Application of ligustrazine nitrone compound in the preparation of prevention and/or treatment of muscular dystrophy diseases

A technology of ligustrazine nitrone and compounds, which is applied in the field of application of ligustrazine nitrone compounds in the prevention and treatment of muscular dystrophy diseases, can solve problems such as exceeding the threshold of cost-benefit ratio, delay the process of disease deterioration, and increase profits /hazard ratio, efficacy-enhancing effects

Active Publication Date: 2022-03-25
GUANGZHOU MAGPIE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Both drugs cost more than a predetermined cost-benefit ratio threshold

Method used

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  • Application of ligustrazine nitrone compound in the preparation of prevention and/or treatment of muscular dystrophy diseases
  • Application of ligustrazine nitrone compound in the preparation of prevention and/or treatment of muscular dystrophy diseases
  • Application of ligustrazine nitrone compound in the preparation of prevention and/or treatment of muscular dystrophy diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Construction and grouping of embodiment 1.DMD model mice

[0059] (1) Establishment of animal model of Duchenne muscular dystrophy

[0060] Entrusted Nanjing University-Nanjing Institute of Biomedicine to construct the gRNA of the mouse Dmd gene, using CRISPR / Cas9 technology and blastocyst injection technology to target Exon4 of the mouse Dmd gene, and screen for mouse models that can cause frameshift mutations in the Dmd gene.

[0061] (2) Animal grouping and administration

[0062] The mice were kept in the SPF animal laboratory of the Experimental Animal Center of Sanyuanli Campus, Guangzhou University of Traditional Chinese Medicine. Free access to water and food.

[0063]

[0064] Administration method: The animals in each group were administered by intragastric administration for 24 weeks from the age of 8 weeks, and different doses of TBN were intragastrically administered twice a day; the positive control drug deflazacort was administered intraperitoneally,...

Embodiment 2

[0065] Example 2. Effects of TBN on motor coordination ability and motor ability of DMD mice.

[0066] In order to evaluate the improvement of TBN on the motor behavior function of DMD mice, after the administration started, the pole climbing time and open field movement distance of the mice in each group were measured every 4 weeks for 24 consecutive weeks.

[0067] The pole-climbing test can assess the movement and coordination of the mouse limbs. Make a wooden pole with a length of about 50cm and a diameter of about 1cm. The pole is wrapped with gauze to increase friction. The wooden pole is placed vertically on a horizontal table, and the mouse is gently placed on the top of the pole with its head down. The mouse crawls down autonomously without being driven by external force, and the time for the mouse to climb from the top of the pole to the platform at the bottom is recorded. (rod climbing time). Continuous training for 3 days before each measurement, 2 times a day, the...

Embodiment 3

[0069] Embodiment 3.TBN significantly improves the content of SOD in DMD mouse serum

[0070] At the end of the experiment, blood was taken from the abdominal aorta of the anesthetized mice, and after standing for 1 hour, the supernatant was collected by centrifugation at 3000rmp for 10 minutes, and the content was measured by an automatic biochemical analyzer according to the instructions of the SOD kit. Research results such as image 3 As shown, compared with the DMD model group, the 30mg / kg TBN group significantly increased the content of SOD in the serum, and the therapeutic effect was better than that of the positive drug deflazacort.

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Abstract

The invention discloses the application of a ligustrazine nitrone compound in the preparation of drugs for preventing and / or treating muscular dystrophy diseases, wherein the ligustrazine nitrone compound is a compound having a structure represented by general formula (I) or its pharmaceutical Acceptable salt. The experimental results show that the ligustrazine nitrone compound of the present invention can significantly improve the motor dysfunction of the Duchenne muscular dystrophy model mice caused by the frameshift mutation of the Duchenne muscular dystrophy (DMD) gene, improve exercise capacity, and delay the disease progression; It can also significantly reduce the degree of atrophy and fibrosis of gastrocnemius muscle, diaphragm muscle, and myocardial muscle in Duchenne muscular dystrophy model mice. Therefore, the ligustrazine nitrone compound can be made into various dosage forms with drug carriers for the prevention and treatment of muscular dystrophy diseases.

Description

[0001] This application is the application date of October 09, 2019, the application number is: 201910953423.8, and the invention name is "Application of Ligustrazine Nitron Compounds in the Preparation of Prevention and / or Treatment of Muscular Dystrophy Diseases". Divisional application. technical field [0002] The invention belongs to the technical field of medicines, and in particular relates to the application of a ligustrazine nitrone compound in the prevention and treatment of muscular dystrophy. Background technique [0003] Duchenne muscular dystrophy (DMD) is the most common type of muscular dystrophy and is an X-linked recessive genetic disease. Due to a lack of the dystrophin protein, which is critical to muscle fiber function, the patient's muscle cells do not remain intact, leading to disease. The disease is characterized by progressive atrophy and weakness of the proximal skeletal muscles of the extremities, pseudohypertrophy of the gastrocnemius muscle of t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4965A61K45/06A61P21/00A61P21/04
CPCA61K31/4965A61K45/06A61P21/00A61P21/04
Inventor 刘伟孙业伟王玉强
Owner GUANGZHOU MAGPIE PHARMA
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