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WO2002078685A1 - Medicaments pour une lesion vasculaire - Google Patents

Medicaments pour une lesion vasculaire Download PDF

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Publication number
WO2002078685A1
WO2002078685A1 PCT/JP2002/003189 JP0203189W WO02078685A1 WO 2002078685 A1 WO2002078685 A1 WO 2002078685A1 JP 0203189 W JP0203189 W JP 0203189W WO 02078685 A1 WO02078685 A1 WO 02078685A1
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WO
WIPO (PCT)
Prior art keywords
acid
mass
physiologically acceptable
erythrodiol
derivatives
Prior art date
Application number
PCT/JP2002/003189
Other languages
English (en)
Japanese (ja)
Inventor
Hisami Shinohara
Gou Shinohara
Noriyasu Kuno
Original Assignee
The Nisshin_Oillio, Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Nisshin_Oillio, Ltd. filed Critical The Nisshin_Oillio, Ltd.
Priority to JP2002576951A priority Critical patent/JPWO2002078685A1/ja
Publication of WO2002078685A1 publication Critical patent/WO2002078685A1/fr

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Classifications

    • 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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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

  • the present invention relates to a method for treating vascular smooth muscle cell proliferation and / or vascular smooth muscle cell migration, intimal hyperplasia and arteriosclerosis and other cell proliferative vascular lesions, arteriosclerosis and percutaneous coronary angioplasty by oral and parenteral administration.
  • the present invention relates to an agent for a disease which exerts an effect of prevention and / or treatment for a vascular disorder disease such as restenosis later.
  • 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 there are cases where stenosis occurs again after PTCA.
  • This restenosis site is known to be a fibrous intimal thickening mainly composed of vascular smooth muscle cells.
  • hypertrophy of S which occurs as a result of proliferation of vascular smooth muscle cells, migration to the intima, and matrix deposition, is a major cause of atherosclerotic disease, hypertension, ischemic heart disease, and cerebrovascular disease. It is a factor.
  • vascular stenosis after transplantation of organs such as the heart, liver, kidney, and blood vessels also involves the proliferation of vascular smooth muscle cells.
  • Antithrombotic drugs and vasodilators are mainly used as treatments for angina pectoris and myocardial infarction, but narrowing of the vascular lumen and vascularization caused by restenosis and arteriosclerosis after PTCA are performed.
  • Treatment of atherosclerotic disease, ischemic heart disease and cerebrovascular disease involving vascular smooth muscle cell proliferation has so far been limited. Therefore, a drug capable of preventing or treating cell proliferative vascular lesions such as intimal hyperplasia and arteriosclerosis, which cause narrowing of the blood vessel lumen, has been desired.
  • Triterpenes are generally pentacyclic compounds consisting of six isoprene units, each having basically 30 carbon atoms, but undergoing transition, oxidation, elimination, or alkylation during biosynthesis, resulting in a change in carbon number Things are also included.
  • anti-inflammatory effects anti-carcinogenic promo-Yuichi effects (Journal of the Japan Oil Chemists' Society, 49, 571, 2000) are generally known.
  • persorbic acid and oleanolic acid are known to have an anti-hyperlipidemic effect, and ursolic acid also has an effect on atherosclerosis associated with hyperlipidemia. It is also known to have (Chemical Abstracts, 91, 49279 r. 5 1981, or Farmacology and Toks ikology, 45, 66—70, 1982). However, maslinic acid, erythrodiol, ursolic acid, ebaol, vertulinic acid, perrin, their physiologically acceptable salts and their derivatives have an effect on vascular smooth muscle cells. Until then, it was completely unknown. Disclosure of the invention
  • the present invention suppresses vascular smooth muscle cell proliferation and migration, and prevents and / or treats cell proliferative vascular lesions such as hypertrophy and arteriosclerosis, and vascular disorders such as arteriosclerosis and restenosis after PTCA. Therefore, an object of the present invention is to provide an agent for a vascular disorder having a very excellent effect on these.
  • the present inventors have conducted intensive studies in order to achieve the above object, and have found that maslinic acid, erythrodiol, ursolic acid, vaoyl, benzoic acid, pelin, and physiologically acceptable salts thereof And one or more selected from the group consisting of the following compounds: a vascular smooth muscle cell proliferation inhibitory effect, a vascular smooth muscle cell migration inhibitory effect, an anti-cell proliferative vascular lesion effect, an anti-vascular disorder disease effect, etc.
  • the present invention relates to one kind selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, berylin, physiologically acceptable salts thereof and derivatives thereof.
  • a vascular smooth muscle cell proliferation inhibitor comprising two or more as active ingredients, and is selected from the group consisting of maslinic acid, ursolic acid, and physiologically acceptable salts thereof, and derivatives thereof.
  • Species or two It relates to a vascular smooth muscle cell migration inhibitor containing the above as an active ingredient.
  • the present invention relates to one or more selected from the group consisting of maslinic acid, erythrodiol, persolic acid, baubaol, veric acid, perrin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to an anti-cell proliferative vascular lesion agent contained as an active ingredient, and preferably to an anti-cell proliferative vascular lesion agent 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-intimal thickening agent wherein the cell proliferative vascular lesion is intimal hyperplasia, and more preferably to an anti-arterial scleroderma wherein the cell proliferative vascular lesion is arteriosclerosis.
  • the present invention relates to one or more selected from the group consisting of maslinic acid, erythrodiol, persolic acid, benzoyl, veric acid, perrin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to an agent for a vascular disorder in which the vascular disorder is caused by a cell proliferative vascular lesion, preferably an anti-vascular agent in which the vascular disorder is arteriosclerosis.
  • the present invention relates to an agent for arteriosclerosis, preferably to an agent for anti-restenosis after PTCA, wherein the vascular disorder is restenosis after PTCA.
  • the present invention relates to one or more selected from the group consisting of maslinic acid, erythrodiol, persolic acid, baol, veric acid, veline, physiologically acceptable salts thereof and derivatives thereof, One or two selected from the group consisting of maslinic acid, ursolic acid and their physiologically acceptable salts, or derivatives thereof, for use in producing a vascular smooth muscle cell proliferation inhibitor More than one type of use for producing a vascular smooth muscle cell migration inhibitor.
  • the present invention relates to one or more selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, ellulin, physiologically acceptable salts thereof and derivatives thereof.
  • Preferred for use in the manufacture of two or more anti-cell proliferative vascular lesion agents, preferably for use in the manufacture of an anti-intimal thickening agent The present invention relates to a use for producing an anti-atherosclerotic agent.
  • the present invention relates to one or two kinds selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, perrin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to the use for producing an agent for a vascular disorder disease, preferably to the use for producing an anti-atherosclerosis agent, and preferably to the use for producing an anti-restenosis agent after PTCA.
  • the present invention relates to one or more selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, veline, physiologically acceptable salts thereof, and derivatives thereof.
  • a vascular smooth muscle cell growth inhibitor raw material and a method for using the same further comprising one selected from the group consisting of maslinic acid, ursolic acid, and physiologically acceptable salts thereof, and derivatives thereof
  • a vascular smooth muscle cell migration inhibitor raw material containing two or more kinds and a method of using the same.
  • the present invention provides one or two kinds selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, verin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a raw material for an anti-cell proliferative vascular lesion agent and a method for using the same, preferably to a raw material for an anti-intimal thickener and a method for using the same, and preferably to a raw material for an anti-atherosclerotic agent and a method for using the same.
  • the present invention relates to one or two kinds selected from the group consisting of maslinic acid, erythrodiol, persolic acid, benzoyl, berylic acid, berlin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a raw material for a vascular disorder containing the above, preferably to a raw material for an anti-atherosclerotic agent and a method for using the same, and preferably to a raw material for an anti-restenotic agent after PTCA and a method for using the same.
  • the present invention also relates to one or more kinds selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, ellulin, physiologically acceptable salts thereof and derivatives thereof.
  • Vascular smooth muscle cells containing as an active ingredient The present invention relates to a prophylactic or therapeutic agent for a disease involving a pathology or pathology involving proliferation or vascular smooth muscle cell migration.
  • the present invention also relates to one or two members selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, veline, physiologically acceptable salts thereof, and derivatives thereof.
  • Intima thickening arteriosclerosis, cell proliferative vascular lesions, coronary atherosclerosis, abdominal atherosclerosis, obstructive atherosclerosis, renal arteriosclerosis, facial arteriosclerosis, fundus arteriosclerosis containing the above as active ingredients , Cerebral arteriosclerosis, arteriosclerosis, percutaneous coronary artery 1) Restenosis after myoplasty, myocardial infarction, angina pectoris, ischemic heart disease, cerebral infarction, preventive or therapeutic agent for stroke or cerebrovascular disease About.
  • the present invention also provides a vascular smooth muscle cell proliferation inhibitor, a vascular smooth muscle migration inhibitor, an anti-cell proliferative vascular lesion agent or a vascular agent, comprising as an active ingredient an extract obtained by treating a defatted product of Olive with an ethanol solution.
  • the present invention relates to an agent for a disorder.
  • the present invention relates to one or more members selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, benzoyl, diphosphoric acid, berylin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a vascular smooth muscle cell proliferation inhibitor comprising two or more active ingredients. Of these, maslinic acid, erythrodiol, ursolic acid and derivatives thereof are preferred.
  • the present invention also relates to a vascular smooth muscle containing, as an active ingredient, one or more selected from the group consisting of maslinic acid, ursolic acid, and physiologically acceptable salts thereof, and derivatives thereof. It relates to a cell migration inhibitor.
  • maslinic acid ursolic acid and derivatives thereof are preferred.
  • These substances are pentacyclic compounds among the triterpenes composed of six isoprene units, and are a group of substances that are abundant in various plants in nature. These can be naturally obtained by extracting from plants, and some of them are artificially obtained. Some are synthesized and already sold as reagents and the like, and any of them can be suitably used. These can be used in both oral and parenteral forms.
  • the content thereof is not particularly limited It can be adjusted as appropriate 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.
  • the concentration is preferably high. Although not particularly limited, it is preferably 0.1% by mass or more, more preferably 0.1 to 99.99% by mass, still more preferably 1 to 99.99% by mass, and further preferably 10 to 99.99% by mass. %, More preferably 30 to 99.99% by mass, further preferably 50 to 99.99% by mass, further preferably 70 to 99.99% by mass, and further preferably 90 to 99.99% by mass.
  • the present invention provides one or two kinds selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, verin, physiologically acceptable salts thereof and derivatives thereof.
  • An anti-cell proliferative vascular lesion containing the above as an active ingredient preferably, 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-intimal thickening agent wherein the cell proliferative vascular lesion is intimal hyperplasia, and more preferably to an anti-atherosclerotic agent wherein the cell proliferative vascular lesion is atherosclerosis.
  • Preferred active ingredients are maslinic acid, erythrodiol, ursolic acid and derivatives thereof. These can be used in both oral and non-oral forms. They have anti-cell proliferative vascular pathological effects, such as intimal hyperplasia inhibitory effects and / or anti-atherosclerotic effects, and these effects can be evaluated in animal and clinical assays.
  • the term “containing as an active ingredient” means that it is contained to such an extent that an anti-cell proliferative vascular lesion effect, for example, an intimal hyperplasia inhibitory effect and / or an anti-atherosclerotic effect is exhibited, but the content is particularly limited. It can 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.
  • the concentration is preferably high. Although not particularly limited, preferably 0.1% by mass or more, more preferably 0.1 to 99.99% by mass, More preferably 1 to 99.99% by mass, more preferably 10 to 99.99% by mass, more preferably 30 to 99.99% by mass, further preferably 50 to 99.99% by mass, and still more preferably 70 to 99.99% by mass. 99.99% by mass, more preferably 90 to 99.99% by mass.
  • the preparation preferably contains one or more selected from pharmacologically acceptable bases and the like similar to the above-mentioned inhibitors.
  • the present invention provides an effective use of one or more selected from the group consisting of maslinic acid, erythrodiol, persolic acid, basol, veric acid, veline, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to an agent for a vascular disorder disease contained as a component, and preferably to an agent for a vascular disorder disease in which the vascular disorder disease is caused by a cell proliferative vascular lesion.
  • the present invention relates to an agent for arteriosclerosis, and preferably to an agent for anti-restenosis after PTCA wherein the vascular disorder is restenosis after PTCA.
  • These can be used in both oral and parenteral forms. They have anti-vascular disease effects, such as anti-atherosclerotic and / or anti-restenotic effects, and these effects can be evaluated in animal and clinical assays.
  • the term “containing as an active ingredient” means that it 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, but its content is particularly limited. Adjustment can be made 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.
  • the preparation preferably contains one or more selected from pharmacologically acceptable bases and the like similar to the above-mentioned inhibitors.
  • the present invention relates to one or more selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, veline, physiologically acceptable salts thereof, and derivatives thereof.
  • a vascular smooth muscle cell growth inhibitor raw material and a method for using the same further comprising one selected from the group consisting of maslinic acid, ursolic acid, and physiologically acceptable salts thereof, and derivatives thereof
  • a vascular smooth muscle cell migration inhibitor raw material containing two or more kinds and a method of using the same. Any of those obtained from natural plants and those obtained artificially can be suitably used.
  • the present invention provides one or two kinds selected from the group consisting of maslinic acid, erythrodiol, persolic acid, benzoyl, berylic acid, berylin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a raw material for an anti-cell proliferative vascular lesion agent and a method for using the same, preferably to a raw material for an anti-intimal thickener and a method for using the same, and preferably to a raw material for an anti-atherosclerotic agent and a method for using the same.
  • any of those obtained from natural plants and those obtained artificially can be suitably used.
  • the present invention provides one or two kinds selected from the group consisting of maslinic acid, erythrodiol, persolic acid, benzoyl, berylic acid, berylin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a raw material for an anti-atherosclerosis agent and a method for using the same, and preferably to a raw material for an anti-restenotic agent after PTCA and a method for using the same.
  • any of those obtained from natural plants and those obtained artificially can be suitably used.
  • the present invention relates to one or more selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, benulinic acid, veline, physiologically acceptable salts thereof and derivatives thereof.
  • An anti-cell proliferative vascular lesion agent and / or anti-artery such as a vascular smooth muscle cell proliferation inhibitor and / or a vascular smooth muscle migration inhibitor and / or an anti-intimal thickening agent which contains Sclerosis agents ⁇
  • Agents for vascular disorders such as anti-restenosis agents after PTCA.
  • These substances are a kind of triterbene, and are pentacyclic compounds consisting of six isoprene units. They can be obtained from natural plants or artificially, and commercially available products are suitable. Can be used.
  • the term “containing as an active ingredient” means that it is contained to such an extent that the effect of each purpose is exhibited.
  • the present invention relates to a vascular smooth muscle cell containing maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, berylin, a physiologically acceptable salt thereof and a derivative thereof as an active ingredient.
  • the present invention relates to a preventive or therapeutic agent for a disease associated with a pathology or pathology involving proliferation or vascular smooth muscle cell migration.
  • prophylactic or therapeutic agents containing maslinic acid, etrodiol, persolic acid and derivatives thereof are preferred.
  • the present invention relates to an intimal hyperplasia containing maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin, a physiologically acceptable salt thereof and a derivative thereof as an active ingredient.
  • Arteriosclerosis cell proliferative vascular lesions, coronary arteriosclerosis, abdominal aortic sclerosis, obstructive arteriosclerosis, sclerosclerosis, carotid artery sclerosis, fundus arteriosclerosis, cerebral arteriosclerosis, arteriosclerosis , Percutaneous coronary angioplasty restenosis, myocardial infarction, angina pectoris, ischemic heart disease, cerebral infarction, stroke or cerebrovascular disease I do.
  • a prophylactic or therapeutic agent containing maslinic acid, erythrodiol, ursolic acid and derivatives thereof as an active ingredient is preferred.
  • the physiologically acceptable salt is, in particular, a salt derived from the carboxyl group of a pentacyclic triterpene acid (partial structure: —C 0 OX; X represents any anionic substance), and the present invention. And those originally contained in isolates from natural products.
  • the salt is not particularly limited as long as it is a salt usually used in foods and drinks or pharmaceutical compositions, and examples thereof include alkali metal salts such as sodium, potassium and lithium, calcium, magnesium, nordium, and the like.
  • Alkaline earth metal salts such as zinc, ammonia, methylamine, dimethylamine, trimethylamine, ethylamine, getylamine, triethylamine, propylamine, alkylamine salts such as butylamine, tetrabutylamine, pentylamine, hexylamine, ethanolamine, and gelamine.
  • alkanolamine salts such as ethanolamine, triethanolamine, propanolamine, dipropanolamine, isopropanolamine, diisopropanolamine, and other organic amines such as piperazine and piperidine , Lysine, arginine, histidine, salts such as basic Amino acid salts of tryptophan and the like.
  • alkali metal salts alkylamine salts, alkanolamine salts and basic amino acid salts are preferred.
  • these salts are more soluble in water than the triterpenes from which they are derived, and thus are preferred in the present invention, particularly when applied to aqueous agents for vascular disorders and the like.
  • 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 are particularly preferred.
  • oil-based vascular disorders are used in the present invention because the derivative which is used is more lipophilic than maslinic acid, erythrodiol, persolic acid, basol, verpulinic acid, and verinin.
  • Glycosides are preferable when applied to drugs for diseases, etc., and have more water-solubility than their original maslinic acid, erythrodiol, ursolic acid, evaoyl, benulinic acid, and veline. Therefore, in the present invention, it is particularly preferable when applied to an aqueous agent for a vascular disorder or the like.
  • 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; I or any hydrocarbon functional group). That is, the derivatives of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, and verin having an alcohol ester group in the present invention are, in particular, those derivatives that can be formed from the carboxyl group and alcohols. Is shown.
  • alcohols at this time there are no particular restrictions on the alcohols at this time, but for example, methanol, ethanol, n-propanol, isopropanol, aryl alcohol, n-butanol, sec-butanol, tert-butanol, ethylene glycol , Trimethylsilyl alcohol, triethylsilyl alcohol, phenol, benzyl alcohol, saccharides and the like. Among them, ethanol, triethylsilyl alcohol, methanol, n-propanol, isopropanol or triethanol Derivatives formed from methylsilyl alcohol are preferred.
  • 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, in the present invention, the derivative having a fatty acid ester group, such as maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, and berylin, particularly refers to a derivative that can be formed from its hydroxyl group and fatty acids.
  • the fatty acids at this time are not particularly limited, but include, for example, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, pivalic acid, caproic acid, caprylic acid, capric acid, pendecanoic acid, and lauric acid.
  • Acid myristic acid, palmitic acid, norrethleic acid, stearic acid, oleic acid, elaidic acid, paxenoic acid, linoleic acid, linoleic acid, linolenic acid, alinolenic acid, arachidic acid, arachidonic acid, eicosapentaenoic acid, Examples include behenic acid, docosahexanoic acid, lignoceric acid, cerotic acid, montanic acid, and melicic acid. Among them, acetic acid, acetic anhydride, cabronic acid, cabrylic acid, acetic acid, lauric acid, myristic acid, palmitic acid, and phenol.
  • An alkoxy group refers to a functional group formed as a result of a dehydration reaction between a general hydroxyl group and an alcohol (partial structure: —OR; R represents an arbitrary hydrocarbon-based functional group).
  • the derivative having an alkoxy group of maslinic acid, erythrodiol, persolic acid, divinyl, berylic acid, and berylin particularly refers to a derivative that can be formed from its hydroxyl group and alcohols.
  • alcohols There are no particular restrictions on the alcohols at this time, but examples include methanol, ethanol, I-propanol, isopropanol, aryl alcohol, n-butanol, sec-butanol, tert-butanol, and ethylene glycol.
  • 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: —CH 2 OR; R represents any hydrocarbon functional group) Shown). That is, the derivative having an alkoxymethyl group of maslinic acid, erythrodiol, ursolic acid, ebaol, vertulinic acid, and verin in the present invention is, in particular, a compound which can be formed from its hydroxymethyl group and alcohols. Derivatives are shown.
  • the alcohols at this time there are no particular restrictions on the alcohols at this time, but for example, methanol, ethanol, n-propanol, isopropanol, aryl alcohol, n-butanol, sec-butanol, tert-butanol, ethylene glycol , Trimethylsilyl alcohol, triethylsilyl alcohol, phenol, benzyl alcohol, saccharides and the like. Of these, the derivatives formed from ethanol, triethylsilyl alcohol, methanol, n-propanol, isopropanol or trimethylsilyl alcohol are preferred.
  • the glycoside in the present invention includes, among the derivatives having an alcohol ester group, the derivative having an alkoxy group, and the derivative having an alkoxymethyl group, particularly, maslinic acid, erythrodiol, ursolic acid, ebaol , Derivatic acid, and derivatives that can be formed from carboxyl, hydroxyl, and hydroxymethyl groups of berylin and saccharides (partial structure: one COOR, —OR, —CH20R; R represents any saccharide) .
  • saccharides there are no particular restrictions on the saccharides at this time, for example, glucose, mannose, galactose, fructose, xylose, arabinose, fucose, rhamnose, glucosamine, galactosamine, dalc baltic acid and the like. either will do.
  • These glycosides may be monosaccharides or various sugars such as disaccharides. Any combination of oligosaccharides may be used. Some of these usually occur naturally and are known collectively as saponins, but any of these may be used in the present invention.
  • 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 agent for a vascular disorder of the present invention, the origin of these substances is not limited, Any of those obtained from natural raw materials, artificially synthesized, and commercially available products 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 is a kind of oleanane triterpene and has a structure represented by the chemical formula (1), and is known to have an anti-inflammatory effect and an anti-histamine effect. In nature, it is known to be present in olive oil, hops, hearts, pomegranates, foliage, sage, and squid.
  • the origin of maslinic acid, its physiologically acceptable salts and derivatives is not limited, and it is obtained from natural raw materials, artificially synthesized, and commercially available.
  • any of these can be used, but in consideration of oral use, for example, those obtained from natural raw materials such as olive, hops, hazelnut, pomegranate, chickpea, sage, and naume are preferable.
  • Masphosphoric acid and / or a physiologically acceptable salt thereof obtained from Olive are very preferable in terms of raw material supply and content.
  • 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 an olive plant and / or a product obtained in a process of producing olive oil and / or olive oil.
  • 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 1C ⁇ H in the chemical formula (1), 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.
  • Examples of the derivative of maslinic acid include, for example, those in which any one of the derivatives is derivatized, such as methyl maslinate, ethyl maslinate, n-propyl maslinate, isopropyl maslinate, and maslinic acid n-Butyl ester, trimethylsilyl masphosphate, triethylsilyl masphosphate, mono-/?-D-glucoviranosyl ester, mono- / mass-phosphate /?-D-galactopyranosyl ester, 3-0-acetyl-mass Phosphoric acid, 3-0-propionyl-massic acid, 3--1-butylyl-massic acid, 3-0-no ⁇ ; relyl-massic acid, 3-0-force prill-massic acid, 3-0-lauryl-mass Phosphoric acid, 3-0-myristyl-massic acid, 3-0-
  • D Glucobilanosyl monophosphate
  • 3— ⁇ 3—D Galactopyranosyl monophosphate
  • 3—0 — / — D Glucuronoviranosyl monophosphate
  • D-glucoviranosyl-massic acid 2-0 — ⁇ — D— Galactopyranosyl-massic acid, 2-0-?-D-glucuronopyranosyl-massic acid, and the like.
  • ethyl masphosphate, triethyl masyl phosphate, 3-0-acetyl-maslinic acid, 2-0-acetyl-massic acid, 2-0-triethylsilyl-massic acid, 3-0-stearoyl-massic acid And 2-0-stearoyl-maslinic acid are preferred.
  • maslinic acid or 2,3-0-diacetyl, 2,3- ⁇ ditriethylsilyl and 2,3-distearoyl of the above-mentioned preferable maslinic acid esters are preferable.
  • 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 and has a structure as shown in chemical formula (2). Its effect has been anti-inflammatory effect (Plant a. Med. VOL. 61, No. 2). , 182-185 19 95). In nature, it is known to be present in oribu, sunflower, calendula, gum arabic, kodokutan, and Nagabakakonoki. In the agent for a vascular disorder of the present invention, the origin of erythrodiol or a derivative thereof is not limited, and any one obtained from natural raw materials, artificially synthesized, or a commercially available product may be used.
  • those obtained from natural raw materials such as olive oil, sunflower, Kinsen power, gum arabic, copoxytan, and Nagakakonoki are preferable.
  • an olive is preferred, and specifically, an olive plant and / or a product obtained from a product obtained in an olive oil production process is preferred.
  • 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-propionyl-erythrodiol, 3-0 -Butyrrhyl erythrodiol, 3-0-valeryl-erythrodiol, 3-0-capryluyl-erythrodiol, 3-0-lauryl-erythrodiol, 3-0-myristyl-erythrodiol, 3-0-palmityl-erythrodiol, 3-0-palmi Toleil-erythrodiol, 3- ⁇ —stearyl monoerythrodiol, 3-0—stearoyl monoerythrodiol, 3-0—oleylerythrodiol, 3-0—bacelylerythrodiol, 3-0—linoleyl monoerythrodiol , 3-0—linolenyl,
  • D galactopyranosyl-erythrodiol
  • 28—0 — /? D—glucuronoviranosyl-erythrodiol and the like.
  • 3--1-acetyl-erythrodiol and 28-0-acetyl-erythrodiol are preferred.
  • two or more of the derivatives having a derivable position and type may be derivatized.
  • 3,28-0-diacetyl-erythrodiol can be mentioned.
  • glycosides are listed as the glycosides, but naturally, disaccharides or more oligosaccharides selected from the group consisting of various saccharides may be used.
  • Both persolic acid and baol are a kind of ursan triterpenes and are known to be present in various plants.
  • the physiologically acceptable salt and the derivative thereof are the same as described above.
  • ursolic acid, ebaol, a physiologically acceptable salt thereof, or a derivative thereof is used in the agent for treating a vascular disorder of the present invention, the origin of these substances is limited. Not Any of those obtained from natural raw materials, artificially synthesized, and commercially available products can be used, but natural products are preferably used in consideration of oral use.
  • Ursolic acid (urs 01 ic acid) is a kind of ursane triterpene, a compound having the structure represented by the chemical formula (3). Antidiabetic effect, antihyperlipidemic effect (Jie Liu, J
  • the origin of ursolic acid, a physiologically acceptable salt thereof, or a derivative thereof is not limited, and those obtained from natural raw materials or artificially synthesized Any of those prepared and commercially available products can be used, but in consideration of oral use, products obtained from natural raw materials such as apples, cherries, and radish 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 persoleate, ammonium persoleate, dimethylammonium ursoleate, persolic acid Calcium and magnesium ursolic acid.
  • any one of which is derivatized such as methyl ursoluate, ethyl ethyl ursorate, n-propyl ursoleate, isopropyl persoleate, N-Butyl uric acid ester, trimethylsilyl ursoic acid ester, triethylsilyl ursoic acid ester, 1 /?-Persolic acid D-glucoviranosyl ester, 1 /?-Ursolic acid D-galact Toviranosyl ester, 3-0-acetyl-ursolic acid, 3-0_propionyl-ursolic acid, 3-0-butyryl-ursolic acid, 3-0-valeryl persolic acid, 3-0 —Force prill—ursolic acid, 3—0—lauryl-ursolic acid, 3-0—myristyl—persolic acid, 3—0 palmityl-persolic acid Sul
  • Baol (uvao 1) is a kind of ursan triterpene and has a structure similar to that of chemical formula (4). 2, 182-1 85 1995), deglycerophosphate It is known that it has a hydrogenase inhibitory effect (Japanese Patent Application Laid-Open No. Hei 9-7167249). Naturally, it is known to be present in Oliveb, Dewaulushi, Sage, Gum arabic and Rybupte.
  • the origin of baioru or a derivative thereof is not limited, and any of a product obtained from a natural raw material, an artificially synthesized product, a commercial product, and the like may be used.
  • those obtained from natural raw materials such as olive oil, beetle, sage, gum arabic and rypte are preferred.
  • olive is preferable, and specifically, olive plants and those obtained from the product obtained in the Z or olive oil production process are preferable.
  • the derivative is not limited to the following, but, for example, assuming that any one of the derivatives is inducted, 3-0-acetyl-baol, 3-0-propio-l-ubaol, 3-0-butyryl —Baobaol, 3—0—Valeryl—Baobaol, 3—0—Priorubaol, 3—0—Lauryl—Baobaal, 3—0—Myristyl Baobal, 3—0—Palmichil—Baobal, 3-0—Palmi Tole Reubaol, 3-0—Stearyl Reubaol, 3-0—Stair mouth, Reubaol, 3—0—Leilaubaol, 3—0—Baxenil—Bauba Oars, 3-0—Linoleil-Baol, 3-0—Linolenyl-Baol, 3-0—Arakijiru-Baol, 3-0—Arakdon
  • beryric acid, beryulin, a physiologically acceptable salt thereof, or a derivative thereof is used in the agent for a vascular disorder of the present invention
  • the origin of these substances is not limited, and natural Any of those obtained from raw materials, artificially synthesized, commercially available products, etc. can be used, but natural products are preferably used in consideration of oral use.
  • Betulinic acid (betul inic acid) is a kind of lupine triterpene and has a structure like chemical formula (5). Its effects have been anticancer, anti-inflammatory and wound healing effects. (Japanese Patent Publication No. 4-26623), alcohol absorption suppressing effect (JP-A-7-53385), hair growth promoting effect (JP-A-9-157139), and the like. It is known in nature that it is present in free form in sempuri, cinnamon, bud peel, olive, etc., and as saponin in chixin ginseng, carrot, sugar beet and the like.
  • the origin of phosphoric acid, a physiologically acceptable salt thereof, or a derivative thereof is not limited, and can be obtained from a natural raw material or artificially synthesized.
  • natural raw materials such as sempuri, butterfly, grape, olive, thixin ginseng, carrot, sugar beet, etc. Is preferred.
  • those obtained from olive plants are preferred, and specifically those obtained from products obtained in the olive plant and / or olive oil production process.
  • 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 salts of beryric acid include sodium perphosphate, potassium perphosphate, ammonium perphosphate, dimethyl ammonium perate, Calcium berinate, magnesium berinate and the like can be mentioned. Of these, sodium perphosphate and potassium perphosphate are preferred.
  • Derivatives of verpulinic acid include, for example, those in which any one of the derivatives is derivatized, such as methyl verpulinate, ethyl ester vertate, n-propyl vertate, isopropyl vertate, Berylic acid n-butyl ester, trimethylsilyl berylate, triethylsilyl berylate, 1 /?-1 d-glucoviranosyl ester, 1 /?-1 berylic acid D-galactopyranosyl ester, 3- 0-acetyl-berpulinic acid, 3-0-propionyl-ruberic acid, 3-0-butylyl-ruberic acid, 3-0-valeryl monoberic acid, 3-0-capryruberic acid, 3-0- Lauryl monobernic acid, 3-0-myristyl-verulic acid, 3-0-palmityl monobernic acid, 3-palmyl palmitoreyl Phosphoric acid, 3- ⁇
  • ethyl berylate is preferred.
  • only one derivative has been derivatized.
  • two or more of the derivatives having derivable positions and types may be derivatized.
  • only glycosides are listed as the glycosides, but naturally, disaccharides or more oligosaccharides selected from the group consisting of various saccharides may be used.
  • Betulin is a kind of lupine triterpene and has a structure similar to that of chemical formula (6).
  • the effect has been the inhibitory effect on bioprotein denaturation (Japanese Patent Application Laid-Open No. 9-67253), The inhibitory effect of mutated dehydrogenase (JP-A-9-67249), lipase inhibitory effect (JP-A-10-265328), liver disease prevention effect (JP-A-11-209275), etc. It is known to have. In nature, it is known to be present on the bark of birch and the like.
  • the origin of perrin or a derivative thereof is not limited, and any of those obtained from natural raw materials, artificially synthesized, and commercially available products can be used. Considering oral use, those obtained from natural raw materials such as birch bark are preferred. Chemical formula (6)
  • physiologically acceptable salts and derivatives of beverin are the same as described above.
  • the derivative is not limited to the following, but, for example, assuming that one of the derivatives is inducted, 3-0-acetyl-verulin, 3-0-propionylruberin, 3-0- Butyriluverin, 3-0—Valeryl monoberin, 3-0—Capryluberin, 3-0—Lauryl monoberin, 3—0—Myristyl monoberin, 3—0—Parmityl monoberin, 3 _ 0—Palmi Toray Leverin, 3—0—Stearyl Leverin, 3—Pesterolyl Leverin, 3—0—Oreyl Leverin, 3-0—Vaxen Leverin, 3—Linoleil , 3-0-linolenyluperin, 3-0-arachidylupperin, 3- ⁇ _ arachidonylperin, 3-0- ⁇ enilylperin, 28-0-acetylbeperin , 2 8— 0—propione Perrin,
  • glycosides are listed as glycosides, naturally, disaccharides or more oligosaccharides selected from the group consisting of various saccharides may be used.
  • the present invention relates to one or more kinds selected from the group consisting of the above-mentioned maslinic acid, erythrodiol, persolic acid, baol, vertulinic acid, pearlin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a vascular smooth muscle cell proliferation inhibitor contained as an active ingredient.
  • containing as an active ingredient means that the compound is contained to such an extent that the effect of suppressing vascular smooth muscle cell proliferation 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 vascular smooth muscle cell proliferation inhibitor of the present invention is used as a prophylactic / therapeutic agent particularly for the increase of arteriosclerosis. Use as a prophylactic agent means to migrate to the intima and It is intended to suppress the proliferation of vascular smooth muscle cells and to prevent atherosclerosis from occurring.
  • the use as a therapeutic agent means that total vascular smooth muscle cells are inhibited by suppressing further proliferation of vascular smooth muscle cells already existing in the intima or by rapidly reducing the number of proliferated vascular smooth muscle cells. It is used for the purpose of reducing the increase of atherosclerotic lesions and preventing the rupture of atherosclerotic lesions. Therefore, the present invention also relates to one or two members selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, vertulinic acid, veline, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a prophylactic or therapeutic agent for a disease associated with a pathology or pathology involving vascular smooth muscle cell proliferation, containing the above as an active ingredient.
  • 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 (Japanese Patent Application Laid-Open No. 5-566976), and screening is easy. The feature is that rapid and large animal sacrifice can be avoided.
  • the presence or absence of a growth inhibitory effect is examined by using a reagent that generates a fluorescent substance by the redox ability of cultured vascular smooth muscle cells and determining the amount of the fluorescent substance generated by the intensity of the fluorescence intensity. are doing.
  • vascular smooth muscle cells present in the media of the arterial wall have a function of regulating blood flow by repeating contraction and relaxation, and are structurally rich in fiber components including hiactin.
  • 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 type 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 single layer is formed uniformly.
  • vascular smooth muscle cell proliferation inhibitory effect when 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 activity of the cells is relatively suppressed, and the generated 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.
  • vascular smooth muscle of maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, berylin, their physiologically acceptable salts and their derivatives in the present invention Compared with the known anti-arteriosclerotic agent, tocopherol, the antiproliferative effect is, for example, about 10 to 14 times for maslinic acid, about 6 to 10 times for maslinic acid salt, and about 10 to 10 times for erythrodiol.
  • ursolic acid for about 6 to 10 times, ebaol for about 4 to 8 times, berylic acid for about 4 to 8 times, for berin, about 4 to 8 times, for maslin ester
  • maslinic acid, ursolic acid and their physiologically acceptable salts, or their derivatives have an inhibitory effect on vascular smooth muscle cell migration. That is, More specifically, vascular smoothing containing as an active ingredient one or more selected from the group consisting of maslinic acid, ursolic acid and their physiologically acceptable salts, or their derivatives It relates to a muscle cell migration inhibitor.
  • containing as an active ingredient means containing to the extent that the effect of inhibiting vascular smooth muscle cell migration is exhibited.
  • the vascular smooth muscle migration inhibitory effect is defined as a vascular smooth muscle cell derived from the media that has obtained a proliferation ability from a blood component that has deviated from a normal value due to vascular injury, hyperlipidemia, or the like.
  • Inhibition of migration ( migration) from the vascular media to the vascular intima or to the atherosclerotic lesion under the vascular endothelial cells according to the concentration gradient of the blood vessels, resulting in the migration of vascular smooth muscle cells. It can be expected to prevent the formation of atherosclerotic lesions by suppressing the occurrence of vascular smooth muscle cells, and to prevent the migration of vascular smooth muscle cells into the existing atherosclerotic lesions.
  • the vascular smooth muscle cell migration inhibitor of the present invention is intended to inhibit the migration of vascular smooth muscle cells from the media to the intima, and to prevent the formation of arteriosclerotic foci. It is used as a preventive against nest growth and the like.
  • the number of cells in which vascular smooth muscle cells have been activated by a migration factor and migrated toward a higher concentration of the migration factor is counted, and compared with a control group to determine the presence or absence of a migration inhibitory effect. Has been determined.
  • the present invention also relates to one or more members selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin, physiologically acceptable salts thereof, and derivatives thereof.
  • the present invention relates to a preventive or therapeutic agent for a disease involving vascular smooth muscle cell migration or a disease associated with a disease state, comprising two or more types as active ingredients.
  • the vascular smooth muscle cell migration inhibitory effect of maslinic acid, persolic acid and their physiologically acceptable salts or their derivatives 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 proliferating cultured vascular smooth muscle cell line derived from rat aorta. When the activating factor is activated, cells migrate to the higher concentration. On the other hand, when a substance having an inhibitory effect on vascular smooth muscle cell migration is present together with a migration factor, the number of cell migration decreases. From this relative degree of cell number, the effect of inhibiting vascular smooth muscle cell migration can be estimated.
  • maslinic acid is about 25 to 30 times
  • maslinic acid salt is about 25 to 30 times
  • ursolic acid is about 25 to 30 times.
  • urethyl monoethyl ester has a very high vascular smooth muscle cell migration inhibitory effect of about 24 to 27 times. That is, by containing maslinic acid, persolic acid and its physiologically acceptable salts, or derivatives thereof, it is possible to enjoy its very strong vascular smooth muscle cell migration inhibitory effect. In particular, they are very preferable because they also have a vascular smooth muscle cell proliferation inhibitory effect.
  • the present invention relates to one kind selected from the group consisting of maslinic acid, erythrodiol, persolic acid, benzoyl, berylic acid, berylin, a physiologically acceptable salt thereof, and a derivative thereof.
  • an anti-cell proliferative vascular lesion agent comprising two or more as active ingredients.
  • a cell proliferative vascular lesion is a vascular tissue site in which intimal thickening or arteriosclerosis has occurred due to migration and abnormal proliferation of vascular smooth muscle cells. It refers to atherosclerotic lesions such as sclerosis, carotid atherosclerosis, fundus atherosclerosis, and cerebral atherosclerosis, and restenosis after PCTA.
  • the anti-cell proliferative vascular lesion agent of the present invention particularly has an effect on intimal hypertrophy and atherosclerosis caused by vascular smooth muscle cell proliferation and / or vascular smooth muscle cell migration. It has the effect of preventing and / or treating intimal thickening and arteriosclerosis.
  • the present invention provides a method for producing a vascular lesion, wherein the cell proliferative vascular lesion is intimal hyperplasia, comprising maslinic acid, erythrodiol, ursolic acid, baobal, porulinic acid, veulin, a physiologically acceptable salt thereof, and
  • the present invention relates to an anti-intimal thickener containing one or more selected from the group consisting of derivatives thereof as an active ingredient.
  • containing as an active ingredient means that it is contained to such an extent that the effect of suppressing intimal hyperplasia is exhibited.
  • the effect of suppressing intimal hyperplasia means inhibiting the intimal hypertrophy of blood vessels due to migration and abnormal proliferation of vascular smooth muscle cells, and as a result, such as arteriosclerosis, myocardial infarction, heart failure, etc. It is expected to prevent and / or treat cerebrovascular diseases such as ischemic heart disease, cerebral infarction and stroke.
  • the effect of maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, berylin, their physiologically acceptable salts and their derivatives on the inner monthly hypertrophy was evaluated using animals. Shown by test method. In other words, physically exfoliating the endothelial cells of the artery causes inflammation in the site, and vascular smooth muscle cells migrate and proliferate in the intima at the site, thereby thickening the intima. In contrast, administration of a substance having an intimal hyperplasia inhibitory effect to animals suppresses hypertrophy. From this degree of suppression, the effect of suppressing intimal thickening can be estimated.
  • maslinic acid suppresses about 40 to 60%
  • maslinic acid salt suppresses about 35 to 55%
  • erythrodiol about 40 to 60% Inhibition, about 30-50% suppression in persolic acid, about 25-45% suppression in baioruol, about 15-35% suppression in berylic acid, about 15-35% in berylin It can be seen that it has a high inhibitory effect on intimal hyperplasia.
  • maslinic acid, erythrodiol, persor By containing luric acid, ebaol, berylic acid, berylin, their physiologically acceptable salts and their derivatives, they can enjoy a high inner hypertrophy control effect.
  • the present invention relates to the above-mentioned, wherein the cell proliferative vascular lesion is arterial sclerosis, maslinic acid, erythrodiol, ursolic acid, ebaol, vellic acid, vepulin, a physiologically acceptable salt thereof,
  • the present invention relates to an anti-atherosclerotic agent containing one or more selected from the group consisting of derivatives thereof as an active ingredient.
  • the anti-atherosclerotic agent of the present invention exhibits an anti-atherosclerotic effect when administered orally and / or parenterally.
  • the anti-atherosclerotic effect is intended to suppress the proliferation of vascular smooth muscle cells in atherosclerotic lesions and / or suppress the migration of proliferating vascular smooth muscle cells into arteriosclerotic lesions.
  • atherosclerosis is defined as vascular smooth muscle cells that have been transformed from a contractile type to a proliferative type, triggered by arterial endothelial damage, migrate from the media to the intima, and proliferate in the intima. It is thought to be caused by intimal thickening.
  • the anti-atherosclerotic agent of the present invention includes maslinic acid, erythrodiol, ursolic acid, baioru, beperin, which have a vascular smooth muscle cell proliferation inhibitory effect and / or a vascular smooth muscle cell migration inhibitory effect.
  • the anti-atherosclerotic agent of the present invention exerts its anti-atherosclerotic effect when ingested, improves or prevents ischemic heart disease, cerebral vascular disease, etc., and greatly increases the survival rate. It will contribute.
  • maslinic acid persolic acid and their physiologically acceptable salts or their derivatives are contained as active ingredients
  • an anti-atherosclerotic agent has a vascular smooth muscle cell proliferation inhibitory effect and a vascular smooth muscle cell migration inhibitory effect, and can be used as a powerful anti-atherosclerotic agent, and is very preferable.
  • the anti-atherosclerotic effects of maslinic acid, erythrodiol, persolic acid, baol, beric acid, berylin, their physiologically acceptable salts and their derivatives in the present invention were shown by test methods using animals. It is.
  • feeding a high cholesterol diet for a long time causes arteriosclerosis in the aorta.
  • administration of a substance having an anti-atherosclerotic effect to animals suppresses aortic sclerosis.
  • the anti-atherosclerotic effect can be estimated from this degree of suppression.
  • maslinic acid suppresses about 40 to 60%
  • maslinic acid salt suppresses about 40 to 60%
  • erythrodiol about 50 to 70%
  • about 40 to 60% inhibition in persolic acid about 30 to 50% inhibition in baioruol
  • about 25 to 45% inhibition in berylic acid about 25 to 45% in berylin
  • a high anti-atherosclerotic effect can be enjoyed by containing maslinic acid, erythrodiol, persolic acid, evanol, veric acid, perrin, their physiologically acceptable salts and their derivatives. Things.
  • the present invention is effective in using one or more kinds selected from the group consisting of maslinic acid, erythrodiol, persolic acid, babol, veric acid, verin, their physiologically acceptable salts and their derivatives.
  • the present invention relates to an agent for a vascular disorder contained as a component.
  • 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 sclerosis, abdominal aortic sclerosis, obstructive arteriosclerosis, renal arteriosclerosis, carotid sclerosis, fundus arteriosclerosis, cerebral arteriosclerosis, restenosis after PTCA, myocardial infarction ⁇ Ischemic heart disease such as angina, cerebral infarction ⁇ Cerebrovascular disease such as stroke. That is, the agent for a vascular disorder disease of the present invention has an effect on vascular smooth muscle cells involved in the occurrence of vascular disorders, thereby producing arteriosclerosis due to the development of a cell proliferative vascular lesion mainly composed of vascular smooth muscle cells, and after PTCA.
  • Preventive effects include inhibiting the proliferation and XI // migration of vascular smooth muscle cells to prevent atherosclerotic foci and intimal hyperplasia, and to prevent vascular disease such as atherosclerosis and restenosis after PTCA. Indicates that a disorder is prevented.
  • the therapeutic effect is to suppress the proliferation and Z or migration of vascular smooth muscle cells further, or to reduce the total number of vascular smooth muscle cells by rapidly decreasing the number of vascular smooth muscle cells that have proliferated. Demonstrates the treatment of vascular disorders by suppressing the growth of intimal hyperplasia, preventing the rupture of atherosclerotic lesions, and eliminating intimal hyperplasia.
  • the present invention relates to maslinic acid, erythritol, persolic acid, ebaol, veric acid, veline, physiologically acceptable salts thereof and derivatives thereof, wherein the vascular disease is arteriosclerosis.
  • the present invention relates to an anti-atherosclerosis agent comprising one or more selected from the group consisting of an active ingredient.
  • Arteriosclerosis is a generic term for many diseases in which the arterial wall thickens and loses elasticity, and refers to systemic cardiovascular disorders. Specifically, it refers to coronary atherosclerosis, abdominal aortic sclerosis, renal atherosclerosis, carotid atherosclerosis, fundus atherosclerosis, cerebral atherosclerosis, etc.
  • the present invention relates to an anti-atherosclerosis agent containing the above-mentioned substance as an active ingredient, having an effect on vascular smooth muscle cells involved in the formation of atherosclerotic lesions.
  • an anti-arteriosclerotic agent containing one or more selected from the group consisting of maslinic acid, persolic acid and their physiologically acceptable salts, or derivatives thereof as an active ingredient is useful for vascular smoothing.
  • 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-arterial sclerosis agent, which is very preferable.
  • the present invention relates to maslinic acid, erythrodiol, ursolic acid, ebaol, diphosphoric acid, berylin, a physiologically acceptable salt thereof, and a physiologically acceptable salt thereof, wherein the vascular disorder is restenosis after PTCA.
  • the present invention relates to an anti-restenotic agent after PTCA, containing one or more selected from the group consisting of derivatives as an active ingredient.
  • the anti-restenotic agent of the present invention when administered orally and / or parenterally, exhibits the aforementioned intimal hyperplasia-suppressing effect.
  • the anti-restenotic agent after PTCA of the present invention includes maslinic acid, erythrodiol, ursolic acid, and the like, which have an inhibitory effect on vascular smooth muscle cell proliferation and / or an inhibitory effect on vascular smooth muscle cell migration.
  • the anti-restenotic agent after PTCA of the present invention exhibits an effect of suppressing hypertrophy by ingesting it, thereby improving or preventing ischemic heart disease and greatly contributing to prolonging the survival rate and the like. Is what you do.
  • an anti-restenotic agent containing one or more selected from the group consisting of maslinic acid, persolic acid, a physiologically acceptable salt thereof, or a derivative thereof as an active ingredient is useful for vascular smoothing. Since it has a muscle cell proliferation inhibitory effect and a vascular smooth muscle cell migration inhibitory effect, it can be used as a powerful anti-restenosis agent, and is very preferable.
  • physiologically acceptable salts or glycosides of maslinic acid, erythrodiol, persolic acid, ebaol, veric acid, and bellin are generally water-soluble, and therefore are vascular disorders such as water-based or emulsified. It can be suitably blended by uniformly dissolving or dispersing it in the preparation.
  • beverages and the like are often commercialized in aqueous or lactic acid systems.
  • maslinic acid, erythritol, ursolic acid, ebaol, vegulinic acid, and vegulin may be used as necessary in this case.
  • the salt or rooster trisaccharide that is acceptable for the above can be suitably blended.
  • maslinic acid, erythrodiol, persolic acid, evanol, verinic acid, verinin, their physiologically acceptable salts and their derivatives have a strong effect and can be used in small amounts of vascular disorders.
  • vascular smooth muscle cell proliferation inhibitory effect, vascular smooth muscle cell migration inhibitory effect, etc. which are usually required. Since there is ample room for other components to be combined from the aspect, other functions can be further enhanced, which is preferable.
  • vascular smooth muscle cell proliferation can be achieved.
  • the present invention enables the production of inhibitors, vascular smooth muscle cell migration inhibitors, anti-cell proliferative vascular lesion agents, agents for vascular disorders, and the like.
  • the LD 50 value is at least 200 mg / kg body weight, confirming that the safety is extremely high. This is because maslinic acid, erythrodiol, persolic acid, baioruul, vericulinic acid, veriline, which have vascular smooth muscle cell proliferation inhibitory effect, vascular smooth muscle cell migration inhibitory effect, etc. It shows that the salts and their derivatives can be administered safely.
  • the vascular smooth muscle cell proliferation inhibitor of the present invention comprises directly or indirectly orally and / or parenterally administering the vascular smooth muscle cell, including contacting and / or including the vascular smooth muscle cell. It exhibits a growth inhibitory effect. Furthermore, a more favorable effect can be obtained by continuous intake. As will be described later in detail, these preparations can be administered orally and / or as a pharmaceutical composition to humans and animals together with pharmacologically acceptable bases and the like according to known pharmaceutical manufacturing methods. It is administered parenterally.
  • the term “contact and / or inclusion in vascular smooth muscle cells” means that the substance group of the present invention specifically or non-specifically binds to vascular smooth muscle cells and / or is taken up into the cells. In other words, the various preparations of the present invention exhibit more effects when used in such an embodiment.
  • the amount of two or more types is not specified, and the type of triterpenes, the purpose of use for prevention or treatment, the period of use, the amount used, the age, sex, weight, and whether or not directly ingested , material Depending on the strength of the required effect, it may be determined as appropriate based on whether or not it is blended.
  • 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.
  • % By weight, more preferably 0.01 to 99.99% by weight, still more preferably 0.05 to 99.99% by weight, more preferably 0.5 to 9 to 99.99% by weight, more preferably 0.5 to 5% by weight.
  • the amount may be up to 99.99% by mass, more preferably 1 to 99.99% 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. As will be described in detail later, when used as a raw material, it is preferable that the concentration is relatively high.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the vascular smooth muscle cell growth inhibitor of the present invention, preferably from 0.0001 to 99.99% by mass, It is preferably 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, further preferably 0.01 to 99.99% by mass, and still more preferably 0.1 to 99.99% by mass. And more preferably 1 to 99.99% by mass.
  • the content is preferably 0.0001 to 99.99% by mass, It is preferably 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.99% by mass, and still more preferably 0.1; It is preferably contained in an amount of from 9 to 99.99% by mass, more preferably from 1 to 99.99% by mass.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the vascular smooth muscle cell growth inhibitor of the present invention, preferably 0.0001 to 99.99% by mass, more preferably Is 0.001 to 99.99% by mass, More preferably from 0.005 to 99.99% by mass, more preferably from 0.01 to 99.99% by mass, more preferably from 0.1 to 99.99% by mass, and still more preferably from 1 to 99.99% by mass. %.
  • Baobal and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the vascular smooth muscle cell proliferation inhibitor of the present invention, preferably 0.0001 to 99.99% by mass, more preferably Is 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass, More preferably, it is contained in an amount of 1 to 99, 99% by mass.
  • beryric acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the vascular smooth muscle cell proliferation inhibitor of the present invention, preferably 0.0005 to 99.99% by mass, More preferably, 0.001 to 99.99% by mass, further preferably 0.005 to 99.99% by mass, further preferably 0.01 to 99.99% by mass, and still more preferably 0.1 to 99.99% by mass. %, More preferably 1 to 99.99% by mass.
  • verveline and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient during the inhibition of vascular smooth muscle cell proliferation in the present invention, preferably 0.0005 to 99.99% by mass, Preferably from 0.001 to 99.99 mass%, more preferably from 0.005 to 99.99 mass%, more preferably from 0.01 to 99.99 mass%, more preferably from 0.1 to 99.99 mass%. %, More preferably 1 to 99.99% by mass.
  • the agent for inhibiting vascular smooth muscle cell migration comprises directly or indirectly administering orally or parenterally by contacting and / or including vascular smooth muscle cell to inhibit the vascular smooth muscle cell migration.
  • the effect is exhibited. Furthermore, a more favorable effect can be obtained by continuous intake.
  • vascular smooth muscle cells means that the substance group of the present invention specifically or non-specifically binds to vascular smooth muscle cells and / or is taken up into the cells. Others are as described above.
  • the vascular smooth muscle cell migration inhibitor of the present invention is selected from the group consisting of maslinic acid, ursolic acid and their physiologically acceptable salts, or derivatives thereof.
  • the amount of one or more compounds is not specified, and the type of triterpene, the purpose of use for prophylaxis or treatment, the period of use, the amount, the age, sex, body weight, and direct oral use It may be determined appropriately depending on the strength of the effect required, based on whether it is to be taken or to be blended as a raw material. Although not limited to the following, 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, still 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 9% by mass. 99.99% by mass, more preferably 1 to 99.99% by mass.
  • the higher the content the stronger the effect.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the vascular smooth muscle cell migration inhibitor of the present invention, preferably from 0.0001 to 99.99% by mass, Preferably from 0.001 to 99.99% by mass, more preferably from 0.005 to 99.99% by mass, even more preferably from 0.01 to 99.99% by mass.
  • the content is preferably 99.99% by mass, more preferably 0.1 to 99.99% by mass, and still more preferably 1 to 99.99% by mass.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the vascular smooth muscle cell migration inhibitor of the present invention, it is preferably 0.0001 to 99.99% by mass, more preferably Is 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.99% by mass, and still more preferably 0.1 to 99.99% by mass. More preferably, it is contained in an amount of 1 to 99.99% by mass.
  • the anti-cell proliferative vascular lesion agent of the present invention can be directly or indirectly administered orally and / or parenterally, including by contacting and / or encapsulating vascular smooth muscle cells, to produce an anti-cell proliferative agent. It exerts a proliferative vascular lesion effect. Furthermore, a more favorable effect can be obtained by continuous ingestion. As will be described in detail later, these preparations can be used as pharmaceutical compositions orally and / or parenterally for humans and animals, together with pharmacologically acceptable bases, etc., according to known pharmaceutical manufacturing methods. Administered as described above, and as described above.
  • the anti-cell proliferative vascular lesion agent of the present invention is selected from the group consisting of maslinic acid, erythrodiol, persolic acid, baol, berylic acid, berylin, physiologically acceptable salts thereof and derivatives thereof.
  • the amount of the species or two or more types is not specified, and the type of triterpene, the purpose of prophylaxis or treatment, the period of use, the amount, the age, sex, weight, and direct oral use It may be determined appropriately according to the strength of the required effect, based on whether the substance is to be ingested or formulated as a raw material.
  • the concentration is relatively high.
  • the anti-cell proliferative vascular lesion agent of the present invention contains maslinic acid and a physiologically acceptable salt thereof or a derivative thereof as an active ingredient, preferably 0.0001 to 99.99% by mass, It is preferably 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, further preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass.
  • the content is preferably 99% by mass, more preferably 1 to 99.99% by mass.
  • erythrodiol and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-cell proliferative vascular lesion agent of the present invention, it is preferably 0.0001 to 99.99% by mass, Preferably from 0.001 to 99.99% by mass, more preferably from 0.005 to 99.99% by mass, further preferably from 0.01 to 99.99% by mass, more preferably from 0.1 to 99.99% by mass. And more preferably 1 to 99.99% by mass.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-cell proliferative vascular lesion agent of the present invention, it is preferably 0.0001 to 99.99% by mass, It is preferably 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, further preferably 0.01 to 99.99% by mass, and still more preferably 0.1 to 99.99% by mass. And more preferably 1 to 99.99% by mass.
  • the anti-cell proliferative vascular lesion agent of the present invention contains ⁇ baol and its physiologically acceptable salts or derivatives thereof as an active ingredient, it is preferably 0.00. 001 to 99.99% by mass, more preferably 0.001 to 99.99% by mass, still more preferably 0.005 to 99.99% by mass, further preferably 0.01 to 99.99% by mass, The content is more preferably 0.1 to 99.99% by mass, and even more preferably 1 to 99.99% by mass.
  • beryric acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-cell proliferative vascular lesion agent of the present invention, preferably 0.0005 to 99.99% by mass, More preferably, 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, further preferably 0.01 to 99.99% by mass, still more preferably 0.1 to 99% by mass.
  • the content is preferably 99% by mass, more preferably 1 to 99.99% by mass.
  • the anti-cell proliferative vascular lesion agent of the present invention contains vereline and a physiologically acceptable salt thereof or a derivative thereof as an active ingredient, preferably 0.0005 to 99.99% by mass, More preferably from 0.001 to 99.99% by mass, further preferably from 0.005 to 99.99% by mass, further preferably from 0.01 to 99.99% by mass, still more preferably from 0.1 to 99.99% by mass. %, More preferably 1 to 99.99% by mass.
  • the anti-intimal thickening agent of the present invention has an intimal thickening inhibitory effect by direct or indirect oral and / or parenteral administration, including contact and / or inclusion of vascular smooth muscle cells. Is expressed. Furthermore, a more favorable effect can be obtained by continuous intake. As will be described in detail later, these preparations are orally and / or as a pharmaceutical composition to humans and animals, together with pharmacologically acceptable bases and the like, according to known pharmaceutical manufacturing methods. It is administered parenterally. Others are as described above.
  • 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, still 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% by mass. 99 mass%, more preferably 1 to 99.99 mass%.
  • the higher the content the stronger the effect.
  • a case where the concentration is relatively high is preferable.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-intimal thickening agent of the present invention, preferably 0.0001 to 99.99% by mass, more preferably Is 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.99% by mass, and still more preferably 0.1 to 99.99% by mass. %, More preferably 1 to 99.99% by mass.
  • erythrodiol and its physiologically acceptable salts or derivatives thereof are contained as active ingredients in the anti-intimal thickening agent of the present invention, preferably 0.001 to 99.99% by mass, more preferably Is 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass, More preferably, the content is 1 to 99.99% by mass.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-intimal thickening agent of the present invention, preferably 0.0001 to 99.99% by mass, more preferably 0.
  • the content is 1 to 99.99% by mass.
  • ebaol or a physiologically acceptable salt thereof or a derivative thereof is contained as an active ingredient in the anti-intimal thickening agent of the present invention, preferably 0.0001 to 99.99% by mass, more preferably 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass. %, More preferably 1 to 99.99% by mass.
  • beryric acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-intimal thickening agent of the present invention, preferably 0.0005 to 99.99% by mass, It is preferably 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, more preferably 0.01 to 99.99% by mass, and still more preferably 0.1 to 99.99% by mass.
  • the content is preferably 99% by mass, more preferably 1 to 99.99% by mass.
  • bellin and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-intimal thickening agent of the present invention, preferably 0.0005 to 99.99% by mass, more preferably 0. 001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass, and still more preferably Is preferably 1 to 99.99% by mass.
  • the anti-atherosclerotic agent of the present invention can contact and / or contain vascular smooth muscle cells. And by directly or indirectly administering orally and / or parenterally, the compound exhibits its anti-arterial stiffening effect. Furthermore, a more favorable effect can be obtained by continuous intake.
  • these preparations can be administered orally and / or parenterally as a pharmaceutical composition to humans and animals together with pharmacologically acceptable bases and the like according to known pharmaceutical manufacturing methods. Is administered in a controlled manner. Others are as described above.
  • the amount of the two or more compounds is not specified, and the type of triterpenes, the purpose of use for prevention or treatment, the period of use, the amount, the age, sex, body weight, and whether or not directly ingested It may be appropriately determined according to the required strength of the effect, taking into account whether or not it is blended as a raw material.
  • 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 from 0.01 to 99.99% by mass, still more preferably from 0.05 to 99.99% by mass, more preferably from 0.1 to 99.99% by mass, more preferably from 0.5 to 9% by mass. 99.99% by mass, more preferably 1 to 99.99% by mass.
  • the higher the content the stronger the effect.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-arteriosclerotic agent of the present invention, preferably from 0.0001 to 99.99% by mass, It is preferably 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, and still more preferably 0.01 to 99.99% by mass. %, More preferably 0.1 to 99.99% by mass, and still more preferably 1 to 99.99% by mass.
  • erythrodiol and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-atherosclerotic agent of the present invention, preferably 0.001 to 99.99% by mass, more preferably 0. 001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass, and still more preferably Is preferably 1 to 99.99% by mass.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-atherosclerotic agent of the present invention, it is preferably 0.0001 to 99.99% by mass, more preferably 0.1% by mass. 001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass, and still more preferably Is preferably 1 to 99.99% by mass.
  • ebaol and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-atherosclerotic agent of the present invention, preferably 0.0001 to 99.99% by mass, more preferably 0. 001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass. More preferably, the content is 1 to 99.99% by mass.
  • beryric acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the anti-arteriosclerotic agent of the present invention, preferably 0.0005 to 99.99% by mass, More preferably, 0.001 to 99.99% by mass, still more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.99% by mass, still more preferably 0.1 to 99% by mass. 99% by mass, more preferably 1 to 99. Preferably, it is contained in an amount of 99% by mass.
  • verin and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient in the anti-atherosclerotic agent of the present invention, preferably 0.0005 to 9.9.99% by mass, More preferably from 0.001 to 99.9% by mass, even more preferably from 0.005 to 99.9% by mass, even more preferably from 0.01 to 99.9% by mass, More preferably, the content is 0.1 to 99.99% by mass, more preferably 1 to 99.99% by mass.
  • the agent for a vascular disorder of the present invention is characterized by containing maslinic acid, erythrodiol, persolic acid, baol, beculinic acid, and beperin, and the use thereof is optional. It can be used as a drug for vascular disorders or as a raw material in a wide range of fields such as pharmaceuticals, quasi-drugs, and health foods.
  • the compounding amount of the agent for a vascular disorder of the present invention is not specified because it differs depending on conditions such as the use, administration form, administration target species, age, gender, weight, degree of symptoms, and health condition. Naturally, it is an amount that is effective in preventing and / or treating the occurrence and proliferation of arteriosclerosis by inhibiting the proliferation and migration of vascular smooth muscle cells.
  • the agent for a vascular disorder disease of the present invention has an antivascular disorder disease effect by direct or indirect oral or Z or parenteral administration, including contact and / or inclusion of vascular smooth muscle cells. Is expressed. Furthermore, a more favorable effect can be obtained by continuous intake.
  • these preparations are orally and / or as pharmaceutical compositions for humans and animals together with pharmacologically acceptable bases and the like according to known pharmaceutical preparation methods. Or parenteral administration. Others are as described above.
  • the mixing amount of two or more Not required, necessary based on the type of triterpene, purpose of use for prevention or treatment, duration of use, amount, age, gender, weight, target oral use or combination as raw material, etc. May be determined appropriately according to the strength of the effect.
  • 0.0001% by weight or more preferably from 0.0001 to 99.99% by weight, more preferably 0.001 to 99.99 mass 0/0, more favorable Mashiku 0.005 To 99.99% by mass, more preferably 0.01% to 99.9% by mass, still 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, and more preferably 1 to 99.99% by mass.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the agent for a vascular disorder disease in the present invention, preferably 0.0001 to 99.99% by mass, more preferably 0. 001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.9% by mass, and still more preferably 0.1 to 99.99% by mass. More preferably, the content is 1 to 99.99% by mass.
  • the content is preferably 0.0001 to 99.99% by mass, more preferably Is 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass. %, More preferably 1 to 99.99% by mass.
  • the amount is preferably 0.001 to 99.99% by mass, Preferably from 0.001 to 99.99% by mass, more preferably from 0.005 to 99.99% by mass, even more preferably from 0.01 to 99.99% by mass.
  • the content is preferably 99% by mass, more preferably 0.1 to 99.99% by mass, and still more preferably 1 to 99.99% by mass.
  • ⁇ baol and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the agent for a vascular disorder disease of the present invention, preferably 0.0001 to 99.99% by mass, more preferably 0.1% by mass. 001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, more preferably 0.01 to 99.9% by mass, more preferably 0.1 to 99.99% by mass, More preferably, the content is 1 to 99.99% by mass.
  • beryric acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the agent for a vascular disorder disease in the present invention, preferably 0.0005 to 99.99% by mass, more preferably 0.001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.9% by mass, and still more preferably 0.1 to 99.99% by mass. %, More preferably 1 to 99.99% by mass.
  • vereline and its physiologically acceptable salts or derivatives thereof are contained as an active ingredient in the agent for vascular disorders in the present invention, preferably 0.0005 to 99.99% by mass, more preferably 0. 001 to 99.99% by mass, more preferably 0.005 to 99.99% by mass, still more preferably 0.01 to 99.99% by mass, more preferably 0.1 to 99.99% by mass, and Preferably, the content is 1 to 99.99% by mass.
  • the dosage required to obtain an appropriate anti-atherosclerotic effect by ingesting the derivative of the above-mentioned compound varies depending on the form of ingestion, the sex, weight, and physical condition of the subject, and is not particularly limited.For example, 0.001 g / Days or more, preferably 0.01 g / day or more, particularly preferably 0.01 g / day or more.
  • the anti-atherosclerotic agent of the present invention in which the vascular disorder is arteriosclerosis, is directly or indirectly administered orally and / or parenterally, including contacting and / or including vascular smooth muscle cells. By doing so, the anti-atherosclerosis effect is exhibited. Furthermore, a more favorable effect can be obtained by continuous intake.
  • these preparations can be administered orally and / or parenterally to humans and animals as pharmaceutical compositions together with pharmacologically acceptable bases, etc., according to known pharmaceutical manufacturing methods. Is administered. Others are as described above.
  • the amount of two or more types is not specified, and the type of triterpene, the purpose of prophylaxis or treatment, the period of use, the amount, the age, sex, weight, and direct ingestion It should be determined appropriately according to the required strength of the effect, based on whether the compound should be used as a raw material.
  • 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 0.0005 to 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, more preferably 0.1 to 99.99% by mass, and still more preferably 0.5 to 9% by mass. 99.99% by mass, more preferably 1 to 99.99% by mass.
  • the higher the content the stronger the effect, but 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.
  • the concentration is relatively high.
  • the anti-restenosis agent of the present invention wherein the vascular disorder is restenosis after PTCA, comprises directly or indirectly orally and / or parenterally comprising contacting and / or including vascular smooth muscle cells.
  • vascular disorder is restenosis after PTCA
  • PTCA vascular smooth muscle cells
  • these preparations are orally and / or parenterally administered to humans and animals as pharmaceutical compositions, together with pharmacologically acceptable bases, etc., according to known pharmaceutical manufacturing methods. Is administered. Others are as described above.
  • the anti-restenotic agent of the present invention is selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, vertulinic acid, veline, physiologically acceptable salts thereof and derivatives thereof.
  • the amount of the species or two or more species is not specified, and the type of triterpene, the purpose of use for prevention or treatment, the period of use, the amount, age, sex, body weight, and direct ingestion It may be determined appropriately according to the required strength of the effect, based on whether the compound is to be blended as a raw material.
  • the content may be 0.1 to 99.9% by mass, more preferably 0.5 to 99.9% by mass, and further preferably 1 to 99.9% 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. As will be described in detail later, when used as a raw material, a case where the concentration is relatively high is preferable.
  • maslinic acid and its physiologically acceptable salts or derivatives thereof have an inhibitory effect on vascular smooth muscle cell proliferation, an inhibitory effect on vascular smooth muscle cell migration, and an inhibitory effect on intimal hyperplasia. It is preferable because it has very strong effects such as anti-cell proliferative vascular lesion effects such as anti-atherosclerosis and anti-vascular disease diseases effects such as anti-atherosclerosis and anti-restenosis after PTCA. That is, a vascular smooth muscle cell proliferation inhibitor and / or vascular smooth muscle, comprising as an active ingredient one or more selected from the group consisting of maslinic acid and its physiologically acceptable salts or derivatives thereof.
  • the present invention relates to a cell migration inhibitor, an anti-cell proliferative vascular lesion agent such as anti-intimal thickening and anti-arteriosclerosis, and an agent for vascular disorders such as anti-arteriosclerosis and anti-restenosis after PTCA.
  • an anti-cell proliferative vascular lesion agent such as anti-intimal thickening and anti-arteriosclerosis
  • an agent for vascular disorders such as anti-arteriosclerosis and anti-restenosis after PTCA.
  • maslinic acid can be obtained from plants that have been cultivated relatively regularly called olive plants and have already been crushed as edible oil. Excellent in properties and preferred.
  • the preparation of the present invention containing maslinic acid which has the intended effects, expresses the above-mentioned effects by direct or indirect oral and / or parenteral administration. It is. Furthermore, a more favorable effect can be obtained by continuous intake.
  • maslinic acid and its physiologically acceptable salts or derivatives thereof are also preferred as health foods because some of them are obtained from natural products that have already experienced eating, as described above.
  • these preparations are administered orally and / or as a pharmaceutical composition to humans and animals together with pharmacologically acceptable bases and the like, according to known pharmaceutical manufacturing methods. It is administered parenterally.
  • the amount of maslinic acid and its physiologically acceptable salts or derivatives thereof at that time is not specified without limitation, and the purpose of the use, whether to prevent or treat, the period of use, the amount, and the intended use Based on the age, gender, body weight, whether the product should be taken directly orally, or whether it should be used as a raw material, it can be determined appropriately according to the strength of the required effect. Although it is not limited to the following, for example, 0.0001% by mass or more, preferably 0.0001 to 99.999% by mass, more preferably 0.001 to 9.9.99% by mass. %, More preferably 0.05 to 99.99% by mass, and still more preferably 0.01 to 99.9.99%.
  • % By mass more preferably from 0.05 to 99.9% by mass, further preferably from 0.1 to 99.9% by mass, more preferably from 0.5 to 99.9% by mass, Preferably, it is 1 to 99.9% by mass.
  • the higher the content the stronger the effect, but 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.
  • the concentration is relatively high.
  • the agent for a vascular disorder of the present invention and the like can be safely orally and parenterally administered to humans and animals as pharmaceuticals, quasi-drugs and the like.
  • Parenteral administration includes, for example, intravenous injection, arterial injection, intramuscular injection, subcutaneous injection, intradermal injection, intraperitoneal injection, intraspinal injection, epidural injection, transdermal administration, pulmonary administration, nasal administration, Enteral administration, buccal administration, transmucosal administration, and the like are mentioned.
  • Examples of the dosage form include injections, suppositories (such as rectal suppositories, urethral suppositories, vaginal suppositories), and external preparations (including injections, Rinsing agent, mouthwash, poultice, inhalant, spray, azole, enema, liniment, cleaning agent, disinfectant, nose drops, ear drops, etc.), patch, skin absorption tape, Examples include skin external preparations and ointments (such as pastes, liniments, and lotions).
  • Oral preparations include, for example, tablets for internal use (uncoated tablets, sugar-coated tablets, coated tablets, enteric-coated tablets, chewable tablets, etc.) and buccal tablets (puckal tablets, sublingual tablets, troche tablets, adhesive tablets, etc.) , Powders, capsules (hard capsules, soft capsules, etc.), granules (coated, pills, troches, liquids, or pharmaceutically acceptable sustained-release preparations etc.) No.
  • the liquid preparation for oral administration include a liquid preparation for internal use, a shaking mixture, a suspension, an emulsion, a syrup, a dry syrup, an elixir, an infusion, a decoction, and a limonade. These preparations are administered as pharmaceutical compositions together with pharmacologically acceptable bases, carriers, excipients, disintegrants, lubricants, coloring agents, etc., according to known pharmaceutical manufacturing methods. .
  • Carriers and excipients used in these preparations include, for example, lactose, pudose, sucrose, Examples include mannitol, potato starch, corn starch, calcium carbonate, calcium phosphate, calcium sulfate, crystalline cellulose, kanzo powder, gentian powder and the like.
  • binder used in these preparations examples include starch, tragacanth gum, gelatin, syrup, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, hydroxypropylcellulose, methylcellulose, ethylcellulose and carboxymethylcellulose.
  • Disintegrants used in these preparations include, for example, starch, agar, gelatin powder, potassium carboxymethylcellulose sodium, calcium carboxymethylcellulose, crystalline cellulose, calcium carbonate, sodium hydrogencarbonate, sodium alginate and the like.
  • Lubricants used in these preparations include, for example, magnesium stearate, talc, hydrogenated vegetable oil, macrogol and the like.
  • coloring agents used in these preparations those permitted to be added to pharmaceuticals can be used.
  • a pH adjuster When preparing injections, if necessary, a pH adjuster, a buffer, a stabilizer, a solubilizer, and the like are added, and each injection is prepared by a conventional method.
  • the film may be coated with pyrrolidone, cellulose acetate fluorate, hydroxypropyl methylcellulose phthalate, methyl methacrylate, methacrylic acid polymer or the like, or may be coated with two or more layers.
  • capsules made of a substance such as ethyl cellulose or gelatin may be used.
  • the form of the external preparation may be transdermal administration or transmucosal administration such as intraoral or nasal.
  • Solid, semi-solid, semi-solid, or liquid formulations for administration may be transdermal administration or transmucosal administration such as intraoral or nasal.
  • liquid preparation examples include pharmaceutically acceptable emulsions such as emulsions and lotions, tinctures for external use, and liquid preparations for transmucosal administration.
  • the formulation contains commonly used diluents, for example, ethanol, oils, emulsifiers and the like.
  • semisolid preparations include ointments such as oily ointments and hydrophilic ointments.
  • This preparation contains, as a commonly used base or carrier, for example, water, petrolatum, polyethylene glycol, oil, surfactant and the like.
  • Semi-solid or solid preparations include, for example, patches for transdermal or transmucosal (intraoral, nasal) administration such as plasters (rubber plasters, plaques, etc.), films, tapes, or cataplasms Agents and the like.
  • This preparation can be used as a commonly used base or carrier, for example, rubber-based polymers such as natural rubber, butadiene rubber, synthetic rubber such as SBR and SIS, mud-forming agents such as gelatin, kaolin and zinc oxide, and carbohydrates.
  • rubber-based polymers such as natural rubber, butadiene rubber, synthetic rubber such as SBR and SIS
  • mud-forming agents such as gelatin, kaolin and zinc oxide
  • carbohydrates for example, rubber-based polymers such as natural rubber, butadiene rubber, synthetic rubber such as SBR and SIS, mud-forming agents such as gelatin, kaolin and zinc oxide, and carbohydrates.
  • hydrophilic polymers such as xymethylcellulose sodium and sodium polyacrylate, tackifiers such as
  • compositions may further use adjuvants such as stabilizers, solubilizers, transdermal absorption enhancers, or additives such as fragrances and preservatives.
  • adjuvants such as stabilizers, solubilizers, transdermal absorption enhancers, or additives such as fragrances and preservatives.
  • the present invention relates to one or two members selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin, physiologically acceptable salts thereof and derivatives thereof.
  • the present invention relates to a vascular smooth muscle cell growth inhibitor raw material containing at least one species.
  • one or more sources selected from the group consisting of maslinic acid, erythrodiol, persolic acid, baol, beculinic acid, beperin, their physiologically acceptable salts and their derivatives,
  • those obtained from natural raw materials and those obtained artificially can be suitably used, but those obtained from natural raw materials have the merit of security.
  • Its purpose is to suppress vascular smooth muscle cell proliferation. Since it is an antidote, it is preferable that its purity is higher.
  • the advantage of high purity is that the anti-atherosclerosis effect and the like can be greatly improved, and that impurities are removed. That is, it greatly contributes to the improvement of product quality, such as avoiding the danger of unpredictable side effects due to impurities, etc., avoiding unpredictable troubles when manufacturing vascular smooth muscle cell proliferation inhibitors, and improving handling. Therefore, those with higher purity are more preferable, especially those obtained from natural raw materials, and those isolated are more preferable.
  • maslinic acid, erythrodiol, ursolic acid, ebaol, veline modification, veline, their physiologically acceptable salts and their salts in the present invention One or more selected from the group consisting of derivatives can be obtained as a substantially white or colorless solid, semi-solid, liquid, etc., which is suitable without adding an extra color to the vascular smooth muscle cell growth inhibitor. It is preferable because it has the merit that it can be blended into a mixture.
  • the purity of one or more kinds selected from the above is preferably higher as the purity is higher.
  • the strength is not generally defined, but the type of triterpene, the purpose of prevention or treatment, the dosage form, and the manufacturing method It may be determined as appropriate based on the manufacturing cost.
  • 0.1% by mass or more preferably 0.1 to 99.9% by mass, more preferably 1 to 99.99% by mass, and still more preferably 10 to 9% by mass.
  • the anti-arteriosclerotic effect and the like can be suitably obtained for producing a vascular smooth muscle cell proliferation inhibitor or when combined with a drug, a quasi-drug, an external preparation for the skin, a health food, or the like. It is preferable because it can be exerted.
  • the present invention relates to a vascular smooth muscle cell migration inhibitor raw material containing one or more selected from the group consisting of maslinic acid, persolic acid, and physiologically acceptable salts thereof, and derivatives thereof.
  • the origin of one or more selected from the group consisting of maslinic acid, ursolic acid and their physiologically acceptable salts, or derivatives thereof there is no particular limitation. Both obtained and artificially obtained ones can be suitably used, but those obtained from natural raw materials have the advantage of a sense of security. Further, as the purpose is an agent for inhibiting vascular smooth muscle cell migration, it is preferable that the purity thereof is higher. The advantage of high purity is that the anti-arteriosclerosis effect and the like can be greatly improved, and that impurities are removed.
  • vascular smooth muscle cell migration inhibitor greatly contributes to the improvement of product quality, such as avoiding the danger of unpredictable side effects due to impurities, etc., avoiding unpredictable troubles when manufacturing vascular smooth muscle cell migration inhibitor, and improving handling. Therefore, those with higher purity are more preferable, especially those obtained from natural raw materials, and those isolated are more preferable. Further, when the purity is increased by the isolation and purification treatment, one kind selected from the group consisting of maslinic acid, ursolic acid and physiologically acceptable salts thereof, or derivatives thereof in the present invention. Alternatively, two or more of them can be obtained as a substantially white or colorless solid, semi-solid, liquid, etc., so that the vascular smooth muscle cell migration inhibitor can be suitably blended without adding an extra color. Advantageous and preferred.
  • the purity of one or more selected from the group consisting of maslinic acid, persolic acid and their physiologically acceptable salts, or their derivatives, in the vascular smooth muscle cell migration inhibitor raw material and the like of the present invention is as follows: As described above, the higher the purity, the better. However, it is not specified, and may be determined as appropriate based on the type of triterpenes, the purpose of use for prevention or treatment, the dosage form, the production method, the production cost, and the like. Although not limited to the following, for example, 0.1 mass% or more, preferably 0.1 to 99.9 mass%, more preferably 1 to 99.9 mass%.
  • the anti-arterial hardening effect and the like can be suitably produced for the production of a vascular smooth muscle cell migration inhibitor, or even when it is added to a drug, a quasi-drug, an external preparation for the skin, a health food, or the like. Is preferable because it can exhibit
  • the present invention contains one or more selected from the group consisting of maslinic acid, erythrodiol, persolic acid, baol, veric acid, verin, physiologically acceptable salts thereof and derivatives thereof.
  • Anti-cell proliferative vascular lesion drug material In this case, one or more origins selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, benulinic acid, benline, physiologically acceptable salts thereof and their derivatives
  • any of those obtained from natural raw materials and those obtained artificially can be suitably used, but those obtained from natural raw materials have the merit of security.
  • the higher its purity the better.
  • the advantage of high purity is that the anti-atherosclerosis effect and the like can be greatly improved, and that impurities are removed. In other words, it greatly contributes to the improvement of product quality, such as avoiding the danger of unpredictable side effects due to impurities and the like, avoiding unpredictable troubles when manufacturing anti-cell proliferative vascular lesion agents, and improving handling. Therefore, those with higher purity are more preferable, especially those obtained from natural raw materials, and those isolated are more preferable.
  • the maslinic acid, erythrodiol, urturic acid, ebaol, berylic acid, beryulin, their physiologically acceptable salts and their derivatives in the present invention may be used.
  • the purity of the selected one or more species is preferably higher as described above, but it is not necessarily specified, and the type of triterpene, purpose of prevention or treatment, administration form, It may be determined as appropriate based on the manufacturing method and manufacturing cost.
  • 0.1% by mass or more preferably 0.1 to 9.9.9% by mass, more preferably 1 to 99.99% by mass, and still more preferably 10 to 99% by mass.
  • the anti-arteriosclerotic effect can be suitably exerted for the manufacture of an anti-cell proliferative vascular lesion agent, or even when formulated into a drug, quasi-drug, topical skin preparation, health food, etc. It is preferable because it can be performed.
  • the present invention relates to maslinic acid, erythrodiol, ursolic acid, ebaol, beculinic acid, beperin, their physiologically acceptable salts, and their salts, wherein the cell proliferative vascular lesion is intimal hyperplasia.
  • the present invention relates to a raw material for an anti-intimal thickener comprising one or more selected from the group consisting of derivatives.
  • one or more sources selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, veline, physiologically acceptable salts thereof and derivatives thereof
  • maslinic acid erythrodiol
  • ursolic acid ursolic acid
  • ebaol veric acid
  • veline veline
  • physiologically acceptable salts thereof and derivatives thereof there is no particular limitation, and both those obtained from natural raw materials and those obtained artificially can be suitably used, but those obtained from natural raw materials have the merit of security.
  • an anti-intimal thickening agent the higher its purity, the better.
  • the advantage of high purity is that, in addition to being able to remarkably improve the effect of suppressing internal hypertrophy, impurities are removed, and the like.
  • impurities It can greatly contribute to the improvement of product quality, such as avoiding the danger of unpredictable side effects and the like caused by such factors, avoiding unpredictable troubles during the production of anti-intimal thickeners, and improving handling.
  • the one obtained from a natural raw material is preferable, and the isolated one is more preferable.
  • the purity is increased by the isolation and purification treatment, it comprises the maslinic acid, erythrodiol, persolic acid, ebaol, berylic acid, beperin, physiologically acceptable salts thereof and derivatives thereof in the present invention.
  • One or more selected from the group can be obtained as almost white or colorless solids, semi-solids, liquids, etc., so they should be blended appropriately without adding extra color to the anti-intimal thickener. It is advantageous because it has the advantage that it can be produced.
  • a group consisting of maslinic acid, erythrodiol, ursolic acid, vaoyl, berylic acid, berylin, their physiologically acceptable salts and their derivatives in the anti-intimal thickener raw material and the like of the present invention.
  • the purity of one or more kinds selected from the above is preferably higher as the purity is higher, but is not necessarily defined, and the type of the triterpene, the purpose of prevention or treatment, the administration form, the production method, It may be determined as appropriate based on the manufacturing cost.
  • 0.1% by mass or more preferably 0.1 to 99.9% by mass, more preferably 1 to 99.99% by mass, and further preferably 10 to 9% by mass. 9.99% by mass, more preferably 30 to 99.99% by mass, more preferably 50 to 99.99% by mass, and still more preferably 70 to 99.99% by mass. %, More preferably 90 to 99.99% by mass.
  • the anti-intimal thickening agent can be suitably exerted to produce an anti-intimal thickening agent, or even when formulated into pharmaceuticals, quasi-drugs, skin external preparations, health foods, etc. It is preferable because it can be performed.
  • the present invention relates to one or two members selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, benzoyl, berylic acid, berylin, physiologically acceptable salts thereof, and derivatives thereof.
  • the present invention relates to an anti-atherosclerotic raw material containing at least one kind. This In this case, one or more selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, evanyl, berylic acid, berylin, their physiologically acceptable salts and their derivatives
  • any of those obtained from natural raw materials and those obtained artificially can be suitably used, but those obtained from natural raw materials have the merit of security.
  • the purity thereof is higher.
  • the advantage of high purity is that, in addition to being able to greatly improve the anti-atherosclerotic effect and the like, the fact that impurities are removed is given. In other words, it can greatly contribute to the improvement of product quality, such as avoiding the danger of unpredictable side effects due to impurities and the like, avoiding unpredictable troubles during the production of anti-atherosclerotic agents, and improving handling. For this reason, those having higher purity are more preferable, particularly those obtained from natural raw materials, and those isolated are more preferable.
  • maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, perrin, their physiologically acceptable salts and their salts in the present invention One or more selected from the group consisting of the derivatives of the above can be obtained as a substantially white or colorless solid, semi-solid, liquid, etc., without adding an extra color to the anti-arteriosclerotic agent. It is advantageous because it has a merit that the roosters can be combined properly.
  • the purity of one or more selected is preferably as high as possible as described above, but it is not necessarily defined, and the type of triterpene, the purpose of prevention or treatment, the dosage form, the production method, and the production It may be determined as appropriate based on costs and other factors.
  • 0.1% by mass or more preferably 0.1 to 99.9% by mass, more preferably 1 to 99.9% by mass, and still more preferably 10 to 99% by mass.
  • an anti-atherosclerotic effect can be suitably exerted for producing an anti-atherosclerotic agent, or even when blended in a pharmaceutical, quasi-drug, topical skin preparation, healthy food, etc. It is preferable because you can do it.
  • the present invention relates to at least one or more members selected from the group consisting of maslinic acid, erythrodiol, persolic acid, benzoyl, berylic acid, berylin, physiologically acceptable salts thereof, and derivatives thereof.
  • the present invention relates to a raw material for an agent for vascular disorders containing
  • a raw material for an agent for vascular disorders containing
  • maslinic acid erythrodiol
  • ursolic acid ursolic acid
  • evanyl berylic acid
  • berylin physiologically acceptable salts thereof and their derivatives
  • physiologically acceptable salts thereof and their derivatives There are no particular restrictions on the origin of the two or more species, and any of those obtained from natural raw materials and those obtained artificially can be suitably used, but those obtained from natural raw materials have the merit of a sense of security.
  • the purpose is an agent for a vascular disorder, the higher the purity, the better.
  • the advantages of high purity include not only that the anti-atherosclerotic effect and the like can be greatly improved, but also that impurities are removed. In other words, it greatly contributes to the improvement of product quality, such as avoiding the danger of unpredictable side effects due to impurities, etc., avoiding unpredictable troubles during the manufacture of drugs for vascular disorders, and improving handling. Therefore, those with higher purity are more preferable, particularly those obtained from natural raw materials are preferable, and those isolated are more preferable.
  • the maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, beryulin, physiologically acceptable salts thereof, and their salts in the present invention One or more selected from the group consisting of derivatives can be obtained as almost white or colorless solids, semi-solids, liquids, etc., so that the agent for vascular diseases is not colored. There are advantages such as being able to be suitably blended, preferable.
  • maslinic acid erythrodiol, persolic acid, evaol, berylic acid, beperin, their physiologically acceptable salts and their derivatives in the raw materials for the agent for vascular disorders of the present invention.
  • the purity of one or more species is preferably as high as possible as described above, but is not necessarily specified, and the type of triterpenes, the purpose of prevention or treatment, the dosage form, the production method, and the production It may be determined as appropriate based on cost and other factors.
  • 0.1% by mass or more preferably 0.1 to 99.99% by mass, more preferably 1 to 99.99% by mass, still more preferably 10 to 99.99% by mass, More preferably, it is 30 to 99.99% by mass, more preferably 50 to 99.99% by mass, further preferably 70 to 99.99% by mass, more preferably 90 to 99.99% by mass.
  • it is suitable for the production of an agent for vascular disorders, or for use in pharmaceuticals, quasi-drugs, topical skin preparations, health foods, etc.! ⁇ ⁇ ⁇ ⁇ It is preferable because it can exhibit a curing effect and the like.
  • maslinic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the raw material for a vascular disorder disease in the present invention, preferably 0.1 to 99.99% by mass, more preferably Is from 1 to 99.99% by mass, more preferably from 10 to 99.99% by mass, still more preferably from 30 to 99.99% by mass, more preferably from 50 to 99.99% by mass, and still more preferably from 70 to 99.99% by mass. It is preferably contained in an amount of 99% by mass, more preferably 90 to 99.99% by mass.
  • the content is preferably 0.1 to 99.99% by mass, more preferably ! To 99.99% by mass, more preferably 10 to 99.99% by mass, more preferably 30 to 99.99% by mass, more preferably 50 to 99.99% by mass, and still more preferably 70 to 99.99% by mass. %, More preferably 90 to 99.99% by mass.
  • persolic acid and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the raw material for a vascular disorder disease in the present invention, preferably 0.1 to 99.99% by mass, more preferably 1 to 99.99% by mass, more preferably 10 to 99.99% by mass, more preferably 30 to 99.99% by mass, more preferably 50 to 99.99% by mass, and still more preferably 70 to 99.99% by mass.
  • the content is preferably 99% by mass, more preferably 90 to 99.99% by mass.
  • baobal and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the raw material for an agent for a vascular disorder in the present invention, preferably 0.1 to 99.99% by mass, more preferably 1 to 99.99% by mass, more preferably 10 to 99.99% by mass, more preferably 30 to 99.99% by mass, more preferably 50 to 99.99% by mass, and still more preferably 70 to 99.99% by mass. It is preferred to contain 99% by mass, more preferably 90-99.99% by mass.
  • the raw material for an agent for a vascular disorder according to the present invention contains benulinic acid and a physiologically acceptable salt thereof or a derivative thereof as an active ingredient, preferably 0.1 to 99.99% by mass, It is preferably 1 to 99.99% by mass, more preferably 10 to 99.99% by mass, further preferably 30 to 99.99% by mass, more preferably 50 to 99.99% by mass, and still more preferably 70 to 99.99% by mass.
  • the content is preferably 99.99% by mass, more preferably 90 to 99.99% by mass.
  • vereline and a physiologically acceptable salt thereof or a derivative thereof are contained as an active ingredient in the raw material for a vascular disorder disease in the present invention, preferably 0.1 to 99.99% by mass, more preferably Is from 1 to 99.99% by mass, more preferably from 10 to 99.99% by mass, further preferably from 30 to 99.99% by mass, more preferably from 50 to 99.99% by mass, and still more preferably from 70 to 99% by mass.
  • the content is preferably 99% by mass, more preferably 90 to 99.99% by mass.
  • the present invention provides a method for treating vascular disease, wherein the disease is arteriosclerosis, maslinic acid, erythrodiol,
  • the present invention relates to a raw material for an anti-atherosclerosis agent, which comprises one or more selected from the group consisting of persolic acid, evapor, berylic acid, berylin, a physiologically acceptable salt thereof, and a derivative thereof.
  • one or more origins selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, velulinic acid, velulin, their physiologically acceptable salts and their derivatives
  • maslinic acid erythrodiol
  • ursolic acid ursolic acid
  • ebaol velulinic acid
  • velulin their physiologically acceptable salts and their derivatives
  • the purpose is an anti-atherosclerotic agent, the one with higher purity is more preferable.
  • Advantages of high purity include not only that the anti-atherosclerosis effect can be greatly improved, but also that impurities are removed.
  • the maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, beryulin, physiologically acceptable salts thereof and derivatives thereof in the present invention One or more selected from the group consisting of: can be obtained as an almost white or colorless solid, semi-solid, liquid, etc.
  • the purity of one or more selected is preferably as high as possible as described above, but it is not generally defined, and the type of triterpenes, the purpose of prevention or treatment, the administration form, the production method, It may be determined as appropriate based on the manufacturing cost. Not limited to: For example, 0.1% by mass or more, preferably 0.1 to 99.9% by mass, more preferably 1 to 99.99% by mass, and still more preferably 10 to 99.99% by mass.
  • the anti-arteriosclerotic effect can be suitably exerted for producing an agent for a vascular disorder, or even when blended in a drug, a quasi-drug, an external preparation for the skin, a health food, etc. It is preferable because it can be performed.
  • the present invention comprises one or more selected from the group consisting of maslinic acid, erythrodiol, persolic acid, baol, veric acid, veline, physiologically acceptable salts thereof, and derivatives thereof.
  • maslinic acid erythrodiol
  • persolic acid baol
  • veric acid veline
  • physiologically acceptable salts thereof and derivatives thereof.
  • origins selected from the group consisting of maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, berylin, physiologically acceptable salts thereof and their derivatives
  • berylin physiologically acceptable salts thereof and their derivatives
  • the one with higher purity is more preferable.
  • the advantage of high purity is that the effect of suppressing intimal hyperplasia can be greatly improved, and that impurities are removed. In other words, it greatly improves the quality of products, such as avoiding the danger of unpredictable side effects due to impurities and the like, avoiding unpredictable troubles when manufacturing anti-restenotic agents after PTCA, and improving handling. Since it can contribute, it is preferable that the purity is higher, particularly when it is obtained from a natural material, and more preferably, it is isolated.
  • the purity when the purity is increased by the isolation and purification treatment, it comprises the maslinic acid, erythrodiol, persolic acid, ebaol, berylic acid, beperin, physiologically acceptable salts thereof and derivatives thereof in the present invention.
  • the purity of one or more selected from the above is preferably as high as possible as described above, but is not necessarily defined, and the type of triterpene, purpose of use such as prevention or treatment, dosage form, It may be determined as appropriate based on the manufacturing method and manufacturing cost.
  • 0.1% by mass or more preferably 0.1 to 99.9% by mass, more preferably 1 to 99.9% by mass, and still more preferably 10% to 9% by mass.
  • the effect of suppressing intimal hyperplasia can be suitably used for producing an anti-restenotic agent after PTCA, or even when compounded in pharmaceuticals, quasi-drugs, topical skin preparations, healthy foods, etc. It is preferable because it is possible to exhibit the same.
  • the various raw materials described above include, for example, those obtained by combining the various preparations described above in advance.
  • maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, verulin, their physiologically acceptable salts and their derivatives can be synthesized or extracted from natural products. . Naturally, it can be obtained by extracting it from the plant described above, more specifically, by subjecting it to an extraction treatment with water and / or an organic solvent, followed by a concentration treatment and / or a fractionation purification treatment.
  • each plant can be extracted with water and / or an organic solvent, and the extracted material can be extracted with a solvent, a method utilizing the difference in solubility with impurities, a fractional precipitation method, Separation and purification can be carried out by using a crystallization method, an ion exchange resin method, a liquid chromatography method, or the like alone or in an appropriate combination, or by repeatedly using them.
  • maslinic acid and a physiologically acceptable salt thereof, or a derivative thereof can be naturally obtained by extracting from the above-mentioned plant body.
  • Physiologically acceptable salts can be extracted with water and / or organic solvents from plants such as olive plants, and the extract is further subjected to a solvent extraction method, a method utilizing the solubility difference with impurities, a fractional precipitation method, Separation and purification can be performed by using a recrystallization method, an ion exchange resin method, a liquid chromatography method, or the like, alone or in an appropriate combination, or by repeatedly using the same.
  • the maslinic acid and / or a physiologically acceptable salt thereof contained in the agent for a vascular disorder of the present invention can be obtained mainly from fruits or seeds of a natural plant such as an orifice plant. It can be obtained from its seed coat, leaves, stems and buds. In addition, it can be suitably obtained from these dried, crushed, and B-fatable substances. Of these, defatted fruits (including pericarp) and dried and ground pericarp are preferred.
  • products generated during the production of olive oil such as pressed residue, extracted residue, squeezed residue, pressed oil, extracted oil, degummed soap, deoxidized soap, dark oil, waste decolorizer, deodorant It can be obtained from scum, oiled juices, wastewater and waste filter media. Of these, the oil residue is preferred.
  • defatted olive plants contain high concentrations of maslinic acid and / or its physiologically acceptable salts, and the resulting maslinic acid and / or its This is preferable because it is not necessary to remove the oil component from a physically acceptable 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 olive plant or the defatted product may be converted to a hydrocarbon such as pentathhexane and heptane, a lower fatty acid alkyl ester such as ethyl acetate, and a known water-insoluble organic solvent such as getyl ether.
  • a defatted material obtained by extraction and removal with one or more kinds and further repeating this washing treatment as necessary can also be suitably used.
  • maslinic acid and / or a physiologically acceptable salt thereof contained in the agent for a vascular disorder of the present invention can be obtained. .
  • the organic solvent used to obtain maslinic acid and / or a physiologically acceptable salt thereof from an olive plant may be any of a hydrophilic organic solvent and a hydrophobic organic solvent.
  • hydrophilic organic solvents include methyl alcohol, ethyl alcohol, glycerin, propylene glycol, alcohols such as 1,3-butylene glycol, acetone, tetrahydrofuran, acetonitrile, 1,4-dioxane, pyridine, Known organic solvents such as dimethylsulfoxide, N, N-dimethylformamide, acetic acid, and the like.
  • hydrophobic organic solvent hexane, cyclohexane, carbon tetrachloride, chloroform, dichloromethane, 1
  • organic solvents such as 1,2-dichloroethane, methyl 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.
  • alcohols such as methyl alcohol, ethyl alcohol, glycerin, propylene glycol, 1,3-butylene glycol, acetone, and tetrahydrofuran Organic solvents such as orchid and acetonitrile and hydrated solvents thereof are exemplified.
  • 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 ° €;
  • the extraction efficiency tends to be higher when the temperature is higher, and the extraction can be performed favorably 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, etc.
  • the extraction time depends on other extraction conditions, but is from several minutes to several hours. Although sufficient extraction is performed, it may be determined as appropriate according to 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 water-containing alcohol having a lower alcohol content of 10% by mass to 95% by mass, and most preferably a water-containing lower alcohol having a lower alcohol content adjusted to 30% by mass to 95% by mass. Is preferred.
  • alcohols used in the present invention include methyl alcohol, ethyl alcohol, primary alcohols such as 1-propanol and 1-butanol, and secondary alcohols such as 2-propanol and 2-butanol.
  • solvents such as tertiary alcohols such as —methyl-1-propanol, and liquid polyhydric alcohols such as ethylene glycol, propylene glycol, and 1,3-butylene glycol; Alternatively, two or more kinds can be used in combination.
  • 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 ester and tocophere, and it is not necessary to remove and purify these components.
  • defatted matter is a very effective method of utilizing olive oil, because it can use pressed and extracted cakes obtained by pressing olive oil since it contains residues after oiling. It is an excellent method from the viewpoint of production cost because it uses the materials used in the production.
  • maslinic acid and / or a physiologically acceptable salt thereof extracted from an olive plant maslinic acid and / or / and / or It is preferable to subject the physiologically acceptable salt to a concentration treatment or the like.
  • concentration conditions are not particularly limited, and examples thereof include a method using solubility in water.
  • Maslinic acid and / or its physiologically acceptable salt contained in the agent for a vascular disorder of the present invention is a compound having relatively low polarity and poor water solubility.
  • the crude extract from olive plants is divided into components that are hardly soluble in water and / or components that do not dissolve in water, that is, components that are poorly water-soluble and those that are easily soluble in water. By doing so, it can be significantly concentrated.
  • the components, such as poor water solubility, contained in the crude extract from Olive plant are significantly superior in anti-atherosclerotic effect even compared to the whole crude extract from Olive plant, and maslinic acid and / or its physiology It can be confirmed that the permissible salts are concentrated.
  • Components having poor water solubility can be easily obtained by adding a crude extract from an olive plant to water, stirring and collecting a precipitated portion by filtration or the like.
  • maslinic acid and / or a physiologically acceptable salt thereof contained in the agent for a vascular disorder of the present invention can be concentrated, if necessary, by liquid-liquid distribution using a combination of common solvents. it can.
  • Solvent combinations are generally difficult to define, but examples include water-hydrophobic organic solvent combinations.
  • hydrophobic organic solvents include hexane, carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloromethane.
  • Known organic solvents such as mouth ethane, 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 a physiologically acceptable salt thereof are poorly water-soluble, unnecessary water-soluble components can be removed by separating the water-soluble organic solvent phase. By removing the solvent, maslinic acid and Z or a physiologically acceptable salt thereof can be easily concentrated.
  • maslinic acid and / or a physiologically acceptable salt thereof contained in the agent for a vascular disorder of the present invention can be fractionated from the above-mentioned extract and / or concentrate. It is preferable to carry out a production process. As a result, the concentration can be more than the above concentration, and the target component can be isolated.
  • the advantages of the fractionation / purification treatment include not only that the anti-atherosclerosis effect and the like can be greatly improved, but also that impurities can be removed. That is, when the fractionation and purification are performed, maslinic acid and / or a physiologically acceptable salt thereof can be obtained as white crystals, so that the agent for vascular disorders can be suitably mixed without adding an extra color. It is advantageous because it has the advantages of being able to do so.
  • 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 mouth chromatography among the chromatographies can be carried out without decomposing the maslinic acid and / or its physiologically acceptable salt contained in the agent for vascular disorders of the present invention. It is preferable because fractionation and purification can be performed efficiently.
  • Specific examples of liquid chromatography include normal-phase liquid chromatography, reverse-phase liquid chromatography, thin-layer chromatography, paper chromatography, and high-performance liquid chromatography (HPLC). Any method can be used for fractionating, purifying and treating maslinic acid and / or its physiologically acceptable salt contained in the agent for diseases.
  • normal phase liquid chromatography, reverse phase liquid chromatography, and high performance liquid chromatography (HPLC) are preferable in consideration of the separation ability, the throughput, the number of steps, and the like.
  • normal phase liquid chromatography refers to, for example, the following method. That is, for example, a column was prepared using silica gel as a stationary phase, a hexane-ethyl acetate mixed solution, a black-mouthed formanol mixed solution or the like as a mobile phase, and a crude extract from an olive plant or a concentrate thereof was treated with a load factor of 0. Provide 1 to 5% (wt (mass) / v (volume)) by continuous elution using a single mobile phase or stepwise dissolution by gradually increasing the solvent polarity. This is a method in which a predetermined fraction is eluted by the above method.
  • Reverse phase liquid chromatography refers to, for example, the following method. That is, for example, a column was prepared using silica (ODS) to which octane decylsilane was bonded as a stationary phase, a water-medium mixture, a water-acetonitrile mixture, a water-acetone mixture, and the like, as a mobile phase. From the crude extract or its concentrate at a load factor of 0 ::!
  • HPLC high performance liquid chromatography
  • maslinic acid and / or its physiologically acceptable salt can be very concentrated and can be obtained in a state where impurities have been removed.
  • the purity of maslinic acid and / or its physiologically acceptable salt can be adjusted, and the strength of the 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 / purification treatment, and different fractionation / purification treatments can be combined.
  • fractionation and purification may be performed after concentration, and fractionation and purification may be performed after fractionation and purification, and fractionation and purification may be performed after concentration and then further concentrated. It can also be processed.
  • combinations other than the above-mentioned combinations may be used.
  • a salt can be suitably obtained.
  • the combination is not particularly limited, but a specific example of the series of processing includes the following method.
  • a part or all of the hydrophilic organic solvent is removed from the obtained extract, and if necessary, water is added and stirred, It concentrates by collecting the water-insoluble content which precipitated in the aqueous layer part. Precipitated water-insoluble components can be recovered by filtration, centrifugation or the like.To improve the recovery efficiency, the aqueous solution can be subjected to treatment such as addition of water and stirring if necessary. .
  • the extract in the dried state from which the water and / or hydrophilic organic solvent of the extract obtained from the olive plant has been removed is subjected to the treatment such as addition of water and stirring in the same manner as described above, and the filtration is performed.
  • 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, it is superior in safety to concentration using a solvent, and the range of equipment that can be used is wide. Also, since it contains almost no oil, it is also excellent in the efficiency of concentration-purification, which is preferable. Fractionation and purification of these concentrates by normal-phase and / or reverse-phase chromatography and / or recrystallization results in highly purified maslinic acid and / or its physiologically acceptable properties A salt can be suitably obtained.
  • 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.
  • Concentration treatment can be performed by liquid-liquid distribution with a neutral organic solvent.
  • the extract in the dry state can be concentrated by liquid-liquid partitioning with water-hydrophobic organic solvent by adding water and further adding a hydrophobic organic solvent in the same manner as described above. it can.
  • By fractionating and purifying these concentrates by normal phase 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 particularly high if an amount that can be distributed is used.
  • the amount is preferably 1 to 100 times, more preferably 5 to 50 times, and still more preferably about 10 to 30 times the amount of the dried extract.
  • maslinic acid in a mixture of maslinic acid obtained from olive plant and / or a product obtained in the process of producing olive oil and a physiologically acceptable salt thereof and a physiologically acceptable maslinic acid and a salt thereof is preferably 95% or more, more preferably 95% to 99.99%. The content can be measured by, for example, gas chromatography.
  • the agent for a vascular disorder according to the present invention can be used as a drug for vascular disorders according to the present invention, which can contain maslinic acid and / or a physiologically acceptable salt thereof. An agent 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, so that it can be suitably blended with an agent for vascular disorders. . In addition, other 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 agent for vascular disorders of the present invention provides a more favorable anti-atherosclerotic effect and the like. Is preferred.
  • maslinic acid and / or its physiologically acceptable salts are extracted from olive plants, oleanolic acid and / or its physiologically acceptable salts are simultaneously extracted. Or a physiologically acceptable salt thereof is excellent in compatibility with maslinic acid. Can be directly added to the agent for vascular disorders. This is preferable since a synergistic effect can be expected with respect to the physiological effects 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 and separating and purifying maslinic acid and / or its physiologically acceptable salts from olive plants, by adjusting the conditions, oleic acid and / or its physiologically acceptable salts can be obtained. Of maslinic acid and / or a physiologically acceptable salt thereof, or oleanolic acid and / or a physiologically acceptable salt thereof, separately from the olive plant, and then mixed. You can also get it. 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 effectively employs one or more selected from the group consisting of maslinic acid, erythrodiol, persolic acid, baol, veric acid, verin, their physiologically acceptable salts and their derivatives.
  • the present invention relates to an agent for a vascular disorder contained as a component.
  • maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, verulin, their physiologically acceptable salts and their derivatives have a vascular smooth muscle cell growth inhibitory effect and / or vascular smooth muscle cell It has excellent anti-proliferative vascular lesion effects such as anti-migration effects, intimal hyperplasia suppression and anti-atherosclerosis, and anti-vascular disease effects such as anti-atherosclerosis and anti-restenosis after PTCA.
  • maslinic acid, erythrodiol, ursolic acid, ebaol, berylic acid, berylin, their physiologically acceptable salts and their derivatives are those obtained from natural plants, artificial In particular, when various raw materials for a drug are used, the higher the purity, the better.
  • the skim cake of olive is extracted with an ethanol solution, concentrated by drying, and then purified by chromatography. Tablets containing maslinic acid in an amount of 80% by mass or more.
  • a powder 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.
  • the defatted olive cake is extracted with an ethanol solution, concentrated by drying, and then purified by chromatography to obtain maslinic acid in an amount of 0.01 kg / L or more. And injectables.
  • the oily lees of Saito Reeb is extracted with an ethanol solution, concentrated by drying, and then contains 0.7% by mass or more of maslinic acid purified by chromatography. Tablets.
  • the extraction residue of olive is extracted with an ethanol solution, concentrated by drying, and then purified by chromatography. And tablets containing the following.
  • oily cake of olive is extracted with an ethanol solution, concentrated by drying, and then contains at least 1% by mass of maslinic acid purified by chromatography and persolic acid. Powder.
  • the defatted olive cake is extracted with an ethanol solution, concentrated by drying, and then purified by chromatography. And a capsule containing the same.
  • Examples of the pentacyclic triterpene used in the examples include erythrodiol (Funakoshi), ursolic acid (Wako Pure Chemical), Baol (Funakoshi), bery phosphoric acid (Funakoshi), and veline. (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 will be described below with reference to an actual example. The maslinic acid used was extracted and purified from an orifice plant and 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) of silica gel.
  • the crude maslinic acid fraction was purified by ⁇ DS column chromatography using a column packed with about 30 times (60 g) of octadecylsili gel.
  • vacuum drying was performed to obtain 1.51 g of purified maslinic acid 1.
  • the concentrate was fractionated by silica gel column chromatography using a column packed with about 40 times (500 g) of 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.
  • this extract was subjected to silica gel column chromatography using a column packed with about 40 times (1400 g) silica gel.
  • this purified maslinic acid 3 is a part of this purified maslinic acid in a sodium salt and a potassium salt state, and the remaining most is a free acid state It was confirmed. Their 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. ⁇ Synthesis Example 1> Ethyl maslinate
  • maslinic acid 1.0 g was dissolved in 20 OmL of anhydrous dimethylformamide, and 144.
  • Omg of imidazole and 35 OciL of triethylsilyl chloride were added at 0 ports, sealed, and stirred for 2 hours.
  • 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. Add and release was placed.
  • erythrodiol 5.0 g was dissolved in 250 mL of pyridine, 100 mL of acetic anhydride was added, and the mixture was stirred for 10 minutes. After distilling off pyridine and acetic anhydride, the residue was dissolved in ether, and the ether phase was washed once with a 1N aqueous hydrochloric acid solution, once with a saturated sodium hydrogen carbonate solution and three times with pure water, and then magnesium sulfate was removed. In addition, it was left overnight.
  • AlamarBlue 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.
  • the control group was a group to which only the solvent in which the pentacyclic triterpene was dissolved was used as the control group, and the test intensity was 100% when the fluorescence intensity obtained in the control group was 100%.
  • the growth inhibition rate was calculated from the fluorescence intensity of the substance-added group. That is, Equation 1 is as follows.
  • Table 1 shows the results as the growth inhibition rate.
  • maslinic acid, erythrodiol, ursolic acid, ebaol, veric acid, veline, their physiologically acceptable salts and their derivatives have extremely excellent vascular smooth muscle cell growth inhibitory effects. It has become clear to have.
  • Radzuto derived from 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 counted 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 migrate the cells. The suppression 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.
  • the migration inhibition rate was calculated. That is, Equation 2 is satisfied. ⁇ Formula 2>
  • Migration inhibition rate (%) 100-(number of cells in test substance-added group / number of cells in control group) X 100
  • the vascular smooth muscle cell migration inhibitory effect was evaluated by the above method.
  • the results are shown in Table 2 as the migration suppression rate.
  • Wistar female rats (15-week-old) were pre-bred for 1 week on a powdered diet with AIN-93 composition and divided into 8 groups (4 animals per group). Under ventral valpital anesthesia, 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 the balloon to the external artery while rotating. 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 once a day at a dose of 20 mg / kg by gavage using a sonde.
  • Equation 3 is as follows. ⁇ Equation 3>
  • Intimal hyperplasia suppression rate (%) 100-(area ratio of test substance administration group / area ratio of control group) X 100
  • the intimal thickening inhibitory effect was evaluated by the above method. The results are shown in Table 3 as the intimal hyperplasia inhibition rate.
  • Table 3 shows that the evaluated maslinic acid, erythrodiol, ursolic acid, ethanol, berylic acid, berylin, their physiologically acceptable salts and their derivatives have the following effects: It was found to have.
  • NZW ⁇ herons male, 2-2.5 kg were pre-fed for 1 week on a powdered diet (cholesterol diet) with AIN-93 composition containing 1% cholesterol. Each group was divided into 5 birds) and bred on a cholesterol diet containing 1% of each of the test substances shown in Table 3 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.
  • the cells were stained with SudanlV, and the total area of the aortic lumen and the area of atherosclerotic lesion were measured by analyzing images taken with a digital camera (manufactured by Olympus) under a microscope.
  • 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) X 1 0 0
  • the anti-atherosclerosis inhibitory effect was evaluated by the above method. The results are shown in Table 4 as the arteriosclerosis inhibition rate
  • the acute toxicity test was performed by the following method. Wistar female rats (6-week-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 / group) were brought to an even body weight. ) And maslinic acid-administered group, erythrodiol-administered group, ursolic acid-administered group, ebaol-administered group, bevulinic acid-administered group, and beverin-administered group. Each test substance was suspended in cottonseed oil and orally administered by force using a sonde so that the weight became 2000 mg mg and body weight kg. Subsequently, the animals were bred on a powdered feed with AIN-93 composition, the prognosis was observed two weeks after the administration, and two weeks later, the internal organs were examined by dissection.
  • each pentacyclic triterpene is more than 200 mg / kg of body weight, which is extremely excellent in safety, and is taken orally as a form of drug for vascular disorders It turns out that it is also possible.
  • Og Carboxymethylcellulose calcium 10.5mg At the above mixing ratio, mix well each substance, and press this mixture into tablets to make one tablet 30 Omg tablets I got Example 7 powder
  • Purified maslinic acid 2 10. Omg lactose 981. Omg hydroxypropylcellulose 4. Omg Soft caffeic anhydride 5. Omg In the above ratio of 3 cocks, first thoroughly mix purified maslinic acid 2 and lactose and then add hydroxy. Propyl cellulose was added and granulated. This was dried, granulated, and mixed with soft silica anhydride to obtain a powder.
  • Example 8 Capsules
  • Omg Capsules were obtained by filling the capsules well mixed with the above ingredients in the above mixing ratio.
  • Purified maslinic acid 2 10. Omg Persolic acid 20. Omg Lactose 961. Omg Hydroxypropylcellulose 4. Omg Soft cake anhydride 5. Omg At the above ratio, purified maslinic acid 2, ursolic acid and lactose After mixing well, hydroxypropylcellulose was added and granulated. This was dried, granulated, and mixed with soft caieic anhydride to obtain a powder.
  • maslinic acid 1 10. Omg erythrodiol 50. Omg lactose 128. Omg corn starch 69. Omg magnesium stearate '3. Omg A capsule was obtained. According to the agent for a vascular disease of the present invention, maslinic acid, erythrodiol, ursolic acid, ebaol, vertulinic acid, perrin, their physiologically acceptable salts and their derivatives can be used for vascular smoothing.
  • Anti-muscular cell proliferation and / or vascular smooth muscle cell migration inhibitory effects anti-cell proliferative vascular lesion effects such as intimal hyperplasia inhibition and anti-atherosclerosis, anti-vascular such as anti-atherosclerosis and anti-restenosis after PTCA It has excellent disability and disease effects, Since it is of natural origin, it can impart a sense of security and safety, and is more suitable for various formulations, and can particularly enjoy these effects.

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Abstract

L'invention concerne des médicaments pour une lésion vasculaire contenant, en tant que principe(s) actif(s), un ou plusieurs éléments sélectionnés dans acide maslinique, érythrodiol, acide ursolique, uvaol, acide bétulinique, leurs sels et dérivés acceptables sur le plan physiologique; ainsi que des matériaux de départ provenant de ces composés.
PCT/JP2002/003189 2001-03-30 2002-03-29 Medicaments pour une lesion vasculaire WO2002078685A1 (fr)

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WO2003057224A1 (fr) * 2001-12-28 2003-07-17 The Nisshin Oillio, Ltd. Inducteur d'apoptose
WO2009121992A2 (fr) 2008-04-03 2009-10-08 Biomaslinic S.L. Utilisation de l'acide maslinique dans le traitement de pathologies et de leurs symptômes par inhibition de cox-2
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
EP2440222A4 (fr) * 2009-06-12 2012-12-12 Generex Pharm Inc Compositions et méthodes pour prévenir et traiter des pathologies et des maladies cérébrales
JP7429066B2 (ja) 2011-05-10 2024-02-07 丸善製薬株式会社 Ｔｉｅ２活性化剤、血管の成熟化剤、血管の安定化剤、飲食品、及び外用剤

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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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
KR102757622B1 (ko) * 2017-09-13 2025-01-21 엠욘 인코퍼레이티드 우르솔산 모르폴린 및 디에탄올아민 염

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04164029A (ja) * 1990-10-29 1992-06-09 Nippon Oil & Fats Co Ltd 活性酸素障害防御剤
JPH07258098A (ja) * 1994-03-24 1995-10-09 Toray Ind Inc エンドセリン受容体結合阻害剤
JPH0920674A (ja) * 1995-07-11 1997-01-21 Lotte Co Ltd 喉炎症起因菌に対する抗菌活性および溶血毒阻害活性を有する口腔用製剤
JPH0967249A (ja) * 1995-06-22 1997-03-11 Nippon Flour Mills Co Ltd グリセロリン酸脱水素酵素阻害剤
EP0810217A1 (fr) * 1996-05-29 1997-12-03 Japan Energy Corporation Dérivés de pyrazole et leur utilisation pharmaceutique comme inhibiteurs de la croissance des cellules des muscles lisses
WO1998004331A1 (fr) * 1996-07-25 1998-02-05 Universidad De Granada Procede de recuperation industrielle des acides oleanolique et maslinique contenus dans les sous-produits de la mouture d'olive
JPH10182627A (ja) * 1996-12-20 1998-07-07 Sankyo Co Ltd 新規化合物Ｓ−１５１８３ａ及びＳ−１５１８３ｂ
JPH10265328A (ja) * 1997-03-27 1998-10-06 Nippon Flour Mills Co Ltd 化粧料、ペットフード、リパーゼ阻害剤及びそれを含む食品
JP2000136130A (ja) * 1998-10-30 2000-05-16 Coral Biotech Kk ヒスタミン遊離抑制剤
JP2000159673A (ja) * 1998-11-27 2000-06-13 Taisho Pharmaceut Co Ltd 形質転換増殖因子β阻害剤
JP2000191535A (ja) * 1998-12-25 2000-07-11 Nippon Soda Co Ltd 血管平滑筋細胞増殖に起因する疾患用薬
JP2000256392A (ja) * 1999-03-08 2000-09-19 Pola Chem Ind Inc トリテルペン及びこれを含有するａｃａｔ阻害剤
JP2001055375A (ja) * 1999-08-13 2001-02-27 Taisho Pharmaceut Co Ltd Ｅ型プロスタグランジン誘導体
JP2001181632A (ja) * 1999-10-14 2001-07-03 Nisshin Oil Mills Ltd:The 抗酸化剤
JP2001213778A (ja) * 2000-02-03 2001-08-07 Pola Chem Ind Inc 負荷ストレス軽減剤及びそれを含有する皮膚外用剤

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000044478A (ja) * 1998-07-28 2000-02-15 Pola Chem Ind Inc Ａｃａｔ阻害剤及びこれを含有する動脈硬化の予防・治療用の組成物
JP2001252054A (ja) * 2000-01-07 2001-09-18 Kanebo Ltd 食品組成物

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04164029A (ja) * 1990-10-29 1992-06-09 Nippon Oil & Fats Co Ltd 活性酸素障害防御剤
JPH07258098A (ja) * 1994-03-24 1995-10-09 Toray Ind Inc エンドセリン受容体結合阻害剤
JPH0967249A (ja) * 1995-06-22 1997-03-11 Nippon Flour Mills Co Ltd グリセロリン酸脱水素酵素阻害剤
JPH0920674A (ja) * 1995-07-11 1997-01-21 Lotte Co Ltd 喉炎症起因菌に対する抗菌活性および溶血毒阻害活性を有する口腔用製剤
EP0810217A1 (fr) * 1996-05-29 1997-12-03 Japan Energy Corporation Dérivés de pyrazole et leur utilisation pharmaceutique comme inhibiteurs de la croissance des cellules des muscles lisses
WO1998004331A1 (fr) * 1996-07-25 1998-02-05 Universidad De Granada Procede de recuperation industrielle des acides oleanolique et maslinique contenus dans les sous-produits de la mouture d'olive
JPH10182627A (ja) * 1996-12-20 1998-07-07 Sankyo Co Ltd 新規化合物Ｓ−１５１８３ａ及びＳ−１５１８３ｂ
JPH10265328A (ja) * 1997-03-27 1998-10-06 Nippon Flour Mills Co Ltd 化粧料、ペットフード、リパーゼ阻害剤及びそれを含む食品
JP2000136130A (ja) * 1998-10-30 2000-05-16 Coral Biotech Kk ヒスタミン遊離抑制剤
JP2000159673A (ja) * 1998-11-27 2000-06-13 Taisho Pharmaceut Co Ltd 形質転換増殖因子β阻害剤
JP2000191535A (ja) * 1998-12-25 2000-07-11 Nippon Soda Co Ltd 血管平滑筋細胞増殖に起因する疾患用薬
JP2000256392A (ja) * 1999-03-08 2000-09-19 Pola Chem Ind Inc トリテルペン及びこれを含有するａｃａｔ阻害剤
JP2001055375A (ja) * 1999-08-13 2001-02-27 Taisho Pharmaceut Co Ltd Ｅ型プロスタグランジン誘導体
JP2001181632A (ja) * 1999-10-14 2001-07-03 Nisshin Oil Mills Ltd:The 抗酸化剤
JP2001213778A (ja) * 2000-02-03 2001-08-07 Pola Chem Ind Inc 負荷ストレス軽減剤及びそれを含有する皮膚外用剤

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057224A1 (fr) * 2001-12-28 2003-07-17 The Nisshin Oillio, Ltd. Inducteur d'apoptose
WO2009121992A2 (fr) 2008-04-03 2009-10-08 Biomaslinic S.L. Utilisation de l'acide maslinique dans le traitement de pathologies et de leurs symptômes par inhibition de cox-2
EP2440222A4 (fr) * 2009-06-12 2012-12-12 Generex Pharm Inc Compositions et méthodes pour prévenir et traiter des pathologies et des maladies cérébrales
US9050277B2 (en) 2009-06-12 2015-06-09 Generex Pharmaceuticals, Inc. Combined Geum japonicum and Centella asiatica extracts for the therapeutic treatment of heart failure
US9283255B2 (en) 2009-06-12 2016-03-15 Generex Pharmaceuticals, Inc. Compositions and methods for the prevention and treatment of red blood cell coagulation
US9629884B2 (en) 2009-06-12 2017-04-25 Generex Pharmaceuticals, Inc. Compositions and methods for increasing lifespan and health span
US9950019B2 (en) 2009-06-12 2018-04-24 Generex Pharmaceuticals, Inc. Compositions and methods for the prevention and treatment of brain diseases and conditions
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
JP7429066B2 (ja) 2011-05-10 2024-02-07 丸善製薬株式会社 Ｔｉｅ２活性化剤、血管の成熟化剤、血管の安定化剤、飲食品、及び外用剤

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