JP2003201214A - Matrix metalloprotease activity inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a matrix metalloprotease (MMPs) activity inhibitor which has an excellent antagonistic action against the activity of the MMPs giving a large effect to the ageing of the skin and can prevent the degradation of skin extracellular matrix components (for example, elastin, laminin, proteoglycan, basement membrane components, collagen) deeply related to the ageing of the skin to prevent and improve the ageing of the skin. <P>SOLUTION: This matrix metalloprotease (MMPs) activity inhibitor contains one or more plants selected from Woodfordia floribunda, Persea americana, Rhubarb sp., Cassia angustifolia, Garcinia mangostana, Cinamomum cassia, Tamaindus indica, Bergenia ciliata, luehea divaricata, luehea grandiflora, luehea ochrophylla, luehea paniculata, luehea rufescens, Arctium lappa, Artium minus, Anemopaegma arvense, Anemopaegma glaucum, Erythroxylum vaccinifolium, Margaritaria nobilis, and Pouteria obtusifolia, or a solvent extract thereof. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a matrix metalloprotease activity inhibitor containing a specific plant or a solvent extract thereof. More specifically, it has an excellent antagonistic effect on the activity of specific matrix metalloproteinases (MMPs) that have a great effect on skin aging, and effectively prevents, prevents, and improves skin aging. The present invention relates to an MMPs activity inhibitor capable of INDUSTRIAL APPLICABILITY The present invention can be suitably used for basic cosmetics, makeup cosmetics, hair cosmetics, bath agents and the like.

[0002]

BACKGROUND OF THE INVENTION Human skin is roughly divided into three layers, epidermis, dermis and subcutaneous tissue, and the epidermis and dermis are in contact with each other via a basement membrane.

In the basement membrane, basal cells intolerate and repeatedly divide, and the divided basal cells are sequentially pushed upward to form the stratum corneum, which is the uppermost layer of the epidermis. The stratum corneum is extremely deeply related to the cosmetic properties of the skin,
The effect of the basement membrane on the skin is also great. Basement membrane is a type of extracellular matrix (described later), type IV collagen,
Including proteoglycan, laminin, fibronectin, etc.

The dermis consists of connective tissue, and the extracellular space is mainly composed of extracellular matrix (ECM).
It is filled with a macromolecular network called x). The extracellular matrix (ECM) is composed of fibrous proteins (collagen, elastin, etc.) and cell adhesion proteins (glycosaminoglycan, proteoglycan, fibronectin, laminin, etc.), and this structure allows the dermis to have elasticity and elasticity of the skin. It has a great influence on.

It has been known that ultraviolet rays and a decrease in female hormones observed during menopause are greatly involved in changes associated with aging of the skin, that is, wrinkles, dullness, loss of texture, and decrease in elasticity. There is. When these changes are viewed microscopically, extracellular matrix components (ECM) such as collagen and elastin in the dermis are decreased / denatured, and further, basement membrane damage and epidermal thickening occur.

[0006] In recent years, research has progressed, and as factors inducing these changes, matrix metalloprotease (M
The involvement of MPs) is pointed out. MMPs are a generic name for a group of proteases whose extracellular matrix proteins are the main substrates. Many types of MMPs are known, and although they have common structural and functional characteristics, they have different substrate proteins (Miyazaki Ka, et al., “Biochemistry”, Vol. 68). No. 12, pp.1791-1807 (1
996)).

MMPs are usually classified into gelatinase group, stromlysin group, collagenase group, and others (matrilysin and the like) in terms of structure and function.

The gelatinase group includes MMP-2 and MMP.
-9 etc. are included. These MMP-2 and 9 are known as enzymes that decompose type IV collagen and laminin which are basement membrane components, and elastin which is a dermal matrix component.

In the stromlysin group, MMP-3, M
MP-10 etc. are included. These MMP-3 and 10 are
It is known as an enzyme that decomposes proteoglycan, which is a basement membrane component, type IV collagen, laminin, and other fibronectin.

The collagenase group includes MMP-1 (interstitial collagenase), MMP-8, MMP-13 and the like. Among them, MMP-1 is known as an enzyme that decomposes type I and III collagen, which are the main constituents of the dermal matrix, and proteoglycan, which is a basement membrane component. MMP-8 and MMP-13 also have the action of degrading type I collagen and the like.

Further, the expression of each of these enzymes is greatly increased by irradiation of ultraviolet rays, which is one of the causes of the degeneration and modification of extracellular matrix (ECM) by ultraviolet rays, which is one of the major factors such as the formation of skin wrinkles. (V. Koivukangas et al., "Acta Derm Venereol")
(Stockh), 74, 279-282 (1994); Gary J. Fisher et al.,
"Nature", 379 (25), 335 (1996); Gary J. Fisher et a
l., "The New England Journal of Medicine", 337 (2
0), 1419 (1997)). In addition to UV irradiation, a drastic decrease and deficiency of female hormones during menopause triggers
It was revealed that an increase in MMP-2 and MMP-9 in the skin occurs, which is a cause of skin wrinkles, sagging, etc., as in the case of ultraviolet irradiation (Japanese Patent Application No. 2001-5).
0839, N. Ochiai et al., "Jpn. J. Dermat.
ol. ", 111 (3), 532 (Abs.) (2001)).
Inhibition of s activity protects various extracellular matrices,
It is extremely important in preventing skin aging.

Many conventional anti-aging agents have a mechanism of activating fibroblasts and increasing collagen production, but extracellular matrix (ECM)
What is focused on the inhibition of the activity of each of the MMPs on the above is limited (JP 2001-139466 A, JP 2
001-172157, JP 2001-19231
6 gazette, Unexamined-Japanese-Patent No. 2001-192317).

Therefore, the present invention can surely inhibit the activity of MMPs closely related to skin aging,
It is an object of the present invention to provide a highly safe MMPs activity inhibitor which is excellent in preventing / preventing and improving skin aging and highly safe.

[0014]

In order to solve the above-mentioned problems, the inventors of the present invention have widely used various Ms for various substances.
As a result of examining the MPs activity inhibitory action, it was found that a specific plant or its extract has an excellent MMPs activity inhibitory action, and the present invention has been completed.

That is, the present invention relates to Woodfordia
Florforda (Woodfordia floribunda Salisb.), Avocado (Persea americana Mill.), Rheum
sp.), Hosobasenna (Cassia angustifolia Vahl),
Mangostin (Garcinia mangostana L.), Cassia (Ci
nnamomum cassia Bl.), Tamarind (Tamarindus indi)
ca L.), Bergenia ciliata (H
aw.) Sternb.), Luehea div
aricata Mart. et Zucc.), Luehea grandiflora Mart. et Zucc., Luehea ochrophylla Mart., Luehea paniculataMart. et Zuc
c.), Luehea rufescens A.
St. Hil.), Burdock (Arctium lappa L.), Arctium minus, Anemopaegma arvense (Vell.), Anemopaegma glaucum Mrt. Ex D
C.), Erythroxylam Baxinofolium (Erythr
oxylum vaccinifolium Mart.), Margaritaria nobilis L. f., and Pouteria obtusifolia Baehn
a gelatinase group comprising one or more plants selected from i) or a solvent extract thereof,
Inhibits the activity of matrix metalloproteases (MMPs) belonging to any of the stromlysin groups,
The present invention relates to MMPs activity inhibitors.

The present invention also relates to the above MMPs activity inhibitor, which is any one of an elastin degradation inhibitor, a laminin degradation inhibitor, a basement membrane degradation inhibitor, and a proteoglycan degradation inhibitor.

The present invention also relates to Woodfordia floribunda Salisb., Avocado (Persea americana Mill.), Rhubarb (Rheum s).
p.), Hosobasena (Cassia angustifolia Vahl), Mangosteen (Garcinia mangostana L.), Cassia (Cinn
amomum cassia Bl.), Tamarind (Tamarindus indica)
L.), Luehea divaricata Ma
rt. et Zucc.), Luhea Grandiflora (Luehea)
grandiflora Mart. et Zucc.), Luhea ochrophylla Mart., Luehea paniculata Mart. et Zucc., Luehea rufescens A. St. Hil.,
Burdock (Arctium lappa L.), Arctium Minus (Arctium minus), Anemopa Egma Abense (Ane)
mopaegma arvense (Vell.)), Anemopaegma glaucum Mrt. ex DC., Erythroxylum vacciniforium
folium Mart.), Margaritalia Nobilis (Margarit)
aria nobilis L. f.) and one or more plants selected from Pouteria obtusifolia Baehni, or a solvent extract thereof, which is a matrix metalloprotease belonging to the collagenase group ( Inhibiting the activity of MMPs),
The present invention relates to MMPs activity inhibitors.

The present invention also relates to the above MMPs activity inhibitor, which is a collagen degradation inhibitor.

[0019]

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

Wood Fordia used in the present invention
Florifunda (Woodfordia floribunda Salisb.)
Lythraceae genus Wood Fordia
fordia) is a plant species belonging to. It is cultivated as a tropical flowering tree, and red dye is collected from the flowers. Dried flowers are used as a tonic, flowers and roots are used for medicinal purposes such as diarrhea and irregular menstruation.

Avocado (Persea americana Mill.)
Is a plant species that belongs to the Lauraceae genus Avocado (Persea). The pulp is rich in fat, high in protein and vitamins, and is used for raw eating. The leaf is used as a diuretic.

Rheum sp.
onaceae) is a group of plants belonging to the genus Rheum.
As a medicinal plant, about 50 species are distributed in Asia,
Several rhizomes are used as rhubarb.

[Hosobasenna (Cassia angustifolia Vah
l) is a plant species belonging to the family Leguminosae (Fabaceae) belonging to the genus Cassia. The leaves are called senna leaves and used as a laxative for constipation. Senna leaves include the anthraquinoids sennosides A, B, C, D, chrysophanol, flavonoids, and the like.

[0024] Mangosteen (Garcinia mangostana L.)
Is a plant species belonging to the genus Garttinia (Garcinia) of the Hypericumaceae family (Guttiferae (Hypericaceae)). An evergreen fruit tree cultivated in a tropical region, the skin part of which contains tannin and a yellow pigment (mangosteen). Dry bark also becomes a black dye.

Cassia (Cinnamomum cassia Bl.) Is a plant species belonging to the genus Cinnamomum of the camphoraceae family.
Also known as Tonkin Nikkei (Tokyo meat katsura) and Kay (Katsura).
The skin of branches and trunks is called cinnamon bark and is medicinal. The branches and leaves are steam-distilled to produce cassia oil (cinnamon oil), which is medicated.
Used as a fragrance.

Tamarind (Tamarindus indica L.) is
It is a plant species belonging to the genus Tamarindus of the legume family. The pulp has acidity and sweetness, and is medicinal (promoting appetite, laxative)
Used for.

[0027] Bergenia ciliata
(Haw.) Sternb.) Is a family of Saxifragaceae.
It is a plant species belonging to the genus Himalaya Yukinoshita (Bergenia). It is a root-root plant with extremely high cold resistance.

Luhea divaric
ata Mart. et Zucc.), Ruhea Grandiflora (Luehea grandiflora Mart. et Zucc.), Ruhea
Luechea ochrophylla Mart., Luehea paniculata Mart. Et Zuc
c.), Luehea rufescens A.
St. Hil.) Is a plant species belonging to the genus Luhea of the family Tiliaceae.

Both burdock (Arctium lappa L.) and Architium minus (Arctium minus) are Asteraceae (C
ompositae (= Asteraceae)) It is a plant species belonging to the genus Burdock (Arctium).

Anemopaegm (Anemopaegm)
a arvense (Vell.)), Anemopaegma Graucum (A
nemopaegma glaucum Mrt. ex DC.) are all of the genus Anignopea (Bignoniaceae).
aegma) is a plant species that belongs to.

Erythroxylum vaccinifolium Mart. Is a plant species belonging to the genus Erythroxylum of the family Erythroxylaceae.

Margaritaria nobilis
nobilis L. f.) is a Euphorbiaceae (Euphorbiacea)
e) A plant species belonging to the genus Margaritaria.

Pouteria Pouteria
obtusifolia Baehni) is a family of Sapotaceae.
It is a plant species that belongs to the genus Pouteria.

The above-mentioned plants used in the present invention are known to have various pharmacological activities.
It has not been known so far that it has an activity of inhibiting MMPs activity, and this time, the present inventors have first found this time.

Each of the plants used in the present invention may be used as a raw or dried plant, but it is preferably used as a dry powder or a solvent extract from the viewpoints of usability and formulation.

The above-mentioned plant can be used as leaves, branches,
Any part of each plant such as flowers, roots, fruits, peels, seeds and bark can be used, but the following parts are particularly preferably used.

Wood Fordia Floribunda (W. f
loribunda), it is particularly preferable to use leaves and flowers,
Other sites can also be used.

For avocado (P. americana) it is particularly preferred to use the bark, but other sites can also be used.

It is particularly preferable to use roots in Rheum sp., But other sites can also be used.

In the case of C. angustifolia, it is particularly preferable to use leaves, but other parts can also be used.

For mangosteen (G. mangostana), it is particularly preferable to use the pericarp or bark, but other sites can also be used.

In C. cassia, it is particularly preferable to use fruits, but other parts can also be used.

Bark is particularly preferred for T. indica, although other sites can be used.

It is particularly preferred to use rhizomes in B. ciliata, but other sites can also be used.

L. divaricat
a), Ruhea Grandiflora (L. grandiflor)
a), ruehair ocrophylla (L. ochrophylla), ruehair paniculata (L. paniculata), ruehair
For L. rufescens it is particularly preferred to use the bark, but other sites can also be used.

For burdock (A. lappa) and Arctium minus (A. minus), it is particularly preferable to use leaves or roots, but other regions can also be used.

Anemopa Egma Abense (A. arvens
e), it is particularly preferable to use bark in A. glaucum, but other sites can also be used.

For E. vaccinifolium it is particularly preferred to use the bark, but other sites can be used.

Margaritalia nobilis
Then, it is particularly preferable to use the bark, but other sites can be used.

P. obtus
For ifolia) it is particularly preferred to use the bark, but other sites can also be used.

The extract of each of the above plants can be obtained by a conventional method, for example, it can be obtained by immersing or heating and refluxing each of the above plants with an extraction solvent, and then filtering and concentrating. As the extraction solvent, any solvent that is usually used for extraction can be used, and examples thereof include water, alcohols such as methanol, ethanol, propylene glycol, 1,3-butylene glycol, and glycerin, hydroalcohols, and chloroform. Organic solvents such as dichloroethane, carbon tetrachloride, acetone, ethyl acetate and hexane can be used alone or in combination. The extract obtained by extraction with the above solvent is used as it is, or the concentrated extract is adsorbed by an adsorption method, for example, one obtained by removing impurities using an ion exchange resin, or a column of a porous polymer (for example, Amberlite XAD-2). It is possible to use a product obtained by eluting with methanol or ethanol after the reaction and concentrating. Also the partitioning method, eg water /
An extract or the like extracted with ethyl acetate is also used.

The above-mentioned plants or their extracts are highly safe, have an excellent MMPs activity inhibitory action, and have an excellent anti-aging action, especially an anti-skin aging action.

In the present invention, in particular, W. floribunda and Avocado (P. american)
a), Rheum sp., C. angus
tifolia), mangostana (G. mangostana), cassia (C. cassia), tamarind (T. indica), bergenia sirita (B. ciliata.), ruehair divaricata (L. divaricata), ruehair grandiflora (L.
grandiflora), Lue ochrophyra (L. ochrophy)
lla), Lue paniculata, L. rufescens, Burdock (A. l)
appa), Arctium Minus (A. minus), Anemopa Eggma Arvense (A. arvense), Anemopa Eggma Graucum (A. glaucum), Erythroxylum Baxinofolium (E. vaccinifolium), Margaritalia nobilis (M. nobilis), and one or more plants selected from P. obtusifolia (P. obtusifolia), or solvent extracts thereof, for all MMPs belonging to either the gelatinase group or the stromlysin group. Excellent MMPs antagonism,
It has an activity-inhibiting effect.

Examples of the activity inhibitor of MMPs belonging to the gelatinase group include application as an elastin degradation inhibitor, a laminin degradation inhibitor, and a basement membrane degradation inhibitor.

As an activity inhibitor of MMPs belonging to the stromlysin group, application as a proteoglycan degradation inhibitor or laminin degradation inhibitor can be exemplified.

In the present invention, among the above-mentioned plants, plants other than B. ciliata, that is, Woodfordia floribund (W. floribund)
a), avocado (P. americana), rhubarb (Rheum s)
p.), Hosobasenna (C. angustifolia), Mangosteen (G. mangostana), Cassia (C. cassia), Tamarind (T. indica), Ruhea hair divaricata (L. divari)
cata), Ruhea Grandiflora (L. grandiflor)
a), ruehair ocrophylla (L. ochrophylla), ruehair paniculata (L. paniculata), ruehair
L. rufescens, Burdock (A. lappa),
A. minus, A. arvense, A. glaucum, E. vaccinifolium, Margaritalia nobilis , And one or more kinds of plants selected from P. obtusifolia, or a solvent extract thereof, can further effectively inhibit the activity of MMPs belonging to the collagenase group.

As an activity inhibitor of MMPs belonging to the collagenase group, application as a collagen degradation inhibitor is exemplified.

Further, any of the above MMPs activity inhibitors of the present invention can be applied as an anti-wrinkle agent for the purpose of preventing / preventing and improving wrinkles.

In the present invention, the "inhibitor of MMPs activity" means matrix metalloprotease (MMPs).
It broadly means a preparation having an antagonistic effect on the activity.

The matrix metalloprotease inhibitor of the present invention is preferably used as an anti-aging cosmetic composition, a skin external preparation, etc. In that case, the compounding amount of each plant or its extract is The dry mass (mass of solid content) is preferably 0.0001 to 20 mass%, and particularly 0.0001 to 10 mass%. If it is less than 0.0001% by mass, the effect of the present invention is difficult to be sufficiently exerted, while
Even if it is blended in an amount of more than 20% by mass, no significant improvement in the effect is recognized, and formulation becomes difficult, which is not preferable.

When the MMPs activity inhibitor of the present invention is used, for example, in an anti-aging cosmetic composition, it is usually used in an external preparation such as cosmetics and pharmaceuticals in addition to the above-mentioned essential components, within a range not impairing the effects of the present invention. Ingredients such as whitening agents, moisturizers, antioxidants, oily ingredients, UV absorbers, surfactants, thickeners, alcohols, powder ingredients, coloring agents, aqueous ingredients, water, various skin nutrition agents, etc. It can be appropriately blended if necessary.

Further, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extraction Substance, glabridin, hot water extract of karin fruit, various herbal medicines, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbyl phosphate, ascorbyl glucoside, arbutin, kojic acid, etc. Other whitening agents, sugars such as glucose, fructose, mannose, sucrose, trehalose, and vitamin A derivatives such as retinoic acid, retinol, retinol acetate, retinol palmitate, and the like can be appropriately added.

The dosage form of the present invention is not particularly limited, and it may be a solution system, a solubilization system, an emulsion system, a powder dispersion system, a water system.
Any formulation such as oil bilayer system, water-oil-powder trilayer system, ointment, gel, aerosol and the like can be applied.

Further, its use form is also arbitrary, and for example, it is used for makeup cosmetics, hair cosmetics, fragrance cosmetics, bath agents, etc. in addition to facial cosmetics and foundations such as lotions, emulsions, creams and packs. However, it goes without saying that the present invention is not limited to these examples.

[0065]

EXAMPLES Next, the present invention will be described in more detail by way of examples, but the technical scope of the present invention is not limited to these examples.

Prior to the examples, the test method and evaluation method for the MMP-9, MMP-3 and MMP-1 activity inhibitory effect of each plant extract used in the present invention will be described.

[Test Method and Evaluation Method] 1. Sample preparation

(1) Plant Extract As shown in Table 1, each plant was immersed in methanol at room temperature for 1 week to obtain an extract. This extract was concentrated to obtain each plant extract (methanol extract).

[0069]

[Table 1]

The above plant extract was dissolved in dimethyl sulfoxide (DMSO) to a concentration of 2% by mass to obtain a plant extract containing solution.

Each of the solutions containing the plant extract was subjected to a measurement buffer (0.4M NaCl, 10 mM CaCl ₂
0.1 M Tris, pH 7.4, containing) and Table 2
The concentration was adjusted as shown in ~ 5, and this was used as a sample solution, and the following experiment was conducted.

2. MMPs activity inhibitory effect test (1) MMP-9 activity inhibition rate The activity inhibition rate was measured using MMP-9 as an enzyme belonging to the gelatinase group. The measurement was performed as follows.

That is, S containing 0.2% by mass of gelatin
Prepare a DS-polyacrylamide gel (10% T),
A fixed amount of human cell-derived MMP-9 solution was applied to all lanes and electrophoresed. The gel after electrophoresis was washed with 2.5% by mass of "Triton X-100", and further incubated with a buffer solution (0.01 mM ZnSO ₄ , 5 mM Ca).
S well with Cl ₂ (50 mM Tris, pH 8.0)
The DS was removed. Cut the gel into strips,
The sample was immersed in an incubation buffer containing a predetermined concentration and incubated overnight at 37 ° C.

After the incubation, the gel was stained with Coomassie Brilliant Blue and the thickness of the band that appeared after decolorization was measured with an image analyzer (Bio-Rad "Fluor-S").
Multi Imager ”).

Then, the reduction value of the band in the system containing the plant extract (the above sample solution) with respect to the value of the band in the reaction system containing no plant extract (control; DMSO) was determined to obtain the MMP-9 activity. The inhibition rate (%) was calculated. The results are shown in Tables 2-3. In addition, as a reference example, the same test as described above was performed for ethylenediaminetetraacetic acid (EDTA), which is a substance well known to have an activity of inhibiting MMPs activity. The results are also shown in Table 3.

(2) MMP-1,3 For the measurement, a measuring kit for stromelysin-1, type I collagenase, manufactured by Yagai was used. Human cell-derived enzymes were used as MMPs. That is, MMP-3 was used as an enzyme belonging to the stromlysin group, and MMP-1 was used as an enzyme belonging to the collagenase group (all manufactured by Yagami).

50 μl of the above sample solution, 100 μl of enzyme solution containing a fixed amount of enzyme (0.4 unit / ml), and 50 μl of fluorescent labeled substrate solution (1 mg / ml) were combined, and fixed time (2-4 hours), After incubating at 42 ° C, after stopping the enzymatic reaction by adding an ethanol solution, the unreacted substrate was precipitated by centrifugation, and the fluorescence intensity of the decomposed substrate remaining in the supernatant was measured to determine the decomposition rate of the substrate. It was

Then, from the ratio of the decomposition rate in the system containing the plant extract (the above sample solution) to the substrate decomposition rate in the reaction system not containing the plant extract (control; DMSO), each of the plant extracts was determined. The enzyme activity inhibition rate was determined. The results are shown in Tables 4 and 5.

Further, as a reference example, the same test as above was carried out on ethylenediaminetetraacetic acid (EDTA), which is a substance well known for its inhibitory action on MMPs activity.
The results are also shown in Tables 4 and 5.

[0080]

[Table 2]

[0081]

[Table 3]

[0082]

[Table 4]

[0083]

[Table 5]

As is clear from Tables 2 to 5, MMP-9, MMP-3 and MM of each plant extract used in the present invention.
P-1 activity inhibitory effect is the effect of EDTA MMP-9, MMP
-3, which was extremely superior to the effect of inhibiting MMP-1 activity. Therefore, the aging of the skin such as wrinkles and sagging can be effectively prevented / prevented / improved by using these plants or extracts thereof.

Examples of the formulation of the present invention will be described below as examples.

(Example 1) Cream (composition component) (mass%) (1) Stearic acid 5.0 (2) Stearyl alcohol 4.0 (3) Isopropyl myristate 18.0 (4) Glycerin monostearin Acid ester 3.0 (5) Propylene glycol 10.0 (6) Woodfordia floribunda extract 0.01 (50% 1,3-butylene glycol extract, concentration 2.01%) (7) Potassium potassium 0.2 (8) Sulfurous acid Sodium hydrogen 0.01 (9) Preservative Suitable amount (10) Perfume Suitable amount (11) Ion-exchanged water Residual (manufacturing method) (5) to (7) are dissolved in (11) and heated to 70 ° C. Keep (water phase). On the other hand, (1) to (4),
(8) to (10) are mixed, heated and melted and maintained at 70 ° C (oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is kept for a while to cause the reaction. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

(Example 2) Cream (composition component) (mass%) (1) Stearic acid 2.0 (2) Stearyl alcohol 7.0 (3) Hydrogenated lanolin 2.0 (4) Squalane 5. 0 (5) 2-octyldodecyl alcohol 6.0 (6) polyoxyethylene (25 mol) cetyl alcohol ether 3.0 (7) glycerin monostearate 2.0 (8) propylene glycol 5.0 (9) Garcinia mangostana (bark) extract 0.05 (Ethanol extraction. Solid content) (10) Sodium hydrogen sulfite 0.03 (11) Ethylparaben 0.3 (12) Perfume proper amount (13) Ion-exchanged water residue (production method) ) Add (8) to (13), heat and keep at 70 ° C. (aqueous phase). On the other hand, (1) to (7), (9) to (12)
Are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring.

(Example 3) Cream (composition component) (mass%) (1) Solid paraffin 5.0 (2) Beeswax 10.0 (3) Vaseline 15.0 (4) Liquid paraffin 41.0 ( 5) Glycerin monostearate 2.0 (6) Polyoxyethylene (20 mol) sorbitan monolaurate 2.0 (7) Soap powder 0.1 (8) Borax 0.2 (9) Rheum sp. Extraction Substance (acetone extraction, solid content) 0.05 (10) Cassia angustifolia extract 0.05 (ethanol extract, concentration 5.0%) (11) sodium bisulfite 0.03 (12) ethylparaben 0.3 (13) Fragrance Suitable amount (14) Ion-exchanged water (7) and (8) are added to the residue (production method) (14) and heated to 7
Keep at 0 ° C (aqueous phase). On the other hand, (1)-(6), (9)-
(14) is mixed, melted by heating, and maintained at 70 ° C (oil phase).
The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After the reaction is completed, the mixture is uniformly emulsified with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

Example 4 Emulsion (composition component) (mass%) (1) Stearic acid 2.5 (2) Cetyl alcohol 1.5 (3) Vaseline 5.0 (4) Liquid paraffin 10.0 (5) Polyoxyethylene (10 mol) monooleate 2.0 (6) Polyethylene glycol 1500 3.0 (7) Triethanolamine 1.0 (8) Carboxyvinyl polymer 0.05 (“Carbopol 941”) , BFGoodrich) (9) Garcinia mangostana (pericarp) extract 0.01 (ethyl acetate extraction, solid content) (10) Sodium bisulfite 0.01 (11) Ethylparaben 0.3 (12) Perfume proper amount ( 13) Ion-exchanged water Residue (production method) Dissolve (8) in a small amount of (13) (Phase A).
On the other hand, (6) and (7) were added to the remaining (13), which was heated and melted and maintained at 70 ° C. (aqueous phase). (1)-(5), (9)
~ (12) are mixed, melted by heating and kept at 70 ° C (oil phase). The oil phase is added to the aqueous phase, preliminary emulsification is performed, phase A is added, and the mixture is uniformly emulsified with a homomixer. After emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

(Example 5) Emulsion (composition component) (mass%) (1) Microcrystalline wax 1.0 (2) Beeswax 2.0 (3) Lanolin 20.0 (4) Liquid paraffin 10.0 (5) Squalane 5.0 (6) Sorbitan sesquioleate 4.0 (7) Polyoxyethylene (20 mol) sorbitan monooleate 1.0 (8) Propylene glycol 7.0 (9) Cinnamomum cassia extraction Substance (acetone extraction. Solid content) 1.0 (10) Sodium bisulfite 0.01 (11) Ethylparaben 0.3 (12) Perfume proper amount (13) Ion-exchanged water Residue (production method) (13) ( 8) is added, heated and kept at 70 ° C. (aqueous phase). On the other hand, (1) to (7), (9) to (12)
Are mixed, heated and melted and maintained at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added to this, and the mixture is uniformly emulsified with a homomixer. After emulsification, mix well at 30 ℃
Cool down.

(Example 6) Jelly (composition component) (mass%) (1) 95% ethyl alcohol 10.0 (2) dipropylene glycol 15.0 (3) polyoxyethylene (50 mol) oleyl alcohol Ether 2.0 (4) Carboxyvinyl polymer 1.0 (“Carbopol 940”, BFGoodrich) (5) Caustic soda 0.15 (6) L-arginine 0.1 (7) Tamarindus indica extract 7.0 ( 50% ethanol extract, concentration 2.01%) (8) 2-hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 (9) ethylenediaminetetraacetate.3Na.2 water 0.05 (10) methylparaben 0.2 (11) ) Fragrance A suitable amount (12) Ion-exchanged water Dissolve (4) uniformly in the residue (production method) (12) (aqueous phase).
On the other hand, (7) and (3) are dissolved in (1) and this is added to the aqueous phase. Next, after adding (2) and (8) to (11) here, it is neutralized and thickened with (5) and (6).

Example 7 Beauty Serum (Composition) (Mass%) (Phase A) Ethyl Alcohol (95%) 10.0 Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Bergenia ciliata extract (methanol extraction, solid content) 1.5 Methylparaben 0.15 (Phase B) Potassium hydroxide 0.1 (Phase C) glycerin 5.0 Dipropylene glycol 10.0 Sodium hydrogen sulfite 0. 03 Carboxyvinyl polymer 0.2 (“Carbopol 940”, BFGoodrich) Purified water Residue (production method) Phase A and C were uniformly dissolved, and A was added to phase C
Add phase and solubilize. Then, after adding phase B, it is filled in a container.

Example 8 Pack (composition component) (mass%) (A phase) dipropylene glycol 5.0 polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) Garcinia mangostana (bark) ) Extract (methanol extraction. Solid content) 0.01 Olive oil 5.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Perfume 0.2 (Phase C) Sodium hydrogen sulfite 0.03 Polyvinyl alcohol (saponification degree 90, polymerization) 2,000) 13.0 Ethanol 7.0 Purified water Residual (production method) Dissolve Phases A, B, and C evenly,
Phase B is added to the phase to solubilize it. This is then added to phase C and then filled into a container.

(Example 9) Solid foundation (composition) (mass%) (1) Talc 43.1 (2) Kaolin 15.0 (3) Sericite 10.0 (4) Zinc white 7.0 (5) Titanium dioxide 3.8 (6) Yellow iron oxide 2.9 (7) Black iron oxide 0.2 (8) Squalane 8.0 (9) Isostearic acid 4.0 (10) POE sorbitan monooleate 3 0.0 (11) Isocetyl octoate 2.0 (12) Persea americana extract (ethanol extract, concentration 1.5%) 1.0 (13) Preservative suitable amount (14) Perfume suitable amount (production method) (1) to The powder component (7) is thoroughly mixed with a blender, and the oil component (8) to (11), (1
After adding 2), (13) and (14) and thoroughly kneading, the mixture is filled into a container and molded.

(Example 10) Emulsion type foundation (cream type) (composition component) (mass%) (powder part) titanium dioxide 10.3 sericite 5.4 kaolin 3.0 yellow iron oxide 0.8 Red iron oxide 0.3 Black iron oxide 0.2 (Oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (Aqueous phase) Purified water 51.0 1,3- Butylene glycol 4.5 Garcinia mangostana (bark) extract 1.5 (ethanol extract, concentration 1.05%) sorbitan sesquioleate 3.0 preservative proper amount perfume appropriate amount (production method) After heating and stirring the aqueous phase, it is sufficient Then, the powder portion which has been mixed and pulverized is added to the mixture and homomixed. Further, the heated and mixed oil phase is added and treated with a homomixer, and then the fragrance is added with stirring and cooled to room temperature.

(Example 11) Cream (composition component) (mass%) (1) Stearic acid 5.0 (2) Stearyl alcohol 4.0 (3) Isopropyl myristate 18.0 (4) Glycerin monostearin Acid ester 3.0 (5) Propylene glycol 10.0 (6) Luehea divaricata extract 0.01 (50% 1,3-butylene glycol extract, concentration 2.0%) (7) Caustic potassium 0.2 (8) Sulfurous acid Sodium hydrogen 0.01 (9) Preservative Suitable amount (10) Perfume Suitable amount (11) Ion-exchanged water Residual (manufacturing method) (5) to (7) are dissolved in (11) and heated to 70 ° C. Keep (water phase). On the other hand, (1) to (4),
(8) to (10) are mixed, heated and melted and maintained at 70 ° C (oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is kept for a while to cause the reaction. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

(Example 12) Cream (composite component) (mass%) (1) Stearic acid 2.0 (2) Stearyl alcohol 7.0 (3) Hydrogenated lanolin 2.0 (4) Squalane 5. 0 (5) 2-octyldodecyl alcohol 6.0 (6) polyoxyethylene (25 mol) cetyl alcohol ether 3.0 (7) glycerin monostearate 2.0 (8) propylene glycol 5.0 (9) Luehea grandiflora extract (ethanol extraction, solid content) 0.05 (10) Sodium bisulfite 0.03 (11) Ethylparaben 0.3 (12) Perfume proper amount (13) Ion-exchanged water residue (production method) (13) (8) to (), heated and maintained at 70 ° C. (aqueous phase). On the other hand, (1) to (7), (9) to (12)
Are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring.

(Example 13) Cream (composition component) (mass%) (1) Solid paraffin 5.0 (2) Beeswax 10.0 (3) Vaseline 15.0 (4) Liquid paraffin 41.0 ( 5) Glycerin monostearate 2.0 (6) Polyoxyethylene (20 mol) sorbitan monolaurate 2.0 (7) Soap powder 0.1 (8) Borax 0.2 (9) Luehea ochrophylla extract (Acetone extraction. Solid content) 0.05 (10) Luehea paniculata extract (Ethanol extraction. Solid content) 0.05 (11) Sodium hydrogen sulfite 0.03 (12) Ethylparaben 0.3 (13) Fragrance Suitable amount (14) Ion-exchanged water (7) and (8) were added to the residue (production method) (14) and heated to 7
Keep at 0 ° C (aqueous phase). On the other hand, (1)-(6), (9)-
(14) is mixed, melted by heating, and maintained at 70 ° C (oil phase).
The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After the reaction is completed, the mixture is uniformly emulsified with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

(Example 14) Emulsion (composition component) (mass%) (1) Stearic acid 2.5 (2) Cetyl alcohol 1.5 (3) Vaseline 5.0 (4) Liquid paraffin 10.0 (5) Polyoxyethylene (10 mol) monooleate 2.0 (6) Polyethylene glycol 1500 3.0 (7) Triethanolamine 1.0 (8) Carboxyvinyl polymer 0.05 (“Carbopol 941”) , BFGoodrich) (9) Luehea rufescens extract (acetic acid ethyl ester extraction, solid content) 0.01 (10) sodium bisulfite 0.01 (11) ethylparaben 0.3 (12) perfume proper amount (13) ion Exchanged water Residue (production method) Dissolve (8) in a small amount of (13) (Phase A).
On the other hand, (6) and (7) were added to the remaining (13), which was heated and melted and maintained at 70 ° C. (aqueous phase). (1)-(5), (9)
~ (12) are mixed, melted by heating and kept at 70 ° C (oil phase). The oil phase is added to the aqueous phase, preliminary emulsification is performed, phase A is added, and the mixture is uniformly emulsified with a homomixer. After emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

(Example 15) Emulsion (composition component) (mass%) (1) Microcrystalline wax 1.0 (2) Beeswax 2.0 (3) Lanolin 20.0 (4) Liquid paraffin 10.0 (5) Squalane 5.0 (6) Sorbitan sesquioleate 4.0 (7) Polyoxyethylene (20 mol) sorbitan monooleate 1.0 (8) Propylene glycol 7.0 (9) Arctium lappa extraction Substance (acetone extraction. Solid content) 1.0 (10) Sodium bisulfite 0.01 (11) Ethylparaben 0.3 (12) Perfume proper amount (13) Ion-exchanged water Residue (production method) (13) ( 8) is added, heated and kept at 70 ° C. (aqueous phase). On the other hand, (1) to (7), (9) to (12)
Are mixed, heated and melted and maintained at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added to this, and the mixture is uniformly emulsified with a homomixer. After emulsification, mix well at 30 ℃
Cool down.

(Example 16) Jelly (composition component) (mass%) (1) 95% ethyl alcohol 10.0 (2) dipropylene glycol 15.0 (3) polyoxyethylene (50 mol) oleyl alcohol Ether 2.0 (4) Carboxyvinyl polymer 1.0 (“Carbopol 940”, BFGoodrich) (5) Caustic soda 0.15 (6) L-arginine 0.1 (7) Arctium minus extract (50% ethanol) Extraction solution, concentration 1.5%) 7.0 (8) 2-hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 (9) Ethylenediaminetetraacetate.3Na.2 water 0.05 (10) Methylparaben 0.2 (11) ) Fragrance A suitable amount (12) Ion-exchanged water Dissolve (4) uniformly in the residue (production method) (12) (aqueous phase).
On the other hand, (7) and (3) are dissolved in (1) and this is added to the aqueous phase. Next, after adding (2) and (8) to (11) here, it is neutralized and thickened with (5) and (6).

(Example 17) Beauty liquid (composition component) (mass%) (Phase A) Ethyl alcohol (95%) 10.0 Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl ethyl ether 0.1 Anemopaegma arvense extract (methanol extraction; solid content) 1.5 Methylparaben 0.15 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0. 03 Carboxyvinyl polymer 0.2 (“Carbopol 940”, BFGoodrich) Purified water Residue (production method) Phase A and C were uniformly dissolved, and A was added to phase C
Add phase and solubilize. Then, after adding phase B, it is filled in a container.

Example 18 Pack (composition component) (mass%) (A phase) dipropylene glycol 5.0 polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) Anemopaegma glaucum extract (Methanol extraction. Solid content) 0.01 Olive oil 5.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Perfume 0.2 (Phase C) Sodium hydrogen sulfite 0.03 Polyvinyl alcohol (saponification degree 90, polymerization degree 2,000) 13.0 Ethanol 7.0 Purified water Residual (manufacturing method) A phase, B phase, and C phase are uniformly dissolved, respectively.
Phase B is added to the phase to solubilize it. This is then added to phase C and then filled into a container.

(Example 19) Solid foundation (composition component) (mass%) (1) Talc 43.1 (2) Kaolin 15.0 (3) Sericite 10.0 (4) Zinc white 7.0 (5) Titanium dioxide 3.8 (6) Yellow iron oxide 2.9 (7) Black iron oxide 0.2 (8) Squalane 8.0 (9) Isostearic acid 4.0 (10) POE sorbitan monooleate 3 .0 (11) Isocetyl octoate 2.0 (12) Erythroxylum vaccinifolium extract 1.0 (ethanol extract, concentration 2.0%) (13) Preservative appropriate amount (14) Perfume appropriate amount (production method) (1) to The powder component (7) is thoroughly mixed with a blender, and the oil component (8) to (11), (1
After adding 2), (13) and (14) and thoroughly kneading, the mixture is filled into a container and molded.

(Example 20) Emulsion type foundation (cream type) (composition component) (mass%) (powder part) titanium dioxide 10.3 sericite 5.4 kaolin 3.0 yellow iron oxide 0.8 Red iron oxide 0.3 Black iron oxide 0.2 (Oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (Aqueous phase) Purified water 51.0 1,3- Butylene glycol 4.5 Margaritaria nobilis extract (ethanol extraction. Solid content) 1.5 Sorbitan sesquioleate ester 3.0 Preservative proper amount Fragrance proper amount (manufacturing method) Powder that was thoroughly mixed and pulverized after heating and stirring the aqueous phase Add the body and homogenize. Further, the heated and mixed oil phase is added and treated with a homomixer, and then the fragrance is added with stirring and cooled to room temperature.

The cosmetics of Examples 1 to 20 are all M
Excellent MPs activity inhibitory action.

[0107]

As described above, the MMP of the present invention
The s activity inhibitor has an excellent MMPs activity inhibitory effect,
Skin extracellular matrix components that are deeply associated with skin aging (eg, elastin, laminin, proteoglycans,
Prevents the decomposition of basement membrane components, collagen, etc.) to retain fibers, prevent, prevent, and improve aging of the skin, and maintain the skin's elasticity, wrinkles and sagging, and youthful skin condition. You can

Continuation of the front page (51) Int.Cl. ⁷ Identification code FI Theme Coat (reference) A61K 35/78 A61K 35/78 CE EJLT A61P 43/00 111 A61P 43/00 111 (72) Inventor Sea Salt Kenichi 2-2-1, Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa Shiseido Research Center, Inc. (Shin-Yokohama) (72) Inventor Koji Kobayashi 2-2-1, Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa Prefecture Shiseido Research Center (Shin-Yokohama) (72) Inventor Masahiro Ota 2-2-1, Hayabuchi, Tsuzuki-ku, Yokohama City, Kanagawa Prefecture Shiseido Research Center (Shin-Yokohama) Company F-term (reference) 4C083 AA111 AA112 AA122 AB032 AB212 AB232 AB242 AB272 AB352 AB432 AB442 AC012 AC022 AC072 AC102 AC122 AC182 AC242 AC352 AC392 AC442 AC482 AC542 AC562 AC582 AC642 AC782 AD042 AD092 AD162 AD172 AD512 AD662 CC03 CC07 CC11 CC12 CC25 CC31 DD23 DD27 DD31 DD41 EE12 FF05 4C088 AB12 AB26 AB33 AB43 AB46 AB59 AB66 AC03 AC04 AC05 AC06 AC11 AC13 AC13 AC05 AC06 AC11 AC13 AC13 A09 BA10 NA14 ZA89 ZC20

Claims (7)

[Claims] 1. Wood Fordia Floribunda (Wo
odfordia floribunda Salisb.), avocado (Persea am
ericana Mill. ), Rhubarb (Rheum sp.), Hosovasenna (Cassia angustifolia Vahl), mangosteen (Ga
rcinia mangostana L.), Cassia (Cinnamomum cassia)
Bl.), Tamarindus (Tamarindus indica L.), Bergenia ciliata (Haw.) Stern
b.), Luehea divaricata Ma
rt. et Zucc.), Luhea Grandiflora (Luehea)
grandiflora Mart. et Zucc.), Luhea ochrophylla Mart., Luhea paniculata Mart. et Zucc., Luehea rufescens A. St. Hil.,
Burdock (Arctium lappa L.), Arctium Minus (Arctium minus), Anemopa Egma Abense (Ane)
mopaegma arvense (Vell.)), Anemopaegma glaucum Mrt. ex DC., Erythroxylum vaccini
folium Mart.), Margaritalia Nobilis (Margarit)
aria nobilis L. f.), and one or more plants selected from Pouteria obtusifolia Baehni, or a solvent extract thereof, and either a gelatinase group or a stromlysin group. An MMPs activity inhibitor, which inhibits the activity of matrix metalloproteinases (MMPs) belonging to the group. 2. An elastin decomposition inhibitor, which is an elastin decomposition inhibitor.
The described MMPs activity inhibitor. 3. The MMPs activity inhibitor according to claim 1, which is a laminin decomposition inhibitor. 4. The MMPs activity inhibitor according to claim 1, which is a basement membrane degradation inhibitor. 5. The MMPs activity inhibitor according to claim 1, which is a proteoglycan degradation inhibitor. 6. Wood Fordia Floribunda (Wo
odfordia floribunda Salisb.), avocado (Persea am
ericana Mill. ), Rhubarb (Rheum sp.), Hosovasenna (Cassia angustifolia Vahl), mangosteen (Ga
rcinia mangostana L.), Cassia (Cinnamomum cassia)
Bl.), Tamarindus (Tamarindus indica L.), Luhea divaricata Mart. Et Zuc
c.), Luehea grandiflo
ra Mart. et Zucc.), Luhea Okrophyra (Luehe
a ochrophylla Mart.), Luhea Paniculata (Lue
hea paniculata Mart. et Zucc.), Luehea rufescensA. St. Hil., Burdock (Arc
tium lappa L.), Arctium minus (Arctium m)
inus), Anemopaegma ar
vense (Vell.)), Anemopa Eggma Graukham (Anemo)
paegma glaucum Mrt. ex DC.), Erythroxylum vaccinifolium Mar
t.), Margaritaria nobilis
is L. f.), and Pouteria obtusifolia (Po
Uteria obtusifolia Baehni), one or more plants selected from the group consisting of uteria obtusifolia Baehni) or a solvent extract thereof, and inhibiting the activity of matrix metalloproteases (MMPs) belonging to the collagenase group. 7. The method according to claim 6, which is a collagen degradation inhibitor.
The described MMPs activity inhibitor.