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Preparation method of polyene-containing taxol nanoparticle mixed micelle preparation and freeze-drying agent

A technology of docetaxel and mixed micelles is applied in the field of preparation of nanoparticle mixed micelle preparations and freeze-dried agents, and can solve the problems of inconvenient clinical medication, difficulty in guaranteeing the treatment level, and complicated use methods.

Inactive Publication Date: 2012-05-09
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The preparation needs to be diluted with a special injection solvent before use, and the requirements for operators are extremely strict and the use method is cumbersome; the preparation contains a large amount of Tween, which can easily cause adverse reactions such as hemolysis and allergies, and it is necessary to take dexamethasone and other drugs in advance Prevention and treatment, clinical medication is inconvenient, medication safety is low
[0007] In recent years, researchers have gradually realized that it is difficult to guarantee the improvement of the treatment level by simply relying on the discovery of new medicinal compounds.

Method used

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  • Preparation method of polyene-containing taxol nanoparticle mixed micelle preparation and freeze-drying agent
  • Preparation method of polyene-containing taxol nanoparticle mixed micelle preparation and freeze-drying agent
  • Preparation method of polyene-containing taxol nanoparticle mixed micelle preparation and freeze-drying agent

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Experimental program
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Effect test

Embodiment 1

[0037] Weigh 20mg of PLA(30000)-PEG(3000) copolymer, 2mg of docetaxel, add 2ml of dichloromethane, ultrasonically dissolve the carrier material and drug, use a 2.5ml syringe to absorb the solution, and use a micro-syringe pump to add the solution dropwise (The drop rate is 12ml / h) in 20ml of ethanol, the magnetic stirring speed is 300r / min, after stirring for 10min, add 20ml of distilled water, volatilize overnight, volatilize until the solution is 2ml, and store in a sealed container at 4°C.

[0038] Results: The average particle size of the prepared PLA-PEG nanoparticles or micelles or nanoparticles mixed micelles was 193±5.4nm.

Embodiment 2

[0040] Weigh 30mg of PLA(30000)-PEG(3000) copolymer, 2mg of docetaxel, add 2ml of dichloromethane, ultrasonically dissolve the carrier material and drug, use a 2.5ml syringe to draw the solution, and use a micro-injection pump to drip the solution Add (dropping rate is 12ml / h) 20ml ethanol, magnetic stirring speed is 400r / min, after stirring for 10min, add 20ml distilled water, volatilize overnight, volatilize until the solution is 2ml, seal and store at 4°C.

[0041] Results: The average particle size of PLA-PEG nanoparticles or micelles or nanoparticle mixed micelles was 156±3.4nm.

Embodiment 3

[0043] Weigh 40mg of PLA(12000)-PEG(2000) copolymer, 2mg of docetaxel, add 2ml of dichloromethane, ultrasonically dissolve the carrier material and drug fully, use a 2.5ml syringe to draw the solution, and use a micro-syringe pump to drip the solution Add (dropping speed is 12ml / h) 20ml ethanol, magnetic stirring speed is 300r / min, after stirring for 10min, add 20ml distilled water, volatilize overnight, volatilize until the solution is 2ml, seal and store at 4°C.

[0044] Results: The average particle size of PLA-PEG nanoparticles or micelles or nanoparticle mixed micelles was 206±6.1nm.

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Abstract

The invention discloses a preparation method of a polyene-containing taxol nanoparticle mixed micelle preparation and a freeze-drying agent, which prepares docetaxel PLA-PEG nanoparticles or micelle or nanoparticle mixed micelle through a modified solvent evaporation method, takes PLA-PEG copolymer as a carrier, and wraps docetaxel in a PLA hydrophobic core. When in use, the docetaxel PLA-PEG containing long cycle freeze-dried preparation only needs to be added with water and is dissolved, and uniform nanoparticle suspension, micellar solution or mixed micellar nanoparticle suspension can be prepared. The preparation method does not need tween-80 and ethanol solubilization, only takes the biodegradable PLA-PEG as the carrier, and does not contain any surfactant; and compared with the docetaxel injection on sale, the preparation can reduce the toxicity and the adverse reactions of the medicine, and improve the clinical application safety of the medicine.

Description

technical field [0001] The invention relates to a preparation method of a nanoparticle mixed micelle preparation loaded with docetaxel and a freeze-drying agent. Background technique [0002] Docetaxel (DTX), also known as docetaxel, is a new type of anti-tumor drug developed in recent years, and it is the second generation of synthetic drugs in the class of paclitaxel. The mechanism of action of docetaxel is similar to that of paclitaxel, and its antitumor activity is 1.3 to 12 times that of paclitaxel. It plays an antitumor effect by interfering with the microtubule network necessary for cell mitosis and interphase cell functions. Docetaxel can bind to free tubulin, promote the assembly of tubulin into stable microtubules, and inhibit its depolymerization, resulting in the loss of normal function of microtubule bundles and the fixation of microtubules, thereby inhibiting cell mitosis . It is clinically used in breast cancer, non-small cell lung cancer, pancreatic cancer,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/00A61K9/19A61K31/337A61K47/34A61P35/00
Inventor 张娜刘东华刘志红
Owner SHANDONG UNIV
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