WO2020137659A1 - Composition for suppressing increases in blood sugar level/for suppressing increases in blood triglycerides - Google Patents

Composition for suppressing increases in blood sugar level/for suppressing increases in blood triglycerides Download PDF

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WO2020137659A1
WO2020137659A1 PCT/JP2019/049186 JP2019049186W WO2020137659A1 WO 2020137659 A1 WO2020137659 A1 WO 2020137659A1 JP 2019049186 W JP2019049186 W JP 2019049186W WO 2020137659 A1 WO2020137659 A1 WO 2020137659A1
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extract
composition
blood glucose
suppressing
chitosan
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PCT/JP2019/049186
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French (fr)
Japanese (ja)
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喜子 久保田
香央 迫田
侑里 竹下
武田 守
▲徳▼人 島津
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株式会社ファンケル
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Priority to CN201980074183.2A priority Critical patent/CN112996523A/en
Publication of WO2020137659A1 publication Critical patent/WO2020137659A1/en

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L2/00Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716Glucans
    • A61K31/722Chitin, chitosan
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/60Moraceae (Mulberry family), e.g. breadfruit or fig
    • A61K36/605Morus (mulberry)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/82Theaceae (Tea family), e.g. camellia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in blood triglyceride, which comprises a tea flower extract, a mulberry leaf extract, and chitosan as active ingredients.
  • Obesity has been high since the middle ages, and statistics have been obtained that 30% or more of men in their 40s and 70s and 20-30% of women are obese. Obesity has been identified as increasing the risk of these diseases including the three major causes of death of cancer, heart disease and cerebrovascular disease. Obesity is caused by excessive intake of carbohydrates and increased intake of greasy sweets and sweet drinks. Although “dietary guidelines” and “dietary balance guides” have been established for the purpose of improving such eating habits, it is difficult to change eating habits. Therefore, diet supplements are widely used as dietary supplements.
  • active ingredients that can be added to dietary supplements include chitosan, which has a glucose absorption inhibitory effect for the purpose of suppressing postprandial blood glucose elevation, and mulberry extract, which suppresses the decomposition of sugars such as starch.
  • Patent Document 1 describes a diet food containing mulberry leaf extract and chitosan as useful ingredients.
  • Mulberry leaf extract inhibits the rise of blood glucose by inhibiting ⁇ -glucosidase in the digestive tract and inhibiting the decomposition of starch into glucose.
  • Chitosan is known to have an ⁇ -glucosidase inhibitory action and an ⁇ -amylase inhibitory action in addition to suppressing the absorption of sugars by adhering to the mucosa in the digestive tract.
  • tea flower extract contains flavonoid glycosides peculiar to tea flowers and improves fat metabolism (Patent Document 2).
  • Patent Document 3 describes a technique for extracting tea saponin from tea flowers.
  • saponin contained in tea flowers has antiallergic activity (Patent Document 4), neutral fat absorption suppression/gastric mucosal protection/sugar absorption suppression (Patent Document 5) intestinal motility enhancing action, intestinal obstruction or constipation prevention/improvement action.
  • Various pharmacological actions such as pancreatic lipase activity inhibitory action/free fatty acid production inhibitory action (Patent Document 6) and gastric emptying function inhibitory action (Patent Document 7) are known.
  • JP 2004-194635 A JP, 2011-051950, A JP, 2005-166326, A Japanese Patent Laid-Open No. 2008-024654 JP 2006-070018 A JP, 2009-057365, A JP, 2009-249374, A
  • the present inventors have found that a composition containing three components of a mulberry leaf extract, chitosan, and a tea flower extract has an unprecedented strong inhibitory effect on postprandial blood glucose level elevation and blood triglyceride elevation, and the present invention has been completed. did.
  • an object of the present invention is to provide a novel composition for suppressing an increase in postprandial blood glucose level and a composition for suppressing an increase in blood triglyceride.
  • the main configuration of the present invention is as follows.
  • a composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride which comprises tea flower extract, mulberry leaf extract, and chitosan as active ingredients.
  • the composition according to (1) which contains 2 to 4 parts by mass of dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract.
  • the composition according to (1) or (2) which is to be taken just before ingesting a meal.
  • a composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride comprising 25 to 500 mg of a dried tea flower extract, 50 to 1000 mg of a dried product of mulberry leaf extract, and 25 to 1000 mg of chitosan.
  • the present invention provides a new composition for suppressing an increase in postprandial blood glucose level, a tablet and a food or drink containing the same.
  • the composition of the present invention exerts the action and effect of lowering the blood glucose level which rises after eating. In humans, it also suppresses postprandial blood triglyceride elevation. Therefore, it can be used as a diet supplement or the like.
  • TG blood triglyceride
  • the present invention is an invention of a composition for suppressing an increase in postprandial blood glucose level, which contains tea flower extract, mulberry leaf extract, and chitosan as active ingredients, and a tablet for suppressing an increase in postprandial blood glucose level and a food or drink containing the composition.
  • the tea flower used is a flower part of tea (Camellia sinensis), also known as Thea sinensis, which belongs to the genus Camellia L. , So-called flowers including flower stems, floral patterns, flower buds and buds.
  • the tea flowers can be used as they are, as they are collected, or after they are dried, or after being made into tea by a method known to those skilled in the art.
  • the tea flower extract in the present invention means an extract obtained by extracting the tea flower with water or an aqueous organic solvent and then removing the solvent, or an extract obtained by partitioning and extracting the tea flower with an aqueous solvent.
  • the methods disclosed in Patent Documents 3 to 7 can be used. Specifically, it is as described below.
  • lower alcohol is preferable as the above-mentioned aqueous organic solvent.
  • the lower alcohol include alcohols having 1 to 4 carbon atoms. Specific examples thereof include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol or t-butanol, a mixed solution thereof, and a hydrous alcohol in any proportion thereof. Water or ethanol is preferably used.
  • water or about 80% ethanol is used, but in the present invention, the amount of ethanol in the hydrous ethanol is not particularly limited to 80%.
  • These extraction solvents are used in an amount of about 1 to 50 times (volume), preferably about 2 to 10 times (volume) of the extraction material.
  • the extraction can be performed while hot or at room temperature, and the extraction temperature can be arbitrarily set between room temperature and the boiling point of the solvent.
  • hot extraction it is carried out, for example, by immersing the inflorescence part of the tea flower in the above extraction solvent at a temperature of 50° C. to the boiling point of the extraction solvent with or without shaking (or stirring) or under reflux. Is appropriate.
  • the extraction material is immersed in shaking, it is suitable to carry out for 30 minutes to 5 hours, and when it is immersed in non-shaking, it is suitable to carry out for 1 hour to 20 days. Further, when performing extraction under reflux of the extraction solvent, it is preferable to heat and reflux for 30 minutes to several hours.
  • the extraction operation may be performed only once for the same material, but it is preferable to repeat the extraction operation a plurality of times, for example, about 2 to 5 times, from the viewpoint of extraction efficiency.
  • the extract obtained by filtering the solid matter after filtration is concentrated by a conventional method to obtain an extract. Concentration is preferably performed under reduced pressure. Concentration may be performed until the extract is dried.
  • the extract may be used as it is for preparing the composition of the present invention, or may be used in the present invention as a powdery or lyophilized dry extract product or the like. As a method for making these solids, a method known in the art can be adopted.
  • the tea flower extract in the present invention includes a concentrated dried product or a lyophilized product. Further, in the present invention, the extract obtained by concentrating the tea flower extract is subjected to partition extraction with a solvent, that is, partition extraction using water and a non-hydratable organic solvent, once or multiple times to obtain an organic solvent-soluble fraction. And water-soluble fraction.
  • a solvent that is, partition extraction using water and a non-hydratable organic solvent
  • non-hydratable organic solvent examples include ethyl acetate, n-butanol, hexane, chloroform and the like, among which ethyl acetate is preferable. That is, the extract obtained by concentrating the water or hydrous lower alcohol extract of tea flowers is distributed with ethyl acetate and water as necessary to obtain an ethyl acetate-soluble fraction and a water-soluble fraction. You can
  • the water-soluble fraction obtained above can be further subjected to partition extraction using water and a non-hydratable organic solvent to separate it as an organic solvent-soluble fraction and a water-soluble fraction.
  • the non-hydratable organic solvent in this case include n-butanol, hexane, chloroform and the like, among which n-butanol is preferable. That is, the water-soluble fraction obtained after the partition between ethyl acetate and water is directly subjected to partition with n-butanol, or the residue obtained by concentrating the water-soluble fraction is further mixed with water and n-butanol. Then, the n-butanol fraction and the water-soluble fraction can be obtained.
  • Tea extract is also commercially available as a raw material for supplements, and this commercially available tea extract can be used for the purpose of the present invention.
  • Examples of such commercially available tea flower extract include "tea flower dried extract (manufactured by Japan Medicinal Food Research Institute Co., Ltd.)".
  • tea flower extract used in the present invention it is preferable that the tea flower extract contains tea flower saponins in an amount of 1.5% by mass or more as a total saponin.
  • the tea extract is added as a dried extract so that the composition of the present invention contains 25 to 500 mg, preferably 50 to 250 mg, per person.
  • Mulberry leaves are leaves of the mulberry genus of the mulberry family, and have been used for a long time as tea as well as for feeding silkworms.
  • Typical examples of plants generally called mulberry are Yamaguchi (M. bombycis), Nagamiguwa (M. laevigata), and Keguwa (M. tiliaefolia).
  • the mulberry leaf extract may be a commercially available product, and is commercially available from Nippon Shinyaku Co., Ltd., Toyoda Fragrance Co.
  • the mulberry leaf extract is preferably a hot water extract or a hydrous ethanol extract.
  • fresh or dried leaves of mulberry leaves are shredded, extracted in hot water for 15 minutes or more, and then concentrated and dried to obtain a powder.
  • the mulberry leaf extract is not limited to the above-mentioned powdery substance, and a concentrated liquid substance obtained without drying, a liquid extract obtained without concentration and the like can be used.
  • the mulberry leaf extract is blended as an extract dried product so that the composition of the present invention contains 50 to 1000 mg, preferably 100 to 500 mg, per person.
  • Chitosan is a kind of polysaccharide, poly- ⁇ 1 ⁇ 4-glucosamine. It is a linear polysaccharide, a 1,4-polymer of glucosamine, which is a high molecular weight substance with a molecular weight of several thousand to several hundred thousand.
  • Examples of chitosan used in the present invention include those obtained from cell walls such as crab, shrimp carapace, insect shell, squid, mushroom and filamentous fungi. Those obtained from the crust of shrimp and shrimp are preferable.
  • Chitosan is composed of glucosamine and acetylglucosamine and is soluble in acidic water.
  • the average molecular weight is usually 10,000 or more, but preferably the average molecular weight is 100,000 or more and the rotational viscosity is 20 mPa ⁇ s or more. And more preferably, the average molecular weight is 800,000 or more and the rotational viscosity is 100 mPa ⁇ s or more.
  • the particle size of chitosan is not particularly limited, but is preferably 30 mesh pass or less, more preferably 80 mesh pass or less. Chitosan is commercially available as a raw material for diet foods, and for example, a product of Nippon Kayaku Food Techno Co., Ltd. can be used. Chitosan is added to the composition of the present invention so as to be contained in an amount of 25 to 1000 mg, preferably 50 to 500 mg per person.
  • composition of the present invention is blended so as to contain 2 to 4 parts by mass of dried matter of mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract. With such a blending ratio, an effective postprandial blood glucose level increase suppressing action is exhibited.
  • a known combination of mulberry leaf extract and chitosan exhibits a postprandial blood glucose level elevation-inhibiting effect of a level known in the prior art.
  • the inventors of the present invention tested a tea flower extract known to have an inhibitory effect on blood sugar level elevation, they did not exhibit an inhibitory effect on postprandial blood glucose level elevation in animal tests.
  • composition containing the three components of tea flower extract, mulberry leaf extract, and chitosan showed an excellent inhibitory effect on postprandial blood glucose level elevation. Therefore, the composition containing the three components of the tea flower extract, mulberry leaf extract, and chitosan exerts an unprecedented strong effect of suppressing the increase in postprandial blood glucose level.
  • composition of the present invention may be added to foods and beverages, and it is preferable to take it at the timing of eating.
  • composition of the present invention can be incorporated into health foods or supplement tablets as it is or after being formulated.
  • excipients and other active ingredients can be used within a range that does not impair the purpose of the composition of the present invention.
  • Animal test for confirming the postprandial blood glucose elevation suppression effect > 1. Animals to be used ddy mice, 8 weeks old at the start of the test, 40 males were purchased, and their weights were measured, and each group was divided into 5 groups, with 8 mice per group. After carrying in the animals, a acclimation period was set to about one week, and the animals were fasted for 12 hours or more from the evening of the last day of the acclimation period.
  • mice were forcibly orally administered with a solution of the test substance dissolved in distilled water at 5 mL/kg, and then similarly forcibly orally administered with sugar (sucrose) at 2 g/5 mL/kg.
  • Test substance The administration group and dose of the test substance are as follows. (1) Control (distilled water 5 mL/kg) (2) Chitosan 66.6 mg/kg+mulberry leaf extract (described as “mulberry” in the figure) 133.44 mg/kg (3) Tea flower extract (described as “Chaka” in the figure) 39.96 mg/kg (4) Chitosan 66.6 mg/kg+mulberry leaf extract 133.44 mg/kg+tea flower extract 39.96 mg/kg (5) Positive control (Posicon) Acarbose 10 mg/kg Acarbose, which was used as a positive control, is a drug for the treatment of diabetes that inhibits digestive enzymes required for digesting carbohydrates, especially ⁇ -glucosidase secreted from the small intestine and ⁇ -amylase secreted from the pancreas, and increases postprandial blood glucose levels. Known to suppress. The above-mentioned amounts of chitosan, mulberry leaf extract and tea flower extract were calculated and
  • Test meal (1) Test meal Tablets formed by tablet compression (CAL) (1 dose 3 tablets) Mulberry leaf extract (dry matter) 200mg Chitosan 100mg Tea flower extract (dry product) 60mg Is compounded. In addition, the following ingredients were added as excipients to produce tablets. Cellulose, starch, hydroxypropyl cellulose, silicon dioxide, calcium stearate, shellac, uncalcined shell calcium, colorant (placebo only), cellulose, starch, calcium monohydrogen phosphate, calcium stearate, shellac.
  • Carbohydrate load The subject ingests 200 g of retort cooked rice (trade name of "Sato no rice") as a sugar load after ingesting a test meal or a placebo.
  • the nutritional components of cooked rice are as follows.
  • test food For carbohydrate loading, after fasting blood sampling, ingest the test food with 150 mL of water, and 10 minutes later, ingest 200 g of “rice sugar” with 150 mL of water for 10 minutes.
  • Blood is collected at 30, 60, and 120 minutes after the start of ingestion of cooked rice.
  • the test was divided into stage I and stage II, and the subject was a crossover test in which both the test meal and the placebo were ingested (a blank period of 4 days or more was set).
  • the blood samples collected were measured for blood glucose level and insulin level.
  • Fig. 5 shows a graph of blood glucose measurement results
  • Fig. 6 shows a graph of insulin measurement results.
  • Fig. 7 shows a graph of the measurement result of triglyceride.
  • the test food (CAL) was ingested
  • the blood triglyceride level after 2, 3, 4 and 6 hours of lipid loading and the AUC up to 6 hours after administration of the placebo (P) were significantly lower. Therefore, it was confirmed that the composition of the present invention suppresses an increase in postprandial blood glucose level in humans.
  • the clinical tests (1) and (2) there was no problem in the health of the subject.

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Abstract

The present invention addresses the problem of providing a novel composition for suppressing post-meal increases in blood sugar level and/or for suppressing post-meal increases in blood triglycerides. Provided is a composition for suppressing post-meal increases in blood sugar level and/or for suppressing post-meal increases in blood triglycerides that contains tea flower extract, mulberry leaf extract, and chitosan as active ingredients.

Description

血糖値上昇抑制用、血中トリグリセリド上昇抑制用組成物Composition for suppressing increase in blood glucose level and suppressing increase in blood triglyceride
 本発明は、茶花抽出物、桑の葉抽出物、キトサンを有効成分として含有する食後血糖値上昇抑制用及び/また血中トリグリセリド上昇抑制用組成物に関する。 The present invention relates to a composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in blood triglyceride, which comprises a tea flower extract, a mulberry leaf extract, and chitosan as active ingredients.
 肥満は中年以降に多く、40-70代の男性で30%以上、女性では20-30%が肥満であるとの統計結果が得られている。肥満は、ガン、心臓病、脳血管障害のいわゆる3大死因を含めたこれらの疾患のリスクを上げることが確認されている。肥満は、炭水化物の過剰摂取や、脂っこく甘い菓子、甘い飲料の摂取量の増加が原因とされる。このような食生活を改善することを目的として「食生活指針」や「食事バランスガイド」などが策定されているが、食習慣を変更することは困難である。
 このため健康補助食品として、ダイエット用サプリメントが広く利用されている。ダイエット用サプリメントに配合される有効成分としては、食後血糖の上昇を抑制する目的でグルコース吸収抑制作用を有するキトサンや、デンプンなど糖質類の分解を抑制する桑抽出物などあげられる。
Obesity has been high since the middle ages, and statistics have been obtained that 30% or more of men in their 40s and 70s and 20-30% of women are obese. Obesity has been identified as increasing the risk of these diseases including the three major causes of death of cancer, heart disease and cerebrovascular disease. Obesity is caused by excessive intake of carbohydrates and increased intake of greasy sweets and sweet drinks. Although "dietary guidelines" and "dietary balance guides" have been established for the purpose of improving such eating habits, it is difficult to change eating habits.
Therefore, diet supplements are widely used as dietary supplements. Examples of active ingredients that can be added to dietary supplements include chitosan, which has a glucose absorption inhibitory effect for the purpose of suppressing postprandial blood glucose elevation, and mulberry extract, which suppresses the decomposition of sugars such as starch.
 特許文献1には、桑の葉エキスとキトサンを有用成分として含有するダイエット用食品が記載されている。桑の葉エキスは消化管内のα-グルコシダーゼを阻害してデンプンからグルコースへの分解を抑制することで血中グルコースの上昇を抑制する。キトサンは、消化管内粘膜に粘着することで糖質の吸収を抑制する他、α-グルコシダーゼ阻害作用、α-アミラーゼ阻害作用が知られている。 Patent Document 1 describes a diet food containing mulberry leaf extract and chitosan as useful ingredients. Mulberry leaf extract inhibits the rise of blood glucose by inhibiting α-glucosidase in the digestive tract and inhibiting the decomposition of starch into glucose. Chitosan is known to have an α-glucosidase inhibitory action and an α-amylase inhibitory action in addition to suppressing the absorption of sugars by adhering to the mucosa in the digestive tract.
 また近年ダイエットの有用成分として茶花抽出物の作用が注目されている。茶花エキスには、茶花特有のフラボノイド配糖体が含有されており脂肪代謝を改善する(特許文献2)。 In recent years, the action of tea flower extract has attracted attention as a useful component of diet. The tea flower extract contains flavonoid glycosides peculiar to tea flowers and improves fat metabolism (Patent Document 2).
 特許文献3には、茶花からティーサポニンを抽出する技術が記載されている。また茶花に含有されるサポニンは、抗アレルギー活性(特許文献4)、中性脂肪吸収抑制・胃粘膜保護・糖吸収抑制(特許文献5)腸運動亢進作用・腸閉塞又は便秘の予防もしくは改善作用・膵リパーゼ活性阻害作用・遊離脂肪酸産生抑制作用(特許文献6)および胃排出機能抑制作用(特許文献7)など様々な薬理作用が公知である。 Patent Document 3 describes a technique for extracting tea saponin from tea flowers. In addition, saponin contained in tea flowers has antiallergic activity (Patent Document 4), neutral fat absorption suppression/gastric mucosal protection/sugar absorption suppression (Patent Document 5) intestinal motility enhancing action, intestinal obstruction or constipation prevention/improvement action. Various pharmacological actions such as pancreatic lipase activity inhibitory action/free fatty acid production inhibitory action (Patent Document 6) and gastric emptying function inhibitory action (Patent Document 7) are known.
特開2004-194635号公報JP 2004-194635 A 特開2011-051950号公報JP, 2011-051950, A 特開2015-166326号公報JP, 2005-166326, A 特開2008-024654号公報Japanese Patent Laid-Open No. 2008-024654 特開2006-070018号公報JP 2006-070018 A 特開2009-057365号公報JP, 2009-057365, A 特開2009-249374号公報JP, 2009-249374, A
 本発明者らは、桑の葉抽出物、キトサン、茶花抽出物の3成分を含有する組成物に従来にない強い食後血糖値上昇抑制作用と血中トリグリセリド上昇抑制作用を見出し、本発明をなした。 The present inventors have found that a composition containing three components of a mulberry leaf extract, chitosan, and a tea flower extract has an unprecedented strong inhibitory effect on postprandial blood glucose level elevation and blood triglyceride elevation, and the present invention has been completed. did.
 すなわち、本発明の課題は、新規な食後血糖値上昇抑制用組成物及び血中トリグリセリド上昇抑制用組成物を提供することにある。 That is, an object of the present invention is to provide a novel composition for suppressing an increase in postprandial blood glucose level and a composition for suppressing an increase in blood triglyceride.
 本発明の主な構成は、以下の通りである。
(1)茶花エキス、桑の葉エキス、及びキトサンを有効成分として含有する食後血糖値上昇抑制用及び/または食後血中トリグリセリド上昇抑制用組成物。
(2)茶花エキス乾燥物1質量部当たり桑の葉エキス乾燥物2~4質量部、キトサン1~2質量部を含有する(1)に記載の組成物。
(3)食事摂取直前に飲用するための(1)または(2)に記載の組成物。
(4)茶花エキス乾燥物として25~500mg、桑の葉エキス乾燥物として50~1000mg、キトサン25~1000mgを含有する食後血糖値上昇抑制用及び/または食後血中トリグリセリド上昇抑制用組成物。
The main configuration of the present invention is as follows.
(1) A composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride, which comprises tea flower extract, mulberry leaf extract, and chitosan as active ingredients.
(2) The composition according to (1), which contains 2 to 4 parts by mass of dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract.
(3) The composition according to (1) or (2), which is to be taken just before ingesting a meal.
(4) A composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride, comprising 25 to 500 mg of a dried tea flower extract, 50 to 1000 mg of a dried product of mulberry leaf extract, and 25 to 1000 mg of chitosan.
 本発明により新たな食後血糖値上昇抑制用組成物及びそれを含有する錠剤や飲食品が提供される。本発明の組成物は、食後上昇する血糖値を低下させる作用効果を発揮する。またヒトにあっては、食後の血中トリグリセリドの上昇も抑制する。このためダイエット用サプリメント等に使用することができる。 INDUSTRIAL APPLICABILITY The present invention provides a new composition for suppressing an increase in postprandial blood glucose level, a tablet and a food or drink containing the same. The composition of the present invention exerts the action and effect of lowering the blood glucose level which rises after eating. In humans, it also suppresses postprandial blood triglyceride elevation. Therefore, it can be used as a diet supplement or the like.
動物試験における試験動物の血中グルコース濃度の経時変化を示すグラフである。It is a graph which shows the time-dependent change of the blood glucose level of the test animal in an animal test. 動物試験における試験動物の血中グルコース濃度のΔ経時変化を示すグラフである。It is a graph which shows the time-dependent change of the blood glucose level of the test animal in an animal test. 動物試験における試験動物の血中グルコース濃度のAUCを示すグラフである。It is a graph which shows AUC of the blood glucose level of the test animal in an animal test. 動物試験における試験動物の血中グルコース濃度のΔAUCを示すグラフである。It is a graph which shows (DELTA)AUC of the blood glucose level of the test animal in an animal test. ヒト臨床試験(1)における血糖値経時変化を示すグラフである。It is a graph which shows a time-dependent change in blood glucose level in a human clinical test (1). ヒト臨床試験(1)における血中インスリン値の経時変化を示すグラフである。It is a graph which shows the time-dependent change of the blood insulin level in a human clinical test (1). ヒト臨床試験(2)における血中トリグリセリド(TG)値の経時変化を示すグラフである。It is a graph which shows the time-dependent change of the blood triglyceride (TG) value in a human clinical test (2).
 本発明は、茶花エキス、桑の葉エキス、及びキトサンを有効成分として含有する食後血糖値上昇抑制用組成物およびこれを含有する食後血糖値上昇抑制用錠剤や飲食品の発明である。
 本発明において、用いられる茶花とは、ツバキ科 (Theaceae)植物ツバキ属 (Camellia L.)に属する茶 (Camellia sinensis、別名Thea sinensis)の花部、すなわち、雌しべ、雄しべ、花弁、萼、苞葉、花軸、花柄等を含むいわゆる花、花芽および蕾などを意味する。
 本発明において、茶花は、採取したものをそのまま、または乾燥して、あるいは当業者に公知の方法で製茶して用いることができる。
The present invention is an invention of a composition for suppressing an increase in postprandial blood glucose level, which contains tea flower extract, mulberry leaf extract, and chitosan as active ingredients, and a tablet for suppressing an increase in postprandial blood glucose level and a food or drink containing the composition.
In the present invention, the tea flower used is a flower part of tea (Camellia sinensis), also known as Thea sinensis, which belongs to the genus Camellia L. , So-called flowers including flower stems, floral patterns, flower buds and buds.
In the present invention, the tea flowers can be used as they are, as they are collected, or after they are dried, or after being made into tea by a method known to those skilled in the art.
(茶花エキス)
 本発明でいう茶花エキスとは前記の茶花を水または水性有機溶媒で抽出した後、溶媒を除いた抽出物、あるいはこれをさらに水性溶媒を用いて分配抽出した抽出物をいう。
(Tea extract)
The tea flower extract in the present invention means an extract obtained by extracting the tea flower with water or an aqueous organic solvent and then removing the solvent, or an extract obtained by partitioning and extracting the tea flower with an aqueous solvent.
 茶花エキスを製造するための抽出技術は、特許文献3~7に開示される方法を使用することができる。具体的には次に記載のとおりである。
 本発明の茶花エキスの製造に用いられる抽出溶媒に関して、上記の水性有機溶媒として低級アルコールが好ましい。低級アルコールとしては、炭素数1~4のアルコール類が挙げられる。具体的には、メタノール、エタノール、n-プロパノール、イソプロパノール、n-ブタノール、イソブタノールもしくはt-ブタノールまたはこれらの混液あるいはこれらの任意の割合における含水アルコール等が挙げられる。好ましくは、水またはエタノールが用いられる。さらに好ましくは、水または約80%エタノールが用いられるが、本発明においては、含水エタノールのエタノール量が特に80%に限定されるものではない。
 これらの抽出用溶媒は、抽出材料に対して1~50倍 (容量)程度、好ましくは2~10倍(容量)程度用いられる。
As the extraction technique for producing a tea flower extract, the methods disclosed in Patent Documents 3 to 7 can be used. Specifically, it is as described below.
Regarding the extraction solvent used for producing the tea flower extract of the present invention, lower alcohol is preferable as the above-mentioned aqueous organic solvent. Examples of the lower alcohol include alcohols having 1 to 4 carbon atoms. Specific examples thereof include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol or t-butanol, a mixed solution thereof, and a hydrous alcohol in any proportion thereof. Water or ethanol is preferably used. More preferably, water or about 80% ethanol is used, but in the present invention, the amount of ethanol in the hydrous ethanol is not particularly limited to 80%.
These extraction solvents are used in an amount of about 1 to 50 times (volume), preferably about 2 to 10 times (volume) of the extraction material.
 なお、抽出は、熱時または室温で行うことができ、抽出温度は、室温と溶媒の沸点の間で任意に設定できる。熱時抽出の場合、例えば、50℃~抽出溶媒の沸点の温度で、振盪(または撹拌)下もしくは非振盪下または還流下に、茶花の花部を上記の抽出溶媒に浸漬することによって行うのが適当である。抽出材料を振盪下に浸漬する場合には、30分間~5時間程度行うのが適当であり、非振盪下に浸漬する場合には、1時間~20日間程度行うのが適当である。また、抽出溶媒の還流下に抽出するときは、30分~数時間加熱還流することが好ましい。 Note that the extraction can be performed while hot or at room temperature, and the extraction temperature can be arbitrarily set between room temperature and the boiling point of the solvent. In the case of hot extraction, it is carried out, for example, by immersing the inflorescence part of the tea flower in the above extraction solvent at a temperature of 50° C. to the boiling point of the extraction solvent with or without shaking (or stirring) or under reflux. Is appropriate. When the extraction material is immersed in shaking, it is suitable to carry out for 30 minutes to 5 hours, and when it is immersed in non-shaking, it is suitable to carry out for 1 hour to 20 days. Further, when performing extraction under reflux of the extraction solvent, it is preferable to heat and reflux for 30 minutes to several hours.
 また、50℃より低い温度で浸漬して抽出することも可能であるが、その場合には、上記の時間よりも長時間浸漬するのが好ましい。抽出操作は、同一材料について1回だけ行ってもよいが、複数回、例えば、2~5回程度繰り返すのが抽出効率の点から好ましい。 It is also possible to immerse and extract at a temperature lower than 50°C, but in that case, it is preferable to immerse for a longer time than the above time. The extraction operation may be performed only once for the same material, but it is preferable to repeat the extraction operation a plurality of times, for example, about 2 to 5 times, from the viewpoint of extraction efficiency.
 固形物を抽出後にろ過して得られる抽出液は、常法により濃縮して、これを抽出エキスとする。濃縮は、減圧下に行うのが好ましい。濃縮は抽出液が乾固するまで行ってもよい。
 抽出物は、そのまま本発明の組成物を調製するのに用いてもよいが、粉末状または凍結乾燥した乾燥エキス品等として本発明に用いてもよい。これらの固形物とする方法は、当該分野で公知の方法を採用することができる。
The extract obtained by filtering the solid matter after filtration is concentrated by a conventional method to obtain an extract. Concentration is preferably performed under reduced pressure. Concentration may be performed until the extract is dried.
The extract may be used as it is for preparing the composition of the present invention, or may be used in the present invention as a powdery or lyophilized dry extract product or the like. As a method for making these solids, a method known in the art can be adopted.
 本発明における茶花エキスは、濃縮乾固物または凍結乾燥物を包含する。
 また、本発明では、茶花抽出液を濃縮した抽出物を、溶媒による分配抽出、すなわち、水と非水和性有機溶媒とを用いる分配抽出に単回または複数回付し、有機溶媒可溶画分と水溶性画分として分離することができる。
The tea flower extract in the present invention includes a concentrated dried product or a lyophilized product.
Further, in the present invention, the extract obtained by concentrating the tea flower extract is subjected to partition extraction with a solvent, that is, partition extraction using water and a non-hydratable organic solvent, once or multiple times to obtain an organic solvent-soluble fraction. And water-soluble fraction.
 非水和性有機溶媒としては、酢酸エチル、n-ブタノール、ヘキサン、クロロホルムなどが挙げられるが、中でも酢酸エチルが好ましい。
 すなわち、茶花の水または含水低級アルコール抽出物を濃縮して得られた抽出物を、必要に応じて酢酸エチルと水を用いて分配し、酢酸エチル可溶画分と水溶性画分として得ることができる。
Examples of the non-hydratable organic solvent include ethyl acetate, n-butanol, hexane, chloroform and the like, among which ethyl acetate is preferable.
That is, the extract obtained by concentrating the water or hydrous lower alcohol extract of tea flowers is distributed with ethyl acetate and water as necessary to obtain an ethyl acetate-soluble fraction and a water-soluble fraction. You can
 また、上記で得られる水溶性画分を、さらに水と非水和性有機溶媒を用いる分配抽出に付し、有機溶媒可溶画分と水溶性画分として分離することができる。
 この場合の非水和性有機溶媒としては、n-ブタノール、ヘキサン、クロロホルムなどが挙げられるが、中でもn-ブタノールが好ましい。
 すなわち、上記の酢酸エチルと水との分配後の水溶性画分をそのままn-ブタノールとの分配に付すか、または該水溶性画分を濃縮して得られる残渣をさらに水とn-ブタノールとの分配に付し、n-ブタノール画分と水溶性画分を得ることができる。
The water-soluble fraction obtained above can be further subjected to partition extraction using water and a non-hydratable organic solvent to separate it as an organic solvent-soluble fraction and a water-soluble fraction.
Examples of the non-hydratable organic solvent in this case include n-butanol, hexane, chloroform and the like, among which n-butanol is preferable.
That is, the water-soluble fraction obtained after the partition between ethyl acetate and water is directly subjected to partition with n-butanol, or the residue obtained by concentrating the water-soluble fraction is further mixed with water and n-butanol. Then, the n-butanol fraction and the water-soluble fraction can be obtained.
 茶花エキスは、サプリメントの原料としても市販されており、この市販されている茶花エキスを本発明の目的に使用することができる。このような市販の茶花エキスとしては、「茶花乾燥エキス(株式会社日本薬用食品研究所製)」を例示することができる。本発明に使用する茶花エキスとしては、茶花エキス中に茶花サポニンを総サポニンとして1.5質量%以上含有するものが好ましい。
 茶花エキスはエキス乾燥物として、本発明の組成物に対しヒト1回あたりの摂取量が25~500mg、好ましくは50~250mg含有するように配合する。
Tea extract is also commercially available as a raw material for supplements, and this commercially available tea extract can be used for the purpose of the present invention. Examples of such commercially available tea flower extract include "tea flower dried extract (manufactured by Japan Medicinal Food Research Institute Co., Ltd.)". As the tea flower extract used in the present invention, it is preferable that the tea flower extract contains tea flower saponins in an amount of 1.5% by mass or more as a total saponin.
The tea extract is added as a dried extract so that the composition of the present invention contains 25 to 500 mg, preferably 50 to 250 mg, per person.
(桑の葉エキス)
 桑の葉は、クワ科クワ属の植物の葉であり、カイコの餌にする以外にお茶としても古くから用いられている。一般にクワと呼ばれる植物は、ヤマグワ(M.bombycis)、ナガミグワ(M.laevigata)、ケグワ(M.tiliaefolia)などが代表的である。本発明において桑の葉エキスは市販品を使用することができ、日本新薬株式会社、豊玉香料株式会社等から市販されている。
(Mulberry leaf extract)
Mulberry leaves are leaves of the mulberry genus of the mulberry family, and have been used for a long time as tea as well as for feeding silkworms. Typical examples of plants generally called mulberry are Yamaguchi (M. bombycis), Nagamiguwa (M. laevigata), and Keguwa (M. tiliaefolia). In the present invention, the mulberry leaf extract may be a commercially available product, and is commercially available from Nippon Shinyaku Co., Ltd., Toyoda Fragrance Co.
 桑の葉エキスは熱水抽出物あるいは含水エタノール抽出物が好ましい。例えば、桑の葉の生葉又は乾燥葉を細断し熱水中にて15分間以上抽出し、次いで濃縮及び乾燥処理して粉末状にしたものである。なお、本発明において桑の葉エキスは前記粉末状物だけでなく、乾燥せずに得られる濃縮液状物、濃縮せずに得られる液状抽出物等も使用できる。
 桑の葉エキスはエキス乾燥物として、本発明の組成物に対しヒト1回あたりの摂取量が50~1000mg、好ましくは100~500mg含有するように配合する。
The mulberry leaf extract is preferably a hot water extract or a hydrous ethanol extract. For example, fresh or dried leaves of mulberry leaves are shredded, extracted in hot water for 15 minutes or more, and then concentrated and dried to obtain a powder. In the present invention, the mulberry leaf extract is not limited to the above-mentioned powdery substance, and a concentrated liquid substance obtained without drying, a liquid extract obtained without concentration and the like can be used.
The mulberry leaf extract is blended as an extract dried product so that the composition of the present invention contains 50 to 1000 mg, preferably 100 to 500 mg, per person.
(キトサン)
 キトサン(Chitosan)とは、多糖類の一種で、ポリ-β1→4-グルコサミンのことである。直鎖型の多糖類でグルコサミンの1,4-重合物で、分子量は数千から数十万に及ぶ高分子物質である。
 本発明で用いられるキトサンとしては、カニ、エビの甲皮、昆虫の甲殻、イカ、キノコ及び糸状菌等の細胞壁より得られた物等が挙げられる。好ましくはカニ、エビの甲皮より得られたものがよい。キトサンは、グルコサミン、アセチルグルコサミンを成分とし、酸性の水に溶解するもので、平均分子量は通常1万以上あればよいが、好ましくは、平均分子量10万以上で、回転粘度が20mPa・s以上であり、より好ましくは、平均分子量が80万以上で、回転粘度が100mPa・s以上である。また、キトサンの粒度は特に制限はないが、好ましくは30メッシュパス以下であり、より好ましくは80メッシュパス以下の細かいものが良い。キトサンはダイエット用食品の原料として市販されており、例えば日本化薬フードテクノ社の製品を用いることができる。
 キトサンは、本発明の組成物に対し、ヒト1回あたりの摂取量が25~1000mg、好ましくは50~500mg含有するように配合する。
(Chitosan)
Chitosan is a kind of polysaccharide, poly-β1→4-glucosamine. It is a linear polysaccharide, a 1,4-polymer of glucosamine, which is a high molecular weight substance with a molecular weight of several thousand to several hundred thousand.
Examples of chitosan used in the present invention include those obtained from cell walls such as crab, shrimp carapace, insect shell, squid, mushroom and filamentous fungi. Those obtained from the crust of shrimp and shrimp are preferable. Chitosan is composed of glucosamine and acetylglucosamine and is soluble in acidic water. The average molecular weight is usually 10,000 or more, but preferably the average molecular weight is 100,000 or more and the rotational viscosity is 20 mPa·s or more. And more preferably, the average molecular weight is 800,000 or more and the rotational viscosity is 100 mPa·s or more. The particle size of chitosan is not particularly limited, but is preferably 30 mesh pass or less, more preferably 80 mesh pass or less. Chitosan is commercially available as a raw material for diet foods, and for example, a product of Nippon Kayaku Food Techno Co., Ltd. can be used.
Chitosan is added to the composition of the present invention so as to be contained in an amount of 25 to 1000 mg, preferably 50 to 500 mg per person.
 本発明の組成物にあっては、茶花エキス乾燥物1質量部当たり桑の葉エキス乾燥物2~4質量部、キトサン1~2質量部を含有するように配合する。このような配合比とすることで、効果的な食後血糖値上昇抑制作用を発揮する。
 なお、動物試験によって本発明者らが評価したところ、公知の桑の葉エキスとキトサンの組み合わせでは、従来技術で公知のレベルの食後血糖値上昇抑制作用を示す。また血糖値上昇抑制作用が知られている茶花エキスについて本願発明者らが試験したところ、動物試験においては食後血糖値上昇抑制作用を発揮しなかった。しかし茶花エキス、桑の葉エキス、キトサンの3成分を含有する組成物は、優れた食後血糖値上昇抑制作用を示した。したがって、この茶花エキス、桑の葉エキス、キトサンの3成分を配合した組成物は、従来にない強い食後血糖値上昇抑制効果を発揮する。
The composition of the present invention is blended so as to contain 2 to 4 parts by mass of dried matter of mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract. With such a blending ratio, an effective postprandial blood glucose level increase suppressing action is exhibited.
In addition, when evaluated by the present inventors by an animal test, a known combination of mulberry leaf extract and chitosan exhibits a postprandial blood glucose level elevation-inhibiting effect of a level known in the prior art. Further, when the inventors of the present invention tested a tea flower extract known to have an inhibitory effect on blood sugar level elevation, they did not exhibit an inhibitory effect on postprandial blood glucose level elevation in animal tests. However, the composition containing the three components of tea flower extract, mulberry leaf extract, and chitosan showed an excellent inhibitory effect on postprandial blood glucose level elevation. Therefore, the composition containing the three components of the tea flower extract, mulberry leaf extract, and chitosan exerts an unprecedented strong effect of suppressing the increase in postprandial blood glucose level.
 また本発明の組成物は、食品や飲料に配合しても差し支えなく、食事を摂るタイミングに合せて摂取することが好ましい。 The composition of the present invention may be added to foods and beverages, and it is preferable to take it at the timing of eating.
 本発明の組成物は、そのまま、あるいは製剤化し、健康食品やサプリメント錠に配合することもできる。
 なお製剤化に当たっては、賦形剤やその他の有効成分を本発明の組成物の目的を阻害しない範囲で使用することができる。具体的には、シクロデキストリン、へミセルロース、リグニン、グアーガム、コンニャクマンナン、イサゴール、アルギン酸、寒天、カラギーナン、キチン、カルボキシルメチルセルロース、ポリデキストロースなどの食物繊維や増粘剤、食用油、カルシウム、鉄、ナトリウム、亜鉛、銅、カリウム、リン、マグネシウム、ヨウ素、マンガン、セレンなどのミネラル;ビタミンA、ビタミンC、ビタミンD、ビタミンE、ビタミンK、ナイアシン、葉酸、パントテン酸などの脂溶性又は水溶性のビタミン群、グリセリン脂肪酸エステル、ショ糖脂肪酸エステル、ソルビタン脂肪酸エステル、プロピレングリコール脂肪酸エステル、リン脂質、アラビアガム、キサンタンガム、トラガカントガム、ローカストビーンガムなどの乳化剤や分散剤、増量剤、賦形剤、保存料・酸化防止剤、風味調整剤や香料、塩化ナトリウム、グルタミン酸ナトリウム、グリシン、コハク酸、乳酸ナトリウムなどの呈味料、クエン酸、クエン酸ナトリウム、酢酸、アジピン酸、フマル酸、リンゴ酸などの酸味料、マルチトール、アスパルテームなどの低カロリー甘味料、着色剤などである。
The composition of the present invention can be incorporated into health foods or supplement tablets as it is or after being formulated.
Upon formulation, excipients and other active ingredients can be used within a range that does not impair the purpose of the composition of the present invention. Specifically, cyclodextrin, hemicellulose, lignin, guar gum, konjac mannan, isagole, alginic acid, agar, carrageenan, chitin, carboxymethylcellulose, polydextrose and other dietary fiber and thickener, edible oil, calcium, iron, Minerals such as sodium, zinc, copper, potassium, phosphorus, magnesium, iodine, manganese, and selenium; fat-soluble or water-soluble such as vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, niacin, folic acid, and pantothenic acid Vitamin group, glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, phospholipid, gum arabic, xanthan gum, tragacanth gum, emulsifier and dispersant such as locust bean gum, extender, excipient, preservative・Antioxidants, flavor modifiers and flavors, flavoring agents such as sodium chloride, sodium glutamate, glycine, succinic acid, sodium lactate, etc., sourness such as citric acid, sodium citrate, acetic acid, adipic acid, fumaric acid, malic acid, etc. And low-calorie sweeteners such as maltitol and aspartame, and coloring agents.
 以下に本発明の組成物を用いた試験例を示し、本発明をさらに説明する。
<1.食後血糖値上昇抑制作用確認のための動物試験>
1.使用動物
 ddyマウス、試験開始時8週齢、オス、40匹を購入し、体重を測定し、群間の体重ばらつきのないように1群8匹として5群に群分けした。動物搬入後、約一週間を馴化期間とし、馴化期間の最終日夕方頃より12時間以上絶食させた。
The present invention will be further described below by showing test examples using the composition of the present invention.
<1. Animal test for confirming the postprandial blood glucose elevation suppression effect>
1. Animals to be used ddy mice, 8 weeks old at the start of the test, 40 males were purchased, and their weights were measured, and each group was divided into 5 groups, with 8 mice per group. After carrying in the animals, a acclimation period was set to about one week, and the animals were fasted for 12 hours or more from the evening of the last day of the acclimation period.
2.投与試験
 マウスに絶食下で、被験物質を蒸留水に溶解させた溶液5mL/kgで強制経口投与し、その後、糖質(ショ糖)を同様に2g/5mL/kg強制経口投与した。
2. Administration test Under fasting, the mice were forcibly orally administered with a solution of the test substance dissolved in distilled water at 5 mL/kg, and then similarly forcibly orally administered with sugar (sucrose) at 2 g/5 mL/kg.
3.被験物質
 被験物質の投与群と投与量は次のとおりである。
(1)コントロール(蒸留水5mL/kg)
(2)キトサン66.6mg/kg+桑の葉エキス(図中「クワ」と記載)133.44mg/kg
(3)茶花エキス(図中「チャカ」と記載)39.96mg/kg
(4)キトサン66.6mg/kg+桑の葉エキス133.44mg/kg+茶花エキス39.96mg/kg
(5)陽性対照(ポジコン) アカルボース10mg/kg
 なお陽性対照として用いたアカルボースは、炭水化物の消化に必要な消化酵素、特に小腸から分泌されるα-グルコシダーゼや膵臓から分泌されるα-アミラーゼを阻害する糖尿病治療用医薬品で、食後血糖値上昇を抑制することが知られている。
 なお、キトサン、桑の葉エキス及び茶花エキスの上記配合量は、下記表1のヒト等価容量(ヒト体重53kg)の3倍量相当になるように計算して設定した。
3. Test substance The administration group and dose of the test substance are as follows.
(1) Control (distilled water 5 mL/kg)
(2) Chitosan 66.6 mg/kg+mulberry leaf extract (described as “mulberry” in the figure) 133.44 mg/kg
(3) Tea flower extract (described as "Chaka" in the figure) 39.96 mg/kg
(4) Chitosan 66.6 mg/kg+mulberry leaf extract 133.44 mg/kg+tea flower extract 39.96 mg/kg
(5) Positive control (Posicon) Acarbose 10 mg/kg
Acarbose, which was used as a positive control, is a drug for the treatment of diabetes that inhibits digestive enzymes required for digesting carbohydrates, especially α-glucosidase secreted from the small intestine and α-amylase secreted from the pancreas, and increases postprandial blood glucose levels. Known to suppress.
The above-mentioned amounts of chitosan, mulberry leaf extract and tea flower extract were calculated and set so as to correspond to three times the human equivalent capacity (human body weight 53 kg) in Table 1 below.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
4.食後血糖値測定
 試験当日、上記被験物質投与前に尾静脈から約30μL採血した。
ショ糖投与後30、60、90、120、180分後に約30μLを上記と同様に採血した。採取した血液より血漿を得て、凍結保存し、後日血漿グルコース濃度を測定した。
 結果の統計処理は、平均値を及び標準偏差からTukey検定を行い、P<0.05の危険率で有意差判定を行った。
4. Postprandial blood glucose measurement On the day of the test, about 30 μL of blood was collected from the tail vein before administration of the test substance.
Approximately 30 μL of blood was collected at 30, 60, 90, 120 and 180 minutes after administration of sucrose in the same manner as above. Plasma was obtained from the collected blood, frozen and stored, and the plasma glucose concentration was measured at a later date.
As the statistical processing of the results, Tukey test was performed from the average value and the standard deviation, and a significant difference was determined at a risk rate of P<0.05.
5.試験結果
(1)血糖値の経時変化
 血糖値の経時測定結果に基づき、血糖値経時変化及び各測定時間の血糖値-被験物質投与前の血糖値=Δ経時変化を求め、それぞれプロットしで血糖変動グラフを作成した。血糖経時変化(図1)、Δ経時変化(図2)を示す。
 図1、図2に示すとおり、本発明の組成物は医薬品のアカルボースとほぼ同様に血糖の上昇を抑制した。興味深いことに茶花エキス(チャカ)は公知の先行技術情報とは異なり、血糖値上昇抑制は殆どみられなかった。これはΔ経時変化のグラフでは、より明確に確認できた。
 また、茶花エキス、桑の葉エキス、キトサンの3成分を配合することで顕著に食後血糖値上昇を抑制した。
5. Test results (1) Time course of blood glucose level Based on the results of blood glucose level measurement over time, blood glucose level time course and blood glucose level at each measurement time-blood glucose level before administration of test substance = Δ time course were obtained, and blood glucose was plotted respectively. A variation graph was created. The changes over time in blood glucose (FIG. 1) and Δ over time (FIG. 2) are shown.
As shown in FIG. 1 and FIG. 2, the composition of the present invention suppressed the rise in blood glucose almost in the same manner as the pharmaceutical product acarbose. Interestingly, unlike the known prior art information, tea flower extract (Chaka) showed almost no inhibition of blood glucose elevation. This can be confirmed more clearly in the graph of Δ change over time.
Moreover, the postprandial blood glucose elevation was remarkably suppressed by blending the three components of tea flower extract, mulberry leaf extract, and chitosan.
(2)糖の吸収
 糖の吸収量を確認するため、経時変化のグラフからAUC及びΔAUCを計算し図3、
図4に示す。AUC、ΔAUCからも明らかなように、本発明の組成物は医薬品のアカルボースとほぼ同様に糖の吸収を顕著に抑制した。
 また興味深いことに茶花エキス(チャカ)は公知の先行技術情報とは異なり、糖の吸収を抑制しなかった。しかし、図3、図4に示すとおり、茶花エキス、桑の葉エキス、キトサンの3成分を配合することで顕著に糖の吸収を抑制した。
(2) Absorption of sugar In order to confirm the absorption amount of sugar, AUC and ΔAUC were calculated from the graph of changes over time, and FIG.
As shown in FIG. As is clear from AUC and ΔAUC, the composition of the present invention remarkably suppressed the absorption of sugar almost in the same manner as the pharmaceutical product acarbose.
Interestingly, tea flower extract (Chaka) did not suppress the absorption of sugar, unlike the known prior art information. However, as shown in FIGS. 3 and 4, the incorporation of the three components of the tea flower extract, mulberry leaf extract, and chitosan significantly suppressed the absorption of sugar.
<2.ヒト臨床試験(1)>
 ヒト臨床試験により本発明組成物の食後血糖値上昇抑制効果を試験した。
・試験方法
1.被験者
(1)選択基準
  1)年齢が満20歳以上満65歳未満の日本人成人男女(年齢は同意取得日とする)
  2)空腹時血糖値が125(mg/dL)以下の者
  3)負荷食品摂取30分後又は60分後の血糖値が140(mg/dL)以上の者
  4)負荷食品摂取120分後の血糖値が199(mg/dL)以下の者
 以上の条件を満たした成人男女40名を被験者とした。
 また被験者40名は、無作為にA群とB群に群分けした(1群20名、2群)。
<2. Human clinical trial (1)>
The inhibitory effect on postprandial blood glucose level elevation of the composition of the present invention was tested in a human clinical test.
Test method 1. Subjects (1) Selection criteria 1) Japanese adult males and females aged 20 to less than 65 (age is the date of consent acquisition)
2) Persons with fasting blood glucose level of 125 (mg/dL) or less 3) Persons with blood glucose level of 140 (mg/dL) or more 30 minutes after or 60 minutes after ingestion of loaded food 4) 120 minutes after ingestion of loaded food Subjects with blood glucose level of 199 (mg/dL) or less 40 adult men and women who satisfied the above conditions were used as subjects.
40 subjects were randomly divided into A group and B group (1 group 20 persons, 2 groups).
2.試験食
(1)被験食 打錠成形した錠剤(CAL)
(1回摂取量錠剤3粒あたり) 桑の葉エキス(乾燥物)200mg
                 キトサン       100mg 
                 茶花エキス(乾燥物)  60mg  
を配合する。
 その他錠剤を製造するために次の成分を賦形剤として配合した。
 セルロース、でんぷん、ヒドロキシプロピルセルロース、二酸化ケイ素、ステアリン酸カルシウム、シェラック、貝殻未焼成カルシウム、着色料(プラセボのみ)、セルロース、でんぷん、リン酸一水素カルシウム、ステアリン酸カルシウム、シェラック
2. Test meal (1) Test meal Tablets formed by tablet compression (CAL)
(1 dose 3 tablets) Mulberry leaf extract (dry matter) 200mg
Chitosan 100mg
Tea flower extract (dry product) 60mg
Is compounded.
In addition, the following ingredients were added as excipients to produce tablets.
Cellulose, starch, hydroxypropyl cellulose, silicon dioxide, calcium stearate, shellac, uncalcined shell calcium, colorant (placebo only), cellulose, starch, calcium monohydrogen phosphate, calcium stearate, shellac.
(2)プラセボ食 打錠成形した錠剤(P)
 上記の賦形剤のみを打錠成形した。
(2) Placebo food tablet (P)
Only the above excipients were tabletted.
3.糖質負荷
 被験者は、被験食またはプラセボを摂取後糖質負荷としてレトルト米飯200g(「サトウのごはん」商品名)を摂取する。なお米飯の栄養成分は次のとおりである。
3. Carbohydrate load The subject ingests 200 g of retort cooked rice (trade name of "Sato no rice") as a sugar load after ingesting a test meal or a placebo. The nutritional components of cooked rice are as follows.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
 糖質負荷は、空腹時採血後、水150mLとともに被験食品を摂取し、10分後に「サトウのごはん」200gを水150mLとともに10分間で摂取する。米飯摂取開始後、30分、60分、120分に採血する。なお試験は、I期、II期にわけ、被験者は、試験食を被験食とプラセボの両方とも摂取するクロスオーバー試験とした(4日以上の空白期間をおく)。なお採血した血液試料は、血糖値及びインスリン値を測定した。 For carbohydrate loading, after fasting blood sampling, ingest the test food with 150 mL of water, and 10 minutes later, ingest 200 g of “rice sugar” with 150 mL of water for 10 minutes. Blood is collected at 30, 60, and 120 minutes after the start of ingestion of cooked rice. The test was divided into stage I and stage II, and the subject was a crossover test in which both the test meal and the placebo were ingested (a blank period of 4 days or more was set). The blood samples collected were measured for blood glucose level and insulin level.
・試験結果
 図5に血糖値の測定結果のグラフ、図6にインスリンの測定結果のグラフを示す。
 プラセボ(P)摂取時に比べ被験食品(CAL)摂取時のほうが、米飯負荷30分後、60分後の血糖値および120分後までのAUCが有意に低値であった。インスリンにおいても同様の結果であった。したがって本発明の組成物は、ヒトの食後血糖値上昇を抑制することが確認できた。
-Test results Fig. 5 shows a graph of blood glucose measurement results, and Fig. 6 shows a graph of insulin measurement results.
When the test food (CAL) was ingested, the blood glucose level after 30 minutes and 60 minutes after the rice load and the AUC up to 120 minutes after administration of the placebo (P) were significantly lower. Similar results were obtained with insulin. Therefore, it was confirmed that the composition of the present invention suppresses an increase in postprandial blood glucose level in humans.
<3.ヒト臨床試験(2)>
 ヒト臨床試験により本発明組成物の食後血中トリグリセリド上昇抑制効果を試験した。
・試験方法
 食後血糖値上昇抑制効果試験と同様に、脂質負荷試験を行い食後の血中トリグリセリドを測定した。なお脂質負荷食は次の組成の食品を調製した。
<3. Human clinical trial (2)>
A human clinical test was conducted to test the inhibitory effect on postprandial blood triglyceride elevation of the composition of the present invention.
-Test method Similar to the postprandial blood glucose level elevation inhibitory effect test, a lipid tolerance test was carried out to measure postprandial blood triglyceride. As the lipid-loaded food, a food having the following composition was prepared.
(1)脂質負荷食品の調整
 コーンクリームスープ(バター(よつ葉バター、食塩不使用、よつ葉乳業(株))20.0gとラード(ラード、雪印メグミルク(株)、)13.9gをコーンポタージュ(コーンクリームポタージュ、名古屋製酪(株))200.0gに溶かして混合したもの(総脂質量40.0g)を調製し、これを脂質負荷食品とした。
(1) Preparation of fat-laden foods Corn cream soup (butter (yotsuba butter, salt-free, yotsuba dairy Co., Ltd.) 20.0 g and lard (lard, Snow Brand Megmilk Co., Ltd.) 13.9 g are corn potage (corn A mixture (200.0 g of cream potage, Nagoya Dairy Co., Ltd.) dissolved and mixed (total lipid amount: 40.0 g) was prepared, and this was used as a lipid-loaded food.
・試験結果
 図7にトリグリセリドの測定結果のグラフを示す。
 プラセボ(P)摂取時に比べ被験食品(CAL)摂取時のほうが、脂質負荷2、3、4、6時間後の血中トリグリセリド値および6時間後までのAUCが有意に低値であった。
したがって本発明の組成物は、ヒトの食後血糖値上昇を抑制することが確認できた。
 なお臨床試験(1)、(2)とも被験者の健康には全く問題がなかった。
-Test result Fig. 7 shows a graph of the measurement result of triglyceride.
When the test food (CAL) was ingested, the blood triglyceride level after 2, 3, 4 and 6 hours of lipid loading and the AUC up to 6 hours after administration of the placebo (P) were significantly lower.
Therefore, it was confirmed that the composition of the present invention suppresses an increase in postprandial blood glucose level in humans.
In addition, in the clinical tests (1) and (2), there was no problem in the health of the subject.

Claims (4)

  1.  茶花エキス、桑の葉エキス、及びキトサンを有効成分として含有する食後血糖値上昇抑制用及び/または食後血中トリグリセリド上昇抑制用組成物。 A composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride, which comprises tea flower extract, mulberry leaf extract, and chitosan as active ingredients.
  2.  茶花エキス乾燥物1質量部当たり桑の葉エキス乾燥物2~4質量部、キトサン1~2質量部を含有する請求項1に記載の組成物。 The composition according to claim 1, which comprises 2 to 4 parts by mass of dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract.
  3.  食事摂取直前に飲用するための請求項1または2に記載の組成物。 The composition according to claim 1 or 2 for drinking just before eating a meal.
  4.  茶花エキス乾燥物として25~500mg、桑の葉エキス乾燥物として50~1000mg、キトサン25~1000mgを含有する食後血糖値上昇抑制用及び/または食後血中トリグリセリド上昇抑制用組成物。 A composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride, comprising 25 to 500 mg of a dried tea flower extract, 50 to 1000 mg of a dried product of mulberry leaf extract, and 25 to 1000 mg of chitosan.
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