JPH07277939A - Skin external preparation - Google Patents

Abstract

PURPOSE:To obtain a skin external preparation, capable of sufficiently exhibiting performances of each pharmacodynamic agent and extremely useful in beauty and medical use. CONSTITUTION:The characteristic of this skin external preparation comprises containing (A) an extract of Flor de Manita and (B) one or two or more pharmacodynamic agents selected from active oxygen removers, antioxidants, cell activators, anti-inflammatory agents, tyrosinase activity inhibitors and humectants.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin external preparation, and more particularly to a skin external preparation containing a flow demanita extract and a specific medicinal agent.

[0002]

2. Description of the Related Art Conventionally, cosmetics such as emulsions, creams, lotions, packs, dispersions, and detergents, and pharmaceuticals such as ointments, creams, and liquids for external use should be given a predetermined medicinal effect. The medicinal properties are added for the purpose. For example, in order to prevent skin darkening and inflammation caused by sunburn, stains caused by pigmentation, freckles, and the like, calamine and the like, ascorbic acid, glutathione,
Contains colloidal sulfur, hydroquinone, kojic acid, cinnamic aldehyde, etc.It also improves skin roughness, prevents skin aging, activates cells, treats cuts and wounds after shaving, cracks, cracks, sores, hemorrhoids, Medicinal ingredients such as allantoin, aloe extract, ginseng extract, shikon extract, placenta extract, bovine blood deproteinate, and fermented metabolite are blended for the purpose of treating wounds such as improvement of burns.

[0003]

However, in the external preparation for skin containing these medicinal components, the medicinal components are not sufficiently effective, or the desired medicinal properties are obtained by deteriorating in the preparation. In many cases, no improvement was desired.

[0004]

[Means for Solving the Problems] As a result of intensive studies to improve the effect of the medicinal component of the external preparation for skin, the present inventors have recently reported that it has been reported to have a whitening effect on the flow demanita extract. It was found that the action inherently possessed by the medicinal agent can be sufficiently exerted by combining and the medicinal agent and the present invention was completed.

That is, the present invention provides the following components (A) and (B) (A) flow demanita extract (B) active oxygen scavenger, antioxidant, cell activating agent, anti-inflammatory agent, tyrosinase activity inhibition A skin external preparation containing one or more medicinal agents selected from agents and humectants.

The flow demanita extract, which is the component (A) of the external preparation for skin of the present invention, is already known to have a whitening effect (Japanese Patent Laid-Open No. 5-170638). For example, it can be produced by the following method. You can

[0007] That is, one of the plants native to Mexico, Flor de Manita [aka MACPALX
Also referred to as OCHITL] by heat-extracting a dried product or a crushed product of the dried product with an extraction solvent, and then extracting the extract by filtering the extract to obtain an extract or, if necessary, further extracting the extract at 60 ° C or lower. A flow demanita extract can be obtained by concentrating under reduced pressure while heating at a temperature of 3 to dryness to obtain a dry extract.

As the extraction solvent, alcohol (methanol, ethanol, propanol, isopropyl alcohol or the like), water or the like can be used, or a mixed solution of these can be used. An example of a preferable extraction method is a method in which hydrous alcohol having an alcohol concentration of 20 to 70% is used and extraction is performed at a temperature of about 50 ° C. for about 1 hour, and an extract can be efficiently obtained.

The content of the flow demanita extract in the external preparation for skin of the present invention is preferably 0.1 as a dry solid content.
The amount is 0001 to 10% by weight (hereinafter simply referred to as "%"), and more preferably 0.01 to 5%. When the extract is used, the concentration of the extract is not limited as long as the content of the dry solid as a solute is within the above range. The content of this flow demanita extract is 0.
If it is less than 0001%, a sufficient effect may not be obtained, and if it exceeds 10%, the effect is not further increased.

On the other hand, the drug effect of the component (B) of the present invention is selected from active oxygen scavengers, antioxidants, cell activators, anti-inflammatory agents, tyrosinase activity inhibitors and moisturizers. The following are examples of typical medicinal agents.

(Active oxygen scavenger and antioxidant) Examples of the active oxygen scavenger include carotenoids such as SOD, mannitol and beta-carotene, hydroquinone,
Examples thereof include plant extracts containing flavonoids such as bilirubin, cholesterol, tryptophan, histidine, quercetin, quercitrin, catechin, catechin derivatives, gallic acid, gallic acid derivatives, and augon extract in its components.

As the antioxidant, vitamin A such as vitamin A acetate and vitamin A palmitate is used.
And derivatives thereof and salts thereof, vitamin Bs and derivatives thereof and salts thereof, vitamin C such as phosphate-L-ascorbyl magnesium, disodium L-ascorbate sulfate, vitamin C dipalmitate and derivatives thereof, and Salts thereof, vitamin Ds and derivatives thereof, salts thereof, vitamin E such as vitamin E acetate and derivatives thereof, salts thereof, glutathione and derivatives thereof and salts thereof, B
Examples include HT and BHA.

Of the above active oxygen scavengers and antioxidants,
Particularly preferred are SOD, beta-carotene, vitamin C and derivatives thereof and salts thereof, vitamin E and derivatives thereof and salts thereof.

(Cell activating agent) Examples of the cell activating agent include deoxyribonucleic acid and salts thereof, adenylic acid derivatives such as adenosine triphosphate and adenosine monophosphate and salts thereof, ribonucleic acid and salts thereof, and guanine. , Xanthine and their derivatives and their salts, and other nucleic acid-related substances; serum-derived protein extracts, spleen extracts, placenta extracts, chicken cob extracts, royal jelly and other animal-derived extracts; yeast extracts, lactic acid extract , Bifidobacteria extract,
Extracts derived from microorganisms such as ganoderma lucidum extract; extracts derived from plants such as carrot extract, assembly extract, rosemary extract, psyllium extract, garlic extract, hinokitiol, cepharanthin; α- or γ-linolein Examples thereof include acids, eicosapentaenoic acid and derivatives thereof, succinic acid and derivatives thereof and salts thereof, estradiol and derivatives thereof and salts thereof, and the like.

Of these cell activating agents, particularly preferable are deoxyribonucleic acid and salts thereof, adenosine triphosphate and salts thereof, serum deproteinization extract, placenta extract,
Examples include yeast extract, carrot extract, succinic acid and its derivatives, and salts thereof.

(Anti-inflammatory agent) As an anti-inflammatory agent,
Glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid,
Phenylbutazone, indomethacin, ibuprofen,
Ketoprofen, allantoin, guaiazulene and their derivatives and salts thereof, ε-aminocaproic acid, zinc oxide, diclofenac sodium, licorice extract, aloe extract, shikon extract, salvia extract,
Arnica extract, chamomile extract, birch extract, Hypericum extract, eucalyptus extract, mukuroji extract and the like can be mentioned.

Among these anti-inflammatory agents, particularly preferable ones are glycyrrhizic acid, glycyrrhetinic acid, guaiazulene and their derivatives and salts thereof, ε-aminocaproic acid, licorice extract, aloe extract, shikon extract and chamomile. It is an extract.

(Tyrosinase activity inhibitor) Examples of the tyrosinase activity inhibitor include cysteine and its derivatives (for example, N, N′-diacetylcystine dimethyl) and salts thereof, Sophoraceae extract, Toki extract, Ibukitoranoo extract, Clara Examples include extract, hawthorn extract, white lily extract, hop extract, Neubara extract, Yokuinin extract and the like.

Among the inhibitors of tyrosinase activity, Yokuinin extract is a coix lacryma-job of the family Gramineae.
i L.var.ma-yuen (ROMAN) STAPF) obtained by extracting from seeds etc. excluding the seed coat. In addition, extracts of Sohakuhi, Touki, Ibukitoranoo, Clara, hawthorn, hop, Neubara, and lily lily are not particularly limited in the use part of those plants, and extracted using leaves, branches, stems, flowers, fruits, roots, etc., respectively. However, above all, it is preferable to use rhizomes for Ibukitoranoo, roots for Clara, hawthorn, fruits for Neubara, flowers for hops, and bulbs for white lily.

The extraction method for obtaining the tyrosinase activity inhibitor from each of the above-mentioned plants is not particularly limited, but it can be extracted, for example, using various suitable solvents at room temperature or under heating. Examples of the extraction solvent include water; lower monohydric alcohols such as methyl alcohol and ethyl alcohol; liquid polyhydric alcohols such as propylene glycol and 1,3-butylene glycol; lower alkyl esters such as ethyl acetate; carbonization such as benzene and hexane. Hydrogen; one or more ethers such as ethyl ether may be used. Among these, water or a water-soluble solvent, particularly water, ethyl alcohol, glycerin, or 1,3-butylene glycol, is preferably used.

The plant-derived tyrosinase activity inhibitor obtained under the above-mentioned conditions may be used as it is as an extracted solution, but if necessary, it may be subjected to treatments such as concentration and filtration and used appropriately. You can

(Humectant) As the moisturizer, mucopolysaccharides and proteins which are constituents of the skin and have been conventionally blended in cosmetics can be used.

Among them, the mucopolysaccharides include, for example, hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and keratan sulfate and salts thereof, and hyaluronic acid, chondroitin sulfate and salts thereof are preferably used. be able to.

Examples of the protein include collagen, elastin, keratin, their derivatives and salts thereof, and collagen is particularly preferable. The origin of each of these components is not particularly limited, and may be animal-derived, microbial-derived, or synthetic. There are no particular restrictions on the extraction method and purification method for natural sources.

The amount of the above-mentioned component (b), the medicinal agent, to be added to the external preparation for skin of the present invention varies depending on the kind of the medicinal agent, but is preferably in the following range.

That is, the active oxygen scavenger and / or the antioxidant is generally contained in the skin external preparation in an amount of 0.0001 to 5
%, Preferably 0.001 to 3%. Amount of active oxygen remover and / or antioxidant is 0.0001%
If it is less than the above range, a sufficient effect may not be obtained, and even if it exceeds 5%, the effect may not be further increased, and the formulation may be adversely affected.

From the viewpoint of stability over time, the cell activating agent is preferably incorporated in the skin external preparation in an amount of 0.001 to 5%, and particularly preferably in the range of 0.01 to 3%, and the anti-inflammatory agent is used in the skin external preparation. In general, 0.0001% to 5%, preferably 0.01 to 3%
Is. These cell activating agents and anti-inflammatory agents can be used alone or in combination of two or more.

Furthermore, the content of the tyrosinase activity inhibitor in the external preparation for skin is 0.0001 to 0.005 as a dry solid content.
It is preferable to add 10%, particularly 0.001 to 5%. If it is less than 0.0001%, a sufficient whitening effect cannot be obtained, and if it exceeds 10%, the effect does not increase, and in some cases, a problem such as coloring of the product may occur, which is not preferable. In addition, these can be used individually or in combination of 2 or more types.

Furthermore, mucopolysaccharides and / or moisturizers
Alternatively, the amount of protein incorporated into the external preparation for skin of the present invention is generally 0.0001% to 5%, preferably 0.001 to 3%.
Is. If the content of these is less than 0.0001%, sufficient effect may not be obtained, and 5%
Even if it exceeds the above range, no further increase in the effect is observed.

The external preparation for skin of the present invention is prepared by blending the essential components (A) and (B) with various forms of bases known as ordinary external preparations for skin according to a conventional method. be able to.

The form of the external preparation for skin is not particularly limited, and examples thereof include cosmetics such as emulsions, creams, lotions, packs, dispersions and cleaning agents, and pharmaceuticals such as ointments, creams and external preparations. The base of the external preparation may be a base depending on the form of these external preparations, for example, purified water, lower alcohols, polyhydric alcohols, oils and fats, surfactants, ultraviolet absorbers, thickeners, etc. Agents, dyes, preservatives, fragrances and the like can be used.

[0032]

EXAMPLES Next, the present invention will be described in more detail with reference to Reference Examples and Examples, but the present invention is not limited thereto.

Reference Example 1 Production of Flodemanita extract: About 100 g of dried matter of Flodemanita, which is one of the plants native to Mexico, was ground with a mixer. Put this pulverized product and 1 liter of 50% ethyl alcohol in a flask and stir at 50 ° C.
Reflux extraction was performed for 1 hour. After extraction, this solution is suction filtered, and the obtained filtrate is heated at 50 ° C. using an evaporator.
And concentrated under reduced pressure. Then, the obtained concentrated liquid is dried under reduced pressure,
10 g of a flow demanita extract was obtained as a brown crystal.

Test Example 1 Superoxide removal activity measurement test: The flow demanita extract obtained in Reference Example 1 and the active oxygen scavenger shown in Table 1 were used alone or as a mixture to prepare a sample, which was diluted with water. The superoxide removing activity was measured by the following measuring method. That is, the substrate solution [3.0 mM xanthine (dissolved in 0.05 M sodium carbonate buffer)] was added to 2.4 ml of 0.05 M sodium carbonate buffer (pH 10.2).
1 ml, 3.0 mM EDTA 0.1 ml, 0.15% (W
/ V) 0.1 ml of bovine serum albumin, 0.1 ml of 0.75 mM nitroblu-tetrazolium and 0.1 ml of each test sample.
1 ml was mixed and left at 25 ° C. for 10 minutes. Next, 0.1 ml of an enzyme solution [xanthine oxidase solution (diluted with purified water about 0.04 units / ml)] was added to start the reaction, and after incubation at 25 ° C for 20 minutes, 6 m
The reaction is stopped by adding 0.1 ml of M CaCl ₂ . Then, the absorbance (A) at 560 nm is measured.

The absorbance (B) of the sample to which purified water was added instead of the test sample was used as a control, and 6 was used as the blank of each sample.
After stopping the reaction by adding 0.1 ml of mM CaCl _2, the absorbance (C) of the sample to which 0.1 ml of xanthine oxidase was added was measured, and the superoxide removal rate was calculated from the following formula. The results are shown in Table 1.

[0036] A: Absorbance of sample by enzyme reaction B: Absorbance of control enzyme reaction C: Absorbance of sample without enzyme reaction

[0037]

[Table 1]

As is clear from the results in Table 1, the flow demanita extract alone had an SOD-like action,
It was shown that the combined use with SOD and Scutellaria extract exerts a synergistic effect and is extremely effective in removing active oxygen.

This means that the external preparation for skin of the present invention in which a flow demanita extract and an active oxygen scavenger are used in combination produces lipid peroxide, inflammation, and blackening due to active oxygen production in the skin by ultraviolet rays. , Has an extremely high preventive effect on aging.

Example 1 Emulsion: An emulsion was prepared according to the composition shown in Table 2 and the following production method, and its skin beautifying effect and skin aging preventing effect were examined. The results are shown in Table 3.

(Composition) Table 2 ─────────────────────────────────── Comparative product of the present invention Component (%) ───── ───────────── 1 1 2 3 ──────────────────────── ──────────── (1) Squalane 5.0 5.0 5.0 5.0 5.0 (2) Vaseline 2.0 2.0 2.0 2.0 (3) Beeswax 0.0. 5 0.5 0.5 0.5 (4) sorbitan sesqui 0.8 0.8 0.8 0.8 oleate (5) polyoxyethylene 1.2 1.2 1.2 1.2 1.2 oleyl ether (20E.O.) (6) 1,3-Butylene 5.0 5.0 5.0 5.0 5.0 Glycol (7) Flow demanita extract ^* 0.1 0.1- (8) dl-α -Tocopherol ^** 0.01-0.01- (9) Ethyl alcohol 5.0 5.0 5.0 5.0 (10) Preservative 0.20 .2 0.2 0.2 (11) Fragrance 0.1 0.1 0.1 0.1 0.1 (12) Xanthan gum 20.0 20.0 20.0 20.0 (2% aqueous solution) (13) Residual water production Residual volume Residual volume Residual volume ─────────────────────────────────── * In Reference Example 1 Manufactured ** Made by Wako Pure Chemical Industries

(Production Method) A. Components (6), (7), (9) and (13) are heated and mixed at 70 ° C.
Keep on. B. Components (1) to (5), (8) and (10) are heated and mixed, and the mixture is heated to 70 ° C.
Keep on. C. The above B was added to the above A and mixed, the component (12) was added to uniformly emulsify, the mixture was cooled to 30 ° C., the component (11) was added,
Mix uniformly to obtain an emulsion.

(Test method) Females aged 28 to 58 1
A panel of 5 people was applied to the face with an appropriate amount of the test emulsion after washing the face twice a day, morning and night, for 12 weeks. The beautiful skin and anti-aging effect of the application were evaluated according to the following criteria.

Skin beautifying effect: [Evaluation] [Content] Effectiveness The dullness of the skin became inconspicuous. Somewhat effective The dullness of the skin became less noticeable. Ineffective No change from before use.

Skin Aging Preventive Effect: [Evaluation] [Content] Effectiveness The scalp and gloss of the skin were improved. Slightly effective Skin tone and gloss were slightly improved. Ineffective No change from before use.

(Result) Table 3 ─────────────────────────────────── Beautiful skin effect Skin aging prevention Efficacy Test emulsion ──────────── ───────────── Effective Fair Effective Ineffective Effective Fair Effective Ineffective ────────── ──────────────────────── Product of the present invention 1 13 2 0 12 3 0 ──────────────── ────────────────── Comparative products 1 1 8 6 2 7 6 2 2 5 5 8 1 1 3 11 3 3 0 3 12 0 2 2 13 ──────── ────────────────────────── As is clear from the results shown in Table 3, the product of the present invention has a remarkable effect on the beautiful skin and the effect of preventing skin aging. It was

Example 2 Cream: A cream was prepared according to the composition shown in Table 4 and the following production method, and its skin beautifying effect and skin aging preventing effect were examined. The results are shown in Table 5.

(Composition) Table 4 ───────────────────────────────────── Component (%) ────── ─────────────── 2 3 4 5 6 7 ───────────────── ─────────────────── (1) Beeswax 6.0 6.0 6.0 6.0 6.0 6.0 6.0 (2) Cetanol 5.0 5. 0 5.0 5.0 5.0 5.0 (3) Reduced lanolin 5.0 5.0 5.0 5.0 5.0 5.0 5.0 (4) Squalane 30.0 30.0 30.0 30 .0 30.0 30.0 (5) Glycerin 4.0 4.0 4.0 4.0 4.0 4.0 4.0 Monostearate (6) Lipophilic monostea 2.0 2.0 2.0 2 .0 2.0 2.0 Glycerine phosphate (7) Polyoxyethylene sorbitan monora 2.0 2.0 2.0 2.0 2.0 2.0 Ethyl urate Ether (20 EO) (8) Flow hoax Nita 0.01 0.01 0.01 - - - extract ^* (9) ascorbic acid phosphoric acid ester 1.0 - - 1.0 - - Magnesium ^** (10) Beta − 0.01 − − 0.01 − Carotene ^*** (11) Preservative 0.2 0.2 0.2 0.2 0.2 0.2 (12) Fragrance 0.05 0.05 0.05 0.05 0.05 0.05 (13) Purified water Residual amount Residual amount Residual amount Residual amount Residual amount ───────────────────── ──────────────── * Manufactured in Reference Example 1 ** Made by Nikko Chemicals *** Made by Wako Pure Chemical Industries

(Production Method) A. Components (1) to (7), (11) and (12) are mixed and heated to 7
Keep at 0 ° C. B. Mix components (8) and (13) and heat to 70 ° C. C. B was added to A, mixed, cooled, (9) and (10) were added, and the mixture was mixed uniformly to obtain a cream. (Test method) Same as Example 1 (evaluation standard) 〃

(Results) Table 5 ───────────────────────────────────── Beautiful skin Effectiveness Skin Anti-aging effect Test cream ──────────── ──────────── Effective slightly effective Not effective Effective slightly effective Not effective ───────── ─────────────────────────── Inventive product 2 10 5 0 10 3 2 3 3 13 2 0 12 30 0 ─────── ──────────────────────────── Comparative product 4 2 5 8 7 1 7 5 5 5 4 6 4 4 6 5 6 6 3 7 5 3 7 3 7 0 4 11 0 2 13 ──────────────────────────────────── From the results in Table 5 As is apparent, the creams of the products 2 and 3 of the present invention mourn the "shiny" and "harri" of the skin. , Prevention of aging of the skin such as "dull", was effective in the improvement.

Example 3 Cosmetic water: (treatment) (%) (1) glycerin 5.0 (2) 1,3-butylene glycol 6.5 (3) polyoxyethylene sorbitan 1.2 monolaurate (20E.O.) (4) Ethyl alcohol 8.0 (5) Flow demanita extract ^* 1.0 (6) SOD ^** 0.5 (7) Preservative proper amount (8) Fragrance proper amount (9) Residual amount of purified water * The water produced in Reference Example 1. ** Sigma; obtained from human red blood cells (5.230 units /
mg)

(Production Method) A. Components (3), (4), (7) and (8) are mixed and dissolved. B. Components (1), (2), (5), (6) and (9) are mixed and dissolved. C. A and B were mixed and homogenized to obtain a lotion.

Example 4 Pack: (Method) (%) (1) Polyvinyl alcohol 20.0 (2) Ethyl alcohol 20.0 (3) Glycerin 5.0 (4) Kaolin 6.0 (5) ) Floedemanita extract ^* 0.05 (6) Scutellaria extract ^** 0.2 (7) Preservative 0.2 (8) Fragrance 0.1 (9) Residue of purified water * Reference example 1 Manufactured in ** Made by Ichimaru Falcos

(Production Method) A. Components (1), (3) to (5) and (9) are mixed, heated to 70 ° C. and stirred. B. Mix components (2), (7) and (8). C. Add the above B to the above A, mix and cool (6)
Were uniformly dispersed to obtain a pack.

Example 5 Washing agent: (treatment) (%) (1) Stearic acid 10.0 (2) Palmitic acid 8.0 (3) Myristic acid 12.0 (4) Lauric acid 4.0 (5) Oleyl alcohol 1.5 (6) Purified lanolin 1.0 (7) Fragrance 0.1 (8) Preservative 0.2 (9) Glycerin 18.0 (10) Potassium hydroxide 6.0 ( 11) Flodemanita extract ^* 0.5 (12) Acetic acid-dl-α-0.05 tocopherol ^** (13) Residual amount of purified water * Manufactured in Reference Example 1 ** Manufactured by Sigma

(Production Method) A. Components (9), (10) and (13) are mixed and heated to 70 ° C. B. Components (1)-(6), (8) and (12) are mixed and heated to 70 ° C. C. The above B was added to the above A, kept at 70 ° C for a while, cooled to 50 ° C after the saponification reaction was completed, and the components (7) and (1
1) was added and cooled to obtain a cleaning agent.

Example 6 Gel Ointment: (Method) (%) (1) Carboxyvinyl Polymer 1.0 (2) Triethanolamine 1.0 (3) 1,3-Butylene Glycol 10.0 ( 4) Floudemanita extract ^* 0.01 (5) Ergocalciferol ^** 0.02 (6) Residual amount of purified water * Manufactured in Reference Example 1 ** Manufactured by Sigma

(Production Method) A. Components (1) and (3) to (6) are mixed and dissolved. Ingredient (2) was added to B.A and mixed to homogenize to obtain a gel ointment.

Test Example 2 Wound healing test: Male Wistar rats aged 8 weeks were used as an experiment in groups of 10 rats. After shaving the back of the rat, under anesthesia, two back skins on the left and right were incised over 4 cm so as to be symmetrical with respect to the midline, and one was used as a drug application site and the other was used as a control site. Immediately after the incision, both incised sites were sutured and wiped with ethanol for disinfection. Among the sutured portions, any one of the present invention products 4 to 6 and comparative products 8 to 11 (dissolved in physiological saline) shown in Table 6 was applied to the drug application site, and physiological saline was applied to the control site. 0.1 ml was applied twice a day for 1 week. One week later, the dorsal skin was peeled off to make a strip-shaped section centering on the incision, and the tension strength of the skin section was measured with a rheometer.
It measured using NRM-2002J (made by Fudo Kogyo Co., Ltd.). The wound healing rate was calculated from the obtained measured value by the following formula. The results are shown in Table 6.

[0060]

[0061]

* 1 Manufactured in Reference Example 1. * 2 Wako Pure Chemical Industries * 3 Sansho Pharmaceutical * 4 Nikko Chemicals

As is clear from Table 6, when the flow demanita extract was combined with ATP, placenta extract or yeast extract, the wound healing rate was clearly higher than that when used alone. A synergistic effect of promoting wound healing was observed.

Example 7 Cream: A cream was prepared according to the composition shown in Table 7 and the following production method, and its skin beautifying effect and skin aging preventing effect were examined. The results are shown in Table 8.

(Composition) * 1 Manufactured in Reference Example 1 * 2 Sansho Pharmaceutical * 3 Pentafarm

(Production Method) A. Components (1) to (7), (11) and (12) are mixed and heated to 7
Keep at 0 ° C. B. Components (8) to (10) and (13) are mixed and heated to 70
Keep at ℃. C. B was added to A and mixed, and cooled to 30 ° C. to obtain a cream.

(Test Method) Female 4 to 26-52 years old
A panel of 5 people was applied to the face with an appropriate amount of each 2 test cream products after washing the face twice daily in the morning and at night for 12 weeks. The effect of applying beautiful skin and the effect of preventing skin aging were evaluated according to the same criteria as in Example 1. The results are shown in Table 8.

[0068]

As is clear from the above results, the creams of products 7 and 8 of the present invention in which the flow demanita extract and the placenta extract or bovine blood deproteinization were blended were compared with the creams in which these were blended alone. Prevents the loss of skin "shine" and "swelling", and skin aging phenomena such as "dullness".
The effect was excellent for improvement.

Example 8 Modified cosmetic water: (Method) Compounding amount (%) (1) Polyoxyethylene (60 EO) hydrogenated castor oil 1.0 (2) Ethanol 15.0 (3) Preservative 0.1 (4) Hinokitiol 0.01 (5) Perfume proper amount (6) Flow demanita extract ^{* 1} 2.0 (7) Citric acid 0.1 (8) Sodium citrate 0.3 (9) 1 , 3-Butylene glycol 4.0 (10) Residual amount of purified water * 1 Produced in Reference Example 1.

(Production Method) A. Components (1) to (5) are heated and mixed to dissolve. B. Components (6) to (10) are heated and mixed to dissolve. C. A and B were mixed to obtain a lotion.

Example 9 Emulsion: (Method) Blending amount (%) (1) Polyoxyethylene (10 EO) 1.0 Sorbitan monostearate (2) Polyoxyethylene (60 EO) 0.5 Sorbit tetraoleate (3) Glyceryl monostearate 1.0 (4) Stearic acid 0.5 (5) Behenyl alcohol 0.5 (6) Squalane 8.0 (7) Eicosapentaenoic acid 5.0 (8) ) Antiseptic 0.1 (9) Flow demanita extract ^{* 1} 0.1 (10) Carboxyvinyl polymer 0.1 (11) Sodium hydroxide 0.05 (12) Ethyl alcohol 5.0 (13) Refined Residual amount of water production (14) Suitable amount of fragrance * 1 Produced in Reference Example 1.

(Production Method) A. Components (9) to (13) are mixed by heating and kept at 70 ° C. B. Components (1) to (8) are mixed by heating and kept at 70 ° C. C. Add A to B, mix and emulsify uniformly. After cooling D.C., (14) was added and uniformly mixed to obtain an emulsion.

Example 10 Ointment: (Method) Compounding amount (%) (1) Stearic acid 18.0 (2) Cetanol 4.0 (3) Triethanolamine 2.0 (4) Glycerin 5.0 (5) Flow demanita extract ^{* 1} 1.0 (6) Succinic acid ^{* 2} 1.0 (7) Residual amount of purified water * 1 Manufactured in Reference Example 1 * 2 Wako Pure Chemical Industries

(Production Method) A. A part of the components (3), (4) and (7) is mixed by heating and the mixture is heated to 75 ° C.
Keep on. B. Heat mix components (1) and (2) and keep at 75 ° C. C. Add A slowly to B. While cooling DC, (5) and (6) dissolved in the rest of (7) were added to obtain an ointment.

Test Example 3 Anti-inflammatory effect and whitening effect: A lotion containing the drugs shown in Table 9 and 15% (v / v) of ethanol and the remainder being purified water was prepared and applied to the back of colored guinea pigs. The effect of sunburn on inflammation and pigmentation was examined. The results are shown in Table 10.

(Test method) Colored guinea pigs (10 in each group)
The back of each animal was shaved and irradiated with ultraviolet rays under anesthesia. UV irradiation is performed with Toshiba Corporation FL20S / BLB lamp and F
Three L20S / E30 lamps were simultaneously irradiated, and the amount of ultraviolet rays was 4.8 × 10 ⁴ erg / cm ² . 0.2 ml of the sample was rubbed well into the four places on the back of the guinea pig 24 hours before, immediately after the irradiation, and 12 hours after the irradiation, and 24 hours after the irradiation. The application site was thoroughly washed with warm water before irradiation with ultraviolet rays. The degree of inflammation was observed 24 hours after irradiation and the degree of pigmentation 7 days later.

[0078] * 1 Manufactured in Reference Example 1. * 2 Maruzen Pharmaceutical Co., Ltd. * 3 Wako Pure Chemical Industries Ltd. * 4 80% (v / v) ethanol 80 per 20 parts by weight of Sikon
Parts by weight were added, and the mixture was extracted at 40 to 50 ° C for 5 hours, filtered, and the filtrate was dried under reduced pressure.

(Evaluation Criteria) Evaluation Criteria for Inflammation (Anti-inflammatory Effect) 0: No inflammation is observed at all 1: Very little inflammation is observed 2: Inflammation is observed but the boundary with the non-irradiated site is unclear 3 : Inflammation was observed and the boundary with the non-irradiated area was clear

Evaluation criteria for pigmentation (whitening effect) 0: No pigmentation is observed at all 1: Very slight pigmentation is observed 2: Pigmentation is observed, but the boundary with the non-irradiated site is unclear 3: Pigmentation is observed and the boundary with the non-irradiated area is clear

According to the above evaluation criteria, each score is 1
Count how many out of 10 guinea pigs are below the score,
It judged according to the following judgment criteria.

(Criteria for Judgment) [Judgment] [Contents] Remarkable effect Among 10 animals, the number of guinea pigs with a score of 1 point or less is 8 or more. Effectiveness Out of 10 animals, the number of guinea pigs with a score of 1 or less is 6 or more. Somewhat effective out of 10 guinea pigs with a score of 1 or less are 4 or more. Ineffective 10 out of 10 guinea pigs with a score of 1 or less are 3 or less.

[0083]

From the results shown in Table 10, the lotion of the present invention containing the flow demanita extract and dipotassium glycyrrhizinate, guaiazulene or shikon extract has an anti-inflammatory effect and a whitening effect as compared with a lotion containing them alone. Is clearly superior.

Example 11 Cream: A cream was prepared by the following formulation and the following production method. (Method) Compounding amount (%) (1) Polyoxyethylene monostearate (40E.O.) 2.0 (2) Glyceryl monostearate (self-emulsifying type) 5.0 (3) Stearic acid 5.0 (4) Behenyl alcohol 0.5 (5) Squalane 15.0 (6) Cetyl isooctanoate 5.0 (7) Butylparaben 0.1 (8) Methylparaben 0.1 (9) 1,3-Butylene glycol 5.0 (10) Dipotassium glycyrrhizinate ^{* 1} 0.2 (11) Flodemanita extract ^{* 2} 0.5 (12) Purified water residual amount (13) Fragrance appropriate amount * 1 Maruzen Pharmaceuticals * 2 Reference Example 1 Manufactured in

(Production Method) A. Components (1) to (7) are heated and dissolved at 70 ° C. B. Components (8) to (12) are heated and dissolved at 70 ° C. C. Add A to B and emulsify. Ingredient (13) is added to DC and cooled to obtain a cream.

Example 12 Emulsion: An emulsion was prepared by the following formulation and the following production method. (Method) Compounding amount (%) (1) Polyoxyethylene sorbitan 1.0 Monostearate (10 EO) (2) Polyoxyethylene sorbit 0.5 Tetraoleate (60 EO) (3) Glyceryl monostearate 1.0 (4) Stearic acid 0.5 (5) Behenyl alcohol 0.5 (6) Refined avocado oil 4.0 (7) Glyceryl tri-2-ethylhexanoate 4.0 (8) Butylparaben 0.1 (9) ) Flodemanita extract ^{* 1} 1.0 (10) Guiaazulene 0.2 (11) Methylparaben 0.1 (12) Carboxyvinyl polymer 0.07 (13) 1,3-Butylene glycol 5.0 (14) Purified Residual amount of water produced (15) Sodium hydroxide 0.025 (16) Purified water 7.5 (17) Perfume Appropriate amount * 1 Produced in Reference Example 1.

(Production Method) A. Components (1) to (10) are heated and dissolved at 70 ° C. B. Components (11) to (14) are heated and dissolved at 70 ° C. C. Add A to B and emulsify. (15) to (17) are added to DC and cooled to obtain an emulsion.

Example 13 Chemical lotion: A lotion was prepared by the following formulation and the following production method. (Method) Compounding amount (%) (1) Polyoxyethylene hydrogenated castor oil (60E.O) 1.0 (2) Perfume proper amount (3) Ethanol 10.0 (4) Methylparaben 0.1 (5) ε -Aminocaproic acid 0.3 (6) Citric acid 0.1 (7) Sodium citrate 0.3 (8) 1,3-Butylene glycol 5.0 (9) Flow demanita extract ^{* 1} 0.01 (10) ) Residual amount of purified water * 1 Produced in Reference Example 1.

(Production Method) A. Components (1) to (5) are heated and dissolved at 70 ° C. B. Components (6) to (11) are heated and dissolved at 70 ° C. C. Add B to A and stir to obtain lotion.

Reference Example 2 Production of plant extract: Sohakuhi (Japanese bureau), Kujin (Clara) (Japanese bureau), Touki (Japanese bureau), Hop (flower spike) 1 each
70% (v / v) 100% ethyl alcohol per 0 g
ml was added, and the mixture was extracted at room temperature for 3 days with occasional stirring and filtered to obtain each plant extract.

Test Example 4 Tyrosinase activity inhibition test: Reference Example 1 according to the following method
With respect to the 0.5% (W / V) aqueous solution of the extract obtained in 1. and the extract obtained in Reference Example 2, the tyrosinase activity inhibition rate of the sample alone or in combination thereof was examined. That is, an enzyme solution [manufactured by Sigma, 28,000 units of tyrosinase 10 mg was added to each sample in 0.1 M phosphate buffer (pH 6.8)]
Dissolved in 20 ml] 0.1 ml was added, and 0.1 ml was added.
Add 1M phosphate buffer (pH 6.8) to make 4.0 ml,
This was incubated at 25 ° C for 10 minutes.

Next, a substrate solution [L-DOPA (Tokyo Kasei) 198.0, which was previously kept at 25 ° C., was added thereto.
mg dissolved in 100 ml of 0.1 M phosphate buffer (pH 6.8)] 1.0 ml was added and reacted for 10 minutes. After the reaction, the absorbance (OD _s ) at 475 nm was measured. Similarly, the absorbance (OD _HE ) at the time of reacting with the enzyme inactivated by heating and the absorbance (OD _B ) when the sample was not added were measured, and the activity inhibition rate of tyrosinase activity was calculated from the following equation. did.

[0094] OD _S : Absorbance of sample OD _B : Absorbance without addition of sample OD _HE : Absorbance when enzyme is inactive Table 11 shows the results.

[0095]

[Table 11]

As is clear from Table 11, when the flow demanita extract and the tyrosinase activity inhibitor were combined, the tyrosinase activity inhibitory effect was higher than when the flow demanita extract or the tyrosinase activity inhibitor was used alone. It showed a high and synergistic whitening effect.

Example 14 An emulsion having the composition shown in Table 12 was produced and evaluated for its whitening effect. The results are shown in Table 13.

[0098]

[Table 12]

<Production Method> A. (6) to (10), (14) and (15) are mixed by heating and kept at 70 ° C. B. (1) to (5), (11) and (12) were mixed by heating and kept at 70 ° C. C. B is added to A and mixed, and (13) is further added to uniformly emulsify and cool to 30 ° C. to obtain an emulsion.

<Whitening effect test> Females 25 to 51 years old 4
Using 5 people as a panel, twice daily in the morning and at night, and after washing the face, apply the emulsions of samples 10 to 15 to each face for 12 weeks, and perform the usage test. It was evaluated by. Evaluation criteria; Effective: Spots and freckles are not noticeable. Slightly effective: Spots and freckles have become less noticeable. Ineffective: No change.

[0101]

As is apparent from Table 13, the emulsions of the present invention (Samples 14 to 15) in which the flow demanita extract and the tyrosinase activity inhibitor were combined in combination were compared with Sample 10 containing none of them. Of course, as compared with Samples 11 to 13 in which the flow demanita extract or the tyrosinase activity inhibitor alone was blended, the effect of making spots and freckles inconspicuous was excellent, and a remarkable whitening effect was exhibited.

Example 15 Cosmetic water: <Method>% (1) Glycerin 5.0 (2) 1,3-Butylene glycol 6.5 (3) Polyoxyethylene sorbitan 1.2 Monolauric acid ester (20E) .O.) (4) Ethyl alcohol 8.0 (5) Flodemanita extract ^* 0.01 (6) Yokuinin extract ^** (as dry solids) 0.05 (7) Preservative proper amount (8) Fragrance Suitable amount (9) Residual amount of purified water ─────────────────────────────── Total 100.0 * Reference example 1 Made in. ** Made by Maruzen Pharmaceutical Co., Ltd.

<Production Method> A. (3), (4), (7) and (8) are mixed and dissolved. B. Mix and dissolve (1), (2), (5), (6) and (9). C. A and B were mixed and homogenized to obtain a lotion.

Example 16 Cream: <Method>% (1) Beeswax 6.0 (2) Cetanol 5.0 (3) Reduced Lanolin 5.0 (4) Squalane 30.0 (5) Glycerin Monostearate 4.0 (6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene sorbitan 2.0 Monolauric acid ester (20E.O.) (8) Flow demanita extract ^* 1.0 (9) Sawakuhi Extract ^** (as dry solids) 0.2 (10) Preservative 0.3 (11) Flavor 0.05 (12) Purified water Residual amount ─────────────── ───────────────── Total 100.0 * Manufactured in Reference Example 1 ** Maruzen Pharmaceutical Co., Ltd.

<Production Method> A. (1) to (7), (10) and (11) are mixed and heated to 70 ° C.
Keep on. B. Mix (8), (9) and (12) and heat to 70 ° C. C. B was added to A, mixed and cooled to obtain a cream.

Example 17 Washing agent: <Processing>% (1) Stearic acid 10.0 (2) Palmitic acid 8.0 (3) Myristic acid 12.0 (4) Lauric acid 4.0 (5) ) Oleyl alcohol 1.5 (6) Purified lanolin 1.0 (7) Perfume 0.1 (8) Preservative 0.2 (9) Glycerin 18.0 (10) Potassium hydroxide 6.0 (11) Flow Demanita extract ^* 0.2 (12) Hop extract ^** 0.01 (13) Purified water Residual amount ───────────────────────── ────── Total 100.0

* Manufactured in Reference Example 1. ** Made by Koei Kogyo Co., Ltd.

<Production Method> A. (9), (10) and (13) are mixed and heated to 70 ° C. B. Mix (1)-(6) and (8) and heat to 70 ° C. C. B was added to A, kept at 70 ° C. for a while, cooled to 50 ° C. after the saponification reaction was completed, (7), (11) and (12) were added and cooled to obtain a cleaning agent. .

Example 18 Emulsion: An emulsion was prepared by the composition shown in Table 14 and the following production method, and its rough skin improving effect was examined. The results are shown in Table 15.
Shown in.

[0111] * Manufactured in Reference Example 1. ** Made by Nikko Chemicals Co., Ltd. *** Made by Koken Co., Ltd.

(Production Method) A. The components (6), (8) to (10) and (14) were heated and mixed, and
Keep at 0 ° C. B. The components (1) to (5), (7), (11) and (12) were mixed by heating and kept at 70 ° C. C. The above B was added to the above A and mixed, and the component (13) was added to uniformly emulsify, and the mixture was cooled to 30 ° C. to obtain an emulsion.

(Test method) Female 3 to 23 years old 3
A panel of 0 persons was used to observe the skin condition on the day before skiing with a microscope camera, and the score was calculated according to the following criteria. The skin condition score was also obtained one day after returning from skiing. After that, the test milky lotion was applied after washing the face twice in the morning and at night every day for 7 days. Then, after 3, 5 and 7 days of skiing, the skin condition score was obtained in the same manner as above.

Skin condition score: [Score] [Status] 1 Skin crevices on the skin are not clear, and exfoliation of the keratin is observed. 2 The skin groove on the skin is slightly blurred or unidirectional. 3 Skin groove is recognized, but shallow or unidirectional. 4 Skin crevices are observed or are slightly mesh-like. 5 Skin groove is clearly visible or has a clean mesh.

[0115]

As is clear from the results of Table 15, the product 12 of the present invention in which the flow demanita extract and hyaluronic acid were combined.
And the product 13 of the present invention in which the flow demanita extract and collagen were combined were comparative products 20 to 2 each formulated alone.
Compared with No. 2 and the comparative product 23 not containing them, a remarkable effect of improving rough skin was shown.

Example 19 Cream: A cream was prepared according to the composition shown in Table 16 and the following production method, and its skin beautifying effect was examined. The results are shown in Table 17.
Shown in.

[0118] * Manufactured in Reference Example 1 ** Made by Seikagaku Corporation *** Made by Ichimaru Falcos

(Production Method) A. Components (1) to (7), (8), (11) and (12) are mixed and heated to 70 ° C. B. Mix components (9), (10) and (13) and heat to 70 ° C.
Keep on. C. B was added to A, mixed and cooled to obtain a cream.

(Test method) Females aged 26 to 52 1
A panel consisting of 5 people was applied twice daily in the morning and at night twice on the face for 12 weeks, and then an appropriate amount of the test cream was applied to the face. The skin beautifying effect by application was evaluated according to the following criteria.

(Evaluation standard) Skin beautifying effect: [Evaluation] [Content] Effectiveness The dullness of the skin was not noticeable. Somewhat effective The dullness of the skin became less noticeable. Ineffective No change from before use.

[0122]

As is clear from the results shown in Table 17, the creams of the products 14 and 15 of the present invention were effective in preventing and improving the occurrence of "dullness" on the skin, and the skin-beautifying effect was recognized.

Example 20 Chemical lotion: A lotion was prepared by the following formulation and the following production method. (Method) Blending amount (%) (1) Glycerin 5.0 (2) 1,3-butylene glycol 6.5 (3) Polyoxyethylene sorbitan 1.2 Monolauric acid ester (20E.O.) (4) Ethyl alcohol 8.0 (5) Flodemanita extract ^* 1.0 (6) Collagen ^** 0.5 (7) Preservative proper amount (8) Perfume proper amount (9) Purified water residual amount * The one manufactured in Reference Example 1. ** Koken Co., Ltd.

(Production Method) A. Components (3), (4), (5), (7) and (8) are mixed and dissolved. B. Components (1), (2), (6) and (9) are mixed and dissolved. C. A and B were mixed and homogenized to obtain a lotion.

Example 21 Pack: A pack was prepared according to the following formulation and the following production method. (Method) Blending amount (%) (1) Polyvinyl alcohol 20.0 (2) Ethyl alcohol 20.0 (3) Glycerin 5.0 (4) Kaolin 6.0 (5) Flodemanita extract ^* . 5 (6) Sodium hyaluronate ^** 0.01 (7) Antiseptic 0.2 (8) Fragrance 0.05 (9) Purified water balance * The product produced in Reference Example 1. ** Made by QP Corporation

(Production Method) A. Components (1), (3), (4), (6) and (9) were mixed and mixed at 70 ° C.
Heat and stir. B. Mix components (2), (5), (7) and (8). C. The above B was added to the above A, mixed and cooled to obtain a pack.

Example 22 Cleaning Agent: A cleaning agent was prepared according to the following formulation and the following production method. (Method) Blending amount (%) (1) Stearic acid 10.0 (2) Palmitic acid 8.0 (3) Myristic acid 12.0 (4) Lauric acid 4.0 (5) Oleyl alcohol 1.5 ( 6) Purified lanolin 1.0 (7) Perfume 0.1 (8) Preservative 0.2 (9) Glycerin 18.0 (10) Potassium hydroxide 6.0 (11) Flow demanita extract ^* 0 .5 (12) Keratin hydrolyzed liquid ^** 0.05 (13) Residual amount of purified water * Prepared in Reference Example 1. ** Made by Seiwa Kasei Co., Ltd.

(Production Method) A. Components (9), (10) and (13) are mixed and heated to 70 ° C. B. Components (1)-(6), (8) and (11) are mixed and heated to 70 ° C. C. The above B was added to the above A, kept at 70 ° C for a while, cooled to 50 ° C after the saponification reaction was completed, and the components (7) and (1
2) was added and cooled to obtain a cleaning agent.

[0130]

EFFECTS OF THE INVENTION According to the present invention, the inherent performance of the medicinal agent can be fully exerted. For example, the external preparation for skin of the present invention containing an active oxygen scavenger or an antioxidant as a medicinal agent has an excellent active oxygen scavenging effect, improves skin roughness, and is stable and excellent in preventing skin aging. Therefore, it has an extremely high preventive effect against the production of lipid peroxide, inflammation, blackening, aging, etc. due to the production of active oxygen in the skin by ultraviolet rays. On the other hand, the external preparation for skin of the present invention containing a cell activating agent as a medicinal agent has an excellent cell activating action, so that skin aging prevention, trauma, cracks,
It is effective for improving cracks, sores, hemorrhoids, burns, and promoting wound healing.

Further, the external preparation for skin of the present invention containing an anti-inflammatory agent or a tyrosinase activity inhibitor as a medicinal agent is stable and has excellent anti-inflammatory and whitening effects, and is therefore highly effective for skin inflammation and pigmentation. It exerts a suppressing effect and is effective in preventing and improving blackening of the skin due to sunburn, stains and freckles. Furthermore, the external preparation for skin of the present invention containing a moisturizer as a medicinal agent is stable and has an excellent effect of improving rough skin, and therefore is effective for preventing and improving the occurrence of "dullness" of the skin. Thus, the skin external preparation of the present invention,
It is extremely useful in beauty and medicine because it can fully exhibit the inherent properties of a medicinal agent.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Internal reference number FI Technical display location A61K 7/00 H G J W 35/78 ADA 8217-4C (72) Inventor Akinori Hayashi Tokyo Metropolitan North 48-18 Sakaemachi-ku, Kose Research Institute Co., Ltd. (72) Inventor, Mariko Asai 48-18 Sakaemachi, Kita-ku, Tokyo Kose Research Institute Co., Ltd.

Claims (15)

[Claims] 1. The following components (A) and (B) (A) Flodemanita extract (B) Active oxygen scavenger, antioxidant, cell activator, anti-inflammatory agent, tyrosinase activity inhibitor and moisturizer. An external preparation for skin comprising one or more medicinal agents selected from the following. 2. The external preparation for skin according to claim 1, wherein the drug is an active oxygen scavenger. 3. The active oxygen scavenger is carotenoids such as SOD, mannitol, beta-carotene, hydroquinone, bilirubin, cholesterol, tryptophan,
The external preparation for skin according to claim 2, which is selected from plant extracts containing flavonoids such as histidine, quercetin, quercitrin, catechin, catechin derivatives, gallic acid, gallic acid derivatives, and augon extract in its components. . 4. The external preparation for skin according to claim 1, wherein the medicinal agent is an antioxidant. 5. Antioxidants include vitamins A and derivatives thereof and salts thereof, vitamins B and derivatives thereof and salts thereof, vitamin C and derivatives thereof and salts thereof, vitamins D and salts thereof. Derivatives and salts thereof, vitamin E and derivatives thereof and salts thereof, glutathione and derivatives thereof and salts thereof, B
The external preparation for skin according to claim 4, which is selected from HT and BHA. 6. The external preparation for skin according to claim 1, wherein the medicinal agent is a cell activating agent. 7. A cell activating agent is a deoxyribonucleic acid and a salt thereof, an adenylic acid derivative such as adenosine triphosphate and adenosine monophosphate and a salt thereof, ribonucleic acid and a salt thereof, guanine, xanthine and a derivative thereof, and them. -Related substances such as salt of sorghum; serum deproteinized extract, spleen extract, placenta extract, chicken cob extract, royal jelly and other animal-derived extracts; yeast extract, lactic acid bacterium extract, bifidobacteria extract, ganoderma lucidum Extracts derived from microorganisms such as extracts; carrot extract, assembly extract, rosemary extract, oat extract, garlic extract, hinokitiol, cepharanthin and other plant-derived extracts; α- or γ-linolenic acid, Eicosapentaenoic acid and derivatives thereof, succinic acid and derivatives thereof and salts thereof,
7. The external preparation for skin according to claim 6, which is selected from estradiol and its derivatives and salts thereof. 8. The external preparation for skin according to claim 1, wherein the medicinal agent is an anti-inflammatory agent. 9. The anti-inflammatory agent is glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene and their derivatives, and salts thereof, ε-aminocaproic acid, zinc oxide, diclofenac. Claims, which are selected from sodium, licorice extract, aloe extract, shikon extract, salvia extract, arnica extract, chamomile extract, birch extract, hypericum extract, eucalyptus extract and mukuroji extract. The external preparation for skin according to item 8. 10. The external preparation for skin according to claim 1, wherein the medicinal agent is a tyrosinase activity inhibitor. 11. A tyrosinase activity inhibitor comprises cysteine and its derivatives and salts thereof, soybean apricot extract, adzuki bean extract, ibukitranoo extract, clara extract, hawthorn extract, syringa lichen extract, hop extract, and Neubara extract. The external preparation for skin according to claim 10, which is selected from the extract and Yokuinin extract. 12. The external preparation for skin according to claim 1, wherein the medicinal agent is a moisturizing agent. 13. The external preparation for skin according to claim 12, wherein the moisturizing agent is a mucopolysaccharide or a protein. 14. The external skin preparation according to claim 13, wherein the mucopolysaccharide is selected from hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and keratan sulfate, and salts thereof. 15. The external preparation for skin according to claim 13, wherein the protein is selected from collagen, elastin, keratin, derivatives thereof and salts thereof.