JPH0920635A - Whitening skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a whitening skin preparation for external use, having melanogenesis suppressing action and tyrosinase activity inhibiting action and effective in preventing and improving pigmentation after sunburn, stain, freckle, chloasma, etc. SOLUTION: This skin preparation for external use is obtained by blending extracts of one or more kinds of plants selected from Curcuma xanthorrhiza, Curcuma heyneana Val. and Curcuma aeruginosa belonging to the genus Curcuma of the family Zingiberacea, especially a which grow in indonesian dried grassland, pasture, etc., in an amount of 0.005-20wt.%, preferably 0.01-10wt.% as a dried material based on total amount of the preparation for external use. Other whitening agent, a humectant, an antioxidant, an oily component, an ultraviolet light absorbent, a surfactant, a thickener, alcohols, powder ingredient, a coloring material, an aqueous ingredient, water, various kinds of skin nutrients, etc., can properly be blended in the skin preparation for external use and the skin preparation for external use can be prepared in ointment, cream, lotion, pack, bathing agent, etc. The extract is obtained by immersing the leaf, stem containing underground stem, bark, fruit, etc., or total grass of the plant into an extracting solvent (e.g. ethanol) or heating the plant therein under reflux, filtering the mixture and concentrating the filtrate.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention is directed to specific ginger (Zingib).
eraceae) Curcuma (Curcuma) genus plant extract is combined to suppress melanin production and to prevent and improve pigmentation, spots, freckles, and liver spots after sunburn. Regarding

[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 into adjacent cells by the osmotic effect. The biochemical reaction in this melanocyte is presumed to be 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 of 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. Therefore, in order to improve its safety, attempts have been made to use higher fatty acid monoesters or alkyl monoethers (JP-A-58-154507), but the esters are decomposed by a hydrolase in the body. Therefore, it is not always safe, and ethers have not been sufficiently satisfactory in terms of safety.

[0004]

Therefore, as a result of investigating the melanin production inhibitory effect of a wide variety of substances for solving these problems, the present inventors have found that a specific ginger (Zingiberaceae) family Curcuma plant It was found that the extract of the above has an action of suppressing melanin production and an inhibitory action of tyrosinase, and completed the present invention. Ginger (Zingiberaceae) Family Curcuma
A report on the melanin production inhibitory action of the extract of the genus plant has hitherto been disclosed in JP-A-5-255061, in which a substance derived from curcumin obtained from Curcuma domestica is used as a melanin production inhibitor for an external preparation. Only the one mixed therein is known, and other plants are not known at all.

That is, the present invention relates to ginger (Zingiberac
eae) Curcuma genus Tem Rawak (Tem)
u lawak, scientific name: Curcuma xanthorrhiza, Temu girin, scientific name: Curcuma he
yneana Val.) and Temu ire
ng, scientific name: Curcuma aeruginosa), and one or more plant extracts selected from the group is a whitening skin external preparation.

The structure of the present invention will be described in detail below. Temu lawa of the genus Curcuma of the ginger (Zingiberaceae) family used in the present invention
k, Scientific name: Curcuma xanthorrhiza), Tem Gillin (T
emu giring, scientific name: Curcuma heyneana Va
l.) and Temu ireng (scientific name: Curcuma aeruginosa) are plants that especially grow on the dry grasslands and grasses of Indonesia. Extracts used in the present invention, the leaves of the above plants, stems including rhizomes, fruits, etc.
After immersing the whole plant with the extraction solvent or heating to reflux,
Obtained by filtration and concentration. The extraction solvent used in the present invention may be any solvent used in ordinary extraction,
In particular, alcohols such as methanol and ethanol, hydroalcohols, organic solvents such as acetone and ethyl acetate can be used alone or in combination.

The content of the plant extract in the present invention is 0.005 to 20.0% by weight, preferably 0.01 to 10.0% by weight, as a dried product, based on the total amount of the external preparation. 0.
If it is less than 005% by weight, the effect of the present invention is not sufficiently exhibited, and if it exceeds 20.0% by weight, formulation is difficult, which is not preferable. Further, even if the content is 10.0% by weight or more, the effect is not so much improved.

In addition to the above-mentioned essential components, the external whitening agent for skin whitening of the present invention also contains components that are usually used in external skin externalizing agents such as cosmetics and pharmaceuticals, such as other whitening agents and moisturizers.
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.

In addition, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extraction Substance, glabridin, hot water extract of fruits of fire thorns, 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,
Sugars such as sucrose and trehalose can also be appropriately blended.

The external whitening agent for whitening of the present invention includes, for example, ointments, creams, emulsions, lotions, packs, bath agents and the like.
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 Examples, test methods and results of the melanin suppressing effect, tyrosinase activity inhibiting effect and whitening effect of the plant extract of the present invention will be described.

Test Method and Results 1. Sample preparation (1) Temu lavak extract Temu lavak rhizome 5
0 g was immersed in ethanol at room temperature for 1 week and the extract was concentrated to obtain 1.4 g of an ethanol extract. This extract was dissolved in DMSO at 1%, the concentration was adjusted by diluting this solution, and the following experiment was performed using this.

(2) Temu girin
g) Extraction liquid 50 g of the rhizome of Temu girling was immersed in ethanol at room temperature for 1 week, and the extraction liquid was concentrated to obtain 2.3 g of an ethanol extract. This extract was dissolved in DMSO at 1%, the concentration was adjusted by diluting this solution, and the following experiment was performed using this.

(3) Temu iren
g) Extract liquid Temu irengue rhizome 5
0 g was immersed in ethanol for 1 week at room temperature and the extract was concentrated to obtain 2.8 g of ethanol extract. This extract was dissolved in DMSO at 1%, the concentration was adjusted by diluting this solution, and the following experiment was performed using this.

2. Cell culture method B16 melanoma cultured cells derived from mice were used. 1
0% FBS and theophylline (0.09 mg / ml)
The cells were cultured in an Eagle MEM medium containing C. in a CO ₂ incubator (95% air, 5% carbon dioxide) at 37 ° C. After 24 hours of culturing, the sample solution was added so as to have a final concentration (concentration of extracted dry matter) of 10 ^-2 to 10 ^-5 % by weight, culturing was continued for another 3 days, and the melanin production amount was visually sensed by the following method. The determination and the tyrosinase activity inhibitory effect were measured.

3. Visual perception of melanin amount Place a diffusion plate on the lid of the well plate, observe the intracellular melanin amount with an inverted microscope, and ginger (Zingiberac
It compared with the case of the sample (reference | standard) which did not add the extract of Curcuma genus (eae) family. The results are shown in Table 1. In addition, as a reference example, the same test as above was carried out on an extract of Kaigai (Lamiaceae, Odorikosou Subfamily), which is already known to have an action of suppressing melanin production. Table 1 also shows the results. Further, in the table, "toxic" means that it is cytotoxic.

<Judgment Criteria> ◯: White (amount of melanin) Δ: Slightly white (amount of melanin) ×: Reference (amount of melanin)

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. Then, 5 μl of 10 mM L-DOPA solution was quickly added, and the mixture was transferred to an incubator at 37 ° C. 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. Further, as a reference example, the same test as above was carried out on an ethanol extract of mussel, which is already known to have a tyrosinase activity inhibitory action. Table 1 also shows the results. In the table, "toxic" means that cytotoxicity was observed, and "-" means that no significant difference was observed within a risk rate of 5% as compared with the control.

[0019]

[Table 1] ──────────────────────────────────── Test melanogenesis visual evaluation Tyrosinase activity rate ( %) ──────── ─────────── ──────────── Concentration (wt%) 10 ^-5 10 ^-4 10 ^-3 10 ^-2 10 ^-5 10 ^-4 10 ^-3 10 ^-2 ──────────────────────────────────── Rawak extract × × ○ Toxic − 81 23 Toxic thyme gillin extract × × △ Toxic 81 − − Toxic thyme and ylen extract × × ○ Toxic − − 46 Toxic cabbage extract × × × × − − − 55 ── ───────────────────────────────────

[5] Whitening test [Test method] 40 subjects exposed to sunlight in summer for 4 hours (2 hours per day for 2 days) each sample from 5 days after the day of sun exposure to the skin of the upper arm inner skin Was applied once each morning and evening for 4 weeks. The panel was divided into 8 groups, and 5 groups were prepared, and the tests were conducted according to the formulations shown below. (Alcohol phase) 95% Ethyl alcohol 55.0% by weight Polyoxyethylene (25 mol) hydrogenated castor oil ether 2.0 Antioxidant / preservative proper amount Fragrance proper amount drug (listed in Table 2) (water phase) glycerin 5.0 Sodium hexametaphosphate Suitable amount Ion-exchanged water Residue <Production method> An aqueous phase and an alcohol phase are prepared, respectively, and then both are mixed and solubilized.

[Evaluation Method] The lightening effect after use was judged based on the following judgment 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
When less than 50% x: When the ratio of markedly effective or effective among the subjects is less than 30%

Samples having the blending composition described in the above test method were prepared and the whitening effect was compared using the agents shown in Table 2.
The results are shown in Table 2.

[0023]

[Table 2] ────────────────────────── Drug compounding amount (% by weight) Effect ────────── ──────────────── Additive- × Hydroquinone 1.0 △ Tem-rawak extract 0.1 ○ Tem-rawak extract 1.0 ○ Tem-rawak extract 10. 0 ◎ Tem Gillin extract 0.1 ○ Tem Gillin extract 1.0 ○ Tem Gillin extract 10.0 ◎ Tem illen extract 0.1 ○ Tem illen extract 1.0 ○ Tem illen Extract 10.0 ◎ ───────────────────────────

In addition, the tem-rawak extract, tem-
The gillin extract and tem iren extract are obtained by heating and reducing the rhizomes of each plant in ethanol, filtering and concentrating and drying.

As is clear from Table 2, the effect after exposure to sunlight was that the addition of the tem-rawak extract, tem-gillin extract or tem-yrene extract resulted in the deposition of excess melanin pigment. It has been found to prevent and prevent darkening.

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 Temrawak methanol extract 0. 01 Caustic potassium 0.2 Sodium bisulfite 0.01 Preservative Suitable amount Fragrance Suitable amount Ion-exchanged water Residual (production method) Ion-exchanged water with propylene glycol and tem
Rawaqua methanol extract and caustic potash were added and dissolved, and the mixture was heated and kept at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). Add the oil phase gradually to the water phase,
After all the ingredients have been added, the temperature is maintained for a while to cause a reaction. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

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 Temgiline ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Fragrance suitable amount Ion-exchanged water Residual (production method) To ion-exchanged water Add propylene glycol,
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 aqueous phase to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough 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 Tem-Ilenacetone extract 0.05 Tem-rawak Ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water Residual (manufacturing method) Soap powder and borax are added to ion-exchanged water, and the mixture is heated and melted and kept at 70 ° C (water 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 the reaction is completed, the mixture is uniformly emulsified with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

Example 4 Emulsion (formulation) Stearic acid 2.5% by weight Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 3. 0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (Brand name: Carbopol 941, BFGoodrich Chemical company) Temgiline acetic acid ethyl ester extract 0.01 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Perfume proper amount Ion Exchanged water Residue (production method) A carboxyvinyl polymer is dissolved in a small amount of ion exchanged 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 tem-yreneacetone extract 10.0 sodium bisulfite 0.01 ethylparaben 0.3 perfume proper amount ion-exchanged water residual (manufacturing) propylene glycol in ion-exchanged water In addition,
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 wt% dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 1.0 (trade name: Carbopol 940, BFGoodrich Chemical company) Caustic soda 0.15 L-Arginine 0.1 Temrawak 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate-3 sodium-2 Water 0.05 Methylparaben 0.2 Perfume Appropriate amount Ion-exchanged water Residual (Production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while Tem-Rawak 50% ethanol aqueous solution extract and polyoxyethylene (in 95% ethanol) 50 moles) oleyl Was dissolved Le call ether, is added to the aqueous phase. Next, after adding other ingredients, caustic soda,
Thicken by neutralizing with L-arginine.

Example 7 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Weight Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Temgiline Methanol extract 1.5 Methylparaben 0.15 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium hydrogen sulfite 0.03 Carboxyvinyl polymer 0.2 (trade name: Carbopol 940, BFGoodrich Chemical company) Purified water Residual (manufacturing method) Phases A and C are uniformly dissolved, and A is added to phase C
Add phases and solubilize. Next, after adding the phase B, filling is performed.

Example 8 Pack (formulation) (Phase A) 5.0% by weight dipropylene glycol Polyoxyethylene (60 moles) hydrogenated castor oil 5.0 (Phase B) tem-ylene methanol extract 0.01 Olive oil 5 0.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Perfume 0.2 (Phase C) Sodium hydrogen sulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, degree of polymerization 2,000) Ethanol 7.0 Purified water Residue (Manufacturing method) Phase A, phase B, and phase C are uniformly dissolved,
Add phase B to phase and solubilize. 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 0.0 isostearic acid 4.0 POE sorbitan monooleate 3.0 isocetyl octoate 2.0 tem-rawak ethanol extract 1.0 preservative appropriate amount perfume appropriate amount (manufacturing process) Talc to black iron oxide powder component with a blender Mix well and add to it squalane to isocetyl octoate oil component, tem-rawak ethanol extract, preservative,
Add fragrance and knead well, then fill and mold in a container.

Example 10 Emulsion type foundation (cream type) (Prescription) (Powder part) Titanium dioxide 10.3 wt% 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 (water phase) purified water 50.0 1,3-butylene glycol 4.5 system -Gillin ethanol extract 1.5 Sorbitan sesquioleate ester 3.0 Preservative proper amount Perfume proper amount (Production method) After heating and stirring the water phase, a powder portion thoroughly mixed and pulverized is added and treated with a homomixer. 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.

[0036]

Industrial Applicability As described above, the whitening skin external preparation of the present invention has a melanin production inhibitory action and a tyrosinase activity inhibitory action, and is effective in treating pigmentation, stains, freckles, melasma, etc. after sunburn. It has excellent effects in lightening and whitening, and also in safety.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Masako Naganuma Masako Naganuma 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Shiseido Daiichi Research Center Co., Ltd.

Claims (2)

[Claims] 1. A Temu lawak of the genus Curcuma of the Zingiberaceae family,
Scientific name: Curcuma xanthorrhiza), Tem Gillin (Tem)
u giring, scientific name: Curcuma heyneana Val.) and Temu ireng, scientific name: Curc
uma aeruginosa), and 1 or 2 or more kinds of plant extracts selected from the above. 2. The amount of the plant extract blended is 0.005-2.
The external preparation for whitening skin according to claim 1, which is 0.0% by weight.