KR20110047064A - A composition comprising the extract of mixed herbs for preventing and treating atopic dermatitis - Google Patents

Abstract

PURPOSE: A composition containing complex herb extract is provides to suppress dermatitis and edema and to prevent and treat allergic diseases. CONSTITUTION: A pharmaceutical composition for preventing and treating allergic diseases contains complex herb extract of Lycium chinense Miller, Cuscuta japonica Chois., Rubus coreanus Miquel, and Schizandrae Fructus in a weight ratio of 1-24 : 7-21 : 5-15 : 1-3, as an active ingredient. The pharmaceutical composition further contains generally used proper carrier, excipient, and diluent. A health food for preventing and treating allergic diseases contains the complex herb extract as an active ingredient. The health food is manufactured in the form of powder, granule, capsule, tablet, or beverage.

Description

{A composition comprising the extract of mixed herbs for preventing and treating atopic dermatitis}

The present invention relates to a composition for the prevention and treatment of allergic diseases containing a complex herbal extract consisting of wolfberry, earth and sand, bokbunja and Schizandra as an active ingredient.

Document 1 Miller JS, et al., Curr. Opin. Immunol , 1 , pp.637-642, 1989

2 Christie and Henderson., Clin. Allergy Immunol, pp . 233-254, 2002

Nagai et al., J Pharmacol Exp Ther. 283 , pp. 321-327, 1997

4 Inagaki and Nagai., J Pharmacol Sci. 110 (3) , pp.251-259, 2009

[Reference 5] Choi, Byung-Hwi et al. 4, Allergy, 4 , pp.2-48, 2001

[Document 6] Korea Institute of Health Procedures, 2004

[7] Pokharel et al., Evid Based Complement Alternat Med . 5 . pp.173-180. 2008

Shore, PA et al., A method for the fluorometric assay of histamine in tissues. J. Pharmacol. Exp. Ther. 127 , p. 182, 1959

Due to environmental pollution, dietary habits and genetic causes, the number of patients with skin problems and skin diseases, including atopic and allergic diseases, is increasing continuously. In the United States, 5-12% of the population In Korea, there are about 2 to 3 million patients with skin diseases, but most of the steroid preparations that show serious side effects have not been developed. Rather, immunosuppressive agents are being developed. These preparations must be used with caution in clinical use because they involve side effects such as decreased immune function, atrophy of the skin, disruption of children, capillary expansion, acne, and corticosteroids.

Allergy refers to a hypersensitive reaction caused by contact with an innocuous antigen, an allergen, called an allergen, due to innate or acquired immune problems. The allergens that cause allergic reactions are called allergens. Typical allergens include pollen, drugs, vegetable fibers, bacteria, food, dyes, and chemicals. There are several defense mechanisms in the immune system to protect the body against antigens. The largest of these are lymphocytes, which are specialized for responding to specific antigens, such as B cells and T cells. B cells produce antibodies, which are proteins that bind to and destroy antigens and neutralize antigens. Instead of producing antibodies, T cells bind directly to the antigen and stimulate the attack. Allergic reactions manifest as immediate or delayed allergy, depending on whether the antigen reacts with either B- or T-cells.

Diseases include: anaphylaxis, allergic rhinitis, asthma, atopic dermatitis, contact dermatitis, seborrheic dermatitis, insect allergies, food allergies, drug allergies, and urticaria (Byung Hwi Choi et al. 4, Allergy, 4 , pp.2-48, 2001; Wuthrich B., Int. Arch.Allergy Appl.immunol. 90 , pp.3-10, 1989), and generally allergic diseases. In this case, it refers to the classic allergic disease in which atopic diseases are the main. Anaphylactic shock, allergic rhinitis, hay fever, bronchial asthma, drug allergies, plant allergies, urticaria, eczema, atopic dermatitis, allergic dermatitis, contact dermatitis, athlete's foot, psoriasis, psoriasis, herpes simplex / shingles , Dry skin, housewives and acne.

Allergy is involved in the interaction of several factors, such as genetic predisposition, environmental factors, pharmacological abnormalities, immunological factors, etc. The hypersensitivity reaction of the immune function of the living body is 4 It is divided into the types of branches. Type I hypersensitivity reaction occurs when IgE (immunoglobulin E), which is excessively produced by repeated exposure of allergens, binds to mast cells, and the histamine-containing granules are released. It causes systemic anaphylatic shock or local itching and inflammation. Representative diseases include atopic dermatitis and asthma.

Type II hypersensitivity reactions are caused by Null (K) cells, which destroy cells as the antibody binds to normal cells such as red blood cells, white blood cells, and platelets, causing hemocytopenia. Hemolytic anemia caused by cyclosporin anemia, leukopenia by aminopyrine, and thrombocytopenia by quinidine are typical. Type 3 hypersensitivity is a disease in which a polymorphonuclear (PMN) cell damages a tissue by depositing an antigen-antibody complex in the tissue, such as systemic lupus erythomatosis. On the other hand, type 4 hypersensitivity reactions are delayed type hypersensitivity reactions that cause sensitized T cells to differentiate into memory cells and subsequently cause dermatitis when resensitized, called contact dermatitis. In the sense, it belongs to the category of contact hypersensitivity (Miller JS, et al., Curr. Opin. Immunol , 1 , pp.637-642, 1989).

Among skin diseases, in particular, atopic dermatitis is a disease caused by an allergic reaction. The allergic reaction is divided into early specific immune response and late inflammatory response. Almost allergic reactions occur through mast cells and are activated through high-affinity IgE receptors (FcεRI) on the cell membrane. When the IgE antibody bound to the IgE receptor forms a bridge by the antigen, histamine and chondroitin sulfate stored in the granules through the action of phospholipase C, protein kinase C, and calcium ions. Heparin, protease and the like are released to mediate the initial stages of the reaction. Electrochemical carriers, including histamine, are the causative agents of various clinical symptoms seen early in the allergic reaction, with the largest amount being histamine. Therefore, the action by histamine in the allergic reaction is the main, the symptoms include vasodilation, edema. Prostaglandin and platelet-activating factor are also important chemical transporters in allergic reactions.Symptoms caused by the action of chemical transporters include dermatitis, pruritus, and skin redness. (Christie and Henderson., Clin. Allergy Immunol, pp. 233-254, 2002).

Contact dermatitis is a dermatitis caused by contact with foreign substances and is a kind of eczema. Contact dermatitis includes irritant contact dermatitis and allergic contact dermatitis, depending on the mechanism in which it occurs. A substance can cause these two reactions simultaneously.

Allergic contact dermatitis is a symptom that occurs when a person who is allergic (sensitized) to a 'specific' substance comes into contact with the causative agent, and only those who have come into contact with a particular substance are sensitized. The occurrence of dermatitis can be called allergic contact dermatitis. Such sensitization may occur with a single exposure, causing dermatitis, but symptoms usually occur after prolonged exposure to the skin for more than a few months. In general, sensitized people experience a skin reaction between 12 and 72 hours after re-exposure to the sensitized material. appear. It is often difficult to find the causative agent.

The substances that can cause allergic contact dermatitis are various such as various organic compounds, metals, lacquer and other plants, additives, cosmetics, fragrances, and synthetic resins contained in substances used around the life. Among the most common allergens are metals, the most common cause of allergic metals is nickel, and allergic contact dermatitis caused by nickel is present in 7-10% of the population. In addition, allergic contact dermatitis caused by dyes or rubbers is also common, and allergic contact dermatitis caused by lacquer trees is also common.

Another irritant of contact dermatitis Contact allergic dermatitis, unlike allergic contact dermatitis, is a dermatitis caused by a substance that causes dermatitis in all people when given a certain concentration of irritation. Can occur from. If the irritant is too irritating, one or two touches may cause chemical burns, red spots, swelling, and blisters on the skin, and the skin may be irritated repeatedly by weak irritants. Itchy and thickened dead skin cells. Therefore, the incidence is much higher than that of allergic contact dermatitis.

Causes of irritant contact dermatitis can be strong acids, strong alkalis, water detergents, chronically released oozes, diapers, and professionally used substances. The types of skin rashes caused by these causes include chemical burns caused by contact with strong acids or strong alkalis, housewives eczema, which is frequently caused by repeated long-term contact with water, detergents, soaps, etc. Irritant contact dermatitis includes diaper dermatitis caused by moisture and friction in the groin of children wearing diapers and occupational dermatitis caused by exposure to chemicals in various workplaces.

Contact dermatitis is classified into sun contact dermatitis, mercury contact dermatitis, or metal contact dermatitis depending on the contact material.

Plant-causing contact dermatitis includes warsi oil (extracted from mango), aloe, kiwi, celery and lemon, but it is most often caused by contact with lacquer after hiking in spring. Contact dermatitis caused by food is characterized by erythematous lesions accompanied by blisters at the contact site.

Metal contact dermatitis is often caused by the plating of watches, ornaments, etc. by elution by sweat, and is used as an antidote such as nickel chromium, a metal mixed with metal used for vulcanization of metal or rubber used as a material for textile dyes, or rubber. Organic mercury used, tameosal, kali dichromate used in leather operation, and the like.

DNCB (2,4-dinitrofluorobenzene) causes contact dermatitis, and repeated exposure of DNCB causes edema of the skin due to infiltration of inflammatory cells such as neutrophils, eosinophils, monocytes and epidermal abnormalities. In addition, DNFB is known to increase the concentration of IgE in the blood and has been widely used as an animal model for contact dermatitis by causing itching of the skin (Nagai et al., J Pharmacol Exp Ther. 283 , pp. 321-327, 1997 ; Inagaki and Nagai., J Pharmacol Sci. 110 (3) , pp.251-259, 2009)

When allergens are recognized by IgE, they are adhered to Langerhans cell surface IgE-attached Fc receptors, and T lymphocytes are activated by delivering antigens to T lymphocytes. In this case, T lymphocytes can also be activated by superantigens of autologous peptides or staphylococcus aureus . Unlike other skin diseases, inflammatory cells infiltrating skin lesions of atopic dermatitis are mainly Th2 cells, which produce cytokines such as IL-4 and IL-5, which promote blood IgE elevation and eosinophils, and cAMP force Abnormal monocytes of elevated atopic dermatitis with elevated phosphodiesterase increase PGE production, thereby inhibiting infiltration of Th1 lymphocytes. Th1 lymphocytes are also released from splenocytes that are readily activated in atopic dermatitis. It is also inhibited by the tumor necrosis factor (TNF). Eventually it inhibits Th1 proliferation in atopic dermatitis and leads to a decrease in cell mediated immunity. Various cytokines (cytokines) is to induce or increase the expression of various cell adhesion molecules to activate endothelial cells by promoting the return of the memory T-lymphocytes to cause the eczema lesions (choebyeonghwi et 4, allergic, 4, pp.2 -48, 2001).

In recent years, urban people are increasingly exposed to various allergens, such as mites living on carpets in their homes, dust that increases with humidity, pet hair, pollen, new fruits and food. As a result, asthma and atopic dermatitis, type 1 hypersensitivity, have increased in recent years and become a social problem, many researchers have been focused on the search for substances that can mitigate immune hypersensitivity from natural products. Similarly, in the case of skin application treatments, it is developed as a treatment for skin diseases by extracting the active ingredients of known anti-inflammatory or skin disease effects, but most of them only reduce the itch or inflammation and do not cure. Recently, medical skin care, which combines medical treatment and skin care, has been developed for skin treatment not only in Korea but also in the United States, Europe, and Japan, but it only improves the appearance of acne, blemishes, and freckles. The effect is not clear for allergic skin diseases, diseases caused by reduced immune function and aging.

In addition, the exploration of new functional substances from natural products is accelerating with the establishment of the Korea Food and Drug Administration's notification on the evaluation of the efficacy and safety of functional foods and functional cosmetics and the approval procedure (Korean Health Procedures Research Association, 2004). Reflecting these social phenomena, the development of more effective new drugs through the scientification of natural products in a highly industrialized society is recognized as an important factor in securing national competitiveness. Food sweeteners, flavorings, health functional foods, functional cosmetics, natural pesticides, etc. have been developed in various ways, but the systematic research is still insufficient.

The wolfberry is called 枸杞 (Goji) because the thorns are similar to the bark tree (formerly 枸) and the stem is similar to the willow tree (Gi:,). Fruits of other plants of the same genus are used. Tinnitus, Western, Kigi, Gugi, Gugye, Gugeuk, and Meat. ), Ceiling, Jigol, Jibo, Jiseon, Memorandum, Yangyu, Cactus, or West Wang Mojang It is called. In China, the Nyja is used by Cyclone barbarum L .: 寧 夏 拘 杞子, and in Japan, it is Lycium chinense Miller and Lycium barbarum L .: 寧 夏 拘 杞子. It is characterized by almost no smell, astringent, and slightly weak and cold. Pharmacological action, non-specific immune boosting effect, hematopoietic effect, cholesterol lowering effect, anti-fatty liver action, blood pressure lowering, hypoglycemic effect, growth promoting or anti-cancer effect.

Cuscuta japonica Chois. Is a seed of the annual ginseng, a vine plant belonging to the Coniferous family, also called bird ginseng seed. The new ginseng is a parasitic or wormwood that absorbs nutrients, so there is no root in the ground, no chlorophyll in the whole, and yellow or yellow chestnut vines grow by winding up other plants. Taste is very sweet and has a very flat nature. It is known as a medicine that mainly protects the liver and kidneys, brightens the eyes, helps Yang, and strengthens the kidney function. Impotence, spontaneously flowing semen or mungjeong (夢 精) is effective.

Bokbun is a medicinal herb (Rubus coreanus Miquel) made from unripe fruits (Korea and China). The name Bokbunja is derived from the folk tales that the urine stalks are inverted when the fruit is eaten, and the name Bokbunja is called `` Bok, Yo-gang, and Ai-za ''. As other names, Kwanbunja, Bokbun, Oh Pyoja, Daemakmae, Seopjeon Pyo, Disaster Mark, Seogukcho It is also called Philunga (畢 楞伽), Gyu (), or Consolidation (). This drug is odorless, tastes sweet and sweet. Bokbunja is mentioned in various ancient literatures such as Dongbobom, Dangwon-myeoncho, Herbaceous greenery, and even in modern medicine pharmacological analysis, it contains a large amount of polyphenols in the fruit. Or has a bactericidal effect.

Schisandra chinensis is a fruit of Schisandra chinensis, dark red with a diameter of about 1cm, ball-shaped, about 1cm in diameter, and dark red. It has five flavors: sweet, sour, bitter, salty, and spicy, with the strongest of them. Schizandra chinensis includes Schisandra chinensis (North Schisandra chinensis), South Schisandra chinensis or Black Schisandra chinensis, mainly grown in Taebaeksan area, South Schisandra grows in southern island region, and Schisandra chinensis grows in Jeju Island, and is produced in Korea, Japan, Sakhalin Island, China, etc. do. It contains ingredients such as xanthrin, gomisin, citric acid, malic acid, citric acid, etc. It is used as a tonic by strengthening the heart, lowering blood pressure, and increasing immunity. It works.

Therefore, the present inventors have shown that the WH-001 extract composed of wolfberry, earth and sand, bokbunja and Schizandra chinensis showed the inhibitory effect of dermatitis and edema in animal models of contact dermatitis allergic disease caused by DNFB and affected the production of IgE, the main antibody of allergic reaction. In addition to inhibiting in the tissue, by confirming the inhibitory effect on histamine release from mast cells, the anti-allergic effect was confirmed to complete the present invention.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of allergic diseases containing a complex herbal extract consisting of wolfberry, earth and sand, bokbunja and Schisandra chinensis as an active ingredient.

In another aspect, the present invention provides a health functional food for the prevention and improvement of allergic diseases containing a complex herbal extract consisting of wolfberry, earth and sand, bokbunja and Schisandra chinensis as an active ingredient.

In addition, the present invention provides an oral administration skin protector and skin disease improving agent containing a complex herbal extract consisting of goji, earth and sand, bokbunja and Schisandra chinensis having an allergic effect as an active ingredient.

In addition, the present invention provides a skin protective agent and skin disease improving agent containing a complex herbal extract consisting of goji berry, earth and sand, bokbunja and Schisandra chinensis having an allergic disease effect as an active ingredient.

Complex herbal extracts defined herein have a weight ratio of 1 to 24: 7 to 21: 5 to 15: 1 to 3, preferably 5 to 10: 5 to 10: 2 to 7: The mixture mixed at the weight ratio of 1-3.

The extract as defined herein is an extract available in a solvent selected from water, a lower alcohol of C ₁ to C ₄ or a mixed solvent thereof, preferably an extract available in water, ethanol, methanol, butanol or a mixed solvent thereof. More preferably, an extract soluble in water.

Allergic diseases as defined herein include athlete's foot, blemishes, psoriasis, herpes simplex / herpes zoster, dry skin, housewives, acne, hypersensitivity, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, atopic dermatitis, contact dermatitis , Urticaria, insect allergy, food allergy or drug allergy, preferably allergic rhinitis, asthma, allergic dermatitis, atopic dermatitis, contact dermatitis, urticaria, food allergy or drug allergy, more preferably atopic dermatitis or Contact dermatitis.

Hereinafter, a method of obtaining the complex herbal extract of the present invention will be described in detail.

Complex herbal extract of the present invention can be prepared by the following manufacturing process.

For example, dried wolfberry, earthenware, bokbunja and schizandra are in a suitable ratio, preferably 1 to 24: 7 to 21: 5 to 15: 1 to 3, and preferably 5 to 10: 5 to 10: 2 ˜7: 1, mixed in a weight ratio of 1 to 3, soluble in a solvent selected from 1 to 20 times the dry weight, preferably 5 to 15 times the volume of water, C ₁ to C ₄ lower alcohol or a mixed solvent thereof. Extract, preferably an extract available in water, ethanol, methanol, butanol or a mixed solvent thereof, more preferably 70 to 150 ° C. for 1 to 10 hours, preferably 2 to 5 hours, preferably with water The extraction method, such as cold extraction, hot water extraction, heating extraction, ultrasonic extraction and reflux cooling extraction to 90 ℃ to 110 ℃, preferably after hot water extraction, the extract is filtered and concentrated under reduced pressure and dried through the manufacturing process of the present invention Complex herbal extracts can be obtained.

The present invention provides a pharmaceutical composition for the prevention and treatment of allergic diseases containing the complex herbal extract obtained by the above method as an active ingredient.

The pharmaceutical composition for the prevention and treatment of allergic diseases containing the complex herbal extract of the present invention comprises 0.1 to 50% by weight of the complex herbal extract 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 pharmaceutical composition containing the complex herbal extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions.

The pharmaceutical composition containing the herbal extract according to the present invention may be prepared in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. It can be formulated and used in the form. Carriers, excipients and diluents that may be included in the composition containing the complex herbal extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, Acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil Can be mentioned. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose in the extract. Mixed with gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The amount of the complex herbal extract of the present invention may vary depending on the age, sex, and weight of the patient, but may be 0.1 to 100 mg / kg, preferably 1 to 10 mg / kg once or several times daily. The dosage may also be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like. Accordingly, the dosage is not limited in any way to the scope of the present invention.

The pharmaceutical composition may be administered to various mammals such as mice, mice, livestock, humans, and the like. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections.

The present invention provides a dietary supplement for the prevention and improvement of allergic diseases containing complex herbal extract as an active ingredient.

Foods to which it may be added include various foods, powders, granules, tablets, capsules, syrups, beverages, gums, tea vitamin complexes, and health functional foods.

The complex herbal extract itself of the present invention is a drug that can be used with confidence even when taken for a long time for the purpose of prevention because there is little toxicity and side effects.

Complex herbal extract of the present invention may be added to food or beverage for the purpose of preventing and improving allergic diseases. At this time, the amount of the composite herbal extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health functional beverage composition is added in a ratio of 0.02 to 10g, preferably 0.3 to 1g based on 100ml Can be.

The health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the complex herbal extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Can be. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above, the herbal extract of the present invention may be used in various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, such as flavoring agents, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the complex herbal extract of the present invention may contain a pulp for the production of natural fruit juices and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the complex herbal extract of the present invention.

As described above, the complex herbal extract consisting of wolfberry, earth and sand, bokbunja and Schisandra chinensis shows the inhibitory effect of dermatitis and edema in animal models of contact dermatitis allergic disease induced by DNFB, and suppresses the production of IgE, the main antibody of allergic reaction. In addition to inhibiting in the affected tissues, and showing an inhibitory effect on histamine release from mast cells, it can be usefully used as a pharmaceutical composition and health functional food for the prevention and treatment of allergic diseases.

Below, The invention is illustrated in detail by the following examples and experimental examples.

However, the following Examples and Experimental Examples are only illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Example 1 Preparation of Goji Extract

100 g of wolfberry purchased from Gyeongdong market was extracted with 1.5 L of distilled water at 100 ° C. for 3 hours, and then filtered through a filter paper. The solvent was distilled off and the remaining residue was vacuum filtered to obtain a filtrate. The filtrate was concentrated under reduced pressure (EYELA, N-1000, Japan) and lyophilized to obtain 10g of Goji berry extract was used as a sample of the following experimental example.

Example 2. Preparation of Tosa Extract

After extracting 100 g of the earthenware purchased from Gyeongdong market with 1.5 L of distilled water at 100 ° C. for 3 hours, the filtrate was filtered and the remaining residue was distilled off under vacuum to obtain a filtrate. The filtrate was concentrated under reduced pressure (EYELA, N-1000, Japan) and lyophilized to obtain 10 g of Tosa extract, which was used as a sample of the following experimental example.

Example 3. Preparation of Bokbunja Extract

After extracting 100 g of bokbunja purchased from Gyeongdong market with 1.5 L of distilled water at 100 ° C. for 3 hours, filtering with a filter paper, and then distilling the solvent off, the residue was vacuum filtered to obtain a filtrate. The filtrate was concentrated under reduced pressure (EYELA, N-1000, Japan) and lyophilized to obtain 10 g of bokbunja extract was used as a sample of the following experimental example.

Example 4. Preparation of Schizandra chinensis Extract

After extracting 100 g of Schizandra chinensis from Gyeongdong market with 100 liters of distilled water at 100 ° C. for 3 hours, the mixture was filtered through a filter paper, the solvent was distilled off, and the residue was vacuum filtered to obtain a filtrate. The filtrate was concentrated under reduced pressure (EYELA, N-1000, Japan) and lyophilized to obtain 10 g of Schisandra chinensis extract, which was used as a sample of the following experimental example.

Example 5. Preparation of Complex Herbal Extract

68 g of Gojija, 56 g of Tosa, 40 g of Bokbunja and 8 g of Schisandra chinensis were purchased from Kyungdong Market, and extracted with 2 L of distilled water at 100 ° C. for 3 hours. After filtration with a filter paper, the solvent was distilled off and the remaining residue was vacuum filtered to obtain a filtrate. The filtrate was concentrated under reduced pressure (EYELA, N-1000, Japan) and lyophilized to obtain 17 g of a composite herbal extract (hereinafter referred to as “WH-001”), which was used as a sample in the following experimental example.

Reference Example 1. Preparation of Laboratory Animals

Five-week-old Balb / c mice were supplied from the Central Experimental Animal Co., Ltd. and used after undergoing laboratory purification for about one week. Six mice were housed in a cage for mice (220 × 200 × 145 mm). The environment of the animal laboratory was controlled at a temperature of 21-25 ° C., a relative humidity of 45-65%, a frequency of 12 ventilations / hour, a lighting cycle of 12 hours, and an illuminance of 150-300 lux. Purina Rat Chow ^® , a pellet-type solid feed for laboratory animals, is available from Nestle Purina PetCare Korea Ltd. It was supplied from (Seoul, Korea) and fed, and the negative water was allowed to take sterile purified water freely.

Reference Example 2. Induction test and sample treatment of allergic dermatitis

Balb / c mouse of Reference Example 1 using a depilatory agent (sensitive skin veet), and epilatate the back area and after 24 hours diluted DNFB (2,4-dinitrofluorobenzene) to 0.15% in acetone (aceton) 100 ul was applied to the back of the mouse and the right ear, and 50 ul was applied one week later, and then twice a week was repeated to induce dermatitis. After 3 weeks, the dermatitis-induced mice were divided into 4 groups, and the acetone-coated group and the DNFB-coated group were treated with distilled water, and then divided into 0.01 mg / g WH-001 and 1 mg / g WH-001 groups. WH-001) was orally administered at 0.01 mg / g and 1 mg / g, respectively, and acetone and DNFB were applied. One week later, fasting for 24 hours before the experiment, the blood was collected from the heart after the abdomen in light ether anesthesia and centrifuged (3,000 g, 10 minutes) to obtain a serum, and stored at -70 ℃ until the experiment proceeds.

Reference Example 3. Statistical Analysis

Each experimental results SPSS statistical analysis program (version 11.0) for use by was to calculate the average and standard deviation (SD), confirmed the homogeneity of the dispersion by Levene's test, and under significant difference of 5% and subjected to T-test (p <0.05) was determined to have statistical significance.

Experimental Example 1. Inhibition of dermatitis and edema of complex herbal extract (WH-001)

Balb / c mice prepared in Reference Example 2 after 4 weeks to determine the skin damage (clinical score) of the mouse. Skin damage is good for erythema and hemorrhage, edema and excoriation, erosion and scarring (0), weak (1), severe (2), very It was evaluated as severe (3), and the evaluation scores were summed and averaged for each experimental group, and visual evaluation was conducted by a general observer who was not involved in the experiment.

In addition, the degree of edema of the right ear was measured using a micrometer (Absolute digimatic, Mitutoyo).

As a result, as shown in FIG. 1, in the DNFB treatment group, the skin became red and rough from the 2nd week of DNFB application, and in severe cases, symptoms of severe dermatitis such as bleeding started, and the DNFB treatment site was noticeably thicker than the non-skin. On the contrary, the experimental group to which WH-001 was administered was able to noticeably improve the symptoms of dermatitis (see FIG. 1).

As a result of measuring the clinical score of each mouse based on the above experimental results, as shown in FIG. 2, the skin damage was 4.42 in the DNFB treatment group, whereas the concentration of 0.01 mg / g of WH-001 was observed. 3.5 and a score of 4.16 at 1 mg / g concentration. Although the clinically favorable scores were obtained in the drug treatment group compared to the DNFB alone treatment group, statistical significance could not be observed (see FIG. 2).

In addition, as a result of measuring the ear edema inhibitory effect of WH-001 in the DNFB-induced animal model, it can be seen that the ear edema of the DNFB-treated group increased twice as much as the acetone-treated ear as shown in FIG. , WH-001 administration group showed a slight decrease in edema of the ear compared to DNFB treatment group, but statistical significance could not be observed (see FIG. 3).

Experimental Example 2. Measurement of serum Immunoglibulin E inhibitory effect

In order to determine the allergic reaction inhibitory effect by the composite herbal extract (WH-001) obtained in Example 5, the experiment was performed as follows according to the literature (Pokharel et al., Evid Based Complement Alternat Med . 5 . pp.173-180. 2008) .

In order to induce dermatitis in Balb / c mice, the hair was removed, and then serum was collected by applying DNFB to observe changes in IgE, a mediator of the inflammatory response.

Each sample obtained from the blood obtained by the method of Reference Example 2 was measured using an immunoenzyme assay (Mouse IgE ELISA KIT, Pharmingen, USA). 100 ul of the sample was placed in an anti-mouse IgE microwell strip plate, left for 1 hour, and washed four times. In addition, each anti-mouse IgE-HRP conjugate was put in 100ul, and left for 30 minutes and washed five times. 100 ul TMB substrate was placed in each well and photosensitive for 15 minutes, then 100 ul of stop solution was added and measured by ELISA (VersaMax ™ Microplate Reader, Molecular Devices, USA) 405 nm.

As a result, as shown in Figure 4 DNFB treated group significantly increased the amount of IgE compared to acetone treated group, while Wg-001 extract treated group measured IgE at a concentration substantially similar to or lower than that of acetone treated group, WH-001 extract was found to have an anti-allergic effect (see Figure 4).

Experimental Example 3 Measurement of Inhibition of Histamine Release from Mast Cells

In order to confirm the inhibitory effect on the histamine release from mast cells of the complex herbal extract (WH-001) obtained in Example 5, the experiment described in the literature was applied as follows (Shore, PA et al., A method for the fluorometric assay of histamine in tissues.J. Pharmacol.Exp. Ther. 127 , p . 182, 1959).

To examine the free inhibitory effect of WH-001 on RPMCs cells, which are intraperitoneal mast cells of SD rats, WH-001 was treated by concentration on the RPMCs cells (2 × 10 ⁵ cells / ml) incubated at 37 ° C. After 30 minutes, the mixture was released using compound 48/80 (6 µg / mL), and the histamine released for 15 minutes was quantified and observed.

That is, 500 μl of the sample was taken in an Eppendorf tube, and 450 μl of 0.1 M HCl and 50 μl of a 60% perchloric acid solution were mixed, followed by centrifugation (400 g , 20 minutes, 5415 R, Eppendorf). 800 μl of the supernatant was taken and placed in a test tube containing 500 μl of 5 M NaOH solution, 3 ml of distilled water, 10 ml of n-butanol, and 1.2 g of NaCl, followed by shaking, followed by centrifugation (500 g , 10 minutes). Take 8 ml of butanol layer from the test tube, add 3 ml of 0.1 M HCl and 10 ml of n-heptane, shake and centrifuge again (500 g , 10 minutes) to 400 ml of 1 M NaOH in 2 ml of aqueous layer, 100 μl of a 1% o-phthaldialdehyde solution (Sigma, Cat No. P1378) was added to the mixture, allowed to stand for 2 minutes, and the fluorescence intensity was measured at an emission wavelength of 438 nm and an excitation of 353 nm. Measurement was performed using RF-5301 PC, Shimadzu Co., Ltd.).

As shown in FIG. 5, it was confirmed that WH-001 inhibited the release of histamine by 20% at 1 mg / ml by compound 48/80 in mast cells, and statistically significant differences were observed. (See FIG. 5).

It describes a formulation example of a composition comprising a composite herbal extract of the present invention (WH-001), the present invention is not intended to limit it, but is intended to explain in detail only.

Formulation Example 1 Preparation of Powder

Complex Herbal Extract (WH-001) 20 mg

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

Complex herbal extract (WH-001) 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation Example 3 Preparation of Capsule

Complex herbal extract (WH-001) 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

Complex herbal extract (WH-001) 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _4, 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation Example 5 Preparation of Liquid

Complex Herbal Extract (WH-001) 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding lemon flavor appropriately, mixing the above components, adding purified water, adjusting the whole to 100 ml by adding purified water, and then filling into a brown bottle. The solution is prepared by sterilization.

Formulation Example 6 Preparation of Healthy Food

Complex herbal extract (WH-001) 1000 mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health functional food in a preferred embodiment, the composition ratio may be arbitrarily modified, and the above components may be mixed according to a conventional health food manufacturing method. Next, the granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation Example 7 Preparation of Healthy Drink

Complex herbal extract (WH-001) 1000 mg

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

After mixing the above components according to the conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored Used to prepare the healthy beverage composition of the invention.

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

1 is a diagram showing the skin improvement effect of the composite herbal extract (WH-001) in the animal model induced by DNFB,

2 is a diagram showing the skin improvement effect of the composite herbal extract (WH-001) in the DNFB-induced animal model,

Figure 3 is a diagram showing the inhibitory effect of IgE in the blood of the animal model administered the complex herbal extract (WH-001) (* P <0.05-significantly different from blank group (p = 0.035); #p <0.02-significantly different from control group (p = 0.012)),

4 is a diagram showing the effect of inhibiting ear edema of the complex herbal extract (WH-001) in the animal model induced by DNFB,

5 is a diagram showing the histamine release effect by the compound 48/80 in PBMCs administered with the composite herbal extract (WH-001) (* P <0.05; significantly different from the control group).

Claims (9)

A pharmaceutical composition for the prevention and treatment of allergic diseases, comprising as an active ingredient a complex herbal extract consisting of wolfberry, earth and sand, bokbunja and Schisandra chinensis. The pharmaceutical composition of claim 1, wherein the complex herbal extract has a weight ratio of 1 to 24: 7 to 21: 5 to 15: 1 to 3, respectively. The pharmaceutical composition according to claim 1, wherein the extract is an extract available in a solvent selected from water, C ₁ to C ₄ lower alcohols, or a mixed solvent thereof. The method of claim 1, wherein the allergic disease includes athlete's foot, scab, psoriasis, herpes simplex / herpes zoster, dry skin, housewives, acne, hypersensitivity, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, atopic dermatitis, A pharmaceutical composition comprising contact dermatitis, urticaria, insect allergy, food allergy or drug allergy. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises a suitable carrier, excipient and diluent commonly used in the manufacture of pharmaceutical compositions. A health functional food for the prevention and improvement of allergic diseases containing a complex herbal extract consisting of gojija, earth and sand, bokbunja and Schisandra chinensis as an active ingredient. 7. The dietary supplement of claim 6 which is a powder, granule, tablet, capsule or beverage. A skin protector for oral administration and a skin disease improving agent containing a complex herbal extract consisting of goji, earth and sand, bokbunja and schisandra chinensis having an allergic disease effect as an active ingredient. Skin protective agent and skin disease improving agent containing a complex herbal extract consisting of gojija, earth and sand, bokbunja and Schisandra chinensis having an allergic disease effect as an active ingredient.

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