JP2010241713A - Inhibitor against increase in blood gip level and/or blood insulin level - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an inhibitor against increase in a blood GIP level and/or a blood insulin level (preventive and ameliorating agent for diabetes) that does not deteriorate the blood sugar level. <P>SOLUTION: There are provided an oral administration preparation, a blood GIP level increase inhibitor, a blood insulin level increase inhibitor, a preventive and ameliorating agent for diabetes, each comprising a β-chitin nanofiber. The β-chitin nanofiber has preferably an average fiber width of at most 100 nm. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a blood GIP and / or blood insulin increase inhibitor capable of reducing blood concentrations of insulin, GIP and the like.

  Gastric inhibitory polypeptide (GIP) is a gastrointestinal hormone that enhances glucose-dependent insulin secretion, and it is known that secretion is enhanced by lipids in the diet during feeding. Moreover, since GIP is known to have gastric acid secretion inhibitory action and gastric motility inhibitory action (Non-Patent Documents 1 to 3), substances that reduce blood GIP are effective in promoting digestion and improving stomach leaning. It is considered useful. As a result of research so far, 3-bromo-5-methyl-2-phenylpyrazolo [1,5-a] pyrimidin-7-ol (BMPP) is known as a substance that inhibits the function of GIP. Gua gum etc. are known as what reduces a GIP density | concentration (patent document 1, nonpatent literature 4-9).

  However, BMPP has not been confirmed to have an inhibitory effect on GIP function in vivo, and guagum has a problem that the effect of suppressing blood GIP elevation during lipid intake has not been studied. It is not necessarily sufficient in terms.

  When blood sugar rises, insulin is secreted from pancreatic β cells of the pancreas, sugar uptake into fat and muscle is promoted, fat synthesis in fat tissue and muscle is promoted, and decomposition and combustion are suppressed. However, if the patient becomes hyperglycemic and continues to secrete insulin, insulin sensitivity decreases (insulin resistance) in the target organs of skeletal muscle, liver, and adipose tissue, and more insulin is secreted from the pancreas. Will come to be. However, even if insulin secretion increases, the target organ produces insulin resistance, and thus follows a vicious circle in which a hyperglycemic state continues.

  If such insulin secretion is repeated, the pancreas will eventually become exhausted and insulin secretion from the pancreatic β cells will decrease, but the insulin resistance of each target organ will remain increased and high. It becomes a blood sugar state. Thus, it is known that if the insulin action mechanism does not function well, it will eventually become a constitution that is likely to cause diabetes or the like, and diabetes will worsen.

  On the other hand, when the secretion of GIP increases, in addition to causing indigestion and stomach sag, it also becomes a factor that promotes the secretion of insulin.

  Chitin is known to have a cell immunity stimulating action (Non-patent Document 10), promotion of lipid excretion into feces (Non-Patent Document 11), and anti-obesity action by long-term ingestion (Non-Patent Document 11). In addition, the effects obtained by changing the structure of chitin include, for example, a low molecular weight chitin obtained by decomposing chitin, which has an anti-obesity action (Patent Document 2), and deacetylated β-chitin derived from bandit bones. Chitosan has been found to have an effect of suppressing blood cholesterol and improving obesity (Patent Document 3). However, the effect of chitin to suppress the elevation of hormones such as blood GIP and insulin and the accompanying diabetes prevention / amelioration effect are not known.

  An example of using chitin having a fiber width of micron / nano order as food is chitin / chitosan obtained from Geotrichum spp. The fiber width of the fibers obtained from the cells is 5 μm on average and 1,000 μm in length (Patent Document 4). In addition, Special Table 2002-536507 mentions a method of derivatizing microfibers sterically / electrostatically from polysaccharides such as cellulose and chitin, and mayonnaise and dressing compositions using the same, but derivatization There is no description regarding the fiber width (Patent Document 5). Furthermore, none of the physiological effects on GIP, insulin, and diabetes have been shown.

International Publication No. 01/87341 Pamphlet Japanese Patent No. 2605300 Japanese Patent No. 3807464 JP 2007-159568 A Japanese Patent Laid-Open No. 2002-536507

J.C.Brown et al., Canadian J Physiol Pharmacol 47: 113-114, 1969 J. M. Falko et al., J Clin Endocrinol Metab 41 (2): 260-265, 1975 Toshiji Oda et al., Gastrointestinal function and pathology, 1981, Chugai Medical, P205-216 Gagenby S J et al., Diabet Med. 1996 Apr; 13 (4): 358-64 Ellis PR et al., Br J Nutr. 1995 Oct; 74 (4): 539-56 Simoes Nunes C et al., Reprod Nutr Dev. 1992; 32 (1): 11-20 Morgan LM et al., Br J Nutr. 1990 Jul; 64 (1): 103-10 Requejo F et al., Diabet Med. 1990 Jul; 7 (6): 515-20 Morgan et al., Br J Nutr. 1985 May; 53 (3): 467-75 Inoue Kuniyo et al., Development of functional carbohydrate materials and food applications, 2005, CMC Publishing, P387-393 Han, L.-K et al., International Journal of Obesity. 1999; 23 (2): 174-179 Hara et al., I, Ibaraki. 2008.7; 57 (7): 1094-1097

  An object of the present invention is to provide a blood GIP and / or blood insulin elevation inhibitor that can reduce blood concentrations of insulin, GIP, and the like.

  Another object of the present invention is to provide a diabetes preventive / ameliorating agent capable of reducing blood insulin without worsening blood glucose.

  The present invention provides an orally-administered agent, a blood GIP (Gastric inhibitory polypeptide) elevation inhibitor, a blood insulin elevation inhibitor, and a diabetes preventive / ameliorating agent comprising β-chitin nanofibers.

  The blood GIP and / or blood insulin elevation inhibitor containing the β-chitin nanofibers of the present invention can reduce blood concentrations of insulin, GIP and the like.

  The diabetes preventive / ameliorating agent containing β-chitin nanofiber of the present invention can reduce blood insulin without worsening blood glucose.

It is a figure for demonstrating the influence on the blood glucose level of the beta-chitin nanofiber in Example 1. FIG.

<Production of β-chitin nanofiber>
The β-chitin nanofiber used in the present invention is obtained by a production method having a step of immersing β-chitin in an acidic liquid having a pH of 5 or less and a step of defibrating the β-chitin in a state of being immersed in the acidic liquid. be able to.

  First, the process of immersing β-chitin in an acidic liquid having a pH of 5 or less will be described. The β-chitin used as a raw material is preferably purified β-chitin having a crystallinity of 90% or less, and more preferably β-chitin having a crystallinity of 60 to 85%. The crystallinity in this case is the crystallinity expressed as (Ia-Ib) / Ia × 100, where the peak intensity at 20 ° of the X-ray diffraction pattern is Ia and the peak intensity of the amorphous part at 15 ° is Ib. is there.

  The purified β-chitin is preferably derived from squid, and particularly obtained from squid tendon.

  As the purified β-chitin, an alkali purified product purified using the following alkali or an alkali purified-acid purified product obtained by further acid purification after alkali purification can be used.

  The alkaline purified product is obtained by immersing a pulverized product of β-chitin in an aqueous solution of 0.1 to 8 mol / L alkali (for example, sodium hydroxide) for 1 to 100 hours, followed by filtration on a mesh, and β- Chitin is obtained by washing with ion exchange water. The standard of the cleaning is preferably until the conductivity of the cleaning liquid is 0.5 m / s or less.

Alkaline refining-acid refined product is obtained by immersing the alkali refined product obtained by the above method in an aqueous solution of 0.01 to 5 mol / L acid (for example, hydrochloric acid) for 1 to 100 hours, followed by filtration on the mesh, The above β-chitin is obtained by washing with ion exchange water. The standard of the cleaning is preferably until the conductivity of the cleaning liquid is 0.5 m / s or less.
There is no restriction | limiting in particular in the acid used for alkali refining-acid refined product. As the organic acid, formic acid, acetic acid, citric acid and the like can be used, and as the inorganic acid, hydrochloric acid, sulfuric acid, nitric acid and the like can be used. These acids may be used alone or in combination.

  The acidic solution used in the step of immersing β-chitin in an acidic liquid having a pH of 5 or lower is an aqueous solution selected from organic acids and inorganic acids, but formic acid, acetic acid, citric acid, etc. can be used as the organic acid. As the acid, hydrochloric acid, sulfuric acid, nitric acid and the like can be used. There is no restriction as long as it is an acidic liquid having a pH of 5 or less, and it may be used alone or in combination. As the acidic liquid used in this step, acetic acid and hydrochloric acid are particularly preferable.

  The pH of the acidic solution for defibrating the β-chitin may be 5 or less, but the pH is preferably in the range of 2-4.

  The amount ratio of β-chitin and acidic solution is not particularly limited, but it is preferable that β-chitin is completely immersed in the acidic solution, and is adjusted in consideration of ease of defibrating treatment in the subsequent step. .

  The temperature of the acidic solution is not particularly limited and is usually room temperature (20 to 25 ° C.), but may be heated or cooled as necessary.

  Next, the step of defibrating the β-chitin while immersed in an acidic solution will be described.

  The defibrating process may be any method that can unwind the fibers by applying physical force to β-chitin. For example, a disaggregator, a beating machine, a low-pressure homogenizer, a high-pressure homogenizer, a grinder, a cutter mill, a ball mill Jet mills, short screw extruders, twin screw extruders, ultrasonic stirrers, household juicer mixers, and the like can be used.

  If the homogenizer of Production Example 1 is immersed in 0.5 g of purified β-chitin in 100 g of an acidic solution, the defibration treatment may be performed at a rate of 5000 to 20000 r / m for 1 to 30 minutes.

  By this fibrillation treatment, β-chitin nanofibers having a width of 2 to 100 nm and a length of 500 nm or more (preferably 700 nm or more) can be obtained.

  When the manufacturing method including the above two steps is applied, it is considered that β-chitin nanofiber can be obtained for the following reason.

  The step of immersing β-chitin in an acidic liquid having a pH of 5 or less imparts a positive charge to glucosamine, which is considered to be present on the surface of chitin nanofibrils constituting β-chitin, thereby causing charge repulsion between the chitin nanofibrils. Give rise to In the subsequent defibrating step, β-chitin is defibrated, so that the bonds between the chitin nanofibrils can be easily broken to obtain β-chitin nanofibers.

  The β-chitin nanofabric obtained by such a production method is considered to be medically safe because the glucosamine unit part originally present in chitin is only charged and not chemically modified. It is done.

<A blood GIP and/or blood insulin rise inhibitor containing β-chitin nanofibers and a diabetes preventive/ameliorating agent containing β-chitin nanofibers>
Hereinafter, the blood GIP and / or blood insulin elevation inhibitor and the diabetes preventive / ameliorating agent of the present invention will be described. Hereinafter, these may be collectively referred to as “the drug of the present invention”.

  The chemical | medical agent of this invention contains the beta-chitin nanofiber obtained by the said manufacturing method as an active ingredient.

  The diameter (width) of the “nanofiber” is an example of what is called a nanofiber for a fiber with a submicron order (100 to 10,000 nm) or larger diameter (width) (Akihiko Tanioka, Fiber and Industry, P129-130, 59 (4) 2003), β-chitin nanofibers used in the present invention were prepared in a 0.1% by mass suspension and a glass filter with an opening of 16 μm (25G P16, manufactured by SHIBATA) When suction filtration is performed, the 1% by mass or more of β-chitin nanofibers contained in the suspension is filtered. When β-chitin nanofibers are aggregated, it is difficult to filter, and therefore, those obtained in Comparative Production Examples 1 and 2 described in Examples described later do not satisfy the above requirements.

  The β-chitin nanofibers contained in the drug of the present invention preferably have an average fiber width of 100 nm or less, more preferably 2 to 80 nm, and even more preferably 3 to 60 nm.

  The β-chitin nanofibers contained in the drug of the present invention preferably have an average fiber length of 40000 nm or less, more preferably 500 to 30000 nm, and still more preferably 700 to 20000 nm.

  The drug of the present invention can be made into a desired form such as tablet, granule, powder, liquid (suspension), gel or the like depending on the form of use.

  For solids such as tablets, granules, and powders, β-chitin nanofibers alone may be used, and excipients, binders, disintegrants, lubricants, colorants that can be used in foods and pharmaceuticals , Flavoring agents, flavoring agents and the like can be blended and molded using a desired molding machine (tablet press, granule manufacturing machine, spray dryer, etc.).

  When liquid (suspension) is used, water alone may be used, and together with water, other organic solvents that can be used in food (for example, ethanol), aqueous surfactants, aqueous acids, aqueous bases, etc. A mixed solvent may be used. When gelled, a thickener or the like can be added and blended.

  The GIP and / or insulin elevation inhibitor of the present invention is desirably taken before a meal, together with or after a meal, and the intake amount as β-chitin nanofabric is about 0.002 to 2 g per kg body weight. / Day is preferred.

  The agent for preventing / ameliorating diabetes of the present invention is preferably taken before a meal, or together with or after a meal, and the intake amount as β-chitin nanofiber is about 0.002 to 2 g / kg of body weight. preferable.

  The drug of the present invention can be administered to humans and animals, and can be ingested by being blended with various foods and drinks, pharmaceuticals, quasi drugs, pet foods and the like. The food can be applied to functional foods, foods for the sick, and foods for specific health, which are based on the concept of hormone secretion suppression effect or diabetes prevention / improvement effect, and display the effect as necessary. Although the form of a drink is not specifically limited, For example, it can mix | blend with all drinks, such as a fruit juice drink, a carbonated drink, a tea-type drink, a milk drink, an alcoholic drink, a soft drink, and it can be used for manufacture. Moreover, it can mix | blend with all food forms, such as jelly-like foodstuffs, various snacks, baked confectionery, cakes, chocolate, gum, candy, a tablet, a capsule, soup, and can be used for manufacture.

  The medicament of the present invention is orally administered as a pharmaceutical in solid dosage forms such as tablets and powders or liquid dosage forms such as elixirol, syrups and suspensions. When preparing an oral solid preparation, after adding an excipient, a binder, a disintegrant, a lubricant, a coloring agent, a corrigent, a corrigent and the like to the agent of the present invention as necessary. A tablet, coated tablet, granule, powder, capsule or the like can be produced by a conventional method. Moreover, when preparing an oral liquid formulation, it can manufacture by a conventional method, adding a flavoring agent, a buffering agent, a stabilizer, etc.

  The drug of the present invention is administered in the form of a nutritional composition such as an enteral nutrient for elderly persons who are difficult to supplement with an appropriate amount of nutrients or are sick in bed rest.

Production Example 1 (Production of β-chitin nanofiber)
(I) Raw materials and purification agents β-chitin: β-chitin pulverized product (manufacturer: Dainichi Seika Co., Ltd.)
Sodium hydroxide (1 mol / l): Commercial product (Manufacturer: Wako Pure Chemical Industries, Ltd.)
Hydrochloric acid (0.1 mol / l): Commercial product (manufacturer: Kanto Chemical Co., Inc.).
(II) Production Procedure First, 30 g of the above-mentioned β-chitin pulverized product was immersed in 500 g of 1 mol / l sodium hydroxide for 24 hours, filtered through a mesh, and the β-chitin pulverized product remaining on the mesh was Using ion-exchanged water, the filtrate was sufficiently washed until the electrical conductivity of the filtrate was 0.5 ms / s or less to obtain an alkaline purified product of β-chitin.

  Next, after adjusting the pH of a suspension of 0.5 g of β-chitin alkali purified product and 100 g of ion-exchanged water to 3.0 with hydrochloric acid, using a homogenizer (Excel Auto Homogenizer, Nippon Seiki Seisakusho Co., Ltd.) The pulverized product was refined by stirring for 5 minutes to obtain a translucent suspension of β-chitin nanofibers. Finally, the pH of the suspension was adjusted to 6.5. The average fiber width of the obtained β-chitin nanofibers was 54.5 nm, the average fiber length was 19.1 μm, and the content of β-chitin nanofibers in the suspension was 11.8%.

Production Example 2 (Production of β-chitin nanofiber)
30 g of the alkaline purified product of β-chitin obtained in Production Example 1 was immersed in 500 g of 0.1 mol / l hydrochloric acid for 24 hours, filtered through a mesh, and the β-chitin alkaline purified product remaining on the mesh was removed. Then, using ion-exchanged water, the filtrate was sufficiently washed until the electrical conductivity of the filtrate became 0.5 ms / s or less, to obtain an alkali purified β-chitin purified product.

  Next, the pH of a suspension of 0.5 g of β-chitin purified with acid-purified product and 100 g of ion-exchanged water was adjusted to 3.0 with hydrochloric acid, and then homogenizer (Excel Auto Homogenizer, Nippon Seiki Seisakusho Co., Ltd.) ), The pulverized product was refined by stirring for 5 minutes to obtain a translucent suspension of β-chitin nanofibers. Finally, the pH of the suspension was adjusted to 6.5. The obtained β-chitin nanofibers had an average fiber width of 51.9 nm, an average fiber length of 14.8 μm, and a β-chitin nanofiber content in the suspension of 25%.

Comparative Production Example 1 (Production of β-chitin non-nanofiber)
The suspension of β-chitin nanofibers obtained in Production Example 1 was stored at room temperature for about 2 months and aggregated over time. Since the average fiber width of the obtained fiber was 160 nm and the average fiber length was 54.2 μm, which was about three times that of Production Example 1, in comparison with Production Example 1, β-chitin non-nanofiber was obtained. . The nanofiber content in the suspension was 0%.

Comparative Production Example 2 (Production of β-chitin non-nanofiber)
The suspension of β-chitin nanofibers obtained in Production Example 2 was stored at room temperature for about 2 months and aggregated over time. Since the average fiber width of the obtained fiber was 152 nm and the average fiber length was 49.5 μm, which was about three times that of Production Example 2, it was determined as β-chitin non-nanofiber in comparison with Production Example 2. . The nanofiber content in the suspension was 0%.

  Methods for measuring physical properties of β-chitin nanofibers and β-chitin non-nanofibers are as follows.

(1) Properties of suspension [mass fraction of nanofibers in β-chitin suspension (β-chitin nanofiber content) (%)]
A β-chitin suspension was prepared to 0.1% by mass, and its solid content concentration was precisely measured. Subsequently, the β-chitin suspension was subjected to suction filtration with a glass filter having a mesh size of 16 μm (25GP16, manufactured by SHIBATA), and then the solid content concentration of the filtrate was precisely measured. The (C1 / C2) value obtained by dividing the solid content concentration (C1) of the filtrate by the solid content concentration (C2) of the suspension before filtration was calculated as the nanofiber content (%).

(2) Fiber shape (2-1) Average fiber width The average fiber width of β-chitin nanofibers was measured by dropping a suspension diluted to 0.0001% by mass onto mica and drying it as an observation sample. The fiber height was measured with an atomic force microscope (Nanoscope III Tapping mode AFM, manufactured by Digital instrument, using a probe made by Nano Sensors, Point Probe (NCH)). In an image in which β-chitin fibers can be confirmed, five or more were extracted, and the average fiber width was determined from the fiber height.

（The Theory of Polymer Dynamics, Ｍ.DOI and D.F.EDWARDS， CLARENDON PRESS・OXFORD,1986,P312に記載の剛直棒状分子の粘度式（８．１３８）を利用した（ここでは、剛直棒状分子＝β−キチンナノファイバーとした）。（８．１３８）式と Ｌｂ²×ρ₀＝M/N_Aの関係から数式１が導出される。ここで、η_spは比粘度、πは円周率、lnは自然対数、Pはアスペクト比（L/ｂ）、γ＝0.8、ρ_sは分散媒の密度（ｋｇ/ｍ³）、ρ₀はβ−キチンナノファイバー結晶の密度（ｋｇ/ｍ³）を1.5とし、Cはβ−キチンナノファイバーの質量濃度（C＝ρ/ρ_s）、Lは繊維長、ｂは繊維幅（β−キチンナノファイバー断面は正方形とする）、ρはβ−キチンナノファイバーの濃度（ｋｇ/ｍ³）、Ｍは分子量、N_Aはアボガドロ数を表す）。 (2-2) Average fiber length The average fiber length was calculated from the viscosity of a dilute suspension (0.005 to 0.04 mass%) obtained by diluting β-chitin nanofibers with water. The viscosity was measured at 20 ° C. using a rheometer (MCR300, DG42 (double cylinder), manufactured by PHYSICA). From the relationship between the mass concentration of β-chitin nanofibers and the specific viscosity of β-chitin nanofiber suspension with respect to water, the aspect ratio of β-chitin nanofibers is calculated by the following formula and the average fiber length of β-chitin nanofibers is calculated. Say it.

(The theory of polymer dynamics, M.DOI and DFEDWARDS, CLARENDON PRESS · OXFORD, 1986, P312) The viscosity formula (8.138) of a rigid rod-like molecule was used (here, rigid rod-like molecule = β-chitin nano and with the fiber). (8.138) equation 1 from the relationship between the expression and _{^{Lb 2 × ρ 0 = M /}} N a is derived. here, eta _sp is specific viscosity, [pi is circle ratio, ln is a natural Logarithm, P is aspect ratio (L / b), γ = 0.8, ρ _s is dispersion medium density (kg / m ³ ), ρ ₀ is β-chitin nanofiber crystal density (kg / m ³ ) 1.5 , C is β-chitin nanofiber mass concentration (C = ρ / ρ _s ), L is fiber length, b is fiber width (β-chitin nanofiber cross section is square), ρ is β-chitin nanofiber concentration (kg / m ^3), M is the molecular weight, the N _a represents Avogadro's number).

Example 1 Effects of β-chitin nanofibers on blood insulin, blood GIP and blood glucose level GIP and insulin when β-chitin nanofibers are provided as a blood GIP and / or a post-blood insulin rise inhibitor The rise inhibitory effect was tested.

1-1 Test Sample The β-chitin nanofibers of Production Example 1 and Production Example 2 were used as test samples.

1-2 Test animals
Seven-week-old male mice C57BL / 6J Jcl (CLEA Japan) were used. Each group was N = 4.

1-4 胃内投与試験（血糖、血中インスリン、血中GIP測定）
16時間絶食させたマウスをエ−テル麻酔下、眼窩静脈よりヘパリン処理ヘマトクリット毛細管（VITREX製）を用い、初期採血を行った。その後、試験試料を経口ゾンデ針にて経口的に胃内投与し、10分、30分、1時間、2時間後にエーテル麻酔下、眼窩静脈より採血を行った。 1-3 Preparation and dosage of administration sample Glucose (manufactured by Kanto Chemical) and triolein (manufactured by Sigma), lecithin (manufactured by egg) (manufactured by Wako Pure Chemical Industries) and albumin (manufactured by bovine serum) (manufactured by Sigma) It was emulsified to prepare an emulsion. Using this emulsion as a control, the β-chitin nanofiber of the present invention was added to prepare a sample for intragastric administration. Table 1 shows the dosage for animals.

1-4 Intragastric administration test (blood glucose, blood insulin, blood GIP measurement)
Mice fasted for 16 hours were subjected to initial blood collection using an heparinized hematocrit capillary tube (manufactured by VITREX) from the orbital vein under ether anesthesia. Thereafter, the test sample was orally administered to the stomach with an oral sonde needle, and blood was collected from the orbital vein under ether anesthesia 10 minutes, 30 minutes, 1 hour, and 2 hours later.

  After blood collection, the blood glucose level was measured immediately using a portion of the blood using a simple blood glucose meter (glucose dehydrogenase / potential difference measurement method, manufactured by Roche Diagnostick). Blood collected with a heparinized hematocrit capillary tube was stored under ice cooling until plasma separation, and then centrifuged at 11000 rpm for 5 minutes to obtain plasma. GIP and insulin were measured from the obtained plasma.

  Blood GIP concentration is measured by Rat / Mouse GIP (Total) ELISA kit (Linco Research / Millipore co., ELISA method). Blood insulin concentration is measured by insulin measurement kit (Morinaga Biochemical Laboratory, ELISA method). ).

表２、表３の結果から、本発明品のβ-キチンナノファイバー投与群は、コントロール投与群に比べて食後の最大ＧＩＰ値（Δ10分値）及び最大インスリン値（Δ10分値）が低かった。この結果から、本発明品のβ-キチンナノファイバーは、血中ＧＩＰの上昇抑制、血中インスリンの上昇抑制効果を有することが分かった。 1-5 Results The maximum blood GIP value after sample administration and the maximum blood insulin value (the maximum value is 10 minutes for both blood GIP and blood insulin) and the difference between them (Δ10 minute value) are calculated. Tables 2 and 3 show the results. For statistically significant differences between groups, a t-test (two-sided test) is performed on the control administration group. When the significance level is less than 10%, the P value is used. When the significance level is 10% or more, NS (Non-Significant) is used. Indicated.

From the results of Tables 2 and 3, the β-chitin nanofiber administration group of the present invention product had lower maximum GIP value (Δ10 min value) and maximum insulin value (Δ10 min value) after meal compared to the control administration group. . From this result, it was found that the β-chitin nanofiber of the present invention has an effect of suppressing the increase of blood GIP and the effect of suppressing the increase of blood insulin.

  In addition, the time course of blood glucose level after administration is shown in FIG. In the β-chitin nanofiber administration groups of Production Examples 1 and 2, no significant increase in blood glucose level was observed compared to the control administration group.

  Since insulin is a hormone that lowers blood glucose levels, reducing blood insulin is a concern that blood glucose levels will increase significantly. However, as shown in FIG. 1, the β-chitin nanofiber administration group of Production Examples 1 and 2 showed almost the same change in blood glucose level as that after control administration. It became clear that blood insulin could be reduced.

Increased insulin secretion is thought to contribute to the progression of diabetes by leading to insulin resistance (decreased insulin sensitivity) and exhaustion of pancreatic β cells (insulin secreting cells). In addition, many epidemiological studies have revealed that postprandial hyperglycemia increases the risk of vascular diseases that are complications of diabetes (Non-patent Document 12).
The product of the present invention reduces insulin secretion without worsening blood glucose after meals, and is considered to be effective in preventing and improving diabetes.

Comparative Example 1 Effect of β-chitin non-nanofiber on blood insulin and blood GIP Inhibition of increase in GIP and insulin when β-chitin non-nanofiber is provided as a blood GIP and / or blood insulin increase inhibitor The effect was tested.

1-1 Comparative Test Sample The β-chitin non-nanofibers of Comparative Production Example 1 and Comparative Production Example 2 were used.

1-2 Test animals
Eight-week-old male mice C57BL / 6J Jcl (Clea Japan) were used. Each group was N = 4.

1-3 Preparation and Dosage of Administration Sample A gastric administration sample of β-chitin non-nanofiber was prepared in exactly the same manner as the preparation method shown in Example 1. The dose to animals was the same as in Example 1 1-3 (Table 1), and the amount was obtained by replacing β-chitin nanofibers with β-chitin non-nanofibers.

1-4 Stomach administration test (blood insulin, blood GIP measurement)
In the same manner as the intragastric administration test method shown in 1-4 of Example 1, a comparative test sample was administered to animals, and blood insulin and blood GIP measurements were measured.

表４、表５の結果から、比較例１のβ-キチン非ナノファイバー投与群の食後の最大ＧＩＰ値（Δ10分値）及び最大インスリン値（Δ10分値）は、コントロール投与群と差がなかった。この結果から、β-キチン非ナノファイバーには、血中ＧＩＰ低減、血中インスリン上昇抑制効果はなく、本発明品のβ-キチンナノファイバーにのみ得られる効果であると考えられた。 1-5 Results The results were tabulated and statistically analyzed by the same method as shown in 1-5 of Example 1.

From the results of Tables 4 and 5, the maximum post-meal GIP value (Δ10 min value) and the maximum insulin value (Δ10 min value) of the β-chitin non-nanofiber administration group of Comparative Example 1 are not different from the control administration group. It was. From these results, it was considered that β-chitin non-nanofibers had no effect on blood GIP reduction and blood insulin elevation suppression, and were obtained only by the β-chitin nanofibers of the present invention.

Claims (8)

  An oral administration agent containing β-chitin nanofibers.   A blood GIP (Gastric inhibitory polypeptide) elevation inhibitor containing β-chitin nanofibers.   A blood insulin elevation inhibitor comprising β-chitin nanofibers.   Diabetes preventive / ameliorating agent containing β-chitin nanofibers.   The oral administration agent according to claim 1, wherein the β-chitin nanofibers have an average fiber width of 100 nm or less.   The blood GIP inhibitor according to claim 2, wherein the β-chitin nanofibers have an average fiber width of 100 nm or less.   The blood insulin elevation inhibitor according to claim 3, wherein the β-chitin nanofibers have an average fiber width of 100 nm or less.   The agent for preventing or improving diabetes according to claim 4, wherein the β-chitin nanofibers have an average fiber width of 100 nm or less.

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