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Application of FG4592 in preparation of medicine for preventing and treating chronic kidney disease caused by ischemia-reperfusion injury

A technology for chronic kidney disease and ischemia-reperfusion, applied in drug combinations, cardiovascular system diseases, pharmaceutical formulations, etc.

Inactive Publication Date: 2021-09-10
NANJING CHILDRENS HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no evidence that FG4592 has the effect of preventing and treating chronic kidney disease caused by ischemia-reperfusion injury

Method used

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  • Application of FG4592 in preparation of medicine for preventing and treating chronic kidney disease caused by ischemia-reperfusion injury
  • Application of FG4592 in preparation of medicine for preventing and treating chronic kidney disease caused by ischemia-reperfusion injury
  • Application of FG4592 in preparation of medicine for preventing and treating chronic kidney disease caused by ischemia-reperfusion injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] 10mg / kg therapeutic dose of FG4592 treated for 18 days had no toxic side effects on mice.

[0039] 1) Experimental materials

[0040] The C57BL / 6 mice used in the present invention were purchased from the Institute of Model Animals of Nanjing University; FG4592 was purchased from Selleck Company, and the 50 mg / mL mother liquid was prepared in DMSO and stored in a refrigerator at -80 degrees.

[0041] 2) Experimental method

[0042]Twelve male C57BL / 6 mice (7 weeks old, weighing 20-24g) were raised in an SPF-grade barrier environment in the Experimental Animal Center of Nanjing Medical University. The animals ate freely and maintained a circadian rhythm of 12 hours of light and 12 hours of darkness. After one week of adaptive feeding, they were randomly divided into control group (n=6) and FG4592 (FG) group (n=6). The mice in the FG group were treated with FG4592 (10 mg / kg) by intraperitoneal injection for 18 consecutive days; the mice in the control group were given t...

Embodiment 2

[0046] FG4592 promotes angiogenesis in renal tissue of ischemia-reperfusion mice.

[0047] 1) Experimental materials

[0048] The HIF1α antibody used in the present invention was purchased from Abcam; the VEGFA, VEGFR1, and GAPDH antibodies were purchased from ProteinTech; the CD31 antibody was purchased from CST; the HRP-labeled GoatAnti-Rabbit secondary antibody was purchased from Beyond Biotechnology Co., Ltd.; immunohistochemical reagents The box was purchased from Beijing Zhongshan Jinqiao Company; other biological materials and chemical materials were the same as in Example 1.

[0049] 2) Experimental method

[0050] Establishment of animal model and administration method

[0051] Thirty-six male C57BL / 6 mice (7 weeks old, weighing 20-24g) were raised in an SPF-grade barrier environment in the Experimental Animal Center of Nanjing Medical University. The animals ate freely and maintained a circadian rhythm of 12 hours of light and 12 hours of darkness. After one week ...

Embodiment 3

[0061] FG4592 promotes MAEC angiogenesis in mouse vascular endothelial cells.

[0062] 1) Experimental materials

[0063] Mouse vascular endothelial cells MAEC were purchased from ATCC; β-Actin antibody was purchased from CST; dual luciferase reporter gene detection kit was purchased from Promega; Lipofectamine 2000 was purchased from Invitrogen; Matrigel was purchased from Corning.

[0064] 2) Experimental method

[0065] Cell culture and drug treatment

[0066] Mouse vascular endothelial cells MAEC were cultured in DMEM medium containing 10% fetal bovine serum, containing 100 U / mL penicillin and 0.1 mg / mL streptomycin, and the culture conditions were 37°C, 5% carbon dioxide and 95% air. When the cell density was 90%, trypsinized and subcultured, and seeded in 6-well plates. On the next day, the FG4592 stock solution was diluted into serum-free medium to the final concentration (5 and 10 μg / mL, 0.1% DMSO), and the control cells were treated with serum-free medium containin...

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Abstract

The invention provides application of FG4592 in preparation of a medicine for preventing and treating chronic kidney diseases caused by ischemia-reperfusion injury. The application is characterized in that a new candidate compound is provided for the chronic kidney diseases caused by the ischemia-reperfusion injury; the FG4592 is an HIF prolyl hydroxylase activity inhibitor. In addition, the FG4592 can be prepared into a composition of the medicine for the chronic kidney diseases. Specifically, the FG4592 can promote neogenesis of kidney blood vessels, relieve the kidney oxidative stress caused by the ischemia-reperfusion injury and reduce the kidney fibrosis level. The application range of the FG4592 is expanded; the FG4592 is used as the candidate compound for preventing and treating the chronic kidney diseases caused by the ischemia-reperfusion injury to be developed and applied.

Description

technical field [0001] The present invention relates to the application of FG4592 (Roxadustat) in the preparation of drugs, in particular to a new application of FG4592 in the preparation of drugs for chronic kidney disease caused by ischemia-reperfusion. Background technique [0002] Renal ischemia-reperfusion injury (IRI) is a pathological phenomenon in which renal function cannot return to normal due to insufficient blood supply to the kidney followed by restoration of blood perfusion, and even aggravates its dysfunction and structural damage. Due to its tissue function and structural characteristics, the kidney has a high demand for oxygen and is one of the organs sensitive to IRI. Clinically, renal IRI often occurs after renal transplantation, microcirculation recanalization after shock, and cardiac surgery. It is one of the main causes of acute kidney injury, and the fatality rate accounts for 20% of hospitalized patients. 19%-31% eventually develop into chronic kidne...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/472A61P9/10A61P13/12
CPCA61K31/472A61P9/10A61P13/12
Inventor 吴梦秋张爱华贾占军李树珍公伟于婧于晓文杨运文游然陈维宜
Owner NANJING CHILDRENS HOSPITAL
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