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Purpose of immunological nanoparticles of brucine in preparing anti-hepatoma target drugs

一种马钱子碱、纳米微粒的技术，应用在抗肿瘤药、药物组合、非有效成分的医用配制品等方向，能够解决用药剂量大、毒副作用强等问题，达到药物释放稳定、降低毒性作用、抗癌效果好的效果

Inactive Publication Date: 2012-08-22
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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  • Purpose of immunological nanoparticles of brucine in preparing anti-hepatoma target drugs
  • Purpose of immunological nanoparticles of brucine in preparing anti-hepatoma target drugs
  • Purpose of immunological nanoparticles of brucine in preparing anti-hepatoma target 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 nanoparticles

[0042] The raw material formula is as follows:

[0043]

[0044] Among them, the polymer material (PLA-PEG-CH2-CH2-COOH) is a carboxylated polyethylene glycol formed by copolymerization of carboxylated polyethylene glycol and polylactic acid at 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 range is 40-50kD, its structural fragments and 1 H-NMR measurement spectrum such as figure 1 shown.

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

Embodiment 2

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

[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 parts in parallel, and put it into 50ml of PBS medium with pH7.4 In vitro release at 37°C and 100rpm rotation speed, 4ml samples were taken at 0.5, 1, 2, 4, 8, 12, 16, 18, 24, 36, 48h after the start of the release, 4ml of rehydration solution was taken, and the samples were released at a wavelength of 263nm Determine the UV absorption value, calculate the concentration of Bru (strichnine) in the release medium and the cumulative release percentage.

[0051] Another Bru-PBS solution with a concentration of 0.427 mg / ml was prepared, 2.0 ml of the solution was precisely pipetted, placed in a dialysis bag with a molecular weight cut-off of 3,000 Daltons, ...

Embodiment 3

[0054] Determination of targeting of anti-human AFP McAb-polyethylene glycol-polylactic acid block copolymer strychnine immune nanoparticles

[0055] Anti-human AFP McAb strychnine immune nanoparticles were incubated with liver cancer cells SMMC-7721 for 4 h, and the cells were washed 3 times with 0.01M PBS; FITC-labeled secondary antibody was added, incubated for 2 h, and washed 3 times with PBS; Complementary immunofluorescence methods were observed under a confocal microscope. A 200X confocal microscope showed that strychnine immune nanoparticles were evenly distributed near the liver cancer cell membrane, showing an approximate "ring" shape, showing good targeting, as shown in Figure 5 Shown (photograph under confocal microscope × 200 times).

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Abstract

The invention relates to a purpose of immunological nanoparticles of brucine in preparing anti-hepatoma target drugs. The immunological nanoparticles of brucine are immunological target nanoparticles which treat brucine as an active component and a carboxylated polyethylene glycol-polylactic acid segmented copolymer as a drug coating accessory, and are formed by externally linking with anti-humanAFP monoclonal antibodies. The immunological nanoparticles of brucine provided by the invention, which have the characteristics of simple technology, high entrapment rate, stable drug release, and good balling, can be used for preparing antitumor target drugs which can be used for anti-hepatoma treatment. By intravenous injection, a nanometer carrier anti-human AFPMcAb-polyethylene glycol-polylactic acid segmented copolymer allows brucine aggregation in hepatoma cells to be increased, the drugs to be slowly and locally released, the effect time of the drugs to tumor cells to be prolonged, thelocal drug concentration to be improved, and the whole body toxicity of brucine to be reduced. So the immunological nanoparticles of brucine of the present invention have the advantages of accurate aggregation of target drugs in the cells of tumor tissues, stable drug release, good anticancer effect, safety and the like.

Description

technical field [0001] The present invention relates to the use of a strychnine immune nanoparticle for the preparation of drugs for tumor immune targeted therapy, in particular to an anti-human AFP McAb (i.e., anti-human alpha-fetoprotein monoclonal antibody)-polyethylene glycol The use of the alcohol-polylactic acid block copolymer strychnine immune nanoparticle in the preparation of anti-liver cancer specific targeted therapeutic drugs. Background technique [0002] Strychnine (Brucine) is one of the main components of Strychnium, and its chemical structure is as follows: [0003] [0004] The strychnine is a weakly basic alkaloid with poor water solubility. As a representative drug for promoting blood circulation and unblocking collaterals and "fighting poison with poison", it can promote the proliferation of T lymphocytes, and has a dose-dependent functional regulation of lymphocyte function in mice. It has obvious tumor inhibitory effect and strong analgesic effect...

Claims

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Application Information

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Patent Type & Authority Patents(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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