JP2006348035A - Preparation suitable for external application - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a preparation the ingredients of which fully exhibit the pharmacological effects inherent in them and which is suitable for use in external applications such as cosmetics effective for beauty and health care and external medicines. <P>SOLUTION: The preparation contains ingredient (A); an astaxanthine and ingredient (B); one or more of efficacious agents selected from active oxygen removers, antioxidants, cell activators, antiphlogistics, tyrosinase inhibitors and humectants. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a composition suitable for external use, and more particularly to a composition suitable for external use such as cosmetics, external medicines, and the like, which contains an astaxanthin and a specific medicinal agent.

Conventionally, for the purpose of imparting a predetermined medicinal effect to cosmetics such as emulsions, creams, lotions, packs, dispersions, cleaning agents, and external medicines such as ointments, creams, and external liquids. Ingredients are added.
For example, calamine, ascorbic acids, glutathione, colloidal sulfur, hydroquinone, cinnamaldehyde, etc. are blended to prevent skin darkening and inflammation caused by sunburn, etc., and spots and freckles caused by pigmentation. In addition to improving rough skin, preventing skin aging, activating cells, treating wounds after cuts and shaving, improving wounds such as cracks, scratches, sores, hemorrhoids, and burns, allantoin, aloe Medicinal components such as extracts, carrot extracts, sicon extracts, placenta extracts, bovine blood deproteins, and fermented metabolites are blended.

  However, a composition suitable for external use such as cosmetics and external medicines containing these medicinal ingredients (hereinafter sometimes referred to as “external composition”) may not have sufficient effects of the medicinal ingredients or in the preparation. In many cases, the desired medicinal effect cannot be obtained due to alteration, and improvement has been desired.

  As a result of intensive studies to improve the effect of the medicinal component of the composition for external use, the present inventors have found that the action of the medicinal agent is sufficiently exhibited by combining astaxanthins and the medicinal agent, The present invention has been completed.

That is, the present invention provides the following components (A) and (B)
(A) Astaxanthins (B) A composition containing one or more medicinal agents selected from active oxygen scavengers, antioxidants, cell activators, anti-inflammatory agents, tyrosinase activity inhibitors and humectants. It is to provide.

According to the present invention, the inherent performance of a medicinal agent can be sufficiently exhibited. For example, the composition of the present invention containing an active oxygen scavenger or an antioxidant as a medicinal agent has an excellent active oxygen scavenging action, and has a stable and excellent effect for improving rough skin and preventing skin aging. Therefore, it has an extremely high preventive effect on the production of lipid peroxide, inflammation, blackening, aging, etc. caused by the generation of active oxygen in the skin by ultraviolet rays.
On the other hand, since the composition of the present invention containing a cell activator as a medicinal agent has an excellent cell activation effect, it prevents skin aging, improves trauma, cracks, bruises, sores, hemorrhoids, burns, etc., promotes wound healing Etc. are effective.

In addition, the composition of the present invention containing an anti-inflammatory agent or a tyrosinase activity inhibitor as a medicinal agent has a stable and excellent anti-inflammatory action and whitening action, and thus exhibits a high inhibitory effect on skin inflammation and pigmentation. In addition, it is effective in preventing or improving the blackening of the skin due to sunburn, spots, and freckles.
Furthermore, since the composition of the present invention containing a moisturizing agent as a medicinal agent has a stable and excellent skin roughness-improving action, it is effective for preventing and improving the occurrence of “dullness” of the skin.
As described above, the composition of the present invention can sufficiently exhibit the inherent performance of a medicinal agent, and thus is extremely useful in beauty and medicine.

  Astaxanthins, which are the component (A) of the composition of the present invention, already have an antioxidant effect, an anti-inflammatory effect (JP-A-2-49091), an anti-skin aging effect (JP-A-5-155536), a whitening effect (Nippon Incense) It is known to have the 19th Annual Scientific Congress of Cosmetic Science Society (P.66, 1994). These astaxanthins may be chemically synthesized products or may be extracted from natural products such as krill, salmon, trout, cypress, red yeast, etc., and for example, those prepared as follows can be preferably used.

  That is, an extraction solvent is added to and extracted from krill family krill (Euphausia similis GO, etc.), and the extract is obtained by filtering the extract, and the extraction solvent is further distilled off from the extract and hydrogenated as necessary. After performing chemical reaction such as addition or hydrolysis, purified astaxanthins that have been deodorized and purified by means of molecular distillation, column chromatography, high performance liquid chromatography (HPLC) or the like can be used.

  As said extraction solvent, organic solvents, such as acetone, ether, chloroform, alcohol (ethanol, methanol, etc.), can also be used, and these mixed solutions can also be used. Alternatively, supercritical carbon dioxide may be used.

で示されるカロテノイドであり、その誘導体としては、アスタキサンチンのエステルが挙げられ、例えば、グリシン、アラニン等のアミノ酸エステル類、酢酸エステル、クエン酸エステル等のカルボン酸エステル及びその塩類、リン酸エステル、硫酸エステル等の無機塩エステル及びその塩類、グルコシド等の配糖体類、またはエイコサペンタエン酸やドコサヘキサエン酸等の高度不飽和脂肪酸、オレイン酸やリノール酸等の不飽和脂肪酸またはパルミチン酸やステアリン酸等の飽和脂肪酸から選択される脂肪酸エステル類等から選択されるモノエステル体及び同種または異種のジエステル体等が挙げられる。 In addition, astaxanthin in this invention includes both astaxanthin and its derivative (s). Astaxanthin has the following formula

Derivatives thereof include, for example, esters of astaxanthin. Examples thereof include amino acid esters such as glycine and alanine, carboxylic acid esters such as acetate ester and citrate ester, and salts thereof, phosphate ester, sulfuric acid, and the like. Inorganic salt esters such as esters and salts thereof, glycosides such as glucoside, highly unsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, unsaturated fatty acids such as oleic acid and linoleic acid, or palmitic acid and stearic acid Examples thereof include monoesters selected from fatty acid esters selected from saturated fatty acids and the like, and the same or different diesters.

  The content of astaxanthins in the composition of the present invention is preferably 0.0001 to 5% by mass (hereinafter simply referred to as “%”), more preferably 0.0001 to 1%. When the extract is used, the concentration of the extract is not limited as long as the solute content is within the above range. If the content of this astaxanthin is less than 0.0001%, a sufficient effect may not be obtained, and even if it exceeds 5%, no further increase in the effect is observed.

  On the other hand, the medicinal agent 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. Examples of the agent include those shown below.

(Reactive oxygen scavenger and antioxidant)
Examples of the active oxygen scavenger include plant extracts containing flavonoids such as SOD, mannitol, hydroquinone, bilirubin, cholesterol, tryptophan, histidine, quercetin, quercitrin, gallic acid, gallic acid derivatives, ginkgo biloba extract, A gokahi extract, a yashajitsu extract, a dicoppi extract, etc. are mentioned.

  Antioxidants include, for example, vitamin A acetates such as vitamin A acetate and vitamin A palmitate and derivatives thereof, and salts thereof, vitamin Bs and derivatives thereof, and salts thereof, phosphoric acid-L-ascorbyl magnesium, L-ascorbic acid sulfate disodium, vitamin C such as vitamin C dipalmitate and derivatives thereof, and salts thereof, vitamin Ds and derivatives thereof, and salts thereof, vitamin E such as vitamin E acetate and derivatives thereof, and salts thereof , Glutathione and derivatives thereof, and salts thereof, BHT, BHA and the like.

  Among the active oxygen scavengers and antioxidants, mannitol, vitamin C and derivatives thereof and salts thereof, vitamin E and derivatives thereof and salts thereof are particularly preferable.

(Cell Activator)
Examples of the cell activator include adenylate derivatives such as deoxyribonucleic acid and salts thereof, adenosine triphosphate and adenosine monophosphate and salts thereof, ribonucleic acid and salts thereof, guanine, xanthine and derivatives thereof and salts thereof. Nucleic acid related substances such as: Serum deproteinized extract, spleen extract, placenta extract, poultry extract, royal jelly extract, etc .; yeast extract, lactic acid bacteria extract, bifidobacteria extract, ganoderma extract Extracts from microorganisms such as carrot extract, assembly extract, rosemary extract, buckwheat extract, garlic extract, hinokitiol, cephalanthin, etc .; α- or γ-linolenic acid, eicosapentaene Acids and derivatives thereof, succinic acid and derivatives thereof, and salts thereof, estradiol and derivatives thereof Derivatives and salts thereof, α-hydroxy acids such as lactic acid, glycolic acid, citric acid, malic acid, and salicylic acid and their derivatives and salts thereof can be mentioned.

  Among these cell activators, particularly preferred are deoxyribonucleic acid and salts thereof, adenosine triphosphate and salts thereof, serum deproteinized extract, placental extract, yeast extract, carrot extract, succinic acid and derivatives thereof. As well as their salts.

(Anti-inflammatory agent)
Anti-inflammatory agents include glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene and their derivatives and their salts, ε-aminocaproic acid, zinc oxide, diclofenac sodium, aloe extraction Products, salvia extract, arnica extract, chamomile extract, birch extract, hypericum extract, eucalyptus extract, mukuroji extract and the like.

  Among these anti-inflammatory agents, particularly preferred are glycyrrhizic acid, glycyrrhetinic acid, guaiazulene and derivatives thereof, and salts thereof, ε-aminocaproic acid, aloe extract, chamomile extract.

(Tyrosinase activity inhibitor)
Examples of tyrosinase activity inhibitors include cysteine and derivatives thereof (for example, N, N′-diacetylcystine dimethyl, etc.) and salts thereof, Sempukuka extract, quette extract, sunpens extract, Sohakuhi extract, Toki extract, Ibukitorano extract Products, Clara extract, hawthorn extract, white lily extract, hop extract, Neubara extract, Yokuinin extract and the like.

(Humectant)
As the moisturizing agent, mucopolysaccharides and / or proteins that are constituents of the skin and are conventionally blended in cosmetics can be used.

  Among these, examples of the mucopolysaccharide include hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and keratan sulfate, and salts thereof. Hyaluronic acid, chondroitin sulfate, and salts thereof can be preferably used. .

Examples of the protein include collagen, elastin, keratin and derivatives thereof, and salts thereof, and collagen is particularly preferable.
There is no restriction | limiting in particular about the origin of each of these components, Any of animal origin, microorganism origin, and a synthetic product may be sufficient. There are no particular restrictions on the extraction method and the purification treatment method in the case of natural origin.

  The compounding amount of the medicinal agent as the component (B) in the composition of the present invention varies depending on the kind of medicinal agent, but is preferably in the following range.

  That is, the active oxygen scavenger is generally added to the composition in an amount of 0.0001 to 5%, preferably 0.001 to 3%. When the amount of the active oxygen scavenger is less than 0.0001%, a sufficient effect may not be obtained, and even if it exceeds 5%, no further increase in the effect is observed. On the contrary, adverse effects may occur in terms of formulation. These active oxygen scavengers can be used singly or in combination of two or more.

  Antioxidants are also generally added to the composition in an amount of 0.0001 to 5%, preferably 0.001 to 3%. When the blending amount of the antioxidant is larger or smaller than the above range, it is not preferable for the same reason as described for the active oxygen removing agent. These antioxidants can also be used alone or in combination.

  The cell activator is preferably added to the composition in an amount of 0.001 to 5%, particularly preferably 0.01 to 3% from the viewpoint of stability over time, and may be used alone or in combination of two or more.

  The anti-inflammatory agent is generally 0.0001 to 5%, preferably 0.01 to 3% in the composition. Each of the anti-inflammatory agents can be used alone or in combination of two or more.

  Furthermore, the tyrosinase activity inhibitor is preferably blended so that the content in the composition is 0.0001 to 10%, particularly 0.001 to 5% as a dry solid content. If it is less than 0.0001%, a sufficient whitening effect cannot be obtained, and if it exceeds 10%, the effect does not increase. In some cases, problems such as coloring of the product may occur, which is not preferable. In addition, these can be used 1 type or in combination of 2 or more types.

  Furthermore, the blending amount of mucopolysaccharide and / or protein as a humectant in the composition of the present invention is generally 0.0001 to 5%, preferably 0.001 to 3%. If these contents are less than 0.0001%, a sufficient effect may not be obtained, and even if it exceeds 5%, no further increase in the effect is observed. These mucopolysaccharides and proteins can also be used singly or in combination.

  The composition of the present invention can be prepared by blending essential components (A) and (B) with various forms of bases known as ordinary external compositions in accordance with conventional methods.

  Examples of the form of the composition are not particularly limited. For example, cosmetics such as emulsions, creams, lotions, packs, dispersions, cleaning agents, makeup cosmetics, scalp / hair products, ointments, creams, As a base for an external composition, a base according to the form of these external preparations, for example, purified water, lower alcohol, polyhydric alcohol, fats and oils, surfactant, Ultraviolet absorbers, thickeners, pigments, preservatives, fragrances and the like can be used.

  Next, although a reference example, a test example, and an Example are given and this invention is demonstrated further in detail, this invention is not restrict | limited at all to these.

Reference example 1
Astaxanthin extraction:
500 ml of acetone was added to 100 g of dried krill shells (astaxanthin content: 223 mg%), and extraction was performed with stirring for 1 hour. Thereafter, the filtrate obtained by suction filtration was concentrated under reduced pressure using an evaporator, and the obtained concentrated solution was dried under reduced pressure to obtain 15 g of an astaxanthin extract (astaxanthin content: 1.3%).

Reference example 2
Purification of astaxanthins:
Column chromatography was performed on 10 g of the extract obtained in Reference Example 1. That is, the extract was adsorbed on a glass column filled with silica gel and having an inner diameter of 3 cm and a height of 20 cm, and impurities were eluted with 500 ml of n-hexane, and then astaxanthins were eluted with acetone. The eluate was concentrated under reduced pressure using an evaporator and further subjected to steam distillation to obtain 0.8 g of purified astaxanthins (astaxanthin content: 14.6%).

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

Absorbance (B) of the sample in which purified water was added instead of the test sample for the control, and 0.1 ml of xanthine oxidase was added to the blank of each sample after adding 0.1 ml of 6 mM CaCl ₂ and stopping the reaction. The superoxide removal rate was calculated from the following formula. The results are shown in Table 1.

Ａ： 試料の酵素反応による吸光度
Ｂ： 対照の酵素反応による吸光度
Ｃ： 試料の無酵素反応による吸光度

A: Absorbance due to enzyme reaction of sample
B: Absorbance by control enzyme reaction
C: Absorbance due to enzyme-free reaction of sample

（注）表中の、アスタキサンチン類、ＳＯＤ及びイチョウ抽出物の数字は、
それぞれの試料０.１ｍｌ中の重量（μｇ）を表わす。
*1 参考例２で製造したもの。
*2 シグマ社製；ウシ赤血球より得たもの（3.570 units/mg）。
*3 イチョウ葉１０部に５０V/V％エタノール水溶液５０部を加え、室温で３
日間抽出した後濾過したもの。

(Note) The numbers of astaxanthins, SOD and Ginkgo biloba extract in the table are
It represents the weight (μg) in 0.1 ml of each sample.
* 1 Manufactured in Reference Example 2.
* 2 Sigma; obtained from bovine erythrocytes (3.570 units / mg).
* 3 Add 50 parts of 50V / V% ethanol aqueous solution to 10 parts of ginkgo biloba leaves and add 3 parts at room temperature.
Filtered after extraction for days.

  As is clear from the results in Table 1, the astaxanthins obtained in Reference Example 2 alone had an SOD-like action, but when used in combination with SOD or a ginkgo biloba extract, exhibited a synergistic action. It has been shown to be extremely effective in removing active oxygen.

  This is because the composition of the present invention in which an astaxanthin and an active oxygen scavenger are used in combination is extremely high for the formation of lipid peroxide, inflammation, blackening, and aging caused by the generation of active oxygen in the skin by ultraviolet rays. It shows that it has a preventive effect.

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

*1 参考例２で製造したもの
*2 和光純薬社製 (Composition)

* 1 Manufactured in Reference Example 2
* 2 Wako Pure Chemical Industries

(Production method)
A. Ingredients (7), (9) and (13) are heated and mixed and maintained at 70 ° C.
B. Ingredients (1) to (6), (8) and (10) are heated and mixed and maintained at 70 ° C.
C. Add B above to A and mix, add component (12) and uniformly emulsify, 30 ° C
Cool to temperature, add component (11) and mix uniformly to obtain an emulsion.

( Test method )
For each test milk, 15 females aged 26 to 50 years were used as panels, and an appropriate amount of test milk was applied to the face after washing the face twice a day in the morning and night for 12 weeks. The effect of preventing skin aging and skin aging by application was evaluated according to the following criteria.

Beautiful skin effect:
[Evaluation] [Contents]
Effective Skin dullness is not noticeable.
Slightly effective Skin dullness is less noticeable.
Invalid No change before use.

Skin aging prevention effect:
[Evaluation] [Contents]
Effective Skin elasticity and gloss have been improved.
Slightly effective Skin elasticity and gloss were slightly improved.
Invalid No change before use.

(Result)

  As shown in the results of Table 3, by applying to the skin a composition comprising astaxanthins typified by the product 1 of the present invention and an antioxidant, skin dullness and the like can be suppressed and beautiful skin can be obtained. It has become clear that the beam and gloss have been improved and that skin aging has been prevented.

Example 2
Cream:
Creams were prepared by the composition shown in Table 4 and the following production method, and the skin beautifying effect and skin aging preventing effect were examined. The results are shown in Table 5.

*1 参考例２で製造したもの
*2 日光ケミカルズ社製
*3 和光純薬社製 (Composition)

* 1 Manufactured in Reference Example 2
* 2 Nikko Chemicals
* 3 Wako Pure Chemical Industries

(Production method)
A. Ingredients (1)-(8), (11) and (12) are mixed and heated to keep at 70 ° C.
B. Ingredient (13) is heated and maintained at 70 ° C.
C. B was added to A, mixed, then cooled, (9) and (10) were added, and mixed uniformly to obtain a cream.
(Test method) Same as Example 1 (Evaluation criteria) 〃

(Result)

  As shown in the results in Table 5, by applying a composition comprising a combination of astaxanthins represented by the present invention products 2 and 3 and an antioxidant or an active oxygen remover to the skin, skin dullness and the like are suppressed, It became clear that the skin became beautiful and the skin elasticity and gloss were improved, preventing skin aging.

Example 3
Cosmetic water:
(Treatment) Blending amount (%)
(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) Astaxanthins * 1 0.0005
(6) SOD * 2 0.5
(7) Preservative proper amount (8) Perfume proper amount (9) Refining water remaining amount
* 1 Manufactured in Reference Example 2.
* 2 Manufactured by Sigma; obtained from human red blood cells (5.230 units / mg)

(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 uniformed to obtain a skin lotion.

Example 4
Pack:
(Treatment) Blending amount (%)
(1) Polyvinyl alcohol 20.0
(2) Ethyl alcohol 20.0
(3) Glycerin 5.0
(4) Kaolin 6.0
(5) Astaxanthins * 1 0.05
(6) Ginkgo biloba extract * 2 0.2
(7) Preservative 0.2
(8) Fragrance 0.1
(9) Remaining amount of purified water
* 1 Manufactured in Reference Example 2
* 2 Add 50 parts of 50V / V% ethanol aqueous solution to 10 parts of ginkgo biloba leaves and add 3 parts at room temperature.
Filtered after extraction for days.

(Production method)
A. Ingredients (1), (3), (4) and (9) are mixed, heated to 70 ° C. and stirred.
B. Ingredients (2), (5), (7) and (8) are mixed.
C. The above B was added to the above A, mixed and then cooled to uniformly disperse (6) to obtain a pack.

Example 5
Cleaning fee:
(Treatment) 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) Fragrance 0.1
(8) Preservative 0.2
(9) Glycerin 18.0
(10) Potassium hydroxide 6.0
(11) Astaxanthins * 1 0.5
(12) Acetic acid-dl-α-0.05
Tocopherol * 2
(13) Remaining amount of purified water
* 1 Manufactured in Reference Example 2
* 2 Sigma

(Production method)
A. Ingredients (9), (10) and (13) are mixed and heated to 70 ° C.
B. Components (1) to (6), (8), (11) and (12) are mixed and heated to 70 ° C.
C. The above B is added to the previous A and kept at 70 ° C. for a while. After the saponification reaction is completed, 50 ° C.
The mixture was cooled to component (7) and cooled to obtain a cleaning material.

Example 6
Lipstick:
Lipstick was prepared by the following formulation and manufacturing method.
(Treatment) Blending amount (%)
(1) Astaxanthins * 1 0.02
(2) Ergocalciferol * 2 0.02
(3) Red No. 202 0.2
(4) Candelilla Row 9.0
(5) Solid paraffin 8.0
(6) Beeswah 5.0
(7) Carnauba 5.0
(8) Lanolin 11.0
(9) Isopropyl myristate 10.0
(10) Remaining amount of refined castor oil
* 1 Manufactured in Reference Example 2
* 2 Wako Pure Chemical Industries

(Production method)
A. Components (4) to (10) are heated and dissolved, and then kneaded with three rollers.
B. After adding components (1) to (3), knead again twice with three rollers.
C. Cool and mold to get lipstick.

Test example 2
Wound healing test:
Wistar male rats aged 8 weeks were used for the experiment as 10 rats per group. After shaving the back of the rat, under anesthesia, the left and right dorsal skins were incised over 4 cm so as to be symmetric with respect to the midline, with one serving as the drug application site and the other serving as the control site. Immediately after the incision, the three incision sites were sutured and wiped with disinfecting ethanol. Any one of the present invention products 4 to 6 and comparative products 8 to 11 (dissolved in physiological saline) shown in Table 6 is used for the drug application site in the sutured portion, and physiological saline is used for the control site. Of 0.1 ml was applied twice a day for one week.

One week later, the dorsal skin was peeled off, a strip-shaped section was created around the incision, and the tensile strength of the skin section was measured using a rheometer NRM-2002J (manufactured 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.

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

  As shown in the results of Table 6, when the composition of the present invention in which astaxanthins and a cell activator such as ATP, placenta extract, yeast extract and the like are combined is applied to the skin, the wound healing rate is high, It was revealed that trauma, cracks, bruises, sores, hemorrhoids, burns, etc. can be effectively improved and treated.

Example 7
Cream:
Creams were prepared by the composition shown in Table 7 and the following production method, and the skin beautifying effect and skin aging preventing effect were examined. The results are shown in Table 8.

*1 参考例２で製造したもの
*2 三省製薬社製
*3 ペンタファーム社製 (Composition)

* 1 Manufactured in Reference Example 2
* 2 Sansho Pharmaceutical Co., Ltd.
* 3 Made by Penta Farm

(Production method)
A. Ingredients (1)-(8), (11) and (12) are mixed and heated to keep at 70 ° C.
B. Ingredients (9), (10) and (13) are mixed and heated to keep at 70 ° C.
C. B was added to A, mixed, and cooled to 30 ° C. to obtain a cream.

( Test method )
For each test cream, 15 females aged 28 to 54 years were used as panels, and an appropriate amount of the test cream was applied to the face after washing the face twice a day in the morning and night for 12 weeks. The effect of preventing beautiful skin and skin aging by application was evaluated according to the same criteria as in Example 1. The results are shown in Table 8.

(Result)

  As shown in the above results, the composition of the present invention containing astaxanthins typified by the products 7 and 8 of the present invention and a cell activator suppresses dullness of the skin by applying this to the skin, It became clear that the skin became beautiful and the skin elasticity and gloss were improved, preventing skin aging.

Example 8
Cosmetic water:
(Treatment) Blending amount (%)
(1) Polyoxyethylene (60E.O.) hydrogenated castor oil 1.0
(2) Ethanol 15.0
(3) Preservative 0.1
(4) Hinokitiol 0.01
(5) Fragrance appropriate amount (6) Astaxanthins * 0.01
(7) Citric acid 0.1
(8) Sodium citrate 0.3
(9) 1,3-butylene glycol 4.0
(10) The amount of purified water remaining
* Manufactured in Reference Example 2.

(Production method)
A. Components (1) to (6) are heated, mixed and dissolved.
B. Components (7) to (10) are heated, mixed and dissolved.
C. A lotion was obtained by mixing A and B.

Example 9
Milk liquid:
(Treatment) Blending amount (%)
(1) Polyoxyethylene (10E.O.) 1.0
Sorbitan monostearate (2) Polyoxyethylene (60E.O.) 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) Astaxanthins * 0.1
(10) Carboxyvinyl polymer 0.1
(11) Sodium hydroxide 0.05
(12) Ethyl alcohol 5.0
(13) Amount of purified water remaining (14) Appropriate amount of perfume
* Manufactured in Reference Example 2.

(Production method)
A. Ingredients (10) to (13) are heated and mixed and maintained at 70 ° C.
B. Ingredients (1) to (9) are heated and mixed and maintained at 70 ° C.
C. A is added to B, mixed and uniformly emulsified.
D. After cooling C, (14) was added and mixed uniformly to obtain an emulsion.

Example 10
Ointment:
(Treatment) Blending amount (%)
(1) Stearic acid 18.0
(2) Cetanol 4.0
(3) Triethanolamine 2.0
(4) Glycerin 5.0
(5) Astaxanthins * 1 1.0
(6) Milk acid * 2 1.0
(7) Purified water balance
* 1 Manufactured in Reference Example 2
* 2 Wako Pure Chemical Industries

(Production method)
A. A part of components (3), (4) and (7) are heated and mixed and kept at 75 ° C.
B. Ingredients (1), (2) and (5) are heated and mixed and maintained at 75 ° C.
C. Gradually add A to B.
D. (6) dissolved in the remainder of (7) was added while cooling C to obtain an ointment.

Test example 3
Anti-inflammatory and whitening effects:
A skin lotion containing the chemicals shown in Table 9 and ethanol 15% (v / v), the balance being purified water, was prepared and applied to the back of colored guinea pigs to examine the effects on sunburn-induced inflammation and pigmentation. The results are shown in Table 10.

( Test method )
The backs of colored guinea pigs (10 per group) were shaved and irradiated with ultraviolet rays under anesthesia. In the ultraviolet irradiation, three FL20S / BLB lamps and three FL20S / E30 lamps manufactured by Toshiba Corporation were simultaneously irradiated, and the amount of ultraviolet light was 4.8 × 10 ⁴ erg / cm ² . Samples were thoroughly rubbed in 0.2 ml each at 4 locations on the back of the guinea pig 24 hours before UV irradiation, immediately after irradiation, 12 hours after irradiation, and 24 hours after irradiation. The application site was thoroughly washed with warm water before ultraviolet irradiation. The degree of inflammation was observed 24 hours after irradiation and the degree of pigmentation after 7 days.

*1 参考例２で製造したもの。
*2 丸善製薬社製
*3 和光純薬社製
*4 丸善製薬社製

* 1 Manufactured in Reference Example 2.
* 2 Made by Maruzen Pharmaceutical Co., Ltd.
* 3 Wako Pure Chemical Industries
* 4 Made by Maruzen Pharmaceutical Co., Ltd.

( Evaluation criteria )
Evaluation criteria for inflammation (anti-inflammatory effect)
0: No inflammation is observed 1: Very little inflammation is observed 2: Inflammation is observed but the boundary with the non-irradiated part is unclear 3: Inflammation is observed, and the boundary with the non-irradiated part is clear

Evaluation criteria for pigmentation (whitening effect)
0: No pigmentation is observed 1: Very little pigmentation is observed 2: Pigmentation is observed, but the boundary with the non-irradiated part is unclear 3: The pigmentation is observed, the boundary with the non-irradiated part Clear

  According to the above evaluation criteria, the number of guinea pigs each having a score of 1 or less was counted out of 10 and judged according to the following criteria.

(Criteria)
[Judgment] [contents]
Efficacy Among 10 animals, the number of guinea pigs with a score of 1 or less is 8 or more.
Effectiveness Of 10 animals, the number of guinea pigs with a score of 1 or less is 6 or more.
Slightly effective Among 10 animals, the number of guinea pigs with a score of 1 or less is 4 or more.
Ineffective 10 out of 10 guinea pigs with a score of 1 or less.

  From the results of Table 10, the composition of the present invention containing an astaxanthin and an anti-inflammatory agent such as dipotassium glycyrrhizinate, guaiazulene, and aloe extract suppresses skin inflammation and pigmentation when applied to the skin. It became clear.

Example 11
Cream:
A cream was prepared by the following formulation and the following production method.
(Treatment) Blending 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) Astaxanthins * 2 0.5
(12) Amount of purified water remaining (13) Appropriate amount of perfume
* 1 Made by Maruzen Pharmaceutical Co., Ltd.
* 2 Manufactured in Reference Example 2.

(Production method)
A. Components (1) to (7) and (11) are dissolved by heating at 70 ° C.
B. Components (8) to (10) and (12) are dissolved by heating at 70 ° C.
C. Add A to B and emulsify.
D. Ingredient (13) is added to C and cooled to obtain a cream.

Example 12
Milk liquid:
An emulsion was prepared by the following formulation and the following production method.
(Treatment) Blending 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) Astaxanthins * 1 1.0
(10) Aloe extract * 2 0.2
(11) Methylparaben 0.1
(12) Carboxyvinyl polymer 0.07
(13) 1,3-butylene glycol 5.0
(14) purified water remaining amount (15) sodium hydroxide 0.025
(16) Refined water 7.5
(17) Perfume appropriate amount
* 1 Manufactured in Reference Example 2.
* 2 Made by Maruzen Pharmaceutical Co., Ltd.

(Production method)
A. Components (1) to (9) are dissolved by heating at 70 ° C.
B. Components (10) to (14) are dissolved by heating at 70 ° C.
C. Add A to B and emulsify.
D. Add (15) to (17) to C and cool to obtain an emulsion.

Example 13
Cosmetic lotion:
A lotion was prepared by the following formulation and the following production method.
(Treatment) Blending amount (%)
(1) Polyoxyethylene hydrogenated castor oil (60E.O) 1.0
(2) Perfume appropriate amount (3) Ethanol 10.0
(4) Methylparaben 0.1
(5) Chamomile extract * 2 0.3
(6) Citric acid 0.1
(7) Sodium citrate 0.3
(8) 1,3-butylene glycol 5.0
(9) Astaxanthins * 1 0.01
(10) Amount of purified water remaining
* 1 Manufactured in Reference Example 2.
* 2 Made by Ichimaru Falcos

(Production method)
A. Components (1) to (4) and (9) are mixed and dissolved.
B. Components (5) to (8) and (10) are mixed and dissolved.
C. B is added to A and stirred to obtain a lotion.

Reference example 3
Production of plant extracts:
Add 100 ml of 70% (v / v) ethyl alcohol to each 10 g of Sohakuhi (Japan), Kujin (Clara) (Japan), Toki (Japan), and Hop (Hanaho). Each plant extract was obtained by extracting for a day and filtering.

Test example 4
Tyrosinase activity inhibition test:
By the following method, the 0.5% (W / V) solution of the extract obtained in Reference Example 2 and the extract obtained in Reference Example 3 were examined for the tyrosinase activity inhibition rate of a single sample or a combination thereof.
That is, 0.1 ml of an enzyme solution [manufactured by Sigma, 10 mg of 28,000 units of tyrosinase dissolved in 20 ml of 0.1 M phosphate buffer (pH 6.8)] was added to each sample, and 0.1 M phosphoric acid was further added. Buffer solution (pH 6.8) was added to make 4.0 ml, which was incubated at 25 ° C. for 10 minutes.

Next, 1.0 ml of a substrate solution [L-DOPA (Tokyo Kasei) 198.0 mg dissolved in 100 ml of 0.1 M phosphate buffer (pH 6.8)] previously maintained at 25 ° C. was added thereto, The reaction was allowed for 10 minutes. After the reaction, the absorbance at 475 nm (OD _S ) was measured.
Similarly, the absorbance (OD _HE ) when reacted using the enzyme deactivated by heating and the absorbance (OD _B ) when no sample was added were calculated, and the activity inhibition rate of tyrosinase activity was calculated from the following equation: did.

ＯＤ_S ： 試料吸光度
ＯＤ_B ： 試料無添加時の吸光度
ＯＤ_HE ： 酵素不活性時の吸光度
この結果を表１１に示す。

OD _S : Sample absorbance
OD _B: no sample is added at the time of the absorbance
OD _HE : Absorbance when the enzyme is inactive Table 11 shows the results.

* 参考例２で製造したもの。

* Manufactured in Reference Example 2.

As is apparent from Table 11, when astaxanthins and tyrosinase activity inhibitors were combined, the tyrosinase activity inhibitory action was higher than when astaxanthins or tyrosinase activity inhibitors were used alone, and showed a synergistic whitening effect. .
Therefore, the composition of the present invention combining the astaxanthins and the tyrosinase activity inhibitor exhibits an extremely excellent tyrosinase activity inhibitory action by applying this to the skin, and the skin blackening due to sunburn, stains, Effectively suppress buckwheat etc.

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

*1 参考例２で製造したもの
*2 システイン（和光純薬社製）を１.０ｍｇ／ｍｌの濃度になるように水で希
釈して、用いた。
*3 参考例３で製造したもの。

* 1 Manufactured in Reference Example 2
* 2 Cysteine (manufactured by Wako Pure Chemical Industries, Ltd.) was used after diluting with water to a concentration of 1.0 mg / ml.
* 3 Manufactured in Reference Example 3.

<Production method>
A. (6) to (10), (14) and (15) are heated and mixed and kept at 70 ° C.
B. (1) to (5), (11) and (12) are heated and mixed and kept at 70 ° C.
C. Add B to A and mix, add (13), emulsify uniformly, and cool to 30 ° C. to obtain an emulsion.

<Whitening effect test>
For each test milk product, 15 females aged 25 to 50 years were used as panels, and each day, morning and night twice, after the face was washed, the test milk was applied to the face for 12 weeks, and a usage test was conducted. Evaluation was made according to the following criteria.
Evaluation criteria;
Effective: Spots and freckles are not noticeable.
Slightly effective: Spots and freckles are less noticeable.
Invalid: Does not change.

As is clear from Table 13, the products 12 and 13 of the present invention containing a combination of astaxanthins and a tyrosinase activity inhibitor were not only compared with the comparative product 20 containing no these, but also astaxanthins or tyrosinase activity was inhibited. Even compared with Comparative Products 21 to 23, which contained the agent alone, it was excellent in the effect of making spots and freckles inconspicuous and showed a remarkable whitening effect.
Therefore, by applying to the skin the composition of the present invention containing a combination of astaxanthins and a tyrosinase activity inhibitor, it is possible to suppress spots, freckles and the like.

Example 15
Cosmetic water:
<Method> Blending amount (%)
(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) Astaxanthins * 1 0.01
(6) Yokuinin extract * 2 (as dry solid) 0.05
(7) Preservative appropriate amount (8) Perfume proper amount (9) Purified water remaining amount
* 1 Manufactured in Reference Example 2.
* 2 Made by Maruzen Pharmaceutical Co., Ltd.

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

Example 16
cream:
<Method> Blending amount (%)
(1) Beeswah 6.0
(2) Cetanol 5.0
(3) Reduced lanolin 5.0
(4) Squalane 30.0
(5) Glycerol monostearate 4.0
(6) Lipophilic glyceryl monostearate 2.0
(7) Polyoxyethylene sorbitan 2.0
Monolaurate (20E.O.)
(8) Astaxanthins * 1 1.0
(9) Sakuhakuhi extract * 2 (as dry solids) 0.2
(10) Preservative 0.3
(11) Fragrance 0.05
(12) Residual amount of purified water * 1 Produced in Reference Example 2 * 2 Made by Maruzen Pharmaceutical Co., Ltd.

<Production method>
A. (1) to (8), (10) and (11) are mixed, heated and kept at 70 ° C.
B. (9) and (12) are mixed and heated to keep at 70 ° C.
C. B was added to A, mixed, and then cooled to obtain a cream.

Example 17
Cleaning fee:
<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) Fragrance 0.1
(8) Preservative 0.2
(9) Glycerin 18.0
(10) Potassium hydroxide 6.0
(11) Astaxanthins * 1 0.2
(12) Hop extract * 2 0.01
(13) Residual amount of purified water
* 1 Manufactured in Reference Example 2.
* 2 Made by Koei Kogyo Co., Ltd.

<Production method>
A. (9), (10) and (13) are mixed and heated to 70 ° C.
B. (1) to (6), (8) and (11) are mixed and heated to 70 ° C.
C. B was added to A and kept at 70 ° C. for a while. After the saponification reaction was completed, the mixture was cooled to 50 ° C., (7) and (12) were added, and cooled to obtain a washing material.

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

*1 参考例２で製造したもの。
*2 日光ケミカルズ製
*3 高研製 (Composition)

* 1 Manufactured in Reference Example 2.
* 2 Made by Nikko Chemicals
* 3 Made by Koken

(Production method)
A. The components (6), (8) to (10) and (14) are heated and mixed and kept at 70 ° C.
B. The components (1) to (5), (7), (11) and (12) are heated and mixed and maintained at 70 ° C.
C. Add B above to A and mix, add component (13) and uniformly emulsify, 30 ° C
Was cooled to obtain an emulsion.

( Test method )
For each test emulsion, 15 healthy individuals aged 24 to 45 years were used as panels, and the skin condition before causing experimental rough skin was photographed with a microscope camera, and the score was determined according to the following criteria. Experimental rough skin was induced by treating the upper arm flexor side with a mixture of ether and acetone (1: 1). Thereafter, the test milk was applied twice a day in the morning and at night every day for 7 days, and the score of the skin condition was determined as described above 3, 5 and 7 days after the occurrence of rough skin.

Skin condition score:
[Score] [State]
1 Skin gaps are unclear and exfoliation of the skin is observed.
2 The skin groove is slightly unclear or strong in one direction.
3 Skin crevices are observed, but shallow or unidirectional.
4 Skin crevices are observed or are somewhat reticulated.
5 Skin gaps are clearly visible or have a fine mesh.

(Result)

  As shown in the results of Table 15, the composition of the present invention in which astaxanthin typified by the product 14 of the present invention and mucopolysaccharide are combined, and the composition of the present invention in which the astaxanthin typified by the product 15 of the present invention is combined with protein. It became clear that the rough skin can be improved by applying them to the skin.

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

*1 参考例２で製造したもの
*2 生化学工業社製
*3 一丸ファルコス社製 (Composition)

* 1 Manufactured in Reference Example 2
* 2 Made by Seikagaku Corporation
* 3 Made by Ichimaru Falcos

(Production method)
A. Ingredients (1)-(8), (11) and (12) are mixed and heated to keep at 70 ° C.
B. Ingredients (9), (10) and (13) are mixed and heated to keep at 70 ° C.
C. B was added to A, mixed, and then cooled to obtain a cream.

( Test method )
For each test cream, 15 women aged 27 to 54 years were used as a panel, and an appropriate amount of the test cream was applied to the face after face washing twice a day in the morning and at night for 12 weeks. The skin beautifying effect by application was evaluated according to the following criteria.

( Evaluation criteria )
Beautiful skin effect:
[Evaluation] [Contents]
Effective Skin dullness is not noticeable.
Slightly effective Skin dullness is less noticeable.
Invalid No change before use.

(Result)

  As shown in the results of Table 17, the composition of the present invention in which astaxanthin represented by the product 16 of the present invention and mucopolysaccharide are combined, and the composition of the present invention in which the astaxanthin represented by the product 17 of the present invention is combined with protein. It was revealed that by applying these to the skin, the occurrence of “dullness” of the skin can be prevented and improved, and beautiful skin can be obtained.

Example 20
Cosmetic water:
A lotion was prepared by the following formulation and the following production method.
(Treatment) Blending amount (%)
(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) Astaxanthins * 1 0.005
(6) Collagen * 2 0.5
(7) Preservative proper amount (8) Perfume proper amount (9) Refining water remaining amount
* 1 Manufactured in Reference Example 2.
* 2 Made by Koken

(Production method)
A. Components (3) to (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 uniformed to obtain a skin lotion.

Example 21
Pack:
A pack was prepared by the following formulation and the following production method.
(Treatment) Blending amount (%)
(1) Polyvinyl alcohol 20.0
(2) Ethyl alcohol 20.0
(3) Glycerin 5.0
(4) Kaolin 6.0
(5) Astaxanthins * 1 0.5
(6) Sodium hyaluronate * 2 0.01
(7) Preservative 0.2
(8) Perfume 0.05
(9) Remaining amount of purified water
* 1 Manufactured in Reference Example 2.
* 2 Made by Kewpie

(Production method)
A. Ingredients (1), (3), (4), (6) and (9) are mixed, heated to 70 ° C. and stirred.
B. Ingredients (2), (5), (7) and (8) are mixed.
C. The above B was added to the previous A, mixed, and then cooled to obtain a pack.

Example 22
Cleaning fee:
A cleaning material was prepared by the following formulation and the following production method.
(Treatment) 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) Fragrance 0.1
(8) Preservative 0.2
(9) Glycerin 18.0
(10) Potassium hydroxide 6.0
(11) Astaxanthins * 1 0.5
(12) Keratin hydrolyzate * 2 0.05
(13) Remaining amount of purified water
* 1 Manufactured in Reference Example 2.
* 2 Seiwa Kasei

(Production method)
A. Ingredients (9), (10) and (13) are mixed and heated to 70 ° C.
B. Components (1) to (6), (8) and (11) are mixed and heated to 70 ° C.
C. Add B above to A above and keep at 70 ° C for a while.
It cooled to 0 degreeC, the component (7) and (12) was added, and it cooled and obtained the washing | cleaning material.

Example 23
Hair tonic:
A hair tonic was prepared by the following formulation and the following production method.
(Treatment) Blending amount (%)
(1) Astaxanthins * 1 0.1
(2) Chamomile extract * 2 0.3
(3) Menthol 0.1
(4) Ethanol 40.0
(5) Appropriate amount of fragrance (6) Remaining amount of purified water
* 1 Manufactured in Reference Example 2.
* 2 Made by Ichimaru Falcos

(Production method)
A. Components (1) and (3) to (5) are mixed and dissolved.
B. Ingredients (2) and (6) are mixed and dissolved.
C. A was added to B and mixed uniformly to obtain a hair tonic.
more than

Claims (18)

Next components (A) and (B)
(A) Astaxanthins (B) containing one or more medicinal agents selected from active oxygen scavengers, antioxidants, cell activators, anti-inflammatory agents, tyrosinase activity inhibitors and humectants And a composition.   The composition according to claim 1, wherein the medicinal agent is an active oxygen scavenger.   A plant extract or gokahi extract whose active oxygen scavenger contains flavonoids such as SOD, mannitol, hydroquinone, bilirubin, cholesterol, tryptophan, histidine, quercetin, quercitrin, gallic acid, gallic acid derivatives, ginkgo biloba extract 3. The composition according to claim 2, wherein the composition is selected from a yashajtsu extract and a dicoppi extract.   The composition according to claim 1, wherein the medicinal agent is an antioxidant.   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, vitamin Ds and derivatives thereof and salts thereof 5. The composition according to claim 4, wherein the composition is selected from vitamin E and derivatives thereof and salts thereof, glutathione and derivatives thereof and salts thereof, BHT and BHA.   The composition according to claim 1, wherein the medicinal agent is a cell activator.   Cell activators include nucleic acids such as deoxyribonucleic acid and salts thereof, adenylic acid derivatives and salts thereof such as adenosine triphosphate and adenosine monophosphate, ribonucleic acid and salts thereof, guanine, xanthine and derivatives thereof and salts thereof Related substances: Serum deproteinized extract, spleen extract, placenta extract, chicken crown extract, royal jelly and other animal-derived extracts; yeast extract, lactic acid bacteria extract, bifidobacteria extract, ganoderma extract and other microorganisms Extracts from plants; extracts from plants such as carrot extract, assembly extract, rosemary extract, buckwheat extract, garlic extract, hinokitiol, cephalanthin; α- or γ-linolenic acid, eicosapentaenoic acid and the like Derivatives, succinic acid and its derivatives and their salts, estradiol and its derivatives and 7. The composition according to claim 6, which is selected from those salts, [alpha] -hydroxy acids such as glycolic acid, lactic acid, malic acid, citric acid, salicylic acid and their derivatives and salts thereof.   The composition according to claim 1, wherein the medicinal agent is an anti-inflammatory agent.   Anti-inflammatory agents are glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene and their derivatives and their salts, ε-aminocaproic acid, zinc oxide, diclofenac sodium, aloe extract The composition according to claim 8, wherein the composition is selected from the group consisting of salvia extract, arnica extract, chamomile extract, birch extract, hypericum extract, eucalyptus extract and mukuroji extract.   The composition according to claim 1, wherein the medicinal agent is a tyrosinase activity inhibitor.   The tyrosinase activity inhibitor is cysteine and its derivatives and salts thereof, Sempukuka extract, Caiket extract, Sampens extract, Sakuhakuhi extract, Toki extract, Ibukitorano extract, Clara extract, Hawthorn extract, Shirayuri extract 11. The composition according to claim 10, wherein the composition is selected from hop extract, Neubara extract and Yokuinin extract.   The composition according to claim 1, wherein the medicinal agent is a humectant.   The composition according to claim 12, wherein the humectant is a mucopolysaccharide and / or a protein.   The composition 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.   The composition according to claim 13, wherein the protein is selected from collagen, elastin, keratin and derivatives thereof, and salts thereof.   16. The composition according to any one of claims 1 to 15, which is an external preparation for skin.   The composition according to any one of claims 1 to 15, which is a cosmetic. 16. The composition according to any one of claims 1 to 15, which is a topical medicine.