KR20230035824A - Composition for preventing, treating or ameliorating side effect of anticancer agent comprising the Extract or the isolated compounds of Polygala tenuifolia - Google Patents

Abstract

The present invention relates to a composition for preventing, treating, or alleviating anticancer drug side effects, containing a Polygala tenuifolia extract, a fraction thereof, or a compound isolated therefrom as an active component. Since the Polygala tenuifolia extract, the fraction thereof, or the compound isolated therefrom according to the present invention reduces the side effects of anticancer drugs by inhibiting the activity of beta-glucuronidase, so that it is possible to be usefully used as the composition for preventing or alleviating the side effects of anticancer drugs.

Description

Composition for preventing, treating or ameliorating side effect of anticancer agent comprising the Extract or the isolated compounds of Polygala tenuifolia}

The present invention relates to a composition for preventing, treating, or improving anticancer drug side effects, comprising a Jiji extract, a fraction thereof, or a compound isolated therefrom as an active ingredient.

Anticancer agents are chemotherapeutic agents used to inhibit the proliferation of cancer cells. It also includes a broad meaning as a treatment used before and after surgery to increase the success of surgery to suppress micrometastasis of cancer, to prevent recurrence, to prolong the survival period of terminally ill patients, or to alleviate symptoms.

When cancer is discovered, in the case of advanced cancer, chemotherapy is performed to treat cancer through anticancer drugs, and anticancer drugs are considered essential means for cancer treatment. However, anorexia, nausea, and vomiting may occur in the middle or several days after administration of anticancer drugs, and hypersensitivity reactions (skin rash, angioedema, dyspnea) may occur immediately after administration of anticancer drugs and within several hours. In addition, stomatitis, diarrhea, and neutropenic fever may occur after administration of anticancer drugs.

Irinotecan, one of the most commonly used anticancer drugs, is well known as a treatment for gastric cancer, colorectal cancer, small cell lung cancer, cervical cancer, rectal cancer, colon cancer, and ovarian cancer. It is a topoisomerase inhibitor that kills Even in the case of such widely used irinotecan, drug side effects such as diarrhea appear after taking it.

Therefore, efforts are being made to minimize these side effects, and as one part of these efforts, studies to reduce the side effects of cancer using natural products are actively conducted.

On the other hand, Wonji ( Polygala tenuifolia ) is a plant of the dicotyledonous tree Aphidaceae, and grows in low mountain areas in the north of the central part of Korea. It has excellent expectorant and mental stabilizing effects, and is known to be effective in improving forgetfulness, heart palpitations, insomnia, and cognitive disorders.

However, studies on the reduction effect of anticancer drug side effects of base paper are still incomplete.

Under this background, the present inventors have made diligent efforts to develop natural materials useful for reducing the side effects of anticancer drugs. confirmed to complete the present invention.

Republic of Korea Patent Publication No. 10-2019-0096824

The present invention aims to solve the above problems and other problems related thereto.

An exemplary object of the present invention is to provide a pharmaceutical composition for preventing or treating side effects of anticancer drugs, comprising Polygala tenuifolia extract or a fraction thereof as an active ingredient.

Another illustrative object of the present invention is to provide a pharmaceutical composition for preventing or treating side effects of anticancer drugs, comprising a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient.

Another exemplary object of the present invention is to provide an anticancer adjuvant comprising Polygala tenuifolia extract or a fraction thereof as an active ingredient.

Another exemplary object of the present invention is to provide an anticancer adjuvant comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

Another exemplary object of the present invention is to provide a food composition for preventing or improving the side effects of anticancer drugs containing Polygala tenuifolia extract or a fraction thereof as an active ingredient.

Another exemplary object of the present invention is to provide a food composition for preventing or improving the side effects of anticancer drugs, including the compound represented by Formula 1 as an active ingredient.

Another exemplary object of the present invention is to provide a food additive composition for preventing or improving anti-cancer drug side effects comprising Polygala tenuifolia extract or a fraction thereof as an active ingredient.

Another exemplary object of the present invention is to provide a food additive composition for preventing or improving anticancer drug side effects, including the compound represented by Formula 1 as an active ingredient.

Another exemplary object of the present invention is to provide a health functional food for preventing or improving anti-cancer drug side effects comprising Polygala tenuifolia extract or a fraction thereof as an active ingredient.

Another exemplary object of the present invention is to provide a health functional food for preventing or improving side effects of anticancer drugs, including the compound represented by Formula 1 as an active ingredient.

Another exemplary object of the present invention is to provide a feed composition for preventing or improving anti-cancer drug side effects comprising Polygala tenuifolia extract or a fraction thereof as an active ingredient.

Another exemplary object of the present invention is to provide a feed composition for preventing or improving anticancer drug side effects, comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

The technical problem to be achieved according to the technical idea of the invention disclosed in this specification is not limited to the problem to solve the problems mentioned above, and another problem not mentioned can be clearly understood by those skilled in the art from the following description. There will be.

A detailed description of this is as follows. Meanwhile, each description and embodiment disclosed in this application may also be applied to each other description and embodiment. That is, all combinations of various elements disclosed in this application fall within the scope of this application. In addition, the scope of the present application is not to be construed as being limited by the specific descriptions described below.

As one aspect for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating anticancer drug side effects, comprising Polygala tenuifolia extract or a fraction thereof as an active ingredient.

The term "Reservoir" of the present invention is a plant belonging to the dicotyledonous plant Aphidaceae, and is a herbal medicine that has been used for hundreds of years to improve memory, emotional stability, and sleep and cognitive disorders.

The term "anti-cancer drug side effects" of the present invention refers to negative side effects other than treatment that may occur due to the administration of anti-cancer drugs, and refers to phenomena including anorexia, vomiting, dyspnea, hair loss or diarrhea. In addition, hematopoietic toxicity, anemia, and neutropenia induced by anticancer agents are included. In the present invention, the side effect may be diarrhea.

In the present invention, cancer is lung cancer, breast cancer, liver cancer, stomach cancer, colon cancer, colon cancer, rectal cancer, skin cancer, bladder cancer, prostate cancer, ovarian cancer, cervical cancer, small cell lung cancer, thyroid cancer, kidney cancer, fibrosarcoma, melanoma, or It may be blood cancer, but is not limited thereto.

The term "anti-cancer agent" of the present invention refers to all chemotherapeutic agents used to inhibit the proliferation of cancer cells.

In the present invention, the anticancer agent may be an antitumor antibiotic, a topoisomerase inhibitor, or a taxane-based drug.

In the present invention, the antitumor antibiotic is actinomycin D, bleomycin sulfate, daunomycin, daunorubicin, doxorubicin, epirubicin ( It is preferably at least one selected from the group consisting of epirubicin, idarubicin, mitomycin, mitomycin-C, and mitramycin, but is not limited thereto.

In the present invention, the topoisomerase inhibitor is irinotecan, camptothecin, novobiocin, epirubicin, dactinomycin, amsacrine ), teniposide, and etoposide.

The irinotecan is one of the most commonly used anticancer drugs for the treatment of gastric cancer, colorectal cancer, small cell lung cancer, cervical cancer, rectal cancer, colon cancer and ovarian cancer, and more than 40% of patients taking irinotecan suffer side effects such as diarrhea. It is known.

In the present invention, the extract or a fraction thereof beta-glucuronidase ( β-glucuronidase ) can be inhibited.

Beta-gluconronidase is a glycolytic enzyme found in oil tissues, body fluids, microorganisms, plants, and strata. 45% of the base sequence is similar, and the two monomers including 597 amino residues form an asymmetric structure.

Irinotecan, an anticancer drug, is hydrolyzed by human carboxylesterases and converted into active 7-ethyl-10hydroxycamptothecin (SN-38). SN-38 has an antitumor effect by inhibiting human topoisomerase I, while it is biosynthesized into SN38-glucuronide by liver or tissue UDP-glucuronosyl transferases. . Subsequently, SN38-glucuronide released into the intestine is hydrolyzed back to SN38 by the bacterium β-glucuronidase, injuring intestinal epithelial cells and inducing diarrhea. Therefore, by inhibiting beta-gluconronidases, the hydrolysis of the metabolite to SN38 can be prevented, and diarrhea induction by irinotecan can be alleviated.

Specifically, in the experimental example of the present invention, it was confirmed that the compound isolated from the extract of the extract and the fraction of the extract of the extract inhibits the activity of beta-glucuronidase, and based on this, the extract of the extract of the extract of the present invention, the extract of the extract of the present invention, the fraction or the fraction isolated therefrom It was confirmed that the compound can be usefully used to relieve diarrhea caused by taking irinotecan, an anticancer drug, due to the inhibition of the activity of beta-gluconronidases.

The term "extract" of the present invention refers to an extract obtained by the extraction treatment of the stock paper, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, a crude or purified product of the extract, or a mixture thereof, etc. and extracts of all formulations that can be formed using the extract solution.

In the present invention, the extraction is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method include hot water extraction, cold extraction, solvent extraction, steam distillation, dissolution, compression, ultrasonic extraction, filtration, reflux extraction, and the like, which are performed alone or in combination of two or more methods. can be performed by

The extract of the present invention is obtained by extracting base paper using an appropriate solvent, and may include, for example, a crude extract, a polar solvent-soluble extract, or a non-polar solvent-soluble extract. The type of extraction solvent used to prepare the extract is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent include water; alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropanol, butanol, propyl alcohol, and butyl alcohol; polyhydric alcohols such as glycerin, butylene glycol, and propylene glycol; hydrocarbon-based solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, and dichloromethane; Or a mixture thereof may be used, and for example, it may be a solvent selected from the group consisting of water, lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.

In the present invention, the extract may be an extract of the whole plant, leaf, stem, or root of the branch, and may be, for example, an extract of the root of the branch.

The term "prevention" of the present invention refers to any activity that inhibits or delays the side effects of anticancer drugs through administration of the pharmaceutical composition of the present invention, and the term "treatment" of the present invention refers to anticancer drugs caused by administering the pharmaceutical composition of the present invention. Any action that ameliorates, alleviates, or changes beneficially a side effect. The term "improvement" of the present invention refers to all activities in which side effects of anticancer drugs are improved by administration of the composition.

In the present invention, the term "fraction" refers to a result obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.

In the present invention, the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art. It may be a solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed by passing an ultrafiltration membrane having a certain molecular weight cut-off value, a chromatographic fractionation method, and combinations thereof. In addition, in the present invention, the type of solvent used to obtain the fraction is not particularly limited, and any solvent known in the art may be used. Examples of the fractionation solvent may include nucleic acid, dichloromethane, ethyl acetate, butanol, water, an organic solvent, or a mixed solvent thereof.

In the present invention, the fractions may be obtained by a solvent fractionation method in which an oil extract is treated with a solvent, and the fractions obtained by the solvent fractionation method may be further fractionated by a chromatographic fractionation method. For example, after fractionating the stock extract into dichloromethane, ethyl acetate, and an aqueous layer, the fraction may be obtained again by performing column chromatography on the water fraction.

As another aspect of the present invention, the present invention provides a pharmaceutical composition for preventing or treating side effects of anticancer drugs, comprising a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

In the present invention, the compound may be synthetic or derived from a plant, for example, it may be derived from a stock, and for example, it may be obtained by performing chromatography from a fraction of a stock extract, for example 3′-O-(O-methylferuloyl)sucrose, sibiricose A5, 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose, tenuifoliside A, 6-O-(O-methyl-p-benzoyl)- It may be 3'-O-(O-methylsinapoyl)sucrose, arillanin A, 6,3'-di-O-sinapoylsucrose, polygalasaponin XXXII, micranthoside A, onjisaponin B, polygalasaponin XXVIII or platycodin D, specifically represented by Formula 1 below. It may be 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose.

[Formula 1]

In the present invention, the pharmaceutically acceptable salt includes an acid addition salt formed by a pharmaceutically acceptable free acid. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc., aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. Non-toxic organic acids such as dioate, aromatic acids, aliphatic and aromatic sulfonic acids, etc., organic acids such as trifluoroacetic acid, acetate, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid, etc. get from Such pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulphate, sulphite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, i. Odide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, sube Late, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate , methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybuty lates, glycolates, maleates, tartrates, methanesulfonates, propanesulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates, mandelates, and the like.

The acid addition salt according to the present invention can be prepared by a conventional method, and a pharmaceutically acceptable metal salt can be prepared using a base.

In the present invention, 4-O-benzoyl-3'-O- (O-methylsinapoyl) sucrose of Formula 1 (4-O-benzoyl-3'-O- (O-methylsinapoyl) sucrose) -Can act as a non-competitive inhibitor of glucuronidases. An uncompetitive inhibitor is a substance that inhibits the activity of an enzyme by binding to a complex between a substrate and an enzyme, and the inhibitory effect is not offset or reduced even when the concentration of the substrate is high.

Specifically, in the experimental example of the present invention, it was confirmed that 4-O-benzoyl-3'-O-(O-methylsinapoyl)sucrose acts as a non-competitive substrate inhibitor on beta-gluconronidase.

In the present invention, the compound can inhibit beta-glucuronidase ( β-glucuronidase ).

The term "pharmaceutical composition" of the present invention means prepared for the purpose of preventing or treating a disease, and may be formulated and used in various forms according to conventional methods, respectively.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent according to conventional methods. Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or dosage form, and specific reference may be made to the pharmacopoeia of each country including the 'Korean Pharmacopoeia'. Carriers, excipients and diluents that may be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition, carriers, excipients and diluents that may be included in the composition of the present invention may be non-natural carriers, but are not limited thereto.

The pharmaceutical composition of the present invention may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories or sterile injection solutions according to conventional methods. . Specifically, when formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. to the compound. It can be prepared by mixing. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, internal solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. can Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, Witepsol, Macrogol, Tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used. The specific formulation of the pharmaceutical composition is known in the art, and reference may be made to, for example, Remington's Pharmaceutical Sciences (19th ed., 1995). These documents are considered as part of this specification.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The pharmacologically effective amount means an amount that is sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects. It may be determined according to the activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, factors including drugs used in combination or concurrently, and other factors well known in the medical field. The dosage and frequency do not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention may be administered to mammals such as mice, dogs, cats, cows, horses, pigs, and humans through various routes, and may be preferably human. Any mode of administration may be expected, and may be administered by, for example, oral, intravenous, intramuscular or subcutaneous injection, but is not limited thereto.

The pharmaceutical composition of the present invention may have preventive or therapeutic effects on side effects of anticancer drugs.

The term "comprising as an active ingredient" of the present invention means that the pharmaceutical composition includes an effective amount capable of exhibiting a preventive or therapeutic effect on the side effects of anticancer drugs.

As another aspect of the present invention, the present invention provides an anticancer adjuvant comprising an extract or a fraction thereof as an active ingredient.

As another aspect of the present invention, the present invention provides an anticancer adjuvant comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the anticancer adjuvant suppresses diarrhea, hematopoietic toxicity, anemia, neutropenia, and the like caused by administration of anticancer drugs.

As another aspect of the present invention, the present invention provides a food composition for preventing or ameliorating the side effects of anti-cancer drugs comprising an extract or a fraction thereof as an active ingredient.

The terms "extract", "fraction", "compound", "prevention" or "improvement" of the present invention are as described above.

The food composition of the present invention can be prepared in various types of formulations, and unlike general drugs, there is an advantage in that there is no side effect that may occur when taking a drug for a long time using food as a raw material. The food composition of the present invention can be prepared in any form, specifically, health functional food preparations such as tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, It may be one or more formulations selected from the group consisting of beverages, gums and candies, but is not particularly limited thereto.

In addition, the food composition of the present invention may include food additives in addition to the active ingredient. Food additives can generally be understood as substances that are added to, mixed with, or infiltrated into food in manufacturing, processing, or preserving food, and their safety must be guaranteed because they are consumed daily and for a long period of time together with food. The food additives are classified into sweeteners, flavors, preservatives, emulsifiers, acidulants, thickeners, etc. in terms of function, and are not particularly limited as long as the food composition of the present invention meets the purpose to be achieved. In addition, the food composition of the present invention may include physiologically active substances or minerals that are known in the art for the purpose of functionality and nutritional supplementation and whose stability is guaranteed as food additives in addition to the above food additives. The physiologically active substance or mineral is not particularly limited as long as it meets the purpose to be achieved by the food composition of the present invention.

The food composition of the present invention may contain the above-mentioned food additives in an effective amount to achieve the purpose of addition according to the type of product, and in relation to other food additives that may be included in the food composition of the present invention, the Food Code of each country or the Food Additives Codex.

As another aspect of the present invention, the present invention provides a food composition for preventing or improving anticancer drug side effects, comprising the compound represented by Formula 1 as an active ingredient.

As another aspect of the present invention, the present invention provides a food additive composition for preventing or improving the side effects of anti-cancer drugs, comprising an extract or a fraction thereof as an active ingredient.

The terms "extract", "fraction", "compound", "prevention" or "improvement" of the present invention are as described above.

In the present invention, the term "food additive" is used in manufacturing, processing, or preserving food by adding, mixing, infiltrating, or other methods to food for the purpose of improving preservation, quality improvement, nutrition enhancement, flavor and appearance. material that can be The "food additives" may be added with the active ingredient of the present invention as it is or used together with other "food" or "food" ingredients, and the mixing amount of the active ingredient may be appropriately determined by a person skilled in the art according to the purpose of use.

According to the Food Additive Code under each country's laws governing the manufacture and distribution of food ('Food Sanitation Act' in Korea), safety-guaranteed food additives are limitedly regulated in terms of ingredients or functions. In the Korean Food Additives Codex (Ministry of Food and Drug Safety notification 'Standards and Specifications for Food Additives'), food additives are classified into chemical synthetic products, natural additives, and mixed formulations in terms of ingredients, and these food additives are classified as sweeteners and flavors in terms of function It is divided into additives, preservatives, emulsifiers, acidulants, and thickeners.

The sweetener is used to impart an appropriate sweetness to food, and may be natural or synthetic. Preferably, a natural sweetener is used, and examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.

The flavoring agent may be used to improve taste or aroma, and both natural and synthetic flavors may be used. Preferably, it is the case of using a natural one. In case of using natural ones, in addition to flavor, the purpose of enhancing nutrition can also be combined. As a natural flavoring agent, it may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, etc., or obtained from green tea leaves, roundworms, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, and the like. In addition, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, ginkgo, etc. can be used. Natural flavors can be liquid concentrates or solid extracts. In some cases, synthetic flavors may be used, and as synthetic flavors, esters, alcohols, aldehydes, terpenes, and the like may be used.

As the preservative, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc. may be used, and as the emulsifier, acacia gum, carboxymethylcellulose, xanthan gum, Pectin and the like may be used, and acidulant, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, and the like may be used as an acidulant. Acidulants may be added to the food composition to have an appropriate acidity for the purpose of inhibiting the growth of microorganisms in addition to improving taste.

As the thickening agent, a suspending agent, a sedimentation agent, a gel forming agent, a swelling agent, and the like may be used.

The food additive composition comprising the extract or a fraction thereof of the present invention can achieve the effect of preventing or improving the side effects of anticancer drugs in addition to the added food ingredients.

As another aspect of the present invention, the present invention provides a food additive composition for preventing or improving the side effects of anticancer drugs, comprising the compound represented by Formula 1 as an active ingredient.

As another aspect of the present invention, the present invention provides a health functional food for preventing or improving the side effects of anticancer drugs, comprising the extract or a fraction thereof as an active ingredient.

The terms "extract", "fraction", "compound", "prevention" or "improvement" of the present invention are as described above.

In the present invention, the term "health functional food" refers to food manufactured and processed using raw materials or ingredients having useful functionality for the human body. The above "functionality" means obtaining useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions. The health functional food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components commonly added in the art during manufacture.

In addition, the formulation of the health functional food may be manufactured without limitation as long as it is recognized as a health functional food, and non-limiting examples of the formulation include tablets, capsules, pills, granules, liquid, powder, flake, paste, syrup, It may be one or more formulations selected from the group consisting of health functional food preparations such as gels, jellies, and bars, beverages, gums, and candies, but is not particularly limited thereto.

As another aspect of the present invention, the present invention provides a health functional food for preventing or improving the side effects of anticancer drugs, comprising the compound represented by Formula 1 as an active ingredient.

As another aspect of the present invention, the present invention provides a feed composition for preventing or improving the side effects of anti-cancer drugs comprising the extract or a fraction thereof as an active ingredient.

The terms "extract", "fraction", "compound", "prevention" or "improvement" of the present invention are as described above.

As another aspect of the present invention, the present invention provides a feed composition for preventing or improving anticancer drug side effects, comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

The feed composition may include a feed additive. The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act.

In the present invention, the term "feed" may mean any natural or artificial diet, meal, etc., or components of the meal, especially for or suitable for eating, ingesting and digesting by animals.

The type of feed is not particularly limited, and feeds commonly used in the art may be used. Non-limiting examples of the feed include vegetable feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal or grain by-products; Animal feed such as proteins, inorganic materials, oils, mineral oils, oils, single cell proteins, zooplankton, or food may be mentioned. These may be used alone or in combination of two or more.

Since the extract, a fraction thereof, or a compound isolated therefrom according to the present invention reduces the side effects of anticancer drugs by inhibiting the activity of beta-glucuronidase, it can be usefully used as a composition for preventing or improving the side effects of anticancer drugs.

1 is a result showing the beta-gluconronidase inhibitory activity of the compound isolated from the fraction of the extract of the extract.
2 is a result showing beta-gluconronidase inhibitory activity for each concentration of the compound of Formula 1.
Figure 3 shows the results of enzyme kinetics of the compound of Formula 1.
Figure 4 shows the inhibition constant value ( k _i ) of the compound of Formula 1.

Hereinafter, the configuration and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

Example 1: Preparation of genotype root extracts, fractions and compounds

1-1. experimental material

ESI-MS spectra were measured with Shimadzu LCMS-8040 (Kyoto, Japan). NMR experiments were performed with ECA400/600 (JEOL, Tokyo, Japan). TLC analysis was performed on Kieselgel 60 F254 and PR-18 F254s plates (Merck, USA). The sample was immersed in 10% (v/v) H2SO4 (Aldrich, USA) solvent and dried with 300°C dry air for 30 seconds. Silica gel (Merck 60A, 70-230 or 230-400 mesh ASTM), Sephadex LH-20 (GE healthcare), reversed phase silica gel (YMC Co., ODS-A 12 nm S-150, S-75 μm) Diaion HP-20 (Supelco, Bellefonte, PA, USA) was used for open column chromatography. Escherichia coli beta-glucoronidais (G7396), PNPG (4-Nitrophenyl β-D-glucopyranoside, N7006), potassium phosphate monobasic (1551139), potassium phosphate dibasic (Potassium phosphate dibasic, 1551128), control group ( D-saccharic acid 1,4-lacone, S0375) was purchased from Sigma-Aldrich (USA).

1-2. Manufacture of extracts, fractions and compounds

An extract was obtained by repeatedly extracting 2.5 kg of the root of the plant with methanol in a reflux method three times. This extract was filtered with a Whatman filter paper and concentrated in a vacuum concentrator to obtain 666 g of a methanol extract from the root of the plant.

Thereafter, the methanol extract was turbid with 3 L of distilled water, and then fractionated with 100 g of dichloromethane, 40 g of ethyl acetate, and water, respectively, to obtain fractions.

Diaion HP-20 column chromatography was performed on the water fraction in a methanol-water gradient mixture (0:10 to 10:0) to obtain a fraction, which was then subjected to dichloromethane-methanol-water (7:1:0.05) single MPLC silica gel column chromatography was performed under solvent conditions to obtain 7 fractions (fraction 1 to fraction 7). From fraction 1, compounds No. 5 (7.5 mg) and No. 7 (10.3 mg) were separated by C-18 column chromatography under methanol-water (2:1) single solvent conditions, and Sephadex LH-20 from fraction 2. and methanol-water (1:1) as a single solvent, RP-C18 column chromatography was performed to separate compounds No. 2 (5 mg) and No. 3 (8.9 mg).

C-18 column chromatography, Sephadex LH-20 column chromatography, dichloromethane-methanol-water (2.5:1:0.1 ) Silica gel column chromatography was performed under single solvent conditions to separate compounds No. 6 (25 mg), No. 4 (18.7 mg), and No. 1 (7.8 mg). (156 mg), 9 (220.3 mg) and 10 (52.2 mg) compounds were isolated, and 11 (266.6 mg) and 12 (15.3 mg) compounds were isolated from fraction 5.

The name and nuclear magnetic resonance data ( ¹ H-NMR) of each compound are shown in Table 1, and compound No. 3 among them was named as Chemical Formula 1.

[Formula 1]

division structure designation ¹ H-NMR One

3′- O- ( O -methylferuloyl)sucrose
(400 MHz in MeOD-d4): δH 3.63 (d, J = 10.0 Hz), 3.67 (d, J = 9.0 Hz), 13C-NMR (100 MHz in MeOD-d4): δC 63.3 (C-1), 104.8 (C-2), 79.7 (C-3), 74.9 (C-4), 84.1 (C-5), 63.3 (C-6), 93.3 (C-1'), 73.1 (C-2') , 74.9 (C-3'), 71.2 (C-4'), 73.8 (C-5'), 65.3 (C-6'), 127.8 (C-1''), 112.1 (C-2'') , 149.5 (C-3''), 150.8 (C-4''), 116.5 (C-5''), 124.2 (C-6''), 115.1 (C-7''), 147.8 (C-7'') 8''), 168.5 (C-9''), 56.9 (-OMe). 2

sibiricose A5
(400 MHz in MeOD- d ₄ ): δ H 3.63 (d, J = 10.0 Hz), 3.67 (d, J = 9.0 Hz), ¹³ C-NMR (100 MHz in MeOD- d ₄ ): δ C 65.3 ( C-1), 104.8 (C-2), 79.7 (C-3), 74.6 (C-4), 84.1 (C-5), 63.3 (C-6), 93.3 (C-1'), 73.1 ( C-2'), 74.9(C-3'), 71.2(C-4'), 73.8(C-5'), 65.3(C-6'), 127.8(C-1''), 112.1(C -2''), 149.5(C-3''), 150.8(C-4''), 116.5(C-5''), 124.3(C-6''), 115.1(C-7'') , 147.8 (C-8″), 168.5 (C-9″), 56.5 (-OMe) 3

4- O -benzoyl-3′- O -( O -methylsinapoyl)sucrose
(400 MHz in MeOD- d ₄ ): δ H 3.63 (d, J = 10.0 Hz), 3.67 (d, J = 9.0 Hz), ¹³ C-NMR (100 MHz in MeOD- d ₄ ): δ C 65.6 ( C-1), 104.9 (C-2), 79.7 (C-3), 74.0 (C-4), 84.1 (C-5), 63.4 (C-6), 93.1 (C-1'), 73.1 ( C-2'), 74.9(C-3'), 71.6(C-4'), 72.5(C-5'), 65.3(C-6'), 131.5(C-1''), 106.9(C -2''), 154.9(C-3''), 141.4(C-4''), 154.9(C-5''), 106.9(C-6''), 147.4(C-7'') , 117.8 (C-8''), 168.9 (C-9''), 56.7 (3'', -OMe), 126.5 (C-1'''), 149.3 (C-2'''), 149.3 (C-3'''), 139.5(C-4'''), 149.3(C-5'''), 106.9(C-6'''), 147.4(C-7'''), 117.8 (C-8'''), 168.9 (C-9'''), 56.7 (3'', 5'', -OMe), 61.2 (4'', -OMe). 4

tenuifoliside A
(400 MHz in MeOD- d ₄ ): δ H 3.63 (d, J = 10.0 Hz), 3.67 (d, J = 9.0 Hz), ¹³ C-NMR (100 MHz in MeOD- d ₄ ): δ C 65.6 ( C-1), 104.8 (C-2), 79.3 (C-3), 74.1 (C-4), 84.2 (C-5), 63.7 (C-6), 92.6 (C-1'), 73.0 ( C-2'), 75.0 (C-3'), 71.4 (C-4'), 72.4 (C-5'), 65.6 (C-6'), 126.5 (C-1''), 106.9 (C -2''), 154.3(C-3''), 139.5(C-4''), 149.3(C-5''), 106.9(C-6''), 147.4(C-7'') , 115.7(C-8''), 168.3(C-9''), 56.7(3''-OMe), 126.5(C-1'''), 149.3(C-2'''), 149.3( C-3'''), 139.5(C-4'''), 149.3(C-5'''), 106.9(C-6'''), 147.4(C-7'''), 115.7( C-8'''), 169.2 (C-9'''), 56.5 (-OMe), 56.8 (-OMe). 5

6- O -( O -methyl- p -benzoyl)-3′- O -( O -methylsinapoyl)sucrose
(400 MHz in MeOD- d ₄ ): δ H 3.86(6H, s), 3.79(3H, s), ¹³ C-NMR (100 MHz in MeOD- d ₄ ): δ C 65.3(C-1), 104.8 (C-2), 79.8 (C-3), 74.6 (C-4), 84.2 (C-5), 63.7 (C-6), 92.6 (C-1'), 73.0 (C-2'), 75.0 (C-3'), 71.8 (C-4'), 72.4 (C-5'), 65.7 (C-6'), 131.3 (C-1''), 106.9 (C-2''), 154.6 (C-3''), 141.2 (C-4''), 154.6 (C-5''), 106.8 (C-6''), 147.3 (C-7''), 117.6 (C-8 ''), 167.9 (C-9''), 56.7 (3'', 5'', -OMe), 61.1 (4'', -OMe), 123.4 (C-1'''), 133.5 (C -2'''), 114.9(C-3'''), 165.3(C-4'''), 114.9(C-5'''), 132.9(C-6'''), 167.8(C -7'''), 56.0 (-OMe). 6

arillanin A
(400 MHz in MeOD- d ₄ ): δ H 3.63 (d, J = 10.0 Hz), 3.67 (d, J = 9.0 Hz), ¹³ C-NMR (100 MHz in MeOD -d ₄ ): δ C65.6 (C-1), 104.9 (C-2), 79.3 (C-3), 74.2 (C-4), 84.3 (C-5), 63.9 (C-6), 92.7 (C-1'), 73.1 (C-2'), 75.0 (C-3'), 71.9 (C-4'), 72.4 (C-5'), 65.6 (C-6'), 127.7 (C-1''), 112.1 ( C-2''), 149.5(C-3''), 150.8(C-4''), 116.5(C-5''), 124.3(C-6''), 147.4(C-7'') ), 115.0 (C-8''), 168.5 (C-9''), 56.5 (3''-OMe), 126.6 (C-1'''), 106.9 (C-2'''), 149.5 (C-3'''), 139.6(C-4'''), 149.5(C-5'''), 106.9(C-6'''), 115.8(C-7'''), 147.4 (C-8'''), 169.2 (C-9'''), 56.8 (OMe). 7

6,3′-di- O -sinapoylsucrose
(400 MHz in MeOD- d ₄ ) δ H3.63(d,J= 10.0 Hz), 3.67 (d, J = 9.0 Hz), ¹³ C-NMR(100 MHz in MeOD- d ₄ ): δC 65.5(C -1), 104.8 (C-2), 79.3 (C-3), 74.1 (C-4), 84.2 (C-5), 63.7 (C-6), 92.6 (C-1'), 72.9 (C -2'), 75.0(C-3'), 71.8(C-4'), 72.4(C-5'), 65.6(C-6'), 131.3(C-1''), 106.8(C-1'') 2''), 154.6(C-3''), 141.2(C-4''), 154.6(C-5''), 106.8(C-6''), 147.4(C-7''), 117.6 (C-8''), 167.9 (C-9''), 56.7 (3'', 5'', -OMe), 61.2 (4'', -OMe), 126.5 (C-1''' ), 106.8 (C-2'''), 149.3 (C-3'''), 139.4 (C-4'''), 149.3 (C-5'''), 106.8 (C-6''') ), 169.2 (C-7'''), 115.7 (C-8'''), 147.3 (C-9'''), 56.5 (-OMe), 56.8 (-OMe). 8

polygalasaponin XXXII
(600 MHz in MeOD- d ₄ ): δH 5.04(d, J = 8.0 Hz), 6.08 (d, J = 8.0 Hz), 5.81 (br s), 5.56 (br s), 5.26 (d, J = 8.0 Hz) 7.5 Hz), 6.09 (d, J = 3.0 Hz), 5.16 (d, J = 7.0 Hz), ¹³ C-NMR (150 MHz in MeOD- d ₄ ): δ C 105.4 (C-1', Glc), 95.0(C-1'', Fuc), 102.2(C-1''', Rha-1), 104.9(C-1'''', Rha-2), 104.8(C-1'''''', Xyl), 111.9 (C-1'''''''', Api), 105.5 (C-1''''''''', Ara); LC-MS m/z 1697.8 [M+Na]+ (calcd for C ₇₉ H ₁₁₈ NaO ₃₈ +, 1697.7), m/z 1673.9 [MH] ^- (calcd for C ₇₉ H ₁₁₇ O ₃₈ ^- , 1673.7). 9

micranthoside A
(600 MHz in MeOD- d ₄ ): δH 5.01(d, J = 8.0 Hz), 5.86 (d, J = 8.0 Hz), 6.32 (br s), 4.81 (d, J = 7.5 Hz), 4.87 ( d, J = 8.0 Hz), ¹³ C-NMR (150 MHz in MeOD- d ₄ ): δ C 104.1 (C-1', Glc), 94.0 (C-1'', Fuc), 100.9 (C-1''', Rha), 106.3 (C-1'''', Xyl), 106.3 (C-1'''', Gal); LC-MS m/z 1268.7 [M+NH ₄ ]+(calcd for C ₅₉ H ₉₈ NO ₂₈ ⁺ , 1268.6), m/z 1249.9 [MH] ^- (calcd for C ₅₇ H ₉₁ O ₂₈ -, 1249.5). 10

onjisaponin B
(600 MHz in MeOD- d ₄ ): δH 6.64 (d, J = 16.0 Hz), 7.13 (d, J = 9.0 Hz), 7.74 (d, J = 8.9 Hz), 7.88 (d, J = 16.0 Hz) ), ¹³ C-NMR (150 MHz in MeOD- d ₄ ): δ C 105.0 (C-1', Glc), 94.9 (C-1'', Fuc), 101.8 (C-1''', Rha- 1), 106.6 (C-1'''', Xyl), 104.2 (C-1'''', Gal), 104.5 (C-1''''', Rha-2); LC-MS m/z 1595.7 [M+Na] ⁺ (calcd for C ₇₅ H ₁₁₂ NaO ₃₅ ⁺ , 1595.6), m/z 1571.8 [MH] ^- (calcd for C ₇₅ H ₁₁₁ O ₃₅ ^- , 1571.6) 11

polygalasaponin XXVIII
(600 MHz in MeOD- d4 ): δ H5.06 (d, J = 8.0 Hz), 6.06 (d, J = 8.0 Hz), 6.40 (br s), 5.40 (d, J = 7.0 Hz), ¹³ C -NMR (150 MHz in MeOD- d ₄ ): δ C 105.4 (C-1', Glc), 94.8 (C-1'', Fuc), 101.2 (C-1''', Rha), 107.4 (C -1'''', Xyl); LC-MS m/z 1127.5 [M+Na] ⁺ (calcd for C ₅₃ H ₈₄ NaO ₂₄ ⁺ , 1127.5), m/z 1103.7 [MH] ^- (calcd for C ₅₃ H ₈₃ O ₂₄ ^- , 1103.7). 12

platycodin D
(600 MHz in C ₅ D ₅ N- d5 ): δ H 5.09 (d, J = 7.5 Hz), 5.67 (d, J = 3.7 Hz), 5.84 (d, J = 1.6 Hz), 6.26 (d, J = 2.4 Hz), 6.45 (d, J = 3.3 Hz), ¹³ C-NMR (150 MHz in C ₅ D ₅ N- d5 ): δ C 105.9 (C-1', Glc), 93.7 (C-1'', Ara), 101.0 (C-1''', Rha), 106.6 (C-1'''', Xyl), Api (C-1''''); LC-MS m/z 1247.6 [M+Na]+(calcd for C ₅₇ H ₉₂ NaO ₂₈ + , 1247.5), m/z 1223.7 [MH] ^- (calcd for C ₅₇ H ₉₁ O ₂₈ ^- , 1223.5).

Experimental Example 1. Confirmation of beta-gluconronidase inhibitory activity

In order to confirm the beta-gluconronidase inhibitory activity of the ginkgo biloba root extract, the fraction and the compound isolated therefrom of the present invention, beta-gluconronidase and the compound or solvent (methanol) under 0.1 mM phosphate buffer (pH 6.8) ), the pNPG substrate was added to the solution, and the analysis was performed based on the enzyme assay.

Specifically, beta-gluconronidase was prepared by dissolving it in 0.1 mM phosphate buffer at a concentration of 20 unit/mL. The methanol extract of Jiji root was prepared to be 100 μg/mL. Each compound was prepared at a concentration of 1 mM by dissolving in methanol for screening, and diluted to a final concentration of 100 μM to confirm the inhibitory activity. In addition, in order to calculate the IC ₅₀ value, 0.5, 0.25, 0.125, and 0.062 mM concentrations were prepared and used in the experiment. The pNPG substrate was prepared at a concentration of 1 mM by dissolving it in 0.1 mM phosphate buffer. After that, 130 μL of beta-gluconronidais, the methanol extract of the root of the plant, and 20 μL of each compound or methanol were added to a 96-well plate, and then 50 μL of 1 mM pNPG was further mixed. Thereafter, absorbance was measured at 405 nm wavelength using a reader (microplate reader, Multiskan GO, Thermo scientific,) at 37° C. for 20 minutes at 1 minute intervals.

D-saccharic acid 1,4-lacone was used as a positive control group, and beta-glucuronidase inhibitory activity was expressed as a ratio of the absorbance value of the extract or compound of the present invention to the absorbance value of the methanol-added group.

The inhibition rate of this experiment was calculated by Equation 1.

[Equation 1]

Inhibition rate (%) = [(ΔC/ΔS)/ΔC] × 100

(ΔC and ΔS are the difference between the measured value of methanol after 20 minutes of reaction and the measured value of each mixture with the extract or compound of the present invention)

As a result, as shown in Table 2 and FIG. 1, the methanol extract from the root of the plant showed 56.5% of beta-gluconronidase inhibitory activity. 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose of Formula 1, which is compound 3 among 12 compounds derived from fractions of extracts of the root extract of H. It was confirmed to have the highest inhibitory activity among the extracts and compounds.

division Inhibitory activity ^a
(%, 100 µM) One 25.7±3.5 2 12.0±4.1 3 74.9±2.6 (IC ₅₀ , 24.9±0.8 μM) 4 29.5±5.3 5 0.2±9.8 6 23.6±3.6 7 8.4±2.4 8 27.4±1.9 9 2.4±8.5 10 1.8±7.1 11 9.8±5.6 12 13.7±2.0 MeOH extract 56.5±4.5
(at 100 µg/mL) control group
(D-saccharic acid 1,4-lacone) 87.7±3.5 (IC ₅₀ , 19.6±2.4 μM)

Experimental Example 2. IC of 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose ₅₀ check value

Additionally, to check the IC ₅₀ value of 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose, the concentration of 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose was 6.25 to 50 Enzyme inhibition rates were measured when sequentially increased in μM. IC ₅₀ was calculated by Equation 2.

[Equation 2]

IC ₅₀ = y ₀ + [(a × x)/(b + x)]

(y ₀ =minimum value of the y-axis, a=maximum value of the y-axis, b=x value when the difference between the maximum and minimum values is 50%)

As a result, as shown in Figure 2, as the concentration of 4-O-benzoyl-3'-O- (O-methylsinapoyl) sucrose increases, the beta-gluconronidase inhibitory activity increases, and the IC ₅₀ value is 24.9 ± 0.8 μM confirmed to be

Experimental Example 3. Confirmation of non-competitive inhibitory properties of 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose

An experiment was performed to determine whether 4-O-benzoyl-3'-O-(O-methylsinapoyl)sucrose binds to beta-gluconronidases uncompetitively with the substrate. Since uncompetitive inhibitors bind to the enzyme-substrate complex, the inhibitory effect increases as the concentration of the substrate increases.

Specifically, enzyme kinetics were performed when 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose was 0 μM, 6.25 μM, 12.5 μM, 25 μM, and 50 μM, respectively. As a result, it was confirmed that 4-O-benzoyl-3'-O-(O-methylsinapoyl)sucrose acts as a non-competitive substrate inhibitor on beta-gluconronidais, as shown in FIG. 3 .

In addition, when 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose is 0 μM, 6.25 μM, 12.5 μM, 25 μM and 50 μM, respectively, the following Lineweaver-Burk equation (Equation 3) was applied to calculate the inhibition constant value.

[Equation 3]

1/v=(k _m /V _max [S])+(1+[I]/K _i )/V _max

(v = initial velocity, k _m = Michael-Menten constant (inhibition constant), V _max = maximum reaction rate, [S] = substrate concentration)

As a result, as shown in FIG. 4, the inhibition constant value (k _m ) was confirmed at a very low concentration of 13.4 μM.

Through these results, it was confirmed that 4-O-benzoyl-3'-O-(O-methylsinapoyl)sucrose can be used as a non-competitive inhibitor in the inhibitory composition of beta-gluconronidase.

Claims (29)

Raw paper ( Polygala tenuifolia ) A pharmaceutical composition for preventing or treating anticancer drug side effects, comprising an extract or a fraction thereof as an active ingredient.
According to claim 1,
The extract is water, C ₁ ~ C ₄ lower alcohol or a mixture thereof characterized in that the extraction as a solvent, a pharmaceutical composition.
According to claim 1,
The pharmaceutical composition, characterized in that the fraction is a dichloromethane fraction, an ethyl acetate fraction, a water fraction, or a fraction by a combination thereof.
A pharmaceutical composition for preventing or treating side effects of anticancer drugs, comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

According to claim 4,
The compound is a pharmaceutical composition for the prevention or treatment of side effects of anti-cancer drugs, which is isolated from the extract.
According to claim 1 or 4,
The anticancer agent is an antitumor antibiotic, a topoisomerase inhibitor or a taxane-based drug, characterized in that, a pharmaceutical composition for preventing or treating anticancer drug side effects.
According to claim 1 or 4,
The anticancer agents include irinotecan, camptothecin, novobiocin, epirubicin, dactinomycin, amsacrine, teniposide and eto Poside (etoposide) characterized in that at least one selected from, a pharmaceutical composition.
According to claim 1 or 4,
The side effect is characterized in that anorexia, vomiting, dyspnea, hair loss, diarrhea, hematopoietic toxicity, anemia, or neutropenia, a pharmaceutical composition.
According to claim 1 or 4,
The cancer is lung cancer, breast cancer, liver cancer, stomach cancer, colon cancer, colon cancer, rectal cancer, skin cancer, bladder cancer, prostate cancer, ovarian cancer, cervical cancer, small cell lung cancer, thyroid cancer, kidney cancer, fibrosarcoma, melanoma or blood cancer Characterized by a pharmaceutical composition.
According to claim 1 or 4,
The extract, a fraction thereof, or the compound is beta-glucuronidase ( β-glucuronidase ) Characterized in that, the pharmaceutical composition inhibits.
An anticancer adjuvant containing Polygala tenuifolia extract or a fraction thereof as an active ingredient.
An anticancer adjuvant comprising a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

According to claim 11 or 12,
The anticancer adjuvant is an anticancer adjuvant characterized in that for reducing, alleviating, suppressing or improving side effects caused by the administration of an anticancer agent.
According to claim 11 or 12,
The extract, a fraction thereof, or the compound is beta-glucuronidase ( β-glucuronidase ) characterized in that for inhibiting, anti-cancer adjuvant.
According to claim 11 or 12,
The cancer is lung cancer, breast cancer, liver cancer, stomach cancer, colon cancer, colon cancer, rectal cancer, skin cancer, bladder cancer, prostate cancer, ovarian cancer, cervical cancer, small cell lung cancer, thyroid cancer, kidney cancer, fibrosarcoma, melanoma or blood cancer Characterized by an anti-cancer adjuvant.
Raw paper ( Polygala tenuifolia ) A food composition for preventing or improving anticancer drug side effects comprising an extract or a fraction thereof as an active ingredient.
According to claim 16,
The extract is water, C ₁ ~ C ₄ lower alcohol or a mixture thereof characterized in that the extraction as a solvent, a food composition.
A food composition for preventing or improving side effects of anticancer drugs, comprising a compound represented by Formula 1 as an active ingredient.
[Formula 1]

The method of claim 16 or 18,
The composition is one or more formulations selected from the group consisting of tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bar health functional food formulations, beverages, gums and candies phosphorus, food composition.
Raw paper ( Polygala tenuifolia ) A food additive composition for preventing or improving anticancer drug side effects comprising an extract or a fraction thereof as an active ingredient.
According to claim 20,
The extract is water, C ₁ ~ C ₄ lower alcohol or a mixture thereof characterized in that the extraction as a solvent, food additive composition.
A food additive composition for preventing or improving side effects of anticancer drugs comprising a compound represented by Formula 1 as an active ingredient.
[Formula 1]

The method of claim 20 or 22,
The additive is one or more selected from the group consisting of sweeteners, flavors, preservatives, emulsifiers, acidulants and thickeners, food additive composition.
Raw paper ( Polygala tenuifolia ) Health functional food for preventing or improving the side effects of anticancer drugs containing an extract or a fraction thereof as an active ingredient.
A health functional food for preventing or improving side effects of anticancer drugs, comprising a compound represented by Formula 1 as an active ingredient.
[Formula 1]

The method of claim 24 or 25,
The health functional food is one or more formulations selected from the group consisting of tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bar health functional food formulations, beverages, gums and candies It will be, health functional food.
Raw paper ( Polygala tenuifolia ) A feed composition for preventing or improving anti-cancer drug side effects comprising an extract or a fraction thereof as an active ingredient.
The method of claim 27,
The extract is water, C ₁ ~ C ₄ lower alcohol or mixtures thereof characterized in that the extraction as a solvent, feed composition.
A feed composition for preventing or improving side effects of anticancer drugs comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

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