JP5155543B2 - Endothelin-1 production inhibitor, hexosaminidase release inhibitor, anti-inflammatory / whitening skin preparation, endothelin-1 production inhibition method, and hexosaminidase release inhibition method - Google Patents

Description

  The present invention relates to an endothelin-1 production inhibitor and a hexosaminidase release inhibitor, which are useful as active ingredients for external preparations for skin such as cosmetics. The present invention also relates to an anti-inflammatory and / or whitening skin external preparation, a method for suppressing the production of endothelin-1, and a method for suppressing the release of hexosaminidase.

  Conventionally, for the purpose of imparting prescribed medicinal effects to skin external preparations such as emulsions, creams, lotions, packs, cleaning agents, dispersions, ointments, solutions, aerosols, patches, poultices, liniments, etc. Various medicinal ingredients are added. In recent years, various causes of skin troubles have been elucidated, and along with this, consumer needs for external preparations for skin, particularly cosmetics, are being subdivided. For example, the causes and onset mechanisms of inflammatory diseases such as contact dermatitis (rash), psoriasis, pemphigus vulgaris, and other skin diseases associated with skin irritation are diverse. As one of them, one caused by secretion of endothelin-1 and one caused by release of hexosaminidase are known. Therefore, it is desired to provide an agent capable of preventing or improving skin inflammation and pigmentation caused by these causes.

On the other hand, since the safety to the skin is also important as an active ingredient to be blended in the external preparation for skin, various plant extracts that are agents derived from natural products have been proposed as active ingredients for external preparations for skin. Yes. For example, a moisturizing agent composed of a human lizard extract has been proposed (Patent Document 1).
Japanese Patent No. 3696862

It is an object of the present invention to provide a novel endothelin-1 production inhibitor and hexosaminidase release inhibitor that are highly safe for the skin and are useful as active ingredients for external preparations for skin.
Another object of the present invention is to provide an anti-inflammatory skin external preparation excellent in anti-inflammatory effect and a whitening skin external preparation excellent in whitening effect.
Another object of the present invention is to provide a novel method for suppressing the production of endothelin-1 and a novel method for suppressing the release of hexosaminidase.

In order to solve the said subject, this invention provides the endothelin-1 production inhibitor which uses a human lysizuka extract as an active ingredient, and the hexosaminidase release inhibitor which uses a human lysizuka extract as an active ingredient.
From another point of view, according to the present invention, by supplying an anti-inflammatory skin external preparation containing human lizard extract as an active ingredient; skin whitening preparation containing white lizard extract as an active ingredient; A method for inhibiting endothelin-1 production; and a method for inhibiting the release of hexosaminidase by supplying a human lysizuka extract.

  ADVANTAGE OF THE INVENTION According to this invention, the novel agent and novel method which can suppress the production | generation of endothelin-1 and the novel method and novel method which can suppress the release | release of hexosaminidase can be provided. Moreover, according to this invention, the anti-inflammatory skin external preparation excellent in the anti-inflammatory effect and the whitening skin external preparation excellent in the whitening effect can be provided.

Hereinafter, the present invention will be described in detail. In the present specification, “to” means a range including numerical values before and after.
The endothelin-1 production inhibitor and the hexosaminidase release inhibitor of the present invention contain an extract of the genus Chloranthus japonicus (scientific name: Chloranthus japonicus) as an active ingredient. There is no restriction | limiting about an extraction site | part, and the extract of any parts, such as a root, stem, a leaf, an inflorescence, a fruit, and a seed of a human lizardfish, may be sufficient as the human lizard extract used for this invention. In addition, the endothelin-1 production inhibitor and hexosaminidase release inhibitor of the present invention may be mixed with an extract obtained from two or more places of human lysizuka, or may be mixed with different solvents from two or more parts. Two or more kinds of extracted extracts may be mixed and used.

  The human squirrel extract is obtained by extracting one or two or more parts such as roots, stems, leaves, inflorescences, fruits, and seeds of the squirrel with a suitable solvent, and distilling off the solvent. These portions may be subjected to an appropriate treatment such as drying, chopping, pressing, or fermentation, followed by an extraction treatment or the like. Extraction can be carried out by immersing human lizard in a solvent at a low temperature or under heating for a predetermined time. The extraction solvent is not particularly limited, but water or lower monohydric alcohols such as methyl alcohol and ethyl alcohol; liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol; ketones such as acetone; ethyl ether and the like 1 type or 2 types or more of these ethers; Esters, such as ethyl acetate, etc., and the mixed solvent of these and water can be used.

  The human squirrel extract may be used as it is in a skin external preparation, or may be used after being left to stand for an appropriate period and aged. If necessary, it can be used after further purification treatment such as filtration, deodorization and decolorization with an ion exchange resin or the like within a range not affecting the effect. Further, only a fraction having a high activity can be used by using a separation means such as liquid chromatography.

  As an example of a preferred method for preparing the human squirrel extract, human squirrel is used by using an alcoholic solvent such as water-containing or non-hydrated ethyl alcohol, or a polyhydric alcohol solvent such as water-containing or non-hydrated 1,3-butylene glycol There is a method of performing extraction for 1 to 5 days at room temperature or warming, followed by filtration, allowing the obtained filtrate to stand for about one week and aging, and then filtering the filtrate again.

Examples of the components in the extract include flavonoid glycosides, phenols, amino acids, triterpenes and the like. The higher the content of the alcohol solvent or polyhydric alcohol solvent in the extraction solvent, the higher the triterpene content.
The extract of human squirrel extract used in the endothelin-1 production inhibitor or hexosaminidase release inhibitor of the present invention preferably has an extraction solvent that is a mixed solvent of water and a monohydric alcohol. A mixed solvent is more preferable, and a mixed solvent of water and ethyl alcohol in which the mixing ratio of ethyl alcohol is 50% by volume (hereinafter referred to as “vol%”) or more is further preferable.

  The human lizard extract can be used as an extract, dried by spray drying or the like, or in a powder form, or a dry solid or powder mixed with an appropriate solvent according to the intended use. That is, it may be used as an active ingredient of an endothelin-1 production inhibitor or a hexosaminidase release inhibitor in any form such as liquid, paste or gel.

There are a wide variety of causes and onset mechanisms of inflammatory diseases such as contact dermatitis (rash), psoriasis, pemphigus vulgaris, and other skin ailments. Those caused by the production of 1 and those caused by the release of hexosaminidase are known.
Endothelin-1 is a 21 amino acid peptide synthesized in vascular endothelial cells. Endothelin-1 secreted from vascular endothelial cells first binds to the endothelin receptor of smooth muscle cells and causes vasoconstriction. On the other hand, endothelin-1 binds to the endothelin receptor in the vascular endothelial cell itself and causes vasoconstriction. As a result, prostaglandin I2, prostaglandin E1, and thromboxanthin B2 are produced and cause inflammation. On the other hand, endothelin is also secreted from human epidermal cells upon exposure to ultraviolet rays, but it has been shown to be involved in melanin pigment production since it exhibits melanocyte growth promotion and melanin synthesis promotion action. Therefore, the skin external preparation containing the endothelin-1 production inhibitor of the present invention showing an excellent endothelin-1 production inhibitory action exhibits an excellent anti-inflammatory action and / or whitening action on the skin.
On the other hand, hexosaminidase is a kind of chemical transmitter released by leukocytes. There are many different causes and onset mechanisms of inflammatory diseases such as contact dermatitis (rash), psoriasis, pemphigus vulgaris, and other skin disorders associated with rough skin. It has been. Since it is released simultaneously with the allergic causative substance histamine, the hexosaminidase release inhibitory effect is considered as one index of the type I allergy inhibitory effect. Therefore, the skin external preparation containing the hexosaminidase release inhibitor of the present invention showing an excellent hexosaminidase release inhibitory action exhibits an excellent anti-inflammatory action on the skin.

  The endothelin-1 production inhibitor and hexosaminidase release inhibitor of the present invention can be used for various applications. Since the safety to the skin is good, it is preferably blended into the external preparation for skin. In addition, the endothelin-1 production inhibitor and hexosaminidase release inhibitor of the present invention can be blended in foods (including beverages). Although it does not restrict | limit especially as said foodstuff, Specifically, a salmon, chewing gum, a drink etc. are mentioned, for example.

Next, the skin external preparation of the present invention will be described in detail.
The skin external preparation of the present invention is a skin external preparation containing the endothelin-1 production inhibitor or hexosaminidase release inhibitor of the present invention. Although there is no restriction | limiting in particular about the compounding quantity of the said agent, The said human lizard extract is 0.00005-1.5 mass% as solid content with respect to the total mass of the skin external preparation which is a final form (henceforth, only "% It is preferable that it is 0.0005 to 1.5%. If it is within this range, the component can be stably blended, and a high endothelin-1 production inhibitory action and / or hexosaminidase release inhibitory action is brought about, and a high anti-inflammatory action based thereon is exhibited. Can do. In addition, when the extract is used, the concentration of the extract is not limited as long as the content of the human squirrel extract as a solute is within the above range.

  The form of the external preparation for skin according to the present invention is not particularly limited. Any form of cosmetic, such as a liniment, may be an external medicine.

  In addition to the radical scavenger, the skin external preparation of the present invention includes various components that are usually used in cosmetics, quasi-drugs, external medicines, ie, water, alcohols, oils, surfactants, Viscosity, powder, chelating agent, pH adjuster, UV absorber, extracts from animals and plants / microorganisms, various medicinal agents such as moisturizers, whitening agents, anti-inflammatory agents, cell activators, fragrances, etc. As long as the effect is not impaired, it can be added as appropriate.

  The present invention also relates to a method for inhibiting the production of endothelin-1 and a method for inhibiting the release of hexosaminidase by supplying a human squirrel extract. Endothelin-1 may be supplied to a system where production or hexosaminidase is already released, or they may be supplied to a non-production or non-free system. For example, it can be applied to the surface of the skin to suppress the production of endothelin-1 in the body tissue or the release of hexosaminidase to improve the condition of the skin, more specifically, It may be used to prevent or ameliorate inflammation and pigmentation. It can be used for the purpose of improving the appearance of the skin, that is, cosmetic purposes, by preventing or improving skin inflammation and pigmentation.

Hereinafter, the present invention will be described more specifically with reference to examples. However, the scope of the present invention is not limited to the following examples.
[Example 1: Manufacture of 80 vol% hydrous ethyl alcohol extract of human lizards]
150 g of 80 vol% hydrated ethyl alcohol (the ratio of ethyl alcohol is 80 vol%) is added to 10 g of human squirrel whole plant, extracted at room temperature or heated for one day, filtered, and the solvent in the obtained filtrate is filtered. Distilled to dryness, an 80 vol% water-containing ethyl alcohol extract (yield 0.8 g) of human lizards as a solid content was obtained.

[Example 2: Example of production of human lizardka 50 vol% hydrous ethyl alcohol extract]
150 g of 50 vol% hydrated ethyl alcohol (the ratio of ethyl alcohol is 50 vol%) is added to 10 g of human squirrel whole plant, extracted at room temperature or heated for one day, filtered, and the solvent in the obtained filtrate is filtered. Distilled to dryness to obtain a 50 vol% water-containing ethyl alcohol extract (yield: 0.75 g) of human lizards as a solid content.

[Example 3: Manufacture of human lizard extract]
150 mL of purified water is added to 10 g of the whole plant of human lizard, and after extraction for one day at room temperature or warming, the mixture is filtered, and the solvent in the obtained filtrate is evaporated to dryness to obtain a solid content. A purified human water extract (yield 0.73 g) was obtained.

[Example 4: Evaluation of endothelin-1 production inhibitory effect]
Human normal neonatal skin epidermal keratinocytes (NHEK) were cultured using human normal neonatal epidermal keratinocyte medium (KGM), and then cells were collected by trypsin treatment. The collected cells were diluted with KGM to a concentration of 1.0 × 10 ⁵ cells / mL, then seeded at 2 mL per well on a 6-well plate, and cultured overnight. After completion of the culture, the medium was removed, washed with 1 mL of Hanks buffer, and replaced with 1 mL of the same buffer. Ultraviolet UV-B was irradiated at 30 mJ / cm ² using an ultraviolet irradiation device equipped with four TOREX FL20SE-30 / DMR as a light source. Immediately after irradiation, the buffer solution was removed, and each test sample prepared by dissolving each of the human lysizuka extract obtained above in KGM was added to each well and cultured for 48 hours. In addition, the cells that were not irradiated with ultraviolet light and the test sample was not added were cultured under the same conditions. After completion of the culture, the amount of endothelin-1 produced in the culture supernatant was measured by ELISA.
As a result, the amount of endothelin-1 in each culture supernatant of UV-irradiated / no test sample added, UV-irradiated / test sample-added and UV-irradiated / test sample-added was quantified. When the amount of endothelin-1 was taken as 100, the ratio of the production amount of ultraviolet irradiation / no test sample addition and ultraviolet irradiation / test sample addition (endothelin-1 production rate) was calculated. The calculation method of endothelin-1 production inhibitory action is as follows.
Endothelin-1 production inhibition rate (%) = {(A−B) / (A−100)} × 100
A: Endothelin-1 production rate at the time of ultraviolet irradiation / no test sample addition B: Endothelin-1 production rate at the time of ultraviolet irradiation / test sample addition In addition, as each test sample, the aqueous solution (concentration is 5 microgram / mL) of a human lysizuka extract Was used.

[Example 5: Evaluation of hexosaminidase release inhibitory effect]
<Test method>
Rat basophil leukemia cells (RBL-2H3) were cultured using 15% FBS-added S-MEM, and then cells were collected by trypsin treatment. The collected cells are diluted with a medium to a concentration of 4.0 × 10 ⁵ cells / mL, added to a final concentration of 0.5 μg / mL of DNP-specific IgE, and then seeded at 100 μL per well on a 96-well plate, Cultured overnight. After completion of the culture, the medium was removed, and washing was performed twice with 500 μL of Siraganian buffer. Next, 30 μL of the same buffer solution and 10 μL of a sample prepared by dissolving each of the human lysizuka extract obtained in the same buffer solution were added, and the mixture was allowed to stand at 37 ° C. for 10 minutes. Thereafter, 10 μL of a 100 ng / mL DNP-BSA solution was added and the mixture was allowed to stand at 37 ° C. for 15 minutes to release hexosaminidase. Thereafter, the release was stopped by allowing the 96-well plate to stand on ice. 10 μL of the cell supernatant of each well and 10 μL of 1 mmol / L p-NAG (p-nitrophenyl N-acetyl-β-D-glucosaminide) solution were added to a new 96-well plate and reacted at 37 ° C. for 1 hour. It was. After completion of the reaction, 250 μL of a 0.1 mol / L Na ₂ CO ₃ / NaHCO ₃ mixed solution was added to each well, and the absorbance at a wavelength of 415 nm was measured. As a blank test, the absorbance at a wavelength of 415 nm of a 10 μL cell supernatant and a 250 μL mixture of 0.1 mol / L Na ₂ CO ₃ / NaHCO ₃ was measured and corrected. The calculation method of the hexosaminidase release inhibitory action is as follows.
Inhibition rate of hexosaminidase release (%) = {1− (BC) / A} × 100
A: Absorbance at a wavelength of 415 nm when no test sample is added B: Absorbance at a wavelength of 415 nm when a test sample is added C: Absorbance at a wavelength of 415 nm when a test sample is added and p-NAG is not added As a sample solution, a human lysizuka extract Was used (concentration: 0.4 mg / mL).

[Example 6: Cream]
Creams having the compositions shown in Table 3 below were prepared by the following methods.
First, components (1) to (6) and (9) shown in Table 3 were mixed, heated and maintained at 70 ° C. A part of component (11) heated to 70 ° C. was added to this mixture to emulsify, and (7) to (8) and (10) dissolved in the remainder of (11) were mixed. Then, it cooled and each cream was obtained.

(Test method)
A panel of 15 females aged 27 to 53 years per test cream, and an appropriate amount of the test cream was applied to the face after washing the face twice a morning and night for 12 weeks. The whitening and skin beautifying effects by application were evaluated according to the following criteria, and the number of people corresponding to each evaluation criterion is shown in Table 3.
(Evaluation criteria)
<Evaluation><Contents>
Effective Skin dullness is not noticeable.
Slightly effective Skin dullness is less noticeable.
Invalid No change before use.

(Composition and results)

  From the results shown in Table 3, the creams of the products 1 and 2 of the present invention formulated with 80 vol% water-containing ethyl alcohol extract and 50 vol% water-containing ethyl alcohol extract of the human lizards were applied to the skin. It became clear that it was possible to prevent and improve “dullness” and the like, and to make the skin beautiful.

Hereinafter, examples of blending into cosmetics will be shown, but not limited to these prescriptions.
[Example 7: Cleansing cream]
(Ingredient) (%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 3.0
(3) Lipophilic glyceryl monostearate 2.0
(4) Beeswax 1.5
(5) Vaseline 6.0
(6) Liquid paraffin 40.0
(7) Dimethylpolysiloxane (100CS) 0.5
(8) Sorbitan sesquioleate 1.0
(9) Preservative appropriate amount (10) Triethanolamine 1.0
(11) Propylene glycol 10.0
(12) Polyethylene glycol 20000 0.5
(13) Carboxyvinyl polymer 0.05
(14) Purified water Residual amount (15) Human vol. 50 vol% hydrous ethyl alcohol extract * 1 0.5
(16) Apple extract * 2 0.5
(17) Prune extract * 3 0.5
(18) Fragrance Appropriate amount * 1: What was obtained by dissolving the extract produced in Example 2 in 50 vol% hydrous 1,3-butylene glycol to a content of 1% * 2: Maruzen Pharmaceutical Co., Ltd. * 3: Maruzen Pharmaceutical Co., Ltd. Made (Manufacturing method)
A. Ingredients (1) to (9) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (10) to (14) are dissolved by heating and maintained at 70 ° C.
C. A is added to B and emulsified.
D. After cooling C, components (15) to (18) were added and mixed to obtain a cleansing cream.
The obtained cleansing cream was a mild cleansing cream that spreads lightly and has good makeup removal, prevents skin inflammation and pigmentation, and maintains healthy skin.

[Example 8: Face wash]
(Ingredient) (%)
(1) Lauric acid 5.0
(2) Myristic acid 18.5
(3) Stearic acid 6.0
(4) Glycerin 12.0
(5) Polyethylene glycol 1500 5.0
(6) Potassium hydroxide 6.5
(7) Purified water remaining amount (8) Palm oil fatty acid diethanolamide 5.0
(9) Palm oil fatty acid methyl taurine sodium 1.8
(10) Polyoxyethylene (7.5E.O.) lauryl ether 2.0
(11) Ethylene glycol distearate 1.0
(12) Hydroxypropyl methylcellulose 1% aqueous solution 5.0
(13) Hitori-Sizuka 50vol% hydrous ethyl alcohol extract * 1 0.5
(14) Hop extract * 2 0.5
(15) Chamomile extract * 3 0.5
(16) Fragrance Appropriate amount * 1: What was obtained by dissolving the extract produced in Example 2 in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 2: Koei Kogyo Co., Ltd. * 3: Maruzen Pharmaceutical Co., Ltd. Company (production method)
A. Components (1) to (7) are dissolved by heating.
B. Components (8) to (11) are dissolved by heating.
C. Add B to A and mix.
D. After cooling C, components (12) to (16) are added and mixed to obtain a face wash.
The obtained cleansing cream and facial cleanser had a fine and rich foaming and a refreshing feeling of use, and it was a facial cleanser that prevented skin inflammation and pigmentation and maintained healthy skin. .

[Example 9: Lotion 1]
(Ingredient) (%)
(1) Citric acid 0.05
(2) Sodium citrate 0.2
(3) Sodium pyrrolidonecarboxylate (50%) solution * 1 0.5
(4) Glycerin 3.0
(5) 1,3-butylene glycol 8.0
(6) L-ascorbic acid 2-glucoside * 2 2.0
(7) Sodium hydroxide 0.25
(8) Hitorishizuka 50vol hydrous ethyl alcohol extract * 3 1.0
(9) Perilla extract * 4 1.0
(10) Peony extract * 5 1.0
(11) Purified water remaining amount (12) Ethyl alcohol 10.0
(13) Perfume Appropriate amount (14) Preservative Appropriate amount (15) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
* 1: Ajinomoto Co., Inc. * 2: Hayashibara Biochemical Laboratories Co., Ltd. * 3: The extract produced in Example 2 dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 4 : Made by Maruzen Pharmaceutical * 5: Made by Maruzen Pharmaceutical (Manufacturing method)
A. Components (1) to (11) are mixed and dissolved.
B. Components (12) to (15) are mixed and dissolved.
C. B was added to A and mixed to obtain a skin lotion.
The obtained lotion 1 had a fresh and refreshing feeling of use, was a lotion that prevented skin inflammation and pigmentation, kept the skin fresh and smoothed the skin.

[Example 10: Lotion 2]
(Ingredient) (%)
(1) Meadow home oil 0.1
(2) Jojoba oil 0.05
(3) Perfume appropriate amount (4) preservative appropriate amount (5) polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(6) Isostearic acid polyoxyethylene hydrogenated castor oil (50 EO) 1.0
(7) Ethyl alcohol 8.0
(8) Glycerin 5.0
(9) 1,3-butylene glycol 5.0
(10) Polyethylene glycol 1500 0.1
(11) Hitorishizuka 80vol% hydrous ethyl alcohol extract * 1 1.0
(12) Dipotassium glycyrrhizinate * 2 0.5
(13) Rosemary extract * 3 0.5
(14) Remaining amount of purified water * 1: The extract produced in Example 1 was dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1%. * 2: Maruzen Pharmaceutical Co., Ltd. * 3: Maruzen Made by Pharmaceutical Company (Manufacturing method)
A. Components (1) to (7) are mixed and dissolved.
B. Components (8) to (14) are mixed and dissolved.
C. A is added to B and mixed to obtain a skin lotion.
The obtained lotion 2 had a fresh and mellow feeling of use, was a lotion that prevented skin inflammation and pigmentation, kept the skin fresh and smoothed the skin.

[Example 11: Lotion 3]
(Ingredient) (%)
(1) Glyceryl tri-2-ethylhexanoate 0.08
(2) Squalane 0.02
(3) Sorbitan sesquioleate 0.05
(4) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.05
(5) Polyoxyethylene (8E.O.) alkylene (12-15)
Ether phosphoric acid 0.1
(6) Preservative appropriate amount (7) perfume appropriate amount (8) ethyl alcohol 8.0
(9) Dipropylene glycol 8.0
(10) Glycerin 4.0
(11) Hitori Shizuka 80vol% hydrous ethyl alcohol extract * 1 0.5
(12) Sodium hyaluronate 1% aqueous solution * 2 3.0
(13) Mallow extract * 3 0.5
(14) Purified water remaining amount * 1: The extract produced in Example 1 was dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 2: manufactured by Kibun Food Chemifa * 3: Made by Maruzen Pharmaceutical Co., Ltd.
A. Components (1) to (8) are mixed and dissolved.
B. Components (9) to (14) are mixed and dissolved.
C. A is added to B and emulsified to obtain a skin lotion.
The obtained lotion 3 had a clean and light feeling of use, was a lotion that prevented skin inflammation and pigmentation, kept the skin fresh and smoothed the skin.

[Example 12: Latex]
(Ingredient) (%)
(1) Stearic acid 1.0
(2) Cetanol 0.5
(3) Lipophilic glyceryl monostearate 0.5
(4) Liquid paraffin 2.0
(5) Squalane 3.0
(6) Jojoba oil 3.0
(7) Cetyl palmitate 0.2
(8) Preservative appropriate amount (9) Sorbitan monostearate 0.3
(10) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(11) Stearyl glycyrrhetinate * 1 0.2
(12) Triethanolamine 0.5
(13) 1,3-butylene glycol 15.0
(14) Glycerin 3.0
(15) Polyethylene glycol 6000 0.5
(16) Purified water remaining amount (17) 1% solution of carboxyvinyl polymer 8.0
(18) Human squirrel 50 vol% hydrous ethyl alcohol extract * 2 0.5
(19) Neubara extract * 3 0.5
(20) Oat extract * 4 0.5
(21) Fragrance Appropriate amount * 1: Made by Maruzen Pharmaceutical Co., Ltd. * 2: The extract produced in Example 2 dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 3: Maruzen Pharmaceutical Co., Ltd. * 4: manufactured by Maruzen Pharmaceutical Co., Ltd.
A. Components (1) to (11) are dissolved by heating and maintained at 70 ° C.
B. Components (12) to (16) are dissolved by heating and maintained at 70 ° C.
C. B is added to A to emulsify, and component (17) is further added and mixed.
D. C is cooled, and components (18) to (21) are added and mixed to obtain an emulsion.
The obtained emulsion had a smooth and mellow feeling, prevented skin inflammation and pigmentation, added moisturizing feeling and moderate emollient feeling to the skin, and made the skin soft.

[Example 13: Cream]
(Ingredient) (%)
(1) Stearic acid 2.5
(2) Cetanol 2.5
(3) Lipophilic glyceryl monostearate 2.0
(4) Vaseline 2.0
(5) Dipentaerythritol fatty acid ester * 1 2.0
(6) Isotridecyl myristate 5.0
(7) Liquid paraffin 8.0
(8) Squalane 5.0
(9) Beeswax 1.0
(10) Cetyl palmitate 2.0
(11) Sorbitan sesquioleate 0.5
(12) Polyoxyethylene monooleate (20E.O.)
Sorbitan 1.5
(13) Preservative appropriate amount (14) Triethanolamine 1.2
(15) 1,3-butylene glycol 8.0
(16) Glycerin 2.0
(17) Polyethylene glycol 20000 0.5
(18) Purified water Remaining amount (19) Carboxyvinyl polymer 1% aqueous solution 10.0
(20) Arbutin * 2 3.0
(21) Human squirrel 80 vol% hydrous ethyl alcohol extract * 3 1.0
(22) Serine * 4 1.0
(23) Licorice extract * 5 0.5
(24) Yokuinin extract * 6 0.5
(25) Perfume appropriate amount * 1: Cosmol 168AR (Nisshin Oillio Group)
* 2: Wako Pure Chemical Industries, Ltd. * 3: The extract produced in Example 1 dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 4: Ajinomoto Co. * 5: Made by Maruzen Pharmaceutical Co., Ltd. * 6: Made by Maruzen Pharmaceutical Co., Ltd. (Production method)
A. Ingredients (1) to (13) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (14) to (18) are dissolved by heating and maintained at 70 ° C.
C. B is added to A to emulsify, and component (19) is further added and mixed.
D. C is cooled, components (20) to (25) are added and mixed to obtain a cream.
The obtained cream had a smooth and rich feeling of use, prevented skin inflammation and pigmentation, imparted a high emollient feeling to the skin, and made the skin soft.

[Example 14: Cosmetic liquid]
(Ingredient) (%)
(1) Glyceryl tri-2-ethylhexanoate 0.1
(2) Meadow Home Oil 0.05
(3) Jojoba oil 0.05
(4) Retinol palmitate * 1 0.2
(5) Tocopherol acetate * 2 0.1
(6) Preservative appropriate amount (7) perfume appropriate amount (8) polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(9) Polyoxyethylene hydrogenated isostearate castor oil (50 EO) 1.5
(10) Ethyl alcohol 5.0
(11) Glycerin 4.0
(12) Dipropylene glycol 8.0
(13) 1,3-butylene glycol 8.0
(14) Sodium lactate 0.5
(15) Sodium pyrrolidonecarboxylate (50%) solution * 3 0.5
(16) Hydroxyethyl cellulose 0.08
(17) Sodium alginate 0.05
(18) Human squirrel 50 vol% hydrous ethyl alcohol extract * 4 0.2
(19) Carrot extract * 5 0.5
(20) Warmoko extract * 6 0.5
(21) Remaining amount of purified water * 1: Roche * 2: Eisai * 3: Ajinomoto * 4: 50 vol% water containing 1,3 so that the extract produced in Example 2 has a content of 1% -Dissolved in butylene glycol * 5: manufactured by Maruzen Pharmaceutical Co., Ltd. * 6: manufactured by Maruzen Pharmaceutical Co., Ltd. (production method)
A. Components (1) to (9) are mixed and dissolved.
B. Components (10) to (21) are mixed and dissolved.
C. A is added to B and mixed to obtain a serum.
The obtained serum has a mellow and mild feeling of use, prevents skin inflammation and pigmentation, gives the skin a high moisturizing and emollient feeling, and makes the skin fresh and soft. It was.

[Example 15: Pack (Peel-off type)]
(Ingredient) (%)
(1) Polyvinyl alcohol 12.0
(2) Methylcellulose 0.1
(3) Glycerin 3.0
(4) 1,3-butylene glycol 5.0
(5) Purified water remaining amount (6) perfume appropriate amount (7) preservative appropriate amount (8) glyceryl tri-2-ethylhexanoate 0.1
(9) Polyoxyethylene monooleate (20E.O.)
Sorbitan 1.0
(10) Ethyl alcohol 13.0
(11) Hitori Shizuka 80vol% hydrous ethyl alcohol extract * 1 0.5
(12) Sohakuhi extract * 2 0.5
(13) Yokogi extract * 3 0.5
* 1: The extract produced in Example 1 was dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1%. * 2: Maruzen Pharmaceutical Co., Ltd. * 3: Maruzen Pharmaceutical Co., Ltd. (manufacturing method)
A. Components (1) to (5) are dissolved by heating.
B. Components (6) to (10) are mixed and dissolved.
C. After cooling A, B and components (11) to (13) are added and mixed to obtain a pack.
The resulting pack has a moderate refreshment and high tension, prevents skin irritation and pigmentation, gives a moderate moisturizing feel and elasticity to the skin after packing, and softens the skin. It was a pack to do.

[Example 16: Massage cream]
(Ingredient) (%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 2.5
(3) Lipophilic glyceryl monostearate 2.0
(4) Sorbitan sesquioleate 1.0
(5) Cetyl palmitate 1.0
(6) Dipentaerythritol fatty acid ester * 1 4.0
(7) Vaseline 20.0
(8) Liquid paraffin 28.0
(9) Dimethylpolysiloxane (100CS) 0.5
(10) Sodium hydroxide 0.1
(11) Dipropylene glycol 7.0
(12) Carboxyvinyl polymer 0.1
(13) Purified water Residual amount (14) Human volcano 80vol% hydrous ethyl alcohol extract * 2 1.0
(15) Birch extract * 3 0.5
(16) Tea extract * 4 1.0
(17) Perfume appropriate amount * 1: Cosmol 168AR (Nisshin Oillio Group)
* 2: The extract produced in Example 1 was dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1%. * 3: manufactured by Maruzen Pharmaceutical Co., Ltd. * 4: manufactured by Maruzen Pharmaceutical Co., Ltd. (manufacturing method)
A. Ingredients (1) to (9) are dissolved by heating and maintained at 70 ° C.
B. Components (10) to (13) are dissolved by heating and maintained at 70 ° C.
C. A is added to B and emulsified.
D. After cooling C, components (14) to (17) were added and mixed to obtain a massage cream.
The resulting massage cream has a rich and smooth feel, has a high massage effect, prevents skin irritation and pigmentation, moisturizes the skin and gives it a smooth feel. It was a cream.

[Example 17: Liquid foundation]
(Ingredient) (%)
(1) Stearic acid 2.0
(2) Cetanol 0.5
(3) Behenyl alcohol 1.0
(4) Petrolatum 2.5
(5) Liquid paraffin 5.0
(6) Self-emulsifying glyceryl monostearate 1.0
(7) Preservative appropriate amount (8) Titanium oxide 6.0
(9) Color pigment 4.0
(10) Mica 2.0
(11) Talc 4.0
(12) Carboxymethylcellulose 0.2
(13) Bentonite 0.4
(14) Purified water Residual amount (15) Human vol. 50 vol% hydrous ethyl alcohol extract * 1 0.5
(16) Yuzu extract * 2 0.5
(17) Shobu extract * 3 0.5
(18) Fragrance Appropriate amount * 1: The extract produced in Example 2 dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 2: Maruzen Pharmaceutical Co., Ltd. * 3: Maruzen Pharmaceutical Co., Ltd. Made (Manufacturing method)
A. Components (1) to (7) are dissolved by heating.
B. Ingredients (8) to (11) are added to A, mixed uniformly, and kept at 70 ° C.
C. Ingredients (12) to (14) are dissolved by heating and maintained at 70 ° C.
D. B is added to C and emulsified.
E. After cooling D, components (15) to (18) were added and mixed to obtain a liquid foundation.
The obtained liquid foundation was a liquid foundation that had a light and expansive feeling of use, prevented skin inflammation and pigmentation, and had a uniform and beautiful finish.

  The inhibitor of endolysene-1 production and the hexaminidase release inhibitor of the present invention can be used as an active ingredient for external preparations for skin, foodstuffs and the like. In particular, it is useful for external preparations for skin such as cosmetics.

Claims (6)

An endothelin-1 production inhibitor comprising, as an active ingredient, a human squirrel extract using hydrous ethyl alcohol containing 50% by volume or more of ethyl alcohol as an extraction solvent . A hexosaminidase release inhibitor containing, as an active ingredient, a human lizard extract using hydrous ethyl alcohol containing 50% by volume or more of ethyl alcohol as an extraction solvent . Anti-inflammatory agent containing a Hitorishizuka extract as an active ingredient for the water-containing ethanol containing 50 vol% or more of ethyl alcohol and the extraction solvent. Whitening agents containing Hitorishizuka extract hydrous ethyl alcohol containing 50% by volume or more of ethyl alcohol and the extraction solvent as an active ingredient. A method for suppressing the production of endothelin-1 by supplying a human lysizuka extract using hydrous ethyl alcohol containing 50% by volume or more of ethyl alcohol as an extraction solvent to the skin (however, excluding human treatment methods). A method for suppressing the release of hexosaminidase by supplying a human lysizuka extract containing 50% by volume or more of water-containing ethyl alcohol as an extraction solvent to the skin (however, a human treatment method is excluded).