Pharmaceutical application of Sonidegib in treatment of aortic dissection

A technology for aortic dissection and drugs, applied to medical preparations containing active ingredients, pharmaceutical formulas, drug combinations, etc.

Inactive Publication Date: 2021-07-06
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether Sonideji can inhibit the occurrence of aortic dissection and its mechanism have not yet had any relevant research and reports.

Method used

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  • Pharmaceutical application of Sonidegib in treatment of aortic dissection
  • Pharmaceutical application of Sonidegib in treatment of aortic dissection
  • Pharmaceutical application of Sonidegib in treatment of aortic dissection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] At the animal level, Sonideji reduces the incidence of aortic dissection and improves aortic elastic fiber integrity in mice with aortic dissection. In order to explore the regulatory effect of Sonideji on aortic dissection, we selected SPF grade 3-week-old male C57BL / 6J mice (purchased from the Medical Experimental Animal Center of Nanjing Medical University) and randomly divided them into 3 groups: control group, aortic dissection model group (0.25% BAPN drinking water, 28 days) and the group of mice with aortic dissection given Sonideji (30 mg / kg / day, 28 days) by intragastric administration, the survival of the mice was observed every day, and after 4 weeks, the small Mouse aorta. Gross pictures and H&E tissue staining of aortic dissection model mice drinking water alone showed obvious pathological dilatation of the aorta (Figure 1: A, D), and ultrasound examination showed ascending aorta / descending aorta / thoracic aorta The diameter was about 1.5 times that of the c...

Embodiment 2

[0020] At the cellular level, administration of sonideji inhibited the angiotensin-2-induced increase in the migration of human umbilical vein endothelial cells (Figure 3). Immunofluorescence detection showed that the expression of VE-cadherin decreased after treatment with angiotensin 2 in human umbilical vein endothelial cells; on this basis, the expression of VE-cadherin increased after administration of sonideji. The above results suggest that Sonideji can delay the progression of aortic dissection by inhibiting the damage of intercellular junctions of endothelial cells (Figure 4).

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Abstract

The invention discloses pharmaceutical application of Sonidegib in treatment of aortic dissection, and relates to the field of cardiovascular systems. After Sonidegib is administered to aortic dissection model mice through intragastric administration, aortic pathological expansion can be effectively inhibited, the death rate and the occurrence rate of aortic dissection can be reduced, and meanwhile, aortic vascular endothelial cell connection injury of the aortic dissection mice can be relieved; and human umbilical vein endothelial cells (HUVECs) are stimulated by angiotensin 2, and after Sonidegib is given to the HUVECs, the connection injury of the HUVECs can be inhibited.

Description

technical field [0001] The invention belongs to the technical field of aortic dissection treatment, and in particular relates to the pharmaceutical use of smoothened (SMO) protein inhibitor sonideji in preventing and treating aortic dissection. Background technique [0002] Aortic dissection (AD) is a life-threatening disease caused by a tear in the aortic intima or bleeding in the aortic wall. AD has acute onset, rapid progression, complex clinical manifestations, high fatality rate, and poor prognosis. It is a very dangerous cardiovascular disease that seriously threatens human health. Therefore, early prevention and treatment are particularly important. The current clinical use of drugs mainly slows down the disease process by controlling blood pressure, heart rate, blood lipids and other indicators, and there are many adverse reactions and side effects, and no specific drugs for prevention and treatment have been found. Therefore, there is a need for safer and more ef...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5377A61P9/14
CPCA61K31/5377A61P9/14
Inventor 季勇陈钰榕张佳苗子安谢利平林喆
Owner NANJING MEDICAL UNIV
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