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Use of strychnine immune nanoparticles for preparing anti-liver cancer targeted drugs

A strychnine and nanoparticle technology, which can be used in anti-tumor drugs, drug combinations, and non-active ingredients medical preparations, etc., can solve the problems of strong toxic and side effects, large drug doses, etc., achieve stable drug release, and reduce toxicity. good effect, anti-cancer effect

Inactive Publication Date: 2011-12-28
SHANGHAI UNIV OF TRADITIONAL CHINESE MEDICINE PUTUO DISTRICT CENT HOSPITAL +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, strychnine is a highly toxic traditional Chinese medicine, and its therapeutic dose is very close to the poisoning dose. The systemic drug dose is large, and its toxic and side effects are strong.

Method used

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  • Use of strychnine immune nanoparticles for preparing anti-liver cancer targeted drugs
  • Use of strychnine immune nanoparticles for preparing anti-liver cancer targeted drugs
  • Use of strychnine immune nanoparticles for preparing anti-liver cancer targeted drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Preparation method of anti-human AFP McAb-polyethylene glycol-polylactic acid block copolymer strychnine immune nanoparticle

[0042] The raw material formula is as follows:

[0043]

[0044] Among them, the polymer material (PLA-PEG-CH2-CH2-COOH) is a carboxylated polyethylene formed by copolymerization of carboxylated polyethylene glycol and polylactic acid in a weight ratio of 1:1.5~3 (preferably 1.5:2.5). Diol-polylactic acid block copolymer; its general formula is PLA-PEG-CH2-CH2-COOH, its molecular weight ranges from 40-50kD, and its structural fragments and 1 The H-NMR spectra are as figure 1 Shown.

[0045] Mix the above-mentioned oil phase and water phase, disperse with a high-shear homogenizer, shear for 5 minutes at 12000 rpm to obtain a dispersion, and then continue to emulsify the dispersion under ultrasonic conditions of 300w power, ultrasonic 5 times, each 30s, Get the first lotion. Pour the initial emulsion into the diluent of the prescription, stir while add...

Embodiment 2

[0049] In vitro drug release test of anti-human AFP McAb-polyethylene glycol-polylactic acid block copolymer strychnine immunonanoparticles

[0050] Precisely pipette 2.0ml of strychnine immune nanoparticle concentrate, place it in a dialysis bag with a molecular weight cut-off of 3,000 Daltons, tie both ends tightly, operate 3 copies in parallel, and put them into 50ml pH7.4 PBS medium In vitro release was carried out at 37°C and 100rpm rotation speed. 4ml was sampled at 0.5, 1, 2, 4, 8, 12, 16, 18, 24, 36, and 48h after the release, and 4ml was refilled. The sample was at a wavelength of 263nm Measure the UV absorption value, calculate the concentration of Bru (brimine) in the release medium and the cumulative release percentage.

[0051] Separately prepare a Bru-PBS solution with a concentration of 0.427mg / ml, accurately pipette 2.0ml of the solution, place it in a dialysis bag with a molecular weight cut-off of 3,000 Daltons, tighten the two ends, operate 3 copies in parallel, ...

Embodiment 3

[0054] Targeting determination of anti-human AFP McAb-polyethylene glycol-polylactic acid block copolymer strychnine immunonanoparticles

[0055] Incubate the anti-human AFP McAb brucine immunonanoparticles with liver cancer cell SMMC-7721 for 4 hours, wash the cells with 0.01M PBS 3 times; add FITC-labeled secondary antibody, continue to incubate for 2 hours, and wash 3 times with PBS; Observe under a confocal microscope with complementary immunofluorescence method. A 200-fold confocal microscope showed that strychnine immunonanoparticles were more evenly distributed near the liver cancer cell membrane, showing an approximate "finger ring" shape, showing good targeting, such as Figure 5 Shown (photo under confocal microscope × 200 times).

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Abstract

The invention relates to a preparation method of strychnine immune nanoparticles, and the preparation method comprises the following specific steps: step 1, dissolving carboxylated poly(ethylene glycol)-polylactic acid block copolymer and strychnine in an organic solvent, and then mixing with a polyvinyl alcohol aqueous solution to form a primary emulsion; step 2, removing the organic solvent andimpurities to obtain a strychnine nanoparticle concentrate; and step 3, sequentially adding a carbodiimide salt used as a carboxyl activation reagent and an anti-human-AFP (alpha-fetoprotein) monoclonal antibody to the strychnine nanoparticle concentrate, thus linking the carboxyl group on polyethylene glycol and the amino group of the anti-human-AFP monoclonal antibody by chemical coupling to obtain the strychnine immune nanoparticles. The preparation method provided by the invention has the advantages of simple process, high encapsulation rate, stable drug release and good drug ballability;and the obtained strychnine immune nanoparticles are used for preparing anti-tumor immune targeting drugs, and have the advantages of precise targeting drug accumulation in tumor tissue cells, stabledrug release, good anti-cancer effect, safety and the like.

Description

Technical field [0001] The present invention relates to the use of strychnine immunonanoparticles for the preparation of drugs for tumor immune targeted therapy, in particular to an anti-human AFP McAb (ie anti-human alpha-fetoprotein monoclonal antibody)-polyethylene The use of alcohol-polylactic acid block copolymer brucine immunonanoparticles for preparing anti-liver cancer specific targeted therapeutic drugs. Background technique [0002] Brucine is one of the main components of brucine, and its chemical structure is as follows: [0003] [0004] The brucine is a weakly alkaline alkaloid with poor water solubility. As a representative drug for promoting blood circulation and dredging collaterals and "attacking poison with poison", it has a promoting effect on the proliferation of T lymphocytes and has a dose-dependent functional regulation on the function of mouse lymphocytes. It has obvious anti-tumor effect and strong analgesic effect. Deng Xukun and others evaluated the eff...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K31/475A61K47/42A61K47/34A61P1/16A61P35/00
Inventor 秦建民盛霞杨林撒忠秋黄涛李琦殷佩浩张敏高科攀陈庆华马经纬沈鹤柏
Owner SHANGHAI UNIV OF TRADITIONAL CHINESE MEDICINE PUTUO DISTRICT CENT HOSPITAL
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