KR20210066746A - A novel constituent derived from Aralia cordata and uses thereof - Google Patents

Abstract

The present disclosure relates to novel lignan compounds derived from Aralia cordata and uses thereof, and specifically, to novel lignan compounds isolated and purified from Aralia cordata and an antioxidant composition comprising the same. The composition according to the present disclosure can be usefully used as a pharmaceutical, food and cosmetic material.

Description

A novel constituent derived from Aralia cordata and uses thereof

It relates to a novel lignan compound isolated from poison ivy extract and an antioxidant composition comprising the same as an active ingredient.

Free radicals are generated in normal or pathological cell metabolism by external factors such as foreign substances or UV irradiation. When the human body uses oxygen for respiration and combustion, molecular oxygen readily reacts with free radicals to superoxide (·O ₂ -), hydrogen peroxide (H ₂ O ₂ ), hydroxyl radical (·OH), singlet oxygen ( ¹ O2), an alkyl radical (R0·), reactive oxygen species (ROS) containing peroxy radicals (R00·), and reactive nitrogen species containing ^{peroxynitrite (ONOO - )} species, RNS). These ROS and RNS act as excellent oxidizing and nitrifying agents, damaging major components in the human body, for example, lipids, proteins, nucleic acids and DNA, causing inflammation or lesions in many organs.

In particular, it is known that about 90% of modern diseases are related to free radicals, and specifically, these active species are related to diseases such as cancer, diabetes, stroke, myocardial infarction, Parkinson's disease, arteriosclerosis, rheumatoid arthritis, and allergies. known to be the cause.

Dokhwal is the root of durreup or yepdurup. Blackberry is a perennial herbaceous plant belonging to the Araliaceae family. It is a plant that is wild or cultivated in Japanese nests in Korea, China, and Japan. Its poisonous extract is a herbal medicine that has been used to treat pain, edema, fever, toothache, arthritis, etc., and young leaves and stems It is a popular vegetable because of its unique fragrance and is a useful plant resource that is also exported overseas. In particular, poison activity is known to have effects such as antioxidant action, platelet aggregation inhibitory action, or antipyretic action.

Therefore, it is necessary to isolate the compound from the poisonous activity with various effects and present it as a lead or candidate for antioxidant drugs.

According to one embodiment of the present disclosure, it relates to novel lignan compounds isolated from poisonous activity and uses thereof.

According to another embodiment, to provide an antioxidant pharmaceutical composition, a food composition, a health functional food composition or a cosmetic composition comprising the compound, an isomer, a solvate or a pharmaceutically acceptable salt thereof.

According to an embodiment of the present disclosure,

A compound represented by the following formula (1), an isomer, a solvate, or a pharmaceutically acceptable salt thereof is provided.

[Formula 1]

The R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are each independently hydrogen, a hydroxyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a carbonyl group (-CO-R ₇ ) , a carboxyl group (-CO-OR ₇ ), an alcohol group having 1 to 6 carbon atoms, or a substituted or unsubstituted phenylpropanoid group (C6C3),

R ₇ is hydrogen, a hydroxyl group, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms.

According to another embodiment of the present disclosure,

There is provided a pharmaceutical composition, a food composition, a health functional food composition or a cosmetic composition for antioxidants comprising the compound, an isomer, a solvate, or a pharmaceutically acceptable salt thereof.

The compound represented by Formula 1 of the present disclosure, an isomer, a solvate or a pharmaceutically acceptable salt thereof has an excellent antioxidant effect by rapidly removing oxidizing radicals.

In addition, it is possible to provide a pharmaceutical composition for antioxidants comprising the compound represented by Formula 1, an isomer, a solvate or a pharmaceutically acceptable salt thereof, a health functional food for antioxidants or a cosmetic composition for antioxidants comprising the same.

1 is a schematic diagram showing a process for obtaining extracts and fractions from poison activity as a process for isolating novel compounds of the present disclosure.
2 is a schematic diagram showing a process for isolating a novel compound of the present disclosure from an ethyl acetate fraction obtained from poison activity.
^{3 is a schematic of 1} H-NMR of a novel lignan compound of the present disclosure.
^{4 is a schematic of 13} C-NMR of a novel lignan compound of the present disclosure.
5 is a schematic diagram of the HSQC spectrum of the novel lignan compound of the present disclosure.
6 is a schematic diagram of the HMBC spectrum of the novel lignan compound of the present disclosure.
7 is a schematic diagram of the high-resolution mass spectrometer spectrum of the novel lignan compound of the present disclosure and the corresponding exact mass value of the novel ionized lignan.
^{8 is a schematic diagram of 1} H-NMR of a lignan represented by Chemical Formula 3 isolated from poison activity.
^{9 is a schematic diagram of 13} C-NMR of a lignan represented by Chemical Formula 3 isolated from poison activity.
10 is a schematic diagram of the use-dependent ABTS radical scavenging ability of 8-O-4-dehydrocoumaroyl-ferulic acid.

The present disclosure can all be achieved by the following description. It is to be understood that the following description describes embodiments of the present disclosure, and the present disclosure is not necessarily limited thereto. In addition, it should be understood that the accompanying drawings are provided to aid understanding, and the present disclosure is not limited thereto.

The embodiments of the present disclosure may be subjected to various modifications and may be embodied in various forms. Accordingly, it is to be understood as including all modifications, equivalents and substitutions within the scope in which the spirit and technical features of the present disclosure are equivalent.

Unless otherwise specified, all numbers used in this disclosure are to be understood as modifying the term "about" in all instances. The modifier "about" is intended to have a generally recognized approximate meaning, which can be more accurately interpreted as a meaning within a specific percentage of the modified value, and more specifically, ±20%, ±10%, ± 5%, ±2% or ±1% or less.

Terms used in the present disclosure may be defined as follows. Terms not defined in the present disclosure may be defined in a range that can be commonly understood or learned in the technical field to which the present invention pertains.

“Alkyl group” may mean a monovalent group derived from a straight-chain or branched saturated hydrocarbon, and may be substituted or unsubstituted. Examples of such an alkyl group having 1 to 6 carbon atoms include methyl (Me, -CH ₃ ), ethyl (Et, -CH ₂ CH ₃ ), 1-propyl (n-Pr, n-propyl, -CH ₂ CH ₂ CH ₃ ) , 2-propyl (i-Pr, i-propyl, -CH(CH ₃ ) ₂ ), 1-butyl (n-Bu, n-butyl, -CH ₂ CH ₂ CH ₂ CH ₃ ), 2-methyl-1 -Propyl (i-Bu, i-butyl, -CH ₂ CH(CH ₃ ) ₂ ), 2-butyl (s-Bu, s-butyl, -CH(CH ₃ )CH ₂ CH ₃ ), 2-methyl- 2-propyl (t-Bu, t-butyl, -C(CH ₃ ) ₃ ), 1-pentyl (n-pentyl, -CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-pentyl (-CH(CH ₃ )CH ₂ CH ₂ CH ₃ ), 3-pentyl(-CH(CH ₂ CH ₃ ) ₂ ), 2-methyl-2-butyl(-C(CH ₃ ) ₂ CH ₂ CH ₃ ), 3-methyl- 2-Butyl(-CH(CH ₃ )CH(CH ₃ ) ₂ ), 3-methyl-1-butyl(-CH ₂ CH ₂ CH(CH ₃ ) ₂ ), 2-methyl-1-butyl(-CH _{2 )} CH(CH ₃ )CH ₂ CH ₃ ), 1-hexyl(-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-hexyl(-CH(CH ₃ )CH ₂ CH ₂ CH ₂ CH ₃ ), 3-Hexyl(-CH(CH ₂ CH ₃ )(CH ₂ CH ₂ CH ₃ )), 2-methyl-2-pentyl(-C(CH ₃ ) ₂ CH ₂ CH ₂ CH ₃ ), 3-methyl-2 -pentyl(-CH(CH ₃ )CH(CH ₃ )CH ₂ CH ₃ ), 4-methyl-2-pentyl(-CH(CH ₃ )CH ₂ CH(CH ₃ ) ₂ ), 3-methyl-3- pentyl(-C(CH ₃ )(CH ₂ CH ₃ ) ₂ ), 2-methyl-3-pentyl(-CH(CH ₂ CH ₃ )CH(CH ₃ ) ₂ ), 2,3-dimethyl-2-butyl (-C(CH ₃ ) ₂ CH(CH ₃ ) ₂ ) and 3,3-dimethyl-2-butyl(-CH(CH ₃ )C(CH ₃ ) ₃ , but these are exemplary only, and alkyl groups of the present disclosure is not limited to 1 to 6 carbon atoms.

"Alkoxy group" is a monovalent group having an -O-alkyl group, and may be understood to include all of a straight-chain, branched-chain or cyclic structure. The alkyl group includes all the alkyl groups defined above, and the alkyl group may be substituted or unsubstituted. Examples of such an alkoxy group include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, isobutoxy, and the like.

According to one embodiment of the present disclosure, a compound represented by the following Chemical Formula 1, an isomer, a solvate, or a pharmaceutically acceptable salt thereof may be provided.

According to another embodiment, there may be provided a pharmaceutical composition for antioxidants comprising a compound represented by the following Chemical Formula 1, an isomer, a solvate, or a pharmaceutically acceptable salt thereof.

[Formula 1]

The R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are each independently hydrogen, a hydroxyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a carbonyl group (-CO-R ₇ ) , a carboxyl group (-CO-OR ₇ ), an alcohol group having 1 to 6 carbon atoms, or a substituted or unsubstituted phenylpropanoid group (C6C3),

R ₇ may be hydrogen, a hydroxyl group, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms.

According to another embodiment, the R ₁ , R ₂ , R ₃ , R ₄ and R ₅ may each independently be hydrogen, a hydroxyl group, or an alkoxy group having 1 to 6 carbon atoms, wherein R ₆ is hydrogen, a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms, or a substituted phenylpropa group It may be a node.

Specifically, the phenylfrapanoid may be coumaric acid or ferulic acid in cis or trans form.

According to another embodiment, R ₁ may be an alkoxy group having 1 to 6 carbon atoms, R ₂ , R ₃ and R ₄ may be a hydroxyl group, and R ₅ and R ₆ may be hydrogen.

According to a specific embodiment, a compound represented by the following formula (2), an isomer, a solvate, or a pharmaceutically acceptable salt thereof may be provided.

According to another embodiment, an antioxidant pharmaceutical composition comprising a compound represented by the following Chemical Formula 2 or Chemical Formula 3, an isomer, a solvate, or a pharmaceutically acceptable salt thereof may be provided.

[Formula 2]

[Formula 3]

The compound represented by Formula 2 may be referred to as 8-O-4-dehydrocoumaroyl-ferulic acid.

According to another embodiment of the present disclosure,

The compound represented by any one of Formulas 1 to 3 may be obtained by separating from an extract of Aralia cordata. The poisonous bow may be an underground part of yepdurup (Tandurup). Specifically, it may be the root of yepdurup (Tandurup).

The poisonous extract may be extracted with a solvent. The solvent may be sufficient as long as it is capable of extracting the active ingredient from the poison by maintaining a liquid state during extraction. Specifically, it may be at least one selected from the group consisting of water, alcohol, chlorinated hydrocarbons, acetonitrile, tetrahydrofuran, alkyl (methyl or ethyl) acetate, and acetone, but is not limited thereto. Specifically, the solvent may be a hydrophilic solvent. The hydrophilic solvent may be water, an alcohol having 1 to 10 carbon atoms, or a mixture thereof. The alcohol may be, more specifically, an alcohol having 1 to 4 carbon atoms. The alcohol may be methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, tert-butanol, or a mixture thereof.

According to one embodiment of the present disclosure,

The solvent may be water, an alcohol solution having 1 to 4 carbon atoms, or a mixture thereof. For example, extraction may be performed with 100% water, for example, extraction may be performed with 100% methanol or ethanol. The alcohol aqueous solution is 5% (v / v), 10% (v / v), 20% (v / v), 30% (v / v), 40% (v / v), 50% (v / v) ), 60% (v/v), 70% (v/v), 80% (v/v), 90% (v/v), 95% (v/v) and 99% (v/v) It may be an aqueous alcohol solution having a concentration in a range expressed by any two numerical values selected from the group consisting of. Specifically, the alcohol concentration of the aqueous alcohol solution is about 1 to about 99% (v / v), for example, about 10 to about 99% (v / v), about 30 to about 95% (v / v), about 50 to about 90% (v/v), about 60 to about 80% (v/v), about 50 to about 80% (v/v), about 50 to about 70% (v/v), or about 60 to about 90% (v/v). The alcohol aqueous solution may be a methanol aqueous solution or an ethanol aqueous solution.

The extraction is about 1 to about 100 (volume/weight) times, for example, about 1 to about 50 (volume/weight) times, about 3 to about 20 (volume/weight) times, about 3 to about 20 (volume/weight) times, about 3 to about 50 (volume/weight) times, about 5 to about 25 (volume/weight) times, or about 4 to about 30 times. For example, about 1 to about 100 L of the extraction solvent may be added with respect to 1 kg of the dry weight of the poison activity, for example, about 3 to about 15 L may be added, for example, from about 5 to about 15 L It may be to add about 50 L, for example, about 10 to about 30 L may be added, for example, about 20 to about 30 to about 75 L may be added, for example, about 1 to about 15 L may be added.

The extraction is performed by warmed liquid extraction, pressurized liquid extraction (PLE), microwave assisted extraction (MAE), subcritical extraction (SE), or a combination thereof. can be The subcritical extraction may be subcritical water extraction (SWE). Subcritical water extraction is also referred to as superheated water extraction or pressurized hot water extraction (PHWE). The warmed liquid extraction may be reflux extraction.

The extraction may be expressed in a range of any two values selected from 1°C, 10°C, 20°C, 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, and 100°C. . Specifically, for example, from about 1 °C to about 100 °C, for example from about 10 °C to about 80 °C, from about 10 °C to about 70 °C, from about 10 °C to about 30 °C, from about 10 °C to about 50 °C, about It may be carried out at 20 °C to about 70 °C, about 20 °C to about 60 °C, about 30 °C to about 50 °C.

The extraction time may be, for example, from about 0.1 hour to about 2 months, such as from about 0.1 hour to about 10 days, such as from about 0.1 hour to about 3 days, such as from about 0.1 hour to about 1 day, such as For example from about 0.1 hour to 12 hours, such as from about 0.1 hour to about 6 hours, such as from about 0.1 hour to about 1 hour, such as from about 0.5 hour to about 2 months, such as from about 1 hour to about 1 hour months, such as about 1 hour to about 15 days, such as about 1 hour to about 10 days, such as about 1 hour to about 5 days, such as about 1 hour to about 3 days, such as about 1 hour to about 2 days, such as about 1 hour to about 1 day, such as about 3 hours to about 1 month, such as about 5 hours to about 15 days, such as about 5 hours to about 10 days, e.g. For example from about 5 hours to about 5 days, such as from about 5 hours to about 3 days, such as from about 5 hours to about 2 days, such as from about 5 hours to about 1 day, such as from about 10 hours to about 1 month, such as about 10 hours to about 15 days, such as about 10 hours to about 10 days, such as about 10 hours to about 5 days, such as about 10 hours to about 3 days, or for example For example, it may be about 10 hours to about 2 days.

The extraction may be repeated 1 to 5 times. The repetition may mean that the extraction is performed one or more times, the extract is filtered, and the remaining poisonous activity is immersed again in the extraction solvent to proceed with the extraction.

The poisonous extract may be a crude extract, a fraction, or a combination thereof. The crude extract is obtained by contacting the poisonous activity with an extraction solvent under certain conditions, and may mean that it contains many components and does not separate only specific components. The fraction may be obtained by solvent fractionation. The solvent fractionation may be to mix the crude extract with a solvent and separate substances present in the solvent. The fractionation may be repeated 1 to 5 times. The fraction is a hexane fraction, dichloromethane fraction, ethyl acetate fraction, n-butanol fraction, water fraction obtained by suspending the poisonous extract in water and sequentially fractionating it with hexane, dichloromethane, ethyl acetate and n-butanol. may be a combination of Specifically, it may be a dichloromethane fraction, an ethyl acetate fraction, an n-butanol fraction, or a combination thereof.

According to another embodiment of the present disclosure,

The fraction may be a composition subdivided by performing chromatography on the extract or fraction. Specifically, it may be, for example, chromatography according to polarity, for example, chromatography according to molecular weight, or, for example, chromatography according to a combination thereof. More specifically, it may be a fraction by liquid-liquid chromatography with different immiscible solvents, and may be a fraction by column chromatography divided by passing through a column by a gradual change in the polarity of the solvent, and may be composed of porous particles. It may be a fraction according to molecular size by passing through a column, but is not limited thereto. Alternatively, it may be another fraction obtained by gradually changing the ratio of solvents of different polarities using column chromatography with respect to the extract or fraction. Specifically, in two different solvents A and B, the ratio of A:B is about 0:100, 1:100, 1:90, 1:80, 1:60, 1:50, 1:40, 1:30, 1:20, 1:10, 1:7, 1:5, 1:3, 1:2, 1:1 and 1:0 the fraction obtained using column chromatography with a mixture causing stepwise polarity change can For example, A may be ethyl acetate and B may be n-hexane. The filler in the column chromatography may be a normal phase or reverse phase silica gel, and may be a filler having porous particles. The chromatography may be performed 1 to 5 times under different conditions. The chromatography may be MPLC, or may be HPLC. The HPLC may be semi-preparative HPLC.

According to one embodiment of the present disclosure,

A composition comprising a compound represented by any one of Formulas 1 to 3, an isomer, a solvate or a pharmaceutically acceptable salt thereof may be an antioxidant composition, an antioxidant pharmaceutical composition, an antioxidant food composition, a health functional food composition, or an antioxidant cosmetic composition have.

Without being limited to a particular theory, the composition may be an antioxidant composition that rapidly removes active oxygen.

The active oxygen is a generic term for harmful and strong oxidizing oxygen compounds generated in the process in which oxygen that enters the body through respiration is used for various energy metabolism, and attacks cells to cause loss of function or alteration. As described above, a tumor or cancer may occur in an organ in the body due to cellular alteration. The “cancer” is a malignant tumor that has rapid growth, invasive growth, and angiogenic effects, so it spreads and metastasizes to each part of the body, and may mean a malignant tumor that poses a risk to life, and can occur in any part of the body. have. Specifically, “cancer” refers to leukemia, thyroid cancer, breast cancer, biliary tract cancer, gallbladder cancer, pancreatic cancer, colon cancer, uterine cancer, esophageal cancer, stomach cancer, brain cancer, rectal cancer, lung cancer, bladder cancer, kidney cancer, ovarian cancer, prostate cancer, uterine cancer, head and neck cancer, It may be at least one selected from the group consisting of skin cancer and liver cancer, but is not limited thereto. Alternatively, active oxygen may cause abnormalities in the production and function of enzymes and hormones in the body, thereby causing biochemical cellular aging of the cardiovascular system and the nervous system.

According to one embodiment of the present disclosure,

The compound represented by any one of Formulas 1 to 3, an isomer, a solvate, or a pharmaceutically acceptable salt thereof is 0.001 wt%, 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, based on the total weight of the composition , 1.0 wt%, 3 wt%, 5 wt%, 10 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt% and 90 wt% It may be included as much as a range of any two numerical values. For example, about 0.001% to about 95%, about 0.01% to about 90%, about 0.01% to 80%, about 0.01% to 70%, about 0.01% by weight relative to the total weight of the composition % to 60%, about 0.01% to about 50%, about 0.01% to about 30%, about 0.05% to 25%, about 0.05% to 15%, about 0.05% to 5 wt%, about 0.1 wt% to about 20 wt%, about 1.0 wt% to 10 wt%, about 1.0 wt% to about 5 wt%, about 5 wt% to about 50 wt%, about 5 wt% to about 40 wt% % or about 10% to about 50% by weight of the compound represented by Formula 1 or 2, an isomer, a solvate, or a pharmaceutically acceptable salt thereof.

According to a specific embodiment of the present disclosure, the composition may be a pharmaceutical composition. A pharmaceutically acceptable carrier may be included in the composition. The pharmaceutically acceptable carrier may be at least one selected from the group consisting of a binder, a lubricant, a disintegrant, an excipient, a solubilizer, a dispersant, a stabilizer, a suspending agent, a color, and a flavoring agent for oral administration, but is limited thereto it is not In the case of injections, buffers, preservatives, analgesics, solubilizers, isotonic agents or stabilizers may be mixed and used, and in the case of topical administration, bases, excipients, lubricants or preservatives may be mixed and used.

The dosage form of the pharmaceutical composition of the present disclosure may be prepared in various ways by mixing with a pharmaceutically acceptable carrier as described above. For example, in the case of oral administration, it can be prepared in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc., and in the case of injections, it can be prepared in the form of unit dose ampoules or multiple doses. In addition, it can be formulated as a solution, suspension, tablet, capsule, sustained release formulation, and the like.

Meanwhile, examples of suitable carriers, excipients or diluents for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil may be used. In addition, fillers, anti-agglomeration agents, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like may be further included.

The route of administration of the pharmaceutical composition according to the present disclosure is, but not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal. Oral or parenteral administration is preferred. The administration may be systemically or locally.

In the present disclosure, "parenteral" includes subcutaneous, intradermal, intravenous, intramuscular, intra-articular, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques. The pharmaceutical compositions of the present disclosure may also be administered in the form of suppositories for rectal administration. The administration is 0.1 mg to 1,000 mg, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg may be administered.

The dosage of the composition may be, for example, from about 0.001 mg/kg to about 100 mg/kg on an adult basis, for example, from about 0.01 mg/kg to about 10 mg/kg, or, for example, about 0.1 mg/kg to about 1 mg/kg. The administration frequency may be administered once a day, multiple times a day, 2-3 times a week, 1-4 times a month, or 1-12 times a year.

According to the present disclosure, the pharmaceutical composition may further include a composition for preventing, improving or treating similar diseases. Specifically, an antioxidant composition may be further included, an antioxidant composition may be further included, a composition for improving liver function may be further included, and a composition for protecting the gastrointestinal tract may be further included, but is not limited thereto.

According to another embodiment of the present disclosure,

A composition comprising a compound represented by any one of Formulas 1 to 3, an isomer, a solvate, or a pharmaceutically acceptable salt thereof may be a cosmetic composition. The cosmetic composition may further include a cosmetically acceptable excipient or carrier. The carrier may be an excipient, a disintegrant, a binder, a lubricant, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant may be sodium starch glycolate, anhydrous calcium monohydrogen phosphate, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.

The cosmetic composition may be formulated in a parenteral dosage form. The parenteral dosage form may be an injection or an external preparation for skin. The external preparation for skin may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal patch, drug-containing bandage, lotion, or a combination thereof. The external preparation for skin is a component usually used in external preparations for skin such as cosmetics or pharmaceuticals, for example, an aqueous component, an oily component, a powder component, alcohol, a moisturizer, a thickener, an ultraviolet absorber, a whitening agent, a preservative, an antioxidant, a surfactant, a fragrance , coloring agents, and various skin nutrients can be appropriately blended as needed. The external preparation for skin includes metal sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belapamil, licorice extract, glablidine, and kaline. Fruit hot water extract, various herbal medicines, drugs such as tocopherol acetate, glitylic acid, tranexamic acid and derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, Sugars, such as trehalose, etc. can be mix|blended suitably.

According to another embodiment of the present disclosure,

The composition contains lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, hand cream, foundation, essence, nourishing essence, pack, soap, It may be prepared in a formulation including a cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, suspension, gel, powder, paste, mask pack or sheet or aerosol composition. The composition of such a formulation can be prepared according to a method conventional in the art. The cosmetic composition may further include preservatives, stabilizers, surfactants, solubilizers, moisturizers, emollients, UV absorbers, preservatives, bactericides, antioxidants, pH adjusters, organic and inorganic pigments, fragrances, cooling agents or limiting agents, etc. have. The blending amount of the additional ingredients such as the moisturizing agent can be easily selected by those skilled in the art within the range that does not impair the purpose and effect of the present disclosure, and the blending amount is about 0.001 to about 10 wt%, specifically, based on the total weight of the composition from about 0.01 to about 3 weight percent.

According to one embodiment of the present disclosure,

A composition comprising a compound represented by any one of Formulas 1 to 3, an isomer, a solvate, or a pharmaceutically acceptable salt thereof may be a food composition. The composition may contain various flavoring agents or natural carbohydrates as additional ingredients, as in a conventional food composition. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. The above-mentioned flavoring agents can advantageously use natural flavoring agents (taumatine), stevia extracts (eg rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).

The food composition may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the food composition can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements. have.

According to another embodiment,

The food composition includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids , a protective colloidal thickener, a pH adjuster, a stabilizer, a preservative, glycerin, alcohol, a carbonation agent used in carbonated beverages, and the like. In addition, the food composition of the present invention may further include natural fruit juice, fruit juice, and pulp for the production of fruit juice beverages and vegetable beverages.

A composition comprising a compound represented by any one of Formulas 1 to 3, an isomer, a solvate, or a pharmaceutically acceptable salt thereof is a material to be extracted from a natural product and has almost no side effects, so it can be safely used even when taken for a long period of time.

It is possible to provide an antioxidant health functional food containing the food composition. The health functional food may be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, and the like. “Health functional food” refers to food manufactured and processed using raw materials or ingredients useful for the human body in accordance with the Health Functional Food Act No. 6727, and by adjusting nutrients for the structure and function of the human body or It refers to ingestion for the purpose of obtaining useful effects for health purposes, such as physiological action. The health functional food may include normal food additives, and unless otherwise specified, whether it is suitable as a food additive or not, according to the general rules and general test method of food additives approved by the Food and Drug Administration, the standards and It is judged according to the standard. The items listed in the “Food Additives Code” include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, high pigment, and guar gum; and mixed preparations such as sodium L-glutamate preparations, noodles-added alkalis, preservatives, and tar dye preparations. For example, a health functional food in tablet form is a mixture of a composition comprising a compound represented by Formula 1 or 2, an isomer, solvate or pharmaceutically acceptable salt thereof, and a mixture of excipients, binders, disintegrants and other additives can be granulated by a conventional method, and then compression-molded by adding a lubricant or the like, or the mixture can be directly compression-molded. In addition, the health functional food in the form of tablets may contain a corrosive agent and the like as needed.

For example, among the health functional foods in capsule form, hard capsules include a compound represented by any one of Formulas 1 to 3, an isomer, a solvate, or a pharmaceutically acceptable salt thereof in a conventional hard capsule. Compositions and excipients, etc. It can be prepared by filling a mixture mixed with the additives of the above formulas 1 to 3, a composition comprising a compound represented by any one of formulas 1 to 3, an isomer, a solvate or a pharmaceutically acceptable salt thereof, and additives such as excipients It can be prepared by filling a mixture mixed with a capsule base such as gelatin. The soft capsules may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.

For example, a health functional food in the form of a ring is a composition comprising a compound represented by any one of Formulas 1 to 3, an isomer, a solvate or a pharmaceutically acceptable salt thereof, and an excipient, binder, disintegrant, etc. The mixture may be prepared by molding by a known method, and if necessary, it may be coated with sucrose or other peeling agent, or the surface may be coated with a material such as starch or talc.

For example, a health functional food in the form of granules is a mixture of a composition comprising a compound represented by any one of Formulas 1 to 3, an isomer, a solvate, or a pharmaceutically acceptable salt thereof, and an excipient, binder, disintegrant, etc. can be prepared in the form of granules by a conventionally known method, and may contain a flavoring agent, a flavoring agent, etc. as necessary.

The health functional food may be beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements.

Example 1-1: Separation of components of 8-O-4-Dehydrocoumaroyl-ferulic acid

As shown in FIG. 1, the dried poison active powder was immersed in 70% ethanol (EtOH) at room temperature and extracted twice, filtered with filter paper, and the solvent was removed using a vacuum concentrator (BuChi, 50L) to extract EtOH got Sequential solvent fractionation was performed on the poisonous extract using n-hexane, CH ₂ Cl ₂ , EtOAc, and n-BuOH. MPLC filled with reverse phase silica gel (ODS) for the ethyl acetate fraction of the poisonous extract was performed at 150 ml/min for 80 minutes with water containing acetonitrile and 0.05% trifluoroacetic acid, and 8-O-4-dehydrocoumaroyl- The ferulic acid was separated and purified.

Example 1-2: Structural identification of 8-O-4-Dehydrocoumaroyl-ferulic acid

Information on the connection relationship between protons and carbon and mass data through ^{NMR data (1} H-, ¹³ C-NMR, ¹ H- ¹ H COSY, HSQC, HMBC) analyzed using 700 MHz NMR (cryo probe) The structure was identified by confirming the molecular formula used.

8-O-4-dehydrocoumaroyl-ferulic acid White amorphous powder ¹ H-NMR (700 MHz, methanol-d ₄ ) δ 7.61 (1H, d, J = 16.1 Hz, H-7), 7.56 (2H, d, J = 9.1 Hz, H-3', 5'), 7.38 (1H, s, H-7'), 7.31 (1H, d, J = 2.1 Hz, H-2), 7.06 (1H, dd, J = 8.4, 2.1 Hz, H-6), 6.78 (1H, d, J = 8.4 Hz, H-5), 6.73 (2H, d, J = 9.1 Hz, H-2', 6'), 6.38 (1H, d, J = 16.1 Hz, H-8), 3.97 ( 3H, s, 3-OCH ₃ ); ¹³ C-NMR (175 MHz, methanol-d ₄ ) δ 170.6 (C-9), 166.6 (C-7′), 160.6 (C-4′), 150.8 (C-3), 149.4 (C-4) , 146.2 (C-7), 138.8 (C-8'), 133.5 (C-3', 5'), 130.7 (C-1), 129.0 (C-7), 125.2 (C-1'), 123.2 (C-6), 117.8 (C-8), 116.7 (C-2', 6'), 115.2 (C-5), 113.1 (C-1), 56.9 (3-OCH ₃ );
ESI-MS m/z 357 [M + H] ⁺ , 355 [M - H] ^- .

Example 2: Antioxidant activity of 8-O-4-Dehydrocoumaroyl-ferulic acid

The radical scavenging ability of ABTS[2,2'-azin0-bis(3-ethylbenzthiazoline-6-sulfonate)] is that the ABTS free radical generated by the reaction with potassium persulfate is removed by the antioxidant material of the sample. It was measured by a method using the discoloration of a characteristic color, cyan. A 7.2 mM ABTS solution was mixed with 2.6 mM potassium sulfate and then reacted in the dark for about 15 hours. After diluting this to an absorbance of 1.5 at 734 nm, take 300 μl, mix 20 μl of each solvent fraction, and react in the dark for 30 minutes to measure the absorbance at 734 nm. The difference in absorbance between the sample addition group and the control group (Ascorbic acid) is expressed as a percentage.

According to this, 8-O-4-dehydrocoumaroyl-ferulic acid exhibits a dose-dependent radical scavenging activity, and although it is somewhat inferior to ascorbic acid, a control group, significant radical scavenging activity is observed.

Claims (8)

a compound represented by the following formula (1), an isomer, a solvate, or a pharmaceutically acceptable salt thereof;
[Formula 1]

The R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are each independently hydrogen, a hydroxyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a carbonyl group (-CO-R ₇ ) , a carboxyl group (-CO-OR ₇ ), an alcohol group having 1 to 6 carbon atoms, or a substituted or unsubstituted phenylpropanoid group (C6C3),
wherein R ₇ is hydrogen, a hydroxyl group, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms. The method of claim 1,
The R ₁ , R ₂ , R ₃ , R ₄ and R ₅ are each independently hydrogen, a hydroxyl group or an alkoxy group having 1 to 6 carbon atoms, wherein R ₆ is hydrogen, a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms, or a substituted phenylpropanoid ego,
The phenylpropanoid is a cis or trans form of coumaric acid or ferulic acid, a compound, an isomer, a solvate, or a pharmaceutically acceptable salt thereof. The method of claim 1,
Wherein R ₁ is an alkoxy group having 1 to 6 carbon atoms, R ₂ , R ₃ and R ₄ are a hydroxyl group, and R ₅ and R ₆ are hydrogen. A compound, an isomer, a solvate, or a pharmaceutically acceptable salt thereof. 4. The method of claim 3,
The compound is a compound, characterized in that isolated from the poison (Aralia cordata), an isomer, a solvate or a pharmaceutically acceptable salt thereof. A pharmaceutical composition for antioxidants comprising the compound of claim 3 or 4, an isomer, a solvate, or a pharmaceutically acceptable salt thereof. A food composition for antioxidants comprising the compound of claim 3 or 4, an isomer, a solvate, or a pharmaceutically acceptable salt thereof. A health functional food composition for antioxidants comprising the compound of claim 3 or 4, an isomer, a solvate, or a pharmaceutically acceptable salt thereof. A cosmetic composition for antioxidants comprising the compound of claim 3 or 4, an isomer, a solvate, or a pharmaceutically acceptable salt thereof.

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