WO2003090708A1

WO2003090708A1 - External preparation for skin

Info

Publication number: WO2003090708A1
Application number: PCT/JP2003/005217
Authority: WO
Inventors: Masahiro Ota; Kazuhisa Maeda
Original assignee: Shiseido Co., Ltd.
Priority date: 2002-04-23
Filing date: 2003-04-23
Publication date: 2003-11-06
Also published as: JP4762477B2; JP2003313116A; TW200306857A

Abstract

External preparations for skin comprising a substance exhibiting high antagonism to platelet activating factor (PAF) and being effective in skin disorder amelioration and prevention and a substance capable of exerting a tyrosinase activity inhibiting effect as active ingredients. In particular, at least one of the following compounds (1) to (3) is contained as an active ingredient.

Description

Description Skin external preparation This application claims the priority of Japanese Patent Application No. 2000-2012, filed on April 23, 2012, and is hereby incorporated by reference. It is folded.

[Technical field]

The present invention relates to a skin external preparation, particularly to an active ingredient thereof.

[Background technology]

Conventionally, the effective ingredients of skin external preparations that have the effect of improving / preventing skin roughness due to skin diseases such as atopic dermatitis, contact dermatitis, eczema, and psoriasis and rough and rough skin of healthy persons include: Steroids with anti-inflammatory effects: Vaseline, urea, heparin, various amino acids, and lipids with moisturizing action have been used.

However, steroids have strong side effects, and moisturizers are not always effective enough, and the development of safer and superior active ingredients has been desired.

In recent years, it has been clarified that platelet activating factor (hereinafter, referred to as PAF) is involved in the development of various inflammatory allergic skin diseases and rough skin. For example, in psoriasis, which is an inflammatory dyskeratosis, high PAF is found 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 thought to play an important role in the normal keratinization process of the epidermis such as keratinization, and attempts are being made to use PAF antagonists as drugs for improving skin roughness or treating skin diseases. It is becoming.

On the other hand, skin external preparations are also required to have functions other than improving skin roughness, and whitening agents are used to whiten pigmentation such as spots, freckles, and liver spots caused by abnormal deposition of melanin pigment. ing. Vitamin C and its derivatives, kojic acid, arbutin, etc. are known as whitening agents, and these are tyrosiners indispensable for melanin production. By inhibiting the activity of ze, the production of melanin is suppressed. However, these effects have not yet been sufficiently effective.

[Disclosure of the Invention]

The present invention has been made in view of the above-mentioned problems of the prior art, and one of its objects is to have excellent PAF antagonism, and to improve inflammatory and allergic skin diseases and rough skin of healthy people. And a PAF antagonist and an external preparation for skin containing the same as an active ingredient. Another object is to provide a substance having an excellent tyrosinase activity inhibitory action, inhibiting melanin production and exerting a whitening effect, and an external preparation for skin containing the same.

As a result of intensive studies by the present inventors to achieve the above object, certain methoxybenzene derivatives and a specific component of talcuminide, Cassumunarin B, have an excellent PAF antagonistic action, and these compounds have erythema, desquamation, It has been found to improve rough skin with dryness, eczema, itching, etc. Further, as a result of further study, they have also found that they have a tyrosinase activity inhibitory activity and suppress melanin production, and have completed the present invention. That is, the skin external preparation of the present invention is characterized by containing at least one of the following compounds 1 to 3 as an active ingredient.

In the external preparation of the present invention, it is preferable to blend an extract of the genus Zingiberaceae, which contains at least one of the compounds 1 to 3 as an active ingredient.

In the external preparation of the present invention, it is preferable that at least one of the compounds 1 to 3 or an extract of a plant belonging to the genus Zingiberaceae belonging to the genus Zingiberaceae is a skin roughness improving agent. Further, the platelet activating factor antagonist of the present invention comprises at least one of the compounds 1 to 3. It is characterized by containing as an active ingredient.

In the antagonist of the present invention, it is preferable to add an extract of a plant belonging to the genus Zingiberaceae, which includes at least one of the compounds 1 to 3 as an active ingredient.

Further, the tyrosinase activity inhibitor of the present invention is characterized by containing at least one of the compounds 1 to 2 as an active ingredient.

In the inhibitor of the present invention, it is preferable to add an extract of a plant belonging to the genus Zingiberaceae, which includes at least one of the compounds 1 to 2 as an active ingredient.

Further, the whitening agent according to the present invention is characterized by containing the tyrosinase activity inhibitor as an active ingredient.

[Best Mode for Carrying Out the Invention]

Compounds 1-3 according to the present invention can be isolated from plants using known methods. For example, compounds 1 and 2 are described in Phytochemistry, vol. 32, No. 2, p357-363, 1993 (author: Akiko Jitoe, Toshiya Masuda, and Nobuji Nakatani), and compound 3 is described in JAOCS, vol. 72, No. 9, p. 1053, 1995 (author: Toshiya Masuda, et. a 1.).

Examples of plants include plants of the family Zingiberaceae and the genus Zingiber. Examples of the ginger plants belonging to the genus Ginger, include ginger and ginger. Penguin power S grows naturally in tropical regions such as Okibashi and Southeast Asia, and its scientific name is Zingiber purpure um Roxb. Synonym).

The site to be used is not particularly limited as long as compounds 1 to 3 can be obtained. Examples thereof include roots, rhizomes, stems, leaves, flowers, fruits, whole plants, and the like, and preferably roots or rhizomes. To give a specific example, pulverized ginger root or rhizome is extracted by immersion in an extraction solvent at room temperature to under heating, and this extract is purified by column separation purification, recrystallization, etc. You can get 3.

The extraction solvent is not particularly restricted but includes, for example, primary alcohols such as water, methanol and ethanol, and polyhydric alcohols such as 1,3-butylene glycol and propylene glycol. And lower alkyl esters such as ethyl and ethyl acetate; hydrocarbons such as benzene and hexane; ethyl ether; acetone; and the like. Two or more of these can be used in combination. Preferred extraction solvents include water, methanol, ethanol, 1,3-butylendacol, or a mixed solvent thereof.

In the present invention, in addition to the compounds 1 to 3, an extract containing these as an active ingredient can also be used. Examples of such an extract include a primary extract extracted with the above-mentioned extraction solvent, and a crude fraction obtained by roughly purifying the primary extract by silica gel chromatography or the like.

In addition, as the compounds 1 to 3 of the present invention, in addition to those extracted from natural products, it is also possible to use 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 an active ingredient is shown below. Production Example 1 Isolation of Compound 1

500 g of rhizomes of Zingiber purpureum Roxb. Were ground, immersed in 2.5 L of methanol for 1 week at room temperature, and extracted. After the extract was filtered and concentrated, the concentrate was subjected to silica gel column chromatography (eluent: a mixed system of n-hexane and ethyl acetate) to obtain a crude fraction. Further, the compound was subjected to reverse phase HPLC preparative analysis (mobile phase: 60% acetone nitrile, column: CAPSELLPAK C18 UG120A manufactured by Shiseido Co., Ltd., column size: 1 1ιηπι φ X 25 O mm, detection: UV 210 nm). 1 was isolated. Yield 410mg, yield 0.02%. Table shows the chemical shift values of ^{1 3} C-NMR of Compound 1 with literature values to 1. Also, FIG. 7 shows a chemical structural formula corresponding to the carbon position No. in Table 1.

¹³ CNMR—Chemical shift (solvent:: CdCl -d) Carbon position number Compound 1 Literature *

1 127.64 127.6

2 130.33 130.3

3 48.10 48.1

4 45.47 45.4

5 27.91 27.8

6 24.58 24.5

1 '137.66 137.6

2 '111.80 111.9

3, 147.43 147.5

4, 148.35 148.4

5, 110.96 111.1

6 '120.50 120.5

1 "132.26 132.2 2〃 128.94 128.9

', 131.07 131.1

2 '"108.81 108.9

3 '"148.67 148.7

0 0

4 '"149.02 149.0

5 '"111.26 111.3

6 118.86 118.8

55.90 55.9

OMe 56.01

*: Jiteo, A., Masuda, T., Nakatani, N.,

Phytochemistry, vol.32 No.2 P357-363 (1993) Production Example 2 Isolation of Compound 2

500 g of rhizome of Zingiber purpureura Roxb. Was pulverized, immersed in 2.5 L of methanol at room temperature for 1 week, and extracted. After the extract was filtered and concentrated, the concentrate was subjected to silica gel column chromatography (eluent: a mixture of n-hexane and ethyl acetate) to obtain a crude fraction. Further, Compound 2 was isolated by reverse phase HPLC preparative (mobile phase: 60% acetonitrile, column: CAPSELLPAK C18 UG120A manufactured by Shiseido Co., Ltd., column size: 1 1ηπιφX 25 Omm, detection: UV2 10 nm). . Yield 430mg, Yield 0.086%. Table 2 shows the chemical shift values of 1 ³ C-NMR of Compound 2 with literature values. In addition, the carbon position numbers in Table 2 conform to the above-mentioned Chemical Formula 7.

¹³ CNMR—Chemical shift (solvent: CdCl -d)

Carbon position number Compound 2 Literature *

Q

40. ί 丄 40. O

4 e

^: 4.0,

Ό .0

a

OA

1,

丄 Top, ο Dimension 丄 y. Y

Q Q

Δ 丄丄 ΟΌ 丄丄 o

0 丄 4 DO 丄 4 β D

4 14ο. 丄

0 110.42 丄丄 ί

Ό 122.02 丄 υ

丄 132.53 丄《5 n 4

Ge '128.57 丄 οο.0

〃,

丄丄《丄.

) 〃, 108.76

3 '"148.30 148.3

A "'149.00 AQ 0

5 '"111.23 111.3

6 118.81 118.8

55.84 55.8

OMe 55.94 55.9

*: Jiteo, A., Masuda, T., Nakatani, N.,

Phytochemistry, vol.32 No.2 P357-363 (1993) Production Example 3 Isolation of Compound 3

509.7 g of rhizome of Zingiber purpureura Roxb. Was pulverized, immersed in 2.5 L of methanol for 1 week at room temperature, and extracted. After filtering and concentrating the extract, concentrate the concentrate on a silica gel column.

(Eluent: n-hexane / ethyl acetate mixed solvent), then fractionation on a reversed-phase open column (eluent: methanol / water mixed solvent), followed by reversed-phase HPLC fractionation (Mobile phase: 50% acetonitrile, Column: CAPCELL PAK C18 UG120A manufactured by Shiseido Co., Ltd., Detection: UV21 O nm) to isolate Compound 3. Yield 11.3 mg, Yield 0.002% _c The ¹³ C-NMR chemical shift value of Compound 3 is shown in Table 3 below. Formula 8 shows the chemical structural formula corresponding to the carbon position number in Table 3. Compound 3 was identified as a specific component of curcuminoid, Cassumun arin B, by comparison with literature values. Chemical 8

Table 3

¹³ CNMR—Chemical shift (solvent: CdCl _a -d)

Carbon position number Compound 3 Literature *

1 35.8 35.8

2 36.2 36.2

3 44.8 44.8

4 54.7 54.7 5 55.8 (CX 2) 55.8 (CX 2)

6 55. 9 (C X 2) 56.0 (C X 2)

7 102. 0 102. 0

8 109. 5 109. 6

9 110. 1 110. 1

1 0 110.5 110.6

1 1 113. 2 113. 2

1 2 114. 2 114. 3

1 3 114. 7 114. 8

1 4 119. 8 119. 8

1 5 120. 4 120. 4

1 6 121. 7 121. 7

1 7 122.5 122.5

1 8 127. 3 127. 3

1 9 127. 7 127. 7

2 0 128. 3 128. 3

2 1 132. 2 132. 2

2 2 137.1 137.1

2 3 139. 4 139. 5

2 4 143. 8 143. 8

2 5 146. 3 146. 4

2 6 146. 7 146. 7

2 7 147.6 丄 47.6

2 8 148.0 148.0

2 9 148.3 148.3

3 0 176.5 5 176.5

3 1 200.5 200.5

* Masuda et al., JAOCS, Vol. 72, No. 9, pl053- 1057 (1995) Production Example 4 Crude fraction containing compounds 1 to 3 as active ingredients

500 g of rhizome of Zingiber purpureura Roxb. Was pulverized, immersed in ethanol at room temperature for 1 week, and extracted. After the extract was filtered and concentrated, the concentrate was subjected to silica gel column chromatography (eluent: a mixture 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 antagonism and can be applied as a PAF antagonist for ameliorating or preventing diseases and symptoms associated with PAF. It can also be used as an active ingredient in skin preparations for preventing and improving rough skin.

PAF is one of the lipid mediators produced by the action of metabolic enzymes such as phospholipase acetyltransferase from the phospholipids of the cell membrane.In addition to epidermal cells, inflammatory cells such as mast cells, neutrophils and monocytes Produced in PAF has been reported to be involved in inflammation and allergic eosinophil migration, inflammatory site force production, cell proliferation / differentiation, and apoptosis.PAF antagonists are antagonistic to PAF By inhibiting its binding to its receptor, it is thought to be effective in ameliorating or preventing diseases and symptoms associated with PAF.

In addition, it has been found that the compounds according to the present invention also have a tyrosinase activity inhibitory effect and are excellent in a melanin production inhibitory effect. Therefore, they are useful as whitening agents, and can be applied to the skin to improve and prevent pigment abnormalities such as spots, freckles, liver spots and sparrow eggs caused by abnormal deposition of melanin pigment on the skin.

Compounds 1 to 3 are known substances, but they have not been reported to have an excellent PAF antagonistic action.Furthermore, inflammatory and allergic skin based on the PAF antagonistic action of these compounds has not been reported. There is no known application to a drug for treating a disease or an external preparation for improving rough skin. In addition, no report has been made on the tyrosinase activity inhibitory effect or melanin production inhibitory effect.

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 10.0% by mass in the total amount of the external preparation. If the amount is less than 0.001% by mass, the effect of the present invention is not sufficiently exerted. Even if the amount is more than 20.0% by mass, the effect cannot be substantially increased, and the addition to a skin external preparation is not expected. Also tend to be difficult. In addition to the above-mentioned essential components, the skin external preparation of the present invention includes components usually used in skin external preparations such as cosmetics and pharmaceuticals, for example, whitening agents, moisturizing agents, antioxidants, oily components, ultraviolet absorbers, and surfactants. Agents, thickeners, alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients, and the like can be appropriately compounded as necessary.

In addition, sequestering agents such as disodium edetate, sodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, dalconic acid, cunic acid, glycolic acid, lactic acid, salicylic acid, sodium sulfite, caffeine, tannin , Pantothenic acid and its derivatives, nicotinic acid and its derivatives, licorice extract, various plant extracts such as glabridin, marronnier, escin, vitamin E derivatives such as vitamin E and tocopherol acetate, glycyrrhizic acid and its derivatives or Drugs such as salts, placenta extract, ascorbic acid derivatives such as ascorbic acid and magnesium phosphate ascorbate, darcoside ascorbate, arbutin, tranexamic acid, kojic acid, ellagic acid, potato oil, 4-n-butyl Whitening agents such as solcinol, vitamin A derivatives such as vitamin A and retinol, sugars such as glucose, fructose, xylitol, mannose, sucrose, and trehalose; humectants such as vaseline, glycerin, urea, and heparin; Various amino acids, such as serine and arginine, and lipids, such as ceramide and cholesterol, can also be appropriately compounded.

The skin external preparation of the present invention refers to pharmaceuticals, quasi-drugs, and cosmetics, for example, ointments, talmes, emulsions, lotions, packs, bath preparations, make-up cosmetics, and other conventional skin preparations There is no particular limitation on the dosage form.

Hereinafter, the present invention will be described in more detail by way of specific examples, but the present invention is not limited thereto. The compounding amount is mass%. Test Example 1 P AF antagonistic effect test

1. Sample preparation

As test substances, compounds 1-3 or crude fractions obtained in Production Examples 1-4 above were used. These were each dissolved in dimethyl sulfoxide to prepare a 1% solution, a 0.5% solution, and a 0.25% solution, which were used as samples for the test. 2. Test method

PAF antagonism was evaluated by its inhibitory effect on platelet aggregation by PAF.

Human blood was centrifuged at room temperature at 1100 rpm for 20 minutes to collect platelet-rich plasma (PRP), followed by centrifugation at 3000 rpm for 5 minutes to separate platelet-poor plasma (PPP). After pre-warming 223 μl of PRP at 37 ° C, add 2 / L of a sample or a solvent (DMSO) at a specified concentration, incubate at 37 ° C for 3 minutes, and then agglutinator P AF Was added with 25 μL.

The induced agglutination was measured using an aggregometer (MCM Hematrecer MCM Medical Co., Ltd.), and the maximum agglutination rate of the test sample (maximum obtained from the agglutination curve of the test sample with the value of Ρ Ρ 100 being 100) ) Was compared with the maximum aggregation rate of the solvent control to evaluate the inhibitory effect of the test substance on PAF-induced platelet aggregation. The results are shown in Table 4. Table 4 Test substance Test substance concentration * (%) PAF-induced inhibition of platelet aggregation (%) Compound 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

* Concentration of test substance in reaction solution at the time of agglutination measurement As can be seen from Table 4, compounds 1 to 3 of the present invention have excellent PAF antagonism. Test example 2 Actual use test

The effects of improving skin irritation (erythema and desquamation, dryness, eczema, itching) and losing power razors, and skin irritation were evaluated.

1. Fee

A lotion was prepared according to the formulation shown in Table 5 using the compounds 1-3 and the crude fraction obtained in Production Examples 1-4, and this was used as a sample for the test. As a control, a lotion not containing these was prepared.

2. Test method

(1) Skin roughness improvement effect

70 Use the face of a female panel of 0 women, apply the sample to one of the right and left 頰, and apply the control to the other 2 twice a day for 2 weeks, and then visually check the skin condition The efficiency of skin roughness was evaluated based on the efficiency.

(Criteria for improvement effect on rough skin)

Significantly effective: those with disappeared symptoms.

Effective: those with weakened symptoms.

Somewhat effective: Slightly weakened symptoms.

Ineffective: No change in symptoms.

(Evaluation of skin roughness improvement effect)

:: The proportion (effective rate) at which the subject showed a marked effect, an effect and a slight effect was 80% or more.

〇: The proportion (effective rate) at which the subject shows a markedly effective, effective, or slightly effective (effective rate) is 50% or more to less than 80%. Δ: The proportion (effective rate) at which the test subjects showed remarkable, effective, and somewhat effective was 30% or more and less than 50%.

X: The proportion (effective rate) at which the subject showed significant, effective, and somewhat effective was less than 30%.

(2) Improvement of losing force

Immediately after shaving, a sample or control mouthpiece was applied to 70 male panels losing force razors, the effect on losing force razors was determined, and the effect of losing force razors was evaluated from the effectiveness rate.

(Criteria for improvement effect against loss of force razor)

Significantly effective: The one that lost the power razor.

Effective: A weaker losing force.

Slightly effective: A slightly weaker force losing.

Invalid: No change in losing force.

(Evaluation of the improvement effect of losing force)

:: The proportion (percentage) of the test subjects showing remarkable, effective and somewhat effective was 80% or more.

〇: The proportion (effective rate) at which the subject shows a markedly effective, effective, or slightly effective (effective rate) is 50% or more to less than 80%.

Δ: The proportion (effective rate) at which the test subjects showed remarkable, effective, and somewhat effective was 30% or more and less than 50%.

(3) Skin irritation

In the above-described skin roughness improvement effect test and force razor loss improvement effect test, skin irritation was evaluated according to the following criteria.

：: 0% of subjects had a burning sensation on the skin.

〇: Less than 5% of subjects had a burning sensation on the skin.

△: The percentage of subjects with a burning sensation on the skin was less than 10%.

X: 10% or more of the subjects had a burning sensation on the skin. Table 5 Ingredient Sample control

2 3 4 5 6 Compound 1 0.5 0.2 — —

Compound 2 1 1 0,5 0.2 1 1

Compound 3-0.5 0.2

Crude fraction 0.5

Glycerin 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0

1,3—French, Ricoh / Le 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0

Etano 1 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0

Polyoxyethylene (20 mol)

Alcohol / alcohol 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 Roughness improvement effect ◎ 〇 ◎ 〇 ◎ ◎ ◎ 〇 Δ

(Kamiso!) Loss improvement effect ◎ 〇 ◎ 〇 ◎ ◎ ◎ Δ

Skin irritation ◎ ◎ ◎ ◎ ◎ ◎ ◎ 試料 As is clear from Table 5, the samples containing Compounds 1 to 3 or a crude fraction containing these as the active ingredients are more resistant to rough skin and loss of force than the control. And showed excellent improvement effect, and no skin irritation was observed.

Test example 3 Actual use test by replica method

Using the samples 1 to 7 of Test Example 2 and a control lotion, a skin roughness improvement effect test was performed by a replica method.

In other words, the skin surface morphology of a healthy female person (face) was replicated using the replica method and observed with a microscope (17 times). Panels whose skin roughness was judged to be 1 or 2 based on the criteria shown in Table 6 based on the state of the skin pattern and the peeling state of the stratum corneum (rough skin panel) Twenty people applied the lotions of samples 1 to 7 and the control twice a day for 2 weeks to the left and right half of the face. Two weeks later, the skin condition was observed again according to the replica method described above, and evaluated according to the criteria shown in Table 6. Table 7 shows the results. Table 6 Criteria for flat points

1 Skin sulcus, skin crevice disappeared, and widespread stratum corneum _c

2 Skin groove and skin hills are unclear and horny layer is turned up.

3 Skin sulcus and skin ridges are observed, but flat.

4 Skin groove and skin hills are clear.

5 Skin grooves and skin ridges are clear and well-organized.

Table 7 Replica evaluation samples Control

1 2 3 4 5 6 7

1 0 0 0 0 0 0 0 1

2 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, in the replica method, the lotion of the present invention was used as the control lotion. Compared with the case, it has a remarkable effect of improving rough skin.

Test Example 4 Tyrosinase activity inhibitory effect and melanin formation inhibitory effect

B16 melanoma seeded on a 96-well microplate was cultured in a culture solution (MEM + 10% FBS + theophylline) containing compound 1 or compound 2 at each concentration for 3 days. The culture solution was removed, 100 L of PBS (pH 7.4) containing 10 mM L-DOPA and 1% Triton-X was added, and the mixture was reacted at 37 ° C for 20 minutes. The ₄ 75 nm absorbance at the microphone port plate reader before and after the reaction was measured. From the change in absorbance before and after the reaction, the tyrosinase activity inhibition rate of each test compound in the cell line was calculated.

In addition, as a melanin production inhibitory effect, the plate was observed with a microscope through a polarizing filter, and evaluated in three stages (effective + 10, slightly effective 10, and no effect 1). Table 8 shows the results.

As can be seen from Table 8, compounds 1 and 2 exhibited an inhibitory effect on tyrosinase activity in cell lines even at concentrations as low as 0.005 mM and 0.001 mM. Also, it was excellent in melanin production inhibitory effect. Therefore, it is understood that these are very useful as whitening agents. Table 8 Compound Concentration (raM) Inhibition rate of P-Pinase "(%) Inhibitory effect on melanin production Compound 1 0.01 01 80 + +

0.005 55 + Compound 2 0.01 0.01 +

0.005 30 +

Example Example 1 Cream

(Prescription)

Stearic acid '5.0% by mass

Stearyl alcohol 4.0

Isopropyl myristate 8.0

Glycerin monostearate 3.0

Propylene glycol 10.0

Compound 1 0.1

Caustic potash 0.2

Sodium bisulfite 0.05

Preservative

Spice

Ion exchange water

(Formulation method)

Add propylene dalicol and caustic potash to the ion-exchanged water, dissolve and heat to 70 ° C (aqueous phase). Mix the other ingredients, heat and melt, and keep at 70 ° C (oil phase). Add the oil phase slowly to the water phase, and after adding all of them, keep the temperature for a while to allow the reaction to occur. Then, homogenize with a homomixer and cool to 30 ° C with good mixing. Example 2 Cream

(Prescription)

Stearate 5.0 mass ^_0/0

Sorbitan monostearate esternole 2.5

Polyoxyethylene (20 mol)

Sorbitan monostearate 1.5

Arbutin 7.0

Sodium bisulfite 0.03

Propylene glycolonele 10.0 Compound 2 05

Glycerin trioctanoate 100

Squalene 5 0

Otatyl paradimethylaminobenzoate 30

Disodium ethylenediaminetetraacetate 0 01

Echinoreno Raven 0 3

Appropriate amount of fragrance

Ion exchange water residue

(Formulation method)

The ion-exchanged water was dissolved by adding propylene glycol and ethylenediaminetetraacetic acid sodium salt, and kept at 70 ° C (aqueous phase). The other components are mixed and heated to dissolve and maintained at 70 ° C (oil phase). The oil phase is gradually added to the aqueous phase, pre-emulsified at 70 ° C, and uniformly emulsified by a homomixer. The mixture was cooled to 30 ° C with good stirring. Example 3 Cream

(Prescription)

50% by weight of solid paraffin

Beeswax 0 0

Vaseline 5 0

Liquid paraffin 4 0

Glycerin monostearate 2, 0

Polyoxyethylene (20 mol)

Sonorebitan monola diester phosphate

Soap powder 0

Borax 0, 2

Compound 1 05

Compound 2 0.05

Sodium bisulfite 0.03 Echinoreno Raven 0.3

Appropriate amount of fragrance

Ion exchange water

(Formulation method)

Add soap powder and borax to ion-exchanged water, dissolve by heating and maintain at 70 ° C (aqueous phase). Mix the other ingredients, heat and melt, and keep at 70 ° C (oil phase). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After the reaction is completed, emulsify the mixture uniformly with a homomixer. After emulsification, cool to 30 ° C while stirring well. Example 4 Emulsion

(Prescription)

Stearic acid 25 mass °

Cetinorea Noreco Nore 5

Vaseline 5 0

Liquid paraffin 0 0

Polyoxyethylene (10 mol)

Monooleate 2, 0

Polyethylene glycolone 1500 3, 0

Triethanolamine 0

Carboxybule polymer 0 05

Mouth—Mouth: ¾: Cabochonore 941, B.F.Goodrich Chemical company)

Compound 1 0.01

Sodium bisulfite 0.01

Ethilparaben 0.3

Spice

Ion exchange water

(Formulation method)

Dissolve the carboxybutyl polymer in a small amount of ion-exchanged water (phase A) Add polyethylene glycol 1500 and triethanolamine to the exchanged water, dissolve by heating, and maintain at 70 ° C (aqueous phase). Mix the other ingredients, heat and melt, and keep at 70 ° C (oil phase). Add oil phase to water phase, pre-emulsify, add phase A, homogenize homogeneously with homomixer, and after emulsification, cool to 30 ° C while stirring well. Example 5 Emulsion

(Prescription)

Microcrystalline wax 1.0 wt ^_0/0

Mitsuwa 2.0

Lanolin 20.0

Liquid paraffin 10.0

Squalane 5.0

Sonorebitan sesquioleate estenole 4.0

Polyoxyethylene (20 mol)

'Acid ester 1.0

Propylene Dali Cornole 7.0

Compound 21.0

Sodium bisulfite 0.01

Echinoreno Raven 0.3

Appropriate amount of fragrance

Ion exchange water residue

(Formulation method)

Add propylene glycol to ion-exchanged water and heat to maintain at 70 ° C (aqueous phase). Mix the other ingredients, heat and maintain at 70 ° C (oil phase). While stirring the oil phase, gradually add the water phase to the mixture and homogenize with a homomixer. After emulsification, cool to 30 ° C while stirring well. Example 6 Jelly (Prescription)

95% ethyl alcohol 0.0 mass%

Dipropylene dalicol 5.0

Polyoxyethylene (50 mol)

Taylor Reinore Noreco-Nore-Tenore 2.0

Forced ruboxy vinyl polymer 1.0

(Commercial fib name: Rikiichi Boponore 940, B.F.Goodrich Chemical company)

Caustic soda 0.1 5

L—Arginine 0.1

Compound 15.0

2-hydroxy-1 4-methoxy

Benzophenone sodium snolefonate 0.05

Ethylenediamine tetraacetate ·

3 Sodium '2 water 0.05

Methyl paraben 0.2

Spice

Ion exchange water residue

(Formulation method)

Carbopol 940 is uniformly dissolved in ion-exchanged water, while compound 1, polyoxyethylene (50 mol) oleyl alcohol ether is dissolved in 95% ethanol, and added to the aqueous phase. Next, after adding other ingredients, neutralize with caustic soda and L-anoreginin to thicken. Example 7 Serum

(Prescription)

(A phase)

Ethyl alcohol (95%) 0.0 mass%

Polyoxyethylene (20 mol) Octyldodecanol 0

Non-Tenino-Let-Chinolet

Compound 2 2 0

Mechinoreparaben 0 5

(Phase B)

Potassium hydroxide 0

(Phase C)

Glycerin 5.0

Dipropylene Darlicol 10.0

Sodium bisulfite 0.03

Carboxybule polymer 0.2

(Trade mouth—name: Carboponore 940, B.F.Goodrich Chemical company)

Purified water residue

(Formulation method)

Dissolve phase A and phase C uniformly, and add phase A to phase C for solubilization. Then, after adding phase B, filling is performed. Example 8 pack

(Prescription)

(A phase)

Dipropylene glycolone 5.0 mass%

Polyoxyethylene (60 mol)

Hardened castor oil 5.0

(Phase B)

Compound 3 0.05

Olive oil 5.0

Tocoprol acetate 0.2

Ethilparaben 0.2 Spice 0.2

(Phase C)

Sodium bisulfite 0 03

Polybutyl alcohol 3 0

(Degree of saponification 90, degree of polymerization 2,000)

Etano 1 7.0

purified water

(Formulation method)

Dissolve phase A, phase B and phase C uniformly, and add phase B to phase A for solubilization. In the next step, this is added to the C phase and then filled. Example 9 Solid foundation

(Prescription)

Talc 43.1 mass ^_0/0

Power Olin 15.0

Sericite 10.0

Zinc flower 7.0

Titanium dioxide 3.8

Yellow iron oxide 2. 9

Black iron oxide 0.2

Squalane 8.0

Isostearic acid 4.0

POE sorbitan monooleate 3.0

Isocetyl octoate 2.0

Compound 2 0.5

Preservative appropriate amount

Appropriate amount of fragrance

(Formulation method) The powdery components of talc and black iron oxide are sufficiently mixed in a blender, and the oily components of squalane and isocetyl octoate, compound 2, preservative, and fragrance are added, kneaded well, and the mixture is filled into a container and molded. Example 10 0 Emulsion type foundation (cream type)

(Prescription)

(Powder part)

0.3% by mass of titanium dioxide

Sericite 5.4

Power Olin 3.0

Yellow iron oxide 0.8

Bengala 0.3

Black iron oxide 0.2

(Oil phase)

Decamethylcyclopentasiloxane 5

Liquid paraffin 4 5

Polyoxyethylene modified

Dimethyl polysiloxane 4.0

Compound 1 0 5

(Aqueous phase)

Purified water 5 0 0

1, 3—Butylengenolecol 4 5

Sonorebitan sesquioleate estenole 3 0

Preservative

Spice

(Formulation method)

After heating and stirring the aqueous phase, the powder portion sufficiently mixed and pulverized is added to the mixture and treated with a homomixer. After adding the mixed oil phase under heating and homogenizing, add flavor while stirring. _C Example 11 cream to cool to room temperature Te

(Prescription)

Stearic acid 5.0% by mass

Stearyl alcohol 4.0

Isopropyl myristate 8.0

Glycerin monostearate 3.0

Cornole 10.0

Compound 2 0.0

Caustic potash 0.2

Sodium bisulfite 0.0

Preservative

Spice

Ion exchange water residue

(Formulation method)

Add propylene glycol and caustic potash to the ion-exchanged water, dissolve and heat to maintain at 70 ° C (aqueous phase). Mix the other ingredients, heat and melt, and keep at 70 ° C (oil phase). Add the oil phase slowly to the water phase, and after adding all of them, keep the temperature for a while to allow the reaction to occur. Then, homogenize with a homomixer and cool to 30 ° C with good mixing. Example 12 Cream

According to the following formulation, a cream was prepared in the same manner as in Example 2.

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

Screen 5.0

Sodium hyaluronate 1.0

Ethylenediaminetetraacetic acid trisodium salt 0.01

Gunolle course 0.5

Ascorbic acid darcoside 5.0

Ethilparaben 0.3

Appropriate amount of fragrance

Ion exchange water residue

(Formulation method)

To the ion-exchanged water was added and dissolved propylene daricol and ethylenediaminetetraacetic acid trisodium salt, and the mixture was kept at 70 ° C (aqueous phase). The other components are mixed and dissolved by heating and kept at 70 ° C (oil phase). The oil phase is gradually added to the aqueous phase, pre-emulsified at 70 ° C, and uniformly emulsified by a homomixer. The mixture was cooled to 30 ° C with good stirring. Example 13 cream

(Prescription)

5.0% by mass of solid paraffin

Beeswax 10.0

Vaseline 15.0

Liquid paraffin 41. 0

Glycerin monostearate 2.0

Polyoxyethylene (20 mol)

Sorbitan monolaurate esternole 2.0

Soap powder 0.1

Borax 0.2

Compound 11.0 Compound 21.0

Sodium bisulfite 0.03

Echinoreno Raven 0.3

Spice

Ion exchange water

(Formulation method)

Add soap powder and borax to ion-exchanged water, dissolve by heating and maintain at 70 ° C (aqueous phase). Mix with other ingredients, heat and melt, and maintain at 70 ° C (oil phase). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After the reaction is completed, emulsify the mixture uniformly with a homomixer. After emulsification, cool to 30 ° C while stirring well. Example 14 Emulsion

A: Oil phase

Squalane 5.0 mass%

Oleile rate 3.0

Vaseline 2.0

Sonorebitan sesquioleate estenole 0.8

Polyoxyethylene

Oleyl ether (20EO) 1.2

Compound 2 0.01

Evening primrose oil 0.5

Fragrance 0.3

Preservative qs

B: Water phase

1,3-butylene glycol4.5

Manoretit 4.0

Etano 1 3.0

Carboxyvinyl polymer 0.2 Potassium hydroxide 0.1

L-arginine L-aspartate 0.01

Serine 0.05

Purified water balance

(Formulation method)

An emulsion was obtained by a conventional method. Example 15 Emulsion

(Prescription)

Microcrystalline wax 1.0% by mass

Mitsuwa 2.0

Lanolin 20.0

Liquid paraffin 10.0

Squalane 5.0

Sorbitan sesquioleate 4.0

Polyoxyethylene (20 mol)

Sorbitan monooleate

Propylene glycolone 7

Compound 1 10

Sodium bisulfite 0

Ethilparaben 0

Spice

Ion exchange water

(Formulation method)

Add propylene glycol to ion-exchanged water and heat to maintain at 70 ° C (aqueous phase). Mix the other ingredients, heat and maintain at 70 ° C (oil phase). While stirring the oil phase, gradually add the water phase to the mixture and homogenize with a homomixer. After emulsification, cool to 30 ° C while stirring well. Example 16 Jelly

(Prescription)

9 5. /. Ethyl alcohol 0.0 mass%

Dipropylene Darikonole 5.0

Polyoxyethylene (50 mol)

Sairei Reinore T Record-No-Tenore 2.0

Carboxybule polymer 1.0

(Business name: Carbo Ponole 940, B.F.Goodrich Chemical company)

Caustic soda 0.1 5

L—Arginine 0.1

Compound 3 7.0

2-Hydroxy-1-4-Methoxybenzo

Sodium phenone sulfonate 0.05

Ethylenediamine tetraacetate ·

3 sodium27.05

Methyl paraben 0.2

Appropriate amount of fragrance

Ion exchange water residue

(Formulation method)

Dissolve Carbopol 940 uniformly in ion-exchanged water, then dissolve Compound 3, polyoxyethylene (50 mol) oleyl alcohol ether in 95% ethanol, and add to the aqueous phase. Next, after adding other components, neutralize with caustic soda and L-arginine to make it viscous. Example 17

(1) Compound 12.0 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) Hardened castor oil 5.0

(7) Squalane 2.0

(8) Liquid paraffin 3.0

(9) Fragrance 0.1

(10) Purified water residue

(Formulation method)

(1) to (5) and (10) were mixed, and heated and dissolved (6), (7), (8) and (9) were stirred and mixed to obtain a serum. Example 18 pack

(1) Polybutyl alcohol 00 mass%

(2) Polyethylene glycol (molecular weight 400) 0 4

(3) Glycerin 30

(4) Ethanol (95%) 80

(5) Compound 1 3 0

(6) Compound 2 3 0

(7) Preservatives 0.1

(8) Fragrance 0.1

(9) Purified water residue

(Formulation method)

At room temperature, (4), (5), (6), (7) and (8) were mixed and dissolved, and (1), (2), (3) and (9) were mixed and dissolved at 80 ° C. Then, the mixture was allowed to cool to room temperature to obtain a pack. Example 19 Solid foundation

(Prescription) Talc 43, mass%

Power Olin 15 0

Sericite 10 0

Zinc flower 7 0

Titanium dioxide 3 8

Yellow iron oxide 2 9

Black iron oxide 0 2

Squalane 8 0

Isostearic acid 4 0

Monooleic acid POE Sorbitan 3 0

Isosethyl octoate 20

Compound 3 0 5

Preservative

Spice

(Formulation method)

The powdery components of talc and black iron oxide are thoroughly mixed with a blender, and the oily components of squalane and isocetyl octoate, compound 3, preservative, and fragrance are added, kneaded well, and then filled into a container and molded. Example 20 Emulsion type foundation (cream type)

(Prescription)

(Powder part)

10.3% by mass of titanium dioxide

Sericite 5.4

Kaolin 3.0

Yellow iron oxide 0.8

Bengala 0.3

Black iron oxide 0.2 (Oil phase)

Decamethylcyclopentasiloxane 1.5

Liquid paraffin 4.5

Polyoxyethylene modified

Dimethylpolysiloxane 4.0

Compound 2 1.5

(Aqueous phase)

Purified water 50.0

1, 3—Butylengrenore 4.5

So ^ / bitansesquioleic acid esternole 3.0

Preservative appropriate amount

Appropriate amount of fragrance

(Formulation method)

After heating and stirring the aqueous phase, a powder portion sufficiently mixed and pulverized is added and subjected to a homomixer treatment. Further, the oil phase mixed by heating is added to the mixture, and the mixture is treated with a homomixer. Then, the mixture is cooled to room temperature by adding a flavor while stirring. Example 21 Cream

A: Oil phase

Stearate 10.0 mass ^_0/0

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 qs

B: Water phase

Glycerin 4.0

1, 2—pentanedionole 3.0

Hydroxium hydroxide 0.4

Magnesium phosphate ascorbate 0.1

Tranexamic acid 0.05

Trisodium edetate 0.05

Purified water residue

(Formulation method)

Heat the oil phase of A and the aqueous phase of B to 70 ° C respectively to completely dissolve. Add phase A to phase B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain a cream. Example 22 Emulsion

(Prescription)

2 stearate, 5 wt ^_0/0

Seti / Reanore Konore 1.5

Vaseline 5.0

Liquid paraffin 10.0

Polyoxyethylene (10 mol)

Monooleate 2.0

Polyethylene glycol 1500 3.0

Triethanolamine 1.0

Carboxybule polymer 0.05

(Product name: Carbopol 941, B.F.Goodrich Chemical company)

Coarse fraction 1.0

Sodium bisulfite 0.01

Ethilparaben 0.3 Spice

Ion exchange water residue

(Formulation method)

Dissolve carboxybutyl polymer in a small amount of ion-exchanged water (phase A). Add polyethylene dalicol 1500 and triethanolamine to the remaining ion-exchanged water, dissolve by heating, and maintain at 70 ° C (aqueous phase). Mix the other ingredients, heat and melt, and keep at 70 ° C (oil phase). Add oil phase to water phase, pre-emulsify, add phase A, homogenize uniformly with homomixer, cool to 30 ° C while stirring well after emulsification. Example 23 Serum

(Prescription)

(Phase)

Ethyl alcohol (95%) 0.0 mass%

Polyoxyethylene (20 mol)

Otachildodecanol 0

Non-Tenino Nolech / Rietenore 0,

Coarse fraction 2 0

Methyl paraben 0, 5

(Phase B)

Hydroxidation room 0,

(Phase C)

Glycerin 5 0

Dipropylene dalicol 0 0

Sodium bisulfite 0 03

Carboxybule polymer 0 2

, Trade name: Carhoponore 940, B.F.Goodrich Chemical company)

purified water

(Formulation method) Dissolve phase A and phase C uniformly, and add phase A to phase C for solubilization. Then, after adding phase B, filling is performed. Example 24 pack

(Prescription)

(A phase)

Dipropylene daric cone 5.0 mass%

Polyoxyethylene (60 mol)

Hardened castor oil 5.0

(Phase B)

Coarse fraction 5 0

Olive oil 5.0

Tocofe acetate 0.2

Ethilparaben 0.2

Spice 0.2

(Phase C)

Sodium bisulfite 0.03

Polybutyl alcohol 3.0

(Degree of saponification 90, degree of polymerization 2,000)

Ethanol 7.0

purified water

(Formulation method)

Dissolve phase A, phase B and phase C uniformly, and add phase B to phase A for solubilization. In the next step, this is added to the C phase and then filled. Example 25 Solid foundation

(Prescription)

Talc 43.% by mass Kaolin 1 5 0

Serisite 10 0

Zinc flower 7 0

Titanium dioxide 3 8

Yellow iron oxide 2 9

Black iron oxide 0 2

Squalane 8 0

Isostearic acid 4 0

Monooleic acid POE Sorbitan 3 0

Isosethyl octoate 20

Coarse fraction 0

Preservative

Spice

(Formulation method)

The powdery components of talc and black iron oxide are sufficiently mixed in a blender, and the oily components of squalane and isocetyl octoate, a crude fraction, a preservative, and a fragrance are added, kneaded well, and the mixture is filled into a container and molded. Example 26 Emulsion type foundation (cream type)

(Prescription)

(Powder part)

Titanium dioxide 10.3 mass ^_0/0

Sericite 5.4

Kaolin 3.0

Yellow iron oxide 0.8

Bengala 0.3

Unusual iron oxide 0.2

(Oil phase) Decamethinoresic mouth pentasiloxane 5

Liquid paraffin 4, 5

Polyoxyethylene modified

Dimethylpolysiloxane A, 0

Coarse fraction 2 0

(Aqueous phase)

Purified water 5 0 0

1, 3—Butylengrenore 4 4 5

Sorbitan sesquioleate 3 0

Preservative appropriate amount

Appropriate amount of fragrance

(Formulation method)

After heating and stirring the aqueous phase, a powder portion sufficiently mixed and pulverized is added and subjected to a homomixer treatment. Further, the oil phase mixed by heating is added, and the mixture is treated with a homomixer. Then, a flavor is added with stirring, and the mixture is cooled to room temperature. Example 2 7 Jelly

(Prescription)

9 5. /. Ethyl alcohol 0.0 mass%

Dipropylene Darikonole 5.0

Polyoxyethylene (50 mol)

Taylor Reynoreko-No-Re-Tenore 2.0

Carboxyvinyl polymer 1.0

(Product name: Cappopo 940, B.F.Goodrich Chemical company)

Caustic soda 0.1 5

L—Arginine 0.1

Crude fraction 7.0

2-hydroxy-1- 4-methoxybenzo Sodium phenone sulfonate 0.05

Ethylenediamine tetraacetate ·

3 Sodium '2 water 0.05

Methyl paraben 0.2

Spice

Ion exchange water

(Formulation method)

Carbopol 940 is uniformly dissolved in ion-exchanged water, while the crude fraction and polyoxyethylene (50 mol) oleyl alcohol ether are dissolved in 95% ethanol and 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 28 Serum

(Prescription)

(A phase)

Ethyl alcohol (95%) 0.0 mass%

Polyoxyethylene (20 mol)

Octyldodecanol 1.0

No.テテレ 1 0.1

Crude fraction 3.0

Methyl paraben 0.1 5

(Phase B)

Potassium hydroxide 0.1

(Phase C)

Glycerin 5.0

Dipropylene glycolone 0.0

Sodium bisulfite 0.03

Carboxybule polymer 0.2 (Product name: Carboponore 940, BFGoodrich Chemical company) Purified water residue

(Formulation method)

Dissolve phase A and phase C uniformly, and add phase A to phase C for solubilization. Then, after adding phase B, filling is performed. Example 29 pack

(Prescription)

(Phase)

Dipropylene daric cone 5.0 mass%

Polyoxyethylene (60 mol)

Hardened castor oil 5 0

Coarse fraction 5 0

(Phase B)

Olive oil 5 0

Tocofe acetate 0 2

Echinore / Kuraben 0 2

Fragrance 0 2

(Phase C)

Sodium bisulfite 0 03

Poly Binino Leano Reconore 3 0

(90 saponification, 2,000 polymerization)

Ethanol 7.0

purified water

(Formulation method)

Dissolve phase A, phase B and phase C uniformly, and add phase B to phase A for solubilization. In the next step, this is added to the C phase and then filled. Example 30 Lotion

(1) Compound 1005% by mass

(2) Aspartic acid 0

(3) Tocoffe acetate 0 01

(4) Glycerin 4 0

(5) 1,3-butylene glycolone 4 0

(6) Ethanore 8 0

(7) Polyoxyethylene (60)

Hardened castor oil 0 5

(8) Methyl paraben 0 2

(9) Cunic acid 0 05

(10) Sodium citrate 0

(11) Fragrance 0 05

(12) Purified water residue

(Formulation method)

(2), (4), (5), (9) and (10) were dissolved in (12) to give a purified aqueous solution. Separately, (1), (3), (7), (8), and (11) are dissolved in (6), and this is added to the above-mentioned purified aqueous solution to solubilize and filtered to obtain a lotion. Example 31, lotion

A: Alcohol phase

50% by weight of ethanol

P OE Oleino Leano Recall Ete Nore 2 0

2—Echinore

—P—Dimethylaminobenzoate 0 18

Compound 20

Fragrance 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

Hydroxypropyl β

Cyclodextrin 0

Ethylenediamine hydroxyethynole

Triacetic acid 3 Sodium 0

Lysine 0 05

Tranexamic acid 1.0

Purified water residue

(Formulation method)

It was added the alcohol phase Α to the water phase of the beta, _c Example 32 lotion was obtained lotion solubilized

A: Alcohol phase

Etano mono 5.0 mass%

P OE Oreil Arcono Le Etenore 2.0

2—Echinore

—P—Dimethylaminobenzoate 0 18

Fragrance 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

Trimethylglycine 3 0

Coarse fraction 0 Hydroxypropyl / 3

Cyclodextrin 1.0

Ethylenediamine hydroxyechinole

Sodium triacetate 1.0

Lysine 0.05

Tranexamic acid 1.0

Purified water residue

(Formulation method)

The alcohol phase of A was added to the aqueous phase of B and solubilized to obtain a lotion. Example 33 Emulsion foundation

A: Oil phase

Compound 10

Compound 20

Setano 1 3 5

Deodorized lanolin 4 0

Hohono oil 5, 0

Vaseline 2, 0

Squalane 6, 0

Stearic acid monoglycerin ester 2.5

POE (60) hydrogenated castor oil 1.5

POE (20) Cetyl ether 1.0

Pyridoxine reno ,. Noremitate 0.1

Preservative '' qs

Fragrance 0.3

B: Water phase

Propylene glycolone 0 0

Whey 0

Mouth | ¾ 2 0 Histidine 5.0

Purified water residue

(Preparation method) Heat the oil phase of A and the aqueous phase of B to 70 ° C, respectively, and completely dissolve them. Add phase A to phase B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain an emulsion foundation.

As described above, the compounds 1 to 3 of the present invention are excellent in PAF antagonistic activity, and when combined therewith, have excellent effects in improving and preventing various skin diseases, rough skin, etc. A small amount of external preparation for skin can be obtained. In addition, since it also has a tyrosinase activity'14 inhibitory action and a melanin production inhibitory action, it can also exhibit a whitening effect.

Claims

The scope of the claims

1. An external preparation for skin, comprising at least one of the following compounds 3 as an active ingredient.

2. The external preparation according to claim 1, further comprising an extract of the genus Zingiberaceae belonging to the genus Zingiberaceae containing at least one of the compounds 1 to 3 as an active ingredient.

3. The external preparation according to claim 1 or 2, wherein at least one of the compounds 1 to 3 or an extract of the genus Zingiberaceae belonging to the genus Zingiberaceae is an agent for improving skin roughness.

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, further comprising an extract of a plant belonging to the genus Zingiberaceae, which includes at least one of the compounds 1 to 3 as an active ingredient.

6. A tyrosinase activity inhibitor comprising at least one of compounds 1 and 2 as an active ingredient.

7. The tyrosinase activity inhibitor according to claim 6, further comprising an extract of the genus Zingiberaceae, which contains at least one of the compounds 1 to 2 as an active ingredient.

8. A whitening agent comprising the tyrosinase activity inhibitor according to claim 6 or 7 as an active ingredient.