Drug for promoting recovery from chronic spinal cord injury and preparation method and application thereof

A spinal cord injury and drug technology, applied in the field of biomedicine, to achieve the effect of promoting neuron protection and axon regeneration, improving functional recovery, and inhibiting inflammation

Inactive Publication Date: 2020-02-25
周翔
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Methylprednisone therapy should only be used for non-penetrating acute spinal cord injuries 8 hours after injury

Method used

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  • Drug for promoting recovery from chronic spinal cord injury and preparation method and application thereof
  • Drug for promoting recovery from chronic spinal cord injury and preparation method and application thereof
  • Drug for promoting recovery from chronic spinal cord injury and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1 experimental material and method

[0032] 1. Experimental materials:

[0033]1.1 Drug: RGFP966 (provided by Shanghai Yijie Biotechnology Co., Ltd.)

[0034] 1.2 Animals Wild-type mice (C57BL6, provided by the Animal Experiment Middle School of Xi'an Jiaotong University School of Medicine)

[0035] 2. Experimental method

[0036] 2.1 Spinal cord injury model preparation

[0037] Spinal cord contusion model: 4-6 week old wild-type mice (C57BL6, provided by the Animal Experiment Middle School of Xi'an Jiaotong University School of Medicine) were randomly selected, weighed, and anesthetized by isoflurane inhalation. After successful anesthesia, cut off the hair in the operation area, take the prone position, and use iodophor and alcohol to disinfect the operation area. Make a central incision on the back, incision layer by layer, bluntly dissect the paravertebral musculature and bite off T8-9. After fully exposing the T8-9 lamina, gently resect the entire s...

Embodiment 2

[0044] Embodiment 2 Drug Usage and Dosage

[0045] Usage one:

[0046] 1. Drug preparation:

[0047] (1) 100mg RGFP966 was dissolved in 2mL DMSO to prepare a storage solution with a concentration of 50mg / mL

[0048] (2) Configure the carrier solvent, dissolve 30% hydroxypropyl-β-cyclodextrin (2-Hydroxypropyl-β-cyclodextrin) in 100mM sodium acetate (Sodium acetate), adjust the pH to 5.6; the carrier solvent can also be Mix DMSO, PEG300, Tween, and normal saline in sequence, and the volume ratio of the final solution is 5% DMSO, 40% PEG300, 10% Tween80, and 45% normal saline; prepare and use immediately;

[0049] (3) 1 part of storage solution and 49 parts of carrier solution were mixed to obtain an injection solution, and the concentration of RGFP966 was respectively 1 mg / mL.

[0050] 2. Drug injection:

[0051] (1) The RGFP966 treatment group was given an injection solution of 10mL / kg each time, subcutaneously (that is, the dosage of RGFP966 was 10mg / kg)

[0052] (2) The ...

Embodiment 3

[0069] Example 3 High expression of HDAC3 in macrophage / microglia after acute and chronic spinal cord injury

[0070] Firstly, the dynamic expression of HDAC3 was detected by immunohistochemistry at 28 days after spinal cord injury (28dpi). In an in vivo model of dorsal tract transection of spinal cord injury, a marked high expression of HDAC3 was found in the center of the lesion 28 days after injury ( figure 1 a). Temporal analysis showed that HDAC3 upregulation was detectable at 2dpi, peaked at 14dpi, and continued until 28dpi with a slight attenuation ( figure 1 b). In chronic spinal cord injury, HDAC3 was markedly upregulated in the nuclei of CD11b-positive cells when overlaid with CD11b, a cell surface marker of microglia- and monocyte-derived inflammatory macrophages in the central nervous system ( figure 1 c). Thus, different class I HDACs appear to be differentially regulated in different cell types after SCI. Co-immunostaining for HDAC3 and IBA1 confirmed the in...

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Abstract

The invention relates to a drug for promoting recovery from chronic spinal cord injury and a preparation method and application thereof. The technical problem to be solved by the invention is to provide a new option for the treatment of spinal cord injury. The technical scheme of the invention is a drug for promoting recovery from spinal cord injury, and a main active ingredient of the drug is a specific histone deacetylase 3 inhibitor RGFP966. The invention discloses a novel function of RGFP966 treatment by inhibiting HDAC to inhibit inflammatory reaction, promote anti-inflammatory reaction,promote axon regeneration and promote functional recovery after chronic spinal cord injury, thereby indicating a new direction for immunoregulation of spinal cord injury repairing.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a medicine for promoting the recovery of chronic spinal cord injury, a preparation method and application thereof. Background technique [0002] Spinal cord injury is one of the most serious diseases, causing serious sequelae such as paralysis, severe pain and progressive neurological damage. SCI is primarily a direct destruction of spinal cord tissue, including the blood-spinal cord barrier, whereas secondary injury is characterized by inflammation that may lead to reactive gliosis, edema, and cavitation of the spinal cord parenchyma [1] . Spinal cord injury can be divided into three stages: (1) acute (seconds to minutes after injury), (2) secondary (minutes to weeks after injury), (3) chronic (months to weeks after injury). year) [2] . At this stage, there are many kinds of drugs for the treatment of spinal cord injury, but because the regulation mechanism of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/415A61K9/08A61K47/40A61P25/00A61P25/28
CPCA61K9/0019A61K31/415A61K47/40A61P25/00A61P25/28
Inventor 周翔杨琳
Owner 周翔
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