JPH0469122B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to cosmetics, and more specifically, compounds represented by the following general formula [], which are blended into a cosmetic base alone or in combination, have a good feeling of use and have a good shelf life. It relates to expensive cosmetics, especially whitening cosmetics. _{NH 2 CH 2 CH 2 _} Hydrogen oxide, ascorbic acid, colloidal sulfur, etc. are commonly used, but these materials cannot be said to be superior in terms of stability, odor, handling, or actual efficacy. It has been an urgent technical challenge in the industry to establish an alternative and superior skin whitening agent. In the cosmetic and dermatological fields, there is a growing interest in preventing skin darkening. The metabolism of tyrosine is as shown in Table 1, and skin darkening is caused by the further oxidation of dopaquinone, which is produced through the involvement of the phenol oxidase enzyme (tyrosinase), which uses tysilone as a substrate and copper ions as a coenzyme. It is caused by polymerization and formation of melanin.

[Table] Therefore, to prevent skin darkening, for example,
Vitamin C derivatives are used in part because they suppress melanin formation by reducing the oxidation process of dopa→dopaquinone→dopachrome. However, its action is not always satisfactorily strong, and the effectiveness of external use is further reduced. On the other hand, a method has been developed to inactivate tyrosinase by binding with Cu ⁺⁺ , prevent oxidation, and suppress melanin formation.
EDTA and the like have been used in some cases, and subsequently, some compounds that have the ability to form chelates with copper have also been developed. However, such compounds have problems in terms of toxicity and irritation, and also have the disadvantage of chelating trace metals that are useful in dermatology, so they are not only useful as skin whitening cosmetics. It has never been used as a cosmetic, nor has it been put to practical use. However, the present inventors have focused again on the mechanism of tyrosine metabolism, which is the main cause of skin darkening, and have developed an excellent active ingredient for cosmetics that is a reducing substance and chelate-forming substance and does not have the above-mentioned drawbacks. For the purpose of development, we conducted various screenings on a large number of organic and inorganic compounds, natural products, synthetic compounds, polymers, and low-molecular compounds. As a result, we discovered several compounds with strong reducing or chelate-forming abilities, and selected compounds that have excellent skin permeability and are particularly suitable for cosmetics, especially skin cosmetics. and,
Furthermore, we conducted extensive research on its safety, formulation compatibility, etc., and as a result, we have completed the present invention. That is, the present invention is a cosmetic for preventing skin darkening (excellent whitening effect) characterized by containing a compound represented by the following general formula []. _{NH 2 CH 2 CH 2 _} It exhibits an excellent melanin formation inhibiting effect and is very effective in preventing skin darkening, and can be advantageously used as a cosmetic, especially a cosmetic with an excellent whitening effect. Regarding the safety of 2-aminoethylsulfinic acid, 2-aminoethylthiosulfonic acid, and 2-aminoethylphosphonic acid, these compounds have been shown to affect the major organs of many mammals, including humans, such as the heart and brain. It is also contained in large amounts in the foods we ingest on a daily basis, and there is no problem with safety, so when it is applied to cosmetics, no toxicity is observed; ,
It is extremely safe, with no side effects such as skin irritation, itching, or rash. Next, a test example will be described to demonstrate that the compound of the present invention exhibits an inhibitory effect on tyrosinase activity. Test example: Add 1 portion of L-tyrosine solution (0.3 mg/ml) to a test tube.
ml, 1 ml of Tris buffer (PH7.2) and 0.9 ml of each solution of 2-aminoethylsulfinic acid, 2-aminoethylthiosulfonic acid, and 2-aminoethylphosphonic acid at each concentration were added, and the mixture was heated at 37°C. After incubating for 10 minutes, 0.1 ml of tyrosinase solution (2000 units/ml) was added and stirred, and immediately the absorbance at 475 nm was measured over time using a spectrophotometer. Also, as a blank test,
A similar operation was performed using water instead of the above test liquid. The results are shown in FIGS. 1, 2, and 3. From this figure, the active ingredient compounds of the present invention, 2-aminoethylsulfinic acid, 2-aminoethylthiosulfonic acid, and 2-aminoethylphosphonic acid, are as follows:
It was found that tyrosinase activity was inhibited at concentrations of 0.5M to 10 ^-1 M. In addition, these inhibitory effects are due to the fact that 2-aminoethylsulfonic acid and 2-aminoethylthiosulfonic acid reduce the oxidation process of dopa→dopaquinone→dopachrome due to their strong reducing ability. In addition, 2-aminoethylphosphonic acid chelates copper ions from tyrosinase, which is metal oxygen, and these things are determined by the presence or absence of tyrosinase activation effect by adding copper ions to the reaction completed solution. Proven. As is clear from this test example, the compound according to the present invention not only has excellent prevention of darkening, but also has extremely high safety, and is therefore extremely suitable for use as a cosmetic product. Moreover, it is compatible with fillers, auxiliaries, and other cosmetic bases.
It is easy to formulate formulations and is extremely suitable as cosmetics, especially skin whitening cosmetics. In particular, when the active ingredients 2-aminoethylsulfinic acid, 2-aminoethylthiosulfonic acid, and 2-aminoethylphosphonic acid are incorporated into a cosmetic base according to the present invention, these can be used alone. may be used or may be used in combination. In particular, as is clear from the above test examples, 2-aminoethylphosphonic acid, which is one of the active ingredients according to the present invention, not only has no safety problems but also has a strong chelate binding force with copper. It inactivates the action of tyrosinase and prevents skin darkening. That is, 2 in the present invention
-The effect of aminoethylphosphonic acid as a cosmetic is to prevent darkening of the skin based on its melanin formation inhibiting effect through chelate formation with copper, and its function is completely different from that of tyrosinase activity inhibitors, which have a reducing effect. belongs to. Therefore, according to the present invention, 2-aminoethylsulfinic acid having anti-tyrosinase action based on reduction action,
By using 2-aminoethylthiosulfonic acid and 2-aminoethylphosphonic acid, which has a chelate-forming effect, two types of active ingredients with different inhibitory mechanisms are mixed, resulting in an extremely outstanding and previously unknown black pigment. This will have the effect of preventing damage. Furthermore, as an active ingredient, the compound represented by the general formula () can be used in combination with other known tyrosinase activity inhibitors, whitening agents, etc. These active ingredient compounds are used as cosmetics, but are not limited in any way by the base material used. Therefore, animal and vegetable fats (oils), higher alcohols, glycols, surfactants, pigments, fragrances, stabilizers and other ingredients that are generally used as cosmetic base materials can be freely used. In addition, there is no particular restriction on the amount of the active ingredient according to the present invention, but it is usually 0.1
% to 10% is preferable. Further, as the preparation method, conventional methods in the art can be used as appropriate. Next, examples of whitening cosmetics according to the present invention will be shown, and the numerical values in the examples represent weight %. Example 1 Whitening lotion 1 Ethanol 5.0 2 Vegetable oil 0.1 3 Polyoxyethylene hydrogenated castor oil 0.5 4 Propylene glycol 5.0 5 2-aminoethylsulfinic acid 1.0 6 Preservatives, fragrances Appropriate amount 7 Purified water Add to make a total volume of 100 ml. Dissolve 1, 2, and 3 and add this to the solution of 4 to 7 to obtain a combed product. Example 2 Whitening pack 1 Polyvinyl alcohol 20.0 2 Ethanol 20.0 3 Propylene glycol 3.0 4 2-aminoethylphosphonic acid 0.5 5 Preservatives, fragrances Appropriate amount 6 Purified water Add to make a total amount of 100 g. 2 is moistened with 1, and this is added to a solution of the remaining ingredients in 6 while heating, and dissolved under stirring to obtain a product. Example 3 Whitening cream (O/W type) 1 Vaseline 2.5 2 Liquid paraffin 10.0 3 Cetostearyl alcohol 12.0 4 Polyoxyethylene sosorbitan monostearate 7.0 5 Sorbitan monostearate 1.0 6 Propylene glycol 5.0 7 2-Aminoethyl sulfin Acid 1.0 8 Calcium pantetheine-S-sulfonate
1.0 9 Preservatives, fragrances Appropriate amount 10 Add purified water to make the total amount 100g. 75 each for oil layers 1 to 5, water layers 6, 9, and 10.
Warm and emulsify at ℃. During cooling, add 7 and 8 and cool to 30℃ to make the product. Example 4 Whitening emulsion 1 Microcrystalline wax 1.0 2 Beeswax 2.0 3 Lanolin 2.0 4 Liquid paraffin 28.0 5 Sorbitan sesquioleate 4.0 6 Tween 80 1.0 7 Aluminum stearate 0.2 8 Glycerin 8.0 9 2-Aminoethylthiosulfonic acid 5.0 10 2 -Aminoethylphosphonic acid 1.0 11 Preservative, fragrance Appropriate amount 12 Purified water Add to make the total amount 100g. 70 each for oil layers 1 to 7, water layers 8, 11, and 12
Warm and emulsify at ℃. During cooling, add 9 and 10 and cool to 30℃ to make the product. Example 5 Whitening emulsion A whitening emulsion product with excellent whitening effect was obtained by repeating the same process as in Example 4 except that 2-aminoethylsulfinic acid was used instead of 2-aminoethylsulfonic acid, which was the ingredient in 9. I got it. Example 6 Whitening emulsion The same treatment as in Example 4 was repeated except that the same amount of 2-aminoethylsulfinic acid was added to 2-aminoethylthiosulfonic acid, which was the ingredient in 9, to obtain a particularly whitening effect. An excellent whitening emulsion product was obtained.

[Brief explanation of the drawing]

Figures 1-3 show 2-aminoethylsulfinic acid, 2-aminoethylthiosulfonic acid, and 2-aminoethylthiosulfonic acid.
1 is a graph illustrating the excellent tyrosinase activity inhibitory effect of aminoethylphosphonic acid. A...Blank B ₀ ...2-Aminoethylsulfinic acid 0.625×10 ^-1 M B ₁ ...Same as above 1.25× ^10-1 M B ₂ ...Same as above 2.5× ^10-1 M B ₃ ...Same as above 5× ^10-1 M C ₀ ...2-Aminoethylthio sulfonic acid 0.625×10 ^-1 M C ₁ ...Same as above 1.25×10 ^-1 M C ₂ ...Same as above 2.5×10 ^-1 M C ₃ ...2-Aminoethylthio sulfonic acid 5×10 ^-1 M D ₀ ...2-aminoethyl phosphonic acid 0.3125×10 ^-1 M D 1 ...Same as above 0.625×10 ^-1 _M D ₂ ...Same as above 1.25×10 ^-1 M D ₃ ...Same as above 2.5×10 ^-1 M

Claims (1)

[Claims] 1 General formula [] NH ₂ CH ₂ CH ₂ X [] (wherein, X is -SO ₂ H, -SO ₂ SH or -PO ₃ H ₂
represents. ) A cosmetic product characterized by containing a compound represented by the following as an active ingredient. 2 Claim 1 characterized in that it is formed by a mixture of two or more compounds represented by the general formula []
Cosmetics listed in section.