JPH10120546A - Skin whitening preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation high in melanogenesis inhibitory effect, stability and safety, and free from unfavorable color and odor. SOLUTION: This skin whitening preparation is obtained by formulating a base preparation for external use with suitably 0.0001-5.0wt.% or so of a (-)-epicatechin-contg. fraction which is afforded by the following process: a polar solvent extract from at least one kind of plant selected from Polygonum cuspidatum Sieb. et Zucc., Polygonum cuspidatum Sieb. et Zucc. var. hachidyoense Ohwi and Polygonum sachalinense Fr. Schm. is concentrated under reduced pressures, the resultant concentrate is dissolved in 30vol.% ethanol again and then subjected to fractionation by resin column chromatography followed by elution with 40vol.% ethanol, and the resultant fraction is further fractionated by silica gel chromatography.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for skin whitening having an excellent effect of inhibiting melanin production, comprising a fraction obtained by fractionation and purification from a specific plant extract. For more information, see the Japanese knotweed ( Polygonum cuspidatum Sieb.
et Zucc.), Honey beebird ( Polygonum cuspida)
tum Sieb. et Zucc. var. hachidyoense Ohwi), and Ooitadori (Polygonum sachalinense Fr. Schm. Further fractionation of the extract by a polar solvent of one or more plants selected from) image obtained by purification The present invention relates to an external preparation for skin whitening comprising

[0002]

2. Description of the Related Art In the past, skin external preparations for whitening have been of great interest in improving pigmentation symptoms such as skin spots and freckles. Among these, ascorbic acid, cysteine, glutathione, and colloid sulfur And the like have been used as active ingredients. Also, various medicinal plant extracts, flavonoids such as gallic acid, chalcone, and catechins derived from plants, kojic acid, hydroquinone glycosides, and the like are known as whitening agents.

[0003] However, ascorbic acid is easily oxidized and unstable, and cysteine, glutathione and colloidal sulfur have disadvantages such as generation of peculiar off-odor and precipitation. In addition, the medicinal plant extract has problems that the melanin production inhibitory effect is insufficient, that the extract has an undesired color or odor upon use, and that it is difficult to obtain a product of constant quality. Also, regarding kojic acid and the like, it is necessary to consider the maintenance of stability in the preparation, and there is also a substance that may cause side effects due to continuous use.

[0004]

As a means for solving the above-mentioned problems, the inventors of the present invention have proposed a knotweed ( Polygo).
num . cuspidatum Sieb. et Zucc.), Honey beebird ( Polygonum cuspidatum Sieb. et Zucc. var. hach)
idyoense Ohwi) and Giant Knotweed ( Polygonumsachal )
Inense Fr. Schm.) has already disclosed a whitening cosmetic and a tyrosinase biosynthesis inhibitor containing one or more plant extracts selected from JP-A-5-29.
4819, JP-A-8-104646). In the present invention, an object of the present invention is to provide an external preparation for whitening skin which has a high melanin production inhibitory effect, has always stable quality, and has no problems such as color and odor.

[0005]

In order to solve the above problems, fractionation and purification of extracts such as knotweed were attempted.
This time, we succeeded in fractionation of a fraction that has a high melanin production inhibitory effect, and by incorporating it into an external preparation base, it has a high effect of improving pigmentation symptoms and is stable and highly safe. Could be obtained.

That is, in the present invention, the knotweed ( Po
lypidum cuspidatum Sieb. et Zucc.) and the bee housebird ( Polygonum cuspidatum Sieb. et Zucc. var.)
hachidyoense Ohwi) and Giant Knotweed ( Polygonum s)
achalinense Fr. Schm.), an extract of one or more plants selected from polar solvents is concentrated under reduced pressure, redissolved in 30% by volume of ethanol, fractionated by resin column chromatography, and subjected to 40% by volume. Among the fractions obtained by further fractionating the fraction eluted with ethanol by silica gel chromatography, a fraction rich in (-)-epicatechin is contained in a skin external preparation base.

[0007]

The skin whitening preparation for external use according to the present invention exhibits a superior melanin production inhibitory action as compared with the conventional skin whitening preparation, and can always expect a constant and stable melanin generation inhibitory action. Good in safety and safety. Also, no undesired coloring or unpleasant odor is observed.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, an extract as a starting material for fractionation and purification can be obtained using flowers, leaves, stems, roots, and whole plants of knotweeds, and particularly extracted from roots. Are preferred. Examples of the extraction solvent include methanol, ethanol, propanol, isopropanol, butanol, ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, methyl acetate, ethyl acetate, isopropyl acetate, ethyl ether, and isopropyl ether. The use of one or more organic solvents having a high polarity, such as acetone, acetone, or a mixture of these with water
It is preferable from the viewpoint of melanin production inhibitory action. The extraction is performed by cutting or pulverizing the plant as it is or by drying it, and immersing it at a temperature from room temperature to the boiling point of the extraction solvent or lower for about 2 hours to 2 weeks.

[0009] The extract such as knotweed is filtered as necessary, and then concentrated under reduced pressure, and then redissolved in 30% by volume of ethanol. This is fractionated by resin column chromatography. DIAION MCI Gel HP-
20 (manufactured by Mitsubishi Kasei Corporation) can be preferably used. In the resin column chromatography, 40% by volume
The fraction eluted with ethanol is collected and further fractionated by silica gel thin layer chromatography. As a developing solvent at that time, a mixture of chloroform and methanol at a volume ratio of 5: 1 is preferable.

[0010] Of the fractions obtained in the above silica gel thin layer chromatography, CD ₃ OD NMR
The fraction containing the substance identified as (-)-epicatechin has a strong melanin-suppressing action.This fraction is collected and dissolved in a highly polar organic solvent used for extraction or a mixture of these and water. And add to the skin external preparation base. The amount of the fraction in the skin external preparation was 0.0
About 001 to 5.0% by weight is appropriate.

In the present invention, other whitening agents can be added in addition to the fractionation and purification fractions of knotweed and the like. In addition, general external preparations such as oils, humectants, ultraviolet absorbers, fragrances, antioxidants, preservatives, and raw materials for cosmetics can be contained within a range that does not impair the features of the present invention.

The present invention relates to a lotion, an emulsion, a gel,
It can be provided as an external preparation for skin whitening in the form of creams, ointments and the like. Also, skin cosmetics such as lotions, emulsions and creams, makeup base lotions, makeup base creams, makeup cosmetics such as liquid or creamy or ointment type foundations, sunscreen lotions, sunscreen creams, etc. It can also be provided as sunscreen cosmetics, body cosmetics such as hand cream, leg cream, body lotion and the like.

[0013]

EXAMPLES The present invention will be described in more detail with reference to Examples. First, preparation examples of fractionation and purification fractions of knotweed and the like to be contained in the skin whitening external preparation of the present invention are shown below.

Itami ( Polygonum cuspidatum Sieb. E)
t Zucc.) was immersed in 2 l of a 50% by volume aqueous ethanol solution and extracted at room temperature for one week.
The extract was filtered, concentrated under reduced pressure, made 800 ml with a 30% by volume aqueous ethanol solution, and further filtered.
Fractionation was performed using an ON MCI Gel HP-20 (manufactured by Mitsubishi Kasei Corporation) column. The fraction eluted with a 40% by volume aqueous ethanol solution was collected, and further fractionated by silica gel thin layer chromatography using a mixture of chloroform and methanol (volume ratio = 5: 1) as a developing solvent. Among the obtained fractions, the fraction containing (-)-epicatechin was scraped off and dissolved in a 50% by volume aqueous ethanol solution to give a knotweed fraction and a purified fraction.

The action of inhibiting the production of melanin in the above-mentioned knotweed fraction and purified fraction is described below. The melanin production inhibitory effect was evaluated using B16 melanoma cells. First, B
16 melanoma cells were seeded at 1.5 × 10 ⁵ cells per culture dish (diameter 60 mm), and DMEM containing 10 mM fetal calf serum containing 50 mM sodium lactate was used.
Preculture was performed at 37 ° C. for 4 days in 5 ml of medium. Then, as a sample, 5 ml of a 5% by volume fetal bovine serum-containing DMEM medium containing a variety of final concentration of knotweed and purified fractions
The medium was exchanged, and main culture was performed at 37 ° C. for 3 days. At this time, 5% by volume as a control and a negative control
The culture was performed using only the DMEM medium containing fetal calf serum and the DMEM medium containing 5% by volume fetal calf serum containing 40 mM sodium lactate. After completion of the main culture, B16 melanoma cells were separated, the absorbance at 650 nm and 400 nm was measured, and the number of cells was measured at the same time. The inhibition rate of melanin production inhibition of the knotweed fraction and the purified fraction at each concentration was determined by equation (1).

(Equation 1) ( _Where A _650C , A _400C , and N _C are the absorbance and cell number at 650 nm and 400 nm in the control, respectively.
_650S, A _400S, 65 when N _S is that each addition of sample
The absorbance at 0 nm and 400 nm and the number of cells are shown. )

Table 1 shows the melanin production inhibitory effect at each concentration of the knotweed fraction and the purified fraction. In Table 1,
Itadori fraction and purified fraction are about 0.6 μg / ml and about 1
It showed 0% inhibition of melanin production, and the melanin production inhibition rate exceeded 20% with the addition of 40 μg / ml. In addition,
In the negative control, melanin production was almost completely inhibited, but with (-)-epicatechin alone, no significant inhibition of melanin production was observed when added to a final concentration of 40 μg / ml. . Therefore, in the knotweed fraction and the purified fraction, whether the components other than (-)-epicatechin are the main components of the melanin production inhibitory action,
Alternatively, it was considered that melanin production was suppressed by the interaction between (-)-epicatechin and other components.

[Table 1]

Subsequently, the formulation of the skin whitening agent for external use according to the embodiment of the present invention will be described. As the fractions and purified fractions of Itadori and the like, those described above as Preparation Examples were used.

Example 1 Whitening lotion (1) Ethanol 10.0 (wt%) (2) Hydroxyethylcellulose 1.0 (3) Itadori fractionation, purified fraction 0.1 (4) Purified water 88.9 Production method: (1) to (3) are sequentially added to (4) and uniformly mixed and dissolved.

Example 2 Whitening Emulsion (1) Stearic acid 0.2 (% by weight) (2) Cetanol 1.5 (3) Vaseline 3.0 (4) Liquid paraffin 7.0 (5) Polyoxy Ethylene (10E.O.) monooleate 1.5 (6) Tocopherol acetate 5.0 (7) Glycerin 5.0 (8) Methyl parahydroxybenzoate 0.1 (9) Triethanolamine 1.0 (10) Purified water 75.4 (11) Itadori fractionation, purified fraction 0.3 Production method: The oil phase components (1) to (6) are mixed, heated and uniformly dissolved, and kept at 70 ° C. On the other hand, the aqueous phases (7) to (10) are mixed and heated to be uniform, and the temperature is set to 70 ° C. The oil phase component is gradually added to the aqueous phase component while stirring to emulsify, and after cooling, (11) is added and mixed at 40 ° C.

Example 3 Whitening Gel (1) Dipropylene glycol 10.0 (% by weight) (2) Carboxyvinyl polymer 0.5 (3) Potassium hydroxide 0.1 (4) Methyl paraoxybenzoate 0.1 (5) Purified water 88.1 (6) Magnesium ascorbic acid phosphate ester 1.0 (7) Itadori fractionation, purified fraction 0.2 Production method: (2) is uniformly dissolved in (5) After that, (4) was dissolved and added to (1), then (3) was added to increase the viscosity, and (6), (7)
Add and mix.

Example 4 Skin Cream (1) Beeswax 6.0 (% by weight) (2) Cetanol 5.0 (3) Reduced Lanolin 8.0 (4) Squalane 27.5 (5) Glyceryl fatty acid ester 4.0 (6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene (20E.O.) sorbitan 5.0 Monolaurate (8) Propylene glycol 5.0 (9) Methyl paraoxybenzoate 0.1 (10) Purified water 36.9 (11) Itadori fractionation, purified fraction 0.5 Production method: Mix and dissolve the oil phase components of (1) to (7) and heat to 75 ° C. On the other hand, the aqueous phase components (8) to (10) are mixed and dissolved, and heated to 75 ° C. Next, the oil phase component is added to the water phase component and pre-emulsified, and then uniformly emulsified by a homomixer. After cooling, (11) is added and mixed at 40 ° C.

Example 5 Oil-in-water emulsion whitening ointment (1) White petrolatum 25.0 (% by weight) (2) Stearyl alcohol 25.0 (3) Glycerin 12.0 (4) Sodium lauryl sulfate 1. 0 (5) Methyl paraoxybenzoate 0.1 (6) Purified water 35.9 (7) Itadori fractionation, purified fraction 1.0 Production method: Mix and dissolve the oil phase components (1) to (4) And uniform
Heat to 75 ° C. On the other hand, the aqueous phase components (5) and (6) were mixed and dissolved, heated to 75 ° C, and the oil phase component was added thereto to emulsify. After cooling, (7) was added at 40 ° C. Mix.

Example 6 Whitening Lotion (1) Ethanol 10.00 (% by weight) (2) 1,3-butylene glycol 5.00 (3) Itadori fractionation, purified fraction 0.01 (4) Fragrance 0.10 (5) Purified water 84.89 Production method: (1) to (4) are sequentially added to (5), and uniformly mixed and dissolved.

[Example 7] Water-in-oil cream for whitening (1) Liquid paraffin 30.00 (wt%) (2) Microcrystalline wax 2.00 (3) Vaseline 5.00 (4) Diglyceryldiole Ethate 5.00 (5) Sodium L-glutamate 1.60 (6) L-Serine 0.40 (7) Propylene glycol 3.00 (8) Methyl parahydroxybenzoate 0.10 (9) Purified water 52.78 ( 10) Itadori fractionation, purified fraction 0.02 (11) Fragrance 0.10 Production method: (5) and (6) are dissolved in a part of (9) to 50 ° C and 5 ° C.
Add slowly to (4) heated to 0 ° C. with stirring. This was previously mixed and uniformly dispersed in (1) to (3), which were heated and dissolved at 70 ° C., and (7) and (8) were dissolved in the remainder of (9) and heated and dissolved at 70 ° C. Is added with stirring and emulsified with a homomixer. After cooling, at 40 ° C (10), (11)
Is added.

Example 8 Whitening Makeup Base Cream (1) Stearic acid 12.00 (% by weight) (2) Cetanol 2.00 (3) Glyceryl tri-2-ethylhexanoate 2.50 (4) Self-emulsifying glyceryl monostearate 2.00 (5) Propylene glycol 10.00 (6) Potassium hydroxide 0.30 (7) Methyl parahydroxybenzoate 0.10 (8) Purified water 69.45 (9) Titanium dioxide 1.00 (10) Bengala 0.10 (11) Yellow iron oxide 0.40 (12) Fragrance 0.10 (13) Itadori fractionation, purified fraction 0.05 Production method: oils of (1) to (4) The phase components are mixed and heated to 75 ° C. to make uniform. On the other hand, mix the aqueous phase components (5) to (8)
The mixture is heated and dissolved to make the mixture uniform, and the pigments (9) to (11) are added to the mixture and uniformly dispersed by a homomixer. The oil phase component is added to the water phase component, emulsified by a homomixer, cooled, and (12) and (13) are added and mixed at 40 ° C.

[Example 9] Liquid foundation for whitening (1) Stearic acid 2.00 (wt%) (2) Squalane 5.00 (3) Octyldodecyl myristate 5.00 (4) Cetanol 1.00 (5 ) Polyglyceryl monoisopalmitate 9.00 (6) 1,3-butylene glycol 6.00 (7) Potassium hydroxide 0.10 (8) Methyl parahydroxybenzoate 0.10 (9) Purified water 53.66 (10 ) Titanium oxide 9.00 (11) Bengala 7.40 (12) Yellow iron oxide 0.50 (13) Black iron oxide 1.10 (14) Fragrance 0.10 (15) Itadori fractionation and purification fraction 04 Production method: The oil phase components (1) to (5) are mixed and heated to 75 ° C. to make it uniform. On the other hand, the aqueous phase components of (6) to (9) were mixed and
The mixture is heated and dissolved to make the mixture uniform, and the pigments (10) to (13) are added to the mixture and uniformly dispersed by a homomixer. The oil phase component is added to the aqueous phase component, emulsified with a homomixer, cooled, and (14) and (15) are added and mixed at 40 ° C.

Example 10 Sunscreen Emulsion (1) Oleyl Oleate 5.0 (% by weight) (2) Dimethylpolysiloxane 3.0 (3) Vaseline 0.5 (4) Cetanol 1.0 (5 ) Sorbitan sesquioleate 0.8 (6) Polyoxyethylene (20E.O.) oleyl alcohol 1.2 ether (7) 2-Ethylhexyl paramethoxycinnamate 2.0 (8) Oxybenzone 3.0 (9) Dipropylene Glycol 6.0 (10) Hydroxyethylcellulose 0.3 (11) Methyl paraoxybenzoate 0.1 (12) Purified water 73.9 (13) Ethanol 3.0 (14) Fragrance 0.1 (15) Itadori fraction Purified fraction 0.1 Production method: Mix and dissolve oil phase components (1) to (8) to 70 ° C. On the other hand, the aqueous phase components (9) to (12)
° C, and the oil phase component is gradually added to this while stirring to emulsify. After cooling, add (13)-(15) at 40 ° C,
Mix.

Example 11 Whitening Hand Cream (1) Stearic acid 3.00 (% by weight) (2) Glyceryl monostearate 3.00 (3) Cetanol 2.00 (4) Liquid paraffin 6.00 ( 5) Vaseline 3.00 (6) Glycerin 10.00 (7) 1,3-butylene glycol 5.00 (8) Potassium hydroxide 0.25 (9) Methyl parahydroxybenzoate 0.10 (10) Purified water 67 32 (11) Magnesium salt of ascorbic acid phosphate ester 0.25 (12) Itadori fractionation, purified fraction 0.08 Production method: Mix and dissolve the oil phase components (1) to (5) to 75 ° C. I do. On the other hand, the aqueous phase components (6) to (10)
° C, and the oil phase component is gradually added to this while stirring to emulsify. After cooling, add (11) and (12) at 40 ° C,
Mix.

Of the above Examples of the present invention, Examples 1 to 5 were evaluated for the effect of improving pigmentation symptoms. At that time, in each of the examples, the fractionation and purification fractions of the knotweed were replaced with 50% by volume aqueous ethanol solution, and these were designated as Comparative Examples 1 to 5, respectively. The effect of improving the pigmentation symptom was as follows: 20 female panelists with remarkable pigmentation symptoms such as spots and freckles were grouped as one group, and the examples and comparative examples were blinded twice a day for each group for one month. After one month, the state of pigmentation of the skin after one month was observed and compared with that before use. The state of pigmentation was evaluated in accordance with the criteria shown in Table 2, and the average value of 20 persons was calculated and shown in Table 3.

[Table 2]

[0030]

[Table 3] As is clear from Table 3, in the group using the examples of the present invention, a clear improvement in pigmentation symptoms was observed. Especially,
In Example 3, in which the fractionation and purification of Knotweed was combined with magnesium ascorbate phosphate, a synergistic improvement in whitening effect was observed, and in Example 3 where the fractionation and purification of Knotweed were high. Regarding the groups using Example 4 and Example 5, pigmentation was improved to a slight extent in almost all panelists. In contrast, Comparative Example 3
No clear improvement was observed in any of the groups using Comparative Examples other than the above, and the degree of improvement in the pigmentation symptoms was small in the group using Comparative Example 3 as well.

Subsequently, Embodiment 10 and Embodiment 1 of the present invention
1 was used to evaluate the effect of preventing pigmentation. Comparative Examples 10 and 11 were obtained by substituting the fractionated and purified fractions of Knotweed with a 50% by volume aqueous ethanol solution in each Example.
A usage test was conducted by panelists who often work outdoors together with the examples. As panelists, men and women in their 20s and 50s who work outdoors every day were selected,
0 people. Examples and comparative examples were used twice a day by blinds of panelists in each group, and the state of pigmentation of the skin after one month was evaluated according to the criteria shown in Table 2 above, and compared with that before the test was started. The use test was conducted in May when the amount of ultraviolet rays was large. The results are shown in Table 4 by the average value of 20 persons.

[0032]

[Table 4] In Table 4, although some effects of preventing skin pigmentation were observed in the group using the comparative example, in the group using the example of the present invention, pigmentation caused by ultraviolet rays exposed during outdoor work was significantly suppressed. In addition, improvement in pigmentation symptoms was also observed.

In Examples of the present invention, no remarkable coloring or off-flavor is produced at the time of preparation, and even after storage at room temperature for 1 year or more, the appearance change and the prevention of pigmentation symptoms and the reduction of the improvement effect are reduced. Was not found. Further, no adverse effects such as irritation, sensitization and photosensitization on the skin were observed.

[0034]

As described above in detail, the present invention has a high melanin production inhibitory effect, has an effective effect of improving and preventing skin pigmentation, has always stable quality, and has a stable color and odor. It was possible to provide a skin whitening agent for external use without any problem.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Hitoshi Masaki 112-1 Nogami, Okada-cho, Yokaichi, Shiga Prefecture Inside the Noevir Shiga Central Research Laboratory Co., Ltd. (72) Inventor Atsuko Imabori 112-Nogami, Okada-cho, Yokaichi, Shiga 1 Noevir Shiga Central Research Institute, Inc. (72) Inventor Masumi Takei 112-1 Nogami, Okada-cho, Yokaichi-shi, Shiga Pref.

Claims (3)

[Claims] 1. A knotweed ( Polygonum cuspidatum Sieb.
et Zucc.), Honey beebird ( Polygonum cuspida)
tum Sieb. et Zucc. var. hachidyoense Ohwi), and Ooitadori (Polygonum sachalinense Fr. Schm. One or extract with a polar solvent of two or more plants selected from) and concentrated under reduced pressure, re to 30 volume% ethanol After dissolution and fractionation by resin column chromatography, 40
An external preparation for whitening skin, comprising a fraction containing (-)-epicatechin, which is obtained by further fractionating a fraction eluted with a volume% of ethanol by silica gel chromatography. 2. The content of the fraction according to claim 1,
0.0001 to 5.0% by weight,
An external preparation for skin whitening. 3. The skin external preparation according to claim 1, wherein the whitening skin external preparation is a whitening cosmetic.