JP4854939B2 - Melanin production inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a melanogenesis inhibitor having high melanogenesis inhibitory or bleaching effect and substantially free of discoloration and toxicity to mammals, especially humans, through solving problems in view of the fact that although there are many unknown causes of skin fleckles and rough skin, pigmentation by melanogenesis has been cited as one of these factors, and various substances having the effects of preventing fleckles and rough skin have been used so far, but these substances are problematic in terms of discoloration, efficacy, etc. <P>SOLUTION: The melanogenesis inhibitor comprises as active ingredient one or more substances selected from the group consisting of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one-bound saponin. <P>COPYRIGHT: (C)2006,JPO&amp;NCIPI

Description

  The present invention relates to a melanin production inhibitor containing one or more specific compounds represented by Chemical Formula 1 as active ingredients, and more preferably 2,3-dihydro-3,5-dihydroxy-6 having a whitening effect. -Methyl-4H-pyran-4-one, 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one and 2,3-dihydro-2,5-dihydroxy-6-methyl The present invention relates to a melanin production inhibitor containing one or more selected from the group of -4H-pyran-4-one-bonded-saponin as an active ingredient, and further to a cosmetic containing the melanin production inhibitor.

  Although there are many unclear points as the cause of skin spots, freckles, and rough skin, pigmentation due to melanin production is cited as one of the causes. Arbutin and the like have already been known as substances having a beautifying effect, an effect of preventing spots and freckles, and an effect of preventing rough skin (for example, see Patent Document 1), and are intended to prevent various whitening cosmetics and spots and freckles. It is applied as a base material for quasi drugs. In addition, the whitening effect and skin beautifying effect of brown sugar and its extract have long been well known (see, for example, Patent Documents 2 to 5). Further, as an oxygen-containing monocyclic compound having a whitening effect, kojic acid (see, for example, Patent Document 6), 3-hydroxy-4-pyranone, or 3-acyloxy-4-pyranone (see, for example, Patent Document 7). )It has been known.

JP 60-56912 A Japanese Patent Publication No.59-48809 JP 61-236728 A Japanese Patent Laid-Open No. 2002-212048 JP-A-5-310547 Japanese Examined Patent Publication No. 56-18869 Japanese Examined Patent Publication No.59-35884

However, in Japanese Patent Publication No. 59-48809, Japanese Patent Laid-Open No. 61-236728, Japanese Patent Laid-Open No. 2002-212048, etc., the component extracted from brown sugar is a colored component (sugar pigment) or a natural black component. Cosmetics prepared by blending these materials are markedly colored and are difficult to use as general cosmetics. Further, kojic acid, 3-hydroxy-4-pyranone, 3-acyloxy-4-pyranone, etc., which are oxygen-containing monocyclic compounds having a whitening action, have problems in safety and effectiveness, and are satisfactory whitening. There was a problem that had no effect.

  Therefore, the present inventors have conducted intensive studies and found that a substance completely different from a conventionally known compound having a whitening effect was unexpectedly found in extraction studies from soybean, brown sugar, and molasses. It was also found that the melanin production inhibitory effect was excellent.

  Accordingly, an object of the present invention is to provide a melanin production inhibitor that has little coloring problem even when added to cosmetics, has little toxicity to mammals, particularly humans, and has a high melanin production inhibitory effect or whitening effect. That is.

That is, the gist of the present invention relates to a melanin production inhibitor containing one or more specific compounds represented by Chemical Formula 1 as active ingredients, and more specifically 2,3-dihydro-3,5 having a whitening effect. -Dihydroxy-6-methyl-4H-pyran-4-one, 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one and 2,3-dihydro-2,5-dihydroxy The present invention relates to a melanin production inhibitor containing one or more selected from the group of -6-methyl-4H-pyran-4-one-bonded-saponin as an active ingredient, and further to a cosmetic containing the melanin production inhibitor.

  With the melanin production inhibitor of the present invention, there are almost no problems of coloring even when added to cosmetics, there is almost no toxicity to mammals, particularly humans, and a high melanin production inhibitory effect or whitening effect can be obtained. Played. Furthermore, a cosmetic with a high whitening effect can be obtained by the melanin production inhibitor of the present invention.

  The melanin production inhibitor of the present invention has the following general formula (1):

但し、式中、Ｒ１は水素原子（Ｈ）又は水酸基（ＯＨ）あるいはサポニンを示す。Ｒ２は水素原子（Ｈ）又は水酸基（ＯＨ）示す
で表される化合物の１種又は２種以上を有効成分とするメラニン生成抑制剤に関し、さらに当該メラニン生成抑制剤を含む化粧品に関する。

In the formula, R1 represents a hydrogen atom (H), a hydroxyl group (OH) or saponin. R2 relates to a melanin production inhibitor containing one or more compounds represented by hydrogen atom (H) or hydroxyl group (OH) as an active ingredient, and further relates to a cosmetic containing the melanin production inhibitor.

  Examples of the compound represented by the general formula (1) include 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, soybean DDMP saponin (2,3-dihydro-2,5 -Dihydroxy-6-methyl-4H-pyran-4-one-linked-saponin) and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one, -Dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one is most preferred.

  2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one is a safe substance that is recognized as a fragrance for food additives, and is a Maillard reaction of sugar or fructose with alanine. It is a substance that is produced and is also contained in baked goods, and is also contained in molasses and brown sugar. Furthermore, 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one -Binding-Saponin (DDMP saponin) is a substance that is contained in soybeans and ingested as natto, tofu, miso, etc. and is safe to eat. These compounds can be obtained by a general chemical synthesis method, but can also be obtained by extraction from raw materials such as soybean, brown sugar and molasses. These substances having a whitening effect may be used alone or in combination of two or more.

  Examples of the raw material used in the present invention include soybeans such as mung beans, yellow beans, and black beans, brown sugar, and molasses. Such raw materials may be used alone or in combination of two or more.

2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one may be a commercially available fragrance for food additives, and may be a Maillard of sugar and alanine. What was prepared by the existing method (The Journal of Japan Society for Food Science and Technology, Vol. 2, No. 1, pp. 20-25, 1995) which is extracted from the reaction product with water and fractionated by HPLC may be used. Furthermore, it can also be obtained by extracting from molasses or brown sugar with alcohol and separating and purifying with HPLC or the like.
2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one or 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one- from soybean The method for extracting bound-saponin (soybean DDMP saponin) is not particularly limited, but a fraction extracted from crushed soybeans with 70% aqueous ethanol solution is extracted with aqueous butanol solution, and the butanol layer is further separated by HPLC. It is also possible to use an image prepared by an existing method (Biosci. Biotech. Biochem., Vol. 57, No. 4, 546-550, 1993).

  Examples of a method for extracting 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one from molasses or brown sugar include the following methods.

(1) Dissolving molasses in water and removing impurities by centrifugation or filtration;
(2) After bringing the solution obtained in step (1) into contact with the adsorbent, the adsorbent is washed with water to sufficiently remove sugar, and then adsorbed with 15 to 35 wt% alcohol. Eluting the substance;
(3) A step of separating the butanol layer by partitioning the eluent obtained in step (2) with butanol and water;
(4) a step of eluting the butanol layer obtained in step (3) with 5-15 wt% alcohol using a gel filtration column; and (5) the eluate obtained in step (4) is reversed phase Applying to a system column and eluting with 10 to 20% by weight of alcohol,
A fraction containing 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one can be obtained by a method comprising Furthermore, if desired, the alcohol contained in the fraction can be evaporated to obtain a concentrate.

Alternatively, instead of step (3) in the method,
(3 ′) a step of eluting the adsorbent with an alcohol having a concentration of 2 to 10% by weight using the adsorbent column from the eluent obtained in step (2),
2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one can be obtained by a method comprising Furthermore, if desired, the alcohol contained in the fraction can be evaporated to obtain a concentrate.

  As the adsorbent used in the step (2), for example, an aromatic resin synthetic adsorbent can be used. For example, a porous synthetic resin polymerized from styrene and divinylbenzene can be used. Examples of such a resin include Amberlite XAD type (Rohm and Haas) and HP type (Mitsubishi Kasei).

  As the adsorbent for the column used in the step (3 ′), a silica-based packing material in which an octadecyl group is chemically bonded can be used, COSMOSIL type (manufactured by Nacalai Tesque), Develosil type (manufactured by Nomura Chemical), Examples include TSKgel type (manufactured by Tosoh Corporation), YMC-pack type (manufactured by YMC Corporation), MCI GEL ODS type (manufactured by Mitsubishi Chemical Corporation), and the like.

  As the filler used in the gel filtration column in the step (4), a filler capable of fractionating a molecular weight of 1000 to 7000 is desirable, Toyoperl HW-40C (manufactured by Tosoh Corp.), Sephadex G-25 (manufactured by Pharmacia Corp.) Etc.

  As a packing material used for the reverse phase system column in the above step (5), a silica gel system chemically bonded with an octyl group can be used. Examples include a type (manufactured by Tosoh Corporation), a YMC-pack type (manufactured by YMC Corporation), an MCI GEL OTS type (manufactured by Mitsubishi Chemical Corporation), and a Lichloroprep type (manufactured by Merck).

  Examples of the alcohol used in the steps (2), (3 '), (4) and (5) include lower alcohols such as methanol, ethanol, isopropanol, n-butanol and isobutanol. The concentration of the alcohol used in each step varies depending on the column used in each step. In step (2), 15 to 35% by weight is preferable, and 20 to 30% by weight is more preferable. 3 ′) is preferably 2 to 10% by weight, more preferably 3 to 7% by weight. In step (4), 5 to 15% by weight is preferable, and 7 to 13% by weight is more preferable. ) Is preferably 10 to 20% by weight, more preferably 13 to 17% by weight.

  As described above, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one can be obtained. As the melanin production inhibitor of the present invention, the fraction obtained by the extraction method may be used as it is, or, if desired, the obtained fraction may be further purified by preparative HPLC such as a reverse phase column. The product may be used.

  In order for the melanin production inhibitor of the present invention to have an effect of inhibiting melanin production, one or more of the specific compounds represented by Chemical Formula 1 in the melanin production inhibitor, preferably 2,3-dihydro-3 , 5-Dihydroxy-6-methyl-4H-pyran-4-one, 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one and 2,3-dihydro-2,5 One or more selected from the group of -dihydroxy-6-methyl-4H-pyran-4-one-bonded-saponin is preferably 1 wt% or more, more preferably 10 wt% or more, water, ethanol, It is desirable to be dispersed and dissolved in a solvent such as glycene or propylene glycol.

  One or more of the specific compounds represented by Chemical Formula 1 in the melanin production inhibitor of the present invention, preferably 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4 -One, 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one The concentration of one or more selected from the group of -bonded-saponin can be analyzed, for example, by high performance liquid chromatography analysis using a reverse phase column of a silica-based filler chemically bonded with octyl groups. It can also be confirmed by thin layer chromatography (silica gel, developing phase: chloroform-methanol (9: 1), color developing solution: sulfuric acid).

  The mechanism of melanin production is estimated as follows. L-tyrosine is converted into dopaquinone via L-dopa by the action of tyrosinase, which is oxidatively polymerized enzymatically or non-enzymatically to produce melanin. Therefore, it is considered that melanin production can be suppressed by inhibiting or suppressing the action of tyrosinase. From the above, the melanin production inhibitory effect of the melanin production inhibitor of the present invention can be measured using tyrosinase inhibitory activity as an index, and the inhibitory activity has an activity that can suppress the production of melanin. However, it is preferably 10% or more, more preferably 40% or more, and still more preferably 60% or more.

In the present invention, tyrosinase inhibitory activity can be measured as follows.
(I) An L-tyrosine solution and a phosphate buffer are mixed, a sample solution or water is added thereto, and the absorbance at 470 nm is immediately measured;
(Ii) Incubate the mixed solution of step (i) at 37 ° C. for 10 minutes, add a tyrosinase solution and stir, then allow the enzyme reaction at 37 ° C. for 15 minutes, and then measure the absorbance at 470 nm;
(Iii) Calculate tyrosinase inhibitory activity using the following formula:
Tyrosinase inhibitory activity (%) = {(ba)-(BA) / (ba)} × 100
A: Absorbance in step (i) when using sample solution B: Absorbance in step (ii) when using sample solution a: Absorbance in step (i) when using water b: Using water Absorbance in step (ii)

In addition, the melanin production inhibitory effect of the melanin production inhibitor of the present invention is that the B-16 melanoma cells are cultured at 37 ° C. for 7 days in a fetal bovine serum-added Eagle's MEM medium to which the inhibitor is added. It can be evaluated by using the degree of whitening of the cells obtained by centrifugation as an index.
(Evaluation criteria)
High degree of whitening: Almost whitened, no brown cells seen Whiteness degree: Somewhat whitened, no brown cells seen Whiteness: Low whitened

  The melanin production inhibitor of the present invention can be used as a cosmetic product that prevents white spots and freckles due to the deposition of melanin pigments and has a whitening effect.

  The content of the melanin production inhibitor in the cosmetic of the present invention is preferably 0.01 to 10% by weight, more preferably 0.1 to 5% by weight as a solid content from the viewpoint of a better whitening effect and cost performance. It is.

  In the cosmetic of the present invention, in addition to the melanin production inhibitor, ingredients conventionally used in cosmetics such as ascorbic acid, ascorbic acid glucoside, arbutin, taxide, 3,4-dimethoxyphenyl-OD-glucose , Hydroquinone, l-cysteine, mulberry extract, licorice extract and other substances having a whitening effect may be contained.

  Examples of the cosmetics of the present invention include cosmetics such as lotions, emulsions, cleansing creams, massage creams, makeup cosmetics such as packs and foundations, soaps, facial creams, body lotions, body shampoos and the like. These cosmetics are prepared in the same manner as normal cosmetics except that the melanin production inhibitor is added.

  Next, although an Example demonstrates this invention concretely, this invention is not limited only to the said Example.

Example 1 Preparation 1 of Melanin Production Inhibitor
Molasses (160 g) was dissolved in 4 L of water, filtered to remove impurities, and a molasses aqueous solution was obtained. This was passed through an Amberlite XAD-2 column, washed with water and then eluted with 25 wt% MeOH.

  The obtained 25 wt% MeOH fraction (5.17 g) was partitioned with n-BuOH and water to obtain a BuOH layer (1.13 g), BuOH was distilled off, and the fraction was collected on a TOYOPEARL HW-40C column ( And eluting with 10% MeOH at 25 × 65 cm), detecting the elution peak at an absorbance of 270 nm, and fractionating into 6 fractions for each main peak component, respectively, fraction 1 (30 mg), fraction 2 (144 mg), fraction 3 (437 mg), fraction 4 (124 mg), fraction 5 (118 mg), and fraction 6 (131 mg) were obtained.

  Among these, fraction 4, which showed the strongest tyrosinase inhibitory activity, was eluted with 15 wt% MeOH using a low pressure preparative column (LiChroprep RP-8), and the elution peak was detected at an absorbance of 270 nm. Each fraction was fractionated into three fractions to obtain solid contents of fraction 4-1 (5.1 mg), fraction 4-2 (2.3 mg), and fraction 4-3 (7.1 mg), respectively. . These fractions 4-1 to 4-3 were confirmed to have tyrosinase inhibitory activity.

These fractions were subjected to IR measurement (Fourier transform infrared spectrophotometer FTS-3000, Bio-Rad). EI-MS (70 eV) was measured with a double convergence mass spectrometer M-2500 (Hitachi). ¹ H-NMR, ¹³ C-NMR and two-dimensional NMR were measured at room temperature using a nuclear magnetic resonance absorber JNM-A500 (JEOL) using deuterated methanol (CD ₃ OD) or deuterated chloroform (CDCl ₃ ) as a solvent.

  As a result, it was found that the component of fraction 4-2 was 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one. In addition, fraction 4-1 was found to be taxoxide. Fraction 4-3 was further purified by preparative HPLC (Develosil ODS-MG-5; 8.0 × 250 mm) and analyzed to find guaiacylglycerol-β-D-glucopyranoside and syringylglycerol-β-D- It was glucopyranoside.

Example 2 Preparation 2 of Melanin Production Inhibitor
Molasses (250 g) was dissolved in 7 L of water and filtered to remove impurities to obtain a molasses aqueous solution. This was passed through an Amberlite XAD-2 column, washed with water and then eluted with 25 wt% MeOH. This 25 wt% MeOH elution fraction (8.5 g) was passed through a Preparative C18 column (1 × 35 cm, ODS column, manufactured by Waters) and eluted with 5% MeOH (2.6 g). Got. This was eluted with a TOYOPEARL HW-40C column (25 × 65 cm) using 10% MeOH, an elution peak was detected at an absorbance of 270 nm, and each main peak component was fractionated into 5 fractions. 1 (141 mg), fraction 2 (629 mg), fraction 3 (936 mg), fraction 4 (274 mg), fraction 5 (392 mg) were obtained.

  Among these, fraction 4, which showed the strongest tyrosinase inhibitory activity, was eluted with 15 wt% MeOH using a low pressure preparative column (LiChroprep RP-8), and the elution peak was detected at an absorbance of 270 nm. Each fraction was fractionated into three fractions to obtain solid fractions of fraction 4-1 (7.1 mg), fraction 4-2 (4.3 mg), and fraction 4-3 (12.3 mg), respectively. . These fractions 4-1 to 4-3 were confirmed to have tyrosinase inhibitory activity.

These fractions were subjected to IR measurement (Fourier transform infrared spectrophotometer FTS-3000, Bio-Rad). EI-MS (70 eV) was measured with a double convergence mass spectrometer M-2500 (Hitachi). ¹ H-NMR, ¹³ C-NMR and two-dimensional NMR were measured at room temperature using a nuclear magnetic resonance absorber JNM-A500 (JEOL) using deuterated methanol (CD ₃ OD) or deuterated chloroform (CDCl ₃ ) as a solvent. As a result, it was found that the component of fraction 4-2 was 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one. In addition, fraction 4-1 was found to be taxoxide. Fraction 4-3 was further purified by preparative HPLC (Develosil ODS-MG-5; 8.0 × 250 mm) and analyzed to find guaiacylglycerol-β-D-glucopyranoside and syringylglycerol-β-D- It was glucopyranoside.

Example 3
As a soybean, 100 g of tin yutaka was pulverized, 1000 ml of 70% ethanol aqueous solution was added, and the mixture was extracted at room temperature for 7 hours. Then, it filtered and concentrated the filtrate at 40 degrees C or less. To this concentrate, 100 ml of water and 100 ml of butanol were added and dissolved to obtain a butanol layer. The butanol layer was concentrated under reduced pressure to obtain 50 mg of concentrate. These are produced by soybean DDMP saponin (2,3-dihydro-2) according to an existing method of HPLC analysis using an ODS column (Biosci. Biotech. Biochem., Vol. 57, No. 4, 546-550, 1993). , 5-dihydroxy-6-methyl-4H-pyran-4-one-linked-saponin).

Example 4
The tin yutaka was treated in exactly the same manner as in Example 3 to obtain about 52 mg of soybean DDMP saponin. This was dispersed and dissolved in 10 ml of water and allowed to act on β-glucosidase, and then 10 ml of butanol was added and stirred well to obtain an aqueous layer. The aqueous phase was concentrated to obtain 5 mg of the concentrate. This concentrate was subjected to IR measurement (Fourier transform infrared spectrophotometer FTS-3000, Bio-Rad). EI-MS (70 eV) was measured with a double convergence mass spectrometer M-2500 (Hitachi). ¹ H-NMR, ¹³ C-NMR and two-dimensional NMR were measured at room temperature using a nuclear magnetic resonance absorber JNM-A500 (JEOL) using deuterated methanol (CD ₃ OD) or deuterated chloroform (CDCl ₃ ) as a solvent. As a result, the concentrate was found to be 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one.

Test Example 1 Measurement of Tyrosinase Inhibitory Activity 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one obtained in Examples 1 and 2 and soybean DDMP obtained in Example 3 Saponin (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one-linked-saponin) and 2,3-dihydro-2,5-dihydroxy- obtained in Example 4 6-Methyl-4H-pyran-4-one, and arbutin, kojic acid and 3-hydroxy-4-pyranone dissolved in a concentration of 0.3 mg / ml and 0.5 mg / ml, respectively (0. 05 mM, pH 6.8) To 50 μL, 0.5 mg / ml L-tyrosine solution 150 μL and phosphate buffer 750 μL were added, and the absorbance at 470 nm was immediately measured.

  Next, the mixed solution was preincubated at 37 ° C. for 10 minutes, and then 25 μl of tyrosinase solution (from mushrooms, 470 units) was added and stirred, followed by enzyme reaction at 37 ° C. for 15 minutes, and then the absorbance at 470 nm was measured.

  Based on the absorbance at 470 nm obtained above, the tyrosinase inhibitory activity of each compound was measured. The results are shown in Table 1.

  From the results in Table 1, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one obtained in Examples 1 and 2 and soybean DDMP saponin obtained in Example 3 ( 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one-linked-saponin) and 2,3-dihydro-2,5-dihydroxy-6- obtained in Example 4 It can be seen that methyl-4H-pyran-4-one has tyrosinase inhibitory activity at a lower concentration than the conventionally known arbutin, kojic acid, and 3-hydroxy-4-pyranone.

Test Example 2 Melanin Production Inhibitory Effect Test Using Cultured Cells 2 × 10 ⁵ B16 melanoma cells were tested in a test dish (2,3-dihydro-2,5-dihydroxy-6-methyl-4H- 10% fetal bovine serum-added Eagle MEM supplemented with 0.05% by weight of pyran-4-one, soybean DDMP saponin, 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one) The medium was used and cultured for 7 days at 37 ° C. in air containing 5% carbon dioxide gas.

After completion of the culture, Dulbecco's phosphate buffer containing 0.025 wt% trypsin was added to the culture dish to detach the cells, and the number of cells was counted. The cells obtained by centrifugation were observed with the naked eye, and the degree of whitening of the cells was evaluated according to the following evaluation criteria.
(Evaluation criteria)
High degree of whitening: Almost whitened, no brown cells seen Whiteness degree: Somewhat whitened, no brown cells seen Whiteness: Low whitened

In the case of the control to which no melanin production inhibitor was added, the number of cells after 7 days of culture was 5.4 × 10 ⁵ and the degree of whitening was small.

In the case of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, the number of cells after 7 days of culture was 4.8 × 10 ⁵ and the degree of whitening was large.

In the case of soybean DDMP saponin, the number of cells after 7 days of cultivation was 5.0 × 10 ⁵ cells and the degree of whitening was medium.

In the case of 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one, the number of cells after 7 days of culture was 4.7 × 10 ⁵ and the degree of whitening was large.

  From the above results, when melanoma cells were cultured with the addition of the melanin production inhibitor of the present invention, the degree of whitening was large and the toxicity to the cells was hardly recognized. Therefore, it is considered that the melanin production inhibitor of the present invention is hardly toxic to the human body.

Example 5 Cosmetics Containing Melanin Formation Inhibitor 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one or 2,3-dihydro-2,5-dihydroxy- of the present invention Cosmetics containing 6-methyl-4H-pyran-4-one or 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one-linked-saponin (soybean DDMP saponin) A prescription example is shown. In addition, a compounding quantity is weight%.
(Formulation 1: lotion)
Glycerin 3.0
Propylene glycol 2.0
Oleyl alcohol 0.1
Polyoxyethylene (20) sorbitan monolaurate 1.5
Ethanol 20
2,3-dihydro-3,5-dihydroxy-6-methyl-
4H-pyran-4-one 0.3
Perfume and preservatives Suitable amount Purified water Total 100

(Formulation 2: Cream)
Squalane 5.0
Stearic acid 2.0
Stearyl alcohol 7.0
Reduced lanolin 2.0
Octyldodecanol 6.0
Polyoxyethylene (25) cetyl alcohol 3.0
Lipophilic glyceryl monostearate 2.0
Propylene glycol 5.0
Soybean DDMP saponin 0.01
Perfume and preservatives Suitable amount Purified water Total 100

(Formulation 3: Latex)
Liquid paraffin 10.0
Stearic acid 0.2
Cetanol 1.5
Vaseline 3.0
Lanolin alcohol 2.0
Polyoxyethylene (10) monooleate 2.0
Glycerin 3.0
Propylene glycol 5.0
Triethanolamine 1.0
2,3-dihydro-2,5-dihydroxy-
6-Methyl-4H-pyran-4-one 0.1
Perfume and preservatives Suitable amount Purified water Total 100

(Formulation 4: Pack)
Polyvinyl alcohol 15.0
Sodium carboxymethylcellulose 5.0
Propylene glycol 3.0
Ethanol 10.0
2,3-dihydro-3,5-dihydroxy-
6-Methyl-4H-pyran-4-one 1.0
Perfume and preservatives Suitable amount Purified water Total 100

Test example 3
40 subjects who are suffering from darkness, stains, and freckles are used as a panel, and the half of 20 subjects are from Formula 5 of Example 5 described above, and the other 20 subjects are from Formula 1 of Example 3 of lotion. The whitening effect was determined when a lotion (comparative example) with a formulation excluding 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one was used every day for 3 months. As a result, when Formulation 1 of Example 3 was used, lotion was effective (pigmentation was considerably thinned): 10 people, somewhat effective (pigmentation was slightly thinned): 7 people, ineffective (pigmentation) There was no change in deposition): 3 people. In addition, when the skin lotion of the comparative example was used, effective (pigmentation was considerably thinned): 0 people, slightly effective (pigmentation was slightly thinned): 5 people, ineffective (pigmentation did not change) E): 15 people. As can be seen from the results, the whitening effect was clearly observed in the lotion containing the product of the present invention, compared with the lotion to be compared.

  The melanin production inhibitor of the present invention can be used for cosmetics having a whitening effect.

Claims (3)

The melanin production inhibitor by the tyrosinase inhibitory effect which uses as an active ingredient 1 type, or 2 or more types chosen from the group represented by the following general formula and soybean DDMP saponin.

However, in formula, R1 shows a hydrogen atom (H) or a hydroxyl group (OH). R2 represents a hydrogen atom (H) or a hydroxyl group (OH).   Of 2,3 dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 2,3 dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one and soy DDMP saponin The melanin production inhibitor by the tyrosinase inhibitory effect which uses 1 type, or 2 or more types chosen from a group as an active ingredient.   A cosmetic comprising the melanin production inhibitor according to claim 1 or 2.