WO2007040006A1 - Activateur pour un recepteur actionne par un proliferateur de peroxysome (pparg) et composition contenant l'activateur, destines a la prevention ou a l'amelioration d'un symptome predetermine - Google Patents
Activateur pour un recepteur actionne par un proliferateur de peroxysome (pparg) et composition contenant l'activateur, destines a la prevention ou a l'amelioration d'un symptome predetermine Download PDFInfo
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- WO2007040006A1 WO2007040006A1 PCT/JP2006/317485 JP2006317485W WO2007040006A1 WO 2007040006 A1 WO2007040006 A1 WO 2007040006A1 JP 2006317485 W JP2006317485 W JP 2006317485W WO 2007040006 A1 WO2007040006 A1 WO 2007040006A1
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- WIPO (PCT)
- Prior art keywords
- acid
- peroxisome proliferator
- activator
- disease
- responsive receptor
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Classifications
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
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- 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
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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Definitions
- Peroxisome proliferator-responsive receptor PPAR / activator and a composition for preventing or ameliorating specific symptoms containing the activator
- the present invention relates to a peroxisome proliferator-responsive receptor ⁇ activator and a composition for preventing or ameliorating a specific symptom comprising the active agent. More specifically, it acts as a peroxisome proliferator-activated receptor gamma activator and is selected from the group consisting of insulin resistance, type 2 diabetes, hyperlipidemia, hypertension, visceral fat obesity and fatty liver
- the present invention relates to a composition having an action of preventing or ameliorating at least one kind of symptom.
- Peroxisome proliferator-activated receptor is an activator-dependent transcriptional regulator belonging to the nuclear receptor family that controls the expression of genes involved in lipid and sugar metabolizing sugars. .
- PPAR-a is mainly expressed in adipose tissue, immune cells, adrenal gland, spleen, and small intestine
- PPAR-a is expressed mainly in adipose tissue, liver, kidney, and skeletal muscle
- PPAR- ⁇ is mainly observed in tissue specificity. It is known that it is universally expressed and is known!
- PPAR- ⁇ is involved in adipocyte differentiation, and this activator (agonist) promotes adipocyte differentiation and actively takes up blood glucose. Increases the number of fat cells to lower blood sugar level, hypersensitivity to insulin insensitivity, suppresses hyperplasia of fat cells, increases insulin sensitivity! Increases sensitive small fat cells to lower blood sugar level It is known to decrease, increase adiponectin production, decrease blood lipids (particularly triglycerides), and control the function of vascular constituent cells (Non-Patent Documents 2, 3, 4, 5). 6).
- PPAR- ⁇ activator is useful for reducing visceral fat, suppressing accumulation of visceral fat, improving lipid metabolism abnormality, improving glucose metabolism abnormality, insulin resistance, type 2 diabetes, hyperlipidemia, hypertension It is effective as an agent for preventing and improving or reducing visceral fat obesity, fatty liver and the like.
- PPAR- ⁇ activator has conjugated triene structure or tetrane structure in the molecule.
- Unsaturated fatty acids having 10 to 26 carbon atoms Patent Document 1
- a unsaturated fatty acids such as linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, 9-hydroxyoctadecadienoic acid 13-hydroxyoctadedecadiene Hydroxy fatty acids such as acids, arachidonic acid metabolites such as 15 deoxy ⁇ 12 prostaglandin J2 and ⁇ 12 prostaglandin J2 (non-patent document 2), thiazolidine derivatives such as pioglitazone, troglitazone, and rosiglitazone (non-patent document) 4 and 7) are known.
- the thiazolidine derivative has an excellent insulin improving action and is clinically used as a therapeutic agent for type 2 diabetes.
- thiazolidine derivatives have problems that cause strong side effects such as liver damage and weight gain, and development of safer antidiabetic drugs is desired.
- Non-Patent Document 8 It is known that it is an abietic acid PPAR- ⁇ activator, which is a kind of succinic acid constituting rosin (see Non-Patent Document 8). However, the activity of abietic acid is not strong, and Non-Patent Document 8 does not teach or suggest any of the activity of succinic acid other than abietic acid.
- Patent Document 1 Japanese Unexamined Patent Publication No. 2000-355538
- Non-Patent Document 1 History of Medicine, 1998, 184 ⁇ , 519-523
- Non-Patent Document 2 Diabetology, 1999, 42 ⁇ , 1033-1049
- Non-Patent Document 3 Japanese Clinical, 2005, 63 ⁇ , 4, 539-548
- Non-Patent Document 4 Japanese Clinical Practice, 2005, 63 ⁇ , 4, 549-555
- Non-Patent Document 5 Japanese Clinical Practice, 2005, 63 ⁇ , No. 4, pp. 557-562
- Non-Patent Document 6 Japanese Clinical, 2005, 63 ⁇ , No. 4, pp. 631-642
- Non-Patent Document 7 Journal of Pharmaceutical Sciences, 2002, 122 (11), 909-918
- Non-Patent Document 8 F'B'B'S 'Letters, 2003, 550, 190-194 Disclosure of the Invention
- the present invention provides a useful peroxisome proliferator-responsive receptor ⁇ activator with high safety, and insulin resistance, type 2 diabetes, visceral fat obesity, fatty liver, hyperlipidemia
- the aim is to provide a thread and composition that has the effect of preventing or ameliorating hypertension, etc. Target.
- the present inventors paid attention to the succinic acid component contained in rosin, which is a natural product, and as a result of earnestly examining its relationship with activation of peroxisome proliferator-responsive receptor ⁇ , And at least one compound selected from the group consisting of dehydroabietic acid, 13
- the present inventors have found that it has an excellent peroxisome proliferator-responsive receptor ⁇ activation action, and further research based on this finding has led to the completion of the present invention.
- the present invention provides:
- Peroxisomes comprising at least one compound selected from the group consisting of dehydroabietic acid, 13 j8- ⁇ 8 -dihydroabietic acid and isopimaric acid or a pharmaceutically acceptable salt thereof as an active ingredient
- Proliferator-responsive receptor ⁇ activator
- peroxisome proliferator-activated receptor ⁇ The disease or symptom mediated by peroxisome proliferator-activated receptor ⁇ is insulin resistance, type 2 diabetes, hyperlipidemia, hypertension, visceral fat type obesity or fatty liver as described in (2) above Peroxisome proliferator-activated receptor ⁇ activator,
- the peroxisome proliferator-responsive receptor 0 activator according to (1) above which is a composition for preventing or improving insulin resistance, type 2 diabetes, hyperlipidemia, hypertension, visceral fat obesity or fatty liver ,
- Insulin resistance type 2 diabetes, hyperlipidemia, hypertension, visceral fat-type obesity or peroxisome proliferator-responsive receptor ⁇ activator according to (1)
- a composition for preventing or improving fatty liver A composition for preventing or improving fatty liver,
- composition for prevention or improvement according to the above (5) which is a food
- a peroxisome proliferator-responsive receptor comprising at least one compound selected from the group consisting of dehydroabietic acid, 13 j8- ⁇ 8 -dihydroabietic acid and isopimaric acid, or a pharmaceutically acceptable salt thereof a food characterized in that a disease or symptom mediated by ⁇ is prevented or improved
- peroxisome proliferator-responsive receptor ⁇ The disease or symptom mediated by peroxisome proliferator-responsive receptor ⁇ is insulin resistance, type 2 diabetes, hyperlipidemia, hypertension, visceral fat obesity or fatty liver as described in (8) above Food,
- Peruokishisomu proliferator-activated receptor ⁇ is dehydroabietic acid for the manufacture of a medicament for improvement of were prevention or a disease or condition mediated, 13 ⁇ - ⁇ 8 - than Jihidoroabi Echin acid and isopimaric acid strength becomes the group Use of at least one selected compound or a pharmaceutically acceptable salt thereof,
- Peruokishisomu proliferator-activated receptor ⁇ activator of the present invention Dehidoroabiechi phosphate, 13 j8- ⁇ 8 least one compound or a pharmaceutically selected from dihydroabietic acid and isopimaric acid force group consisting acceptable It contains a salt obtained as an active ingredient.
- dehydroabietic acid is generally called succinic acid, and is an amber transparent glass having a softening point of about 70 to 80 ° C obtained by refining pine resin produced from pine trees. It is a component of rosin. 13 j8- ⁇ 8 Dihydroabietic acid is a component of hydrogenated rosin obtained by hydrogenating rosin. Isopimaric acid is a component of rosin. These are all known as active ingredients of force peroxisome proliferator-activated receptor ⁇ activators, which are known compounds, respectively!
- the compound as the active ingredient can be easily isolated and purified or synthesized by a known method.
- a strong salt examples include all pharmacologically acceptable ones.
- a pharmacologically acceptable salt is preferably a less toxic salt.
- Suitable salts include, for example, salts of alkali metals (potassium, sodium, lithium, etc.), salts of alkaline earth metals (calcium, magnesium, etc.), ammonium salts (tetramethylammonium salt, tetraptylammonium salt).
- organic amines triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) methylamine, lysine, arginine, N -Methyl D glutamine etc.
- organic amines triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) methylamine, lysine, arginine, N -Methyl D glutamine etc.
- the PPAR y activating action (PPAR y agonist activity) of these active ingredients is measured by the method of, for example, EF I. B I. S Letters, 2002, 514 ⁇ , 315-322. it can. That is, a plasmid (pM—PPAR ⁇ ) that produces a chimeric protein of the ligand binding site of PPAR- ⁇ and the DNA binding site of GAL4 (yeast DNA-binding transcription factor activity factor), and the luciferase gene that is the reporter gene
- the plasmid (4 X UASg-luc) containing 4 GAL4 response elements (UA Sg) incorporated upstream is cotransfected into the cultured cells of African green monkey kidney (CV-1) by the lipofussion method.
- the obtained transformant is cultured for a certain period of time, and then contacted with the test compound to activate the PPAR ⁇ GAL4 chimeric protein and enhance the binding to UASg upstream of 4 X UASg-luc, thereby producing luciferase. increase.
- the PPAR ⁇ activity can be evaluated by measuring the activity of the produced luciferase.
- the protein at the ligand binding site of PPAR-y is a human PP AR- ⁇ amino acid conjugate [J (http://www.genome.jp/dbget-bin/www-bget? sp: PPAR—HUMA N)) corresponding to the amino acid sequence of 174 to 475%.
- the protein of the DNA binding site of GAL4 (yeast DNA-binding transcription factor activator) is the amino acid sequence of GAL4 (see http://www.genome.jp/dbget—bin/www_bget?sp:GAL4_YEAST) It corresponds to amino acid sequence 1-147.
- the active ingredient of the present invention is based on the PPAR ⁇ activity activity, and improves glucose metabolism, improves fat metabolism, lowers blood glucose, suppresses body fat accumulation, inhibits visceral fat accumulation,
- the active ingredient of the present invention has an action of reducing cytodynamic force (for example, MCP-1) which is an inflammatory factor related to obesity.
- Peruokishisomu proliferator-activated receptor ⁇ activator of the present invention the prevention of lifestyle-related diseases Ya metabolic syndrome associated with obesity, are useful as improvers, more specifically, I insulin resistance, 2 It is useful as a preventive / ameliorating agent for type 2 diabetes, hyperlipidemia, hypertension, visceral fat obesity and fatty liver.
- peroxisome proliferator-responsive receptor ⁇ activator of the present invention and a composition containing the peroxisome proliferator-responsive receptor ⁇ activator (hereinafter, both are also referred to as a preparation) are used as pharmaceuticals, oral agents and injections together with conventional carriers are used. Suppositories, external preparations, suppositories or inhalants. Examples of oral preparations include dosage forms such as tablets, granules, fine granules, powders, capsules, solutions, emulsions, suspensions, and syrups. These preparations can be produced by a method known per se.
- the active ingredient of the present invention and pharmaceutically acceptable additives such as excipients (eg lactose, starch, sucrose, glucose, Mantle, starch, inorganic salts, etc.), lubricants (eg talc, waxes, hydrogenated vegetable oils, sucrose fatty acid esters, magnesium stearate, calcium stearate, aluminum stearate, etc.), disintegrants ( Examples: carmellose, carmellose calcium, starch, crystalline cellulose, low-substituted hydroxypropyl cellulose, etc.), binders (eg starch, dextrin, gum arabic powder, hydroxypropyl starch, crystalline cellulose, ethyl cellulose, methylcellulose, Sodium carboxymethyl cellulose, hydroxypropyl cellulose, polybule Mix by known methods, etc.) together with such pyrrolidone, granulation, can be produced by excipients (eg lactose, starch, sucrose, glucose, Mantle,
- suitable coating agents eg, gelatin, sucrose, gum arabic, carnapa wax, etc.
- enteric coating agents eg, cellulose acetate phthalate, methacrylic acid copolymer, hydroxypropyl cellulose phthalate
- Carboxymethylethyl cellulose, etc. e.g., cellulose acetate phthalate, methacrylic acid copolymer, hydroxypropyl cellulose phthalate
- the active ingredient of the present invention is uniformly mixed with known excipients, or granulated or granulated, and if necessary, a more suitable coating agent.
- excipients include, for example, magnesium stearate, calcium stearate, talc or light anhydrous key acid to improve fluidity and lubricity, crystalline cellulose and lactose for pressurized fluidity, or the above disintegration Agents and the like.
- a stabilizer eg, sodium edetate
- a suspending agent eg, gum arabic, carmellose, etc.
- a flavoring agent eg, simple substance
- Syrup e.g., glucose, etc.
- fragrance e.g., purified water, butanol, vegetable oil, emulsifier and the like
- purified water butanol, vegetable oil, emulsifier and the like
- the injection may be an aqueous injection or an oily injection!
- an aqueous solvent eg, distilled water for injection, physiological saline, aqueous glucose solution, etc.
- a pharmaceutically acceptable additive eg, an isotonic agent (eg, Sodium chloride, potassium chloride, glycerin, mannitol, sorbitol, glucose, propylene glycol, etc.), buffer (eg phosphate buffer, acetate buffer, carbonate buffer, citrate buffer, Tris buffer, glutamate buffer, epsilon aminocaproate buffer, etc.), preservative (eg, chlorobutanol, etc.), thickener (eg, hydroxyethyl cellulose, hydroxypropyl cellulose, polybutanol, polyethylene glycol) Etc.), stabilizers (eg, sodium hydrogen sulfite, sodium thiosul
- an isotonic agent eg, Sodium chloride, potassium chloride,
- solubilizers such as alcohols (ethanol, etc.), polyalcohols (propylene glycol, polyethylene glycol, etc.), nonionic surfactants (polysorbate 80, polyoxyethylene hydrogenated castor oil 50, etc.) can be used.
- the oily solvent examples include sesame oil, peanut oil, and soybean oil. Corn oil or the like may be used, and benzyl benzoate, benzyl alcohol or the like may be used as a solubilizing agent.
- the prepared injection solution is usually filled in an appropriate ampoule or vial.
- the concentration of the active ingredient of the present invention in the injection is usually adjusted to about 0.001 to 10. OwZv%, preferably about 0.005 to OwZv%.
- Examples of the external preparation include ointments, creams, lotions, and the like.
- ointments and talums for example, water-absorbing ointments, hydrophilic ointments, simple ointments, white ointments or macrogols.
- the lotion may contain commonly used additives.
- additives include suspending agents, emulsifiers, wetting agents (for example, glycerin, propylene glycol, sorbitol, 1, 3-butylene glycol, dl-pyrrolidone carboxylic acid, sodium lactate, etc.) or preservatives (for example, noraoxybenzoates, salt benzalkonium, chlorobutanol, benzyl alcohol, sodium dehydroacetate, sodium edetate, Boric acid, borax, etc.).
- suspending agents for example, glycerin, propylene glycol, sorbitol, 1, 3-butylene glycol, dl-pyrrolidone carboxylic acid, sodium lactate, etc.
- preservatives for example, noraoxybenzoates, salt benzalkonium, chlorobutanol, benzyl alcohol, sodium dehydroacetate, sodium edetate, Boric acid, borax, etc.
- Suppositories can also be prepared by a conventional formulation method using conventional bases (for example, cacao butter, laurin butter, glyce gelatin, macrogol, witepsol, etc.).
- bases for example, cacao butter, laurin butter, glyce gelatin, macrogol, witepsol, etc.
- Inhalants can also be adjusted by conventional means in the preparation.
- the additive may be any additive generally used in inhalable preparations.
- the above-mentioned excipients, binding Agents, lubricants, preservatives, stabilizers, tonicity agents, pH adjusting agents or flavoring agents taenoic acid, menthol, glycyrrhizin ammonium salt, glycine, fragrance, etc.
- a propellant a liquefied gas propellant, a compressed gas, or the like is used.
- the liquefied gas propellant examples include fluorinated hydrocarbons (alternative fluorocarbons such as HCFC22, HCFC-123, HCFC-134a, and HCFC142), liquefied petroleum, dimethyl ether, and the like.
- the compressed gas examples include soluble gases (such as carbon dioxide and nitrous acid) and insoluble gases (such as nitrogen).
- the preparation of the present invention is used as a food
- it is an additive acceptable as a food additive (eg, glucose, fructose, sucrose, maltose, sorbitol, stepioside, rubusoside, corn syrup, lactose, quenate, tartaric acid.
- a food additive eg, glucose, fructose, sucrose, maltose, sorbitol, stepioside, rubusoside, corn syrup, lactose, quenate, tartaric acid.
- Ri may be tablets, granules, capsules and the like.
- the preparation of the present invention can also be mixed with other food ingredients to make a food.
- other food ingredients are not particularly limited and can be used for various foods.
- foods that can be used include soy sauce, powdered soy sauce, miso, powdered miso, moromi, horsetail, fried potatoes, mayonnaise, dressing, vinegar, three cups of vinegar, powdered sushi vinegar, tentsuyu, katsuyu, sauce, ketchup, Yakiniku sauce, curry roux, Chinese element, stew element, soup element, dashi element, compound seasoning, mirin, new mirin, table sugar or coffee sugar, etc.
- Fertilizer cocoon, manju, uirou, ann, mutton, water mutton, brocade, jelly, castella, candy, etc. , Candy, caramel, candy or gummy jelly, ice cream, eye Candy or sherbet ice confectionery, ice honey syrup, butter cream, force Stard cream, flower paste, peanut paste or fruit paste spreads and pastes, jam, marmalade, syrup pickled or confectionery processed fruits and vegetables Cereal processed foods such as bread, rice bran, cooked rice or artificial meat, oil and fat foods such as salad oil or margarine, Fukujinzuke, lettuce pickles, Senzuke pickles Pickles, pickled vegetables such as takuan pickles or Chinese cabbage pickles, livestock meat products such as ham or sausage, fish meat ham, fish sausages, fish products such as scallops, chiku mushrooms or hampen, uni-salted squid, squid Delicacy such as salted spices, vinegared combs, dried sardines or dried puffer
- Soup, stew, oden, Happo vegetables, boiled beans, yakitori, steamed rice bowl or field Retort food such as boiled water, egg, milk drinks, egg products such as notter or cheese and dairy products, bottling and canning of fish meat, livestock meat, fruits or vegetables, synthetic liquor, brewed liquor, fruit liquor or Western liquor Alcohol, coffee, cocoa, juice, tea, tea, oolong tea, mineral beverages, carbonated beverages, soft drinks such as lactic acid beverages or lactic acid bacteria drinks, pudding mixes, hot cake mixes, instant juices, instant juices or instant soups Foods etc. are mentioned.
- the content of the preparation of the present invention in the food varies depending on the type of food, but the content of the active ingredient is usually about 0.001 to 0.1% by mass.
- CV-1 cells (cultured cells derived from male African green monkey kidney) were seeded in a 96-well culture plate at 6 X 10 3 per well, and cultured for 24 hours at 37 ° C and 5% CO.
- the medium includes 10% FBS (Ushi Fetal Serum), lOmlZL penicillin 'streptomycin solution (5000 IU / ml, 5000 ⁇ g / ml, GIBCO, respectively), 37 mg / L ascorbic acid (Wako Pure Chemical Industries, Ltd.) DMEM (Dulbeccos Modified Eagle Medium: manufactured by GIBCO) was used. After washing the cells with OPTI-MEM (GIBCO), p M -PPAR ⁇ and 4 X UASg -luc using Lipofectamine 'Plus (GIBCO) Transfusion.
- FBS Un Fetal Serum
- lOmlZL penicillin 'streptomycin solution 5000 IU / ml, 5000 ⁇ g / ml, GIBCO, respectively
- 37 mg / L ascorbic acid Wako Pure Chemical Industries, Ltd.
- DMEM Dulbeccos Modified Eagle Medium: manufactured by GIBCO
- PM-PPARy is a mammalian expression plasmid pM (Clontech), yeast-derived transcription factor GAL4 gene (amino acid sequence 1-147) and human PP AR- ⁇ ligand binding site gene (amino acid sequence 174-475).
- test compound was dissolved in dimethyl sulfoxide (DMSO), DMSO was used as an untreated control, and 1/1000 amount was added to the medium. After washing the cells with Ca- and Mg-containing phosphate buffered saline (PB S +), add Looklite (Packard) and use TopCount 'Microplate Scintillation Z Luminescence Counter (Packard). The luminescence intensity of luciferase was measured.
- DMSO dimethyl sulfoxide
- the control group was measured using pM instead of pM-PPAR y.
- calculate the ratio of the average value (n 4) of the luminescence intensity of the measurement group and the control group (measurement group Z control group), and determine the specific activity relative to the untreated control as the PPAR- ⁇ activity of the test compound. It was considered as a ⁇ action.
- Table 1 The results are shown in Table 1.
- dehydroabietic acid administration group significantly suppressed the increase in blood glucose level as compared to the control group, and the concentration of lebutin, insulin, MCP-1 and the amount of intraperitoneal fat Z body weight significantly decreased. I understand. From this result, it is clear that dehydroabietic acid has an effect of improving the metabolism of sugar and fat, an action of suppressing visceral fat accumulation, and an action of improving hyperinsulinemia.
- RAW264.7 cells were suspended in the DMEM medium described in Example 1, and the suspension (lX10 6 cellsZml) was dispensed into a 12-well culture plate at a rate of 2000 / zl per well in a 37 ° C CO incubator. After 2 hours of incubation, lipopolysaccharide (LPS, lOOng / mU Sigma)
- Magnesium stearate 0.4 g Add each of the above ingredients and mix well to make tablets for tableting according to the wet tablet preparation method. Add magnesium stearate and tablet, making 400 tablets. Tablets may be sugar-coated as necessary.
- the syrup 300g sugar 650g were melted in the 0.99 ° C, after cooling to 120 ° C, the Kuen acid 10g after was Karoe, 13
- the peroxisome proliferator-responsive receptor ⁇ activator according to the present invention suppresses or prevents insulin resistance, type 2 diabetes, visceral fat obesity, fatty liver, etc., hyperlipidemia, hypertension, etc. Can be used.
Abstract
Activateur pour un récepteur actionné par un proliférateur de péroxysome ? caractérisé en ce qu'il contient au moins un composé sélectionné dans le groupe constitué d'acide déshydroabiétique, d'acide 13ß-?8-dihydroabiétique et d'acide isopimarique ainsi que de leur sel pharmaceutiquement acceptable. L'actionneur est utile dans la prévention ou l'amélioration d'au moins un symptôme sélectionné dans le groupe comprenant la résistance à l'insuline, le diabète type 2, l'hyperlipémie, l'hypertension, l'obésité de type de graisse viscérale et la stéatose hépatique.
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPWO2007040005A1 (ja) * | 2005-09-06 | 2009-04-16 | 国立大学法人京都大学 | ペルオキシソーム増殖剤応答性受容体PPARα活性化剤、および該活性化剤を含有する特定症状の予防または改善用組成物 |
WO2009054504A1 (fr) * | 2007-10-24 | 2009-04-30 | Suntory Holdings Limited | Agent ligand pour un récepteur activé par les proliférateurs de peroxysomes (ppar) |
JP2011057556A (ja) * | 2009-09-04 | 2011-03-24 | Iwate Univ | 新規なCa2+シグナル伝達阻害剤 |
JP2014221734A (ja) * | 2013-05-13 | 2014-11-27 | 株式会社エヌ・エル・エー | ジンゲロール類を有効成分として含有する肝細胞活性化剤、並びに該肝細胞活性化剤を含有する固形製剤、液状製剤及び機能性食品 |
WO2018212362A1 (fr) * | 2017-05-19 | 2018-11-22 | 株式会社ヤマノビューティケミカル | Agent pour empêcher la dégradation et l'absorption des hydrates de carbone |
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JPWO2007040005A1 (ja) * | 2005-09-06 | 2009-04-16 | 国立大学法人京都大学 | ペルオキシソーム増殖剤応答性受容体PPARα活性化剤、および該活性化剤を含有する特定症状の予防または改善用組成物 |
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
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JPWO2007040005A1 (ja) * | 2005-09-06 | 2009-04-16 | 国立大学法人京都大学 | ペルオキシソーム増殖剤応答性受容体PPARα活性化剤、および該活性化剤を含有する特定症状の予防または改善用組成物 |
WO2009054504A1 (fr) * | 2007-10-24 | 2009-04-30 | Suntory Holdings Limited | Agent ligand pour un récepteur activé par les proliférateurs de peroxysomes (ppar) |
JP5563824B2 (ja) * | 2007-10-24 | 2014-07-30 | サントリーホールディングス株式会社 | ペルオキシソーム増殖剤応答性受容体(ppar)のリガンド剤 |
JP2011057556A (ja) * | 2009-09-04 | 2011-03-24 | Iwate Univ | 新規なCa2+シグナル伝達阻害剤 |
JP2014221734A (ja) * | 2013-05-13 | 2014-11-27 | 株式会社エヌ・エル・エー | ジンゲロール類を有効成分として含有する肝細胞活性化剤、並びに該肝細胞活性化剤を含有する固形製剤、液状製剤及び機能性食品 |
WO2018212362A1 (fr) * | 2017-05-19 | 2018-11-22 | 株式会社ヤマノビューティケミカル | Agent pour empêcher la dégradation et l'absorption des hydrates de carbone |
JPWO2018212362A1 (ja) * | 2017-05-19 | 2019-06-27 | 琥珀バイオテクノロジー株式会社 | α−グルコシダーゼ活性抑制剤 |
US11007237B2 (en) | 2017-05-19 | 2021-05-18 | Kohaku Bio Technology Co., Ltd. | Agent for suppressing carbohydrate breakdown and absorption |
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