Liposome medicament containing cholesterol PEG modifier and preparation method thereof

Abstract

The invention relates to a liposome medicament containing a medicament serving as active component and the bimolecular layer of liposome which contains phosphatide, cholesterol and cholesterol PEG modifier, wherein the medicament is a vinblastine derivative. The liposome enables high entrapment rate of a medicament and prolongs detention time in human body.

Description

technical field [0001] The present invention relates to a liposome medicine, in particular, to a liposome medicine containing a cholesterol-containing PEG modified product, a preparation method thereof, and its use in the preparation of a medicine for treating tumor diseases. Background technique [0002] Liposomes can be used as carriers for many drugs. As a carrier of antitumor drugs (especially chemotherapeutic drugs), it can reduce the distribution of drugs in normal tissues and increase the accumulation of drugs in tumor tissues, thereby improving the therapeutic index of drugs. [0003] Traditional liposomes are easily recognized and phagocytosed by the immune system in the body, so the liposomes may have been cleared by the body before reaching the target area and unable to play their targeting role. Long-circulating liposomes, also known as stealth liposomes, can prevent the recognition and uptake of liposomes by macrophages, thereby prolonging the circulation time ...

AI Technical Summary

Problems solved by technology

[0006] However, we found in the process of preparing vinorelbine long-circulating liposomes that the addition of mPEG-DSPE will hinder the loading of vinorelbine. When the drug lipid ratio is high, mPEG-DSPE has a greater impact on vinorelbine Significantly, the encapsulation efficiency is less than 10%

According to the analysis, there are two reasons: ① In the traditional active drug loading technology, the drug is combined with the internal water phase anion (such as sulfate, citrate) to form a precipitate to obtain a higher encapsulation efficiency, while the weakly basic drug molecule , such as vinblastine and topoisomerase inhibitor compounds, have poor ability to form precipitation with anion in the aqueous phase of the liposome, so the retention capacity of the drug in the inner aqueous phase is poor, which affects the loading of the drug; ② positively charged Changchun When Ribine is loaded across the membrane driven by anion gradient and pH gradient, it preferentially binds to a large number of negatively charged mPEG-DSPE embedded on the outer surface of the phospholipid bilayer membrane. The power is enough to overcome the binding force between the drug and mPEG-DSPE, so that it can enter the aqueous phase of the liposome across the membrane; however, with the loading of the drug, the drug loading power gradually weakens, and the remaining drug is bound to the mPEG-DSPE and cannot enter Aqueous phase within the liposome, which reduces the efficiency of drug loading

Moreover, the mPEG-DSPE distributed on the inner surface of the phospholipid bilayer membrane will combine with the drug loaded in the inner water phase through the charge attraction, and then promote the leakage of the drug from the liposome, so as not to achieve sustained release and targeting. the goal of

[0007] From the above analysis, we can see that the addition of mPEG-DSPE not only affects the loading of the drug, but also promotes the leakage of the drug in the body, and its effect is more harmful than beneficial.

However, if it is not added, the circulation time of liposomes in the blood cannot be prolonged, and the purpose of slow release and synergistic effect cannot be achieved.

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