JP2883758B2 - UV-induced mutation inhibitor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an ultraviolet ray-induced mutation inhibitor which has an excellent effect in preventing skin cancer caused by ultraviolet rays.

[0002]

BACKGROUND OF THE INVENTION There are many mutagens in our daily environment, many of which are carcinogens and threaten our health. Plant components such as flavonoids and flocoumarin are known as mutagenic substances that occur in nature, and the pyrolysates of tryptophan during burning of grilled fish and aflatoxins, which are typical mold venoms, are also strongly mutagenic. Has been found to have

[0003] Further, efforts are being made to elucidate the mechanism of mutagenesis of these mutagenic substances in living organisms, search for substances for suppressing mutagenesis, and elucidate the mechanism.

[0004] For example, it has been discovered that enzymes contained in vegetables and the like degrade mutagen, and that dietary fiber has the effect of adsorbing mutagen to inactivate mutagenicity. It has been found that the action inactivates the production of a nitroso compound, and the mechanism of inactivating a mutagenic substance has been gradually elucidated.

In recent years, the destruction of the ozone layer due to the emission of a large amount of chlorofluorocarbon gas and the accompanying effect of an increase in the amount of ultraviolet irradiation on the ground have been taken up as factors such as an increase in skin cancer and other diseases. In particular, short-wavelength ultraviolet light with a main peak at 254 nm, which has been largely absorbed by the ozone layer, has a strong harmful effect on living organisms including humans and is a wavelength region that is mutagenic. The most important thing to note is UV.

[0006] Recently, effective substances have been found which directly suppress the mutation in cells induced by irradiation with this short-wavelength ultraviolet ray. The discovery of an effective substance that directly suppresses mutations in cells and the elucidation of the mechanism of suppression of the mutagenesis are considered to be extremely useful for prevention and treatment of skin cancer and the like caused by ultraviolet rays.

Heretofore, as a substance that directly suppresses mutations in cells induced by ultraviolet light, derivatives of tannic acid (mutation research (Mut.
s), 173, 239-244, 1986), lactone compounds (Agricultural and Biological
Chemistry (Agric. Biol. Chem)., Volume 50, Issue 1, 24
3 to 245, 1986), derivatives of furanone compounds (
Agricultural and biological chemistry (Agric. Biol. Chem.), Volume 50, Issue 3, page 625-
631 (1986), and structural analogs of vanillin (Chemistry and Biology, 26, 3, 161 to 172, 1988).

However, these chemicals are not always satisfactory in terms of the effect of inhibiting UV-induced mutation and the safety thereof. Therefore, a novel inhibitor excellent in the above effects and excellent in safety is desired. I was

Accordingly, an object of the present invention is to provide an ultraviolet-induced mutation inhibitor excellent in the effect of inhibiting ultraviolet-induced mutation, which is expected to have an excellent effect of preventing skin carcinogenesis due to ultraviolet light, and which is excellent in skin safety. Is to provide.

[0010]

Means for Solving the Problems The present inventors have conducted intensive studies on inhibitors against UV-induced mutation, and as a result, disclosed in
As disclosed in Japanese Unexamined Patent Publication No. -294396, the present inventors have found that dehydrodioigenol, which is safe in skin irritation and sensitization, exhibits an excellent inhibitory effect on ultraviolet ray-induced mutation, thereby completing the present invention. .

That is, the present invention provides the following structural formula

Embedded image Is a UV-induced mutation inhibitor containing dehydrodieugenol as an active ingredient.

Hereinafter, the configuration of the present invention will be described in detail.

The dehydrodioigenol of the present invention can be produced, for example, by the method of Fujita et al. (Journal of the Chemical Society of Japan., Vol. 87, No. 9, p. 1002,
1966).

That is, a small amount of iron (II) sulfate is added to a mixture of eugenol and pyridine, and the mixture is stirred at 60-70 ° C. for 8 hours while dropping hydrogen peroxide. Further, hydrogen peroxide is similarly added and the mixture is stirred at 60-70 ° C for 8 hours. This operation is repeated 5 times, and after the reaction, the reaction mixture is extracted with ether, washed with 5% sulfuric acid, and the ether is distilled off. Then, the residue in the flask is recrystallized from ethanol to obtain dehydrodieugenol.

The amount of the dehydrodieugenol is as follows:
It is 0.01 to 5.0% by weight, preferably 0.05 to 1.0% by weight, based on the total amount of the external preparation for skin.
If the content is less than 0.01% by weight, the desired effect of the present invention cannot be sufficiently obtained, and if it exceeds 5.0% by weight, the effect corresponding to the increase cannot be improved.

The ultraviolet-induced mutagenesis inhibitor of the present invention can be used as an external preparation for skin, and its dosage form is not particularly limited. For example, creams, emulsions, packs, lotions, powders, etc. , Oils, ointments and the like,
It can be obtained by being blended with a base composed of raw materials such as a commonly used cosmetic.

[0017]

The present invention will be described below in detail with reference to examples.

Example 1 Method for producing dehydrodieugenol A small amount of iron (II) sulfate was added to a mixture of 20 g of eugenol and 20 g of pyridine, and the mixture was stirred at 60-70 ° C. for 8 hours while dropping 20 g of 30% hydrogen peroxide. Further, hydrogen peroxide is similarly added and the mixture is stirred at 60-70 ° C for 8 hours. Perform this operation 5 times, and add a total of 100 g of 30% hydrogen peroxide. After the reaction, the reaction mixture is extracted with ether, washed with 5% sulfuric acid, and the ether is distilled off. The residue in the flask was recrystallized from ethanol to obtain 35.3 g (yield 90%) of dehydrodieugenol as colorless plate crystals having an mp of 105 ° C.

Mutation Inhibitory Effect The inhibitory effect of dehydrodioigenol on UV-induced mutations was determined by Salmonella typhimurium TA102.
Ames method using strain (hereinafter abbreviated as TA102) (Ames et al., Mutation Research., Ames. BNe)
tal., MutationRes., vol. 31, p. 347, 1975).

(1) Preparation of measurement sample The dehydrodieugenol obtained by the above-mentioned production method was adjusted to a concentration of 4 μg / ml with dimethylsulfoxide (hereinafter abbreviated as DMSO), and further diluted in 5 steps for measurement. The sample was prepared. Germicidal lamps (SANKYO DENKI. GERMICIDAL LAMP) 15W were used as mutagen, 254nm short wavelength ultraviolet light, 7.
3 and J / m ² illumination.

(2) Mutagenicity test method For each 100 μl of each sample solution, 500 μl of a 100 mM sodium phosphate buffer solution (pH 7.4) and a preculture of TA102
After 100 μl of the mixture was mixed and irradiated with ultraviolet rays, 2 ml of soft agar was added, and the mixture was solidified on a minimal glucose agar plate medium and cultured at 37 ° C. for 2 days. After the culture, the number of revertant colonies on the plate was counted.

The evaluation of the mutagenic effect was performed by counting the number of colonies per plate (A), the number of colonies containing only the mutagen (B), and the number of spontaneously returning colonies containing only DMSO (C) ) Was calculated by calculating the mutation rate according to the following equation.

## EQU1 ## Mutation rate (%) = [(A−C) / (B−C)] × 100

(3) Results Table 1 shows the mutagenicity of ultraviolet rays.

[Table 1]

Next, the effect of dehydrodioigenol on the suppression of ultraviolet light-induced mutagenesis against short-wavelength ultraviolet light (7.5 J / m ² ) was examined. As shown in Table 2, the mutation rate of the mutagen alone was 100%. %, A decrease in mutation rate was observed with an increase in the amount of sample added. Therefore, it was confirmed that dehydrodioigenol had an excellent mutation suppressing effect on ultraviolet rays.

[0025]

[Table 2]

[0026]

As described above, the present invention is an extremely useful ultraviolet ray-induced mutation inhibitor which is safe for the skin and has a remarkable inhibitory effect on ultraviolet ray-induced mutation.

Claims (1)

(57) [Claims] 1. The following structural formula: An ultraviolet-induced mutation inhibitor comprising as an active ingredient dehydrodieugenol.