KR20170025352A - Composition for improving skin - Google Patents

Abstract

The present invention relates to a composition for improving skin. According to the present invention, the extract of Zanabi stalactisia mushroom extract promotes skin cell regeneration, promotes collagen synthesis of skin fibroblasts, exerts excellent effect of PPAR alpha, and improves skin brightness, thereby regenerating skin, improving wrinkles, improving elasticity, improving atopy And for the production of medicines, cosmetics or foods for improving skin texture. In addition, it promotes the proliferation of dermal stem cells and exhibits a stem cell-retaining effect, and thus can be used for the production of a cosmetic for promoting stem cell activity.

Description

[Composition for improving skin]

The present invention relates to a skin improving composition exhibiting skin regeneration, wrinkle improvement, elasticity improvement, atopy improvement, skin texture improvement, and stem cell activity promoting effect.

Collagen is a major substrate protein produced in fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical rigidity of skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, division of cells and differentiation Growth or wound healing) are known. Such collagen is reduced by aging and photo aging caused by ultraviolet irradiation, which is known to be closely related to the wrinkling of the skin. Also, in recent years, extensive research on skin aging has developed, and important functions of collagen in skin have been revealed.

Effective ingredients promoting collagen synthesis and exhibiting wrinkle-reducing effects are known. For example, retinoic acid, transforming growth factor (TGF) [non-patent document 1], animal placenta-derived protein [Patent document 1], betulinic acid [Patent document 2], chlorella extract [ Patent Documents 3 and 4] are known as collagen synthesis promoting substances. However, the above-mentioned effective ingredients are limited in the use amount due to safety problems such as irritation and redness when applied to the skin, or have insufficient effect, so that the effect of improving the skin function by promoting the collagen synthesis of the skin can not be expected.

In addition, the epidermis located at the outermost part of the skin protects against various external physical, chemical and mechanical stimuli and protects against excessive divergence of body water through the skin. This protective function is possible by normally forming and maintaining the stratum corneum composed of keratinocytes. The keratinocyte is a cell formed by a stepwise change in morphology and function while a basal cell that continuously proliferates in the stratum basale moves to the stratum corneum, Forming cells are removed from the skin and the new keratinocytes from the epidermis's bottom layer repeat the process of epidermis differentiation or keratinization replacing its function. In this keratinization process, keratinocytes produce intercellular lipids such as natural moisturizing factors (NMF) and ceramides, cholesterol, and fatty acids, which act as barrier layers to the outside, As shown in Fig.

In addition, skin dryness, which is considered to be one of the major diseases of modern society, is one of the symptoms caused by skin barrier function abnormality. Recently, environmental pollution, increase in dry environment such as apartments and high rise building, increase in social stress, Of excessive bathing, skin aging, and the like, and the cases of severe symptoms and the need for treatment are also increasing steadily.

Atopic dermatitis, which is present in 10% of children in recent years, is also known to be a cause of dry skin syndrome, and more fundamentally, abnormal skin barrier function. In order to treat such atopic dermatitis, studies have been carried out in order to supply water from the outside or minimize water loss from the body by focusing on proper moisture retention in the skin in the past. Actually, ceramide or derivatives thereof have been developed and are widely used in the pharmaceutical or cosmetic field.

However, the use of such a moisturizing agent is not only a fundamental treatment but a temporary symptom relief, and thus has not shown sufficient effect for treatment of dry skin and skin barrier function including atopic dermatitis. Therefore, it is urgent to develop a substance that can restore the damaged skin barrier fundamentally.

Recently, it has been known that PPAR alpha (peroxisome proliferator activated receptor-alpha) present in keratinocyte cells is activated by binding to its ligand, thereby promoting the differentiation of keratinocytes and reconstructing damaged skin barrier. In the case of applying Clofibrate (non-patent document 2) or WY 14643 (non-patent document 3), which is an agonist of known PPAR alpha, to the skin of which skin barrier is damaged, differentiation of keratinocytes is promoted And recovery of the skin barrier is promoted.

In addition, the skin texture, which is the shape of the skin surface, is characterized by a three-dimensional microstructure formed by fine lines and is significantly different according to age and site. The skin texture is divided into primary (about 20-100 μm), secondary (about 5-40 μm), and tertiary (about 0.5 μm) lines depending on the depth of the line. And has a distinctive polygonal shape and star formation due to the contact of the lines [Non-Patent Document 4].

However, as the age increases or the skin becomes damaged, the network structure of the dense fine lines collapses and fine lines (secondary, tertiary, etc.) disappear and the primary lines become deeper and wrinkles are known to be produced Literature 5, 6]. In other words, wrinkles, a typical sign of skin aging, are accumulations of minute changes that have already occurred over a long period of time.

Embryologically, all components of human skin are known to originate from ectoderm or mesodermal lobe. Epidermis, hair follicles, sebaceous glands and glands are originated from ectoderm, and melanocytes, nerves and special sensory receptors are derived from neuroepithelial cells. According to the developmental stage, the embryonic stem cells are repeatedly differentiated and become cells with the characteristics of each tissue function. After the embryo, a certain number of stem cells remain in the tissue. . The first is in the hair follicle. It is known to play an important role in the regeneration of the epidermis into cells before cell differentiation occurs, and plays an important role in hair regeneration and growth. The second is the basal layer of the epidermis. The stem cells found here play an important role in maintaining skin health by administering not only the epidermis but also the fibroblasts of the dermal layer. The stem cells here are relatively large in quantity and easy to obtain, making them widely used in the study of skin stem cells. The skin is constantly renewed, and stem cells present in the epithelium of the skin, that is, epidermal stem cells of the skin, are involved in the repair of the epithelium after injury [Non-Patent Document 7]. The epithelial stem cells of the skin are also referred to as skin stem cells. When the skin stem cells are activated, it is possible to treat skin wounds such as trauma, promote wound healing, have. Integrin β1 and integrin α6 are used as indicators of dermal stem cells, and maintenance of skin stem cells necessary for epithelial morphogenesis and differentiation has been reported to be regulated by p63 protein.

Dermal stem cells play an important role in maintaining the health and physiological and biochemical homeostasis of the skin. Stem cells present in the skin are also abnormally functioned due to the effect of aging, and thus various problems arise as the homeostasis of the skin is broken. Therefore, it is possible to improve various phenomena of skin aging through the activation of stem cells [Non-Patent Document 8].

In addition, it is safe and effective in the living body, stable in the active ingredient, more effective than the existing skin regeneration, wrinkle improvement, elasticity enhancement, atopic improvement and skin texture improvement effect, skin regeneration, wrinkle improvement, elasticity improvement, atopy improvement And a component having skin-improving activity are strongly desired.

On the other hand, Elfvingia applanata Karst. Is a perennial wood rot fungus that grows year round on hardwood flesh or dead trees. The width of mushroom god is 10 ~ 50cm, and it is more than 30 ~ 40cm in thickness. It is shaped like horseshoe or bell in semicircular shape, low mountain shape. The surface is covered with pebbles and grayish white or grayish brown. The surface is covered with spores like cocoa powder and shows cocoa color. Flesh is chocolate colored, 1 ~ 5cm thick, and fur-like cork quality. The holes are multi-layered, and each layer has a thickness of 0.5 to 2 cm. It is yellowish white or white, and dark brown when touched. There is no sack, but a gland attaches to the host. In Korea, it is native to Yeonsan Peninsula National Park, Odaesan, Jirisan, and Baekdusan, and is distributed throughout the world.

It has long been used as a traditional or folk remedy for a variety of diseases in China, Japan, and Korea. It has been used for a long time as a medicinal herb, such as a combination of ercosine-based steroid compounds and triterpenoids, It has been reported that it contains polysaccharides such as D-glucan. In particular, it is known as a mushroom with high anticancer effect along with mushroom and cloud mushroom. Recent studies describe many biological activities including anticancer, hypertension, cytotoxicity, antibiotic, antimicrobial, and anti-inflammatory

As described above, various pharmacological effects of the manganese manganese have been reported, but the mechanism of the skin of manganese manganese manganese has not yet been known, and no studies have been conducted on it.

Japan Patent No. 8-231370 Japan Patent No. 8-208424 Japan Patent No. 9-40523 Japan Patent No. 10-36283

Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974 Feingold et al., J. Invest. Dermatol., 110, pp 368-375, 1998. Feingold et al., J. Invest. Dermatol., 115, pp 353-360, 2000. Journal of the European Academy of Dermatology and Venereology. 12: 103-114, 1999 The British journal of dermatology. 110: 129-138, 1984 Skin research and technology.5: 189-194, 1999 Epidermal Stem Cells of the Skin, Cedric Blanpain, Elaine Fuchs, Annual Review of Cell and Developmental Biology, November 2006, Vol. 22, Pages 339-373 Human skin stem cells and the aging process, Catherine Niemann, Stem Cell Aging and Regenerative Medicine, November 2008, Pages 986-997

Accordingly, the present inventors have found that the extract of Zanthoxylum pentaphyllum mushroom promotes the regeneration of skin stem cells, promotes regeneration of the skin, promotes collagen synthesis of fibroblasts of skin, improves wrinkles, promotes elasticity, exhibits excellent activity of PPAR alpha The present invention has been accomplished by confirming the effect of promoting stem cell activity by promoting the proliferation of the skin stem cells and exhibiting the stem cell maintaining effect in addition to the effect of improving the skin texture due to the improvement of the skin brightness.

Accordingly, it is an object of the present invention to provide a composition for improving skin regeneration, wrinkle improvement, elasticity improvement, atopic eczema, and skin texture, which comprises Aspergillus oryzae mushroom extract as an active ingredient.

Another object of the present invention is to provide a composition for stimulating stem cell activity, which comprises the extract of Aspergillus oryzae as an active ingredient.

As a means for solving the above problems, the present invention provides a composition for improving skin regeneration, wrinkle improvement, elasticity improvement, atopic eczema and skin texture, which comprises an extract of Aspergillus oryzae as an active ingredient for the manufacture of medicines, cosmetics or foods do.

As another means for solving the above-mentioned problems, the present invention provides a composition for stimulating stem cell activity, comprising as an active ingredient, an extract of Aspergillus oryzae for the production of cosmetic formulations.

According to the present invention, the extract of Manganese manganese mushroom according to the present invention promotes the proliferation of skin stem cells to promote skin regeneration, promotes collagen synthesis of fibroblasts of skin to improve wrinkles, improve elasticity, and exhibits excellent activity of PPAR alpha, And has an effect of improving the skin texture due to the improvement of the skin brightness, so that it can be used for the production of medicines, cosmetics or foods.

In addition, the extract of Manganese manganese mushroom promotes the proliferation of dermal stem cells and exhibits a stem cell-keeping effect, and thus can be used for the production of cosmetic formulations for stimulating stem cell activity.

Hereinafter, the configuration of the present invention will be described in detail.

To regenerate skin, improve wrinkles, improve elasticity, improve atopy, and improve skin texture, it is necessary to improve skin regeneration, wrinkle improvement, elasticity improvement, atopy improvement and skin texture improving activity at low concentration And is low in volatility so as to be able to stay for a sufficient time to exhibit skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement and skin texture improving effect, and the active ingredient is stable And is easy to be manufactured into medicines, cosmetics, food or the like, and is preferably safe to the skin. However, the components satisfying all of the above-mentioned characteristics among the known components are not common. For example, some skin regeneration, wrinkle improvement, elasticity enhancement, atopic improvement, and skin tone improving ingredients are excellent in skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement and skin tone improving activity even at low concentration in in vitro test, It is difficult to apply to real skin because of its ability to permeate and absorb. Other active ingredients have low hydrophilicity, making them difficult to formulate into medicines, cosmetics, and foods. In addition, some skin regeneration, wrinkle improvement, elasticity enhancement, atopic improvement, and skin tone improvement components may be decomposed or converted into other compounds when exposed to heat, light, or oxygen, There are also cases.

As can be seen in the following examples, the extract of Manganese manganese mushroom showed remarkably excellent proliferation promoting effect on the skin stem cell at low concentration, promoting collagen synthesis, PPAR alpha activity and skin brightness, It can be used as an active ingredient of medicines, cosmetics or food compositions for improving elasticity, improving atopy and improving skin texture.

Accordingly, the present invention provides a composition for improving skin regeneration, wrinkle improvement, elasticity improvement, atopic eczema, and skin texture, which comprises an extract of Aspergillus oryzae as an active ingredient.

In the present invention, Elfvingia applanata Karst. Underw) is a mushroom belonging to the genus Flora, and is horseshoe-like or bell-shaped from a low mountain.

The extract can be extracted by a method known in the art, and the method is not particularly limited. Alternatively, commercially available extracts can be used.

Preferably, the extract may be extracted from water and / or an organic solvent. The organic solvent may be a polar organic solvent, a nonpolar organic solvent or a mixture thereof. The polar organic solvent may be a lower alcohol having 1 to 5 carbon atoms, ethyl acetate or acetone, and the nonpolar organic solvent may be ether, chloroform, benzene, hexane or dichloromethane. For example, the lower alcohol having 1 to 5 carbon atoms may be methanol, ethanol, propanol, butanol or isopropanol.

In one embodiment of the present invention, the manganese extract may comprise a fraction obtained by fractionating a primary extract extracted using the above-described extraction solvent with an extraction solvent having a different polarity. For example, the extract of Chrysanthemum sativus can be a fraction obtained by extracting with an alcohol having 1 to 5 carbon atoms and then fractionating again with a solvent having a different polarity such as ether, benzene, hexane or the like. Two or more kinds of solvents may be used for the fractionation, and the solvent extracts may be sequentially used or mixed according to the polarity of the solvent.

In the present invention, the extracted extract or the fraction obtained by performing the fractionation process may be filtered, concentrated or dried to remove the solvent, and the filtration, concentration, and drying may all be performed. Specifically, the filtration can be performed using a filter paper or a vacuum filter, and the concentration can be reduced by using a reduced pressure concentrator or the like, and the freeze-drying method can be carried out for drying.

The fractions obtained by performing the above-described extract or the fractionation process can be further purified by silica gel column chromatography, thin layer chromatography or high performance liquid chromatography Further purification can be achieved by purification using various chromatographic techniques.

The compositions of the present invention may be used for the manufacture of pharmaceutical formulations.

The pharmaceutical formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules.

In addition, the composition may further contain one or more active ingredients showing the same or similar functions. For example, it may contain known skin regeneration, wrinkle improvement, elasticity enhancement, atopic improvement, and skin tone improving ingredient. The skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement and skin texture improving effect of the composition of the present invention can be further enhanced if the composition further includes additional skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement and skin texture improvement. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the present invention, the composition is a skin regeneration component known in the art comprising retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract, antioxidant components known in the art, such as tocopherol, selenium , Vitamin C and phenolic compounds, whitening ingredients known in the art, substances inhibiting the activity of tyrosinase enzymes such as kojic acid and arbutin, hydroquinone, vitamin C (L- Ascorbic acid, derivatives thereof, and various plant extracts. The additional components may be contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content may be adjusted according to requirements such as skin safety, easiness in formulation of the extract of Aspergillus oryzae .

In addition, the composition of the present invention may further comprise a pharmaceutically acceptable carrier.

Pharmaceutically acceptable carriers may contain a variety of ingredients such as buffer, injectable sterile water, normal saline or phosphate buffered saline, sucrose, histidine, salts and polysorbates, and the like.

The composition of the present invention can be administered orally or parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, various forms of oral and parenteral administration at the time of clinical administration. In the case of formulation, a filler, , A binder, a wetting agent, a disintegrant, a surfactant, and the like.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like. These solid preparations can be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like can be prepared.

In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of liquid formulations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used.

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

In the present invention, the term 'skin regeneration effect' refers to the recovery of skin tissue against damage caused by external or internal causes of skin as the activity of skin stem cells is promoted. At this time, the damage caused by the external cause may include ultraviolet rays, external pollutants, wound or trauma, and the damage caused by the internal cause may be stress.

In the present invention, the term " wrinkle-reducing effect " refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating already-generated wrinkles.

In the present invention, the 'elasticity-enhancing effect' refers to an increase in elasticity to the skin, which suppresses or inhibits the loss of elasticity of the skin, or alleviates the already-reduced elasticity.

In the present invention, the term 'atopic improvement effect' refers to the effect of preventing and treating skin diseases such as atopy and dry skin, and is to inhibit, inhibit, or alleviate atopic symptoms.

In the present invention, the term " skin texture improving effect " refers to smoothing the skin surface, imparting gloss, and brightening the skin tone by inhibiting or inhibiting roughness of the skin surface due to aging, stress, .

In the present invention, the term " effective amount " refers to an amount of an extract capable of promoting regeneration of damaged skin, improving wrinkles, improving elasticity, improving skin dryness such as atopy, it means. When the composition of the present invention contains an effective amount of the extract of Mulberry japonica, it can provide desirable skin regeneration effect, wrinkle improvement effect, elasticity improving effect, atopic improvement effect and skin texture improving effect. The effective amount of the extract of Manganese manganic acid contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, the manner in which the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized in a pharmaceutical formulation, it may contain the extract of Zanthoxylum pentaphyllum mushroom at a higher concentration than that of a cosmetic product applied to skin on a daily basis. Accordingly, the daily dosage is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, based on the amount of the above-mentioned mugwort extract, 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 pharmaceutical formulations of the present invention may include external preparation for skin.

When the extract is used as an external preparation for skin, it may further contain a fatty substance, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, , Water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for skin And any other ingredients used in the skin sciences. The components can also be introduced in amounts commonly used in the field of dermatology.

When the extract is provided as an external preparation for skin, it may have a formulation such as, but not limited to, ointments, patches, gels, creams or sprays.

Further, the composition for skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement and skin texture improvement of the present invention can be used for the production of cosmetic formulations.

The cosmetic formulation may be in the form of a conventional emulsion formulation and a solubilized formulation. For example, creams, essences, cosmetic creams, sprays, gels, packs, sunscreens, make-up bases, liquids such as lotions such as lotion, facial lotion, body lotion, A powder, a cleansing lotion, a makeup removing agent such as a cleansing oil, a cleansing foam, a soap, a body wash, and the like.

In addition, the cosmetic composition may further comprise at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, Any of those commonly used in ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics ≪ RTI ID = 0.0 > cosmetic < / RTI >

The cosmetic formulations may contain a relatively high concentration of the extract of Manganese manganese (Manganese) mushroom extract in the case of a wash-off type cosmetic such as a make-up remover, a detergent, etc. in which the active ingredient remains on the skin in a short period of time. On the other hand, in the case of leave-on type cosmetics such as lotion, cream, essence, etc. in which the active ingredient remains on the skin for a long period of time, the lower concentration of the above- It may be included. In one embodiment of the present invention, but not limited thereto, the composition comprises 0.0001 wt.% To 10 wt.% (Preferably 0.0001 wt.% To 1 wt.%) . When the composition of the present invention contains less than 0.0001% by weight of the extract, the skin can not be expected to exhibit sufficient skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement and skin texture improvement, In this case, it is intended to prevent an allergic reaction such as an unwanted reaction or a skin safety problem.

The composition for skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement and skin texture improvement of the present invention can be used for the production of food formulations.

The food preparation refers to a food prepared by adding the above-mentioned Minami mushroom extract to a food material such as beverage, tea, spice, gum, confectionery, or the like, or by encapsulation, powdering, suspension or the like.

Since the food formulation can be ingested routinely, it is very useful because it can expect high skin regeneration, wrinkle improvement, elasticity improvement, atopy improvement and skin texture improvement effect.

When the extract is used as a food additive, the extract can be used as it is or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). Generally, the composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight, based on the raw material, when the food or beverage is produced. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range .

There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include dairy products including meats, sausages, breads, chocolates, candies, snacks, confections, pizza, ramen noodles, gums, ice cream, soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.

When the food is a beverage, various flavors or natural carbohydrates may be added as an additional ingredient such as a normal drink. The above-mentioned natural carbohydrates are sugar alcohols such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and 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 mL of the composition of the present invention.

In addition to the above, the food formulations may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, And the like. Other food formulations may 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 also provides a composition for stimulating stem cell activity comprising the extract of Aspergillus oryzae as an active ingredient.

The term 'stem cell' in the present invention is a cell capable of cell division by itself and capable of differentiating into a very specific type of specific cell type. The type of such stem cells is not particularly limited, and in one embodiment, the stem cells may be dermal stem cells. The term 'dermal stem cells' refers to stem cells that can be differentiated into cells constituting the skin (epidermis, dermis and subcutaneous fat layer). The cells that make up the skin include keratinocytes, melanocytes, and fibroblasts (mainly responsible for biosynthesis of collagen and elastin) present in the epidermis.

The kind of the skin stem cell is not particularly limited. The dermal stem cells used in the present invention can be used irrespective of where they originate from. For example, dermal stem cells may be obtained from a known source of dermal stem cells, e. G., From the basal layer of hair follicles or epidermis, and the animal to be harvested may be a mammal. In one embodiment, the mammal may include, but is not limited to, a human, a mouse, a rat, a guinea pig, a rabbit, a monkey, a pig, a horse, a cattle, a sheep, Preferably the mammal can be human. Such methods of obtaining dermal stem cells from dermal stem cell sources are well known in the art.

In the present invention, the term 'promoting effect on stem cell activity' refers to an effect of promoting stem cell proliferation and / or an effect of maintaining stem cell characteristics, which is a specific indicator molecule and a self-cleaving property of stem cells.

In addition, the compositions of the present invention can be used for the production of cosmetic formulations. These cosmetic formulations are the same as those described in the description of cosmetic formulations including Zanthoxylumbelliformes extracts.

Hereinafter, the present invention will be described in detail with reference to examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

Manufacturing example  One: Chinese cabbage mushrooms  Preparation of extract

The mushrooms were washed and pulverized, and then cooled in a 10-fold volume of ethanol for 5 days. Then, the extract solution was filtered and concentrated to obtain an extract. To this was added a mixed solution of purified water and ethanol to dissolve and then filtered to prepare a final extract.

Manufacturing example  2: Serum-free Under medium conditions Of dermal stem cells  culture

Human epidermal stem cells purchased from Cellntec were added to 48-well plates (6 × 10 ³ cells / well), supplemented with BPE (bovine pituitary extract) similar to fetal bovine serum And cultured for 24 hours at 5% CO ₂ and 37 ° C using CNT-57 medium (Cellntec). Thereafter, the culture medium was removed through a suction tube, and the medium was removed using a PBS solution (GibcoBRL). 5 g / ml of 5% g / m _{2 of} the extract was added to CNT-57 medium containing no BPE, And cultured at 37 ° C for 72 hours.

Experimental Example  One: CCK -8 Through evaluation method Dermal stem cells  Proliferation promoting effect

The skin stem cells cultured in Preparation Example 2 were evaluated for CCK-8 (Cell counting kit-8). The CCK-8 assay is an indirect method of measuring the density of living cells by measuring the absorbance of Formazan, a dehydrogenase in the intracellular electron transport system, produced by the decomposition of tetrazolium salt.

Cells were treated spectrophotometrically by treating CCK-8 solution (treated with 1/10 of the medium volume) at 37 ° C for 2 hours and then measuring the absorbance at 450 nm. From the measured absorbance value, the proliferation rate (%) of the skin stem cell of the extract of Staphylococcus aureus was determined in accordance with the following equation (1) with respect to the control group (CNT-57 medium supplemented with BPE) .

[Equation 1]

Growth rate (%) = (absorbance of sample-treated group / absorbance of control group) x 100

Promoting the proliferation of dermal stem cells Additive sample density Cell proliferation (%) versus control Mushroom extract 5 / / mL 132% Control group - 100%

As shown in Table 1, the skin stem cells in the culture medium treated with the extract of Chrysanthemum japonica showed excellent proliferation promoting effect.

Experimental Example  2: Of dermal stem cells  Stem cell ( stemness ) Confirm maintenance effect

The expression level of p63 was evaluated in order to confirm the stem cell maintenance effect of the dermal stem cells cultured in Production Example 2 above. p63 is an intracellular transcription factor and is well known as a maintenance marker for dermal stem cells. Cells were isolated and cDNA was synthesized. Then, real-PCR was performed with Taqman staining solution to measure the expression level of p63. The concentration of RNA in this experiment was normalized to S16 ribosomal RNA.

The experimental results are shown in Table 2 below. In Table 2 below, the numerical value of the increase in p63 is a multiple of the control group (CNT-57 medium supplemented with BPE).

Stem cell (stem cell) maintenance effect (number of repeats = 3) Additive sample density p63 Incremental multiple (times) Mushroom extract 5 / / mL 2.21 Control group - 1.0

As shown in Table 2, the medium conditions treated with the extract of Manganese manganic acid promote the p63 expression of the dermal stem cells, and thus the stem cell maintenance effect is excellent.

Example  1: Promoting collagen synthesis

The extracts of A. manganicum were added to the culture medium of human - derived fibroblasts to examine the effect of promoting collagen synthesis at the cellular level. The biocompatible collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immunoassay Kit).

And added to the culture medium of human fibroblasts (7 x 10 ⁴ cells / cm ² ) together with vitamin C and a control (no addition) so that the final concentration was 10 μg / mL and 20 μg / mL, respectively After culturing for 1 day, the culture broth was taken and the degree of collagen biosynthesis at each concentration was measured at 450 nm using a spectrophotometer with PICP EIA Kit. The collagen biosynthesis performance was calculated by the relative performance relative to the control group and the results are summarized in Table 3 below.

Promotion of collagen synthesis by concentration (number of repeats = 3) Additive sample Application concentration (/ / ml) Increase in collagen synthesis (%) compared to control Mushroom extract 10 [mu] g / ml 34.3% Mushroom extract 20 ug / ml 62.1% Vitamin C 50 ug / ml 33.9%

As shown in Table 3, the extract of Chrysanthemum japonica has excellent collagen synthesis ability against human-derived fibroblasts, and has a better collagen synthesis effect at a lower concentration than that of vitamin C, which is generally known to have collagen synthesis ability .

Example  2: PPAR  Verification of Alpha Activation Promotion Effect

In order to confirm the PPAR alpha activation promoting effect of the extract of A. manganica, the following experiment was carried out using the extract of A. manganica. C2C12 cells (ATCC CRL-1772), a mouse myoblast cell line, were subcultured in DMEM (Dulbecco's Modified Eagle's Medium) medium containing 10% fetal bovine serum. As the vector used herein,

1) A DNA fragment encoding GAL4-DBD (DNA Binding Domain), which is a transcription factor of yeast, and Ser ₁₆₇ to Tyr ₄₆₈ in human PPAR alpha LBD (Ligand Binding Domain), into a SV40 promoter of pZEO vector (Invitrogen) NM 005036);

2) a GAL4 response sequence inserted into a multiple restriction enzyme recognition site of a pGL3 vector (Promega) expressing luciferase and 3) a vector inserted into a transfection internal control with? -Galactosidase β-galactodisase) was used.

The cultured cells were plated on a 24-well plate at a concentration of 4 × 10 ⁴ and cultured for 12 hours. The three types of plasmid genes were transiently transfected using lipopectamine . After 8 hours, the extract was treated for 12 hours, washed with 1 x PBS, lysed with 1 x reporter lysis buffer, and luciferase assay kit (Promega) and The activity of luciferase was measured using? -galactosidase assay kit (Promega). That is, the PPAR alpha activity was measured as " luciferase activity / beta -galactose activity ".

Wy-14,643 (Calbiochem), the most potent ligand of PPAR alpha, was used as a positive control in this experiment, and DMSO 0.05% was used as a negative control.

According to the above experimental method, the activity of PPAR alpha was measured according to the concentration by treating C2C12 cells with the extract of A. manganiculata. The results are shown in Table 4 below. The values of PPAR alpha activity in Table 4 below represent percentages relative to negative control (0.05% DMSO).

Activity of PPAR alpha sample PPAR alpha activity (%) DMSO (0.05%) 100 Wy-14,643 (0.5 [mu] M) 355 Wy-14,643 (1 [mu] M) 921 Extract of Manganese mushroom (0.05%) 754 Chestnut mushroom extract (0.5%) 925

As shown in Table 4, compared with the positive control group, it was confirmed that the Chinese cabbage extract had a very strong PPAR alpha activity.

Example  3: For the improvement of the turn-over Efficacy

About the nutritional cream of the following formulation example 2, the effect of the improvement of the exfoliation of the skin in the healthy twenties to 50 women was tested as follows.

Twenty of 20 women aged 20 to 50 years were given a 1.5% solution of DHA (Dihydroxyacetone, Sigma Aldrich, USA) for 8 hours, followed by deposition. The preparation cream was applied twice daily to the test site. After 4 days of application, 8 days after application, 12 days after application, photographs were taken using instrument Chromameter CR-400 (Minolta, Japan) and skin lightness of DSLR and DSLR. The measured values were evaluated by three mean values excluding the maximum value and the minimum value. The higher the improvement in the skin brightness of the deposition site, the better the improvement of the exfoliation. The results are shown in Table 5 below.

Skin brightness improvement effect division Four days after application Eight days after application After 12 days of application Improvement rate (%) 1.64 4.23 11.67

As shown in Table 5, when the nutritional cream according to the present invention was used, it was found that the exfoliation of the skin was improved.

Formulation example  1: Manufacture of pharmaceutical preparations

1. Preparation of tablets

Chestnut mushroom extract 0.2mg

100 mg of corn starch

100 mg of milk

2 mg of magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

Formulation example  2: Manufacture of cosmetics

1. Manufacture of nutritional cream

As shown in the following composition, a nutritional cream containing an extract of Aspergillus oryzae as an active ingredient was prepared according to a conventional method.

0.2% by weight < tb >

Beta-1,3-glucan 5.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

≪ tb > < tb > < tb >

0.5% by weight of sorbitan sesquioleate

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

Caprylic / capric triglyceride 5.0 wt%

Glycerin 5.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

Formulation example  3: Preparation of external preparation for skin

1. Manufacture of ointment

As shown in the following composition, an ointment containing an extract of Aspergillus oryzae as an active ingredient was prepared according to a conventional method.

0.5% by weight < tb >

Beta-1,3-glucan 10.0 wt%

Wax 10.0 wt%

Polysorbate 60 5.0 wt%

≪ tb > < tb > < tb >

0.5% by weight of sorbitan sesquioleate

Vaseline 5.0 wt%

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

SHARE BUTTER 3.0 wt%

Caprylic / capric triglyceride 5.0 wt%

Glycerin 10.0 wt%

Propylene glycol 10.2 wt%

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

Claims (13)

A composition for regenerating skin comprising an extract of Aspergillus oryzae as an active ingredient.
The method according to claim 1,
A composition for regenerating skin, wherein the extract is obtained by extracting Manganese manganese mushroom with at least one selected from the group consisting of water and an organic solvent.
3. The method of claim 2,
The organic solvent may be a polar solvent containing a lower alcohol having 1 to 5 carbon atoms, ethyl acetate, or acetone; A nonpolar solvent comprising ether, chloroform, benzene, hexane or dichlorohexane; Or a mixed solvent thereof.
The method according to claim 1,
Wherein the composition is for the manufacture of a medicament for skin regeneration or wrinkle improvement, a cosmetic preparation or a food product.
A composition for improving skin wrinkles or elasticity, comprising an extract of Aspergillus oryzae as an active ingredient.
6. The method of claim 5,
Wherein the composition is for the manufacture of a medicament for enhancing skin elasticity, a cosmetic preparation or a food product.
A composition for improving atopy comprising an extract of Aspergillus oryzae as an active ingredient.
8. The method of claim 7,
Wherein the composition is for the manufacture of a medicament for the improvement of atopy, a cosmetic preparation or a food product.
A composition for improving skin texture comprising an extract of Aspergillus oryzae as an active ingredient.
10. The method of claim 9,
Wherein the composition is for the manufacture of a medicament for the improvement of skin texture, a cosmetic preparation or a food product.
A composition for promoting stem cell activity comprising an extract of Aspergillus oryzae as an active ingredient.
12. The method of claim 11,
Wherein the composition is for promoting stem cell proliferation or stem cell retention.
12. The method of claim 11,
Wherein the composition is for the production of a cosmetic for promoting stem cell activity.