JP2003014739A - Screening method of skin swell improvement agent, and skin swell improvement agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for screening a skin swell improvement agent easily, safely, and reliably, and to provide the skin swell improvement agent. SOLUTION: In the screening method of skin swell improvement agents, a reagent to be tested is added to a collagen gel containing corium fibroblast and the amount of water oozed out of the gel is measured after effective time, thus judging the skin swell improvement effect of the reagent to be tested. The skin swell improvement agent includes the extract of plants belonging to Bupleurum, that of plants belong to Coix, that of plants belong to Zea, and one type or two types selected from milk spirit extracts.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for screening a skin swelling improving agent, and a skin swelling improving agent. More specifically, the present invention relates to a screening method capable of selecting a skin swelling improving agent easily, safely and reliably using a collagen gel containing dermal fibroblasts as a dermis model, and a skin swelling improving agent.

[0002]

2. Description of the Related Art Skin is a stratum corneum that extends inward from the outermost layer.
It is composed of the epidermal layer, the basement membrane, and the dermal layer in this order.
The dermis layer consists of dermal fibroblasts and collagen fibers surrounding them, and collagen fibers are synthesized by dermal fibroblasts. Abnormal accumulation of water in the spaces between the collagen fibers is the swelling mode. Swelling occurs when a large amount of water in the blood moves into tissues, or when the perfusion of water into blood vessels or lymph vessels is blocked.
Swelling is a symptom caused by poor factors such as posture, heart, kidneys, nutritional status, etc., and cannot be evaluated by a single physiological index.

Conventionally, as a method for determining the degree of swelling, for example, when swelling is found in a foot (calf etc.), a method of measuring the circumference of the calf, a method of putting the entire foot in water and measuring the volume thereof are used. Has been. Although these measuring methods are actually tested in humans, they are time-consuming and labor-intensive. Furthermore, the selection of a drug for improving such swelling has not yet been found to be a sufficiently satisfactory method.

On the other hand, a method for in vitro testing of swelling of human skin has been studied. For example, fibroblasts in the stratum corneum of the skin are monolayer-cultured, to which a test substance is added, and ion permeation thereof is conducted. A method for evaluating the degree of improvement in skin swelling of a test substance based on changes in sex has been reported. Although this method is simple, it only looks at one aspect of the cause of swelling, and it cannot be said to be an evaluation method that fully reflects the actual conditions of swelling.

Under these circumstances, there has been a demand for an in vitro swelling evaluation method and a selection method for a swelling improving agent, which are in accordance with the actual conditions of swelling.

[0006]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and an object thereof is to provide a method for screening a skin swelling improving agent in a simple, safe and reliable manner, and a skin swelling improving agent. And

[0007]

[Means for Solving the Problems] As described above, since it is a swelling condition that water is stored in the gaps between the collagen fibers of the dermis layer, if the stored water is exuded and excreted into the blood vessel, The swelling is resolved. The present inventors have used the collagen containing dermal fibroblasts as a model of the dermis, to which a test reagent is added, and to measure the amount of the liquid exuded from the gel after culturing to solve the above problems. They have found that they can be solved and have completed the present invention.

[0008] That is, the present invention is a method for screening a skin swelling improving agent, which comprises adding a test reagent to a collagen gel containing dermal fibroblasts, and after elapse of an effective time, the amount of water exuded from the gel. The present invention relates to a method for screening a skin swelling improving agent, which comprises determining the skin swelling improving effect of the test reagent by measuring

The present invention also relates to the genus Bupleuru.
m), an extract of a plant belonging to the genus (Coix), an extract of a plant belonging to the genus (Zea), and one or more selected from whey extract. And the above-mentioned skin swelling improving agent.

The present invention also relates to the genus Bupleuru.
The above-mentioned skin swelling improving agent, wherein the active ingredient of the plant extract belonging to m) is saikosaponin and / or psychogenin.

The present invention further relates to the above-mentioned swelling-improving agent, wherein the extract of the plant belonging to the genus Coix is a coix seed extract.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below.

The collagen gel containing dermal fibroblasts used in the present invention can be prepared by a known method. Specifically, for example, after adding a suspension of dermal fibroblasts to a collagen solution in a container such as a culture plate, culturing at 37 ° C. for about 18 to 72 hours in a culture vessel. It can be made by
It is not limited to this. As the container, a culture plate having 6 holes, 12 holes, 24 holes or the like, a petri dish or the like is preferably used.

The collagen used is not particularly limited as long as it is animal-derived collagen, but mammalian-derived collagen is preferable, and collagen derived from human, mouse, rat, rabbit, guinea pig, bovine, etc. is more preferable. In particular, human-derived collagens of type I, type III, and type IV are preferable, and type IV collagen is particularly preferable.
These collagens may be collected from a tissue by a known method and used, or “I-AC” (manufactured by Koken Co., Ltd.) commercially available as a collagen solution may be used.

The dermal fibroblasts are not particularly limited as long as they are derived from animals, as described above, but those derived from mammals are preferable, and those derived from humans are particularly preferable.

The test reagent added to the collagen gel is not particularly limited, and compounds, chemical substances, animal and plant extracts and the like are widely applied.

In the screening method of the present invention, a test reagent to be screened is added to a collagen gel, and after elapse of an effective time, the amount of water exuded from the gel is measured.

The above-mentioned effective time means that the added test reagent acts on the dermal fibroblasts and collagen in the collagen gel to exert the collagen contracting action of the test reagent to promote the exudation of water from the gel. It means a sufficient time, and generally about 18 to 48 hours is preferable. After adding the test reagent to the collagen gel, it is cultured in a medium so that the cell activity can be maintained. The medium used is not particularly limited, and includes, for example, MEM medium, DMEM medium, PBS.
Buffers and the like can be mentioned, but especially MEM supplemented with serum
A medium is preferably used.

The degree of improvement in swelling of the test reagent is evaluated by the amount of water exuding from the gel after the elapse of the effective time. In the present invention,
Collagen gel containing dermal fibroblasts is regarded as a mesenchymal model of the dermis layer, and due to the action of the test reagent added to it, the amount of water stored in this gel is exuded to the outside of the gel. Thus, it is possible to evaluate that the swelling improvement degree of the test reagent is high, and thus it is possible to appropriately screen as a swelling improving agent.

As a swelling improving agent selected by such a screening method, the genus Bupleuru
m), an extract of a plant belonging to the genus (Coix), an extract of a plant belonging to the genus (Zea), and one or more selected from whey extract. The swelling improving agent according to the present invention is included.

Examples of extracts of plants belonging to the genus Bupleurum include, for example, Mishima Psycho [Mishima Shibahu (Japanese Pharmacopoeia 13th revision name: B. falcatum Linn
e)], also known as B. chinese DC., also known as B. chinese DC., and B. scorzonerifolium Will, also known as B. chinese DC.
d.), Membrane edge Saiko (B. marginatum Wall. ex DC.), Chobakushibahu (B. komarovianum Lincz.), Ohba Saiko (B. longi)
radiatum Turcz.), Singaung Koan (B. sibiricum Vest),
B. longicaule Wall. Ex DC., Koshiba (B. longicaule Wall. Ex DC.)
tenue Buch.-Ham ex D.Don), which is also called by the name of Saibahu, also known as B. aureum Fisch.
Extracts such as mulutinerve Dc.) can be mentioned.

The site used in the above plant is not particularly limited as long as it is a site capable of containing saikosaponin or psychogenin. For example, in the case of Mishima Psycho, it is desirable to use a root portion known to contain Psychosaponin and Psychogenin.

As these plants, not only natural plants but also artificially cultured plants may be used. As the artificially cultured plant body, for example, saikosaponin, callus derived by culturing a specific part of the plant body in order to improve the production efficiency of psychogenin, or an organ of a specific part by further differentiating the callus. Cultivated plants can be used.

Further, a genetically engineered method, for example, a transgenic strain or a cell fusion strain produced for the purpose of producing a large amount of saikosaponin or psychogenin may be used.

Regarding Mishima Psycho, which is preferably selected as a plant producing saikosaponin and / or psychogenin, protoplasts to be used for plant culture are nicotinic acid, pyridoxine hydrochloride, calcium D-pantothenate, p-aminobenzoic acid, choline chloride. , Ascorbic acid, vitamin A, vitamin D ₃ , vitamin B ₁₂ ,
It is preferable to culture in a culture medium containing at least one vitamin or organic acid selected from sodium pyruvate, citric acid, sodium malate, fumaric acid and casamino acid (see JP-A-2-245180).

In addition, during the organ culture of the root of the flesh-breasted peach, the saccharide components (sucrose, glucose, fructose) of the organ culture medium are increased until the number of lateral roots does not substantially increase even when the organ culture is continued. ,etc)
It is preferable to limit the concentration to less than 2.0% by mass with respect to the entire medium and to culture it, since the production efficiency of saikosaponin in organ culture can be improved.
23069). Further, to the culture medium, add a phenol derivative such as coumarin, m-hydroxybenzoic acid, o-hydroxyphenylacetic acid, p-hydroxyphenylacetic acid, o-coumarinic acid, chlorogenic acid, phloroglucinol, and umbelliferone. Also, it is preferable in that the production efficiency of saikosaponin in organ culture can be improved (see JP-A-5-184379).

When a gene capable of improving the production of saikosaponin (for example, a saikosaponin synthetic gene) is introduced into a plant belonging to the genus Mishimasai, DNA containing the gene code of such a gene is targeted for transfection. It is preferable to coexist with a protoplast of a plant belonging to the genus, to give an electric pulse or to add a cell fusion agent, from the viewpoint that a desired gene transfer can be efficiently realized (see JP-A-6-90771). ).

An extract of a plant belonging to the genus Mishima genus can be obtained by a conventional method. For example, the plant can be obtained by immersing or heating under reflux with an extraction solvent, filtering and concentrating. The extract referred to here includes not only the case where it is derived from a crushed plant, but also the case where it is derived from a medium in which plant tissue culture such as organ culture is performed as described above. Any solvent can be used as the extraction solvent as long as it is a solvent usually used for extraction. For example, water such as purified water; monohydric lower alcohols such as methanol and ethanol sugar; oleyl alcohol, stearyl alcohol, octyldodecanol. Monohydric higher alcohols such as ethylene glycol, propylene glycol, glycerin,
Polyols of 1,3-butylene glycol sugar; ketones such as acetone; esters such as acetic acid ethyl ester;
Hydrocarbon-based solvents such as hexane, chloroform, benzene and the like can be mentioned. These can be used alone or in combination. Of these, water, ethanol, glycerin, and 1,3-butylene glycol are preferably used alone or as a mixture of two or more thereof, because they can be widely applied to living organisms. The extract obtained by extraction with the above solvent is used as it is, or the concentrated extract is adsorbed by an adsorption method, for example, one obtained by removing impurities using an ion exchange resin, or a column of a porous polymer (for example, Amberlite XAD-2). It is possible to use a product obtained by eluting with methanol or ethanol after the reaction and concentrating. Further, a partitioning method, for example, an extract extracted with water / ethyl acetate or the like is also used.

In addition, the swelling improving agent of the present invention may contain, as an active ingredient, saikosaponin and / or saikogenin known to be contained in the above extract.

Psychosaponin is a dried root of Mishima Psycho and is one of the important Chinese herb raw materials that has been used as a crude drug for antipyretic, detoxifying, analgesic, tonic and anti-inflammatory since ancient times. Psycho) "is known as the main pharmacological component. This saikosaponin is an oleanane-type triterpenoid saponin, and has been a, c, d,
The structure has been determined by isolating 13 kinds such as b1 and b2. The swelling improving agent of the present invention may contain saikosaponin isolated by these commonly known methods.

The swelling improving agent of the present invention may contain saikosaponin prepared by means of mass acquisition. The saikosaponin is contained in the natural root of Mishima saiko only in an amount of about 0.5 to 1.5% by mass.

As an example of this means for obtaining a large amount, the above-mentioned extract containing saikosaponin is once adsorbed on an adsorbent and various means are applied to the adsorbent to obtain a large amount of saikosaponin of a desired type. There is a method. Specifically, the extract is brought into contact with an adsorbent to adsorb saikosaponin to the adsorbent, and the components of the extract other than saikosaponin are removed from the adsorbent (adsorption step). The adsorbed saikosaponin was eluted, and purified natural saikosaponin (double bond 13
Psychosaponin that exists as it is in natural products represented by only rank. Psychosaponin a, Psychosaponin c, Psychosaponin d) can be obtained.

After the yield of the above-mentioned extract on the adsorbent, the iron (II) was added to the saikosaponin adsorbed on the adsorbent.
I) contacting ions [eg iron chloride (FeCl ₃ )
A solution of iron (III) ions, such as a solution of iron (III) salt such as, for example, directly in contact with this natural type saikosaponin], and a saikosaponin having a diene structure (for example, double bonds at the 13- and 14-positions) Type saikosaponin, saikosaponin b1, saikosaponin h, saikosaponin b2,
Etc.) can be obtained.

The saikosaponin having a diene structure obtained by converting the natural saikosaponin a is saikosaponin b1. Similarly, saikosaponin c corresponds to saikosaponin h, and saikosaponin d corresponds to saikosaponin d. For example, Psychosaponin b2 corresponds.

Examples of the adsorbent used in these steps include activated carbon, styrene-divinylbenzene type synthetic adsorbent, acrylic synthetic adsorbent and the like. In addition, a synthetic adsorbent made of a material in which silica gel and a hydrophobic group are combined, a polyamide gel, a modified dextran gel and the like can be mentioned.

The desired type of saikosaponin adsorbed on these adsorbents is eluted with a suitable eluent, and purified by high performance liquid chromatography or the like, if necessary, to obtain the desired saikosaponin. Saponin is available.

Psychosaponins other than Psychosaponin whose production method is exemplified above, such as Psychosaponin e,
Saikosaponin f, saikosaponin g and the like can also be produced by a generally known method.

The swelling improving agent of the present invention includes these saikosaponin a, saikosaponin b1, and saikosaponin b.
2. Any of the saikosaponins c, saikosaponin c, saikosaponin d, saikosaponin e, saikosaponin f, saikosaponin g, and saikosaponin h can be blended.

The swelling improving agent of the present invention may contain genin component of the above-mentioned saikosaponin, that is, psychogenin which is a non-carbohydrate portion of saikosaponin. In particular,
Psychogenin A which is the genin part of Psychosaponin b1, Psycogenin C which is the genin part of Psychosaponin h, Psychogenin D which is the genin part of Psychosaponin b2, Psycogenin E which is the genin part of Psychosaponin c, and the genin part of Psychosaponin a And Psychogenin G of Psychosaponin d. These psychogenins can be obtained by hydrolyzing each of the corresponding psychosaponins by a sugar elimination reaction under acidic conditions with hydrochloric acid, sulfuric acid or the like.

The compounding amount of the extract of the plant belonging to the genus Bupleurum is 0.0005 to 0.1% by mass in the swelling improving agent of the present invention in terms of the amounts of saikosaponin and psychogenin which are the active ingredients. It is preferably about 0.001 to 0.05% by mass.

The plant belonging to the genus Coix can be used without particular limitation as long as it is an extract of a plant belonging to the same genus.
"Eed)", the shell grains of coix, which is a homologous plant, are preferably used. The extract of Yokuinin can be carried out in the same manner as the above-mentioned plant of the genus Lorikeet.

The amount of the extract of the plant belonging to the genus Coix which is contained in the swelling improving agent of the present invention is preferably about 0.0001 to 1.0% by mass, particularly 0.0005, in terms of solid content. Is about 0.5% by mass.

As a plant belonging to the genus (Zea), corn (Zea mays) is preferably used. The site to be used is not particularly limited,
Roots are preferably used. This extract of corn can be carried out in the same manner as the above-mentioned extraction of the plant of the genus Mishima.

The amount of the extract of plants belonging to the genus (Zea) is preferably about 0.00001 to 0.001% by mass in terms of solid content in the swelling improving agent of the present invention, and particularly 0.0001. Is about 0.001% by mass.

The milk semen extract used in the present invention can be obtained by a conventional method. Specifically, the following method may be mentioned. That is, after centrifuging healthy bovine milk,
Skim milk with an extremely low fat content is collected from the lower layer, and an acid such as an organic acid or an inorganic acid is added thereto to adjust the pH to about 4.5 to 5.0. This precipitates casein. The precipitated casein was taken out and further centrifuged,
The supernatant can be neutralized with an alkaline solution such as sodium hydroxide solution, and then concentrated under reduced pressure to remove ethanol to obtain a milk semen extract. However, the method is limited to this method. Of course not what is done.

The amount of the above-mentioned milk semen extract is preferably about 0.0001 to 1.0% by mass, and more preferably 0.0005 to 0.8% by mass, in terms of solid content, in the swelling improving agent of the present invention.
It is a degree.

The swelling improving agent of the present invention contains, in addition to the above-mentioned essential components, components that are usually used in external preparations for skin such as cosmetics and pharmaceuticals, such as whitening agents, moisturizing agents, antioxidants, oily ingredients, and ultraviolet absorbers , Surface active agents, thickeners, alcohols, powder components, coloring materials, aqueous components, various skin nutrients and the like can be appropriately blended as necessary.

In addition, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, various crude drugs , Tocopherol acetate,
Drugs such as glycyrrhizinic acid and its derivatives or salts thereof, other whitening agents such as vitamin C, phosphomagnesium ascorbate, ascorbate glucoside, arbutin and kojic acid, and sugars such as glucose, fructose, mannose, sucrose and trehalose. It can be blended appropriately.

The skin swelling improving agent according to the present invention can be widely applied to cosmetics, pharmaceutical parts and the like applied to the outer skin, particularly preferably to cosmetics, and its formulation is an aqueous solution type,
A wide range of dosage forms such as solubilization type, emulsification type, powder type, oil liquid type, ointment type, aerosol type, water-oil two-layer type, water-oil-powder three-layer type can be adopted.

That is, for basic cosmetics, a face wash,
It is widely applicable to various forms such as lotions, emulsions, creams, gels, essences (packs), masks and the like. Further, makeup cosmetics can be widely applied to a form such as foundation, and toiletry products can be widely applied to forms such as body soap and soap. Furthermore, quasi-drugs can be widely applied to various forms such as ointments. The forms that the skin swelling improving agent of the present invention can take are not limited to these dosage forms and forms.

[0051]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited thereto. The blending amount is% by mass.

(Examples 1 to 3) A MEM medium containing 4 times the concentration of fetal calf serum, a type IV collagen solution and a suspension of human dermal cells were mixed at a low temperature to give a final concentration of fetal calf serum of 0.1.
%, Collagen concentration 0.1%, cells 1 × 10 ⁵ / mL
1 mL was wound on a 12-well plate. 37
After the gel was solidified by culturing at 2 ° C. for 2 hours, as shown in Table 1, a PBS solution containing a final concentration of 0.0001% by mass to 0.1% by mass of saikosaponin was added. As a control, only a PBS solution (without psychosaponin) was added. Keep the temperature at 37 ° C and continue culturing,
After 24 hours, the exudate around the gel was carefully collected, the exudate amount was measured, and the exudate amount in each case when the control was 100 was calculated. The results are shown in Table 1.

[0053]

[Table 1]

As is clear from the results shown in Table 1, it was shown that the addition of saikosaponin promotes liquid exudation from the collagen gel. From this, it was confirmed that saikosaponin has a swelling improving effect.

(Examples 4 to 7) A MEM medium containing 4 times the concentration of fetal bovine serum, a type IV collagen solution and a suspension of human dermal cells were mixed at a low temperature to give a final concentration of fetal calf serum of 0.1.
%, Collagen concentration 0.1%, cells 1 × 10 ⁵ / mL
1 mL was wound on a 12-well plate. 37
After the gel was solidified by culturing at 2 ° C. for 2 hours, as shown in Table 2, a PBS solution containing a final concentration of 0.0006% by mass to 0.6% by mass of milk semen was added. As a control, only the PBS solution (without milk semen) was added. 37 ° C
The culture was continued while maintaining the temperature of 24 hours, and after 24 hours, the exudate around the gel was carefully collected, the exudate amount was measured, and the exudate amount in each case when the control was 100 was calculated. . The results are shown in Table 2.

[0056]

[Table 2]

As is clear from the results shown in Table 2, the addition of the milk semen extract was shown to promote the exudation of liquid from the collagen gel. From this, it was confirmed that the milk semen extract has a swelling improving effect.

(Examples 8 to 10) A MEM medium containing 4 times the concentration of fetal calf serum, a type IV collagen solution and a suspension of human dermal cells were mixed at a low temperature to give a final concentration of fetal calf serum of 0.
1%, collagen concentration 0.1%, cells 1 × 10 ⁵ / m
L solution was made and 1 mL was wound on a 12-well plate. Three
After culturing at 7 ° C. for 2 hours to solidify the gel, as shown in Table 3, a 50% ethanol solution containing a final concentration of 0.0001% by mass to 0.1% by mass of yoquinin was added. As a control, only a 50% ethanol solution (without Yokuinin) was added. The culture was continued while maintaining the temperature at 37 ° C., and after 24 hours, the exudate around the gel was carefully collected, the exudate volume was measured, and the control was set to 1
The amount of exudate in each case when it was set to 00 was calculated. The results are shown in Table 3.

[0059]

[Table 3]

As is clear from the results shown in Table 3, it was shown that the addition of Yokuinin extract promotes liquid exudation from the collagen gel. From this, it was confirmed that Yokuinin has a swelling improving effect.

(Examples 11 to 13) 4 containing fetal bovine serum
Double-concentration MEM medium, type IV collagen solution, and human dermal cell suspension were mixed at low temperature to give a final concentration of fetal bovine serum 0.1%, collagen concentration 0.1%, cells 1 × 10 ⁵
/ ML of solution was made and 1 mL was wound on a 12-well plate. After culturing at 37 ° C. for 2 hours to solidify the gel, as shown in Table 4, the final concentration was 0.00001% by mass to 0.00%.
A PBS solution containing 1% by weight of corn extract was added. As a control, only the PBS solution (without corn) was added. The culture was continued while maintaining the temperature at 37 ° C., and after 24 hours, the exudate around the gel was carefully collected, the exudate volume was measured, and the control was set to 1
The amount of exudate in each case when it was set to 00 was calculated. The results are shown in Table 4.

[0062]

[Table 4]

As is clear from the results shown in Table 4, addition of the corn extract was shown to promote the exudation of liquid from the collagen gel. From this, it was confirmed that the corn extract has a swelling improving effect.

[0064]

INDUSTRIAL APPLICABILITY As described in detail above, according to the present invention, a simple in vitro test method can be performed in an environment close to physiological conditions.
It is possible to evaluate the effect of eliminating swelling of the skin, which allows the swelling improving agent to be screened easily and accurately. By this method, it was found that the extract of plants belonging to the genus Mishima (especially saikosaponin), the corn extract, the extract of plants belonging to the genus Juzudama (especially Yokuinin extract), and the dairy extract have a swelling improving effect. It was

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) G01N 33/48 G01N 33/48 N (72) Inventor Rikako Furuya 2-2-Sayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 1 Incorporated Shiseido Research Center (Shin-Yokohama) (72) Inventor Mitsuhiro Denda 2-12-1, Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa Prefecture Incorporated Shiseido Research Center (Hakkei Kanazawa) (72) Inventor Toru Tsuchiya Kanagawa 2-12-1, Fukuura, Kanazawa-ku, Yokohama-shi F-term in Shiseido Research Center (Hakkei Kanazawa) (reference) 2G045 AA40 BB20 CB01 CB09 DB22 4C088 AA01 AA02 AB40 AB77 AB78 AC04 AC11 BA13 ZA89

Claims (4)

[Claims] 1. A method for screening a skin swelling improving agent, which comprises adding a test reagent to a collagen gel containing dermal fibroblasts, and measuring the amount of water exuded from the gel after a lapse of effective time. The method for screening a skin swelling improving agent is characterized by determining the skin swelling improving effect of the test reagent. 2. An extract of a plant belonging to the genus Bupleurum, an extract of a plant belonging to the genus Coix, an extract of a plant belonging to the genus Zea,
And an agent for improving skin swelling, which comprises one or more selected from milk semen extracts. 3. The skin swelling improving agent according to claim 2, wherein the active ingredient of the extract of the plant belonging to the genus Bupleurum is saikosaponin and / or psychogenin. 4. The skin swelling improving agent according to claim 2, wherein the extract of a plant belonging to the genus Coix is a coix seed extract.