JP3263246B2 - External preparation for skin - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

This invention relates to Curen.
The present invention relates to an external preparation for skin which is effective in preventing and improving pigmentation, spots, freckles, melasma and the like after sunburn by incorporating an extract of the present invention.

[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 have studied the effect of inhibiting melanin formation on a wide variety of substances.
en, scientific name: Psoraleamexicana Vail) was found to have a melanin production inhibitory action and a tyrosinase inhibitory action, and completed the present invention. There has been no report on the melanin production inhibitory effect of the extract of Curen, and no application to a whitening agent is known. The present inventors have completed the present invention based on the above findings.

[0005] That is, the present invention relates to Cure
n, Scientific name: Psoralea mexicana Vail) is an external preparation for skin characterized by incorporating an extract. The external preparation of the present invention is preferably a skin whitening external preparation.

Hereinafter, the configuration of the present invention will be described in detail. Curen used in the present invention is a plant that grows in dry grasslands and grasses in South America, particularly the Andes. The extract used in the present invention is obtained by immersing or heating and refluxing the whole curen such as leaves and stems or fruits together with an extraction solvent, followed by filtration and 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 amount of the curen extract in the present invention is 0.005 to 20.0% as a dry matter 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-mentioned essential components, the skin external preparation of the present invention contains components usually used in skin external preparations such as cosmetics and pharmaceuticals, for example, other whitening agents, moisturizing agents, antioxidants, and oily components. , UV absorbers, surfactants, thickeners,
Alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients, and the like can be appropriately added as necessary.

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 Products, 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,
Sugars such as sucrose and trehalose can also be appropriately blended.

The external preparation for skin of the present invention may be any of those conventionally used in external preparations for skin, such as ointments, creams, emulsions, lotions, packs, bath preparations, etc., and 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 Preparation of Sample 50 g of stem and branch portions of Curen were immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 8.0 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. 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 ^-2 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 A diffusion plate was placed on the lid of the well plate, and the amount of melanin in the cells was observed with an inverted microscope, and compared with the case of the sample without the Curen extract (reference). The results are shown in Table 1. In addition, as a reference example, the same test as described above was performed on a scallop extract (Lamiaceae, Scrophulariaceae) already known to have a melanin production inhibitory action. Table 1 also shows the results. In the table,
Toxic means cytotoxic.

<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 to
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 inhibition rate (%) was defined as the decrease in the absorbance difference of the sample to which the curen extract was added relative to the absorbance difference between the time of 0 minute and the time of 60 minutes in the case of the sample without the curen extract (control). Table 1 shows the results. In addition, as a reference example, the same test as described above was conducted on an ethanol extract of oyster, 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 5% of the risk ratio as compared with the control.

[0017]

[Table 1] ──────────────────────────────────── Test Melanin production visual evaluation Tyrosinase activity inhibition rate (%) ──────── 濃度 Concentration (% by weight) 10 ^-5 10 ^-4 10 ^-3 10 ^-2 10 ^-5 10 ^-4 10 ^-3 10 ^-2 ──────────────────────────────────── Curen extract × × ○ Toxicity 11 17 46 Toxicity Snail extract × × × × − − − 55 ──────────────────────────── ────────

5. Skin whitening effect test [Test method] For each of the 40 upper subject's upper arm skins exposed to sunlight in the summertime for 4 hours (2 hours a day for 2 days), each sample was started 5 days after the sun exposure. Was applied once every morning and evening for 4 weeks. The panel was divided into eight groups and divided into five 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%

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

[0021]

[Table 2] ────────────────────────── Formulation amount (% by weight) Effect ────────── ──────────────── No addition-× Hydroquinone 1.0 △ Curen extract 0.1 ○ Curen extract 1.0 ○ Curen extract 10.0 ◎ ──── ──────────────────────

The Curen extract shown in Table 2 is obtained by reducing the whole plant of Curen by heating in ethanol, filtering, concentrating and drying.

As is evident from Table 2, the effect after exposure to sunlight was confirmed by adding the curen extract to prevent the deposition of excessive melanin pigment and prevent the color from becoming black. Was.

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 Curen methanol extract 0.01 Caustic potash 0.2 Sodium bisulfite 0.01 Preservatives Appropriate amount Fragrance Appropriate amount Ion-exchanged water Residue (Preparation method) Add propylene glycol, curen methanol extract and caustic potash to ion-exchanged water, dissolve and heat to 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 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 Curen ethanol extract 0.05 Sodium bisulfite 0.03 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water Residue (Production method) Propylene glycol for ion-exchanged 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 Curen acetone extract 0.05 Curen ethanol extract 0.05 Sodium bisulfite 0.03 Ethyl paraben 0.3 Perfume Appropriate amount Ion exchange water Residue (Production method) Ion exchange water Soap powder and borax are added to the mixture, and the mixture is dissolved by heating and maintained 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) 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 0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (Product name: Carbopol 941, BFGoodrich Chemical company) Curenic acid ethyl ester extract 0.01 Sodium bisulfite 0.01 Ethyl paraben 0.3 Fragrance Appropriate amount Ion exchange water Residue (Preparation method) Dissolve the carboxyvinyl polymer 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 carry out preliminary emulsification, the phase A is added, and the mixture is uniformly emulsified with a homomixer.

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 Curenacetone extract 10.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion exchange water residue (Preparation method) Add propylene glycol to ion exchange 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 (trade name: Carbopol) 940, BFGoodrich Chemical company) Caustic soda 0.15 L-arginine 0.1 Curen 50% ethanol aqueous solution extract 7.0 Sodium 2-hydroxy-4-methoxybenzophenonesulfonate 0.05 Ethylenediaminetetraacetate trisodium 2 water 0 .05 Methyl paraben 0.2 Perfume Appropriate amount Ion-exchanged water Residue (Preparation method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while 95% ethanol is a 50% aqueous solution of curen in 50% ethanol, polyoxyethylene (50 mol) oleyl Alcow Was dissolved 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 Essence (Formulation) (Phase A) Ethyl alcohol (95%) 10.0% by weight Polyoxyethylene (20 mol) octyldodecanol 1.0 Pantothenyl ethyl ether 0.1 Curen 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) (Phase A) Dipropylene glycol 5.0 wt% Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Curen methanol extract 0.01 Olive oil 5. 0 Tocopherol acetate 0.2 Ethyl paraben 0.2 Fragrance 0.2 (C phase) Sodium bisulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, Polymerization degree 2,000) Ethanol 7.0 Purified water Residue ( Production method) A phase, B phase, and C phase are each dissolved uniformly,
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 2.0 Isostearic acid 4.0 POE sorbitan monooleate 3.0 Isocetyl octoate 2.0 Curen ethanol 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 curen 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 cu Lenethanol 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.

[0034]

As described above, the external preparation for skin of the present invention has an inhibitory action on melanin production and an inhibitory action on tyrosinase activity, and reduces the coloration of pigmentation, spots, freckles, liver spots, etc. after sunburn. It is an external preparation for skin that has excellent whitening effect and safety.

──────────────────────────────────────────────────の Continued on the front page (72) Inventor Hisayuki Komazaki 1050 Nippa-cho, Kohoku-ku, Yokohama, Kanagawa Prefecture Inside Shiseido First Research Center Co., Ltd. (72) Masako Naganuma 1050 Nippa-cho, Kohoku-ku, Yokohama, Kanagawa Stock (72) Inventor Minoru Fukuda 1050 Nippa-cho, Kohoku-ku, Yokohama, Kanagawa Prefecture Shiseido First Research Center (56) References JP-A-6-128143 (JP, A) JP-A-6-128142 (JP, A) JP-A-6-128145 (JP, A) JP-A-6-199646 (JP, A) JP-A-6-87731 (JP, A) (58) Fields investigated (Int) .Cl. ⁷ , DB name) A61K 7/48 A61K 7/00 A61K 35/78 CA (STN)

Claims (3)

(57) [Claims] 1. Curen (scientific name: Psoralea)
A topical skin preparation comprising an extract of mexicana vail). 2. The amount of the curen extract is 0.005.
The external preparation for skin according to claim 1, wherein the amount is from 2 to 20.0% by weight. 3. The external preparation for skin according to claim 1, which is an external preparation for skin whitening.