JPS6045176B2 - New oxybenzoic acid ester and antiseptic agent for industrial products containing it as an active ingredient - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides novel oxybenzoic acid esters having excellent bacteriostatic and bactericidal effects represented by the general formula (1) (wherein n represents an integer of 1 or 2) and This invention relates to an antiseptic agent for industrial products containing benzoic acid ester as an active ingredient.

Currently, alkyl esters of roseoxybenzoic acid are used in bacteria,
It is widely used as a preservative and anti-bacterial agent for pharmaceuticals, quasi-drugs, cosmetics, and other industrial products because it has strong growth-inhibiting or bactericidal properties against fungi, yeast, and molds, and low toxicity and irritation to the human body. It is used.

In particular, lower alkyl esters of roseoxybenzoic acid, such as ethyl, propyl, butyl, isopropyl, and isobutyl esters, are permitted to be used as food additives due to their high safety as preservatives, and are actually used in soy sauce, Used as a preservative in foods such as sauces. The present inventors synthesized various oxybenzoic acid esters and investigated their biological activities. As a result, the novel oxybenzoic acid esters represented by the above general formula (1) were found to be the above-mentioned conventional commercially available preservatives and anti-bacterial agents. It has a stronger bactericidal effect against microorganisms, especially gram-positive bacteria and gram-negative bacteria, than the alkyl ester of roseoxybenzoic acid used as a hydroxybenzoic acid, and is non-toxic to the human body or has very low toxicity and is irritating to the skin. They discovered that there is no such thing and completed the present invention.

Representative examples of the oxybenzoic acid ester represented by the general formula (1) in the present invention are shown below.

Compound number Structural formula 2-ethylhexyl 3,4-dioxybenzoate The oxybenzoic acid ester represented by the general formula (1) of the present invention is, for example, the general formula (■) (where M represents an alkali metal and n is It is obtained by reacting an alkali metal salt of oxybenzoic acid represented by the general formula (having the same meaning as in (1)) with 1-halogeno-2-ethylhexane.

This reaction is preferably carried out in a solvent such as benzene, acetone, dimethylformamide, etc. by heating at a temperature ranging from about 50° C. to the boiling point of the solvent used. General formula (■)
Examples of alkali metal salts of oxybenzoic acid represented by oxybenzoic acid include hydroxybenzoic acid, metaoxybenzoic acid, orthoxybenzoic acid, 2,4-dioxybenzoic acid, 3,4-dioxybenzoic acid, and 2,5-dioxybenzoic acid. Examples include potassium salts and sodium salts of benzoic acid, and considering the strength of the antibacterial activity of the target oxybenzoic acid ester represented by the general formula (1), hydroxybenzoic acid, or 3,4- Alkali metal dioxybenzoic acid is preferred. Further, as the 1-halogeno-2-hexane, 1-chloro-2-ethylhexane, 1-bromo-2-ethylhexane, etc. can be used. The oxybenzoic acid ester represented by the general formula (1) is
One type or a mixture of two or more of these esters can be used as is as a preservative and anti-biking agent for industrial products, and one or more of the hydroxybenzoic acid esters can be used in combination with various dilution aids, such as solvents. It can also be used as a preservative and binder for industrial products by blending it with a surfactant or the like to formulate it in the form of an emulsion, a wettable powder, or the like. When using the antiseptic agent for industrial products containing the oxybenzoic acid ester represented by the general formula (1) of the present invention as an active ingredient, it is recommended to use the antiseptic agent for industrial products such as pharmaceuticals, pharmaceuticals, etc. that should be prevented from being damaged by the action of microorganisms. The preservative is applied to industrial products such as external products, cosmetics, textile and paper products, leather products, wood products, paints, plastic materials, metals, electronic equipment, and optical equipment, depending on the shape of these products. It can be mixed, applied or sprayed.

In addition, when mixed with cosmetics such as medicated soaps, cosmetic soaps, lotions, lotions, and creams, they may cause skin disinfection or impetigo, hair follicles caused by shaving, folliculitis, acne, skin irritation, and eczema. It is effective in preventing skin diseases.
Furthermore, by mixing the preservative and anti-bacterial agent of the present invention with a cleaning agent, the cleaning effect thereof can be improved. The amount of the preservative and antibacterial agent of the present invention to be used is usually 50 to 50% in terms of the amount of the active ingredient of the oxybenzoic acid ester represented by the general formula (1) to be included in, for example, quasi-drugs, cosmetics, or paints.
Approximately 2000 ppm is suitable. Below, the general formula (1
) Synthesis examples of the oxybenzoic acid esters shown in the following are shown, as well as test examples and effect examples to clarify the effects of the oxybenzoic acid esters on microorganisms.

Synthesis Example Potassium Oxybenzoate 14.1f! ,
60 mL of dimethylformamide and 0.85 f of trimethylstearylammonium chloride were placed in a 200 ml three-necked flask, and the temperature was raised to 80°C using an oil bath while stirring.
The temperature was maintained at 0-90°C.

After making a homogeneous solution, 21.16q of 1-bromo-2-ethylhexane was added dropwise by appropriate dropwise loading. As the reaction proceeded, the production of potassium bromide was observed. 5
After reacting for an hour, dimethylformamide was distilled off from the reaction solution under reduced pressure, and then 60 mt of benzene was added.

Insoluble materials were separated from the benzene, and the oral fluid was neutralized with a 10% aqueous sodium bicarbonate solution and extracted three times with water. The benzene layer was collected and concentrated using an evaporator to obtain 9.0 g of a yellow crude product. Next, this crude product was recrystallized using benzene to obtain pale yellow candy-like crystals of 2-ethylhexyl roseoxybenzoate 16y. NMR spectral data of this product is shown below. NMR spectrum (10QMHz) δ♀deS; 0.82(t)6H1
1.1-1.8 (m) 9H; 4.08 (d)? ;6.7
8(d), 7.74(d) 4H Test Example 1 The MIC (minimum inhibitory concentration) for various microorganisms was
Shown in the table.

Test method: Dilute the test solution with a concentration of 10ml91ml in 10 steps, put 1nt of each concentration into a Petri dish, add 9ml of nutrient agar medium, mix well before solidifying, and prepare a flat plate.

On the other hand, one platinum loopful of bacteria was transplanted into a test tube containing 107 nt of peptone water, and heated at 37°C for 2 gi! Perform static culture for f. This culture solution was applied to a platinum loop and the above plate, and heated at 37°C.
After culturing for a certain amount of time, determine the minimum concentration that inhibits the growth of the applied bacteria. The bacterial strains used in the test are shown below. Strain No. l Staphylococcus aureus FD
A2O9PNO. 2 Staphylococcus aureus
Newrrlan NO. 3 Bacillus Subtilis IAMlO69NO. 4
Bacillus ●Cereus NO. 5 Sarcina Lutea IFO3
232NO. 6 Corynebacterium equi IAMlO38 NO. 7 Mycobacterium avium IFO3l54N
O. 8 Mycobacterium frei 1F03158N0.
9 No Chaldea Asteroides IFO342
4 NO NO. lO Aerobacter ●Aerogenes C1
12N0.11 Ethelicia CoIJIAMl239
NO. l2 Serratia Marusetsu sense IFO3736N
O. l3 Proteus vulgaris IFO3O45NO.
l4 Salmonella Teifu Murium IF'012
529 N0.15 Pseudomonas aeruginosa AK
U823 The numbers in the table indicate the concentration of the compound that inhibits bacterial growth.
Indicated by 1.

Test Example 2 The phenol coefficient (bactericidal effect) against various microorganisms was
Shown in the table.

Test method: Staphylococcus aureus FDA2O9
P. is cultured with shaking for two hours using a nutrient liquid medium.

2. Dilute the test drug solution appropriately with sterile distilled water, add 1 ml of the above bacterial solution to 10 ml of the solution, and keep at 20°C.
After 5 minutes, 10 minutes, and 1 time after washing, about 1 platinum loopful was taken and mixed into a new nutrient liquid medium. Immediately, a portion of this was applied to a nutrient agar medium, cultured on a 3rc12 plate, and then the viability of the bacteria was determined. The phenol coefficient was defined as the ratio of the maximum dilution of the test drug solution at which bacteria were not killed within 5 minutes of action and killed after one application to the maximum dilution of phenol that yielded the same result.
Effect Example 1 A base was prepared by adding 10 g of glycerin to a white ointment consisting of 10 f of purified lanolin, 10 y of salami beeswax, and 80 g of white petrolatum.

Compound (1) was added to base 12.5f at 4γ1y120γ, respectively.
1y1100γIy added and non-additive were prepared and each was incubated at 37C using broth liquid medium.
1 ml of culture solution of Staphylococcus aureus FDA2O9P bacteria cultured with shaking for 2 hours (number of bacteria approximately 1 CP to 10
After seeding (10 seeds/ml) and stirring thoroughly, the seeds were placed in a glass container filled with water and cultured at 27°C. After culturing for 2 days, 3 days, and 4 days, one platinum loopful of each base was taken, spread on a bouillon plate, and cultured for 2 days.
The number of growing bacteria (number of colonies) was investigated, and the mortality rate was calculated.

Note that the mortality rate (%) = 100 - (number of viable bacteria/number of viable bacteria without additives) x 100. The results are shown in Table 3. Effect Example 2 Stearic acid 12%, liquid paraffin 6.0%, white beeswax 4.0%, surfactant (Span2O) 4.0
%, glycerin 5.0%, purified lanolin 1.0%, triethanolamine 0.3%, and distilled water 67.7%.

Claims (1)

[Claims] 1. An oxybenzoic acid ester represented by the general formula ▲There are numerical formulas, chemical formulas, tables, etc.▼ (in the formula, n represents an integer of 1 or 2). 2. The oxybenzoic acid ester according to claim 1, which is a compound represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼. 3. A preservative for industrial products containing an oxybenzoic acid ester represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (in the formula, n represents an integer of 1 or 2) as an active ingredient. 4. A preservative for industrial products according to claim 3, wherein the oxybenzoic acid ester is a compound represented by the formula ▲ Numerical formula, chemical formula, table, etc. ▼.