JPH0920643A - External preparation for improving chapped skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an external preparation for improving chapped skin having protease inhibiting activity, improving and preventing chapped skin and suffering from chapped skin caused by various dermatoses such as contact dermatosis, psoriasis, etc. SOLUTION: This external preparation for improving chapped skin comprises 0.005-20wt.%, preferably 0.01-10wt.% calculated as a dried material of an extract of Zapote growing in a dry meadow, a pasture, etc., of South America, especially Andes based on the total of the external preparation as an active ingredient. The external preparation is properly mixed with a beautifying agent, a humectant, an antioxidant, an oily component, an ultraviolet light absorber, a surfactant, a thickening agent, an alcohol, a powder component, a colorant, an aqueous component, water, various skin neutriments, etc., besides the active ingredient, to prepare an ointment, a cream, a milky lotion, a lotion, a pack, a bathing agent, etc. The extract of Zapote is obtained by immersing the whole grass of Zapote such as leaf, stem, fruit, etc., in an extractive solvent (e.g. methanol) or heating under reflux, filtering and concentrating.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to Zapote.
The present invention relates to an external preparation for improving rough skin, which has an effect of improving / preventing rough skin and roughness of healthy persons as well as rough skin symptoms due to various skin diseases such as contact dermatitis and psoriasis.

[0002]

2. Description of the Related Art As active ingredients such as therapeutic agents, external preparations for the skin, cosmetics and the like having an effect of improving / preventing various skin diseases and rough skin, they have anti-inflammatory effects. Amino acids, polysaccharides, lipids, extract extracts, and the like, which have or have a high moisturizing effect, have been used because of their characteristic use effects. However, the effect is not always sufficient, and the development of a better drug has been expected. On the other hand, in recent years, it has been revealed that proteases are involved in the pathological formation of various skin diseases. For example, in psoriasis, which is a representative of inflammatory dyskeratosis, high plasminogen activator (PA) activity is observed in the affected epidermis. While PA is one of the serine proteases, Haustein reports that strong PA activity is present in psoriatic epidermis, especially at the site of parakeratosis (Arch. Klin. Exp.
Dermatol; 234, 1969), Fraki and Hopsu-Ha
vu extracted PA activity from psoriatic scales using a high concentration salt solution (Arch. Dermatol. Res; 256,1976). Also,
In pemphigus vulgaris, a large amount of PA synthesized in epidermal cells is converted into extracellular plasminogen (Plasmini).
gen) to plasmin, which digests intercellular binders to store interstitial fluid between cells and form blisters in the epidermis.
itro) in experimental systems (Morioka
S. et al: J. Invest. Dermatol; 76,1981). Proteases are also considered to play an important role in the normal keratinization process of the epidermis such as stratum corneum formation (Ogaw
a H., Yoshiike T .: Int. J. Dermatol; 23, 1984), and attempts have been made to use protease inhibitors as agents for improving skin or treating skin diseases.

[0003]

In view of the present situation as described above, the inventors of the present invention believe that protease activity-inhibiting substances are effective in improving various skin diseases, rough skin, rough skin, etc. As a result of investigating the protease inhibitory activity of the above, it was found that the extract of Zapote had the trypsin type serine protease inhibitory activity. Furthermore, it has been found that the plant extract very effectively improves proliferative skin thickening, erythema, dryness, and rough skin with desquamation. The present inventors have completed the present invention based on the above findings.

There has been no report on the protease inhibitory action of Zapote extract, and its application to a protease inhibitor or a rough skin improving agent has not been known at all. Further, as an example in which an extract of Zapote is mixed with an external preparation for skin, an external preparation for skin containing the plant extract as a whitening agent has only been reported by the applicant (Japanese Patent Application No. Hei 6) 168682).

That is, the present invention is directed to Zapot.
e, scientific name: Quararibea amazonia) is an external preparation for improving rough skin, which is characterized by being blended.

The structure of the present invention will be described in detail below. Zapote used in the present invention (scientific name: Quarar
ibea amazonia) is a plant that grows in South America, especially in Andean dry grasslands and pasture. The extract used in the present invention, the leaves and stems or fruits, etc., the Zapote whole grass is immersed or heated under reflux with an extraction solvent, and then filtered,
Obtained by concentrating. 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 Zapote extract in the present invention is
The total amount of the external preparation is 0.005 to 20.0% by weight, preferably 0.01 to 10.0% by weight, as a dried product. 0.
If it is less than 005% by weight, the effect of the present invention is not sufficiently exhibited, and if it exceeds 20.0% by weight, formulation is difficult, which is not preferable. 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, which is a protease inhibitor, is a general term for enzymes that catalyze the hydrolysis of peptide bonds, and this protease is 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 in the present invention is characterized by exhibiting inhibitory activity against serine protease among them.

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 oily component, an ultraviolet absorber, a surfactant, a thickener, an alcohol, a powder component, a coloring material, an aqueous component, water, various skin nutritional agents and the like can be appropriately blended as necessary.

In addition, 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 fruits of fire thorns, various crude drugs, tocopherol acetate,
Drugs such as glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate,
Other whitening agents such as ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, mannose,
Sugars such as sucrose and trehalose can also be appropriately blended.

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 Samples 50 g of stems and branches of Zapote were immersed in ethanol at room temperature for 1 week, and the extract was concentrated to obtain 3.2 g of ethanol extract. This solid was dissolved again in ethanol to prepare a 1% solution. 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, As
Prepare a fibrin plate according to the method of trup et al. (Arch. B-iochem .; 40,346,1952), and use the sample prepared as above diluted with ethanol to 0.1% and 0.01%. did. The results are shown in Table 1.

(3) Measurement of trypsin inhibitory activity Muramatu et al. (J. Bioche) using casein as a substrate.
m .; 58, 214, 1965) and the inhibition rate was determined. Samples were also diluted to 0.1% and 0.01%, and the results are shown in Table 1. In addition, as a reference example, Kunyi (Zingiberaceae), which is a plant whose application is already known for rough skin, is
t, scientific name: Curcuma domestica), ginger (Zingibera)
Lempuyang (scientific name: Zi)
ngiber aromaticum Mal.) and the ethanolic extract of mugwort were subjected to the same test as above. Table 1 also shows the results.

[0017]

[Table 1] ──────────────────────────────── Inhibition rate (%) Sample addition concentration ────── ───────── Plasmin trypsin ──────────────────────────────── Zapote 0.1% 43.7 38.4 0.01% 17.9 21.9 Khunit 0.1% 3.0 0 0.01% 0 0 Rempuyang 0.1% 0 0 0.01% 0 0 Wormwood 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 the sample of the present invention, two kinds of the present invention were prepared by changing the concentration of the methanol extract of Zapote, and as a comparative product, Kunity of the Zingiberaceae family, which is a plant whose application to rough skin has already been known, is known. : Curcuma domestic
a) and Gemp (Zingiberaceae) family Lempuyang, scientific name: Zingiber aromaticum Ma
l.) methanol extract was used. Table 3 shows the results.

Criteria for improvement effect on rough skin: Remarkable effect: symptom disappeared. Effective: those with reduced symptoms. Somewhat effective: Somewhat weakened symptoms. Ineffective: No change in symptoms.

Criteria for Improvement Effect on Razor Loss Remarkable Effect: Razor loss disappeared. Effective: Razor loser weakened. Somewhat effective: Razor losing slightly weakened. Invalid: No change in razor loss.

Improvement Effect on Rough Skin and Razor Loss ⊚: The rate at which the test subject is markedly 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 the subjects had a tingling 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.

[0023]

[Table 2] ──────────────────────────────── Inventive product Comparative product Test product ──────── ─────── 1 2 1 2 1 2 ──────────────────────────────── Zapote methanol extract 1.0 0.5 − -Khunit 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 ──────────────────────────────────

[0024]

[Table 3] ──────────────────────────────── Comparative product of the present invention Sample ──────── ─────── 1 2 1 2 1 ──────────────────────────────── Skin roughening improvement effect ○ ○ △ △ Razor loss prevention effect ◎ ○ △ △ Skin irritation ○ ◎ ○ △ ──────────────────────────────────

As is clear from Table 3, the sample of the present invention containing the Zapote extract showed an excellent effect of improving rough skin and razor loss as compared with the sample of the comparative product, and also showed skin irritation. I couldn't do it.

(2) Actual Use Test by Replica Method Using lotions of the present invention products 1 and 2 and the comparative products 1 and 2,
A human body panel was tested for the effect of improving rough skin. 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.
Doubled). Based on the criteria shown in Table 4, the rough skin evaluation is 1 or 2 based on the state of the skin pattern and the peeling 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 above-mentioned replica method, and evaluated according to the criteria shown in Table 4. The results are shown in Table 5.

[0027]

[Table 4] ───────────────────────────────── Scores Standards of scores ──────── ─────────────────────────── 1 Disappearance of skin crevices, cuticles, and wide-ranging horny layer are observed. 2 Unsmooth skin groove and crust, and horny turn of the stratum corneum. 3 There are pits and ridges, but they are flat. 4 Clear skin grooves and ridges. 5 Crusts and ridges are clear and well organized. ─────────────────────────────────

[0028]

[Table 5] ──────────────────────────────── Replica evaluation Inventive product 1 Inventive product 2 Comparative product 1 Comparative Product 2 ──────────────────────────────── 1 0 0 1 0 2 1 1 1 3 4 3 6 6 8 13 13 11 4 12 11 3 5 5 1 0 0 0 ──────────────────────────────────

As can be seen from Table 5, the lotion of the product of the present invention had a remarkable effect of improving rough skin as compared with the lotion of the comparative product.

Example 1 Cream (prescription) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Zapotemethanol extract 0.01 Caustic potash 0.2 Sodium bisulfite 0.01 Preservative Suitable amount Perfume Suitable amount Ion-exchanged water Residual (production method) Dissolve propylene glycol, Zapote methanol extract and caustic potash in ion-exchanged water and heat to 7
Keep at 0 ° C. (aqueous phase). Mix other ingredients, heat and melt.
Keep at 0 ° 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. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

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 ester 2.0 Propylene glycol 5.0 Zapote ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume suitable amount Ion exchange water Residue (production method) Propylene glycol in ion exchange water And add
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 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 (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 Zapoteacetone extract 0.05 Zapote ethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Fragrance suitable amount Ion-exchanged water Residual (production method) Soap to ion-exchanged water The powder and borax are added, melted 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 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 (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 3. 0 triethanolamine 1.0 carboxyvinyl polymer 0.05 (trade name: Carbopol 941, BFGoodrich Chemical company) Zapote acetic acid ethyl ester extract 0.01 sodium bisulfite 0.01 ethylparaben 0.3 perfume proper amount ion-exchanged water Residual (manufacturing method) The carboxyvinyl polymer is dissolved 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 wt% Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 4.0 Polyoxyethylene (20 mol) ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Zapoteacetone extract 10.0 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Perfume suitable amount Ion-exchanged water Residual (production method) Propylene glycol is added 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 (trade name: Carbopol) 940, BFGoodrich Chemical company) Caustic soda 0.15 L-Arginine 0.1 Zapote 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate ・ 3 sodium ・ 2 water 0 .05 Methylparaben 0.2 Fragrance Suitable amount Ion-exchanged water Residue (production method) Carbopol 940 was uniformly dissolved in ion-exchanged water, while Zapote 50% ethanol aqueous solution extract and polyoxyethylene (50 mol) oleyl was added to 95% ethanol. Alcohol Was dissolved ether, is added to the aqueous phase. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 7 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Weight Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Zapotemethanol Extraction Substance 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 (trade name: Carbopol 940, BFGoodrich Chemical company) Purified water Residue (production method) Phases A and C are uniformly dissolved, and A is added to phase C.
Add phases and solubilize. Next, after adding the phase B, filling is performed.

Example 8 Pack (formulation) (Phase A) Dipropylene glycol 5.0% by weight Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Zapotemethanol extract 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 13.0 (Saponification degree 90, degree of polymerization 2,000) Ethanol 7.0 Purified water Residual ( Manufacturing method) A phase, B phase, and C phase are uniformly dissolved, respectively.
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 octanoate 2.0 Zapote ethanol extract 1.0 preservative appropriate amount perfume appropriate amount (production method) Talc to black iron oxide powder components are thoroughly mixed with a blender. Then, an oily component of squalane to isocetyl octoate, a Zapote ethanol extract, an antiseptic, and a fragrance are added and kneaded well, and then 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 The Potato ethanol extract 1.5 Sorbitan sesquioleate ester 3.0 Preservative proper amount Perfume proper amount (Production method) The aqueous phase is heated and stirred, and then the powder portion thoroughly mixed and pulverized is added to perform 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.

[0040]

INDUSTRIAL APPLICABILITY As described above, the external preparation for improving rough skin of the present invention has an excellent effect of improving rough skin, and also has an excellent effect of improving / preventing various skin diseases, rough skin, roughness and the like. It is also excellent in safety.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Hirohiko Sakamoto 1050 Nippa-cho, Kohoku-ku, Yokohama-shi, Kanagawa Inside Shiseido Daiichi Research Center Co., Ltd.

Claims (2)

[Claims] 1. Zapote (scientific name: Quararib)
An external preparation for improving rough skin, which is characterized by containing an extract of ea amazonia). 2. The amount of the Zapote extract compounded is 0.005.
The external preparation for improving rough skin according to claim 1, which is 20.0% by weight.