Novel long-circulating liposome composition and preparation method thereof

Abstract

The invention relates to a novel long-circulating liposome composition and an application method thereof. The long-circulating liposome composition is mainly prepared from phospholipid, cholesterol, an electronegative material and a long-circulating material serving as main raw materials, wherein tocopheryl acetate succinate or cholesterol succinate is used as the electronegative material particularly, and tocopheryl acetate polyethylene glycol succinate (TPGS) is used as the long-circulating material particularly, so that the stability of combining the long-circulating liposome composition and medicaments is improved; the long-circulating liposome composition can be used as a carrier of anti-tumor medicaments such as paclitaxel, docetaxel and 10-hydroxycamptothecine, and simultaneously, the tolerance is improved; and when the long-circulating liposome composition is used as the medicinal carrier, the circulating time of the carried medicaments in vivo is longer than that of various carriers sold on the market obviously, and the long-circulating liposome composition has the advantages of low cost and suitability for wide popularization and application.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a novel long-circulation liposome composition and its application. Background technique [0002] Paclitaxel is a natural product extracted from the bark, dry roots and branches of Taxus brevifolia Nutt. It is clinically used to treat ovarian cancer, breast cancer and non-small cell lung cancer. Its chemical structure is as follows: [0003] [0004] The chemical name is: 5β,20-epoxy-1,2α,4,7β,10β,13α-hexahydroxytaxane-11-en-9-one-4,10-diacetate-2-benzo Ester-13[(2'R,3'S)-N-benzoyl-3-phenylisoserine ester]. [0005] Because of its extremely low solubility in water (about 0.1 μg / ml), it is only dissolved in organic solvents such as methanol, ethanol, and dimethyl sulfoxide, which brings great difficulties to the intravenous administration of paclitaxel. Paclitaxel injection uses surfactant polyoxyethylene castor oil (Cremophor EL) and absolute ethanol (55:45, v / v) a...

AI Technical Summary

Problems solved by technology

[0007] However, the liposomes currently used have the disadvantages of poor in vitro stability and low drug loading: paclitaxel dispersed in the liposome phospholipid bilayer is easily affected by factors such as drug loading and temperature, and self-molecular The aggregation among them, and then generate needle-like drug crystals, which are precipitated into the aqueous solution; at the same time, in the stable range of paclitaxel liposomes, the molar ratio of general drugs to phospholipid materials is 1:30, which makes the drug-loading capacity of liposomes greatly reduce

In order to achieve the purpose of preparing long-circulating liposomes, the key is the selection and application of PEG materials, and polyethylene glycol 2000-distearoylphosphatidylethanolamine (PEG2000-DSPE) is the usual choice for long-circulating liposomes at present. PEGylated phospholipid material, which is used in the prescription of doxorubicin long-circulation liposome DOXIL, but PEG2000-DSPE is an artificially synthesized phospholipid material, the synthesis route is relatively complicated, the production cost is high, and the market price is expensive. In the prescription of long circulation liposome, the dosage of PEG2000-DSPE is at least 5% (molar ratio) of phospholipid total amount, just can play good long circulation effect, but because its molecular weight is 2790, so its actual mass ratio is relatively relatively Larger, which increases the production cost of long-circulating liposomes

And some studies have shown that some people use polyethylene glycol or polybehenyl ester or PEGylated cholesterol as long-term circulation materials, but they have not achieved good results.

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