Pharmaceutical composition for the prevention or treatment of allergic skin diseases or 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 a pharmaceutical composition for preventing or treating allergic skin diseases or pruritus, and more particularly, to a pharmaceutical composition for preventing or treating allergic skin diseases or pruritus containing ABT-751 or TN-16 as an active ingredient, a cosmetic composition for preventing or improving allergic skin diseases or pruritus containing ABT-751 or TN-16 as an active ingredient, and a cosmetic composition for skin moisturizing containing ABT-751 or TN-16 as an active ingredient, etc.

Background Art

[0002] Atopic dermatitis is a chronic and recurrent inflammatory skin disease that mainly starts in infancy or childhood. It is a disease with a large number of patients, reaching 150 million patients in 9 countries around the world such as the United States, the United Kingdom, and China. The related therapeutic drug market is expected to grow to about 8 trillion won by 2025 in the future.

[0003] In the case of Korea, the number of patients receiving medical treatment for atopic dermatitis reaches 1 million every year. In particular, the incidence rate is high in infancy, and infants aged 0 to 4 account for nearly 30% of the total, and child patients under 9 years old account for half of the total.

[0004] The reasons for the increasing prevalence of atopic dermatitis at home and abroad include the high incidence rate, but also the absence of diagnostic methods that can accurately diagnose the etiology and appropriate treatment methods. Currently, the diagnosis of atopic dermatitis is mainly carried out by inquiry or visual examination, and treatment methods also use steroid agents or immunosuppressive agents that have nothing to do with the etiology. In the case of immunosuppressive agents, the side effects are not particularly severe, but they cannot be prescribed to infants under 2 years old, who have a particularly high incidence rate. By missing the treatment period of infants who urgently need early treatment in the early stage of onset, it will lead to the prolongation and deepening of the disease.

[0005] To date, antibody therapies have been developed by global pharmaceutical companies, but they are mainly only available for severely ill patients aged 12 and older, and are not applicable to infants and young children. There is a pressing need to prepare a fundamental solution to this problem. [Overview of the Initiative] [Problems that the invention aims to solve]

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

[0007] The present invention provides a pharmaceutical composition for the prevention or treatment of allergic skin diseases or 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]

[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 topical application to the skin.

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

[0012] In one embodiment of the present invention, if the reduction in filaggrin expression is 5.0% or more compared to a normal person, 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 roll preparations.

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

[0015] In one embodiment of the present invention, the cosmetic composition may be any dosage form selected from the group consisting of solutions, topical ointments, creams, foams, nourishing lotions, softening lotions, packs, softening waters, makeup bases, essences, soaps, liquid cleansers, bath additives, sunscreen creams, sunscreen oils, suspensions, emulsions, pastes, gels, lotions, powders, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, patches, and sprays.

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

[0017] Furthermore, the present invention provides a quasi-drug composition for skin moisturization containing, as an active ingredient, a compound represented by the following Chemical Formula I or Chemical Formula II. [Chemical Formula I]

Chem.

Chem.

Advantages of the Invention

[0018] The composition for preventing, ameliorating, or treating atopic dermatitis according to the present invention effectively increases the expression of filaggrin in skin cells and improves the skin barrier function, thereby effectively ameliorating or treating the symptoms of allergic skin diseases or skin pruritus including atopic dermatitis, and has been confirmed to exhibit an excellent skin moisturizing effect.

Brief Description of the Drawings

[0019] [Figure 1a] It relates to the increase in the filaggrin expression level by ABT-751 treatment. [Figure 1b] It relates to the increase in the filaggrin expression level by TN-16 treatment. [Figure 2] It relates to the increase in cell differentiation degree by ABT-751 treatment. [Figure 3a] It relates to the increase in the filaggrin expression level in the skin of HR-1 mice by ABT-751 treatment. [Figure 3b] It relates to the increase in the filaggrin expression level in the skin of HR-1 mice by ABT-751 treatment. [Figure 3c] It relates to the increase in the filaggrin expression level in the skin of HR-1 mice by TN-16 treatment. [Figure 4a]This figure shows the reduction in skin water loss and increase in skin barrier index in HR-1 mice after application of the 4% dosage form of ABT-751. [Figure 4b] This figure shows the reduction in skin water loss and increase in skin barrier index in HR-1 mice after application of the 4% dosage form of ABT-751. [Figure 4c] This figure shows the reduction in skin water loss and increase in skin barrier index in HR-1 mice after application of TN-16 in a 4% dosage form. [Figure 4d] This figure shows the reduction in skin water loss and increase in skin barrier index in HR-1 mice after application of TN-16 in a 4% dosage form. [Modes for carrying out the invention]

[0020] The present invention will be described in detail below with reference to the attached tables or drawings.

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

[0022] In this context, unless otherwise defined, technical and scientific terms used here have the meaning that a person with ordinary skill in the art to which this invention belongs would ordinarily understand. In the following description and accompanying drawings, descriptions of known functions and configurations that could unnecessarily obscure the essence of this invention are omitted.

[0023] Furthermore, unless otherwise specified in the specification of this invention, the singular form may also be intended to include the plural form.

[0024] Furthermore, units used in the specification of this invention unless otherwise specified are based on weight, and for example, units of % or ratio mean weight percent or weight ratio.

[0025] Furthermore, in the specification of this invention, the expression "includes" is an open statement equivalent to expressions such as "equips," "contains," "equips," "has," or "characterizes," and does not exclude any elements, materials, or processes that are not enumerated. Also, the expression "substantially consists of..." means that other elements, materials, or processes that are not enumerated may be present in quantities that do not imperceptibly affect at least one fundamental and novel technical idea of ​​the invention, along with the specified elements, materials, or processes. Also, the expression "consists of" means that only the described elements, materials, or processes exist.

[0026] As used in the specification of this invention, the terms “component,” “composition,” “composition of compounds,” “compound,” “drug,” “pharmaceutical activator,” “activator,” “cure,” “treatment,” “therapy,” or “pharmaceutical” are interchangeable to mean a compound or a composition of a compound or substance that, when administered to a subject (human or animal), induces a desired pharmaceutical and / or physiological effect by local and / or systemic action.

[0027] As used herein, the terms “treatment” or “therapy” (and its different forms) include preventive (e.g., preventive treatment), curative, or mitigating treatments. As used herein, “to treat” includes reducing or decreasing at least one harmful or negative effect or symptom of a condition, disease, or disorder. The terms “prevention,” “improvement,” and “treatment” in this invention should be interpreted in their broadest sense, “prevention” means preventing the progression of one or more clinical symptoms of a disease in a patient who is exposed to or susceptible to the disease but has not yet experienced or manifested any symptoms of the disease. “Treatment” means any action that prevents or reduces the onset of a disease or one or more clinical symptoms thereof.

[0028] In this invention, "sample" or "sample" refers to the subject of analysis and is used with the same meaning throughout the specification.

[0029] The present invention provides a pharmaceutical composition for the prevention or treatment of allergic skin diseases or 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]

[0030] The aforementioned compound I is compound ABT-751 (N-[2-[(4-Hydroxyphenyl)amino]pyridin-3-yl]-4-methoxybenzenesulfonamide), which has CAS registry number 141430-65-1.

[0031] ABT-751 is an anticancer drug developed for oral use, containing a sulfonamide and being an antimitotic drug. It exhibited antitumor 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] Compound II is the compound with CAS registry 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, synthesized by modifying tenuazonic acid (3-acetyl-5-sec-butyltetramic acid), a natural antibiotic isolated and characterized from Alternaria tenuis cultures. While TN-16 was discovered to possess potent anticancer activity in 1967, subsequent research has not yielded any more potent drugs. Furthermore, in 1983, it was revealed that TN-16 acts by inhibiting microtubule formation, thereby binding to and acting on sensitive sites. The structure of TN-16 is similar to that of cytocalin B, a standard actin polymerization inhibitor, and it is known to induce cell cycle arrest in M ​​phase and suppress cytotoxicity of T lymphocytes and spontaneously killed cells.

[0034] In this invention, pharmaceutically acceptable salts mean salts commonly used in the pharmaceutical industry, and examples include inorganic ion salts produced from calcium, potassium, sodium, and magnesium, inorganic salts produced from hydrochloric acid, nitric acid, phosphoric acid, bromate, iodic acid, perchloric acid, and sulfuric acid, 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 acid, and glutamic acid. Examples include, but are not limited to, organic salts produced from taric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc.; sulfonates produced from methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, etc.; amino acid salts produced from glycine, arginine, lysine, etc.; and amine salts produced 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 of filaggrin, which is highly associated with the onset of allergic skin diseases, and improves the skin barrier function by promoting the moisturizing effect of the skin, but also modulates the inflammatory response of allergic skin diseases and reduces skin itching, thereby exhibiting excellent effects in the prevention and treatment of allergic skin diseases, pruritus, or both.

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

[0037] Pruritus is a condition that includes itching caused by a decrease in the lipid content of the stratum corneum of the skin, resulting in reduced antibacterial activity and impaired barrier function, or itching caused by external stimuli such as temperature changes, chemicals, or electrical stimulation.

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

[0039] The aforementioned allergic skin disease may include, for example, atopic dermatitis. Atopic dermatitis presents with 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 pruritus, which causes inflammation of skin lesions and further worsens clinical symptoms.

[0040] The skin is anatomically the outermost layer of the body and plays a crucial barrier function, protecting the body from the external environment by blocking the direct influx of pathogenic microorganisms, viruses, and chemicals from the air, and preventing excessive leakage of bodily fluids. Skin tissue has a layered structure consisting of 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 spinous and granular layer, while filaggrin is expressed in the uppermost epithelium, including the cornified layer, and is one of the major proteins essential for forming the skin's unique barrier function described above.

[0041] In recent years, a correlation between atopic dermatitis and filaggrin gene abnormalities has been revealed in patients with atopic dermatitis, and in Europe in particular, mutations in the filaggrin gene have been detected in more than half of all atopic dermatitis patients. In Japan, it has also been revealed that more than 25% of atopic dermatitis patients have mutations in the filaggrin gene, and in Asian countries including China and South Korea, mutations in the filaggrin gene have been detected in patients with dermatitis, including atopic dermatitis. It has been reported that such filaggrin gene abnormalities lead to decreased expression of filaggrin protein in the skin and loss of skin barrier function, making it easier for antigens such as allergic irritants to penetrate and causing dermatitis. In fact, among atopic dermatitis patients, those with filaggrin abnormalities are more likely to progress to allergic diseases such as asthma and rhinitis, and 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 if the decrease in filaggrin expression is 5.0% or more compared to a normal person, the patient may be administered the pharmaceutical composition.

[0043] In specific embodiments of the present invention, the compound represented by chemical formula I promotes filaggrin expression, enhances skin moisturizing effects, and exhibits excellent improvement effects in terms of skin barrier index and overall skin index. Furthermore, it not only significantly suppresses inflammatory responses in allergic skin disease models, but also suppresses epidermal hyperplasia, epidermal proliferation, etc., regulates inflammatory cytokines, reduces skin itching, and exhibits excellent preventive, therapeutic, and ameliorative effects against allergic skin diseases and / or pruritus. Here, inflammatory cytokines refer to cytokines that induce inflammatory responses occurring in the body, and are used in the usual sense in the art to which the present invention belongs. For example, IL-2, IL-4, and IL-13 can act as inflammatory cytokines in inducing allergic skin diseases.

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

[0045] In addition to containing the compound represented by formula I or a pharmaceutically acceptable salt thereof, the pharmaceutical composition may further include suitable carriers, excipients, and diluents commonly used in pharmaceutical compositions.

[0046] The carriers, excipients, and diluents that may be included in the above 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, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. When the above composition is put into dosage form, it may be put into dosage form using commonly used fillers, bulking agents, binders, wetting agents, disintegrants, surfactants, or other diluents or excipients.

[0047] The aforementioned pharmaceutical composition may be used in various dosage forms by conventional methods. When it is formulated as a transdermal agent, preferred dosage forms include, but are not limited to, ointments, creams, lotions, gels, topical solutions, pastes, liniments, and air rolls.

[0048] The pharmaceutical composition according to the present invention may further include, in addition to the carrier, a preservative, a stabilizer, a wetting agent, an emulsifier, a solvent, a sweetener, a coloring agent, an osmotic pressure regulator, an antioxidant, and the like.

[0049] Regarding the formulation of pharmaceutical compositions into dosage forms, this is publicly known in the industry, and specific examples may be found in literature such as [Remington's Pharmaceutical Sciences (19th ed., 1995)]. The aforementioned literature is considered part of this specification.

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

[0051] In the present invention, “pharmaceutically effective amount” means an amount sufficient to treat a disease with a reasonable benefit-to-risk ratio applicable to medical treatment, and 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, the patient’s sensitivity to the drug, the time of administration, the route of administration and elimination rate, the duration of treatment, drugs used concurrently, and other factors well known in the medical field. The pharmaceutical compositions according to the present invention may be administered as individual therapeutic agents, in combination with other therapeutic agents, sequentially or concurrently with conventional therapeutic agents, and in single or multiple doses. It is important to administer an amount that takes all of the above factors into consideration and provides the greatest effect with the minimum amount without side effects, which can be easily determined by those 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, for example, in various oral and parenteral dosage forms. When forming a dosage form, the excipients commonly used may be used. Preferably, in the present invention, it may be used as a parenteral preparation, specifically as a topical preparation for skin application. The method of administering the pharmaceutical composition of the present invention is determined by the type of drug that is the active ingredient, along with various relevant factors such as the disease being treated, the route of administration, the patient's age, sex, and weight, and the severity of the disease.

[0053] Furthermore, the present invention provides a cosmetic composition for the prevention or improvement of allergic skin diseases or pruritus, which contains 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, but is not limited to, any dosage form selected from the group consisting of solutions, topical ointments, creams, foams, nourishing lotions, softening lotions, packs, softening waters, makeup bases, essences, soaps, liquid cleansers, bath additives, sunscreen creams, sunscreen oils, suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, patches, and sprays.

[0055] Furthermore, the cosmetic composition of the present invention may additionally include one or more cosmetically acceptable carriers commonly used in skin cosmetics, and may appropriately contain, but is not limited to, oils, water, surfactants, humectants, lower alcohols, thickeners, chelating agents, pigments, preservatives, fragrances, and the like as usual ingredients.

[0056] The cosmetically acceptable carriers included in the cosmetic composition of the present invention vary depending on the dosage form.

[0057] When the dosage form of the present invention is an ointment, paste, cream, or gel, animal oils, vegetable oils, waxes, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, or mixtures thereof may be used as the carrier component.

[0058] When the dosage form of the present invention is a powder or a spray, the carrier component may be lactose, talc, silica, aluminum hydroxide, aluminum silicate, calcium silicate, polyamide powder, or a mixture thereof. In particular, when it is a spray, it may further include propellants such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

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

[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, or microcrystalline cellulose, aluminum methhydroxyl, bentonite, aga, or tragacanth.

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

[0062] When the dosage form of the present invention is a surfactant-containing cleanser, the carrier component may be an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinate monoester, isethionate, imidazolinium derivative, methyl taurate, sarcositate, fatty acid amide ether sulfate, alkylamide betaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or 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 relative to the total weight of the composition.

[0064] Furthermore, the present invention provides a skin moisturizing cosmetic composition containing 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]

[0065] The aforementioned skin moisturizing can mean increasing the moisture level of the skin and maintaining a moist state. The skin moisturizing cosmetic composition according to the present invention has an excellent skin moisturizing effect that suppresses or reduces the loss of skin moisture, and exhibits a superior effect on skin moisturizing by regulating the expression of moisturizing-related factors such as filaggrin, involucrin, and loricrin.

[0066] Furthermore, the present invention provides a quasi-drug composition for skin moisturizing that contains 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]

[0067] The aforementioned quasi-drug composition is a quasi-drug composition intended for skin moisturizing.

[0068] The aforementioned quasi-drugs refer to articles used for the purpose of diagnosing, treating, improving, alleviating, managing, or preventing diseases in humans or animals, which have a milder effect than pharmaceuticals. For example, according to the Pharmaceutical Affairs Law, quasi-drugs are articles excluding those used for pharmaceutical purposes, and include, but are not limited to, textile and rubber products used for the treatment or prevention of diseases in humans and animals, items that have a mild or no direct effect on the human body, items that are not instruments or machines and similar items, 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 wipes, detergents, hand washes, humidifier fillers, masks, ointments, or filter fillers.

[0070] When the composition of the present invention is included in a quasi-drug for skin moisturizing purposes, the composition may be used as is, or used together with other quasi-drug ingredients, or used appropriately according to conventional methods. The amount of active ingredients mixed may be appropriately determined according to the purpose of use, and the quasi-drug composition according to the present invention may contain 0.01 to 20% by weight of the compound represented by chemical formula I or chemical formula II based on the total weight of the composition.

[0071] Furthermore, the present invention provides a method for treating allergic skin diseases or 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 aforementioned treatment method may, for example, involve the steps of a) measuring the amount of filaggrin expression in the patient, and b) determining that the patient needs to be administered the pharmaceutical composition if the amount of filaggrin expression decreases by 5.0% or more compared to a normal person, and administering the pharmaceutical composition to the patient. However, it is not limited to this, and the amount of the pharmaceutical composition administered to the patient and the administration cycle may differ depending on the amount by which filaggrin has decreased. For example, according to an embodiment of the present invention, it may be administered at a concentration of 0.5 to 2.5 μM once a day for 1 to 4 weeks, but it 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 illustrative of the present invention and that the scope of the present invention should not be construed as being limited by these examples.

[0074] [Materials, reagents, bacterial strains, equipment, etc.] - The human epidermal cell line (Normal Human Epidermal Keratinocyte, NHEK) is a human fetal transcutaneous cell line that was obtained from ATCC and used.

[0075] These cells were obtained in primary culture and were used to observe intracellular biochemical changes induced by ABT-751 or TN-16 under normal conditions, not disease conditions.

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

[0077] Furthermore, at 8-10 weeks of age, the skin thickness is approximately 0.4 mm, which is similar to human skin, offering advantages that make it useful for studying the pathogenesis of skin diseases and confirming biochemical changes within skin tissue.

[0078] [Test Example 1] 1.1. Measurement of filaggrin expression level using RNA extraction and RT-qPCR Human epidermal cell lines (NHEK) or mouse skin tissue coated with ABT-751, TN-16, or control samples 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 then the amount of filaggrin was measured quantitatively by 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 (Daehan Science Co.), then lysed using cell lysis buffer (RIPA buffer, Invitrogen), centrifuged using a centrifuge (Labogene), and the upper layer was transferred to a new tube and used as a protein sample.

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

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

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

[0084] After reacting the thin film with an ECL solution (Thermo Fisher), the reaction-completed protein was detected using a luminescence detector (Fusion Solo, Vilber).

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

[0086] [Example 1] Filaggrin expression level and cell differentiation in human epidermal cell lines treated with ABT-751 or TN-16 Human epidermal cell lines (NHEKs) in culture were treated with ABT-751 and TN-16, respectively, and filaggrin expression levels were measured to confirm changes in cell differentiation.

[0087] ABT-751 and TN-16 were treated with NHEK at concentrations of 0, 0.5, 1.0, and 2.5 μM, respectively. Filaggrin expression levels and cell differentiation levels were observed 24 hours after treatment.

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

[0089] From this, we confirmed that filaggrin expression levels increased in a concentration-dependent manner for ABT-751 and TN-16 treatment (see Figures 1a and 1b), and that the degree of cell differentiation increased significantly in the ABT-751-treated group compared to the untreated group (control group) (see Figure 2).

[0090] [Example 2] Filaggrin expression and cell differentiation in animal cells treated with ABT-751 or TN-16 Hairless hos:HR-1 mice (hereinafter referred to as HR-1 mice) were treated with the same amount of 0, 1, 2, and 4% formulations of ABT-751 and TN-16 once daily for 3 weeks.

[0091] After each application, the degree of skin water loss and the skin barrier index were measured using the method described in the test example above.

[0092] After two weeks of application, HR-1 mice were euthanized in a carbon dioxide chamber, and dorsal skin tissue was collected from each mouse.

[0093] 2-1 Measurement of filaggrin expression levels RNA and protein were extracted from skin tissue coated with ABT-751 or TN-16, respectively, using the method described in the above-mentioned test example, and filaggrin expression levels were measured. The results are shown in Figure 3.

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

[0095] 2-2. Measurement of skin water loss and skin barrier index Figure 4 shows the results of measuring skin water loss and skin barrier index after applying the control group (0% formulation ABT-751 or 0% formulation TN-16) and the 4% formulation ABT-751 or TN-16, respectively.

[0096] This confirms that application of the 4% formulation of ABT-751 or TN-16 reduces skin water loss at the application site and increases the skin barrier index in HR-1 mice (see Figures 4a-4d).

[0097] In particular, we confirmed that the decrease in skin water loss and the increase in the skin barrier index increased as the number of days of application progressed.

[0098] Although specific parts of the present invention have been described in detail above, it will be clear to those skilled in the art that such specific technologies are merely preferred embodiments and do not limit the scope of the present invention. Therefore, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims

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

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

3. The pharmaceutical composition for the prevention or treatment of an allergic skin disease or pruritus according to claim 1, wherein the allergic skin disease is atopic dermatitis.

4. A pharmaceutical composition for the prevention or treatment of allergic skin diseases or pruritus, as described in claim 1, which is administered by topical application to the skin.

5. The pharmaceutical composition for the prevention or treatment of allergic skin disease or pruritus according to claim 2, wherein the atopic dermatitis is caused by a decrease in filaggrin expression.

6. The pharmaceutical composition for the prevention or treatment of allergic skin diseases or pruritus according to claim 5, characterized in that the reduction in filaggrin expression is 5.0% or more compared to a normal person, and the pharmaceutical composition is administered to the patient.

7. A pharmaceutical composition for the prevention or treatment of allergic skin diseases or pruritus according to claim 1, wherein the dosage form is selected from the group consisting of ointments, creams, lotions, gels, topical solutions, pastes, liniments, and air rolls.

8. A cosmetic composition for the prevention or improvement of allergic skin diseases or pruritus, comprising the compound represented by the following chemical formula I or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical formula I] 【Chemistry 2】

9. A cosmetic composition for the prevention or improvement of allergic skin diseases or pruritus according to claim 8, which is any dosage form selected from the group consisting of a solution, topical ointment, cream, foam, nourishing lotion, softening lotion, pack, softening water, 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 skin moisturizing cosmetic composition containing a compound represented by the following chemical formula I or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical formula I] 【Transformation 3】

11. A quasi-drug composition for moisturizing the skin, containing as an active ingredient the compound represented by the following chemical formula I or a pharmaceutically acceptable salt thereof. [Chemical formula I] 【Chemistry 4】

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