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Application of oral hypoglycemic peptide to preparation of medicine for treating or preventing diabetes complicated with cardiovascular diseases

A technology for diabetic cardiomyopathy and diabetes, applied in the field of biomedicine, can solve problems such as weight loss that is inferior to exenatide, no obvious cardiovascular benefits, and no treatment guidelines for diabetic cardiomyopathy.

Active Publication Date: 2020-11-10
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, there is no specific treatment guideline for diabetic cardiomyopathy. Drugs with both hypoglycemic and cardioprotective effects, represented by exenatide, have attracted widespread attention. However, some studies have found that some exenatide mutants have no obvious cardiac Vascular benefits, lixisenatide is one of the representative drugs
[0008] Lixisenatide removes the proline at the carboxyl end of exenatide and adds six lysines. In a head-to-head study with exenatide, it has the same effect as exenatide in lowering blood sugar and glycated hemoglobin. Quite, good hypoglycemic effect in clinical practice, but not as good as exenatide in weight loss
In clinical trials evaluating the cardiovascular effects of lixisenatide, lixisenatide failed to show favorable results, with no significant difference in cardiovascular events or hospitalization compared with placebo

Method used

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  • Application of oral hypoglycemic peptide to preparation of medicine for treating or preventing diabetes complicated with cardiovascular diseases
  • Application of oral hypoglycemic peptide to preparation of medicine for treating or preventing diabetes complicated with cardiovascular diseases
  • Application of oral hypoglycemic peptide to preparation of medicine for treating or preventing diabetes complicated with cardiovascular diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] This example is the establishment and grouping of rat models of diabetic cardiomyopathy.

[0032] The specific process is as follows:

[0033] Step 1: After 56 male Wistar rats were fed adaptively for one week, 8 were randomly selected as the control group and fed with normal feed throughout the whole process. STZ solution (made by dissolving streptozotocin STZ in pH 4.5, 0.1mol / L citrate buffer) was injected intraperitoneally for three consecutive weeks, while the control group was given corresponding volumes of pH 4.5, 0.1mol / L citrate buffer. One week later, the rats in the modeling group were cut off their tails to take blood and measure their fasting blood glucose with a blood glucose meter. The fasting blood glucose > 11.1mmol / L was used as the standard for successful modeling. fat diet for 4 weeks.

[0034] Step 2: Divide the rats in the model group into 6 groups: Semaglutide group (Semaglutide), Empagliflozin group (Empagliflozin), OHP2 high-dose group, OHP2 ...

Embodiment 2

[0039] This embodiment is the monitoring of blood sugar and body weight changes during the treatment of diabetic rats by OHP2.

[0040] Animal grouping and dosing regimen are as shown in Example 1. The fasting blood glucose was measured every week during the eight consecutive weeks of administration, and the body weight changes of the rats were recorded every day, and statistical analysis was performed.

[0041] The result is as figure 1 shown. Among them, changes in fasting blood glucose as figure 1 As shown in Figure A, the fasting blood glucose in the control group was lower than that of the other groups during the administration period; after eight weeks of administration, compared with the vehicle model group, the OHP2 high-dose group, the empagliflozin group and the semaglutide group The fasting blood glucose levels of the diabetic rats were significantly reduced, which indicated that OHP2 could effectively control the fasting blood glucose values ​​of diabetic rats. ...

Embodiment 3

[0044] This example is the effect of OHP2 on the heart function of diabetic rats.

[0045] Animal grouping and dosing regimen are as shown in Example 1. At the end of the eighth week of administration, echocardiography was used to detect rat heart function, and the specific process was as follows:

[0046] Step 1: Put the rats into a sealed anesthesia box, anesthetize with isoflurane inhalation, and fix in supine position.

[0047] Step 2: Dip an appropriate amount of depilatory cream with a cotton swab and apply it evenly on the chest of the rat, and use a scraper to remove the hair on the chest.

[0048] Step 3: Apply a small amount of conductive liquid to the limbs of the rat and fix it on the electrocardiographic sensor module, then apply an appropriate amount of ultrasonic coupling agent to the precordial area, adjust the position and find the heart image with the probe handle, collect the image and process the data.

[0049] The results of cardiac function tests such a...

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Abstract

The invention relates to application of an oral hypoglycemic peptide. The application is used for preparing a medicine or a medicine composition for treating or preventing diabetes complicated with cardiovascular diseases. The oral hypoglycemic peptide is polypeptide OHP2. The polypeptide can effectively improve myocardial hypertrophy and fibrosis damage caused by the diabetes, reduce the contentof related myocardial enzymes, adjust the lipid metabolism level and improve myocardial cell oxidative stress and mitochondrial damage, so that the effect of protecting the heart is achieved; and therefore, the polypeptide can be used as a candidate molecule for treating or preventing the diabetes complicated with the cardiovascular diseases (especially diabetic cardiomyopathy), and has a good application prospect.

Description

technical field [0001] The invention relates to the application of an oral hypoglycemic peptide in the preparation of medicines for treating or preventing diabetic cardiomyopathy, and belongs to the technical field of biomedicine. Background technique [0002] Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia and insulin resistance, which is caused by the relative insufficiency of insulin secretion to varying degrees caused by the interaction of various internal and external factors on the basis of genetic susceptibility. As of 2017, there were 425 million people with diabetes in the world. If no measures are taken, it is estimated that the number of people with diabetes may rise to 629 million by 2045, so diabetes has become a growing global health problem. Diabetic patients mostly die from complications of diabetes, and diabetic patients with cardiovascular disease have a high risk of death, which is 2-4 times higher than that of the general p...

Claims

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Application Information

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IPC IPC(8): A61K38/22A61P3/10A61P9/04
CPCA61K38/2278A61P3/10A61P9/04
Inventor 高向东田浤钱鹏姚文兵陆伟晟
Owner CHINA PHARM UNIV
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