Long circulation lipid nano-suspension containing docetaxel and preparation method thereof

Abstract

The invention discloses a long circulation lipid nano-suspension containing docetaxel. The nano-suspension is prepared from the following components in parts by weight: 0.5-50 parts of water solution, 0.5-50 parts of docetaxel, 0.05-20 parts of lipid-PEG (poly(ethylene glycol)) and 50-90 parts of phospholipid or is prepared from 0.5-50 parts of water solution, 0.5-50 parts of docetaxel, 0.05-20 parts of lipid-PEG, 50-90 parts of phospholipid and 0.01-10 parts of targeting factor with tumor targeting function. A preparation method of the nano-suspension comprises the following steps of: (1) dissolving phospholipid and lipid-PEG into the water solution to obtain solution A, or dissolving phospholipid, lipid-PEG and the targeting factor with tumor targeting function into the water solution to obtain solution A; (2) dispersing docetaxel into the solution A obtained in the step (1) to obtain suspension B; (3) carrying out high speed shearing on the suspension B for 1-3 minutes to obtain colostrum C; and (4) homogenizing the colostrum C by a high pressure homogenization method, thus obtaining the long circulation lipid nano-suspension. The preparation has the effects of increasing the content of docetaxel and reducing the toxic or side effect of docetaxel.

Description

Technical field [0001] The invention relates to a long-circulating lipid nano-suspension containing docetaxel, a targeted lipid nano-suspension and a freeze-dried preparation thereof, and a preparation method thereof, belonging to the technical field of medicine. Background technique [0002] Docetaxel (docetaxel) is a semi-synthesized taxane compound obtained from the precursor compound 10-deacetylbaccatin III extracted from European yew (Taxusbaccata L). The mechanism of action of docetaxel is similar to that of paclitaxel, and its anti-tumor activity is 1.3 to 12 times that of paclitaxel. It has a definite effect on common tumors such as breast cancer, non-small cell lung cancer and ovarian cancer. The structural formula of docetaxel is: C 43 H 53 NO 14 , The molecular weight is 807.88, and the structural formula is as follows: [0003] [0004] The solubility of docetaxel in water is very low, about 3μg / ml, and the oral bioavailability is poor, less than 8%. In order to improv...

AI Technical Summary

Problems solved by technology

[0004] The solubility of docetaxel in water is very low, about 3 μg / ml, and its oral bioavailability is poor, less than 8%. In order to improve its bioavailability, its injection is currently used clinically. Docetaxel injection, this type of preparation can be used only after being dissolved and diluted with 5% glucose injection or 0.9% sodium chloride injection before intravenous infusion

There are also solvents such as Tween 80 and ethanol in this type of preparation, which are prone to hemolysis and allergic reactions. Drugs such as dexamethasone need to be taken in advance for prevention and treatment, which is inconvenient for clinical use and has low drug safety.

Because docetaxel is easily oxidized and hydrolyzed in the solution for a long time, thereby reducing the content of the main drug docetaxel, the quality stability of the injection is poor

So far, there is no solution to the above problems

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