JP3090291B2 - External preparation for fair skin - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for fair skin and, more particularly, to an external preparation containing lobeline and a derivative thereof as an active ingredient, which is stable on skin and excellent in fair skin effect.

[0002]

2. Description of the Related Art Kojic acid, ascorbic acid, hydroquinone, liquiritin and the like are known as substances having a fair-whitening effect, and plant-derived substances such as arbutin which is a hydroquinone glycoside in awaurushi and liquiritin in liquorice are known. It has been known. Loberin is a major alkaloid of the fennel plant Lobelia inflata L. In Japan, lobelia has been used as a respiratory stimulant and emetic for respiratory distress such as whooping cough and asthma. And lobeline hydrochloride, which is the hydrochloride of lobeline,
It is also used as an injection for respiratory palsy and oral medicine.

[0003] Further, in Chinese medicine, lobeline-containing plants such as Hanbe Lotus (original plant: Lobelia chinensisi)
L.), Yamabana (Original plant: Sawagikyo Lobelia sessilif)
olia L.) has been used externally and as an oral agent for snake bites, eczema, bruises, burns, diarrhea, toxicosis, acute tonsillitis, diuresis, etc. since ancient times. The pharmacological actions of lobeline include respiratory excitement, vomiting,
Further, bradycardia, blood pressure decrease, bronchial muscle contraction, etc. due to vagal central excitation are known. Loverin is known to have many similar effects to nicotine. For example, effects on the autonomic ganglion and motor skeletal muscle junctions, and effects on the circulatory system are similar to nicotine.

As described above, lobeline (or a salt thereof) and a plant containing them (eg, lobelia)
Was previously frequently used as a respiratory stimulant, especially for asphyxiation of newborns. However, although it is fast-acting, it has a short duration of action and is uncertain in its action, and may cause strong suppression after agitation. On the other hand, recently, a new use method focusing on the similarity of the pharmacological actions of lobeline and nicotine has been considered. For example,
Its effectiveness as a smoke-saving and smoking-suppressing agent, that is, the use of lobeline as a nicotine-like agent, and its application as a patch which is easy to use has also been proposed (JP-A-1-197435).

As another use of lobeline, it has been reported that a copper electrodeposited product having a stable hardness can be obtained by using it in combination with thiourea at the time of copper plating (Japanese Patent Publication No. 58-48037). Like this, lobelin,
The effective use of the pharmacological action of the derivative or the plant containing them is conventionally as respiratory agitation, bite, diuresis or smoke-saving and smoking suppressant, and other effective pharmacological actions are not known or used. It has not been. In particular, the use of topical preparations, especially fair-skin external preparations, has not yet been considered, and in the past, it has been confirmed as safe for injections and oral medicines, and for external use as a folk medicine for a long time. There has been a desire for new uses of the derivatives or plants containing them.

[0006]

On the other hand, there have been proposed and practically used many whitening agents. However, in terms of effect, safety, stability, and supplyability, it has not yet been found that any material for an external preparation satisfies all of them. For example, kojic acid is effective,
Although it is excellent in safety and supplyability, in terms of stability, it has the drawback of binding and coloring with metal ions,
In addition, safety of hydroquinone is feared, and ascorbic acid and arbutin have weak effects and are irritating and sensitizing. In particular, there is a concern that arbutin is hydrolyzed to hydroquinone inside and outside the body. In addition, colored (yellow) in licorice in terms of supply of liquiritin
Separation and purification from flavonoids is troublesome, and low solubility in water and organic solvents is a drawback in pharmaceutical formulation. In view of such external preparations, which are products to be used directly on the human body, there is a demand for the development of a whitening agent having excellent effects, safety, stability and supply.

[0007]

[Means for Solving the Problems] The present inventors have conducted extensive research and search for a novel pharmacological action of lobeline and its use based on various problems of conventional whitening agents. A strong clearing effect was found. In addition, the present inventors have also discovered that this fairing effect is not limited to lobeline, but also to salts such as lobeline hydrochloride as a hydrochloride, lobeline derivatives and plants containing these.

[0008] The lobeline mentioned here is 2- [6- (2
-Hydroxy-2-phenylethyl) -1-methyl-piperidi
nyl] -1-phenylethanone; 2- [6- (β-hydroxy
-Phenethyl) -1-methyl-2-piperidyl] acetopheno
ne and derivatives are related compounds of lobeline or pip
It is a 1,2,6-position substitution of eridine. piperidine
In the 1, 2, and 6 positions, as shown below, H, CH_Three , C
H_Two CHOH-C₆ H _Five , CH_Two CO-C₆ H_Five Such as
The substituent is substituted.

## STR1 ## piperidine

Embedded image (Example) Loverine; R ₁ = CH ₃ , R ₂ = CH ₂ CHOH-C ₆ H ₅ ,
R ₃ = CH ₂ CO-C ₆ H ₅ Lobelanidine; R ₁ = CH ₃ , R ₂ = R ₃ = CH ₂ CHOH-C ₆ H ₅ Lobelanine; R ₁ = CH ₃ , R ₂ = R ₃ = CH ₂ CO -C ₆ H _{5 and} other lobeline derivatives or related compounds include, for example, Lobelidine, Norlobelanine, Norlobelani
dine, Lobinine, Lobinaline and the like.

In actual use, the above compounds may be used alone or in combination of two or more as external preparations. However, lobeline-containing plants such as Lobelia inflata
L. (Whole grass collected during the fruiting season: Lobeliae Herba, Indian
tobacco, Wild tobacco), Lobelia nicotianaefolia H
eyne, L. excelsa Lesch, Lobelia cardinalis L., L.ses
The same fair skin effect can be obtained as an extract of a plant such as silifolia Lamb., L. radicans Thunb.

[0010] In addition, one or more lobeline, lobeline derivative or plant extract containing the same may be used in combination with a conventionally known whitening agent such as kojic acid, ascorbic acid, hydroquinone, liquiritin and derivatives thereof, or a derivative thereof. When used in combination with a plant or the like, for example, an extract of ouarushi (arbutin), licorice (liquiritin), etc., the effect of the conventional whitening agent can be synergistically enhanced.

As kojic acid, the following formula (3)

Formula (3) A pure product of 5-oxy-2-hydroxymethyl-γ-pyrone represented by A product obtained by extracting kojic acid from the fermentation liquid and crystallizing the same is used.

Examples of such a strain having a kojic acid-producing ability include Aspergillus albus, Aspergillus candidas, Aspergillus oryzae, Aspergillus nidulans, Aspergillus paracitycus, Aspergillus awamori, Aspergillus tamari and Aspergillus newbuus. , Aspergillus flavus, Aspergillus wenchi, Aspergillus glaucus, Aspergillus cliibatas,
Strains of the genus Aspergillus, such as Aspergillus fumigatus, Aspergillus digantus, strains of the genus Penicillium such as Penicillium dalay, strains of the genus Escalaria such as Escalikia coli, Acetobacter acetylene, Acetobacter gluconica, Acetobacter xylinum, etc. And strains of the genus Gluconobacter such as Gluconobacter rosius and Gluconobacter gurnicas are preferably used.

The medium composition of these strains is as follows:
Usually, sucrose, sucrose, fructose, glucose, starch, maltose, glycerin, mannitol, rhamnose,
Carbon sources such as xylose, gluconic acid, arabinose, dihydroxyacetone, inosit, lactose, and ethanol are about 2 to 15% (% by weight, the same applies hereinafter), ammonia sulfate, polypeptone, sodium nitrate, baker's yeast extract, brewer's yeast extract, etc. About 0.1 to 1 nitrogen source
%, About 0.01% of magnesium source such as magnesium sulfate
To 0.05%, phosphorus and potassium sources such as potassium monohydrogen phosphate and potassium dihydrogen phosphate are 0.01 to 0.1%, and other inorganic substances such as ferric sulfate, ferric chloride, sodium chloride and calcium chloride. Salts of about 0.001 to 0.005% may be employed.

The kojic acid derivatives used in the present invention include 2-methoxymethyl-hydroxy-4H-pyran-4-one, 2-ethoxymethyl-5-hydroxy-4H-pyran-4-one, 2-benzo Ruyloxymethyl-5-hydroxy-4H-pyran-4-one, 2-
Cinnamoyloxymethyl-5-hydroxy-4H-pyran-4-one, 2-phenoxymethyl-5-hydroxy-4H-pyran-4-one, kojic acid glycoside or
The following equation (4)

Formula (4) (Wherein, R is a saturated or unsaturated aliphatic hydrocarbon group).
In the formula, as the saturated or unsaturated aliphatic hydrocarbon group represented by R, a saturated or unsaturated aliphatic carboxylic acid is exemplified.

The saturated aliphatic carboxylic acids include, for example, acetic acid, propionic acid, n-valeric acid, isovaleric acid, methylethylacetic acid, trimethylacetic acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylic acid , Lauric acid, tridecylic acid, myristic acid, pentadecylic acid, palmitic acid, margaric acid, stearic acid, non-deleric acid, arachinic acid or lignoceric acid, etc. are used, but in order to reduce the skin irritation of the acid, the carbon number It is preferable to use a saturated aliphatic carboxylic acid having 8 or more, particularly a saturated aliphatic carboxylic acid having 14 to 20 carbon atoms. The use of the aliphatic carboxylic acid having more than 20 carbon atoms is not particularly limited, but it is extremely difficult to obtain the aliphatic carboxylic acid, which is not preferable from the viewpoint of production cost. In addition to these saturated aliphatic carboxylic acids, for example, unsaturated aliphatic carboxylic acids such as linoleic acid, linolenic acid, maleic acid, fumaric acid, olefin acid, and arachidonic acid may be used without any particular limitation. Can be

The kojic acid glycoside is obtained by stabilizing a kojic acid molecule by linking a saccharide to the -CH ₂ OH group at the 2-position of kojic acid. Has the structural formula shown.

Formula (5) In the formula (5), R is a hexose, a pentose, an amino acid, a disaccharide, or a trisaccharide. Examples of the hexose include glucose, galactose, mannose, fructose, and sorbose. Examples of the saccharide include ribose, arabinose, xylose, liquorice, and xylulose.Examples of the amino saccharide include glucosamine, mannosamine, and galactosamine.Examples of the disaccharide include maltose, lactose, cellobiose, and sucrose. Examples of the trisaccharide include maltotriose, cellotriose and the like.

The kojic acid glycoside of the present invention can be produced by any of a synthetic method, an enzymatic method and a culture method, and any of them can be used. However, in view of productivity and economic efficiency, A kojic acid glycoside produced by an enzymatic method or a culture method is preferred. Generally, it is synthesized by utilizing a glycosyltransfer reaction of an enzyme, for example, amylase, phosphorylase, lysozyme or the like, or is produced by chemically binding kojic acid to an unreacted -OH group at position 1 of a sugar. Can be.

Examples of the ascorbic acid derivative include known derivatives such as glycosides such as glucoside ascorbic acid, L-ascorbyl palmitate, L-ascorbyl isopalmitate, L-ascorbyl dipalmitate and L-isopalmitate. -Ascorbyl, L-ascorbyl stearate, L-ascorbyl isostearate, L-ascorbyl distearate, L-ascorbyl diisostearate, L-ascorbyl myristate, L-ascorbyl isomyristate, L-ascorbyl dimyristate, diisomyristin Acid L-ascorbyl, 2-ethylhexanoic acid L-ascorbyl, di-2-
L-ascorbyl ethylhexanoate, L-ascorbyl oleate, L-ascorbyl dioleate, etc.
L-ascorbic acid phosphates such as L-ascorbic acid-2-phosphate, L-ascorbic acid-3-phosphate;
L-ascorbic acid sulfates such as L-ascorbic acid-2-sulfate and L-ascorbic acid-3-sulfate; alkali metal salts such as sodium and potassium; alkaline earth metals such as calcium and magnesium Salt and the like.

Examples of the hydroquinone derivative include arbutin and the like.

Examples of the liquiritin derivative include liquiritin-α- having liquiritin and α-linked glucose.
Glucosides, liquiritin-α-maltosides and the like can be mentioned.

Examples of a solvent for extracting a plant containing lobeline or a lobeline derivative include a mixture of water and a polar solvent such as alcohol and acetone at an arbitrary ratio, alcohol, acetone, chloroform, ethyl acetate, diethyl ether, benzene and the like. Selected from organic solvents alone or in any combination.

Extracts such as plants containing a conventional whitening agent, such as ouarushi and licorice, include water, alcohol, acetone, chloroform, ethyl acetate,
It is obtained by an extraction solvent such as diethyl ether or benzene alone or in combination.

<Blending Concentration> The complexion external preparation of the present invention is prepared by blending the above-mentioned active ingredient in a known dosage form such as pharmaceuticals, quasi-drugs, and cosmetics. Like. (1) Roverine or a lobeline derivative is incorporated alone or in combination in a total amount of 0.01 to 10.0%, preferably 0.1 to 5%. (2) The extract of plants containing lobeline or a lobeline derivative may be used alone or in combination in an amount of 0.1 to 2%.
0.0%, preferably 0.5 to 10.0%. (3) A conventionally known lightening agent such as kojic acid, ascorbic acid, hydroquinone, liquiritin or a derivative thereof is incorporated, alone or in combination, in an amount of 0.01 to 10%, and lobeline or a lobeline derivative is used alone or in combination. In total, 0.1 to 10 times the amount of extract such as lobeline or a lobeline derivative-containing plant is used alone or in combination for 1 to 5 times.
Mix 0 times the amount. (4) A conventionally known whitening agent, for example, an extract of a plant containing kojic acid, ascorbic acid, hydroquinone, liquiritin and a derivative thereof, or the like is used alone or in combination in an amount of 0.1 to 20%. The lobeline or lobeline derivative is used alone or in combination in a total amount of 0.01 to 1 times, and the extract of lobeline or a lobeline derivative-containing plant or the like is used alone or in combination in a total amount of 0.1 to 10 times.

When preparing the external preparation of the present invention, various known active ingredients usually used, for example, carpronium chloride, cepharanthin, vitamin E, vitamin E nicotinate, nicotinic acid, nicotinamide, benzyl nicotinate, and shochu Peripheral vasodilators such as tincture and tincture tincture, cooling agents such as camphor and menthol, antibacterial agents such as hinokitiol, benzalkonium chloride, undecylenic acid, anti-inflammatory agents such as lysozyme chloride, glycyrrhizin, allantoin, assembly extract, garlic extract, Carrot extract, gongo extract, rosemary extract, aloe extract, luffa extract, ginkgo extract,
Various extracts derived from animals, plants and microorganisms, such as elder extract, placenta extract, liver extract, and lactic acid bacteria culture extract, can be freely added and used.

The known forms of pharmaceuticals, quasi-drugs, and cosmetics mean all forms that can be used externally, such as cataplasms, plasters, pastes, creams, ointments, aerosols, emulsions, lotions, emulsions, Essence, pack, gel, powder, foundation, sun care,
An external preparation for skin such as bath salt can be exemplified. In addition, in addition to known active ingredients, surfactants, and base components such as oils and fats in the above-mentioned medicines, quasi-drugs, and cosmetics, known humectants, thickeners, preservatives, and oxidizers as necessary. It goes without saying that various additives such as an inhibitor, an ultraviolet absorber / scattering agent, a chelating agent, a pH adjuster, a fragrance and a coloring agent can be used in combination.

Examples of the humectant include polyhydric alcohols such as glycerin, propylene glycol, 1,3 butylene glycol, sorbitol, mannitol, polyethylene glycol, dipropylene glycol, amino acids,
NMF components such as sodium lactate and sodium pyrrolidonecarboxylate, hyaluronic acid, collagen, elastin,
Examples include chondroitin sulfate, dermatan sulfate, fibronectin, ceramides, heparin-like substances, and water-soluble polymer substances such as chitosan.

Examples of the thickener include natural alginates such as sodium alginate, xanthan gum, aluminum silicate, quince seed extract, tragacanth gum, starch and the like, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, soluble starch and cationized cellulose. Examples include semi-synthetic polymer substances, synthetic polymer substances such as carboxyvinyl polymer and polyvinyl alcohol.

As preservatives, for example, benzoate, salicylate, sorbate, dehydroacetate, paraoxybenzoate, 2,4,4'-trichloro-2'-
Examples thereof include hydroxydiphenyl ether, 3,4,4′-trichlorocarbanide, benzalkonium chloride, hinokitiol, resorcinol, ethanol and the like.

Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, and gallic propyl.

Examples of the ultraviolet absorber include 4-methoxybenzophenone, octyldimethylparaaminobenzoate, ethylhexylparamethoxycinnamate, titanium oxide, kaolin, and talc.

Further, examples of the chelating agent include ethylenediaminetetraacetate, pyrophosphate, hexametaphosphate, citrate, tartaric acid, gluconic acid and the like. ,
Examples thereof include potassium hydrogen phosphate.

[0032]

EXAMPLES Next, examples of the present invention and test examples of the effects thereof will be described, but these do not limit the present invention in any way.

<Production Example> (Production of methanol extract and extract of Lobelia Herba) Above flowering part (Lo) of Lobelia inflata L.
After drying belia Herba), 1 kg of the minced product is immersed in 5 L of methanol. After immersion at room temperature all day and night, stirring several times, filtration is performed to obtain a methanol extract. The residue was extracted and filtered in the same manner three times each with 5 L of methanol, and the filtrate was evaporated, and the solvent was distilled off (concentrated) under reduced pressure to obtain 124 g of a methanol extract (216 g of a methanol extract).

(Production of lobeline) 100 g of Lobelia Herba methanol extract was extracted with a 2% tartaric acid solution, and the insoluble matter was filtered. Then, the tartaric acid extract and chloroform were distributed to obtain an aqueous layer. The aqueous solution was converted to an alkali with 14% ammonia under ice-cooling, then extracted with chloroform, and the solvent was distilled off to obtain a crude alkaloid. The obtained crude alkaloid was purified using silica gel (methanol-chloroform solvent) and Sephadex.
LH-20 (manufactured by PHARMACIA, water-methanol solvent) and
Repeated column chromatography using MCL-gel CHP20P (manufactured by MITSUBISHI KASEI, water-methanol solvent) 23
1 mg of lobeline was obtained.

(Manufacture of Lobelanine) 100 g of Lobelia Herba methanol extract was extracted with a 2% tartaric acid solution, the insolubles were filtered, and the tartaric acid extract and chloroform were partitioned to obtain an aqueous layer. The aqueous solution was converted to an alkali with 14% ammonia under ice-cooling, then extracted with chloroform, and the solvent was distilled off to obtain a crude alkaloid. The obtained crude alkaloid was purified using silica gel (methanol-chloroform solvent) and Sephadex.
Purified by column chromatography using LH-20 (Pharmacia, water-methanol solvent), 21 mg of Lobe
Got lanine.

(Production of Licorice Ethanol Extract) Licorice
After drying the root and stron of Glycyrrhiza glabra L.,
1 kg of the shredded pieces are immersed in 5 L of ethanol. After soaking at room temperature for 24 hours, stirring several times, the mixture is filtered to obtain an ethanol extract. The residue was extracted and filtered three times in total with 5 L of ethanol, and the filtrate was evaporated. The solvent was distilled off under reduced pressure to obtain 103 g of an ethanol extract.

(Production of liquiritin) 20 g of licorice ethanol extract was dissolved and suspended in 1 L of n-butanol, and 1 L of water was added thereto for distribution. The solvent is distilled off from the n-butanol layer under reduced pressure to obtain a crude liquiritin extract. The obtained crude liquiritin extract was separated using Sephadex LH-20 (Pharmacia,
Purification by column chromatography using a water-methanol-acetone solvent) gave 719 mg of liquiritin.

(Manufacture of methanol extract of Uwaurushi) Extract of bearberry, Arctostaphylos uva-ursi (LINNE) SPREN
After drying the leaves of G., 1 kg of chopped 5 L of methanol
Soak with. After immersion at room temperature all day and night, stirring several times, filtration is performed to obtain a methanol extract. Residues are each 5 L of methanol
In the same manner, extraction and filtration were carried out three times, and the filtrate was evaporated, and the solvent was distilled off under reduced pressure to obtain 196 g of a methanol extract.

(Manufacture of arbutin) A solution of 10 g of Uwaurushi methanol extract dissolved and suspended in 30 g of methanol was mixed with Sephadex LH-20 (manufactured by Pharmacia, water-methano-
Purification was repeated by column chromatography using a chlorobutyric solvent to obtain 0.89 g of arbutin.

(Production of methanol extract of half lotus lotus) After drying the whole plant of Lobelia chinensis L., 1 kg of the cut pieces is immersed in 5 L of methanol. After immersion at room temperature all day and night, stirring several times, filtration is performed to obtain a methanol extract. The residue was extracted and filtered three times in total with 5 L of methanol each time, and the filtrate was distilled off, and the solvent was distilled off under reduced pressure.
g of methanol extract was obtained.

<Experimental example> (Method of whitening test using mouse melanoma B16 cells)
Adjust the sample in MEM (Eagle's Minimum Essential Medium) so that the final concentration is as shown in Tables 1 to 8,
It was dissolved and filtered through a sterilizing filter having a pore size of 0.45 μm. The sample insoluble in MEM was dissolved in 100 μl of ethanol and then added to MEM. 8 ml of MEM, 1 ml of FBS (fetal bovine serum) and 8 ml of FBS (fetal bovine serum) obtained by dissolving and filtering the sample in two plastic dishes (Falcon, 9 cm inside diameter)
1 × 10 ⁵ cells / ml of B16 cells suspended in 1 ml of MEM were added, and cultured at 37 ° C. under 5% CO ₂ and 95% air.
Three days after the start of the culture, the medium was replaced and the cells were cultured for a total of 5 days.
After culturing, collect the cells grown at the bottom of the chalet.
Suspend in hate buffered saline (PBS) for 2,000 r
After centrifugation at pm for 3 minutes, the degree of blackening of the obtained cell pellet was visually evaluated. In Tables 1 to 8,
+-In the visual color tone indicates the following evaluation. -: Shows the same degree of blackening as the non-added group. +: Shows a slightly lower degree of blackening than the non-added group. ++: The degree of blackening is clearly lower than in the non-added group. +++: Degree of blackening slightly observed. ++++: White to gray, not recognized as black. ++++++: White

[0042]

[0043]

[0044]

[0045]

[0046]

[0047]

[0048]

[0049]

<Prescription Example> Next, a prescription example is shown. In the prescription example,
"Appropriate amount" means the ratio of the entire formulation to 100% by weight.

(1) <Solution> Weight (%) Loverin 0.50 Glycerin 5.00 Sorbitol 4.00 Polyoxyl stearate 40 1.55 Ethanol 10.00 Purified water Appropriate amount Each component is mixed and stirred. Dissolve to make a solution.

(2) <Solution> weight (%) lobeline hydrochloride 1.00 glycerin 5.00 sorbitol 4.00 polyoxyl stearate 40 1.55 ethanol 10.00 purified water appropriate amount These are dissolved to prepare a liquid preparation.

(3) <Solution> weight (%) lobeline hydrochloride 1.00 Lobelanine 0.10 glycerin 5.00 sorbitol 4.00 polyoxyl stearate 40 1.55 ethanol 10.00 purified water qs. After mixing and stirring, these are dissolved to prepare a liquid preparation.

(4) <Solution> Weight (%) Hydroquinone 0.01 Lobelanine 0.10 Glycerin 5.00 Sorbitol 4.00 Polyoxyl stearate 40 1.55 Ethanol 10.00 Purified water Appropriate amount Mix and stir each component Then, these are dissolved to prepare a liquid preparation.

(5) <Solution> weight (%) kojic acid glucoside 0.10 lobeline hydrochloride 0.50 glycerin 5.00 sorbitol 4.00 polyoxyl stearate 40 1.55 ethanol 10.00 purified water qs The components are mixed and stirred, and these are dissolved to produce a liquid preparation.

(6) <Emulsion> Weight (%) 1,3-butylene glycol 4.00 purified water qs. Ethanol 10.00 Lobelia Herba Methanol extract 1.00 Polyethylene glycol 400 6.00 Purified water 20.00 A and B are heated, and A is added to B to prepare an emulsion.

(7) <Emulsion> Weight (%) 1,3-butylene glycol 4.00 Kojic acid 0.50 Purified water q.s. Ethanol 10.00 Lobelia Herba Methanol extract 1.00 Polyethylene glycol 400 6.00 Purified water 20.00 A and B are heated, and A is added to B to prepare an emulsion.

(8) <Emulsion> Weight (%) 1,3-butylene glycol 4.00 kojic acid 0.20 ascorbic acid 0.05 purified water q.s. Ethanol 10.00 Lobelia Herba Methanol extract 1.00 Half side lotus methanol extract 0.75 Polyethylene glycol 400 6.00 Purified water 20.00 Heat A and B, add A to B to make emulsion .

(9) <Emulsion> Weight (%) 1,3-butylene glycol 4.00 arbutin 0.10 kojic acid glucoside 0.10 ascorbic acid glucoside 0.05 purified water qs. Ethanol 10.00 liquiritingenin 0.05 Lobelia Herba methanol extract 1.55 half lotus methanol extract 0.75 polyethylene glycol 400 6.00 purified water 20.00 Heat A, B, add A to B Make an emulsion.

(10) <Ointment> Weight (%) Polysorbate 20 5.00 Loverine 0.10 Ethanol 5.00 B. White petrolatum qs Tallow 20.00 cetanol 2.00 Glycerin monostearate 5.00 Liquiritin 0.10 A is stirred and mixed. B is mixed under heating and dissolved, and A is mixed with B at the time of cooling to prepare an ointment.

(11) <Ointment> Weight (%) Polysorbate 20 5.00 Lobelia Herba methanol extract 0.30 half lotus methanol extract 0.10 ethanol 5.00 White petrolatum qs Tallow 20.00 cetanol 2.00 Glycerin monostearate 5.00 Liquiritin 0.10 A is stirred and mixed. B is mixed under heating and dissolved, and A is mixed with B at the time of cooling to prepare an ointment.

(12) <Emulsion> Weight (%) White petrolatum 2.50 Silicon oil 0.50 Stearyl alcohol 2.20 Sucrose fatty acid ester 5.00 Octyldodecanol 2.20 Squalane 6.30 Jojoba oil 0.20 Polyoxyl stearate 40 2.50 B. Purified water qs Roverine hydrochloride 0.10 Kojic acid 0.50 Dipropylene glycol 3.00 Propylene glycol alginate 0.30 Xanthan gum 0.05 Heat A and B to dissolve. A is added to B to form an emulsion.

(13) <Emulsion> Weight (%) A. White petrolatum 2.50 Silicon oil 0.50 Stearyl alcohol 2.20 Sucrose fatty acid ester 5.00 Octyldodecanol 2.20 Squalane 6.30 Jojoba oil 0.20 Polyoxyl stearate 40 2.50 B. Purified water qs Roverine hydrochloride 0.40 Kojic acid 0.05 Arbutin 0.05 Ascorbic acid 0.05 Dipropylene glycol 3.00 Propylene glycol alginate 0.30 Xanthan gum 0.05 A and B are heated and dissolved. A is added to B to form an emulsion.

(14) <Cream> Weight (%) Purified water qs lobeline hydrochloride 0.50 kojic acid 0.05 1,3-butylene glycol 3.00 sorbitol 7.00 dl-PCA sodium (50%) 3.00 Polysorbate 60 2.50 Glyceride monostearate 1.50 Cetanol 3.00 Vaseline 5.00 Octyldodecyl myristate 5.00 Octyldodecanol 6.00 Squalane 15.00 Licorice ethanol extract 0.05 1,3-butylene glycol 1.00 Heat A and B to dissolve. Add B to A and emulsify to make a cream.

(15) <Cream> Weight (%) Purified water qs Arbutin 0.10 1,3-butylene glycol 2.50 Ascorbic acid glucoside 0.05 Sorbitol 7.00 dl-PCA sodium (50%) 3.00 Polysorbate 60 2.50 Glyceride monostearate 1.50 Cetanol 3.00 Vaseline 5.00 Octyldodecyl myristate 5.00 Octyldodecanol 6.00 Squalane 15.00 Half-edge lotus methanol extract 0.20 Uwaurushimethanol extract 0.01 1,3-butylene glycol 2.50 A and B are heated and dissolved. Add B to A and emulsify to make a cream.

(16) <Packing Agent> Weight (%) Carboxyvinyl polymer 1.40 dipropylene glycol 10.00 glycerin 3.00 diisopropanolamine 0.15 B. Triacetin 30.00 Xanthan gum 2.00 C.I. Purified water qs Roverine hydrochloride 0.50 A is mixed and dissolved to form a gel. Then, B and C are sequentially added to A to prepare a pack.

(17) <Packing Agent> Weight (%) Carboxyvinyl polymer 1.40 dipropylene glycol 10.00 glycerin 3.00 diisopropanolamine 0.15 B. Triacetin 30.00 Xanthan gum 2.00 C.I. Purified water qs Roverine hydrochloride 0.40 Kojic acid 0.40 A is mixed and dissolved to form a gel. Then, B and C are sequentially added to A to prepare a pack.

[0068]

The whitening external preparation containing lobeline or a derivative thereof as an active ingredient provided by the present invention is excellent in whitening action, has a stable supply property, and is excellent in skin safety and stability. And has a feature of exhibiting a synergistic fairness effect when used in combination with another fairing agent.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61K 7/00 A61K 7/00 X 31/445 31/445 A61P 17/00 A61P 17/00

Claims (3)

(57) [Claims] 1. An external preparation for fair skin, comprising lobeline or a derivative thereof as an active ingredient. 2. The external preparation according to claim 1, further comprising at least one whitening agent. 3. The method of claim 1, wherein the whitening agent is kojic acid, ascorbic acid,
3. The external preparation for fairness according to claim 2, which is at least one member selected from the group consisting of hydroquinone, liquiritin, and derivatives thereof.