KR20150006639A - Composition having ability to inhibit TSLP secretion and to improve allergic disease - Google Patents

Abstract

The present invention relates to a pharmaceutical composition, a cosmetic composition, or a functional health food composition which is effective in alleviating thymic stromal lymphopoietin (TSLP) secretion inhibiting ability and allergic disease by the TSLP inhibiting ability containing a compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. Accordingly, the composition has excellent TSLP secretion inhibiting effect which is an immune reaction factor, thereby having excellent mitigating effect of allergic disease induced by immune imbalance.

Description

[0001] The present invention relates to a composition having TSLP secretion inhibitory activity and an allergic disease-

The present invention relates to a pharmaceutical composition comprising at least one compound selected from the group consisting of atopic dermatitis, asthma, allergic rhinitis and allergic rhinitis caused by TSLP (Thymic stromal lymphopoietin) secretion inhibiting activity and TSLP secretion inhibiting activity, A cosmetic composition or a health functional food composition effective for the improvement of allergic diseases, including conjunctivitis, allergic dermatitis, allergic contact dermatitis, dermatitis or food allergy.

Recently, skin diseases have been greatly increased due to the increase of indoor living chemicals due to massive supply of artificial fibers as well as new environmental pollutants due to industrial development. In recent years, urban people have been suffering from a variety of diseases that cause immune hypersensitivity such as ticks in the carpet of the house, dust that increases due to the decrease of humidity, pet hair, pollen, new fruit and food, The chance of exposure to allergens is increasing. Allergic diseases such as atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis, dermatitis, or food allergy have been increasing in recent years and are attracting attention as they become social problems.

Allergic diseases refer to diseases caused by immune hyperresponsiveness, and include atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis, dermatitis or food allergy.

Allergic rhinitis is the most common allergic disease, and it is increasingly affecting the quality of life. It is a socioeconomic problem due to the decrease of the production capacity and the burden of the treatment cost, but there is no definite treatment. Drug therapy currently used is the basic treatment of allergic rhinitis, but recurrence is common and can cause serious side effects, and immunotherapy can be the primary treatment to restore the originally altered immune system, have.

On the other hand, asthma is a typical allergic disease such as allergic rhinitis. It is a chronic disease that causes airway irritation due to chronic inflammation of airway and intermittent airway constriction to cause respiratory distress symptoms. Asthma is caused by allergens (allergens) such as house dust mites and pollen which are present in the external environment, resulting in excessive inflammation of the airway mucosal tissues due to excessive immune reaction (allergic reaction), resulting in cough, dyspnea (Lemanske RF Jr., JAMA 1997, 278, 1855-1873). Recently, despite the development of immunology and molecular genetics, understanding the pathophysiology of asthma and developing new therapies, the prevalence of asthma is increasing. In particular, steroids or bronchodilators, which are used as conventional therapeutic agents, must be used for a long time as medicaments for the control and prevention of symptoms, not the fundamental healing of diseases, resulting in a great economic burden on individuals and society.

In addition, atopic dermatitis, also known as civilized disease or advanced country incurable disease, is a common worldwide disease that can occur in any age group. 70% to 95% of the disease develops in infants under 5 years of age. In Korea, the problem of atopic dermatitis has already reached serious social and medical problems. According to various reports, about 15% of the total population in Korea are atopic dermatitis patients, of which 18-22 per 100 children aged 0-4 years are known as atopic patients. More than 50% of patients with atopic dermatitis have atopic marches, ranging from allergic rhinitis to asthma.

Although the exact pathophysiology of allergic diseases including atopic dermatitis as described above has not yet been fully understood, it is thought that immunological and environmental factors will be involved with genetic predisposition. In particular, asthma, allergic rhinitis, atopic dermatitis Immunological imbalance is common in patients with the same allergic disease.

In addition, there are many reports that the exogenous atopic dermatitis, which accounts for the majority of atopic dermatitis, is caused by IgE-related immune mechanism, and delayed immune response due to T cell abnormality is involved rather than immediate type immune response to specific allergen. Because the main skin symptom of atopic dermatitis is eczematous lesions, it is not erythema and swelling appearing on the skin terminal test. Therefore, it is still controversial to evaluate the direct correlation of atopic dermatitis by the result of the immediate terminal type test. In addition, it has been reported that cell-mediated immune dysfunction is associated with IgE increase in atopic dermatitis patients, and delayed immune response due to T-cell abnormality is involved rather than immediate type immune response to specific allergens.

In patients with atopic dermatitis, cell-mediated immune disorders are known to occur up to 80%, and susceptibility to skin infections due to viruses and dermatophytes is increased and susceptibility to contact allergens tends to decrease. In the past, T cell maturation deficiency and the decrease in CD8 + T cell suppression have been reported as causes of CD4 + T cells in recent years. In other words, IL-4 that induces the production of IgE from B cells, IL-5 that stimulates IgE production from B cells, and IL-6 that amplifies IgE production are Th2 cells in CD4 + T cells, IL-4 and IL-13 secreted from these cells promoted the production of IgE, and IL-5 was expressed in the nucleus of the nucleus, (basophil) response (Source: Immunopathological mechanism of atopic dermatitis, Lee, Kwang-Hoon). According to recent reports, the immune response varies depending on the condition of atopic dermatitis. Th2 is involved in acute atopic dermatitis and Th1 in chronic atopic dermatitis. Initially, IL-4 and IL-13 secrete from Th2 play an important role. When they begin to scratch after itching, they migrate to Th1 cells.

In recent years, the increase of atopic dermatitis in adults as well as adults has become serious, and severe cases of social problems such as employment and marriage are causing severe social problems. In such cases, severe psychological stress can cause severe depression and avoidance of interpersonal abuse. Despite the fact that atopic dermatitis is a serious social and medical problem, there is no effective treatment until now.

Cyclosporin and FK506 (tacrolimus), which inhibit calcineurin and reduce cytokine expression, have been developed and used in the treatment of atopic dermatitis. However, they have weakened the immune system during long-term use, Steroid-based external remedies for relieving skin pruritus and pruritus also have problems such as decreased immunity and inhibition of growth when children are used for a long period of time. Therefore, there is a need for an effective therapeutic agent that is safe for long-term use and can alleviate or eliminate the root cause of atopic dermatitis.

Therefore, despite the fact that many researchers and researchers of Korean schools and biotech companies are studying and commercializing the ameliorative agents for improving atopic dermatitis, most of the developed products disappear in the early stage of market entry. This is because atopic dermatitis is induced and worsened rather than the development of a product corresponding to the pathological mechanism to enhance the moisturizing effect of the skin, or hypoallergenic cosmetics are being developed as atopic improvement products.

On the other hand, the underlying cause of allergic diseases is known as immune imbalance, which is the result of a variety of biological signal transduction. The highest protein of this abnormal signal transduction is Thymic stromal lymphopoietin (TSLP) cytokine. When allergens penetrate the body, substances such as TSLP stimulate the dendritic cells to react. In this process, symptoms of allergic diseases such as atopic dermatitis and asthma appear.

According to the known literature, TSLP protein and mRNA have been found to be increased in lesions of atopic dermatitis patients and have shown severe allergic diseases in human and animal models (mice) that have increased TSLP expression in skin (Steven F. Ziegler et al., J Allergy Clin Immunol, 2012; 130: 845-52). In addition, TSLP was detected in asthmatic patients bronchial washing solution, and there was a correlation between disease sensation and TSLP expression in airway epithelial cells. TSLP secreted from skin cells induced sensitization of allergic inflammatory reaction (Juan et al., Journal of Investigative Dermatology, 2012).

TSLP (Thymic stromal lymphopoietin) was first detected in cultures of thymus stromal cells as an IL-7-like cytokine. TSLP is mainly secreted from skin epidermal cells and skin epithelial cells as an important factor controlling the immune response at the interface between the body and the environment (skin, respiratory, digestive, eye, etc.). Recent studies have shown that TSLP is secreted in mast cells, airway smooth muscle, fibroblasts, and dendritic cells in addition to epithelial and epidermal keratinocytes to regulate the immune response Overexpression is known to cause immune imbalance.

Causes that promote TSLP secretion include viruses, bacteria and bacterial products, protease allergens, inflammatory cytokines, chemicals, and physical stimuli (scratching). , Overexpression causes immunological imbalance. The mechanisms causing immune imbalance are described below.

The TSLP receptor (TLSPR) is mainly expressed in hematopoietic cells and is most expressed in dendritic cells (DC). The expression of dendritic cells by TSLP increases the expression of major histocompatibility complex (II) molecules, co-stimulatory molecules CD86 and CD40, and increases expression of Th2 CD4 + T cells and naive CD4 CCL17 and CCL22 secretion, which increase T cell inflow, respectively, are increased. In addition, OX40L expression that increases Th2 differentiation is increased and IL-12 expression involved in Th1 differentiation is decreased. As a result, TSLP increases the induction of dendritic cells by the dendritic cells. It also increases the inflow of eosinophils, mast cells, natural killer T cells, and promotes the secretion of cytokines such as IL-13, thereby exacerbating immune imbalance.

Under the circumstances described above, the inventors of the present invention have investigated substances capable of improving immune imbalance, which is the fundamental cause thereof, for the effective treatment of allergic diseases. It has been found that the compound represented by Chemical Formula 1 is an overexpression of TSLP secretion regulating the immune response Thereby effectively alleviating allergic diseases such as atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis, dermatitis or food allergy. Completed.

It is an object of the present invention to provide a pharmaceutical composition for inhibiting secretion of TSLP comprising a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a cosmetic composition for inhibiting the secretion of TSLP comprising the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a method of inhibiting TSLP secretion or treating an allergic disease comprising the step of administering to a subject a composition containing the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient .

In order to solve the above problems, the present invention provides a pharmaceutical composition for inhibiting TSLP (Thymic stromal lymphopoietin) secretion comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Chemical Formula 1]

As used herein, the term " thymic stromal lymphopoietin "(TSLP) is an IL-7-like hematopoietic cytokine that is produced in epithelial cells, stromal cells and mast cells and is an important factor controlling the immune response of the human body. Thus, overexpression (hypersecretion) of TSLP in the human body including skin cells results in immunological imbalance, which may lead to onset and deepening of the onset of allergic diseases.

The term "Allergic disease " as used in the present invention means a disease caused by an allergic disease, that is, an allergic reaction (immune hypersensitivity reaction). Although the precise cause of the disease has not yet been elucidated, immune imbalance has been observed in most allergic diseases, and therapeutic agents or methods for treatment of immune imbalance have been actively studied.

The allergic diseases of the present invention include atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis, allergic conjunctivitis, contact dermatitis, urticaria, hives or food allergy.

The atopic dermatitis of the present invention is a chronic recurrent inflammatory skin disease, which is mainly in infancy or childhood, and is associated with pruritus (itching), dry skin, and characteristic eczema.

The asthma of the present invention is a condition in which the bronchus in the lung is very sensitive, and sometimes the bronchus becomes narrow, causing a breathing, rattling, and breathing sound, which causes severe coughing. It is an allergic disease.

The above-mentioned allergic rhinitis of the present invention indicates that the nasal mucosa exhibits an hypersensitivity reaction to a specific substance. After the causative substance (antigen) causing the allergy is exposed to the nasal mucosa, various kinds of IgE antibodies including mast cells, eosinophils Inflammatory cells mediate the inflammatory reaction caused by various mediators secreted by these means.

The allergic conjunctivitis of the present invention refers to a conjunctivitis caused by a local sensation, including conjunctival mild conjunctivitis, accompanied by swollen eyelid swelling and conjunctival swelling, particularly related to genetic susceptibility, Is referred to as allergic conjunctivitis.

The allergic dermatitis of the present invention refers to a disease that manifests symptoms of inflammation of the skin due to immunological hypersensitivity to allergen-causing substances.

The allergic contact dermatitis of the present invention refers to a skin disease in which irritable papules, erythema, or blisters appear on the skin of the abdomen, the oral cavity, the face, and the like due to the reaction of the skin upon contact with allergen- do.

The urticaria (urticaria) of the present invention refers to a skin disease in which permeability of blood vessels existing in the skin or mucous membranes is increased to temporarily accumulate plasma components in the tissues, resulting in redness or white swelling of the skin, and severe itching.

The food allergy of the present invention is an allergic reaction caused by food or food, and the symptoms may appear immediately after ingesting a food (a pseudo-allergen) that causes most of the allergic reaction, or may appear after a lapse of several hours.

The compound represented by the above formula (1) of the present invention, which is also referred to as Rhein, can be obtained by extracting or separating from a natural product, such as rhubarb, but is not limited thereto and can be chemically synthesized by a method known in the art, Can be used. The pharmacological activity of lanes is known to be effective for antipyretic, body temperature drop, antibacterial and edema.

In addition, the composition of the present invention preferably contains 0.0001 to 10% by weight of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof, based on 100% by weight of the total composition. If it is contained in an amount of less than 0.0001% by weight, there is a problem that the effect is too weak. On the other hand, when the content is more than 10% by weight, Can occur.

The pharmaceutical composition may have the ability to prevent or treat an allergic disease caused by immune imbalance.

In accordance with one embodiment of the present invention, it was confirmed that TSLP secretion was inhibited in a concentration-dependent manner by treatment of human keratinocytes induced with TSLP secretion according to the concentration of the compound represented by Formula 1, The cream containing the compound was applied to the atopic dermatitis patient for a certain period of time and showed an excellent improvement effect. This means that the composition containing the compound represented by the formula (1) of the present invention has an excellent effect on atopic dermatitis caused by immune imbalance by inhibiting the secretion of TSLP that regulates the immune response, and the compound Is useful as a therapeutic agent for TSLP secretion inhibitors or allergic diseases.

The term "prophylactic " as used in the present invention means any action which inhibits or delays disease by the administration of a composition containing the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof. The term "treatment" used in the present invention means all the actions of improving or ameliorating symptoms of a disease by administration of a composition containing the compound represented by the above-mentioned formula (1) or a pharmaceutically acceptable salt thereof.

The compound represented by formula (1) of the present invention can be used in the form of a pharmaceutically acceptable salt. Examples of such salts include acid addition salts formed by pharmaceutically acceptable free acids or metal salts formed by a base . As the free acid, an inorganic acid and an organic acid may be used. As the inorganic acid, hydrochloric acid, sulfuric acid, bromic acid, sulfurous acid, phosphoric acid or the like may be used. The metal salts include alkali metal salts or alkaline earth metal salts, and sodium, potassium or calcium salts are useful.

The composition of the present invention may contain, for administration, a pharmaceutically acceptable carrier, excipient or diluent in addition to the above-described effective ingredients. 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, microcrystalline cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The composition of the present invention may be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like oral preparation, external preparation, suppository or sterilized injection solution according to a conventional method. In detail, when formulating, it can be prepared using diluents or excipients such as fillers, weights, binders, humectants, disintegrants, surfactants and the like which are usually used. Solid formulations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, and the like. Such a solid preparation can be prepared by mixing at least one or more excipients such as starch, calcium carbonate, sucrose, lactose, gelatin and the like in the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof. 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 tasks. 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. As a base for suppositories, it is possible to use witepsol, macrosole, tween 61, cacao paper, laurin, glycerogelatin and the like.

Suitable doses of the compositions of the present invention will vary with the condition and weight of the patient, the severity of the disease, the form of the drug, and the time, but may be suitably selected by those skilled in the art. The daily dose of the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof is preferably 1 mg / kg to 500 mg / kg, and may be administered once or divided into several times, if necessary.

The present invention also provides a cosmetic composition having the ability to ameliorate an allergic disease by inhibiting the secretion of TSLP (Thymic stromal lymphopoietin), which comprises the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Chemical Formula 1]

Conventionally, when TSLP is over-expressed in human and animal skin, it can cause severe allergic diseases (atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, contact dermatitis or dermatitis) (Steven F. Ziegler et al., J Allergy Clin Immunol, 2012; 130: 845-52). It is also possible to influence the onset and progression of skin inflammation (such as atopic dermatitis and the like). In addition, TSLP secreted from skin cells induces an allergic inflammatory response and accelerates the onset of asthma when exposed to antigens (Juan et al., Journal of Investigative Dermatology, 2012).

Accordingly, the cosmetic composition containing the compound represented by the general formula (1) of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient inhibits overexpression of TSLP in the skin, thereby preventing atopic dermatitis, asthma, allergic rhinitis, , Allergic dermatitis, allergic contact dermatitis, chlamydia or allergic diseases of food allergy.

The cosmetic composition of the present invention may contain ingredients generally accepted in addition to the above-mentioned effective ingredients, and may include conventional additives such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers.

The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used in the form of solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, , Oil, powdered foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it can be manufactured in the form of a flexible lotion (skin), a nutritional lotion (milk lotion), a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder .

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 a polyamide powder may be used as a carrier component. In the case of a spray, in particular, chlorofluorohydrocarbons, propane / Propane or dimethyl ether.

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, agar or tracant, etc. may be used.

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

In addition, the present invention provides a health functional food composition having a TSLP (Thymic stromal lymphopoietin) secretion inhibiting effect, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Chemical Formula 1]

The health functional food composition of the present invention is useful as a preventive or remedy for allergic diseases including atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, contact dermatitis or dermatitis induced by immune imbalance .

The health functional food composition may contain various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, alginic acid and its salts , Organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices, synthetic fruit juices and vegetable drinks. These components may be used independently or in combination. The health functional food composition may be in the form of any one of meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcohol and vitamin complex Lt; / RTI >

In addition, the health functional food composition may further include a food additive, and the suitability of the food functional additive as a "food additive" Of the present invention.

Examples of the products that have been used in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, sensory coloring matter, licorice extract, crystalline cellulose, high- - Mixed preparations such as a sodium glutamate preparation, a noodle-added alkaline agent, a preservative preparation, a tar coloring agent and the like.

Herein, the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof according to the present invention, which is added to the food during the production of the health functional food composition, can be appropriately added or decreased as needed, By weight to 100% by weight to 1% by weight to 15% by weight.

The present invention also provides a TSLP secretion inhibiting method comprising the step of administering the above composition to a subject. Such administration may include oral administration, skin application or subcutaneous injection.

In addition, the present invention provides a method for treating an allergic disease comprising administering the composition to a subject. Such administration may include oral administration, skin application or subcutaneous injection.

In one embodiment of the present invention, a cosmetic composition containing the composition (a composition comprising the compound represented by formula (I) of the present invention) was prepared and applied continuously to the skin of a patient having atopic dermatitis for 8 weeks, There was a clear improvement of atopic dermatitis.

The composition containing the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to the present invention is excellent in the effect of inhibiting TSLP secretion as an immune response factor.

In addition, the composition of the present invention has excellent activity in the inhibition of secretion of TSLP, thereby modulating the immune response, thereby excellently relaxing the atopic dermatitis caused by immune imbalance.

Therefore, the composition containing the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to the present invention can be used as a TSLP secretion inhibitor or atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, Dermatitis, dermatitis, or allergies including food allergy.

FIG. 1 is a graph showing the inhibitory effect of TSHP secretion on human keratinocytes according to an embodiment of the present invention, by the concentration of Rhein, which is a compound represented by Chemical Formula 1. FIG.
FIG. 2 shows the results of cytotoxicity analysis of Rhein, a compound represented by Chemical Formula 1, on human keratinocytes according to an embodiment of the present invention.

Hereinafter, the present invention will be described in more detail with reference to the following experimental examples. However, the following experimental examples are intended to illustrate the present invention, and the scope of the present invention is not limited thereto.

The compound Rhein represented by Formula 1 of the present invention used in the following Experimental Examples was purchased from Sigma Aldrich, USA.

Experimental Example  1: Human keratinocyte TSLP  secretion Low performance  evaluation

Rhein, which is a compound represented by formula 1 of the present invention, was treated with human keratinocytes and cultured, and TSLP secretion inhibitory effect was confirmed.

After replacing with a new culture medium containing the CaCl ₂ in 1.4 mM concentration when chilled human keratinocytes (keratinocyte) the 24-well over 90% and incubated 4 days then put attachment by 1 × 10 ⁴ cell to the test plate 2 The cells were further cultured for one day to induce cell differentiation. To induce secretion of TSLP into differentiated cells, 20 ㎍ / ㎖ of poly I: C was treated. Lanes were then treated with 0.5 ㎍ / ㎖, 1 ㎍ / ㎖ or 2 ㎍ / ㎖, respectively. After 24 hours, cell culture was taken and TSLP concentration was measured by ELISA. The results are shown in Fig.

As shown in FIG. 1, the lane of the compound of formula 1 of the present invention showed TSLP secretion inhibition in a concentration-dependent manner. This means that the lane effectively inhibits TSLP secretion and thus has an immunomodulatory effect, thereby eliminating immunity imbalance.

Experimental Example  2: Evaluation of cytotoxicity of lane, which is a compound represented by formula (1)

To analyze the cytotoxicity of lanes, lanes were treated by concentration and cell viability was confirmed using a spectrophotometer.

After replacing with a new culture medium containing the CaCl ₂ in 1.4 mM concentration when chilled human keratinocytes (keratinocyte) the 24-well over 90% and incubated 4 days then put attachment by 1 × 10 ⁴ cell to the test plate 2 The cells were further cultured for one day to induce cell differentiation. After treatment with 20 ㎍ / ㎖ of poly I: C, lanes were treated with 0.5 ㎍ / ㎖, 1 ㎍ / ㎖ or 2 ㎍ / ㎖ respectively and cultured for 24 hours. After 24 hours, the medium was removed, and 200 μl of the culture medium and 20 μl of the CCK8 solution were added to each well. Then, the culture was incubated for 20 minutes at 37 ° C. in a CO ₂ atmosphere, and the absorbance was measured at 450 nm. The effect of lanes on cell viability was evaluated based on the absorbance of poly I: C treated wells. The results are shown in Fig.

As shown in Fig. 2, lanes did not cause cytotoxicity at the experimental concentrations. This means that the lane is less likely to cause skin irritation and is a safe material.

Experimental Example 3: Improvement effect of atopic dermatitis on cosmetic composition containing lane, which is a compound represented by formula (1)

In order to confirm the effect of improving the atopic dermatitis of the cosmetic composition containing lane, the experiment was carried out on 20 men and women having atopic dermatitis after preparing the cream at the ratio shown in Table 1 below.

Composition Example (% by weight) Comparative Example (% by weight) lane 1.0 - Stearic acid 15.0 15.0 Cetanol 1.0 1.0 Primary potassium oxide 0.7 0.7 glycerin 5.0 5.0 Propylene glycol 3.0 3.0 antiseptic Suitable amount Suitable amount incense Suitable amount Suitable amount Purified water Total 100 Total 100

Fifteen of 20 adult males and 20 females applied the cream containing the lane of the example at intervals of 12 hours to 14 hours to the lesion for 8 weeks (experimental group) in the ratio shown in Table 1 above, and the remaining 5 contained the lane of the comparative example Uncreamed cream was applied to the affected area for 8 weeks (control group). Thereafter, the degree of severity of atopic dermatitis was judged by interview and visual examination, and the degree of improvement of atopic dermatitis was evaluated in three stages of marked effect, effect, and no difference. The results are shown in Table 2 below.

Distinct effect (n.) Effective (persons) No difference (persons) Experimental group (containing lane) 7 5 3 Control group (rain-free) 0 One 4

As shown in the above Table 2, the experimental group to which the cream of the example including the lane, which is the compound represented by the formula 1, applied the cream showed better atopic dermatitis improving effect than the control group which did not include the lane of the comparative example . Therefore, the compound represented by the formula (1) of the present invention can be usefully used as an atopic dermatitis remedy.

Claims (11)

A pharmaceutical composition for inhibiting the secretion of TSLP (Thymic stromal lymphopoietin) comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

The pharmaceutical composition according to claim 1, wherein the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof is contained in an amount of 0.0001 to 10% by weight based on 100% by weight of the total composition.
The pharmaceutical composition according to claim 1, wherein the composition has the ability to prevent or treat an allergic disease caused by immune imbalance.
The pharmaceutical composition according to claim 1, wherein the allergic disease is atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis or dermatitis.
A cosmetic composition having the ability to improve an allergic disease by inhibiting TSLP (Thymic stromal lymphopoietin) secretion, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

The cosmetic composition according to claim 5, wherein the allergic disease is atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis or dermatitis.
1. A health functional food composition having a TSLP (Thymic stromal lymphopoietin) secretion inhibitory effect comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

The health functional food composition according to claim 7, wherein the composition has the ability to prevent or ameliorate an allergic disease.
The health functional food composition according to claim 7, wherein the composition has the ability to prevent or ameliorate an allergic disease.
A method for inhibiting TSLP secretion comprising administering to a subject a composition of any one of claims 1 to 9.
9. A method of treating an allergic disease comprising administering to a subject a composition of any one of claims 1 to 9.

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