Cabazitaxel drug composition and preparation method thereof

A technology of cabazitaxel and composition, which is applied in the field of cabazitaxel pharmaceutical composition, can solve the problems of protein nanoparticle stability damage, poor stability of protein nanoparticle, and impossibility, and achieve the effect of meeting the needs of intravenous drip therapy

Active Publication Date: 2013-11-20
QILU PHARMA HAINAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The inventor repeated the examples in the aforementioned patents many times, but the results described in the examples and instructions could not be achieved, especially in the process of removing small molecular compounds by dialysis and other methods, the stability of protein nanoparticles is poor, the reason It may be that organic solvents and protein denaturants exist in the nanoparticle suspension for a long time, and the stability of protein nanoparticles has been damaged before the small molecular compound is completely removed.

Method used

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  • Cabazitaxel drug composition and preparation method thereof
  • Cabazitaxel drug composition and preparation method thereof
  • Cabazitaxel drug composition and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Embodiment 1 High-pressure homogeneous emulsification method uses water-compatible solvent as organic phase solvent—control group

[0065] 600 mg of cabazitaxel was dissolved in 5 ml of absolute ethanol as the organic phase. 90ml of human serum albumin (6%, w / v) aqueous solution is the water phase. The mixture of aqueous and organic phases was homogenized at low speed for 2 minutes To prepare a crude emulsion, the crude emulsion was transferred to a high-pressure homogenizer (Microfulidics), homogenized for 5 cycles under the pressure of 3,000-30,000 psi, and the obtained liquid was transferred to a rotary evaporator, and reduced pressure at 40 °C (10-15KPa) evaporated for 30 minutes to remove absolute ethanol. The average diameter of cabazitaxel particles in the resulting dispersion was greater than 300 nm (Malvern Zetasizer).

Embodiment 2

[0066] Example 2 Preparation of nanoparticles smaller than 200 nm by high pressure homogeneous emulsification

[0067] This example describes the preparation of sterile filterable cabazitaxel particles. 300mg of cabazitaxel was dissolved in 1.35ml of chloroform and 0.15ml of absolute ethanol, the organic phase was added to 28.5ml (9.47%, w / v) of human albumin aqueous solution, and the mixture was heated at low speed. Shear and homogenize for 3 minutes A coarse emulsion was formed, transferred to a high pressure homogenizer (Microfulidics), and homogenized for 7 cycles at a pressure of 3,000-30,000 psi. The obtained medicinal solution was transferred to a rotary evaporator, and evaporated under reduced pressure (10-15KPa) for 30 minutes at 40°C to remove the organic solvent. The obtained dispersion suspension is translucent, the pH is 6.4, the Zeta potential is -26mv, and the average diameter of cabazitaxel particles is generally 120-160nm (Malvern Zetasizer). The dispersion...

Embodiment 3

[0070] Example 3 Nanoparticles smaller than 200 nm that can be sterile filtered by high pressure homogeneous emulsification method

[0071] 300mg of cabazitaxel was dissolved in 1.5ml of chloroform and 0.15ml of absolute ethanol, the organic phase was added to 23.35ml (12.85%, w / v) of human albumin aqueous solution, and the mixture was heated at low speed. Shear and homogenize for 3 minutes A coarse emulsion was formed, transferred to a high pressure homogenizer (Microfulidics), and homogenized for 8 cycles at 3,000-30,000 psi pressure. The obtained medicinal solution was transferred to a rotary evaporator, and evaporated under reduced pressure (10-15KPa) for 30 minutes at 40°C to remove absolute ethanol and chloroform. The obtained dispersion suspension is translucent, the pH is 6.5, the Zeta potential is -25mv, and the average diameter of the cabazitaxel particles is generally 120-160 nm (Malvern Zetasizer). The dispersion suspension was passed through a 0.22 μm microporo...

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Abstract

The invention provides a drug composition of cabazitaxel and a pharmaceutically acceptable biological carrier and a preparation method thereof. The cabazitaxel drug composition is actually a nanoparticle colloid dispersing system containing cabazitaxel. Cabazitaxel is encapsulated in a polymer shell made of proteins or is associated with the proteins by way of association to form nanoparticles, wherein the mass ratio of the cabazitaxel to the proteins is 1:(8-15); the pH value ranges from 5.0 to 7.0; the average diameter of the particles is not more than 200nm; the Zeta potential ranges from minus 10mv to minus 30mv; and the particles can be subjected to sterile filtration. The composition can be prepared by a high-pressure homogenating method or a protein denaturation and renaturation method. The composition prepared by the invention can be transformed to re-dispersable cakes or powder, can maintain stability for at least 48 hours at 37 DEG C after being re-dispersed in an aqueous medium, and can meet the requirements of intravenous drip therapy.

Description

technical field [0001] The invention relates to a cabazitaxel pharmaceutical composition and a preparation method of a particulate carrier that can be used for intravenously administering a pharmacologically active substance cabazitaxel. The cabazitaxel pharmaceutical composition in the present invention is actually a cabazitaxel-containing nanoparticle colloidal dispersion system. Cabazitaxel is encapsulated in a polymer shell made of protein or combined with protein in an associative manner to form nanoparticles, the pH is between 5.0 and 7.0, and the average particle diameter is not greater than 200 nm. The preparation of the colloidal systems of the present invention does not require the use of conventional surfactants or any polymeric core matrix and can be sterile filtered. Background technique [0002] Cabazitaxel, English name CABAZITAXEL, its chemical name is 4-acetoxy-2α-benzoyloxy-5β, 20-epoxy-1-hydroxy-7β, 10β-dimethoxy-9-oxygen Substituted taxane-11-en-13α-yl(...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/337A61K9/16A61K47/42A61K47/48A61P35/00
Inventor 李霞周志超杨清敏王栋海张明会
Owner QILU PHARMA HAINAN
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