WO2025010709A1 - 育亨宾药物在治疗2型糖尿病中的用途 - Google Patents

育亨宾药物在治疗2型糖尿病中的用途 Download PDF

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WO2025010709A1
WO2025010709A1 PCT/CN2023/107205 CN2023107205W WO2025010709A1 WO 2025010709 A1 WO2025010709 A1 WO 2025010709A1 CN 2023107205 W CN2023107205 W CN 2023107205W WO 2025010709 A1 WO2025010709 A1 WO 2025010709A1
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yohimbine
diabetes
drug
type
treatment
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陈祖昕
刘欣安
洪丰
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Shenzhen Institute of Advanced Technology of CAS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
    • 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
    • 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

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  • the invention belongs to the field of biomedical technology, and specifically relates to use of a yohimbine drug in treating type 2 diabetes.
  • Diabetes is one of the top five causes of death worldwide and one of the main causes of blindness, renal failure, lower limb amputation and other diseases worldwide.
  • type 2 diabetes which is directly related to obesity, has the largest number of patients and the most complicated treatment.
  • Type 2 diabetes is a chronic metabolic disease. Insulin resistance and pancreatic ⁇ -cell dysfunction are two important factors that cause type 2 diabetes.
  • the commonly used treatments for type 2 diabetes internationally include diet control, exercise, drug therapy and diabetes education.
  • drug therapy mainly includes insulin, oral biological and biochemical drugs, as well as comprehensive treatments such as antihypertensive, lipid-lowering, and anticoagulation.
  • drug therapy has certain functional differences in effectively controlling blood sugar, restoring ⁇ -cell mass, reducing or eliminating the need for insulin injections, and preventing or reversing the decline in ⁇ -cell function.
  • the therapeutic effect of drugs for treating type 2 diabetes mellitus is not obvious in reducing blood sugar, the patient has poor glucose tolerance, poor insulin tolerance, and high treatment cost.
  • the present invention provides a use of a yohimbine drug in treating type 2 diabetes.
  • the yohimbine medicine includes a yohimbine oral preparation and a yohimbine injection.
  • the yohimbe oral compound preparation includes yohimbe hydrochloride tablets, yohimbe sustained-release tablets, yohimbe sustained-release capsules, yohimbe enteric-coated tablets, yohimbe enteric-coated capsules, and yohimbe compound preparation.
  • the yohimbine drug achieves the effect of treating type 2 diabetes by lowering fasting blood sugar, glucose tolerance, and insulin tolerance of patients.
  • yohimbine significantly reduces fasting blood sugar, glucose tolerance, and insulin tolerance in diabetic patients, thereby achieving the effect of treating type 2 diabetes.
  • the dosage of the yohimbine drug for regulating blood sugar is 0.1 mg/kg-10 mg/kg.
  • the yohimbine drug regulates the insulin dosage to be 0.1 mg/kg-10 mg/kg.
  • An object of the present invention is to provide a method for treating type 2 diabetes.
  • the method of treating type 2 diabetes mellitus comprises administering to a subject the drug Yobconazole.
  • the yohimbine medicine includes yohimbine oral preparation and yohimbine injection.
  • the yohimbe oral compound preparation includes yohimbe hydrochloride tablets, yohimbe sustained-release tablets, yohimbe sustained-release capsules, yohimbe enteric-coated tablets, yohimbe enteric-coated capsules, and yohimbe compound preparation.
  • the dosage of the yohimbine drug for regulating blood sugar is 0.1 mg/kg to 10 mg/kg.
  • the yohimbine drug regulates the insulin dosage to be 0.1 mg/kg to 10 mg/kg.
  • the use of the yohimbine drug provided by the present invention in treating type 2 diabetes provides a new idea for treating type 2 diabetes.
  • the yohimbine drug has a wide source and is easy to prepare, which reduces the treatment cost of type 2 diabetes and has the effects of significantly lowering blood sugar, improving glucose tolerance and insulin resistance.
  • FIG1 is a diagram of the effects of different doses of yohimbine injection on the blood glucose level of normal mice on a free diet, as provided in Example 1;
  • FIG. 2 shows that Yohimbine injection significantly improves glucose tolerance in normal mice, as provided in Example 2;
  • FIG3 shows that the administration of yohimbine by injection significantly reduces the free diet blood glucose level of type 2 diabetic mice as provided in Example 3;
  • FIG4 shows that Yohimbine injection significantly improves glucose tolerance and insulin sensitivity in type 2 diabetic mice, as provided in Example 4.
  • FIG5 shows that oral administration of yohimbine significantly improves glucose tolerance and insulin sensitivity in type 2 diabetic mice, as provided in Example 5;
  • FIG. 6 provides a graph showing that chronic yohimbine injection significantly improves free-feed blood glucose levels in type 2 diabetic mice in Example 6.
  • Example 1 Using normal C57BL/6J mice to verify that yohimbine significantly reduces free-feed blood glucose levels
  • mice 8-10 week old C57BL/6J mice, fed a normal diet, totaling 20 mice.
  • the feeding and experimental procedures were in accordance with the guidelines for animal care and protection of the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences.
  • the experimental animals were purchased from Jicui Yaokang.
  • mice were divided into four groups, with 5 animals in each group. Each group was administered with normal saline, 0.5 mg/kg yohimbine, 1 mg/kg yohimbine, and 1.5 mg/kg yohimbine, respectively. The administration method was intraperitoneal injection, and the injection volume was 10 ml/kg.
  • Example 1 The experimental results of Example 1 are shown in Figure 1.
  • the black curve 1 shows that the blood sugar of normal mice remained within a certain range within 120 minutes after intraperitoneal injection of normal saline.
  • Yellow 2, blue 3 and red 4 respectively represent the blood sugar changes of normal mice after injection of 0.5 mg/kg, 1 mg/kg and 1.5 mg/kg yohimbine.
  • 1 mg/kg and 1.5 mg/kg yohimbine injections significantly reduced the free diet blood sugar levels of mice, while 0.5 mg/kg yohimbine injections did not produce significant changes in blood sugar levels.
  • Two-way RM ANOVA was used for inter-group comparison, *p ⁇ 0.05, ***p ⁇ 0.001, the horizontal axis represents time, and the vertical axis represents blood sugar value.
  • Example 2 Using normal C57BL/6J mice to verify that yohimbine can significantly improve blood sugar clearance
  • mice were divided into 2 groups, with 8-9 animals in each group. Each group was given normal saline and 1.5 mg/kg yohimbine injection. The administration method was intraperitoneal injection, and the injection volume was 10 ml/kg.
  • Example 2 The experimental results of Example 2 are shown in Figure 2.
  • the black curve 1 is a glucose tolerance test of normal mice 30 minutes after intraperitoneal injection of normal saline.
  • the red curve 2 is a glucose tolerance test of normal mice 30 minutes after intraperitoneal injection of 1.5 mg/kg yohimbine. It can be seen from the figure that compared with the normal saline group, yohimbine injection significantly reduced the fasting blood glucose level of mice; and it can significantly improve the blood glucose clearance ability after glucose injection.
  • Two-way RM ANOVA was used for inter-group comparison, **p ⁇ 0.05, ***p ⁇ 0.001, the horizontal axis represents time, and the vertical axis represents blood glucose value.
  • Example 3 Using a high-fat diet-induced type 2 diabetes mouse model to verify that yohimbine injection significantly reduces free-feed blood glucose levels
  • mice were divided into 2 groups, with 8-9 animals in each group. Each group was injected with normal saline and 1.5 mg/kg yohimbine respectively. The administration method was intraperitoneal injection, and the injection volume was 10 ml/kg.
  • Example 3 show that the injection of yohimbine significantly reduces the free diet blood glucose level of type 2 diabetes model mice.
  • the black curve 1 is the free diet blood glucose detection experiment of mice injected with normal saline
  • the red curve 2 is the free diet blood glucose detection experiment of mice injected with 10ml/kg yohimbine.
  • This experiment was conducted on type 2 diabetes model mice induced by a high-fat diet.
  • 1.5mg/kg yohimbine injection significantly reduced the free diet blood glucose level of type 2 diabetes mice.
  • the comparison between groups was performed using Two-way RM ANOVA, ****p ⁇ 0.001, the horizontal axis represents time, and the vertical axis represents blood glucose value.
  • Example 4 Using a high-fat diet-induced type 2 diabetes mouse model to verify that yohimbine injection significantly improves glucose tolerance and insulin sensitivity
  • mice were divided into 2 groups, with 8-9 animals in each group. Each group was injected with normal saline and 1.5 mg/kg yohimbine respectively. The administration method was intraperitoneal injection, and the injection volume was 10 ml/kg.
  • Glucose tolerance test The high-fat diet-induced type 2 diabetes model mice were tested after fasting for 16 hours. After measuring the fasting blood glucose level, normal saline and 1.5 mg/kg yohimbine were injected respectively. The blood glucose level was measured again 30 minutes later, and then 1.5 g/kg glucose was intraperitoneally injected and blood glucose changes were continuously monitored.
  • Example 4 The experimental results of Example 4 are shown in Figure 4, including that yohimbine injection significantly improved glucose tolerance and insulin sensitivity tests.
  • This experiment used high-fat diet-induced type 2 diabetes model mice for research.
  • Figure A compared with saline group 1, 1.5 mg/kg yohimbine injection significantly improved mouse glucose tolerance
  • Figure B compared with saline group 1, 1.5 mg/kg yohimbine injection significantly improved mouse insulin sensitivity.
  • the comparison between groups was performed using Two-way RM ANOVA, ****p ⁇ 0.001, the horizontal axis represents time, and the vertical axis represents blood glucose value.
  • yohimbine injection significantly reduced the fasting blood glucose level of type 2 diabetes model mice and significantly improved insulin sensitivity.
  • Example 5 Using a high-fat diet-induced type 2 diabetes mouse model to verify that oral administration of yohimbine significantly improves glucose tolerance and insulin sensitivity
  • the experimental animals were divided into 2 groups, with 8-9 animals in each group.
  • the physiological saline group and the 1.5 mg/kg yohimbine injection group were injected intraperitoneally with an injection volume of 10 ml/kg.
  • mice with type 2 diabetes induced by a high-fat diet were tested after fasting for 16 hours. After measuring the fasting blood glucose level, normal saline and 1.5 mg/kg yohimbine were gavaged orally, and the blood glucose level was measured again 30 minutes later. Subsequently, 1.5 g/kg glucose was intraperitoneally injected and blood glucose changes were continuously monitored.
  • Example 5 The experimental results of Example 5 are shown in Figure 5.
  • This experiment was conducted using type 2 diabetes model mice induced by a high-fat diet.
  • Figure A compared with saline group 1, 1.5 mg/kg yohimbine gavage significantly improved glucose tolerance in mice
  • Figure B compared with saline group 1, 1.5 mg/kg yohimbine gavage significantly improved insulin sensitivity in mice.
  • the comparison between the groups was performed using Two-way RM ANOVA, ****p ⁇ 0.001, the horizontal axis represents time, and the vertical axis represents blood glucose value.
  • Example 6 used a high-fat diet-induced type 2 diabetes mouse model to verify that chronic yohimbine injection significantly reduced free-feed blood glucose levels.
  • mice were divided into 2 groups, with 8-9 animals in each group. Each group was injected with normal saline and 1.5 mg/kg yohimbine respectively; the injections were continued for 14 days, and the blood glucose level was measured every day before the injection. The administration method was intraperitoneal injection, and the injection volume was 10 ml/kg. A glucose tolerance test was performed on the 15th day.
  • Glucose tolerance test The chronic injection type 2 diabetes model mice were tested after fasting for 16 hours. After measuring the fasting blood glucose level, 1.5 g/kg of glucose was intraperitoneally injected and the blood glucose changes were continuously monitored.
  • Example 6 The experimental results of Example 6 are shown in Figure 6.
  • This experiment was conducted using type 2 diabetes model mice induced by a high-fat diet.
  • Figure A compared with saline group 1, chronic 1.5 mg/kg yohimbine injection significantly increased the free diet blood glucose level of mice.
  • Figure B is the area under the curve data of Figure A.
  • Figure C shows the glucose tolerance experiment.
  • Figure D is the area under the curve data of Figure A.
  • the area under the glucose tolerance curve of the chronic yohimbine injection group was significantly lower than that of the control group, indicating that the glucose clearance ability of mice in the chronic yohimbine injection group was improved.
  • Figure A the comparison between groups was performed using Two-way RM ANOVA, ****p ⁇ 0.001, the horizontal axis represents time, and the vertical axis represents blood glucose value.
  • Figures B and D the comparison between groups was performed using T test.
  • mice in the chronic yohimbine administration group was significantly enhanced compared with that in the saline group.

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Abstract

育亨宾药物在治疗2型糖尿病中的用途。育亨宾药物通过降低糖尿病人的空腹血糖、降低耐糖量、降低耐胰岛素耐量达到治疗2型糖尿病的作用。

Description

育亨宾药物在治疗2型糖尿病中的用途 技术领域
本发明属于生物医疗技术领域，具体涉及一种育亨宾药物在治疗2型糖尿病中的用途。
背景技术
糖尿病是全球五大死因之一，也是导致全球失明、肾衰竭、下肢截肢等疾病的主要原因之一。在常见的三种糖尿病中，与肥胖直接相关的2型糖尿病人数最多，治疗最复杂。2型糖尿病是一种慢性代谢性疾病，胰岛素抵抗和胰岛β细胞功能减退是引发2型糖尿病的两个重要因素。目前，国际上常用的2型糖尿病治疗方法包括饮食控制、运动、药物治疗和糖尿病教育等方面。其中，药物治疗主要包括胰岛素、口服生物生化药物，以及降压、降脂、抗凝等综合治疗。但是，药物治疗在有效控制血糖、恢复β细胞质量、减少或消除注射胰岛素的需求、防止或逆转β细胞功能下降等方面均有一定功能差异性。
由于目前尚未有完全根治糖尿病的办法，控制血糖是糖尿病治疗的核心，但实际控制率也仅为5.78％。并且，治疗2型糖尿病大约花5-10万元，并且二型糖尿病目前还没有彻底治愈的办法，只能通过长期服用药物控制血糖，增大治疗成本。
现有技术中，药物治疗2型糖尿病的治疗效果中降低血糖不明显、耐糖量差、耐胰岛素耐量差、治疗成本高的问题。
发明内容
为了解决现有技术中，药物治疗2型糖尿病降低血糖不明显、耐糖量差、耐胰岛素耐量差、成本高的问题，本发明提供了一种育亨宾药物在治疗2型糖尿病中的用途。
进一步地，所述育亨宾药物包括育亨宾口服制剂和育亨宾注射液。
进一步地，所述育亨宾口服复方制剂包括盐酸育亨宾片、育亨宾缓释片、育亨宾缓释胶囊、育亨宾肠溶片、育亨宾肠溶胶囊、育亨宾复方制剂。
进一步地，所述育亨宾药物通过降低尿病人的空腹血糖、降低耐糖量、降低耐胰岛素耐量达到治疗2型糖尿病的作用。
进一步地，急性或慢性育亨宾给药显著降低糖尿病人的空腹血糖、降低耐糖量、降低耐胰岛素耐量达到治疗2型糖尿病的作用。
进一步地，所述育亨宾药物调控血糖的使用剂量为0.1mg/kg-10mg/kg。
进一步地，所述育亨宾药物调控胰岛素的剂量为0.1mg/kg-10mg/kg。
本发明的一个目的是提供一种治疗2型糖尿病的方法。
该治疗2型糖尿病的方法给受试者以育宾亨药物。
进一步地，所述育亨宾药物包括育亨宾口服制剂和亨宾注射液。
进一步地，所述育亨宾口服复方制剂包括盐酸育亨宾片、育亨宾缓释片、育亨宾缓释胶囊、育亨宾肠溶片、育亨宾肠溶胶囊、育亨宾复方制剂。
进一步地，所述育亨宾药物调控血糖的使用剂量为0.1mg/kg到10mg/kg。
进一步地，所述育亨宾药物调控胰岛素的剂量为0.1mg/kg到10mg/kg。
本发明提供的育亨宾药物在治疗2型糖尿病中的用途为治疗2型糖尿病提供了一条新的思路，育亨宾药物来源广泛、容易制取，降低了2型糖尿病的治疗成本，且具有明显降低血糖、耐糖量好、耐胰岛素耐量好的效果。
附图说明
图1为实施例1提供的是不同剂量育亨宾注射给药对正常小鼠自由饮食血糖水平的影响；
图2为实施例2提供的是育亨宾注射给药显著改善正常小鼠的葡萄糖耐受；
图3为实施例3提供的是育亨宾注射给药显著降低二型糖尿病小鼠的自由饮食血糖水平；
图4为实施例4提供的是育亨宾注射给药显著改善二型糖尿病小鼠的葡萄糖耐受和胰岛素敏感性；
图5为实施例5提供的是育亨宾灌胃给药显著改善二型糖尿病小鼠的葡萄糖耐受和胰岛素敏感性；
图6为实施例6提供的是慢性育亨宾注射显著改善二型糖尿病小鼠的自由饮食血糖水平。
具体实施方式
为了使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图对本发明的具体实施方式做详细的说明，但不能理解为对本发明的可实施范围的限定。
实施例1采用正常C57BL/6J小鼠验证育亨宾显著地降低自由饮食血糖水平
(1)实验动物。8-10周大C57BL/6J小鼠，正常饮食，共20只。饲养和实验过程遵守中国科学院深圳先进技术研究院动物管理与保护的准则。本实验动物购于集萃药康。
(2)实验分组和处理。实验动物分为四组，每组5只。分别每组给药生理盐水、0.5mg/kg育亨宾、1mg/kg育亨宾和1.5mg/kg育亨宾。采用腹腔注射给药方式，注射体积为10ml/kg。
(3)自由饮食血糖检测实验。小鼠正常饮食下进行剪尾取血，用拜耳血糖仪测定血糖浓度。
实施例1的实验结果如图1所示，图中，黑色曲线1为正常小鼠进行生理盐水腹腔注射后的120分钟内血糖保持在一定范围内变化。黄色2，蓝色3和红色4分别表示0.5mg/kg,1mg/kg和1.5mg/kg育亨宾注射后正常小鼠的血糖变化。与生理盐水组相比，1mg/kg和1.5mg/kg育亨宾注射显著降低小鼠的自由饮食血糖水平，而0.5mg/kg育亨宾注射对血糖水平并不产生显著性变化。组间比较采用Two-way RM ANOVA，*p<0.05，***p<0.001,横坐标表示时间，纵坐标表示血糖值。
结论：与生理盐水组相比，育亨宾的降血糖效果具有剂量依赖性。1mg/kg和1.5mg/kg育亨宾注射显著降低小鼠的自由饮食血糖水平，而0.5mg/kg育亨宾注射对血糖水平并不产生显著性变化。
实施例2采用正常C57BL/6J小鼠验证育亨宾可以显著地改善血糖清除能力
(1)实验动物。8-10周大C57BL/6J小鼠，正常饮食。饲养和实验过程遵守中国科学院深圳先进技术研究院动物管理与保护的准则。本实验动物购于集萃药康。
(2)实验分组和处理。实验动物分为2组，每组8-9只。分别每组给药生理盐水和1.5mg/kg育亨宾注射组。采用腹腔注射给药方式，注射体积为10ml/kg。
(3)葡萄糖耐受实验。正常C57BL/6J小鼠在禁食16小时后，进行测试。在测定空腹血糖水平后，分别注射生理盐水和1.5mg/kg育亨宾，30分钟后再次测定血糖水平，随后腹腔注射1.5g/kg葡萄糖并持续监测血糖变化。
实施例2实验结果如图2所示，图中，黑色曲线1为正常小鼠进行生理盐水腹腔注射30分钟后进行葡萄糖耐受测试。红色曲线2为正常小鼠进行1.5mg/kg育亨宾腹腔注射30分钟后进行葡萄糖耐受测试。图中可见，与生理盐水组相比，育亨宾注射显著降低小鼠的空腹血糖水平；并且能显著改善葡萄糖注射后的血糖清除能力。组间比较采用Two-way RM ANOVA，**p<0.05，***p<0.001,横坐标表示时间，纵坐标表示血糖值。
结论：与生理盐水组相比，育亨宾注射显著降低小鼠的空腹血糖水平，并且能显著改善葡萄糖注射后的血糖清除能力。
实施例3采用高脂饮食诱导的二型糖尿病小鼠模型验证育亨宾注射给药显著降低自由饮食血糖水平
(1)实验动物。8-10周大C57BL/6J小鼠，含60％脂肪饲料喂养3个月后，体重和基础血糖显著升高。饲养和实验过程遵守中国科学院深圳先进技术研究院动物管理与保护的准则。本实验动物购于集萃药康。
(2)实验分组和处理。实验动物分为2组，每组8-9只。分别每组注射生理盐水、1.5mg/kg育亨宾注射组。采用腹腔注射给药方式，注射体积为10ml/kg。
(3)自由饮食血糖检测实验。小鼠正常饮食下进行剪尾取血，用拜耳血糖仪测定血糖浓度。
实施例3实验结果显示，育亨宾注射给药显著降低二型糖尿病模型小鼠的自由饮食血糖水平，图中，黑色曲线1为注射生理盐水的小鼠的自由饮食血糖检测实验，红色曲线2为注射10ml/kg育亨宾的小鼠的自由饮食血糖检测实验。本实验采用高脂饮食诱导的二型糖尿病模型小鼠进行研究，如图中显示，与生理盐水组相比，1.5mg/kg育亨宾注射显著降低二型糖尿病小鼠的自由饮食血糖水平。组间的比较采用Two-way RM ANOVA，****p<0.001,横坐标表示时间，纵坐标表示血糖值。
结论：与生理盐水组相比，育亨宾注射给药显著降低自由饮食血糖水平。
实施例4采用高脂饮食诱导的二型糖尿病小鼠模型验证育亨宾注射给药显著改善葡萄糖耐受和胰岛素敏感性
(1)实验动物。8-10周大C57BL/6J小鼠，含60％脂肪饲料喂养3个月后，体重和基础血糖显著升高。饲养和实验过程遵守中国科学院深圳先进技术研究院动物管理与保护的准则。本实验动物购于集萃药康。
(2)实验分组和处理。实验动物分为2组，每组8-9只。分别每组注射生理盐水和1.5mg/kg育亨宾注射组。采用腹腔注射给药方式，注射体积为10ml/kg。
(3)葡萄糖耐受实验。高脂饮食诱导的二型糖尿病模型小鼠在禁食16小时后进行测试。在测定空腹血糖水平后，分别注射生理盐水和1.5mg/kg育亨宾，30分钟后再次测定血糖水平，随后腹腔注射1.5g/kg葡萄糖并持续监测血糖变化。
(4)胰岛素敏感性实验。高脂饮食诱导的二型糖尿病模型小鼠在禁食4小时后进行测试。在测定空腹血糖水平后，分别注射生理盐水和1.5mg/kg育亨宾，30分钟后再次测定血糖水平，随后腹腔注射1.5UI/kg胰岛素并持续监测血糖变化。
实施例4的实验结果显示在图4，包括亨宾注射给药显著改善葡萄糖耐受和胰岛素敏感性测试。本实验采用高脂饮食诱导的二型糖尿病模型小鼠进行研究，如图A中显示，与生理盐水组1相比，1.5mg/kg育亨宾注射显著改善小鼠葡萄糖耐受；如图B中显示，与生理盐水组1相比，1.5mg/kg育亨宾注射显著改善小鼠胰岛素敏感性。组间的比较采用Two-way RM ANOVA，****p<0.001,横坐标表示时间，纵坐标表示血糖值。
结论：与生理盐水组相比，育亨宾注射显著改善降低二型糖尿病模型小鼠在葡萄糖注射后的血糖清除能力。
与生理盐水组相比，育亨宾注射显著降低二型糖尿病模型小鼠的空腹血糖水平，并且能显著改善胰岛素敏感性。
实施例5采用高脂饮食诱导的二型糖尿病小鼠模型验证育亨宾灌胃给药显著改善葡萄糖耐受和胰岛素敏感性
(1)实验动物。8-10周大C57BL/6J小鼠，含60％脂肪饲料喂养3个月后，体重和基础血糖显著升高。饲养和实验过程遵守中国科学院深圳先进技术研究院动物管理与保护的准则。本实验动物购于集萃药康。
(2)实验分组和处理。实验动物分为2组，每组8-9只。生理盐水、1.5mg/kg育亨宾注射组。采用腹腔注射给药方式，注射体积为10ml/kg。
(3)葡萄糖耐受实验。高脂饮食诱导的二型糖尿病模型小鼠在禁食16小时后进行测试。在测定空腹血糖水平后，分别生理盐水灌胃和1.5mg/kg育亨宾灌胃，30分钟后再次测定血糖水平，随后腹腔注射1.5g/kg葡萄糖并持续监测血糖变化。
(4)胰岛素敏感性实验。高脂饮食诱导的二型糖尿病模型小鼠在禁食4小时后进行测试。在测定空腹血糖水平后，分别生理盐水灌胃和1.5mg/kg育亨宾灌胃，30分钟后再次测定血糖水平，随后腹腔注射1.5UI/kg胰岛素并持续监测血糖变化。
实施例5的实验结果显示在图5。本实验采用高脂饮食诱导的二型糖尿病模型小鼠进行研究，如图A中显示，与生理盐水组1相比，1.5mg/kg育亨宾灌胃给药显著改善小鼠葡萄糖耐受；如图B中显示，与生理盐水组1相比，1.5mg/kg育亨宾灌胃给药显著改善小鼠胰岛素敏感性。组间的比较采用Two-way RM ANOVA，****p<0.001,横坐标表示时间，纵坐标表示血糖值。
结论：结果显示，与生理盐水组相比，育亨宾灌胃给药显著降低二型糖尿病模型小鼠的空腹血糖水平，并且能显著改善葡萄糖注射后的血糖清除能力。
结果显示，与生理盐水组相比，育亨宾注射显著降低二型糖尿病模型小鼠的空腹血糖水平，并且能显著改善胰岛素敏感性。
实施例6采用高脂饮食诱导的二型糖尿病小鼠模型验证慢性育亨宾注射给药显著降低自由饮食血糖水平。
(1)实验动物。8-10周大C57BL/6J小鼠，含60％脂肪饲料喂养3个月后，体重和基础血糖显著升高。饲养和实验过程遵守中国科学院深圳先进技术研究院动物管理与保护的准则。本实验动物购于集萃药康。
(2)实验分组和处理。实验动物分为2组，每组8-9只。分别每组注射生理盐水、1.5mg/kg育亨宾注射组；分别连续注射14天，每天在注射前测定血糖水平。采用腹腔注射给药方式，注射体积为10ml/kg。在第15天进行葡萄糖耐受测试。
(3)自由饮食血糖检测实验。小鼠正常饮食下进行剪尾取血，用拜耳血糖仪测定血糖浓度。
(4)葡萄糖耐受实验。慢性注射二型糖尿病模型小鼠在禁食16小时后进行测试。在测定空腹血糖水平后，腹腔注射1.5g/kg葡萄糖并持续监测血糖变化。
实施例6的实验结果显示在图6。本实验采用高脂饮食诱导的二型糖尿病模型小鼠进行研究，如图A中显示，与生理盐水组1相比，慢性1.5mg/kg育亨宾注射给药显著小鼠的自由饮食血糖水平。图B为图A曲线下面积数据。图C显示的是葡萄糖耐受实验。图D为A图曲线下面积数据。慢性育亨宾注射组糖耐受曲线线下面积数值显著地低于对照组，这表明慢性育亨宾注射组小鼠葡萄糖清除能力得到改善。图A，组间的比较采用Two-way RM ANOVA，****p<0.001,横坐标表示时间，纵坐标表示血糖值。图B和D,组间比较采用T test。
结论：结果显示，与生理盐水组相比，慢性育亨宾注射显著降低自由饮食血糖水平。
结果显示，与生理盐水组相比，慢性育亨宾给药组小鼠葡萄糖清除能力显著增强。

Claims (12)

  1. 育亨宾药物在治疗2型糖尿病中的用途。
  2. 如权利要求1所述的育亨宾药物在治疗2型糖尿病中的用途，其特征在于，所述育亨宾药物包括育亨宾口服制剂和亨宾注射液。
  3. 如权利要求2所述的育亨宾药物在治疗2型糖尿病中的用途，其特征在于，所述育亨宾口服复方制剂包括盐酸育亨宾片、育亨宾缓释片、育亨宾缓释胶囊、育亨宾肠溶片、育亨宾肠溶胶囊、育亨宾复方制剂。
  4. 如权利要求1所述的育亨宾药物在治疗2型糖尿病中的用途，其特征在于，所述育亨宾药物通过降低糖尿病人的空腹血糖、降低耐糖量、降低耐胰岛素耐量达到治疗2型糖尿病的作用。
  5. 如权利要求1所述的育亨宾药物在治疗2型糖尿病中的用途，其特征在于，急性或慢性育亨宾给药显著降低糖尿病人的空腹血糖、降低耐糖量、降低耐胰岛素耐量达到治疗2型糖尿病的作用。
  6. 如权利要求1所述的育亨宾药物在治疗2型糖尿病中的用途，其特征在于，所述育亨宾药物调控血糖的使用剂量为0.1mg/kg到10mg/kg。
  7. 如权利要求1所述的育亨宾药物在治疗2型糖尿病中的用途，其特征在于，所述育亨宾药物调控胰岛素的剂量为0.1mg/kg到10mg/kg。
  8. 一种治疗2型糖尿病的方法，其特征在于，给受试者以育宾亨药物。
  9. 如权利要求7所述的治疗2型糖尿病的方法，其特征在于，所述育亨宾药物包括育亨宾口服制剂和亨宾注射液。
  10. 如权利要求8所述的治疗2型糖尿病的方法，其特征在于，所述育亨宾口服复方制剂包括盐酸育亨宾片、育亨宾缓释片、育亨宾缓释胶囊、育亨宾肠溶片、育亨宾肠溶胶囊、育亨宾复方制剂。
  11. 如权利要求7所述的治疗2型糖尿病的方法，其特征在于，所述育亨宾药物调控血糖的使用剂量为0.1mg/kg到10mg/kg。
  12. 如权利要求7所述的治疗2型糖尿病的方法，其特征在于，所述育亨宾药物调控胰岛素的剂量为0.1mg/kg到10mg/kg。
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Citations (1)

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JP2004065181A (ja) * 2002-08-08 2004-03-04 Japan Science & Technology Corp 糖尿病モデルマウス

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