JPS6185307A - Lightening cosmetic - Google Patents

Abstract

PURPOSE:A skin color-lightening cosmetic that is obtained by adding azelaic acid clathrated with urea to a cosmetic, thus causing no inhibition of antityrosinase activity of the acid with improvement in solubility of the acid and its stability in the emulsion. CONSTITUTION:A zelaic acid which has skin color-lightening effect based on its antityrosinase activity is clathrated with urea to increases markedly its solubility without any adverse effect on the antityrosinase activity and prevent the acid from being precipitated by reduction in system viscosity or pH, when it is added to an emulsion cosmetic. The resultant clathrate is added to cosmetic 0.05-15wt% based on the total weight to give the objective cosmetic which solves horny skins as well as impregnates into skins rapidly and develops treating and preventing effects on pigment desposition in skins such as blots or freckles.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a whitening cosmetic containing a urea clathrate of azelaic acid and used for treating dark spots, freckles, etc.

(Conventional technology) Therefore, it is important to prevent or treat pigmentation such as spots and freckles, and to treat skin after sunburn = 1-
, - recovery promotion, etc.

In order to achieve these objectives, many whitening cosmetics have been developed. However, the safety of whitening agents,
There are advantages and disadvantages in solubility 1 and stability, and the reality is that none of them is satisfactory.

By the way, recently, attention has been focused on the physiological activity of straight-chain aliphatic dicarboxylic acids such as azelaic acid. In other words, the painting style patient (
Focusing on the whitening of the affected area of the white catfish, various studies and tests revealed that dicarboxylic acid was detected, and this dicarboxylic acid was found to have anti-tyrosinase activity, which is believed to have the effect of whitening the affected area of the skin. It has been reported (Japanese Unexamined Patent Publication No. 130433/1983). A method has been proposed in which dicarboxylic acid is used to treat hyperpigmented skin such as age spots and freckles.

Straight-chain aliphatic dicarboxylic acids are organic acids that have traditionally been used as raw materials for cosmetics, but they are rarely used in the form of free acids.

For example, when it is blended into emulsified cosmetics, the pH decreases, the fatty acids precipitate, and the viscosity of the system decreases.
This is because the solubility of linear aliphatic dicarboxylic acids is low in other dosage forms as well as leading to separation of two oil-water layers, resulting in phenomena such as crystallization when administered orally.

In the case of compositions for treating age spots, freckles, etc., due to the above-mentioned drawbacks, a method using diesters obtained by esterification with various alcohols has been proposed (Japanese Patent Application Laid-Open No. 58-1993).
-103319).

However, since the diester itself does not have anti-narosinase activity, when applied to the skin, it is hydrolyzed by esterase present in the epidermis and dicarboxylic acid is liberated, which is a non-constant passive effect. This is an invention that was hoped for.

(Problems to be Solved by the Invention) As a result of intensive research in order to solve the problems of the prior art, the present inventors discovered that azelaic acid, which is one of the linear aliphatic dicarboxylic acids, was By inclusion with , the solubility is significantly improved without affecting the anti-tyrosinase activity, and even when incorporated into emulsified cosmetics, the viscosity of the system is not reduced, and the pII is lowered. However, when applied to the skin, azelaic acid rapidly permeates into the skin due to its keratolytic action, causing stains and stains.
The present invention was completed after discovering that it has a remarkable healing effect (whitening effect) on freckles and the like.

The purpose of the present invention is to prevent the appearance of spots and freckles caused by sunburn, and to lighten pigmented skin such as spots, freckles, and dark skin. This can be achieved by a whitening cosmetic containing a compound (hereinafter referred to as azelaic acid-urea clathrate compound).

The azelaic acid-urea clathrate compound used in the present invention is a white powder with a melting point of 90.4 to 104°C, slightly soluble in water,
Easily soluble in alcohol, slightly soluble in ether.

Insoluble in hexane.

The azelaic acid-urea clathrate compound described above can be purified by, for example, mixing a heated aqueous urea solution and a heated azelaic acid methanol solution with stirring, then cooling with water and washing the precipitate with cold methanol. obtained by The molar ratio of urea to 1 mole of azelaic acid used in this reaction is within the range of 1 to 3 moles.

The content of the azelaic acid-urea clathrate compound (Formulation 1) in the whitening cosmetic composition of the present invention varies depending on the form of the cosmetic composition, but overall it is preferably 0.05 to 15% by weight. If it is less than 0.05%, the inhibitory effect on Tyrocina-V activity will be reduced and it will be difficult to obtain a sufficient whitening effect;
If the amount exceeds 5% by weight, the tyrosinase activity inhibiting effect and whitening effect will not be reduced (the texture of Shiyosaki may tend to be bad, or it may be difficult to maintain each form stably).

The whitening cosmetic of the present invention is in the form of a milky lotion.

Examples include cream, aqueous transparent liquid, and powder.

Other ingredients that may be incorporated into the whitening cosmetic of the present invention include fragrances, anti-scaling agents, excipients, diluents, and adjuvants.

Emulsifiers, oily substances, pigments, skin nutrients, humectants.

Conventional components such as ultraviolet absorbers and pH adjusters can be appropriately blended.

The first feature of the present invention is that since azelaic acid is clathrated with urea, even when the azelaic acid-urea clathrate compound is added to an emulsification system, it does not cause a decrease in pH, precipitation, or a decrease in viscosity. be.

Therefore, by clathrating azelaic acid, which is generally difficult to use in its free form, with urea, it can be advantageously used in cosmetics.

A second feature of the present invention is that the azelaic acid-urea clathrate compound exhibits higher anti-tyrosinase activity than free azelaic acid.

The third feature of the present invention is that the azelaic acid-urea clathrate compound has better keratolytic action, transdermal permeability, and whitening effect than free azelaic acid.

(Example) Hereinafter, the present invention will be explained in detail with reference to Examples.

Note that, although not shown in the examples, % means % in serious condition, and part means severe part.

In addition, the inhibitory effect on tyrosinase activity was confirmed by using commercially available pine mushroom tyrosinase and allowing tyrosinase to act on tyrosine, resulting in 475% of dopa chromium.
The investigation was carried out by a photometry method that measures the absorbance at nm.

2% of the azelaic acid-urea clathrate.

Q, 9 ml of 1%, 0.5% and 0.1% aqueous solution was added with 1 m (Is
v Mr. Kucklhane] 1 tI surgical solution (pI 46.8)
After pre-incubating for 10 minutes in a constant-temperature water bath at 37°C, a tyrosinase aqueous solution (1, OIII/ml) was added.
) was added in an amount of 0.1 n11, stirred well, and reacted at 37°C for 15 minutes, then the absorbance (Dl) was measured at 475 nm. On the other hand, the absorbance (D2
), the azelaic acid-urea clathrate compound as a control, and the absorbance (DB) when tyrosinase was not added were measured, and the tyrosinase activity 1 ull damage rate was calculated from the following formula.

Example 1 A heated aqueous urea solution (80°C) was added to a heated methanol solution (80°C) of azelaic acid, stirred and mixed well, and then cooled on ice to precipitate the urea clathrate of azelaic acid. After separating the P, it was washed with cold methanol, purified and dried, and the results of elemental analysis were analyzed in the first
Shown in the table.

Table 1 The inhibition rate of tyrosinase activity was measured for this clathrate compound, and the results are shown in Table 2. As a control, azelaic acid, urea, and a mixed phase of both were used.

Table 2 As is clear from the results in Table 2, the tyrosinase activity inhibition rate of the azelaic acid-urea clathrate compound is extremely higher than that of azelaic acid.

Example 2 (1) Prescription Ingredient oil phase ■Liquid paraffin 5.0 parts■ Vaseline 2.0■ Beeswax
0.8〃■ Sorbitan monostearate
0.8〃■ Polyoxyethylene cetyl ether (20E, 0.) 1,2
tt aqueous phase ■ Methyl paraben 0.2 ■ Carboxyvinyl polymer (1% aqueous solution) 20.0 // ■ Potassium hydroxide 0.1 ■ Purified water 6B, 2tt [phase] Azelaic acid-urea clathrate compound 2.0 〃■ Propylene glycol 5.0〃■ Fragrance Appropriate amount (2) Preparation method Oil phase components ① to ① were uniformly mixed and dissolved at 80°C. Next, aqueous phase components ① to ①, which had been mixed and dissolved uniformly at 80°C in the same manner, were added to this solution, and after uniformly emulsifying for 15 minutes, [phase] ② was heated to 80°C. The solution and 0 were added and cooled to room temperature to obtain the emulsion of the present invention (formulation (2)).

As control products, a formulation (c) in which azelaic acid was blended in an equal weight percent of azelaic acid in place of the lyazelaic acid-urea clathrate compound in the above formulation, and a formulation in which azelaic acid and urea were blended in an amount of 1 percent by weight (a similar formulation for q) A comparative emulsion was prepared by the method.

(3) Oral stability of the emulsions Table 3 shows the changes in the viscosity of the emulsions of formulations (c), (c), and (Q) over the course of the day.

Table 3 From the results shown in Table 3, the emulsion of formulation (6) containing the azelaic acid-urea clathrate compound shows less decrease in viscosity during long-term oral administration than the emulsion of comparative formulation (c) and (Q). It was stable.

(4) Panel test for whitening effect The whitening effect was investigated by having 20 female subjects suffering from age spots and freckles apply the product once a day in the morning and evening for three months. The results are shown in Table 4. However, prescription 0 means prescription (
C) Naka [Co., Ltd.] It was prepared in the same manner as above, except that the same weight percentage of urea was added instead of the azelaic acid-urea clathrate compound.

Table 4 From the results in Table 4, the whitening effect of the formulation (c) of the present invention is as follows:
Excellent compared to three other (comparative) formulations.

Example 3 (1) Prescription black Ingredients ■ Glycerin 2.0 parts ■ Pyrrolidone carvone (, l l, Q /
/■ Pyridoxine hydrochloride 0.0
57/■ Ethanol 100 〃■
Polyoxyethylene hydrogenated castor oil 04 〃(6
0F, 0. ) ■Purified water 79.55//■ Azelaic acid-urea clathrate compound 2.0〃■ Dipropylene glycol 5.0〃■ Fragrance
Appropriate amount (2) Preparation method Add the above ingredients ■ and ■ to ingredient ■, and add ingredients ■, ■, ■
Dissolve each in the mixture of components (1) and (2). Both liquids and ingredients■
were mixed under stirring to obtain the lotion of the present invention. (Prescription @) In addition, the ingredient ■ in Prescription (C) is added to Azelaic acid (Prescription (G)).
), urea (formulation 0), and a mixture of equal amounts of azelaic acid and urea (formulation @) were used, but comparative lotions were prepared in exactly the same manner.

(3) Panel test for whitening effect 20 test subjects (female) suffering from age spots and freckles applied the product once a day in the morning and evening for 3 months to examine the whitening effect. The results are shown in Table 5.

As is clear from the results shown in Table 5, the formulation of the present invention @
The whitening effect of [Azelaic acid-urea clathrate compound] is more pronounced than that of comparative formulations 0 to 0.

Claims (2)

[Claims] (1) A whitening cosmetic containing a urea clathrate of azelaic acid. (2) The whitening cosmetic according to claim (1), wherein the urea clathrate compound of azelaic acid is contained in an amount of 0.05 to 15% by weight based on the total weight of the prescription ingredients.