Preparation method for multicore-single shell microsphere sustained-release system with embedded GDNF

A microsphere and multi-core technology, applied in the direction of nervous system diseases, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of reducing the pH value of the surrounding microenvironment and limiting the regeneration of peripheral nerves, etc., to achieve Improve the effect of acidic microenvironment

Active Publication Date: 2018-05-18
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Secondly, PLGA microspheres produce a large amount of acidic degradation products during the degradation process, such as lactic acid, glycolic acid, etc., which not only denature, aggregate and chemically degrade the embedded protein drugs, but also reduce the pH value of the surrounding microenvironment. This has many negative effects, limiting the regeneration of peripheral nerves

Method used

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  • Preparation method for multicore-single shell microsphere sustained-release system with embedded GDNF
  • Preparation method for multicore-single shell microsphere sustained-release system with embedded GDNF
  • Preparation method for multicore-single shell microsphere sustained-release system with embedded GDNF

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] At 2°C, 60 μL LGDNF solution (0.1 mg / mL concentration), 100 mg docusate sodium and 7 mg human serum albumin were dissolved in 0.5 mL distilled water to prepare the inner aqueous phase W 1 ; 0.6g PLGA was dissolved in 6mL dichloromethane to prepare the oil phase O1 ; Mix 0.6mg polysorbate 80 with 60mL water evenly to prepare the outer layer of water phase W 2 ; the inner water phase W 1 Dispersed in the oil phase O 1 In the process, use an ultrasonic cell pulverizer to ultrasonically disperse for 10 s, and then pause for 10 s; repeat this process twice to obtain the primary emulsion W 1 / O 1 , the output power of the ultrasonic cell pulverizer is 100W, and the working frequency is 15kHz; the colostrum W 1 / O 1 Added to the outer aqueous phase W 2 In the process, the ultrasonic cell pulverizer was used to ultrasonically disperse for 10 s, and then paused for 10 s. This process was repeated twice to prepare a two-layer final emulsion W 1 / O 1 / W 2 , the output powe...

Embodiment 2

[0104] At 2°C, 70 μL LGDNF solution (0.1 mg / mL concentration), 105 mg docusate sodium and 7 mg human serum albumin were dissolved in 0.5 mL distilled water to prepare the inner aqueous phase W 1 ; 0.7g PLGA was dissolved in 6mL dichloromethane to prepare the oil phase O 1 ; Mix 0.6mg of polysorbate 80 with 62mL of water evenly to prepare the outer layer of water phase W 2 ; the inner water phase W 1 Dispersed in the oil phase O 1 In the process, use an ultrasonic cell pulverizer to ultrasonically disperse for 11s, and then pause for 11s; repeat this process twice to obtain the primary emulsion W 1 / O 1 , the output power of the ultrasonic cell pulverizer is 110W, and the working frequency is 16kHz; the colostrum W 1 / O 1 Added to the outer aqueous phase W 2 In the process, the ultrasonic cell pulverizer was used to ultrasonically disperse for 11s, and then paused for 11s. This process was repeated twice to prepare a two-layer final emulsion W 1 / O 1 / W 2 , the output ...

Embodiment 3

[0108] At 3°C, 80 μL LGDNF solution (0.1 mg / mL concentration), 110 mg docusate sodium and 7.5 mg human serum albumin were dissolved in 0.5 mL distilled water to prepare the inner aqueous phase W 1 ; 0.8g PLGA was dissolved in 6mL dichloromethane to prepare the oil phase O 1 ; Mix 0.6mg of polysorbate 80 with 65mL of water evenly to prepare the outer layer of water phase W 2 ; the inner water phase W 1 Dispersed in the oil phase O 1 In the process, use an ultrasonic cell pulverizer to ultrasonically disperse for 13s, and then pause for 13s; repeat this process twice to obtain the primary emulsion W 1 / O 1 , the output power of the ultrasonic cell pulverizer is 130W, and the working frequency is 18kHz; the colostrum W 1 / O 1 Added to the outer aqueous phase W 2 In the process, the ultrasonic cell pulverizer was used to ultrasonically disperse for 13s, and then paused for 13s. This process was repeated twice to prepare a two-layer final emulsion W 1 / O 1 / W 2 , the outpu...

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Abstract

The invention discloses a preparation method for a multicore-single shell microsphere sustained-release system with embedded GDNF. The preparation method comprises the following steps: preparing PLGAmicrospheres with embedded GDNF; subjecting the PLGA microspheres with embedded GDNF to flushing, centrifugation and freeze-drying successively; preparing a chitosan solution from chitosan powder andan aqueous solution of glacial acetic acid, dissolving the PLGA microspheres with the embedded GDNF in water to prepare an aqueous solution of the PLGA microspheres, adding the aqueous solution of thePLGA microspheres into the chitosan solution to prepare a water phase W, mixing liquefied petrolatum with a surfactant to prepare an oil phase O, mixing the water phase W with the oil phase O to prepare a water/oil emulsion W/O, and mixing a sodium tripolyphosphate solution with the water/oil emulsion W/O so as to prepare an emulsion; and cleaning the emulsion so as to obtain the multicore-singleshell microsphere sustained-release system with the embedded GDNF. The multicore-single shell microsphere sustained-release system prepared by using the method can neutralize acidic degradation products of the PLGA microspheres and provides a good local regeneration environment to damaged nerves.

Description

technical field [0001] The invention belongs to the technical field of preparation methods of polymer composite materials, and in particular relates to a preparation method of a GDNF-embedded multi-core-single-shell microsphere slow-release system. Background technique [0002] Peripheral nerves originate from the brain and spinal cord, innervate the limbs and organs of the whole body, and serve as bridges for transmitting nerve signals between the central nervous system and corresponding functional areas, including 12 pairs of cranial nerves and 31 pairs of spinal nerves. In the peripheral nervous system (Peripheral Nervous System, PNS) of vertebrates, axons emanate from the cell bodies of neurons, which contain a large number of microfilaments and microtubules, and most axons are covered by myelin sheath mainly composed of Schwann cells (Myelinsheath) wrapping plays a certain insulating role and ensures the function of the axon to conduct electrical signals at high speed; ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61K9/52A61K47/34A61P25/00
CPCA61K9/5031A61K38/185
Inventor 曾文李维新高国栋孙杨
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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