KR102370802B1 - 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 composition for external application for skin comprising a mixture of dandelion root extract, caffeine and tocopherol, and more particularly, to skin barrier strengthening, skin moisturizing power enhancement, skin turnover comprising dandelion root extract, caffeine and tocopherol as active ingredients It relates to a composition for external application for skin for promotion, 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 manufacturing pharmaceuticals and cosmetics having skin barrier strengthening, skin moisturizing power enhancement, skin turnover promotion, skin antioxidant or skin anti-aging function. .

Description

External Composition for Skin Containing the Mixture of the Root Extract of Taraxacum officinale, 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 skin barrier strengthening, skin moisturizing power enhancement, skin turnover comprising dandelion root extract, caffeine and tocopherol as active ingredients It relates to a composition for external application for skin for promotion, skin antioxidant, or skin anti-aging.

The most important function of the epidermis, which is located in the outermost part of the skin, is to protect the skin from various external stimuli (chemicals, air pollutants, dry environment, physical and chemical irritants such as UV rays) and protect the skin. It is a protective function that prevents excessive leakage of body moisture through the body, and this protective function can only be maintained when the stratum corneum composed of keratinocytes is normally formed. The stratum corneum (horney layer), which is the outermost of the epidermis, is formed from keratinocytes, and is composed of keratinocytes with complete differentiation and a lipid layer surrounding them (Elias, J. Invest. Dermatol ., 80:44). -49, 1983). Keratinocytes are characteristic cells in which basal cells, which continuously proliferate in the lowermost layer of the epidermis, undergo morphological and functional changes in stages, and rise to the surface of the skin. It is eliminated and new keratinocytes take over their functions, and this repetitive series of changes is called “differentiation of epidermal cells” or “keratinization”. During the keratinization process, keratinocytes form the stratum corneum while generating Natural Moisturizing Factor (NMF) and intercellular lipids (ceramide, cholesterol, fatty acids), and the stratum corneum has firmness and flexibility to form the skin barrier. ) to retain its function.

However, the stratum corneum can easily lose its function due to excessive washing, lifestyle factors such as bathing, environmental factors such as dry air and pollutants, and intrinsic diseases such as atopic skin or aged skin. Due to the increasing number of factors in recent years, the number of people complaining of dry skin symptoms and various disorders is increasing. Therefore, many studies have been conducted to supply moisture from the outside in order to maintain proper skin moisture or to prevent moisture loss from the body. It is widely used in the field.

As the number of harmful factors to humans increases in the living environment and the aging population rapidly increases, the stratum corneum formation-turnover rate is slowed, the lipid synthesis ability of keratinocytes is reduced, or normal cells in the epidermis are reduced. Because division, maturation, and differentiation are not smooth, the amount of moisturizing factors and lipids in the stratum corneum is reduced, and the number of humans with skin in a state in which the skin barrier function is disrupted is gradually increasing. is in trend

Due to the division and differentiation of these abnormal epidermal cells, the skin causes various skin diseases such as dry skin, atopic dermatitis and psoriasis. However, it is difficult to expect a fundamental cure.

In general, sebum in the skin, including the scalp and face, plays a role in maintaining moisture in the skin and preventing the invasion of microorganisms. A number of diseases, such as

As human skin ages, it undergoes changes due to various internal and external factors. That is, internally, the secretion of various hormones that control metabolism is reduced, the function and activity of immune cells are lowered, so the biosynthesis of immune proteins and biological constituent proteins necessary for the living body is reduced, and externally, due to the destruction of the ozone layer, Due to this, the content of ultraviolet rays reaching the surface of the sun increases and as the environmental pollution intensifies, free radicals and active free radicals increase, thereby reducing the thickness of the skin, increasing wrinkles, and decreasing elasticity. The complexion of the skin also becomes dull, skin troubles occur frequently, and various changes such as freckles, freckles and age spots increase.

As aging progresses, the content and arrangement of collagen, elastin, hyaluronic acid, and glycoproteins, which are substances constituting the skin, change or decrease, symptoms appear, and oxidative stress is caused by free radicals and free radicals and free radicals. In addition, cyclooxygenase-2 (Cox-2, cyclooxygenase), an enzyme that produces proinflammatory cytokines known to cause inflammation, in most cells constituting the skin due to aging or UV rays ) increases, the biosynthesis of matrix metalloproteinase (MMP), an enzyme that decomposes skin tissue by these inflammatory factors, increases, and NO (nitric oxide) production by iNOS (inducible nitric oxide synthase) is known to increase.

That is, the biosynthesis of matrix materials is reduced by the decrease in cell activity and micro-inflammation according to the naturally occurring endogenous aging, and external factors such as the increase in stress caused by various harmful environments and the increase in reactive oxygen species by sunlight As the decomposition and degeneration is accelerated, the skin matrix is destroyed and thinned, and various symptoms of skin aging appear. Therefore, it is a reality that many studies are being conducted on active ingredients that can prevent and improve these aging phenomena.

Research on antioxidants started with the discovery of SOD (superoxide dismutase), an enzyme that scavenges superoxide radicals by McCord and Fridovich in 1969. As I became interested in it, it started in earnest.

Free radicals such as superoxide are produced in the body by external stress, ultraviolet rays, smoking, drugs, and free radicals, and have non-selective and irreversible destructive action on cellular components such as lipids, proteins, sugars, and nucleic acids (eg, DNA). It is known to cause various diseases such as aging, cancer, brain diseases such as stroke and Parkinson's disease, heart disease, ischemia, arteriosclerosis, skin diseases, digestive diseases, inflammation, rheumatism, and autoimmune diseases. In this way, free radicals cause various functional disorders due to oxidative destruction of cells, thereby causing aging and diseases.

Recently, as it has been revealed that active oxygen and superoxide act as direct causes of various diseases and aging, antioxidant research is shifting from research on the development of antioxidants as food additives to research on antioxidants as anti-aging and disease treatment agents. .

Dandelion ( Taraxacum ) officinale , Dandelion) is a perennial herb that grows in fields or roadsides, and flowers bloom in April-May. In oriental medicine, dandelion outpost dried before flowering is called pogongyeong. It has been used as tonic, antipyretic, diuretic, gastric, expectorant, and detoxifying.

Dandelion contains ingredients such as taraxasterol, choline, inulin, and pectin, and specifically, dandelion root is taraxol, taraxenol, taraxasterol, beta-amirin, stigmasterol, choline. , organic acids, fructose, sucrose, glucose, glucoside, etc. Dandelion leaves contain rutin, violaxanthin, plastoquinone, vitamin C (50-70 mg/100 g) and vitamin D (5-9 mg/100 g). Dandelion flower contains alnidiol, rutin and flavoxanthin (Oriental Medical Dictionary, Kyunghee University Press, p514, 1999). Dandelion contains a lot of inulin, sterol, choline, palmitin, and serochin as special ingredients. In particular, linoleic acid and choline components of dandelion are known to be effective in adult diseases such as high blood pressure, heart disease, and liver disease (Kim et al. , Free radical , YeoMoonGak, Seoul, 1997).

As a study on the composition of these plants of the genus Dandelion, ρ-hydroxyphenylacetic acid, 3,4-dihydroxycinnamic acid, and melisic acid from the roots of dandelion It has been reported that many active ingredients such as , taraxasteryl acetate, taraxol, taraxerol, and ψ-taraxasterol have been isolated (Wankyun Hwang, etc., active ingredient of dandelion (I)) Ingredients, 25(3):209-213, 1994; and Hans-Willi R and Jai-tung H, Phytochemistry , 24:1557-1562, 1985). In the West, dandelion is used as a medicine for promoting bile secretion, antirheumatic, and diuretic (Yang KS and Jeon CM, Korean J. Pharmacogn. , 27:267-273, 1996), and the dried leaves and roots of dandelion are frequently used as coffee substitutes. (Jeong JY et al. , Arch. Pharm . Res. , 14:68-72, 1991), especially among polyphenol compounds, flavonoids, luteolin, cinnamic acid, coumarin, taraxasterol, and chlorophyll and vitamin C It contains a lot of (Williams CA et al. , Phytochemistry , 42:121-127, 1996).

Caffeine is a kind of alkaloid contained in the fruits, leaves, seeds, etc. of some plants such as coffee and tea. It has a xanthine structure with three methyl groups (C ₈ H ₁₀ O ₂ N ₄ ), It is a white crystal. Caffeine has a pharmacological action such as a central nervous system stimulant, a cardiac agent, a diuretic, and has an effect of decomposing fat, particularly cellulite. That is, caffeine increases the amount of cAMP by inhibiting the activity of nucleotide phosphodistase, thereby enhancing the activity of triacylglycerollipase and promoting lipolysis, so it is widely used in body line related slimming cosmetics. ingredients used. In addition, caffeine is known to play a role in removing skin cells damaged by UV in the skin.

Tocopherol, also called vitamin E, is known to be synthesized in green plants and photosynthetic bacteria. In addition, it is abundant in many vegetable oils such as soybean, wheat, corn, rice, cotton, alfalfa and nut seed oil, and also contains fruits and vegetables such as raspberries, beans, peas, fennel, peppers, etc. is known to have been In general, tocopherol exists as four homologues: alpha (α-), beta (β-), gamma (γ-) and delta (δ-). The homologues are distinguished by the number and position of methyl groups (CH ₃ ) bonded to the aromatic ring constituting the tocopherol molecule (Hess, In Antioxidants in higher plants (Alscher RG, Hess JL eds.), CRC Press, Boca Raton, FL. pp111-134, 1993)). Among them, α-tocopherol (α-tocopherol) is the most nutritionally effective vitamin E component and has the greatest bioactivity. The α-tocopherol has the highest vitamin E activity among the homologues and is known to have about 9 times higher vitamin E activity than γ-tocopherol (Machlin, In Handbook of Vitamins (Machlin LJ ed.), Marcel Dekker, New York, NY). (pp 99-150, 1991).

The substance with the action of vitamin E is tocol, that is, 2-methyl-2-[trimethyl-tridecyl]-6-hydroxychromane (2-methyl-2[tri-methyl-tridecyl]-6-hydroxychromane). ) is a chroman derivative having a basic skeleton. The side chain of tocopherol is derived from phytol, and trienol having double bonds at positions 3', 7', and 11' of the side chain has a structure similar to that of tochol. Tochols and trienols form various isomers depending on the position and number of methyl groups on the chroman ring.

Tocopherol has an antioxidant action and prevents the oxidation of vitamin A in vivo. In addition, it is also used in toothpaste to prevent periodontitis. The antioxidant activity of tocopherol isomers is superior to that of delta tocopherol in the ratio of alpha:beta:gamma:delta=1:1.3:1.8:2.7 at room temperature. Tocopherol itself is unstable, so its derivatives are often used. In particular, various types of derivatives such as vitamin acetate and vitamin palmitate exist.

Under this technical background, the present inventors made diligent efforts to develop a composition for external application for skin condition improvement, and as a result, dandelion root extract, caffeine and tocopherol rather than one or two types selected from the group consisting of dandelion root extract, caffeine and tocopherol. A composition comprising a mixture consisting of

An object of the present invention is to provide an external composition for skin comprising a mixture of dandelion root extract, caffeine and tocopherol according to the present invention as an active ingredient, preferably strengthening the skin barrier, enhancing skin moisture, promoting skin turnover, skin antioxidant and anti-skin To provide an external composition for enhancing aging efficacy.

In order to achieve the above object, the present invention provides a composition for external application to the skin comprising a mixture of dandelion root extract, caffeine, and tocopherol as an active ingredient, preferably strengthening the skin barrier, enhancing skin moisture, and turning the skin comprising the mixture as an active ingredient It provides a pharmaceutical composition and a cosmetic composition for over-promoting, anti-oxidation of the skin or anti-aging of the skin.

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 manufacturing pharmaceuticals and cosmetics having skin barrier strengthening, skin moisturizing power enhancement, skin turnover promotion, skin antioxidant or skin anti-aging function. .

1 shows a comparison of the antioxidant power of dandelion root extract with that of vitamin C (Vit C).
Figure 2 shows the antioxidant activity of a mixture of dandelion root extract, caffeine and tocopherol (ppm concentration, 10: 1000: 100).
3 shows the expression level of CLDN4 mRNA in keratinocytes by treatment with a mixture of dandelion root extract, caffeine, and tocopherol (ppm concentration, 10:1000:100).

Unless defined otherwise, 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 those well known and commonly used in the art.

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

As used herein, the term “about” used to express volume, time (period), concentration, content, area, temperature, etc. means that there is a tolerance of up to 10% in the corresponding numerical value or numerical range.

Throughout this specification, "%" used to indicate the concentration of a specific substance is (weight/weight) % for solid/solid, (weight/volume) % for solid/liquid, and Liquid/liquid is (volume/volume) %.

In an embodiment of the present invention, DPPH (1,1-diphenyl-2-picrylhydrazyl; 1,1-diphenyl -2-picryl hydrazyl) assay was confirmed. As a result, rather than one sample (dandelion root extract, caffeine or tocopherol) or 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), The mixture consisting of three samples (a mixture of dandelion root extract, caffeine and tocopherol) showed the lowest IC ₅₀ value and was confirmed to have the highest antioxidant activity. Specifically, when dandelion root extract, caffeine, and tocopherol were mixed at a ppm concentration of 8-12: 800-1200: 80-120 among the mixtures composed of the three samples, a low IC ₅₀ value was exhibited, resulting in high antioxidant power. It was confirmed that dandelion root extract, caffeine and tocopherol were mixed at a ppm concentration of 9-11: 900-1100: 90-110, and showed a lower IC ₅₀ value, confirming to have a higher antioxidant power, In particular, based on the ppm concentration, when the mixing ratio of dandelion root extract: caffeine: tocopherol was 10: 1000: 100, it showed the lowest IC ₅₀ value and was confirmed to have the highest antioxidant power (see Experimental Example 1).

In another embodiment of the present invention, based on the ppm concentration, the mixture (100% treatment concentration) and its dilution (1.5625-50% treatment concentration) prepared at a mixing ratio of dandelion root extract: caffeine: tocopherol = 10: 1000: 100 Antioxidant activity was compared. As a result, as shown in Figure 2 below, (i) 1.5625 ~ 12.5% treatment concentration range: the antioxidant power increased in proportion to the treatment concentration (reducing the DPPH activity to 20 ~ 80%), (ii) 12.5 ~ 100% treatment concentration range: The treatment concentration exceeding 12.5% did not differ from the 12.5% treatment concentration (80% decrease in DPPH activity), (iii) the treatment concentration required to reduce DPPH activity by 50% was 5.5% (IC ₅₀ = 5.5%) was confirmed (see Experimental Example 1).

In another embodiment of the present invention, the mRNA expression level of CLDN4 (Claudin 4) involved in the formation of a close junction (closed junction, tight junction, TJ) was measured for the skin barrier strengthening effect of a mixture of dandelion root extract, caffeine and tocopherol was confirmed as As a result, as shown in FIG. 3 below, (i) in the 12.5 to 100% treatment concentration range, the mRNA expression level of CLDN4 increased in proportion to the treatment concentration, and (ii) at the 100% treatment concentration, the mRNA expression level of CLDN4 was higher than that of the control group. It was confirmed that the increase was about 2 times (see Experimental Example 2).

Accordingly, in one aspect, the present invention provides a composition for external application to the skin comprising a mixture of dandelion root extract, caffeine and tocopherol as an active ingredient, and preferably includes the mixture as an active ingredient to strengthen skin barrier, enhance skin moisture, and anti-aging skin , It relates to a pharmaceutical composition and a cosmetic composition for promoting skin turnover or skin antioxidant.

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

The solvent used for preparing the dandelion root extract may be more preferably water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent 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 dandelion root to be extracted, and preferably may be 1 to 20 times the weight of the dandelion root by volume, 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. 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 may be extracted by a known natural extracting method. For example, extraction may be performed by cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, or heating extraction method, preferably extraction by hot water extraction or reflux cooling extraction method, 1 to 10 times, preferably 2 times Extraction can be repeated 7 times.

The dandelion root extract may be filtered and used as a liquid, and preferably, it may be used after being solidified through a drying process such as spray-drying or freeze-drying. More preferably, it may be dried by mixing dextrin before spray drying or freeze drying.

In the present invention, the mixture of dandelion root extract, caffeine and tocopherol contains dandelion root extract, caffeine and tocopherol based on ppm concentrations, 8-12: 800-1200: 80-120, more preferably 9: 11:900 ~1100: 90 to 110, most preferably 10: 1000: may be characterized in that it is mixed at a mixing ratio of 100, the mixture is a dandelion root extract, caffeine in a weight ratio (wt%) corresponding to the mixing ratio of the ppm concentration and tocopherol may be mixed.

In the present invention, the composition for external application for skin, preferably the pharmaceutical composition and cosmetic composition for skin moisturizing, skin barrier strengthening, skin anti-aging, skin turnover promotion, or skin antioxidant comprising the mixture as an active ingredient, is a dandelion root extract , Caffeine and a mixture of tocopherol 0.000003 to 40% by weight, more preferably 0.00003 to 30% by weight, most preferably 0.1 to 10% by weight can be characterized as comprising.

In the present invention, the composition comprising a mixture of dandelion root extract, caffeine and tocopherol is formulated with a dandelion root extract, When the total content of the mixture of caffeine and tocopherol is less than 0.000003% by weight, the level is too low to have efficacy as an external application, and when the content of the mixture of dandelion root extract, caffeine and tocopherol in the composition is higher than 40% by weight, use for external application There is a concern about skin safety and it cannot be dissolved, so it is impossible to mix it in the formulation.

In the present invention, the tocopherol may be characterized in that at least one selected from the group consisting of α-tocopherol, β-tocopherol, γ-tocopherol and δ-tocopherol.

In the present invention, the composition may be characterized in that it reduces the expression level of the gene encoding CLDN4 (Claudin 4).

The pharmaceutical composition comprising a mixture of the dandelion root extract, caffeine and tocopherol is a pharmaceutical adjuvant such as a preservative, a stabilizer, a wetting or emulsifying agent, a salt and/or a buffer for regulating osmotic pressure, and other therapeutically useful substances (carriers ( base), excipients, diluents, etc.) may be additionally contained, and may be formulated in the form of parenteral administration (coating agent) according to a conventional method.

The term “carrier” is defined as a compound that facilitates the addition of the 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 living organisms.

The term "excipient" is a substance added to make the drug easier to eat or to give it a certain color and shape when the amount of the main drug is small in the preparation process of tablets or pills, and 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 subject compound, but is diluted in water which will dissolve the compound. Salts dissolved in buffer solutions are used as diluents in the art. A commonly used buffer solution is phosphate buffered saline because it mimics the salt state of human solutions. Because buffer salts can control the pH of a solution at low concentrations, buffer diluents rarely modify the biological activity of a compound.

The composition comprising a mixture of dandelion root extract, caffeine and tocopherol may be administered (application) to a human patient as such or as a pharmaceutical composition admixed with other active ingredients as in combination therapy or with suitable carriers or excipients. ) can be

Carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

In addition, the parenteral administration (coating agent) may be in the form of injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories, patches, etc., However, the present invention is not limited thereto.

The pharmaceutical composition according to an embodiment of the present invention may be administered (applied) parenterally, rectally, topically, or transdermally. The pharmaceutical composition according to an embodiment of the present invention may be locally administered (applied) to the scalp, for example.

In addition, the pharmaceutically acceptable dose of the active ingredient, that is, the dosage (application amount) is 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, the route of administration (the route of application) ) and at the discretion of the prescriber. Determination of dosage (application amount) based on these factors is within the level of one of ordinary skill in the art. The dosage (application amount) is, for example, 0.01 to 5000 mg per 1 kg of body weight per day, preferably 0.1 to 2000 mg, more preferably 0.5 to 500 mg, most preferably 1 to 100 mg per day ( It can be administered (applied) in 1 to several times so as to be applied), but the dosage (application amount) is not intended to limit the scope of the present invention in any way.

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 their intended purpose. More specifically, a therapeutically effective amount means an amount of a compound effective to prolong the survival of the subject to be treated, or to prevent, alleviate or ameliorate symptoms of a disease. Determination of a therapeutically effective amount is within the ability of one of ordinary skill in the art, particularly in light of the detailed disclosure provided herein.

The therapeutically effective amount for the dandelion root extract, the mixture of caffeine and tocopherol used in the methods of the present invention, and the composition (compounds) comprising the same as an active ingredient can be initially determined from a cell culture assay. For example, a dose can be calculated in an animal model to obtain a circulating concentration range that includes an 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 the dandelion root extract, the mixture of caffeine and tocopherol, or the composition (compounds) comprising the same as an active ingredient, described herein is, for example, LD ₅₀ (lethal dose for 50% of the population), To determine the ED ₅₀ (dose having a therapeutic effect on 50% of the population), IC ₅₀ (dose having a therapeutically inhibitory effect on 50% of the population), by cell culture or table pharmaceutical procedures in laboratory animals. can be calculated. The dose ratio between toxicity and therapeutic effect is the therapeutic index and it can be expressed as the ratio between LD ₅₀ and ED ₅₀ (or IC ₅₀ ). Compounds exhibiting high therapeutic indices are preferred. Data obtained from these cell culture assays can be used to estimate a range of doses for use in humans. The dosage or application of such compounds is preferably within a range of circulating concentrations that include the ED ₅₀ (or IC ₅₀ ) with little or no toxicity.

In the present invention, the formulation of the pharmaceutical composition is preferably 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 can be formulated in a solid, semi-solid or liquid form by adding a commercially available inorganic or organic carrier to the composition as an active ingredient. If the active ingredient of the present invention is carried out according to a conventional method, it can be formulated easily, and a surfactant, excipient, colorant, spice, stabilizer, preservative, preservative, wetting agent, emulsification accelerator, suspending agent, salt for osmotic pressure control and/or Buffers and other commercially available adjuvants may be appropriately used.

In the present invention, the cosmetic composition comprising a mixture of dandelion root extract, caffeine and tocopherol is a composition for external application to the skin, and is a softening lotion, astringent lotion, nutrient lotion, lotion, eye cream, nourishing cream, massage cream, cleansing cream, and cleansing foam. , cleansing water, powder, essence, and may be characterized in that it is formulated with any one selected from the group consisting of packs.

In addition, the composition comprising a mixture of dandelion root extract, caffeine and tocopherol according to the present invention is a moisturizing agent (polyol, etc.), a viscosity modifier, a thickener, a pH adjuster, a fat, an organic solvent, a solubilizer, a thickening agent, a gelling agent, an emollient, Antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic emulsifiers, nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, wetting agents, oils, It may contain adjuvants commonly used in the fields of medicine, pharmacy, cosmetology or dermatology, such as dyes, pigments, hydrophilic actives, lipophilic actives, lipid vesicles, or any other ingredients commonly used in pharmaceuticals and cosmetics. The adjuvant is introduced in an amount generally used in the fields of medicine, pharmaceuticals, cosmetology or dermatology. In addition, the composition of the present invention may contain a skin absorption promoting material in order to increase the skin condition improvement effect.

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

According to a preferred embodiment of the present invention, the polyol is sorbitol, polyethylene glycol, polypropylene glycol, dipropylene glycol, propylene glycol, 1,3- Butylene glycol (1,3-butylene glycol), glycerin (glycerin, glycerol), propanediol, ethyl hexanediol, 1,2-hexanediol (1,2-hexanediol), PEG / Sebum/polybutylene glycol-8/5/3 glycerin (peg/ppg/polybutylene glycol-8/5/3 glycerin) and pentylene glycol (pentylene glycol), more preferably glycerin , propylene glycol, ethylhexanediol, propanediol, 1,3-butylene glycol, sorbitol and polyethylene glycol, most preferably glycerin, propylene glycol, butylene glycol, dipropylene glycol and polyethylene glycol It can be selected from the group comprising.

The polyol included in the composition is included 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 moisturizing power are deteriorated, and when the content of the polyol component exceeds 20% by weight, the feeling of use is improved can fall

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

The oil is, 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, 2-octyldodecyl myristate, isopropyl myristate, butyl octyl salicylate, cetyl octanoate, cetyl octyl hexanoate, cococaprylate/caprate, decyl cocoate, isoste ester oil selected from aryl isostearate, pentaerythrityl tetraethyl hexanoate, and dicaprylyl carbonate; and a glyceride-based oil selected from caprylic/capric triglyceride and the like; It may be one or more selected from the like.

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

In the present invention, the viscosity modifier serves to increase the viscosity of the cosmetic to facilitate application by further enhancing the effect of tension, adhesion and tight feeling on the skin.

The viscosity modifier used in the present invention is, for example, polyvinyl alcohol, hydroxyethyl acrylate-sodium acryloyldimethyltaurate copolymer, carboxyvinyl polymer, pectin, sodium alginate, carboxymethyl cellulose, hydroxyethyl cellulose , polyacrylic acid, alkyl acrylic acid-acrylic acid copolymer, and at least one compound selected from the group consisting of xanthan gum, but is not limited thereto.

The thickener used in the present invention refers to a substance that increases viscosity, and among them, the oil thickener refers to a thickener whose main component is oil. The oil thickener includes sucrose esters, alkyl rosinates, dextrin esters, or polyglyceryl esters. More specifically, the oil thickener is dimer dilinoleyl hydrogenated rosinate, phytosteryl / isosteryl / cetyl / stearyl / benyl dimer dilinoleate (pytosteryl / isosteary / cetyl / stearyl) /behenyl dimer dilinoleate, polyglyceryl-10-dodecabehenate, sucrose oleate, sucrose tetrastearate triacetate, glyceryl/polyglyceryl -6-isostearate/behenate esters (glyceryl/polyglyceryl-6-isostearate/behenate esters), dextrin palmitate/ethylhexanoate, dextrin myristate, glyceryl behenate / Eicosadioate (glyceryl behenate/eicosadioate), and hydrogenated rosin (hydrogenated rosine) contains one or more selected from the group consisting of.

Among the chelating agents, Disodium EDTA binds to metal ions and prevents them from catalyzing their catalytic action. It blocks the activity to prevent deterioration of the quality of pharmaceuticals or cosmetics, rancidity, etc. In addition, it acts as an accelerator to help effective skin absorption of active ingredients. The disodium EDIT is preferably included in the pharmaceutical composition or cosmetic composition in an amount of 0.01 to 0.5% by weight.

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

production example : Preparation of a mixture of dandelion root extract, caffeine and tocopherol

Preparation of dandelion root extract : After selecting and pulverizing dandelion roots, extracting with hot water extraction method for about 4 hours using purified water in a volume (w/v) of about 7 times the weight of the pulverized product as a solvent, Purified water is added for secondary extraction. The extract was immediately filtered and concentrated in vacuo, mixed with dextrin 1:1, and then spray-dried or freeze-dried to obtain a dandelion root extract.

First, one sample (dandelion root extract, caffeine or tocopherol), a mixture consisting 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) and three kinds Prepare a mixture (a mixture of dandelion root extract, caffeine and tocopherol) consisting of a sample of A mixture in the range of 80 to 120, or 9 to 11: 900 to 1100: It was prepared as a mixture in the range of 90 to 110. Then, each one sample or two or three kinds of mixtures were prepared with the composition shown in Table 1 below.

composition 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 stand alone Comparative Example 7 Dandelion Root Extract 100 stand alone Comparative Example 8 Dandelion Root Extract 1000 stand alone Comparative Example 9 Caffeine 10 stand alone Comparative Example 10 Caffeine 100 stand alone Comparative Example 11 Caffeine 1000 stand alone Comparative Example 12 tocopherol 10 stand alone Comparative Example 13 tocopherol 100 stand alone Comparative Example 14 tocopherol 1000 stand alone 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

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

Experimental example One: Antioxidant activity verification experiment of a mixture consisting of dandelion root extract, caffeine and tocopherol

DPPH (1,1-diphenyl-2-picryl hydrazyl; 1,1-diphenyl-2-picryl hydrazyl) assay, a method to measure the antioxidant activity of a mixture of dandelion root extract, caffeine and tocopherol was confirmed with

DPPH Assay : Based on ppm concentration of dandelion root extract, caffeine and tocopherol, 8-12: 800-1200: A mixture of 80-120, 9-11: A mixture of 900-1100: 90-110 In order to examine the antioxidant effect of the mixture, Example 1 and Comparative Examples 1-17, the antioxidant ability by comparing and measuring the DPPH oxidation inhibitory effect through the change in absorbance generated by the reduction of DPPH, a free radical (antioxidant is oxidized) was performed (positive control group: antioxidant Vit C (Vitamin C)).

Specifically, in 190 μl of 100 μM DPPH solution (using ethanol as a solvent), 8-12: 800-1200: a mixture in the range of 80-120, 9-11: A mixture in the range of 900-1100: 90-110 , Example 1, Comparative Examples 1-17, or 10 μl each of a positive control group was added to prepare a reaction solution, and after reacting at 37° C. for 30 minutes, absorbance was measured at 540 nm. IC ₅₀ means the sample concentration when the absorbance decreases by 50% by the added sample.

First, as shown in FIG. 1, as a result of measuring the antioxidant power of the dandelion root extract in the concentration range of 0 to 500 ppm, it was confirmed that the antioxidant power increased (decreased DPPH activity) in proportion to the increase in the ppm concentration of the dandelion root extract. . In addition, it was confirmed that the dandelion root extract showed significantly higher antioxidant activity than each extract derived from the dandelion outpost, flower, leaf and stem (data not shown).

Next, as shown in Preparation Example, the antioxidant power was compared by varying the mixing ratio of dandelion root extract:caffeine:tocopherol based on the ppm concentration.

As a result, rather than one sample (dandelion root extract, caffeine or tocopherol) or 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), The mixture consisting of three samples (a mixture of dandelion root extract, caffeine and tocopherol) showed the lowest IC ₅₀ value and was confirmed to have the highest antioxidant activity. Specifically, when dandelion root extract, caffeine, and tocopherol were mixed at a ppm concentration of 8-12: 800-1200: 80-120 among the mixtures composed of the three samples, a low IC ₅₀ value was exhibited, resulting in high antioxidant power. It was confirmed that dandelion root extract, caffeine and tocopherol were mixed at a concentration of 9-11: 900-1100: 90-110 based on ppm concentration, resulting in lower IC ₅₀ values and higher antioxidant activity. In particular, based on the ppm concentration, when the mixing ratio of dandelion root extract: caffeine: tocopherol was 10: 1000: 100, it showed the lowest IC ₅₀ value and was confirmed to have the highest antioxidant power.

Next, based on the selected ppm mixing ratio, that is, based on the ppm concentration, a mixture prepared at a mixing ratio of dandelion root extract: caffeine: tocopherol = 10: 1000: 100 (Example 1: 100% treatment concentration) and a dilution thereof (1.5625-50 % treatment concentration) and the antioxidant activity was compared.

As a result, as shown in Figure 2, (i) 1.5625 ~ 12.5% treatment concentration range: the antioxidant power increased in proportion to the treatment concentration (reducing the DPPH activity by 20 ~ 80%), (ii) 12.5 ~ 100 % treatment concentration range: The treatment concentration exceeding 12.5% did not differ from the 12.5% treatment concentration (80% decrease in DPPH activity), (iii) the treatment concentration required to reduce DPPH activity by 50% was 5.5% (IC ₅₀ =5.5%) was confirmed.

After all, the mixture of dandelion root extract, caffeine and tocopherol according to the present invention has a high antioxidant effect as well as an anti-aging effect on the skin when the mixture is applied to the skin due to its antioxidant power that reduces the activity of free radicals, which is a major cause of skin aging. was judged to have the effect of exerting

Experimental example 2: A test to verify the skin barrier strengthening effect of a mixture consisting of dandelion root extract, caffeine and tocopherol

The skin barrier strengthening 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 (closed junctions, TJ).

Specifically, based on the ppm concentration, the mixture (100% treatment concentration) and its dilution (12.5-50% treatment concentration) prepared at a mixing ratio of Example 1 dandelion root extract: caffeine: tocopherol = 10: 1000: 100 The skin barrier strengthening effect was compared by measuring the mRNA expression level of CLDN4 involved in TJ formation in keratinocytes.

Method for measuring the expression level of CLDN4 : HaCaT cells, which are human keratinocytes, were placed in a 60 mm cell culture dish using DMEM medium containing 10% bovine serum (FBS) at 1.25×10 ⁶ cells/dish. After dispensing at a density of 37 ° C., 5% CO ₂ Incubated until about 80% confluency is achieved in an incubator, and then prepared at a mixing ratio of dandelion root extract: caffeine: tocopherol = 10: 1000: 100 A mixture (100% treatment concentration) or a dilution thereof (12.5-50% treatment concentration) was treated, the medium was removed, and 1 ml of Trizol (Invitrogen) was added to isolate RNA according to Invitrogen's RNA isolation method. . After RNA was quantified at 260 nm using a UV detector (HEWLETT PACKARD), RT-PCR (Reverse Transcription-Polymerase Chain Reaction) was performed. For the analysis of the relative expression pattern of each sample, the mRNA expression level of RPLP0 (60S acidic ribosomal protein P0) was corrected.

As a result, as shown in FIG. 3 , (i) in the 12.5 to 100% treatment concentration range, the mRNA expression level of CLDN4 increased in proportion to the treatment concentration, and (ii) at the 100% treatment concentration, the mRNA expression level of CLDN4 was about less than that of the control group. It was confirmed that it increased by 2 times.

After all, the mixture of dandelion root extract, caffeine and tocopherol according to the present invention increases the expression level of CLDN4 in skin cells (HaCaT) and promotes the formation of a close junction (TJ), thereby enhancing the skin barrier function, It was judged that the strengthening of the skin barrier function would also have the effect of increasing the moisturizing power of the skin by reducing the moisture loss of the skin.

On the other hand, although it is known that skin aging is caused by a decrease in the content of extracellular matrix components such as collagen, elastin, and hyaluronic acid present in the skin, when accompanied by a decrease in skin moisture content, skin aging is accelerated ( It has been reported that skin elasticity decreases, etc.), and OCLN (Occludin) and CLNDN-family proteins that are involved in forming a tight junction (TJ) have been found to be involved in skin regeneration, so the dandelion root extract according to the present invention, caffeine And it was determined that the mixture of tocopherol would also have an effect of exerting an anti-aging effect on the skin by strengthening the skin barrier, preventing skin moisture loss, and 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, 2017; Papakonstantinou et al. , Dermatoendocrinol. , 4(3):253-8, 2012).

The composition for external application for skin containing a mixture of dandelion root extract, caffeine and tocopherol according to the present invention as an active ingredient can be commercialized in various formulations (pharmaceuticals, cosmetics, etc.), taking into account the functionality, cost and other conditions of the product to be implemented Thus, it can be controlled to an appropriate content ratio.

Formulation example 1: Preparation of ointment

An ointment containing a mixture of dandelion root extract, caffeine, and tocopherol according to the present invention was prepared by mixing the ingredients in Table 2 including the oil phase component and the water phase component.

Ingredients content (wt%) Purified water remaining amount
Blend of Dandelion Root Extract, Caffeine and Tocopherols 10.0 caprin/caprylic triglyceride 10.0
liquid paraffin 10.0
Sorbitan Sesquioleate 6.0
Octyldodeces-25 9.0
Cetylethylhexanoate 10.0
squalane 1.0
salicylic acid 1.0
glycerin 15.0
sorbitol 10.0

Formulation example 2: Nutrient lotion ( milk lotion ) manufacturing

Nutrient lotion containing a mixture of dandelion root extract, caffeine, and tocopherol according to the present invention was prepared by mixing the ingredients in Table 3 including the oily component and the aqueous component.

Ingredients content (wt%) Purified water remaining amount Blend of Dandelion Root Extract, Caffeine and Tocopherols 0.1 beeswax 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 Preservatives, Colors, Flavors appropriate amount

Formulation example 3: Preparation of massage cream

A massage cream containing a mixture of dandelion root extract, caffeine, and tocopherol according to the present invention was prepared by mixing the ingredients in Table 4 including the oil phase component and the water phase component.

Ingredients content (wt%) Purified water remaining amount Blend of Dandelion Root Extract, Caffeine and Tocopherols 0.1 beeswax 10.0 Polysorbate 60 1.5 sebum 60 hydrogenated 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 Preservatives, Colors, Flavors appropriate amount

Formulation example 4: Manufacture of the pack

A pack containing a mixture of dandelion root extract, caffeine, and tocopherol according to the present invention was prepared by mixing the ingredients in Table 5 including the oil phase component and the aqueous phase component.

Ingredients content (wt%) Purified water remaining amount Blend of Dandelion Root Extract, Caffeine and Tocopherols 0.1 polyvinyl alcohol 13.0 Sodium Carboxymethyl Cellulose 0.2 glycerin 5.0 allantoin 0.1 ethanol 6.0 PINGG-12 Nonylphenyl Ether 0.3 Polysorbate 60 0.3 Preservatives, Colors, Flavors appropriate amount

As described above in detail a specific part of the present invention, for those of ordinary skill in the art, it is clear that this specific description is only a preferred embodiment, and the scope of the present invention is not limited thereby. something to do. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (8)

A composition for external application to the skin comprising a mixture of dandelion root extract, caffeine and tocopherol as active ingredients.
The composition for external application for skin according to claim 1, wherein the composition is for strengthening the skin barrier, enhancing skin moisturizing power, promoting skin turnover, skin antioxidant or skin anti-aging.
According to claim 1, wherein the mixture is dandelion root extract, caffeine and tocopherol, based on the ppm concentration, 8 to 12: 800 to 1200: characterized in that the mixture of 80 to 120, the composition for topical skin application.
The composition for external application for skin according to claim 3, wherein the mixture is a mixture of dandelion root extract, caffeine and tocopherol at a mixing ratio of 10:1000:100 based on ppm concentration.
The composition for external application for skin according to claim 1, wherein the tocopherol is at least one selected from the group consisting of α-tocopherol, β-tocopherol, γ-tocopherol and δ-tocopherol.
The composition for topical application for skin according to claim 1, wherein the composition reduces the expression level of a gene encoding CLDN4 (Claudin 4) in 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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