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Polymer material with nerve tissue repair activity, and preparing method and application of polymer material

A technology of polymer materials and nerve tissue, applied in the field of nerve repair, can solve the problems of increasing adverse reactions and side effects of patients, fluctuations in blood drug concentration, complex stent systems, etc., and achieves good biocompatibility, which is beneficial to later clinical application and storage The effect of stability and the simplicity of the bracket system

Active Publication Date: 2019-11-19
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The clinical use of GM1 is mainly administered through peripheral injection. Although exogenous GM1 is fat-soluble and can pass through the blood-brain barrier, pharmacokinetic studies have confirmed that GM1 after injection into the body is mainly absorbed through the liver, and the central nervous system. The content in the system is very small, only about 20% enters the brain, spinal cord and other parts to play a role, and the GM1 content in the central nervous system will not reach the peak 8-16 hours after administration. The required drug concentration greatly increases the adverse reactions and side effects of patients
[0006] CN102641281A discloses a monosialotetrahexosyl ganglioside sodium for injection and its preparation method, mainly aiming at the problem of GM1 being treated clinically with long-term and high-dose repeated administration of spinal cord injury through the peripheral route. Sodium monosialotetrahexosylganglioside microspheres (including GM1, gelatin and PLGA) to achieve sustained and stable release of drugs and solve the problem of blood drug concentration fluctuations caused by conventional preparations
[0008] The above existing technologies have not solved the problems of low survival rate of transplanted cells in the presence of loaded cells and active factors on nerve repair scaffolds, easy inactivation of active factors, insufficient local concentration, and too complicated scaffold system, nor have they solved the central nervous system problems caused by GM1. The problem of little effective content in the system

Method used

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  • Polymer material with nerve tissue repair activity, and preparing method and application of polymer material
  • Polymer material with nerve tissue repair activity, and preparing method and application of polymer material
  • Polymer material with nerve tissue repair activity, and preparing method and application of polymer material

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] In this example, a hydrolyzate of monosialotetrahexosyl ganglioside (GM1) (expressed as LysoGM1) was prepared and its hydrolysis efficiency was determined. The preparation method is as follows:

[0071] (1) Weigh 0.08g of taurodeoxycholic acid hydrate (TDC), calcium chloride (CaCl 2 ) 10.1g in 20mL of 35mM sodium acetate buffer solution (pH adjusted to 5.8);

[0072] (2) Weigh 100mg of GM1 and add it to the above buffer solution, fully stir to dissolve;

[0073] (3) Transfer to a 50 mL centrifuge tube after fully dissolving, add 15 μL of glycosphingolipid N-deacylase (concentration: 5 U / mL), and place in a constant temperature (37°C) shaking box for shaking reaction for 12 hours;

[0074] (4) Centrifuge at 12000r / min for 5min, take the supernatant and freeze-dry it for storage.

[0075] The hydrolysis efficiency of GM1 is measured by RP-HPLC. The maximum absorption wavelength of GM1 is about 197nm. Since there is more interference below 200nm, 205nm is selected as the...

Embodiment 2

[0079] This example prepares a polymer material with nerve tissue repair activity, which is represented by PLGA-LysoGM1 (the schematic diagram of the synthesis process is shown in figure 2 shown), and analyzed by IR spectroscopy and NMR. Its preparation method is as follows:

[0080] (1) Take by weighing 50 mg of the hydrolyzate LysoGM1 prepared in Example 1, transfer to 10 mL of anhydrous DMF for dissolving, then weigh 1 g of PLGA solid (the number average molecular weight is 8 kDa, the mole of lactic acid structural unit and glycolic acid structural unit Ratio is 75:25), after adding, stir fully to make it dissolve completely;

[0081] (2) Weigh 10.6 mg (hydroxybenzotriazole) HOBt into the above system, add 15.3 μL tributylamine solution, and stir vigorously at room temperature for 2 hours. The molar ratio of LysoGM1 to HOBt, tributylamine, and PLGA is about 1:1.8:1.5:0.3;

[0082] (3) Slowly add the reaction solution dropwise into pre-cooled distilled water (at a temper...

Embodiment 3

[0087] In this example, an engineering scaffold with nerve tissue repairing activity was prepared and observed with a scanning electron microscope. Its preparation method is as follows:

[0088] (1) Said that 500mg of PLGA-LysoGM1 prepared in Example 2 was dissolved in the mixed solution of chloroform:DMF (85:15 mass ratio), and the concentration was 15wt%. Stir at 25°C for 24 hours to make it a uniform solution, and use an ultrasonic oscillator to remove bubbles in the solution;

[0089] (2) Draw the spinning solution into the syringe and place it on the microsampler. Connect the high-voltage DC power supply to the needle of the syringe. The needle type of the syringe is 22G and the inner diameter is 0.41mm. Evenly cover the surface of the circular drum receiver (diameter 15cm) with tinfoil, and ground the drum receiver;

[0090] (3) The set voltage is 15kV, the flow rate of the injector is 1mL / h, the rotating drum receiver is received (rotating speed is 0r / min), and the te...

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Abstract

The invention relates to a polymer material with nerve tissue repair activity, and a preparing method and application of the polymer material. The polymer material is prepared from a hydrolysis product of monosialotetera-hexosyl ganglioside and a polylactic acid-glycolic acid copolymer (PLGA) which are connected through amido bonds, wherein the hydrolysis product of monosialotetera-hexosyl ganglioside is shown as a formula (I) (please see the specifications for the formula (I)). The polymer material has good biocompatibility, degradability and the mechanical property. Through the polymer material, the PLGA does not need to be loaded with various repair-promoting related factors, thus the nerve repair function can be achieved, thus a stent system prepared through the polymer material is simpler, later clinical application and storage are facilitated, and the polymer material is a bioactive material with clinical application prospects.

Description

technical field [0001] The invention belongs to the technical field of nerve repair, and specifically relates to a polymer material and its preparation method and application, in particular to a polymer material with nerve tissue repair activity and its preparation method and application. Background technique [0002] Traumatic brain injury (TBI) usually refers to the tissue defect, nerve connection rupture and corresponding function loss caused by the strong impact of the head on the brain tissue under the action of external mechanical stress. TBI not only causes structural loss of brain tissue, but also forms a secondary injury microenvironment in the injured area that is not conducive to neuronal recovery. The self-repair ability of brain tissue after TBI is extremely limited, and TBI treatment has become a difficult point in clinical treatment. [0003] Currently, the main strategies for post-TBI treatment include neurotrophic factor therapy, stem cell transplantation t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/18A61L27/54D01D5/00D01F6/92C08G63/91
CPCA61L27/18A61L27/54A61L2300/232A61L2300/412A61L2430/32C08G63/912D01D5/0038D01D5/0076D01D5/0092D01F6/92C08L67/04
Inventor 唐为王亚州房飞
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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