A novel natriuretic peptide chimera c with anti-heart failure activity n aa c

A technology for heart failure and natriuretic peptides, applied in the fields of peptide/protein components, medical preparations containing active ingredients, peptides, etc., can solve problems such as high cost, limited application, and easy degradation by the body

Inactive Publication Date: 2017-09-29
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Abstract
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AI Technical Summary

Problems solved by technology

Artificially synthesized ANP and BNP analogues have been widely used in HF treatment, but their application has been limited due to problems such as low chemical synthesis efficiency, high cost, and easy degradation by the body.

Method used

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  • A novel natriuretic peptide chimera c with anti-heart failure activity <sub>n</sub> aa <sub>c</sub>
  • A novel natriuretic peptide chimera c with anti-heart failure activity <sub>n</sub> aa <sub>c</sub>
  • A novel natriuretic peptide chimera c with anti-heart failure activity <sub>n</sub> aa <sub>c</sub>

Examples

Experimental program
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Embodiment Construction

[0059] 1. C N AAA C design philosophy ( Figure 9 )

[0060] 2. Rat isolated blood vessel ring perfusion experiment

[0061] (1) C N AAA c Study on Vascular Relaxation Effect and Effect of Vascular Endothelium on Relaxation

[0062] Adult healthy male SD rats were anesthetized by intraperitoneal injection of pentobarbital sodium (40mg / kg), and the abdominal aorta was quickly separated and cut, placed in pre-cooled oxygen-saturated K-H solution, and the perivascular area was carefully removed with microscopic tweezers. The connective tissue, prepare a ring specimen with a growth of about 3mm. Suspend the vascular loop at 37°C with continuous perfusion of 95% O 2 and 5% CO 2 Kreb’s liquid bath of mixed gas. A tension transducer was connected to record changes in the tension of the vascular ring, and the preload (base tension) of the abdominal aortic ring was set at 1 g. After equilibrating for 1h, add NE (10 -6 M) Cause vasoconstriction as a pre-stimulation (those who...

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Abstract

The invention discloses a novel natriuretic peptide chimera CNAAc which has the functions of vasodilation, diuresis and myocardial protection. The CNAAc is a novel natriuretic peptide molecule formed by adding an annular structure of ANP (Atriopeptin) and c-terminus on an amino terminal of CNP (C-type Natriuretic Peptide) (as shown in the drawing). The natriuretic peptide chimera has the functions of endothelium-independent vasodilation and strong diuresis. The vasodilation function of the natriuretic peptide chimera CNAAc is greatly superior to that of the natural natriuretic peptide ANP or CNP, and the natriuretic peptide chimera CNAAc possibly exerts the effec through an NPR / cGMP / PKG signal channel. The CNAAc can be used for obviously inhibiting the cardiac hypertrophy of a rat during the generation of the cardiac failure and improving the myocardial enzymology indexes and the cardiac functions of the rat so as to obviously relieve the myocardial infarction degree and the myocardial fibrosis degree of the rat with the cardiac failure. The novel natriuretic peptide chimera with the functions of the myocardial protection and the cardiac failure resistance can be applied to academic research and can be possibly prepared into novel medicines for preventing and treating cardiac failure in clinical application. Thus, the novel natriuretic peptide chimera has good scientific research values and clinical application prospects.

Description

technical field [0001] The invention relates to the fields of basic research and clinical research of using novel natriuretic peptide drugs to prevent and treat heart failure. Background technique [0002] Cardiovascular and cerebrovascular diseases are recognized as the "No. 1 killer" of human health in the world, and heart failure is the almost inevitable outcome of many organic heart diseases such as myocardial infarction, cor pulmonale, hypertrophic cardiomyopathy, etc., a serious threat human health. The natriuretic peptide family has been widely used in basic and clinical research on heart failure because of its diverse effects such as significant natriuresis, diuresis, vasodilator and anti-proliferation. [0003] The natriuretic peptide family is a family of endogenous peptides with similar structures, and its members include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide ( C-type natriuretic peptide (CNP) and D-type na...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K38/22A61P9/04
Inventor 裴建明张淑苗王跃民朱妙章李娟冯娜顾晓明樊荣郭海涛贾敏
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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