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Preparation and application method of pharmaceutical albumin nanoparticle

A technology of albumin nanoparticles and albumin, which is applied in the fields of pharmaceutical preparations and tumor treatment to achieve good anti-tumor effect

Inactive Publication Date: 2016-08-03
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, clinical studies have found that when monoclonal antibodies and paclitaxel albumin nanoparticles are used in combination, the effect is similar to that of monoclonal antibodies and paclitaxel. 联合用药没有显著差异(RugoHSetal.RandomizedphaseIIItrialofpaclitaxelonceperweekcomparedwithnanoparticlealbumin-boundnab-paclitaxelonceperweekorixabepilonewithbevacizumabasfirst-linechemotherapyforlocallyrecurrentormetastaticbreastcancer:CALGB40502 / NCCTGN063H(Alliance)[J].JournalofClinicalOncology,2015,33(21):2361-2369.)

Method used

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  • Preparation and application method of pharmaceutical albumin nanoparticle
  • Preparation and application method of pharmaceutical albumin nanoparticle
  • Preparation and application method of pharmaceutical albumin nanoparticle

Examples

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Effect test

example 1

[0064] Example 1, the preparation of drug albumin nano

[0065] (1) Preparation of Paclitaxel Avidin Albumin Nanoparticles

[0066]Avidin and human serum albumin were dissolved in water to form a mixed aqueous solution, wherein the concentration of albumin was 1% (W / V), and the weight ratio of albumin to avidin was 20:1. Paclitaxel accounting for 10% (W / W) of the total protein weight was dissolved in 3.5% (V / V) organic solvent (chloroform:ethanol=9:2). Probe ultrasound for 1-3min to prepare colostrum. The ultrasonic condition of the probe is 40W power, working for 2s and resting for 2s. Homogenize the mixed solution under the pressure of 10000-20000psi, and circulate 5-10 times. Subsequently, the probe was ultrasonicated for 5-10 min, and the ultrasonic condition of the probe was 40W power, working for 2s, and resting for 2s. Rotary evaporation at 40°C for 15-40min, after removing the organic solvent, filtered the avidin albumin nanoparticles with a 0.22μm filter membrane....

example 2

[0079] Human serum albumin was labeled with rhodamine N-hydroxysuccinimide ester under neutral conditions. Rhodamine-labeled human serum albumin was used to prepare paclitaxel-avidin albumin nanoparticles as described above. A549 cells were inoculated in confocal small dishes and incubated for 24 hours. After the cells adhered to the wall, the original culture medium was discarded. For the pre-targeting antibody group, biotinylated cetuximab (2 μg / ml) was pre-incubated for 1 h, discarded, and washed twice with PBS. Paclitaxel-avidin albumin nanoparticles were diluted with serum-free culture medium to a rhodamine concentration of 1 μg / ml, and added to the confocal small dish pretargeted with biotinylated monoclonal antibody and the confocal small dish not pretargeted respectively. Half an hour later, the interaction between paclitaxel avidin albumin nanoparticles and A549 cells was observed with or without biotinylated monoclonal antibody pre-targeted A549 cells by laser confo...

example 3

[0080] Example 3. Biotinylated monoclonal antibody improves the evaluation of the distribution of paclitaxel avidin albumin nanoparticles in tumor sites

[0081] According to the preparation method of pharmaceutical albumin nanoparticles provided by the present invention, paclitaxel avidin albumin nanoparticles containing paclitaxel, avidin and albumin are prepared. At the same time, paclitaxel albumin nanoparticles without avidin are prepared according to the preparation method of pharmaceutical albumin nanoparticles provided by the present invention.

[0082] Inject A549 tumor cells into the armpit of nude mice to establish a nude mouse model bearing A549 tumor until the tumor volume reaches 500mm 3 At that time, they were randomly divided into two groups, namely the non-pretargeted group and the biotinylated monoclonal antibody pretargeted group. In the non-pretargeting group, 0.2 ml of Paclitaxel Avidin Albumin Nanoparticles containing DiR (2ug / ml) was injected into the t...

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Abstract

The invention belongs to the field of pharmaceutical preparations, and provides a pharmaceutical albumin nanoparticle, a preparation method and application of the nanoparticle to tumor targeting therapy. The nanoparticle is made from two types of proteins, namely avidin and albumin, encapsulating slightly-soluble antitumor drugs. The electrostatic interaction exists between avidin and albumin, and avidin in the nanoparticle can be combined with biotin. Avidin can target the nanoparticle encapsulating the drugs on a biotin enrichment part. Before the application of the nanoparticle, a biotinylated antibody is used for pre-targeting on a tumor part, and can improve the distribution of a nanoparticle preparation in the tumor part. The biotinylated antibody and the nanoparticle preparation are combined for therapy, thereby playing better antitumor effect than the effect played by the combination of a monoclonal antibody and an albumin nanoparticle without avidin.

Description

technical field [0001] The invention relates to a pharmaceutical albumin nanoparticle composed of avidin, albumin and a hydrophobic antitumor drug, a preparation method thereof and an application in tumor targeting therapy, belonging to the field of pharmaceutical preparations and tumor treatment. Background technique [0002] Tumor is a serious disease that threatens human health. Traditional antineoplastic drugs (such as paclitaxel, docetaxel and doxorubicin, etc.) have strong toxic and side effects. In order to enhance the effectiveness of drugs and reduce side effects, targeted therapy for tumors has emerged as the times require. [0003] The anti-tumor treatment of monoclonal antibodies has a history of 18 years, and it is now successfully used in the treatment of leukemia and tumors clinically. Monoclonal antibodies can directly act on tumor cell receptors, block signaling pathways, and inhibit tumor growth; they can also mediate the patient's own immune system to ki...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K45/06A61K31/337A61K31/4745A61K31/12A61K39/395A61K38/08A61K38/12A61K9/14A61P35/00
CPCA61K9/146A61K31/12A61K31/337A61K31/4745A61K38/08A61K38/12A61K39/395A61K45/06A61K2300/00
Inventor 张强刘同舟代文兵何冰王学清张华陈斌龙
Owner PEKING UNIV
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