JP2003034644A - Hyaluronidase inhibitor and skin care composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin care composition which is capable to prevent and improve skin troubles such as allergic dermatitis, supersensitive-sensitive skin, and also effective for preventing aging of the skin, by formulating an extract of plant having excellent antiallergic action, antiinflammatory action and superoxide dimustase action in view of safety to the skin and effects. SOLUTION: The extract of Simmondsia chinensis (Schneider 1907) possesses high activity for inhibiting hyaluronidase activity and excellent safety to the skin, and the skin care composition being formulated with this extract prevents and improves dermatitis caused by allergy and ultraviolet rays.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a hyaluronidase inhibitor, an anti-allergic action, and prevention of oxidative stress caused by reactive oxygen species, skin damage caused by ultraviolet rays, and the like.
It relates to an external composition for skin that can be improved.

[0002]

2. Description of the Related Art Urticaria, contact dermatitis, atopia due to increased stress in social life, including the effects of environmental scientific substances due to recent changes in eating habits, changes in lifestyle and deterioration of various environmental conditions, etc. Skin diseases involving allergic reactions such as dermatitis are increasing. Allergic reactions are classified into type I to type IV. IgE antibodies are mainly involved in the type I allergic reaction. IgE antibodies are produced against foreign antigens, IgE antibodies are fixed to mast cells and basophils, and sensitization is established. When antigens are contacted again, antigen-antibody reaction occurs in the sensitized cells, resulting in histamine. , A chemical messenger such as serotonin is released, which causes various vascular permeabilities, edema, smooth muscle contraction, and various allergic symptoms. IgG and IgM antibodies are involved in the type II allergic reaction. When an antibody binds to an antigen cell, cell destruction occurs by chain-activating the proteins that form the complement system to form a complex that destroys the cell membrane. When anaphylatoxin is excessively generated in the process of activation of the complement system, vascular permeability is enhanced, smooth muscle is contracted, histamine is released, and various allergic symptoms occur. IgG antibodies are mainly involved in the type III allergic reaction. Onset is said to occur by a complex mechanism involving many factors such as the complement system and polymorphonuclear leukocytes. Sensitization T for type IV allergy
It is caused by the reaction between lymphocytes and an antigen. Previous I-III
Although the type is immediate type, it is a delayed type reaction, and external contact substances such as allergic contact dermatitis are absorbed from the skin and cause an eczema reaction in conformity with the contact site.

In the treatment of allergic diseases, antiallergic drugs such as drugs having a cell membrane stabilizing effect on mast cells, drugs suppressing the production or release of chemical mediators, or drugs having an antagonistic effect on chemical mediators, The application of symptomatic drugs such as choline drugs, antihistamines, xanthines, sympathomimetics, and steroids is being studied.

On the other hand, for external skin preparations such as cosmetics, there is a high demand for anti-allergic agents that have high safety and mild action, and can be used for daily skin care. Derived glycyrrhizin derivatives have been mainly used. Also, in combination with the improvement of natural orientation, screening of antiallergic agents originating from plants has been actively carried out, and Vladivostok (Japanese Patent Laid-Open No. 6-239757), Engosaku (Japanese Patent Laid-Open No. 7-10764), and Lauraceae plants (JP-A-7-10765), Hibiscus (JP-A-9-87)
188), pomegranate (Japanese Unexamined Patent Publication No. 9-110710), dog caterpillar (Japanese Unexamined Patent Publication No. 9-263526), plants of the genus Juzudama / Dokudamiaceae plant (Japanese Unexamined Patent Publication No. 10-120583), sesame and forsythia (Japanese Unexamined Patent Publication No. 11-180885). The ingredient is disclosed as the active ingredient.

However, some of the conventional antiallergic agents have local irritation, mucosal irritation, etc., and have side effects as represented by antihistamines. Also, among plant-based anti-allergic agents,
There are problems in that sufficient effects cannot be obtained, and there are many problems of color and odor that hinder formulation, and it is difficult to obtain a product of constant quality.

Therefore, the object of the present invention is to allergize by incorporating a plant extract having an excellent anti-allergic action, anti-inflammatory action and active oxygen species elimination action as a cosmetic additive from the aspects of skin safety and effect. The purpose of the present invention is to provide a highly safe external preparation for external use / bath which is effective in preventing and improving skin troubles such as sexual skin disease, hypersensitivity and sensitive skin, and preventing skin aging.

[0007]

In view of such circumstances, the inventors of the present invention have widely used in the natural world a substance which is excellent in antiallergic or antiinflammatory action, has no dermatological side effect, and has a palliative effect on the skin. As a result of diligent studies on existing plants, the inventors have found that the extract of jojoba leaves has a high inhibitory effect on hyaluronidase activity and completed the present invention.

The jojoba used in the present invention has a scientific name of Simm.
ondsia chinensis (Schneide
r1907), which is a plant that grows naturally in the arid regions of the southwestern United States (Arizona, California) and northern Mexico (Sonora, Baja). It is now domesticated and cultivated in dry areas such as the United States, Mexico, Israel, Argentina and Australia. Up to now, seed oil has been mainly used as a cosmetic oil in jojoba. Regarding the use of jojoba leaves, the present inventors have studied the active oxygen suppressing action of jojoba leaf extract and the external composition for skin containing these (JP-A-2000-1541).
35). However, the hyaluronidase activity inhibitory action and anti-allergic / anti-inflammatory effect of the extract from jojoba leaves have not been known at all.

Although the main body of the hyaluronidase activity inhibitor contained in the jojoba leaf extract of the present invention has not been confirmed yet, it is presumed to be a polyphenol compound. Jojoba leaves used for the extraction of jojoba leaves having this high hyaluronidase activity inhibitory activity, if necessary, use raw or dried ones as they are or crushed, and organically grown leaves can be used as well. . Examples of the extraction method include a method of using various suitable solvents and performing extraction at room temperature or under heating.

Specific examples of the extraction solvent include water, lower monohydric alcohols such as methanol and ethanol, glycerin,
Propylene glycol, dipropylene glycol, 1,
Liquid polyhydric alcohols such as 3-butylene glycol and lower alkyl esters such as ethyl acetate are exemplified, and one or more of these mixed solvents can be used.
It is preferable to use water, ethanol, 1,3-butylene glycol or a mixture thereof.

The jojoba leaf extract of the present invention can inhibit high hyaluronidase activity even if the extract obtained as described above is used as it is, but it can also be used as a concentrated concentrate of the obtained extract. it can. It can also be used as an extract powder by operations such as spray drying and freeze drying. In addition, column chromatography,
Those purified by countercurrent partition chromatography or the like can be used. The method for processing and purifying the extract is not limited.

The content of the jojoba leaf extract, which is an essential component of the external composition for skin according to the present invention, is not limited in any way, but is 0.0001 to 5.0 in terms of dry solid matter.
% By weight (hereinafter referred to simply as "%"), preferably 0.
001 to 3.0% is preferable.

The external preparation for skin of the present invention contains, in addition to the above-mentioned essential components, surfactants, oils and fats, polyhydric alcohols, lower alcohols, thickeners, ultraviolet absorbers / scatterers which are generally used as cosmetic ingredients. Agents, preservatives, antioxidants, chelating agents, pH adjusters, fragrances, dyes and the like can be appropriately added. Specific examples of these additive components are as follows.

As the surfactant, a base material for soap, fatty acid soap, higher alkyl sulfate ester, alkyl ether sulfate salt, N-acyl sarcosinic acid, higher fatty acid amide sulfonate, phosphate ester salt, sulfosuccinate, alkylbenzene. Sulfonate, N-acyl glutamate, higher fatty acid ester sulfate ester salt, sulfated oil, POE alkyl ether carboxylate, POE
Alkyl allyl ether carboxylate, α-olefin sulfonate, higher fatty acid ester sulfonate, secondary alcohol sulfate ester salt, higher fatty acid alkylolamide sulfate ester salt, lauroyl monoethanolamide succinate salt, N-palmitoyl aspartic acid Anionic surfactants such as ditriethanolamine and sodium caseinate. Alkyl trimethyl ammonium salt, dialkyl dimethyl ammonium salt, alkyl pyridium salt, alkyl quaternary ammonium salt, alkyl dimethyl benzyl ammonium salt, alkyl isoquinonium salt, dialkyl morphonium salt, POE alkyl amine, alkyl amine salt, polyamine fatty acid derivative , Cationic surfactants such as amyl alcohol fatty acid derivatives, benzalkonium chloride and benzethonium chloride. Amphoteric surfactants such as imidazoline-based surfactants and betaine-based surfactants. Lipophilic nonionic surfactants such as sorbitan fatty acid ester, glycerin fatty acid ester, propylene glycol fatty acid ester, hydrogenated castor oil derivative, glycerin alkyl ether, and polyoxyethylene / methylpolysiloxane copolymer. POE sorbitan fatty acid ester, POE sorbitol fatty acid ester, POE glycerin fatty acid ester, POE fatty acid ester, POE alkyl ether, POE alkyl phenyl ether, POE / POP
Alkyl ether, tetra POE / tetra POP ethylenediamine condensate, POE hydrogenated castor oil derivative, POE
Beeswax lanolin derivative, alkanolamide, PO
Examples include hydrophilic nonionic surfactants such as E propylene glycol fatty acid ester, POE alkyl amine, POE fatty acid amide, and sucrose fatty acid ester.

The oils include avocado oil, olive oil,
Sesame oil, camellia oil, evening primrose oil, turtle oil, macadamian nut oil, corn oil, mink oil, rapeseed oil, egg yolk oil, persic oil, wheat germ oil, southern oil, castor oil, linseed oil, safflower oil, cottonseed oil, Eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, tung oil,
Animal and vegetable oils such as jojoba oil, cacao butter, palm oil, horse oil, palm oil, palm kernel oil, beef tallow, sheep fat, lard, lanolin, spermaceti, beeswax, carnauba wax, mokuro, candelilla wax, squalane, and its hardening. oil. Mineral oil such as liquid paraffin and petrolatum. There are synthetic triglycerins such as glycerin tripalmitate.

Examples of the higher fatty acid include lauric acid,
Examples include myristic acid, palmitic acid, oleic acid, linoleic acid, linolenic acid, stearic acid, behenic acid, 12-hydroxystearic acid, isostearic acid, undecic acid, tallic acid, eicosapentaenoic acid, and docosahexaenoic acid. Examples of higher alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol,
Oleyl alcohol, cetostearyl alcohol, jojoba alcohol, lanolin alcohol, batyl alcohol, 2-decyltetrathecesinol, cholesterol,
Examples include phytosterol and isostearyl alcohol. Examples of synthetic esters include cetyl octanoate, octyldodecyl myristate, isopropyl myristate, myristyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate,
Decyl orenic acid, dimethyl octanoic acid, cetyl lactate,
Examples include myristyl lactate. Examples of silicones include chain polysiloxanes such as dimethylpolysiloxane and methylphenylpolysiloxane, cyclic polysiloxanes such as decamethylcyclopolysiloxane, and those having a three-dimensional network structure such as silicone resin.

Examples of moisturizers include glycerin, propylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, hexylene glycol, xylitol, sorbitol, maltitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, atelocollagen. , Urea, sodium lactate,
In addition to bile salts, dlpyrrolidone carboxylates, soluble collagen, and the like, there are various animal and plant extracts, yeast extracts and the like.

Examples of the ultraviolet absorbers include benzoic acid type ultraviolet absorbers such as paraaminobenzoic acid and paraaminobenzoic acid derivatives, anthranilic acid type ultraviolet absorbers such as homomenthyl-N-acetylanthranilate, and salicylic acid type absorbers such as amyl salicylate. UV absorbers, cinnamic acid-based UV absorbers such as octylcinnamate, benzophenone-based UV absorbers such as 2,4-dihydroxybenzophenone, 4-methylbenzylidene camphor, 3-benzylidene camphor, 2-phenyl-5-methylbenzoxa There are sols.

Examples of vitamins include vitamin A such as vitamin oil and retinol, vitamin B2 such as riboflavin, and vitamin B6 such as pyridoxine hydrochloride.
, Vitamin Cs such as L-ascorbic acid, pantothenic acids such as calcium pantothenate, vitamin Ds such as ergocalciphenol, nicotinic acids such as nicotinamide, vitamin Es such as tocophenol acetate, vitamin P, biotin Etc.

Examples of the natural water-soluble polymer include gum arabic, tragacanth gum, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, agar, quince seed, algae colloid, starch,
Examples include xanthan gum, dextran, succinoglucan, pullulan, collagen, casein, hyaluronic acid, albumin and gelatin. Examples of the semi-synthetic water-soluble polymer include cellulosic polymers such as methylcellulose, nitrocellulose and sodium carboxymethylcellulose, starch-based polymers such as carboxymethylstarch, and alginic acid-based polymers such as sodium alginate. Examples of the synthetic water-soluble polymer include vinyl polymers such as polyvinyl alcohol and carboxyvinyl polymer, polyoxyethylene polymers such as polyethylene glycol 2000, and copolymer polymers such as polyoxyethylene polyoxypropylene copolymer. System, acrylic polymer such as polyacrylamide, polyethyleneimine, cationic polymer and the like.

As the powder component, for example, talc, kaolin, mica, sericite, magnesium carbonate, calcium carbonate, silicate, silica, barium sulfate, burnt gypsum, fluoroapatite, inorganic powder such as ceramic powder, nylon powder, Examples include organic powders such as polyethylene powder, polystyrene powder, and cellulose powder. As the coloring agent, inorganic pigments such as titanium dioxide, iron oxide, carbon black and cobalt violet, organic pigments such as red 201, red 3, yellow 205 and yellow 4, chlorophyll, riboflavin, β-carotene, etc. Natural pigments, plant extract pigments such as safflower and turmeric. Preservatives include benzoate, salicylate, sorbate, dehydroacetate, paraoxybenzoate, benzalkonium chloride, hinokitiol, resorcin, ethanol and the like. Examples of antioxidants include tocophenol, ascorbic acid, butylhydroxyanisole, dibutylhydroxytoluene, and gallic acid ester. Examples of the chelating agent include sodium ethylenediaminetetraacetate, sodium polyphosphate, citric acid and the like.

Further, plant extracts having physiologically active actions such as antibacterial activity, cell activation, moisturizing, sebum secretion control, anti-inflammatory, astringent, anti-oxidant, whitening, suppression of active oxygen, anti-allergic, etc., and their extracted fractions and purified products Can also be used together. Also,
In addition to the above, fragrance, alcohol, water and the like can be appropriately added.

The external preparation composition for skin containing the hyaluronidase activity inhibitor of the present invention is not limited to general skin cosmetics, but includes pharmaceuticals, quasi drugs, cosmeceuticals and the like. The dosage form of the skin external preparation composition of the present invention may be any of a solubilizing system, an emulsifying system, a powder dispersion system, and the like, and is also used for makeup such as lotions, emulsions, creams, basic cosmetics such as packs and foundations. Cosmetics, shampoo, conditioner, soap, toiletries such as body shampoo, and bath agents can be used.

Next, examples will be described, but the present invention is not limited to these examples.

(Production Example 1) 100 g of dried jojoba leaves
Was added to 3 kg of a 50 vol% ethanol solution, and the mixture was extracted with stirring at 50 ° C. for 8 hours, cooled, filtered, concentrated and freeze-dried to obtain 8.5 g of extract powder A.

(Production Example 2) 20 kg of a 50 vol% ethanol solution was added to 1 kg of dried jojoba leaves, and the mixture was extracted with stirring at 60 ° C. for 8 hours, filtered after cooling, and then concentrated to obtain a synthetic adsorbent DIAION HP-. Pass through a column filled with 20. After washing with water, 10 vol% ethanol solution, 20 v
ol% ethanol solution, 30 vol% ethanol solution,
Elution with a 50 vol% ethanol solution, the resulting washing solution and each eluate were concentrated and dried to obtain extract powder B6.
1.5 g, extract powder C 7.24 g, extract powder D 7.54
g, extract powder E5.73 g, and extract powder F4.9 g were obtained.

(Production Example 3) 200 g of dried jojoba leaves
Then, 4 kg of 50 vol% ethanol solution is added, and the mixture is extracted with stirring at 60 ° C. for 8 hours, cooled, filtered, concentrated, and passed through a column filled with octadecylsilylated silica gel for column chromatography. After washing with water, the fractions eluted with a 10 to 30 vol% ethanol solution were combined, concentrated under reduced pressure, and
It was freeze-dried to obtain 3.8 g of the extract powder G.

Test Example 1 Measurement of Hyaluronidase Activity Inhibitory Effect Hyaluronidase is a hydrolase of hyaluronic acid distributed in connective tissue, and is activated during inflammation, destroys the connective tissue matrix, and inflames cells. And is believed to play a role in increasing the permeability of blood vessels. It is also known as a respiratory enzyme and is also known to be inhibited by anti-inflammatory agents and antiallergic agents. Therefore, the hyaluronidase activity inhibitory action is considered to be one of the antiallergic activities.

(Test Method) Each extract powder shown in the production example was dissolved in purified water to a concentration of 0.5% to prepare a sample. As a positive control, sodium cromoglycate (manufactured by Fujisawa Pharmaceutical Co., Ltd.) whose inhibitory activity was already known was used in the test. The test method was performed by applying the Morgan-Elson method.

An appropriate amount of sample was added to 0.1 M acetate buffer (pH
Hyaluronidase (Type IV, S manufactured by Sigma, Type IV · S, final enzyme activity is 400 NFunit / mL) 0.1 mL was added to 0.2 mL of the solution diluted with 3.5), and the mixture was allowed to stand at 37 ° C. for 20 minutes and then the activity was reached. Co as an agent
Add 0.2 mL of acetate buffer solution (0.1 mg / mL) of mound48 / 80 (manufactured by Sigma), and further add 3
Leave for 20 minutes at 7 ° C. Potassium hyaluronate (Wako Pure Chemical Industries) solution (final concentration 0.4 mg / m
L) Add 0.5 mL and leave at 37 ° C. for 40 minutes.
Next, on ice, 0.4m sodium hydroxide solution 0.2m
After L was added to stop the reaction, boric acid solution (boric acid 4.95 g, water 50 mL was added, and the pH was adjusted to 9.1 with 1N sodium hydroxide solution), and water was added to 100 m.
L) 0.2 mL was added, and after mixing, 3 in a boiling water bath.
Heat for a minute to inactivate the enzyme. Next, the mixture was cooled to room temperature on ice, and p-dimethylaminobenzaldehyde reagent (manufactured by Wako Pure Chemical Industries, Ltd., 10 g of 10N hydrochloric acid solution 12.5 mL and acetic acid 87.5 mL was mixed and dissolved, and 10% with acetic acid immediately before use.
6 mL is added and the mixture is allowed to stand at 37 ° C. for 20 minutes, and then the absorbance is measured at 585 nm. It should be noted that the one containing acetate buffer instead of the sample solution was used as a control, and each sample solution and control were blank without enzyme, and the inhibitory activity rate was calculated by the following formula, and the sample concentration was adjusted to 50%. The inhibitory activity concentration (IC ₅₀ ) was determined. Inhibition rate (%) = [1- (absorbance of sample solution−absorbance of sample solution blank) / (absorbance of control solution−absorbance of control solution blank)] × 100

(Test Results) As shown in Table 1, it was confirmed that the jojoba leaf extract has a high hyaluronidase activity inhibitory action. Moreover, although the inhibitory activity was lower than that of known sodium cromoglycate, the antiallergic effect was sufficiently expected.

[0032]

[Table 1]

(Test Example 2) Panel test-1 For 30 women aged 20 to 39 years old (average age 24.8 years old) having mild atopic skin symptoms, the skin external composition of Table 2 was applied for 1 day. Table 2 also shows the evaluation of the results of application and application on the face for two consecutive months (morning and evening). The evaluation was based on the following criteria. Effective: Redness and itchiness due to inflammation and rough skin were improved Moderately effective: Redness and itchiness due to inflammation and rough skin were improved Ineffective: No change from before use

[0034]

[Table 2]

(Test Example 3) Panel test-2 50 healthy females aged 20 to 35 (average age 24.2)
Table 3 shows the results obtained by applying the external preparation for skin used in Panel Test-1 twice a day (morning and evening) to the face for 3 consecutive months, and using the same for 3 months. The sensory evaluations were four items: moisturizing, texture, wrinkles, and sunburn stains / freckles.

[0036]

[Table 3]

As is clear from Tables 2 and 3, the use of the external skin solution containing the agent for inhibiting the activity of the jojoba leaf extract-derived hyaluronidase of the present invention has an excellent effect of improving the inflammation of the skin, In addition, it was confirmed that the skin-improving effect and the effect of preventing spots and freckles due to ultraviolet rays.

Test Example 4 Skin Safety Test 30% of the jojoba leaf extract powder A shown in Production Example 1 was prepared.
Liquid dissolved in butylene glycol solution (solid content 1.0
%) Was used as the test solution. The primary skin irritation test is
As a result of using 3 New Zealand White rabbits, the skin primary irritation index was 0.0. Sequential skin irritation test was performed using Dunkin Hartl of 3 males and 3 females.
As a result of continuous repeated administration for 14 days using the ey-type guinea pig, the maximum weekly average stimulation index was 0.0, and it was determined that there was no stimulation. The eye irritation test was carried out on the eyes of three New Zealand White rabbits, and the maximum group average score was 0.0, which was determined to be non-irritating. For the skin sensitization test, white guinea pigs were subjected to the Adjuvant / Patch method,
10 test animals and 10 control animals each with an expression rate of 0 /
In No. 10, it was confirmed that there was no sensitization. Phototoxicity and photosensitization tests are conducted by Dunkin Hartley.
When used with 5 guinea pig females each, it did not cause any signs of phototoxicity or photosensitization. From these skin safety results, it is clear that the jojoba leaf extract of the present invention is very safe in terms of skin safety.

(Test Example 5) Patch test Two males and two females aged 20 to 51 (average age 26.3)
Forty healthy volunteers consisting of 0 were used. As the test substance, the liquid used in the skin safety test and the external composition for skin B used in the panel test were used, and 30% 1,3-butylene glycol solution and physiological saline were used as controls. The test was a 24-hour closed coating test. Using a human-body patch test fin chamber (diameter 11 mm, Taisho Pharmaceutical Co., Ltd.), 0.1 mL of each test substance was applied, and then immediately applied to the back of the test subject and left for 24 hours. Then, the fin chamber was removed 24 hours later, and the skin reaction was observed 30 minutes later and the next day (48 hours later) according to the criteria.

The judgment criteria were in accordance with those of the Japanese Patch Test Study Group. No reaction ・ ・ ・ ・ (−) Slight erythema ・ ・ ・ ・ (±) Clear erythema ・ ・ ・ ・ (+) Erythema + swelling ・ ・ ・ ・ (++) Erythema + swelling + papules or small vesicles ・ ・ ・・ （＋＋＋） Large water bubbles ・ ・ ・ ・ ・ ・ （＋＋＋＋）

The test results are shown in Table 4. None of the cases showed a positive reaction (+ or more). In addition, in each sample group, 30% 1,3-
The frequency was almost the same as that in the case of butylene glycol solution or saline. Therefore, the skin irritation was judged to be low, and it was revealed that there is no problem in terms of safety when incorporated into an external skin preparation.

[0042]

[Table 4]

Example 1 Cream The following components (1) to (10), and separately the following components (11) to
(15) is dissolved by heating at 75 ° C. to prepare solutions A and B, respectively. Solution B is added to solution A to emulsify, stirring at 50 ° C
The mixture was cooled to room temperature and ingredient (16) was added to prepare a cream. (Component) (% by weight) (1) Jojoba oil 3.0% (2) Squalane 2.0% (3) Methylpolysiloxane 0.5% (4) Stearyl alcohol 0.5% (5) Cetyl alcohol 0. 5% (6) Tri (capryl glyceryl caprate 12.5% (7) Glyceryl monostearate 5.0% (8) Diglyceryl monostearate 1.5% (9) Decaglyceryl monostearate 3.0 % (10) Propyl paraoxybenzoate 0.1% (11) Xanthan gum 0.1% (12) Jojoba leaf extract powder A (Production Example 1) 0.05% (13) 1,3-Butylene glycol 5.0% (14) Methyl paraoxybenzoate 0.2% (15) Purified water 66.0% (16) Perfume 0.05%

(Example 2) Lotion The following components (5) to (8) were mixed and dissolved to prepare a liquid A. Separately, the following components (1) to (4) and (9) were mixed and dissolved to prepare liquid B. As a liquid, the liquids A and B were evenly mixed to prepare a lotion. (Component) (% by weight) (1) Quinceseed extract 8.0% (2) Glycerin 3.0% (3) 1,3-Butylene glycol 5.0% (4) Jojoba leaf extract (*) 2.0 % (5) Polyoxyethylene sorbitan lauric acid ester 1.2% (6) Ethyl alcohol 5.0% (7) Methyl paraoxybenzoate 0.2% (8) Perfume 0.1% (9) Purified water 75. 5%

(Example 3) Emulsion The following components (1) to (10) and (11) to (14) and (16) were separately dissolved by heating at 75 ° C to prepare solutions A and B, respectively, Add Liquid B to emulsify and stir 5
It cooled to 0 degreeC and added the component (15), and prepared the emulsion. (Components) (% by weight) (1) Jojoba oil 1.0% (2) Squalane 2.0% (3) Behenyl alcohol 1.0% (4) Tri (capryl glyceryl caprate 2.0%) (5) Tetra Glycerin-condensed silinoleic acid 0.1% (6) Propylene glycol monooleate 0.5% (7) Glycerin monostearate 1.0% (8) Hexaglyceryl monomyristate 1.0% (9) Decaglyceryl monomyristate 0.5% (10) Propyl paraoxybenzoate 0.1% (11) Quinceseed extract 5.0% (12) Jojoba leaf extract powder A (Production Example 1) 0.03% (13) 1,3-butylene Glycol 3.0% (14) Methyl paraoxybenzoate 0.1% (15) Perfume 0.1% (16) Purified water 82.57%

Example 4 Soap The following ingredients were mixed and produced by a standard method for producing soap.       (Component) (% by weight)   (1) Soap substrate 53.2%   (2) Scroll 19.4%   (3) Jojoba oil 0.25%   (4) Jojoba leaf extract (*) 5.0%   (5) Reduced honey solution 0.25%   (6) Concentrated glycerin 6.5%   (7) Hydroxyethanediphosphonic acid 0.15%   (8) Regular water 15.25%

(Example 5) Cleansing gel The following components (1) to (3) and separately (4) to (6) and (8) were dissolved by heating at 70 ° C to prepare liquid A and liquid B, respectively. Solution B is added to and stirred until uniform. It cooled to 50 degreeC, stirring, and the ingredient (7) was added and the cleansing gel was manufactured. (Component) (% by weight) (1) Hexaglyceryl monomyristate 20.0% (2) Liquid paraffin 59.7% (3) Paraoxybenzoic acid ester 0.3% (4) Jojoba leaf extract powder A (Production Example) 1) 0.1% (5) Concentrated glycerin 5.9% (6) Sorbitol 5.0% (7) Perfume 0.1% (8) Purified water 8.9%

Example 6 Packing Agent A phase, B phase, and C phase were uniformly dissolved, and phase B was added to phase A to solubilize it, and then phase C was added and dissolved uniformly,
To make. (Component) (% by weight) (Phase A) Dipropylene glycol 5.0% Polyoxyethylene hydrogenated castor oil 5.0% (Phase B) Olive oil 5.0% Tocophenol acetate 0.2% Paraoxybenzoic acid ester 2% (Phase C) Polyvinyl alcohol 13.0% Jojoba leaf extract (*) 3.0% Ethanol 7.0% Purified water 61.6%

(Example 7) Solid foundation The following components (1) to (7) were uniformly mixed with a blender,
(8) to (12) are added to this and kneaded well to produce. (Component) (% by weight) (1) Talc 42.6% (2) Kaolin 15.5% (3) Sericite 10.0% (4) Zinc white 7.0% (5) Titanium dioxide 3.8% (6) Yellow iron oxide 2.8% (7) Black iron oxide 0.3% (7) Black iron oxide 0.3% (8) Squalane 8.0% (9) Isostearic acid 4.0% (10) Polyoxyethylene sorbitan monooleate 3.0% (11) Isocetyl octoate 2.0% (12) Jojoba leaf extract (*) 1.0%

(Example 8) Shampoo The following ingredients are mixed by heating and uniformly.       (Component) (% by weight)   (1) N-coconut oil fatty acid glutamate triethanol 25.0%         Amine   (2) Lauric acid diethanolamide 5.0%   (3) Potassium myristate 5.0%   (4) Ethylene glycol distearate 2.0%   (5) Polyethylene glycol 400 15.0%   (6) Jojoba oil 1.0%   (7) Jojoba leaf extract (*) 3.0%   (8) Chlorxylenol 0.1%   (9) Vitamin E 0.1% (10) Paraoxybenzoic acid ester 0.2% (11) Fragrance 0.3% (12) Purified water 43.3%

Example 9 Bath Agent (Component) (wt%) (1) Dry Sodium Sulfate 40.0% (2) Sodium Bicarbonate 57.5% (3) Olive Oil 0.2% (4) Jojoba Leaf Extract powder A (Production Example 1) 0.1% (5) Light anhydrous silicic acid 0.3% (6) Fragrance 1.7% (7) Yellow No. 202 (1) 0.2% Of the above examples , Jojoba leaf extract (*)
The extract powder G (1 g) was dissolved in 100% 30% 1,3-butylene glycol solution (100 g), filtered and used.

[0052]

INDUSTRIAL APPLICABILITY As described above in detail, the jojoba leaf extract, which is the hyaluronidase activity inhibitor of the present invention, has an excellent hyaluronidase activity inhibitory action and is excellent in safety.
The external composition for skin containing this is also excellent in improving redness, itchiness and rough skin associated with inflammation.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 43/00 111 A61P 43/00 111 F term (reference) 4C083 AA082 AA111 AA112 AA122 AB212 AB232 AB242 AB312 AB352 AB372 AB432 AB442 AC022 AC072 AC102 AC122 AC132 AC242 AC262 AC342 AC392 AC422 AC432 AC442 AC472 AC642 AC662 AC892 AD042 AD112 AD152 AD352 AD512 AD662 CC02 CC04 CC05 CC12 CC25 CC38 DD31 EE10 EE12 EE13 4C088 AB12 AC05 BA08 CA04 MA17 MA28 MA63 NA14 ZA89 ZC

Claims (3)

[Claims] 1. A hyaluronidase inhibitor containing a hyaluronidase inhibitor extracted from jojoba leaves as an active ingredient. 2. A composition for external use for skin, which comprises the hyaluronidase inhibitor of claim 1. 3. The skin external preparation composition according to claim 2, which has an antiallergic effect.