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Preparation method of zoledronic acid-loaded zeolitic imidazolate framework nanoparticle material

A technology of zoledronic acid and zeolite imidazole, which is applied in the field of preparation of zeolite imidazole framework nanoparticle materials, can solve the problems of low production efficiency, cumbersome preparation process, changes, etc., and achieves the effect of enhancing targeting ability and simplifying process

Active Publication Date: 2020-12-18
XIANGYA HOSPITAL CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The usual preparation method of ZIF-8 is completed in the methanol system, and the solubility of zoledronic acid in methanol is extremely low, and complex chemical modification of zoledronic acid is often required to be loaded into ZIF-8 nanoparticles, but this This method changes the structure of zoledronic acid and then changes its ability to inhibit osteoclasts, which limits the pharmacological activity of zoledronic acid itself, and the preparation process is cumbersome and the production efficiency is low
If ZIF-8 is prepared in the methanol system first, and then transferred to the water system to compound with zoledronic acid, ZIF-8 will form obvious agglomeration in the process of transferring to the water system, so that the zoledronic acid cannot be evenly encapsulated. load, seriously affecting the overall performance of the final nanomaterial

Method used

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Embodiment 1

[0039] A method for preparing a zoledronic acid-loaded zeolite imidazole framework nanoparticle material specifically targeting bone tissue, comprising the following steps:

[0040] (1) Prepare 9mL of 2-methylimidazole aqueous solution (pH=8.5) with a concentration of 0.04mol / L, and slowly add Zn(NO 3 ) 2 Aqueous solution (pH = 7) 1mL, continue to stir for 30min, until the reaction system is white colloid, this time is ZIF-8 nanoparticle colloid;

[0041] (2) In the zeolite imidazole framework-8 colloid obtained in step (1), add dropwise 0.6 mL of zoledronic acid aqueous solution (pH=7) with a concentration of 0.05 mol / L while stirring, and continue stirring for 30 min, 10000 g / 10 min Centrifugation and deionized water washing were repeated three times, and the obtained white precipitate was the zeolitic imidazole framework nanoparticle material (ZIF-8@ZA nanoparticles) loaded with zoledronic acid. After freeze-drying, the yield was weighed to 10 mg.

[0042] 1. Characteriza...

Embodiment 2

[0056] A method for preparing a zoledronic acid-loaded zeolite imidazole framework nanoparticle material specifically targeting bone tissue, comprising the following steps:

[0057] (1) Prepare 9mL of 2-methylimidazole aqueous solution (pH=8.5) with a concentration of 0.05mol / L, and slowly add Zn(NO 3 ) 2 Aqueous solution (pH = 7) 1mL, continue to stir for 30min, until the reaction system is white colloid, this time is ZIF-8 nanoparticle colloid;

[0058] (2) In the zeolite imidazole framework-8 colloid obtained in step (1), add dropwise 0.6 mL of zoledronic acid aqueous solution (pH=7) with a concentration of 0.05 mol / L while stirring, and continue stirring for 30 min, 10000 g / 10 min Centrifugation and deionized water washing were repeated three times, and the obtained white precipitate was the zeolite imidazole framework nanoparticle material (ZIF-8@ZA nanoparticles) loaded with zoledronic acid. After freeze-drying, the yield was 8 mg.

Embodiment 3

[0060] A method for preparing a zoledronic acid-loaded zeolite imidazole framework nanoparticle material specifically targeting bone tissue, comprising the following steps:

[0061] (1) Prepare 9mL of 2-methylimidazole aqueous solution (pH=8.5) with a concentration of 0.03mol / L, and slowly add Zn(NO 3 ) 2 Aqueous solution (pH = 7) 1mL, continue to stir for 30min, until the reaction system is white colloid, this time is ZIF-8 nanoparticle colloid;

[0062] (2) Add 0.6 mL of zoledronic acid aqueous solution (pH=7) with a concentration of 0.06 mol / L dropwise to the zeolite imidazole framework-8 colloid obtained in step (1), and continue stirring for 30 min, 10000 g / 10 min Centrifugation and deionized water washing were repeated three times, and the obtained white precipitate was the zeolite imidazole framework nanoparticle material (ZIF-8@ZA nanoparticles) loaded with zoledronic acid. After freeze-drying, the yield was 8 mg.

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Abstract

The invention discloses a preparation method of a zoledronic acid-loaded zeolitic imidazolate framework nanoparticle material. The preparation method comprises the following steps: preparing a 2-methylimidazole aqueous solution, dropwisely adding a Zn(NO3)2 aqueous solution while stirring, continuing stirring until the reaction system becomes white colloid, dropwisely adding a zoledronic acid aqueous solution into the obtained zeolitic imidazolate framework-8 colloid while stirring, continuously stirring, centrifuging and washing to obtain white precipitate, namely the zoledronic acid-loaded zeolitic imidazolate framework nanoparticle material. The present invention adopts a one-step method to synthesize the zoledronic acid-loaded zeolitic imidazolate framework nanoparticle material (ZIF-8@ZA) in a water system, can load zoledronic acid into ZIF-8 nanoparticles without modifying zoledronic acid, not only preserves pharmacological activity of zoledronic acid itself, but also simplifiesthe process, has simple operation and high production efficiency.

Description

technical field [0001] The invention belongs to the technical field of targeting materials, and in particular relates to a preparation method of a zoledronic acid-loaded zeolite imidazole framework nanoparticle material specifically targeting bone tissue. Background technique [0002] The particularity of the anatomical structure of human bone tissue leads to poor blood circulation in some parts (such as subchondral bone, skull, etc.). Intravenous administration is often difficult to form an effective blood concentration in the lesion; although local injection can overcome this obstacle to a certain extent, the hard bone tissue makes local injection impossible most of the time, and repeated local injection will not only aggravate the The pain of the patient increases the risk of infection significantly. Therefore, how to increase the blood concentration of therapeutic drugs in the bone tissue of the lesion and improve the therapeutic effect is an important scientific proble...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/22A61K47/02A61K31/675A61P19/10A61P35/04A61P19/08
CPCA61K9/5123A61K9/5115A61K31/675A61P19/10A61P35/04A61P19/08
Inventor 胡懿郃潘依潇汪龙
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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