JP2003342180A - Composition for matrix metalloprotease inhibition and skin external preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a composition for matrix metalloprotease inhibition exhibiting a specific and high inhibition activity against the matrix metalloprotease of which production is induced in fibroblast cells of the dermis by the irradiation of ultraviolet light, and a skin external preparation effective for the prevention and improvement of the aging of a skin accelerated by the irradiation of the ultraviolet light. <P>SOLUTION: This composition for matrix metalloprotease inhibition is obtained by incorporating an extract obtained form the flower or root of Alpinia speciosa in a carrier or base agent, and further the skin external agent is obtained by incorporating 1 kind or ≥2 kinds of the compositions for the matrix metalloprotease inhibition in a base agent for the external agent. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a type I matrix metalloprotease produced by dermal fibroblasts,
The present invention relates to a matrix metalloprotease inhibitory composition exhibiting a specific inhibitory activity, and a skin external preparation containing the same. More specifically, it is selected from extracts obtained from ghetto flowers and roots of ghetto 1.
The present invention relates to a matrix metalloprotease inhibitor composition containing one or more species, and a skin external preparation containing the same, which is particularly effective in preventing skin aging promoted by ultraviolet rays.

[0002]

2. Description of the Related Art In recent years, much knowledge has been obtained regarding the relationship between matrix metalloproteases, which promote the degradation of matrix fibers, and pathological conditions. In the dermis, UV irradiation induces the production of matrix metalloproteinases by fibroblasts, which promotes the degradation of collagen, which is the main component of the dermal extracellular matrix, and causes skin aging such as wrinkle formation and loss of elasticity. Is known to progress.

[0003] In order to improve or prevent such skin aging promoted by ultraviolet rays, an ultraviolet absorber or a scattering agent is added to an external preparation for the skin, and a screening for a substance having an action of eliminating active oxygen generated by ultraviolet irradiation. Has been actively carried out. At the same time, screening for substances that inhibit the activity of matrix metalloproteases involved in the degradation of collagen as described above is also being conducted.

For example, plant extracts such as an acylphenylglycine derivative (JP-A-7-101925), pomegranate seed, lemon balm seed and leaves, guava, hammallis (JP-A-7-196526, 7-291873, 8).
-283133), polyporenic acid and spinach extract containing the same (JP-A-9-40552), dicarboxylic acid (JP-A-9-124472), substances produced by Aspergillus microorganisms (JP-A-9-241287) and the like. There is.

However, among the compositions for inhibiting matrix metalloproteinases obtained thus far, those showing strong activity against bacterial collagenase and the like and having low specificity for interstitial matrix metalloproteases Some had insufficient activity and some lacked stability.

In addition, ursolic acids, loquats and peaches of the Rosaceae family, buckthorn family jujube, asteraceae cornflower, perilla family thyme, rosemary, sage, perilla, and duckweed plant have the action of improving the disorder of dermal collagen fiber bundles. It is known that the extract of Pleurotus cornucopiae and Pleurotus cornucopiae require a long period of time to reconstruct collagen fibers by using them, and that it is desirable to use the substance in combination with a substance having an anti-inflammatory action (Japanese Patent Laid-Open No. H11 (1999) -111945). -1212
2).

On the other hand, ghetto (Momochi, Alpinia speciosa
(Wendl.) K. Schum.), Also known as Sannin, is the genus Gingidae ( Zingiberaceae ) of the genus Alpini.
It is a plant of a ) that has been used for a long time in Okinawa where the essential oil components obtained from the leaves are known to have antioxidant, antiseptic, deodorant and insecticidal effects. Many reports have been made on the analysis of essential oil components and the usage of essential oils.

Regarding the utilization of ghetto extract in the field of cosmetics, a bathing agent containing syrup obtained by squeezing raw leaves of tyring ghetto, a kind of ghetto, and crushed and dried, as an active ingredient (JP-A-11-349471), ghetto A cosmeceutical composition containing an extract or squeezed liquid from leaves or stems, which is effective in improving acne and rough skin (JP 2000-1
91493), a hair-growth agent or hair-growth agent containing a ghetto extract (mainly essential oil) as an active ingredient (JP-A-2000-35).
5525), an antioxidant containing a ghetto extract, (Japanese Patent Laid-Open No. 9-615), a fibroblast proliferation promoting action, a cell activating action, a collagen production promoting action, and a collagenase inhibiting action of a ghetto leaf or stem extract (special feature). Open 2001-316
275, 2002-3390, Fragrance Journal, 5 , 86-91 (2001)), and various effects of ghetto extract have been noted.

However, attention is paid to the effectiveness of the extract from the flower or root of ghetto, and nothing is known about its application as a composition for inhibiting matrix metalloproteinases.

[0010]

DISCLOSURE OF THE INVENTION In the present invention, a matrix metalloprotease inhibitory composition having a specific and high inhibitory activity against a matrix metalloprotease whose production is induced in dermal fibroblasts by UV irradiation is obtained. Furthermore, it was intended to provide a skin external preparation effective for preventing and improving skin aging promoted by ultraviolet irradiation using the same.

[0011]

[Means for Solving the Problems] In order to solve the above problems, screening was performed using the inhibitory activity against matrix metalloproteinases produced by dermal fibroblasts as an index. As a result, the extract obtained from the flower of ghetto and the extract obtained from the root of ghetto show good inhibitory activity, and can further stably retain the inhibitory activity even in the preparation for external preparation for skin, and to the skin. I also found that it is highly safe. These can effectively inhibit the subsequent production of matrix metalloprotease when coexisted during UV irradiation,
The present inventors obtained a matrix metalloprotease inhibitory composition according to the present invention by incorporating one or more selected from the above extracts into a carrier or a base. Then, using this composition for inhibiting matrix metalloprotease, a skin external preparation effective for preventing and improving skin aging promoted by ultraviolet rays was obtained.

That is, in the present invention, one or two or more kinds selected from an extract obtained from a ghetto flower and an extract obtained from a ghetto root are used as they are or in a carrier or a base, and a matrix metallo A composition for protease inhibition is prepared, and further, one or more kinds of the composition for matrix metalloprotease inhibition is incorporated into an external preparation base to obtain a skin external preparation.

[0013]

DETAILED DESCRIPTION OF THE INVENTION Getto ( Alpinia speciosa (We
ndl.) K. Schum.) is a plant belonging to the genus Ginger ( Zingiberaceae ) and belonging to the genus Hanamyoga ( Alpinia ). In the present invention, an extract obtained from a flower or a root is
Each is appropriately selected and used.

The ghetto may be subjected to extraction as it is, but in view of extraction efficiency, it is preferable to carry out extraction after processing 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.

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, and 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. Above all, it is preferable to use a 50% by volume aqueous ethanol solution as the extraction solvent.

The extract of ghetto flowers or roots with the above solvent can be added as it is to the composition for inhibiting matrix metalloprotease, but the concentrated and dried product can be redissolved in water or a polar organic solvent, or It may be added after purification treatment such as decolorization and deodorization is carried out within a range not impairing the matrix metalloprotease inhibitory action.
For storage, it is preferable to freeze-dry after purification and dissolve in a solvent before use.

As the composition for inhibiting matrix metalloproteinase according to the present invention, one or two or more selected from the extract of ghetto flowers or roots with the above solvent is used as it is or added to a carrier. Get it. As the carrier, water, a polar organic solvent such as ethanol, propanol, butanol and lower alcohols, a liquid carrier such as a mixture thereof, various emulsions, various cream bases, ointment bases, gels, powders and the like can be used. . Therefore, the composition for inhibiting matrix metalloproteinase according to the present invention can be provided in the form of lotion, suspension, emulsion, cream, ointment, gel, powder and the like. Further, it may be contained in liposomes or microcapsules. The matrix metalloprotease inhibitory composition according to the present invention contains an antioxidant, a fungicide / antifungal agent, a stabilizer such as an ultraviolet absorber, an absorption promoter, etc. within a range that does not impair the characteristics of the present invention. It can also be added.

Further, in the present invention, one or more of the above-described matrix metalloprotease inhibiting compositions are contained in an external preparation base to provide a skin external preparation effective for preventing and improving skin aging. provide. The external preparation for skin can be provided in the form of lotion, suspension, emulsion, cream, ointment, gel and the like. In addition, cosmetics for skin such as lotion, milky lotion, cream and pack, lotion or cream for makeup base, makeup cosmetics such as various emulsions, creams, ointments, solid foundations, sunscreen lotions or It can also be provided as a sunscreen cosmetic such as cream, a hand lotion or cream, a leg lotion or cream, a body cosmetic such as a body lotion or cream.

Also in the external preparation for skin according to the present invention, in addition to the composition for inhibiting matrix metalloprotease,
Various oils, surfactants, lower alcohols, humectants, polyhydric alcohols, cell activating agents, antioxidants, whitening agents, UV absorbers, antibacterial and antifungal agents, within the range not impairing the features of the present invention.
It is possible to add general skin external preparation additive components such as pigments, pigments, and fragrances.

As a blending amount per the total amount of the external preparation for skin,
Although it depends on the preparation method, it is suitable to be about 0.0001 to 5.0% by weight.

[0021]

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

First, examples of the composition for inhibiting matrix metalloproteinase according to the present invention will be shown.

[Example 1] 250 g of ghetto flowers were dried and pulverized, immersed in 2 liters of 50% by volume ethanol solution at 20 ° C for 7 days, filtered to collect the filtrate, and then rotary evaporator was used. It was concentrated under reduced pressure and further freeze-dried to obtain ghetto extract 1.

[Example 2] 250 g of the root part of ghetto were dried and pulverized, immersed in 2 liters of 50% by volume ethanol solution at 20 ° C for 7 days, and then filtered to collect the filtrate, which was then rotary evaporated. It was concentrated under reduced pressure and further freeze-dried to obtain ghetto extract 2.

In Examples 1 and 2 described above, the inhibitory effect on type I matrix metalloprotease production induced by ultraviolet irradiation was evaluated as follows. First, human fibroblasts were seeded on a 96-well plate at 2 × 10 ⁴ cells / well, and fetal calf serum 5 (w / v) was added.
% In Dulbecco's basal medium (DMEM)
It was cultured at 7 ° C for 24 hours. After washing with the Hanks (+) solution, the medium was replaced with 0.1 mL of the Hanks (+) solution containing the sample, and the long wavelength ultraviolet light (UVA) of 8 J / cm ² was irradiated. Then, the medium was exchanged with DMEM containing 0.1 (w / v)% bovine serum albumin and cultured at 37 ° C. for 24 hours, then the number of viable cells was counted, and the type I matrix metalloproteinase activity in the medium supernatant was measured. Was measured. The type I matrix metalloprotease activity in the medium supernatant was 0.
After addition of 05 mg / mL trypsin and incubation at 37 ° C. for 15 minutes, final concentration of 0.25 mg / mL
Was added to the soybean trypsin inhibitor composition, which was measured using type I collagen labeled with fluorescein isothiocyanate (FITC) as a substrate.
That is, 100 mM Tris-HCl buffer solution (pH containing 0.25 mg / mL FITC-labeled type I collagen)
7.5, containing 0.4M sodium chloride, 0.01M calcium chloride and 0.04 (w / v)% sodium azide)
50 μL was added to the trypsinized medium supernatant 50 μL
In addition to the above, the mixture was allowed to react at 37 ° C. for 2 hours in the dark. Then 40 mM o-phenanthroline 5
After the reaction was stopped by adding μL, the collagen was denatured at 37 ° C. for 30 minutes, and the volume ratio of ethanol and 0.17 M Tris-HCl buffer (pH 9.5, containing 0.67 M sodium chloride) was 7: 50 μL of the mixed solution of 3 was added,
Only denatured collagen was extracted. 2,000 rp
Centrifuge for 15 minutes at 50 μm and adjust the fluorescence intensity of the supernatant to
The measurement was performed at 95 nm and a fluorescence wavelength of 520 nm.

Regarding Example 1 and Example 2, the relationship between the final concentration of the sample and the type I matrix metalloprotease activity was 100% of the enzyme activity when the sample was not added.
The evaluation was performed by the index shown as.

As a result, Example 1 of the present invention showed a very strong type I matrix metalloprotease inhibitory action,
UVA-induced type I matrix metalloprotease activity at 0.01 mg / mL was 43%, 0.1%.
There was 52% inhibition at mg / mL.

In addition, Example 2 of the present invention also shows a very strong type I matrix metalloprotease inhibitory action, and the UVA-induced type I matrix metalloprotease activity was 70% at 0.39 μg / mL. ,
63% at 1.56 μg / mL, 7 at 6.25 μg / mL
The inhibition was 7% and 61% at 25 μg / mL.

Next, examples of other matrix metalloprotease inhibiting compositions according to the present invention and examples of external preparations for skin will be shown. Unless otherwise specified, the unit weights in the examples are shown by weight%.

Example 3 500 g of ghetto flowers were dried and pulverized, immersed in 2 liters of an 80% by volume aqueous ethanol solution at 20 ° C. for 7 days, filtered, and the filtrate was collected, concentrated and dried. Then, it was dissolved in a 50% by volume aqueous solution of 1,3-butylene glycol to obtain ghetto extract 3.

[Example 4] 500 g of root part of ghetto was dried and pulverized, immersed in 2 liters of 80% by volume aqueous ethanol at 20 ° C for 7 days, filtered to collect the filtrate, concentrated and dried. Then, it was dissolved in a 50% by volume aqueous solution of 1,3-butylene glycol to obtain ghetto extract 4.

[Example 5] Skin lotion (1) Ethanol 10.00 (2) Hydroxyethyl cellulose 1.00 (3) Matrix metalloprotease inhibitory composition (Example 1) 0.10 (4) Paraoxybenzoic acid Methyl 0.10 (5) Purified water volume based on 100 Manufacturing method: (1) to (4) are sequentially added to (5) and dissolved uniformly.

Example 6 Skin Emulsion (1) Stearic Acid 0.20 (2) Cetanol 1.
50 (3) Vaseline 3.00 (4) Liquid paraffin
7.00 (5) Polyoxyethylene (10 E.O.) monooleate 1.50 (6) Tocopherol acetate
0.25 (7) Glycerin 5.00 (8) Methyl paraoxybenzoate 0.10 (9) Triethanolamine 1.00 (10) Purified water Amount based on 100 as a whole (11)
Composition for inhibiting matrix metalloprotease (Example 2) 0.05 Production method: The oil phase components (1) to (6) are mixed and heated to uniformly dissolve them, and the mixture is kept at 70 ° C. On the other hand, the aqueous phase components (7) to (10) are mixed and heated to homogenize the mixture to 70 ° C. The oil phase component is gradually added to this water phase component while stirring to emulsify, and after cooling, (11) is added and mixed at 40 ° C.

Example 7 Skin Gel Agent (1) Dipropylene Glycol 10.00 (2) Carboxyvinyl Polymer 0.50 (3) Potassium Hydroxide
0.10 (4) Methyl paraoxybenzoate 0.10
(5) Purified water in an amount of 100 as a whole (6) Composition for inhibiting matrix metalloprotease (Example 1)
03 (7) Composition for inhibiting matrix metalloprotease (Example 2) 0.03 Production method: (2) was uniformly dissolved in (5), then (4) was dissolved in (1), and then added. After adding (3), the viscosity is increased, and (6) and (7) are added and mixed.

Example 8 Skin cream (oil-in-water type) (1) Beeswax 6.0 (2) Cetanol 5.0
(3) Reduced lanolin 8.0 (4) Squalane 27.
5 (5) Glyceryl fatty acid ester 4.0 (6) Lipophilic glyceryl monostearate ester 2.0 (7)
Polyoxyethylene (20 E.O.) sorbitan monolaurate 5.0 (8) Propylene glycol 5.0
(9) Methyl paraoxybenzoate 0.1 (10) Purified water Amount based on 100 as a whole (11) Composition for inhibiting matrix metalloprotease (Example 1) 0.5 Production method: oils of (1) to (7) The phase components are mixed and heated to dissolve uniformly and kept at 75 ° C. On the other hand, the water phase components (8) to (10) are mixed and heated to homogenize the mixture to 75 ° C. The oil phase component is added to the aqueous phase component to pre-emulsify it, then homogenize with a homomixer, and after cooling, (11) is added and mixed at 40 ° C.

[Example 9] Oil-in-water emulsion type ointment for skin (1) White petrolatum 25.0 (2) Stearyl alcohol 25.0 (3) Glycerin 12.0 (4) Sodium lauryl sulfate 1.0 (5) Methyl paraoxybenzoate 0.1 (6) Purified water based on 100 as a whole (7) Composition for inhibiting matrix metalloprotease (Example 2) 0.5 Production method: (1) to (4) Mix and dissolve to make uniform
Heat to 75 ° C. On the other hand, (5) is dissolved in (6) and heated to 75 ° C., the oil phase component is added thereto to emulsify, and after cooling, (7) is added and mixed at 40 ° C.

Example 10 Sunscreen water-in-oil cream (1) Squalane 38.0 (2) Glyceryl diisostearate 3.0 (3) Paramethoxycinnamic acid
2-Ethylhexyl 3.0 (4) Oxybenzone 1.5
(5) Organically modified bentonite 1.5 (6) Silicone treated titanium oxide 3.0 (7) 1,3-butylene glycol
5.0 (8) Methyl paraoxybenzoate 0.1 (9)
Amount of purified water based on 100 as a whole (10) Composition for inhibiting matrix metalloprotease (Example 1) 1.0 (1
1) Perfume 0.1 Manufacturing method: (1) to (5) are mixed, heated and dissolved, and (6) is dispersed to 70 ° C. to obtain an oil phase. On the other hand, dissolve (8) in (7)
Add to (9), mix, and heat to 70 ° C. The aqueous phase was added to the oil phase, the mixture was homogenized, emulsified, and cooled.
Add (11) at ℃ and mix.

[Example 11] Makeup base cream (1) Stearic acid 12.00 (2) Cetanol
2.00 (3) Glyceryl tri-2-ethylhexanoate 2.50 (4) Self-emulsifying glyceryl monostearate 2.00 (5) Propylene glycol 10.00 (6) Methyl paraoxybenzoate 0.1
0 (7) Potassium hydroxide 0.30 (8) Purified water 100 as the total amount (9) Titanium oxide 1.00 (10) Red iron oxide 0.10 (11) Yellow iron oxide 0.40 (12) Matrix metallo Composition for Protease Inhibition (Example 3)
0.02 (13) Perfume 0.10 Manufacturing method: The oil phase components (1) to (4) are mixed and heated to uniformly dissolve them, and kept at 75 ° C. On the other hand, mix the water phase components (5) to (8),
The mixture is heated to homogeneity, (9) to (11) are added thereto, and the mixture is uniformly dispersed with a homomixer, and then the temperature is raised to 75 ° C. After preliminarily emulsifying by adding the oil phase component to the water phase component, homogenize with a homomixer, and after cooling at 40 ° C. (12), (13)
Add and mix.

Example 12 Milky liquid foundation (1) Stearic acid 2.0 (2) Squalane 5.0
(3) Octyldodecyl myristate 5.0 (4) Cetanol 1.0 (5) Decaglyceryl monoisopalmitate 9.0 (6) 1,3-butylene glycol 6.0 (7) Potassium hydroxide 0.0. 1 (8) Methyl paraoxybenzoate 0.1 (9) Amount of purified water to be 100 as a whole (10) Titanium oxide 9.0 (11) Talc 7.4
(12) Red iron oxide 0.5 (13) Yellow iron oxide 1.1 (14)
Black iron oxide 0.1 (15) Matrix metalloprotease inhibitor composition (Example 4) 5.0 (16) Perfume 0.1.
1. Manufacturing method: The oil phase components of (1) to (5) are mixed, heated and uniformly dissolved, and kept at 75 ° C. On the other hand, the water phase components (6) to (9) are mixed and heated to homogenize, (10) to (14) are added thereto, and the mixture is homogenized with a homomixer and then heated to 75 ° C. After preliminarily emulsifying by adding the oil phase component to the water phase component, the mixture is uniformly emulsified with a homomixer, and after cooling at 40 ° C. (15),
Add (16) and mix.

[Example 13] Oily ointment type foundation (1) Solid paraffin 3.0 (2) Microcrystalline wax 6.0 (3) Beeswax 2.0 (4) Vaseline 12.0 (5) Lanolin acetate 1. 0 (6) Squalane 6.0 (7) Isopropyl palmitate 1
6.0 (8) Vitamin E 0.2 (9) Matrix metalloprotease inhibitor composition (Example 2) 2.0
(10) Talc 17.5 (11) Kaolin 15.0 (1
2) Titanium oxide 15.0 (13) Red iron oxide 1.0 (14)
Yellow iron oxide 3.0 (15) Black iron oxide 0.2 (16) Fragrance
0.1 Manufacturing method: (1) to (8) are melted at 85 ° C., and (9) is added thereto,
After mixing, (10) to (15) are thoroughly mixed, ground, and added with stirring. Then disperse with a colloid mill,
After 6) is added, mixed and deaerated, it is poured into a container at 70 ° C. and cooled.

Example 14 Hand Cream (1) Cetanol 4.00 (2) Vaseline 2.00
(3) Liquid paraffin 10.00 (4) Glyceryl monostearate 1.50 (5) Polyoxyethylene (60 E.O.) glyceryl isostearate
2.50 (6) Tocopherol acetate 0.50 (7) Glycerin 20.00 (8) Methyl paraoxybenzoate 0.10 (9) Purified water 59.38 (10) Matrix metalloprotease inhibitory composition (Example 3) ) 0.
01 (11) Composition for inhibiting matrix metalloprotease (Example 4) 0.01 Production method: The oil phase components of (1) to (6) are mixed and heated to uniformly dissolve them, and kept at 75 ° C. On the other hand, mix the water phase components (7) to (9),
Heat to homogeneity to 75 ° C. The oil phase component is added to the aqueous phase component to pre-emulsify it, then homogenize with a homomixer, and after cooling, (10) and (11) are added and mixed at 40 ° C.

Among the examples of the external preparation for skin according to the present invention, Examples 5 to 9 were evaluated for the effect of preventing the generation of wrinkles due to ultraviolet rays. In addition, in each Example, the composition prepared by substituting the composition used for inhibiting the matrix metalloprotease of Examples 1 to 4 with the solvent used for each preparation was set as Comparative Example 1 to Comparative Example 4, and at the same time, An evaluation was made. The effect of preventing the generation of wrinkles was set to 5 hairless mice as a group, and 0.2 g of each of the Examples and Comparative Examples was applied to the back once a day for each group, and 1 J / cm ² / week of UVA was applied for 50 weeks. The hairless mice were irradiated and observed for wrinkle generation, and scored according to the criteria shown in Table 1. At this time, a group to which only purified water was applied served as a control. The results were calculated by calculating the average value of each group, and the relationship with the number of UVA irradiation days was shown in Table 2.
It was shown to.

[0043]

[Table 1]

[0044]

[Table 2]

As shown in Table 2, in the control group, the depth of the wrinkles formed reached a medium level when the number of UVA irradiation days exceeded 40 weeks, and deep wrinkles occurred after 50 weeks. Was admitted. On the other hand, in the groups applied with the examples of the present invention, the suppression of the occurrence of significant wrinkles was observed in all cases, and the minute or slight wrinkles were observed after 50 weeks. Particularly, in the coating groups of Examples 5, 8 and 9, remarkable wrinkle suppression was observed. On the other hand, in the Comparative Example-applied group, a slight reduction in the degree of wrinkles occurring in the Comparative Example 2-applied group containing tocopherol acetate was observed, but no significant wrinkle suppression or reduction was observed.

Next, a usage test by a female panelist was conducted. Also in this case, Example 1 compounded in each Example
-Comparative examples 1 to 10 were prepared by substituting the solvent used for the preparation of the matrix metalloprotease inhibiting composition of Example 4. Use test is 2
One 20-year-old to 50-year-old woman working outdoors normally
Each group was made to use each of the examples and comparative examples twice a day for one month from the middle of May to the middle of June, and the wrinkles of the skin and changes in skin elasticity before and after use were observed. It was done. Wrinkles on the skin were evaluated by visual evaluation after photography and by a replica method, and skin elasticity was evaluated by measurement with a cut meter. Result is,
The skin wrinkles and skin elasticity after use were evaluated for each panel in 5 grades of "improved", "slightly improved", "no change", "slightly deteriorated", and "deteriorated" in comparison with those before use. The number of evaluated panelists is shown in Table 3.

[0047]

[Table 3]

As is clear from Table 3, in any of the groups used in the examples of the present invention, no panelists recognized wrinkles on the skin and a tendency for deterioration of skin elasticity, and wrinkles on the skin were 80% or more, skin elasticity was Was evaluated as improved or slightly improved by 90% or more of the panelists. In particular, a high improvement rate was observed in the group using Example 10 in which the ultraviolet absorber was used in combination. On the other hand, in the comparative example use group, no panelists were found to have been clearly improved in skin wrinkles and skin elasticity, and the symptoms were observed in skin wrinkles of 75% or more and skin elasticity of 65% or more. No improvement was seen. In addition, except for the group used in Comparative Example 6, 10 to 35% of the panelists observed a tendency of worsening of each symptom. Also in the group using Comparative Example 6 containing the ultraviolet absorber, the skin wrinkles and the skin elasticity were slightly worse in 1 person and 2 people, respectively, and both skin wrinkles and skin elasticity tended to improve. The number of panelists was significantly smaller than that of the corresponding group using Example 10.

In Examples 5 to 14 of the present invention, no change in state such as precipitation, separation, aggregation, discoloration or odor of the contained components was observed during the above-mentioned use period. Further, in the use groups of each Example, no panelists showed skin irritation reaction or skin sensitization reaction.

[0050]

INDUSTRIAL APPLICABILITY As described in detail above, according to the present invention, a matrix metalloprotease inhibitory composition showing specific and high inhibitory activity against matrix metalloprotease whose production is induced in dermal fibroblasts by ultraviolet irradiation. Further, by using this, it was possible to provide a skin external preparation effective for preventing and improving skin aging promoted by ultraviolet irradiation.

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Claims (4)

[Claims] 1. A composition for inhibiting matrix metalloprotease, which comprises an extract obtained from ghetto flowers. 2. A composition for inhibiting a matrix metalloprotease, which comprises an extract obtained from ghetto root. 3. The matrix metalloprotease is I
Composition according to claim 1 or 2, characterized in that it is a type matrix metalloprotease. 4. An external preparation for skin comprising the composition according to claim 1.