Preparation method and application of nanometer particles of taxane drugs

Abstract

The invention discloses a preparation method of a nanometer preparation of taxane drugs. The nanometer particles prepared by utilizing an emulsion diffusion method comprise the taxane drugs, copolymer carrier materials and emulgators. The preparation method comprises the steps of: dissolving the taxane drugs and the copolymer carrier materials into an organic phase mutually soluble with water, then dropwise adding the solution into a mixed solution of water in which the emulgators are dissolved and ethanol, stirring and mixing to form emulsion, and forming nanometer particles after removing organic solvents and solidifying. According to the nanometer particles prepared by utilizing the preparation method, the particle sizes are very uniform, the average particle size is 80-120 nm, the encapsulation efficiency is high, the stability is good, the preparation process is simple and controllable, and the scaled-up production is liable. The nanometer particles prepared by utilizing the preparation method can be applied to the treatment of malignant tumors and have obvious tumor inhibition effects.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and relates to polymer nanoparticles loaded with insoluble antitumor drugs, in particular to a preparation method and application of nanoparticles containing taxane-type insoluble antitumor drugs. Background technique

[0002] Taxane drugs mainly include paclitaxel and docetaxel, which are currently one of the most effective clinical antitumor drugs. Paclitaxel is a tetracyclic diterpenoid isolated from the bark of Pacific yew, with the molecular formula C 47 h 51 o 14 N, the molecular weight is 853.9, insoluble in water. Approved by the US FDA in 1992, its mechanism of action is to bind to cellular tubulin and promote tubulin polymerization to resist depolymerization and block mitosis, thereby inhibiting tumor growth and inducing tumor cell apoptosis. Clinical studies have confirmed that paclitaxel has a significant effect in the treatment of various solid tumors, including breast ...

Examples

Embodiment 1

[0035] Implementation example 1: Preparation of TPGS emulsified paclitaxel nanoparticles

[0036] 80mg PLGA (50:50, molecular weight 45000) and 8mg paclitaxel were dissolved in 20mL acetone solvent as oil phase, 240mgTPGS was dissolved in 40mL water and ethanol volume ratio is 1: 1 in the cosolvent of 1 forming mixed solution; Drop into the mixed solution containing TPGS at a speed of 1 min, and form a light blue nanoemulsion under low-speed stirring at 300 r / min. After the addition is completed, transfer the nanoemulsion to a rotary evaporator to remove the organic solvent by vacuum rotation to obtain nanoparticles. The average particle size measured by the laser dynamic scattering instrument is 105.1±2.3nm, and the particle size distribution is as follows: figure 1 As shown, the particle size distribution coefficient PDI is 0.047±0.025, and the encapsulation efficiency of nanoparticles is 92.5±2.2%. The morphology of the prepared nanoparticles was analyzed by transmission e...

Embodiment 2

[0037] Implementation example 2: Preparation of TPGS emulsified paclitaxel nanoparticles

[0038] 80mg PLGA (50:50, molecular weight 15000) and 8mg paclitaxel were dissolved in 20mL acetone solvent as oil phase, 240mgTPGS was dissolved in 40mL water and ethanol volume ratio is 1: 1 in the co-solvent of ethanol to form mixed solution; Drop into the mixed solution containing TPGS at a speed of 1 min, and form a light blue nanoemulsion under low-speed stirring at 300 r / min. After the addition is completed, transfer the nanoemulsion to a rotary evaporator to remove the organic solvent by vacuum rotation to obtain nanoparticles. The average particle size measured by the laser dynamic scattering instrument is 102.3±2.4nm, the particle size distribution coefficient PDI is 0.073±0.012, and the encapsulation efficiency of the nanoparticles is 85.2±2.4%.

Embodiment 3

[0039] Implementation example 3: Preparation of TPGS emulsified paclitaxel nanoparticles

[0040] 80mg PLGA (50:50, molecular weight 100000) and 8mg paclitaxel were dissolved in 20mL of acetone solvent as the oil phase, 240mgTPGS was dissolved in 40mL of water and ethanol with a volume ratio of 1:1 to form a mixed solution; the oil phase was dissolved in 1mL / Drop into the mixed solution containing TPGS at a speed of 1 min, and form a light blue nanoemulsion under low-speed stirring at 300 r / min. After the addition is completed, transfer the nanoemulsion to a rotary evaporator to remove the organic solvent by vacuum rotation to obtain nanoparticles. The average particle size measured by the laser dynamic scattering instrument is 109.1±2.2nm, the particle size distribution coefficient PDI is 0.062±0.018, and the encapsulation efficiency of the nanoparticles is 86.4±2.1%.

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and relates to polymer nanoparticles loaded with insoluble antitumor drugs, in particular to a preparation method and application of nanoparticles containing taxane-type insoluble antitumor drugs. Background technique

[0002] Taxane drugs mainly include paclitaxel and docetaxel, which are currently one of the most effective clinical antitumor drugs. Paclitaxel is a tetracyclic diterpenoid isolated from the bark of Pacific yew, with the molecular formula C 47 h 51 o 14 N, the molecular weight is 853.9, insoluble in water. Approved by the US FDA in 1992, its mechanism of action is to bind to cellular tubulin and promote tubulin polymerization to resist depolymerization and block mitosis, thereby inhibiting tumor growth and inducing tumor cell apoptosis. Clinical studies have confirmed that paclitaxel has a significant effect in the treatment of various solid tumors, including breast ...

Examples

Embodiment 1

[0035] Implementation example 1: Preparation of TPGS emulsified paclitaxel nanoparticles

[0036] 80mg PLGA (50:50, molecular weight 45000) and 8mg paclitaxel were dissolved in 20mL acetone solvent as oil phase, 240mgTPGS was dissolved in 40mL water and ethanol volume ratio is 1: 1 in the cosolvent of 1 forming mixed solution; Drop into the mixed solution containing TPGS at a speed of 1 min, and form a light blue nanoemulsion under low-speed stirring at 300 r / min. After the addition is completed, transfer the nanoemulsion to a rotary evaporator to remove the organic solvent by vacuum rotation to obtain nanoparticles. The average particle size measured by the laser dynamic scattering instrument is 105.1±2.3nm, and the particle size distribution is as follows: figure 1 As shown, the particle size distribution coefficient PDI is 0.047±0.025, and the encapsulation efficiency of nanoparticles is 92.5±2.2%. The morphology of the prepared nanoparticles was analyzed by transmission e...

Embodiment 2

[0037] Implementation example 2: Preparation of TPGS emulsified paclitaxel nanoparticles

[0038] 80mg PLGA (50:50, molecular weight 15000) and 8mg paclitaxel were dissolved in 20mL acetone solvent as oil phase, 240mgTPGS was dissolved in 40mL water and ethanol volume ratio is 1: 1 in the co-solvent of ethanol to form mixed solution; Drop into the mixed solution containing TPGS at a speed of 1 min, and form a light blue nanoemulsion under low-speed stirring at 300 r / min. After the addition is completed, transfer the nanoemulsion to a rotary evaporator to remove the organic solvent by vacuum rotation to obtain nanoparticles. The average particle size measured by the laser dynamic scattering instrument is 102.3±2.4nm, the particle size distribution coefficient PDI is 0.073±0.012, and the encapsulation efficiency of the nanoparticles is 85.2±2.4%.

Embodiment 3

[0039] Implementation example 3: Preparation of TPGS emulsified paclitaxel nanoparticles

[0040] 80mg PLGA (50:50, molecular weight 100000) and 8mg paclitaxel were dissolved in 20mL of acetone solvent as the oil phase, 240mgTPGS was dissolved in 40mL of water and ethanol with a volume ratio of 1:1 to form a mixed solution; the oil phase was dissolved in 1mL / Drop into the mixed solution containing TPGS at a speed of 1 min, and form a light blue nanoemulsion under low-speed stirring at 300 r / min. After the addition is completed, transfer the nanoemulsion to a rotary evaporator to remove the organic solvent by vacuum rotation to obtain nanoparticles. The average particle size measured by the laser dynamic scattering instrument is 109.1±2.2nm, the particle size distribution coefficient PDI is 0.062±0.018, and the encapsulation efficiency of the nanoparticles is 86.4±2.1%.

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