Folic acid modified chitosan micro-capsule with reducing responsiveness and preparation method thereof

A technology of chitosan microcapsules and responsiveness, which is applied in the field of reduction-responsive microcapsules and preparation, which can solve the problems of chitosan microcapsules and achieve controllable release, simple operation, and high drug loading capacity. big effect

Active Publication Date: 2016-02-17
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The preparation of folic acid-modified microcapsules has been reported in recent years, and has potential applications in the fields of drug targeting technology, but there is no report on the preparation of reduction-responsive folic acid-modified chitosan microcapsules by ultrasonic method

Method used

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Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0031] A preparation method of folic acid-modified chitosan with reduction-responsive microcapsules includes the following steps:

[0032] a. Dissolve chitosan in a buffer solution of acetic acid and sodium acetate at pH=5.0 to prepare a certain concentration of chitosan aqueous solution;

[0033] b. Combine compounds or biomolecules containing sulfhydryl groups with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in a molar ratio of 1:1:1 Dissolve, prepare an aqueous solution with a concentration of 0.1-1.0 mg / ml, and activate for 20 minutes;

[0034] c. Mix the above two solutions at a volume ratio of 5:1 to 1:5 under the protection of nitrogen, stir and react for 12 hours, and repeatedly centrifuge and wash to remove unreacted sulfhydryl-containing compounds or biomolecules to obtain sulfhydryl-modified chitosan Aqueous solution

[0035] d. Dissolve folic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide...

Embodiment 1

[0045] Dissolve chitosan in a buffer solution of acetic acid and sodium acetate at pH=5.0 to prepare a 0.1mg / ml chitosan aqueous solution; mix cysteine ​​hydrochloride and 1-(3-dimethylaminopropyl)-3 -Ethylcarbodiimide hydrochloride and N-hydroxysuccinimide are dissolved in a molar ratio of 1:1:1, and an aqueous solution with a concentration of 0.1mg / ml is prepared, and activated for 20 minutes; under the protection of nitrogen, the volume ratio is 1 :1 Mix the above two solutions, stir and react for 12 hours, repeat centrifugal washing to remove unreacted cysteine ​​hydrochloride, and obtain an aqueous solution of chitosan containing sulfhydryl modification; combine folic acid and 1-(3-dimethylaminopropyl) )-3-Ethylcarbodiimide hydrochloride and N-hydroxysuccinimide are dissolved in a molar ratio of 1:2:2, and an aqueous solution with a concentration of 0.1 / ml is prepared, and activated for 1h in the dark; Mix the chitosan aqueous solution with pH=5.0 and the folic acid activa...

Embodiment 2

[0047] Dissolve chitosan in a buffer solution of acetic acid and sodium acetate at pH=5.0 to prepare a 0.5mg / ml chitosan aqueous solution; add mercaptoundecanoic acid [HS-(CH 2 ) n -COOH, the number of alkyl groups n=10] and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide are dissolved in a molar ratio of 1:1:1 , Prepare an aqueous solution with a concentration of 0.1 mg / ml, activate for 20 min; mix the above two solutions at a volume ratio of 1:5 under the protection of nitrogen, stir and react for 12 hours, repeat centrifugal washing to remove unreacted mercaptoundecanoic acid, and obtain Sulfhydryl modified chitosan aqueous solution; folic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and N-hydroxysuccinimide in a molar ratio of 1:2:2 Dissolve and prepare an aqueous solution with a concentration of 1.0 mg / ml, and activate it for 1 hour in the dark; mix the chitosan aqueous solution with pH=5.0 and the folic acid activa...

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Abstract

The invention relates to a folic acid modified chitosan micro-capsule with reducing responsiveness and a preparation method thereof. The capsule wall is modified by folic acid and provided with a disulfide bond structure with reducing responsiveness, a chitosan crosslinking film modified by folic acid and compounds with sulfydryl or biomolecules is adopted as the capsule wall, and the oil phase loaded with hydrophobic drugs is adopted as a core material. Firstly, chitosan is modified by folic acid and the compounds with sulfydryl or the biomolecules, ultrasonic radiation is conducted on the oil phase loaded with the hydrophobic drugs and a chitosan water solution modified by the compounds with sulfydryl or the biomolecules, and the chitosan drug-loaded micro-capsule with the capsule wall provided with folic acid and the disulfide bond structure is obtained. The preparation method is rapid, easy and convenient, efficient, environmentally friendly and wide in material source, the product is pure and free of toxins, the drug loading capacity is large, the micro-capsule can be widely applied to covering the hydrophobic drugs, targeted conveyance of drugs is achieved through the targeting of folic acid, controllable release of the drugs is achieved through the reducing responsiveness of disulfide bonds, and good application prospects are achieved.

Description

Technical field [0001] The invention relates to a biomedical material, in particular to a folic acid-modified microcapsule with reduction responsiveness and a preparation method. Background technique [0002] Microcapsules are micro-containers or packages with a specific geometric structure composed of encapsulated substances. Due to the particularity of their structure, the variability of performance and the wide range of applications, they are used in the fields of agriculture, food and biomedicine. Significant application. There are many kinds of materials for preparing microcapsules, mainly natural polymer materials (proteins, lipids, etc.) or synthetic polymer materials (PMMA, polylactic acid, etc.), or inorganic compounds (SiO 2 , CaCO 3 Wait). Among them, natural polymer materials have important application value in the preparation of microcapsules due to their good biocompatibility, non-toxicity and easy degradability. There are many methods for preparing microcapsules....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K47/22A61K47/44A61K31/337A61K31/17A61K31/4745A61K31/357A61K31/704
CPCA61K9/5036A61K31/17A61K31/337A61K31/357A61K31/4745A61K31/704A61K47/22A61K47/44
Inventor 崔学军关新禹王洪艳
Owner JILIN UNIV
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