KR101835739B1 - Composition comprising extracts or fractions of Artemisia capillaris as an effective ingredient - Google Patents
Composition comprising extracts or fractions of Artemisia capillaris as an effective ingredient Download PDFInfo
- Publication number
- KR101835739B1 KR101835739B1 KR1020150086839A KR20150086839A KR101835739B1 KR 101835739 B1 KR101835739 B1 KR 101835739B1 KR 1020150086839 A KR1020150086839 A KR 1020150086839A KR 20150086839 A KR20150086839 A KR 20150086839A KR 101835739 B1 KR101835739 B1 KR 101835739B1
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- KR
- South Korea
- Prior art keywords
- ethyl acetate
- extract
- fraction
- concentration
- solvent
- Prior art date
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- 239000000284 extract Substances 0.000 title claims abstract description 106
- 239000000203 mixture Substances 0.000 title claims abstract description 84
- 241000092668 Artemisia capillaris Species 0.000 title claims abstract description 20
- 235000008658 Artemisia capillaris Nutrition 0.000 title claims abstract description 20
- 239000004615 ingredient Substances 0.000 title description 3
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- 239000004480 active ingredient Substances 0.000 claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 claims abstract description 17
- 239000012046 mixed solvent Substances 0.000 claims abstract description 14
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 138
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 87
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 87
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- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
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Images
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
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- Alternative & Traditional Medicine (AREA)
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Abstract
The present invention relates to a composition having anti-inflammatory, antioxidant, skin whitening activity, and anti-inflammatory, antioxidative, skin whitening activity enhancing activity, or a method for producing the fractions thereof, which comprises an extract of Artemisia princeps or a fraction thereof as an active ingredient.
Specifically, extracts of Artemisia capillaris or fractions thereof, which are extracted with water, alcohol or a mixed solvent thereof, are excellent in anti-inflammation, antioxidant and skin whitening activity, and particularly in melanoma cells, melanocytes, Production inhibitory effect, and showed very high activity even in a small amount.
Therefore, the composition containing the extract of Artemisia princeps of the present invention or a fraction thereof as an active ingredient can be usefully applied to cosmetic preparations, soaps, medicines or food compositions.
Description
The present invention relates to a composition having anti-inflammatory, antioxidant, skin whitening activity, and anti-inflammatory, antioxidative, skin whitening activity enhancing activity, or a method for producing the fraction thereof, which comprises Artemisia capillaris extract or a fraction thereof as an active ingredient will be.
In human skin, various physical and chemical changes occur during the aging process. The cause is largely classified into intrinsic aging and photo-aging, and research has been conducted actively. Specifically, free radicals may be activated by ultraviolet rays, stress, disease states, environmental factors, wounds, and aging. If such conditions are deepened, the antioxidant defense network existing in the living body may be destroyed, Thereby promoting adult diseases and aging.
Therefore, it is necessary to protect the cell membrane by destroying the free radicals mediated by free radicals, ultraviolet rays, and inflammation that occur during the metabolism of the body and to proliferate cells by regenerating already damaged cells by active metabolism The skin can be maintained.
On the other hand, melanin is oxidized by tyrosinase to tyrosine (DOPA, 3,4-dihydro xyphenylalanine), converted to dopaquinone by redox oxidation, and then converted to non-enzymatic oxidation Reaction. Melanin protects the skin organs below the dermis by blocking ultraviolet rays, and at the same time, it plays a useful role in protecting the damage of proteins and genes in skin caused by free radicals generated in the skin of the skin. However, when melanin is produced more than necessary, It causes aging and causes hyperpigmentation such as spots or freckles. Melanin has the ability to remove reactive oxygen species, but sometimes melanin itself generates free radicals. It also reduces or oxidizes other substances by catechol or quinone in the melanin structure, and melanin itself has the property of free radicals do. Therefore, inhibition of melanin production may result in a skin whitening effect.
(P-methoxyphenol), hydroquinone, kojic acid, albutin, vitamin C (ascorbic acid), glutathione (glutathione) and the like, which have a skin whitening effect by inhibiting melanin production. glutathione and cystein and plant extracts such as extracts of cucumber herb extract, licorice extract, peony extract, cinnamon extract, gossam extract, Puerariae Radix extract, Angelica gigantosa extract, Problems such as insufficient whitening effect, safety to skin, stability in formulations when added to cosmetics, and the like are still problems to be solved.
Artemisia is a perennial herbaceous plant of Compositae which is distributed in Korea and Asia and Europe. It is known that there are about 400 species. About 300 species are native to Korea, 10-0401472 (Functional beverage containing Artemisia sp. Extract and method for producing the same) describes Artemisia sp. Extract for use in blood vessel relaxation, stroke prevention, or anticancer beverage.
A method for obtaining fractions using solvent polarity for natural products such as mugwort is to sequentially treat hexane, chloroform, dichloromethane, ethyl acetate, and butanol to fractionate the fractions according to the polarity. However, this method has an advantage of being capable of subdividing the substance according to the polarity, but in the experiment for separating the active ingredient, the active ingredient is dispersed.
Accordingly, the inventors of the present invention have devised a method of preventing the dispersion of the active ingredient and obtaining a larger amount of active fraction as compared with the known solvent fractionation method, And to develop a method for producing the extract of Artemisia princeps or its fractions which can best exhibit whitening activity.
It is an object of the present invention to provide a cosmetic composition, a soap composition, a pharmaceutical composition and a cosmetic composition which are effective for anti-inflammation, antioxidant or skin whitening while harmless to the human body by preparing the extract of Artemisia capillaris and its fractions which can best exhibit anti- To provide a food composition.
In addition, the object of the present invention is to provide a method for producing an Artemisia sp. Extract comprising extracting dried matter of Artemisia princeps with water or ethanol / methanol, or extracting and fractionating Artemisia sp. .
In order to achieve the above object, the present invention provides a composition having anti-inflammatory, antioxidant or skin whitening activity, comprising an extract of Artemisia princeps or a fraction thereof as an active ingredient.
The extract of Artemisia capillaris is characterized by being extracted with water, C 1 -C 2 alcohol or a mixed solvent thereof.
Wherein the extract is obtained by extracting an extract of Artemisia japonica with a solvent selected from water, methanol, ethanol or a mixed solvent thereof, and then extracting it again with a mixed solvent of water and ethyl acetate as a solvent.
The above-mentioned fraction of Artemisia princeps is obtained by extracting the extract of Artemisia capillaris with ethyl acetate and further extracting the ethyl acetate fraction with a mixed solvent of methanol and hexane as a solvent.
Wherein the methanol extract is extracted with ethyl acetate and the ethyl acetate fraction is further extracted with a solvent mixture of methanol and hexane to obtain a methanol fraction and the methanol fraction is separated by using a mixed solution of ethyl acetate and hexane .
The mugwort extract or its fractions are characterized by inhibiting NO production, eliminating free radicals, and inhibiting tyrosinase activity and melanin production.
The composition is characterized by being a cosmetic composition, a soap composition, a pharmaceutical composition or a food composition.
The cosmetic composition is characterized by being made of a skin, lotion, cream, essence, gel, pack, cleansing foam, cleansing lotion, cleansing cream, body cream, body lotion, body cleanser, milky lotion, powder or eye shadow formulation.
The composition is characterized by being a pharmaceutical composition for preventing or treating acne, atopy, psoriasis, dermatitis, skin aging, wrinkles or skin hyperpigmentation diseases.
The skin hypercholesterolemic disease is characterized by pigmentation by spots, freckles, blotch, nevus, melanoma, drug, or inflammation.
The present invention also provides a method for preparing a dried eggplant wormy; And
And extracting the dried material with water, a C 1 to C 2 alcohol or a mixed solvent thereof.
In addition, the present invention provides a method of making an Artemisia sp. Fraction comprising the steps of:
(1) preparing a dried mugwort artificially;
(2) extracting the dried material with water, a C 1 to C 2 alcohol, or a mixed solvent thereof; And
(3) Extracting the extract obtained in the step (2) with a mixed solution of ethyl acetate and water as a solvent.
The step of extracting the extract obtained in the step (3) with a mixed solvent of methanol and hexane as a solvent, or a step of extracting a mixed solution of methanol and hexane with a solvent, and then adding the obtained extract to a mixed solution of ethyl acetate and hexane And separating the reaction mixture into a solvent.
According to the present invention, it is possible to provide a cosmetic composition having excellent antiinflammatory, antioxidant and skin whitening effects by providing an extract of Artemisia syrup extract having anti-inflammatory, antioxidant and skin whitening activity and anti-inflammation, antioxidant and skin whitening activity, , A soap composition, a pharmaceutical composition and a food composition.
In addition, the composition containing the extract of Artemisia japonica extract according to the present invention as an active ingredient has an effect of preventing or improving acne, atopy, psoriasis, dermatitis, skin aging, wrinkles or skin hyperpigmentation diseases while being safe for skin.
Also, according to the present invention, it is possible to develop a cosmetic composition or a soap composition having an excellent skin whitening effect by providing a composition containing an ethylacetate fraction or a methanol fraction of an artemisinus having high skin whitening activity and a method for producing the same.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view showing a process for producing the extract of the present invention or its fractions. FIG.
FIG. 2 is a graph showing the NO inhibiting activity of the extract of Artemisia princeps of the present invention.
FIG. 3 is a graph showing the DPPH radical scavenging activity of the extract of Artemisia princeps of the present invention.
FIG. 4 is a graph illustrating cytotoxicity of the extract of Artemisia princeps of the present invention.
FIG. 5 is a photograph showing the activity of suppressing intracellular melanin formation of the extract of Artemisia princeps of the present invention.
FIG. 6 is a graph showing the results of measuring intracellular melanin formation inhibitory activity of the extract of Artemisia princeps of the present invention.
FIG. 7 is a graph showing the results of measuring intracellular tyrosinase inhibitory activity of the extract of Artemisia princeps of the present invention.
FIG. 8 is a photograph and a graph showing the results of measurement of melanin production inhibitory activity of the extract of Artemisia japonica extract (a), ethyl acetate fraction (b) and water fraction (c) of the present invention.
FIG. 9 is a photograph and a graph showing the results of measuring the melanin production inhibitory activity of the methanol fraction and the hexane fraction of the present invention.
FIG. 10 is a photograph showing the results of confirming distribution of an active ingredient using the TLC of the individual extract of Artemisia princeps or extract of the present invention.
(A) Staining solution: Vanillin / H2SO4;
(B)
(C)
E: ethyl acetate fraction;
H: water fractions;
M: methanol fraction;
He: hexane fraction; And
Phosphorus: Artemisia extract (ethanol extract).
FIG. 11 is a photograph of melanin production inhibitory activity of each of the detailed fraction fractions (Fr. 1 to Fr. 7) of the present invention.
Hereinafter, the present invention will be described in detail.
The present invention provides a composition having an anti-inflammatory, antioxidant or skin whitening activity containing Artemisia capillaris extract or a fraction thereof as an active ingredient, and a composition for treating the same.
Artemisia capillaris (AC), a member of the genus Chrysanthemum mugwort, is known as an artemisia capillaris (AC), and its young stem and leaves are known to be indigenous to each other in Korea, and there are known dandruff, asthma suppression, Scoparone, Chlorogenic acid, Capillin, etc. are known as the components (Lee, Seong-hyun, pp. 1016-1017, 1998). A perennial herb belonging to Asteraceae Mugwort is several species as follows. Even if they belong to the same genus, they exhibit different effects due to differences in their characteristics, contained components and active substances.
The composition according to the present invention may be contained in any amount within a range that the extract of Artemisia princeps or its fraction is not toxic to the human body, and may be contained in an amount of 0.001 to 99.99% by weight based on the total weight of the composition.
The extract or its fractions inhibit NO production, eliminate active oxygen species, inhibit tyrosinase activity and melanin production, and are mediated by free radicals, ultraviolet irradiation, and inflammation during body metabolism It protects cell membranes by destroying the free radicals that are already damaged, and it has the effect of regenerating already damaged cells by active metabolism and proliferating cells.
Accordingly, the anti-inflammatory, antioxidant and skin whitening compositions containing the extract of Artemisia princeps or extract thereof according to the present invention as an active ingredient are effective for eliminating skin whitening effect, whitening effect and prevention and treatment of inflammatory reaction and eliminating free radicals, To prevent aging and maintain a clear and healthy skin.
In a specific embodiment of the composition according to the present invention, the composition may be used as a cosmetic composition. Forms such as emulsions, lotions, creams (water-in-oil type, water-in-water type, multiphase), solutions, suspensions (anhydrous and aqueous), anhydrous compounds (oil and glycol), gels, masks, packs or powders Oils, surfactants, fatty acids, silicone oils, wetting agents, moisturizers, viscosifying agents, emulsifiers, stabilizers, sunscreen agents, and the like, which can be suitably selected and used by those skilled in the art in cosmetic formulations , A coloring agent, a perfume, and the like.
In another specific embodiment of the composition according to the present invention, the composition may be used as a soap composition. Emulsifying agent, water softening agent, etc. as an additive to a soap base such as palm oil, palm oil, soybean oil, pharmacopoeial, olive oil and palm kernel oil, or animal fats such as tallow, lard, have. As the above-mentioned skin moisturizing agent, glycerin, erythritol, polyethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexyl glycol, isopropyl myristate, silicone derivatives, aloe vera, sorbitol, Wax fatty alcohols, hydrocarbons, natural plant extracts and the like can be used. As the water softening agent, tetrasodium edetate and the like can be used. The additive may further include an antimicrobial agent, a dispersant, a foam inhibitor, a solvent, a scouring inhibitor, a corrosion inhibitor, a perfume, a dye, a sequestering agent, an antioxidant, an antiseptic and the like.
In another specific embodiment of the composition according to the present invention, the composition can be used as a pharmaceutical composition. Specifically, it is a skin irritant caused by acne, atopy, psoriasis, dermatitis and the like caused by inflammation reaction, skin aging caused by increase of active oxygen, wrinkles, and stain, freckles, blotch, It can be used as a pharmaceutical composition having a preventive or therapeutic effect on a skin pigmentation disease such as a pigment, a pigment, a drug-induced pigmentation, and an inflammation-induced pigmentation. The pharmaceutical composition can be administered at various times during clinical administration, including oral, transdermal, subcutaneous, intravenous, or muscular, and can be applied as an external preparation for skin. In addition, formulations can be prepared in various formulations. In the case of formulation, formulations can be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants that are usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose and gelatin, . Examples of liquid preparations for oral administration include suspensions, solutions, emulsions and syrups. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances and preservatives . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Witepsol, macrogol, tween 61, cacao paper, laurin, glycerol and gelatin may be used as a base for suppositories.
The composition of the present invention may be administered orally or parenterally in accordance with the intended method, and may be administered orally, parenterally or intraperitoneally, rectally, subcutaneously, intravenously, intramuscularly, . The dosage varies depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and disease severity.
The dosage of the composition of the present invention varies depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of disease, , Preferably 0.001 to 10 mg / kg, and may be administered 1 to 6 times a day.
The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
The health food of the present invention can be used as it is, or can be used in combination with other food or food ingredients, and can be suitably used according to a conventional method.
There is no particular limitation on the kind of the health food. Examples of the foods to which the mugwort extract or the fractions thereof can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen and other noodles, gums, ice cream, Tea, a drink, an alcoholic beverage, and a vitamin complex, all of which include health foods in a conventional sense.
The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 g of the composition of the present invention.
In addition to the above, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, , A carbonating agent used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
The present invention provides a method for producing Artemisia sp. Extract comprising extracting and fractionating Artemisia sp. Extract with an organic solvent.
The extract of Artemisia princeps or extract thereof according to the present invention is preferably produced by a method comprising the following steps, but is not limited thereto.
1) extracting Artemisia capillaris extract with an extraction solvent;
2) filtering the extract of step 1);
3) concentrating the filtered extract of step 2) under reduced pressure and then drying to prepare an extract of Artemisia princeps; And
4) Extraction of Artemisia sp. Extract of step 3) with an organic solvent to produce Artemisia sp. Fractions.
In this method, Artemisia Capillaris of step 1) can be used without limitation, such as cultivated or commercially available. It is most preferable that all organs such as leaves, flowers, roots, stems, and seeds are available, but it is not limited thereto.
In the above method, the extraction solvent of step 1) is preferably water, an alcohol or a mixture thereof. As the alcohol, C 1 to C 2 lower alcohol is preferably used, and as the lower alcohol, ethanol or methanol is preferably used. As the extraction method, it is preferable to use shaking extraction, Soxhlet extraction or reflux extraction, but it is not limited thereto. The extraction solvent is preferably added 1 to 5 times, more preferably 1 to 2 times, more preferably 1.5 times, more preferably 1 to 5 times. The extraction temperature is preferably 20 占 폚 to 100 占 폚, more preferably 20 占 폚 to 40 占 폚, and most preferably room temperature, but is not limited thereto. Further, the extraction time is preferably 10 to 48 hours, more preferably 12 to 36 hours, but is not limited thereto. The number of times of extraction is preferably 1 to 5 times, more preferably 1 to 2 times, more preferably 1 time, but is not limited thereto.
In the above method, it is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator in order to reduce the pressure in step 3), but the concentration is not limited thereto, and the concentration may be about 2 to 10 Brix as measured by a sugar content meter More preferably 3 to 6 bricks, but it is not limited thereto. The drying is preferably performed under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, but not always limited thereto.
In the above method, the organic solvent in step 4) may be ethyl acetate, methanol, hexane, or a mixed solution thereof, preferably a mixed solution of water and ethyl acetate, a mixed solution of methanol and hexane, or a mixed solution of ethyl acetate and hexane But is not limited thereto.
The method for producing the fragrance fraction of step 4) may include extracting the extract of Artemisia princeps, using a mixed solution of water and ethyl acetate as a solvent, thereby obtaining the ethyl acetate fraction of the present invention.
At this time, the concentration of ethyl acetate in the mixed solution of water and ethyl acetate is preferably 40 to 70% by volume, more preferably 50 to 60%, most preferably 50%, but is not limited thereto.
The method for producing the fragrance fraction of step (4) may further include extracting the ethyl acetate fraction of the present invention using a mixed solvent of methanol and hexane as a solvent, thereby obtaining the methanol fraction of the present invention .
At this time, the concentration of methanol in the mixed solution of methanol and hexane is preferably 70 to 95% by volume, more preferably 80 to 90%, most preferably 90% It is possible.
The method for preparing the fragrant fraction of step 4) may include separating the methanol fraction of the present invention using a mixed solvent of ethyl acetate and hexane as a solvent, Fr.7) can be obtained.
At this time, the concentration of ethyl acetate in the mixed solution of ethyl acetate and hexane is preferably 10 to 70%, more preferably 20 to 50% or 55 to 70%, more preferably 20 to 50%, or 55 to 66% Most preferably, but not limited thereto.
The separation may be carried out using a normal silica gel (silicagel) or a reversed phase ODS (octadecylsilyl silica gel), but any method capable of gradient by concentration can be used.
The extraction temperature is preferably 20 to 100 ° C, more preferably 20 to 40 ° C, most preferably room temperature, but is not limited thereto. Further, the extraction time is preferably 10 to 48 hours, more preferably 12 to 36 hours, but is not limited thereto.
The fraction may be obtained by repeating the fractionation process from the extract of Artemisia capillaris 1 to 5 times, preferably 3 times, followed by fractionation and concentration under reduced pressure, but it is not limited thereto.
When the extract of Artemisia princeps or its fractions is prepared by the method of the present invention as described above, the active ingredient is prevented from being dispersed and a larger amount of the active fraction can be obtained. Thus, the antiseptic, antioxidant, It is possible to effectively obtain an extract or fraction which can be expressed.
Specifically, when the extract of Artemisia officinalis is extracted with a mixture of water and ethyl acetate, the water layer contains water-soluble components and the ethyl acetate layer contains a fat-soluble component. Means that the components are mostly lipophilic components. In addition, when only the ethyl acetate layer is separated and extracted with a mixed solution of methanol and hexane, hexane will contain lipid components, and the methanol layer will contain components with slightly higher polarity such as flavonoid and lignan, Means that the component exhibiting activity is a component having a somewhat higher polarity among fat-soluble components.
On the contrary, when a conventional solvent fractionation method is used, the active ingredients are dispersed in various solvents depending on the polarity, so that when the active ingredients are mostly polarized as in the present invention, a large amount of active ingredients It will be disadvantageous to obtain.
Accordingly, the production method of the present invention is an effective method for easily obtaining a larger amount of active ingredient by overcoming the limitations of the existing methods in the separation of active ingredients using Artemisia japonica.
Various formulation examples and formulation examples including the extract according to the present invention are described below, but the present invention is not intended to be limited but is to be specifically described.
Preparation Example 1. Preparation of tablets
Examples of the extract of Artemisia princeps or its fractions ... 100 mg
Starch ................................................. ...... 50 mg
Lactose ................................................. ...... 50 mg
Magnesium stearate ............................. 5mg
The above components were mixed and tablets were prepared by a wet granulation method or a dry granulation method according to a conventional method for producing tablets.
Formulation Example 2. Preparation of capsules
The extract of Artemisia princeps or its fractions in the examples ........ 0 mg
Starch ................................................. ... 50mg
Lactose ................................................. ... 50mg
Talc ................................................. ... 1mg
Magnesium stearate ............................. 5mg
The above components were mixed and capsules were prepared according to the conventional preparation method of capsules.
Formulation Example 3. Preparation of a liquid preparation
The extract of Artemisia princeps or its fractions of the examples ... 500 mg
Isolation Party ................................................ ..10g
saccharose................................................. ..... 10g
Lemon flavor ................................................ ... Appropriate amount
Purified water was added to the whole .............................. 50 ml
The above components were mixed according to a conventional method for preparing a liquid preparation, filled in a brown bottle, and sterilized to prepare a liquid preparation.
Formulation Example 4. Preparation of injection
The extract of Artemisia princeps or fraction thereof of the example ... 50 mg
Sodium Metabisulfite ........................... 2.6mg
Methylparaben ...................................... 0.5 mg
Propylparaben .................................... 0.1 mg
Sterilized distilled water for injection ................................ Appropriate amount
The above ingredients were mixed and adjusted to 2 ml in a conventional manner, filled in an ampoule and sterilized to prepare an injection.
Formulation Example 5. Preparation of beverage
Artemisia extract or its fractions of the examples: 100 mg
Vitamin B2 ................................................ 5 mg
Vitamin B6 ................................................ 5 mg
Vitamin C ................................................ ... 80 mg
Dietary fiber .............................................. 1000㎎
Liquid fructose ............................................ 10,000㎎
Emulsifier ................................................ 100 Mg
Lemon flavor ................................................ .
Purified water................................................. Proper amount
The above components were mixed to make a volume of 50 ml, the mixture was passed through a 3-μm filter, and the resulting filtered mixture was first sterilized at 90 to 93 ° C for 20 seconds, filled in a 50 ml bottle, Followed by secondary sterilization for 20 minutes to prepare a beverage product.
Formulation Example 1. Flexible lotion (skin lotion)
Artemisia sp. Extract or fractions thereof of the embodiment: 2.0
Glycerin ............................... 3.5
Oleyl alcohol ...................... 1.5
Ethanol ............................ 5.5
Carboxyl vinyl polymer 1.0
Butylene glycol .................... 2.0
Propylene glycol .................. 2.0
Preservatives, fragrances .....................
Purified water ...........................
Total ............................... 100
Flexible lotion was prepared according to the above composition in a conventional manner (unit weight%).
Formulation Example 2. Nourishing lotion (milk lotion)
Artemisia sp. Extract or fraction thereof of the examples
glycerin................................................. .3.0
Butylene glycol ...............................................
Propylene glycol ........................................ 3.0
Carboxyvinyl polymer .................................. 0.1
Wax ................................................. 4.0 ... 4.0
Caprylic / Capriculiglyceride ........... 5.0
Squalane ........................................ 5.0
Sorbitac esquioleate ........................... 1.5
Cetearyl Alcohol ................................. 1.0
Triethanolamine ................................... 0.2
Preservatives, fragrances ....................................
Purified water ........................................... Remainder
Total: 100
Nutrition lotion was prepared according to the above composition in a conventional manner (unit weight%).
Formulation Example 3. Nourishing cream
Artemisia sp. Extract or fractions thereof in the examples ...... 2.0
Glycerin ......................................... 3.5
Butylene glycol ....................................... 3.0
Liquid paraffin ....................................... 7.0
Beta Glucan ....................................... 7.0
Carbomer ........................................... 0.1
Caprylic / capric wriglyceride ...
Squalane ......................................... 5.0
Cetearyl Glucoside ........................... 1.5
Sorbitan stearate ............................ 0.4
Triethanolamine ................................... 0.1
Preservative, fragrance ....................................
Purified water .......................................... Remaining amount
Total ..................................... 100
Nutritive creams were prepared according to the above composition in a conventional manner (unit weight%).
Formulation Example 4. Pack
Artemisia sp. Extract or fractions thereof in the examples ........ 2.0
Glycerin ..................................... 4.0
Polyvinyl alcohol ........................... 15.0
Hyaluronic Acid Extract 5.0
Beta Glucan ................................. 7.0
Allantoin ....................................... 0.1
Nonyl phenyl ether ......................... 0.4
Preservative, fragrance ..............................
Purified water ......................................... Remaining amount
system................................................. ... 100
A pack was prepared according to the above composition in a conventional manner (unit weight%).
Formulation Example 5. Pharmaceutical preparation for local administration (patch)
Artemisia sp. Extract or fractions thereof in the examples 2.0
Beta-1,3-glucan ................................... 3.0
Diethylamine ............................................... 0.7
Sodium Sulfate ................................... 0.1
Polyoxyethylene lauryl ether (E.O. = 9) 1.0
Polyhydroxyethylene cetyl stearyl ether (Cetomacrogol 1000) 1.0
Viscous paraffin oil
Caprylic acid ester / capric acid ester (Cetiol LC) 2.5
Polyethylene glycol 400 .................................... 3.0
Polyacrylic acid (Carbopol 934P) ..................... 1.0
Purified water................................................. ........ Remainder
system................................................. ......... 100
According to the above composition, a medicament for topical administration was prepared by a conventional method (unit% by weight).
Formulation Example 6. Soap
Examples of the extract of Artemisia princeps or its
maintain................................................. ....... Appropriate amount
Sodium hydroxide ......................................... Appropriate amount
Sodium chloride ............................................. Appropriate amount
Spices................................................. .......handful
system................................................. ............. 100
A soap was prepared according to the above composition in a conventional manner (unit weight%).
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are merely illustrative of the present invention and that the scope of the present invention is not construed as being limited by these embodiments.
Example 1. Preparation of Artemisia cinerea extract
Artemisia Capillaris ; AC; After 1 ~ 2 times of washing with distilled water and drying for 1 ~ 2 days at 20 ~ 60 ℃, 1,500 ml of alcohol, methanol or distilled water was added to 1,000 g of dried eggplant. And extracted at room temperature for 12 to 36 hours. Thereafter, the mixture was naturally filtered using a filter paper having a pore size of 5 쨉 m or less. The filtrate was concentrated by using a vacuum concentrator to a Brix of about 3 to 6 as measured by a sugar content meter, lyophilized, And homogenized to obtain 96.7 g of Artemisia sp.
Example 2. Preparation of fractionated organic solvent
2000 ml of ethyl acetate mixed solution (1000 ml of ethyl acetate, 1000 ml of water) was added to 96.7 g of the extract of Artemisia japonica extract (ethanol extract) of the present invention prepared through the alcohol (ethanol) in Example 1 at room temperature for 12 to 36 hours The ethyl acetate fraction and the water fraction were separated and filtered to prepare the ethyl acetate fraction and water fraction of the present invention, respectively.
The obtained ethyl acetate fraction (52.2 g) was further suspended in 1,400 ml of 90% methanol mixed solution (700 ml of 90% methanol, 700 ml of hexane) and extracted at room temperature for 12 to 36 hours. The residue was divided into a 90% methanol layer and a hexane layer The fractions were respectively separated / filtered to produce the methanol fraction and hexane fraction of the present invention.
Example 3. Preparation of fractionated fractions (Fr. 1 to Fr. 7) of organic solvent fraction
In order to obtain a sub-fraction exhibiting activity among the methanol fractions prepared in Example 2, 5 g of a 90% methanol fraction was used as a solvent, and a YMC-DispoPack AT SIL-25 column was used as a solvent containing ethyl acetate and hexane as a solvent. MPLC (LC-Forte / R, YMC) was performed. Starting with a solvent (20% ethyl acetate solution) with a ratio of ethyl acetate and hexane of 20:80 and gradually increasing the amount of ethyl acetate in the solvent until the concentration of ethyl acetate reaches 100% The solvent was flowed at a flow rate of 30 ml / min for 60 minutes. At this time, three wavelengths of 254 nm, 285 nm, and 356 nm were detected as the UV wavelength, and each fraction was fractionated based on the eluted peak to obtain a total of 7 fractions. This is named Fr.1 to Fr.7, and the time and solvent concentration of each fraction are shown in the table below.
The fractions isolated in each step were concentrated with a vacuum concentrator, lyophilized and homogenized with a mixer in the absence of moisture. The process of obtaining the extract of the present invention and its fractions is shown in FIG.
Experimental Example 1. Measurement of Anti-inflammatory Activity of Artemisia capillaris Extract
Induction of nitric oxide by induction of inflammatory reaction was measured by greiss reagent after stabilization of nitrite to nitrate. The inhibitory activity of nitric oxide (NO), an indicator of cellular inflammation, was determined by measuring the amount of nitrate produced during LPS - induced inflammation. Specifically, RAW264.7 cells were cultured in 96-well plates at a cell density of 5
As a result, LPS was a control group that induced inflammation reaction. Normal cells were not treated with LPS, and thus, NO inhibitory effect was not obtained. In addition, (See FIG. 2). From these results, it was found that the extract of Artemisia princeps of the present invention exhibits anti-inflammatory activity.
Experimental Example 2. Antioxidant activity measurement of Artemisia sp.
The antioxidative activity of free radical scavenging ability was measured by confirming the ability of reducing or canceling the free radical DPPH, that is, the oxidation inhibiting activity. DPPH was used as a measure of antioxidant activity because it was decolored and reduced by a sample with a relatively stable free radical having a deep purple color. L-ascorbic acid was used as a positive control and DPPH (1,1-diphenyl-2-picryl hydrazyl) method was used for comparison. 200 μl of 0.2 mM DPPH ethanol solution was successively diluted 2-fold with the extract of Artemisia japonica extract, reacted at room temperature for 30 minutes, and the absorbance at 517 nm was measured. The free radical scavenging activity was determined using the following equation, and the electron donating ability was expressed by the absorbance reduction rate of the sample solution addition group and no addition group.
Free radical scavenging ability (%) = (1 - absorbance of sample addition group / absorbance of no addition group)
As a result, DPPH radical scavenging activity was increased in a concentration dependent manner when the extract was treated by concentration, and about 84% of radical scavenging activity was observed at 100 ㎍ / ml treatment concentration. (See Fig. 3). Thus, it was found that the extract of Artemisia princeps of the present invention exhibits antioxidant activity.
Experimental Example 3. Measurement of whitening activity of Artemisia princeps
(1) preparation of cells
In the experiment for measuring whitening activity according to the present invention, melanoma-producing mouse-derived melanoma cells (B16F10 mouse melanoma cell) were used. The culture medium was 10% (v / v) FBS, 100 units / ml penicillin and 100 α-MEM containing streptomycin was used. The culture conditions were 5% CO 2 and 37 ° C.
(2) Cytotoxicity measurement
B16F10 cells were cultured in 96-well microplates at a concentration of 1 × 10 3 cells / well. After the cells were cultured for 48 hours, the supernatant was removed. MTT solution (100 μl) was treated at 36 ° C for 4 hours according to the measurement method of MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) and then the culture solution was removed and 50 μl of DMSO was treated And the absorbance was measured with an absorbance meter (ELISA) at 540 nm. The measured values were calculated by the following formula.
Cytotoxicity (%) = (1-absorbance of sample addition group / absorbance of no addition group)
As a result of comparing the survival rate of cells treated with B16F10 cells at various concentrations, the survival rate of B16F10 cells was not decreased, and thus it was confirmed that the B16F10 cells were not toxic to Melanoma cells (see FIG. 4).
(3) Measurement of intracellular melanin concentration
B16F10 cells were cultured in 6-well microplates at a concentration of 2 × 10 4 cells / well, and the samples were cultured for 48 hours, and the supernatant was removed. Cells were collected in tubes and melanin was eluted from the cells with NaOH and absorbance was measured at 405 nm.
When B16F10 cells were treated with the extract of Artemia japonica extract at different concentrations, melanocyte production was induced by stimulation of melanoma cells with α-MSH (Melanocyte Stimulating Hormone) Melanin production was inhibited. When the extract was administered at a concentration of 12.5 / / ml or more, the effect of inhibiting melanogenesis was excellent and the effect was excellent at a concentration of 12.5-100 / / ml, preferably 50-100 / / ml. In particular, when the concentration of Artemisia sp. Extract was 50 μg / ml, melanogenesis was suppressed to a degree similar to that of the control without α-MSH treatment (see FIG. 5). In addition, when melanin was extracted from cells and expressed as a concentration value, it was confirmed that melanogenesis was inhibited in a concentration-dependent manner (see FIG. 6).
(4) Measurement of intracellular tyrosinase activity
B16F10 cells were cultured in 6-well microplates at a concentration of 2 × 10 4 cells / well, and the samples were cultured for 48 hours, and the supernatant was removed. The cells dissolved in the buffer were reacted with L-DOPA (L-3,4, -dihydroxyphenylalanine) and absorbance was measured at 475 nm.
As a result of measuring the degree of inhibition of the enzymatic activity of the extract of Artemisia cinerea against the enzyme tyrosinase (tyrosinase), which is the most related to melanin formation in melanoma cells, melanoma cells were stimulated with α-MSH to induce melanogenesis , Tyrosinase activity was also increased (about 157% of tyrosinase activity was found in α-MSH treatment), and tyrosinase activity was inhibited in a concentration-dependent manner upon treatment with Artemisia sp. Extract (tyrosinase activity at a concentration of 50 μg / and about 107% when melanin without α-MSH was taken as 100%) (see FIG. 7). When the extract was administered at a concentration of 12.5 / / ml or more, the effect of inhibiting tyrosinase activity was excellent and the effect was excellent at a concentration of 12.5-100 / / ml, preferably 50-100 / / ml.
(5) Summary of results
As shown in Experimental Examples 1 to 3 of the present invention, the extract of Artemisia princeps of the present invention showed anti-inflammation, antioxidant or skin whitening activity, and the composition containing it as an active ingredient contained 12.5 to 100 ㎍ / ml, preferably 25 to 100 占 퐂 / ml, more preferably 50 to 100 占 퐂 / ml, exhibits excellent anti-inflammatory, antioxidative and whitening activity. It was confirmed that the same or similar effect was obtained at a concentration of 100 / / ml or more in the case of treatment with 100 / / ml, and the above-mentioned preferable concentration was in accordance with the concentration used in cell treatment in vitro , The present invention is not limited thereto.
Experimental Example 4. Measurement of whitening activity of organic solvent fraction
In order to confirm whether each of the organic solvent fraction (ethyl acetate fraction, water fraction, methanol fraction, and hexane fraction) of the present invention produced in Example 2 exhibited similar activity to the extract of Artemisia princeps, The intracellular melanin concentration was measured to confirm the whitening activity.
Specifically, the mouse-derived melanoma cells (B16F10 mouse melanoma cell) producing melanin were used for the measurement of whitening activity, and the culture medium was prepared by adding 10% (v / v) FBS, 100 units / ml penicillin and 100 unit / Α-MEM containing mitomycin was used. The culture conditions were 5% CO 2 and 37 ° C. For measurement of intracellular melanin concentration, B16F10 cells were cultured in a 6-well microplate at a concentration of 2 × 10 4 cells / well, and each sample (extract or fraction) was added to each concentration and cultured for 48 hours to remove the supernatant . Cells were collected in tubes and melanin was eluted from the cells with NaOH and absorbance was measured at 405 nm.
(1) Ethanol extract, (2) Ethyl acetate fraction, (4) Ethanol extract, (2) Ethyl acetate fraction, (3) Water fraction, ) Methanol fraction inhibited melanogenesis of cells in a concentration-dependent manner. In contrast, (3) water fraction and (5) hexane fraction did not inhibit the melanin production inhibitory activity (see FIGS. 8 and 9) .
The IC 50 value refers to the inhibitory concentration 50 (fifty), the inhibition concentration or the inhibition concentration. When the size of any reaction A is assumed to be 100%, the size of reaction A is reduced to 50% If possible, the concentration of B at that time is called the IC 50 of B for reaction A. If the IC 50 value is 1.4 μg / ml, it means that only 1.4 μg / ml is required to inhibit any reaction to 50%. As a result, the smaller the IC 50 value, the stronger the ability to inhibit the reaction. The IC 50 values of (1) ethanol extract, (2) ethyl acetate fraction and (4) methanol fraction showing whitening activity were compared and the results are shown in the table below.
As can be seen from the above results, the extract was prepared by extracting Artemisia japonica with ethanol and then sequentially extracted with a mixed solution of ethyl acetate and water and a mixed solution of 90% methanol and hexane. As a result, the ethyl acetate extract had the same weight 2.15 times, and the methanol fraction exhibited a high whitening activity (ability to inhibit melanin formation) of 3.74 times as much as the same weight.
As a result of TLC (Thin Layer Chromatography), it was confirmed that a substance expected to be an active ingredient exists only in a fraction exhibiting whitening activity upon irradiation with UV at a wavelength of 365 nm (see FIG. 10 (c)).
In conclusion, the ethyl acetate fraction and the methanol fraction thereof of the present invention show much higher whitening activity than the Artemisia sp. Extract, which can be expected because the active ingredient is concentrated.
Experimental Example 5. Measurement of whitening activity of fractionated fractions of Artemisia sp.
In order to confirm whether each of the fractions (Fr. 1 to Fr. 7) of the fragrant organic solvent fraction of the present invention produced in Example 3 exhibited similar activity to the extract of Artemisia princeps or its organic solvent fraction, The intracellular melanin concentration was measured in the same manner as in the method described in (3) to confirm whitening activity.
As a result, it was confirmed that whitening activity (inhibitory activity on melanin formation) was observed in
In conclusion, the extract of Artemisia japonica extract or its organic solvent fraction of the present invention exhibits excellent whitening activity. Particularly, the fractions obtained by sequentially treating the ethanol extract of Artemisia wisdomini with ethyl acetate and 90% methanol are mixed with 20% to 67% of ethyl It was found that the supernatant fractions obtained by further separation using acetate as a solvent showed the best activity. In particular, it was confirmed that the activity of inhibiting melanin formation was very high in Fr.1 to Fr3 and Fr.5 in which the concentration of ethyl acetate was 20 to 50% or 55 to 66%.
In addition, when compared with 500 ug arbutin used as a positive control, it was confirmed that melanin was hardly produced even when the fraction of the present invention was treated with 30 ug of 17-fold lower concentration. Thus, the fraction according to the present invention has a low concentration And thus it can be used effectively as an active ingredient of various compositions such as cosmetics, soaps, medicines or foods.
Having described specific portions of the present invention in detail, it will be apparent to those skilled in the art that this specific description is only a preferred embodiment and that the scope of the present invention is not limited thereby. It will be obvious. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.
Claims (22)
1) extracting Artemisia capillaris with a solvent selected from water, methanol, ethanol or a mixed solvent thereof;
2) extracting the above extract with a solvent of water and ethyl acetate having a concentration of ethyl acetate of 40 to 70% to obtain an ethyl acetate fraction;
3) extracting the ethylacetate fraction with a solvent mixture of methanol and hexane having a methanol concentration of 70 to 95% to obtain a methanol fraction; And
4) The methanol fraction is separated using a mixed solvent of ethyl acetate and hexane as a solvent to obtain a fraction having a concentration of ethyl acetate in the solvent of 10 to 70%.
Wherein the mixed solution of water and ethyl acetate in step 2) has a concentration of ethyl acetate of 50 to 60%.
Wherein the mixed solution of water and ethyl acetate in step 2) has a concentration of ethyl acetate of 50%.
The mixture of methanol and hexane in step 3) has a methanol concentration of 80 to 90%.
Wherein the methanol and hexane mixed solution of step 3) has a methanol concentration of 90%.
Wherein the composition is a cosmetic composition.
(2) extracting the dried material with water, a C1-C2 alcohol, or a mixed solvent thereof;
(3) Extracting the extract obtained in the step (2) with a mixed solvent of ethyl acetate and water having a concentration of ethyl acetate of 40 to 70% as a solvent;
(4) extracting a mixed solution of methanol and hexane having a methanol concentration of 70 to 95% with a solvent in the extract obtained in the step (3);
(5) A method for producing an extract of Artemisia sp., Wherein the extract obtained in step (4) is obtained by fractionating a mixture of ethyl acetate and hexane with a solvent and obtaining a fraction having a concentration of ethyl acetate in the solvent of 10 to 70% Gt;
Wherein the separation of step (5) is carried out using a normal silica gel (silicagel) or reverse phase ODS (octadecylsilyl silica gel).
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KR102011837B1 (en) * | 2018-10-10 | 2019-10-21 | 주식회사 네오캠코리아 | Cosmetic composition comprising extract of Artemisia capillaris using heat-tinc extract method and low-temperature ripening |
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CN109952108A (en) * | 2016-11-15 | 2019-06-28 | 韩国科学技术研究院 | Including Artemisia annua extract as effective component for improving the composition and preparation method thereof of skin disease |
KR20180063388A (en) | 2016-11-17 | 2018-06-12 | 인제대학교 산학협력단 | Compositions for Preventing or Treating Fulminant Hepatic Failure Comprising Water Soluble Extraction of Artemisia capillaris Thunb. |
KR20180062682A (en) * | 2016-12-01 | 2018-06-11 | 인제대학교 산학협력단 | Aqueous extract of artemisia capillaris, and use and preparation method thereof |
KR102196051B1 (en) * | 2019-01-25 | 2020-12-29 | (주)월드코스텍 | Skin functional composition containing fermented artemisia capillaris |
KR102192004B1 (en) * | 2019-06-24 | 2020-12-16 | 김영지 | Shampoo composition for preventing hair loss and improving state of hair |
KR102400179B1 (en) * | 2020-08-31 | 2022-05-25 | 주식회사에이치엔비랩스 | Cosmetic composition antimicroboal, antioxidation, whitening or anti-inflammation comprising artemisia capillaris thunberg and olive extract |
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