JPH10265325A - Melanin formation suppressant and skin whitening cosmetic material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject suppressant which is high in safety and possesses the excellent suppressive effect on melanin formation and the effect decreasing pigmentation on skin caused by exposure to ultraviolet ray by using a specific compound as an active ingredient. SOLUTION: This suppressant for melanin formation contains a raspberry ketone of formula I (R is H and an 2-20C acyl) and its derivative and rhododendrol of formula II and its derivative as active ingredients. As the compound of formula I, hexanoylraspberry ketone and the like are illustrated, and as the compound of formula II, hexanoylrhododendrol and the like can be illustrated. This suppressant for melanin formation may be formulated with a skin whitening cosmetic material decreasing pigmentation in an amount of 0.05-10.0 wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a melanin production inhibitor and a whitening cosmetic containing the same. More specifically, melanin production is highly safe and can be combined with cosmetics, quasi-drugs, and pharmaceuticals for the purpose of improving skin pigmentation (spots, freckles, etc.) caused by exposure to ultraviolet light. Related to inhibitors.

[0002]

BACKGROUND OF THE INVENTION Blots and freckles are those in which the balance between production and excretion of melanin is lost and melanin is excessively accumulated in epidermal cells [Yutaka Mishima et al., Fragrance Journal, 17 (1), p25, 1989]. . These causes can be varied, including inflammation, hormonal balance, and genetic factors, but are facilitated by the effects of ultraviolet radiation. Whitening agents alleviate the increased pigmentation. Among them, ascorbic acid or a derivative thereof, placenta extract, hydroquinone derivative (arbutin), kojic acid and the like are known as those applied for whitening cosmetics, and whitening cosmetics containing these are proposed. I have.

[0003] However, although these whitening agents have an effect of suppressing the production of melanin, many of them have a problem in safety. Further, even when a whitening cosmetic containing these whitening agents is applied, an effect which is not always satisfactory enough for improvement of spots and freckles cannot be obtained.

[0004] Melanin is produced by melanosomes, the organelles in melanocytes (pigment cells) in the basal layer of the epidermis. After that, it is transferred to keratinocytes (epidermal cells) and undergoes keratinization while undergoing decomposition within the keratinocytes, and eventually disappears from the skin along with keratinocyte desquamation (Masayoshi Kiyoji, a modern dermatologist, 3B, 97 pages,
Nakayama Shoten, 1982).

[0005] Therefore, since the cause of spots and freckles is complex, melanin not only suppresses the production of melanin, but also prevents inflammation which causes pigmentation and activates metabolism to cause melanin to develop in the skin. It is important to prevent it from staying inside and to restore skin function damaged by ultraviolet rays or the like.

[0006]

SUMMARY OF THE INVENTION An object of the present invention is to provide a melanin production inhibitor having a high safety and an excellent melanin production inhibitory effect, and to provide skin pigmentation caused by exposure to ultraviolet rays. An object of the present invention is to provide a whitening cosmetic having an excellent effect of improving (spots, freckles, etc.).

[0007]

Means for Solving the Problems In view of the above-mentioned circumstances, the present inventors have a melanin production inhibitory effect,
As a result of intensive studies to develop a highly safe melanin production inhibitor, specific compounds have a strong melanin production inhibitory effect and skin pigmentation caused by exposure to ultraviolet rays (stains, freckles, etc.) Have also been found to have the effect of improving That is, the present invention provides a melanin production inhibitor comprising raspberry ketone represented by the following general formulas (1) and (2), a derivative thereof, rhododendrol and a derivative thereof, and a whitening cosmetic containing the same. It is.

[0008]

Embedded image

(Wherein R is a hydrogen atom or a group having 2 to 2 carbon atoms)
20 acyl groups. )

[0010]

Embedded image

(Where R is a hydrogen atom or a group having 2 to 2 carbon atoms)
20 acyl groups. )

[0012]

Embodiments of the present invention will be described below in detail.

The raspberry ketone used in the present invention is used as a fragrance, and it is known that rhododendrol is contained in Acer nikoence Maxim. However, the use of raspberry ketone and rhododendrol is limited due to their unique aroma. Therefore, in order to reduce the peculiar aroma, it is used by acylation. Some of these acylated derivatives are known substances, but there is no description that the reported known substance has a melanin production inhibitory action.

The method for obtaining the acylated derivative of raspberry ketone of the present invention can be obtained by a method already known as acylation of a phenol compound. For example, 4- (p-hydroxyphenyl) -2-butanone (hereinafter abbreviated as raspberry ketone) in pyridine
And acid chloride can be easily obtained. Further, by reducing the ketone group of the obtained acylated raspberry ketone with sodium borohydride, an acylated rhododendrol can be obtained. In addition, the rhododendrol and the acylated rhododendrol have optical isomers.
The body alone or a mixture thereof can be used.

The acyl group defined in the formula in the present invention is not particularly limited as long as it is generally used, but a linear saturated acyl group is preferred from the viewpoint of stability and ease of synthesis. .

The melanin production inhibitor of the present invention is used
It can be incorporated into quasi-drugs and cosmetics. In particular, it is suitable to be incorporated into a whitening cosmetic which improves pigmentation. In addition, the melanin production inhibitor of the present invention can be blended into a composition for external use or a composition for internal use.

The amount of the melanin production inhibitor of the present invention varies depending on the system used, and cannot be specified unconditionally. However, as is apparent from the following examples, the concentration of the melanin production inhibitor is equal to or considerably lower than that of the existing substances of this type. And 0.05 to 10.0% by weight can be used.

The whitening cosmetic composition of the present invention may optionally contain
Oils and fats, moisturizers, pigments, pigments, surfactants, antioxidants, ultraviolet absorbers, preservatives, which are usually incorporated in skin external preparations such as pharmaceuticals, quasi-drugs, and cosmetics And water-soluble polymers, resins and the like can be appropriately compounded.

[0019] In addition, any dosage form such as ointments, lotions, emulsions, creams, packs, granules and the like can be used.

[0020]

EXAMPLES Next, synthetic examples, test examples, and formulation examples (whitening cosmetics) will be described as examples for clarifying the effect of the compound of the present invention on the inhibition of melanin production.

As specific examples of the synthesis method, a method for synthesizing hexanoyl raspberry ketone and hexanoyl rhodendrol will be described below, but the method for synthesizing the melanin production inhibitor used in the present invention is not limited thereto.

Synthesis Example 1 Synthesis of Hexanoyl Raspberry Ketone 8.2 g of raspberry ketone was dissolved in 20 ml of pyridine. After gradually adding 8.1 g of hexanoyl chloride with stirring, the mixture was left at room temperature for 1 hour. Next, cooled 3%
After adding 500 ml of an aqueous hydrochloric acid solution, the mixture was extracted with 200 ml of hexane. The hexane layer was washed with cooled distilled water and dried over magnesium sulfate. The hexane layer was concentrated under reduced pressure to obtain 12.3 g of a transparent oil. The obtained transparent oil was purified by a silica gel column (hexane / ethyl acetate = 8/1) to obtain 10.9 g of hexanoyl raspberry ketone used in the present invention. This structure was confirmed by infrared absorption spectrum and NMR measurement. FIG. 1 shows ¹³ C—N of hexanoyl raspberry ketone.
3 shows an MR spectrum.

Synthesis Example 2: Synthesis of hexanoyl rhododendrol 5.0 g of hexanoyl raspberry ketone obtained in Synthesis Example 1 was reduced using sodium borohydride according to a conventional method, and the obtained oil was obtained. Purify on a silica gel column (hexane / ethyl acetate = 8/1) and use in the present invention.
4.1 g of hexanoyl rhododendrol were obtained. This structure was confirmed by infrared absorption spectrum and NMR measurement. FIG. 2 shows the ¹³ C—N of hexanoyl rhododendrol.
3 shows an MR spectrum.

In addition, according to Synthesis Example 1, "Sample" in Table 1 was used.
The compounds according to the invention indicated in the column are obtained.

Test Example 1 Melanin Production Inhibition Test [In Vitro Test] In the melanin production inhibition test using pigment cells, B16 melanoma cells (3 × 10 ⁵ cells) were spread on a 90 mm diameter plastic plate and tested simultaneously. The sample was added at a concentration of 3 × 10 ⁻⁵ M (the test concentration was unified to the molar concentration), and the cells were cultured for 72 hours. The culture was performed in a MEM (containing 2 mM theophylline) medium containing 10% FBS. After completion of the culture, the cells were detached and washed according to a conventional method, and then centrifuged. The obtained cells were washed with 5% TCA, ethanol: ether = 3: 1, and then with ether. After drying, the melanin content was measured by dissolving in Solen 350 and measuring the absorbance at 400 nm. The lower the absorbance, the greater the melanin production inhibitory effect. As a comparative example, arbutin, which is known to have a melanin production inhibitory effect, was used.

Table 1 shows the measurement results.

[0027]

[Table 1]

From the results shown in Table 1, it was revealed that the melanin production inhibitor of the present invention inhibits melanin production without inhibiting cell proliferation (meaning high safety). In addition, it was found that the degree of absorbance was lower than that of arbutin, which is widely used in pharmaceuticals, cosmetics, and the like, that is, the melanin production inhibitory effect was excellent. this,
From the results of the in vitro test, it was confirmed that the specific compound of the present invention can be used as a main ingredient of whitening cosmetics, for example, in pharmaceuticals, quasi-drugs, cosmetics, and the like.

Test Example 2: Skin Pigmentation Recovery Test [In Vivo Test] Two ultraviolet irradiation sites were set (2 × 2 cm) on the inner skin of the upper arm of a group of 20 subjects, and the minimum erythema amount was measured. Irradiation was performed continuously for 3 days with ultraviolet rays in the middle wavelength region (Dermalei N-DMR, manufactured by Toshiba Medical Products). From the end of the irradiation, one was coated with the sample preparation three times a day for four consecutive weeks, and the other was coated with the base (the main preparation was removed from the preparation). Four weeks after the ultraviolet irradiation, the degree of pigmentation between the base application part and the sample preparation application part was compared by visual judgment of each part. According to the evaluation criteria in Table 2, the degree of recovery of pigmentation was evaluated in comparison with the base coated part. In addition, evaluation is shown by the average value of the evaluation point of 20 persons.

[0030]

[Table 2]

Examples 1 to 3 and Comparative Example 1 (Cream) Creams were prepared according to the recipe shown in Table 3 according to a conventional method.

[0032]

[Table 3]

Table 4 shows the results of the skin pigmentation recovery tests of Examples 1 to 3 and Comparative Example 1.

[0034]

[Table 4]

From Table 4, it is clear that the examples of the present invention are excellent in the effect of improving spots and freckles. In particular, Example 1 in which raspberry ketone was blended and Example 3 in which rhodendrol was blended had remarkable effects. During the test period, no skin irritation reaction was observed at the site where the sample preparation was applied to the test subject, confirming that the product of the present invention is safe even in the form of the preparation.

Example 4 (Emulsion) An emulsion was prepared according to the formulation shown in Table 5 according to a conventional method.

[0037]

[Table 5]

Example 5 (Lotion) A lotion was prepared according to the formulation shown in Table 6 according to a conventional method.

[0039]

[Table 6]

The results of the skin pigmentation recovery tests of Examples 4 and 5 are shown in Table 7.

[0041]

[Table 7]

From Table 7, it is clear that Examples 4 and 5 are excellent in the effect of improving spots and freckles.

[0043]

As described above, the compound of the present invention comprises
It exhibited an excellent melanin production inhibitory effect, and its safety was also high. Furthermore, the preparations containing the compound of the present invention exhibited an excellent effect of improving skin pigmentation (staining, freckles, etc.) caused by exposure to ultraviolet rays. Therefore, the compounds of the present invention can be used in cosmetics and quasi-drugs that prevent the formation of spots, freckles, etc. due to excessive production of melanin due to ultraviolet rays, etc. Obviously, it provides a possible and useful melanogenesis inhibitor.

[Brief description of the drawings]

FIG. 1 is a diagram showing a ¹³ C-NMR spectrum of hexanoyl raspberry ketone obtained in Synthesis Example 1 of the present invention.

FIG. 2 is a diagram showing a ¹³ C-NMR spectrum of hexanoyl rhododendrol obtained in Synthesis Example 2 of the present invention.

Claims (3)

[Claims] [Claim 1] The following general formula (1) (Wherein, R is a hydrogen atom or an acyl group having 2 to 20 carbon atoms). 2. The following general formula (2): (Wherein, R is a hydrogen atom or an acyl group having 2 to 20 carbon atoms). 3. A whitening cosmetic comprising the melanogenesis inhibitor according to claim 1 or 2.