Application of PEDF (pigment epithelium derived factor) and derivatives thereof in preparing drug for reconstructing coronary artery reserved collateral microcirculation and drug screening method

A technology of coronary artery and screening method, applied in the field of biomedicine, can solve problems such as myocardial infarction that cannot be repaired well, achieve high functional selectivity and improve curative effect.

Active Publication Date: 2018-08-14
华融(徐州)生物医药科技发展研究院有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are many treatment options, the conventional treatment used has outstanding problems such as not being able to repair the infarcted myocardium well.

Method used

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  • Application of PEDF (pigment epithelium derived factor) and derivatives thereof in preparing drug for reconstructing coronary artery reserved collateral microcirculation and drug screening method
  • Application of PEDF (pigment epithelium derived factor) and derivatives thereof in preparing drug for reconstructing coronary artery reserved collateral microcirculation and drug screening method
  • Application of PEDF (pigment epithelium derived factor) and derivatives thereof in preparing drug for reconstructing coronary artery reserved collateral microcirculation and drug screening method

Examples

Experimental program
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Effect test

Embodiment 1

[0069] see figure 1 , to establish an acute myocardial infarction model, inject lectin-FITC into the systemic circulation of rats through the femoral vein, and the lectin-FITC will reach blood vessels at all levels along with the discharge of the heart, and bind to glycoproteins on the surface of vascular endothelial cells. We use this method to label blood flow in real time. Samples were taken immediately, 5 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 6 hours after coronary artery ligation. result( figure 1 C and 1D) showed that in the 0min ligation group, there were almost no perfused vessels in the downstream area of ​​the occlusion, while in the 5min ligation group, the density of lectin-labeled blood vessels in the same area was more than that of the sham operation group, indicating that there were more blood vessels than the original The blood vessels with a large number of vessels have blood flow through them at this time, and we named this phenomenon coronary c...

Embodiment 2

[0071] Male adult SD rats were used to establish an animal model of acute myocardial infarction pre-transfected with lentivirus and a ligature was reserved (see Materials and Methods). Using methods such as direct myocardial injection, systemic intravenous injection, local coronary artery injection, sublingual administration or injection, intraperitoneal injection, nasal mucosal spray or injection, pulmonary aerosolization, rectal administration, intramuscular injection or oral administration, etc., give different drugs respectively. Chemical molecular drugs loaded in liposomes, polycationic carriers, polyanion carriers, targeting peptides, plasmid vectors, adenoviral vectors, adenovirus-associated vectors or lentiviral vectors, or biomolecular drugs. Two weeks later, the ligature was tightened and the lectin-FITC was injected into the systemic circulation of the rats through the femoral vein, and samples were collected immediately, 5 minutes, 30 minutes, 1 hour, 2 hours, 4 ho...

Embodiment 3

[0073] Male adult SD rats were used to establish an acute myocardial infarction model. After thoracotomy, a ligation line was reserved under the left anterior descending coronary artery, and PEDF carrier lentivirus was injected directly into the perfusion area of ​​the left anterior descending coronary artery (for surgical methods, see Materials Methods Establishment of animal model of acute myocardial infarction in rats pre-transfected with lentivirus). In addition, a pre-transfected empty vector virus group was established as a negative control group. The ligature was tightened two weeks later, and samples were taken immediately, 5 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours later. Subsequent observations and photographs were taken under a fluorescence microscope. The results showed that the number of open CCMR blood vessels in the infarct area of ​​the rat hearts pre-transfected with PEDF for two weeks decreased, but the diameter of the blood vessels was sig...

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Abstract

The invention discloses application of PEDF (pigment epithelium derived factor) and derivatives thereof in preparing a drug for reconstructing coronary artery reserved collateral microcirculation anda drug screening method. The application comprises application of the PEDF in preparing the drug for reconstructing the coronary artery reserved collateral microcirculation, and application of PEDF derivative polypeptide in preparing the drug for reconstructing the coronary artery reserved collateral microcirculation, wherein the PEDF derivative polypeptide comprises 44 to 77aa polypeptide segments of the PEDF. The invention further comprises the screening method of the drug for reconstructing the coronary artery reserved collateral microcirculation. The drug for reconstructing the coronary artery reserved collateral microcirculation, disclosed by the invention, has the advantages that perfusion function can be improved, effective perfusion time is prolonged, stable connection of coronaryartery reserved collateral microcirculation vascular endothelial cells is promoted, leakage of coronary artery reserved collateral microcirculation blood vessels is stopped, side interstitial edema ofthe coronary artery reserved collateral microcirculation blood vessels is relieved and heart functions are improved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of PEDF and its derivatives in the preparation of drugs for reconstructing coronary reserve collateral microcirculation and a drug screening method. Background technique [0002] Currently, acute myocardial infarction (AMI) is still one of the leading causes of death and disability worldwide. The main treatment methods for AMI include drugs, intervention, surgery, symptomatic treatment and mesenchymal stem cell inhibitory treatment, etc. The purpose is to improve myocardial ischemia and hypoxia, prevent arrhythmia, and maintain better cardiac perfusion. Although there are many treatment options, the conventional treatments used all have outstanding problems such as not being able to repair the infarcted myocardium well. Therapeutic angiogenesis can promote the growth of capillaries and the establishment of collateral circulation, and the treatment ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/57A61K38/18A61P9/10A61K49/00
CPCA61K38/18A61K38/57A61K49/0008A61P9/10
Inventor 董红燕张中明苗浩然刘修成黄兵袁延亮刘志伟
Owner 华融(徐州)生物医药科技发展研究院有限公司
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