WO2018155150A1 - Blood uric acid level improving agent and food/drink for improving blood uric acid level - Google Patents

Blood uric acid level improving agent and food/drink for improving blood uric acid level Download PDF

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Publication number
WO2018155150A1
WO2018155150A1 PCT/JP2018/003851 JP2018003851W WO2018155150A1 WO 2018155150 A1 WO2018155150 A1 WO 2018155150A1 JP 2018003851 W JP2018003851 W JP 2018003851W WO 2018155150 A1 WO2018155150 A1 WO 2018155150A1
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uric acid
acid level
blood uric
hesperidin
food
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PCT/JP2018/003851
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French (fr)
Japanese (ja)
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拓 平田
愛美 紺谷
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サッポロホールディングス株式会社
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Publication of WO2018155150A1 publication Critical patent/WO2018155150A1/en

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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
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • 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

Definitions

  • the present invention relates to a blood uric acid level improving agent and a food and drink for improving blood uric acid level.
  • Hyperuricemia refers to a high blood uric acid level, which causes gout. Therefore, improving blood uric acid levels leads to prevention of hyperuricemia.
  • Various developments have been made so far for the purpose of preventing hyperuricemia.
  • Patent Document 1 discloses a plasma uric acid level-lowering agent containing a lemon extract obtained by extraction with a polar solvent selected from methanol, ethanol, and water as an active ingredient. .
  • An object of the present invention is to provide a novel blood uric acid level improving agent.
  • the present invention relates to a blood uric acid level improving agent comprising monoglucosyl hesperidin as an active ingredient.
  • the blood uric acid level improving agent according to the present invention contains monoglucosyl hesperidin as an active ingredient, the blood uric acid level can be improved.
  • the blood uric acid level improving agent according to the present invention is preferably an enzyme-treated hesperidin containing monoglucosyl hesperidin as an active ingredient.
  • the enzyme-treated hesperidin is preferably an enzyme-treated product of lemon extract.
  • the lemon extract is preferably a green lemon extract.
  • the blood uric acid level improving agent according to the present invention is preferably for long-term administration. Thereby, the blood uric acid level improving action is further improved.
  • the blood uric acid level improving agent according to the present invention contains monoglucosyl hesperidin as an active ingredient. Since monoglucosyl hesperidin has good water solubility, it can be dissolved or dispersed uniformly even when added to water or foods with a high water content, and therefore can be suitably used as a food or drink. Therefore, this invention relates also to the food-drinks for blood uric acid level improvement which use monoglucosyl hesperidin as an active ingredient.
  • the present invention can also be said to be a method for improving blood uric acid level, which comprises administering monoglucosyl hesperidin to a subject in need thereof.
  • the present invention can also be referred to as the use of monoglucosyl hesperidin for the production of a blood uric acid level improving agent.
  • the present invention can also be referred to as monoglucosyl hesperidin for use in improving blood uric acid levels.
  • a novel blood uric acid level improving agent can be provided.
  • Example 3 is a graph showing the results of Example 1.
  • 10 is a graph showing the results of Example 2.
  • 6 is a graph showing the results of Reference Example 1.
  • the blood uric acid level improving agent according to this embodiment contains monoglucosyl hesperidin as an active ingredient.
  • the blood uric acid level improving agent according to the present embodiment can control the blood uric acid level within a normal range or a value close to the normal range. Therefore, the blood uric acid level improving agent according to the present embodiment can also be referred to as a blood uric acid level control agent, a blood uric acid level increase inhibitor, and a blood uric acid level lowering agent.
  • the reference value of blood uric acid level is about 2.1 to 7.0 mg / dL.
  • Monoglucosyl hesperidin is a compound in which one glucose is bonded to a glucose residue in a rutinose unit of hesperidin, which is one of polyphenols contained in citrus, by an ⁇ -1,4 bond.
  • Monoglucosyl hesperidin may be a commercially available product, or may be obtained by chemical synthesis, and obtained by subjecting hesperidin to an enzyme treatment with a glycosyltransferase (eg, cyclodextrin glucosyltransferase). A thing may be used.
  • a glycosyltransferase eg, cyclodextrin glucosyltransferase
  • the blood uric acid level improving agent according to the present embodiment preferably contains enzyme-treated hesperidin containing monoglucosyl hesperidin as an active ingredient.
  • enzyme-treated hesperidin is synonymous with “enzyme-treated hesperidin” described in the list of items in the existing additive list (Japan Food Chemistry Research Foundation, revised on January 30, 2014). .
  • Enzyme-treated hesperidin is an enzyme-treated product of hesperidin and contains hesperetin glycosides such as hesperidin, ⁇ -glucosyl hesperidin, and 7-glucosyl hesperetin.
  • ⁇ -glucosyl hesperidin is a compound (glycosylated hesperidin) in which one or more glucose is bonded to a glucose residue in the rutinose unit of hesperidin by ⁇ -1,4 bond, and includes monoglucosyl hesperidin.
  • the enzyme-treated hesperidin according to this embodiment includes monoglucosyl hesperidin.
  • the content of monoglucosyl hesperidin in the enzyme-treated hesperidin may be 50 to 95 w / w%, preferably 60 to 90 w / w%, more preferably 75 to 95% based on the total amount of enzyme-treated hesperidin. It may be 85 w / w%.
  • the monoglucosyl hesperidin content in the enzyme-treated product of the lemon extract is within the above range, the blood uric acid level improving effect is further improved.
  • hesperidin When enzyme-treated hesperidin is obtained from hesperidin by enzymatic treatment, hesperidin may be one obtained by extraction from citrus fruits, one commercially available, or one obtained by chemical synthesis. Although it is good, it is preferable to use what was obtained by extraction from citrus fruits.
  • citrus fruits examples include lemon, mandarin orange and lime. These citrus fruits may be used alone or in combination of two or more.
  • the citrus fruits are preferably lemons. Thereby, since the odor derived from the extraction raw material becomes a low odor, it becomes excellent in flavor.
  • Examples of the enzyme-treated hesperidin of an extract of hesperidin derived from mandarin orange and Daidai include “ ⁇ G Hesperidin PS” and “ ⁇ G Hesperidin PA-T” manufactured by Toyo Seika Co., Ltd.
  • ⁇ G Hesperidin PS contains 85% by mass of monoglucosyl hesperidin, 1% by mass of hesperidin, and 10% by mass of 7-glucosyl hesperetin, and does not contain hesperetin.
  • “ ⁇ G Hesperidin PA-T” contains 85% by mass of monoglucosyl hesperidin and 10% by mass of hesperidin, and does not contain 7-glucosyl hesperetin and hesperetin.
  • the enzyme-treated hesperidin of the lemon-derived hesperidin extract for example, it can also be produced according to the method described in JP-A-2005-343865.
  • the lemon is preferably green lemon.
  • the green lemon means a lemon in which the peel of the lemon at the time of harvest is in a green state, so-called lemon fruit.
  • the raw material (extraction raw material) used for extraction from lemon is lemon fruit or its constituents.
  • the constituent components of fruits include fruit skin, fruit juice, scabbard, potato and seeds. From the viewpoint of easily obtaining a large amount of hesperidin among fruits or constituents thereof, it is preferable to use a peel as an extraction raw material.
  • the extraction raw material may be subjected to processing such as drying, freezing, processing, pulverization, and selection.
  • Extraction from lemon can be performed by immersing lemon in a solvent and filtering it.
  • a solvent for example, water, an alkaline aqueous solution such as an aqueous sodium hydroxide solution, an alcohol such as ethanol, or the like can be used.
  • a solvent may be used individually by 1 type, or may be used in combination of 2 or more type.
  • the lemon extract containing hesperidin can be obtained, for example, by immersing the lemon in an alkaline aqueous solution (for example, an aqueous sodium hydroxide solution), filtering it, and precipitating it under acidic conditions.
  • an alkaline aqueous solution for example, an aqueous sodium hydroxide solution
  • Enzyme-treated hesperidin is a porous synthetic adsorption resin, ion-exchange resin, after allowing hesperidin-containing material to act on a glycosyltransferase such as cyclodextrin glucanotransferase in the presence of a sugar donor such as starch, dextrin or oligosaccharide. And it can be obtained as an enzyme-treated product of hesperidin by subjecting it to a treatment such as carbon treatment.
  • the enzyme-treated product may be further treated with another enzyme (for example, a sugar hydrolase such as glucoamylase), and is purified and separated using a chromatographic separation apparatus or the like. Also good.
  • the enzyme-treated hesperidin is preferably an enzyme-treated product of a lemon extract.
  • the lemon extract is preferably a green lemon extract.
  • the analysis of monoglucosyl hesperidin and enzyme-treated hesperidin can be performed using a known method (for example, HPLC under the conditions described in the 8th edition Food Additives Official Document (Ministry of Health, Labor and Welfare).
  • the blood uric acid level improving agent contains monoglucosyl hesperidin as an active ingredient, the blood uric acid level can be improved by ingestion. Further, if a state in which the blood uric acid value concentration is high continues, it causes gout, but gout can be prevented by improving the blood uric acid value concentration. Therefore, the blood uric acid level improving agent can be used for preventing gout onset and recurrence.
  • the blood uric acid level improving agent according to the present embodiment may be in any shape such as a solid (for example, a powder), a liquid (a water-soluble or fat-soluble solution or suspension), a paste, or the like. , Tablets, capsules, solutions, suspensions, emulsions, ointments, plasters and the like. It can also take the form of a controlled release formulation.
  • the blood uric acid level improving agent according to this embodiment may be administered (ingested) to humans or administered to non-human mammals.
  • the dose (intake) of the blood uric acid level improving agent according to the present embodiment may be, for example, 10 mg to 1000 mg per day, preferably 50 mg to 800 mg, more preferably, based on monoglucosyl hesperidin. , 100 mg to 600 mg.
  • the blood uric acid level improving agent according to this embodiment may be administered orally or parenterally, but is preferably administered orally.
  • the blood uric acid level-improving agent may be administered once a day, or may be administered in a plurality of times a day as long as the dose per day is within the above range.
  • the blood uric acid level improving agent according to this embodiment can be used not only for transient blood uric acid level improvement but also for blood uric acid level improvement by long-term administration.
  • long-term administration means continuous administration (ingestion) over a period of 8 days or more.
  • the blood uric acid level improving agent according to this embodiment can be suitably used for long-term administration.
  • the blood uric acid level improving agent becomes more prominent in blood uric acid level improving effect by long-term administration.
  • the blood uric acid level improving agent according to this embodiment is preferably administered over a period of 8 days or more, more preferably administered over a period of 2 weeks or more, and administration over a period of 4 weeks or more. Is more preferable.
  • the blood uric acid level improving agent according to the present embodiment can be used as a component of products such as pharmaceuticals, quasi drugs, food and drink (beverages and foods), food and drink additives, feed and feed additives.
  • the product comprising the blood uric acid level improving agent according to the present embodiment or containing the blood uric acid level improving agent may be for blood uric acid level improvement, for blood uric acid level control, blood It may be for suppressing the increase in the middle uric acid level, for lowering the blood uric acid level, or for maintaining the blood uric acid level.
  • the above products improve blood uric acid level, control blood uric acid level, suppress blood uric acid level rise, reduce blood uric acid level, optimize blood uric acid level, For those who are concerned about the pudding of food, those who like liquor and delicious food may be displayed.
  • the food and drink for improving blood uric acid level contains monoglucosyl hesperidin as an active ingredient. Thereby, the blood uric acid level can be improved.
  • the enzyme-treated hesperidin is preferably an enzyme-treated product of lemon extract.
  • the lemon extract is preferably a green lemon extract.
  • the intake of the food for improving blood uric acid level may be, for example, 10 mg to 1000 mg per day, preferably 50 mg to 800 mg, more preferably 100 mg, based on monoglucosyl hesperidin. ⁇ 600 mg.
  • the intake of the food and beverage for improving blood uric acid level may be, for example, 13 mg to 1300 mg per day, preferably 65 mg to 1040 mg, more preferably, based on the enzyme-treated hesperidin. 130 mg to 780 mg.
  • the above-mentioned food and drink for improving blood uric acid level include beverages for improving blood uric acid level and foods for improving blood uric acid level.
  • the food / beverage product for improving blood uric acid level according to the present embodiment is not limited to transient blood uric acid level improvement, but can be used for blood uric acid level improvement by long-term administration.
  • beverage for improving blood uric acid level examples include soft drinks, fruit juice drinks, milk drinks, carbonated drinks, alcoholic drinks, non-alcoholic drinks, beer-taste drinks, sports drinks, and nutrition drinks.
  • Examples of the food for improving blood uric acid level include breads, noodles, rice, tofu, dairy products, soy sauce, miso, confectionery, and supplements. It can also be used as an ingredient involved in health foods, functional labeling foods, special-purpose foods, dietary supplements, supplements or foods for specified health use.
  • the food and drink for improving blood uric acid level may contain other components (additives) as long as the effects of the present invention are not impaired.
  • Other ingredients include, for example, sweeteners, flavorings, acidulants, colorants, antioxidants, seasonings, vitamins, minerals, pH adjusters, stabilizers, gelling agents, dietary fiber, and indigestible Dextrin and the like can be used. These components can be used individually by 1 type or in combination of 2 or more types.
  • Sweeteners include sugar, tri-sugar, brown sugar, honey, reduced starch saccharified, oligosaccharides, sugar alcohols, sugars such as rare sugars, sucralose, aspartame, acesulfame potassium, saccharin, alitame, neotame, etc. Sweeteners and the like can be used. These sweeteners can be used alone or in combination of two or more.
  • any natural or synthetic fragrance can be used. Although it does not specifically limit as a fragrance
  • flavors can be used individually by 1 type or in combination of 2 or more types.
  • the sour agent can be used without particular limitation as long as it is used for food and drink.
  • the acidulant for example, citric acid, lactic acid, malic acid, phosphoric acid, succinic acid, tartaric acid, acetic acid and the like can be used. These acidulants can be used alone or in combination of two or more.
  • coloring agent any natural coloring agent or synthetic coloring agent can be used as long as it is used for coloring food and drink.
  • colorant for example, caramel color, gardenia color, marigold color, carotene color, anthocyanin color, fruit juice color, vegetable color, synthetic color and the like can be used.
  • dyes can be used individually by 1 type or in combination of 2 or more types.
  • the food and drink for improving blood uric acid level may be a container-packed food and drink.
  • a container in the case of a container-packed food or drink for example, a glass bottle, a resin molded container, a metal can, a metal foil, a paper container combined with a plastic film, or the like can be used, as in a general food or drink.
  • the type, shape and color of the container are not particularly limited.
  • Examples of the resin constituting the resin-molded container include polyester resins such as polyethylene terephthalate and polybutylene terephthalate, and polyolefins such as polyethylene, polypropylene, and polybutylene.
  • the weight average molecular weight, crystallinity, and the like of these resins are not particularly limited, and can be appropriately selected according to the distribution conditions, storage conditions, and the like of the food and drink.
  • a resin-made container using polyethylene terephthalate is generally called a PET bottle. PET bottles are classified into aseptic PET bottles assuming normal temperature filling (aseptic filling) of foods and drinks, filling foods and drinks while performing heat sterilization, or heat-resistant PET bottles assuming hot sales. However, any of them can be used in the present embodiment.
  • metal cans examples include steel cans, aluminum cans and tin cans.
  • ⁇ / RTI> When the food / beverage for improving blood uric acid level according to the present embodiment is used as a container-packed food / beverage, sterilization may be performed as necessary.
  • Examples of the sterilization and container filling in the case of a container-packed food / beverage product include heat sterilization under conditions defined in the Food Sanitation Law after filling a metal can.
  • a method for improving blood uric acid level comprising administering monoglucosyl hesperidin to a subject in need thereof.
  • use of monoglucosyl hesperidin for manufacture of a blood uric acid level improving agent is provided as one Embodiment of this invention.
  • monoglucosyl hesperidin for use in improving blood uric acid levels is provided.
  • the administration method, administration subject, dosage and the like may be the same as those in the blood uric acid level improving agent.
  • the reaction solution was passed through a column packed with a porous synthetic resin adsorbent (trade name “HP-10”, manufactured by Mitsubishi Kasei Co., Ltd.) at SV 2.0 to adsorb enzyme-treated hesperidin.
  • a porous synthetic resin adsorbent trade name “HP-10”, manufactured by Mitsubishi Kasei Co., Ltd.
  • this column was washed with water to wash and remove dextrin decomposition products and odorous substances, and then passed through a 50 v / v% aqueous ethanol solution to desorb enzyme-treated hesperidin and the like.
  • the obtained desorption solution was concentrated to remove ethanol in the eluate to obtain a dry powder.
  • powdered activated carbon (trade name “Purified Shirakaba”, manufactured by Takeda Food Industry Co., Ltd.) was added to the obtained effluent and stirred at 60 ° C. for 1 hour. Next, the powdered activated carbon was removed by filtration, followed by concentration and drying to obtain a powdered green lemon extract enzyme-treated product (hereinafter also referred to as “GLPP”) as enzyme-treated hesperidin.
  • GLPP powdered green lemon extract enzyme-treated product
  • GLPP contains a high content of monoglucosyl hesperidin.
  • Example 1 Acute test
  • SD rats male, 5 weeks old were bred for 1 week under free feeding conditions of CRF-1 feed (Oriental Yeast Co., Ltd.) and tap water under the breeding conditions of a temperature of 23 ⁇ 1 ° C. and a humidity of 55%.
  • Five animals (GLPP group) were orally administered GLPP at 500 mg / kg, and oxonic acid was administered intraperitoneally at 250 mg / kg 2 hours after GLPP administration, and changes in blood uric acid levels over time were examined. Further, in the same manner as described above except that GLPP was not administered, the same amount of sterile physiological saline was orally administered to the control group, and the change in blood uric acid level over time was examined.
  • the blood uric acid level was measured at 0, 1, 2, and 4 hours with reference to the time point of administration of oxonic acid (0 hour), and the measurement sample was obtained by collecting blood from the rat tail vein. Moreover, the change rate of the blood uric acid level was calculated based on the blood uric acid level (1.0) of each individual 2 hours before the oxonic acid administration (in the GLPP group, at the time of GLPP administration).
  • uric acid synthesized in the purine metabolism pathway is rapidly metabolized to allantoin by an enzyme called uricase, and thus the serum uric acid level is usually kept low. Therefore, a rat in which uric acid metabolism was suppressed by oxonic acid, a uricase inhibitor, was used as a hyperuricemia model rat.
  • the blood uric acid level was measured by the following method. Specifically, 90 ⁇ L of distilled water was added to 10 ⁇ L of the serum to be measured, diluted, and further 20 ⁇ L of 10% trichloroacetic acid / water was added to remove protein. After mixing, the vortexed sample was allowed to stand on ice for 30 minutes and centrifuged. (15,000 rpm, 10 min, 4 ° C.). The obtained supernatant was filtered through a 0.45 ⁇ m filter and subjected to LC-MS / MS analysis under the following conditions. As a sample, uric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was used.
  • Fig. 1 shows the rate of change of uric acid value measurement results.
  • the value of the graph represents the average value of the uric acid value change rate in each group, and the error bar represents its standard error.
  • FIG. 1 it was shown that the increase in blood uric acid level was suppressed by ingesting GLPP containing monoglucosyl hesperidin before the treatment for increasing the uric acid level in rats.
  • mice 7-week-old, C57BL / 6J mice, Charles River
  • mice were subjected to testing at the age of 8 weeks after one week of acclimatization.
  • the mice were housed in an environment with a temperature of 23 ⁇ 1 ° C., a humidity of 55%, and a 12-hour light-dark cycle.
  • the feed during the acclimatization period was MF feed (Oriental Yeast Co., Ltd.), and feed and tap water were freely consumed.
  • the GLPP group fed with a diet mixed with 0.5% and 1.0% GLPP is hereinafter also referred to as “0.5% GLPP group” and “1.0% GLPP group”, respectively.
  • the 60% fructose diet contained in the test diet is a diet that increases the uptake of glucose without insulin through the liver and promotes the synthesis of purine, a substrate for uric acid, and has been reported to increase serum uric acid levels in mice Has been. Further, as in Example 1, hyperuricemia model mice were prepared by feeding with potassium oxonate, which is a uricase inhibitor. Furthermore, 3% uric acid was mixed.
  • Fig. 2 shows the measurement results of blood uric acid levels.
  • the results of measurement of blood uric acid levels in mice of each group at 0 weeks, 2 weeks and 4 weeks after the start of the test are shown in FIGS. 2 (a), 2 (b) and 2 (c), respectively.
  • the value in the graph represents the average value of blood uric acid in each group, and the error bar represents the standard error. 0.5% and 1% in the table indicate “0.5% GLPP group” and “1.0% GLPP group”, respectively.
  • FIG. 2 it was shown that an increase in blood uric acid level was suppressed by ingesting GLPP containing monoglucosyl hesperidin. That is, a significant difference can be confirmed by t-test in the 0.5% and 1.0% GLPP groups at both 2 weeks and 4 weeks, and a significant long-term increase in blood uric acid level is suppressed. I was able to confirm that.
  • the rate of decrease in blood uric acid level after 2 weeks was 27% and 31%, respectively, and the rate of decrease in blood uric acid level after 4 weeks was 35 respectively. % And 38%.
  • the rate of decrease in blood uric acid level (%) is the difference between the blood uric acid level (average value) of the control group mice and the blood uric acid level (average value) of the GLPP group mice. It is the ratio to the blood uric acid level (average value) of the group mice.
  • mice (7-week-old, C57BL / 6J mice, Charles River) were subjected to testing at the age of 8 weeks after one week of acclimatization. Throughout the acclimatization period and subsequent test periods, the mice were housed in an environment with a temperature of 23 ⁇ 1 ° C., a humidity of 55%, and a 12-hour light-dark cycle. The feed during the acclimatization period was MF feed (Oriental Yeast Co., Ltd.), and feed and tap water were freely consumed.
  • MF feed Oriental Yeast Co., Ltd.
  • hesperidin administration test 2-3 animals / cage were housed in a plastic ino cage for 2 weeks.
  • 0.39% hesperidin corresponds to 0.50% GLPP.
  • FIG. 3 shows the measurement results of blood uric acid levels in the hesperidin group and the control group.
  • the blood uric acid level measurement results of the mice in each group at 0 and 2 weeks after the start of the test are shown in FIGS. 3 (a) and 3 (b).
  • the value in the graph represents the average value of blood uric acid in each group, and the error bar represents the standard error.

Abstract

The present invention pertains to a blood uric acid level improving agent having monoglucosyl hesperidin as an active ingredient.

Description

血中尿酸値改善剤及び血中尿酸値改善用飲食品Blood uric acid level improving agent and food and drink for improving blood uric acid level
　本発明は、血中尿酸値改善剤及び血中尿酸値改善用飲食品に関する。 The present invention relates to a blood uric acid level improving agent and a food and drink for improving blood uric acid level.
　高尿酸血症は血中尿酸値が高い状態を指し、痛風の原因となる。そのため、血中尿酸値を改善することは高尿酸血症の予防につながる。これまでにも、高尿酸血症の予防を目的として様々な開発がなされている。 Hyperuricemia refers to a high blood uric acid level, which causes gout. Therefore, improving blood uric acid levels leads to prevention of hyperuricemia. Various developments have been made so far for the purpose of preventing hyperuricemia.
　例えば、特許文献１には、メタノール、エタノール、及び水から選ばれる極性溶媒により抽出して得られるレモン抽出物を有効成分として含有することを特徴とする血漿中尿酸値低下剤が開示されている。 For example, Patent Document 1 discloses a plasma uric acid level-lowering agent containing a lemon extract obtained by extraction with a polar solvent selected from methanol, ethanol, and water as an active ingredient. .
特許第５５４５６９２号公報Japanese Patent No. 5545692
　本発明は、新規な血中尿酸値改善剤を提供することを目的とする。 An object of the present invention is to provide a novel blood uric acid level improving agent.
　本発明は、モノグルコシルヘスペリジンを有効成分とする、血中尿酸値改善剤に関する。 The present invention relates to a blood uric acid level improving agent comprising monoglucosyl hesperidin as an active ingredient.
　本発明に係る血中尿酸値改善剤は、モノグルコシルヘスペリジンを有効成分とするため、血中尿酸値を改善することができる。 Since the blood uric acid level improving agent according to the present invention contains monoglucosyl hesperidin as an active ingredient, the blood uric acid level can be improved.
　本発明に係る血中尿酸値改善剤は、モノグルコシルヘスペリジンを含む酵素処理ヘスペリジンを有効成分とするものであることが好ましい。 The blood uric acid level improving agent according to the present invention is preferably an enzyme-treated hesperidin containing monoglucosyl hesperidin as an active ingredient.
　本発明に係る血中尿酸値改善剤は、上記酵素処理ヘスペリジンがレモン抽出物の酵素処理物であることが好ましい。これにより、抽出原料に由来する臭気が低臭気となるため香味に優れたものとなる。 In the blood uric acid level improving agent according to the present invention, the enzyme-treated hesperidin is preferably an enzyme-treated product of lemon extract. Thereby, since the odor derived from the extraction raw material becomes a low odor, it becomes excellent in flavor.
　上記レモン抽出物は、グリーンレモン抽出物であることが好ましい。 The lemon extract is preferably a green lemon extract.
　本発明に係る血中尿酸値改善剤は、長期投与用であることが好ましい。これにより、血中尿酸値改善作用がより一層優れたものとなる。 The blood uric acid level improving agent according to the present invention is preferably for long-term administration. Thereby, the blood uric acid level improving action is further improved.
　本発明に係る血中尿酸値改善剤は、モノグルコシルヘスペリジンを有効成分としている。モノグルコシルヘスペリジンは、水溶性が良好であるため、水もしくは水分の多い食品に添加する際も、均一に溶解ないし分散させることが可能であるため、飲食品として好適に用いることができる。したがって、本発明はまた、モノグルコシルヘスペリジンを有効成分とする、血中尿酸値改善用飲食品にも関する。 The blood uric acid level improving agent according to the present invention contains monoglucosyl hesperidin as an active ingredient. Since monoglucosyl hesperidin has good water solubility, it can be dissolved or dispersed uniformly even when added to water or foods with a high water content, and therefore can be suitably used as a food or drink. Therefore, this invention relates also to the food-drinks for blood uric acid level improvement which use monoglucosyl hesperidin as an active ingredient.
　本発明は、モノグルコシルヘスペリジンを、それを必要とする対象に投与することを含む、血中尿酸値の改善方法ということもできる。本発明はまた、血中尿酸値改善剤の製造のための、モノグルコシルヘスペリジンの使用ということもできる。本発明は更に、血中尿酸値の改善に使用するための、モノグルコシルヘスペリジンということもできる。 The present invention can also be said to be a method for improving blood uric acid level, which comprises administering monoglucosyl hesperidin to a subject in need thereof. The present invention can also be referred to as the use of monoglucosyl hesperidin for the production of a blood uric acid level improving agent. The present invention can also be referred to as monoglucosyl hesperidin for use in improving blood uric acid levels.
　本発明によれば、新規な血中尿酸値改善剤を提供することができる。 According to the present invention, a novel blood uric acid level improving agent can be provided.
実施例１の結果を示すグラフである。3 is a graph showing the results of Example 1. 実施例２の結果を示すグラフである。10 is a graph showing the results of Example 2. 参考例１の結果を示すグラフである。6 is a graph showing the results of Reference Example 1.
　以下、本発明を実施するための形態について詳細に説明する。なお、本発明は、以下の実施形態に限定されるものではない。 Hereinafter, embodiments for carrying out the present invention will be described in detail. In addition, this invention is not limited to the following embodiment.
　本実施形態に係る血中尿酸値改善剤は、モノグルコシルヘスペリジンを有効成分とする。本実施形態に係る血中尿酸値改善剤は、血中尿酸値を正常な範囲内、又は正常な範囲に近い値に制御することができる。したがって、本実施形態に係る血中尿酸値改善剤は、血中尿酸値制御剤、血中尿酸値上昇抑制剤、血中尿酸値低下剤ということもできる。 The blood uric acid level improving agent according to this embodiment contains monoglucosyl hesperidin as an active ingredient. The blood uric acid level improving agent according to the present embodiment can control the blood uric acid level within a normal range or a value close to the normal range. Therefore, the blood uric acid level improving agent according to the present embodiment can also be referred to as a blood uric acid level control agent, a blood uric acid level increase inhibitor, and a blood uric acid level lowering agent.
　なお、公益社団法人日本人間ドック学会によれば、血中尿酸値の基準値は、２．１～７．０ｍｇ／ｄＬ程度とされている。 In addition, according to the Japan Medical Dock Association, the reference value of blood uric acid level is about 2.1 to 7.0 mg / dL.
　モノグルコシルヘスペリジンは、柑橘類に含まれるポリフェノールの１種であるヘスペリジンのルチノース単位中のグルコース残基にα－１，４結合により１つのグルコースが結合した化合物である。 Monoglucosyl hesperidin is a compound in which one glucose is bonded to a glucose residue in a rutinose unit of hesperidin, which is one of polyphenols contained in citrus, by an α-1,4 bond.
　モノグルコシルヘスペリジンは、市販のものを用いてもよく、化学合成によって得られたものを用いてもよく、ヘスペリジンを糖転移酵素（例えば、シクロデキストリングルコシルトランスフェラーゼ）による酵素処理を施すことよって得られたものを用いてもよい。 Monoglucosyl hesperidin may be a commercially available product, or may be obtained by chemical synthesis, and obtained by subjecting hesperidin to an enzyme treatment with a glycosyltransferase (eg, cyclodextrin glucosyltransferase). A thing may be used.
　本実施形態に係る血中尿酸値改善剤は、モノグルコシルヘスペリジンを含む酵素処理ヘスペリジンを有効成分とすることが好ましい。ここで、酵素処理ヘスペリジンとは、既存添加物名簿収載品目リスト（公益財団法人日本食品化学研究振興財団、平成２６年１月３０日改正）に記載されている「酵素処理ヘスペリジン」と同義である。 The blood uric acid level improving agent according to the present embodiment preferably contains enzyme-treated hesperidin containing monoglucosyl hesperidin as an active ingredient. Here, enzyme-treated hesperidin is synonymous with “enzyme-treated hesperidin” described in the list of items in the existing additive list (Japan Food Chemistry Research Foundation, revised on January 30, 2014). .
　酵素処理ヘスペリジンは、ヘスペリジンの酵素処理物であり、ヘスペリジン、α－グルコシルヘスペリジン、７－グルコシルヘスペレチン等のヘスペレチン配糖体を含むものである。ここで、α－グルコシルヘスペリジンとは、ヘスペリジンのルチノース単位中のグルコース残基にα－１，４結合により１つ以上のグルコースが結合した化合物（糖転移ヘスペリジン）であり、モノグルコシルヘスペリジンを含むものである。 Enzyme-treated hesperidin is an enzyme-treated product of hesperidin and contains hesperetin glycosides such as hesperidin, α-glucosyl hesperidin, and 7-glucosyl hesperetin. Here, α-glucosyl hesperidin is a compound (glycosylated hesperidin) in which one or more glucose is bonded to a glucose residue in the rutinose unit of hesperidin by α-1,4 bond, and includes monoglucosyl hesperidin. .
　本実施形態に係る酵素処理ヘスペリジンはモノグルコシルヘスペリジンを含む。上記酵素処理ヘスペリジンにおけるモノグルコシルヘスペリジンの含有率は、酵素処理ヘスペリジン全量を基準として、５０～９５ｗ／ｗ％であってよく、好ましくは６０～９０ｗ／ｗ％であってよく、より好ましくは７５～８５ｗ／ｗ％であってよい。上記レモン抽出物の酵素処理物におけるモノグルコシルヘスペリジン含有率が上記範囲であることにより、血中尿酸値改善作用がより一層優れたものとなる。 The enzyme-treated hesperidin according to this embodiment includes monoglucosyl hesperidin. The content of monoglucosyl hesperidin in the enzyme-treated hesperidin may be 50 to 95 w / w%, preferably 60 to 90 w / w%, more preferably 75 to 95% based on the total amount of enzyme-treated hesperidin. It may be 85 w / w%. When the monoglucosyl hesperidin content in the enzyme-treated product of the lemon extract is within the above range, the blood uric acid level improving effect is further improved.
　酵素処理ヘスペリジンをヘスペリジンから酵素処理により得る場合、ヘスペリジンは、柑橘類からの抽出によって得られたものを用いてもよく、市販のものを用いてもよく、化学合成によって得られたものを用いてもよいが、柑橘類からの抽出によって得られたものを用いることが好ましい。 When enzyme-treated hesperidin is obtained from hesperidin by enzymatic treatment, hesperidin may be one obtained by extraction from citrus fruits, one commercially available, or one obtained by chemical synthesis. Although it is good, it is preferable to use what was obtained by extraction from citrus fruits.
　上記柑橘類としては、例えば、レモン、みかん、ライム等が挙げられる。これらの柑橘類は１種を単独で使用しても、２種以上を組み合わせて使用してもよい。上記柑橘類は、レモンであることが好ましい。これにより、抽出原料に由来する臭気が低臭気となるため香味に優れたものとなる。 Examples of the citrus fruits include lemon, mandarin orange and lime. These citrus fruits may be used alone or in combination of two or more. The citrus fruits are preferably lemons. Thereby, since the odor derived from the extraction raw material becomes a low odor, it becomes excellent in flavor.
　温州みかん、ダイダイ由来のヘスペリジン抽出物の酵素処理ヘスペリジンとしては、例えば、東洋精糖（株）製の商品「αＧヘスペリジンＰＳ」、「αＧヘスペリジンＰＡ－Ｔ」が挙げられる。「αＧヘスペリジンＰＳ」には、モノグルコシルヘスペリジン８５質量％、ヘスペリジン１質量％、７－グルコシルヘスペレチン１０質量％が含まれおり、ヘスペレチンは含まれていない。「αＧヘスペリジンＰＡ－Ｔ」には、モノグルコシルヘスペリジン８５質量％、ヘスペリジン１０質量％が含まれており、７－グルコシルヘスペレチンおよびヘスペレチンは含まれていない。 Examples of the enzyme-treated hesperidin of an extract of hesperidin derived from mandarin orange and Daidai include “αG Hesperidin PS” and “αG Hesperidin PA-T” manufactured by Toyo Seika Co., Ltd. “ΑG Hesperidin PS” contains 85% by mass of monoglucosyl hesperidin, 1% by mass of hesperidin, and 10% by mass of 7-glucosyl hesperetin, and does not contain hesperetin. “ΑG Hesperidin PA-T” contains 85% by mass of monoglucosyl hesperidin and 10% by mass of hesperidin, and does not contain 7-glucosyl hesperetin and hesperetin.
　レモン由来のヘスペリジン抽出物の酵素処理ヘスペリジンとしては、例えば、特開２００５－３４３８６５号公報に記載の方法に準じて製造することもできる。 As the enzyme-treated hesperidin of the lemon-derived hesperidin extract, for example, it can also be produced according to the method described in JP-A-2005-343865.
　レモンとしては、グリーンレモンであることが好ましい。グリーンレモンとは、収穫時におけるレモンの果皮が緑色の状態であるレモン、いわゆるレモンの幼果を意味する。 The lemon is preferably green lemon. The green lemon means a lemon in which the peel of the lemon at the time of harvest is in a green state, so-called lemon fruit.
　レモンからの抽出に用いる原料（抽出原料）は、レモンの果実又はその構成成分が使用される。果実の構成成分としては、果皮、果汁、じょうのう膜、さのう及び種子が挙げられる。果実又はその構成成分のうち、ヘスペリジンを多量に得ることが容易である点から、抽出原料として、果皮を用いることが好ましい。上記抽出原料は、乾燥、凍結、加工、粉砕、選別等の処理が施されたものであってもよい。 The raw material (extraction raw material) used for extraction from lemon is lemon fruit or its constituents. Examples of the constituent components of fruits include fruit skin, fruit juice, scabbard, potato and seeds. From the viewpoint of easily obtaining a large amount of hesperidin among fruits or constituents thereof, it is preferable to use a peel as an extraction raw material. The extraction raw material may be subjected to processing such as drying, freezing, processing, pulverization, and selection.
　レモンからの抽出は、レモンを溶媒に浸漬し、これを濾過することによって行うことができる。溶媒としては、例えば、水、水酸化ナトリウム水溶液等のアルカリ水溶液、エタノール等のアルコール等を用いることができる。溶媒は、１種を単独で使用しても、２種以上を組み合わせて使用してもよい。 Extraction from lemon can be performed by immersing lemon in a solvent and filtering it. As the solvent, for example, water, an alkaline aqueous solution such as an aqueous sodium hydroxide solution, an alcohol such as ethanol, or the like can be used. A solvent may be used individually by 1 type, or may be used in combination of 2 or more type.
　ヘスペリジンを含むレモン抽出物は、例えば、レモンをアルカリ水溶液（例えば、水酸化ナトリウム水溶液）に浸漬し、これを濾過し、酸性条件下で析出させることにより得ることができる。 The lemon extract containing hesperidin can be obtained, for example, by immersing the lemon in an alkaline aqueous solution (for example, an aqueous sodium hydroxide solution), filtering it, and precipitating it under acidic conditions.
　酵素処理ヘスペリジンは、ヘスペリジン含有物をデンプン、デキストリン、オリゴ糖等の糖付与体の存在下でシクロデキストリングルカノトランスフェラーゼ等の糖転移酵素に作用させた後、多孔性合成吸着樹脂、イオン交換樹脂、及びカーボン処理等による処理に供することでヘスペリジンの酵素処理物として得ることができる。上記酵素処理物は更に、他の酵素（例えば、グルコアミラーゼ等の糖加水分解酵素）により処理されたものであってもよく、クロマト分離装置等を用いて精製・分取されたものであってもよい。 Enzyme-treated hesperidin is a porous synthetic adsorption resin, ion-exchange resin, after allowing hesperidin-containing material to act on a glycosyltransferase such as cyclodextrin glucanotransferase in the presence of a sugar donor such as starch, dextrin or oligosaccharide. And it can be obtained as an enzyme-treated product of hesperidin by subjecting it to a treatment such as carbon treatment. The enzyme-treated product may be further treated with another enzyme (for example, a sugar hydrolase such as glucoamylase), and is purified and separated using a chromatographic separation apparatus or the like. Also good.
　本実施形態に係る血中尿酸値改善剤において、上記酵素処理ヘスペリジンはレモン抽出物の酵素処理物であることが好ましい。これにより、抽出原料に由来する臭気が低臭気となるため香味に優れたものとなる。上記レモン抽出物は、グリーンレモン抽出物であることが好ましい。 In the blood uric acid level improving agent according to this embodiment, the enzyme-treated hesperidin is preferably an enzyme-treated product of a lemon extract. Thereby, since the odor derived from the extraction raw material becomes a low odor, it becomes excellent in flavor. The lemon extract is preferably a green lemon extract.
　モノグルコシルヘスペリジン及び酵素処理ヘスペリジンの分析は、公知の方法（例えば、第８版食品添加物公定書（厚生労働省）に記載の条件によるＨＰＬＣ）を用いて行うことができる。 The analysis of monoglucosyl hesperidin and enzyme-treated hesperidin can be performed using a known method (for example, HPLC under the conditions described in the 8th edition Food Additives Official Document (Ministry of Health, Labor and Welfare).
　本実施形態に係る血中尿酸値改善剤は、モノグルコシルヘスペリジンを有効成分とするため、摂取することによって、血中尿酸値を改善することができる。また、血中尿酸値濃度が高い状態が持続すると痛風の原因となるが、血中尿酸値濃度を改善することによって、痛風を予防することができる。したがって上記血中尿酸値改善剤は、痛風発症及び再発の予防のために用いることができる。 Since the blood uric acid level improving agent according to this embodiment contains monoglucosyl hesperidin as an active ingredient, the blood uric acid level can be improved by ingestion. Further, if a state in which the blood uric acid value concentration is high continues, it causes gout, but gout can be prevented by improving the blood uric acid value concentration. Therefore, the blood uric acid level improving agent can be used for preventing gout onset and recurrence.
　本実施形態に係る血中尿酸値改善剤は、固体（例えば、粉末）、液体（水溶性又は脂溶性の溶液又は懸濁液）、ペースト等のいずれの形状でもよく、また、散剤、顆粒剤、錠剤、カプセル剤、液剤、懸濁剤、乳剤、軟膏剤、硬膏剤等のいずれの剤形をとってもよい。また、放出制御製剤の形態をとることもできる。 The blood uric acid level improving agent according to the present embodiment may be in any shape such as a solid (for example, a powder), a liquid (a water-soluble or fat-soluble solution or suspension), a paste, or the like. , Tablets, capsules, solutions, suspensions, emulsions, ointments, plasters and the like. It can also take the form of a controlled release formulation.
　本実施形態に係る血中尿酸値改善剤は、ヒトに投与（摂取）されても、非ヒト哺乳動物に投与されてもよい。本実施形態に係る血中尿酸値改善剤の投与量（摂取量）は、モノグルコシルヘスペリジンを基準として、１日あたり例えば１０ｍｇ～１０００ｍｇであってよく、好ましくは５０ｍｇ～８００ｍｇであり、より好ましくは、１００ｍｇ～６００ｍｇである。 The blood uric acid level improving agent according to this embodiment may be administered (ingested) to humans or administered to non-human mammals. The dose (intake) of the blood uric acid level improving agent according to the present embodiment may be, for example, 10 mg to 1000 mg per day, preferably 50 mg to 800 mg, more preferably, based on monoglucosyl hesperidin. , 100 mg to 600 mg.
　本実施形態に係る血中尿酸値改善剤は、経口投与されてもよく、非経口投与されてもよいが、経口投与されることが好ましい。血中尿酸値改善剤は、１日あたりの投与量が上記範囲内にあれば、１日１回投与されてもよく、１日複数回に分けて投与されてもよい。 The blood uric acid level improving agent according to this embodiment may be administered orally or parenterally, but is preferably administered orally. The blood uric acid level-improving agent may be administered once a day, or may be administered in a plurality of times a day as long as the dose per day is within the above range.
　本実施形態に係る血中尿酸値改善剤は、一過性の血中尿酸値改善に限らず、長期投与による血中尿酸値改善に用いることができる。ここで、長期投与とは、８日以上の期間にわたって継続して投与（摂取）されることを意味する。 The blood uric acid level improving agent according to this embodiment can be used not only for transient blood uric acid level improvement but also for blood uric acid level improvement by long-term administration. Here, long-term administration means continuous administration (ingestion) over a period of 8 days or more.
　本実施形態に係る血中尿酸値改善剤は、長期投与用に好適に用いることができる。上記血中尿酸値改善剤は、長期投与によって、血中尿酸値改善効果がより一層顕著なものとなる。本実施形態に係る血中尿酸値改善剤は、８日以上の期間にわたり投与されることが好ましく、２週間以上の期間にわたり投与されることがより好ましく、４週間以上の期間にわたり投与されることが更に好ましい。 The blood uric acid level improving agent according to this embodiment can be suitably used for long-term administration. The blood uric acid level improving agent becomes more prominent in blood uric acid level improving effect by long-term administration. The blood uric acid level improving agent according to this embodiment is preferably administered over a period of 8 days or more, more preferably administered over a period of 2 weeks or more, and administration over a period of 4 weeks or more. Is more preferable.
　本実施形態に係る血中尿酸値改善剤は、医薬品、医薬部外品、飲食品（飲料、食品）、飲食品添加物、飼料、飼料添加物等の製品の成分として使用することができる。 The blood uric acid level improving agent according to the present embodiment can be used as a component of products such as pharmaceuticals, quasi drugs, food and drink (beverages and foods), food and drink additives, feed and feed additives.
　本実施形態に係る血中尿酸値改善剤からなる、又は血中尿酸値改善剤を含む上記製品は、血中尿酸値改善用であってよく、血中尿酸値制御用であってよく、血中尿酸値上昇抑制用であってよく、血中尿酸値低下用であってよく、血中尿酸値維持用であってよい。また、上記製品には、血中尿酸値を改善する、血中尿酸値を制御する、血中尿酸値の上昇を抑制する、血中尿酸値を低下させる、血中尿酸値を適正化する、食事のプリン体が気になる方へ、お酒やおいしいものが好きな方へ等の表示が付されていてもよい。 The product comprising the blood uric acid level improving agent according to the present embodiment or containing the blood uric acid level improving agent may be for blood uric acid level improvement, for blood uric acid level control, blood It may be for suppressing the increase in the middle uric acid level, for lowering the blood uric acid level, or for maintaining the blood uric acid level. In addition, the above products improve blood uric acid level, control blood uric acid level, suppress blood uric acid level rise, reduce blood uric acid level, optimize blood uric acid level, For those who are concerned about the pudding of food, those who like liquor and delicious food may be displayed.
　本実施形態に係る血中尿酸値改善用飲食品は、モノグルコシルヘスペリジンを有効成分とする。これにより、血中尿酸値を改善することができる。 The food and drink for improving blood uric acid level according to this embodiment contains monoglucosyl hesperidin as an active ingredient. Thereby, the blood uric acid level can be improved.
　本実施形態に係る血中尿酸値改善用飲食品において、上記酵素処理ヘスペリジンはレモン抽出物の酵素処理物であることが好ましい。これにより、抽出原料に由来する臭気が低臭気となるため香味に優れたものとなる。上記レモン抽出物は、グリーンレモン抽出物であることが好ましい。 In the food and drink for improving blood uric acid level according to this embodiment, the enzyme-treated hesperidin is preferably an enzyme-treated product of lemon extract. Thereby, since the odor derived from the extraction raw material becomes a low odor, it becomes excellent in flavor. The lemon extract is preferably a green lemon extract.
　本実施形態に係る血中尿酸値改善用飲食品の摂取量は、モノグルコシルヘスペリジンを基準として、１日あたり例えば１０ｍｇ～１０００ｍｇであってよく、好ましくは５０ｍｇ～８００ｍｇであり、より好ましくは、１００ｍｇ～６００ｍｇである。 The intake of the food for improving blood uric acid level according to this embodiment may be, for example, 10 mg to 1000 mg per day, preferably 50 mg to 800 mg, more preferably 100 mg, based on monoglucosyl hesperidin. ~ 600 mg.
　本実施形態に係る血中尿酸値改善用飲食品の摂取量は、上記酵素処理ヘスペリジンを基準として、１日あたり例えば１３ｍｇ～１３００ｍｇであってよく、好ましくは６５ｍｇ～１０４０ｍｇであり、より好ましくは、１３０ｍｇ～７８０ｍｇである。 The intake of the food and beverage for improving blood uric acid level according to this embodiment may be, for example, 13 mg to 1300 mg per day, preferably 65 mg to 1040 mg, more preferably, based on the enzyme-treated hesperidin. 130 mg to 780 mg.
　上記血中尿酸値改善用飲食品は、血中尿酸値改善用飲料及び血中尿酸値改善用食品を含む。本実施形態に係る血中尿酸値改善用飲食品は、一過性の血中尿酸値改善に限らず、長期投与による血中尿酸値改善に用いることができる。 The above-mentioned food and drink for improving blood uric acid level include beverages for improving blood uric acid level and foods for improving blood uric acid level. The food / beverage product for improving blood uric acid level according to the present embodiment is not limited to transient blood uric acid level improvement, but can be used for blood uric acid level improvement by long-term administration.
　上記血中尿酸値改善用飲料としては、例えば、清涼飲料、果汁飲料、乳飲料、炭酸飲料、アルコール飲料、ノンアルコール飲料、ビールテイスト飲料、スポーツドリンク、栄養ドリンク等が挙げられる。 Examples of the beverage for improving blood uric acid level include soft drinks, fruit juice drinks, milk drinks, carbonated drinks, alcoholic drinks, non-alcoholic drinks, beer-taste drinks, sports drinks, and nutrition drinks.
　上記血中尿酸値改善用食品としては、パン類、麺類、米類、豆腐、乳製品、醤油、味噌、菓子類、サプリメント剤等が挙げられる。また、健康食品、機能性表示食品、特別用途食品、栄養補助食品、サプリメント又は特定保健用食品等の関与成分として使用することもできる。 Examples of the food for improving blood uric acid level include breads, noodles, rice, tofu, dairy products, soy sauce, miso, confectionery, and supplements. It can also be used as an ingredient involved in health foods, functional labeling foods, special-purpose foods, dietary supplements, supplements or foods for specified health use.
　本実施形態に係る血中尿酸値改善用飲食品は、本発明の効果を損なわない範囲において、その他の成分（添加剤）を含有してもよい。その他の成分としては、例えば、甘味料、香料、酸味料、着色料、酸化防止剤、調味料、ビタミン類、ミネラル類、ｐＨ調整剤、安定剤、ゲル化剤、食物繊維、並びに難消化性デキストリン等を使用することができる。これらの成分は１種を単独で、又は２種以上を組み合わせて使用することができる。 The food and drink for improving blood uric acid level according to this embodiment may contain other components (additives) as long as the effects of the present invention are not impaired. Other ingredients include, for example, sweeteners, flavorings, acidulants, colorants, antioxidants, seasonings, vitamins, minerals, pH adjusters, stabilizers, gelling agents, dietary fiber, and indigestible Dextrin and the like can be used. These components can be used individually by 1 type or in combination of 2 or more types.
　甘味料としては、砂糖、三温糖、黒糖、はちみつ、還元澱粉糖化物、オリゴ糖、糖アルコール、希少糖等の糖質、スクラロース、アスパルテーム、アセスルファムカリウム、サッカリン、アリテーム、ネオテーム等の高甘味度甘味料等を使用することができる。これらの甘味料は１種を単独で、又は２種以上を組み合わせて使用することができる。 Sweeteners include sugar, tri-sugar, brown sugar, honey, reduced starch saccharified, oligosaccharides, sugar alcohols, sugars such as rare sugars, sucralose, aspartame, acesulfame potassium, saccharin, alitame, neotame, etc. Sweeteners and the like can be used. These sweeteners can be used alone or in combination of two or more.
　香料としては、天然物、合成物のいずれの香料であっても使用することができる。香料としては、特に限定されるものではないが、例えば、柑橘フレーバー等を使用することができる。これらの香料は１種を単独で、又は２種以上を組み合わせて使用することができる。 As the fragrance, any natural or synthetic fragrance can be used. Although it does not specifically limit as a fragrance | flavor, For example, a citrus flavor etc. can be used. These fragrance | flavors can be used individually by 1 type or in combination of 2 or more types.
　酸味料は、飲食品に使用するものであれば特に限定されずに使用することができる。酸味料としては、例えば、クエン酸、乳酸、リンゴ酸、リン酸、コハク酸、酒石酸、酢酸等を使用することができる。これらの酸味料は１種を単独で、又は２種以上を組み合わせて使用することができる。 The sour agent can be used without particular limitation as long as it is used for food and drink. As the acidulant, for example, citric acid, lactic acid, malic acid, phosphoric acid, succinic acid, tartaric acid, acetic acid and the like can be used. These acidulants can be used alone or in combination of two or more.
　着色料としては、飲食品の色付けに用いるものであれば、天然着色料、及び合成着色料のいずれも使用できる。着色料としては、例えば、カラメル色素、クチナシ色素、マリーゴールド色素、カロテン色素、アントシアニン色素、果汁色素、野菜色素、合成色素等を使用することができる。これらの色素は１種を単独で、又は２種以上を組み合わせて使用することができる。 As the coloring agent, any natural coloring agent or synthetic coloring agent can be used as long as it is used for coloring food and drink. As the colorant, for example, caramel color, gardenia color, marigold color, carotene color, anthocyanin color, fruit juice color, vegetable color, synthetic color and the like can be used. These pigment | dyes can be used individually by 1 type or in combination of 2 or more types.
　本実施形態に係る血中尿酸値改善用飲食品は、容器詰め飲食品とすることもできる。容器詰め飲食品とする場合の容器としては、一般の飲食品と同様に、例えば、ガラス瓶、樹脂製成形容器、金属缶、金属箔又はプラスチィックフィルムと複合された紙容器等を用いることができる。容器の種類、形状及び色彩は特に制限されるものではない。 The food and drink for improving blood uric acid level according to this embodiment may be a container-packed food and drink. As a container in the case of a container-packed food or drink, for example, a glass bottle, a resin molded container, a metal can, a metal foil, a paper container combined with a plastic film, or the like can be used, as in a general food or drink. The type, shape and color of the container are not particularly limited.
　樹脂製成形容器を構成する樹脂としては、例えば、ポリエチレンテレフタレート、ポリブチレンテレフタレート等のポリエステル樹脂、ポリエチレン、ポリプロピレン、ポリブチレン等のポリオレフィン等が挙げられる。これらの樹脂の重量平均分子量、結晶化度等は、特に制限されるものではなく、飲食品の流通条件、保管条件等に合わせて、適宜選択することが可能である。なお、ポリエチレンテレフタレートを使用した樹脂製成形容器は、一般にペットボトルと称される。ペットボトルとしては、飲食品の常温充填（アセプチック充填）を想定したアセプチック用ペットボトル、加温殺菌を行いながら飲食品を充填すること、又は加温販売を想定した耐熱ペットボトルなどに分類されるが、本実施形態においては、いずれも使用可能である。 Examples of the resin constituting the resin-molded container include polyester resins such as polyethylene terephthalate and polybutylene terephthalate, and polyolefins such as polyethylene, polypropylene, and polybutylene. The weight average molecular weight, crystallinity, and the like of these resins are not particularly limited, and can be appropriately selected according to the distribution conditions, storage conditions, and the like of the food and drink. A resin-made container using polyethylene terephthalate is generally called a PET bottle. PET bottles are classified into aseptic PET bottles assuming normal temperature filling (aseptic filling) of foods and drinks, filling foods and drinks while performing heat sterilization, or heat-resistant PET bottles assuming hot sales. However, any of them can be used in the present embodiment.
　金属缶としては、例えば、スチール缶、アルミ缶、ブリキ缶等が挙げられる。 Examples of metal cans include steel cans, aluminum cans and tin cans.
　本実施形態に係る血中尿酸値改善用飲食品を容器詰め飲食品とする場合、必要に応じて殺菌処理を行ってもよい。容器詰め飲食品とする場合の殺菌及び容器充填は、例えば、金属缶に充填後、食品衛生法に定められた条件での加熱殺菌が例示される。ＰＥＴボトル、紙容器のようにレトルト殺菌できないものについては、あらかじめ上記と同等の殺菌条件、例えばプレート式熱交換器等で高温短時間殺菌後、一定の温度まで冷却して容器に充填する等の方法が例示される。 </ RTI> When the food / beverage for improving blood uric acid level according to the present embodiment is used as a container-packed food / beverage, sterilization may be performed as necessary. Examples of the sterilization and container filling in the case of a container-packed food / beverage product include heat sterilization under conditions defined in the Food Sanitation Law after filling a metal can. For PET bottles and paper containers that cannot be sterilized by retort, sterilize under the same conditions as above, for example, after sterilizing at high temperature and short time with a plate heat exchanger, etc. A method is illustrated.
　本発明の一実施形態として、モノグルコシルヘスペリジンを、それを必要とする対象に投与することを含む、血中尿酸値の改善方法が提供される。また、本発明の一実施形態として、血中尿酸値改善剤の製造のための、モノグルコシルヘスペリジンの使用が提供される。更に、本発明の一実施形態として、血中尿酸値の改善に使用するための、モノグルコシルヘスペリジンが提供される。これらの実施形態における、投与方法、投与対象、投与量等については、上記の血中尿酸値改善剤におけるものと同様であってよい。 As one embodiment of the present invention, there is provided a method for improving blood uric acid level, comprising administering monoglucosyl hesperidin to a subject in need thereof. Moreover, use of monoglucosyl hesperidin for manufacture of a blood uric acid level improving agent is provided as one Embodiment of this invention. Furthermore, as one embodiment of the present invention, monoglucosyl hesperidin for use in improving blood uric acid levels is provided. In these embodiments, the administration method, administration subject, dosage and the like may be the same as those in the blood uric acid level improving agent.
　以下、実施例に基づいて本発明をより具体的に説明する。ただし、本発明は、以下の実施例により限定されるものではない。 Hereinafter, the present invention will be described more specifically based on examples. However, the present invention is not limited to the following examples.
（試験試料の調製）
　グリーンレモン抽出物の酵素処理物は、特開２００５－３４３８６５号公報に記載の方法に準じて調製した。具体的な調製法については下記のとおりである。 (Preparation of test sample)
An enzyme-treated product of green lemon extract was prepared according to the method described in JP-A-2005-343865. The specific preparation method is as follows.
　グリーンレモン果皮１重量部当たりに水１０重量部の量で加え、さらにアルカリ（苛性ソ－ダ）を加えてｐＨ１２のアルカリ液に調整した後、５０℃で２時間攪拌しながら抽出を行った。ろ過により残渣を除去した後、塩酸でｐＨ３．０に下げヘスペリジンを析出させた後、固液分離、乾燥してヘスペリジン含有物を得た。 After adding 10 parts by weight of water per 1 part by weight of green lemon peel and further adding an alkali (caustic soda) to adjust to an alkaline solution having a pH of 12, extraction was performed with stirring at 50 ° C. for 2 hours. After removing the residue by filtration, the pH was lowered to 3.0 with hydrochloric acid to precipitate hesperidin, followed by solid-liquid separation and drying to obtain a hesperidin-containing product.
　このヘスペリジン含有物１重量部に水５０００重量部を加え、常圧下、温度８０℃で３０分間加熱処理を行った。次に、得られたスラリーをアルカリ溶解した後、デキストリン（ＤＥ２０、松谷化学工業株式会社社製）６重量部を加え加熱溶解させ、これにシクロデキストリングルカノトランスフェラ－ゼ（Ｔｏｒｕｚｙｍｅ、Ｎｏｖｏｚｙｍｅｓ社製）をデキストリン１ｇ当たり３０単位加え、ｐＨ　６．０、７０℃に維持して１８時間反応させ、反応液を得た。 5,000 parts by weight of water was added to 1 part by weight of this hesperidin-containing material, and a heat treatment was performed at 80 ° C. for 30 minutes under normal pressure. Next, the obtained slurry was dissolved in an alkali, 6 parts by weight of dextrin (DE20, manufactured by Matsutani Chemical Co., Ltd.) was added and dissolved by heating, and cyclodextrin glucanotransferase (Toruzyme, manufactured by Novozymes) was added thereto. ) Was added at 30 units per gram of dextrin and reacted at pH 6.0 and 70 ° C. for 18 hours to obtain a reaction solution.
　この反応液を多孔性合成樹脂吸着剤（商品名「ＨＰ－１０」、三菱化成社製）が充填されたカラムにＳＶ２．０で通液し、酵素処理ヘスペリジンを吸着させた。次に、このカラムを水で洗浄しデキストリン分解物、臭い物質を洗浄・除去した後、５０ｖ／ｖ％エタノ－ル水溶液を通液し酵素処理ヘスペリジンなどを脱着した。得られた脱着液を濃縮して溶出液中のエタノールを留去し、乾燥粉末を得た。 The reaction solution was passed through a column packed with a porous synthetic resin adsorbent (trade name “HP-10”, manufactured by Mitsubishi Kasei Co., Ltd.) at SV 2.0 to adsorb enzyme-treated hesperidin. Next, this column was washed with water to wash and remove dextrin decomposition products and odorous substances, and then passed through a 50 v / v% aqueous ethanol solution to desorb enzyme-treated hesperidin and the like. The obtained desorption solution was concentrated to remove ethanol in the eluate to obtain a dry powder.
　得られた乾燥粉末１重量部にイオン交換水１０重量部を加えて温度６０℃に加熱し、含まれる固形分を溶解させた後、約３０℃に冷却して強酸性陽イオン交換樹脂（商品名「ダイアイオンＳＫ１Ｂ」、三菱化成社製）と強塩基性イオン交換樹脂（商品名「ダイアイオンＳＡ１０Ａ」、三菱化成社製）に接触させて脱塩、脱臭、脱色を行った。 10 parts by weight of ion-exchanged water is added to 1 part by weight of the obtained dry powder and heated to a temperature of 60 ° C. to dissolve the contained solids, and then cooled to about 30 ° C. to strongly acidic cation exchange resin Desalination, deodorization and decolorization were carried out by contacting with a name “Diaion SK1B” (manufactured by Mitsubishi Kasei) and a strongly basic ion exchange resin (trade name “Diaion SA10A”, manufactured by Mitsubishi Kasei).
　得られた流出液に粉末活性炭（商品名「精製白鷺」、武田食品工業社製）０．０１重量部を添加し、６０℃で１時間攪拌した。次に、ろ過により粉末活性炭を除去した後、濃縮・乾燥し、酵素処理ヘスペリジンとして粉末状のグリーンレモン抽出物の酵素処理物（以下、「ＧＬＰＰ」とも称する）を得た。 0.01 parts by weight of powdered activated carbon (trade name “Purified Shirakaba”, manufactured by Takeda Food Industry Co., Ltd.) was added to the obtained effluent and stirred at 60 ° C. for 1 hour. Next, the powdered activated carbon was removed by filtration, followed by concentration and drying to obtain a powdered green lemon extract enzyme-treated product (hereinafter also referred to as “GLPP”) as enzyme-treated hesperidin.
　得られたＧＬＰＰに含まれるモノグルコシルヘスペリジン及びヘスペリジンをＨＰＬＣにより分析した。表１にＧＬＰＰの成分組成を示す。 Monoglucosyl hesperidin and hesperidin contained in the obtained GLPP were analyzed by HPLC. Table 1 shows the component composition of GLPP.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　表１に示すとおり、ＧＬＰＰはモノグルコシルヘスペリジンを高含有するものである。 As shown in Table 1, GLPP contains a high content of monoglucosyl hesperidin.
［実施例１：急性試験］
　ＳＤラット（雄性、５週齢）を温度２３±１℃、湿度５５％の飼育条件で、ＣＲＦ－１飼料（オリエンタル酵母社製）及び水道水を自由摂取条件で１週間馴化飼育した。５匹（ＧＬＰＰ群）にＧＬＰＰを５００ｍｇ／ｋｇ経口投与し、ＧＬＰＰ投与後２時間経過時にオキソン酸を２５０ｍｇ／ｋｇ腹腔内投与し、経時的な血中尿酸値の変化を調べた。また、ＧＬＰＰ非投与であること以外は上記同様にして、対照群についても同量の滅菌生理食塩水を経口投与し、経時的な血中尿酸値の変化を調べた。血中尿酸値は、オキソン酸投与時点を基準（０時間）として、０、１、２、４時間経過時に測定し、測定試料はラット尾静脈より採血して得た。また、血中尿酸値の変化率はオキソン酸投与から２時間前（ＧＬＰＰ群においてはＧＬＰＰ投与時点）における各個体の血中尿酸値（１．０）を基準として、算出した。 [Example 1: Acute test]
SD rats (male, 5 weeks old) were bred for 1 week under free feeding conditions of CRF-1 feed (Oriental Yeast Co., Ltd.) and tap water under the breeding conditions of a temperature of 23 ± 1 ° C. and a humidity of 55%. Five animals (GLPP group) were orally administered GLPP at 500 mg / kg, and oxonic acid was administered intraperitoneally at 250 mg / kg 2 hours after GLPP administration, and changes in blood uric acid levels over time were examined. Further, in the same manner as described above except that GLPP was not administered, the same amount of sterile physiological saline was orally administered to the control group, and the change in blood uric acid level over time was examined. The blood uric acid level was measured at 0, 1, 2, and 4 hours with reference to the time point of administration of oxonic acid (0 hour), and the measurement sample was obtained by collecting blood from the rat tail vein. Moreover, the change rate of the blood uric acid level was calculated based on the blood uric acid level (1.0) of each individual 2 hours before the oxonic acid administration (in the GLPP group, at the time of GLPP administration).
　なお、げっ歯類はヒトと異なり、プリン体代謝経路で合成された尿酸は速やかにウリカーゼという酵素によりアラントインに代謝されるため、血清尿酸値は通常低く保たれている。そこで、ウリカーゼ阻害薬であるオキソン酸によって尿酸代謝を抑制したラットを高尿酸血症モデルラットとして用いた。 Note that unlike rodents in humans, uric acid synthesized in the purine metabolism pathway is rapidly metabolized to allantoin by an enzyme called uricase, and thus the serum uric acid level is usually kept low. Therefore, a rat in which uric acid metabolism was suppressed by oxonic acid, a uricase inhibitor, was used as a hyperuricemia model rat.
　血中尿酸値の測定は以下の方法により行った。すなわち、測定する血清１０μＬに蒸留水９０μＬを加えて希釈した後、１０％トリクロロ酢酸／水２０μＬを更に加えて除タンパク質処理し、混和後、ボルテックスした試料を氷上で３０分間静置し、遠心分離（１５，０００ｒｐｍ、１０ｍｉｎ、４℃）した。得られた上清を０．４５μｍフィルター濾過して下記条件でＬＣ－ＭＳ／ＭＳ分析に供した。標品は尿酸（和光純薬工業社製）を用いた。 The blood uric acid level was measured by the following method. Specifically, 90 μL of distilled water was added to 10 μL of the serum to be measured, diluted, and further 20 μL of 10% trichloroacetic acid / water was added to remove protein. After mixing, the vortexed sample was allowed to stand on ice for 30 minutes and centrifuged. (15,000 rpm, 10 min, 4 ° C.). The obtained supernatant was filtered through a 0.45 μm filter and subjected to LC-MS / MS analysis under the following conditions. As a sample, uric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was used.
＜ＨＰＬＣ＞
カラム：Ｓｙｍｍｅｔｒｙ　Ｓｈｉｅｌｄ　ＲＰ１８、３．５μｍ、１５０ｍｍ×２．１ｍｍｉ．ｄ．（Ｗａｔｅｒｓ社製）
ＨＰＬＣシステム：Ａｇｉｌｅｎｔ　１１００（Ａｇｉｌｅｎｔ　ｔｅｃｈｎｏｌｏｇｉｅｓ社製）
注入量：５μｌ
溶媒：Ａ，１０ｍＭギ酸アンモニウム水溶液＋０．１％ギ酸；Ｂ，ＭｅＣＮ
流速：０．５ｍｌ／ｍｉｎ
溶離液：Ｂ　０％（０．００→２．００ｍｉｎ）－４０％（４．００ｍｉｎ）－４０％（４．０１→６．００ｍｉｎ）－０％（６．０１→１２．００ｍｉｎ）
平衡化：６ｍｉｎ
カラム温度：４０℃
＜検出＞
ＭＳシステム：３２００Ｑｔｒａｐ（ＡＢ　ＳＣＩＥＸ社製）
イオン化：ＥＳＩ　ｎｅｇａｔｉｖｅ
Ｓｃａｎ　Ｔｙｐｅ：ＭＲＭ（Ｑ１：ｍ／ｚ＝１６７．１、Ｑ３：ｍ／ｚ＝１２４．１）
Ｓｏｕｒｃｅ／Ｇａｓ：ＣＵＲ　２０，ＣＡＤ　４，ＩＳ－４５００、ＴＥＭ６００、ＧＳ１　５０、ＧＳ２　８０
Ｃｏｍｐｏｕｎｄ：ＤＰ－３０、ＥＰ－１０、ＣＥ－２５、ＣＸＰ－４ <HPLC>
Column: Symmetry Shield RP18, 3.5 μm, 150 mm × 2.1 mmi. d. (Waters)
HPLC system: Agilent 1100 (manufactured by Agilent technologies)
Injection volume: 5 μl
Solvent: A, 10 mM aqueous ammonium formate + 0.1% formic acid; B, MeCN
Flow rate: 0.5 ml / min
Eluent: B 0% (0.00 → 2.00 min) -40% (4.00 min) -40% (4.01 → 6.00 min) -0% (6.01 → 12.00 min)
Equilibration: 6 min
Column temperature: 40 ° C
<Detection>
MS system: 3200Qtrap (manufactured by AB SCIEX)
Ionization: ESI negative
Scan Type: MRM (Q1: m / z = 167.1, Q3: m / z = 14.1)
Source / Gas: CUR 20, CAD 4, IS-4500, TEM600, GS1 50, GS2 80
Compound: DP-30, EP-10, CE-25, CXP-4
　図１に尿酸値測定結果の変化率を示す。グラフの値は、各群における尿酸値変化率の平均値を表し、エラーバーはその標準誤差を表す。 Fig. 1 shows the rate of change of uric acid value measurement results. The value of the graph represents the average value of the uric acid value change rate in each group, and the error bar represents its standard error.
　図１に示すとおり、ラットに尿酸値が上昇する処理を施す前にモノグルコシルヘスペリジンを含むＧＬＰＰを摂取させることで血中尿酸値の上昇が抑制されることが示された。 As shown in FIG. 1, it was shown that the increase in blood uric acid level was suppressed by ingesting GLPP containing monoglucosyl hesperidin before the treatment for increasing the uric acid level in rats.
［実施例２：長期投与試験］
　マウス（７週齢、Ｃ５７ＢＬ／６Ｊマウス、チャールスリバー社）は、１週間の馴化飼育を経た後、８週齢の時点で試験に供した。馴化飼育期間及びその後の試験期間を通して、マウスは、温度２３±１℃、湿度５５％、１２時間明暗サイクルの環境下で飼育した。馴化期間の飼料はＭＦ飼料(オリエンタル酵母社製)を使用し、飼料及び水道水は自由摂取とした。 [Example 2: Long-term administration test]
Mice (7-week-old, C57BL / 6J mice, Charles River) were subjected to testing at the age of 8 weeks after one week of acclimatization. Throughout the acclimatization period and subsequent test periods, the mice were housed in an environment with a temperature of 23 ± 1 ° C., a humidity of 55%, and a 12-hour light-dark cycle. The feed during the acclimatization period was MF feed (Oriental Yeast Co., Ltd.), and feed and tap water were freely consumed.
　馴化飼育期間経過後、試験開始時に尾静脈より採血を行い、試験開始時の血中尿酸値が群間で差の無いように群分けした。その後、高尿酸血症誘導食として６０％フルクトース（特級、和光純薬工業社製）、３％尿酸（和光純薬工業社製）、２％オキソン酸カリウム（シグマアルドリッチ社製）を含むＭＦ飼料を試験飼料として対照群のマウスに与えた。また、ＧＬＰＰ群のマウスには試験飼料に更にＧＬＰＰをそれぞれ０．５％、１．０％混餌した飼料を与えた（１．０％はＮ＝８、０．５％はＮ＝７）。試験飼料を用いず、ＭＦ飼料を与えただけの群を非誘導群とした（Ｎ＝５）。試験期間はプラスチック製イノケージに４匹/ケージで４週間集団飼育した。なお、ＧＬＰＰを０．５％及び１．０％混餌した飼料を与えたＧＬＰＰ群を以下、それぞれ「０．５％ＧＬＰＰ群」及び「１．０％ＧＬＰＰ群」ともいう。 After the acclimatization period, blood was collected from the tail vein at the start of the test, and the blood uric acid level at the start of the test was divided into groups so that there was no difference between the groups. Thereafter, MF feed containing 60% fructose (special grade, manufactured by Wako Pure Chemical Industries, Ltd.), 3% uric acid (produced by Wako Pure Chemical Industries, Ltd.), 2% potassium oxonate (produced by Sigma Aldrich) as a hyperuricemia-inducing diet Was fed to a control group of mice as a test diet. In addition, mice in the GLPP group were further fed with GLPP mixed with 0.5% and 1.0% of the test diet (1.0% for N = 8 and 0.5% for N = 7), respectively. The group which only gave MF feed without using test feed was made into the non-induction group (N = 5). During the test period, 4 animals / cage were raised in plastic in cages for 4 weeks. In addition, the GLPP group fed with a diet mixed with 0.5% and 1.0% GLPP is hereinafter also referred to as “0.5% GLPP group” and “1.0% GLPP group”, respectively.
　試験飼料に含まれる６０％フルクトース食は、肝臓へのインスリンを介さない糖の取り込みを増やし、尿酸の基質であるプリン体合成を促進させる食餌であり、マウスにおいて血清尿酸値を増加させることが報告されている。また、実施例１と同様、ウリカーゼ阻害薬であるオキソン酸カリウムを混餌し、高尿酸血症モデルマウスを作成した。更に３％の尿酸を混餌した。 The 60% fructose diet contained in the test diet is a diet that increases the uptake of glucose without insulin through the liver and promotes the synthesis of purine, a substrate for uric acid, and has been reported to increase serum uric acid levels in mice Has been. Further, as in Example 1, hyperuricemia model mice were prepared by feeding with potassium oxonate, which is a uricase inhibitor. Furthermore, 3% uric acid was mixed.
　週に１回体重測定を行い、２週毎に経時採血を尾静脈より行った。採血した血液はすぐに氷冷し、１時間経った後に遠心分離して血清を得た（分析時まで－２０℃保存）。試験開始直後から４週後にかけて、実施例１と同様の方法により各群のマウスの血中尿酸値を測定した。 Body weight was measured once a week, and blood was collected from the tail vein every 2 weeks. The collected blood was immediately ice-cooled, and after 1 hour, it was centrifuged to obtain serum (stored at −20 ° C. until analysis). From the start of the test to 4 weeks later, the blood uric acid level of each group of mice was measured by the same method as in Example 1.
　図２に血中尿酸値の測定結果を示す。試験開始後０週、２週及び４週における各群マウスの血中尿酸値測定結果を、それぞれ図２（ａ）、図２（ｂ）、図２（ｃ）に示す。グラフの値は、各群における血中尿酸値の平均値を表し、エラーバーはその標準誤差を表す。表中の０．５％及び１％はそれぞれ「０．５％ＧＬＰＰ群」及び「１．０％ＧＬＰＰ群」を示す。 Fig. 2 shows the measurement results of blood uric acid levels. The results of measurement of blood uric acid levels in mice of each group at 0 weeks, 2 weeks and 4 weeks after the start of the test are shown in FIGS. 2 (a), 2 (b) and 2 (c), respectively. The value in the graph represents the average value of blood uric acid in each group, and the error bar represents the standard error. 0.5% and 1% in the table indicate “0.5% GLPP group” and “1.0% GLPP group”, respectively.
　図２に示すとおり、モノグルコシルヘスペリジンを含むＧＬＰＰを摂取させることで血中尿酸値の上昇が抑制されることが示された。すなわち、２週経過時点、４週経過時点ともに０．５％及び１．０％ＧＬＰＰ群においてｔ検定で有意差を確認することができ、有意に長期的な血中尿酸値の上昇が抑制されたことを確認することができた。 As shown in FIG. 2, it was shown that an increase in blood uric acid level was suppressed by ingesting GLPP containing monoglucosyl hesperidin. That is, a significant difference can be confirmed by t-test in the 0.5% and 1.0% GLPP groups at both 2 weeks and 4 weeks, and a significant long-term increase in blood uric acid level is suppressed. I was able to confirm that.
　０．５％及び１．０％ＧＬＰＰ群において、２週経過時点の血中尿酸値の減少率はそれぞれ２７％及び３１％であり、４週経過時点の血中尿酸値の減少率はそれぞれ３５％及び３８％であった。なお、本明細書における血中尿酸値の減少率（％）とは、対照群マウスの血中尿酸値（平均値）とＧＬＰＰ群マウスの血中尿酸値（平均値）との差の、対照群マウスの血中尿酸値（平均値）に対する割合である。 In the 0.5% and 1.0% GLPP groups, the rate of decrease in blood uric acid level after 2 weeks was 27% and 31%, respectively, and the rate of decrease in blood uric acid level after 4 weeks was 35 respectively. % And 38%. In this specification, the rate of decrease in blood uric acid level (%) is the difference between the blood uric acid level (average value) of the control group mice and the blood uric acid level (average value) of the GLPP group mice. It is the ratio to the blood uric acid level (average value) of the group mice.
［参考例１：ヘスペリジンの長期投与試験］
　ヘスペリジンは急性試験において血中尿酸値を改善することが報告されている（Ｒｅｄｏｘ　Ｒｅｐ.，　２０１２年，１７巻（５号），ｐｐ．２１９－２２６）。そこで、ヘスペリジンの長期投与試験による血中尿酸値の改善効果について検証を実施した。 [Reference Example 1: Hesperidin long-term administration test]
Hesperidin has been reported to improve blood uric acid levels in acute tests (Redox Rep., 2012, 17 (5), pp.219-226). Therefore, the effect of improving the blood uric acid level in a long-term administration test of hesperidin was verified.
　マウス（７週齢、Ｃ５７ＢＬ／６Ｊマウス、チャールスリバー社）は、１週間の馴化飼育を経た後、８週齢の時点で試験に供した。馴化飼育期間及びその後の試験期間を通して、マウスは、温度２３±１℃、湿度５５％、１２時間明暗サイクルの環境下で飼育した。馴化期間の飼料はＭＦ飼料(オリエンタル酵母社製)を使用し、飼料及び水道水は自由摂取とした。 Mice (7-week-old, C57BL / 6J mice, Charles River) were subjected to testing at the age of 8 weeks after one week of acclimatization. Throughout the acclimatization period and subsequent test periods, the mice were housed in an environment with a temperature of 23 ± 1 ° C., a humidity of 55%, and a 12-hour light-dark cycle. The feed during the acclimatization period was MF feed (Oriental Yeast Co., Ltd.), and feed and tap water were freely consumed.
　馴化飼育期間経過後、試験開始時に尾静脈より採血を行い、試験開始時の血中尿酸値が群間で差の無いように群分けした。その後、高尿酸血症誘導食として６０％フルクトース（特級、和光純薬工業社製）、３％尿酸（和光純薬工業社製）、２％オキソン酸カリウム（シグマアルドリッチ社製）を含むＭＦ飼料を試験飼料として対照群のマウスに与えた（Ｎ＝９）。また、ヘスペリジン群のマウスには試験飼料に更にヘスペリジンを０．３９％混餌した飼料を与えた（Ｎ＝５）。ヘスペリジン投与試験ではプラスチック製イノケージに２－３匹/ケージで２週間集団飼育した。
　なお、ヘスペリジン換算値を基準とすると、０．３９％のヘスペリジンは、０．５０％のＧＬＰＰに相当するものである。 After the acclimatization period, blood was collected from the tail vein at the start of the test, and the blood uric acid level at the start of the test was divided into groups so that there was no difference between the groups. Thereafter, MF feed containing 60% fructose (special grade, manufactured by Wako Pure Chemical Industries, Ltd.), 3% uric acid (produced by Wako Pure Chemical Industries, Ltd.), and 2% potassium oxonate (produced by Sigma Aldrich) as a hyperuricemia-inducing diet. Was fed to a control group of mice as a test diet (N = 9). Further, mice in the hesperidin group were fed a diet in which 0.39% hesperidin was further added to the test diet (N = 5). In the hesperidin administration test, 2-3 animals / cage were housed in a plastic ino cage for 2 weeks.
In addition, on the basis of the value converted to hesperidin, 0.39% hesperidin corresponds to 0.50% GLPP.
　週に１回体重測定を行い、２週後に経時採血を尾静脈より行った。採血した血液はすぐに氷冷し、１時間経った後に遠心分離して血清を得た（分析時まで－２０℃保存）。試験開始直後から２週後にかけて、実施例１と同様の方法により各群のマウスの血中尿酸値を測定した。 Body weight was measured once a week, and blood was collected from the tail vein after 2 weeks. The collected blood was immediately ice-cooled, and after 1 hour, it was centrifuged to obtain serum (stored at −20 ° C. until analysis). From the start of the test to 2 weeks later, the blood uric acid level of each group of mice was measured in the same manner as in Example 1.
　図３にヘスペリジン群及び対照群の血中尿酸値の測定結果を示す。試験開始後０週及び２週における各群マウスの血中尿酸値測定結果を、図３（ａ）、図３（ｂ）に示す。グラフの値は、各群における血中尿酸値の平均値を表し、エラーバーはその標準誤差を表す。 FIG. 3 shows the measurement results of blood uric acid levels in the hesperidin group and the control group. The blood uric acid level measurement results of the mice in each group at 0 and 2 weeks after the start of the test are shown in FIGS. 3 (a) and 3 (b). The value in the graph represents the average value of blood uric acid in each group, and the error bar represents the standard error.
　図３に示すとおり、ヘスペリジン群において、２週経過時点の血中尿酸値の減少率は１２％であり、ｔ検定において有意差は確認できなかった。 As shown in FIG. 3, in the hesperidin group, the rate of decrease in blood uric acid level after 2 weeks was 12%, and no significant difference could be confirmed by t-test.
　以上のとおり、ヘスペリジンを摂取させることで長期的な血中尿酸値の上昇が抑制されることは確認できなかった。 As described above, it was not possible to confirm that long-term increase in blood uric acid level was suppressed by ingesting hesperidin.

Claims (10)

  1. 　モノグルコシルヘスペリジンを有効成分とする血中尿酸値改善剤。 A blood uric acid level improver containing monoglucosyl hesperidin as an active ingredient.
  2. 　モノグルコシルヘスペリジンを含む酵素処理ヘスペリジンを有効成分とする血中尿酸値改善剤。 A blood uric acid level improver containing enzyme-treated hesperidin containing monoglucosyl hesperidin as an active ingredient.
  3. 　前記酵素処理ヘスペリジンがレモン抽出物の酵素処理物である、請求項２に記載の血中尿酸値改善剤。 The blood uric acid level improving agent according to claim 2, wherein the enzyme-treated hesperidin is an enzyme-treated product of lemon extract.
  4. 　前記レモン抽出物がグリーンレモン抽出物である、請求項３に記載の血中尿酸値改善剤。 The blood uric acid level improving agent according to claim 3, wherein the lemon extract is a green lemon extract.
  5. 　長期投与用である、請求項１～４のいずれか一項に記載の血中尿酸値改善剤。 The blood uric acid level improving agent according to any one of claims 1 to 4, which is for long-term administration.
  6. 　モノグルコシルヘスペリジンを有効成分とする血中尿酸値改善用飲食品。 Food and drink for improving blood uric acid level, which contains monoglucosyl hesperidin as an active ingredient.
  7. 　モノグルコシルヘスペリジンを含む酵素処理ヘスペリジンを有効成分とする血中尿酸値改善用飲食品。 Food / beverage products for improving blood uric acid level containing enzyme-treated hesperidin containing monoglucosyl hesperidin as an active ingredient.
  8. 　前記酵素処理ヘスペリジンがレモン抽出物の酵素処理物である、請求項７に記載の血中尿酸値改善用飲食品。 The food and drink for improving blood uric acid level according to claim 7, wherein the enzyme-treated hesperidin is an enzyme-treated product of lemon extract.
  9. 　前記レモン抽出物がグリーンレモン抽出物である、請求項８に記載の血中尿酸値改善用飲食品。 The food and drink for improving blood uric acid level according to claim 8, wherein the lemon extract is a green lemon extract.
  10. 　長期投与用である、請求項６～９のいずれか一項に記載の血中尿酸値改善用飲食品。 The food / beverage product for improving blood uric acid level according to any one of claims 6 to 9, which is for long-term administration.
PCT/JP2018/003851 2017-02-21 2018-02-05 Blood uric acid level improving agent and food/drink for improving blood uric acid level WO2018155150A1 (en)

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