Use of ligustrazine phosphate in preparing medicine for treating dilated cardiomyopathy

A technology for dilated cardiomyopathy and ligustrazine phosphate, applied in the field of medicine, can solve problems such as unreported, achieve strong scientific and innovative effects, improve the structure of intercalated discs, and reduce mitochondrial swelling

Inactive Publication Date: 2009-05-06
INST OF LAB ANIMAL SCI CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Ligustrazine (C 8 h 12 N 2 ) is a known chemical monomer present in many plants such as Ligusticum chuanxiong, ligustrazine phosphate (C8H 12 N 2 ·H 3 PO 4 ·H 2 O, Tetramethylpyrazine Phosphate, TMPP) and its derivative

Method used

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  • Use of ligustrazine phosphate in preparing medicine for treating dilated cardiomyopathy
  • Use of ligustrazine phosphate in preparing medicine for treating dilated cardiomyopathy
  • Use of ligustrazine phosphate in preparing medicine for treating dilated cardiomyopathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Effect of long-term administration of ligustrazine phosphate on the survival rate of model mice with dilated heart disease:

[0019] 1. Animal grouping and administration: identification of cTnT by PCR R141W Transgenic positive mice. The negative mice were used as controls, and the positive mice were evenly divided into a model group and a ligustrazine phosphate administration group according to the results of echocardiography 1.5 months after birth, with 12 animals in each group. Tetramethylpyrazine phosphate (45 mg / kg, approved by the Chinese Medicine H11021964, Beijing Yanjing Pharmaceutical Co., Ltd.) was administered orally for 6 months.

[0020] 2. Survival Analysis: The cTnT R141W In the transgenic dilated cardiomyopathy model, individuals died during the breeding process. We recorded the number of animals that died in each group from the beginning of administration to the end of observation. The number of animals that died in the negative control group was 0, ...

Embodiment 2

[0022] Effects of long-term administration of ligustrazine phosphate on cardiac function and configuration of model mice with dilated heart disease (ultrasound):

[0023] Echocardiography was performed once a month, under tribromoethanol anesthesia, and a small animal ultrasound instrument (Vevo770 small animal ultrasound detection system, Canada) was used to scan the probe at 30 MHz. The long-axis M-ultrasound results of the left ventricle were analyzed by echocardiography. Heart shape and heart function of animals in each group, including BW (body weight, body weight), LVPW; d (thickness of left ventricular posterior wall in diastole), LVPW; s (thickness of left ventricular posterior wall in systole), LVAW; d (diastolic left ventricular anterior wall thickness), LVAW; s (systolic left ventricular anterior wall thickness), LV Mass(AW) (left ventricular weight), Diameter; s (systolic left ventricular diameter), Diameter; d( Diastolic left ventricular diameter), Volume; s (syst...

Embodiment 3

[0028] Effects of Long-term Administration of Ligustrazine Phosphate on the Microstructure of the Heart in Mice with Dilated Cardiac Disease

[0029] (HE and Masson staining):

[0030] 1. Method: fix the heart, paraffin section, conventional HE staining. Masson composite staining solution for 5 minutes, 0.2% acetic acid aqueous solution for a little washing, 5% phosphotungstic acid for 5-10 minutes, 0.2% acetic acid aqueous solution for 5 minutes, bright green staining solution for 5 minutes. Immerse twice in 0.2% acetic acid aqueous solution, dehydrate with absolute ethanol, make xylene transparent, and seal with neutral gum. Observation under a light microscope: collagen fibers are green, muscle fibers are red, and red blood cells are orange.

[0031] 2. Results: Observed under the light microscope, the myocardial fibers in the model group were unevenly hypertrophied, arranged in disorder, and some cells were vacuolated; the nucleus of the myocardial cells was large, deepl...

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Abstract

The invention belongs to the medicine field and provides the application of ligustrazine phosphate used for preparing a medicament for curing dilated cardiomyopathy. The ligustrazine phosphate has the following functions of: reducing the death rate of genetic dilated cardiomyopathy, improving the heart function of the dilated cardiomyopathy and relieving the expansion of the left ventricle when the ligustrazine phosphate is used for a long period; relieving the hypertrophy of the myocardial cells of the dilated cardiomyopathy as well as the hyperplasia of interstitial collagen; relieving the uneven thickness of the myocardial fibers, disorderly arrangement, mitochondrial swelling, cristae fragmentation, sarcoplasmic reticulum expansion and damaged intercalated disc connection of the dilated cardiomyopathy; improving the expression of the ligandin Cx40 of the myocardial cells, improving the expression of Myl4 and Myl7 of a myosin light chain, reducing the expression of Myot as well as reducing the expression of collagenous fibers, Col1a1 and Col3a1.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the application of ligustrazine phosphate as a medicine for treating dilated cardiomyopathy. Background technique [0002] Dilated cardiomyopathy is a myocardial disease mainly characterized by ventricular dilation and impaired myocardial systolic function. The clinical manifestations are progressive heart failure, arrhythmia, thromboembolism, and even sudden death. The prognosis is extremely poor, and the 5-year survival rate Less than 50%. The typical pathological features are dilation of ventricular cavity, thinning of heart wall, and apoptosis of cardiomyocytes. The main etiology is viral myocarditis and gene mutation, accounting for 70% of the incidence of dilated cardiomyopathy. [0003] A variety of mutated genes associated with dilated cardiomyopathy have been found in clinical studies, but most gene mutations can cause HCM and DCM at the same time, while the R141W mu...

Claims

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Application Information

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IPC IPC(8): A61K31/4965A61P9/04A61P9/06
Inventor 张连峰赵海萍秦川李万波
Owner INST OF LAB ANIMAL SCI CHINESE ACAD OF MEDICAL SCI
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