WO2021080129A1 - Composition for strengthening skin barrier and alleviating atopic dermatitis, having hydrangenol or phyllodulcin as active ingredient - Google Patents

Abstract

The present invention relates to a composition for strengthening the skin barrier and alleviating atopic dermatitis, having hydrangenol or phyllodulcin as an active ingredient. The composition having hydrangenol or phyllodulcin or a pharmaceutically acceptable salt thereof as an active ingredient, according to one aspect, has the effect of strengthening the skin barrier and can be effectively used for preventing, alleviating, or treating atopic dermatitis.

Description

Composition for strengthening skin barrier and improving atopic dermatitis using hydragenol or filodulcin as active ingredients

It relates to a composition for strengthening skin barrier and improving atopic dermatitis, using hydrangenol or filodulcin as an active ingredient.

The upper layer of the outermost epidermis of the skin forms a skin barrier with keratinocytes. The skin barrier is the most important primary defense against toxic substances, microorganisms, mechanical irritation, and ultraviolet rays. It provides an environment in which to perform. Therefore, when the skin barrier is damaged, the skin becomes dry and rough, and is easily exposed to harmful substances, which may cause problematic skin such as atopic dermatitis, contact dermatitis, psoriasis, and dry aged skin.

Pilagrine, an important component of the skin barrier, is a substance that helps keratin fibrous tissues of keratinocytes clump together. It has the function of binding between keratinocytes and secreting lipids between cells. Recently, natural moisturizing factors within keratinocytes are made as decomposition products of filaggrin, and interest in filaggrin is increasing as the results of studies in which atopic dermatitis and dry skin lack filaggrin and chromosomal mutations have been found. (J Allergy Clin Immunol, 2009, 122, 689-693). When filaggrin is insufficient, the bond between keratinocytes in the stratum corneum is weakened, so that external stimuli are easily transmitted to the inside of the skin, and moisturizing ingredients become insufficient, which can exacerbate various skin diseases such as atopic dermatitis.

Atopic dermatitis is a recurrent chronic skin disease, which occurs frequently in infancy, but persists even in adults or may develop newly in adulthood, and its prevalence is increasing recently (Kor J Pharmacogn 2012, 43, 59-65). The cause of atopic dermatitis has not been clearly identified yet, but it has been found to be mainly associated with many genetic factors and immune response. In particular, Th1/Th2 imbalance due to an increase in the number of Th2 cells compared to Th1 cells is known as an important factor. .

The immune system, which is a defense mechanism against external invasion of the human body, is centered on the activation of T cells.Inflammation accompanying atopic dermatitis is caused by excessive immune cell action and mass production of inflammatory cytokines and reactive oxygen species, resulting in damage to surrounding tissues. It is the result. Among various cytokines, TARC/CCL17 (Thymus & activation-related chemokine/Chemokine (CC motif) ligand 17) is a representative chemokine that acts on Th2 cells, and its concentration has been reported to increase significantly in atopic dermatitis patients and animal models. TARC and MDC/CCL22 (Macrophage-derived chemokine/ Chemokine (CC motif) when TNF-α (Tumor necrosis factor-alpha) or IFN-γ (Interferon-gamma) was treated with human keratinocytes (HaCaT) in an in vitro experiment. ) ligand 22) is expressed in a large amount, which suggests that a substance capable of inhibiting this expression can be used as a therapeutic agent for atopic dermatitis.

Plant-derived materials are excellent in terms of safety and have been used for a long time. In particular, in the case of Korea, the development of functional materials mainly made of plants and herbal ingredients used in the private sector or used in oriental medicine is being actively carried out.

Hydrangea is also known as nectar, and is a family of Panuigwidae. It is also grown in Korea as a native plant or around temples. In addition, in the “raw materials that can be used in food” notified by the Ministry of Food and Drug Safety, the leaf part is specified as an edible part with item number A 107400 (「Food Standards and Standards」 (No. 2018-60, 2018.08. .16.)).

Hydrangenol is a representative component found in Hydrangea (Japanese Patent Application Publication No. JP-0029934), its molecular weight is 256.25 g/mol, and the IUPAC name is 8-hydroxy-3- (4-hydroxyphenyl)-3, It is 4-dihydroisochromen-1-one. Also its derivatives include (-)-hydrangenol 4'-O-glucoside and (+)-hydrangenol 4'-O-glucoside.

Phyllodulcin (C16H14O5; (R)-3,4-dihydroxy-3-(4-methoxy-3-hydroxyphenyl) isocoumarine) is an ingredient found in hydrangea. Expressed by

However, studies on a composition for strengthening skin barrier and improving atopic dermatitis using hydrangenol or Phyllodulcin derived from Hydrangea extract as an active ingredient have not been conducted yet. Therefore, the present inventors conducted a direct study on the efficacy of these substances.

One aspect is to provide a cosmetic composition for preventing or improving atopic dermatitis using Hydrangenol, Phyllodulcin, or an acceptable salt thereof as an active ingredient.

Another aspect is to provide a composition for external application for skin for the prevention or improvement of atopic dermatitis, using hydrangenol, filodulcin, or an acceptable salt thereof as an active ingredient.

Another aspect is to provide a pharmaceutical composition for the prevention or treatment of atopic dermatitis using hydrangenol, filodulcin, or an acceptable salt thereof as an active ingredient.

Another aspect is to provide a health functional food composition for preventing or improving atopic dermatitis using hydrangenol, filodulcin, or an acceptable salt thereof as an active ingredient.

Another aspect is to provide a cosmetic composition for strengthening the skin barrier using hydrangenol, phyllodulcin, or an acceptable salt thereof as an active ingredient.

Another aspect is to provide a health functional food composition for strengthening the skin barrier, using hydrangenol, phyllodulcin, or an acceptable salt thereof as an active ingredient.

Another aspect is to provide a method for preventing, ameliorating or treating atopic dermatitis comprising administering to an individual in need thereof an effective amount of hydrangenol, filodulcin, or a pharmaceutically acceptable salt thereof.

Another aspect is to provide a use of hydragenol, filodulcin, or a pharmaceutically acceptable salt thereof for use in the preparation of a composition for preventing, ameliorating or treating atopic dermatitis.

One aspect provides a cosmetic composition for preventing or improving atopic dermatitis using Hydrangenol, Phyllodulcin, or an acceptable salt thereof as an active ingredient.

In one embodiment, the hydrangenol or phyllodulcin may be isolated from an extract of the genus Hydrangea (Hydrangea macrophylla or Hydrangea serrata).

The hydroxy is jenol (Hydrangenol) or pillow dulsin (Phyllodulcin) may be purified natural products isolated from the genus Hydrangea (Hydrangea) in the hydrangea and (Hydrangea). Hydrangea genus ( Hydrangea ) may be one or more selected from the group consisting of whole, woody roots, stems, branches, leaves, seeds or fruits, preferably leaves may be used.

The hydrangea in (Hydrangea) extract can be extracted also in the hot-water extract used to extract the natural plant in the art, solvent extraction, distillation extraction, supercritical extraction, etc. any extraction method, preferably, pure water, organic solvent or their It can be extracted with a mixed solvent of.

The hydrangea extract may be extracted using water, alcohol, for example, C1-C6 alcohol, for example, C1-C4 alcohol, or a mixture thereof as a solvent. The C1-C6 alcohol may be methanol, ethanol, propanol, isopropanol, 1,3-propanediol, butanol, pentanol, hexanol, and the like. The solvent may be, for example, a mixture of water and alcohol, that is, an aqueous alcohol solution. The alcohol concentration of the aqueous alcohol solution is 1 to 99.5 (v/v)%, for example, 10 to 99.5 (v/v)%, 1 to 70 (v/v)%, 1 to 40 (v/v)%, 5 to 25 (v/v)%, 7 to 20 (v/v)%, 5 to 25 (v/v)%, or 10 to 20 (v/v)%. The aqueous alcohol solution may be an aqueous ethanol solution.

The extraction is 3 to 10 times (vol/weight) times, for example, 3 to 7 times (volume/weight) times, 3 to 5 times (volume/weight) times, 5 to 10 times (volume/weight) times the hydrangea genus. It may include adding weight) times, or 4 to 10 times (volume/weight) times. For example, it may include adding 3 to 10 L of the extraction solvent to 1 kg of the material derived from the hydrangea genus ( Hydrangea).

The extraction is performed by warmed liquid extraction, pressurized liquid extraction (PLE), microwave assisted extraction (MAE), subcritical extraction (SE), or a combination thereof. Can be. The subcritical extraction may be subcritical water extraction (SWE). Subcritical water extraction is also referred to as superheated water extraction or pressurized hot water extraction (PHWE). The heated liquid extraction may be reflux extraction.

The extraction is 4 to 70 ℃, for example, 4 to 50 ℃, 4 to 40 ℃, 4 to 30 ℃, 10 to 70 ℃, 15 to 70 ℃, 20 to 70 ℃, 4 to 50 ℃, 10 to 50 It may be performed at ℃, 4 to 40 ℃, 4 to 30 ℃, 10 to 40 ℃, 10 to 35 ℃, or 10 to 30 ℃. The extraction time may vary depending on the selected temperature, for example, 1 hour to 2 months, for example, 1 hour to 1 month, 1 hour to 15 days, 1 hour to 10 days, 1 hour to 5 days, 1 hour to 3 days. , 1 hour to 2 days, 1 hour to 1 day, 5 hours to 1 month, 5 hours to 15 days, 5 hours to 10 days, 5 hours to 5 days, 5 hours to 3 days, 5 hours to 2 days, 5 It may be time to 1 day, 10 hours to 1 month, 10 hours to 15 days, 10 hours to 10 days, 10 hours to 5 days, 10 hours to 3 days, or 10 hours to 2 days. The extraction may include mixing the whole hydrangea genus, a part thereof, or a material derived therefrom in the solvent and leaving it for a certain period of time. The standing may include suitable agitation. The extraction may be repeated one or more times, for example, 1 to 5 times.

The extraction may be performed by separating plant residues and extracts by known methods such as filtration. The extraction may also include removing the solvent from the obtained extract by known methods such as concentration under reduced pressure. The extraction may also include preparing a dried extract by drying the obtained extract, such as lyophilization.

The hydragenol or filodulcin is 0.0001% to 99.0% by weight, for example, 0.01% to 60%, 0.01% to 40%, 0.01% to 30%, 0.01% by weight based on the total weight of the composition. Weight% to 20% by weight, 0.01% to 10% by weight, 0.01% to 5% by weight, 0.05% to 60% by weight, 0.05% to 40% by weight, 0.05% to 30% by weight, 0.05% by weight To 20% by weight, 0.05% to 10% by weight, 0.05% to 5% by weight, 0.1% to 60% by weight, 0.1% to 40% by weight, 0.1% to 30% by weight, 0.1% to 20% by weight It may be included in wt%, 0.1 wt% to 10 wt%, or 0.1 wt% to 5 wt%.

The term "atopic dermatitis" is one of the allergic diseases and is a skin disease accompanied by symptoms such as itching, dry skin, increased skin thickness, and characteristic eczema.

The term “prevention” refers to partially or completely delaying or preventing the onset or recurrence of a disease, disorder, or ancillary symptoms thereof, preventing the acquisition or reacquisition of a disease or disorder, or the risk of acquiring a disease or disorder. Says how to reduce it. For example, the prevention refers to any action that suppresses or delays the occurrence of obesity, or obesity-related diseases, disorders, or symptoms by administration of the composition according to the present invention.

The term “improvement” may refer to any action that at least reduces the severity of a parameter related to treatment or a parameter related to treatment or remission of a condition.

In one embodiment, the hydragenol or phyllodulcin may be represented by the following formula (1).

[Formula 1]

In Formula 1, R1 is any one selected from the group consisting of hydrogen and a hydroxyl group; R2 may be any one selected from the group consisting of hydrogen, a hydroxyl group and an ether. In one embodiment of the present invention, in hydrangenol, R1 is hydrogen, R2 is a hydroxyl group, and phyllodulcin, R1 is a hydroxyl group, and R2 is a methoxy group.

In one embodiment, the hydrangenol or filodulcin may increase the expression of one or more selected from the group consisting of filaggrin, involucrin, and loricrin.

The filaggrin, involukrin, and loliclean may be genes or proteins that play an important role in the formation of the stratum corneum. Increasing the expression of the gene or protein may mean that it strengthens the skin barrier and alleviates atopic dermatitis.

In one embodiment, the hydragenol or phyllodulcin may be one that reduces one or more expressions from the group consisting of COX-2, IL-6, and TARC/CCL17.

The COX-2, IL-6 and TARC/CCL17 may be genes or proteins expressed in an inflammatory response. Reducing the expression of the gene or protein may mean that it strengthens the skin barrier and alleviates atopic dermatitis.

The cosmetic composition is composed of softening lotion, nourishing lotion, nourishing cream, moisture cream, massage cream, essence, ampoule, gel, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, powder, gel, lotion, and ointment. It may have a formulation selected from the group. The cosmetic composition may additionally include one or more cosmetically acceptable carriers formulated in general skin cosmetics, and as common ingredients, for example, oil, water, surfactants, moisturizers, lower alcohols, thickeners, chelates Agents, colors, preservatives, flavors, and the like may be appropriately blended, but are not limited thereto.

The cosmetic composition may include other additives such as excipients, carriers, etc. in addition to hydrangenol, pilodulcin, or an acceptable salt thereof, and it may be possible to apply and blend as many ordinary ingredients as necessary.

In addition, the cosmetic composition includes medicinal ingredients such as higher fatty acids and vitamins, and sunscreens, antioxidants (butylhydroxyanisole, propyl gallic acid, lysorbic acid, tocopheryl acetate, butylated hydroxytoluene, etc.), if necessary. ), preservatives (methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinylurea, chlorphenesin, etc.), colorants, pH adjusters (triethanolamine, citric acid, citric acid, sodium citrate, malic acid, sodium malate) , Pmalic acid, sodium fmarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, etc.), moisturizing agents (glycerin, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin, beta Ingredients such as phosphorus, glyceres-26, methylgluces-20, etc.), and lubricants may be further added.

In addition, the cosmetic composition further includes a substance capable of auxiliaryly providing essential nutrients to the skin, and preferably, a natural fragrance, a cosmetic fragrance, or an herbal medicine may be included, but may contain an adjuvant, which is not limited thereto.

Another aspect provides a composition for external application for skin for the prevention or improvement of atopic dermatitis, using hydrangenol, filodulcin, or an acceptable salt thereof as an active ingredient.

In one embodiment, the hydrangenol or phyllodulcin may be isolated from an extract of the genus Hydrangea (Hydrangea macrophylla or Hydrangea serrata).

The external preparation for skin may be a cream, a gel, an ointment, a skin emulsifier, a skin suspension, a transdermal delivery patch, a drug-containing bandage, a lotion, or a combination thereof.

The above skin external preparations are ingredients commonly used in external preparations for skin such as cosmetics and pharmaceuticals, such as aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances. , Colorants, various skin nutrients, etc. can be appropriately blended as needed.

The external preparations for the skin include metal sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, bellapamil, licorice extract, glavidine, and caline. Hot water extract of fruit, various herbal medicines, drugs such as tocopherol acetate, glytilithic acid, tranexamic acid and derivatives or salts thereof, vitamin C, ascorbic acid magnesium phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, Sugars such as trehalose can also be appropriately blended.

Another aspect provides a pharmaceutical composition for preventing or treating atopic dermatitis, using hydrangenol, filodulcin, or an acceptable salt thereof as an active ingredient.

In one embodiment, the hydrangenol or filodulcin may increase the expression of one or more selected from the group consisting of filaggrin, involucrin, and loliclean.

In one embodiment, the hydragenol or phyllodulcin may be one that reduces one or more expressions from the group consisting of COX-2, IL-6, and TARC/CCL17.

The term “pharmaceutical composition” can refer to a molecule or compound that imparts several beneficial effects upon administration to a subject. The beneficial effect is to enable diagnostic decisions; Improvement of a disease, symptom, disorder or condition; Reducing or preventing the onset of a disease, symptom, disorder or condition; And in general the response of a disease, symptom, disorder or condition.

The pharmaceutical composition can be administered parenterally during clinical administration and can be used in the form of a general pharmaceutical formulation. Parenteral administration may mean administration through a route other than oral administration such as rectal, intravenous, peritoneal, muscle, arterial, transdermal, nasal, inhalation, ocular and subcutaneous. When using the pharmaceutical composition of the present invention as a pharmaceutical, it may further contain one or more active ingredients exhibiting the same or similar functions.

Types of pharmaceutical active ingredients that can deliver the active ingredient into an individual include anticancer agents, contrast agents (dyes), hormone agents, anti-hormonal agents, vitamin agents, calcium agents, inorganic agents, saccharides, organic acid agents, protein amino acid preparations, detoxification agents, enzymes. Preparations, metabolic preparations, diabetes combination preparations, tissue revitalization preparations, chlorophyll preparations, pigment preparations, tumor medicines, tumor treatments, radiopharmaceuticals, tissue cell diagnostics, tissue cell treatments, antibiotic preparations, antiviral agents, complex antibiotics, chemistry Therapeutic agents, vaccines, toxins, toxoids, antitoxins, leptospira serum, blood products, biological agents, analgesics, immunogenic molecules, antihistamines, allergy medications, non-specific immunogenic agents, anesthetics, stimulants, psychotropic agents, low molecular weight compounds, nucleic acids, Aptamers, antisense nucleic acids, oligonucleotides, peptides, siRNAs, micro RNAs, and the like.

When formulating the pharmaceutical composition, it is prepared using diluents or excipients such as generally used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for the suppository, Witepsol, Macrogol, Tween 61, cacao butter, liurinji, glycerogelatin, and the like may be used.

The pharmaceutical composition may be used by mixing with various carriers (Carrier) allowed as a drug such as physiological saline or an organic solvent, and carbohydrates such as glucose, sucrose or dextran, ascorbic acid (Ascorbic acid) to increase stability or absorption. Antioxidants such as acid) or glutathione, chelating agents, small molecule proteins or other stabilizers may be used as pharmaceuticals.

In addition, the pharmaceutically effective amount and effective dosage of the pharmaceutical composition may vary depending on the method of formulating the pharmaceutical composition, the mode of administration, the time of administration, and/or the route of administration. In addition, the type and degree of reaction to be achieved by the administration of the pharmaceutical composition, the type of the subject to be administered, age, weight, general health condition, symptoms or degree of disease, sex, diet, excretion, simultaneous or It may be varied according to various factors, including components of drugs and other compositions used together at this time, and similar factors well known in the field of medicine. Those of ordinary skill in the art can easily determine and prescribe an effective dosage for the desired treatment. The administration of the pharmaceutical composition according to the present invention may be administered once a day, or may be administered several times. Therefore, the above dosage does not limit the scope of the present invention in any way. The dosage of the pharmaceutical composition may be 1 ug/kg/day to 1,OOO mg/kg/day per day.

Another aspect provides a health functional food composition for preventing or improving atopic dermatitis using hydrangenol, filodulcin, or an acceptable salt thereof as an active ingredient.

In one embodiment, the health functional food is one having a formulation selected from the group consisting of powders, granules, tablets, capsules, pills, gels, jellies, suspensions, emulsions, syrups, tea bags, leached tea, and health beverages. I can.

In addition to the active ingredients, the health food includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavors and natural flavoring agents, coloring agents and heavy weight agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid, and It may contain salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like.

Another aspect provides a cosmetic composition for strengthening the skin barrier using hydrangenol, phyllodulcin, or an acceptable salt thereof as an active ingredient.

The skin barrier strengthening is psoriasis, contact dermatitis, eczematous dermatitis, photodermatitis, seborrheic dermatitis, herpes dermatitis, lichen planus, lichen sclerosis, pyoderma gangrene, pemphigus, blistering epidermis. It may mean relieving detachment, systemic sclerosis or leprosy.

Another aspect provides a health functional food composition for strengthening the skin barrier, using hydrangenol, phyllodulcin, or an acceptable salt thereof as an active ingredient.

Another aspect provides a method of preventing, ameliorating or treating atopic dermatitis comprising administering to an individual in need thereof an effective amount of hydrangenol, filodulcin, or a pharmaceutically acceptable salt thereof.

The subject may be a mammal. The mammal may be a human, dog, cat, cow, goat, or pig.

The administration can be administered through any general route as long as it can reach the target tissue. For example, it may be administered through a route such as eye drop, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, transdermal patch administration, oral administration, intranasal administration, intrapulmonary administration, and rectal administration, Specifically, it may be administered as desired through the route of eye drop administration. The administration can be administered systemically or locally.

As used herein, “treatment” or “treating” or “relaxing” or “improving” are used interchangeably. These terms refer to a method of obtaining an advantageous or desired result, including, but not limited to, a therapeutic benefit and/or a prophylactic benefit. A therapeutic benefit refers to any therapeutically significant improvement or effect thereon of one or more diseases, disorders or symptoms under treatment. In a prophylactic benefit, the composition may be administered to a subject at risk of developing a particular disease, condition, or symptom, or to a subject reporting one or more physiological symptoms of the disease, even if the disease, condition, or symptom is not yet present.

The term “effective amount” or “therapeutically effective amount” refers to an amount of an agent sufficient to produce an advantageous or desired result. The therapeutically effective amount may vary according to one or more of the subject and condition to be treated, the weight and age of the subject, the severity of the condition, the mode of administration, and the like, which can be easily determined by a person skilled in the art. Further, the term applies to the capacity to provide an image for detection by any of the imaging methods described herein. The particular dose may vary depending on one or more of the particular agent selected, the dosage regimen that follows, whether it is administered in combination with other compounds, the timing of administration, the tissue being imaged, and the body delivery system that carries it.

The administration is 0.1 mg to 1,000 mg per individual, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg per individual, of hydragenol, filodulcin, or a pharmaceutically acceptable salt thereof, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg may be administered. . However, the dosage may be variously prescribed depending on factors such as the formulation method, the mode of administration, the patient's age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate, and response sensitivity. In consideration of these factors, the dosage can be appropriately adjusted. The number of administration can be once a day or two or more times within the range of clinically acceptable side effects, and the administration site can be administered at one or two or more locations, and a total of daily or at intervals of 2 to 5 days. The number of days of administration can be administered from 1 to 30 days per treatment. If necessary, the same treatment can be repeated after an appropriate time period. For non-human animals, the same dose per kg as human or, for example, the volume ratio (e.g., average value) of the target animal and human organs (heart, etc.) One amount can be administered.

Another aspect provides the use of hydrangenol, filodulcin, or a pharmaceutically acceptable salt thereof for use in the preparation of a composition for preventing, ameliorating or treating atopic dermatitis.

The terms and methods described for the above invention are applied equally to each of the inventions.

According to the composition comprising hydrangenol or phyllodulcin or an acceptable salt thereof according to an aspect as an active ingredient, the skin barrier is strengthened and there is an effect that can be usefully used in the prevention, improvement or treatment of atopic dermatitis.

Figure 1 is a scheme of isolation is hydroxy separated from the genus Hydrangea (Hydrangea) jenol (Hydrangenol).

2 is a MS (positive-ion mode) spectrum of Hydrangenol.

3 is a ¹ H-NMR spectrum of Hydrangenol.

4 is a ¹³ C-NMR spectrum of Hydrangenol.

5 is a DEPT NMR spectrum of Hydrangenol.

6 is an HSQC NMR spectrum of Hydrangenol.

7 is an HMBC NMR spectrum of Hydrangenol.

8 is an isolation scheme of Phyllodulcin isolated from Hydrangea.

9 is an MS (positive/negative-ion mode) spectrum of Phyllodulcin.

10 is a ¹ H-NMR spectrum of Phyllodulcin.

11 is a ¹³ C-NMR spectrum of Phyllodulcin.

12 is an HSQC NMR spectrum of Phyllodulcin.

13 is an HMBC NMR spectrum of Phyllodulcin.

FIG. 14 is a graph showing the expression level control of hydrangenol, filodulcin, or hydrangea genus extracts of pilagrin, involukrin, and loliclean.

15 is a graph showing an increase in the expression amount of pilagrin according to the concentration of hydrangenol in an animal experiment.

16 is a graph showing an increase in the expression level of involucrin according to the concentration of hydrangenol in an animal experiment.

17 is a graph showing the decrease in the amount of expression of COX-2 and IL-6 according to the concentration of hydrangenol in an animal experiment.

18 is a graph showing an increase in the expression amount of pilagrin according to the concentration of pilodulsin.

19 is a graph showing an increase in the expression level of lolyclean according to the concentration of pilodulcin.

Figure 20 is a graph showing the cell viability according to the concentration of hydrangenol, phyllodulcin or hydrangea genus extract.

21 is a graph showing the decrease in the expression amount of the TARC gene according to the concentration of hydrangenol and pilodulcin.

22 is a graph showing an increase in the expression amount of pilagrin according to the concentration of hydrangenol and pilodulsin.

It will be described in more detail through the following examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

Example 1: Preparation of hydrangea extract

Hydrangea (Hydrangea) extract of the composition of the present invention is prepared by the following process. First, dry hydrangea ( Hydrangea macrophylla or Hydrangea serrata ) leaves 20 kg of raw materials and 300 kg of purified water were placed in an extraction tank and extracted under reflux for 5 hours at 100°C. The extracted sample was filtered through a cartridge filter (10 um), concentrated under reduced pressure, and spray-dried to obtain a water-soluble powder.

Example 2: Hydrangea genus ( Hydrangea ) Preparation of Hydrangenol derived from extract

The extract powder obtained in Example 1 was subjected to gel filtration using Diaion HP-20. As the developing solvent, 2 L of a mixed solution of 30%, 50%, 70%, 100% methanol and CH2Cl2-MeOH (1:1, v/v) was used for each solvent fraction, and 5 small fractions (Fr.1~) Divided into 5). The small fraction Fr.4 was divided into 7 small fractions (Fr.4-1~7) using Sephadex LH-20 using methanol as a developing solvent, and the Fr.4-4 fraction was recrystallized from methanol to form an amorphous compound. 1 (hydrangenol) single substance was obtained purely.

In order to confirm the structure of Example 2, first, as a result of confirming ESIMS (positive-ion mode), it was found that m/z = 257 [M+H]+ (FIG. 2). In 1H-NMR (Fig. 3), the methine proton (H-3) at δH 5.50 and the methylene proton (H-4) at δH 3.30 and 3.06 are vicinal coupling to each other and the chemical shift value is C. It can be seen that it is a proton originating from the ring. H-2', 3'and H-6', 5'originating from the p-substituted benzene ring of the B-ring are ortho-coupled to each other and appear as doublet (J = 8.4 Hz), and H-2' and H-6 The peaks of'and the peaks of H-3' and H-5' were also ortho-coupled to each other and appeared as a doublet, indicating that they had a symmetric structure around the hydroxy group. In 1,2,3-trisubstituted benzene of A-ring, H-5 and hydrogen 7 are coupled with H-6 hydrogen, respectively, and H-5 and 7 hydrogen are ortho coupling, doublet, and H-6 proton are ortho and meta. It appeared as a double of doublets by coupling, and it was found that all peaks correspond to one hydrogen.

In 13C-NMR (FIG. 4), a total of 15 peaks including para-substituents appeared. The quarternary carbon at δC 172 is a peak originating from the carbonyl group, carbon 1 of the compound, and δC 116.9 (C-3', 5') and 129.6 (C-2', 6') are attributed to the para substituent of the aromatic ring. It is one peak, and the peaks at δC 36.1 and 83.1 can be expected to be caused by aliphatic carbon and oxygenated carbon, respectively. In addition, DEPT NMR (FIG. 5) confirmed 7 protonated carbons, and the peak at δC 36.1 was found to be a methylene group originating from C-4. In order to analyze their exact structure, 2D NMR was analyzed. The exact positions of the peaks were identified from HSQC (FIG. 6), and the location at which the substituent was bonded could be known from HMBC (FIG. 7). That is, the peak of δH 7.26 (2H, d, J = 8.4 Hz, H-2', 6') is correlated with the C-4 of δC 36.1, and the peaks of δH 3.06 and 3.30 resulting from H-4 are δC The peaks of 83.1 (C-3), 119.8 (C-5), 110.0 (C-9), and 142.2 (C-10) were correlated. By synthesizing the above results, it was confirmed that the material obtained in Example 2 was Hydrangenol.

2 is a MS (positive-ion mode) spectrum of Hydrangenol.

3 is a ¹ H-NMR spectrum of Hydrangenol.

4 is a ¹³ C-NMR spectrum of Hydrangenol.

5 is a DEPT NMR spectrum of Hydrangenol.

6 is an HSQC NMR spectrum of Hydrangenol.

7 is an HMBC NMR spectrum of Hydrangenol.

Example 3: Hydrangea genus ( Hydrangea ) Preparation of Phyllodulcin derived from extract

The extract powder obtained in Example 1 was subjected to gel filtration using Diaion HP-20. As the developing solvent, 2 L of a mixed solution of 30%, 50%, 70%, 100% methanol and CH2Cl2-MeOH (1:1, v/v) was used for each solvent fraction, and 5 small fractions (Fr.1~) Divided into 5). The small fraction Fr.4 was divided into 7 small fractions (Fr.4-1 to 7) using Sephadex LH-20 using methanol as a developing solvent, and the Fr.4-3 fraction was recrystallized from methanol to form an amorphous compound. 2 (phyllodulcin) single substance was obtained purely.

In order to confirm the structure of Example 3, first, as a result of confirming LC-MS (negative-ion mode), it was found that m/z = 285 [M-H]- (FIG. 9). In 1H-NMR (Fig. 10), the methine proton (H-3) at δH 5.65 and the methylene proton (H-4) at δH 3.34 and 3.16 are vicinal coupling to each other and the chemical shift value is C. It can be seen that it is a proton originating from the ring.

H-2' originating from the p-substituted benzene ring of the B-ring meta-couples with H-6' to form a doublet (J = 2.4 Hz, δH 6.95), and the H-6' peak is H-2', -3' peaks and mata, ortho coupling, respectively, appear as double of doublets (J = 2.4,8.4 Hz, δH 6.90), and H-5' is ortho-coupled to H-6' and doublet (J = 8.4 Hz) , δH 6.96), it was found that the structure was substituted with the ABX system. It was found that three singlet hydrogens, which are presumed to be methoxy, were identified at δH 3.91.

In 1,2,3-trisubstituted benzene of A-ring, H-5 and hydrogen 7 are coupled to H-6 hydrogen, respectively, and H-5 and 7 hydrogen are ortho coupling doublet, and H-6 proton is H-5. , It was found as triplets by ortho coupling with hydrogen No. 7, and all of them were found to be peaks corresponding to one hydrogen.

In 13C-NMR (FIG. 11), a total of 16 peaks including para-substituents appeared. The quarternary carbon at δC 169.3 is a peak from the carbonyl group, carbon 1 of the compound, and the carbon at δC 55.6 is a peak from the methoxy group, and the peaks at δC 33.6 and 80.2 are from aliphatic carbon and oxygenated carbon, respectively. Could be expected. In order to analyze their exact structure, 2D NMR was analyzed. The exact positions of the peaks were identified from HSQC (FIG. 12), and the position at which the substituent was bonded could be known from HMBC (FIG. 13). By synthesizing the above results, it was confirmed that the material obtained in Example 3 was phyllodulcin.

9 is an MS (positive/negative-ion mode) spectrum of Phyllodulcin.

10 is a ¹ H-NMR spectrum of Phyllodulcin.

11 is a ¹³ C-NMR spectrum of Phyllodulcin.

12 is an HSQC NMR spectrum of Phyllodulcin.

13 is an HMBC NMR spectrum of Phyllodulcin.

Experimental Example 1: Evaluation of changes in skin barrier-related gene expression level of hydrangenol, filodulcin or hydrangea extract

To confirm the skin barrier strengthening effect of Hydrangea macrophylla, HM, Hydrangea serrata, HS, Hydrangea serrata, HS For this purpose, human keratinocytes (HaCaT, (ATCC, USA)) were treated with a single concentration to confirm the change in the expression levels of filagreen, involukrin, and loliclean.

Specifically, HaCaT cells 2x10 ⁶ cells were dispensed with DMEM medium (Hyclone SH30243.01) to which 10% FBS was added to a 60 mm plate and stabilized for 24 hours. After removing the existing medium and culturing in serum starvation for 24 hours, 25 ug/ml of the extract obtained in Example 1 and 100 uM of the compounds of Examples 2 and 3 were treated. After culturing for 24 hours, the culture solution was removed and washed with PBS, and the cell pellet was recovered by treatment with Trypsin-EDTA. After that, RNA was extracted from the obtained cells using a Trizol reagent, and cDNA was synthesized from the RNA obtained using a cDNA synthesis kit (Bio-Rad), and this was used as a template. PCR) was carried out (LightCycler 96, Roche, Switzerland). The RT-PCR reaction was performed under conditions of 40 cycles of 95°C for 600 seconds pre-incubation followed by 95°C for 10 seconds, 60°C for 10 seconds, and 72°C for 10 seconds. The expression level of the gene was finally analyzed through correction for the β-actin gene.

gene Primer direction Primer sequence (5'→ 3') Sequence number Pillar Green Forward AGTGCACTCAGGGGGCTCACA One Reverse CCGGCTTGGCCGTAATGTGT 2 Involukrin Forward TTGGTCAGTGAAGCGATGAG 3 Reverse AGATCTGTCTGCAGGGCTGT 4 Lori Clean Forward TCATAAGAAACCCCGCTGAG 5 Reverse AAGGAAGGAGAGCCTGGAAG 6 COX-2 Forward CTCACACCACAGAAAGTTAAAAGAT 7 Reverse GCTACCACAGGCACATCACG 8 IL-6 Forward AAGCCAGAGCTGTGCAGATGAGTA 9 Reverse TGTCCTGCAGCCACTGGTTC 10 TARC/CCL17 Forward CTTCTCTGCAGCACATCC 11 Reverse AAGACCTCTCAAGGCTTTG 12 β-actin Forward CATGTACGTTGCTATCCAGGC 13 Reverse CTCCTTAATGTCACGCACGAT 14

qRT-PCR was performed using the oligomer shown in Table 1 as a primer. The primer set is specific for the filaggrin, involukrin and loliclean genes, and these are skin barrier-related genes. As shown in Figure 14, it was confirmed that hydrangenol (HY) and phyllodulcin (PHY) increased all of the skin barrier-related genes.

FIG. 14 is a graph showing the expression level control of hydrangenol, filodulcin, or hydrangea genus extracts of pilagrin, involukrin, and loliclean.

Experimental Example 2: Changes in skin barrier and inflammation-related gene expression levels of hydrangenol in vivo evaluation

In order to confirm the skin barrier strengthening and anti-inflammatory effect of the hydrangenol obtained in Example 2 above, after irradiating ultraviolet rays to a hairless mouse (HR-1), pilagrin, involukrin, COX-2 and IL-6 in the mouse epidermis It was confirmed the change in the expression amount of.

Specifically, hairless mice (SLC, Japan) three times a week for 7 weeks 60 mJ/cm2 (weeks 1 and 2), 120 mJ/cm2 (weeks 3 and 4), 180 mJ/cm2 (weeks 5 and 6), Ultraviolet rays of 240 mJ/cm2 (week 7) were irradiated. In addition, hydragenol 5, 10, 20, and 50 mg/kg were administered orally. After 7 weeks, the mice were sacrificed to remove the dorsal epidermis, RNA was extracted using a Trizol reagent, and cDNA was synthesized from the obtained RNA using a cDNA synthesis kit (Bio-Rad). Using the synthesized cDNA as a template, quantitative real time-PCR (qRT-PCR) was performed (LightCycler 96, Roche, Switzerland). The RT-PCR reaction was performed under the conditions of 40 cycles repeated at 95° C. 600 seconds pre-incubation followed by 95° C. 10 seconds, 60° C. 10 seconds, and 72° C. 10 seconds. The expression level of the gene was finally analyzed through correction for the β-actin gene. qRT-PCR was performed using the oligomer shown in Table 1 as a primer.

According to the results shown in Figs. 15 and 16, when ultraviolet rays are applied to the hairless mouse, the skin barrier collapses, resulting in a decrease in pillar green and involukrin. It was confirmed that hydrangenol significantly increased the expression levels of the two genes. Could (**p<0.01, ***p<0.001). In addition, as shown in FIG. 17, the expression levels of the inflammation-related genes COX-2 and IL-6, which were increased by UV irradiation, were decreased in a concentration-dependent manner (#p<0.05, ***p<0.001). .

These results indicate that the hydrangenol of Example 2 can be usefully used to improve atopic dermatitis through strengthening the skin barrier by increasing the expression level of genes involved in the skin barrier and reducing the expression levels of genes involved in inflammation. Means.

15 is a graph showing an increase in the expression amount of pilagrin according to the concentration of hydrangenol in an animal experiment.

16 is a graph showing an increase in the expression level of involucrin according to the concentration of hydrangenol in an animal experiment.

17 is a graph showing the decrease in the amount of expression of COX-2 and IL-6 according to the concentration of hydrangenol in an animal experiment.

Experimental Example 3: Evaluation of changes in the expression level of genes related to skin barrier of phyllodulcin

In order to confirm the effect of strengthening the skin barrier by pilodulcin obtained in Example 3, human keratinocytes (HaCaT) were treated with a single concentration to confirm the change in the expression levels of filaggrin and loliclean.

Specifically, HaCaT cells 2x10 ⁶ cells were dispensed with DMEM medium (Hyclone SH30243.01) to which 10% FBS was added to a 60 mm plate and stabilized for 24 hours. After removing the existing medium and incubating for 24 hours in serum starvation, the compounds obtained in Example 3 were treated with 1 and 10 100 uM, respectively. After culturing for 24 hours, the culture solution was removed and washed with PBS, and the cell pellet was recovered by treatment with Trypsin-EDTA. After that, RNA was extracted from the obtained cells using a Trizol reagent, cDNA was synthesized from the RNA obtained using a cDNA synthesis kit (Bio-Rad), and this was used as a template. -PCR) was carried out (LightCycler 96, Roche, Switzerland). The RT-PCR reaction was performed under the conditions of 40 cycles repeated at 95° C. 600 seconds pre-incubation followed by 95° C. 10 seconds, 60° C. 10 seconds, and 72° C. 10 seconds. The expression level of the gene was finally analyzed through correction for the β-actin gene. qRT-PCR was performed using the oligomer shown in Table 1 as a primer. As shown in FIGS. 18 and 19, it was confirmed that phyllodulcin significantly increased skin barrier-related genes according to the concentration (**p<0.01, ***p<0.001).

These results indicate that the phyllodulcin of Example 3 can be usefully used to improve atopic dermatitis through strengthening the skin barrier by increasing the expression level of genes involved in the skin barrier and reducing the expression levels of genes involved in inflammation. it means.

18 is a graph showing an increase in the expression amount of pilagrin according to the concentration of pilodulsin.

19 is a graph showing an increase in the expression level of lolyclean according to the concentration of pilodulcin.

Experimental Example 4: Evaluation of cytotoxicity of hydrangenol and filodulcin

In order to measure the cytotoxicity of hydrangenol and filodulcin obtained in Examples 2 and 3, human keratinocytes (HaCaT) cells were treated with TNF-α and IFN-γ to measure cell viability by MTT assay.

Specifically, human keratinocytes HaCaT cells 1×10 ⁴ cells were dispensed into each well of a 96-well plate in DMEM medium added with 10% FBS and stabilized for 24 hours. Remove the existing medium, treat 10 nM TNF-α and 10 nM IFN-γ with each concentration of hydrangenol and phyllodulcin, respectively, and incubate in serum starvation for 24 hours, and then MTT (3-(4,5 Cell viability was measured through -dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Finally, each cell was treated with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) solution (Sigma, USA) so that the concentration was 0.5 mg/ml, and for 4 hours. After incubation, the solution was completely removed and the plate dissolved in DMSO (dimethyl sulfoxide) was measured at absorbance of 540 nm.

As a result, it was confirmed that hydrangenol and phyllodulcin did not show cytotoxicity (FIG. 20).

As shown in FIG. 20, 100 uM of hydrangenol and phyllodulcin, which are concentrations that do not show cytotoxicity, were determined as the highest concentrations, and subsequent experiments were conducted.

Figure 20 is a graph showing the cell viability according to the concentration of hydrangenol, phyllodulcin or hydrangea genus extract.

Experimental Example 5: Evaluation of changes in gene expression level for confirming the effect of improving atopic dermatitis of hydrangenol and phyllodulcin

In order to confirm the atopic dermatitis improvement effect of hydrangenol and pilodulcin obtained in Examples 2 and 3 above, human keratinocytes (HaCaT) were treated with hydrangenol and pilodulcin to change the expression levels of TARC and pilagrin genes. Confirmed.

Specifically, HaCaT cells 4x10 ⁵ cells were dispensed with DMEM medium added with 10% FBS to a 6-well plate and stabilized for 24 hours. Existing medium was removed, 10 nM TNF-α and 10 nM IFN-γ were treated with hydragenol and phyllodulcin at respective concentrations, and then incubated for 6 hours under serum starvation. Thereafter, the culture solution was removed and washed with PBS, and the cell pellet was recovered by treatment with Trypsin-EDTA. After that, RNA was extracted from the obtained cells using a Trizol reagent, cDNA was synthesized from the RNA obtained using a cDNA synthesis kit (Bio-Rad), and this was used as a template. -PCR) was carried out (LightCycler 96, Roche, Switzerland). The RT-PCR reaction was performed under conditions of 40 cycles of 95°C for 600 seconds pre-incubation followed by 95°C for 10 seconds, 60°C for 10 seconds, and 72°C for 10 seconds. The expression level of the gene was finally analyzed through correction for the β-actin gene. qRT-PCR was performed using the oligomer shown in Table 1 as a primer.

As a result, as shown in Figs. 21 and 22, it was confirmed that hydrangenol and phyllodulcin inhibited the expression level of the TARC gene, which was increased when inducing atopic dermatitis, in a concentration-dependent manner, and, on the contrary, increased when inducing atopic dermatitis It was confirmed that the filaggrin gene was significantly increased according to the concentration (**p<0.01, ***p<0.001).

The above results indicate that hydrangenol and phyllodulcin derived from the hydrangea extract are effective for preventing, treating, and improving atopic dermatitis by strengthening the skin barrier.

21 is a graph showing the decrease in the expression amount of the TARC gene according to the concentration of hydrangenol and pilodulcin.

22 is a graph showing an increase in the expression amount of pilagrin according to the concentration of hydrangenol and pilodulsin.

Formulation Example 1: Preparation of tablets

In Examples 1, 2 or 3, according to a conventional tablet manufacturing method, the ingredients in Table 2 were mixed and tableted to prepare tablets.

Raw material name Unit weight (mg) Unit weight (mg) Example 1 300.0006 - Example 2 or 3 - 10.0006 Silicon dioxide 15.3000 15.3000 Magnesium stearate 10.8000 10.8000 Crystalline cellulose 509.4945 799.4945 Hydroxypropylmethylcellulose 29.0700 29.0700 Calcium carboxymethylcellulose 27.0000 27.0000 Glycerin fatty acid ester 0.6930 0.6930 Titanium dioxide 1.4697 1.4697 Red Guk Red Pigment 4.4082 4.4082 Powdered caramel color 1.7640 1.7640

Formulation Example 2: Preparation of capsules

For Examples 1, 2, or 3, according to a conventional capsule preparation method, the ingredients of Table 3 were mixed and filled into a gelatin capsule to prepare a soft capsule preparation.

Raw material name Unit weight (mg) Unit weight (mg) Example 1 50 - Example 2 or 3 - 2 Vitamin E 2.25 2.25 Vitamin C 2.25 2.25 palm oil 0.5 0.5 Hydrogenated vegetable oil 2 2 Yellow lead One One lecithin 2.25 2.25 Soft Capsule Filling Solution 387.75 387.75

Formulation Example 3: Preparation of liquid formulation

In Examples 1, 2, or 3, the ingredients in Table 4 were mixed according to a method for preparing a beverage suitable for preference, and then filled in an oversized bottle or pouch to prepare a liquid formulation.

Raw material name Unit weight (g) Unit weight (g) Example 1 2.5050 - Example 2 or 3 - 0.1000 Xanthan gum 0.0075 0.0075 Fructooligosaccharide solution 0.7500 0.7500 Coconut flower essence powder 1.0500 1.0500 Ssanghwa Concentrate 1.5000 1.5000 Red ginseng flavor 0.0450 0.0450 Purified water 9.1425 9.1425

Formulation Example 4: Preparation of Jelly

For Examples 1, 2, or 3, the ingredients of Table 5 were mixed according to the method for preparing a jelly suitable for preference, and then filled in a three-sided cloth to prepare a jelly.

Raw material name Unit weight (g) Unit weight (g) Example 1 2.0000 - Example 2 or 3 - 0.1000 Food Gel 0.3600 0.3600 Carrageenan 0.0600 0.0600 Calcium lactate 0.1000 0.1000 Sodium citrate 0.0600 0.0600 Complex Golden Extract 0.0200 0.0200 Enzyme treatment stevia 0.0440 0.0440 Fructooligosaccharide solution 5.0000 5.0000 Red grape concentrate 2.4000 2.4000 Purified water 13.9560 13.9560

Formulation Example 5: Preparation of nutritional cream

For Examples 1, 2 or 3, a nourishing cream was prepared in the composition of Table 6 below according to a conventional method.

Raw material content (%) content (%) Example 1 1.0 - Example 2 or 3 - 0.05 Cytosterol 4.0 4.0 Polyglyceryl 2-oleate 3.0 3.0 3.0 Ceteares-4 2.0 2.0 cholesterol 3.0 3.0 Dicetylphosphate 0.4 0.4 Concentrated glycerin 5.0 5.0 Sunflower Oil 22.0 22.0 Carboxyvinyl polymer 0.5 0.5 Triethanolamine 0.5 0.5 antiseptic a very small amount a very small amount Spices a very small amount a very small amount Purified water Balance Balance

The above composition ratio is generally formulated as a formulation example by mixing suitable ingredients, but the mixing ratio and raw materials may be arbitrarily changed as necessary.

Since the extract of the present invention is stable under the test conditions of all formulation examples, there is no problem in the stability of the formulation.

Claims (15)

Hydrangenol (Hydrangenol), phyllodulcin (Phyllodulcin), or a cosmetic composition for preventing or improving atopic dermatitis using a pharmaceutically acceptable salt thereof as an active ingredient. The cosmetic composition of claim 1, wherein the hydragenol or phyllodulcin is isolated from an extract of the genus Hydrangea (Hydrangea macrophylla or Hydrangea serrata). The cosmetic composition of claim 1, wherein the hydragenol or phyllodulcin is represented by the following formula (1). [Formula 1]

In Formula 1, R1 is any one selected from the group consisting of hydrogen and a hydroxyl group; R2 is any one selected from the group consisting of hydrogen, a hydroxyl group and an ether. The cosmetic composition of claim 1, wherein the hydragenol or phyllodulcin increases the expression of at least one selected from the group consisting of pilagrin, involukrin, and loliclean. The cosmetic composition of claim 1, wherein the hydragenol or phyllodulcin reduces the expression of one or more from the group consisting of COX-2, IL-6, and TARC/CCL17. Hydrangenol (Hydrangenol), phyllodulcin (Phyllodulcin), or a pharmaceutically acceptable salt thereof as an active ingredient atopic dermatitis prevention or improvement composition for external application for skin. The composition for external application for skin according to claim 6, wherein the hydrangenol or phyllodulcin is isolated from an extract of the genus Hydrangea (Hydrangea macrophylla or Hydrangea serrata). Hydrangenol (Hydrangenol), phyllodulcin (Phyllodulcin), or a pharmaceutical composition for the prevention or treatment of atopic dermatitis using a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutical composition of claim 8, wherein the hydragenol or phyllodulcin increases the expression of at least one selected from the group consisting of pilagrin, involucrin, and loliquerin. The pharmaceutical composition of claim 8, wherein the hydragenol or phyllodulcin reduces the expression of one or more from the group consisting of COX-2, IL-6 and TARC/CCL17. Hydrangenol (Hydrangenol), phyllodulcin (Phyllodulcin), or a pharmaceutically acceptable salt thereof as an active ingredient for preventing or improving atopic dermatitis health functional food composition. A cosmetic composition for strengthening the skin barrier using Hydrangenol, Phyllodulcin, or a pharmaceutically acceptable salt thereof as an active ingredient. Hydrangenol (Hydrangenol), phyllodulcin (Phyllodulcin), or a pharmaceutically acceptable salt thereof as an active ingredient for strengthening the skin barrier health functional food composition. A method of preventing, ameliorating or treating atopic dermatitis comprising administering to an individual in need thereof an effective amount of hydrangenol, filodulcin, or a pharmaceutically acceptable salt thereof. Use of hydragenol, filodulcin, or a pharmaceutically acceptable salt thereof in the preparation of a composition for preventing, ameliorating or treating atopic dermatitis.

Images