WO2015152045A1 - Composition inhibant la stéatose hépatique et la néphromégalie provoquées par le diabète et procédé de production de celle-ci - Google Patents

Composition inhibant la stéatose hépatique et la néphromégalie provoquées par le diabète et procédé de production de celle-ci Download PDF

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WO2015152045A1
WO2015152045A1 PCT/JP2015/059604 JP2015059604W WO2015152045A1 WO 2015152045 A1 WO2015152045 A1 WO 2015152045A1 JP 2015059604 W JP2015059604 W JP 2015059604W WO 2015152045 A1 WO2015152045 A1 WO 2015152045A1
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composition
group
fermented
fatty liver
diabetes
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PCT/JP2015/059604
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English (en)
Japanese (ja)
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基二 門脇
真敏 久保田
近藤　堯
智子 川上
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国立大学法人新潟大学
株式会社ミヤトウ野草研究所
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Priority to KR1020167030383A priority Critical patent/KR101873141B1/ko
Priority to CN201580017620.9A priority patent/CN106470692B/zh
Priority to SG11201606837XA priority patent/SG11201606837XA/en
Publication of WO2015152045A1 publication Critical patent/WO2015152045A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • 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.
  • 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 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.
  • composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 1, wherein the earthworm is a worm earthworm.
  • composition for suppressing fatty liver and renal hypertrophy due to diabetes according to claim 2, wherein the earthworm is a worm earthworm.
  • 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.
  • present invention relates to a composition that suppresses liver and kidney hypertrophy.
  • composition for suppressing fatty liver and kidney enlargement due to diabetes comprising a ginseng, an ant and a ginkgo leaf.
  • the present invention relates to a composition that suppresses hypertrophy.
  • 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.
  • 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.
  • composition for suppressing fatty liver and renal hypertrophy due to diabetes 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 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.
  • 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.
  • 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.
  • 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.
  • PAI-1 plasminogen activator inhibitor 1
  • ECLT Euglobulin fraction dissolution time
  • 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.
  • HbA1c glycohemoglobin
  • GTT glutamate oxaloacetyltransferase
  • ALP alkaline phosphatase
  • LAP leucine aminopeptidase
  • Ccr creatinine clearance
  • ECLT Euglobulin fraction dissolution time
  • the composition for suppressing fatty liver and renal hypertrophy due to diabetes of the present invention 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.
  • 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 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.
  • rice field ginseng also known as: 37 ginseng, scientific name: Panax motoginseng Berk
  • ants and ginkgo leaves.
  • this composition 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.
  • the earthworm used in this example is the earthworm (scientific name: Eisenia fetida).
  • 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.
  • yeast extract in this example, multiple types of yeasts, for example, opportunistic or Candida
  • 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.
  • the seven ginsengs are the seven ginsengs processed into powder.
  • pseudo black multi-sword ants (scientific name: Polyrhachisviva Roger) and black ants (scientific name: Formica japonica). Specifically, these ants are fermented fermented ants.
  • 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.
  • pseudo black multi-stab ant powder powdered pseudo black multi-stab ant
  • black ant powder powdered black ant
  • Water is mixed, inoculated with yeast (raw yeast) and fermented, and the fermented product is dried and powdered.
  • 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.
  • 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.
  • 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.
  • the earthworm is mud, washed, and then pulverized to a particle size of 2 mm or less.
  • 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.
  • 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 °C.
  • 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.
  • the first mixture 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.)
  • 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.
  • 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.
  • 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.
  • 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.
  • Test 1 two effect confirmation tests, Test 1 and Test 2, were performed.
  • 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.
  • 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.
  • 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
  • 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.
  • each group was fed with each feed for 12 weeks (7 to 19 weeks old) by pair feeding.
  • fasting was performed for 18 hours before the measurement.
  • GDF glycohemoglobin
  • HbA1c glycohemoglobin
  • insulin an enzyme that stimulates the production of glucose
  • organ weight kidney, liver, heart, perirenal fat, accessory testicular circumference
  • Fat euglobulin fraction dissolution time
  • ECLT euglobulin fraction dissolution time
  • 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.
  • FIG. 4 is a graph showing the weight of total lipid contained in the liver
  • FIG. 5 is a graph showing the weight of total cholesterol (T-cho) contained in the liver.
  • 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.
  • 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.
  • 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.
  • diabetic nephropathy 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.
  • 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.
  • FIG. 7 is a graph showing the measurement results of plasminogen activator inhibitor 1 (hereinafter referred to as PAI-1) in blood.
  • 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.
  • 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.
  • 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.
  • FIG. 9 is a graph showing the transition of fasting blood glucose level
  • FIG. 10 is a graph showing the result of measuring HbA1c.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • GAT glutamate oxaloacetyltransferase
  • ALP alkaline phosphatase
  • LD lactate dehydrogenase
  • FIG. 17 is a tissue image showing the result of the tissue observation of the kidney section
  • FIG. 18 is a graph obtained by quantifying the tissue image.
  • 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.
  • 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.
  • 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
  • FIG. 20 is a graph in which the arterial arch wall thickness is digitized from the tissue image.
  • 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.
  • 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.
  • 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
  • NE group Non-Eisenia fetida group
  • 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.
  • 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.
  • 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.
  • 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.
  • adiponectin 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
  • FIG. 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.
  • GAT glutamate oxaloacetate transferase
  • ALP alkaline phosphatase
  • 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.
  • blood total cholesterol is an item that is known to increase as diabetes progresses.
  • 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).
  • 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.
  • FIG. 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.
  • BUN blood urea nitrogen
  • Ccr creatinine clearance
  • renal function markers blood urea nitrogen and creatinine clearance
  • blood urea nitrogen increases when the renal filtration function decreases.
  • creatinine clearance represents the filtration capacity of the kidney, and is an item that is known to decrease with the progression of diabetic nephropathy.
  • 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.
  • FIG. 31 is a graph showing the results of measuring urinary albumin.
  • 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
  • FIG. The measurement result of the weight of triglyceride in the liver is shown
  • FIG. 35 is a graph showing the measurement result of the weight of total cholesterol in the liver.
  • the NE group showed a significantly lower total cholesterol value than the C group
  • the EF group showed a significantly lower total cholesterol value than the NE group.
  • the earthworm component has the effect of suppressing lipid accumulation in the liver.
  • FIG. 36 is a graph showing the measurement result of ECLT
  • FIG. 37 is a graph showing the measurement result of PAI-1.
  • 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.
  • 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).
  • 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.
  • this composition has an action of suppressing diabetic complications (improvement of lipid metabolism, suppression of progression of diabetic nephropathy).
  • 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.
  • the action by components other than the earthworm (Shima earthworm) components was great.
  • 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.
  • 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.

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Abstract

La présente invention a pour objet une composition qui comprend le ver de terre en tant que principe actif et peut inhiber la stéatose hépatique et la néphromégalie qui sont susceptibles d'être induites par le diabète. La composition, qui inhibe la stéatose hépatique et la néphromégalie provoquées par le diabète, est préparée par : l'inoculation d'un extrait de fruits et de légumes par des levures pour obtenir une liqueur fermentée ; l'ajout de vers de terre à la liqueur fermentée et la fermentation des vers de terre pour obtenir des vers de terre fermentés ; l'ajout aux vers de terre fermentés de Panax notoginseng suivi de la fermentation et du séchage pour obtenir un mélange fermenté ; et le mélangeage du mélange fermenté avec des fourmis et des feuilles de ginkgo.
PCT/JP2015/059604 2014-03-29 2015-03-27 Composition inhibant la stéatose hépatique et la néphromégalie provoquées par le diabète et procédé de production de celle-ci WO2015152045A1 (fr)

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KR1020167030383A KR101873141B1 (ko) 2014-03-29 2015-03-27 당뇨병에 의한 지방간을 억제하기 위한 조성물 및 당뇨병에 의한 신장 비대를 억제하기 위한 조성물
CN201580017620.9A CN106470692B (zh) 2014-03-29 2015-03-27 抑制由糖尿病引起的脂肪肝和肾肥大的组合物及其制造方法
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KR102283127B1 (ko) * 2018-06-19 2021-07-29 주식회사 엠디헬스케어 류코노스톡속 균주를 포함하는 간 기능 개선용 조성물
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