JP2003313116A - Skin care preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation which contains a substance having excellent platelet activating factor (PAF) antagonism and a skin roughness- improving and preventing effect and a substance having a tyrosinase activity- inhibiting action as active ingredients. <P>SOLUTION: This skin care preparation is characterized by containing at least one of the following compounds 1 to 3 as an active ingredient. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for skin, particularly to its active ingredient.

[0002]

2. Description of the Related Art Conventionally, an active ingredient of an external preparation for skin which has an improving / preventing effect on skin roughness caused by skin diseases such as atopic dermatitis, contact dermatitis, eczema, psoriasis and on the skin roughness and roughness of healthy persons. As such, steroid drugs having an anti-inflammatory effect and vaseline, urea, heparin, various amino acids and lipids having a moisturizing effect have been used.

[0003]

However, steroids have strong side effects, and moisturizers do not always have sufficient effects, and there has been a demand for the development of superior active ingredients with higher safety. In recent years, platelet activating factor (platel) has been used to develop various inflammatory and allergic skin diseases and rough skin.
et activating factor, hereinafter referred to as PAF. ) Is becoming more involved. For example, in psoriasis, which is an inflammatory hyperkeratosis disease, the presence of high PAF is recognized in the affected epidermis. It has also been suggested that PAF is involved in allergic skin diseases such as atopic dermatitis, contact dermatitis and eczema. PAF is also
It is considered to play an important role also in the normal keratinization process of the epidermis such as keratin formation, and attempts have been made to use a PAF antagonist as a drug for improving rough skin or a drug for treating skin diseases. There is.

On the other hand, external preparations for skin are required to have functions other than improvement of rough skin, and a whitening agent is added for the purpose of whitening pigmentation such as spots, freckles, and liver spots due to abnormal deposition of melanin pigment. Has been done. Known whitening agents include vitamin C and its derivatives, kojic acid, arbutin, and the like, which suppress melanin production by suppressing the activity of tyrosinase, which is essential for melanin production. However, even with these, sufficient effects have not been obtained yet. The present invention has been made in view of the above-mentioned problems of the prior art, and one of the objects thereof is to have an excellent PAF antagonistic action and improve inflammatory / allergic skin diseases, rough skin of healthy people, and the like. It is intended to provide a substance, a PAF antagonist containing the same as an active ingredient, and a skin external preparation. Another object is to provide a substance having an excellent activity to suppress tyrosinase activity, which suppresses melanin production to exert a whitening effect, and a skin external preparation containing the same.

[0005]

Means for Solving the Problems As a result of intensive investigations by the present inventors in order to achieve the above-mentioned object, a certain methoxybenzene derivative and a specific component Cas of curcuminoids, Cas
Sumunarin B has an excellent PAF antagonism,
It has been found that these compounds improve rough skin with erythema, desquamation, dryness, eczema, itching and the like. Further, as a result of further investigation, they also found that they also have a tyrosinase activity inhibitory action and inhibit melanin production, and completed the present invention. That is, the external preparation for skin of the present invention is the following compound 1
It is characterized by containing at least 1 sort (s) of ~ 3 as an active ingredient.

[0006]

[Chemical 4]

[Chemical 5]

[0007]

[Chemical 6]

In the external preparation of the present invention, the compounds 1 to
It is preferable to incorporate an extract of a ginger genus plant of the ginger family containing at least one of 3 as an active ingredient.
In addition, in the external preparation of the present invention, it is preferable that at least one kind of the above compounds 1 to 3 or a ginger ginger genus plant extract containing the same is a rough skin improving agent. The platelet activating factor antagonist of the present invention is the compound 1
It is characterized by containing at least 1 sort (s) of ~ 3 as an active ingredient. In the antagonist of the present invention, the compounds 1 to
It is preferable to incorporate an extract of a ginger genus plant of the ginger family containing at least one of 3 as an active ingredient.
The tyrosinase activity inhibitor of the present invention is characterized by containing at least one of the compounds 1 and 2 as an active ingredient. In the inhibitor of the present invention, the compound 1
It is preferable to blend an extract of a ginger plant belonging to the ginger family Ginger, which contains at least one of No. 2 to 2 as an active ingredient. The whitening agent according to the present invention is characterized by containing the tyrosinase activity inhibitor as an active ingredient.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION Compounds 1 to 3 according to the present invention can be isolated from plants using known methods. For example, compounds 1 and 2 are Phytochemistry, vol.32, No.2,
p357-363, 1993 (Author: Akiko Jitoe, Toshiya Masuda,
and Nobuji Nakatani), compound 3 is JOCS, vol.72, No.9, p.1053, 1995 (Author: Tosh
iya Masuda, et.al.) can be used. As a plant, ginger family (Zingiberaceae)
Examples include Zingiber plants. Examples of the ginger plant of the ginger family include pontsu ginger and the like. Pontsuku ginger is native to tropical regions such as Okinawa and Southeast Asia, and the scientific name is Zingiber purpureum Roxb. Or Zingiber cassumunar. Zingiber purpureum Ro
It has been found that xb. and Zingiber cassumunar have a synonym relationship.

The site to be used is not particularly limited as long as Compounds 1 to 3 can be obtained. For example, roots, rhizomes, stems, leaves,
Flowers, fruits, whole plants and the like can be mentioned, but roots or rhizomes are preferable. As a specific example, the ground product of pontsu ginger root or rhizome is immersed in an extraction solvent at room temperature to under heating for extraction, and this extract is purified by column separation purification, recrystallization or the like to obtain compounds 1 to 3. Can be obtained.

The extraction solvent is not particularly limited, and examples thereof include water, primary alcohols such as methanol and ethanol,
Examples thereof include polyhydric alcohols such as 1,3-butylene glycol and propylene glycol, lower alkyl esters such as ethyl acetate, hydrocarbons such as benzene and hexane, ethyl ether, acetone and the like, and these may be used in combination of two or more kinds. it can. As a preferred extraction solvent,
Water, methanol, ethanol, 1,3-butylene glycol, or a mixed solvent thereof may be used.

In the present invention, in addition to compounds 1 to 3, extracts containing these as active ingredients can be used. Examples of such an extract include a primary extract extracted with the above extraction solvent, and a crude fraction obtained by roughly purifying the primary extract by silica gel chromatography or the like. As the compounds 1 to 3 of the present invention, it is possible to use not only those extracted from natural products but also synthetic products produced by chemical synthesis or the like. An example of a method for producing compounds 1 to 3 and a crude fraction containing these as active ingredients is shown below.

Production Example 1 Isolation of Compound 1 500 g of a rhizome of Zingiber purpureum Roxb. Was crushed and immersed in 2.5 L of methanol at room temperature for 1 week for extraction.
The extract was filtered and concentrated, and then the concentrate was subjected to silica gel column chromatography (eluent: n-hexane / ethyl acetate mixed system) to obtain a crude fraction. Furthermore, reversed-phase HPLC preparative (mobile phase: 60% acetonitrile, column: CAPSELLPAK C18 UG120Å manufactured by Shiseido Co., Ltd., column size: 10
Compound 1 was isolated by (mmφ × 250 mm, detection: UV 210 nm). Yield 410 mg, 0.082%. Table 1 shows the ¹³ C-NMR chemical shift values of Compound 1 together with literature values. Further, in Chemical formula 7, the carbon position No. of Table 1 is shown. The chemical structural formula corresponding to is shown.

[0014]

[Chemical 7]

[0015]

[Table 1]

Production Example 2 Isolation of Compound 2 500 g of a rhizome of Zingiber purpureum Roxb. Was crushed and immersed in 2.5 L of methanol for 1 week at room temperature for extraction.
The extract was filtered and concentrated, and then the concentrate was subjected to silica gel column chromatography (eluent: n-hexane / ethyl acetate mixed system) to obtain a crude fraction. Furthermore, reversed-phase HPLC preparative (mobile phase: 60% acetonitrile, column: CAPSELLPAK C18 UG120Å manufactured by Shiseido Co., Ltd., column size: 10
Compound 2 was isolated by (mmφ × 250 mm, detection: UV 210 nm). Yield 430 mg, 0.086%. Table 2 shows the ¹³ C-NMR chemical shift values of Compound 2 together with literature values. The carbon position numbers in Table 2 are in accordance with Chemical formula 7 above.

[0017]

[Table 2]

Production Example 3 Isolation of Compound 3 509.7 g of a rhizome of Zingiber purpureum Roxb. Was crushed and immersed in 2.5 L of methanol at room temperature for 1 week for extraction. After the extract is filtered and concentrated, the concentrate is a silica gel column (eluent: n-hexane / ethyl acetate mixed solvent).
Fractionation, followed by fractionation on a reverse-phase open column (eluent: mixed solvent of methanol / water), and reverse-phase HPL.
C fractionation (mobile phase: 50% acetonitrile, column: Shiseido Co., Ltd. CAPCELL PAK C18 UG120Å, detection: UV2
Compound 3 was isolated by 10 nm). Yield 11.3 mg, yield 0.002%.

The ¹³ C-NMR chemical shift values of Compound 3 are shown in Table 3 below. Chemical formula 8 shows the chemical structural formula corresponding to the carbon position number in Table 3. Compound 3 was identified as Cascumunarin B, a specific component of curcuminoids, by comparison with literature values.
Was identified.

[0020]

[Chemical 8]

[0021]

[Table 3]

Production Example 4 500 g of a rhizome of a crude fraction Zingiber purpureum Roxb. Containing Compounds 1 to 3 as active ingredients was ground, and immersed in ethanol at room temperature for 1 week for extraction. After the extract was filtered and concentrated, the concentrate was subjected to silica gel column chromatography (eluent: mixed system of n-hexane and ethyl acetate) to obtain 1.3 g of a crude fraction containing compounds 1 to 3.

The compounds 1 to 3 of the present invention have an excellent PAF antagonistic action and can be applied as a PAF antagonist for improving and preventing diseases and symptoms related to PAF. Also,
It can also be blended as an active ingredient of a skin external preparation for preventing and improving rough skin. PAF is one of the lipid mediators produced from the phospholipids of cell membranes by the action of metabolic enzymes such as phospholipase and acetyltransferase. In addition to epidermal cells, inflammatory cells such as mast cells, neutrophils and monocytes. Produced. It has been reported that PAF is involved in inflammation and allergic eosinophil migration, production of inflammatory cytokines, cell proliferation / differentiation, and apoptosis, and PAF antagonists antagonistically receive PAF. It is considered that by inhibiting the binding to the body, it exerts an effect on the improvement and prevention of diseases and symptoms involving PAF.

Further, it has been found that the compound according to the present invention also has a tyrosinase activity inhibitory action and an excellent melanin production inhibitory effect. Therefore, these are useful as whitening agents and can be applied to the skin to improve or prevent pigment abnormalities such as spots, freckles, chloasma, and freckles due to abnormal deposition of melanin pigment on the skin. Compound 1
Although 3 is a known substance, it has not been reported so far that they have an excellent PAF antagonism, and for the treatment of inflammatory / allergic skin diseases or skin roughening based on the PAF antagonism of these compounds. No application to external preparations is known at all. In addition, no effect on tyrosinase activity or melanin production has been reported. In the present invention, the compounding amount of the compounds 1 to 3 is 0.001 to 20.0% by mass, preferably 0.01 to 1 in the total amount of the external preparation.
It is 0.0 mass%. When it is less than 0.001% by mass,
The effect of the present invention is not sufficiently exerted, and 20.0% by mass
Even if the amount exceeds the above range, the increase of the effect cannot be expected substantially, and it tends to be difficult to add the effect to the external preparation for skin.

The external preparation for skin of the present invention contains, in addition to the above-mentioned essential components, components that are usually used in external preparations for skin such as cosmetics and pharmaceuticals, such as whitening agents, moisturizers, antioxidants, oily ingredients, and ultraviolet absorbers. , A surfactant, a thickener, alcohols, a powder component, a coloring material, an aqueous component, water, various skin nutrients and the like can be appropriately blended as necessary.

Other metal sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, citric acid, glycolic acid, lactic acid, salicylic acid, sodium sulfite, caffeine , Tannin, pantothenic acid and its derivatives, nicotinic acid and its derivatives, licorice extracts, various plant extracts such as glabridin, malonie, escin, vitamin E derivatives such as vitamin E and tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof Drug such as placenta extract, ascorbic acid and magnesium ascorbyl phosphate, ascorbic acid derivative such as glucoside ascorbate, arbutin, tranexamic acid, kojic acid, ellagic acid, chamomile oil, 4-n
-Whitening agents such as butylresorcinol, vitamin A derivatives such as vitamin A and retinol, sugars such as glucose, fructose, xylitol, mannose, sucrose, trehalose, moisturizers such as petrolatum, glycerin, urea, heparin, serine, arginine, etc. Various amino acids, lipids such as ceramide, cholesterol and the like can be appropriately added.

The external preparation for skin of the present invention refers to pharmaceuticals, quasi-drugs and cosmetics, and is used for conventional external preparations for skin such as ointments, creams, emulsions, lotions, packs, bath preparations and makeup cosmetics. The dosage form is not particularly limited as long as it is present. Hereinafter, the present invention will be described in more detail with reference to specific examples, but the present invention is not limited thereto. The blending amount is% by mass.

Test Example 1 PAF antagonistic activity test 1. Preparation of Sample As the test substance, the compound 1 obtained in the above Production Examples 1 to 4
~ 3 or crude fractions were used. These are respectively dissolved in dimethyl sulfoxide to prepare a 1% solution, a 0.5% solution,
A 0.25% solution was prepared and used as a sample for the test.

2. Test method The PAF antagonism was evaluated by the inhibitory effect on the platelet aggregation by PAF. Human blood was centrifuged at room temperature at 1100 rpm for 20 minutes to collect platelet rich plasma (PRP), and then further centrifuged at 3000 rpm for 5 minutes to collect platelet poor plasma (PPP). Add 223 μL of PRP to 37 ° C
After preliminarily heating in, the sample or solvent (D
MSO) was added in an amount of 2 μL, and the mixture was further incubated for 3 minutes at 37 ° C., and then 25 μL of an aggregation inducer PAF was added. The induced agglutination was measured using an aggregometer (manufactured by MCM Hemattracer MCM Medical Co., Ltd.), and the maximum agglutination rate of the test sample (the maximum value obtained from the agglutination curve of the test sample with the value of PPP being 100) was used. By comparing with the maximum aggregation rate of the solvent control, the PAF of the test substance
The inhibitory effect on the induced platelet aggregation was evaluated. The results are shown in Table 4.

[0030]

[Table 4]   ―――――――――――――――――――――――――――――――     Test substance Test substance concentration * (%) PAF-induced platelet aggregation inhibition rate (%)   ―――――――――――――――――――――――――――――――     Compound 1 0.008 84                     0.004 64                     0.002 25     Compound 2 0.008 86                     0.004 82                     0.002 64     Compound 3 0.0016 83                     0.0008 69                     0.0004 53                     0.0002 28     Coarse fraction 0.008 60                     0.004 38                     0.02 12   ―――――――――――――――――――――――――――――――   * Test substance concentration in reaction solution at the time of aggregation measurement

As can be seen from Table 4, compounds 1 to 1 of the present invention
3 has an excellent PAF antagonism.

Test Example 2 Actual Use Test The effect of improving rough skin (erythema / desquamation, dryness, eczema, itching), razor loss, and skin irritation were evaluated. 1. Using the compounds 1 to 3 and the crude fractions obtained in Sample Preparation Examples 1 to 4, lotions were prepared according to the formulations shown in Table 5, and the lotions were used as samples for the test. In addition, as a control, a lotion not containing these was prepared.

2. Test method (1) Rough skin improvement effect Using the faces of 70 women who suffer from rough skin, a sample is placed on one of the left and right cheeks and a control is placed on the other cheek twice a day.
After application for 2 weeks, the skin condition after that was visually determined, and the effect of improving rough skin was evaluated from the effectiveness rate. (Judgment Criteria for Improvement Effect on Skin Roughness) Remarkable Effect: Those in which the symptoms disappeared. Effective: Those with weakened symptoms. Slightly effective: The symptoms are slightly weakened. Invalid: No change in symptoms.

(Evaluation of rough skin improving effect) ⊚: The rate at which the test subject is markedly effective, effective and slightly effective (effective rate) is 80% or more. ◯: The rate (effective rate) at which the test subject is markedly effective, effective, and slightly effective (effective rate) is 50% to less than 80%. (Triangle | delta): The rate (effective rate) which a test subject shows remarkable, effective, and a little effective is 30% or more and less than 50%. X: The rate (effective rate) at which the subject is markedly effective, effective and slightly effective (effective rate) is less than 30%.

(2) Effects of improving razor loss Immediately after shaving, a sample or control lotion was applied to a panel of 70 males who lost razor, and the effect on razor loss was evaluated, and the razor loss was improved based on the effectiveness rate. The effect was evaluated. (Criteria for improvement effect on razor loss) Remarkable effect: razor loss disappeared. Effective: The razor loses its weakness. Slightly effective: The razor loses a little less. Invalid: No change in razor loss.

(Evaluation of Razor Loss Improvement Effect) ⊚: The rate at which the test subject is markedly effective, effective and slightly effective (effective rate) is 80% or more. ◯: The rate (effective rate) at which the test subject is markedly effective, effective, and slightly effective (effective rate) is 50% or more and less than 80%. (Triangle | delta): The rate (effective rate) which a test subject shows remarkable, effective, and a little effective is 30% or more and less than 50%. X: The rate (effective rate) at which the subject is markedly effective, effective and slightly effective (effective rate) is less than 30%.

(3) Skin irritation In the above-mentioned skin roughness improving effect test and razor loss improving effect test, skin irritation was evaluated according to the following criteria. ⊚: 0% of the subjects recognized tingling on the skin. ◯: Less than 5% of the subjects recognized tingling on the skin. Δ: Less than 10% of subjects had tingling sensations on the skin. X: 10% or more of the subjects have a tingling sensation on the skin.

[0038]

[Table 5]   ――――――――――――――――――――――――――――――――――         Ingredient Sample Control                       1 2 3 4 5 6 7   ――――――――――――――――――――――――――――――――――   Compound 1 0.5 0.2 − − − − − −   Compound 2 − − 0.5 0.2 − − − −   Compound 3 − − − − 0.5 0.2 − −   Coarse fraction − − − − − − 0.5 −   Glycerin 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0   1,3-Vitylene recall 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0   Ethanol 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0   Polyoxyethylene (20 mol)            Oleyl alcohol 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5   Purified water Residual Residual Residual Residual Residual Residual Residual   ――――――――――――――――――――――――――――――――――     Improvement effect on rough skin ◎ ○ ◎ ○ ◎ ◎ ○ △     Razor loss improvement effect ◎ ○ ◎ ○ ◎ ◎ ◎ ◎ △     Skin irritation ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ○   ――――――――――――――――――――――――――――――――――

As is clear from Table 5, the samples containing the compounds 1 to 3 or the crude fractions containing them as the active ingredient showed a better improving effect on rough skin and razor loss than the control, and skin irritation. The sex was not recognized either.

Test Example 3 Actual Use Test by Replica Method Using samples 1 to 7 of Test Example 2 and a control lotion, a rough skin improving effect test by a replica method was performed. That is, the skin surface morphology of a healthy female person (face) was sampled using a replica method and observed under a microscope (17 times). From the state of the skin pattern and the peeling state of the stratum corneum, 20 panels each (rough skin panel) judged to have a rough skin evaluation of 1 or 2 based on the criteria shown in Table 6 were used, and to the left and right half of the face,
Samples 1-7 and the control lotion were applied twice a day for 2 weeks. Two weeks later, the skin condition was observed again according to the above-mentioned replica method, and evaluated according to the criteria shown in Table 6. The results are shown in Table 7.

[0041]

[Table 6]   ―――――――――――――――――――――――――――――――――     Rating criteria Rating criteria   ―――――――――――――――――――――――――――――――――      1 Defects of skin clefts and cuticles, and wide-ranging horny layer of the stratum corneum are observed.      2 Unsmooth skin groove and crust, and horny turn of the stratum corneum.      3 There are pits and ridges, but they are flat.      4 Clear skin grooves and ridges.      5 Crusts and ridges are clear and well organized.   ―――――――――――――――――――――――――――――――――

[0042]

[Table 7]   ―――――――――――――――――――――――――――――――――     Replica evaluation Trial control                   1 2 3 4 5 6 7   ―――――――――――――――――――――――――――――――――         1 0 0 0 0 0 0 0 0 1         2 0 0 0 0 0 0 0 0 4         3 7 6 5 4 3 3 7 13         4 8 11 10 12 8 10 10 2         5 5 3 5 4 9 7 3 0   ―――――――――――――――――――――――――――――――――

As can be seen from Table 7, even in the replica method, the lotion of the present invention was compared with the control lotion,
A remarkable effect of improving rough skin was exhibited.

Test Example 4 Tyrosinase activity inhibitory effect and melanin production inhibitory effect B16 melanoma seeded on a 96-well microplate was cultured for 3 days in a culture medium (MEM + 10% FBS + theophylline) containing each concentration of compound 1 or compound 2. . Excluding the culture solution, 10 mM L-DOPA and 1%
PBS (pH 7.4) containing Triton-X 10
0 μL was added and reacted at 37 ° C. for 20 minutes. The absorbance at 475 nm was measured with a microplate reader before and after the reaction. The tyrosinase activity inhibition rate of each test compound in the cell line was calculated from the change in absorbance before and after the reaction. In addition, the melanin production inhibitory effect was evaluated by observing the plate with a microscope through a polarizing filter and evaluating in 3 grades (effect ++, moderate effect +, no effect −). The results are shown in Table 8. As can be seen from Table 8, Compounds 1 and 2 showed inhibitory effects on tyrosinase activity in cell lines even at low concentrations of 0.005 mM and 0.01 mM.
It was also excellent in the effect of suppressing melanin production. Therefore,
It is understood that these are very useful as whitening agents.

[0045]

[Table 8]   ―――――――――――――――――――――――――――――――――   Compound concentration (mM) Tyrosinase activity inhibitory rate (%) Melanin production inhibitory effect   ―――――――――――――――――――――――――――――――――   Compound 1 0.01 80 ++               0.005 55 +   ―――――――――――――――――――――――――――――――――   Compound 2 0.01 75 ++               0.005 30 +   ―――――――――――――――――――――――――――――――――

[0046]

Example 1 Cream (formulation) Stearic acid 5.0% by mass Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Compound 1 0.1 Caustic potash 0.1. 2 Sodium bisulfite 0.05 Preservative Suitable amount Perfume Suitable amount Ion-exchanged water Residual (production method) Dissolve propylene glycol and caustic potash in ion-exchanged water, heat and maintain at 70 ° C (water phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is maintained for a while to cause the reaction. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

Example 2 Cream (formulation) Stearic acid 5.0% by mass Sorbitan monostearate 2.5 Polyoxyethylene (20 mol) Sorbitan monostearate 1.5 Arbutin 7.0 Sodium bisulfite 0.03 Propylene glycol 10.0 Compound 2 0.05 Glycerin trioctanoate 10.0 Squalene 5.0 Octyl paradimethylaminobenzoate 3.0 Ethylenediaminetetraacetic acid disodium salt 0.01 Ethylparaben 0.3 Fragrance Ion exchange Water residue (production method) Ion-exchanged water is dissolved by adding propylene glycol and ethylenediaminetetraacetic acid disodium salt,
It was kept at 70 ° C (aqueous phase). Other ingredients were mixed and dissolved by heating to maintain 70 ° C (oil phase), the oil phase was gradually added to the aqueous phase, preliminarily emulsified at 70 ° C, homogenized with a homomixer, and then well mixed. While cooling to 30 ° C.

Example 3 Cream (formulation) Solid paraffin 5.0% by mass 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 Compound 1 0.05 Compound 2 0.05 Sodium bisulfite 0.03 Ethylparaben 0.3 Perfume Suitable amount Ion-exchanged water Residual (production method) Soap powder and borax in ion-exchanged water In addition, the mixture was heated and melted and maintained at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is 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 mass Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) Monooleate ester 2.0 Polyethylene glycol 1500 3. 0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (Brand name: Carbopol 941, BFGoodrich Chemical company) Compound 1 0.01 Sodium bisulfite 0.01 Ethylparaben 0.3 Fragrance 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 were added to the remaining ion-exchanged water, and the mixture was heated and dissolved and maintained at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase for preliminary emulsification, the phase A is added and the mixture is homogenized with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. while being well stirred.

Example 5 Emulsion (prescription) Microcrystalline wax 1.0% by mass 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 Compound 2 1.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Perfume Ion-exchanged water Residual (production method) Add propylene glycol to ion-exchanged water,
Heat to maintain 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added to this and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C while stirring well.

Example 6 Jelly (formulation) 95% ethyl alcohol 10.0 mass% 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 Compound 1 5.0 2-Hydroxy-4-methoxy benzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate.3 sodium.2 water 0.05 Methylparaben 0. 2 Perfume A suitable amount Ion-exchanged water Residual (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while Compound 1 and polyoxyethylene (50 mol) oleyl alcohol ether are dissolved in 95% ethanol and added to the aqueous phase. To do. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 7 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Mass Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Compound 2 2. 0 Methylparaben 0.15 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 (trade name: Carbopol 940, BFGoodrich Chemical company) Purified water Residual (manufacturing method) Dissolve Phases A and C uniformly, and add A to Phase C
Add phase and solubilize. Next, phase B is added and then filling is performed.

Example 8 Pack (formulation) (Phase A) Dipropylene glycol 5.0% by mass Polyoxyethylene (60 mol) Hardened castor oil 5.0 (Phase B) Compound 3 0.05 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 Residue (production method) A Phase, B phase, and C phase are dissolved uniformly,
Phase B is added to the phase to solubilize it. Next, this is added to phase C and then filled.

Example 9 Solid foundation (formulation) Talc 43.1% by mass 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 compound 2 0.5 preservative proper amount perfume proper amount (production method) Talc to black iron oxide powder components are sufficiently mixed with a blender, and Squalane-isocetyl octoate oil component, compound 2, preservative, and fragrance are well kneaded, then filled into a container and molded.

Example 10 Emulsion type foundation (cream type) (Formulation) (Powder part) Titanium dioxide 10.3% by mass 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 Compound 1 0.5 (Aqueous phase) Purified water 50.0 1,3-Butyrene gul Cole 4.5 Sorbitan sesquioleate 3.0 Preservative proper amount Perfume proper amount (manufacturing method) After heating and stirring the aqueous phase, a powder portion thoroughly mixed and pulverized is added and treated with a homomixer. Further, the heated and mixed oil phase is added, and the mixture is treated with a homomixer. Then, the fragrance is added with stirring and the mixture is cooled to room temperature.

Example 11 Cream (prescription) Stearic acid 5.0% by mass Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Compound 2 0.01 Caustic potash 0.2 Sodium bisulfite 0.01 Preservative Suitable amount Perfume Suitable amount Ion-exchanged water Residual (production method) Add propylene glycol and caustic potash to ion-exchanged water, dissolve and heat to 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 the reaction. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

Example 12 Cream A cream was prepared in the same manner as in Example 2 according to the following formulation. Stearic acid 6.5 Sorbitan monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan monostearate 1.5 Propylene glycol 10.0 Compound 1 0.05 Glycerin trioctanoate 10.0 Squalene 5.0 Sodium hyaluronate 1.0 Ethylenediaminetetraacetic acid trisodium salt 0.01 Glucose 0.5 Ascorbic acid glucoside 5.0 Ethylparaben 0.3 Fragrance Suitable amount Ion-exchanged water Residue (production method) Ion-exchanged water with propylene glycol and ethylenediaminetetraacetic acid Add trisodium acetate salt to dissolve,
It was kept at 70 ° C (aqueous phase). Other ingredients are mixed and dissolved by heating and maintained at 70 ° C (oil phase), the oil phase is gradually added to the aqueous phase, preliminarily emulsified at 70 ° C, homogenized with a homomixer, and then well mixed. While cooling to 30 ° C.

Example 13 Cream (formulation) Solid paraffin 5.0% by mass 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 Compound 1 1.0 Compound 2 1.0 Sodium bisulfite 0.03 Ethylparaben 0.3 Fragrance Suitable amount Ion-exchanged water Residual (production method) Soap powder and borax in ion-exchanged water In addition, the mixture was heated and melted and maintained at 70 ° C. (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is 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.

[0059] Example 14 Emulsion A: Oil phase   Squalane 5.0 mass%   Oleyl oleate 3.0   Vaseline 2.0   Sorbitan sesquioleate 0.8   Polyoxyethylene     Oleyl ether (20EO) 1.2   Compound 2 0.01   Evening primrose oil 0.5   Fragrance 0.3   Preservative Appropriate amount B: Water phase   1,3-butylene glycol 4.5   Maltitol 4.0   Ethanol 3.0   Carboxy vinyl polymer 0.2   Potassium hydroxide 0.1   L-arginine L-aspartate 0.01   Serine 0.05   Purified water balance (Production method) An emulsion was obtained by a conventional method.

Example 15 Emulsion (formulation) Microcrystalline wax 1.0% by mass 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 Compound 1 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 to maintain 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added to this and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C while stirring well.

Example 16 Jelly (formulation) 95% ethyl alcohol 10.0 mass% 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 Compound 3 7.0 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate / 3 sodium / diwater 0.05 Methylparaben 0 .2 Fragrance A suitable amount of ion-exchanged water Residual (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while Compound 3 and polyoxyethylene (50 mol) oleyl alcohol ether are dissolved in 95% ethanol to form an aqueous phase. Added. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 17 Serum (1) Compound 1 2.0% by mass (2) Concentrated glycerin 30.0 (3) 1,3-butylene glycol 20.0 (4) Propylene glycol 20.0 (5) Polyethylene Glycol 400 15.0 (6) Polyoxyethylene (60) Hydrogenated castor oil 5.0 (7) Squalane 2.0 (8) Liquid paraffin 3.0 (9) Perfume 0.1 (10) Purified water Residual ( (Manufacturing method) (1)-(5) and (10) were mixed, and heat-dissolved (6), (7), (8) and (9) were mixed with stirring to obtain a beauty essence.

Example 18 Pack (1) Polyvinyl alcohol 10.0% by mass (2) Polyethylene glycol (molecular weight 400) 0.4 (3) Glycerin 3.0 (4) Ethanol (95%) 8.0 (5) Compound 1 3.0 (6) Compound 2 3.0 (7) Preservative 0.1 (8) Perfume 0.1 (9) Purified water Residual (manufacturing method) At room temperature, (4), (5), (6), (7),
(8) was mixed and dissolved, and (1), (2), (3) and (9) were mixed and dissolved at 80 ° C., and the mixture was stirred and added, and then allowed to cool to room temperature to obtain a pack.

Example 19 Solid foundation (formulation) Talc 43.1% by mass 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 compound 3 0.5 preservative appropriate amount perfume appropriate amount (production method) Talc to black iron oxide powder components are sufficiently mixed with a blender, and Squalane-isocetyl octoate oil component, compound 3, preservative, and fragrance are well kneaded, then filled into a container and molded.

Example 20 Emulsion type foundation (cream type) (formulation) (powder part) titanium dioxide 10.3 mass% sericite 5.4 kaolin 3.0 yellow iron oxide 0.8 red iron oxide 0.3 black iron oxide 0.2 (Oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 Compound 2 1.5 (Aqueous phase) Purified water 50.0 1,3-Butyrene gul Cole 4.5 Sorbitan sesquioleate 3.0 Preservative proper amount Perfume proper amount (manufacturing method) After heating and stirring the aqueous phase, a powder portion thoroughly mixed and pulverized is added and treated with a homomixer. Further, the heated and mixed oil phase is added, and the mixture is treated with a homomixer. Then, the fragrance is added with stirring and the mixture is cooled to room temperature.

Example 21 Cream A: Oil phase Stearic acid 10.0% by mass Stearyl alcohol 4.0 Butyl stearate 8.0 Stearic acid monoglycerin ester 2.0 Vitamin E acetate 0.5 Vitamin A palmitate 0.1 Crude Fraction 0.5 Macadamia nut oil 1.0 Fragrance 0.4 Preservative Appropriate amount B: Aqueous phase Glycerin 4.0 1,2-Pentanediol 3.0 Potassium hydroxide 0.4 Magnesium ascorbyl phosphate 0.1 Tranexam Acid 0.05 Trisodium edetate 0.05 Purified water Residue (production method) The oil phase part of A and the water phase part of B are heated to 70 ° C. to completely dissolve them. Phase A is added to phase B and emulsified with an emulsifier. The emulsion was cooled using a heat exchanger to obtain a cream.

Example 22 Emulsion (formulation) Stearic acid 2.5% by mass Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) Monooleate ester 2.0 Polyethylene glycol 1500 3. 0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (Brand name: Carbopol 941, BFGoodrich Chemical company) Crude fraction 1.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Perfume Suitable amount Ion-exchanged water Residual (manufacturing method) ) Dissolve carboxyvinyl polymer in a small amount of ion-exchanged water (Phase A). Polyethylene glycol 1500 and triethanolamine were added to the remaining ion-exchanged water, and the mixture was heated and dissolved and maintained at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase for preliminary emulsification, the phase A is added and the mixture is homogenized with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. while being well stirred.

Example 23 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Mass Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Crude Fraction 2 0.0 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) Dissolve Phases A and C uniformly,
Add phase and solubilize. Next, phase B is added and then filling is performed.

Example 24 Pack (formulation) (Phase A) Dipropylene glycol 5.0% by mass Polyoxyethylene (60 mol) Hydrogenated castor oil 5.0 (Phase B) Crude fraction 5.0 Olive oil 5.0 Acetic acid Tocopherol 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 (production method) A phase, B phase, and C phase are uniformly dissolved,
Phase B is added to the phase to solubilize it. Next, this is added to phase C and then filled.

Example 25 Solid Foundation (Formulation) Talc 43.1% by mass 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 crude fraction 1.0 preservative appropriate amount perfume appropriate amount (production method) Talc to black iron oxide powder components are thoroughly mixed with a blender, To this, an oily component of squalane to isocetyl octoate, a crude fraction, an antiseptic and a fragrance are added and kneaded well, then filled into a container and molded.

Example 26 Emulsion type foundation (cream type) (Prescription) (Powder part) Titanium dioxide 10.3% by mass 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 crude fraction 2.0 (water phase) purified water 50.0 1,3-butylene Glucol 4.5 Sorbitan sesquioleate 3.0 Preservative Suitable amount Perfume Suitable 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 heated and mixed oil phase is added, and the mixture is treated with a homomixer. Then, the fragrance is added with stirring and the mixture is cooled to room temperature.

Example 27 Jelly (formulation) 95% ethyl alcohol 10.0 mass% 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 Crude fraction 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 Residual (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while crude fraction, polyoxyethylene (50 mol) oleyl alcohol ether is dissolved in 95% ethanol, and water is added. Add to phase. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 28 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Mass Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Crude Fraction 3 0.0 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) Dissolve Phases A and C uniformly,
Add phase and solubilize. Next, phase B is added and then filling is performed.

Example 29 Pack (formulation) (Phase A) Dipropylene glycol 5.0% by mass Polyoxyethylene (60 mol) Hardened castor oil 5.0 Crude fraction 5.0 (Phase B) Olive oil 5.0 Acetic acid Tocopherol 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 (production method) A phase, B phase, and C phase are uniformly dissolved,
Phase B is added to the phase to solubilize it. Next, this is added to phase C and then filled.

Example 30 Lotion (1) Compound 1 0.05% by mass (2) Aspartic acid 1.0 (3) Tocopherol acetate 0.01 (4) Glycerin 4.0 (5) 1,3-Butylene glycol 4.0 (6) Ethanol 8.0 (7) Polyoxyethylene (60) Castor oil 0.5 (8) Methylparaben 0.2 (9) Citric acid 0.05 (10) Sodium citrate 0.1 ( 11) Fragrance 0.05 (12) Purified water (2), (4), (5), (9) and (10) were dissolved in the residue (production method) (12) to give a purified aqueous solution. Separately, (6)
(1), (3), (7), (8), and (11) were dissolved in, and this was added to the above-mentioned purified aqueous solution for solubilization and filtered to obtain a lotion.

Example 31 Lotion A: Alcohol phase Ethanol 5.0 wt% POE oleyl alcohol ether 2.0 2-Ethylhexyl-P-dimethylaminobenzoate 0.18 Compound 2 0.1 Perfume 0.05 B: Water phase 1,3 Butylene glycol 9.5 Sodium pyrrolidonecarboxylate 0.5 Whey extract 5.0 Nicotinic acid amide 0.3 Glycerin 5.0 Hydroxypropyl β cyclodextrin 1.0 Ethylenediaminehydroxyethyl 3 sodium acetate 1.0 Lysine 0.05 Tranexamic acid 1.0 Purified water Residue (manufacturing method) The alcohol phase of A was added to the aqueous phase of B and solubilized to obtain lotion.

Example 32 Lotion A: Alcohol phase Ethanol 5.0% by mass POE Oleyl alcohol ether 2.0 2-Ethylhexyl-P-dimethylaminobenzoate 0.18 Perfume 0.05 B: Water phase 1,3 Butylene glycol 9.5 Sodium pyrrolidonecarboxylate 0.5 Whey extract 5.0 Nicotinamide 0.3 Glycerin 5.0 Trimethylglycine 3.0 Crude fraction 1.0 Hydroxypropyl β cyclodextrin 1.0 Ethylenediaminehydroxyethyl 3 Trisodium acetate 1.0 Lysine 0.05 Tranexamic acid 1.0 Purified water Residual (manufacturing method) The alcohol phase of A was added to the aqueous phase of B to be solubilized to obtain a lotion.

Example 33 Emulsion foundation A: Oil phase compound 1 0.1% by mass Compound 2 0.1 Cetanol 3.5 Deodorizing lanolin 4.0 Jojoba oil 5.0 Vaseline 2.0 Squalane 6.0 Monoglycerin stearate Ester 2.5 POE (60) hydrogenated castor oil 1.5 POE (20) cetyl ether 1.0 pyridoxine tripalmitate 0.1 preservative appropriate amount perfume 0.3 B: aqueous phase propylene glycol 10.0 whey 0 .1 Formulated powder 12.0 Histidine 5.0 Purified water Residual (production method) The oil phase part of A and the water phase part of B are heated to 70 ° C. to completely dissolve them. Phase A is added to phase B and emulsified with an emulsifier. The emulsion was cooled using a heat exchanger to obtain an emulsion foundation.

[0079]

As described above, the compound 1 of the present invention
Nos. 3 to 3 are excellent in PAF antagonistic action, and by blending them, it is possible to obtain an external preparation for skin having excellent effects in improving and preventing various skin diseases, rough skin, etc. Further, since it also has a tyrosinase activity inhibitory action and a melanin production inhibitory action, it can exert a whitening effect.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 7/00 A61K 7/00 R U X 7/021 7/021 31/09 31/09 31/12 31 / 12 35/78 35/78 C X A61P 7/02 A61P 7/02 17/04 17/04 17/16 17/16 37/08 37/08 43/00 111 43/00 111 (72) Inventor Maeda Noriju, 2-1, 1-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa Prefecture F-term in the Shiseido Research Center (Shin-Yokohama) (reference) 4C083 AA072 AA082 AA111 AA112 AA122 AB032 AB152 AB212 AB232 AB242 AB352 AB432 AB442 AC012 AC022 AC072 AC102 AC112 AC122 AC132 AC171 AC172 AC182 AC211 AC212 AC242 AC262 AC352 AC422 AC432 AC442 AC482 AC532 AC552 AC582 AC622 AC642 AC742 AC792 AC852 AD042 AD092 AD112 AD162 AD172 AD202 AD332 AD392 AD412 AD512 AD642 AD662 BB51 CC04 CC05 CC07 CC21 DD22 DD23 DD27 DD31 DD41 EE12 EE13 EE16 FF01 FF05 4C088 AB81 AC01 AC11 AC13 BA08 BA09 BA10 BA23 BA32 CA05 CA06 CA07 CA08 CA14 MA02 MA03 MA04 MA17 MA22 MA28 MA63 NA14 ZA89 ZB13 ZC20 4C206 AA01 AA02 CA34 CB19 KA13 ZA01 MA01 MA17 KA01 KA14 MA17 MA18 KA01 ZA14 MA17 MA18

Claims (8)

[Claims] 1. A skin external preparation containing at least one of the following compounds 1 to 3 as an active ingredient. [Chemical 1] [Chemical 2] [Chemical 3] 2. The external preparation for skin according to claim 1, wherein an extract of a ginger plant of the ginger family Ginger is contained as an active ingredient in the external preparation of claim 1. 3. The external preparation according to claim 1 or 2, wherein
An external preparation for skin, wherein at least one of the compounds 1 to 3 or an extract of a ginger plant of the genus Ginger genus containing the same is a rough skin improving agent. 4. A platelet activating factor antagonist comprising at least one of the compounds 1 to 3 as an active ingredient. 5. The platelet activating factor antagonist according to claim 3, wherein an extract of a ginger plant of the genus Ginger family containing at least one of the compounds 1 to 3 as an active ingredient is blended. . 6. A tyrosinase activity inhibitor containing at least one of the compounds 1 and 2 as an active ingredient. 7. The tyrosinase activity inhibitor according to claim 6, wherein an extract of a ginger genus Ginger plant containing at least one of the compounds 1 and 2 as an active ingredient is blended. 8. A whitening agent containing the tyrosinase activity inhibitor according to claim 6 or 7 as an active ingredient.