Compositions comprising novel compound

Abstract

The present invention relates to a composition comprising a novel compound, and provides a composition comprising, as an active ingredient, a compound represented by chemical formula 1 or a salt thereof.

Description

Composition comprising a novel compound

[0001] Cross-reference to related applications

[0002] This application claims the benefit of priority to Korean Patent Application No. 2024-0026601, filed February 23, 2024, the contents of which are incorporated herein by reference in their entirety.

[0003] The present invention relates to a composition comprising a novel compound having anti-atopic, antibacterial, cell-promoting and antioxidant activities.

[0004] Atopic syndrome is a condition in which the body induces an allergic reaction without direct contact with an antigen, forming skin irritation and continuously generating skin stress factors, which destroys the skin's homeostasis and causes itching and inflammation.

[0005] It is known that the symptoms of skin inflammation, commonly called atopic dermatitis, are largely caused by environmental and genetic factors, but the exact cause has not yet been identified, so there is no known treatment or definitive method for the treatment.

[0006] Accordingly, the inventors of the present invention have conducted extensive research efforts to discover a novel compound that is safe and exhibits improved anti-atopic activity. As a result, they have confirmed that the compound represented by Chemical Formula 1 not only has excellent anti-atopic activity, but also exhibits antibacterial, cell-promoting, and antioxidant activities, thereby completing the present invention.

[0007] The problem to be solved by the present invention is to provide a composition comprising a novel compound.

[0008] The problem to be solved by the present invention is to provide a cosmetic composition comprising a novel compound.

[0009] The problem to be solved by the present invention is to provide a pharmaceutical composition comprising a novel compound.

[0010] One aspect of the present invention is a composition comprising a compound represented by the following chemical formula 1 or a salt thereof as an active ingredient.

[0011] [Chemical Formula 1]

[0012]

[0013] In the present invention, the composition may have anti-atopic activity.

[0014] In the present invention, the composition may have antibacterial activity.

[0015] In the present invention, the composition may have cell promoting activity.

[0016] In the present invention, the composition may have antioxidant activity.

[0017] Another aspect of the present invention is a cosmetic composition comprising a compound represented by the following chemical formula 1 or a cosmetically acceptable salt thereof as an active ingredient.

[0018] [Chemical Formula 1]

[0019]

[0020] In the present invention, the cosmetic composition may have anti-atopic activity.

[0021] In the present invention, the cosmetic composition may have antibacterial activity.

[0022] In the present invention, the cosmetic composition may have cell promoting activity.

[0023] In the present invention, the cosmetic composition may have antioxidant activity.

[0024] Another aspect of the present invention is a pharmaceutical composition comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0025] [Chemical Formula 1]

[0026]

[0027] In the present invention, the above-mentioned pharmaceutical composition may have anti-atopic activity.

[0028] In the present invention, the above-mentioned pharmaceutical composition may have antibacterial activity.

[0029] In the present invention, the above-mentioned pharmaceutical composition may have cell promoting activity.

[0030] In the present invention, the above-mentioned pharmaceutical composition may have antioxidant activity.

[0031] The present invention relates to the use of a novel compound for the preparation of a composition having anti-atopic activity, antibacterial activity, cell-promoting activity, and antioxidant activity.

[0032] The present invention relates to the use of a novel compound or a cosmetically acceptable salt thereof for the manufacture of a cosmetic composition having anti-atopic activity, antibacterial activity, cell-promoting activity, and antioxidant activity.

[0033] The present invention relates to the use of a novel compound or a pharmaceutically acceptable salt thereof for the manufacture of a pharmaceutical composition having anti-atopic activity, antibacterial activity, cell-promoting activity, and antioxidant activity.

[0034] A composition comprising a novel compound according to the present invention can exhibit excellent anti-atopic, cell proliferation, antioxidant and antibacterial activities.

[0035] Figure 1 is a drawing showing the antibacterial activity of a novel compound (ATO-004).

[0036] Figure 2 is a graph evaluating the cell proliferation activity of a novel compound (ATO-004) in HaCaT cells.

[0037] Figure 3 is a graph evaluating the cell proliferation activity of a novel compound (ATO-004) in HS68 cells.

[0038] Figure 4 is a graph evaluating the antioxidant activity of a novel compound (ATO-004).

[0039] Figure 5 is a graph evaluating the anti-atopic activity of a novel compound (ATO-004).

[0040] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings so that those skilled in the art can easily implement the present invention. However, the present invention may be implemented in various different forms and is not limited to the embodiments described herein.

[0041]

[0042] One aspect of the present invention is a composition comprising a compound represented by the following chemical formula 1 or a salt thereof as an active ingredient.

[0043] [Chemical Formula 1]

[0044]

[0045] In the present invention, the compound represented by the chemical formula 1 has a molecular weight of 334.33.

[0046] In the composition according to the present invention, it is preferable that the compound represented by the chemical formula 1 is present in an amount of 0.0001 to 20 wt% relative to the total weight of the composition.

[0047] In the present invention, the composition may have anti-atopic, antibacterial, cell-promoting or antioxidant activity.

[0048] In the present invention, antibacterial activity was confirmed through dandruff fungi, cell promoting activity was confirmed through HaCaT cells and HS68 cells, antioxidant activity was confirmed through DCFDA experiment, and anti-atopic activity was confirmed through regulation of IL-5 expression.

[0049]

[0050] Another aspect of the present invention is a cosmetic composition comprising a compound represented by the following chemical formula 1 or a cosmetically acceptable salt thereof as an active ingredient.

[0051] [Chemical Formula 1]

[0052]

[0053] In the cosmetic composition according to the present invention, it is preferable that the compound represented by the chemical formula 1 is present in an amount of 0.0001 to 20 wt% relative to the total weight of the cosmetic composition.

[0054] In the present invention, the cosmetic composition may have anti-atopic, antibacterial, cell-promoting or antioxidant activities.

[0055] The cosmetic composition of the present invention may contain, without limitation, conventionally acceptable ingredients in addition to the compound represented by the above chemical formula 1, and may include conventional auxiliary agents such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and fragrances, and carriers.

[0056] The cosmetic composition according to the present invention can be prepared in one or more formulations selected from the group consisting of solutions, external ointments, creams, foams, nourishing toners, emollients, packs, emollients, emulsions, makeup bases, essences, soaps, liquid cleansers, bath products, sunscreen creams, sun oils, suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, patches, and sprays, but is not limited thereto.

[0057] In addition, the cosmetic composition of the present invention may additionally include one or more cosmetically acceptable carriers that are incorporated into general skin cosmetics, and may appropriately incorporate conventional ingredients such as oil, water, surfactants, moisturizers, lower alcohols, thickeners, chelating agents, pigments, preservatives, fragrances, etc., but is not limited thereto. The cosmetically acceptable carriers included in the cosmetic composition of the present invention vary depending on the formulation.

[0058] When the formulation of the present invention is an ointment, paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or a mixture thereof may be used as a carrier component.

[0059] When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or a mixture thereof may be used as a carrier component, and particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether may be additionally included.

[0060] When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, and for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil can be used, and in particular, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol fatty acid ester, polyethylene glycol or fatty acid ester of sorbitan can be used.

[0061] When the formulation of the present invention is a suspension, 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, etc. can be used as a carrier component.

[0062] When the formulation of the present invention is soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolysates, isethionates, lanolin derivatives, fatty alcohols, vegetable oils, glycerol, sugars, etc. can be used as carrier components.

[0063] When the formulation of the present invention is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcositate, fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester may be used as a carrier component.

[0064]

[0065] Another aspect of the present invention is a pharmaceutical composition comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0066] [Chemical Formula 1]

[0067]

[0068] In the quasi-drug composition according to the present invention, it is preferable that the compound represented by the chemical formula 1 is present in an amount of 0.0001 to 20 wt% relative to the total weight of the quasi-drug composition.

[0069] In the present invention, the above-mentioned pharmaceutical composition may have anti-atopic, antibacterial, cell-promoting or antioxidant activities.

[0070] The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable salt as needed in addition to the compound represented by the above chemical formula 1.

[0071] In addition to the above-mentioned ingredients, the quasi-drug composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent, as needed. The pharmaceutically acceptable carrier, excipient, or diluent is not limited as long as it does not impair the effects of the present invention, and may include, for example, fillers, bulking agents, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, fragrances, preservatives, etc.

[0072] Representative examples of pharmaceutically acceptable carriers, excipients or diluents of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, maltitol, starch, gelatin, glycerin, acacia gum, alginate, calcium phosphate, calcium carbonate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil, propylene glycol, polyethylene glycol, vegetable oil, injectable esters, withepsol, macrogol, Tween 61, cacao butter, lauric acid, etc.

[0073] The pharmaceutical composition of the present invention may include, but is not limited to, a disinfectant, a shower foam, an ointment, a wet tissue, a coating agent, etc., and the formulation method, dosage, method of use, components, etc. of the pharmaceutical composition may be appropriately selected from conventional techniques known in the art.

[0074] The present invention relates to the use of a novel compound for the preparation of a composition having anti-atopic activity, antibacterial activity, cell-promoting activity, and antioxidant activity.

[0075] The present invention relates to the use of a novel compound or a cosmetically acceptable salt thereof for the manufacture of a cosmetic composition having anti-atopic activity, antibacterial activity, cell-promoting activity, and antioxidant activity.

[0076] The present invention relates to the use of a novel compound or a pharmaceutically acceptable salt thereof for the manufacture of a pharmaceutical composition having anti-atopic activity, antibacterial activity, cell-promoting activity, and antioxidant activity.

[0077] In the present invention, the novel compound is represented by the above chemical formula 1, and the descriptions of anti-atopic activity, antibacterial activity, cell-promoting activity, antioxidant activity, cosmetically acceptable salt, and pharmaceutically acceptable salt are as described above.

[0078] Hereinafter, the present invention will be described in more detail by way of examples. However, the following examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following examples.

[0079]

[0080] Example 1: Preparation of 4-(nicotinoyloxy)benzylnicotinate

[0081] A compound represented by the following chemical formula 1 was prepared according to the following reaction scheme 1.

[0082] Specifically, Gastrodigenin (1.0 g, 1.0 eq) and anhydrous methylene chloride (10 ml) were placed in a reactor and cooled to 0-5°C under a nitrogen atmosphere. Triethylamine (1.8 g, 2.2 eq) was added, and nicotinoyl chloride (2.4 g, 2.1 eq) was slowly added over 10 minutes, followed by stirring at room temperature for more than 1 hour. After completion of the reaction, the reaction solution was extracted with methylene chloride (15 ml) and PW (20 ml), and the organic layer was concentrated under reduced pressure and separated by column chromatography with EtOAc / n-Hep as the developing solvent to obtain a compound represented by the following chemical formula 1 (2.2 g, yield 83.5%).

[0083] 1H-NMR (400MHz, DMSO-d6) δ 9.40 (s, 1H), 9.27 (s, 1H), 8.87-8.86 (dd,z 1H), 8.80-8.78 (dd, 1H), 8.47-8.44(dd, 1H), 8.35-8.32(dd, 1H), 7.57-7.55(m, 2H), 7.51-7.47(m, 1H), 7.43-7.40(m, 1H), 7.30-7.27(m,2H), 5.43 (s, 2H)

[0084] MS (ESI+): m / z 335.09 [M+H]+.

[0085] [Chemical Formula 1]

[0086]

[0087] [Reaction Formula 1]

[0088]

[0089]

[0090] Comparative Example 1

[0091] NA (Nicotinic acid) was purchased from Sigma-Aldrich and prepared.

[0092] Comparative Example 2

[0093] 4HBA (4-hydroxybenzyl alcohol) was purchased from Sigma-Aldrich and prepared.

[0094]

[0095] Experimental Example 1: Antibacterial

[0096] To measure the antibacterial activity of the novel compound (ATO-004) synthesized in Example 1, the following experiment was conducted.

[0097] Malassezia furfur (M furfur (KCTC 7743)) was obtained from the Biological Resource Center (KCTC) of the Korea Research Institute of Bioscience and Biotechnology, and the medium of M. furfur was cultured in an incubator at 37°C for 5-6 days using SDA (Difco, USA). The antibacterial activity of the novel compound (ATO-004) synthesized in the example was measured through an ager diffusion test. The concentration of each extract and fraction was adjusted to 40 mM on a paper disc (diameter 7 mm, Poshi kaisha. Ltd., Japan) and used in the experiment. 50 μl of the sample was slowly absorbed onto each paper and the solvent was evaporated through a drying process. The cultured strain was 1 × 10 7The concentration was adjusted to CFU / ml and used in the experiment. 100 μl of each strain was inoculated onto a plate medium and smeared using a sterile cotton swab. A paper disc, absorbed by each sample, was placed on the plate medium inoculated with the strain and cultured. Antibacterial activity was measured by the clear zone that appeared around the disc.

[0098] The novel compound (ATO-004) was treated at concentrations of 40 mM, 20 mM, 10 mM, and 5 mM. For comparison, NA (40 mM) of Comparative Example 1 and 4HBA (40 mM) of Comparative Example 2 were treated, and the results are shown in Fig. 1 and Table 1.

[0099]

[0100] Inhibition zone(mm)NA4HBAATO-00440mM20mM10mM5mMM.furfur--1515129

[0101] -: No antibacterial activity

[0102] - Well Size: 7mm

[0103]

[0104] Referring to FIG. 1 and Table 1, it can be confirmed that the novel compound (ATO-004) according to the present invention has excellent antibacterial activity, unlike NA and 4HBA.

[0105]

[0106] Experimental Example 2

[0107] In order to measure the cell proliferation ability of the novel compound (ATO-004) synthesized in Example 1, the following experiment was conducted. The following experiment was conducted using human epidermal cells (HaCaT) and human dermal fibroblasts (Hs68), and the results thereof are shown in Figures 2 and 3.

[0108] HaCaT and Hs68 were added to a 96-well plate at 1X10 per well each. 3After culturing for 24 hours, the cells were aliquoted at 100 μl and treated with different concentrations of the negative control group (Control; untreated group) and the novel compound (ATO-004). After 24 hours of treatment, the absorbance was measured at 450 nm using the CCK8 (Dojindo, CK04-13) reagent to confirm changes in cell activity.

[0109]

[0110] Referring to FIG. 2, it can be confirmed that the novel compound (ATO-004) according to the present invention has cell proliferation activity in a concentration-dependent manner compared to NA and 4HBA.

[0111]

[0112] Experimental Example 3

[0113] In order to measure the antioxidant activity of the novel compound (ATO-004) synthesized in Example 1, the following experiment was conducted. In order to examine the ability of the compound manufactured in Example 1 to inhibit the production of H2O2-induced reactive oxygen species, DCF-DA (Dichlorodihydrofluorescein Diacetate) staining was confirmed, and the results are shown in Figure 4 below. The experiment was conducted by seeding H2O2 cells in a 35pi dish at a density of 2x10 per dish. 5 Cells were seeded and cultured for 24 hours. Thereafter, the compound prepared in Example 1 was treated to the cells and cultured for an additional 24 hours. Ten minutes after loading with 5 mM DCF-DA, the cells were examined under a fluorescence microscope, and the number of cells expressing DCF-DA fluorescence was counted using Image J.

[0114]

[0115] Referring to FIG. 4, it was confirmed that in cells treated with the novel compound (ATO-004) according to the present invention, the increase in reactive oxygen species due to H2O2 treatment was significantly reduced compared to the positive control group (H2O2 treatment) and NA.

[0116]

[0117] Experimental Example 4

[0118] In order to measure the anti-atopic activity of the novel compound (ATO-004) synthesized in Example 1, the following experiment was conducted. HaCaT cells, an epidermal cell line, were seeded in a 6-well plate at a density of 15 х 10 per well. 4 After culturing the cells, the cells were treated with atopic inducers OVA (600 μg / mL) and rhTSLP (50 ng / mL) and cultured for 72 hours. The supernatant was removed, the cells were isolated, RNA was extracted, cDNA was synthesized, and IL-5 expression was confirmed through RT-PCR (qPCR).

[0119]

[0120] Referring to FIG. 5, it can be confirmed that the novel compound (ATO-004) according to the present invention can reduce the expression of IL-5, an atopic genetic material that appears in various stimuli, compared to NA.

[0121] A composition comprising a novel compound according to the present invention can exhibit excellent anti-atopic, cell proliferation, antioxidant and antibacterial activities.

Claims

1. An anti-atopic composition comprising a compound represented by the following chemical formula 1 or a salt thereof as an active ingredient. [Chemical Formula 1] 2. In paragraph 1, A composition, wherein the composition further has an antibacterial use.

3. In paragraph 1, A composition, wherein the composition further has a cell promoting use.

4. In paragraph 1, A composition, wherein the composition further has an antioxidant function.

5. A cosmetic composition for anti-atopic dermatitis comprising a compound represented by the following chemical formula 1 or a cosmetically acceptable salt thereof as an active ingredient. [Chemical Formula 1] 6. In paragraph 5, A cosmetic composition, wherein the cosmetic composition further has an antibacterial use.

7. In paragraph 5, A cosmetic composition, wherein the cosmetic composition further has a cell promoting use.

8. In paragraph 5, A cosmetic composition, wherein the cosmetic composition further has an antioxidant function.

9. An anti-atopic quasi-drug composition comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical Formula 1] 10. In paragraph 9, A pharmaceutical composition, wherein the above pharmaceutical composition additionally has an antibacterial use.

11. In paragraph 9, The above-mentioned pharmaceutical composition further has a cell promoting use.

12. In paragraph 9, A pharmaceutical composition, wherein the above pharmaceutical composition additionally has an antioxidant function.

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