JP2001181129A - Collagenase activity inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a collagenase activity inhibitor which has an inhibiting effect on the activity of collagenase having remarkable influence on aging of the skin, prevents the degeneration and involution of collagen and can protect strands. SOLUTION: This collagenase activity inhibitor comprises one or more plants selected from the group consisting of Annona muricata L., Calophyllum brasiliense Cambess., Cleome hassleriana Chodat. and Myrcia sphaerocarpa DC. or solvent extract thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a collagenase activity inhibitor containing a specific plant or a solvent extract thereof. The collagenase inhibitor of the present invention has excellent antagonism to collagenase activity and is excellent in safety.
The present invention includes basic cosmetics, makeup cosmetics,
It can be suitably used for hair cosmetics, bath preparations and the like.

[0002]

2. Description of the Related Art Hitherto, it has been known that changes associated with aging of the skin, that is, wrinkles, dullness, disappearance of texture, decrease in elasticity, etc., cause a decrease in fibrous and denaturation of dermal matrix such as collagen and elastin. ing.

In recent years, research has been advanced, and matrix metalloproteases (MM
Ps; Matrix Metalloproteinases) has been pointed out. Matrix proteases are classified into several groups in terms of their structure and function. Among them, those belonging to the collagenase group include MMP-1 (interstitial collagenase), MMP-8, MMP-13 and the like.
Among the enzymes belonging to the collagenase group, particularly MM
P-1 is known as an enzyme that degrades the type I and III collagens, which are the main components of the dermis matrix of the skin. Become one,
This is considered to be one of the major factors such as the formation of skin wrinkles. MMP-8 and MMP-13 also have the action of decomposing type I collagen and the like.

[0004] Therefore, inhibiting collagenase activity protects collagen and protects the matrix forming fibers, and is important in preventing skin aging.

[0005] However, many conventional anti-aging preparations have a mechanism of activating fibroblasts and increasing the amount of collagen production, and some of them focus on inhibition of collagenase activity. Absent.

[0006]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies in view of the above circumstances, and as a result, have found that an extract of a specific plant has an excellent collagenase activity inhibitory action, and completed the present invention. I came to. INDUSTRIAL APPLICABILITY The present invention has a collagenase activity inhibitory effect that greatly affects skin aging, prevents collagen denaturation and regression, protects fibers, and can effectively prevent, prevent, and improve skin aging.

[0007]

Means for Solving the Problems That is, the present invention relates to a method comprising the steps of producing a thorny reed (Annona muricata L.), a calophyllum brasiliense Cambess.
Cleome hassleriana Choda
t.), and Milkia sphaerocarpa (Myrcia sph)
aerocarpa DC.) or a collagenase activity inhibitor containing a solvent extract thereof.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

[0009] The thorny reed used in the present invention (Anno
na muricata L.) is a plant belonging to the family Annonaceae (Annonaceae). Bark reed (A. muricata) is native to tropical America and is currently planted in tropical regions of the world, with roots used as antidote for poisoning,
The leaves are used for rheumatism and vegetation, the flowers are used for abdominal pain, insertion, rheumatism, neuralgia and coughing, and the fruits are used for carminative wind, diuresis, astringent and emetic.

[0010] Calophyl brasiliense (Calophyl
lum brasiliense Cambess.) is a family of Hypericum (Futaceae) (Guttiferae, Hypericaceae)
lophyllum). Carophyllum brasiliense (C. brasiliense) is distributed in tropical America and is also known as Santa Maria and is known as a good material. The resin is called Jacareuba Balsam or Landin Balsam and is aromatic and used for rheumatism and ulcers.

Cleome hassler
iana Chodat.) is the family of Capriidaceae (Capparidaceae)
It is a plant belonging to the genus Cleome. Cleome hassleriana (C. hassleriana) is an annual plant distributed in Brazil, Paraguay and Argentina.
The leaves are used as a decoction for healthy stomach, digestion, gonococcal inflammation, and lower back. For external use, wounds and orchitis are used. Herbal juice is used for otitis media.

[0012] Milkia sphaerocarpa (Myrcia sph)
aerocarpa DC.) is a plant belonging to the family Myrtaceae (Myrcia). Milkia sphaerocarpa (M. sphaerocarpa) is a sub-tree that is distributed in Brazil, Guiana, Peru and Paraguay. Its bark and leaves are widely used as tea and decoction in diabetes, and are commonly known as vegetable insulin.

As described above, each of the above-mentioned plants used in the present invention is known to have various pharmacological activities, but none of the plants has been known to have a collagenase activity inhibitory effect. This time, the present inventors have found it for the first time.

Each of the above-mentioned plants used in the present invention can be used either raw or dried.
It is preferably used as a dry powder or a solvent extract from the viewpoint of formulation and the like.

[0015] The sites of use of the above plants include leaves, branches,
Any part of each plant, such as flowers, roots, fruits, seeds, bark, etc. can be used, but the following parts are particularly preferably used.

In the case of A. muricata, it is particularly preferable to use leaves, but other sites may be used.

Carophilum brasiliense (C. brasi)
liense; Santa Maria), it is preferable to use bark, but other parts can also be used.

C. hasslerian
In a), it is preferable to use a stem, but other parts can be used.

Milkia sphaerocarpa (M. sphaero)
In carpa), the use of leaves is preferred, but other sites may be used.

The extract of each of the above-mentioned plants can be obtained by a conventional method. For example, each of the above-mentioned plants can be obtained by immersing or heating under reflux with an extraction solvent, followed by filtration and concentration. As the extraction solvent, any solvent can be used as long as it is a solvent usually used for extraction. For example, water, alcohols such as methanol, ethanol, propylene glycol, 1,3-butylene glycol and glycerin, hydrous alcohols, chloroform And organic solvents such as dichloroethane, carbon tetrachloride, acetone, ethyl acetate, hexane and the like 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 adsorbed by a column of a porous polymer (eg, Amberlite XAD-2). After the reaction, elution with methanol or ethanol and concentration can also be used. Also the distribution method, for example water /
An extract extracted with ethyl acetate is also used.

In addition, A. muricata,
C. brasiliense; Santa
Maria), it is particularly preferable to perform the extraction twice.
Specifically, for example, it is preferable to use one obtained by extracting a plant residue with methanol or the like after extracting with dichloromethane.

Each of the above plant extracts thus obtained is
It is highly safe and has an excellent collagenase activity inhibitory action.

In the present invention, "collagenase activity inhibitor" refers to a matrix metalloprotease (MMP).
In s), preparations that directly or indirectly inhibit the activity expression of enzymes classified into the collagenase group are broadly meant. Here, the enzymes belonging to the collagenase group include MMP-1, MMP-8, MMP-13 and the like.

The collagenase activity inhibitor of the present invention can be suitably used, for example, as an external preparation for skin. In this case, the amount of each of the above plant extracts is 0.0001 to 20 as a dry weight in the total amount of the external preparation. Weight percent is preferred,
In particular, it is 0.001 to 10% by weight. If the amount is less than 0.0001% by weight, the effects of the present invention cannot be sufficiently exerted. On the other hand, if the amount is more than 20% by weight, a remarkably large improvement in the effect cannot be recognized, and it is not preferable because formulation becomes difficult.

The collagenase activity inhibitor of the present invention can be suitably used in the fields of cosmetics, pharmaceuticals, and quasi-drugs. In this case, in addition to the above plant extracts, the effect of the present invention is not impaired. Within, other components usually used for external preparations such as cosmetics and pharmaceuticals, for example, whitening agents, humectants,
Antioxidants, oily components, UV absorbers, surfactants, thickeners, alcohols, powder components, coloring agents, aqueous components, water,
Various skin nutrients and the like can be appropriately compounded as needed.

Further, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and derivatives thereof, and licorice extract Products, glabridine, hot water extract of karin fruit, various crude drugs, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid, etc. Whitening agent, glucose, fructose, mannose,
Sugars such as sucrose and trehalose, and vitamin A derivatives such as retinoic acid, retinol, retinol acetate, retinol palmitate, and the like can also be appropriately blended.

In the present invention, the dosage form is not particularly limited, but may be a solution type, a solubilizing type, an emulsifying type, a powder dispersing type, a water type,
An arbitrary dosage form such as an oil two-layer system, a water-oil-powder three-layer system, an ointment, a gel, and an aerosol is applied.

[0028] The form of use is also optional. For example, it is used for facial cosmetics and foundations such as lotions, emulsions, creams and packs, as well as makeup cosmetics, hair cosmetics, aromatic cosmetics, bath preparations and the like. However, it is needless to say that the present invention is not limited to these examples.

[0029]

Next, the present invention will be described in more detail with reference to Examples, but the technical scope of the present invention is not limited by these Examples.

Prior to the examples, test methods and evaluation methods for the collagenase activity inhibitory effect of the plant extract used in the present invention will be described.

[Test Method and Evaluation Method]

1. Preparation of Sample As shown in Table 1, each plant was immersed in a solvent to obtain an extract. This extract was concentrated and carbonized to obtain each plant extract. The immersion in the solvent was performed at room temperature for about one week.

Each of the plant extracts was dissolved in dimethyl sulfoxide (DMSO) to a concentration of 2%.
A solution containing a plant extract was used.

Each of the plant extract-containing solutions was added to a measuring solution (0.4 M NaCl, 10 mM CaCl _2).
The solution was diluted with 0.1 M Tris (pH 7.4 containing pH 7.4) to adjust the concentration, and this was used as a sample solution (samples 1 to 5), and the following experiment was performed.

2. Collagenase Activity Inhibitory Effect A collagenase (enzyme) extracted from a human-derived cell (manufactured by mussel) was used, and a substrate used was fluorescein isothionate-labeled type I collagen (manufactured by mussel).

A mixture of 50 μl of the above sample solution, 100 μl of an enzyme solution containing a certain amount of enzyme (0.4 unit / ml) and 50 μl of a substrate solution (1 mg / ml) was added at 37 ° C. for a certain time (2 to 4 hours). After incubating with
After stopping the enzymatic reaction by adding an ethanol solution, unreacted fluorescent-labeled collagen was precipitated by centrifugation, the fluorescence intensity of the degraded substrate remaining in the supernatant was measured, and the degradation rate of type I collagen was determined.

The ratio of the degradation rate of the system containing the plant extract (the sample solution) to the degradation rate of the collagen in the reaction system containing no plant extract (control: DMSO) is determined by The collagenase activity inhibition rate of the product was determined. Table 2 shows the results.

As a reference example, the same test as described above was conducted for ethylenediaminetetraacetic acid (EDTA), which is a substance whose collagenase inhibitory action is well known.
The results are shown in Table 2.

[0039]

[Table 1]

[0040]

[Table 2]

As is clear from Table 2, the inhibitory effect of each plant extract used in the present invention on collagenase activity was ED
It was extremely superior to the collagenase activity inhibitory effect of TA.

The following are prescription examples of the present invention.

(Example 1) Cream (combination component) (% by weight) (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) Annona muricata extract (methanol extract) 0.01 (7) Caustic potassium 0.2 (8) Sodium bisulfite 0.01 (9) Preservative suitable Amount (10) Perfume appropriate amount (11) Ion-exchanged water residue (Preparation method) (5) to (7) were added to (11), dissolved, heated and maintained at 70 ° C (aqueous phase). On the other hand, (1) to (4),
(8) to (10) were mixed, melted by heating, and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase, and after the addition was completed, the temperature was maintained for a while to cause a reaction. Thereafter, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well to obtain a cream.

(Example 2) Cream (combination component) (% by weight) (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) Calophyllum brasiliense extract 0.05 (dichloromethane extract) (10) Sodium bisulfite 0.03 (11) Ethylparaben 0.3 (12) Appropriate amount of perfume (13) Ion-exchanged water residue (Preparation method) (13) (8) was added and heated to 70 ° C. (aqueous phase). On the other hand, (1) to (7), (9) to (1)
2) was mixed, heated and melted, and kept at 70 ° C. (oil phase).
The oil phase was added to the water phase, pre-emulsified, homogenized with a homomixer, cooled to 30 ° C with good stirring,
I got a cream.

(Example 3) Cream (combination component) (% by weight) (1) Solid paraffin 5.0 (2) Beeswax 10.0 (3) Vaseline 15.0 (4) Liquid paraffin 41.0 ( 5) Glycerin monostearate polyoxyethylene (20 mol) 2.0 (6) Sorbitan monolaurate 2.0 (7) Soap powder 0.1 (8) Borax 0.2 (9) Calophyllum brasiliense extract 0.05 (Methanol extract) (10) Cleome hassleriana extract (Methanol extract) 0.05 (11) Sodium bisulfite 0.03 (12) Ethyl paraben 0.3 (13) Flavor appropriate amount (14) Ion Exchange water residue (Production method) Add (7) and (8) to (14) and heat to 7
It was kept at 0 ° C. (aqueous phase). On the other hand, (1) to (6), (9)
(13) was mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase while stirring to carry out a reaction. After completion of the reaction, the mixture was uniformly emulsified with a homomixer, cooled to 30 ° C. while stirring well after emulsification, and a cream was obtained.

(Example 4) Emulsion (combination component) (% by weight) (1) 2.5 stearic acid (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" (9) Myrcia sphaerocarpa extract (methanol extract) 0.01 (10) Sodium bisulfite 0.01 (11) Ethyl paraben 0.3 (12) Appropriate amount of perfume (13) Residual ion exchange water (Production method) (8) was dissolved in a small amount of (13) (phase A).
On the other hand, (6) and (7) were added to the remaining (13), and the mixture was dissolved by heating and maintained at 70 ° C. (aqueous phase). (1) to (5),
(9) to (12) were mixed, melted by heating, and kept at 70 ° C. (oil phase). The oil phase was added to the water phase, preliminarily emulsified, the phase A was added, and the mixture was uniformly emulsified with a homomixer. After the emulsification, the mixture was cooled to 30 ° C. while stirring well to obtain an emulsion.

(Example 5) Emulsion (combination component) (% by weight) (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) Annona muricata extraction (Ethanol extract) 1.0 (10) Sodium bisulfite 0.01 (11) Ethylparaben 0.3 (12) Appropriate amount of perfume (13) Ion-exchanged water residue (Production method) (13) And heated and maintained at 70 ° C. (aqueous phase). On the other hand, (1) to (7), (9) to (1)
2) was mixed, heated and melted, and kept at 70 ° C. (oil phase).
The aqueous phase was gradually added to the oil phase while stirring, and the mixture was uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well to obtain an emulsion.

(Example 6) Jelly (combination component) (% by weight) (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", BF Goodrich) (5) Caustic soda 0.15 (6) L-arginine 0.1 (7) Calophyllum brasiliense extract 0.7 ( (50% ethanol aqueous solution extract) (8) Sodium 2-hydroxy-4-methoxybenzophenone sulfonate 0.05 (9) Ethylenediaminetetraacetate / 3Na / 2 water 0.05 (10) Methylparaben 0.2 (11) Perfume Amount (12) Ion-exchanged water residue (Production method) (4) was uniformly dissolved in (12) (aqueous phase).
On the other hand, (7) and (3) were dissolved in (1), and this was added to the aqueous phase. Next, (2) and (8) to (11) were added thereto, and the mixture was neutralized with (5) and (6) and thickened to obtain jelly.

(Example 7) Essence (combination component) (% by weight) (A phase) Ethyl alcohol (95%) 10.0 Polyoxyethylene (20 mol) octyldodecanol 1.0 Pantotenyl ethyl ether 0.1 Cleome hassleriana extract (acetone extract) 1.5 methyl paraben 0.15 (phase B) potassium hydroxide 0.1 (phase C) glycerin 5.0 dipropylene glycol 10.0 sodium bisulfite 0.03 carboxy Vinyl polymer 0.2 (“Carbopol 940”, BF Goodrich) Purified water residue (Preparation method) Dissolve A phase and C phase uniformly, and add A to C phase
The phases were added and solubilized. Next, after adding the phase B, the mixture was filled in a container to obtain a serum.

Example 8 Pack (combination component) (% by weight) (A phase) Dipropylene glycol 5.0 Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) Myrcia sphaerocarpa extract (Ethanol extract) 0.01 Olive oil 5.0 Tocopherol acetate 0.2 Ethyl paraben 0.2 Fragrance 0.2 (Phase C) Sodium bisulfite 0.03 Polyvinyl alcohol (degree of saponification 90, degree of polymerization 2,000) 13. 0 Ethanol 7.0 Purified water Residue (Preparation method) A phase, B phase, and C phase are each dissolved uniformly, and A
Phase B was added to solubilize. Next, after adding this to phase C, it was filled in a container to obtain a pack.

(Example 9) Solid foundation (combination component) (% by weight) (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 2.0 (11) Isocetyl octoate 2.0 (12) Annona muricata extract (ethyl acetate extract) 1.0 (13) Preservatives proper amount (14) Fragrance proper amount (Production method) (1) to (7) The powder component of (1) was sufficiently mixed with a blender, and the oil component of (8) to (11) was added thereto.
After adding 2), (13) and (14) and kneading well, the mixture was filled into a container and molded to obtain a solid foundation.

(Example 10) Emulsion type foundation (cream type) (combination component) (wt%) (powder part) titanium dioxide 10.3 sericite 5.4 kaolin 3.0 yellow iron oxide 0.8 Bengala 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 50.0 1,3- Butylene glycol 4.5 Cleome hassleriana extract 1.5 (50% aqueous ethanol extraction) Sorbitan sesquioleate 3.0 Preservatives Appropriate amount Flavors Appropriate amount The body was added and homomixed. Further, the oil phase mixed by heating was added, and the mixture was subjected to a homomixer treatment. Then, a flavor was added with stirring, and the mixture was cooled to room temperature to obtain an emulsified foundation.

Each of the cosmetics of Examples 1 to 10 is excellent in collagenase activity inhibitory effect.

[0054]

As described above, the preparation of the present invention
Has an excellent collagenase activity inhibitory effect, prevents collagen degradation by collagenase, retains fibers, maintains elastic, wrinkle-free and slack-free skin, and prevents skin aging. It can prevent / improve and maintain youthful skin condition.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Masahiro Ota 1050 Nippa-cho, Kohoku-ku, Yokohama, Kanagawa Prefecture Inside Shiseido Daiichi Research Center Co., Ltd. Inside Shiseido Daiichi Research Center Co., Ltd. (72) Inventor Motoyoshi Satake 2-2-24 Mizuhiki, Atsugi, Kanagawa Prefecture 4C083 AA082 AA111 AA112 AA122 AB032 AB152 AB212 AB232 AB242 AB352 AB432 AC012 AC022 AC072 AC092 AC102 AC122 AC172 AC182 AC242 AC252 AC342 AC402 AC422 AC432 AC442 AC472 AC482 AC532 AC542 AC582 AD042 AD092 AD112 AD152 AD162 AD512 AD1212 CC07 CC08 MA28 MA63 ZA89 ZC20

Claims (1)

[Claims] [1] An Aspergillus rein (Annona muricata)
L.), Calophyllum br.
asiliense Cambess.), Cleome Hasleliana (Cleo)
a collagenase activity inhibitor comprising one or more plants selected from the group consisting of C. me hassleriana Chodat.) and Milkia sphaerocarpa (Myrciasphaerocarpa DC.), or a solvent extract thereof.