JPH1017461A - Preparation for external use for improving skin roughness - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a highly safe skin roughness-improving preparation for external use, having excellent effects for improving and preventing various kinds of skin diseases, skin roughness, rough skins, etc., by compounding the extract of Sophora flavescens Aiton. SOLUTION: This preparation for external use for improving skin roughness contains the solvent extract of a perennial plant, Sophora flavescens Aiton, as an active ingredient in an amount of 0.0005-20wt.%, preferably 0.001-10wt.%, based on the whole amount of the preparation for external use as a dry product. The extract is especially obtained by immersing or thermally refluxing the roots of the Sophora flavescens Aiton in a solvent (e.g. 1,3-butyleneglycol), filtering and subsequently concentrating the filtrate. Ointments, creams, milky lotions, lotions, packs, bath articles, etc., can be prepared by conventional methods. The skin roughness-improving preparation for external use especially exhibits an inhibiting activity against serine protease as a protease-inhibiting agent. The preparation is effective for skin roughness caused by various kinds of skin diseases such as contact dermatitis and psoriasis, the skin roughness of healthy person, rough skins, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD [0001] The present invention improves the skin roughness and roughness of healthy people by adding a solvent extract of Clara, in addition to the rough skin symptoms caused by various skin diseases such as contact dermatitis and psoriasis. The present invention relates to an external preparation for preventing rough skin having a preventive effect.

[0002]

2. Description of the Related Art Various therapeutic agents, external preparations for the skin, cosmetics, and the like have been conventionally known as having an effect of improving and preventing skin diseases and rough skin. In these conventional drugs and cosmetics, as active ingredients, amino acids and polysaccharides having high anti-inflammatory effect, or moisturizing effect, lipids, extract extracts, etc.,
It has been used because of its excellent ability to prevent skin inflammation and loss of water in the stratum corneum. However, in any case, the effect of improving and preventing rough skin is not always sufficient, and the development of more excellent medicinal agents has been expected. on the other hand,
In recent years, it has been revealed that proteases are involved in the formation of disease images of various skin diseases. For example, in psoriasis, which is representative of inflammatory dyskeratosis, high plasminogen activator (Plasminiog) is present in the affected epidermis.
en activator: PA) Activity has been observed. PA is one of the serine proteases.
Report the presence of strong PA activity, especially at the site of parakeratosis in the psoriatic epidermis (Arch. Klin. Exp. Dermatol; 234,196).
9), Fraki and Hopsu-Havu extracted PA activity from psoriatic scales using a highly concentrated salt solution (Arc
h. Dermatol. Res; 256,1976). In addition, in pemphigus vulgaris, a large amount of PA synthesized in epidermal cells converts plasminogen (Plasminogen) present outside the cells into plasmin (Plasmin), which digests intercellular binding substances. It has been revealed in an in vitro experimental system that tissue fluid accumulates between cells to form intraepidermal blisters (Morioka S. et al: J. Inves).
t. Dermatol; 76, 1981). Proteases are also thought to play an important role in normal keratinization of the epidermis such as stratum corneum formation (Ogawa H., Yoshiike
T .: Int. J. Dermatol; 23, 1984), and attempts have been made to use protease inhibitors as a skin improving agent or a therapeutic agent for skin diseases.

[0003]

SUMMARY OF THE INVENTION In view of the above situation, the present inventors consider that protease activity inhibitors are effective in improving various skin diseases, rough skin, roughness, and the like. As a result of examining the protease inhibitory activity, it was found that the solvent extract of Clara had trypsin-type serine protease inhibitory activity.
Furthermore, it has been found that the plant extract extremely effectively improves proliferative skin thickening, erythema, dryness, and rough skin accompanied by desquamation. The present inventors have completed the present invention based on the above findings.

The solvent extract of Clara has long been known to have excellent pharmacological effects on bitter stomach, analgesia, antipyresis, etc. In particular, since decoction exhibits excellent medicinal properties on the skin, it is chronic. It has been used externally for eczema and the like, and in recent years, reports on tyrosinase inhibitory action and hyaluronidase inhibitory action have been reported (Japanese Patent Application Laid-Open No. 60-1040).
No. 05, JP-A-1-128933). Also,
The present applicant has previously found that Clara extract has an effect of inhibiting proteases produced by microorganisms considered to be resident in skin epidermis and preventing inflammation involving resident bacteria such as acne. (Japanese Unexamined Patent Publication No. 1-12893)
No. 4). However, there has been no report on the skin roughness improving effect of Clara extract, and no application to a skin roughness improving agent has been known.

That is, the present invention relates to Clara (scientific name: Sophor
a flavescens Aiton).

Hereinafter, the configuration of the present invention will be described in detail. Clara (scientific name: Sophora flaves) used in the present invention
cens Aiton), also known as Kujin, is a perennial plant widely distributed in Japan, the Korean Peninsula and China. The extract used in the present invention is the roots, leaves,
It is obtained by immersing or heating and refluxing the whole plant such as bark, stem, fruit and the like together with an extraction solvent, followed by filtration and concentration, and a root extract is particularly preferable. The extraction solvent used in the present invention is not particularly limited as long as it is a solvent usually used for extraction. In particular, an organic solvent such as alcohols such as methanol and ethanol, aqueous alcohols, acetone, and ethyl acetate is used alone or in combination. Can be.

The amount of the Clara extract in the present invention is 0.0005-20.
0% by weight, preferably 0.001 to 10.0% by weight. If the amount is less than 0.0005% by weight, the effects of the present invention cannot be sufficiently exerted. Further, even if the content is 10.0% by weight or more, the effect is not so much improved.

The external preparation for improving skin roughness according to the present invention can be applied as a protease inhibitor. Protease, a protease inhibitor, is a general term for enzymes that catalyze the hydrolysis of peptide bonds, and these proteases are classified into peptidases and proteinases. The former is from outside the amino terminal or carboxyl terminal of the peptide chain.
It is an enzyme that breaks peptide bonds, and the latter is an enzyme that breaks specific bonds inside peptide chains. The latter proteinases are further roughly classified into four types, serine, cysteine, aspartic acid, and metal, depending on the type of active catalytic group, and each has a specific inhibitor. The protease inhibitor according to the present invention is characterized in that it exhibits an inhibitory activity particularly on serine protease. In addition, the protease of the present invention is present (produced) in the skin, and when it is increased, it is a factor that causes one factor such as rough skin. The external preparation for improvement has an action of inhibiting the protease in the skin.

The external preparation for improving skin roughness according to the present invention includes, in addition to the above essential components, components usually used in external preparations for skin such as cosmetics and pharmaceuticals, for example, whitening agents, moisturizing agents, antioxidants,
An oil component, an ultraviolet absorber, a surfactant, a thickener, an alcohol, a powder component, a coloring material, an aqueous component, water, various skin nutrition agents, and the like can be appropriately compounded as needed.

In addition, 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 derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid and the like Other whitening agents, sugars such as glucose, fructose, mannose, sucrose, trehalose and the like can also be appropriately compounded.

The external preparation for improving skin roughness of the present invention may be any of those conventionally used in external preparations for skin, such as ointments, creams, emulsions, lotions, packs, bath preparations and the like, and the dosage form is not particularly limited.

[0012]

Next, the present invention will be described in more detail by way of examples. Note that the present invention is not limited by this. The compounding amount is% by weight. Prior to the examples, a test method and a result of the plant extract of the present invention relating to protease inhibitory effect and skin roughness improving effect will be described.

1. Protease inhibitory effect test The inhibitory activity on plasmin and trypsin was evaluated as two representative serine proteases.

(1) Preparation of Sample 50 g of Clara root was immersed in 1,3-butylene glycol for 1 week at room temperature, and the extract was concentrated to obtain 1.5 g of 1,3-butylene glycol extract. Was. This extract was dissolved in DMSO at 1%, the concentration was adjusted by diluting this solution, and the following experiment was performed using this.

(2) Measurement of plasmin inhibitory activity The percent inhibition was determined by the fibrin plate method. That is, 0.
Veronal buffer containing 1% plasminogen-depleted fibrinogen (25 m with 0.125 M NaOH)
M sodium barbitalate aqueous solution, pH 7.4) 6 m
1M into a 9cm φ Petri dish, and 0.1M-CaC
a l ₂ 0.2ml and 25U / ml of thrombin 0.1m
1 and gently mixed, and left for 1 hour. On a plate formed by converting fibrinogen to fibrin, 5 U / ml plasmin and a test substance were mixed at 29: 1.
Was kept at 37 ° C. for 10 minutes, 20 μl of the mixture was added, and the dish was left at 37 ° C. for 18 hours. The same operation was performed using DMSO instead of the test sample as a control, and then the area of a dissolved circle formed by dissolution of fibrin was measured.

[0016]

## EQU1 ## Inhibition rate (%) = 1- (dissolution circle area of test sample /
Control dissolution circle area)

Thus, the plasmin inhibition rate was determined. Table 1 shows the results.

(3) Measurement of trypsin inhibitory activity The inhibitory rate was determined using casein as a substrate. That is, 2m
1 g of phosphate buffer was dissolved in 40 μg of trypsin, and 0.1 M phosphate buffer containing 6.0% casein (p.
0.9 ml of H7.4) and 0.1 ml of a test sample were added, and the mixture was kept at 37 ° C. for 10 minutes. Thereafter, 3 ml of 5% trichloroacetic acid was added, and the mixture was allowed to stand at room temperature for 1 hour.
After centrifugation at 0 rpm for 15 minutes, the absorbance at 280 mμ of the supernatant was measured. Note that the above operation is performed in Test
(T) Control (C) in which the order of addition of trypsin was changed after that of trichloroacetic acid, and Standard in which DMSO was added instead of the test sample.
(S), the order in which the addition of trypsin of Standard was changed after adding trichloroacetic acid was defined as Blank (B), and the following formula was used:

[0019]

## EQU2 ## Inhibition rate (%) = 1- (TC / SB)

Thus, the trypsin inhibition rate was determined. Table 1 shows the results.

As a reference example, ginger (Zingiberac), a plant already known to be applied to rough skin, is used as a reference.
eae) Kunit (scientific name: Curcuma d)
omestica) and an ethanol extract of mugwort were also subjected to the same test as described above. Table 1 also shows the results.

[0022]

[Table 1] ──────────────────────────────── Inhibition rate (%) Sample addition concentration 添加プ ラ ス Plasmin trypsin ──────────────────────────────── Clara extract 0.1% 38.8 35.4 0.01% 19.7 18.6 Kunit 0.1% 3.0 0 0.01% 0 0 Artemisia 0.1% 18.6 0 0.01% 5.8 0 ────

2. Skin roughness improvement effect test (1) Practical use test The effect of the external preparation of the present invention applied to the skin was evaluated based on the improvement rate against skin roughness, razor loss and pigmentation, and skin irritation. Using the face of a panel of 60 women suffering from rough skin, of a lotion having the composition (% by weight) shown in Table 2, a sample was applied to one of the left and right cheeks, and a control was applied to the other cheek twice a day for 2 weeks. After application, the skin condition was visually determined. A lotion having the composition shown in Table 2 was applied to 30 male panels who lost the razor immediately after shaving, and the effect on razor losing was determined.
Each criterion was as follows. As a sample, two kinds of samples of the present invention which differ in the concentration of Clara 1,3-butylene glycol extract were used. As a comparative product, ginger (Zi), a plant already known to be applied to rough skin, was used.
ngiberaceae) Kunit (scientific name: C)
urcuma domestica) and ginger (Zingiberaceae)
Department of Lempuyang (scientific name: Zingiber
(Methanol extract of aromaticum Mal.) was used. The results are also shown in Table 2.

Judgment Criteria for Improvement Effect on Skin Roughness Significant Effect: Elimination of symptoms. Effective: those with reduced symptoms. Somewhat effective: Somewhat weakened symptoms. Ineffective: No change in symptoms.

Judgment Criteria for Improvement Effect on Razor Loss Significant effect: Loss of razor loss. Effective: Razor loser weakened. Somewhat effective: Razor losing slightly weakened. Invalid: No change in razor loss.

Improvement effect on rough skin and razor losing A: The proportion (effective rate) at which the subject shows remarkably effective, effective and slightly effective (effective rate) is 80% or more. ：: The proportion (effective rate) at which the test subject shows a remarkable effect, an effective effect and a somewhat effective effect is 50% or more and less than 80%. Δ: The ratio (effective rate) at which the test subject showed remarkable, effective, and somewhat effective (effective rate) was 30% or more and less than 50%. ×: The ratio (effective rate) at which the subject exhibited significant, effective, and somewhat effective (effective rate) was less than 30%.

Skin irritation ◎: 0% of subjects had a burning sensation on the skin. ：: The proportion of subjects who felt tingling on the skin was less than 5%. Δ: The ratio of subjects who felt burning on the skin was less than 10%. ×: The proportion of subjects who felt burning on the skin was 10% or more.

[0028]

[Table 2] ──────────────────────────────── Sample of the present invention Comparative sample ─────── １ 1 1 1 2 ク ラ Clara 1,3-butylene glycol extraction Product 1.0 0.5 − − Kunit Methanol extract − − 1.0 − Rempuyan Methanol extract − − − 1.0 Glycerin 10.0 10.0 10.0 10.0 1,3-butylene glycol 4.0 4.0 4.0 4.0 Ethanol 7.0 7.0 7.0 7.0 Polyoxyethylene (20 mol) Oleyl alcohol 0.5 0.5 0.5 0.5 Purified water Residual Residual Residual Residual 改善 Skin roughness improvement effect ○ ○ △ △ Razor loss prevention effect ◎ ○ △ △ Skin irritation ◎ ◎ ○ △ ────────────────── ──────────────

As is apparent from Table 2, the sample of the present invention containing the Clara extract showed a more improved effect on rough skin and razor losing than the sample of the comparative product, and also showed skin irritation. I couldn't.

(2) Actual use test by replica method Using lotions of the present invention products 1 and 2 and comparative products 1 and 2,
A skin roughness improvement effect test was performed using a human body panel. That is, the replica of the skin surface of a healthy female person (face) was sampled using a replica method with a millisin resin, and a microscope (17) was used.
Times). Based on the criteria shown in Table 3, the skin roughness evaluation was 1 or 2 based on the state of the skin pattern and the peeled state of the stratum corneum.
The lotions of the products 1 and 2 of the present invention and the comparative products 1 and 2 were applied to the left and right half of the face twice a day for 2 weeks using 20 persons judged to be "poor skin". Two weeks later, the skin condition was observed again according to the replica method described above, and evaluated according to the criteria shown in Table 3. Table 4 shows the results.

[0031]

[Table 3] 点 Scoring criteria for scoring ─────── １ 1 Skin sulcus, skin ridges disappeared, and widespread stratum corneum was observed. 2 Skin groove and skin ridges are unclear and horny layer is turned up. 3 Skin sulcus and skin ridge are recognized, but flat. 4 Skin sulcus and skin hills are clear. 5 Skin grooves and skin ridges are clear and well-organized. ─────────────────────────────────

[0032]

[Table 4] 評 価 Replica evaluation Product of the present invention 1 Product of the present invention 2 Comparative product 1 Comparison Article 2 １ 100 1 111 2 0 2 3 2 3 8 9 9 14 11 14 10 9 2 6 5 2 0 0 0 ─────────────────────────────────

As can be seen from Table 4, the lotion of the product of the present invention showed a remarkable effect of improving rough skin as compared with the lotion of the comparative product.

Hereinafter, examples of various formulations of external preparations for improving skin roughness according to the present invention will be described as examples.

Example 1 Cream (Formulation) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Clara extract 0.01 Caustic potash 0.0 2 Sodium bisulfite 0.01 Preservatives Appropriate amount Fragrance Appropriate amount Ion-exchanged water Residue (Preparation method) Add propylene glycol, Clara extract and caustic potash to ion-exchanged water, dissolve and heat to 70 ° C (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is maintained for a while to cause a reaction. Thereafter, the mixture is uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

Example 2 Cream (Formulation) Stearic acid 2.0% by weight Stearyl alcohol 7.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl alcohol ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 Clara extract 0.05 Sodium bisulfite 0.03 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water Residue (Production method) Add propylene glycol to ion-exchanged water ,
Heat and maintain at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase, pre-emulsified, homogenized with a homomixer, and cooled to 30 ° C. with good stirring.

Example 3 Cream (Formulation) Solid paraffin 5.0% by weight Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monolaurate 2 0.0 Soap powder 0.1 Borax 0.2 Clara extract 0.1 Sodium bisulfite 0.03 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchanged water Residue (Production method) Add soap powder and borax to ion-exchanged water and heat and dissolve And maintain at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After completion of the reaction, the mixture is uniformly emulsified with a homomixer, and cooled to 30 ° C. while stirring well after emulsification.

Example 4 Emulsion (Formulation) Stearic acid 2.5% by weight Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (Product name: Carbopol 941, BFGoodrich Chemical c
ompany) Clara extract 0.01 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water residue (Preparation method) Dissolve carboxyvinyl polymer in a small amount of ion-exchanged water (phase A). Polyethylene glycol 1500 and triethanolamine are added to the remaining ion-exchanged water, dissolved by heating, and kept at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase to perform preliminary emulsification, the phase A is added, and the mixture is uniformly emulsified with a homomixer. After the emulsification, the mixture is cooled to 30 ° C. while stirring well.

Example 5 Emulsion (Formulation) Microcrystalline wax 1.0% by weight Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 mol) ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Clara extract 10.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Appropriate amount Ion-exchanged water Residue (Production method) Add propylene glycol to ion-exchanged water,
Heat and maintain at 70 ° C. (aqueous phase). The other components are mixed, heated and melted and kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added thereto, and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C with good stirring.

Example 6 Jelly (Formulation) 95% ethyl alcohol 10.0% by weight Dipropylene glycol 15.0 Polyoxyethylene (50 mol) oleyl alcohol ether 2.0 Carboxyvinyl polymer 1.0 (Product name: Carbopol) 940, BFGoodrich Chemical company) Caustic soda 0.15 L-arginine 0.1 Clara extract 7.0 Sodium 2-hydroxy-4-methoxybenzophenonesulfonate 0.05 Ethylenediaminetetraacetate trisodium 2 water 0.05 Methylparaben 0 .2 Perfume Appropriate amount Ion-exchanged water Residue (Preparation method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while Clara extract and polyoxyethylene (50 mol) oleyl alcohol ether are dissolved in 95% ethanol. To be added. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 7 Serum (Prescription) (Phase A) Ethyl alcohol (95%) 10.0% by weight Polyoxyethylene (20 mol) octyldodecanol 1.0 Pantothenyl ethyl ether 0.1 Clara extract 1 0.5 methyl paraben 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 (trade name: Carbopol 940, BFGoodrich Chemical company) Purified water residue (Preparation method) Dissolve A phase and C phase uniformly, and add A to C phase
Add phases and solubilize. Next, after adding the phase B, filling is performed.

Example 8 Pack (Formulation) (A phase) 5.0% by weight of dipropylene glycol Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) Clara extract 0.01 Olive oil 5.0 Acetic acid Tocopherol 0.2 Ethylparaben 0.2 Fragrance 0.2 (Phase C) Sodium bisulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, Polymerization degree 2,000) Ethanol 7.0 Purified water residue (Production method) A phase, B phase, and C phase are each dissolved uniformly,
Add phase B to phase and solubilize. Next, this is added to the C phase and then filled.

Example 9 Solid foundation (formulation) Talc 43.1% by weight Kaolin 15.0 Sericite 10.0 Zinc white 7.0 Titanium dioxide 3.8 Yellow iron oxide 2.9 Black iron oxide 0.2 Squalane 8 0.0 Isostearic acid 4.0 POE sorbitan monooleate 3.0 Isocetyl octoate 2.0 Clara extract 1.0 Preservatives Appropriate amount Fragrance Appropriate amount (Preparation method) Thorough mixing of talc and black iron oxide powder components in a blender, The oily components of squalane to isocetyl octanoate, Clara extract, preservative, and fragrance are added to the mixture, kneaded well, and the mixture is filled into a container and molded.

Example 10 Emulsion Type Foundation (Cream Type) (Prescription) (Powder Part) Titanium Dioxide 10.3% by Weight 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 Clara Extract 1.5 Sorbitan sesquioleate 3.0 Preservatives Appropriate amount Flavors Appropriate amount (Preparation method) After heating and stirring the aqueous phase, a well-mixed and pulverized powder portion is added, followed by homomixer treatment. Further, the oil phase mixed by heating is added, and the mixture is treated with a homomixer. Then, a fragrance is added with stirring, and the mixture is cooled to room temperature.

[0045]

As described above, the external preparation for improving skin roughness according to the present invention is excellent in improving skin roughness, and has excellent effects in improving and preventing various skin diseases, skin roughness, roughness and the like. It is also excellent in safety.

Claims (2)

[Claims] [Claim 1] Clara (scientific name: Sophora flavescens Ait
An external preparation for improving skin roughness, which comprises a solvent extract of on). 2. The external preparation for improving rough skin according to claim 1, which is a protease inhibitor present in the skin.