KR102679960B1 - 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 improving the side effects of anticancer drugs, comprising as an active ingredient a root extract, a fraction thereof, or a compound isolated therefrom.
The raw extract, fractions thereof, or compounds isolated therefrom according to the present invention reduce the side effects caused by anticancer drugs by inhibiting the activity of beta-glucuronidase, and can be usefully used as a composition for preventing or improving 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 the side effects of anticancer drugs, comprising as an active ingredient a root extract, a fraction thereof, or a compound isolated therefrom.

Anticancer drugs are chemotherapy treatments used to inhibit the proliferation of cancer cells. It is used in a broad sense as a treatment used before and after surgery to suppress micro-metastasis of cancer in order to increase the success of surgical operations, or to prevent recurrence, prolong the survival period of terminally ill patients, or relieve symptoms.

When cancer is discovered, in the case of advanced cancer, chemotherapy is performed to treat cancer using anticancer drugs, and anticancer drugs are considered an essential means of treating cancer. However, loss of appetite, nausea, and vomiting may occur during or for several days after the administration of anticancer drugs, and hypersensitivity reactions (skin rash, angioedema, and breathing difficulties) may occur immediately and within a few hours of anticancer drug administration. Additionally, 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, colon cancer, small cell lung cancer, cervical cancer, rectal cancer, colon cancer, and ovarian cancer, and blocks specific enzymes required for cell division and DNA restoration to prevent cancer cells. It is a topoisomerase inhibitor that kills. Even in the case of irinotecan, which is widely used, side effects such as diarrhea appear after taking it.

Therefore, efforts are continuing to minimize these side effects, and as part of these efforts, research is being conducted to minimize the side effects of cancer using natural products.

Meanwhile, Polygala tenuifolia is a dicotyledonous plant in the Polygalactyae family, growing in the low mountainous areas north of central Korea. Wonji has excellent expectorant and mental stabilizing effects, and is known to be effective in improving forgetfulness, heart palpitations, insomnia, and cognitive impairment.

However, research on the effectiveness of Wonji in alleviating the side effects of anticancer drugs is still insufficient.

Under this background, the present inventors have made diligent efforts to develop natural materials useful for reducing the side effects of anticancer drugs. As a result, we have confirmed the effectiveness of extracts, fractions, or compounds isolated therefrom in reducing the side effects of anticancer drugs, demonstrating their applicability as materials for improving the side effects of anticancer drugs. After confirmation, the present invention was completed.

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

The present invention aims to solve the above-described problems and other problems associated therewith.

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

Another exemplary object of the present invention is to provide a pharmaceutical composition for preventing or treating side effects of anticancer drugs, which contains a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

Another exemplary object of the present invention is to provide an anticancer adjuvant containing 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, which contains the compound represented by Formula 1 above as an active ingredient.

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

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

Another exemplary object of the present invention is to provide a feed 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 feed composition for preventing or improving anticancer drug side effects, which contains 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 other problems not mentioned can be clearly understood by those skilled in the art from the description below. There will be.

This is explained in detail as follows. Meanwhile, each description and embodiment disclosed in the present application may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this application fall within the scope of this application. Additionally, the scope of the present application cannot be considered limited by the specific description described below.

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

The term "Wonji" of the present invention is a plant of the dicotyledonous plant Apiaceae family, and is an herbal medicine that has been used for hundreds of years to increase memory, stabilize emotions, and improve sleep and cognitive disorders.

The term "anticancer drug side effects" in the present invention refers to negative effects that occur incidentally other than treatment that may occur due to the administration of anticancer drugs, and includes phenomena such as loss of appetite, vomiting, difficulty breathing, hair loss, or diarrhea. It also includes hematopoietic toxicity, anemia, and neutropenia induced by anticancer drugs. In the present invention, the side effect may be diarrhea.

In the present invention, cancer includes lung cancer, breast cancer, liver cancer, stomach 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, but is not limited to, blood cancer.

The term "anticancer agent" in the present invention refers to all chemotherapy regimens 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 anti-tumor antibiotics include actinomycin D, bleomycin sulfate, daunomycin, daunorubicin, doxorubicin, epirubicin ( It is preferable to use 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, and amsacrine. ), teniposide, and etoposide.

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

In the present invention, the raw material extract or its fraction can inhibit beta-glucuronidase .

Beta-glucuronidase is a sugar hydrolyzing enzyme found in milk tissues, body fluids, microorganisms, plants, and seaweed. Bacterial beta-glucuronidase expressed in human intestinal microorganisms (Escherichia coli) is up to The two monomers, which are 45% similar in base sequence and contain 597 amino residues, have an asymmetric structure.

Irinotecan, an anticancer drug, is hydrolyzed by human carboxylesterases and converted into the active SN-38 (7-ethyl-10hydroxycamptothecin). SN-38 has an anti-tumor effect by inhibiting human topoisomerase I, and is biosynthesized into SN38-glucuronide by UDP-glucuronosyl transferases in the liver or tissues. . Afterwards, SN38-glucuronide excreted into the intestines is hydrolyzed back to SN38 by bacterial beta-glucuronidase, which damages intestinal epithelial cells and induces diarrhea. Therefore, by inhibiting beta-glucoronidase, hydrolysis of the metabolite to SN38 can be prevented, thereby reducing the phenomenon of diarrhea induced by irinotecan.

Specifically, in the experimental example of the present invention, it was confirmed that the compound isolated from the raw paper extract and the fraction of the raw paper extract inhibited the activity of beta-glucoronidase, and based on this, the raw paper extract, the fraction, or the compound isolated therefrom of the present invention was confirmed. It was confirmed that the compound can be useful in alleviating diarrhea caused by taking irinotecan, an anticancer drug, by inhibiting the activity of beta-glucoronidase.

The term "extract" in the present invention refers to the extract itself, such as an extract obtained by extraction treatment of the raw material, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a crude product or purified product of the extract, or a mixture thereof, etc. and extracts of all formulations that can be formed using the extract.

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

The extract of the present invention is obtained by extracting the raw material 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 can 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 solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, and dichloromethane;　Alternatively, a mixture thereof may be used. For example, it may be a solvent selected from the group consisting of water, lower alcohols having 1 to 4 carbon atoms, or mixed solvents thereof.

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

The term "prevention" of the present invention refers to all actions that suppress or delay the side effects of anticancer drugs through the 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. It refers to any action that improves, alleviates, or changes side effects to advantage. The term “improvement” of the present invention refers to any action in which anticancer drug side effects are improved by administration of the composition.

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

In the present invention, the fractionation method for obtaining the above 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 with a certain molecular weight cut-off value, a chromatography fractionation method, and a combination thereof. Additionally, the type of solvent used to obtain the above fraction in the present invention is not particularly limited, and any solvent known in the art can be used. Examples of the fractionation solvent include nucleic acid, dichloromethane, ethyl acetate, butanol, water, organic solvent, or a mixed solvent thereof.

In the present invention, the fraction may be obtained by a solvent fractionation method of treating the raw extract with a solvent, and the fraction obtained by the solvent fractionation method may be obtained by fractionating the fraction obtained by the chromatography fractionation method. For example, after fractionating the raw extract into dichloromethane, ethyl acetate, and water layers, column chromatography can be performed on the water fraction to obtain another fraction.

In 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 the following formula (1) 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 the raw material, for example, it may be obtained by performing chromatography from a fraction of the raw material 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, and specifically, it has the formula 1 below: It may be indicated as 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose.

[Formula 1]

In the present invention, the pharmaceutically acceptable salt includes an acid addition salt formed with 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, 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 it from These pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and nitrate. Odide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, sube. Latex, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate , methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylene sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate. Includes nitrate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate, etc.

The acid addition salt according to the present invention can be prepared by conventional methods, 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 is beta -Can act as a non-competitive inhibitor of glucuronidase. A non-competitive inhibitor is a substance that binds to a complex of a substrate and an enzyme and inhibits the activity of the enzyme. Even if the concentration of the substrate is high, the inhibitory effect is not offset or reduced.

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

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

The term “pharmaceutical composition” of the present invention refers to a product prepared for the purpose of preventing or treating disease, and can be formulated and used in various forms according to conventional methods.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent according to a conventional method. Pharmaceutically acceptable carriers are well known in the art depending on the administration route or dosage form, and for specifics, each country's pharmacopoeia, including the 'Korean Pharmacopoeia', can be referred to. 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, Examples include, but are not limited to, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Additionally, carriers, excipients, and diluents that may be included in the composition of the present invention may be unnatural carriers, but are not limited thereto.

The pharmaceutical composition of the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, or sterile injectable solutions according to conventional methods. . In detail, it can be prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are made by adding at least one excipient to the compound, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be prepared by mixing. Additionally, in addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, they contain various excipients such as wetting agents, sweeteners, fragrances, and preservatives. You can. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, Withepsol, Macrogol, Tween 61, cacao, laurin, glycerogelatin, etc. can be used. Regarding the specific formulation of pharmaceutical compositions, it is known in the art, and references can be made to, for example, Remington's Pharmaceutical Sciences (19th ed., 1995). The above documents are considered a part of this specification.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The pharmaceutically effective amount refers to an amount that is sufficient to treat the disease at a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects. The effective dose level refers to the patient's health status, type and severity of the disease, It can be determined based on factors including the activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, drugs combined or used simultaneously, and other factors well known in the medical field. The dosage and frequency of administration do not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, dogs, cats, cows, horses, pigs, and humans through various routes, and humans may be preferable. All modes of administration are contemplated and may include, but are not limited to, oral, intravenous, intramuscular or subcutaneous injection.

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

The term "including as an active ingredient" in the present invention means that the pharmaceutical composition contains an effective amount that can prevent or treat the side effects of anticancer drugs.

In another aspect of the present invention, the present invention provides an anti-cancer adjuvant containing an extract or a fraction thereof as an active ingredient.

In 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, etc. caused by anticancer drug administration.

In another aspect of the present invention, the present invention provides a food composition for preventing or ameliorating side effects of anticancer 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 manufactured in various types of formulations, and unlike general drugs, it has the advantage of being made from food as a raw material and having no side effects that may occur when taking the drug for a long period of time. The food composition of the present invention can be manufactured in any form, and specifically, health functional food preparations such as tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, etc. It may be one or more formulations selected from the group consisting of beverages, gums, and candies, but is not particularly limited thereto.

Additionally, the food composition of the present invention may contain food additives in addition to the active ingredients. Food additives can generally be understood as substances that are added to, mixed with, or infiltrated into food when manufacturing, processing, or preserving food. Since they are consumed daily and for a long period of time with food, their safety must be guaranteed. The food additives are classified into sweeteners, flavorants, preservatives, emulsifiers, acidulants, thickeners, etc. in terms of function, and are not particularly limited as long as they meet the purpose to be achieved by the food composition of the present invention. In addition, the food composition of the present invention may contain, in addition to the food additives, bioactive substances or minerals known in the art for the purpose of functionality and nutritional supplementation and whose safety is guaranteed as food additives. The physiologically active substances or minerals are not particularly limited as long as they meet 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 depending on the product type, and with respect to other food additives that may be included in the food composition of the present invention, each country's food code You can also refer to the Food Additives Code.

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

In 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 a raw 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 by adding, mixing, infiltrating, or other methods to food for the purpose of improving preservability, improving quality, enhancing nutrition, improving flavor and appearance when manufacturing, processing, or preserving food. It can mean a substance that becomes The food additive can be added as is with the active ingredient of the present invention or used together with other food or food ingredients, and the mixing amount of the active ingredient can be appropriately determined by a person skilled in the art depending on the purpose of use.

Food additives with guaranteed safety are limited in terms of ingredients or functions in the Food Additives Code in accordance with each country's laws governing the manufacture and distribution of food ('Food Sanitation Act' in Korea). In the Korea Food Additive Code (Ministry of Food and Drug Safety Notification 'Food Additive Standards and Specifications'), food additives are classified into chemical synthetics, natural additives, and mixed preparations in terms of composition. These food additives are classified in terms of function as sweeteners and flavors. It is classified into preservatives, emulsifiers, acidulants, thickeners, etc.

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

The flavoring agent can be used to improve taste or aroma, and both natural and synthetic agents can be used. Preferably, natural products are used. When using natural products, they can serve the purpose of enhancing nutrition in addition to flavor. Natural flavoring agents may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, etc., or may be obtained from green tea leaves, coriander leaves, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, etc. You can also use things obtained from ginseng (red ginseng), bamboo shoots, aloe vera, and ginkgo nuts. Natural flavoring agents may be liquid concentrates or solid extracts. In some cases, synthetic flavoring agents may be used, and as synthetic flavoring agents, esters, alcohols, aldehydes, terpenes, etc. may be used.

The preservatives include calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc., and emulsifiers include acacia gum, carboxymethylcellulose, xanthan gum, Pectin, etc. can be used, and as acidulants, acidic acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, etc. can be used. In addition to improving taste, acidulants may be added to ensure that the food composition has an appropriate acidity for the purpose of suppressing the growth of microorganisms.

As the thickening agent, a suspending agent, settling agent, gel forming agent, bulking agent, etc. may be used.

The food additive composition containing the raw extract or fraction thereof of the present invention can achieve the effect of preventing or improving anticancer drug side effects in addition to the added food ingredient.

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

In another aspect of the present invention, the present invention provides a health functional food for preventing or improving the side effects of anticancer drugs containing a root 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 with functional properties useful to the human body. The term “functionality” refers to obtaining effects useful for health purposes, such as controlling nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be manufactured by a method commonly used in the industry, and can be manufactured by adding raw materials and components commonly added in the industry during production.

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

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

In another aspect of the present invention, the present invention provides a feed composition for preventing or improving the side effects of anticancer drugs, comprising a raw 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 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 feed additives. 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 a component of the meal, especially for or suitable for eating, ingestion, and digestion by animals.

The type of feed is not particularly limited, and feed commonly used in the art can be used. Non-limiting examples of the feed include plant feeds such as grains, roots and fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, cucurbits or grain by-products; Examples include animal feeds such as proteins, inorganic substances, fats and oils, minerals, fats and oils, single-cell proteins, zooplanktons or foods. These may be used individually or in combination of two or more types.

The raw extract, fractions thereof, or compounds isolated therefrom according to the present invention reduce the side effects caused by anticancer drugs by inhibiting the activity of beta-glucuronidase, and can be usefully used as a composition for preventing or improving the side effects of anticancer drugs.

Figure 1 shows the results showing the beta-glucuronidase inhibitory activity of compounds isolated from fractions of the raw extract.
Figure 2 shows the results showing the beta-glucuronidase inhibitory activity of the compound of Formula 1 at different concentrations.
Figure 3 shows the results of enzyme kinetics of the compound of Formula 1.
Figure 4 shows the low-resolution 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 Hoji root extracts, fractions and compounds

1-1. experiment 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 using Kieselgel 60 F254 and PR-18 F254s plates (Merck, USA). The sample was immersed in 10% (v/v) H2SO4 (Aldrich, USA) solvent and then dried with dry air at 300°C 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-glucoronidase (G7396), PNPG (4-Nitrophenyl β-D-glucopyranoside, N7006), Potassium phosphate monobasic (1551139), Potassium phosphate dibasic (1551128), control group ( D-saccharic acid 1,4-lacone, S0375) was purchased from Sigma-Aldrich (USA).

1-2. Preparation of extracts, fractions and compounds

An extract was obtained by repeatedly extracting 2.5 kg of the roots with methanol in a reflux method three times. This extract was filtered through Whatman filter paper and then concentrated using a reduced pressure concentrator to obtain 666 g of methanol extract of Hoji root.

Afterwards, the methanol extract was turbidized 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.

The water fraction was subjected to Diaion HP-20 column chromatography using 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). MPLC silica gel column chromatography was performed under solvent conditions to obtain seven fractions (fractions 1 to 7). Compounds 5 (7.5 mg) and 7 (10.3 mg) were separated from fraction 1 by C-18 column chromatography under methanol-water (2:1) single solvent conditions, and Sephadex LH-20 from fraction 2. Compounds No. 2 (5 mg) and No. 3 (8.9 mg) were separated by performing RP-C18 column chromatography under single solvent conditions of methanol-water (1:1).

From fraction 3, C-18 column chromatography, Sephadex LH-20 column chromatography, and dichloromethane-methanol-water (2.5:1:0.1) solvent conditions were acetone-water (1:1, 2:1, 3:1). ) Compounds No. 6 (25 mg), No. 4 (18.7 mg), and No. 1 (7.8 mg) were separated by performing silica gel column chromatography under single solvent conditions, and No. 8 was separated from fraction 4 in the same manner as fraction 3. (156 mg), 9 (220.3 mg), and 10 (52.2 mg) compounds were isolated, and compounds 11 (266.6 mg) and 12 (15.3 mg) were isolated from fraction 5.

The name and nuclear magnetic resonance data ( ^1H -NMR) of each compound are shown in Table 1, and compound number 3 was named as Formula 1.

[Formula 1]

division structure designation ^1H -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- 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- 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 ): δ H 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 = 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 ): δ H 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 -d4 ): 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-glucoronidase inhibitory activity

In order to confirm the beta-glucuronidase inhibitory activity of the root extract, fraction, and compound isolated therefrom of the present invention, beta-glucuronidase and the compound or solvent (methanol) were incubated in 0.1 mM phosphate buffer (pH 6.8) at 37°C. ) pNPG substrate was added to the solution containing and analysis was performed based on enzyme assay.

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

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

The inhibition rate in this experiment was calculated using 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 Figure 1, the methanol extract of Hoji root showed a beta-glucuronidase inhibitory activity of 56.5%. Among the 12 compounds derived from the fractions of the root extract, compound number 3, 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose of Formula 1, showed beta-glucuronidase inhibitory activity of 74.9%, It was confirmed to have the highest inhibitory activity among all 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 confirm 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. The enzyme inhibition rate was measured when sequentially increasing in μM. IC ₅₀ was calculated using 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 50% of the difference between the maximum and minimum values)

As a result, as shown in Figure 2, as the concentration of 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose increases, the beta-glucuronidase inhibitory activity increases, and the IC ₅₀ value is 24.9±0.8 μM. It was confirmed that it was.

Experimental Example 3. Confirmation of non-competitive inhibition 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-glucuronidase in an uncompetitive manner. Since non-competitive inhibitors bind to a complex of enzyme and substrate, they have the advantage that the inhibitory effect increases as the concentration of the substrate increases.

Specifically, enzyme kinetics studies 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 on beta-glucuronidase as a non-competitive inhibitor for the substrate, as shown in Figure 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 Lineweaver-Burk equation is as follows: (Equation 3) was applied to calculate the low-resolution constant value.

[Equation 3]

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

(v = initial speed, k _m = Michael-Menten constant (low resolution constant), V _max = maximum reaction speed, [S] = substrate concentration)

As a result, as shown in Figure 4, the low resolution constant value (k _m ) was confirmed to be a very low concentration of 13.4 μM.

These results confirmed that 4-O-benzoyl-3′-O-(O-methylsinapoyl)sucrose can be used as a beta-glucuronidase inhibitor as a non-competitive inhibitor.

Claims (29)

A pharmaceutical composition for preventing or treating side effects of anticancer drugs, comprising Polygala tenuifolia extract or a fraction thereof as an active ingredient,
A pharmaceutical composition, wherein the side effect is diarrhea.
According to paragraph 1,
A pharmaceutical composition, characterized in that the extract is extracted using water, a lower alcohol of C ₁ to C ₄ , or a mixture thereof as a solvent.
According to paragraph 1,
A pharmaceutical composition, characterized in that the fraction is a dichloromethane fraction, an ethyl acetate fraction, a water fraction, or a combination thereof.
According to paragraph 1,
A pharmaceutical composition for preventing or treating side effects of anticancer drugs, wherein the raw extract contains a compound represented by the following formula (1).
[Formula 1]

delete According to paragraph 1,
A pharmaceutical composition for preventing or treating side effects of anticancer drugs, wherein the anticancer agent is an antitumor antibiotic, a topoisomerase inhibitor, or a taxane-based drug.
According to paragraph 1,
The anticancer drugs include irinotecan, camptothecin, novobiocin, epirubicin, dactinomycin, amsacrine, teniposide, and etho. A pharmaceutical composition, characterized in that it contains at least one selected from etoposide.
delete According to paragraph 1,
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 pharmaceutical composition.
According to paragraph 1,
The extract or fraction thereof is a pharmaceutical composition, characterized in that it inhibits beta -glucuronidase.
An anticancer supplement containing polygala tenuifolia extract or a fraction thereof as an active ingredient.
According to clause 11,
An anti-cancer adjuvant, wherein the raw extract contains a compound represented by the following formula (1).
[Formula 1]

According to clause 11,
The anti-cancer adjuvant is an anti-cancer adjuvant that reduces, alleviates, suppresses or improves side effects caused by the administration of anti-cancer drugs.
According to clause 11,
The extract or fraction thereof is an anti-cancer adjuvant, characterized in that it inhibits beta -glucuronidase.
According to clause 11,
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 anti-cancer adjuvant.
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,
The composition, wherein the side effect is diarrhea.
According to clause 16,
A food composition, characterized in that the extract is extracted using water, a lower alcohol of C ₁ to C ₄ , or a mixture thereof as a solvent.
According to clause 16,
A food composition for preventing or improving side effects of anticancer drugs, wherein the raw extract contains a compound represented by the following formula (1).
[Formula 1]

According to clause 16,
The composition is one or more dosage forms selected from the group consisting of tablets, capsules, pills, granules, liquid, powder, flakes, paste, syrup, gel, jelly, bars, health functional food preparations, beverages, gums, and candies. Phosphorus, food composition.
A food additive composition for preventing or improving the side effects of anticancer drugs containing Polygala tenuifolia extract or a fraction thereof as an active ingredient,
The composition, wherein the side effect is diarrhea.
According to clause 20,
The extract is a food additive composition, characterized in that it is extracted using water, C ₁ to C ₄ lower alcohol, or a mixture thereof as a solvent.
According to clause 20,
A food additive composition for preventing or improving side effects of anticancer drugs, wherein the raw extract contains a compound represented by the following formula (1).
[Formula 1]

According to clause 20,
The food additive composition, wherein the additive is at least one selected from the group consisting of sweeteners, flavors, preservatives, emulsifiers, acidulants, and thickeners.
A health functional food for preventing or improving the side effects of anticancer drugs containing polygala tenuifolia extract or fractions thereof as an active ingredient,
A health functional food, characterized in that the side effect is diarrhea.
According to clause 24,
The raw extract is a health functional food for preventing or improving side effects of anticancer drugs, which includes a compound represented by the following formula (1).
[Formula 1]

According to clause 24,
The health functional food is one or more dosage forms selected from the group consisting of health functional food preparations such as tablets, capsules, pills, granules, liquid, powder, flakes, paste, syrup, gel, jelly, bars, beverages, gums, and candies. It is a health functional food.
A feed composition for preventing or improving the side effects of anticancer drugs containing polygala tenuifolia extract or fractions thereof as an active ingredient,
A composition wherein the side effect is diarrhea.
According to clause 27,
The extract is a feed composition, characterized in that the extract is extracted using water, a lower alcohol of C ₁ to C ₄ or a mixture thereof as a solvent.
According to clause 27,
A feed composition for preventing or improving anticancer drug side effects, wherein the raw extract contains a compound represented by the following formula (1).
[Formula 1]