JP3140357B2 - Skin whitening agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to ginger (Zingiber).
aceae) A skin whitening preparation that is effective for preventing and improving pigmentation, spots, freckles, melasma, etc. after sunburn by suppressing the production of melanin by incorporating an extract of the genus Zingiber. About.

[0002]

2. Description of the Related Art Although there are some unclear points about the mechanism of the occurrence of skin spots and the like, melanin pigments are generally formed due to hormonal abnormalities and stimulation of ultraviolet rays from sunlight. It is believed to be abnormally deposited within. This melanin pigment, which causes skin coloring, is produced in melanin-producing granules (melanosomes) in melanocytes (melanocytes) between the epidermis and dermis,
The generated melanin diffuses to adjacent cells by osmosis. The biochemical reaction in this melanocyte is estimated as follows. That is, tyrosine, which is an essential amino acid, is converted into dopaquinone by the action of the enzyme tyrosinase, and the process in which it is converted to black melanin via a red pigment and a colorless pigment by an enzymatic or non-enzymatic oxidative action is a melanin pigment production process. Therefore, suppressing the action of tyrosinase, which is the first step in the reaction, is important for suppressing melanin production.

[0003]

However, compounds that suppress the tyrosinase action, except for hydroquinone, have very slow onset of their effects, so that the effect of improving skin pigmentation is not sufficient. On the other hand, although hydroquinone is recognized as having an effect, its use is generally restricted because of its sensitizing properties. In order to improve the safety, attempts have been made to use monoesters or alkyl monoethers of higher fatty acids (Japanese Patent Application Laid-Open No. 58-154507), but the esters are decomposed by hydrolytic enzymes in the body. Therefore, it is not always safe, and ethers which do not sufficiently satisfy safety requirements have not been obtained.

[0004]

As a solution to these problems, the present inventors examined the effect of inhibiting melanin production on a wide variety of substances, and found that ginger (Zingib)
The present inventors have found that an extract of a plant belonging to the genus Zingiber (Eraceae) has a melanin production inhibitory action and a tyrosinase inhibitory action, and have completed the present invention.
Ginger (Zingiberaceae)
There has been no report on the melanin production-inhibitory effect of an extract of a genus plant, and no application to a whitening agent has been known. The present inventors have completed the present invention based on the above findings.

That is, the present invention relates to ginger (Zingiberac).
eae) An external preparation for whitening skin, comprising an extract of a plant belonging to the genus Zingiber.

Hereinafter, the configuration of the present invention will be described in detail. Ginger (Zingiberacea) used in the present invention
The e) family Jingiba (Zingiber) plants of the genus, Rumupuyan (Lempuyang, scientific name: Zing
iber aromaticumMal. ) And Bengle (scientific name: Zingiber cas)
sumunar Roxb. ) Are preferred. Among them, bungre is what is called pontsu ginger. These are plants that grow especially on dry grasslands and pastures in Indonesia. The extract used in the present invention, the leaves of the above-mentioned plants, stems including rhizomes, fruits, etc., after soaking or heating and refluxing the whole plant with an extraction solvent, filtration,
It is obtained by concentration. The extraction solvent used in the present invention is not particularly limited as long as it is a solvent usually used for extraction. In particular, an organic solvent such as alcohols such as methanol and ethanol, aqueous alcohols, acetone, and ethyl acetate is used alone or in combination. Can be.

The ginger (Zingiberacea) of the present invention
e) The amount of the extract of the plant belonging to the genus Zingiber is from 0.005 to 20.0 as a dry product in the total amount of the external preparation.
% By weight, preferably 0.01 to 10.0% by weight.
If the amount is less than 0.005% by weight, the effects of the present invention are not sufficiently exhibited, and if the amount is more than 20.0% by weight, it is not preferable because formulation is difficult. Further, even if the content is 10.0% by weight or more, the effect is not so much improved.

[0008] In addition to the above essential components, the skin whitening preparation for external use of the present invention contains components usually used for skin external preparations such as cosmetics and pharmaceuticals, for example, other whitening agents, humectants, and the like.
Antioxidants, oily components, UV absorbers, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water,
Various skin nutrients and the like can be appropriately compounded as needed.

Other sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and derivatives thereof, and licorice extract Thing, glabridine, hot water extract of fire thorn fruit, various crude drugs, tocopherol acetate,
Drugs such as glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate,
Other whitening agents such as ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, mannose,
Saccharides such as sucrose and trehalose can also be appropriately blended.

The whitening skin external preparation of the present invention includes, for example, ointments, creams, emulsions, lotions, packs, bath preparations, etc.
Any conventional skin external preparation may be used,
The dosage form is not particularly limited.

[0011]

Next, the present invention will be described in more detail by way of examples. Note that the present invention is not limited by this. The compounding amount is% by weight. Prior to the examples, test methods and results regarding the melanin-suppressing effect, tyrosinase activity-inhibiting effect, and whitening effect of the plant extract of the present invention will be described.

Test Methods and Results Rhizome portion 50g of the Sample Preparation (1) Rumupuyan (Lempuyang) extract Rumupuyan (Lempuyang)
Was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 2.5 g of an ethanol extract. This extract is
After dissolving 1% in MSO and diluting this solution to adjust the concentration, the following experiment was performed using this.

(2) Bengle extract 50 g of the rhizome of Bengle was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 67 mg of an ethanol extract. This extract was added to DMSO for 1
%, And the concentration was adjusted by diluting this solution. Using this, the following experiment was performed.

2. Cell culture method B16 melanoma cultured cells derived from mice were used. 1
0% FBS and theophylline (0.09 mg / ml)
Was cultured in a CO ₂ incubator (95% air, 5% carbon dioxide) at 37 ° C. in an Eagle MEM medium containing After 24 hours of culture, the sample solution is added to a final concentration (concentration in terms of dry extract) of 10 ^-3 to 10 ^-5 % by weight, and the culture is further continued for 3 days. Judgment and the tyrosinase activity inhibitory effect were measured.

3. Visual measurement of the amount of melanin Place the diffusion plate on the lid of the well plate, observe the amount of melanin in the cells with an inverted microscope, and check the ginger (Zingiberac).
eae) It was compared with the case of a sample (reference) to which no extract of the Zingiber genus plant was added. The results are shown in Table 1. Further, as a reference example, the same test as described above was carried out for an extract of mussels (Lamiaceae: Subfamily Poaceae) and hydroquinone, which are already known to have a melanin production inhibitory action. Table 1 also shows the results.

<Judgment Criteria> 白: White (melanin content) Δ: Slightly white (melanin content) ×: Standard (melanin content)

4. Measurement of tyrosinase activity Before measurement, the medium in the wells is removed and washed twice with 100 μl of PBS. 45 μl of 1% Triton-X in each well
(Rohm and Haas product name, surfactant) containing PBS is added. Shake the plate for 1 minute, break the cell membrane well, and use a microplate reader for 475n.
The absorbance at m was measured, and this was taken as the absorbance at 0 minutes. Thereafter, 5 μl of a 10 mM L-DOPA solution was quickly added, and the mixture was transferred to a 37 ° C. incubator and reacted for 60 minutes. The plate was shaken for 1 minute, and the absorbance (475 nm) at 60 minutes was measured. The tyrosinase activity ratio (%) was defined as the ratio of the absorbance difference of the sample with the plant extract to the absorbance difference between the time of 0 minute and the time of 60 minutes in the case of the sample to which no plant extract was added (control). Table 1 shows the results. In addition, as a reference example, the same test as described above was carried out for an oyster ethanol extract and hydroquinone, which are already known to have a tyrosinase activity inhibitory action. Table 1 also shows the results. In addition,
In the table,-means that no significant difference was observed within 5% of the risk ratio as compared with the control.

[0018]

[Table 1]

5. Whitening effect test [Test method] 64 days of subjects exposed to sunlight in summer for 4 hours (2 hours a day for 2 days). Was applied once every morning and evening for 4 weeks. The panel was divided into eight groups and divided into eight groups, and the test was performed according to the following formulation. (Alcohol phase) 95% ethyl alcohol 55.0% by weight Polyoxyethylene (25 mol) hydrogenated castor oil ether 2.0 Antioxidant / preservatives Appropriate amount Perfume Appropriate amount Drug (Table 2) (Aqueous phase) Glycerin 5.0 Sodium hexametaphosphate Appropriate amount Ion-exchange water Residue <Production method> Prepare an aqueous phase and an alcohol phase, respectively, and then mix and solubilize both.

[Evaluation method] The lightening effect after use was determined based on the following criteria. <Judgment criteria> ：: When the ratio showing significant effect and effectiveness among the subjects is 80% or more 割 合: The ratio showing significant effect and effectiveness among the subjects is 50% or more
Less than 80% △: The proportion of the test subjects showing excellent and effective is 30% or more
Less than 50% ×: The proportion of subjects showing excellent and effective is less than 30%

A sample having the composition described in the above test method was prepared, and the whitening effects were compared using the agents shown in Table 2.
The results are shown in Table 2.

[0022]

[Table 2]

The Lumpuyan extract and the Bungre extract shown in Table 2 were obtained by reducing the rhizome of each plant by heating in ethanol, filtering, concentrating and drying.

[0024] Table 2 more As is apparent, the effect after exposure to sunlight prevents the deposition of an excess of melanin who was added Rumupuyan extract or Benguru extract, preventing to become dark complexion It was recognized that.

Example 1 Cream (Formulation) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Lumpuyan methanol extract 0.01 Caustic potassium 0 propylene glycol and Rumupuyan meth <br/> Nord extract and caustic potash was added dissolved in .2 sodium bisulfite 0.01 preservative qs perfume qs ion exchanged water balance (preparation method) ion-exchanged water, heated to 70 ° C.
(Aqueous phase). Mix other ingredients, heat and melt at 70 ° C
(Oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is maintained for a while to cause a reaction.
Thereafter, the mixture is uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

Example 2 Cream (Formulation) Stearic acid 2.0% by weight Stearyl alcohol 7.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl alcohol ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 Bungre ethanol extract 0.05 Sodium bisulfite 0.03 Ethyl paraben 0.3 Perfume Appropriate amount Ion exchange water Residue (Production method) Propylene glycol in ion exchange water And add
Heat and maintain at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase, pre-emulsified, homogenized with a homomixer, and cooled to 30 ° C. with good stirring.

Example 3 Cream (Formulation) Solid paraffin 5.0% by weight Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monolaurate 2 0.0 Soap powder 0.1 Borax 0.2 Lumpuyan acetone extract 0.05 Bungre ethanol extract 0.05 Sodium bisulfite 0.03 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchanged water Residue (Production method) To ion-exchanged water Add soap powder and borax, heat and dissolve and maintain at 70 ° C (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After completion of the reaction, the mixture is uniformly emulsified with a homomixer, and cooled to 30 ° C. while stirring well after emulsification.

Example 4 Emulsion (formulation) 2.5% by weight of stearic acid Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (trade name: Carbopol 941, BF Goodrich Chemical Company) Lumpuyan acetate ethyl ester extract 0.01 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion exchange water Residue (Preparation method) Dissolve carboxyvinyl polymer in a small amount of ion exchange water (phase A). Polyethylene glycol 1500 and triethanolamine are added to the remaining ion-exchanged water, dissolved by heating, and kept at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase to perform preliminary emulsification, the phase A is added, and the mixture is uniformly emulsified with a homomixer. After the emulsification, the mixture is cooled to 30 ° C. while stirring well.

Example 5 Emulsion (Formulation) Microcrystalline wax 1.0% by weight Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 mol) ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Bungreacetone extract 10.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water Residue (Preparation method) Add propylene glycol to ion-exchanged water ,
Heat and maintain at 70 ° C. (aqueous phase). The other components are mixed, heated and melted and kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added thereto, and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C with good stirring.

Example 6 Jelly (Formulation) 95% ethyl alcohol 10.0% by weight Dipropylene glycol 15.0 Polyoxyethylene (50 mol) oleyl alcohol ether 2.0 Carboxyvinyl polymer 1.0 (Product name: Carbopol) 940, BF Goodrich Chemical Company Caustic soda 0.15 L-arginine 0.1 Lumpuyan 50% aqueous ethanol extract 7.0 Sodium 2-hydroxy-4-methoxybenzophenonesulfonate 0.05 Ethylenediaminetetraacetate-3 sodium 2 water 0.05 Methyl paraben 0.2 Carbopol 940 perfume qs ion exchanged water balance (preparation method) ion-exchanged water were uniformly dissolved, whereas, Rumupuyan 50% ethanol aqueous 95% ethanol Extract, dissolving polyoxyethylene (50 mol) oleyl alcohol ether, is added to the aqueous phase. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 7 Serum (Prescription) (Phase A) Ethyl alcohol (95%) 10.0% by weight Polyoxyethylene (20 mol) octyldodecanol 1.0 Pantothenyl ethyl ether 0.1 Bungre methanol extraction Product 1.5 Methyl paraben 0.15 (B phase) Potassium hydroxide 0.1 (C phase) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 (Product name: Carbopol) 940, BFGoodrich Chemical company) Purified water residue (Preparation method) Dissolve A phase and C phase uniformly, and add A to C phase
Add phases and solubilize. Next, after adding the phase B, filling is performed.

Example 8 Pack (Formulation) (A phase) Dipropylene glycol 5.0% by weight Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) Lumpuyan methanol extract 0.01 Olive oil 5.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Fragrance 0.2 (Phase C) Sodium bisulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, Degree of polymerization 2,000) Ethanol 7.0 Purified water residue (Production method) ) A phase, B phase, and C phase are each uniformly dissolved, and the B phase is added to the A phase to be solubilized. Next, this is added to the C phase and then filled.

Example 9 Solid foundation (formulation) Talc 43.1% by weight Kaolin 15.0 Sericite 10.0 Zinc white 7.0 Titanium dioxide 3.8 Yellow iron oxide 2.9 Black iron oxide 0.2 Squalane 8 2.0 Isostearic acid 4.0 POE sorbitan monooleate 3.0 Isocetyl octoate 2.0 Bungreethanol extract 1.0 Preservatives Appropriate amount Flavors Appropriate amount (Preparation method) Powdery components of talc to black iron oxide are sufficiently mixed in a blender. Then, an oil component of squalane to isocetyl octanoate, a Bungre ethanol extract, a preservative, and a fragrance are added, kneaded well, and the mixture is filled into a container and molded.

Example 10 Emulsion type foundation (cream type) (Prescription) (Powder part) Titanium dioxide 10.3% by weight Sericite 5.4 Kaolin 3.0 Yellow iron oxide 0.8 Bengala 0.3 Black iron oxide 0.2 (oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (aqueous phase) Purified water 50.0 1,3-butylene glycol 4.5 Lumpuyan Ethanol extract 1.5 Sorbitan sesquioleate 3.0 Preservatives Appropriate amount Flavors Appropriate amount (Preparation method) After heating and stirring the aqueous phase, a well-mixed and pulverized powder portion is added, followed by homomixer treatment. Further, the oil phase mixed by heating is added, and the mixture is treated with a homomixer. Then, a fragrance is added with stirring, and the mixture is cooled to room temperature.

[0035]

As described above, the external preparation for whitening skin of the present invention has an inhibitory effect on melanin production and an inhibitory effect on tyrosinase activity, and is effective in preventing pigmentation, spots, freckles, liver spots, etc. after sunburn. It has excellent effects on lightening and whitening, and also has excellent safety.

──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Masako Naganuma 1050 Nippacho, Kohoku-ku, Yokohama, Kanagawa Prefecture Inside Shiseido Daiichi Research Center Co., Ltd. (72) Yoshihiro Yokokawa 1050 Nippacho, Kohoku-ku, Yokohama, Kanagawa, Japan (56) References JP-A-8-231352 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K ⁷ /00-7/48 A61K 35 / 78 CA (STN)

Claims (4)

(57) [Claims] 1. Ginger (Zingiberacea)
e) An external preparation for skin whitening, comprising an extract of a plant belonging to the genus Zingiber. 2. Ginger (Zingiberacea)
e) The plant belonging to the genus Zingiber is Lump
Yan (Lempuyang, scientific name: Zingiber
aromaticum Mal. 3. The external preparation for whitening skin according to claim 1, wherein 3. Ginger (Zingiberacea)
e) The plant belonging to the genus Zingiber (Zingiber) is Bengle (scientific name: Zingibercassu)
munar Roxb. 3. The external preparation for whitening skin according to claim 1, wherein 4. Ginger (Zingiberacea)
e) The amount of the extract of the plant belonging to the genus Zingiber is from 0.005 to 20.0% by weight.
A skin whitening agent for external use according to any one of Items 1 to 3.