Compositions containing novel compounds

Abstract

The present invention relates to a composition comprising a novel compound having antibacterial activity and whitening activity and a salt thereof as an active ingredient, wherein the present invention is a composition comprising a compound represented by the following chemical formula 1 or a salt thereof as an active ingredient. [Chemical Formula 1]

Description

Technology Field

[0001] The present invention relates to a composition comprising a novel compound having antibacterial activity and whitening activity. Background Technology

[0002] The rapid growth of the cosmetics market can actually be attributed to the rapid growth of the functional cosmetics market. Six years after the Functional Cosmetics Act of the Korea Food and Drug Administration came into effect and related products were approved, approximately 5,000 products have been approved, representing a tenfold increase compared to the 477 products approved in the first year. According to statistics by the Korea Cosmetic Association, functional cosmetics accounted for over 13% of the total cosmetics market as of 2004, serving as evidence that the domestic functional cosmetics market is expanding rapidly.

[0003] Meanwhile, interest in skin whitening is steadily increasing, influenced by the growing focus on health and beauty. As the preference for white skin rises due to skin damage caused by ultraviolet rays and people seek clearer, cleaner skin through transparent makeup, interest in methods to achieve skin whitening effects is intensifying.

[0004] Accordingly, the inventors of the present invention made diligent research efforts to discover a novel compound that ensures safety and exhibits enhanced whitening activity, and confirmed that a compound represented by Chemical Formula 1 not only has excellent whitening activity but also exhibits antibacterial activity, thereby completing the present invention. The problem to be solved

[0005] The problem that the present invention aims to solve is to provide a composition comprising a novel compound and a salt thereof as an active ingredient.

[0006] The problem that the present invention aims to solve is to provide a cosmetic composition comprising a novel compound and a salt thereof as an active ingredient.

[0007] The problem that the present invention aims to solve is to provide a quasi-drug composition comprising a novel compound and a salt thereof as an active ingredient. means of solving the problem

[0008] One embodiment 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.

[0009] [Chemical Formula 1]

[0010]

[0011] In the present invention, the composition may have antibacterial activity.

[0012] In the present invention, the composition may have whitening activity.

[0013] 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.

[0014] [Chemical Formula 1]

[0015]

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

[0017] In the present invention, the cosmetic composition may have whitening activity.

[0018] Another aspect of the present invention is a quasi-drug composition comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0019] [Chemical Formula 1]

[0020]

[0021] In the present invention, the quasi-drug composition may have antibacterial activity.

[0022] In the present invention, the above-mentioned quasi-drug composition may have whitening activity. Effects of the invention

[0023] A composition containing a novel compound according to the present invention can exhibit excellent antibacterial and whitening activity. Brief explanation of the drawing

[0024] FIG. 1 is 4-((( according to one embodiment of the present invention E This is a diagram showing the reaction scheme for the preparation of )-3-(3,4-dihydroxyphenyl)acryloyl)oxy)benzyl(E)-3-(3,4-dihydroxyphenyl)acrylate. Figure 2 is a diagram showing the antibacterial activity of a novel compound (ATO-001). Figure 3 is a graph showing the whitening activity of the novel compound (ATO-001). Specific details for implementing the invention

[0025] 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 embodied in various different forms and is not limited to the embodiments described herein.

[0027] One embodiment 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.

[0028] [Chemical Formula 1]

[0029]

[0030] In addition, the novel compound according to Formula 1 of the present invention is as a starting material ( E )-3-(3,4-dihydroxyphenyl)acrylic acid(( E It can be manufactured through a step of reacting )-3-(3,4-dihydroxyphenyl)acrylic acid).

[0031] In the present invention, the compound represented by Formula 1 is preferably 0.0001 to 20 weight% of the total weight of the composition.

[0032] In the present invention, the composition may have antibacterial activity or whitening activity.

[0033] In the present invention, the antibacterial activity is acne bacteria ( Cutibacterium acnes ATCC 6919) and athlete's foot fungus ( Trichophyton rubrum It was confirmed through ATCC 28188), and whitening activity was confirmed through the Melanin Contents Assay method, which measures melanin production induced by α-MSH.

[0035] Another aspect of the present invention is a cosmetic composition comprising a compound represented by the above formula 1 or a cosmetically acceptable salt thereof as an active ingredient.

[0036] In the cosmetic composition according to the present invention, the compound represented by Chemical Formula 1 is preferably 0.0001 to 20 weight% based on the total weight of the cosmetic composition.

[0037] In the present invention, the cosmetic composition may have antibacterial activity or whitening activity.

[0038] The cosmetic composition of the present invention may include, without limitation, commonly accepted ingredients in addition to the compound represented by Formula 1, and may include, for example, conventional auxiliary agents such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances, and carriers.

[0039] The cosmetic composition according to the present invention may be prepared in one or more formulations selected from the group consisting of solutions, topical ointments, creams, foams, nourishing lotions, softening lotions, packs, softening waters, emulsions, makeup bases, essences, soaps, liquid cleansers, bath additives, sunscreen creams, sun oils, suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansing products, oils, powder foundations, emulsion foundations, wax foundations, patches, and sprays, but is not limited thereto.

[0040] In addition, the cosmetic composition of the present invention may further include one or more cosmetically acceptable carriers that are incorporated into general skin cosmetics, and may appropriately incorporate, for example, oils, water, surfactants, moisturizers, lower alcohols, thickeners, chelating agents, pigments, preservatives, fragrances, etc., as conventional ingredients, but are not limited thereto. The cosmetically acceptable carriers included in the cosmetic composition of the present invention vary depending on the formulation.

[0041] In the case where the formulation of the present invention is an ointment, paste, cream, or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, or a mixture thereof may be used as a carrier component.

[0042] In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or a mixture thereof may be used as a carrier component, and in particular, in the case of a spray, it may additionally include a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0043] When the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent, or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, and in particular, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan may be used.

[0044] In the case where the formulation of the present invention is a suspension, liquid diluents such as water, ethanol, or propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant, etc. may be used as carrier components.

[0045] In the case where the formulation of the present invention is soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolyzates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars, etc. may be used as carrier components.

[0046] In the case where 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, sarcocitate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester, etc. may be used as a carrier component.

[0048] Another aspect of the present invention is a quasi-drug composition comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0049] In the quasi-drug composition according to the present invention, the compound represented by Chemical Formula 1 is preferably 0.0001 to 20 weight% of the total weight of the quasi-drug composition.

[0050] In the present invention, the quasi-drug composition may have antibacterial activity or whitening activity.

[0051] The quasi-drug composition of the present invention may further include, in addition to the compound represented by Chemical Formula 1, a pharmaceutically acceptable salt as needed.

[0052] The quasi-drug composition of the present invention may further include, in addition to the above components, 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, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, fragrances, preservatives, etc.

[0053] 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, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, propylene glycol, polyethylene glycol, vegetable oil, injectable esters, Witepsol, macrogol, Tween 61, cocoa dough, laurize, etc.

[0054] Examples of the quasi-drug composition of the present invention include, but are not limited to, disinfectant cleansers, shower foams, ointment liquids, wet wipes, coating agents, etc., and the formulation method, dosage, method of use, components, etc. of the quasi-drug may be appropriately selected from ordinary techniques known in the technical field.

[0056] The present invention will be explained in more detail below through examples. However, the following examples are merely illustrative of the present invention, and the scope of the present invention is not limited to the following examples.

[0058] Preparation Example 1: (E)-3-(3,4- Diacetoxyphenyl )acryl Acid (( E Preparation of )-3-(3,4-diacetoxyphenyl)acrylic acid)

[0059] ( E)-3-(3,4-dihydroxyphenyl)acrylic acid(( E )-3-(3,4-dihydroxyphenyl)acrylic acid)(3.0 g, 1.0 eq) and pyridine (1.97 ml, 1.5 eq) were added to a reactor and cooled from room temperature to 0–5°C. Acetic anhydride (8.5 g, 5.0 eq) was slowly added over 10–20 minutes at the same temperature, followed by stirring at room temperature for more than 18 hours. Methylene chloride (10 ml) and n-heptane ( n -Heptane)(30 ml) was added and stirred at room temperature for more than 1 hour. The solid compound was filtered and then vacuum dried at 40°C for more than 12 hours to obtain a compound according to Chemical Formula 2 below (3.5 g, yield 79.7%).

[0060] [Chemical Formula 2]

[0061]

[0064] Preparation Example 2: 4 -(( E )-3-((4-((( E )-3-(3,4- Diacetoxyphenyl )Acryloil) Oxy ) benzyl )oxy)-3-oxoprobe-1-en-1-yl)-1,2-phenylene Diacetate (4-(( E )-3-((4-((( E )-3-(3,4-diacetoxyphenyl)acryloyl)oxy)benzyl)oxy)-3-oxoprop-1-en-1-yl)-1,2-phenylene diacetate Manufacturing of )

[0065] The product prepared in the above Preparation Example 1 ( E)-3-(3,4-diacetoxyphenyl)acrylic acid (1.7 g, 2.1 eq) was placed in a reactor and cooled to 0–5°C under a nitrogen atmosphere. Thionyl chloride (SOCl2) (3.4 ml, excess) was slowly added and stirred at room temperature for more than 1 hour. After concentrating the thionyl chloride under reduced pressure, anhydrous methylene chloride (10 ml) was added under a nitrogen atmosphere (Reactor A). Gastrodigenin (Illdrich) (0.4 g, 1.0 eq), anhydrous methylene chloride (5 ml), and triethylamine (0.7 g, 2.2 eq) were added to Reactor B and stirred at room temperature for more than 30 minutes. After the materials from Reactor A were slowly added to Reactor B at room temperature for 10–20 minutes, the mixture was refluxed and stirred for more than 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and then separated by column chromatography using ethyl acetate / n-heptane as the developing solvent to obtain a compound according to the following chemical formula 3 (1.1 g, yield 55.5%).

[0066] [Chemical Formula 3]

[0067]

[0068] 1 H-NMR (400MHz, DMSO- d6 ) δ 7.84-7.68 (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).

[0070] Examples 1 : 4 -((( E )-3-(3,4- dihydroxyphenyl )Acryloil) Oxy ) benzyl ( E )-3-(3,4-dihydroxyphenyl)acrylate(4-((( E )-3-(3,4-dihydroxyphenyl)acryloyl)oxy)benzyl ( E )-3-(3,4- dihydroxyphenyl ) acrylate Manufacturing of )

[0071] Fig. 1 is 4-((( E )-3-(3,4-dihydroxyphenyl)acryloyl)oxy)benzyl ( E This is a diagram showing the reaction scheme for the preparation of )-3-(3,4-dihydroxyphenyl)acrylate.

[0072] 4-(( prepared in Preparation Example 2 above E )-3-((4-((( E 0.5 g (1 eq) of )-3-(3,4-diacetoxyphenyl)acryloyl)oxy)benzyl)oxy)-3-oxoprobe-1-en-1-yl)-1,2-phenylene diacetate and 5 ml of 1,4-dioxane were placed in a reactor, 2.0 ml (5 eq) of 2N sodium hydroxide (NaOH) was added, and the mixture was stirred at 50°C for at least 3 hours. After the reaction was complete, the mixture was cooled to room temperature, 10 ml of 10% hydrochloric acid (HCl) and 15 ml of ethyl acetate were added, and the mixture was stirred for at least 30 minutes. The organic layer was extracted, dehydrated with magnesium sulfate (MgSO4), and concentrated under reduced pressure. The mixture was vacuum dried at 40°C for at least 10 hours to obtain the compound according to Chemical Formula 1 (0.18 g, yield 50.0%).

[0073] [Chemical Formula 1]

[0074]

[0075] 1 H-NMR (400MHz, DMSO- d6 ) δ 7.70-7.66 (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),

[0076] MS (ESI+): m / z 449.12 [M+H] + .

[0078] Comparative example 1

[0079] Caffeic acid was purchased from Sigma-Aldrich and prepared.

[0081] Comparative example 2

[0082] 4HBA (4-hydroxybenzyl alcohol) was purchased from Sigma-Aldrich and prepared.

[0084] Comparative example 3

[0085] I purchased and prepared NC (Negative control; Alpha-MSH) from Sigma-Aldrich.

[0087] Comparative example 4

[0088] PC (positive control; arbutin) was purchased from Sigma-Aldrich and prepared.

[0090] Experimental example 1

[0091] To measure the antibacterial activity of the compound (ATO-001) prepared in Example 1, the following experiment was conducted.

[0092] Acne bacteria Cutibacterium acnes ATCC 6919) and athlete's foot fungus ( Trichophyton rubrum ATCC 28188) was 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 Figure 2 and Table 1.

[0093] division Inhibition zone size (mm) Cutibacterium acnes ATCC 6919 Trichophyton rubrum ATCC 28188 1 Negative control - - 2 Comparative Example 1 - - 3 Comparative Example 2 - - 4 Example 1 12 (mm) 15 (mm)

[0094] Well size: 7 mm

[0096] Referring to Table 1 and Figure 2 above, it can be seen that the compound prepared in Example 1 exhibits high antibacterial activity, unlike Comparative Examples 1 and 2.

[0098] Experimental example 2

[0099] To measure the whitening activity of the compound (ATO-001) prepared in the example, the Melanin Contents Assay method, which measures melanin production induced by α-MSH, was used.

[0100] Specifically, 2 × 10⁶ B16F10 melanoma cells in a 48-well plate 4 The samples were added at the specified concentration and treated after 24 hours in DMEM medium containing 10% FBS and 1% penicillin / streptomycin. There were a total of 6 sample groups: a control, a negative control, three sample concentrations (0.5 ppm, 1 ppm, 2 ppm), and a positive control. Only clear full media was used for the control, while for the NC, sample groups, and PC, 40 μM α-MSH was added to clear full media diluted 200-fold to 0.2 μM.

[0101] To adjust the volume, 1 / 200 of the required amount of clear full media (DMSO) was added to the control and NC, while 1 / 200 of the required amount of the substance and 10,000 ppm of arbutin were added to the substance group and PC. Cells were treated with 600 μL aliquots, as in seeding, and incubated for 48 hours. Afterward, the supernatant was removed, and the cells were washed twice with 1xPBS. Then, 200 μL of RIPA buffer (1% inhibitor cocktail) was added, and the mixture was incubated at 4°C for 30 minutes before the cells were collected into 1.5 ml e-tubes. Cells were centrifuged in a deep freezer centrifuge at 15,000 rpm at -8°C for 20 minutes to remove the supernatant, and the pellet was collected. Then, 500 µl of 1N NaOH was added and the pellet was dissolved at 70°C for 1 hour. Afterward, 100 µl of the dissolved pellet was placed into 96-well plates, and the absorbance was measured at 475 nm using a microplate reader.

[0102] The whitening efficacy was evaluated using absorbance measurements, and the results are shown in Figure 3.

[0104] Referring to Figure 3, in the case of the compound prepared in Example 1, it can be seen that the melanin content gradually decreases significantly with increasing treatment concentration at concentrations of 1 ppm and 2 ppm.

[0106] As such, it can be confirmed that the novel compound represented by Chemical Formula 1 according to the present invention exhibits excellent antibacterial and whitening activity.

Claims

Claim 1 A functional cosmetic composition comprising a compound represented by the following chemical formula 1 or a cosmetically acceptable salt thereof in an amount of 0.0001% to 20% by weight, which inhibits the proliferation of acne bacteria (Cutibacterium acnes) and athlete's foot fungi (Trichophyton rubrum) while simultaneously reducing melanin production induced by α-MSH. [Chemical Formula 1] Claim 2 A cosmetic composition according to claim 1, wherein the compound represented by Chemical Formula 1 forms a growth inhibition ring of 10 mm or more against Trichophyton rubrum. Claim 3 A cosmetic composition according to claim 1, wherein the reduction in melanin production comprises a concentration-dependent decrease in melanin content in B16F10 melanoma cells under α-MSH treatment conditions. Claim 4 A functional quasi-drug composition comprising a compound represented by the following Chemical Formula 1 or a cosmetically acceptable salt thereof in an amount of 0.0001% to 20% by weight, which inhibits the proliferation of acne bacteria (Cutibacterium acnes) and athlete's foot fungi (Trichophyton rubrum) while simultaneously reducing melanin production induced by α-MSH. [Chemical Formula 1] Claim 5 In claim 4, the compound represented by Chemical Formula 1 is a quasi-drug composition that forms a growth inhibition ring of 10 mm or more against Trichophyton rubrum. Claim 6 A quasi-drug composition according to claim 4, wherein the reduction in melanin production comprises a concentration-dependent decrease in melanin content in B16F10 melanoma cells under α-MSH treatment conditions. Claim 7 delete Claim 8 delete Claim 9 delete

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