JP6490342B2 - Anti-skin aging agent containing Shiranui Chrysanthemum extract - Google Patents

Description

  The present invention relates to an anti-skin aging agent comprising a Shiranui chrysanthemum extract.

  It is well known that various skin symptoms occur in the skin due to various factors such as aging, sunlight (ultraviolet rays), drying, oxidation, and saccharification, resulting in decreased tension and elasticity, wrinkles and sagging. ing. These skin symptoms are regarded as skin aging. Such a skin aging phenomenon is considered to be one of the major causes of reduction or degeneration of collagen and elastin which are main components of the extracellular matrix in the dermis. For example, the physiological function of skin cells decreases with aging, and the aging of the skin is caused by the decrease / denaturation of collagen and elastin and the resulting decrease in extracellular matrix function. On the other hand, photoaging, which is a chronic UV injury, enhances the activity of matrix metalloprotease by active oxygen generated in the skin by exposure to UV rays, denatures collagen, elastin, etc. present in the skin, It is supposed to cause skin sagging and wrinkles. In recent years, glycation of collagen and elastin occurs in skin due to various factors such as ultraviolet rays, and it is known that the presence of this glycated collagen and glycated elastin reduces the function of the extracellular matrix in the dermis and causes skin aging. It is like that. For this reason, in order to prevent or improve skin aging, measures against reduction or degeneration of collagen and elastin in the skin are important issues.

  Collagenase inhibitory activity, elastase inhibitory activity, and antioxidant activity are considered to be particularly closely related to the prevention of skin aging. Collagenase and elastase are one of a group of enzymes (matrix metalloproteases) that destroy the extracellular matrix.

  As herbal medicines having collagenase inhibitory activity, for example, a rhizome solvent extract (see Patent Literature 1), a pine bark extract (see Patent Literature 2), etc. of the genus Bergenia ligrata have been reported. Further, as herbal medicines having elastase inhibitory activity, for example, an extract of Totonico (see Patent Document 3), a jojoba leaf extract (see Patent Document 4), and the like have been reported. Further, as herbal medicines having antioxidant activity, for example, powders and / or extracts (see Patent Document 5) of Asteraceae plants are reported. However, the anti-skin aging effect of these herbal medicines is not sufficient. Therefore, in terms of safety to human skin, further herbal medicines that have strong skin aging prevention effects such as collagenase inhibitory activity, elastase inhibitory activity, and antioxidant activity so that they are derived from natural products and can be used at low concentrations. Is required.

  Shiranui chrysanthemum (Chrysanthemum indicam x Erigeron annuus) is a kind of Asteraceae plant, and is a cultivar cultivated in part of Shiranui, Uki City, Kumamoto Prefecture. Shiranui chrysanthemum is morphologically different from existing asteraceae plants and is recognized as a new species. The general form of Shiranui chrysanthemum is not necessarily limited to the following, but the stem is about 50-100cm and slightly woody, the leaves are dark green and have alternate petioles, and the leaf blades are oval in shape The wings are split into five, and the cracks have teeth and are 3-6 cm long and 2.5-5 cm wide. Shiranui chrysanthemum is known to give white flower heads with a diameter of 2.5-3.5cm in the form of bunches from mid-November to early December.

  The dried petals of Shiranui Chrysanthemum, decocted with water or sake, have been used as a folklore medicine for a long time in anticipation of effects on cancer and diabetes. Moreover, about the efficacy in humans of the petal extract and leaf extract of Shiranui Chrysanthemum, the production promotion effect of tumor necrosis factor (TNF-α) (Non-patent document 1), the histamine release inhibitory effect (Non-patent document 2), It has been reported. However, other effects of Shiranui Chrysanthemum extract are not yet fully known.

JP 2004-315492 A JP 2003-238426 A Japanese Patent Laid-Open No. 11-147832 JP 2003-48812 A JP 2004-155961 A

Kobayashi et al., “TNF-α production promoting effect of Shiranui Hime Chrysanthemum extract”, Journal of Japanese Society for Food Science and Technology, Japanese Society for Food Science and Technology, August 2006, 53, 8, 430 Yamada et al., “Histamine Release Suppressing Effect of Petal and Leaf Extract of Shiranui Hime Chrysanthemum”, Journal of the Japan Society for Food Science and Technology, Japan Society for Food Science and Technology, August 2012, 59, 8, 394

  An object of the present invention is to provide an anti-skin aging agent.

  As a result of intensive studies to solve the above problems, the present inventors have found that the Shiranui Chrysanthemum extract has an excellent anti-skin aging action that contributes to the prevention or improvement of skin aging, and completes the present invention. It came to.

That is, the present invention includes the following.
[1] An anti-skin aging agent containing an extract of Chrysanthemum indicam × Erigeron annuus as an active ingredient.
[2] The anti-skin aging agent according to the above [1] for preventing skin aging.
[3] The anti-skin aging agent according to the above [2], which is for skin aging prevention based on at least one selected from the group consisting of collagenase inhibitory action, elastase inhibitory action, antioxidant action, and anti-glycation action.
[4] The anti-skin aging agent according to [1] above for improving skin aging.
[5] The anti-skin aging agent according to the above [4], which is for improving skin aging based on at least one of a collagen production promoting action and an elastin production promoting action.
[6] The anti-skin aging agent according to any one of [1] to [5], which is an external preparation for skin.
[7] The anti-skin aging agent according to any one of [1] to [6], wherein the Shiranui Chrysanthemum extract is an alcohol extract or a water extract.
[8] The anti-skin aging agent according to any one of the above [1] to [7], wherein the Shiranui Chrysanthemum extract is an extract of the above-ground part of Shiranui Chrysanthemum or whole grass.
[9] A collagenase inhibitor containing an extract of Chrysanthemum indicam × Erigeron annuus as an active ingredient.
[10] An elastase inhibitor containing an extract of Chrysanthemum indicam × Erigeron annuus as an active ingredient.
[11] An antioxidant containing an extract of Chrysanthemum indicam × Erigeron annuus as an active ingredient.
[12] An anti-glycation agent containing an extract of Chrysanthemum indicam × Erigeron annuus as an active ingredient.
[13] A collagen production promoter containing an extract of Chrysanthemum indicam × Erigeron annuus as an active ingredient.
[14] An elastin production promoter containing an extract of Chrysanthemum indicam × Erigeron annuus as an active ingredient.
[15] A cosmetic comprising the agent according to any one of [1] to [14].
[16] A medicament comprising the agent according to any one of [1] to [14] above.

  The anti-skin aging agent according to the present invention can provide an excellent anti-skin aging action that contributes to prevention and improvement of skin aging.

FIG. 1 is a photograph showing the appearance of the Shiranui Chrysanthemum. FIG. 2 is a diagram showing the collagenase activity inhibitory action of the Shiranui Chrysanthemum extract. FIG. 3 is a diagram showing the elastase activity inhibitory action of the Shiranui Chrysanthemum extract. FIG. 4 is a diagram showing the antioxidant effect of the Shiranui Chrysanthemum extract. The triangle indicates the above-ground extract, the diamond indicates the whole plant extract, and the square indicates the tea extract. FIG. 5 is a diagram showing the anti-glycation effect of Shiranui Chrysanthemum extract. FIG. 6 is a diagram showing the collagen production promoting action of the Shiranui Chrysanthemum extract. FIG. 7 is a diagram showing the elastin production promoting action of the Shiranui Chrysanthemum extract.

  Hereinafter, the present invention will be described in detail.

The present invention relates to an anti-skin aging agent containing a Shiranui chrysanthemum extract as an active ingredient.
Chrysanthemum indicam x Erigeron annuus, which is the raw material of the above extract, is a type of Asteraceae plant cultivated in a part of Shiranui, Uki City, Kumamoto Prefecture. It is an intergeneric hybrid of two species of Asteraceae. The Shiranui Chrysanthemum is also called the Shiranui Hime Chrysanthemum or Omi Chrysanthemum. A photograph is shown in FIG. 1 as an example of the appearance of Shiranui Chrysanthemum. Shiranui chrysanthemum generally blooms in autumn in the above-mentioned cultivation areas.

  The Shiranui Chrysanthemum extract used in the present invention may be an extract of whole Shiranui Chrysanthemum, or a part of the Shiranui Chrysanthemum, for example, the above-ground part, flowers (including buds), petals, leaves, stems, etc. , And any combination thereof, but a part of or a whole herb extract containing flowers or petals or leaves is preferred. More preferably, the above-ground extract of Shiranui Chrysanthemum is particularly preferred. The above-ground part of Shiranui Chrysanthemum contains flowers or petals, as well as leaves and stems. The above-ground part of Shiranui Chrysanthemum may further include stamens, pistils, gargles, seeds and the like. The whole plant of Shiranui Chrysanthemum refers to the whole plant body including the above-ground part and underground part (mainly root) of Shiranui Chrysanthemum. The whole Shiranui chrysanthemum contains flowers or petals and leaves, stems and roots.

  The Shiranui Chrysanthemum extract may be an extract obtained by any extraction technique, but is preferably an alcohol extract or a water extract. In the present invention, the alcohol extract means an extract obtained from Shiranui Chrysanthemum using anhydrous alcohol or an aqueous alcohol solution. In the present invention, the water extract means an extract obtained from Shiranui Chrysanthemum using water (for example, but not limited to, cold water, room temperature water, hot water or hot water) or a buffer solution.

  The Shiranui Chrysanthemum extract can be obtained by immersing the whole plant or part of the Shiranui Chrysanthemum (for example, the above-ground part, flowers, etc.) in an extraction solvent and eluting plant components into the extraction solvent. The whole or part of Shiranui Chrysanthemum may be used as it is for extraction, or used for extraction after processing suitable for extraction processing, for example, drying, cutting or crushing to an appropriate size, etc. Also good. In terms of extraction efficiency, it is preferable that the whole or part of the Shiranui chrysanthemum is subjected to an extraction treatment after drying and pulverization. Extraction solvents include, but are not limited to, alcohol, water, buffer, dilute acid, and dilute alkali, and any combination or mixed solvent thereof. In the case of an alcohol extract, alcohol (anhydrous alcohol) or an aqueous alcohol solution (a mixed solvent of alcohol and water) can be used as an extraction solvent. The alcohol may be a monohydric alcohol or a polyhydric alcohol. Specific examples of the monohydric alcohol include methanol, ethanol, propyl alcohol, butyl alcohol, isobutyl alcohol, and benzyl alcohol. Examples of the polyhydric alcohol include ethylene glycol, propylene glycol, glycerin, and 1,3-butylene glycol. When an aqueous alcohol solution is used as the extraction solvent, the alcohol concentration is preferably 50% or less, for example, 10 to 40%. For example, an aqueous ethanol solution having a concentration of 10 to 40%, an aqueous solution of 1,3-butylene glycol having a concentration of 10 to 40% can be suitably used. Absolute ethanol and 1,3-butylene glycol (anhydrous) are also particularly suitable as extraction solvents.

  For example, the extraction solvent is preferably 1 to 200 parts by weight, more preferably 2 to 100 parts by weight, still more preferably 5 to 100 parts by weight, for example 5 to 50 parts by weight, based on 1 part by weight (dry weight) of Shiranui Chrysanthemum. In addition, the extraction can be performed by immersing Shiranui Chrysanthemum in an extraction solvent for a certain period of time, but is not limited to this method. Those skilled in the art can appropriately adjust the extraction temperature and the extraction time in the extraction solvent in consideration of the type and amount of the extraction solvent. The extraction temperature (the temperature of the extraction solvent) is not limited, but is usually a boiling point of more than 0 ° C. to pressure, preferably room temperature (15 to 30 ° C.) to boiling point under pressure, more preferably It can be 20 ° C to 100 ° C, for example 50 ° C to 70 ° C. The extraction time (time for immersion in the extraction solvent) varies depending on the type of extraction solvent and the extraction temperature, but is usually 30 minutes to 4 weeks, preferably 1 hour to 2 weeks, more preferably 3 hours to 5 days, for example 10 It can be between 48 hours and 48 hours. As a suitable example, in the case of water extraction, the extraction time can be set to, for example, 1 to 2 weeks, preferably 10 to 48 hours at an extraction temperature of 20 to 70 ° C., for example, 60 ° C. In the case of alcohol extraction using absolute ethanol or an aqueous ethanol solution (hydrous ethanol) having a concentration of 10 to 40%, the extraction time is 20 to 70 ° C., for example 60 ° C., for example 1 to 2 weeks, preferably 10 The time can be from 48 hours. Further, in the case of alcohol extraction using 1,3-butylene glycol (anhydrous) or an aqueous solution of 1,3-butylene glycol having a concentration of 10 to 40%, the extraction time is 20 to 100 ° C., for example 60 ° C., for example 1 hour. Up to 2 weeks, preferably 10 to 48 hours.

  The extract containing the Shiranui Chrysanthemum component extracted in this way may be used as it is as the Shiranui Chrysanthemum extract, but is generally applied to the extract as long as it does not significantly affect its anti-skin aging effect. The usual processing to obtain may be performed. For example, the extracted liquid containing the Shiranui chrysanthemum component may be purified by a known purification method such as centrifugation and filtration of the precipitate, or purification for deodorization and decolorization by activated carbon column filtration or the like. Processing may be performed. Moreover, you may perform a concentration process, a dilution process, or a solvent exchange process with a conventional method about the extracted liquid containing the Shiranui chrysanthemum component. The extract containing the extracted Shiranui chrysanthemum component and its processed product may be dried by any drying technique such as a thermal drying method such as a spray drying method or a freeze drying method to obtain a dried product. In the present invention, an extract containing such an extracted Shiranui chrysanthemum component or a processed product thereof (for example, a dried product such as a lyophilized product including a vacuum lyophilized product, a purified product, a concentrate, a diluted product, an extraction product) A solution in a solvent other than the solvent, or a combination thereof) is collectively referred to as the Shiranui Chrysanthemum extract.

  The Shiranui Chrysanthemum extract thus obtained exhibits high collagenase inhibitory activity, high elastase inhibitory activity, high antioxidant activity, high antiglycation activity, high collagen production promoting activity, and high elastin production promoting activity, as shown in the Examples below. . All of these activities are known as anti-skin aging activities. Therefore, the Shiranui Chrysanthemum extract according to the present invention can be used as an anti-skin aging agent. That is, this invention provides the anti-skin aging agent which contains the Shiranui chrysanthemum extract which concerns on this invention as an active ingredient. Here, “anti-skin aging” means the effect of preventing or improving skin aging, particularly deterioration of the extracellular matrix of the skin.

  Collagenase inhibitory activity, elastase inhibitory activity, antioxidant activity, anti-glycation activity, collagen production promoting activity, and elastin production promoting activity of the Shiranui Chrysanthemum extract according to the present invention can be measured and evaluated by conventional methods. Specifically, each activity can be measured and evaluated as described in Examples described later.

  In particular, enhancement of collagenase inhibitory activity, elastase inhibitory activity, and antioxidant activity is effective in preventing skin aging, particularly photoaging. In order to prevent photoaging, it is important to eliminate active oxygen generated by UV exposure and to inhibit matrix metalloproteases (especially collagenase and elastase) whose activity is enhanced by active oxygen. Therefore, antioxidants and matrix metalloprotease inhibitors that scavenge active oxygen can be used as effective skin aging inhibitors, particularly skin photoaging inhibitors.

  Further, in the in vivo saccharification reaction, reducing saccharides are combined with proteins to produce protein glycation end products (AGEs; Advanced Glycation End Products). In the skin, glycated collagen, which is an AGE, is deposited in the tissue, weakens the elasticity of the skin, and is involved in wrinkle formation. Skin deterioration due to accumulation of AGEs is enhanced by ultraviolet rays. Therefore, an anti-glycation agent that suppresses the generation / accumulation of AGEs can be used as an effective anti-aging agent for skin, particularly an anti-photo-aging agent for skin.

  That is, the Shiranui Chrysanthemum extract according to the present invention can be effectively used for applications that cause collagenase inhibitory action, elastase inhibitory action, antioxidant action, and anti-glycation action, and in particular, for skin aging prevention based on these actions, In particular, it can be used effectively for preventing skin photoaging. The present invention provides a collagenase inhibitor, an elastase inhibitor, an antioxidant, an anti-glycation agent, and an anti-skin aging agent for preventing skin aging, containing the Shiranui Chrysanthemum extract according to the present invention as an active ingredient. The collagenase inhibitor, the elastase inhibitor, the antioxidant, and the anti-glycation agent according to the present invention may be used on the skin or skin cells (for example, skin fibroblasts) in vivo, or in vitro or ex Skin cells (for example, skin fibroblasts) may be used as an action target in vivo, or cells other than skin cells (for example, skin fibroblasts) (for example, fibroblasts of tissues or organs (such as lungs) other than skin) Alternatively, non-cellular substances such as enzymes (collagenase, elastase) and radicals may be used as the target of action.

  In the present invention, “preventing skin aging” means preventing deterioration of the extracellular matrix of the skin by suppressing the decrease and / or degeneration of collagen and elastin present in the skin. Suppression of collagen and elastin reduction and denaturation can prevent the deterioration of skin's extracellular matrix, thereby suppressing the occurrence of skin aging phenomena such as skin tension and reduced elasticity, wrinkles and sagging.

  On the other hand, collagen and elastin, which are the main components of the extracellular matrix, are reduced and denatured due to factors such as aging and ultraviolet rays, and the function and amount of the extracellular matrix are reduced, resulting in skin aging. In order to maintain the skin in a normal state, it is important to supplement collagen and elastin in the extracellular matrix. Collagen production promoters and elastin production promoters enhance skin aging by enhancing the production of collagen and elastin by cells and increasing the amount of collagen and elastin in the skin, thereby activating the extracellular matrix. It can be used as an agent.

  That is, the Shiranui Chrysanthemum extract according to the present invention can be used effectively for applications that bring about a collagen production promoting action and an elastase production promoting action, and can be used particularly effectively for improving skin aging based on those actions. . The present invention also provides a collagen production promoter, an elastase production promoter, and an anti-skin aging agent for improving skin aging, which contains the Shiranui chrysanthemum extract according to the present invention as an active ingredient. In the present invention, “improving skin aging” means improving the deterioration of the extracellular matrix (skin aging state) by increasing the amount of non-denatured collagen and non-denatured elastin in the skin. The increase in the amount of collagen and elastin activates its function by supplementing the components of the extracellular matrix of the skin, and improves the deterioration of the extracellular matrix (skin aging state), thereby reducing skin tension and elasticity. , Leads to improvement of wrinkles and sagging.

  The anti-skin aging agent, collagenase inhibitor, elastase inhibitor, antioxidant, anti-glycation agent, collagen production promoter, and elastase production promoter according to the present invention may be used orally or parenterally. It can be advantageously used as a skin external preparation.

  The Shiranui Chrysanthemum extract according to the present invention, or an anti-skin aging agent, a collagenase inhibitor, an elastase inhibitor, an antioxidant, an anti-glycation agent, a collagen production promoter, or an elastase production promoter containing the same is added to cosmetics. Can be used. That is, the present invention relates to the Shiranui Chrysanthemum extract according to the present invention, or an anti-skin aging agent, collagenase inhibitor, elastase inhibitor, antioxidant, anti-glycation agent, collagen production promoter, or elastase production promoter containing the same. Cosmetics including are also provided. Such cosmetics according to the present invention can exert their respective anti-skin aging effects when applied to the skin.

  The cosmetic according to the present invention may be a composition in any form of solution, suspension, emulsion, powder, paste, mousse, and gel. The cosmetic according to the present invention may be any cosmetic that can be used in contact with the skin. Specifically, for example, lotion, milky lotion, serum, general cream (face cream, hand cream, body Cream, etc.), face wash (cleansing cream, etc.), pack, shaving cream, sun cream, sun cream, sunscreen lotion, sunscreen lotion, cosmetic soap, foundation, funny, powder, lipstick, lip balm, eyeliner, Eye creams, eye shadows, mascaras, bath cosmetics, shampoos, hair rinses, hair treatments, hair packs, scalp care agents, body rinses, body gels, antiperspirant deodorants, hair dyes, hair cosmetics, and the like. A compounding quantity can be made into the density | concentration of 0.0001-100% by the dry weight of the Shiranui chrysanthemum extract which concerns on this invention in a composition of cosmetics, Preferably it is 0.001-10%. The Shiranui Chrysanthemum extract can be blended in the cosmetic according to the present invention in any form, for example, in the form of liquid, gel, powder, granule, encapsulated body or the like.

  In addition to the Shiranui Chrysanthemum extract, any other component that can be blended in the cosmetic can be blended in the cosmetic according to the present invention. Examples of other ingredients include additives, excipients, and other active ingredients used in cosmetics (for example, other anti-skin aging agents, moisturizers, whitening agents, sunscreen agents, astringents, etc.). However, the present invention is not limited thereto, and those suitable for the use and form of the cosmetic can be arbitrarily selected and used. The cosmetic according to the present invention can be produced by a conventional method by mixing and stirring the raw materials.

  For example, any of the components listed below can be blended with the Shiranui Chrysanthemum extract into the cosmetic according to the present invention.

  Proteins and protein hydrolysates such as collagen, collagen derivatives, collagen hydrolysates, gelatin, gelatin hydrolysates, elastin, elastin hydrolysates, lactoferrin, keratin, keratin hydrolysates, casein, albumin, honey, and royal jelly . Natural polymers such as sodium hyaluronate, xanthan gum, carrageenan, guar gum, alginic acid and salts thereof, pectin, chondroitin sulfate and salts thereof, water-soluble chitin, chitosan derivatives and salts thereof, deoxyribonucleic acid, gum arabic, tragacanth gum, pullulan and the like Derivative.

  Tulip flower extract, Schichenge root extract, Panax ginseng extract, millet bud extract, barley fermented extract, chestnut astringent skin fermented extract, longan seed extract, groundnut seed coat extract, pink rock rose extract, licorice extract, aloe extract, chamomile extract, perilla extract, fruit water Plant extracts such as. Microbial substances such as yeast extract. Seaweed powder and seaweed extract. Animal origin such as placenta extract. Among carboxyvinyl polymers and salts thereof, polyacrylic acid and salts thereof, acidic polymers such as carboxymethyl cellulose and salts thereof, polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, polyethylene glycol, polyvinyl pyrrolidone, nitrocellulose polyvinyl methyl ether, etc. Polymer. Cationic polymers such as cationized chitosan, cationized cellulose, polyethyleneimine, and cationized guar gum. Lower alcohols such as ethanol and isopropyl alcohol. UV absorbers such as paraaminobenzoic acid UV absorbers, salicylic acid UV absorbers, cinnamic acid UV absorbers, anthraniere acid UV absorbers, and benzophenone UV absorbers. UV scattering agents such as titanium oxide and zinc oxide.

  Vitamin A, vitamin B group, vitamin C, L-ascorbyl magnesium phosphate and derivatives thereof, vitamin D group, acetic acid d-α-tocophenol, vitamin E group, folic acid, β-carotene, γ-oryzanol, nicotinic acid, Vitamins such as pantothenic acids, biotins and ferulic acid. Anti-inflammatory agents such as glycyrrhizic acid and its salts, guaiazulene and its derivatives, and allantoin. Antioxidants such as stearic acid ester, nordihydrogua ceretenoic acid, dibutylhydroxytoluene, butylhydroxyanisole, parahydroxyanisole, propyl gallate, sesamol, sesamorin, gossypol. Preservatives such as parabenzoates such as methyl parabenzoate, ethyl parabenzoate, propyl parabenzoate and butyl parabenzoate, sorbic acid, dehydroacetic acid, phenoxyethanol and benzoic acid.

  Metal ion sequestering agents such as edetic acid and edetic acid and its salts, phytic acid, hydroxyethanedisulfonic acid and the like. Polyhydric alcohols such as glycerin, 1,3-butylene glycol and propylene glycol. Amino acids such as L-aspartic acid, DL-alanine, L-arginine, L-cysteine, L-glutamic acid, glycine, and salts thereof. Sugars such as maltitol, sorbitol, xylobiose, N-acetyl-D-glucosamine. Organic acids such as citric acid, lactic acid, α-hydroxyacetic acid, pyrrolidone carboxylic acid and salts thereof. Hydrocarbons such as liquid paraffin, squalane and petrolatum. Fats and oils such as pine seed oil, olive oil, palm oil, evening primrose oil, jojoba oil, castor oil, hydrogenated castor oil. Fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, and behenic acid.

  Higher alcohols such as myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, and behenyl alcohol; Esters such as isopropyl myristate, isopropyl palmitate, cetyl octanoate, glyceryl trioctanoate, octyldodecyl myristate, octyl stearate and stearyl stearate. Phospholipids such as lecithin and its derivatives. Animal and plant-derived lipids such as bovine bone marrow fat and bovine brain lipid. Alkyl sulfates such as ammonium lauryl sulfate, ethanolamine lauryl sulfate, sodium lauryl sulfate, and triethanolamine lauryl sulfate;

  Polyoxyethylene (2EO) lauryl ether sulfate triethanolamine (where EO means ethylene oxide, the value before EO indicates the number of moles of ethylene oxide added), polyoxyethylene (3EO) alkyl (carbon number 11 -15 or a mixture of two or more thereof) polyoxyethylene alkyl sulfate such as sodium ether sulfate. Alkylbenzenesulfonates such as sodium laurylbenzenesulfonate and triethanolamine laurylbenzenesulfonate. Polyoxyethylene alkyl ether acetates such as sodium polyoxyethylene (3EO) tridecyl ether acetate. Coconut oil fatty acid sarcosine sodium, lauroyl sarcosine triethanolamine, sodium lauroylmethyl-L-glutamate, coconut oil fatty acid-sodium L-glutamate, coconut oil fatty acid-L-glutamate triethanolamine, coconut oil fatty acid methyltaurine sodium, lauroylmethyltaurine N-acyl amino acid salt such as sodium, sodium ether sulfate alkane sulfonate, hydrogenated coconut oil fatty acid sodium glyceryl sulfate, hydrogenated coconut oil fatty acid sodium glycerine sulfate, disodium undecinoylamidoethylsulfosuccinate, sodium octylphenoxy dientoxyethyl sulfonate , Disodium aminosulfosuccinate, dioctyl sodium sulfosuccinate, dioctyl sodium sulfosuccinate Disodium lauryl sulfosuccinate, polyoxyethylene alkyl (carbon chain 12-15) ether phosphate (8-10 EO), polyoxyethylene oleyl ether sodium phosphate, polyoxyethylene cetyl ether sodium phosphate, polyoxyethylene sulfosuccinate lauryl Anionic surfactants such as disodium, sodium polyoxyethylene lauryl ether phosphate, sodium lauryl sulfoacetate, sodium tetradecene sulfonate. Stearyldimethylammonium chloride, di (polyoxyethylene) oleylmethylammonium chloride, stearyldimethylbenzylammonium chloride, stearyltrimethylammonium chloride, tri (polyoxyethylene) stearylammonium chloride, polyoxypropylenemethyldiethylammonium chloride, myristyldimethylbenzylammonium chloride Cationic surfactants such as lauryltrimethylammonium chloride. 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, sodium undecylhydroxyethylimidazolinium betaine, undecyl-N-hydroxyethyl-N-carboxymethylimidazolinium betaine, stearyl dihydroxyethyl betaine, palm Oil fatty acid amidopropyl betaine, coconut oil alkyl-N-carboxyethyl-N-hydroxyethyl imidazolinium betaine sodium, coconut oil alkyl-N-carboxymethoxyethyl-N-carboxymethylimidazolinium disodium lauryl sulfate, N-coconut Amphoteric surfactants such as oil fatty acid acyl-N-arginine ethyl-DL-pyrrolidone carboxylate. Polyoxyethylene alkyl (carbon number 12-14) ether (7EO), polyoxyethylene octyl phenyl ether, polyoxyethylene oleyl ether, polyoxyethylene oleic acid glycerin, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxy Ethylene cetyl stearyl diether, polyoxyethylene sorbitol lanolin (40EO), polyoxyethylene nonylphenyl ether, polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene decyl tetradecyl ether, polyoxyethylene lanolin, polyoxy Nonionic surfactants such as ethylene lanolin alcohol and polyoxypropylene stearyl ether. Isostearic acid diethanolamide, undecylenic acid monoethanolamide, oleic acid diethanolamide, beef tallow fatty acid monoethanolamide, hardened tallow fatty acid diethanolamide, stearic acid diethanolamide, stearic acid diethylaminoethylamide, stearic acid monoethanolamide, myristic acid diethanolamide, Thickeners such as coconut oil fatty acid diethanolamide, coconut oil fatty acid ethanolamide, lauric acid isopropanolamide, lauric acid ethanolamide, lauric acid diethanolamide, and lanolin fatty acid diethanolamide. Silicon oils such as linear or cyclic methylpolysiloxane, methylphenylpolysiloxane, dimethylpolysiloxane polyethylene glycol copolymer, dimethylpolysiloxane polypropylene copolymer, amino-modified silicone oil, and quaternary ammonium-modified silicone oil.

  Beer extract, pH adjuster, colorant, fragrance, stabilizer, refreshing agent, blood flow promoter, keratolytic agent, astringent, wound treatment agent, foam enhancer, oral agent, deodorant / deodorant, anti-deodorant Allergic agents, cell activators, etc. Inactive carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, preservatives, buffering agents and the like.

  The Shiranui Chrysanthemum extract according to the present invention, or an anti-skin aging agent, collagenase inhibitor, elastase inhibitor, antioxidant, anti-glycation agent, collagen production promoter, or elastase production promoter containing the same is added to a medicament. Can also be used. That is, the present invention relates to the Shiranui Chrysanthemum extract according to the present invention, or an anti-skin aging agent, collagenase inhibitor, elastase inhibitor, antioxidant, anti-glycation agent, collagen production promoter, or elastase production promoter containing the same. A medicament comprising the same is also provided. Such medicaments according to the present invention can exert their respective anti-skin aging effects by being administered to patients having skin troubles.

  The medicament according to the present invention includes pharmaceuticals and quasi drugs. The medicament according to the present invention may be an oral drug or a parenteral drug, but is preferably an external drug, and more preferably an external drug. The medicament according to the present invention may be in any dosage form, for example, ointments, patches, poultices, liniments, lotions, creams, extracts, fluid extracts, tinctures, elixirs, syrups. Agents, limonade agents, fragrances, liquids, suspending agents, emulsions, medicated baths, medicated shampoos, aerosols, powders, granules, tablets, capsules and the like.

  In addition to the Shiranui Chrysanthemum extract, any other component that can be blended with the medicament can be blended with the medicament according to the present invention. Other ingredients include inert carriers (solid or liquid carriers) used in medicine, excipients, surfactants, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspension agents, and coatings. Agents, colorants, flavoring agents, preservatives, buffering agents, and other active ingredients (for example, other anti-skin aging agents, moisturizers, whitening agents, sunscreen agents, astringents, etc.) It is not limited to this, The thing suitable for the use and form of a medicine can be arbitrarily selected and used. Some of the other ingredients that can be incorporated into the medicament are common with the ingredients listed above for cosmetics. The medicament according to the present invention can be produced by a conventional method.

  For example, specific examples of excipients include starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, and inorganic salts.

  Specific examples of the disintegrant include crystalline cellulose, methylcellulose, low-substituted hydroxypropylcellulose, carmellose (carboxymethylcellulose), carmellose calcium, carmellose sodium, croscarmellose sodium, wheat starch, rice starch, corn starch, potato starch , Partially pregelatinized starch, hydroxypropyl starch, sodium carboxymethyl starch, tragacanth and the like.

  Specific examples of the binder include crystalline cellulose, crystalline cellulose / carmellose sodium, methylcellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carmellose sodium , Ethylcellulose, carboxymethylethylcellulose, hydroxyethylcellulose, wheat starch, rice starch, corn starch, potato starch, dextrin, pregelatinized starch, partially pregelatinized starch, hydroxypropyl starch, pullulan, polyvinylpyrrolidone, aminoalkyl methacrylate copolymer E, aminoalkyl METAKU Rate copolymer RS, methacrylic acid copolymer L, methacrylic acid copolymer, polyvinyl acetal diethylamino acetate, polyvinyl alcohol, gum arabic, gum arabic powder, agar, gelatin, white shellac, tragacanth, purified sucrose, macrogol and the like.

  Specific examples of lubricants include wheat starch, rice starch, corn starch, stearic acid, calcium stearate, magnesium stearate, hydrous silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, dry aluminum hydroxide gel, talc, Examples thereof include magnesium aluminate metasilicate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, sucrose fatty acid ester, waxes, hydrogenated vegetable oil, polyethylene glycol and the like.

  Specific examples of surfactants include soybean lecithin, sucrose fatty acid ester, polyoxyl stearate, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, sorbitan sesquioleate, sorbitan trioleate, sorbitan monostearate Sorbitan monopalmitate, sorbitan monolaurate, polysorbate, glyceryl monostearate, sodium lauryl sulfate, lauromacrogol and the like.

  Anti-skin aging agent, collagenase inhibitor, elastase inhibitor, antioxidant, anti-glycation agent, collagen production promoter, or elastase production promoter according to the present invention (in the present specification, these may be collectively referred to as “agents”) The cosmetics or medicaments according to the present invention can be administered (applied) to any mammal (subject) including humans, domestic animals, pets, experimental (test) animals, etc. To subjects with high risk of promoting skin aging such as highly exposed to ultraviolet rays, subjects with accelerated skin aging, subjects with high need for prevention or improvement of skin aging, etc. It is particularly useful for administration. The present invention relates to a method for enhancing the anti-skin aging effect by administering (preferably applying to the skin) an agent according to the present invention, or a cosmetic or pharmaceutical according to the present invention to a subject, and thereby preventing skin aging. Or an improvement method is also provided. The present invention also provides a collagenase inhibitory action, an elastase inhibitory action, an antioxidant action, an anti-glycation by administering (preferably applying to the skin) the agent according to the present invention, or the cosmetic or pharmaceutical composition according to the present invention to a subject. Also provided are methods for enhancing the action, the collagen producing action, or the elastase producing action.

  The dose (applied amount) of the agent according to the present invention or the cosmetic or pharmaceutical agent according to the present invention varies depending on the species of the subject, age, body weight, route of administration, dosage form, use, frequency of administration, etc. Can be changed in a wide range at the discretion of Specifically, the dosage is not particularly limited, but is, for example, 0.001 g / time to 1 g / time in terms of dry weight of the Shiranui Chrysanthemum extract according to the present invention which is an active ingredient. be able to. Although the agent which concerns on this invention, or the cosmetics or pharmaceutical which concerns on this invention is not limited, For example, it is also preferable to administer repeatedly at intervals of 6 to 24 hours.

  Hereinafter, the present invention will be described more specifically with reference to examples. However, the technical scope of the present invention is not limited to these examples.

  EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited by this Example.

Example 1
<Preparation of Shiranui Chrysanthemum above ground extract>
(1) Preparation of alcohol extract-1
10 kg of the above-ground part of Chrysanthemum indicam × Erigeron annuus (including flowers, leaves, and stems, not including roots) was air-dried for about two weeks immediately after harvesting in a well-ventilated shade. After cutting, it was dried at 90 ° C. for 180 minutes and pulverized. 10 g of the obtained pulverized product was immersed in 100 mL of a 20% aqueous ethanol solution and extracted at 60 ° C. for 24 hours. The solution after extraction was centrifuged at 10,000 g for 10 minutes, and the precipitate in the solution was removed by filtration to obtain a brown and clear Shiranui Chrysanthemum extract.

(2) Preparation of freeze-dried powder The Shiranui Chrysanthemum extract obtained in (1) “Preparation of alcohol extract-1” was concentrated by an evaporator, and then freeze-dried in vacuo to obtain a freeze-dried powder.

(3) Preparation of water extract 10 g of crushed material obtained by drying and pulverizing the above-ground part of Shiranui Chrysanthemum (including flowers, leaves and stems, not including roots) as described in (1) above with 100 mL of water And was extracted at 60 ° C. for 24 hours. The solution after extraction was centrifuged at 10,000 g for 10 minutes, and the precipitate in the solution was removed by filtration to obtain a brown and clear Shiranui Chrysanthemum extract.

(4) Preparation of alcohol extract-2
As above (1), 10 g of the pulverized product obtained by drying and pulverizing the above-ground part of Shiranui Chrysanthemum (including flowers, leaves, and stems, not including roots) was immersed in 100 mL of absolute ethanol at 60 ° C. Extraction was performed over 24 hours. The solution after extraction was centrifuged at 10,000 g for 10 minutes, and the precipitate in the solution was removed by filtration to obtain a light brown and clear Shiranui Chrysanthemum extract.

(5) Preparation of alcohol extract-3
100 g of 20% 1,3-butylene glycol aqueous solution of 10 g of the pulverized product obtained by drying and pulverizing the above-ground part of Shiranui Chrysanthemum (including flowers, leaves and stems, not including roots) as described in (1) above And extracted for 2 weeks at room temperature. The solution after extraction was centrifuged at 10,000 g for 10 minutes, and the precipitate in the solution was removed by filtration to obtain a light brown and clear Shiranui Chrysanthemum extract.

(6) Preparation of alcohol extract-4
As above (1), 10 g of the pulverized product obtained by drying and pulverizing the above-ground part of Shiranui Chrysanthemum (including flowers, leaves and stems, not including roots) is immersed in 100 mL of 1,3-butylene glycol. The extraction was performed at 60 ° C. for 24 hours. The solution after extraction was centrifuged at 10,000 g for 10 minutes, and the precipitate in the solution was removed by filtration to obtain a light brown and clear Shiranui Chrysanthemum extract.

(Example 2)
<Preparation of Shiranui Chrysanthemum whole plant extract>
(1) Preparation of alcohol extract-5
10 kg of Shiryu Chrysanthemum (Chrysanthemum indicam × Erigeron annuus) whole plant (including flowers, leaves, stems and roots) was immediately air-dried for about 2 weeks in a well-ventilated shade after harvesting. After cutting, it was dried at 90 ° C. for 180 minutes and pulverized. 10 g of the obtained pulverized product was immersed in 100 mL of a 20% aqueous ethanol solution and extracted at 60 ° C. for 24 hours. The solution after extraction was centrifuged at 10,000 g for 10 minutes, and the precipitate in the solution was removed by filtration to obtain a brown and clear Shiranui Chrysanthemum extract.

(2) Preparation of freeze-dried powder The Shiranui Chrysanthemum extract obtained in (1) “Preparation of alcohol extract-5” was concentrated by an evaporator and then freeze-dried in vacuo to obtain a freeze-dried powder.

(3) Preparation of water extract As described in (1) above, 10 g of the crushed material obtained by drying and pulverizing 10 kg of the whole Shiranui chrysanthemum (including flowers, leaves, stems and roots) is immersed in 100 mL of water. The extraction was performed at 60 ° C. for 24 hours. The solution after extraction was centrifuged at 10,000 g for 10 minutes, and the precipitate in the solution was removed by filtration to obtain a brown and clear Shiranui Chrysanthemum extract.

(Example 3)
<Collagenase inhibition test>
500 μg / mL (500 ppm) and 100 μg of the lyophilized powder derived from the above-mentioned Shiranui Chrysanthemum prepared in Example 1 (2) and the lyophilized powder derived from the entire Shiranui Chrysanthemum plant obtained in Example 2 (2), respectively. A test solution was prepared by suspending in water at a concentration of 50 μg / mL (50 ppm).

  About the prepared test liquid, collagenase inhibitory action was evaluated using collageno kit CLN-100 (collagen technology workshop limited company, Kiyose-shi, Tokyo). Specifically, 50 μL of the test solution and 200 μL of human skin fibroblast-derived collagenase solution (0.1 unit / mL) are added to 200 μL of the substrate collagen solution (fluorescence-labeled collagen 0.1% / 0.01 M acetic acid), After reaction at 35 ° C. for 2 hours, the enzyme reaction stop solution (o-phenanthroline) is added to stop the enzyme reaction, and after cooling, 70% ethanol is added and stirred for 20 seconds, and the supernatant is recovered by centrifugation. As a result, an ethanol extract containing a collagen degradation product was obtained. The obtained extract was measured for fluorescence intensity (Ex = 495 nm, Em = 520 nm) using a fluorescence spectrophotometer. The higher the measured fluorescence intensity, the higher the collagenase activity. As a control, a buffer solution was added instead of the test solution containing the Shiranui Chrysanthemum extract, and the same reaction and measurement were performed. The collagenase activity inhibition rate of each test solution was calculated as follows in comparison with the measured value of the control (no addition of Shiranui Chrysanthemum extract).

  Collagenase activity inhibition rate (%) = (fluorescence value of control−fluorescence value upon addition of test solution) / fluorescence value of control × 100

  The results are shown in FIG. As shown in FIG. 2, high collagenase inhibitory activity was observed in any of the test solutions of 500 μg / mL, 100 μg / mL, and 50 μg / mL. Moreover, the extract derived from the Shiranui Chrysanthemum above ground and the extract derived from the entire Shiranui Chrysanthemum all showed high collagenase inhibitory activity, but the extract derived from the Shiranui Chrysanthemum above ground showed higher collagenase inhibitory activity. Collagenase inhibition level increased depending on the concentration of Shiranui Chrysanthemum extract.

  Thus, the Shiranui Chrysanthemum extract strongly inhibited the activity of collagenase, which is one of matrix metalloproteases, and thus was shown to be effective in preventing skin aging.

Example 4
<Elastase inhibition test>
The ignorant fire chrysanthemum extract lyophilized powders prepared in Example 1 (2) and Example 2 (2) were 0.2 M Tris at concentrations of 500 μg / mL, 200 μg / mL, 100 μg / mL, and 50 μg / mL, respectively. A test solution was prepared by suspending in hydrochloric acid buffer (pH 8.5, containing 1% BSA, 1M NaCl).

  Substrate solution 200 μL of substrate Suc- (OMe)-(L-alanyl) 2-Pro-Val-p-MCA adjusted to 20 μM with 0.2 M Tris-HCl buffer (pH 8.5, 1% BSA, containing 1 M NaCl) Then, 100 μL of the test solution of each concentration was mixed, 100 μL of human neutrophil-derived elastase solution prepared to 0.2 units / mL was added to the mixture, and the mixture was reacted at 37 ° C. for 1 hour. After the reaction, fluorescence intensity (Ex = 355 nm, Em = 460 nm) was measured. Higher measured fluorescence intensity means higher elastase activity. As a control, a buffer solution was added instead of the test solution containing the Shiranui Chrysanthemum extract, and the same reaction and measurement were performed. The elastase activity inhibition rate of each test solution was calculated as follows in comparison with the measured value of the control (no addition of Shiranui Chrysanthemum extract).

  Elastase activity inhibition rate (%) = (fluorescence value of control−fluorescence value upon addition of test solution) / fluorescence value of control × 100

  The results are shown in FIG. As shown in FIG. 3, the Shiranui Chrysanthemum extract highly inhibited elastase activity in a concentration-dependent manner. The extract derived from the Shiranui Chrysanthemum above ground and the extract derived from the whole Shiranui Chrysanthemum all showed high elastase inhibitory activity, but the extract derived from the Shiranui Chrysanthemum above ground showed higher elastase inhibitory activity.

  Thus, the Shiranui Chrysanthemum extract strongly inhibited the activity of elastase, indicating that it is also effective in preventing skin aging.

(Example 5)
<Evaluation of antioxidant activity>
Antioxidant effect of Shiranui Chrysanthemum extract was evaluated by DPPH radical scavenging method. The DPPH radical elimination method is a method in which DPPH (1,1-diphenyl-2-picryl-hydrazyl), which is a stable radical that absorbs in the visible region and does not exhibit absorption when reduced, is reacted with an antioxidant. This is a method for evaluating the antioxidant ability of an antioxidant substance based on determining the amount of DPPH that has not been reduced by the antioxidant substance by measuring absorbance.

  First, the ignorant fire chrysanthemum extract lyophilized powders prepared in Example 1 (2) and Example 2 (2) were each mixed with 50% aqueous ethanol solution to prepare 100 ppm test solution. Dispense 0.9 mL of a reaction indicator (800 μM 1,1-diphenyl-2-picryl-hydrazyl 12 mL, 400 mM 2-morpholinoethanesulfonic acid buffer 12 mL, 50% ethanol aqueous solution 24 mL) into a test tube, and add 50% ethanol aqueous solution. added. The addition amount of the 50% ethanol aqueous solution was determined as (300-a) μL with respect to the addition amount a μL of the test solution. a = 0, 30, 60, 120, 180, 240 μL. The test solution a μL was added, mixed with a vortex mixer, and the absorbance at 520 nm was measured 20 minutes after the addition of the test solution. As a control, 50% ethanol was added instead of the test solution containing the Shiranui Chrysanthemum extract, and the same reaction and measurement were performed. As a comparative experiment, the same reaction and measurement were performed using tea extract lyophilized powder instead of Shiranui chrysanthemum extract lyophilized powder. The radical scavenging rate of each test solution was calculated as follows by comparing with the measured value of the control.

  Radical scavenging rate (%) = (fluorescence value of control−fluorescence value upon addition of test solution) / fluorescence value of control × 100

  The results are shown in FIG. As shown in FIG. 4, the Shiranui Chrysanthemum extract was found to have higher radical scavenging activity than the tea extract, which has known antioxidant activity. The radical scavenging level increased depending on the concentration of Shiranui Chrysanthemum extract. The extract derived from the Shiranui Chrysanthemum above ground and the extract derived from the whole Shiranui Chrysanthemum all showed high radical scavenging activity, but the extract derived from the Shiranui Chrysanthemum above ground showed higher radical scavenging activity. From this, it was shown that the Shiranui Chrysanthemum extract has a high antioxidant effect. The Shiranui Chrysanthemum extract was also shown to be effective in preventing aging in terms of this antioxidant effect.

(Example 6)
<Evaluation of anti-glycation effect>
The ignorant fire chrysanthemum extract lyophilized powders prepared in Example 1 (2) and Example 2 (2) were dissolved in 8% ethanol to 4000 μg / mL, and then 500 μg / mL, 200 μg / mL, and 100 μg / mL, respectively. A test solution was prepared by suspending in demineralized water at a concentration of 50 mL / mL.

When 580 μL of 250 mM phosphate buffer (pH 7.4) was added to the light-shielding microtube, 20 μL of the test solution was added. Next, 200 μL of 2.5 M glucose aqueous solution was added, and 200 μL of BSA solution (10 mg / mL bovine serum albumin) prepared with a phosphate buffer was further added. The prepared sample solution was stirred and heated at 60 ° C. for 18 hours, and then the microtube was immersed in an ice bath to lower the temperature. After adding 100 μL of 100% (w / v) trichloroacetic acid and stirring, it was cooled at 4 ° C. for 15 minutes. Next, the supernatant is removed by centrifugation (11000 rpm, 4 ° C., 10 minutes), and alkaline PBS (137 mM NaCl, 8.1 mM Na ₂ HPO ₄ , 2.68 mM KCl, 1.47 mM KH ₂ PO ₄ ; 0.25 N) (Adjusted to pH 10 with NaOH) 1000 μL was added and stirred to dissolve the precipitate, and the fluorescence intensity (Ex = 355 nm, Em = 460 nm) was measured. The measured value of the fluorescence intensity indicates the amount of AGEs generated by the saccharification reaction between BSA and glucose. The same reaction and measurement were performed by adding demineralized water instead of the glucose aqueous solution as a blank. Further, as a control, demineralized water was added instead of the test liquid containing the Shiranui Chrysanthemum extract, and the same reaction and measurement were performed. The AGE generation inhibition rate of each test solution was calculated as follows.

AGE generation inhibition rate (%) = 100 − [(A−B) / (C−D)] × 100
A: Measured value when adding test solution B: Measured value of blank when adding test solution C: Measured value of control D: Measured value of blank in control

  The results are shown in FIG. As shown in FIG. 5, the Shiranui Chrysanthemum extract suppressed AGEs production to a high level, that is, showed high anti-glycation activity. The anti-glycation activity increased depending on the concentration of Shiranui Chrysanthemum extract. The extract derived from the Shiranui Chrysanthemum above ground and the extract derived from the whole Shiranui Chrysanthemum all showed high antiglycation activity, but the extract derived from the Shiranui Chrysanthemum above ground showed higher antiglycation activity. The Shiranui Chrysanthemum extract has been shown to be effective in preventing aging in terms of anti-glycation action.

(Example 7)
<Evaluation of collagen production promoting action>
Human fetal lung fibroblast WI-38 cells capable of collagen production suspended in DMEM medium supplemented with 10% FBS (fetal bovine serum) were cultured for 48 hours until they became confluent. The medium was discarded, and the cells washed with PBS three times were subjected to 500 μg / mL, 200 μg / mL, 100 μg / mL of the ignorant chrysanthemum extract lyophilized powder prepared in Example 1 (2) and Example 2 (2), DMEM medium (without FBS) added to 50 μg / mL was added and cultured for 48 hours. After the culture, the amount of collagen secreted into the medium was measured using a TAKARA Procollagen type IC-Peptide (PIP) EIA Kit, which is a collagen measurement kit. As a control, culturing and measurement were performed in the same manner except that the Shiranui Chrysanthemum extract lyophilized powder was not added to the FMEM-free DMEM medium. The collagen production promotion rate was calculated as a relative value as follows in comparison with the control (100%).

  Collagen production promotion rate (%) = collagen amount when adding Shiranui chrysanthemum extract / collagen amount for control × 100

  The results are shown in FIG. From FIG. 6, it was shown that the Shiranui Chrysanthemum extract has a high collagen production promoting effect. Collagen production promotion rate increased depending on the concentration of Shiranui Chrysanthemum extract. The extract derived from the Shiranui Chrysanthemum above ground and the extract derived from the whole Shiranui Chrysanthemum all showed higher collagen production promoting action, but the extract derived from the Shiranui Chrysanthemum above ground showed higher collagen production promoting action. Such a high collagen production promoting action indicates that the Shiranui Chrysanthemum extract is effective in preventing skin aging and improving skin elasticity and flexibility.

(Example 8)
<Evaluation of elastin production promoting action>
30,000 human skin fibroblasts (NB1RGB cells) were seeded per well in a 24-well plate containing 10% FBS (fetal bovine serum) -added DMEM medium, and cultured for 3 days in a 5 vol% CO ₂ environment. After culture, FBS added with the freeze-dried powder of Shiranui Chrysanthemum extract prepared in Example 1 (2) and Example 2 (2) to 500 μg / mL, 200 μg / mL, 100 μg / mL, and 50 μg / mL The medium was replaced with a DMEM medium containing no further culture. Four days later, the medium was collected, and the elastin concentration in the medium was measured using an elastin measurement kit, Fastin Elastin Assay Kit (Biocolor Ltd.). In addition, the number of cells in each well was counted, and the amount of elastin per unit cell number in each well was calculated. As a control, culturing and measurement were performed in the same manner except that the Shiranui Chrysanthemum extract lyophilized powder was not added to the FMEM-free DMEM medium. The elastin production promotion rate was calculated as a relative value as follows in comparison with the control (100%).

  Elastin production promotion rate (%) = Elastin amount per unit cell number when adding Shiranui Chrysanthemum extract / Elastin amount per unit cell number of control × 100

  The results are shown in FIG. From FIG. 7, it was shown that the Shiranui Chrysanthemum extract has a high elastin production promoting action. The elastin production promotion rate increased depending on the concentration of the Shiranui Chrysanthemum extract. The extract derived from the Shiranui Chrysanthemum above ground and the extract derived from the whole Shiranui Chrysanthemum all showed higher elastin production promoting action, but the extract derived from the Shiranui Chrysanthemum above ground showed higher elastin production promoting action. Such high elastin production promoting action indicates that the Shiranui Chrysanthemum extract is effective in preventing skin aging and improving skin elasticity and flexibility.

Example 9
<Manufacture of lotion>

  In accordance with the formulation of Table 1, components (1) to (10) were mixed and dissolved at 80 ° C. for each of the extract additive containing the Shiranui Chrysanthemum extract and the control product not containing the Shiranui Chrysanthemum extract. Then, it cooled to room temperature and prepared the lotion. All of the obtained lotions were clear and stable without causing cloudiness for 3 months under the conditions of 40 ° C. and relative humidity (PH) of 75%.

In addition, a sensory test was conducted by 10 professional panelists. The evaluation was performed in five grades for the following items (1) to (3).
(1) Moist skin 1. 1. It becomes bulky. Slightly soft 3. Normal 4. Slightly moist 5. Moisturizing (2) Skin smoothness 1. Rough Slightly rough 3. Normal 4. Slightly smooth Smooth (3) Skin stickiness 1. Sticky Slightly sticky 3. Normal 4. Slightly refreshing 5. Refreshing

  Table 2 shows the average scores of 10 panelists. As shown in Table 2, the extract additive containing the Shiranui Chrysanthemum extract showed better moisture retention and skin smoothness than the control product not containing the Shiranui Chrysanthemum extract.

(Example 10)
<Manufacture of shampoo agent>
According to the formulation of Table 3, components (1) to (8) were mixed and stirred at 70 ° C., and cooled to room temperature to prepare a shampoo agent.

  When the obtained shampoo was used to wash the hair, the hair feel was smooth and moisturized.

(Example 11)
<Manufacture of cream>

  In accordance with the formulation shown in Table 4, components (1) to (6) were mixed and stirred at 80 ° C., and then components (7) to (10) were separately mixed and stirred at 80 ° C., and then homogenized and stirred. After cooling to room temperature, a cream was prepared.

  The obtained cream (extract-added product) was not sticky during use, and the skin could be moistened.

  In addition, 10 professional panelists were targeted, and the obtained cream was tested for one month. After use, evaluation of the skin wrinkle and talmi improving effects was carried out by the following five grades.

1. 1. worsened Somewhat worse. No change Slightly improved Improved

  The average score of 10 panelists is shown in Table 5. As shown in Table 5, the extract-added product blended with the Shiranui Chrysanthemum extract showed a better wrinkle and tarmi improving effect than the control product without the Shiranui Chrysanthemum extract.

(Example 12)
<Manufacture of body gel>
According to the formulation shown in Table 6, components (1) to (8) were mixed and stirred and dissolved to prepare a body gel.

  The obtained body gel was not sticky during use, and the skin was moistened.

(Example 13)
<Manufacture of hair packs>
According to the formulation shown in Table 7, components (1) to (2) were mixed and stirred at 80 ° C., then components (3) to (13) were separately mixed and stirred at 80 ° C., and mixed and stirred at 80 ° C. Then, the components (14) and (15) were further added and mixed and stirred to prepare a hair pack agent.

  When the hair was treated with the obtained hair pack agent, the hair feel was smooth and moisturized.

(Example 14)
<Manufacture of shampoo agent>
According to the formulation shown in Table 8, components (1) to (8) were mixed and stirred at 70 ° C., and cooled to room temperature to prepare a shampoo agent.

  When the obtained shampoo was used to wash the hair, the hair feel was smooth and moisturized.

(Example 15)
<Manufacture of cream>
In accordance with the formulation shown in Table 9, components (1) to (6) were mixed and stirred at 80 ° C., then components (7) to (10) were separately mixed and stirred at 80 ° C., homogenized and stirred. After cooling to room temperature, a cream was prepared.
The obtained cream was not sticky during use, and the skin could be moistened.

(Example 16)
<Manufacture of body rinse>
A body rinse was prepared by a conventional method according to the formulation shown in Table 10. The obtained body rinse was able to moisturize the skin.

(Example 17)
<Manufacture of granular bath preparation>
According to the formulation shown in Table 11, the components (1) to (3) were mixed and stirred to prepare a granular bath preparation. The obtained granular bath preparation was able to moisturize the skin and was excellent in body temperature retention after use.

(Example 18)
<Manufacture of body gel>
According to the formulation shown in Table 12, components (1) to (8) were stirred and dissolved to prepare a body gel agent. The obtained body gel was not sticky during use, and the skin was moistened.

(Example 19)
<Manufacture of shampoo agent>
According to the formulation shown in Table 13, components (1) to (8) were mixed and stirred at 70 ° C., and cooled to room temperature to prepare a shampoo agent.

  When the obtained shampoo was used to wash the hair, the hair feel was smooth and moisturized.

(Example 20)
<Manufacture of body rinse>
According to the formulation shown in Table 14, body rinse was prepared by a conventional method. The obtained body rinse was able to moisturize the skin.

Claims (7)

A collagenase inhibitor containing an extract of Chrysanthemum indicam x Erigeron annuus as an active ingredient , wherein the Shiranui Chrysanthemum extract comprises 50% or less after drying and pulverizing the above-ground part or whole grass of Shiranui Chrysanthemum. A collagenase inhibitor obtained by immersing in an aqueous alcohol solution having a concentration and performing extraction at 50 to 70 ° C. for 10 to 48 hours . A collagen production promoter containing an extract of Chrysanthemum indicam x Erigeron annuus as an active ingredient , the Shiranui Chrysanthemum extract being 50% or less after drying and pulverizing the above-ground part or whole plant of Shiranui Chrysanthemum Collagen production promoter obtained by soaking in an aqueous alcohol solution having a concentration of 10 to 48 hours at 50 to 70 ° C. An elastin production promoter containing, as an active ingredient, an extract of Chrysanthemum indicam × Erigeron annuus , wherein the extract of Shiranui Chrysanthemum is dried and ground to 50% or less after drying and grinding An elastin production promoter obtained by immersion in an aqueous alcohol solution having a concentration of 10 to 48 hours at 50 to 70 ° C. The agent according to any one of claims 1 to 3, wherein the alcohol aqueous solution is an alcohol aqueous solution having a concentration of 10 to 50%. The agent of any one of Claims 1-4 which performs the said extraction at 60 degreeC. Cosmetics for collagenase inhibition, collagen production promotion, or elastin production promotion containing the agent of any one of Claims 1-5 . A medicament for inhibiting collagenase, for promoting collagen production, or for promoting elastin production, comprising the agent according to any one of claims 1 to 5 .

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