JPH11246344A - Preparation for external use for skin bleaching - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation for external use which can exert excellent melanin formation controlling effect and tyrosinase inhibitory effect and possesses high safety by blending an extract from leguminous plants. SOLUTION: This preparation for external use is obtained by blending an extract from the plant of the family Fabaceae the genus Gliricidia [preferably Cocohuite (botanical name: Gliricidia sepium)]. The extract used can be obtained by immersing or refluxing branches, roots or leaves of the above plant or the whole part of the plant together with an extraction solvent (preferably alcohols, hydrous alcohols or acetone) followed by filtration and concentration. Further, the extract is preferably blended in an amount of 0.0005-10.0 wt.% based on the whole weight of the preparation for external use in the dry basis. By this process, the excellent effect is expectable in the lightening in color of pigmentation after getting sunburned, stain or freckle and the skin bleaching.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a legume (Fabaceae)
The present invention relates to a skin whitening preparation for external use which is effective for preventing and improving pigmentation, spots, freckles, melasma and the like after sunburn by adding an extract of a plant of the genus Gliricidia.

[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.

[0003] This melanin pigment, which causes coloring of the skin, is produced in melanin-producing granules (melanosomes) in melanocytes (melanocytes) between the epidermis and the dermis. Spread to 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, which is converted into black melanin via a red pigment and a colorless pigment by an enzymatic or non-enzymatic oxidative action in the process of producing melanin pigment. is there.

[0005] Therefore, suppressing the action of tyrosinase, which is the first step of the reaction, is important for suppressing the production of melanin.

[0006]

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.

[0007] On the other hand, although hydroquinone has been 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. For this reason, it is not always safe, and ethers have not been obtained that are sufficiently satisfactory in terms of safety.

As a solution to these problems, the present inventors have conducted extensive studies on the effect of inhibiting melanin production on a wide variety of substances. As a result, an extract of a plant belonging to the genus Fabaceae or Gliricidia was found to produce melanin. They have found that they have an inhibitory action and a tyrosinase inhibitory action, and have completed the present invention.

An object of the present invention is to provide a highly safe skin whitening external preparation having an excellent melanin production inhibitory action and a tyrosinase inhibitory action.

[0010]

That is, the present invention provides a skin whitening preparation for external use characterized by containing an extract of a plant of the genus Fabaceae Gliricidia.

The present invention also relates to a plant of the genus Fabaceae belonging to the genus Gliricidia.
huite, scientific name: Gliricidia sepium).

Furthermore, the present invention relates to the above-mentioned Fabaceae.
The amount of the extract of the plant belonging to the genus Gliricidia is 0.0005 to 1 with respect to the total amount of the external preparation for whitening skin.
0.03% by weight of the skin whitening agent for external use.

[0013]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The configuration of the present invention will be described below in detail.

The plants of the genus Fabaceae Gliricidia used in the present invention include coco huite (Co
cohuite, scientific name: Gliricidia sepium) is preferred,
Grilisilia (scientific name: Gliricidia kunph) is also effective and is not limited to Cocohuite. Coco Huite is a plant that grows especially on dry grasslands and pastures in Mexico.

The Fabaceae family Glirici
dia) The melanin production inhibitory action and the tyrosinase inhibitory action of the extract of the genus plant are the effects discovered for the first time by the present inventors, and are completely known not only for application to whitening agents but also for external application to skin. Not.

[0016] The extract used in the present invention comprises the following:
Stems including roots, leaves, rhizomes, fruits, flowers, etc., or whole plants are soaked or heated under reflux with an extraction solvent, and then filtered and concentrated. The extraction solvent is not particularly limited as long as it is a solvent usually used for extraction.For example, organic solvents such as alcohols such as methanol and ethanol, hydroalcohols, acetone, and ethyl acetate are used alone or in combination. Is preferred.

The Fabaceae family Glirici
dia) The amount of the extract of the genus plant is 0.0005 to 10.0% by weight as a dry matter in the total amount of the external preparation, preferably,
0.001 to 5.0% by weight. 0.0005% by weight
If less than, the effect of the present invention is not sufficiently exhibited,
If it exceeds 10.0% by weight, it is difficult to formulate the composition, which is not preferable. Further, even if the content is 5.0% by weight or more, the effect is not so greatly improved.

In addition to the above essential components, the skin whitening preparation of the present invention contains, in addition to the above essential ingredients, components usually used in skin external preparations such as cosmetics and pharmaceuticals, for example, other whitening agents, humectants, 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.

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.

[0020]

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 of the melanin inhibitory effect, tyrosinase activity inhibitory effect, and whitening effect of the plant extract used in the present invention will be described.

"Test method and its results" Preparation of sample Cocohuite (scientific name: Gliricidia sepium)
Was immersed in ethanol at room temperature for one week, and the extract was concentrated to obtain 1.9 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 culturing, the sample solution is added to a final concentration (concentration in terms of dry extract) of 10 ^-2 to 10 ^-4 % by weight, and the culturing is continued for further 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 confirm the Gliridia
This was compared with the case of a sample (reference) to which no extract of the genus cidia) was added. The results are shown in "Table 1" according to the following criteria. 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. The results are shown in Table 1 together.

<Judgment Criteria> A: White compared to the standard (melanin content is smaller than the standard) C: Slightly white compared to the standard (melanin content is slightly smaller than the standard) C: Standard Comparable

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). The results are shown in Table 1. 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. The results are shown in Table 1 together. In the table,-
Means that no significant difference was observed within 5% of the risk compared to the control.

[0026]

[Table 1]--------------------------------------------------] ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ----------------------------------------------------------------- --- --- --- Concentration (% by weight) 10 ^-4 10 ^-3 10 ^-2 10 ^-4 10 ^-3 10 ^-2 ----------------------------------------------------------------- --- Coco huite extract × ○ ○ 92 73 0 -------------------------------------- ------------------------------ー ー ー ー ー ー ー Kakei extract × × × − − 55 -------------------------------------------------------

5. [Whitening effect test] [Test method] The day when 40 subjects were exposed to sunlight with artificial light (UV-A + UV-B) for 30 minutes (10 minutes a day for 3 days). After 5 days, each sample was applied once in the morning and evening for 4 weeks. The panel was divided into eight groups and divided into five groups, and a test was performed using a skin external preparation having 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 (described in “Table 2”) “Table 2” (Aqueous phase) Glycerin 5.0 Sodium hexametaphosphate Appropriate amount Ion-exchanged water Residue <Production method> Prepare an aqueous phase and an alcohol phase, 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%

Using the agents listed in Table 2, skin whitening external preparations having the above composition were prepared, and the whitening effects were compared. The results are shown in "Table 2".

[0031]

[Table 2]-----------------------------------------------------] ----------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------ ----------------------------------------------------------------- ----- Hydroquinone 1.0 △ ー ー ー ー ー ー ー ー ー ハ イ ド ロ ハ イ ド ロ ハ イ ド ロ ハ イ ド ロ ハ イ ド ロ ハ イ ド ロ ハ イ ド ロ キ ハ イ ド ロ キ キ---------------------------------------------------------------------------------------------------------------------------------------------------- -------------- Coconut extract 1.0 ------------------------- Coconut extract 5-4.--------------------------------------- 0 ◎ ー ー ー ー ー ー ー ー ◎ ◎ ◎ ◎ ◎ ◎ ◎ --------------

The extract of Coco Huite shown in Table 2 was
It is obtained by reducing the branches of Kokohuite by heating in ethanol, filtering, concentrating and drying.

As is clear from Table 2, the effect after exposure to sunlight is that the addition of Kokohuite extract can prevent the deposition of excessive melanin pigment and prevent blackening. Admitted.

Examples of the skin whitening agent for external use of the present invention are shown below. The Kokohuite and Grilisilia extracts are obtained by reducing the branches by heating in each extraction solvent, filtering, concentrating and drying.

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 Coco extract methanol extract 0.01 Caustic potash 0.2 Preservatives Appropriate amount Fragrance Appropriate amount Ion-exchanged water Residue (Preparation method) Add propylene glycol, coconut 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). 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. 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 Coco huite ethanol extract 0.05 Ethyl paraben 0.3 Appropriate amount of ion-exchanged water Residue (Production method) Add propylene glycol to ion-exchanged water,
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 2.0 Soap powder 0.1 2-Ethylhexyl paramethoxycinnamate 1.5 Borax 0.2 Coco huite acetone extract 0.05 Ascorbic acid 2 glucoside 2.0 Coco huite ethanol extract 0.05 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water Residue (Preparation method) Add soap powder and borax to ion-exchanged water, dissolve by heating 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) 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 (trade name: Carbopol 941, BFGoodrich Chemical company) Grilisia 30% ethanol extract 1.5 Placental extract 1.0 Ethylparaben 0.3 Perfume Appropriate amount ion-exchanged 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, pre-emulsification is performed, 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 Coco huite acetone extract 5.0 Kojic acid 1.0 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 (Product name: Carbopol) 940, BFGoodrich Chemical company) Caustic soda 0.15 L-arginine 0.1 Cocohite 50% ethanol extract 1.5 Sodium 2-hydroxy-4-methoxybenzophenonesulfonate 0.05 Ethylenediaminetetraacetate trisodium 2 water 0. 05 Methylparaben 0.2 Perfume Appropriate amount Ion-exchanged water Residue (Preparation method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while Cocohite 50% ethanol aqueous solution extract in 95% ethanol, polyoxyethylene (50 mol) oleyl alcohol Was dissolved over ether, is added to the aqueous phase. Then, after adding other components, caustic soda,
Neutralize with L-arginine to thicken.

Example 7 Essence (Prescription) (A phase) Ethyl alcohol (95%) 10.0% by weight Polyoxyethylene (20 mol) octyldodecanol 1.0 Pantothenyl ethyl ether 0.1 Cocohuteine methanol Extract 1.5 Ascorbic acid glucoside 1.5 Arbutin 3.0 Methyl paraben 0.15 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxy Vinyl polymer 0.2 (trade 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% by weight Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Coco Huite methanol extract 0.01 Olive oil 5 2.0 Tocopherol acetate 0.2 Ethyl paraben 0.2 Perfume 0.2 (C phase) Ascorbic acid 2 glucoside 2.0 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 wt% 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 Coco huite ethanol extract 1.0 Preservatives Appropriate amount Fragrance Appropriate amount (Production method) Powdery components of talc to black iron oxide are sufficiently blended. Mix and add the oily components of squalane to isocetyl octanoate, coco huite ethanol extract, preservative,
After adding fragrance and kneading well, 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 Coco Huite 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, and a homomixer treatment is performed. 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.

[0045]

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 Nippa-cho, Kohoku-ku, Yokohama-shi, Kanagawa Inside Shiseido Daiichi Research Center Co., Ltd.

Claims (3)

[Claims] The present invention relates to a family of legumes (Fabaceae) Gliri.
An external preparation for skin whitening, comprising an extract of a genus cidia). 2. The legume family (Fabaceae) glirisidia (G
liricidia) plant is Cocohuite (scientific name: Gl
2. The skin whitening agent for external use according to claim 1, which is iricidia sepium). 3. The legume family (Fabaceae) glirisidia (G
The skin whitening agent according to claim 1 or 2, wherein the amount of the extract of the liricidia genus plant is 0.0005 to 10.0% by weight based on the total amount of the skin whitening agent.