KR20190033334A - External Composition for Skin Containing the Mixture of the Root Extract of Taraxacum officinale, Caffeine and Tocopherol - Google Patents

Abstract

The present invention relates to a skin external preparation composition containing a mixture of a dandelion root extract, caffeine, and tocopherol. More specifically, the present invention relates to the skin external preparation composition containing the dandelion root extract, caffeine, and tocopherol as active components for skin barrier enhancement, skin moisturizing enhancement, skin turnover promotion, skin anti-oxidation or skin anti-aging. The skin external preparation composition containing the mixture of the dandelion root extract, caffeine, and tocopherol according to the present invention, can be used for manufacturing medicines or cosmetics having a function of skin barrier enhancement, skin moisturizing enhancement, skin turnover promotion, skin anti-oxidation or skin anti-aging.

Description

[0001] The present invention relates to a composition for external application for skin, which comprises a mixture of dandelion root extract, caffeine and tocopherol,

The present invention relates to a composition for external application for skin comprising a mixture of dandelion root extract, caffeine and tocopherol, and more particularly to a composition for external application for skin comprising dandelion root extract, caffeine and tocopherol as active ingredients, Accelerating, skin antioxidant or skin anti-aging.

The most important function of the epidermis in the outermost skin is to protect against external stimuli (chemical, air pollutants, dry environment, physical and chemical stimulants such as ultraviolet rays) This protective function can maintain its function only when the stratum corneum composed of keratinocytes is normally formed. The outermost stratum corneum (horney layer) of the epidermis is formed from keratinocytes and consists of keratinocytes with complete differentiation and a surrounding lipid layer (Elias, J. Invest. Dermatol ., 80:44 -49, 1983). The keratinocyte is a characteristic cell in which basal cells continuously proliferating in the lowest epidermis undergo a stepwise change in morphology and function and are elevated to the surface of the skin. After a certain period of time, And the new keratinocyte replaces its function. This repetitive sequence of changes is called "epidermal cell differentiation" or "keratinization". During keratinization, keratinocytes form the stratum corneum while producing natural moisturizing factors (NMF) and intercellular lipids (ceramides, cholesterol, fatty acids), which make the stratum corneum firm and flexible, As shown in Fig.

However, these stratum corneum can easily lose its function due to excessive skin cleansing, lifestyle factors such as bathing, environmental factors such as dry air and pollutants, and endogenous diseases such as atopic skin and senile skin, The number of people who are complaining of dry skin symptoms and various disorders due to increased factors is increasing recently. Therefore, in order to maintain proper skin moisture, studies have been conducted to supply moisture from the outside or to prevent water loss from the body, and a variety of moisturizers having moisture retention ability have been developed, It is widely used in the area.

In the living environment, the risk factors for the human being are increasingly increasing, the aging population is rapidly increasing, the turnover rate of the stratum corneum is delayed, the lipogenesis ability of keratinocytes is decreased, It is difficult to maintain the function of the normal stratum corneum due to the decrease of the amount of the moisturizing factor and lipid of the stratum corneum due to the lack of cleavage, division, maturation and differentiation of the stratum corneum. There is a tendency.

Due to the abnormal division and differentiation of the epidermal cells, the skin causes various skin diseases such as dry skin, atopy and psoriasis. Such a disease can slightly alleviate the symptoms only by a conventional moisturizing agent having only moisture holding function , But it is difficult to expect fundamental healing.

In general, sebaceous glands in the skin, including the scalp and face, play a role in preventing moisturization and microbial invasion of the skin. However, excessive secretion of sebum promotes hair loss, worsens acne, promotes enlargement of pores caused by acne, And many other diseases are caused.

The human skin undergoes changes due to various internal and external factors as it gets older. In other words, internally, secretion of various hormones that regulate metabolism is reduced, the function of immune cells and the activity of cells are lowered, and the biosynthesis of immune proteins and biocompatible proteins necessary for the living body is reduced, and ozone layer destruction As the content of ultraviolet rays reaching the surface of the sunlight increases and environmental pollution is further intensified, free radicals and active noxious oxygen are increased, so that the thickness of the skin decreases, the wrinkles increase, the elasticity decreases Skin color is grayish, skin troubles occur frequently, and spots, freckles and black blots also increase.

As the aging progresses, the content and arrangement of collagen, elastin, hyaluronic acid and glycoprotein, which constitute the skin, are changed or decreased, and oxidative stress due to free radicals and active noxious oxygen is experienced. In addition, most of the cells that constitute the skin undergo aging or ultraviolet rays, Cox-2 (cyclooxygenase-2), an enzyme that produces proinflammatory cytokines known to cause inflammation ), Biosynthesis of matrix metalloproteinase (MMP), which is an enzyme that degrades skin tissue, is increased by these inflammatory factors, nitric oxide (NO) production by iNOS (inducible nitric oxide synthase) Is known to increase.

In other words, the decrease of cell activity due to natural endogenous aging and the decrease of biosynthesis of substrate materials due to microinflammation, the increase of stress caused by various harmful environments, and the increase of active oxygen species by sunlight The skin is degraded and thinned and the symptoms of skin aging are revealed. Therefore, it is a reality that many researches have been conducted on active ingredients that can prevent and improve such aging phenomena.

Studies on antioxidants have shown that McCord and Fridovich discovered superoxide dismutase (SOD), an enzyme that clears superoxide radicals, in 1969, I was interested in it.

Free radicals such as superoxide are generated in the body by external stress, ultraviolet rays, smoking, drugs, active oxygen, etc., and are non-selective and irreversible destructive action against cellular components such as lipids, proteins, sugars and nucleic acids It is known that it causes various diseases such as aging, brain diseases such as stroke, Parkinson's disease, heart disease, ischemia, arteriosclerosis, skin diseases, digestive diseases, inflammation, rheumatism and autoimmune diseases including cancer. These free radicals cause various dysfunctions due to oxidative destruction of cells, which can cause aging and disease.

Recently, it has been found that active oxygen and superoxide directly act on various diseases and aging. Therefore, antioxidant research has been shifting from research on the development of antioxidants as food additives to research on antioxidants as antioxidants and disease treatments .

Dandelion (Taraxacum officinale , and Dandelion) is a perennial herb that grows on the roadsides and blooms, and blooms in April and May, and contains a large amount of useful pharmacological ingredients. In one room, it is said that the dandelion outpost which is dried before flowering is called as pongolyong, and it is said that it has action to lower heat, to urinate well, to remove inflammation, to strengthen stomach, to clear poison, Tissue, fever, diuretic, dryness, genomes, and detoxification.

The dandelion contains components such as taraxasterol, choline, inulin and pectin, and specifically, the dandelion root contains taraxol, taraxenol, taraxel sterol, betamirin, stigmasterol, choline (50 to 70 mg / 100 g) and vitamin D (5 to 9 mg / 100 g) are added to the dandelion leaves, and the dandelion leaves are selected from the group consisting of rutin, viola xanthine, plastoquinone, vitamin C , And dandelion flowers contain alnidiols, rutin and flavanthin (Oriental Medicine Dictionary, Kyung Hee University Press, p514, 1999). Dandelion is a special ingredient that contains inulin, sterol, choline, palmitin, and serine. Especially, linoleic acid and choline in dandelion are known to be effective for diseases such as hypertension, heart disease and liver disease (Kim et al. , Free radical , YeoMoonGak, Seoul, 1997).

Studies on the constituents of these plants in the order of Dandelion have found that ρ-hydroxyphenylacetic acid, 3,4-dihydroxycinnamic acid, melissic acid, It has been reported that many active ingredients such as taraxasteryl acetate, corn syrup, tallacerol, and ψ-tardacosterol have been isolated (Hwang Woon-kyun, et al., The Phenolic Activity of Some Dandelion (Ⅰ) 25 (3): 209-213, 1994; and Hans-Willi R and Jai-tung H, Phytochemistry , 24: 1557-1562, 1985). In the West, dandelion has been used as a medicinal agent in the promotion of bile secretion, antirheumatics and diuretic (Yang KS and Jeon CM, Korean J. Pharmacogn. , 27: 267-273, 1996). Dried dandelion leaves and roots are used as coffee substitutes (Jeong JY et al. , Arch Pharm Res. , 14: 68-72, 1991). In particular, the polyphenol compounds such as flavonoids, luteolin, cinnamic acid, coumarin, (Williams CA et al. , Phytochemistry , 42: 121-127, 1996).

Caffeine is a type of alkaloid in fruits, leaves and seeds of some plants, such as coffee or tea. It has a xanthine structure with three methyl groups in structure (C ₈ H ₁₀ O ₂ N ₄ ) It is a white crystal. Caffeine has the pharmacological action of central nervous system stimulants, cardiotonic agents, diuretics, and has the effect of decomposing fat, especially cellulite. That is, since caffeine inhibits the activity of nucleotide phosphodystease to increase the amount of cAMP, thereby promoting the activity of triacylglycerol lipase and promoting lipolysis, it is widely used in slimming cosmetics for body lines It is the ingredient used. In addition, caffeine is known to play a role in removing skin cells damaged by UV rays in the skin.

Tocopherol, also called vitamin E, is known to be synthesized in green plants and photosynthetic bacteria. It is abundant in many vegetable oils such as soybean, wheat, corn, rice, cotton, Alfalfa and nuts, and also contains fruits and vegetables such as raspberries, peas, peas, . In general, tocopherol exists as four homologues of alpha (-), beta (-), gamma (-) and delta (-). The homologues are distinguished by the number and position of the methyl group (CH ₃ ) attached to the aromatic ring constituting the tocopherol molecule (Hess, In Antioxidants in higher plants (Alscher RG, Hess JL eds.), CRC Press, Boca Raton, FL. Pp. 111-134, 1993). Among them, α-tocopherol is the most effective vitamin E ingredient in nutrition, and has the highest bioactivity. The α-tocopherol has the highest vitamin E activity and the vitamin E activity is about 9 times higher than that of γ-tocopherol (Machlin, In Handbook of Vitamins (Machlin LJ ed.), Marcel Dekker, New York, NY pp. 99-150, 1991).

The substance that acts on vitamin E is tocol, 2-methyl-2- [tri-methyl-tridecyl] -6-hydroxychromane ) As a basic skeleton. The side chain of tocopherol is derived from phytol, and the trienol having a double bond at the 3 ', 7', and 11 'positions of the side chain has a structure similar to the tocol. Tocol and trienol are various isomers by the position and number of the methyl group in the chroman ring.

Tocopherol has antioxidant activity and has an action to prevent the oxidation of vitamin A in vivo. It is also used for toothpaste to prevent periodontitis. The antioxidant activity of tocopherol isomer is superior to delta tocopherol at the ratio of alpha: beta: gamma: delta = 1: 1.3: 1.8: 2.7 at room temperature. Tocopherol itself is unstable and many derivatives of it are used. Especially, various kinds of derivatives such as vitamin acetate and vitamin palmitate are present.

Under these technical backgrounds, the present inventors have made intensive efforts to develop a composition for external application for improving skin condition. As a result, they have found that dandelion root extract, caffeine and tocopherol are more preferable than a mixture of one or two selected from the group consisting of dandelion root extract, caffeine and tocopherol Has an effect of enhancing the barrier function of the skin and remarkably increasing the antioxidant efficacy. Thus, the present invention has been completed.

The object of the present invention is to provide a composition for external application for skin, which comprises a mixture of dandelion root extract, caffeine and tocopherol as an active ingredient according to the present invention, preferably a composition for strengthening skin barrier, enhancing skin moisturizing power, promoting skin turnover, And to provide an external-use composition for improving the aging efficacy.

In order to achieve the above object, the present invention provides an external preparation for skin comprising a mixture of Dandelion root extract, caffeine and tocopherol as an active ingredient, preferably a skin barrier strengthening agent containing the above-mentioned mixture as an active ingredient, Over-accelerating, skin antioxidant or skin anti-aging.

The composition for external application for skin comprising a mixture of dandelion root extract, caffeine and tocopherol according to the present invention can be used for the manufacture of medicaments and cosmetics having skin barrier enhancement, skin moisturizing, skin turnover promotion, skin antioxidant or anti-aging function .

FIG. 1 shows the antioxidative activity of Dandelion Root Extract Compared with the Antioxidant Activity of Vitamin C (Vit C).
Figure 2 shows the antioxidant power of a mixture of dandelion root extract, caffeine and tocopherol (on a ppm basis, 10: 1000: 100).
FIG. 3 shows CLDN4 mRNA expression levels of keratinocytes by treatment with a mixture of dandelion root extract, caffeine and tocopherol (ppm: 10: 1000: 100).

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

Hereinafter, the present invention will be described in more detail.

The term " about " as used herein to describe volume, time (period), concentration, content, area, temperature, etc. means that there is a maximum tolerance of 10% in that numerical or numerical range.

Throughout this specification, "%" used to denote the concentration of a particular substance is intended to include solids / solids (wt / wt), solid / liquid (wt / The liquid / liquid is (vol / vol)%.

In one embodiment of the present invention, the antioxidative effect of a mixture of dandelion root extract, caffeine and tocopherol is evaluated by measuring DPPH (1,1-diphenyl-2-picrylhydrazide; 1,1-diphenyl -2-picryl hydrazyl) assays. As a result, a mixture of a sample (dandelion root extract, caffeine or tocopherol) or a mixture of two samples (mixture of dandelion root extract and caffeine, mixture of dandelion root extract and tocopherol, or mixture of caffeine and tocopherol) The mixture of three samples (dandelion root extract, mixture of caffeine and tocopherol) showed the lowest IC ₅₀ value and the highest antioxidant power. Concretely, when the dandelion root extract, caffeine and tocopherol were mixed in a concentration of 8-12: 800-1200: 80-120 on the basis of ppm concentration, the IC ₅₀ value was low and high antioxidant power , And it was confirmed that when the dandelion root extract, caffeine and tocopherol were mixed at a concentration of 9 to 11: 900 to 1100: 90 to 110 in terms of ppm concentration, they had lower IC ₅₀ value and higher antioxidant power, In particular, when the concentration of Dandelion root extract: caffeine: tocopherol was 10: 1000: 100 on the ppm concentration basis, the lowest IC ₅₀ value was found to have the highest antioxidant ability (see Experimental Example 1).

In another embodiment of the present invention, the mixture (100% treated concentration) and its diluted solution (1.5625 to 50% treated concentration) prepared at a mixing ratio of dandelion root extract: caffeine: tocopherol = 10: 1000: The antioxidant capacity was compared. As a result, as shown in FIG. 2, (i) the antioxidant power was increased (the DPPH activity was reduced by 20 to 80%) in proportion to the treatment concentration range of 1.5625 to 12.5% (Iii) the treatment concentration required to reduce the DPPH activity by 50% was 5.5% (IC (i)), and (ii) ₅₀ = 5.5%) (see Experimental Example 1).

In another embodiment of the present invention, the skin barrier enhancement effect of a mixture of dandelion root extract, caffeine and tocopherol is measured by measuring the mRNA expression level of CLDN4 (Claudin 4) involved in the formation of close junction (Tight Junction, TJ) Respectively. As a result, as shown in Fig. 3, (i) the amount of mRNA expression of CLDN4 was increased in proportion to the treatment concentration in the treatment concentration range of 12.5 to 100%, and (ii) (See Experimental Example 2).

Accordingly, in one aspect, the present invention provides a composition for external application for skin comprising a mixture of dandelion root extract, caffeine and tocopherol as an active ingredient, preferably a skin barrier strengthening agent containing the above-mentioned mixture as an active ingredient, , Skin turnover promotion or skin antioxidation, and a cosmetic composition.

The dandelion root extract can be extracted by a known natural substance extraction method and is preferably extracted with at least one solvent selected from the group consisting of water, organic solvents having 1 to 6 carbon atoms, and subcritical or supercritical fluids, The organic solvent having 1 to 6 carbon atoms may be an alcohol having 1 to 6 carbon atoms, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride chloride, hexane, cyclohexane, and petroleum ether.

The solvent used for preparing the dandelion root extract may more preferably be water, an alcohol having 1 to 6 carbon atoms or a mixture thereof, and the alcohol having 1 to 6 carbon atoms may be ethanol. The amount of the solvent may vary depending on the amount of the dandelion roots to be extracted, and may be preferably 1 to 20 times the volume of the dandelion root, and more preferably 3 to 10 times the volume of the dandelion root.

The extraction temperature of the dandelion root extract is not particularly limited and may be, for example, 0 ° C to 120 ° C, preferably 50 ° C to 100 ° C. The extraction time of the extract of the present invention is not particularly limited, and may be, for example, 1 hour to 10 days, preferably 2 hours to 6 hours.

The dandelion root extract can be extracted by a known natural material extraction method. For example, it can be extracted by cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, or heat extraction, preferably by hot water extraction or reflux cooling extraction. The extraction can be performed once to 10 times, preferably twice To 7 times.

The dandelion root extract can be used as a liquid phase by filtration, and can be solidified through spray drying or lyophilization drying process. More preferably, the dextrin can be mixed and dried before spray drying or freeze-drying.

In the present invention, the mixture of dandelion root extract, caffeine and tocopherol is preferably used in an amount of 8-12: 800-1200: 80-120, more preferably 9-11: 900, in terms of ppm concentration of dandelion root extract, caffeine and tocopherol (Ppm) to 1100: 90 to 110, and most preferably 10: 1000: 100, and the mixture contains the dandelion root extract, the caffeine And tocopherol.

In the present invention, the above-mentioned composition for external application for skin, preferably a pharmaceutical composition and a cosmetic composition for enhancing skin moisturizing power, skin barrier strengthening, skin aging, skin turnover promotion or skin antioxidation, , 0.000003 to 40% by weight, more preferably 0.00003 to 30% by weight, and most preferably 0.1 to 10% by weight of a mixture of caffeine and tocopherol.

In the present invention, the composition comprising a mixture of the above-mentioned Dandelion root extract, caffeine and tocopherol is preferably selected from the group consisting of dandelion root extract, If the total content of the mixture of caffeine and tocopherol is less than 0.000003% by weight, it is too low to be effective as an external preparation. If the content of the mixture of dandelion root extract, caffeine and tocopherol in the composition is higher than 40% by weight, There is a fear of skin safety and can not be dissolved, so that it is impossible to formulate during the formulation.

In the present invention, the tocopherol may be at least one selected from the group consisting of? -Tocopherol,? -Tocopherol,? -Tocopherol and? -Tocopherol.

In the present invention, the composition may be characterized by decreasing the expression level of a gene encoding CLDN4 (Claudin 4).

The pharmaceutical composition comprising a mixture of the above-mentioned Dandelion root extract, caffeine and tocopherol may be used as a preservative, a stabilizer, a wetting agent or an emulsifying accelerator, a pharmaceutical adjuvant such as a salt for controlling osmotic pressure and / or a buffer, ), An excipient, a diluent, etc.), and may be formulated in the form of a parenteral administration (coating agent) according to a conventional method.

The term " carrier " is defined as a compound that facilitates the addition of a compound into a cell or tissue. For example, dimethylsulfoxide (DMSO) is a commonly used carrier that facilitates the introduction of many organic compounds into cells or tissues of an organism.

The term " excipient " refers to a substance which, when used in tablets or pills, is added to the medicine to make it easier to eat or to have a certain color and shape when the amount of the drug is low. Lactose or starch is mainly used do.

The term " diluent " is defined as a compound that not only stabilizes the biologically active form of the compound of interest, but also dilutes in water to which the compound is dissolved. Salts dissolved in buffer solutions are used as diluents in the art. A commonly used buffer solution is phosphate buffered saline, since it mimics the salt state of the human solution. Since buffer salts can control the pH of the solution at low concentrations, buffer diluents rarely modify the biological activity of the compounds.

The composition comprising a mixture of the above Dandelion root extract, caffeine and tocopherol is a medicinal composition which is mixed with other active ingredients as such or in combination therapy with a suitable carrier or excipient, ).

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

The parenteral administration (coating) may be, for example, an injection, an ointment, an ointment, a lotion, a gel, a cream, a spray, a suspending agent, an emulsion, a suppository, But is not limited thereto.

The pharmaceutical composition according to an embodiment of the present invention may be administered (applied) by parenteral, rectal, topical, transdermal, or the like. The pharmaceutical composition according to one embodiment of the present invention may be administered topically to the scalp, for example.

In addition, the pharmaceutically acceptable dose, that is, the dosage (amount) of the active ingredient may be appropriately determined depending on the age, sex, and weight of the subject to be treated, the specific disease or pathological condition to be treated, the severity of the disease or pathological condition, ) And the judgment of the prescriber. Determination of the dosage based on these factors is within the level of ordinary skill in the art. The dosage (amount of application) is, for example, 0.01 to 5000 mg, preferably 0.1 to 2000 mg, more preferably 0.5 to 500 mg, and most preferably 1 to 100 mg per kg of body weight per day (Application), but the dose (application amount) does not limit the scope of the present invention by any means.

Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredients, including a mixture of dandelion root extract, caffeine and tocopherol, are contained in an amount effective to achieve its intended purpose. More specifically, a therapeutically effective amount refers to an amount of a compound that is effective to prolong the survival of an object to be treated or to prevent, alleviate, or alleviate symptoms of the disease. The determination of a therapeutically effective amount is well within the ability of those skilled in the art, particularly in light of the detailed disclosure provided herein.

A therapeutically effective amount of a dandelion root extract, a mixture of caffeine and tocopherol, and a composition (compounds) comprising it as an active ingredient used in the methods of the present invention can be measured early from the cell culture assay. For example, a dose can be calculated in an animal model to obtain a circulating concentration range that includes IC ₅₀ (half maximal inhibitory concentration) or EC ₅₀ (half maximal effective concentration) determined in cell culture. Such information can be used to more accurately determine useful doses in humans.

The toxicity and therapeutic efficacy of a mixture of dandelion root extract, caffeine and tocopherol as described herein, or compositions (compounds) comprising it as an active ingredient can be determined, for example, by the LD ₅₀ (lethal dose to 50% In order to determine the ED ₅₀ (the dose having a therapeutic effect on 50% of the population), IC ₅₀ (the dose with therapeutic inhibition effect on 50% of the population), by cell culture or by surface restriction procedures in laboratory animals Can be estimated. The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the ratio between LD ₅₀ and ED ₅₀ (or IC ₅₀ ). Compounds with a high therapeutic index are preferred. Data from these cell culture assays can be used to estimate the range of doses used in humans. The dosage or amount of such compounds is preferably within the range of circulating concentrations, including the ED ₅₀ (or IC ₅₀ ), with no or little toxicity.

In the present invention, it is preferable that the pharmaceutical composition is any one selected from the group consisting of ointments, lotions, gels, creams, sprays, suspensions, emulsions, and patches. When the composition according to the present invention is applied to a pharmaceutical composition, it may be formulated into a solid, semi-solid or liquid form by adding an inorganic or organic carrier to the composition as an active ingredient. The active ingredient of the present invention can be easily formulated according to the conventional method, and can be easily formulated by adding a surfactant, an excipient, a colorant, a spice, a stabilizer, an antiseptic, a preservative, a wetting agent, an emulsification accelerator, Buffers, and other adjuvants that are commonly used.

In the present invention, the cosmetic composition comprising a mixture of dandelion root extract, caffeine and tocopherol is a composition for external application for skin, which can be used as a composition for softening the skin, a cosmetic lotion, a nourishing lotion, a lotion, an eye cream, a nutrition cream, a massage cream, a cleansing cream, , A cleansing water, a powder, an essence, and a pack.

In addition, the composition comprising the mixture of dandelion root extract, caffeine and tocopherol according to the present invention can be used as a moisturizer (polyol or the like), a viscosity regulator, an aging agent, a pH adjuster, a fat, an organic solvent, a solubilizing agent, a thickening agent, A surfactant, a water, an ionic emulsifier, a nonionic emulsifier, a filler, a sequestering agent, a chelating agent, a preservative, a vitamin, a wetting agent, an oil, an antioxidant, a suspending agent, a stabilizer, a foaming agent, May contain auxiliary agents commonly used in the fields of medicine, pharmacy, cosmetics or dermatology, such as dyes, pigments, hydrophilic active agents, lipophilic active agents, lipid vesicles, or any other ingredient commonly used in pharmaceuticals and cosmetics. Such adjuvants are introduced in amounts commonly used in the fields of medicine, pharmacy, cosmetics or dermatology. In addition, the composition of the present invention may contain a skin absorption promoting substance to increase the skin condition improving effect.

The 'polyol' contained in the composition of the present invention may mean a polyhydric alcohol, that is, an aliphatic compound having two or more hydroxyl groups (-OH). The one having two hydroxyl groups is called glycol or diol, the one having three hydroxyl groups is called glycerol and the one having four hydroxyl groups is called pentaerythritol.

According to a preferred embodiment of the present invention, the polyol is selected from the group consisting of sorbitol, polyethylene glycol, polypropylene glycol, dipropylene glycol, propylene glycol, 1,3- Butene glycol, glycerin, glycerol, propanediol, ethyl hexanediol, 1,2-hexanediol, and phage / Polybutylene glycol-8/5/3 glycerin and pentylene glycol, more preferably glycerin (glycerin), glycerin , Propylene glycol, ethylhexanediol, propanediol, 1,3-butylene glycol, sorbitol and polyethylene glycol, and most preferably selected from the group comprising glycerin, propylene glycol, butylene glycol, dipropylene glycol, and polyethylene glycol To It may be selected from the group hereinafter.

The polyol contained in the composition is contained in an amount of 1 to 20% by weight, and when the content of the polyol component is less than 1% by weight, the emulsifying power and moisture retention are poor. When the content of the polyol component is more than 20% by weight, It can fall.

In the present invention, the oil may be at least one selected from the group consisting of a hydrocarbon-based oil, a higher fatty acid-based oil, an ester-based oil and a glyceride-based oil, but is not limited thereto.

The oil may be, for example, a hydrocarbon-based oil selected from squalane, polybutene, polyisobutene, polydecene, and hydrogenated polydecene; Higher fatty acid-based oils selected from cetyl alcohol, stearyl alcohol, behenyl alcohol, 2-octyldodecanol and isocetyl alcohol; Isopropyl palmitate, isopropyl palmitate, 2-octyldodecyl myristate, isopropyl myristate, butyl octyl salicylate, cetyl octanoate, cetyl octyl hexanoate, coco caprylate / caprate, decyl cocoate, Ester-based oils in which the aryl is selected from the group consisting of saxate, pentaerythritol tetrahexylhexanoate, and dicaprylyl carbonate; And caprylic / capric triglyceride, and the like; And the like.

The oil is contained in an amount of 5 to 10% by weight based on the total weight of the composition. If the content of the oil is less than or more than the above range, the stability of the composition is lowered and it is difficult to produce various cosmetic products

In the present invention, the viscosity adjusting agent acts to increase the viscosity of the cosmetic material, thereby facilitating the application of the cosmetic material, thereby further enhancing the effect of tightness, tightness, and tightness on the skin.

The viscosity controlling agent used in the present invention may be, for example, polyvinyl alcohol, hydroxyethyl acrylate-sodium acryloyldimethyltaurate copolymer, carboxyvinyl polymer, pectin, sodium alginate, carboxymethylcellulose, hydroxyethylcellulose , Polyacrylic acid, alkyl acrylic acid-acrylic acid copolymer, and xanthan gum, but is not limited thereto.

The thickener used in the present invention means a substance which increases the viscosity, and among them, the oil thickener means an increasing agent mainly composed of oil. The oil thickener includes sucrose esters, alkyl rosinates, dextrin esters, or polyglyceryl esters. More specifically, the oil thickener is selected from the group consisting of dimer dilinoleyl hydrogenated rosinate, phytosteryl / isostearyl / cetyl / stearyl / benzyl dimer dirinolate (pytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate, polyglyceryl-10-dodecabehenate, sucrose oleate, sucrose tetrastearate triacetate, glyceryl / polyglyceryl Polyglyceryl-6-isostearate / behenate esters, dextrin palmitate / ethylhexanoate, dextrin myristate, glyceryl behenate / Glyceryl behenate / eicosadioate, and hydrogenated rosine. In the group consisting of glyceryl behenate / eicosadioate and hydrogenated rosin, Which include one or more.

Among the chelating agents, disodium EDTA is a function to prevent the metal ions from bonding with metal ions and to prevent the metal ions from being mixed with components used in the manufacture of medicines or cosmetics, Thereby preventing quality deterioration and rancidity of medicines or cosmetics. It also acts as an accelerator to help effective skin absorption of active ingredients. It is preferable that the disodium iodide is contained in the range of 0.01 to 0.5% by weight in the pharmaceutical composition or cosmetic composition.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Manufacturing example : Manufacture of a mixture of dandelion root extract, caffeine and tocopherol

Preparation of Dandelion Root Extract : Dandelion roots were screened and pulverized, and then extracted with hot water extraction method for about 4 hours using purified water having a volume (w / v) of about 7 times the weight of the pulverized material as a solvent, Purified water is added to extract second. The extract was immediately filtered and concentrated in vacuo, mixed with dextrin 1: 1, spray dried or lyophilized to obtain dandelion root extract.

First, a mixture of a sample (Dandelion root extract, caffeine or tocopherol), a mixture of two samples (a mixture of dandelion root extract and caffeine, a mixture of dandelion root extract and tocopherol or a mixture of caffeine and tocopherol) (Mixture of dandelion root extract, caffeine and tocopherol) was prepared. The mixture of the three samples contained dandelion root extract, caffeine and tocopherol in a concentration of 8-12: 800-1200: A mixture in the range of 80 to 120, or a mixture in the range of 9 to 11: 900 to 1100: 90 to 110. Then, one sample or two or three kinds of mixtures were prepared in the composition shown in Table 1 below.

Configuration Concentration (ppm) Mixing ratio Example 1 Dandelion root extract 10 One Caffeine 1000 100 Tocopherol 100 10 Comparative Example 1 Dandelion root extract 100 One Caffeine 1000 10 Tocopherol 100 One Comparative Example 2 Dandelion root extract 1000 10 Caffeine 1000 10 Tocopherol 100 One Comparative Example 3 Dandelion root extract 10 One Caffeine 10 One Tocopherol 10 One Comparative Example 4 Dandelion root extract 100 One Caffeine 100 One Tocopherol 100 One Comparative Example 5 Dandelion root extract 1000 One Caffeine 1000 One Tocopherol 1000 One Comparative Example 6 Dandelion root extract 10 Single processing Comparative Example 7 Dandelion root extract 100 Single processing Comparative Example 8 Dandelion root extract 1000 Single processing Comparative Example 9 Caffeine 10 Single processing Comparative Example 10 Caffeine 100 Single processing Comparative Example 11 Caffeine 1000 Single processing Comparative Example 12 Tocopherol 10 Single processing Comparative Example 13 Tocopherol 100 Single processing Comparative Example 14 Tocopherol 1000 Single processing Comparative Example 15 Dandelion root extract 10 One Caffeine 1000 100 Comparative Example 16 Dandelion root extract 10 One Tocopherol 100 10 Comparative Example 17 Caffeine 1000 10 Tocopherol 100 One

The caffeine and tocopherol used in the present invention can use a variety of known products, and the tocopherol used in the present invention is delta tocopherol, which is a trade name of the manufacturer SIGMA.

Experimental Example  One: Antioxidant capacity test of mixture of dandelion root extract, caffeine and tocopherol

(1,1-diphenyl-2-picryl hydrazyl) assay, which is a method for measuring antioxidative activity against a mixture of dandelion root extract, caffeine and tocopherol, Respectively.

DPPH Assay : Mixture of dandelion root extract, caffeine and tocopherol in the range of 8 to 12: 800 to 1200: 80 to 120, ppm to 9: 11: 900 to 1100: 90 to 110 In order to examine the antioxidant effect of the mixture, Example 1 and Comparative Examples 1 to 17, DPPH oxidation inhibitory effect was measured by the change of absorbance generated by reduction of the free radical DPPH (oxidation of the antioxidant) (Positive control: Vit C, an antioxidant).

Specifically, a mixture prepared by mixing 190 μl of a 100 μM DPPH solution (using ethanol as a solvent) in the range of 8 to 12: 800 to 1200: 80 to 120, and 9 to 11: 900 to 1100: 90 to 110 , Example 1, Comparative Example 1 to 17, or Positive control group was added to each well, and the reaction solution was reacted at 37 ° C for 30 minutes and absorbance was measured at 540 nm. IC ₅₀ means the concentration of the sample when the absorbance is reduced by 50% by the added sample.

First, as shown in FIG. 1, the antioxidant activity of Dandelion Root Extract was measured in a concentration range of 0 to 500 ppm. As a result, it was confirmed that the antioxidant activity was increased (DPPH activity decreased) in proportion to the ppm concentration of Dandelion Root Extract . In addition, the antioxidant activity of dandelion root extracts was significantly higher than that of each of the extracts derived from dandelion outposts, flowers, leaves and stems (data not shown).

Next, as shown in the above production example, the antioxidative ability of dandelion root extract: caffeine: tocopherol was varied according to the concentration of ppm.

As a result, a mixture of a sample (dandelion root extract, caffeine or tocopherol) or a mixture of two samples (mixture of dandelion root extract and caffeine, mixture of dandelion root extract and tocopherol, or mixture of caffeine and tocopherol) The mixture of three samples (dandelion root extract, mixture of caffeine and tocopherol) showed the lowest IC ₅₀ value and the highest antioxidant power. Concretely, when the dandelion root extract, caffeine and tocopherol were mixed in a concentration of 8-12: 800-1200: 80-120 on the basis of ppm concentration, the IC ₅₀ value was low and high antioxidant power , And it was confirmed that when the dandelion root extract, caffeine and tocopherol were mixed at a concentration of 9 to 11: 900 to 1100: 90 to 110 in terms of ppm concentration, the IC ₅₀ value was lower and they had higher antioxidant power. Especially, when the concentration of Dandelion Root Extract: Caffeine: Tocopherol was 10: 1000: 100, the lowest IC ₅₀ value was found to have the highest antioxidant power.

Next, a mixture (Example 1: 100% treated concentration) prepared in a mixing ratio of dandelion root extract: caffeine: tocopherol = 10: 1000: 100 and a dilution thereof (1.5625 to 50 % Treatment concentration).

As a result, as shown in FIG. 2, the antioxidant power was increased (DPPH activity was reduced by 20 to 80%) in proportion to the treatment concentration range: (i) 1.5625 to 12.5% (Iii) the treatment concentration required to reduce the DPPH activity by 50% was 5.5% (IC ₅₀ (%)). = 5.5%).

As a result, the mixture of dandelion root extract, caffeine and tocopherol according to the present invention has not only high antioxidative effect but also antioxidant ability which reduces the activity of active oxygen which is a main cause of skin aging, It is expected that there will be an effect to exert.

Experimental Example  2: Verification test of skin barrier strengthening effect of mixture of dandelion root extract, caffeine and tocopherol

The skin barrier enhancement effect of a mixture of dandelion root extract, caffeine and tocopherol was confirmed by measuring the mRNA expression level of CLDN4 (Claudin 4) involved in the formation of tight junctions (Tight Junction, TJ).

Specifically, the mixture (100% treated concentration) and its diluted solution (12.5 to 50% treated concentration) prepared in the mixing ratio of the dandelion root extract of Example 1: caffeine: tocopherol = 10: 1000: The skin barrier enhancement effect was compared by measuring the mRNA expression level of CLDN4 involved in TJ formation of keratinocytes.

Measurement of expression level of CLDN4 : Human keratinocyte HaCaT cells were cultured in a 60 mm cell culture dish using DMEM medium containing 10% fetal bovine serum (FBS) at 1.25 × 10 ⁶ cells / dish , And cultured at 37 ° C in a 5% CO ₂ incubator until confluency of 80% was reached. Then, the mixture was cultured at a mixing ratio of dandelion root extract: caffeine: tocopherol = 10: 1000: 100 After incubation, the medium was removed and 1 ml of Trizol (Invitrogen) was added to separate the RNA according to the RNA isolation method of Invitrogen. . RNA was quantitated at 260 nm using an ultraviolet detector (HEWLETT PACKARD), and RT-PCR (Reverse Transcription-Polymerase Chain Reaction) was performed. In order to analyze the relative expression pattern of each sample, the amount of mRNA expression of RPLP0 (60S acidic ribosomal protein P0) was corrected based on the expression level.

 As a result, as shown in FIG. 3, (i) the amount of CLDN4 mRNA expression was increased in proportion to the treatment concentration in the treatment concentration range of 12.5 to 100%, and (ii) the amount of CLDN4 mRNA expression 2-fold increase.

As a result, the mixture of dandelion root extract, caffeine and tocopherol according to the present invention exhibits an effect of enhancing the skin barrier function by promoting tight junction (TJ) formation by increasing the expression amount of CLDN4 in skin cells (HaCaT) Strengthening the barrier function of the skin may reduce the moisture loss of the skin, thereby increasing the moisturizing effect of the skin.

Skin aging, on the other hand, is known to occur due to a decrease in the content of extracellular matrix components such as collagen, elastin, and hyaluronic acid present in the skin. However, skin aging is accompanied by a decrease in skin moisture And CLNDN-related proteins involved in the formation of tight junctions (TJs) and OCLN (occludin) have been found to be involved in skin regeneration. Therefore, the dandelion root extract, caffeine And tocopherol may have the effect of enhancing skin barrier, preventing skin moisture loss and promoting skin anti-aging by promoting skin turnover (skin regeneration, wound healing, etc.) (Bazzoni et al. , J Cell Biol . , 156 (6): 947-9. 2002; Furuse et al. , J Cell Biol . , 156 (6): 1099-111, 2002; Nakajima et al. , J Pharmacol Exp Ther . , 354 (3): 440-7, 2015; Volksdorf et al., Am J Pathol ., 187 (6): 1301-1312,1207; Papakonstantinou et al. , Dermatoendocrinol. , 4 (3): 253-8, 2012).

The composition for external application for skin comprising the mixture of dandelion root extract, caffeine and tocopherol as an active ingredient according to the present invention can be manufactured into various formulations (medicines, cosmetics, etc.), and the functionality, cost and other conditions And can be controlled by an appropriate content ratio.

Formulation Example  1: Manufacture of ointment

The ointments containing a mixture of dandelion root extract, caffeine and tocopherol according to the present invention were prepared by mixing the ingredients of Table 2, which comprised an oily component and an aqueous component.

Compounding ingredient Content (% by weight) Purified water Balance
Dandelion root extract, mixture of caffeine and tocopherol 10.0 Caprine / capryl triglyceride 10.0
Liquid paraffin 10.0
Sorbitan sesquioleate 6.0
Octyldodec-25 9.0
Cetyl ethyl hexanoate 10.0
Squalane 1.0
Salicylic acid 1.0
glycerin 15.0
Sorbitol 10.0

Formulation Example  2: Nourishing lotion ( Milk lotion )

The ingredients of Table 3 containing the oily and aqueous components were mixed to produce a nutritional lotion comprising a mixture of dandelion root extract, caffeine and tocopherol according to the present invention.

Compounding ingredient Content (% by weight) Purified water Balance Dandelion root extract, mixture of caffeine and tocopherol 0.1 Wax 4.0 Polysorbate 60 1.5 Sorbitan sesquioleate 1.5 Liquid paraffin 0.5 Montana 202 (Manufacturer: Seppic) 5.0 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxyvinyl polymer 0.1 Triethanolamine 0.2 Preservative, coloring, fragrance Suitable amount

Formulation Example  3: Manufacture of massage cream

The ingredients of Table 4 containing the oily and aqueous components were mixed to produce a massage cream comprising a mixture of dandelion root extract, caffeine and tocopherol according to the present invention.

Compounding ingredient Content (% by weight) Purified water Balance Dandelion root extract, mixture of caffeine and tocopherol 0.1 Wax 10.0 Polysorbate 60 1.5 Piggy 60 hardened castor oil 2.0 Sorbitan sesquioleate 0.8 Liquid paraffin 40.0 Squalane 5.0 Montana 202 (Manufacturer: Seppic) 4.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservative, coloring, fragrance Suitable amount

Formulation Example  4: Manufacture of pack

The ingredients of Table 5 containing the oily and aqueous components were mixed to produce a pack containing a mixture of dandelion root extract, caffeine and tocopherol according to the present invention.

Compounding ingredient Content (% by weight) Purified water Balance Dandelion root extract, mixture of caffeine and tocopherol 0.1 Polyvinyl alcohol 13.0 Sodium carboxymethylcellulose 0.2 glycerin 5.0 Allantoin 0.1 ethanol 6.0 Pingyi-12 nonylphenyl ether 0.3 Polysorbate 60 0.3 Preservative, coloring, fragrance Suitable amount

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

Claims (8)

A dandelion root extract, a mixture of caffeine and tocopherol as an active ingredient.
The composition for external application for skin according to claim 1, wherein the composition is for enhancing skin barrier, enhancing skin moisturizing power, promoting skin turnover, skin antioxidation or skin anti-aging.
The composition for external application for skin according to claim 1, wherein the mixture is a mixture of dandelion root extract, caffeine and tocopherol in a mixing ratio of 8 to 12: 800 to 1200: 80 to 120 on a ppm basis.
4. The composition for external application for skin according to claim 3, wherein the mixture is a mixture of dandelion root extract, caffeine and tocopherol in a mixing ratio of 10: 1000: 100 on a ppm basis.
The external preparation for skin according to claim 1, wherein the tocopherol is at least one selected from the group consisting of? -Tocopherol,? -Tocopherol,? -Tocopherol and? -Tocopherol.
The composition for external application for skin according to claim 1, wherein the composition reduces the expression level of a gene encoding CLDN4 (Claudin 4) of skin cells.
The composition for external application for skin according to claim 1, wherein the content of the mixture is 0.000003 to 40% by weight.
The composition for external application for skin according to claim 1, wherein the composition is a pharmaceutical composition or a cosmetic composition.

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