Application of Miconazole in Prevention of Vascular Rupture

A technology of miconazole and blood vessels, which is applied in the application field of miconazole in the prevention of vascular rupture, and can solve the problems of poor prevention effect

Active Publication Date: 2019-07-23
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In order to solve the current situation of poor prevention of various diseases caused by abnormal blood ve

Method used

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  • Application of Miconazole in Prevention of Vascular Rupture
  • Application of Miconazole in Prevention of Vascular Rupture
  • Application of Miconazole in Prevention of Vascular Rupture

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] O-dianisidine staining can mark the number and location of red blood cells in living embryos, so the difference in red blood cell level between zebrafish cerebral hemorrhage mutants and non-hemorrhagic embryos can be compared. In embryos 2 days after fertilization, the red blood cells of non-hemorrhagic embryos were distributed in the heart, common main vein, dorsal aorta, and other major blood vessels; Red blood cells were significantly reduced, while the accumulation of red blood cells in the brain of embryos treated with miconazole was significantly improved, and the number of total main vein red blood cells increased. This shows that miconazole has a significant inhibitory effect on the hemorrhagic phenotype of the zebrafish cerebral hemorrhage mutant, but does not affect the number of red blood cells.

[0030] The hemorrhage inhibitory effect of miconazole on zebrafish intracerebral hemorrhage mutants was enhanced with the increase of drug concentration, and micona...

Embodiment 2

[0055] Metal matrix proteases (MMPs) in extracellular matrix proteins are one of the important components to maintain vascular stability (Xing et al., 2012). Increased expression of extracellular MMPs enhances the proteolysis process in the extracellular matrix (ECM), which is beneficial to cell division and migration during development. MMPs are also crucial regulators of inflammation during brain injury (del Zoppo, 2010).

[0056] There are many members of the MMP family in the zebrafish genome, of which only six are well annotated: mmp2, mmp9, mmp13b, mmp14a, mmp14b and mmp23aa. Therefore, first of all, we used quantitative PCR to detect the transcription of these six genes. The embryos of wild-type, cerebral hemorrhage mutants and miconazole-treated mutants were taken 2 days after fertilization. Quantitative PCR found that only the expression of mmp9 was significantly increased in the mutants, while in the miconazole-treated mutants The expression level in the middle gro...

Embodiment 3

[0082]Previous studies have shown that there is a rather tight link between MMP9 and extracellular signal-regulated kinases 1 and 2 (ERK1 / 2) in the regulation of transcriptional and post-transcriptional levels (Garavello et al., 2010). MMP9 can be induced to express, and its expression is regulated by many transcription factors, including activator proteins 1 and 2 (AP1 / 2), specialized protein 1 (SP1), NF-B, and polyoma enhancer A-binding protein 3 / Ets ( PEA3 / Ets) (St-Pierre et al., 2004). Through the Ras / Raf / MEK / ERK pathway, these transcription factors are activated and translocated into the nucleus to regulate the expression of MMP9 (Chang et al., 2011; Garavello et al., 2010; Wu et al., 2013). The regulation of ERK1 / 2 on MMP9 is very complex, even showing completely opposite trends in different types of cells. However, it is more certain that MEK / ERK activates the overexpression of MMP9 in many neurological diseases such as ischemic stroke (Maddahi et al., 2009). Therefor...

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Abstract

The invention relates to application of miconazole to preparation of drugs used for preventing vascular rupture. The invention also relates to application of miconazole as a MMP9 inhibitor in vascular peripheral cells. The invention also relates to application of miconazole as an ERK inhibitor in vascular peripheral cells. The invention further relates to a pharmaceutical composition for preventing vascular hemorrhage, wherein the main drug effect component of the pharmaceutical composition is miconazole. The invention also relates to a pharmaceutical composition for inhibiting MMP9 expression in vascular peripheral cells, wherein the main drug effect component of the pharmaceutical composition is miconazole. The invention also relates to a pharmaceutical composition for inhibiting phosphorylation of ERK in vascular peripheral cells, wherein the main drug effect component of the pharmaceutical composition is miconazole. The invention also relates to a pharmaceutical composition which contains U0126 and miconazole. The invention further relates to application of miconazole to prevention of abnormal vascular rupture. The invention also provides novel application of miconazole to prevention of abnormal vascular hemorrhage. Miconazole can effectively prevent a plurality of diseases caused by vascular hemorrhage.

Description

technical field [0001] The invention relates to the application of miconazole in preventing blood vessel rupture. Background technique [0002] Abnormal rupture of blood vessels can lead to the occurrence of various diseases. Cardiovascular disease has long been the leading cause of death worldwide, with stroke ranking the top three. In 2012, more than 6.7 million people died of stroke worldwide, accounting for about 17% of the total mortality from non-communicable diseases (WHO, 2015). Hemorrhagic stroke accounts for only 10-15% of all strokes, but its incidence and mortality are much higher. [0003] Despite the considerable morbidity and mortality of hemorrhagic stroke, the molecular pathology of ischemic stroke is poorly understood. Recent studies have pointed out that the inflammatory response is the main cellular event after hemorrhagic stroke, accompanied by neuronal death, leukocyte infiltration, and activation of microglia / macrophages and astrocytes, the main inf...

Claims

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Application Information

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IPC IPC(8): A61K31/4174A61K31/277A61P9/10A61P9/00
CPCA61K31/277A61K31/4174A61K2300/00
Inventor 熊敬维刘振明韩晶岩杨冉朱小君
Owner PEKING UNIV
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