Docetaxel liposome sterile lyophilized preparation and preparation method thereof

Abstract

The invention relates to a docetaxel liposome sterile lyophilized preparation and preparation method thereof, and the docetaxel liposome sterile lyophilized preparation comprises docetaxel, natural lecithin, PEG-DSPE, cholesterol, a protective agent for lyophilization, and buffer salts. The natural lecithin, PEG-DSPE, cholesterol, and docetaxel are dissolved in a organic solvent; a buffer solution containing the protective agent for lyophilization is added into mixed solution; the solution is incubated for 10-60 min for decreasing the average particle size of the liposome to 50-200 nm; and the preparation is obtained after bacilli-eliminated filtration and lyophilization. The docetaxel liposome prepared by the invention has the advantages of less toxic and side effect and higher curative effect when compared with commercially available ordinary injections at present. The preparation method of the invention is simple and practical, and is applicable to industrial production; and the prepared docetaxel liposome has high encapsulation efficiency and good stability.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a liposome sterile freeze-dried preparation of fat-soluble drug docetaxel and a preparation method thereof. Background technique [0002] Docetaxel (also known as docetaxel) injection, which was successfully developed by the French company Rhone-Planck-Anle in 1986, is another new type of anti-microtubule drug after paclitaxel. It was first launched in Mexico in April 1995. It was subsequently listed in Britain, the United States, France, Italy, Germany, Japan and other countries. [0003] Compared with paclitaxel, docetaxel has less efflux in and out of cells and has a significant effect of inducing apoptosis at low dose. Many in vitro and clinical studies have confirmed that docetaxel has a radiosensitizing effect on a variety of tumor cells and does not aggravate the radiation damage of normal tissues. The affinity of docetaxel is twice that of paclitax...

AI Technical Summary

Problems solved by technology

However, it did not investigate the stability of the liposome preparation after freeze-drying and reconstitution, especially the encapsulation efficiency and particle size of the drug after reconstitution.

In addition, the present invention has used sucrose, glucose and mannitol as the freeze-drying protection agent according to the disclosed method, but the freeze-dried product with better appearance cannot be obtained, and the liposome cannot be reconstituted after reconstitution, and the drug leakage is serious

[0017] CN101015547A discloses a new dosage form of docetaxel liposome and its preparation method, but its sterilization method adopts high-pressure sterilization at 121 degrees Celsius, which will undoubtedly cause a large amount of oxidation of phospholipids, and the stability of the drug is difficult to guarantee under this severe condition

In addition, the stability of the preparation after sterilization was not investigated

[0018] CN101317816A discloses a long-cycle preparation of docetaxel, which uses chloroform as a solvent, which is highly toxic and requires long-time rotary evaporation to remove residual solvents, which is difficult to implement in industrial production

In addition, the complex preparation process is not suitable for industrial production, especially when chloroform methanol is used as a solvent, which is highly toxic and difficult to completely remove, and the safety cannot be guaranteed.

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