Use of yohimbine drug in treatment of type 2 diabetes

Abstract

The use of yohimbine drug in the treatment of type 2 diabetes. The yohimbine drug achieves the effect of treating type 2 diabetes by reducing the fasting blood glucose, reducing the glucose tolerance and reducing the insulin resistance in patients with diabetes.

Description

Use of Yohimbine in the Treatment of Type 2 Diabetes Technical Field

[0001] The present invention belongs to the field of biomedical technology, and particularly relates to use of a yohimbine drug in treating type 2 diabetes. Background Art

[0002] Diabetes is one of the top five causes of death worldwide and a leading cause of blindness, kidney failure, lower limb amputations, and other diseases worldwide. Of the three common types of diabetes, type 2 diabetes, directly related to obesity, affects the largest number of people and is the most complex to treat. Type 2 diabetes is a chronic metabolic disease in which insulin resistance and decreased pancreatic beta-cell function are two key factors. Currently, commonly used treatments for type 2 diabetes internationally include diet control, exercise, medication, and diabetes education. Medication therapy primarily includes insulin, oral biochemical drugs, and comprehensive therapies such as antihypertensive, lipid-lowering, and anticoagulant treatments. However, medications vary in their effectiveness in controlling blood sugar, restoring beta-cell mass, reducing or eliminating the need for insulin injections, and preventing or reversing decreased beta-cell function.

[0003] Since there's currently no cure for diabetes, controlling blood sugar is the core of diabetes treatment, but the actual control rate is only 5.78%. Furthermore, treating type 2 diabetes costs approximately 50,000 to 100,000 yuan, and there's currently no cure for type 2 diabetes. Long-term medication is the only way to control blood sugar, increasing treatment costs.

[0004] In the prior art, drugs used to treat type 2 diabetes have the following problems: ineffective blood sugar reduction, poor glucose tolerance, poor insulin tolerance, and high treatment costs.

[0005] Summary of the Invention

[0006] In order to solve the problems in the prior art that drugs for treating type 2 diabetes do not significantly reduce blood sugar, have poor glucose tolerance, poor insulin tolerance, and are costly, the present invention provides a use of yohimbine in treating type 2 diabetes.

[0007] Furthermore, the yohimbine medicine includes yohimbine oral preparation and yohimbine injection.

[0008] Furthermore, 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.

[0009] Furthermore, the yohimbine drug achieves the effect of treating type 2 diabetes by lowering fasting blood sugar, glucose tolerance, and insulin tolerance of patients.

[0010] Furthermore, acute or chronic administration of yohimbine significantly reduces fasting blood sugar, glucose tolerance, and insulin tolerance in diabetic patients, thereby achieving the effect of treating type 2 diabetes.

[0011] Furthermore, the dosage of the yohimbine drug for regulating blood sugar is 0.1 mg / kg-10 mg / kg.

[0012] Furthermore, the dosage of the yohimbine drug for regulating insulin is 0.1 mg / kg-10 mg / kg.

[0013] An object of the present invention is to provide a method for treating type 2 diabetes.

[0014] The method of treating type 2 diabetes mellitus comprises administering the drug Yobconazole to a subject.

[0015] Furthermore, the yohimbine medicine includes yohimbine oral preparation and yohimbine injection.

[0016] Furthermore, 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.

[0017] Furthermore, the dosage of the yohimbine drug for regulating blood sugar is 0.1 mg / kg to 10 mg / kg.

[0018] Furthermore, the yohimbine drug regulates the insulin dosage to be 0.1 mg / kg to 10 mg / kg.

[0019] 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 cost of treating type 2 diabetes. It also has the effects of significantly lowering blood sugar, improving glucose tolerance, and improving insulin resistance. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] FIG1 shows the effects of different doses of yohimbine injection on the blood glucose levels of normal mice fed a free diet, as provided in Example 1;

[0021] FIG2 shows that Yohimbine injection significantly improves glucose tolerance in normal mice, as provided in Example 2;

[0022] FIG3 shows that Yohimbine injection significantly reduces the free-feeding blood glucose level in type 2 diabetic mice, as provided in Example 3;

[0023] FIG4 shows that Yohimbine injection significantly improves glucose tolerance and insulin sensitivity in type 2 diabetic mice, as provided in Example 4;

[0024] FIG5 shows that oral administration of yohimbine significantly improves glucose tolerance and insulin sensitivity in type 2 diabetic mice, as provided in Example 5;

[0025] FIG6 shows that chronic yohimbine injection significantly improves free-feeding blood glucose levels in type 2 diabetic mice, as provided in Example 6. DETAILED DESCRIPTION

[0026] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below with reference to the accompanying drawings, but they should not be understood as limiting the scope of implementation of the present invention.

[0027] Example 1: Using normal C57BL / 6J mice to verify that yohimbine significantly reduces free-feeding blood glucose levels

[0028] (1) Experimental animals. Twenty 8-10 week-old C57BL / 6J mice were fed a normal diet. The animal husbandry and experimental procedures adhered to 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.

[0029] (2) Experimental Grouping and Treatment. The experimental animals were divided into four groups, each with 5 animals. Each group was administered with normal saline, 0.5 mg / kg yohimbine, 1 mg / kg yohimbine, and 1.5 mg / kg yohimbine, respectively. The drug was administered by intraperitoneal injection with an injection volume of 10 ml / kg.

[0030] (3) Free-diet blood glucose test: Mice were tail-clipped and blood was collected while on a normal diet. Blood glucose levels were measured using a Bayer blood glucose meter.

[0031] The experimental result of embodiment 1 is as shown in Figure 1. Among the figures, black curve 1 is that normal mice carry out blood sugar and keep changing within a certain range within 120 minutes after intraperitoneal injection of normal saline.Yellow 2, blue 3 and red 4 represent the blood sugar change of normal mice after 0.5mg / kg, 1mg / kg and 1.5mg / kg Yohimbine injection respectively.Compared with the normal saline group, 1mg / kg and 1.5mg / kg Yohimbine injection significantly reduce the free diet blood sugar level of mice, while 0.5mg / kg Yohimbine injection does not produce significant change to blood sugar level.Two-way RM ANOVA is adopted for comparison between groups, *p<0.05, ***p<0.001, horizontal axis represents time, and vertical axis represents blood sugar level.

[0032] Conclusion: Compared with the saline group, the hypoglycemic effect of yohimbine was dose-dependent. Injections of 1 mg / kg and 1.5 mg / kg yohimbine significantly reduced the free-feeding blood glucose level of mice, while injection of 0.5 mg / kg yohimbine did not produce a significant change in blood glucose level.

[0033] Example 2: Using normal C57BL / 6J mice to verify that yohimbine can significantly improve blood sugar clearance

[0034] (1) Experimental animals. 8-10 week-old C57BL / 6J mice were fed a normal diet. Animal husbandry and experimental procedures adhered to the guidelines for animal care and protection of the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. These experimental animals were purchased from Jicui Yaokang.

[0035] (2) Experimental Grouping and Treatment. Experimental animals were divided into two groups, each with 8-9 animals. Each group was administered with normal saline or 1.5 mg / kg yohimbine. Administration was by intraperitoneal injection with an injection volume of 10 ml / kg.

[0036] (3) Glucose tolerance test. Normal C57BL / 6J mice were fasted for 16 hours before undergoing the test. After measuring fasting blood glucose levels, normal saline and 1.5 mg / kg yohimbine were injected, respectively. Blood glucose levels were measured again 30 minutes later. Subsequently, 1.5 g / kg glucose was intraperitoneally injected, and blood glucose levels were continuously monitored.

[0037] The experimental results of Example 2 are shown in Figure 2. In the figure, the black curve 1 is a glucose tolerance test performed on normal mice 30 minutes after intraperitoneal injection of normal saline. The red curve 2 is a glucose tolerance test performed on normal mice 30 minutes after intraperitoneal injection of 1.5 mg / kg yohimbine. As can be seen in the figure, compared with the normal saline group, yohimbine injection significantly reduced the fasting blood glucose levels 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 level.

[0038] Conclusion: Compared with the saline group, yohimbine injection significantly reduced the fasting blood glucose level of mice and significantly improved the blood glucose clearance ability after glucose injection.

[0039] Example 3: Using a high-fat diet-induced type 2 diabetes mouse model, it was verified that yohimbine injection significantly reduced free-feed blood glucose levels.

[0040] (1) Experimental Animals. 8-10 week old C57BL / 6J mice were fed a 60% fat diet for 3 months, and their body weight and basal blood glucose levels increased significantly. Animal husbandry and experimental procedures adhered to the guidelines for animal care and protection of the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. These experimental animals were purchased from Jicui Yaokang.

[0041] (2) Experimental Grouping and Treatment. Experimental animals were divided into two groups, each with 8-9 animals. Each group was injected with normal saline and 1.5 mg / kg yohimbine. Administration was by intraperitoneal injection with an injection volume of 10 ml / kg.

[0042] (3) Free-diet blood glucose test: Mice were tail-clipped and blood was collected while on a normal diet. Blood glucose levels were measured using a Bayer blood glucose meter.

[0043] Example 3 Experimental results show that Yohimbine injection significantly reduces the free diet blood glucose level of type 2 diabetes model mice. In the figure, black curve 1 is the free diet blood glucose detection experiment of mice injected with normal saline, and red curve 2 is the free diet blood glucose detection experiment of mice injected with 10ml / kg Yohimbine. This experiment uses type 2 diabetes model mice induced by a high-fat diet to study. As shown in the figure, compared with the normal saline group, 1.5mg / kg Yohimbine injection significantly reduces the free diet blood glucose level of type 2 diabetes mice. Comparison between groups adopts Two-way RM ANOVA, ****p<0.001, the horizontal axis represents time, and the vertical axis represents blood glucose value.

[0044] Conclusion: Yohimbine injection significantly reduced free-feeding blood glucose levels compared with the saline group.

[0045] Example 4: Using a high-fat diet-induced type 2 diabetes mouse model, it was verified that yohimbine injection significantly improved glucose tolerance and insulin sensitivity.

[0046] (1) Experimental Animals. 8-10 week old C57BL / 6J mice were fed a 60% fat diet for 3 months, and their body weight and basal blood glucose levels increased significantly. Animal husbandry and experimental procedures adhered to the guidelines for animal care and protection of the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. These experimental animals were purchased from Jicui Yaokang.

[0047] (2) Experimental Grouping and Treatment. Experimental animals were divided into two groups, each with 8-9 animals. Each group was injected with normal saline and 1.5 mg / kg yohimbine. Administration was by intraperitoneal injection with an injection volume of 10 ml / kg.

[0048] (3) Glucose tolerance test. Mice with a high-fat diet-induced type 2 diabetes model were tested after a 16-hour fast. After measuring fasting blood glucose levels, normal saline and 1.5 mg / kg yohimbine were injected, respectively. Blood glucose levels were measured again 30 minutes later. Subsequently, 1.5 g / kg glucose was intraperitoneally injected, and blood glucose levels were continuously monitored.

[0049] (4) Insulin sensitivity test. Mice with a high-fat diet-induced type 2 diabetes model were tested after a 4-hour fast. After measuring fasting blood glucose levels, normal saline and 1.5 mg / kg yohimbine were injected, respectively. Blood glucose levels were measured again 30 minutes later. Subsequently, 1.5 UI / kg of insulin was intraperitoneally injected, and blood glucose levels were continuously monitored.

[0050] 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 was conducted using mice with a high-fat diet-induced type 2 diabetes model. As shown in Figure A, compared with the saline group 1, 1.5 mg / kg yohimbine injection significantly improved glucose tolerance in mice; as shown in Figure B, compared with the saline group 1, 1.5 mg / kg yohimbine injection significantly improved insulin sensitivity in mice. The groups were compared using a two-way RM ANOVA, ****p<0.001, with the horizontal axis representing time and the vertical axis representing blood glucose levels.

[0051] Conclusion: Compared with the saline group, yohimbine injection significantly improved the blood glucose clearance ability of type 2 diabetic model mice after glucose injection.

[0052] Compared with the saline group, yohimbine injection significantly reduced the fasting blood glucose level of type 2 diabetes model mice and significantly improved insulin sensitivity.

[0053] Example 5: Using a high-fat diet-induced type 2 diabetes mouse model, it was verified that oral administration of yohimbine significantly improved glucose tolerance and insulin sensitivity.

[0054] (1) Experimental Animals. 8-10 week old C57BL / 6J mice were fed a 60% fat diet for 3 months, and their body weight and basal blood glucose levels increased significantly. Animal husbandry and experimental procedures adhered to the guidelines for animal care and protection of the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. These experimental animals were purchased from Jicui Yaokang.

[0055] (2) Experimental Grouping and Treatment. Experimental animals were divided into two groups, with 8-9 animals in each group. The saline group and the 1.5 mg / kg yohimbine injection group were administered by intraperitoneal injection with an injection volume of 10 ml / kg.

[0056] (3) Glucose tolerance test. Mice with a high-fat diet-induced type 2 diabetes model were tested after a 16-hour fast. After measuring fasting blood glucose levels, mice were gavaged with saline and 1.5 mg / kg yohimbine, respectively. Blood glucose levels were measured again 30 minutes later. Subsequently, 1.5 g / kg glucose was intraperitoneally injected, and blood glucose levels were continuously monitored.

[0057] (4) Insulin sensitivity test. Mice with a high-fat diet-induced type 2 diabetes model were tested after a 4-hour fast. After measuring fasting blood glucose levels, mice were gavaged with normal saline and 1.5 mg / kg yohimbine. Blood glucose levels were measured again 30 minutes later. Subsequently, 1.5 UI / kg of insulin was intraperitoneally injected, and blood glucose levels were continuously monitored.

[0058] The experimental results of Example 5 are shown in Figure 5. This experiment was conducted using mice with a high-fat diet-induced type 2 diabetes model. As shown in Figure A, oral administration of 1.5 mg / kg yohimbine significantly improved glucose tolerance compared to the saline group 1. As shown in Figure B, oral administration of 1.5 mg / kg yohimbine significantly improved insulin sensitivity compared to the saline group 1. The groups were compared using a two-way RM ANOVA, ****p<0.001. The horizontal axis represents time, and the vertical axis represents blood glucose levels.

[0059] Conclusion: The results showed that compared with the normal saline group, oral administration of yohimbine significantly reduced the fasting blood glucose level of type 2 diabetes model mice and significantly improved the blood glucose clearance ability after glucose injection.

[0060] The results showed that compared with the saline group, yohimbine injection significantly reduced the fasting blood glucose level of type 2 diabetes model mice and significantly improved insulin sensitivity.

[0061] 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.

[0062] (1) Experimental Animals. 8-10 week old C57BL / 6J mice were fed a 60% fat diet for 3 months, and their body weight and basal blood glucose levels increased significantly. Animal husbandry and experimental procedures adhered to the guidelines for animal care and protection of the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. These experimental animals were purchased from Jicui Yaokang.

[0063] (2) Experimental grouping and treatment. The experimental animals were divided into two groups, each with 8-9 animals. Each group was injected with normal saline or 1.5 mg / kg yohimbine. The injections were continued for 14 consecutive days, and blood glucose levels were measured daily before injection. The animals were administered by intraperitoneal injection with an injection volume of 10 ml / kg. A glucose tolerance test was performed on the 15th day.

[0064] (3) Free-diet blood glucose test: Mice were tail-clipped and blood was collected while on a normal diet. Blood glucose levels were measured using a Bayer blood glucose meter.

[0065] (4) Glucose tolerance test. Type 2 diabetes model mice were tested after a 16-hour fast. After measuring fasting blood glucose levels, 1.5 g / kg of glucose was intraperitoneally injected, and blood glucose levels were continuously monitored.

[0066] 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. As shown in Figure A, chronic 1.5 mg / kg yohimbine injection significantly increased the free diet blood glucose level of mice compared to the normal saline group 1. Figure B is the area under the curve data for Figure A. Figure C shows the glucose tolerance experiment. Figure D is the area under the curve data for 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. For 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. For Figures B and D, the comparison between groups was performed using T test.

[0067] Conclusion: The results showed that chronic yohimbine infusion significantly reduced free-feeding blood glucose levels compared with the saline group.

[0068] The results showed that the glucose clearance ability of mice in the chronic yohimbine administration group was significantly enhanced compared with the saline group.

Claims

1. The use of yohimbine in the treatment of type 2 diabetes.

2. The use of the Yohimbine drug according to claim 1 in treating type 2 diabetes, characterized in that: The yohimbine medicine includes yohimbine oral preparation and yohimbine injection.

3. The use of the Yohimbine drug as claimed in claim 2 in the treatment of type 2 diabetes, characterized in that: The yohimbine oral compound preparation includes yohimbine hydrochloride tablets, yohimbine sustained-release tablets, yohimbine sustained-release capsules, yohimbine enteric-coated tablets, yohimbine enteric-coated capsules, and yohimbine compound preparations.

4. The use of the Yohimbine drug according to claim 1 in treating type 2 diabetes, characterized in that: The yohimbine drug achieves the effect of treating type 2 diabetes by reducing fasting blood sugar, glucose tolerance and insulin tolerance of diabetic patients.

5. The use of the Yohimbine drug according to claim 1 in treating type 2 diabetes, characterized in that: Acute or chronic administration of yohimbine can significantly reduce fasting blood sugar, glucose tolerance, and insulin tolerance in diabetic patients, achieving the effect of treating type 2 diabetes.

6. The use of the Yohimbine drug according to claim 1 in treating type 2 diabetes, characterized in that: The dosage of the yohimbine drug for regulating blood sugar is 0.1 mg / kg to 10 mg / kg.

7. The use of the Yohimbine drug as claimed in claim 1 in treating type 2 diabetes, characterized in that: The dosage of the yohimbine drug for regulating insulin is 0.1 mg / kg to 10 mg / kg.

8. A method for treating type 2 diabetes, characterized in that: The subjects were given the drug Yobindin.

9. The method for treating type 2 diabetes according to claim 7, characterized in that: The yohimbine medicine includes yohimbine oral preparation and yohimbine injection.

10. The method for treating type 2 diabetes according to claim 8, characterized in that: The yohimbine oral compound preparation includes yohimbine hydrochloride tablets, yohimbine sustained-release tablets, yohimbine sustained-release capsules, yohimbine enteric-coated tablets, yohimbine enteric-coated capsules, and yohimbine compound preparations.

11. The method for treating type 2 diabetes according to claim 7, characterized in that: The dosage of the yohimbine drug for regulating blood sugar is 0.1 mg / kg to 10 mg / kg.

12. The method for treating type 2 diabetes according to claim 7, characterized in that: The dosage of the yohimbine drug for regulating insulin is 0.1 mg / kg to 10 mg / kg.

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