WO2006064761A1 - Agent régulateur d'adiponectine et aliments, boissons, additifs alimentaires et médicaments incluant ledit agent - Google Patents

Agent régulateur d'adiponectine et aliments, boissons, additifs alimentaires et médicaments incluant ledit agent Download PDF

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Publication number
WO2006064761A1
WO2006064761A1 PCT/JP2005/022769 JP2005022769W WO2006064761A1 WO 2006064761 A1 WO2006064761 A1 WO 2006064761A1 JP 2005022769 W JP2005022769 W JP 2005022769W WO 2006064761 A1 WO2006064761 A1 WO 2006064761A1
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Prior art keywords
adiponectin
hop
extract
polyphenol
apple
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PCT/JP2005/022769
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English (en)
Japanese (ja)
Inventor
Yoko Akazome
Tomomasa Kanda
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Asahi Breweries, Ltd.
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Publication of WO2006064761A1 publication Critical patent/WO2006064761A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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
    • 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)
    • 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)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • Adiponectin regulator for food and drink containing the same, food additive and pharmaceutical
  • the present invention relates to an adiponectin regulator obtained from a hop koji extract or an apple extract, a food or drink containing the same, a food additive, and a medicine.
  • Non-patent Document 1 Non-patent Document 1
  • Adiponectin was discovered as a secreted protein that is highly expressed specifically in adipocytes. In later studies, adhesion of monocytes to vascular endothelial cells and the proliferation of smooth muscle cells were suppressed. It became clear that it has an anti-arteriosclerotic action.
  • Non-patent Document 2 Regarding the relationship with diabetes mellitus, in animal models, in type II diabetic monkeys, adiponectin decreased with increasing insulin resistance, and correlated with the glucose uptake index (M value) in the glucose clamp. It has been shown that blood adiponectin increases (Non-patent Document 2). In addition, administration of physiological concentrations of adiponectin to type II diabetic mice (db / db mice, KKA y mice) improves insulin resistance, and adiponectin administration also improves insulin resistance in fat-deficient mice. It has been shown that reduced or deficient adiponectin expression is responsible for obesity insulin resistance, and thus obesity and type 2 diabetes. (Non-Patent Document 3).
  • adiponectin a protein specific to adipose tissue
  • vascular smooth muscle proliferation migration inhibition
  • anti-arteriosclerosis monocyte and macrophage activity
  • anti-inflammatory e.g., IL-12
  • recent studies have also confirmed that it has the effects of suppressing liver fibrosis and promoting normal hepatocyte proliferation.
  • Non-patent document 1 Guidelines for the treatment of arteriosclerotic diseases, Japan Atherosclerosis Society, 2002
  • Non-patent document 2 DIABETES Vol.50: 1126 ⁇ 1133 (2001)
  • Non-Patent Document 3 Nature Medecine Vol. 7: 941-946 (2001)
  • the problem to be solved by the present invention is to provide an adiponectin modulator, food / beverage product, food additive or medicine that has an effect of regulating adiponectin and has an adiponectin regulatory action that is derived from natural substances and has high safety There is to do.
  • the gist of the present invention is as follows.
  • An adiponectin regulator characterized by comprising a hop koji extract or an apple extract as an active ingredient.
  • the hop koji extract is a hop koji-derived polyphenol (1)
  • An adiponectin regulator characterized by containing, as an active ingredient, a substance that is a hop koji extract and does not permeate the membrane when treated with an ultrafiltration membrane having a molecular weight cut off of 1,000 or more.
  • An adiponectin regulator that is a polyphenol-like substance contained in hop koji and does not permeate the membrane when treated with an ultrafiltration membrane having a molecular weight cut off of 1,000 or more.
  • the adiponectin modulator comprising the hop koji extract or apple extract of the present invention as an active ingredient can regulate adiponectin with very few side effects.
  • the adiponectin modulating agent in the present invention refers to those that normally adjust the blood concentration of adiponectin.
  • the hop koji-derived polyphenol in the present invention contains the derived polyphenol as an active ingredient in the hop koji extract.
  • the adiponectin regulator in the present invention may be either a hop koji extract or a hop koji-derived polyphenol, but is preferably a hop koji-derived polyphenol.
  • the hop koji extract containing the hop koji-derived polyphenol used in the present invention is obtained by removing the rubulin portion from the hop koji. Generally, the hop koji is crushed and then sieved. Hops are obtained by removing the Lublin part. However, in recent beer brewing, in order to save the trouble of sieving and removing hop cake, the hop fruit is directly formed into pellets without removing hop cake that is not useful for beer brewing. As such, it tends to be used for beer brewing. Accordingly, the raw material of the present invention is not particularly limited as long as it contains hop cake, and there is no problem even if hop fruit or hop pellet containing hop cake is used as a raw material.
  • the extraction method of the hop koji extract is not particularly limited, but, for example, hop koji or hop pellets containing hop koji or hop koji as a raw material is preferably 4 to 95 ° C, preferably Extract at 30-60 ° C with 0-50%, preferably 10-40% ethanol.
  • the ratio of the raw material to the extraction solvent is 1:20 to 100 (weight ratio), preferably 1:30 to 90 (weight ratio), and is carried out with stirring for 20 to 60 minutes, preferably 30 to 50 minutes. Further clarification is performed by filtration through diatomaceous earth (trade name “Silica 300S”, manufactured by Chuo Silica Co., Ltd.) at 5 to 75 ° C., preferably 15 to 25 ° C. Since hop koji extract has a neutral fat metabolism control action, it is useful as a neutral fat reduction metabolism control agent.
  • the hop koji extract or hop koji-derived polyphenol has an adiponectin-modulating action and is therefore useful as an adiponectin-modulating agent.
  • hop cocoon extract power To obtain hop cocoon-derived polyphenol, for example, hop cocoon extract is adsorbed with an adsorption resin that adsorbs a polyphenol-like substance, and hop cocoon-derived polyphenol-like is extracted from the hop cocoon extract.
  • the material may be separated and purified.
  • the adsorption treatment method is not particularly limited.
  • the hop koji extract may be adsorbed on the adsorption resin at 0 to 40 ° C, preferably 15 to 25 ° C.
  • the adsorbed resin is not particularly limited as long as it adsorbs a polyphenol-like substance.
  • hydrophilic bur polymer resin (“Toyopearl HW40” manufactured by Toso Co., Ltd.), styrene-di-vinylbenzene resin (Mitsubishi) "Separbeads SP-825" manufactured by Eigakusha), gel-type synthetic resin (Mitsubishi “Diaion HP-20” manufactured by Kagaku Co., Ltd.).
  • the hop koji extract is passed through an adsorption column packed with these adsorbents to adsorb polyphenol-like substances.
  • pure water is passed through to remove non-adsorbed substances (saccharides, organic acids, etc.) in the column, and then the polyphenol-like substance is eluted with 10 to 90%, preferably 30 to 80% ethanol. Good.
  • hop koji extract or the hop koji-derived polyphenol-like substance a substance that does not permeate the membrane when treated with an ultrafiltration membrane having a fractional molecular weight of 1,000 or more is preferable in terms of regulating adiponectin.
  • the treatment liquid containing the hop koji extract or the hop koji-derived polyphenol-like substance obtained in the above extraction step or adsorption step has a molecular weight cutoff of 1,000 or more, preferably 10,000 to 50,000. Treat with filtration membrane. At that time, if necessary, the treatment liquid containing the hop koji-derived polyphenol-like substance can be concentrated under reduced pressure to lower the ethanol concentration. Depending on the concentration of the organic solvent in the extraction solvent and the ratio of the extraction solvent and hops or hops, the treatment is carried out until the amount of the remaining liquid is approximately iZio to iZioo, preferably 1Z20 to 1Z100 at the start of the treatment. .
  • the pressure at that time is 9.8 kPa to 981 kPa, preferably 98 kPa to 686 kPa. It can be used in the liquid state as it is, but it can also be dried as described below.
  • the obtained fractional force is also concentrated under reduced pressure at 25 to 100 ° C, preferably 35 to 90 ° C, and spray-dried or lyophilized with the concentrated solution as it is or with the addition of a powder auxiliary such as dextrin. Get the extracted powder product.
  • the method for obtaining a hop koji-derived polyphenol-like substance that does not pass through the membrane when treated with an ultrafiltration membrane having a molecular weight cut off of 1,000 or more is limited to the above method.
  • the treatment liquid that does not permeate the ultrafiltration membrane may be adsorbed with a gel polymer.
  • the apple-derived polyphenol in the present invention contains the derived polyphenol as an active ingredient in the apple extract.
  • the adiponectin regulator in the present invention may be either an apple extract or an apple-derived polyphenol, but is preferably a lingo-derived polyphenol. Highly purified apple-derived polyphenols are used for food and drink When it is added to the product, it is difficult to generate odors and turbidity, and the influence of the flavor on the food and drink itself can be suppressed, so that the applicability on the cake is high.
  • An apple extract containing an apple-derived polyphenol used in the present invention is a fruit of a genus Rosaceae, for example, cultivars such as Fuji, Mutsu, Tsugaru, Starking Delicious, and original apples. Obtained by extraction by known extraction means.
  • the fruit both a mature fruit and an immature fruit can be used. However, since the fruit contains more polyphenol compounds and contains a large amount of various active ingredients having a wide range of physiological effects, Particularly preferred.
  • the apple-derived polyphenol contained in the apple extract of the present invention has a polyphenol fraction purified from an apple fruit, a juiced fruit juice of an immature fruit, or an extract, Purification of the polyphenol fraction is carried out by treating the juice and extract with an adsorbent, and the fraction adsorbed on the adsorbent (hereinafter referred to as the adsorbed fraction) contains polyphenol.
  • the adsorbent is not particularly limited as long as it adsorbs polyphenol!
  • / ⁇ is, for example, a hydrophilic bur polymer resin (“Toyopearl HW40J” manufactured by Toso Co., Ltd.), styrene-dibul benzene resin ( Examples include “Separbeads SP-850” manufactured by Mitsubishi Chemical Corporation, and gel-type synthetic resins (“Diaion HP-20” manufactured by Mitsubishi Chemical Corporation).
  • the polyphenol fraction is purified by eluting the adsorbed fraction adsorbed on the adsorbent with an alcohol solvent such as hydrous ethanol.
  • the polyphenol fraction can then be concentrated to obtain a liquid formulation, and further, a powder formulation can be obtained by subjecting the liquid formulation to spray drying or freeze drying.
  • the washed raw material was obtained by crushing at pH 3.2 to 4.6, preferably pH 3.5 to 4.3.
  • Further clarification is performed by filtration to obtain clarified juice.
  • partitioning and filtering with an organic solvent such as hexane or black mouth form can be performed to obtain an apple extract as a clarified extract.
  • the clarified extract is then added to 0-40. . C, L ⁇ «15-25. C, pHl. 5 to 4.2, preferably pH 3.0 to 4.0, passed through an adsorption column (trade name “Separbeads SP-850”, manufactured by Mitsubishi Chemical Corporation) filled with the above adsorbent, and polyphenol To adsorb. Subsequently, pure water is passed through to remove non-adsorbed substances (saccharides, organic acids, etc.) in the column, and then the adsorbed fraction is eluted with 10 to 90%, preferably 30 to 80% ethanol.
  • the obtained adsorption fraction can also be concentrated by distilling ethanol under reduced pressure at 25 to 100 ° C, preferably 35 to 90 ° C, and leaving the concentrated solution as it is as a liquid apple-derived polyphenol.
  • powder auxiliary agents such as dextrin may be added and spray-dried or freeze-dried to obtain an apple-derived polyphenol extracted powder product.
  • the daily dose for adults to obtain the effect of regulating adiponectin by the adiponectin modulating agent of the present invention is 100 to 2500 mg as hop koji extract or hop koji polyphenol.
  • it is 150-1500 mg, More preferably, it is 150-1000 mg, It is especially preferable that it is 150-750 mg.
  • the adiponectin modulating agent of the present invention when used, in view of absorption of polyphenols, it is more preferable to take the amount of hop koji extract or hop koji-derived polyphenol per day in a smaller number of times. It is easy to express the action of polyphenols.
  • the adult daily dose for obtaining the effect of regulating adiponectin by the adiponectin modulator of the present invention is 10 0 as apple extract or apple polyphenol.
  • ⁇ 2500 mg preferably 150-1500 mg, more preferably 150-1000 mg, especially 150-750 mg.
  • the adiponectin modulating agent of the present invention when used, in view of the absorption of polyphenols, it is more effective to take the amount of apple extract per day or the amount of apple-derived polyphenol in a smaller number of times.
  • the blood concentration is high and the action of polyphenols is likely to occur.
  • the adiponectin regulator of the present invention can be used by adding as a food additive to foods in general, including beverages, such as soups, beverages (juice, mineral water, coffee, tea, non-alcoholic beer, etc. ), Confectionery (gum, candy, chocolate, Suitable for snacks, jellies, etc.), potatoes (soba, udon, ramen, etc.), alcoholic beverages (beer, sparkling liquor, cocktail, chuhai, shochu, sake, whiskey, brandy, wine, etc.).
  • beverages such as soups, beverages (juice, mineral water, coffee, tea, non-alcoholic beer, etc. ), Confectionery (gum, candy, chocolate, Suitable for snacks, jellies, etc.), potatoes (soba, udon, ramen, etc.), alcoholic beverages (beer, sparkling liquor, cocktail, chuhai, shochu, sake, whiskey, brandy, wine, etc.).
  • the pharmaceutical dosage form containing the adiponectin modulating agent of the present invention is not particularly limited, but for example, solid preparations such as tablets, powders, fine granules, granules, capsules, pills, liquids, suspensions Orally administered agents such as syrups and emulsions.
  • This orally administered agent includes excipients, disintegrants, binders, lubricants, surfactants, alcohols, water, water-soluble polymers, sweeteners, corrigents that are commonly used in the art depending on the form. Further, it can be produced by a commonly used method by adding a sour agent, a pharmaceutical carrier and the like.
  • hop blossoms 20 g were pulverized in a mortar and extracted with 2 L of water at 95 ° C. for 40 minutes while stirring. After filtration, the mixture was allowed to cool, and the extract was treated with an ultrafiltration membrane having a molecular weight cut off of 50,000 (XM50 manufactured by Amicon Co., Ltd.) at 98 kPa at room temperature to 20 mL. The obtained remaining liquid was dried under reduced pressure to obtain 0.2 g of a pale yellow powder having an odorless faint bitterness. The yield from hop camellia was 1%.
  • hop koji 20 g was extracted with 600 mL of a 50% aqueous ethanol solution at 80 ° C. for 40 minutes while stirring. After filtration, the extract was treated with an ultrafiltration membrane having a molecular weight cut-off of 10,000 (YM10 manufactured by Amicon Co., Ltd.) at 294 kPa at room temperature to 60 mL. The obtained remaining liquid was freeze-dried to obtain 0.8 g of a pale yellow powder having a faint bitter taste with no odor. The yield from hop cake was 4%.
  • This test meal was formulated with the hop-polyphenol-containing tablet (150 mg / 1 tablet) produced in Example 1 and the polyphenol produced in Comparative Example 1, and the control meal (Bracebo tablet) It was. Before conducting the study, the investigator confirmed that there was no distinction between the test beverage and the placebo tablet due to packages such as flavor and aroma.
  • the study was a parallel two-group comparative study employing a double-blind method with random assignment.
  • the test period was set to a total of 20 weeks, including a pre-observation period of 4 weeks, an intake period of 12 weeks, and an observation period of 4 weeks after the end of intake.
  • the subjects were divided into two groups and ingested the test tablets as follows.
  • Group A Take 4 tablets each of test tablets (150 mg / 1 tablet) containing hops polyphenols before dinner (total 4 tablets / day), hops-polyphenol test tablet intake group
  • Group B Placebo tablets (150 mg / 1 tablet) each 4 tablets before dinner (4 tablets / day in total), the following placebo tablet intake group The subjects except for taking test tablets daily Instructed them not to change their daily life such as eating, smoking and exercising.
  • This test meal was prepared by mixing the tablet containing apple polyphenol produced in Example 2 (150 mg / l tablet) and the polyphenol produced in Comparative Example 2 into a control meal (placebo tablet). .
  • the investigator confirmed that there was no distinction between the test beverage and the placebo tablet due to the sensory features such as flavor and aroma.
  • the study was a parallel two-group comparative study using a double-blind method with random assignment.
  • the test period was set to a total of 20 weeks: a pre-observation period of 4 weeks, an intake period of 12 weeks, and an observation period of 4 weeks after the end of intake.
  • the subjects were divided into two groups and ingested the test tablets as follows.
  • Group A Apple polyphenol-containing test tablets (150 mg / 1 tablet) 4 tablets each before dinner (total 4 tablets / day), hereinafter Apple Polyphenol test tablets intake group
  • Group B Placebo tablets (150 mg / 1 tablet) each 4 tablets before dinner (4 tablets / day in total), the following placebo tablet intake group The subjects except for taking test tablets daily Instructed them not to change their daily life such as eating, smoking and exercising.
  • the adiponectin regulator comprising hop koji extract or apple extract as an active ingredient, and because adiponectin can be regulated with very little side effect, the present invention is useful.
  • the present invention is useful because foods and drinks, food additives and medicines containing the above-mentioned adiponectin regulator as an active ingredient can regulate adiponectin with very few side effects.

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  • Natural Medicines & Medicinal Plants (AREA)
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  • Diabetes (AREA)
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Abstract

La présente invention a pour objet une préparation à base d'adiponectine susceptible de réguler le taux d'adiponectine, issue d'une substance naturelle et, ainsi, très sûre d'emploi. La présente invention décrit plus particulièrement un agent régulateur d'adiponectine caractérisé en ce qu'il contient un extrait de bractée de houblon ou un extrait de pomme.
PCT/JP2005/022769 2004-12-17 2005-12-12 Agent régulateur d'adiponectine et aliments, boissons, additifs alimentaires et médicaments incluant ledit agent WO2006064761A1 (fr)

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JP2004-365799 2004-12-17
JP2004365799 2004-12-17
JP2004-365800 2004-12-17
JP2004365800 2004-12-17

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010109628A1 (fr) * 2009-03-26 2010-09-30 味の素ゼネラルフーヅ株式会社 Composition pharmaceutique pour augmenter la production d'adiponectine et aliment utile pour cela
US9101648B2 (en) 2009-03-26 2015-08-11 Intercontinental Great Brands Llc Pharmaceutical composition comprising mannooligosaccharides derived from coffee for treatment of lifestyle-related disease, and food useful for treatment of lifestyle-related disease
JP6154056B1 (ja) * 2016-03-31 2017-06-28 グレーシャス株式会社 リンゴポリフェノール及びオレアノール酸を含有する食品組成物

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JPH10330278A (ja) * 1997-05-27 1998-12-15 Nikka Uisukii Kk 果実ポリフェノールを有効成分とする生体内脂質代謝制御剤
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JP2003034636A (ja) * 2001-07-19 2003-02-07 Kao Corp 脂質代謝改善剤
JP2004315379A (ja) * 2003-04-11 2004-11-11 Suntory Ltd 発酵茶抽出物を主成分とするアディポネクチン上昇作用を有する組成物

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JP5702713B2 (ja) * 2009-03-26 2015-04-15 味の素ゼネラルフーヅ株式会社 アディポネクチン産生を促進するための医薬組成物およびそれに役立つ食品
US9101648B2 (en) 2009-03-26 2015-08-11 Intercontinental Great Brands Llc Pharmaceutical composition comprising mannooligosaccharides derived from coffee for treatment of lifestyle-related disease, and food useful for treatment of lifestyle-related disease
JP6154056B1 (ja) * 2016-03-31 2017-06-28 グレーシャス株式会社 リンゴポリフェノール及びオレアノール酸を含有する食品組成物

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