Preparation method and application of pH sensitive drug delivery system with carbon nanomaterial as carrier

A carbon nanomaterial and delivery system technology, which is applied in the field of preparation of pH-sensitive drug delivery systems, can solve the problems that tumor cell proliferation cannot be well inhibited, and side effects are large.

Inactive Publication Date: 2013-07-10
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In view of the above situation, in order to solve the defects of the prior art, the purpose of the present invention is to provide a preparation method and application of a pH-sensitive drug

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] 1) Amination modification of fullerene according to the method described in "A Water-Soluble Fullerene and Its Application" with patent application number 201210406707.3;

[0050] 2) Add 50 mg of the above amino-containing fullerene, 40 mg of p-carboxyphenylhydrazine (HBA) and 100 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl) and Mix 60mg of N-hydroxysuccinimide (NHS) in 20ml of phosphate buffered saline (PBS), mix well at room temperature, stir at 400r / min for 24h to fully react, add 50-100mL of absolute ethanol or acetone, and let stand 2h, and then filtered through a 0.22μm polyvinylidene fluoride microporous membrane, repeating the operation 5-10 times, and vacuum drying at 20-60°C for 24-56h to obtain p-carboxyphenylhydrazine derivatives of fullerenes;

[0051]3) Mix 20 mg of p-carboxyphenylhydrazine derivative of fullerene obtained above and 40 mg of carbonyl-containing antineoplastic drug in 20 mL of dimethyl sulfoxide (DMSO), and...

Embodiment 2

[0053] 1) Add 110-120 mg of carbon nanotubes into 40 mL of a mixed acid solution consisting of sulfuric acid with a mass concentration of 98% and nitric acid with a mass concentration of 65-68% at a volume ratio of 3:1, and then add 10-15 ml of a mass concentration of 30 % hydrogen peroxide solution, ultrasonicated for 1 hour in an ultrasonic cleaner with a power of 300-400W, diluted with ultrapure water, filtered using a 0.45 μm microporous membrane and a Buchner funnel, and continuously rinsed with ultrapure water to pH =7, put it into an oven and dry at a constant temperature of 80°C to obtain carboxylated carbon nanotubes;

[0054] 2) Add 45-50 mg of the above-mentioned carboxylated carbon nanotubes to 20 mL of ammoniating reagent, then add 1 g of N,N'-dicyclohexylcarbodiimide, ultrasonically disperse it for 10 min, put it in an oil bath, and heat it at 120 ° C , stirred at 100 r / min, condensed and refluxed for 48 hours, after the reaction, the reactant was cooled to room ...

Embodiment 3

[0058] 1) Add 50 mg of graphene oxide into 120 mL of a mixed acid solution consisting of sulfuric acid with a mass concentration of 98% and nitric acid with a mass concentration of 65-68% at a volume ratio of 3:1, and then add 4-12 mL of 30% Hydrogen peroxide solution was ultrasonicated for 1 hour in an ultrasonic cleaner with an ultrasonic power of 300-400W, diluted with ultrapure water, filtered using a 0.45 μm microporous membrane and a Buchner funnel, and continuously rinsed with ultrapure water until the pH was Until it is neutral, put it in an oven and dry it at a constant temperature of 80°C to obtain carboxylated graphene oxide;

[0059] 2) Add 50 mg of the above-mentioned carboxylated graphene oxide to 20 mL of ammoniating reagent, then add 1 g of N,N'-dicyclohexylcarbodiimide, ultrasonically disperse it for 10 min, put it in an oil bath, and heat it at 120 °C and 100 r Stir at 1 / min, condense and reflux for 48 hours. After the reaction, cool the reactant to room temp...

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Abstract

The invention relates to a preparation method and application of a pH sensitive drug delivery system with a carbon nanomaterial as a carrier. The pH sensitive drug delivery system can be used for effectively solving the problems that the traditional tumor therapy drugs are high in side effect and incapable of well inhibiting the tumor cell proliferation. The technical scheme for solving the problems is as follows: the preparation method comprises the following steps of: modifying the original carbon nanomaterial, and then, subjecting the modified original carbon nanomaterial and an ammoniation reagent to a reaction; after connecting an amino with reaction activity to the surface of the carbon nanomaterial, subjecting the carbon nanomaterial and p-hydrazinobenzoic acid to a reaction to generate a p-hydrazinobenzoic acid derivative of the carbon nanomaterial; and then, subjecting the p-hydrazinobenzoic acid derivative and a carbonyl contained anti-tumor drug to a reaction to obtain the pH sensitive drug delivery system with the carbon nanomaterial as the carrier, wherein the carbon nanomaterial is one selected from fullerene, a carbon nanotube and graphene oxide. The pH sensitive drug delivery system is good in biocompatibility, large in specific surface area and high in chemical inertness, has a control release feature and a targeting property, and is an innovation of the anti-tumor drug.

Description

technical field [0001] The invention relates to medicine, in particular to a preparation method and application of a pH-sensitive drug delivery system with carbon nanomaterials as carriers. Background technique [0002] In recent years, carbon nanomaterials have been widely used as drug carriers. Among nanomaterials, carbon nanomaterials including fullerenes, carbon nanotubes and graphene oxide have been one of the frontier fields of international science in recent years. Carbon nanotubes (CNTs) have attracted extensive attention from various disciplines due to their unique electrical, mechanical, optical, and thermodynamic properties. Huge specific surface area (~2600m 2 / g), ultra-high mechanical strength, low density, outstanding chemical and thermal stability and electron-rich characteristics, unique transmembrane ability, and large delocalized π bonds, which can form a relatively good relationship with many biomedical molecules. The strong π-π bond interaction makes...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K41/00A61K45/00A61P35/00
Inventor 史进进刘艳王蕾高君张振中余晓媛张静马柔柔刘瑞瑗马丹
Owner ZHENGZHOU UNIV
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