KR102562468B1 - Composition for improving skin - Google Patents

Abstract

The present invention relates to a composition for improving skin. The compound represented by Formula 1 according to the present invention can be used for skin regeneration and/or skin texture improvement medicine, cosmetics, or food production through the effect of promoting proliferation of skin stem cells and improving skin brightness. In addition, it promotes the proliferation of skin stem cells and shows the effect of maintaining stem cell properties, so it can be used in the manufacture of cosmetics for promoting stem cell activity.

Description

Composition for improving skin {Composition for improving skin}

The present invention relates to a composition for skin improvement that exhibits skin regeneration, skin texture improvement, and stem cell activation promoting effects.

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 by age and region. Skin texture is divided into primary (about 20-100 μm), secondary (about 5-40 μm), and tertiary (about 0.5 μm) lines according to the depth of the lines. It is characterized by distinct polygons and star formation formed by the meeting of lines [Non-Patent Document 1]. However, it is known that with age or as the skin is damaged, the network structure of dense fine lines collapses, the fine lines (secondary, tertiary, etc.) disappear and the primary lines become deeper and wrinkles are formed [non-patented Literature 2]. In other words, wrinkles, a representative sign of skin aging, are the accumulation of minute changes that have already occurred over a long period of time.

Embryologically, it is known that all components of human skin are derived from ectoderm or mesoderm. Epidermis, hair follicles, sebaceous and sweat glands originate from the ectoderm, and melanocytes, nerves and special sensory receptors originate from the neuroectoderm. Depending on the developmental stage, stem cells in the embryo repeatedly differentiate to become cells with characteristics suitable for each tissue function, and even after becoming an adult, a certain number of stem cells remain in tissues. Stem cells mainly exist in two places in the skin. . The first is in the hair follicle. This area is known to play an important role in regeneration of the epidermis as a cell before cell differentiation occurs, and also plays an important role in regeneration and growth of hair. The second is the basal layer of epidermis. It has been revealed that the stem cells located here play an important role in maintaining skin health by managing not only the epidermis but also the fibroblasts in the dermal layer. Stem cells here are widely used in skin stem cell research because they have the advantage of being relatively large and easy to obtain. The skin is continuously regenerated, and stem cells present in the epithelium of the skin, ie, epidermal stem cells of the skin, are involved in epithelial recovery after injury [Non-Patent Document 3]. The epithelial stem cells of the skin are also referred to as skin stem cells, and when the skin stem cells are activated, skin wounds such as trauma can be treated or wound healing can be promoted, and wrinkle relief of the skin can also be expected. there is. Integrin β1 and integrin α6 are used as indicators of skin stem cells, and it has been reported that the maintenance of skin stem cells necessary for epithelial morphogenesis and differentiation is regulated by p63 protein.

Skin stem cells play an important role in maintaining skin health and physiological and biochemical homeostasis. Stem cells present in the skin also malfunction due to the effects of aging, and as a result, various problems occur as the homeostasis of the skin is broken. Therefore, it will be possible to improve various phenomena of skin aging through the activity of these stem cells [Non-Patent Document 4].

In addition, there is an urgent need for the development of ingredients that are safe for the body, stable active ingredients, and above all, have skin regeneration and skin texture improvement activities that are more effective than existing substances with skin regeneration and skin texture improvement effects.

Journal of the European Academy of Dermatology and Venereology. 12:103-114, 1999 The British journal of dermatology. 110: 129-138, 1984 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 inventors of the present invention found that the compound represented by Formula 1 promotes the proliferation of skin stem cells and maintains stem cell properties to promote skin regeneration, along with an effect of improving skin texture due to skin brightness improvement, The present invention was completed by confirming the effect of promoting proliferation and maintaining stem cell activity.

[Formula 1]

Accordingly, an object of the present invention is to provide a composition for skin regeneration and/or skin texture improvement comprising the compound represented by Formula 1 or an acceptable salt thereof as an active ingredient.

In addition, another object of the present invention is to provide a composition for promoting stem cell activity comprising the compound represented by Formula 1 or an acceptable salt thereof as an active ingredient.

As a means for solving the above problems, the present invention provides a composition for skin regeneration and/or skin texture improvement comprising a compound represented by Formula 1 below or an acceptable salt thereof as an active ingredient for the manufacture of medicines, cosmetics, or foods. to provide.

[Formula 1]

As another means for solving the above problems, the present invention provides a composition for promoting stem cell activity comprising a compound represented by Formula 1 below or an acceptable salt thereof as an active ingredient for preparing a cosmetic formulation.

[Formula 1]

The compound represented by Formula 1 according to the present invention promotes the proliferation of skin stem cells and maintains stem cell properties to promote skin regeneration and exhibits an effect of improving skin texture by improving skin brightness, thereby manufacturing medicine, cosmetics or food can be used for

In addition, the compound represented by Formula 1 promotes the proliferation of skin stem cells and exhibits the effect of maintaining stem cell properties, and thus can be used in the preparation of cosmetic formulations for promoting stem cell activity.

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

In order for skin regeneration and skin texture improvement ingredients to exert excellent effects when applied to the actual skin, they must exhibit high activity of skin regeneration and skin texture improvement at low concentrations, have excellent ability to penetrate and absorb through the skin, and promote skin regeneration and skin texture. It is desirable to have low volatility so that it can stay for a sufficient time to exhibit an improvement effect, to keep the active ingredient stable on the composition or skin, to be easy to manufacture into medicines, cosmetics or foods, and to be safe for the skin. However, among known components, components satisfying all of the above characteristics are not common. For example, some skin regeneration, wrinkle improvement, and skin texture improvement ingredients have excellent skin regeneration and skin texture improvement activities even at low concentrations in in vitro experiments, but their ability to penetrate and absorb is poor, making them difficult to apply to actual skin. Other active ingredients are difficult to formulate as medicines, cosmetics, or foods due to their low hydrophilicity. In addition, some skin regeneration and skin texture improvement ingredients are decomposed or transformed into other compounds when exposed to heat, light, or oxygen, and the effect may already disappear before application to the skin.

As can be seen in the following examples, the compound represented by Formula 1 exhibits an excellent skin stem cell proliferation promotion effect and skin brightness improvement effect at low concentrations, so it is a pharmaceutical, cosmetic, or food composition for skin regeneration and skin texture improvement can be used as an active ingredient in

Accordingly, the present invention provides a composition for skin regeneration and skin texture improvement comprising lithospermic acid, a compound represented by Formula 1 below, as an active ingredient.

[Formula 1]

The compound name of the compound of Formula 1 is (2S,3S)-4-[(E)-3-[(1R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]-3- Oxoprop-1-enyl]-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-3-carboxylic acid ((2S,3S)-4 -[(E)-3-[(1R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]-3-oxoprop-1-enyl]-2-(3,4-dihydroxyphenyl)-7- hydroxy-2,3-dihydro-1-benzofuran-3-carboxylic acid), also known as monardic acid A.

The compound represented by Formula 1 may be synthesized and used, or a commercially available compound may be used.

In addition, the composition of the present invention may include an acceptable salt of the compound represented by Formula 1 above. The acceptable salt of the compound represented by Formula 1 may be a pharmaceutically, cosmetically or food-acceptable salt, and the pharmaceutically-, cosmetically- or food-acceptable salt may be an acid addition salt formed using an organic acid or an inorganic acid. The organic acid is, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid , glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxyacetic acid, benzenesulfonic acid, p-toluenesulfonic acid, and methanesulfonic acid-based salts, and inorganic acids such as hydrochloric acid, bromine acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid based salts. It may be preferably in the form of hydrochloride or acetate, more preferably in the form of hydrochloride.

The above-mentioned acid addition salt is obtained by a) directly mixing the compound represented by Formula 1 and an acid, b) dissolving one of them in a solvent or aqueous solvent and mixing, or c) compound represented by Formula 1 It is prepared by a general salt preparation method in which a solvent or an acid in a submerged solvent is placed and mixed with them.

In addition to the above, additionally saltable forms include gaba salt, gabapentin salt, pregabalin salt, nicotate, adipate salt, hemimalonate, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt, Aspartate, etc.

In the present invention, the 'skin regeneration effect' refers to the recovery of skin tissue against damage caused by external and internal skin causes as the activity of skin stem cells is promoted. At this time, the damage caused by the external cause may include ultraviolet rays, external contaminants, wounds or trauma, and the like, and the damage caused by the internal cause may include stress. Preferably, the skin regeneration is related to skin stem cells that play an important role in maintaining skin health and physiological and biochemical homeostasis, and maintenance of skin stem cell properties necessary for epithelial morphogenesis and differentiation is regulated by p63 protein. do. Therefore, by treating the active ingredient of the present invention, the skin regeneration effect can be remarkably enhanced by promoting the proliferation of skin stem cells and maintaining skin stem cell properties.

In the present invention, the 'skin texture improvement effect' refers to smoothing the skin surface, imparting gloss, and brightening the skin tone by suppressing or inhibiting the roughening of the skin surface due to the effects of aging, stress, etc. .

The composition of the present invention can be used for the preparation of pharmaceutical formulations.

The pharmaceutical formulation may be in the form of a solution, suspension or emulsion in an oily or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule.

In addition, the composition may further contain one or more active ingredients exhibiting the same or similar functions. For example, known skin regeneration and/or skin texture improving ingredients may be included. When an additional skin regeneration and/or skin texture improvement component is included, the skin regeneration and/or skin texture improvement effect of the composition of the present invention can be further enhanced. When adding the above components, skin safety according to combined use, ease of formulation, and stability of active ingredients may be considered. In one embodiment of the present invention, the composition is a skin regeneration component known in the art, retinoic acid, TGF, animal placenta-derived protein, betulinic acid and chlorella extract, as an antioxidant component known in the art, tocopherol, selenium , vitamin C and phenolic compounds, whitening ingredients known in the art, substances that inhibit tyrosinase enzyme activity such as kojic acid and arbutin, hydroquinone, vitamin-C (L- Ascorbic acid) and derivatives thereof and various plant extracts may further include one or more components selected from the group consisting of. Additional components 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 and ease of formulation of the compound represented by Formula 1. There will be.

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

Pharmaceutically acceptable carriers may contain various ingredients such as buffer, sterile water for injection, normal saline or phosphate buffered saline, sucrose, histidine, salts and polysorbates.

The composition of the present invention can be administered orally or parenterally, and can be administered in the form of general pharmaceutical formulations, for example, in various oral and parenteral formulations for clinical administration, and when formulated, commonly used fillers and extenders , It may be prepared using diluents or excipients such as binders, wetting agents, disintegrants, and surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations contain at least one excipient, for example, starch, calcium carbonate, water, etc., in the pharmaceutical composition of the present invention. It may be prepared by mixing sucrose or lactose, gelatin, and the like.

In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included.

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.

The pharmaceutical formulation of the present invention may include a formulation for external application to the skin.

When the compound represented by Formula 1 is used as an external skin preparation, additionally 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, a fragrance, Surfactants, 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 It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients commonly used in skin care. In addition, the components may be introduced in an amount generally used in the field of skin science.

When the compound represented by Formula 1 is provided as an external formulation for skin, it may have formulations such as ointments, patches, gels, creams, or sprays, but is not limited thereto.

In addition, the composition for skin regeneration and/or skin texture improvement of the present invention may be used for preparing cosmetic formulations.

The cosmetic formulation may be in the form of a general emulsified formulation and a solubilized formulation. For example, lotion such as softening lotion or nourishing lotion, emulsion such as facial lotion, body lotion, etc., cream such as nourishing cream, moisture cream, eye cream, essence, cosmetic ointment, spray, gel, pack, sunscreen, makeup base, liquid It may have formulations such as foundation, powder, cleansing cream, cleansing lotion, makeup remover such as cleansing oil, cleanser such as cleansing foam, soap, body wash, and the like.

In addition to the compound represented by Formula 1, the cosmetics may include 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, a fragrance, a surfactant, Water, ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, humectants, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or commonly used in cosmetics It may contain adjuvants commonly used in the field of cosmetology, such as any other ingredients that are

The cosmetic formulation may contain the compound represented by Formula 1 at a relatively high concentration in the case of wash-off type cosmetics such as make-up removers and cleansers in which active ingredients stay on the skin for a short period of time. On the other hand, in the case of leave-on type cosmetics such as lotion, emulsion, cream, essence, etc. in which active ingredients stay on the skin for a long time, compared to wash-off type cosmetics, the formula (1) at a lower concentration It will be okay even if it includes a compound. Although not limited thereto, in one embodiment of the present invention, the composition contains the compound represented by Formula 1 in an amount of 0.0001% to 10% by weight (preferably 0.0001% to 1% by weight) based on the total weight of the composition. can include When the composition of the present invention contains less than 0.0001% by weight of the compound represented by Formula 1, a sufficient skin regeneration effect and skin texture improvement effect cannot be expected, and when it contains more than 10% by weight, unwanted effects such as allergies may occur. This is to prevent a reaction or skin safety problem.

In the present invention, 'effective amount' means the amount of the compound represented by Formula 1 that can promote regeneration of damaged skin or improve skin texture. When the composition of the present invention contains an effective amount of the compound represented by Formula 1, it is possible to provide desirable skin regeneration and skin texture improvement effects. The effective amount of the compound represented by Formula 1 included 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 how long it stays on the skin. For example, when the composition is commercialized as a pharmaceutical formulation, it may contain the compound represented by Formula 1 at a higher concentration than when commercialized as a cosmetic product that is routinely applied to the skin. Therefore, 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 represented by Formula 1, It may be administered 1 to 6 times.

The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

In addition, the composition for skin regeneration and/or skin texture improvement of the present invention may be used for preparing a food formulation.

The food formulation refers to a food prepared by adding the compound represented by Formula 1 to food materials such as beverages, teas, spices, chewing gum, and confectionery, or encapsulated, powdered, or suspended.

Since the food formulation can be consumed on a daily basis, it is very useful because a high skin regeneration effect and skin texture improvement effect can be expected.

When the compound represented by Formula 1 is used as a food additive, the compound represented by Formula 1 may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, when preparing food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, 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 above the above range. .

There is no particular limitation on the type of food. Examples of foods to which the substance can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and includes all health foods in a conventional sense.

When the food formulation is a beverage, it may contain various flavoring agents or natural carbohydrates as additional ingredients, as in conventional beverages. The aforementioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used. The proportion 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, food formulations include various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonated beverages It may contain a carbonation agent used for Other food formulations may contain fruit flesh for the production of natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The ratio of these additives is not very important, 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 represented by Formula 1 as an active ingredient.

In the present invention, the term 'stem cell' is a cell that can divide itself and has the ability to differentiate into a very diverse specific cell type. The type of these stem cells is not particularly limited, and in one embodiment, the stem cells may be skin stem cells. The 'skin stem cells' refer to stem cells capable of differentiating into cells constituting the skin (epidermis, dermis, and subcutaneous fat layer). Cells forming the skin include keratinocytes present in the epidermis, melanocytes present in the epidermis, and fibroblasts present in the dermis (mainly responsible for the biosynthesis of collagen and elastin).

The type of skin stem cells is not particularly limited. Skin stem cells used in the present invention can be used regardless of where they originate. For example, skin stem cells can be obtained from known sources of skin stem cells, such as hair follicles or the basal layer of the epidermis, and the animal to be collected may be a mammal. In one embodiment, a mammal can include, but is not limited to, a human, mouse, rat, guinea pig, rabbit, monkey, pig, horse, cow, sheep, antelope, dog, or cat. Preferably the mammal may be a human. Such a method for obtaining skin stem cells from a skin stem cell source is well known in the art.

In the present invention, the 'stem cell activity promoting effect' refers to the effect of promoting stem cell proliferation and/or maintaining the specific indicator molecule of stem cells and stem cell nature, which is the property of self division. The maintenance of stem cell nature is an effect that occurs when stem cells are treated with the compound represented by Formula 1, by promoting the expression of p63, an intracellular transcription factor and a maintenance marker for skin stem cells.

In addition, the composition of the present invention can be used for the preparation of cosmetic formulations. These cosmetic formulations are the same as those described in the description of cosmetic formulations containing the compound represented by Formula 1 above.

Hereinafter, examples and the like will be described in detail to aid understanding of the present invention. However, the embodiments according to the present invention can be modified in many different forms, and the scope of the present invention should not be construed as being limited to the following examples. Embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

reference example One: Lithospermic acid Substance information

[Formula 1]

CAS No.: 28831-65-4

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

reference example 2: serum free in the medium condition of skin stem cells culture

Human epidermal stem cells purchased from Cellntec were placed in a 48-well plate (6×10 ³ cells/well), and BPE (Bovine pituitary extract) similar to fetal bovine serum was added. CNT-57 medium (Cellntec) was used for 24 hours in 5% CO ₂ and cultured at 37°C. Then, the culture medium was removed through the suction tube, and then the medium components were removed using a PBS solution (GibcoBRL), and the CNT-57 medium without BPE was treated with 10 μg/mL of the compound represented by Formula 1 to obtain 5 It was cultured for 72 hours under % CO ₂ and 37°C conditions.

Example One: CCK -8 Through the evaluation method skin stem cells Proliferative effect

CCK-8 (Cell counting kit-8) evaluation was performed on the skin stem cells cultured in Reference Example 2. CCK-8 evaluation is an analysis method that indirectly indicates the density of living cells by measuring the absorbance of formazan produced by dehydrogenase in the intracellular electron transport chain decomposing tetrazolium salt.

The cells were treated with a CCK-8 solution (1/10 of the volume of the medium) at 37° C. for 2 hours, and then the absorbance at 450 nm was measured spectrophotometrically. For the proliferation promoting effect of the compound of Formula 1, the proliferation rate (%) was calculated according to Equation 1 below compared to the control group (CNT-57 medium supplemented with BPE) from the measured absorbance value, and the values are shown in Table 1 below. .

[Equation 1]

Proliferation rate (%) = (absorbance of sample treatment group / absorbance of control group) × 100

Skin stem cell proliferation promotion effect (number of repetitions = 3) Additive sample density Cell proliferation rate (%) compared to the control group Compound of Formula 1 10 µg/mL 138.7 control group - 100

As shown in Table 1, skin stem cells in the medium conditions treated with the compound of Formula 1 exhibited excellent proliferation promoting effects.

Example 2: of skin stem cells stem cell nature ( stemness ) check the retention effect

In order to confirm the effect of maintaining the stem cell nature of the skin stem cells cultured in Reference Example 2, the expression level of p63 was evaluated. As an intracellular transcription factor, p63 is well known as a maintenance marker for skin stem cells. Cellular RNA was isolated to synthesize cDNA, and real-time PCR was performed using Taqman staining solution to measure the level of p63 expression. 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 value of p63 increase fold means the fold compared to the control group (CNT-57 medium supplemented with BPE).

Stemness maintenance effect (repeat number = 3) Additive sample density p63 increase fold (fold) Compound of Formula 1 10 µg/mL 1.49 control group - 1.0

As shown in Table 2, the medium conditions treated with the compound of Formula 1 promote the expression of p63 in skin stem cells, resulting in an excellent stem cell maintenance effect.

Example 3: To improve turn-over About efficacy

For the nutritional cream of Formulation Example 2 below, the effect of improving keratin exfoliation was tested on healthy women in their 20s to 50s as follows.

A 1.5% solution of DHA (Dihydroxyacetone, Sigma Aldrich, USA) was deposited on the test site of 20 women aged 20 to 50 years by closing the patch for 8 hours, and then the preparation example nutrient cream was applied to the test site twice daily. 4 days after application, 8 days after application, and 12 days after application, instrumental measurement of the skin brightness of the deposition site was performed using a Chromameter CR-400 (Minolta, Japan) and pictures were taken using a DSLR. The measured value was evaluated by obtaining an average value of three times excluding the maximum and minimum values, and the higher the improvement in skin brightness of the deposition site, the higher the keratin exfoliation improvement effect. The results are shown in Table 3 below.

skin brightening effect division 4 days after application 8 days after application 12 days after application Improvement rate (%) 1.56 4.36 11.29

As shown in Table 3, it was found that there was an effect of improving keratin exfoliation when the nutrient cream according to the present invention was used.

formulation example 1: Preparation of pharmaceutical preparations

1. Preparation of tablets

Compound of Formula 1 0.2 mg

Corn Starch 100mg

lactose 100mg

Magnesium Stearate 2mg

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

formulation example 2: Manufacturing of cosmetics

1. Manufacture of nutritional cream

As shown in the following composition, a nutritional cream containing the compound of Formula 1 as an active ingredient was prepared according to a conventional method.

0.2% by weight of the compound of Formula 1

Beta-1,3-glucan 5.0% by weight

10.0% by weight of beeswax

Polysorbate 60 1.5% by weight

PEG 60 hydrogenated castor oil 2.0% by weight

Sorbitan sesquioleate 0.5% by weight

10.0% by weight of liquid paraffin

Squalane 5.0% by weight

Caprylic/capric triglyceride 5.0% by weight

Glycerin 5.0% by weight

Butylene glycol 3.0% by weight

Propylene glycol 3.0% by weight

Triethanolamine 0.2% by weight

Preservative 0.05% by weight

Pigment 0.05% by weight

Perfume 0.05% by weight

Purified water to 100% by weight

formulation example 3: Preparation of topical skin preparation

1. Preparation of ointment

As shown in the following composition, an ointment containing the compound of Formula 1 as an active ingredient was prepared according to a conventional method.

0.5% by weight of the compound of Formula 1

Beta-1,3-glucan 10.0% by weight

10.0% by weight of beeswax

Polysorbate 60 5.0% by weight

PEG 60 hydrogenated castor oil 2.0% by weight

Sorbitan sesquioleate 0.5% by weight

Vaseline 5.0% by weight

10.0% by weight of liquid paraffin

Squalane 5.0% by weight

Shea butter 3.0% by weight

Caprylic/capric triglyceride 5.0% by weight

Glycerin 10.0% by weight

Propylene glycol 10.2% by weight

Triethanolamine 0.2% by weight

Preservative 0.05% by weight

Pigment 0.05% by weight

Perfume 0.05% by weight

Purified water to 100% by weight

Claims (8)

A cosmetic composition for skin regeneration comprising a compound represented by Formula 1 below or an acceptable salt thereof as an active ingredient.
[Formula 1]

delete A cosmetic composition for improving skin texture comprising a compound represented by Formula 1 below or an acceptable salt thereof as an active ingredient.
[Formula 1]

A food composition for improving skin texture comprising a compound represented by Formula 1 below or an acceptable salt thereof as an active ingredient.
[Formula 1]
An external skin preparation for promoting keratin exfoliation by promoting stem cell activity, comprising a compound represented by Formula 1 below or an acceptable salt thereof as an active ingredient.
[Formula 1]

According to claim 5,
The stem cell activity is a skin external agent for promoting keratin exfoliation according to the promotion of stem cell activity, characterized by the promotion of stem cell proliferation or maintenance of stem cell nature.
According to claim 6,
The maintenance of stem cell nature promotes the expression of the p63 gene to maintain stem cell activity and promotes keratin exfoliation. delete