WO2002052956A1

WO2002052956A1 - Antitumor food or beverage

Info

Publication number: WO2002052956A1
Application number: PCT/JP2001/011374
Authority: WO
Inventors: Gou Shinohara; Noriyasu Kuno; Toshiyuki Inui
Original assignee: The Nisshin Oillio, Ltd.
Priority date: 2000-12-27
Filing date: 2001-12-25
Publication date: 2002-07-11
Also published as: JPWO2002052956A1

Abstract

An antitumor food or beverage which contains as the active ingredient a compound selected among maslinic acid, erythro diols, ursolic acid, uvaol, betulinic acid, betulin, physiologically acceptable salts of these, and derivatives of these.

Description

Description Anti-tumor food and drink Background of the invention

The present invention relates to anticancer foods and drinks containing a compound selected from specific pentacyclic triterpenes and their physiologically acceptable salts or their derivatives. (1997) continued its upward trend, and in the United States (1995), it was on a downtrend, but it is still the second leading cause of death.

To date, various treatments for cancer have been cited, mainly surgery and chemotherapy, etc. However, the treatment results have definitely improved. However, with the progress of an aging society, the number of cancer deaths will continue to increase in the current state, and it is estimated that it will exceed 400,000 in 21015.

On the other hand, considering QOL (Qua1 ityofLife: quality of life) in life, it is desirable to promote cancer prevention through lifestyle habits that promote health. At the center of such measures is the improvement of eating habits, and various proposals have been made so far. Numerous patents have been published for antitumor foods and drinks that have stated a prophylactic or early therapeutic effect on cancer. However, the functional foods and health foods for cancer that have been proposed so far have had any problems such as effectiveness, price, and stable supply.

On the other hand, in recent years, research on pharmacologically functional substances in various plants, including medicinal plants, has been actively conducted at research institutes of universities, public and private research institutes, and private research institutes. Among the functional triterpenes, especially for oleanolic acid, ursolic acid, and diphosphoric acid, the inhibitory effect on carcinogenesis promotion was reported by academic societies in the literature, introduced in newspapers, magazines, etc. and patented. Proposals have been made. In particular, with respect to foods and drinks that have been shown to suppress tumor promoters, a beverage composition having a tumor promoter suppressive effect with respect to oleanolic acid and persolic acid has been published (Japanese Patent Publication No. 64-399973).

However, these pentagonal triterpenes have a tumor cell growth inhibitory effect, tumor cell killing effect and tumor cell metastasis inhibitory effect on tumor cells that have already developed, and can be taken orally through forms such as food and drink. However, it has not been known that the effect can be fully enjoyed. Disclosure of the invention

It is an object of the present invention to provide an antitumor food and drink having a very excellent antitumor effect capable of preventing or treating tumor growth and metastasis. It is an object of the present invention to provide an anti-tumor food and drink which can be enjoyed easily and in a safe manner.

The present inventors have conducted intensive studies to achieve the above object, and as a result, it has been found that specific pentagonal triterpenes and their physiologically acceptable salts or their derivatives are excellent in suppressing tumor cell growth. The present invention has been found to have an effect, a tumor cell killing effect and an inhibitory effect on tumor cell metastasis, and that, by ingesting them orally in the form of food or drink, the antitumor effect can be sufficiently enjoyed. It was completed. That is, the present invention provides a compound which is effective for a compound selected from maslinic acid, erythrodiol, ursolic acid, peroxyl, vellic acid, perrin and their physiologically acceptable salts, and derivatives thereof. Provided is an antitumor food / drink which is contained as an ingredient. The present invention also provides, as an active ingredient, a compound selected from maslinic acid, erythrodiol, ursolic acid, dibasic acid, dibasic acid, diphosphoric acid, a physiologically acceptable salt thereof, and a derivative thereof. Provided is a food or drink for suppressing tumor cell proliferation.

The present invention also provides, as an active ingredient, a compound selected from maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin and a physiologically acceptable salt thereof, or a derivative thereof. Provided is a food and drink for killing tumor cells.

Here, as for maslinic acid, erythrodiol, ursolic acid, polyvinyl alcohol, veric acid, and phosphorus, it is possible to use those extracted from natural raw materials or artificial synthetic products. Can also. Similarly, as for these physiologically acceptable salts and derivatives, those extracted from natural raw materials and synthetic products obtained by performing synthetic reactions using these as raw materials can be used.

Examples of foods and drinks include various kinds of foods and drinks such as confectionery, processed foods, prepared fats and oils, processed fats and oils, dairy products, and beverages. The shape and properties of the food and drink of the present invention are not particularly limited, and may be any of solid, semi-solid, gel, liquid, and powder. Since the pentacyclic triterpenes and rosin or specific derivatives thereof are generally fat-soluble, it can be said that this is a particularly preferable form when the food or drink is a prepared oil or fat or a processed oil or fat. Furthermore, foods and drinks obtained by using the prepared oil or fat or processed oil or fat as a raw material, or using it for fried or stir-fried foods are also preferable.

Further, as the food and drink of the present invention, an aqueous food and drink such as a beverage can also be obtained. In particular, by making a part or all of the specific pentacyclic triterpenes into a physiologically acceptable salt thereof and / or a specific derivative thereof, the lipophilic pentacyclic triterpenes can be converted to a water-soluble pentacyclic triterpene. This is preferable because

The present invention also relates to maslinic acid, erythrodiol, ursolic acid, ebaol, Provided is a food or beverage for tumor prevention and a food or beverage for tumor prevention comprising a compound selected from the group consisting of phosphoric acid, betaline and physiologically acceptable salts thereof, and derivatives thereof. I do.

The present invention is also selected from the group consisting of maslinic acid, erythritol, ursolic acid, evanol, diphosphoric acid, berulin and their physiologically acceptable salts, or derivatives thereof. The present invention also provides a food and drink for treating tumors and a use as food and drink for treating tumors, comprising a compound. BEST MODE FOR CARRYING OUT THE INVENTION

The present invention comprises a compound selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, baioruul, berylic acid, berylin and physiologically acceptable salts thereof, or derivatives thereof. More particularly, the present invention relates to a food and drink for suppressing tumor cell proliferation, a food and drink for killing tumor cells, and a food and drink for suppressing tumor cell metastasis. Maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, bellin and their physiologically acceptable salts, or their derivatives can be obtained by extraction from plants naturally. Some of them can be artificially synthesized, and any of them can be suitably used. The term “containing as an antitumor component” means that the antitumor component is contained to such an extent that the desired tumor cell growth inhibitory effect, tumor cell killing effect, tumor cell metastasis inhibitory effect and the like can be obtained.

Maslinic acid, erythrodiol, persolic acid, berylic acid, and berylin have an anti-carcinogenic promoter activity and are known to suppress carcinogenesis, and are expected to suppress the development of cancer cells. I have. The food and drink of the present invention suppresses the proliferation of tumor cells at an undetectable level that has already occurred and kills them and suppresses metastasis. Since it also has the effect of eliminating tumors, it can be used as a food or drink for tumor prevention such as suppression of tumor growth. it can. In addition, it can be used as a food or drink for tumor treatment that suppresses the growth of tumor cells, kills them, and suppresses metastasis immediately after the tumor cells develop, that is, stops tumor progression and eliminates the tumor. .

The food and drink of the present invention have antitumor effects such as a tumor cell growth inhibitory effect, a tumor cell killing effect, and a tumor cell metastasis inhibitory effect. These antitumor effects are evaluated by continuous ingestion. The effect can also be evaluated by a test method using cultured cancer cells. According to these evaluation methods, they have an extremely excellent antitumor effect even when compared with oleanolic acid or the like, which is known as a tumor-promoting promoter-suppressing active substance.

Tumors of interest in the present invention include swelling and true tumors, including benign and malignant tumors. Specifically, astrocytoma · glioblastoma · medulloblastoma · oligodendroglioma · ependymoma · glioma such as choroid papilloma · meningiomas · pituitary adenoma · schwannoma · congenital tumor · Brain tumors such as metastatic brain tumors, squamous cell carcinoma · Lymphoma · Various adenomas and nasopharyngeal cancer caused by them · Oropharyngeal cancer 頭 Pharyngo-pharyngeal cancer, etc. Mesothelioma · Peritoneal mesothelioma · Mesothelioma such as pericardial mesothelioma, thoracic duct cancer · Lobular carcinoma ■ Breast cancer such as papilloma, small cell carcinoma · Adenocarcinoma · Squamous cell carcinoma · Large Cell carcinomaLung cancer such as glandular squamous cell carcinoma, gastric cancer, cervical esophageal cancerChest esophageal cancerEsophageal cancer such as abdominal esophageal cancer, rectal cancer-

Sigmoid colon cancer · Ascending colon cancer · Transverse colon cancer · Cecal cancer 大 Colorectal cancer such as descending colon cancer, hepatocellular carcinoma · Intrahepatic ductal carcinoma · Hepatoblastoma · Hepatic duct 囊Liver cancer such as adenoid cancer, Teng cancer, Insulinoma's gastrinoma · Endocrine tumors such as VIP-producing adenoma, extrahepatic hepatic ductal carcinoma, liver sac cancer, penis cancer, renal pelvis Ureteral cancer, urethral cancer, renal cell carcinoma · ゥ Ilmus tumor · Kidney cancer such as renal angiomyolipoma, seminoma · fetal carcinoma · yolk cystoma · Choriocarcinoma 精 testis such as teratoma ) Tumor or germ cell tumor, prostate cancer, bladder cancer, vulvar cancer, cervical cancer, uterine body cancer, uterine cancer such as endometrial cancer, uterine sarcoma, uterine fibroids, villi Sexual disease, vaginal cancer, undifferentiated germ cell tumor · Yolk sac tumor · Immature teratoma · Ovarian germ cell tumors such as cystic cyst cancer · Ovarian tumors such as ovarian cancer, nevus cells · Mela Caused by melanomas such as fleas, cutaneous lymphomas such as mycosis fungoides, and skin cancer precursors Skin cancer such as squamous cell carcinoma, fibrous histiocytoma, liposarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, schwannomas, hemangiosarcoma, fibrous Sarcoma · Neurofibrosarcoma · Hemangiopericytoma · Soft tissue sarcoma such as alveolar soft tissue sarcoma, Hodgkin's lymphoma · Lymphoma such as non-Hodgkin's lymphoma, myeloma, plasma cell tumor, sudden myelogenous leukemia * Prolonged myeloid leukemia, adult T cell leukemia lymphomaLeukemia such as chronic lymphocytic leukemia, polycythemia vera, essential thrombocythemiaChronic myeloproliferative disease such as idiopathic myelofibrosis, lymphadenoma, pleural edema, ascites, etc. , Various types, adenomas, lipomas, fibromas, hemangiomas, fibroids, fibroids, endotheliomas and the like.

Regarding the food and drink of the present invention, the content of one or more selected from pentacyclic triterpenes and their physiologically acceptable salts or their derivatives depends on the frequency and intake of the food and drink Since it differs depending on other conditions, it may be adjusted as appropriate, and there is no particular limitation. For example, the adjustment can be made in the range of 0.001 to 80% by mass.

Since the food and drink of the present invention is in the form of food and drink, it can be easily and continuously taken, and suitable effects can be expected. Here, examples of the foods and drinks include various foods and drinks such as confectionery, processed foods, prepared oils and fats, processed oils and fats, dairy products, and drinks as described above, and the shape and properties are not particularly limited. , Semi-solid, gel, liquid, powder, etc. Since the pentacyclic triterpene and / or its specific derivative is generally fat-soluble, it can be said to be a particularly preferable form when the food or drink is a prepared oil or fat and / or a processed oil or fat. Although not particularly limited, for example, maslinic acid-rich formulated oils and the like are exemplified. Furthermore, foods and drinks obtained by using the prepared oil and fat and / or processed oil and fat as a raw material or as a fried or fried product are also preferable.

Further, as the food and drink of the present invention, an aqueous food and drink such as a drink, for example, a soft drink can also be obtained. In particular, some or all of the pentacyclic triterpenes may be It is preferable to use a salt and / or a specific derivative thereof, which is acceptable, because the pentacyclic triterpenes which generally exhibit lipophilicity can be improved in water solubility. Although not particularly limited, for example, water-based beverages such as soft drinks containing a physiologically acceptable salt or derivative of maslinic acid, which is inherently fat-soluble, may be mentioned. The present invention utilizes the above-mentioned effects, and provides a group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, beveric acid, beverin and a physiologically acceptable salt thereof, or a derivative thereof. It can be used as a food or drink for preventing tumor cell proliferation or a food or drink for preventing tumor cell metastasis, which contains a compound selected from the group consisting of: maslinic acid, erythrodiol, ursolic acid, baioru, and It can be used as a food or drink for treating tumors containing a compound selected from the group consisting of phosphoric acid, phosphorus and their physiologically acceptable salts, and derivatives thereof.

Pentacyclic triterpenes are a kind of triterpenes, and are pentacyclic compounds consisting of six isoprene units, which are basically composed of 30 carbon atoms, but undergo transfer, oxidation, and desorption during biosynthesis. Alternatively, it includes alkylated ones having different carbon numbers, and is generally classified by its skeleton. For example, oleanan triterpenes, ursan triterpenes, lupine triterpenes, hopane triterpenes, seratan triterpenes, friederane triterpenes, taraxeran triterpenes, taraxastan triterpenes, multifloran triterpenes And germicane triterpenes, which are naturally distributed widely in the plant kingdom.

The present inventors found that, among these, specific pentacyclic triterpenes, namely, masulinic acid of oleanan triterpene, erythrodiol, persolic acid of ursan triterpene, babol, and verpanic acid of lupine triterpene, and veperin Has excellent tumor cell growth inhibitory effect, tumor cell killing effect and tumor cell metastasis inhibitory effect It has been found that they have an antitumor effect, and that they can enjoy these effects when ingested in the form of food and drink, and completed the present invention. At the same time, pentacyclic triterpenes whose skeletons are similar to these: oleanolic acid of the oleanane triterpene, 1-amylin of the ursan triterpene, and ruyl of the lupine triterpene inhibit tumor cell growth. It has no antitumor effect such as no effect, tumor cell killing effect, tumor cell metastasis suppressing effect, etc., and found that it is ineffective when taken in the form of food and drink. That is, among the pentacyclic triterpenes, a specific substance has an antitumor effect in the present invention, and the structure is simply similar to the substance having an antitumor effect found in the present invention. Doing so alone has no antitumor effect. For example, oleanolic acid and maslinic acid have extremely similar structures, but their antitumor effects are incomparably different. In the present invention, they have found a substance having an antitumor effect that exists randomly.

The present invention relates to a compound selected from the group consisting of maslinic acid, erythrozol, ursolic acid, evanyl, berylic acid, berylin, and physiologically acceptable salts thereof, and derivatives thereof. The present invention relates to a food / drink for antitumor contained therein, preferably a food / drink for suppressing tumor cell proliferation, preferably a food / drink for killing tumor cells, and more preferably a food / drink for suppressing tumor cell metastasis.

Here, the physiologically acceptable salt is, in particular, a salt derived from a carboxyl group of a specific pentameric triterpene acid (partial structure: —COOX; X is any cationic substance), The present invention also includes those originally contained in the isolate from natural products in the present invention. In the present invention, there is no particular limitation so long as it is generally used in foods and drinks, and examples thereof include alkali metal salts such as sodium, potassium, and lithium, and alkaline earth metal salts such as calcium, magnesium, barium, and zinc. , Ammonia, methylamine, dimethylamine, trimethylamine, ethylamine, getylamine Alkylamine salts such as triethylamine, propylamine, butylamine, tetrabutylamine, pentylamine, hexylamine, ethanolamine, genoleamine, triethanolamine, propanolamine, dipropanolamine, isopropanolamine, diisopropanolamine. Salts such as alkanolamine salts such as luminamine, other organic amine salts such as piperazine and piperidine, and basic amino acid salts such as lysine, arginine, histidine and tributofan. Of these, alkali metal salts, alkylamine salts, alkanolamine salts and basic amino acid salts are preferred. In general, these salts are more soluble in water than the specific pentacyclic triterpenes from which they are derived, and are therefore particularly preferred in the present invention particularly when applied in an aqueous system.

The derivative is a derivative that can be formed biochemically or artificially. In the present invention, the derivative is not particularly limited as long as it is a possible derivative. For example, a derivative having an alcohol ester group, a fatty acid ester Derivatives having an alkoxy group, derivatives having an alkoxymethyl group, and glycosides. Of these, derivatives having an alcohol ester group, derivatives having a fatty acid ester group, derivatives having an alkoxy group, and derivatives having an alkoxymethyl group are particularly preferred in comparison with the specific pentacyclic triterpenes from which they are derived. In order to show lipophilicity, in the present invention, it is particularly preferable when applied in an oil system.Glycosides are more water-soluble than specific pentacyclic triterpenes from which they are derived, In the present invention, it is particularly preferable when applied in an aqueous system.

Some of these derivatives exist in nature and can be obtained by isolating them, or can be obtained by artificially forming them. In addition, the derivatives of the present invention can be derivatized again and their salts can be used.

In this way, maslinic acid, erythrodiol, persolic acid, vaoyl, verophosphoric acid, and veraline can be converted into appropriate physiologically acceptable salts and derivatives. Thus, the water-solubility or oil-solubility can be improved, and therefore, a product having improved handling properties-quality * anti-tumor effect can be set.

The alcohol ester group indicates a functional group formed as a result of a general dehydration reaction between a carboxyl group and an alcohol (partial structure: -COOR; R represents an arbitrary hydrocarbon-based functional group). That is, the derivative having an alcohol ester group of the pentacyclic triterpene in the present invention particularly refers to a derivative that can be formed from the carboxyl group and the alcohol. There are no particular restrictions on the alcohol at this time, but for example, methanol, ethanol, n-propanol, isopropanol, aryl alcohol, n-butanol, sec-butanol, tert-butanol, ethylene glycol, Trimethylsilyl alcohol, triethylsilyl alcohol, phenol, benzyl alcohol, saccharides and the like. Of these, derivatives formed from ethanol, triethylsilyl alcohol, methanol, n-propanol, isopropanol, and trimethylsilyl alcohol are preferred. The fatty acid ester group indicates a functional group formed as a result of a general dehydration reaction between a hydroxyl group and a fatty acid (partial structure: —OCOR; R represents any hydrocarbon-based functional group). That is, the derivative having a fatty acid ester group of the pentacyclic triterpene in the present invention particularly refers to a derivative which can be formed from the hydroxyl group and the fatty acid. There are no particular restrictions on the fatty acids at this time, but, for example, acetic acid, acetic anhydride, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, pivalic acid, caproic acid, caprylic acid, capric acid, pendecanoic acid , Lauric acid, myristic acid, palmitic acid, normitoleic acid, stearic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoleic acid, linolenic acid, arlinolenic acid, arachidic acid, arachidonic acid , Eicosapenic acid, diphenic acid, docosahexanoic acid, lignoceric acid, cerotic acid, montanic acid, melicic acid and the like. Among them, acetic acid, acetic anhydride, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, Palmitic acid, norremetic acid, stearic acid, oleic acid, elaidic acid, linoleic acid, linoleic acid, linolenic acid, alinolenic acid, arachidic acid, arachidonic acid, eicosapenic acid, behenic acid, docosahexaene Derivatives formed from acids are preferred.

The alkoxy group indicates a functional group formed as a result of a dehydration reaction between a general hydroxyl group and an alcohol (partial structure: —OR; R represents an arbitrary hydrocarbon-based functional group). That is, the derivative having an alkoxy group of the pentacyclic triterpene in the present invention particularly refers to a derivative which can be formed from the hydroxyl group and the alcohol. There are no particular restrictions on the alcohol at this time, for example, methanol, ethanol, n-propanol, isopropanol, aryl alcohol, n-butanol, sec-butanol, tert-butanol, ethylene glycol, Examples include trimethylsilyl alcohol, triethylsilyl alcohol, phenol, benzyl alcohol, and saccharides. Of these, derivatives formed from ethanol, triethylsilyl alcohol, methanol, n-propanol, isopropanol, and trimethylsilyl alcohol are preferred.

The alkoxymethyl group refers to a functional group formed as a result of a dehydration reaction between a general hydroxymethyl group and an alcohol (partial structure: one CH20R; R represents any hydrocarbon-based functional group) Indicate :). That is, the derivative of the pentacyclic triterbene having an alkoxymethyl group in the present invention particularly refers to a derivative that can be formed from the hydroxymethyl group and an alcohol. There are no particular restrictions on the alcohols used at this time, for example, methanol, ethanol, n-propanol, isopropanol, arylanolole, n-butanol, sec-butanol, tert-butanol. Examples thereof include ethanol, ethylene glycol, trimethylsilyl alcohol, triethylsilyl alcohol, phenol, benzyl alcohol, and saccharides. Of these, ethanol, triethylsilyl alcohol, methanol, n-propanoyl Derivatives formed from toluene, isopropanol and trimethylsilyl alcohol are preferred.

Glycosides in the present invention include, among the above derivatives having an alcohol ester group, derivatives having an alkoxy group, and derivatives having an alkoxymethyl group, in particular, carboxyl groups, hydroxyl groups, and hydroxy groups of pentacyclic triterpenes. A derivative that can be formed from a methyl group and a saccharide is shown (partial structure: —COOR, —OR, —CH 20 R; R represents any saccharide). There is no particular limitation on the saccharide at this time, and examples thereof include glucose, mannose, galactose, fructose, xylose, arabinose, fucose, rhamnose, glucosamine, galactosamine, glucuronic acid, and the like. Any body or any three body. These glycosides may be monosaccharides or oligosaccharides of various combinations of disaccharides or more. Some of these usually exist naturally and are known by the generic term saponin, but any of these may be used in the present invention.

The present invention relates to an antitumor food or drink containing maslinic acid, erythrodiol, persolic acid, baol, veric acid, veline, a physiologically acceptable salt thereof, or a derivative thereof. To be contained as an antitumor component means to contain to the extent that the desired antitumor effect, that is, the effect of suppressing tumor cell growth, the effect of killing tumor cells, and the effect of suppressing tumor cell metastasis can be obtained. In other words, the dosage of maslinic acid, erythrodiol, persolic acid, verbaol, berylic acid, veline and their physiologically acceptable salts, or their derivatives, contained in the food and drink of the present invention. Is the amount that is effective in preventing and / or treating tumors.o

About oleanan triterpene maslinic acid, erythrodiol, ursan triterpene ursolic acid, vaobal, lupine triterpene veritulinic acid, veprin and their physiologically acceptable salts, or derivatives thereof , The origin is not limited, and any of natural products, artificially synthesized products, commercially available products, and the like can be used.

Both maslinic acid and erythrodiol are one type of oleane-based triterpenes, and are substances already known to be present in various plants. When maslinic acid, erythrodiol, a physiologically acceptable salt thereof, and z or a derivative thereof are used in the food and drink of the present invention, the origin of these substances is not limited, and those obtained from nature Any of artificially synthesized and commercially available products can be used.

Maslinic acid (maslinic acid) is a kind of an oleane-based triterpene, and is a compound having a structure represented by chemical formula (1). It is known to have an anti-inflammatory effect and an anti-histamine effect. In nature, it is known to be present in olives, hops, knots, pomegranates, foliage, sage, jujube, and the like. In the food and drink of the present invention, the origin of maslinic acid and its physiologically acceptable salts or their derivatives is not limited, and any of those obtained from nature, artificially synthesized, commercially available products, etc. Although it can be used, for example, those obtained from natural sources such as olive, hops, hawaii, pomegranate, chickpea, sage, jujube, etc. are preferable. Plant and the like. Olive plants are preferred because they are cultivated stably and continuously and also contain maslinic acid and / or a physiologically acceptable salt thereof at a high concentration.

In the present specification, the term "olives" means an oriental plant and a product obtained in the Z or olive oil and Z or ore oil production process.

In the present invention, the physiologically acceptable salts and derivatives of maslinic acid are the same as described above. That is, the physiologically acceptable salts are those derived from —COOH in the chemical formula (1), and the types of the salts are not particularly limited as long as they are commonly used in foods and drinks or pharmaceutical compositions. There is no limitation. Specifically, for example, as the salt of maslinic acid, sodium masphosphate, potassium masphosphate, ammonium masphosphate, dimethylammonium masphosphate, calcium masphosphate, magnesium masphosphate and the like can be mentioned. Of these, sodium masphosphate and potassium masphosphate are preferred.

As a derivative of maslinic acid, for example, any one of the derivatives is derivatized, such as methyl maslinate, ethyl maslinate, n-propyl maslinate, isopropyl masinate, and n-butyl maslinate , Trimethylsilyl maslinate, triethylsilyl maslinate, mono-/?-D-glucoviranosyl ester, maslinic acid /?-D-galactoviranosyl ester, 3-0-acetyl monomaslinic acid, 3-0 — Propionyl-massic acid, 3-0—Butyllumassic acid, 3-0—Valeryl monomassic acid, 3-0—Caprylumuric acid, 3-0—Lauryl monomassic acid, 3—〇-1 Myristyl monomassic acid , 3-0—palmityl-maslinic acid, 3-0—palmi toreyl-mass Phosphoric acid, 3-0-stearyl monomassic acid, 3-0- stearoyl-massic acid, 3-0-oleum maslinic acid, 3-0-baxen Lumaric acid, 3-0-linoleyl monomassic acid, 3-0-linolenyl monomassic acid, 3-0-arachidyl-massic acid, 3-0-arachidonyl-massic acid ヽ 3-0-behylumaric acid, 2-0-Acetyl-maslinic acid, 2-0-Port mouth pionyl-maslinic acid, 2-0-butyryl-maslinic acid, 2-0-Valeryl-massic acid, 2-0-Capryl-massic acid, 2- 0-lauryl monomassic acid, 2-0-myristyl monomassic acid, 2-0-palmityl monomassic acid, 2-〇-noremi tolei lumas phosphoric acid, 2-0-stearyl monomassic acid, 2-0-o Rail monomassic acid, 2-0—Baxelum maslinic acid, 2-0—Linoleum maslinic acid, 2-0—Linolenyl monomassic acid, 2-0—Arachidyl monomassic acid, 2-0—Arachidonyl maslinic acid, 2 — 0 -Behenyl-massic acid, 3-methyl-massic acid, 3-0-ethyl-massic acid, 3-0- t-butyl-massic acid, 3-0-trimethylsilyl monomassic acid, 3-0- Triethylsilyl monomaslinic acid, 3-0-benzyl monomaslinic acid, 3-0— — D-glucovilanosyl monomaslinic acid, 3—one—D-galactopyranosyl monomaslinic acid, 3—

〇一? — D-glucuronopyranosyl-massic acid, 2-0-methyl monomassic acid

, 2-0-ethyl-maslinic acid, 2-0-t-butyl-maslinic acid, 2-0-trimethylsilyl-maslinic acid, 2—◦-triethylsilyl monomaslinic acid, 2-0-benzyl monomaslinic acid 2— 0 —? — D-glucoviranosyl monomaslinic acid, 2-0-? — D-galactobilanosyl-maslinic acid, 2-0-5—D-glucuronopyranosyl-maslinic acid, and the like. Ethyl masphosphate, triethylsilyl masphosphate, 3-0-acetyl-maslinic acid, 2-0-acetyl-maslinic acid, 2-◦-triethylsilyl-maslinic acid, 3-peacetearoyl-maslinic acid , 2-0-stearoyl-maslinic acid is preferred. In the above description, only one derivative is derivatized. However, it is needless to say that two or more of the derivatives whose positions and types can be derived are derivatized. No. For example, maslinic acid or 2,3-0-diacetyl, 2,3-0-ditriethylsilyl and 2,3-distearoyl of the above-mentioned preferable maslinic acid esters are preferable. In addition, only glycosides are listed as monosaccharides, but of course, disaccharides or more oligosaccharides selected from various saccharides may be used.

Erythrodiol (erythrodio 1) is a kind of oleanan-based triterpene and has a structure similar to that of chemical formula (2). Its action has been shown to be anti-inflammatory (Plant a. Med. VOL. 61, No. 2, 182-185 19 95) and the like. In nature, it is known to be present in olive, sunflower, calendula, gum arabic, kodokutan, nagaka konoki, and the like. In the food and drink of the present invention, the origin of erythrodiol or a derivative thereof is not limited, and any of those obtained from nature, artificially synthesized, commercially available products, and the like can be used. Those obtained from nature, such as sunflower, Kinsen, gum arabic, kodoxitan, and Nagakakonoki are preferred. Olives are particularly preferred, and specifically those obtained from the products obtained in the olive plant and Z or olive oil production process.

The physiologically acceptable salts and derivatives of erythrodiol are the same as described above.

Here, the derivative is not limited to the following, but, for example, any one of the derivatives is derived 3-0-Acetyl-erythrodiol, 3-0-peptidyl-pionyl-erythrodiol, 3-0-butyryl-erythrodiol, 3-0—Valeryl-erythrodiol, 3-0-capril —Erythrodiol, 3-0 —lauryl-erythrodiol, 3-0—myristyl-erythrodiol, 3-0—palmityl-erythrodiol, 3-0—palmitoreyl-erythrodiol, 3-0—stearyl-erythrodiol, 3-0-oleyl-erythrodiol, 3-0-baxenyl erythrodiol, 3-0-linoleyl-erythrodiol, 3-0-linolenyl erythrodiol, 3-0-arachidyl-erythrodiol, 3—0—arachidonyl—erythrodiol, 3 — 0—behenyl—erythrodiol, 28 — 0— Acetyl-erythrodiol, 28-0-propionyl-erythrodiol, 28-0-butyryl-erythrodiol, 28-〇-valeryl-erythrodiol, 28-8-0-capryl-erythrodiol, 28- 0—lauryl erythrodiol, 28—0—myristyl erythrodiol, 28—0—palmityl erythrodiol, 28—0—palmitoreyl erythrodiol, 28—0—stearyl erythro Trodiol, 28-0-oleyl-erythrodiol, 28-0-vaccenyl-erythrodiol, 28-0-0 linoleyl erythrodiol, 28-0-linolenyelerytrodiol, 28-0-arachidyl-erythrodiol , 28-0-arachidonyl-erythrodiol, 28-0-ぺ -phenyl-erythrodiol, 3-0-methyl ether Retrodiol, 3_0-ethyl-erythrodiol, 3-0-t-butyl-erythrodiol, 3-0-trimethylsilyl-erythrodiol, 3-0-triethylsilyl-erythrodiol, 3-0-pentylyl Erythrodiol, 28-0-methyl-erythrodiol, 28-0-ethyl-erythrodiol, 28-0-t-butyl-erythrodiol, 28-0-trimethylsilyl-erythritol, 28-8-0-triethylsilyl-ery Trodiol, 2 8-0 benzyl Retrodiol, 3—0 — /? —: D—Glucobiranosyl-erythrodiol, 3—0 — /? —— D—Galactobilanosyl-erythrodiol, 3—0 — /? — D—Glucuronoviranosyl-erythrodiol, 28 — 0 —? — D-glucoviranosyl erythrodiol, 28—0——D-galactobilanosyl-erythrodiol, 28-0——D-glucuronoviranosyl erythrodiol and the like. Of these, 3-0-acetyl-erythrodiol and 28-0-acetyl-erythrodiol are preferred. In the above, only one derivative is derivatized as a derivative, but of course, two or more derivatizable possible positions and types may be derivatized. For example, 3,28—◦—diacetyl-erythrodiol can be mentioned. Also, only glycosides are listed as the glycosides, but of course, disaccharides or more oligosaccharides selected from various saccharides may be used.

Ursolic acid and ebaol are both ursan triterpenes, and are known to be present in various plants. The physiologically acceptable salts and derivatives thereof are the same as described above. In the case of using ursolic acid, ebaol, a physiologically acceptable salt thereof, or a derivative thereof in the food or drink of the present invention, the origin of these substances is not limited. Any of natural, artificially synthesized and commercially available products can be used, but it is preferable to use natural products.

Ursolic acid, a kind of ursane triterpene, is a compound having the structure represented by chemical formula (3). It has anti-inflammatory, anti-atherosclerotic, anti-diabetic, and anti-hyperlipidemic effects (Jie Li u, Journal o τ Ethnopharmacol ogy, 49, 57-68, 1995). It is known. In nature, it is known to be widely distributed in fruits and leaves such as apples, cherries, and radish. In the food or drink of the present invention, persolic acid, a physiologically acceptable salt thereof, or a salt thereof The origin of the derivative is not limited, and any of those obtained from nature, artificially synthesized, commercially available products and the like can be used.For example, those obtained from natural sources such as apple, cherry, and walrus preferable.

Regarding ursolic acid, the physiologically acceptable salts and derivatives thereof are the same as described above.

Here, the physiologically acceptable salts are not limited to the following, but, for example, as salts of ursolic acid, sodium ursoluate, potassium ursorate, ammonium persulfate, dimethyl ursoluate Examples include ammonium, calcium ursolic acid, and magnesium ursolic acid.

As a derivative of persolic acid, for example, any one of which is derivatized may be methyl ursolic acid, methyl ethyl persole, η-propyl ursolic acid, isopropyl ursolic acid, isopropyl ursolic acid, Luic acid η-butyl ester, trimethylsilyl ursoluate, triethylsilyl ursoluate, uronic acid-/?-D-darcoviranosyl ester, ursolic acid mono-/-D-galacto Pyranosyl ester, 3-0-acetyl-ursolic acid, 3-0-propionyl-persolic acid, 3-0-butyryl-ursolic acid, 3-0-valeryl-ursolic acid, 3— 0-Capryluururonic acid, 3-0-Lauryl-ursolic acid, 3-0-Myristyl-persolic acid, 3-0-Palmityl-urso Le acid, 3-O-palmitic Toreiru - Urusoru acid, 3 1-0-Stearyl-l-uric-acid, 3-0-oleur-l-uric-acid, 3-0-Vaxen-l-ur-l-uric-acid, 3-0-Linole-l-ur-l-uric-acid, 3-0-Linol-l-urn-l-uric-acid Acid, 3-0—arachidyl ursolic acid, 3-0—arachid-2-perlsolic acid, 3-0—behenyl-ursolic acid, 3-0—methyl-ursolic acid, 3— 0-ethyl-ursolic acid, 3-0-t-butyl-ursolic acid, 3-0-trimethylsilyl-ursolic acid, 3-0-triethylsilyl-ursolic acid, 3-0-benzylic acid Ursolic acid, 3—0——D—Glucobiranosyl monoursolic acid, 3—0 —? — D—Galactopyranosyl monoursolic acid, 3—0—3—D—Glucuronovirano Siluric acid and the like. In the above, only one derivative is derivatized as a derivative, but it is needless to say that two or more derivatized possible positions and types of these derivatives may be derivatized. In addition, although only glycosides are mentioned as the glycosides, naturally, oligosaccharides of two or more disaccharides selected from various saccharides may be used.

Baobal (uvao l) is a kind of ursan triterpene and has a structure similar to the chemical formula (4). Its action has been anti-inflammatory (Plant a. Med. VOL. 61, No. 2) , 182-185 1995), glycerol phosphate dehydrogenase inhibitory activity (Japanese Patent Application No. 9-67249), etc. o Naturally, olive oils, oak urushi, sage, gum arabic, It is known to be present in プ upte etc. In the food and drink of the present invention, the origin of baioru or a derivative thereof is not limited, and any of those obtained from nature, artificially synthesized, and commercially available products can be used. Preferred are natural products such as olive oil, oak pork, sage, gum arabic and rypte. In particular, olive is preferable, and specifically, olive plants and those obtained from the products obtained in the oil or olive oil production process are preferable.

About Baool, its physiologically acceptable salts and derivatives are the same as above.

Here, the derivative is not limited to the following, but, for example, assuming that any one of the derivatives has been derivatized, 3-0-acetyl-baobaol, 3-0-propionyl-baobaol, 3 — 0—Ptyryl—Baobaol, 3—0—Valerylubaol—3, 0—Caprilubaol, 3—0—Laurilubaol, 3—0 One millistilled Baol, 3—0—Palmichl—Baol , 3-0-Palmitoreil-Baobal, 3-0-Stearyl-Baobaul, 3-0-Oreira-Baobaul, 3 _ 0-Baxen Lebaol, 3-0-Renoilebaobal, 3 — 0—Linolenyl-Baobaol, 3—0—Arachidyl-Baobaol, 3 —0—Arachidonil—Baobaol, 3-0—Benzyl-Baobaul, 28—0—Ba Cetyl-Baal, 28-◦—Propionyl -Baobaul, 28-0-Petiril-Baobaol, 28-0-Valerylubaol, 28-0-Power Prill-Baobaru, 28-◦Laurilubaol, 28 — 0—Myristyl-Baobaol, 28—0—Palmitil—Baobaol, 28—0—Palmi Toray Lebaul, 28—0—Stearyl—Baobaol, 28—0— Oleil-Baor, 28-0-Baxer-Baor, 28-0-Linoleur-Baor, 28-1-Linolenyl-Baor, 28-0-Arakidyl-Baor, 28 — 0 1-arachidonyl-baol, 2 8—0—between 2 baol, 3—0—meth Rubaol, 3_0—ethyl-baol, 3_0—t-butyl-baol, 3-0—trimethylsilyl—baol, 3-0—triethylsilyl—baol, 3-0—penzil—baol , 28-0-methyl-baol, 28-0-ethyl-baol, 28-0-t-butyl-baol, 28-0-trimethylsilyl-baol, 28-0-triethylsilyl-baobal, 28 —-Penzyl-l-baol, 3—0 _—— D—Darcovyranosyl—l-baol, 3—0 — /? — D—Galactopyranosyl—l-baol, 3—0 ——— D—Glucuronopyranosyl 100 baol, 28-0 —? — D-glucoviranosyl 10 baol, 28—0— 5—D—galactopyranosyl 10 baol, 28—0— — D—glucuronoviranosyl 10 bao And the like. Of these, 3-0-acetyl-baobal and 28_0-acetyl-baobal are preferred. In the above, only one derivative has been derivatized as an inducer. Of course, two or more of the derivatives whose positions and types can be derived may be derivatized. For example, 3, 28-0-diacetyl-baobaol. Also, only glycosides are listed as monosaccharides, but of course, disaccharides or more oligosaccharides selected from various saccharides may be used.

Bepulinic acid and bepulin are both lupine-based triterpenes and are known to be present in various plants. The physiologically acceptable salts and derivatives thereof are the same as described above. In the food and drink of the present invention, in the case of using phosphoric acid, veline, a physiologically acceptable salt thereof, or a derivative thereof, the origin of these substances is not limited and can be obtained from nature. Any of artificially synthesized and commercially available products can be used, but it is preferable to use natural products.

Betulic acid (be tul inic acid) is a kind of lupine triterpene and has a structure like chemical formula (5). Inflammatory action, Wound healing promoting action (Japanese Patent Publication No. 4-26632), alcohol absorption suppression action (JP-A-7-53385), hair growth-promoting action (JP-A-157-13) 9) etc. are known. In nature, it is known that it exists in a free state in sempuri, cinnamon, puddle peel, olives, and the like, and exists as a savonin in chixin ginseng, carrot, sugar beet, and the like. In the food and drink of the present invention, the origin of berylic acid, a physiologically acceptable salt thereof, or a derivative thereof is not limited, and can be obtained from natural sources, artificially synthesized, commercially available products, and the like. Any of them can be used, for example, sempuri, cinnamon, puddle, olive, chixin ginseng

And those obtained from nature such as carrot and sugar beet. In particular,

And those obtained from the product obtained in the production process of oil oil and / or oil.

(4) Regarding phosphoric acid, physiologically acceptable salts and derivatives thereof are the same as described above.

Here, physiologically acceptable salts are not limited to the following, but include, for example, sodium phosphate, potassium phosphate, ammonium phosphate, dimethylammonium phosphate, calcium phosphate, and phosphate phosphate. Examples include magnesium. Of these, sodium perphosphate and potassium perphosphate are preferred. Derivatives of verpulinic acid include, for example, those in which any one of the derivatives is derivatized, such as methyl verpoleate, ethyl berylate, n-Propyl ester, isopropyl vertate, n-butyl vertate, trimethylsilyl vertate, triethylsilyl pertate, monophosphate /?-: D-glucoviranosyl ester, monophosphate /? — D-galactobilanosyl ester, 3-0-acetyl-perperic acid, 3—1-propionyl-ruberic acid, 3-0—butyryl-perperic acid, 3-0—valeryl monoperin Acid, 3-0-capryl-berpulinic acid, 3-0 _lauryl-monoberic acid, 3-0-myristyl-berpulinic acid, 3〇-palmityl-berpulinic acid, 3-0 -palmi-toreyluberin Acid, 3-0-stearyl-peracid, 3-0-oleuveric acid, 3-0-baxenerubereveric acid, 3-0-linoleyl monobernic acid, 3-0-linoleni -Beperic acid, 3-0-Arachidylruberic acid, 3-0-Arachidonyl-beperic acid, 3-0-Beheruveric acid, 3-0-Methyl-bellinic acid, 3—◦— Ethyl monophosphate, 3-0-t-butyl-beta acid, 3-0-trimethylsilyl monophosphate, 3-0-triethylsilyl-phosphate, 3_0_benzyl monophosphate, 3 — 0— /? — D-Darcopyranosyl monobernic acid, 3—0 — /? — D-Galactobilanosyl-berpulinic acid, 3 —0— — No. Of these, ethyl berylate is preferred. In the above description, only one derivative has been derivatized. However, it is needless to say that two or more derivatizable positions and types of these derivatives may be derivatized. In addition, only glycosides are listed as monosaccharides, but of course, disaccharides or more oligosaccharides selected from various saccharides may be used.

Betuline (betu 1 in) is a kind of lupine triterpene and has a structure similar to the chemical formula (6). Its action has so far been an inhibitory action on bioprotein denaturation (Japanese Patent Application Laid-Open No. Hei 9-67253). Glycerophosphate dehydrogenase inhibitory action (Japanese Patent Application Laid-Open No. Hei 9-167249), lipase inhibitory action (Japanese Patent Application Laid-Open No. 10-2653228), liver disease preventive action ( Japanese Patent Application Laid-Open No. 11-209925) is known. In nature, it is known to be present in birch bark and the like. In the food and drink of the present invention of the present invention, the origin of beverin or a derivative thereof is not limited, and any of those obtained from nature, artificially synthesized, and commercially available products can be used. For example, those obtained from nature such as birch bark are preferred.

The physiologically acceptable salts and derivatives of beverin are the same as described above.

Here, the derivative is not limited to the following, but, for example, assuming that any one of the derivatives is inducted, 3-0-acetyl-verulin, 3--1-propionyl-Lupperin, 3-0-butyryl-one Perrin, 3—◦_valeryl monolin, 3—0—force prill, 3-0—lauryl monoberin, 3-0—myristyl—velin, 3-0—palmityl monoberin, 3— 0—Palmi Toray Luberin, 3—0—Stearyl monoberin, 3—0—Oreylberin, 3—0—Baxenium Luberin, 3—0—Linoleurin Berlin, 3—0—Linolenyl-berin , 3-0—Arachidylruberin, 3-0—Arachidonylruberin, 3-0—Bevel2, 28-0—Acetylruberin, 28—0—Propioniruberin, 2 8—0—all butyryl Phosphorus, 2 8—0—Valeryl Belin, 2 8—Hydroxypril—Berlin, 28—0—Lauryl—Berlin, 28—0—Myristyl—Berlin, 28—0—Palmicillin Berin, 2 8—0—No Lumi Toleuperin, 28-0-stearyl monoperiline, 28-0-0 Oreperuperin, 28-0-0 Baxe-Lupeline, 28-8-0-Linoreuperin, 28-0 —Linolenyl-berin, 2 8—0—Arachidyl-ruberin, 28—0—Arachidonyl-berin, 28—0—Bevel, 2-ruberin, 3—0—Methyl-perin, 3—0—Ethyl-berin, 3-0-t-butyl-verin, 3-0-trimethylsilyl monolin, 3-0-triethylsilylperin, 3-0-benzyl monoperin, 28-0-methyl-verin, 28 — 0—etiruberin, 28—0—t—butyl monophosphate, 28—0—trimethylsilyl—bellin, 28—0—triethylsilyl monoberin, 28—0—penzylperperin , 3— 0—? — D—Darcovyranosyl perveline, 3 — 0-? — D—galactovyranosyl-belin, 3— 0— /? — D—glucuronopyranosyl-belin, 28—0— — D—glucovilanosyl-belin, 28—0— 5—D —Galactoviranosyl 1-verin, 28—0——D—Glucuronopyranosyl--1 verin and the like. Of these, 3-0-acetyl-perrin and 28-0-acetyl-perrin are preferred. In the above, only one derivative is derivatized as a derivative, but of course, two or more derivatizable possible positions and types may be derivatized. For example, 3,28-0-diacetyl-berin is preferable. In addition, only glycosides are listed as monosaccharides, but naturally, disaccharides or more oligosaccharides selected from various saccharides may be used.

These pentacyclic triterpenes are naturally extracted from the plants described above, specifically, extracted with water and / or an organic solvent, and further concentrated and / or fractionated and purified. It can be obtained by processing. In other words, each plant can be extracted with water and / or an organic solvent, and the extract is then subjected to solvent extraction, a method that utilizes the difference in solubility with impurities, fractionated precipitation, recrystallization, ion-exchange resin. Method, liquid chromatography, etc., alone or in combination as appropriate. Alternatively, it can be separated and purified by repeated use.

In particular, maslinic acid and / or its physiologically acceptable salts can be extracted from olive plants with water and / or an organic solvent, and the extract is subjected to a solvent extraction method to determine the solubility difference with impurities. Separation and purification can be performed by using a method, a fractional precipitation method, a recrystallization method, an ion exchange resin method, a liquid chromatography method, or the like alone or in an appropriate combination, or by repeatedly using the method.

Olive plants (Ole ae eur rop ae a L.) can be used regardless of the place of origin such as domestic or European, edible or oiled. The maslinic acid and / or its physiologically acceptable salt contained in the food and drink of the present invention can be obtained mainly from fruits or seeds of natural plants, orip plants. , Leaves, stems and buds. In addition, it can be suitably obtained from these dried, pulverized, and degreased products. Of these, defatted fruits (including pericarp), dried pericarp, and crushed pericarp are preferred. In addition, products generated during the production of olive oil, such as pressed residue, extracted residue, squeezed residue, pressed oil, extracted oil, degummed soap, deacidified soap, dark oil, waste decolorizer , Can be obtained from deodorized scum, oiled juice, wastewater, waste filter media. Of these, oil residue is preferred.

In addition, when water is added to the above-mentioned olive plant fruits and their defatted products, for example, by adding water, or when humidification treatment such as steaming is performed, these olive plant fruits and their defatted products swell appropriately. Therefore, the extraction efficiency is improved, which is preferable. In particular, maslinic acid and / or a physiologically acceptable salt thereof is present at a high concentration in the defatted product of an olive plant, and the obtained maslinic acid and / or a physiologically acceptable salt thereof are contained. This is preferable because it is not necessary to remove oil from the oil.

The defatted product can be used as a raw material from an oil residue obtained during the oil refining process or an extraction residue obtained using hexane or the like.

In addition, lipid components contained in olive plants or the defatted product are Extraction and removal with one or more known non-water-soluble organic solvents such as hydrocarbons such as acetylene, heptane, etc., lower fatty acid alkyl esters such as ethyl acetate, and getyl ether. The defatted material obtained by repeating the treatment can also be suitably used. By extracting the olive plant from the above olive plant with water and / or an organic solvent, maslinic acid and / or a physiologically acceptable salt thereof contained in the food and drink of the present invention can be obtained. Can be obtained.

The organic solvent used to obtain maslinic acid and / or a physiologically acceptable salt thereof from the olive plant may be either a hydrophilic organic solvent or a hydrophobic organic solvent. Specifically, as a hydrophilic organic solvent, methyl alcohol, ethyl alcohol, glycerin, propylene glycol, alcohol such as 1,3-butylene glycol, acetone, tetrahydrofuran, acetonitrile, 1,4-dioxane, pyridine, dimethyl sulfoxide , N, N-dimethylformamide, acetic acid, and other known organic solvents. Examples of hydrophobic organic solvents include hexane, cyclohexane, carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloroethane. And known organic solvents such as ethyl ether, ethyl acetate, benzene, and toluene. These organic solvents can be used alone or in combination of two or more.

Industrially, it is preferable to use a hydrophilic organic solvent from the viewpoint of, for example, permeability to plant tissue, extraction efficiency, and the like, and it is preferable to use a hydrated hydrophilic organic solvent. Specific examples include alcohols such as methyl alcohol, ethyl alcohol, glycerin, propylene glycol and 1,3-butylene glycol, organic solvents such as acetone, tetrahydrofuran, and acetonitrile, and water-containing solvents thereof. The maslinic acid and / or a physiologically acceptable salt thereof contained in the food or drink of the present invention is obtained from an orient plant by one or more kinds selected from these. be able to.

The extraction conditions are not particularly limited. For example, the temperature may be 5 ° C to 95 ° C; preferably 10 ° C; to 90 ° C, more preferably 15 ° C; to 85 ° C. It can be suitably extracted at room temperature. Higher temperatures tend to increase extraction efficiency. The pressure can be suitably extracted at normal pressure, under pressure, or under reduced pressure by suction or the like. Further, in order to improve the extraction efficiency, the extraction can be carried out by shaking extraction or an extractor equipped with a stirrer. The extraction time is several minutes to several hours, depending on other extraction conditions. The longer the time, the more sufficient extraction is performed. However, the extraction time may be appropriately determined according to production conditions such as production equipment and yield.

In addition, the solvent used in the extraction is 1% of the raw material, regardless of whether water is used alone, organic solvent is used alone, or water and organic solvent are mixed. Up to 100 times (“mass / mass”; the same applies hereinafter), preferably 1 to 20 times.

Further, in consideration of the safety to the human body and the like, it is particularly preferable to extract with water, a water-containing lower alcohol, or an anhydrous lower alcohol.

Furthermore, taking into account the yield of the obtained maslinic acid and / or its physiologically acceptable salt and the strength of the antitumor effect, the hydrated lower alcohol having a lower alcohol content of 10% by mass or more is considered. It is preferred to extract with Further, it is preferable to use a water-containing alcohol having a lower alcohol content of 10% by mass to 95% by mass, and most preferably a water-containing lower alcohol having a lower alcohol content adjusted to 30% by mass to 95% by mass. Alcohols are preferred.

Here, the alcohol used in the present invention is a primary alcohol such as methyl alcohol, ethyl alcohol, 1-propanol, 1-butanol, a secondary alcohol such as 2-propanol ヽ 2-butanol, Tertiary alcohols such as 2-methyl-2-propanol, ethylene glycol, propylene glycol, 1,3-butylene Known solvents, such as liquid polyhydric alcohols such as glycol, can be used, and these solvents can be used alone or in combination of two or more.

The lower alcohol is a known alcohol having 1 to 4 carbon atoms, for example, the aforementioned primary, secondary, tertiary, or liquid polyhydric alcohols, etc., and one or more of these are combined. Can be used.

By removing the solvent and water from the crude extract and / or crude extract thus obtained, maslinic acid and / or a physiologically acceptable salt thereof in the present invention can be obtained.

The removal of the solvent and water can be performed by a known method such as distillation under reduced pressure, reduced pressure / vacuum drying, freeze drying, spray drying and the like.

Of course, the solvent or water may be contained, and the state is not particularly limited.

The extract from the defatted product is preferable because it does not contain fat-soluble components such as triglyceride sterol and tocoprole, and it is not necessary to remove and purify these components. In addition, defatted matter is a very effective method of using orifices, because it can use pressed and extracted cakes obtained by squeezing olive oil because it contains residue after oiling. Since waste or feed is used, it is an excellent method in terms of production cost.

Further, in order to further enhance the antitumor effect of maslinic acid and / or its physiologically acceptable salt extracted from the olive plant, maslinic acid contained in the food and drink of the present invention and / or physiology of maslinic acid and / or physiology It is preferable to carry out a concentration treatment or the like of a salt that is acceptable in practice.

The concentration conditions are not particularly limited, and examples thereof include a method using solubility in water. Maslinic acid and Z or a physiologically acceptable salt thereof contained in the food and drink of the present invention are relatively low in polarity and poorly water-soluble compounds. Utilizing this property, the crude extract from the olive plant can be dissolved in water-insoluble components and / or water. Separation into components that do not dissolve, that is, components that are poorly water-soluble, and components that are easily soluble in water, enables significant concentration. The poorly water-soluble and other components contained in the crude extract from Olive plants are significantly superior to the whole crude extract from Olive plants in their antitumor effect. It can be confirmed that the acceptable salts are concentrated.

Components having poor water solubility can be easily obtained by adding a crude extract from an olive plant to water, stirring and collecting a precipitated portion by filtration or the like. In addition, maslinic acid and / or its physiologically acceptable salt contained in the food and drink of the present invention can be concentrated by one-liquid distribution using a combination of common solvents, if necessary. it can. The combination of solvents is generally difficult to define, but for example, a combination of water and a hydrophobic organic solvent can be mentioned.

And known organic solvents such as carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloroethane, dimethyl ether, ethyl acetate, n-butanol, benzene and toluene. Of these, hexane, ethyl acetate, and n-butanol are preferred.

Since maslinic acid and / or its physiologically acceptable salt are poorly water-soluble, unnecessary water-soluble components can be removed by separating the hydrophobic organic solvent phase. By removing the solvent, maslinic acid and / or a physiologically acceptable salt thereof can be easily concentrated.

Further, maslinic acid and / or a physiologically acceptable salt thereof contained in the food and drink of the present invention is preferably subjected to fractionation and purification from the above-mentioned extract and / or concentrate. As a result, the concentration can be more than the above concentration, and the target component can be isolated.

The advantages of the fractionation / purification treatment include not only that the antitumor effect and the like can be greatly improved, but also that impurities can be removed. You That is, when the fractionation and purification are performed, maslinic acid and / or a physiologically acceptable salt thereof can be obtained as white crystals, and thus the food and drink of the present invention is suitable without adding an extra color. It is advantageous because it has the merit that it can be blended into a mixture. The method of fractionation / purification is difficult to specify in general, but examples include recrystallization method, fractional precipitation method, and method using chromatography. In particular, among the chromatographic methods, the method utilizing liquid chromatography is effective in fractionating maslinic acid and / or a physiologically acceptable salt thereof contained in the food and drink of the present invention in good yield. It is preferable because it can be purified. Specific examples of liquid chromatography include normal-phase liquid chromatography, reverse-phase liquid chromatography, thin-layer chromatography, paper chromatography, high-performance liquid chromatography (HPLC), and the like. When fractionating and purifying maslinic acid and / or a physiologically acceptable salt thereof contained in food and drink, any method can be used. In particular, normal phase liquid chromatography, reverse phase liquid chromatography, and high performance liquid chromatography (HPLC) are preferable in consideration of the separation ability, the throughput, the number of steps, and the like.

Here, normal phase liquid chromatography refers to, for example, the following method. That is, for example, a column was prepared using silica gel as the stationary phase, a mixture of hexane-monoethyl acetate, and a mixture of chloroform and methanol in a mobile phase, and the crude extract from the olive plant or its concentrate was used as the load factor. 0.1 to 5% (wt (mass) Zv (volume)), and elute a given fraction by continuous elution with a single mobile phase or stepwise elution with increasing solvent polarity. is there.

Reverse phase liquid chromatography refers to, for example, the following method. That is, for example, silica (ODS) to which octadecylsilane is bonded is used as a stationary phase, a water-methanol mixture, a water-acetonitrile mixture, a water-acetone mixture or the like as a mobile phase, and a column is prepared from crude plants. Load the extract or its concentrate from 0.1 to 0.1 5% (wt (mass) / v (volume)), and elute the desired fractions by continuous elution with a single solvent or stepwise elution with successively decreasing solvent polarity. You.

High-performance liquid chromatography (HPLC) is, in principle, the same as normal-phase liquid chromatography or reverse-phase liquid chromatography described above, and enables faster and higher-resolution fractionation and purification. To do.

By combining one or more of the above methods, maslinic acid and / or its physiologically acceptable salt can be very concentrated and can be obtained in a state where impurities have been removed.

Furthermore, by combining one or more of the above methods, the purity of maslinic acid and / or its physiologically acceptable salt can be adjusted, and the strength of the antitumor effect as required, Characteristics and the like can also be designed. That is, the antitumor effect can be designed by appropriately adjusting the strength and the mechanism of action of the antitumor effect. The strength of the antitumor effect can be adjusted by, for example, concentrating when a stronger effect is required, and diluting when a weaker effect is sufficient. Alternatively, the strength of the antitumor effect can also be adjusted by combining maslinic acid and the like with other antitumor foods and drinks other than maslinic acid and the like targeted in the present invention. The mechanism of action of the antitumor effect includes suppression of tumor cell growth, tumor cell death and suppression of tumor cell metastasis. Such action can be adjusted by combining other antitumor foods and drinks other than the present invention with maslinic acid and the like.

Regarding the above-mentioned concentration treatment, the concentration treatment can be preferably repeated, and different concentration treatments can be combined. Similarly, regarding the fractionation / purification treatment, preferably, the fractionation / purification treatment can be preferably repeated, and further, different fractionation / purification treatments can be combined. Furthermore, fractionation and purification may be performed after concentration, and fractionation and purification may be performed after fractionation and purification. After the concentration treatment, a fractionation / purification treatment can be performed, and the concentration treatment can be further performed. Of course, a combination other than the above-mentioned combination may be used.

By variously combining the above-described extraction treatment, concentration treatment, fractionation and / or purification treatment, maslinic acid and / or a physiologically acceptable salt thereof can be suitably obtained. The combination is not particularly limited, but specific examples of the series of processing include the following methods.

For example, after extracting an olive plant with water and / or a hydrophilic organic solvent, a part or all of the hydrophilic organic solvent is removed from the obtained extract, and if necessary, water is added and the mixture is stirred. The water-insoluble content precipitated in the solution is concentrated. Precipitated water-insoluble components can be recovered by filtration, centrifugation or the like.To improve the recovery efficiency, the aqueous solution can be subjected to treatment such as addition of water and stirring if necessary. . In addition, the extract in the dry state from which water and / or the hydrophilic organic solvent has been removed from the extract obtained from the olive plant is subjected to the treatment such as addition and stirring of water in the same manner as described above, and the water is insoluble by filtration or the like. Concentration processing can be performed by collecting the components. According to this concentration method, since the treatment is performed in an aqueous system, it is superior in safety to concentration using a solvent, and the range of equipment that can be used is wide. In addition, since it contains almost no oil, it is also excellent in concentration and purification efficiency, so these concentrates are preferably fractionated and purified by normal-phase and / or reverse-phase chromatography and Z or recrystallization. By doing so, highly purified maslinic acid and / or a physiologically acceptable salt thereof can be suitably obtained.

In addition, the hydrophilic organic solvent is removed from the extract obtained from the olive plant, water is added to the remaining aqueous solution as needed, and a hydrophobic organic solvent is further added, whereby water-hydrophobic organic solvent is added. Concentration can be performed by liquid-liquid distribution with a solvent. In addition, water is added to the dried extract in the same manner as described above, and the hydrophobic organic solvent is added. By adding a medium, concentration treatment can be performed by liquid-liquid partitioning with a water-hydrophobic organic solvent. By fractionating and purifying these concentrates by normal and / or reverse phase chromatography and / or recrystallization, highly purified maslinic acid and / or its physiologically acceptable Salt can be obtained.

Here, the amount of water to be added at the time of liquid-liquid distribution is not particularly limited as long as an amount capable of distributing is used, but the amount is preferably 1 to 100 times, more preferably 1 to 100 times the mass of the dried extract. Is about 5 to 50 times, more preferably about 10 to 30 times.

Further, in the liquid-liquid partitioning with water-hydrophobic organic solvent, the water and the hydrophobic organic solvent are preferably used in a ratio of water: hydrophobic organic solvent = 9: 1 to 1: 9 (volume ratio), It is more preferable to use 8: 2 to 2: 8.

Also, maslinic acid in a mixture of maslinic acid obtained from the product obtained in the olive plant and / or olive oil production process and a physiologically acceptable salt thereof and a physiologically acceptable maslinic acid. The total content of those salts is preferably 95% or more, more preferably 95% to 99.99%. The content can be measured by, for example, gas chromatography.

Although the food and drink of the present invention contains maslinic acid and phosphorus or a physiologically acceptable salt thereof, the food and drink of the present invention can also be obtained by containing the extract and concentrate. In addition, by adjusting the degree of concentration, purification, etc., the concentration of maslinic acid and Z or a physiologically acceptable salt thereof can be adjusted. Can be. In other words, when a stronger effect is required, the composition can be concentrated, and when a weaker effect is sufficient, a diluted composition can be used, so that a form suitable for use at a concentration according to the purpose of use can be obtained.

Since olive oil contains maslinic acid and the like, it is preferable to further use olive oil as an oily component in the food and drink of the present invention since a more favorable antitumor effect and the like can be obtained.

Also, maslinic acid and / or a physiologically acceptable salt thereof can be obtained from an olive plant. When oleanolic acid is extracted, oleanolic acid and / or a physiologically acceptable salt thereof is extracted at the same time, and this oleanolic acid and / or a physiologically acceptable salt thereof has an inhibitory activity against carcinogenesis. In addition, because of its excellent compatibility with maslinic acid, these mixtures can be directly blended with the food and drink of the present invention. In addition, maslinic acid and / or a physiologically acceptable salt thereof are also preferable since a synergistic effect can be expected in the present invention. When maslinic acid and / or its physiologically acceptable salts are extracted, separated and purified, etc. from the oriental plant, oleanolic acid and / or its physiologically acceptable salts are adjusted by adjusting the conditions. Maslinic acid and / or a physiologically acceptable salt thereof, oleanolic acid and / or a physiologically acceptable salt thereof can be isolated separately from Olive plants, and It can also be obtained by mixing. Further, a mixture of maslinic acid and / or a physiologically acceptable salt thereof obtained from different raw materials and oleanolic acid and / or a physiologically acceptable salt thereof may be used.

The pentaphosphates other than the maslinic acid and / or the physiologically acceptable salt thereof which are the object of the present invention are also the raw materials and methods described for maslinic acid and / or the physiologically acceptable salt thereof. It can be isolated from natural products according to

It is preferable to use an isolated product from a natural product as a food or drink because the effects of impurities derived from the natural product are eliminated and the colorless to pale color and / or odorless to almost odorless state is obtained. Therefore, by isolating, from natural products, the specific pentagonal triterpenes and physiologically acceptable salts thereof, or derivatives thereof, which are the object of the present invention, the isolation of the tertiary triterpenes may affect the flavor and the like of the dishes to be served. You can cook without. In particular, it can be blended in dishes that do not require the flavor of natural products used as raw materials such as olive oil. Therefore, the foods and drinks of the present invention include foods and drinks that can be cooked or blended without being affected by the type of natural product used as a raw material. Furthermore, when olive or olive oil is ingested as it is, only a small amount of the pentacyclic triterpenes targeted by the present invention can be ingested, but pentacyclic triterpenes isolated from natural products are blended. By ingesting food or drink, a large amount of the specific pentacyclic triterpenes targeted by the present invention can be relatively easily ingested.

In addition, pentacyclic triterpenes contained in orifices and the like are generally fat-soluble substances, so they are often present in fats and oils. Therefore, it is difficult to mix them in water-based foods and drinks. However, pentagonal triterpenes isolated from natural products can be incorporated into oil-based foods and water-based foods and drinks. By preparing an aqueous food or drink such as a soft drink, it is possible to easily ingest, for example, several g to several 10 g of the pentacyclic triterpenes targeted in the present invention.

Furthermore, the foods and drinks of the present invention containing specific pentacyclic triterpenes isolated from natural products are preferable because impurities or contaminants that inhibit absorption into the body of the present invention are removed. It is preferable because the effects of the present invention, that is, the antitumor effect, the effect of suppressing tumor cell growth, the effect of killing tumor cells, and the effect of suppressing tumor cell metastasis can be obtained.

Although maslinic acid, erythrodiol, persolic acid, baol, verpulinic acid, berlin and their physiologically acceptable salts or their derivatives contained in the food and drink of the present invention have an antitumor effect, Its effects include a tumor cell growth inhibitory effect, a tumor cell killing effect, and a tumor cell metastasis inhibitory effect.

Tumor cell growth inhibitory effect is intended to prevent tumor cells that have already developed in the body, especially cancer cells, from proliferating further and affecting the living body. A low intake can make a significant contribution prophylactically, that is, in suppressing the progress of cancer at invisible levels.

Tumor cell killing effect is intended to prevent tumor cells that have already developed in the body, especially cancer cells, from performing cell activities. Significant contribution to killing cancer cells that have developed at invisible levels Can be given.

The effect of inhibiting tumor cell metastasis is that tumor cells, especially cancer cells, that have developed in the body, die while they are on the bloodstream, in the process of arriving and proliferating to other parts of the bloodstream. It is intended to suppress or kill proliferation as soon as it arrives at another site, and daily intake can greatly contribute to preventing or suppressing metastasis of cancer cells at an invisible level. it can.

The tumor cell growth inhibitory effect and tumor cell killing effect are shown by the following method using B-16 melanoma cells.

A 6-well plate was inoculated with a predetermined amount of B-16 melanoma cells, incubated at 37 ° C; 5% carbon dioxide, and cultured on the next day and on the 5th day of culture. Acid, erythrodiol, ursolic acid, ebaol, veric acid, verin, and their physiologically acceptable salts, or derivatives thereof). On the day, the number of surviving cells is counted, and the cell proliferation rate is determined from this, and the tumor cell growth inhibitory effect and tumor cell killing effect are evaluated. Compare with the cell growth rate without the sample (control).

In the case of maslinic acid, erythrodiol, ursolic acid, evanol, benzoic acid, vedulin and their physiologically acceptable salts, or their derivatives, even at very low concentrations, they can be added in a concentration-dependent manner. Inhibits the growth of B-16 melanoma cells or kills B-16 melanoma cells. That is, maslinic acid, erythrodiol, ursolic acid, ebaol, vericulic acid, verulin and their physiologically acceptable salts, or derivatives thereof, have a very potent tumor cell growth inhibitory effect. It has a tumor cell killing effect. Oleanolic acid, which is known as an overnight inhibitor of carcinogenesis promoter, does not suppress the growth of B-16 melanoma cells at all, but maslinic acid, erythrodiol, persolic acid, ゥ baol, and veline in the present invention. Acids, betaline and their physiologically acceptable salts, or their derivatives, It has an excellent tumor cell growth inhibitory effect and tumor cell killing effect.

In addition, since the effect is exhibited even at a low concentration, a relatively small amount of the agent is required to exhibit the expected tumor cell growth inhibitory effect and tumor cell killing effect. Can be expected. In addition, since it is effective in a concentration-dependent manner, it is possible to meet the purpose of use and the required effect by increasing or decreasing the amount of addition.

The evaluation of the tumor cell metastasis inhibitory effect can be performed by a malignant melanoma metastasis inhibitory test or the like. That is, a suspension of B16 melanoma cells prepared in advance was injected intravenously into C57BL16 female mice, and a sample of a predetermined concentration was dissolved every other day from the second day after injection. Cottonseed oil is administered intraperitoneally by injection or orally using a probe. The control group receives only cottonseed oil. On the 15th day after the injection of B16 melanoma cells, the lungs are removed and the number of metastatic cancer foci that have metastasized to the lungs is counted, and the metastasis suppression rate is calculated. From this metastasis suppression rate, the tumor cell metastasis suppression effect is evaluated.

In this evaluation, administration of oleanolic acid, which is known as a carcinogenesis promoter inhibitor, has no significant difference from the control (non-administration) group and has no effect of suppressing tumor cell metastasis, but maslinic acid, erythrodiol, and persol There is a significant difference between the control (non-administration) group and the administration of the acid, ebaol, diphosphate, veline and their physiologically acceptable salts, or their derivatives. Suppress metastasis of melanoma. In other words, maslinic acid, erythrodiol, persolic acid, ebaol, veric acid, verin, and their physiologically acceptable salts, or derivatives thereof, have a very strong inhibitory effect on tumor cell metastasis. .

Since the effect is exhibited even with a relatively small dose, the amount of addition for exhibiting the expected effect of suppressing tumor cell metastasis is small, and an effect in a high safety range can be expected. Also, since it is effective in a concentration-dependent manner, the purpose Or the effect you need.

The present invention contains a compound selected from maslinic acid, erythrodiol, ursolic acid, vaoyl, veriphosphoric acid, pelin, and a physiologically acceptable salt thereof, or a derivative thereof. Related to antitumor food and drink. To contain as an antitumor component means to contain an antitumor effect such as a tumor cell growth inhibitory effect, a tumor cell killing effect, a tumor cell metastasis inhibitory effect, etc., and to produce an antitumor effect. That is to expect and mix.

In the food and drink of the present invention, the content of maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, berylin, and their physiologically acceptable salts, or derivatives thereof is particularly limited. It can be adjusted as appropriate depending on the type of pentacyclic triterpenes contained, the type of food and drink, the amount of intake, the frequency of intake, the weight of the ingesting person, the sex, etc., and is not particularly limited, but is, for example, 0.0001 to 80 % By mass, preferably from 0.001 to 50% by mass, more preferably from 0.01 to 30% by mass, particularly preferably from 0.1 to 15% by mass, most preferably from 0.1 to 10% by mass. In particular, as a preventive food or drink mainly having a tumor cell growth inhibitory effect or a metastasis inhibitory effect, for example, 0.0001 to 30% by mass, more preferably 0.001 to 20% by mass, and still more preferably 0.1 to 20% by mass. 01 to 15% by mass, more preferably 0.01 to 15% by mass, further preferably 0.1 to 15% by mass, still more preferably 0.5 to 15% by mass, and most preferably 1 to 10% by mass. In addition, foods and drinks for treatment mainly due to the effect of killing tumor cells include, for example, 0.001 to 80% by mass, preferably 0.01 to 50% by mass, more preferably 0.1 to 30% by mass, It is more preferably from 0.1 to 20% by mass, still more preferably from 0.5 to 15% by mass, and most preferably from 1 to 15% by mass.

The content of maslinic acid and / or a physiologically acceptable salt thereof is not particularly limited, but is, for example, 0.0001 to 80% by mass, preferably 0.000% by mass. 1 to 50% by mass, more preferably 0.01 to 30% by mass, further preferably 0.1 to 20% by mass, still more preferably 0.5 to 15% by mass, and most preferably 1 to 50% by mass. It is 15% by mass.

The pentagonal triterpenes and derivatives having an alcohol ester group, derivatives having a fatty acid ester group, derivatives having an alkoxy group, and derivatives having an alkoxymethyl group in the present invention are generally fat-soluble, and are therefore oil-based. Or it can be suitably blended with emulsified foods and drinks. In particular, when ingested as fats and oils or processed fats and oils, they are expected to be absorbed together with the oil, and are therefore preferable in terms of absorbability.

In addition, the physiologically acceptable salts or glycosides of the pentacyclic triterpenes in the present invention generally show water solubility, so that they are uniformly dissolved or dispersed in aqueous or emulsified food or drink. Thereby, it can be suitably blended. In particular, beverages and the like are often commercialized in aqueous or emulsified systems. In this case, if necessary, pentacyclic triterpenes can be suitably converted to physiologically acceptable salts or glycosides thereof. Can be blended.

Naturally, by increasing the amount of the pentacyclic triterpenes and their physiologically acceptable salts or their derivatives in the present invention, the production of foods and drinks having more excellent antitumor effects and the like can be achieved by the present invention. Is possible.

Further, the food and drink of the present invention may contain other physiologically active ingredients and the like for the purpose of improving functions, in particular, synergistically improving the antitumor effect, assisting the antitumor effect, and improving the absorbability. it can. Although there is no particular limitation, for example, other antitumor components that can be expected to have synergistic effects, antioxidant components that are indirectly contributing to antitumor effects, and improved absorption in the body Examples include oily components for improving the efficiency of the effect, various vitamins, minerals, amino acids and the like for fortification.

Other oral antitumor components include gingerol, curcumin, bergamoti , Propaneoids such as ACA, flavone, catechin, quercetin, oral cocoanthocyanidin, luteolin, cardamonin, nobiletin, etc., flavonoids such as 力 rotin, astaxanthin and the like, and their carotenoids. Derivatives, dietary fiber such as lectin, alexin, ferulic acid, and the like. These anti-tumor components are preferable because a synergistic effect with the pentagonal triterpenes of the present invention can be expected.

The antioxidant component is not particularly limited as long as it is commonly used in foods and drinks. Examples thereof include vitamin C and its derivatives and salts thereof, tocoprol and tocotrienol and their derivatives, and dibutylhydroxytoluene. Tannins such as petroleum hydroxyanisole, disodium ethylenediaminetetraacetate, calcium disodium ethylenediaminetetraacetate, gallagic acid and ellagic acid, and derivatives thereof, sodium sulfite, sodium hyposulfite, sulfur disulfide, etc. Sulfuric acid compounds, such as furulic acid derivatives such as y-oryzanol, rutin and its derivatives, lignans such as sesamin, episesamine, sesaminol, sesamolin, and sesamol, and their carbohydrates, and carotenoids such as mono-rotin And their derivatives, flavones, Catechin, quercetin, isoquercetin, leucoanthocyanidin, genistin, genistein, 6 "-10-acetylgenistin, 6" -0-malonirgenistin, soybean, daidzein, 6 "-10-acetildizy Flavonoids, such as 6 "-0-malonyldizzin, glycitin, glycitin, 6" -10-acetylglycitin, 6 "-0-malonylglinitine, pellarin, quercetin, kenhue, miroesterol , Quinones such as ubiquinone and vitamin K, enzymes such as superoxide dims, power cod, glutathione peroxidase, mallow flower extract, aspergillus teleus extract, licorice oil extract Stuff, glove extract, guaiac fat, green coffee bean extract, rice bran oil extract, canna extract, sage Extract, Seri extract, Tempe extract, Rapeseed oil extract, Pimen Extract, Blueberry extract, Propolis extract, Pepper extract, Melalloy extract, Eucalyptus extract, Gentian extract, Buckwheat extract, Azuki extract, Rosemari extract, Olive cake extract and Soybean cake extract Extract, soybean germ extract, thiamines and their salts, riboflavin such as riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine such as pyridoxine dioctanoate, nicotinic acid amide, nicotinic acid beet Nicotinic acids such as carboxyl, pyrilvin, mannitol

, Tributofan, histidine, nordihydroguaiaretic acid, and the like. These antioxidants are said to have an indirect antitumor effect, and also have a total synergistic effect on the human body, etc. due to the anti-aging effect of lifestyle-related diseases due to the original antioxidant effect and the anti-aging effect. It is preferable because it can be expected.

The oily component includes vegetable oils such as soybean oil, rapeseed oil, sesame oil, and oil, animal oils such as radish, beef tallow, fish oil, and the like, but there is no particular limitation.For example, natural and chemical reactions and enzymatic reactions MCT, MLCT, diglyceride, monoglyceride II, structural fats and oils designed for the structure of fatty acids, etc.

There are no particular restrictions on various vitamins, minerals, amino acids, and the like for fortification, but those specified in the official food additive standard are desirable.

In addition, the foods and drinks of the present invention can be used by mixing and using raw materials used in ordinary foods and drinks. There is no particular limitation, but for example, various seasonings such as miso, soy sauce, sauce, kechi-yap, bouillon, grilled meat sauce, caramel, stew ingredients, soup ingredients, dashi ingredients, lard, tallow, Animal fats and oils such as milk fat, marine oils such as whale oil, sardine oil and nisin oil, soybean oil, rapeseed oil, cottonseed oil, rice oil, corn oil, sesame oil, peanut oil, sunflower oil, safflower oil, camellia oil, olive oil, Plant oils such as linseed oil, tung oil, castor oil, coconut oil, palm oil, cocoa butter, thickeners such as xanthan gum, sugar, granulated sugar, lactose, fructose, pudose sugar, sorbitol, sweetener such as honey, MSG (Monosodium glutamine) and other flavorings, rice vinegar, apple cider vinegar, sake spirit Vinegar such as vinegar, sour agents such as citric acid, malic acid, lactic acid, tartaric acid, synthetic preservatives such as sodium benzoate, wheat flour, defatted soybeans, cereal raw materials such as wheat bran, wheat germ, salt, pepper, flavor, etc. Is mentioned. Olive oil is particularly preferred because it contains maslinic acid and the like in the present invention. Olive oil or the like manufactured to contain maslinic acid, a physiologically acceptable salt thereof, or the like at a high level is preferable. The above components can be appropriately designed and blended depending on the purpose of use. An antitumor effect can be synergistically or complemented, or a preferred mode of use can be achieved depending on the type of absorption and effect. In addition, for example, isoflavones and derivatives thereof are excellent in water solubility, and generally have an antiestrogen inhibitory effect by acting on the living body at the same time as a specific pentacyclic triterbene which is an oil-soluble substance of the present invention. Synergistic effects are exerted through various water and lipid-mediated metabolic pathways, and the effects can be expected to be synergistic. Furthermore, foods and drinks for antitumor preparations, etc., which simultaneously contain the specific pentagonal triterpenes and isoflavonoids, etc., which are the objects of the present invention, have the same anti-oxidative and anti-estrogenic activity of isoflavonoids. It can be expected to be synergistically activated.

Specific examples of the food and drink for antitumor of the present invention are listed below, but the present invention is not limited thereto. The antitumor food / drink of the present invention is not particularly limited in its form, but may be in the form of a liquid food, an enteral nutrition food, a health food, a baby food, etc. in addition to a normal form. Can be. Specifically, Japanese sweets such as oysters, rice crackers, rice crackers, buns, candy, etc., cookies, biscuits, crackers, cereal foods, pies, castellas, donuts, puddings, sponge cakes, waffles, butter creams, custard creams, Various pastries such as cream puff, chocolate, chocolate confectionery, caramel, candy, queuing gum, jelly, hot cake, bread, confectionery bread, snacks such as potato chips, ice cream, ice candy, ice cream such as sherbet, lactic acid beverage, lactic acid beverage , Thick milk drink Drinks, fruit juice drinks, pulp drinks, functional drinks, soft drinks such as carbonated drinks, green tea, tea, coffee, cocoa, etc., and these drinks, alcoholic beverages such as sake, wine, brandy, whiskey, medicinal liquor Dairy products such as milk, fermented milk, processed milk, cheese, soybean processed foods such as soy milk, tofu, jam, fruit syrup pickles, flower pastes, peanut pastes, pulp pastes, pickles, udon noodles Grain products such as 麵, pass and evening dishes, meat products such as ham, sausage, bacon, dried sausage, beef jerky, hamburger etc., fish meat ham, fish sausage, fish and shellfish products such as kamaboko, chikuwa, and starch, fish , Dried fish such as shellfish, various sections such as bonito, mackerel, aji, salted fish such as sea urchin, squid, squid, fish, etc. , Seaweed, small fish, shellfish, wild vegetables, shiitake mushrooms, kelp and other tsukudani, curry, stew and other retort foods, miso, soy sauce, sauce, ketchup, puyon, grilled meat sauce, power rail, stew ingredients, soup Examples include various seasonings such as pu-no-moto and dashi-no-moto, cooked rice and other processed oils and fats such as mixed oils and fats, margarine, shortening, mayonnaise, and dressing, and various ranges and frozen foods containing mixed oils and fats. In particular, from the viewpoint of continuous ingestion, it can be said that cooked rice and various seasonings, and processed oils and fats such as mixed oils and fats, margarine, shortening, mayonnaise and dressing are preferred. The shape and properties are not particularly limited, and may be any of solid, semi-solid, gel, liquid, and powder.

Since pentacyclic triterpenes such as maslinic acid, erythrodiol, persolic acid, basol, phosphoric acid, and verin in the food and drink of the present invention are originally liposoluble substances, From the viewpoint of the food and drink of the present invention, prepared oils and fats, processed oil and fat processed foods and the like are also preferable. There is no particular limitation on such a prepared oil and fat. For example, natural or artificially obtained maslinic acid, erythrodiol, ursolic acid, baobaol, berylic acid, berylin, etc. are dissolved in ordinary fats and oils. Compressed plant seeds. ・ Adjusted extraction conditions to squeeze the pentacyclic triterpenes in the seeds. ・ Prepared oils and fats containing a high concentration of extracted oil and refined conditions. Adjust As a result, prepared oils and fats in which maslinic acid, erythrodiol, ursolic acid, polyvinyl alcohol, bery phosphoric acid, beryline, etc. which are present in the oil remain. In addition, the pentagonal triterpene-rich fats and oils can be mixed with other fats and oils, and in this case, a synergistic effect with the physiologically active effect of the trace components contained in the other fats and oils can be expected. ,

Since maslinic acid, erythritol, ursolic acid, evanyl, benulinic acid, and malic acid are also obtained from plants that are oil raw materials, it can be said that formulated oils and fats are preferable from the viewpoint of production. It can be said that processed oils and fats such as margarine, shorting, mayonnaise and dressing which are processed oils and fats are preferred.

Similarly, products using the above-mentioned blended fats and oils of the present invention are also good. Here, “use” refers to both use as a raw material and use as so-called blended oils and fats used for fried foods and stir-fries.

Here, there are no particular restrictions on the use of maslinic acid, erythrodiol, ursolic acid, ebaol, perinic acid, verin, etc. in foods and drinks. , Erythrodiol, persolic acid, polyvinyl alcohol, berylic acid, phosphorus, or a derivative having an alcohol ester group, a derivative having a fatty acid ester group, a derivative having an alkoxy group, a derivative having an alkoxymethyl group Is preferred. Since these are relatively fat-soluble, they can be suitably applied to oil-based foods and drinks. Naturally, maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, and physiologically acceptable salts of berylin or glycosides can also be blended. It is preferable to use an emulsifier o

In general, for water-based foods and drinks, maslinic acid, erythrodiol, persolic acid, baol, phosphoric acid, physiologically acceptable salts of verin, or glycosides are preferred. Since these are relatively water-soluble, it is preferable to use Can be applied to things. Of course, maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin, or a derivative thereof can be added, but in this case, an emulsifier is preferably used.

By eating and drinking the food and drink of the present invention, maslinic acid, erythrodiol, ursolic acid, ebaoyl, berylic acid, berylin, and their physiologically acceptable salts having an antitumor effect, The effect is obtained by absorbing those derivatives into the body. Since it is in the form of food and drink, it is preferable because it can be ingested continuously without the labor required for pharmaceuticals.

The present invention relates to an antitumor food and drink containing maslinic acid, erythrodiol, ursolic acid, baioruul, veriophosphoric acid, veraline, a physiologically acceptable salt thereof, or a derivative thereof. About things. These pentacyclic triterpenes are particularly excellent in antitumor effects such as a tumor cell growth inhibitory effect, a tumor cell killing effect, and a tumor cell metastasis inhibitory effect. It is preferable because the above-mentioned antitumor effect can be suitably enjoyed easily and continuously without a burden. In addition, the maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin, and the like in the present invention can be obtained from natural plants, and can be used safely in daily use. It is preferable because it gives the user a mentally refreshing feeling.

In addition, ingestion of maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, berylin, and their physiologically acceptable salts, or derivatives thereof, of the food and drink of the present invention. The dosage required to obtain an antitumor effect suitably depends on the form of ingestion, the sex, weight, physical condition, etc. of the subject, and is not particularly limited. For example, 0.001 g / day or more, preferably Is at least 0.001 g / day, more preferably at least 0.1 g / day, particularly preferably at least 0.5 lg / day, even more preferably at least 0.5 g / day, Particularly preferred is 1 g / day or more, most preferred Is greater than 2 g / day. Example

Hereinafter, the present invention will be further described with reference to examples, but the present invention is not limited to these examples.

As pentagonal triterpenes used in the examples, erythrodiol, persolic acid, baobaol, berylic acid, and berylin were purchased as reagents. The HPLC grade was used as is, and the others were dissolved in ethanol heated to the boiling point until saturated, then cooled and recrystallized, filtered and dried. The maslinic acid will be described below with reference to an actual example. The maslinic acid used was extracted and purified from an olive plant and confirmed to have a purity of 95%.

1 kg of dried fruits (including beef cattle) of domestically produced olive (01 ea europaea L.) were crushed, and 3 L of hexane was added and extracted for 3 hours. The defatted fruit (defatted cake) obtained by repeating this process four times was removed from the seeds, crushed, and extracted again with 5 times the amount of hexane for 3 hours to obtain 229 g of defatted cake from which oil was completely removed. Obtained . To this defatted lees, a 10-fold amount of a water-containing aqueous ethanol solution having an ethanol content of 60% by mass was added, and the mixture was extracted at room temperature with vigorous stirring for 3 hours. After filtering the whole amount, the filtrate was concentrated to dryness to obtain 112.7 g of an extract.

To 100 g of this extract, 2 L of water was added, and the mixture was vigorously stirred at room temperature for 1 hour. After processing the whole amount by centrifugation, the supernatant was removed by decantation, and the remaining precipitate was dried to obtain 10. Og of a concentrate.

Next, this concentrate was fractionated by silica gel column chromatography using a column packed with about 40 times (400 g) silica gel. First, 10 times the volume (400 OmL) of hexane: ethyl acetate == 3: 1 eluent of the packed gel was used. After eluting the necessary components, miscellaneous unnecessary components were further eluted with a 2.5-fold (100 OmL) hexane: ethyl acetate = 1: 1 eluent. Subsequently, the target maslinic acid was eluted with a 10-fold amount (400 OmL) of hexane: ethyl acetate = 1: 1 of the packed gel to obtain a crude maslinic acid fraction. After removing hexane and ethyl acetate from this fraction, vacuum drying was performed to obtain 1.96 g of a crude maslinic acid fraction.

Further, the crude maslinic acid fraction was purified by ODS column chromatography using a column packed with about 30 times (6 Og) of octyl decylsilicone gel. First, miscellaneous unnecessary components were eluted with a 10-fold (60 OmL) methanol: water = 8: 2 eluent of the packed gel. Subsequently, the desired maslinic acid was eluted with a 30-fold (180 OmL) methanol: water = 8: 2 eluent of the packed gel to obtain a purified maslinic acid fraction. After removing methanol from this fraction, vacuum drying was performed to obtain 1.5 lg of purified maslinic acid 1.

Here, from analysis by NMR, MS and GC, this purified maslinic acid 1 is partially in the form of sodium salt and potassium salt, and the rest is mostly in the form of free acid. The purity was confirmed to be 95% or more.

To 500 g of oiled residue (oiled cake) obtained by oiling an Italian olive (01 ea europaea L.), 10 times the amount of aqueous ethanol solution containing 65% by mass of ethanol was added. Extracted for 3 hours with vigorous stirring. After filtering the whole amount, the filtrate was concentrated to dryness to obtain 20.2 g of an extract.

1 L of n-butanol and 1 L of water were added to this extract, and the mixture was stirred for 10 minutes, and then separated into an n-butanol phase and an aqueous phase. After removing the n-butanol in the n-butanol phase, the residue was dried under vacuum to obtain 13.3 g of a concentrate.

The concentrate is then applied to a column packed with approximately 40 volumes (500 g) of silica gel. Fractionation was performed by using silica gel column chromatography. First, elution of various unnecessary components with a 10-fold volume (5000 mL) of hexane: ethyl acetate = 3: 1 eluent of the packed silica gel, and then a 2.5-fold volume (125 OmL) Miscellaneous unnecessary components were eluted with an eluent of xane: ethyl acetate = 1: 1. Subsequently, the desired maslinic acid was eluted with a 10-fold amount (500 OmL) of hexane: ethyl acetate = 1: 1 eluent of the packed silica gel to obtain a crude maslinic acid fraction. After removing hexane and ethyl acetate from this fraction, vacuum drying was performed to obtain 2.66 g of a crude maslinic acid fraction.

The crude maslinic acid fraction was further purified by ODS column chromatography using a column packed with about 30 times (80 g) of octyl decylsilicone gel. First, miscellaneous unnecessary components were eluted with a 10-fold (80 OmL) methanol: water = 8: 2 eluent of the packed gel. Subsequently, the target maslinic acid was eluted with an eluent of methanol: water = 8: 2 of 30 times the volume (240 OmL) of the packed gel to obtain a purified maslinic acid fraction. After removing the solvent from this fraction, vacuum drying was performed to obtain 2.06 g of purified maslinic acid 2.

Here, from the analysis by NMR, MS and GC, this purified maslinic acid 2 is partially in the form of a free acid, and most of the remaining is in the form of a salt such as sodium phosphate. The purity was found to be 97% or more.

The extraction residue of olive from Italy obtained in the olive oil production process (defatted cake obtained by further processing the squeezed residue in the extraction process) was added to 1 kg, 10 times the amount of ethanol was added, and the mixture was heated to 55 ° C. Extracted for 3 hours with vigorous stirring. After filtering the whole amount, the filtrate was concentrated to dryness to obtain 35 g of an extract.

Next, this extract was added to a column packed with about 40 volumes (1400 g) of silica gel. Was used for silica gel column chromatography. First, eluting miscellaneous unnecessary components with an eluent of about 10 times (14 L) hexane: ethyl acetate = 3: 1 of the packed silica gel, and then 2.5 times (350 OmL) The hexane: ethyl acetate = 1: 1 eluent is used to elute miscellaneous unnecessary components, and 10 times (14 L) of hexane: ethyl acetate = 1: 1 eluate of the packed silica gel. The desired maslinic acid was eluted to obtain a crude maslinic acid fraction. After removing hexane and ethyl acetate from this fraction, it was vacuum dried to obtain 5.90 g of a crude maslinic acid fraction. The crude maslinic acid fraction was further purified by ODS column chromatography using a column packed with 30-fold (180 g) octadecyl silica gel. First, 10-fold (1800 ml) Miscellaneous unnecessary components were eluted with the eluent of methanol: water = 8: 2). Subsequently, the desired maslinic acid was eluted with an eluent of methanol: water = 8: 2 30 times the amount of the packed gel (5400 ml) to obtain a purified maslinic acid fraction. After removing methanol and water from this fraction, it was dried under vacuum to obtain 5.36 g of purified maslinic acid 3.

Here, from the analysis of NMR, MS, etc., this purified maslinic acid 3 is partially purified sodium silicate and potassium salt, and most of the remaining maslinic acid is free acid. It was confirmed. The purity was measured by GC, and it was confirmed that the purity as maslinic acid was 97% or more.

Derivatives of maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, and veline were obtained as follows.

<Synthesis Example 1> Ethyl maslinate

Dissolve 4.5 g of maslinic acid and 1.0 g of triethylamine in 5 OmL of chloroform, and dissolve 1.1 g of thionyl chloride in 1 OmL of chloroform and add dropwise under ice-cooling. Stirred for 1 hour. Subsequently, 3.2 g of ethanol was added, and A solution prepared by dissolving 1.0 g of tilamine in 1 OmL of chloroform was added dropwise under ice-cooling, and the mixture was stirred for 3 hours. After the completion of the reaction, the solution in the form of chloroform was extracted, and the crude reaction product obtained by distilling the form from the pore was purified by silica gel column chromatography to obtain 3.5 g of ethyl maslin ester.

<Synthesis Example 2> 2,3-0-Diacetyl-maslinic acid

2.0 g of maslinic acid was dissolved in 10 OmL of pyridine, 50 mL of acetic anhydride was added, and the mixture was stirred overnight. After distilling off pyridine and acetic anhydride, the residue was dissolved in ether, and the ether phase was washed once with a 1N aqueous hydrochloric acid solution, once with a saturated sodium hydrogen carbonate solution, and three times with pure water, and then sulfuric acid. Magnesium was added and left overnight. The crude reaction product obtained by removing magnesium sulfate by filtration and distilling off ether was purified by silica gel column chromatography to obtain 2.2 g of 2,3-0-diacetylmethyl maslinic acid. Was. Synthetic Example 3> 2,3 -—— di-triethylsilyl monomass triethylsilyl phosphate

1.0 g of maslinic acid was dissolved in 20 OmL of anhydrous dimethylformamide, 144.Omg of imidazole and 350 L of triethylsilyl chloride were added at 0 ° C, sealed, and stirred for 2 hours. After distilling off the dimethylformamide, the residue was dissolved in ether, and the ether phase was washed once with a 1N aqueous hydrochloric acid solution, once with a saturated sodium hydrogencarbonate solution, and three times with pure water, and then sulfuric acid. Magnesium was added and left overnight. Magnesium sulfate was removed by filtration, and the crude reaction product obtained by evaporating the ether was purified by silica gel column chromatography to obtain 1.5 g of 2,3-0-diethylsilyl-maslin triethylsilyl ester. Was. Synthesis Example 4> 2,3-0-di-stearoyl-massethyl phosphate Dissolve 1.0 g of ethyl methacrylate obtained in Synthesis Example 1 in 5 OmL of anhydrous toluene, add 5.Og of triethylamine, add stearin The mixture was stirred for 1 hour while gradually adding 6. Og of acid chloride under ice cooling, and stirred for 9 hours while gradually returning to room temperature. An appropriate amount of 1 N hydrochloric acid aqueous solution was added, and the mixture was extracted with ether. The ether phase was further washed once with a saturated sodium hydrogen carbonate solution and three times with pure water, and then added with magnesium sulfate and left overnight. The crude product obtained by removing magnesium sulfate by filtration and distilling ether was purified by silica gel column chromatography to obtain 1.2 g of 2,3-0-di-stearoyl-mass ethyl phosphate. Was. Synthesis Example 5> 3, 28—0—Diacetylethyl diol

5.0 g of erythrodiol was dissolved in 250 mL of pyridine, 100 mL of acetic anhydride was added, and the mixture was stirred overnight. After distilling off pyridine and acetic anhydride, the residue was dissolved in ether, and the ether phase was washed once with a 1N aqueous hydrochloric acid solution, once with a saturated sodium hydrogen carbonate solution, and three times with pure water. Magnesium sulfate was added and left overnight. The crude reaction product obtained by removing magnesium sulfate by filtration and distilling off the ether was purified by silica gel column chromatography to obtain 5.4 g of 3,28-0-diacetyl-erythrodiol. . Synthesis Example 6> Ethyl persoleate

5.0 g of persolic acid and 1.1 g of triethylamine were dissolved in 5 OmL of chloroform, and 1.2 g of thionyl chloride was dissolved in 1 OmL of chloroform. Stir for 1 hour. Subsequently, 3.5 g of ethanol was added, and a solution of 1.1 g of triethylamine dissolved in 1 OmL of chloroform was added dropwise under ice-cooling, followed by stirring for 3 hours while dropping. After the reaction is completed, extract the dissolved form of The crude reaction product obtained by distilling off the lump was purified by silica gel gel chromatography to obtain 3.8 g of ethyl ethyl uronate. Synthetic Example 7> 3, 28-0-Diacetyl-vinyl

5.0 g of Baioru was dissolved in 250 mL of pyridine, 100 mL of acetic anhydride was added, and the mixture was stirred overnight. After distilling off pyridine and acetic anhydride, the residue was dissolved in ether, and this ether phase was washed once with a 1N aqueous hydrochloric acid solution, once with a saturated sodium hydrogen carbonate solution, and three times with pure water. Then, magnesium sulfate was added and left overnight. The crude reaction product obtained by removing the magnesium sulfate by filtration and distilling the ether was purified by silica gel column chromatography, and 5.1 g of 3,28-0-diacetyl-vinyl was obtained. Obtained.

<Synthesis Example 8> Bethyl phosphate

5.0 g of benzoic acid and 1.1 g of triethylamine were dissolved in 5 OmL of chloroform, and 1.2 g of thionyl chloride was dissolved in 1 OmL of chloroform, and added dropwise under ice-cooling. While stirring for 1 hour. Subsequently, 3.5 g of ethanol was added, and a solution prepared by dissolving 1.1 g of triethylamine in 1 OmL of chloroform was added dropwise under ice-cooling, followed by stirring for 3 hours while dripping. After the completion of the reaction, the solution in the form of chloroform was extracted, and the crude reaction product obtained by distilling the form from the form was purified by silica gel column chromatography to obtain 3.4 g of ethyl ethyl phosphate.

3, 28—Pegasecil-Bellin

5.0 g of betaline was dissolved in 25 OmL of pyridine, 10 OmL of acetic anhydride was added, and the mixture was stirred overnight. After distilling off pyridine and acetic anhydride, the residue was dissolved in ether. The ether phase was washed once with a 1N aqueous hydrochloric acid solution, once with a saturated sodium hydrogen carbonate solution, and three times with pure water, and then added with magnesium sulfate and left overnight. The crude reaction product obtained by removing magnesium sulfate by filtration and distilling ether off was purified by silica gel column chromatography, and 5.7 g of 3,28-0-diacetyl-peridoline was obtained. Obtained. Example 1 Tumor cell growth inhibition test and tumor cell death test

The tumor cell growth inhibition test and the tumor cell death test were performed by the following methods. 2 ml / we 11 of the medium was taken in a 6-well plate, a predetermined amount of B-16 melanoma cells were inoculated, and allowed to stand and cultured at 37 ° C and a carbon dioxide concentration of 5%. The next day, a sample sample preparation solution was added and mixed to a predetermined concentration, and the culture was continued. The medium was changed on the fifth day of the culture, and the sample preparation solution was added again. On the next day, the medium was removed, the cells were collected, washed with PBS (phosphate buffered saline), the number of surviving cells was counted, and the cell growth rate was calculated from the following equation (1). From this cell growth rate, the effect of suppressing tumor cell growth and the effect of killing tumor cells were evaluated. This was compared with the cell growth rate without a sample (control). Cell proliferation rate (%) = (A ÷ B) 100 (1)

A: Number of surviving cells at each sample addition

B: Number of surviving cells in control

Add maslinic acid, erythrodiol, persolic acid, evanol, benulinic acid, veline and their physiologically acceptable salts or their derivatives to the concentrations shown in Table 1, and add Evaluation was performed based on the cell proliferation rate during cell culture. As a comparison, the cell growth rate when oleanolic acid, monoamylin, hyamylin and role was added was similarly calculated and evaluated. The results are shown in Table 1 below.

From Table 1, it was found that ^ amylin, α-amylin, and ruluol, which were compared, had no tumor cell growth inhibitory effect. In addition, oleanolic acid, which has an inhibitory activity on carcinogenesis promoter, only exhibited a very weak tumor cell growth inhibitory effect at a high concentration. On the other hand, maslinic acid, erythrodiol, ursolic acid, ebaol, diphosphoric acid, vegulin and their physiologically acceptable salts, or derivatives thereof, have a very low tumor cell growth inhibitory effect. I knew it was strong. In particular, in the case of maslinic acid, ursolic acid and their physiologically acceptable salts, or derivatives thereof, extremely strong tumor cells can be obtained at a concentration of twice or more that exerts a tumor cell growth inhibitory effect. Demonstrated the killing effect. This was an effect that was not seen at all with oleanolic acid,? -Amylin, -amylin, and ruol.

This results in maslinic acid, erythritol, persolic acid, baool, Phosphoric acid, betaline and their physiologically acceptable salts, or derivatives thereof, have been found to have very excellent tumor cell growth inhibitory and tumor cell killing effects.

Example 2 Melanoma Metastasis Inhibition Test

The melanoma metastasis suppression test was performed by the following method. C57BL 16 female mice (6 weeks old, average body weight 25 g) were pre-fed for 1 week on a powdered diet with AIN-93 composition, and then divided into 5 groups (8 mice per group) so that the average body weight was uniform. Separately prepared suspensions of B16 melanoma cells were injected intravenously into each mouse. On this day as day 0, the mice in each group were allowed free access to the diets shown in Tables 2 and 3. However, if the total amount was less than 100, the shortage was supplemented with corn starch. On day 29 after the injection of B16 melanomas cells, the lungs were removed and the number of metastatic cancer foci that had metastasized to the lungs was counted. From this metastasis suppression rate, the effect of suppressing tumor cell metastasis was evaluated.

Table 2

Metastasis inhibition rate (%) = (DC) ÷ Dx 100 (2)

C: Average number of metastatic cancer foci in each group

D: Average number of metastatic cancer foci in control group Using cottonseed oil as a control, maslinic acid, erythrodiol, persolic acid, basol, veratic acid, perrin and their physiologically acceptable salts or their derivatives, and the metastasis inhibition rate by the doses shown in Table 3 Was evaluated. As a comparison, the evaluation of the transfer inhibition rate when oleanolic acid was added was similarly performed. Table 3 below shows the evaluation results. Table 3

As is evident from Table 3, maslinic acid, erythrodiol, persolic acid, palesol, vertulinic acid, perrinic acid and their physiologically acceptable salts, or their derivatives, were compared to the control group. Significantly (P <0.05) metastasized to the lung. Administration of oleanolic acid had no significant effect. The results indicate that maslinic acid, erythrodiol, ursolic acid, evanol, berylic acid, berylin and their physiologically acceptable salts, or their derivatives, could be taken orally. It was revealed that an effective tumor cell metastasis inhibitory effect could be enjoyed.

Hereinafter, examples of the food and drink in the present invention will be described. Types of food and drink included in them The contents of maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin and their physiologically acceptable salts or their derivatives are not limited to the following. . Example 3 Edible oils and fats

Purified maslinic acid 15.0 g

EXV. Olive oil 100.0 g Add purified maslinic acid 1 to EXV. (Extra virgin) orifice oil at the above mixing ratio, and keep the whole at 60 ° C while using a stirrer to clarify the whole. The mixture was thoroughly mixed and dissolved until it became, to produce edible oils and fats. Example 4 Dressing

Water 46.6 g Xansu gum gum 0.1 g Fructose-glucose liquid sugar 5.0 g Salt 5.0 g

MSG 0.3 g Rice vinegar (acidity 10%) 10.0 g Pepper suitable amount Purified maslinic acid of Production Example 2 21.0 g Soybean salad oil 32.0 g Put into a warmable container equipped with a stirrer, heat the product to 90 ° C while stirring at 100 rpm using a propeller stirrer, and maintain the product temperature at 90 ° C. Stirring was performed for minutes. Then, cool until the temperature reaches 20 ° C and dressing with soybean salad oil. Profit

Was

Example 5 Soft drink

3, 28-0-Diacetyl erythritol of Synthesis Example 5 0 g g Honey 150 g g citrate 0 1 sdl-malic acid 0 1 s

D-sorbitol solution (70%) 100 g Sodium benzoate 0 1 g Fragrance

Remaining amount of purified water: 100 g The above ingredients were mixed uniformly to obtain a health drink. Example 6 Cereal food

Synthetic Example 7, 3, 28-0-diacetyl-baobaol 15.0 g flour 30.0 g defatted soybean 18.5 g wheat bran 15.0 g wheat germ 11.5 g granulated sugar 10.0 g The mixture at the above mixing ratio was added with water, molded, and heated and dried in an oven to obtain a spherical cereal food. Example 7 Edible oils and fats

Purified maslinic acid of Production Example 3 3 10.0 g EXV. Olive oil 100.0 g Add purified maslinic acid 3 to EXV. (Extra virgin) olive oil at the above mixing ratio, and keep the entire temperature clear at 60 ° C using a stirrer. Thorough mixing and dissolution were performed to produce edible oils and fats. Example 8 Edible oils and fats

Purified maslinic acid of Production Example 1 15.0 g Soybean oil 100.0 g At the above mixing ratio, refined maslinic acid 1 was added to soybean oil, and while maintaining the temperature at 60 ° C, the whole was stirred using a stirrer. The mixture was thoroughly mixed and dissolved until it became clear, and an edible oil mixture was produced. Example 9 Margarine

42 0 g

Hardened rapeseed oil 42 0 g

140 g of water

0 5 g salt

0 5 g

Monoglyceride 0 4 g

106 g of purified maslinic acid from Production Example 1

Spice

Carotene

The above-mentioned raw materials were mixed by a conventional method, and quenched and kneaded using a convenience store overnight to obtain margarine. Example 10 Mayonnaise

Soy salad oil 74.0 g

8.4 g of water Sugar 10 g Sodium glutamate 0 3 g

Powder mass 1 3 g

10 g of salt

Rice vinegar 40 g

Purified maslinic acid of Production Example 2 210 g

Salted egg yolk 100 g

At the above mixing ratio, first, the raw materials excluding soybean salad oil and salted egg yolk were heated to 90 ° C while mixing and stirring, and stirred for 25 minutes while maintaining the temperature at 90 ° C. After cooling to 20 ° C, soybean salad oil and salted egg yolk were combined and stirred under reduced pressure to obtain mayonnaise.

According to the food and drink of the present invention, specific pentacyclic triterpenes such as maslinic acid, erythrodiol, persolic acid, ゥ baol, and ゥ are easily and continuously prepared without requiring time and labor. Phosphoric acid, betaline and their physiologically acceptable salts or their derivatives can be ingested, resulting in tumor cell growth inhibitory effect, tumor cell killing effect, tumor cell metastasis inhibitory effect, etc. An antitumor effect can be suitably enjoyed. Further, since the specific pentacyclic triterpenes in the present invention can be obtained from nature, it can be said that their use has a sense of security.

Claims

The scope of the claims

1. Maslinic acid, erythrodiol, ursolic acid, benzoyl, and beryric acid

An antitumor food / drink comprising, as an active ingredient, a compound selected from bevelin, a physiologically acceptable salt thereof, or a derivative thereof.

2. Maslinic acid, erythrodiol, ursolic acid, baioruul, persulphic acid

A food or beverage for suppressing tumor cell growth, comprising as an active ingredient a compound selected from bevelin, a physiologically acceptable salt thereof, or a derivative thereof.

3. Maslinic acid, erythrodiol, ursolic acid, benzoyl, beric acid

A food / beverage composition for killing tumor cells, comprising as an active ingredient a compound selected from the group consisting of bevelin, physiologically acceptable salts thereof, and derivatives thereof.

4. Maslinic acid, erythrodiol, ursolic acid, ebaol, diphosphoric acid

A food or beverage for suppressing tumor cell metastasis, which comprises, as an active ingredient, a compound selected from bevelin, a physiologically acceptable salt thereof, or a derivative thereof.

5. The maslinic acid, erythrodiol, ursolic acid, evanol, berylic acid, bellin and their physiologically acceptable salts are those isolated from natural products. The food or drink according to any one of the above.

6. The content of the compound selected from maslinic acid, erythrodiol, persolic acid, evanolic acid, berylic acid, bellin and their physiologically acceptable salts, or their derivatives, is determined by the total mass of the food and drink. The food or drink according to any one of claims 1 to 4, which is 0.5% by mass or more based on the weight of the food and drink.

7. The derivative of maslinic acid, erythrodiol, ursolic acid, polyvinyl alcohol, berylic acid or phosphorus acid is a derivative having an alcohol ester group or a fatty acid ester group. Food and drink according to item 1.

8. The food or drink according to any one of claims 1 to 4, wherein the food or drink is a processed food.

9. The food or drink according to claim 8, wherein the processed food is a prepared oil or fat or a processed oil or fat.

10. The food or drink according to claim 9, wherein the processed oil or fat is margarine, shortening, mayonnaise or dressing.

11. The food or drink according to any one of claims 1 to 4, wherein the food or drink is a soft drink.

12. All or part of the maslinic acid, erythrodiol, ursolic acid, benzoyl acid, peronic acid, or verin is present in the form of a physiologically acceptable salt thereof and / or a derivative thereof. The food or drink according to any one of claims 1 to 4, wherein

13 3. An edible oil or fat containing maslinic acid in an amount of 1% by mass or more, which is obtained by extracting olive defatted cake with an ethanol solution, concentrating it by drying, and then purifying it by chromatography.

14. A dressing containing at least 1% by mass of maslinic acid, which is obtained by extracting oily cake of olive with an ethanol solution, drying, condensing, and then chromatographing.

15 5. Tumor prevention containing a compound selected from the group consisting of maslinic acid, erythrodiol, persolic acid, valine, vellic acid, perlin and their physiologically acceptable salts, or derivatives thereof For food and drink.

1 6. Maslinic acid, erythrodiol, persolic acid, ebaol, and perphosphoric acid

Use as a food or drink for tumor prevention, comprising a compound selected from the group consisting of beverin, physiologically acceptable salts thereof, and derivatives thereof.

1 7. Tumor treatment containing a compound selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, verin and their physiologically acceptable salts, or derivatives thereof For food and drink.

1 8. Tumors containing a compound selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, evanol, berlinic acid, berlin and their physiologically acceptable salts, or derivatives thereof Use as therapeutic food and drink.