JPS6045174B2 - Novel hydroxybenzoic 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 hydroxybenzoic acid esters having excellent bacteriostatic and bactericidal effects represented by the general formula (wherein n represents an integer of 1 or 2) and the hydroxybenzoic acid esters. The present invention relates to a preservative and binder for industrial products containing as an active ingredient.

Currently, alkyl esters of rose hydroxybenzoic acid have strong growth-inhibiting or sterilizing properties against bacteria, fungi, yeasts, and molds, and are low in toxicity and irritation to the human body, so they are used in pharmaceuticals, quasi-drugs, cosmetics, and other products. It is widely used as a preservative for industrial products.

In particular lower alkyl esters of rose hydroxybenzoic acid,
For example, 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 as preservatives in foods such as soy sauce and sauces. has been done. The present inventors synthesized various hydroxybenzoic acid esters and investigated their physiological activities. As a result, the novel hydroxybenzoic acid esters represented by the above general formula (1) were found to be useful as conventional commercially available preservatives and anti-bacterial agents. It has a more pronounced bacteriostatic and bactericidal effect against microorganisms, especially gram-positive bacteria and gram-negative bacteria, than the alkyl ester of rose hydroxybenzoic acid used, and is also non-toxic or extremely low-toxic to the human body. It was discovered that there is no skin irritation, leading to the completion of the present invention.

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

Compound number Structural formula General formula (1) of the present invention
The hydroxybenzoic acid ester represented by, for example, the general formula "(wherein M represents an alkali metal, and n represents the general formula (
It is obtained by reacting an alkali metal salt of hydroxybenzoic acid represented by 1) (having the same meaning as 1) with 1-halogeno-2,7-octadiene.

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. Examples of the alkali metal salts of hydroxybenzoic acid represented by the general formula (■) include potassium salts and sodium salts of hydroxybenzoic acid such as hydroxybenzoic acid and 3,4-dihydroxybenzoic acid; As the 2,7-octadiene, 1-chloro-2,7-octadiene, 1-bromo-2,7-octadiene, etc. can be used. The hydroxybenzoic acid ester represented by the general formula (1) can be used as it is as a preservative and a binder for industrial products as one type or a mixture of two or more thereof.
A type or two or more types can be mixed with various appropriate dilution aids, such as solvents and surfactants, to create formulations in the form of emulsions, wettable powders, etc., and used as preservatives for industrial products. I'll come.

When using the preservative and binder for industrial products containing the hydroxybenzoic acid ester represented by the general formula (1) of the present invention as an active ingredient, the preservative and binder may be used as a pharmaceutical, quasi-drug, or
Cosmetics, textiles, paper products, leather products, wood products, paints,
It may be mixed, applied, or sprayed onto industrial products such as plastic materials, metals, electronic devices, and optical machines, depending on the shape of these products.

In particular, when mixed with cosmetics such as medicated soaps, cosmetic soaps, lotions, lotions, and creams, it 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% in terms of the amount of the active ingredient of the hydroxybenzoic acid ester represented by the general formula (1) contained in, for example, quasi-drugs, cosmetics, or paints.
Approximately 0 to 2000 ppm is appropriate. Examples of the synthesis of the hydroxybenzoic acid ester represented by the general formula (1) are shown below, as well as test examples and effect examples for clarifying the effects of the hydroxybenzoic acid ester on microorganisms.

Synthesis Example 3.12q1 of potassium hydroxybenzoate, 30ml of dimethylformamide, and 0.25y of trimethylstearylammonium chloride were placed in a 100Tf 1.1 volume three-necked flask, and the temperature was raised to 80~80°C using an oil bath while stirring.
It was maintained at 90°C.

After making a homogeneous solution, 1-bromo-2 is added by dropwise loading.
- 7-octadiene 5y was added dropwise. As the reaction proceeded, the production of potassium bromide was observed. After reacting for 5 hours, dimethylformamide was distilled off from the reaction solution under reduced pressure, and then 30 mL of benzene was added.

Materials insoluble in benzene were separated, 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 2.5y of a yellow oily crude product. Next, this crude product was separated and purified by silica gel column chromatography (Wako Gel C-2001 benzene developing solution), and a pale yellow candy-like rose hydroxybenzoic acid 2,7-octadienyl ester 1.
I got 6y. The nuclear magnetic resonance spectrum data of this product is shown below. NMR spectrum (100MHz) δ弗? 13:1.2-1.6(m)2H;1.8-2.2(
m) 4H; 4.5-5.0 (m) 4H; 5.3-5.9
(m) 3H; 6.70 (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 1ml 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, about 1 platinum loop of bacteria was transplanted into a test tube containing 10 mL of peptone water, and statically cultured at 37° C. for 241 hours.
Apply one platinum loopful of this culture solution to a previously prepared flat plate, and
rC. ．． Incubate for hours. Then, determine the minimum concentration that inhibits the growth of the applied bacteria. The bacterial strains used in the test are shown below. The numbers in the table indicate the concentration of the compound that inhibits bacterial growth in Rlmt.

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

Test method: Staphylococcus aureus FDA2O9
Culture P using a nutrient liquid medium with shaking between two plates.

On the other hand, the test drug solution was appropriately diluted with sterile distilled water, 10 ml of the solution was prepared in a large test tube, 1 ml of the above bacterial solution was added thereto, and the mixture was heated at 20°C for 2.5 minutes, 5 minutes, and 10 minutes. minute, 1
After 5 minutes of contact, about 1 platinum loop of the mixture was mixed with a new nutrient liquid medium, and this portion was immediately applied to a nutrient agar medium and cultured at 37°C for 2 cells to kill the bacteria. I judged it. 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. 5 Effect Example 1 A base was prepared by adding 10 f of glycerin to a white ointment consisting of 10 y of purified lanolin, 10 y of white beeswax, and 80 f of white petrolatum.

Compound (1) was added to base 12.5f at 2γIyllOγ1f.
Prepare one with 150γ1y added, one with 150γ1y added, and one without.
1 ml of culture solution of Staphylococcus aureus FDA2O9P bacteria cultured with shaking for 2 hours (number of bacteria approximately 1 CP to 10
The cells were inoculated with 10 cells/ml), stirred well, and then placed in a glass container 7 that had been drained with water, and cultured at 27°C. 3
After culturing for 24 hours and 24 hours, one platinum loopful of each base was applied to a bouillon plate and cultured for 2 hours.The number of growing bacteria (number of colonies) was determined 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%, refined lanolin 1.0%, triethanolamine 0.3%, and distilled water 67.7%.

Compound (1) was added to base 12.5y at 0.01% and 0.01%, respectively.
Staphylococcus aureus FDA2O9P prepared with 2% additive and without additive and cultured with bouillon liquid medium at 37C for 2 hours with shaking.
1ml of bacterial culture solution (number of bacteria approximately 1σ to 1010/TILL
) was inoculated, stirred thoroughly, and then placed in a glass container filled with water and cultured in a constant temperature bath at 27°C. After culturing for a certain period of time, take one platinum loopful of each base, spread it on a bouillon plate and incubate for two hours, and then calculate the number of growing bacteria (
The number of colonies) was investigated, and the mortality rate was calculated. The results are shown in Table 4. Effect Example 3 Distilled water was added to 10TrLt of squeezed orange juice passed through gauze and 10y of sucrose to make orange juice (PH=4
．． 2) 100ml was prepared and heat treated at 80'C.

Add 10% of compound (1) to 25ml of prepared tangerine juice.
Penicillium with and without additives were prepared in sterilized 100 ml Erlenmeyer flasks so that γImlllOOylmLl, respectively, and cultured for 1 hour at 2rC using a ginger slant medium.
After adding 1.5 ml of a bacterial suspension of Metatum IFO464O bacteria and stirring well, culture was performed in a constant temperature bath at 27°C, and the growth rate of the bacteria was observed. The results are shown in Table 5. However, − indicates that no growth of the fungus is observed.

+ indicates slight bacterial growth.

Considerable bacterial growth is observed in the area.

Significant bacterial growth is observed on the citrus fruits.

Claims (1)

[Scope of Claims] 1. A hydroxybenzoic acid ester represented by the general formula (numerical formula, chemical formula, table, etc.) (in the formula, n represents an integer of 1 or 2). 2. The hydroxybenzoic 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 a hydroxybenzoic 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 and antibacterial agent for industrial products according to claim 3, which is a compound represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼.