KR102472978B1 - Composition for improving skin - Google Patents

Abstract

The present invention relates to a composition for improving skin. Neoandrographolide according to the present invention promotes collagen synthesis in fibroblasts of the skin to promote skin regeneration, improve wrinkles, improve elasticity, scavenge free radicals to exhibit antioxidant effects, and inhibit NO production It has anti-inflammatory effect, suppresses melanin synthesis to show whitening effect, PPAR alpha activity is also excellent, so it has an effect of improving atopy, along with the effect of improving skin moisturization due to increased expression of filaggrin, and skin texture by improving skin brightness. By showing an improvement effect, it can be used as a pharmaceutical composition, skin external preparation, cosmetic composition or health food. In addition, it promotes the proliferation of skin stem cells and exhibits the effect of maintaining stem cell properties, so it can be used as a composition for promoting stem cell activity and a cosmetic containing the same.

Description

Composition for improving skin {Composition for improving skin}

The present invention relates to a composition for skin improvement such as skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening, and skin texture improvement.

Collagen is a major matrix protein produced by fibroblasts of the skin and is present in the extracellular matrix. Its important functions include mechanical robustness of skin, resistance and cohesiveness of connective tissue, support of cell adhesion, cell division and differentiation (of organisms). growth or wound healing) and the like are known. It is known that such collagen is reduced by age and photoaging caused by UV irradiation, which is closely related to wrinkle formation of the skin. In addition, as extensive research on skin aging has been developed in recent years, important functions of collagen in the skin have been revealed.

Active ingredients exhibiting an anti-wrinkle effect by promoting collagen synthesis are known. For example, retinoic acid, TGF (transforming growth factor) [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 substances promoting collagen synthesis. However, there is a problem in that the amount of the active ingredients used is limited due to safety problems such as irritation and redness when applied to the skin, or the effect of improving skin function by substantially promoting collagen synthesis in the skin cannot be expected because the effect is insignificant.

On the other hand, active oxygen introduced from the outside of the living body or generated inside the living body causes many problems such as accelerating aging of the living body or causing cancer. Therefore, a lot of development and research on antioxidant substances that inhibit oxidation by active oxygen have been made. Antioxidants are widely distributed in animals and plants, and many phenolic compounds, flavonoids, tocopherols, vitamin C, and selenium are known in fruits and vegetables. However, antioxidants present in nature cannot be expected to have a substantially sufficient effect when applied to the skin. Therefore, many synthetic antioxidants with excellent antioxidant power and low price are used, but their use is limited due to safety concerns such as side effects on the human body.

In addition, inflammation is an immune response of the human body in response to wounds or diseases, and oxidative stress such as ultraviolet rays, active oxygen, and free radicals activates inflammatory factors to cause various diseases and aging of the skin. Vasoactive polypeptides, such as kinin, plasmin, and complement, act on vasodilation, contraction, and chemotaxis, and other lymphocytes such as interleukin-6 (IL-6) Phosphorus and arachidonic acid are responsible for the inflammatory response. Arachidonic acid is metabolized into prostaglandin and leukotrienes, which are inflammatory mediators, through two pathways, cyclooxygenase and lipooxygenase, and mediates various inflammatory responses.

On the other hand, in order to disappear inflammation, it is called an anti-inflammatory agent that acts to remove the inflammatory source and reduce the physiological response and symptoms. Substances that have been used for anti-inflammatory purposes so far include flufenamic acid, ibuprofen, benzydamine, indomethacin, etc. as nonsteroidal agents, and prednisolone as steroidal agents. , dexamethasone, and the like. In addition, allantoin, Azene, hydrocortisone, etc. are known to be effective in anti-inflammatory, but these substances have limitations in usage due to safety issues on the skin, or the effect is insignificant, so the anti-inflammatory effect cannot be expected. there is

In addition, the epidermis located at the outermost layer of the skin performs a protective function of defense against various external physical, chemical and mechanical stimuli and preventing excessive dissipation of moisture in the body through the skin. This protective function is possible because the stratum corneum composed of keratinocytes is normally formed and maintained. Keratinocytes are cells formed through step-by-step morphological and functional changes as basal cells that continuously proliferate in the stratum basale migrate to the stratum corneum. After a certain period of time, old keratinocytes Forming cells are shed from the skin, and new keratinocytes rising from the lowermost layer of the epidermis repeat the process of epidermis differentiation or keratinization in place of their functions. During this keratinization process, keratinocytes produce Natural Moisturizing Factor (NMF) and intercellular lipids such as ceramide, cholesterol, and fatty acids, so that the stratum corneum acts as a barrier layer against the outside, forming a skin barrier. will have a function as

In addition, xeroderma, which is considered one of the major diseases of modern society, is one of the symptoms caused by abnormal skin barrier function. Recently, environmental pollution, an increase in dry environments such as apartments and high-rise buildings, an increase in social stress, and It is increasing more and more due to various factors such as excessive bathing culture and skin aging, and the number of cases requiring treatment due to severe symptoms is also continuously increasing.

Atopic dermatitis, which has recently occurred in 10% of children, is also known to be caused by dry skin, more fundamentally, abnormal skin barrier function. In order to treat such atopic dermatitis, conventionally, a lot of research has been conducted to supply moisture from the outside or minimize moisture loss from the body by focusing on maintaining appropriate moisture in the skin. Moisturizers such as ceramide) or its derivatives have been developed and are widely used in pharmaceutical or cosmetic fields.

However, most of the use of such moisturizers are only temporary relief of symptoms rather than fundamental treatment, and thus do not show sufficient effects for the treatment of dry skin including atopic dermatitis and abnormal skin barrier function. Accordingly, there is an urgent need to develop a material that fundamentally regenerates the damaged skin barrier.

Recently, it is known that when Peroxisome Proliferator Activated Receptor-alpha (PPAR alpha) present in keratinocytes binds to its ligand and is activated, it promotes the differentiation of keratinocytes to reconstruct the damaged skin barrier. In fact, when clofibrate [Non-Patent Document 2] or WY14643 [Non-Patent Document 3], a known PPAR alpha agonist, is applied to skin with damaged skin barrier, differentiation of keratinocytes is promoted. It has been confirmed that it promotes the recovery of the skin barrier.

In addition, having white and fair skin is a constant desire of everyone. It is genetically determined according to the concentration and distribution of melanin in human skin, but it is also affected by environmental or physiological conditions such as solar ultraviolet rays, fatigue, and stress. Melanin is produced through a non-enzymatic oxidation reaction after conversion to DOPA and dopaquinone by the action of an enzyme called tyrosinase on tyrosine, a kind of amino acid. Although the pathway by which melanin is produced is known, the mechanism that induces melanin synthesis, which is the previous step in which tyrosinase acts, has not yet been clarified in detail.

On the other hand, as general known whitening ingredients, substances that inhibit tyrosinase enzyme activity such as kojic acid and arbutin, hydroquinone, vitamin-C (L-Ascorbic acid) and derivatives thereof, and various There are plant extracts. By inhibiting the synthesis of melanin pigment, they can brighten the skin tone and realize skin whitening, as well as improve skin hyperpigmentation such as spots and freckles caused by ultraviolet rays, hormones, or heredity. However, when applied to the skin, there is a problem in that the amount of use is limited due to safety problems such as irritation and redness, or a practical effect cannot be expected because the effect is insignificant.

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 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 4].

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 5]. 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 6]. 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. have. 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 7].

In addition, it is safe for the body, active ingredients are stable, and above all, skin regeneration that is more effective than substances with existing skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement effects , Wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening, and development of ingredients having skin texture improvement activities are desperately desired.

Japanese Patent Publication Hei 8-231370 Japanese Unexamined Patent Publication Hei 8-208424 Japanese Unexamined Patent Publication Hei 9-40523 Japanese Patent Publication Hei 10-36283

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

Accordingly, the present inventors found that Neoandrographolide promotes collagen synthesis of skin fibroblasts to promote skin regeneration, improve wrinkles, enhance elasticity, scavenge free radicals to exhibit antioxidant effects, and NO It has an anti-inflammatory effect by inhibiting melanin production, a whitening effect by inhibiting melanin synthesis, and an atopic improvement effect due to excellent PPAR alpha activity. The skin texture improvement effect due to was confirmed, and the present invention was completed by confirming the effect of promoting stem cell proliferation and the effect of maintaining stem cell properties.

Accordingly, an object of the present invention is to provide a composition for skin regeneration, wrinkle improvement, elasticity promotion, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement comprising a compound represented by Formula 1 as an active ingredient. :

[Formula 1]

In addition, another object of the present invention is to provide a composition for promoting stem cell activity comprising a compound represented by Formula 1 as an active ingredient and a cosmetic composition containing the composition:

[Formula 1]

Accordingly, the present inventors found that Neoandrographolide promotes collagen synthesis of skin fibroblasts and promotes proliferation of skin stem cells to promote skin regeneration, improve wrinkles, improve elasticity, and reduce free radicals. It has anti-oxidant effect by eliminating NO production, anti-inflammatory effect by suppressing NO production, whitening effect by inhibiting melanin synthesis, atopic dermatitis improvement effect due to excellent activity of PPAR alpha, and skin moisturizing due to increased expression of filaggrin. In addition to the improvement effect, the present invention was completed by confirming the skin texture improvement effect due to the improvement of skin brightness.

Accordingly, an object of the present invention is to provide a composition for skin regeneration, wrinkle improvement, elasticity promotion, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement comprising a compound represented by Formula 1 as an active ingredient. :

[Formula 1]

In addition, another object of the present invention is to provide a composition for promoting stem cell activity comprising a compound represented by Formula 1 as an active ingredient and a cosmetic composition containing the composition:

[Formula 1]

Neoandrographolide according to the present invention promotes collagen synthesis of skin fibroblasts, promotes skin regeneration, improves wrinkles, enhances elasticity, scavenges free radicals to exhibit antioxidant effects, and inhibits NO production. It has anti-inflammatory effect, suppresses melanin synthesis to show whitening effect, PPAR alpha activity is also excellent, so it has an effect of improving atopy, along with the effect of improving skin moisturization due to increased expression of filaggrin, and skin texture by improving skin brightness. By showing an improvement effect, it can be used in pharmaceuticals, cosmetics, or health foods. In addition, it promotes the proliferation of skin stem cells and exhibits the effect of maintaining stem cell properties, so it can be used as a composition for promoting stem cell activity and a cosmetic containing the same.

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

Skin regeneration, wrinkle improvement, elasticity improvement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening, and skin texture improvement ingredients are highly active at low concentrations to achieve excellent effects when applied to the actual skin, such as skin regeneration, wrinkle improvement, and elasticity enhancement , Atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement activity, excellent ability to be absorbed through the skin, skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, It is desirable that the volatility is low so that it can stay for a sufficient time to exhibit whitening and skin texture improvement effects, that the active ingredient is stably maintained on the composition or skin, that it is easy to formulate as a medicine or cosmetic, and that it is 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, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement ingredients are tested in vitro even at low concentrations for skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, and antioxidant , Anti-inflammatory, moisturizing, whitening and skin texture improvement activities are excellent, but the ability to penetrate and absorb through the skin is poor, making it difficult to apply to actual skin. Other active ingredients are difficult to formulate as medicines or cosmetics due to their low hydrophilicity. In addition, some skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement ingredients are decomposed or transformed into other compounds when exposed to heat, light, or oxygen. In some cases, the effect is lost even before you apply it to the skin.

As can be seen in the following examples, neoandrographolide has an excellent collagen synthesis promoting effect, antioxidant effect, anti-inflammatory effect, melanin production inhibitory effect, PPAR alpha activation effect, filaggrin expression effect, and skin brightness improvement at low concentration. Since it shows effects, it can be used as an active ingredient in medicines, cosmetics, and health foods for skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, skin whitening, and skin texture improvement.

Therefore, the present invention therefore provides a pharmaceutical composition for skin regeneration, wrinkle improvement, elasticity promotion, atopy improvement, antioxidant, anti-inflammatory, moisturizing, skin whitening and skin texture improvement comprising a compound represented by Formula 1 as an active ingredient. do.

[Formula 1]

The compound name of the compound of Formula 1 is 19-hydroxy-8(17),13-ravoiadiene-16,15-olide-o-βD-glucopyranoside (19-hydroxy-8(17), 13-laboiadien-16,15-olide-o-βD-glucopyranoside), also known as Neoandrographolide.

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

The pharmaceutical composition for skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement of the present invention may include 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 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 include, for example, hydrochloric acid, hydrobromic 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 of formula 1 and the acid, b) dissolving one of them in a solvent or aqueous solvent and mixing, or c) adding the compound of formula 1 to a solvent or aqueous solution. It is prepared by a general salt preparation method in which an acid in a 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 addition, when the compound represented by Formula 1 of the present invention is used as a pharmaceutical, it may additionally contain one or more active ingredients exhibiting the same or similar functions. For example, known ingredients for skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement may be included. When additional skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement components are included, the composition of the present invention provides skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-oxidation Inflammation, moisturizing, whitening, and skin texture improvement effects 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 of Formula 1. .

In addition, the pharmaceutical composition for skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement of the present invention may further include a pharmaceutically acceptable carrier.

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

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

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient in the pharmaceutical composition of the present invention, for example, starch, calcium carbonate, 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.

In the present invention, the 'skin regeneration effect' refers to the recovery of skin tissue against damage caused by external and internal skin causes. The damage caused by the external cause may include ultraviolet rays, external contaminants, wounds, trauma, and the like, and the damage caused by the internal cause may include stress.

In the present invention, the 'wrinkle improvement effect' refers to suppressing or inhibiting the formation of wrinkles on the skin, or alleviating wrinkles that have already been created.

In the present invention, the 'elasticity enhancing effect' refers to an increase in elasticity of the skin, suppressing or inhibiting the loss of skin elasticity, or alleviating already reduced elasticity.

In the present invention, the term 'atopic dermatitis improving effect' refers to preventing or treating skin diseases such as atopy and xeroderma, and refers to suppressing, inhibiting, or alleviating the symptoms of atopic dermatitis.

In the present invention, the term 'antioxidant effect' refers to the reduction of cells by highly reactive free radicals or reactive oxygen species (ROS) according to intracellular metabolism or oxidative stress caused by the influence of ultraviolet rays. It refers to inhibiting oxidation, and includes reducing damage to cells caused by the removal of free radicals or reactive oxygen species.

In the present invention, the term 'anti-inflammatory effect' refers to suppressing inflammation, and the inflammation is one of the defense reactions of living tissues to certain stimuli, which causes tissue deterioration, circulatory disorder and exudation, and tissue proliferation. refers to complex lesions. More specifically, inflammation is part of innate immunity, and as in other animals, innate immunity in humans recognizes cell surface patterns that are specific to pathogens. Phagocytes recognize cells with such surfaces as non-self and attack the pathogen. If a pathogen breaks through the body's physical barrier, an inflammatory response occurs. The inflammatory response is a non-specific defense action that creates a hostile environment for microorganisms invading the wound. In the inflammatory response, when a wound or an external infectious agent enters the body, white blood cells in charge of the early stage immune response flock to express cytokines. Therefore, the expression level of intracellular cytokines is an indicator of activation of the inflammatory response. Examples of skin diseases related to inflammation include atopic dermatitis, psoriasis, erythematous diseases triggered by radiation, chemicals, burns, etc., acid burns, bullous dermatosis, lichenoid type diseases, itching due to allergies, seborrheic eczema, rosacea, pemphigus vulgaris, exudative erythema multiforme, erythema nodosum, balanitis, vulvitis, inflammatory hair loss such as alopecia areata, cutaneous T-cell lymphoma, etc., but are not limited thereto.

In the present invention, the 'moisturizing effect' refers to inhibiting or suppressing the decrease in skin moisture or increasing the moisture content of the skin to smooth the skin surface and impart gloss.

In the present invention, the 'whitening effect' refers to not only brightening the skin tone by inhibiting the synthesis of melanin pigment, but also improving skin hyperpigmentation such as spots or freckles caused by ultraviolet rays, hormones or heredity.

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 pharmaceutical composition of the present invention, when containing an effective amount of the compound of Formula 1, has a desirable skin regeneration effect, wrinkle improvement effect, elasticity enhancement effect, atopy improvement effect, antioxidant effect, anti-inflammatory effect, moisturizing effect, whitening effect, and skin texture can provide an improvement effect. In the present invention, the term 'effective amount' means to promote regeneration of damaged skin, improve wrinkles, improve elasticity, improve skin dryness such as atopy, inhibit or alleviate cell oxidation, or reduce inflammation. It refers to the amount of a compound capable of inhibiting, improving skin texture, or exhibiting a moisturizing effect or a whitening effect. The effective amount of the compound of 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 the compound stays on the skin. For example, when the composition is commercialized as a pharmaceutical product, it may contain the compound of Formula 1 at a higher concentration than when the composition is 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 of Formula 1, and 1 to 100 mg/kg per day. 6 doses may be administered.

The pharmaceutical 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.

The present invention can also be provided in the form of an external skin formulation for skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement containing the compound of Formula 1 as an active ingredient.

When the compound of Formula 1 is used as an external skin preparation, it may additionally 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, and a surfactant. , water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles, or external preparations for skin It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients used as In addition, the components may be introduced in an amount generally used in the field of skin science.

When the compound of Formula 1 is provided as a formulation for external application to the skin, it may have formulations such as, but not limited to, ointments, patches, gels, creams, or sprays.

The present invention may also provide a cosmetic formulation for skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement containing the compound of Formula 1 as an active ingredient.

When the compound of Formula 1 is used as a cosmetic, the cosmetic product containing the compound of Formula 1 as an active ingredient may be prepared in the form of a general emulsified formulation or 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 of 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, and water. , ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, 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.

The compound of Formula 1 is a relatively high concentration of the compound of Formula 1 in the case of wash-off type cosmetics such as make-up removers and detergents in which active ingredients stay on the skin for a short period of time when commercialized as cosmetics. will be able to include On the other hand, in the case of leave-on type cosmetics such as lotion, lotion, cream, essence, etc. in which active ingredients stay on the skin for a long time, the compound of Formula 1 is used at a lower concentration than wash-off type cosmetics. It would be okay to include it. Although not limited thereto, in one embodiment of the present invention, the composition may contain 0.0001% to 10% by weight (preferably 0.0001% to 1% by weight) of the compound of Formula 1 based on the total weight of the composition. can 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 enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement effects cannot be expected. However, if it is included in an amount exceeding 10% by weight, unwanted reactions such as allergies may occur or there may be problems with skin safety, so this is to prevent this.

The present invention also relates to a health food for skin regeneration, wrinkle improvement, elasticity promotion, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and skin texture improvement containing the compound of Formula 1.

In the present specification, 'health food' refers to a food prepared by adding the compound of Formula 1 to food materials such as beverages, teas, spices, chewing gum, confectionery, etc., or encapsulated, powdered, or suspended. It means that it brings about a specific effect, but unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using food as a raw material.

Since the health food of the present invention obtained in this way can be consumed on a daily basis, high skin regeneration, wrinkle improvement, elasticity promotion, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening, and skin texture improvement effects can be expected. useful.

When the compound of Formula 1 is used as a food additive, the compound of 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.

The health beverage composition of the present invention may contain various flavoring agents or natural carbohydrates as additional components, like 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, the health food of the present invention includes 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 , carbonation agents used in carbonated beverages, and the like. In addition, the health food of the present invention 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 of 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 term 'stem cell activation promoting effect' refers to including the stem cell proliferation promoting effect and/or stem cell nature maintenance effect.

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. Through the activity of these stem cells, various phenomena of skin aging can be improved [Non-Patent Document 7], and in this regard, in the present invention, skin regeneration, wrinkle improvement, elasticity enhancement, atopy improvement, antioxidant, anti-inflammatory, moisturizing, whitening and The skin texture improvement effect was confirmed.

Therefore, the present invention can provide a cosmetic composition comprising the composition for promoting the stem cell activity. These cosmetic formulations are the same as those described in the description of cosmetic formulations containing the compound of Formula 1 above.

Hereinafter, the present invention will be described in detail by examples. However, the following examples are only to illustrate the present invention, and the content of the present invention is not limited to the following examples.

Reference Example 1: Material Information of Neoandrographolide

[Formula 1]

CAS No.: 27215-14-1

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

Reference Example 2: Cultivation of skin stem cells in serum-free medium conditions

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. Thereafter, the culture medium was removed through a suction tube, and then the medium components were removed using a PBS solution (GibcoBRL), and 20 μg/mL of the compound of Formula 2 was treated in CNT-57 medium without BPE, followed by 5% CO Incubated for 72 hours at ₂ and 37 ℃ conditions.

Experimental Example 1: Skin stem cell proliferation promotion effect through CCK-8 evaluation method

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.

After treating the cells with a CCK-8 solution (1/10 of the medium volume) at 37° C. for 2 hours, 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

Proliferative effect of skin stem cells Additive sample density Cell proliferation rate (%) compared to the control group Compound of Formula 1 20 μg/mL 109% control group - 100%

As can be seen from the results of Table 1, the skin stem cells in the medium conditions treated with the compound of Formula 1 of the present invention exhibited an excellent proliferation promoting effect.

Experimental Example 2: Checking the effect of maintaining stemness of skin stem cells

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 20 μg/mL 1.26 control group - 1.0

As can be seen from the results in Table 2, the medium conditions treated with the compound of Formula 1 of the present invention promote the expression of p63 in skin stem cells, resulting in an excellent stem cell property maintenance effect.

Example 1: Collagen synthesis promoting effect

The compound of Formula 1 was added to the culture medium of human-derived fibroblasts, and the effect of promoting collagen synthesis at the cellular level was tested. The measurement of biosynthesized collagen was quantified 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-derived fibroblasts (7 x 10 ⁴ cells/cm ² ) together with vitamin C and a control (no addition) to a final concentration of 10 μg/ml and 20 μg/ml, respectively. After culturing for 1 day, the culture medium was taken and the degree of collagen biosynthesis at each concentration was measured at 450 nm using a spectrophotometer using the PICP EIA Kit. Collagen biosynthetic performance was calculated as an increase rate relative to the control group, and the results are summarized in Table 3 below.

Collagen synthesis promotion effect according to concentration (repeat number = 3) added sample Concentration applied (μg/ml) Collagen synthesis increase rate (%) compared to the control group Compound of Formula 1 10 µg/ml 39.2% Compound of Formula 1 20 µg/ml 56.3% vitamin C 50 µg/ml 30.6%

As a result, as can be seen from the results in Table 3, the compound of Formula 1 of the present invention has excellent collagen synthesis ability with respect to human-derived fibroblasts, and is generally less concentrated than the case of applying vitamin C known to have collagen synthesis ability. It can be seen that a better collagen synthesis effect can be obtained.

Example 2: Whitening effect - confirmation of melanin production inhibitory effect

The compound of Formula 1 was added to the culture medium of mouse melanoma cells (B-16 mouse melanoma cells) to test the whitening effect at the cellular level (Lotan R., Lotan D. Cancer Res. 40:3345-3350, 1980 ).

Prior to the experiment, toxicity was evaluated for melanoma cells of mice, and whitening evaluation was performed by selecting a non-toxic concentration.

Experiments were conducted by setting the final concentration of the compound of Formula 1 to 10 μg/ml and 20 μg/ml in the culture medium, and arbutin, a control group, was added to the medium to be 200 μg/ml, and each B-16 melanoma cell was treated with 3 cultured for a day.

Thereafter, the cells were treated with trypsin, detached from the culture vessel, centrifuged, and then melanin was extracted. The detached cells were boiled for 10 minutes by adding 1 ml of sodium hydroxide solution (1N) to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to measure the amount of melanin produced.

The amount of melanin was measured by a method of expressing the absorbance per unit cell number (10 ⁶ cell), and the amount of melanin produced relative to the control group was calculated as an inhibition rate (%), and the results are summarized in Table 4 below.

Effect of inhibiting melanin production at the cellular level according to the concentration (Number of repetitions = 3) sample Inhibition rate (%) Control (no additives) - Control 1: Arbutin (200 μg/ml) 30.8 Compound of Formula 1 (20 μg/ml) 46.0 Compound of Formula 1 (10 μg/ml) 24.2

As can be seen from the results in Table 4, it can be seen that the compound of Formula 1 has a superior ability to inhibit melanin production against cultured mouse melanoma cells compared to Arbutin, a known whitening substance.

Example 3: Antioxidant effect - free radical scavenging rate

In order to confirm the antioxidant activity of the compound of Formula 1, the free radical scavenging activity was measured. Free radical scavenging activity was measured using DPPH. DPPH was purchased from Sigma Co., Ltd (USA) and used. First, a standard DPPH ethanol solution of 1.5 mM (0.06 mg/ml) was made. In addition, ethanol was added to the compound of Formula 1 and ascorbic acid, an antioxidant, as a reference material, respectively, to prepare samples at concentrations of 50 μg/ml, 25 μg/ml, 12.5 μg/ml, 6.25 μg/ml, and 3.125 μg/ml. . Then, the sample and the standard DPPH solution were added in the same ratio, stirred well, reacted at 37 ° C. for 30 minutes, and absorbance was measured at 520 nm. At this time, ethanol was added instead of the sample as a control. For the free radical scavenging ability, IC ₅₀ , which is a half maximal inhibitory concentration (median value of inhibition), was obtained, and the results are shown in Table 4 below. IC ₅₀ is the concentration of ascorbic acid and the compound of Formula 1 required to remove 50% of the free radicals in the no-additive control group, and is a general method of expressing free radical scavenging activity.

Free radical scavenging rate (IC ₅₀ ) sample Free radical scavenging rate (ug/ml) ascorbic acid 5.2 Compound of Formula 1 4.1

As can be seen from the results of Table 5, it can be seen that the compound of Formula 1 has an antioxidant effect because it shows high activity compared to ascorbic acid, which is a known antioxidant.

Example 4: Anti-inflammatory effect-NO production inhibitory effect

In order to confirm the anti-inflammatory effect and skin trouble alleviation effect of the compound of Formula 1, nitric oxide (NO) formation inhibition test was performed by the GRIESS method using the RAW264.7 cell line (ATCC number: CRL-2278).

Specifically, RAW264.7 cells, which are mouse macrophages, were subcultured several times, placed in a 24-well plate so that 3×10 ⁵ per well, and cultured for 24 hours. Subsequently, the cell medium was replaced with a diluted compound of Formula 1 at the concentration shown in Table 6 below. At this time, 20 μg/ml of L-NMMA (L-NG-Monomethylarginine), an NO-production inhibitor, was treated as a positive control and incubated for 30 minutes, and 1 μg of LPS (Lipopolysaccharide) was treated as a stimulus for 24 hours. cultured for a while. 100 μl of the supernatant was transferred to a 96-well plate, 100 μl of the GRIESS solution was added and reacted at room temperature for 10 minutes, and the NO inhibitory effect of compound 1 was determined by measuring the absorbance at 540 nm. Table 6 shows.

NO production inhibitory effect sample NO production inhibition rate (%) L-NMMA (positive control) 41.53 Compound of Formula 1 (0.1%) 38.32 Compound of Formula 1 (1%) 43.24

As can be seen from the results of Table 6, it can be seen that the compound of formula 1 has the same level of NO production inhibition ability as L-NMMA, a known anti-inflammatory substance.

Example 5: Verification of PPAR alpha activation promoting effect

In order to confirm the effect of the compound of Formula 1 on promoting PPAR alpha activation, the following experiment was performed using the compound of Formula 1. C2C12 cells (ATCC CRL-1772), a mouse-derived myoblast cell line, were subcultured in DMEM (Dulbeco's Modified Eagle's Medium) medium containing 10% fetal calf serum. The vectors used here include: 1) yeast transcription factor GAL4-DBD (DNA Binding Domain) and human PPAR alpha LBD (Ligand Binding Domain) encoding Ser ₁₆₇ to Tyr ₄₆₈ in the SV40 promoter of the pZEO vector (Invitrogen); A vector containing a DNA fragment (Genebank information, NM 005036), 2) a vector in which the GAL4 response sequence was inserted into multiple restriction enzyme recognition sites of the pGL3 vector (Promega) expressing Luciferase, and 3) a trans A vector expressing β-galactosidase was used as a transfection internal control.

The cultured cells were plated on a 24-well plate at a concentration of 4×10 ⁴ , cultured for 12 hours, and 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×PBS, and cells lysed with 1× reporter lysis buffer, followed by luciferase assay kit (Promega) and Luciferase activity was measured using a β-galactosidase assay kit (Promega). That is, PPAR alpha activity was measured as 'luciferase activity/β-galactose activity'.

As a positive control in this experiment, Wy-14,643 (Calbiochem), which is known to be the most potent of PPAR alpha ligands, was used, and as a negative control, 0.05% of DMSO used to dissolve the sample was used.

According to the above experimental method, C2C12 cells were treated with the compound of Formula 1 to measure the activity of PPAR alpha according to the concentration change, and the results are shown in Table 5 below. In Table 7 below, the numerical value of PPAR alpha activity means the percentage compared to the negative control group (DMSO 0.05%).

Activity of PPAR alpha sample PPAR alpha activity (%) DMSO (0.05%) 100 Wy-14,643 (0.5 μM) 280 Wy-14,643 (1 μM) 935 Compound of Formula 1 (0.05%) 712 Compound of Formula 1 (0.5%) 950

As shown in the results of Table 7, it was confirmed that the compound of Formula 1 exhibits very strong PPAR alpha activity when compared to the positive control, which is a purified compound.

Example 6: Filaggrin Expression Promotion Effect

The compound of Formula 1 was added to the culture medium of human keratinocyte HaCaT cells at 5 μg/ml and 10 μg/ml, respectively, and cultured for 1 day. Cell RNA was isolated, cDNA was synthesized, and Taqman staining solution Real-time PCR was performed with RNA concentration was normalized to S16 ribosomal RNA.

Effect of filaggrin expression according to concentration (number of repetitions = 3) Additive sample Increased fold of filaggrin compared to the control group Control (no additives) 1.00 Compound of Formula 1 (5 μg/ml) 30.4 Compound of Formula 1 (10 μg/ml) 54.0

As can be seen from the results of Table 8, the compound of Formula 1 has the ability to promote filaggrin expression in human keratinocyte HaCaT cells.

Example 7: Efficacy for improving keratin exfoliation (turn-over)

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.

After depositing a 1.5% solution of DHA (Dihydroxyacetone, Sigma Aldrich, USA) on the test site of 20 women aged 20 to 50 by occlusive patching for 8 hours, 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 in the deposition area, the higher the keratin exfoliation improvement effect.

The results are shown in Table 9 below.

skin brightening effect division 4 days after application 8 days after application 12 days after application Improvement rate (%) 1.29 4.52 11.28

As can be seen in Table 9, it was found that there was an effect of improving keratin exfoliation when the nutritional cream of the formulation example according to the present invention was used.

Formulation Example 1: Preparation of pharmaceutical formulation

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 external 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 (13)

delete delete delete delete delete delete delete delete A cosmetic composition for skin regeneration by promoting stem cell activity comprising a compound represented by Formula 1 below as an active ingredient:
[Formula 1]

According to claim 9,
The stem cell activity is a cosmetic composition for skin regeneration according to the promotion of stem cell activity, characterized in that the stem cell proliferation promotion or stem cell maintenance.
Skin external preparation for treating skin wounds according to the promotion of stem cell activity comprising a compound represented by Formula 1 as an active ingredient:
[Formula 1]

According to claim 11,
The stem cell activity is a skin external agent for treating skin wounds according to the promotion of stem cell activity, characterized by the promotion of stem cell proliferation or maintenance of stem cell nature.
A pharmaceutical composition for treating skin wounds by promoting stem cell activity comprising a compound represented by Formula 1 below as an active ingredient:
[Formula 1]