JPH0987197A - Tyrosinase inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a tyrosinase inhibitor having tyrosinase activity inhibitory effect and effective for preventing and remedying pigmentation, spots/freckles and chloasma, etc., subject to development after suntan. SOLUTION: This tyrosinase inhibitor contains an extract from Secant, Caddying, Daunsogo, Kembangmelati, Tempuyung, Orangaring, Kemukus, Kayuputih, Tumbar, Bendo, Dauntrawas, Belantas, Cabejawa, Widoroupas, Botor, Kayurapet, or Kecibeling.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a tyrosinase inhibitor having a tyrosinase activity inhibitory effect which is effective in preventing and improving pigmentation, spots, freckles, liver spots, etc. after sunburn by adding an extract of a specific plant. Agent.

[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, 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. Therefore, it is important to suppress the action of tyrosinase, which is the first step of the reaction, to suppress melanin production.

[0004]

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.

[0005]

As a result of investigating the tyrosinase activity inhibitory effect of various substances as a solution to these problems, the inventors of the present invention have found that a specific plant extract has a tyrosinase activity inhibitory effect. The present invention has been completed and the present invention has been completed. There has been no report on the tyrosinase activity inhibitory activity of these plant extracts described below, and no application to whitening agents has been known. The present inventors have completed the present invention based on the above findings.

[0006] That is, the present invention is a tyrosinase inhibitor comprising one or more selected from the following plant extracts.

(1) Secang (scientific name: Caesal)
pinia sappan) (2) Kedawang, scientific name: Parkia roxbu
rghii) (3) Daun sogo (4) Kembang melat
i, Scientific name: Jasminus sambac (5) Tempuyung, Scientific name: Sonchus
arvensis L.) (6) Orang aring (scientific name: E)
clipta alba L.) (7) Kemukus (scientific name: Piper cubeba) (8) Kayu putih (scientific name: Eucal)
yptus alba) (9) Tumbar (scientific name: Coriandrum sativ)
um L.) (10) Bendo (11) Down trawas (scientific name: Litsea odorifera Val.) (12) Belantas (scientific name: Pluchea i)
ndica L.) (13) Cabe Java, Scientific name: Piper
retrofractum Vahl.) (14) Widoro upas (scientific name: Meremia mammosa Choir.) (15) Bottle (scientific name: Psomocarpus tetrago)
nolobus) (16) Kayu rape, scientific name: Parame
ria laevigata) (17) Keci beling (scientific name: Se
ricocalyx cruspus)

Hereinafter, the configuration of the present invention will be described in detail. Plants used in the present invention are plants that grow 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, flowers, bark, seeds or fruits, whole plant, etc. together with an extraction solvent, followed by filtration and concentration. The extraction solvent used in the present invention may be any solvent that is generally used for extraction, and in particular, alcohols such as methanol and ethanol,
Organic solvents such as hydrous alcohols, acetone and ethyl acetate can be used alone or in combination.

The blending amount of the plant extract in the present invention is 0.0005 to 20.0% by weight, preferably 0.001 to 10.0% by weight, as a dried product in the total amount of the external preparation.
If the amount is less than 0.0005% by weight, the effects of the present invention cannot be sufficiently exerted, and if it exceeds 20.0% by weight, it is difficult to formulate the composition, which is not preferable. Further, even if the content is 10.0% by weight or more, the effect is not so much improved.

[0010] In addition, the tyrosinase inhibitor of the present invention includes:
In addition to the above essential components, components commonly used in external preparations for skin such as cosmetics and pharmaceuticals, for example, other whitening agents, humectants, antioxidants, oily components, ultraviolet absorbers, surfactants, thickeners, alcohols Classes, powder components, coloring agents, aqueous components, water, various skin nutrients, and the like can be appropriately compounded as necessary.

In addition, 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 karin fruit, various crude drugs, drugs such as tocopherol acetate, glycyrrhizic acid and derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid and the like Other whitening agents, sugars such as glucose, fructose, mannose, sucrose, trehalose and the like can also be appropriately compounded.

The tyrosinase inhibitor of the present invention may be any of those conventionally used in external preparations for skin, such as ointments, creams, emulsions, lotions, packs, baths, etc., and the dosage form is not particularly limited.

[0013]

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 the examples, test methods and results of the tyrosinase activity inhibitory effect of the plant extract of the present invention will be described.

Test Method and Results 1. Sample Preparation (1) Secan Extract Solution 50 g of the tree portion of Secang was added at room temperature to 1
The extract was immersed in ethanol for a week and concentrated to obtain 3.3 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) Kedawang Extract Solution 50 g of Kedawang seed portion was immersed in ethanol for 1 week at room temperature, and the extract solution was concentrated to obtain 2.0 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.

(3) Down Sogo
Extract liquid 50 g of whole grass of Down Sogo (Daun sogo),
It was immersed in ethanol at room temperature for 1 week and the extract was concentrated to obtain 1.2 g of ethanol extract. DMSO
And the concentration was adjusted by diluting this solution, and the following experiment was performed using this.

(4) Kembang Melati
melati) extract Kembang melati
50g of the flower part is immersed in ethanol at room temperature for 1 week,
The extract was concentrated to obtain 4.8 g of 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.

(5) Tempuyun Extract Liquid 50 g of the grass portion of Tempuyun is
The extract was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 5.5 g of an ethanol extract. DMSO
And the concentration was adjusted by diluting this solution, and the following experiment was performed using this.

(6) Orang ari
ng) Extract 50 g of orang alling
g was immersed in ethanol for 1 week at room temperature, and the extract was concentrated to obtain 5.15 g of 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.

(7) Kemukus Extract Solution 50 g of the fruit portion of Chemuxus was immersed in ethanol at room temperature for 1 week, and the extract solution was concentrated to obtain 0.6 g of an ethanol extract. This extract was added to DMSO for 1
%, And the concentration was adjusted by diluting this solution. Using this, the following experiment was performed.

(8) Kayu puti
h) Extract 50 Kayu putih bark
g was immersed in ethanol for 1 week at room temperature and the extract was concentrated to obtain 1.2 g of an ethanol extract. This extract is D
After dissolving 1% in MSO and diluting this solution to adjust the concentration, the following experiment was performed using this.

(9) Tumbar Extract Liquid 50 g of the fruit portion of Tumbar was immersed in ethanol at room temperature for 1 week, and the extract liquid was concentrated to obtain 0.6 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.

(10) Bend (Bendo) Extraction Solution 50 g of the whole plant of Bend (Bendo) was immersed in ethanol at room temperature for 1 week, and the extraction solution was concentrated to obtain 4.6 g of an ethanol extract. Dissolve this extract in DMSO 1%,
This solution was diluted to adjust the concentration, and the following experiment was conducted using this solution.

(11) Down Traverse
was) extract whole plant of Down trawas (Daun trawas)
0 g was immersed in ethanol for 1 week at room temperature and the extract was concentrated to obtain 0.83 g of 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.

(12) Belantas extract 50 g of the whole plant of Belantas was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 2.5 g of an ethanol extract. This extract was added to DMSO for 1
%, And the concentration was adjusted by diluting this solution. Using this, the following experiment was performed.

(13) Cave Java
Extract solution 50g of the fruit of Cabe Java
Was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 0.3 g of an ethanol extract. This extract is D
After dissolving 1% in MSO and diluting this solution to adjust the concentration, the following experiment was performed using this.

(14) Widoro u Pass
50 g of the tuber portion of Widoro upas was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 1.7 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.

(15) Bottle Extract Solution 50 g of the seed portion of the bottle was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 1.8 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.

(16) Kayu rapet
Extract 50g bark of Kayu rapet
Was immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 1.2 g of ethanol extract. This extract is D
After dissolving 1% in MSO and diluting this solution to adjust the concentration, the following experiment was performed using this.

(17) Keci belin
g) Extract 50 leaves of Keci beling
g was immersed in ethanol for 1 week at room temperature and the extract was concentrated to obtain 1.5 g of an ethanol extract. This extract is D
After dissolving 1% in MSO and diluting this solution to adjust the concentration, 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. in a CO ₂ incubator (95% air, 5% carbon dioxide) at 37 ° C. 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, and the tyrosinase activity inhibitory effect is measured by the following method did.

3. 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, the same test as described above was conducted on an ethanol extract of a scallop (Lamiaceae: Subfamily Lamiaceae) 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.

[0033]

[Table 1] ───────────────────────────── Test tyrosinase activity (%) ─────────── ────────────── Concentration (wt%) 10 ^-5 10 ^-4 10 ^-3 10 ^-2 ─────────────────── ────────── Sekkan extract 68 77 27 Toxic Kedawan extract 69 64 69 72 Down Sogo extract 31 59-Toxic Kenban Melati extract 50 44 35 Toxic tempuyan extract-84 71 76 Oran・ Allin extract 76 76 68 Toxic Chemx extract − − 33 Toxic Kayu-Petit extract − − 59 Toxic Thumbal extract − − 79 Toxic bend extract 87 88 70 Toxic Down-Trawas extract − − 69 Toxic verantas extract − − 75 Toxic cabbage and Java extract − − 44 Toxic widow-upus extract 92 − − Toxic bottle extract 73 − 79 − Kayu la Extract − − − 47 Poppy Velin extract 69 76 − 85 Kaigai extract − − − 55 ───────────────────────────── ─

Hereinafter, examples of blending various dosage forms of the tyrosinase inhibitor according to the present invention will be described as examples.

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 Cecan methanol extract 0.01 Caustic potash 0 .2 Sodium bisulfite 0.01 Preservative Suitable amount Perfume Suitable amount Ion-exchanged water Residue (production method) Dissolve propylene glycol, sequan-methanol extract and caustic potash in ion-exchanged water and heat to 7
Keep at 0 ° C. (aqueous phase). Mix other ingredients and heat to melt
Keep at 0 ° 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 Secan ethanol extract 0.05 Sodium bisulfite 0.03 Ethylparaben 0.3 Perfume proper 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 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 kedawan acetone extract 0.05 kedawan ethanol extract 0.05 sodium bisulfite 0.03 ethylparaben 0.3 perfume proper amount ion-exchanged water residual (production method) ion-exchanged water Soap powder and borax are added to the mixture, heated and melted 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% by weight 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) Kedawan acetic acid ethyl ester extract 0.01 Sodium bisulfite 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 are added to the remaining ion-exchanged water, dissolved 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 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 mol ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Down Sogoacetone extract 10.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Fragrance 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 Down Sogo 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate-3 sodium-2 Water 0.05 Methylparaben 0.2 Perfume Suitable amount Ion-exchanged water Residual (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while down-sogo 50% ethanol aqueous solution extract in 95% ethanol, polyoxyethylene ( 50 moles) oleyl Was dissolved Le call ether, is added to the aqueous phase. Next, after adding other ingredients, caustic soda,
Thicken by neutralizing with L-arginine.

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 Kenban Melati Methanol extract 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 Residual (manufacturing method) Phases A and C are uniformly dissolved, and A is added to phase C
Add phase and solubilize. Next, after adding the phase B, filling is performed.

Example 8 Pack (formulation) (Phase A) 5.0% by weight dipropylene glycol Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Kenban Melatimethanol 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,
Phase B is added to the phase to solubilize it. 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 octanoate 2.0 tempuyan ethanol extract 1.0 preservative appropriate amount perfume appropriate amount (manufacturing method) Talc-black iron oxide powder component is sufficient with a blender After mixing, an oily component of squalane to isocetyl octoate, a tempuyan ethanol extract, an antiseptic and a fragrance are added and kneaded well, 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 (aqueous phase) purified water 50.0 1,3-butylene glycol 4.5 temp Yang 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 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.

Example 11 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 oran / allin acetone extract 0.05 oran / allin ethanol extract 0.05 sodium bisulfite 0.03 ethylparaben 0.3 perfume proper amount ion-exchanged water residual (manufacturing method) ion Soap powder and borax are added to exchanged water, and the mixture is heated and melted 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 12 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 3. 0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (Brand name: Carbopol 941, BFGoodrich Chemical company) Oran alline acetic acid ethyl ester extract 0.01 Sodium hydrogen sulfite 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 ingredients are mixed, heated and melted and maintained 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 13 Emulsion (Formulation) Microcrystalline wax 1.0 wt% Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 4.0 Polyoxyethylene (20 moles) ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Chemxacetone 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 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 14 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 Chemx 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 Residue (production method) Carbopol 940 was uniformly dissolved in ion-exchanged water, while Chemx 50% ethanol aqueous solution extract and polyoxyethylene (50 mol) oleyl in 95% ethanol. Arco 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 15 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 Kayu / Petitacetone extract 0.05 Kayu / Petitethanol extract 0.05 Sodium bisulfite 0.03 Ethylparaben 0.3 Perfume suitable amount Ion-exchanged water Residual (manufacturing) ion Soap powder and borax are added to exchanged water, and the mixture is heated and melted 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 16 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) Kayu-Peti 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 ingredients are mixed, heated and melted and maintained 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 17 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 Tumvalacetone extract 10.0 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Perfume proper 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 18 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 Tumval 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate ・ 3 sodium ・ 2 water 0 .05 Methylparaben 0.2 Fragrance Suitable amount Ion-exchanged water Residue (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while Tumval 50% ethanol aqueous solution extract and polyoxyethylene (50 mol) oleyl in 95% ethanol. Arco 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 19 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 bend 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 octoate, a bend ethanol extract, an antiseptic and a fragrance are added, and the mixture is well kneaded and then filled into a container and molded.

Example 20 Emulsion 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 Bend ethanol Extract 1.5 Sorbitan sesquioleate 3.0 Preservative Suitable amount Fragrance Suitable amount (Production method) After stirring the aqueous phase with heating, a 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.

Example 21 Cream (Formulation) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Down-Trawas methanol extract 01 caustic potash 0.2 sodium bisulfite 0.01 preservative proper amount perfume proper amount ion-exchanged water residual (manufacturing method) propylene glycol, down-Trawas methanol extract and caustic potash were added and dissolved in ion-exchanged water,
Heat and maintain at 70 ° C. (aqueous 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 a reaction. After that, homogenize with a homomixer,
Cool to 30 ° C with good stirring.

Example 22 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 Down-Trawas ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Fragrance suitable amount Ion-exchanged water Residual (production method) To ion-exchanged water Add propylene glycol,
Heat and maintain 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 to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring.

Example 23 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 Berantas acetone extract 0.05 Berantas ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Fragrance suitable amount Ion exchange water Residual (production method) Ion exchange water Soap powder and borax are added to the mixture, heated and melted 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 24 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) Berantas acetic acid ethyl ester extract 0.01 sodium bisulfite 0.01 ethylparaben 0.3 perfume proper 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 ingredients are mixed, heated and melted and maintained 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 25 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 Kabe Javaacetone extract 10.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Fragrance Ion-exchanged water Residual (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, 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 26 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 Kabe Java 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate-3 sodium-2 Water 0.05 Methylparaben 0.2 Perfume Appropriate amount Ion-exchanged water Residual (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, meanwhile, 95% ethanol is a 50% ethanol aqueous solution of kabe-Java, polyoxyethylene ( 50 mol) Orei Was dissolved alcohol ether, is added to the aqueous phase. Next, after adding other ingredients, caustic soda,
Thicken by neutralizing with L-arginine.

Example 27 Cream (formulation) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Widro-upus methanol extract 0. 01 Caustic potash 0.2 Sodium bisulfite 0.01 Preservative proper amount Perfume proper amount Ion-exchanged water Residue (production method) Dissolve propylene glycol, Widro-Upas methanol extract and caustic potash in ion-exchanged water
Heat and maintain at 70 ° C. (aqueous 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 a reaction. After that, homogenize with a homomixer,
Cool to 30 ° C with good stirring.

Example 28 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 Widro-upus ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume suitable amount Ion-exchanged water Residue (production method) To ion-exchanged water Add propylene glycol,
Heat and maintain 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 to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring.

Example 29 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 moles) ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Bottle acetone extract 10.0 Sodium hydrogen sulfite 0.01 Ethyl paraben 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 30 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 Bottle 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate ・ 3 sodium ・ 2 water 0 .05 Methylparaben 0.2 Fragrance Appropriate amount Ion-exchanged water Residue (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while a bottle 50% ethanol aqueous solution extract and polyoxyethylene (50 mol) oleyl is added to 95% ethanol. alcohol 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 31 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Weight Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Kayu Rapemethanol 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: Carbo Pole 940, BFGoodrich Chemical company) Purified water Residue (production method) Phases A and C are uniformly dissolved, and A is added to phase C
Add phase and solubilize. Next, after adding the phase B, filling is performed.

Example 32 Pack (formulation) (Phase A) Dipropylene glycol 5.0% by weight Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Kayu-rapemethanol extract 0.01 Olive oil 5 0.0 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 Residue (Manufacturing method) Phase A, phase B, and phase C are uniformly dissolved,
Phase B is added to the phase to solubilize it. Next, this is added to the C phase and then filled.

Example 33 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 poppy berlin ethanol extract 1.0 preservative appropriate amount perfume appropriate amount (manufacturing process) Talc to black iron oxide powder component is sufficient with a blender Mix, and then add squalane to isocetyl octoate oil component, poppy berline ethanol extract, preservative,
Add fragrance and knead well, then fill and mold in a container.

Example 34 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 poppy Berrin ethanol extract 1.5 Sorbitan sesquioleate 3.0 Preservative proper amount Perfume proper amount (Production method) After heating and stirring the aqueous phase, a 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.

[0069]

As described above, the tyrosinase inhibitor of the present invention has an excellent tyrosinase activity inhibitory effect, and can be used to lighten pigmentation, spots, freckles, liver spots, etc. after sunburn, It has excellent effects and is also excellent in safety.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical display location A61K 7/00 A61K 7/00 K U X 7/48 7/48 C12N 9/99 C12N 9/99 (72) Inventor Hirohiko Sakamoto 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Stock company Shiseido Daiichi Research Center

Claims (2)

[Claims] A tyrosinase inhibitor comprising one or more selected from the following plant extracts: (1) Secang, Scientific name: Caesalpinia sappa
n) (2) Kedawang, scientific name: Parkia roxbu
rghii) (3) Daun sogo (4) Kembang melat
i, Scientific name: Jasminus sambac (5) Tempuyung, Scientific name: Sonchus
arvensis L.) (6) Orang aring (scientific name: E)
clipta alba L.) (7) Kemukus (scientific name: Piper cubeba) (8) Kayu putih (scientific name: Eucal)
yptus alba) (9) Tumbar (scientific name: Coriandrum sativ)
um L.) (10) Bendo (11) Down trawas (scientific name: Litsea odorifera Val.) (12) Belantas (scientific name: Pluchea i)
ndica L.) (13) Cabe Java, Scientific name: Piper
retrofractum Vahl.) (14) Widoro upas (scientific name: Meremia mammosa Choir.) (15) Bottle (scientific name: Psomocarpus tetrago)
nolobus) (16) Kayu rape, scientific name: Parame
ria laevigata) (17) Keci beling (scientific name: Se
ricocalyx cruspus) 2. The amount of the plant extract is 0.0005 to 0.0005.
The tyrosinase inhibitor according to claim 1, which is 20.0% by weight.