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Application of DLL4 cytokine in preparation of medicine for treating fulminant hepatic failure

A technology of liver failure and cytokines, applied in the fields of clinical medicine, molecular medicine and regenerative medicine, can solve the problems of donor liver shortage and patient death, reduce bilirubin level, promote new angiogenesis, and reduce degeneration and necrosis Effect

Active Publication Date: 2016-01-27
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But due to a severe shortage of donor livers, a large number of patients died while waiting for a liver transplant

Method used

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  • Application of DLL4 cytokine in preparation of medicine for treating fulminant hepatic failure
  • Application of DLL4 cytokine in preparation of medicine for treating fulminant hepatic failure
  • Application of DLL4 cytokine in preparation of medicine for treating fulminant hepatic failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1: Injection containing DLL4 cytokines treats a large animal (young pig) model of fulminant hepatic failure

[0044] Animal model: 30 male Chinese young pigs (8-10 kg) were randomly divided into two groups, 15 in each group. Each young pig was injected with 1.5g / kg D-gal via the jugular vein to create a model of fulminant hepatic failure.

[0045] Test group: multiple intravenous injections of DLL4 injection at fixed time points after D-gal injection, dose: 10ml / kg, twice a day.

[0046] Control group: inject the same amount of normal saline without DLL4.

[0047] Neither the control group nor the experimental group received other drug treatment.

[0048] figure 1 It is a schematic diagram of the survival time curves of the young pigs of the experimental group and the control group, showing the survival rate of the young pigs of the experimental group and the control group. The results showed that the 3-day survival rate of young pigs in the treatment gro...

Embodiment 2

[0049] Example 2: The small animal (rat) model of fulminant hepatic failure treated by lyophilized powder injection containing DLL4 cytokine

[0050] Animal model: 100 male rats (200-250 g) were randomly divided into two groups, 50 in each group. Each rat was intraperitoneally injected with D-gal 1.5g / kg to make a model of fulminant hepatic failure. DLL4 lyophilized powder and water for injection are prepared into a suspension.

[0051] Experimental group: 4 ml of DLL4 lyophilized powder suspension was injected intraperitoneally at a fixed time point after D-gal injection, twice a day.

[0052] Control group: inject the same amount of normal saline without DLL4.

[0053] Both the control group and the experimental group received no other drug treatment.

[0054] figure 2 Schematic diagram of the survival time curves of rats in the experimental group and the control group, figure 2The survival rates of the rats in the experimental group and the control group were shown: ...

Embodiment 3

[0055] Example 3: The suspension containing DLL4 cytokines treats a rabbit model of fulminant hepatic failure

[0056] Animal model: 40 adult male rabbits (2000-2500 g) were randomly divided into two groups, 20 in each group. Each rabbit was intramuscularly injected D-gal 1.5g / kg to make a model of fulminant hepatic failure.

[0057] Test group: Intramuscular injection of DLL4 suspension 20ml at a fixed time point after D-gal injection, twice a day.

[0058] Control group: inject the same amount of normal saline without DLL4.

[0059] Both the control group and the experimental group received no other drug treatment.

[0060] image 3 It is a schematic diagram of the survival time curves of rabbits in the experimental group and the control group, image 3 The survival rate of the rabbits in the experimental group and the control group is expressed: the results show that the survival rate of the rabbits in the DLL4 treatment group is 95% at 3 days, 90% at 7 days, and 90% at...

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Abstract

The present invention discloses application of DLL4 cytokine in preparation of a medicine for treating fulminant hepatic failure, the medicine includes a DLL4 cytokine pharmaceutically acceptable excipient, an antioxidant and a carrier, the form of medicine can be an injection liquid or frozen dry powder or a suspension, the application temperature of the medicine including the DLL4 cytokine is 15 DEG C-30 DEG C, and the humidity is 45%-75%. Studies on the aspects of biochemical indexes, immunohistochemistry, gene expression level, proteomics and the like show that the DLL4 cytokine can be used in preparation of the medicine for effectively treating fulminant hepatic failure, and different dosages and forms of medicines can be produced by compounding the DLL4 cytokine with different solvents and stabilizers.

Description

technical field [0001] The invention belongs to the fields of clinical medicine, molecular medicine and regenerative medicine, and specifically relates to a new technology for treating fulminant hepatic failure with DLL4 cytokine series drugs. Background technique [0002] Fulminant hepatic failure is a kind of disease caused by extensive necrosis of the liver caused by various reasons. Except for orthotopic liver transplantation, there is currently no specific treatment. However, due to the severe shortage of donor livers, a large number of patients died while waiting for liver transplantation. If we can find one or more cytokines that can not only inhibit liver necrosis, but also quickly induce host liver tissue regeneration and long-term function, and avoid potential side effects, it will be of great significance for the treatment of fulminant liver failure caused by various reasons. extremely important. DLL4 cytokine is a type I transmembrane protein located on the ce...

Claims

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Application Information

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IPC IPC(8): A61K38/19A61P1/16
CPCA61K38/19
Inventor 李君李兰娟陈新李江
Owner ZHEJIANG UNIV
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