Composition comprising novel compound

Abstract

The present invention relates to a composition comprising, as an active ingredient, a novel compound having antibacterial activity and whitening activity and a salt thereof. The present invention is 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. 2024-0026602, 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 antibacterial activity and whitening activity.

[0004] The rapid growth of the cosmetics market can in fact be attributed to the rapid growth of the functional cosmetics market. In just six years since the Ministry of Food and Drug Safety's Functional Cosmetics Act came into effect and related products were approved, approximately 5,000 functional cosmetics products have been approved, representing a tenfold increase from the 477 products approved in the first year. According to statistics from the Korea Cosmetic Association, functional cosmetics accounted for over 13% of the total cosmetics market as of 2004, demonstrating the rapid expansion of the domestic functional cosmetics market.

[0005] Meanwhile, interest in skin whitening is growing, driven by the growing trend toward health and beauty. The preference for a fair complexion is growing due to factors such as UV damage, and the pursuit of clearer, cleaner skin through transparent makeup is fueling interest in methods for achieving skin whitening effects.

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

[0007] The problem to be solved by the present invention is to provide a composition comprising a novel compound and its salt as an effective ingredient.

[0008] The problem to be solved by the present invention is to provide a cosmetic composition comprising a novel compound and its salt as an active ingredient.

[0009] The problem to be solved by the present invention is to provide a pharmaceutical composition comprising a novel compound and its salt as an active ingredient.

[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 antibacterial activity.

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

[0015] 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.

[0016] [Chemical Formula 1]

[0017]

[0018] In the present invention, the cosmetic composition may have antibacterial activity.

[0019] In the present invention, the cosmetic composition may have whitening activity.

[0020] 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.

[0021] [Chemical Formula 1]

[0022]

[0023] In the present invention, the above-mentioned pharmaceutical composition may have antibacterial activity.

[0024] In this case, the above-mentioned pharmaceutical composition may have whitening activity.

[0025] The present invention relates to the use of a novel compound for the preparation of a composition having antibacterial activity and whitening activity.

[0026] The present invention relates to the use of a novel compound or a cosmetically acceptable salt thereof for the production of a cosmetic composition having antibacterial activity and whitening activity.

[0027] 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 antibacterial activity and whitening activity.

[0028] A composition comprising a novel compound according to the present invention can exhibit excellent antibacterial and whitening activities.

[0029] FIG. 1 is a drawing showing a reaction scheme for producing 4-(((E)-3-(3,4-dihydroxyphenyl)acryloyl)oxy)benzyl(E)-3-(3,4-dihydroxyphenyl)acrylate according to one embodiment of the present invention.

[0030] Figure 2 is a drawing showing the antibacterial activity of a novel compound (ATO-001).

[0031] Figure 3 is a graph showing the whitening activity of a novel compound (ATO-001).

[0032] 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.

[0033]

[0034] 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.

[0035] [Chemical Formula 1]

[0036]

[0037] In addition, the novel compound according to the chemical formula 1 of the present invention can be prepared through a step of reacting (E)-3-(3,4-dihydroxyphenyl)acrylic acid as a starting material.

[0038] In the present invention, it is preferable that the compound represented by the above chemical formula 1 is 0.0001 to 20 wt% based on the total weight of the composition.

[0039] In the present invention, the composition may have antibacterial activity or whitening activity.

[0040] In the present invention, antibacterial activity was confirmed through Cutibacterium acnes ATCC 6919 and Trichophyton rubrum ATCC 28188, and whitening activity was confirmed through the Melanin Contents Assay method that measures melanin production induced by α-MSH.

[0041]

[0042] Another aspect of the present invention is a cosmetic composition comprising a compound represented by the above chemical formula 1 or a cosmetically acceptable salt thereof as an active ingredient.

[0043] 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.

[0044] In the present invention, the cosmetic composition may have antibacterial activity or whitening activity.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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.

[0054]

[0055] Another aspect of the present invention is a pharmaceutical composition comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0056] 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.

[0057] In the present invention, the above-mentioned pharmaceutical composition may have antibacterial activity or whitening activity.

[0058] 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.

[0059] 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.

[0060] 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.

[0061] 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.

[0062] The present invention relates to the use of a novel compound for the preparation of a composition having antibacterial activity and whitening activity.

[0063] The present invention relates to the use of a novel compound or a cosmetically acceptable salt thereof for the production of a cosmetic composition having antibacterial activity and whitening activity.

[0064] 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 antibacterial activity and whitening activity.

[0065] In the present invention, the novel compound is represented by the above chemical formula 1, and the descriptions of antibacterial activity, whitening activity, cosmetically acceptable salt, and pharmaceutically acceptable salt are as described above.

[0066] 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.

[0067]

[0068] Manufacturing Example 1: Manufacturing of (E)-3-(3,4-diacetoxyphenyl)acrylic acid

[0069] (E)-3-(3,4-dihydroxyphenyl)acrylic acid (3.0 g, 1.0 eq) and pyridine (1.97 ml, 1.5 eq) were placed in a reactor and cooled from room temperature to 0 to 5°C. Acetic anhydride (8.5 g, 5.0 eq) was slowly added at the same temperature over 10 to 20 minutes, and then stirred at room temperature for more than 18 hours. Methylene chloride (10 ml) and n-heptane (30 ml) were added to the reaction solution and stirred at room temperature for more than 1 hour. The solid compound was filtered and dried under vacuum at 40°C for more than 12 hours to obtain a compound (3.5 g, yield 79.7%) according to the following chemical formula 2.

[0070] [Chemical Formula 2]

[0071]

[0072]

[0073] Manufacturing Example 2: Manufacturing of 4-((E)-3-((4-(((E)-3-(3,4-diacetoxyphenyl)acryloyl)oxy)benzyl)oxy)-3-oxoprop-1-en-1-yl)-1,2-phenylenediacetate

[0074] (E)-3-(3,4-diacetoxyphenyl)acrylic acid (1.7 g, 2.1 eq) prepared in the above Preparation Example 1 was placed in a reactor and cooled to 0 to 5°C under a nitrogen atmosphere. Thionyl chloride (SOCl2) (3.4 ml, exess) was slowly added and stirred at room temperature for more than 1 hour. Thionyl chloride was concentrated under reduced pressure and then anhydrous methylene chloride (10 ml) was added under a nitrogen atmosphere (reactor A). Gastrodigenin (Ildrich) (0.4 g, 1.0 eq), anhydrous methylene chloride (5 ml), and triethylamine (0.7 g, 2.2 eq) were placed in reactor B and stirred at room temperature for more than 30 minutes. After the material in reactor A was slowly added to reactor B at room temperature over 10 to 20 minutes, the mixture was stirred under reflux for more than 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure and separated by column chromatography using ethyl acetate / n-heptane as a developing solvent to obtain a compound (1.1 g, yield 55.5%) according to the following chemical formula 3.

[0075] [Chemical Formula 3]

[0076]

[0077] 1 H-NMR (400MHz, DMSO-d6) δ7.84-7.68 (m, 6H), 7.52-7.50 (d, 2H), 7.38-7.31 (m, 2H), 7.26-7.23 (d, 2H), 6.92-6.88 (d, 1H), 6.75-6.71 (d, 1H), 5.25 (s, 2H), 2.31-2.28 (m, 12H).

[0078]

[0079] Example 1: Preparation of 4-(((E)-3-(3,4-dihydroxyphenyl)acryloyl)oxy)benzyl (E)-3-(3,4-dihydroxyphenyl)acrylate

[0080] Figure 1 is a drawing showing a reaction scheme for preparing 4-(((E)-3-(3,4-dihydroxyphenyl)acryloyl)oxy)benzyl (E)-3-(3,4-dihydroxyphenyl)acrylate.

[0081] 4-((E)-3-((4-(((E)-3-(3,4-diacetoxyphenyl)acryloyl)oxy)benzyl)oxy)-3-oxoprob-1-en-1-yl)-1,2-phenylene diacetate (0.5 g, 1 eq) prepared in the above Preparation Example 2 and 5 ml of 1,4-dioxane were placed in a reactor, 2N sodium hydroxide (NaOH) (2.0 ml, 5 eq) was added, and the mixture was stirred at 50°C for 3 hours or more. After completion of the reaction, the mixture was cooled to room temperature, 10% hydrochloric acid (HCl) (10 ml) and ethyl acetate (15 ml) were added, and the mixture was stirred for 30 minutes or more. The organic layer was extracted, dehydrated with magnesium sulfate (MgSO4), and concentrated under reduced pressure. A compound according to chemical formula 1 (0.18 g, yield 50.0%) was obtained by vacuum drying at 40°C for more than 10 hours.

[0082] [Chemical Formula 1]

[0083]

[0084] 1 H-NMR (400MHz, DMSO-d6) δ7.70-7.66 (d, 1H), 7.55-7.51 (d, 1H), 7.49-7.47 (d, 2H), 7.21-7.19 (d, 2H), 7.14-7.01 (m, 4H), 6.80-6.75 (m, 2H), 6.51-6.47 (d, 1H), 6.35-6.31 (d, 1H),

[0085] MS (ESI+): m / z 449.12 [M+H] + .

[0086]

[0087] Comparative Example 1

[0088] Caffeic acid (purchased from Sigma-Aldrich) was prepared.

[0089]

[0090] Comparative Example 2

[0091] 4HBA (4-hydroxybenzly alcohol) was purchased and prepared from Sigma-Aldrich.

[0092]

[0093] Comparative Example 3

[0094] NC (Negative control; Alpha-MSH) was purchased and prepared from Sigma-Aldrich.

[0095]

[0096] Comparative Example 4

[0097] PC (positive control; arbutin) was purchased and prepared from Sigma-Aldrich.

[0098]

[0099] Experimental Example 1

[0100] To measure the antibacterial activity of the compound (ATO-001) manufactured in Example 1, the following experiment was conducted.

[0101] Cutibacterium acnes (ATCC 6919) and Trichophyton rubrum (ATCC 28188) were cultured and treated with the novel compound (ATO-001) at a concentration of 40 mM each. For comparison, caffeic acid of Comparative Example 1 and 4HBA of Comparative Example 2 were treated at a concentration of 40 mM each, and the results are shown in Fig. 2 and Table 1.

[0102] Inhibition zone size (mm) Cutibacterium acnes ATCC 6919 Trichophyton rubrum ATCC 281881 Negative control--2 Comparative example 1--3 Comparative example 2--4 Example 1 12 (mm) 15 (mm)

[0103] Well size: 7 mm

[0104]

[0105] Referring to Table 1 and Figure 2 above, it can be confirmed that the compound prepared in Example 1 exhibits high antibacterial activity, unlike Comparative Examples 1 and 2.

[0106]

[0107] Experimental Example 2

[0108] To measure the whitening activity of the compound (ATO-001) manufactured in the example, the Melanin Contents Assay method, which measures melanin production induced by α-MSH, was used.

[0109] Specifically, B16F10 melanoma cells were seeded at 2 × 10 in a 48-well plate. 4 The samples were treated after 24 hours in DMEM medium containing 10% FBS and 1% penicillin / streptomycin. The sample groups were divided into 6 groups: control, negative control, 3 sample concentrations (0.5 ppm, 1 ppm, 2 ppm), and positive control. Only clear full media was used for the control, and for NC, sample groups, and PC, 40 μM α-MSH was used in clear full media diluted 200-fold to 0.2 μM.

[0110] To adjust the volume, DMSO (1 / 200 of the required clear full media) was added to the control and NC, and 1 / 200 of the required clear full media and 10,000 ppm arbutin were added to the material group and PC. Cells were treated with 600 μL each in the same amount as when seeding and incubated for 48 hours. After removing the supernatant, the cells were washed twice with 1x PBS, and 200 μL of RIPA buffer (1% inhibitor cocktail) was added and reacted at 4°C for 30 minutes. The cells were then collected in a 1.5 ml e-tube. The cells were centrifuged in a deep freezer centrifuge at 15,000 rpm, -8℃ for 20 minutes, the supernatant was removed, and only the pellet was collected. 500 ul of 1N NaOH was added and dissolved at 70℃ for 1 hour. 100 ul of the dissolved pellet was placed in each 96-well plate, and the absorbance was measured at 475 nm using a microplate reader.

[0111] The whitening efficacy was evaluated through absorbance measurements, and the results are shown in Figure 3.

[0112]

[0113] Referring to FIG. 3, in the case of the compound manufactured in Example 1, it can be confirmed that the melanin content gradually significantly decreases as the treatment concentration increases at concentrations of 1 ppm and 2 ppm.

[0114]

[0115] It can be confirmed that the novel compound represented by chemical formula 1 according to the present invention exhibits excellent antibacterial and whitening activities.

Claims

1. A 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 having antibacterial activity.

3. In paragraph 1, A composition having whitening activity.

4. A cosmetic composition comprising a compound represented by the following chemical formula 1 or a cosmetically acceptable salt thereof as an active ingredient. [Chemical Formula 1] 5. In paragraph 4, A cosmetic composition having antibacterial activity.

6. In paragraph 4, A cosmetic composition having whitening activity.

7. A pharmaceutical composition comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical Formula 1] 8. In paragraph 7, The above-mentioned pharmaceutical composition has antibacterial activity.

9. In paragraph 7, The above-mentioned pharmaceutical composition has whitening activity.

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