Gel composition for the prevention or treatment of atopic dermatitis

Abstract

The present invention relates to a gel composition containing taurodeoxycholic acid, a derivative thereof, or a pharma- ceutical acceptable salt thereof as an active ingredient, hyaluronic acid, a derivative thereof, or a pharma- ceutical acceptable salt thereof, and a surfactant, polysorbate 20 or polysorbate 80, and a composition for preventing or treating atopic dermatitis, comprising the same. Specifically, the composition has fewer side effects and a high therapeutic effect compared to existing atopic dermatitis treatment agents, and also has a significantly superior effect compared to conventional preparations, and therefore can be usefully used as a new pharmaceutical composition for preventing or treating atopic dermatitis.

Description

Technical Field

[0001] The present invention relates to a gel composition containing taurodeoxycholic acid, a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient, further comprising hyaluronic acid, a derivative thereof or a pharmaceutically acceptable salt thereof, and a surfactant that is polysorbate 20 or polysorbate 80, to the use thereof for preventing, treating or improving atopic dermatitis, and to a method for producing the same.

Background Art

[0002] In 1925, Coca first described the tendency of developing dermatitis, asthma and hyperpyrexia in response to substances exposed via food and the respiratory tract as atopy. In addition to atopic dermatitis, atopic diseases include asthma, allergic rhinitis, and allergic conjunctivitis. The incidence of atopic dermatitis tends to increase rapidly worldwide due to factors such as an increase in environmental pollutants, and the prevalence reaches 20% of the total global population. Patients with atopic dermatitis suffer from reduced quality of life due to restrictions on daily life, and the economic burden of treatment is increasing socially. Therefore, there is an urgent need for atopy treatment and management measures. Atopic dermatitis is a recurrent chronic skin disease accompanied by intense itching that mainly begins in infancy or early childhood, and is a very common skin disease associated with a family history. Symptoms begin in infancy and early childhood, particularly around two months after birth. About 50% of cases occur before 2 years of age, and most patients develop symptoms before 5 years of age, while it is extremely rare for symptoms to appear for the first time in adults. In some patients, symptoms alleviate or resolve spontaneously with growth, and more than half of patients with onset in infancy improve before 2 years of age. The shape and distribution of skin lesions show characteristic findings, and the condition is accompanied by pruritus (itching), dry skin, and characteristic eczema. In infancy, eczema first develops on the face and the extensor sides of the limbs, and as the patient grows, eczema characteristically appears in the flexural areas of the elbows and the popliteal fossa. In adults, lichenification, which is thickening of the skin in flexural areas, occurs, and eczema often develops on areas other than the limbs, such as the face, chest and neck, compared with childhood.

[0003] Atopic dermatitis is generally accompanied by an allergic reaction. In particular, atopic dermatitis is not simply a skin disease, but a signal of the allergic march, similar to allergic asthma and rhinitis. However, the exact cause and mechanism of atopic dermatitis have not yet been elucidated, and there is currently no effective treatment that can completely cure it. Currently, antihistamines, steroids, and immunomodulators are used as treatments for atopic dermatitis. Anti-inflammatory and analgesic drugs and steroid immunosuppressants are mainly used to alleviate inflammation and immune responses. While they have the advantage of showing rapid improvement, symptoms can rapidly worsen if the dosage is reduced or stopped, and long-term use can lead to systemic side effects such as adrenal insufficiency, diabetes, peptic ulcers, hirsutism, alopecia, and discoloration, and can even cause cataracts, especially in children. Steroid ointments can induce serious side effects such as thinning and atrophy of the skin, redness due to increased blood vessels, and folliculitis. Elidel (pimecrolimus) cream and Protopic (tacrolimus, FK506), non-steroidal immunomodulators, were developed as alternatives to steroid ointments. They exhibited no side effects associated with existing steroid ointments during long-term application, were frequently used on sensitive skin such as the face and neck, and rapidly grew to 30% of the overall atopic dermatitis market. However, recent concerns about the potential cancer-inducing properties of calcineurin inhibitors have led to their use being permitted only at low concentrations in patients under 16 years of age, and even at low concentrations in children under 2 years of age, resulting in declining sales. Other atopic dermatitis treatments include antihistamines and, in severe cases, short-term administration of corticosteroids and topical application. Skin ultraviolet therapy and interferon treatment are also employed, but while most show temporary improvement, the disease recurs once medication is stopped, making it a difficult-to-treat condition. Therefore, there is a pressing need for the development of therapeutic and preventive drugs that exhibit higher efficacy and fewer side effects than existing treatments.

[0004] As a result, the inventors have confirmed that a gel composition containing taurodeoxycholic acid, its derivatives or pharmaceutically acceptable salts thereof as an active ingredient, and containing hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof, and a surfactant such as polysorbate 20 or polysorbate 80, is considerably effective in treating atopic dermatitis and shows significantly superior effects compared to existing dosage forms. The inventors have completed the present invention by clarifying that the composition can be used for the prevention, treatment, and improvement of atopic dermatitis. [Overview of the project] [Problems that the invention aims to solve]

[0005] The object of the present invention is to provide a gel composition containing taurodeoxycholic acid, its derivatives or pharmaceutically acceptable salts thereof as an active ingredient, hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof, and a surfactant which is polysorbate 20 or polysorbate 80, and an agent for the prevention or treatment of atopic dermatitis containing the same.

[0006] Another object of the present invention is to provide a method for preventing, improving, or treating atopic dermatitis, which includes the step of administering the gel composition to an individual.

[0007] Another object of the present invention is to provide the use of the gel composition for use as a pharmaceutical composition for the prevention or treatment of atopic dermatitis.

[0008] Furthermore, another object of the present invention is to provide the use of the gel composition for use as a cosmetic composition for the prevention or improvement of atopic dermatitis. [Means for solving the problem]

[0009] To achieve the above objective, the present invention provides a gel composition containing taurodeoxycholic acid, its derivatives or pharmaceutically acceptable salts thereof; hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof; and a surfactant which is polysorbate 20 or polysorbate 80 as an active ingredient.

[0010] Furthermore, the gel composition can be used as a composition for the prevention or treatment of atopic dermatitis.

[0011] Furthermore, the gel composition can be used as a cosmetic composition for preventing or improving atopic dermatitis.

[0012] Furthermore, the present invention provides a method for preventing or improving atopic dermatitis, which includes the step of administering the gel composition to an individual.

[0013] Furthermore, the present invention provides a method for treating atopic dermatitis, which includes the step of administering the gel composition to an individual.

[0014] Furthermore, the present invention provides the use of the gel composition for use as a pharmaceutical composition for the prevention or treatment of atopic dermatitis.

[0015] Furthermore, the present invention provides the use of the gel composition for use as a cosmetic composition for preventing or improving atopic dermatitis. [Effects of the Invention]

[0016] The gel composition according to the present invention has been confirmed to have fewer side effects and higher therapeutic efficacy compared to existing atopic dermatitis treatments, and to exhibit remarkable effects compared to conventional dosage forms, making it useful as a composition for the prevention, treatment, or improvement of atopic dermatitis. [Brief explanation of the drawing]

[0017] [Figure 1]Figure 1 shows the administration times for DNCB to induce atopic dermatitis in mice, and the administration times for 0.5% HY209_HA gel and 5% HY209_PEG gel to treat atopic dermatitis. [Figure 2] Figure 2 shows the sites of atopic dermatitis induction in mice treated with various therapeutic agents, including 0.5% HY209_HA gel and 5% HY209_PEG gel, after atopic dermatitis induction with DNCB. [Figure 3] Figure 3 is a graph showing the results of sensory evaluation of mice treated with various therapeutic agents, including 0.5% HY209_HA gel and 5% HY209_PEG gel, after atopic dermatitis induction using DNCB. [Figure 4] Figure 4 is a graph showing the diverse cytokine suppression capabilities of mice treated with various therapeutic agents, including 0.5% HY209_HA gel and 5% HY209_PEG gel, after atopic dermatitis induction with DNCB. [Figure 5] Figure 5 shows a comparison of the epithelium and dermis of mice treated with various therapeutic agents, including 0.5% HY209_HA gel and 5% HY209_PEG gel, after atopic dermatitis induction using DNCB. [Figure 6] Figure 6 is a graph showing the results of epithelial thickness measurements in mice treated with various therapeutic agents, including 0.5% HY209_HA gel and 5% HY209_PEG gel, after atopic dermatitis induction using DNCB. [Figure 7] Figure 7 is a graph showing the dermal thickness measurements of mice treated with various therapeutic agents, including 0.5% HY209_HA gel and 5% HY209_PEG gel, after atopic dermatitis induction using DNCB. [Figure 8] Figure 8 is a graph showing the results of spleen weight measurements in mice treated with various therapeutic agents, including 0.5% HY209_HA gel and 5% HY209_PEG gel, after atopic dermatitis induction using DNCB. [Figure 9] Figure 9 shows the administration time of MC903 for inducing atopic dermatitis in mice and the administration time of 0.5% HY209_HA gel for treating atopic dermatitis. [Figure 10]Figure 10 is a diagram showing atopic dermatitis induction sites in mice treated with various therapeutic agents including 0.5% HY209_HA gel after induction of atopic dermatitis with MC903, and graphs showing sensory evaluation results and ear thickness. [Figure 11] Figure 11 is a diagram comparatively showing the epithelium and dermis of mice treated with various therapeutic agents including 0.5% HY209_HA gel after induction of atopic dermatitis with MC903, and a graph showing measurement results of epithelial and dermal thickness. [Figure 12] Figure 12 is a diagram showing the oxazolone administration time for inducing atopic dermatitis in mice and the administration time of 0.5% HY209_HA gel for treating atopic dermatitis. [Figure 13] Figure 13 is a diagram showing atopic dermatitis induction sites in mice treated with various therapeutic agents including 0.5% HY209_HA gel after induction of atopic dermatitis with oxazolone, and graphs showing sensory evaluation results and ear thickness. [Figure 14] Figure 14 is a diagram comparatively showing the epithelium and dermis of mice treated with various therapeutic agents including 0.5% HY209_HA gel after induction of atopic dermatitis with oxazolone, and a graph showing measurement results of epithelial and dermal thickness. Best Mode for Carrying Out the Invention

[0018] Hereinafter, the present invention will be described in more detail.

[0019] The present invention provides a gel composition containing, as active ingredients: taurodeoxycholic acid, a derivative thereof or a pharmaceutically acceptable salt thereof; hyaluronic acid, a derivative thereof or a pharmaceutically acceptable salt thereof; and a surfactant which is polysorbate 20 or polysorbate 80.

[0020] The present invention also relates to taurodeoxycholic acid, a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient for use as a pharmaceutical composition for preventing or treating atopic dermatitis; Hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof; and This invention provides applications for gel compositions containing a surfactant that is polysorbate 20 or polysorbate 80.

[0021] In the present invention, the taurodeoxycholic acid may be sodium taurodeoxycholic acid, but is not limited thereto.

[0022] In the present invention, taurodeoxycholic acid, its derivatives, or pharmaceutically acceptable salts may be included as an active ingredient in amounts of 0.01 to 3 w / v%; specifically 0.01 to 1 w / v%; more specifically 0.02 to 0.5 w / v%; or more specifically 0.05 to 0.1 w / v% of the total gel composition.

[0023] In the present invention, the hyaluronic acid, its derivatives, or pharmaceutically acceptable salts thereof may be sodium hyaluronic acid.

[0024] In the present invention, the hyaluronic acid, its derivatives, or pharmaceutically acceptable salts thereof may be present in amounts of 0.1 to 2 w / v%; specifically 0.1 to 2 w / v%; 0.5 to 1.5 w / v%; or more specifically 1 w / v% relative to the overall gel composition.

[0025] In the present invention, the surfactant, which is polysorbate 20 or polysorbate 80, may be included in the overall gel composition in an amount of 0.01 to 1 w / v%; specifically 0.02 to 0.5 w / v%; more specifically 0.03 to 0.1 w / v%; more specifically 0.05 w / v%.

[0026] In this invention, polysorbate 20 can be used as a surfactant.

[0027] In the present invention, the gel composition may additionally contain a preservative.

[0028] In the present invention, methyl parahydroxybenzoate can be used as the preservative.

[0029] In the present invention, the preservative may be included in the total gel composition at an amount of 0.05 to 1 w / v%; more specifically 0.1 to 0.5 w / v%; more specifically 0.2 w / v%.

[0030] In the present invention, the gel composition may, but is not limited to, contain additives such as stabilizers, wetting agents and / or emulsifiers, solubilizers, solvents, salts and / or buffers for adjusting osmotic pressure.

[0031] In the present invention, the gel composition may be a pharmaceutical composition for the prevention or treatment of atopic dermatitis.

[0032] In the present invention, the gel composition may be a cosmetic composition for the prevention or improvement of atopic dermatitis.

[0033] In the present invention, the gel composition may be a gel composition for animals used to prevent, improve, or treat atopic dermatitis.

[0034] In the present invention, the dosage of the gel composition containing taurodeoxycholic acid, its derivatives, or pharmaceutically acceptable salts as active ingredients can vary depending on various factors, such as the efficacy and duration of action of the active ingredient, the method of administration, the sex, age, weight, and other individual conditions of the warm-blooded animal, as well as the severity of the disease. The specific route of administration and dosage can be selected by the attending physician / veterinarian based on the characteristics of the individual receiving the administration, i.e., age, weight, disease state, physical condition, etc.

[0035] In this invention, (a) A step of obtaining a gel-type product by combining taurodeoxycholic acid, its derivatives or pharmaceutically acceptable salts thereof; and hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof; and (b) A method for producing a gel composition is provided, comprising the step of adding a surfactant which is polysorbate 20 or polysorbate 80 and stirring.

[0036] In step (a) above, the taurodeoxycholic acid may be sodium taurodeoxycholic acid, and taurodeoxycholic acid, its derivatives, or pharmaceutically acceptable salts may be present in the overall gel composition in amounts of 0.01 to 3 w / v%; specifically 0.01 to 1 w / v%; more specifically 0.02 to 0.5 w / v%; more specifically 0.05 to 0.1 w / v%.

[0037] In step (a) above, the hyaluronic acid, its derivatives, or pharmaceutically acceptable salts thereof may be sodium hyaluronic acid, and the hyaluronic acid, its derivatives, or pharmaceutically acceptable salts thereof may be included in the overall gel composition in amounts of 0.1 to 2 w / v%; specifically 0.1 to 2 w / v%; 0.5 to 1.5 w / v%; more specifically 1 w / v%.

[0038] In step (b) above, the surfactant, which is polysorbate 20 or polysorbate 80, may be included in the overall gel composition in an amount of 0.01 to 1 w / v%; more specifically 0.02 to 0.5 w / v%; more specifically 0.03 to 0.1 w / v%; more specifically 0.05 w / v%.

[0039] In a specific embodiment of the present invention, the inventors prepared a HY209 gel containing sodium taurodeoxycholic acid and added sodium hyaluronate. The HY209 gel was then applied to mice in which atopic dermatitis had been induced. The results showed that the 0.5% HY209 gel exhibited significant effects on various symptoms of atopic dermatitis, and was particularly superior to existing atopic dermatitis treatments and the inventors' own products.

[0040] Therefore, the composition for the prevention, treatment, or improvement of atopic dermatitis, which contains taurodeoxycholic acid and its derivatives as active ingredients and hyaluronic acid and its derivatives as excipients, shows a significant therapeutic or ameliorative effect on atopic dermatitis in skin application experiments on mice in which atopic dermatitis has been induced. Thus, the composition can be usefully used as an active ingredient in compositions for the prevention, treatment, or improvement of atopic dermatitis.

[0041] Furthermore, this invention The active ingredient is taurodeoxycholic acid, its derivatives, or pharmaceutically acceptable salts thereof; Hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof; and Contains a surfactant of polysorbate 20 or polysorbate 80. The present invention provides a method for preventing or improving atopic dermatitis, which includes the step of administering a gel composition to an individual.

[0042] Furthermore, the present invention The active ingredient is taurodeoxycholic acid, its derivatives, or pharmaceutically acceptable salts thereof; Hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof; and Contains a surfactant of polysorbate 20 or polysorbate 80. The present invention provides a method for treating atopic dermatitis, which includes the step of administering a gel composition to an individual.

[0043] The aforementioned taurodeoxycholic acid, its derivatives or pharmaceutically acceptable salts thereof, hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof, surfactants such as polysorbate 20 or polysorbate 80, and atopic dermatitis are the same as described for the gel composition, and specific descriptions are referenced from the above.

[0044] On the other hand, the gel composition produced by the method of the present invention has fewer side effects and higher therapeutic efficacy compared to existing atopic dermatitis treatments, and has been shown to be significantly superior to conventional dosage forms. Therefore, the gel composition of the present invention can be usefully used for the prevention, improvement, or treatment of atopic dermatitis.

[0045] The present invention will be described in detail below with reference to examples, comparative examples, and experimental examples.

[0046] However, the following examples, comparative examples, and experimental examples are illustrative of the present invention, and the content of the present invention is not limited to the following examples, comparative examples, and experimental examples.

[0047] <Example 1> Sample Preparation

[0048] A 0.5% HY209 gel containing sodium tauro deoxycholate (TDCA) was prepared as a composition for the prevention or treatment of atopic dermatitis, according to the composition shown in Table 1 below.

[0049] Sodium taurodeoxycholic acid powder was mixed and dissolved in 20 ml of purified water and polysorbate 80. Then, methyl parahydroxybenzoate and 70 ml of distilled water were mixed with the 25% sodium taurodeoxycholic acid solution. Sodium hyaluronate was added to the mixed solution, and then purified water was added to make a total volume of 1000 ml.

[0050] JPEG0007919726000001.jpg55152

[0051] <Comparative Example 1> Manufacturing of 5%HY209_PEGgel (gel) with different excipients

[0052] The sodium taurodeoxycholic acid powder from Example 1 was dissolved in a solution of polyethylene glycol 400 solution (10% in distilled water) and ethanol stock solution mixed in a 7:3 ratio to a concentration of 5%, and then filtered through a 0.4 μm filter to produce the product.

[0053] <Example 2> Production of an animal model of atopic dermatitis induced by DNCB

[0054] 2,4-Dinitrochlorobenzene(2,4-dinitrochloro A 200 ml solution of 1% or 2% DNCB dissolved in acetone was applied twice daily for two days to the backs of depilated mice. On the third day, another 200 ml solution of DNCB dissolved in acetone at a concentration of 1% was applied twice daily. On the 10th or 11th day from the start of DNCB solution application, an additional 200 ml solution of DNCB dissolved in acetone at a concentration of 1% or a 10-fold diluted solution of the above solution was applied twice daily to the backs of the depilated mice to induce atopic dermatitis (Figure 1).

[0055] <Experimental Example 1> Comparative confirmation of the therapeutic effects of 0.5% HY209_HAgel and our existing product 5% HY209_PEGgel on atopic dermatitis in an animal model using visual observation and sensory evaluation.

[0056] To compare and confirm the therapeutic effects of 0.5% HY209_HA gel and 5% HY209_PEG gel on atopic dermatitis through visual observation and sensory evaluation in the atopic dermatitis-inducing animal model described in Example 2, five mice each were randomly assigned to one of the following treatment groups based on their treatment method: DNCB group, 0.5% HY209_HA gel group, 5% HY209_PEG gel group, Dexamethasone (DEX) (Maxidex ointment, Alcon Pharmaceuticals) group, Crisabolole (Ukrisa ointment, Pfizer Pharmaceuticals) group, Tofacitinib group, and FK506 (Tacrolimus) (Protopic ointment, Leoparm).

[0057] Visual observation and sensory evaluation were performed on the back area where atopic dermatitis was induced in each group of mice to check for improvement in atopic dermatitis. Sensory evaluation was performed on the 15th day after the start of DNCB solution application, assigning points from 0 to 3 for each of the following: the number of times scratching for 2 minutes, erythema and bleeding, edema, abrasions and sores, scaling and dryness, and so on. The total score was calculated out of 15 points. After three people performed blinded evaluations, the average score for each individual mouse was calculated.

[0058] As a result, it was confirmed that the 0.5% HY209_HA gel group and the 5% HY209_PEG gel group showed a significant decrease in the sensory evaluation index for atopic dermatitis compared to the DNCB group. In particular, in the case of the 0.5% HY209_HA gel group, it was confirmed that the symptoms of atopic dermatitis improved significantly compared to the DEX group, Crisaborole group, Tofacitinib group, and FK506 group used as positive control groups. When compared to our existing product, the 5% HY209_PEG gel group, it was confirmed that the therapeutic effect was equivalent to or better than that of the HY209 gel group, even though the dose of HY209 was reduced by 10 times (Figures 2 and 3).

[0059] <Experimental Example 2> Comparative confirmation of the therapeutic effects of 0.5% HY209_HAgel and our existing product 5% HY209_PEGgel on atopic dermatitis in an animal model using serum analysis.

[0060] To compare and confirm the therapeutic effects of 0.5% HY209_HA gel and 5% HY209_PEG gel on atopic dermatitis in the atopic dermatitis-inducing animal model described in <Example 2>, individuals in each group who had completed the evaluation in <Experimental Example 1> were injected with an anesthetic prepared by mixing 250 mg / 5 cc of zoletil and 2% rompun solution in an 8:2 (v / v) ratio, diluting this mixture 10-fold with saline, and then blood was collected from the heart. Serum analysis was then performed using the usual method.

[0061] As a result, serum cytokine concentrations in the 0.5% HY209_HA gel group and the 5% HY209_PEG gel group were found to improve atopic dermatitis compared to serum cytokine concentrations in the DEX group and the FK506 group (Figure 4).

[0062] <Experimental Example 3> Comparative confirmation of the therapeutic effects of 0.5% HY209_HAgel and our existing product 5% HY209_PEGgel on atopic dermatitis in an animal model using epithelial and dermal thickness measurement.

[0063] To compare and confirm the therapeutic effects of 0.5% HY209_HA gel and 5% HY209_PEG gel on atopic dermatitis through epithelial and dermal thickness measurements in the atopic dermatitis-inducing animal model described in <Example 2>, the areas of atopic dermatitis were scarity-cut 15 days after the induction of atopic dermatitis in each individual in the groups treated with 0.5% HY209_HA gel, 5% HY209_PEG gel, Maxidex ointment, Ucrisa ointment, and Protopic ointment in <Experimental Example 1>. The sham (untreated) group, in which atopic dermatitis was not induced, and the DNCB group, in which atopic dermatitis was induced but not treated, were also scarity-cut 15 days later.

[0064] After collecting skin tissue from mice in each group, the collected tissue samples were cut and fixed in 10% formalin solution for 24 hours. They were then washed with distilled water, and the fixed skin tissue was made into paraffin blocks. These blocks were then cut into 7 μm thick sections, stained with hematoxylin and eosin (H&E), observed using a light microscope, and then the epithelial and dermal thicknesses were measured using image analysis software and analyzed using analytical software.

[0065] As a result, the DNCB group showed an increase in epithelial and dermal thickness compared to the Sham group. In contrast, the 0.5% HY209_HA gel group, 5% HY209_PEG gel group, DEX group, Crisaborole group, and FK506 group showed a significant decrease in epithelial thickness compared to the DNCB group, while the dermal thickness recovered to a level close to that of the normal Sham group. Furthermore, when comparing the 0.5% HY209_HA gel group with our existing 5% HY209_PEG gel group, it was confirmed that it had an equivalent or greater restorative effect despite a tenfold reduction in the volume of HY209 (Figures 5 to 7).

[0066] <Experimental Example 4> Comparative confirmation of the therapeutic effects of 0.5% HY209_HAgel and our existing product 5% HY209_PEGgel on atopic dermatitis using an animal model by measuring the weight of the spleen.

[0067] To compare and confirm the therapeutic effects of 0.5% HY209_HA gel and 5% HY209_PEG gel on atopic dermatitis through spleen weight measurement in the atopic dermatitis-inducing animal model of <Example 2>, individuals from each group treated with 0.5% HY209_HA gel, 5% HY209_PEG gel, Maxidex ointment, Ucrisa ointment, topacitinib, and Protopic ointment in <Experimental Example 1> were sacrificed on day 15 from the day atopic dermatitis was induced. The Sham (untreated) group, in which atopic dermatitis was not induced, and the DNCB group, in which atopic dermatitis was induced but not treated, were also sacrificed on day 15.

[0068] After collecting spleen tissue from the sacrificial mice in each group, the weight of the collected spleen samples was measured.

[0069] As a result, it was confirmed that the weight of the spleen enlarged by DNCB was similar in the group treated with 0.5% HY209_HA gel to that of the Sham group, and that the general health and immune status of the mice recovered to near-normal levels. Furthermore, when compared to the group treated with our existing 5% HY209_PEG gel, it was confirmed that the therapeutic effect was equivalent to or better than that of the Sham group, even though the volume of HY209 was reduced by 10 times (Figure 8).

[0070] <Example 3> Production of an atopic dermatitis-inducing animal model using MC903

[0071] A 1 nM solution of calcipotriol (MC903) was applied twice daily to the backs of hairless mice for 9 days to induce atopic dermatitis (Figure 9).

[0072] <Experimental Example 5> Confirmation of the therapeutic effect of 0.5% HY209_HAgel on atopic dermatitis in an animal model using visual observation and sensory evaluation.

[0073] To confirm the therapeutic effect of 0.5% HY209_HA gel on atopic dermatitis through visual observation and sensory evaluation in the atopic dermatitis-inducing animal model described in Example 3, five mice each were randomly assigned to the MC903 group and the 0.5% HY209_HA gel group according to the treatment method, based on the atopic dermatitis-inducing mice prepared in Example 3.

[0074] Visual observation and sensory evaluation were performed on the back area where atopic dermatitis was induced in each group of mice to check for improvement in atopic dermatitis. Sensory evaluation was performed on the 10th day after the start of MC903 solution application, assigning points from 0 to 3 for each of the following: the number of times scratching was performed for 2 minutes, erythema and bleeding, edema, abrasions and sores, scaling and dryness, etc., with a total score of 15 points. After three people performed blinded evaluations, the average score for each individual mouse was calculated.

[0075] As a result, the 0.5% HY209_HA gel group showed a significant decrease in the sensory evaluation index for atopic dermatitis compared to the MC903 group, and measurement of ear thickness also confirmed that it had a therapeutic effect on the symptoms of atopic dermatitis (Figure 10).

[0076] <Experimental Example 6> Confirmation of the therapeutic effect of 0.5% HY209_HAgel on atopic dermatitis in an animal model using epithelial and dermal thickness measurement.

[0077] To confirm the therapeutic effect of 0.5% HY209_HA gel on atopic dermatitis through epithelial and dermal thickness measurement in the atopic dermatitis-inducing animal model of <Example 3> described above, each individual in the group to which 0.5% HY209_HA gel was applied in <Experimental Example 5> described above had the atopic dermatitis site scarified 10 days after the induction of atopic dermatitis. The Sham (untreated) group, which had not had atopic dermatitis induced, and the MC903 group, which had atopic dermatitis induced but had not been treated, also had their tissues scarityed on 10 days.

[0078] After collecting skin tissue from mice in each group, the collected tissue samples were cut and fixed in 10% formalin solution for 24 hours. They were then washed with distilled water, and the fixed skin tissue was made into paraffin blocks. These blocks were then cut into 7 μm thick sections, stained with hematoxylin and eosin (H&E), observed using a light microscope, and then the epithelial and dermal thicknesses were measured using image analysis software and analyzed using analytical software.

[0079] As a result, the MC903 group showed an increase in epithelial and dermal thickness compared to the Sham group. In contrast, the 0.5% HY209_HA gel group showed a significant decrease in skin epithelial thickness compared to the MC903 group, and its dermal thickness recovered to a level close to that of the normal Sham group (Figure 11).

[0080] <Example 4> Production of an animal model of atopic dermatitis induced by oxazolone

[0081] A 1% oxazolone solution was applied once to the backs of depilated mice, and then 0.1% oxazolone was applied twice daily on days 8, 10, and 15 to induce atopic dermatitis (Figure 12).

[0082] <Experimental Example 7> Confirmation of the therapeutic effect of 0.5% HY209_HAgel on atopic dermatitis in an animal model using visual observation and sensory evaluation.

[0083] To confirm the therapeutic effect of 0.5% HY209_HA gel on atopic dermatitis through visual observation and sensory evaluation in the atopic dermatitis-inducing animal model described in Example 4, five mice each were randomly assigned to the oxazolone group and the 0.5% HY209_HA gel group according to the treatment method, based on the atopic dermatitis-inducing mice prepared in Example 4.

[0084] Visual observation and sensory evaluation were performed on the back area where atopic dermatitis was induced in each group of mice to check for improvement in atopic dermatitis. Sensory evaluation was performed on the 17th day after the start of oxazolone solution application, assigning points from 0 to 3 for each condition according to the number of times scratching was performed for 2 minutes, erythema and bleeding, edema, abrasions and sores, scaling and dryness, for a total of 15 points. After three people performed blinded evaluations, the average score for each individual mouse was calculated.

[0085] As a result, the 0.5% HY209_HA gel group showed a significant decrease in the sensory evaluation index for atopic dermatitis compared to the oxazolone group, and measurement of ear thickness also confirmed that it had a therapeutic effect on the symptoms of atopic dermatitis (Figure 13).

[0086] <Experimental Example 8> Confirmation of the therapeutic effect of 0.5% HY209_HAgel on atopic dermatitis in an animal model using epithelial and dermal thickness measurement.

[0087] To confirm the therapeutic effect of 0.5% HY209_HA gel on atopic dermatitis through epithelial and dermal thickness measurements in the atopic dermatitis-inducing animal model described in <Example 4>, the atopic dermatitis-affected areas of each individual in the group treated with 0.5% HY209_HA gel in <Experimental Example 7> were scarityed on the 17th day after the induction of atopic dermatitis. The sham (untreated) group, in which atopic dermatitis was not induced, and the oxazolone group, in which atopic dermatitis was induced but not treated, were also scarityed on the 17th day.

[0088] After collecting skin tissue from mice in each group, the collected tissue samples were cut and fixed in 10% formalin solution for 24 hours. They were then washed with distilled water, and the fixed skin tissue was made into paraffin blocks. These blocks were then cut into 7 μm thick sections, stained with hematoxylin and eosin (H&E), observed using a light microscope, and then the epithelial and dermal thicknesses were measured using image analysis software and analyzed using analytical software.

[0089] As a result, the oxazolone group showed an increase in epithelial and dermal thickness compared to the Sham group. In contrast, the 0.5% HY209_HA gel group showed a significant decrease in skin epithelial thickness compared to the oxazolone group, and the dermal thickness recovered to a level close to that of the normal Sham group (Figure 14). [Industrial applicability]

[0090] The present invention relates to a gel composition containing taurodeoxycholic acid, its derivatives or pharmaceutically acceptable salts thereof as an active ingredient, hyaluronic acid, its derivatives or pharmaceutically acceptable salts thereof, and polysorbate 20 or polysorbate 80 surfactant, and a composition for the prevention or treatment of atopic dermatitis containing the same. Specifically, the aforementioned composition has the advantages of having fewer side effects and higher therapeutic efficacy compared to existing atopic dermatitis treatments, and having significantly superior efficacy compared to conventional formulations, and can be usefully utilized.

Claims

1. The active ingredient is taurodeoxycholic acid or a pharmaceutically acceptable salt thereof; Hyaluronic acid or its pharmaceutically acceptable salts; and A gel composition containing polysorbate 80.

2. The gel composition according to claim 1, characterized in that the taurodeoxycholic acid or a pharmaceutically acceptable salt thereof is sodium taurodeoxycholic acid.

3. As an active ingredient, taurodeoxycholic acid or a pharmaceutically acceptable salt thereof is The gel composition according to claim 1, characterized in that it is contained in an amount of 0.01 to 3 w / v% relative to the entire gel composition.

4. As an active ingredient, taurodeoxycholic acid or a pharmaceutically acceptable salt thereof is The gel composition according to claim 1, characterized in that it is contained in an amount of 0.02 to 0.5 w / v% relative to the overall gel composition.

5. As an active ingredient, taurodeoxycholic acid or a pharmaceutically acceptable salt thereof is The gel composition according to claim 1, characterized in that it is contained in an amount of 0.05 to 0.1 w / v% relative to the entire gel composition.

6. The gel composition according to claim 1, characterized in that the hyaluronic acid or a pharmaceutically acceptable salt thereof is sodium hyaluronic acid.

7. Hyaluronic acid or a pharmaceutically acceptable salt thereof is The gel composition according to claim 1, characterized in that it is contained in an amount of 0.1 to 2 w / v% relative to the entire gel composition.

8. Hyaluronic acid or a pharmaceutically acceptable salt thereof The gel composition according to claim 1, characterized in that it is contained in an amount of 0.5 to 1.5 w / v% relative to the overall gel composition.

9. Hyaluronic acid or a pharmaceutically acceptable salt thereof The gel composition according to claim 1, characterized in that it is contained in an amount of 1 w / v% relative to the entire gel composition.

10. Polysorbate 80 is The gel composition according to claim 1, characterized in that it is contained in an amount of 0.01 to 1 w / v% relative to the entire gel composition.

11. Polysorbate 80 is The gel composition according to claim 1, characterized in that it is contained in an amount of 0.02 to 0.5 w / v% relative to the overall gel composition.

12. Polysorbate 80 is The gel composition according to claim 1, characterized in that it is contained in an amount of 0.03 to 0.1 w / v% relative to the entire gel composition.

13. Polysorbate 80 is The gel composition according to claim 1, characterized in that it is contained in an amount of 0.05 w / v% relative to the entire gel composition.

14. The gel composition according to claim 1, further comprising a preservative.

15. The gel composition according to claim 14, wherein the preservative is methyl parahydroxybenzoate.

16. The gel composition according to claim 14, characterized in that the preservative is contained in an amount of 0.05 to 1 w / v% relative to the overall gel composition.

17. The gel composition according to claim 14, characterized in that the preservative is contained in an amount of 0.1 to 0.5 w / v% relative to the overall gel composition.

18. The gel composition according to claim 14, characterized in that the preservative is contained in an amount of 0.2 w / v% relative to the total gel composition.

19. A gel composition comprising any one of claims 1 to 18, Pharmaceutical compositions for the prevention or treatment of atopic dermatitis.

20. A gel composition comprising any one of claims 1 to 18, A cosmetic composition for the prevention or improvement of atopic dermatitis.

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