (1), and the antibacterial activity enhancer as compared with those using an organic antibacterial agent other than the formula (1) alone. In the case of blending, the antibacterial activity is exhibited at a low concentration, and it is possible to prevent the bacteria from acquiring resistance to the organic antibacterial agent. Therefore, the antibacterial compounding agent in which the antibacterial activity enhancer of the present invention is blended can be used for a long period of time and requires a small amount of the organic antibacterial agent. The organic antibacterial agent is hereinafter referred to as an antibacterial agent.

X ^{n− in the} above formula (1) is an inorganic or organic anion group, preferably iodine ion, bromine ion, chlorine ion, fluorine ion, iodate ion, bromate ion, chlorate ion, periodate Acid ion, perchlorate ion, chlorite ion, hypochlorite ion, nitrate ion, nitrite ion, sulfate ion, hydroxide ion or anion group represented by the following formulas (2) to (5) More preferred are iodine ion, bromine ion and chlorine ion.
The number (m) of the anion group X bonded to the compound of the formula (1) is a number where the product of n and m is 2 when the valence of the anion group X ⁿ⁻ is n. When the group X ^n- is divalent, it is 1, and when it is monovalent, it is 2.

R ₇ COO ^- (2)
Wherein (2), R ₇ is an alkyl group or an alkenyl group having 2 to 7 carbon atoms carbon atoms 1 to 7 have a hydroxyl group or a carbonyl group.

^{_{- OOC- (R 8) P -COO}} - (3)
In formula (3), p is 0 or 1, and when p is 1, R ₈ is an alkyl group having 1 to 8 carbon atoms or an alkenyl group having 2 to 7 carbon atoms which may have a hydroxyl group.

R ₉ SO ₄ ^- ₍₄₎
In formula (4), R ₉ represents an alkyl group having 1 to 16 carbon atoms.

In Formula (5), R ₁₀ and R ₁₁ each represent a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or a carboxyl group.

The antibacterial activity enhancer of the present invention has an activity of enhancing the antibacterial activity against antibacterial agents other than the formula (1). From this, the antibacterial compounding agent containing the antibacterial activity enhancer of the present invention can be used at a lower concentration than the antibacterial agent alone.
In addition, when an antibacterial agent is used for a long period of time, bacteria acquire resistance and resistance, but the antibacterial compounding agent containing the antibacterial activity enhancer of the present invention does not have such a problem. From this, the antibacterial compounding agent compounded with the compound of the formula (1) of the present invention does not worry about the emergence of a strain having resistance and resistance compared to the antibacterial compounding agent compounded with a compound other than the formula (1). Can be used for a long time.

  The antibacterial activity enhancer of the present invention can be used in combination with an antibacterial agent other than the formula (1). As this antibacterial agent, amine compound antibacterial agent, alcohol compound antibacterial agent, aldehyde compound antibacterial agent, halogen compound antibacterial agent, carboxylic acid compound antibacterial agent, phenol compound antibacterial agent, quaternary ammonium salt compound antibacterial agent Agent, amphoteric surfactant antibacterial agent, biguanide compound antibacterial agent, isothiazoline compound antibacterial agent, beta-lactam antibiotic or quinolone synthetic antibacterial agent. Preferred antibacterial agents include benzalkonium chloride, quaternary ammonium salt compounds such as benzethonium chloride and didecyldimethylammonium chloride, amphoteric surfactants such as alkylpolyaminoethylglycine and alkyldiaminoethylglycine, and chlorhexidine gluconate. And the like, and organic bromine antibacterial agents such as 2,2-dibromo-3-nitrilopropionamide and bis-1,4-bromoacetoxy-2-butene. Tetraammonium salt compounds, biguanide compounds, and organic bromine antibacterial agents are preferred, and quaternary ammonium salt compounds are particularly preferred.

  The antibacterial activity enhancer of the present invention is a compound represented by the formula (1). In the above formula (1), the position where the quaternary ammonium salt is bonded to biphenyl may be any, but the 4,4 ′ position is preferred. .

In the antibacterial activity enhancer of the present invention, R ₁ and R _{4 in} the formula (1) may be different and are preferably the same. R ₂ and R ₅ may be different and are preferably the same. R ₃ and R ₆ may be different and are preferably the same. The number of hydroxyl groups possessed by this compound is 1 to 4, preferably 2 to 4, and more preferably 4. The alkyl group of formula (1) may be branched, but is preferably a straight chain.

R ₁ and R ₄ of the antibacterial activity enhancer represented by the formula (1) of the present invention are an alkyl group having 4 to 20 carbon atoms, and preferably an alkyl group having 6 to 16 carbon atoms which may be branched. More preferably, it is a linear alkyl group having 8 to 14 carbon atoms, particularly preferably an even number.

R ₂ of the antibacterial activity enhancer represented by the formula (1) of the present invention is an alkyl group having 1 to 4 carbon atoms having a hydroxyl group, preferably an alkyl group having 2 to 4 carbon atoms having a hydroxyl group. More preferably an alkyl group having 2 carbon atoms having a hydroxyl group, and a 2-hydroxyethyl group.

R ₅ of the antibacterial activity enhancer represented by the formula (1) of the present invention is a C 1-4 alkyl group having a hydroxyl group, preferably a C 2-4 alkyl group having a hydroxyl group. More preferably an alkyl group having 2 carbon atoms having a hydroxyl group, and a 2-hydroxyethyl group. R ₂ and R ₅ may be different but are preferably the same.

R ₃ of the antibacterial activity enhancer represented by the formula (1) of the present invention is a C 1-4 alkyl group having a hydroxyl group or a C 1-4 alkyl group, preferably having a hydroxyl group. It is a C2-C4 alkyl group or a C1-C2 alkyl group, More preferably, it is a C2-C2 alkyl group or a methyl group which has a hydroxyl group, and is 2-hydroxyethyl group.

R ₆ of the antibacterial power enhancer represented by the formula (1) of the present invention is a C 1-4 alkyl group having a hydroxyl group or a C 1-4 alkyl group, preferably having a hydroxyl group. It is a C2-C4 alkyl group or a C1-C2 alkyl group, More preferably, it is a C2-C2 alkyl group or a methyl group which has a hydroxyl group, and is 2-hydroxyethyl group. R ₃ and R ₆ may be different but are preferably the same. Furthermore, it is more preferable that R ₂ , R ₃ , R ₅ and R ₆ are all the same.

  The blending ratio of the antibacterial force enhancer of the present invention in the antibacterial compounding agent is preferably 1 to 80 parts by mass, preferably 5 to 60 parts by mass with respect to 100 parts by mass of the antibacterial agent in the antibacterial compounding agent. Part is more preferable, and 10 to 50 parts by mass is particularly preferable.

  The antibacterial compounding agent of the present invention can be used by appropriately supporting it on a solid or liquid carrier. In addition, the antibacterial compounding agent of the present invention can be used as an emulsion, a wettable powder, a granule, a powder, a spray, an aerosol and the like by blending other components such as a surfactant as necessary. As this surfactant, nonionic surfactants such as polyoxyethylene alkyl ether and amphoteric surfactants such as alkyl (amido) betaine can be used. As a specific example, what added benzalkonium chloride and / or polyhexamethylene biguanide to the compound represented by Formula (1) and polyoxyethylene alkyl ether can be used as an antibacterial agent or a cleaning agent. Moreover, what added benzalkonium chloride and / or polyhexamethylene biguanide to the compound represented by Formula (1) and alkylamide betaine can be used as an antibacterial agent or a cleaning agent.

The antibacterial compounding agent of the present invention can be used in a wide range of fields. For example, antibacterial and deodorized textile products, leather products, building materials, wood, paints, adhesives, plastics, films, paper, pulp, metalworking oils, foods, pharmaceuticals, medical / environmental disinfectants, ophthalmic treatments, contact care products It is useful in eye drops, detergents, cosmetics, stationery, agricultural chemicals, livestock fields, and the like. For example, it can be used as a disinfectant or cleaning agent for facilities and equipment in food factories and drinking water factories.
The compound represented by the formula (1) can be blended with a surfactant and used as an antibacterial agent or a cleaning agent. As the surfactant at this time, a nonionic surfactant such as polyoxyethylene alkyl ether or an amphoteric surfactant such as alkyl (amido) betaine can be used. As a specific example, it can be used as an antibacterial agent or cleaning agent comprising a compound represented by the formula (1) and polyoxyethylene alkyl ether. Moreover, it can be used as an antibacterial agent and a cleaning agent by the compound represented by Formula (1) and alkylamide betaine.

<Example>
EXAMPLES Hereinafter, although an Example and a comparative example demonstrate this invention further more concretely, this invention is not limited to this. The unit of MIC in each table is μg / ml.

<Synthesis Example 1>
After adding 5.02 mmol of 4,4′-bis (chloromethyl) biphenyl and 12.5 mmol of N, N-bis (2-hydroxyethyl) decylamine to 15 ml of acetonitrile, the mixture is reacted for 24 hours under heating and refluxing, and then precipitated. The solid was filtered and collected. The collected solid was washed with ethyl acetate, recrystallized with a mixed solution of ethanol / ethyl acetate, and dried under reduced pressure to give white 4,4′-bis (N, N-bis (2-hydroxyethyl) -N-decyl. 6.08 g of ammoniomethyl) biphenyl dichloride (abbreviated as 4B2OH-10) was obtained. The yield of the target compound was 82%.
The melting point was 187-190 ° C.
The results of ¹ H-NMR (solvent DMSO-d ₆ ) analysis of 4B2OH-10 are shown below.
δ (ppm): 7.88 (4H, d, J = 8.2 Hz) 7.74 (4H, d, J = 8.2 Hz) 5.57 (4H, t, J = 5.2 Hz) 4.78 (4H, s) 3.95 (8H, m) 3.42 (8H, m) 3.28 (4H, m) 1.82 (4H, m) 1.26 (28H, m) 0.86 (6H , T, J = 6.8 Hz).
Further the results of elemental analysis in the following (the molecular formula 4B2OH-10 is _{C 42 H 74 Cl 2 N 2} O 4).
Carbon Hydrogen Nitrogen Theoretical value (%) 69.99 10.15 3.78
Actual value (%) 67.64 10.08 3.85
From the above results, it was confirmed that the obtained substance was the target compound.

<Synthesis Example 2>
4,4′-bis (chloromethyl) biphenyl (1.26 g, 5.02 mmol) and N, N-bis (2-hydroxyethyl) octylamine (2.73 g, 12.5 mmol) were added to 15 ml of ethanol, After reacting for 12 hours while heating under reflux, the solvent ethanol was removed under reduced pressure. The residue was washed with ethyl acetate, recrystallized with a mixed solution of acetonitrile / ethyl acetate, and dried under reduced pressure to give white 4,4′-bis (N, N-bis (2-hydroxyethyl) -N-octylammonio. 3.44 g of methyl) biphenyl dichloride (abbreviated as 4B2OH-8) was obtained. The yield of the target compound was 91%.

The result of ¹ H-NMR (solvent DMSO-d ₆ ) analysis of 4B2OH-8 is shown below.
δ (ppm): 7.88 (4H, d, J = 8.0 Hz), 7.74 (4H, d, J = 8.0 Hz), 5.60 (4H, t), 4.79 (4H, s), 3.95 (8H, m), 3.42 (8H, m), 3.34 (4H, m), 1.82 (4H, m), 1.27 (20H, m),. 86 (6H, t, J = 6.8 Hz).

The results of elemental analysis are shown below (the molecular formula of 4B2OH-8 is C ₃₈ H ₆₆ Cl ₂ N ₂ O ₄ ).
Carbon Hydrogen Nitrogen Theoretical value (%) 66.55 9.70 4.08
Actual value (%) 66.20 9.66 4.17
From the above results, it was confirmed that the obtained substance was the target compound.

<Synthesis Example 3>
4,4′-bis (chloromethyl) biphenyl (1.50 g = 5.97 mmol) and N, N-bis (2-hydroxyethyl) dodecylamine (4.10 g = 14.6 mmol) were added to 10 ml of isopropyl alcohol. The mixture was reacted for 10 hours under heating and reflux, and then the solvent isopropanol was removed under reduced pressure. The residue was washed with ethyl acetate, recrystallized from a mixed solution of acetonitrile / ethyl acetate, and dried under reduced pressure to give white compound 4,4′-bis (N, N-bis (2-hydroxyethyl) -N-dodecylammonio. 4.05 g of methyl) biphenyl dichloride (abbreviated as 4B2OH-12) was obtained. The yield of the target compound was 85%.

The results of ¹ H-NMR (solvent DMSO-d ₆ ) analysis of 4B2OH-12 are shown below.
δ (ppm): 7.88 (4H, d, J = 8.4 Hz), 7.74 (4H, d, J = 8.4 Hz), 5.60 (4H, t), 4.79 (4H, s), 3.94 (8H, m), 3.41 (8H, m), 3.29 (4H, m), 1.82 (4H, m), 1.25 (36H, m),. 86 (6H, t, J = 6.8 Hz).
From the above results, it was confirmed that the obtained substance was the target compound.

<Synthesis Example 4>
10 ml of 4,4′-bis (chloromethyl) biphenyl (1.52 g = 6.05 mmol) and N- (2-hydroxyethyl) -N-methyl-N-octylamine (2.84 g = 15.2 mmol) Added to isopropanol and refluxed for 2 hours. The reaction solution was returned to room temperature, the solvent isopropanol was removed under reduced pressure, and the residue was washed with ethyl acetate to obtain crude crystals. The crude crystals were recrystallized from a chloroform / ethyl acetate mixed solution and dried under reduced pressure to give white 4,4′-bis (N- (2-hydroxyethyl) -N-methyl-N-octylammoniomethyl) biphenyl dichloride. 3.41 g (abbreviated as 4B1OH-8) was obtained. The yield of the target compound was 90%.

The result of ¹ H-NMR (solvent DMSO-d ₆ ) analysis of 4B1OH-8 is shown below.
δ (ppm): 7.88 (4H, d, J = 8.0 Hz), 7.73 (4H, d, J = 8.0 Hz), 5.64 (2H, t, J = 5.2 Hz), 4.71 (4H, dd, J = 12.8 Hz), 3.92 (4H, m), 3.49-3.28 (8H, m), 3.02 (6H, s), 1.80 ( 4H, m), 1.30-1.27 (20H, m), 0.87 (6H, t, J = 6.8 Hz).
From the above results, it was confirmed that the obtained substance was the target compound.

<Synthesis Example 5>
4,4′-bis (chloromethyl) biphenyl (1.56 g = 6.21 mmol) and N- (2-hydroxyethyl) -N-methyl-N-decylamine (3.39 g = 15.7 mmol) were added to 10 ml of isopropanol. And refluxed for 2 hours. The reaction solution was returned to room temperature, the solvent isopropanol was removed under reduced pressure, and the residue was washed with ethyl acetate to obtain crude crystals. The crude crystals were recrystallized from a chloroform / ethyl acetate mixed solution and dried under reduced pressure to give white 4,4′-bis (N- (2-hydroxyethyl) -N-methyl-N-decylammoniomethyl) biphenyl dichloride. 4.05 g (abbreviated as 4B1OH-10) was obtained. The yield of the target compound was 96%.
The results of elemental analysis are shown below (the molecular formula of 4B1OH-10 is C ₄₀ H ₇₀ Cl ₂ N ₂ O ₂ ).
Carbon Hydrogen Nitrogen Theoretical value (%) 70.45 10.35 4.11
Actual value (%) 70.08 10.28 4.30

The result of ¹ H-NMR (solvent DMSO-d ₆ ) analysis of 4B1OH-10 is shown below.
δ (ppm): 7.88 (4H, d, J = 8.4 Hz), 7.74 (4H, d, J = 8.4 Hz), 5.66 (2H, t, J = 5.2 Hz), 4.72 (4H, dd, J = 13.2 Hz), 3.92 (4H, m), 3.49-3.28 (8H, m), 3.02 (6H, s), 1.80 ( 4H, m), 1.26 (28H, m), 0.86 (6H, t, J = 6.8 Hz).
From the above results, it was confirmed that the obtained substance was the target compound.

<Synthesis Example 6>
4,4′-bis (chloromethyl) biphenyl (1.54 g = 6.13 mmol) and N- (2-hydroxyethyl) -N-methyl-N-dodecylamine (3.81 g = 15.7 mmol) in 10 ml Added to isopropanol and refluxed for 3 hours. The reaction solution was returned to room temperature, the solvent isopropanol was removed under reduced pressure, and the residue was washed with ethyl acetate to obtain crude crystals. The crude crystals were recrystallized from a chloroform / ethyl acetate mixed solution and dried under reduced pressure to give white 4,4′-bis (N- (2-hydroxyethyl) -N-methyl-N-dodecylammoniomethyl) biphenyl dichloride. 4.43 g (abbreviated as 4B1OH-12) was obtained. The yield of the target compound was 98%.
The result of ¹ H-NMR (solvent DMSO-d ₆ ) analysis of 4B1OH-12 is shown below.
δ (ppm): 7.88 (4H, d, J = 8.4 Hz), 7.73 (4H, d, J = 8.4 Hz), 5.64 (2H, t, J = 5.2 Hz), 4.71 (4H, dd, J = 12.8 Hz), 3.92 (4H, m), 3.49-3.28 (8H, m), 3.02 (6H, s), 1.80 ( 4H, m), 1.27 (36H, m), 0.87 (6H, t, J = 6.8 Hz).
From the above results, it was confirmed that the obtained substance was the target compound.

○ Comparative Example Compounds The following compounds were used as comparative compounds.
Benzalkonium chloride (manufactured by Wako Pure Chemical Industries): hereinafter abbreviated as BAC.
Didecyldimethylammonium bromide (Aldrich): hereinafter abbreviated as DDAB.
Chlorhexidine gluconate (manufactured by Wako Pure Chemical Industries, Ltd.): hereinafter abbreviated as CHG.
2,2-dibromo-3-nitrilopropionamide (manufactured by Suzhou Jinlong New Chemical Material Co., Ltd., China): hereinafter abbreviated as DBNPA.
Bis-1,4-bromoacetoxy-2-butene (manufactured by Suzhou Jinlong New Chemical Material Co., Ltd., China): hereinafter abbreviated as BBAB.

<Test Example 1>
○ Minimum inhibitory concentration against bacteria (MIC)
According to a general broth dilution method, a steady-state bacterial solution adjusted to a bacterial suspension concentration of 10 ⁶ cells / ml using a neutral broth was added to the serially diluted drug solution, After culturing for 24 hours, the MIC value was determined based on the presence or absence of proliferation.
Escherichia coli K12 W 3110 (referred to as E. coli) and Staphylococcus aureus IFO 12732 (referred to as S. aureus) were used as test bacteria. The results are shown in Table 1.

○ Activity against benzalkonium chloride (BAC) 4B2OH-10 of Synthesis Example 1 and benzalkonium chloride (BAC) are mixed at a mass ratio of 20:80, 40:60, 60:40, 80:20. did. About this mixed chemical | medical agent, 4B2OH-10, and benzalkonium chloride, operation similar to Test Example 1 was performed and the MIC value was measured.
As the test bacteria, those used in Test Example 1 were used. The results are shown in Table 2.

4B2OH-10 of Synthesis Example 1 and benzalkonium chloride (BAC) were mixed at a mass ratio of 40:60, 30:70, and 20:80. About this mixed chemical | medical agent, 4B2OH-10, and benzalkonium chloride, operation similar to Test Example 1 was performed and the MIC value was measured.
E. coli was used as a test bacterium. The results are shown in Table 3.

○ Activity against DDAB The same operation as in Example 1 was carried out except that DDAB was used instead of BAC, and the MIC value was measured. The results are shown in Table 4.

○ Activity against CHG The same operation as in Example 1 was carried out except that CHG was used instead of BAC, and the MIC value was measured. The results are shown in Table 5.

○ Activity against DBNPA The same operation as in Example 1 and Example 2 was performed except that DBNPA was used instead of BAC, and the MIC value was measured. The results are shown in Tables 6 and 7.

○ Activity against BBAB The same procedure as in Example 1 was carried out except that BBAB was used instead of BAC, and the MIC value was measured. The results are shown in Table 8.

  From the results of the above Examples (Tables 2 to 8), the MIC value of the mixture containing the compound of the present invention is smaller than that of the comparative compound alone. From this, it is clear that the antibacterial activity of the compound of the present invention is enhanced by mixing with the compound of the comparative example.

○ Minimum Growth Inhibitory Concentration (MIC) Change Test The test was performed using B2OH-10 of Synthesis Example 1 and BAC, DDAB, CHG, DBNPA, and BBAB mixed at a mass ratio of 30:70.
The test was performed according to the method for obtaining antibacterial agent-resistant bacteria. That is, using E. coli as a test bacterium, according to a general broth dilution method, a bacterial solution in a stationary phase adjusted to a bacterial suspension of 10 ⁶ cells / ml using a nutrient broth was prepared. , After adding to the serially diluted drug solution and standing at 37 ° C. for 24 hours, the minimum concentration of the test drug without turbidity is taken as the MIC value, and the bacteria in the test solution with a low one-step test compound concentration (ie, The following test bacterial solution was obtained using the test solution in which turbidity was observed. In this way, this operation was repeated 10 times.
Table 9 shows the results of MIC values for the first and tenth compounds.

○ MIC change test with compound alone B2OH-10, BAC, DDAB, CHG, DBNPA or BBAB were measured using the test method of Example 7, and the results of the MIC values at the first and tenth times are shown. 10 shows.

From the results shown in Table 10, when the compound for Comparative Example is kept in contact with bacteria at a concentration that does not kill, a strain whose MIC value rises twice or more appears. However, since the antibacterial activity enhancer of the present invention does not show an increase in the MIC value even when this operation is repeated, it indicates that no resistant strain appears.
Further, as can be seen from Tables 9 and 10, the antibacterial compounding agent formulated with the antibacterial activity enhancer of the present invention does not show a resistant strain even if the bacteria are kept in contact at a concentration that does not kill. This indicates that the antibacterial compounding agent containing the antibacterial activity enhancer of the present invention can be used continuously for a long period of time.

  The antibacterial activity enhancer represented by the formula (1) of the present invention has a function of enhancing the antibacterial activity of the antibacterial agent. From this, the antibacterial compounding agent which mix | blended the antibacterial power enhancer of this invention can be used in low concentration, and is industrially useful. In addition, antibacterial agents, when used for a long period of time, will emerge strains that are resistant to antibacterial agents (resistant bacteria). can do. From this, the antibacterial compounding agent containing the antibacterial activity enhancer of the present invention can be used at a low concentration and continuously for a long period of time, and is industrially useful.

Claims (3)

An antibacterial activity enhancer comprising a quaternary ammonium salt compound represented by the following formula (1) as an active ingredient.

In Expression (1), R ₁ is an alkyl group having 6 to 16 carbon atoms which may be a branched, R ₂ is an alkyl group having 1 to 4 carbon atoms having a hydroxyl group, R ₃ is the number of carbon atoms An alkyl group having 1 to 4 alkyl groups or a hydroxyl group having 1 to 4 carbon atoms, R ₄ is an optionally branched alkyl group having 6 to 16 carbon atoms, and R ₅ is a carbon having a hydroxyl group. An alkyl group having 1 to 4 carbon atoms, R ₆ is an alkyl group having 1 to 4 carbon atoms or an alkyl group having 1 to 4 carbon atoms having a hydroxyl group, and X ⁿ⁻ is an inorganic or organic anionic group. Yes, n is the valence of the anionic group X ^n- and is selected from either 1 or 2, m is 2 when n is 1 and 1 when n is 2. ]   An antibacterial compounding agent comprising the quaternary ammonium salt compound according to claim 1.   The quaternary ammonium salt compound according to claim 1 is contained in an amount of 1 to 80 parts by mass with respect to 100 parts by mass in total of the antibacterial agents in the antibacterial compounding agent.