JP2010229062A - Bleaching agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To develop a new bleaching agent by utilizing melanin production-inhibiting effects of Acer truncatum Bunge for the bleaching agent. <P>SOLUTION: The bleaching agent contains an extract from the Acer truncatum Bunge as an active ingredient. The melanin synthesis inhibitor contains the extract from the Acer truncatum Bunge as an active ingredient. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a whitening agent.

The amount of ultraviolet rays that reach the epidermis tends to increase year by year due to air pollution and the destruction of the ozone layer, and skin troubles such as skin spots, freckles, and darkness due to ultraviolet rays are increasing accordingly. Melanin pigment is produced by ultraviolet rays, and when it is produced in excess, it causes skin problems such as spots, freckles, and darkness. As a method for suppressing the production of this melanin pigment and preventing spots, freckles, and darkness, a skin cosmetic containing a glucose glycoside of kojic acid, L-ascorbic acid and its derivative L-ascorbic acid has been conventionally used. (Patent Document 1: Japanese Patent Application Laid-Open No. 4-184212) has been proposed. However, further development of whitening agents is required.
A moisturizing agent containing a maple plant extract is known (Patent Document 2: JP-A No. 2003-1113068).

JP-A-4-18212 JP 2003-1113068 A

The inventors of the present invention paying attention to Chinese maple maple and have been conducting a research study on its action, and have found an inhibitory effect on melanin production.
It is to develop a new whitening agent.

The main configuration of the present invention is as follows.
(1) A whitening agent characterized by containing an extract from Chinese maple maple as an active ingredient.
(2) A melanin synthesis inhibitor comprising an extract from Chinese maple maple as an active ingredient.
(3) The agent according to (1) or (2), wherein the extract is an extract from leaves of Chinese corn maple.
(4) The agent according to any one of (1) to (3), wherein the extract is a hot water extract or an ethanol extract.
(5) The agent according to any one of (1) to (4), which is an external preparation for skin.
(6) The agent according to any one of (1) to (5), wherein the extract contains 0.0004% by weight or more.

The whitening agent containing the Sinaia maple extract of the present invention can be used as a whitening cosmetic and a quasi-drug for whitening. In particular, since it has a melanin synthesis inhibitory effect caused by ultraviolet exposure, it can be used as a melanin synthesis inhibitor, and is effective in taking measures against sunburn caused by outdoor activities.
In the present invention, an extract obtained from the leaves of Chinese corn maple can be used, so that it can be collected every year without damaging the plant body. Not only fresh leaves but also dead leaves can be used.
The dosage form can be used for oral, parenteral and topical skin applications. In particular, lotions, emulsions, creams, ointments, plasters, haps, aerosols and the like which are external preparations for skin are suitable.
Low cytotoxicity and safe.

The graph which shows a cytotoxic test result. The graph which shows a three-dimensional skin model blackening inhibitory effect. The graph which shows a melanin synthesis suppression result.

Acer truncatum Bunge used in the present invention is a kind of maple native to northern China.
Chinese maple maple is called the Chinese name Yu Bao and is distributed in Northeast China, North China, Henan and Shanxi. Tree height is 8-10m and leaves are 5 pieces. The extract of Sinaia maple is not focused on, and the present inventors have been able to find out during the search for new candidate substances.
In the present invention, leaves of Chinese corn maple can be used. Not only new leaves that have not withered, but also dead leaves can be used. As an extract of the leaves of Chinese corn maple, the leaves or dead leaves of Chinese corn maple are crushed as they are, or dried and then crushed, water or alcohol such as ethanol, ether, acetone, 1,3-butylene glycol, 1 , 2-Pentanediol, Propylene glycol, Ethyl acetate and other crude extracts, and extracts obtained by stepwise purification of the crude extract with various types of chromatography such as partition extraction and column chromatography Fractions can be used. The leaves or dead leaves of Chinese corn maple may be subjected to the extraction operation as they are, but it is more efficient to perform the extraction after chopping, drying, pulverization and the like. Extraction can be performed by immersing in an extraction solvent. In order to increase the extraction efficiency, the extraction solvent can be stirred, crushed and homogenized in the extraction solvent, or pressure can be applied in the extraction solvent. The extraction temperature is suitably about 5 to 100 ° C., and the extraction time is about 5 minutes to 1 month. These conditions can be set as appropriate.

  The preparation of the present invention can be applied in the form of, for example, a solution such as an aqueous solution, an oil, an emulsion, and a liquid, a semi-solid such as a gel and a cream, and a solid such as a powder, granule, capsule, microcapsule, and solid. . It is prepared in these forms by a conventionally known method, and lotion, emulsion, gel, cream, ointment, plaster, haptic, aerosol, suppository, injection, powder, granule, tablet, pill , Various dosage forms such as syrups and lozenges. These can be applied to the body by applying, sticking, spraying or drinking. Among these dosage forms, lotions, emulsions, creams, ointments, plasters, haps, aerosols and the like, which are external preparations for skin, are suitable.

  The whitening agent containing the Sinaia maple extract of the present invention can be used as a whitening cosmetic or a quasi-drug for whitening. In particular, it has an action to suppress melanin synthesis caused by exposure to ultraviolet rays, so it is effective for measures against sunburn by outdoor activities. Whitening cosmetics, quasi-drugs for whitening, lotion, emulsion, cream, pack, makeup base lotion, makeup cream, foundation, lipstick, eye color, cheek color, hand cream, leg cream, Examples include body lotions and bath additives.

  When the whitening agent of the present invention is used as a whitening cosmetic or a quasi-drug for whitening, oils and fats such as vegetable oils, higher fatty acids, higher alcohols, silicones, anionic surfactants, cationic surfactants, amphoteric surfactants , Nonionic surfactants, preservatives, sugars, sequestering agents, polymers such as water-soluble polymers, thickeners, powder components, UV absorbers, UV blockers, moisturizers such as hyaluronic acid , Fragrance, pH adjuster and the like can be contained. 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 included.

This invention is the invention which paid its attention to the whitening effect of a Sinaia maple maple extract. In particular, it exhibits an inhibitory action on melanin synthesis. It has an effect of suppressing melanin synthesis caused by exposure to ultraviolet rays such as UVB. And it is safe with little cytotoxicity.
It is recognized that the melanin synthesis inhibitory effect of Sinaia maple extract exhibits a concentration-dependent effect. Addition of 0.004 mg / ml extract (ie 0.004 ÷ 1000 (g) ÷ 1 (ml≈g) × 100 = 0.004%) of the melanin synthesis inhibitory effect of B16 mouse melanoma cells in the medium As a result, an inhibitory effect on melanin synthesis was observed. Furthermore, an effect was recognized at 0.1% by weight as an external preparation for skin.
Therefore, it is preferable to add 0.004% or more, preferably 0.1% or more of Sinaia maple extract.
The whitening agent containing the extract of Chinese corn maple can be administered orally or parenterally as a pharmaceutical product.

Preparation of Sinaia maple maple hot water extract 100 g of dried Sinaia maple leaf was placed in 6 L of distilled water and boiled at 100 ° C. for 10 minutes. The obtained hot water extract was freeze-dried to obtain 9 g of Chinese corn maple extract.

Preparation of Sinaia maple maple leaf hot water extract 100 g of dried Sinaia maple maple leaf extract was placed in 6 L of distilled water and boiled at 100 ° C. for 10 minutes. The obtained hot water extract was freeze-dried to obtain 4 g of Chinese corn maple extract.

Preparation of Sinaia maple maple ethanol extract 100 g of dried Syringa maple leaf was soaked in 6 L of 99.5% ethanol for 1 week, and the solvent of the obtained ethanol extract was distilled off to obtain 2 g of Sinaia maple maple extract. Got.

Preparation of Sinaia maple maple dead leaf ethanol extract 100 g of dry seasoner maple maple leaf extract was soaked in 6 L of 99.5% ethanol for 1 week, and the solvent of the obtained ethanol extract was distilled off to give 1 g of Sinosa maple maple leaf extract. An extract was obtained.

Whitening test of human skin model of Chinese corn maple 1. the purpose:
To confirm the effect of Chinese maple maple on melanin synthesis.

2. Method:
(1) Kits and reagents used ・ Three-dimensional skin model (MEL-300-A) (Melanoderm) (Kurashiki Boseki Co., Ltd. (MatTek)) (Asian donor type)
EPI-100LLMM maintenance medium (Kurashiki Spinning Co., Ltd. (MatTek))
・ LDH measurement kit (Wako Pure Chemical Industries, Ltd.)
(2) Specimen Case components were dissolved in DPBS (−) (Dulbecco's modified PBS (−)) at concentrations shown in the following 1 to 8 to prepare specimens.
1. 2% ascorbyl 2-glucoside (hereinafter AA2G) (n = 4)
2. 0.1% AA2G (n = 4)
3. 0.1% extract of Example 1 (n = 4)
4. 0.1% extract of Example 2 (n = 4)
5. None (control) (n = 4)
6. 0.1% extract of Example 3, 0.2% dimethyl sulfoxide (hereinafter DMSO) (n = 4)
7. 0.1% extract of Example 4, 0.2% DMSO (n = 4)
8. 0.2% DMSO (control)

(3) Test method
1. Three-dimensional skin model (MEL-300-A) Melanoderm was opened within 24 hours after delivery, and was prepared for culture in EPI-100LLMM maintenance medium according to the standard method.
2. 100 μl each of the specimen of (2) was administered onto the skin model cup and cultured for 11 days at 37 ° C. and 5% CO ₂ while changing the medium and sample every 48 hours.
At the time of medium exchange, the culture solution was stored frozen, and LDH (lactate dehydrogenase) in the culture solution was measured as a cytotoxicity test.
3. After completion of the culture, a photograph was taken to evaluate the amount of melanin. The tissue was photographed with a video microscope (× 5), luminance analysis (ImageJ 1.33 (National Institutes of Health (NIH))) was performed, the blackness was calculated according to Equation 1, and the whitening effect was evaluated.
The results calculated by the following formula are shown in Table 1 and FIG.
Formula 1: [Blackness (%)] = ([Luminance Maximum Value (Sample)] − [Luminance Average Value (Sample)]) / ([Luminance Maximum Value (Control)] − [Luminance Average Value (Control)]) × 100
The highest luminance value is the highest luminance value in the observation area where no melanin is present.
The average luminance value is an average luminance value of the observation area.
Here, for the value of Control, Sample 5 was used for Samples 1-5, and Sample 8 was used for Samples 6-8. Here, Sample 5 and Sample 8 differed only in the presence or absence of 0.2% DMSO, and the luminance of Sample 5 and Sample 8 matched. Therefore, it is determined that the blackness of the samples 1 to 4 and the samples 6 and 7 can be compared in the same row.
The significant difference test was Student's t-test, and the activity was compared with each control and AA2G at the same concentration.

3. Results (1) Cytotoxicity test The LDH activity of the DPBS (-)-treated skin model medium and other sample-treated LDH activities were comparable, and no cytotoxicity was observed due to the addition of each specimen. The LDH activity of each specimen shown in the graph of FIG. 1 almost overlaps, and it is clear that there is no difference in cytotoxicity due to the addition of each specimen.

(2) Luminance analysis on day 9 of skin model cup culture
Table 2 shows the luminance analysis results on day 9 of the skin model cup culture. This is graphed in FIG.
In the 2% AA2G, 0.1% Chinese corn maple extract added system, a tendency to suppress blackening of the three-dimensional skin model was observed. No difference in blackening suppression tendency was observed between the leaves of Chinese corn maple and dead leaves (comparison between specimens 3 and 4 and comparison between specimens 6 and 7). Samples 6 and 7 containing 100% ethanol extract were blackened when hot water extract of pineapple maple leaves and dead leaves (samples 3 and 4) and 100% ethanol extract (samples 6 and 7) were compared. Excellent suppression effect.
Specimen 3 containing a hot water extract of Chinese corn maple leaf was superior in blackening suppression effect compared to control specimen 5 (p <0.01). Specimen 4 containing a hot water extract of dead leaves of Chinese maple maple was superior to the control specimen 5 in suppressing blackening (p <0.05).
Specimen 6 containing 100% ethanol extract of Chinese maple leaf was significantly superior in blackening suppression effect compared to control specimen 8 (p <0.001). Specimen 6 was also excellent in suppression of blackening (p <0.01) as compared with specimen 2 containing 0.1% AA2G.
Specimen 7 containing a 100% ethanol extract of dead leaves of Chinese maple maple was superior in blackening suppression effect compared to control specimen 8 (p <0.01). Specimen 7 was also excellent in suppression of blackening compared to Specimen 2 containing 0.1% AA2G (p <0.01).
Specimen 7 containing a hot water extract of dead leaves of Chinese maple maple and Sinaia maple maple was superior in the effect of inhibiting blackening (p <0. 0) as compared with Specimen 2 containing Control 8 and 0.1% AA2G. 05).

Whitening test on mouse melanoma of Chinese maple maple 1. the purpose:
To confirm the effect of Chinese maple maple on melanin synthesis.

2. Method:
(1) Cells and reagents used • B16 melanoma (JCRB)
・ MEM medium (Nissui Pharmaceutical Co., Ltd.)
・ Fetal calf serum (Invitrogen)
・ Theophylline (Sigma)
・ Glucosamine (Wako Pure Chemical Industries, Ltd.)
(2) Sample
1. Ascorbic acid (n = 4)
2. Kojic acid (n = 4)
3. Extract of Example 1 (n = 4)

(3) Test method
B16 mouse melanoma cells were seeded in 120,000 cells / well in a 12-well plate in MEM medium containing 0.1% (w / v) glucosamine and cultured for 5 days. Thereafter, the medium was changed to a MEM medium containing 0.03% (w / v) theophylline and the sample was put in, and cultured for 3 days. Samples in the MEM medium were 0.02 and 0.004 mg / ml, respectively. After washing the cells, the cells were solubilized with a 0.1% SDS aqueous solution and the absorbance at 475 nm and 260 nm was measured to give S475 and S260. The melanin synthesis rate was calculated according to Equation 1 using the absorbance at 475 nm and 260 nm of cells (control) cultured in a medium to which no sample was added as C475 and C260.

(Equation 1)
Melanin synthesis rate (%) = {(S475 / S260) / (C475 / C260)} × 100 (Formula 1)

Ascorbic acid and kojic acid, which are widely used as whitening components, were used as positive control samples.
The significant difference test was Student's t-test, and the activity was compared with control, kojic acid and vitamin C at the same concentration.

3. Results Table 3 shows the melanin synthesis rate. The numerical values in Table 3 are graphed in FIG. Inhibition of melanin synthesis was observed in the Chinese corn maple extract addition system. Melanin synthesis inhibitory effect comparable to that of kojic acid and vitamin C. In the system to which 0.02 mg / ml of the extract of Example 1 was added, superior melanin synthesis compared to control and 0.02 mg / ml kojic acid An inhibitory effect was shown (p <0.05). The system to which the extract of Example 1 was added at 0.004 mg / ml showed an excellent inhibitory effect on melanin synthesis compared with 0.004 mg / ml vitamin C (p <0.05).

Formulation Example 1 Lotion Ingredient Amount (% by mass)
1. Glycerin 9.5
2. 1,3-butylene glycol 4.5
3. Glucose 1.5
4). Ethanol 5
5. Carboxyvinyl polymer 0.02
6). Dipotassium glycyrrhizinate 0.1
7). Sodium hyaluronate 0.1
8). Extract of Example 1 0.1
9. Citric acid 0.05
10. Sodium citrate 0.1
11. Ion-exchanged water remaining 12. Potassium hydroxide 0.01

At room temperature, components 1 to 10 were added to component 11 and dissolved by stirring, and component 12 was added and dissolved uniformly to obtain a lotion.

Formulation Example 2 Cream Ingredient Amount (% by mass)
1. Stearyl alcohol 6
2. Stearic acid 2
3. Squalane 9
4). Octild decanol 10
5.1,3-Butylene glycol 8
6). Polyethylene glycol 1500 4
7). POE (25) cetyl alcohol ether 3
8). Glyceryl monostearate 2
9. Purified water remaining 10. Extract of Example 2 0.004

Components 1 to 4 are heated and dissolved at 80 ° C. to obtain an oil phase. Ingredients 5-9 are heated and dissolved at 70 ° C. to obtain an aqueous phase. The aqueous phase was gradually added to the oil phase to emulsify, and the mixture was cooled to 40 ° C. while stirring. After component 10 was added, the mixture was further stirred and cooled to 30 ° C. to obtain a cream.

Formulation Example 3 Pack Ingredient Amount (% by mass)
1. Polyvinyl alcohol 15
2. Carboxymethylcellulose 5
3. 1,3-butylene glycol 5
4). Ethanol 12
5. Extract of Example 3 1
6). POE oleyl alcohol ether 0.5
7). Citric acid 0.02
8). Sodium citrate 0.04
9. Purified water residue

Ingredients 3, 6-8 are mixed and heated to 80 ° C. Add 1 and 2 to this and stir. After confirming dissolution, cool to 40 ° C. Next, ingredients 4 and 5 are added and stirred, and further cooled to 30 ° C.

Claims (6)

  A whitening agent comprising an extract from Chinese maple maple as an active ingredient.   A melanin synthesis inhibitor characterized by containing an extract from Chinese maple maple as an active ingredient.   The agent according to claim 1 or 2, wherein the extract is an extract from leaves of Chinese corn maple.   The extract according to any one of claims 1 to 3, wherein the extract is a hot water extract or an ethanol extract.   It is a skin external preparation, The agent in any one of Claims 1-4. The agent according to any one of claims 1 to 5, comprising 0.0004% by weight or more of an extract.