JP2552297B2 - Beautiful skin cosmetics - Google Patents

Description

TECHNICAL FIELD The present invention relates to a cosmetic containing 3,5-dimethoxy-4-hydroxycinnamic acid and / or a derivative thereof.

More specifically, the present invention, by the action of 3,5-dimethoxy-4-hydroxycinnamic acid or a derivative thereof, prevents sunburn due to ultraviolet rays, and is provided with a whitening effect as well as a stain / freckle reducing effect due to thyrodinase activity inhibition, Further, the present invention is intended to provide a novel cosmetic for beautiful skin that can suppress the acceleration of skin aging due to light.

(Problems to be Solved by Prior Art and Invention) Generally, when the skin is exposed to excessive ultraviolet rays outdoors, sunburn occurs in several hours after exposure to sunlight,
When it gets worse, it causes blisters. Furthermore, pigmentation subsequently occurs. Thus, excessive UV exposure is extremely harmful from both an aesthetic perspective and the health of the skin.

So far, the main cause of the above-mentioned symptoms is 290 to 320 nm of medium-wavelength ultraviolet rays (hereinafter UV-
It is called B. ), Especially the most involved in "erythema induction" 305-3
Ultraviolet rays in the vicinity of 10 nm has been emphasized, and discussions have been made on how to prevent this.

However, recently, the harmful effect of long-wavelength ultraviolet rays of 320 to 400 nm (hereinafter referred to as UV-A) is becoming clear. For example, if UV-A is irradiated before and after UV-B irradiation, UV-
Since the erythema-inducing ability of B is promoted and UV-A reaches the inside of the dermis, it is known that skin aging is caused by the long-term effects on the intradermal components (collagen, glycosaminoglycan, etc.). Came to be.

Many ultraviolet absorbers have been developed in order to prevent the ultraviolet rays, but in reality, few of them have the effects and safety as well as the stability and solubility as a cosmetic raw material. That is, the ultraviolet absorbers that have been used before in Japan are roughly classified into benzophenone type, urocanic acid type, p-aminobenzoic acid type, cinnamic acid type, and others (salicylic acid type, benzotriazole type, etc.). However, for example, the benzophenone series is 280 to 290 nm and 320 to 3
It has an absorption maximum around 30 nm and is one of the widely used raw materials, but on the other hand, it has the property of relatively low absorption around 305 to 310 nm which is most involved in erythema induction. Also, urocanic acid type is a biological component and is highly safe,
Since the absorption maximum is around 280 to 290 nm, the practical effect is low particularly for UV-A. It is said that p-aminobenzoic acid type and cinnamic acid type have a maximum absorption around 300 to 310 nm and a high absorption effect, but have a safety problem such as contact photosensitivity. Further, the benzotriazole type has a drawback that it is not allowed to be incorporated into cosmetics from the viewpoint of safety, and the salicylic acid type has a weak absorption effect, and it is difficult to maintain the function as a sunscreen unless a large amount is incorporated.

In Japan, since the safety of ultraviolet absorbers is emphasized, the actual amount of the ultraviolet absorbers used is regulated to 4 to 5% or less.

Therefore, for high SPF products desired by consumers, it is often the case that inorganic powder such as titanium oxide that physically reflects and scatters ultraviolet rays is used, but in this case the formulation that can be blended is limited, In addition, it may be unsuitable for lotion type or oil type products because the feeling of use during application may deteriorate.

(Means for Solving Problems) In view of the above-mentioned conventional problems, the present inventors have made various searches in order to find a material that is truly safe and excellent in effect, and has both safety and solubility as a cosmetic raw material. As a result of repeated experimental research, a 3,5-dimethoxy 4-hydroxycinnamic acid-based compound, which had never been used practically in cosmetics and was not known for its effect on the skin, was found to be 290 According to the present invention, it has been found that it has a large UV absorption effect in the vicinity of ~ 330 nm and is optimal as a UV absorption agent for cosmetics, and that it has a large thyrodinase activity inhibitory effect in the skin and is excellent in whitening effect. Was completed.

That is, the present invention, as an active ingredient, the general formula (In the formula, R represents hydrogen or a linear, branched, cyclic, or polycyclic alkyl group, alkenyl group, aryl group, and alkali metal, alkaline earth metal, and fourth chain amine.) 3 The present invention relates to a cosmetic for beautiful skin, comprising 5,5-dimethoxy-4-hydroxycinnamic acid and / or a derivative thereof as an active ingredient.

 The present invention will be described in detail below.

The 3,5-dimethoxy-4-hydroxycinnamic acid used in the cosmetic for beautiful skin of the present invention has the general formula (I) (R
Is a substance represented by hydrogen).

Although 3,5-dimethoxy-4-hydroxycinnamic acid has never been practically used in cosmetics until now, as shown in the ultraviolet absorption spectrum (see FIG. 1) described later, it has a wavelength of about 323 nm (ethanol Has a maximum absorption in (middle) and shows an absorption pattern similar to that of benzophenone-based UV absorbers, and there is almost no decrease in absorption capacity in the "erythema-inducing" region (305 to 310 nm) like benzophenone-based UV absorbers. From the above, it was revealed from the experiments by the present inventor that the erythema-suppressing effect and the increase in the number of melanocytes when irradiated with ultraviolet rays on the skin are excellent.

Similarly, according to the inventors' experiments, 3,5-dimethoxy-
It was also clarified that 4-hydroxycinnamic acid has an activity of inhibiting thyrodinase activity, and it was also demonstrated that it is useful for a whitening effect and reduction of spots and freckles.

3,5-Dimethoxy-4-hydroxycinnamic acid is generally a pale yellow to white needle-like or powdery crystal, easy to handle, has no odor, and is hardly soluble in cold water,
Since it is slightly soluble in vegetable oils such as olive oil and soybean oil, esters, etc., but soluble in alcohol and polyhydric alcohol, it can be applied to a wide range of dosage forms even when used as a cosmetic ingredient. On the other hand, in the skin cosmetic of the present invention, 3,
5-Dimethoxy-4-hydroxycinnamic acid may be used as its salt. When used as a salt, the solubility in water is increased, which is particularly preferable for use in lotion and the like. When 3,5-dimethoxy-4-hydroxycinnamic acid is used as a salt, the basic substance for forming the salt includes lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide,
Inorganic bases such as ammonium hydroxide, basic amino acids such as arginine, lysine, histidine and ornithine, and organic bases such as monoethanolamine, diethanolamine and triethanolamine are used. The above-mentioned salt may be prepared in advance and then added, or the salt-forming components may be added separately and reacted in the formulation system to form a salt.

Furthermore, 3,5-dimethoxy-4-hydroxycinnamic acid can also be used as its ester. By using it as an ester, the solubility in oily components is improved, and it becomes suitable for use in cosmetic oils and the like. The method itself for esterifying 3,5-dimethoxy-4-hydroxycinnamic acid can be produced by a known method, for example, an acid halide method, an acid anhydride method, a direct method, a DCC method or the like. The properties of the 3,5-dimethoxy-4-hydroxycinnamic acid ester derivative widely change from crystalline to viscous oily to oily depending on the type of alcohol used for esterification. The ultraviolet absorption characteristics of these 3,5-dimethoxy-4-hydroxycinnamic acid ester derivatives are generally 3 to 4 nm longer than that of 3,5-dimethoxy-4-hydroxycinnamic acid. The absorption maximum shifts (red shift).

Specific examples of the 3,5-dimethoxy-4-hydroxycinnamic acid ester derivative include ethyl 3,5-dimethoxy-4-hydroxycinnamic acid and 2-ethylhexyl 3,5-dimethoxy-4-hydroxycinnamic acid. 3,5-dimethoxy-4-hydroxycinnamic acid allyl, 3,5-dimethoxy-
4-Hydroxycinnamate, 3,5-dimethoxy-4
-Oleyl hydroxycinnamate, 3,5-dimethoxy-4
-Phenyl hydroxycinnamate, 3,5-dimethoxy-4
-Hydroxycinnamate, 3,5-dimethoxy-4
-Hydroxycinnamate, 3,5-dimethoxy-4
Examples include ester compounds of 3,5-dimethoxy-4-hydroxycinnamic acid such as cholesteryl hydroxycinnamate and linear, branched, cyclic, polycyclic alkyl, alkenyl, and aryl alcohols.

In the cosmetic for beautiful skin of the present invention, any one kind or two or more kinds can be selected and used from the group consisting of 3,5-dimethoxy-4-hydroxycinnamic acid and its derivatives. The blending ratio is selected to be 0.01% by weight or more, and a particularly preferable amount is 0.5% by weight or more based on the whole cosmetic. Even if the amount exceeds 10% by weight, there is almost no change in the effect.
It is not necessary to exceed the weight percentage.

The cosmetic base used in the skin-care cosmetic of the present invention may be any base as long as it is a base normally used in skin-care cosmetics, and is not particularly limited. Specific dosage forms include cream, ointment, emulsion, lotion, oil, pack and the like. For example, as a cream base, beeswax, cetyl alcohol, stearic acid, glycerin, propylene glycol, propylene glycol monostearate, polyoxyethylene cetyl ether, etc., and as a lotion base, oleyl alcohol, ethanol, propylene glycol, glycerin. , Lauryl ether,
Examples thereof include sorbitan monolaurate.

The skin-care cosmetic of the present invention is prepared as a cosmetic in a suitable form such as cream, milky lotion, and lotion by a conventional method by appropriately using these principles. In the cosmetic for beautiful skin of the present invention, 3,5-
UV absorbers other than dimethoxy-4-hydroxycinnamic acid and its derivatives, UV scattering agents typified by particulate titanium oxide, allantoin, various medicinal ingredients such as placenta extract, other thickeners, plasticizers, calamines, pigments, Antioxidants, chelating agents, fragrances and the like can be added.

Next, in order to explain the usefulness of the skin-care cosmetic of the present invention in more detail, the melanin inhibitory action of 3,5-dimethoxy-4-hydroxycinnamic acid inhibits the tyrosinase activity known as its mechanism. The results of experimental examples of the action and the action of suppressing the increase in the number of melanocytes by ultraviolet rays and the action of suppressing the erythema are shown below.

Experimental Example 1. Tyrosinase activity inhibitory effect The tyrosinase activity inhibitory effect of 3,5-dimethoxy-4-hydroxycinnamic acid was examined using an enzyme tyrosinase extracted from Harding-Passay mouse melanoma. The enzyme activity was determined by a photometric method in which the amount of dopachrome produced was measured by the absorbance at an absorption maximum of 475 nm using dopa as a substrate. The results are shown in Table 1 showing the thyrodinase activity inhibition rate after 10 minutes of reaction.

(Sample solution concentration) 5 x 10 ^-3 M, 1 x 10 ^-3 M, 1 x 10 ^-4 M (Reaction solution composition) Enzyme solution 0.2 ml 5 mM Dopa 1.0 0.1 M phosphate buffer (pH 6.8) 1.74 Sample Solution 0.06 (total) 3.0 ml As shown in the results of Table-1, 3,5-dimethoxy 4-
It was revealed that hydroxycinnamic acid has a remarkable thyrodinase activity inhibitory action, and was proved to be useful for the whitening action and the reduction of stains and freckles.

Experimental Example 2. Inhibitory effect on melanocyte proliferation by UV rays A group of 6 C57BL mice was placed in the right auricle as a test solution, that is, propylene glycol: ethanol = 1: 1.
0.1 W / V%, 0.5 W / V% in the vehicle consisting of 3,5
A solution of each of -dimethoxy-4-hydroxycinnamic acid and 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid was applied in an amount of 10 µm, and the same amount of vehicle was applied to the left auricle of the mouse.

Next, using the FL20SE30 lamp as a light source, the auricle was placed directly under the light source, and ultraviolet rays of 33 μw / cm ² were irradiated for 20 seconds (about 0.07 joule). The sample was applied to the auricle of the mouse once a day, and the ultraviolet irradiation was repeated once for three consecutive days after the application. After leaving it for 1 week, collect the left and right auricles,
Subsequently, NaBr treatment was performed to separate the epidermis. The epidermis was stained with Dopa to prepare a tissue sample, and the number of melanocytes was counted under a microscope. The results are shown in Table-2 (3,5-dimethoxy-
4-hydroxycinnamic acid) and Table-3 (2-hydroxy-4-methoxybenzophenone-5-sulfonic acid).

As shown in the comparison of Table-2 and Table-3, 3,5
-Dimethoxy 4-hydroxycinnamic acid is a conventionally used 2-hydroxy-4-methoxybenzophenone-
It has the effect of suppressing the increase in the number of melanocytes due to ultraviolet rays equivalent to or more than 5-sulfonic acid, and especially 0.5W.
It was found that at / V% or more, the increase in the number of melanocytes was completely suppressed.

Experimental Example 3. Inhibitory effect on erythema and edema due to ultraviolet rays A group of 8 guinea pigs was shaved on the back, and a bandage with two small holes (circle of 1.5 cm in diameter) was applied to the shaved part and fixed. 30μ of test solution on one site of guinea pig
30 μl of the vehicle alone (control) was applied to the other site. About 0.8 J / cm ^{2 which} is four times the minimum amount of erythema after 1 hour (using the FL20SE30 lamp as the light source, 300
(irradiation with μW / cm ² for 28 minutes), and allowed to stand for a certain period of time for judgment. The method of judgment was to observe with the naked eye 2, 4, 6, 24, 48, 72 hours after irradiation according to the following judgment criteria.
The test solution was 3 W / V%, 10% in a vehicle made of DMSO.
It was prepared by dissolving 3,5-dimethoxy-4-hydroxycinnamic acid at a ratio of W / V% and 2-hydroxy-4-methoxybenzophenone at a ratio of 10 W / V%, respectively. The obtained results (n = 8 for each test solution) were averaged and the final results are shown in FIG.

(Criteria) Mild erythema 0.5 (±) Erythema 1.0 (+) Erythema and weak swelling 1.5 (+ to ++) Erythema and obvious swelling 2.0 (++) Small blister / blister 2.0 (+++) Fig. 2 As shown in Fig. 3, 3,5-dimethoxy-4-hydroxycinnamic acid was already added to conventional 2-hydroxy-4-methoxybenzophenone (10 W / V at a concentration of 3 W / V%).
%) Has a significant effect of suppressing erythema and swelling caused by ultraviolet rays. As described above in detail, the skin-beautifying cosmetic composition of the present invention containing 3,5-dimethoxy-4-hydroxycinnamic acid and its derivative reduces the whitening effect and stains / freckles, and has various harmful effects based on ultraviolet rays. It is an excellent thing that can prevent.

Examples of the skin-care cosmetic of the present invention are shown below. The mixing ratio is parts by weight.

Example 1. Lotion Propylene glycol 10.0 Ethyl alcohol 20.0 Liquid paraffin 2.0 Polyoxyethylene (30) hydrogenated castor oil 1.0 Sodium 3,5-dimethoxy-4-hydroxycinnamate 8.0 Polyethylene glycol 5.0 Citric acid 0.2 Sodium phosphate 0.3 Allantoin 0.05 EDTA-2Na 0.05 Antioxidant 0.02 Perfume 0.2 Purified water 53.18 Example 2. Cream Solid paraffin 2.0 Stearyl alcohol 4.0 Squalane 2.0 Liquid paraffin 6.0 Glyceryl monostearate 2.5 Polyoxyethylene sorbitan monostearate 2.5 Ethyl alcohol 9.0 Propylene glycol 8.0 3, Ethyl 5-dimethoxy-4-hydroxycinnamate 4.0 2-Hydroxy-4-methoxybenzophenone 3.0 Hydrophobized particulate titanium oxide 5.0 Purified water 52.0 Example 3. Foundation Hydrophobized particulate titanium oxide 7.0 isostearic acid triglyceride 2.0 2-octyldodecyl oleate 8.0 liquid paraffin 3.0 cetyl alcohol 5.0 candelilla wax 2.0 3,5-dimethoxy-4-cetyl hydroxycinnamate 5.0 polyoxyethylene (25) monostearate 2.0 sorbitan monostearate 1.0 Yellow iron oxide 1.3 Rouge 0.8 Polyethylene glycol 4.0 Methylparaben 0.2 Fragrance 0.2 Purified water 58.5 Example 4. Powder talc 80.0 Crystalline cellulose 5.0 Ultramarine blue 1.0 Spherical calcium silicate 3.0 Fine titanium oxide 3.5 3,5-dimethoxy-4-hydroxysilica Cholic acid 3.0 Squalane 4.5

[Brief description of drawings]

FIG. 1 is an ultraviolet absorption spectrum of 3,5-dimethoxy-4-hydroxycinnamic acid (in 0.001% ethanol). FIG. 2 shows the relationship between erythema intensity (n = 8 average value) and time course after UV irradiation on guinea pigs. In the figure, (a) is control and (b) is 10 W / V. %
Of 2-hydroxy-4-methoxybenzophenone solution, (c) is applied with 3 W / V% of 3,5-dimethoxy-4-hydroxycinnamic acid solution, (d) is applied with 10 W / V% of 3,5. -Coated with a dimethoxy-4-hydroxycinnamic acid solution.

Claims (2)

(57) [Claims] 1. A formula (I) based on a cosmetic base. (In the formula, R represents hydrogen or a linear, branched, cyclic, or polycyclic alkyl group, alkenyl group, aryl group, and alkali metal, alkaline earth metal, or quaternary amine.) 3 A cosmetic for beautiful skin, comprising 5,5-dimethoxy-4-hydroxycinnamic acid and / or a derivative thereof as an active ingredient. 2. The amount of 3,5-dimethoxy-4-hydroxycinnamic acid and / or its derivative compounded in the cosmetic as a whole in an amount of 0.01 to 10% by weight. Beautiful skin cosmetics.