Paclitaxel freeze drying microemulsion for injection and method of producing the same

Abstract

The invention provides taxol freeze dried micro emulsion used for injection and a preparation method thereof. The freeze dried micro emulsion comprises taxol in effective dosage as the drug and pharmaceutic adjuvant such as oil phase, an emulsifier, an assistant emulsifier, a pH regulator, isotonic regulator and a freeze dried protective agent. The preparation method comprises the following steps: weighing the emulsifier in the amount according to the prescription, after evenly stirring the assistant emulsifier and oil for injection, adding the taxol into the mixed liquor and stirring for complete dissolution, then adding water for injection, completely stirring, obtaining taxol micro emulsion after regulating the pH value, further adding the freeze dried protective agent, and obtaining the freeze dried micro emulsion after vacuum freeze drying. Micro emulsion can be rapidly recovered by using physiologically compatible solution such as normal saline, glucose solution or Ringer's solution for dilution before use. The freeze dried micro emulsion and the preparation method are characterized in that through the further freeze drying technique to the taxol micro emulsion, the stability and the efficacy of the taxol are obviously enhanced, and the toxic and side effects are greatly reduced; especially, the freeze-drying method realizes very good protection function to the micro emulsion and avoids effusion of drug, thereby breaking through a new prospect for the establishment of stable dose pattern of a taxol micro emulsion drug loaded system and long-term preservation thereof. The preparation method for the freeze dried micro emulsion has the advantages of simple preparation technique, no organic solvent and low cost, therefore, the invention is suitable for industrialized mass production.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a freeze-dried microemulsion for injection containing paclitaxel and a preparation method thereof. Background technique [0002] Paclitaxel is a new and unique anti-microtubule drug, which is called one of the great discoveries in the past 20 years by the US New Compound Entity (NCE). It is one of the best drugs for the treatment of advanced ovarian cancer and breast cancer. In addition, they have also been found to have good curative effects on non-small cell lung cancer, prostate cancer, head and neck tumors, and rheumatoid arthritis. Due to the extremely poor water solubility of paclitaxel substances, the current clinical paclitaxel preparation is made of polyoxyethylene castor oil ( EL) is prepared by mixing 1:1 with absolute ethanol, which is diluted to the administration concentration with physiological saline or 5% glucose solution before injection. Since polyoxyethyle...

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Problems solved by technology

Because polyoxyethylene castor oil can cause severe allergic reactions in the body, the patient needs to be pretreated with anti-allergic drugs before administration. The whole process is very inconvenient, and the medication process needs to be carefully monitored, which has brought great pain to the patient.

[0003] to avoid The adverse reactions brought by EL and paclitaxel itself can improve the antitumor effect of paclitaxel. In recent years, domestic and foreign pharmaceutical workers have devoted themselves to the research of new drug delivery systems of paclitaxel, and the most successful one is to prepare it into liposomes, but in Drug precipitation can occur within a week of storage. The particle size of the liposome is between 4.5-5 μm, and there are particles larger than 30 μm, which may cause embolism when passing through capillaries after injection. Clinical application has certain risks. property; patent 200410068134.3 and 03134714.2 disclose paclitaxel emulsion, is that paclitaxel is mixed with injection oil, injection emulsifier and water for injection to make fat emulsion, this emulsion can overcome some defects of existing injection, and can supplement nutrition , but there are still disadvantages such as low drug loading, short storage time, poor stability, and the average particle size is about 500nm, which does not have good organ targeting; patent 99800022.1 discloses paclitaxel and water-insoluble derivatives - poly Although the composition of ethylene glycol 1000 vitamin E succinate improves the stability of paclitaxel to a certain extent, making it difficult to degrade in the carrier solution, the tolerance of the body to this preparation needs further study; patent 98811010.5 discloses the composition of paclitaxel and cyclodextrin, but cyclodextrin has a large allergic reaction and hemolysis, which limits the wide use of paclitaxel inclusion compound

Research on other paclitaxel preparations also includes polymer nanoparticles, solid lipid nanoparticles, and paclitaxel microsphere preparations and gels for local administration, but these preparations have drug leakage and drug burst release behavior in vivo to varying degrees. and the toxicity of polymers

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