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WO2002052956A1 - Boisson ou aliment antitumoral - Google Patents

Boisson ou aliment antitumoral Download PDF

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Publication number
WO2002052956A1
WO2002052956A1 PCT/JP2001/011374 JP0111374W WO02052956A1 WO 2002052956 A1 WO2002052956 A1 WO 2002052956A1 JP 0111374 W JP0111374 W JP 0111374W WO 02052956 A1 WO02052956 A1 WO 02052956A1
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WO
WIPO (PCT)
Prior art keywords
acid
food
drink
erythrodiol
maslinic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2001/011374
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English (en)
Japanese (ja)
Inventor
Gou Shinohara
Noriyasu Kuno
Toshiyuki Inui
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nisshin Oillio Group Ltd
Original Assignee
Nisshin Oil Mills Ltd
Nisshin Oillio Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nisshin Oil Mills Ltd, Nisshin Oillio Ltd filed Critical Nisshin Oil Mills Ltd
Priority to JP2002553920A priority Critical patent/JPWO2002052956A1/ja
Publication of WO2002052956A1 publication Critical patent/WO2002052956A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis

Definitions

  • 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.
  • 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
  • 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.
  • 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.
  • a food or drink for suppressing tumor cell proliferation is provided.
  • 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.
  • a compound selected from maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin and a physiologically acceptable salt thereof, or a derivative thereof is provided.
  • maslinic acid erythrodiol, ursolic acid, polyvinyl alcohol, veric acid, and phosphorus
  • maslinic acid erythrodiol, ursolic acid, polyvinyl alcohol, veric acid, and phosphorus
  • 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.
  • 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.
  • an aqueous food and drink such as a beverage can also be obtained.
  • 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.
  • 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.
  • 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.
  • 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 ⁇ Pharyngo-pharyngeal cancer, etc.
  • Sigmoid colon cancer ⁇ Ascending colon cancer ⁇ Transverse colon cancer ⁇ Cecal cancer ⁇ Colorectal cancer such as descending colon cancer, hepatocellular carcinoma ⁇ Intrahepatic ductal carcinoma ⁇ Hepatoblastoma ⁇ Hepatic duct ⁇ 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 ⁇ ⁇ Ilmus tumor ⁇ Kidney cancer such as renal angiomyolipoma, seminoma ⁇ fetal carcinoma ⁇ yolk cystoma ⁇ Choriocarcinoma ⁇ 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,
  • 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.
  • 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.
  • 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.
  • an aqueous food and drink such as a drink, for example, a soft drink
  • a drink for example, a soft drink
  • 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.
  • 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.
  • oleanan triterpenes 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.
  • 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.
  • oleanolic acid and maslinic acid have extremely similar structures, but their antitumor effects are incomparably different.
  • 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.
  • 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.
  • alkali metal salts such as sodium, potassium, and lithium
  • alkaline earth metal salts such as calcium, magnesium, barium, and zinc.
  • 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.
  • alkali metal salts alkylamine salts, alkanolamine salts and basic amino acid salts are preferred.
  • 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.
  • the derivative is not particularly limited as long as it is a possible derivative.
  • a derivative having an alcohol ester group, a fatty acid ester Derivatives having an alkoxy group, derivatives having an alkoxymethyl group, and glycosides.
  • 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.
  • derivatives of the present invention can be derivatized again and their salts can be used.
  • maslinic acid, erythrodiol, persolic acid, vaoyl, verophosphoric acid, and veraline can be converted into appropriate physiologically acceptable salts and derivatives.
  • 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.
  • the alcohol at this time 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.
  • fatty acids 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • maslinic acid and erythrodiol are one type of oleane-based triterpenes, and are substances already known to be present in various plants.
  • 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 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.
  • 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.
  • the term "olives" means an oriental plant and a product obtained in the Z or olive oil and Z or ore oil production process.
  • 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.
  • any one of the derivatives is derivatized, such as methyl maslinate, ethyl maslinate, n-propyl maslinate, isopropylhandedte, 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— ⁇ -1 Myristyl monomassic acid , 3-0—palmityl-maslinic acid, 3-0—palmi toreyl-mass P
  • 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.
  • 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.
  • 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.
  • 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.
  • physiologically acceptable salts and derivatives of erythrodiol are the same as described above.
  • 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-erythrod
  • 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.
  • 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.
  • 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 ⁇ 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.
  • persolic acid 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.
  • ursolic acid the physiologically acceptable salts and derivatives thereof are the same as described above.
  • 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.
  • any one of which is derivatized may be methyl ursolic acid, methyl ethyl persole, ⁇ -propyl ursolic acid, isopropyl ursolic acid, isopropyl ursolic acid, Luic acid ⁇ -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
  • D Galactopyranosyl monoursolic acid
  • 3 0—3—D—Glucuronovirano Siluric acid and the like.
  • D Galactopyranosyl monoursolic acid
  • 3 0—3—D—Glucuronovirano Siluric acid and the like.
  • 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 ⁇ 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.
  • 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.
  • 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—0
  • 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.
  • 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.
  • 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
  • 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 /?
  • 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.
  • 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.
  • those obtained from nature such as birch bark are preferred.
  • 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
  • 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.
  • 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.
  • 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.
  • 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 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.
  • 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.
  • hydrophobic organic solvents examples 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.
  • 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.
  • 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 ⁇ 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 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.
  • 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.
  • 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.
  • 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.
  • HPLC high-performance liquid chromatography
  • any method can be used.
  • 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.
  • 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.
  • HPLC High-performance liquid chromatography
  • maslinic acid and / or its physiologically acceptable salt can be very concentrated and can be obtained in a state where impurities have been removed.
  • 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.
  • 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.
  • the concentration treatment can be preferably repeated, and different concentration treatments can be combined.
  • the fractionation / purification treatment preferably, the fractionation / purification treatment can be preferably repeated, and further, different fractionation / purification treatments can be combined.
  • fractionation and purification may be performed after concentration, and fractionation and purification may be performed after fractionation and purification.
  • a fractionation / purification treatment can be performed, and the concentration treatment can be further performed.
  • a combination other than the above-mentioned combination may be used.
  • 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.
  • the aqueous solution can be subjected to treatment such as addition of water and stirring if necessary. .
  • 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.
  • 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.
  • water is added to the dried extract in the same manner as described above, and the hydrophobic organic solvent is added.
  • concentration treatment can be performed by liquid-liquid partitioning with a water-hydrophobic organic solvent.
  • 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.
  • 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 is preferably 95% or more, more preferably 95% to 99.99%. The content can be measured by, for example, gas chromatography.
  • 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.
  • the concentration of maslinic acid and Z or a physiologically acceptable salt thereof can be adjusted.
  • 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.
  • 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.
  • maslinic acid and / or a physiologically acceptable salt thereof can be obtained from an olive plant.
  • 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.
  • these mixtures can be directly blended with the food and drink of the present invention.
  • maslinic acid and / or a physiologically acceptable salt thereof are also preferable since a synergistic effect can be expected in the present invention.
  • maslinic acid and / or its physiologically acceptable salts are extracted, separated and purified, etc.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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, ⁇ 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.
  • 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.
  • oleanolic acid which is known as a carcinogenesis promoter inhibitor
  • administration of oleanolic acid 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
  • the control (non-administration) group has the administration of the acid, ebaol, diphosphate, veline and their physiologically acceptable salts, or their derivatives. Suppress metastasis of melanoma.
  • 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. .
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • beverages and the like are often commercialized in aqueous or emulsified systems.
  • pentacyclic triterpenes can be suitably converted to physiologically acceptable salts or glycosides thereof. Can be blended.
  • 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.
  • 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.
  • oral antitumor components include gingerol, curcumin, bergamoti , Propaneoids such as ACA, flavone, catechin, quercetin, oral cocoanthocyanidin, luteolin, cardamonin, nobiletin, etc., flavonoids such as ⁇ 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 ubi
  • 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.
  • 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.
  • natural and chemical reactions and enzymatic reactions MCT, MLCT, diglyceride, monoglyceride II, structural fats and oils designed for the structure of fatty acids, etc.
  • the foods and drinks of the present invention can be used by mixing and using raw materials used in ordinary foods and drinks.
  • 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 flavor
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 G
  • 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.
  • prepared oils and fats, processed oil and fat processed foods and the like are also preferable.
  • 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.
  • 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.
  • blended fats and oils of the present invention are also good.
  • “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.
  • maslinic acid 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.
  • 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.
  • 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.
  • oleanolic acid which has an inhibitory activity on carcinogenesis promoter, only exhibited a very weak tumor cell growth inhibitory effect at a high concentration.
  • 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.
  • 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.
  • 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.
  • 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.
  • specific pentacyclic triterpenes such as maslinic acid, erythrodiol, persolic acid, ⁇ baol, and ⁇ 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.
  • 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.

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  • Food Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
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  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Steroid Compounds (AREA)
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Abstract

L'invention concerne une boisson ou un aliment antitumoral contenant comme principe actif un composé sélectionné dans le groupe constitué par l'acide maslinique, des érythro-diols, l'acide ursolique, l'uvaol, l'acide bétulinique, la bétuline, des sels physiologiquement acceptables de celui-ci, et des dérivés de celui-ci.
PCT/JP2001/011374 2000-12-27 2001-12-25 Boisson ou aliment antitumoral Ceased WO2002052956A1 (fr)

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057224A1 (fr) * 2001-12-28 2003-07-17 The Nisshin Oillio, Ltd. Inducteur d'apoptose
WO2005027891A1 (fr) * 2003-09-22 2005-03-31 Use-Techno Corporation Accelerateur de secretion d'insuline de base
JP2006508968A (ja) * 2002-11-21 2006-03-16 武漢利元亨薬物技術有限公司 ウルソル酸−大豆レシチン凍結乾燥ナノ粒子注射剤およびその製造方法
JP2006515314A (ja) * 2003-04-22 2006-05-25 ラボラトリオ キミコ インターナショナール ソシエタ ペル アチオネ チオクト酸のｌ−カルニチンとの塩基性塩
ES2264880A1 (es) * 2005-03-18 2007-01-16 Universidad De Granada Aceite de oliva dietetico por reincorporacion de ingredientes naturales procedentes de la aceituna.
ES2267403A1 (es) * 2005-08-17 2007-03-01 Universidad De Granada Composicion nutraceutica obtenida de triterpenos naturales de la olea europaea.
WO2008102047A1 (fr) * 2007-02-22 2008-08-28 Universidad De Granada Composition d'huile d'olive et son utilisation comme aliment fonctionnel
WO2009121992A2 (fr) 2008-04-03 2009-10-08 Biomaslinic S.L. Utilisation de l'acide maslinique dans le traitement de pathologies et de leurs symptômes par inhibition de cox-2
JP2014005246A (ja) * 2012-06-26 2014-01-16 Uha Mikakuto Co Ltd 新規ケルセチン誘導体

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6439973A (en) * 1987-08-06 1989-02-10 Taiyo Kagaku Kk Drink composition
JPH0967249A (ja) * 1995-06-22 1997-03-11 Nippon Flour Mills Co Ltd グリセロリン酸脱水素酵素阻害剤
JPH10265328A (ja) * 1997-03-27 1998-10-06 Nippon Flour Mills Co Ltd 化粧料、ペットフード、リパーゼ阻害剤及びそれを含む食品

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6439973A (en) * 1987-08-06 1989-02-10 Taiyo Kagaku Kk Drink composition
JPH0967249A (ja) * 1995-06-22 1997-03-11 Nippon Flour Mills Co Ltd グリセロリン酸脱水素酵素阻害剤
JPH10265328A (ja) * 1997-03-27 1998-10-06 Nippon Flour Mills Co Ltd 化粧料、ペットフード、リパーゼ阻害剤及びそれを含む食品

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057224A1 (fr) * 2001-12-28 2003-07-17 The Nisshin Oillio, Ltd. Inducteur d'apoptose
JP2006508968A (ja) * 2002-11-21 2006-03-16 武漢利元亨薬物技術有限公司 ウルソル酸−大豆レシチン凍結乾燥ナノ粒子注射剤およびその製造方法
JP4896401B2 (ja) * 2002-11-21 2012-03-14 武漢利元亨薬物技術有限公司 ウルソル酸−大豆レシチン凍結乾燥ナノ粒子注射剤およびその製造方法
JP2006515314A (ja) * 2003-04-22 2006-05-25 ラボラトリオ キミコ インターナショナール ソシエタ ペル アチオネ チオクト酸のｌ−カルニチンとの塩基性塩
WO2005027891A1 (fr) * 2003-09-22 2005-03-31 Use-Techno Corporation Accelerateur de secretion d'insuline de base
ES2264880B1 (es) * 2005-03-18 2008-02-01 Universidad De Granada Aceite de oliva dietetico por reincorporacion de ingredientes naturales procedentes de la aceituna.
ES2264880A1 (es) * 2005-03-18 2007-01-16 Universidad De Granada Aceite de oliva dietetico por reincorporacion de ingredientes naturales procedentes de la aceituna.
WO2007020313A3 (fr) * 2005-08-17 2007-05-03 Univ Granada Composition nutraceutique obtenue a partir de triterpenes naturels de l'olea europaea
ES2267403B1 (es) * 2005-08-17 2008-03-16 Universidad De Granada Composicion nutraceutica obtenida de triterpenos naturales de la olea europaea.
ES2267403A1 (es) * 2005-08-17 2007-03-01 Universidad De Granada Composicion nutraceutica obtenida de triterpenos naturales de la olea europaea.
WO2008102047A1 (fr) * 2007-02-22 2008-08-28 Universidad De Granada Composition d'huile d'olive et son utilisation comme aliment fonctionnel
ES2311394A1 (es) * 2007-02-22 2009-02-01 Universidad De Granada Alimento funcional obtenido por reincorporacion de ingredientes naturales de la aceituna al aceite de oliva.
ES2311394B2 (es) * 2007-02-22 2009-10-21 Universidad De Granada Alimento funcional obtenido por reincorporacion de ingredientes naturales de la aceituna al aceite de oliva.
WO2009121992A2 (fr) 2008-04-03 2009-10-08 Biomaslinic S.L. Utilisation de l'acide maslinique dans le traitement de pathologies et de leurs symptômes par inhibition de cox-2
JP2014005246A (ja) * 2012-06-26 2014-01-16 Uha Mikakuto Co Ltd 新規ケルセチン誘導体

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