JP2999301B2 - Cosmetics - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a cosmetic having a whitening effect containing a dipeptide containing methionine.

[0002]

2. Description of the Related Art Conventionally, hydroquinone and its analogs have been used to reduce the amount of melanin in the skin. These have a strong bleaching effect, but are highly toxic to cells,
It has disadvantages such as formation of irreversible vitiligo on the skin and strong sensitization. As other melanin production inhibitors, L-
Although the use of cysteine and glutathione has been attempted, they are liable to be oxidized, so there is a problem in stability, and there is a peculiar smell, and practical use is difficult.

At present, placenta extract and magnesium L-ascorbic acid-2-phosphate are known as inhibitors of melanin production actually used. However, quantitative analysis of placenta extract from cosmetics is not possible. It is possible, and the L-ascorbic acid-2-phosphate magnesium salt has a problem that the compounding amount must be increased in order to obtain the melanin production inhibitory effect. Is not satisfactory.

In addition, kojic acid and arbutin have recently been used as skin external preparations having a whitening effect, but cannot be said to be practical agents in terms of stability. Methionine has a problem in stability when methionine is used alone in cosmetics, and has drawbacks such as generation of an offensive odor during long-term storage. It is known that methionine and selenomethionine prevent dandruff as a hair cosmetic (Japanese Patent Laid-Open No. 59-71).
No. 11, No. 58-183614, No. 61-2
No. 33608).

[0005] Hair nourishes containing acetylmethionine as a main component are also known (JP-A-49-451 and JP-A-54-46843).

[0006]

There is a need for the development of cosmetics that are safe and stable on the skin and have a high whitening effect.

[0007]

SUMMARY OF THE INVENTION The present invention provides a cosmetic comprising a methionine-containing dipeptide. The dipeptide containing methionine used in the present invention includes methionyl-X or X-methionine (where X is methionine, glycine, serine, cystine, alanine, threonine, valine, phenylalanine, leucine, proline,
In addition to protein-constituting amino acids such as isoleucine, hydroxyproline, asparagine, aspartic acid, glutamine, glutamic acid, arginine, histidine, and lysine, non-protein-constituting amino acids such as β-alanine and ornithine are included.

Specific preferred examples include L-methionyl-L-methionine, L-methionyl-L-histidine, L-phenylalanyl-L-methionine, and L-γ-methionine.
Glutamyl-L-methionine and the like. Dipeptides containing methionine can be prepared by known methods (for example, JPG
in, M. Minitz: Chemistry of the Amino Acids 2 , 891 (1964)
, Journal of the American Chemical
Society (J. Am. Chem. Soc.) 77 , 1067 (1955), etc.].

[0009] The dipeptide containing methionine is usually incorporated in the cosmetic at a ratio of 0.01 to 10.0% by weight.
The cosmetic of the present invention includes various components generally used for cosmetics,
That is, oil, ultraviolet absorber, surfactant, preservative,
Antioxidants, humectants, excipients, fragrances, alcohols, polymers, dyes, pigments, purified water, and the like can be added.

Examples of the oil component include oils and fats such as olive oil , waxes such as beeswax, and squalane.
It is blended at a ratio of 1 to 95 w / w%. Examples of the ultraviolet absorbent include octyl methoxycinnamate and octyl paradimethylaminobenzoate, which are incorporated at a ratio of 0.01 to 4% w / w. Examples of the surfactant include polyoxyethylene (10 mol) stearyl ether, polyoxyethylene (60 mol) hydrogenated castor oil, sorbitan monostearate, glyceryl monostearate and the like.
It is blended at a ratio of 1 to 10 w / w%.

Examples of the preservative include p-hydroxybenzoic acid esters and the like, and are incorporated at a ratio of 0.01 to 1 w / w%. Examples of the antioxidant include vitamin E and the like, and are added at a ratio of 0.001 to 1.0 w / w%. Examples of the humectant include glycerin, 1,3-butylene glycol, mannitol, sorbite, citric acid, and pyrrolidone carboxylic acid, and are blended at a rate of 0.01 to 10 w / w%.

Examples of excipients include mannitol and the like.
And it is blended at a ratio of 0.1 to 99 w / w%. As the fragrance, any fragrance may be used as long as it is usually used for cosmetics, and is blended in a ratio of 0.001 to 1 w / w%. Examples of alcohols include ethanol, 1,3-butylene glycol, propylene glycol and the like.
It is blended at a ratio of 0% w / w.

Examples of the polymer include carboxyvinyl polymer and sodium hyaluronate.
２2 w / w%.

Examples of the dye include tar dyes and the like, and are blended at a ratio of 0.0001 to 1 w / w%. Examples of the pigment include titanium oxide and talc.
It is blended at a ratio of ~ 99 w / w%. The dosage form of the cosmetic is arbitrary, and for example, a dosage form such as a solubilizing type, an emulsifying type or a dispersing type can be used.

The cosmetic products of the present invention include skin care products such as milky lotions, lotions, creams, whitening powders, packs, facial cleansers, and makeup cosmetics such as foundations. Hereinafter, examples and test examples of the present invention will be described.

[0016]

【Example】

Example 1 Preparation of lotion (oil phase component) Perfume 0.05 g Polyoxyethylene (60 mol) hydrogenated castor oil 2.0 g 1,3-butylene glycol 5.0 g (water phase component) L-methionyl-L -Histidine 0.5 g Glycerin 5.0 g Methyl paraben 0.1 g Citric acid 0.1 g Sodium citrate 0.2 g Ethanol 8.0 g Purified water qs 100.0 g (Preparation method) Oil phase component The aqueous phase component was uniformly dissolved, and the oil phase was added to the aqueous phase with stirring to obtain a lotion.

Example 2 Preparation of cream (oil phase component) Squalane 5.0 g Olive oil 3.0 g Hydrogenated lanolin 2.0 g Beeswax 2.5 g Glyceryl monostearate 2.0 g Polyoxyethylene (10 Mol) stearyl ether 2.5 g sorbitan monostearate 1.5 g 1,3-butylene glycol 3.0 g Fragrance (aqueous phase component) Glycerin 5.0 g Carboxyvinyl polymer 0.03 g Triethanolamine 0. 03 g L-Methionyl-L-methionine 0.5 g Methyl paraben 0.3 g Purified water qs 100.0 g (Preparation method) The oil phase component and the water phase component were each heated to 80 ° C. to make uniform, and water was added to the oil phase The phases were added with stirring, emulsified and then cooled to obtain a cream.

Example 3 Preparation of Powder L-Phenylalanyl-L-methionine 2.0 g Methylparaben 0.1 g Gum arabic 0.5 g Citric acid 0.1 g Sodium citrate 0.2 g Mannitol qs Total amount 100.0 g (Preparation method) Each component was uniformly stirred and mixed to obtain a powder.

Test Example 1 Melanin Production Inhibition Test The inhibitory effect of the dipeptide containing L-methionine of the present invention on melanoma cells was compared using L-cysteine and glutathione as controls, using the following test methods. <Test method> L-methionyl-L-histidine, L-methionyl-L
-Eagle MEM medium containing 0 mM, 1 mM, 2 mM and 5 mM of methionine, L-phenylalanyl-L-methionine, L-γ-glutamyl-L-methionine, L-cysteine or glutathione, respectively (inactivated calf fetal serum concentration 1
0%, manufactured by Nissui Pharmaceutical Co., Ltd.)
B-16 melanoma cells derived from mice were cultured at 37 ° C. in the presence of 5% CO ₂ using 5 ml of the medium. A 25 cm ² flask was used for the culture, and 2.5 × 10 ⁵ cells were used.

On the 1st, 4th and 7th days of the culture, the Eagle MEM medium was replaced, and the culture was continued. Culture 9
On the day, the culture was aspirated off to collect the cells, and the cells were washed with Dulbecco's phosphate buffered saline. next,
The protein content and the amount of melanin produced in the cells were measured by the following method, and the amount of melanin produced per protein content was calculated.

That is, the protein content is determined by the microburet method [Analytical Biochemistry].
ochemistry) 9 , 401 (1964)] and the amount of melanin produced is determined by measuring the absorbance of the test solution at 470 nm [Cancer Research 45 , 1474-1478 (198).
5)]. The results are shown in Table 1.

The numerical values in the table are shown as percentages (%) when the additive-free system is taken as 100.

[0023]

[Table 1]

As shown in Table 1, it was confirmed that the L-methionine-containing dipeptide of the present invention has a melanin production inhibitory effect on B-16 melanoma cells as significantly as L-cysteine and glutathione. Was. Test Example 2 Cytotoxicity Test The cytotoxicity of the dipeptide containing L-methionine of the present invention was compared using L-cysteine, kojic acid and glutathione as controls using the following test method. <Test method> L-methionyl-L-histidine, L-methionyl-L
-Eagle MEM medium containing 0 mM, 2 mM and 5 mM of methionine, L-phenylalanyl-L-methionine, L- [gamma] -glutamyl-L-methionine, L-cysteine, kojic acid or glutathione, respectively. %, Manufactured by Nissui Pharmaceutical Co., Ltd.)
Using 5 ml of EM medium, mouse-derived B-16 melanoma cells were cultured at 37 ° C in the presence of 5% CO ₂ . In addition,
A 25 cm ² flask was used for culture, and 2.5 × 10 ⁵ cells were used.

Thereafter, the protein content of the cells was measured in the same manner as in Test Example 1 to determine the amount of cell proliferation. Second result
It is shown in the table. In addition, the numerical value in a table | surface is shown by the percentage (%) when the additive-free system is set to 100.

[0026]

[Table 2]

As shown in Table 2, it was confirmed that the dipeptide containing L-methionine of the present invention had lower cytotoxicity than L-cysteine, kojic acid and glutathione. Test Example 3 Stability test L-methionyl-L-histidine, L-methionyl-L
Methionine, L- phenylalanyl -L-methionine or L-γ-glutamyl-L-methionine at 10 mM each
The solution (50 mM phosphate buffer, pH 6.5) was heated at 80 ° C. for 2 hours or at 120 ° C. for 10 minutes, and the remaining amount of the compound was analyzed by HPLC (UV absorption at a wavelength of 220 nm).
did.

Glutathione was subjected to the same treatment as above as a control. The results are shown in Table 3.

[0029]

[Table 3]

As shown in Table 3, the dipeptide containing L-methionine of the present invention was more stable than glutathione. Test Example 4 Sensory test L-methionyl-L-histidine, L-methionyl-L
- Methionine, L- phenylalanyl -L- methionine, L-.gamma.-glutamyl -L- methionine, their specific odor using seven expert panelists for a 1% aqueous solution of L over system <br/> in or glutathione Was evaluated.

The results are shown in Table 4.

[0032]

[Table 4]

As shown in Table 4, the L-methionine-containing dipeptide of the present invention has no peculiar odor and is a convenient compound to be formulated as a cosmetic.

[0034]

According to the present invention, it is possible to provide a cosmetic which is safe, has good stability and has an excellent whitening effect on the skin.

Claims (2)

(57) [Claims] 1. A cosmetic comprising a dipeptide represented by methionyl-X or X-methionine (wherein X represents an amino acid residue). 2. X is methionine, glycine, serine, cystine, alanine, threonine, valine, phenylalanine, leucine, proline, isoleucine, hydroxyproline, asparagine, aspartic acid, glutamine, glutamic acid, arginine, histidine, lysine,
The cosmetic according to claim 1, which is an amino acid residue selected from β-alanine or ornithine.