WO2015152045A1

WO2015152045A1 - Composition inhibiting fatty liver and nephromegaly caused by diabetes and method for producing same

Info

Publication number: WO2015152045A1
Application number: PCT/JP2015/059604
Authority: WO
Inventors: 基二門脇; 真敏久保田; 近藤　堯; 智子川上
Original assignee: 国立大学法人新潟大学; 株式会社ミヤトウ野草研究所
Priority date: 2014-03-29
Filing date: 2015-03-27
Publication date: 2015-10-08
Also published as: TW201932127A; TWI721407B; TW201625281A; JP2015199707A; TWI664970B; KR20170004977A; CN106470692A; CN106470692B; SG10201707707XA; JP6047609B2; SG11201606837XA; KR101873141B1

Abstract

The purpose of the present invention is to propose a composition which comprises earthworm as an active ingredient and can inhibit fatty liver and nephromegaly that are likely induced by diabetes. The composition, which inhibits fatty liver and nephromegaly caused by diabetes, is prepared by: inoculating a fruit and vegetable extract with yeasts to give a fermented liquor; adding earthworms to the fermented liquor and fermenting the earthworms to give fermented earthworms; adding, to the fermented earthworms, Panax notoginseng followed by fermenting and drying to give a fermented mixture; and mixing the fermented mixture with ants and gingko leaves.

Description

Composition for inhibiting fatty liver and renal hypertrophy due to diabetes and method for producing the same

The present invention relates to a composition for suppressing fatty liver and renal hypertrophy due to diabetes and a method for producing the same.

Earthworms have long been used in East Asia as herbal medicines such as antipyretic analgesics, and in recent years, antidiabetic agents (patent document 1) and antihyperlipidemic agents (patent document 1) containing earthworm components as active ingredients. 2) A blood pressure regulator (Patent Document 3) and the like have been proposed.

Japanese Patent Publication No. 07-080778 Japanese Patent Publication No. 07-080777 Japanese Patent Publication No. 07-039349

As described above, earthworms are considered to have various effects, and as a result of researches on further effects of earthworms, the present inventors finally found that the earthworm component is a fat caused by diabetes. It has been found that it has a new effect of suppressing the onset of liver and kidney hypertrophy.

The object of the present invention is to propose a composition that suppresses fatty liver and renal hypertrophy that are likely to be caused by diabetes by containing earthworm as an active ingredient, and a method for producing the same.

The gist of the present invention will be described with reference to the accompanying drawings.

The present invention relates to a composition for suppressing fatty liver and renal hypertrophy due to diabetes, comprising earthworm as an active ingredient.

The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 1, wherein the earthworm is a fermented earthworm fermented with a fermentation broth obtained by inoculating a fruit and vegetable extract with yeast. The present invention relates to a composition that suppresses fatty liver and renal hypertrophy due to diabetes.

The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 1, wherein the earthworm is a worm earthworm. .

The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 2, wherein the earthworm is a worm earthworm. .

The composition for inhibiting fatty liver and renal hypertrophy due to diabetes according to any one of claims 1 to 4, comprising at least one of ginseng, ants, and ginkgo leaves. The present invention relates to a composition that suppresses liver and kidney hypertrophy.

5. The composition for suppressing fatty liver and kidney enlargement due to diabetes according to any one of claims 1 to 4, comprising a ginseng, an ant and a ginkgo leaf. The present invention relates to a composition that suppresses hypertrophy.

The composition for suppressing fatty liver and kidney enlargement due to diabetes according to claim 5, wherein the ant is a fermented fermented ant. It is concerned.

The composition for suppressing fatty liver and kidney enlargement due to diabetes according to claim 6, wherein the ant is a fermented fermented ant. It is concerned.

The composition for inhibiting fatty liver and renal hypertrophy due to diabetes according to claim 5, wherein the ginkgo biloba is a fermented ginkgo biloba extract obtained by fermenting an extract extracted from the ginkgo biloba. The present invention relates to a composition that suppresses fatty liver and renal hypertrophy.

The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 6, wherein the ginkgo biloba is a fermented ginkgo biloba extract obtained by fermenting an extract extracted from the ginkgo biloba. The present invention relates to a composition that suppresses fatty liver and renal hypertrophy.

The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 7, wherein the ginkgo biloba is a fermented ginkgo biloba extract obtained by fermenting an extract extracted from the ginkgo biloba. The present invention relates to a composition that suppresses fatty liver and renal hypertrophy.

The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 8, wherein the ginkgo biloba is a fermented ginkgo biloba extract obtained by fermenting an extract extracted from the ginkgo biloba. The present invention relates to a composition that suppresses fatty liver and renal hypertrophy.

Moreover, fermented earthworms are obtained by mixing earthworms in the fermentation broth obtained by inoculating yeast into the fruit and vegetable extract and fermenting the earthworms. According to a method for producing a composition for suppressing fatty liver and renal hypertrophy due to diabetes, characterized in that a composition that suppresses fatty liver and renal hypertrophy due to diabetes is obtained by mixing ants and ginkgo leaves in this fermentation mixture Is.

Since the present invention is configured as described above, the intake of the present invention can suppress the onset of fatty liver and renal hypertrophy that are highly likely to be caused by diabetes.

It is a graph which shows the measurement result of each organ weight of liver, a kidney, and the heart in Experiment 1 of a present Example, and the weight of the perirenal fat, and the epididymis fat. It is a graph which shows the liver weight per 100g of body weight in Test 1 of a present Example. It is an enlarged graph of the kidney weight in FIG. It is a graph which shows the ratio of the total lipid contained in the liver in Test 1 of a present Example. It is a graph which shows the weight of the total cholesterol contained in the liver in Test 1 of a present Example. It is a graph which shows the measurement result of urinary albumin in Test 1 of a present Example. It is a graph which shows the measurement result of the plasminogen activator inhibitor 1 (PAI-1) in Test 1 of a present Example. It is a graph which shows the measurement result of Euglobulin fraction dissolution time (ECLT) in Test 1 of a present Example. It is a graph which shows transition of the blood glucose level in Test 1 of a present Example. It is a graph which shows the measurement result of the glycohemoglobin (HbA1c) in Test 1 of a present Example. It is a graph which shows the measurement result of the insulin in Test 1 of a present Example. It is a graph which shows the measurement result of amylase in Test 1 of a present Example. It is a graph which shows the measurement result of uric acid in Test 1 of a present Example. It is a graph which shows the measurement result of glutamate oxaloacetyltransferase (GOT) in Test 1 of a present Example. It is a graph which shows the measurement result of alkaline phosphatase (ALP) in Test 1 of a present Example. It is a graph which shows the measurement result of lactate dehydrogenase (LD) in Test 1 of a present Example. It is a structure | tissue image which shows the result of having performed the systematic observation of the kidney section in Test 1 of a present Example. It is the graph which digitized the occupation rate of the mesangial matrix in a glomerulus from the structure | tissue image of FIG. It is a tissue image which shows the result of having conducted the systematic observation of the aortic arch in Test 1 of a present Example. FIG. 20 is a graph obtained by digitizing the blood vessel wall thickness of the aortic arch from the tissue image of FIG. 19. It is a graph which shows the weight change in Test 2 of a present Example. It is a graph which shows the measurement result of the glycohemoglobin (HbA1c) in Test 2 of a present Example. It is a graph which shows the measurement result of insulin in Test 2 of a present Example. It is a graph which shows the measurement result of adiponectin in Test 2 of a present Example. It is a graph which shows the measurement result of glutamate oxaloacetyltransferase (GOT) in Test 2 of a present Example. It is a graph which shows the measurement result of alkaline phosphatase (ALP) in Test 2 of a present Example. It is a graph which shows the measurement result of the leucine aminopeptidase (LAP) in Test 2 of a present Example. It is a graph which shows the measurement result of the blood total cholesterol in Test 2 of a present Example. It is a graph which shows the measurement result of blood urea nitrogen in Test 2 of a present Example. It is a graph which shows the measurement result of the creatinine clearance (Ccr) in Test 2 of a present Example. It is a graph which shows the measurement result of urinary albumin in Test 2 of a present Example. It is a graph which shows the measurement result of the liver weight in Test 2 of a present Example. It is a graph which shows the ratio of the total lipid contained in the liver in Test 2 of a present Example. It is a graph which shows the weight of the triglyceride contained in the liver in Test 2 of a present Example. It is a graph which shows the weight of the total cholesterol contained in the liver in Test 2 of a present Example. It is a graph which shows the measurement result of Euglobulin fraction dissolution time (ECLT) in Test 2 of a present Example. It is a graph which shows the measurement result of the plasminogen activator inhibitor 1 (PAI-1) in Test 2 of a present Example. It is a graph which shows the occupation ratio of the mesangial substrate in the glomerulus in Test 2 of a present Example.

Embodiments of the present invention that are considered to be suitable will be briefly described showing the operation of the present invention.

For example, by orally ingesting the composition for suppressing fatty liver and renal hypertrophy due to diabetes of the present invention, the lipid metabolic function decreased by diabetes is improved, and the decrease of lipid metabolic function by diabetes is suppressed.

Furthermore, microvascular disorders caused by diabetes are improved, and the onset of microvascular disorders caused by diabetes is suppressed (from the results of confirmation tests using ZDF rats (Zucker Diabetic Fatty Rat), which is a type II diabetes model rat). ).

This suppresses the onset or progression of fatty liver and renal hypertrophy due to diabetes.

Specific embodiments of the present invention will be described with reference to the drawings.

This example relates to a composition that uses earthworm as an active ingredient, and suppresses the onset of fatty liver and renal hypertrophy, which is likely to develop as a complication when developing type II diabetes, specifically, It consists of fermented liquor, rice field ginseng (also known as: 37 ginseng, scientific name: Panax motoginseng Berk), ants, and ginkgo leaves.

More specifically, the composition for suppressing fatty liver and renal hypertrophy due to diabetes (hereinafter referred to as “this composition”) in this example is mixed with earthworms in the fermentation broth obtained by inoculating the fruit and vegetable extract with yeast. Fermented earthworms are obtained by fermenting the earthworms. The fermented earthworms are mixed with rice ginseng and fermented and dried to obtain a fermented mixture. The fermented mixture is mixed with ants and ginkgo leaves.

Hereinafter, the composition will be described in detail.

The earthworm used in this example is the earthworm (scientific name: Eisenia fetida).

In addition, the fermented liquor is fermented by inoculating yeast extract (in this example, multiple types of yeasts, for example, opportunistic or Candida) into fruit and vegetable extracts extracted from fruits and vegetables such as vegetables and fruits, Specifically, sprouts 5 kg, cabbage 1.8 kg, Chinese cabbage 0.5 kg, spinach 0.5 kg, Komatsuna 0.5 kg, lotus root 0.6 kg, parsley 0.5 kg, potato 10 kg, pepper 2 kg, burdock 0.6 kg, papaya 45 kg, pineapple 15 kg, banana 2 kg, apple 5 kg, lemon 1 kg are cut into appropriate sizes, and 81 kg of anhydrous glucose, 9 kg of hydrous glucose and 0.2 l of yeast are added to the mixture and mixed with stirring. The fermented fermented product is squeezed with a press, and the squeezed fermented liquor is filtered (120 eyes).

In addition, the vegetables and fruits for obtaining the fruit and vegetable extract are not limited to the above, and other vegetables and fruits can be used.

In addition, the seven ginsengs are the seven ginsengs processed into powder.

Also, there are two types of ants, pseudo black multi-sword ants (scientific name: Polyrhachisviva Roger) and black ants (scientific name: Formica japonica). Specifically, these ants are fermented fermented ants.

More specifically, this fermented ant is papaya powder, powdered pseudo black multi-stab ant (hereinafter referred to as pseudo black multi-stab ant powder), powdered black ant (hereinafter referred to as black ant powder), Water is mixed, inoculated with yeast (raw yeast) and fermented, and the fermented product is dried and powdered.

More specifically, in a working room where the room temperature was set to 28 ° C., 38.2 kg of papaya powder, 1.82 kg of pseudo black multi-stab ant powder, 7.28 kg of black ant ant powder, and 44 l of water (40 ° C.) were mixed. Inoculated with 7.7 g of yeast (raw yeast), allowed to stand for 24 hours and fermented, dried at 25 ° C for 72 hours, and further dried at 21 ° C until the water content was 10% or less Then, this dried product with a water content of 10% or less is coarsely pulverized with a 2 mm mesh, and then finally pulverized with a 0.2 mm mesh to form a powder.

The papaya powder is prepared by slicing papaya by slicing or mincing, adding sugar to this to extract papaya extract, adding yeast to this papaya extract, and originally attaching to this yeast and this papaya. Fermented and proliferated with wild yeast, and lactic acid bacteria were added to this to separate the liquid from the yeast, wild yeast and lactic acid bacteria co-cultured, and yeast and lactic acid bacteria were further added to this liquid And fermented, matured and dried (see Kondo et al., Japanese Patent No. 3370302).

The ginkgo biloba is a ginkgo biloba extract extracted from ginkgo biloba, and specifically, a fermented ginkgo biloba extract obtained by fermenting this ginkgo biloba extract.

More specifically, the fermented ginkgo biloba extract is obtained by boiling the ginkgo biloba extract, extracting the extract, concentrating the extract by heating, mixing anhydrous glucose and fermented calcium into the concentrated extract, and then adding the yeast. Inoculated and fermented, the fermented product is dried and powdered.

More specifically, 50 kg of ginkgo leaves and 500 liters of water are put into a kneader, heated and boiled for 1 hour to extract the extract, and the extracted extract is filtered through # 350 and # 500 nets. The extracted extract was heated, concentrated to 60 l, mixed with 17.5 kg of anhydrous glucose while the liquid temperature of this concentrated extract was high, and further mixed with 5 kg of fermented calcium at a liquid temperature of 30 ° C. And fermented aerobically for 24 hours in a working room set at a room temperature of 28 ° C., and after fermentation, kept at a room temperature of 23 to 24 ° C. and dried. During drying, 5 kg of brown rice and starch ( In this example, powdered starch is used) 22.5 kg is mixed in half amounts in two days, the room temperature is lowered to 20 ° C. from the next day after the mixing operation is completed, and the moisture content is reduced to 5% or less, This dried too After coarsely pulverized by 2mm mesh is obtained by the powder to the ground in a 0.2mm mesh.

The fermented calcium is a fermented liquid having a fermentation period of 2 weeks in the above-mentioned fermented liquid, and calcium powder (70 wt% of Hokuriku shell fossil, shelled calcium with respect to 1 liter of the fermented liquid). 28 wt% and 2 wt% fish calcium) and stirred for about 2 weeks, and this is mixed with kumbu extract at a rate of 5.5 ml per 1 l of fermentation broth, and at a rate of 0.2 l per 1 l of fermentation broth. (In this example, a mixture of kombu extract and water is added to the fermentation broth.) The day after adding the kombu extract and water, the room temperature is raised to 25 ° C., and the room temperature is set again the next day. The temperature is lowered to 21 ° C. and dried until the water content becomes 8% or less. The dried product is coarsely pulverized with a 2 mm mesh, and then main pulverized with a 0.2 mm mesh to obtain a powder.

Next, the method for producing the composition will be specifically described. In addition, the following description is a case where 1 kg of earthworm (100 g after drying, blending ratio 15 wt%) is used.

First, the earthworm is mud, washed, and then pulverized to a particle size of 2 mm or less.

Specifically, mud is taken out into the mixer, and the washed earthworm and water (adding 3.5 liters of water to 1 kg of the earthworm weight) are added and pulverized with a mixer for 40 to 80 minutes, so-called mud-like earthworm Get. During the pulverization process, the liquid temperature rises, and if the increased liquid temperature exceeds 30 ° C., the active component of the earthworm may be altered or destroyed. The temperature of the added water is preferably 15 ° C. or less so as not to exceed ℃.

Next, 215 ml of fermented liquor (mixing ratio 20 wt%) and 125 ml of lactic acid bacteria are mixed with this ground and mud-shaped striped earthworm, left at 25 ° C. for 17 to 21 hours, and fermented to obtain fermented earthworm. In this example, K-1 bacterium or Leuconostoc mesenteroides having a good antibacterial effect is used as the lactic acid bacterium, but the type of lactic acid bacterium used is to suppress the growth of Escherichia coli and coliforms. There is no particular limitation as long as these can be killed in the drying process.

Next, 180 g of ginseng powder (mixing ratio 27 wt%) is mixed with this fermented striped earthworm, and this mixed first mixture is dried until it is free from moisture while being fermented.

Specifically, it is fermented and dried for 48 to 72 hours while keeping the room temperature at 23 ° C. and blowing to the first mixture (by the action of the lactic acid bacteria mixed when creating the fermented earthworm at this stage of fermentation drying, Escherichia coli and coliforms are sterilized.) After the fermentation and drying, the water content of the first mixture is air-dried for about 2 weeks while keeping the room temperature at 20 to 28 ° C. and the humidity at 18% or less. Dry until 5% or less.

Next, the dried first mixture is mixed with 20 g of powdered fermented ants (blending ratio 3 wt%) and 233 g of fermented ginkgo biloba extract (blending ratio 35 wt%) to obtain a second mixture.

Finally, this second mixture is coarsely pulverized with a 2 mm mesh, and finally pulverized with a 0.2 mm mesh to form a powder, and this powder is accommodated in a capsule to be completed. The final form is not limited to the capsule form, and may be a powder or a tablet.

In this example, each component (material) is blended in the above-mentioned blending ratio, but fermented striped earthworm 12-18 wt%, rice ginseng powder 22-32 wt%, fermented ant 2-4 wt%, fermented ginkgo biloba The extract can be appropriately changed within the range of 28 to 42 wt% of the extract and 16 to 24 wt% of the fermentation broth.

Next, the effect of this composition will be described.

In this example, two effect confirmation tests, Test 1 and Test 2, were performed. In Test 1, the effect of this composition is simply confirmed, and in Test 2, the effects of the earthworm (shimworm) component and other components that could not be confirmed in Test 1 and the effect of early symptoms are confirmed. It was. First, Test 1 will be described in detail.

≪Test 1≫
In this test, a ZDF rat (Zucker Diabetic Fatty Rat), which is a type II diabetes model rat, was used to give a ZDF rat fed with a normal feed not containing the above composition, and a feed containing this composition. The effect of this composition was confirmed by comparing the difference in state with ZDF rats.

Specifically, ZDF rats were prepared as 20 male 7-week-old males, and these were divided into two groups of 10 animals so that the average body weight and blood glucose level were almost equal. A control group (hereinafter referred to as C group) that gives a normal feed (control feed) that does not contain the composition, and the other group is an Eisenia fetida group (hereinafter referred to as an EF group) that receives feed containing the composition. It was called.)

The normal feed given to Group C is a feed prepared by using casein as a protein source in accordance with AIN-93G. The feed given to Group EF is 5% of corn starch contained in the normal feed given to Group C. % (Weight) is a feed in which the composition is replaced.

Also, as a feeding method, each group was fed with each feed for 12 weeks (7 to 19 weeks old) by pair feeding. In addition, in order to measure the fasting blood glucose level once a week for free intake of water, fasting was performed for 18 hours before the measurement.

GDF, glycohemoglobin (hereinafter referred to as HbA1c), insulin, organ weight (kidney, liver, heart, perirenal fat, accessory testicular circumference) Fat), euglobulin fraction dissolution time (hereinafter referred to as ECLT), blood components, and histological observation of kidney sections and aortic arch, and comparison between group C and EF group, The effect was confirmed.

FIGS. 1 to 3 are graphs showing the measurement results of the weights of the organs of the kidney, liver, and heart, and the weights of perirenal fat and epididymal fat.

In the measurement of the weight of the organ or the like, as shown in FIG. 1, there was a significant difference (t test, p <0.01) between the kidney and the liver (for the heart, perirenal fat and accessory testicular fat, No significant difference between group C and EF).

Specifically, as is clear from the measurement results of the liver weight shown in FIG. 2 and the measurement results of the kidney weight shown in FIG. 3, a significant difference (t test, p <0. 01), and the EF group showed lower values for both the liver weight and the kidney weight than the C group.

FIG. 4 is a graph showing the weight of total lipid contained in the liver, and FIG. 5 is a graph showing the weight of total cholesterol (T-cho) contained in the liver.

In the measurement of the weight of total lipid and total cholesterol contained in the liver, there is a significant difference between the C group and the EF group (t test, p <0.01) for both the total lipid and total cholesterol. The EF group showed lower values for both total lipid and total cholesterol. For reference, normal rats (healthy rats) have about 4% total liver lipids and about 0.4% total cholesterol based on the total weight of the liver.

From the measurement result of the liver weight shown in FIG. 2, the measurement result of the total lipid weight of the liver shown in FIG. 4, and the measurement result of the total cholesterol weight of the liver shown in FIG. When the ratios of total lipid and total cholesterol were calculated, the ratio of total lipid and total cholesterol to liver weight in group C was higher than that of normal rats. And the ratio of the total cholesterol was a value equivalent to a normal rat.

From this result, it is considered that the reason why the liver weight of the ZDF rats in the EF group was significantly lower than the liver weight of the ZDF rats in the C group was due to the difference in the total lipids and total cholesterol in the livers.

That is, the ZDF rats in the EF group were ingested this composition because the lipid metabolism function that was reduced by diabetes was improved by the intake of this composition, and lipid metabolism in a state close to normal was performed. As a result, the lipid metabolism function due to diabetes was suppressed and normal lipid metabolism was performed, so that the accumulation of fat in the liver was suppressed, the total lipid and cholesterol in the liver did not increase, and the liver weight It is considered that the results showed almost the same value as that of normal rats.

FIG. 6 is a graph showing the measurement results of urinary albumin.

In the measurement of urinary albumin, there was no significant difference between the C group and the EF group from the start of the test (7 weeks of age) to the 6th week (13 weeks of age), but 8 weeks after the start of the test. There is a significant difference (t test, p <0.05) between the C group and the EF group in the eyes (15 weeks of age), and the EF group shows a lower value of urinary albumin than the C group In addition, after 10 weeks (17 weeks of age) after the start of the test, there was no significant difference again. However, from around the 4th week of the test to the end of the test, the EF group had a lower urinary albumin value than the C group, and a tendency to suppress the excretion of albumin was observed.

In general, as diabetes progresses, diabetic nephropathy often develops as a complication, and when diabetic nephropathy develops, it is known that albumin that is hardly released in the urine is leaked. It is considered effective for the determination of early diabetic nephropathy, and this urinary leakage of albumin is considered to be caused by microangiopathy caused by diabetes.

That is, it is considered that the ZDF rats in the EF group have increased fibrinolytic ability by ingesting this composition, and the amount of urinary albumin is lower than that in the C group due to the effect of improving microangiopathy.

In addition, the reason why the kidney weight of the ZDF rats in the EF group that took this composition was significantly lower than the kidney weight of the ZDF rats in the C group that did not take this composition was the increased fibrinolytic ability. This is considered to be because the onset of microangiopathy due to diabetes was suppressed and the renal function did not decrease, and the symptoms of renal hypertrophy were improved or suppressed.

FIG. 7 is a graph showing the measurement results of plasminogen activator inhibitor 1 (hereinafter referred to as PAI-1) in blood.

In the measurement of PAI-1, there is a significant difference (t test, p <0.05) between the C group and the EF group, and the PAI-1 value is lower in the EF group than in the C group. The result was shown.

In this PAI-1, lipid metabolism decreases due to diabetes, and fat cells are enlarged due to visceral fat accumulation due to the decrease in lipid metabolism, resulting in an increase in the amount of release. When the amount of PAI-1 released increases It is known that the fibrinolytic ability is lowered and thrombi are easily formed.

That is, the measurement result of PAI-1 also confirms that the present composition has an effect of improving lipid metabolism reduced by diabetes and suppressing a decrease in fibrinolysis caused by diabetes.

FIG. 8 is a graph showing the measurement results of ECLT. In this ECLT measurement, healthy rats that did not develop diabetes other than the ZDF rats of the C group and the EF group, specifically, SD rats were used, and the ECLT value of the SD rats was used as a benchmark. The ECLT values of rats were compared with the ECLT values of the C group and the EF group.

This ECLT evaluates the fibrinolytic ability by adding thrombin, a blood coagulation factor, to the euglobulin fraction, artificially creating a thrombus, and measuring the time until this coagulation dissolves. This indicates that the longer the is, the lower the fibrinolytic ability.

In this test, as shown in FIG. 8, there is a significant difference between the C group and the EF group (t test, p <0.01), and the EF group to which the present composition was given was more ECLT than the C group. It was also confirmed that the ECLT value of the ZDF rats in the EF group given this composition showed the same value as the ECLT value of healthy SD rats.

From the ECLT measurement results, it was also confirmed that the present composition may have an effect of improving the fibrinolytic ability decreased by diabetes or an effect of suppressing the decrease of fibrinolytic ability by diabetes.

That is, generally, when diabetes develops, it becomes a problem that thrombosis develops as a complication, but this composition may also exert an effect of suppressing the development of thrombosis due to diabetes. Was confirmed.

FIG. 9 is a graph showing the transition of fasting blood glucose level, and FIG. 10 is a graph showing the result of measuring HbA1c.

Since HbA1c is generally more likely to be formed as the blood glucose level is higher, when it develops diabetes, it significantly increases as the blood glucose level increases.

In this test, both the blood glucose level and HbA1c were not significantly different between the C group and the EF group, and both groups showed high values in both the blood glucose level and HbA1c. In addition, the value of HbA1c in normal ZDF rats is about 9.4% at 18 weeks of age (refer to the data of Charles River Japan). However, it was determined that there was no problem with the HbA1c value because it was confirmed that the hyperglycemic state was maintained from the measurement result of the blood glucose level.

FIG. 11 is a graph showing the results of measuring insulin.

In the ZDF rat, excessive secretion of insulin occurs in the early stage of diabetes, but it is known that the secretory ability is lost around 18 weeks of age and the insulin concentration is lowered.

In this test, as shown in FIG. 11, the EF group ingesting the composition showed a slightly higher insulin secretion ability, but there was no significant difference between the C group and the EF group. there were.

From the measurement results of blood glucose level, HbA1c, and insulin, it can be seen that the present composition does not directly act on the improvement mechanism of blood glucose level.

That is, this composition does not suppress the development of fatty liver and renal hypertrophy caused by diabetes by improving the symptoms of hyperglycemia, but directly acts on the function of the liver and kidneys and is reduced by diabetes. It is considered to have an effect of improving lipid metabolism function and kidney function, or an effect of suppressing a decrease in liver lipid metabolism function and kidney function due to diabetes.

In this test, total protein (TP), albumin (Alb), zinc sulfate turbidity test (ZTT), thymol turbidity test (TTT), total bilirubin (T-BIL), glutamate oxaloacetate transferase (GOT), glutamate Pyruvate transferase (GPT), alkaline phosphatase (ALP), lactate dehydrogenase (LD), gamma-glutamic acid (γ-GT), leucine aminopeptidase (LAP), cholinesterase (CHE), creatine kinase (CK), Acid phosphatase (ACP), amylase (AMY), uric acid (UA), urea nitrogen (BUN), creatinine (Cre), serum iron (Fe), total cholesterol (T-cho), neutral fat (TG), HDL cholesterol For 24 items (HDL), arteriosclerosis index (AI), and LDL cholesterol (LDL), measurement and analysis were performed by blood test.

In these 24 items, there was a significant difference (t test, p <0.01) between the C group and the EF group in two items of amylase and uric acid.

Amylase is an item that tends to be high during diabetes or renal failure, but in this study, as shown in FIG. 12, the EF group showed a significantly lower value. It can be presumed that the present composition has an effect of suppressing or delaying the onset of diabetic nephropathy or an effect of improving the symptoms of diabetic nephropathy.

In addition, the uric acid level is an item that becomes high due to metabolic syndrome or the like, but in this test, as shown in FIG. 13, the EF group showed a significantly lower value. It is considered that the results may have some influence on the metabolic system of uric acid.

Although there is no significant difference, as shown in FIGS. 14 to 16, the EF group has better values in three items of glutamate oxaloacetyltransferase (GOT), alkaline phosphatase (ALP), and lactate dehydrogenase (LD). It was the result which showed. This is considered to be a result suggesting that the present composition may have suppressed the decrease in liver function or may have improved the decreased liver function.

FIG. 17 is a tissue image showing the result of the tissue observation of the kidney section, and FIG. 18 is a graph obtained by quantifying the tissue image.

In the histological observation of this kidney section, as shown in FIG. 17, suppression of an increase in mesangial matrix was observed in the EF group ingesting the present composition.

In addition, as a result of comparing the observed tissue images with numerical values, there is a significant difference (t test, p <0.05) between the C group and the EF group, and the EF group is more stringent than the C group. The results show that the proportion of the mesangial substrate in the sphere area is small, that is, the increase in the mesangial substrate is suppressed.

This mesangial matrix normally plays a role in supporting the glomeruli in the kidney, but it is known that the mesangial matrix is enlarged due to hyperglycemia in diabetes and presses the surrounding glomerular capillaries. However, in Group C that did not take this composition, the same tendency was observed, but in the EF group that took this composition, this increase in mesangial matrix was suppressed, and glomerular capillaries were observed. No pressure symptoms were seen.

Capillary blood vessels compressed by the mesangial matrix have a narrow lumen (blood passage) and worse blood flow, but the glomerulus filters the blood that flows in, so the blood flow deteriorates and the filtration function is reduced. Furthermore, the walls of the capillaries have pores that filter blood, which serves as a filter, but the walls become thicker and coarser, resulting in large amounts of protein leaking, resulting in proteinuria. Come out.

In this test, albuminuria in the EF group was suppressed because the enlargement of the mesangial substrate was suppressed.

FIG. 19 is a tissue image showing the result of systematic observation of the aortic arch, and FIG. 20 is a graph in which the arterial arch wall thickness is digitized from the tissue image.

In the systematic observation of the aortic arch, as shown in FIG. 19, it was observed that suppression of hypertrophy of the vascular wall of the aortic arch tends to be significant in the EF group ingested with the present composition.

In addition, as a result of comparing the observed tissue images with numerical values, the EF wall thickness is thinner than the C group and there is no significant difference, but hypertrophy is suppressed with a numerically significant tendency. I was able to confirm.

Next, Test 2 will be described in detail.

≪Test 2≫
This test will clarify the effects of the earthworm (spotted earthworm) component in this composition and the effects of ingredients other than the earthworm (spotted earthworm), and confirm the effect on early symptoms by setting the test period to a short period. The purpose is to do.

Specifically, as in Test 1, ZDF rats were used, ZDF rats fed with a normal feed not containing this composition, ZDF rats fed with a feed containing this composition, and earthworms (Shimwort) in this composition. ) The difference in the state of ZDF rats fed with a feed containing a composition containing no earthworm containing no ingredients was compared, and the effects of the ingredients other than the earthworm component and the earthworm component in this composition were clarified. In addition, the said earthworm-free composition is a composition obtained by simply removing the earthworm component in the present composition, and the blending ratio of the other components is the same as that of the present composition.

Specifically, ZDF rats are prepared as 7-week-old males as in Test 1, and contain the same composition as in Test 1 so that the average body weight and blood glucose level are almost equal. Group C that gives normal feed (control feed) that does not, EF group that gives feed containing this composition, and Non-Eisenia fetida group (hereinafter referred to as NE group) that gives feed containing a composition containing no earthworms. ).

The feed given to the C group and the EF group is the same as in the test 1, and the feed given to the NE group contains 4.25% (weight) of corn starch contained in the normal feed given to the C group without earthworms. It is the feed replaced with the composition.

In addition, all feeding methods were performed under the same conditions as in Test 1 except that the test period was 10 weeks (7 to 17 weeks old).

With respect to each of the ZDF rats of group C, EF group and NE group bred under the above conditions, body weight change, HbA1c, insulin, adiponectin, liver function marker (blood), blood total cholesterol, liver lipid, ECLT, PAI- 1. Measure mesangial substrate ratio and compare between C group, EF group and NE group to clarify the effects of earthworm (shimworm) component and other ingredients in this composition. The effect on the symptom was confirmed.

FIG. 21 is a graph showing changes in body weight. As shown in FIG. 21, the C group showed almost no increase in body weight from around the 5th week (12 weeks of age), and after the 6th week (13 weeks of age), there was a significant difference between the EF group and the NE group (LSD). There was a test, p <0.01), which resulted in a significant difference in growth reduction (no significant difference between EF and NE groups).

FIG. 22 is a graph showing the results of measuring HbA1c. In Study 1, there was no significant difference between the C group and the EF group, but in this study, there was a significant difference (LSD test, p <0.05) between the C group and the EF group, and between the C group and the NE group. ), And the HbA1c value was significantly suppressed between the EF group and the NE group (there was no significant difference between the EF group and the NE group). This is thought to be due to the fact that this study looks at the HbA1c value at an early stage of diabetes.

Moreover, since the HbA1c value was suppressed even in the NE group that did not contain the earthworm component, it was confirmed that components other than the earthworm component had the effect of suppressing the HbA1c value.

FIG. 23 is a graph showing the results of measuring insulin. As in Test 1, there was no significant difference between the C group and the EF group, and there was no significant difference between the C group and the NE group and between the EF group and the NE group.

FIG. 24 is a graph showing the results of measuring adiponectin (a new item not measured in Test 1). As shown in FIG. 24, there is a significant difference (LSD test, p <0.05) between the C group, the EF group, and the NE group, and the result that the adiponectin value is significantly higher between the EF group and the NE group. (There was no significant difference between the EF group and the NE group).

This adiponectin is a good adipokine that is known to decrease during diabetes, and is associated with insulin resistance and the like, and has a blood glucose lowering effect. It is also said that adiponectin decrease causes arteriosclerosis.

In addition, since the value of adiponectin is high even in the NE group that does not contain the earthworm (shimus earthworm) component, it was confirmed that the components other than the earthworm (shimworm) component have an effect of suppressing the reduction of adiponectin. In addition, it is thought that the effect which suppresses the HbA1c value mentioned above is the result which arose by improving insulin resistance by suppressing this reduction | decrease of adiponectin.

25 to 27 are graphs showing the measurement results of liver function markers (in blood). Specifically, FIG. 25 shows glutamate oxaloacetate transferase (GOT), and FIG. 26 shows alkaline phosphatase (ALP). FIG. 27 is a graph showing the measurement results of leucine aminopeptidase (LAP). FIG. 28 is a graph showing the measurement results of blood total cholesterol.

Leucine aminopeptidase, one of the liver function markers, is known to increase in liver disease, and is also known to increase in fatty liver. In addition, blood total cholesterol is an item that is known to increase as diabetes progresses.

In Test 1, there was no significant difference between each item (glutamate oxaloacetyltransferase and alkaline phosphatase showed a significant tendency). However, in this test, as shown in FIGS. In both cases, there was a significant difference (LSD test, p <0.05) between the C group, the EF group, and the NE group.

That is, in this study, the increase in liver function markers glutamate oxaloacetyltransferase, alkaline phosphatase, and leucine aminopeptidase was significantly suppressed and the increase in blood total cholesterol was significantly increased in the EF group and the NE group. It was suppressed, and the results showed that liver function decrease was significantly suppressed and lipid metabolism was improved between EF group and NE group (no significant difference between EF group and NE group).

In addition, since the NE group that does not contain the earthworm component was significantly different from the group C in each item, the components other than the earthworm component were suppressed in reducing liver function and improved lipid metabolism. It was confirmed that there was an effect.

29 and 30 are graphs showing the measurement results of renal function markers. Specifically, FIG. 29 shows blood urea nitrogen (BUN), and FIG. 30 shows the measurement results of creatinine clearance (Ccr). It is a graph to show.

These renal function markers, blood urea nitrogen and creatinine clearance, are both items used as indicators of renal function during diabetes, and blood urea nitrogen increases when the renal filtration function decreases. In addition, creatinine clearance represents the filtration capacity of the kidney, and is an item that is known to decrease with the progression of diabetic nephropathy.

In test 1, there was no significant difference in the measurement results of blood urea nitrogen, but in this test, there was a significant difference (LSD test, p <0.05) between group C, EF group, and NE group. . Further, regarding creatinine clearance, although there was no significant difference, there was a significant tendency between the C group, the EF group, and the NE group.

That is, in this test, in the EF group and the NE group, the increase in blood urea nitrogen as a renal function marker tends to be significantly suppressed, and the decrease in creatinine clearance tends to be suppressed. Thus, the results suggested the effect of suppressing the decrease in renal function (no significant difference between the EF group and the NE group).

FIG. 31 is a graph showing the results of measuring urinary albumin.

In Study 1, a significant difference was observed 8 weeks after the start of the study. In this study, a significant difference (LSD) was observed between the C group, the EF group, and the NE group from the 6th week (13 weeks of age) after the start of the study. Test, p <0.05), and finally (10 weeks after the start of the test), each group had a significant difference (LSD test, p <0.05).

Specifically, the leakage amount of urinary albumin was significantly suppressed in the EF group than that of the C group, and the leakage amount of urinary albumin was significantly suppressed in the NE group than in the EF group. . From this, it was confirmed that the components other than the earthworm (spotted earthworm) component have an effect of suppressing leakage of urinary albumin.

FIGS. 32 to 35 are graphs showing measurement results regarding liver lipids, FIG. 32 shows measurement results of liver weight, FIG. 33 shows measurement results of total liver lipids, and FIG. The measurement result of the weight of triglyceride in the liver is shown, and FIG. 35 is a graph showing the measurement result of the weight of total cholesterol in the liver.

In the measurement of liver weight, there is a significant difference (LSD test, p <0.05) between group C, EF group and NE group (no significant difference between EF group and NE group), and measurement of total liver lipids Then, there was a significant difference (LSD test, p <0.05) between the C group, the NE group, and the EF group (the C group and the NE group had no significant difference).

Moreover, in the measurement of the triglyceride weight in the liver, there is a significant difference (LSD test, p <0.05) between the C group, the NE group and the EF group (the C group and the NE group have no significant difference), In the measurement of total cholesterol weight, there was a significant difference (LSD test, p <0.05) between each group.

Specifically, the NE group showed a significantly lower total cholesterol value than the C group, and the EF group showed a significantly lower total cholesterol value than the NE group.

From this, it was confirmed that the earthworm component has the effect of suppressing lipid accumulation in the liver.

FIG. 36 is a graph showing the measurement result of ECLT, and FIG. 37 is a graph showing the measurement result of PAI-1.

Similar to Test 1, in this test, the measurement result of ECLT has a significant difference (LSD test, p <0.05) between the C group and the EF group, and the ECLT is lower in the EF group than in the C group. The result showed a value. The NE group had no significant difference with respect to both the C group and the EF group.

As for PAI-1, as in Test 1, there is a significant difference between the C group and the EF group (LSD test, p <0.01), and the PAI-1 is lower in the EF group than in the C group. In addition, in the NE group, as in the EF group, there is a significant difference (LSD test, p <0.01) from the C group, and the PAI-1 value is lower than that in the C group. (There was no significant difference between the EF group and the NE group).

From the ECLT and PAI-1 measurement results, it can be confirmed that the earthworm (Shimizumi) component has an effect of significantly suppressing the decrease in the fibrinolytic function during diabetes, and the components other than the earthworm (Shimizumi) component are fibrinolytic. It was confirmed that the inhibitory factor (PAI-1) was effective.

FIG. 38 is a graph showing the occupation ratio of the mesangial substrate in the glomerulus.

As in Test 1, there is a significant difference between the C group and the EF group (LSD test, p <0.05), and the EF group has a smaller proportion of the glomerular area than the C group, ie, The result showed that the increase in mesangial substrate was suppressed.

In this test, there is a significant difference (LSD test, p <0.05) between the C group and the NE group, and further, a significant difference (LSD test, p <0.05) between the NE group and the EF group. 0.05). That is, the increase in mesangial substrate was most suppressed in the EF group, and then the increase in mesangial substrate was suppressed in the NE group. From this, it was confirmed that the earthworm component contributes greatly in suppressing the change in the tissue structure of the kidney.

As described above, from the results of Test 1 and Test 2 described above, it was confirmed that this composition has an action of suppressing diabetic complications (improvement of lipid metabolism, suppression of progression of diabetic nephropathy).

In addition, the effect of improving the liver lipid metabolism, the enhancement of fibrinolytic function, and the suppression of changes in the renal tissue structure can be confirmed by the action of earthworms in this composition. In addition, it was confirmed that the action by components other than the earthworm (Shima earthworm) components (Tanachi ginseng, fermented ants, fermented ginkgo biloba extract, fermentation broth) was great.

Thus, this composition can suppress fatty liver and renal hypertrophy due to type II diabetes by the action of each component of earthworms (spotted earthworm), ginseng, fermented ants, fermented ginkgo biloba extract, and fermentation broth. It will be a breakthrough that has never existed before.

Moreover, in addition to the effects described above, the present composition exhibits anti-inflammatory effects and analgesic effects by the action of fermenting ants, and can also be expected to have an effect of alleviating various diseases caused by diabetes.

Note that the present invention is not limited to this embodiment, and the specific configuration of each component can be designed as appropriate.

Claims

A composition for suppressing fatty liver and renal hypertrophy due to diabetes, comprising earthworm as an active ingredient.
The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 1, wherein the earthworm is a fermented earthworm fermented with a fermentation broth obtained by inoculating a fruit extract with yeast. A composition that suppresses fatty liver and renal hypertrophy.
2. The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 1, wherein the earthworm is an earthworm.
3. The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 2, wherein the earthworm is a worm earthworm.
The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to any one of claims 1 to 4, comprising at least one kind of ginseng, ants, and ginkgo leaves. A composition that suppresses renal hypertrophy.
The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to any one of claims 1 to 4, comprising a ginseng, ants and ginkgo leaves, wherein Inhibiting composition.
6. The composition for suppressing fatty liver and kidney enlargement due to diabetes according to claim 5, wherein the ant is a fermented fermented ant.
7. The composition for suppressing fatty liver and kidney enlargement due to diabetes according to claim 6, wherein the ant is a fermented fermented ant.
The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 5, wherein the ginkgo biloba is a fermented ginkgo biloba extract obtained by fermenting an extract extracted from this ginkgo biloba. And a composition that suppresses renal hypertrophy.
The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 6, wherein the ginkgo biloba is a fermented ginkgo biloba extract obtained by fermenting an extract extracted from this ginkgo biloba leaf. And a composition that suppresses renal hypertrophy.
The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 7, wherein the ginkgo biloba is a fermented ginkgo biloba extract obtained by fermenting an extract extracted from this ginkgo biloba. And a composition that suppresses renal hypertrophy.
The composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 8, wherein the ginkgo biloba is a fermented ginkgo biloba extract obtained by fermenting an extract extracted from the ginkgo biloba. And a composition that suppresses renal hypertrophy.
Fermented earth obtained by inoculating yeast into the fruit and vegetable extract, fermented by mixing earthworms and fermenting the earthworms, mixed with fermented ginseng and fermented and dried to obtain a fermentation mixture, A method for producing a composition for inhibiting fatty liver and renal hypertrophy due to diabetes, comprising mixing this ant and ginkgo biloba with the fermentation mixture to obtain a composition for inhibiting fatty liver and renal hypertrophy due to diabetes.