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Preparation method of chitosan-based polymer point-loaded drug microspheres

A technology of polymer dots and drug-loaded microspheres, which is applied in the field of medicine and pharmacy, can solve the toxicity of semiconductor quantum dots and other problems, and achieve the effects of good slow release and traceability, mild reaction conditions, and uniform particle size distribution

Active Publication Date: 2018-11-02
金湖县综合检验检测中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] If amphiphilic chitosan is endowed with its fluorescent properties as a drug carrier, it can also be used as a drug carrier. At present, there are two main methods: grafting amphiphilic chitosan with fluorescent organic small molecules, or encapsulating semiconductor quantum dots to achieve The effect of fluorescent tracer, but the grafted small molecule fluorescent molecules and semiconductor quantum dots have potential toxicity

Method used

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  • Preparation method of chitosan-based polymer point-loaded drug microspheres
  • Preparation method of chitosan-based polymer point-loaded drug microspheres
  • Preparation method of chitosan-based polymer point-loaded drug microspheres

Examples

Experimental program
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Effect test

Embodiment 1

[0030] 1) Synthesis of N-citrated chitosan-g-polyethylene glycol monomethyl ether CS-g-mPEG-CA

[0031] Dissolve 5.0g of citric acid in 100ml of deionized water, add 1.0g of chitosan-g-polyethylene glycol monomethyl ether CS-g-mPEG to it, stir for 12 hours, then add 0.02mol of EDC and 0.02mol of NHS, keep stirring and keep away from light for 48 hours, and the reacted product is dialyzed with deionized water for 3 days (the molecular weight cut-off of the selected dialysis bag is 8000-14000) and then freeze-dried.

[0032] (2) Synthesis of N-citrated chitosan-g-polyethylene glycol monomethyl ether polymer dots P(CS-g-mPEG-CA)Ds

[0033] Take 0.5g of the different kinds of CS-g-mPEG-CA prepared above in an autoclave, add 0.5g of anhydrous citric acid and 2ml of N-(2 hydroxyethyl)ethylenediamine, mix them evenly and disperse them in In a mixed solution of 4ml polyethylene glycol 400 and 16ml deionized water, react at 180°C for 6 hours, dialyze the reaction product through deion...

Embodiment 2

[0037] 1) Synthesis of N-citrated chitosan-g-polyethylene glycol monomethyl ether CS-g-mPEG-CA

[0038] Dissolve 5.0g of citric acid in 100ml of deionized water, add 1.0g of chitosan-g-polyethylene glycol monomethyl ether CS-g-mPEG to it, stir for 12 hours, then add 0.02mol of EDC and 0.02mol of NHS, keep stirring for 48 hours in the dark, and dialyze the reaction product with deionized water for 3 days (the molecular weight cut-off of the selected dialysis bag is 8000-14000) and freeze-dry to obtain CS-g-mPEG-CA.

[0039] (2) Synthesis of N-citrated chitosan-g-polyethylene glycol monomethyl ether polymer dots P(CS-g-mPEG-CA)Ds

[0040] Take 0.5g of N-citrated chitosan-g-polyethylene glycol monomethyl ether CS-g-mPEG-CA prepared above, 0.5g of anhydrous citric acid and 2ml of N-(2 hydroxyethyl)ethylenediamine In a high-pressure reactor, after mixing evenly, it was dispersed in a mixed solution of 4ml polyethylene glycol 400 and 16ml deionized water, reacted at 180°C for 3 hou...

Embodiment 3

[0045] 1) Synthesis of N-citrated chitosan-g-polyethylene glycol monomethyl ether CS-g-mPEG-CA

[0046] Dissolve 4.0g of citric acid in 100ml of deionized water, add 1.0g of chitosan-g-polyethylene glycol monomethyl ether CS-g-mPEG to it, stir for 8 hours, then add 0.05mol of EDC and 0.05mol of NHS, keep stirring for 48 hours in the dark, and dialyze the reacted product with deionized water for 3 days (the molecular weight cut-off of the selected dialysis bag is 8000-14000) and vacuum-dry to obtain CS-g-mPEG-CA.

[0047] (2) Synthesis of N-citrated chitosan-g-polyethylene glycol monomethyl ether polymer dots P(CS-g-mPEG-CA)Ds

[0048] Take 0.5g of CS-g-mPEG-CA prepared above, 0.5g of anhydrous citric acid and 1.5ml of N-(2 hydroxyethyl) ethylenediamine in an autoclave, mix well and disperse in 5ml of polyethylene glycol In a mixed solution of 400 and 14ml deionized water, react at 200°C for 3 hours, dialyze the reacted product with deionized water for 3 days (the molecular we...

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Abstract

The invention discloses a preparation method of chitosan-based derivative polymer point drug carrying microspheres. The preparation method comprises the following steps of: taking N-citric chitosan-g-methoxypolyethylene glycols, anhydrous citric acid and N-2-hydroxy ethylenediamine, uniformly dispersing N-citric chitosan-g-methoxypolyethylene glycols, anhydrous citric acid and N-2-hydroxy ethylenediamine into a mixed solution of polyethylene glycol 400 and deionized water, performing reaction, dialyzing reaction products with water, and then drying, thereby obtaining N-citric chitosan-g-methoxypolyethylene glycol polymer points; and dispersing doxorubicin into dichloromethane, dissolving the prepared polymer points into an acetate solution, dropwise adding a polymer point solution into dichloromethane dispersion liquid of doxorubicin, dropwise adding ammonia water to regulate pH until the solution is neutral, performing ultrasonic treatment, standing for liquid separation, and removing a water phase centrifuging, and drying obtained precipitates. The prepared drug carrying microspheres have relatively good fluorescence characteristic, are non-toxic, are uniform in particle size distribution, can be used for wrapping medicaments, and have favorable tracing and slow-release effects.

Description

technical field [0001] The invention belongs to the field of medicine and pharmacy, and more specifically relates to a preparation method of chitosan-based derivative polymer point-loaded drug microspheres. Background technique [0002] Cancer is a disease that seriously threatens human health and life. Chemotherapy, surgery, and radiotherapy are the three main means of cancer treatment. However, traditional anticancer drugs have poor water solubility, low bioavailability, and low treatment efficiency. Encapsulation can greatly improve the hydrophilicity of drugs, improve their availability, and prolong blood circulation time, so nano drug-loading systems have become a research hotspot in recent years. [0003] Chitosan is the only natural cationic amino polysaccharide, which has good biocompatibility, biodegradability, and low toxicity. The hydroxyl and amino groups on its repeated sugar units have active chemical properties, and chitosan can be chemically modified. prope...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/50A61K47/36A61K49/00A61K31/704A61P35/00
CPCA61K9/5036A61K31/704A61K49/0054A61K49/0091
Inventor 于淑娟陈宽汪丰陆树文
Owner 金湖县综合检验检测中心