WO2009093584A1 - 植物由来の高尿酸血症の予防または改善剤 - Google Patents
植物由来の高尿酸血症の予防または改善剤 Download PDFInfo
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- WO2009093584A1 WO2009093584A1 PCT/JP2009/050797 JP2009050797W WO2009093584A1 WO 2009093584 A1 WO2009093584 A1 WO 2009093584A1 JP 2009050797 W JP2009050797 W JP 2009050797W WO 2009093584 A1 WO2009093584 A1 WO 2009093584A1
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- extract
- xanthine oxidase
- glycoside
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- peanut
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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- 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
Definitions
- the present invention relates to a component or chalcone derivative derived from at least one plant material selected from the group consisting of mugwort, cerulecium, chrysanthemum, guava, leaflet, blue mallow, oregano, oyster pear, mint, peanut and pynogenol.
- the present invention relates to a preventive or ameliorating agent for hyperuricemia and a xanthine oxidase inhibitor as active ingredients.
- hyperuricemia a state in which the blood uric acid level is 7.0 mg / dL or more is called hyperuricemia.
- hyperuricemia a state in which the blood uric acid level is 7.0 mg / dL or more.
- blood uric acid crystals will crystallize, and if the uric acid salt accumulates in joints etc., gout attacks with severe pain cause.
- gout nodules are formed under the skin, uric acid crystals accumulate in the kidney and urinary tract, and urinary tract stones are likely to occur.
- appropriately controlling the uric acid level in the blood is the basis for preventing and improving hyperuricemia including gout. Severe gout patients are also considered to be effective in reducing gout attacks, suppressing chronicity, preventing and ameliorating kidney disease by reducing blood uric acid levels to an appropriate level (non- Patent Document 1).
- probenecid uric acid excretion agent
- allopurinol uric acid production inhibitor
- an object of the present invention is to provide a highly safe preventive or ameliorating agent for hyperuricemia and a xanthine oxidase inhibitor.
- extracts such as mugwort, tsutsurenka, chrysanthemum, guava, hakogusa, blue mallow, oregano, oysters, peppermint, purple peanut, peanut and the like and pycnogenol are xanthine It has been found that it has an oxidase inhibitory activity and is extremely effective in the prevention and improvement of hyperuricemia, and the present invention has been completed.
- chalcone derivatives especially okanine or okanine glycoside, have xanthine oxidase inhibitory activity and are extremely useful as a preventive or ameliorating agent for hyperuricemia, thereby completing the present invention.
- R1 to R10 each independently represents any of H, OH, and OCH 3 ), or a glycoside thereof, as an active ingredient.
- a preventive or ameliorating agent for blood glucose. [2] An organic solvent or an organic solvent aqueous solution extract of at least one plant material selected from the group consisting of mugwort, cerulecium, chrysanthemum, guava, leaflet, blue mallow, oregano, oyster, mint, purple peanut, and peanut, Pycnogenol and / or general formula (1):
- R1 to R10 each independently represents any one of H, OH, and OCH 3
- a xanthine oxidase characterized by containing as an active ingredient a chalcone derivative or a glycoside thereof Inhibitor.
- the organic solvent is ethanol.
- the chalcone derivative represented by the general formula (1) or a glycoside thereof is a chalcone derivative derived from a Sendangsa plant or a glycoside thereof. .
- the preventive or ameliorating agent for hyperuricemia and the xanthine oxidase inhibitor of the present invention are derived from plant materials with dietary experience, they are highly safe and have excellent xanthine oxidase inhibitory activity. It is effective for prevention and improvement.
- the preventive or ameliorating agent for hyperuricemia in the present invention is at least one plant selected from the group consisting of mugwort, cethurenka, chrysanthemum, guava, scallop, blue mallow, oregano, oyster duck, mint, purple peanut and peanut.
- An organic solvent or organic solvent aqueous extract, Pycnogenol, and / or chalcone derivative or glycoside thereof can be used as an active ingredient, and can be used for prevention or improvement of hyperuricemia. Furthermore, it can be used to control the uric acid level in blood to an appropriate value.
- the prevention of hyperuricemia in the present invention refers to the state of hyperuricemia defined by the Japanese Society of Gout and Nucleic Acid Metabolism in the Guidelines for Treatment of Hyperuricemia and Gout (issued in September 2002) (in blood It refers to preventing or delaying (reducing the risk) of reaching a uric acid level of 7.0 mg / dL or more.
- the improvement of hyperuricemia as referred to in the present invention refers to reducing the blood uric acid level from the hyperuricemia described above to a normal state or approaching that state.
- the agent for preventing or improving hyperuricemia of the present invention can also be used for preventing or improving gout symptoms by controlling the blood uric acid level.
- a composition containing an extract, pycnogenol, and / or a chalcone derivative or a glycoside thereof as an active ingredient can also be used as a xanthine oxidase inhibitor.
- the xanthine oxidase inhibitor of the present invention can inhibit the production of uric acid by inhibiting the action of xanthine oxidase. Moreover, the xanthine oxidase inhibitor of this invention can also suppress the active oxygen produced when xanthine oxidase produces uric acid from xanthine. In addition, the xanthine oxidase inhibitor of the present invention can be used for various applications that can be expected by inhibiting or suppressing the action of xanthine oxidase.
- the xanthine oxidase inhibitory effect can be measured by administering or ingesting a xanthine oxidase inhibitor as a test substance to a mammal and measuring the effect, or by allowing a test substance to act on a commercially available or prepared xanthine oxidase. It can be evaluated by a method of measuring the inhibitory action. In general, a method using a commercially available or prepared xanthine oxidase is excellent in sensitivity, reproducibility, and simplicity, and this method is usually used.
- xanthine oxidase inhibitory activity can be measured, for example, by using xanthine as a substrate and buttermilk-derived xanthine oxidase as an enzyme and detecting the produced uric acid (Biol. Pharm. Bull., 2004). , Vol. 27, pp. 1414-1421).
- a sample showing 40% or more xanthine oxidase inhibitory activity as compared with the solvent control is determined as “having xanthine oxidase inhibitory activity”.
- the active ingredient of the preventive or ameliorating agent for hyperuricemia of the present invention, and the xanthine oxidase inhibitor (hereinafter collectively referred to as “the agent of the present invention”) or the plant material derived therefrom are mugwort, cerulean, chrysanthemum, guava , Mint, blue mallow, oregano, persimmon, mint, peanut, pynogenol, and / or chalcone derivative or glycoside thereof.
- the above materials can be used alone or in combination of two or more. These plant materials may be those usually provided for food.
- mugwort When using mugwort in the agent of the present invention, it is also possible to use mussel, which is a crude drug using mugwort as a base plant.
- a boxweed in the agent of the present invention it is also possible to use a buckwheat which is a herbal medicine using a boxweed as a base plant.
- kakidooshi When using kakidooshi in the agent of the present invention, it is also possible to use ginseng or lotus root, which is a herbal medicine using kakidooshi as a base plant.
- Murasaki FUJI is used in the agent of the present invention, it is also possible to use caquette which uses Murasaki FUJI Fuji as a base plant.
- Plant materials used in the agent of the present invention such as mugwort, cerulean, chrysanthemum, guava, leaflet, blue mallow, oregano, persimmon, mint, purple peanut, peanut, and the like are leaves, stems, buds, flowers, wood parts, bark, etc. All parts such as the above-ground parts and the underground parts such as roots and tubers, seeds, and resins can be used.
- the whole plant for mugwort the whole plant for Sethlenka, the flower for Chrysanthemum, the leaf for Guava, the whole plant for Jaguagusa, the flower for Blue Mallow, the leaves and flowers for Oregano, the whole plant for Kakidooshi
- leaves for mint stems for purple peas, and astringent skin for peanuts.
- the method for obtaining the plant material extract is not particularly limited, but the above plant material is immersed in an organic solvent or an organic solvent aqueous solution, stirred or left under normal pressure, and subjected to stationary separation, filtration, centrifugation, or the like. Can be obtained.
- the extraction solvent used is an organic solvent or an organic solvent aqueous solution (a mixed solvent of an organic solvent and water), and the organic solvent is not particularly limited, but examples thereof include ethanol, ethyl acetate, acetone, hexane, methanol, and the like. Can be mentioned. Moreover, when using it, mixing with water, a water-soluble organic solvent is preferable.
- the ethanol concentration when an aqueous ethanol solution is used as the extraction solvent is not particularly limited, but is, for example, 50% by weight or more, preferably 90% by weight or more, and more preferably 95% by weight or more.
- the extraction temperature can be suitably carried out generally at -20 to 100 ° C, usually 1 to 90 ° C, preferably 10 to 70 ° C.
- the extraction time is usually 0.1 hours to 1 month, preferably 0.5 hours to 7 days.
- the amount of the extraction solvent used is preferably from 1 to 50 times the amount of mugwort, tsutsurenka, chrysanthemum, guava, leaflet, blue mallow, oregano, oyster, mint, peanut, and 1 part by weight of peanut. More preferably, the amount is not less than twice and not more than 20 times. If the amount is less than 1 time, these plant materials are not sufficiently immersed in the extraction solvent, and the extract recovery rate is low. On the other hand, when the amount is 50 times or more, a container such as an extraction tank used for extraction becomes large, and energy required for solvent removal tends to be extremely large, resulting in a high manufacturing cost.
- the extract of mugwort, cethurenka, chrysanthemum, guava, leaflet, blue mallow, oregano, oyster pear, mint, purple peanut or peanut may be used in the form of an extract or the solvent is removed. Things may be used. Further, it may be in a form dissolved and suspended in another appropriate solvent.
- the extract of the mugwort, selenium, chrysanthemum, guava, leaflet, oregano, oyster pear, peppermint, purple peanut or peanut remains as an extract unless it contains impurities that are inappropriate for food and drink or pharmaceuticals. Or as a crude or semi-purified extract.
- the agent of the present invention can contain pycnogenol as an active ingredient.
- Pycnogenol is an extract extracted from the bark of French coastal pine, and in general, it is also possible to obtain and use what is commercially available as "French coastal pine bark extract” or "Pycnogenol". You may use what extracted the coastal pine bark by the well-known method.
- supplements and health foods containing a high amount of Pycnogenol can be used as they are.
- the agent of the present invention can contain a chalcone derivative or its glycoside as an active ingredient.
- the “chalcone derivative” means the following formula (2):
- a chalcone derivative in which any one or more of position numbers 2 to 6 and 2 ′ to 6 ′ in the above formula (2) is substituted with a hydroxyl group or a methoxy group or a glycoside thereof is used as an active ingredient. That is, the chalcone derivative which is an active ingredient of the agent of the present invention is a chalcone derivative or a glycoside thereof in which R1 to R10 are each independently any one of H, OH and OCH 3 in the general formula (1). It is.
- the chalcone derivative used in the present invention will be described in more detail.
- the substituents R1 to R10 in the general formula (1) are not particularly limited as long as they are independently any combination of H, OH, and OCH 3 . However, not all of R1 to R10 are H, and at least one of them must be substituted with OH or OCH 3 .
- any one or more of R1 to R10 are preferably OH, and more preferably two or more are OH. Also preferably more than three either R1 ⁇ R10 is OH or OCH 3.
- chalcone derivatives include butein (in the general formula (1), R3, R4, R8, and R10 are OH and the rest are H), lanseoletin (in the general formula (1), R3, R4, R6, R8 are OH, R7 is OCH 3 and the rest is H), okinein (in general formula (1), R3, R4, R8 to R10 are OH, and the rest are H), pedicerine (in general formula (1) , R6 to R10 are OCH 3 and the rest is H), pedicin (in general formula (1), R6 and R9 are OH, R7, R8, R10 are OCH 3 and the rest are H), styropsidine (general formula (1 during), with R3, R4, R6, R8, R9 are OH, the remainder are H), Ekinachin (in the general formula (1), in R3, R8 is OH, R5 is OCH 3, and the remaining H), Isorikirichi Genin (in the general formula (1), R3, R8, R10 are OH,
- the sugar residue in the case of using the glycoside of the chalcone derivative is selected from a sugar residue derived from a monosaccharide or an oligosaccharide composed of 2 or 3 sugars.
- monosaccharides that are the basis of these sugar residues include aldoses such as glucose, mannose, arabinose, and xylose, and ketoses such as ribulose and xylulose, and deoxy sugars such as rhamnose and fucose.
- the oligosaccharide include those in which two or more of the same or different monosaccharides are glycosidically bonded. In the present invention, any of these glycosides can be preferably used.
- agents of the present invention among agents containing the chalcone derivative as an active ingredient, those containing at least okanine or okanine glycoside are most preferable.
- the chalcone derivative used as an active ingredient of the agent of the present invention can be obtained by chemical synthesis, but a method obtained by extraction using natural products such as plants is preferred from the viewpoint of safety to the human body. It is.
- chrysanthemum flowers or Sendangsa plants are suitable as the plant used as the material for the extraction method.
- Bendens Pilosa or Bidens frondosa it is more preferable to use Bendens Pilosa or Bidens frondosa.
- the usage form of the chrysanthemum flower or Sendangusa plant in the present invention is not particularly limited, and includes, for example, the raw state, the dried product, and the pulverized product of the dried product.
- the extraction method is not particularly limited as long as the chalcone derivative described in the general formula (1) is extracted.
- the chrysanthemum flower or Sendangsa plant is dried and then pulverized and extracted using an extraction solvent.
- the chalcone derivative can be obtained by separation and purification from the extract by a chromatography technique.
- the extraction solvent used for extraction is not particularly limited, but preferred examples include organic solvents such as ethanol, methanol, ethyl acetate, acetone, hexane, and mixed solvents thereof with water. Moreover, when using it, mixing with water, a water-soluble organic solvent is preferable. Among these, it is preferable to select ethanol or an aqueous ethanol solution from the viewpoint of safely applying the obtained extract to food and pharmaceutical applications.
- the chalcone derivative may be separated and purified by subjecting the extracted treatment solution hydrolyzed with an acid or enzyme to chromatography. Note that an extract containing a chalcone derivative may be used as it is as long as it does not contain an inappropriate impurity.
- the chalcone derivatives or glycosides thereof and plant extracts containing them prevent or improve hyperuricemia and gout symptoms by suppressing the production of uric acid in vivo by expressing xanthine oxidase inhibitory activity It is useful as an agent for hyperuricemia. Furthermore, it can be used to prevent various diseases caused by hyperuricemia or gout. Furthermore, it can be used to prevent diseases caused by active oxygen such as inflammation, arteriosclerosis, carcinogenesis, brain damage, and metabolic syndrome. Also effective for prevention and improvement.
- An active ingredient of the agent of the present invention an extract of the above mugwort, cerulenka, chrysanthemum, guava, scallop, blue mallow, oregano, oyster, mint, purple peanut or peanut organic solvent or organic solvent aqueous solution, pycnogenol, or
- the chalcone derivative or its glycoside can be subjected to operations such as deodorization and purification within a range not losing the xanthine oxidase inhibitory activity.
- the active ingredient in the agent of the present invention is at least one plant material selected from the group consisting of mugwort, celetula, chrysanthemum, guava, mint moth, blue mallow, oregano, persimmon, mint, purple peanut and peanut Or an extract from an organic solvent or an aqueous solution of an organic solvent, pycnogenol, or a chalcone derivative or a glycoside thereof (hereinafter, also simply referred to as “active ingredient”).
- these active ingredients may be contained alone, or mixed with additives such as known carriers and auxiliaries, and used as capsules, tablets, granules, etc. It may be molded into a form that is easy to do.
- various vitamins such as vitamin A, C, D, and E, can also be added and used together for the purpose of nutrient enhancement.
- the content of the active ingredient in the agent of the present invention is not particularly limited, but is preferably 0.1 to 100% by weight, more preferably 10 to 90% by weight.
- the agent of the present invention can also be used as a food, drink, cosmetic or pharmaceutical product containing these.
- the food and drink containing the agent of the present invention is not particularly limited.
- it is mixed with food and drink ingredients and confectionery such as chewing gum, chocolate, candy, jelly, biscuits and crackers; frozen confectionery such as ice cream and ice confectionery ; Beverages such as tea, soft drinks, energy drinks, beauty drinks; Noodles such as udon, Chinese noodles, spaghetti, instant noodles; Kneaded products such as rice cakes, bamboo rings, hampen; Seasonings such as dressings, mayonnaise, sauces; margarine, butter , Oils and fats such as salad oil; can be used for all common foods and drinks such as bread, ham, soup, retort food, frozen food and the like.
- ingredients and confectionery such as chewing gum, chocolate, candy, jelly, biscuits and crackers
- frozen confectionery such as ice cream and ice confectionery
- Beverages such as tea, soft drinks, energy drinks, beauty drinks
- Noodles such as udon, Chinese noodles, spaghetti, instant noodles
- Kneaded products such as
- foods and drinks containing chalcone derivatives or glycosides thereof can be provided, for example, as chrysanthemum juice or sendangsa concentrated extract having an effect of preventing or improving hyperuricemia or having xanthine oxidase inhibitory activity.
- it can be formulated into health functional foods such as foods for specified health use, nutritional functional foods, health foods, and supplements.
- the intake amount is preferably 0.01 to 1000 mg / Kg body weight, more preferably 0.1 to 300 mg / Kg body weight per adult day, in terms of the amount of the above active ingredient. It is preferable to ingest it.
- the dosage form is not particularly limited.
- it may be a powder dried by spray drying or freeze drying.
- capsules such as hard capsules and soft capsules, tablets exemplified by chewable tablets, granules, solutions, powders, injections, suppositories, patches and the like can be mentioned.
- other pharmaceutically acceptable formulation materials such as excipients, disintegrants, lubricants, binders, antioxidants, colorants, anti-aggregation agents, absorption enhancers, solubilizers An agent, a stabilizer and the like can be added as appropriate.
- the dosage of these preparations varies depending on the symptoms, administration method, age of the person to take, weight, etc. Extract of organic material or organic solvent aqueous solution of at least one plant material selected from the group consisting of mugwort, zelkova, chrysanthemum, guava, leaflet, blue mallow, oregano, persimmon, mint, purple peanut, or peanuts, or
- the amount of the above-mentioned active ingredient is preferably 0.01 to 1000 mg / Kg body weight, more preferably 0.1 to 100 mg / Kg body weight per adult, per day. It is preferable to administer in divided doses.
- the intake amount of the chalcone derivative per day for an adult is usually selected in the range of 0.01 to 20 g, preferably 0.05 to 5 g.
- agent of the present invention in combination with other pharmaceuticals, hyperuricemia compositions, foods having xanthine oxidase inhibitory action, and the like.
- Example 1 Mugwort (whole plant), Selenium (whole plant), Dermatosus (whole plant), Kakidoshi (whole plant), mint (leaves), Murasaki Kinafuji (stem) (Purchased from Shinwa Bussan Co., Ltd.); Chrysanthemum (flower) ), Oregano (leaves and flowers) (Purchased from Kaneka Sun Spice Co., Ltd.); Blue Mallow (Flowers) (Purchased from Katsura Kobayashi Co., Ltd.); Guava (Leaf), Peanuts (Astringent Skin) Purchased), 1000 g of each was immersed in 5 L of a 99.5 vol% ethanol aqueous solution and subjected to stirring extraction at 45 degrees for 6 hours, and then the residue was removed by filtration to obtain an extract. Furthermore, the extract was concentrated under reduced pressure to remove the solvent, and each extract was obtained. Pycnogenol was a commercially available product.
- Example 2 In evaluating the xanthine oxidase inhibitory activity of each sample, each extract and pycnogenol prepared in Example 1 were dissolved in DMSO to give 100 mg / mL. Each DMSO solution was dissolved in 75 mM phosphate buffer (pH 7.5) to prepare a 400 ⁇ g / mL sample solution.
- reaction value As a solvent control, 50 ⁇ L of a solution in which DMSO was dissolved to 0.4% in a phosphate buffer was used instead of the sample solution.
- the amount of uric acid produced by xanthine oxidase (reaction value) in the reaction solution to which the solvent control or sample was added was obtained by subtracting the absorbance in the absence of xanthine oxidase from the absorbance in the presence of xanthine oxidase.
- the xanthine oxidase inhibitory activity was calculated
- Table 1 shows the xanthine oxidase inhibitory activity of mugwort, cethurenka, chrysanthemum, guava, boxworm, blue mallow, oregano, oyster pear, mint, peanut extract, and pynogenol obtained in Example 1.
- Example 1 the Artemisia, Settsurenka, Chrysanthemum, Guava, Dermatophora, Blue Mallow, Oregano, Kakidooshi, Mudder, Murasaki Kinafuji, Peanut ethanol extract, and Pycnogenol obtained in Example 1 are strong. Xanthine oxidase inhibitory activity was demonstrated.
- Example 3 In evaluating the xanthine oxidase inhibitory activity of each sample, okanine (derived from American Sendangsa) and allopurinol (manufactured by Wako Pure Chemical Industries, Ltd.) were each dissolved in DMSO to give 100 mM. Each DMSO solution was dissolved in 75 mM phosphate buffer (pH 7.5) to prepare a 400 ⁇ M sample solution.
- reaction value As a solvent control, 50 ⁇ L of DMSO dissolved in phosphate buffer so as to be 0.4% was used instead of the sample solution.
- the xanthine oxidase inhibitory activity was calculated
- Xanthine oxidase inhibitory activity (%) ⁇ 1 ⁇ (reaction value of test substance (sample) / reaction value of solvent control) ⁇ 100 Furthermore, the sample concentration was changed, and the xanthine oxidase inhibitory activity of each sample at various concentrations was determined in the same manner.
- the IC 50 of okanine for xanthine oxidase was compared with the IC 50 of allopurinol used as a hyperuricemia agent.
- the IC 50 for okanine and allopurinol are shown in Table 2.
- IC 50 represents the concentration of the test substance for inhibiting the activity of xanthine oxidase by 50%, assuming that the activity of the solvent control is 100%.
- the okanine of the present invention showed a stronger xanthine oxidase inhibitory activity than allopurinol.
- Example 4 5-week-old male SD rats were purchased from Japan SLC and acclimated for 1 week. Divide into groups based on body weight (6 mice per group) and set a total of 5 groups: control group, mugwort extract administration group, chrysanthemum extract administration group, guava extract administration group, oregano extract administration group did.
- potassium oxonate 250 mg / Kg body weight was administered into the abdominal cavity of a rat to obtain a potassium oxonate-induced hyperuricemia model rat.
- the mugwort extract administration group, chrysanthemum extract administration group, guava extract administration group, and oregano extract administration group were added to the mugwort extract, chrysanthemum extract, guava obtained in Example 1, respectively.
- the extract and the oregano extract were suspended in medium-chain fatty acid triglycerides, and each extract was administered at a dose of 500 mg / Kg body weight.
- medium chain fatty triglycerides were administered to the control group. Subsequently, blood was collected from all individuals 2 hours after administration of potassium oxonate. Serum was collected from the collected blood by centrifugation, and the uric acid level in the blood was measured. Table 3 shows the results.
- Example 5 5-week-old male SD rats were purchased from Japan SLC and acclimated for 1 week. Grouping was performed based on body weight (6 mice per group), and a total of 3 groups were set up: a control group, a seturenka extract-administered group, and a boxworm extract extract-administered group.
- potassium oxonate 250 mg / Kg body weight was administered into the abdominal cavity of a rat to obtain a potassium oxonate-induced hyperuricemia model rat.
- the Cetrenka extract administration group and the Japonica extract administration group were suspended in the medium chain fatty acid triglyceride, respectively, and the extract was 1000 mg. / Kg body weight was administered.
- medium chain fatty triglycerides were administered to the control group.
- blood was collected from all individuals 3 hours after administration of potassium oxonate. Serum was collected from the collected blood by centrifugation, and the uric acid level in the blood was measured. Table 4 shows the results.
- Example 6 5-week-old male SD rats were purchased from Japan SLC and acclimated for 1 week. Grouping (6 animals per group) was carried out based on body weight, and a total of 2 groups were set up: a control group and an okanine administration group.
- potassium oxonate 250 mg / Kg body weight was administered into the abdominal cavity of a rat to obtain a potassium oxonate-induced hyperuricemia model rat.
- okanine was suspended in distilled water and administered so that the okanine was 50 mg / Kg body weight.
- distilled water was administered to the control group.
- blood was collected from all individuals 2 hours after administration of potassium oxonate. Serum was collected from the collected blood by centrifugation, and the uric acid level in the blood was measured. Table 5 shows the results.
- Example 7 Mugwort (whole plant), chrysanthemum (flower), guava (leaf), scallop (whole plant), blue mallow (flower), oregano (leaf and flower), mint (leaf), 1000 g each, 90, 60, 30, After soaking in a volume% ethanol aqueous solution or water and stirring at 45 ° C. for 6 hours, the residue was removed by filtration to obtain an extract. The extract was concentrated under reduced pressure to remove the solvent, and each extract was obtained.
- Example 8 Each extract prepared in Example 7 was dissolved in DMSO to make 100 mg / mL. Each DMSO solution was dissolved in 75 mM phosphate buffer (pH 7.5) to prepare a 400 ⁇ g / mL sample solution.
- reaction value As a solvent control, 50 ⁇ L of a solution in which DMSO was dissolved to 0.4% in a phosphate buffer was used instead of the sample solution.
- the xanthine oxidase inhibitory activity was calculated
- Table 6 shows the xanthine oxidase inhibitory activity of the extract of mugwort, chrysanthemum, guava, boxworm, blue mallow, oregano and mint, obtained in Example 7.
- Example 7 As apparent from Table 6, the extract of mugwort, chrysanthemum, guava, boxweed, blue mallow and oregano obtained in Example 7 showed strong xanthine oxidase inhibitory activity.
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Abstract
Description
[1] ヨモギ、セツレンカ、菊、グアバ、ハハコグサ、ブルーマロー、オレガノ、カキドオシ、ハッカ、ムラサキナツフジおよびピーナッツからなる群より選択される少なくとも1種の植物素材の有機溶媒または有機溶媒水溶液抽出物、ピクノジェノール、および/または、一般式(1):
[2] ヨモギ、セツレンカ、菊、グアバ、ハハコグサ、ブルーマロー、オレガノ、カキドオシ、ハッカ、ムラサキナツフジおよびピーナッツからなる群より選択される少なくとも1種の植物素材の有機溶媒または有機溶媒水溶液抽出物、ピクノジェノール、および/または、一般式(1):
[3] 有機溶媒が、エタノールである[1]または[2]記載の剤。
[4] 一般式(1)で表されるカルコン誘導体またはその配糖体が、センダングサ属植物由来のカルコン誘導体またはその配糖体であることを特徴とする[1]または[2]記載の剤。
[5] 一般式(1)で表されるカルコン誘導体またはその配糖体が、オカニンまたはオカニン配糖体であることを特徴とする[1]または[2]記載の剤。
[6] [1]~[5]のいずれかに記載の剤を含有することを特徴とする飲食品。
[7] 機能性食品である[6]記載の飲食品。
[8] 特定保健用食品である[6]記載の飲食品。
[9] [1]~[5]のいずれかに記載の剤を含有することを特徴とする、化粧品または医薬品。
ヨモギ(全草)、セツレンカ(全草)、ハハコグサ(全草)、カキドオシ(全草)、ハッカ(葉)、ムラサキナツフジ(茎)(以上、新和物産株式会社より購入);菊(花)、オレガノ(葉および花)(以上、株式会社カネカサンスパイスより購入);ブルーマロー(花)(小林桂株式会社より購入);グアバ(葉)、ピーナッツ(渋皮)(以上、一般小売店で購入)、各々1000gを、99.5容量%エタノール水溶液5Lに浸し45度で6時間、撹拌抽出を行った後、ろ過により残渣を除去して抽出液を得た。更に、その抽出液を減圧濃縮して溶媒を除去し、それぞれの抽出物を得た。また、ピクノジェノールは市販品をそのまま使用した。
各サンプルのキサンチンオキシダーゼ阻害活性を評価するにあたり、実施例1で調製した各抽出物およびピクノジェノールを、DMSOに溶解し100mg/mLとした。各々のDMSO溶液を75mMリン酸緩衝液(pH7.5)に溶解し400μg/mLのサンプル溶液を調製した。
キサンチンオキシダーゼ阻害活性(%)
={1-(被検物質(サンプル)の反応値/溶媒対照の反応値)}x100
実施例1で得られた、ヨモギ、セツレンカ、菊、グアバ、ハハコグサ、ブルーマロー、オレガノ、カキドオシ、ハッカ、ムラサキナツフジ、ピーナッツ抽出物およびピクノジェノールのキサンチンオキシダーゼ阻害活性を表1に示した。
各サンプルのキサンチンオキシダーゼ阻害活性を評価するにあたり、オカニン(アメリカセンダングサ由来)およびアロプリノール(和光純薬工業社製)を、それぞれ、DMSOに溶解し100mMとした。各々のDMSO溶液を75mMリン酸緩衝液(pH7.5)に溶解し400μMのサンプル溶液を調製した。
={1-(被検物質(サンプル)の反応値/溶媒対照の反応値)x100
さらに、サンプル濃度を変え、同様にして種々の濃度における各サンプルのキサンチンオキシダーゼ阻害活性を求めた。そして、オカニンのキサンチンオキシダーゼに対するIC50と、高尿酸血症剤として用いられているアロプリノールのIC50を比較した。オカニンならびにアロプリノールのIC50を表2に示した。IC50とは、溶媒対照の活性を100%として、キサンチンオキシダーゼの活性を50%阻害するための被検物質の濃度を表す。
5週齢の雄SDラットを日本SLCより購入し、1週間の馴化飼育を行った。体重を基に群分け(1群あたり6匹ずつ)を実施し、対照群、ヨモギ抽出物投与群、菊抽出物投与群、グアバ抽出物投与群、オレガノ抽出物投与群の計5群を設定した。
5週齢の雄SDラットを日本SLCより購入し、1週間の馴化飼育を行った。体重を基に群分け(1群あたり6匹ずつ)を実施し、対照群、セツレンカ抽出物投与群、ハハコグサ抽出物投与群の計3群を設定した。
5週齢の雄SDラットを日本SLCより購入し、1週間の馴化飼育を行った。体重を基に群分け(1群あたり6匹ずつ)を実施し、対照群、オカニン投与群の計2群を設定した。
ヨモギ(全草)、菊(花)、グアバ(葉)、ハハコグサ(全草)、ブルーマロー(花)、オレガノ(葉および花)、ハッカ(葉)、各々1000gを、90、60、30、容量%エタノール水溶液、または水に浸し45℃で6時間、撹拌抽出を行った後、ろ過により残渣を除去して抽出液を得た。抽出液を減圧濃縮して溶媒を除去し、それぞれの抽出物を得た。
実施例7で調製した各抽出物を、DMSOに溶解し100mg/mLとした。各々のDMSO溶液を75mMリン酸緩衝液(pH7.5)に溶解し400μg/mLのサンプル溶液を調製した。
={1-(被検物質(サンプル)の反応値/溶媒対照の反応値)}x100
実施例7で得られた、ヨモギ、菊、グアバ、ハハコグサ、ブルーマロー、オレガノ、ハッカの各抽出液のキサンチンオキシダーゼ阻害活性を表6に示した。
Claims (9)
- 有機溶媒が、エタノールである請求項1または2記載の剤。
- 一般式(1)で表されるカルコン誘導体またはその配糖体が、センダングサ属植物由来のカルコン誘導体またはその配糖体であることを特徴とする請求項1または2記載の剤。
- 一般式(1)で表されるカルコン誘導体またはその配糖体が、オカニンまたはオカニン配糖体であることを特徴とする請求項1または2記載の剤。
- 請求項1~5いずれか1項記載の剤を含有することを特徴とする飲食品。
- 機能性食品である請求項6記載の飲食品。
- 特定保健用食品である請求項6記載の飲食品。
- 請求項1~5いずれか1項記載の剤を含有することを特徴とする、化粧品または医薬品。
Priority Applications (4)
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EP09703148A EP2251024A4 (en) | 2008-01-23 | 2009-01-21 | MEDICAMENT OF VEGETABLE ORIGIN TO PREVENT OR IMPROVE HYPERURICEMIA |
CN2009801029860A CN101925361A (zh) | 2008-01-23 | 2009-01-21 | 植物来源的高尿酸血症的预防或改善剂 |
JP2009550523A JPWO2009093584A1 (ja) | 2008-01-23 | 2009-01-21 | 植物由来の高尿酸血症の予防または改善剤 |
US12/864,069 US20110038959A1 (en) | 2008-01-23 | 2009-01-21 | Plant-origin drug for preventing or improving hyperuricemia |
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JP2008-012910 | 2008-01-23 | ||
JP2008012910 | 2008-01-23 | ||
JP2008-034209 | 2008-02-15 | ||
JP2008034209 | 2008-02-15 |
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WO2009093584A1 true WO2009093584A1 (ja) | 2009-07-30 |
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US (1) | US20110038959A1 (ja) |
EP (1) | EP2251024A4 (ja) |
JP (1) | JPWO2009093584A1 (ja) |
CN (1) | CN101925361A (ja) |
WO (1) | WO2009093584A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013516477A (ja) * | 2010-01-07 | 2013-05-13 | コルゲート・パーモリブ・カンパニー | カルコン含有口腔ケア配合物の色の変化 |
JP2021008445A (ja) * | 2019-06-28 | 2021-01-28 | 国立大学法人 東京大学 | Urat1阻害剤及びurat1阻害用飲食品組成物 |
JP2021527101A (ja) * | 2018-06-13 | 2021-10-11 | ベイラー カレッジ オブ メディスンBaylor College Of Medicine | 高尿酸血症および酸化ストレスを制御するための健康食品サプリメントおよび抗酸化物質の開発 |
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EP2322193B1 (en) * | 2008-07-07 | 2018-04-11 | Kao Corporation | Xanthine oxidase inhibitor and uric acid production inhibitor |
JP6721905B2 (ja) * | 2015-09-25 | 2020-07-15 | サッポロホールディングス株式会社 | 血中尿酸値低下剤 |
CN107126450B (zh) * | 2016-02-26 | 2020-12-25 | 上海医药工业研究院 | 鼠麹草提取物、鼠麹草有效物质富集物,制备方法与应用 |
CN107126449A (zh) * | 2016-02-26 | 2017-09-05 | 上海医药工业研究院 | 鼠麹草提取物,及其制备方法与应用 |
CN106072560A (zh) * | 2016-06-29 | 2016-11-09 | 傅志勇 | 一种用于治疗痛风的保健品及其制备方法 |
CN107951922A (zh) * | 2017-12-08 | 2018-04-24 | 杨英珠 | 赤苍藤降酸茶及其制备方法 |
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CN114515005B (zh) * | 2022-01-27 | 2024-04-05 | 华南理工大学 | 一种含有菊花成分的薏苡仁提取物及其制备方法与应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6140763A (ja) * | 1984-08-02 | 1986-02-27 | Osaka Chem Lab | 抗肥満食品 |
JP2006036787A (ja) | 2005-09-29 | 2006-02-09 | Fancl Corp | キサンチンオキシダーゼ阻害剤 |
JP2007045784A (ja) | 2005-08-12 | 2007-02-22 | Kikkoman Corp | 新規エラグ酸誘導体及びキサンチンオキシダーゼ阻害剤 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1136073A1 (en) * | 2000-03-22 | 2001-09-26 | N.V. Nutricia | Compositions suitable for the treatment of damage caused by ischemia/reperfusion or oxidative stress |
-
2009
- 2009-01-21 CN CN2009801029860A patent/CN101925361A/zh active Pending
- 2009-01-21 US US12/864,069 patent/US20110038959A1/en not_active Abandoned
- 2009-01-21 WO PCT/JP2009/050797 patent/WO2009093584A1/ja active Application Filing
- 2009-01-21 EP EP09703148A patent/EP2251024A4/en not_active Withdrawn
- 2009-01-21 JP JP2009550523A patent/JPWO2009093584A1/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6140763A (ja) * | 1984-08-02 | 1986-02-27 | Osaka Chem Lab | 抗肥満食品 |
JP2007045784A (ja) | 2005-08-12 | 2007-02-22 | Kikkoman Corp | 新規エラグ酸誘導体及びキサンチンオキシダーゼ阻害剤 |
JP2006036787A (ja) | 2005-09-29 | 2006-02-09 | Fancl Corp | キサンチンオキシダーゼ阻害剤 |
Non-Patent Citations (6)
Title |
---|
BIOL. PHARM. BULL., vol. 27, 2004, pages 1414 - 1421 |
JAPANESE SOCIETY OF GOUT AND NUCLEIC ACID METABOLISM, September 2002 (2002-09-01) |
MEBIO, vol. 17, 2000, pages 24 - 29 |
PURINE-PYRIMIDINE TAISHA (METABOLISM), vol. 18, 1994, pages 1 - 10 |
See also references of EP2251024A1 * |
YUN, KYEONG WON ET AL.: "The influence of the growth season on the antimicrobial and antioxidative activity in Artemisia princeps var. orientalis", INDUSTRIAL CROPS AND PRODUCTS, vol. 27, no. 1, January 2008 (2008-01-01), pages 69 - 74, XP022368453 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2013516477A (ja) * | 2010-01-07 | 2013-05-13 | コルゲート・パーモリブ・カンパニー | カルコン含有口腔ケア配合物の色の変化 |
US8784779B2 (en) | 2010-01-07 | 2014-07-22 | Colgate-Palmolive Company | Color change of chalcone-containing oral care formulations |
US9265703B2 (en) | 2010-01-07 | 2016-02-23 | Colgate-Palmolive Company | Color change of chalcone-containing oral care formulations |
JP2021527101A (ja) * | 2018-06-13 | 2021-10-11 | ベイラー カレッジ オブ メディスンBaylor College Of Medicine | 高尿酸血症および酸化ストレスを制御するための健康食品サプリメントおよび抗酸化物質の開発 |
JP7343192B2 (ja) | 2018-06-13 | 2023-09-12 | ベイラー カレッジ オブ メディスン | 高尿酸血症および酸化ストレスを制御するための健康食品サプリメントおよび抗酸化物質の開発 |
JP2021008445A (ja) * | 2019-06-28 | 2021-01-28 | 国立大学法人 東京大学 | Urat1阻害剤及びurat1阻害用飲食品組成物 |
JP7376889B2 (ja) | 2019-06-28 | 2023-11-09 | 国立大学法人 東京大学 | Urat1阻害剤及びurat1阻害用飲食品組成物 |
Also Published As
Publication number | Publication date |
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CN101925361A (zh) | 2010-12-22 |
EP2251024A4 (en) | 2011-12-28 |
JPWO2009093584A1 (ja) | 2011-05-26 |
EP2251024A1 (en) | 2010-11-17 |
US20110038959A1 (en) | 2011-02-17 |
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