Promoter for production and / or activity of casein and / or VEGF-C, and external preparation for skin using same

Abstract

The present invention provides: an agent for promoting the production and / or activity of casein and / or VEGF-C, which contains a compound represented by chemical formula 1 and / or a ginseng extract containing the compound as an active ingredient; and an external preparation for the skin, which contains the agent. [Chemical Formula 1] # imgabs0 # In Chemical Formula 1, each substituent is as defined in the specification.

Description

[0001] This application is a divisional application of an application with a filing date of October 24, 2022, an application number of 2022113047829, and an invention name of "Production and / or activity promoter of fibroblast protein and / or VEGF-C and a skin topical preparation using the same". Technical Field

[0002] The present invention relates to a production and / or activity promoter of fibroin and / or VEGF-C and a skin external preparation using the promoter. Background Art

[0003] Edema is a state in which tissue fluid accumulates between tissue cells in the body. In simple terms, it is a symptom of body edema. It may be caused by heart disease, kidney disease, or poor blood circulation in any part of the body. In particular, the legs are far from the heart and are greatly affected by gravity, so the blood flow to the heart is reduced, resulting in edema. In addition, for women, edema occurs during normal pregnancy or preeclampsia. When drinking a lot of water or salt, or when tired or sleep deprived, edema may appear temporarily, but it will disappear on its own. Local edema may also occur in cases where capillary permeability increases, such as in cases of burns, trauma, local inflammation, allergic reactions, etc. In particular, leg edema is accompanied by swelling of the feet and ankles, so it is easy to detect through the feeling of tight shoes, and because the feeling of edema is accompanied by a heavy feeling in the legs, leg edema can also be detected through fatigue of the whole body. Systemic edema can be divided into cardiac, renal, hepatic, endocrine and malnutrition edema, and local edema includes edema caused by obstruction of blood vessels and lymphatic vessels and vasomotor edema. When edema occurs, the body will swell, weight will increase, eyes will swell after waking up, rings on fingers will be tight, and shoes will appear small. When pressing the shin of the calf with fingers, pitting edema (pittingedema) will also appear. It is well known that edema promotes blood circulation disorders and skin aging caused by excessive local water in the skin. In general, it is well known that skin problems will aggravate the conditions of patients with lymphedema with insufficiency and overload of the lymphatic system.

[0004] The skin is the organ that is most closely in contact with the external environment in the human body and is an important organ that protects the internal organs of the human body. The skin is mainly divided into the epidermis (epdirmis), dermis (dermis) and subcutaneous fat (hypodermis). Subcutaneous fat is composed of fat cells that form adipose tissue and store energy as fat, which is used to accumulate or release energy in the body. In other words, subcutaneous fat is stored in fat cells in the form of neutral fat when the energy supply exceeds the demand, and when the energy is exhausted, subcutaneous fat will be broken down into free fatty acids and glucose.

[0005] On the other hand, in modern society, with economic growth and improved living standards, the number of obese people has increased rapidly due to lack of exercise and high-protein diet culture, and obesity causes many diseases. Therefore, in modern society, exercise therapy, diet therapy and drug therapy are used to treat obesity.

[0006] However, for modern people with busy lives, it is difficult to expect appropriate effects of exercise therapy and diet therapy to solve obesity and obesity diseases, and once fat cells are formed, although the size can be reduced, it is impossible to remove them naturally, and there is a problem that they remain in the human body forever. Therefore, it is feasible to develop a safe skin external preparation (e.g., ointment, cosmetics, etc.) that can help decompose fat.

[0007] Therefore, the inventors completed the present invention after confirming that a specific mugwort extract as an active ingredient can promote the production or activity of reelin and / or VEGF-C (Vascular Endothelial Growth Factor-C), thereby improving edema, lymphedema, skin wrinkles and obesity. Summary of the invention

[0008] Technical issues

[0009] One embodiment aims to provide a promoter for promoting the production or activity of reelin and VEGF-C.

[0010] Another embodiment is directed to providing a skin external preparation using the enhancing agent.

[0011] Technical Solution

[0012] According to one embodiment, there is provided a production and / or activity promoter of fibroin and / or VEGF-C, which comprises, as an effective ingredient, a compound represented by the following Chemical Formula 1 and / or a ginseng extract containing the compound.

[0013] [Chemical formula 1]

[0014]

[0015] In the chemical formula 1,

[0016] X 1 is an oxygen atom or a sulfur atom,

[0017] R 1 To R 10 are each independently hydroxy or substituted or unsubstituted C1 to C20 alkyl,

[0018] n1 and n2 are each independently an integer from 0 to 4, and 1≤n1+n2≤4.

[0019] The ginseng extract may be a fermented ginseng extract.

[0020] In the chemical formula 1, R 1 is a C1 to C20 alkyl group substituted by a hydroxyl group, R 2 and R 8 are each independently a hydroxyl group, R 3 To R 7 and R 9 are each independently an unsubstituted C1 to C20 alkyl group, R 10 is a C1 to C20 alkyl group substituted with a functional group represented by the following Chemical Formula 2, n1 is an integer of 1, n3 is an integer of 3,

[0021] [Chemical formula 2]

[0022]

[0023] In the chemical formula 2,

[0024] L 1 is a substituted or unsubstituted C1 to C20 alkylene group,

[0025] R 11 and R 12 Each independently may be a hydrogen atom or a substituted or unsubstituted C1 to C20 alkyl group.

[0026] The Chemical Formula 1 may be represented by the following Chemical Formula 1-1.

[0027] [Chemical formula 1-1]

[0028]

[0029] The ginseng extract containing the compound represented by Chemical Formula 1 may be included in a concentration range of 1 μg / ml to 100 mg / ml relative to the total amount of the reticulin and / or VEGF-C production and / or activity promoter.

[0030] The compound represented by Chemical Formula 1 may be included in a concentration range of 50 nmol to 5000 nmol relative to the total amount of the reelin and / or VEGF-C production and / or activity promoter.

[0031] Another embodiment provides a skin external preparation for improving edema, lymphedema, skin wrinkles or obesity by promoting the production and / or activity of fibronectin and / or VEGF-C, characterized in that it contains the compound represented by Chemical Formula 1 and / or a ginseng extract containing the compound as an effective ingredient.

[0032] The skin external preparation is an agent for improving edema, and the edema may be caused by abnormal lymphatic vessel formation, abnormal lymphatic vessel function, or both.

[0033] The skin external preparation is an agent for improving lymphedema, which may be caused by abnormal lymphatic vessel formation, abnormal lymphatic vessel function, or both.

[0034] The skin external preparation is an agent for improving obesity, and the obesity may be caused by abnormal lymphatic vessel formation, abnormal lymphatic vessel function, or both.

[0035] Effects of the Invention

[0036] According to one embodiment, a novel ingredient may be provided that activates lymphatic function by inducing expression of reticulin and / or VEGF-C, thereby effectively preventing or controlling edema, lymphedema, wrinkle formation, or obesity. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 It is a graph showing the results of a cytotoxicity test of a fermented ginseng extract in lymphocytes.

[0038] Figure 2 It is a graph showing the results of a cytotoxicity test of a fermented ginseng extract in keratinocytes.

[0039] Figure 3 It is a graph showing the results of cytokine analysis of silylin of fermented ginseng extract in lymphocytes.

[0040] Figure 4 : is a graph showing the results of cytokine analysis of the compound represented by Chemical Formula 1-1 in lymphocytes.

[0041] Figure 5 It is a graph showing the results of VEGF-C cytokine analysis of fermented ginseng extract in keratinocytes.

[0042] Figure 6 is a graph showing the results of VEGF-C cytokine analysis of the compound represented by Chemical Formula 1-1 in keratinocytes. DETAILED DESCRIPTION

[0043] Hereinafter, the embodiments of the present invention will be described in detail so that those skilled in the art can easily implement the present invention. However, the present invention can be implemented in various ways and is not limited to the embodiments described herein.

[0044] "Reelin (RELN)" used in this specification refers to an extracellular matrix-related molecule.

[0045] In the present specification, unless otherwise specified, "substituted" or "substituted" means that at least one hydrogen atom in the functional group of the present invention is replaced by a halogen atom (F, Br, Cl or I), a hydroxyl group, a nitro group, a cyano group, an amino group (NH2, NH(R 200 ) or N(R 201 )(R 202 ), where R 200 , R 201 and R 202 The present invention is substituted with one or more substituents selected from the group consisting of an amidino group, a hydrazine group, a hydrazone group, a carboxyl group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted alicyclic organic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heterocyclic group.

[0046] In the present specification, unless otherwise specified, "alkyl" refers to C1 to C20 alkyl, specifically C1 to C15 alkyl, "cycloalkyl" refers to C3 to C20 cycloalkyl, specifically C3 to C18 cycloalkyl, "alkoxy" refers to C1 to C20 alkoxy, specifically C1 to C18 alkoxy, "aryl" refers to C6 to C20 aryl, specifically C6 to C18 aryl, "alkenyl" refers to C2 to C20 alkenyl, specifically C2 to C18 alkenyl, "alkylene" refers to C1 to C20 alkylene, specifically C1 to C18 alkylene, and "arylene" refers to C6 to C20 arylene, specifically C6 to C16 arylene.

[0047] In the present specification, unless otherwise defined, "combination" means mixing or copolymerization. In addition, "copolymerization" means block copolymerization or random copolymerization, and "copolymer" means block copolymer or random copolymer.

[0048] The skin vascular system is located in the dermis and consists of blood vessels and lymphatic vessels. In order to maintain homeostasis, the interstitial fluid that has flowed out of the blood vessels must flow back to the veins. The veins of the skin effectively transport blood to the central nervous system. However, the veins themselves lack the ability to receive interstitial fluid. Therefore, it can be seen that the tissue that receives interstitial fluid, namely the lymphatic vessels, is also an indispensable structure in the skin.

[0049] Lymphatic vessels play an important role in maintaining a constant state of the microenvironment around cells by collecting unnecessary substances in the skin or water and proteins that are constantly leaking from blood vessels. In addition, lymphatic vessels are believed to play a role in resisting infectious agents or external factors from the outside through the transport of T lymphocytes.

[0050] As a disease of lymphatic dysfunction, symptoms such as edema and lymphedema are known. In addition, the function of lymphatic vessels also plays an important role in skin photoaging (wrinkle formation) caused by ultraviolet rays, not limited to edema.

[0051] From the current research, VEGFR-3 has been identified as a transmembrane receptor that exists specifically in lymphatic vessels, and VEGF-C and VEGF-D have been found to be its ligands. VEGF-C acts on lymphatic vessels to promote the proliferation, migration and lumen formation of lymphatic endothelial cells, thereby activating lymphatic function. In addition, the possibility of gene therapy for edema, which is a pathological state of edema, is being explored by introducing VEGF-C.

[0052] In addition, in recent years, it has been known that mice with a gene mutation that causes lymphatic dysfunction develop obesity when they mature. Regarding the mechanism by which abnormal lymphatic vessel formation and function manifest obesity, it is known that lymph fluid flowing through the lymphatic vessels promotes the differentiation of precursor mast cells into fat. In other words, due to the abnormal function of the lymphatic vessels, lymph fluid leaks out of the lymphatic vessels, which leads to the differentiation of fat and, in turn, obesity. Therefore, VEGF-C promoters are also expected to be therapeutic agents for preventing obesity, which functionally induce lymphangiogenesis.

[0053] The VEGF (Vascular Endothelial Growth Factor) family genes include VEGF-A to VEGF-E. Among them, VEGF-B and VEGF-E have been identified as factors that act only on blood vessels. VEGF-A exists in the skin and acts on lymphatic vessels, but it is known to be a factor that deteriorates lymphatic vessel function.

[0054] In the skin, VEGF-D is reported to be present in trace amounts in the dermis, but since VEGF-D knockout mice do not cause abnormalities in the formation and function of skin lymphatic vessels at all, VEGF-D is not considered to be an essential factor for the formation of lymphatic vessels in the skin. On the other hand, the increase in the number of lymphatic vessels present in the dermis of mice with high expression of VEGF-C in the epidermis indicates that VEGF-C in the skin is expressed more strongly in the epidermis. In addition, neutralizing antibodies against VEGFR-3, a receptor for VEGF-C, were highly expressed in the epidermis to block the effect of VEGF-C in the epidermis, and the results showed that the number of lymphatic vessels in the dermis was extremely reduced (Makinen, T., Jussila, L., Veikkola, T., Karpanen, T., Kettunen, MI, Pulkkanen, KJ, Kauppinen, R., Jackson, DG, Kubo, H., Nishikawa, S., Yla-Herttuala, S. & Alitalo, K. (2001) Nat Med 7, 199-205). This shows that the function of lymphatic vessels in the dermis of the skin is controlled by VEGF-C expressed in the epidermis, and edema (swelling) occurs because VEGF-C does not work.

[0055] Furthermore, in recent years, various attempts have been made to control edema or swelling, improve skin aging (wrinkles), and prevent, inhibit and treat obesity by activating or strengthening the lymph or lymphatic vessels in the human body. In addition to VEGF-C, the activation or strengthening of the lymph or lymphatic vessels can also be achieved by promoting the production, differentiation and activity of fibronectin.

[0056] Therefore, the present inventors conducted a large number of experiments and repeated tests to find an effective ingredient that can improve edema, lymphedema, skin wrinkles or obesity by promoting the production or activity of fibronectin and / or VEGF-C in the human body, and finally confirmed that a composition containing a compound represented by the following chemical formula 1 that can be obtained from a ginseng extract (specifically a fermented ginseng extract) and / or a fermented ginseng extract containing the compound as an effective ingredient can function as a production and / or activity promoter of fibronectin and / or VEGF-C, thereby completing the present invention.

[0057] [Chemical formula 1]

[0058]

[0059] In the chemical formula 1,

[0060] X 1 is an oxygen atom or a sulfur atom,

[0061] R 1To R 10 are each independently hydroxy or substituted or unsubstituted C1 to C20 alkyl,

[0062] n1 and n2 are each independently an integer from 0 to 4, and 1≤n1+n2≤4.

[0063] The compound represented by Chemical Formula 1 can be obtained from fermented ginseng extracts, but cannot be obtained from unfermented (or pre-fermented) ginseng (such as fresh ginseng) extracts. After years of continuous research on the functionality of ginseng extracts, the inventors first confirmed that the productivity of fibronectin and / or VEGF-C in fermented ginseng extracts is significantly increased compared with that in unfermented ginseng extracts, and also first confirmed that by promoting the secretion of fibronectin and / or VEGF-C to activate lymphatic vessels, skin edema, etc. can ultimately be improved, thereby completing the present invention.

[0064] Although various effects of ginseng extracts are known, not all ginseng extracts are effective in preventing or controlling edema, lymphedema, wrinkle formation or obesity. So far, only attempts have been made to launch health functional foods containing a small amount of ginseng extracts (such as fresh ginseng extracts), or to use ginseng extracts for the treatment of muscle diseases or respiratory diseases. Specifically, no one knows that fermented ginseng extracts can be used as production and / or activity promoters of fibroin and / or VEGF-C.

[0065] For example, the fermented ginseng extract can be obtained by fermenting ginseng, and the ginseng is rolled and then fermented to obtain the fermented ginseng extract. That is, the fermented ginseng extract can be an extract obtained by fermenting rolled ginseng. Compared with the extract obtained by directly fermenting ginseng without performing the rolling step, the extract obtained by fermenting the rolled ginseng may be more suitable for use as a production and / or activity promoter of fibroin and / or VEGF-C. The rolling may refer to a process of repeatedly kneading ginseng and ginseng fibrous roots using physical force (destroying cell tissue and cell wall).

[0066] For example, the fermented ginseng may be ginseng fermented under anaerobic conditions. In this case, compared with ginseng fermented under aerobic conditions, it may be more suitable for use as a production and / or activity promoter of fibroin and / or VEGF-C.

[0067] For example, in the chemical formula 1, R 1 is a C1 to C20 alkyl group substituted by a hydroxyl group, R 2 and R 8 are each independently a hydroxyl group, R 3 To R 7 and R 9 are each independently an unsubstituted C1 to C20 alkyl group, R 10is a C1 to C20 alkyl group substituted with a functional group represented by the following Chemical Formula 2, n1 is an integer of 1, n3 is an integer of 3,

[0068] [Chemical formula 2]

[0069]

[0070] In the chemical formula 2,

[0071] L 1 is a substituted or unsubstituted C1 to C20 alkylene group,

[0072] R 11 and R 12 Each independently may be a hydrogen atom or a substituted or unsubstituted C1 to C20 alkyl group.

[0073] For example, the Chemical Formula 1 may be represented by the following Chemical Formula 1-1.

[0074] [Chemical formula 1-1]

[0075]

[0076] For example, the (fermented) ginseng extract containing the compound represented by Chemical Formula 1 can be included in a concentration range of 1 μg / ml to 100 mg / ml, for example, 1 μg / ml to 10 mg / ml, for example, 1 μg / ml to 1 mg / ml, for example, 1 μg / ml to 500 μg / ml, 1 μg / ml to 100 μg / ml, for example, 1 μg / ml or more and 100 μg / ml or less, 90 μg / ml or less, 80 μg / ml or less, 70 μg / ml or less, 60 μg / ml or less, 50 μg / ml or less, 40 μg / ml or less, 30 μg / ml or less, 20 μg / ml or less, for example, 1 μg / ml to 50 μg / ml, relative to the total amount of the production and / or activity promoter of the reelin and / or VEGF-C.

[0077] For example, the compound represented by Chemical Formula 1 may be included in a concentration range of 50 nmol to 5000 nmol, for example, 50 nmol or more and 5000 nmol or less, 4500 nmol or less, 4000 nmol or less, 3500 nmol or less, 3000 nmol or less, 2500 nmol or less, 2000 nmol or less, 1500 nmol or less, 1000 nmol or less, for example, 50 nmol to 2500 nmol, relative to the total amount of the production and / or activity promoter of the fibroin and / or VEGF-C.

[0078] According to one embodiment of the invention, the production and / or activity promoter of the fibroin and / or VEGF-C comprises as an effective ingredient the compound represented by chemical formula 1 and / or the (fermented) ginseng extract containing the compound and satisfies the concentration range, thereby being able to effectively promote the formation and function of lymphatic vessels. Symptoms caused by the dysfunction of lymphatic vessels include not only edema or lymphedema, but also skin photoaging (formation of wrinkles, etc.) and obesity caused by ultraviolet rays. According to one embodiment of the invention, the production and / or activity promoter of the fibroin and / or VEGF-C can effectively prevent and inhibit edema or lymphedema, skin photoaging and obesity caused by ultraviolet rays. In addition, congenital lymphedema can also be effectively treated.

[0079] Skin photoaging refers to changes in the appearance and function of the skin that generally occur with repeated exposure to sunlight. Ultraviolet rays (UV) in sunlight, especially medium-wave ultraviolet rays (called UVB, with a wavelength of 290-320nm), mainly cause photoaging. It is not clear how much UVB exposure is required to cause photoaging. However, repeated exposure to UVB that causes erythema or sunburn usually leads to photoaging. Clinically, photoaging can be specified as skin roughness, wrinkling, pigmentation, earthy color, sagging, the onset of telangiectasia, the formation of moles, the onset of purpura, easy scarring, atrophy, areas of pigment loss with fibrosis, premalignant tumors and the onset of malignant tumors. Photoaging usually occurs on skin that is habitually exposed to the sun, such as the face, ears, head, neck and hands.

[0080] According to another embodiment, a skin external preparation is provided for improving edema, lymphedema, skin wrinkles or obesity by promoting the production and / or activity of fibronectin and / or VEGF-C, characterized in that it contains the compound represented by Chemical Formula 1 and / or a (fermented) ginseng extract containing the compound as an effective ingredient.

[0081] For example, the skin external agent is an agent for improving edema, and the edema may be caused by abnormal lymphatic vessel formation, abnormal lymphatic vessel function, or both.

[0082] For example, the skin external preparation is an agent for improving lymphedema, and the lymphedema may be caused by abnormal lymphatic vessel formation, abnormal lymphatic vessel function, or both.

[0083] For example, the skin external preparation is an agent for improving obesity, and the obesity may be caused by abnormal lymphatic vessel formation, abnormal lymphatic vessel function, or both.

[0084] According to an embodiment of the skin external preparation, the dosage, application form, and dosage form can be appropriately determined according to the purpose of use. The application form of the skin external preparation is not particularly limited, and both inhalation and transdermal can be adopted. The dosage form includes, for example, perfumes, shampoos and conditioners, skin care products, shower gels, body conditioners, bath powders, air fresheners, deodorants, bath agents, lotions, creams, soaps, toothpastes, cosmetics such as aerosol products and other forms used for general fragrances. In addition, it can also be used for medicines such as inhaled drugs.

[0085] In addition, in addition to the necessary ingredients, the skin external preparation may also contain ingredients commonly used in skin external preparations such as cosmetics or medicines, such as whitening agents, moisturizers, antioxidants, oily ingredients, ultraviolet absorbers, surfactants, thickeners, alcohols, powdered ingredients, colorants, aqueous ingredients, water, various skin nutrients, etc., as needed.

[0086] In addition, metal blocking agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extract, glabridin, hot water extract of papaya fruit, various herbal medicines, tocopherol acetate, glycyrrhizic acid and its derivatives or their salts, whitening agents such as vitamin C, magnesium ascorbyl phosphate, ascorbyl glucoside, arbutin, kojic acid, sugars such as glucose, fructose, mannose, sucrose, trehalose, and vitamin A such as retinoic acid, retinol, retinyl acetate, and retinyl palmitate can also be appropriately included.

[0087] For example, the external preparation for skin may be a cosmetic composition.

[0088] In the present specification, "cosmetics" may refer to all substances having not only a beauty function but also a medical function in addition to the beauty function.

[0089] The dosage form of the cosmetic composition is not particularly limited and may be appropriately selected according to purpose.

[0090] For example, the cosmetic composition can be formulated into a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, a makeup remover containing a surfactant, oil, powder foundation, milky foundation, wax foundation, spray, etc., but is not limited thereto. More specifically, the cosmetic composition can be formulated into a cleaning agent, a tonic, a hair setting agent, a nutritional lotion, an essence, an essence milk, an oil, a conditioner, a shampoo, an emulsion, a hair care agent, or a hair dye; and basic cosmetics such as an oil-in-water (O / W) type and an oil-in-water (O / W) type. For example, the composition may have a dosage form selected from a lotion, a skin lotion, an astringent, an emulsion, a milk emulsion, a moisturizing lotion, a nourishing lotion, a massage cream, a nutrient cream, a moisturizing cream, a hand cream, an ointment, a foundation, an essence, a nourishing essence, a facial mask, a soap, a cleansing foam, a cleansing milk, a cleansing cream, a body milk, a shower gel, an emulsion, an ointment, a gel, a cream, a patch, and a spray. In addition, in each dosage form, in addition to the essential ingredients, the composition may have other ingredients that can be appropriately selected and formulated by a person skilled in the art according to the type or purpose of other external preparations. For example, ultraviolet blockers, hair conditioners, spices, etc. may also be included.

[0091] The cosmetic composition can contain a cosmetically acceptable medium or matrix. As all dosage forms suitable for local use, it can be provided as, for example, a solution, a gel, a solid or a pasty anhydrous product, an emulsion obtained by dispersing the oil phase in the aqueous phase, a suspension, a microemulsion, a microcapsule, a microparticle ball or an ionic (liposome) and / or nonionic capsule dispersion form, or a cream, a skin care water, a lotion, a powder, an ointment, a spray or a concealer stick form. These compositions can be prepared according to the conventional methods in this area.

[0092] When the dosage form of the present invention is a solution or an emulsion, a solvent, a solubilizer or a demulsifier is used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol oil, glycerol fatty esters, polyethylene glycol or fatty acid esters of sorbitol.

[0093] When the dosage form of the present invention is a suspension, as the carrier component, a liquid diluent (such as water, ethanol or propylene glycol), a suspending agent (such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitan ester and polyoxyethylene sorbitan ester), microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth gum can be used.

[0094] When the preparation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicon oxide, talc or zinc oxide etc. can be used as a carrier component.

[0095] When the dosage form of the present invention is a powder or a spray, lactose, talc, silicon oxide, aluminum hydroxide, calcium silicate or polyamide powder can be used as a carrier component. Especially when the dosage form is a spray, it can also contain a propellant such as chlorofluorocarbons, propane / butane or dimethyl ether.

[0096] In one embodiment of the present invention, the cosmetic composition may further contain a thickener. The thickener contained in the cosmetic composition of the present invention may be methylcellulose, carboxymethylcellulose, carboxymethylhydroxyguanine, hydroxymethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, polyquaternium salt, cetearyl alcohol, stearic acid, carrageenan, etc. Preferably, one or more of carboxymethylcellulose, carboxyvinyl polymer and polyquaternium salt may be used, and most preferably, carboxyvinyl polymer may be used.

[0097] In one embodiment of the present invention, as required, the cosmetic composition can contain various suitable bases and additives, and the types and amounts of these ingredients can be easily selected by the inventor. Can contain acceptable additives as required, for example, can also include conventional ingredients in this area such as preservatives, pigments, additives, etc.

[0098] The preservative may specifically be phenoxyethanol or 1,2-hexanediol, etc., and the fragrance may be an artificial fragrance, etc.

[0099] In one embodiment of the present invention, the cosmetic composition may include a composition selected from water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, sphingolipids and seaweed juice. In addition, as the formulation components that can be added, oil components, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, ethanol, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, etc. can be cited.

[0100] In addition, the components that can be added are not limited thereto, and the above-mentioned arbitrary components can be added within a range that does not impair the object and effect of the present invention.

[0101] Further, the external preparation for skin according to one embodiment may be used as a pharmaceutical composition.

[0102] Just can clearly understand the advantages and features of the present invention and the method for realizing them with reference to the embodiment described in detail below.Hereinafter, the present invention will be described in detail by embodiment.However, following embodiment is only used to describe the present invention in detail, and the scope of the present invention is not limited to following embodiment.

[0103] (Example)

[0104] Preparation Example: Preparation of Fermented Ginseng Extract and Identification of the Compound Represented by Chemical Formula 1-1

[0105] Fresh ginseng was washed 2-3 times with water, rolled for 30 minutes, cut / broken into pieces of 1-2 cm in size, sealed (50°C), and fermented under anaerobic conditions for 3 weeks. Then, it was dried with hot air at 60°C for 1 day to obtain fermented ginseng.

[0106] The fermented ginseng is placed in 50-80% EtOH and repeatedly extracted 1-3 times at 50-80° C. for 1-5 hours. The extracted sample is filtered under reduced pressure using Whatman No. 1 filter paper, and the filtered extract is concentrated using a vacuum rotary concentrator to remove the solvent component, and then purified to prepare a fermented ginseng extract.

[0107] HPLC analysis was also performed, and the presence of a compound represented by the following chemical formula 1-1 (Sigma-aldrich) in the fermented ginseng extract was confirmed by using a chromatographic column (Mightysil RP-18GP C18), a UV absorbance detector (203 nm), an injection volume (10 uL), a flow rate (1.0 mL / min), and a mobile phase (DI WATER, acetonitrile).

[0108] [Chemical formula 1-1]

[0109]

[0110] Experimental Example 1: Analysis of Cytotoxicity

[0111] (1) Human dermal lymphatic endothelial cells (HDLEC, PromoCell, Germany) were re-cultured in a 96-well culture dish for 1 day, and then treated with the fermented ginseng extract of the preparation example at concentrations ranging from 0 ppm (μg / ml) to 200 ppm (μg / ml). After culturing for 24 hours and 72 hours, the absorbance at 450 nm was measured using the QuantiMaxWST-8 cell viability assay kit to confirm the cell viability. The results are shown in Figure 1 middle.

[0112] from Figure 1 It was confirmed that the mugwort extract had no cytotoxicity within a concentration range of 200 ppm.

[0113] (2) Human keratinocytes (Normal Human Epidermal Keratinocytes; NHEK, PromoCell, Germany) were re-cultured in a 96-well culture dish for 1 day, and then treated with the fermented ginseng extract of the preparation example at concentrations of 0 ppm (μg / ml) to 200 ppm (μg / ml). After 24 hours and 72 hours, the absorbance at 450 nm was measured using the QuantiMax WST-8 cell viability assay kit to confirm the cell viability, and the results are shown in Figure 2 middle.

[0114] from Figure 2 It can be confirmed that the mugwort extract has no cytotoxicity within a concentration range of 50 ppm.

[0115] Experimental Example 2: Analysis of cytokines of fibronectin

[0116] Human lymphocytes were cultured in 6-well plates for 24 hours and then treated with DMSO as a control group (reference; (100%)), and the fermented ginseng extract of the preparation example and the compound represented by chemical formula 1-1 (Sigma-aldrich) were treated at concentrations of 1, 10, 20, 50 and 100 μg / ml and 100, 250, 500, 1000 and 2000 nmol, respectively, and cultured for 48 hours, and then the reelin cytokine was analyzed using a Human reelin ELISA kit (Mybiosource, USA) according to the instruction manual to detect the production and activity of reelin, and the results are shown in Figure 3 and Figure 4 middle.

[0117] from Figure 3 and Figure 4 It was confirmed that in the case of the compound represented by Chemical Formula 1-1 and the fermented ginseng extract containing the compound, the production and activity of fibroin can be further improved compared with the control group.

[0118] Experimental Example 3: Analysis of VEGF-C cytokine

[0119] Human keratinocytes were cultured in 6-well plates for 24 hours and then treated with DMSO as a control group (reference; (100%)), and the fermented ginseng extract of the preparation example and the compound represented by Chemical Formula 1-1 (Sigma-aldrich) were treated at concentrations of 1, 10, 20, 50 and 100 μg / ml and 100, 250, 500, 1000 and 2000 nmol, respectively, and cultured for 48 hours, and then VEGF-C cytokines were analyzed using a VEGFC Human ELISA kit (ThermoFisher, USA) according to the instruction manual, thereby detecting the production and activity of VEGF-C. The results are shown in Figure 5 and Figure 6 middle.

[0120] from Figure 5 and Figure 6 It was confirmed that in the case of the compound represented by Chemical Formula 1-1 and the fermented ginseng extract containing the compound, the production and activity of VEGF-C can be further improved compared with the control group.

[0121] Test Example 4: Preparation of external skin preparation

[0122] Cosmetic compositions useful as external skin preparations according to Example 1 and Comparative Example 1 (fresh ginseng extract; Silla University, Korea) were prepared according to the components and contents shown in Table 1. Purified water was mixed with other components so that the total amount was 100 wt %, thereby preparing cosmetic compositions.

[0123]

Table 1

[0124] (Unit: ppm)

[0125]

[0126]

[0127] 30 women aged 50 and above with edema in the lower limbs were selected, and they were asked to apply the composition according to Example 1 and Comparative Example 1 to the edematous lower limbs twice a day. After 7 consecutive days of application, each person was asked to detect i) weight change (using a weight scale), ii) change in circumference of the calf part with the most severe edema (using a plastic measuring tape), and iii) edema status (visual inspection). The results are shown in Table 2 below.

[0128]

Table 2

[0129] Example 1 Comparative Example 1 Body weight (0 day) (kg) 61 60 Body weight (7 days) (kg) 59 61 Calf circumference (0 days) (cm) 40 40 Calf circumference (7 days) (cm) 39 40 Swelling ease No change

[0130] From the above Table 2, it can be confirmed that in the case where the external preparation for skin according to one embodiment is applied, the edema state is alleviated within one week compared with the case where the external preparation for skin is not applied.

[0131] Comparison of the contents of major ginsenoside compounds between anaerobic naturally fermented ginseng extract and fresh ginseng extract Comparison

[0132] Using the anaerobic naturally fermented ginseng extract according to the preparation example and the unfermented fresh ginseng extract, HPLC analysis was performed under the same conditions to determine the content of the main ginsenoside compounds in the extract. The results are shown in Table 3 below.

[0133]

Table 3

[0134] (unit:%)

[0135]

[0136]

[0137] As can be seen from Table 3, anaerobically naturally fermented ginseng contains more of the compound represented by Formula 1-1 than other ginsenoside compounds.

[0138] Although the preferred embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements made by those skilled in the art using the basic concepts of the present invention defined in the technical solutions disclosed herein also fall within the scope of the present invention.

Claims

1. A method for preparing an anaerobic fermentation ginseng extract containing a compound represented by the following chemical formula 1-1, which is used as a production and activity promoter of fibroin and / or VEGF-C, comprising: [Chemical formula 1-1] Steps for washing fresh ginseng with water; The step of kneading the fresh ginseng; The step of cutting and crushing the fresh ginseng; The step of fermenting the fresh ginseng under anaerobic conditions; as well as The fermented fresh ginseng is dried.

2. The method according to claim 1, wherein: The anaerobic fermentation ginseng extract is contained in a concentration range of 1 μg / ml to 100 mg / ml relative to the total amount of the reelin and / or VEGF-C production and activity promoter.

3. Use of a composition comprising an anaerobic fermented ginseng extract prepared by the method of claim 1 for improving edema, lymphedema or skin wrinkles by promoting the production and activity of fibronectin and / or VEGF-C, [Chemical formula 1-1] 4. The use according to claim 3, wherein: The edema is caused by abnormal lymphatic vessel formation, abnormal lymphatic vessel function, or both.

5. The use according to claim 3, wherein: The lymphedema is caused by abnormal lymphatic vessel formation, abnormal lymphatic vessel function, or both.

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