Pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus, and more specifically to a pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus, which contains ABT-751 or TN-16 as an active ingredient; a cosmetic composition for preventing or ameliorating allergic skin diseases or skin pruritus, which contains ABT-751 or TN-16 as an active ingredient; and a cosmetic composition for moisturizing the skin, which contains ABT-751 or TN-16 as an active ingredient. It has been confirmed that the composition for preventing, ameliorating, and treating atopic dermatitis according to the present invention effectively increases filaggrin expression in skin cells and improves skin barrier function, thereby effectively improving or treating the symptoms of allergic skin diseases including atopic dermatitis or skin pruritus, and also exhibits excellent skin moisturizing effects.

Description

[Technical Field]

[0001] The present invention relates to pharmaceutical compositions for the prevention or treatment of allergic skin diseases or pruritus, and more particularly to pharmaceutical compositions for the prevention or treatment of allergic skin diseases or pruritus, which contain ABT-751 or TN-16 as an active ingredient; cosmetic compositions for the prevention or amelioration of allergic skin diseases or pruritus, which contain ABT-751 or TN-16 as an active ingredient; and cosmetic compositions for moisturizing the skin, which contain ABT-751 or TN-16 as an active ingredient. [Background technology]

[0002] Atopic dermatitis is a chronic, recurring inflammatory skin disease that primarily begins in infancy or childhood. It is a widespread disease with 150 million patients in nine countries around the world, including the US, the UK, and China. The market for related therapeutic drugs is expected to grow to approximately 8 trillion won by 2025.

[0003] In South Korea, the number of patients receiving treatment for atopic dermatitis reaches 1 million each year, with the incidence rate being particularly high during infancy, with infants aged 0-4 years accounting for nearly 30% of all patients and children aged 9 and under accounting for half of all patients.

[0004] The increasing prevalence of atopic dermatitis both domestically and internationally is due in part to the high incidence rate, but also to the lack of accurate diagnostic methods and appropriate treatments. Currently, atopic dermatitis is diagnosed primarily through interviews or visual examinations, and treatment involves steroids or immunosuppressants, which are unrelated to the etiology. While immunosuppressants have relatively mild side effects, they cannot be prescribed to infants under the age of two, who have a particularly high incidence rate. Missing the early treatment window for infants, who desperately need early treatment, can lead to the prolongation and deepening of the disease.

[0005] To date, antibody treatments have been developed by global pharmaceutical companies, but they are limited to being prescribed only to severely ill patients aged 12 and over, and are not suitable for infants. This has led to the urgent need for a fundamental solution. Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention aims to provide a pharmaceutical composition containing ABT-751 or TN-16 as an active ingredient for preventing or treating allergic skin diseases or skin pruritus, a cosmetic composition containing ABT-751 or TN-16 as an active ingredient for preventing or ameliorating allergic skin diseases or skin pruritus, and a cosmetic composition containing ABT-751 or TN-16 as an active ingredient for moisturizing the skin. [Means for solving the problem]

[0007] The present invention provides a pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus, which comprises, as an active ingredient, a compound represented by the following chemical formula I or chemical formula II, or a pharmaceutically acceptable salt thereof: [Chemical formula I] [ka] [Chemical formula II] [ka]

[0008] In one embodiment of the present invention, the allergic skin disease may be atopic dermatitis or contact dermatitis.

[0009] In one embodiment of the present invention, the allergic skin disease may be atopic dermatitis.

[0010] In one embodiment of the present invention, the pharmaceutical composition may be administered by cutaneous application.

[0011] In one embodiment of the present invention, the atopic dermatitis may be caused by decreased expression of filaggrin.

[0012] In one embodiment of the present invention, when the reduction in filaggrin expression is 5.0% or more compared to normal individuals, the pharmaceutical composition may be administered to the patient.

[0013] In one embodiment of the present invention, the pharmaceutical composition may be in any dosage form selected from the group consisting of ointments, creams, lotions, gels, topical preparations, pastes, liniments, and air rolls.

[0014] The present invention also provides a cosmetic composition for preventing or ameliorating allergic skin diseases or skin pruritus, which contains a compound represented by the following chemical formula I or II as an active ingredient.

[0015] In one embodiment of the present invention, the cosmetic composition may be in any dosage form selected from the group consisting of a solution, an external ointment, a cream, a foam, a nourishing lotion, a softening lotion, a pack, a softening lotion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sunscreen oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a surfactant-containing cleanser, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, and a spray.

[0016] The present invention also provides a cosmetic composition for moisturizing skin, which contains a compound represented by the following chemical formula I or II as an active ingredient. [Chemical formula I] [ka] [Chemical formula II] [ka]

[0017] The present invention also provides a quasi-drug composition for moisturizing skin, which contains a compound represented by the following chemical formula I or II as an active ingredient. [Chemical formula I] [ka] [Chemical formula II] [ka] [Effects of the Invention]

[0018] It has been confirmed that the composition for preventing, ameliorating, and treating atopic dermatitis according to the present invention effectively increases filaggrin expression in skin cells and improves skin barrier function, thereby effectively improving or treating the symptoms of allergic skin diseases including atopic dermatitis or skin pruritus, and also exhibits excellent skin moisturizing effects. [Brief explanation of the drawings]

[0019] [Figure 1a] This relates to the increase in filaggrin expression levels due to ABT-751 treatment. [Figure 1b] This relates to the increase in filaggrin expression levels due to TN-16 treatment. [Figure 2] This is related to the increase in cell differentiation due to ABT-751 treatment. [Figure 3a] This study investigated the increase in filaggrin expression in the skin of HR-1 mice by ABT-751 treatment. [Figure 3b] This study investigated the increase in filaggrin expression in the skin of HR-1 mice by ABT-751 treatment. [Figure 3c] This is about the increase in filaggrin expression in the skin of HR-1 mice by TN-16 treatment. [Figure 4a]FIG. 1 shows a graph showing the reduction in skin water loss and increase in skin barrier index in HR-1 mice by application of a 4% formulation of ABT-751. [Figure 4b] FIG. 1 shows a graph showing the reduction in skin water loss and increase in skin barrier index in HR-1 mice by application of a 4% formulation of ABT-751. [Figure 4c] FIG. 1 shows a graph showing the reduction in skin moisture loss and increase in skin barrier index in HR-1 mice by application of 4% TN-16. [Figure 4d] FIG. 1 shows a graph showing the reduction in skin moisture loss and increase in skin barrier index in HR-1 mice by application of 4% TN-16. DETAILED DESCRIPTION OF THE INVENTION

[0020] The present invention will now be described in detail with reference to the accompanying tables and drawings.

[0021] When drawings are described, they are provided as examples to fully convey the concept of the present invention to those skilled in the art. Therefore, the present invention is not limited to the drawings shown, and may be embodied in other forms, and the drawings may be exaggerated to clarify the concept of the present invention.

[0022] Unless otherwise defined, the technical and scientific terms used herein have the meanings that are commonly understood by those having ordinary knowledge in the technical field to which this invention belongs, and in the following description and accompanying drawings, descriptions of well-known functions and configurations that may unnecessarily obscure the gist of the present invention will be omitted.

[0023] Also, as used in the present specification, the singular forms "a," "an," and "the" may be intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0024] Furthermore, unless otherwise specified, units used in the present specification are based on weight, and for example, units such as % or ratio mean % by weight or weight ratio.

[0025] In addition, in the specification of the present invention, the term "comprise" is an open-ended term that has the same meaning as terms such as "comprise," "contain," "comprise," "have," or "characterized by," and does not exclude any unrecited elements, materials, or processes. Furthermore, the term "consisting essentially of..." means that, together with the specified elements, materials, or processes, other unrecited elements, materials, or processes may be present in amounts that do not unacceptably affect at least one basic and novel technical idea of ​​the invention. Furthermore, the term "consisting of" means that only the recited elements, materials, or processes are present.

[0026] As used in the present specification, the terms "component", "composition", "composition of compound", "compound", "drug", "pharmaceutically active agent", "active agent", "cure", "therapy", "treatment" or "medication" are used interchangeably to mean a compound or a composition of compounds or substances that induces a desired pharmaceutical and / or physiological effect by local and / or systemic action when administered to a subject (human or animal).

[0027] As used herein, the term "treatment" or "therapy" (as well as its different forms) includes preventative (e.g., prophylactic treatment), curative, or palliative treatment. As used herein, the term "treating" includes alleviating or reducing at least one adverse or negative effect or symptom of a condition, disease, or disorder. The terms "prevention," "amelioration," and "treatment" of the present invention should be interpreted in the broadest sense, with "prevention" meaning not developing one or more clinical symptoms of a disease in a patient who is exposed to or susceptible to a disease but who has not yet experienced or manifested symptoms of the disease. "Treatment" refers to any action that arrests or reduces the onset of a disease or one or more of its clinical symptoms.

[0028] In the present invention, the terms "sample" and "specimen" refer to the subject of analysis, and are used interchangeably throughout the specification.

[0029] The present invention provides a pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus, which comprises, as an active ingredient, a compound represented by the following chemical formula I or chemical formula II, or a pharmaceutically acceptable salt thereof: [Chemical formula I] [ka] [Chemical formula II] [ka]

[0030] The compound I is a compound with CAS registration number 141430-65-1, which is ABT-751 (N-[2-[(4-hydroxyphenyl)amino]pyridin-3-yl]-4-methoxybenzenesulfonamide).

[0031] ABT-751 is an oral anti-cancer drug, a sulfonamide-containing antimitotic drug, which showed anti-tumor activity against a wide range of tumor cells and was developed as a treatment for breast cancer and non-small cell lung cancer, but development was subsequently discontinued.

[0032] The compound II is a compound with CAS registration number 33016-12-5, which is TN-16 (3-[1-(phenylamino)ethylidene]-5-(phenylmethyl)-2,4-pyrrolidinedione).

[0033] TN-16 is a novel microtubule inhibitor with antitumor activity. It was synthesized by modifying tenuazonic acid (3-acetyl-5-sec-butyltetramic acid), a natural antibiotic isolated and characterized from the culture of Alternaria tenuis. TN-16 was discovered to possess potent anticancer activity in 1967, but subsequent research failed to discover a more potent drug. Furthermore, in 1983, the mechanism of action of TN-16 was revealed to be through binding to sensitive sites by inhibiting microtubule formation. The structure of TN-16 is similar to that of cytocalin B, a standard actin polymerization inhibitor. It is known to induce cell cycle arrest at the M phase and suppress the cytotoxicity of T lymphocytes and spontaneously killing cells.

[0034] In the present invention, the pharmaceutically acceptable salt means a salt commonly used in the pharmaceutical industry, and examples thereof include inorganic ion salts prepared from calcium, potassium, sodium, magnesium, etc., inorganic acid salts prepared from hydrochloric acid, nitric acid, phosphoric acid, bromic acid, iodic acid, perchloric acid, sulfuric acid, etc., acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, carbonic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic ... Examples of suitable salts include, but are not limited to, organic acid salts prepared from taric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc.; sulfonate salts prepared from methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, etc.; amino acid salts prepared from glycine, arginine, lysine, etc.; and amine salts prepared from trimethylamine, triethylamine, ammonia, pyridine, picoline, etc.

[0035] According to the results of one embodiment of the present invention, the pharmaceutical composition not only promotes the expression level of filaggrin, which is highly associated with the onset of allergic skin diseases, and improves skin barrier function by promoting the skin's moisturizing effect, but also regulates the inflammatory response of allergic skin diseases and reduces skin itching, thereby demonstrating excellent effects in the prevention and treatment of allergic skin diseases, skin pruritus, or both.

[0036] Allergic skin diseases refer to pathological symptoms caused by allergic reactions mediated by mast cell activation, such as mast cell degranulation, and representative examples of such allergic skin diseases include atopic dermatitis and contact dermatitis.

[0037] Pruritus is a condition that can cause itching due to a decrease in the lipid content of the stratum corneum, which reduces the skin's antibacterial ability and barrier function, or itching caused by external stimuli such as temperature changes, chemicals, and electrical stimulation.

[0038] In the present invention, the term "anti-allergy" is used to mean the improvement (relief of symptoms), treatment, and prevention (suppression or delay of onset) of allergic skin diseases.

[0039] The allergic skin disease may be, for example, atopic dermatitis, which exhibits symptoms such as dry, eczematous skin and papules, and lesion samples from atopic patients show epidermal hyperplasia, epidermal proliferation, and accumulation of lymphocytes and mast cells. Patients with atopic dermatitis may develop severe skin pruritus, which causes inflammation of the skin lesions and further worsens the clinical symptoms.

[0040] Anatomically, the skin is the outermost layer of the body and serves as an important barrier, protecting the body from the external environment by blocking the direct inflow of airborne pathogens, viruses, and chemicals, and preventing excessive moisture loss. Skin tissue is layered into the basal layer, the spinous and granular layer, and the cornified layer, and specific expression markers are well known for each layer. Among these, keratin 1 (K1) and keratin 10 (K10) are expressed in the differentiated layer, while filaggrin is expressed in the top layer, the epithelium, including the stratum corneum. It is one of the key proteins essential for the formation of the skin's inherent barrier function, as described above.

[0041] In recent years, a correlation between atopic dermatitis and the filaggrin gene abnormalities has been identified in patients with the aforementioned atopic dermatitis. In Europe, in particular, mutations in the filaggrin gene have been detected in more than half of all atopic patients. In Japan, mutations in the filaggrin gene have been found in approximately 25% of atopic patients, and filaggrin gene mutations have also been detected in patients with dermatitis, including atopic dermatitis, in Asian countries such as China and Korea. It has been reported that such filaggrin gene abnormalities result in reduced expression of filaggrin protein in the skin and loss of skin barrier function, which facilitates the penetration of antigens such as allergens, leading to the development of dermatitis. In fact, atopic patients with filaggrin abnormalities are more likely to develop allergic diseases such as asthma and rhinitis, and therefore there is a need for the development of diagnostic methods and therapeutic agents that can determine the presence or absence of filaggrin gene abnormalities.

[0042] The atopic dermatitis may be caused by a decrease in filaggrin expression, and when the decrease in filaggrin expression is 5.0% or more compared to normal individuals, the pharmaceutical composition may be administered to the patient.

[0043] In a specific embodiment of the present invention, the compound represented by Formula I promotes the expression of filaggrin, enhances skin moisturizing effects, and exhibits excellent effects in improving the skin barrier index and skin overall index. Furthermore, in an allergic skin disease model, the compound not only significantly suppresses inflammatory responses, but also inhibits epidermal hyperplasia, epidermal proliferation, etc., regulates inflammatory cytokines, and reduces skin itching, thereby demonstrating excellent preventive, therapeutic, and ameliorative effects on allergic skin diseases and / or skin pruritus. Here, "inflammatory cytokine" refers to a cytokine that induces an inflammatory response generated in the body, as used in the technical field to which the present invention pertains. For example, IL-2, IL-4, and IL-13 can act as inflammatory cytokines in inducing allergic skin diseases.

[0044] For example, if the expression of filaggrin is reduced by 5.0% or more, preferably 5.3% or more, and more preferably 5.6% or more compared to a normal individual, the patient can be determined to be suffering from atopic dermatitis, and the patient may be administered the pharmaceutical composition of the present invention for the treatment of atopic dermatitis.

[0045] The pharmaceutical composition contains the compound represented by formula I or a pharmaceutically acceptable salt thereof, and may further contain suitable carriers, excipients, and diluents that are typically used in pharmaceutical compositions.

[0046] Carriers, excipients, and diluents that may be contained in the composition include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc. When the composition is formulated, it may be formulated using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc.

[0047] The pharmaceutical composition may be formulated into various forms by a conventional method and used. When formulated as a transdermal preparation, suitable dosage forms include, but are not limited to, ointments, creams, lotions, gels, external liquid preparations, pastes, liniments, and air rolls.

[0048] The pharmaceutical composition according to the present invention may further contain, in addition to the above-mentioned carriers, preservatives, stabilizers, wetting agents, emulsifiers, solubilizers, sweeteners, colorants, osmotic pressure adjusters, antioxidants and the like.

[0049] Formulation of pharmaceutical compositions is well known in the art, and reference may be made to Remington's Pharmaceutical Sciences (19th ed., 1995), etc., which is incorporated herein by reference.

[0050] The pharmaceutical compositions according to the present invention may be administered in a pharmaceutically effective amount.

[0051] In the present invention, a "pharmaceutically effective amount" refers to an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to any medical treatment. The effective dose level may be determined based on factors including the type and severity of the patient's disease, the activity of the drug, its sensitivity to the drug, the time of administration, the route of administration and excretion rate, the duration of treatment, concurrently used drugs, and other factors well known in the medical field. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, sequentially or simultaneously with conventional therapeutic agents, and may be administered in single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can achieve maximum effect with the minimum amount without side effects, which can be easily determined by one skilled in the art.

[0052] The pharmaceutical composition of the present invention may be administered to an individual via various routes. The mode of administration may be various dosage forms, such as oral and parenteral, and when formulated, may be formulated using commonly used excipients. Preferably, in the present invention, the pharmaceutical composition may be used as a parenteral formulation for skin application. The method of administration of the pharmaceutical composition of the present invention is determined by the type of drug as the active ingredient, as well as various related factors such as the disease to be treated, the administration route, the patient's age, sex, and weight, and the severity of the disease.

[0053] The present invention also provides a cosmetic composition for preventing or ameliorating allergic skin diseases or skin pruritus, comprising a compound represented by the following chemical formula I or chemical formula II or a pharmaceutically acceptable salt thereof as an active ingredient: [Chemical formula I] [ka] [Chemical formula II] [ka]

[0054] The cosmetic composition may be in any dosage form selected from the group consisting of, but not limited to, a solution, an ointment for external use, a cream, a foam, a nourishing lotion, a softening lotion, a pack, a softening lotion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sunscreen oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, and a spray.

[0055] Furthermore, the cosmetic composition of the present invention may additionally contain one or more cosmetically acceptable carriers that are typically incorporated into skin cosmetics, and may also contain, as appropriate, common ingredients such as oils, water, surfactants, moisturizers, lower alcohols, thickeners, chelating agents, pigments, preservatives, and fragrances, but is not limited to these.

[0056] The cosmetically acceptable carrier contained in the cosmetic composition of the present invention varies depending on the formulation.

[0057] When the dosage form of the present invention is an ointment, paste, cream or gel, the carrier component may be an animal oil, a vegetable oil, a wax, a paraffin, a starch, tragacanth, a cellulose derivative, a polyethylene glycol, a silicone, bentonite, silica, talc, zinc oxide or a mixture thereof.

[0058] When the dosage form of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, aluminum silicate, calcium silicate, polyamide powder, or a mixture thereof may be used as a carrier component, and particularly when the dosage form is a spray, a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether may also be included.

[0059] When the dosage form of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, in particular cottonseed oil, peanut oil, corn seed oil, olive oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycol or fatty acid esters of sorbitan.

[0060] When the dosage form of the present invention is a suspension, the carrier component may be a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester or polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth.

[0061] When the dosage form of the present invention is a soap, the carrier component may be an alkali metal salt of a fatty acid, a fatty acid hemiester salt, a fatty acid protein hydrolyzate, an isethionate salt, a lanolin derivative, a fatty alcohol, a vegetable oil, glycerol, or a sugar.

[0062] When the dosage form of the present invention is a surfactant-containing cleanser, the carrier component may be a fatty alcohol sulfate, a fatty alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyl taurate, a sarcositate, a fatty acid amide ether sulfate, an alkylamidobetaine, a fatty alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a lanolin derivative, or an ethoxylated glycerol fatty acid ester.

[0063] The cosmetic composition according to the present invention may contain colchicine in an amount of 0.01 to 20% by weight based on the total weight of the composition.

[0064] The present invention also provides a cosmetic composition for moisturizing skin, which contains, as an active ingredient, a compound represented by the following chemical formula I or II, or a pharmaceutically acceptable salt thereof: [Chemical formula I] [ka] [Chemical formula II] [ka]

[0065] The term "skin moisturizing" may refer to increasing the moisture content of the skin and maintaining a moist state, and the cosmetic composition for skin moisturizing according to the present invention has an excellent skin moisturizing effect of suppressing or reducing skin moisture loss, and exhibits excellent skin moisturizing effects by regulating the expression of factors related to moisturizing, such as filaggrin, involucrin, and loricrin.

[0066] The present invention also provides a quasi-drug composition for moisturizing skin, which contains, as an active ingredient, a compound represented by the following chemical formula I or II, or a pharmaceutically acceptable salt thereof: [Chemical formula I] [ka] [Chemical formula II] [ka]

[0067] The quasi-drug composition is a quasi-drug composition intended to moisturize the skin.

[0068] Quasi-drugs are items that are used for the purpose of diagnosing, curing, improving, mitigating, treating, or preventing diseases in humans or animals, and have a milder effect than pharmaceuticals. For example, according to the Pharmaceutical Affairs Act, quasi-drugs exclude items used for pharmaceutical purposes, and include, but are not limited to, fiber and rubber products used to treat or prevent diseases in humans and animals, items that have a mild or no direct effect on the human body, items that are not tools or machines or items similar to them, and disinfectants and insecticides used to prevent infectious diseases.

[0069] The type and dosage form of the quasi-drug composition of the present invention are not particularly limited, but are preferably disinfectants, shower foams, dental rinses (mouthwashes), wet tissues, detergent soaps, hand washes, humidifier fillers, masks, ointments, filter fillers, etc.

[0070] When the composition of the present invention is incorporated into a quasi-drug for skin moisturizing purposes, the composition may be used as is or together with other quasi-drug ingredients, or may be used appropriately according to a conventional method. The amount of the active ingredient to be mixed may be appropriately determined depending on the intended use, and the quasi-drug composition of the present invention may contain 0.01 to 20 wt % of the compound represented by Chemical Formula I or Chemical Formula II based on the total weight of the composition.

[0071] The present invention also provides a method for treating allergic skin diseases or skin pruritus, comprising the step of administering to a patient a pharmaceutical composition containing a compound represented by the following chemical formula I or chemical formula II, or a pharmaceutically acceptable salt thereof: [Chemical formula I] [ka] [Chemical formula II] [ka]

[0072] The treatment method can, for example, involve the steps of: a) measuring the expression level of filaggrin in a patient; and b) determining that the patient needs to be administered the pharmaceutical composition if the expression level of filaggrin is reduced by 5.0% or more compared to a normal individual, and then administering the pharmaceutical composition to the patient. However, this is not limited to this, and the amount and administration cycle of the pharmaceutical composition administered to the patient may vary depending on the amount of filaggrin reduced. As an example according to an embodiment of the present invention, the pharmaceutical composition may be administered at a concentration of 0.5 to 2.5 μM once a day for 1 to 4 weeks, but is not limited to this.

[0073] The present invention will be described in more detail below with reference to examples. It will be obvious to those skilled in the art that these examples are merely for the purpose of illustrating the present invention and should not be construed as limiting the scope of the present invention.

[0074] [Materials, Reagents, Strains, Equipment, etc.] The human epidermal cell line (Normal Human Epidermal Keratinocyte, NHEK) is a human fetal epidermal cell line provided by ATCC.

[0075] These cells were obtained from primary cultures and were used to confirm the intracellular biochemical changes induced by ABT-751 or TN-16 under normal conditions, rather than disease conditions.

[0076] -Experimental animals: hos:HR-1 (hairless) mice have the advantage of being hairless in skin disease research, allowing for direct application of drugs to the skin or induction of skin diseases with chemical or biological allergens for skin-related research.

[0077] In addition, the skin thickness at 8-10 weeks of age is approximately 0.4 mm, which is similar to human skin, and has the advantage of being useful for studying the pathological mechanisms of skin diseases and confirming biochemical changes in skin tissue.

[0078] [Test Example 1] 1.1. RNA extraction and filaggrin expression measurement using RT-qPCR Human epidermal keratinocyte cell line (NHEK) or mouse skin tissues treated with ABT-751, TN-16, or a control sample were lysed using TRI Reagent (MRC), and intracellular RNA was extracted using the Rneasy Mini Kit (Qiagen).

[0079] The extracted RNA was reverse transcribed using the ImProm-II™ Reverse Transcription Kit (Promega) to synthesize cDNA, and the amount of filaggrin was then measured by quantitative PCR (qPCR) using the Real-Time PCR Detection System (Bio-Rad, CFX96).

[0080] 1-2. Protein extraction and Western blotting A portion of the collected tissue was homogenized using a tissue homogenizer (Korea Scientific), then lysed using cell lysis buffer (RIPA buffer, Invitrogen), and centrifuged in a centrifuge (Labogene). The supernatant was transferred to a new tube and used as a protein sample.

[0081] 30 μg of protein sample was loaded onto a 4%-12% gradient PAGE gel (Invitrogen), and SDS-PAGE was performed using running buffer (Invitrogen) and an electrophoresis instrument (Bio-Rad) to separate the proteins by molecular weight.

[0082] The separated proteins were transferred onto a PVDF membrane (Bio-Rad) and then blocked with 5% blocking solution (Skimmilk, BD).

[0083] The thin film was reacted with a filaggrin antibody (Santa Cruz) or a GAPDH antibody (Abcam) for 16 hours, washed, and then reacted again with a secondary antibody for 1 hour and washed.

[0084] The thin film was reacted with ECL solution (Thermo Fisher), and the reacted proteins were detected using a luminescence reaction detector (Fusion Solo, Vilber).

[0085] [Test Example 2] Skin barrier function test Two hours after application of ABT-751 or TN-16, the amount of skin water loss at the application site, skin barrier index, and overall index were measured and recorded for three weeks using a precision measuring device (Courage-khazaka electronic GmbH, MPA10).

[0086] [Example 1] Filaggrin expression levels and cell differentiation in human epidermal cell lines treated with ABT-751 or TN-16 Cultured human epidermal cell line (NHEK) was treated with ABT-751 and TN-16, respectively, and filaggrin expression levels were measured to confirm changes in the degree of cell differentiation.

[0087] NHEKs were treated with ABT-751 and TN-16 at concentrations of 0, 0.5, 1.0, and 2.5 μM, respectively, and the filaggrin expression level and the degree of cell differentiation were observed 24 hours after treatment.

[0088] The results are shown in Figures 1 and 2.

[0089] These results confirmed that the level of filaggrin expression increased depending on the treatment concentration of ABT-751 and TN-16 (see Figure 1a and Figure 1b), and that the degree of cell differentiation was significantly increased in the ABT-751-treated group compared to the ABT-751-untreated group (control group) (see Figure 2).

[0090] [Example 2] Filaggrin expression level and cell differentiation degree in animal cells treated with ABT-751 or TN-16 ABT-751 and TN-16 in 0, 1, 2, and 4% formulations were applied to the dorsal skin of hairless hos:HR-1 mice (hereafter referred to as HR-1 mice) in equal amounts once daily for 3 weeks.

[0091] After each application, the skin moisture loss and skin barrier index were measured using the methods of the above test examples.

[0092] After 2 weeks of application, the HR-1 mice were euthanized in a carbon dioxide chamber, and the dorsal skin tissues were collected.

[0093] 2-1 Measurement of filaggrin expression level RNA and protein were extracted from the skin tissue to which ABT-751 or TN-16 had been applied, respectively, by the method of the above-mentioned test example, and the expression level of filaggrin was measured. The results are shown in FIG.

[0094] These results confirmed that, compared to the control group (0% formulation of ABT-751 or 0% formulation of TN-16), the expression level of filaggrin in skin tissue increased in a concentration-dependent manner after application of the remaining formulations of ABT-751 or TN-16 (see Figures 3a to 3c).

[0095] 2-2. Skin moisture loss and skin barrier index measurement The amount of skin water loss and skin barrier index were measured after application of the control group (0% formulation ABT-751 or 0% formulation TN-16) and 4% formulation ABT-751 or TN-16, respectively. The results are shown in Figure 4.

[0096] These results confirmed that application of 4% ABT-751 or TN-16 reduced skin moisture loss at the application site and increased the skin barrier index in HR-1 mice (see Figures 4a to 4d).

[0097] In particular, it was confirmed that the degree of reduction in skin moisture loss and the degree of increase in skin barrier index increased as the number of days of application increased.

[0098] Although certain parts of the present invention have been described in detail above, it will be apparent to those skilled in the art that these specific techniques are merely preferred embodiments and do not limit the scope of the present invention. Therefore, the true scope of the present invention can be defined by the appended claims and their equivalents.

Claims

1. A pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus, comprising a compound represented by the following chemical formula I or II, or a pharmaceutically acceptable salt thereof, as an active ingredient: [Chemical formula I] 【Chemistry 1】 [Chemical formula II] 【Chemistry 2】

2. 2. The pharmaceutical composition for preventing or treating an allergic skin disease or skin pruritus according to claim 1, wherein the allergic skin disease is atopic dermatitis or contact dermatitis.

3. 2. The pharmaceutical composition for preventing or treating an allergic skin disease or skin pruritus according to claim 1, wherein the allergic skin disease is atopic dermatitis.

4. 2. The pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus according to claim 1, which is administered by applying to the skin.

5. The pharmaceutical composition for preventing or treating allergic skin diseases or pruritus according to claim 1, wherein the atopic dermatitis is caused by decreased expression of filaggrin.

6. The pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus described in claim 5, characterized in that the pharmaceutical composition is administered to a patient when the decrease in filaggrin expression is 5.0% or more compared to normal individuals.

7. 2. The pharmaceutical composition for preventing or treating allergic skin diseases or skin pruritus according to claim 1, which is in any dosage form selected from the group consisting of ointments, creams, lotions, gels, topical liquids, pastes, liniments and air rolls.

8. A cosmetic composition for preventing or ameliorating allergic skin diseases or skin pruritus, comprising, as an active ingredient, a compound represented by the following chemical formula I or chemical formula II, or a pharmaceutically acceptable salt thereof: [Chemical formula I] 【Transformation 3】 [Chemical formula II] 【Chemistry 4】

9. 9. The cosmetic composition for preventing or ameliorating allergic skin diseases or skin pruritus according to claim 8, which is in any dosage form selected from the group consisting of a solution, topical ointment, cream, foam, nourishing lotion, softening lotion, pack, softening lotion, emulsion, makeup base, essence, soap, liquid cleanser, bath additive, sunscreen cream, sunscreen oil, suspension, emulsion, paste, gel, lotion, powder, soap, surfactant-containing cleansing oil, powder foundation, emulsion foundation, wax foundation, patch, and spray.

10. A cosmetic composition for moisturizing skin, comprising, as an active ingredient, a compound represented by the following chemical formula I or II, or a pharmaceutically acceptable salt thereof: [Chemical formula I] 【Transformation 5】 [Chemical formula II] 【Transformation 6】

11. A quasi-drug composition for moisturizing skin, comprising, as an active ingredient, a compound represented by the following chemical formula I or II, or a pharmaceutically acceptable salt thereof: [Chemical formula I] 【Transformation 7】 [Chemical formula II] 【Transformation 8】

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