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WO2017159912A1 - Composition fonctionnelle antidiabétique contenant du ramulus mori et de l'oxyresvératrol obtenus par extraction à l'eau chaude en tant qu'ingrédients actifs et son procédé de production - Google Patents

Composition fonctionnelle antidiabétique contenant du ramulus mori et de l'oxyresvératrol obtenus par extraction à l'eau chaude en tant qu'ingrédients actifs et son procédé de production Download PDF

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WO2017159912A1
WO2017159912A1 PCT/KR2016/003209 KR2016003209W WO2017159912A1 WO 2017159912 A1 WO2017159912 A1 WO 2017159912A1 KR 2016003209 W KR2016003209 W KR 2016003209W WO 2017159912 A1 WO2017159912 A1 WO 2017159912A1
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hot water
group
ort
extract
ethanol
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Korean (ko)
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최상원
김은정
안은영
전영희
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Industry Academic Cooperation Foundation of Daegu Catholic University
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Industry Academic Cooperation Foundation of Daegu Catholic University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • 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)
    • A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
    • A61K36/605—Morus (mulberry)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate

Definitions

  • the present invention relates to an antidiabetic functional composition containing a hot water extract and oxyresveratrol as an active ingredient, and more particularly, to a composition for preventing and treating diabetes by administering the upper extremity hot water extract and oxyresveratrol in Streptozotocin-induced diabetic rats. It is about.
  • Diabetes is on the rise all over the world, and in Korea, the incidence of metabolic diseases and cancer is gradually increasing due to westernized diet and lack of exercise. According to the 2013 Cause of Death Statistics conducted by the National Statistical Office, deaths due to diabetes rank 6th and 4th, respectively, and the deaths from complications are expected to account for a greater proportion of all deaths. In addition, according to the National Health and Nutrition Survey conducted by the Centers for Disease Control and Prevention in 2012, the prevalence of diabetes has increased by 2.4% over the last decade. Guariguata et al. Estimated that diabetes mellitus in Korea is expected to increase by 2.5% to 8.9% of Korea's total population in 2013 and 11.4% by 2035. Diabetes has already become a serious social and health problem in our society.
  • Diabetes is a metabolic disease caused by an absolute or relative lack of insulin and is divided into type 1 diabetes and type 2 diabetes depending on the cause of the onset.
  • Type 1 diabetes is a disease caused by the lack of insulin itself and can be divided into immunomediated and idiopathic. The destruction of pancreatic beta cells due to autoimmune reactions is called immunomediation, which accounts for 5-10% of all diabetes. Diabetes of unknown type 1 diabetes is idiopathic.
  • Type 1 diabetes requires the treatment of insulin and can be taken with oral hypoglycemic agents as needed.
  • Type 2 diabetes is a disease caused by increased resistance to insulin receptors or decreased insulin sensitivity. There are genetic factors, but it is combined with many environmental factors such as age, obesity, and decreased physical activity.
  • Diabetes is more problematic due to complications than the disease itself.
  • Acute complications of diabetes include hyperglycemic coma that leads to coma due to hyperglycemia, ketoacidosis due to overaccumulation of ketone acid, and blood sugar due to incorrect use of insulin or hypoglycemic agents.
  • the hypoglycemia that is too low can be mentioned largely.
  • Chronic complications include diabetic retinopathy, nephropathy, neuropathy, and foot problems caused by poor blood circulation due to hyperglycemia.
  • diabetes is a metabolic disease that increases the risk of cardiovascular complications because it causes abnormalities in lipid metabolism as well as glucose metabolism-related disorders caused by inadequate use of sugar.
  • Cardiovascular complications related to diabetes include hypertension, coronary artery disease, stroke, peripheral artery disease, cardiomyopathy, and heart failure.
  • oral hypoglycemic agents are used for type 2 diabetes.
  • Types of oral hypoglycemic agents include sulfonylureas, which stimulate insulin secretion and improve insulin resistance, dipeptidyl peptidase-4 (DPP-4) inhibitors that increase insulin secretion and inhibit glucagon secretion, and inhibit hepatic angiogenesis. Biguanides improve resistance, thiazolidinedione (TZD) decreases insulin resistance in peripheral tissues and liver, and ⁇ -glucosidase inhibitors that delay glucose absorption.
  • DPP-4 dipeptidyl peptidase-4
  • Biguanides improve resistance
  • thiazolidinedione (TZD) decreases insulin resistance in peripheral tissues and liver
  • ⁇ -glucosidase inhibitors that delay glucose absorption.
  • Oral hypoglycemic agents vary depending on the mechanism of action, so they are not determined according to the type of diabetes, but insulin and oral hypoglycemic agents, or oral hypoglycemic agents, are often used in combination with diabetes mellitus. .
  • the reasons for the development of diabetes vary, and many studies are being conducted to develop new drugs based on the etiology of each.
  • the development of drugs that can improve the complications is an important part of diabetes treatment.
  • the latent product refers to products related to mulberry trees, and includes silkworms, mulberry, upper leaves, upper limbs, and lettuce.
  • Latent products have long been known to be effective in various diseases including diabetes. It is recorded that the auditory effect is effective for diabetes, and the upper limb is effective for wind and diuresis, and the upper lobe is effective for body swelling.
  • the herbaceous wood has been reported to have an effect on diabetes in the upper lobe, upper and lower skin, mulberry, and Jambun, and the upper leaf, upper limb and Jambun are also reported to be effective in wind.
  • the leaves of the mulberry which have been reported to reduce fasting glucose and glycated hemoglobin concentrations and decreased intestinal disaccharide enzyme activity in STZ-induced diabetic rats.
  • TG concentration, T-CHO concentration, low density lipoprotein concentration and TBARS content were decreased, and high density lipoprotein cholesterol (HDL-CHO) concentration was reported.
  • oxyresveratrol derivatives (glycosides mulberroside A and aglycone oxyresveratrol), resveratrol, and 2-arylbenzofuran derivatives have recently been identified from the upper limbs. It has been reported as an anti-melanin, and an antioxidant component.
  • mulberroside A which is also present in the upper limbs, has been reported to have anti-diabetic effects in alloxan-induced diabetic rats.
  • the antidiabetic effect of the water extract of the upper limbs and mulberroside A the main component, has been reported, but most of the studies have revealed the antidiabetic effect in the type 2 diabetes model. There have been no studies on the antidiabetic efficacy and mechanism of oxyresveratrol in water extract and type 1 diabetes in type 1 diabetes model.
  • the present invention comprises the steps of extracting 200 g of dried upper limbs and 100 g of baekryepi and 1L of ionized water, most preferably in an ultrasonic extractor for 2 hours; Concentrating the extracted upper limb and lettuce extract under reduced pressure under reduced pressure to obtain an extract of the upper limb and lettuce extract;
  • the upper extremity hot water extract has an excellent effect of providing a pharmaceutical and food composition with superior antidiabetic efficacy when compared with the extract of hot water extract.
  • Figure 1 is a graph showing the HPLC results of the upper liquor hot water extract, baekryepi hot water extract and ORT.
  • Figure 2 is a schematic diagram showing the separation and purification method of the two functional indicators (ORT & ORTG) from the upper liquor ethanol extract according to the present invention.
  • Figure 3 is a schematic diagram showing the MT and MRB administration after the STZ administration to the induction of diabetes mellitus according to the present invention.
  • Figure 4 is a schematic diagram showing the ORTG, ORT and Met administration after STZ administration to experimental animals for diabetes induction according to the present invention.
  • Figure 5 is a graph showing the fasting blood glucose measurement of the diabetes-induced experimental animal according to the present invention.
  • Figure 6 is a graph showing the measurement of plasma glucose and insulin content of the diabetes-induced experimental animals according to the present invention.
  • Figure 7 is a graph showing the change in lipid metabolism according to the administration of hot water extracts to the diabetes-induced experimental animals according to the present invention.
  • FIG. 8 is a graph showing triglyceride content after administration of hot water extracts of the upper limbs to a diabetic-induced experimental animal according to the present invention.
  • FIG. 9 is a graph showing the measured value of free fatty acid content after administration of hot water extracts of the upper limbs to the diabetic-induced experimental animal according to the present invention.
  • FIG. 10 is a graph showing changes in triglyceride and lipid metabolism in liver tissues after administration of hot water extracts of the upper limbs to a diabetic-induced experimental animal according to the present invention.
  • Figure 11 is a graph showing the results of measuring the disaccharide enzyme activity of the small intestine mucosa after administration of hot water extracts to the diabetes-induced experimental animals according to the present invention.
  • FIG. 12 is a graph showing the measured blood fasting glucose levels after administration of ORT, which is an indicator of the upper limbs, in the diabetes-induced experimental animal according to the present invention.
  • Figure 13 is a graph showing the measured value of plasma glucose and insulin content after ORT administration to the diabetic animal-derived experimental animal according to the present invention.
  • Figure 14 is a graph showing the change in lipid metabolism after administration of ORT to the diabetes-induced experimental animals according to the present invention.
  • 15 is a graph showing the measured value of free fatty acid content in plasma after ORT administration to a diabetic animal-derived experimental animal according to the present invention.
  • Figure 16 is a graph showing the disaccharide enzyme activity of the small intestine mucosa after the ORT administration to the diabetic induced animal according to the present invention.
  • Figure 17 is a graph showing the measurement value of liver tissue GLUT2 mRNA expression after ORT administration to the diabetes-induced experimental animals according to the present invention.
  • Figure 18 is a graph showing the measurement value of liver tissue glycogen content after ORT administration to a diabetic-induced experimental animal according to the present invention.
  • Figure 19 is a schematic diagram showing the effect of inhibiting diabetes appeared when the hot water extract and ORT administration in accordance with the present invention.
  • the present invention relates to a pharmaceutical and food composition for preventing and treating diabetes containing the upper limb hydrothermal extract and ORT as an active ingredient.
  • the upper limb hydrothermal extract has a content of mulberroside A and ORT 2 to 3 times higher than that of the hot birch extract.
  • the upper limb hydrothermal extract has a higher ORT content than the hot water extract, but the content of ORTG is very low [upper lichen hydrothermal extract: ORTG (2.45 ⁇ 0.06%), ORT (0.92 ⁇ 0.02%); Lepidoptera hot water extract: ORTG (19.71 ⁇ 2.80%), ORT (0.04 ⁇ 0.01%)]
  • the present invention relates to a pharmaceutical composition and a food composition characterized by superior antidiabetic effect when the upper limb hydrothermal extract and ORT administered as an index component thereof are higher than hot water extract in diabetic-induced mice using STZ.
  • the upper limb extract of the present invention may be extracted by a hydrophilic organic solvent such as water, ethanol, methanol, or a mixed solvent thereof, most preferably a hot water extract extracted using hot water.
  • a hydrophilic organic solvent such as water, ethanol, methanol, or a mixed solvent thereof, most preferably a hot water extract extracted using hot water.
  • ORT of the present invention is most preferably separated by EtOAC when separated from the hot water extract.
  • the food composition according to the present invention provides a food composition, characterized in that the formulation of any one of beverage, gum, tea, and wire.
  • composition according to the present invention is a pharmaceutical composition characterized in that it has any one formulation selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, emulsions, syrups, non-aqueous solvents, suspensions and lyophilized preparations. To provide.
  • compositions of the present invention may be prepared in the form of pharmaceutical compositions and may further comprise one or more non-toxic and pharmaceutically acceptable carriers, excipients, adjuvants or diluents or other active ingredients.
  • the upper limbs and limbs of the present invention are usually commercially available.
  • the numerical value of the upper limb hydrothermal extract or ORT content is limited to 1% by weight, but may be added up to 0.5 to 2.5% by weight.
  • the upper limbs were dried for one week after harvesting from mulberry trees without leaves in spring and then dried in a hot air dryer (COBP-15S, Sjunheung dryer, Boryyeong, Korea) below 50 ° C.
  • COBP-15S hot air dryer
  • the upper limbs were extracted twice with an 80% ethanol solution using an ultrasonic extractor, and filtered and concentrated under reduced pressure.
  • the degreased ethanol extract concentrated in the above step was dissolved in water, and then fractionated sequentially using CH 2 Cl 2, EtOAC, and n-BuOH solvent.
  • the upper limbs and epithelium hot water extracts (1 g) were diluted with 100 mL of distilled water, filtered through a 0.45 ⁇ m filter, and then injected into 10 ⁇ l of HPLC, where HPLC analysis was performed using Waters e2690.5 HPLC high performance liquid chromatography, column. ; YMC-Pack Pro C18, Solvent A (0.05% H3PO4 in H2O), Solvent B (CH3CN), flow rate; It was performed at 0.8 mL / min conditions.
  • the two functional indicators ORT and ORTG of the upper limbs and epithelium hot water extracts measured by HPLC were analyzed in comparison with the retention time of the standard, and the contents of the two extracts were calculated from the calibration curves of the two standard.
  • the experimental animals used for the antidiabetic effect of the upper limbs and epithelial hot water extract were male and 6-week-old ICR mice weighing 29 ⁇ 0.2 g and fed solid feed for 1 week and adapted to the experimental environment.
  • the experimental animals were 10 normal controls (NC), 10 diabees control (DC), 10 upper limbs (Mulberry twig (MT)) administered with the upper limbs hot water extract, and an epithelial diabetic group treated with hot water extract. (Mulberry root bark, MRB) was divided into 10 numbers.
  • the normal control group and the diabetic control group were treated with sterile saline, the upper limb diabetic group was administered with a concentration of 5 g / kg of the upper extremity hot water extract, and the epithelial diabetic group was administered with an epithelial hot water extract at 600 mg / kg.
  • the experimental animals used for the antidiabetic effect of the upper limb markers were male and 6 week old ICR mice weighing 33 ⁇ 0.3 g.
  • the experimental animals were 7 normal controls (NC) administered sterile saline, 7 diabetic controls (DC) administered sterile saline, 10 diabetic groups administered ORTG at a concentration of 600 mg / kg,
  • NC normal controls
  • DC diabetic controls
  • the experiment was divided into 10 diabetic groups administered ORT at a concentration of 600 mg / kg and 10 diabetic groups (Metformin, Met) administered at a concentration of 600 mg / kg.
  • STZ was dissolved in 0.1M citrate buffer (pH 4.5) and injected into the abdominal cavity at a constant time for 5 days at a dose of 50 mg / kg / day.
  • blood was collected from the vein of the vein to check the blood glucose to confirm the induction of diabetes.
  • the test animal was confirmed to be induced diabetes orally oral administration of upper extremity hot water extract 5g / kg to the upper extremity diabetic group (MT) for 15 days from the start of the experiment 16 days or 6g / kg oral administration of hot water extract to the epithelial diabetic group (MRB) (Fig. 3).
  • animals were sacrificed and blood, liver, soleus muscle, epididymal fat and small intestine were collected and used for sample analysis.
  • Example 2 In order to confirm the antidiabetic effect of the upper extremity indicator component, the experimental animals of Example 2 were intraperitoneally injected with STZ at a dose of 40 mg / kg / day for 5 days. Confirmed. Experimental animals confirming the blood glucose level of the above step was orally administered with ORTG, ORT and Met at a concentration of 0.6 g / kg, respectively, for 18 days after the start of the experiment (Fig. 4). Animals were sacrificed after sample administration and blood, liver, pancreas and small intestine were collected and used for sample analysis.
  • body weight was reduced in three groups of DC, MT, and MRB which induced diabetes compared to NC group.
  • the animals were fasted for 12 hours 10 days after the administration of the test sample, and fasting blood glucose was measured before the test sample was administered the next morning.
  • Glucose was measured using a blood glucose monitoring kit (ARRKRAY) with a small amount of blood taken from the vein.
  • the blood glucose measured in plasma after sacrifice of experimental animals was increased in the DC group and the MT group in the MT group compared to the NC group, but there was no significant difference in the MRB group.
  • Plasma insulin concentration showed a significant decrease only in the MT group compared to the NC group.
  • Plasma lipid concentration was measured using the plasma obtained in Example 5 to measure blood glucose and blood insulin concentrations following the administration of the upper limbs and epithelium hot water extract. Asan kit was used for glucose measurement. Plasma insulin was measured using a mouse Insulin ELISA kit (U-type, Shibayagi Co.).
  • the total cholesterol (T-CHO) concentrations of the MT and MRB groups were reduced by 72% and 73%, respectively, and the HDL-cholesterol (HDL-CHO) concentrations were not different between the experimental groups.
  • the HDL-CHO / T-CHO ratio was 80% lower in the DC group than the NC group, and 135% and 130% in the MT and MRB groups, respectively.
  • MT group showed lower T-CHO concentration and HDL-CHO / T-CHO ratio compared to DC group in MRB group.
  • triglyceride (TG) content in plasma was reduced in the DC group compared to the NC group and increased in the MT group compared to the DC group.
  • TG, T-CHO and FFA concentrations were measured using liver tissue obtained by the method of Example 5 to determine TG and T-CHO concentrations in the liver following administration of the upper limbs and epithelial hot water extract.
  • the liver TG concentration was measured to be 9.5% in the NC group, 19.4 in the DC group, 8.5 in the MT group, and 22.5 mg / g in the MRB group.
  • MT group decreased to normal level by 44%.
  • the liver T-CHO concentrations were 2.6 in the NC group, 2.9 in the DC group, 2.5 in the MT group, and 1.9 mg / g in the MRB group.
  • the DC group increased compared to the NC group and the MT and MRB groups decreased compared to the DC group. There was no significant difference.
  • the FFA content was decreased in the DC, MT and MRB groups compared to the NC group, and there was no difference between the three groups.
  • MT group had no effect on liver FFA level compared to DC group, but decreased TG concentration to normal level and decreased T-CHO level to improve liver lipid level.
  • Lactase, sucrase and maltase activity of small intestinal mucosa using the small intestine obtained in Example 5 to determine whether the hypoglycemic effect of MT group according to the administration of the upper limb and epithelium hot water extract was different was measured by Dahlqvist's method.
  • 0.1 mL of diluted enzyme samples (lactase: 1x, sucrase: 8x, maltase: 10x), substrate solution 0.056M disaccahride solution and 0.1mL 0.1M sodium maltase buffer (pH 6.0) were added to the test tube and mixed well. After reacting in a water bath for 1 hour, 0.8 mL of distilled water was added, soaked in water for 2 minutes, and the absorbance was measured at 420 nm.
  • the lactase activity of proximal was 70% decreased in the MT group compared to the DC group.
  • Sucrase activity was increased by 120% in DC group and 67% and 75% in MT and MRB groups, respectively.
  • Maltase activity was increased by 138% in DC group and 77% in MT group.
  • the MRB group was 70% less than the DC group.
  • lactase and sucrase activity was decreased in DC, MT and MRB groups compared to NC group.
  • lactase, sucrase and maltase activities were decreased in DC, MT and MRB groups compared to NC group.
  • the animals fasted 12 hours after 19 days of administration of the test sample, and fasting blood glucose was measured before administration of the test sample the next morning.
  • Glucose was measured using a blood glucose monitoring kit (ARRKRAY) with a small amount of blood taken from the vein.
  • fasting blood glucose was increased by 232% in the DC group compared to the NC group after 19 days of oral administration, and decreased in the ORTG group, the ORT group, and the Met group compared to the DC group.
  • the blood glucose measured in plasma after sacrifice of experimental animals was increased in the DC group compared to the NC group and decreased by 43% in the ORT group compared to the DC group. There was no significant difference between ORTG group and Met group. Plasma insulin concentrations were significantly decreased in the DC, ORT, ORTG, and Met groups that induced diabetes compared to the NC group, and there was no difference between the four groups. Therefore, it was shown that the change in blood glucose level of each group was not due to the change in insulin concentration.
  • Plasma lipid concentration was measured by using the plasma obtained in Example 5 to measure blood lipid concentrations according to the administration of the upper limb index component, and a glucose measuring solution (Asan kit) was used to measure plasma glucose content. Plasma insulin was measured using a mouse Insulin ELISA kit (U-type, Shibayagi Co.).
  • the plasma TG concentration and the GDL-CHO concentration did not differ between the experimental groups.
  • T-CHO concentration was decreased in ORTG, ORT and Met groups compared to DC group, and there was no difference between NC and DC groups.
  • the HDL-CHO / T-CHO ratio was significantly increased in the Met group compared to the other experimental groups.
  • 0.1 mL of diluted enzyme samples (lactase: 1x, sucrase: 8x, maltase: 10x), substrate solution 0.056M disaccahride solution and 0.1mL 0.1M sodium maltase buffer (pH 6.0) were added to the test tube and mixed well. After reacting in a water bath for 1 hour, 0.8 mL of distilled water was added, soaked in water for 2 minutes, and the absorbance was measured at 420 nm. Since the disaccharide dehydrogenase activity effect was shown only in the proximal part in the results of Experimental Example 5, only the proximal part was measured for disaccharide dehydrogenase activity.
  • mRNA expression level of glucose transporter glucose transporter 2 was measured using liver tissue obtained by the method of Example 5.
  • liver tissue was homogenized in a mortar containing liquid nitrogen and 1 mL of RNAiso Plus (TaKaRa) was added per 0.1 g of colon tissue. The supernatant was taken and chloroform 200uL was added and centrifuged at 4 ° C. and 10,000 rpm for 5 minutes. After isopropanol 500uL was added to the supernatant obtained by centrifugation, RNA pellet was obtained by centrifugation at 4 ° C and 14,000 rpm for 20 minutes. The RNA pellet obtained in the above step was washed with 75% ethanol, centrifuged at 4 ° C. and 9,500 rpm for 5 minutes and then air-dryed and dissolved in diethyl pyrocarbonate (DEPC) -treated water for analysis.
  • DEPC diethyl pyrocarbonate
  • upper limb hydrothermal extracts inhibited the activity of small intestinal disaccharides, lowering blood glucose, reducing plasma T-CHO levels, and reducing liver tissue TG levels, resulting in lipid-improving effects and superior efficacy compared to epithelial hot water extracts.
  • the antidiabetic effect of the upper limb markers confirmed the hypoglycemic effect of ORT, the major substance in the upper limb.
  • the mechanism of ORT increased the expression of GLUT2 mRNA in liver tissue, which increased glucose inflow into liver tissue and the synthesis of glycogen. It has been shown to increase blood sugar levels. It is also effective in improving lipids by reducing plasma T-CHO concentration (Fig. 19).
  • the present invention is a very useful invention for the health food and pharmaceutical industry because it has an excellent effect of providing a composition for the prevention and treatment of diabetes containing the upper limbs hot water extract and the upper limb index ORT.

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Abstract

La présente invention concerne une composition antidiabétique contenant du Ramulus Mori et de l'ORT obtenus par extraction à l'eau chaude, l'ORT étant un composant indicateur de Ramulus Mori. Lorsqu'elle est administrée à des rats diabétiques induits par streptozotocine, il a été confirmé que la composition antidiabétique de la présente invention est plus efficace en ce qui concerne l'inhibition de l'activité des disaccharidases dans l'intestin grêle pour abaisser le taux de glucose dans le sang et améliorer le lipide plasmatique, par rapport du Mori Cortex Radicis obtenu par extraction à l'eau chaude, et que la composition antidiabétique de la présente invention a un effet hypoglycémique en augmentant l'absorption du glucose dans les tissus hépatiques et en augmentant la synthèse de glycogène. Par conséquent, la composition antidiabétique de la présente invention a un excellent effet qui permet de l'utiliser en tant que médicament fonctionnel préventif et thérapeutique contre le diabète et en tant que composition alimentaire contenant du Ramulus Mori et de l'ORT obtenus par extraction à l'eau chaude, l'ORT étant un composant indicateur de Ramulus Mori.
PCT/KR2016/003209 2016-03-17 2016-03-29 Composition fonctionnelle antidiabétique contenant du ramulus mori et de l'oxyresvératrol obtenus par extraction à l'eau chaude en tant qu'ingrédients actifs et son procédé de production Ceased WO2017159912A1 (fr)

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KR1020160031775A KR101908772B1 (ko) 2016-03-17 2016-03-17 상지 열수추출물과 oxyresveratrol을 유효성분으로 함유하는 항당뇨 기능성 조성물 및 그 제조방법
KR10-2016-0031775 2016-03-17

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CN108403729B (zh) * 2018-05-14 2021-09-14 广东省微生物研究所（广东省微生物分析检测中心） 茶树菇提取物的制备方法及其在制备降尿酸药物的应用
KR102275824B1 (ko) 2021-01-22 2021-07-09 주식회사 리우에이치 당뇨 예방 및 개선용 복합 천연물 조성물 및 이의 제조 방법

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