JP2000256107A - Antimicrobial agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antimicrobial agent, harmless to humans, free from any problem related to safety sanitation or odor, and capable of exhibiting excellent antimicrobial effects over a wide pH range. SOLUTION: This antimicrobial agent contains, as an active ingredient, a sorbate ester shown by the formula CH3CH=CHCH=CHCOOR (R is a 1-10C alkyl, 7-16C aralkyl, 1-10C hydroxyl-substituted alkyl or 7-16C hydroxyl- substituted aralkyl).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an antibacterial agent.
More specifically, the present invention relates to an antibacterial agent that can exhibit excellent antibacterial properties in a wide pH range without any problems on human health and safety and odor.

[0002]

2. Description of the Related Art Conventionally, sorbic acid and its salts have been known to have very low toxicity and have a broad antibacterial spectrum against aerobic bacteria, yeasts, molds and the like, and are used as preservatives and preservatives. Has been approved by the Food Sanitation Law and is widely used in fish paste products, meat products, dried seafood products, boiled beans, tsukudani, fruit wine, etc. However, sorbic acid is a lower carboxylic acid and has a unique odor, and sorbic acid and its salts are positive for human skin irritation and skin sensitization. Furthermore, sorbic acid and its salts have a high antibacterial activity in a low pH range, but become dissociated in an alkaline range, and the antibacterial effect is drastically reduced. For this reason, sorbic acid compounds have not been developed for uses other than food additives. In recent years, problems such as environmental pollution due to chemical substances have been highlighted, and the safety of chemical substances to the environment and humans has been questioned. As for antibacterial agents, drugs that are even more safe have been required.

[0003]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an antibacterial agent which can exhibit excellent antibacterial properties in a wide pH range without problems of safety and hygiene to human body and odor. It was done.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, it has been found that sorbate compounds have low skin irritation, low odor, and antibacterial properties in a wide pH range. The inventors have found that the present invention has an effect, and have completed the present invention based on this finding. That is, the present invention provides: (1) an antibacterial agent comprising a sorbic acid ester represented by the general formula [1] as an active ingredient: CH ₃ CH = CHCH = CHCOOR (1) , R is an alkyl group having 1 to 10 carbon atoms, an aralkyl group having 7 to 16 carbon atoms, an alkyl group having 1 to 10 carbon atoms, or an aralkyl group having 7 to 16 carbon atoms.) To provide. Further, as a preferred embodiment of the present invention, (2) R
Is an antibacterial agent according to item (1), which is a monohydroxyalkyl group having 1 to 10 carbon atoms, and (3) an antibacterial agent wherein R is 2-hydroxyethyl group or 2-hydroxypropyl group.
The antibacterial agents described in (2) can be mentioned.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The antibacterial agent of the present invention has the general formula [1]
The sorbic acid ester represented by the following formula is contained as an active ingredient. CH ₃ CH = CHCH = CHCOOR [1] In the general formula [1], R represents an alkyl group having 1 to 10 carbon atoms, an aralkyl group having 7 to 16 carbon atoms, and 1 carbon atom.
10 to 10 hydroxyl-substituted alkyl groups or 7 to 7 carbon atoms
16 hydroxyl-substituted aralkyl groups. In the present invention, the alkyl group having 1 to 10 carbon atoms includes a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group,
Examples include a hexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group. These alkyl groups may be linear or branched. Examples of the aralkyl group having 7 to 16 carbon atoms include a benzyl group, a phenethyl group, a naphthylmethyl group, and a naphthylethyl group. Examples of the hydroxyl group-substituted alkyl group having 1 to 10 carbon atoms include a hydroxymethyl group, a 2-hydroxyethyl group, a 2-hydroxypropyl group, a 4-hydroxybutyl group, a 2,3-dihydroxypropyl group, and a 2,2- Dihydroxymethylpropyl group, 2,2-dihydroxymethylbutyl group, 2,2-dihydroxymethyl-3-hydroxypropyl group, 2,2,
6,6-tetrahydroxymethyl-7-hydroxy-4
-Oxaheptyl groups, residues of polyvinyl alcohol oligomers, and the like. Examples of the hydroxyl-substituted aralkyl group having 7 to 16 carbon atoms include, for example, 4-
Examples include a hydroxybenzyl group, a 2,6-dihydroxybenzyl group, a 4-hydroxyphenethyl group, a 5-hydroxynaphthylmethyl group, and a 6-hydroxynaphthylethyl group. Among these, sorbic acid-2-hydroxyethyl ester wherein R is a 2-hydroxyethyl group or a 2-hydroxypropyl group, and sorbic acid-
Since 2-hydroxypropyl ester has strong antibacterial performance, it can be particularly preferably used.

In the present invention, the method for producing the sorbic acid ester represented by the general formula [1] is not particularly limited. For example, dehydration esterification of sorbic acid and alcohol, dehydrohalogenation reaction of sorbic halide and alcohol And esterification by transesterification between a lower alcohol ester of sorbic acid and an alcohol. Further, an addition reaction between sorbic acid and a cyclic ether such as an oxirane compound can produce a sorbic acid ester represented by the general formula [1] in which R is a hydroxyl-substituted alkyl group. R is 2-
The sorbic acid ester represented by the general formula [1], which is a hydroxyethyl group or a 2-hydroxypropyl group, can be easily produced by an addition reaction of ethylene oxide or propylene oxide to sorbic acid. In this case, even if an excessive amount of ethylene oxide or propylene oxide is used relative to sorbic acid, unreacted ethylene oxide or propylene oxide can be easily removed after the reaction is completed. Hydroxyethyl ester and sorbic acid-2-
Hydroxypropyl ester can be obtained with high purity and high yield. There is no particular limitation on the form of the antibacterial agent of the present invention, and for example, it can be in a liquid or solid state. There is no particular limitation on the method of converting the antimicrobial agent of the present invention into a liquid state,
For example, the sorbic acid ester represented by the general formula [1] can be dissolved in various organic solvents to obtain a liquid state,
Alternatively, it can be emulsified or dispersed in water or an organic solvent using a surfactant, an emulsifier, or the like, and the emulsion or dispersion can be used as an antibacterial agent. The organic solvent in which the sorbate represented by the general formula [1] is dissolved or dispersed is not particularly limited, and examples thereof include lower alcohols such as ethanol and propanol, ketones such as acetone and methyl ethyl ketone, and esters such as ethyl acetate and methyl acetate. And the like. When emulsifying or dispersing the sorbic acid ester represented by the general formula [1], there is no particular limitation on the surfactant used, and examples thereof include polyoxyalkylene alkyl ether, polyoxyalkylene alkylphenyl ether, and polyoxyalkylene fatty acid ester. And anionic surfactants such as polyoxyalkylene alkyl ether sulfonate and polyoxyalkylene styrenated phenyl ether sulfonate.

The antibacterial agent of the present invention can be added to products requiring antibacterial properties and preservative properties, such as foods and various industrial products, to effectively suppress the growth of bacteria, fungi, protozoa and the like. it can. Further, since the antibacterial agent of the present invention does not cause discoloration even when applied to textiles, it can be suitably applied to textiles composed of white or light-colored dyed products. Sorbic acid, which has been conventionally recognized as a food additive, exhibits high antibacterial activity in a low pH range, but becomes dissociated in an alkaline range, and its antibacterial effect is drastically reduced. The sorbic acid ester used in the present invention does not dissociate even in an alkaline region, and exhibits an excellent antibacterial effect over all pH regions. Further, the sorbic acid ester used in the present invention, unlike sorbic acid, has no skin irritation or skin sensitization to humans, and therefore can be used safely.

[0008]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention. In Examples and Comparative Examples, antibacterial tests were performed according to the following methods. (1) Test bacteria Staphylococcus aureus (abbreviation S. aureus), Escherichia col
i (abbreviation E. coli), Klebsiellanapne
umoniae (abbreviation K. pneumoniae), P
pseudomonas aeruginosa (abbreviation P. aeruginosa), Serratia ma
rcescens (abbreviation S. marcescens) and Proteus vulgaris (abbreviation P. vul)
garris) were used as test bacteria. (2) Preparation of Test Bacterial Solution One platinum loop of the test bacterium was inoculated into 8 ml of Soybean Casein Digest (SCD) medium, cultured at 37 ° C. for 18 hours, and 1 ml of the culture was diluted 10-fold with SCD medium. . Further, 2 ml of this diluted solution was inoculated into 100 ml of SCD medium, and P. aeruginosa was cultured for 4 hours, and the other 5 types of test bacteria were cultured for 2 hours to obtain test bacterial solutions. The test bacterial solution contains 10 ⁷ to 10 ⁸ viable cells per ml. (3) Operation method 10 parts by weight of an antibacterial agent is dissolved in a mixture of 30 parts by weight of dimethyl sulfoxide and 70 parts by weight of distilled water, and then, using acetic acid or sodium bicarbonate, pH 3.9, pH 6.5 and pH.
To 10 ml of the solution adjusted to 9.8, 0.1 ml of each test bacterial solution was added and mixed. After contacting the bacteria with the antibacterial agent for 1 hour, 0.1 ml of the contact solution was added to each of 10 ml of SCD-lecithin & polysorbate 80 diluted (LP diluted) medium and mixed. After this was cultured at 37 ° C. for 24 hours, the minimum bactericidal concentration (MBC) was determined based on whether or not the medium was turbid. Example 1 (Synthesis of sorbic acid-2-hydroxyethyl ester) Sorbic acid 20 g (0.18 mol), tetramethylammonium chloride 0.1 g and isopropanol 10
After heating 0 ml of the mixture to 100 ° C. in an autoclave, 11 g of ethylene oxide (0.25 mol)
Was added and stirred at 100 ° C. for 5 hours. After the reaction is completed, isopropanol and unreacted ethylene oxide are removed,
The reaction product was further washed with water to obtain 25.6 g of sorbic acid-2-hydroxyethyl ester. The resulting sorbic acid-
The acid value of 2-hydroxyethyl ester was 0.2 or less. Example 2 (Synthesis of sorbic acid-2-hydroxypropyl ester) 20 g (0.18 mol) of sorbic acid, 0.1 g of tetramethylammonium chloride and 10 g of isopropanol
After heating 0 ml of the mixture to 100 ° C. in an autoclave, 14.5 g (0.25 mol) of propylene oxide was added, and the mixture was stirred at 100 ° C. for 5 hours. After the reaction,
Isopropanol and unreacted propylene oxide were removed, and the reaction product was washed with water to obtain 28.3 g of sorbic acid-2-hydroxypropyl ester. The acid value of the obtained sorbic acid-2-hydroxypropyl ester is 0.2.
It was below.

Example 3 (Antibacterial test of sorbic acid-2-hydroxyethyl ester) An antibacterial test was conducted using sorbic acid-2-hydroxyethyl ester as an antibacterial agent. When the pH is 3.9, the minimum bactericidal concentration is 2,5 for Aureus
00 μg / ml; 2,000 μg / m for E. coli
l, K. 1,500 μg / m to pneumoniae
l, p. 1,500 μg / m against aeruginosa
l, S. 2,500 μg / m for Marcescens
l, p. vulgaris, 2500 μg / ml. When the pH is 6.5, the minimum germicidal concentration is a
ureus, 2500 μg / ml; 2,500 μg / ml against K. coli. 1,500 μg / ml against P. pneumoniae; aeruginosa, 1500 μg / ml; 2,500 μg / ml for P. marcescens; vulgaris, 2500 μg / ml. When the pH is 9.8, the minimum germicidal concentration is 2500 μg for Aureus
/ Ml, E.C. 2,500 μg / ml against K. coli. p
1,500 μg / ml against P. neumoniae; a
eruginosa, 1500 μg / ml; m
2,500 μg / ml vs. P. arcescens. v
ulgaris, 2,500 μg / ml. Example 4 (Antibacterial test of sorbic acid-2-hydroxypropyl ester) An antibacterial test was performed using sorbic acid-2-hydroxypropyl ester as an antibacterial agent. When the pH is 3.9, the minimum bactericidal concentration is aureus 2,
500 μg / ml, E. 2,000 μg / m for E. coli
l, K. 1,500 μg / m to pneumoniae
l, p. 1,500 μg / m against aeruginosa
l, S. 2,500 μg / m for Marcescens
l, p. vulgaris, 2500 μg / ml. When the pH is 6.5, the minimum germicidal concentration is a
ureus, 2500 μg / ml; 2,000 μg / ml against K. coli. 1,500 μg / ml against P. pneumoniae; aeruginosa, 1500 μg / ml; 2,500 μg / ml for P. marcescens; vulgaris, 2500 μg / ml. When the pH is 9.8, the minimum germicidal concentration is 2500 μg for Aureus
/ Ml, E.C. 2,000 μg / ml against K. coli. p
1,500 μg / ml against P. neumoniae; a
eruginosa, 1500 μg / ml; m
2,500 μg / ml vs. P. arcescens. v
ulgaris, 2,500 μg / ml. Comparative Example 1 (Antibacterial test of sorbic acid) An antibacterial test was conducted using sorbic acid as an antibacterial agent. When the pH is 3.9, the minimum bactericidal concentration is au
2,500 μg / ml for E. reus; 2,500 μg / ml against K. coli. 1,500 μg / ml against P. pneumoniae; aeruginosa, 1500 μg / ml; 2,500 μg / ml for P. marcescens; vulgaris 2,
It was 500 μg / ml. When the pH is 6.5, the minimum germicidal concentration is 2,500 μg / m for Aureus
l, E. 2,500 μg / ml against K. coli. pne
umoniae, 1,500 μg / ml, P. aer
uginosa, 1500 μg / ml; mar
2,500 μg / ml against P. cescens; vul
2,500 μg / ml for garis. pH 9.
8, the minimum bactericidal concentration is S.P. aureus,
E. FIG. coli, K.E. pneumoniae, P .; aer
uginosa, S .; marcescens and P.M. v
10,000 μg / ml for all of ulgaris
That was all. Table 1 shows the results of Examples 3 and 4 and Comparative Example 1.

[0010]

[Table 1]

As shown in Table 1, sorbic acid-2
Examples 3 and 4 using -hydroxyethyl ester or sorbic acid-2-hydroxypropyl ester
, The minimum bactericidal concentration is low at pH 3.9 to 9.8, indicating that the antibacterial agent of the present invention exhibits an excellent antibacterial effect in a wide pH range. On the other hand, in Comparative Example 1 using sorbic acid, the pH was 3.9 and 6.5.
Has a minimum bactericidal concentration equivalent to that of Examples 3 and 4,
At 9.8, the minimum germicidal concentration sharply increases, indicating that sorbic acid has a drastically reduced antibacterial effect in the alkaline region.

[0012]

The antibacterial agent of the present invention contains, as an active ingredient, a nonionic compound obtained by esterifying sorbic acid as an active ingredient. No, exhibits excellent antibacterial effect in a wide pH range.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Kimihiro Makino 4-23-1, Bunkyo, Fukui City, Fukui Prefecture F-term in Nichika Chemical Co., Ltd. 4H011 AA01 AA02 AA03 BB06 DD07

Claims (1)

[Claims] An antibacterial agent comprising a sorbic acid ester represented by the general formula [1] as an active ingredient. CH ₃ CH ＝ CHCH ＝ CHCOOR [1] (wherein, R is an alkyl group having 1 to 10 carbon atoms, an aralkyl group having 7 to 16 carbon atoms, a hydroxyl group-substituted alkyl group having 1 to 10 carbon atoms or carbon atom It is a hydroxyl-substituted aralkyl group of the number 7 to 16.)