KR20160128770A - Composition for improving skin - Google Patents

Abstract

The present invention relates to a composition for improving the skin. Anhydroicaritin in the present invention is used in producing pharmaceutical, cosmetic, food or external skin agent formulations for skin regeneration, wrinkle alleviation, elasticity enhancement, atopic alleviation, skin moisturizing and skin texture improvement through a collagen synthesis promoting effect, a filaggrin expression increasing effect and a skin brightness improving effect of skin fibroblast. In addition, the composition promotes the proliferation of dermal stem cells and exhibits a stemness maintaining effect, thereby being able to be used in producing a cosmetic formulation 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, atopic improvement, skin moisturizing, 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 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 possible to provide a skin regeneration, wrinkle improvement, elasticity enhancement which is more effective than a substance which is safe in the living body, stable in its effectiveness, and most of all has the effect of regenerating the existing skin, improving wrinkles, improving elasticity, improving atopy, , Atopic dermatitis, skin moisturization, and skin texture improving activity.

1. Japanese Patent Publication No. 8-231370 2. Japanese Patent Publication No. 8-208424 3. Japan Pyeonghwa 9-40523 4. Japan Patent No. 10-36283

1. Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974 2. Feingold et al., J. Invest. Dermatol., 110, pp 368-375, 1998. 3. Feingold et al., J. Invest. Dermatol., 115, pp 353-360, 2000. 4. Journal of the European Academy of Dermatology and Venereology. 12: 103-114, 1999 5. The British journal of dermatology. 110: 129-138, 1984, 6. Skin research and technology.5: 189-194, 1999 7. Epidermal Stem Cells of the Skin, Cedric Blanpain, Elaine Fuchs, Annual Review of Cell and Developmental Biology, November 2006, Vol. 22, Pages 339-373 8. Human skin stem cells and the aging process, Catherine Niemann, Stem Cell Aging and Regenerative Medicine, November 2008, Pages 986-997

Thus, the present inventors have found that Prim-O-glucosylcimifugin promotes collagen synthesis of fibroblasts of skin and promotes proliferation of skin stem cells, thereby promoting skin regeneration, improving wrinkles, improving elasticity, and exhibiting excellent activity of PPAR alpha It has the effect of improving atopy. It shows improvement effect of skin moisturization due to increase of filla green expression. It promotes the proliferation of skin stem cells as well as improvement of skin texture due to improvement of skin brightness, Confirming the effect of promoting activity, thereby completing the present invention.

Accordingly, an object of the present invention is to provide a composition for improving skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement, skin moisturizing and skin texture improvement comprising a compound represented by the following formula 1 as an active ingredient:

[Chemical Formula 1]

Another object of the present invention is to provide a composition for stimulating stem cell activity comprising a compound represented by the following formula (1) as an active ingredient:

[Chemical Formula 1]

As a means for solving the above problems, the present invention provides a method for improving the skin regeneration, wrinkle improvement, elasticity improvement, atopy improvement, and the like, which comprises, as an active ingredient, Skin moisturizing and skin texture improvement.

[Chemical Formula 1]

As another means for solving the above problems, the present invention provides a composition for promoting stem cell activity comprising, as an active ingredient, a compound represented by the following formula (1) for the production of a cosmetic formulation:

[Chemical Formula 1]

Prim-O-glucosylcimifugin according to the present invention promotes collagen synthesis of fibroblasts of the skin, promotes proliferation of skin stem cells, promotes skin regeneration, improves wrinkles, promotes elasticity, exhibits excellent activity of PPAR alpha, And exhibits an effect of improving the skin moisturization due to an increase in the expression of pillar green, as well as an effect of improving the skin texture due to the improvement of the skin brightness, so that it can be used for manufacturing pharmaceutical preparations, cosmetics, food or skin external preparation formulations.

In addition, Prim-O-glucosylcimifugin promotes the proliferation of dermal stem cells and exhibits a stem cell-retaining effect, and thus can be used for the production of cosmetic formulations for promoting stem cell activity.

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

To regenerate skin, improve wrinkles, improve elasticity, improve atopic skin, moisturize skin, and improve skin texture, it is necessary to use high-active skin regeneration, wrinkle improvement, elasticity improvement, atopy improvement, skin moisturizing And exhibits skin-modifying activity, exhibits excellent ability to permeate and absorb the skin, has low volatility so that it can stay for a sufficient time to exhibit skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement, skin moisturizing and skin texture improving effect , It is preferable that the active ingredient is kept stably on the composition or on the skin, and it is easy to formulate into pharmaceuticals, cosmetics, foods, skin external preparations and the like, and is safe for 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, skin moisturizing and skin tone improving ingredients may be used for skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement, skin moisturizing, But it is difficult to apply to real skin because of its ability to permeate through the skin and be absorbed. 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, skin moisturization and skin texture improvement components may be decomposed or converted into other compounds when exposed to heat, light or oxygen, Sometimes the effect disappears.

As can be seen in the following examples, Prim-O-glucosylcimifugin exhibits excellent collagen synthesis promotion effect, PPAR alpha activity effect, pilar green expression effect and skin brightness improvement effect at a low concentration, , Atopy improvement, skin moisturization and skin texture improvement, cosmetics, food, skin external agent, and the like.

Accordingly, the present invention provides a composition for improving skin regeneration, wrinkle improvement, elasticity enhancement, atopic improvement, skin moisturization and skin texture improvement comprising a compound represented by the following formula (1) as an active ingredient.

[Chemical Formula 1]

The compound of Chemical Formula 1 is named 5H-Furo [3,2-g] [1] benzopyran-5-one and 7 - [(? - D-; glucopyranosyloxy) methyl] -2,3- 1-hydroxy-1-methylethyl) -4-methoxy-, (2S) - and is also called Prim-O-glucosylcimifugin.

The compound of formula (1) may be synthesized or a commercially available compound may be used.

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

Accordingly, the composition of the present invention may comprise a pharmaceutically acceptable salt of the compound of formula (1).

The pharmaceutically acceptable salt of the compound of Formula 1 may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid The organic acid may be selected from the group consisting of hydrochloric acid, hydrobromic acid, hydrochloric acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, , Benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid-based salts, and the inorganic acid includes, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.

The above-mentioned acid addition salts may be obtained by a) directly mixing the compound of formula 1 and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Lt; RTI ID = 0.0 > acid < / RTI > in a solvent and mixing them.

In addition to the above, additionally saltable forms include, but are not limited to, the salts of gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, Aspartate and the like.

The composition may further contain one or more active ingredients exhibiting the same or similar functions. For example, it may contain known skin regeneration, wrinkle improvement, elasticity enhancement, atopic improvement, skin moisturizing and skin tone improving ingredients. When the composition contains additional skin regeneration, wrinkle improvement, elasticity enhancement, atopic improvement, skin moisturizing and skin texture improving ingredients, the skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement, skin moisturization and skin texture improvement effect . 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 and includes one or more species selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract Component. ≪ / RTI > The additional component may be included in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content range may be adjusted according to requirements such as skin safety, ease of formulation of the compound of Formula 1 .

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, which may 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.

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 restoration of skin tissue against damage caused by external or internal causes of the skin. Damage due to external causes may include ultraviolet rays, external contaminants, wound, trauma, etc. The damage caused by the internal causes 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 'moisturizing effect' refers to inhibiting or reducing the reduction of moisture in the skin, or increasing the moisture content of the skin to smooth and smooth the surface of the skin.

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 effective to promote regeneration of damaged skin, improve wrinkles, improve elasticity, improve dry skin such as atopic dermatitis, improve moisturizing effect, Means the amount of the compound. When the composition of the present invention contains an effective amount of the compound of Formula 1, the skin regeneration effect, the wrinkle improving effect, the elasticity improving effect, the atopy improving effect, the moisturizing effect and the skin texture improving effect can be provided. An effective amount of the compound of formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, how the compound is applied to the skin, and the time on the skin. For example, when the composition is produced into a pharmaceutical formulation, it may contain the compound of Formula 1 at a higher concentration than when it is commercialized as cosmetics that are routinely applied to the skin. 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 compound of formula (1) 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.

Further, the composition for improving skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement, skin moisturization and skin texture improvement of the present invention can be used for the preparation of external preparation for skin.

When the compound of formula (1) is used as an external preparation for skin, it 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, , 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 compound of Formula 1 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.

In addition, the composition for improving skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement, skin moisturizing and skin texture improvement of the present invention can be used for manufacturing 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.

The cosmetic composition may further contain, in addition to the compound of Formula 1, a lipid, 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, a fragrance, , 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 And may contain adjuvants commonly used in the cosmetics field, such as any of the other ingredients.

The cosmetic formulation may contain a relatively high concentration of the compound of formula (1) in the case of a wash-off type cosmetic such as a makeup 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, It may be included. In one embodiment of the present invention, although not limited thereto, the composition may contain 0.0001 wt% to 10 wt% (preferably 0.0001 wt% to 1 wt%) of the compound of Formula 1 based on the total weight of the composition . When the composition of the present invention contains less than 0.0001% by weight of the compound of formula 1, sufficient skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement, skin moisturizing and skin texture improvement effects can not be expected, It is intended to prevent such an undesirable reaction such as allergies or a problem in skin safety.

Further, the composition for improving skin regeneration, wrinkle improvement, elasticity improvement, atopic improvement, skin moisturizing and skin texture improvement of the present invention can be used for manufacturing food formulations.

The food formulation refers to food prepared by adding the compound of Formula 1 to food materials such as beverage, tea, spice, gum, confectionery, etc., or by encapsulation, powdering, suspension or the like.

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

When the compound of Chemical Formula 1 is used as a food additive, the compound of Chemical Formula 1 may be added as it is or may be used together with other food or food ingredients, and may 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 promoting stem cell activity comprising the compound of Formula 1 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, 'stem cell activity promoting effect' refers to a stem cell proliferation promoting effect and / or a stem cell maintaining effect.

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 the compound of formula (1).

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.

Reference Example  One: Prim -O- glucosylcimifugin  Material Information

[Chemical Formula 1]

CAS No .: 80681-45-4

Where to buy: Sichuan Hongjie Import & Export CO., LTD

Reference Example  2: Serum-free Under medium conditions  Cultivation of dermal stem cells

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). 1 / / mL of the compound of the formula (1) was treated with CNT-57 medium containing no BPE, ₂ and 37 < 0 > C for 72 hours.

Experimental Example  One: CCK Promoting the proliferation of skin stem cells through the -8 evaluation method

The skin stem cells cultured in Reference 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. The proliferation rate (%) of the compound of the formula (1) was determined from the measured absorbance value according to 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 The compound of formula (1) 1 / / mL 216% Control group - 100%

As shown in Table 1, the skin stem cells under the medium condition treated with the compound of the formula (1) showed an excellent proliferation promoting effect.

Experimental Example  2: Stem Cellularity of Dermal Stem Cells 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 Reference 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) The compound of formula (1) 1 / / mL 2.1 Control group - 1.0

As shown in Table 2, the medium condition treated with the compound of Formula 1 promotes the expression of p63 in dermal stem cells, and thus has excellent stem cell retention effect.

Example  1: Promoting collagen synthesis

The compound of Chemical Formula 1 was added to the culture medium of human 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).

The compound of formula (1) was added to the culture medium of human fibroblasts (7 x 10 ⁴ cells / cm ² ) together with vitamin C and a control (no addition) to give final concentrations of 10 μg / mL and 20 μg / 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 The compound of formula (1) 10 [mu] g / mL 35.0% The compound of formula (1) 20 / / mL 48.2% Vitamin C 50 / / mL 30.6%

As shown in Table 3, the compound of Chemical Formula 1 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 compound of formula (1), the following experiment was conducted using the compound of formula (1). 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 compound of formula (1) was treated and incubated 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 compound of Chemical Formula 1 was treated with C2C12 cells to measure the activity of PPAR alpha according to the concentration. The results are shown in Table 7 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 uM) 280 Wy-14,643 (1 uM) 935 Compound (1) (0.05%) 641 The compound of Formula 1 (0.5%) 948

As shown in Table 4, it was confirmed that the compound of the formula (1) showed a very strong PPAR alpha activity when compared with the positive control.

Example  3: Filaggrin's  Promoting effect of expression

The cells were incubated for 1 day in a culture medium of human keratinocyte HaCaT cells at a concentration of 5 μg / mL and 10 μg / mL, respectively. Then, the RNAs of the cells were isolated, cDNA was synthesized, Real-time PCR was performed. The RNA concentration was normalized to S16 ribosomal RNA.

Effect of expression of pillar green depending on concentration (number of repeats = 3) Additive sample Increase in pillar green compared to control Control group (no addition) 1.00 Compound (1) (5 / / mL) 28.4 The compound of formula (1) (10 [mu] g / mL) 43.1

As shown in Table 5, the compound of Chemical Formula 1 has the ability to promote pilar green expression of human horny cell line HaCaT cells.

Example  4: To improve the turn-over of the skin  About 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 9 below.

Skin brightness improvement effect division Four days after application Eight days after application After 12 days of application Improvement rate (%) 1.52 4.63 11.02

As shown in Table 6, when the nutritional cream according to the present invention was used, it was found to have the effect of improving the exfoliation of the skin.

Formulation example  1: Preparation of pharmaceutical preparations

1. Preparation of tablets

0.2 mg of the compound of formula (1)

100 mg of corn starch

100 mg of milk

Stearic acid  Magnesium 2 mg

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

A nutritional cream containing the compound of formula (1) as an active ingredient was prepared according to a conventional method, as shown below.

0.2% by weight of the compound of formula (1)

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

An ointment containing the compound of formula (I) as an active ingredient was prepared according to a conventional method, as shown below.

0.5% by weight of the compound of formula (1)

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 improving skin regeneration or wrinkling comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

The method according to claim 1,
A composition for skin regeneration or wrinkle improvement, wherein the composition is for the manufacture of a pharmaceutical, cosmetic, food or external preparation for skin regeneration or wrinkle improvement.
A composition for promoting skin elasticity comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

The method of claim 3,
Wherein the composition is for the preparation of a pharmaceutical composition for promoting skin elasticity, a cosmetic composition, a food or an external preparation for skin.
A composition for improving atopy comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

6. The method of claim 5,
Wherein the composition is for the manufacture of a pharmaceutical composition for atopic amelioration, a cosmetic preparation, a food or an external preparation for skin.
A composition for skin moisturizing comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

8. The method of claim 7,
Wherein the composition is for the preparation of pharmaceutical preparations for the skin moisturizing, cosmetic, food, or external preparation for skin.
A composition for improving skin texture comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

10. The method of claim 9,
Wherein the composition is for the manufacture of a pharmaceutical, cosmetic, food or skin topical formulation for improving skin texture.
A composition for stimulating stem cell activity comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

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 preparation for promoting stem cell activity.