WO2018101102A1 - Inhibiteur d'élévation de pig postprandial - Google Patents

Inhibiteur d'élévation de pig postprandial Download PDF

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Publication number
WO2018101102A1
WO2018101102A1 PCT/JP2017/041668 JP2017041668W WO2018101102A1 WO 2018101102 A1 WO2018101102 A1 WO 2018101102A1 JP 2017041668 W JP2017041668 W JP 2017041668W WO 2018101102 A1 WO2018101102 A1 WO 2018101102A1
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Prior art keywords
arabinoxylan
agent
gip
composition
food
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PCT/JP2017/041668
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English (en)
Japanese (ja)
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弥生 細田
潤 出口
卓也 森
史明 岡原
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花王株式会社
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • 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
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a postprandial GIP elevation inhibitor.
  • Gastric inhibitory polypeptide also referred to as Glucose-dependent insulinotropic polypeptide; hereinafter simply referred to as “GIP”
  • GIP Glucose-dependent insulinotropic polypeptide
  • It is one of the gastrointestinal hormones belonging to the family. GIP is secreted from K cells present in the small intestine by intake of lipids and carbohydrates, and promotes insulin secretion in pancreatic ⁇ cells. GIP is also known to have gastric acid secretion inhibitory action and gastric movement inhibitory action (see Non-Patent Documents 1 to 3). Therefore, it is considered that the suppression of the increase in GIP is effective in preventing or improving stomach sag.
  • the present invention relates to a postprandial GIP increase inhibitor containing arabinoxylan as an active ingredient. Moreover, this invention relates to the food-drinks composition for postprandial GIP raise suppression containing arabinoxylan as an active ingredient. The present invention also relates to a preventive or ameliorating agent for stomach stagnation comprising arabinoxylan as an active ingredient. Furthermore, this invention relates to the food-drinks composition for the prevention or improvement of stomach stagnation containing arabinoxylan as an active ingredient.
  • FIG. 1 (A) is a graph showing changes over time in the GIP concentration when a test meal was fed to mice.
  • FIG. 1B is a graph showing the area (iAUC) under the GIP concentration-time curve of the graph shown in FIG.
  • the present invention relates to the provision of a postprandial GIP increase inhibitor or a food / beverage composition for suppressing postprandial GIP increase that suppresses GIP increase after meals or after feeding. Further, the present invention makes use of the effect of the postprandial GIP increase inhibitor or the food / beverage composition for suppressing postprandial GIP increase, and as a means for its administration, a preventive or ameliorating agent for stomach stagnation, or for preventing or improving gastric stagnation
  • the present invention relates to the provision of a food or drink composition.
  • the present inventors diligently investigated a substance that can suppress an increase in GIP after eating or after feeding. As a result, the present inventors have found that arabinoxylan has an action of suppressing an increase in GIP after eating or feeding, and is useful for preventing or improving stomach sag.
  • the present invention has been completed based on these findings.
  • “suppression of postprandial GIP elevation” refers to a diet or diet containing lipids and carbohydrates, in particular from K cells present in the small intestine that are produced by ingesting a diet or diet rich in lipids such as fats and fats and fatty acids.
  • the “suppression of postprandial GIP increase” in the present specification preferably means suppression of an increase in GIP concentration resulting from intake of lipids, carbohydrates, or lipids and carbohydrates after meals or after feeding.
  • suppression of the increase in GIP after a meal or after feeding does not necessarily mean that the increase in GIP caused after a meal or after feeding is completely suppressed.
  • Postprandial GIP increase inhibitory action in the present specification means a GIP secretion inhibitory action that suppresses an increase in GIP concentration by suppressing GIP secretion from K cells by stimulation of lipids and carbohydrates derived from meals or diets. To do.
  • the “postprandial GIP increase inhibitory action” in the present specification can be determined based on the action of suppressing the GIP increase caused by any lipid or carbohydrate. For example, ingestion of any lipid or sugar (for example, oleic acid), and administration or ingestion of any lipid or sugar (for example, oleic acid), blood GIP concentration in a test group that has administered or ingested a test substance The control group was compared with the blood GIP concentration.
  • the molecular weight of arabinoxylan used in the present invention can be appropriately set within a range not impairing the effects of the present invention.
  • the mass average molecular weight (Mw) of arabinoxylan is preferably 300 or more, more preferably 10,000 or more, and more preferably 50,000 or more.
  • the upper limit is preferably 1,000,000, more preferably 500,000, and more preferably 200,000.
  • 300 to 500,000 is preferable, and 50,000 to 200,000 is more preferable.
  • the ratio of arabinose and xylose constituting the arabinoxylan used in the present invention can be set as appropriate within a range not impairing the effects of the present invention.
  • the ratio of arabinose to xylose is preferably 0.01: 1 or more, more preferably 0.05: 1 or more, and more preferably 0.1: 1 or more on a mass basis.
  • the upper limit is preferably 10: 1, more preferably 2: 1 and more preferably 1.2: 1.
  • 0.01: 1 to 10: 1 is preferable, 0.05: 1 to 2: 1 is more preferable, and 0.1: 1 to 1.2: 1 is more preferable.
  • the arabinoxylan used in the present invention may be constituted by saccharides other than these monosaccharides in addition to arabinose and xylose.
  • Examples of the feed composition include small animal feed used for rabbits, rats, mice and the like, pet food used for dogs, cats, small birds, squirrels and the like.
  • These food / beverage composition, feed composition, pet food composition, and the like contain the postprandial GIP increase inhibitor of the present invention, the preventive or ameliorating agent of the present invention, or the above-mentioned active ingredients, and include food ingredients such as , Sweeteners, colorants, antioxidants, additives such as vitamins, fragrances, minerals, etc., proteins, lipids, carbohydrates, carbohydrates, dietary fibers and the like can be appropriately combined and prepared according to conventional methods.
  • administering or ingesting simultaneously means administering or ingesting the postprandial GIP elevation inhibitor, preventive or ameliorating agent of the present invention, or a food or drink composition, and a meal or food at the same time,
  • administering or ingesting a meal or diet containing a postprandial GIP elevation inhibitor, or a preventive or ameliorating agent the postprandial GIP elevation inhibitor, preventive or ameliorating agent of the present invention, and a food or beverage composition
  • the food is administered or ingested separately in time, but the postprandial GIP elevation inhibitor, the preventive or ameliorating agent of the present invention, the food or drink composition, and the meal or food are both so as to reach the intestine almost simultaneously.
  • Timing of administering or ingesting a postprandial GIP elevation inhibitor, preventive or ameliorating agent, or food / beverage product composition, and a meal or diet, respectively, of the invention It refers to be appropriately adjusted.
  • the postprandial GIP increase inhibitor, prevention or improvement of the present invention for causing a postprandial GIP increase inhibitor, prevention or improvement agent, or a food or drink composition of the present invention and a meal or food to reach the intestinal tract almost simultaneously.
  • the timing of administration or ingestion of an agent or food / beverage product composition is preferably before or during administration or ingestion of a meal or food, and more preferably between 30 minutes before administration or ingestion of food or food More preferably, the postprandial GIP elevation inhibitor, the preventive or ameliorating agent of the present invention, the food or drink composition, and the meal or diet are simultaneously administered or ingested.
  • carbohydrate components contained in the meal or diet there are no particular limitations on the carbohydrate components contained in the meal or diet, and examples include rice, starch, wheat flour, sugar, fructose, glucose, glycogen and the like.
  • the intake amount of the lipid and carbohydrate is not particularly limited as long as it is within the range included in a normal meal or diet.
  • the sugar mass and lipid amount for secreting GIP vary depending on the individual.
  • a human or a non-human mammal for example, dog, cat, hamster
  • the subject of ingestion or administration includes humans and non-human mammals who have symptoms of stomach upset, humans and non-human mammals who may be at risk, and humans and non-humans who are expected to prevent the disease / symptoms. Mammals are also included.
  • ⁇ 9> The above-mentioned ⁇ 1>, wherein the compounding amount or content of the active ingredient is 5% by mass or more, preferably 9% by mass or more and 50% by mass or less, preferably 30% by mass or less, based on the total amount of the composition.
  • ⁇ 10> A non-therapeutic method for suppressing postprandial GIP elevation, or a non-therapeutic method for preventing or ameliorating stomach stagnation, comprising administering or ingesting arabinoxylan.
  • ⁇ 11> The method according to ⁇ 10>, wherein GIP secretion from K cells present in the small intestine is suppressed, thereby suppressing postprandial GIP elevation, or preventing or improving stomach leaning.
  • ⁇ 12> The above ⁇ 10> or ⁇ 11, which suppresses an increase in post-meal GIP, or prevents or improves stomach stagnation by suppressing an increase in GIP concentration resulting from intake of lipids, carbohydrates, or lipids and carbohydrates The method according to item>.
  • ⁇ 13> The ⁇ 10>, wherein the arabinoxylan is derived from at least one plant selected from the group consisting of wheat, barley, oats, rye, rice, millet, millet, corn, and bamboo, preferably wheat.
  • ⁇ 14> The mass average molecular weight of the arabinoxylan is 300 or more, preferably 10,000 or more, more preferably 50,000 or more, and 1,000,000 or less, preferably 500,000 or less, more preferably 200,000 or less.
  • ⁇ 21> Use of arabinoxylan as a postprandial GIP elevation inhibitor, or as an agent for preventing or improving stomach sag.
  • ⁇ 22> Use of arabinoxylan for the production of a postprandial GIP elevation inhibitor, or the prevention or amelioration agent of stomach sag.
  • ⁇ 23> A method of using arabinoxylan as a postprandial GIP elevation inhibitor, or as a preventive or ameliorating agent for stomach upset.
  • ⁇ 24> A method for suppressing postprandial GIP elevation, or a method for preventing or improving stomach sag, using arabinoxylan.
  • ⁇ 25> Any one of the above ⁇ 21> to ⁇ 24>, wherein GIP secretion from K cells existing in the small intestine is suppressed, thereby suppressing postprandial GIP elevation, or preventing or improving stomach sag. Use or method.
  • ⁇ 26> The above ⁇ 21> to ⁇ 25, wherein the increase in GIP concentration caused by intake of lipids, carbohydrates, or lipids and carbohydrates is suppressed, thereby suppressing postprandial GIP increase, or preventing or improving stomach sag > Use or method of any one of>.
  • ⁇ 27> The ⁇ 21>, wherein the arabinoxylan is derived from at least one plant selected from the group consisting of wheat, barley, oats, rye, rice, millet, millet, corn, and bamboo, preferably wheat.
  • ⁇ 28> The mass average molecular weight of the arabinoxylan is 300 or more, preferably 10,000 or more, more preferably 50,000 or more, and 1,000,000 or less, preferably 500,000 or less, more preferably 200,000 or less.
  • ⁇ 31> The use or method according to any one of the above ⁇ 21> to ⁇ 30>, wherein the arabinoxylan is applied under conditions where secretion of GIP after feeding or feeding is enhanced.
  • ⁇ 32> The use or method according to any one of ⁇ 21> and ⁇ 23> to ⁇ 31>, wherein the arabinoxylan is administered or ingested.
  • ⁇ 33> The use or method according to any one of ⁇ 21> to ⁇ 32>, wherein the arabinoxylan is divided into once to several times a day, or can be taken or administered at an arbitrary period and interval.
  • the arabinoxylan intake per meal is 2 g or more, preferably 3 g or more, more preferably 4 g or more, 20 g or less, preferably 10 g or less, more preferably 8 g or less, ⁇ 21> Use or method according to any one of to ⁇ 33>.
  • ⁇ 38> Any one of the above ⁇ 21> to ⁇ 37>, wherein the arabinoxylan is administered or ingested simultaneously with a meal or diet containing an amount of carbohydrate or lipid capable of secreting GIP from K cells present in the small intestine Use or method according to paragraph.
  • ⁇ 39> The use or method according to any one of ⁇ 21> to ⁇ 38>, wherein the arabinoxylan is used non-therapeutically.
  • the mass average molecular weight of the arabinoxylan is 300 or more, preferably 10,000 or more, more preferably 50,000 or more, and 1,000,000 or less, preferably 500,000 or less, more preferably 200,000 or less.
  • the Ara: Xyl ratio of the arabinoxylan is 0.01: 1 or more, preferably 0.05: 1 or more, more preferably 0.1: 1 or more, and 10: 1 or less, preferably 2: 1 or less, based on mass.
  • ⁇ 46> The arabinoxylan or the use according to any one of ⁇ 40> to ⁇ 45>, wherein the arabinoxylan is applied in the form of a pharmaceutical composition.
  • ⁇ 47> The arabinoxylan or the use according to any one of ⁇ 40> to ⁇ 45>, wherein the arabinoxylan is applied in the form of food or beverage.
  • ⁇ 48> The arabinoxylan or the use according to ⁇ 47>, wherein the food or beverage is in the form of a beauty food, a food for a sick person, a nutritional functional food, a food for specified health use or a functional indication food.
  • ⁇ 49> The above arabinoxylan, a human or a non-human mammal with a stomach symptom, or a human or a non-human mammal that may have the symptom, or a human who expects prevention of the disease or symptom
  • ⁇ 50> The arabinoxylan or the use according to any one of ⁇ 40> to ⁇ 49>, wherein the arabinoxylan is applied under conditions where secretion of GIP is enhanced after meal or after feeding.
  • the blending amount or content of the arabinoxylan with respect to the total amount of the composition is 5% by mass or more, preferably 9% by mass or more and 100% by mass or less, preferably 50% by mass or less.
  • ⁇ 55> Any one of the above ⁇ 40> to ⁇ 54>, wherein the arabinoxylan is administered or ingested simultaneously with a meal or diet containing an amount of carbohydrate or lipid capable of secreting GIP from K cells present in the small intestine Item arabinoxylan or use.
  • the obtained wheat bran extraction residue was extracted with a 0.4 M aqueous sodium hydroxide solution (600 mL) at 80 ° C. for 1.5 hours.
  • the extract was separated, and the residue was extracted with a 0.3 M aqueous sodium hydroxide solution (600 mL) at 80 ° C. for 1.5 hours.
  • the residue was extracted again under the same conditions.
  • 2M hydrochloric acid the extract obtained by extraction with a 0.4M aqueous sodium hydroxide solution and a 0.3M aqueous sodium hydroxide solution was neutralized. Na 2 HPO 4 ⁇ 12H 2 O and NaH 2 PO 4 (anhydrous) were added to the neutralized extract to prepare a 0.08M phosphate buffer solution (pH 6.0).
  • the obtained suspension was centrifuged, and the supernatant was collected. 99.5% ethanol was added to the collected supernatant to prepare a 65% (v / v%) ethanol aqueous solution of the enzyme treatment reaction solution. After mixing well, the mixture was allowed to stand at room temperature for 1 hour, and centrifuged to obtain a precipitate. A 70% aqueous ethanol solution was added to the precipitate and stirred well, followed by centrifugation. Then, the supernatant was removed, 99.5% ethanol was added and stirred, centrifuged, and the supernatant was removed. Acetone was further added, the precipitate was stirred, centrifuged to remove the supernatant, and the precipitate was dried with a vacuum pump to obtain 12.1 g of an arabinoxylan preparation.
  • the molecular weight of the arabinoxylan preparation was analyzed using a device made by Shodex. When calculating the molecular weight, the pullulan retention time of each molecular weight was used as a reference. (Molecular weight distribution measurement conditions) Column: Shodex GPC KD-802M-803M Mobile phase: 2.5% LiCl / DMI Flow rate: 0.5 mL / min Column temperature: 60 ° C Detector: RI Standard products: Pullulan Mw 5,900, 11,800, 47,100, 107,000, 708,000 (5 points)
  • the component composition of the arabinoxylan preparation determined by the above method is as shown in Table 2 below.
  • Preparation Example 2 Preparation of Test Food
  • 10 test food
  • % AX supplemented food and“ 20% AX supplemented food ”.
  • Table 4 shows the composition of the 10% AX-added food and 20% AX-added food together with the composition of the control food and the low-fat powdered feed used in the following test examples.
  • the calorie of the arabinoxylan preparation was calculated as 0 kcal / g.
  • control food 212 mg the 10% AX-added food 233 mg, and the 20% AX-added food 254 mg were fed to the mouse so that the calorie intake of each test food was equal.
  • mice were fasted for 20 hours, and initial blood was collected from the orbital venous plexus under isoflurane inhalation anesthesia. Thereafter, 913 calories of each test meal were freely taken for 30 minutes, and blood was collected from the orbital venous plexus under isoflurane inhalation anesthesia 30 minutes, 60 minutes, and 120 minutes after the start of the intake of the test meal.
  • a heparinized hematocrit micro blood collection tube manufactured by VITREX was used for blood collection.
  • the collected blood was stored in ice and then centrifuged at 11,000 rpm for 6 minutes to obtain plasma. The obtained plasma was stored at ⁇ 80 ° C. until the GIP concentration was measured.
  • the plasma GIP concentration was quantified by ELISA (Rat / Mouse GIP (total) ELISA Kit, Linco Research / Millipore co.), And a graph showing changes in GIP concentration over time was prepared. The result is shown in FIG. Furthermore, the area under the curve (incremental AUC) of the graph shown in FIG. 1 (A) was calculated. The result is shown in FIG. Numerical values are shown as mean ⁇ standard deviation. About the statistically significant difference between the groups of FIG. 1 (A), the GIP value in each time point was tested using the One Way ANOVA, post-hoc, Bonferroni method with respect to the control food. Statistical significance between the groups in FIG. 1B was tested using the One Way ANOVA, post-hoc, Bonferroni method against the control diet. Two-sided test determined that there was a significant difference when the p-value was 0.05 or less. When the p value is 0.05 or less, “*” is attached, and when the p value is 0.01 or less, “**” is attached to FIG.
  • arabinoxylan that suppresses an increase in GIP concentration after meal or after feeding is a GIP increase inhibitor, a stomach sag preventive or ameliorating agent, a food or drink composition for suppressing GIP increase, and a food or drink composition for preventing or improving stomach sag It can be an active ingredient of a product.

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Abstract

L'invention concerne : un inhibiteur d'élévation de polypeptide inhibiteur gastrique qui contient de l'arabinoxylane en tant que principe actif ; et un agent pour prévenir ou améliorer la sensation de lourdeur dans l'estomac.
PCT/JP2017/041668 2016-12-02 2017-11-20 Inhibiteur d'élévation de pig postprandial WO2018101102A1 (fr)

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JP2007182395A (ja) * 2006-01-05 2007-07-19 Nisshin Pharma Inc 脂肪低下組成物

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EP1643861B1 (fr) * 2003-07-15 2011-05-11 Nestec S.A. Composition fluide de nutrition riche en fibres alimentaires et en calories pour la sante de l'intestin des patients âgés
JP5457064B2 (ja) * 2009-04-03 2014-04-02 花王株式会社 血中ｇｉｐ及び／又は血中インスリン上昇抑制剤
JP2012171914A (ja) * 2011-02-22 2012-09-10 Kao Corp Ｇｉｐ上昇抑制剤
JP6026723B2 (ja) * 2011-02-22 2016-11-16 花王株式会社 Ｇｉｐ上昇抑制剤

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JP2007182395A (ja) * 2006-01-05 2007-07-19 Nisshin Pharma Inc 脂肪低下組成物

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Title
CHRISTENSEN K. L. ET AL.: "Concentrated arabinoxylan but not concentrated beta-glucan in wheat bread has similar effects on postprandial insulin as whole grain rye in Porto-arterial catheterized pigs.", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 61, no. 32, August 2013 (2013-08-01), pages 7760 - 7768, XP055513791 *
HARTVIGSEN ML ET AL.: "Effects of concentrated arabinoxylan and beta-glucan compared with refined wheat and whole grain rye on glucose and appetite in subjects with the metabolic syndrome: a randomized study.", EUR. J. CLIN. NUTR., vol. 68, 2014, pages 84 - 90 *
LU Z. X. ET AL.: "Arabinoxylan fiber, a byproduct of wheat flour processing, reduces the postprandial glucose response in normoglycemic subjects.", THE AMERICAN JOURNAL OF CLINICAL NUTRITION, vol. 71, no. 5, May 2000 (2000-05-01), pages 1123 - 1128, XP002482172 *
MIYAGAWA, JUNICHIRO ET AL.: "Gastrointestinal-Derived Hormones: GIP, GLP-1 and Insulin Resistance", ADIPOSCIENCE, vol. 4, no. 1, 2007, pages 17 - 24 *
MORGAN L. M. ET AL.: "The effect of non-starch polysaccharide supplementation on circulating bile acids, hormone and metabolite levels following a fat meal in human subjects.", BRITISH JOURNAL OF NUTRITION, vol. 70, no. 02, September 1993 (1993-09-01), pages 491 - 501, XP055513794 *

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