A core-shell structured chitosan-based nano-prodrug that co-loads doxorubicin and platinum drugs and its preparation method and application
A technology of platinum-based drugs and core-shell structure, which is applied in the direction of drug combinations, pharmaceutical formulas, and medical preparations of non-active ingredients. Clear, simple effect of drug loading
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[0043]A preparation method of a core-shell structured chitosan-based nano-prodrug co-loaded with doxorubicin and platinum drugs of the present invention is as follows: firstly, 3,3'-dithiodipropionyl Hydrazine is bonded to chitosan derivatives to obtain hydrazide chitosan derivatives. At the same time, doxorubicin is linked to 3,3'-dithiodipropionyl hydrazide through a hydrazone bond to obtain hydrazide doxorubicin Then the aqueous solution of hydrazidated chitosan derivatives, hydrazidated doxorubicin and platinum drugs is mixed evenly, and the core-shell structure type chitosan-based nano-prodrug is obtained through the self-assembly process, which specifically includes the following steps:
[0044] (1) Preparation of hydrazidated chitosan derivatives: Aldehydated furan solution is added dropwise to water-soluble chitosan solution, aldehyde groups and amino groups undergo a Schiff base reaction, and are reduced by sodium cyanoborohydride to form Furanated chitosan derivative...
Embodiment 1
[0066] (1) Preparation of hydrazidated hydroxyethyl chitosan: 3-(2-furyl) acrolein solution with a mass concentration of 0.33% was added dropwise to 1.0% hydroxyethyl chitosan (MW = 170kDa) solution and mix well, the molar ratio of 3-(2-furyl) acrolein to amino group in hydroxyethyl chitosan is 10:8, at 30℃ and N 2 React under the atmosphere for 12h, then add the sodium cyanoborohydride solution with a mass concentration of 0.6%. The amount of sodium cyanoborohydride is 1.3 times the number of Schiff base bonds. 2 The reduction reaction was continued for 12 hours under the atmosphere to form a furanated hydroxyethyl chitosan crude product, which was dialyzed in deionized water for 72 hours with a dialysis bag with a molecular weight cut-off of 3500 Da and then freeze-dried to obtain furanated hydroxyethyl chitosan;
[0067] Be that the mass concentration of 1.0% maleimide caproic acid solution is 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide solution and 0.57mmol mass concent...
Embodiment 2
[0079] (1) Preparation of hydrazidated hydroxyethyl chitosan: 3-(2-furyl) acrolein solution with a mass concentration of 0.33% was added dropwise to 1.0% hydroxyethyl chitosan (MW = 200kDa) solution and mix well, the molar ratio of 3-(2-furyl) acrolein to amino group in hydroxyethyl chitosan is 10:1, at 30 ℃ and N 2 React under the atmosphere for 12h, then add a sodium cyanoborohydride solution with a mass concentration of 0.6%, the amount of sodium cyanoborohydride is 1.1 times the number of Schiff base bonds, at 20 ° C and N 2 The reduction reaction was continued for 1 h under the atmosphere to form a furanated hydroxyethyl chitosan crude product, which was dialyzed in deionized water for 72 h with a dialysis bag with a molecular weight cut-off of 3500 Da and then freeze-dried to obtain furanated hydroxyethyl chitosan;
[0080] Be that the mass concentration of 1.0% maleimide caproic acid solution is 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide solution and 0.57mmol mass c...
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