JPH0812561A - Beautifying and whitening skin preparation for external use - Google Patents

Abstract

PURPOSE:To obtain the subject preparation for external use, having suppressing actions on melanogenesis and inhibiting actions on tyrosinase activities, excellent in lightening of the color, beautifying and whitening of pigmentation, dermal stains, ephelides, chloasmata, etc., after sunburn, excellent in safety and useful as an ointment, a cream, etc., by blending an extract of Arnica therein. CONSTITUTION:This skin preparation for external use is obtained by blending 0.005-20.0wt.%, preferably 0.01-10.0wt.% extract of Arnica (botanical name: Senecio Canescens Cuatr). Furthermore, the Arnica is a plant growing in an arid grassland, a pasture, etc., in South America, especially the Andes, etc. For example, an extract prepared by immersing a leaf and a stem or a fruit, etc., of the Arnica or the whole herb thereof in an extracting solvent such as ethanol or refluxing the solvent together with the leaf, etc., therein under heating, filtering the resultant extract solution, concentrating the prepared filtrate, etc., is preferably used as the extract.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to Arnic
The present invention relates to a skin external preparation for whitening, which is effective in inhibiting the production of melanin by blending the extract of a) and preventing and improving pigmentation, spots, freckles, chloasma and the like after sunburn.

[0002]

BACKGROUND OF THE INVENTION Although there are some unclear points about the mechanism of skin spots and the like, in general, melanin pigments are formed due to hormonal abnormalities and irritation of ultraviolet rays from the sun, and this is the skin. It is thought to be abnormally deposited inside. 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, the process in which tyrosine, which is an essential amino acid, becomes dopaquinone by the action of the enzyme tyrosinase, and this is converted to black melanin via the red and colorless pigments by the enzymatic or non-enzymatic oxidation action is the melanin pigment formation 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]

The inventors of the present invention investigated the melanin production inhibitory effect of various substances as a solution to these problems, and found that Arnica (Arn
It was found that the extract of ica, scientific name: Senecio Canescens Cuatr) has a melanin production inhibitory action and a tyrosinase inhibitory action, and has completed the present invention.
There has been no report on the melanin production inhibitory action of Arnica extract, and its application to a whitening agent has not been known at all. The present inventors have completed the present invention based on the above findings.

That is, the present invention is based on Arnic
a, Scientific name: Senecio Canescens Cuatr) is an external preparation for whitening skin, which is characterized by being blended.

The structure of the present invention will be described in detail below. Arnica used in the present invention is a plant that grows in South America, especially in dry grasslands such as the Andes, grasses and the like. The extract used in the present invention is obtained by immersing or heating and refluxing whole Arnica grass such as leaves, stems or fruits as described above, filtering and concentrating. The extraction solvent used in the present invention may be any solvent that is usually used for extraction, and in particular, alcohols such as methanol and ethanol, hydrous alcohols, acetone, and organic solvents such as acetic acid ethyl ester may be used alone or in combination. You can

The blending amount of the arnica extract in the present invention is 0.005 to 20.0 as a dry product in the total amount of the external preparation.
%, Preferably 0.01-10.0% by weight.
If it is less than 0.005% 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 it is blended in an amount of 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 added.

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. The present invention is not limited to this. The blending 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 50 g of Arnica stem and branch portion,
It was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 5.2 g of ethanol extract. DMSO
1%, and the solution was diluted to adjust the concentration, and the following experiment was conducted using the solution.

2. Cell Culture Method B16 melanoma cultured cells derived from mouse 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 measurement of melanin amount A diffuser plate was placed on the lid of the plate of the well, the intracellular melanin amount was observed with an inverted microscope, and compared with the case of the sample (reference) to which the Arnica extract was not added. 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. The results are also shown in Table 1. Also in the table,
Toxicity 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 the measurement, the medium in the wells is removed, and the wells are 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 inhibition rate (%) was defined as the decrease in the absorbance difference of the sample added with the arnica extract relative to the absorbance difference at 0 minutes and 60 minutes in the case where the sample (control) to which the arnica extract was not added. 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. The results are also shown in Table 1. 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.

[0017]

[Table 1] ─────────────────────────────────── Test Melanin production Visual evaluation Tyrosinase activity inhibition rate ( %) ──────── ──────────────────────── concentration (wt%) 10 ^-5 10 ^-4 10 ^-3 10 ^{- 2} 10 ^-5 10 ^-4 10 ^-3 10 ^-2 ─────────────────────────────────── Arnica extraction Substance × × △ Toxicity 27 33 52 Toxicity Kaigai 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 rate of marked efficacy and efficacy among subjects is 80% or more ◯: The rate of marked efficacy and efficacy among subjects is 50% to
In the case of less than 80% Δ: Remarkable and effective proportion of subjects is 30% to
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.

[0021]

[Table 2] ────────────────────────── Drug compounding amount (% by weight) Effect ────────── ──────────────── Additive- × Hydroquinone 1.0 △ Arnica extract 0.1 ○ Arnica extract 1.0 ○ Arnica extract 10.0 ◎ ──── ──────────────────────

The Arnica extracts shown in Table 2 are obtained by heating and reducing whole plants of Arnica in ethanol, filtering and concentrating and drying.

As is clear from Table 2, the effect after exposure to sunlight was found to be that the addition of the arnica extract prevents excessive melanin pigment deposition and prevents darkening. It was

Example 1 Cream (prescription) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Arnicamethanol extract 0.01 Caustic potash 0 .2 Sodium hydrogen sulfite 0.01 Preservative proper amount Perfume proper amount Ion-exchanged water Residue (production method) Propylene glycol, arnica methanol extract and caustic potash are added to ion-exchanged water and dissolved, and heated to 70 ° C (water phase). The other ingredients are mixed, heated and melted and maintained 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 the 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 Arnica ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume proper amount Ion exchange water Residue (production method) Propylene glycol is added to ion exchange water In addition,
Heat to maintain 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained 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 soap powder 0.1 borax 0.2 arnica acetone extract 0.05 arnica ethanol extract 0.05 sodium bisulfite 0.03 ethylparaben 0.3 perfume suitable amount ion-exchanged water residual (manufacturing method) soap in ion-exchanged water The powder and borax are added, melted by heating and kept at 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is stirred into the water phase and gradually added 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 (trade name: Carbopol 941, BFGoodrich Chemical company) Arnica acetic acid ethyl ester extract 0.01 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Perfume proper amount Ion exchange water Residual (manufacturing method) The carboxyvinyl polymer is dissolved in a small amount of ion-exchanged water (phase A). Polyethylene glycol 1500 and triethanolamine were added to the remaining ion-exchanged water, and the mixture was heated and dissolved and maintained at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase for preliminary emulsification, the phase A is added and the mixture is homogenized with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. while being well stirred.

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 Arnicaacetone extract 10.0 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water Residue (production method) Add propylene glycol to ion-exchanged water,
Heat to maintain 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added to this and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C while stirring well.

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 Arnica 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 Fragrance Appropriate amount Ion-exchanged water Residual (production method) Carbopol 940 was uniformly dissolved in ion-exchanged water, while Arnica 50% ethanol aqueous solution extract and polyoxyethylene (50 mol) oleyl was added to 95% ethanol. Arcor 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 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Weight Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Arnica Methanol 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 phase and solubilize. Next, phase B is added and then 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) Arnica methanol extract 0.01 Olive oil 5.0 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 Residual (manufacturing method ) A phase, B phase, and C phase are uniformly dissolved,
Phase B is added to the phase to solubilize it. Next, this is added to phase C 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 octanoate 2.0 arnica ethanol extract 1.0 preservative appropriate amount perfume appropriate amount (manufacturing method) Talc-black iron oxide powder components are thoroughly mixed with a blender. Then, an oily component of squalane to isocetyl octoate, an arnica 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% 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 (water phase) purified water 50.0 1,3-butylene glycol 4.5 Arnica Ethanol extract 1.5 Sorbitan sesquioleate ester 3.0 Preservative proper amount Perfume proper amount (Production method) After heating and stirring the aqueous phase, the powder portion thoroughly mixed and pulverized is added and subjected to a homomixer treatment. Further, the heated and mixed oil phase is added and subjected to a homomixer treatment, and then a fragrance is added with stirring and cooled to room temperature.

[0034]

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 is an external preparation for whitening skin, which has excellent effects on lightening and whitening, and is also excellent in safety.

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

Claims (2)

[Claims] 1. Arnica (scientific name: Seneci)
o Whitening skin external preparation characterized by containing an extract of Canescens Cuatr). 2. The blending amount of Arnica extract is 0.005.
The external preparation for whitening skin according to claim 1, which is ˜20.0 wt%.