Application of SEW2871 in preparation of medicine for treating muscular dystrophy

A technology of 1. SEW2871, muscular dystrophy, applied in the field of medicine, can solve the problems of gene therapy methods in the research stage, adverse reactions of patients, etc., to achieve the effect of improving muscle weakness and/or muscle atrophy, and reducing inflammation

Pending Publication Date: 2022-03-11
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Duchenne muscular dystrophy is a genetic disease caused by gene mutations. Gene therapy may eventually be an effective way for Duchenne muscular dystrophy, but so far gene therapy is still in the research stage
At present, the first-line treatment for Duchenne muscular dystrophy is hormone combined nursing. Although hormone therapy has a certain effect, it brings a series of adverse reactions to patients, including: gastrointestinal tract reactions, obesity, etc.

Method used

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  • Application of SEW2871 in preparation of medicine for treating muscular dystrophy
  • Application of SEW2871 in preparation of medicine for treating muscular dystrophy
  • Application of SEW2871 in preparation of medicine for treating muscular dystrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] 1- Construction of animal model:

[0021] mdx mice are DMD gene defects, leading to the absence of dystrophin protein, a well-recognized model mouse for the study of Duchenne / Bein muscular dystrophy. Compared with the wild control group, mdx mice had abnormal muscle tissue morphology; markers of muscle degeneration, serum levels of creatine kinase and lactate dehydrogenase increased; a large number of macrophages accumulated in muscle tissue, accompanied by fibrosis and The occurrence of necrosis. The experimental animals used in the present invention are mdx transgenic mice named (C57BL / 10ScSnJNju-DmdDMD / Nju), purchased from Nanjing Jicui Yaokang Company.

[0022] 2- Animal grouping and administration

[0023] The present invention administers SEW2871 to mdx mice by intragastric administration at a dose of 1 mg / kg / day, and feeds them for 42 days. On the 40th day of administration, the forelimb muscle grip strength of the mice was measured, the rod hanging time of th...

Embodiment 2

[0041] Gait analysis: the gait analysis and statistics of the mdx mice after the 41st day of administration in Example 1 were carried out using the ink method. The stride length and stride width of the front and hind limbs of mice in each group were recorded respectively. The average value of each test was taken 3 times, and the results are shown in Table 4.

[0042] Table 4mdx mouse gait experiment statistical results

[0043] group normal group DMD model group SEW2871 treatment group Forelimb stride length (cm) 6.5±0.5 5.1±0.7 *

5.7±0.3 #

Hindlimb stride length (cm) 6.9±0.5 5.3±0.6 *

6.8±0.8 #

Forelimb stride width (cm) 2.0±0.3 1.7±0.1 *

2.0±0.3 #

Hind leg width (cm) 2.6±0.3 2.9±0.5 *

2.5±0.3 #

[0044] * P# P<0.05 compared with DMD model group.

[0045] The results showed that the forelimb step width of the mice in the DMD model group became narrower, the hindlimb step length became shorter and t...

Embodiment 3

[0047] After 42 days of administration, the mdx mice in Example 1 were euthanized on the 43rd day after overnight fasting for 12 hours, blood was taken from the inguinal vein, centrifuged at 3500 rpm for 10 minutes, and the upper serum was taken to measure serum creatine kinase (CK) and lactic acid Dehydrogenase (LDH) content. Then the gastrocnemius, tibialis anterior muscle, and diaphragm were dissected and quickly frozen in liquid nitrogen, and transferred to a minus 80 refrigerator for later use. Serum CK, LDH content and tibialis anterior muscle weight are shown in Table 5.

[0048] Table 5 mdx mouse tibialis anterior muscle weight

[0049] group normal group DMD model group SEW2871 treatment group CK(U / L) 1942.5±550.3 18900.0±7145.6 *

16971.7±5364.5 #

LDH(U / L) 542.5±196.8 5824.3±2019.8 *

2452.9±607.6 #

Tibialis anterior muscle weight (mg) 52.2±3.9 63.3±6.8 *

57.7±5.5 #

[0050] * P# P<0.05 compared with DMD ...

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Abstract

The invention discloses application of SEW2871 in preparation of a medicine for treating muscular dystrophy, and belongs to the field of medicine. The influence of SEW2871 on myasthenia and amyotrophy caused by muscular dystrophy is systematically studied from the aspects of pharmacodynamics, behavioristics, molecular biology and the like, and the result shows that SEW2871 can reverse the deficiency of muscle fibers and enhance the strength and function of skeletal muscles. The SEW2871 can relieve skeletal muscle inflammation and fibrosis and increase the gripping power of skeletal muscle.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of SEW2871 in the preparation of medicine for treating muscular dystrophy. Background technique [0002] SEW2871( figure 1 ) is an orally bioavailable S1P receptor modulator with potential anti-inflammatory and immunomodulatory activities. After oral administration, SEW2871 selectively targets and binds to S1PR1 on lymphocytes, and induces S1PR1 internalization and degradation. This causes lymphocytes to become sequestered in the lymph nodes. By preventing lymphocyte efflux, SEW2871 reduces the number of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues, which prevents lymphocyte-mediated immune responses and may reduce inflammation. S1PR1 is a G protein-coupled receptor that plays a key role in the migration of lymphocytes. [0003] Duchenne muscular dystrophy is a genetic disease caused by gene mutation. Gene therapy may event...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4245A61P21/04A61P21/00
CPCA61K31/4245A61P21/04A61P21/00
Inventor 江振洲黄小菲俞沁玮范书生洪晖涛赖竹兰李春杰
Owner CHINA PHARM UNIV
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