JP5035554B2 - Antibacterial and antibacterial agents - Google Patents

Description

  The present invention relates to an antibacterial agent and an antibacterial agent which have an excellent antibacterial action, are highly safe and have almost no burden on the environment.

  In recent years, antibacterial agents using silver ions, antibacterial sprays, and the like have been developed, and antibacterial sheets to which organic compound-based antibacterial agents are added are widely used in daily life. However, there is a problem of toxicity with respect to silver ions, and there are currently limited substances or objects to be used for organic compound antibacterial agents from the viewpoint of safety.

  Among the antibacterial agents used in animal feed production and poultry farms to control microorganisms such as bacteria (for example, Salmonella), yeast, and mold, antibacterial agents including formic acid and propionic acid are known. The toxicity of formic acid and the unpleasant odor of propionic acid and formic acid have become operational problems. Further, since the pH is low, there is a possibility of corrosion of metals and the like.

  On the other hand, highly safe antibacterial agents derived from natural products are also known, but many have problems in cost and production methods. As antibacterial agents derived from natural products, antibacterial agents derived from citrus fruits are known (Patent Document 1). This is a compound obtained by refining the residue obtained by concentrating the essential oil obtained by pressing lemon peel, but the concentration must be adjusted to obtain the desired antibacterial agent. The law is cumbersome and not economical.

  Moreover, although the antibacterial agent containing the cloveranaenju extract of a leguminous plant is reported (patent document 2), a cloveranaenju is not a plant of a cultivation system, and since solvent extraction is required, it is not economical. The antibacterial agent described in Patent Document 3 uses gallic acid derived from tannin as in the present invention, but it is necessary to use a highly toxic substance such as crown ether.

Furthermore, as an active ingredient of the antibacterial agent, a ferulic acid ester compound made from natural ferulic acid as a raw material has also been reported (Patent Document 4), but ferulic acid itself obtained from rice bran is expensive and is an ester. The safety of the compound has not been confirmed.
JP-A-8-317782 JP 2004-256437 A JP 2002-161075 A JP 2002-161004 A

  Accordingly, an object of the present invention is to solve the above-mentioned problems, and to provide a bactericide and an antibacterial agent that are extremely safe and have little environmental burden.

As a result of diligent studies to achieve the above object, the present inventors have found that 2H-pyran-2-one-4,6-dicarboxylic acid (hereinafter referred to as “PDC”) represented by the following formula (I): ) Has been found to have antibacterial and antibacterial effects against gram-negative and gram-positive bacteria, and the present invention has been completed.
That is, the present invention relates to the formula (I):

[Wherein, R ¹ and R ² each independently represent H or CH ₂ — (CH ₂ ) _n —OH (n is an integer of 1 to 4). However, R ¹ and R ² are not H at the same time. ]
The antibacterial agent and antibacterial agent which use the compound represented by these as an active ingredient are provided.

According to the present invention, the compound represented by the formula (I) has excellent antibacterial action and antibacterial action.
Therefore, the compound represented by the formula (I) is industrially useful as a component of antibacterial and antibacterial agents, which are extremely safe because they have a natural product-derived material as a starting material, and have almost no burden on the environment. is there.

The preservative and the antibacterial agent of the present invention include a compound represented by the formula (I) (hereinafter referred to as “compound (I)”). Specifically, the compound (I) includes R ¹ and R ² is the following: R ¹ = H and R ² = CH _2- (CH ₂ ) _n -OH; R ¹ = CH _2- (CH ₂ ) _n -OH and R ² = H; or R ¹ = CH ₂ - _{(CH 2)} n -OH, and _{^{R 2 = CH 2 - (CH}} 2) n -OH ( where, n is an integer from 1 to 4) is a compound represented by the group.

The production method of compound (I) is not particularly limited. For example, starting from vanillin, syringaldehyde, vanillic acid, syringacic acid or protocatechuic acid, PDC fermentation fermentation plasmid pKTVLABC is introduced into Pseudomonas bacteria ( Pseudomonas putida PbY1100). After producing PDC using the method of culturing the transformed cells thus introduced (Japanese Patent Application Laid-Open No. 2005-278549), it can be conveniently carried out by an ester synthesis method by dehydration reaction between carboxylic acid PDC and a diol compound such as ethylene glycol. And can be obtained with high purity.

  The content of the compound (I) in the antibacterial agent and antibacterial agent of the present invention is usually 0.1 to 50% by mass, preferably 0.1 to 10% by mass.

  The antibacterial agent and antibacterial agent of the present invention exhibit excellent antibacterial or antibacterial activity against various bacteria. Examples of such bacteria include Staphylococcus aureus, Bacillus subtilis, coagulase negative staphylococci, Gram-positive bacteria such as streptococci and enterococci; Gram-negative bacteria such as Escherichia coli, Shigella, Salmonella and Plasmodium.

  The antibacterial and antibacterial agents of the present invention contain the compound of formula (I) as an active ingredient, but the compound having a hydroxyalkylene group bonded to a carboxyl group has a very low acidity of the carboxylic acid and is neutral as an aqueous solution. Therefore, there is almost no possibility of metal corrosion.

  The antibacterial agent and antibacterial agent of the present invention can be added to foods and drinks, cosmetics, oral products, pharmaceuticals, quasi drugs, etc. to prevent bacterial growth, and these packaging materials, antibacterial sheets, Applicable to antibacterial processed products and antibacterial sprays.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these Examples at all.

Example 1
<Test substance>
As a test substance, a PDC diester obtained by reacting excess ethylene glycol with PDC and dehydrating and condensing it was used.

<Production example>
Pour ethylene glycol (100 mL, 1.79 mol) into a four-necked flask equipped with a Liebig condenser and a football-type stirrer, raise the temperature to 120 ° C, and add PDC (22.86 g, 0.12 mol) and 10 drops of hydrochloric acid. In addition, it was dissolved. When PDC was completely dissolved, the pressure was gradually reduced to 115 mmHg using an aspirator, and the reaction was continued for 6 hours until no by-product water was produced. After the reaction, the temperature was lowered to room temperature, and further cooled in a freezer to obtain a white solid. The obtained solid was recrystallized with ethanol three times to obtain the target white solid (15.66 g, yield 46.3%).

<Controls and reagents>
Sterile purified water (Japan Pharmacopoeia purified water: Nippon Shinyaku Co., Ltd., high-pressure steam sterilization treatment)
Sterile phosphate buffer (PRo-media MV2-1000, Elmex Corporation)
<Preparation of each 10%, 1.0%, and 0.1% test substances>
10% aqueous solution: 1 g of the test substance was weighed and made up to 10 mL with sterile purified water.
1.0% aqueous solution: A 10% aqueous solution was diluted 10-fold with sterilized purified water.
0.1% aqueous solution: A 10% aqueous solution was diluted 100-fold with sterilized purified water.
<Strain>
Staphylococcus aureus subsp. Aureus (Staphylococcus aureus subspecies aureus) (NBRC 13276)
Escherichia coli (NBRC 3972)
Salmonella Enteritidis (NBRC 3313)
The number in the parenthesis indicates the standard strain number.
<Medium>
Trypke Susoi Agar (SCD medium, manufactured by Biomeryu Japan)
<Sterile petri dish>
Sterilization NE Petri dish (Eiken Equipment Co., Ltd.)

<Preparation of inoculum solution>
The above strain was cultured on an SCD agar medium at 35 ± 2 ° C. for 18 to 24 hours, suspended in sterilized purified water, and adjusted to the turbidity of MacFarland No. 1 as an inoculum. The concentration of the inoculum was measured using an agar medium according to the agar plate pour method (Table 1).

<Test procedure>
3 mL each of 10%, 1.0%, and 0.1% test substances and sterilized purified water (control) were prepared (n = 1). Each test solution was inoculated with 0.05 mL of the above inoculum at room temperature. After inoculating for 15 minutes, 1 hour, 3 hours and 24 hours at room temperature, add 49.5 mL of 49.5 mL of sterile phosphate buffer (Pro-media MV2-1000, Elmex Corp.) to 0.5 mL of the test solution and mix. did. A 10-fold dilution series of each mixture was prepared, the number of viable bacteria was measured, and converted to the number of bacteria in 1 mL of the sample or control. The number of viable bacteria was measured according to the “14th revision Japanese Pharmacopoeia Viable count measurement agar plate pour method”. The results are shown in Table 2.

As is apparent from Table 2, the composition of the present invention containing a diester body exhibited excellent antibacterial and antibacterial effects.
Similar results were obtained even when monoesters or diesters having different R ¹ and R ² were used (data not shown).

Claims (2)

Formula (I):

[Wherein, R ¹ and R ² each independently represent H or CH ₂ — (CH ₂ ) _n —OH (n is an integer of 1 to 4). However, R ¹ and R ² are not H at the same time. ]
An antibacterial agent comprising a compound represented by the formula: Formula (I):

[Wherein, R ¹ and R ² each independently represent H or CH ₂ — (CH ₂ ) _n —OH (n is an integer of 1 to 4). However, R ¹ and R ² are not H at the same time. ]
The antibacterial agent which uses the compound represented by this as an active ingredient.