WO2010082661A1 - Composition contenant 1,5-ag - Google Patents

Composition contenant 1,5-ag Download PDF

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WO2010082661A1
WO2010082661A1 PCT/JP2010/050551 JP2010050551W WO2010082661A1 WO 2010082661 A1 WO2010082661 A1 WO 2010082661A1 JP 2010050551 W JP2010050551 W JP 2010050551W WO 2010082661 A1 WO2010082661 A1 WO 2010082661A1
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anhydroglucitol
derivatives
group
anhydrofructose
postprandial
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PCT/JP2010/050551
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English (en)
Japanese (ja)
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敦 加藤
圭 竹下
文博 石川
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国立大学法人富山大学
株式会社伏見製薬所
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Priority to JP2010546673A priority Critical patent/JP5637865B2/ja
Publication of WO2010082661A1 publication Critical patent/WO2010082661A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • 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
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30—Artificial sweetening agents
    • A23L27/33—Artificial sweetening agents containing sugars or 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
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30—Artificial sweetening agents
    • A23L27/33—Artificial sweetening agents containing sugars or derivatives
    • A23L27/34—Sugar alcohols
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a composition containing 1,5-D-anhydroglucitol (sometimes abbreviated as “1,5-AG” in this specification). More specifically, a composition for improving postprandial hyperglycemia containing 1,5-AG, use of 1,5-AG for the production of a preventive agent and an improver for postprandial hyperglycemia, and prevention and improvement of postprandial hyperglycemia 1,5-AG for use, method for preventing and improving postprandial hyperglycemia including the step of ingesting the composition, food for preventing and improving postprandial hyperglycemia containing 1,5-AG, 1,5-AG
  • the postprandial blood glucose rise inhibitor which consists of.
  • a composition for improving postprandial hyperlipidemia containing 1,5-AG use of 1,5-AG for the production of a preventive and ameliorating agent for postprandial hyperlipidemia, 1,5-AG for use in prevention and improvement, method for preventing and improving postprandial hyperlipidemia including the step of ingesting the composition, prevention and improvement of postprandial hyperlipidemia containing 1,5-AG
  • the invention relates to a postprandial blood neutral fat elevation inhibitor comprising 1,5-AG, and a fat absorption inhibitor comprising 1,5-AG.
  • adiponectin which is a kind of good adipokine having an insulin sensitivity enhancing action, has attracted attention.
  • Adiponectin enhances insulin sensitivity by activating AMP kinase in muscles and liver, capturing sugar and fat in muscle and burning it, and suppressing gluconeogenesis and fat synthesis in liver while promoting fat burning Has the effect of In patients with low insulin sensitivity, for example, diabetic patients, the blood concentration of adiponectin is low, but it is known that the blood glucose level decreases as the blood concentration of adiponectin increases.
  • adiponectin is not secreted by preadipocytes and hypertrophic adipocytes, but only by small adipocytes (normal fat cells), so it is necessary to increase small adipocytes in order to increase adiponectin .
  • the small adipocytes are obtained by differentiation from preadipocytes or reduction of hypertrophic adipocytes.
  • WO 2005/094866 discloses 10 days for differentiation from preadipocytes into small adipocytes. It is known that these cellular processes require at least 5 days or more. Therefore, it takes at least a weekly time to obtain the effect of increasing the adiponectin in the blood and lowering the blood glucose level by the adiponectin production enhancer.
  • adiponectin is secreted from adipocytes, but has a characteristic that the blood concentration decreases conversely as BMI (body mass index) and visceral fat mass increase.
  • BMI body mass index
  • visceral fat mass increase a characteristic that the blood concentration decreases conversely as BMI (body mass index) and visceral fat mass increase.
  • BMI body mass index
  • visceral fat mass increase a characteristic that the blood concentration decreases conversely as BMI (body mass index) and visceral fat mass increase.
  • An object of the present invention is to provide a composition for improving postprandial hyperglycemia and a composition for improving postprandial hyperlipidemia, which have an effect of quickly suppressing an increase in blood sugar level and blood neutral fat level due to meals. . Also provided are foods for preventing and improving postprandial hyperglycemia, foods for preventing and improving postprandial hyperlipidemia, postprandial blood glucose elevation inhibitors, postprandial blood neutral fat elevation inhibitors, and fat absorption inhibitors having the above-described effects. There is.
  • 1,5-AG for the production of postprandial hyperglycemia preventive and ameliorating agent
  • the use of 1,5-AG for the production of postprandial hyperlipidemia preventive and ameliorating agent postprandial 1,5-AG for use in the prevention and improvement of hyperglycemia
  • 1,5-AG for use in the prevention and improvement of postprandial hyperlipidemia 1,5-AG for use in the prevention and improvement of postprandial hyperlipidemia
  • postprandial hyperglycemia prevention and improvement method postprandial hyperlipidemia It is to provide a method for preventing and ameliorating symptom.
  • a composition for improving postprandial hyperglycemia comprising at least one selected from the group consisting of 1,5-D-anhydroglucitol, 1,5-D-anhydrofructose and derivatives thereof , [2] Selected from the group consisting of 1,5-D-anhydroglucitol, 1,5-D-anhydrofructose and derivatives thereof for the production of a preventive and / or ameliorating agent for postprandial hyperglycemia At least one use, [3] At least selected from the group consisting of 1,5-D-anhydroglucitol, 1,5-D-anhydrofructose and derivatives thereof for use in preventing and / or improving postprandial hyperglycemia One compound, [4] A method for preventing and / or improving postprandial hyperglycemia, comprising a step of ingesting the composition of [1] before, after or at the same time as the food, [5] Prevention and / or improvement of postprandial hyper
  • [12] containing at least one selected from the group consisting of 1,5-D-anhydroglucitol, 1,5-D-anhydrofructose and derivatives thereof, and / or preventing postprandial hyperlipidemia and / or Or food with a label indicating that it is used for improvement, [13] A postprandial blood neutral fat elevation inhibitor comprising at least one selected from the group consisting of 1,5-D-anhydroglucitol, 1,5-D-anhydrofructose and derivatives thereof, and [14] A fat absorption inhibitor comprising at least one selected from the group consisting of 1,5-D-anhydroglucitol, 1,5-D-anhydrofructose and derivatives thereof.
  • composition for improving postprandial hyperglycemia and the composition for improving postprandial hyperlipidemia of the present invention have an effect of being able to quickly suppress a rapid increase in blood sugar level and blood triglyceride level caused by a meal. It is.
  • FIG. 1 is a diagram showing the results of hydrolysis of a 1,5-AG derivative with lipase.
  • FIG. 2 shows changes in blood glucose level when D-glucose or 1,5-AG is administered.
  • FIG. 3 shows changes in blood glucose level when D-glucose alone is administered alone and D-glucose and 1,5-AG are administered simultaneously.
  • FIG. 4 is a graph showing changes in blood triglyceride concentration when a fat emulsion alone is administered alone, and when a fat emulsion and 1,5-AG are administered simultaneously.
  • the present invention is greatly characterized in that 1,5-AG is used for suppressing an increase in blood glucose level and blood neutral fat level after eating.
  • fasting blood glucose level is less than 110 mg / dL
  • fasting blood triglyceride level is normal
  • blood sugar level and blood triglyceride level are temporary depending on diet Rises and then returns.
  • it is difficult to control blood sugar levels and blood triglyceride levels because they tend to fluctuate greatly depending on the content, amount, physical condition, etc. of the meal.
  • lifestyle-related diseases such as diabetes and hypertension develop, and risk of arteriosclerotic diseases such as myocardial infarction and stroke Becomes higher.
  • 1,5-AG is a safe compound without influencing hypoglycemia because it does not affect normal blood glucose during fasting.
  • postprandial hyperglycemia means a state in which the postprandial blood glucose level is abnormally high
  • postprandial hyperlipidemia means that the neutral fat level in the postprandial blood is abnormally high. It is a state where the value is high or usually returns to the original value in about 12 hours but does not return even if time passes.
  • the effect of suppressing an increase in blood glucose level after meals and blood neutral fat level by ingesting the composition of the present invention is not generally determined by the subject, but immediately after ingestion, preferably 1 minute.
  • the composition of the present invention is also a composition for preventing postprandial hyperglycemia and a composition for preventing postprandial hyperlipidemia.
  • the fasting blood glucose level is less than 126 mg / dL, and the blood glucose level of the 75 g oral glucose tolerance test is 140 to 199 mg / dL.
  • IGT impaired glucose tolerance
  • IFG fasting glycemic abnormalities
  • 1,5-AG is considered to be an effective preventive measure because it has an effect of suppressing an increase in blood triglyceride level after meals.
  • compositions for improving postprandial hyperglycemia and the composition for improving postprandial hyperlipidemia of the present invention are 1,5-D-anhydroglucitol, It contains at least one selected from the group consisting of 1,5-D-anhydrofructose and derivatives thereof.
  • 1,5-D-anhydroglucitol (1,5-AG) is a structure in which the 1-position of ⁇ -D-glucose is reduced, and is one of the most abundant polyols in the body.
  • 1,5-D-anhydrofructose (hereinafter also referred to as 1,5-AF) is reduced by NADPH-dependent reductase in vivo to produce 1,5-AG. Therefore, after ingesting 1,5-AF, it is converted into 1,5-AG in the body and the effects of the present invention are manifested. Similarly, the same can be said for the derivatives of 1,5-AG and 1,5-AF.
  • the derivatives of 1,5-AG and 1,5-AF are not particularly limited as long as they produce 1,5-AG in vivo.
  • R 1 , R 2 , R 3 and R 4 each independently represent a hydrogen atom, a saccharide, an amino acid, a vitamin, a vitamin-like substance or a fatty acid, provided that R 1 , R 2 , R 3 and R 4 are not simultaneously hydrogen atoms
  • a preferred example is a derivative of 1,5-AG represented by the formula:
  • R in formula (I) each independently represents a hydrogen atom, a saccharide, an amino acid, a vitamin, a vitamin-like substance or a fatty acid, provided that , R 1 , R 2 , R 3 and R 4 are not simultaneously hydrogen atoms.
  • saccharide examples include compounds having 3 to 7 carbon atoms such as aldose, ketose, alditol, deoxy sugar, anhydro sugar, amino sugar, inositol, aldonic acid, uronic acid, aldaric acid, carb sugar, thio sugar, imino sugar, aza sugar and the like.
  • disaccharides and polysaccharides comprising them as constituents may be either cyclic
  • the monosaccharide and disaccharide are ⁇ 1-2 bond, ⁇ 1-3 bond,
  • monosaccharides such as glucose, galactose, glucuronic acid, maltose, isomaltose, and lactose
  • disaccharides and polysaccharides containing them as constituent components are preferable from the viewpoint of degradability in vivo.
  • Derivatives having these saccharides include maltase, isomaltase, sucrase, lactase, cellobiase, trehalase and in vivo amylase, amyloglycosidase, glucosidase, mannosidase, galactosidase, fucosidase, glucuronidase, ⁇ - A series of enzymes such as glycosidase and ⁇ -glycosidase, lipase in digestive fluids such as gastric juice and pancreatic juice, amylase, or glucuronidase, galactosidase of intestinal bacteria, or hydrolyzed under physiological acidic conditions such as gastric acid 1,5 -Converted to AG.
  • the amino acids may be any of L-type amino acid residues, D-type amino acid residues, mixtures thereof, or derivatives thereof.
  • the amino acid may be any of ⁇ -amino acid, ⁇ -amino acid, ⁇ -amino acid and ⁇ -amino acid, with ⁇ -amino acid being preferred. Specific examples include glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, arginine, cystine, methionine, phenylalanine, tyrosine, tryptophan, histidine, proline and the like. . Derivatives having these amino acids are hydrolyzed in vivo by glycosidase, peptidase, esterase, etc., or hydrolyzed by exposure to physiological acidic or alkaline conditions in tissue cells to 1,5-AG. Converted.
  • Vitamins and vitamin-like active substances include vitamin A, vitamin B1 (thyamine, thiamine), vitamin B2 (riboflavin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B12 (cobalamin), vitamin C ( Examples include ascorbic acid), vitamin D, vitamin E, vitamin K, folic acid, niacin (vitamin B3, nicotinic acid), vitamin B17 (leitolyl, amygdalin), inositol, choline, vitamin F, flavonoids, and the like.
  • vitamins and derivatives with vitamin-like active substances are hydrolyzed by glycosidase, peptidase, esterase, etc. in the living body, or hydrolyzed by exposure to physiological acidic or alkaline conditions in tissue cells. Converted to 1,5-AG.
  • fatty acids having 2 to 20 carbon atoms such as octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, icosanoic acid and palmitic acid are preferable, and fatty acids having 8 to 20 carbon atoms are more preferable.
  • Derivatives having these fatty acids are hydrolyzed in vivo by various esterases such as pancreatic juice lipase, or hydrolyzed by exposure to physiological acidic or alkaline conditions in tissue cells. -Converted to AG.
  • saccharides, amino acids, vitamins, vitamin-like active substances or fatty acids can be converted into 1,5-AG in vivo as long as the sugars, amino acids, vitamins, vitamin-like active substances are used.
  • the fatty acid itself or a salt thereof may be used.
  • saccharides, amino acids, vitamins, vitamin-like substances or fatty acids as R 1 , R 2 , R 3 and R 4 mean residues bonded to 1,5-AG. .
  • 1,5-AG, 1,5-AF and derivatives thereof are commercially available products, but any method known in the art, for example, JP 2008-54531 A, J.JAm. Chem. Soc ., 72, 4547 (1950), J. Chem. Soc., 214 (1956) and the following methods may be used.
  • Examples of commercially available products include 1,5-anhydro-D-glucitol (manufactured by Wako Pure Chemical Industries).
  • 1,5-AG, 1,5-AF and their derivatives can be used alone or in combination of two or more, and the total content in the composition of the present invention is not particularly limited, and is usually 1 to 100 wt. %.
  • the form of the composition of the present invention is not particularly limited as long as at least one selected from the group consisting of 1,5-AG, 1,5-AF and derivatives thereof can be taken into the body.
  • forms in which 1,5-AG, 1,5-AF and derivatives thereof can be easily added to foods for example, powder form, granule form
  • tablet forms that can be ingested as supplements are exemplified.
  • a food containing the composition of the present invention that is, a food containing at least one selected from the group consisting of 1,5-AG, 1,5-AF and derivatives thereof, prevents and improves postprandial hyperglycemia.
  • the health functional food means the health functional food defined by the Ministry of Health, Labor and Welfare, and includes the nutrition functional food and the food for specified health.
  • the health functional food and the health food may be either food or beverage.
  • prevention and improvement means prevention and / or improvement.
  • a transient increase in blood glucose similar to postprandial hyperglycemia occurs. Since deterioration of blood glucose control in such a situation may be life threatening, blood glucose control is performed by insulin administration, diet therapy, oral medicine and the like. Since the composition of the present invention can also improve such an increase in blood glucose, the present invention also provides 1,5-D-anhydroglucitol, 1,5-D-anhydrofructose and derivatives thereof.
  • a food that contains at least one selected from the group consisting of and labeled to indicate that it is used for the prevention and / or improvement of hyperglycemia due to sugar intake other than oral.
  • composition of the present invention having the above form can be prepared according to a conventional method as long as it contains at least one selected from the group consisting of 1,5-AG, 1,5-AF and derivatives thereof. it can.
  • 1,5-AG, 1,5-AF and derivatives thereof can be used for other purposes such as those having a known postprandial hyperglycemia improving action or known postprandial hyperlipidemia amelioration It can also be prepared by blending with a component having an action.
  • the amount of intake of the composition of the present invention is appropriately set according to the form, method of intake, purpose of intake and age, weight, and symptoms of the subject of intake of the composition, but is preferably 1 mg or more / dose, for example. Listed as a quantity. Ingestion may be performed once or several times within a day within a desired intake range, but increases in-vivo 1,5-AG by ingestion to increase postprandial hyperglycemia and postprandial From the viewpoint of promptly improving the state of hyperlipidemia, the composition of the present invention is preferably taken before meals, after meals or simultaneously with foods.
  • postprandial blood triglyceride levels usually require about 4 to 8 hours to return to the original state (Tada Norio, “Postprandial Hyperlipidemia”, Clinical Medicine, Vol. 21, No. 2, 2005) and postprandial Since blood glucose levels may be similar, they may be taken before meals, after meals, between meals or simultaneously with foods. Further, from the viewpoint of promptly improving hyperglycemia at the time of non-oral sugar uptake such as infusion or dialysis, it may be taken immediately before, during or after uptake of non-oral sugar such as infusion or dialysis.
  • the intake period is arbitrary, and may be taken at the time of each meal, or when a high sugar-containing food or a high fat food is taken, it may be taken during infusion or dialysis.
  • food means foods and drinks whose blood sugar level and blood neutral fat level are increased by being provided and consumed mainly for food, such as salmon, gum, juice, etc. Includes sweets.
  • Before meal is the time from about 30 minutes before eating the food
  • After meal is the time from about 30 minutes after eating the food
  • Meal is about 2 hours after eating the food Means time.
  • “Ingestion” means “ingestion” and / or “administration”.
  • the ingestion subject of the present specification is preferably a human who needs an action to improve postprandial hyperglycemia or postprandial hyperlipidemia, but may be a pet animal or the like.
  • the present invention also provides at least one use selected from the group consisting of 1,5-AG, 1,5-AF and derivatives thereof for the manufacture of a preventive and / or ameliorating agent for postprandial hyperglycemia.
  • the present invention also relates to at least one compound selected from the group consisting of 1,5-AG, 1,5-AF and derivatives thereof for use in the prevention and / or improvement of postprandial hyperglycemia, postprandial hyperlipidemia
  • at least one compound selected from the group consisting of 1,5-AG, 1,5-AF and derivatives thereof for use in prevention and / or amelioration of symptoms.
  • the present invention also provides a method for preventing and / or improving postprandial hyperglycemia comprising the step of ingesting the subject of the composition of the present invention, and the prevention and / or improvement of postprandial hyperlipidemia comprising the step of ingesting the composition. Or provide an improvement method.
  • 1,5-AG can suppress an increase in blood glucose level and neutral fat level after meal
  • the present invention also provides 1,5-AG, 1,5-AF and derivatives thereof.
  • a postprandial blood neutral fat elevation inhibitor comprising at least one selected from the group consisting of:
  • the present invention provides a fat absorption inhibitor comprising at least one selected from the group consisting of 1,5-AG, 1,5-AF and derivatives thereof.
  • Example 1-1 Hydrolysis of 1,5-AG derivative with lipase
  • the lipase was derived from porcine pancreas (manufactured by Nacalai Tesque).
  • the enzyme protein was dissolved in 200 mM phosphate buffer (pH 7.5) to prepare an enzyme solution.
  • 1,5-anhydroglucitol-6-O-octanoic acid ester Synthesis Example 1
  • 1,5-anhydroglucitol-6-O-palmitic acid ester Synthesis Example 2
  • 200 ⁇ L of the enzyme solution was added to 500 ⁇ L of each fatty acid ester aqueous solution (50 mM), and incubated at 37 ° C.
  • the reaction was stopped by heating in a boiling water bath for 3 minutes, and the amount of 1,5-anhydroglucitol produced (1,5-AG amount) was quantified by HPLC. The results are shown in FIG. The amount of 1,5-AG when all the fatty acid esters were decomposed was defined as 100%.
  • FIG. 1 shows that 1,5-anhydroglucitol-6-O-octanoic acid ester and 1,5-anhydroglucitol-6-O-palmitic acid ester are in the presence of lipase derived from porcine pancreas.
  • lipase derived from porcine pancreas.
  • Example 1-2 Hydrolysis of 1,5-AG derivative with lipase
  • the lipase was derived from porcine pancreas (manufactured by Nacalai Tesque).
  • the enzyme protein was dissolved in 200 mM phosphate buffer (pH 7.5) to prepare an enzyme solution.
  • 1,5-anhydroglucitol-2,3,4,6-O-tetraacetate (Synthesis Example 3) and 1,5-anhydroglucitol-2,3,4,6- 200 ⁇ L of the enzyme solution was added to O-tetralaurate (Synthesis Example 4) and incubated at 37 ° C. for 180 minutes.
  • the reaction was stopped by heating in a boiling water bath for 3 minutes, and the amount of 1,5-anhydroglucitol produced (1,5-AG amount) was quantified by HPLC. The results are shown in Table 1. The amount of 1,5-AG when all the fatty acid esters were decomposed was defined as 100%.
  • Example 2-1 (Hydrolysis of 1,5-AG derivative by small intestine glycosidase)
  • the rat small intestine-derived glycosidase was prepared by preparing a small intestinal brush border membrane from the jejunum of Wistar male rats (10 weeks old, weight approximately 290-310 g) by the method of Kessler et al. (Kessler, M., Acuto, O. , Storelli, C., Murer, H., Muller, M. and Semenza, G. (1978) A modifild procedure for the rapid preparation of efeiciently transporting vesicles From Small Intestinal Brush Border Membranes, Bio. Bio. Acta, 506, 136 -154.).
  • 1-deoxy-maltose (4-O- ⁇ -D-glucopyranosyl-1,5-D-anhydroglucitol) and 1-deoxy-lactose (4-O- For ⁇ -D-galactopyranosyl-1,5-D-anhydroglucitol
  • 50 ⁇ L of 200 mM phosphate buffer (pH 6.8) to 20 ⁇ L of the enzyme solution obtained above, and continue at 37 ° C. for 30 minutes.
  • 50 ⁇ L of 100 mM of each sample was added and incubated at 37 ° C. for 30 minutes.
  • Example 2-2 Hydrolysis of 1,5-AG derivative by small intestine glycosidase 50 ⁇ L of 200 mM phosphate buffer (pH 6.8) was added to 20 ⁇ L of rat small intestine-derived glycosidase obtained in the same manner as in Example 2-1, followed by preincubation at 37 ° C. for 30 minutes, and then 100 mM 1-deoxy-isomalt. 50 ⁇ L of triose (Synthesis Example 6) was added and incubated at 37 ° C. The reaction was stopped by heating in a boiling water bath for 3 minutes. The liberated 1,5-AG in the reaction solution was quantified by analyzing with HPLC (column; HITACHI GL-C611). The results are shown in Table 3.
  • Example 2-3 hydrolysis of 1,5-AG derivative by small intestinal glycosidase and lipase
  • 100 ⁇ L of an enzyme solution of porcine pancreatic lipase (manufactured by Nacalai Tesque) obtained in the same manner as in Example 1-1 and 100 ⁇ L of rat small intestine-derived glycosidase obtained in the same manner as in Example 2-1 were added to 100 mM phosphate buffer.
  • the solution (pH 6.8) was dissolved in 100 ⁇ L.
  • 1-deoxy-isomaltotriose-decaacetate (Synthesis Example 5) was added to 200 ⁇ L of this enzyme mixed solution and incubated at 37 ° C. for 180 minutes. The reaction was stopped by heating in a boiling water bath for 3 minutes.
  • Example 3 Influence of 1,5-AG on fasting blood glucose Seven-week-old ddy male mice fasted overnight (purchased from Japan SLC, Inc., average body weight 30 g), water for injection containing D-glucose or 1,5-AG (manufactured by Otsuka Pharmaceutical Co., Ltd.), Each was administered orally in a gastric thanke so that the body weight was 2.5 g / kg (5 animals per group). Blood was collected from the tail vein at 15, 30, 60 and 120 minutes after administration, and the blood glucose level was measured. The blood glucose level was measured with Antsense III (manufactured by Bayer Medical). The results are shown in FIG.
  • Example 4 (Effect of 1,5-AG on postprandial blood glucose) 7-week-old ddy male mice fasted overnight (purchased from Japan SLC, Inc., average body weight 30 g), water for injection containing D-glucose or D-glucose and 1,5-AG (Otsuka Pharmaceutical Co., Ltd.) ), 2.5 g / kg body weight for the D-glucose single administration group, D-glucose 2.5 g / kg body weight, 1,5-AG 250 mg / kg body weight for the combination group 1 of D-glucose and 1,5-AG In combination group 2, D-glucose 2.5 g / kg body weight and 1,5-AG 500 mg / kg body weight were orally administered by gastric thanke (5 mice in each group).
  • Example 5 (Effect of 1,5-AG on postprandial blood neutral fat) A 12-week old Wistar male rat fasted overnight (purchased from Japan SLC, Inc., average body weight 310 g), only 2.0 g / kg body weight of fat emulsion (Intralipid (registered trademark), manufactured by Otsuka Pharmaceutical Co., Ltd.) The fat emulsion and 1,5-AG were administered orally in a gastric thanke at the same time so that the fat emulsion was 2.0 g / kg body weight and 1,5-AG 500 mg / kg body weight. 5 animals in each group). Blood was collected from the tail vein at 120, 180, 240 and 300 minutes after administration, and the blood neutral fat (blood triglyceride) concentration was measured as blood neutral fat.
  • blood neutral fat blood triglyceride
  • the blood triglyceride concentration was quantified with Triglyceride E-Test Wako (Wako Pure Chemical Industries, Ltd.). The results are shown in FIG. In the figure, “*” indicates that there is a significant difference (p ⁇ 0.05).
  • Reference Example 1 (Acute toxicity test with a single administration of 1,5-AG) Three mice (6 weeks old ddy male mice, purchased from Japan SLC, Inc.) were orally administered at 10 g / kg body weight, which is considered to be the maximum dose that can be administered at one time. As a result, all three animals survived, and no changes were observed in organs, behavior and the like.
  • composition for improving postprandial hyperglycemia and the composition for improving postprandial hyperlipidemia of the present invention are intended to improve the above symptoms in people who have symptoms or symptoms of postprandial hyperglycemia or postprandial hyperlipidemia. Is preferably used.

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Abstract

La présente invention porte sur une composition destinée à améliorer l'hyperglycémie postprandiale, qui contient au moins un élément choisi dans le groupe constitué par le 1,5-D-anhydroglucitol, le 1,5-D-anhydrofructose et leurs dérivés. L'invention porte également sur une composition destinée à améliorer l'hyperlipémie postprandiale, qui contient au moins un élément choisi dans le groupe constitué par le 1,5-D-anhydroglucitol, le 1,5-D-anhydrofructose et leurs dérivés. La composition susmentionnée, destinée à améliorer l'hyperglycémie postprandiale et la composition destinée à améliorer l'hyperlipémie postprandiale sont utilisables de façon appropriée pour soulager les symptômes de l'hyperglycémie postprandiale et de l'hyperlipémie postprandiale chez les personnes qui présentent des symptômes ou des signes de ces affections.
PCT/JP2010/050551 2009-01-19 2010-01-19 Composition contenant 1,5-ag WO2010082661A1 (fr)

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Publication number Priority date Publication date Assignee Title
JP2011037806A (ja) * 2009-08-18 2011-02-24 Toyama Univ 口腔用組成物
JP2012001515A (ja) * 2010-06-21 2012-01-05 Toyama Univ グリコーゲン分解酵素阻害剤
WO2012055010A1 (fr) * 2010-10-25 2012-05-03 Fédération Des Producteurs Acéricoles Du Québec Produits issus de l'érable, et leur utilisation
JP2013203707A (ja) * 2012-03-29 2013-10-07 Nihon Starch Co Ltd １，５−ｄ−アンヒドロフルクトースからなる抗肥満作用剤
WO2014171279A1 (fr) * 2013-04-15 2014-10-23 国立大学法人富山大学 Accélérateur de production de collagène contenant du 1,5-anhydro-d-glucitol

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011037806A (ja) * 2009-08-18 2011-02-24 Toyama Univ 口腔用組成物
JP2012001515A (ja) * 2010-06-21 2012-01-05 Toyama Univ グリコーゲン分解酵素阻害剤
WO2012055010A1 (fr) * 2010-10-25 2012-05-03 Fédération Des Producteurs Acéricoles Du Québec Produits issus de l'érable, et leur utilisation
JP2013203707A (ja) * 2012-03-29 2013-10-07 Nihon Starch Co Ltd １，５−ｄ−アンヒドロフルクトースからなる抗肥満作用剤
WO2014171279A1 (fr) * 2013-04-15 2014-10-23 国立大学法人富山大学 Accélérateur de production de collagène contenant du 1,5-anhydro-d-glucitol
CN105120861A (zh) * 2013-04-15 2015-12-02 国立大学法人富山大学 含有1,5-脱水-d-葡糖醇的胶原产生促进剂
JP6045688B2 (ja) * 2013-04-15 2016-12-14 国立大学法人富山大学 １，５−アンヒドロ−ｄ−グルシトール含有コラーゲン産生促進剤

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