CN-121971486-A - Spinal cord injury repair nano system based on metal polyphenol coordination self-assembly

Abstract

The invention discloses a metal polyphenol coordination self-assembly-based spinal cord injury repair nano system, which belongs to the technical field of medicines, and the nano system preparation method comprises the steps of self-assembling Ce 3+ and kaempferol in a PEG-8000 solution system, and self-assembling nano drug delivery system (CEKAEMNCS) is used for reducing oxidative stress reaction after spinal cord injury by scavenging oxygen free radicals and regulating inflammatory reaction, remodelling extracellular matrix so as to promote the repair of spinal cord injury, and provides a new drug source for the auxiliary treatment of spinal cord injury drugs.

Inventors

• MA YANMING
• ZHAO YUQI
• LIU SHENGHANG
• HU HUIMIN
• ZHU LEI
• JU CHENG
• LUO RONGJIN

Assignees

• 西安市红会医院（西安市骨科研究所）

Dates

Publication Date

20260505

Application Date

20260123

Claims (10)

1. 1. The preparation method of the spinal cord injury repair nano system based on metal polyphenol coordination self-assembly is characterized by comprising the step of self-assembling Ce 3+ and kaempferol in a PEG-8000 solution system.
2. 2. The method for preparing a metal polyphenol coordination self-assembly-based spinal cord injury repair nano system according to claim 1, wherein the nano drug delivery system preparation process comprises the following steps: S1, dissolving PEG-8000 and Ce (NO 3 ） 3 ·6H 2 O in ultrapure water, adding kaempferol, and performing self-assembly under the stirring effect; s2, centrifuging and freeze-drying to obtain the product.
3. 3. The preparation method of the metal polyphenol coordination self-assembly-based spinal cord injury repair nano system according to claim 1 or 2, wherein the mass concentration ratio of PEG-8000, ce 3+ and kaempferol is 1:2.36:0.25.
4. 4. The method for preparing the metal polyphenol coordination self-assembly-based spinal cord injury repair nano system according to claim 2, wherein the stirring is performed by magnetic stirring at a speed of 500rpm for 20 minutes.
5. 5. The method for preparing a metal polyphenol coordination self-assembled spinal cord injury repair nano system according to claim 2, wherein the centrifugation process comprises centrifugation for 10 minutes under a centrifugal force of 8000 times of gravity acceleration.
6. 6. A metal polyphenol coordination self-assembled spinal cord injury repair nano system, which is characterized by being prepared by the preparation method of any one of claims 1-5.
7. 7. The use of the metal polyphenol coordination self-assembly-based spinal cord injury repair nano system according to claim 6 in the preparation of a medicament for treating spinal cord injury.
8. 8. The use of claim 7, wherein the treatment comprises scavenging oxygen radicals, modulating inflammatory responses, remodeling extracellular matrix to reduce oxidative stress following spinal cord injury.
9. 9. A medicament comprising the metal polyphenol coordination self-assembled spinal cord injury repair nanosystem of claim 6.
10. 10. The medicament according to claim 9, wherein the medicament is an injection.

Description

Spinal cord injury repair nano system based on metal polyphenol coordination self-assembly Technical Field The invention belongs to the technical field of medicines, and particularly relates to a spinal cord injury repair nano system based on metal polyphenol coordination self-assembly. Background Spinal cord injury (SpinalCordInjury, SCI) is a serious traumatic disease of the central nervous system, and refers to a pathological state that the spinal cord tissue structure is destroyed due to external mechanical forces such as traffic accidents, high falling, sports injury and the like directly or indirectly acting on the spinal column, so that the motor, the sensory and the autonomic nerve functions below the injury plane are temporarily or permanently lost. Because of the limited self-repairing capability of the central nervous system, SCI not only has extremely high disability rate, but also often accompanies paraplegia, fecal incontinence and various complications, brings great physical and psychological pain to patients, and simultaneously causes heavy economic burden and medical care pressure to families and society. From the pathophysiological mechanism, spinal cord injury is a dynamically evolving process, mainly comprising two stages, primary and secondary. The primary injury is caused by the instant action of external force, and is often accompanied by vertebral fracture, dislocation and disc herniation, so that physical contusion, axon fracture, vascular fracture and hemorrhage of spinal cord tissues are caused. After the primary injury occurs, a complex cascade of reactions, secondary injury, is triggered rapidly. This stage involves a number of pathological processes such as local microcirculation disorders (ischemia/hypoxia), blood-spinal barrier disruption, severe inflammatory reactions, excitatory amino acid toxicity, imbalance in ion homeostasis, and oxidative stress. Among them, the oxidative stress reaction is particularly critical, and researches show that after SCI occurs, the active oxygen (ReactiveOxygenSpecies, ROS) level in the damaged tissue is rapidly increased, and the signal channels such as MAPK, NF-kappa B, HIF-1 and the like are obviously activated. Excessive ROS not only directly attacks cell membrane lipid to cause lipid peroxidation and damage protein and DNA structure, but also induces apoptosis and necrosis of neurons and glial cells, further expands the damage range and forms a microenvironment (inhibitory microenvironment) which is unfavorable for nerve regeneration. Therefore, aiming at the secondary injury stage, particularly effectively scavenging active oxygen free radicals generated in the explosive manner in the acute stage of SCI, inhibiting oxidative stress reaction, and remodelling the oxidation-reduction balance of the injury part, the method has become a key treatment strategy for blocking the deterioration of the secondary injury, saving dying neurons and promoting the recovery of nerve functions. Currently, drug development for oxidative stress mechanisms has focused mainly on traditional antioxidants (e.g., vitamin C, vitamin E, etc.) and some naturally active small molecules. However, the traditional small molecule antioxidants often have the defects of low bioavailability, short half-life, difficult effective penetration of the Blood Spinal Cord Barrier (BSCB), poor targeting and the like, so that the clinical treatment effect is not ideal. In recent years, with the development of nanomedicine, functional nanomaterials having antioxidant activity have been attracting attention due to their unique physicochemical properties. Wherein, the metal-based nano material (such as cerium oxide nano particles and the like) can circularly remove ROS due to the fact that the metal-based nano material has mimic enzyme activities (such as superoxide dismutase SOD and catalase CAT activities), and has great application potential. However, single inorganic metal nano particles often have the problems of complex synthesis process, improved biocompatibility, limited drug carrying capacity and the like, and single natural antioxidant small molecule drugs have the challenges of poor stability, easy metabolism and the like. How to develop a novel nanometer treatment platform which can effectively remove ROS and realize stable drug delivery and has good biological safety is a technical problem to be solved in the current spinal cord injury treatment field. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a spinal cord injury repair nano system based on metal polyphenol coordination self-assembly, which solves the problems in the prior art. The aim of the invention can be achieved by the following technical scheme: the preparation method of the spinal cord injury repair nano system based on metal polyphenol coordination self-assembly comprises the step of self-assembling Ce 3+ and kaempferol in a PEG-8000 solution system. Further, th