WO2006082743A1 - Agent therapeutique - Google Patents

Agent therapeutique Download PDF

Info

Publication number
WO2006082743A1
WO2006082743A1 PCT/JP2006/301200 JP2006301200W WO2006082743A1 WO 2006082743 A1 WO2006082743 A1 WO 2006082743A1 JP 2006301200 W JP2006301200 W JP 2006301200W WO 2006082743 A1 WO2006082743 A1 WO 2006082743A1
Authority
WO
WIPO (PCT)
Prior art keywords
present
active ingredient
action
treatment
derivatives
Prior art date
Application number
PCT/JP2006/301200
Other languages
English (en)
Japanese (ja)
Inventor
Tatsuji Enoki
Yoko Kudo
Katsumi Sugiyama
Hiromu Ohnogi
Hiroaki Sagawa
Ikunoshin Kato
Original Assignee
Takara Bio Inc.
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 Takara Bio Inc. filed Critical Takara Bio Inc.
Priority to JP2007501541A priority Critical patent/JPWO2006082743A1/ja
Publication of WO2006082743A1 publication Critical patent/WO2006082743A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A61K31/37—Coumarins, e.g. psoralen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P9/10—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

Definitions

  • the present invention is useful for the treatment or prevention of diseases requiring an antifoaming action of cells and an inhibitory action of Z or acyl CoA cholesterol transferase, such as arteriosclerosis and hyperlipidemia, in the treatment or prevention.
  • diseases requiring an antifoaming action of cells and an inhibitory action of Z or acyl CoA cholesterol transferase such as arteriosclerosis and hyperlipidemia, in the treatment or prevention.
  • Z or acyl CoA cholesterol transferase such as arteriosclerosis and hyperlipidemia
  • arteriosclerosis, hyperlipidemia, hypertension, and diabetes have been accompanied by changes in dietary habits that are rich in high-calorie and high-cholesterol diets, and an increase in the age group due to an increase in life expectancy.
  • the increase in so-called lifestyle-related diseases is rapidly increasing and has become a major social problem.
  • the fatty streak eventually becomes a fibrous hard spot and protrudes into the vascular wall, and as the lesion progresses further, calcification and thrombus attachment accompany the narrowing of the blood vessel cavity, and the hard spot breaks down causing thrombotic occlusion.
  • hard plaques contain a large amount of lipid components such as cholesterol esters, which are easy to break. Therefore, by suppressing the foaming of macrophages, such as vascular smooth muscle cells, and inhibiting the activity of acyl-CoA cholesterol cholesterol-mediated transferase, the stabilization and regression of atherosclerotic lesions can be achieved.
  • button bow fu has a cancer suppressive effect (eg, Non-patent Document 1), a disaccharide-degrading enzyme inhibitory action (eg, Patent Document 1), an antioxidant action (eg, Patent Document 2, Non-patent Document 2). It is also known that it has the ability to activate cells (for example, Patent Document 2) and suppress melanin production (for example, Patent Document 2).
  • Non-Patent Document 3 As a characteristic chemical component contained in button bow fu, a plurality of types of coumarin derivatives are known, and their tumor promoter suppression action and the like have been studied (for example, Non-Patent Document 3).
  • Patent Document 1 JP 2003-26694 A
  • Patent Document 2 JP 2004-26697 A
  • Non-Patent Document 1 T. Morioka and 8 others, Cancer Letters, 2004, Vol. 205, pl33-141
  • Non-Patent Document 2 M. Hisamoto and 2 others, Agric. Food Chem., 2004, Vol. 5 2, p445 -450
  • Non-Patent Document 3 B. Fan and 5 others, Journal of Japanese Botany, 2000, Vol. 7 5, No. 4, p257-261
  • An object of the present invention is to develop a safe and easily ingestible substance that has a cell antifoaming action suitable as a food material and a pharmaceutical material, and uses the composition or the substance. To provide food or feed.
  • the first invention of the present invention is characterized in that it contains a processed product derived from button bow as an active ingredient, and the anti-foaming action of cells in treatment or prevention and Z Or, it requires an inhibitory effect on the acyl CoA cholesterol acyltransferase
  • the present invention relates to a therapeutic or preventive agent for diseases.
  • a second invention of the present invention relates to an antifoaming agent for cells, characterized by containing a processed product derived from button bow as an active ingredient.
  • a third invention of the present invention relates to an acyl CoA cholesterol acyltransferase inhibitor, characterized by containing a processed product derived from button bowfish as an active ingredient.
  • a fourth invention of the present invention comprises a processed product derived from button bow fu as an active ingredient, for cell antifoam and for inhibiting Z or acyl CoA cholesterol acyltransferase. Relating to food or feed.
  • the fifth invention of the present invention is selected from the group consisting of 3, -acetoxyl 4, mono-senecyoxyoxy 3, 4, 4-zino, idroseserine, derivatives thereof and pharmaceutically acceptable salts thereof.
  • the sixth invention of the present invention is selected from the group consisting of 3, -acetooxy 4 'senesioxyloxy 3', 4'-dino, idroseserine, derivatives thereof and pharmaceutically acceptable salts thereof.
  • the present invention relates to a cell antifoaming agent characterized by containing one or more active ingredients.
  • the seventh invention of the present invention is selected from the group consisting of 3, -acetoxy 4 ′ senesioxyloxy 3 ′, 4′-dino, idrothelin, derivatives thereof and pharmaceutically acceptable salts thereof.
  • the present invention relates to an isyl CoA cholesterol transferase inhibitor characterized by containing one or more active ingredients.
  • the eighth invention of the present invention is selected from the group consisting of 3, -acetoxy-4, mono-senecyoxyoxy 3, 4, 4-zino, idroseserine, derivatives thereof and pharmaceutically acceptable salts thereof.
  • the present invention relates to a food or feed for anti-foaming of cells and / or for inhibition of acyl-CoA cholesterol acyltransferase.
  • the ninth invention of the present invention is that a subject is administered with an effective amount of a processed product derived from button bow.
  • the present invention relates to a method for treating or preventing a disease requiring an antifoaming action of a cell and an inhibitory action of Z or acyl CoA cholesterol acyltransferase for treatment or prevention.
  • the tenth invention of the present invention is for the manufacture of a therapeutic or prophylactic agent for a disease requiring an antifoaming action of cells and an inhibitory action of Z or acyl CoA cholesterol acyltransferase in the treatment or prevention. It relates to the use of processed products derived from button bow.
  • the eleventh invention of the present invention provides a subject with an effective amount of 3'-acetoxy 4 'seneciyloxy-3,4, -dinoidoid roseserin, a derivative thereof, and a pharmaceutically acceptable salt thereof.
  • the present invention relates to a method for treating or preventing a disease requiring an antifoaming action of a cell and an inhibitory action of Z or acyl CoA cholesterol acyltransferase, including administering one or more selected from a group that also has strength. .
  • the twelfth invention of the present invention is for the manufacture of a therapeutic or prophylactic agent for a disease requiring an anti-foaming action of a cell and an inhibitory action of Z or acyl CoA cholesterol acyltransferase in the treatment or prevention. 3, -acetoxy-4, -senesioyloxy-3,4, -dinohydrodroserine, its derivatives and pharmaceutically acceptable salts thereof.
  • a medicament, food or feed for treating or preventing a disease requiring an antifoaming action of cells and an inhibitory action of Z or acyl Co A cholesterol acyltransferase in the treatment or prevention.
  • the medicament is useful for arteriosclerosis, hyperlipidemia, and diseases caused thereby.
  • the food of the present invention is a functional food useful for maintaining the homeostasis of the living body by the antifoaming action of cells and the inhibitory action of Z or acyl CoA cholesterol acyltransferase.
  • Cell foaming is caused by accumulation of cholesterol ester in the cell.
  • the anti-foaming action of the cells can be easily measured by using an assay system with the amount of cholesterol ester in the cells as an index as described in Example 1 described later. That is, by culturing macrophages in the presence of a test substance and acetyl LDL and evaluating the amount of cholesterol ester in the cells, the antifoaming action of the cells can be easily measured.
  • the cells to be antifoamed are not particularly limited, and examples thereof include vascular cells such as macrophages and smooth muscle cells, and blood cells.
  • Acyl CoA cholesterol acyltransferase also known as acyl CoA: cholesterol O-acyltransferase, hereinafter also abbreviated as ACAT
  • ACAT cholesterol O-acyltransferase
  • transfers long-chain fatty acids from cholesterol acyl to cholesterol It is an enzyme that catalyzes ester synthesis.
  • the ACAT inhibitory action can be easily measured using an assay system as described in Example 2 described later. That is, by mixing a test substance and an enzyme source containing ACAT, and evaluating the transfer of the Oleoyl group from radiolabeled Oleoyl-CoA to cholesterol, the ACAT inhibitory action can be easily measured.
  • the button bow fu used in the present invention is not particularly limited, and fruits, seeds, seed coats, flowers, leaves, stems, roots, rhizomes and Z, or whole plants can be used as they are.
  • the processed product derived from buttonbow fu (hereinafter sometimes referred to as the processed product of the present invention) used as an active ingredient of the present invention is a raw material plant that has been subjected to some processing and is a cell
  • the processed product of the present invention used as an active ingredient of the present invention is a raw material plant that has been subjected to some processing and is a cell
  • There is no particular limitation as long as it has antifoaming action and Z or ACAT inhibitory action but for example, extract, pulverized product, juice, crushed product, chemically treated product, enzyme treated product, particularly preferably Examples are extracts, pulverized products and juices.
  • the treated product of the present invention is particularly preferably a cell anti-foaming agent and an ACAT inhibitory agent described later 3, -acetoxyl 4, monosenecioinoxy 3, 4, 4, 4, A treated product containing a high content of cerine can be used.
  • high content means that 3, 4-acetoxy 4 in the raw material plant, 3, 4-acetoxyyloxy 3, 4, 4-dihydroceserine contained in the treated product 3, 4-acetoxy 4 , 1 Senesioiloxy 3, 4, 4-means that the concentration of Gino and Idoloserine is high, and it is preferably 1.5 times or more of the concentration in buttonbow, more than 2 times more preferable.
  • an extract refers to an extraction operation performed on an original plant using an extraction solvent. It refers to the substance itself obtained through the process. Extraction can be carried out by a known extraction method as follows. For example, after pulverizing or chopping the raw material, it can be carried out batchwise or continuously using a solvent.
  • the extraction solvent for obtaining the extract is not particularly limited, but water, glycerol, glycols (ethylene glycol, propylene glycol, etc.), alcohols (ethanol, methanol, isopropyl alcohol, etc.), ketones (acetone, Methylethyl ketone, etc.) and hydrophilic or lipophilic solvents (black mouth form, methyl acetate, ethyl acetate, etc.) can be mentioned, and they can be used alone or as a mixture as desired.
  • Examples of using the mixed solution as an extraction solvent are not particularly limited, but various aqueous solutions can be used, for example, 10 to 95%, preferably 15 to 90%, more preferably 20 to 85% alcohol. An aqueous solution can be used.
  • the amount of the extraction solvent may be determined as appropriate, but it is generally preferably 0. What is necessary is just to use 1-100 times amount extraction solvent.
  • the extraction temperature may be appropriately determined according to the purpose, but in the case of water extraction, it is usually preferably 4 to 130 ° C, more preferably 25 to: LOO ° C. When ethanol is contained in the solvent, a temperature range of 4 to 60 ° C. is preferable from the viewpoint of safety.
  • the extraction time may be determined in consideration of the extraction efficiency, but usually the raw material, extraction solvent, and extraction temperature are set to be preferably in the range of several seconds to several days, more preferably 5 minutes to 24 hours. It is preferable to do this.
  • the extraction operation may be performed, for example, with stirring or standing, and may be repeated several times as necessary.
  • an extract derived from button bow fu used in the present invention hereinafter sometimes referred to as the extract of the present invention
  • the extract is treated by filtration, centrifugation, concentration, ultrafiltration, molecular sieving, etc., so that the cell antifoaming agent or ACAT inhibitory agent, such as 3, -acetoxy-4, described below, can be obtained.
  • An extract enriched with one-senecyoxy3,4, -dihydroserine can be prepared.
  • the cell antifoaming action and ACAT inhibitory action of the extract or concentrated extract can be easily measured by the methods described in Examples 1 and 2 described later.
  • the button bow used in the present invention is a known method. If an extract using the same has an antifoaming effect on cells and a Z or ACAT inhibitory effect, it can be used as the extract of the present invention. It is also possible to use two or more of the above extracts. It is also possible to use two or more extracts obtained by extraction methods with different raw plant power.
  • the extraction of the present invention also applies to a fraction obtained by fractionating the extract of the present invention by a known method and a fraction obtained by repeating the fractionation operation a plurality of times. It is included in the thing.
  • the fractionation means include extraction, fractional precipitation, column chromatography, thin layer chromatography and the like.
  • the processed product derived from the button bow used in the present invention includes, for example, a powdered product derived from the button bow used in the present invention (hereinafter referred to as the present invention). May be referred to as a pulverized product of the invention).
  • a powdered product derived from the button bow used in the present invention hereinafter referred to as the present invention.
  • Examples of the method for producing a pulverized product of the present invention include a method of obtaining a pulverized product derived from a button-shaped button bow by drying a plant and using a pulverizer. Further, a pulverized product may be obtained by freeze pulverization.
  • the squeezed juice derived from button bow fu used in the present invention can also be used as the treated product of the present invention.
  • the method for producing the juice is not particularly limited as long as it is a known method for squeezing a plant.
  • the juice can be squeezed using a screw type, gear type, cutter type or other squeezer or juicer.
  • the juice can be obtained by chopping or grinding and squeezing with the above-mentioned juicer or cloth.
  • the crushed material is a material obtained by pulverizing a raw plant, and generally has a larger tissue piece than the pulverized material, and can be produced, for example, by using a crusher.
  • the chemical treatment product is not particularly limited, but refers to a product obtained by subjecting the plant to acid treatment, alkali treatment, oxidation treatment, reduction treatment, etc., for example, hydrochloric acid, sulfuric acid, nitric acid, citrate, It can be produced by immersing the raw material plant in an aqueous solution containing an inorganic or organic acid such as acetic acid, or an inorganic or organic base such as sodium hydroxide, potassium hydroxide or ammonia.
  • Chemically treated products include all those derived from plants that have undergone chemical treatment as described above. Fermentation An untreated product refers to, for example, an enzyme-treated product such as pectinase, cellulase, xylanase, amylase, mannanase, and dalcosidase, and an enzyme-reacted product (eg, fermented product) from microorganisms. Can be produced by acting in a suitable buffer. Enzyme-treated products include all those derived from plants that have been subjected to the enzyme treatment as described above. Further, the processed product derived from the button bow of the present invention includes, for example, a juice obtained by cutting a stem of a raw material plant and obtaining the cut surface.
  • the shape of the treated product of the present invention is particularly limited as long as it can exhibit an antifoaming action of cells and a Z or ACAT inhibitory action when used as an active ingredient in each aspect of the present invention.
  • it may be in the form of powder, solid or liquid.
  • the treated product can be granulated by a known method and used as a granular solid.
  • the granulation method is not particularly limited, but rolling granulation, stirring granulation, fluidized bed granulation, air flow granulation, extrusion granulation, compression molding granulation, pulverization granulation, spray granulation, spray granulation or spraying Examples include granulation.
  • the treated product in a powder form can be dissolved in a liquid, for example, water or alcohol, to obtain a liquid and used as a treated product derived from the button bow of the present invention.
  • 3'-acetoxy which will be described later, is preferably used as the treated product of the present invention.
  • -4 'Senesyl oiloxy 3', 4'-dinoidoid roseserine is a processed product containing a high amount of the compound, and from the viewpoint of further serving as edible, for example, ethanol extract, water-containing ethanol extraction Products, hot water extracts, glycerol extracts or water-containing glycerol extracts, glycol extracts such as ethylene glycol and propylene glycol, water-containing dallicol extracts, and pulverized products are preferred.
  • a derivative for example, an ester or the like is easily hydrolyzed in the body to produce the above-mentioned 3, -acetooxy-4, mono-senecioinoleoxy 3,4, -dihydroserine
  • Derivatives (prodrugs) that can exhibit the desired effect can be prepared. Preparation of a strong prodrug may be performed according to a known method.
  • derivatives obtained by metabolizing the compound of the present invention to a mammal are also included in the derivatives of the present invention.
  • the powerful derivative may be a salt of 3, -acetoxy-4, -senesioyloxy-3,4, -dihydroserine.
  • the 3,1-acetoxy-1,4-senesinoinoreoxy-1,4, -dino and idrothelin according to the present invention are their derivatives and their derivatives as long as the desired effects of the present invention can be obtained. It also includes salts.
  • various isomers such as optical isomers of 3'-acetoxy-4'-senecioyloxy 3,4, monozinoidroseserine, ketoeenol tautomers and geometric isomers, and isomers were isolated. Can be used in the present invention as long as they have anti-foaming action or ACAT inhibitory action on cells.
  • Examples of the salt used in the present invention include alkali metal salts, alkaline earth metal salts, salts with organic bases, and the like.
  • the pharmaceutically acceptable salt used in the present invention means a salt of a compound that is substantially nontoxic to living organisms and has an antifoaming action on cells.
  • Such salts include, for example, sodium, potassium, calcium, magnesium, ammonium or protonated benzathine (N, N'-dibenzylethylenediamine), choline, ethanolamine, diethanolamine.
  • salts such as amine, ethylenediamine, megramin (N-methyldalcumamine), venetamine (N-benzylphenethylamine), piperazine or tromethamine (2-amino-2-hydroxymethyl-1,3-propanediol).
  • the treated product of the present invention and 3'-acetoxy 4'-senesyloxy-3 ', 4'-dihydroserine, a derivative thereof and / or a pharmaceutically acceptable salt thereof Is referred to as an active ingredient of the present invention, and a therapeutic or preventive agent for a disease requiring an antifoaming action and a Z or ACAT inhibitory action of a cell containing the active ingredient of the present invention is referred to as a therapeutic or preventive agent of the present invention.
  • a therapeutic or preventive agent of the present invention is referred to as a therapeutic or preventive agent of the present invention.
  • the cell antifoaming agent and ACAT inhibitor described later are included.
  • the active ingredient of the present invention is derived from button bow fu which has been edible since ancient times, and is compared with a synthetic compound having an ACAT inhibitory activity known so far (for example, FR179254 described later). However, since it is highly safe, there is no particular toxicity as described later, and there is no risk of side effects. Therefore, the disease can be treated or prevented safely and appropriately. Therefore, the therapeutic agent, prophylactic agent, food or feed of the present invention comprising the active ingredient is effective for the treatment or prevention of diseases requiring anti-foaming action and ACAT inhibitory action of cells, and particularly easily. Useful as a health food ingredient that can be ingested
  • the disease requiring an anti-foaming action of cells for treatment or prevention is a disease that exhibits a therapeutic or preventive effect by suppressing cell foaming.
  • arteriosclerosis a disease caused by this, for example, Ischemic heart disease, acute myocardial infarction, unstable angina, sudden ischemic death, cerebrovascular disorder, chronic obstructive arteriosclerosis, myocardial infarction, angina, cerebral infarction, subarachnoid hemorrhage, obesity, etc. (See, for example, O'Rourke et al., J. Biol. Chem., 2002, 277 (45), 42557-4 2562).
  • the disease that requires an ACAT inhibitory action for treatment or prevention is not particularly limited.
  • the disease that requires an anti-foaming action of cells for the treatment or prevention is not limited.
  • examples include hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, multiple risk factor syndrome, or diseases caused by these factors (eg, O'Rourke et al., Biol. Chem., 2002, 277 (45), 42557—42562, Ohishi et al., Biol. Pharm. Bull., 2003, 26 (8), 1125—1128, and Ohishi et al., Chem. Pharm. Bull., 2001, 49 (7) , 830-839).
  • Examples of the therapeutic or prophylactic agent of the present invention include those prepared by combining the above-mentioned active ingredient according to the present invention with a known pharmaceutical carrier.
  • the active ingredient can be used for other ingredients that can be used for the same purpose as the active ingredient, for example, known hyperlipidemia and arteriosclerosis treatment or prevention action.
  • HMG-CoA reductase inhibitors such as stava compounds such as pravastatin, simpastatin, flupastatin, cerivastatin, atorvastatin, antifoaming agents such as fucoidan, ACAT inhibitors such as melinamide, cholesterol Ester transfer protein (CET P) inhibitor, cholesterol absorption inhibitor, squalene synthase inhibitor, LDL oxidation inhibitor, microsomal triglyceride transfer protein (MTP) inhibitor, apolipoprotein A1 production promoter, ATP—binding Cassette subfamily Al (ABCA1) inducer, squalene epoxidase inhibitor, choles Bile acid binding ⁇ Ramin such, Fuibureto system such Kurofu Ibureto, nicotinic acid, such as Naiashin, may be blended with such triglyceride lowering agent such as Ikosapento acid Echiru.
  • stava compounds such as pravastatin, simpa
  • the therapeutic agent or prophylactic agent of the present invention is usually produced by blending the active ingredient with a pharmaceutically acceptable liquid or solid carrier, and optionally, a solvent, a dispersant, an emulsifier, Add buffers, stabilizers, excipients, binders, disintegrants, lubricants, etc., solids such as tablets, condyles, powders, powders, capsules, etc., ordinary solutions, suspensions, emulsions And so on can do. Further, it can be made into a dry product that can be made liquid by adding a suitable carrier before use, or other external preparations.
  • the pharmaceutical carrier can be selected according to the administration form and formulation form of the therapeutic or prophylactic agent.
  • an oral preparation comprising a solid composition
  • it can be a tablet, pill, capsule, powder, fine granule, granule, etc., for example, starch, lactose, sucrose, mant, carboxymethylcellulose
  • Pharmaceutical carriers such as corn starch and inorganic salts are used.
  • a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a corrigent, a colorant, a fragrance and the like can be further added.
  • a sugar coating such as sucrose, gelatin or hydroxypropylcellulose, or a film of a gastric or enteric substance, if desired.
  • a pharmaceutically acceptable emulsion, solution, suspension, syrup, etc. for example, purified water, ethanol or the like as a carrier.
  • auxiliary agents such as wetting agents and suspending agents, sweetening agents, flavoring agents, preservatives and the like may be added.
  • distilled water for injection physiological saline, aqueous dextrose solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil, and the active ingredient of the present invention as a diluent according to a conventional method It can be prepared by dissolving or suspending in corn oil, propylene glycol, polyethylene glycol or the like, and adding a bactericidal agent, stabilizer, tonicity agent, soothing agent, etc., if necessary.
  • a solid composition can be produced and used by dissolving in sterile water or a sterilized solvent for injection before use.
  • the external preparation includes solid, semi-solid or liquid preparations for transdermal administration or transmucosal (intraoral or intranasal) administration. Also included are suppositories and the like. For example, emulsions such as emulsions and mouth preparations, external tinctures, liquid preparations such as liquids for transmucosal administration, ointments such as oil-based ointments and hydrophilic ointments, transdermal such as film agents, tapes, and nops. It can be a patch for administration or transmucosal administration.
  • the therapeutic agent or prophylactic agent in the above-described various preparation forms can be appropriately produced by a conventional method using a known pharmaceutical carrier or the like.
  • the content of the active ingredient in such a therapeutic agent or prophylactic agent is preferably determined in consideration of its administration form and administration method. It is not particularly limited as long as the active ingredient can be administered within the dosage range described below.
  • the content of the active ingredient in the medicament of the present invention is usually about 1 to: LOO weight%.
  • the therapeutic agent or prophylactic agent of the present invention is administered by an appropriate administration method according to the preparation form.
  • the administration method is not particularly limited, and can be administered by, for example, internal use, external use or injection.
  • the therapeutic agent or prophylactic agent of the present invention when administered by injection, it can be administered, for example, intravenously, intramuscularly, subcutaneously, intradermally, and when administered externally, for example, as an external preparation such as a suppository. And may be administered by the appropriate administration method.
  • the dosage of the therapeutic agent or prophylactic agent of the present invention is appropriately set according to the formulation form, administration method, purpose of use and the age, weight, and symptoms of the patient to whom the therapeutic agent or prophylactic agent is administered, and is constant. Absent.
  • the dosage of the active ingredient contained in the preparation for example, when the processed product of the present invention is used as an active ingredient, preferably 0.1 ⁇ g to 10 gZkg body weight per day for an adult, more preferably 1 ⁇ m.
  • g to 5 gZkg body weight more preferably 10 ⁇ g to lgZkg body weight, and 3, -acetoxy-4, -senesioyloxy-3 ′, 4′-dihydroserine, its derivatives and / or pharmaceuticals as active ingredients
  • those salts acceptable in adults preferably adults per day are 0.1 ⁇ g to 5 gZkg body weight, more preferably 1 ⁇ g to 2 gZkg body weight, more preferably g to: LgZkg body weight .
  • an amount smaller than the above-mentioned dose may be sufficient or may be necessary beyond the range.
  • Administration may be carried out once or divided into several times within a desired dose range within a day. The administration period is also arbitrary. Further, the therapeutic agent or prophylactic agent of the present invention can be administered orally as it is, or can be added daily to any food.
  • the present invention also provides a cell antifoaming agent comprising the active ingredient.
  • the antifoaming agent may be the active ingredient itself or a composition containing the active ingredient.
  • the antifoaming agent includes, for example, other components that can be used in the same application as the active ingredient, for example, components having a known therapeutic or preventive action for arteriosclerosis, such as plananostatin, sympastatin, HMG-CoA reductase inhibition of statin compounds such as flupastatin, serivastatin and atorvastatin Agents, antifoaming agents for cells such as fucoidan, ACAT inhibitors such as melinamide, cholesterol ester transfer protein (CETP) inhibitors, cholesterol absorption inhibitors, squalene synthetase inhibitors, LDL oxidation inhibitors, microsomal triglycerides Transfer protein (MTP) inhibitor, apolipoprotein A1 production promoter, ATP-binding cassette subfamily Al (ABCA1) inducer, squal
  • the antifoaming agent can also be produced in the form of a reagent that is usually used according to the method for producing the therapeutic agent or prophylactic agent.
  • the content of the active ingredient in the antifoaming agent should be such an amount that the expression of the desired effect of the present invention can be obtained in consideration of the administration method and purpose of use of the antifoaming agent. There is no particular limitation.
  • the content of the active ingredient in the antifoaming agent of the present invention is usually 1 to about LOO% by weight.
  • the amount of the antifoaming agent used is not particularly limited as long as the desired effect of the present invention can be obtained.
  • it is preferably used in such an amount that the active ingredient can be administered within the dose range of the active ingredient in the therapeutic or preventive agent.
  • the administration method is not particularly limited, and may be appropriately set in the same manner as the therapeutic agent or prophylactic agent.
  • the antifoaming agent is useful in the treatment or prevention of a disease requiring an antifoaming action of a cell for the above-mentioned treatment or prevention, for example, arteriosclerosis or a disease caused by this.
  • the anti-foaming agent is also useful for screening drugs for diseases that require anti-foaming action of cells for treatment or prevention. Furthermore, the antifoaming agent is useful for studying the mechanism of arteriosclerosis and foaming of various cells, and for functional studies on physical changes of the cells. The antifoaming agent can also be added to foods or beverages.
  • the present invention also provides an ACAT inhibitor containing the active ingredient.
  • the ACAT inhibitor may be the active ingredient itself or a composition containing the active ingredient.
  • the ACAT inhibitor may be, for example, another component that can be used for the same purpose as the active ingredient, such as a known hyperlipidemia or arteriosclerosis treatment or prevention component, such as pravastatin.
  • HMG-CoA reductase inhibitors such as statins such as cerivastatin and atorvastatin, cellular antifoaming agents such as fucoidan, ACAT inhibitors such as melinamide, cholesterol ester transfer protein (CETP) inhibitors, cholesterol absorption Inhibitor, squalene synthase inhibitor, LDL oxidation inhibitor, microsomal triglyceride transfer protein (MTP) inhibitor, apolipoprotein A1 production promoter, ATP-binding cassette subfamily Al (ABCA1) inducer, squalene epoxidase It can also be combined with inhibitors, bile acid-binding rosins such as cholestyramine, fibrates such as clofibrate, nicotinic acids such as niacin, and neutral fat lowering agents such as ethyl icosapentate.
  • statins such as cerivastatin and atorvastatin
  • the ACAT inhibitor can also be produced in the form of a commonly used reagent in accordance with the method for producing the therapeutic agent or prophylactic agent.
  • the content of the active ingredient in the ACAT inhibitor is not particularly limited as long as the desired effect of the present invention can be obtained in consideration of the administration method and purpose of use of the ACAT inhibitor. There is no particular limitation.
  • the content of the active ingredient in the ACAT inhibitor of the present invention is usually 1 to about L00% by weight.
  • the amount of the ACAT inhibitor used is not particularly limited as long as the desired effect of the present invention can be obtained. In particular, when it is used after being administered to a living body, it is preferably used in such an amount that the active ingredient can be administered within the dose range of the active ingredient in the therapeutic agent or prophylactic agent.
  • the administration method is not particularly limited, and may be appropriately set in the same manner as the therapeutic agent or prophylactic agent.
  • the ACAT inhibitor is useful in the treatment or prevention of diseases requiring ACAT inhibitory action for the above-mentioned treatment or prevention, such as arteriosclerosis and hyperlipidemia, and diseases caused by these factors.
  • the ACAT inhibitor is also useful for screening drugs for diseases that require ACAT inhibitory action for treatment or prevention.
  • the ACAT inhibitor is also useful for studying the mechanism of cholesterol ester production and the mechanism for the development of the aforementioned diseases such as hyperlipidemia and arteriosclerosis.
  • the ACAT inhibitor can also be added to foods or beverages.
  • the active ingredient of the present invention is not particularly toxic as will be described later. In addition, there is no worry of side effects. Therefore, the cell antifoaming action and the Z or A CAT inhibitory action can be expressed in vivo safely and appropriately. Therefore, including the active ingredient
  • the medicament, food or feed according to the present invention comprises an antifoaming action of cells and
  • the present invention provides a food or feed for cell antifoaming and Z or ACAT inhibition comprising the active ingredient (in the present specification, referred to as the food or feed of the present invention).
  • the food or feed of the present invention has a cell anti-foaming action and a Z or ACAT inhibitory action, thereby causing a disease that requires a cell anti-foaming action and a Z or ACAT inhibitory action for treatment or prevention, ie, arteriosclerosis as described above.
  • the food or drink of the present invention is extremely useful as a functional food (specific health food, etc.) with the purpose of preventing, ameliorating or treating the above-mentioned diseases, and the blood cholesterol level is a concern. For those who are concerned about neutral fat, those who are concerned about body fat
  • the active ingredient of the present invention and other substances having an action for improving, treating or preventing hyperlipidemia and arteriosclerosis, such as known hyperlipidemia and arteries.
  • Ingredients having therapeutic or prophylactic effects on sclerosis for example, HMG-CoA reductase inhibitors such as pravastatin, sympastatin, flupastatin, cerivastatin, atorvastatin and the like, and antifoaming agents for cells such as fucoidan, melinamide ACAT inhibitor, cholesterol ester transfer protein (CETP) inhibitor, cholesterol absorption inhibitor, squalene synthase inhibitor, LDL oxidation inhibitor, microsomal triglyceride transfer protein (MTP) inhibitor, apolipoprotein A1 production promoter, ATP—binding cassette subfamily Al (ABCA1) inducer, square More effective by combining with Renepoxidase inhibitors, bile acid-binding rosins such as cholestyramine, fi
  • High food or feed can also be produced. It can also be blended with known health food materials such as ashitapa and processed products thereof, peptides, dalcomannan, chitosan, plant sterol esters, EPA, DHA and the like.
  • the term "containing" in the food or feed of the present invention means inclusion, addition and / or dilution.
  • “containing” means that the active ingredient used in the present invention is contained in food or feed
  • additional means that the active ingredient used in the present invention is added to the raw material of food or feed.
  • “dilution” refers to a mode in which a raw material for food or feed is added to the active ingredient used in the present invention.
  • the method for producing the food or feed of the present invention is not particularly limited.
  • compounding, cooking, cooking, etc. can be produced by their production method according to general foods or feeds, and the resulting foods or feeds can have anti-foaming action of cells and Z or It would be good if the active ingredient according to the present invention having ACAT inhibitory action was contained!
  • the food of the present invention is not particularly limited.
  • a processed cereal product processed flour product, processed starch product, premixed caloche product, rice cake, etc.
  • a processed cereal product containing the active ingredient according to the present invention.
  • Macaro- Bread, Anzu, Buckwheat, Rice cake, Rice noodles, Harusame, Packaging rice cake, etc.
  • Oil and fat processed products Oil and fat processed products (Plastic oil, Tempura oil, Salad oil, Mayonnaise, Dressing, etc.), Processed soybean products (Tofu , Bean paste, natto, etc.), processed meat products (ham, bacon, pressed ham, sausage, etc.), marine products (frozen groundnut, power boiled rice cake, chikuwa, hanpen, fried fish, tsumire, streaks, fish ham, sausage Bonito, dried bonito, processed fish eggs, canned fish, boiled tsukudani, etc.), dairy products (raw milk, cream, yogurt, butter, cheese, con
  • the active ingredient is contained alone or in plural, added and Z or diluted, and the content thereof exhibits an anti-foaming action of cells and a Z or ACAT inhibitory action.
  • the shape is not particularly limited, and includes powders, tablets, granules, capsules and the like that can be taken orally.
  • the food of the present invention includes a processed product of button bow as it is or mixed appropriately with an appropriate emulsifier or excipient. These foods can be eaten as drinks as they are or mixed with water.
  • the active ingredient of the present invention is mixed with the juice of a plant other than the plant used in the present invention (vegetables, fruits, etc.) or simultaneously with the plant used in the present invention. It can be squeezed into a health drink.
  • the juices of various plants used in the present invention are diluted with water, or assipida, parsley, celery, licorice, carrot, komatsuna, turnip, tomato, tangerine, lemon, grapefruit, kiwi, spinach, radish.
  • the content of the active ingredient in the food of the present invention is not particularly limited, and can be selected as appropriate in terms of its functionality and activity expression.
  • the content is preferably 0.1% by weight or more, more preferably 0.5 to 95% by weight, and further preferably 1 to 90% by weight.
  • the active ingredient contained therein is preferably 0.1 ⁇ g to 10 gZkg body weight per day for an adult.
  • the active ingredient is 3, -acetooxy-4, mono-senesioxyloxy 3,4, -dihydroceserin, its derivatives and Z or pharmaceutically
  • adults should preferably take 0.1 ⁇ g to 5 gZkg body weight, more preferably 1 ⁇ g to 2 gZkg body weight, more preferably 10 g to lgZkg body weight per day.
  • the present invention provides a biological feed having an anti-foaming action of cells and an action of inhibiting Z or ACAT, comprising the above-mentioned active ingredient, that is, containing, adding and Z or diluting. Furthermore, as another aspect, there is also provided a method for breeding an organism characterized by administering the active ingredient to the organism. Moreover, as another aspect of the present invention, there is provided a biological breeding agent comprising the above-mentioned active ingredient.
  • the organism is not limited, and examples thereof include farm animals and pet animals.
  • farm animals and pet animals As farmed animals, livestock such as horses, rushes, pigs, hidges, goats, ratadas, llamas, laboratory animals such as mice, rats, guinea pigs, magpies, etc. Examples include crustaceans or shellfish.
  • pet animals include Inu and cats.
  • feed include feed for maintenance and Z or improvement.
  • biological breeding agents include soaking agents, feed additives, and beverage additives.
  • the present invention is based on the antifoaming action and Z or ACAT inhibitory action of the cells of the active ingredient used in the present invention in the above-described organisms to which they are applied. It is expected that the same effects as those of the therapeutic agent or preventive agent will be exhibited. That is, the feed of the present invention is caused by a disease that requires an antifoaming action of cells and a Z or ACAT inhibitory action for treatment or prevention in the organism, such as arteriosclerosis and hyperlipidemia, which are caused by these factors. It can exert a therapeutic or preventive effect on the disease.
  • the active ingredient used in the present invention is usually, for example, when the processed product of the present invention is used as an active ingredient, the active ingredient contained therein is preferably 0.1 ⁇ g to 10 g Zkg per day of the target organism.
  • Body weight more preferably 1 ⁇ g to 5 gZkg body weight, still more preferably 10 g to 2 gZkg body weight, and 3′-acetoxy-4 ′ senecioyloxy-3 ′, 4′-dihydroserine as an active ingredient
  • the target organism is preferably 0.1 ⁇ g to 5 g Zkg body weight, more preferably per day.
  • the administration is performed, for example, by adding and mixing the active ingredient in the raw material of the artificially mixed feed to be provided to the target organism, or by mixing it with the powdered raw material of the artificially mixed feed and further adding and mixing it with the other raw materials. be able to.
  • the content of the active ingredient in the feed is not particularly limited, and may be set as appropriate according to the purpose. For example, when the processed product of the present invention is used as an active ingredient, it is preferably 0 in the feed. 1% by weight or more, preferably 0.5 to 95% by weight, more preferably 1 to 90% by weight.
  • the method for producing the feed of the present invention is not particularly limited, and if the formulation is similar to that of a general feed, the presently produced feed has a cell antifoaming action and a sputum or ACAT inhibitory action. It suffices if the active ingredient according to the invention is included.
  • a biological rearing agent can be prepared in the same manner.
  • a feed comprising the active ingredient used in the present invention having an antifoaming effect on cells and a wrinkle or ACAT inhibitory effect, or a cell anti-foaming effect is used.
  • a liquid containing the active ingredient used in the present invention having a foaming action for example, a solution obtained by dissolving the immersion agent in water
  • livestock, laboratory animals, poultry, pets It is possible to maintain or improve the physical condition of animals and the like.
  • these aspects are one aspect
  • the present invention also includes a method for treating or preventing a disease requiring an anti-foaming action of cells and an anther or ACAT inhibitory action for treatment or prevention, comprising administering the active ingredient to a subject.
  • a method for treating or preventing a disease requiring an anti-foaming action of cells and an anther or ACAT inhibitory action for treatment or prevention comprising administering the active ingredient to a subject.
  • I will provide a.
  • the subject is preferably a human being who requires a cell antifoaming action and a Z or ACAT inhibitory action, such as a cultured animal or a pet animal as described above. Good.
  • the effective amount means that when the active ingredient is administered to the subject, the antifoaming action of the cells compared to the subject not administered the active ingredient. And the amount of the component exhibiting Z or ACAT inhibitory action.
  • the specific effective amount is appropriately set according to the administration form, administration method, purpose of use and age, weight, symptom, etc. of the subject.
  • the active ingredient contained therein is preferably 0.1 ⁇ g to 10 gZkg body weight, more preferably 1 ⁇ g to 5 gZkg body weight, more preferably human (eg, adult) per day. 10g ⁇ 2gZkg body weight and using 3, -acetoxy-4, -seneci oiloxy-3 ', 4'-dinoidoidoserine, its derivatives and / or pharmaceutically acceptable salts as active ingredients
  • human for example, an adult
  • human is preferably administered at a dose of 0.1 ⁇ g to 5 g Zkg body weight, more preferably 1 ⁇ g to 2 g Zkg body weight, still more preferably g to LgZkg body weight per day.
  • an effective amount of the active ingredient is added to the method for treating or preventing a disease requiring an antifoaming action and Z or ACAT inhibitory action of cells. It may be administered to the subject as it is, or may be administered as a pharmaceutical, food, or feed as described above. Further, there is no limitation on the administration method. For example, it may be administered by oral administration, injection or the like, as in the case of the above-mentioned medicine.
  • the target disease of the medicament, food or feed of the present invention can be treated or prevented, for example, arteriosclerosis or hyperlipidemia, An effect of treating or preventing a disease caused by these as causative factors can be exhibited.
  • the active ingredient used in the present invention does not show toxicity even if the living body is administered in an effective amount for expression of the action.
  • the active ingredient used in the present invention does not show toxicity even if the living body is administered in an effective amount for expression of the action.
  • the active ingredient used in the present invention does not show toxicity even if the living body is administered in an effective amount for expression of the action.
  • a single dose of buttonbofu ethanol extract, 3, -acetoxy-4, -senesioyloxy-3,4, -dihydroceserin at lgZkg body weight is given to mice, unacceptable.
  • no mortality was observed even if the lgZkg body weight was administered orally once.
  • Macrophages take denatured LDL (such as acetyl LDL (Ac-LDL)) into cells and synthesize cholesterol esters into foam. The anti-foaming activity of macrophages by each test sample was measured.
  • LDL such as acetyl LDL (Ac-LDL)
  • RAW264 Containing RAW264. 7 cells (ATCC TIB 71) at 4 x 10 5 cells / ml in Dulbecco's modified Eagle's medium (Sigma, D5796), containing 10% urine fetal serum (Camprex) After turbidity, 1 mL was added to each well of a 24-well microtiter plate and cultured at 37 ° C in the presence of 5% carbon dioxide. Next, replace with UltraCHO medium (Camprex B2 724), and each well has a concentration of dimethyl sulfoxide solution 2 / z L of each test sample prepared in the above preparation example as shown in Table 1 below. Was added as follows.
  • the amount of total cholesterol in the cell and the amount of free cholesterol were measured, and the amount of cholesterol ester was calculated.
  • the total cholesterol content in 10 ⁇ L of the solution is measured using the Cholesterol® test (manufactured by Wako Pure Chemical Industries, Ltd., 439-17501) and the amount of free cholesterol is determined. It was measured using a free cholesterol test (Wako Pure Chemical Industries, 435-35801). All measurements were performed in duplicate. Total cholesterol ester biosynthesis Cholesterol capacity was determined by subtracting the amount of free cholesterol. The antifoaming activity was calculated by the following formula.
  • Anti-foaming activity (%) 100- ((Cholesterol ester biosynthesis amount when test sample is added) 1 (Cholesterol ester biosynthesis amount in the case where Ac— LDL is not added)) ⁇ ((Cholesterol ester biosynthesis amount when dimethyl sulfoxide is added) 1 (Cholesterol ester biosynthesis amount in the category without Ac— LDL addition)) X 100
  • Table 1 shows the inhibitory activity against cholesterol ester accumulated in the Macphage phage at each final concentration of each test sample, and each sample listed in the table shows significant antifoam activity. It was.
  • Spmgue—4 Dawley rats were raised for 1 week and sacrificed.
  • the liver was immediately removed, washed gently with cold saline, and then sucrose buffer (0.3 M sucrose, 50 mM Tris HC1, 1 mM EDTA, 50 mM NaCl, pH 7. Immersion (25mLZl) in 4).
  • sucrose buffer 0.3 M sucrose, 50 mM Tris HC1, 1 mM EDTA, 50 mM NaCl, pH 7. Immersion (25mLZl) in 4
  • the obtained liver was homogenized, and the operation of removing the precipitate by centrifuging at 10,000 ⁇ g for 30 minutes was repeated twice.
  • the obtained supernatant was centrifuged at 105,000 xg for 70 minutes to collect the precipitate, and suspended in an appropriate amount of lOOmM phosphate buffer (pH 7.4). Protein concentration to 10mg / ml
  • the suspension was suspended again in a phosphate buffer, and after adding ED
  • ACAT enzyme activity of ACAT was measured with some improvement according to the method of Lee et al. (Planta Med., 2004, 70, 678-679).
  • a group in which only a dimethyl sulfoxide solution was added without adding a compound and a group in which a compound FR179254 (final concentration M, manufactured by Merck & Co., 344235) known to have ACAT inhibitory activity was added as a positive control.
  • a compound FR179254 final concentration M, manufactured by Merck & Co., 344235
  • ACAT inhibitory activity was added as a positive control.
  • the radioactivity was measured with a liquid scintillation counter LS6500 (manufactured by Beckman) using Ultima Gold (Perkin Elma Life Science Co., 6013329) as a scintillation cocktail.
  • Each reaction was performed in duplicate.
  • the ACAT inhibitory activity (%) of each test sample was calculated by using the following formula as the inhibition rate when 10 ⁇ of FR179254 as a positive control was added to 100%.
  • Inhibitory activity (%) (([Radioactivity of control category (cpm)] [Radioactivity of test sample addition category (cpm)]) / ([Radioactivity of control category (cpm)] — [10 M FR179254 Caro Category radioactivity (cpm)])) X 100
  • Table 2 shows AC at each final concentration of each test sample.
  • a processed product derived from button bow fu, 3'-acetoxy 4 'senecioyloxy-3', 4'-dihydroserine, a derivative thereof and / or a pharmaceutically acceptable salt thereof is contained.
  • a medicament, food, or feed for treating or preventing a disease that requires anti-foaming action of cells and Z or ACAT inhibitory action for treatment or prevention.
  • the medicament is useful as a therapeutic or prophylactic agent for arteriosclerosis, hyperlipidemia, and diseases caused by these factors.
  • the food containing the active ingredient of the present invention is a functional food useful for maintaining the homeostasis of the living body by the antifoaming action of the cells and the Z or ACAT inhibitory action.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Vascular Medicine (AREA)
  • Polymers & Plastics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Fodder In General (AREA)

Abstract

La présente invention concerne un agent thérapeutique ou agent préventif pour une maladie nécessitant une action anti-mousse et/ou une action inhibitrice de l'acyl-CoA-cholestérol acyl transférase sur une cellule en traitement ou prévention, caractérisé en ce qu'il comprend, en tant qu'ingrédient actif, une matière transformée dérivée de Peucedanum japonicum Thunb.
PCT/JP2006/301200 2005-02-04 2006-01-26 Agent therapeutique WO2006082743A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2007501541A JPWO2006082743A1 (ja) 2005-02-04 2006-01-26 治療剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005-029596 2005-02-04
JP2005029596 2005-02-04

Publications (1)

Publication Number Publication Date
WO2006082743A1 true WO2006082743A1 (fr) 2006-08-10

Family

ID=36777131

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/301200 WO2006082743A1 (fr) 2005-02-04 2006-01-26 Agent therapeutique

Country Status (5)

Country Link
JP (1) JPWO2006082743A1 (fr)
KR (1) KR20070100829A (fr)
CN (1) CN101115491A (fr)
TW (1) TW200638942A (fr)
WO (1) WO2006082743A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008015950A1 (fr) * 2006-08-02 2008-02-07 Takara Bio Inc. Inhibiteur d'acat
WO2009054504A1 (fr) * 2007-10-24 2009-04-30 Suntory Holdings Limited Agent ligand pour un récepteur activé par les proliférateurs de peroxysomes (ppar)
JP2011184356A (ja) * 2010-03-09 2011-09-22 Shiseido Co Ltd 経口摂取用毛穴縮小剤
WO2012111643A1 (fr) * 2011-02-14 2012-08-23 株式会社アミノアップ化学 Promoteur de production d'adiponectine, et composition médicinale, aliment, boisson et aliment pour animaux contenant un promoteur de production d'adiponectine
JP7444375B2 (ja) 2019-12-28 2024-03-06 株式会社 沖縄リサーチセンター 下部尿路症状改善用組成物

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5666053B1 (ja) * 2014-08-01 2015-02-12 株式会社 資生堂 長寿遺伝子発現増強剤

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60260520A (ja) * 1984-06-07 1985-12-23 Takagi Koichi 医薬組成物
JPS60260515A (ja) * 1984-06-07 1985-12-23 Takagi Koichi セセリン化合物を有効成分とする医薬組成物
WO2004096198A1 (fr) * 2003-05-02 2004-11-11 Takara Bio Inc. Agent therapeutique
WO2005074906A1 (fr) * 2004-02-06 2005-08-18 Takara Bio Inc. Remede

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60260520A (ja) * 1984-06-07 1985-12-23 Takagi Koichi 医薬組成物
JPS60260515A (ja) * 1984-06-07 1985-12-23 Takagi Koichi セセリン化合物を有効成分とする医薬組成物
WO2004096198A1 (fr) * 2003-05-02 2004-11-11 Takara Bio Inc. Agent therapeutique
WO2005074906A1 (fr) * 2004-02-06 2005-08-18 Takara Bio Inc. Remede

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEN I.-S.: "Coumarins and antiplatelet aggregation constituents from Formosan Peucedanum japonicum", PHYTOCHEMISTRY, vol. 41, no. 2, 1996, pages 525 - 530, XP002997573 *
DATABASE JICST-EPLUS [online] UEZU E. ET AL.: "Effects of Morus australis, Crepidiastrum lanceolatum, Peucedanum japonicum, Carica papaya, Benincasa cerifera, Abelmoschus esculentus and Artemisia princeps on plasma cholesterol levels in mice fed goat-soup dish extracts", Database accession no. (990781350) *
IGAKU TO SEIBUTSUGAKU (MEDICINE AND BIOLOGY), vol. 138, no. 6, 1999, pages 175 - 178, XP002997572 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008015950A1 (fr) * 2006-08-02 2008-02-07 Takara Bio Inc. Inhibiteur d'acat
WO2009054504A1 (fr) * 2007-10-24 2009-04-30 Suntory Holdings Limited Agent ligand pour un récepteur activé par les proliférateurs de peroxysomes (ppar)
JP2011184356A (ja) * 2010-03-09 2011-09-22 Shiseido Co Ltd 経口摂取用毛穴縮小剤
WO2012111643A1 (fr) * 2011-02-14 2012-08-23 株式会社アミノアップ化学 Promoteur de production d'adiponectine, et composition médicinale, aliment, boisson et aliment pour animaux contenant un promoteur de production d'adiponectine
JPWO2012111643A1 (ja) * 2011-02-14 2014-07-07 株式会社アミノアップ化学 アディポネクチン産生促進剤、並びにアディポネクチン産生促進剤を含む医薬組成物、飲食品、及び飼料
JP7444375B2 (ja) 2019-12-28 2024-03-06 株式会社 沖縄リサーチセンター 下部尿路症状改善用組成物

Also Published As

Publication number Publication date
TW200638942A (en) 2006-11-16
CN101115491A (zh) 2008-01-30
KR20070100829A (ko) 2007-10-11
JPWO2006082743A1 (ja) 2008-06-26

Similar Documents

Publication Publication Date Title
WO2013099982A1 (fr) Agent de prévention de l'atrophie musculaire
WO2006082743A1 (fr) Agent therapeutique
JPWO2004100969A1 (ja) 治療剤
KR100883992B1 (ko) 초피 추출물 또는 이로부터 분리한 화합물을 포함하는심장순환계 질환의 예방 및 치료용 조성물
JP6021166B2 (ja) 血圧降下剤
JP6042800B2 (ja) トマトシドａの抽出方法
JP5175442B2 (ja) ヤーコン由来の抗ガン剤
JPWO2004112817A1 (ja) セリ科植物由来抽出物およびその製造方法
JP5619752B2 (ja) パンドラチン誘導体またはボエセンベルギアパンドラタ抽出物の新規な用途
WO2008015950A1 (fr) Inhibiteur d'acat
JP4537024B2 (ja) 炎症疾患予防・治療剤
JP4224593B2 (ja) ワサビを有効成分とする脂肪蓄積抑制用組成物
US20090292012A1 (en) Therapeutic Agent
JP4751066B2 (ja) 治療剤
KR102428082B1 (ko) 항염증 면역활성 및 항산화 활성을 가지며, 노인의 근력 또는 근육 강화를 위한 근세포 조성에 우수한 효과를 제공하는 프테로카리아 스테놉테라 추출물을 포함하는 화장료 조성물, 약학적 조성물, 및 식품 조성물
JP3710854B2 (ja) 水易溶性ヤマモモ科植物抽出物
JPWO2014103410A1 (ja) Ｉｇｆ−１産生促進剤
KR20110122961A (ko) 헴프 종자 추출물을 포함하는 관절염 예방 및 치료용 조성물
WO2022138258A1 (fr) Inhibiteur de pde5
JP2009167153A (ja) 血糖値上昇抑制剤
JP2011121919A (ja) 脂質吸収抑制剤
JP2007284366A (ja) 脂質吸収阻害剤およびその摂取方法
JP2023109364A (ja) ミソハギ含有組成物
JP2022046069A (ja) 筋萎縮抑制剤
KR20160084990A (ko) 아까시나무 추출물을 함유하는 동맥경화증, 심근경색, 뇌졸중, 혈관성치매, 간질환, 이상지질혈증 또는 혈전증 예방 또는 치료용 조성물

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2007501541

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 200680003989.5

Country of ref document: CN

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 1020077019930

Country of ref document: KR

122 Ep: pct application non-entry in european phase

Ref document number: 06712382

Country of ref document: EP

Kind code of ref document: A1

WWW Wipo information: withdrawn in national office

Ref document number: 6712382

Country of ref document: EP