KR20180066392A - Composition for preventing or improving skin wrinkle comprising α-glucopyranosyloxy benzyl alcohol as active ingredient - Google Patents

Abstract

The present invention relates to a cosmetic composition for preventing or alleviating skin wrinkle, comprising α-glucopyranosyloxy benzyl alcohol as an active ingredient. The composition of the present invention increases expression of type I procollagen protein in human dermal fibroblast cells, inhibits expression of MMP-1, MMP-3, and MMP-9 protein, and effectively inhibits an AP-1 signaling system, an MAPK signaling system, and an NF-kB signaling system, thereby preventing occurrence of skin wrinkle and alleviating wrinkle of damaged skin. Comprehensively, the composition of the present invention can prevent and significantly alleviate skin wrinkle.

Description

[0001] The present invention relates to a composition for preventing or improving skin wrinkles comprising alpha glucopyranosyloxybenzyl alcohol as an active ingredient,

The present invention relates to a composition for preventing or improving skin wrinkles, and more particularly, to a composition for preventing or improving skin wrinkles comprising alpha glucopyranosyloxybenzyl alcohol as an active ingredient.

Skin wrinkles are known to be influenced by various factors such as skin moisture content, collagen content and immunity to the external environment. Among them, collagen production and collagenase, collagenase It is the expression and activity of Nath.

Collagen is present in the dermal layer of the skin and is known to be the main ingredient that imparts elasticity to the skin along with elastin, which accounts for about 70 to 80% of the dry weight of the skin. Collagen is reduced by internal factors such as decreased cell activity due to natural aging, and biosynthesis is reduced or accelerated by external factors such as increased stress in various harmful environments and increase of active oxygen species by sunlight have.

On the other hand, over-production of reactive oxygen species (ROS) has been reported in the UVB exposure environment, and the signaling pathways associated with UVB exposure include mitogen-activated protein kinases (MAPKs), extracellular signal- p38 kinase, and JNK (c-Jun amino-terminal kinase), which induce increased expression of NF-κB and AP-1 transcription factors. In addition, the AP-1 protein is associated with the activity of the MMP (matrix metalloproteinase) gene, and the NF-κB protein affects the expression of proinflammatory cytokines such as interleukins.

Collapse of collagen and elastin in aged skin is mainly caused by increased expression of its degrading enzyme such as MMP protein. In addition, proinflammatory cytokines interfere with the synthesis of collagen and promote collagen collapse. Type I collagen is the most abundant protein in the extracellular matrix of connective tissue. Extracellular matrix includes other types of proteins such as type III, V, and VII collagen, elastin, proteoglycan, and fibronectin.

Controlling the expression level of type I collagen protein is the most important factor in preventing skin photoaging. UVB irradiation reduces the expression of the collagen precursor procollagen in skin fibroblasts by inhibiting the TGF-β / Smad signaling pathway. In addition, the TGF-β1 signaling system is one of the important factors controlling the synthesis of extracellular matrix in human dermal fibroblasts.

Thus, the production of reactive oxygen species (ROS) regulated by AP-1 and MAPKs factors, and the expression of MMPs, ILs, TGF-ss, and type I procollagen serve as markers useful in skin photoaging studies.

Thus, there have been various attempts to discover natural substances that inhibit collagen reduction and are effective in improving skin wrinkles. In order to utilize the effect of improving the wrinkles of collagen, products containing collagen in a composition for external application for skin such as cosmetics or ointment have been marketed. However, since these products are coated on the skin surface, collagen, which is a polymer substance, The improvement effect could not be shown. To solve this problem, there has been a growing interest in collagen synthesis promoting substances. Examples of known collagen synthesis promoting substances include vitamin C, retinoic acid, transforming growth factor (TGF), animal placenta-derived proteins -231370), betulinic acid (JP8-208424), chlorella extract (JP9-40523, JP10-36283, fibroblast proliferation promoting action) and the like. However, there is a problem in that the use amount of the substance is limited or its effect is insufficient due to safety problems such as irritation and reddening when applied to the skin, so that the effect of improving wrinkles can not be expected substantially. Therefore, it is urgently required to develop a novel wrinkle-improving composition which is safer for a living body than a conventional wrinkle-improving composition and has a high wrinkle-reducing effect.

Meanwhile, Gastrodia elata Blume, Gastrodia) is a perennial plant belonging to the family Orcbidaceae. It has no chlorophyll and can not be photosynthetic of nutrients using carbon assimilation. It has no roots and symbiotes with mycorrhizal fungi (Armillarilla) and forms underground tubers (1980) In Sinssi Herbology, Summunsa, Kor, pp. 288-290). In this study, . In addition, Chunma is also called other names such as red kidney, ear poison, sprout, shincho, jungpungcho, and it is mainly used for the treatment of serious diseases such as hypertension, headache, paralysis, neurological diseases and diabetes as well as stress and fatigue It is known to have efficacy.

Among the active ingredients of Ganoderma lucidum, there is little research on the effect of ghostrodigenin (4-hydroxybenzyl alcohol) on wrinkles. We have examined the effect of ghostrodigenin on skin wrinkles, It has been found that the effect is not sufficient to be used.

Accordingly, the present inventors have synthesized compounds by forming glycosidic bonds of Gastrodigenin (4-Hydroxybenzyl alcohol), which is a skeleton of biosynthesis of gastrodine, and? Or? Forms of Gastrodigenin and its isomers, As a result of examining the effect of improving skin wrinkles, it has been found that alpha-glucopyranosyloxybenzyl alcohol in which 4-hydroxybenzyl alcohol and glucose are bound in an? -Glycoside form is used as a therapeutic agent for human dermal fibroblasts, NHDFs), it has been confirmed that the present invention has an excellent effect in preventing and improving wrinkles of the skin. Thus, the present invention has been completed.

Accordingly, it is a main object of the present invention to provide a composition comprising as an active ingredient alpha-glucopyranosyloxybenzyl alcohol having an excellent effect for preventing or improving skin wrinkles.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, there is provided a method for preventing or treating skin wrinkles comprising, as an active ingredient, a cosmetic composition for preventing or improving skin wrinkles comprising, as an active ingredient, alpha-glucopyranosyloxybenzyl alcohol Thereby providing a cosmetic composition for improvement.

The inventors of the present invention searched for a substance that is effective in the prevention of skin wrinkles and skin aging, and found that a substance which is effective in the biosynthesis of gastrodine, Gastrodigenin (4-Hydroxybenzyl Alcohols and its isomers by forming α- or β-type glycosidic bonds. After the synthesis of the compounds, their wrinkle-reducing effects were examined. As a result, 4-hydroxybenzyl alcohol and glucose were synthesized in α-glycoside form It was found that the combined alpha glucopyranosyloxybenzyl alcohol had an effect of preventing and improving excellent skin wrinkles and also showed no problem in safety when applied to skin. In particular, the above-mentioned alpha-glucopyranosyloxybenzyl alcohol is an isomer of? -Gastroloid, which is an active substance present in a natural state, and is not only safe for human body but also excellent in stability.

As used herein, the term " alpha-glucopyranosyloxy benzyl alcohol "is a material having the formula C ₁₃ H ₁₈ O ₇ and having a molecular weight of about 286.28.

The above-mentioned alpha-glucopyranosyloxybenzyl alcohol can be produced by reacting Gastrodigenin (4-Hydroxybenzyl alcohol) as a sugar receptor, cellobiose as a sugar donor, cellulase,? -Glucosidase Glucosidase) to form an? -Glycoside bond. Methods for synthesizing glycosides having an? -Glycoside bond through such an enzymatic treatment are well known to those skilled in the art (Suzuki, 1988; Kitahata, 1990; Suzuki et al., 1996; Kitahata, 2000; Maitani et al. , 2001; Thuan & Sohng, 2013).

In the cosmetic composition of the present invention, the alpha-glucopyranosyloxybenzyl alcohol may be 4-alpha-D-glucopyranosyloxy benzyl alcohol or 4-hydroxybenzyl-7-alpha Alpha -D-glucoside, and the 4-alpha-D-glucopyranosyloxybenzyl alcohol is preferably a compound of the following formula (1): 4-hydroxybenzyl- 7-alpha-D-glucoside can be represented by the following formula (2).

[Chemical Formula 1]

(2)

The alpha-glucopyranosyloxybenzyl alcohol proposed in the present invention includes all of alpha-glucopyranosyloxybenzyl alcohol salts and can be used as a wrinkle-improving material unless otherwise specified. When the above-mentioned α-glucopyranosyloxybenzyl alcohol is used in the form of a salt, an antibacterial agent, an antifungal agent, a food preservative additive, a cosmetic additive or an antifungal agent It is preferable to select a salt which is acceptable as a salt. Typically, the salt includes an acid addition salt of an inorganic acid such as a hydrochloride, a sulfate, a nitrate, a phosphate, a hydrobromide, and a hydroiodide, or an acetate, an oxalate, a malate, a bathate, a marine phosphate, a fumarate, And addition salts of organic acids such as malic acid salt, citric acid salt, tartaric acid salt, methanesulfonic acid salt and ethanesulfonic acid salt.

In the present invention, the term "skin wrinkle " means a skin formed by decay of skin, which may be caused by a cause of a gene, a decrease in collagen existing in the skin dermis, or an external environment.

In the present invention, "prevention or improvement of skin wrinkles" refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating already formed wrinkles.

The major function of dermal fibroblasts is extracellular matrix synthesis and regeneration of injured skin tissue through proliferation. The factors of extrinsic aging such as photoaging, accumulation of damage by free oxygen, and endogenous aging by cell aging due to telomere breakage Reduce the physiological activity of dermal fibroblasts in the dermal layer. Type I collagen, which accounts for more than 95% of the extracellular matrix and plays a major role in the physiological activity of fibroblasts through interactions and signal interactions with adhesion molecules and cytoskeletons of cells, Is reduced, the amount of collagen in the skin tissue is reduced, whereby the surface tension is reduced, so that the skin elasticity is lowered and the skin wrinkles are formed, and the physiological activity including cell proliferation and regeneration is decreased This causes a vicious circle.

Therefore, collagen of skin fibroblasts may be directly related to restoration or regeneration of tissue during skin regeneration, skin elasticity, wrinkle formation and skin damage.

That is, when the synthesis of collagen or procollagen of dermal fibroblast is promoted, improvement of skin elasticity, skin regeneration, improvement of skin wrinkles, wound healing, restoration and regeneration of damaged skin tissue, And prevention of skin aging can be obtained.

The composition comprising the active ingredient of the present invention increases the expression of type I procollagen protein, inhibits the expression of MMP-1, MMP-3, and MMP-9 protein, and inhibits the expression of AP-1 signaling pathway, MAPK signaling System, and the NF-kB signaling system.

Specifically, the composition comprising the alpha-glucopyranosyloxybenzyl alcohol according to the present invention reduces the cytotoxicity in normal human dermal fibroblast (NHDF) irradiated with ultraviolet rays and inhibits the degradation of collagen by the substrate protease MMP- Jun and c-Fos while inhibiting the expression of matrix metallo-proteinase (MMP) 1, 3 and 9, while increasing the production of type I procollagen, inhibiting phosphorylation of c-Jun and c- κB expression and inhibits MAPK activity, which increases skin elasticity, regenerates skin, improves skin wrinkles, heals wounds, restores and regenerates damaged skin tissue; And prevention of skin aging and the like. Specifically, it may have an effect of preventing or improving wrinkles of the skin.

The alpha glucopyranosyloxybenzyl alcohol contained in the cosmetic composition for prevention or improvement of skin wrinkles of the present invention has an effect of removing skin wrinkles by itself and is known to be effective for prevention and improvement of wrinkles of skin, It is possible to maintain the effect of preventing and improving wrinkles of the skin continuously.

Materials effective for improving the wrinkles of the skin include, but are not limited to, chamomile flower extract, rosemary leaf extract, horticulture leaf extract, earth flower extract, ginseng extract, eucalyptus leaf extract, geranium flower extract, ginseng extract eucalyptus extract, Time extract, moxa extract, nettle extract, Yarrow extract, clove extract, fennel extract, papaya leaf extract, sunflower extract, and angelica extract.

In addition, the cosmetic composition of the present invention may further comprise water-soluble vitamins, fat-soluble vitamins, polymer peptides, polymeric polysaccharides, sphingolipids and seaweed extracts.

The water-soluble vitamin may be any vitamin B, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H (Sodium thiamine hydrochloride, sodium ascorbate, etc.) and derivatives (sodium ascorbic acid-2-phosphate, magnesium ascorbic acid-2-phosphate etc.) can also be used in the present invention It is included in water-soluble vitamins. The water-soluble vitamin can be obtained by a conventional method such as a microorganism conversion method, a purification method from a culture of a microorganism, an enzymatic method, or a chemical synthesis method.

The fat-soluble vitamin may be vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol) And their derivatives (such as palmitic acid ascorbin, stearic acid ascorbic acid, dipalmitic acid ascorbin, acetic acid DL-alpha tocopherol, nicotinic acid DL-alpha tocopherol vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, Pantothenyl ethyl ether, etc.) and the like are also included in the fat-soluble vitamins used in the present invention.

The polymeric peptide may be any compound as long as it can be compounded in cosmetics, preferably collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin and the like. The polymeric peptide can be obtained by a conventional method such as purification from a culture broth of a microorganism, an enzymatic method, or a chemical synthesis method, or purified from natural products such as ducks such as pigs and cows and silk fiber of silkworms .

The polymeric polysaccharide may be any compound as long as it can be incorporated in cosmetics, and examples thereof include hydroxyethyl cellulose, xanthan gum, chondroitin sulfate or a salt thereof (sodium salt, etc.). For example, chondroitin sulfate or a salt thereof can be usually purified from mammals or fish.

The sphingogly lipids may be any of those which can be incorporated in cosmetics, and examples thereof include ceramides, phytosphingosine and sphingoglycolipids. The sphingogly lipids can be purified from ordinary mammals, fish, shellfish, yeast or plants by a conventional method or can be obtained by chemical synthesis.

The seaweed extract may be any of those which can be incorporated in cosmetics. Preferably, the seaweed extract is selected from the group consisting of algae extract, red tiger extract, green algae extract, and the like. Sodium, potassium alginate and the like are also included in the seaweed extract used in the present invention. Seaweed extract can be obtained from seaweed by a conventional method.

The cosmetic of the present invention may contain, in addition to the above-mentioned essential ingredients, other ingredients usually added to cosmetics, if necessary.

Examples of the compounding ingredients that may be added include a preservative component, a moisturizer, an emollient, an ultraviolet absorber, a pH adjuster, a flavor, a blood circulation accelerator, a cold agent, a limiting agent and purified water.

Examples of the above-mentioned sustaining component include ester-based oils, hydrocarbon-based oils, silicone-based oils, fluorine-based oils, animal oils, and plant oils.

Examples of the ester-based oil include glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearyl isostearate, Butyl stearate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isosilyl myristate, isostearic acid isostearyl, isostearyl palmitate, octyldodecyl myristate, isosertyl isostearate, diethyl sebacate, (Capryl, capric acid) glyceryl, tri-2-ethylhexanoic acid trimethylol propane, triisostearic acid trimethylol propane, tetra 2-ethylhexanoic acid pentaerythritol But are not limited to, lactose, lactate, caprylylsacetyl, lauric acid decyl, hexyl laurate, myristate decyl, myristyl myristate, myristine acid ethyl stearate, stearyl stearate, decyl oleate, But are not limited to, cetyl, lauric acid, isostearyl, isostearyl isostearyl, isostearyl isostearate, isostearyl isostearate, isostearyl palmitate, octyl stearate, isostearyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, Ethylhexanoate, stearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, di (capryl, capric acid) propylene glycol, Propylene glycol dicaprylate, propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricarboxylate, glyceryl triunsaturated acid, glyceryl triisopalmitate, glyceryl triisostearate, octyl dodecanoate Silane, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, , Octyldecyl isostearate, polyglycerin oleic acid ester, polyglycerin isostearic acid ester, triisocetyl citrate, triisolealkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, citric acid But are not limited to, triethyl citrate, acetyltriethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate , Dodecyl sebacate, stearic acid cholesteryl, isostearic acid cholesteryl, hydroxystearic acid cholesteryl, oleic acid cholesteryl, oleic acid dihydrocholesteryl, isostearic acid pitostearyl, oleic acid pitostearyl , 12-stearoylhydroxystearic acid isostearyl, 12-stearoyl stearyl hydroxystearate, 12-stearoyl stearoyl stearate, Roil-hydroxy stearic acid and the like esters such as cetearyl source.

Examples of the hydrocarbon-based oil include hydrocarbons such as squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, floating isoparaffin, polybutene, microcrystalline wax and vaseline.

Examples of the silicone-based oil include polymethyl silicone, methylphenyl silicone, methyl cyclopolysiloxane, octamethyl polysiloxane, decamethyl polysiloxane, dodecamethyl cyclosiloxane, dimethylsiloxane methyl cetyloxysiloxane copolymer, dimethylsiloxane methyl stearoxysiloxane copolymer, alkyl Modified silicone oils, and amino-modified silicone oils.

Examples of the fluorine-based oil include perfluoropolyether and the like.

Examples of the animal or plant oil include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, fresh flower oil, soybean oil, corn oil, rapeseed oil, goat oil, palm kernel oil, palm oil, castor oil, sunflower oil, Soybean oil, soybean oil, cottonseed oil, palm oil, cucumber nut oil, wheat germ oil, rice germ oil, shea butter, coltsfoot colostrum, marker daisy nut oil, meadow home oil, egg yolk oil, woji, mayo, mink oil, , Carnauba wax, liquid lanolin, hardened castor oil, and the like.

Examples of the moisturizing agent include water-soluble low-molecular moisturizing agents, oil-soluble molecular moisturizing agents, water-soluble polymers, and oil-soluble polymers.

Examples of the water-soluble low molecular weight moisturizer include serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B Polypropylene glycol (polymerization degree n = 2 or more), polyglycerin B (polymerization degree n = 2 or more), lactic acid, lactic acid salt and the like.

Examples of the lipid-soluble low-molecular moisturizing agent include cholesterol and cholesterol ester.

Examples of the water-soluble polymer include carboxyvinyl polymer, polyaspartic acid, tragacanth, xanthan gum, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, water-soluble chitin, chitosan, dextrin .

Examples of the oil-soluble polymer include polyvinyl pyrrolidone eicosene copolymer, polyvinyl pyrrolidone hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and polymer silicone.

Examples of the emollients include long chain acyl glutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, and lanolin fatty acid cholesteryl ester.

Examples of the ultraviolet absorber include para-aminobenzoic acid, ethyl paranobenzoate, amyl paranobenzoate, octyl paranobenzoate, ethylene glycol salicylate, phenyl salicylate, benzyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, Benzyl cinnamate, 2-ethoxyethyl paratomethoxy cinnamate, octyl paratomethoxy cinnamate, mono-2-ethylhexane glyceryl diflamamethoxycinnamate, isopropyl paratumoxycinnamate, diisopropyl-diisopropyl cinnamate ester mixture , Urocannic acid, ethyl urocanoate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and salts thereof, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenone disulfonate, dihydroxy Benzophenone, tetrahydroxybenzophenone, 4-tert-butyl-4'-methoxydibenzoylmethane, 2,4,6-trianylino-p- (carbo-2'-ethylhexyl- -1,3,5-triazine, 2- (2-H And the like can be mentioned hydroxy-5-methylphenyl) benzotriazole.

Examples of the pH adjusting agent include citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogenphosphate and the like.

In addition, any of the above components may be blended within the range not to impair the objects and effects of the present invention, but it is preferably 0.01 to 20 parts by weight, Preferably 0.01 to 5 parts by weight.

The cosmetic preparation prepared by containing the composition of the present invention may take the form of a solution, an emulsion, a viscous mixture or the like.

In addition, the components contained in the cosmetic composition of the present invention may contain, as an active ingredient, the components commonly used in cosmetic compositions in addition to the above components, for example, conventional additives such as stabilizers, pigments and natural flavors, And may further comprise a carrier.

The composition of the present invention can be variously used in cosmetics or cleansers having an effect of preventing and improving wrinkles of the skin.

Examples of products to which the composition of the present invention can be added include a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, Cosmetics such as foundation, essence, nutrition essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser.

When the formulation of the present invention is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.

In the case of the solution or emulsion of the present invention, a solvent, a solvent or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

According to another aspect of the present invention, there is provided a pharmaceutical composition for preventing or improving skin wrinkles comprising alpha glucopyranosyloxybenzyl alcohol as an active ingredient.

In the pharmaceutical composition for preventing or improving skin wrinkles according to the present invention, the alpha-glucopyranosyloxybenzyl alcohol may be 4-alpha-D-glucopyranosyloxy benzyl alcohol or 4 Alpha-D-glucoside, and the 4-alpha-D-glucopyranosyloxybenzyl alcohol may be 4-hydroxybenzyl-7-alpha-D-glucoside 4-hydroxybenzyl-7-alpha-D-glucoside can be represented by the following formula (2).

[Chemical Formula 1]

(2)

In the pharmaceutical composition for preventing or improving skin wrinkles of the present invention, the expression of type I procollagen protein is increased, the expression of MMP-1, MMP-3, and MMP-9 protein is inhibited, Delivery system, MAPK signaling system, and NF-kB signaling system.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The pharmaceutical dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts and may also be used alone or in combination with other pharmaceutically active compounds.

Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

When the composition of the present invention is formulated, it is prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, and surfactants which are generally used.

The composition of the present invention can be applied to the skin and is directly applied to the skin in the form of external preparation for skin such as cream, gel, patch, spray, ointment, warning agent, lotion, liniment, pasta or cataplasma But is not limited thereto.

The preferred dosage of the mixed composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but may be suitably selected by those skilled in the art, Lt; RTI ID = 0.0 > g / ml. ≪ / RTI > External administration may be administered once a day or divided into several doses.

The cosmetic composition and the pharmaceutical composition of the present invention can be used directly as a composition for preventing or improving skin wrinkles since it has an effect of preventing or improving wrinkles of the skin itself, It is expected that it will be possible to improve the prevention or improvement effect of the existing wrinkles of the skin.

As described above, the composition of the present invention increases the expression of type I procollagen protein in human dermal fibroblasts, inhibits the expression of MMP-1, MMP-3, and MMP-9 proteins, System, the MAPK signaling system, and the NF-kB signaling system, thereby preventing the occurrence of skin wrinkles and improving the wrinkles of damaged skin. In general, the composition of the present invention can prevent and greatly improve skin wrinkles.

In addition, the composition of the present invention is an isomer of? -Gastroloid, which is an active substance present in a natural state, and is very safe for the human body as well as excellent in stability.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic diagram showing a method for synthesizing the alpha glucopyranosyloxybenzyl alcohol of the present invention. Fig.
2 is a graph showing that the treatment of alpha glucopyranosyloxybenzyl alcohol in human fibroblasts does not significantly affect cell viability (4HBA: 4-hydroxybenzyl alcohol, 4HBA4? G: 4-α-D-glucopyranosyloxy benzyl alcohol, 4HBA7 [alpha] g: 4-hydroxybenzyl-7- [alpha] -D-glucoside).
3 is an ELISA assay showing the expression pattern of MMP-1 protein upon treatment with alpha glucopyranosyloxybenzyl alcohol in human fibroblasts.
4 is an ELISA assay showing the expression pattern of MMP-3 protein upon treatment with alpha glucopyranosyloxybenzyl alcohol in human fibroblasts.
FIG. 5 is a graph showing that treatment of 4-alpha-D-glucopyranosyloxy benzyl alcohol (-gastrodin) in human fibroblasts does not significantly affect cell viability.
6 is an ELISA assay showing the expression pattern of MMP-1 protein upon treatment with 4-alpha-D-glucopyranosyloxy benzyl alcohol (alpha-gastrodin) in human fibroblasts.
7 is an ELISA assay showing the expression pattern of MMP-3 protein upon treatment with 4-alpha-D-glucopyranosyloxy benzyl alcohol (alpha-gastrodin) in human fibroblasts.
8 is an ELISA assay showing the expression pattern of MMP-9 protein upon treatment with 4-α-D-glucopyranosyloxy benzyl alcohol (α-gastrodin) in human fibroblasts.
FIG. 9 is a graph showing the expression patterns of type 1 procollagen and MMP gene following treatment with 4-α-D-glucopyranosyloxy benzyl alcohol (α-gastrodin) in human fibroblasts.
10 is an analysis of the degree of phosphorylation of c-Jun and c-Fos proteins by 4-alpha-D-glucopyranosyloxy benzyl alcohol (alpha-gastrodin) treatment in human fibroblasts.
11 is a graph showing the degree of phosphorylation of p38 protein and JNK protein by 4-alpha-D-glucopyranosyloxy benzyl alcohol (alpha-gastrodin) treatment in human fibroblasts.
12 is an analysis of the expression pattern of NF-κB protein by 4-α-D-glucopyranosyloxy benzyl alcohol (α-gastrodin) treatment in human fibroblasts.

Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for illustrating the present invention, and thus the scope of the present invention is not construed as being limited by these embodiments.

Example 1 Preparation of Alpha Glucopyranosyloxybenzyl Alcohol and Component Analysis

1-1. β-glycoside synthesis

(BA), 2-hydroxybenzyl alcohol (IHBA), 3-hydroxybenzyl alcohol (3-HBA) and 4-hydroxybenzyl alcohol (4HBA) as a sugar acceptor were mixed with 10 g of cellobiose as a saccharide donor, Was dissolved in 0.1 M acetic acid buffer solution (pH 4.8) in an amount of 2.0 g, and the solution was then added in a volume of 100 mL. 100 mg (6,000 U) of Asp niger cellulase (MP Biomedicals) having β-glucosidase activity Followed by reaction at 37 캜 for 48 hours with stirring. After completion of the reaction, each reaction solution was heated in a boiling water bath for 10 minutes to inactivate the enzyme, and then used as a sample for separating reaction products by column chromatography.

1-2. α-glycoside synthesis

(BA), 2-hydroxybenzyl alcohol (IHBA), 3-hydroxybenzyl alcohol (3-HBA) and 4-hydroxybenzyl alcohol (4HBA) as a sugar receptor as a sugar donor, Were prepared, and 2,250 U of CGTase stored in 1 ml of 0.1 M CaCl ₂ solution and the prepared sugar donor and the sugar receptor were added to 0.1 ml of acetic acid buffer solution (pH 6.0), and the volume was adjusted to 100 ml. The reaction solution was allowed to react for 48 hours while stirring in a dark place at 50 ° C, and then the enzyme was inactivated by heating in a boiling water bath for 10 minutes. The pH of the reaction solution was adjusted to 5.0 using 1.0 M acetic acid aqueous solution to hydrolyze malto-oligosylglucosides produced by the reaction with CGTase into monoglucoside, 80 units (U) of glucoamylase was added and hydrolysis was carried out for 8 hours while stirring at 50 ° C. The reaction solution was heated in a boiling water bath for 10 minutes to inactivate glucoamylase and then used as a sample for the separation of reaction products by column chromatography.

1-3. Separation of reaction products

As a process for separating the glycoside produced by the sugar transfer reaction produced in the above Examples 1-1 and 1-2, the free form of the aromatic alcohol remaining in each reaction solution was dissolved in chloroform ). Subsequently, the reaction solution was adsorbed on a Diaion HP-20 filled column (3 cm x 30 cm), washed with 200 mL of distilled water to remove saccharides, and 200 mL of methanol was used to elute the generated glycoside. The methanol eluate was concentrated under reduced pressure and then further separated by silica gel column chromatography. The silica gel (70 to 230 mesh) was filled in a glass column (3 cm × 25 cm) about 50 times as much as the sample, and then a mixture of chloroform-methanol-water (80:20:2, 70:30: 3, The purity of the separated reaction products was confirmed by HPLC, and the structure was identified using a Positive-ESI-HPLC-MS instrument. Respectively.

[Table 1]

4-hydroxybenzyl alcohol (4-HBA) synthesized from the synthesized? -Glycosyl gypsum products, 4-hydroxybenzyl-7-α-D-glucoside (A- -D-glucopyranosyloxy) benzyl alcohol (A-5bG) are summarized in Tables 2 and 3 below.

[Table 2]

[Table 3]

Example 2: Effect of improving the wrinkle of alpha-glucopyranosyloxybenzyl alcohol

2-1. Cytotoxicity Assessment

The effect of alpha glucopyranosyloxybenzyl alcohol on the growth of human dermal fibroblasts (NHDF) was confirmed by the following method.

First, dermal fibroblasts were inoculated into DMEM (Dulbeccos modified Eagles medium), a medium containing 10% FBS (fetal bovine serum, Cambrex), at a concentration of 1.2 × 10 ⁵ in a 40 mm cell culture dish, , And cultured at 37 占 폚 and 5% CO ₂ wetting conditions. Thereafter, the medium was removed, 300 용량 volume of PBS was added, and UVB (UVB peak range: 312 nm, UV dose: 144 mJ / cm 2) was irradiated. Alpha glucopyranosyloxybenzyl alcohol samples were prepared by adding 4-hydroxybenzyl-7-α-D-glucoside (A-5aG) and 4- (α-D-glucopyranosyloxy) benzyl alcohol (A-5bG) (1, 10, 100 ㎍ / mL) and cultured for 72 hours. As a control, 4 - hydroxy - benzyl alcohol was used as a control. After 72 hours, 1 mg / mL of MTT was treated and 2 hours later, the formazan produced by MTT treatment was dissolved in DMSO and the absorbance was measured at 570 nm.

As a result, it was confirmed that when the human skin fibroblasts were treated with alpha glucopyranosyloxybenzyl alcohol, the alpha glucopyranosyloxybenzyl alcohol did not significantly affect the cell viability (see Fig. 2) It was confirmed that the glucopyranosyloxybenzyl alcohol did not show toxicity to human skin fibroblasts.

2-2. Inhibition of MMP-1 and MMP-3 protein expression

40mm cell into the culture medium of DMEM 2㎖ a Petri dish, and then inoculated with human fibroblasts in a concentration of about 1.2x10 ^5, and incubated for 24 hours at 37 ℃, 5% CO ₂ environment. Thereafter, UVB was irradiated under conditions of 144 mJ / cm ² , and the cells were cultured for 3 days by replacing with medium containing alpha glucopyranosyloxybenzyl alcohol (1, 10, and 100 μg / ml, respectively). 4-hydroxybenzyl-7-α-D-glucoside (4HBA7αG) and 4- (α-D-glucopyranosyloxy) benzyl alcohol (4HBA4αG) were used as the α-glucopyranosyloxybenzyl samples. As a control, 4-hydroxybenzyl alcohol Respectively. The cultures were then harvested and centrifuged at 7500 rpm for 5 min at 4 ° C to obtain MMP-1 and MMP-3 (Human Total MMP-1 kit; R & D Systems, Inc., Minneapolis, MN, USA) (see FIGS. 3 and 4).

As a result, it was confirmed that the production of collagenolytic enzymes MMP-1 (FIG. 3) and MMP-3 (FIG. 4), which were increased in expression by ultraviolet irradiation, was greatly suppressed.

As a result, the composition containing the alpha-glucopyranosyloxybenzyl alcohol of the present invention inhibits the expression of collagenase, MMP-1 and MMP-3, effectively prevents wrinkle formation, It was confirmed that there is an effect of improving the generated wrinkles.

Example 3: Improvement of skin wrinkles of? -Gastrodine In-depth verification

3-1. Suppression of MMP protein expression

D-glucopyranosyloxy) benzyl alcohol (4HBA4? G), which is the most effective in Example 2, was tested according to the method of Example 2 to determine the cytotoxicity and MMP-1 , And the effects of MMP-3 and MMP-9 proteins on expression are shown in FIGS. 5 to 8. FIG. As a result, results similar to those of Example 2 were obtained. In particular, in the case of expression of MMP-9 protein, it was confirmed that the addition of? -Gastronin suppressed the concentration-dependent manner.

3-2. Promoting mRNA expression and inhibiting mRNA expression of MMP-1 in Type-1 Procollagen

100mm cell into the culture medium of DMEM 10㎖ a Petri dish, then the cell the human fibroblasts at a concentration of about 6x10 ⁵ inoculation, was incubated at 37 ℃, 5% CO ₂ environment for 24 h. Thereafter, UVB was irradiated under the condition of 144 mJ / cm < ² > and then cultured for 24 hours by replacing with a medium containing? -Gastronin (1, 10, 50 占 퐂 / ml).

The cells were then harvested with 1 ml of TRIZOL reagent to isolate RNA. The amount of mRNA expression of type 1 procollagen (Type-1 Procollagen) and MMP-1 was confirmed by RT-PCR. The primers used were as follows.

- MMP-1: forward 5'-ATT CTA CTG ATA TCG GGG CTT TGA-3 ', reverse 5'-ATG TCC TTG GGG TAT CCG TGT AG-3'

- Type 1 Procollagen: Forward 5'-CTC GAG GTG GAC ACC ACC CT-3 ', Reverse 5'-CAG CTG GAT GGC CAC ATC GG -3'

- GAPDH: forward 5'-ACC ACA GTC CAT GCC ATC AC-3 ', reverse 5'-CCA CCA CCC TGT TGC TGT AG-3'.

RT-PCR was performed using the primers described above, and the results are summarized in FIG. From the results shown in FIG. 9, it was found that? -Gastronin effectively inhibited mRNA expression of MMP-1 and significantly increased mRNA expression of type 1 procollagen. From these results, It has been confirmed that? -gastrodine effectively prevents wrinkle formation and improves the formed wrinkles.

3-3. Inhibition of phosphorylation of c-Jun and c-Fos

Into the culture medium of DMEM 10㎖ in cell culture dishes of 100 mm size, and then inoculated with human fibroblasts in a concentration of approximately 6x10 ^5, in 37 ℃, 5% CO ₂ environment, allowed to incubate for 24 hours. Thereafter, the cells were irradiated under the condition of ultraviolet ray B at 144 mJ / cm ² and then cultured for 4 hours by replacing with a medium containing? -Gastrodine (1, 10, and 50 μg / ml, respectively). The amount of phosphorylated expression of c-Jun and c-Fos was confirmed by western blot analysis, and the results are shown in FIG.

As a result, the phosphorylation of c-Jun and c-Fos stimulated by ultraviolet light increased to 224% and 276%, respectively, compared with the untreated group, but 70% and 34% And it was confirmed that it was greatly suppressed.

These results indicate that the? -Gastrodyne compound of the present invention inhibits the activation of the AP-1 signaling pathway, thereby inhibiting the production of MMP protein or interleukin that degrades proteins constituting the extracellular matrix, It was confirmed that the effect of preventing wrinkle formation effectively and improving the formed wrinkles was confirmed.

3-4. MAPK phosphorylation inhibition

In Example 3-3, it was found that? -Gastronin inhibits AP-1 promoter activity. Western blot analysis was performed to determine whether the inhibitory action of? -Gastrin was caused by the influence of protein kinase which induces AP-1 promoter activity. First, human normal fibroblast cells were irradiated with ultraviolet B under conditions of 144 mJ / cm ² , and then cultured for 1 hour by replacing with medium containing? -Gastrodine (1, 10, 50 占 퐂 / Respectively. After 1 hour, the cells were harvested and western blotted to phospho-JNK and phospho-p38 mapk (Cell signaling technology). As shown in Fig. 11, a-gastrodin inhibited the phosphorylation of JNK, but did not show any inhibitory effect on the phosphorylation of p38mapk. Based on these results, it was found that? -Gastronin inhibits the activity of JNK in inhibiting the AP-1 promoter, thereby exhibiting its inhibitory action. Furthermore, it was found that the inhibitory activity of collagenase activity was also suppressed through the inhibition of JNK activity.

3-5. Inhibition of NF-κB production

Into the culture medium of DMEM 10㎖ in cell culture dishes of 100 mm size, and then inoculated with human fibroblasts in a concentration of approximately 6x10 ^5, in 37 ℃, 5% CO ₂ environment, allowed to incubate for 24 hours. Ultraviolet B was then irradiated under the condition of 144 mJ / cm ² , and then the medium was replaced with a medium containing? -Gastrodine (10, 50 μg / ml, respectively) and cultured for 1 hour. The expression level of NF-κB was confirmed by western blot analysis and the results are shown in FIG.

As a result, the expression of NF-κB stimulated by ultraviolet light was increased to 194%, respectively, compared with the untreated group, but it was decreased to 51% as compared with the ultraviolet-treated group by α-gastrodine treatment.

These results suggest that the α-gastroin of the present invention inhibits the activation of the NF-κB signaling pathway and thereby inhibits the expression of proinflammatory cytokines such as interleukin. It was effectively prevented and the effect of improving the formed wrinkles was confirmed.

Claims (11)

A cosmetic composition for preventing or improving wrinkles of skin comprising, as an active ingredient, alpha-glucopyranosyloxy benzyl alcohol. The method according to claim 1,
The alpha-glucopyranosyloxybenzyl alcohol may be 4-alpha-D-glucopyranosyloxy benzyl alcohol or 4-hydroxybenzyl-7-alpha-D-glucoside (4- hydroxybenzyl-7-alpha-D-glucoside). 3. The method of claim 2,
Wherein the 4-alpha-D-glucopyranosyloxybenzyl alcohol has the formula of the formula 1 and the 4-hydroxybenzyl-7-alpha-D-glucoside has the formula .
[Chemical Formula 1]

(2)

The method according to claim 1,
Wherein said alpha glucopyranosyloxybenzyl alcohol increases the expression of type I procollagen protein and inhibits the expression of MMP-1, MMP-3, and MMP-9 proteins. The method according to claim 1,
The composition may be selected from the group consisting of chamomile flower extract, rosemary leaf extract, horticulture leaf extract, earth flower extract, ginseng extract, geranium flower extract, ginseng extract, moxa extract, time extract, nettle extract, Yarrow extract, Wherein the cosmetic composition further comprises at least one plant extract selected from extracts, sunflower extract, and angelica extract. The method according to claim 1,
The composition may be in the form of a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisturizing cream, a hand cream, a foundation, , A cleansing lotion, a cleansing cream, a body lotion and a body cleanser. A pharmaceutical composition for preventing or improving wrinkles of skin comprising, as an active ingredient, alpha-glucopyranosyloxy benzyl alcohol. 8. The method of claim 7,
The alpha-glucopyranosyloxybenzyl alcohol may be 4-alpha-D-glucopyranosyloxy benzyl alcohol or 4-hydroxybenzyl-7-alpha-D-glucoside (4- hydroxybenzyl-7-a-D-glucoside). 9. The method of claim 8,
Wherein the 4-alpha-D-glucopyranosyloxybenzyl alcohol has the formula of the formula 1 and the 4-hydroxybenzyl-7-alpha-D-glucoside has the formula Composition.
[Chemical Formula 1]

(2)

8. The method of claim 7,
Wherein said alpha glucopyranosyloxybenzyl alcohol increases the expression of type I procollagen protein and inhibits the expression of MMP-1, MMP-3, and MMP-9 proteins. 8. The method of claim 7,
Wherein the pharmaceutical composition is one selected from the group consisting of cream, gel, patch, spray, ointment, warning agent, lotion, liniment, pasta, and cataplasma.

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