Topical composition containing longan aril-containing crude drug extract for TLSP inhibition and treatment or improvement of skin inflammatory diseases and use thereof

Abstract

This paper relates to topical pharmaceutical and cosmetic compositions containing a mixed herbal extract of Longan, Wuhan, and Onji as active ingredients for suppressing TLSP (thymic stromal lymphopoietin) cytokine expression and treating and improving inflammatory skin diseases. [Representative diagram] Figure 1

Description

Technical Field

[0001] The present invention relates to a topical composition containing a mixed herbal medicine extract containing Longanae Arillus for TSLP suppression and treatment or improvement of skin inflammatory diseases and its use.

Background Art

[0002] Chronic relapsing dermatitis and inflammatory diseases (atopic dermatitis) such as atopic dermatitis and psoriasis have very diverse causes and are very difficult to treat.

[0003] In particular, in some patients with atopic dermatitis, the filaggrin gene is mutated, the skin barrier is damaged, and serious inflammatory reactions occur due to bacterial infections and foreign body infections derived from mites.

[0004] In addition to such genetic factors, a decrease in the water retention capacity due to a decrease in ceramide in the stratum corneum and abnormal removal of keratinocytes due to an increase in the pH of the skin surface can be factors that determine the severity of skin diseases together with skin barrier dysfunction. Furthermore, most of these skin diseases are concentrated in infancy and adolescence, causing emotional and educational social problems.

[0005] In particular, the number of scratches due to the unbearable itching associated with such skin diseases increases, further worsening the symptoms. Recently, various cytokines such as interleukin and thymic stromal lymphopoietin (TSLP) present in skin keratinocytes have been known to increase their expression, stimulate sensory nerves present under the skin, and cause itching and dermatitis (Mack et al., 2018, Trends Immunol..2018 Dec;39(12):980-991).

[0006] The inflammatory reaction is a mechanism for repairing and regenerating damaged sites when an invasion that causes any substrate change such as a physical action on organisms or tissues, contact with various chemical substances, or bacterial infection occurs.

[0007] External stimuli locally release various vasoactive substances such as inflammatory components, increasing vascular permeability and causing inflammation. In some cases, a non-uniform inflammatory response promotes mucosal damage and causes various other diseases (Willoughby DA. (1975) Human arthritis applied to animal models. Towards a better therapy. Annals of the Rheumatic Disease. 34, 471-478.).

[0008] Pro-inflammatory cytokines as inflammatory markers include tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP1), etc. (Yun HJ, Heo SK, Yi HS, Kim CH, Kim BW and Park SD. (2008) Anti-inflammatory effect of injinho-tang in Raw264.7 Cells. Kor. J. Herbology. 23(2), 169-178).

[0009] Currently, various antihistamines and steroids such as cortisone, prednisone, methylprednisolone, and dexamethasone in the form of injections or ointments are commonly used for the treatment of atopic dermatitis, but satisfactory effects have not been obtained. In particular, steroid therapy causes dilated capillaries, thinner skin layers, more severe allergic reactions, and when steroid administration is interrupted, symptoms due to steroid rebound worsen further.

[0010] Therefore, in treating and improving inflammatory skin diseases such as atopic dermatitis, there is still a need to develop more effective drugs and cosmetics with fewer side effects than conventionally used drugs from natural raw materials.

[0011] Longanae Arillus, which is the seed coat of Dimocarpus longan, Euphoria longan or the same species belonging to the Sapindaceae family, contains glucose, fructose, protein, etc., and has been reported to exhibit effects such as myocardial protection and appetite enhancement (Chung B. S et al, Dohaehyangyakdaesajeon, youngrimsa, 2nd Ed.p197-198,1998).

[0012] Ligustici Tenuissimi Rhizoma, which is the rhizome or root of Ligusticum tenuissimum Kitagawa, Ligusticum sinense Oliv, Ligusticum jeholense Nakai et Kitagawa or the same species belonging to the Umbelliferae family, contains cnidilide, 3-butylphthalide, etc., and has been reported to exhibit effects such as antibacterial effect (Chung B. S et al, Dohae-hyangyakdaesajeon, youngrimsa, 2nd Ed.P428-429,1998).

[0013] Polygalae radix, which is the root of Polygala tenuifolia Willd or the same species belonging to the Polygalaceae family, contains various saponins and has been reported to exhibit effects such as expectorant action and antibacterial action (Chung B. S et al, Dohaehyangyakdaesajeon, youngrimsa, 2nd Ed.P798-799,1998).

[0014] However, there is no report or disclosure in any of the above-mentioned documents whose disclosure content is cited and included in the present application regarding the preventive or improving activity of a locally applied mixed crude drug extract of Longanae Arillus, Ligustici Tenuissimi Rhizoma and Polygalae radix, which exhibits a strong therapeutic effect on skin inflammatory diseases.

Prior Art Documents

Non-Patent Literature

[0015]

Non-Patent Literature 1

Non-Patent Literature 2

Non-Patent Literature 3

Non-Patent Literature 4

Non-Patent Literature 5

Non-Patent Literature 6

Non-Patent Literature 7

Non-Patent Document 8

Non-Patent Document 9

Summary of the Invention

Problems to be Solved by the Invention

[0016] In order to examine the anti-inflammatory effect of a mixed crude drug extract of Longanae Arillus, Ligustici Tenuissimi Rhizoma, and Polygalae radix, the inventors conducted in vitro experiments such as inhibition tests on the expression of cytokines (RPLPO, TSLP, GM-CSF, and IL-1 beta) involved in skin inflammation (Experimental Example 1); in vivo experiments such as the atopic dermatitis inhibitory effect using BALB / C mice (Experimental Example 2); expression inhibition tests of various cytokines (GADPH, TSLP, GM-CSF, IL-4, IL-10, IL-13, IL-31, and IL-33) involved in skin inflammation using test animals (Experimental Example 3); and TSLP cytokine expression inhibition tests using test animals (Experimental Example 4). As a result of such investigations, the inventors finally completed the present invention by confirming that the mixed crude drug extract of the present invention strongly inhibits and improves the expression of the TLSP (thymic stromal lymphopoietin) cytokine and treats and improves skin inflammatory diseases.

Means for Solving the Problems

[0017] The technical solution for solving the problems of the background art lies in the development of a novel crude drug dosage form for treating and preventing skin inflammatory diseases.

[0018] Accordingly, an object of the present invention is to provide a topical pharmaceutical composition containing, as an active ingredient, a mixed herbal medicine extract of Longanae Arillus, Ligustici Tenuissimi Rhizoma, and Polygalae radix for suppressing TLSP (thymic stromal lymphopoietin) cytokine expression or treating and improving skin inflammatory diseases.

Effects of the Invention

[0019] As described above, the present inventors conducted in vitro experiments such as suppression tests on the expression of cytokines (RPLPO, TSLP, GM-CSF, and IL-1 beta) involved in skin inflammation (Experimental Example 1); in vivo experiments such as the atopic dermatitis suppression effect using BALB / C mice (Experimental Example 2); suppression tests on the expression of various cytokines (GADPH, TSLP, GM-CSF, IL-4, IL-10, IL-13, IL-31, and IL-33) involved in skin inflammation using test animals (Experimental Example 3); and a TSLP cytokine expression suppression test using test animals (Experimental Example 4). As a result, it was confirmed that the mixed composition of the present invention has a strong anti-inflammatory effect. Therefore, it was confirmed that the mixed extract of the present invention is very useful for improving or treating skin inflammation in the form of a topical pharmaceutical agent or a cosmetic composition.

Brief Description of the Drawings

[0020]

Figure 1

Figure 2

Modes for Carrying Out the Invention

[0021] The term "mixed crude drug extract" as defined in the present application refers to a mixed crude drug extract, that is, (a) a mixed crude drug extract of longan aril, ligusticum root, and ongi with a mixing ratio based on the dry weight (w / w) of 0.01 - 100:0.01 - 100:0.01 - 100 parts by weight (w / w), preferably 0.1 - 50:0.1 - 50:0.1 - 50 parts by weight (w / w), more preferably 0.1 - 10:0.1 - 10:0.1 - 10 parts by weight (w / w), still more preferably 1 - 5:1 - 5:1 - 5 parts by weight (w / w), and most preferably 1 - 3:1 - 3:1 - 3 parts by weight (w / w); or (b) a mixture of extracts of longan aril, ligusticum root, and ongi with a mixing ratio based on the dry weight (w / w) of 0.01 - 100:0.01 - 100:0.01 - 100 parts by weight (w / w), preferably 0.1 - 50:0.1 - 50:0.1 - 50 parts by weight (w / w), more preferably 0.1 - 10:0.1 - 10:0.1 - 10 parts by weight (w / w), still more preferably 1 - 5:1 - 5:1 - 5 parts by weight (w / w), and most preferably 1 - 3:1 - 3:1 - 3 parts by weight (w / w).

[0022] Another object of the present invention is to provide a TLSP expression inhibitor containing, as an active ingredient, a mixed crude drug extract of longan aril, ligusticum root, and ongi in an amount that suppresses the TLSP (thymic stromal lymphopoietin) cytokine.

[0023] The term "extract" disclosed in the present application includes an extract that can be extracted with one or more solvents selected from water, C 1 -C 4 lower alkyl alcohols such as methanol, ethanol, propanol, butanol, etc., acetone, ethyl acetate, chloroform, hexane, butylene glycol, propylene glycol, or glycerin, preferably water, methanol, ethanol, more preferably water or 10 - 90% (v / v) ethanol in water, and most preferably water or 20 - 80% (v / v) ethanol in water.

[0024] As used herein, the term "skin inflammatory disease" includes chronic recurrent dermatitis such as pruritus due to aging or atopy, atopic dermatitis, psoriasis; contact dermatitis, seborrheic dermatitis, neurodermatitis, xeroderma, erythema, inflammatory dermatitis, psoriasis or atopic disease; preferably, chronic recurrent dermatitis such as pruritus due to aging or atopy, atopic dermatitis, psoriasis due to increased expression of cytokines; contact dermatitis, seborrheic dermatitis, neurodermatitis, xeroderma, erythema, inflammatory dermatitis, psoriasis or atopic disease; more preferably, chronic recurrent dermatitis such as pruritus due to aging or atopy, atopic dermatitis, psoriasis due to increased expression of cellular TLSP cytokines; contact dermatitis, seborrheic dermatitis, neurodermatitis, xeroderma, erythema, inflammatory dermatitis, psoriasis or atopic disease, selected from the group of diseases. As used herein, the term "anti-inflammatory" is not limited thereto and means all mechanisms that suppress various inflammations.

[0025] Inflammation is part of a complex biological response of body tissues to harmful stimuli such as pathogens, damaged cells, or irritants, and the non-specific immune responses such as heat, pain, redness, and swelling are called the "inflammatory response".

[0026] Inflammation can be classified as: (a) acute inflammation, which is the body's initial response to harmful stimuli, achieved by increased movement of plasma and white blood cells (especially granulocytes) from the blood to the damaged tissue, followed by a series of biochemical events being propagated and the inflammatory response maturation associated with various cells in the local vascular system, immune system, and damaged tissue being achieved; and (b) inflammation known as chronic inflammation, which results in a progressive change in the types of cells present at the inflammation site, for example, monocytes, and is characterized by simultaneous destruction and healing of tissues during the inflammatory process.

[0027] Generally, macrophages of damaged cells release various cytokines, activate T lymphocytes, and fat cells, which are lymphocytes, release various histamines, causing an internal barrier reaction and inducing inflammation of infected cells. Therefore, the expression level of cell cytokines can be used as an indicator of the activation of the inflammatory response (other modes, such as anti-inflammatory activity). The "anti-inflammatory activity" disclosed in the present application means the inhibitory activity against various skin inflammations.

[0028] Cytokines mean various immunological substances including chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors produced by a wide range of cells including immune cells such as macrophages, B lymphocytes, T lymphocytes, and fat cells, endothelial cells, fibroblasts, and all substrate cells released through the immunological progression caused by the invasion of various pathogens, such as viruses.

[0029] Generally, cytokines are released in the early stage of infection, but when the immune system is abnormally activated, they are continuously released. When high levels of cytokines are released over a long period, such as more than one week, the inventors call this a "cytokine storm". This is a physiological reaction in which the innate immune system becomes unable to suppress pro-inflammatory signaling molecules called cytokines, causing excessive release, and immune cells home to the infection site in extremely large numbers, worsening inflammation, relaxing blood vessels and causing extravasation, and in the worst case, leading to death. The term "inhibitory activity of cytokine expression" disclosed in the present application can be interpreted as the prevention, treatment, or improvement of cytokine storm.

[0030] The term "cytokine" disclosed in the present application includes, but is not limited to, various cytokines involved in dermatitis such as atopic dermatitis, specifically, TLSP (thymic stromal lymphopoietin), colony-stimulating factors (CSF), such as GM-CSF (granulocyte-macrophage colony-stimulating factor), M-CSF (macrophage colony-stimulating factor), G-CSF (granulocyte colony-stimulating factor), interleukins, such as interleukin-1 (IL-1), IL-4, IL-10, IL-12, IL-13, IL-31, IL-33, etc., tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ), and cytokines selected from the group consisting of these.

[0031] The extract of the present invention can be prepared according to the following preferred embodiments.

[0032] In the case of the present invention, the extract can be prepared as follows.

[0033] The term "mixed crude drug extract of longan pulp, ligusticum root, and angelica" defined in the present application refers to the step of slicing and washing "longan pulp, ligusticum root, and angelica" and using them as the basic extract substance in the first step; the step of mixing well at a mixing ratio based on the dry weight (w / w) of longan pulp, ligusticum root, and angelica in the range of 0.01-100:0.01-100:0.01-100 parts by weight (w / w), preferably 0.1-50:0.1-50:0.1-50 parts by weight (w / w), more preferably 0.1-10:0.1-10:0.1-10 parts by weight (w / w), still more preferably 1-5:1-5:1-5 parts by weight (w / w), and most preferably 1-3:1-3:1-3 parts by weight (w / w) to obtain the mixture substance in the second step; in the third step, water, C 1 -C 4Lower alkyl alcohols, such as methanol, ethanol, propanol, butanol, etc., acetone, ethyl acetate, chloroform, hexane, butylene glycol, propylene glycol or glycerin, preferably water, methanol, ethanol, more preferably water or 10 - 90% (v / v) ethanol in water, most preferably water or 20 - 80% (v / v) ethanol in water, an extraction solvent selected from the group consisting of 1 - 20 volumes (v / w), preferably 4 - 8 volumes (v / w) is added to the mixture; In the fourth step, hot water extraction, cold water extraction, reflux extraction or ultrasonic extraction, preferably by hot water extraction, is carried out for 1 - 24 hours, preferably in the range of 2 - 12 hours, in a temperature range of 50 °C - 120 °C, preferably about 80 °C - 100 °C, to extract each solution; The extraction process is repeated, and each filtrate is collected through filtration, freeze-drying, natural drying or hot air drying, preferably by freeze-drying, to obtain the mixed crude drug extract of longan meat, ligusticum root and ongi of the present invention.

[0034] Another object of the present invention is to provide a method for preparing a mixed crude drug extract of longan meat, ligusticum root and ongi of the present invention as described above.

[0035] Another object of the present invention is to provide a topical pharmaceutical composition containing, as an active ingredient, a mixed crude drug extract of longan meat, ligusticum root and ongi prepared by the above method for suppressing TLSP (thymic stromal lymphopoietin) cytokine or treating and improving skin inflammatory diseases.

[0036] According to another aspect of the present invention, there is also provided a method for suppressing TLSP (thymic stromal lymphopoietin) cytokine in a mammal or treating or improving a skin inflammatory disease, which includes the step of topically administering an effective amount of a mixed crude drug extract of longan meat, ligusticum root and ongi and a pharmaceutically acceptable carrier thereof to a mammal.

[0037] According to another aspect of the present invention, there is also provided the use of the active ingredient of a mixed crude drug extract of longan pulp, ligusticum root, and atractylodes rhizome as a suppressant of mammalian TLSP (thymic matrix lymphopoietin) cytokine including humans, or for preparing a topical dosage form used for treating or improving skin inflammatory diseases.

[0038] The composition of the present invention can further contain conventional carriers, adjuvants, or diluents depending on the method of use. The carrier is preferably used as an appropriate substance depending on the use and the method of application, but is not limited thereto. Appropriate diluents are listed in the written text of Remington’s Pharmaceutical Science (Mack Publishing co, Easton PA).

[0039] The following dosage formulating methods and excipients are merely illustrative and do not limit the present invention in any way.

[0040] The composition of the present invention according to the present invention can be provided as a topical pharmaceutical composition containing pharmaceutically acceptable carriers, adjuvants, or diluents, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginic acid, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. The dosage form can further contain fillers, anticoagulants, lubricants, humectants, flavoring agents, emulsifying agents, preservatives, etc. The composition of the present invention can be formulated so as to provide rapid, sustained release, or delayed release of the active ingredient after administration to a patient via any procedure well known in the art.

[0041] For topical administration, the extract of the present invention can be formulated in the form of ointments and creams, including topical preparations such as creams, gels, patches, spray solutions, emulsions, ointments, lotions, liniments, balms, solutions, suspensions, packs, pastes, aerosols, cataplasms, etc.

[0042] The composition of the present invention in pharmaceutical dosage form can be used in the form of its pharmaceutically acceptable salts, can be used alone or in suitable combinations, and can also be used in combination with other pharmaceutically active compounds.

[0043] The preferred dosage of the extract or composition of the present invention varies depending on the condition and body weight of the subject, severity, drug form, route of administration and duration of administration, and can be selected by those skilled in the art. However, in order to obtain a preferred effect, it is generally recommended to topically administer the extract of the present invention in an amount in the range of 0.01 - 10 g / kg, preferably 1 - 5 g / kg (weight / day). The dosage can be administered as a single or multiple doses per day. From the perspective of the composition, the present extract should be present in an amount of 0.01 - 80% by weight, preferably 0.5 - 50% by weight based on the total weight of the composition.

[0044] The inventors have demonstrated that the anti-inflammatory effect of the present composition is strong by performing in vitro experiments such as suppression tests on the expression of cytokines (RPLPO, TSLP, GM-CSF and IL-1β) involved in skin inflammation (Experimental Example 1); in addition to in vitro experiments such as the effect of suppressing atopic dermatitis in BALB / C mice (Experimental Example 2); suppression tests on the expression of various cytokines (GADPH, TSLP, GM-CSF, IL-4, IL-10, IL-13, IL-31 and IL-33) involved in skin inflammation using test animals (Experimental Example 3); and TSLP cytokine expression suppression tests using test animals (Experimental Example 4). It was confirmed that the mixed extract of the present invention is very useful for improving or treating skin inflammatory diseases in the form of topical drugs or cosmetic compositions.

[0045] Another object of the present invention is to provide a cosmetic composition containing, as an active ingredient, a mixed herbal extract of longan pulp, ligusticum root, and atractylodes rhizome, which suppresses TLSP (thymic stromal lymphopoietin) cytokine or is effective in treating and improving skin inflammatory diseases in an effective amount.

[0046] The cosmetic composition of the present invention preferably contains 0.001 to 40% by weight, more preferably 0.01 to 10% by weight of the composition of the present invention based on the total weight of the composition. Other components may be a mixture of components of conventional cosmetic compositions well known in the art.

[0047] The cosmetic composition of the present invention preferably contains 0.001 to 40% by weight, more preferably 0.01 to 10% by weight of the composition of the present invention based on the total weight of the composition. Other components may be a mixture of components of conventional cosmetic compositions well known in the art.

[0048] The cosmetic dosage form containing the above composition can be prepared in any form such as, for example, lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, foundation, essence, nutritional essence, pack, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, treatment, beauty liquid, etc.

[0049] The following dosage form preparation methods and excipients are merely illustrative and do not limit the present invention in any way.

[0050] The cosmetic composition of the present invention can further contain an additive selected from the group consisting of water-soluble vitamins, fat-soluble vitamins, peptide polymers, polysaccharide polymers, sphingolipids, and seaweed extracts.

[0051] Preferred water-soluble vitamins are those that can be formulated in cosmetics, but various vitamins such as vitamin B 1 、B2 , B 6 , pyridoxine, pyridoxine HCl, vitamin B 12 , pantothenic acid, nicotinic acid, nicotinamide, folic acid, vitamin C, vitamin H, etc., their salts, for example, thiamine HCl salt, ascorbic acid Na salt, etc. or their derivatives, for example, ascorbic acid-2-phosphonic acid Na salt, ascorbic acid-2-phosphonic acid Mg salt are preferred, and these can be obtained by conventional methods such as microbial conversion method, purification method from microbial cultures, enzymatic method or chemical synthesis method.

[0052] Preferred fat-soluble vitamins can be formulated in cosmetics, but various vitamins including the fat-soluble vitamins used in the examples of the present invention, for example, vitamin A, D 2 , D 3 , E (dl-α-tocopherol, d-α-tocopherol, d-d-tocopherol), and their derivatives, for example, ascorbyl palmitate, ascorbyl stearate, ascorbyl dipalmitate, dl-α-tocopherol acetate, nicotinic acid dl-α-tocopherol vitamin E, dl-pantothenyl alcohol, D-pantothenyl alcohol, pantothenyl ethyl ether, etc. are preferred, and these can be obtained by conventional methods such as microbial conversion method, purification method from microbial cultures, enzymatic method or chemical synthesis method.

[0053] Preferred peptide polymers can be formulated in cosmetics, but collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed gelatin, keratin, etc. including the peptide polymers used in the examples of the present invention are preferred.

[0054] Preferred polysaccharide polymers can be formulated in cosmetics, but hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or their salts (such as Na salt) are preferred. For example, chondroitin sulfate or its salts can usually be purified from mammals or fish and used.

[0055] Preferred sphingolipids can be incorporated into cosmetics, and ceramides, phytosphingosine, sphingo-lipopolysaccharides, etc. are preferred. Sphingolipids can be obtained by purifying from mammals, fish, shellfish, yeast or plants by conventional methods.

[0056] Preferred seaweed extracts can be incorporated into cosmetics, and extracts of brown algae, red algae, green algae, etc. or purified carrageenan, alginic acid, sodium alginate, potassium alginate isolated from these are preferred. Algae extracts can be obtained by purifying from seaweed by conventional methods.

[0057] The cosmetic composition of the present invention can be combined with the above essential components, if necessary, with other components conventionally used in cosmetic compositions.

[0058] The other preferred components described above may include oil components, humectants, softeners, surfactants, organic or inorganic dyes, organic powders, ultraviolet absorbers, preservatives, antiseptics, antioxidants, plant extracts, pH adjusters, alcohols, pigments, perfumes, refrigerants, circulators, antihidrotics, distilled water, etc.

[0059] Preferred oil components may include ester oils, hydrocarbon oils, silicone oils, fluorine oils, animal oils, vegetable oils, etc.

[0060] The preferred ester oils described above are glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, isopropyl adipate, isoalkyl neopentanoate, glyceryl tri(caprylic, capric acid), trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di(caprylic, capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl tripalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldodecyl isostearate, polyglycerol oleanolate ester, polyglycerol isostearate ester, triisocetyl citrate, triisoalkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate,It may contain cetyl lactate, octyldecyl lactate, triethyl citrate, acetyltriethyl citrate, acetyltributyl citrate, trioctyl citrate, diisostearyl maleate, di(2-ethylhexyl) hydroxystearate, 2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoyl hydroxystearate, stearyl 12-stearoyl hydroxystearate, isostearyl 12-stearoyl hydroxystearate.

[0061] The preferred hydrocarbon oils described above may include squalene, liquid paraffin, α-olefin oligomers, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum, etc. The preferred silicone oils described above may include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane-methyl cetyloxysiloxane copolymer, dimethylsiloxane-methyl stearoxysiloxane copolymer, alkyl-modified silicone oil, amino-modified silicone oil, etc.

[0062] The preferred fluorine oils described above may include perfluoropolyether, etc.

[0063] Preferred animal or vegetable oils may include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, safflower oil, soybean oil, corn oil, rapeseed oil, amygdalin oil, palm kernel oil, palm oil, castor oil, sunflower oil, fruit oil, cottonseed oil, coconut palm oil, cucui nut oil, wheat embryo bud oil, rice germ oil, shea butter, evening primrose oil, macadamia nut oil, medo home oil, egg yolk oil, lanolin, hempseed oil, mink oil, orange ruppy oil, jojoba oil, candelilla wax, liquid lanolin, solid castor wax, etc.

[0064] Preferred humectants can include water-soluble low-molecular-weight humectants, lipophilic low-molecular-weight humectants, water-soluble polymers, and fat-soluble polymers.

[0065] Specifically, preferred water-soluble low-molecular-weight humectants may include serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol (degree of polymerization > 2), polypropylene glycol (degree of polymerization > 2), lactic acid, lactate, etc.

[0066] Preferred lipophilic low-molecular-weight humectants may include cholesterol, cholesteryl ester, etc.

[0067] Preferred water-soluble polymers may include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, HMC (hydroxymethylcellulose), HEC (hydroxyethylcellulose), HPC (hydroxypropylcellulose), carboxymethylcellulose, water-soluble chitin, chitosan, dextrin, etc.

[0068] Preferred fat-soluble polymers may include polyvinylpyrrolidone-eicosene copolymer, polyvinylpyrrolidone-hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, silicone polymer, and the like.

[0069] Preferred softeners may include cholesteryl long-chain acyl glutamate, cholesteryl hydroxystearate, 12-hydroxystearic acid, rogic acid, cholesteryl lanolin fatty acid ester, and the like.

[0070] Preferred surfactants may include nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, and the like.

[0071] Specifically, preferred nonionic surfactants may include self-emulsifying glycerin monostearate, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene (POE) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POE-POP copolymer, POE-POP alkyl ether, polyether-modified silicone, alkanolamide laurate, alkylamine oxide, hydrogenated soybean phospholipid, and the like.

[0072] Preferred anionic surfactants may include fatty acid soap, alpha-acylsulfonic acid, alkyl sulfonate, alkylaryl sulfonate, alkylnaphthalene sulfonate, alkyl sulfonate, POE alkyl ether sulfate, alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate, alkylroylalkyl taurine salt, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, alkyl sulfacetate, acylated hydrolyzable collagen peptide salt, perfluoroalkyl phosphate ester, and the like.

[0073] Preferred cationic surfactants may include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, lanolin derivative quaternary ammonium, etc.

[0074] Preferred amphoteric surfactants may include carboxybetaine type, amidobetaine type, hydroxysulfobetaine type, phosphobetaine type, aminocarboxylic acid, imidazoline derivative type, amidoamine type, etc.

[0075] Preferred organic and inorganic dyes include, as inorganic dyes, silicic acid, silica, magnesium silicate, talc, sericite, mica, kaolin, red iron oxide, clay, bentonite, titanium film mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, aluminum oxide, calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, ferrous oxide, chromium oxide, chromium hydroxide, calamine, carbon black and their composites; as organic dyes, polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluororesin, silicone resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, styrene co-divinylbenzene copolymer, silk powder, cellulose, CI Pigment Yellow, CI Pigment Orange; and their composites, etc.

[0076] Preferred organic powders include metal soaps such as calcium stearate; alkyl phosphonate metal salts such as sodium cetyl zinc phosphate, zinc laurate, calcium laurate; acyl amino acid polyvalent metal salts such as calcium N-lauroyl-β-alanine, zinc N-lauroyl-β-alanine, calcium N-lauroyl-glycine, etc.; amide sulfonic acid polyvalent metal salts such as calcium N-lauroyl-taurine, calcium N-palmitoyl-taurine; N-acyl basic amino acids such as Nε-lauroyl-L-lysine, Nε-palmitoyl-lysine, Nα-palmitoyl-ornithine, Nα-lauroylarginine, hardened lanolin fatty acid acylarginine, etc.; N-acyl polypeptides such as N-lauroylglycylglycine; α-amino fatty acids such as α-aminocaprylic acid, α-aminolauric acid, etc.; and may also include polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, styrene-divinylbenzene copolymer, tetrafluoroethylene, etc.

[0077] Preferred UV absorbers may include para - aminobenzoic acid, ethyl para - aminobenzoate, amyl para - aminobenzoate, octyl para - aminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, benzyl cinnamate, 2 - ethoxyethyl paramethoxycinnamate, octyl paramethoxycinnamate, diparamethoxycinnamic acid mono - 2 - ethylhexyl glycerol, isopropyl paramethoxycinnamate, diisopropyl - diisopropyl cinnamate ester mixture, urocanic acid, ethyl urocanic acid, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenone disulfonate (dihydroxy methoxy benzophenone disulfonate Na), dihydroxybenzophenone, tetrahydroxybenzophenone, 4 - tert - butyl - 4’ - methoxydibenzoylmethane, 2,4,6 - trianilino - p - (carbo - 2’ - ethylhexyl - 1’ - oxy) - 1,3,5 - triazine, 2 - (2 - hydroxy - 5 - methylphenyl) benzotriazole, etc.

[0078] Preferred preservatives may include hinokitiol, trichloric acid, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcinol, isopropylmethylphenol, azulene, salicylic acid, zinc pyrithione, benzalkonium HCl, photosensitizer 301, mononitroguaiacol Na, undecylenic acid, etc.

[0079] Preferred antioxidants may include butylhydroxyanisole, propyl gallate, erythorbate, etc.

[0080] Preferred pH adjusters may include citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium hydrogen phosphate, etc.

[0081] Preferred alcohols may include cetyl alcohol and the like.

[0082] In addition, other components that can be added to the above components and their amounts are not limited within the scope of the object and effect of the present invention, but the content of other components is preferably 0.01 - 5% of the total composition content, and more preferably in the range of 0.01 - 3%.

[0083] The cosmetic composition of the present invention can be transformed into solutions, emulsions, adhesive mixtures, and the like.

[0084] The above components such as water-soluble vitamins, fat-soluble vitamins, peptide polymers, polysaccharide polymers, sphingolipids, seaweed extracts, and additional components that can be added as necessary in addition to the above components can be obtained by conventional methods described in the literature (Matsumoto Mithio; Manual for the development of transdermal applied preparation. Seisi Press, 1st Ed., 1985).

[0085] Since the compound of the present invention has no toxicity and side effects, it can be used safely.

[0086] It will be apparent to those skilled in the art that various changes and modifications can be made to the compositions, uses, and formulations of the present invention without departing from the spirit or scope of the present invention.

[0087] The present invention will be more specifically described by the following examples. However, it should be understood that the present invention is not limited to these embodiments in any way.

Examples

[0088] The following examples and experimental examples are for further illustrating the present invention without limiting the scope of the present invention.

[0089] Example 1. Preparation of the mixed extract (1) of the present invention After cutting 20 g of dried longan aril (Longanae Arillus) (Buyoung Yakup Co., Ltd.), 20 g of dried ligusticum tenuissimum rhizome (Ligustici Tenuissimi Rhizoma) (Buyoung Yakup Co., Ltd.), and 20 g of dried polygala root (Polygalae radix) (Buyoung Yakup Co., Ltd.) into small pieces, they were mixed with 6 times the volume (v / w) of a 20% ethanol aqueous solution, and the mixture was refluxed and extracted at 90 ± 5 °C for 3 days. The extract was filtered through filter paper (pore size less than 10 μm) to remove the residue, and then the remaining residue was further extracted twice with 4 times the volume (v / w) of a 20% ethanol aqueous solution, and the extract was filtered through filter paper (pore size less than 10 μm).

[0090] The collected extracts were mixed together and concentrated under vacuum (16 - 21 Brix) to obtain a concentrated extract. The concentrated extract was dried by a freeze-drying process, pulverized (less than 50 mesh), and 20.5 g of the mixed extract (1) of the present invention (hereinafter referred to as "WIN-1001X") was obtained (dry basis powder, yield 33.4%).

[0091] Examples 2 - 6. Preparation of the mixed extracts (2) - (6) of the present invention All procedures were the same as in Example 1 except that different mixing ratios and different solvents were used from those disclosed in Example 1, and various mixed extracts of the present invention of longan aril (LA), ligusticum tenuissimum rhizome (LT), and polygala root (PR), that is, the mixed extract (2) to the mixed extract (6) of the present invention were obtained. These were used as test samples in the following experiments.

[0092]

Table 1

[0093] Experimental Example 1. Inhibitory effect on cytokine expression (in vitro) To determine the anti-inflammatory activity of the extract of the present invention, the following cytokine expression inhibition test using HaCaT cells was conducted according to the procedure described in the literature (Jeong et al., 2019, J. Invest. Dermatol., May; 139 (5): pp1098-1109).

[0094] HaCaT cells (human epidermal keratinocytes, 300493, CLS) were inoculated into DMEM medium containing 10% fetal bovine serum, 100 units / ml of penicillin, and 100 μg / ml of streptomycin (D6429, Sigma-Aldrich Co., Ltd), and incubated in an incubator (HERA cell 150i, Thermo Fisher Scientific Co., Ltd) while maintaining an optimal humidity (85-95%) and a 5% CO 2 atmosphere.

[0095] To perform the gene expression test, the incubated cells were transferred to 12 wells, treated with 50 ng / ml of TNF alpha (RC214-12, Biobasic Co., Ltd) for 1 hour together to induce an inflammatory response. Dexamethasone (200 nM, positive control group, "DEX", D4902, Sigma-Aldrich Co., Ltd.) and distilled water (negative control group, "DIW") were used as comparative control groups.

[0096] One hour after inducing inflammation, 1 μg / ml of the extract of the present invention prepared in the examples was treated in the same medium and incubated for 1 hour. After incubation, RNA (FATRR-001, Favorgen) was extracted from the cells, and cDNA was synthesized from the RNA using a cDNA synthesis kit (RRO36A, TAKARA). After performing a polymerization reaction using the synthesized cDNA and a Sybrgreen kit (RT500M, Enzynomics), real-time PCR was performed using primers (RPLPO, TSLP, GM-CSF, and IL-1β) for various cytokines involved in skin inflammation as shown in Table 2.

[0097] [Table 2]

[0098] As can be seen from Table 3 showing the quantitative results of RT-PCR, in the test sample group treated with the extract of the present invention, the expression levels of various cytokines involved in skin inflammation were significantly suppressed compared to the negative control group treated with distilled water (DIW), and it was confirmed that the inhibitory activity of the test sample on the expression of various cytokines involved in skin inflammation was equivalent to that of the positive control group treated with dexamethasone (DEX).

[0099] Therefore, it was confirmed that the various mixed extracts of the present invention prepared in Examples 1 to 6 have a strong inhibitory effect on skin inflammation.

[0100]

Table 3

[0101] Experimental Example 2. Atopic dermatitis inhibitory effect (in vitro) To confirm the atopic dermatitis inhibitory effect of the extract of the present invention, an animal model test using mice was conducted according to the method described in the reference (Li et al., Drug Des Devel Ther., 2016, Feb. 19; 10: 781-191).

[0102] 100 μl of 0.15% (w / v) DNFB (2,4-dinitrofluorobenzene, D1529, Sigma-Aldrich Co., Ltd.) was applied to the abdominal cavity of 6-week-old female BALB / C mice (DBL Co., Ltd., Incheon, Korea). After removing the hair on the central back, it was applied at 3-day intervals from day 7 to day 16 to induce skin inflammation. Not only the test sample (the extract WIN-1001X of the present invention, prepared in the example, 10 mg / ml), but also dexamethasone (200 μM, positive control group, "DEX", D4902, Sigma-Aldrich Co., Ltd.) and distilled water (negative control group, "DIW") used as comparative controls were applied in total from day 7, the first treatment day of DNFB, to day 16.

[0103] For comparison with the test group, a similar test was conducted except that acetone was used instead of DNFB and DIW was used instead of the test sample according to the above procedure.

[0104] As shown in Fig. 1, it was found that dermatitis occurred on the skin of the back of the mice on day 16 after sample treatment. The severity of dermatitis was based on four symptoms, namely (i) erythema / bleeding, (ii) edema, (iii) abrasion / maceration, and (iv) scar / dryness, with a total of 12 points, and was classified into four grades, namely 0 points (asymptomatic), 1 point (simple dermatitis), 2 points (moderate dermatitis), and 4 points (severe dermatitis).

[0105] As shown in Fig. 1 and Table 4, it was confirmed that the mixed extract of the present invention showed a strong improvement effect on dermatitis compared to the negative control group, and its effect was similar to that of the positive control group treated with dexamethasone (DEX).

[0106]

Table 4

[0107] In addition, histological analysis of the skin tissue of the test animals was performed.

[0108] Specifically, the skin tissue of the back where dermatitis occurred was fixed in a 4% (w / v) paraformaldehyde solution (P6148, Sigma-Aldrich) in a shaker (CR300, FINEPCR) maintained at 4°C on the 16th day after sample treatment and 12 hours after fixation, dehydrated, the cleared tissue was embedded in paraffin, and sliced (5 μm width) to prepare tissue sections.

[0109] The tissue sections were stained with H&E stain {hematoxylin (S3309 <DAKO) & eosin (109844, Millipore)} for staining the skin epidermal layer or toluidine blue (TB, 185426, Sigma-Aldrich) for staining the mast cells infiltrated in the inflammatory lesions, and the results were observed using a microscope (EVOS XL., Life Technologies).

[0110] As can be seen from Figure 2 and Tables 5 - 6, in the test group treated with the mixed extract of the present invention, the width of the skin epidermal layer was significantly reduced compared to the negative control group treated with DIW, and the number of mast cells infiltrated in the inflammatory lesions decreased. The effect was confirmed to be similar to that of the positive control group treated with dexamethasone (DEX).

[0111]

Table 5

[0112]

Table 6

[0113] Experimental Example 3. Cytokine Expression Inhibitory Effect (in vivo) To confirm the anti-inflammatory activity of the extract of the present invention, the following cytokine expression inhibition test was performed using test animals according to the procedure described in the literature (Li et al., Drug.Des.Devel.Ther., 2016, Feb 19;10:781 - 191).

[0114] On the 16th day after DNFB treatment, RNA (FATRR-001, Favorgan) was extracted from the skin on the back of the mice prepared in Experimental Example 2, and cDNA was synthesized from the RNA using a cDNA synthesis kit (RRO36A, TAKARA). After performing a polymerization reaction using the synthesized cDNA and a Sybrgreen kit (RT500M, Enzynomics), real-time PCR was performed using primers for various cytokines (GADPH, TSLP, GM-CSF, IL-4, IL-10, IL-13, IL-31, and IL-33) involved in skin inflammation as shown in Table 7.

[0115]

Table 7

[0116] As can be seen from Table 8 showing the quantitative results of RT-PCR, the test sample group treated with the extract of the present invention significantly suppressed the expression levels of various cytokines involved in skin inflammation compared to the negative control group treated with distilled water (DIW), and it was confirmed that the inhibitory activity of the test sample on the expression of various cytokines involved in skin inflammation was equivalent to that of the positive control group treated with dexamethasone (DEX).

[0117] Therefore, it was confirmed that the mixed extract of the present invention prepared in the examples has a strong inhibitory effect on skin inflammation.

[0118]

Table 8

[0119] Experimental Example 4. TSLP Cytokine Expression Inhibitory Effect (in vivo) To confirm the anti-inflammatory activity of the extract of the present invention, the following TSLP cytokine expression inhibitory test using test animals was performed according to the procedure described in the literature (Li et al., Drug Des Devel Ther., 2016, Feb 19;10:781-191).

[0120] On the 16th day after DNFB treatment, RNA (FATRR-001, Favorgan) was extracted from the skin on the back of the mice prepared in Experimental Example 2, and cDNA was synthesized from the RNA using a cDNA synthesis kit (RRO36A, TAKARA). After performing a polymerization reaction using the synthesized cDNA and a Sybrgreen kit (RT500M, Enzynomics), real-time PCR was performed using primers for the TSLP cytokine involved in skin inflammation as shown in Table 7.

[0121] As can be seen from Table 9 showing the quantitative results of RT-PCR, the test sample group treated with the extract of the present invention significantly suppressed the expression level of the TSLP cytokine involved in skin inflammation compared to the negative control group treated with distilled water (DIW), and it was confirmed that the inhibitory activity of the test sample on the expression of the TSLP cytokine involved in skin inflammation was equivalent to that of the positive control group treated with dexamethasone (DEX).

[0122] Therefore, it was confirmed that the mixed extract of the present invention prepared in the examples has a strong inhibitory effect on the expression of the TSLP cytokine.

[0123]

Table 9

[0124] Statistical analysis The mean and standard error were calculated from the test results obtained in the experiment. The significance test was analyzed using a t-test, and the significance level (P-value) was represented as P≤0.05=*, P≤0.01=**, and P≤0.001=***.

[0125] The method of the present invention Hereinafter, the formulation methods and types of excipients will be described, but the present invention is not limited thereto. Representative preparation examples will be described as follows.

[0126] Preparation of lotion 1.00% of the extract of the example (WIN-1001X) Glycerol 3.00% Ethanol 1.00% Propylene Glycol 0.10% Fragrance Trace amount Distilled water 100% or less

[0127] The skin preparation was prepared by dissolving the active ingredients according to the conventional lotion preparation method.

[0128] Preparation of emulsion Extract of Example (WIN-1002X) 3.00% L-Ascorbic Acid-2-Phosphate Magnesium 1.00% Soluble Collagen (1% solution) 1.00% Sodium Citrate 0.10% 1,3-Butylene Glycol 3.00% Distilled water 100% or less

[0129] The lotion preparation was prepared by dissolving the active ingredients according to the conventional lotion preparation method.

[0130] Preparation of cream Extract of Example (WIN-1003X) 3.00% Polyethylene Glycol Monostearate 2.00% Glycerol Monostearate 1.00% Cetyl Alcohol 4.00% Squalene 6.00% Tri-2-Glyceryl Ethylhexanoate 6.00% Sphingo-Glycolipid 1.00% 1,3-Butylene Glycol 3.00% Distilled water 100% or less

[0131] The cream preparation was prepared by dissolving the active ingredients according to the conventional cream preparation method.

[0132] Preparation of pack Extract of Example (WIN-1004X) 5.00% Polyvinyl alcohol 13.00% L-Ascorbic acid-2-phosphate magnesium 1.00% Lauroyl hydroxyproline 1.00% Soluble collagen (1% solution) 2.00% 1,3-Butylene glycol 3.00% Ethanol 5.00% Distilled water 100% or less Sugar 20 g Fructose 20 g Lemon flavor Optimal amount Distilled water 100 ml

[0133] The pack preparation was prepared by dissolving the active ingredient according to the conventional pack preparation method.

[0134] Preparation of essence Extract of Example (WIN-1005X) 2.00% Hydroxyethyl cellulose (2% solution) 12.00% Xanthan gum (2% solution) 2.00% 1,3-Butylene glycol 3.00% Glycerin concentration 4.00% Sodium hyaluronate 5.00% Distilled water 100 ml

[0135] The formulation of the lotion was prepared by dissolving the active ingredient according to the conventional lotion preparation method.

[0136] Therefore, it is clear that the present invention as described can be modified in various ways. Such modifications should not be regarded as departing from the spirit and scope of the present invention, and all such modifications that would be obvious to those skilled in the art are intended to be included within the following claims.

[0137] Having thus described the present invention, it is obvious that the same can be modified in various ways. Such modifications should not be regarded as departing from the spirit and scope of the present invention, and all such modifications as would be obvious to a person skilled in the art are intended to be included within the scope of the following claims.

Industrial Applicability

[0138] As described in the present invention, the present invention provides a topical composition and a cosmetic composition containing a mixed crude drug extract of longan aril, ligusticum root, and ongi. The inventors have shown that the anti-inflammatory effect of the mixed composition of the present invention is demonstrated by in vitro experiments such as suppression tests on the expression of cytokines (RPLPO, TSLP, GM-CSF, and IL-1β) involved in skin inflammation (Experimental Example 1); not only in vitro experiments, but also in vivo experiments such as the effect of suppressing atopic dermatitis in BALB / C mice (Experimental Example 2); suppression tests on the expression of various cytokines (GADPH, TSLP, GM-CSF, IL-4, IL-10, IL-13, IL-31, and IL-33) involved in skin inflammation using test animals (Experimental Example 3); and a suppression test on the expression of the TSLP cytokine using test animals (Experimental Example 4). Therefore, it was confirmed that the mixed extract of the present invention is very useful for improving or treating skin inflammation in the form of a topical pharmaceutical or cosmetic composition.

Claims

A method for manufacturing a topical pharmaceutical composition for treating or improving a skin inflammatory disease, comprising a mixed crude drug extract as an active ingredient for suppressing the expression of TSLP (thymic stromal lymphopoietin) cytokine, said manufacturing method comprising: Obtaining an extract of Longanae Arillus, an extract of Ligustici Tenuissimi Rhizoma, and an extract of Polygalae Radix; Mixing the extract of Longanae Arillus, the extract of Ligustici Tenuissimi Rhizoma, and the extract of Polygalae Radix to produce the mixed crude drug extract; The extract is extracted with one or more solvents selected from water, methanol, ethanol, propanol, butanol, acetone, ethyl acetate, chloroform, hexane, butylene glycol, propylene glycol, or glycerin. A method for manufacturing a topical pharmaceutical composition for treating or improving a skin inflammatory disease.

2. The method for manufacturing a topical pharmaceutical composition according to claim 1, characterized in that the mixed crude drug extract is a mixture of extracts of Longanae Arillus, Ligustici Tenuissimi Rhizoma, and Polygalae Radix having a mixing ratio based on the dry weights (w / w) of Longanae Arillus, Ligustici Tenuissimi Rhizoma, and Polygalae Radix in the range of 0.01 - 100:0.01 - 100:0.01 - 100 parts by weight (w / w).

3. The method for manufacturing a topical pharmaceutical composition according to claim 1, characterized in that the skin inflammatory disease is a disease selected from the group consisting of chronic relapsing dermatitis caused by aging or atopy; contact dermatitis, seborrheic dermatitis, neurodermatitis, xeroderma, erythema, inflammatory dermatitis, psoriasis, or atopic diseases.

4. Use of a mixed crude drug extract of Longanae Arillus, Ligustici Tenuissimi Rhizoma, and Polygalae Radix as an active ingredient for preparing a topical preparation used for suppressing TSLP (thymic stromal lymphopoietin) cytokine or treating or improving a skin inflammatory disease in mammals including humans.

5. A TSLP expression inhibitor comprising a mixed crude drug extract of Longanae Arillus, Ligustici Tenuissimi Rhizoma, and Polygalae Radix as an active ingredient in an amount that suppresses TSLP (thymic stromal lymphopoietin) cytokine. A method for manufacturing a cosmetic composition for improving a skin inflammatory disease, comprising a mixed crude drug extract as an active ingredient for suppressing the expression of TSLP (thymic stromal lymphopoietin) cytokine, said manufacturing method comprising: The step of obtaining longan arillus extract, rhizoma ligustici tenuissimi extract, and radix polygalae extract; The step of mixing the longan arillus extract, rhizoma ligustici tenuissimi extract, and radix polygalae extract to produce the mixed crude drug extract; The method for producing a cosmetic composition for improving skin inflammatory diseases, comprising: The extract is extracted with one or more solvents selected from water, methanol, ethanol, propanol, butanol, acetone, ethyl acetate, chloroform, hexane, butylene glycol, propylene glycol, or glycerin. A method for producing a cosmetic composition for improving skin inflammatory diseases.

7. The skin inflammatory disease is a chronic relapsing dermatitis caused by aging or atopy; a disease selected from the group of contact dermatitis, seborrheic dermatitis, neurodermatitis, xeroderma, erythema, inflammatory dermatitis, psoriasis, or atopic diseases. The method for producing a cosmetic composition according to claim 6, characterized in that.

8. The composition is in a form selected from lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, foundation, essence, nutritional essence, pack, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, treatment, beauty liquid. The method for producing a cosmetic composition according to claim 6, characterized in that.

Images