Novel dispersed system with docetaxel as main component

Abstract

The invention relates to a dispersion system with docetaxel as main component for injection, comprising a surfactant, an assistant surfactant and a specified amount of oil for injection. The volume ratio of oil phase to the surfactant is greater than 3 percent as well as less than and equal to 33 percent. The volume ratio of the assistant surfactant to surfactant is greater than or equal to 12.5 percent and less than 167 percent.

Description

technical field [0001] The invention relates to the technical field of medicine, and more specifically relates to a new dispersion system containing an anticancer drug docetaxel for intravenous infusion. technical background [0002] Docetaxel is a semi-synthetic novel paclitaxel derivative that reversibly preferentially binds to tubulin in microtubules by disrupting the dynamic balance between microtubules and tubulin dimers in eukaryotic cells The β subunit binds, induces and promotes the polymerization of tubulin into microtubules, and at the same time inhibits the depolymerization of the formed microtubules, resulting in stable microtubule bundles. Because the normal dynamic regeneration of microtubule bundles is blocked, cells cannot form normal mitotic spindles during mitosis, thereby inhibiting the mitosis and proliferation of cancer cells. [0003] Docetaxel has a broad anti-tumor spectrum and strong anti-tumor effect. It has outstanding curative effects on refracto...

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Problems solved by technology

[0004] Because docetaxel is almost insoluble in water, currently clinical use uses Tween-80 as a solvent and 13% ethanol as a special diluent. Due to the large proportion of Tween-80, the incidence of adverse reactions such as allergies is relatively low. high

[0005] In the public document 200510084055.6, a fat emulsion of docetaxel is disclosed, but its drug content is low, the highest drug content is only 1 mg / ml; the oil content is very high, and its oil content is 100 mg / ml. It is easy to cause fatty acids to accumulate in tissues and organs, and even affect the immune function of the body; the average particle size of the fat emulsion is 500nm, which does not have good organ targeting; the fat emulsion needs high temperature (110-121 ℃) in the preparation process ) sterilization, and the patent 02147245.9 has confirmed that docetaxel begins to degrade when heated to 40°C, and docetaxel is easily degraded at such a high temperature, which affects the quality of the drug

[0006] Publication 200610012102.0 discloses a docetaxel microemulsion. Although the above-mentioned shortcoming of the fat emulsion invented by publication 200510084055.6 is overcome, the particle diameter of the submicroemulsion obtained is less than 500nm, but the particle size distribution figure provided by it can be It is seen that the particle size of most particles is greater than 30nm, and there are still a small number of particles with a particle size greater than 220nm, which cannot pass through the microporous membrane during sterilization and filtration, and the active ingredient is lost during the preparation process; in addition, the preparation process requires heating (above 55°C) , and in this case docetaxel will still degrade, which will inevitably affect the quality of the drug

[0007] In the preparation process of the fat emulsion and submicron emulsion disclosed above, emulsification machinery such as high-pressure homogeneous emulsification, mechanical stirring emulsification, and colloid mill emulsification needs to be used, which requires additional equipment investment and the process is relatively complicated.

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