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Targeted chitosan cross-linked gel as well as preparation method and application thereof

A technology of chitosan cross-linking and chitosan, which is applied in the direction of pharmaceutical formulations, non-active ingredient medical preparations, medical preparations containing active ingredients, etc., to achieve safe and efficient drug delivery, enhanced circulatory stability, and good pH The effect of buffer capacity

Active Publication Date: 2020-12-01
DALIAN NATIONALITIES UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is to overcome the defects of existing chitosan drug carriers, to provide materials containing imidazole cross-linked chitosan and hyaluronic acid targeting structure and its preparation method

Method used

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  • Targeted chitosan cross-linked gel as well as preparation method and application thereof
  • Targeted chitosan cross-linked gel as well as preparation method and application thereof
  • Targeted chitosan cross-linked gel as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Put 0.5g of dimethyl imidazole-4,5-dicarboxylate into a 100mL three-neck round bottom flask, add 10mL of methanol, and heat to reflux at 70°C until the dimethyl imidazole-4,5-dicarboxylate is completely dissolved Afterwards, 2 mL of 80% hydrazine hydrate was added and refluxed for 3 h, washed with methanol, centrifuged twice, and the obtained sample was vacuum-dried to obtain the product imidazole-4,5-dicarboxylic acid dimethylhydrazide.

[0037] Imidazole-4,5-dicarboxylic acid dicarboxylic acid hydrazide 1 HNMR spectrum as figure 1 As shown, in the figure, a: imidazole-4,5-dicarboxylic acid dimethyl ester b: imidazole-4,5-dicarboxylic acid dimethylhydrazide.

Embodiment 2

[0039] Weigh 1.7760 g of chitosan (MW=5KDa), place it in a 250 mL three-necked round bottom flask, dissolve it in 50 mL of NaAc / HAc buffer solution with pH=4.5, and ultrasonicate for 30 min to dissolve it. Weigh 0.2246g of sodium periodate, dissolve it in 20mL of NaAc / HAc buffer solution with pH=4.5, place the two solutions in an ice bath, fill with nitrogen gas, degas for 20 minutes, mix them, and stir them in an ice bath for 24 hours Afterwards, 10 mL of ethylene glycol was added to terminate the reaction. The product solution is taken out, poured into a petri dish, put into a refrigerator to freeze, and the solidified sample is taken out and placed in a freeze dryer to freeze-dry to obtain the product formyl chitosan.

Embodiment 3

[0041] Weigh 0.05g of formyl chitosan (MW=5KDa) prepared in Example 2 in a single-necked flask and add 20mL of deionized water to dissolve, dissolve 0.0055g of imidazole-4 prepared in Example 1 with 10mL of dimethyl sulfoxide, 5-dicarboxylic acid dimethyl hydrazide, add imidazole-4,5-dicarboxylic acid dimethyl hydrazide solution dropwise to the single-necked flask containing formyl chitosan solution, heat and reflux at 70°C for 6h, after the reaction is completed The product solution was taken out, and after two days of dialysis with deionized water, the dialysate was frozen and freeze-dried to obtain the product imidazole cross-linked chitosan gel (CFCS). Under ultrasonic conditions, 1% hyaluronic acid aqueous solution with a volume ratio of 1:1 was added dropwise, and the ultrasonic was continued, and the resulting solution was dialyzed and freeze-dried to obtain targeted chitosan cross-linked gel (HCFCS).

[0042] The FTIR spectra of hyaluronic acid (HA), imidazole cross-li...

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Abstract

The invention provides chitosan cross-linked gel as well as a preparation method and application thereof. According to the method, chitosan and imidazole-4,5-dicarboxylic acid dimethyl ester are usedfor preparing imidazole cross-linked chitosan, hyaluronic acid is adopted for coating, and the gel has high proton buffer capacity and a drug entrapment function, has CD44 targeting property, can be used for drug auxiliary materials and has wide application prospects.

Description

technical field [0001] The invention relates to a targeting chitosan cross-linked gel material, in particular to a surface-coated hyaluronic acid and imidazole cross-linked chitosan material and its preparation method and application, belonging to the technical field of biomedicine. Background technique [0002] Nanogels have the advantages of high stability, good biocompatibility, and large drug loading capacity, which can prevent drug degradation and clearance from the circulatory system. Loading various molecules such as deoxyribonucleic acid, ribonucleic acid, protein, and inorganic materials in the nanogel structure helps to improve the residence time of drugs in the systemic circulation and their biocompatibility, so nanogels can be used as a new type of delivery carrier. [0003] Chitosan (CS) is a deacetylated chitin derivative composed of β-1,4-linked glucosamine and a small amount of N-acetylglucosamine, which has reactive functional groups, biocompatibility, biod...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K47/36A61K47/54A61K45/00
CPCA61K9/06A61K47/36A61K47/545A61K45/00
Inventor 张树彪陈会英范雪枫蓝浩铭支德福
Owner DALIAN NATIONALITIES UNIVERSITY
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