JP6433678B2 - External preparations and internal preparations containing the extract - Google Patents

Description

  The present invention relates to novel antioxidants, ceramide production promoters, cell growth promoters, wrinkle prevention or amelioration agents, testosterone-5α-reductase (hereinafter abbreviated as 5α-reductase) inhibitors, hair restorers, acne and prostate diseases. It relates to a preventive or therapeutic agent.

  The skin is located in the outermost layer of the living body, is an organ in which active oxygen is easily generated due to the influence of ultraviolet rays and the like, and is constantly exposed to the oxygen stress. On the other hand, active oxygen scavenging enzymes exist in the skin cells, and protect the skin cells from injury of active oxygen unless active oxygen exceeding that capacity is generated. However, it is known that the activity of the active oxygen scavenging enzyme in skin cells decreases with age, and when the injury due to active oxygen surpasses its protective reaction, the skin is oxidized and the cell function deteriorates and ages. It is thought that it will do. Also, in organs other than the skin, when exposed to active oxygen exceeding its active oxygen scavenging ability, it is considered that functional deterioration occurs and aging occurs, and various lifestyle-related diseases such as cancer and myocardial infarction develop. Therefore, active oxygen scavengers and antioxidants have been studied for the purpose of protecting against active oxygen injury, and active oxygen scavengers such as SOD and catalase, and active oxygen scavengers and antioxidants such as SOD-like active substances are included. Foods, cosmetics, quasi-drugs and pharmaceuticals have been developed (see Patent Documents 1 and 2).

  Ceramide is a kind of sphingolipid and is a general term for a group of compounds in which sphingosine and a fatty acid are amide-bonded. Ceramide is known to be present at a high concentration in the cell membrane. Ceramide is a component of keratin intercellular lipids, and is secreted extracellularly in the process of keratinization, and plays an important role in the skin barrier function and water retention ability. Furthermore, ceramide is considered to suppress the formation of wrinkles on the skin by having a water retention ability.

  It has been confirmed that eleven types of ceramide are present in human skin, and it is ideal that all types of ceramide are supplemented with a ratio of existing in the stratum corneum. Conventionally, ceramide has been blended into various skin external preparations as a cosmetic that is effective in preventing and improving rough skin and dry skin, but supplements all types of ceramide present in human skin at an appropriate ratio. That was technically difficult. Therefore, it is considered important to promote ceramide production in vivo. Patent Documents 3 and 4 have been reported as ceramide production promoters.

  The proliferation / division ability of epidermal cells decreases with aging, and the epidermal layer itself becomes thin (see Non-Patent Document 2). Epidermal Growth Factor (EGF / epidermal growth factor) and female hormones (estrogens), which are biological factors, act on the proliferation of epidermal cells in the skin, but their secretion decreases with age. Such a decrease in epidermal cell metabolic function due to aging delays the turnover speed of the skin, causing rough skin and aging of the skin. In addition, the horny layer cells that fall off from the stratum corneum surface stay, and the melanin in the epidermis is not excreted smoothly, causing pigmentation and dull skin. It is also known that epidermal wound healing is delayed. In order to prevent or improve the progression of these phenomena, search for components that promote the proliferation of epidermal cells and proposals for many external preparations for skin have been made.

  Conventionally, (1) hormone imbalance theory, (2) genetic theory, (3) blood circulation failure theory, (4) nutrition theory, etc. have been proposed as causes of male pattern alopecia. It has long been suggested that the male hormone testosterone plays an important role. That is, testosterone biosynthesized by testicles is converted to dihydrotestosterone by 5α-reductase present in hair follicles, sebaceous glands and the like in the head. This dihydrotestosterone significantly reduces the activity of adenylate cyclase resulting in a decrease in intracellular cyclic AMP levels. As a result, it is considered that male pattern baldness progresses by inducing a decrease in energy production around hair and hair and suppression of protein synthesis.

  Further, dihydrotestosterone produced from testosterone by 5α-reductase is considered to be involved in acne generation and exacerbation (see Non-Patent Document 1). Furthermore, it is known that when the production of dihydrotestosterone increases, prostate diseases such as prostatic hypertrophy and prostate cancer develop, and it is possible to suppress or inhibit the production of dihydrotestosterone by a drug having a 5α-reductase inhibitory action. If possible, it is believed that prostate disease can be prevented and treated.

  Known literatures of Uguisukagra have been known to inhibit S. aureus enterotoxin production and prevent atopic dermatitis exacerbation (Patent Document 5).

JP-A-9-118630 JP-A-9-208484 JP-A-8-217658 JP 2001-220345 A JP 2001-226280 A J. et al. Steroid Biochemistry, 11, 609 (1979)

  An object of the present invention is to provide a novel skin external preparation or internal preparation excellent in an antioxidant effect, a ceramide production promoting effect, a cell proliferation effect, a wrinkle prevention or improvement effect, and a 5α-reductase inhibition effect.

  As a result of intensive studies to solve this problem, the present inventors have obtained an extract of warbler mothgrass as an antioxidant effect, a ceramide production promoting effect, a cell proliferation effect, a wrinkle prevention or improvement effect, and a 5α-reductase. It discovered that the inhibitory effect was excellent and came to complete this invention.

  The warbler grass or extract thereof of the present invention has an excellent antioxidant effect, ceramide production promoting effect, cell proliferation effect, wrinkle prevention or improvement effect, 5α-reductase inhibitory effect, pharmaceuticals, quasi drugs, It can contribute in the field of cosmetics and food.

  The present invention will be described in detail below.

  The extract of the squirrel used in the present invention is extracted from a part of the plant body such as flowers, berries, seeds, stems, leaves, roots or the whole plant of the squirrel family honeysuckle (scientific name: Lonicera gracilipes). Is. The extraction method is not particularly limited, and for example, it may be a heat extraction or a room temperature extraction.

  Examples of the extraction solvent include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol, Glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether, etc.) ). Preferred are polar solvents such as water, lower alcohols and liquid polyhydric alcohols, and particularly preferred are water, ethanol, 1,3-butylene glycol and propylene glycol. These solvents may be used alone or in combination of two or more.

  The extract may be used as it is, or may be used after concentration, dilution and filtration treatment, decolorization with activated carbon, deodorization treatment, or the like, if necessary. Further, the extracted solution may be subjected to a treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product.

  The above-mentioned extract may be used as it is for the external preparation or internal preparation of the present invention, and is a component used for cosmetics, quasi drugs, pharmaceuticals, foods, etc., as long as these effects are not impaired. Fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments In addition, components such as an antioxidant, a whitening agent, a chelating agent, an excipient, a film agent, a sweetener, and a sour agent can be blended. Examples of other drugs that are commonly used as hair restorers include vasodilators such as assembly extract and acetylcholine derivatives, swelltinogen, vitamin E nicotinic acid ester, red pepper tincture, and ginseng. One or more of these can be used. In addition, other drugs commonly used as acne treatments include, for example, steroids such as prednisolone valerate acetate and hydrocortisone acetate, vitamins such as ascorbic acid and pyridoxine hydrochloride, and wound healing agents such as allantoin. These can be used alone or in combination of two or more.

  The present invention can be used for pharmaceuticals, quasi drugs, cosmetics, and foods. Examples of the dosage form include lotions, creams, massage creams, emulsions, gels, aerosols, packs, detergents, hairs. Tonic, hair lotion, hair cream, hair conditioner, hair gel, hair mist, hair foam, shampoo, rinse, bath preparation, foundation, dusting, lipstick, ointment, poultice, paste, plaster, essence, powder, pill, tablet , Injections, suppositories, emulsions, capsules, granules, liquids (including tinctures, fluid extracts, spirits, suspensions, limonades, etc.).

  In the case of external use, the amount of the extract used in the present invention is preferably 0.0001% by weight or more, more preferably 0.001 to 10% by weight, in terms of solid matter, based on the total amount. Furthermore, 0.01 to 5% by weight is most preferable. If it is less than 0.0001% by weight, a sufficient effect is hardly expected. When the blending amount exceeds 10% by weight, the effect is hardly recognized and it is uneconomical. On the other hand, for internal use, the dose varies depending on age, weight, symptoms, therapeutic effects, administration method, treatment time, etc., but the daily dose per adult is usually preferably 5 mg or more, and 10 mg to 5 g. Is more preferable. Furthermore, 100 mg to 1 g is most preferable.

  Next, in order to describe the present invention in detail, examples of production, experimental examples, and formulation examples of the extract of warbler mothgrass used in the present invention will be given as examples, but the present invention is not limited thereto. In the production examples, “%” means “% by weight”, and “parts” in the examples means “parts by weight”.

Production example 1 Hot water extract 1
Purified water (200 mL) was added to 10 g of dried dried liquorice, extracted at 95-100 ° C. for 2 hours, filtered, and the filtrate was concentrated and freeze-dried to obtain 1 hot-water extract 1 .4 g was obtained.

Production Example 2 50% Ethanol Extract of Uguisukagra 200ml of 50% ethanol was added to 10g of dried Ugizukagra whole plant, extracted for 7 days at room temperature, filtered, and the filtrate was concentrated to dryness. 1.2 g of a 50% ethanol extract was obtained.

Production Example 3 Ethanol extract of Uguisukagra 200 mL of ethanol was added to 10 g of dried Ugizukagra whole plant, extracted at room temperature for 7 days, filtered, the filtrate was concentrated to dryness, and the extract of Uguisukagra was extracted. 0.3g was obtained.

Production Example 4 50% 1,3-Butyleneglycol Extract of Uguiscagra Add 400 g of 1,3-butyleneglycol to 10 g of dried Uguiskagra whole plant, extract at room temperature for 7 days, filter, 380 g of 1,3-butylene glycol extract was obtained.

Production Example 5 Hot water extract 2
Purified water (200 mL) was added to 10 g of dried oyster grass leaves and extracted at 95-100 ° C. for 2 hours, followed by filtration. The filtrate was concentrated and lyophilized to obtain 2. 4 g was obtained.

Manufacture example 6
200 g of purified water was added to 10 g of dried squirrel stalk and extracted at 95-100 ° C. for 2 hours, followed by filtration. The filtrate was concentrated and freeze-dried to obtain 0. 9 g was obtained.

Formulation Example 1 Lotion Prescription Formulation Amount (parts)
1. Warbler's hot water extract 1 (Production Example 1) 1.0
2.1,3-Butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7). Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Perfume proper amount11. [Manufacturing method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved in purified water, and both are mixed and filtered to obtain a product.

Formulation Example 2 Cream Formulation Amount (parts)
1. 50% ethanol extract of mussel (Production Example 2) 0.5
2. Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.1
11. Methyl paraoxybenzoate 0.2
12 Ethyl paraoxybenzoate 0.05
13.1,3-Butylene glycol 8.5
14 [Manufacturing method] Components 2 to 9 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 11 to 14 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring.

Formulation Example 3 Emulsion Formulation Blending amount (parts)
1. Hot water extract of warbler sharkgrass 2 (Production Example 5) 0.001
2. Squalane 5.0
3. Olive oil 5.0
4). Jojoba oil 5.0
5. Cetanol 1.5
6). Glycerol monostearate 2.0
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Polyoxyethylene sorbitan monooleate (20E.O.) 2.0
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12 Methyl paraoxybenzoate 0.2
13. [Manufacturing method] Components 2 to 8 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 10-13 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 9 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 4 Gel formulation Formulation Amount (parts)
1. Hot water extract 3 (Production Example 6) 1.0
2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
5. Perfume appropriate amount 6.1,3-butylene glycol 5.0
7). Glycerin 5.0
8). Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. [Production method] Ingredients 2 to 5 and ingredients 1 and 6 to 11 are uniformly dissolved in purified water, and the two are mixed to obtain a product.

Formulation Example 5 Pack Formulation Amount (parts)
1. Hot water extract 1 (Production Example 1) 0.1
2. 50% ethanol extract of mussel (Production Example 2) 0.1
3. Polyvinyl alcohol 12.0
4). Ethanol 5.0
5.1,3-butylene glycol 8.0
6). Methyl paraoxybenzoate 0.2
7). Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
8). Citric acid 0.1
9. Sodium citrate 0.3
10. Perfume proper amount11. [Production Method] Components 1 to 11 are uniformly dissolved in purified water to make a total amount of 100 to obtain a product.

Formulation Example 6 Foundation Formulation Amount (parts)
1. Ethanol extract of warbler grass (Production Example 3) 1.0
2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20E.O.) 1.0
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7). Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Sodium carboxymethylcellulose 0.1
10. Bentonite 0.5
11. Propylene glycol 4.0
12 Triethanolamine 1.1
13. Methyl paraoxybenzoate 0.2
14 Titanium dioxide 8.0
15. Talc 4.0
16. Bengala 1.0
17. Yellow iron oxide 2.0
18. Perfume proper amount19. [Manufacturing method] Components 2 to 8 are heated and dissolved in purified water to a total amount of 100, and kept at 80 ° C to obtain an oil phase. Swell component 9 well in component 19, then add components 1 and 10-13 and mix uniformly. To this, components 14 to 17 pulverized and mixed with a pulverizer are added, and the mixture is stirred with a homomixer and kept at 75 ° C. to obtain an aqueous phase. The water phase is added to this oil phase with stirring, cooled, and component 18 is added at 45 ° C., and cooled to 30 ° C. with stirring to give a product.

Formulation Example 7 Bath preparation Formulation Blending (parts)
1. Hot water extract 1 (Production Example 1) 5.0
2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Appropriate amount 4. Perfume appropriate amount 5. [Manufacturing method] Ingredients 1 to 5 are mixed uniformly with sodium sulfate to make a product.

Formulation Example 8 Ointment Formulation Amount (parts)
1. Hot water extract 1 of Uguisukagra (Production Example 1) 0.01
2. 50% 1,3-butylene glycol extract of Warbler squirrel (Production Example 4) 0.5
3. Polyoxyethylene cetyl ether (30E.O.) 2.0
4). Glycerol monostearate 10.0
5. Liquid paraffin 5.0
6). Cetanol 6.0
7). Methyl paraoxybenzoate 0.1
8). Propylene glycol 10.0
9. [Production Method] Components 3 to 6 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C. to obtain an oil phase. Ingredients 1, 2, and 7-9 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled to 30 ° C. with stirring to obtain a product.

Formulation Example 9 Hair Lotion Formulation Amount (parts)
1. Hot water extract 1 (Production Example 1) 0.2
2. Stearic acid 5.0
3. Cetyl alcohol 5.0
4). Liquid paraffin 2.0
5. Glycerin monostearate 1.3
6). Sorbitan monostearate 1.5
7). Polyoxyethylene sorbitan monooleate (10E.O.) 0.8
8). Glycerin 6.0
9. Preservative appropriate amount10. [Production method] Components 2 to 7 were heated and dissolved and mixed with purified water to 100. The oil phase was maintained at 70 ° C. Ingredients 1 and 8 to 10 were dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. An aqueous phase was added to the oil phase, and the mixture was cooled while stirring to obtain a product.

Formulation Example 10 Hair Tonic Formulation Amount (parts)
1. Uguisukagra ethanol extract (Production Example 3) 2.0
2.95% ethanol 60.0
3. Glycerin 2.0
4). [Manufacturing method] Component 1 was dissolved in 2 with purified water to 100, and components 3 and 4 were added and mixed with sufficient stirring to obtain a product.

Formulation Example 11 Shampoo Formulation Amount (parts)
1. 50% ethanol extract of mussel (Production Example 2) 0.1
2. Alkyl sulfate triethanolamine 18.0
3. Lauric acid diethanolamide 3.0
4). Methylcellulose 0.5
5. Perfume appropriate amount 6. [Manufacturing method] in which component 4 is uniformly dissolved in component 6 with purified water 100, components 1 and 2 are added, heated and dissolved at 70 to 75 ° C, component 3 is added, and cooling is in progress. Ingredient 5 was added and cooled to 30 ° C. to obtain a product.

Formulation Example 12 Rinse Formulation Amount (parts)
1. 50% 1,3-butylene glycol extract of Warbler squirrel (Production Example 4) 0.1
2. Jojoba oil 0.01
3. Behenyl alcohol 3.0
4.1,3-Butylene glycol 5.0
5. Distearyldimethylammonium chloride (75%) 8.0
6). Citric acid 0.05
7). Perfume appropriate amount 8. [Manufacturing method] Components 1 to 8 were dissolved at 60 ° C., and the total amount was 100 with purified water, stirred and cooled to 30 ° C. to obtain a product.

  Next, experimental examples will be given to explain the effects of the present invention in detail.

Experimental Example 1 Free radical scavenging removal test The free radical scavenging removal action was evaluated. Ascorbic acid was used as a positive control. As a free radical model, α, α-diphenyl-β-picrylhydrazyl (hereinafter referred to as DPPH), which is a stable free radical, is used and reacted with a sample at a certain rate for a certain period of time. Was measured from the decrease in absorbance at a wavelength of 517 nm.

Method for measuring free radical scavenging and removing action Each sample was added to 2 mL of 0.1 M acetate buffer (pH 5.5) added to a final concentration of 0.1 mg / mL, and 2 mL of absolute ethanol and 1 mL of 0.5 mM DPPH absolute ethanol solution. Was added to prepare a reaction solution. In the case of an oil-soluble sample, the sample was added to 2 mL of absolute ethanol to prepare a reaction solution. Then, it was made to react at 37 degreeC for 30 minute (s), and the light absorbency (A) of wavelength 517nm was measured by using water as a control. Moreover, the light absorbency (B) was measured using the purified water instead of the sample as a blank. The free radical scavenging removal rate was calculated from the following equation.
Free radical scavenging removal rate (%) = (1−A / B) × 100

  The test results are shown in Table 1. It was confirmed that the extract of Uguisukagra has a stable and excellent free radical scavenging and removing action. In addition, when ascorbic acid was used, it deactivated by heating at 100 ° C. for 1 hour, but the extract of Uguisukagra of the present invention did not change in activity.

Experimental Example 2 Ceramide Production Promotion Test 1 × 10 ⁵ HaCaT cells, a human epidermal keratinocyte-derived cell line, were seeded in a 60 mm dish and cultured for 4 days. Thereafter, the sample was added to a final concentration of 1 μg / mL, and further cultured for 24 hours. Next, the cells were washed three times with PBS (−), then detached with a rubber policeman, collected, and lyophilized. Lipids were extracted from cells with 1 mL of chloroform: methanol (2: 1), and the amount of ceramide in the cells was determined using a fluorescence method such as Kisic et al. (Kisic A. and Rapport MM, Journal of Lipid Research, 15, 179-180. (1974)). That is, lipids were hydrolyzed with 0.15 mL of 3N hydrochloric acid at 100 ° C. for 2 hours, dried in a desiccator, removed with hydrochloric acid, and then added with 2 mL of ethyl acetate and 1.25 mL of 0.1N acetate buffer (pH 3.7). Stir well. Next, 0.25 mL of a fluorescamine solution (fluorescamine 7 mg / 25 mL acetone) was added, stirred well, then centrifuged, and the fluorescence intensity of the ethyl acetate layer was measured at Ex 410 nm and Em 490 nm. The ceramide production promotion rate was calculated by the following formula.

Ceramide production promotion rate (%) = (ceramide production amount with sample added / control ceramide production amount) × 100

  The results of these experiments are shown in Table 2. It was confirmed that the extract of Uguisukagra has an excellent ceramide production promoting action.

Experimental Example 3 Cell Growth Promotion Test DMEM culture containing 0.1% FBS in which 5 × 10 ³ keratinocyte-derived HaCaT cells were seeded per well in a 96-well plate and the sample was added to a final concentration of 0.1 μg / mL. The solution was used and cultured at 37 ° C. under 5% CO _{2 for} 4 days. The number of cells was measured by a staining method. Specifically, after completion of the culture, the culture solution was removed, and the cells were fixed with methanol for 10 minutes. Subsequently, 0.1% methylene blue was added and the cells were stained for 1 hour. After drying, 100 μL of 0.1N HCl was added to each well and stirred well, and the absorbance at 650 nm was measured using a microplate reader. The n number of one specimen was 6.

  The results of these experiments are shown in Table 3. As a result, the extract of Uguisukagra showed an excellent cell growth promoting action on keratinocytes.

Experimental Example 4 5α-Reductase Activity Inhibition Test Using rat liver microsome-derived 5α-reductase, measurement was performed under the following reaction conditions.
After dissolving testosterone (final concentration 0.49 mM) in DMSO, NADPH (final concentration 0.97 mM) dissolved in 0.1 M Tris-HCl buffer (pH 7.2) was added, and then the sample and 5α- Reductase was added in order and reacted at 37 ° C. for 30 minutes. After the reaction, an equal amount of dichloromethane was added to stop the reaction, and then the dichloromethane layer was extracted. Then, the dichloromethane layer was distilled off under reduced pressure, and after silylation using BSTFA, the reaction amount was measured by a conventional method using a gas chromatography mass spectrometer. The inhibition rate is determined by using purified water instead of the sample as a control, assuming that the control reaction rate is 100% (inhibition rate 0%), and calculating the amount of reaction with the sample added to determine the inhibition rate. It was. The formula is as follows.

Inhibition rate (%) = (1− (b ′ / a ′) / (b / a)) × 100
a: Peak area of testosterone (control)
b: Peak area of dihydrotestosterone (control)
a ′: Testosterone peak area (sample addition)
b ′: Peak area of dihydrotestosterone (sample addition)

  These results are summarized in Table 4. As a result, the extract of Uguisukagra showed an excellent inhibitory activity on 5α-reductase activity.

  From the above, the extract of Warbler mothgras showed excellent antioxidant effect, ceramide production promotion effect, cell proliferation effect, wrinkle prevention or improvement effect, and 5α-reductase activity inhibitory effect, and was also excellent in stability. Skin external preparations or internal preparations containing these are particularly effective.

Claims (3)

  Antioxidant characterized by containing an extract of Warbler cagra. The ceramide production promoter characterized by including the extract of the stem and / or leaf of a warbler. A keratinocyte growth promoter characterized by containing an extract of warbler (excluding steam distillate of fruits) .