Composition for improving blood sugar level and / or intestinal environment

Abstract

To provide a blood glucose level and / or intestinal environment improving composition, etc. which are simply ingestible.SOLUTION: A blood glucose level and / or intestinal environment improving composition comprises limonite. A dose of limonite is preferably 50 mg / day to 2000 mg / day. There is also provided a health food in the shape of powder, a tablet, or a capsule which contains the blood glucose level and / or intestinal environment improving composition.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present invention relates to a composition for improving blood sugar levels and / or the intestinal environment. [Background technology]

[0002] Limonite is an iron oxide mineral that contains various minerals such as calcium and magnesium in addition to iron, and is therefore used as a livestock feed additive and a health supplement for pets. Limonite also has the ability to absorb odors, and is used to reduce body odor and feces odors (Patent Documents 1 and 2). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2006-051022 [Patent Document 2] WO2018-190133 publication Summary of the Invention [Problem to be solved by the invention]

[0004] However, the relationship between limonite and blood sugar levels or the intestinal environment in humans was unknown. The present invention has been made in consideration of the above-mentioned circumstances, and its purpose is to provide a composition for improving blood sugar levels and / or the intestinal environment that is easy to ingest and has a sufficient effect on improving blood sugar levels. [Means for solving the problem]

[0005] To achieve the above object, the present invention provides a composition for improving blood sugar levels and / or intestinal environment, characterized by containing limonite. Limonite, also known as limonite or bog iron ore, is an iron oxide mineral. Limonite is the yellow soil that precipitates when iron-rich water in swamps or shallow seas comes into contact with air. In Japan, it is collected, for example, around Mount Aso. The iron oxide contained in limonite has a strong binding capacity for gases and harmful substances, and this adsorption ability is utilized for its use as an activated soil for soil improvement and a water purification agent. It is also used as a livestock feed additive (e.g., Light Minerals®) and a pet health supplement (e.g., Demiel®) to provide multi-mineral intake. Limonite is an aggregate of either or both goethite (goethite, α-FeOOH) and lepidocrocite (γ-FeOOH) containing adsorbed and / or capillary water. Although the crystal structure of goethite differs from that of lepidocrocite, the occurrence and paragenesis of the two are similar, and they occur together. Since it is difficult to distinguish between the two, especially in the case of aggregates of microscopic crystals, and it is often not necessary to strictly distinguish between the two, the term limonite is used in such cases. The limonite used in the present invention can be taken as a health food or mixed with food and drink, either directly after collection or crushed to an appropriate size after aging for 5 years or less, or after being appropriately refined. However, limonite aged for 5 years or more after collection can also be used.

[0006] Diabetes is mainly divided into type 1 diabetes and type 2 diabetes. Type 1 diabetes is a disease in which destruction of beta cells in the islets of Langerhans in the pancreas causes insulin depletion, leading to hyperglycemia and diabetes. Type 2 diabetes is a disease in which obesity and other factors reduce insulin secretion from beta cells, reducing the ability of muscle and adipose tissue to take up glucose. As a result, blood glucose is not stored as glycogen in the liver or adipose tissue, causing blood glucose levels to exceed the normal range and resulting in diabetes. The present invention is expected to improve diabetes or borderline diabetes by improving abnormal blood glucose levels. In the present invention, the dosage of limonite is preferably 5 mg / day to 2000 mg / day (preferably 100 mg / day to 1000 mg / day, more preferably 200 mg / day to 600 mg / day, and even more preferably 200 mg / day to 400 mg / day). Furthermore, it is known that limonite is non-toxic when orally administered to rats at 4g / kg / day for 13 weeks, making it a very safe substance. However, oral administration can be difficult if the intake amount is too large (for example, giving 4g / kg per day to a 60kg person would amount to 240g). Furthermore, the inventors have confirmed that administration of 300mg / day improves blood glucose levels. Based on these data, a dose in the range of 200mg / day to 1000mg / day (preferably 200mg / day to 600mg / day) is easy to ingest and provides sufficient effects.

[0007] In the present invention, from the viewpoint of texture and taste, the health food is preferably in the form of a powder, tablet, or capsule. When limonite is orally ingested as a health food, it is easiest to make it into a tablet or capsule form, and therefore such a form is preferred. When used as a health food, it can be distributed in its original form, or in a form containing an excipient. A limonite-containing composition containing limonite and an excipient is a preferred embodiment, as it further improves the stability of the limonite and makes it easier to drink. Examples of such excipients include lactose, starch, cyclodextrin, galactomannan, dextrin, and maltodextrin. The content of the excipient is not particularly limited, but is preferably 5 parts by mass or more (50 parts by mass or more, or 100 parts by mass or more) per 100 parts by mass of limonite.

[0008] The blood glucose level and / or intestinal environment improving composition of the present invention can be incorporated into various foods and beverages. For example, it may be a beverage such as a soft drink, carbonated drink, nutritional drink, fruit drink, or lactic acid drink, or a concentrated concentrate or powder of these beverages. The blood glucose level and / or intestinal environment improving composition can be added to frozen desserts such as ice cream, sherbet, and shaved ice, or noodles such as soba, udon, harusame, gyoza (dumpling) wrappers, shumai (steamed dumpling) wrappers, Chinese noodles, and instant noodles. The blood glucose level and / or intestinal environment improving composition can also be added to sweets such as candy, candy, gum, chocolate, tablet candy, gummy candy, snacks, biscuits, jellies, puddings, jams, creams, and baked goods. Furthermore, the composition for improving blood sugar levels and / or intestinal environment can be added to processed seafood and livestock foods such as kamaboko, ham, and sausage, dairy products such as processed milk and fermented milk, oils and fats and oil-based foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings, seasonings such as sauces and other condiments, soups, stews, salads, side dishes, pickles, etc. Furthermore, in powder, tablet, or capsule form, it can be added to various forms of health and nutritional supplements such as jelly drinks and energy drinks, oral fresheners for oral use such as mouth fresheners and breath fresheners, quasi-drugs such as toothpaste and mouthwash, emollient creams, emollient lotions, etc. The amount of limonite to be blended is not particularly limited, but it can be blended in food or drink so as to be, for example, 0.01% by mass to 10% by mass. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide a composition and the like that can be easily ingested and that is sufficiently effective in improving blood sugar levels. [Brief explanation of the drawings]

[0010] [Figure 1] 1 is a graph showing the change in blood glucose level over time from the third week to the eighth week in Efficacy Confirmation Test 1. [Figure 2] 1 is a bar graph comparing blood glucose levels on day 49 between each group. [Figure 3] 1 is a graph showing the time course of blood glucose levels after glucose administration. [Figure 4] 1 is a bar graph showing the blood glucose levels of each group before glucose administration (0), 15, 30, 60, and 120 minutes after administration, as well as a bar graph showing the AUC (area under the graph) of the blood glucose levels of each group. [Figure 5] 1 is a bar graph showing blood insulin concentrations in all four groups 2 minutes after intraperitoneal glucose administration, 8 weeks after STZ administration. [Figure 6] 1 is a bar graph showing the proportion of regulatory T cells (T-reg) in the pancreas (proportion of CD25+ CD4 T cells among CD4 T cells) in all four groups. [Figure 7] FIG. 1 shows the results of analyzing the bacterial flora in the feces of Group 1 (control, no LM), Group 2 (diabetic, no LM), Group 3 (control, with LM), and Group 4 (diabetic, with LM). [Figure 8] 1 is a graph showing data on the genus Bifidobacterium (bifidobacteria), which was found to have a significant difference in the LM-administered group as a result of fecal bacterial flora analysis. [Figure 9] 1 is a graph showing data on fasting blood glucose levels 4 weeks after administration of LM and insulin resistance (HOMA-IR) 6 weeks after administration in Efficacy Confirmation Test 2. [Figure 10] 1 is a graph showing casual blood glucose levels and blood insulin levels 11 weeks after LM administration. [Figure 11] 1 is a graph showing the time course of blood glucose levels when a glucose tolerance test was performed 8 weeks after the start of LM administration. [Figure 12] 10 is a bar graph comparing blood glucose levels 60 minutes after glucose loading in a glucose tolerance test performed 8 weeks after the start of LM administration. [Figure 13] 1 is a graph showing changes in (A) fasting blood glucose level (BS) and (B) HbA1c in human blood in Efficacy Confirmation Test 3. [Figure 14] This is a graph showing the change in subjects whose fasting BS before oral administration was greater than 90. DETAILED DESCRIPTION OF THE INVENTION

[0011] Next, embodiments of the present invention will be described with reference to the drawings. However, the technical scope of the present invention is not limited to these embodiments, and the invention can be embodied in various forms without changing the gist of the invention. <Production of Composition> Limonite (referred to as LM or LIM in the graphs) was obtained from Nippon Limonite Co., Ltd. Mineral or granular limonite was further pulverized into powder, heat-sterilized, and used as a composition for improving blood glucose levels and / or the intestinal environment (hereinafter simply referred to as the "composition").

[0012] <Effectiveness Confirmation Test 1: Streptozotocin (STZ)-induced Diabetes Test> STZ is a naturally occurring organic compound that is particularly toxic to mammalian pancreatic beta cells, and is therefore used as a reagent in animal experiments to create model animals for type 1 diabetes. 1. Test Method Male mice (23 mice, C57BL / 6 strain) aged 8 to 10 weeks were used. All mice were randomly divided into the following four groups. Group 1: Saline (SAL) / normal diet (NF) group (N=4) Group 2: Streptozotocin (STZ) / NF group (N=6) Group 3: SAL / Limonite 5% (LM) group (N=6) Group 4: STZ / LM group (N=7) From the start of the study (week 0) through week 2, groups 1 and 2 were fed a normal diet (NF), and groups 3 and 4 were fed diets containing 5% limonite (LM, LIM). From day 1 to day 5 of week 3, groups 1 and 3 were given SAL, and groups 2 and 4 were given STZ (40 mg / kg) for five consecutive days. The weight of each individual was measured on the first day of weeks 0 to 9, and the blood glucose level of each individual was measured on the first day of weeks 0, 2, 3, 4, 5, 6, 7, and 8. In addition, feces were collected on the first day of weeks 0 and 9. On the first day of the ninth week, an intraperitoneal glucose tolerance test, insulin secretion stimulation test, and dissection were performed. In the intraperitoneal glucose tolerance test, glucose was administered to each group of rats, and blood glucose concentrations were measured before administration (0), and 15, 30, 60, and 120 minutes after administration. In the insulin secretion stimulation test, blood insulin concentrations were measured before administration (0), and 2, 10, and 30 minutes after administration. In addition, the bacterial flora was analyzed by performing 16S rRNA PCR in feces.

[0013] 2. Test Results Figure 1 shows the changes in blood glucose levels from 3 to 8 weeks after STZ administration, and Figure 2 compares the fasting blood glucose levels on day 49. As shown in the figures, in groups 2 and 4, blood glucose levels rose significantly after STZ administration, indicating the pathology of diabetes. At the same time, it was found that blood glucose levels fell significantly in the groups given limonite (LM, LIM) (groups 3 and 4). Figure 3 shows the time course of blood glucose levels during an intraperitoneal glucose tolerance test. Figure 4 shows a graph (bottom right) comparing the blood glucose levels and AUC of each group at 0, 15, 30, 60, and 120 minutes after the intraperitoneal glucose tolerance test. As shown in the figure, administration of STZ significantly increased blood glucose levels after glucose administration. At this time, it was found that blood glucose levels were significantly reduced in the groups given limonite (LM, LIM). Figure 5 shows the blood insulin concentration 2 minutes after glucose administration 8 weeks after STZ administration. As shown in the figure, (1) the STZ-administered group showed a decrease in insulin secretory ability, and (2) when limonite (LM, LIM) was administered to the STZ-administered group, blood insulin concentration significantly increased. Although not shown in the figure, a comparison of microscopic photographs of hematoxylin-stained pancreatic tissue revealed that the destruction of β cells by STZ was suppressed in the limonite (LM, LIM)-administered group. Figure 6 shows the proportion of regulatory T cells (T-reg) in the pancreas (CD4 T cells, CD25 T cells) in each group. +The graph below shows a comparison of the percentage of CD4 T cells in the LM-administered group. It was found that the number of regulatory T cells increased in the LM-administered group. This suggests that the increase in the percentage of regulatory T cells in the limonite (LM, LIM)-administered group suppresses the destruction of beta cells.

[0014] Figure 7 shows the results of an analysis of the fecal bacterial flora in Group 1 (control, no LM), Group 2 (diabetes, no LM), Group 3 (control, with LM), and Group 4 (diabetes, with LM). Figure 8 shows data on the Bifidobacterium genus, which was significantly increased in the LM-administered group. Recent research has suggested that when intestinal bacterial flora becomes abnormal, short-chain fatty acids decrease, disruption of the intestinal epithelial barrier leads to elevated blood LPS (lipopolysaccharide) levels, which in turn leads to microinflammation and insulin resistance, leading to diabetes. Our results suggest that LM improves diabetes by increasing the Bifidobacterium genus. Thus, in STZ-induced diabetic animal models (type 1 diabetes model animals), the LM administration group showed an effect of improving blood glucose levels, indicating that it may also contribute to the improvement of diabetes (type 1 diabetes).

[0015] <Effectiveness Confirmation Test 2: High-fat diet glucose tolerance evaluation test> 1. Test Method A total of 32 mice were randomly divided into the following four groups (N=8 for each group): Group 1: Normal diet (NF) / Normal diet administration (NF) group Group 2: High-fat diet (HFD) / High-fat diet (HFD) group Group 3: HFD / high-fat diet + limonite 0.5% (HFDLM0.5) group Group 4: HFD / high-fat diet with limonite 5% (HFDLM5) group From 6 weeks before the start of the study (-6W) to week 0 (0W), rats were fed either an NF (group 1) or an HFD (groups 2-4). From day 1 of week 0 (0W), body weight and food consumption were measured on the first day of each week. Blood glucose levels were measured at week 0 (0W) and week 4 (4W), and a glucose tolerance test was performed at week 8. In the glucose tolerance test, glucose was administered intraperitoneally to rats in each group, and blood glucose concentrations were measured before administration (0 min) and 15, 30, 60, and 120 min after administration. Animals were dissected at week 14.

[0016] 2. Test Results Figure 9 shows the results of fasting blood glucose levels 4 weeks after LM administration and insulin resistance (HOMA-IR) 6 weeks after LM administration. After 4 weeks of LM administration, the HFDLM0.5 group had significantly lower fasting blood glucose levels than the HFD group. Furthermore, after 6 weeks of LM administration, the HFDLM5 group had significantly lower HOMA-IR than the HFD group. Figure 10 shows the casual blood glucose and blood insulin levels 11 weeks after LM administration. The blood glucose levels were significantly lower in the LM5 group than in the HFD group. The blood insulin levels were significantly lower in the LM0.5 and LM5 groups than in the HFD group. Figure 11 shows the results of a glucose tolerance test 8 weeks after the start of LM administration. In the three HFD-administered groups, blood glucose levels were significantly increased compared to the NF group, indicating diabetic symptoms. At this time, the groups given LM (HFDLM0.5 and HFDLM5) all showed a tendency for blood glucose levels to decrease compared to the HFD group. As shown in Figure 12, a significant difference was observed between HFD and HFD 60 minutes after HFD5 administration. Thus, in a diabetic model animal (type 2 diabetes model animal) induced by a high-fat diet, the LM administration group showed an effect of improving blood glucose levels, which indicates that it may also contribute to the improvement of diabetes (type 2 diabetes).

[0017] <Effectiveness Confirmation Test 3: Effectiveness Confirmation Test on Humans> A total of 21 volunteer subjects, 14 men and 7 women (age range: 24-67 years, mean age: 45.7 years), were used in a human efficacy confirmation study (however, 2 subjects withdrew after 2 months). Each subject took LM (300 mg) orally once daily for 6 months. Blood samples were taken from each subject monthly, and the following blood levels were measured to examine the effects of limonite: AST, ALT, T.Bil, γGTP (the above four items were used to confirm liver function), BUN, Cr (the above two items were used to confirm kidney function), Fe, Ferritin, Hb (the above three items were used to confirm blood iron dynamics), blood glucose levels (BS), and HbA1C (the above two items were used to confirm blood glucose levels). When the time course data for 6 months was examined, no changes were observed in AST, ALT, T.Bil, γGTP, BUN, Cr, Fe, Ferritin and Hb due to the administration of limonite, which means that there is no effect on liver function, kidney function and iron dynamics. Also, as shown in Figure 13, no significant effect was observed on BS and HbA1c. However, when examining subjects whose fasting blood glucose level before oral administration was 90 mg / dl or more, a tendency for blood glucose level to decrease was observed as shown in Figure 14. Furthermore, when we checked the stool odor, we found that it was reduced overall. Thus, administration of LM to humans showed an effect of improving high blood sugar levels, indicating that it may also contribute to the improvement of diabetes.

[0018] <Example of manufacturing health food> A capsule-type health food was produced by filling 100 mg to 450 mg of limonite powder into hard gelatin capsules (manufactured by Capsugel Japan) using a capsule filling machine. <Examples of food and beverage manufacturing> Chocolate with limonite 500 g of "Fancy Chocolate H" (manufactured by Morinaga & Co., Ltd.) was finely chopped and melted in a hot water bath at 50-55°C. 1-5 g of limonite powder was added and mixed. Next, the chocolate was slowly mixed while being placed in a bowl filled with water at approximately 15°C to cool the bottom. Once the chocolate's temperature had dropped to 27-29°C, the bowl was removed from the water, placed in a hot water bath, and heated to 32°C. After stirring well to ensure the chocolate was at a uniform temperature, the mixture was divided into 5 g portions and placed in containers, cooled at 10°C, and solidified to produce a limonite-containing chocolate health food.

[0019] Limonite Jelly 600g of "Cup Jelly Mix" (manufactured by Ina Food Industry Co., Ltd.) was gradually added to approximately 3 liters of boiling water (over 80°C) while stirring until completely dissolved. 10-50g of limonite powder was added and mixed well. While still hot, the mixture was dispensed into aluminum pouches (10mL each), sealed, and then cooled to approximately 10°C to solidify, producing a stick-type gel health food. Limonite-containing tile crackers 800g of wheat flour, 600g of sugar, 10 eggs, and 5-30g of limonite powder were mixed thoroughly and 15g of the mixture was poured onto an iron plate and baked on both sides to produce a health food product in the shape of a tile cracker. As described above, according to this embodiment, it is possible to provide a composition or the like that can be easily ingested and that is sufficiently effective in improving blood sugar levels and the intestinal environment.

Claims

1. A composition for improving blood sugar levels in healthy individuals with fasting blood sugar levels of 90 mg / dl or higher, characterized by containing limonite collected in the vicinity of Mount Aso in a dosage of 200 mg / day to 600 mg / day.

2. A health food for improving blood sugar levels in powder, tablet or capsule form, containing the blood sugar level improving composition according to claim 1, for healthy individuals with fasting blood sugar levels of 90 mg / dl or higher.

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