JPH09301990A - Sesamol glucide and preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new glucide useful as a melanism inhibitor excellent in inhibitory effect on melanism and high in safety and for a preparation of external use for skin so as to lighten the skin, by bonding a saccharide to sesamol contained in a sesame oil. SOLUTION: This new sesamol glucide comprises the formula (R is a group selected from the residues of a monosaccharide or an oligosaccharide), is a melanism inhibitor excellent in inhibitory effect on melanism and high in stability and safety and is useful for a preparation for external use for skin so as to lighten the skin. The glucide is obtained by stirring sesamol separated from a sesame oil in a dehydrated toluene in the presence of glucose pentaacetate and molecular sieves at a room temperature for about one hour, adding a solution of boron trifluoride in diethyl ether, further stirring the solution for three hours, filtering the reaction solution, extracting the filtrate with ethyl acetate, distilling away the solvent from the extracted solution to give sesamol tetraacetyl glucoside and further deacetylating the substance.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel melanin production inhibitor and a skin external preparation containing the same. More specifically, it relates to a sesamol glycoside that can be incorporated into cosmetics, quasi drugs, pharmaceuticals and the like for the purpose of whitening the skin.

[0002]

BACKGROUND OF THE INVENTION Sesamol is already known as one of the compounds having strong antioxidant and antibacterial properties contained in sesame oil (Agric.
Biol. Chem., 301, Vol. 49, No. 2, 1985.
JP-A-61-238714 and JP-A-61
No. 238718).

Studies have also been conducted on the antioxidant power of sesamol-like compounds (30th Oil Chemistry Debate, Oil Chemistry Research Presentation, Abstracts, p. 29, 1991). It has not been examined. Also, there is a report that it has a strong melanin production inhibitory effect (Japanese Patent Laid-Open No. 62-56411). However, since there is a problem that it is easily deteriorated by heat, light, etc., the amount and range of use have been limited.

Sesamol and its derivatives and similar compounds are effective in the treatment and prevention of liver diseases (JP-A-2-255616, JP-A3-1).
No. 84973), and further, it has been reported that it has a strong anti-cancer effect without side effects (Japanese Patent Laid-Open No. 6-2).
No. 79432).

As described above, it is known that various sesamol derivatives and similar compounds have excellent physiological activity, but there is no report on the glycoside derivative according to the present invention.

Conventionally, hydroquinone and hydroquinone monobenzyl ether (NBEH) have been used as compounds having a strong melanin production-inhibiting effect, but these cause denaturation and death of pigment cells and impair the original physiological function of the skin. There are defects that cause side effects such as irreversible vitiligo, pigment abnormalities, and rashes. In addition, glycosides with improved stability and safety of hydroquinone are also known as melanin production inhibitors (Proc.Jpn.Soc.Invest.Dermat).
ol., 12, p138, 1988 and JP-A-60-56912), the effect is not satisfactory.

An object of the present invention is to provide a melanin production inhibitor which exhibits excellent effects on the inhibition of melanin production and is highly stable and safe, as well as a skin external preparation containing the same.

[0008]

[Means for Solving the Problems] In view of the above circumstances, the present inventors have conducted extensive studies to develop a novel sesamol derivative having a strong melanin production inhibitory effect and high stability and safety. The present inventors have completed the present invention by successfully synthesizing the above-mentioned sesamol glycoside and found that the compound has a melanin production inhibitory action. Furthermore, they have succeeded in providing a skin external preparation containing the same. That is, the present invention is a sesamol glycoside represented by the following general formula and a skin external preparation containing the same.

[0009]

Embedded image

(In the formula, R is a group selected from residues of monosaccharides and oligosaccharides.)

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below.

As a method for synthesizing the sesamol glycoside of the present invention, a method already known as a method for synthesizing arbutin (USP 3201385) can be used. For example, it can be easily obtained by condensing sesamol and an acetylated sugar in an organic solvent such as toluene using boron trifluoride, phosphorus oxychloride or the like as a catalyst, and then eliminating the acetyl group in the presence of an alkali.
By this synthetic method, the sesamol glycoside is obtained as white powder crystals.

The sugar residue of the sesamol glycoside used in the present invention is a reducing monosaccharide or oligosaccharide, and specifically, monosaccharides such as glucose, galactose, xylose, mannose and N-acetylglucosamine, Examples thereof include disaccharides such as maltose, cellobiose, and gentiose. The glycoside of the present invention has an isomer having an α bond and a β bond, and either of them or a mixture thereof can be used.

The external preparation for skin containing the sesamol glycoside of the present invention may be used, if necessary, to the extent that its effect is not impaired.
Various components generally used as a composition for external preparation for skin,
That is, oil, surfactant, moisturizer, thickener, preservative,
Antioxidants, ultraviolet absorbers, fragrances, dyes and the like may be combined and blended.

The external preparation for skin of the present invention can be in any dosage form such as ointments, lotions, emulsions, creams, packs, granules and base make-up.

The amount of the compound is 0.001 to 10.0% by weight as a result of studying the range for achieving the object of the present invention.
Is preferable, and more preferably 0.1 to 5.0% by weight. Since the sesamol glycoside of the present invention is water-soluble, it can be easily used for oral preparations.

[0017]

The present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. Further, wt% shown in the examples means% by weight.

Example 1 2.76 g (20 mmol) of sesamol, 8 g (20 mmol) of glucose pentaacetate and 2 g of molecular sieves were added to 40 ml of dehydrated toluene, and the mixture was stirred at room temperature for about 1 hour and then boron trifluoride diethyl was added. 1 ml of an ether solution was added, and the mixture was further stirred for 3 hours. After adding 20 ml of water, the molecular sieves were filtered off. The organic layer was extracted from the filtrate with ethyl acetate. The ethyl acetate layer was washed with 1N sodium hydroxide to remove unreacted sesamol. The ethyl acetate layer was washed with purified water and dried over sodium sulfate. After removing sodium sulfate, the organic solvent was removed under reduced pressure to obtain sesamol tetraacetylglucoside.

The sesamol tetraacetyl glucoside was deacetylated with sodium methoxide, which is a conventional method, and then neutralized with an ion exchange resin (Amberlite). After the ion exchange resin was filtered off, the solvent was removed under reduced pressure to obtain 3.4 g of sesamol glucoside (β form). This structure was confirmed by ¹ H and ¹³ C-NMR spectrum and infrared absorption spectrum. FIG. 1 shows the ¹ H-NMR spectrum of the sesamol glucoside (β-form) of the present invention. In addition, FIG. 2 shows the sesamol glucoside (β
¹³ C-NMR spectrum of (form).

Example 2 The reaction was carried out in the same manner as in Example 1 except that 8 g of glucose pentaacetate was changed to 7.2 g of xylose tetraacetate to obtain 2.8 g of sesamol xyloside (β form). This structure was confirmed by ¹ H and ¹³ C-NMR spectrum and infrared absorption spectrum. FIG. 3 shows the ¹ H-NMR spectrum of the sesamol xyloside (β-form) of the present invention. In addition, FIG. 4 shows the sesamol xyloside (β
¹³ C-NMR spectrum of (form).

Example 3 The reaction was carried out in the same manner as in Example 1 except that 8 g of glucose pentaacetate was changed to 8 g of galactose pentaacetate to obtain 2.7 g of sesamol galactoside (β-form). This structure was confirmed by ¹ H and ¹³ C-NMR spectrum and infrared absorption spectrum. Further, FIG. 5 shows an infrared absorption spectrum of the sesamol galactoside (β form) of the present invention.

Example 4 (Melanin production inhibition test) The compounds obtained in Examples 1 to 3 were subjected to a melanin production inhibition test. The melanin production suppression test in pigment cells is
B16 melanoma cells (3 × 10 ⁵ cells) were spread on a plastic plate with a diameter of 90 mm, and at the same time 3 × 1 of the test sample
It was added at a concentration of 0 ^-5 M (test concentration was standardized to be a molar concentration) and cultured for 72 hours. The culture was performed in a MEM (containing 2 mM theophylline) medium containing 10% FBS. After culturing, according to a conventional method, after removing the cells and washing,
Centrifugation was performed. The obtained cells were washed with 5% TCA, ethanol: ether = 3: 1, and then with ether. After drying, the amount of melanin was measured by dissolving in Solen 350 (a cell lysing agent, manufactured by Packard) and measuring the absorbance at 400 nm. The lower the absorbance, the greater the effect of suppressing melanin production. As a comparative example, a hydroquinone glycoside (arbutin) known to have a melanin production inhibitory effect was used. Table 1 shows the measurement results.

[0023]

[Table 1]

As shown in Table 1, it was revealed that the sesamol glycoside of the present invention suppresses melanin production without hindering cell growth. Further, it was found that the degree of absorption was lower than that of arbutin, which is widely used in pharmaceuticals, cosmetics, etc., that is, the melanin production inhibitory effect was excellent.

Example 5 (Stability test) The stability of the sesamol glycosides and sesamol obtained in Examples 1 to 3 was compared. Test method is 100 mg of each sample 5
It was added to 10 ml of 0% ethanol aqueous solution and sealed in a transparent glass bottle. After left in the sun for about 1 month, the color tones of the solutions were compared. In the evaluation, those with no discoloration were evaluated as ◯, and those with discoloration were evaluated as x. Table 2 shows the results.

[0026]

[Table 2]

As shown in Table 2, it was revealed that the sesamol glycoside of the present invention is superior in stability to sesamol. As a result, it was found that blending into various preparations such as pharmaceuticals and cosmetics became easy.

Examples 6 to 8 and Comparative Example 1 (Cream) According to the formulation shown in Table 3, creams were prepared by a conventional method.

[0029]

[Table 3]

Examples 9 to 11 and Comparative Example 2 (Lotion) Lotions were prepared by a conventional method according to the formulation shown in Table 4.

[0031]

[Table 4]

Regarding Examples 6 to 11 and Comparative Examples 1 and 2,
(1) Skin lightness recovery test and (2) Whitening practical test were conducted. The test method and evaluation method are as follows.

(1) Skin lightness recovery test [0033] The skin on the inner arm of the upper arm of 20 subjects was irradiated with ultraviolet rays in the UVA and UVB regions at the minimum erythema dose for 3 consecutive days. ) Was measured. The sample was applied three times a day to the area corresponding to one-half of the skin area irradiated with ultraviolet rays three times a day for four weeks continuously, and nothing was applied to the remaining one-half the area. The brightness of each part was measured 4 weeks after the ultraviolet irradiation, and the difference in brightness was calculated by subtracting the reference brightness. In order to compare the difference in brightness between the sample-coated part and the non-coated part, the value obtained by subtracting the difference in brightness of the non-coated part from the difference in brightness of the sample-coated part was defined as the recovery degree, and Table 5 below.
It was judged according to the standard.

[0034]

[Table 5]

(2) Whitening Practical Test For a group of 20 subjects who are often exposed to sunlight outdoors,
The sample was applied to the face once in the morning and in the evening, and was continuously used for 4 months from May to August. After 4 months, the effect of improving fairness, stains, freckles, etc. was evaluated according to the criteria shown in Table 6 below.

[0036]

[Table 6]

Table 7 shows the results of (1) skin lightness recovery test and (2) whitening practical test conducted on Examples 6 to 11 and Comparative Examples 1 and 2. In addition, evaluation was shown by the number of people of each criterion among 20 test subjects.

[0038]

[Table 7]

From Table 7, it is clear that the external preparation for skin containing the sesamol glycoside of the present invention prevents stains and freckles and is excellent in whitening effect.

[0040]

Industrial Applicability As described above, the sesamol glycoside of the present invention has a strong melanin production inhibitory effect and exhibits excellent stability. Furthermore, the skin external preparation containing the sesamol glycoside of the present invention can provide a skin external preparation having a high melanin production suppressing effect. The sesamol glycoside of the present invention can also be expected as an antibacterial agent or an antioxidant.

[Brief description of drawings]

FIG. 1 is a diagram showing a ¹ H-NMR spectrum of sesamol glucoside (β-form) obtained in Example 1 of the present invention.

FIG. 2 is a diagram showing a ¹³ C-NMR spectrum of sesamol glucoside (β-form) obtained in Example 1 of the present invention.

FIG. 3 is a diagram showing a ¹ H-NMR spectrum of sesamol xyloside (β-form) obtained in Example 2 of the present invention.

FIG. 4 is a diagram showing a ¹³ C-NMR spectrum of sesamol xyloside (β-form) obtained in Example 2 of the present invention.

FIG. 5 is a diagram showing an infrared absorption spectrum of sesamol galactoside (β-form) obtained in Example 3 of the present invention.

Claims (2)

[Claims] 1. The following general formula: (In the formula, R is a group selected from residues of monosaccharides and oligosaccharides.) A sesamol glycoside. 2. An external preparation for skin comprising the sesamol glycoside according to claim 1.