TECHNICAL FIELD

The present invention relates to a cosmetic composition for alleviating skin barrier dysfunction, a pharmaceutical composition for preventing or treating skin barrier dysfunction, a quasi-drug composition for preventing or alleviating skin barrier dysfunction, a method for alleviating skin barrier dysfunction, and a method for preventing or treating skin barrier dysfunction.

BACKGROUND ART

The epidermis is tissue that is always in contact with the external environment. It mainly protects the human body from external physical damage and chemical substances, prevents bacteria, fungi, and viruses from invading the skin, and has a role as a protective barrier to prevent moisture loss. The epidermis is composed of the stratum basale, stratum spinosum, stratum granulosum, and stratum corneum, which is the outermost layer. Although the stratum corneum is shed and falls off gradually, the keratinocytes located in the basement membrane divide asymmetrically and differentiate in the direction toward the outside of the epidermis to maintain the structural and functional homeostasis of the epidermis. In recent years, the increase in the exposure to strong ultraviolet rays due to environmental pollution, etc., as well as inflammatory reactions due to fine dust, attenuation of the barrier function, and the increase of moisture loss in the skin resulting therefrom have led to the acceleration of skin aging and the increase in skin damage and incidence rate of related diseases (KR 10-2015-0043026 A).

Autophagy is a mechanism by which the damaged substances are removed and energy is regenerated by degradation of old or damaged intracellular substances and organelles when the intracellular stress factor is excessively generated or the intracellular energy source is depleted, and autophagic activity has been observed in the epidermis as well as in several epithelial tissues. According to various reports, autophagy is essential for maintaining the homeostasis of the epidermis and exerting appropriate skin barrier function. In particular, it plays an important role in a viral infection of the epidermis, inflammatory reaction due to ultraviolet rays, melanosome delivery, and differentiation of keratinocytes, and also has a crucial role in removing mitochondria, Golgi apparatus, vesicles, nuclei, etc. when the keratinocytes finally differentiate into the stratum corneum. As aging progresses or accelerates, it has been reported in various recent studies that intracellular autophagic activity decreases rapidly. If autophagy is suppressed, aged mitochondria or proteins with denatured structures accumulate excessively in the cell, leading to an increase in intracellular free radicals and oxidative stress, thereby increasing cell death and accelerating aging.

Light Chain 3 (LC3) are proteins whose amount increases during autophagy. They undergo a post-translational transformation process during the autophagy process. After translation into Pro-LC3, they produce cytoplasmic LC3-I through cleavage of the 22ndamino acid at the carboxy terminal by autophagy-related protein 4 (atg4), and during autophagy, LC3-I is converted to LC3-II, while being lipidated by phosphatidylethanolamine (PE) through a ubiquitin-like system involving atg3 and atg7, and consequently, LC3 is linked to autophagosomes.

Mammalian target of rapamycin (mTOR) is a ser/thr kinase, which responds to changes in ATP and amino acids and is known to have a role in balancing the availability of nutrients and cell growth. In an environment where sufficient nutrients can be supplied, mTOR is phosphorylated through the class I PI3K/Akt signaling pathway and then transmits a positive signal to the p70S6 kinase, and is involved in the inactivation of 4E-BP1 (i.e., an eIF4E inhibitor) to translate specific mRNA groups, and also inhibits autophagy.

DISCLOSURE

Technical Problem

According to the present invention, in order to improve the barrier function by promoting epidermal differentiation through activation of autophagy, which is reduced by aging or external stimuli, an extensive search has been conducted starting from a library of single compounds derived from natural substances for those that promote autophagic activity of keratinocytes, and as a result, hydroxycinnamic acid, isoamyl acetate, and betaine have been found to be appropriate. Additionally, the present invention has been completed by confirming the efficacy of promoting autophagic activity and increasing the thickness of the epidermis in a 3D artificial skin model based on an in vitro experiment.

Technical Solution

One object of the present invention is to provide a cosmetic composition for alleviating skin barrier dysfunction, including one or more compounds selected from the group consisting of hydroxycinnamic acid, isoamyl acetate, and betaine, or an acceptable salt thereof, as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating skin barrier dysfunction, including one or more compounds selected from the group consisting of hydroxycinnamic acid, isoamyl acetate, and betaine, or a pharmaceutically acceptable salt thereof, as an active ingredient.

Still another object of the present invention is to provide a quasi-drug composition for preventing or alleviating skin barrier dysfunction, including one or more compounds selected from the group consisting of hydroxycinnamic acid, isoamyl acetate, and betaine, or a pharmaceutically acceptable salt thereof, as an active ingredient.

Still another object of the present invention is to provide a method for alleviating skin barrier dysfunction, including applying the cosmetic composition to a subject.

Still another object of the present invention is to provide a method for preventing or treating skin barrier dysfunction, including administering the pharmaceutical composition to a subject excluding humans, or applying the pharmaceutical composition to the skin of a subject excluding humans.

Advantageous Effects

According to the present invention, hydroxycinnamic acid, isoamyl acetate, or betaine promotes autophagic activity independently of the mTOR pathway in keratinocytes and accelerates the turnover of the epidermis to increase the thickness of the epidermis, thereby improving the barrier function and preventing the senescence-induced attenuation of the epidermis.

