WO2018159714A1 - Agent améliorant le métabolisme des sucres et/ou des lipides - Google Patents

Agent améliorant le métabolisme des sucres et/ou des lipides Download PDF

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WO2018159714A1
WO2018159714A1 PCT/JP2018/007625 JP2018007625W WO2018159714A1 WO 2018159714 A1 WO2018159714 A1 WO 2018159714A1 JP 2018007625 W JP2018007625 W JP 2018007625W WO 2018159714 A1 WO2018159714 A1 WO 2018159714A1
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paramylon
group
fiberized
sugar
test
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PCT/JP2018/007625
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English (en)
Japanese (ja)
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昭 赤司
潤 竹▲崎▼
圭 寺澤
亨祐 大木
信輝 大中
誠一郎 青江
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株式会社神鋼環境ソリューション
学校法人 大妻学院
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Priority to JP2018515680A priority Critical patent/JP7024975B2/ja
Publication of WO2018159714A1 publication Critical patent/WO2018159714A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • 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
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof

Definitions

  • the present invention relates to a sugar and / or lipid metabolism-improving agent.
  • lifestyle-related diseases have increased. This is thought to be due to changes in eating habits and lack of exercise. Lifestyle-related diseases are known to be associated with, for example, abnormal lipid metabolism and abnormal sugar metabolism. For this reason, lifestyle-related diseases can lead to various diseases such as arteriosclerosis and hypertension. Therefore, effective means for improving lipid metabolism and sugar metabolism are required to prevent such lifestyle-related diseases.
  • lipid metabolism and sugar metabolism are currently known as antidiabetic drugs and obesity-improving drugs.
  • many of these are synthetic low-molecular compounds, and natural components are desirable from the viewpoint that they can be ingested constantly. Further, from the viewpoint of more effectively preventing lifestyle-related diseases, it is desirable that both lipid metabolism and sugar metabolism can be improved.
  • Paramylon is a kind of ⁇ -1,3-glucan contained in Euglena. In recent years, it has been reported that paramylon is useful for wound treatment and allergy suppression (Patent Documents 1 and 2).
  • An object of the present invention is to provide a sugar and / or lipid metabolism-improving agent.
  • an object of the present invention is to provide a sugar and / or lipid metabolism improving agent containing a natural ingredient as an active ingredient.
  • the present inventor has found that the action of improving the metabolism of sugar and / or lipid is remarkably enhanced by fiberizing the natural ingredient paramylon. As a result of further research based on this knowledge, the present inventor completed the present invention.
  • the present invention includes the following embodiments: Item 1. A sugar and / or lipid metabolism-improving agent comprising fibrotic paramylon.
  • Item 2 The metabolism improving agent according to Item 1, which is in a dry form.
  • Item 3 The metabolism improving agent according to Item 1 or 2, wherein the fiberized paramylon is a defibrated material of paramylon particles.
  • Item 4. The metabolism improving agent according to any one of Items 1 to 3, wherein the fiberized paramylon is a network structure in which fibers are entangled.
  • Item 5 The metabolism improving agent according to any one of Items 1 to 4, which is a food additive.
  • Item 6. The metabolism improving agent according to any one of Items 1 to 4, which is a food composition.
  • Item 7. The metabolism improving agent according to any one of Items 1 to 4, which is a pharmaceutical agent.
  • Item 8 The metabolism according to any one of Items 1 to 7, which is used for prevention or amelioration of at least one selected from the group consisting of (1) metabolic syndrome, or (2) obesity, diabetes, dyslipidemia, and fatty liver. Improver.
  • Item 9 A method for producing a sugar and / or lipid metabolism-improving agent, comprising blending fiberized paramylon.
  • Item 10 The method according to Item 9, wherein the fiberized paramylon is in a dry form.
  • Item 11 The method according to Item 9 or 10, further comprising blending water.
  • Fibrotic paramylon for use as a sugar and / or lipid metabolism-improving agent.
  • Item 13 A method for improving sugar and / or lipid metabolism, including applying fibrotic paramylon to a subject.
  • Item 14 Use of fiberized paramylon to produce sugar and / or lipid metabolism improvers.
  • a sugar and / or lipid metabolism improving agent containing a natural component as an active ingredient can be provided.
  • the sugar and / or lipid metabolism improving agent of the present invention at least selected from the group consisting of metabolic syndrome, dyslipidemia such as hypercholesterolemia and hyperlipidemia, fatty liver, diabetes and obesity It is possible to prevent or ameliorate one kind of disease or condition.
  • the sugar and / or lipid metabolism-improving agent of the present invention contains a naturally-occurring polysaccharide as an active ingredient, it is considered that the risk of side effects is low. For this reason, it is suitable for long-term intake.
  • the microphotograph (upper stage) and vial appearance photograph (lower stage) of a paramylon particle suspension (PM granule) and a fiberized paramylon liquid (fiberized PM) are shown.
  • An electron micrograph of fiberized paramylon (Production Example 1) is shown.
  • the length of one scale on the lower right scale in the figure is 1 ⁇ m.
  • the enlarged view in the square frame of the photograph of FIG. 2 is shown.
  • the length of one graduation shown in the lower right of the figure is 100 nm.
  • the horizontal axis indicates the number of days elapsed from the start of the test, and the vertical axis indicates the average value of body weight. It is a graph which shows the weight gain in a test.
  • the horizontal axis shows the elapsed time from administration of the glucose solution, and the vertical axis shows the blood glucose level. * Indicates that there is a significant difference compared to the control group (p ⁇ 0.05).
  • p is 0.058. It is a graph which shows the measurement result of the retroabdominal wall fat tissue weight after a test. It is a graph which shows the measurement result of the testicular periphery fat tissue weight after a test.
  • NEFA serum free fatty acid
  • the sugar and / or lipid metabolism-improving agent containing fibrotic paramylon (herein referred to as “the metabolism-improving agent of the present invention” or “the agent of the present invention”). Yes.) This will be described below.
  • amorphous paramylon obtained by chemical treatment (alkali treatment, etc.) of paramylon particles has been reported, but this is not recognized as fiberized when observed with an electron microscope, and has a shape and size. Since it is an irregular mass, it is not included in the fiberized paramylon.
  • Euglena the fiberizing paramylon is derived is not particularly limited, for example, Euglena gracilis (Euglena gracilis), Euglena longa, Euglena caudata, Euglena oxyuris, Euglena tripteris, Euglena proxima, Euglena viridis, Euglena sociabilis, Euglena ehrenbergii, Euglena deses Euglena pisciformis , Euglena spirogyra , Euglena acus , Euglena geniculata , Euglena intermedia , Euglena mutabilis , Euglena sanguinea , Euglena stellata , Euglena terricola , Euglena klebsi , Euglena cyclopica , Euglena rubra ola, etc.
  • Euglena gracilis Eugle
  • Euglena Gracilis is preferably mentioned from the viewpoint that the effects of the present invention can be more reliably exhibited, more preferably Euglena Gracilis EOD-1 strain [product evaluation as of June 28, 2013 As the accession number FERM BP-11530 under the provisions of the Budapest Treaty at the National Institute for Biotechnology Patent Biology Center ⁇ NITE-IPOD (zip code 292-0818, room 2-5-8 Kazusa-Kamashita, Kisarazu, Chiba, Japan) ⁇ International deposits].
  • the weight average molecular weight of the fiberized paramylon is not particularly limited, but is, for example, 1 ⁇ 10 4 to 2 ⁇ 10 7 , preferably 1 ⁇ 10 5 to 5 ⁇ 10 5 .
  • the weight average molecular weight can be measured by SEC-MALS analysis by the following method: SEC apparatus: LC-10ADvp system (Shimadzu Co., Japan), column used: KD-806M (shodex., Japan) , MALS detector: DAWN HELEOSII (wyatt Technologies., USA), eluent: 1% LiCl / DMI, Flow rate: 0.5 mL / min.
  • the diameter of the fiber of the fiberized paramylon is not particularly limited, but is, for example, 10 to 500 nm, preferably 20 to 300 nm, and more preferably 50 to 200 nm.
  • the fiber diameter of the fiberized paramylon can be usually measured based on an electron microscopic image of the fiberized paramylon.
  • the subsidence volume of fiberized paramylon in water is not particularly limited, but is, for example, 30 to 300 ⁇ mL / g, preferably 50 to 250 ⁇ mL / g, more preferably 70 to 200 ⁇ mL / g.
  • the subsidence volume in water can be measured in accordance with or according to Test Example 2.
  • Fibrous paramylon has a relatively high resistance to enzymatic degradation.
  • the amount of monomer (glucose) produced by the degradation of ⁇ -glucanase is, for example, 0.1 to 50 mg, preferably 1 to 10 mg per 1 g of fiberized paramylon. This amount can be measured according to or according to Test Example 5.
  • Fibrous paramylon has relatively low solubility in alkaline solutions.
  • fiberized paramylon does not dissolve in 0.1-0.3M aqueous sodium hydroxide solution.
  • “does not dissolve” means, for example, the absorbance (660 nm) of the solution after suspending fibrotic paramylon in the aqueous solution (for example, immediately after 1 hour), for example, 0.1 or more, preferably 1.0 That means that. Solubility can be measured in accordance with or according to Test Example 6.
  • the relative value of the crystallinity of the fiberized paramylon relative to the granular paramylon is, for example, 0.60 to 0.90, preferably 0.65 to 0.80.
  • the degree of crystallinity can be measured according to Test Example 7 or according thereto.
  • the fiberized paramylon may be in a form dispersed in a solvent such as water, or in a dry form. Fibrotic paramylon can be redispersed in water even in dry form.
  • dry form indicates that the water content is 15% by mass or less, preferably 10% by mass or less, more preferably 5% by mass or less.
  • the shape of the paramylon particles is not particularly limited, but is usually a flat spheroid.
  • the particle size distribution of the paramylon particles is not particularly limited, but is, for example, 0.5 to 15 ⁇ m, preferably 1 to 6 ⁇ m.
  • the average particle size of the paramylon particles is not particularly limited, but is, for example, 1 to 10, preferably 2 to 4 ⁇ m.
  • Paramylon particles can be produced by separating, isolating, or purifying from Euglena according to or according to a known method (for example, the method described in Japanese Patent No. 5858832). Paramylon particles can be easily obtained, for example, by collecting cell content components obtained by destroying the cell membrane of Euglena. Moreover, you may refine
  • Defibration treatment does not substantially break the hydrogen bond of ⁇ -1,3 glucan present in paramylon particles (for example, 10% or less, 5% or less, 2% or less of ⁇ -1,3 glucan hydrogen bond)
  • Treatment that can be defibrated (with only 1% or less being cut), or part or all of the ⁇ -1,3-glucan chain present in the paramylon particles or the triple helical structure formed by this
  • a known treatment that can grind (shear) or grind (preferably grind (shear)) fine particles such as paramylon particles can be employed as the defibrating treatment.
  • the defibrating treatment can be performed wet or dry. It is preferable to perform the defibrating treatment in a wet manner because the fiberized paramylon can be more efficiently dispersed in the solution.
  • the solvent used in the wet process is not particularly limited as long as it is a solvent capable of dispersing fiberized paramylon, and water can be preferably used.
  • the defibrating treatment may be one type alone or a combination of two or more types. Further, it may be a partially defibrated paramylon, and is intended by the present invention as long as it includes a defibrated paramylon.
  • each condition (defibration treatment target liquid, clearance, grinding wheel rotation speed, number of times of defibrating treatment) when performing wet defibrating using a mortar mill (supermass colloider) manufactured by Masuyuki Sangyo is as follows: It is as follows.
  • Defibration target liquid A water suspension of paramylon particles.
  • concentration of the paramylon particles is not particularly limited, but is, for example, 0.1 to 40% by mass, preferably 0.5 to 30% by mass, more preferably 1 to 20% by mass, and further preferably 2 to 15% by mass.
  • Grinding wheel rotation speed is, for example, 500 to 3000 rpm, preferably 700 to 2000 rpm, more preferably 800 to 1600 rpm.
  • the fiberized paramylon may be used alone or in combination of two or more.
  • Fibrous paramylon has an effect of improving sugar and / or lipid metabolism, and can therefore be used as an active ingredient of a sugar and / or lipid metabolism improving agent.
  • sugar metabolism includes each of a series of phenomena from ingestion to excretion of sugar.
  • lipid metabolism includes each of a series of phenomena from intake of lipid or a substance that can be converted into lipid to elimination of lipid or a substance converted from lipid.
  • metabolic syndrome is one of three: (1) high blood pressure, (2) high blood glucose level, (3) low HDL cholesterol or high neutral fat It is said that more than one applies.
  • the agent of the present invention can be used in various fields, for example, as a food additive, a food composition (including health promoting agents, nutritional supplements (such as supplements)), and pharmaceuticals.
  • the form of the agent of the present invention is not particularly limited, and can take a form usually used in each application depending on the application.
  • the application is food additives, medicines, health enhancers, nutritional supplements (such as supplements), etc., for example, tablets (orally disintegrating tablets, chewable tablets, effervescent tablets, lozenges, jelly-like drops) Pills, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions, syrups), jelly, etc. .
  • tablets orally disintegrating tablets, chewable tablets, effervescent tablets, lozenges, jelly-like drops
  • Pills granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions, syrups), jelly, etc.
  • liquid, gel or solid food for example, beverages such as juice, soft drink, tea, soup, soy milk, salad oil, dressing, yogurt, jelly, pudding, sprinkle, Examples include infant formula, cake mix, powdered or liquid dairy products, bread and cookies.
  • the agent of the present invention may further contain other components as necessary.
  • the other components are not particularly limited as long as they are components that can be blended in food additives, food compositions, pharmaceuticals, health enhancers, nutritional supplements (such as supplements), etc. , Solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, thickeners, colorants, fragrances, chelating agents and the like.
  • the agent of the present invention may be in a form in which fiberized paramylon is dispersed in a solvent such as water, or in a dry form. Fibrous paramylon can be more easily dispersed in water, even in dry form.
  • the agent of the present invention can be produced by a method including a step of blending fiberized paramylon.
  • the agent of this invention is a drink, for example, the process of mix
  • blending water is further included.
  • fiberized paramylon may be blended with an object that already contains water, or water may be blended after blending fiberized paramylon. When blended, the fiberized paramylon can be dispersed in water even in a dry state.
  • the amount of application (for example, administration, ingestion, inoculation, etc.) of the agent of the present invention to the target organism is not particularly limited as long as it is an effective amount that exhibits a medicinal effect, and is usually the dry weight of fibrinated paramylon that is an active ingredient. In general, it is 0.1 to 10000 mg / kg body weight per day.
  • the above-mentioned application amount is preferably applied at least once a day (for example, 1 to 3 times), and can be appropriately increased or decreased depending on age, disease state, and symptoms.
  • the liquid for 5 flasks was collected, and the collected liquid was centrifuged in a centrifuge tube (500 ⁇ g, 4 minutes, room temperature). The supernatant in the centrifuge tube was once removed and collected. The collected supernatant was put into a centrifuge tube to disperse the precipitate in the centrifuge tube and transferred to a 100 mL graduated cylinder. Further, the collected supernatant was added to a measuring cylinder to make up to 90 mL.
  • Production Example 1 Production of fiberized paramylon 1 Paramylon particles produced by repeating Reference Production Example 1 were mixed with purified water to prepare a paramylon particle suspension. The concentration of paramylon particles in the paramylon particle suspension was 5% by mass. The paramylon particle suspension was wet defibrated under the conditions shown in Table 2 below using a stone mill grinder (Supermass colloider, manufactured by Masuko Sangyo Co., Ltd.) to obtain slurry discharged from the grinder. This wet defibrating treatment was repeated 20 times in total. The finally obtained slurry was used as a fiberized paramylon solution in the test. FIG. 1 shows a microphotograph of the paramylon particle suspension, a fiberized paramylon solution, and an appearance photograph of a vial containing these solutions. In the following charts, fiberized paramylon is sometimes referred to as fibrous paramylon.
  • the paramylon particles were unwound and formed into fibers by wet defibrating treatment. Further, it was confirmed that the fiberized paramylon had a branched structure (branched structure) and a network structure. In addition, as shown in the outer appearance photograph of FIG. 1, in the fiberized paramylon liquid, it was shown that the fiberized paramylon was uniformly dispersed in the liquid.
  • Comparative Production Example 1 Production of Chemically Treated Paramylon
  • the paramylon particles of Reference Production Example 1 were chemically treated using the method described in Japanese Patent Application Laid-Open No. 2011-184592. Specifically, the neutralization treatment was performed by dissolving paramylon particles in 1M NaOH aqueous solution and adding hydrochloric acid aqueous solution after dissolution. A gel-like material was generated by the neutralization treatment. The supernatant obtained by the separation process by centrifugation was removed to obtain a solid content. Since the solid content contains salt (NaCl) from the neutralization treatment, a large amount of water is added to the obtained solid content to disperse the solid content, resulting in a gel-like material, and similarly centrifuged.
  • salt NaCl
  • the salt contained in the gel-like material was removed.
  • the salt removal treatment was repeated until the dry mass of NaCl contained in the gel-like material became 0.1 mass% or less per dry weight of the paramylon particles dissolved in the 1M NaOH aqueous solution, to obtain chemically treated paramylon.
  • the dry weight of NaCl contained in the gel-like material was determined by calculating the NaCl concentration of the supernatant after centrifugation from the electrical conductivity of the supernatant.
  • Test Example 1 Analysis of the structure of fiberized paramylon The structure of the fiberized paramylon of Production Example 1 was observed with an electron microscope. Specifically, it was performed as follows. First, 1.5 times the volume of t-butanol was added to the mixture of fiberized paramylon and water, and the fiberized paramylon was dispersed by a vortex mixer. A part of the obtained dispersion was dropped on a flat plate, and the dropped test liquid was frozen. The frozen product was treated under reduced pressure to evaporate the solvent. The obtained sample was subjected to osmium plasma ion coating (thickness 20 nm) and observed with a scanning electron microscope. Observation images are shown in FIGS.
  • the fiberized paramylon observed in this test had a network structure in which the fibers were intertwined with each other.
  • Test example 2 Measurement of settling volume in water “Supervised by the Japan Dietary Fiber Society, edited by the Japanese Dietary Fiber Society Editorial Board (2008) Dietary fiber-Basics and applications-3rd edition, p. 111, Daiichi Shuppan, Tokyo”
  • the measurement was performed according to the method. Specifically, it was performed as follows. Each sample test sample (paramylon particles (reference production example 1), fiberized paramylon (production example 1), or chemically treated paramylon (comparative production example 1)) is placed in a 25 mL plastic tube with a dry mass. In conversion, 250 mg (fiberized paramylon only, 125 mg) was weighed, and the contents were stirred by shaking the plastic tube vigorously by hand.
  • Experimental animals and rearing conditions> This experiment was conducted with the approval of the Ethics Review Committee in accordance with the “Rules Establishing Methods and Maintenance of Animal Experiment Facilities and Specific Experiment Methods” established by the Animal Experiment Committee of the Faculty of Home Economics, Otsuma Women's University. It was.
  • mice 5-week-old male C57BL / 6J mice (Nippon Charles River) were used. After preliminary breeding for 1 week with solid feed (NMF, manufactured by Oriental Yeast Co., Ltd.), groups were divided into 10 groups per group so that the body weight was uniform (however, the standard feed breeding group was 5 animals).
  • NMF solid feed
  • the feed used for the test is as follows. 20% lard was added to the feed of the control group and the test group so that the fat energy ratio was 50%. To the feed of the control group, 5% cellulose was added as dietary fiber.
  • 5% cellulose was added as dietary fiber.
  • For the feed of the test group Euglena gracilis EOD-1 strain dry powder (hereinafter referred to as biomass group), paramylon particles (reference production example 1) (hereinafter referred to as paramylon group), or fiberized paramylon (production example 1) is doubled.
  • the dried fiberized paramylon obtained by mixing with dextrin and freeze-dried hereinafter referred to as fiberized paramylon group was added. Each feed was added in consideration of the water content so that the dry weight would be 5%.
  • a group for ingesting a standard feed to which lard or the like was not added was also prepared.
  • Glucose tolerance measurement> After the fasting from 8 o'clock in the morning for 8 hours in the last week of breeding, a 20% glucose solution was administered into the stomach of the mouse using a gastric sonde so that the body weight was 1 g / kg body weight. Blood was collected from the tail before administration (0 minutes), and blood was similarly collected 15 minutes, 30 minutes, 60 minutes, and 120 minutes after administration. For quantification of the blood glucose level, “Small blood glucose meter Glutest Ace R” (manufactured by Sanwa Scientific Research Institute) was used.
  • the biomass group and the paramylon group showed a slight suppression tendency compared to the control group, whereas the fibrotic paramylon group showed markedly suppressed weight gain compared to the control group. It was.
  • the fibrotic paramylon group has the same level of weight gain as the group fed the standard feed without lard (standard group), despite continuing to eat the lard-added feed. Met.
  • the biomass group and the paramylon group had a lower blood glucose level after glucose administration than the control group, but a significant difference was observed 120 minutes after administration.
  • the fibrotic paramylon group has a lower blood glucose level after glucose administration than the biomass group and the paramylon group, and it can be seen that the increase in blood glucose level is significantly suppressed compared to the control group.
  • a significant difference from the control group was observed at an earlier stage (15 minutes after administration), and it was confirmed that the blood glucose level was significantly lower after 60 minutes after administration.
  • the fiberized paramylon group continues to ingest the feed to which lard was added, the glucose tolerance (blood glucose level after administration of glucose) was the group ingested the standard feed to which lard was not added It was the same level as (standard group).
  • the biomass group and the paramylon group had the same amount of visceral fat as the control group, whereas the fibrotic paramylon group had significantly less visceral fat than the control group. .
  • the visceral fat amount of the fiberized paramylon group tended to be significantly less or less than the biomass group and the control group.
  • the paramylon group tended to be less than the control group, and the fibrotic paramylon group was significantly less than the control group.
  • the fiberized paramylon was significantly less than the control group, biomass group, and paramylon group for the retroabdominal wall fat and the fat around the testicles.
  • the liver weight of the fibrotic paramylon group was significantly smaller than that of the control group. This is presumed to be due to a small amount of fat accumulated in the liver.
  • the cecal weight of the fibrotic paramylon group was significantly higher than that of the control group, and the biomass group and paramylon group also showed a tendency to be higher than that of the control group.
  • the increase in cecal weight suggests that fibrotic paramylon is broken down in the intestinal bacteria of the large intestine to produce short chain fatty acids.
  • This short-chain fatty acid is known to have an anti-obesity action and the like (for example, Japanese Patent Application Laid-Open No. 06-256402).
  • the total cholesterol is significantly less fibrotic paramylon compared to the control group, the biomass group, and the paramylon group, the paramylon group is significantly smaller than the control group, and the biomass group is smaller than the control group.
  • the trend was low.
  • LDL cholesterol was also significantly less in the fibrotic paramylon group than in the control group.
  • the NEFA value of the fibrotic paramylon group was significantly reduced as compared with the control group (high fat diet group).
  • NEFA value is an abbreviation of Non-esterified fatty acid, and is a non-ester type fatty acid released into the blood when neutral fat of adipose tissue is degraded by hormone-sensitive lipase. Insulin is known as one of the inhibitors of the action of hormone-sensitive lipase. When a glucose metabolism disorder such as a decrease in insulin secretion or insulin action occurs, adipose tissue degradation by hormone-sensitive lipase increases and NEFA increases. It is considered. In addition, NEFA has a surface-active effect, and when the blood concentration is high, it dissolves the cell membrane and destroys the cells, which is considered to be one of the causes of organ dysfunction.
  • NEFA in the fibrotic paramylon group was significantly lower than that in the control group (high-fat diet group), suggesting the possibility of inhibiting glucose metabolism disorder. Moreover, it was suggested that the risk of developing organ dysfunction may be reduced by suppressing the increase in NEFA.
  • the serum ALT concentration in the fibrotic paramylon group was significantly lower than that in the control group.
  • the serum ALT concentration in the fibrotic paramylon group tended to be lower than that in the biomass group and the control group.
  • ALT is considered to be a component that is released into the blood when liver cells break down, and it is thought that when fat accumulates in the liver, liver cells break down and ALT is released. It was suggested that damage can be suppressed.
  • the CRP value of the fiberized paramylon group was significantly less than that of the control group, and showed a tendency to be lower than that of the biomass group and paramylon group.
  • CRP is an abbreviation for C-reactive protein. It is a protein that increases in serum when inflammation or tissue cell destruction occurs, and serves as an index of inflammation. It is known that when chronic inflammation occurs and the value of CRP increases, insulin resistance deteriorates and blood glucose level rises. In addition, it is said that CRP shows a mild high level in diabetes, obesity, hyperlipidemia etc. which are considered as atherosclerotic disease and its risk state, and when metabolic syndrome and hypercholesterolemia overlap in people with high CRP, It has been shown that it is prone to heart disease and stroke. As shown in FIG. 17, in the group in which fibrotic paramylon was administered to a high-fat diet, the CRP concentration was significantly lower than that in the control group (high-fat diet group), and insulin resistance, increased blood glucose level, etc. This suggests the possibility of reducing the risk.
  • the leptin value was significantly less in the fibrotic paramylon group than in others.
  • Leptin is an adipocytokine (a physiologically active substance) secreted from white adipocytes, which transmits a powerful satiety signal, resulting in increased energy consumption due to increased sympathetic nerve activity, controlling obesity and controlling weight gain. Play a role.
  • leptin production increases as the adipose tissue increases, so the blood leptin level is rather high. Accordingly, obese people become so-called “leptin-resistant” states in which eating disorders are not observed regardless of high leptin levels, and obesity is increasingly promoted. It is also considered that this leptin resistance may trigger insulin resistance.
  • blood leptin levels are higher in hypertensive diseases than in normal individuals, and it has been reported that blood leptin levels correlate with blood pressure.
  • the insulin concentration was significantly lower in the fibrotic paramylon group than in the control group, although the blood glucose concentration was not so different between the groups. This suggests that the sensitivity to insulin is increased in the fiberized paramylon intake group, in other words, insulin resistance is improved.
  • the biomass group and the paramylon group also show a tendency that the insulin concentration is lower than that of the control group, and the insulin resistance tends to be improved in the same manner.
  • fibrotic paramylon group may be used as a diabetes preventive or therapeutic agent because it improves insulin resistance and suppresses an increase in blood glucose level.
  • Test Example 4 Sugar diffusion inhibition test 1 The amount of sugar in the solution that diffuses and permeates the semipermeable membrane was compared with and without fibrotic paramylon. This test was conducted with reference to a previously published document (J. Agric. Food Chem. 2001, 49, 1026-1029). Specifically, it was performed as follows.
  • Test Example 5 Evaluation Test for Degradation Resistance by Enzyme Degradation resistance by ⁇ -glucanase was evaluated by measuring the amount of monomer produced. Specifically, it was performed as follows.
  • Test Example 6 Evaluation of solubility in alkaline solution The solubility in alkaline solution was evaluated. Specifically, it was performed as follows.
  • Test method Substance to be tested (paramylon particles (reference production example 1) pulverized into powder, fiberized paramylon (production example 1), chemically treated paramylon (comparative production example: dissolved in 1.0M NaOH aqueous solution)) 250 mg ( (Dry weight) was suspended in 10 mL of a test solution (pure water, 0.1 M NaOH aqueous solution, 0.3 M NaOH aqueous solution, 1 M NaOH aqueous solution) in a vial. After the vial was shaken vigorously by hand for 20 seconds and after shaking for 1 hour at 80 rpm on a shaker, the absorbance at 660 nm of the liquid in the vial was measured. The absorbance was measured using a spectrophotometer V-730 manufactured by JASCO Corporation.
  • Production Example 2 Production of fiberized paramylon 2 Using a bead mill, a shear force was applied to the paramylon particles (Reference Production Example 1) to fiberize the paramylon particles to produce a liquid additive (dispersion) containing fiberized paramylon.
  • the defibrating treatment with a bead mill was performed under the general operating conditions used for submicron grinding.
  • the raw material solution containing 10% by mass of paramylon particles was defibrated by a bead mill.
  • the obtained fiberized paramylon was observed with an electron microscope. An observation image is shown in FIG.

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Abstract

La présente invention aborde le problème de la fourniture d'un agent améliorant le métabolisme des sucres et/ou des lipides. Le problème est résolu par un agent améliorant le métabolisme des sucres et/ou des lipides qui contient du paramylon fibreux.
PCT/JP2018/007625 2017-03-02 2018-02-28 Agent améliorant le métabolisme des sucres et/ou des lipides WO2018159714A1 (fr)

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Cited By (3)

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WO2020054090A1 (fr) * 2018-09-11 2020-03-19 株式会社神鋼環境ソリューション Agent améliorant le métabolisme des sucres et/ou des lipides
JP2020083873A (ja) * 2018-11-21 2020-06-04 株式会社神鋼環境ソリューション ＰＰＡＲα発現量増進剤
JP2020158460A (ja) * 2019-03-27 2020-10-01 株式会社神鋼環境ソリューション マクロファージ活性化剤

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JP6431008B2 (ja) 2016-07-14 2018-11-28 ファナック株式会社 放電加工機および故障判定方法

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JP2014118374A (ja) * 2012-12-14 2014-06-30 Euglena Co Ltd 糖尿病抑制剤
WO2015156339A1 (fr) * 2014-04-08 2015-10-15 株式会社ユーグレナ Agent d'ajustement de l'équilibre immunitaire
JP2016199650A (ja) * 2015-04-08 2016-12-01 株式会社ユーグレナ 加工β−グルカン及びその製造方法
JP2017019866A (ja) * 2016-10-21 2017-01-26 株式会社ユーグレナ 糖尿病抑制用食品
JP2018035102A (ja) * 2016-09-01 2018-03-08 株式会社神鋼環境ソリューション 抗肥満剤

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Publication number Priority date Publication date Assignee Title
JP2014118374A (ja) * 2012-12-14 2014-06-30 Euglena Co Ltd 糖尿病抑制剤
WO2015156339A1 (fr) * 2014-04-08 2015-10-15 株式会社ユーグレナ Agent d'ajustement de l'équilibre immunitaire
JP2016199650A (ja) * 2015-04-08 2016-12-01 株式会社ユーグレナ 加工β−グルカン及びその製造方法
JP2018035102A (ja) * 2016-09-01 2018-03-08 株式会社神鋼環境ソリューション 抗肥満剤
JP2017019866A (ja) * 2016-10-21 2017-01-26 株式会社ユーグレナ 糖尿病抑制用食品

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020054090A1 (fr) * 2018-09-11 2020-03-19 株式会社神鋼環境ソリューション Agent améliorant le métabolisme des sucres et/ou des lipides
JPWO2020054090A1 (ja) * 2018-09-11 2021-08-30 株式会社神鋼環境ソリューション 糖及び／又は脂質の代謝改善剤
JP7231163B2 (ja) 2018-09-11 2023-03-01 株式会社神鋼環境ソリューション 糖及び／又は脂質の代謝改善剤
JP2020083873A (ja) * 2018-11-21 2020-06-04 株式会社神鋼環境ソリューション ＰＰＡＲα発現量増進剤
JP2020158460A (ja) * 2019-03-27 2020-10-01 株式会社神鋼環境ソリューション マクロファージ活性化剤
JP7229829B2 (ja) 2019-03-27 2023-02-28 株式会社神鋼環境ソリューション マクロファージ活性化剤

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