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Method for preparing novel polyethylene glycol-poly gamma butyrolactone di-block copolymer nano drug carrying microsphere

A technology of poly-gamma butyrolactone and block copolymer, which is used in pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., to achieve adjustable sustained release performance and excellent biocompatibility , the effect of a good monodisperse state

Inactive Publication Date: 2019-11-22
QINGDAO UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, there is only one case of multi-block copolymers prepared by ring-opening polymerization of γ-butyrolactone as drug-controlled release coatings for implanted devices (US 7897168B2)

Method used

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  • Method for preparing novel polyethylene glycol-poly gamma butyrolactone di-block copolymer nano drug carrying microsphere
  • Method for preparing novel polyethylene glycol-poly gamma butyrolactone di-block copolymer nano drug carrying microsphere
  • Method for preparing novel polyethylene glycol-poly gamma butyrolactone di-block copolymer nano drug carrying microsphere

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Embodiment 1, the preparation of loading doxorubicin PEG-PBL nano microsphere

[0046]Weigh 100mg PEG-PBL (weight average molecular weight 10000, copolymerization ratio 1:1), 20mg doxorubicin, add to 4mL dichloromethane, stir at 500rpm for 10min to dissolve PEG-PBL and drug, then add 30mL deionized Water, under the pressure of 100MPa, add the primary emulsion to the micro-fluidic homogenizer, select the 75μm and 400μm flow channels for processing, and repeat the homogenization 3 times. Stir at 100rpm for 12h to volatilize the solvent, and finally centrifuge the suspension of drug-loaded microspheres at 4°C and 20,000rpm for 10min to obtain a solid that is freeze-dried to remove water and stored at 4°C.

[0047] The obtained nano drug-loaded microspheres of PEG-PBL and doxorubicin have an average particle diameter of 100 nm and a drug encapsulation rate of 85%.

Embodiment 2

[0048] Embodiment 2, preparation of paclitaxel-loaded PEG-PBL nano-microspheres

[0049] Weigh 150mg PEG-PBL (weight average molecular weight 10000, copolymerization ratio 1:1), 20mg paclitaxel, add into 4mL dichloromethane, stir at 800rpm for 10min to dissolve PEG-PBL and drug, then add 30mL deionized water to it, Under the pressure of 100MPa, the primary emulsion was added to the micro-fluidic homogenizer, and the 75 μm and 400 μm flow channels were selected for processing, and the homogenization was repeated 3 times. Stir at 100rpm for 12h to volatilize the solvent, and finally centrifuge the suspension of drug-loaded microspheres at 4°C and 20,000rpm for 10min to obtain a solid that is freeze-dried to remove water and stored at 4°C. The obtained nano drug-loaded microspheres of PEG-PBL and paclitaxel have an average particle diameter of 100 nm and a drug encapsulation rate of 90%.

Embodiment 3

[0050] Embodiment 3, preparation of paclitaxel-loaded PEG-PBL nano-microspheres

[0051] Weigh 200mg PEG-PBL (weight average molecular weight 15000, copolymerization ratio 1:2), 20mg paclitaxel, add into 4mL dichloromethane, stir at 1000rpm for 10min to dissolve PEG-PBL and drug, then add 30mL deionized water to it, Under the pressure of 40MPa, the primary emulsion was added to the micro-fluidic homogenizer, and the 75 μm and 400 μm flow channels were selected for processing, and the homogenization was repeated 3 times. Stir at 100rpm for 24h to volatilize the solvent, and finally centrifuge the suspension of drug-loaded microspheres at 4°C and 20,000rpm for 15min to obtain a solid that is freeze-dried to remove water and stored at 4°C.

[0052] The obtained nano drug-loaded microspheres of PEG-PBL and paclitaxel have an average particle diameter of 150 nm and a drug encapsulation efficiency of 80%.

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Abstract

The invention discloses a method for preparing a novel polyethylene glycol-poly gamma butyrolactone (PEG-PBL) di-block copolymer nano drug carrying microsphere. The provided PEG-PBL copolymer copolymer nano drug carrying microsphere has a small particle size, is narrowly distributed, has a high drug carrying capacity, can be slowly released for a long time, and can reduce the drug delivery frequency. In addition, according to results of biological evaluation, it is proved that the polyethylene glycol-poly gamma butyrolactone di-block copolymer nano drug carrying microsphere has excellent biocompatibility and anticancer activity. The provided novel polyethylene glycol-poly gamma butyrolactone di-block copolymer nano drug carrying microsphere has a simple preparation method, is easily produced on a large scale, and has broad application prospects in the field of drug slow release.

Description

technical field [0001] The invention belongs to the technical field of preparation of polymer drug release carriers, and in particular relates to a preparation method of a novel polyethylene glycol-polyγ-butyrolactone diblock copolymer nanometer drug-loaded microsphere. Background technique [0002] Nano-drug carriers refer to carriers with nanoscale for drug release. The use of nano-drug carriers can realize the loading of chemotherapy drugs, protein and nucleic acid drugs, etc. At present, a variety of materials are widely used in the construction of nano-drug carriers, and some of them are in the stage of commercialization or clinical research. Due to its unique structure, amphiphilic block copolymers can self-assemble into nanospheres in water, which can effectively improve the solubility of hydrophobic drugs in water. [0003] The hydrophilic block in the amphiphilic block copolymer is mainly polyoxyethylene (PEO) or polyethylene glycol (PEG), etc., and the hydrophobi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K31/704A61K31/337A61P35/00
CPCA61K9/5153A61K31/704A61K31/337A61P35/00
Inventor 李志波孙静袁帅帅沈勇
Owner QINGDAO UNIV OF SCI & TECH
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