JPH11292785A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a preparation for external use for skin that has the action to inhibit the damage of dermal fibroblast cells by ultraviolet rays; prevents the formation of peroxy lipid caused by the occurrence of active oxygen in the skin and is effective for the prevention and improvement of the symptoms such as occurrence of wrinkles or deterioration in skin elasticity; and has the effect for preventing or improving the formation of peroxide lipids caused by the occurrence of active oxygen in the skin, to prevent and improve skin inflammation and roughening. SOLUTION: One or more kinds selected from an extract from Agaricus mushroom fruits and the filtrate of the mycelium culture are combined with an active oxygen scavenger and they are formulated to a preparation for external use for skin. As an active oxygen scavenger, is preferably used an extract from plants having the action to scavenge active oxygen, for example, Hamamelis, Quercus, Aesculus, Sanguisorba, Paeonia, Ginkgo bibloba L., Betulaceae tree, parsley (Petroselium saticum or the like); additionally, carotenoid, flavonoid, tannin, superoxide dismutase, gallic acid and its salts or derivatives, hydroquinone, thioredoxin, thioredoxin reductase and the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention is excellent in the action of preventing rough skin and aging of the skin, has the action of protecting the dermal fibroblasts from damage by ultraviolet rays, and prevents the occurrence of wrinkles and the reduction of skin elasticity. The present invention relates to an external preparation for skin which is effective for improvement and has an effect of preventing or improving the production of lipid peroxide due to the generation of active oxygen in the skin, the inflammation of the skin and the rough skin. More specifically, one or more selected from Agaricus blazei Murill mycelium extract and Agaricus blazei Murill mycelium culture filtrate (hereinafter abbreviated as Agaricus mushroom extract), and active oxygen scavenging The present invention relates to an external preparation for skin, which is used in combination with an agent.

[0002]

2. Description of the Related Art Skin aging is roughly classified into photoaging caused by ultraviolet rays and natural aging caused by functional deterioration and atrophic change due to functional deterioration due to aging. Therefore, it contains a skin external preparation for eliminating active oxygen species in cells generated by ultraviolet rays and preventing photoaging, and a compound having a skin cell activating effect for the purpose of improving skin cell function deterioration due to aging. Skin external preparations and the like have already been disclosed. However, these aging phenomena rarely appear independently of each other, and often appear when two agings overlap.

[0003]

Therefore, the present invention has an excellent action of preventing skin roughness and aging, and has an action of preventing damage to dermal fibroblasts by ultraviolet rays,
It is effective in preventing or improving symptoms such as wrinkles and decreased skin elasticity, and has the effect of preventing or improving lipid peroxide generation due to active oxygen generation in the skin, skin inflammation and skin roughness. The purpose was to obtain a skin external preparation.

[0004]

Means for Solving the Problems The present inventors have found that a high dermal fibroblast activating action can be obtained in Agaricus mushroom extract (Japanese Patent Application No. 9-31277).
1). This time, by combining this Agaricus mushroom extract with an active oxygen scavenger in an external preparation for skin, it has an excellent anti-skin roughening and antiaging effect, and has an action to protect dermal fibroblasts from damage by ultraviolet rays. It is effective in preventing or improving symptoms such as generation of wrinkles and decreased skin elasticity, and has the effect of preventing or improving the production of lipid peroxide due to the generation of active oxygen in the skin, skin inflammation and rough skin. They have found that they can demonstrate their benefits and have solved the above-mentioned problems.

[0005]

Embodiments of the present invention will be described.

The agaricus mushroom ( Agaricu) used in the present invention
s blazei Murill) is a kind of agaric genus of the basidiomycete agaricaceae agaricaceae, and is also referred to as agaricus or agaricus, and is deposited with the National Institute of Advanced Industrial Science and Technology, National Institute of Bioscience and Human Technology, and deposited under No. 4731.

As a method of cultivating the Agaricus mushroom strain to obtain the Agaricus mushroom mycelium, any of a solid culture method and a liquid culture method usually used for cultivation of basidiomycetes may be employed. It is preferably used from the viewpoint of sex. The medium used for cultivation of Agaricus mushrooms may be any medium as long as it contains various nutrients necessary for the growth of the bacterium, and may be an ordinary medium formulation. That is, as the carbon source, any carbon source that can be assimilated, such as glucose, sucrose, maltose, and starch, can be used. Nitrogen sources include, for example, ammonium sulfate, ammonium nitrate, and urea. Natural complex nutrients include, for example, potato extract, carrot extract, malt extract, peptone, koji extract,
Yeast extract, yeast powder, etc. can be used, and other trace elements such as inorganic salts and vitamins necessary for growth are appropriately added and used.

The cultivation is usually performed under aerobic conditions, for example, a shaking culture method or an aeration stirring culture method. The stirring during the culture may be performed by reciprocal shaking or rotary shaking for several minutes every 24 hours, or may be performed by continuous shaking. The culture temperature is 15 ° C to 40 ° C, preferably around 20 ° C to 30 ° C. The pH of the medium is preferably in the range of 3.0 to 9.0.
The growth is good at 5 to 7.0. It is preferable not to illuminate during culturing, but illuminating for about 11 to 14 hours per day is possible.

[0009] The culturing period varies depending on the culturing conditions such as the physical environment and the composition of the medium. The culturing period may be a period in which the growth of mycelium is sufficiently recognized, and is usually 2 to 120 days, particularly preferably 5 to 90 days. The best time to produce the mycelium is good.

After completion of the culture, the culture solution is centrifuged or filtered to separate the mycelium from the culture filtrate. Centrifugation can be performed by a centrifugal operation giving a gravitational acceleration of 100 to 5000 G, preferably 800 to 3000 G.
The filtration is performed using a membrane filter of 3.5 to 200 mesh, particularly preferably 4 to 16 mesh.

When an extract is obtained from the mycelium of Agaricus mushroom, the raw mycelium obtained from the culture solution cultured as described above can be used as it is or after drying. As the solvent for extraction from the mycelium, a polar solvent is preferably used. For example, water, alcohols such as ethanol, methanol, isopropanol, isobutanol, n-hexanol, methylamyl alcohol, 2-ethylbutanol, n-octyl alcohol, glycerin, ethylene glycol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether Solvent or polyhydric alcohol such as propylene glycol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, triethylene glycol, 1,3-butylene glycol, hexylene glycol or derivatives thereof, or two or more solvents Can be used. Further, an inorganic salt, a surfactant and the like may be added to a polar solvent. Among these polar solvents, ethanol,
One solvent selected from methanol, 1,3-butylene glycol, and water, or a mixed solvent of two or more solvents, and a solvent obtained by adding an inorganic salt and a surfactant to these solvents are preferably used.

[0012] Further, as an extraction method, a method of extraction by impregnation at room temperature while being cooled or heated, a method of extraction using a distillation method such as steam distillation, and a method of directly pressing raw Agaricus mushroom mycelium. Examples of the squeezing method to obtain the extract,
These methods are used alone or in combination of two or more.

The ratio of Agaricus mushroom mycelium to the solvent at the time of extraction is not particularly limited, but the solvent is 0.5 to 1000 times the weight of Agaricus mushroom mycelium 1, especially in terms of extraction operation and efficiency. Is preferably 0.5 to 100 times by weight. The extraction temperature is conveniently in the range of 5 ° C. to the boiling point of the solvent at normal pressure, and the extraction time varies depending on the extraction temperature and the like, but is preferably in the range of 2 hours to 2 weeks.

The extract of Agaricus mushroom mycelium thus obtained can be used as it is, but it can be used for fractionation, deodorization, decolorization, concentration, etc. within a range that does not impair the effects of the present invention. A purification operation may be added for use. These extracts, their purified products, and fractionated products can be dried by removing the solvent therefrom, and can be further dissolved or suspended in a solvent such as purified water or an emulsion. It can be added to a skin external preparation in a form.

On the other hand, the filtered mycelium culture filtrate can be directly blended with an external preparation for skin. However, the culture filtrate is subjected to purification, such as fractionation, deodorization, decolorization, and concentration, within a range that does not impair the effects of the present invention. It can also be used with additional operations. These culture filtrates, their fractions, and purified products can be dried to remove the solvent from them, and can be further dried or solubilized or suspended in a solvent such as purified water, or an emulsion. It can be added to a skin external preparation in a form.

The amount of the Agaricus mushroom extract to be added to the external preparation for skin is desirably in a concentration range of 0.0001 to 5% by weight in view of its effect, odor and color tone when added.

The active oxygen scavenger used in the present invention is not particularly limited as long as it can be used as an external preparation for skin. For example, plant extracts, carotenoids, flavonoids, tannins having an active oxygen scavenging action , Superoxide dismutase, hydroquinone and salts or derivatives thereof, thioredoxin, thioredoxin reductase, and the like.

The plant extracts used in the present invention include:
It preferably contains carotenoids, flavonoids, and tannins. For example, Hamamelis japonica
Sieb.et Zucc., Hamamelis obtsusata Makino, Hama
melis japonica Sieb.et Zucc.var. obtsusata Matsum.
, Hamamelis virginiana L., Hamamelis mollis Oli
v.), Quercus serrata, Horse chestnut, Scarlet genus, Ginseng , Ginkgo ( Ginkgo bibloba L.),
Birch plant, parsley ( Petroselium saticum , Petro
selium sativm Hoffm., Petroselium crispum Nyman,
Petroselium hortense Hoffm., Petroselium crispum
(Mill.) Nym.ex AW Hill, Apium petroselium
L.) and the like.

The Hamamelis ( Ha) used in the present invention
mamelis japonica Sieb.et Zucc., Hamamelis obtsusat
a Makino, Hamamelis japonica Sieb.et Zucc.var.obt
susata Matsum., Hamamelis virginiana L., Hamamel
is mollis Oliv.) is a deciduous tree distributed in slightly humid forests in eastern North America, Canada and Mexico. The dried leaves are called hamamelis tea, and the bark has been used in the production of hamamelis water as a laxative. In the present invention, the extraction site for obtaining the extract of Hamamelis is not particularly limited, and includes bark and its mucus, leaves, flowers, branches, roots, etc. Among them, one or more selected from leaves and bark It is preferable to use extracts from two or more sites.

The Quercus plant used in the present invention is a plant belonging to the family Fagaceae . In the present invention, the plant is not particularly limited as long as it is a plant of the genus Quercus, and for example, Quercus serrat ( Quercus serrat )
a Thunb., Quercus grandulifera Blume, Quercus se
rrata Murray), Quercus serrata ( Quercus gros )
seserrata Blume, Quercus crispula Blume, Quercus
mongolica Fisch.var.grosseserata (Blume) Rehd.e
t Wils.), Quercus ( Quercus acutissima Carruth.),
Oriental oak (Watakunugi, Watamaki, Okunugi, Kurigashiwa) (Quercus variabilis Blume), oak (Kashiwagi, Mochigashiwa) (Quercus dentata Thunb.), Quercus Aliena (Quercus aliena Blume), phillyraeoides (Imamegashi, Umamegashi) (Quercus phillyraeoides A. Gra
y), Shirakashi (black oak) ( Quercusmyrsinaefolia Bl
ume, Cyclobalanopsis myrsinaefolia (Blume) Oers
t.), Arakashi ( Quercus glauca Thunb., Cyclobalan
opsis glauca (Thunb.) Oerst. ), Quercus Sessilifolia (Quer
cus paucidentata Franch., Quercus salicina Blume
, Cyclobalanopsis paucidentata Kudo et Masam., Qu
ercus sessilifolia Blume, Cyclobalanopsis sessilif
olia Blume) and Vulture ( Quercus stenophylla Ma)
kino, Quercus salicina Blume, Cyclobalanopsis sa
licina (Blume) Oerst.), Yokomegashi (Shimagashi) (Q
uercus glauca Thunb. var. fasciata Blume) and Hirugashi ( Quercus glauca Thunb. var. lacera Matsu)
m.), Red oak (Oogasi, Oobagashi) ( Quercus ac
uta Thunb., Cyclobalanopsis acuta (Thunb.) Oers
t.), yew (Yew, yew) ( Quercus gilv
a Blume, Cyclobalanopsis gilva (Blume) Oerst.),
White oak ( Quercus alba L.), Swamp white oak ( Quercus bicolor Willd.), Turkey oak (Italian oak) ( Quercus cerris L.), Mall oak (Canyon live oak) ( Quercus chrysole
pis Liebm.), Ishiguri ( Quercus cornea Lour., Lythocar)
pus cornea (Lour.) Rehd.), Shinoak ( Quercus gamb )
elii Nutt.), Ensina ( Quercus agrifolia Nee),
Amory Oak ( Quercus emoryi Torr.), Mesa Oak ( Quercus engelmannii Greene), Oregon White Oak ( Quercusgarryana Dougl.), California Black Oak ( Quercus kellogi Newsb.), California White Oak ( Quercus lobata Nee), Wavy Leaf Oak ( Quercus undulata Torr) .), Cork oak ( Quercus lucombeana Sweet, Quercus suber L.), Home or Holy oak ( Quercus ilex L.), Okinawan Wolverine oak ( Quercus miyagii Koidz., Cyclo
balanopsis miyagii (Koidz.) Kudo et Masamune), Mongolinara ( Quercus mongolica Fisch.v)
ar. mongolica ), chestnut oak ( Quercus prinus)
L.), Common Oak (English Oak) ( Querc
us robur L.), Takayama lime ( Quercus semicarpifolia S)
m.) and the like. Among these plants of the genus Quercus, it is preferable to use one or two kinds of plants selected from Quercus serrata (oak) and Mizunara (oakara) from the viewpoint of the effects of the present invention. Further, the extraction site for obtaining the extract of Quercus serrata is not particularly limited, and the bark and its mucus, fruit,
Examples thereof include seeds, flowers, branches, leaves, and roots. Among them, extracts from one or more sites selected from leaves, bark, branches, and roots are most preferable from the viewpoint of the effects of the present invention. .

The plant of the genus Aesculus used in the present invention is a plant belonging to the family Aesculus ( Hippocastanaceae ). Examples of a horse chestnut plant are not particularly limited. For example, horse chestnut ( Aesculus turbinata Blume), horse chestnut (eel, horse chestnut) ( Aesculus hippocast )
anum L.), California Bucky ( Aesculus califo)
rnia (Spach.) Nutt.), Indian Chestnut ( Aes
culus Indica Colebr. ex Wall.), Yellow Sweet Bucky ( Aesculus octandra Marsh.), Aesculus chinensis Bunge, Aesculus w
ilsonii Rehd.), safflower ( Aesculus carnea)
Hayne), Red horse chestnut ( Aesculus pavia)
L.). There are no particular restrictions on the site of extraction of these extracts of the genus Aesculus, including bark and its mucus, fruits, seeds, seed coats, flowers, branches, leaves, roots, etc. Among them, leaves, bark, Extracts from one or more sites selected from fruits and seed coats are most preferred from the viewpoint of the effects of the present invention.

The plant of the genus Valeriana used in the present invention is a perennial herb belonging to the family Rosaceae . Examples of the plants of the genus Waremoko are not particularly limited, and examples thereof include Waremokou ( Sanguisorba officinalis L.) and Nagaboshino officinalis L. ( Sanguisorba tenuifolia Fisc).
hba var. alba Trautv. et Mey), Callitesou ( Sangu )
isorba hakusanensis Makino), the southern toe inner tank (the southern toe goldenrod) (Sanguisorba obtusa Maxim.)
, White Paniculaceae (White Paniculum) ( San
guisorba albiflora Makino, Sanguisorba obtusa Max
im. var. albiflora Makino), Galleria periwinkle (Glycine maxa) ( Sanguisorba stipulata Rafin.
, Sanguisorba sitchensis CA Mey), Dutch crested stork ( Sanguisorba minor Scop.), And Coleoptera cricket ( Sanguisorba tenuifolia Fisch.). There are no particular restrictions on the site of extraction when obtaining the extract of these plants of the genus Dipterocarp, and stems, rhizomes, roots, leaves, flowers, fruits and the like are used. Among them, the rhizome extract is advantageous in the effect of the present invention. Is most preferred.

The button genus plant used in the present invention is a herb or shrub belonging to the family Ranunculaceae . No particular limitation is imposed on the peony example, peony (sicklepod) (Paeonia albifl
ora Pall. forma hortensis Makino, Paeonia lactifl
ora Pall., Paeonia lactiflora Pall.var.trichoca
rpa (Bunge) Stern, Paeonia veichii Lynch., Paeon
ia anomala L., Paeonia mairei Levl.), Yamae peony ( Paeonia obovata Maxim. var. japonica Makino)
, Paeonia japonica Miyabe et Takeda), Buttons (Hatsukagusa, Fucamigusa, Natrigusa) ( Paeonia suffru )
ticosa Andr., Paeonia moutan Sims., Paeonia arbor
ea Donn ex Koch, Himalayan peony ( Paeonia emo)
dii Wall.ex Royle), Safflower peonies ( Paeonia o)
bovata Maxim.), Paeonia offic
inalis L.), Paeonia tenuifolia
L.). Among these button genus plants, it is particularly preferable to use one or two or more selected from peonies, yamano peonies, and buttons. The extraction site is not particularly limited, and stems, roots, leaves, flowers, fruits, and the like are used. Among them, extracts from the roots are particularly preferred from the viewpoint of the effects of the present invention.

Ginkgo ( Gink) used in the present invention
go bibloba L.) is a plant of the genus Ginkgoaceae . The extraction site is not particularly limited, and bark, sap, leaves, branches, roots, fruits, and the like are used. Among them, extracts from leaves are most preferable in view of the effect of the present invention.

The birch plants used in the present invention are plants belonging to the birch family ( Betulaceae ). The birch plants are not particularly limited, and for example, birch (birch, birch, birch, birch) ( Betula pla
typhylla Sukatchev var. japonica Hara), birch (Soushikanba) (Betula ermani Cham.), Jizoukanba (Inubushi) (Betula globispica Shirai), Betula dahurica (Koonoore) (Betula davurica Pal
l.), Udaikamba ( Betula maxim )
owicziana Regel), Azusa ( Yogsominebari ) ( Betul
a grossa Sieb. et Zucc. var . ulmifolia Makino),
Water Mizume (Azusa, Koppadaminebari) ( Betulagrossa S
ieb. et Zucc.), Virgin's birch (cat hornbill) ( Betul
a corylifolia Regel et Maxim.), onoole (Onnore, Azusaminebari) ( Betula schmidtii Regel), birch ( Betula nikoensis Koidz.), black birch ( Betulalenta L.), red birch ( Betula nigra L.).
, Betula rubra Michx.), Canoe birch ( Betula pap )
yrifera Marsh.), silver birch ( Betula pendula R)
oth., Betula verrucosa Ehrh., Betula alba L., p.
p.), European birch ( Betula pubescens Ehr
h.), Himalayan birch ( Betula utilis D. Don), red birch (Betula ermani Cham. var. subcordata (Rege
l) Koidz.). Among these plants,
Birch is most preferably used. The extraction site is not particularly limited, and bark, sap, leaves, branches, roots, nuts, and the like are used. Among them, extracts from bark are most preferred from the viewpoint of the effects of the present invention.

The parsley ( Petroselium) used in the present invention
saticum , Petroselium sativm Hoffm., Petroselium
crispum Nyman, Petroselium hortense Hoffm., Petr
oselium crispum (Mill.) Nym.ex AW Hill, Apium
petroselium L.) is a biennial herbaceous plant of the Umbelliferae family. The extraction site for obtaining the parsley extract is not particularly limited, and the whole plant or the above-ground portion of the parsley can be used, and a part of leaves, stems, roots, seeds and the like can also be used.

In the present invention, extraction solvents for obtaining extracts from these plants include water, ethanol, methanol, isopropanol, isobutanol, n-hexanol, methylamyl alcohol, 2-ethylbutanol, and n-octyl. Monohydric alcohols such as alcohol, glycerin, ethylene glycol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, triethylene glycol, 1,3-butylene glycol, One or more polar solvents such as polyhydric alcohols such as xylene glycol or derivatives thereof can be selected and used. In particular, purified water, ethanol, 1,3-
It is preferable to use butylene glycol, glycerin, and propylene glycol alone or in combination of two or more.

Examples of the extraction method include a method of immersion and extraction at room temperature, in a cooled or heated state, and a method of extraction using a distillation method such as steam distillation. These methods may be used alone or in combination of two or more. Extraction is performed by combining the above.

The ratio of the plant to the solvent at the time of extraction is not particularly limited.
~ 1000 times by weight, especially 0.5 ~ in terms of extraction operation and efficiency
100 weight times is preferred. The extraction temperature is 5 at normal pressure.
It is convenient to keep the temperature in the range from ℃ to the boiling point of the solvent, and the extraction time varies depending on the extraction temperature and the like, but is preferably in the range of 2 hours to 2 weeks.

The plant extract thus obtained can be used as it is, but it may be subjected to purification operations such as deodorization, decolorization, concentration, etc. within a range not losing the effects of the present invention. It may be used as a fraction using chromatography or the like. These extracts, deodorized products, purified products, and fractionated products can be dried by removing the solvent from them, and can be further solubilized in a solvent such as alcohol, or in the form of an emulsion. Can be blended.

In the present invention, the components in the above plant extract can be used alone or in combination. As these components, carotenoids, flavonoids, and tannins are particularly effective.

Examples of the carotenoids used in the present invention include α-carotene, β-carotene, γ-carotene, lycopene, cryptoxanthin, rutin (xanthophyll), zeaxanthin, rhodoxanthin, crocetin and the like. In addition, these carotenoids may be used as they are, or derivatives such as glycosides and esters may be used.

The natural flavonoids used in the present invention include flavones such as flavone, chrysin, primetine, apigenin, luteolin and glycosides thereof, flavonols such as galangin, kaempferol, fisetin, quercetin, myricetin and the like. These glycosides, isoflavones such as daidzein and genistein, and these glycosides, flavanones such as flavanone, pinocembrin, naringenin, sakuranetin, hesperetin, eriodictyol, and matisinol; Flavanonols and their glycosides such as pinobanksin, aromadendrin, fustin, taxifolin and amperoptin, and chalcones and their glycosides such as chalcone, butein, carconocartamidine, pedisin and pedicinin , Base Nzarukumaranon, Surufurechin, Reputoshijin, benzal Kumara Non acids and their glycosides such as Oroijin, pelargonidin, cyanidin, anthocyans such as delphinidin and its glycoside, and the like. Further, a compound having a flavonoid skeleton that does not exist in nature can also be used.

The tannins used in the present invention are tannic acids in a broad sense, which are present in many plants, particularly the bark of beech family plants such as oak and oak, leaves of gourd plants such as goby, lulude and urushi, and fruits of kariloku. It is also called gallotannin, gallotannic acid or the like. Tannins are a generic term for these complex aromatic compounds having a large number of phenolic hydroxyl groups widely distributed in the plant kingdom. Phenols and phenol carboxylic acids are obtained by alkali decomposition. In the present invention, these plant-derived tannins can be used as they are or purified, and further those artificially synthesized can be used. Further, among these tannins, it is most preferable to use hamameli tannin contained in the hamamelis extract.

In the present invention, one or more selected from superoxide dismutase, gallic acid and salts or derivatives thereof, and hydroquinone and salts or derivatives thereof can be used as other active oxygen scavengers. .

In the present invention, one or more selected from thioredoxin, thioredoxin reductase and a complex thereof can be used as an active oxygen scavenger. Furthermore, thioredoxin, thioredoxin reductase and a complex thereof can be used. An active oxygen scavenger comprising one or more selected from the body and reduced nicotinamide amide adenine dinucleotide phosphate can also be used.

In the present invention, one or more of the above active oxygen scavengers can be selected and used.
The amount of these active oxygen scavengers to be added to the external preparation for skin depends on the active oxygen scavenging ability of each plant extract or component, but is preferably about 0.0001 to 5% by weight.

[0038] The external preparation for skin according to the present invention includes oils and fats, waxes, hydrocarbons, fatty acids, lower alcohols, higher alcohols, polyhydric alcohols, esters, and the like usually used as a base for external preparation. Surfactants, water-soluble polymers and the like can be contained. Further, other skin cell activators, anti-inflammatory agents, active oxygen scavengers, whitening agents, humectants, ultraviolet absorbers, preservatives and fungicides, fragrances and the like can be contained.

The external preparation for skin according to the present invention can be provided in the form of lotions, emulsions, gels, creams, ointments and the like. Also, skin cosmetics such as lotions, emulsions, creams, beauty essences, massage agents, packs, etc., makeup cosmetics such as makeup base lotions, makeup base creams, liquid or creamy foundations, hand creams, etc. It can also be provided as a body cosmetic such as leg cream and body lotion.

[0040]

EXAMPLES Examples of the production of Agaricus mushroom extract used in Examples of the present invention are shown below.

Production Example 1 Agaricus mushroom mycelium extract An Agaricus mushroom mycelium extract was obtained by the method described in JP-B-61-47518. That is, glucose 4
g, yeast extract 4 g, malt extract 10 g, and purified water 1
A liter of a medium having a pH of 5.5 was sterilized at 120 ° C. for 20 minutes, inoculated with Agaricus mushroom mycelium cultured on an agar medium, and pre-cultured at 30 ° C. for 30 days with occasional agitation while still standing. Then, a pH of 5 g consisting of 20 g of glucose, 5 g of yeast powder, 20 ppm of an antifoaming agent and 1 liter of purified water.
2.0 liters of the main culture medium was sterilized at 120 ° C. for 20 minutes, 200 ml of the preculture was inoculated thereto, and cultured at 30 ° C. with a reciprocating shaker. After culturing for 30 days, the culture was stopped, and the mycelium was separated and collected by centrifugation. Purified water was added 7 times by weight to the mycelium, and the mixture was heated and extracted at 95 ° C. for 2 hours. The supernatant obtained by removing the residue by centrifugation was used as an Agaricus mushroom mycelium extract.

[Manufacturing Example 2] Agaricus mushroom mycelium culture filtrate At the time of preparation of Preparation Example 1, the culture solution from which the mycelium was removed from the main culture solution of the Agaricus mushroom mycelium was used as the Agaricus mushroom mycelium culture filtrate.

Next, embodiments of the present invention will be described in detail. In addition, the plant extract used in each Example used what filtered the thing which dipped the dried plant body in the solvent of 5 weight times at room temperature for 1 week.

[Examples 1 to 4, Comparative Examples 1 to 7] O / W emulsified cosmetic liquid Using each component shown in Table 1, O / W was prepared according to the following formulation.
An emulsified beauty liquid was prepared. (Prescription) (1) Squalane 5.0 (% by weight) (2) White petrolatum 2.0 (3) Beeswax 0.5 (4) Sorbitan sesquioleate 0.8 (5) Polyoxyethylene oleyl ether (20EO) 1.2 (6) Methyl paraoxybenzoate 0.1 (7) Propylene glycol 5.0 (8) Purified water Amount of which total amount becomes 100 (9) 1.0% by weight aqueous solution of carboxyvinyl polymer 20.0 (10) Hydroxide Potassium 0.1 (11) Ethanol 5.0 (12) Components shown in Table 1 Amount shown in Table 1 (13) Fragrance 0.2 Production method: The oil phase components (1) to (5) are mixed and mixed at 75 ° C. To dissolve and homogenize. On the other hand, the aqueous phase components of (6) to (8) are mixed,
Dissolve and heat to 75 ° C., add oil phase components and pre-emulsify. After adding (9), the mixture is emulsified uniformly with a homomixer, and (10) is added to adjust the pH. After cooling at 40 ° C (1
1) to (13) are added, mixed and homogenized.

[0045]

[Table 1]

Using Examples 1 to 4 and Comparative Examples 1 to 7, the effect of preventing wrinkles caused by ultraviolet rays was evaluated. The wrinkle-preventing effect was obtained by applying five hairless mice to one group, applying Examples and Comparative Examples to the back once a day for each group, and applying 1 J / cm ² / week long-wave ultraviolet light (UVA) for 50 weeks. Irradiation was performed to observe the occurrence of wrinkles in hairless mice, and scored according to the criteria shown in Table 2. At this time, a group to which only purified water was applied was used as a control. As a result, the average value of each group was calculated, and UV
The results are shown in Table 3 in relation to the A irradiation days.

[0047]

[Table 2]

[0048]

[Table 3]

As shown in Table 3, the Agaricus mushroom extract and the active oxygen scavenger were used in combination as compared with Comparative Examples 1 to 6 in which various components were blended alone or Comparative Example 7 in which no components were blended. In the examples of the present invention, the wrinkles were remarkably suppressed in spite of the small amount of each component, and the fine wrinkles were slightly generated after 50 weeks.

Subsequently, the anti-inflammatory effects of Examples 1 to 4 and Comparative Examples 1 to 7 of the present invention were evaluated.
Using 5 mice per group in which artificial inflammation was formed, 0.5 g each of Examples and Comparative Examples was applied to each group twice a day.
It was applied for one day, and the state of the inflamed site was observed on the seventh day, and evaluated in three stages of “effective”, “slightly effective”, and “ineffective”. .

[0051]

[Table 4]

As is clear from Table 4, with regard to the anti-inflammatory effect, effective anti-inflammatory effect was observed in all five mice in the group to which the present invention was applied.
Compared with Comparative Example 1 or Comparative Example 2 in which the Agaricus mushroom mycelium extract and the Agaricus mushroom mycelium culture filtrate of Production Example 1 were mixed alone in a double amount, the results were superior.

Next, a six-month actual use test was conducted on Examples 1 to 4 and Comparative Examples 1 to 7 of the present invention. As panelists, women in their 40s and 60s who have skin symptoms such as remarkable wrinkles or decreased elasticity, and women in their 20s and 50s who show remarkable skin roughening symptoms, 20 people in each group And In the use test, each group was allowed to use each of the examples and comparative examples in a blind manner, and the skin condition was observed before the start of the use test and after the end of the use test. Each improvement of wrinkles and skin elasticity was evaluated in three stages of “improvement”, “slight improvement”, and “no change”. Table 5 shows the number of panelists who obtained each evaluation.
The degree of wrinkles was evaluated by taking a photograph and a replica, and the skin elasticity was measured and evaluated by a cute meter. Regarding skin roughness, the skin condition was scored according to the criteria shown in Table 6, and the average value of the 20 subjects was compared before and after the use test with the average value of the use test.
It was shown to.

[0054]

[Table 5]

As shown in Table 5, no wrinkles and no improvement in skin elasticity were not observed in the group using the examples of the present invention, and a clear improvement was observed in 16 or more panelists. On the other hand, in Comparative Example 1 to Comparative Example 6 use group, wrinkles and an improvement tendency of elasticity were observed from Comparative Example 7 in which various components were not blended, but the number of panelists in which a clear improvement was observed was all The number was 10 or less.

[0056]

[Table 6]

[0057]

[Table 7]

As shown in Table 7, in the group using the example of the present invention, all panelists tended to improve the roughness of the skin, and almost all the panelers could clearly see the crevices and skin ridges. Was. On the other hand, in Comparative Examples 1 to 6 in which various components were blended alone, the condition of the skin was improved as compared with Comparative Example 7 in which various components were not blended. The shape remained ambiguous.

Incidentally, in Examples 1 to 4 of the present invention, no change in the state of the preparation such as precipitation, separation, aggregation, discoloration and discoloration of the contained components was observed at all during the use test period. In addition, in each group used in Examples, there was no paneler showing a skin irritating reaction or a skin sensitizing reaction.

Next, the formulation of another embodiment of the present invention will be described.

Example 5 Skin Lotion (1) Ethanol 10.0 (wt%) (2) Hydroxyethylcellulose 1.0 (3) Agaricus mushroom mycelium extract (Production Example 1) 0.2 (4) β-carotene 0.1 (5) Methyl paraoxybenzoate 0.1 (6) Purified water 88.6 Production method: Mix (1) to (6) to make uniform.

Example 6 Emulsion for Skin (1) Stearic acid 0.2 (% by weight) (2) Cetanol 1.5 (3) Vaseline 3.0 (4) Liquid paraffin 7.0 (5) Polyoxy Ethylene (10EO) monooleate 1.5 (6) Tocopherol acetate 0.5 (7) Glycerin 5.0 (8) Methyl paraoxybenzoate 0.1 (9) Triethanolamine 1.0 (10) Purified water 79.5 (11) Agaricus mushroom mycelium culture filtrate (Production Example 2) 0.5 (12) Ginkgo biloba leaf 50% by weight ethanol extract
0.2 Production method: The oil phase components (1) to (6) are mixed and heated to dissolve uniformly, and kept at 70 ° C. On the other hand, the aqueous phase components (7) to (10) are mixed and heated to be uniform, and the temperature is set to 70 ° C. The oil phase component was gradually added to the aqueous phase component while stirring to emulsify, and after cooling, (11) and (12) were added at 40 ° C.
Mix.

Example 8 Skin Gel (1) Purified Water 88.0 (% by weight) (2) Carboxyvinyl Polymer 0.5 (3) Dipropylene Glycol 10.0 (4) Methyl Paraoxybenzoate 0 0.1 (5) Potassium hydroxide 0.1 (6) Agaricus mushroom mycelium extract (Production Example 1) 0.8 (7) Parsley 50% by weight 1,3-butylene glycol extract 0.5 Preparation method: (1 After (2) is uniformly dissolved in (3), (4) is dissolved and added to (3), and then (5) is added to increase the viscosity, (6) and
(7) is added.

Example 9 Skin Cream (1) Beeswax 6.0 (% by weight) (2) Cetanol 5.0 (3) Reduced Lanolin 8.0 (4) Squalane 27.5 (5) Glyceryl fatty acid ester 4.0 (6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene (20EO) sorbitan monolaurate 5.0 (8) Propylene glycol 5.0 (9) Methyl paraoxybenzoate 1 (10) Purified water 36.88 (11) Agaricus mushroom mycelium culture filtrate (Preparation Example 2) 0.5 (12) Hamamellitannin
Production method 0.02: The oil phase components (1) to (7) are mixed and dissolved and heated to 75 ° C. On the other hand, the aqueous phase components (8) to (10) are mixed and dissolved and heated to 75 ° C. Next, the oil phase component is added to the water phase component and pre-emulsified, then uniformly emulsified by a homomixer, and after cooling, (11) and (12) are added and mixed at 40 ° C.

Example 10 Oil-in-water emulsion ointment (1) White petrolatum 25.0 (% by weight) (2) Stearyl alcohol 25.0 (3) Glycerin 12.0 (4) Sodium lauryl sulfate 1.0 (5) Methyl paraoxybenzoate 0.1 (6) Purified water 35.4 (7) Agaricus mushroom mycelium extract (Preparation Example 1) 1.0 (8) Malonier 50% by weight ethanol extract 0.5 Preparation method: The oil phase components (1) to (4) are mixed and dissolved to make uniform, and heated to 75 ° C. On the other hand, dissolve (5) in (6)
Heat to 5 ° C, add the oil phase component to this and emulsify,
After cooling, add (7) and (8) at 40 ° C and mix.

Example 11 Lotion (1) Ethanol 10.0 (wt%) (2) 1,3-butylene glycol 5.0 (3) Agaricus mushroom mycelium culture filtrate (Production Example 2) 0.1 (4) 50% by weight of oak ethanol extract 0.5 (5) Fragrance 0.1 (6) Purified water 84.3 Production method: (1) to (5) are sequentially added to (6) and mixed uniformly. Dissolve.

[Example 12] Emollient cream (water-in-oil type) (1) Liquid paraffin 30.0 (% by weight) (2) Microcrystalline wax 2.0 (3) Vaseline 5.0 (4) Diglyceryl olein Acid ester 5.0 (5) Sodium L-glutamate 1.6 (6) L-serine 0.4 (7) Propylene glycol 3.0 (8) Methyl parahydroxybenzoate 0.1 (9) Purified water 52.1 (10) Fragrance 0.1 (11) Agaricus mushroom mycelium extract (Production Example 1) 0.2 (12) Waremokou 50% by weight ethanol extract 0.5 Production method: (5), (6) to (9) Dissolved in a part of to 50 ℃,
Add slowly to (4) heated to 50 ° C. with stirring.
This was previously mixed and dissolved by heating at 70 ° C. (1)-
(3) is uniformly dispersed, and (7) and (8) are dissolved in the remainder of (9) and heated to 70 ° C. and added thereto with stirring.
Emulsify with a homomixer. After cooling, at 40 ° C (10) ~
Add (12) and mix.

Example 13 Makeup Base Cream (1) Stearic acid 12.0 (% by weight) (2) Cetanol 2.0 (3) Glyceryl tri-2-ethylhexanoate 2.5 (4) Self-emulsification Type glyceryl monostearate 2.0 (5) Propylene glycol 10.0 (6) Potassium hydroxide 0.3 (7) Purified water 68.6 (8) Titanium oxide 1.0 (9) Bengala 0.1 ( 10) Yellow iron oxide 0.4 (11) Fragrance 0.1 (12) Agaricus mushroom mycelium culture filtrate (Production Example 2) 0.5 (13) Birch 50% by weight extract 0.5 Production method: (1)- The oil phase component of (4) is mixed and heated to 75 ° C. to make it uniform. On the other hand, the aqueous phase components (5) to (7)
The mixture is heated and dissolved at 5 ° C. to make the mixture uniform, and the pigments (8) to (10) are added thereto and uniformly dispersed by a homomixer. The oil phase component is added to the aqueous phase component, emulsified by a homomixer, cooled, and (11) to (13) are added and mixed at 40 ° C.

Example 14 Emulsion Foundation (1) Stearic acid 2.0 (% by weight) (2) Squalane 5.0 (3) Octyldodecyl myristate 5.0 (4) Cetanol 1.0 (5) Decaglyceryl monoisopalmitate 9.0 (6) 1,3-butylene glycol 6.0 (7) Potassium hydroxide 0.1 (8) Methyl parahydroxybenzoate 0.1 (9) Purified water 53.4 ( 10) Titanium oxide 9.0 (11) Talc 7.4 (12) Bengala 0.5 (13) Yellow iron oxide 1.1 (14) Black iron oxide 0.1 (15) Fragrance 0.1 (16) Agaricus Mushroom mycelium extract (Production Example 1) 0.15 (17) Hamamelitannin 0.05 Production method: The oil phase components (1) to (5) are mixed and heated to 75 ° C. to make uniform. On the other hand, the aqueous phase components (6) to (9)
The mixture is heated to 5 ° C. and dissolved to make the mixture uniform, and the pigments (10) to (14) are added thereto and uniformly dispersed by a homomixer. The oil phase component is added to the aqueous phase component, and the mixture is uniformly emulsified by a homomixer, then cooled, and (15) to (17) are added and mixed at 40 ° C.

Example 15 Hand Cream (1) Cetanol 4.0 (% by weight) (2) Vaseline 2.0 (3) Liquid paraffin 10.0 (4) Glyceryl monostearate 1.5 (5) Polyoxyethylene (60EO) glyceryl isostearate 2.5 (6) Tocopherol acetate 0.5 (7) Glycerin 20.0 (8) Methyl parahydroxybenzoate 0.1 (9) Purified water 58.9 (10) Agaricus Mushroom mycelium culture filtrate (Production Example 2) 0.2 (11) Button 50% by weight ethanol extract 0.3 Production method: Mix and dissolve oil phase components (1) to (6) and heat to 75 ° C . On the other hand, the aqueous phase components (7) to (9) are mixed and dissolved and heated to 75 ° C. Next, the oil phase component is added to the water phase component and pre-emulsified, then uniformly emulsified and cooled with a homomixer, and (10) and (11) are added and mixed at 40 ° C.

[0071]

As described in detail above, an external preparation for skin using an Agaricus mushroom extract and an active oxygen scavenger in combination is excellent in preventing skin roughening and aging, and protects dermal fibroblasts from damage by ultraviolet rays. It has an effect, is effective in preventing or improving symptoms such as generation of wrinkles and decrease in skin elasticity, and has an effect of preventing or improving skin inflammation and rough skin.

Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 38/44 A61K 45/00 45/00 37/50

Claims (9)

[Claims] [1] Agaricus blazei Murill
Mycelium extract and Agaricus blazei Muril
l) one or more selected from mycelium culture filtrate;
An external skin preparation containing an active oxygen scavenger. 2. The external preparation for skin according to claim 1, wherein the active oxygen scavenger is a plant extract having an active oxygen scavenging action. 3. The external preparation for skin according to claim 1, wherein the active oxygen scavenger is a plant extract containing one or more components selected from carotenoids, flavonoids, and tannins. . 4. The method according to claim 1, wherein the active oxygen scavenger is Hamameris.
lis japonica Sieb.et Zucc., Hamamelis obtsusata M
akino, Hamamelis japonica Sieb.et Zucc.var.obtsus
ata Matsum., Hamamelis virginiana L., Hamamelis
mollis Oliv.), Quercus serrata, Horse chestnut genus, Warmkou genus, Button genus, Ginkgo ( Ginkgo bibloba L.), Birch genus, Parsley ( Petroselium saticum , Petroselium)
sativm Hoffm., Petroselium crispum Nyman, Petros
elium hortense Hoffm., Petroselium crispum (Mil
l.) An external preparation for skin according to claim 1, characterized in that it is an extract of one or more plants selected from Nym. ex AW Hill, Apium petroselium L.). 5. The external preparation for skin according to claim 1, wherein the active oxygen scavenger is hamamelitannin. 6. The skin external preparation according to claim 1, wherein the active oxygen scavenger is one or more components selected from carotenoids, flavonoids, and tannins. 7. The active oxygen scavenger is one or more components selected from superoxide dismutase, gallic acid and salts or derivatives thereof, hydroquinone and salts or derivatives thereof. 2. The external preparation for skin according to 1. 8. The external preparation for skin according to claim 1, wherein the active oxygen scavenger is one or more components of thioredoxin, thioredoxin reductase and a complex thereof. 9. The active oxygen scavenger comprises one or more components of thioredoxin, thioredoxin reductase and a complex thereof, and reduced nicotinamide amide adenine dinucleotide phosphate. Item 3. An external preparation for skin according to item 1.