WO2002049661A1 - Prophylactiques/medicaments contre le diabete et aliments fonctionnels contenant ces prophylactiques/medicaments - Google Patents

Prophylactiques/medicaments contre le diabete et aliments fonctionnels contenant ces prophylactiques/medicaments Download PDF

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Publication number
WO2002049661A1
WO2002049661A1 PCT/JP2001/011090 JP0111090W WO0249661A1 WO 2002049661 A1 WO2002049661 A1 WO 2002049661A1 JP 0111090 W JP0111090 W JP 0111090W WO 0249661 A1 WO0249661 A1 WO 0249661A1
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WIPO (PCT)
Prior art keywords
diabetes
medium
preventive
cultivation
ameliorating
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PCT/JP2001/011090
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English (en)
Japanese (ja)
Inventor
Kuniaki Obara
Original Assignee
Kirin Beer Kabushiki Kaisha
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Publication of WO2002049661A1 publication Critical patent/WO2002049661A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • 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
    • A23L31/00—Edible extracts or preparations of fungi; Preparation or treatment thereof
    • 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
    • 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
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates

Definitions

  • the present invention relates to a diabetes preventive and ameliorating agent and a functional food having a diabetes preventive and ameliorating effect, and more particularly to a functional food obtained from a fruit body of a mushroom belonging to the family Climacodontaceae, such as Bunakaritake (Mycoleptodonoides aitchisonii).
  • the present invention relates to a diabetes preventive or ameliorating agent having an effect of suppressing an increase in blood glucose level and an effect of improving glucose tolerance against type 1 and type 2 diabetes, and a functional food having a diabetes preventing or ameliorating effect including such a diabetes preventing or ameliorating agent.
  • beech agaric grows on fallen beech trees and dead trees in late autumn, and umbrellas are 3 to 10 cm in diameter, semicircular white, and later. Tint yellow, back white Needle-like, later yellowish on the surface as well as the surface, the meat is white, soft and water-absorbing, and is known to have a unique aroma.As a mushroom prized as mountain meat by mountain villagers Is also known.
  • Nagano Prefectural Forest Research Report No. 3 pages 32 to 37 (1989) and Fukushima Prefectural Forest Research Report No.
  • a functional food having
  • the present inventors have previously conducted an inoculation step of inoculating a seed medium of B. agaricus inoculated on a medium supplemented with a specific nutrient source, and culturing the medium inoculated with a seed of B. agaricus, and forming a fungal bed in which the mycelia grew on the medium.
  • the present inventors have been conducting various studies on the pharmacological action of the fruit body of B. aeruginosa, which has been available stably for the whole year, and found that the body of B. aeruginosa has a blood sugar level-inhibiting action and a glucose tolerance improving action. The inventors have found that the components shown are present, and have completed the present invention. Disclosure of the invention
  • FIG. 1 is a diagram for explaining a method of cultivating a fungus bed of Bunahari yuga, which forms fruiting bodies using a translucent cultivation container.
  • the fungal bed cultivation refers to a method of inoculating a seed material into a material composed of a water retaining body and a nutrient source without using a log, and cultivating in a controlled environment of temperature, humidity, illuminance, and the like.
  • a water retaining body a culture source for cultivation containing a nutrient source including at least one of dried okara and beer lees, and a sterilization step of sterilizing a medium mixed with water
  • An inoculation step in which a sterilized medium is inoculated with a fungus inoculated with a fungus, a preculture step in which the medium inoculated with a fungus inoculated with a fungus is obtained, and a culture bed in which hypha grows in the medium is obtained.
  • a medium cultivation step for obtaining a P is
  • agaricus primordium that is not exposed to a physical space capable of growing the fruiting body; and a cultivation primordial primrose that is not exposed to the physical space capable of growing the fruiting body.
  • An artificial cultivation comprising a post-culturing step of cultivating a primordium that is exposed to a physical space in which the fungus can grow into a fruiting body and obtaining a fruiting body of the fungus can be specifically exemplified.
  • the physical space that can grow into a fruiting body refers to a space in which the fruiting body grows outward from the culture medium.
  • the culture medium is sealed with a plastic bag or the like, the physical space outside the sealed container can be obtained. Means space.
  • Fruiting bodies are clusters, umbrellas are fan-shaped to spatula-shaped, 3-8 X 3-10 cm.
  • the surface is hairless and smooth, white to slightly yellowish.
  • the meat is white, 2-5 mm thick. ⁇ is thin and slightly tooth-like.
  • the hypha consists of two hyphae, a thick hypha with a width of 4 to 10 m and a thin hypha with a swelling and twist with a width of 3.5 to 5 m.
  • Spores are intestinal, colorless, 2-2.5 x 5-6.5 m.
  • the water-retaining bodies used in the culture medium include coniferous oakakus derived from conifers such as cedar, hinoki and pine, and oakakus derived from broadleaf trees such as beech, oak and kunugi.
  • coniferous oakakus derived from conifers such as cedar, hinoki and pine
  • oakakus derived from broadleaf trees such as beech, oak and kunugi.
  • corn cob used as a product corn crushed product
  • commercially available bacterial bed materials and the like can be exemplified. These materials may be used alone or as a mixture of two or more. It can also be used.
  • the mixing ratio of the water retaining body and the nutrient for cultivation is preferably in the range of 10: 0.7 to 10: 4, and more preferably in the range of 10: 2 to 3, in terms of fresh weight ratio. Further, the water content may be adjusted to 60 to 70% per final medium, but is more preferably about 65%. Further, as a medium component, soybean hulls, dried yeast, a pH adjuster, and the like, which are usually used for mushroom cultivation, can be added as a medium component.
  • the fungal bed cultivation of B. agarita consists of a pre-culture step, a middle culture step, and a post-culture step, in which the mycelia of B. agaricus grows sufficiently in the medium under specific culture conditions, and the fruiting body is formed.
  • a pre-culture step of obtaining a bacterial bed for formation a medium culture step of culturing the bacterial bed under a specific culture condition to form a B. agaricus primordium, and culturing the formed B. agaricus primordium under a specific culture condition
  • three culturing steps of a post-culturing step of growing to fruiting bodies are employed, and thereby it is possible to obtain fruiting bodies of B. agaricus having a stable content component and the like.
  • the medium culturing step is, as described above, a step performed to form a beech bamboo shoot primordium on the bacterial bed after the completion of the pre-culturing step, and the bacterial bed obtained in the pre-culturing step is heated to a temperature of 8 to 2 hours. 2 ° C, preferably 12 to 16 ° (Humidity 80 to: L 00%, preferably 85 to 95%, illuminance 50 lux or more, preferably 50 to 500 lux When cultivation is continued for 5 to 60 days, for example, Buna hachitake primordium which is not exposed to a physical space capable of growing fruit bodies, such as between the bacterial bed and the inner surface of the container, is formed.
  • the cultivation container 1 having a rectangular cross section or the like is turned sideways so that the Bunakaritake primordium 2a is at the top, and the peripheral portion 5 of the cultivation container in which the It is preferable to harvest the large fruit body 4 of uniform shape by cultivating the fungus body 2a under conditions that expose the physical space where the fungus can grow into fruiting bodies.
  • the agent for preventing and / or improving diabetes mellitus of the present invention includes a fruit body of a mushroom belonging to the family Azotaceae or a processed product thereof, preferably a fruit body of a mushroom belonging to the genus Funeraria or a treated product thereof, and more preferably a fruit body of a fungus or a treated product thereof.
  • Any functional food may be used as long as it is an active ingredient.
  • the functional food of the present invention is not particularly limited as long as it contains such a diabetes preventive / ameliorating agent and has a diabetes preventive / ameliorating action. Not done.
  • the processed substance of the above-mentioned fruiting bodies is not particularly limited.
  • ground fruiting bodies, room-temperature water, hot water, hexane, getyl ether, acetone, black mouth form, methanol, ethanol Extracts of fruiting bodies using, etc. various enzyme-treated products of fruiting bodies, dried fruiting bodies by air drying, hot air drying, heat drying, freeze drying, microwave drying, etc., or dried powder crushed after drying Granules, capsules or tablets of the body or the dried powder by a conventional method Drying of the fruiting body in terms of suppressing the increase in blood glucose level in the fruiting body and improving the yield of components having an effect of improving glucose tolerance, preventing inactivation, and the use form as a food material, etc.
  • the drying method for preparing the dry powder is not particularly limited, but a drying method using a hot air dryer is economically superior, and the drying temperature in such a hot air drying method is 40%. It is preferable to heat at 90 ° C to 90 ° C, especially 60 ° C to 70 ° C for several hours.Drying in this temperature range produces a burning odor and blood glucose level due to the action of enzymes contained in fresh mushrooms. Inhibition of increase ⁇ A decrease in glucose tolerance improving activity can be suppressed. If the harvested fruiting body is not processed immediately, it is preferable to store it at a low temperature of 10 ° C or less, for example, at 4 to 5 ° C.
  • the diabetes preventive and ameliorating agent of the present invention can reduce fasting blood glucose and suppress a rapid increase in blood glucose immediately after ingestion, thereby preventing and improving diabetes such as suppression of blood sugar elevation and suppression of glucose tolerance. Since it has an action, it is advantageously used as a preventive or symptom-improving agent for diabetes, and as a pharmacological composition material for adding the compound to food to make it a functional food having a preventive / improving action for diabetes. be able to.
  • the diabetes preventive ameliorating agent of the present invention usually has a diabetes preventive and ameliorating effect by taking 100 mg to 20 g / kg body weight in terms of dry fruit body per day. The intake can be adjusted appropriately according to the age, etc. When used as a preventive and / or symptom-ameliorating agent for diabetes, for example, it can be mixed with excipients generally used in pharmaceutical applications and used as an orally administered drug.
  • the functional food having the diabetes preventive and ameliorating action of the present invention characterized by containing the diabetes preventive and ameliorating agent of the present invention, uses such a diabetes preventive and ameliorating agent as a part of a raw material for food and drink, Or the manufacturing process or after manufacturing It can be obtained by adding and blending in.
  • Such functional foods are not particularly limited, and include baked goods such as cookies, breads, cakes, rice crackers, etc., tablet confections such as ramune confectionery, Japanese sweets such as yokan, pudding, jelly, ice cream, etc.
  • tablet confections by pulverizing the dried fruit body of the fungus body, and tableting the fine powder according to a conventional method. It can. It is also possible to pulverize the dried fruit body of the fungus body, and mix it with lactose, dextrin, dried yeast and the like.
  • diabetes mellitus model rat Using a model rat of streptozotocin (STZ), a type 1 diabetes mellitus model animal, diabetes mellitus model rat, the preventive effect of the fruit body of B. aeruginosa on diabetes mellitus was examined as follows. Approximately 4 weeks old male SD rats were intraperitoneally administered 65 mg / kg streptozotocin to induce diabetes. One week later, rats that showed hyperglycemia, urinary glucose, heavy eating, and heavy drinking were subjected to the following experiment.
  • STZ model rat of streptozotocin
  • the STZ-diabetic model rats thus prepared were grouped into 8 rats, and a basic diet group to which CRF-1 (Charles River Japan) was administered as a basic diet, and a beech eight described in Example 2 described above so that the basic diet was 5%. They were grouped into a mixed food group of beech agaric mushrooms mixed with the dried powder of mushroom body. They were reared for 4 weeks in an environment in which food and water were freely available at a room temperature of 23 ° C and a 12-hour light / dark cycle. ⁇ Every 1 week from the start of rearing, they were fed from the rat tail vein after a 20-hour fast. Blood was collected and blood glucose was measured. In addition, a glucose tolerance test was performed at weeks 0, 2, and 4. I got it.
  • KKA y diabetes model mice which are a type 2 diabetes model animal
  • the KKA y mouse is a type 2 diabetes model mouse in which the obesity gene A y is introduced into the KK mouse exhibiting hyperglycemia and the obesity and hyperglycemia is expressed. Widely used.
  • KKA y ZT a Jc 1 mice were purchased from Clea Japan, and after one week of preliminary breeding, they were divided into 8 animals per group as in the type 1 diabetes test. The test was started in groups of mixed diets.
  • mice were housed individually in cages at room temperature of 23 ° (:, 12 hours light / dark cycle, with free access to food and water for 5 weeks.
  • Blood was collected from the fundus of the mouse using a capillary blood collection tube, blood glucose was measured, and a glucose tolerance test was performed 5 weeks after the breeding was started, ie, after fasting for 20 hours, 2 g / kg of glucose Blood was collected from the fundus before glucose administration (0 hour), 0.5 hours, 1 hour, 1.5 hours, and 2 hours after glucose administration, and blood glucose levels were measured.
  • the changes in the values are shown in Table 3.
  • the blood glucose level was significantly lower in the Bunahari Yuga mixed diet group, and the increase in the blood glucose level was suppressed.
  • Table 4 Compared to the basic diet group, Bunach In the bamboo mixed diet group, it was confirmed that the increase in blood glucose level immediately after glucose administration was significantly suppressed, and that the blood glucose level was recovered quickly. It was shown.
  • L6 cells used for the test were purchased from Dainippon Pharmaceutical Co., Ltd. L 6 cells were cultured at 3 7 ° C, 5% C_ ⁇ 2 concentration under using carbon dioxide gas incubator at basal medium (D-MEM medium containing 1 0% FBS). Cells in the growth phase were prepared and suspended in a basal medium at 4 ⁇ 10 4 cells / ml. This was added to a 24-multiwell cell culture plate (30464, manufactured by Falcon) in an amount of 1 ml each, and the cells were cultured until they became conferred.
  • the preparation of the Beechari Yuga extract was performed as follows. 0.25 of the dried powder of Beech agaricus described in Example 2 above was mixed with hexane, gethyruether, acetone, 10 ml of form, methanol, ethanol, and water respectively. Add 1 and shake overnight. For hot water extraction, 10 ml of water was added to 0.25 g of the dried powder of Bunakaritake, and the mixture was heated at 105 ° C for 5 minutes using an autoclave. These extracts were filtered with filter paper, and the filtrate was dried under reduced pressure to obtain an extract. Table 5 shows the yields. Hexane, getyl ether, acetone, chloroform, methanol, and ethanol extracts are dimethyl sulfoxide (DI MSO), and water and hot water extracts are water. And dissolved to obtain an extract.
  • DI MSO dimethyl sulfoxide
  • 3T3L1 cells used in the test were purchased from Dainippon Pharmaceutical Co., Ltd.
  • the 3T3L1 cells were cultured in a basal medium (D-MEM medium containing 10% FBS) under a 37,5% C% 2 concentration using a gas carbonate incubator.
  • Cells in the growth phase were prepared and suspended in a basal medium to 5 ⁇ 10 4 Zm 1. This was added to a 24 multi-well cell culture plate every 1 ml, and cultured until it became a confident.
  • the fungus mushroom extract 1 I 1 prepared in Example 5 was added to each medium and cultured.
  • the culture medium was taken out 48 hours after the addition of the extract, and the amount of glucose in the medium was measured.
  • Table 7 shows the amount of Darcos remaining in the medium. As can be seen from Table 7, the amount of glucose was significantly lower in the hexane, getyl ether, acetone, chloroform, and methanol extracts compared to the case without the addition of the Buna mushroom extract in the medium. Was observed. Therefore, it was shown that B. agarita may increase glucose uptake in adipose tissue and decrease blood glucose level.
  • the functional food having the diabetes preventive and ameliorating agent and the diabetes preventive and ameliorating effect of the present invention is derived from a natural product, mushroom, and is highly safe, and has a blood sugar level suppressing effect on type 1 diabetes and type 2 diabetes. Since it has a glucose tolerance improving effect, ingestion of the antitumor agent of the present invention or a functional food having a tumor improving effect can be expected to have a preventive effect on diabetes and a therapeutic effect on diabetes. In addition, by using an artificially cultivated product of Buna hachitake as a fruiting body, it is possible to manufacture an inexpensive and stable agent for preventing and ameliorating diabetes mellitus with stable quality throughout the year.

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Abstract

L'invention concerne des prophylactiques/médicaments contre le diabète provenant d'un champignon d'origine naturelle qui présentent un haut degré de sécurité, un faible coût et une bonne stabilité et qui possèdent des effets inhibant une augmentation de la glycémie et améliorant la tolérance au glucose dans les diabètes de type 1 et de type 2 ; l'invention concerne également des aliments fonctionnels contenant ces prophylactiques/médicaments contre le diabète qui possèdent des effets de prévention et d'amélioration du diabète. Pour préparer ces prophylactiques/médicaments contre le diabète possédant des effets inhibant une augmentation de la glycémie et améliorant la tolérance au glucose, on utilise comme ingrédient actif du carpophore traité d'un champignon de la famille Auriscalipiaceae, par exemple du carpophore de Mycoleptodonoides aitchisonii cultivés dans un lit pour champignons. On peut ensuite préparer des aliments fonctionnels présentant un effet antitumoral en ajoutant ces prophylactiques/médicaments contre le diabète à divers aliments. On peut vérifier l'effet d'inhibition d'une augmentation de la glycémie en mesurant la glycémie après 16 à 20 heures de jeûne et l'effet d'amélioration de la tolérance au glucose en effectuant un test de charge en glucose.
PCT/JP2001/011090 2000-12-19 2001-12-18 Prophylactiques/medicaments contre le diabete et aliments fonctionnels contenant ces prophylactiques/medicaments WO2002049661A1 (fr)

Applications Claiming Priority (2)

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JP2000386092A JP2002187851A (ja) 2000-12-19 2000-12-19 糖尿病予防・改善剤及びそれを含む機能性食品
JP2000-386092 2000-12-19

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JP4602674B2 (ja) * 2004-01-30 2010-12-22 野田食菌工業株式会社 マルターゼ阻害剤
KR100809375B1 (ko) * 2006-04-03 2008-03-05 조선대학교산학협력단 참바늘버섯과 알로에를 포함하는 건강기능식품
JP2008178363A (ja) * 2007-01-25 2008-08-07 Tohoku Univ レプチンシグナル伝達障害モデル動物
KR101267886B1 (ko) * 2010-06-30 2013-05-27 전라남도 참바늘버섯을 이용한 당뇨성 이상지질혈증 예방 및 치료용 조성물
JP2013059332A (ja) * 2012-10-26 2013-04-04 Tohoku Univ マウスの生育過程において社会的隔離に対する肥満又は糖尿病発症の感受性を解析する方法

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JPH09124541A (ja) * 1995-10-27 1997-05-13 Kagome Co Ltd 新規化合物及びこれを有効成分とする神経成長因子産生誘導剤

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JPH09124541A (ja) * 1995-10-27 1997-05-13 Kagome Co Ltd 新規化合物及びこれを有効成分とする神経成長因子産生誘導剤

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HIROSHI YOSHIDA ET AL.: "The chemical component in the vegetative mycelia of basidiomycotina", NIPPON KINGAKUKAI KAIHO, vol. 37, no. 2, 1996, pages 51 - 56, XP002909374 *
KEN YASUKAWA ET AL.: "Inhibitory effect of methanol extracts from edible mushroom on TPA-induced ear oedema and tumor promotion in mouse skin", PHOTOTHERAPY RESEARCH, vol. 10, no. 4, 1996, pages 367 - 369, XP002909376 *
YOSHIMASA KASAHARA ET AL.: "Effect of methanol extract fruit body of mycoleptodonoides aitchisonii on acute and chronic inflammation models", J. FOOD HYGIENIC SOCIETY OF JAPAN, vol. 40, no. 5, 1999, pages 368 - 374, XP002909375 *

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