JP2009173584A - Silybin glycoside-containing external composition for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To develop an external composition for skin etc., obtained by formulating silybin glycoside. <P>SOLUTION: The external composition for the skin contains the silybin glycoside. The external composition for the skin, a wrinkle formation inhibitor, a differentiation inhibitor of epidermal cornification cells, an external composition for the skin for preventing aging, a production inhibitor of type I collagen, and an improver of rough skin caused by sunburn, having the mechanism of action of the silybin improved by using the silybin glycoside having high solubility can also be provided. Especially, the composition has high water solubility, and safeness, low irritation, and range of use is improved by the composition. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an external composition for skin.

  Silymarin, which contains silybin as the main component, is useful for preventing skin aging, promotes healing in the treatment of erythema, burns, dystrophic conditions of the skin or mucous membrane, dermatitis, etc., and stimulates from the external environment (radiation, It is known to be useful for protecting the skin from wind, sun, etc. (see Patent Document 1: Japanese Patent Laid-Open No. 1-100132). Further, silybin inhibits differentiation of epidermal keratinocytes (Patent Document 2: see JP-A-2004-91397), silymarin containing silybin as a main component, promotes type I collagen production (Patent Document 3: WO 2004/85429). No. gazette) is known.

On the other hand, since silybin is hardly dissolved in water and oil, it has a problem that it is difficult to mix it with an aqueous composition, and a drink technology in which silymarin is dispersed (Patent Document 4: JP-A-2002-2002). 34505), technology that makes biocompatibility advantageous by using silymarin as a phospholipid complex (see Patent Document 1: Japanese Patent Laid-Open No. 1-100132), and technology that improves bioavailability by using a microemulsion composition. (Patent Document 5: refer to Japanese Patent Publication No. 2003-503441), and a technique for producing an encapsulated complex of silybin using a cyclodextrin derivative (Patent Document 6: refer to Japanese Patent Laid-Open No. 3-206090) is disclosed.
However, even if these techniques are used, the precipitation of silybin may not always be sufficiently suppressed, and even if the precipitation of silybin can be suppressed, there are restrictions on the prescription design.

  It is known that glucose glycosides, galactose glycosides, lactose glycosides, and maltose glycosides of silybin have an antioxidant action and are superior in water solubility compared to silybin (Non-patent Document 1: Kosina P. et al., Phytother. Res. 16, S33-S39 (2002)), composition for external use of skin containing silybin glycoside, wrinkle formation inhibitory effect of silybin glycoside, inhibition of epidermal keratinocyte differentiation There is no known effect or type I collagen production promoting effect.

Japanese Patent Laid-Open No. 1-100132 JP 2004-91397 A WO2004 / 85429 JP 2002-34505 A Special table 2003-503441 gazette JP-A-3-206090 Kosina P. et al., Phytother. Res. 16, S33-S39 (2002)

  This invention makes it a subject to develop the composition for external use of skin etc. which use silybin glycoside as an active ingredient.

The present inventors have completed the present invention by using silybin glycoside.
That is, the main configuration of the present invention is as follows.

(1) A composition for external use on skin containing silybin glycoside.
(2) The external composition for skin according to (1), wherein the silybin glycoside is silybin lactoside of formula (1) or silybin maltoside of formula (2).
Formula (1)
Formula (2)

(3) A wrinkle formation inhibitor comprising silybin glycoside as an active ingredient.
(4) An epidermal keratinocyte differentiation inhibitor comprising silybin glycoside as an active ingredient.
(5) A type I collagen production promoter comprising silybin glycoside as an active ingredient.
(6) An agent for improving rough skin caused by sunburn, comprising silybin glycoside as an active ingredient.
(7) The agent according to any one of (3) to (6), wherein the silybin glycoside is silybin lactoside of formula (1) or silybin maltoside of formula (2).
Formula (1)
Formula (2)

(8) The external composition for skin according to (2) or the agent according to (7), wherein 0.008 to 5.0% by weight of silybin glycoside is contained using water as a solvent.

1. The composition for external use of skin with improved action mechanism of silybin by using highly soluble silybin glycoside, wrinkle formation inhibitor, epidermal keratinocyte differentiation inhibitor, composition for external application of skin to prevent aging, type I It has become possible to provide a collagen production promoter and an agent for improving rough skin caused by sunburn. In particular, water solubility is high, and safety, hypoallergenicity, and use range are improved.
2. In particular, as the silybin glycoside, silybin lactoside represented by chemical formula (1) or silybin maltoside represented by chemical formula (2) is effective.
3. The silybin glycoside used in the present invention has high water solubility and can be used as an aqueous solution type dosage form. Skin preparations such as lotions, emulsions, creams, packs, makeup base lotions, makeup creams, makeup skin preparations such as emulsions or creamy foundations, bodies such as hand creams, leg creams, body lotions Skin external composition, bathing agent, and the like.
4). The silybin glycoside used in the present invention can dissolve 0.0008 to 5.0% by weight in water. Even an emulsion can be highly blended in the aqueous part.

Silybin (CAS No. 22888-70-6) is a flavono extracted from the Asteraceae Maria Thistle (scientific name Silibam marianam Gaertn, also known as thistle, giant thistle, milk thistle; CAS No. 84604-20-6). It is a kind of lignan. Flavonolignans extracted from Maria thistle are collectively called Silymarin (CAS No. 65666-07-1), and in addition to Silybin, Silydianin (CAS No. 29782-68-1), Silychristin (Silichristin). CAS No. 33889-69-9), isosilybin (CAS No. 72581-71-6) and the like.
Silybin can be isolated from silymarin using chromatography, and a reagent can be purchased and obtained.

According to the literature (Kren V. et al., J. Chem. Soc., Perkin Trans 1,2467-2474 (1997)), silybin glycoside is a sugar whose hydroxyl group is protected by silybin with an acetyl group using Lewis acid as a catalyst. And can be prepared by deacetylation. In this reaction system, a sugar is selectively glycosidic bonded to the hydroxyl group of the primary alcohol of silymarin.
Silybin is reacted with peracetyl lactose using a Lewis acid as a catalyst to form a glycoside bond and deacetylated to obtain silybin lactoside of formula (1).
Formula (1)

Silybin is reacted with peracetyl maltose using Lewis acid as a catalyst to form a glycosidic bond and deacetylated to obtain silybin maltoside of formula (2).
Formula (2)

  The silybin glycoside used in the present invention is excellent in water solubility, and silybin lactoside and silybin maltoside can be dissolved in about 5% in water. Therefore, if it is a silybin glycoside, it can be blended with a lotion for which silybin could not be blended.

  The composition for external use of the skin of the present invention includes an oil agent, a surfactant, a preservative, a polyhydric alcohol, ethanol, a saccharide, a sequestering agent, a water-soluble polymer, and the like within a range not impairing the effects of the present invention. Polymers, thickeners, powder components, UV absorbers, UV blockers, humectants, fragrances, pH adjusters, and the like can be included. In addition, vitamins, skin activators, blood circulation promoters, resident bacteria control agents, active oxygen scavengers, anti-inflammatory agents, whitening agents, bactericides, and other medicinal components and physiologically active components can also be contained.

In the present invention, the silybin glycoside used in the present invention is excellent in water solubility, and silybin lactoside and silybin maltoside can be dissolved in water by about 5%. Therefore, the silybin glycoside can also be blended with lotions that have been difficult to blend with silybin.
Examples of the wrinkle formation inhibitor comprising the silybin glycoside of the present invention as an active ingredient include skin external compositions for improving wrinkles such as lotions, emulsions, creams and packs, quasi drugs for improving wrinkles, and wrinkle improving drugs. Is mentioned. Even in the case of an emulsion, silybin glycoside can be blended at a high concentration in the aqueous part.

The epidermal keratinocyte differentiation inhibitor comprising the silybin glycoside of the present invention as an active ingredient suppresses differentiation of epidermal keratinocytes, maintains proliferation, prevents, prevents, and improves turnover delay, aging It prevents skin flattening caused by UV irradiation and regenerates aging skin, so that it can be used as an anti-aging skin external composition.
The type I collagen production promoter comprising the silybin glycoside of the present invention as an active ingredient can be expected to improve skin elasticity and elasticity and prevent, prevent and improve wrinkles and sagging. It can be used as a composition for external use on the skin.

(Synthesis of silybin lactoside)
Silybin lactoside was synthesized according to the method of Helferich.
Trifluoride of silybin (3.0 g, 6.2 mol) and octa-O-acetyl-D-lactose (6.3 g, 9.2 mol) in 180 ml of dichloromethane-acetonitrile (1: 1, v / v) Boron dimethyl ether complex (1.14 ml, 12.4 mmol) was stirred at room temperature for 19 hours in the presence of nitrogen. After completion of the reaction, a saturated aqueous sodium hydrogen carbonate solution was added while cooling with ice, and the mixture was extracted twice with 150 ml of dichloromethane. After the anhydrous sodium sulfate treatment, the extraction solvent was removed with an evaporator.
After reacting triethylamine-methanol-water (1: 8: 1) at 35 ° C. for 30 hours, the solvent was removed by an evaporator. Purification was performed using BONDESIL-C18 (Varian) to obtain silybinlactoside (1.0 g, yield 20%). The resulting silica bottle lactoside was confirmed by MS spectrum, [M + H] ^+: was detected 807.5 peak of.

(Synthesis of silybin maltoside)
Silybin maltoside was synthesized according to the method of Helferich.
Trifluoride solution of silybin (3.0 g, 6.2 mol) and octa-O-acetyl-D-maltose (6.3 g, 9.2 mol) in 180 ml of dichloromethane-acetonitrile (1: 1, v / v) Elementary dimethyl ether complex (1.14 ml, 12.4 mmol) was stirred and reacted at room temperature for 19 hours in the presence of nitrogen. After completion of the reaction, a saturated aqueous sodium hydrogen carbonate solution was added while cooling with ice, and the mixture was extracted twice with 150 ml of dichloromethane. After the anhydrous sodium sulfate treatment, the extraction solvent was removed with an evaporator.
After reacting triethylamine-methanol-water (1: 8: 1) at 35 ° C. for 30 hours, the solvent was removed by an evaporator. Purification was performed using BONDESIL-C18 (Varian) to obtain silybin maltoside (1.0 g, yield 20%). The resulting silica bottle lactoside was confirmed by MS spectrum, [M + H] ^+: was detected 807.5 peak of.

Water solubility test Experimental method Silybin, silybin lactoside, and silybin maltoside (hereinafter, silybin is sometimes referred to as SB, silybin lactoside as SBL, and silybin maltoside is sometimes referred to as SBM) are weighed in a 1.5 ml tube, and purified water is added thereto. In addition to each concentration, it was visually determined whether the appearance was transparent, and whether it was precipitated as a precipitate when centrifuged at room temperature (15000 rpm, 5 min). For SB, because it is very poor in water solubility, weigh a small amount in a beaker, add water, stir with a stirrer for about 1 hour, stop mixing operation and determine that no precipitate is found after 1 hour. did.

  As a result of the experiment, both SBL and SBM showed a dramatic improvement in water solubility as compared with SB, and the water solubility was improved about 5000 times or more. The superiority or inferiority of solubility between SBL and SBM could not be detected. An SB concentration of 0.01 mM corresponds to 0.0005% (w / v). SBL and SBM concentrations of 50 mM and 60 mM correspond to 4.1% (w / v) and 4.9% (w / v), respectively. Therefore, when the solubility of SB, SBL, and SBM is compared in terms of mass / volume%, the solubility of SBL and SBM is improved by about 10,000 times compared to SB. In the case of SB, it was difficult to contain water-soluble type skin external composition and the like in SB, but in SBL, it was contained at a concentration of 4.1% (w / v). In SBM, it can be contained at a concentration of 5.0% (w / v). Note that the concentration of SBL and SBM of 0.01 mM corresponds to 0.0008% (w / v).

Epidermal keratinocyte differentiation inhibition test / proliferation maintenance action Experimental material
1.1 Human Normal Epidermal Keratinocytes Human normal epidermal keratinocytes NHEK (Asahi Techno Glass) were cultured in a 37 ° C.-5% CO ₂ incubator in the epidermal keratinocyte medium: KGM (Asahi Techno Glass). In this experiment, cells having 3 to 5 generations were used.
1.2 KGM (Medium for epidermal keratinocytes)
KGM is the epidermal keratinocyte basal medium with human epidermal growth factor (0.1 ng / ml), insulin (5.0 μg / ml), hydrocortisone (0.5 μg / ml), gentamicin (50 μg / ml), amphotericin B (50 μg / ml). ml) and bovine pituitary extract (2 ml). When samples such as silybin glycosides were added to cells, experiments were conducted using KGM medium except for bovine pituitary extract.
1.3 Addition Sample Silybin (SB), silybin maltoside (SBM), and silybin lactoside (SBL) were dissolved in DMSO (dimethylsulfoxide: Wako Pure Chemical Industries, Ltd.) and added at various concentrations.

2. experimental method
2.1 Epidermal keratinocyte differentiation inhibition test
NHEK was suspended at 5 × 10 ⁴ / ml with KGM, seeded in a 6-well plate at 4 ml / well, cultured for 24 hours, and the cells were allowed to adhere to the plate. KGM excluding bovine pituitary extract to which each compound was added was treated with 4 ml / well and cultured for 8 to 10 days while changing the medium every 2 days. Morphological observation was performed with a microscope every day, and when the DMSO-treated control cells showed differentiation-like morphological changes (flattening), photographs were taken and the culture was terminated.
2.2 Epidermal keratinocyte proliferation maintenance test The cells obtained in the above experiment were detached from the plate by trypsin treatment, and then suspended in KGM to 2.5 × 10 ⁴ / ml. The cell suspension was seeded in a 24-well plate at 2 ml / well, and cultured for 8 days while changing the medium every 2 days. After culturing, NHEK was removed from the plate by trypsin treatment, and the number of cells was measured with a Cole counter (Beckman Coulter).
3. 3. Experimental results 3.1 Epidermal keratinocyte differentiation inhibition test The experimental results obtained are shown in FIG. This figure is a micrograph of the cells.
In the control group treated with DMSO, Control and SB 3 μM (cultured in a medium supplemented with 3 μM silybin), the epidermal keratinocytes were flattened and showed differentiation-like morphological changes. In contrast, differentiation-like morphology was not observed in SBM 3 μM and SBL 3 μM. When cultured in a medium supplemented with 10 μM each of SB, SBL, and SBM, all differentiation of epidermal keratinocytes was suppressed. SB, SBL, and SBM have an inhibitory action on differentiation of epidermal keratinocytes, but SBM and SBL have an excellent inhibitory effect on differentiation of epidermal keratinocytes compared with SB.

3.2 Epidermal keratinocyte proliferation maintenance test In the above-mentioned epidermal keratinocyte differentiation inhibition test, if differentiation is suppressed, the cells should maintain their proliferative ability and proliferate sequentially by subculture. Differentiated cells cannot proliferate because differentiation is an additive reverse reaction.
Therefore, the cells obtained in the above test were passaged, and the number of the proliferated cells was examined by measuring the number of proliferated cells.

  The result is shown in FIG. At the sample concentration of 3 μM, the cell proliferation capacity is hardly maintained for those with SB added, but the number of cells is increased by 1.8 times compared to the case where no sample is added to SBM and 1.4 times compared to the case where no sample is added. In addition, the effect of maintaining the cell proliferation ability was observed. At a sample concentration of 10 μM, the number of cells increases for SB, SBM, and SBL. SB is 1.5 times that of no sample, SBM is 2.1 times that of no sample, and SBL is 1.8 times that of no sample. The number of cells increased, and the effect of maintaining cell proliferation ability was observed. It can be seen that the effect of maintaining the cell proliferation ability of SBM and SBL is higher than that of SB.

Type I collagen production promoting action Experimental Material 1.1 Human skin fibroblasts Human skin fibroblasts CCD1074SK (Dainippon Sumitomo Pharma Co., Ltd.) were cultured in D-MEM in a 37 ° C-5% CO ₂ incubator. In this experiment, cells with 10 to 15 generations were used.
1.2 D-MEM
D-MEM was used by adding 10% fetal bovine serum (Hyclone) to D-MEM basal medium (GIBCO). When processing the samples, experiments were performed using D-MEM without fetal bovine serum.
2. Experimental method Human skin fibroblasts CCD1074SK were suspended in D-MEM medium containing 10% fetal bovine serum to 3 × 10 ⁵ / ml, seeded in 1 ml in a 10 cm dish, cultured for 24 hours, and the cells were plated. Glued. Each sample in which the medium was dissolved in DMSO was replaced with a D-MEM medium containing no fetal calf serum added at various concentrations. The cell culture solution was collected 48 hours after the medium was changed, and the culture solution was concentrated using an ultrafiltration device. After concentration to about 500 ml or less, protein quantification was performed, and after the amount of protein was aligned, it was used for Western blotting as a cell culture solution concentrated sample.
10 μg of protein was applied per lane, separated by SDS-PAGE, and transferred to a nitrocellulose membrane. The nitrocellulose membrane after transfer was immersed in a blocking solution (a solution in which skim milk was dissolved in PBS containing 0.1% polyoxyethylene (20) sorbitan monolaurate so as to have a concentration of 5%) and blocked at 4 ° C. overnight. . After washing with a washing solution {PBS containing 0.1% polyoxyethylene (20) sorbitan monolaurate}, soaked in a primary antibody {polyclonal antibody against type I collagen (Rockland) prepared to 500 ng / ml with washing solution} at room temperature The reaction was carried out for 1 hour. After washing, it was immersed in a secondary antibody (horseradish peroxidase-labeled anti-rabbit immunoglobulin G prepared to 250 ng / ml with a washing solution) and allowed to react at room temperature for 1 hour. After washing, detection was performed using an ECL plus western plotting detection reagent (Amersham Bioscience).

Experimental Results As a result of the experiments, both SBL and SBM showed a type I collagen production promoting action as in SB. The experimental results are shown in FIG.

  The results of quantifying the intensity of the obtained band using the program software Image J are shown in Table 2, and the comparative production amount when the production amount of type I collagen during DMSO treatment is 1 is shown in FIG.

SB, SBM, and SBL all showed type I collagen production promoting action. Compared to SB, SBM and SBL have a stronger effect of promoting type I collagen production. In particular, when the sample concentration is 10 μM, the effect of SBM and SBL is large, and a remarkable effect at a high concentration is recognized.

Inhibition of moisture transpiration by UV irradiation Inhibition of wrinkle formation Experimental materials and instruments Experimental animal hairless mouse Hos; HR1 週 5 weeks old (Hoshino experimental materials)
1.2 Ultraviolet irradiation device Ultraviolet A wave (FL32SBL / DMR: manufactured by Clinical Supply Co., Ltd.)
Ultraviolet B wave (FL32SE / DMR: manufactured by Clinical Supply Co., Ltd.)
1.3 Transdermal moisture transpiration measuring device
Vapometer (manufactured by Key Science)
1.4 Replica collection instrument and replica analysis system
Reflective replica collection kit and replica analysis system ASA-03RXD manufactured by Asahi Biomed

2. Experimental method 2.1 Rearing environment
The animals were bred in a conventional breeding environment in which food MR and tap water could be freely ingested at 25 ° C. ± 2 ° C., humidity 50% ± 5%.
Each group was divided into 5 groups and reared in the same cage.
The sunshine set day and night every 12 hours from 7am to 7pm.
2.2 Ultraviolet irradiation Irradiation was started after acclimatizing hairless mouse Hos; HR1 for one week. When ultraviolet radiation is transferred to hairless mice in dedicated cages, it was irradiated with ultraviolet rays of UVB20mJ / cm ² and UVA10J / cm ² by one group. Irradiation was carried out for 10 weeks in a three-day cycle of Monday, Wednesday and Friday, and UV irradiation was performed 30 times in total.

2.3 Group setting Within 30 minutes after UV irradiation, 100 μL of SB, SBL, SBM methanol solution or solvent (methanol) was treated on the entire back skin of mice. The concentration of SB, SBL, and SBM coating was set at three points of 1.0%, 0.3%, and 0.1%, respectively, and ultraviolet irradiation was performed on all these groups. About what apply | coated only methanol which is a solvent, the group of ultraviolet non-irradiation and ultraviolet irradiation was provided. The reason why methanol was used as a solvent is to dissolve SB. In methanol, SBM and SBL were completely dissolved even at a concentration of 1%, but only 0.1% of SB was completely dissolved, but 0.3% was slightly precipitated, and 1% was insoluble. Was recognized. Even when insoluble matter was observed in the SB methanol solution, it was used as it was in the experiment.

2.4 Measurement of transcutaneous water transpiration The transcutaneous water transpiration was measured using VapoMeter (manufactured by Keystone Scientific Co., Ltd.) 2 cm from the tail root of the back to the neck and 0.5 cm on the right side from the lumbar spine. The average was obtained by measuring twice. The opening of the measurement terminal used Nail mode (corresponding to a narrow range of mouse skin by narrowing the opening), and each measurement time required about 19 seconds. The measurement date was 10 weeks after UV irradiation.

2.5 Replica Image Analysis Replicas were collected to accurately grasp the formation of wrinkles. The replica image analysis was performed using a reflection replica analysis system ASA-03RXD (manufactured by Asahi Biomed). Using the ASA-03RXD, a shadow image corresponding to the shape of the wrinkles obtained by irradiating the collected replica with parallel light (LED light source) from an angle of 27 degrees is captured by a CCD camera, captured in a computer, and processed. wrinkle volume ratio of the replica surface ^{(μm 3 / mm 2/100} ) was measured by.

2.6 Statistical Analysis The test results were expressed as mean ± standard deviation (SD), and the significance test was performed by Bartlett's test for equivariance. Dunnett's multiple test was performed when the assumption of equal variance was not rejected, and Dunnett's multiple test was performed as reference data when the assumption of equal variance was rejected.

3. Test results 3.1 Body weight fluctuation, appearance observation
After 10 weeks of irradiation, there was no significant difference in body weight changes between the groups. None of the mice showed severe lesions.
As a result of observing the appearance of the mouse skin, wrinkle formation was observed in the UV-treated group treated with methanol in group 2, whereas 0.3% silybin applied group in group 4, all SBM applied groups in groups 6 to 8, and groups The wrinkle-suppressing action was recognized in all the SBL application groups of Group 9 to Group 11.

3.2 Transcutaneous moisture transpiration As a measure of rough skin, VapoMeter was used to measure the moisture transpiration of each group 10 weeks after UV irradiation. The results are shown in Table 3 and FIG.
The transdermal moisture transpiration is higher in the group 2 irradiated with ultraviolet light than in the group 1 unirradiated group. In group 3 to group 11 silybin (SB), silybin glycoside (SBM, SBL) application group,
An increase in transdermal moisture transpiration was significantly suppressed at a risk rate of 1% or less.

  When the water transpiration amount of group 1 (non-ultraviolet irradiation, methanol application) is 0%, and the water transpiration amount of group 2 (ultraviolet irradiation, methanol application) is 100%, groups 3-5 (ultraviolet irradiation, SB 0.1- (1% application) moisture transpiration is 26-76%, groups 6-8 (ultraviolet irradiation, SBM 0.1-1% application) are 11-21%, 9-11 groups (ultraviolet irradiation, SBL0.1) (1% application) was 24 to 27%, and the addition of SB, SBM, and SBL suppressed the increase in moisture transpiration. In particular, the effect of suppressing the increase in the amount of water transpiration of SBM and SBL, which are silybin glycosides, is high. In other words, it has the effect of improving rough skin caused by sunburn.

3.3 Wrinkle volume ratio
After 10 weeks end of irradiation, the formation of wrinkles were taken replica to accurately grasp was measured wrinkle volume ratio of the replica surface ^{(μm 3 / mm 2/100} ) by image analysis. The results are shown in Table 4 and FIG.

  As a result of Dunnett's significant difference test, group 1 (UV-irradiated methanol applied), group 1 (UV-irradiated methanol applied), group 4 (UV-irradiated SB 0.3% applied), group 7 (UV-irradiated SBM0). .3% application) and Group 11 (UV irradiation SBL 1.0% application) each had a significantly reduced wrinkle volume at a risk rate of 5% or less.

[Prescription Example 1 Lotion]
mass%
1. Silybin lactoside 0.3
2. Diglycerin 5.0
3. 1,3-butylene glycol 2.0
4). Dipropylene glycol 3.0
5. Potassium hydroxide appropriate amount 6. Citric acid appropriate amount 7. Purified water residue (production method)
1 to 6 were dissolved in 7.

[Prescription Example 2 Latex]
mass%
1. Silybin maltoside 0.3
2. Hydrogenated soybean phospholipid 0.7
3. Decaglyceryl stearate (HLB12) 2.0
4). Glycerin 8.0
5. Olive oil 8.0
6). Behenyl alcohol 1.0
7). Dipropylene glycol 8.0
8). Carboxyvinyl polymer 0.1
9. Xanthan gum 0.2
10. Potassium hydroxide appropriate amount11. Citric acid appropriate amount 12. Purified water residue (production method)
1 to 4 and 7 to 12 are dissolved by heating at 80 ° C. To this, 5 and 6 heated to about 80 ° C. were added, stirred and mixed with a homomixer, and cooled to 30 ° C. to obtain an emulsion.

[Prescription Example 3 Moisture Serum]
mass%
1. Silybin lactoside 0.2
2. Hydrogenated soybean phospholipid 0.6
3. Decaglyceryl monooleate (HLB12) 1.5
4). Glycerin 7.0
5.1,3-Butylene glycol 5.0
6). Polyethylene glycol 4000 0.1
7). Squalane 5.0
8). Silicone 0.5
9. Lauroyl glutamate di (phytosteryl / octyldodecyl)
0.2
10. Xanthan gum 0.3
11. Potassium hydroxide appropriate amount 12. Citric acid appropriate amount13. Purified water residue (production method)
1 and 11 to 13 are stirred and dissolved, and 4 to 6 and 10 are added, and then heated to about 80 ° C. and dissolved.
To this, 2, 3, 7-9 heated to about 80 ° C. were added and cooled to 30 ° C. to obtain a moisturizing serum.

[Prescription Example 4 Emollient Cream]
mass%
1. Silybin maltoside 0.5
2. Diglycerin 10.0
3. Dipropylene glycol 8.0
4.1,2-Pentanediol 0.5
5. L-serine 0.01
6). Decaglyceryl distearate (HLB 9.5) 0.5
7). Decaglyceryl monomyristate (HLB14) 1.5
8). Olive oil 10.0
9. Macadamia nut oil 1.0
10. Behenyl alcohol 1.5
11. Silicone 2.0
12 Jojoba oil 3.0
13. Tocopherol 0.001
14 SIMULGEL NS (made by SEPPIC) 2.0
15. Xanthan gum 0.1
16. Potassium hydroxide appropriate amount 17. Citric acid appropriate amount 18. Purified water residue (production method)
1 and 16 to 18 are dissolved by stirring, and 2 to 5 are added and dissolved by heating to about 80 ° C. To this, 6 to 14 heated to about 80 ° C. was added and cooled to 30 ° C. to obtain an emollient cream.

[Formulation Example 5 Body Emulsion]
mass%
1. Silybin lactoside 0.2
2. PEG-60 hydrogenated castor oil (HLB14) 1.5
3. Glycerin 9.0
4). Dipropylene glycol 7.0
5. Hyaluronic acid Na 0.001
6). Liquid paraffin 10.0
7). Silicone 3.0
8). Octyldodecanol 4.0
9. (Acrylic acid / alkyl acrylate (C10-30)) copolymer 0.2
10. Potassium hydroxide appropriate amount11. Citric acid appropriate amount 12. Purified water Residual 13. Ethanol 2.5
(Manufacturing method)
1 and 10 to 12 are stirred and dissolved, and 2 to 5 and 9 are added and dissolved by heating to about 80 ° C. To this, 6 to 8 heated to about 80 ° C. was added, cooled to 30 ° C., and 13 was added to obtain an emulsion for the body.

[Prescription Example 6 Massage Cream]
mass%
1. Silybin maltoside 0.05
2. Glycerin 10.0
3. Diglycerin 2.0
4). Propylene glycol 7.0
5. Decaglyceryl monostearate (HLB12) 1.0
6). Cetyl ethylhexanoate 1 2.0
7). Behenyl alcohol 2.0
8). Stearic acid 0.5
9. Sepinob EMT10 (SEPPIC) 0.5
10. Perfume proper amount11. Phenoxyethanol 0.3
12 Potassium hydroxide appropriate amount13. Citric acid appropriate amount14. Purified water residue (production method)
1 and 11 to 14 are stirred and dissolved, and 2 to 4 are added and dissolved by heating to about 80 ° C. To this, 5 to 9 heated to about 80 ° C. was added, cooled to 30 ° C., and 10 was added to obtain a massage cream.

[Prescription Example 7 Emulsification Foundation]
mass%
1. Silybin lactoside 0.1
2. Glycerin 10.0
3. Dipropylene glycol 8.0
4.1,2-Pentanediol 1.0
5. Xanthan gum 0.3
6). Polyglyceryl triisostearate-2 1.0
7). Cyclomethicone 8.0
8). Silicone 5.0
9. Isostearyl neopentanoate 5.0
10. Isostearic acid 1.5
11. Behenyl alcohol 0.5
12 Dextrin palmitate 1.0
13. Talc 3.0
14 Titanium dioxide 5.0
15. Bengala 0.5
16. Yellow iron oxide 1.4
17. Black iron oxide 0.1
18. Potassium hydroxide appropriate amount 19. Citric acid appropriate amount20. Purified water residue (production method)
1 and 18 to 20 are stirred and dissolved, and 2 to 5 are added and dissolved by heating to about 70 ° C. Next, 13-17 well pulverized are added and mixed with stirring. To this, 6-12 heated to about 80 ° C. was added and cooled to 30 ° C. to obtain an emulsified foundation.

The figure which shows an epidermal keratinocyte differentiation suppression test result. The graph which shows an epidermal keratinocyte proliferation maintenance test result. The figure which shows a type I collagen production promotion test result. FIG. 4 is a graph showing the band intensity shown in FIG. The graph which shows the value which measured the amount of water transpiration of the mouse | mouth which performed the ultraviolet irradiation test. The graph which shows the wrinkle volume ratio of the skin replica surface of the mouse | mouth which performed the ultraviolet irradiation test.

Claims (8)

  An external composition for skin containing silybin glycoside. The composition for external use according to claim 1, wherein the silybin glycoside is silybin lactoside of formula (1) or silybin maltoside of formula (2).
Formula (1)

Formula (2) A wrinkle formation inhibitor comprising silybin glycoside as an active ingredient. An epidermal keratinocyte differentiation inhibitor comprising silybin glycoside as an active ingredient. A type I collagen production promoter comprising silybin glycoside as an active ingredient. An agent for improving rough skin caused by sunburn, comprising silybin glycoside as an active ingredient. The agent according to any one of claims 3 to 6, wherein the silybin glycoside is silybin lactoside of formula (1) or silybin maltoside of formula (2).
Formula (1)
Formula (2)   The composition for external use of the skin according to claim 2 or the agent according to claim 7, which contains 0.0008 to 5.0% by weight of silybin glycoside using water as a solvent.