KR102639329B1 - A novel constituent derived from Aralia cordata and uses thereof - Google Patents

Abstract

The present disclosure relates to a new lignan compound isolated from a poisonous plant and its use, and specifically relates to a new lignan compound isolated and purified from a poisonous plant and an antioxidant composition containing the same. The composition according to the present disclosure can be usefully used as a medicine, food, and cosmetic material.

Description

A novel lignan compound derived from Aralia cordata and its uses {A novel constituent derived from Aralia cordata and its uses}

It relates to a novel lignan compound isolated from a poisonous extract and an antioxidant composition containing it as an active ingredient.

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

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

Dokhwa is the root of aralia or aralia. Aralia is a perennial herbaceous plant belonging to the Araliaceae family and is a wild or cultivated plant in Korea, China, and Japan. It is a herbal medicine that has been used to treat pain relief, edema, fever, toothache, arthritis, etc., and its young leaves and stems are It is a popular herb with a unique aroma and is a useful plant resource that is exported overseas. In particular, it is known to have antioxidant, platelet aggregation inhibitory, and antipyretic effects.

Therefore, it is necessary to isolate compounds from poisonous substances that have various effects and present them as lead or candidate substances for antioxidant medicine.

According to one embodiment of the present disclosure, it relates to a new lignan compound isolated from poisonous lignans and its use.

According to another embodiment, the object is to provide an antioxidant pharmaceutical composition, food composition, health functional food composition, or cosmetic composition containing the above compound, its isomer, solvate, or pharmaceutically acceptable salt.

According to an embodiment of the present disclosure,

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

[Formula 1]

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, or 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,

An antioxidant pharmaceutical composition, food composition, health functional food composition, or cosmetic composition containing the above compound, its isomer, solvate, or pharmaceutically acceptable salt is provided.

The compound represented by Formula 1 of the present disclosure, its isomer, solvate or pharmaceutically acceptable salt has excellent antioxidant effect by quickly removing oxidation radicals.

In addition, an antioxidant pharmaceutical composition containing the compound represented by Formula 1, an isomer, solvate or pharmaceutically acceptable salt thereof, an antioxidant health functional food or an antioxidant cosmetic composition containing the same can be provided.

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

The present disclosure can all be achieved by the following description. The following description should be understood as describing embodiments of the present disclosure, and is not necessarily limited thereto. In addition, it should be understood that the attached drawings are for aiding understanding and that the present disclosure is not limited thereto.

Embodiments of the present disclosure may be subject to various changes and may be implemented in various forms. Accordingly, it should be understood to include all changes, equivalents, and substitutes within the scope where the same spirit and technical features of the present disclosure are acknowledged.

Unless otherwise specified, all numbers used in this disclosure are to be understood in all instances as being modified by the term “about.” The modifier “about” is intended to have a commonly recognized approximate meaning, which can be more accurately interpreted as meaning within a certain percentage of the modified value, and more specifically, ±20%, ±10%, ± It may mean 5%, ±2% or ±1% or less.

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

“Alkyl group” may refer to a monovalent group derived from a straight-chain or branched-chain saturated hydrocarbon, and may be substituted or unsubstituted. Examples of such alkyl groups having 1 to 6 carbon atoms include methyl (Me, -CH ₃ ), ethyl (Et, -CH ₂ CH ₃ ), and 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 this is only an example, and the alkyl group of the present disclosure is not limited to having 1 to 6 carbon atoms.

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

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

According to another embodiment, a pharmaceutical composition for antioxidant containing a compound represented by the following formula (1), an isomer, solvate, or pharmaceutically acceptable salt thereof may be provided.

[Formula 1]

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, or 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, and R ₆ may be hydrogen, a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms, or a substituted phenylpropa It could be a noid.

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

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

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

According to another embodiment, a pharmaceutical composition for antioxidants containing a compound represented by Formula 2 or Formula 3 below, an isomer, solvate, or 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,

Compounds represented by any one of Formulas 1 to 3 may be obtained by separating them from Aralia cordata extract. The solitary arch may be the underground part of the aralia (ground aralia). Specifically, it may be the root of the ground aralia.

The poisonous extract may be extracted with a solvent. The solvent that can maintain a liquid state during extraction and extract the active ingredient from the poison will be sufficient. 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. More specifically, the alcohol may be 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 mixtures thereof.

According to one embodiment of the present disclosure,

The solvent may be water, an alcohol aqueous solution having 1 to 4 carbon atoms, or a mixture thereof. For example, it can be extracted with 100% water, and for example, it can be extracted 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 alcohol aqueous solution having a concentration in a range expressed by any two numbers selected from the group consisting of. Specifically, the alcohol concentration of the alcohol aqueous 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 It may be from about 90% (v/v). The alcohol aqueous solution may be an aqueous methanol solution or an aqueous ethanol solution.

The extraction is performed by using the extraction solvent at 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, It may include adding 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 per 1 kg of dry weight of the poison, for example, about 3 to about 15 L may be added, for example, about 5 to about 15 L. It may be adding about 50 L, for example, it may be adding about 10 to about 30 L, for example, it may be adding about 20 to about 30 to about 75 L, for example, it may be adding about 1 to about 75 L. It may be adding 15 L.

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

The extraction may be expressed as 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, about 1°C to about 100°C, for example, about 10°C to about 80°C, about 10°C to about 70°C, about 10°C to about 30°C, about 10°C to about 50°C, about It may be performed at 20°C to about 70°C, about 20°C to about 60°C, or about 30°C to about 50°C.

The extraction time may be, for example, from about 0.1 hour to about 2 months, for example from about 0.1 hour to about 10 days, for example from about 0.1 hour to about 3 days, for example from about 0.1 hour to about 1 day, for example For example from about 0.1 hour to about 12 hours, for example from about 0.1 hour to about 6 hours, for example from about 0.1 hour to about 1 hour, for example from about 0.5 hour to about 2 months, for example from about 1 hour to about 1 hour. months, for example from about 1 hour to about 15 days, for example from about 1 hour to about 10 days, for example from about 1 hour to about 5 days, for example from about 1 hour to about 3 days, for example about 1 hour to about 2 days, for example from about 1 hour to about 1 day, for example from about 3 hours to about 1 month, for example from about 5 hours to about 15 days, for example from about 5 hours to about 10 days, for example For example from about 5 hours to about 5 days, for example from about 5 hours to about 3 days, for example from about 5 hours to about 2 days, for example from about 5 hours to about 1 day, for example from about 10 hours to about 1 day. 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 e.g. 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 carried out one or more times, the extract is filtered, and the remaining poison is immersed in the extraction solvent again 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 poison with an extraction solvent under certain conditions, and may mean that it contains many components and only specific components are not separated. The fraction may be obtained by solvent fractionation. The solvent fractionation may be mixing the crude extract with a solvent and separating 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, or these obtained by suspending the inert extract in water and sequentially fractionating it with hexane, dichloromethane, ethyl acetate, and n-butanol. It may be a combination of Specifically, it may be a dichloromethane fraction, ethyl acetate fraction, n-butanol fraction, or a combination thereof.

According to another embodiment of the present disclosure,

The fraction may be a composition refined by performing chromatography on an extract or fraction. Specifically, for example, it may be chromatography according to polarity, for example, it may be chromatography according to molecular weight, or for example, it may be chromatography according to a combination thereof. More specifically, it may be a fraction by liquid-liquid chromatography using different immiscible solvents, it may be a fraction by column chromatography where it is divided by passing through a column due to a gradual change in the polarity of the solvent, and it may be a fraction made of porous particles. It may be a fraction according to molecular size after passing through a column, but is not limited to this. Alternatively, it may be another fraction obtained by gradually varying the ratio of solvents of different polarities to the extract or fraction using column chromatography. 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, Fractions obtained using column chromatography with a mixture that changes polarity stepwise to 1:20, 1:10, 1:7, 1:5, 1:3, 1:2, 1:1 and 1:0. You can. For example, A may be ethyl acetate and B may be n-hexane. The filler for the column chromatography may be normal phase or reverse phase silica gel, and may be a filler with porous particles. The chromatography can 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 containing a compound represented by any of Formulas 1 to 3, an isomer, solvate, or 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. there is.

Although not limited to a specific theory, the composition may be an antioxidant composition that quickly removes active oxygen radicals.

The term active oxygen is a general term for harmful and highly oxidizing oxygen compounds that occur when oxygen entering the body through breathing is used for various energy metabolism. It attacks cells and causes them to lose function or deteriorate. As described above, tumors or cancer may occur in internal organs due to cell degeneration. The term “cancer” refers to a malignant tumor that has rapid growth, invasive growth, and neovascularization effects, and can spread and metastasize to all parts of the body, causing a risk to life. It can occur in any part of the human body. there is. Specifically, “cancer” refers to leukemia, thyroid cancer, breast cancer, biliary tract cancer, gallbladder cancer, pancreatic cancer, colon cancer, uterine cancer, esophagus 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, causing biochemical cell aging of the cardiovascular and nervous systems, etc.

According to one embodiment of the present disclosure,

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

According to certain embodiments of the present disclosure, the composition may be a pharmaceutical composition. The composition may include a pharmaceutically acceptable carrier. For oral administration, the pharmaceutically acceptable carrier may be at least one selected from the group consisting of binders, lubricants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, colorants, and flavoring agents, but is limited thereto. That is not the case. In the case of injections, buffers, preservatives, analgesics, solubilizers, isotonic agents, or stabilizers can be mixed, and in the case of topical administration, bases, excipients, lubricants, or preservatives can be mixed.

The dosage form of the pharmaceutical composition of the present disclosure can be prepared in various ways by mixing it with a pharmaceutically acceptable carrier as described above. For example, for oral administration, it can be manufactured in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc., and for injections, it can be manufactured in the form of unit dosage ampoules or multiple dosage forms. It can also be formulated as a solution, suspension, tablet, capsule, sustained-release preparation, etc.

Meanwhile, examples of carriers, excipients or diluents suitable 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-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives, etc. may be additionally included.

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

In this disclosure, “parenteral” includes subcutaneous, intradermal, intravenous, intramuscular, intra-articular, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques. Pharmaceutical compositions of the present disclosure can 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 mg per single administration of the poisonous extract or its fraction. 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, about 0.001 mg/kg to about 100 mg/kg, for example, about 0.01 mg/kg to about 10 mg/kg, or for example, about It may be from 0.1 mg/kg to about 1 mg/kg. The frequency of administration may be once a day, multiple times a day, 2 to 3 times a week, 1 to 4 times a month, or 1 to 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 containing a compound represented by any one of Formulas 1 to 3, an isomer, solvate, or pharmaceutically acceptable salt thereof may be a cosmetic composition. The cosmetic composition may further include cosmetically acceptable excipients or carriers. The carrier may be an excipient, disintegrant, binder, 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, calcium monohydrogen phosphate anhydride, 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 as a parenteral dosage form. The parenteral dosage form may be an injection or a topical preparation for skin. External skin preparations may be creams, gels, ointments, skin emulsifiers, skin suspensions, transdermal patches, drug-containing bandages, lotions, or combinations thereof. The skin external preparations include ingredients commonly used in external skin preparations such as cosmetics and medicines, such as aqueous ingredients, oil-based ingredients, powder ingredients, alcohols, moisturizers, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, and fragrances. , colorants, and various skin nutrients can be appropriately mixed as needed. The skin external preparations include metal sequestrants such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belafamil, licorice extract, glablidin, and calin. Hot water extracts of fruit, various herbal medicines, drugs such as tocopherol acetate, glytylitinic acid, tranexamic acid and its derivatives or salts, vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, glucose, fructose, Sugars such as trehalose can also be appropriately mixed.

According to another embodiment of the present disclosure,

The composition includes lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, foundation, essence, nutritional essence, pack, soap, It can be manufactured into a formulation containing cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, suspension, gel, powder, paste, mask pack or sheet, or aerosol composition. Compositions of this dosage form can be prepared according to methods conventional in the art. The cosmetic composition may further include preservatives, stabilizers, surfactants, solubilizers, moisturizers, emollients, ultraviolet absorbers, preservatives, disinfectants, antioxidants, pH adjusters, organic and inorganic pigments, fragrances, cooling agents or antiperspirants. there is. The mixing amount of additional ingredients such as the moisturizer can be easily selected by a person skilled in the art within a range that does not impair the purpose and effect of the present disclosure, and the mixing amount is about 0.001 to about 10% by weight, specifically, based on the total weight of the composition. It may be about 0.01 to about 3 weight percent.

According to one embodiment of the present disclosure,

A composition containing a compound represented by any one of Formulas 1 to 3, an isomer, solvate, or pharmaceutically acceptable salt thereof may be a food composition. The composition may contain various flavoring agents or natural carbohydrates as additional ingredients, like ordinary food compositions. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The above-described flavoring agents include natural flavoring agents (thaumatin), stevia extracts (e.g. rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).

The food composition can be formulated in the same way 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, gum, candy, ice cream, alcoholic beverages, vitamin complexes, and health supplements. there is.

According to another embodiment,

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

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

Antioxidant health functional food containing the above food composition can be provided. The health functional food can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. “Health functional food” refers to food manufactured and processed using raw materials or ingredients with functional properties useful to the human body in accordance with Act No. 6727 on Health Functional Food, and that adjusts nutrients for the structure and function of the human body. It means ingestion for the purpose of obtaining useful effects for health purposes such as physiological effects. The above health functional food may contain common food additives, and its suitability as a food additive is determined by the specifications and standards for the relevant item in accordance with the general provisions of the Food Additive Code and General Test Methods approved by the Food and Drug Administration, unless otherwise specified. Judgment is made according to standards. Items listed in the “Food Additive Code” include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as dark pigment, licorice extract, crystalline cellulose, high-quality pigment, and guar gum; Examples include mixed preparations such as sodium L-glutamate preparations, noodle additive alkaline preparations, preservative preparations, and tar coloring preparations. For example, a health functional food in tablet form is a mixture of a composition containing a compound represented by Formula 1 or 2, an isomer, solvate, or pharmaceutically acceptable salt thereof, and excipients, binders, disintegrants, and other additives. It can be granulated by a conventional method and then compression molded by adding a lubricant, etc., or the mixture can be directly compression molded. In addition, the health functional food in the form of tablets may contain flavoring agents, etc., if necessary.

For example, a hard capsule among capsule-type health functional foods is a composition containing a compound represented by any of the above formulas 1 to 3, an isomer, solvate, or pharmaceutically acceptable salt thereof in a regular hard capsule, and excipients, etc. It can be manufactured by filling a mixture mixed with additives, and the soft capsule is a composition containing a compound represented by any of the formulas 1 to 3, an isomer, solvate or pharmaceutically acceptable salt thereof, and additives such as excipients. It can be manufactured by filling the mixture with a capsule base such as gelatin. The soft capsule may contain plasticizers such as glycerin or sorbitol, colorants, preservatives, etc., if necessary.

For example, a health functional food in the form of a ring is a mixture of a composition containing a compound represented by any one of Formulas 1 to 3, an isomer, solvate or pharmaceutically acceptable salt thereof, and excipients, binders, disintegrants, etc. The mixture can be prepared by molding by a known method, and if necessary, it can be coated with white sugar or another coating agent, or the surface can be coated with a substance such as starch or talc.

For example, a granular health functional food is a mixture of a composition containing a compound represented by any one of the above formulas 1 to 3, an isomer, solvate or pharmaceutically acceptable salt thereof, and excipients, binders, disintegrants, etc. Can be manufactured into granules by a known method, and may contain flavoring agents, flavoring agents, etc., if necessary.

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

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

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

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

Information and mass data on the connection between protons and carbon through NMR data ( ¹ H-, ¹³ C-NMR, ¹ H- ¹ H COZY, HSQC, HMBC) analyzed using a 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

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

According to this, 8-O-4-dehydrocoumaroyl-ferulic acid shows radical scavenging ability in a dose-dependent manner, and although it is slightly lower than the control ascorbic acid, significant radical scavenging ability is observed.

Claims (8)

delete delete delete delete delete An antioxidant food composition comprising a compound represented by the following formula (2), a solvate or a pharmaceutically acceptable salt thereof;
[Formula 2]
. An antioxidant health functional food composition containing a compound represented by the following formula (2), a solvate or a pharmaceutically acceptable salt thereof;
[Formula 2]
. An antioxidant cosmetic composition comprising a compound represented by the following formula (2), a solvate or a pharmaceutically acceptable salt thereof;
[Formula 2]
.