JP2003040769A - Skin care preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin care preparation capable of effectively ameliorating keratinization symptom of psoriasis, ichthyosis vulgaris, palmoplantar keratosis, Darier disease, callosity, heloma or the like, dry skin, and the symptom or the like of stain, somberness and roughening of the skin, having good preparation stability, and hardly irritating the skin. SOLUTION: This skin care preparation contains (A) one or more kinds selected from the group consisting of a vegetable protease, a plant extract containing the same, and a plant extract having a protease-like activity, in combination with (B) one or more kinds selected from the group consisting of a hydroxycarboxylic acid, a salt thereof, a derivative thereof, and a plant extract containing one or more kinds of the hydroxycarboxylic acid and the like.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention can effectively remove keratin, which is thickened or parakeratosis due to abnormal keratinization, to effectively improve keratoses and skin symptoms such as skin stains and dullness. The present invention relates to an external preparation for skin which is excellent in formulation stability and safety. More specifically, one or more selected from the group consisting of a plant protease, a plant extract containing the same, and a plant extract having a protease-like activity, and a hydroxycarboxylic acid and a salt or derivative thereof, and the above. The present invention relates to a skin external preparation which is used in combination with one or more selected from the group consisting of plant extracts containing one or more hydroxycarboxylic acids.

[0002]

In the epidermis, epidermal cells are basal cells,
Differentiation called "keratinization" is carried out, in which the cells gradually change into morphologically characteristic cells such as spiny cells and granule cells, migrate to the surface layer, and finally become keratinocytes and exfoliate. This keratinization process is said to be completed in about 4 weeks on normal skin. However, due to various factors such as infection and inflammation, keratinocytes proliferate and keratin is excessively produced,
Alternatively, due to delayed exfoliation of the keratin, the keratin may accumulate to present a condition called keratosis, which is mainly characterized by keratin thickening and scaling. In addition, abnormal keratinization causes dry skin called "Dry Skin" and rough skin, and the extension of the keratinization process with aging is one of the causes of aging symptoms such as wrinkles, dullness, and dullness. ing.

It has long been disclosed that 2-hydroxy acids, 2-keto acids and their related compounds are useful for improving such keratinization symptoms (US Pat. No. 38795).
No. 37, No. 3920835). Recently, it has been proposed to use peony extract, Amaranthus cornucopiae extract, Dioscorea extract and Corydalis serrata extract in order to promote the decomposition of desmosomes involved in the adhesion mechanism of the stratum corneum and promote the exfoliation of the stratum corneum. (Japanese Patent Laid-Open No. 2000-239
121).

However, there has been a problem with external application of 2-hydroxy acids and 2-keto acids to the skin such that when used in an effective amount, it causes considerable skin irritation.
In addition, when a plant extract having a desmosome degradation promoting function is externally applied to the skin, a sufficient effect may not be obtained in some cases due to their stability and permeability in the epidermis.

[0005]

Therefore, in the present invention, abnormally generated and thickened keratin and keratin accumulated due to delayed detachment are removed to obtain psoriasis, ichthyosis vulgaris, palmoplantar keratoses, and Darriere. Keratosis such as illness, sting, chicken eye, D
ry Skin, skin stains, dullness, rough skin, etc. can be effectively improved, and the formulation stability is good,
The purpose was to obtain a skin external preparation that is mild to the skin.

[0006]

As a result of various studies to solve the above-mentioned problems, it was selected from the group consisting of (A) plant proteases, plant extracts containing them, and plant extracts having protease-like activity. 1 or 2 or more and 1 or 2 selected from the group consisting of (B) hydroxycarboxylic acid and its salts and derivatives, and a plant extract containing one or more of said hydroxycarboxylic acid and the like.
It was found that the combined use of at least one species synergistically improves the effect of removing abnormally generated or accumulated keratin and reduces skin irritation, and has completed the present invention.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Examples of the plant protease used in the present invention include papain, ficin and bromelain. Papain is a cysteine protease present in papaya emulsion and has a molecular weight of 23,40.
6. The isoelectric point is 8.75 and the optimum pH is near neutral. In addition, ficin is a cysteine protease present in fig milk emulsion, which is a glycoprotein having a molecular weight of about 26,000, and has an isoelectric point of 9 and an optimum pH in the vicinity of neutrality. Bromelain is then the major cysteine protease of plants belonging to the family Pineapple. The stem bromelain contained in the rhizome of pineapple is composed mainly of a basic glycoprotein having a molecular weight of 28,000, and the flute bromelain contained in the fruit of pineapple has a molecular weight of 31,000.
The main component is acidic simple protein. In the present invention, these may be extracted from plants belonging to the family papaya, fig and pineapple, separated and purified for use, but it is convenient to use those commercially available for pharmaceuticals and the like.

[0008] The plant extract containing plant proteases, fig (Ficus carica L.), kiwi (Acti
nidia chinensis Planch.), sprouted corn ( Zea m
ays L.), a plant belonging to the family Bromeliaceae , Carica papaya L., Cucuoli
mis melo L.) and Japanese yam ( Dioscorea japonica Thu)
Each of nb.) extracts are mentioned as preferred ones.

[0009] Fig ( Ficus carica L.) is a mulberry ( M
Oraceae ) deciduous tree, and it is preferable to use branches, leaves and fruits for extraction. In particular, it is preferable to use the milky lotion secreted from the cut end of each part.

Kiwi ( Actinidia chinensis Planch.)
It is also known as Cinnamon pear ( Actinidiac).
It is a vine that belongs to eae ) and it is preferable to use fruits for extraction.

Corn ( Zea mays L.) is a gramineous plant ( G
ramineae ), which is a large annual plant, and germinated seeds are used in the present invention.

The plants belonging to the pineapple family ( Bromeliaceae ) include the genus Coral Ananas ( Aechmea ), the genus Ananas, and the genus Billbergia .
Genus Bromelia, Genus Cryptanthus , Dyckia
Genus, Guzmania genus, Neoregeria
elia ), Ochagavia , Caviana ( Pitcairni)
Examples include plants belonging to the genus a ), the genus Puya, the genus Tillandsia, the genus Incoreanas ( Vriesea ), and the like. Among these, pineapple ( Ananas comosus Me
Plants belonging to the genus Pineapple ( Ananas ) such as rrill) and its variants are preferably used. It is preferable to use rhizomes and fruits for extraction.

Papaya ( Carica papaya L.) is a herbaceous tree belonging to the family Papaya ( Caricaceae ), and it is preferable to use fruits. In particular, it is preferable to use an emulsion that damages the fruit and exudes.

Cucumis melo L. is an annual creeping herb belonging to the family Cucurbitaceae , and melons which are varieties thereof are preferably used. It is preferable to use fruits for extraction.

Dioscorea japonica Thun
b.) is a creeping perennial belonging to the family Dioscoreaceae , and it is preferable to use potato.

For the extraction of the above plants, an aqueous solvent such as water, physiological saline, phosphate buffer, phosphate buffered saline, etc. is used,
It is preferable to carry out at a temperature as low as possible. In addition, the extraction efficiency can be increased by adding a surfactant to the extraction solvent.

Examples of the plant extract having a protease-like action include plants belonging to the genus Tilia . Examples of plants belonging to the genus Tilia are Tilia americana L., Tilia cordata Mill., And Tilia e.
uropaea L.), linden ( Tilia japonica Simonk.),
Heranoki (Tilia kiusiana Makino et Shiras.) , Oba linden (Tilia maximowicziana Shiras.), Linden (Tilia miqueliana Maxim.), Tilia Platyphyllos (Tilia platyphyllos Scop.) And the like. These are deciduous trees belonging to the linden family ( Tiliaceae ),
Flowers, leaves and bark are preferably used.

As the extraction solvent, in addition to water, methanol,
Lower alcohols such as ethanol, propanol and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol and glycerin, ethers such as ethyl ether and propyl ether, esters such as ethyl acetate and butyl acetate. It is possible to use polar organic solvents such as acetone, ketones such as ethyl methyl ketone, etc., and one kind or two or more kinds are selected from these and used. Alternatively, physiological saline, phosphate buffer, phosphate buffered saline, etc. may be used.

The plant containing the above-mentioned plant protease and the plant having a protease-like activity may be used for extraction as they are.
Extraction is preferably carried out after treatments such as drying and crushing. The extraction is performed by immersing it in an extraction solvent. It may be stirred or homogenized in an extraction solvent in order to improve the extraction efficiency. As the extraction temperature, a temperature of about 5 ° C to 50 ° C is suitable. The extraction time varies depending on the type of extraction solvent and the extraction temperature, but it is suitable to be about 4 hours to 14 days. Also, squeeze the plant,
It is also possible to use a plant fluid obtained by scratching the plant or a solution obtained by dissolving it in various solvents.

The plant-containing protease-containing plant and the plant extract having a protease-like activity can be contained as they are in the external preparation for skin according to the present invention. It may be used again after being redissolved in a solvent, or subjected to purification treatment such as decolorization, deodorization, and desalting within a range that does not impair the protease activity or protease-like action, or after fractionation treatment by column chromatography or the like. Good. It can also be used by encapsulating it in vesicles such as liposomes or in microcapsules.

In the present invention, one kind or two or more kinds are selected from the above-mentioned plant proteases, plant extracts containing them, and plant extracts having a protease-like action. As a blending amount based on the total amount of the skin external preparation, for plant protease, 0.00001 to
About a plant extract containing about 1.0% by weight of a plant protease or a plant extract having a protease-like action varies depending on its preparation method, but 0.0001-
It is suitable to set it to about 10.0% by weight.

Next, in the present invention, as the hydroxycarboxylic acid used in combination with one or more selected from the group consisting of plant proteases, plant extracts containing them, and plant extracts having a protease-like activity, , Those having a hydroxyl group at the 2- or 3-position having 2 to 30 carbon atoms are preferable, and 2-hydroxyethanoic acid (glycolic acid),
2-hydroxypropanoic acid (lactic acid), 2-methyl-2-hydroxypropanoic acid (methyllactic acid), 2-hydroxybutanoic acid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, 2-hydroxyheptanoic acid, 2-hydroxy Octanoic acid, 2-hydroxynonanoic acid, 2-hydroxydecanoic acid, 2-
Hydroxyundecanoic acid, 2-hydroxydodecanoic acid (2-
Hydroxylauric acid), 2-hydroxytetradecanoic acid (2-hydroxymyristic acid), 2-hydroxyhexadecanoic acid (2-hydroxypalmitic acid), 2-hydroxyoctadecanoic acid (2-hydroxystearic acid), 2-hydroxyeicosanoic acid (2-hydroxyarachidic acid), 2-hydroxytetracosanoic acid (cerebronic acid), 2-hydroxy
-9-undecenoic acid (2-hydroxy-9-undecylenic acid),
2-hydroxy-10-undecenoic acid (2-hydroxy-10-undecylenic acid), 2-hydroxy-cis-15-tetracosenoic acid (2-hydroxynervonic acid), long-chain 2-hydroxy fatty acid derived from lanolin, 3-hydroxy Propanoic acid, 2-methyl-3
-Hydroxypropanoic acid, 3-hydroxybutanoic acid, 3-hydroxypentanoic acid, 3-hydroxyhexanoic acid, 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, 3-hydroxynonanoic acid, 3-hydroxydecanoic acid, 3-hydroxy Undecanoic acid, 3-hydroxydodecanoic acid (3-hydroxylauric acid), 3-hydroxytetradecanoic acid (3-hydroxymyristic acid), 3-hydroxyhexadecanoic acid (3-hydroxypalmitic acid), 3-hydroxyoctadecanoic acid (3- Hydroxystearic acid), 3-hydroxyeicosanoic acid (3-hydroxyarachidic acid), 3-hydroxytetracosanoic acid, 3-hydroxy-9-undecenoic acid (3-hydroxy-9-undecylenic acid), 3-hydroxy-10 -Undecenoic acid (3-hydroxy-10-undecylenic acid), and 3-hydroxy-cis-15-tetracosenoic acid (3-hydroxynel) Boric acid), salicylic acid, 2,3-dihydroxypropanoic acid (glyceric acid), erythronic acid, threonic acid, etc. 2,3,4-trihydroxybutanoic acid, ribbon acid, arabinonic acid, xylonic acid, lyxonic acid, etc. 2 Such as 3,3,4,5-tetrahydroxypentanoic acid, allonic acid, altronic acid, gluconic acid, mannonic acid, gulonic acid, idonic acid, galactonic acid, and taronic acid
2,3,4,5,6-Pentahydroxyhexanoic acid, glucoheptonic acid, galactoheptonic acid and other 2,3,4,5,6,7-hexahydroxyheptanoic acid, hydroxymethanedicarboxylic acid (tartronic acid), 1- Hydroxyethane-1,2-dicarboxylic acid (malic acid), 1,2-dihydroxyethane-1,2-dicarboxylic acid (tartaric acid), 2-hydroxypropane-1,2,3-tricarboxylic acid (citric acid), glucar Acid, mutic acid, etc. 1,2,
3,4-tetrahydroxybutane-1,4-dicarboxylic acid and the like can be mentioned. As salts of these hydroxycarboxylic acids,
Alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, ammonium salts, alkanolamine salts such as triethanolamine salts, D-, L- or DL-arginine, lysine, histidine Basic amino acid salts and the like. Examples of these derivatives include alkyl or alkenyl esters, phosphoric acid esters, sulfuric acid esters, phosphatidyl esters, sterol esters such as cholesteryl ester, sitosteryl ester, and stigmasteryl ester, amides and the like. Among these, lactic acid, citric acid, succinic acid, tartaric acid, malic acid, salicylic acid and salts and derivatives thereof are particularly preferably used. Regarding the hydroxycarboxylic acid or the like, any isomer may be used as long as it has structural isomers, stereoisomers or optical isomers.

In the present invention, a plant extract containing the above-mentioned hydroxycarboxylic acid or the like may be used. Such plants include apricot ( Prunus armeniaca L. var.
ansu Maxim.), Knotweed ( Polygonum cuspidatum Sie
b. et Zucc.) and its variants and related species, strawberries ( Fra
garia) plants belonging to the genus, plum (Prunus mume Sieb.et Z
ucc.), plants belonging to the genus Rubus , Acer saccharum Marsh., Sacchar
um officinarum L.), Sanshuyu ( Cornus officinali
s Sieb. et Zucc.), Quisqualis indica L.
var. villosa Clarke), Indian Shikushi ( Qusqualis )
indica L.), plants belonging to the genus Vaccinium , Schisandra chinensis Baill., tomato ( Solanum lycopersicum L.), jujube ( Zizyphus )
vulgaris Lam. var. inermis Bunge), loquat ( Eriobotr )
ya japonica Lindl.), Bokeh ( Chaenomeles lagenaria )
Koids.), Kusaboke (Chaenomeles japonica Lind
l.), Yodoke ( Chaenomelesspeciosa Nakai), Karin ( Chaenomeles sinensis Koenne), Citrus ( Citru )
plant belonging to the genus s ), longan ( Euphoria longana La
m.), apple ( Malus pumila Miller var. dom)
estica Schneider) and Waringo ( Malus pumila Miller)
var. dulcissima Koidz.) etc. are exemplified.

Apricot ( Prunus armeniaca L. var. Ansu
Maxim.) Is a deciduous small tree belonging to Rosaceae ,
It is the base plant of the crude drug " Kyonin ( Ameniacae Semen )". For the purposes of the present invention, it is preferable to use fruits.

Polygonum cuspidatum Sieb. E
t Zucc.) is a perennial plant belonging to the family Polygonaceae , and it is preferable to use stems or roots. This variety includes the Polygonum cuspidatum Sieb. Et Zu
cc. Forma colorans Makino), Western knotweed ( Polyg
onum cuspidatum Sieb. et Zucc. var . spectabilis Ma
kino), Yellow knotweed ( Polygonum cuspidatum Sieb.
et Zucc. var. variegatum Makino), Polygonum cuspidatum Sieb. et Zucc. var. hac
hidyoense Ohwi) and the like. Another closely related species is the Polygonum sachalinense Fr. Schm.
) And the like.

[0026] Examples of the strawberries (Fragaria) plant belonging to the genus, strawberry (Fragaria ananassa Duch.), Fragaria Iinumae (Fragaria iinumae Makino), thyme strawberry (Fragaria moschata Duch.), Moriichigo (Fragari
a nipponica Makino), Strawberry strawberry ( Fragaria ves)
ca L.), Strawberry ( Fragarria yezoensis Hara)
Etc. are illustrated. These are perennials belonging to Rosaceae and it is preferable to use fruits.

Ume ( Prunus mume Sieb. Et Zucc.) Is a deciduous small tree belonging to Rosaceae , and it is preferable to use fruits.

The plants belonging to the genus Rubus are Rubus allegheniensis Port., Chishima Strawberry ( Rubus arcticus L.) and Fuyu Strawberry ( Rubus b ).
uergeri Miq.), Horomui strawberry ( Rubus chamaemorus )
L.), Gosho strawberry ( Rubus chingii Hu), Bear strawberry ( Rubus crataegifolius Bunge), Oni strawberry ( Rubuse )
llipticus Sm.), Strawberry ( Rubus frutico)
sus L.), Himefuyu strawberry ( Rubus hayata-koidzumii N
aruhashi), Rubus hirsutus Thunb.,
European Raspberries ( Rubus idaeus L.), Rose Strawberries ( Rubus illecebrosus Focke), Niga Strawberries ( Rubus mi )
crophyllus L. f.), strawberry ( Rubus molucc)
anus L.), Blackberry ( Rubus occidentalis)
L.), Momijiichigo (Rubus palmatus Thunb.), Native raspberry (Rubus parvifolius L.), Tsurukogane strawberry (Rubus pedatus JE Smith), wine raspberry (Rub
us phoenicolasius Maxim.), rose strawberries ( Rubus )
rosaefolius Smith), Strawberry ( Rubus siebold)
ii Bl.), koji strawberry ( Rubus trifidus Thunb.), safflower strawberry ( Rubus vernus Focke) and the like.
These are herbs or shrubs belonging to Rosaceae and it is preferable to use fruits.

Acer saccharum Marsh.
Is a deciduous tree belonging to the Aceraceae family, and leaves and trunks are preferably used. This sap is also preferably used.

Sugar cane ( Saccharum officinarum L.)
Is a large perennial herb belonging to the Gramineae family,
It is preferable to use a stem.

Sanshuyu ( Cornus officinalis Sieb. E
t Zucc.) is a deciduous small tree belonging to the Cornaceae family, and it is preferable to use ripe fruits.

Quisqualis indica L. var. Vi
llosa Clarke) and Indian stag beetle ( Quisqualis indic)
a L.) is a vine that belongs to the family Combretaceae and is preferably fruit.

Plants belonging to the genus Vaccinium include low-bush blueberry ( Vaccinium angust
ifolium Ait.), Rabbit Eye Blueberry ( Vaccin
iumashei Reade.), Highbush Blueberry ( Vac
cinium australe Small), Shashanbo ( Vaccinium b
racteatum Thunb.), Usuoki ( Vaccinium hirtum Thun)
b.), Akshiba ( Vaccinium japonicum Miq.), Cranberry ( Vacciniummacrocarpon Ait.), Bilberry ( V
accinium myrtillus L.), Natsuhaze ( Vaccinium oldha
mi Miq.), Vaccinium oxycoccus
L.), iwatsutsuji ( Vaccinium praestans Lamb.), Vaccinium smallii A. Gray var. Glabrum Koid
z.), black agate ( Vaccinium uliginosum L.), cowberry ( Vaccinium vitis-idaea L.) and the like. These are evergreen or deciduous shrubs belonging to the Ericaceae family, and fruits are preferably used.

[0034] Schisandra chinensis
Baill.) Is a deciduous tree belonging to the family Schisandraceae , and the herb medicine " Schisandrae Fructu "
s ) ”is the basic plant. For the purposes of the present invention it is preferred to use mature fruits.

Tomato ( Solanum lycopersicum L.) is an annual or perennial herb belonging to the Solanaceae family, and its fruit is preferably used.

Jujube ( Zizyphus vulgaris Lam. Var. In
ermis Bunge) is a deciduous small tree belonging to the family Rhamnaceae , and the herbal medicine " Zizyphi Fructu "
s ) ”is the basic plant. For the purposes of the present invention, it is preferable to use fruits.

Loquat ( Eriobotrya japonica Lindl.) Is an evergreen tree belonging to Rosaceae , and it is preferable to use leaves or fruits.

Bokeh ( Chaenomeles lagenaria Koids.),
Chestnut ( Chaenomeles japonica Lindl.), Chadome ( Chaenomeles speciosa Nakai) and Cullin ( Chaenome )
les sinensis Koenne) is a deciduous small shrub belonging to Rosaceae , and its fruit is preferably used.

Plants belonging to the citrus genus ( Citrus ) include lime ( Citrus aurantifolia Swingle), daidai ( Citrus aurantium L.) and bergamot ( Citrus be ).
rgamia Risso et Poit.), Buntan ( Citrus grandis O
sbeck), Hassaku ( Citrus hassaku Hort. ex Tanak
a), Citrus iyo Hort. ex Tanaka, Citrus junos Sieb. ex Tanaka, Citrus kinokuni Hort. exTanaka, Lemon Citrus
limon Burm.), citron (Citrus medica L.), Bushukan (Citrus medica L. var. sarcodactylis Swingl
e), Natsumikan ( Citrus natsudaidai Hayata), Grapefruit ( Citrus paradisi Macf.), Ponkan ( C
itrus reticulata Blanco), sweet orange ( Citru
s sinensis Osbeck), navel orange ( Citrus sine
nsis Osbeck var. brasiliensis Tanaka), Kavos ( Ci
trus sphaerocarpa Hort. ex Tanaka), Sudachi ( Citru
s sudachi Hort. ex Tanaka), Sampoukan ( Citrus
sulcata Hort. ex Takahashi), Citrus tac
hibana Tanaka), Citrus unshiu M
arcovitch) and the like. These are Rutaceae ( Rutac
eae ) which is an evergreen shrub or tree, and fruits are preferably used in the present invention.

Longan ( Euphoria longana Lam.) Is an evergreen tree belonging to the family Sapindaceae , and its fruits are preferably used.

Malus pumila Miller va
r. domestica Schneider) and Warring ( Malus pumila )
Miller var. Dulcissima Koidz.) Is a Rosaceae ( Rosace)
It is a deciduous tree belonging to ae ), and it is preferable to use fruits.

The plant containing the hydroxycarboxylic acid or the like may be subjected to extraction as it is, but in consideration of the extraction efficiency, it is preferable to carry out the extraction after performing treatments such as shredding, drying and crushing. . The extraction is performed by immersing it in an extraction solvent.
It may be stirred or homogenized in an extraction solvent in order to improve the extraction efficiency. As the extraction temperature, it is appropriate to set the temperature to about 5 ° C. to a temperature not higher than the boiling point of the extraction solvent. The extraction time varies depending on the type of extraction solvent and the extraction temperature, but it is suitable to be about 4 hours to 14 days. In addition, a plant fluid obtained by squeezing the plant or scratching the plant, or a solution obtained by dissolving it in various solvents can also be used.

As the extraction solvent, in addition to water, methanol,
Lower alcohols such as ethanol, propanol and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol and glycerin, ethers such as ethyl ether and propyl ether, esters such as ethyl acetate and butyl acetate. It is possible to use polar organic solvents such as acetone, ketones such as ethyl methyl ketone, etc., and one kind or two or more kinds are selected from these and used. Alternatively, physiological saline, phosphate buffer, phosphate buffered saline, etc. may be used.

The extract of the plant containing hydroxycarboxylic acid or the like with the above solvent can be contained in the external preparation for skin according to the present invention as it is, but the concentrated and dried product is redissolved in water or a polar solvent. Alternatively, it may be used after purification treatment such as decolorization, deodorization, desalting or the like within a range that does not impair these physiological actions, or after fractionation treatment by column chromatography or the like. It can also be used by encapsulating it in vesicles such as liposomes or in microcapsules.

In the present invention, one kind or two or more kinds are selected from the group consisting of the above-mentioned hydroxycarboxylic acid and salts and derivatives thereof, and a plant extract containing at least one kind of the hydroxycarboxylic acid and the like. , Contained in a skin external preparation. The amount of the compound to be applied to the external preparation for skin is about 0.0001 to 5.0% by weight for hydroxycarboxylic acid and salts and derivatives thereof, and it varies depending on the preparation method for plant extract containing hydroxycarboxylic acid and the like. However, it is appropriate that the amount be about 0.0001 to 10.0% by weight.

The external preparation for skin according to the present invention can be provided in various dosage forms such as lotions, emulsions, gels, creams and ointments. Also, skin cosmetics such as lotion, emulsion, cream, beauty essence, pack, cleansing lotion, cleansing cream, cleansing foam and other cleaning cosmetics, hand cream, leg cream,
It can be provided as body cosmetics such as neck cream, body lotion, lotion for elbows and heels.

The external preparation for skin according to the present invention includes, in addition to plant proteases and plant extracts containing them, hydroxycarboxylic acids and the like and plant extracts containing them, an oily component, a surfactant, Common raw materials for pharmaceuticals and cosmetics such as moisturizers, pigments, UV absorbers, antioxidants, fragrances, antifungal agents, anti-inflammatory agents, skin cell activators,
A physiologically active ingredient such as a whitening agent, an animal tissue extract or an extract of a plant other than the above may be contained.

[0048]

EXAMPLES The features of the present invention will be described in detail with reference to Examples.

First, the plant proteases contained in the examples of the present invention, the plant extracts containing them, the hydroxycarboxylic acids and the plant extracts containing them will be described.

For papain and ficin, commercially available purified products were used. Regarding bromelain, stem bromelain and flute bromelain isolated from pineapple stem and fruit were used.

As the plant extract containing the plant protease, each extract of kiwi, pineapple, makuwari and germinated corn prepared as follows was used. That is, kiwi ( Actinidia chinensis Planc
h.) fruit, pineapple ( Ananas comosus Merrill)
150 g of each of the fruit of Escherichia coli, Cucumis melo L. and germinated seed of corn ( Zea mays L.) were crushed with a mill, put in 1 liter of purified water, and extracted by stirring at 5 ° C. for 3 days. The extract was filtered to collect the filtrate, which was concentrated under reduced pressure and freeze-dried to obtain each of the extracts.

As the plant extract having protease-like activity, the extracts of linden, fujuboju and bodaiju prepared in the following manner were used. That is,
Leaf and flower of linden ( Tilia japonica Simonk.) 10 each
0g, 100g each of leaves and flowers of Tilia cordata Mill., Tilia miqueliana Maxi
200 g of each flower was immersed in 1.5 liter of 50% by volume aqueous ethanol solution and allowed to stand at 25 ° C. for 7 days for extraction. The extract was filtered to collect the filtrate, which was concentrated under reduced pressure and freeze-dried to obtain each of the extracts.

As the hydroxycarboxylic acid and its salt, those commercially available for pharmaceuticals and cosmetics were used.

As the plant extract containing hydroxycarboxylic acid and the like, those prepared as follows were used.

[Extracts of Apricot, Apple, and Daidai] Apricot ( Prunus armeniaca L. var. Ansu Maxi
m.) fruit, Atlantic apple ( Malus pumila Miller va
r. domestica Schneider) fruit and red sea bream ( Citrus
aurantium L.) 300 g of each fruit was squeezed, and the obtained juice was concentrated and dissolved in 500 ml of glycerin to obtain each of the title extracts.

[Extracts of jujube and loquat] Jujube ( Zizy
fruit of phus vulgaris Lam. var. inermis Bunge) 25
0 g and loquat ( Eriobotrya japonica Lindl.) Leaf 30
0 g of each was dried and crushed to obtain 50% by volume of ethanol 1
After being immersed in liter and allowed to stand at 20 ° C. for 10 days for extraction, the extract was filtered and the filtrate was collected to obtain each of the title extracts.

[Each Strawberry and Tomato Extract] Strawberry ( Fr
agaria ananassa Duch.) fruit and tomato ( Solanum l
250 g each of the fruits of ycopersicum L.) were milled in 1.2 liters of purified water in a mill at 10 ° C. and then extracted at 10 ° C. for 3 days with stirring. The extract was filtered to collect the filtrate, which was concentrated under reduced pressure and then freeze-dried to obtain each of the title extracts.

[Each extract of sugar cane, lemon and bilberry] Stem 3 of sugar cane ( Saccharum officinarum L.)
50g, 300g of lemon ( Citrus limon Burm.) Fruit
And bilberry ( Vaccinium myrtillus L.) fruit 32
0 g of each was ground with a mill, immersed in 2 liters of 1,3-butylene glycol and extracted at 15 ° C. for 14 days.
The extract was filtered and the filtrate was collected and used as each of the title extracts.

[Sugar maple extract] Sugar maple ( Ac
er saccharum Marsh.) 200 ml of sap collected by injuring the trunk of the er saccharum Marsh.) was concentrated and then dissolved in 1 liter of purified water to obtain the title extract.

Next, the formulations of the examples according to the present invention will be shown.

Example 1 Lotion Agent (1) Ethanol 20.00 (wt%) (2) Polyoxyethylene (60 E.O.) hydrogenated castor oil 1.00 (3) Dipropylene glycol 5.00 (4 ) 1,3-butylene glycol 10.00 (5) papain 0.02 (6) sodium L-lactate 0.20 (7) methyl paraoxybenzoate 0.10 (8) purified water 63.68 Production method: (1) (2) is dissolved in and the alcohol phase is obtained. on the other hand,
(3) to (7) are sequentially dissolved in (8) to form an aqueous phase. The alcohol phase is added to the aqueous phase, and the mixture is stirred and mixed.

Example 2 Emulsion (1) Cetanol 1.00 (wt%) (2) Beeswax 0.50 (3) Vaseline 2.00 (4) Squalane 6.00 (5) Dimethylpolysiloxane 2.00 (6) Polyoxyethylene (20 E.O.) sorbitan 1.00 Monostearic acid ester (7) Glyceryl monostearic acid ester 1.00 (8) Glycerin 4.00 (9) 1,3-Butylene glycol 4.00 (10) Methyl paraoxybenzoate 0.10 (11) Purified water 67.33 (12) Carboxyvinyl polymer 10.00 (1.0% by weight aqueous solution) (13) Potassium hydroxide (10.0% by weight aqueous solution) 1 0.000 (14) Ficin 0.01 (15) Stem bromelain 0.01 (16) L-sodium citrate 0.05 Manufacturing method: Mix the oil phase components (1) to (7) and heat to dissolve. 75
℃. On the other hand, the water phase components (8) to (11) are mixed and dissolved to 75 ° C. After adding the oil phase to the mixture and pre-emulsifying it, (12) was added and the mixture was uniformly emulsified with a homomixer, then (13) was added to thicken and then cooled, and the mixture was cooled at 40 ° C (14 ° C). )
~ (16) are added and mixed.

[Example 3] Gel agent (1) Dipropylene glycol 10.00 (wt%) (2) Carboxyvinyl polymer 0.50 (3) Potassium hydroxide (10.0 wt% aqueous solution) 1.00 ( 4) Methyl paraoxybenzoate 0.10 (5) Kiwi extract 0.20 (6) Linden extract 0.20 (7) Apricot extract 0.25 (8) Purified water 87.75 Manufacturing method: (8) Dissolve (2), (5) to (7) uniformly, then add to (1)
(4) is dissolved and added, and then (3) is added to thicken.

[Example 4] Oil-in-water cream (1) Beeswax 6.00 (wt%) (2) Cetanol 5.00 (3) Reduced lanolin 8.00 (4) Squalane 27.50 (5) Glyceryl Fatty acid ester 4.00 (6) Lipophilic glyceryl monostearate 2.00 (7) Polyoxyethylene (20 E.O.) sorbitan 5.00 Monolaurate (8) Propylene glycol 5.00 (9) Paraoxy Methyl benzoate 0.10 (10) Purified water 37.00 (11) Bodaiju extract 0.10 (12) Daidai extract 0.05 (13) Sugarcane extract 0.05 (14) Lemon extract 0.05 (15) Bilberry extract 0.05 (16) Sugar maple extract 0.10 Production method: Mix and dissolve the oil phase components (1) to (7) to 75 ° C. On the other hand, the water phase components (8) to (10) are mixed and dissolved, and 75
Heat to ℃. Next, the oil phase component is added to this aqueous phase component to pre-emulsify it, then homogenize with a homomixer, and after cooling, (11) to (16) are premixed and added at 40 ° C.

[Example 5] Oil-in-water emulsion type 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 34.8 (7) Flute bromelain 0.1 (8) Jujube extract 2.0 Production method: Mix the oil phase components of (1) to (4) , Heat to dissolve evenly to 75 ℃. On the other hand, mix the water phase components of (5) and (6),
Heat to 75 ° C. The oil phase component was gradually added to this water phase component while stirring to emulsify and cool the mixture.
Add (7) and (8) at ℃ and mix.

Example 6 Soft Lotion (1) Polyoxyethylene (60 E.O.) hydrogenated castor oil 0.500 (wt%) (2) Polyoxyethylene (20 E.O.) sorbitan 0.500 coconut Oil fatty acid ester (3) 1,3-butylene glycol 3.000 (4) Glycerin 1.000 (5) Trimethylglycine 1.000 (6) Hydroxyethyl cellulose 0.500 (7) Chitosan 0.001 (8) L- Citric acid 0.001 (9) L-sodium citrate 0.050 (10) Potassium hydroxide (10.0 wt% aqueous solution) 0.100 (11) Dipotassium glycyrrhizinate 0.500 (12) Isomerized sugar mixture 0 .500 (13) Euphorbiaceae extract 0.500 (14) Cornflower extract 0.500 (15) Linden extract 0.500 (16) Daidai extract 0.500 (17) Sugar cane extract 0.500 (18) Lemon extract 0.500 (19) Bilberry extract 0.500 (20) Sugar maple extract 0.500 (21) Ethanol 0.500 (22) Methyl paraoxybenzoate 0.150 (23) Fragrance 0.010 (24) Purified water 87.778 Manufacturing method: (1) and (2) are heated and dissolved, and (22) and (23) are dissolved in (21). These are sequentially added to (24) together with (3) to (20), and they are uniformly mixed and dissolved. In addition, as the isomerized sugar mixture of (12), “Pentabitine” from Pentafarm
What was marketed by the brand name of was used. In addition, as (13) the honeysuckle mallow extract and (14) the cornflower extract, the roots of honeysuckle mallow ( Althaea officinalis L.) and cornflower ( Centaurea cyanus L.) flowers 3 each
An extract with 00 g of 50% by volume aqueous ethanol was used.

Example 7 Beauty Serum (1) Stearic Acid 0.5000 (wt%) (2) Behenyl Alcohol 1.0000 (3) Glyceryl Monostearate 1.000 (4) Squalane 0.5000 (5) Jojoba oil 0.5000 (6) Beeswax 0.5000 (7) Methylphenylpolysiloxane 10.0000 (8) Glyceryl tri-mixed fatty acid 1.0000 (C12-20) ester (9) Glycyrrhetinic acid stearyl 0.0500 ( 10) d-δ-tocopherol 0.0100 (11) sorbitan monostearate 0.5000 (12) polyoxyethylene (60 E.O.) glyceryl 1.0000 monostearate (13) polyethylene glycol (25E.O) .) 1.5000 Monostearate (14) 1,3-Butyling Cole 3.0000 (15) N-stearoyl-L-sodium glutamate 0.2000 (16) Xanthan gum 0.0500 (17) Hydroxyethyl cellulose 0.0500 (18) Purified water 69.3185 (19) Chitosan 0.0005 (20) ) L-citric acid 0.0010 (21) Isomerized sugar mixture 0.2000 (22) Linden extract 0.5000 (23) Daidai extract 0.5000 (24) Sugarcane extract 0.5000 (25) Lemon extract Product 0.5000 (26) Bilberry extract 0.5000 (27) Sugar maple extract 0.5000 (28) Ethanol 0.5000 (29) Methyl paraoxybenzoate 0.0500 (30) Perfume 0.0700 Production method: (1 ) ~ (13) oil phase components are mixed and heated to dissolve 7
Set to 5 ° C. On the other hand, the aqueous phase components (14) to (18) are mixed and dissolved to 75 ° C. The oil phase is added to this and pre-emulsified, and then uniformly emulsified with a homomixer and cooled to 40 ° C.
(19) to (27) are sequentially added at, mixed and dissolved, and then (2
Dissolve 9) and (30) in (28) and add and mix. Note that (21)
As the isomerized sugar mixture of, a commercially available product under the trade name of “Pentabitine” from Pentafarm was used.

Example 8 Cleaning Lotion (1) Ethanol 15.00 (wt%) (2) Polyoxyethylene (20 E.O.) Sorbitan 1.00 Monolauric Acid Ester (3) Polyoxyethylene Polyoxy Propylene 1.50 Block polymer (4) Perfume 0.10 (5) Methyl paraoxybenzoate 0.10 (6) Glycerin 6.00 (7) 1,3-Butylene glycol 6.00 (8) Polyethylene glycol (average molecular weight 400) 6.00 (9) Pineapple extract 0.15 (10) L-malic acid 0.02 (11) L-sodium tartrate 0.05 (12) Purified water 64.08 Manufacturing method: (1) to (2) )-(5) are dissolved to make an alcohol phase.
On the other hand, (6) to (11) are sequentially dissolved in (12) to form an aqueous phase. The alcohol phase is added to the aqueous phase, and the mixture is stirred and mixed.

Example 9 Jelly-like Packing Agent (1) Ethanol 5.0 (wt%) (2) Polyoxyethylene (20E.O.) Sorbitan 1.0 Monolaurate (3) Methyl paraoxybenzoate 0 .1 (4) Perfume 0.1 (5) Polyoxyethylene glycol 5.0 (average molecular weight 1,500) (6) Glycerin 5.0 (7) Sorbitol 5.0 (8) Carboxyvinyl polymer 1.0 ( 9) Xanthan gum 0.5 (10) Mackerel extract 0.1 (11) Fuyudaidai extract 0.2 (12) Loquat extract 0.2 (13) Purified water 71.8 (14) Potassium hydroxide (10 Wt% aqueous solution) 5.0 Production method: Mix (1) to (4) and dissolve to make an alcohol phase.
On the other hand, (5) to (12) are sequentially added to (13) to be dissolved, and the alcohol phase is added to this to be solubilized. Then, (14) is added to neutralize.

Example 10 Lotion for Elbow / Knee (1) Ethanol 10.0 (wt%) (2) Polyoxyethylene (20 E.O.) Sorbitan 0.5 Monolauric Acid Ester (3) Paraoxybenzoic Acid Methyl 0.1 (4) Perfume 0.1 (5) Methylcellulose 0.2 (6) Quinceseed 0.1 (7) Glycerin 4.0 (8) 1,3-Butylene glycol 6.0 (9) Polyoxy Ethylene glycol 5.0 (average molecular weight 1,500) (10) Corn germinated seed extract 0.5 (11) Atlantic apple extract 0.2 (12) L-sodium lactate 0.2 (13) Purified water 73. 1 Manufacturing method: (1) to (4) are mixed and dissolved to obtain an alcohol phase.
On the other hand, (5) and (6) were dissolved in a part of (13) to prepare a viscous liquid, and (7) to (12) were dissolved in the rest of (13) and added to the aqueous phase. To do. The alcohol phase is added to this aqueous phase and mixed uniformly.

Example 11 Cleansing Lotion (1) Stearyl Alcohol 0.50 (wt%) (2) Hardened Palm Oil 3.00 (3) Squalane 35.00 (4) Sorbitan Sesquioleate 1.60 ( 5) Polyoxyethylene (20 E.O.) oleyl ether 2.40 (6) 1,3-butylene glycol 6.00 (7) Polyethylene glycol (average molecular weight 400) 4.00 (8) Strawberry extract 0.30 (9) Methyl paraoxybenzoate 0.10 (10) Purified water 27.70 (11) Carboxyvinyl polymer 15.00 (1.0% by weight aqueous solution) (12) Potassium hydroxide (10.0% by weight aqueous solution) 1 0.00 (13) Flute bromelain 0.05 (14) Linden extract 0.25 (15) Purified water 3.00 (16) Perfume 0.10 Production method: (1) to (5) 70 ℃
And On the other hand, the water phase components (6) to (10) are mixed, heated and dissolved to 70 ° C. The oil phase is added to this aqueous phase for pre-emulsification, then (11) is added and stirred, and then (12) is added and stirred. After homogenizing the emulsified particles with a homomixer, cool, add (13) and (14) to (15) at 40 ° C, then add
Add (16) and mix evenly.

Example 12 Gel Mask / Face Cleanser (1) Myristic Acid 0.5000 (wt%) (2) Palmitic Acid 4.0000 (3) Stearic Acid 0.5000 (4) Behenyl Alcohol 2.0000 ( 5) Glyceryl monostearate 2.000 (6) Ethylene glycol distearate 1.0000 (7) Polyoxyethylene (60 E.O.) glyceryl 5.0000 Monoisostearate (8) Polyethylene glycol 5.0000 ( Average molecular weight 1,000) (9) Stearyl glycyrrhetinate 0.0500 (10) Glycerin 5.0000 (11) 1,3-Butylene glycol 5.0000 (12) N-lauroylmethyl-β-alanine sodium 5.0000 ( 13) Coconut oil fatty acid amidopropyl betaine solution 4. 0000 (14) Silicic anhydride 1.0000 (15) Purified water 40.0000 (16) Coconut oil fatty acid diethanolamide 2.0000 (17) Chitosan 0.0010 (18) Isomerized sugar mixture 0.0100 (19) Shinnaki Extract 0.6000 (20) Daidai extract 0.1000 (21) Sugarcane extract 0.1000 (22) Lemon extract 0.1000 (23) Bilberry extract 0.1000 (24) Sugar maple extract 0.1000 (25) Copper chlorophyllin sodium 0.0005 (26) Purified water 11.8185 (27) Eucalyptus oil 0.0500 (28) l-menthol 0.0500 (29) Perfume 0.2000 (30) Polyethylene powder 4.0000 ( 31) Crystalline cellulose 0.5000 (32) Talc 0.1000 (33) Corn starch 0.1000 (34) Argi Sodium acid salt 0.0100 (35) Calcium chloride 0.0100 Manufacturing method: The oil phase components (1) to (9) are mixed, heated and dissolved to give 75
℃. On the other hand, the water phase components (10) to (15) are mixed and dissolved to 75 ° C. The above oil phase was added thereto, mixed and stirred, cooled, and (16) to (26) and (27) to (29) were sequentially added and mixed at 60 ° C, and then (30) and premixed. (31) to (35) were added and dispersed. As the isomerized sugar mixture of (18), a commercially available product under the trade name of “Pentavitine” from Pentafarm was used.

Example 13 Hand Cream (1) Cetanol 4.00 (wt%) (2) Vaseline 2.00 (3) Liquid Paraffin 10.00 (4) Glyceryl Monostearate 1.50 (5) Polyoxyethylene (60 E.O.) glyceryl 2.50 isostearic acid ester (6) tocopherol acetate 0.25 (7) glycerin 20.00 (8) methyl paraoxybenzoate 0.10 (9) tomato extract 0.50 (10) Purified water 56.88 (11) Pineapple extract 0.02 (12) Bodaiju extract 0.25 (13) Purified water 2.00 Production method: Mix the oil phase components of (1) to (6), Melt to 75 ° C. On the other hand, (7) to (10) are mixed and dissolved, and the temperature is adjusted to 75 ° C.
Next, the oil phase component was added to the aqueous phase component, and the mixture was uniformly emulsified with a homomixer, cooled, and at 40 ° C. (11),
Dissolve (12) in (13) and add and mix.

Among Examples of the present invention described above, Examples 1 to 5 were evaluated for their effect on parakeratosis due to inflammation. In that case, in each Example, the blended plant protease or a plant extract containing the same or a plant extract having protease-like activity, and a hydroxycarboxylic acid or a plant extract containing the same are shown in Table 1, respectively. The substitutes were designated as Comparative Examples 1 to 5 and evaluated at the same time.

[0075]

[Table 1]

The evaluation was carried out by a use test in which 20 female panelists exhibiting rough skin symptoms due to skin inflammation were used as one group. That is, each of the groups was allowed to use each of the examples and comparative examples continuously in the blind twice a day for 2 months, and the degree of parakeratosis and skin condition before the start of the use test and after the end of the use test were compared. did. The degree of parakeratosis was measured by observing the presence or absence of nucleated cells under a microscope by collecting the stratum corneum of the skin surface by tape stripping, applying tissue staining, and using the average value of the incidence (score) of nucleated keratinocytes. expressed. The skin condition is
It was observed with a microscope, scored according to the evaluation criteria shown in Table 2, and expressed as an average value of 20 persons. The evaluation results are summarized in Table 3.

[0077]

[Table 2]

[0078]

[Table 3]

As is clear from Table 3, the incidence of nucleated keratinocytes was clearly reduced in all the groups used in the examples of the present invention, indicating that parakeratosis symptoms were improved. It had been. Also, the skin condition was improved to almost healthy condition. On the other hand, Comparative Example 1 containing only a plant protease, Comparative Example 2 containing only a salt of hydroxycarboxylic acid, an extract of a plant containing a plant protease and an extract of a plant having protease-like activity were prepared. Comparative Example 3 containing, Comparative Example 4 containing only a plant extract containing hydroxycarboxylic acids
Although a decrease in the incidence of nucleated keratinocytes was observed in each of the use groups, the degree thereof was smaller than that in each of the corresponding Example use groups, and an improvement tendency was observed in the skin condition. It was also insufficient in the use group.
Further, in the group using Comparative Example 5 which did not contain both the plant protease and the plant extract containing hydroxycarboxylic acids, no significant decrease in the incidence of nucleated keratinocytes was observed and the skin condition was not improved. It was

Next, Examples 1 to 13 of the present invention were subjected to a usage test by a female panelist exhibiting remarkable keratinization symptoms or dullness. At that time, in Examples 6 to 13, the plant extract containing the blended plant protease or the plant extract having protease-like activity, and the hydroxycarboxylic acid or the plant extract containing the same are shown in Tables 1 and 2, respectively. As shown in FIG. 4, the substitutes were used as Comparative Examples 6 to 13, and were subjected to a usage test together with the above-mentioned Comparative Examples 1 to 5. The use test was carried out by using 20 people as one group, and using each of the examples and the comparative examples in blind to each group, and observing the dry state of the skin, the degree of keratin thickening, the improvement of scales and dullness, and clarifying Table 5 shows the number of panelists that showed significant improvement.

[0081]

[Table 4]

[0082]

[Table 5]

As is clear from Table 5, in the groups used in the examples of the present invention, a good improvement was generally observed. The dry state was 45% or more, the keratin thickening was 50% or more, and the scale was 45% or more, 45 for dullness
A clear improvement was observed in more than 100% of the panelists. On the other hand, a plant protease or a plant extract containing the same or a plant extract having protease-like activity,
In each of the use groups of Comparative Example 1 to Comparative Example 4 and Comparative Example 6 to Comparative Example 11 containing only one of the hydroxycarboxylic acids and the plant extract containing the same, improvement of keratinization symptoms and dull skin. Although there was a tendency, the number of panelists who showed a clear improvement was significantly smaller than that in the corresponding groups used in Examples. Further, in the group using Comparative Example 12 in which the plant extract containing the hydroxycarboxylic acids was substituted with glycolic acid without containing the plant extract having protease-like activity, a considerably good improvement was observed for each symptom. Comparative Example 5 containing neither plant protease nor plant extract containing hydroxycarboxylic acids, and plant extract containing plant protease, plant extract having protease-like activity and hydroxycarboxylic acids. In the group of Comparative Example 13 in which all of the contained plant extracts were replaced with urea, almost no clear improvement in keratinization symptoms and skin dullness was observed.

In the above use test, no panelists complained of discomfort during use or skin irritative reaction in the use group of the present invention. In addition, in Examples 1 to 10 of the present invention, no change in the state of the preparation was observed when stored at 25 ° C for 6 months. On the other hand, in the group using Comparative Example 12, eight panelists complained of some discomfort during use.

[0085]

INDUSTRIAL APPLICABILITY As described in detail above, according to the present invention, abnormally generated and thickened keratin and keratin accumulated due to delayed detachment are removed, and psoriasis, ichthyosis vulgaris, palmoplantar keratosis,
Keratinization symptoms such as Dariere's disease, flies, chicken eyes, and Dry
It was possible to obtain a skin external preparation that can effectively improve skin, skin stains, dullness, skin roughening symptoms, etc., has good formulation stability, and is hypoallergenic to the skin.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/60 A61K 31/60 35/78 35/78 C D E H K R S U X 38/46 A61P 17/00 A61P 17/00 17/16 17/16 43/00 121 43/00 121 A61K 37/54 (72) Inventor Satoshi Maeda 112-1 Nogami, Okada-cho, Yokaichi-shi, Shiga Prefecture Noevir Shiga Research Institute (72) Inventor Ritsuko Koshimizu 112-1 Nogami, Okada-cho, Yokaichi-shi, Shiga Prefecture Noevir Shiga Research Institute Co., Ltd. (72) Masumi Takei 112-1 Nogami, Okada-cho, Yokaichi-shi, Shiga Prefecture Laboratory F-term (reference) 4C083 AA082 AA111 AA112 AA122 AB032 AB172 AB332 AB432 AC012 AC022 AC072 AC102 AC122 AC242 AC301 AC302 AC422 AC432 AC442 AC471 AC482 AC582 AC642 AC662 AC712 AC782 AC9 32 AD022 AD042 AD092 AD152 AD192 AD242 AD262 AD282 AD302 AD322 AD352 AD471 AD472 AD512 AD532 AD662 CC02 CC03 CC04 CC05 CC07 CC22 CC23 DD31 DD33 DD41 EE06 EE07 EE10 EE12 4C084 AA02 BA44 DC02 MA02 MA02 MA02 A02 MA02 A02 MA02 NA02 ZA891 NA14 ZA89 4C088 AB12 AB19 AB34 AB43 AB44 AB48 AB51 AB62 AB78 AB84 AC03 AC04 AC05 AC06 AC11 AC12 AC13 BA08 CA03 MA07 MA08 MA63 NA06 NA07 NA14 ZA89 4C206 AA01 AA02 DA07 DA36 MA02 MA04 MA11 MA83 NA06 NA07 NA14 ZA89

Claims (5)

[Claims] 1. A skin external preparation comprising the following components (A) and (B). (A) One or two selected from the group consisting of plant proteases, plant extracts containing them, and plant extracts having protease-like activity
More than seeds. (B) One or more selected from the group consisting of hydroxycarboxylic acids and salts and derivatives thereof, and plant extracts containing one or more of the hydroxycarboxylic acids and salts and derivatives. 2. The external preparation for skin according to claim 1, wherein the plant protease is selected from papain, ficin and bromelain. 3. A plant containing a plant protease and a plant extract having a protease-like activity are ficus ( Ficus carica L.) and kiwi ( Actinidia chinensis P
lanch.), plants belonging to the genus Tilia , germinated maize ( Zeamays L.), pineapple ( Bromelia )
ceae ), papaya ( Caricapapaya L.),
Cucumis melo L. and yams ( Diosc
orea japonica Thunb.), the external preparation for skin according to claim 1 or 2, which is selected from each extract. 4. The hydroxycarboxylic acid and salts and derivatives thereof are selected from lactic acid, citric acid, succinic acid, tartaric acid, malic acid, salicylic acid and salts and derivatives thereof. Item 4. The external skin preparation according to Item 3. 5. A plant extract containing one or more of hydroxycarboxylic acid and salts and derivatives thereof is apricot ( Pr.
unus armeniaca L. var. ansu Maxim.), Knotweed ( Po
lygonum cuspidatum Sieb. et Zucc.) and its variants and related species, plants belonging to the genus Strawberry ( Fragaria ), plum ( Prunus mume Sieb. et Zucc.), raspberries ( Rubus )
Acer saccharum Mars, a plant belonging to the genus
h.), sugar cane ( Saccharum officinarum L.), Sanshuyu ( Cornus officinalis Sieb. et Zucc.), Shikunushi ( Quisqualis indica L. var. villosa Clarke),
Indian gentleman (Quisqualis indica L.), Vaccinium (Va
A plant belonging to the genus ccinium, Schisan
dra chinensis Baill.), tomato ( Solanum lycopersic
um L.), jujube ( Zizyphus vulgaris Lam. var. inerm
is Bunge), loquat ( Eriobotrya japonica Lindl.), bokeh ( Chaenomeles lagenaria Koids.), bokeh ( Chae )
nomeles japonica Lindl.), Yodoboke ( Chaenomeles s )
peciosa Nakai), Karin ( Chaenomeles sinensis Koen)
ne), plant belonging to the genus Citrus , longan ( Euphoria longana Lam.), apple ( Malus p)
umila Miller var. domestica Schneider) and waringo ( Malus pumila Miller var. dulcissima Koidz.) extracts, the external preparation for skin according to claims 1 to 4 characterized by the above-mentioned.