KR20210115316A - Composition for alleviating skin barrier damage comprising glyasperin d - Google Patents

Abstract

The present invention relates to a composition for alleviating skin barrier damage comprising glyasperin D or a stereoisomer, a salt, a hydrate or a solvate thereof as an active ingredient. The composition for alleviating skin barrier damage suppresses the activity of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), thereby exhibiting an effect of alleviating skin barrier damage caused by external stress such as UV rays, and the like.

Description

Composition for alleviating skin barrier damage comprising gliasperin D {COMPOSITION FOR ALLEVIATING SKIN BARRIER DAMAGE COMPRISING GLYASPERIN D}

The present specification relates to a composition for alleviating damage to the skin barrier.

The skin is the outermost organ of the human body and plays a role in protecting the human body from various external stimuli. Among the constituent layers of the skin, the epidermis plays a role in preventing the evaporation of moisture inside the human body. The epidermis is divided into stratum corneum, granular layer, stratum corneum, and basal layer in order from the outside.

When the skin is exposed to stress caused by environmental pollution, especially UV rays, the homeostasis of the skin barrier is broken, the skin becomes dry and the surface becomes rough, and the skin loses its moisture and looks lifeless.

Recently, studies on damage to the skin barrier caused by UV exposure are being actively conducted. Among them, research on cortisol, a key factor in stress control, is attracting attention. As cortisol increases by UV rays, KRT1 and KRT10, which are components of the skin barrier, decrease, causing damage to the skin barrier, which has been clinically proven.

11ß-HSD1 (11ß-hydroxysteroid dehydrogenase type 1) plays an important role in the increase of cortisol by UV exposure. 11ß-HSD1 is an enzyme that converts inactive cortisone to active cortisol, and is present in the epidermis and dermis. Therefore, it is necessary to develop a substance that inhibits the activity of 11ß-HSD1 to alleviate damage to the skin barrier.

Korean Patent Publication No. 10-2019-0003165

In one aspect, the present invention is to provide a composition for alleviating damage to the skin barrier.

In one aspect, the present invention provides a composition for alleviating skin barrier damage comprising gliasperin D or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient.

In an exemplary embodiment, the concentration of gliasperin D or a stereoisomer, salt, hydrate or solvate thereof in the composition may be 1 to 15 μM.

In an exemplary embodiment, the gliasperin D or a stereoisomer, salt, hydrate or solvate thereof may be administered at a dosage of 0.37 to 6 mg/kg/day.

In an exemplary embodiment, the skin barrier damage may be caused by ultraviolet rays.

In an exemplary embodiment, the active ingredient may inhibit cortisol production.

In an exemplary embodiment, the active ingredient may inhibit the activity of 11ß-HSD1 (11ß-hydroxysteroid dehydrogenase type 1).

In an exemplary embodiment, the composition may be a composition for external application to the skin.

In an exemplary embodiment, the composition may be a food, pharmaceutical or cosmetic composition.

In one aspect, the composition according to the present invention is excellent in alleviating damage to the skin barrier without side effects.

In one aspect, the composition according to the present invention is capable of inhibiting cortisol production.

In one aspect, the composition according to the present invention can inhibit the activity of 11ß-HSD1 (11ß-hydroxysteroid dehydrogenase type 1).

1 is a graph showing the cytotoxicity according to the concentration of gliaspearin D.
2 is a graph showing the effect of reducing cortisol production according to the treatment of gliaspearin D.
3 is a graph comparing the cortisol production reduction effect of gliaspearin D and glycyrrhizin.

Hereinafter, the present invention will be described in detail.

In one aspect, the present invention provides a composition for alleviating skin barrier damage comprising Glyasperin D or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient.

In one embodiment, the gliasperin D is 4-[(3R)-5,7-dimethoxy-6-(3-methylbut-2-enyl)-3, which may be represented by Formula 1 below; 4-dihydro-2H-chromen-3-yl]benzene-1,3-diol (4-[(3R)-5,7-dimethoxy-6-(3-methylbut-2-enyl)-3,4 -dihydro-2H-chromen-3-yl]benzene-1,3-diol).

[Formula 1]

In one embodiment, the concentration of gliasperin D or a stereoisomer, salt, hydrate or solvate thereof in the composition may be 1 to 15 μM. When the concentration of gliasperin D or a stereoisomer, salt, hydrate or solvate thereof is less than 1 μM, it is difficult to exhibit the effect according to the present invention, and when it exceeds 15 μM, skin irritation may occur. Specifically, the concentration of gliasperin D or a stereoisomer, salt, hydrate or solvate thereof in the composition is 1 μM or more, 1.2 μM or more, 1.4 μM or more, 1.8 μM or more, 2 μM or more, 2.2 μM or more, 2.4 At least 15 μM, at least 2.6 μM, at least 2.8 μM, at least 3 μM, at least 3.2 μM, at least 3.5 μM, at least 4 μM, at least 4.5 μM, at least 5 μM, at least 5.2 μM, at least 5.4 μM, or at least 5.5 μM or less, 14.7 µM or less, 14.5 µM or less, 14.3 µM or less, 14 µM or less, 13.7 µM or less, 13.5 µM or less, 13.3 µM or less, 13 µM or less, 12.7 µM or less, 12.5 µM or less, 12.3 µM or less, 12 µM or less, 11.7 µM or less, 11.5 µM or less, 11.3 µM or less, 11 µM or less, 10.7 µM or less, 10.5 µM or less, 10.3 µM or less, 10 µM or less, 9.5 µM or less, 9 µM or less, 8.5 µM or less, 8 µM or less, 7.5 µM or less or less, or 7 μM or less.

As used herein, "stereoisomer" includes optical isomers, e.g., essentially pure enantiomers, essentially pure diastereomers, or mixtures thereof.

As used herein, "essentially pure", for example, when used in reference to enantiomers or diastereomers, contains at least about 90%, preferably about 95% of the specific compound exemplified by enantiomers or diastereomers. % or more, more preferably about 97% or more or about 98% or more, even more preferably about 99% or more, even more preferably about 99.5% or more (w/w).

As used herein, "salt" refers to a salt according to an aspect of the present invention that is acceptable in medicine, cosmetics and food and has the desired activity of the parent compound. The salts are formed by (1) inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-Toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2,2,2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert -acid addition salts formed with organic acids such as butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and muconic acid; or (2) salts formed when an acidic proton present in the parent compound is substituted. In addition, the salt may be a pharmaceutically acceptable salt.

As used herein, "pharmaceutically acceptable" means avoiding significant toxic effects when used in conventional medicinal dosages, thereby obtaining approval from the government or equivalent regulatory body for use in animals, more specifically humans. available, approved, or listed in the Pharmacopoeia or recognized as other common pharmacopeias.

As used herein, the term “hydrate” refers to a compound to which water is bonded, and is a broad concept including inclusion compounds that do not have a chemical bonding force between water and the compound.

As used herein, the term “solvate” refers to a higher-order compound formed between a molecule or ion of a solute and a molecule or ion of a solvent.

As used herein, "active ingredient" refers to a component that can exhibit the desired activity alone or can exhibit activity together with a carrier that does not have the activity itself.

In one embodiment, the damage to the skin barrier may be induced by physical or chemical stimulation or stress, and specifically may be induced by ultraviolet rays. The ultraviolet rays may include ultraviolet A (UVA) and ultraviolet B (UVB), preferably ultraviolet B (UVB).

In one embodiment, the active ingredient may inhibit the production of cortisol.

In one embodiment, the active ingredient may inhibit the activity of 11ß-HSD1 (11ß-hydroxysteroid dehydrogenase type 1). The 11ß-HSD1 is an enzyme present between the epidermis and the dermis, and as it inhibits the activity of 11ß-HSD1, it inhibits the conversion of cortisone to cortisol, thereby alleviating damage to the skin barrier.

In one embodiment, the route of administration of the composition is not limited, but may preferably be transdermally or externally applied to the skin.

In one embodiment, the gliasperin D or a stereoisomer, salt, hydrate or solvate thereof by administration of the composition may be administered at a dosage of 0.37 to 6 mg/kg/day. When the dosage of gliasperin D or a stereoisomer, salt, hydrate or solvate thereof by administration of the composition is less than 0.37 mg/kg/day, it may be difficult to exhibit the skin barrier damage alleviation effect, and 6 mg/kg/day Excessive amounts may cause skin irritation. Specifically, the dosage of gliasperin D or a stereoisomer, salt, hydrate or solvate thereof by the administration of the composition is 0.37 mg/kg/day or more, 0.38 mg/kg/day or more, 0.39 mg/kg/day or more. ≥0.4 mg/kg/day, ≥0.41 mg/kg/day, ≥0.42 mg/kg/day, ≥0.43 mg/kg/day, ≥0.44 mg/kg/day, ≥0.45 mg/kg/day , 0.5 mg/kg/day or more, 0.55 mg/kg/day or more, 0.6 mg/kg/day or more, 0.65 mg/kg/day or more, 0.7 mg/kg/day or more, 0.8 mg/kg/day or more, 0.9 mg/kg/day or more, 1 mg/kg/day or more, 1.1 mg/kg/day or more, 1.2 mg/kg/day or more, 1.3 mg/kg/day or more, 1.5 mg/kg/day or more, 1.7 mg/ ≥ kg/day, ≥ 2 mg/kg/day, or ≥ 2.2 mg/kg/day and ≤ 6 mg/kg/day, ≤ 5.9 mg/kg/day, ≤ 5.7 mg/kg/day, 5.5 mg/kg /day or less, 5.3 mg/kg/day or less, 5 mg/kg/day or less, 4.9 mg/kg/day or less, 4.7 mg/kg/day or less, 4.5 mg/kg/day or less, 4.3 mg/kg/day or less no more than 4 mg/kg/day, no more than 3.95 mg/kg/day, no more than 3.9 mg/kg/day, no more than 3.85 mg/kg/day, no more than 3.8 mg/kg/day, no more than 3.75 mg/kg/day, 3.7 mg/kg/day or less, 3.65 mg/kg/day or less, 3.6 mg/kg/day or less, 3.55 mg/kg/day or less, 3.5 mg/kg/day or less, 3.4 mg/kg/day or less, 3.3 mg /kg/day or less, 3.2 mg/kg/day or less, 3.1 mg/kg/day or less, or 3 mg/kg/day or less.

In one embodiment, the composition may be a cosmetic composition. The cosmetic composition is, for example, softening lotion, astringent lotion, nourishing lotion, nourishing cream, massage cream, eye cream, eye essence, essence, cleansing cream, cleansing lotion, cleansing foam, cleansing water, pack, powder, body lotion , body cream, body essence, body cleaner, hair dye, shampoo, conditioner, hair dressing, hair conditioner, ointment, gel, cream, patch, spray, powder, and skin adhesion type, but are not limited thereto.

In addition, in each formulation, other components other than the above-mentioned essential components can be suitably selected and formulated by those skilled in the art without difficulty depending on the type or purpose of use of other external preparations.

The cosmetic composition may be provided in any formulation suitable for topical application. For example, it may be provided in the form of a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, a suspension, a solid, a gel, a powder, a paste, a microneedle, a foam, or an aerosol composition. have. Compositions of such formulations can be prepared according to conventional methods in the art.

The cosmetic composition according to the present specification may further include functional additives and components included in general cosmetic compositions in addition to the compounds of the present specification. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and seaweed extract. The cosmetic composition according to the present specification may include other ingredients that can give a synergistic effect to the main effect, preferably within a range that does not impair the main effect. In addition, the cosmetic composition according to the present specification may further include a moisturizing agent, an emollient, a surfactant, a UV absorber, a preservative, a bactericide, an antioxidant, a pH adjuster, an organic and inorganic pigment, a fragrance, a cooling agent or a limiting agent. The blending amount of the component can be easily selected by those skilled in the art within the range that does not impair the purpose and effect of the present specification, and the blending amount may be 0.001 to 10% by weight, specifically 0.01 to 3% by weight, based on the total weight of the composition. have.

In one embodiment, the composition may be a food composition. The formulation of the food composition is not particularly limited, but, for example, may be formulated in tablets, granules, pills, powders, liquids such as drinks, caramel, gels, bars, tea bags, and the like. In addition to the active ingredient, the food composition of each formulation can be appropriately selected by those skilled in the art without difficulty depending on the formulation or purpose of use in addition to the active ingredient, and a synergistic effect may occur when applied simultaneously with other raw materials.

The food composition according to one embodiment includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, colorants and enhancers (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and its salts. salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages, and the like. In addition, the food compositions according to an embodiment may include natural fruit juice and pulp for the production of fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The proportion of these additives is not so important, but is generally included in the range of 0 to about 50 parts by weight per 100 parts by weight of the composition according to an embodiment.

In one embodiment, the composition may be a pharmaceutical composition. The pharmaceutical composition may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, or the like. Formulations for oral administration may be tablets, pills, soft and hard capsules, granules, powders, fine granules, liquids, emulsions, or pellets, but are limited thereto it is not Formulations for parenteral administration may be solutions, suspensions, emulsions, gels, injections, drops, suppositories, patches, or sprays, but is not limited thereto. The formulation can be easily prepared according to conventional methods in the art, and surfactants, excipients, wettable powders, emulsification accelerators, suspending agents, salts or buffers for osmotic pressure control, coloring agents, spices, stabilizers, preservatives, preservatives or Other commercially available adjuvants may be further included.

Hereinafter, the present invention will be described in more detail through examples and the like. These examples are only for illustrating the present invention, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not to be construed as being limited by these examples.

[Experimental Example 1] Keratinocyte culture

The keratinocytes (Human normal epidermal keratinocytes, Lonza社, USA) a human-derived cells were cultured in a CO ₂ incubator _{(CO 2 incubator) 37 ℃,} 5% CO 2 conditions. The cell culture medium followed Lonza's instructions. KGM-2 Bullet kit CC-4152 (KGM TM-2 Bullet kit, CC-4152) (ingredient: Bovine pituitary extract (BPE)), human epidermal growth in 500 ml of KBM-2 (KBMTM-2, CC-3103) medium Human epidermal growth factor (hEGF), Insulin, Hydrocortisone, Transferrin, Epinephrine, and Gentamycin Suflate + Amphofericin-B (Gentamycin Suflate + Amphofericin-B: GA) -1000)) added KGM-2 Bullet Kit CC-3107 (KGM TM-2 Bullet Kit, CC-3107) was used. The cultured keratinocytes were seeded in a 6-well plate at 15,000 per well, and cultured using a medium not added with hydrocortisone.

[Experimental Example 2] Cytotoxicity measurement

In order to measure the cytotoxicity of glycerin D, the keratinocytes cultured in Experimental Example 1 were treated with glycerin D for 24 hours at different concentrations, the culture medium was removed from the wells, and CCK8 reagent (Donjindo Co., Ltd.) , CK04) was diluted 1/10 in DMEM medium and treated for 3 hours, then absorbance was measured at 450 nm, and the results are shown in FIG. 1 .

As can be seen in FIG. 1 , it was found that the cell viability was about 76% in 20 μM glycerin D, indicating cytotoxicity.

[Experimental Example 3] Cortisol production amount measurement

In order to confirm the cortisol reduction effect of gliasperin ^{D, after UVB (16mJ/cm 2} ) was irradiated to the keratinocytes cultured in Experimental Example 1, cortisone 10 μM and gliasperin D were added by concentration (1 μM). , 5 μM, 10 μM) and cultured for 2 days. The amount of cortisol produced in the culture medium in which the gliasperin D-treated keratinocytes were cultured was measured using a cortisol ELISA kit (R&D Systems, USA) according to the manufacturer's protocol, and the results are shown in FIG. 2 .

As can be seen in FIG. 2 , it was found that cortisol production by UV exposure was reduced by treatment with gliasperin D. In particular, in the case of the group in which the concentration of gliasperin D was 10 μM, it was confirmed that the amount of cortisol production was reduced by about half or more compared to the group not treated with gliasperin D.

In addition, the cortisol production amount of 10 μM glycyrrhizin was measured in the same manner as above, and the results were compared with glycyrrhizin D 10 μM, and the results are shown in FIG. 3 .

As can be seen in FIG. 3 , it was confirmed that gliasperin D had a superior effect on reducing cortisol production by UV exposure than glycyrrhizin at the same concentration.

[Formulation Example 1] Liquid ampoule

A liquid ampoule was prepared in a conventional manner according to the composition shown in Table 1 below.

ingredient content (wt%) Gliasperin D 0.01 arginine 0.50 Green Tea Polyphenols 0.05 Indigestible maltodextrin 1.00 vitamin C 0.10 citric acid 0.10 Spices 0.05 Purified water remaining amount Sum 100.00

[Formulation Example 2] Soap

Soap was prepared in a conventional manner according to the composition shown in Table 2 below.

ingredient content (wt%) Gliasperin D 0.50 titanium dioxide 0.20 polyethylene glycol 0.80 glycerin 0.50 Ethylenediaminetetraacetic acid 0.05 salt 1.00 pigment 0.20 soapy scent 0.20 soap base remaining amount Sum 100.00

[Formulation Example 3] Lotion

A lotion was prepared in a conventional manner according to the composition shown in Table 3 below.

ingredient content (wt%) Gliasperin D 0.60 L-ascorbic acid-2-magnesium phosphate salt 1.00 Collagen 1.00 sodium citrate 0.10 citric acid 0.05 Licorice Extract 0.20 1,3-butylene glycol 3.00 Purified water remaining amount Sum 100.00

[Formulation Example 4] Cream

Creams were prepared in a conventional manner according to the composition shown in Table 4 below.

ingredient content (wt%) Gliasperin D 0.60 Polyethylene glycol monostearate 2.00 Self-emulsifying glycerin monostearate 5.00 cetyl alcohol 4.00 squalene 6.00 tri2-glyceryl ethyl henate 6.00 sphingoglycolipids 1.00 1,3-butylene glycol 7.00 Purified water remaining amount Sum 100.00

[Formulation Example 5] Pack

A pack was prepared in a conventional manner according to the composition shown in Table 5 below.

ingredient content (wt%) Gliasperin D 0.60 polyvinyl alcohol 13.00 L-ascorbic acid-2-magnesium phosphate salt 1.00 Lauroylhydroxyproline 1.00 Collagen 2.00 1,3-butylene glycol 3.00 ethanol 5.00 Purified water remaining amount Sum 100.00

[Formulation Example 6] Cosmetic liquid formulation

According to the composition shown in Table 6 below, a cosmetic liquid formulation was prepared by a conventional method.

ingredient content (wt%) Gliasperin D 0.50 Hydroxyethylene Cellulose 12.00 xanthan gum 2.00 1,3-butylene glycol 6.00 glycerin 4.00 Sodium Hyaluronate 5.00 Purified water remaining amount Sum 100.00

[Formulation Example 7] Soft capsules

Gliasperin D 120mg, L-carnitine 160mg, soybean oil 320mg, palm oil 2mg, hydrogenated vegetable oil 8mg, yellow wax 4mg and lecithin 6mg were mixed and filled into 1 capsule according to a conventional method to prepare a soft capsule.

[Formulation Example 8] Tablet

Gliasperin D 130mg, galactooligosaccharide 500mg, lactose 80mg and maltose 220mg were mixed and granulated using a fluidized bed dryer, 6 mg of sugar ester was added thereto, and the tablet was compressed with a tableting machine to prepare tablets.

[Formulation Example 9] Granules

Gliasperin D 120 mg, anhydrous crystalline glucose 250 mg, and starch 550 mg were mixed, formed into granules using a fluidized bed granulator, and then filled in a bag to prepare granules.

[Formulation Example 10] Drink formulation

에서 4~5 초간 살균하여 드링크제 음료를 제조하였다. After mixing 100 mg of gliasperin D, 10 g of glucose, 0.6 g of citric acid, and 25 g of liquid oligosaccharide, 500 ml of purified water is added, and 200 ml of each bottle is filled. 130 after filling the bottle

It was sterilized for 4 to 5 seconds to prepare a drink beverage.

Claims (8)

A composition for alleviating skin barrier damage comprising Glyasperin D or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient. According to claim 1,
The composition of claim 1, wherein the concentration of gliasperin D or a stereoisomer, salt, hydrate or solvate thereof in the composition is 1 to 15 μM. According to claim 1,
The composition, wherein the gliasperin D or a stereoisomer, salt, hydrate or solvate thereof is administered at a dosage of 0.37 to 6 mg/kg/day. According to claim 1,
The skin barrier damage is caused by ultraviolet rays, the composition. According to claim 1,
The active ingredient is to inhibit cortisol production, the composition. According to claim 1,
The active ingredient is to inhibit the activity of 11ß-HSD1 (11ß-hydroxysteroid dehydrogenase type 1), the composition. 7. The method according to any one of claims 1 to 6,
The composition is a composition for external application to the skin. 7. The method according to any one of claims 1 to 6,
The composition is a food, pharmaceutical or cosmetic composition, composition.

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