Compound taxol and its derivative docetaxel fat emulsion and preparation method

Abstract

The invention relates to complex paclitaxel and its derivates docetaxel intralipid which includes the following ingredients: paclitaxel or docetaxel, vegetable oil, solubilizing agent, lecithin, glycerine, and water for injection at a ratio of 0.5-10:10-100:10-100:10-20:20-25:700-950. The preparing method includes the following steps: stirring with high speed homogenating machine or ultrasonic oscillating to get the protogala; preparing the complex paclitaxel intralipid with high pressure homogenizer. The preparation is intralipid in O/W type which packages paclitaxel or docetaxel into the compound oil phase. The compound oil phase has good solubility for paclitaxel or docetaxel which has prevented the phenomenon of precipitation after diluting the emulsion; the ingredients of compound oil has the function of coordinated antitumous effect; it can also release the injecting irritative response, haemolysis and hypersensitiveness; it has the function of targeting which has increased the drug action.

Description

technical field [0001] The invention relates to a fat emulsion of compound paclitaxel and its derivative docetaxel and a preparation method thereof. The preparation has good anticancer effect and belongs to the technical field of medicines. Background technique [0002] Paclitaxel is a chemical substance extracted from the plant yew. The English name is Paclitaxel. En-9-one-4,10-diacetate-2-benzoate-13-[(2'R,3'S)-N-benzoyl-3-phenylisoserine ester. Docetaxel is a derivative of paclitaxel, also known as docetaxel, the English name is Docetaxel. The chemical name is {2aR-[2aα, 4β, 4aβ, 6β, 9α(αR * , βs * ), 11α, 12α, 12aα, 12bα]}-β-{[(1,1-dimethylethoxy)carbonyl]amino}-α-carbonylphenylpropanoic acid [12b-acetoxy-12-benzoyl Oxy-2a, 3, 4, 4a, 5, 6, 9, 10, 11, 12, 12a, 12b-dodecahydro-4, 6, 11-trihydroxy-4a, 8, 13, 13-tetramethyl -5-Oxo-7,11-methylene-1H-cyclodecapenta[3,4]benzo[1,2-b]oxetan-9-yl]ester. Paclitaxel has a unique mechanism of action. It prevents the growth of tu...

AI Technical Summary

Problems solved by technology

Chinese patent 200510084055.6 A fat emulsion containing docetaxel and its preparation method describe the preparation method of docetaxel emulsion. In the preparation method of the emulsion, docetaxel is directly dissolved in the oil phase in this patent. It is known from the previous technology , docetaxel has low solubility in the oils listed in the patent, such as soybean oil, sesame oil, cottonseed oil, etc., such as soybean oil only dissolves 0.1mg / ml, etc. Therefore, the drug in the oil may be in a free state, and the It may affect the safety of injection emulsions. In addition, the patent does not involve the technical content of sharing with other active ingredients to improve drug efficacy and reduce toxicity

In the document Journal ofControlled Release58 (1999) 271-278, Pei Kan reported that tributyrin and tricaprylin were used as the oil phase, and under the action of emulsifier phospholipid and Tween 80, it was prepared into a fat emulsion, which could reach 0.75 The concentration of mg / ml can achieve better results, but this technology requires the addition of surfactant Tween 80, which may cause allergies and hemolysis, and this document does not involve the technical content of co-medication with other active ingredients. The data that paclitaxel is only 0.18mg / ml soluble in soybean oil and 0.23mg / ml in cottonseed oil are given in

Chinese patent 200410068134.3 A paclitaxel emulsion for intravenous injection and its preparation method describe the preparation method of paclitaxel emulsion. This patent directly dissolves paclitaxel in vegetable oil. Due to the low solubility of paclitaxel in oil, paclitaxel should be mostly suspended in oil. In the free state, after being prepared into an emulsion, it is easy to form a precipitate after dilution in clinical application. This patent does not involve the technology of combined drug use