A kind of neurotrophin sustained-release coacervate for curing the peripheral nerve injury and its application thereof

A technology for neurotrophic factors and peripheral nerve injury, which is applied to nervous system diseases, medical preparations containing non-active ingredients, medical preparations containing active ingredients, etc., to achieve wide and cheap raw material sources, high encapsulation rate, and remarkable therapeutic effect Effect

Inactive Publication Date: 2017-01-04
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But for finding or synthesizing an ideal nerve repair material: that is, it has good mechanical properties and spatial structure, provides the best physical, chemical and biological microenvironment for nerve regeneration, and can realize fast, simple, safe and convenient nerve anastomosis. good prognosis multiple purposes, there is still a certain gap

Method used

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  • A kind of neurotrophin sustained-release coacervate for curing the peripheral nerve injury and its application thereof
  • A kind of neurotrophin sustained-release coacervate for curing the peripheral nerve injury and its application thereof
  • A kind of neurotrophin sustained-release coacervate for curing the peripheral nerve injury and its application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1. Establishment of an animal model of peripheral nerve injury

[0029] a. Rat sciatic nerve crush injury model

[0030] SPF grade Wistar rats were selected and raised in separate cages in the school experimental animal center, kept at room temperature of 22°C, with natural light, and free to eat. Rats were anesthetized by intraperitoneal injection of 10% chloral hydrate successively, and the sciatic nerve of the right leg was incised, and the sciatic nerve was separated with a glass minute needle. For severe contusions, the muscles and skin were sutured with non-invasive fine thread (5 / 0) and disinfected with povidone iodine. The sham operation group only needs to incision and suture. The temperature was maintained at 37°C throughout the operation to prevent the death of the modeled Wistar rats due to hypothermia.

[0031] b. Rat sciatic nerve transection model

[0032]SPF grade Wistar rats were selected and raised in separate cages in the school experiment...

Embodiment 2

[0033] Example 2. Preparation of slow-release aggregates of neurotrophic factors

[0034] a. Synthesis of PEAD:

[0035] First, 1000 mg of ethylene glycol diglycidyl ether (EGDE), 1340 mg of aspartic acid (ASP) protected by tert-butoxycarbonyl (t-BOC) and 50 mg of tertiary ammonium bromide (TBAB) were put into 10 mL After adding 0.6mL of dimethylformamide (DMF) to the microwave reaction flask and mixing it well, heat it in a microwave reactor at 120°C for 20min to obtain a viscous orange liquid; then add 5mL of trifluoro Acetic acid (TFA) and 20 mL of dichloromethane (DCM) were stirred at room temperature for 2 h to extract the intermediate polyethylene-aspartic acid glyceride (PED); then 770 mg of ASP, 323 mg of N-hydrosuccinimide (NHS), 753 mg of di Cyclohexylcarbodiimide (DCC) was added to 35mL of DMF solution and stirred in the glove box for 2h to obtain a milky orange liquid with precipitation, which was sucked into a 50mL centrifuge tube and placed in a high-speed centr...

Embodiment 3

[0047] Embodiment 3. animal administration and curative effect evaluation

[0048] After suturing the muscles and skin of Wistar rats with sciatic nerve crush injury or transverse injury model, the slow-release aggregates of neurotrophic factors prepared by each experimental group and control group in Table 1 were delivered into the injured sciatic nerve area in time through a 30G needle .

[0049] The evaluation indicators for the effect of nerve restoration are as follows:

[0050] a. Behavior: Wistar rats after sciatic nerve injury were tested for motor function and sensory function by footstep imprinting and hot plate test respectively, and the time was 1st, 2nd, 3rd and 4th weeks after administration;

[0051] b. Histomorphology: After 1 month of drug treatment, the rats in each group were killed, the injured sciatic nerve was collected, pathological sections were made, and HE staining, Massion staining and transmission electron microscopy were performed;

[0052] c. Ex...

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Abstract

The invention relates to a neurotrophin sustained-release coacervate for curing peripheral nerve injury and its application thereof. The neurotrophin sustained-release coacervate includes polyethylene arginine aspartic acid glyceraldehyde (PEAD), glycosaminoglycans (GAGs) and neurotrophic factors (NTFs). By changing the different ratio of components and the type of NTFs, it can improve the performance of the sustained-release coacervate. The preparation process of the invention-neurotrophin sustained-release coacervate is simple, the drug-loading is large, the stability is good, which is easy to be degraded. This invention is safe and has no side effect, and it has remarkable long lasting sustained-release effect, so as to satisfy the requirements of biomaterials for repairing peripheral nerve injury ideally.

Description

technical field [0001] The invention relates to a neurotrophic factor slow-release aggregate for treating peripheral nerve injury and its application, in particular to a slow-release aggregate loaded with basic cell-forming growth factor and nerve growth factor and its application. Background technique [0002] Degenerative disease is a serious and disabling condition, while peripheral nerve damage is mainly caused by motor vehicle accidents, tumors, congenital deformities, compressions or contusions. Nerve damage manifests as partial or complete loss of motor nerves, sensory nerves, and autonomic nerve functions. One of the reasons for its difficulty in healing is the decrease in the synthesis and secretion of growth factors. There are many ways to repair nerve damage, and the common ones are autologous transplantation repair technology and genetic engineering pipeline technology. Clinically, autologous nerve transplantation is widely used to bridge peripheral nerve defect...

Claims

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Application Information

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IPC IPC(8): A61K38/18A61K9/16A61K47/36A61K47/32A61P25/02A61P17/02A61P9/10
CPCA61K38/185A61K9/0002A61K9/1635A61K9/1652A61K38/1825A61K38/1858A61K38/1866A61K2300/00
Inventor 肖健李锐邹双张宏宇吴疆王亚冬李校堃
Owner WENZHOU MEDICAL UNIV
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