WO2002078468A1 - Aliment ou boisson pour maladie ou trouble vasculaire - Google Patents

Aliment ou boisson pour maladie ou trouble vasculaire Download PDF

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Publication number
WO2002078468A1
WO2002078468A1 PCT/JP2002/003188 JP0203188W WO02078468A1 WO 2002078468 A1 WO2002078468 A1 WO 2002078468A1 JP 0203188 W JP0203188 W JP 0203188W WO 02078468 A1 WO02078468 A1 WO 02078468A1
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Prior art keywords
food
mass
acid
drink
physiologically acceptable
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PCT/JP2002/003188
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English (en)
Japanese (ja)
Inventor
Hisami Shinohara
Gou Shinohara
Noriyasu Kuno
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The Nisshin Oillio, Ltd.
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Priority to JP2002576745A priority Critical patent/JPWO2002078468A1/ja
Publication of WO2002078468A1 publication Critical patent/WO2002078468A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Definitions

  • Yoshiaki Akira is used for vascular smooth muscle cell proliferation and / or vascular smooth muscle cell migration, cell proliferative vascular lesions such as intimal hyperplasia and arteriosclerosis, and blood vessels such as arteriosclerosis and restenosis after percutaneous coronary angioplasty.
  • the present invention relates to foods and drinks that exhibit the effects of prevention and / or treatment of disorders.
  • ischemic heart diseases such as angina and myocardial infarction
  • cerebrovascular diseases such as stroke and cerebral embolism
  • Japan the above diseases are rapidly increasing as one of the causes of death due to the westernization of the diet and the aging of the population.
  • vascular lesions such as narrowing of the vascular lumen and loss of elasticity of the vascular wall caused by arteriosclerosis.
  • Atherosclerosis depends on not a single but a plurality of factors and triggers, but it can be broadly divided into two main factors.
  • One is the aggregation of various reticulo-endothelial cells due to arterial endothelial damage, the subsequent release of vascular smooth muscle cell growth factor, and the migration of vascular smooth muscle cells from the media to the atherosclerotic lesions and
  • the other is the transformation of vascular endothelial cells, vascular smooth muscle cells due to hyperlipidemia containing cholesterol, and proliferation in atherosclerotic foci. That is, migration of vascular smooth muscle cells to the intima and cell fibrous thickening caused by proliferation in the intima cause cell proliferative vascular lesions such as narrowing of the blood vessel lumen.
  • PTCA percutaneous transluminal coronary angioplasty
  • vascular smooth muscle cells mainly composed of vascular smooth muscle cells.
  • Intimal hyperplasia resulting from proliferation of vascular smooth muscle cells, migration to the intima, matrix deposition, etc. is also a major cause of atherosclerotic disease, hypertension, ischemic heart disease, and cerebrovascular disease. It has become.
  • vascular stenosis after transplantation of organs such as the heart, liver, kidney, and blood vessels also involves the proliferation of vascular smooth muscle cells.
  • Anti-thrombotic drugs and vasodilators are mainly used as therapeutic agents for angina pectoris and myocardial infarction.
  • PTC A Restenosis after PTCA and narrowing of blood vessel lumen caused by arteriosclerosis and elasticity of blood vessels.
  • the triterpenes according to the present invention are generally pentacyclic compounds consisting of six isoprene units and having a basic carbon number of 30, but are transferred, oxidized, desorbed or alkylated during the biosynthesis process to obtain carbon atoms. Is also included. These effects are generally known to include anti-inflammatory effects and anti-carcinogenic promoter effects (Journal of the Japan Oil Chemists' Society, 49, 571, 2000). In particular, peroleic acid and oleanolic acid are known to have an anti-hyperlipidemic effect, and it is also known that persolic acid has an effect on atherosclerosis associated with hyperlipidemia.
  • the present invention suppresses vascular smooth muscle cell proliferation and migration, and prevents and / or treats cell proliferative vascular lesions such as intimal hyperplasia and arteriosclerosis, and vascular disorders such as arteriosclerosis and restenosis after PTCA. Therefore, it is an object of the present invention to provide a food and drink for vascular disorders having a very excellent effect on them.
  • the present inventors have conducted intensive studies to achieve the above object, and as a result, a compound selected from the group consisting of pentacyclic triterbenes, their physiologically acceptable salts, and their derivatives, Artery caused by vascular smooth muscle cell proliferation and / or vascular smooth muscle cell migration due to smooth muscle cell proliferation inhibitory effect, vascular smooth muscle cell migration inhibitory effect, anti-cell proliferative vascular lesion effect, anti-vascular disorder disease effect, etc.
  • Completed the present invention by finding that it has excellent preventive and / or therapeutic effects on cell proliferative vascular lesions such as sclerosis and intimal hyperplasia, and vascular disorders such as arteriosclerosis and restenosis after PTCA. It has come.
  • the present invention relates to a food and beverage for suppressing vascular smooth muscle cell proliferation, comprising as an active ingredient a compound selected from the group consisting of pentacyclic triterpenes, their physiologically acceptable salts, and their derivatives
  • the present invention relates to a food and drink for inhibiting vascular smooth muscle cell migration, which comprises, as an active ingredient, a compound selected from the group consisting of pentacyclic triterpenes, their physiologically acceptable salts and their derivatives.
  • the present invention also relates to a food and drink for an anti-cell proliferative vascular lesion, comprising as an active ingredient a compound selected from the group consisting of pentacyclic triterpenes, their physiologically acceptable salts and their derivatives.
  • the cell proliferative vascular lesion is a vascular smooth muscle cell
  • the present invention relates to a food and drink for anti-cell proliferative vascular lesions caused by proliferation and / or vascular smooth muscle cell migration,
  • the present invention relates to a food and drink for anti-arterial sclerosis wherein the cell proliferative vascular lesion is arteriosclerosis.
  • the present invention relates to a food and drink for vascular disorders containing a compound selected from the group consisting of pentacyclic triterpenes, physiologically acceptable salts thereof and derivatives thereof as an active ingredient
  • the present invention relates to a food and drink for a vascular disorder disease in which the vascular disorder disease is caused by a cell proliferative vascular lesion, preferably, to a food and beverage for an anti-arteriosclerosis in which the vascular disorder disease is arteriosclerosis. It relates to anti-restenotic food and drink after PTCA, which is restenosis after PTCA.
  • the present invention also relates to a food and drink for vascular vascular disorders, comprising an extract obtained by treating a defatted olive with an ethanol solution.
  • the present invention also provides a vascular smooth muscle cell proliferation or vascular smooth muscle cell containing, as an active ingredient, a compound selected from the group consisting of pentacyclic triterpenes, physiologically acceptable salts thereof, and derivatives thereof.
  • the present invention relates to a food or drink for preventing or treating a disease associated with a pathological condition or pathology involved.
  • the present invention also provides an intimal hyperplasia, arteriosclerosis, and cell proliferation containing, as an active ingredient, a compound selected from the group consisting of pentagonal triterpenes, a physiologically acceptable salt thereof, and a derivative thereof.
  • the present invention relates to a food for preventing or treating post-restenosis, myocardial infarction, angina pectoris, ischemic heart disease, cerebral infarction, stroke or cerebrovascular disease.
  • the present invention also relates to the use of a compound selected from the group consisting of a pentacyclic triterpene, a physiologically acceptable salt thereof and a derivative thereof for producing a food or drink for a vascular disorder.
  • the present invention also relates to a raw material for food and drink for vascular disorders, which comprises a compound selected from the group consisting of pentacyclic triterpenes, physiologically acceptable salts thereof, and derivatives thereof.
  • the present invention also relates to a raw material for food and drink for vascular disorders, which comprises an extract obtained by treating a defatted olive with an ethanol solution.
  • the present invention relates to a food and drink for inhibiting vascular smooth muscle cell proliferation, which comprises, as an active ingredient, a compound selected from the group consisting of pentacyclic triterpenes, their physiologically acceptable salts, and their derivatives.
  • pentagonal triterpenes preferred are oleane-based triterpenes, ursan-based triterpenes, and luban-based triterpenes.
  • maslinic acid, erythrodiol, persolic acid, baiole, benulinic acid or benline is preferred.
  • maslinic acid, erythrodiol and ebaol are preferred.
  • Particularly preferred is maslinic acid.
  • the present invention relates to a food and drink for inhibiting vascular smooth muscle cell migration, which comprises, as an active ingredient, a compound selected from the group consisting of pentagonal triterpenes, their physiologically acceptable salts and their derivatives.
  • pentagonal triterpenes preferred are oleane-based triterpenes, ursan-based triterpenes, and luban-based triterpenes.
  • maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, and berylin are preferred.
  • maslinic acid, erythrodiol, and benzoyl are preferred.
  • Particularly preferred is maslinic acid.
  • These substances are pentagonal compounds among triterpenes composed of six isoprene units, and are a group of substances that are abundant in various plants in nature. These can be obtained by extracting them from plants naturally, and some of them are artificially synthesized and some are already sold as reagents. Can be used appropriately. Those extracted from natural raw materials are preferred.
  • the term "containing as an active ingredient” means that it is contained to such an extent that it exhibits the effect of inhibiting vascular smooth muscle cell proliferation and the effect of inhibiting Z or vascular smooth muscle cell migration, but the content is not particularly limited. It may be adjusted appropriately according to the frequency of intake, the amount of intake, and the purpose of use. Although not particularly limited, for example, 0.0001% by mass or more, preferably 0.0001 to 99.99% by mass, more preferably 0.001 to 99.99% by mass, and still more preferably 0.005 to 99.99% by mass. %, More preferably 0.01 to 99.99% by mass, more preferably 0.05 to 99.99% by mass, more preferably 0.1 to 99.99% by mass, and still more preferably 0.5 to 99.99% by mass. The content is 99% by mass, more preferably 1 to 99.99% by mass.
  • the present invention also relates to a food and drink for an anti-cell proliferative vascular lesion, comprising as an active ingredient a compound selected from the group consisting of pentacyclic triterpenes, their physiologically acceptable salts and their derivatives.
  • the present invention relates to a food or beverage for an anti-cell proliferative vascular lesion in which the cell-proliferative vascular lesion is caused by vascular smooth muscle cell proliferation and / or vascular smooth muscle cell migration.
  • the present invention relates to an anti-inner monthly hypertrophic food or drink, and preferably to an anti-arteriosclerotic food or drink wherein the cell proliferative vascular lesion is arteriosclerosis.
  • oleane-based triterpenes preferred are oleane-based triterpenes, ursan-based triterpenes, and lupine-based triterpenes.
  • maslinic acid, erythrodiol and ebaol are preferred.
  • maslinic acid have an anti-cell proliferative vascular pathological effect, for example an intimal hyperplasia inhibitory effect and / or an anti-atherosclerotic effect, and these effects can be evaluated in animal tests.
  • containing as an active ingredient means that it is contained to such an extent that it exerts an anti-cell proliferative vascular lesion effect, for example, an intimal thinning effect and / or an anti-atherosclerotic effect.
  • an anti-cell proliferative vascular lesion effect for example, an intimal thinning effect and / or an anti-atherosclerotic effect.
  • 0.0001% by mass or more preferably 0.0001 to 99.99% by mass, more preferably 0.001 to 99.99% by mass, and still more preferably 0.005 to 99.99% by mass.
  • % More preferably 0.01 to 99.99% by mass, more preferably 0.05 to 99.9% by mass, more preferably 0.1 to 99.99% by mass, and still more preferably 0.5 to 99% by mass. 99 mass%, more preferably 1 to 99.99 mass%.
  • the present invention relates to a food or drink for vascular disorders, comprising as an active ingredient a compound selected from the group consisting of pentagonal triterpenes, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a food and drink for a blood vessel disorder in which the vascular disorder is caused by a cell proliferative vascular lesion. Relates to anti-restenotic food and drink after PTCA, which is restenosis after PTCA.
  • pentacyclic triterpenes preferred are oleane-based triterpenes, ursan-based triterpenes, and lupine-based triterpenes.
  • maslinic acid erythrodiol, persolic acid, baol, berylic acid or beryline is preferred.
  • maslinic acid, erythrodiol and ebaol are preferred.
  • maslinic acid are preferred.
  • anti-vascular disease effects such as anti-atherosclerotic and / or anti-restenotic effects. And these effects can be evaluated in animal and clinical test methods.
  • the term "containing as an active ingredient” means that the compound is contained to such an extent that it exhibits an anti-vascular disorder disease effect, for example, an anti-arteriosclerosis effect and / or an anti-restenosis effect. Its content is not particularly limited.
  • 0.0001% by mass or more preferably 0.0001 to 99.99% by mass, more preferably 0.001 to 99.99% by mass, and still more preferably 0.005 to 99.99% by mass.
  • 99% by mass more preferably 0.01 to 99.99% by mass, still more preferably 0.05 to 99.99% by mass, further preferably 0.1 to 99.99% by mass, more preferably 0.5 to 9% by mass. 99.99% by mass, more preferably 1 to 99.99% by mass.
  • the present invention relates to a food and / or beverage for inhibiting vascular smooth muscle cell proliferation, comprising a compound selected from the group consisting of pentacyclic triterpenes, physiologically acceptable salts thereof and derivatives thereof as an active ingredient.
  • Food and drink for muscle migration suppression and / or food for anti-intimal thickening Food and drink for anti-cell proliferative vascular lesions such as food and drink for anti-arteriosclerosis and / or food and drink for anti-atherosclerosis
  • Food and drink for vascular disorders such as anti-restenosis food and drink.
  • These substances are a kind of triterpenes and are pentacyclic compounds consisting of six isoprene units, and can be obtained from natural plants or artificially, and commercially available products are also suitable. Can be used for Those extracted from natural raw materials are preferred.
  • the term “containing as an active ingredient” as used herein means that the compound is contained to such an extent that the effect of each purpose is exhibited.
  • the present invention also provides a vascular smooth muscle cell proliferation or vascular smooth muscle cell containing, as an active ingredient, a compound selected from the group consisting of pentacyclic triterpenes, physiologically acceptable salts thereof, and derivatives thereof.
  • the present invention relates to a food or drink for preventing or treating a disease associated with a pathological condition or pathology involved.
  • pentacyclic triterpenes preferred are oleane-based triterpenes, ursan-based triterpenes, and luban-based triterpenes.
  • maslinic acid, erythrodiol, persolic acid, baol, veric acid or verulin is preferable.
  • maslinic acid, erythrodiol, and benzoyl are preferred.
  • Particularly preferred is maslinic acid.
  • the present invention also provides an intima moon, arteriosclerosis, cell containing a compound selected from the group consisting of pentagonal triterpenes, physiologically acceptable salts thereof and derivatives thereof as an active ingredient.
  • Proliferative vascular lesions coronary atherosclerosis, abdominal aortic sclerosis, obstructive atherosclerosis, renal arteriosclerosis, carotid atherosclerosis, fundus atherosclerosis, cerebral atherosclerosis, arteriosclerosis, percutaneous coronary angioplasty
  • the present invention relates to a food or drink for preventing or treating post-operative restenosis, myocardial infarction, angina pectoris, ischemic heart disease, cerebral infarction, stroke or cerebrovascular disease.
  • oleane-based triterpenes preferred are oleane-based triterpenes, ursan-based triterpenes, and lupine-based triterpenes.
  • maslinic acid, erythrodiol, persolic acid, baol, berylic acid or berylin is preferred.
  • maslinic acid, erythrodiol and ebaol are preferred. More particularly, maslinic acid is preferred.
  • the present invention also relates to a raw material for food and drink for vascular disorders, which comprises a compound selected from the group consisting of pentacyclic triterpenes, physiologically acceptable salts thereof, and derivatives thereof.
  • pentagonal triterpenes preferred are oleane-based triterpenes, persane-based triterpenes, and lupine-based triterpenes.
  • maslinic acid, erythrodiol, persolic acid, baol, veric acid or verin is preferable.
  • maslinic acid, erythrodiol and ebaol are preferable.
  • Particularly preferred is maslinic acid.
  • the physiologically acceptable salt is, in particular, a salt derived from the carboxyl group of a pentacyclic triterpene acid (partial structure: -C00X; X represents any anionic substance). Also included are those originally contained in the isolates from natural sources in the invention. In the present invention, it is particularly limited as long as it is a salt usually used in foods and drinks or pharmaceutical compositions. Not determined.
  • alkali metal salts such as sodium, potassium, lithium, etc.
  • alkaline earth metal salts such as calcium, magnesium, potassium, lithium, zinc, etc.
  • ammonium methylamine, dimethylamine, trimethylamine, ethylamine, methylamine, triethylamine
  • Alkylamine salts such as propylamine, butylamine, tetrabutylamine, pentylamine and hexylamine, ethanolamine, diethanolamine, triethanolamine, propanolamine, dipropanolamine, isopropanolamine, diisopropanolamine, etc.
  • organic amine salts such as cananolamine salt, piperazine and piperidine, and salts such as 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.In general, these salts are more water-soluble than their pentacyclic triterpenes. In the present invention, it is particularly preferable when applied to water-based foods and drinks for vascular disorders.
  • 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 group A derivative having an alkoxy group, a derivative having an alkoxymethyl group, or a glycoside for example, a derivative having an alcohol ester group, a fatty acid ester group A derivative having an alkoxy group, a derivative having an alkoxymethyl group, or a glycoside.
  • 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 derived from maslinic acid, erythrodiol, persolic acid, ⁇ ⁇ Since it shows more lipophilicity than baol, berylic acid, and beverin, in the present invention, it is particularly preferable when applied to oil-based foods and drinks for vascular disorders, etc. It is more soluble in water than the pentacyclic triterpenes from which it is derived, and is therefore particularly preferable in the present invention when it is applied to foods and drinks for water-based vascular disorders. Some of these derivatives exist in nature, and are artificially formed as described above. Can be obtained. In addition, the derivatives of the present invention can be derivatized again and their salts can be used.
  • maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid and verin into the form of a suitable physiologically acceptable salt or derivative, water solubility or oil solubility can be improved.
  • a product having improved handling properties, quality, a vascular smooth muscle cell proliferation inhibitory effect, a vascular smooth muscle cell migration inhibitory effect, and the like can be provided.
  • 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: one 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 is, in particular,
  • the fatty acid ester group indicates a functional group formed as a result of a dehydration reaction between a general hydroxyl group and a fatty acid (partial structure: one 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, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, bivalic acid, caproic acid, caprylic acid, capric acid, pudecanoic acid, lauric acid , Myristic acid, palmitic acid, no remitrein Acid, stearic acid, oleic acid, elaidic acid, pacsenic acid, linoleic acid, linoleic acid, linolenic acid, arlinolenic acid, arachidic acid, arachidonic acid, eicosapenenoic acid, behenic acid, docosahexaenoic acid, lignoserin Acids, serotinic acid, montanic acid, melicic acid and the like.
  • the alkoxy group indicates a functional group formed as a result of a general dehydration reaction between a 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 alcohols used at this time.
  • derivatives formed from ethanol, triethylsilyl alcohol, methanol, n-propanol, isopropanol or trimethylsilyl alcohol are preferred.
  • an 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 is any hydrocarbon-based functional group) Is shown.). That is, the derivative having an alkoxymethyl group of the pentacyclic triterpene in the present invention particularly refers to a derivative that can be formed from the hydroxymethyl group and an alcohol.
  • alcohols for example, methanol, ethanol, n-propanol, isopropanol, aryl alcohol, n-butanol, sec-butanol, tert-butanol, ethylene glycol, trimethylsilyl alcohol, triethylsilyl alcohol, Examples include phenol, benzyl alcohol, and saccharides. Of these, derivatives formed from ethanol, triethylsilyl alcohol, methanol, n-propanol, isopropanol or 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 are no particular restrictions on the saccharide at this time, and examples thereof include glucose, mannose, galactose, fructose, xylose, arabinose, fucose, rhamnose, dalcosamine, galactosamine, glucuronic acid, and the like. Good. These glycosides may be monosaccharides or oligosaccharides in various combinations of disaccharides or more. Some of these usually occur naturally and are known by the generic term saponin, but any of these may be used in the present invention.
  • pentacyclic triterpenes and the like in the present invention are as described above, particularly from the aspect of high anti-arterial hardening effect, oleanean triterpenes, ursan triterpenes, ruban triterpenes, and those thereof Physiologically acceptable salts or their derivatives are preferred.
  • Oleanane triterpenes are represented by the general formula (I)
  • ursan triterpenes are represented by the general formula (II)
  • lupine triterpenes are represented by the general formula (III).
  • the functional groups in each formula are the same as above,
  • R 2 represent a hydrogen atom (-H), a hydroxyl group (-OH), an alkoxy group (-10 R), and an alcohol ester group (-OCOR)
  • R 3 is a methyl group (-CH3) , Hydroxymethyl group (one CH2 OH), alkoxymethyl group (one CH2OR), carboxyl group (one COOH), fatty acid ester group (one COOR), carboxylate
  • R1 represents a hydrogen atom (-H), a hydroxyl group (-OH), an alkoxy group (-OR), an alcohol ester group (-OCOR); 2 is a methyl group (-CH3), a hydroxymethyl group (-CH20H), alkoxymethyl group (-CH2OR), carboxyl group (-C00H), fatty acid ester group (-C00R carboxylate (-CO OX). )
  • R 1 represents a hydrogen atom (—H), a hydroxyl group (—OH), an alkoxy group (—0R), an alcohol ester group (one OCOR), and R 2 represents a methyl group (one CH 3)
  • examples of the oleane-based triterpenes include maslinic acid, oleanolic acid, erythrodiol, monoamyline, hederagenin, glycyrrhetinic acid, and the like. Monohydric acid, eubaol, sodium amylin, quinovonic acid, taraxasterol, sodium hydroxyduronic acid, and the like; and lupine triterpenes, such as berylic acid, behline, and ruol. .
  • the physiologically acceptable salts and derivatives thereof are the same as described above.
  • an oleanean triterpene When a physiologically acceptable salt thereof or a derivative thereof is used, an oleanean triterpene, an ursan triterpene, a lupine triterpene and a physiologically acceptable salt thereof, or
  • the origin of the derivative is not limited, and any of natural derivatives, artificially synthesized derivatives, and commercial products can be used. It is preferable to use a natural product in consideration of the fact that it is a product.
  • the oleane triterpenes (1), the ursan triterpenes (11), the lupine triterpenes (III), and their physiologically acceptable triterpenes (III) Or their derivatives are preferred, but in view of the strength of the anti-atherogenic effect, oleanane-based triterpenes are more preferably maslin tori and erythrodiol, and ursan-based triterpenes are preferably persolic acid and baobaol, and lupine is preferred.
  • beryric acid and beryline are preferred, and of course, their physiologically acceptable salts or their derivatives are preferred.
  • Both maslinic acid and erythrodiol are one type of oleane-based triterpenes, and are substances known to be present in various plants.
  • the physiologically acceptable salts and derivatives thereof are the same as described above.
  • maslinic acid, erythrodiol, a physiologically acceptable salt thereof, or a derivative thereof is used in the food and drink for a vascular disorder disease of the present invention, the origin of these substances is not limited, Any of those obtained from nature, artificially synthesized, commercially available products and the like can be used.
  • maslinic acid and / or a physiologically acceptable salt thereof are most preferable in terms of high anti-atherosclerosis effect and stable supply.
  • Maslinic acid (mas 1 inicacid) is a kind of an oleanan-based triterpene and has a structure represented by the chemical formula (IV), and is known to have an anti-inflammatory effect and an anti-histamine effect. In nature, it is known to be present in olive, hop, heart, pomegranate, foliage, sage, jujube, and the like.
  • the origin of maslinic acid, its physiologically acceptable salts and derivatives is not limited, and any of those obtained from nature, artificially synthesized, and commercially available products Can also be used, but taking oral use into account, for example, olive, hop, Preference is given to those obtained from nature, such as pomegranate, pomegranate, chickpea, sage, and jujube, and particularly maslinic acid and / or its physiologically acceptable salts obtained from olive oil are not sufficient in terms of raw material supply and content. Is very preferred. These raw materials, especially olive plants, can be obtained by extraction with water and / or an organic solvent, and further concentrated and purified to obtain high-concentration maslinic acid and / or its physiologically high concentration. An acceptable salt can be obtained easily and in large quantities.
  • “olive” means olive plant and / or olive oil and / or a product obtained in the olive oil production process.
  • the physiologically acceptable salts and derivatives of maslinic acid are the same as described above. That is, the physiologically acceptable salt is a salt derived from 1 C ⁇ 0 H in the chemical formula (IV), and the type of the salt may be any of those usually used in foods and drinks or pharmaceutical compositions. There is no particular limitation. Specifically, for example, as a 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.
  • maslinic acid methyl ester examples include, for example, maslinic acid methyl ester, maslinic acid ethyl ester, maslinic acid n-propyl ester, maslinic acid isoprovir ester, maslinic acid n —Butyl ester, trimethylsilyl maslinate, triethylsilyl maslinate, maslinic acid 1 /? — D-glucoviranosyl ester, maslinic acid 1 /?
  • Triethylsilyl acid ester Triethylsilyl acid ester, 3-0-acetyl-maslinic acid, 2-0-acetyl-maslinic acid, 21-0-triethylsilylmonomaslinic acid, 3-0-stearoyl-massic acid and 2-0-stearoyl-mass Phosphoric acid is preferred.
  • a derivative in which only one group is derivatized has been described, but it is needless to say that a derivative in which two or more groups capable of being derived and of which type are derivatized may be used.
  • maslinic acid or 2,3-0-diacetyl, 2,3-0-ditriethylsilyl and 2,3-distearoyl of the above-mentioned preferable maslinic acid esters are preferred.
  • glycosides are listed as the glycosides, but naturally, disaccharides or more oligosaccharides selected from the group consisting of various saccharides may be used.
  • Erythrodiol is a kind of oleanane-based triterpene, which has a structure similar to the chemical formula (V), and has an anti-inflammatory effect (Plant a. Med. VOL. 61, No. 2, 182-185 19 95). In nature, it is known to be present in olive, sunflower, calendula, gum arabic, kodoxitan, nagaka konoki, and the like. In the food and drink for vascular disorders according to the present invention, the origin of erythrodiol or a derivative thereof is not limited, and any of those obtained from nature, artificially synthesized, and commercially available products may be used.
  • physiologically acceptable salts and derivatives of erythrodiol are the same as described above.
  • the derivative is not limited to the following, but, for example, assuming that any one of the derivatives is a derivative, 3-0-acetyl-erythrodiol, 3-0-pulp-pioneluerythrodiol, 3-0-butyryl-erythrodiol, 3-0-norelylerythrodiol, 3-0-capryl-erythrodiol, 3-0-lauryl-erythrodiol, 3-0-myristyl-erythrodiol, 3-0- Noremicil monoerythrodiol, 3-0—palmi toreyl erythrodiol, 3-0—stearyl erythrodiol, 3-0—stearoyl erythrodiol, 3_0—oleyl erythrodiol, 3-0—bakseni Luery trodiol, 3-0—LinoleiLu erythrodiol, 3-0—Linolenyl-erythro
  • D Glucobiranosyl-erythrodiol, 3-0—? —! — Galactopyranosyl-erythrodiol, 3-0 — /? — D—Glucuronoviranosyl-erythrodiol, 28—0— ? —D—Glucobiranosyl-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.
  • a derivative in which only one group is derivatized has been described, but of course, a derivative in which two or more groups of which positions and types can be derived are derivatized may be used.
  • 3,28-0-diacetyl-erythrodiol is preferred.
  • glycosides are listed as glycosides, naturally, disaccharides or more oligosaccharides selected from the group consisting of various saccharides may be used.
  • Ursolic acid and ebaol are all a kind of ursan triterpenes and are known to be present in various plants. In addition, these physiological The salts and derivatives that are chemically acceptable are the same as described above.
  • the origin of these substances is not limited. Any of natural products, artificially synthesized products, and commercially available products can be used. However, in consideration of oral use, it is preferable to use natural products.
  • Persolic acid (u ⁇ ⁇ so 1 ic acid) is a kind of ursane triterpene, a compound having a structure represented by the chemical formula (VI), and has been used as an anti-inflammatory, anti-atherosclerotic, It is known to have a diabetic effect, an antihyperlipidemic effect (Jie Liu, Journal of Ethnopharmaco 1 o, 49, 57-68, 1995) and the like. Naturally, it is known to be widely distributed in fruits and leaves such as apples, cherries, and perilla. In the food and drink for vascular diseases of the present invention, the origin of persolic acid, a physiologically acceptable salt thereof, or a derivative thereof is not limited, and it may be obtained from nature or artificially synthesized. Any of these can be used, but commercially available ones are preferred, but in consideration of oral use, those obtained from natural sources such as apples, cherries, and peony are preferred.
  • physiologically acceptable salts and derivatives of persolic acid are the same as described above.
  • physiologically acceptable salts are not limited to the following, but, for example, as salts of persolic acid, sodium persoleate, potassium ursorate, ammonium persoleate, dimethyl ammonium persoleate, Examples include calcium ursolic acid and magnesium ursolic acid.
  • Examples of the derivatives of ursolic acid include, for example, those in which any one of the derivatives is derivatized, such as methyl persolic acid, ethyl ethyl ursolic acid, n-propyl ursolic acid, and isopropyl persolic acid N-butyl persulfate, trimethylsilyl persoleate, triethylsilyl ursoleate, mono-persullic acid /?-D-glucoviranosyl ester, ursolic acid-/?-D-galactoviranosi Ester, 3-0-acetyl-persolic acid, 3-0-propionyl-ursolic acid, 3-0-butyryl-ursolic acid, 3-0-valeryl-ursolic acid, 3-0-capryl Persolic acid, 3-0-lauryl-ursolic acid, 3-0-myristyl-ursolic acid, 3-0—palmityl-perso Oleic acid
  • ⁇ Paol (uvaol) is a kind of ursan-based triterpene and has a structure similar to the chemical formula (VII). It has an anti-inflammatory effect (Plant a. Med. VOL. 61, No. 2, 182). -185 1995), and glycerol phosphate dehydrogenase inhibitory effect (JP-A-9-67249). In nature, it is known to be found in oribu, ⁇ aurushi, sage, gum arabic, rypte, etc. In the food and drink for vascular disorders of the present invention, the origin of Baobal or a derivative thereof is not limited, and any of those obtained from nature, artificially synthesized, and commercially available products can be used. However, in consideration of oral use, those obtained from natural sources such as oribu, oak, sage, gum arabic and capute are preferred. In particular, olive is preferred, and specifically, those obtained from the product obtained in the olive plant and / or olive oil production process.
  • the derivative is not limited to the following.
  • any one of the derivatives is inducted, 3-0-acetyl-baobaol, 3-0-propionyl-baobal, 3-0-butylic Roubaol, 3-0—Valeryl—Baobaol, 3—0—Power prill—Baobal, 3—0 Laurilubaobaol, 3—0 One millistill—Baobal, 3—0—Palmityl—Baobaol, 3—0 —Palmi Torail-Baobaul, 3 — 0 — Stearyl Baobaul, 3 — 0 — Steer mouth Virgin Baor, 3 — 0 — Oreira Baobaul, 3 — 0 — Baxenru Baol, 3 — 0— Linoleurium Baol, 3-0
  • 2 8-0 Stearoyl—Baobaol, 2 8—0—Vorreil Baol, 2 8—0—Baxenyl Baobal, 2 8—0—Linoleil—Baobal, 2 8—0—Linolenyl—Baol , 2 8-0-arachidyl-l-baol, 28-0-arachidonil-l-baol, 28-0-behyl-l-baol, 3-0-methyl-l-baol, 3-0-ethyl-l-baol, 3 _ 0—t monobutyl—divinyl, 3-0—triethylsilyl—dithiol, 28—0—methyl—dithiol, 28—diethyl—diol, 28—0—t—butyl Baol, 2 8—0—triethylsilyl— ⁇ baol, 3—0 — — /
  • Bepulinic acid and Bepulin are all 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.
  • berlinic acid, perrin, their physiologically acceptable salts, or their derivatives when used, the origin of these substances is not limited, Any of natural products, artificially synthesized products, and commercially available products can be used, but natural products are preferably used in consideration of oral use.
  • Betulinic acid (bet ⁇ i 1 inicacid) is a kind of lupine triterpene and has a structure like chemical formula (VIII). Its effects have been anticancer, anti-inflammatory and wound healing. Effects (Japanese Patent Publication No. Hei 21-6632), alcohol absorption suppression effect (Japanese Patent Application Laid-Open No. Hei 7-53338), hair growth promoting effect (Japanese Patent Application Laid-Open No. Heisei 9-11577139), etc.
  • berylic acid its physiologically acceptable salts and derivatives are the same as described above.
  • physiologically acceptable salts are not limited to the following.
  • examples of the salts of beryric acid include sodium diphosphate, potassium diphosphate, ammonium perphosphate, dimethyl ammonium perate, Examples thereof include calcium perphosphate and magnesium perphosphate. Of these, sodium perphosphate and potassium perphosphate are preferred.
  • derivatives of berylic acid include those in which any one of the derivatives is derivatized, such as methyl berylate, ethyl berylate, n-propyl ester of berylic acid, isopropyl berylate, N-butyl ester of veric acid, trimethylsilyl ester of veritic acid, triethylsilyl ester of veritic acid, mono- / mono-peroxy-D-glucoviranosyl ester, mono- / mono-periodic of veric-acid
  • D-Glucobiranosyl monophosphate 3-0—5—D-Galactopyranosyl monophosphate, 3-0- ⁇ -D-glu Chronobiranosyl-veperic acid and the like.
  • ethyl phosphate is preferred.
  • only one derivative has been derivatized. However, of course, two or more of the derivatives having derivable positions and types may be derivatized.
  • only glycosides are listed as monosaccharides, but naturally, disaccharides or more oligosaccharides selected from the group consisting of various saccharides may be used.
  • Betuline (betu 1 in) is a kind of lupine triterpene and has a structure similar to the chemical formula (IX).
  • Glycerophosphate dehydrogenase inhibitory effect Japanese Patent Application Laid-Open No. 9-67249
  • lipase inhibitory effect Japanese Patent Application Laid-Open No. 10-2653228
  • liver disease preventive effect Japanese Patent Application Laid-open No. 2 7 5
  • it is known to be present on the bark of birch and the like.
  • the origin of beverin 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. However, in consideration of oral use, those obtained from natural sources such as birch bark are preferable.
  • the physiologically acceptable salts and derivatives of beverin are the same as described above.
  • the derivative is not limited to the following.
  • any one of the derivatives is inducted, 3-0-acetyl-verperin, 3-0-propionyluperin, 3-0-butylylperine Perrin, 3—0—Valeryl perveline, 3—0—Capryluperine, 3—0—Lauriluperine, 3—0—Myristyl perveline, 3—0—Noremicil perveline, 3 _ 0 _Palmi Toray Luberin, 3-0—Stearyl monoberin, 3-0—Stearoyluberin, 3-0—Oleyluberin, 3-0—Baxenruberin, 3-0—Linolyl Perrin, 3-0—Linolenyl-verin, 3-0—Arachidyl monolin, 3-0—Arachidonyl monolin, 3—Ninyl veruline, 28—0—Acetyl-verin, 2 8— 0—propione Berulin,
  • the present invention relates to a food and drink for inhibiting vascular smooth muscle cell proliferation, comprising as an active ingredient a compound selected from the group consisting of the above-mentioned pentagonal triterpenes, their physiologically acceptable salts and their derivatives.
  • containing as an active ingredient means containing the vascular smooth muscle cell to such an extent that the cell growth inhibitory effect is exhibited.
  • the vascular smooth muscle cell proliferation inhibitory effect indicates that the vascular smooth muscle cells that have invaded the atherosclerotic lesions are inhibited from growing in the atherosclerotic lesions. It can be expected to prevent it from forming in the intima of the blood vessel and to prevent the existing atherosclerotic lesions from further hypertrophy or to reduce them.
  • the food and drink for inhibiting vascular smooth muscle cell proliferation of the present invention is used for prevention and / or treatment of arteriosclerosis and the like. Preventive use refers to inhibiting the proliferation of vascular smooth muscle cells that have migrated to the intima and preventing atherosclerosis from occurring.
  • the present invention also relates to a pathology involving vascular smooth muscle cell proliferation, which comprises as an active ingredient a compound selected from the group consisting of pentacyclic triterpenes, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a food or drink for preventing or treating a disease associated with a disease state.
  • the method used for evaluating the vascular smooth muscle cell proliferation inhibitory effect in the present invention is a known method for screening anti-atherosclerotic drugs in vitro (JP-A-5-56769), and screening is easy. It is characterized by the fact that rapid and massive animal sacrifice can be avoided.
  • the use of a reagent that generates a fluorescent substance by the oxidation-reduction ability of cultured vascular smooth muscle cells is used, and the amount of the fluorescent substance is determined based on the intensity of the fluorescence intensity to examine the presence or absence of the growth inhibitory effect. I have.
  • vascular smooth muscle cell proliferation inhibitory effect of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the present invention is shown by a test method using vascular smooth muscle cells.
  • vascular smooth muscle cells present in the media of the arterial wall repeatedly contract and relax to regulate blood flow, and are structurally rich in fibrous components including hyactin.
  • the vascular smooth muscle cells targeted in the present invention are phenotypes converted to a synthetic form by stimulation of smooth muscle growth factor or the like, and this evening loses contractile ability due to coarse fiber components.
  • the vascular smooth muscle cells used in the present invention are a cultured vascular smooth muscle cell line derived from rat aorta, and when cultured normally, have a multiplication time of 25 hours and a growth capacity of 25 hours. A uniform monolayer is formed on the top.
  • a substance having an inhibitory effect on vascular smooth muscle cell proliferation is present in this culture system, the proliferation of vascular smooth muscle cells is suppressed, and the redox ability of the cells is relatively suppressed, thereby producing a fluorescent substance. And the fluorescence intensity decreases. From this relative degree of fluorescence intensity, the vascular smooth muscle cell proliferation inhibitory effect can be estimated.
  • the pentacyclic triterpenes, the physiologically acceptable salts thereof and the derivatives thereof according to the present invention show the vascular smooth muscle cell growth inhibitory effect by the known anti-atherosclerotic food and drink.
  • a certain tocopherol for example, about 10 to 14 times for maslinic acid, about 6 to 10 times for maslinic acid salt, about 10 to 14 times for erythrodiol, About 6 to 10 times for acid, about 4 to 8 times for baol, about 4 to 8 times for berlinic acid, about 4 to 8 times for phosphorus, about 6 to 10 times for maslin ethyl ester, acetyl Maslinic acid about 6 to 10 times, triethylsilylated maslinic acid about 4 to 8 times, stearylated maslinic acid phosphate about 6 to: L 0 times, acetylated erythrodiol about 4 to 8 times, persolic acid About 6 to 10 times for ethyl ester, It has a high vascular smooth muscle cell growth inhibitory effect of about 4 to 6 times for cetylated baioru, about 4 to 6 times for betyl phosphate, and about 4 to 6 times for
  • the pentagonal triterpenes, their physiologically acceptable salts, and their derivatives have an inhibitory effect on vascular smooth muscle cell migration. That is, the present invention more directly relates to a food and drink for inhibiting vascular smooth muscle cell migration, which comprises as an active ingredient a compound selected from the group consisting of pentacyclic triterpenes, their physiologically acceptable salts and their derivatives.
  • a food and drink for inhibiting vascular smooth muscle cell migration which comprises as an active ingredient a compound selected from the group consisting of pentacyclic triterpenes, their physiologically acceptable salts and their derivatives.
  • containing as an active ingredient means that it is contained to such an extent that its vascular smooth muscle cell migration inhibitory effect is exhibited.
  • the vascular smooth muscle migration inhibitory effect is caused by vascular injury, hyperlipidemia, etc.
  • Vascular smooth muscle cells derived from the media that acquired proliferative capacity from blood components that deviated from the normal value were transferred from the vascular media to the vascular intima or atherosclerotic lesions under the vascular endothelial cells according to the concentration gradient of the migration factor in the blood. And inhibits the migration (two migrations) of the blood vessels. As a result, it inhibits the migration of vascular smooth muscle cells to prevent the formation of atherosclerotic lesions, It can be expected that vascular smooth muscle cells will not migrate to the hardened lesions.
  • the food / drink for suppressing vascular smooth muscle cell migration of the present invention is intended to suppress the migration of vascular smooth muscle cells from the media to the intima, and to prevent the formation of arteriosclerotic foci. It is used to prevent the growth of hardened nests.
  • vascular smooth muscle cells are activated by a migration factor, and the number of cells that have migrated to a higher concentration of the migration factor is counted, and the presence or absence of a migration inhibitory effect is determined by comparing with the control group. ing.
  • the present invention also provides a compound which is effective for a compound selected from the group consisting of maslinic acid, erythrodiol, ursyl citrate, ebaol, vertulinic acid, berlin, their physiologically acceptable salts and their derivatives.
  • the present invention relates to a food or drink for preventing or treating a disease associated with a pathology or pathology involving vascular smooth muscle cell migration, which is contained as a component.
  • the inhibitory effect of pentacyclic triterpenes, physiologically acceptable salts thereof and derivatives thereof on vascular smooth muscle cell migration in the present invention is shown by a test method using vascular smooth muscle cells.
  • the vascular smooth muscle cell used in the present invention is a proliferative cultured vascular smooth muscle cell line derived from rat aorta. Cells migrate. On the other hand, if a substance having an inhibitory effect on vascular smooth muscle cell migration is present together with the migration factor, the number of cell migration is reduced. From this relative degree of cell number, the vascular smooth muscle cell migration inhibitory effect can be estimated.
  • the pentacyclic triterpenes, the physiologically acceptable salts thereof and the derivatives thereof according to the present invention show the vascular smooth muscle cell migration inhibitory effect
  • tocopherol for example, about 25 to 30 times for maslinic acid, about 25 to 30 times for maslinic acid salt, and about 25 to 30 times for ursolic acid 25 to 30 times, about 25 to 30 times for ethyl maslinate, about 25 to 30 times for acetylated maslinic acid, about 24 to 27 times for triethylsilylated maslinic acid
  • stearylated maslin Ethyl acid has a very high inhibitory effect on vascular smooth muscle cell migration, about 25- to 30-fold, and urzolyl ethyl ester about 24- to 27-fold.
  • a pentacyclic triterpene and a physiologically acceptable salt thereof, or a derivative thereof it is possible to enjoy a very strong vascular smooth muscle cell migration inhibitory effect. Particularly, they are very preferable because they also have a vascular smooth muscle cell proliferation inhibitory effect.
  • the present invention relates to a food and drink for an anti-cell proliferative vascular lesion containing, as an active ingredient, a compound selected from the group consisting of a pentacyclic triterpene, a physiologically acceptable salt thereof and a derivative thereof, as described above.
  • cell proliferative vascular lesion refers to a vascular tissue site in which intimal thickening or arteriosclerosis has occurred due to migration and abnormal proliferation of vascular smooth muscle cells, and includes coronary atherosclerosis, abdominal aortic sclerosis, and renal atherosclerosis. , Atherosclerotic lesions such as carotid atherosclerosis, fundus atherosclerosis, and cerebral atherosclerosis, and restenosis after PCTA.
  • the food and drink for anti-cell proliferative vascular lesions of the present invention are particularly effective for intimal hypertrophy and atherosclerosis due to vascular smooth muscle cell proliferation and Z or vascular smooth muscle cell migration. It has the effect of preventing and / or treating arteriosclerosis.
  • the present invention provides a compound selected from the group consisting of pentacyclic triterpenes, a physiologically acceptable salt thereof and a derivative thereof, wherein the cell proliferative vascular lesion is intimal thickening, as an active ingredient.
  • the present invention relates to anti-intimal thickening food and drink.
  • containing as an active ingredient means that the compound is contained to such an extent that the effect of suppressing intimal hyperplasia is exhibited.
  • the pentacyclic triterpenes, physiologically acceptable salts thereof, and the derivatives thereof according to the present invention show the inhibitory effect on intimal hyperplasia by an animal test method.
  • physically exfoliating the endothelial cells of the artery causes inflammation at the site, and vascular smooth muscle cells migrate and proliferate in the intima at the site, thereby thickening the intima.
  • administration of a substance having an intimal hyperplasia inhibitory effect to animals suppresses hypertrophy. From this degree of suppression, it is possible to estimate the effect of suppressing the hypertrophy of S.
  • the present invention provides an anti-arterial comprising as an active ingredient a compound selected from the group consisting of pentacyclic triterpenes, a physiologically acceptable salt thereof and a derivative thereof, wherein the cell proliferative vascular lesion is arteriosclerosis. It relates to food and drink for curing.
  • the anti-atherosclerotic food and drink of the present invention exerts an anti-atherosclerotic effect when administered orally, Z or parenterally.
  • the anti-atherosclerotic effect is intended to suppress the proliferation of vascular smooth muscle cells in the atherosclerotic lesion and / or to suppress the migration of proliferating vascular smooth muscle cells into the atherosclerotic lesion.
  • atherosclerosis is a condition in which arterial endothelial damage is triggered and transforms from contractile to proliferative. It is thought that vascular smooth muscle cells migrate from the media to the intima and proliferate in the intima, resulting in thickening of the vascular intima.
  • the anti-atherosclerotic food and drink of the present invention is a pentacyclic triterpene having a vascular smooth muscle cell proliferation inhibitory effect and / or a vascular smooth muscle cell migration inhibitory effect, and their physiologically acceptable Since it contains a compound selected from the group consisting of salts and their derivatives, it can be expected to minimize the occurrence of vascular diseases such as arteriosclerosis, ischemic heart disease, and cerebrovascular disease, which is very preferable.
  • the food and beverage for anti-arterial sclerosis of the present invention exerts its anti-atherosclerotic effect when ingested, improves or prevents ischemic heart disease and cerebrovascular disease, and prolongs the survival rate. It greatly contributes to In particular, an anti-atherosclerotic food or drink containing as an active ingredient a compound selected from the group consisting of maslinic acid, ursolic acid and their physiologically acceptable salts, or their derivatives, is effective for vascular smooth muscle cell proliferation. It has an inhibitory effect and an inhibitory effect on vascular smooth muscle cell migration and can be used as a powerful anti-atherosclerotic food and drink, and is very preferable.
  • the anti-arteriosclerotic effect of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the present invention is shown by a test method using animals. In other words, eating a high cholesterol diet for a long time causes arteriosclerosis in the aorta. In contrast, when a substance having an anti-atherosclerotic effect is administered to animals, arteriosclerosis of the aorta is suppressed. From this degree of suppression, the anti-arterial stiffening effect can be estimated.
  • the anti-atherosclerotic effect of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the present invention is compared with the control high cholesterol diet group, for example, , About 40 to 60% inhibition with maslinic acid, About 400% inhibition of maslinic acid salt, about 50% to 70% reduction of erythrodiol, about 400% reduction of ursolic acid, and about 350% reduction of ⁇ baol. ⁇ It can be seen that phosphoric acid has a high anti-atherosclerosis effect, about 25-45% inhibition, and Bellin about 25-45% inhibition. That is, by containing pentacyclic triternes, their physiologically acceptable salts, and their derivatives, a high anti-atherosclerotic effect can be enjoyed.
  • the present invention relates to a food or drink for vascular disorders containing a compound selected from the group consisting of pentacyclic triterpenes, physiologically acceptable salts thereof and derivatives thereof as an active ingredient.
  • the vascular disorder disease is a disease mainly caused by the above-mentioned cell proliferative vascular lesion, and is caused by proliferation of vascular smooth muscle cells and migration into the intima of blood vessels, such as arteriosclerosis and thickening of the intima. A disease caused as a result of a disorder.
  • arteriosclerosis such as coronary artery sclerosis, abdominal aortic sclerosis, obstructive arteriosclerosis, renal arteriosclerosis, cervical arteriosclerosis, fundus arteriosclerosis, cerebral arteriosclerosis, and restenosis after PTCA Stenosis
  • myocardial infarction ⁇ Ischemic heart disease such as angina, cerebral infarction ⁇ Cerebrovascular disease such as stroke.
  • the food and drink for a vascular disorder disease of the present invention have an effect on vascular smooth muscle cells involved in the occurrence of vascular disorders, and have an effect on arteriosclerosis due to the occurrence of a cell proliferative vascular lesion mainly composed of vascular smooth muscle cells and after PTCA.
  • Preventive effects include inhibiting the proliferation and / or migration of vascular smooth muscle cells to prevent the formation of atherosclerotic foci and intimal hyperplasia, as well as atherosclerosis and restenosis after PTCA. Shows to prevent vascular disorders.
  • the therapeutic effect is to suppress the proliferation and / or migration of vascular smooth muscle cells further, or to reduce the number of proliferated vascular smooth muscle cells rapidly, etc.
  • the present invention provides an anti-arterial comprising, as an active ingredient, a compound selected from the group consisting of pentacyclic triterpenes, a physiologically acceptable salt thereof, and a derivative thereof, wherein the vascular disorder is arteriosclerosis. It relates to food and drink for sclerosis.
  • arteriosclerosis is a comprehensive term for many diseases in which the arterial wall thickens and loses elasticity, and refers to systemic cardiovascular disorders.
  • the present invention relates to an anti-atherosclerosis food and drink comprising the above-mentioned substance as an active ingredient, having an effect on vascular smooth muscle cells involved in the formation of atherosclerotic foci.
  • foods and drinks for anti-atherosclerosis containing as an active ingredient a compound selected from the group consisting of maslinic acid, ursolic acid and their physiologically acceptable salts, or derivatives thereof, are useful for vascular smooth muscle cell proliferation. Since it has an inhibitory effect and an inhibitory effect on vascular smooth muscle cell migration, it can be used as a powerful anti-atherosclerosis food and drink, and is very preferable.
  • the present invention provides, as an active ingredient, a compound selected from the group consisting of a pentacyclic triterpine, a physiologically acceptable salt thereof, and a derivative thereof, wherein the vascular disorder is restenosis after PTCA.
  • a compound selected from the group consisting of a pentacyclic triterpine, a physiologically acceptable salt thereof, and a derivative thereof wherein the vascular disorder is restenosis after PTCA.
  • PTCA On anti-restenotic food and drink after PTCA.
  • the anti-restenotic food and drink of the present invention when taken orally, exhibits the aforementioned intimal hyperplasia suppressing effect.
  • the food and drink for anti-restenosis after PTCA of the present invention include pentacyclic triterpenes having an inhibitory effect on vascular smooth muscle cell proliferation and / or an inhibitory effect on vascular smooth muscle cell migration and the like.
  • ischemic heart disease due to restenosis after PTCA, which is very favorable. That is, the food and drink for anti-restenosis after PTCA of the present invention exerts its intimal hyperplasia-suppressing effect when ingested, and can improve or prevent ischemic heart disease and prolong the survival rate. It will greatly contribute.
  • an anti-restenotic food or drink containing as an active ingredient a compound selected from the group consisting of maslinic acid, persolic acid, and physiologically acceptable salts thereof, and derivatives thereof has a vascular smooth muscle cell growth inhibitory effect and Since it has a vascular smooth muscle cell migration inhibitory effect, it can be used as a powerful anti-restenotic food and drink, and is very preferable.
  • Pentacyclic triterpenes and their 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 generally fat-soluble, and are therefore oil-based or emulsified blood vessels. It can be suitably added to foods and drinks for disorders. 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 pentacyclic triterpenes generally show water solubility, they can be uniformly dissolved or dispersed in aqueous or emulsified foods and drinks for vascular disorders. It can be suitably blended by containing. In particular, drinks and the like are often commercialized in water-based or milk-based systems. In this case, it is preferable to use a pentacyclic triterpene as a physiologically acceptable salt or glycoside as necessary. It can be appropriately blended.
  • pentagonal triterpenes have a strong effect and can be used in a small amount of foods and drinks for vascular disorders, etc. Since it has the effect of inhibiting muscle cell proliferation and the effect of inhibiting vascular smooth muscle cell migration, it has the advantage of cost and has a margin to mix other components in terms of the mixing ratio. Function can be further enhanced, preferable.
  • the present invention enables production of foods and drinks, foods and drinks for anti-cell proliferative vascular lesions, foods and drinks for vascular disorders and the like.
  • the pentacyclic triterpenes in the present invention are known to exist as natural products in plants and the like, and most of them have a food test through those plants, and No adverse effects on living organisms unless ingested
  • the LD50 value is 200 Omg / kg of body weight or more, confirming that the safety is extremely high.
  • pentacyclic triterpenes having a vascular smooth muscle cell proliferation inhibitory effect, a vascular smooth muscle cell migration inhibitory effect, etc., their physiologically acceptable salts and their derivatives can be safely administered. Is shown.
  • the food and drink for inhibiting vascular smooth muscle cell proliferation of the present invention can obtain more favorable effects by ingesting continuously.
  • the amount of the compound selected from the group consisting of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the food and drink for inhibiting vascular smooth muscle cell proliferation of the present invention is generally specified. Not appropriate, considering the type of triterbene, the purpose of use (prevention or treatment), period of use, amount, age, sex, weight, etc. You just have to decide.
  • 0.0001 to 90% by mass more preferably 0.0001 to 80% by mass, further preferably 0.001 to 70% by mass, further preferably 0.01 to 65% by mass, More preferably, 0.1 to 60% by mass, more preferably, 0.2 to 55% by mass, more preferably, 0.4 to 50% by mass, further preferably, 0.6 to 45% by mass, more preferably, Is 0.8-40% by mass
  • the content is more preferably 1.0 to 35% by mass, and even more preferably 2.0 to 30% by mass. In any case, the higher the content, the stronger the effect. However, it is necessary to adjust the content in consideration of the purpose of use, period of use, amount, age, sex, weight, etc. of the target.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food and drink for inhibiting vascular smooth muscle cell proliferation in the present invention, preferably 0.000001 to 90% by mass, Preferably from 0.0001 to 80% by mass, more preferably from 0.001 to 70% by mass, more preferably from 0.01 to 65% by mass, more preferably from 0.1 to 60% by mass, further preferably from 0.2 to 55% by mass. %, More preferably 0.4 to 50% by mass, still more preferably 0.6 to 45% by mass, further preferably 0.8 to 40% by mass, more preferably 1.0 to 35% by mass, and still more preferably 2 to 50% by mass.
  • the content is preferably 0 to 30% by mass.
  • the content is preferably 0.00001 to 90% by mass, more preferably 0.00001 to 90% by mass. It is preferably 0.0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, more preferably 0.1 to 40% by mass, and still more preferably 1.0 to 30% by mass. It is preferable that the content is% by mass.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food or drink for suppressing vascular smooth muscle cell proliferation in the present invention, preferably 0.000001 to 90% by mass, More preferably, 0.0001 to 70% by mass, further preferably 0.001 to 60% by mass, further preferably 0.01 to 50% by mass, still more preferably 0.1 to 40% by mass, further preferably 1. It is preferable to contain 0 to 30% by mass.
  • ebaol and a physiologically acceptable salt thereof or a derivative thereof be contained as an active ingredient in the food or beverage for suppressing vascular smooth muscle cell proliferation in the present invention.
  • vellic acid and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient in the food and drink for inhibiting vascular smooth muscle cell proliferation in the present invention, preferably 0.000001 to 90% by mass, It is more preferably 0.0001 to 70% by mass, further preferably 0.001 to 60% by mass, further preferably 0.01 to 50% by mass, further preferably 0.1 to 40% by mass, and still more preferably 1.0 to 30% by mass. It is preferable that the content is contained by mass%.
  • the amount is preferably 0.001 to 90% by mass, and more preferably 0.001 to 90% by mass.
  • 0.0001 to 70% by mass more preferably 0.001 to 60% by mass, more preferably 0.01 to 50% by mass, more preferably 0.1 to 40% by mass, and still more preferably 1.0 to 100% by mass.
  • the content is preferably 30% by mass.
  • the food and drink for inhibiting vascular smooth muscle cell migration of the present invention can obtain more favorable effects by ingesting continuously.
  • the amount of the compound selected from the group consisting of the pentacyclic triterpenes, their physiologically acceptable salts, and their derivatives in the food and drink for inhibiting vascular smooth muscle cell migration of the present invention is generally specified. Not determined, based on the type of triterbene, the purpose of use, prevention or treatment, period of use, amount, age, sex, weight, etc. Just fine.
  • 0.0001 to 90% by mass more preferably 0.0001 to 80% by mass, still more preferably 0.001 to 70% by mass, further preferably 0.01 to 65% by mass, More preferably, 0.1 to 60% by mass, More preferably, 0.2 to 55% by mass, more preferably, 0.4 to 50% by mass, more preferably, 0.6 to 45% by mass, more preferably, 0.8 to 40% by mass, and furthermore, Preferably it is 1.0 to 35% by mass, more preferably 2.0 to 30% by mass. In any case, the higher the content, the stronger the effect. However, it is necessary to adjust the content in consideration of the purpose of use, period of use, amount, age, sex, weight, etc. of the target.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food or drink for inhibiting vascular smooth muscle cell migration in the present invention, preferably 0.000001 to 90% by mass, Preferably from 0.0001 to 80% by mass, more preferably from 0.001 to 70% by mass, more preferably from 0.01 to 65% by mass, more preferably from 0.1 to 60% by mass, more preferably from 0.2 to 60% by mass. 55% by mass, more preferably 0.4 to 50% by mass, still more preferably 0.6 to 45% by mass, further preferably 0.8 to 40% by mass, more preferably 1.0 to 35% by mass, and still more preferably Is preferably 2.0 to 30% by mass.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food or drink for suppressing vascular smooth muscle cell migration in the present invention, preferably 0.000001 to 90% by mass, More preferably, 0.0001 to 70% by mass, further preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, still more preferably 0.1 to 40% by mass, further preferably 1. It is preferable to contain 0 to 30% by mass.
  • the food and beverage for anti-cell proliferative vascular lesions of the present invention can obtain more favorable effects by continuous ingestion.
  • the compounding amount of the compound selected from the group consisting of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the food and drink for anti-cell proliferative vascular lesions of the present invention is generally Not stipulated, and may be determined appropriately according to the strength of the required effect based on the type of triterpene, the purpose of use for prevention or treatment, period of use, amount, age, sex, weight, etc. .
  • Less than Force s which is not limited to, preferably 0.0001 to 90% by mass, more preferably 0.0001 to 80% by mass, still more preferably 0.001 to 70% by mass, and still more preferably 0.01 to 65% by mass. More preferably, 0.1 to 60% by mass, more preferably, 0.2 to 55% by mass, more preferably, 0.4 to 50% by mass, more preferably, 0.6 to 45% by mass, more preferably, Is 0.8 to 40% by mass, more preferably 1.0 to 35% by mass, and even more preferably 2.0 to 30% by mass. In any case, the higher the content, the stronger the effect. However, it is necessary to adjust the content in consideration of the purpose of use, period of use, amount, age, sex, weight, etc.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food and drink for an anti-cell proliferative vascular lesion in the present invention, preferably 0.000001 to 90% by mass, Preferably, it is 0.0001 to 80% by mass, more preferably 0.001 to 70% by mass, further preferably 0.01 to 65% by mass, further preferably 0.1 to 60% by mass, and further preferably 0.2. To 55% by mass, more preferably 0.4 to 50% by mass, further preferably 0.6 to 45% by mass, further preferably 0.8 to 40% by mass, further preferably 1.0 to 35% by mass, Preferably, the content is 2.0 to 30% by mass.
  • the food or beverage for anti-cell proliferative vascular lesions of the present invention contains as an active ingredient an orifice or a physiologically acceptable salt thereof or a derivative thereof, it is preferably 0.00001. To 90% by mass, more preferably 0.0001 to 70% by mass, still more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, and still more preferably 0.1 to 40% by mass. More preferably, the content is 1.0 to 30% by mass.
  • ursolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food and drink for an anti-cell proliferative vascular lesion in the present invention, preferably 0.000001 to 90% by mass. , More preferably 0.0001 to 70% by mass, More preferably, it contains 0.001 to 60% by mass, more preferably 0.01 to 50% by mass, further preferably 0.1 to 40% by mass, and still more preferably 1.0 to 30% by mass.
  • baobaol and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food or beverage for anti-cell proliferative vascular lesions of the present invention, preferably 0.000001 to 90% by mass, more preferably Is from 0.0001 to 70% by mass, more preferably from 0.001 to 60% by mass, more preferably from 0.01 to 50% by mass, more preferably from 0.1 to 40% by mass, and even more preferably from 1.0 to 40% by mass. It is preferably contained in an amount of 30% by mass.
  • the food or beverage for an anti-cell proliferative vascular lesion contains vellic acid and a physiologically acceptable salt thereof or a derivative thereof as an active ingredient, preferably 0.0001 to 90% by mass, More preferably, 0.0001 to 70% by mass, further preferably, 0.1 to 60% by mass, more preferably 0.01 to 50% by mass, further preferably 0.1 to 40% by mass, and still more preferably 0.1 to 40% by mass.
  • the content is preferably 0 to 30% by mass.
  • vereline and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient in the food or beverage for anti-cell proliferative vascular lesions of the present invention, preferably 0.000001 to 90% by mass, more preferably Is from 0.0001 to 70% by mass, more preferably from 0.001 to 60% by mass, further preferably from 0.01 to 50% by mass, further preferably from 0.1 to 40% by mass, more preferably from 1 to 40% by mass.
  • the content is preferably 0 to 30% by mass.
  • the food and beverage for anti-intimal thickening of the present invention can obtain more favorable effects by continuous ingestion.
  • the compounding amount of the compound selected from the group consisting of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the food and drink for anti-intimal thickening of the present invention is not specified unconditionally.
  • Kind of kind, prevention or treatment Based on the purpose of use, period of use, amount of use, age, sex, weight, etc. of the target, it may be determined appropriately according to the strength of the required effect. Although not limited to the following, it is preferably ⁇ 0000:!
  • maslinic acid and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient in the anti-intimal thickening food or drink of the present invention, preferably 0.0001 to 90% by mass, more preferably 0.0001 to 80% by mass, more preferably 0.001 to 70% by mass, more preferably 0.01 to 65% by mass, more preferably 0.1 to 60% by mass, and still more preferably 0.2 to 60% by mass. 55% by mass, more preferably 0.4 to 50% by mass, still more preferably 0.6 to 45% by mass, more preferably 0.8 to 40% by mass, more preferably 1.0 to 35% by mass %, More preferably 2.0 to 30% by mass.
  • erythrodiol and a physiologically acceptable salt or a derivative thereof are contained as an active ingredient in the food and drink for anti-intimal thickening in the present invention, preferably 0.000001 to 90% by mass, more preferably 0.0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, further preferably 0.1 to 40% by mass, more preferably 1.
  • the content is preferably 0 to 30% by mass.
  • Persolic acid and its production as an active ingredient in the food and drink for anti-intimal thickening in the present invention When containing physically acceptable salt or derivative thereof, preferably 0.00 00:! ⁇ 90 mass 0/0, more preferably from 0.0001 to 70% by weight, rather more preferably 0.001 It is preferably contained in an amount of 0.1 to 50% by mass, more preferably 0.01 to 50% by mass, still more preferably 0.1 to 40% by mass, and still more preferably 1.0 to 30% by mass.
  • Baobal or a physiologically acceptable salt thereof or a derivative thereof is contained as an active ingredient in the anti-intimal thickening food or drink of the present invention, preferably 0.0001 to 90% by mass, more preferably 0%. 0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, still more preferably 0.1 to 40% by mass, more preferably 1.0 to 100% by mass. It is desirable to contain up to 30% by mass.
  • vertulinic acid and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient in the food and drink for anti-intimal thickening in the present invention, preferably 0.0001 to 90% by mass, more preferably Is from 0.0001 to 70% by mass, more preferably from 0.001 to 60% by mass, even more preferably from 0.01 to 50% by mass, further preferably from 0.1 to 40% by mass, more preferably from 1.0 to 100% by mass. It is preferably contained in an amount of up to 30% by mass.
  • vereline and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient in the food and drink for anti-intimal thickening in the present invention, preferably 0.0001 to 90% by mass, more preferably 0.0001 to 70% by mass, more preferably 0.001 to 60% by mass, more preferably 0.01 to 50% by mass, more preferably 0.1 to 40% by mass, and still more preferably 1.0 to 30% by mass. It is preferable that the content is contained by mass%.
  • the food and beverage for anti-atherosclerosis of the present invention can obtain more favorable effects by continuous ingestion.
  • the pentacyclic tongue in the anti-atherosclerotic food and drink of the present invention The compounding amount of the compound selected from the group consisting of triterpenes, their physiologically acceptable salts, and their derivatives is not necessarily specified, but the type of triterpenes, the purpose of use for prevention or treatment, and the use Based on the period, amount, age, sex, weight, etc. of the target, it may be determined appropriately according to the strength of the required effect.
  • 0.0001 to 90% by mass more preferably 0.0001 to 80% by mass, further preferably 0.001 to 70% by mass, and still more preferably 0.01 to 65% by mass. More preferably, 0.1 to 60% by mass, more preferably 0.2 to 55% by mass, more preferably 0.4 to 50% by mass, more preferably 0.6 to 45% by mass, more preferably 0.8 to 40% by mass, more preferably 1.0 to 35% by mass, and even more preferably 2.0 to 30% by mass.
  • the higher the content the stronger the effect.
  • maslinic acid and its physiologically acceptable salts or derivatives thereof are contained as active ingredients in the anti-atherosclerotic food and drink of the present invention, preferably 0.0001 to 90% by mass, more preferably 0. 0001 to 80% by mass, more preferably 0.001 to 70% by mass, more preferably 0.01 to 65% by mass, more preferably 0.1 to 60% by mass, and still more preferably 0.2 to 55% by mass.
  • % By mass, more preferably 0.4 to 50% by mass, still more preferably 0.6 to 45% by mass, still more preferably 0.8 to 40% by mass, and still more preferably 1.0 to 35% by mass. More preferably, the content is 2.0 to 30% by mass.
  • the anti-arteriosclerosis food or drink in the present invention contains erythrodiol and a physiologically acceptable salt thereof or a derivative thereof as an active ingredient, preferably 0.000001 to 90% by mass, more preferably 0.0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, further preferably 0.1 to 40% by mass, more preferably 1. 0-30% by mass Is preferred.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food or beverage for anti-atherosclerosis in the present invention, preferably 0.001 to 90% by mass, more preferably 0.001 to 90% by mass.
  • the content is preferably 30% by mass.
  • Baobal or a physiologically acceptable salt thereof or a derivative thereof is contained as an active ingredient in the food and drink for anti-arteriosclerosis according to the present invention, preferably 0.0001 to 90% by mass, more preferably 0.0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, still more preferably 0.1 to 40% by mass, more preferably 1.0 to 100% by mass.
  • the content is preferably 30% by mass.
  • beryric acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food or beverage for anti-atherosclerosis in the present invention, preferably 0.0001 to 90% by mass, more preferably 0.0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, still more preferably 0.1 to 40% by mass, and still more preferably 1.0 to 100% by mass.
  • the content is preferably 30% by mass.
  • the amount is preferably 0.0001 to 90% by mass, more preferably 0. 0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, still more preferably 0.1 to 40% by mass, more preferably 1.0 to 30% by mass. % Is preferred.
  • the food and drink for vascular disorders according to the present invention is characterized by containing a compound selected from the group consisting of pentagonal triterpenes, their physiologically acceptable salts and their derivatives, as described above.
  • the amount of the food and drink for vascular disorders according to the present invention differs depending on conditions such as the use, administration form, species, age, gender, weight, degree of symptoms, and degree of health of the administration subject.
  • the amount is, of course, an amount effective for preventing and / or treating arteriosclerosis generation and hyperplasia due to inhibition of proliferation and migration of vascular smooth muscle cells.
  • the food and drink for vascular disorders of the present invention can obtain more favorable effects by continuous ingestion.
  • the compounding amount of the compound selected from the group consisting of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the food and drink for vascular disorders according to the present invention is not generally defined, It may be determined as appropriate according to the strength of the required effect, taking into account the type of the species, the purpose of use such as prevention or treatment, the period of use, the amount, the age, gender, and weight of the subject.
  • 0.0001 to 90% by mass more preferably 0.0001 to 80% by mass, still more preferably 0.001 to 70% by mass, further preferably 0.01 to 65% by mass, More preferably, 0.1 to 60% by mass, more preferably, 0.2 to 55% by mass, further preferably, 0.4 to 50% by mass, more preferably, 0.6 to 45% by mass, more preferably 0.8% by mass. It is preferably from 40 to 40% by mass, more preferably from 1.0 to 35% by mass, and still more preferably from 2.0 to 30% by mass.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food and drink for a vascular disorder disease according to the present invention, preferably 0.001 to 90% by mass, more preferably 0.001 to 90% by mass.
  • the content is preferably 30% by mass.
  • erythrodiol and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food or drink for a vascular disorder disease according to the present invention, preferably 0.000001 to 90% by mass, more preferably 0% by mass. 0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, further preferably 0.1 to 40% by mass, more preferably 1.0 to 100% by mass. It is preferably contained in an amount of up to 30% by mass.
  • the food or drink for a vascular disorder according to the present invention contains persorbic acid and a physiologically acceptable salt thereof or a derivative thereof as an active ingredient, it is preferably 0.0001 to 90% by mass, more preferably Is from 0.0001 to 70% by mass, more preferably from 0.001 to 60% by mass, more preferably from 0.01 to 50% by mass, further preferably from 0.1 to 40% by mass, more preferably from 1.0 to 100% by mass. It is preferably contained in an amount of up to 30% by mass. .
  • ⁇ baol and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient in the food or drink for vascular disorders according to the present invention, preferably 0.0001 to 90% by mass, more preferably 0%. . 0001-70 mass%, rather still more preferably is 0.001 to 6.0 mass 0/0, more preferably from 0.01 to 50 wt%, more preferably from 0.1 to 40 wt%, more preferably 1.0 It is preferably contained in an amount of up to 30% by mass.
  • the content is preferably 0.001 to 90% by mass, more preferably 0.001 to 90% by mass. Is 0.0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, Preferably, the content is 0.1 to 40% by mass, more preferably 1.0 to 30% by mass.
  • bellin and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the food or drink for a vascular disorder disease in the present invention, preferably 0.0001 to 90% by mass, more preferably 0. 0001 to 70% by mass, more preferably 0.001 to 60% by mass, still more preferably 0.01 to 50% by mass, still more preferably 0.1 to 40% by mass, more preferably 1.0 to 30% by mass. It is preferable that the content is contained by mass%.
  • the dose required for suitably obtaining an anti-atherosclerotic effect is as follows: It depends on the form of ingestion, the gender, weight, physical condition, etc. of the subject, and is not particularly limited, but is, for example, at least 0,000 lg / day, preferably at least 0,0 lg / day, particularly preferably at least 0, lg / day. It is.
  • the food and beverage for anti-arteriosclerosis in which the vascular disorder disease is arteriosclerosis according to the present invention can obtain more favorable effects by continuous ingestion.
  • the compounding amount of the compound selected from the group consisting of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the food and drink for anti-atherosclerosis of the present invention is not generally defined, It may be appropriately determined according to the strength of the required effect, taking into account the type of the species, the purpose of use such as prevention or treatment, the period of use, the amount, the age, gender, and weight of the subject.
  • 0.0001 to 90% by mass more preferably 0.0001 to 80% by mass, still more preferably 0.001 to 70% by mass, and still more preferably 0.01 to 65% by mass.
  • % By mass more preferably 0.6 to 45% by mass, still more preferably 0.8 to 40% by mass, further preferably 1.0 to 35% by mass, more preferably 2.0 to 30% by mass. .
  • the higher the content the stronger the effect.
  • the anti-restenotic food and drink according to the present invention in which the vascular disorder is restenosis after PTCA, can obtain more favorable effects by continuous ingestion.
  • the compounding amount of the compound selected from the group consisting of the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives in the anti-restenotic food and drink of the present invention is not unconditionally specified. It may be appropriately determined according to the strength of the required effect, taking into account the type of the species, the purpose of use such as prevention or treatment, the period of use, the amount, the age, sex, and weight of the subject.
  • 0.0001 to 90% by mass more preferably 0.0001 to 80% by mass, further preferably 0.001 to 70% by mass, and still more preferably 0.01 to 65% by mass. More preferably, 0.1 to 60% by mass, further preferably, 0.2 to 55% by mass, more preferably, 0.4 to 50% by mass, more preferably, 0.6 to 45% by mass, more preferably, 0.1 to 50% by mass. It may be 8 to 40% by mass, more preferably 1.0 to 35% by mass, and even more preferably 2.0 to 30% by mass. In any case, the higher the content, the stronger the effect. However, it is necessary to adjust the content in consideration of the purpose of use, period of use, amount, age, sex, weight, etc. of the target.
  • maslinic acid and a physiologically acceptable salt thereof, or derivatives thereof have an inhibitory effect on vascular smooth muscle cell proliferation, an inhibitory effect on vascular smooth muscle cell migration, an inhibitory effect on intimal hyperplasia, an anti-arterial sclerosis and the like. It is preferred because it has very strong effects such as anti-cell proliferative vascular lesion effect, anti-atherosclerosis, and anti-vascular disorder disease effect such as anti-restenosis after PTCA. That is, maslinic acid and its physiologically acceptable salts, or their induction!
  • the present invention relates to a food and drink for vascular lesions, and a food and drink for vascular disorders such as anti-atherosclerosis and anti-restenosis after PTCA.
  • maslinic acid can be obtained from plants that are relatively constantly cultivated as olive plants and have already been crushed as edible oil. Excellent and preferred. In addition, it can be reduced in cost because it can be supplied constantly, which is very preferable.
  • the food and drink containing maslinic acid according to the present invention which has the desired effects, can obtain more favorable effects by continuous ingestion.
  • maslinic acid and its physiologically acceptable salts or derivatives thereof are preferable as health foods and the like because some of them are obtained from natural products that have already been tested.
  • the amount of maslinic acid and its physiologically acceptable salt or its derivative at that time is not stipulated in general, and the purpose of use, whether to prevent or treat, the period of use, amount, age of use , Gender, weight, etc., may be determined as appropriate according to the strength of the required effect.
  • 0.0001 to 90% by mass more preferably 0.0001 to 80% by mass, further preferably 0.01 to 70% by mass, and still more preferably 0.01 to 65% by mass. More preferably, 0.1 to 60% by mass, more preferably, 0.2 to 55% by mass, more preferably, 0.4 to 50% by mass, more preferably, 0.6 to 45% by mass, and still more preferably, 0.2 to 45% by mass. It may be 8 to 40% by mass, more preferably 1.0 to 35% by mass, and even more preferably 2.0 to 30% by mass. In any case, the higher the content, the stronger the effect. However, it is necessary to adjust the content in consideration of the purpose of use, the period of use, the amount, the age, sex, weight, etc. of the target.
  • the food and drink of the present invention have improved functions, in particular, an inhibitory effect on vascular smooth muscle cell proliferation, an inhibitory effect on vascular smooth muscle cell migration, an inhibition of intimal hyperplasia, and an anti-cell proliferative blood vessel such as anti-atherosclerosis.
  • ingredients that can be expected to have synergistic effects antioxidant ingredients, oily ingredients to improve absorption in the body and increase the efficiency of the effect, various vitamins and minerals for nutritional enhancement And amino acids.
  • Components that can be expected to have synergistic effects include brassicasterol, campesterol, stegmasterol, 7-ergosterol, sitosterol, isofucosterol, 7-stigmasterol, cycloartol, 24methylenecycloartanol, cyclo Plant sterols such as brassinol, phenylpropanoides such as gingerol, curcumin, bergamotin and ACA, flavone, catechin, quercetin, flavonoids such as leucoanthocyanidin, luteolin, cardamonin, and nobiletin; And carotenoids such as astaxanthin and derivatives thereof, dietary fibers such as pectin, alexin, ferulic acid and derivatives thereof, and the like. These 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, tocopherol and tocotrienol and their derivatives, and dibutylhydroxyl.
  • Sugars such as toluene, butylhydroxyanisole, disodium ethylenediaminetetraacetate, calcium sodium ethylenediaminetetraacetate, and ellagic acid gallate, and derivatives thereof, sodium sulfite and sodium hyposulfite.
  • Sulfuric acid compounds such as sulfur disulfide, ferulic acid derivatives such as aoryzanol, rutin and its derivatives, sesa Lignans and their glycosides, such as min, ebisesamine, sesaminol, sesamolin, and sesamol, carotenoids such as carotene and derivatives thereof, flavonone, catechin, quercetin, isoquercetin, leukoanthocyanidin, genistin, Genistin, 6 "-0-acetylgenistin, 6" -0-malonilgenistin, soybean, daidzein, 6 "-0-acetyldizin, 6" - ⁇ -1 malonyldizin, glycitin, Glycitin, 6 "-0-acetylglycitin, 6" -0-malonylglinitine, pellarin, quercetin, kaempfero, flavonoids such as miloeste quinones
  • Nicotinic acids such as pyridoxine, nicotinic acid amide, and benzyl nicotinate; pyrirubin, mannitol, Liptophan, histidine, nordihydroguaiaretic acid and the like can be mentioned.
  • These antioxidants are preferable because they can be expected to have an overall synergistic effect on the human body, etc., due to the antioxidant effect of preventing lifestyle-related diseases and the anti-aging effect.
  • the oily component is not particularly limited, in addition to vegetable oils such as soybean oil, rapeseed oil, sesame oil, and olive oil, animal oils such as lard, beef tallow, fish oil, etc., but is not particularly limited.
  • vegetable oils such as soybean oil, rapeseed oil, sesame oil, and olive oil, animal oils such as lard, beef tallow, fish oil, etc.
  • the obtained MCT, MLCT diglyceride, monoglyceride II, structural fats and oils designed for the structure of fatty acids, and the like can be mentioned. 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.
  • the food of the present invention may be mixed with raw materials used for ordinary food and drink.
  • 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, Vegetable 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, glucose, sorbitol, honey and other sweeteners, Umami seasonings such as MSG (monosodium glutamine),
  • the above components can be appropriately designed and blended depending on the purpose of use.
  • the effect can be synergistically or complemented depending on the type of the absorption and the effect of the effect, or a preferable mode of use can be obtained.
  • isoflavones and derivatives thereof are excellent in water solubility, and by acting on a living body simultaneously with a specific pentagonal triterpene which is generally an oil-soluble substance of the present invention, it has an antiestrogen inhibitory effect. Synergistic effects are achieved through various water and lipid-mediated metabolic pathways, and the effects can be expected to be synergistic.
  • foods and drinks for vascular disorders which simultaneously contain the specific pentacyclic triterpenes and isoflavonide, etc., which are the objects of the present invention, have physiological properties such as antioxidative and antiestrogenic effects of isode.
  • Active and synergistic Can be expected to be activated.
  • the present invention is not limited thereto.
  • the foods and drinks of the present invention include various foods and drinks such as confectionery, processed foods, compounded fats and oils, processed fats and oils, dairy products and beverages.
  • the shape and properties are not particularly limited, and may be any of solid, semi-solid, gel, liquid, powder, and the like.
  • Japanese confectionery such as oysters, rice crackers, rice crackers, buns, candy, cookies, biscuits, crackers, cereal foods, pies, castella, donuts, pudding, sponge cake, ⁇ ⁇ ful, butter cream, and casserole cream
  • chocolate, chocolate confectionery, caramel, candy, queuing gum, jelly, hot cake, bread, confectionery bread, etc., snacks such as potato chips, ice cream, ice candy, ice cream, etc.
  • Lactic acid drinks Lactic acid drinks, lactic acid bacteria drinks, concentrated milk drinks, fruit drinks, pulp drinks, functional drinks, soft drinks such as carbonated drinks, luxury goods such as green tea, tea, coffee, cocoa, etc., and these drinks, sake and wine Liquor, brandy, whiskey, medicinal liquor Dairy products such as dairy products, milk, fermented milk, processed milk, cheese, etc., processed soybean foods such as soy milk, tofu, jam, fruit pickled in syrup, flower paste, pear paste, full paste, etc.
  • Cereals, pickles, udon noodles, pasta and other cereal products, ham, sausage, bacon, dried sausage, beef jerky, hamburger and other meat products, fish meat ham, fish meat sausage, kamaboko, chikuwa, Fish and shellfish products such as rice bean, dried fish and shellfish, various sections such as bonito, mackerel, aji, salted fish such as sea urchin, squid, dried squid, fish and other dried fish, and smoked products such as salmon Ri, small fish, shellfish, wild vegetables, shiitake mushrooms, kelp, etc., retort foods such as kareichi, shichiyu, miso, soy sauce, sauce, ketchup, bouillon, grilled meat evening meal, curry rice, stew base, Soup Various seasonings, such as rice and dashi, rice, Examples include fats and oils such as formulated fats and oils, margarine, shortening, mayonnaise, and dressings, and various ranges and frozen foods
  • the pentacyclic triterpenes in the food and drink of the present invention are originally fat-soluble substances in general, compounded fats and oils and processed foods and the like are preferred as the food and drink of the present invention from the aspect of solubility.
  • a compounded oil and fat examples thereof include a compounded oil and fat containing natural or artificially obtained pentacyclic triterpenes dissolved in ordinary oil and fat. Squeezing of pentacyclic triterpenes in seeds by adjusting extraction conditions and squeezing pentacyclic triterpenes in seeds, and pentacyclic triterpenes present in oil by adjusting refining conditions And oils and the like in which the residue is left.
  • the pentacyclic 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 a trace component contained in the other fats and oils can be expected.
  • oils and fats are preferable from the viewpoint of production.
  • processed oils such as magarine, shortening, mayonnaise, and dressing It can be said that a processed oil and fat product such as the above is preferable.
  • 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.
  • pentacyclic triterpenes their physiologically acceptable salts and their derivatives in foods and drinks
  • pentacyclic triterpenes Or a derivative having an alcohol ester group, a derivative having a fatty acid ester group, a derivative having an alkoxy group, an alkoxymethyl group
  • these are relatively fat-soluble, they can be suitably applied to oil-based foods and drinks.
  • physiologically acceptable salts or glycosides of pentacyclic triterpenes can also be blended, but in this case, it is preferable to use a milky lantern.
  • physiologically acceptable salts or glycosides of pentacyclic triterpenes are preferred. Since these are relatively water-soluble, they can be suitably applied to K-based foods and drinks. Of course, it is also possible to combine pentacyclic triterpenes or derivatives thereof, but in this case, it is preferable to use an emulsifier.
  • Eating and drinking the food and drink of the present invention provides an inhibitory effect on vascular smooth muscle cell proliferation, an inhibitory effect on vascular smooth muscle cell migration, an inhibitory effect on intimal hyperplasia, an anti-cell proliferative vascular lesion effect such as anti-atherosclerosis, and an anti-arterial sclerosis. It is effective by absorbing pentacyclic triterpenes, their physiologically acceptable salts and their derivatives into the body, which have anti-vascular disorders such as anti-restenosis after PTC and PTC. 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 above pentacyclic triterpenes, their physiologically acceptable salts and their derivatives can be synthesized or extracted from natural products. In nature, it can be obtained by extracting it from the above-mentioned plant, and more specifically, by extracting it with water and / or an organic solvent, and further concentrating and / or fractionating and purifying it. it can.
  • each plant can be extracted with water and / or an organic solvent, and the extract can be further subjected to a solvent extraction method, a method using a difference in solubility with impurities, a fractionation precipitation method, a recrystallization method, an ion exchange resin method, Separation and purification can be carried out by using a liquid chromatography method or the like alone, in an appropriate combination, or repeatedly.
  • a solvent extraction method a method using a difference in solubility with impurities
  • a fractionation precipitation method e.g., a recrystallization method
  • an ion exchange resin method Separation and purification can be carried out by using a liquid chromatography method or the like alone, in an appropriate combination, or repeatedly.
  • the effects of contaminants derived from natural products are eliminated, and colorless to pale colors and / or odorless to almost odorless are preferable. No.
  • 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.
  • the olive oil when taken in its original form, only a small amount of the pentacyclic triterpenes targeted by the present invention can be ingested, but the 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.
  • pentagonal triterpenes contained in olive oil and the like are generally fat-soluble substances, so they are usually present in fats and oils in general. Therefore, it is difficult to mix them in water-based foods and drinks. If the pentacyclic triterpene is isolated from the product, it can be added to 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.
  • 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.
  • the present invention is preferable because the effects of the present invention, that is, the effect of inhibiting vascular smooth muscle cell proliferation and the effect of inhibiting vascular smooth muscle cell migration can be obtained.
  • an example of the extraction of maslinic acid will be described.
  • maslinic acid and a physiologically acceptable salt thereof, or a derivative thereof can be naturally obtained by extracting from the above-mentioned plant.
  • Physiologically acceptable salts include olive plant Can be extracted with water and / or an organic solvent, and the extract can be further extracted by solvent extraction, a method using the solubility difference with impurities, fractional precipitation, recrystallization, ion-exchange resin, liquid chromatography These can be separated and purified by single use or in an appropriate combination, or by repeated use.
  • Olive plants (Ole ae europ ae a L.) can be used regardless of the locality of production in Japan or Europe, edible or oiled.
  • the maslinic acid and / or a physiologically acceptable salt thereof contained in the food and drink for vascular diseases of the present invention can be obtained mainly from fruits or seeds of a natural olive plant. It can be obtained from seed coats, leaves, stems and buds. In addition, it can be suitably obtained from these dried, pulverized, and degreased products. Of these, defatted fruits (including pericarp) and dried and ground pericarp are preferred.
  • products generated in the process of producing olive oil such as pressed residue, extracted residue, squeezed residue, pressed oil, extracted oil, degummed oil residue, deoxidized oil residue, dark oil residue, waste oil, waste It can be obtained from decolorizing agents, deodorizing scum, oiled juices, wastewater and waste filter media. Of these, the oil residue is preferred.
  • the fruits of the above-mentioned olive plants and their defatted products are added with water, etc., or when humidification treatment such as steaming is performed, the fruits of these olive plants and their defatted products are appropriately treated. Because it swells, the extraction efficiency is improved, which is preferable.
  • the defatted product of the olive plant contains maslinic acid and / or its physiologically acceptable salt at a high concentration, and the obtained maslinic acid and / or its physiologically acceptable salt This is preferred because it is not necessary to remove oil from the salt.
  • 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.
  • the lipid component contained in the plant plant or the defatted product may be a hydrocarbon such as pentane, hexane, heptane, a lower fatty acid alkyl ester such as ethyl acetate, or a known water-insoluble organic solvent such as getyl ether. Extract and remove with one or more species A degreased product obtained by removing and repeating this washing treatment as needed can also be suitably used. By extracting the olive plant with water and / or an organic solvent, maslinic acid and / or a physiologically acceptable salt thereof contained in the food / drink for vascular disease of the present invention can be obtained.
  • the organic solvent used for obtaining maslinic acid and / or a physiologically acceptable salt thereof from the olive plant may be any of a hydrophilic organic solvent and a hydrophobic organic solvent.
  • a hydrophilic organic solvent methyl alcohol, ethyl alcohol, glycerin, propylene glycol, alcohols such as 1,3-butylene glycol, acetone, tetrahydrofuran, acetonitrile, 1,4-dioxane, pyridine, dimethyl
  • Known organic solvents such as sulfoxide, N, N-dimethylformamide, and acetic acid are exemplified.
  • hydrophobic organic solvent hexane, cyclohexane, carbon tetrachloride, chloroform, dichloromethane, 1,2-
  • organic solvents such as dichloroethane, ethyl ether, ethyl acetate, benzene, and toluene are exemplified. These organic solvents can be used alone or in combination of two or more.
  • 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 aqueous solvents thereof.
  • the extraction conditions are not particularly limited.
  • the temperature is 5 ° C to 95 ° C (: preferably 10 ° C to 90 ° C, more preferably 15 ° C to 85 ° C, and room temperature. But extract well be able to. 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.
  • the extraction can be carried out by shaking extraction or an extractor equipped with a stirrer.
  • the extraction time is from several minutes to several hours, depending on other extraction conditions. The longer the time, the more the extraction is performed. However, the extraction time may be appropriately determined depending on production conditions such as production equipment and yield.
  • 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.
  • water containing a lower alcohol content of at least 10% by mass is considered. It is preferred to extract with a lower alcohol. Further, it is preferable to use a hydroalcohol having a lower alcohol content of 10% by mass to 95% by mass, and most preferably a hydrous lower alcohol having a lower alcohol content adjusted to 30% by mass to 95% by mass. Is 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, or a 2-alcohol.
  • Well-known solvents such as tertiary alcohols such as methyl-2-propanol and liquid polyhydric alcohols such as ethylene glycol, propylene glycol and 1,3-butylene glycol can be used. 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 above-mentioned primary, secondary, tertiary, or liquid polyhydric alcohols, and a combination of one or more of these. Can be used.
  • 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.
  • 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 oil-soluble components such as triglyceride sterol and tocopherol, and it is not necessary to remove and purify these components.
  • defatted matter includes residue after oiling, it is possible to use pressed cake and extracted cake obtained by squeezing orifice oil. Since waste or feed is used, it is an excellent method in terms of production cost.
  • maslinic acid to be contained in the food and drink for vascular diseases of the present invention Preferably, and / or a physiologically acceptable salt thereof is concentrated.
  • the concentration conditions are not particularly limited, and examples thereof include a method using solubility in water.
  • the maslinic acid and / or its physiologically acceptable salt contained in the food and drink for vascular disorders of the present invention is a compound having relatively low polarity and poor water solubility.
  • the crude extract from olive plants is difficult to dissolve in water and Z or insoluble in water. By dividing into, it can be concentrated significantly.
  • Crude extraction from olive plants Ingredients such as poorly water-soluble are significantly superior in anti-atherosclerotic effect compared to whole crude extracts from olive plants, and maslinic acid and / or its physiologically acceptable It can be confirmed that the resulting salt is concentrated.
  • Insoluble components and the like 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.
  • maslinic acid and / or its physiologically acceptable salt contained in the food and drink for vascular disorders according to the present invention may be concentrated by liquid-liquid distribution using a combination of common solvents, if necessary.
  • a combination of common solvents for example, a combination of water and a hydrophobic organic solvent can be mentioned.
  • the hydrophobic organic solvent include hexane, carbon tetrachloride, chloroform, dichloromethane, 1,2- Known organic solvents such as dichloroethane, getyl ether, ethyl acetate, n-butanol, benzene and toluene are exemplified. Of these, hexane, ethyl acetate and n-butanol are preferred.
  • maslinic acid and / or its physiologically acceptable salts 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 its physiologically acceptable salt can be easily concentrated.
  • maslinic acid and / or a physiologically acceptable salt thereof contained in the food and drink for a vascular disorder disease of the present invention is preferably subjected to fractionation and purification from the above-mentioned extract and / or concentrate. .
  • the concentration can be more than the above concentration, and the target component can be isolated.
  • the advantages of the fractionation / purification treatment include the fact that the anti-atherosclerosis effect and the like can be significantly improved, and that the impurities can be removed. That is, when the fractionation and purification treatment is performed, maslinic acid and / or a physiologically acceptable salt thereof can be obtained as white crystals. Advantages such as being able to be suitably blended without adding extra color are preferable.
  • the method of fractionation / purification is difficult to specify in general, but examples include recrystallization method, fractional precipitation method, and method using chromatography.
  • the method utilizing liquid chromatography among the chromatographic methods is capable of improving the yield without decomposing maslinic acid and / or a physiologically acceptable salt thereof contained in the food and drink for vascular disorders of the present invention. It is preferable because it can be fractionated well.
  • Specific examples of liquid chromatography include normal-phase liquid chromatography, reversed-phase liquid chromatography, thin-layer chromatography, paper chromatography, and high-performance liquid chromatography (HPLC).
  • Either method can be used for fractionating and purifying maslinic acid and / or a physiologically acceptable salt thereof contained in the food and drink for vascular disorders of the present invention.
  • normal phase liquid chromatography reversed-phase liquid chromatography, and high-performance liquid chromatography (HPLC) are preferable in consideration of the resolution, the throughput, the number of steps, and the like.
  • HPLC high-performance liquid chromatography
  • 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-ethyl acetate, a mixture of chloroform and methyl alcohol as the mobile phase, and a crude extract from an olive plant or its crude extract was prepared.
  • the concentrate is supplied at a load ratio of 0.1 to 5% (wt (mass) / v (volume)), and the concentration is determined by a continuous elution method using a single mobile phase or a stepwise elution method in which the solvent polarity is gradually increased. Is eluted.
  • the reversed phase liquid chromatography refers to the following method, for example. That is, for example, a column was prepared in which silica (ODS) to which octane decylsilane was bonded was used as a stationary phase, a water-medium mixture, a water-acetonitrile mixture, a water-acetone mixture, or the like as a mobile phase. Crude plant extract or its concentrate at a load factor of 0.1 to 5% (wt (mass) / v (volume)) This is a method in which a predetermined fraction is eluted by a stepwise elution method in which the polarity is sequentially reduced.
  • 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.
  • maslinic acid and / or a physiologically acceptable salt thereof can be very concentrated and can be obtained in a state where power and impurities have been removed.
  • the purity of maslinic acid and / or its physiologically acceptable salt can be adjusted, and the strength of the anti-atherosclerotic effect as required , Characteristics, etc. can also be designed.
  • the concentration treatment can be preferably repeated, and different concentration treatments can be combined.
  • the fractionation / purification treatment can be preferably repeated, and different fractionation / purification treatments can be combined.
  • fractionation and purification may be performed after concentration
  • fractionation and purification may be performed after fractionation and purification
  • fractionation and purification may be performed after concentration. It can also be processed.
  • combinations other than the above-mentioned combinations may be used.
  • the hydrophilic organic solvent is removed from the obtained extract, and water is added if necessary, followed by stirring.
  • the water-insoluble content precipitated in the solution is concentrated.
  • the precipitated water-insoluble matter can be recovered by filtration, centrifugation, etc.
  • the aqueous solution can be subjected to treatment such as addition of water and stirring, if necessary.
  • the extract in the dried state obtained by removing water and / or the hydrophilic organic solvent from the extract obtained from the olive plant is also subjected to treatment such as addition of water and stirring in the same manner as described above, and is subjected to filtration and the like.
  • the concentration treatment can be performed by recovering the water-insoluble matter. According to this concentration method, since the treatment is performed in an aqueous system, safety is superior to concentration using a solvent, and the range of usable equipment is wide. Also, since it contains almost no oil, it is also excellent in the efficiency of concentration and purification, which is preferable. These concentrates are fractionated and purified by normal-phase and / or reverse-phase chromatography and / or recrystallization to obtain highly purified maslinic acid and / or its physiologically acceptable A salt 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-hydrophobicity is obtained.
  • Concentration treatment can be performed by liquid-liquid distribution with a neutral organic solvent.
  • the extract in the dry state can be concentrated by adding water and then adding a hydrophobic organic solvent in the same manner as described above, so that the extract can be concentrated in a liquid-liquid distribution with a water-hydrophobic organic solvent. it can.
  • 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.
  • 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.
  • it is used in a ratio of 8: 2 to 2: 8.
  • the total content of maslinic acid and physiologically acceptable salts thereof in a mixture of maslinic acid and a physiologically acceptable salt thereof is preferably 95% or more, more preferably 9% or more. 5% to 99.9%.
  • the content can be measured, for example, by gas chromatography.
  • the food and drink for a vascular disorder disease of the present invention can contain maslinic acid and / or a physiologically acceptable salt thereof. Food and drink for diseases can also be obtained. In addition, by adjusting the degree of concentration, purification, etc., the concentration of maslinic acid and / or its physiologically acceptable salt can be adjusted, and it can be suitably blended in foods and drinks for vascular disorders. Can be.
  • anti-atherosclerotic substances can be used in combination, which makes it possible to design a detailed anti-atherosclerotic effect, and greatly increases the synergistic effect with other anti-atherosclerotic substances.
  • a strong anti-atherosclerotic effect can also be expected.
  • olive oil contains maslinic acid
  • the use of olive oil as an oily component in the food and drink for vascular disorders of the present invention provides a more favorable anti-atherosclerotic effect and the like. Therefore, it is preferable.
  • maslinic acid and / or a physiologically acceptable salt thereof When maslinic acid and / or a physiologically acceptable salt thereof is extracted from an olive plant, oleanolic acid and / or a physiologically acceptable salt thereof are simultaneously extracted. And / or a physiologically acceptable salt thereof is excellent in compatibility with maslinic acid, so that these mixtures can be directly blended with the food and drink for vascular disorders of the present invention.
  • This is preferable because a synergistic effect can be expected with respect to the physiological effect of each, and particularly, a synergistic effect can be expected with respect to the anti-atherosclerotic effect of maslinic acid and / or its physiologically acceptable salt in the present invention.
  • maslinic acid and / or its physiologically acceptable salts When extracting, separating and purifying maslinic acid and / or its physiologically acceptable salts from olive plants, by adjusting the conditions, It can also be obtained as a mixture with oleanolic acid and / or a physiologically acceptable salt thereof. It can also be obtained by isolating a physiologically acceptable salt and mixing it later. 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 present invention relates to a compound selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, verinic acid, veline and physiologically acceptable salts thereof, and derivatives thereof as an active ingredient.
  • maslinic acid erythrodiol
  • ursolic acid ursolic acid
  • ebaol verinic acid
  • veline veline
  • physiologically acceptable salts thereof and derivatives thereof as an active ingredient.
  • maslinic acid, erythrodiol, ursolic acid, evacitol, veric acid, veline and their physiologically acceptable salts, or derivatives thereof have an inhibitory effect on vascular smooth muscle cell proliferation and / or Excellent in vascular smooth muscle cell migration inhibitory effect, anti-cell proliferative vascular lesion effect such as intimal hyperplasia suppression and anti-atherosclerosis, and anti-vascular disease effects such as anti-atherosclerosis and anti-restenosis after PTCA.
  • the maslinic acid, erythrodiol, ursolic acid, ebaol, verpulinic acid, veline and their physiologically acceptable salts, or derivatives thereof, of the present invention are obtained from natural plants. Any of those artificially obtained can be suitably used, and particularly when used as a raw material for various preparations, the higher the purity, the better.
  • defatted olive lees are extracted with an ethanol solution, concentrated by drying, and then purified by chromatography. Edible oils and fats contained in the same amount.
  • a dressing containing 1% by mass or more of maslinic acid which is obtained by extracting oily cake of olive with an ethanol solution, concentrating by drying, and then purifying by chromatography. .
  • olive oil cake is extracted with an ethanol solution.
  • the defatted cake of the olive is extracted with an ethanol solution, concentrated by drying, and then purified by chromatography.
  • the maslinic acid is purified in an amount of 0.5% by mass or more. Containing margarine.
  • mayonnaise containing 1% by mass or more of maslinic acid, which is obtained by extracting oily cake of olive with an ethanol solution, concentrating by drying, and then purifying by chromatography. .
  • Example 1 The pentacyclic triterpenes used in column 1 were erythrodiol (Funakoshi), persolic acid (Wako Pure Chemical), Baol (Funakoshi), berylic acid (Funakoshi), and Bellin. (Manufactured by Funakoshi) was purchased as a reagent. Those of HPLC grade were used as they were, and those which were not were dissolved in ethanol heated to the boiling point until saturated, cooled, recrystallized, filtered and dried. The maslinic acid used was extracted and purified from a force-orifice plant described below with reference to an example, and was confirmed to have a purity of 95%.
  • this concentrate was fractionated by silica gel column chromatography using a column packed with about 40 times (400 g) silica gel.
  • the crude maslinic acid fraction was further purified by ODS column chromatography using a column packed with about 30 times (60 g) of octyl decylsilicone gel.
  • vacuum drying was performed to obtain 1.51 g of purified maslinic acid 1.
  • this concentrate was fractionated by silica gel column chromatography using a column packed with about 40 times (500 g) silica gel.
  • the crude maslinic acid fraction was purified by ODS column chromatography using a column packed with about 30 times (80 g) of octyl decylsilicone gel.
  • vacuum drying was performed to obtain 2.06 g of purified maslinic acid 2.
  • the extraction residue of Italian olive obtained in the oil production process was added to 10 kg of ethanol and 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.
  • this extract was subjected to silica gel column chromatography using a column packed with about 40 times (1400 g) silica gel.
  • eluting miscellaneous unnecessary components with an eluent of hexane: ethyl acetate 3: 1 of about 10 times (14 L) of the packed silica gel, and then 2.5 times (350 OmL)
  • the hexane: ethyl acetate 1: 1 eluent elutes miscellaneous unnecessary components.
  • maslinic acid 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, persolic acid, baol, veric acid, and verin were obtained as follows.
  • maslinic acid 1.0 g was dissolved in 20 OmL of anhydrous dimethylformamide, 144.Omg of imidazole and 35 ODL of triethylsilyl chloride were added at 0 ports, and the mixture was tightly stoppered 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 hydrogen carbonate solution, and three times with pure water, and then magnesium sulfate. And left overnight.
  • the pentacyclic triterpenes were added to a DMEM medium containing the pentacyclic triterpenes to the concentrations shown in Table 1 and cultured for 48 hours.
  • A1 amar B1ue TM manufactured by Alamar
  • the cells were further cultured for 4 hours.
  • the fluorescent substance generated by the oxidation-reduction reaction of the cells was measured with a fluorescence spectrophotometer, and the cell growth inhibition rate was calculated by comparing with the fluorescence intensity of the control group.
  • cell morphology was also observed to determine the cytotoxicity of the pentacyclic triterpenes.
  • Table 1 shows the results as the growth inhibition rate.
  • Rat vascular smooth muscle cell line A 7 r 5 (purchased from ATCC), at a density of 3xl 0 5 cells / 75 cm 2 tissue culture flask (Nunc Co., Ltd.), DMEM medium (Nacalai containing 10% fetal bovine serum (Manufactured by Tesque). After entering Ru 11 days late logarithmic growth phase, 0.
  • the number of cells that migrated to the lower surface of the chemotaxel membrane was measured after staining the cells with Dif f-Quik staining (manufactured by Kokusai Reagents) and compared with the number of cells in the control group to suppress cell migration. The rate was calculated.
  • the control group was the group to which only the solvent in which the pentacyclic triterpene was dissolved was used as the control group, and the number of migrated cells obtained in the control group was taken as 100%.
  • the migration inhibition rate was calculated. That is, Equation 2 is satisfied.
  • Migration inhibition rate (%) 100-(number of cells in test substance-added group / number of cells in control group) X 100
  • Wistar female rats (15-week-old) were treated with AIN-93 composition powder for 1 week After preliminary breeding, the animals were divided into 8 groups (4 animals per group). Under anesthesia with pentobarbi, the dorsal position was fixed, the left external carotid artery was exposed, and a catheter was inserted from the external carotid artery to the common carotid bifurcation. The endothelial cells were detached by inflating the balloon at that point and pulling it to the external carotid artery while applying rotation. After repeating this operation four times, the surgical site was sutured. Each test substance shown in Table 4 was suspended in cottonseed oil and orally administered at a dose of 20 Omg / kg once a day using a probe.
  • the control group was a group to which only cottonseed oil in which pentagonal triterpenes were suspended was used as a control group, and the area ratio of the media to the intima obtained in the control group was 100%. From the area ratio of the media to the media in the pentacyclic triterpene-administered group, the intimal hyperplasia inhibition rate was calculated. That is, Equation 3 is as follows.
  • Intimal hyperplasia inhibition rate (%) 100-(area ratio of test substance administration group / area ratio of control group) X 100
  • NZW ⁇ egrets male, 2-2.5 kg were pre-fed for 1 week on a powdered diet (cholesterol diet) with 1% cholesterol containing AIN-93, and divided into 8 groups (5 birds per group).
  • the animals were bred on a cholesterol diet containing 1% of each test substance shown in Table 3 and once a day on a restricted diet (40 g / kg) for 8 weeks. Eight weeks later, the animals were sacrificed under pentobarbital anesthesia, dissected, and the aorta was removed.
  • Arteriosclerosis inhibition rate (%) 100-(Ratio of atherosclerotic lesion area to total aortic lumen area of test substance administration group / Ratio of atherosclerotic lesion area to total aortic lumen area of control group) l0 0
  • the anti-atherosclerosis inhibitory effect was evaluated by the above method. The results are shown in Table 4 as the arteriosclerosis inhibition rate
  • maslinic acid, erythrodiol, persolic acid, evanol, vericulinic acid, veline, and their physiologically acceptable salts, or derivatives thereof can have an excellent arteriosclerosis inhibitory effect. Revealed, anti-atherosclerotic food and drink It was found to be useful as an object.
  • the acute toxicity test was performed by the following method. Wistar female rats (6 weeks old, average body weight: 160 g) were pre-fed for 1 week on a powdered diet containing AIN_93 composition, and then 6 groups (8 animals per group) ) And maslinic acid-administered group, erythrodiol-administered group, persolic acid-administered group, ebaol-administered group, beryric-acid-administered group, and beverin-administered group. Each test substance was suspended in cottonseed oil and administered orally by force using a sonde so that the concentration became 2000 mg / kg body weight. Subsequently, the animals were bred on a powdered feed having a composition of AIN-93, the prognosis was observed two weeks after administration, and two weeks later, the autopsy was performed on the internal state of the flesh by dissection.
  • each pentacyclic triterpene is more than 2000 mg / kg of body weight, which is extremely excellent in safety, and ingested as a form of food and drink for vascular disorders. It turns out that it is also possible to do.
  • MLCT 32.0 g At the above mixing ratio, first put the raw materials excluding MLCT into a warmable vessel equipped with a stirrer, and stir at 100 rpm with a propeller stirrer to adjust the product temperature to 90 ° C. And stirred for 25 minutes while maintaining the product temperature at 90 ° C. Then, the product was cooled until the product temperature reached 20 ° C, and dressing was obtained together with the MLCT.
  • Purified maslinic acid of Production Example 1 15.0 g Vegetable sterol 1.0 g Safflower oil 989.0 g While maintaining the above conditions, the mixture was thoroughly mixed and dissolved using a stirrer until the whole was clarified to produce an edible oil mixture.
  • Rapeseed oil 42.0 g Hardened rapeseed oil 42.0 g Water 14.0 g Salt 0.5 g
  • 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. 20 ° C
  • soybean salad oil and salted egg yolk were combined and stirred under reduced pressure to obtain mayonnaise.
  • the pentacyclic triterpenes, their physiologically acceptable salts and their derivatives have an inhibitory effect on vascular smooth muscle cell proliferation and / or vascular smooth muscle cell migration.

Abstract

L'invention concerne un aliment ou une boisson pour des maladies ou des troubles vasculaires, contenant en tant que principe actif un composé sélectionné dans le groupe contenant des triterpènes pentacycliques, des sels de ces composés physiologiquement acceptables, et des dérivés de ces composés; ainsi qu'une matière première pour ledit aliment ou ladite boisson.
PCT/JP2002/003188 2001-03-30 2002-03-29 Aliment ou boisson pour maladie ou trouble vasculaire WO2002078468A1 (fr)

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WO2005027891A1 (fr) * 2003-09-22 2005-03-31 Use-Techno Corporation Accelerateur de secretion d'insuline de base
JPWO2004064818A1 (ja) * 2003-01-17 2006-05-18 麒麟麦酒株式会社 血圧降下剤および血管柔軟性改善剤並びにこれらの機能が付与された食品
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
JP2008239498A (ja) * 2007-03-24 2008-10-09 Shinshu Univ 発芽発酵ソバからａｃｅ阻害活性画分を分画する方法
JP2020533377A (ja) * 2017-09-13 2020-11-19 エミオン インコーポレイテッドＥｍｍｙｏｎ， Ｉｎｃ． ウルソール酸モルホリン塩及びジエタノールアミン塩

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JP5892928B2 (ja) 2009-06-12 2016-03-23 ジェネレックス ファーマシューティカルズ インコーポレイテッド 赤血球凝固の予防及び治療のための組成物並びに方法
CN102232956A (zh) * 2010-03-05 2011-11-09 中国科学院上海生命科学研究院 一种防治代谢性疾病的化合物及其用途
JP6147954B2 (ja) 2011-05-10 2017-06-14 丸善製薬株式会社 Ｔｉｅ２活性化剤、血管の成熟化剤、血管の正常化剤、及び血管の安定化剤

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Publication number Priority date Publication date Assignee Title
WO2003057224A1 (fr) * 2001-12-28 2003-07-17 The Nisshin Oillio, Ltd. Inducteur d'apoptose
JPWO2004064818A1 (ja) * 2003-01-17 2006-05-18 麒麟麦酒株式会社 血圧降下剤および血管柔軟性改善剤並びにこれらの機能が付与された食品
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
JP4688502B2 (ja) * 2003-04-22 2011-05-25 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
WO2005027892A1 (fr) * 2003-09-22 2005-03-31 Use-Techno Corporation Stimulateur de la sécrétion d'insuline précoce
JP2008239498A (ja) * 2007-03-24 2008-10-09 Shinshu Univ 発芽発酵ソバからａｃｅ阻害活性画分を分画する方法
JP2020533377A (ja) * 2017-09-13 2020-11-19 エミオン インコーポレイテッドＥｍｍｙｏｎ， Ｉｎｃ． ウルソール酸モルホリン塩及びジエタノールアミン塩

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