JPH0920634A - 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 an extract of Cinnamomum verum or Cinnamomum sintoc Bl. belonging to the genes Cinnamomum of the family Laurace, especially which grows in the 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, etc., can properly be blended in the skin preparation for external use and the skin preparation can be prepared in ointment, cream, lotion, 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]

BACKGROUND OF THE INVENTION The present invention relates to a specific Laurac tree.
eae) Cinnamomum genus plant extract is contained to suppress the production of melanin and is effective for preventing and improving pigmentation, spots, freckles, chloasma, etc. 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]

[Means for Solving the Problems] Therefore, as a result of investigating the melanin production inhibitory effect of a wide variety of substances for solving these problems, the present inventors found that a specific plant of the genus Cinnamomum of the Lauraceae family. 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. Lauraceae family cinnamomum (Cinna
For the report on the melanin production inhibitory effect of the extract of the genus momum), Japanese Patent Laid-Open No. 63-40403 has disclosed that Keihin tincture obtained from Cinnamomum cassia Blume as a raw material was incorporated into an external preparation as a melanin production inhibitor. The plant is known, but other plants are not known at all.

That is, the present invention is based on Lauracea.
e) Manis jangan of the genus Cinnamomum (scientific name: Cinnamomum ve
rum) or Sintok (scientific name: Cinnamomu)
It is an external preparation for whitening skin, which is characterized by containing an extract of m sintoc Bl.).

The structure of the present invention will be described in detail below. Manis j used in the present invention
angan, scientific name: Cinnamomum verum) and Sintok, scientific name: Cinnamomum sintoc Bl.
In particular, it is a plant that grows on Indonesian dry grasslands and pastures. The extract used in the present invention is obtained by immersing or heating and refluxing whole plants such as leaves of plants, stems including rhizomes, bark, fruits and the like with an extraction solvent, followed by filtration and concentration. The extraction solvent used in the present invention may be any solvent as long as it is a solvent usually used for extraction, in particular, alcohols such as methanol and ethanol, hydrous alcohols, acetone,
Organic solvents such as ethyl acetate can be used alone or in combination.

In the present invention, the manis jangan (Ma)
Nis Yang, Scientific name: Cinnamomum verum) and Sintok, Scientific name: Cinnamomum sintoc
The compounding amount of the Bl.) Extract is 0.005 to 20.0% by weight, preferably 0.01 to
It is 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.

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) Manis jangan
Extract liquid 50 g of a bark portion of Manis jangan was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 4.2 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) Sintok extract 50 g of the bark of Sintok was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 1.5 g of an ethanol extract. 1% of this extract in DMSO
After dissolution, this solution was diluted to adjust the concentration, and the following experiment was conducted 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 and observe the intracellular melanin amount with an inverted microscope.
e) Comparison was made with the sample (reference) to which the extract of the genus Cinnamomum was not added. The results are shown in Table 1. In addition, as a reference example, a cabbage extract (Cinnamomum c.), Which is already known to have an action of suppressing melanin production, and Cinnamomum c.
The same test as described above was performed for the assiaBlume) extract. Table 1 also shows the results. Further, in the table, "toxic" means that it is cytotoxic.

<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. In addition, as a reference example, an ethanol extract of cinnamon and Cinnamomum cassia Blume, which is already known to have a tyrosinase activity inhibitory action,
The same test as above was performed for the ethanol extract of. 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.

[0018]

[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 ──────────────────────────────────── Manis ・Jangan extract × ○ Toxic toxicity 86 57 Toxic toxicity Toxic extract X × × ○ − − − − 30 Keigai extract × × × × − − − 55 Keihi extract × × × △ − − − − 45 ─────── ──────────────────────────────

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.

[0022]

[Table 2] ────────────────────────── Drug compounding amount (% by weight) Effect ────────── ──────────────── Additive- × Hydroquinone 1.0 △ Manis jangan extract 0.1 ○ Manis jangan extract 1.0 ○ Manis jangan extract 10. 0 ◎ Sintok extract 0.1 ○ Sintok extract 1.0 ○ Sintok extract 10.0 ◎ ───────────────────────────

The Manis jangan extract and the mint extract in Table 2 were obtained by heating and reducing the bark 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 Manis jangan extract or the Shintoku extract prevented excessive melanin pigment deposition,
It was found to 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 Manis jangan methanol extract 0. 01 Caustic potash 0.2 Sodium bisulfite 0.01 Preservative Suitable amount Perfume Suitable amount Ion-exchanged water Residual (production method) Dissolve propylene glycol, Manis Jungan methanol extract and caustic potash in ion-exchanged water and heat to 70 ° C Keep (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 water phase, and after the addition is completed, 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 Sintok ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume suitable amount Ion-exchanged water Residue (production method) Propylene glycol is added to ion-exchanged water In addition,
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 wt% 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 Manis janganacetone extract 0.05 Sintoku ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water Residual (process) Ion-exchange Soap powder and borax are added to 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 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 wt% 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) Manis jangan acetic acid ethyl ester extract 0.01 Sodium bisulfite 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 wt% Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 moles) ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Sintokacetone extract 10.0 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Perfume suitable amount Ion-exchanged water Residue (production method) Propylene glycol is added 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 (trade name: Carbopol 940, BFGoodrich Chemical company) Caustic soda 0.15 L-arginine 0.1 Manis jangan 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sulfonate sodium 0.05 Ethylenediaminetetraacetate-3 sodium-2 Water 0.05 Methylparaben 0.2 Perfume Appropriate amount Ion-exchanged water Residue (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while Manis-Jean-Gan 5 in 95% ethanol
0% aqueous ethanol extract, polyoxyethylene (5
0 mol) oleyl alcohol ether is dissolved and 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 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Weight Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Sintokumethanol Extract 1.5 Methylparaben 0.15 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 (trade name: Carbopol 940 , BFGoodrich Chemical company) Purified water Residual (manufacturing method) A phase and C phase are uniformly dissolved, and A is added 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) Manis jangan methanol extract 0.01 Olive oil 5.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Perfume 0.2 (C phase) Sodium hydrogen sulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, degree of polymerization 2,000) Ethanol 7.0 Purified water Residual (manufacturing method) Phases A, B, and 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 Sintok ethanol extract 1.0 Preservative proper amount Fragrance appropriate amount (manufacturing process) Talc to black iron oxide powder components are thoroughly mixed with a blender. Then, an oily component of squalane to isocetyl octoate, a syntoque ethanol extract, an antiseptic and a fragrance are added, and the mixture is well kneaded and then filled into a container and molded.

Example 10 Emulsion type foundation (cream type) (Formulation) (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 (Aqueous phase) Purified water 50.0 1,3-Butylene glycol 4.5 Manis -Jangan ethanol extract 1.5 sorbitan sesquioleate 3.0 preservative proper amount perfume proper amount (manufacturing method) After heating and stirring the aqueous phase, the 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.

[0035]

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. Manis jangan of the genus Cinnamomum of the Lauraceae family.
An external preparation for whitening skin, comprising an extract of jangan, scientific name: Cinnamomum verum) or sintoku (scientific name: Cinnamomum sintoc Bl.). 2. Manis jagan
Ngan, scientific name: Cinnamomum verum) or Sintok (scientific name: Cinnamomum sintoc Bl.) extract is blended in an amount of 0.005 to 20.0% by weight.