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

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,...

Examples

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.

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,...

Examples

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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