Application of an oral hypoglycemic peptide in the preparation of drugs for treating or preventing diabetes complicated with cardiovascular disease

A diabetes and drug technology, applied in the field of biomedicine, can solve problems such as exenatide in weight loss, no obvious cardiovascular benefits, and no treatment guideline for diabetic cardiomyopathy

Active Publication Date: 2022-06-28
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 an oral hypoglycemic peptide in the preparation of drugs for treating or preventing diabetes complicated with cardiovascular disease
  • Application of an oral hypoglycemic peptide in the preparation of drugs for treating or preventing diabetes complicated with cardiovascular disease
  • Application of an oral hypoglycemic peptide in the preparation of drugs for treating or preventing diabetes complicated with cardiovascular disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0032] The specific process is as follows:

[0033] Step 1: After 56 male Wistar rats were adaptively fed for one week, 8 rats were randomly selected as the control group and fed with normal chow throughout the whole process. The dose of STZ solution (prepared by dissolving streptozotocin STZ in pH4.5, 0.1mol / L citrate buffer) for three consecutive weeks, while the control group was given the corresponding volume of pH4.5, 0.1mol / L citrate buffer. One week later, the rats in the model group were subjected to tail-dock blood collection to measure fasting blood glucose with a blood glucose meter. Fasting blood glucose > 11.1 mmol / L was used as the criterion for successful modeling, and the unqualified rats were eliminated, and the qualified rats continued to receive high blood glucose. Fat diet for 4 weeks.

[0034] Step 2: The rats in the modeling group were divided into 6 group...

Embodiment 2

[0039] This example is the monitoring of blood glucose and body weight changes during the treatment of OHP2 in diabetic rats.

[0040] Animal grouping and dosing schedule are shown in Example 1. Fasting blood glucose was measured weekly during the eight-week dosing period, and changes in body weight of rats were recorded every day, and statistical analysis was performed.

[0041] The result is as figure 1 shown. Among them, fasting blood glucose changes such as figure 1 As shown in Figure A, the fasting blood glucose of 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 of the rats was significantly reduced, which indicated that OHP2 could effectively control the fasting blood glucose of diabetic rats.

[0042] Changes in rat body weight as figure 1 As show...

Embodiment 3

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

[0045] Animal grouping and dosing schedule are shown in Example 1. At the eighth weekend of administration, the cardiac function of the rats was detected by echocardiography. The specific process is as follows:

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

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

[0048] Step 3: Apply a small amount of conductive fluid to the limbs of the rat and fix it on the ECG induction module, then apply an appropriate amount of ultrasonic couplant to the precordial area, adjust the position and use the probe handle to find the heart image, collect the image and process the data.

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

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Abstract

The invention relates to the application of an oral hypoglycemic peptide, which is used for preparing medicine or pharmaceutical composition for treating or preventing diabetes complicated with cardiovascular disease. The oral hypoglycemic peptide is polypeptide OHP2. The polypeptide can effectively improve the myocardial hypertrophy and fibrosis damage caused by diabetes, reduce the content of related myocardial enzymes, regulate the level of lipid metabolism, improve myocardial cell oxidative stress and mitochondrial damage, and thus play a role in protecting the heart. Therefore, the polypeptide can As a candidate molecule for treating or preventing diabetes complicated with cardiovascular disease (especially diabetic cardiomyopathy), it has a good application prospect.

Description

technical field [0001] The invention relates to the application of an oral hypoglycemic peptide in the preparation of a drug 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 in different degrees due to the interaction of multiple internal and external factors on the basis of genetic susceptibility. As of 2017, there were 425 million people with diabetes worldwide, and if nothing is done, the number of people with diabetes is expected to rise to 629 million by 2045, so diabetes has become a growing global health problem. Diabetic patients mostly die from diabetic complications, among which diabetic patients complicated with cardiovascular disease have a high risk of death, 2-4 times higher than the general population, account...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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