KR20090084435A - Pharmaceutical composition for the prevention and treatment of allergic skin diseases containing extract of houttuynia cordata thub and ulmus davidana var.japonica as an active ingredient - Google Patents

Abstract

A pharmaceutical composition for preventing and treating allergic skin disorder is provided to suppress topical inflammation and inflammatory cytokine using a Houttuynia Cordata Thunb and Ulmus davidana var.Japonica. A pharmaceutical composition for preventing and treating allergic skin disorder comprises a mixed extracts of Houttuynia Cordata Thunb and Ulmus davidana var.Japonica as an active ingredient. The Houttuynia Cordata Thunb is obtained from leaves, stem, root or their mixture of Houttuynia Cordata Thunb. The extract of Houttuynia Cordata Thunb and Ulmus davidana var. Japonica is extracted using hot water, alcohol, or organic solvent. The allergic skin disorder is selected from atopic dermatitis, psoriasis, contact allergic dermatitis and urticaria.

Description

Pharmaceutical composition for the prevention and treatment of allergic skin diseases containing extract of Houttuynia Cordata Thub and Ulmus davidana var.Japonica as an active ingredient}

The present invention relates to a pharmaceutical composition for preventing and treating allergic skin diseases, which contains Echo and Elm as an active ingredient.

Atopy, atopia in Latin, is an odd word, meaning a constitution that is prone to hypersensitivity. Atopy causes a series of allergic symptoms in the skin, respiratory mucosa, eye mucosa, and intestinal mucosa of people with atopic inducers. People with atopic inducers often have urticaria reactions in skin tests for protein substances frequently encountered in the external environment, such as house dust, mites, animal hair, food, pollen, and fungi, and when eating or inhaling certain protein substances, Symptoms include itching, skin attacks, hives, angioedema, sneezing, runny nose, stuffy nose, conjunctival hyperemia, and tears. Atopic inducers causing these symptoms are inherited and appear to be family. Allergic skin diseases caused by atopy-inducing factors include atopic dermatitis, allergic rhinitis, asthma, allergic conjunctivitis, allergic enteritis, and atopic urticaria. These diseases include genetic predisposition, environment, and age of each patient. May appear alone or in combination at the same time. Among them, atopic dermatitis is a typical allergic skin disease in people with atopic allergy.

The blood and skin histological findings of atopic dermatitis patients show that IgE and monocytes have increased IgE receptor I expression and auxiliaries, and the skin has an increase in IgE receptor-expressing antigen-transmitting cells, activated T cells, IL-5, IL-10, IL-13 and eosinophils are elevated. Patients with atopic dermatitis show immunological adverse reactions: increased immediate-type hypersensitivity to environmental antigens, increased IgE and IgE receptor expression, increased antigen-specific T cells and Th2 cells, and when the disease becomes chronic, Th1 cells An increasing binary cytokine profile is shown. In addition, epidermal Langerhans cells and memory T cells are activated, dendritic cells, eosinophils, and mast cells are activated.

Atopic dermatitis begins with infant eczema, commonly referred to as febrile fever, with itching in the acute phase, reddening, swelling, or millet-like growth, small blisters, moist scabs, and itching in chronic periods. Symptoms may include stiffening, thickening, thinning, scales such as rice flour, sitting, blackening, or whitening.

In view of the etiology, mechanisms, and symptoms of atopic dermatitis as described above, the development of therapeutic agents for the skin diseases is actively progressed. As a result, natural or synthetic immunosuppressants, steroids, and antihistamines have been developed. .

However, conventional steroids used as a treatment for atopic dermatitis have side effects such as hair growth, skin atrophy, reduction of skin pigment, bacterial infections, acne production, skin thinning, and dermal growth of the skin when applied for a long time. In severe cases, hormonal systemic symptoms may occur, and when the use of the skin disease treatment agent is stopped, symptoms may suddenly worsen and the use of the treatment agent may not be stopped. In most cases, systemic administration of the adrenal cortex is not recommended because the development of atopic dermatitis occurs in infants before the age of five. Therefore, steroid ointment with very low hormone concentration should be used only when it is necessary for a short time and should be used frequently instead of applying large amount at once.

In addition, conventional antihistamines, which are used as treatments for atopic dermatitis, are used as a temporary measure to prevent histamine from being released from mast cells, which may relieve itching symptoms, but may cause side effects such as insomnia, anxiety, and loss of appetite. .

In view of the characteristics of atopic dermatitis, the most effective alleviation and treatment of atopic dermatitis is the suppression of systemic allergic reactions, especially the expression of inflammatory cytokines.

On the other hand, Eoseongcho is a perennial herb that belongs to more than three hundred in plant classification, and its scientific name is Houttuynia Cordata. It is called Thub . The natural product has an antibacterial effect, and has effects such as anti-inflammatory, analgesic, and tissue regeneration. The Korean Encyclopedia consists of medicinal buckwheat and has ten kinds of medicinal benefits. It is called medicinal because it is boiled in order to eat herbs, Chinese medicine, and young when they are young. They have 30 kinds of tinnitus. do. It is widely distributed from Himalayas, China, Japan, Korea, and East Asia to Eurasia. In Korea, it is wild on Jeju Island, Ulleungdo and Anmyeondo, and is also grown on farms. It grows well under lowland restoration or on the wet side of the roadside. The underground diameter extends long and the ground diameter is upright and grows about 20-50 cm in height. The whole has a peculiar smell that is soft or injured. Two of these volatile components, undecanone and decanoly acetaldehyde, are thought to play an important role in fishy fish's unique fishy smell. Efficacy of Eoseongcho is called 'blood clotting antidote' because it prevents blood and eliminates poison. It is used to treat blue blood detoxification, edema, paralysis, pneumonia, bandage, eczema, otitis media and hypertension. It has strong antibacterial effect. In fact, it is known that antiviral activity against katharrh cocci and influenza type A is excellent, as well as diuretic, cardiovascular, hypertension and capillary strengthening.

Also, elm ( Ulmus davidiana var . Japonica ) is a deciduous broad-leaved arborescent of the dicotyledonous plant Nettle, Elmaceae, distributed in Korea, Japan, Sakhalin, Kuril Islands, northern China and East Siberia. . There are many varieties of elm, but the shape of leaves and their use as medicine are the same. These elm trees have long been used as a diuretic, hygienic or boil treatment. Medicines include elm root bark, which contains flavonoids, saponins (hemolytic index 1: 1900), tannins (3%), or large amounts of mucus. The elm root bark has been reported to enhance the movement of the small intestine and bladder smooth muscle, to cough up, astringent and anti-inflammatory. It is reported that it is effective to treat various skin diseases and to make skin beautiful and smooth when it is eaten or applied to the skin of elm root bark. Elm root bark has also been reported to have an excellent effect on gastric ulcer, duodenal ulcer, small intestine ulcer, and colon ulcer. Elm leaves, on the other hand, act as a natural sleeping pill without side effects, and elm berries have an antiparasitic and antibacterial effect.

Conventionally, the extract of Echochocho or mixed extract of Echochocho and other plants has been reported to be effective in atopic skin diseases, but the extract of Echochocho and Elm has excellent effects on allergic skin diseases including atopic dermatitis. It has not been reported yet.

Thus, the present inventors have a systemic allergic inflammatory response, local inflammatory response and inflammatory cytokine expression found in patients with atopic dermatitis than the composition containing the Echo and Elm extract alone The present invention has been accomplished by finding that symptoms can be improved overall and effectively.

The present invention is to provide a pharmaceutical composition for the prevention and treatment of allergic skin diseases containing Echo herb and elm mixed extract as an active ingredient.

The present invention also provides a cosmetic composition for the prevention and treatment of allergic skin diseases containing the mixed extract as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition or a cosmetic composition for the prevention and treatment of allergic skin diseases, which contains a mixture of Echo and Elm mixed extract in a predetermined mixing ratio as an active ingredient.

Echo herb and elm mixed extract according to the present invention is almost non-toxic, exhibits the prevention and treatment of allergic skin diseases caused by anti-inflammatory and anti-allergic effects, allergic inflammation when mixed at an appropriate ratio compared to the application alone, respectively. It contains the mixed extract as an active ingredient because it has an excellent effect on suppressing the reaction, systemic allergic inflammatory reaction, local inflammatory reaction and inflammatory cytokine expression, and has an excellent effect on allergic skin diseases including atopic dermatitis. The pharmaceutical composition may be usefully used for preventing and treating allergic skin diseases.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

The present invention provides a pharmaceutical composition for preventing and treating allergic skin diseases, which contains Echo and Elm mixed extract as an active ingredient.

In the composition according to the present invention, it is preferable to use the extract from the leaves, stems, roots or a mixture of two or more of them. Among these, the leaves or leaf and stem extracts of fish vinegar are more preferable.

In addition, in the composition according to the present invention, the elm extract is preferably used by extracting a mixture of two or more leaves, stems, roots or these from the elm. Among them, the stem or stem and root extract of the elm tree is more preferable.

In the composition according to the present invention, the mixing ratio of the Echo extract and elm extract of the mixed extract is preferably 9: 1 to 1: 9. If it is outside the range of the mixing ratio, there is no significant difference in terms of allergic reactions or inflammatory response as compared to the case of using Echo extract or elm extract alone. Furthermore, it is more preferable that the said mixing ratio is 8: 2-5: 5, and it is most preferable that it is 7.5: 2.5-6.5: 3.5. At the above composition ratios, the inhibitory effect of inflammatory cytokines is best.

The Echo vinegar or elm extract according to the present invention can be used according to the methods well known in the art or commercially available. In addition, Echo and elm can be used without limitation, such as cultivated or commercially available, and cleanly used. The dried fish and elm are crushed to an appropriate size and placed in an extraction container, and an appropriate amount of distilled water, alcohol or organic solvent is added. After extracting it for 24 hours or more at a suitable temperature, it is filtered through a filter paper and the like to obtain a hot water extract, an alcohol extract or an organic solvent extract according to the present invention.

Preferably, the hot water extract uses distilled water as an extraction solvent, and more preferably, uses tertiary distilled water. When hot water extraction is preferably heated for 24 hours at a temperature of 65 ~ 80 ℃.

The alcohol extract is preferably C ₁ ~ C ₄ alcohol as the extraction solvent, it is more preferable to use methanol, ethanol or a mixed solvent thereof.

The organic solvent extract is preferably ethyl ether, chloroform, ethyl acetate or a mixed solvent thereof, and can be extracted by heating in a hot water in the same manner as in the hydrothermal extract.

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

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

The pharmaceutical composition according to the present invention can be usefully used for the prevention and treatment of allergic skin diseases such as atopic dermatitis, psoriasis, contact allergic dermatitis, urticaria.

When the skin is exposed to allergens, antigen-specific IgE binds to the IgE receptor on the surface of Langerhans cells and is delivered to T cells on the surface of the antigen to activate T cells. In this case, unlike normal, allergic skin diseases, in particular, atopic dermatitis Th2 is activated to secrete cytokines such as IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, As a result, the production of IgE in B cells is promoted, and the degranulation of activated mast cells is promoted, thereby releasing inflammatory cytokines and histamine (Baruah CC et al., Pharmacol Res. 1998, 38, 487-492; Karadag CH et al., Braz. J. Med. Biol. Res. 2000, 33, 327-330; Paolini R. et al., Nature. 1991, 353, 855-858).

Inhibitory effect measured by applying the extracts alone from an experiment measuring the inhibitory effect on the inflammatory cytokines IL-6 and IL-8 of Eochocho and elm mixed extracts included as an active ingredient of the composition according to the present invention It can be seen that when measured by applying these mixed extracts exhibits a very good inhibitory effect. In particular, it can be seen that this inhibitory effect largely depends on the mixing ratio of these extracts (see Example 4, Figures 5 and 6 ).

In addition, by using the mixed extract of Echo and elm tree extract as an active ingredient of the composition according to the present invention to promote the adhesion of leukocytes to vascular endothelial cells in the inflammatory response, increase the microbial apoptosis ability of inflammatory cells, mononuclear phagocytes (Mononuclear phagocytes) to produce cytokines involved in various inflammatory reactions by measuring the inhibitory effect on TNF-α that promotes the inflammatory response than those measured by applying each of these extracts alone When measured by applying a mixed extract of it can be seen that it shows a very good effect of inhibiting TNF-α expression. This inhibitory effect can be seen that the same as in the case of IL-6 and IL-8 described above shows the aspect that depends on the mixing ratio of the mixed extract (see Example 4 and Figure 4 ).

In addition, Echo and Elm mixed extracts included as an active ingredient of the composition according to the present invention is vascular permeability by the compound 48/80 in mast cells from the results of experiments to determine whether the inhibition of local dermatitis and systemic allergic reactions the reduced effective (example 1 and Fig. 1), systemic know it can be seen that peel lactic Sikkim hence decrease (30%) compared to the mortality of the shock in response to a positive control (100%) (examples 2 and 2 Reference).

Therefore, the pharmaceutical composition according to the present invention can be usefully used for preventing and treating allergic skin diseases.

The pharmaceutical composition of the present invention having a prophylactic and therapeutic effect of allergic skin diseases is conventionally prepared by including the extract of Echo and Elm alone, or by additionally including one or more pharmaceutically acceptable carriers, excipients or diluents. It can be formulated in a phosphorous method.

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

The pharmaceutical composition of the present invention may be formulated into a formulation for oral administration or parenteral administration according to the selected route of administration, and when formulated, fillers, weight agents, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used It is prepared using diluent or excipient. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose and the like. (Sucrose) or lactose (Lactose), gelatin, etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, syrups, and the like, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be used. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspending solvent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like can be used. Witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerogelatin, and the like may be used as the base of the suppository.

Echo and elm mixed extract according to the invention is preferably included in 0.1 to 50% by weight relative to the total weight of the composition. However, the composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient, the type of disease, and the degree of progression.

Preferred dosages of the mixture of Echo and Elm according to the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, it is good to administer at 0.01 mg / kg to 10 g / kg per day. Administration may be administered once a day or may be divided several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal, or intravenous, intramuscular, subcutaneous, intrauterine dural or Intracerebroventricular injection.

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

In addition, the present invention provides a cosmetic composition containing the above-mentioned Echo and elm mixed extract as an active ingredient.

Cosmetics prepared from the cosmetic composition for the prevention and treatment of allergic skin diseases can be prepared in the form of a general emulsion formulation and solubilized formulation. Cosmetics of the emulsified formulations include nutrient cosmetics, creams, essences, etc., and cosmetics of the solubilized formulations are flexible cosmetics. In addition, cosmetics containing the mixed extract of Echo and elm of the present invention can be prepared in the form of adjuvants that can be applied topically or systemically as commonly used in the field of dermatology by containing a dermatologically acceptable medium or base. .

Formulations of suitable cosmetics include, for example, emulsions, suspensions, microemulsions, microcapsules, microgranules or ionics (liposomes), nonionics, obtained by dispersing an oil phase in a solution, gel, solid or pasty anhydrous product, aqueous phase. Can be provided in the form of a vesicle dispersant, cream, skin, lotion, powder, haze, spray or conceal stick. It may also be prepared in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

In addition, the cosmetic composition of the present invention, in addition to Echo and Elm mixture extract, fatty substances, organic solvents, solubilizers and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, Commonly used in water, ionic or nonionic emulsifiers, fillers, metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics And any other ingredients that may be used, such as auxiliaries commonly used in the cosmetic or dermatological arts. And the above ingredients may be introduced in amounts generally used in the field of dermatology.

Specific formulations of the cosmetic composition of the present invention include skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, nutrition essence, pack, Formulations such as soaps, shampoos, cleansing foams, cleansing lotions, cleansing creams, body lotions, body cleansers, emulsions, press powders, loose powders, eye shadows and the like.

Hereinafter, the present invention will be described in detail through production examples, examples and formulation examples. However, the following Preparation Examples, Examples and Formulation Examples are provided only to specifically describe the present invention, but the scope of the present invention is not limited by these Preparation Examples, Examples and Formulation Examples.

< Production Example  1 ~ 6> Preparation of Eotseongcho and Elm Tree Extracts

All of the hay and elm in the hay were purchased on the market and heated to 75 ° C. for 24 hours after the addition of tertiary distilled water at a concentration of 14 g / 1 L, respectively. After filtering the solids, each extract was obtained. The filtered extracts had a ratio of Echo and Elm extracts of 9: 1 (Preparation Example 1), 8: 2 (Preparation Example 2), 7: 3 (Preparation Example 3), 5: 5 (Preparation Example 4), 3: 7 (Preparation Example 5) and 2: 8 (Preparation Example 6) were mixed to prepare a mixed extract. Each of the prepared mixtures was irradiated and sterilized with ⁶⁰ Co gamma rays (5 kGy / H, 25 kGy). If necessary, the freeze-dried powder was used in a suitable solvent.

< Production Example  7 ~ 12> Preparation of Eotseongcho and Elm Tree Extracts

In Preparation Example 1, 14 g of each of the vinegar or elm tree in the hay state was put in 1 L of 70% ethanol (water: ethanol = 30:70), and heated at 60 ° C. for 24 hours. Thereafter, the solids were filtered off, and the remaining extracts were mixed so that the ratio of Eochocho and elm extract was 9: 1, 8: 2, 7: 3, 5: 5, 3: 7 and 2: 8, and then using a vacuum evaporator. The alcohol component was removed.

< Production Example  13 ~ 18> Preparation of Eotseongcho and Elm Tree Extracts

In Preparation Example 1, 14 g of each of the hay vinegar or elm tree in the hay state was put in 1 L of 80% methanol (water: methanol = 20: 80), precipitated at 4 ° C. for 24 hours, and then heated at 95 ° C. for 6 hours. It was. Thereafter, the solids were filtered off, and the remaining extracts were mixed so that the ratio of Eochocho and elm extract was 9: 1, 8: 2, 7: 3, 5: 5, 3: 7 and 2: 8, and then using a vacuum evaporator. The alcohol component was removed.

< Production Example  19 ~ 24> Preparation of Eotseongcho and Elm Tree Extracts

Except for using ethyl ether extract solvent was prepared in the same manner as in Preparation Examples 1 to 6 to prepare the natural mixed extract.

< Production Example  25 ~ 30> Preparation of Eotseongcho and Elm Tree Extracts

The natural mixed extract was prepared in the same manner as in Preparation Examples 1 to 6, except for using chloroform as the extraction solvent.

< Production Example  31 ~ 36> Preparation of Eotseongcho and Elm Tree Extracts

The natural mixed extract was prepared in the same manner as in Preparation Examples 1 to 6, except for using ethyl acetate.

< Comparative Production Example  1>

It was prepared in the same manner as in Preparation Examples 1-6 except that the mixing ratio of Eoseongcho and Elm mixed extract was 10: 0.

< Comparative Production Example  2>

It was prepared in the same manner as in Preparation Examples 1 to 6 except that the mixing ratio of Eoseongcho and Elm mixed extract was 0:10.

In order to determine the effect of the Echo and elm mixed extract according to the present invention was carried out the following experiment.

< Example  1> Inhibitory effect of local skin inflammation

Manual skin In anaphylaxis  Inflammation reduction effect

7 to 8 week old male rats (SD Rat) were lightly anesthetized with ether, and then back-hair was removed to recover the micro-wounds for one day. After one day, anesthesia was performed with ether, and 50 μL of the mixed extract of Preparation Examples 1 to 6 was injected into the epidermis of the depilated dorsal portion, and 30 minutes later, N-methyl-p-methoxyphenethylamine and 0.5 μg / site. Polyaldehydes of formaldehyde (compound 48/80, Sigma, St. Louis, MO, USA, hereinafter referred to as “compound 48/80”) were injected. 30 minutes later, 1 mL of 1% Evans blue (Sigma, St. Louis, MO, USA) is injected into the vein of the penis, and after 30 minutes, the skin of the dorsal part is removed and the degree of inhibition is visually determined. It was. After visual determination, the reaction site was cut and 5 mL of 0.1 N KOH was added, and then acetone and phosphoric acid (5:13) were added to extract a pigment. The absorbance of the pigment mixture is measured in a spectrophotometer 620 nm and is shown in Figure 1 by measuring the amount of staining with the Evans standard curve (Evans standard curve). As a control group, an untreated group was used, and a comparative group was used by treating the extracts of Comparative Preparation Examples 1 and 2.

As shown in Fig. 1 , the extracts from Echo and elm extracts effectively reduced vascular permeability by compound 48/80 in mast cells, especially the ratio of Echo and elm extracts. In the case of 7: 3, the most significant inhibitory effect was confirmed.

< Example  2> systemic allergic reaction inhibitory effect

Systemic Anaphylactic  Inhibitory effect of allergic reaction in shock test

7-8 weeks old female rats (BALB / C) was administered orally administered the mixed extract of Preparation Examples 1-6 for 5 days at 200 μL per horse. After 1 hour of oral administration on the last 5 days, compound 48/80 was intraperitoneally injected at 8 mg / kg to induce systemic anaphylactic shock, and death was observed for 10-15 minutes. As a positive control, a compound 48/80 was used as a pretreatment of sterile water, and as a negative control, a sterile water was not used. In addition, the comparative group was used by treating the extracts of Comparative Preparation Examples 1 and 2.

As shown in FIG. 2 , the positive control pretreated with sterile water showed 100% mortality. However, mortality was significantly decreased after oral administration of the mixed extract for 5 days prior to compound 48/80, and the mortality rate was significantly reduced, especially when the ratio of Echo and Elm extract was 7: 3. Effective anaphylactic shock response inhibition was confirmed.

< Example  3> Cytotoxicity Test of Echinacea and Elm Extracts

Dead skin cells  Cytotoxicity Test of Mixed Extracts on Progenitor Cells

HaCaT cells, which are human keratinocytes, were cultured with 10% FBS / DMEM. After seeding 5 × 10 ³ in a 96 well plate and 24 hours later, 100 μL of the mixed extract of Preparation Examples 1 to 6 was treated for 24 hours. After completion of the mixed extract treatment, the reaction was performed using a CCK-8 kit, and the absorbance was measured at 450 nm of the spectrophotometer to measure the cytotoxicity of the natural mixed extract. As a control group, an untreated group was used, and as a comparative group, extracts of Comparative Preparation Examples 1 and 2 were used.

As shown in FIG. 3 , when the mixed extract had a concentration of 10 μg / mL, the cell viability was 93-98%, respectively, compared to the control group, and cytotoxicity was not observed in the mixed extracts of Preparation Examples 1-6.

< Example  4> Inflammatory Cytokine Inhibitory Effect of Echinacea and Elm Extracts

Human mast cell line HMC -1 Inhibitory Effect on Inflammatory Cytokine Secretion

Inflammatory cytokine measurements associated with atopy were measured using a human mast cell line (HMC-1). After inoculating HMC-1 on a 24 well plate at 5 × 10 ⁵ , 200 μL of the mixed extract of Preparation Examples 1 to 6 was pretreated for 1 hour. After pretreatment, stimulation with POM (Phorbol-12-myristate-13-acetate) 0.05 mM and A23187 1 mM for 7 hours and centrifugation resulted in representative inflammatory cytokines IL-6, IL-8, TNF- α was measured. As a measuring method, an ELISA kit was used, and the results obtained from the measurement are shown in FIGS . 4 , 5, and 6 , respectively. As a positive control, a compound 48/80 was used as a pretreatment of sterile water, and as a negative control, a sterile water was not used. In addition, the extract of Comparative Preparation Examples 1 and 2 was used as a comparative group.

Referring to FIG. 4 , TNF-α secretion of the control group was significantly increased in the mast cell line of humans stimulated with PMA plus A23187 (PMACI) compared to the normal cell group. However, in the experimental group stimulated with PMACI after pretreatment with the mixed extracts of Preparation Examples 1-6, TNF-α secretion was significantly reduced in HMC-1. In particular, the group treated by mixing the extracts than the group treated with Eoseongcho or elm extract alone showed a stronger inhibition, wherein the mixing ratio of the mixed extract is 7: 3 Preparation Example 3 (f In the case of), it can be seen that the expression of TNF-α is suppressed by about 60% or more.

Referring to FIG. 5 , the results of IL-6 were also superior to the IL-6 inhibitory effect when the extracts were treated by mixing the extracts (d ~ i) than when the Echo extract or Elm extract was treated alone (c, j). It can be seen. In particular, it can be seen that in the case of Preparation Example 3 in which the mixing ratio of the mixed extract is 7: 3, an inhibitory effect of about 80% or more is shown.

Referring to Figure 6, similar to the inhibitory pattern of TNF-α and IL-6 showed a good IL-8 inhibitory effect in the case of the mixed extract. In particular, it can be seen that in the case of Preparation Example 3 (f) and Preparation Example 4 (g) in which the mixing ratio of Eochocho and Elm extract is 7: 3 and 5: 5, it showed an inhibitory effect of about 35%.

Examples of preparations for the compositions of the present invention are illustrated below.

< Formulation example  1> Powder  Produce

The powders are prepared by mixing the ingredients shown in Table 1 below and filling them in airtight cloths.

Raw material content( mg ) Echo and Elm Extracts 20 Lactose 100 Talc 10

< Formulation example  2> Preparation of Tablet

The tablets are prepared by mixing the components shown in Table 2 below and then tableting according to a conventional method for preparing tablets.

Raw material content( mg ) Echo and Elm Extracts 10 Corn starch 100 Lactose 100 Magnesium Stearate 2

< Formulation example  3> Preparation of capsule

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

Raw material content( mg ) Echo and Elm Extracts 10 Crystalline cellulose 3 Lactose 14.8 Magnesium stearate 0.2

< Formulation example  4> Preparation of Injection

According to the conventional method for preparing an injection, it is prepared in an ingredient amount shown in Table 4 per ampule (2 mL).

Raw material content( mg ) Echo and Elm Extracts 10 Mannitol 180 Sterile Distilled Water for Injection 2974 Na ₂ HPO ₄ 12H ₂ O 26

< Formulation example  5> Manufacture of cosmetics

<5-1> Preparation of flexible lotion

Butylene glycol, glycerin, polyoxyethylene (60) cured castor oil, betaine, citric acid, sodium citrate, and preservatives were added to the purified water, followed by stirring and dissolving. After adding a mixture of Echo and elm tree extract according to the present invention, the mixture was sufficiently stirred, and aged to prepare a flexible lotion containing the mixed extract according to the present invention. Table 5 shows the content of each component.

Raw material Content (w / w%) Echo and Elm Extracts 25.0 Butylene Glycol 3.5 glycerin 2.5 Polyoxyethylene (60) hardening 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 Remaining amount

<5-2> Preparation of nutritional lotion

Echo herb and elm mixed extract, butylene glycol, glycerin, carboxyvinyl polymer, arginine, preservative and purified water according to the present invention were heated with stirring at 70 ~ 75 ℃. Squalane, butylene glycol dicaprylate / dicaprate, sorbitan stearate, polysorbate 60, glyceryl stearate, and stearyl glycerate mixture, which were heated by stirring at 75 to 80 ° C. were added thereto, followed by emulsification. While stirring to add a fragrance while cooling to about 45 ℃ while stirring, and then cooled to 30 ℃ and aged to prepare a nutrient cosmetics containing the mixed extract according to the present invention. Table 6 shows the content of each component.

Raw material Content (w / w%) Echo and Elm Extracts 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 Carboxy Vinyl Polymer 0.1 Arginine 0.1 antiseptic a very small amount Spices a very small amount Purified water Remaining amount

<5-3> Preparation of Essence

Cytocyterol, polyglyceryl-2-oleate, ceramide, ceteareth-4 and cholesterol are stirred and mixed, followed by cytocyterol, polyglyceryl-2-oleate, ceramide, ceteareth-4 and cholesterol. After mixing by stirring, emulsified by adding a mixed solution of Echo and elm tree extract, dicetyl phosphate, concentrated glycerin and purified water according to the present invention, and then cooled to 45 ℃ while stirring, adding flavoring and stirring up to 30 ℃ Cooled and aged. Carboxyvinyl polymer, xanthan gum and preservatives were added thereto, stabilized, and aged to prepare an essence containing the mixed extract according to the present invention. Table 7 shows the content of each component.

Raw material Content (w / w%) Echo and Elm Extracts 10.0 Cytostolol 1.7 Polyglyceryl-2-oleate 1.5 Ceramide 0.7 Ceteares-4 1.2 cholesterol 1.5 Dicetylphosphate 0.4 Concentrated glycerin 5.0 Carboxy Vinyl Polymer 0.2 Xanthan Gum 0.2 antiseptic a very small amount Spices a very small amount Purified water Remaining amount

1 is the Evans standard curve (a: control group, b: Comparative Preparation Example 1, c: Preparation Example 1, d: Preparation Example 2, e) Production Example 3, f Production Example 4, g Production Example 5, h Production Example 6, i: Comparative Production Example 2),

Figure 2 is a table showing the mortality obtained by measuring the systemic allergic reaction inhibitory effect of Echochocho and Elm mixture according to the present invention,

Figure 3 is a graph showing the cell viability obtained through the cytotoxicity test of the mixture of Echo and elm according to the present invention (a: control, b: Comparative Preparation Example 1, c: Preparation Example 1, d: Preparation Example 2, e: Production Example 3, f: Production Example 4, g: Production Example 5, h: Production Example 6, i: Comparative Production Example 2),

Figure 4 is a graph showing the inhibitory effect on IL-6 in inflammatory cytokines of Echochocho and Elm mixture according to the present invention (a: positive control, b: negative control, c: Comparative Preparation Example 1, d: Preparation Example 1 , e: manufacture example 2, f: manufacture example 3, g: manufacture example 4, h: manufacture example 5, i: manufacture example 6, j: comparative manufacture example 2),

Figure 5 is a graph showing the inhibitory effect on IL-8 in the inflammatory cytokines of Echochocho and elm tree mixture according to the present invention (a: positive control, b: negative control, c: Comparative Preparation Example 1, d: Preparation Example 1 , e: manufacture example 2, f: manufacture example 3, g: manufacture example 4, h: manufacture example 5, i: manufacture example 6, j: comparative manufacture example 2),

Figure 6 is a graph showing the inhibitory effect on TNF-α in inflammatory cytokines of Echochocho and Elm mixture according to the present invention (a: positive control, b: negative control, c: Comparative Preparation Example 1, d: Preparation Example 1 , e: manufacture example 2, f: manufacture example 3, g: manufacture example 4, h: manufacture example 5, i: manufacture example 6, j: comparative manufacture example 2).

Claims (17)

A pharmaceutical composition for preventing and treating allergic skin diseases, which contains a mixed extract of Eochocho extract and Elm extract as an active ingredient. The method of claim 1, wherein the Echochocho extract is a leaf, stem, root of Echochocho or a pharmaceutical composition for allergic skin disease prevention and treatment, characterized in that extracted by mixing two or more thereof. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 2, wherein the Echo-chocho extract is extracted from Echocho-cho leaves or leaves and stems. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 1, wherein the elm extract is extracted by selecting two or more leaves, stems, or roots of the elm. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 4, wherein the elm extract is extracted from the stem or stem and root of the elm tree. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 1, wherein the composition ratio of the Echo extract and Elm extract of the mixed extract is 9: 1 to 1: 9. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 6, wherein the mixing ratio of the Echo extract and Elm extract of the mixed extract is 8: 2-5: 5. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 6, wherein the mixing ratio of the Echo extract and Elm extract of the mixed extract is 7.5: 2.5 to 6.5: 3.5. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 1, wherein the Echo and Elm extracts are hot water extracts, alcohol extracts or organic solvent extracts. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 9, wherein the alcohol extract is methanol, ethanol or a mixed extract thereof. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 9, wherein the organic solvent extract is ethyl ether, chloroform, ethyl acetate, or a mixed extract thereof. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 1, wherein the mixed extract is sterilized by irradiation. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 1, wherein the composition inhibits a local skin inflammatory response. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 1, wherein the composition inhibits a systemic allergic reaction. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 1, wherein the composition inhibits secretion of inflammatory cytokines. The pharmaceutical composition for preventing and treating allergic skin diseases according to claim 1, wherein the allergic skin disease is selected from the group consisting of atopic dermatitis, psoriasis, contact allergic dermatitis and urticaria. A cosmetic composition for preventing and treating allergic skin diseases, comprising the mixed extract of any one of claims 1 to 16 as an active ingredient.

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