WO2006085523A1 - Composition inhibant l’augmentation du niveau de glycemie - Google Patents

Composition inhibant l’augmentation du niveau de glycemie Download PDF

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Publication number
WO2006085523A1
WO2006085523A1 PCT/JP2006/302047 JP2006302047W WO2006085523A1 WO 2006085523 A1 WO2006085523 A1 WO 2006085523A1 JP 2006302047 W JP2006302047 W JP 2006302047W WO 2006085523 A1 WO2006085523 A1 WO 2006085523A1
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WO
WIPO (PCT)
Prior art keywords
blood glucose
thaumatin
glucose level
body weight
increase
Prior art date
Application number
PCT/JP2006/302047
Other languages
English (en)
Japanese (ja)
Inventor
Naofumi Kitabatake
Tetsuya Masuda
Hiroko Naito
Original Assignee
Kyoto University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kyoto University filed Critical Kyoto University
Priority to JP2007502605A priority Critical patent/JPWO2006085523A1/ja
Publication of WO2006085523A1 publication Critical patent/WO2006085523A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/168—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/41—Porphyrin- or corrin-ring-containing peptides
    • A61K38/415—Cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • 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
    • 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
    • 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

  • Composition for inhibiting increase in blood glucose level Composition for inhibiting increase in blood glucose level
  • the present invention relates to a composition for suppressing an increase in blood glucose level, and more specifically, a pharmaceutical comprising a basic protein such as thaumatin as an active ingredient, particularly suppressing an increase in blood glucose level after ingestion of carbohydrates. , Food-like compositions.
  • thaumatin is known as a sweet protein that is contained in the fruits of fruit trees planted in Africa, and has recently been used as a food additive for low-calorie, high-sweetness sweeteners. Have been developed (see, for example, Patent Documents 1, 2 and 3).
  • thaumatin has an effect of suppressing an increase in blood glucose level after intake of carbohydrates.
  • thaumatin has an inhibitory action on the increase in blood glucose level of basic proteins including thaumatin.
  • Patent Document 1 Japanese Unexamined Patent Publication No. 2000-197462
  • Patent Document 2 Japanese Patent Laid-Open No. 2000-270809
  • Patent Document 3 Japanese Unexamined Patent Application Publication No. 2004-129595
  • the main object of the present invention is to provide a composition for suppressing an increase in blood glucose level as a novel use of thaumatin and other basic proteins.
  • the present inventors are not aware of the mechanism of action and receptors of thaumatin as a sweet protein. Through extensive research, we have found that oral administration of thaumatin strongly suppresses the increase in blood glucose level after ingestion of dalcose in mice and humans. In addition, the inventors have
  • a composition for suppressing an increase in blood glucose comprising as an active ingredient a basic protein having an isoelectric point of about 9 or more or a degradation product thereof having an inhibitory action on an increase in blood glucose,
  • composition according to the above (1), wherein the basic protein is thaumatin
  • composition according to (1) above which is a pharmaceutical product
  • composition according to the above (1) which is a food
  • Saumatine used as an active ingredient of the yarn composition for suppressing an increase in blood glucose level of the present invention is an extremely low-toxic food additive, cytochrome C is a biological component, and lysozyme has little side effects and is orally administered.
  • V is a highly safe substance, and the composition for suppressing an increase in blood glucose level of the present invention contains a relatively small amount before, simultaneously with, or after the intake of saccharides. Oral administration can safely and significantly suppress an increase in blood glucose level.
  • the amount of a known blood sugar level increase inhibiting ingredient per ingestion is: indigestible dextrin number g, guava leaf polyphenol 0.2 g, wheat albumin 125 mg L-arabinose 180 mg, soybean drum extract 0.3 g
  • thaumatin sharply suppresses an increase in blood glucose levels at several mg.
  • FIG. 1 is a graph showing the effect of thaumatin on the change in blood glucose level over time in the mouse of Test Example 1.
  • FIG. 2 is a graph showing the effect of thaumatin on the change in blood glucose level over time in humans of Test Example 2.
  • FIG. 3 is a graph showing the effect of thaumatin administration time on the time-dependent change in blood glucose level in the mouse of Test Example 3.
  • FIG. 4 is a graph showing the effect of cytochrome C on the time course of blood glucose level in the mouse of Test Example 4.
  • FIG. 5 is a graph showing the effect of lysozyme on the time course of blood glucose level in the mouse of Test Example 5.
  • FIG. 6 is a graph showing the effect of thaumatin on the time course of blood glucose level in the human of Test Example 6.
  • FIG. 7 is a graph showing the effects of lysozyme, monelin, ribonuclease, thaumatin, and cytochrome C on the time course of blood glucose level in the mouse of Test Example 7.
  • FIG. 8 is a graph showing the dose-dependent effect of thaumatin on the change in blood glucose level over time in the mouse of Test Example 8.
  • FIG. 9 is a graph showing the glucose absorption inhibitory effect of thaumatin in Test Example 9 in human small intestine model cells.
  • FIG. 10 is a graph showing the persistence of cytochrome C blood glucose level increase inhibitory effect in the mouse of Test Example 10.
  • Examples of the basic protein having an isoelectric point of about 9 or more used as an active ingredient of the composition for suppressing an increase in blood glucose level of the present invention include thaumatin (isoelectric point 11.7), cytochrome C (isoelectric point). Point 10), lysozyme (isoelectric point 11), ribonuclease (isoelectric point 9.5), monelin (isoelectric point 11), etc., and thaumatin is preferred. These can be used as commercially available products.
  • the compounding amount of the active ingredient in the composition for suppressing an increase in blood glucose level of the present invention is not particularly limited and can be appropriately selected depending on the dosage form of the composition, etc., but is generally 0.005 to 95 with respect to the total amount of the composition. It is about 0.1% by weight, preferably about 0.01 to 80% by weight, and is not particularly limited. Usually, for adults (with a body weight of 60kg), 0.1 to 1 time: L00mg, preferably 1 to: An amount capable of administering or ingesting an active ingredient of about LOmg.
  • the composition for suppressing an increase in blood glucose level of the present invention is a liquid, semi-solid or solid pharmaceutical product and food and drink suitable for oral administration or ingestion directly or by dilution or division, etc., according to a conventional method. It can be made the form.
  • the liquid dosage form include a solution, a syrup, an emulsion, a suspension, and the like.
  • Examples of the semi-solid dosage form include a paste.
  • Examples of the solid dosage form include, for example, Examples include pharmaceutical forms such as powders, granules, tablets, and capsules, and various food forms.
  • the composition for suppressing an increase in blood glucose level of the present invention is within a range not violating its purpose.
  • a carrier an excipient, a diluent, a binder, a disintegrant, a surfactant, a lubricant, a colorant.
  • it may contain known additives such as antioxidants, preservatives, seasonings, and fragrances.
  • composition for suppressing an increase in blood glucose level of the present invention obtained by force can be used as a pharmaceutical or a food such as a food for specified health use, and for example, as a pharmaceutical together with other pharmaceutically active ingredients.
  • various foods and drinks that are used as a food additive for suppressing blood sugar level elevation together with other edible materials can be used. Such pharmaceuticals and foods and drinks are also within the scope of the present invention.
  • composition for suppressing an increase in blood glucose level according to the present invention is, for example, as described above in the same manner as usual pharmaceuticals and foods and drinks, including the case of about 30 minutes before the meal and about 30 minutes after the meal.
  • Oral administration or ingestion to humans who need to suppress the increase in blood glucose level in the dosage range can safely and sharply suppress the increase in blood glucose level due to meals.
  • the value increase effect is persistent. If necessary, the dose can be adjusted in terms of body weight and used to suppress the increase in blood glucose level of other mammals (eg, monkeys, dogs, cats, etc.).
  • the area under the blood concentration curve up to 90 minutes after administration was also calculated.
  • the results are shown in Fig. 7.
  • the vertical axis represents the ratio (%) to the area under the blood concentration curve in the glucose administration group.
  • ⁇ / z gZg body weight (thomatin 9. administration group), purified water 120 1 Glucose 3.3 mgZg body weight and thaumatin 18 gZg body weight (Thomatin 18 g administration group) were orally administered, and blood glucose level was measured over time. The results are shown in Fig. 8. In FIG. 8, the vertical axis represents blood glucose level (mgZdl) and the horizontal axis represents elapsed time (minutes).
  • Caco-2 cell monolayer culture system a human small intestine model.
  • Caco-2 cells a human colon adenocarcinoma-derived intestinal epithelial cell line, were cultured on a permeable membrane to form a cell monolayer and used for experiments.
  • Caco-2 cell monolayers were prepared using glucose-free HEPES buffered salt soluti.
  • Thomatin 5 74 mg and an appropriate amount of flavor are dissolved in 250 ml of purified water, and sterilized and filtered to produce a liquid composition for suppressing blood glucose elevation directly for drinking.
  • Cytochrome ClOmg and an appropriate amount of flavor are dissolved in 150 ml of purified water, and sterilized to produce a liquid composition for suppressing blood sugar level elevation that is directly used for drinking.
  • Lysozyme 10mg and appropriate amount of perfume are dissolved in 150ml of purified water, and sterile filtered directly. A liquid composition for suppressing blood sugar level elevation for use in drinking is produced.
  • Ribonuclease lOmg and an appropriate amount of fragrance are dissolved in 150 ml of purified water, and sterilized by filtration to produce a liquid composition for suppressing blood sugar level elevation that is directly used for drinking.
  • Monellin lOmg and an appropriate amount of perfume are dissolved in 150 ml of purified water, and sterilized to produce a liquid composition for suppressing an increase in blood glucose level that is directly used for drinking.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Endocrinology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Botany (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne une composition permettant d'inhiber une augmentation du niveau de glycémie caractérisée en ce qu’elle contient, en tant que principe actif, une substance choisie parmi des protéines basiques telles que la thaumatine, le cytochrome C, le lysozyme, la ribonucléase et la monéline et la décomposition de leurs produits, en particulier de la thaumatine.
PCT/JP2006/302047 2005-02-09 2006-02-07 Composition inhibant l’augmentation du niveau de glycemie WO2006085523A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2007502605A JPWO2006085523A1 (ja) 2005-02-09 2006-02-07 血糖値上昇抑制用組成物

Applications Claiming Priority (2)

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JP2005-033225 2005-02-09
JP2005033225 2005-02-09

Publications (1)

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WO2006085523A1 true WO2006085523A1 (fr) 2006-08-17

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PCT/JP2006/302047 WO2006085523A1 (fr) 2005-02-09 2006-02-07 Composition inhibant l’augmentation du niveau de glycemie

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WO (1) WO2006085523A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012012360A (ja) * 2010-07-02 2012-01-19 Morinaga Milk Ind Co Ltd ハロペリドール適応症治療薬および飲食品
WO2022012926A1 (fr) * 2020-07-16 2022-01-20 Nomad Bioscience Gmbh Produits pour consommation orale à teneur réduite en sucre

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5210460A (en) * 1975-07-04 1977-01-26 Tate & Lyle Ltd Sweetening composition containing protein sweetener
JP2000270809A (ja) * 1999-03-29 2000-10-03 Yaizu Suisankagaku Industry Co Ltd 健康食品
JP2002330742A (ja) * 2001-03-08 2002-11-19 Eisai Co Ltd 食品添加組成物
JP2003284528A (ja) * 2002-03-28 2003-10-07 Nippon Paper Industries Co Ltd 畜肉食品の肉色改善剤および畜肉食品

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5210460A (en) * 1975-07-04 1977-01-26 Tate & Lyle Ltd Sweetening composition containing protein sweetener
JP2000270809A (ja) * 1999-03-29 2000-10-03 Yaizu Suisankagaku Industry Co Ltd 健康食品
JP2002330742A (ja) * 2001-03-08 2002-11-19 Eisai Co Ltd 食品添加組成物
JP2003284528A (ja) * 2002-03-28 2003-10-07 Nippon Paper Industries Co Ltd 畜肉食品の肉色改善剤および畜肉食品

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GABOR G. AND KALDOR A.: "Wirkung von Cytochrom C auf die Adrenalin-Hyperglykamie", AERZTLICHE FORSCHUNG, vol. 15, no. 8, 1961, pages II/97, XP002999674 *
TANESE T. ET AL.: "Effects of Lysozyme on Carbohydrate Metabolism in Rats", FOLIA ENDOCRINOL. JAP., vol. 52, no. 5, 1976, pages 566 - 574, XP002995962 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012012360A (ja) * 2010-07-02 2012-01-19 Morinaga Milk Ind Co Ltd ハロペリドール適応症治療薬および飲食品
WO2022012926A1 (fr) * 2020-07-16 2022-01-20 Nomad Bioscience Gmbh Produits pour consommation orale à teneur réduite en sucre

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JPWO2006085523A1 (ja) 2008-08-07

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