JP2005053863A - Prophylactic and therapeutic agent for diabetes mellitus disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a prophylactic and therapeutic agent for diabetes mellitus disease and a functional food or food material for prophylaxis/improvement of diabetes mellitus disease, capable of effectively utilizing Alpinia specios K. Schum in which utilization of excellent physiological activity is not sufficiently carried out, being readily available as an ingredient derived from the plant, scarcely having adverse effect on living bodies and having high safety. <P>SOLUTION: This prophylactic and therapeutic agent for the diabetes mellitus disease comprises a fermentation treated substance obtained by fermenting Alpinia specios K. Schum with lactic acid bacterium, lactic acid bacterium and Bacillus subtilis or lactic acid bacterium, yeast and Bacillus subtilis as an active ingredient, and the fermentation treated substance is the substance obtained by carrying out fermentation treatment of its leaf with a mixed bacterium of Lactobacillus plantarum with Streptococcus thermophilus and Bacillus subtilis. The prophylactic and therapeutic agent for diabetes mellitus disease has an action lowering contents of glucose, insulin and total cholesterol and nitrogen monoxide in serum and lowering blood glucose level and lowering renal LPO. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a diabetic disease preventive / therapeutic agent using a physiologically active substance derived from a ghetto plant growing in Okinawa, and a functional food or food material for the prevention / amelioration of diabetic disease.

  Conventionally, excellent natural resources containing active ingredients such as antioxidant activity have been developed for plants growing in Okinawa. For example, processed foods (for example, refer to Patent Document 1) in which medicinal turmeric rhizomes are applied to improve the taste, and antioxidant plant fibers using plant fibers that are not used as foodstuffs and their processing Foods (for example, refer to Patent Document 2), processed foods (for example, refer to Patent Document 3) that use guava leaves, moon peaches, mugwort, tea leaves, etc. to improve the medicinal effect by fermentation treatment and improve the taste. Has been developed. Further, a substance for inhibiting α-amylase activity, characterized by comprising as an active ingredient a dry powder or extract of one or more kinds of plants selected from the group consisting of ghetto, red-crowned wrinkles, hiraemon lemon, damselfly and strelitzia (For example, refer patent document 4) etc. are also reported.

The ghetto (Alpinia Speciosa K. Schum) belongs to the family Gingidae (Zingiberaceae), also known as Alpinia. It is distributed from southern Kyushu to southern China to tropical Asia. Although it is used as a raw material for ropes, it is not used enough for food.
Japanese Patent Application Laid-Open No. 11-289973 JP 2002-204673 A JP 2002-330725 A JP 2001-333733 A

  An object of the present invention is to find an excellent physiologically active substance contained in a plant, to make effective use of the plant, to easily obtain it as a plant-derived component, and to provide an anti-diabetic agent with low side effects on the living body and high safety. It is to provide.

  The present inventors reduce the content of glucose, insulin, total cholesterol, and nitric oxide in serum by applying a specific fermentation treatment for ghettos that grow naturally in Okinawa, particularly leaves, and lower blood glucose levels. The present inventors have found that there is an action of lowering renal LPO and have completed the present invention.

  That is, the present invention provides a prophylactic / therapeutic agent for diabetic diseases characterized in that ghetto is a fermented product obtained by fermenting ghetto with lactic acid bacteria, lactic acid bacteria and yeast, lactic acid bacteria and Bacillus subtilis, or lactic acid bacteria, yeast and Bacillus subtilis. Preferably, the fermented processed product is a fermented processed product of ghetto leaves, and the preventive / therapeutic agent for diabetic diseases according to claim 1 (claim 2) or the lactic acid bacterium is Streptococcus. , Belonging to any one of the genus Lactobacillus, Leuconostoc, Pediococcus, Bifidobacterium or Tetragenococcus Item 3. The agent for preventing or treating diabetes disease according to item 1 or 2 (claim 3) or a bacterium belonging to the genus Streptococcus is Streptococcus. The antidiabetic disease preventive / therapeutic agent according to claim 3 (Claim 4) or a bacterium belonging to the genus Lactobacillus, which is S. thermophilus, or Lactobacillus plantarim (L. plantarum), Lactobacillus delbruckii (L. delbruckii), Lactobacillus pentosus (L. pentosus) or Lactobacillus casei (L. casei) (Claim 5), or the microorganism belonging to the genus Tetragenococcus is T. halophilus, or the fermented product (Claim 6) or yeast according to claim 3, wherein the yeast is Candida. The preventive / therapeutic agent for diabetic diseases according to claim 1 (Claim 7) or the genus Candida, which belongs to the genus Candida or Saccharomyces The antibacterial agent for preventing or treating diabetes (Claim 8) or the bacterium belonging to the genus Saccharomyces, wherein the bacterium belonging to C. versatilis, or the genus Saccharomyces is Saccharomyces cerevisiae (S. The antidiabetic disease preventive / therapeutic agent according to claim 7 (Claim 9) or Bacillus subtilis (B. subtilis) according to Claim 7, characterized in that it is cerevisiae). The preventive / therapeutic agent for diabetes disease according to claim 10 (claim 10), or a fermented product of a mixed bacterium of Lactobacillus plantarim, Streptococcus thermophilus, or Bacillus subtilis, according to claim 1. It has a therapeutic agent (Claim 11) or a glucose content-reducing action in serum. A disease preventive / therapeutic agent (Claim 12), or a diabetes preventive / therapeutic agent (Claim 13) according to any one of claims 1 to 12, which has an action of reducing the insulin content in serum. The agent for reducing or treating diabetes mellitus according to any one of claims 1 to 13, which has an action of reducing the total cholesterol content in serum (claim 14), and the nitric oxide content in serum The agent for preventing or treating diabetes mellitus according to any one of claims 1 to 14, which has a reducing action (claim 15), or the action of reducing the content of renal LPO. The preventive / therapeutic agent for diabetic disease according to any one of claims 15 (Claim 16) or the preventive / therapeutic agent for diabetes disease according to any one of Claims 1-16 (Claim 16) 17).

  In addition, the present invention provides a functional food or food material for the prevention / amelioration of diabetic diseases, characterized by comprising the agent for preventing / treating diabetic diseases according to any one of claims 1 to 17 as an active ingredient (claim 18). )

  The anti-diabetic disease preventive / therapeutic agent of the present invention has been found to have excellent physiological activity, and can be effectively used as a plant-derived component for effective utilization of an excellent physiologically active substance in ghetto that has not been sufficiently used for food. It is intended to provide a prophylactic / therapeutic agent for diabetic diseases and a functional food or food material for preventing / ameliorating diabetic diseases, which can be obtained easily and has low side effects on the living body and high safety.

  The preventive / therapeutic agent for diabetic diseases of the present invention is an agent that contains a fermented product obtained by fermenting ghetto with lactic acid bacteria, lactic acid bacteria and yeast, lactic acid bacteria and Bacillus subtilis, or lactic acid bacteria and yeast and Bacillus subtilis as active ingredients. However, it is not particularly limited, and the use part of the ghetto may be an underground part such as a root or a rhizome, or an above-ground part such as a stem, a leaf, a flower or a fruit, and these two or more kinds may be used. Although a mixture may be sufficient, the fermented processed material of a leaf is especially preferable.

  The fermented ghetto used in the preventive / therapeutic agent for diabetic diseases of the present invention is obtained by fermenting ghetto, and examples of microorganisms used for the fermenting treatment include lactic acid bacteria, yeasts, and Bacillus subtilis. More specifically, lactic acid bacteria are preferably used, and examples include lactic acid bacteria alone, lactic acid bacteria and yeast, lactic acid bacteria and Bacillus subtilis, or a combination of lactic acid bacteria and yeast and Bacillus subtilis.

Examples of the lactic acid bacteria used for the fermenting treatment of the ghetto include Streptococcus, Lactobacillus, Leuconostoc, Pediococcus, Bifidobacterium, and Tetracoccus. Bacteria belonging to any of the genus Tetragenococcus are preferable, and the genus Lactobacillus is particularly preferable. The bacterium belonging to the genus Streptococcus is preferably Streptococcus thermophilus (S. thermophilus), and specific examples include Streptococcus thermophilus IFO13957 strain. Moreover, as a bacterium belonging to the genus Lactobacillus, any of Lactobacillus plantarim (L. plantrum), Lactobacillus delbruckii (L. delbruckii), Lactobacillus pentosus (L. pentosus) or Lactobacillus casei (L. casei) Among these bacteria, Lactobacillus plantarim is particularly preferable. Specific examples of such Lactobacillus plantarim include IFO14712 and IFO14713 strains, Lactobacillus delbriqui as IFO13953 strain, Lactobacillus pentosus as IFO12011 strain, and Lactobacillus casei as IFO15883 strain. Moreover, as a microbe which belongs to Tetragenococcus genus, it is preferable that it is Tetrageno halophyllus (T. halophilus), and tetrageno halophyllus IFO12172 strain can be illustrated concretely. These lactic acid bacteria, dry basis 1g leaf Alpinia zerumbet, usually 10 ³ to 10 ^7, it is preferable to use particularly 10 ⁶ to 10 ^7.

Yeast used in the fermenting treatment of ghetto is added mainly for the improvement of fragrance, and as such yeast, bacteria belonging to the genus Candida or Saccharomyces are preferable. As such a bacterium belonging to the genus Candida, Candida versatilis is preferable, and IFO10038 strain can be specifically exemplified as Candida versatilis. The bacterium belonging to the genus Saccharomyces is preferably S. cerevisiae, and IFO0555 strain can be specifically exemplified as Saccharomyces cerevisiae. It is preferable to use 10 ³ to 10 ⁷ , especially 10 ⁶ to 10 ⁷ , of these yeasts per 1 g of dry matter of Momotamana leaves.

Further, Bacillus subtilis IFO3013 strain can be specifically exemplified as the Bacillus subtilis used in the fermentation treatment of ghetto. These B. subtilis, dry basis 1g leaf Alpinia zerumbet, usually 10 ³ to 10 ^7, it is preferable to use particularly 10 ⁶ to 10 ^7.

  In such a ghetto fermentation process, the group of microorganisms preferably used is preferably a group of microorganisms including lactic acid bacteria, yeast and Bacillus subtilis. It is preferable to use the same number as the number of bacteria for the dry matter of ghetto leaves. By using the bacteria in such a combination of the number of bacteria, the fermentation time can be shortened, and thus the propagation of various bacteria can be suppressed.

In the fermented ghetto, the dried ghetto leaf is pulverized to a particle size of 3 mm or less, preferably 0.5 to 1.0 mm. By setting the particle size to 3 mm or less, a sufficient contact area with the fermenting bacteria can be secured, fermentation can proceed effectively, and the particle size in the range of 0.5 to 1.0 mm. This effect can be obtained more remarkably. In order to promote the progress of fermentation, it is preferable to add 1 to 10 parts by weight, particularly about 4 to 6 parts by weight, of water to 1 part by weight of dry matter. To the pulverized plant, the above-mentioned fungus or fungus group is added. It is preferable to add 1 to 10% by weight of each fungus group after culturing each fungus before mixing to the medium and adding to the medium in advance. Fermentation is preferably performed at a temperature of 20 to 50 ° C., preferably 40 ° C., and the fermentation time can be appropriately selected depending on the progress of fermentation under conditions such as pH and the number of bacteria, and preference. If the pH is 4 to 5 and the number of bacteria is 10 ⁶ or more, it is preferably about 72 hours. At the time of fermentation treatment, aeration or deoxygenation treatment can be performed as necessary, but fermentation can be performed in static culture after the deoxygenation treatment. The fermentation format is preferably solid culture rather than liquid culture.

  In such a fermentation treatment, carbohydrates and proteins can be added as an agent for fermenting bacteria. The carbohydrate as the assimilating agent is preferably a commercially available sugar such as glucose, sucrose, molasses, etc., and the amount of these added is preferably 1 to 10% by weight per medium, particularly around 3% by weight. The protein as an assimilating agent is preferably rice bran, bran or the like, and the addition amount thereof is preferably 1 to 5% by weight per medium. These assimilating agents may be used alone or in combination of two or more.

  After completion of fermentation, drying is preferably performed by a dryer so that the moisture value is 10% by weight or less. As a drying method, heat drying or freeze drying can be used. In the case of heat drying, the product temperature is 100 ° C. It is preferable that the following is performed because the deactivation of the physiologically active ingredient can be prevented. After drying, if necessary, sterilization is performed by a known method such as heating to obtain a fermented processed product of ghetto used as a diabetic disease preventive / therapeutic agent or a raw material of food or food material.

  Such fermented processed ghetto can be used as it is as an active ingredient of the preventive / therapeutic agent for diabetic diseases of the present invention, but can also be subjected to other treatments such as extraction treatment. Examples of the solvent used for such extraction treatment include lower monohydric alcohols such as water, methyl alcohol, and ethyl alcohol, liquid polyhydric alcohols such as glycerin, propylene glycol, and 1,3-butylene glycol, and nonpolar substances such as hexane. One type or two or more types of solvents can be mentioned. As a preferable extraction method, for example, methyl alcohol having a water concentration of 0 to 100% by volume, ethyl alcohol or the like is used, and extraction is performed at 0 to 80 ° C. for 30 minutes to 5 days, etc., preferably using an ethyl alcohol aqueous solution at room temperature for 24 hours. And then filtering. Furthermore, the lyophilized product obtained by lyophilization after removing the solvent of the obtained extracted product can be used advantageously, and if necessary, these extracts can be mixed with a solvent to form a mixture. Can also be used.

  The preventive / therapeutic agent for diabetic diseases of the present invention comprising the fermented ghetto product as an active ingredient has an action of reducing the glucose, insulin, total cholesterol, and nitric oxide content in serum, and has a renal LPO content. It has a reducing action, has a blood sugar level reducing action, and has an α-amylase inhibitory activity.

  The preventive / therapeutic agent for diabetic diseases of the present invention includes the above-mentioned fermented processed ghetto, binder, stabilizer, excipient, diluent, pH buffer, disintegrant, solubilizer, solubilizer, etc. In addition to the addition of various compounding ingredients such as tonics, it can also be used in combination with other therapeutic agents for diabetic diseases such as diabetic hyperglycemia, diabetic hyperlipidemia and diabetic osteoporosis.

  As a method for preparing the preventive / therapeutic agent for diabetic diseases of the present invention, the fermented processed product of the above ghetto is used as it is, or the freeze-dried product of the fermented product extracted with water or ethanol solution is powdered with a mixer or the like. Specific examples include a method of preparing a solution by granulating, encapsulating, tableting, or dissolving, suspending, or dispersing the obtained powder in a conventional manner.

  In the present invention, the diabetic disease refers to diseases that exhibit symptoms of diseases such as type II diabetes and various complications caused by type II diabetes, and examples of diabetic diseases include diabetic osteoporosis, diabetic hyperglycemia, Specific conditions such as diabetic hyperlipidemia, symptoms of weight loss due to diabetes, symptoms of fluctuations in blood mineral concentration due to diabetes, and complications such as neuropathy, retinopathy and kidney disorders It can be illustrated. The prophylactic / therapeutic agent for diabetic diseases of the present invention has an effect of preventing / ameliorating diabetic diseases such as diabetic osteoporosis, diabetic hyperglycemia, diabetic hyperlipidemia, etc. Functional foods and pharmacological compositions having a preventive / ameliorating action for diabetic diseases by adding or blending them into foods for prevention / treatment methods of diabetic diseases by oral administration to reserve personnel It can be advantageously used as a food material. Such a prophylactic / therapeutic agent for diabetic diseases of the present invention is usually administered orally, and when used as a therapeutic agent, it is 1 mg to 5 g / Kg body weight, preferably 10 to 1000 mg / Kg body weight per day as a ghetto fermented product. By taking in a range, diabetic diseases can be improved, but the intake can be appropriately adjusted according to symptoms, sex, age and the like. Moreover, when using as a preventive agent of diabetic disease of this invention, the prevalence of diabetic disease can be reduced by ingesting in advance. The ingestion method as a prophylactic agent can be the same as that used as a therapeutic agent, and the intake can be made from the same amount to a smaller amount than the therapeutic agent.

  The functional food or food material for the prevention and improvement of diabetic diseases of the present invention containing a fermented ghetto product as an active ingredient is used as a part of a raw material for food and drink, or a manufacturing process or It can be obtained by adding and blending after production. Such functional food is not particularly limited, and baked confectionery such as cookies, bread, cakes, rice crackers, tablet confectionery such as ramune confectionery, Japanese confectionery such as mutton, frozen confectionery such as pudding, jelly, ice cream, Sweets such as chewing gum and candy, snacks such as crackers and chips, noodles such as udon and buckwheat, fish paste products such as kamaboko, ham, and fish sausage Seasonings such as dressing, mayonnaise, sweeteners, tofu, konnyaku, other boiled dishes, dumplings, croquettes, salads, soups, stews, etc. Specific examples include various drinks such as black tea, sencha, oolong tea, and sports drinks. For example, a confectionery can be produced by finely pulverizing the fermented ghetto product and then tableting the fine powder according to a conventional method. In this case, the fine powder can be granulated and then tableted. . Moreover, the fermented processed product of ghetto can be made into a fine powder, and a mixture of lactose, dextrin, dry yeast and the like can be tableted.

  EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, the technical scope of this invention is not limited to these illustrations.

[Preparation of sample] Production of fermented processed product 30 g of dried ghetto leaves were pulverized to a particle size of 0.1 to 3 mm and placed in a container. 30 g of water and 0.9 g of molasses were added to a container containing ghetto. After culturing each of the bacteria of Lactobacillus plantarim, Streptococcus thermophilus, and Bacillus subtilis in a container containing the crushed ghetto, the bacteria were mixed at a ratio of 1: 1: 1. Weight% was added, the container was sealed, and fermentation was performed by static culture. The fermentation temperature was 40 ° C. and the fermentation time was 72 hours. Then, after drying at 60 degreeC until the moisture value became 10 weight% or less with a dryer, the sterilization process (130 degreeC steam, 5-15 seconds) was performed, and 30 g of fermented ghettos were obtained. Then, add water so that it becomes a ratio of 10 ml per 1 g of dried fermented ghetto leaves, extract with hot water at 80 ° C. for 20 minutes, pool the supernatant, and make a ratio of 10 ml per 1 g of precipitate. Water was added again, followed by hot water extraction at 80 ° C. for 20 minutes, and freeze-dried as a hot water extract together with the supernatant. Hereinafter, a hot water extraction freeze-dried product of the ghetto was used as a sample.

  As a comparative example, dried unfermented ghetto leaves were pulverized with a miller for 1 minute, water was added to a ratio of 10 ml to 1 g of pulverized leaves, and the unfermented extract was prepared in the same manner as the sample. Prepared.

[Method of administration]
KK-Ay diabetic male model mouse (4 weeks old) improved as a type 2 diabetes model in which obesity gene Ay is introduced into KK mice and early (7-8 weeks old) and severely expresses obesity and hyperglycemia than KK mice ) (Obtained from CLEA Japan). The grouping is
1) Control group (C) (10 mice) administered with 5 ml / kg of distilled water
2) Group (10 mice) administered with fermented ghetto extract (sample) 250 mg / 5 ml · kg
3) Group (9 animals) administered with 250 mg / 5 ml · kg of unfermented ghetto extract
The administration of the sample was started from 7 weeks of age, and was orally administered with the day of the week determined 3 times / week and the administration time from 17 to 18 o'clock.

[Measure blood glucose level]
A sample is administered and fasted 16 to 19 hours after administration of the sample, the tip of the mouse's tail is injured with a razor to collect blood, and a simple blood glucose self-monitoring device Novo Assist (manufactured by Novoldisk Pharma) It was measured by. Thereafter, blood was collected at a rate of once every two weeks, and the blood glucose level was measured. From the blood glucose measurement value, the ratio of the blood glucose level to the control group of the sample administration group was determined from the blood glucose measurement value, and the results are shown in Table 1. Similarly, the ratio of blood glucose level relative to the control group was determined for the unfermented ghetto extract administration group, and the results are shown in Table 1.

表１に示される結果から、サンプル投与群の血糖値は、サンプル投与開始直後は未発酵ゲットウ抽出物投与群の血糖値より僅かに高いものの、サンプル投与を継続すると、サンプル群において１２週目あたりから未発酵ゲットウ抽出物投与群に比較して、血糖値が顕著に低減していくことがわかった。

From the results shown in Table 1, the blood glucose level of the sample administration group was slightly higher than the blood glucose level of the unfermented ghetto extract administration group immediately after the start of sample administration. From the results, it was found that the blood glucose level was significantly reduced as compared with the unfermented ghetto extract administration group.

[Blood collection]
A 17-week-old mouse administered with the sample on the previous day was killed by decapitation after fasting for 4 hours the next morning, and blood was collected from the decapitation incision into a test tube. Thereafter, the abdomen was incised, the kidney and liver were removed, weighed, wrapped in foil, and stored at −80 ° C. without perfusion. The blood was 3000 r. p. The serum was separated into Eppendorf by centrifugation once at m15 minutes, and further centrifuged under the same conditions to separate the serum into the same Eppendorf. This eppendorf was cooled and centrifuged (4 ° C., 3000 rpm, 2 minutes), dispensed into another eppendorf and a test tube (for serum Glu), and the eppendorf was stored at −80 ° C.

[Measurement of serum glucose]
The glucose content of the serum obtained in Example 4 was measured using Glucose CII / Test Wako (Mutarose / GOD method) (manufactured by Wako). The results are shown in FIG. From the results shown in FIG. 2, it was revealed that the glucose content in serum was reduced in the sample administration group.

[Measurement of serum insulin]
The serum obtained in Example 4 was stored at −80 ° C., dissolved and used for measurement of serum insulin. For the measurement of serum insulin, an insulin measurement kit (manufactured by Morinaga Bioscience Laboratories) was used, which used a microplate ELA sandwich method and was measured with a microplate reader. The results are shown in FIG. From the results shown in FIG. 3, it is clear that serum insulin is significantly reduced in the sample administration group, and that the insulin content in serum is significantly reduced even when compared with the unfermented extract administration group. It was. The remaining serum was stored frozen at -20 ° C.

[Measurement of serum nitric oxide]
Serum that had been stored frozen at −20 ° C. (see Example 6) was dissolved and used to measure serum nitric oxide. The measurement of nitric oxide was performed using a NO analyzer (ENO-20 nitric oxide analyzer: manufactured by Acom). As a sample pretreatment, 100 μl of serum and 100 μl of methanol are placed in an Eppendorf, mixed well, allowed to stand for 20 minutes, cooled and centrifuged (4 ° C., 13,000 rpm, 10 minutes), and 100 μl of the supernatant is sampled. The sample was dispensed into a tube, and nitric oxide was measured with a NO analyzer. All operations up to pretreatment were performed in ice. The results are shown in FIG. From the results shown in FIG. 4, it became clear that the serum nitric oxide content was reduced in the momotana group.

[Measurement of serum total cholesterol]
The serum dissolved in Example 7 was stored overnight refrigerated (4 ° C.). 10 μl of serum was operated in half with the reagent, and total cholesterol was measured using Cholesterol C-Test Wako (cholesterol oxidase / pheninol method) (manufactured by Wako). The results are shown in FIG. From the results shown in FIG. 5, it was revealed that the total cholesterol content of serum was significantly reduced in both the sample administration group and the unfermented extract administration group.

[Kidney LPO]
The kidney obtained in Example 4 was stored at −80 ° C. and then subjected to ultrasonic homogenizer treatment using a 1.15% KCl aqueous solution at a rate of 5 ml / g. After the kidney was crushed to some extent by this ultrasonic homogenizer treatment, it was centrifuged for 30 seconds (10,000 rpm in ice). The obtained supernatant was further diluted 2-fold with the above KCl aqueous solution, and LPO of kidney homogenate was measured by the TBA method. The results are shown in FIG. From the results shown in FIG. 6, it was revealed that renal LPO was reduced in the sample administration group.

[Α-amylase inhibitory activity]
In the process of Example 1, 10 ml of 50% ethanol aqueous solution was added to 1 g of fermented ghetto obtained by sterilization after fermentation of ghetto leaves, followed by extraction at room temperature for 12 hours and filtration. 10 ml of 50% ethanol aqueous solution was added to the residue again, followed by extraction at room temperature for 12 hours, followed by filtration to obtain a sample solution as a 50% ethanol extract. After mixing 0.5 ml of the obtained sample solution with 1 ml of 4% starch solution (manufactured by WAKO) and 1.5 ml of phosphate buffer, the mixture was heated at 37 ° C. for 5 minutes, and then 5.5 unit / ml α-amylase solution. 0.02 ml (manufactured by SIGMA) was added and reacted at 37 ° C. for 120 minutes. Thereafter, the reaction was stopped by heating for 10 minutes in boiling water, and the amount of maltose produced was measured by high performance liquid chromatography (manufactured by Shimadzu Corporation). The maltose production amount in the case of control (no sample added) is 100%, and the ratio of the maltose production amount at the time of sample addition, that is, α-amylase activity is shown in FIG. From the results shown in FIG. 7, in the sample administration group, α-amylase activity is reduced, α-amylase inhibitory activity is remarkable, and it is significant even compared with the unfermented ghetto extract administration group. Was revealed.

It is a figure which shows the blood glucose level which applied the antidiabetic disease prophylactic / therapeutic agent of this invention to the KK-Ay diabetic male model mouse. It is a figure which shows the glucose content in the serum which applied the antidiabetic disease preventive / therapeutic agent of this invention to the KK-Ay diabetic male model mouse. It is a figure which shows the insulin content in the serum which applied the antidiabetic disease prophylactic / therapeutic agent of this invention to the KK-Ay diabetic male model mouse. It is a figure which shows the nitric oxide content in the serum which applied the antidiabetic disease preventive / therapeutic agent of this invention to the KK-Ay diabetic male model mouse. It is a figure which shows the cholesterol content in the serum which applied the antidiabetic disease prophylactic / therapeutic agent of this invention to the KK-Ay diabetic male model mouse. It is a figure which shows renal LPO content which applied the antidiabetic disease preventive / therapeutic agent of this invention to the KK-Ay diabetic male model mouse. It is a figure which shows the alpha-amylase inhibitory activity of the antidiabetic disease preventive / therapeutic agent of this invention.

Claims (18)

A preventive / therapeutic agent for diabetic diseases, characterized by comprising a fermented product obtained by fermenting ghetto with lactic acid bacteria, lactic acid bacteria and yeast, lactic acid bacteria and Bacillus subtilis, or lactic acid bacteria and yeast and Bacillus subtilis. The preventive / therapeutic agent for diabetic diseases according to claim 1, wherein the fermented product is a fermented product of ghetto leaves. Lactic acid bacteria are any of the genus Streptococcus (Storeptococcus), Lactobacillus, Leuconostoc, Pediococcus, Bifidobacterium or Tetragenococcus The preventive / therapeutic agent for diabetic diseases according to claim 1 or 2, wherein 4. The preventive / therapeutic agent for diabetic diseases according to claim 3, wherein the bacterium belonging to the genus Streptococcus is Streptococcus thermophilus. The bacterium belonging to the genus Lactobacillus belongs to any one of L. plantarum, L. delbruckii, L. pentosus or L. casei The preventive / therapeutic agent for diabetic diseases according to claim 3. 4. The fermented product according to claim 3, wherein the bacterium belonging to the genus Tetragenococcus is T. halophilus. The agent for preventing or treating diabetes mellitus according to claim 1, wherein the yeast belongs to the genus Candida or Saccharomyces. 8. The preventive / therapeutic agent for diabetic disease according to claim 7, wherein the bacterium belonging to the genus Candida is C. versatilis. 8. The preventive / therapeutic agent for diabetic diseases according to claim 7, wherein the bacterium belonging to the genus Saccharomyces is S. cerevisiae. 2. The preventive / therapeutic agent for diabetic diseases according to claim 1, wherein the Bacillus subtilis is B. subtilis. 2. The preventive / therapeutic agent for diabetic diseases according to claim 1, which is a fermented product of a mixed bacterium of Lactobacillus plantarim, Streptococcus thermophilus, and Bacillus subtilis. The agent for preventing or treating diabetes mellitus according to any one of claims 1 to 11, which has an action of reducing the glucose content in serum. The agent for preventing or treating diabetic disease according to any one of claims 1 to 12, which has an action of reducing the insulin content in serum. The prophylactic / therapeutic agent for diabetic diseases according to any one of claims 1 to 13, which has an action of reducing the total cholesterol content in serum. The diabetic disease preventive / therapeutic agent according to any one of claims 1 to 14, which has an action of reducing the content of nitric oxide in serum. The prophylactic / therapeutic agent for diabetic diseases according to any one of claims 1 to 15, which has an action of reducing the content of renal LPO. The agent for preventing or treating diabetic disease according to any one of claims 1 to 16, which has a blood glucose level reducing action. A functional food or food material for the prevention / amelioration of diabetic disease, comprising the diabetic disease preventing / treating agent according to claim 1 as an active ingredient.

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