Camptothecine and hydroxy camptothecine lipid composition and its preparing method

Abstract

The invention relates to anticancer drug camptothecin, hydroxycamptothecin lipid composition and a preparation method thereof. The advantage of the lipid composition of camptothecin and hydroxycamptothecin is that it can not only solve the water insolubility of the main drug, but also protect the active functional group δ lactone in the chemical structure of the main drug from opening the ring and affecting the curative effect.

Description

technical field [0001] The invention relates to a liposome freeze-dried powder preparation of active ingredients of camptothecin or hydroxycamptothecin and a preparation method thereof. technical background [0002] Camptothecin or hydroxycamptothecin and its derivatives are extracted and separated from Camptotheca acuminata Decne, a unique tree species in my country, and a series of derivatives are semi-synthesized using it as raw materials, which have broad-spectrum anticancer effects. Its anticancer activity is related to the action of topoisomerase and is a topoisomerase inhibitor. It is known that the content of topoisomerase in many tumor cells is higher than that in normal cells, and camptothecin or hydroxycamptothecin and their series of derivatives can inhibit topoisomerase and produce anticancer effects. However, due to its water insolubility and its important active functional group, the δ lactone ring, is unstable in the blood circulation, and the ring opens qui...

AI Technical Summary

Problems solved by technology

For example, topotecan is developed into liposomes by ion gradient method to protect its δ-lactone ring. The method is to make blank liposomes by freezing and thawing phospholipids five times repeatedly by ammonium sulfate gradient method, and then Encapsulate topotecan to form topotecan liposome, above two steps all need to adopt SephadexG-50 gel column chromatography to remove ammonium sulfate and free topotecan, this method is loaded down with trivial details, and the cycle is long, is not suitable for industrialized production (Anti -Cancer Drugs 2002, 13, pp.709-717); and irinotecan is developed into liposomes using the pH gradient method to protect its δ-lactone ring, which needs to be made into irinotecan under acidic conditions of pH3 Rinotecan liposomes, and then adjust the pH with alkali to generate a certain ΔPH (i.e. pH gradient) in the internal and external environment of the liposome and incubate with temperature for a certain period of time, and use this transmembrane ΔPH to encapsulate irinotecan in the liposome , this method is not simple and feasible (JOURNAL OF BIOSCIENCE AND BIOENGINEERING Vol 95, No.4,405-408.2003)

[0004] At present, the commercially available camptothecin or hydroxycamptothecin injection is made into a sodium salt to make a water-soluble water injection, but the stability of the solution is worse than that of the powder injection freeze-dried agent, and hydroxycamptothecin has been declared domestically. Alkaline sodium salt lyophilized powder injection can improve the stability during storage, but this hydroxycamptothecin sodium salt dosage form cannot protect its active group δ lactone ring