KR101842786B1 - A composition for treating atopic dermatitis comprising the extract of herbal mixture - Google Patents

Abstract

The present invention relates to a composition for the treatment of atopic dermatitis comprising a crude drug mixture extract, and more particularly to a pharmaceutical composition for preventing or treating atopic dermatitis comprising a mixed extract of yellow, white, Food compositions, quasi-drug compositions, cosmetic compositions, and methods of treating atopic dermatitis using the pharmaceutical compositions.

Description

[0001] The present invention relates to a composition for treating atopic dermatitis,

The present invention relates to a composition for the treatment of atopic dermatitis comprising a crude drug mixture extract, and more particularly to a pharmaceutical composition for preventing or treating atopic dermatitis comprising a mixed extract of yellow, white, Food compositions, quasi-drug compositions, cosmetic compositions, and methods of treating atopic dermatitis using the pharmaceutical compositions.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease, often caused by allergic diseases such as food allergy, asthma or rhinitis. AD is characterized by an increase in the number of eosinophils, an increase in serum IgE levels, and an increase in proinflammatory cytokines, including TNF-α and chemokines (Simon D. et al., 2004, 59, 561 -570; Rousset F. et al., J Allergy Clin Immunol., 1991, 87, 58-69). The IgE induces mast cell activation whereby immunomodulators, including histamine precursors, chemokines and cytokines, are released from mast cells. These cytokines promote the Th2-subtype T cell response observed in skin lesions at the acute phase of AD, and the combination of these Th2 and Th1 responses modulates the immune response during the chronic phase of AD.

Local corticosteroids have been used as standard therapies for acute AD, but have been reported to cause adverse effects on skin genes (Lubach D. et al., Dermatologica, 1989, 179, 67-72) , It is necessary to develop a safe anti-inflammatory factor even if it is used for a long time without steroids. In this regard, tacrolimus, a topical immunosuppressant, is currently being used to treat AD. Since tacrolimus has a relatively small molecular size and penetrates effectively into the skin, it has been used in the form of topical ointment preparations (Akhavan A. et al., Semin Cutan Med Surg., 2008, 27, 151-155). It does not cause collagen synthesis or sclerosis, which is a kind of side effect caused by corticosteroids, and can be safely used in areas where skin is thin and very fragile, such as face or neck. However, as long as tacrolimus is used for a long time, the effect is halved and side effects may occur. Therefore, development of new medicines for treating AD is required.

Accordingly, the development of a therapeutic agent for atopic dermatitis using natural products has been actively carried out, and a composition for improving atopic dermatitis including a fermented ginseng or a red ginseng extract having enhanced ginsenoside Rd (Korea Patent Publication No. 2016-0019190) (Korean Patent Laid-Open Publication No. 2015-0065250), a composition for improving atopic dermatitis containing a mung bean extract (Korea Patent Publication No. 2014-0063165), and the like have been developed.

On the other hand, yellowish (Cortex Phellodendri), mold opening (Schizonepetae Spica , Sophorae Radix , Glycyrrhizae Radix or Liriopis Tuber are medicinal herbs used in oriental medicine. They are used for menopause, liver, digestion, antibacterial, uterine bleeding, menstrual disorders, dysentery, And the like. However, no combination thereof has been used as a medicament, and the effect of the above combination on atopic dermatitis has not been known.

Under these circumstances, the inventors of the present invention have made intensive efforts to develop a therapeutic agent for atopic dermatitis using natural products, and as a result, it has been confirmed that a mixed extract of Hwangbaek, Chungsu, Gosam, Licorice and Makkumongdong can treat atopic dermatitis by inhibiting the immune response , Thereby completing the present invention.

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating atopic dermatitis, which comprises a mixed extract of Hwangbuk, Brocoli, Gossam, Licorice, and Macmundan or a fraction thereof.

Another object of the present invention is to provide a method for treating atopic dermatitis comprising the step of administering the pharmaceutical composition to a suspected individual having atopic dermatitis other than human.

It is another object of the present invention to provide a food composition for improving atopic dermatitis, which comprises a mixed extract of yellow whites, red ginseng, ginseng, licorice, and ginseng root, or a fraction thereof.

It is another object of the present invention to provide a quasi-drug composition for prevention or improvement of atopic dermatitis, which comprises a mixed extract of Hwangbaek, Kyeonggi, Gosam, Licorice, and Macmundan or a fraction thereof.

It is another object of the present invention to provide a quasi-drug composition for prevention or improvement of atopic dermatitis, which comprises a mixed extract of Hwangbaek, Kyeonggi, Gosam, Licorice, and Macmundan or a fraction thereof.

One aspect for achieving the above object is to provide a pharmaceutical composition for preventing or treating atopic dermatitis, which comprises a mixed extract of yellow whites, red ginseng, ginseng, licorice, and ginseng root or fractions thereof.

In the present invention, it was confirmed that the mixed extracts of yellow whites, molds, gossam, licorice and marshmallow effectively reduce the symptoms of atopic dermatitis, so that the extract can be used as a treatment for atopic dermatitis. It has not been previously known that the combination of yellow, white, red, ginseng, licorice, and macromuscularids has a therapeutic effect on atopic dermatitis and was first identified by the present inventors.

The term "yellowish" (黃柏) of the present invention to provide a medicine dried bark of Phellodendron amurense, saengyakmyeong Phellodendri Cortex, scientific name Phellodendron wilsonii . It is said to be used for nerves, bladder, colonoscopy, and sympathies.

The term "japanese" of the present invention refers to a dried apricot which is a plant of the family Lamiaceae and a plant of the genus Schizonepetae Spica , Scientific name Schizonepeta tenuifolia . It is characterized by the fact that it is warm and has a characteristic taste. It is known to exhibit digestion, antibacterial action, and the like, acting on menopause, liver, and the like.

The term "Sophora" (苦蔘) of the present invention is stripped of the roots of Sophora jupi, saengyakmyeong Sophorae Radix, scientific name Sophora flavescens . It has a peculiar odor and persistence. It is characterized by its extremely soft and cold taste. It is said to be used when it is used for dysentery, fever, dullness, skin itching due to wet heat, and pain due to bladder fever.

The term, "liquorice" (甘草) of the present invention is the dried root or stem of licorice, saengyakmyeong Glycyrrhizae Radix, scientific name Glycyrrhiza glabra . It has a characteristic odor and taste is sweet. Licorice is known to harmonize the toxicity of all medicines, to make medicinal effects appear better, to control the heat and scent of the books, to communicate all blood vessels, and to strengthen muscles and bones.

In the present invention, the mixed extract of Phellodendron, Chrysanthemum, Gossam, Licorice, and Macromuscular can be named in combination with "KAJA" or "KHU-ATO-JIN-A". The above-mentioned mixed extract may be an extract of a mixture of yellow, white, red ginseng, licorice, and ginseng, and may also be a mixture of yellowish white, red ginseng, licorice, or ginseng extract.

In the present invention, the above-mentioned yellow, white, red ginseng, licorice and licorice can be commercially purchased, used, or harvested or cultivated, but the present invention is not limited thereto.

The extract of the present invention may be obtained by extracting a mixture of yellow, white, red ginseng, licorice, and ginseng root with at least one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof.

The term "extract " of the present invention means an extract obtained by extracting a mixture of yellowish white, red ginseng, ginseng, licorice, and ginseng root, a diluted solution or concentrate of the extract, a dried product obtained by drying the extract, Water, or a mixture thereof, and extracts of all the formulations that can be formed using the extract.

In the present invention, the method for extracting the mixture is not particularly limited, and the extract may be extracted according to a method commonly used in the art in the mixed extracts of yellow whites, molds, ginseng, licorice and licorice. Non-limiting examples of the extraction method include hydrothermal extraction, ultrasonic extraction, filtration, and reflux extraction. These may be performed alone or in combination with two or more methods.

The kind of the extraction solvent used for extracting the mixture in the present invention is not particularly limited, and any solvent known in the art can be used. The extraction solvent may be, for example, water, alcohol, or a mixed solvent thereof. These solvents may be used alone or in admixture of one or more, and specifically, water may be used. When an alcohol is used as a solvent, an alcohol having 1 to 4 carbon atoms can be specifically used.

The term "fraction " of the present invention means a product obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.

The fractionation method for obtaining the fraction in the present invention is not particularly limited and may be carried out according to a method commonly used in the art. Non-limiting examples of the fractionation method include a solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed through an ultrafiltration membrane having a constant molecular weight cut-off value, various chromatography (size, charge, hydrophobicity Or affinity-based separation), and a combination thereof, and the like. Specifically, the extract of the maple leaf of the present invention is treated with a predetermined solvent to obtain a fraction from the extract.

The kind of the fraction solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the fraction solvent include polar solvents such as water and alcohols having 1 to 4 carbon atoms; Non-polar solvents such as hexane, ethyl acetate, chloroform and dichloromethane; Or a mixed solvent thereof. These may be used alone or in combination of one or more, but the present invention is not limited thereto.

In addition, the extract or fraction may be prepared and used in the form of a dry powder after extraction, but is not limited thereto.

In the present invention, the mixture of yellowish white, red ginseng, red ginseng, licorice ginseng and ginseng roots is selected from the group consisting of yellowish white, red ginseng, red ginseng, licorice ginseng and ginseng root at a weight ratio of 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5 But is not limited to, a weight ratio of 0.7: 1.3 to 0.7: 1.3: 0.7 to 1.3: 0.7 to 1.3: 0.7: 1.3, more specifically, a weight ratio of 1: 1: 1: 1:

The term "atopic dermatitis" (AD) of the present invention is a kind of autoimmune skin disease, and is a disease accompanied by skin swelling, eczema, and tickling. It is known that both environmental and genetic factors are involved in the onset of the atopy, but the mechanism of the exact pathogenesis has not been elucidated. In the present invention, the atopic dermatitis can be named in combination with "AD ".

The term "prevention" of the present invention means any action that inhibits or delays atopic dermatitis upon administration of a composition comprising the extract.

The term "treatment" of the present invention means all the actions of improving or alleviating symptoms of atopic dermatitis by the administration of the composition containing the extract.

In one specific embodiment of the present invention, the mixed extracts of Hwangbaek, Brocoli, Gossam, Licorice, and Macmundan according to the present invention are excellent in improving the clinical symptoms of atopic dermatitis such as erythema / hemorrhage, edema, dry / dry, abrasion / (Fig. 4); Inhibit infiltration of inflammatory cells or mast cells into the epidermis and dermis (Figures 5 and 6); Reducing the number of white blood cells (Fig. 8); And decreased levels of inflammatory cytokines IL-6, IL-10 and IL-12, including serum IgE (FIGS. 9 and 10). This suggests that the extract can be useful for prevention or treatment of atopic dermatitis.

The pharmaceutical composition of the present invention may include, but is not limited to, 0.001 to 80, specifically 0.001 to 70, more specifically 0.001 to 60% by weight of the extract, based on the total weight of the composition.

In addition, the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier, excipient or diluent conventionally used in the manufacture of a pharmaceutical composition, wherein the carrier comprises a non-naturally occuring carrier . Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The pharmaceutical compositions may be formulated into tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, nonaqueous solutions, suspensions, emulsions, It can be formulated in the form of a percutaneous absorbent, a gel, a lotion, an ointment, a cream, a patch, a cataplasma, a paste, a spray, a skin emulsion, a skin suspension, a transdermal patch, a drug containing bandage or suppository . Specifically, when formulating, it can be prepared by using diluents or excipients such as fillers, weights, binders, humectants, disintegrants, surfactants and the like commonly used. Solid formulations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, and the like. Such a solid preparation may be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration, liquid paraffin, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of the suppository base include withexol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

Another embodiment provides a method for treating atopic dermatitis comprising administering the pharmaceutical composition to a suspected individual having atopic dermatitis other than human.

The term "administering" of the present invention means introducing a composition comprising said extract into a subject in an appropriate manner.

The term "individual" of the present invention means all animals such as mice, mice, livestock, and the like, including humans who have developed or are capable of developing atopic dermatitis. As a specific example, it may be a mammal including a human.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the species and severity, age, sex, The sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. For example, the combined extracts of yellow, white, red ginseng, licorice, and ginseng can be administered at a dose of 0.01 to 500 mg / kg per day, specifically 10 to 100 mg / kg, It may be administered once or several times.

The pharmaceutical composition may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art.

In addition, the pharmaceutical composition may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may be determined depending on the condition and the weight of the patient, The mode of administration, the route of administration, and the time, but may be appropriately selected by those skilled in the art.

Another embodiment provides a food composition for improving atopic dermatitis, which comprises a mixed extract of yellow, white, red, ginseng, licorice, and marshmallow, or a fraction thereof.

At this time, the definitions of the above-mentioned yellowish white, hungfu, gosam, licorice, ginseng, extract, fraction and atopic dermatitis are as described above.

The term "improvement" of the present invention means all actions that at least reduce the degree of symptom associated with the condition to be treated by administering the composition comprising the extract.

The term "food" of the present invention includes dairy products such as meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen and other noodles, gums, ice cream, various soups, drinks, tea, , A vitamin complex, a health functional food, and a health food, all of which include foods in a conventional sense.

Since the food composition of the present invention can be ingested routinely, it can be expected to be highly effective for improving atopic dermatitis, and thus can be very useful for health promotion purposes.

The term "functional food" as used herein means the same term as "food for special health use" (FoSHU). In addition to nutrition, It means food. Here, 'function (surname)' refers to the structure and function of the human body to obtain a beneficial effect for health use such as controlling nutrients or physiological action. The food of the present invention can be prepared by a method commonly used in the art and can be prepared by adding raw materials and ingredients which are conventionally added in the art. In addition, the above-mentioned food formulations can be manufactured without limitations as long as they are formulations recognized as food. The composition for food of the present invention can be manufactured in various formulations, and unlike ordinary drugs, it has advantages of being free from side effects that may occur when a natural product is used as a raw material for a long period of time, and is excellent in portability. The food of the invention can be ingested as an adjuvant to improve the atopic dermatitis improving effect.

The health food refers to a food having an active health promotion or promotion effect compared with a general food, and a health supplement food refers to a food for health assistance. In some cases, the terms health functional foods, health foods, and health supplements are used.

Specifically, the health functional food is a food prepared by adding the compound of the present invention to a food material such as a beverage, a tea, a spice, a gum, confectionery, or the like, or encapsulated, powdered or suspended therein. But it has the advantage that there is no side effect that can occur when the food is used as a raw material and long-term use of the drug.

The food composition may further comprise a physiologically acceptable carrier. The type of carrier is not particularly limited, and any carrier conventionally used in the art can be used.

In addition, the food composition may contain additional components that are commonly used in food compositions and can improve odor, taste, visual appearance, and the like. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid and the like. Minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu) and chromium (Cr); And amino acids such as lysine, tryptophan, cysteine, valine, and the like.

In addition, the food composition may further contain antiseptic agents (such as potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate), bactericides (Sodium nitrite), bleach (sodium sulfite), seasoning (sodium MSG glutamate, etc.), sweeteners (dicin, cyclamate, saccharin, etc.), coloring agents , Sodium, etc.), perfume (vanillin, lactones, etc.), swelling agents (alum, potassium hydrogen D-tartrate), emulsifiers, thickeners (foams), encapsulating agents, gum bases, foam inhibitors, solvents, And may include food additives. The additives may be selected and used in appropriate amounts depending on the type of food.

As an example of the food composition of the present invention, it can be used as a health beverage composition. In this case, various flavors or natural carbohydrates can be added as an additional ingredient like ordinary beverages. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose, sucrose; Polysaccharides such as dextrin, cyclodextrin; Xylitol, sorbitol, erythritol, and the like. Sweeteners include natural sweeteners such as tau Martin and stevia extract; Synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate may be generally about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g per 100 ml of the health beverage composition of the present invention.

In addition to the above, the health beverage composition may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acid, protective colloid thickener, pH adjuster, stabilizer, Alcohols or carbonating agents, and the like. It may also contain flesh for the production of natural fruit juices, fruit juice drinks, or vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health beverage composition of the present invention.

Another object of the present invention is to provide a quasi-drug composition for preventing or ameliorating atopic dermatitis, which comprises a mixed extract of Hwangbuk, Kyeonggi, Gosam, Licorice, and McDonald or fractions thereof.

At this time, the definition of the above-mentioned yellow, white, red ginseng, licorice, ginseng, extract, fraction, atopic dermatitis, prevention and improvement is as described above.

The term "quasi-drug" of the present invention means a fiber, a rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or an animal, Or products similar to those which are not machinery, preparations used for sterilization, insecticides and similar uses for the prevention of infections, for the purpose of diagnosis, treatment, alleviation, treatment or prevention of diseases of human beings or animals Machinery, or apparatus, and that is not an apparatus, machine, or apparatus of an article used for the purpose of giving pharmacological effects to the structure or function of a person or animal, It also includes supplies.

When the extract of the present invention is added to a quasi-drug composition for the purpose of prevention or improvement of atopy, the extract may be added as it is or may be used in combination with other quasi-drugs, It can be used appropriately. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment).

The quasi-drug composition includes, but is not limited to, personal hygiene products, external preparation for skin, disinfectant cleaner, shower foam, wet tissue, detergent soap, hand wash, mask or ointment. The external preparation for skin is not particularly limited, but may be manufactured and used in the form of an ointment, a lotion, a spray, a patch, a cream, a powder, a suspension, a gel or a gel. The personal hygiene product may be, for example, a soap, a wet tissue, a tissue paper, a shampoo, a toothpaste, a hair care product, an air freshner gel, or a cleaning gel.

Another embodiment provides a cosmetic composition for preventing or ameliorating atopic dermatitis comprising a mixed extract of yellow whites, red ginseng, red ginseng, licorice, and ginseng root or fractions thereof.

At this time, the definition of the above-mentioned yellow, white, red ginseng, licorice, ginseng, extract, fraction, atopic dermatitis, prevention and improvement is as described above.

The mixed extracts of yellow, white, red ginseng, licorice, and ginseng can be contained in the composition in a proportion of 0.1% to 20% by weight based on the total weight of the composition, like the pharmaceutical composition. But are not limited to, specifically, from 0.1 wt% to 5 wt%, more specifically from 0.4 wt% to 0.6 wt%, and still more specifically, 0.5 wt% based on the total weight of the composition.

The ingredients of the cosmetic composition of the present invention include components commonly used in cosmetic compositions in addition to the above extracts. Examples of such ingredients include water, a surfactant, a moisturizer, a lower alcohol, a chelating agent, a bactericide, an antioxidant, And a flavoring agent. ≪ Desc / Clms Page number 7 >

In addition, the cosmetic composition may be prepared in any conventional formulation and may be in the form of solutions, emulsions, suspensions, pastes, creams, lotions, gels, powders, sprays, surfactant-containing cleansing, oils, But are not limited to, liquid cleansing agents, bath salts, foundation, makeup base, essence, lotion, foam, pack, suppositories, sunscreen cream or sun oil.

When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, or tracant may be used.

When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.

In addition, the ingredients contained in the cosmetic composition may be included in an amount commonly used in the skin science field.

The complex herbal medicine extract of the present invention can prevent, improve and treat atopic dermatitis because it exhibits an excellent effect of reducing the symptoms of atopic dermatitis erythema / bleeding, edema, dry / dry, abrasion / have.

FIG. 1 is a schematic diagram of an experiment for confirming the therapeutic effect of KAJA (a mixture of yellow, white, red ginseng, licorice and licorice extract) on atopic dermatitis. After induction of atopic dermatitis using DNCB, KAJA was orally administered.
Figure 2 is a graph showing the weight change of the mice during the treatment of KAJA. The results were expressed as mean ± SEM (n = 8).
Figure 3 is a graph showing changes in food intake of the mice during the treatment of KAJA. The results were expressed as mean ± SEM (n = 8).
FIG. 4 is an image showing the dorsal skin of a mouse observed after treating KAJA after induction of atopic dermatitis using DNCB.
Fig. 5 is a graph showing the skin thickness and the weight of the fleece after treatment with KAJA. *, **, or *** indicate P <0.05, P <0.01 or P <0.001, respectively, compared to the DNCB treated group. Results were expressed as mean ± SEM,
Figure 6 shows the effect of KAJA on skin infiltration of proinflammatory cells as an image of dorsal skin sections of mice stained with hematoxylin and eosin (H & E). Inflammatory cells were labeled with purple dots. Results are expressed as means ± SEM and *, **, or *** indicate P <0.05, P <0.01 or P <0.001, respectively, compared to DNCB treated group.
FIG. 7 shows the effect of KAJA on skin infiltration of mast cells in an image obtained by staining the back skin slice of a mouse with toluidine blue. Mast cells were labeled with purple dots. Results are expressed as means ± SEM and *, **, or *** indicate P <0.05, P <0.01 or P <0.001, respectively, compared to DNCB treated group.
Figure 8 shows the effect of KAJA on blood cell composition in blood and is a graph showing the number of WBCs, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Results are expressed as means ± SEM and *, **, or *** indicate P <0.05, P <0.01 or P <0.001, respectively, compared to DNCB treated group.
Figure 9 shows the effect of KAJA on the amount of plasma IgE expression. ** or *** indicates P < 0.01 or P < 0.001, respectively, compared to the DNCB treated group.
Figure 10 shows the effect of KAJA on the expression levels of plasma IL-6, IL-10 and IL-12. ** or *** indicates P < 0.01 or P < 0.001, respectively, compared to the DNCB treated group.
Figure 11 shows the effect of KAJA on mRNA expression of proinflammatory cytokines (IL-4, IL-6, IL-13 and TNF-a) in dermal tissues of mice and the like. Results are expressed as means ± SEM and *, **, or *** indicate P <0.05, P <0.01 or P <0.001, respectively, compared to DNCB treated group.
Figure 12 shows the effect of KAJA on the survival rate of RAW 264.7 macrophage (A) or HMC-1 cells (B), inflammation-related cells. The cells were treated with LPS (1 ㎍ / ㎖) for RAW264.7 cells, PMA (5 ng / ㎖) and ionomycin (500 ng / ㎖) for HMC-1 cells and incubated for 1 hour. Various concentrations of KAJA Was treated for 24 hours. After completion of the treatment, the survival rate of the cells was measured using the WST assay. The results are shown as means ± SEM, where A or B * or *** indicates P <0.05 or P <0.001, respectively, compared to the inflammatory control.
13 shows the results of comparing the survival rate reduction effect of the mixed herbal medicine extract (KAJA; A) and the herbal medicine extract alone, wherein A is inactivated HMC-1 cells, B is PMA (5 ng / The results are for HMC-1 cells activated to the inflammatory state by nomatic (500 ng / ml). Survival of HMC-1 cells was measured by MTT assays. The results are expressed as mean ± SEM, and ### indicates that P <0.001, *, ** and *** compared to the normal control group are inflammatory control groups P <0.05, P <0.01 and P <0.001, respectively.
14 shows the results of comparing the effect of reducing the survival rate of the inflammatory cells of the mixed herbal medicine extract (KAJA; A) and the herbal medicine extract alone. (100 μg / ml), or KAJA (A, 500 μg / ml) were treated with HMC-1 cells for 24 hours. Survival of HMC-1 cells was measured by MTT assays. The results are expressed as means ± SEM, and * indicates P <0.05 as compared to negative control.
FIG. 15 shows the results of comparing the effect of the mixed herbal medicine extract (KAJA; A) and the single herbal medicine extract for reducing the expression of proinflammatory cytokines. (100 ㎍ / ㎖), or KAJA (A, 500 ㎍ / ㎖) were treated for 24 hours. The mRNA expression levels of proinflammatory cytokines (IL-4, IL-6, IL-13 and TNF-α) in activated HMC-1 mast cells were confirmed by PCR. At this time, GAPDH was used as a loading control.
FIG. 16 shows the effect of reducing the survival rate of inflammatory cells according to the mixing ratio of herbal medicines constituting KAJA. 1: 1: 1: 1: 1 or 1: 1: 1: 1: 2 ratio of 1: 1: 1: 1: 1, 1: Quot; means a mixed herbal medicine extract which is contained in a weight ratio. Survival of HMC-1 cells was measured by MTT assays. The results are expressed as means ± SEM, and * indicates P <0.05 as compared to negative control.
FIG. 17 shows the effect of decreasing the expression of proinflammatory cytokines according to the mixing ratio of herbal medicines constituting KAJA. 1: 1: 1: 1: 1 or 1: 1: 1: 1: 2 ratio of 1: 1: 1: 1: 1, 1: Quot; means a mixed herbal medicine extract which is contained in a weight ratio. MRNA expression of proinflammatory cytokines (IL-4, IL-6, IL-13, and TNF-α) was detected in activated HMC-1 mast cells using GAPDH as the loading control.

Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

Manufacturing example  One. Of KAJA  Produce

KAJA was manufactured according to Good Manufacturing Practices (GMP) in Hanpung Pharmaceutical (Korea, Jeonju). KAJA is yellowish (Phellodendri Cortex), mold opening (Spica Schizonepetae), Sophora flavescens (Sophorae Radix), licorice (Glycyrrhizae Radix), and Extract powder was prepared by extracting water from a mixture containing Liriopis tuber at a weight ratio of 1: 1: 1: 1: 1, removing the solvent using a vacuum concentrator, and lyophilizing. The obtained powder was dissolved in water and used.

Example  One. Of KAJA  Toxicity check

To determine if KAJA causes toxicity or stress in mice, we observed changes in body weight and diet by oral administration of KAJA.

Specifically, experiments were conducted through a plan as shown in Fig. To induce acute allergic dermatitis, 1 x 1 cm sterile gauze was applied to the dorsal skin of 6-week-old male BALB / c mice and 100 μl of 2% DNCB was applied twice a week, followed by addition of 100 μl of 0.2% DNCB for 1 week 2 times for 3 weeks. All animal experiments related to mice were approved by Kyunghee University Experimental Animal Ethics Committee (Approval No.: KHUASP (SE) -14-014), and 6-week old BALB / c male mice (20 ± 2g) . The animals were housed in an animal room for 24 hours at a temperature of 24 ± 2 ° C and humidity of 40 to 60% for 12 hours. Four cages were housed in a mouse cage and fed sterile distilled water and solid feed freely. Two weeks before the end of the experiment, KAJA was orally administered at a fixed time every day, and the body weight and diet were measured twice a week.

As a result, no significant weight loss or dietary reduction was observed in both the normal control group, the DNCB treatment group and the KAJA treatment group, as shown in FIGS. 2 and 3. From the above results, it was found that KAJA does not cause toxicity or stress.

Example  2. Of KAJA  Assessing the efficacy of atopic dermatitis

To investigate the effect of KAJA on atopic dermatitis (AD), KAJA was orally administered to atopic dermatitis-induced mice of Example 1 for 2 weeks, and then the surface of the back skin was visually observed and the thickness And weighed.

Specifically, mice were sacrificed after photographing the back region of each mouse of each experimental group. After that, the back skin was excised and the skin thickness was measured with a digital caliper (Mitutoyo, Japan).

As a result, as shown in FIG. 4, the DNCB treated group had erythema / bleeding, edema, dry / dry, abrasion / erosion observed in the atopic dermatitis symptom, but the KAJA treated group was compared with the DNCB treated group , And skin hypersensitivity.

As can be seen from FIG. 5, the KAJA-treated group was found to be reduced to a superior degree of skin thickness, compared with the DNCB-treated group, and the weight of the jelly was also significantly decreased. And that it is dependent on the environment.

Example  3. Of KAJA  Infiltration inhibition of inflammatory cells and mast cells

Infiltration of inflammatory cells or mast cells into the skin induces allergic reactions and inflammation leading to skin hypersensitivity. Hematoxylin and eosin (H & E) and toluidine blue (T.B) staining were performed to confirm the inhibitory effect of KAJA on the infiltration of inflammatory cells and mast cells.

Specifically, a portion of the biopsy was fixed with 4% paraformaldehyde (PFA), and then frozen section compound (Frozen Section Compound, FSC22 Clear, Surgipath, Leica Biosystem, The Netherlands) A frozen section was prepared. The cells were stained with H & E to detect inflammatory cells, and stained with T.B to detect mast cells. The stained tissues were counted by high power fields (HPFs) at 5 fields / N (photos in each region) under X1000 magnification of the optical microscope, and the degree of inflammatory cell infiltration and mast cell changes were determined by cell / HPFs.

As a result, as shown in FIGS. 6 and 7, it was confirmed that the number of inflammatory cells and mast cells increased by DNCB treatment decreased in a concentration-dependent manner by KAJA treatment. These results show that KAJA has a remarkable effect on the treatment of atopic dermatitis as it reduces the number of inflammatory cells and mast cells, which are key cells in the allergic reaction, to an excellent extent.

Example  4. Of KAJA  Decreased effect of leukocyte count

High levels of white blood cells (WBCs) are observed in most patients with atopic dermatitis. Therefore, the number of WBCs present in the blood of the mice after KAJA treatment was analyzed to confirm the effect of KAJA on atopic dermatitis.

Specifically, a whole blood sample of the mouse was collected from the heart and stored in a Vacutainer (TM) tube containing EDTA (BD science, NJ, USA). The numbers of WBC, neutrophils, lymphocytes, monocytes, eosinophils or basophils were analyzed using a blood analyzer (Drew Scientific, Inc., Oxford, USA).

As a result, as shown in FIG. 8, it was confirmed that all the WBC, neutrophil, lymphocyte, mononuclear leukocyte, eosinophil and basophil were all increased in the mice treated with DNCB. However, it has been confirmed that the above-mentioned total leukocyte count is reduced to a very good level when KAJA orally administered, and this effect is confirmed to be dependent on the concentration of KAJA. As a result, KAJA showed a therapeutic effect of atopic dermatitis by decreasing leukocyte levels.

Example  5. Of KAJA IgE  And inflammatory cytokines.

Example  5-1. in vivo  Blood analysis

One of the hallmarks of AD is the high level of expression of serum IgE and inflammatory cytokines. Thus, in order to analyze the anti-inflammatory activity mechanism of KAJA, blood IgE and inflammatory cytokine levels of mice treated with DNCB were analyzed.

Specifically, blood was drawn from the heart and stored in EDTA tubes (Becton Dickinson Vacutainer system, USA). The plasma was separated from the blood by centrifugation at 2000 rpm for 10 minutes and stored at -80 ° C. until the experiment.

ELISA was performed to determine IgE and cytokine levels in the blood. ELISA plates were coated with each capture antibody contained in a coating buffer and stored at 4 캜 for one day. Thereafter, the cells were blocked with 5% FBS at room temperature for 1 hour, and the prepared plasma samples were diluted 20-fold and reacted at 100 μl volume for 2 hours at room temperature. At this time, IgE or cytokine recombinant protein which can confirm the concentration of IgE or cytokine in the blood was also reacted together. Each IgE or cytokine-detecting secondary antibody was added and incubated at room temperature for 1 hour. 100 μl of the substrate TMB solution was added and reacted for 15 minutes. After completion of the experiment, 50 μl of the final solution was added. Experimental results were measured on a 450 nm filter of an ELISA reader.

As a result, as shown in FIG. 9 and FIG. 10, it was confirmed that mice treated with DNCB showed an increase in cytokine levels of IL-6, IL-10 and IL-12 as well as IgE. However, it was confirmed that the level of IgE and cytokine was reduced to a good level in the mice treated with KAJA. In particular, it was confirmed that the cytokines of IL-6, IL-10 and IL-12 were reduced to a level similar to that of the normal control.

Example  5-2. in vivo mRNA  Expression level analysis

As shown in Example 5-1, KAJA reduced the amount of protein expression of IgE and inflammation-related cytokines in blood. Thus, in order to confirm whether KAJA regulates cytokine expression at the transcription level, Respectively.

Specifically, the amount of mRNA expression in the dorsal tissues of mice was analyzed. After the end of the experiment, the extracted tissues were pulverized with a homogenizer (IKA, China), RNA was extracted using an RNA isolation kit, RNA concentration was quantified with Nanodrop, and cDNA was synthesized with 1 μg of RNA. PCR was performed using 1 μl of the synthesized cDNA and the respective primers shown in Table 1 below.

Primer type Name of the primer division Primer sequence Mouse IL-2 SEQ ID NO: 1 F: 5'-GCA GCT GTT GAT GGA CCT AC-3 ' SEQ ID NO: 2 R: 5'-TCC ACC ACA GTT GCT GAC TC-3 ' IL-4 SEQ ID NO: 3 F: 5'-TCG GCA TTT TGA ACG AGG TC-3 ' SEQ ID NO: 4 R: 5'-GAA AAG CCC GAA AGA GTC TC-3 ' IL-6 SEQ ID NO: 5 F: 5'-CAA GAG ACT TCC ATC CAG TTG C-3 ' SEQ ID NO: 6 R: 5'-TTG CCG AGT TCT CAA AGT GAC-3 ' IL-13 SEQ ID NO: 7 F: 5'-CGG CAG CAT GGT ATG GAG TG-3 ' SEQ ID NO: 8 R: 5'-ATT GCA ATT GGA GAT GTT GGT CAG-3 ' TNF-a SEQ ID NO: 9 F: 5'-ATG AGC ACA GAA AGC ATG ATC-3 ' SEQ ID NO: 10 R: 5'-TAC AGG CTT GTC ACT GGA ATT-3 ' GAPDH SEQ ID NO: 11 F: 5'-GAG GGG CCA TCC ACA GTC TTC-3 ' SEQ ID NO: 12 R: 5'-CAT CAC CAT CTT CCA GGA GCG-3 '

As a result, as shown in FIG. 11, it was confirmed that the mice treated with DNCB increased the level of inflammation-related cytokines IL-4, IL-6, IL-13 and TNF-a. However, it was confirmed that the mRNA level of the cytokine in KAJA-treated mice was reduced to an excellent level, and the expression level of IL-6 was reduced to a level similar to that of a normal control. These results show that KAJA reduces the protein and mRNA expression of inflammation-related cytokines and thus shows a therapeutic effect of atopic dermatitis.

Example 6. Confirmation of Reducing Survival Rate of Inflammatory Cells of KAJA

To confirm the anti - inflammatory activity of KAJA, the survival rate of RAW 264.7 macrophages was analyzed using WTS assay.

Specifically, RAW 264.7 cells were dispensed to a 96-well culture plate in 1 × 10 ⁴ cells / well number, and cultured for 24 hours. Thereafter, each cell was activated to an inflammatory state by treating with 1 μg / ml of LPS in the presence or absence of various concentrations of KAJA. After 24 hours of incubation, 10 [mu] l of ez-cytox (DOGEN, Korea) was added to each well and the plates were incubated for additional 1 hour under dark conditions. The optical density was then measured at 450 nm using an ELISA reader (Versa Max, Molecular Devices, CA, USA).

As a result, as shown in Fig. 12A, it was confirmed that KAJA did not show toxicity to RAW 264.7 cells not treated with LPS. However, when RAW 264.7 cells treated with LPS were treated with KAJA, the number of RAW 264.7 cells decreased in a dose dependent manner. These results indicate that KAJA shows the therapeutic effect of atopic dermatitis by reducing the number of cells causing inflammation.

On the other hand, as shown in FIG. 12B, it was confirmed that the number of cells did not increase even when PMA and ionomycin, which are inflammation-inducing substances, were treated in HMC-1 cells. This confirms that HMC-1 cells do not undergo significant changes in the number of cells even when activated to the inflammatory state.

Example  7. Mixed crude drug extract ( KAJA ) And anti-inflammatory effects of herbal medicine extracts

Example 7-1. Reduction of Survival Rate of Inflammatory Cells

To confirm the antiinflammatory effect of KAJA, the effect of reducing the survival rate of HMC-1 mast cells activated to inflammatory state was compared with that of herbal medicine alone constituting KAJA.

Specifically, HMC-1 cells, which are mast cells, are treated with 5 g / ml of PMA and 500 ng / ml of ionomycin, after treating with Hwangbyeong, mungmundong, mold, gosam or licorice alone extract or KAJA, To an inflammatory state. After 24 hours of incubation, the survival rate of HMC-1 was confirmed by MTT assays.

As a result, as shown in Figs. 13 and 14, the extracts of Hwangbaek, myeongmundong, mold or licorice alone except for gosam did not affect the number of activated HMC-1 cells, whereas KAJA did not affect the number of activated HMC- Compared with the control group.

Example 7-2. Reduction effect of inflammatory cytokine expression level in inflammatory cells

In order to confirm the anti - inflammatory effect of KAJA, the effect of decreasing the expression level of proinflammatory cytokine was compared with that of herbal medicines alone constituting KAJA.

Specifically, HMC-1 cells were treated with 5 ng / ml of PMA and 500 ng / ml of ionomycin, respectively, after treating with Hwangbyeong, myeongmodong, mold, gosam or licorice alone extract or KAJA, Lt; / RTI &gt; After culturing for 24 hours, PCR was performed by the method according to Example 5-2.

As a result, as shown in FIG. 15, KAJA showed the expression levels of inflammatory cytokines IL-4, IL-6, IL-13 and TNF-α in comparison with extracts of Hwangbaek, , Respectively.

From the above results, it can be seen that the mixed herbal medicine extract of the present invention can reduce the inflammation to a superior extent as compared with the extracts of Hwangbyeong, Myeongmundong, Kyeonggi, Gosam or Licorice alone.

Example 8. Comparison of inflammation reduction effect according to the mixing ratio of KAJA

Example 8-1. Reduction of Survival Rate of Inflammatory Cells

The following experiment was conducted to confirm the mixing ratios of Hwangbyeong, Myeongmundong, Chunggi, Gosam and Licorice, which have the highest anti - inflammatory activity.

Specifically, a mixed herbal medicine extract (A1 or A2) containing, in a weight ratio of 1: 1: 1: 2: 1 or 1: 1: 1: 1: 2, Respectively. Subsequently, HMC-1 cells were treated with 5 ng / ml of PMA and 500 ng / ml of ionomycin in the presence or absence of 500 μg / ml of herbal extracts to activate each cell in an inflammatory state . After 24 hours of incubation, the viability of HMC-1 mast cells was confirmed by MTT assays.

As a result, as shown in FIG. 16, a mixed herbal medicine extract (A1) containing 1: 1: 1: 2: 1 or 1: 1: 1: 1: Or A2) did not affect the number of activated HMC-1 cells, whereas the mixed herbal medicine extract (KAJA; A) containing 1: 1: 1: 1: 1 contained the number of activated HMC- Compared with the control group.

Example 8-2. Reduction effect of inflammatory cytokine expression level in inflammatory cells

1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 12 hours in the same manner as in Example 8-1 to confirm the mixing ratios of yellow, white, (A1 or A2) containing 1: 2: 1 or 1: 1: 1: 1: 2 was prepared and treated with HMC-1 cells. Thereafter, after activation into an inflammatory state, PCR was performed by the method according to Example 5-2.

As a result, as shown in FIG. 17, mixed herbal medicine extracts (KAJA; A) containing 1: 1: 1: 1: 1 of yellow, white, MRNA expression levels of inflammatory cytokines such as IL-4, IL-6, IL-13 and TNF-α as compared to the herbal extracts (A1 or A2) contained in a weight ratio of 1: 1 or 1: 1: 1: As compared with the control.

From the above results, it was found that the mixed herbal medicine extract of the present invention is excellent in the inflammation-reducing effect when it contains 1: 1: 1: 1: 1 by weight ratio of Hwangbaek, Myeongmundong, Kyeonggi, Gosam and Licorice.

From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are to be considered in all respects as illustrative and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.

<110> University-Industry Cooperation Group of Kyung Hee University <120> A composition for treating atopic dermatitis comprising the          수비 <130> KPA160282-KR <160> 12 <170> KoPatentin 3.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IL-2 forward primer <400> 1 gcagctgttg atggacctac 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> IL-2 reverse primer <400> 2 tccaccacag ttgctgactc 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> IL-4 forward primer <400> 3 tcggcatttt gaacgaggtc 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> IL-4 reverse primer <400> 4 gaaaagcccg aaagagtctc 20 <210> 5 <211> 22 <212> DNA <213> Artificial Sequence <220> IL-6 forward primer <400> 5 caagagactt ccatccagtt gc 22 <210> 6 <211> 21 <212> DNA <213> Artificial Sequence <220> IL-6 reverse primer <400> 6 ttgccgagtt ctcaaagtga c 21 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> IL-13 forward primer <400> 7 cggcagcatg gtatggagtg 20 <210> 8 <211> 24 <212> DNA <213> Artificial Sequence <220> IL-13 reverse primer <400> 8 attgcaattg gagatgttgg tcag 24 <210> 9 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> TNF-a forward primer <400> 9 atgagcacag aaagcatgat c 21 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> TNF-a reverse primer <400> 10 tacaggcttg tcactggaat t 21 <210> 11 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> GAPDH forward primer <400> 11 gaggggccat ccacagtctt c 21 <210> 12 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> GAPDH reverse primer <400> 12 catcaccatc ttccaggagc g 21

Claims (11)

A pharmaceutical composition for the prevention or treatment of atopic dermatitis, which comprises as an active ingredient, a mixed extract of Porphyra yezoensis, Rhizoctonia sp. The composition according to claim 1, wherein the extract is obtained by extracting a mixture of yellowish white, red ginseng, red ginseng, licorice, and ginseng with at least one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof. The method according to claim 1, wherein the fraction is selected from the group consisting of water, a mixture of 1 to 4 carbon atoms, hexane, ethylacetate, chloroform, dichloromethane, Dichloromethane), and a mixed solvent thereof. 4. The method according to claim 2 or 3, wherein the mixture comprises a mixture of yellowish white, red ginseng, red ginseng, licorice and ginseng at a weight ratio of 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5: 0.5 to 1.5. Composition. The composition of claim 1, wherein the composition comprises from 0.001 to 80% by weight of a combined extract of yellow, white, red, ginseng, licorice, and marshmallow. 2. The composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient or diluent. The composition according to claim 1, wherein the composition is in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, Having any one of formulations selected from the group consisting of lotions, ointments, creams, patches, cataplasma, pastes, sprays, skin emulsions, skin suspensions, transdermal patches, drug-containing dressings and suppositories &Lt; / RTI &gt; A method for treating atopic dermatitis, comprising administering the composition of claim 1 to a suspected individual with atopic dermatitis other than human. A food composition for improving atopic dermatitis, comprising as an active ingredient, a mixed extract of Porphyra yezoensis, Rhizoctonia sp. A quasi-drug composition for preventing or ameliorating atopic dermatitis, which comprises as an active ingredient, a mixed extract of Hwangbuk, Brocoli, Gossam, Licorice, and McDonald or fractions thereof. A cosmetic composition for preventing or ameliorating atopic dermatitis, which comprises as an active ingredient, a mixed extract of Pseudomonas sp.

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