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Method used for preparing compound or biodrug capable of enhancing CNPase activity and used for treating heart disease

A heart disease and compound technology, which is applied in the field of preparing compounds or biological drugs that enhance CNPase activity for the treatment of heart diseases, and can solve problems such as the decline of total ATP levels

Active Publication Date: 2021-03-12
ZHUHAI YUANZHI HEALTH TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the one hand, the change of energy metabolism substrate can reduce the oxygen consumption required to generate each mole of ATP, that is, it can reduce the generation of reactive oxygen species (Reactive Oxygen Species, ROS) in cells; but on the other hand, this change is inevitable There are a large number of unfavorable factors, such as chronic fatty acid aerobic oxidation disorders leading to lipid accumulation in cardiomyocytes, lactic acid accumulation, and a decrease in total ATP levels caused by increased glycolysis.

Method used

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  • Method used for preparing compound or biodrug capable of enhancing CNPase activity and used for treating heart disease
  • Method used for preparing compound or biodrug capable of enhancing CNPase activity and used for treating heart disease
  • Method used for preparing compound or biodrug capable of enhancing CNPase activity and used for treating heart disease

Examples

Experimental program
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Effect test

Embodiment 1

[0029] This case mainly illustrates that isosteviol sodium enhances CNPase activity in angiotensin II-induced cardiac hypertrophic cells. The calf intestinal alkaline phosphatase activity detection method was used to detect the enzyme activity of CNPase in hypertrophic myocardial samples after administration of isosteviol.

[0030] Table 1. Isosteviol Sodium Can Enhance CNPase Activity in Cardiac Hypertrophy Induced by Angiotensin II (n=3)

[0031]

Embodiment 2

[0033] This case mainly illustrates the role of overexpression of CNPase in improving TAAC-induced cardiac hypertrophy.

[0034] Adult SD rats were treated with AAV-CNPase after TAAC induction for 2 weeks. Heart to body weight ratio (HW / BW) is an index reflecting cardiac hypertrophy. In the 8-week TAAC model group, we found that the heart weight ratio (HW / BW) of rats in the TAAC group was significantly increased; and overexpression of CNPase could effectively reduce the heart weight ratio.

[0035] Table 2. Effect of overexpression of CNPase on heart weight and body weight of TAAC model rats (n=8-14)

[0036]

Embodiment 3

[0038] This case mainly illustrates the role of AAV-CNPase in inhibiting the formation of myocardial fibrosis.

[0039] To determine whether overexpression of CNPase could attenuate TAAC-induced myocardial fibrosis, we detected changes in left ventricular myocardium interstitial collagen using Masson staining. We found that myocardial fibrosis and collagen deposition increased in rats in TAAC group; overexpression of CNPase could effectively reduce myocardial fibrosis and collagen deposition.

[0040] Table 3. Overexpression of CNPase inhibits the formation of myocardial fibrosis in TAAC model rats (n=8-14)

[0041]

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PUM

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Abstract

The invention relates to a method used for preparing a compound or a biodrug capable of enhancing CNPase activity and used for treating heart disease. According to the invention, chemical methods involve up-regulating the expression and activity of CNPase by using kaurane compounds; Biological therapeutic agents relate to the preparation of CNPase enzymes expressed by using recombinant adeno-associated viruses and therapies of local intervention; and in a rat myocardial hypertrophy and heart failure model, the method can effectively improve myocardial hypertrophy and myocardial remodeling, inhibit myocardial hypertrophy and fibrosis increase and increase cardiac functions.

Description

Background technique [0001] 2',3'-cyclic nucleotide-3'-phosphodiesterase (2',3'-cyclic nucleotide3'-phosphodiesterase, CNPase) was discovered in the early 1960s, with the ability to catalyze 2', 3'-cAMP and The function of 2', 3'-cGMP degradation is highly expressed in the central nervous system. The release of extracellular 2', 3'-cAMP is associated with injury, and 2', 3'-cAMP can activate mitochondrial permeability transition pores (mPTPs) leading to apoptosis. It is currently found that 2', 3'-cAMP and CNPase are related to mitochondrial membrane permeability. Jackson EK et al. reported that CNPase knockout can protect renal function in ischemia / reperfusion (J Am Soc Nephrol.2016). So far, no one has reported the target and function of CNPase in cardiomyopathy. [0002] Heart failure is a severe manifestation or advanced stage of various heart diseases, with high mortality and rehospitalization rates. Heart failure is a group of complex clinical syndromes caused by abno...

Claims

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Application Information

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IPC IPC(8): A61K31/19A61P9/00A61P9/10A61P9/04C12N15/864A01K67/027
CPCA61K31/19A61P9/00C12N15/1137A61P9/04A61K48/0041C12N2310/141
Inventor 王东方陈凯欣卢志强谭文
Owner ZHUHAI YUANZHI HEALTH TECH CO LTD
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