JPH0930950A - Beautifying and whitening dermal preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a beautifying and whitening dermal preparation for external use, having suppressing actions on melanogenesis and inhibiting actions on tyrosinase activities and effective in preventing and reducing pigmentation, dermal stains, ephelides, chloasma, etc., after the sunburn. SOLUTION: This beautifying and whitening dermal preparation for external use contains 0.005-20wt.%, preferably 0.01-10wt.% extract of a plant, growing in especially a dry grassland, a stock farm, etc., of Indonesia and belonging to the genus Tinospora of the family Menispermaceae, preferably Brotowali (botanical name: Tinospora tuberculata Beumee) as an essential ingredient therein. The extract, as necessary, is suitably further blended with a beautifying and whitening agent, a humectant, an antioxidant, an oily ingredient, an ultraviolet absorber, a surfactant, a thickening agent, alcohols, a powdery ingredient, a colorant, an aqueous ingredient, water, various dermal nutrients, etc., and prepared into an ointment, a cream, a milky lotion, a lotion, a pack, a bathing agent, etc. Furthermore, the extract is obtained by immersing or refluxing a leaf, a stem, a fruit, etc., of the plant, the whole herb, etc., thereof together with an extracting solvent (e.g. ethanol) under heating, then filtering the resultant extract and concentrating the prepared filtrate.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is directed to the azalea (Menisperma)
ceae) A whitening skin external preparation that is effective in preventing and improving pigmentation, stains, freckles, chloasma, etc. after sunburn by suppressing the formation of melanin by incorporating an extract of the genus Tinospora 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]

The inventors of the present invention investigated the melanin production inhibitory effect on various substances as a solution to these problems, and found that the tsutsurafuji (Meni
The present inventors have found that an extract of a plant of the genus Tinospora of the spermaceae family has a melanin production inhibitory action and a tyrosinase inhibitory action, and completed the present invention. Chinospora (Tinos) (Menispermaceae)
There have been no reports of melanin production inhibitory effects of extracts of plants belonging to the genus pora), and their application to whitening agents has not been known. The present inventors have completed the present invention based on the above findings.

That is, the present invention is directed to Menisper
Maceae) A skin external preparation for whitening, comprising an extract of a plant of the genus Tinospora.

The structure of the present invention will be described in detail below. The plant of the genus Tinospora of the family Menispermaceae used in the present invention is Brotowari (Br
Otowali, scientific name: Tinospora tuberculata Beume
e) is preferred. This is a plant that grows especially on dry grasslands, pastures and the like in Indonesia. The extract used in the present invention is obtained by immersing or heating and refluxing the above-mentioned plant leaves, stems including rhizomes, fruits, whole plants, etc., 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.

[0007] In the present invention, Menispermace
ae) The compounding amount of the extract of the genus Tinospora is 0.005 to 20.0 as a dried product in the total amount of the external preparation.
%, Preferably 0.01-10.0% 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 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 (1) Brotowari (scientific name: Tinospor
a tuberculata Beumee) Extract Brothowali (scientific name: Tinospora tu)
50 g of berculata Beumee) tubers were immersed in methanol at room temperature for 9 days, and the extract was concentrated to obtain 1.04 g of a methanol 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.sub.2 in a CO.sub.2 incubator (95% air, 5% carbon dioxide) at 37.degree. After 24 hours of culturing, the sample solution was added so that the final concentration (concentration of extracted dry matter) was 10 −2 to 10 −5% by weight, and the culturing was continued for another 3 days. The determination and the tyrosinase activity inhibitory effect were measured.

3. Visual measurement of the amount of melanin Place a diffusion plate on the lid of the well plate, observe the intracellular amount of melanin with an inverted microscope, and
owali, scientific name: Tinospora tuberculata Beumee) was compared with the case of a sample (standard) to which an extract was not added. The results are shown in Table 1. Also, as a reference example,
The same test as described above was carried out also on an extract of mussel (Lamiaceae, Odorikosou subfamily), which is already known to have a melanin production inhibitory action. 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.

[0017]

[Table 1]

Test Melanin production Visual evaluation Tyrosinase activity rate (%) Concentration (wt%) 10-5 10-4 10-3 10-2 10-5 10-4 10-3 10-2 Broccoli extract △ △ △ ○ 81 83 62 35 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 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]

The broccoli extract in Table 2 was obtained by heating and reducing the tubers of plants in methanol, filtering and concentrating and drying.

As is clear from Table 2, the effect after exposure to sunlight was found to be that addition of the extract of Broccoli prevents excess melanin pigment deposition and prevents darkening. Was given.

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 Brotowari 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, Brotowari methanol extract and caustic potash in ion-exchanged water and heat to maintain 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 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 ester 2.0 Propylene glycol 5.0 Brothwari ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume suitable amount Ion-exchanged water Residue (production method) Propylene glycol in 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 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 soap powder 0.1 borax 0.2 brothwarriacetone extract 0.1 sodium bisulfite 0.03 ethylparaben 0.3 fragrance suitable amount ion-exchanged water residual (manufacturing method) Add soap powder and borax to ion-exchanged water, Melt by heating and keep 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) Brotowari acetic acid ethyl ester extract 0.01 Sodium bisulfite 0.01 Ethylparaben 0.3 Perfume Suitable amount Ion-exchanged water Residual (manufacturing method) The 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 Brotowariacetone extract 10.0 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Perfume suitable amount Ion-exchanged water Residual (production method) Add propylene glycol 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 Brothwari 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenonesulfonic acid sodium salt 0.05 Ethylenediaminetetraacetate / 3sodium / dihydrate 0 .05 Methylparaben 0.2 Fragrance Suitable amount Ion-exchanged water Residue (production method) Carbopol 940 was uniformly dissolved in ion-exchanged water, while Brotowari 50% ethanol aqueous solution extract and polyoxyethylene (50 mol) in 95% ethanol.
Dissolve the oleyl alcohol ether and add to the aqueous phase. Then, after adding other components, caustic soda, L
-Neutralize with arginine to thicken.

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 0.1 Brothwarri Methanol Extraction Substance 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 Residue (production 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 (prescription) (Phase A) Dipropylene glycol 5.0 wt% Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Broccoli 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, respectively.
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 Brothwarri ethanol extract 1.0 Preservative proper amount perfume proper amount (manufacturing process) Talc-black iron oxide powder components are thoroughly mixed with a blender. Then, an oily component of squalane to isocetyl octanoate, a brothwari ethanol extract, a preservative, and a fragrance are added thereto, 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 (water phase) purified water 50.0 1,3-butylene glycol 4.5 bro Thoi ethanol extract 1.5 sorbitan sesquioleate 3.0 preservative proper amount perfume proper amount (manufacturing method) The aqueous phase is heated and stirred, and then the powder portion thoroughly mixed and pulverized is added to perform 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.

[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.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Hirohiko Sakamoto 1050 Nippa-cho, Kohoku-ku, Yokohama-shi, Kanagawa Inside Shiseido Daiichi Research Center Co., Ltd.

Claims (3)

[Claims] 1. An external preparation for whitening skin, comprising an extract of a plant of the genus Tinospora of the family Menispermaceae. 2. A plant of the genus Tinospora of the family Menispermaceae is Brotowa.
Li, scientific name: Tinospora tuberculata Beumee), The external preparation for whitening skin according to claim 1. 3. The compounding amount of the extract of the genus Tinospora belonging to the family Menispermaceae of 0.005 is 0.005.
The skin external preparation for whitening according to claim 1 or 2, which is ˜20.0% by weight.