Composition for preventing or treating atopic dermatitis or psoriasis comprising candesartan

Abstract

The present invention relates to a composition for preventing or treating atopic dermatitis or psoriasis, comprising candesartan. More specifically, the present invention provides a pharmaceutical composition, a cosmetic composition, and a functional health food composition for preventing or treating atopic dermatitis or psoriasis, comprising candesartan or a pharmaceutically / sitologically acceptable salt thereof as an active ingredient. The composition, according to the present invention, has excellent anti-inflammatory or anti-allergic activity by inhibiting the differentiation of T cells into helper T cell 17 (Th17) cells, thereby being capable of effectively preventing, alleviating, or treating atopic dermatitis or psoriasis.

Description

Composition for preventing or treating atopic dermatitis or psoriasis containing candesartan

[0001] The present invention relates to the use of candesartan for treating skin diseases, and more specifically, to a composition for preventing, improving or treating atopic dermatitis or psoriasis containing candesartan or a pharmaceutically / foodstuffally acceptable salt thereof as an active ingredient.

[0002] Angiotensin II receptor blockers (ARBs), or AT1 receptor antagonists, are drugs that regulate the renin-angiotensin system. They are primarily used to treat hypertension, but are also used to treat diabetic nephropathy and congestive heart failure. ARBs have been shown to suppress inflammatory responses in animal models of inflammatory diseases, including multiple sclerosis, autoimmune encephalomyelitis, and arthritis. Recently, the potential benefits of ARBs in systemic inflammation and allergic reactions have been studied. However, their efficacy in inflammatory skin diseases such as atopic dermatitis and psoriasis has not yet been demonstrated.

[0003] Atopic dermatitis, or psoriasis, is a chronic, allergic disease caused by genetic, environmental, and immunological factors. It is characterized by abnormalities in the stratum corneum, the outermost layer of the skin that acts as a protective barrier. It is a condition that worsens in dry climates. Atopic dermatitis and psoriasis have a global prevalence of approximately 10-20%, primarily affecting infants between one month and one year of age. While the condition typically improves somewhat by the age of three, it can recur depending on lifestyle factors and individual differences.

[0004] Their main symptoms include severe itching, dry skin, rash, oozing, crusting, and scaly skin (ichthyosis), often accompanied by chronic skin inflammation. Scratching, driven by itching, disrupts the skin barrier and leads to secondary infections, further exacerbating the inflammation. While these symptoms may temporarily improve, they can recur and worsen due to environmental and food irritants, and the condition can experience repeated cycles of exacerbation and relief.

[0005] Prescriptions for atopic dermatitis or psoriasis primarily include medications such as steroids, antihistamines, and antibiotics. While steroids (adrenal cortex hormones) are highly effective, primarily due to their anti-inflammatory and immunosuppressive properties, long-term use can lead to side effects such as skin weakening, systemic hormonal symptoms, and addiction.

[0006] Therefore, there is a need for a safe and effective treatment for atopic dermatitis or psoriatic dermatitis without side effects.

[0007] The purpose of the present invention is to provide a novel use of candesartan, an angiotensin II receptor blocker conventionally used as a treatment for hypertension, which has an excellent effect in improving or treating atopic dermatitis or psoriasis.

[0008] In order to achieve the above purpose, the present invention provides a pharmaceutical composition for preventing or treating atopic dermatitis or psoriasis, containing candesartan or a pharmaceutically acceptable salt thereof as an active ingredient.

[0009] The present invention provides a cosmetic composition for preventing or improving atopic dermatitis or psoriasis, containing candesartan or a pharmaceutically acceptable salt thereof as an active ingredient.

[0010] In addition, the present invention provides a health functional food composition for preventing or improving atopic dermatitis or psoriasis, containing candesartan or a food-related acceptable salt thereof as an active ingredient.

[0011] The composition according to the present invention has excellent anti-inflammatory or anti-allergic activity by inhibiting differentiation of T cells into helper T cell 17 (Th17) cells, and can be used as a pharmaceutical composition, cosmetic composition, and health functional food composition for preventing, improving, or treating atopic dermatitis or psoriasis.

[0012] The composition according to the present invention has been found to have an inhibitory activity on differentiation of T cells into Th17 cells, and can be further utilized as a treatment for diseases related thereto.

[0013] Figure 1. Effect of angiotensin II receptor blocker (ARB) on atopic dermatitis-like response in ear tissue. (A) is a schematic diagram showing the experimental plan, (B) is a macroscopic observation image of the ear on day 49 of the experiment, (C) is a hematoxylin and eosin (H&E) staining image of mouse ear skin tissue on day 49, (D) is a graph of ear skin thickness measurement in tissue sections, and the graph represents the mean ± standard error of the mean (SEM) of the mean value (n = 5). (***P < 0.001 vs. vehicle-treated group, ###P < 0.001 vs. CDNB-treated group, $$$P < 0.001 vs. telmisartan-treated group)

[0014] Figure 2. Effects of ARB on mast cell accumulation and inflammatory cytokine levels in the ear. (A) Toluidine blue O (TBO) staining of ear skin samples on day 49, (B) mast cell counts in different tissue sections, (C) expression levels of interleukin (IL)-4, (D) IL-13, (E) interferon (IFN)-γ, and (F) IL-17A. Data are expressed as mean ± standard error of the mean (SEM) (n = 5) (***P < 0.001, **P < 0.01 vs. vehicle-treated group; ###P < 0.001, ##P < 0.01 vs. CDNB-treated group; $$$P < 0.001, $$P < 0.01 vs. telmisartan-treated group).

[0015] Figure 3 shows the effect of ARB on the size of lymph nodes and the levels of inflammatory cytokines in lymph nodes. (A) The photograph of the isolated cervical lymph nodes on day 49, (B) The weight of the isolated lymph nodes, (C) The expression levels of IL-4, (D) IL-13, (E) IL-17A, and (F) IFN-γ are shown. Data are expressed as the mean ± standard error of the mean (SEM) (n = 5) (***P < 0.001 vs. vehicle treatment group; ###P < 0.001, ##P < 0.01 vs. CDNB treatment group; $$$P < 0.001, $$P < 0.01 vs. telmisartan treatment group).

[0016] Figure 4 shows the effect of ARB on the differentiation of naive T cells into T helper (Th)-17 cells. (A) is the result of flow cytometry analysis, and (B) is the result of CD4 + IL-17A +For histograms of cell populations, the Gaussian distribution assumption of the data was made using the Kolmogorov-Smirnov (KS) test. Data are presented as mean ± standard error of the mean (SEM) (n = 5) (***P < 0.001 vs. vehicle-treated group; ###P < 0.001, #P < 0.05 vs. Th17 differentiation medium-treated group).

[0017] Figure 5 shows the effect of ARB on psoriasis-like skin reactions. (A) is a schematic diagram showing the experimental plan, (B) is a macroscopic observation image of the skin of the back of a mouse 6 days after treatment, and (C) is a graph of thickness, erythema, scaling, and total psoriasis area and severity index (PASI) scores on day 7. The data were analyzed by two-way analysis of variance with Bonferroni multiple comparison post-hoc test, and the data are expressed as mean ± standard error of the mean (SEM) (n = 5) (***P < 0.001 vs. vehicle treatment group; ###P < 0.001, ##P < 0.01, #P < 0.05 vs. imiquimod treatment group).

[0018] Figure 6 shows the effect of ARB on histological changes in psoriatic skin. (A) is an H&E staining image of back skin, in which the epidermal ridges were elongated and clubbed, as well as moderate to severe dermal lymphocytic infiltration, in the imiquimod-treated group. (B) is a Ki-67 staining image, with red arrows indicating Ki-67-positive cells. (C) is an epidermal thickness, and (D) is a Ki-67 staining image. + Data are presented as mean ± standard error of the mean (SEM) in histograms of cell counts (n = 5) (***P < 0.001 vs. vehicle-treated group; ###P < 0.001, ##P < 0.01 vs. imiquimod-treated group).

[0019] Figure 7 shows the effects of ARB on Th17 and Th1-related cytokine levels in the skin. The results of qRT-PCR analysis of the mRNA expression levels of cytokines related to Th17 (IL-17A, IL-23, and IL-22) and Th1 (IFN-γ, tumor necrosis factor [TNF]-α, and IL-1β) in skin tissues isolated from imiquimod-induced and ARB-treated mice are shown. (A) IL-17A, (B) IL-23, (C) IL-22, (D) IFN-γ, (E) TNF-α, and (F) IL-1β. The relative mRNA levels of cytokines were quantified by calculating the ratio of the levels to the GAPDH transcript level. Data are expressed as mean ± standard error of the mean (SEM) (n = 5) (***P < 0.001, **P < 0.01 vs. vehicle-treated group; ###P < 0.001, ##P < 0.01, #P < 0.05 vs. imiquimod-treated group).

[0020] Figure 8 shows the size of lymph nodes and spleen and CD4 + IL-17A + To confirm the effect of ARB on T cell population, (A) evaluated the morphological changes of draining lymph nodes, (B) the weight of lymph nodes, and (C) CD4 in lymph nodes. + IL-17A + (D) shows the morphological changes of the spleen, (E) shows the measured weight of the spleen, and (F) shows the CD4 count in the spleen. + IL-17A + The percentage of T cells is shown. The Gaussian distribution assumption of the data was confirmed using the KS test, and the data are expressed as the mean ± standard error of the mean (SEM) (n = 5) (***P < 0.001 vs. vehicle-treated group; ###P < 0.001, ##P < 0.01, #P < 0.05 vs. imiquimod-treated group).

[0021] Figure 9 shows the effect of ARB on Th17 and Th1-related cytokine levels in lymph nodes. The levels of (A) IL-17A, (B) IL-23, (C) IL-22, (D) IFN-γ, (E) TNF-α, and (F) IL-1β are shown. The relative mRNA levels of cytokines were quantified by calculating the ratio of the levels to the GAPDH transcript levels. Data are expressed as the mean ± standard error of the mean (SEM) (n = 5) (***P < 0.001, **P < 0.01, *P < 0.05 vs. vehicle-treated group; ###P < 0.001, ##P < 0.01, #P < 0.05 vs. imiquimod-treated group).

[0022] Figure 10 is a schematic diagram showing the therapeutic effects of candesartan and telmisartan on atopic dermatitis and psoriasis. Candesartan suppresses atopic dermatitis and psoriasis by inhibiting the differentiation of naive T cells into Th17 cells, thereby reducing IL-17 production and simultaneously suppressing Th1 / Th2 / Th22 cytokines. Telmisartan suppresses atopic dermatitis and psoriasis by activating PPAR-γ, thereby inhibiting NF-kB activation, and consequently suppressing the production of inflammatory cytokines.

[0023] Hereinafter, the present invention will be described in detail.

[0024]

[0025] The present inventors completed the present invention by confirming the in vivo anti-inflammatory effect of angiotensin II receptor blocker (ARB) on skin diseases, and by confirming the effects of candesartan and telmisartan on atopic dermatitis induced by 1-chloro-2,4-dinitrobenzene (CDNB) and psoriasis-like skin models induced by imiquimod.

[0026]

[0027] As used herein, "prevention" refers to any action that inhibits or delays the onset of atopic dermatitis, psoriasis, or at least one symptom thereof by administering a pharmaceutical composition, cosmetic composition, or health functional food composition according to the present invention. It also includes treatment of a subject suffering from the disease to prevent or mitigate recurrence.

[0028] In this specification, “treatment” means any act of improving or beneficially altering the symptoms of atopic dermatitis, psoriasis, or at least one symptom thereof, such as alleviating, reducing, or eliminating the symptoms, by administering a pharmaceutical composition according to the present invention.

[0029] In this specification, “improvement” means any act of alleviating, reducing, or eliminating the symptoms of atopic dermatitis, psoriasis, or at least one symptom thereof by administering a cosmetic composition or health functional food composition according to the present invention, or of beneficially altering the symptoms thereof.

[0030]

[0031] The present invention provides a pharmaceutical composition for preventing or treating atopic dermatitis or psoriasis, containing candesartan or a pharmaceutically acceptable salt thereof as an active ingredient.

[0032] In this specification, “Candesartan” is a compound represented by the following chemical formula 1, which is an angiotensin II receptor blocker (ARB) mainly used for the treatment of hypertension and heart failure.

[0033] <Chemical Formula 1>

[0034]

[0035] Preferably, the candesartan may be contained and act in the form of candesartan cilexetil represented by the following chemical formula 2, but is not limited thereto.

[0036] <Chemical Formula 2>

[0037]

[0038] The above candesartan can be synthesized by a method well known in the art, and a commercially available one can be selected and used, but the method or material is not particularly limited.

[0039] The above candesartan can be used in the form of a pharmaceutically or food-wise acceptable salt within the range of efficacy.

[0040] As used herein, “pharmaceutically or food-wise acceptable” means a salt that is non-toxic to cells or humans exposed to the composition and has a safety and efficacy profile suitable for administration to humans.

[0041] The above salt may be used in the form of either a basic salt or an acid salt that is pharmaceutically or food-wise acceptable. The basic salt may be used in the form of either an organic basic salt or an inorganic basic salt, and may be selected from the group consisting of sodium salt, potassium salt, calcium salt, lithium salt, magnesium salt, cesium salt, aminium salt, ammonium salt, triethylaminium salt, and pyridinium salt.

[0042] Acid salts are useful as acid addition salts formed by free acids. Inorganic acids and organic acids can be used as free acids, and inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, sulfurous acid, phosphoric acid, diphosphoric acid, nitric acid, etc., and organic acids include citric acid, acetic acid, maleic acid, malic acid, fumaric acid, gluconic acid, methanesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, oxalic acid, malonic acid, glutaric acid, acetic acid, glycolic acid, succinic acid, tartaric acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid, citric acid, aspartic acid, stearic acid, etc., but are not limited thereto, and all salts formed using various inorganic acids and organic acids commonly used in the art can be included.

[0043] In addition, the above candesartan may include not only the above salts, but also all salts, hydrates, solvates, derivatives, etc. that can be prepared by conventional methods. The addition salt may be prepared by conventional methods, and may be prepared by dissolving in a water-miscible organic solvent such as acetone, methanol, ethanol, or acetonitrile, adding an excess amount of organic base, or adding an aqueous base solution of an inorganic base, and then precipitating or crystallizing. Alternatively, the addition salt may be obtained by evaporating the solvent or the excess base from the mixture and then drying, or the precipitated salt may be prepared by suction filtration.

[0044]

[0045] The composition according to the present invention exhibits anti-allergic or anti-inflammatory activity by inhibiting the differentiation of T cells into helper T cell 17 (Th17) cells, thereby improving or suppressing atopic dermatitis, psoriasis, or their symptoms. By inhibiting differentiation into Th17 cells, IL-17 production can be reduced, and further, the production of Th1, Th2, Th22, or Th17-related cytokines can be suppressed.

[0046] According to one experimental example of the present invention, it can be confirmed that candesartan reduces the mRNA expression levels of IL-4, IL-13, IFN-γ, or IL-17A, which are Th1, Th2, or Th17-related cytokines associated with atopic dermatitis. In addition, it can be confirmed that candesartan reduces the mRNA expression levels of IL-17A, IL-23, IL-22, IFN-γ, TNF-α, or IL-1β, which are Th1, Th22, or Th17-related cytokines associated with psoriasis. In addition, the composition can inhibit the infiltration of mast cells and inhibit the proliferation of Ki-67 positive cells.

[0047] According to one experimental example of the present invention, it can be confirmed that candesartan according to the present invention has a superior therapeutic effect on atopic dermatitis or psoriasis than telmisartan, which is another angiotensin II receptor blocker. In this case, unlike telmisartan, which acts on atopic dermatitis or psoriasis through the activation of PPARγ (peroxisome proliferator-activated receptor), candesartan has a different mechanism of action due to its effect by inhibiting differentiation into Th17 cells.

[0048] That is, even angiotensin II receptor blockers may have different mechanisms of action for anti-allergic or anti-inflammatory activity, and the treatment of atopic dermatitis or psoriasis through inhibition of differentiation of Th17 cells by candesartan is the first to be elucidated in the present invention.

[0049]

[0050] In this specification, "pharmaceutical composition" means a composition administered for a specific purpose, and for the purposes of the present invention, it means administered to prevent or treat atopic dermatitis, psoriasis, or at least one symptom thereof.

[0051] The pharmaceutical composition according to the present invention can be prepared according to conventional methods in the pharmaceutical field. The pharmaceutical composition can be combined with an appropriate pharmaceutically acceptable carrier depending on the dosage form, and, if necessary, can be prepared by further including excipients, diluents, dispersants, emulsifiers, buffers, stabilizers, binders, disintegrants, solvents, etc. The appropriate carrier, etc., can be selected differently depending on the dosage form and dosage form as long as it does not inhibit the activity and properties of candesartan or a pharmaceutically acceptable salt thereof according to the present invention.

[0052] The pharmaceutical composition according to the present invention can be applied in any dosage form, and more specifically, it can be formulated and used as an oral dosage form, an external preparation, a suppository, and a parenteral dosage form of a sterile injection solution according to a conventional method.

[0053] Among the oral dosage forms, the solid dosage form may be in the form of tablets, pills, powders, granules, capsules, etc., and may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be included. In addition, in the case of a capsule dosage form, in addition to the above-mentioned substances, a liquid carrier such as fatty oil may be further included.

[0054] Among the above oral dosage forms, liquid dosage forms include suspensions, solutions, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.

[0055] The above parenteral formulations may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include witepsol, macrogol, Tween 61, cacao butter, laurin, glycerogelatin, and the like. Without limitation, any suitable formulation known in the art may be used.

[0056]

[0057] In the pharmaceutical composition according to the present invention, the pharmaceutical composition can be administered in a pharmaceutically effective amount.

[0058] As used herein, “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing adverse effects.

[0059] The effective dosage level of the pharmaceutical composition may vary depending on the intended use, the patient's age, sex, weight, and health condition, the type and severity of the disease, the activity and sensitivity of the drug, the method of administration, the time of administration, the route of administration, and the excretion rate, the duration of treatment, the drugs used in combination or concurrently, and other factors well known in the medical field. For example, although not fixed, it may generally be administered once or several times daily at a dosage of 0.001 to 1000 mg / kg, preferably 0.01 to 100 mg / kg. The above dosage does not limit the scope of the present invention in any way.

[0060]

[0061] The pharmaceutical composition according to the present invention can be administered to any animal that can develop atopic dermatitis or psoriasis, and the animal can include, for example, humans and primates, as well as livestock such as cows, pigs, horses, and dogs.

[0062] The pharmaceutical composition according to the present invention can be administered via an appropriate route of administration depending on the formulation form, and can be administered via various routes, either oral or parenteral, as long as it can reach the target tissue. The method of administration is not particularly limited, and can be administered by conventional methods such as oral, rectal, intravenous, intramuscular, or skin application, respiratory inhalation, intrauterine epidural, or intracerebroventricular injection.

[0063] The pharmaceutical composition according to the present invention can be used alone for the prevention or treatment of atopic dermatitis or psoriasis, or can be used in combination with surgery or other drug treatments.

[0064]

[0065] The present invention provides a cosmetic composition for preventing or improving atopic dermatitis or psoriasis, containing candesartan or a pharmaceutically acceptable salt thereof as an active ingredient.

[0066] The above composition has an excellent improvement effect on atopic dermatitis or psoriasis by inhibiting the differentiation of T cells into helper T cell 17 (Th17) cells, and thus can be used as a cosmetic composition for preventing or improving atopic dermatitis or psoriasis.

[0067] In this specification, "cosmetics" may include functional cosmetics having effects of skin protection, skin moisturizing, and improving atopic dermatitis or psoriasis dermatitis, and the functional cosmetics, unlike general cosmetics, have specialized functionality with emphasized physiologically active effects and effects, and mean cosmetics with emphasized specific effects and effects such as skin protection, skin moisturizing, and atopic skin improvement.

[0068]

[0069] The cosmetic composition according to the present invention may further include one or more ingredients from the list of cosmetic raw materials registered with the Ministry of Food and Drug Safety and the ICID (International Cosmetic Ingredient Dictionary). For example, the cosmetic composition may further include one or more auxiliary agents commonly used in the cosmetic field, such as organic solvents, solubilizers, thickeners, gelling agents, softeners, antioxidants, suspending agents, stabilizers, fragrances, surfactants, emulsifiers, fillers, metal ion sequestrants, preservatives, vitamins, blocking agents, humectants, dyes and pigments, hydrophilic or lipophilic active agents, or any other ingredients commonly used in cosmetics.

[0070] The above vitamins may include water-soluble or oil-soluble vitamins, and the water-soluble vitamins are water-soluble vitamins that can be incorporated into cosmetics, and preferably include vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinamide, folic acid, vitamin C, vitamin H, etc. In addition, their salts (thiamine hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbate-2-phosphate, magnesium ascorbate-2-phosphate, etc.) may also be included, and the water-soluble vitamins may be obtained by a conventional method such as a microbial transformation method, a purification method from a microbial culture, an enzymatic method, or a chemical synthesis method.

[0071]

[0072] The cosmetic composition according to the present invention may be prepared in any formulation commonly manufactured in the technical field to which the present invention pertains. For example, the cosmetic composition may be formulated as a toner, emulsion, lotion, cream, paste, gel, solution, suspension, oil, wax, pack, powder, foundation, spray, surfactant-containing cleanser, etc., but is not limited thereto.

[0073] More specifically, it can be manufactured in the form of a flexible toner, a nourishing toner, an astringent toner, a nourishing cream, a massage cream, a milk lotion, a powder, an essence, an eye cream, a sun lotion, a sunscreen, a makeup primer, a makeup base, a BB cream, a powder foundation, an emulsion foundation, a cleansing cream, a cleansing foam, a cleansing water, a soap, a pack, a stick product, a balm type product, a spray, or a powder.

[0074] When the cosmetic composition according to the present invention is in the form of a cream or gel, it may further include animal oil, vegetable oil, wax, paraffin, starch, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide as a carrier component.

[0075] When the above cosmetic composition is in the form of a solution or emulsion, it may further include a solvent, solvating agent or emulsifying agent, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, propylene glycol, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

[0076] If the above cosmetic composition is in the form of a suspension formulation, it may further include a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth as a carrier component.

[0077] If the above cosmetic composition is in a powder or spray form, it may further include lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder as a carrier component, and particularly if it is in a spray form, it may further include a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether.

[0078] When the above cosmetic composition is a surfactant-containing cleansing formulation, it may further include, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyl taurate, a sarcosinate, a fatty acid amide ether sulfate, an alkylamidobetaine, an aliphatic alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a linolenic derivative, or an ethoxylated glycerol fatty acid ester.

[0079]

[0080] The cosmetic composition according to the present invention may be applied alone or in combination, or may be applied in combination with other cosmetic compositions other than those of the present invention. Furthermore, the cosmetic composition according to the present invention may be used according to conventional methods, and the frequency of application may vary depending on the user's skin condition or preference.

[0081]

[0082] In addition, the present invention provides a health functional food composition for preventing or improving atopic dermatitis or psoriasis, containing candesartan or a food-related acceptable salt thereof as an active ingredient.

[0083] The above composition has an excellent improvement effect on atopic dermatitis or psoriasis by inhibiting the differentiation of T cells into helper T cell 17 (Th17) cells, and thus can be used as a health functional food composition for preventing or improving atopic dermatitis or psoriasis.

[0084] In this specification, "health functional food" includes food manufactured and processed using raw materials or ingredients with functionality useful to the human body according to Act No. 6727 on Health Functional Foods, and means a food with high medical or healthcare effects that is processed to efficiently exhibit bioregulatory functions such as prevention of atopic dermatitis or psoriasis, biodefense, immunity, and recovery for the purpose of the present invention in addition to nutritional supply.

[0085]

[0086] In the health functional food composition according to the present invention, the health functional food may be manufactured in the form of powder, granules, tablets, capsules, syrup, or beverage, etc., for the purpose of preventing or improving atopic dermatitis or psoriasis. There is no limitation on the form that the health functional food may take, and it may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods.

[0087] In the health functional food composition according to the present invention, the health functional food may include all foods in the conventional sense. For example, the health functional food may include beverages and various drinks, fruits and processed foods thereof (canned fruits, jams, etc.), fish, meats and processed foods thereof (ham, bacon, etc.), breads and noodles, cookies and snacks, dairy products (butter, cheese, etc.), etc., and may include all functional foods in the conventional sense. In addition, foods used as animal feed may also be included.

[0088]

[0089] The health functional food composition according to the present invention can be manufactured by further including food additives (food additives) that are commonly used in the art and are food-relatedly acceptable and other appropriate auxiliary ingredients. Unless otherwise specified, the suitability as a food additive can be determined by the specifications and standards for the relevant item in accordance with the general provisions and general test methods of the Food Additives Codex approved by the Ministry of Food and Drug Safety. Items listed in the above 'Food Additives Codex' include, for example, chemical synthetics such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, sucrose pigment, and guar gum; and mixed preparations such as sodium L-glutamate preparations, alkaline agents for noodles, preservative preparations, and tar color preparations.

[0090] The above other auxiliary ingredients may additionally contain, for example, flavoring agents, natural carbohydrates, sweeteners, vitamins, electrolytes, coloring agents, pectic acid, alginic acid, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonating agents, etc. In particular, as the natural carbohydrates, monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol can be used, and as the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame can be used.

[0091]

[0092] The effective dose of candesartan contained in the health functional food according to the present invention can be appropriately adjusted depending on the purpose of use, such as prevention or improvement of atopic dermatitis or psoriasis.

[0093] The above health functional food composition has the advantage of not having side effects that may occur with long-term use of general medicines as it is made from food, and is highly portable, so it can be taken as a supplement for preventing or improving atopic dermatitis or psoriasis.

[0094] Hereinafter, to aid understanding of the present invention, examples will be given in detail. However, the following examples are intended only to illustrate the scope of the present invention and are not intended to limit its scope. These examples are provided to more fully explain the present invention to those of average skill in the art.

[0095]

[0096] <Experimental Method>

[0097] 1. Materials

[0098] Candesartan cilexetil (MW 610.66, SML0245, ≥98% high-performance liquid chromatography [HPLC], Pubchem ID 329825255), telmisartan (MW 514.62, T8949, ≥98% HPLC, Pubchem ID 329826889), GW9662 (MW 495.57, G5668, ≥98% HPLC, Pubchem ID 24278789), olive oil, 1-chloro-2,4-dinitrobenzene (CDNB), and other materials were purchased from Sigma-Aldrich (St. Louis, MO, USA).

[0099]

[0100] 2. Animals

[0101] Male BALB / c mice (7 weeks old, n = 5 per group) were purchased from Daehan Biolink Co., Ltd. (Seoul, Korea) and maintained in the Kyung Hee University Laboratory Animal Facility. All animals were housed at 23 ± 2°C and 60 ± 5% humidity under a 12-h light / dark cycle and were provided with standard laboratory chow and water ad libitum. The Animal Care and Use Committee of Kyung Hee University reviewed and approved the animal experiment protocol for this experiment (Approval No. KHSASP-20-372, KHSASP-22-064).

[0102]

[0103] 3. Induction of atopic dermatitis-like reactions in BALB / c mice

[0104] Atopic dermatitis was induced in mice by topical application of CDNB prepared in a 3:1 mixture of acetone and olive oil. After 1 week of acclimation, mice with CDNB-induced atopic dermatitis were randomly divided into the following seven groups (n = 5 per group):

[0105] vehicle (3:1 mixture of acetone and olive oil)-, CDNB-, candesartan / CDNB-, telmisartan / CDNB-, GW9662 / CDNB-, GW9662 / candesartan / CDNB-, and GW9662 / telmisartan / CDNB-treated groups.

[0106] Briefly, on day 0, the abdominal fur of mice was removed, and 1% CDNB solution (300 μL) was applied to the abdominal skin as an immunogen to sensitize them. Starting on day 7, atopic dermatitis-like skin lesions were induced by applying 0.3% CDNB (200 μL) to the ears every other day. Candesartan (10 mg / kg body weight), telmisartan (10 mg / kg body weight), and GW9662 (1 mg / kg body weight) were administered intraperitoneally 30 minutes before CDNB induction from day 19 until the end of the experiment. All mice were sacrificed on day 49.

[0107]

[0108] 4. Induction of psoriasis-like response in BALB / c mice

[0109] Eight-week-old male BALB / c mice were randomly divided into four groups (n = 5 per group):

[0110] vehicle-, imiquimod-, candesartan / imiquimod-, telmisartan / imiquimod-treated groups

[0111] On day 0, the dorsal hair of the mice was shaved. From day 1, 62.5 mg of 5% imiquimod cream (Aldara Cream, Dong-A ST) was applied daily for 6 days to induce psoriasis-like dermatitis. The vehicle-treated group was applied with vehicle cream (Vaseline). Candesartan and telmisartan (10 mg / kg body weight each) were administered intraperitoneally 30 minutes before applying imiquimod cream for 6 days. The mice were sacrificed on day 7.

[0112] During the experimental period, skin inflammation was assessed using the Psoriasis Aging and Severity Index (PASI), which included erythema, scaling, and skin thickness, scored from 0 to 4 (0, none; 1, mild; 2, moderate; 3, severe; 4, very severe). The total PASI score was calculated by adding the severity scores (0 to 12). Ear thickness was measured using H&E-stained micrographs. The average value was calculated from five measurements per mouse.

[0113]

[0114] 5. Histology and immunohistochemistry

[0115] For histological evaluation of skin inflammation, skin tissues from the left ear and back were fixed in 10% formalin. The skin tissues were dehydrated in a 30% sucrose solution at 4°C for 2 days, embedded in optimal cutting temperature compound, and sectioned at 8 μm thickness. The tissue sections were stained with hematoxylin and eosin (H&E) or toluidine blue O (cat. T3260; Sigma-Aldrich, St. Louis, MO, USA) to identify skin hypertrophy and mast cells. Ear tissues from five mice in each group were examined.

[0116] For immunohistochemical staining of Ki-67, tissue sections were washed with phosphate-buffered saline (PBS-T) containing 0.5% Tween-20. The sections were then blocked with PBS-T containing 5% bovine serum albumin for 30 minutes at room temperature. The sections were labeled with Ki-67 recombinant rabbit monoclonal antibody (MA5-14520, Invitrogen) for 1 hour at room temperature. The VECTASTAIN Elite ABC Kit (PK-6101, Vector Laboratories) was used for staining. The tissue slides were incubated with ImmPACT DAB substrate (SK-4105; Vector Laboratories) for 10 minutes at room temperature to visualize the peroxidase reaction products. Finally, the slides were counterstained with hematoxylin.

[0117]

[0118] 6. Quantitative real-time polymerase chain reaction (qRT-PCR)

[0119] The expression levels of inflammatory markers in mouse lymph nodes and skin were determined by reverse transcription (RT)-PCR. First-strand cDNA was synthesized from total RNA and isolated using TRIzol reagent (Invitrogen, Waltham, MA, USA). Total RNA was isolated from lymph node and skin tissues, and mRNA was transcribed into cDNA using Moloney Murine Leukemia Virus Reverse Transcriptase (Promega, Madison, WI, USA). Quantitative PCR was performed using Thunderbird Next SYBR qPCR Mix (Toyobo, Osaka, Japan) and a CFX Connect Real-Time System (Bio-Rad, Hercules, CA, USA). Thermal cycling conditions were as follows: 1 cycle at 95°C for 4 min, 40 cycles at 95°C for 30 s and 57°C for 30 s, and 1 cycle at 95°C for 30 s. The expression of each gene was normalized to that of GAPDH (glyceraldehyde 3-phosphate dehydrogenase). The data obtained were analyzed using the 2-ΔΔCt method in CFX Maestro Software. Primer sequences are listed in Table 1.

[0120] mouse Primer sequenceIl-4forward5'-CCAAGGTGCTTCGCATATTT-3'reverse5'-ATCGAAAAGCCCGAAAGAGT-3'Il-13forward5'-CAGCATGGTATGGAGTGTGG-3'reverse5'-AGGCCATGCAATATCCTCTG-3'Il-17Aforward5 '-AGCTGGACCACCACATGAAT-3'reverse5'-AGCATCTTCTCGACCCTGAA-3'Il-22forward5'-CCGAGGAGTCAGTGCTAAGG-3'reverse5'-CATGTAGGGGCTGGAACCTGT-3'Il-23forward5'-GACCCACAAGGACTCAA GGA-3'reverse5'-CATGGGGCTATCAGGGAGTA-3'Il-1βforward5'-CAGGCAGGCAGTATCACTCA-3'reverse5'-TGTCCTCATCCTGGAAGGTC-3'Ifn-γforward5'-CACGGCACAGTCATTGAAAG-3'reverse5'GTCA CCATCCTTTTGCCAGT-3'Tnf-αforward5'-ACGGCATGGATCTCAAAGAC-3'reverse5'-AGATAGCAAATCGGCTGACG-3'Gapdhforward5'-AACTTTGGCATTGTGGAAGG-3'reverse5'-GGATGCAGGGATGATGTTCT-3'

[0121]

[0122] 7. T helper (Th)-17 differentiation

[0123] Naive CD4 + T cells are magnetically labeled with beads (Naive CD4 + T Cell Isolation Kit; Miltenyi Biotec) was used to isolate from mouse spleen cells and differentiate into Th17 cells using Mouse Th17 Cell Differentiation Kit (Cat. CDK017; R&D systems). Naive CD4 +T cells were cultured in Th17 differentiation medium (X-VIVO 15, Lonza) for 3 days in 12-well plates coated with anti-mouse CD3. Fresh Th17 differentiation medium was added on day 3, and the cells were cultured for two more days. On day 5, cells were harvested, and Th17 differentiation was analyzed using flow cytometry. Candesartan and telmisartan (at concentrations of 5 and 10 μM, respectively) were added to the Th17 differentiation medium to determine their effects.

[0124]

[0125] 8. Flow cytometry

[0126] To identify Th17 cell populations, single cells isolated from lymph nodes and spleens were stained with fluorescein isothiocyanate-labeled anti-CD4 rat antibody (cat. 11-0041-82; eBioscience) for 15 min at 4°C. Cells were fixed for 1 h at room temperature using IC fixation buffer (cat. 00-8222-49; eBioscience). After fixation, cells were stained with eFluor 660-labeled rat anti-IL-17A (cat. 50-7177-82; eBioscience) for 1 h at room temperature using permeabilization buffer (cat. 88-8824-00; eBioscience). Cells were analyzed using a CytoFLEX flow cytometer (Beckman Coulter). 10,000 events were collected for Th17 analysis. Single cells were set as the first gate to remove debris in the forward scatter (FSC) / side scatter (SCC) plot. CD4 + IL-17A + The cells were identified as Th17 cells.

[0127]

[0128] 9. Normality and Statistical Analysis

[0129] Normality and statistical tests were performed using GraphPad Prism software (GraphPad Software, Inc., La Jolla, CA, USA). Continuous data are expressed as the mean ± standard error of the mean (SEM) for five animal measurements. The Kolmogorov-Smirnov (KS) test was performed to assess whether the data met the assumption of normality. All tested data passed the normality test. Differences between treatment groups were analyzed using analysis of variance (ANOVA) with Tukey's multiple comparisons post-hoc test. PASI scores were analyzed using a two-way ANOVA with Bonferroni's post-hoc test. Statistical significance was defined as p<0.05, and * indicates a significant difference compared to the vehicle-treated group. # indicates comparison with the CDNB- or imiquimod-treated group, and $ indicates comparison with the telmisartan-treated group.

[0130]

[0131] <Experimental Results>

[0132] 1. Confirmation of inhibition of atopic dermatitis-like reactions in ear tissue following angiotensin II receptor blocker (ARB) treatment.

[0133] The potential effects of candesartan and telmisartan on inflammatory skin diseases were investigated using a CDNB-induced mouse atopic dermatitis-like model in BALB / c mice. Several ARBs, including telmisartan, exert their anti-inflammatory effects by directly binding to and activating PPARγ. Because GW9662 is a selective PPARγ inhibitor, the effects of PPARγ activation were examined using a GW9662-treated mouse model in this experiment.

[0134] As a result, as shown in Fig. 1(B), CDNB-treated mice exhibited severe atopic dermatitis-like symptoms, such as edema, erythema, and wounds, which were suppressed by administration of candesartan or telmisartan. Although GW9662 treatment alone did not affect CDNB-induced atopic dermatitis, it inhibited the inhibitory effect of telmisartan on CDNB-induced skin lesions, demonstrating that PPARγ activation is the main mechanism by which telmisartan inhibits dermatitis. On the other hand, in the candesartan-treated group, GW9662 did not inhibit the inhibitory effect of candesartan on inflammatory skin lesions, indicating that PPARγ is not a target of candesartan.

[0135] Referring to Figure 1(C), the aforementioned macroscopic observations were consistent with the histological examination of ear skin tissue. H&E-stained sections showed epidermal proliferation and inflammation in the CDNB-treated group, and CDNB-induced hyperplasia was improved in both ARB-treated groups. Consistent with the macroscopic observations, GW9662 treatment inhibited the inhibitory effect of telmisartan, but not that of candesartan. Many inflammatory immune cells were observed in the ear skin of the CDNB-treated group, resulting in edema and epidermal hyperplasia, but the CDNB-induced increase in immune cells was inhibited by both ARBs, and GW9662 treatment inhibited the telmisartan-induced inhibition.

[0136] Referring to Figure 1(D), ear thickness was significantly increased by 235.87% induced by CDNB, which was significantly suppressed by both ARBs (candesartan by 68.52% and telmisartan by 57.28%). GW9662 reversed the inhibitory effect of telmisartan on proliferation, but not that of candesartan.

[0137]

[0138] 2. Confirmation of reduced mast cell infiltration into ear tissue following ARB treatment in a mouse model.

[0139] Mast cells contribute to the neuroinflammatory inflammation that causes pain and itching in atopic dermatitis. Therefore, ear tissue was stained with TBO to analyze mast cells.

[0140] Referring to Figure 2(A), mast cells were indicated by purple dots and accumulated in the epidermis of ear tissue in the CDNB-treated group. Both ARBs suppressed the increased mast cell count, and GW9662 treatment reversed the inhibitory effect of telmisartan but not that of candesartan.

[0141] Referring to Fig. 2(B), the number of mast cells in the ear tissue sections of the CDNB group increased by 563.24% compared to the vehicle-treated control group, but administration of candesartan or telmisartan significantly suppressed the number of mast cells by 71.69% and 61.42%, respectively. Treatment with GW9662 reversed the inhibitory effect of telmisartan on mast cell infiltration, but did not reverse the inhibitory effect of candesartan.

[0142]

[0143] 3. Confirmation of inhibition of increase in Th1, Th2, and Th17-related cytokine levels in ear tissue following ARB treatment

[0144] In the CDNB-induced atopic dermatitis model, excessive Th2 responses, as well as Th1 and Th17 responses, are involved in the pathogenesis of atopic dermatitis. Changes in Th2, Th1, and Th17 responses were measured by quantifying the expression levels of Th2- (interleukin [IL]-4 and IL-13), Th1- (interferon [IFN]-γ), and Th17-associated (IL-17A) cytokines in ear tissue.

[0145] Referring to Figures 2(C) to 2(F), it was confirmed that the mRNA expression levels of the four cytokines were significantly increased by CDNB induction, and both ARBs significantly suppressed the increased expression levels of IL-4, IL-13, IFN-γ, and IL-17A. The inhibitory effect of telmisartan on the expression levels of the four cytokines was reversed by GW9662, but the inhibitory effect of candesartan was not reversed.

[0146]

[0147] 4. Confirmation of suppression of atopic response in lymph nodes following ARB treatment

[0148] Cervical lymph nodes are the lymphoid organs closest to the ear and regulate the immune response to CDNB in ​​the ear.

[0149] Referring to Figure 3(A), significant lymph node enlargement due to lymphocyte proliferation was observed in the CDNB-treated group, which was suppressed by both ARBs. GW9662 treatment reversed the inhibitory effect of telmisartan but not that of candesartan.

[0150] Referring to Figure 3(B), the weight of isolated lymph nodes increased by up to 529.87% in the CDNB-treated group. Candesartan and telmisartan significantly suppressed the increase in lymph node weight by 51.32% and 39.58%, respectively. GW9662 reversed the inhibitory effect of telmisartan on increased lymph node weight, but did not reverse the inhibitory effect of candesartan.

[0151]

[0152] 5. Confirmation of inhibition of increase in Th1, Th2, and Th17-related cytokine levels in lymph nodes following ARB treatment.

[0153] Inflammatory cytokine levels were assessed by quantifying mRNA levels of IL-4, IL-13, IFN-γ, and IL-17A in lymph nodes isolated from mice.

[0154] Referring to Figures 3(C) to 3(F), CDNB treatment significantly increased the mRNA expression levels of four cytokines in the lymph nodes. While both ARBs suppressed the increase in inflammatory cytokine levels, GW9662 appeared to inhibit only the inhibitory effects of telmisartan, but not candesartan, on Th2, Th1, and Th17 responses.

[0155]

[0156] 6. Confirmation of inhibition of differentiation of T lymphocytes into Th17 cells following ARB treatment

[0157] To identify fewer Th17 cells that ultimately lead to lower IL-17A cytokine levels in lymph nodes, we examined whether ARB inhibits the differentiation of T lymphocytes into Th17 cells.

[0158] As a result, as shown in Fig. 4, both ARBs significantly inhibited the differentiation of naive T cells into Th17 cells at a concentration of 10 μM, and candesartan showed a greater effect than telmisartan (84.5% vs. 29.4%).

[0159]

[0160] 7. Confirmation of inhibition of imiquimod-induced psoriasis by ARB treatment

[0161] Psoriasis is a chronic inflammatory skin disease characterized by a red rash covered with thick, silvery scales, associated with the IL-23 / IL-17 pathway. An imiquimod-induced dermatitis mouse model exhibits erythema, desquamation, and acanthosis, key features of psoriasis. Imiquimod activates toll-like receptor 7, leading to excessive secretion of inflammatory cytokines, including IFN-α, IL-6, and tumor necrosis factor (TNF)-α. These cytokines act on keratinocytes by increasing IL-12 / IL-23 secretion and IL-17 production, ultimately inducing robust proliferation.

[0162] Both telmisartan and candesartan inhibited the differentiation of T lymphocytes into Th17 cells. The effect of ARB was further confirmed in an imiquimod-induced psoriasis mouse model. Referring to Figure 5, the thickness, erythema, and scaling of skin lesions increased along with the total PASI score 3-4 days after starting imiquimod administration, but were reduced by ARB administration. Significant changes in PASI scores were observed on days 5-6 in the candesartan group and on days 6-7 in the telmisartan group, showing that the effect of candesartan was greater than that of telmisartan (42.03% vs. 23.48%).

[0163] Referring to Figure 6(A), epidermal proliferation and leukocyte recruitment into the skin were observed in H&E-stained skin tissue sections in the imiquimod-treated group and were inhibited by ARB. Similarly, Figure 6(C) shows that epidermal thickness was significantly increased by imiquimod but decreased by ARB. Furthermore, referring to Figures 6(B) and 6(D), keratinocyte proliferation, as observed by the number of Ki-67-positive cells, was increased by imiquimod; both telmisartan and candesartan inhibited the increase in Ki-67-positive cells.

[0164] Considering the important role of the IL-23 / IL-17 pathway in the pathogenesis of psoriasis, the mRNA levels of IL-17A, IL-23, and IL-22 were quantified along with those of IFN-γ, TNF-α, and IL-1β. As shown in Figures 7(A) to 7(C), the mRNA levels of IL-17A, IL-23, and IL-22 in skin tissues were increased in the imiquimod-treated group. This suggests the activation of IL-23 / IL-17, which was suppressed by ARB. Similarly, referring to Figures 7(D) to 7(E), the levels of Th1-related cytokines IFN-γ and TNF-α were increased in imiquimod-induced psoriatic skin lesions and suppressed by ARB. The increase in IL-1β levels induced by imiquimod was significantly reduced by candesartan, but not by telmisartan (Figure 7(F)). Therefore, candesartan may act more potently than telmisartan by suppressing cytokine levels of multiple IL-23 / IL-17 pathways, such as IL-23, IFN-γ, and IL-1β.

[0165]

[0166] 8. Confirmation of reduced psoriatic response in lymph nodes and spleen following ARB treatment

[0167] The inguinal lymph nodes are the closest lymphoid organs to the skin, regulating the skin's immune response to imiquimod.

[0168] Referring to Figures 8(A) and 8(D), the isolated lymph nodes and spleen in this experiment were substantially increased in the imiquimod-treated group, and this increase in the size of the lymph nodes and spleen was inhibited by candesartan, but not by telmisartan. The actual enlargement of the lymph nodes and spleen was objectively confirmed by measuring the weight of the lymph nodes and spleen, respectively. As shown in Figures 8(B) and 8(E), the weights of the isolated lymph nodes and spleen were significantly increased by 300% and 90.85%, respectively. Candesartan significantly inhibited the increase in the weight of the lymph nodes and spleen by 57.6% and 63.2%, respectively. This inhibitory effect on the size of the lymph nodes and spleen was not observed with telmisartan.

[0169] Considering that ARB showed significant inhibitory effects on Th17-related cytokines in the skin, CD4 in lymph nodes and spleen + IL17A + As a result of measuring the number of T cells, as shown in Figures 8(C) and 8(F), imiquimod treatment significantly increased CD4 in both lymph nodes and spleen. + IL17A + Candesartan increased the percentage of CD4 T cells in lymph nodes and spleen. + IL17A + The proportion of T cells was significantly suppressed by 43.3% and 78.63%, respectively. The telmisartan administration group significantly suppressed CD4 + IL17A + The proportion of T cells was significantly suppressed by 61.7% in the spleen, but not in the lymph nodes.

[0170]

[0171] 9. Confirmation of inhibition of Th17 and Th1 cytokine increase by imiquimod induction in lymph nodes following ARB treatment

[0172] Inflammatory cytokine levels were assessed by quantifying the mRNA levels of IL-17A, IL-23, and IL-22, along with the levels of IFN-γ, TNF-α, and IL-1β in lymph nodes.

[0173] As a result, referring to Figures 9(A) to 9(C), imiquimod induction substantially increased the levels of cytokines related to the IL-23 / IL-17 pathway (i.e., IL-17A, IL-23, and IL-22) in the lymph nodes. This suggests activation of the IL-23 / IL17 pathway in the lymph nodes of imiquimod-treated mice, and activation of the IL-23 / IL-17 pathway was inhibited by ARB.

[0174] Additionally, as shown in Figures 9(D) to 9(F), the levels of Th1-related cytokines (i.e., IFN-γ, TNF-α, IL-1β) were also increased in the lymph nodes of imiquimod-treated mice, but this was suppressed by ARB. Candesartan induced suppression of IL-23, IFN-γ, IL-22, and IL-1β.

[0175]

[0176] While specific aspects of the present invention have been described in detail above, it should be apparent to those skilled in the art that these specific descriptions merely represent preferred embodiments and are not intended to limit the scope of the present invention. In other words, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A pharmaceutical composition for preventing or treating atopic dermatitis or psoriasis, containing candesartan or a pharmaceutically acceptable salt thereof as an active ingredient.

2. In paragraph 1, The above composition, A pharmaceutical composition characterized by inhibiting differentiation of T cells into helper T cell 17 (Th17) cells.

3. In paragraph 1, The above composition, A pharmaceutical composition characterized by inhibiting the production of Th1, Th2, Th22 or Th17 related cytokines.

4. In paragraph 1, The above composition, A pharmaceutical composition characterized by inhibiting mast cell infiltration.

5. In paragraph 1, The above composition, A pharmaceutical composition characterized by inhibiting the proliferation of Ki-67 positive cells.

6. A cosmetic composition for preventing or improving atopic dermatitis or psoriasis, containing candesartan or a pharmaceutically acceptable salt thereof as an active ingredient.

7. A health functional food composition for preventing or improving atopic dermatitis or psoriasis, containing candesartan or a food-related acceptable salt thereof as an active ingredient.

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