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Application of inhibitor and pharmaceutical composition

A technology of inhibitors and compositions, which can be used in drug combinations, antipyretics, anti-inflammatory agents, etc., and can solve problems such as unclear mechanism of action

Pending Publication Date: 2022-04-01
SHENZHEN INST OF ADVANCED TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether inhibition of the Wnt / β-catenin signaling pathway has a therapeutic effect on discogenic pain, and the underlying mechanism remains unclear.

Method used

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  • Application of inhibitor and pharmaceutical composition
  • Application of inhibitor and pharmaceutical composition
  • Application of inhibitor and pharmaceutical composition

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Construction of transgenic mice: β-catenin(ex3) flox / flox Mice were crossed with Col2-CreER mice to construct chondrocyte β-catenin targeting endplate and annulus fibrosus Act mice, and the mouse genotype was identified by genotyping. The cells expressing Col2 in this mouse will have abnormal accumulation of β-catenin protein and activate the Wnt / β-catenin signaling pathway. This mouse model mimics pathological conditions in which disc cells overexpress β-catenin.

[0084] A mouse model of intervertebral disc degeneration was constructed by resection of the supraspinous and medial spinous ligaments.

[0085] In vitro experiments, the C28 / I2 human chondrocyte cell line was used as a cell model, in which transfection of TCF7 plasmid can increase the expression level of TCF7 in C28 / I2 chondrocytes; To activate Wnt / β-catenin signaling pathway.

[0086] In vitro experiments, the effective concentration of BIO was 1 μM, and the treatment time was 12 hours; the effective c...

Embodiment 2

[0093] Nerve compression caused by intervertebral foraminal stenosis is an important cause of numbness and low back pain caused by intervertebral disc degeneration. In order to evaluate the effect of abnormal activation of β-catenin signaling pathway on the intervertebral foramina of mice, we reconstructed the mouse spine by μCT, the results are as follows Figure 2A shown.

[0094] Depend on Figure 2A It can be seen that the β-catenin overexpression transgenic mice decreased the diameter of the intervertebral foramina and increased the formation of osteophytes. This may cause compression of the spinal nerve passing through the intervertebral foramen, resulting in allodynia in β-catenin-overexpressing transgenic mice.

[0095] In order to clarify the influence of abnormal activation of β-catenin signaling pathway on the pathological process of mouse intervertebral disc degeneration, we used safranin O fast green staining for β-catenin Act Mouse [i.e. β-catenin(ex3) Col2ER...

Embodiment 3

[0098] At present, the mechanism of pain has not been fully studied. It is widely believed that after the nerve endings are subjected to various noxious stimuli, they are transmitted to the center through the conduction system, causing nociception. The dorsal root ganglion (DRG) plays an important role in low back pain signal transduction, so we used immunofluorescence and qPCR to evaluate the activation level of DRG near the L4 / L5 lumbar spine of β-cateninAct mice, and obtained Figure 3A , Figure 3B and Figure 3C .

[0099] Depend on Figure 3A It can be seen that the fluorescence signals of PGP9.5 and Tuj1 in the dorsal root ganglia of the β-catenin overexpression transgenic mice were significantly stronger than those of the dorsal root ganglia of the Cre negative control group mice. This suggests that β-catenin overexpression transgenic mice have a higher degree of activation of dorsal root ganglia.

[0100] Depend on Figure 3B It can be seen that the mRNA expressi...

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Abstract

The invention discloses application of an inhibitor in preparation of a medicine for treating discogenic pain and a medicine composition. The pharmaceutical composition is a beta-catenin protein and TCF7 transcription factor binding inhibitor and / or a Wnt / beta-catenin signal channel inhibitor. In combination with data of an embodiment part, the beta-catenin protein and TCF7 transcription factor binding inhibitor and / or the Wnt / beta-catenin signal channel inhibitor can achieve the effect of treating the discogenic pain based on the inhibition of the Wnt / beta-catenin signal channel.

Description

technical field [0001] The invention relates to the field of treatment of geriatric diseases, in particular to the application of an inhibitor and a pharmaceutical composition. Background technique [0002] Discogenic pain mainly refers to low back pain caused by disc degeneration. In a broad sense, discogenic neck pain can include all neck, shoulder and arm pain caused by intervertebral disc disease, but many pains caused by it have corresponding disease names, such as cervical disc herniation, cervical disc degeneration and stenosis, and cervical spondylosis. In recent years, cervical discogenic pain (cervical discogenic pain) specifically refers to the pain caused by the internal disorder of the intervertebral disc, without radiating pain and segmental nerve dysfunction, and does not involve the adjacent spinal cord, nerve roots, and facet joints. Discogenic neck pain is one of the common causes of chronic, intermittent neck and shoulder pain. [0003] Some clinical stu...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K31/4439A61P25/00A61P29/00
CPCA61P29/00A61K38/17A61P25/00A61K31/4439
Inventor 陈棣陆克
Owner SHENZHEN INST OF ADVANCED TECH
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