KR20150033797A - Pharmaceutical composition for prevention and treatment of atopic skin disease - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing and treating atopic dermatitis including a mixture extract of Heartleaf Houttuynia, Japanese Elm, Asiatic Pennywort and Glycyrrhiza uralensis Fischer as active ingredients wherein the mixture extract of Heartleaf Houttuynia, Japanese Elm, Asiatic Pennywort and Glycyrrhiza uralensis Fischer has effects of inhibiting atopic inflammation reaction on the whole human body and on parts of the human body, and inflammatory cytokine. In the present invention, the pharmaceutical composition incudes the mixture extract as an active ingredient and is accordingly used for preventing and treating atopic dermatitis.

Description

[0001] PHARMACEUTICAL COMPOSITION FOR PREPARATION AND TREATMENT OF ATOPIC SKIN DISEASE [0002]

The present invention relates to a pharmaceutical composition for the prevention and treatment of atopic skin diseases, and more particularly to a pharmaceutical composition for prevention and treatment of atopic skin diseases, which comprises a mixed extract of a herbal composition, ≪ / RTI >

Atopy is a Latin word for atopia. It is a word with an odd meaning. It is a constitution that is prone to cause a sensitive reaction. Atopy causes a series of allergic symptoms in the skin and respiratory mucosa of the person having the atopy inducing factor, the mucous membrane and the intestinal mucosa. People with atopy inducers often show hives in skin tests for protein substances that are frequently exposed to external environments such as house dust mites, ticks, animal hair, food, pollen, mold, etc. When eating or inhaling certain protein substances, Itching, skin seizures, urticaria, angioedema, sneezing, runny nose, nasal congestion, conjunctival hyperemia, and tears. Atopy inducing factors that cause these symptoms are inherited and appear familial. Allergic skin diseases caused by atopy inducers include atopic dermatitis, allergic rhinitis, asthma, allergic conjunctivitis, allergic intestinal inflammation, and atopic allergies. These diseases are caused by genetic predisposition, They can appear either singly or in combination. Among them, atopic dermatitis is a typical allergic skin disease that occurs in people with atopic allergy.

Blood tests and skin biopsy findings of atopic dermatitis patients showed that IgE and mononuclear leukocyte IgE receptor I expression and proliferation were increased in most of the blood. Increased IgE receptor expressing antigen transporter cells, activated T cells, IL-5, IL-10, IL-13 and eosinophils. In patients with atopic dermatitis, immunological abnormalities such as increased immediate hypersensitivity to environmental antigens, increased IgE and IgE receptor expression, increased antigen-specific T cells and Th2 cells, and when the disease is chronic, Th1 cells Lt; RTI ID = 0.0 > increased < / RTI > In addition, epidermal Langerhans cells and memory T cells are activated, dendritic cells, eosinophils, and mast cells are activated.

Atopic dermatitis often starts with infantile eczema, called infantile eczema. In the acute phase, the skin is itchy, red, swollen, or bloomed, blisters are caught, Scars such as hardened, thickened, streaked, or scales like rice flour are seen, or they are darkened or discolored.

In view of the pathogenesis, mechanism, and symptoms of atopic dermatitis known to date, the development of therapeutic agents for the skin diseases has been actively promoted. As a result, natural or synthetic immunosuppressants, steroids, and antihistamines have been developed .

However, steroid drugs used as therapeutic agents for atopic dermatitis have side effects such as hair growth, skin atrophy, skin pigment reduction, bacterial infection, acne formation, skin thinning, In severe cases, systemic symptoms due to hormones may appear, and when the use of the skin disease therapeutic agent is discontinued, symptoms may be rapidly intensified and the use of the therapeutic agent can not be stopped. Also, in most cases, the onset of atopic dermatitis occurs in infants before 5 years of age, so systemic administration of adrenocortical is not recommended. Therefore, steroid ointments with very low levels of hormones should be used only when needed for short periods of time.

In addition, the antihistamine agent used as a therapeutic agent for atopic dermatitis is used as a temporary measure to prevent the histamine from being liberated in the mast cell, thereby alleviating the itch symptoms. However, there may be side effects such as insomnia, loss of appetite, . In view of the characteristics of atopy, it is essential that the atopic dermatitis relieving agent and the therapeutic agent inhibit the systemic allergic reaction, particularly the inhibition of inflammatory cytokine expression.

On the other hand, Hwasungcho is a perennial herbaceous plant belonging to Saururus chinensis in plant classification, and the scientific name is Houttuynia Cordata . The natural product has an antibacterial action, and has effects such as anti-inflammation, analgesic and tissue regeneration. The Encyclopedia of Korea is made up of an eggplant and has ten kinds of medicinal effects, so it is said to be boiled in order to boil it after taking ten kinds of Chinese medicine, Chinese medicine, and childhood. It has been called as an abalone, etc. It has about 30 kinds of tinnitus. do. It is widely distributed in the Himalayas, China, Japan, Korea and East Asia to the Eurasia. In Korea, it is grown wild in Jeju Island, Ulleungdo, Anmyeondo and other farms. It grows well under the restoration of the lowlands or on the wet ground of the roadside, and the subterranean road spreads out long and the terrestrial is upright and grows about 20 ~ 50 cm in height. The whole is characterized by a characteristic smell when it is wound on the other side of the stomach. Two of these volatile components, undecanone and decanoly acetaldehyde, are believed to play an important role in the unique fishy of fish. As the efficacy of Hwasungcho, it is called 'a bleaching agent' in the oriental medicine 'to prevent blood and poison. It is used for the treatment of bleeding, decolonization, species, paralysis, pneumonia, eczema, eczema, otitis media and hypertension. It has strong antibacterial effect. In fact, it is known that the antiviral action against katharrh and influenza A type is excellent, and also the diuretic action, the action of arteriosclerosis, the prevention of hypertension and the strengthening action of capillary blood vessel are excellent.

Ulmus davidiana var. Japonica is a deciduous broad-leaved arboreous tree with dicotyledonous plant, nettle tree and elm. It is distributed in Korea, Japan, Sakhalin, Kuril Islands, northern China and eastern Siberia. m and a diameter of 60 cm. There are many kinds of elm, but the shape of leaves and the use of medicine are all the same. These elm have long been used as diuretics, remedies, or boils. The elm bark contains flavonoids, saponins (hemolysis index 1: 1900), tannins (3%), or a large amount of mucolytic components. These elm roots have been reported to act to strengthen the movement of the small intestine and bladder smooth muscle, to stop the salivation, to converge and to exert anti-inflammatory action. In addition, it is reported that when eating the essence of elm root skin or applying it to the skin, it quickly penetrates, it treats various skin diseases, and is effective in making skin beautiful and smooth. Also, elm root bark has been reported to have excellent effects on gastric ulcer, duodenal ulcer, small intestine ulcer, and colonic ulcer. On the other hand, elm leaves act as natural sleeping agents without side effects, and elm berries have antiparasitic and antibacterial functions.

Centella asiatica is a perennial plant belonging to the perennial plant. Its origin originates from the island of Madagascar in the eastern part of Africa and has started spreading and is widely distributed in India, Sri Lanka, Bengal and Himalayas It has been widely used for medicines such as wound healing in China and India. Asiatic acid, Asiatocoside, and Madecassic acid are the main components of the centrum, and they are effective in preventing skin troubles and aging. Many research reports have been made that have efficacy.

Licorice (Glycyrrhiza uralensis Fischer) is a perennial herb belonging to leguminosae and its scientific name is Glycyrrhiza uralensis Fisch. It contains glycyrrhizin, a sweet component, and is used as a sweetener. It has a therapeutic effect against various diseases, antibacterial action and excellent antioxidant ability. It is known to act on the heart, lungs, and gastric glands. It is known to be effective against ejang, wet, and livestock. It is used as an antidote to poisoning, and is used as an antipyretic agent and emollient. In addition, pain relief, weight gain, leukocyte increase, diuretic action, and anti-inflammatory action are known to be caused by sudden tense muscle or tissue (antimicrobial and antioxidant ability of water extract of licorice and spice, , ≪ / RTI > 793-799, 2007).

In the past, it has been reported that the extract of Hwasungcho extract or the mixed extract of Hwasungcho and other plants is effective for atopic skin disease. However, the mixed extract of Hwasungcho, Elm, Kwangpul and Licorice is excellent for allergic skin diseases including atopic dermatitis The effect has not been reported yet.

Accordingly, the present inventors have found that the composition containing the extract of Allium cepa, Elm tree, Centella asiatica and Licorice extract is superior to that of the extract alone in systemic inflammation, atopic inflammation and inflammatory diseases found in patients with atopic dermatitis Cytokine expression and the like can be generally and effectively improved and the present invention has been completed.

The present invention provides a pharmaceutical composition for preventing and treating atopic skin diseases, which comprises an extract of Rhodiola, Elmwood, Centella asiatica and licorice as an active ingredient.

The present invention also provides a cosmetic composition for preventing and treating atopic skin diseases containing the above-mentioned mixed extract as an active ingredient.

The objects of the present invention are not limited to the above-mentioned objects, and other objects and advantages of the present invention which are not mentioned can be understood by the following description, and will be more clearly understood by the embodiments of the present invention. It will also be readily apparent that the objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.

In order to achieve the above object, the present invention provides a pharmaceutical composition or a cosmetic composition for preventing and treating an allergic skin disease, which comprises, as an active ingredient, a mixed extract of Rhizobia seedlings, .

According to the present invention, the mixed extracts of Hwasungsu, Kinsho, elm and licorice have little toxicity and show the effect of preventing and treating atopic skin diseases caused by anti-inflammatory and antiallergic effects. It has an excellent effect for inhibiting the atopic inflammatory reaction, the systemic atopic inflammatory reaction, the local inflammatory reaction and the expression of the inflammatory cytokine, and thus has an excellent effect on allergic skin diseases including atopic dermatitis. Therefore, A pharmaceutical composition containing the compound can be usefully used for preventing and treating atopic skin diseases.

FIG. 1 is a graph showing the results of a comparison between an Evans standard curve (a: control group, b: comparative preparation example 1, c: comparative preparation example 2, d: comparative preparation example 3, e : Comparative Production Example 4, f: Production Example 1, g: Production Example 2, h: Production Example 3, i: Production Example 4, j: Production Example 5).
FIG. 2 is a table showing the mortality rate obtained by measuring the systemic allergic reaction inhibitory effect of the embodiment of the present invention. FIG.
FIG. 3 is a graph (a: control group, b: comparative preparation example 1, c: comparative preparation example 2, d: comparative preparation example 3, e: Comparative Production Example 4, f: Production Example 1, g: Production Example 2, h: Production Example 3, i: Production Example 4, j: Production Example 5).
FIG. 4 is a graph (a: positive control, b: negative control, c: comparative preparation example 1, d: comparative preparation example 2) showing the inhibitory effect on IL-6 among the inflammatory cytokines according to one embodiment of the present invention, f: Comparative Production Example 4, g: Production Example 1, h: Production Example 2, i: Production Example 3, j: Production Example 4, k: Production Example 5).
FIG. 5 is a graph (a: positive control, b: negative control, c: comparative preparation example 1, d: comparative preparation example 2) showing IL-8 inhibitory effect among inflammatory cytokines according to one embodiment of the present invention, f: Comparative Production Example 4, g: Production Example 1, h: Production Example 2, i: Production Example 3, j: Production Example 4, k: Production Example 5).
FIG. 6 is a graph (a: positive control, b: negative control, c: Comparative Preparation Example 1, d: Comparative Preparation Example 2, f: Comparative Production Example 4, g: Production Example 1, h: Production Example 2, i: Production Example 3, j: Production Example 4, k: Production Example 5).

BRIEF DESCRIPTION OF THE DRAWINGS The above and other objects, features and advantages of the present invention will become more apparent from the following detailed description of the present invention when taken in conjunction with the accompanying drawings, It can be easily carried out. In the following description, well-known functions or constructions are not described in detail since they would obscure the invention in unnecessary detail. Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

The present invention provides a pharmaceutical composition for the prevention and treatment of atopic skin diseases, which comprises an extract of Rhodophyta, Centella asiatica, Elm tree and licorice as an active ingredient.

In the composition according to the present invention, it is preferable to use the leaves, stems, roots, or extracts obtained by mixing two or more of them from each other. Of these, each leaf or leaf and stem extract is more preferable.

In the composition according to the present invention, the elm and licorice extract are preferably obtained by extracting each leaf, stem, root or a mixture of two or more thereof. Of these, the extracts of shells of stem or stem and roots of elm are more preferable.

In the composition according to the present invention, the extracts of Hwasungcho, Kunchuk extract, elm seedlings and licorice extract of the mixed extracts are 10-80 wt.% Based on in vitro and in vivo experiments, About 5 to 65% by weight of Bombyx mori, 5 to 65% by weight of elm, and 5 to 65% by weight of licorice. Furthermore, it is more preferable that 10 to 50% by weight of Rhododendron, 10 to 40% by weight of elm, 10 to 40% by weight of Lycoris spp., And 5 to 30% by weight of licorice. When the composition is out of the above range, there is no significant difference in the effect of suppressing the atopic reaction or the inflammatory reaction, as compared with the case where each extract is used alone.

The extracts of Bacillus thuringiensis, Centella asiatica, Elm trees and licorice extracts according to the present invention may be those extracted or commercially available according to methods well known in the art. Also, it can be used without restrictions such as cultivated or marketed, and it is cleaned and used. Dried herringbone, Centella asiatica, Elm trees and licorice are crushed to the appropriate size, placed in an extraction container and put in an appropriate amount of distilled water, alcohol or organic solvent. It is extracted at a suitable temperature for 24 hours or more, and then filtered with a filter paper to obtain a hot-water extract, an alcohol extract or an organic solvent extract according to the present invention.

As the hot-water extract, distilled water is preferably used as an extraction solvent, and it is more preferable to use tertiary distilled water. In the case of hot water extraction, it is preferable to heat the mixture at a temperature of 65 to 80 ° C for 24 hours.

The alcohol extract is preferably an alcohol of C ₁ -C ₄ as an extraction solvent, more preferably methanol, ethanol or a mixed solvent thereof. The organic solvent extract may be ethyl ether, chloroform, ethyl acetate, or a mixed solvent thereof. The organic solvent extract may be extracted by hot water heating in the same manner as in the hot water extract.

Furthermore, in the composition according to the present invention, it is preferable that the mixed extract is sterilized by irradiation with radiation.

Since the extract prepared by the above method is a natural ingredient, it can be safely used for the prevention and treatment of atopic skin diseases because there is no irritation to the human body.

The pharmaceutical composition according to the present invention containing the above-mentioned mixed extract can be effectively used for the prevention and treatment of allergic skin diseases such as atopic dermatitis, psoriasis, contact allergic dermatitis and urticaria.

When the skin is exposed to allergens, antigen-specific IgE binds to IgE receptors on the surface of Langerhans cells and is transferred to T cells on the surface of the antigen to activate T cells. In this case, Th2 is activated in allergic skin diseases, especially atopic dermatitis, and cytokines such as IL-4, IL-5, IL-6, IL-8, IL- As a result, the production of IgE is promoted in B cells and inflammatory cytokine and histamine are liberated by promoting degranulation of activated mast cells.

The above extracts were individually applied to the compositions of the present invention to determine the inhibitory effect on the inflammatory cytokines IL-6 and IL-8 of the mixed extract of Rhizobia, It can be seen that the present invention exhibits a very excellent inhibitory effect when measured by the use of these mixed extracts. In particular, it can be seen that such an inhibitory effect greatly depends on the mixing ratio of these extracts.

In addition, the present invention relates to a method for promoting adhesion of leukocytes to vascular endothelial cells in an inflammatory reaction using an eczema, an elm, an alfalfa, and a licorice as an active ingredient of the composition according to the present invention, increasing the microbial apoptotic ability of inflammatory cells, When the extracts were individually applied and measured from an experiment in which TNF-a, which acts on mononuclear phagocytes to produce cytokines involved in various inflammatory reactions, The results indicate that TNF-a inhibitory effect is remarkably improved when the mixed extract of the present invention is applied. These inhibitory effects are dependent on the mixing ratio of the above-mentioned mixed extracts as in the cases of IL-6 and IL-8 described above.

In addition, from the results of examining whether or not suppressing the local skin inflammation reaction and inhibiting the systemic allergic reaction, the compounds of the present invention, which are included as active ingredients, (20%) compared to the positive control (100%) (see Example 2 and Fig. 2). In addition, the vascular permeability is significantly reduced and the mortality of the systemic anaphylactic shock reaction is significantly reduced compared to the positive control (100%). Accordingly, the pharmaceutical composition according to the present invention can be effectively used for preventing and treating atopic skin diseases.

The pharmaceutical composition of the present invention having the preventive and therapeutic effect of an atopic skin disease may further comprise at least one pharmaceutically acceptable carrier, adipate or diluent By conventional methods.

The term "pharmaceutically acceptable" as used herein refers to a composition that is physiologically acceptable and does not normally cause an allergic reaction such as a gastrointestinal disorder, dizziness, or the like when administered to a human. In addition, the pharmaceutical composition of the present invention formulated as described above may be administered for the purpose of preventing or treating an atopic skin disease through a suitable administration route. Suitable routes of administration may include various routes including oral, transdermal, subcutaneous, intravenous, or muscular.

The pharmaceutical composition of the present invention can be formulated into oral or parenteral dosage forms according to the selected route of administration. In the case of formulation, the filler, the weight agent, the binder, the wetting agent, the disintegrant, the surfactant Of a diluent or excipient. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, such as starch, calcium carbonate, sucrose, Sucrose), lactose, gelatin, and the like.

In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As the non-aqueous agent and suspension agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. Witepsol, macrogol, Tween 61, cacao paper, laurin, glycerogelatin and the like may be used as a base for suppositories.

It is preferable that the mixed extract of Rhododendron, Elm, Kindergarten and Licorice according to the present invention is contained in an amount of 0.1 to 50% by weight based on the total weight of the composition. However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

The preferred dose of the mixed extract of Rhododendron, Elm, Centella asiatica and Licorice according to the present invention varies depending on the condition and body weight of the patient, the degree of disease, the drug form, the administration route and the period, but can be appropriately selected by those skilled in the art. However, for the desired effect, it is preferable to administer 0.01 mg / kg to 10 g / kg per day. The administration may be carried out once a day or divided into several doses. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal, or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

The composition according to the present invention can be used alone or in combination with methods for the prevention and treatment of atopic skin diseases or using surgery, hormone therapy, drug therapy and biological response modifiers.

In addition, the present invention provides an atopic cosmetic composition containing the above-mentioned mixed extract of Rhododendrons, Elm, Centella asiatica and Licorice as an active ingredient. The cosmetics prepared from the cosmetic composition for preventing and treating atopic skin diseases may be prepared in the form of a general emulsified formulation and a solubilized formulation. Cosmetics of emulsified form include nutrition lotion, cream, essence, etc., and cosmetics of solubilized form have softening longevity. In addition to cosmetics containing the herbal mixture of the present invention, elm, centipedes and licorice blended extracts, it is also possible to use a dermatologically acceptable medium or base in the form of adjuvants which can be applied locally or systemically, .

Suitable cosmetic formulations include, for example, solutions, gels, solid or kneaded anhydrous products, emulsions obtained by dispersing the oil phase in water, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) In the form of a foliar dispersant, in the form of creams, skins, lotions, powders, lozenges, sprays or conceal sticks. It can also be prepared in the form of a foam or an aerosol composition further containing a compressed propellant.

In addition, the cosmetic composition of the present invention can further contain a fatty substance, an organic solvent, a solubilizer and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance agent, Surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, lipophilic or lipophilic active agents, lipid vesicles or cosmetics Or any other ingredient conventionally used in cosmetics or dermatology. And the above ingredients may be introduced in amounts commonly used in the dermatology field.

As a specific formulation of the cosmetic composition of the present invention, there may be mentioned a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, And includes formulations such as soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, milky lotion, press powder, loose powder, eye shadow and the like.

Hereinafter, the present invention will be described in detail with reference to Production Examples, Examples and Preparation Examples. However, the following Production Examples, Examples and Preparation Examples are provided only to illustrate the present invention specifically, and the scope of the present invention is not limited by these Production Examples, Examples and Preparation Examples.

≪ Preparation Examples 1 to 5 > Preparation of rhizome, elm, cinnabar and licorice

All the haysters, elms, centipedes, and licorice were purchased from the market. Third distilled water was added at a concentration of 14 g / l, and the mixture was heated at 75 ° C for 24 hours. After that, the solids were filtered and each extract was obtained. The filtered extracts contained 2.5: 2.5: 2.5: 2.5 (Preparation Example 1), 7: 1: 1: 1 (Preparation Example 2), 1: 7: 1: 1: 1: 7: 1 (Preparation Example 3), 1: 1: 7: 1 (Preparation Example 4) and 1: 1: 1: 7 (Preparation Example 5). Each of the above-prepared mixtures was sterilized by irradiation with ⁶⁰ Co gamma rays (5 kGy / H, 25 kGy). If necessary, the lyophilized powder was dissolved in a suitable solvent and used.

≪ Production Examples 6 to 10 > Production of Allium cepa, Elm, Cinnabar and Licorice

In Preparation Example 1, 14 g of each of hay hay, elm, elk, and licorice hay was added to 1 L of 70% ethanol (water: ethanol = 30: 70) and heated to 60 DEG C for 24 hours. 2.5: 2.5: 2.5: 2.5 (Preparation Example 6), 7: 1: 1: 1 (Preparation Example 7) were mixed at a mixing ratio of water extract, 1: 7: 1: 1 (Production Example 8), 1: 1: 7: 1 (Production Example 9) and 1: 1: 1: 7 (Production Example 10) The ingredients were removed.

≪ Production Examples 11 to 15 > Production of Allium cepa, Elm, Cinnabar and Licorice

14 g of each of hay, elm, centipoise and licorice in a hay state was placed in 1 L of 80% methanol (water: methanol = 20: 80) in Production Example 1 and precipitated at 4 for 24 hours. And heated in a hot water bath. 2.5: 2.5: 2.5: 2.5 (Preparation Example 11), 7: 1: 1: 1 (Preparation Example 12) in a weight ratio of the extract of Herbaceae, elm, 1: 7: 1: 1 (Production Example 13), 1: 1: 7: 1 (Production Example 14) and 1: 1: 1: 7 (Production Example 15) The ingredients were removed.

≪ Production Examples 16 to 20 > Production of Allium cepa, Elm, Cinnabar and Licorice

The natural mixed extracts were prepared by the same method as Preparation Examples 1 to 5 except that ethyl ether was used as the extraction solvent.

≪ Production Examples 21 to 25 > Manufacture of artichoke, elm, cinnabar and licorice

The natural mixed extracts were prepared by the same method as Preparation Examples 1 to 5 except that chloroform was used as an extraction solvent.

≪ Preparation Examples 26 to 30 > Manufacture of artichoke, elm, cinnabar and licorice

The natural mixed extract was prepared by the same procedure as in Preparation Examples 1 to 5 except that ethyl acetate was used as an extraction solvent.

<Comparative Production Example 1>

Were prepared in the same manner as in Preparation Examples 1 to 5, except that the mixing ratio of Rhizoctoniaceae, Elmwood, Centella asiatica and Licorice was 100%.

<Comparative Production Example 2>

Were prepared in the same manner as in Preparation Examples 1 to 5, except that the mixing ratio of Alaska pollack, Elmwood, Centella asiatica and Licorice was 100%.

<Comparative Production Example 3>

Except that the mixture ratio of Phellodendron chinensis, Elmwood, Centella asiatica and Licorice was 100%.

<Comparative Production Example 4>

The mixture was prepared in the same manner as in Preparation Examples 1 to 5, except that the mixing ratio of liquorice, elm,

The following experiment was carried out in order to examine the effects of the above-mentioned perennials, elm, cinnabar and licorice according to the present invention.

<Example 1> Inhibitory effect on local skin inflammation reaction

Reduction of inflammation in passive skin anaphylaxis

Seven to eight week old male rats (SD Rat) were lightly anesthetized with ether, and their backs were removed to restore fine wounds during the day. After 1 day, 50 쨉 l of the mixed extracts of Preparation Examples 1 to 6 was injected into the dermis of the epidermis of the dorsal part, and after 30 minutes, 0.5 占 퐂 / site of N-methyl-p-methoxyphenethylamine (Compound 48/80, Sigma, St. Louis, Mo., USA, hereinafter referred to as "compound 48/80"). After 30 minutes, 1 mL of 1% Evans blue (Sigma, St. Louis, Mo., USA) was injected into the vein of the penis. After 30 minutes, the skin was peeled off and the degree of inhibition was visually judged Respectively. After determining the reaction, cut off the reaction site, add 5 mL of 0.1 N KOH, and add a mixture of acetone and phosphoric acid (5:13) to extract the pigment. The absorbance of the dye mixture was measured by a spectrophotometer at 620 nm and the amount of dyeing was measured with an Evans standard curve. The absorbance was shown in FIG. The control group was the untreated group and the comparative group was treated with the extracts of Comparative Preparation Examples 1 to 4.

As shown in FIG. 1, when mixed with the herbal extract, elm seedlings, centipedes and licorice extracts, the compound 48/80-induced vascular permeability was effectively reduced in mast cells, And the ratio of 2.5: 2.5: 2.5: 2.5 in terms of weight ratio showed the most significant inhibitory effect.

&Lt; Example 2 > Inhibitory effect on systemic allergic reaction

Inhibitory effect of allergic response on systemic anaphylactic shock test

The mixed extracts of Preparative Examples 1 to 6 were orally administered to female rats (BALB / C) at 7 to 8 weeks of age for five days in 200 rats per adult. After 1 hour of oral administration on the 5th day, compound 48/80 was injected intraperitoneally at 8 mg / kg to induce systemic anaphylactic shock, followed by lethality for 30 to 60 minutes. As a positive control group, compound 48/80 was used pretreated with sterilized water. Negative control group was not treated with sterilized water. As a comparative group, the extracts of Comparative Production Examples 1 to 4 were treated and used.

As shown in FIG. 2, the positive control group treated with sterilized water showed 100% mortality. However, mortality after oral administration of compound extracts for 5 days before compound 48/80 significantly decreased mortality rate. Especially, the mixing ratio of herringbone, elm, clover and licorice extract was 2.5: 2.5 : 2.5: 2.5, the inhibition of anaphylactic shock reaction was confirmed to be effective at a mortality rate of 20%.

&Lt; Example 3 > Cytotoxicity test of Rhizobium, Elm, Cinnabar and Licorice

Cytotoxicity test of mixed extracts on skin keratinocytes

Human dermal keratinocytes, HaCaT cells, were cultured in 10% FBS / DMEM. The seeds were seeded in 96-well plates at 5 × 10 ³ , and after 24 hours, 100 μl of each of the mixed extracts of Production Examples 1 to 6 was treated for 24 hours. After completion of the mixed extract treatment, the cells were reacted using a CCK-8 kit, and the cytotoxicity of the natural mixed extract was measured by measuring the absorbance at 450 nm by a spectrophotometer. The control group was the untreated group and the comparative group was the extracts of Comparative Preparation Examples 1 to 4. [

As shown in FIG. 3, when the mixed extract had a concentration of 10 μl / mL, the cell survival rate was 93 to 98%, respectively, as compared with the control, and no cytotoxicity was observed in the mixed extracts of Preparation Examples 1 to 5.

<Example 4> Inhibitory effect of inflammatory cytokines of Rhizobium, Elm,

Inhibitory effect of inflammatory cytokine on human mast cell line HMC-1

Inflammatory cytokine measurements associated with atopy were measured using a human obesity cell line (HMC-1). After inoculation the HMC-1 to 5x10 ⁵ in 24 well plate was pretreated with a mixed extract 200㎕ of Preparation 1-5 for 1 hour. After pretreatment, cells were stimulated with PMA (Phorbol-12-myristate-13-acetate) 0.05 mM and A23187 1 mM for 7 hours. IL-6, IL-8 and TNF- a was measured. The ELISA kit was used for the measurement and the results obtained are shown in FIGS. 4, 5 and 6, respectively. As a positive control group, compound 48/80 was used pretreated with sterilized water. Negative control group was not treated with sterilized water. As comparative groups, the extracts of Comparative Production Examples 1 to 4 were used.

4, the IL-6 secretion of the control group was significantly increased in the mast cell line stimulated with PMA plus A23187 (PMACI) compared with the normal cell group. However, in the experimental group stimulated with PMACI after pretreatment with the mixed extracts of Preparation Examples 1 to 5, the secretion of IL-6 in HMC-1 was remarkably reduced. Particularly, the group treated with the extracts was more strongly inhibited than the group treated with the extract alone, the elm, the elm, the cinnabar and the licorice extract, and the mixing ratio of the mixed extracts was 2.5 : 2.5: 2.5: 2.5, the expression of IL-6 is suppressed by about 80% or more.

Referring to FIG. 5, the results of IL-8 show that IL-8 inhibition is more excellent in the case where the extracts are mixed with each other than the case where the extracts of Alaska pollack, elm tree, Centella asiatica and licorice extract are treated alone. In particular, when the mixing ratio of the mixed extract is 2.5: 2.5: 2.5: 2.5 at a weight ratio, it can be seen that the inhibitory effect is about 35% or more.

Referring to FIG. 6, the inhibitory effect of IL-6 and IL-8 was similar to that of mixed extracts. In particular, it can be seen that when the mixing ratio of the herbicide, elm, cucumber and licorice extract is 2.5: 2.5: 2.5: 2.5 by weight ratio, the mixture exhibits an inhibitory effect of about 60%.

Examples of formulations for the composition of the present invention are illustrated below.

&Lt; Formulation Example 1 > Preparation of powders

The ingredients shown in Table 1 below were mixed and filled in an airtight container to prepare powders.

Raw material Content (mg) Allium cepa, elm, cinnabar and licorice 20 Lactose 100 Talc 10

&Lt; Formulation Example 2 > Preparation of tablet

After mixing the ingredients shown in Table 2 below, tablets were prepared by tableting according to the usual preparation method of tablets.

Raw material content( mg ) Allium cepa, elm, cinnabar and licorice 10 Corn starch 100 Lactose 100 Magnesium stearate 2

&Lt; Formulation Example 3 > Preparation of capsules

The ingredients shown in the following Table 3 are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Raw material Content (mg) Allium cepa, elm, cinnabar and licorice 10 Crystalline cellulose 3 Lactose 14.8 Magnesium stearate 0.2

&Lt; Formulation Example 4 > Preparation of injection

(2 mL) per 1 ampoule according to the usual injection preparation method.

Raw material Content (mg) Allium cepa, elm, cinnabar and licorice 10 Mannitol 180 Sterile sterilized water for injection 2974 Na ₂ HPO _{4 12} H ₂ O 26

&Lt; Formulation Example 5 > Preparation of cosmetics

<5-1> Production of flexible lotion

To the purified water was added a mixture prepared by adding butylene glycol, glycerin, polyoxyethylene (60) hardened castor oil, betaine, citric acid, sodium citrate and an antiseptic, stirring and dissolving, followed by dissolving the perfume in ethanol. Then, the mixture was thoroughly stirred, and then the mixture was aged to prepare a flexible lotion containing the mixed extract according to the present invention. The content of each component is shown in Table 5 below.

Raw material Content (w / w%) Allium cepa, elm, cinnabar and licorice 25.0 Butylene glycol 3.5 glycerin 2.5 Polyoxyethylene (60) Hardened castor oil 0.1 ethanol 2.5 Betaine 1.0 Citric acid 0.01 Sodium citrate 0.03 antiseptic a very small amount Spices a very small amount Purified water Balance

<5-2> Production of nutrition lotion

The herringbone, elm, centipoise, licorice, butylene glycol, glycerin, carboxyvinyl polymer, arginine, preservative and purified water according to the present invention were heated at 70 to 75 캜 with stirring. After adding a mixture of squalane, butylene glycol dicaprylate / dicaprate, sorbitan stearate, porisorbate 60, glyceryl stearate and stearyl glycerate, heated at 75 to 80 ° C with stirring, emulsified, The mixture was cooled to about 45 캜 while stirring, and the mixture was stirred. After cooling to 30 캜, the mixture was aged to prepare a nutritional lotion containing the mixed extract according to the present invention. The content of each component is shown in Table 6 below.

Raw material Content (w / w%) Allium cepa, elm, cinnabar and licorice 40.0 Butylene glycol 8.0 glycerin 5.0 Squalane 10.0 Butylene glycol dicaprylate / dicaprate 5.0 Sorbitan stearate 1.5 Polysorbate 60 1.0 Glyceryl stearate 0.5 Stearyl glycyrrhetinate 0.2 Carboxyvinyl polymer 0.1 Arginine 0.1 antiseptic a very small amount Spices a very small amount Purified water Balance

<5-3> Production of essence

Polyglyceryl-2-olate, ceramide, cetearase-4 and cholesterol are mixed with stirring, and then the mixture of cytociterol, polyglyceryl-2-olate, ceramide, The resulting mixture was stirred and mixed. Then, the resulting mixture was emulsified by adding a mixture solution of the herb of the present invention, elm, cinnabar, licorice, dicetylphosphate, concentrated glycerin and purified water. The mixture was stirred at 45 ° C, RTI ID = 0.0 &gt; C &lt; / RTI &gt; Carboxyvinyl polymer, xanthan gum and preservative were added to the mixture to stabilize it, followed by aging to prepare an essence containing the mixed extract according to the present invention. The content of each component is shown in Table 7 below.

Raw material Content (w / w%) Allium cepa, elm, cinnabar and licorice 10.0 Sitosterol 1.7 Polyglyceryl-2-olate 1.5 Ceramide 0.7 Setares-4 1.2 cholesterol 1.5 Dicetyl phosphate 0.4 Concentrated glycerin 5.0 Carboxyvinyl polymer 0.2 Xanthan gum 0.2 antiseptic a very small amount Spices a very small amount Purified water Balance

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention. The present invention is not limited to the drawings.

Claims (17)

A pharmaceutical composition for preventing and treating atopic skin diseases, comprising as an active ingredient, a mixed extract of Rhizobium, Elm, Cinnabar, and Licorice.
The method according to claim 1,
The pharmaceutical composition for prevention and treatment of an atopic skin disease according to claim 1, wherein the perennial herb extract and licorice extract are respectively extracted from leaf, stem, root or a mixture of two or more thereof.
The method according to claim 1,
Wherein the elm extract is extracted from leaf, stem, root or elm of two or more of the leaves of the elm, and the composition is for prevention and treatment of atopic skin disease.
The method according to claim 1,
Wherein the elm extract is extracted from the stem or stem and the bark of the root, and the composition is for preventing and treating atopic skin disease.
The method according to claim 1,
Wherein said Centella asiatica extract is obtained by extracting leaves of a Centella asiatica.
The method according to claim 1,
The above-mentioned mixed extract is characterized in that the elongase extract, the elm seed extract, the centilla callus extract and the licorice extract comprise 10 to 80% by weight of the rhizome, 5 to 65% by weight of the elm, 5 to 65% Or a pharmaceutically acceptable salt thereof, for the prophylaxis and treatment of atopic skin diseases.
The method according to claim 6,
The elm extract, elm seed extract, licorice extract and licorice extract of the above-mentioned mixed extract are 10-50% by weight of the rhizome, 10-40% by weight of the elm, 10-40% by weight of the centipede and 5-30% A pharmaceutical composition for preventing and treating atopic skin diseases.
The method according to claim 1,
The pharmaceutical composition for prevention and treatment of atopic skin diseases, wherein the extracts of Hwasung juice, elm seedlings, centilla sp., And licorice root extract are hydrothermal extract, alcohol extract or organic solvent extract.
Wherein the hot-water extract is a tertiary distilled water extract, and the pharmaceutical composition for preventing and treating atopic skin disease.
9. The method of claim 8,
Wherein the alcohol extract is a C ₁ -C ₄ alcohol or a mixed extract thereof.
9. The method of claim 8,
Wherein the organic solvent extract is ethyl ether, chloroform, ethyl acetate or a mixed extract thereof.
The method according to claim 1,
The pharmaceutical composition for preventing and treating atopic skin diseases, wherein the mixed extract is sterilized by irradiation.
The method according to claim 1,
A pharmaceutical composition for preventing and treating atopic skin diseases, wherein the composition inhibits local skin inflammatory reaction.
The method according to claim 1,
Wherein said composition inhibits systemic atopic response. &Lt; RTI ID = 0.0 &gt; 11. &lt; / RTI &gt;
The method according to claim 1,
Wherein said composition inhibits the secretion of inflammatory cytokines.
The method according to claim 1,
Wherein the atopic skin disease is selected from the group consisting of atopic dermatitis, psoriasis, contact atopic dermatitis, and urticaria.
A cosmetic composition for preventing and treating atopic skin diseases, which comprises the mixed extract of any one of claims 1 to 16 as an active ingredient.

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