KR20170025350A - Composition for improving skin - Google Patents

Abstract

The present invention relates to a composition for improving skin condition. According to the present invention, a jujube extract shows effects of promoting proliferation of skin stem cells, and thus can be used for producing foods, cosmetic ingredients, or drugs for regenerating skin. Additionally, the jujube extract also promotes proliferation of skin stem cells and maintains stemness properties, thereby being useful for producing cosmetic ingredients for promoting activities of stem cells, as well as foods, cosmetic ingredients, or drugs for regenerating skin.

Description

[Composition for improving skin]

The present invention relates to a skin improving composition exhibiting skin regeneration and stem cell activity promoting effect.

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 recovery of the epithelium after injury [Non-Patent Document 1]. 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, various phenomena of skin aging can be improved through the activity of stem cells [Non-Patent Document 2].

In addition, it is urgently required to develop a composition having a skin regeneration activity that is safe for living body, stable in its effective component, and most effective for a skin regeneration effect.

On the other hand, it is known that the jujube (Zizyphus jujuba MILLER) belongs to the genus Zambia (Rhamanceae) and belongs to the jujube, Zizyphus. Its origin is North Africa and Western Europe. It is known that there are about 40 varieties and 400 varieties. Fruits are harvested in autumn, reddish brown, elliptical, ranging in length from 1.5 to 2.5 cm, and have a sweet taste when cooked red.

Jujube is mainly malic acid and contains a small amount of tannin. Jujube is also rich in vitamins, which are relatively abundant. Vitamin A 69 I. 100 g of dried jujube, vitamin B1 0.23 mg Vitamin B2 0.57 mg Vitamin C 188 to 544 mg Vitamin P is about 354 to 888 mg. Vitamin B6 is also rich in vitamin K and other. In particular, among the vitamin P, Rutin, Flavone and Flavone glycoside are contained, and the pharmacological effect is high. Saponin is also a major component of jujube, and it is evenly distributed throughout fruit, seed, leaf, stem, and roots. Other fruits also include the epicatechin leucocyanidin trimethylolagic acid betulonic acid Orea, a kind of comaroylate of maslinic acid, Oleanolic acid maslinic acid comaroylmaslinic acid alphitolic acid hydroxyursonic acid and the like. The term " oleanolic acid "

In 'Dongbokgop', it is said that 'jujube' has a power to strengthen the bowels and it is common sense to help the gyeongmaek to see the tribe. 'In the' Chinese medicine main building ',' Tribes, and harmonizes the nature of all kinds of medicines. " Other jujube has been known to have pharmacological effects such as analgesic, anticancer, antipyretic, sedative, hemostatic, tonic, and immunity enhancement.

Despite the many human efficacy of jujube, there have been no studies on dermal stem cells of jujube. Accordingly, the inventors of the present invention discovered an excellent stem cell proliferative effect of jujube in studying candidates capable of promoting the proliferation of stem cells in natural products, and completed the present invention.

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 jujube extract promotes the skin regeneration effect due to the promotion of proliferation of dermal stem cells, promotes proliferation of the dermal stem cells, exhibits the stem cell maintenance effect, It was completed.

Accordingly, it is an object of the present invention to provide a skin regeneration composition comprising a jujube extract as an active ingredient.

Another object of the present invention is to provide a composition for promoting stem cell activity comprising the jujube extract as an active ingredient.

As means for solving the above problems, the present invention provides a skin regeneration composition comprising a jujube extract as an active ingredient, for the production of medicines, cosmetics or foods.

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

The jujube extract according to the present invention promotes the proliferation of skin stem cells to promote regeneration of the skin, and thus can be used for the manufacture of medicines, cosmetics or foods.

In addition, the jujube extract 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.

In order to exert an excellent effect when the skin regeneration component is applied to actual skin, it is required to exhibit highly regenerated skin activity at a low concentration, have excellent ability to permeate and absorb the skin, Is low and the active ingredient is stably maintained on the composition or on the skin, and it is easy to manufacture into medicines, cosmetics, food or 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 components have excellent skin regeneration activity even at low concentration in vitro, but they are not able to be absorbed through the skin and applied to actual skin. Other active ingredients have low hydrophilicity, making them difficult to formulate into medicines, cosmetics, and foods. In addition, some skin regeneration components may be degraded or transformed into other compounds when exposed to heat, light, or oxygen, which may already have vanished before application to the skin.

As can be seen from the following examples, the jujube extract has an excellent effect of promoting the proliferation of skin stem cells superior in low concentration, and thus can be used as an active ingredient of medicines, cosmetics or food compositions for skin regeneration.

Accordingly, the present invention provides a skin regeneration composition comprising a jujube extract as an active ingredient.

In the present invention, the jujube (Zizyphus jujuba MILLER) is known as the genus Zizyphus, belonging to the genus Raminaceae (Rhamanceae) and the jujube.

The jujube 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 jujube extract may be an extract obtained by extracting jujube with 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, the jujube extract may contain a fraction obtained by fractionating the primary extract extracted using the above-described extraction solvent with an extraction solvent having a different polarity. For example, the jujube extract may 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 or hexane. 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, a known skin regeneration component may be included. The skin regeneration effect of the composition of the present invention may be further enhanced by including an additional skin regeneration component. 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 ingredient may be contained 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, easiness in formulation of the jujube extract.

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 "effective amount" means the amount of the extract that promotes regeneration of damaged skin. When the composition of the present invention contains an effective amount of the jujube extract, it can provide a desirable skin regeneration effect. The effective amount of the jujube extract contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, the method 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, the jujube extract may be contained at a higher concentration than in the case of cosmetics that are routinely applied to the skin. Therefore, the daily dose 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 jujube extract, ≪ / RTI >

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 jujube extract is used as an external preparation for skin, it may further contain at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickening and gelling agents, softening agents, antioxidants, suspending agents, stabilizing agents, foaming agents, , 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 external preparations for skin ≪ / RTI > any other ingredients that are commonly used in the skin sciences. The components can also be introduced in amounts commonly used in the field of dermatology.

When the jujube 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.

In addition, the skin regeneration composition 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 cream, a cleansing lotion, a make-up remover such as a cleansing oil, a cleansing foam, a soap, a body wash, and the like.

In addition, the cosmetic composition may further contain a lipid extract, 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, a surfactant, Or any other conventionally used in cosmetics such as nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, ≪ RTI ID = 0.0 > ingredients. ≪ / RTI >

The cosmetic formulation may contain a relatively high concentration of the jujube extract in the case of wash-off type cosmetics 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 and the like in which the active ingredient remains on the skin for a long period of time, It will be acceptable. In one embodiment of the present invention, but not limited thereto, the composition may contain the jujube extract in an amount of 0.0001 wt% to 10 wt% (preferably 0.0001 wt% to 1 wt%) based on the total weight of the composition . If the composition of the present invention contains less than 0.0001% by weight of the jujube extract, sufficient skin regeneration effect can not be expected. If the composition contains more than 10% by weight of the jujube extract, undesired reactions such as allergy may occur, This is to prevent this.

In addition, the skin regeneration composition of the present invention can be used for the production of food formulations.

The food formulation refers to a food prepared by adding the jujube 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 preparation can be ingested on a daily basis, a high skin regeneration effect can be expected, which is very useful.

When the jujube extract is used as a food additive, the jujube extract can be directly added or 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 promoting stem cell activity comprising the jujube extract 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 jujube extract.

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  1: Preparation of jujube extract

Jujube was washed, powdered, and then cooled in 10 times ethanol (w / v) 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). Then, the removal through the medium-introducing tube, and then, PBS solution used to remove the medium components the (GibcoBRL Co.), and the process of jujube extract, 5 ug / ml in the CNT-57 medium that does not include BPE 5% CO _2, and 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 values, the proliferation rate (%) of the jujube extract of the jujube extract was obtained from the control group (CNT-57 medium without extract) according to the following formula (1) .

[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 Jujube extract 5 / / mL 136% Control group - 100%

As shown in Table 1, the skin stem cells in the culture medium treated with jujube extract 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) Jujube extract 5 / / mL 2.14 Control group - 1.0

As shown in Table 2, the culture conditions in which the jujube extract was treated promoted the expression of p63 in dermal stem cells, and thus the stem cell maintenance effect was excellent.

Formulation example  1: Manufacture of pharmaceutical preparations

1. Preparation of tablets

Jujube extract 0.2 mg

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

A nutritional cream containing the jujube extract as an active ingredient was prepared according to a conventional method, as shown below.

Jujube extract 0.2 wt%

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 the jujube extract as an active ingredient was prepared by a conventional method.

Jujube extract 0.5 wt%

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 (7)

A composition for skin regeneration comprising a jujube extract as an active ingredient.
The method according to claim 1,
Wherein the jujube extract is an extract obtained by extracting jujube from 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, a cosmetic preparation or a food product.
A composition for promoting stem cell activity comprising jujube extract as an active ingredient.
6. The method of claim 5,
Wherein the composition is for promoting stem cell proliferation or stem cell retention.
6. The method of claim 5,
Wherein the composition is for the production of a cosmetic for promoting stem cell activity.