Hydroxycamptothecine cubic liquid crystal precursor composition as well as preparation method and application thereof

Abstract

The invention discloses a hydroxycamptothecine cubic liquid crystal precursor composition as well as a preparation method and an application thereof, and belongs to the technical field of pharmacy. The composition is prepared from the following main raw materials in percentage by weight: 4 to 6% of hydroxycamptothecine, 50 to 78% of liquid crystal material, 2 to 8% of PEG, 1 to 3% of triolein, 2 to 7% of stearin, and 13 to 26% of dispersion medium, wherein the dispersion medium is prepared from the following raw materials in percentage by weight: 8 to 30% of an organic solvent which can be dissolved in water, and 70 to 92% of water. The composition can be continuously released in vitro for more than 30 days, so that the acting time of hydroxycamptothecine is greatly prolonged; and in addition, the local application mode is special, and thus, the effects of slowly releasing and targeting can be achieved synchronously.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a cubic liquid crystal precursor composition of hydroxycamptothecin and its preparation method and application. Background technique [0002] Hydroxycamptothecin is a tryptophan-terpene alkaloid isolated from Campylodontia involucratae, which inhibits DNA replication, transcription and mitosis by inhibiting DNA topoisomerase Ⅰ, thereby making tumor cells Lethal damage occurs, and it is mainly used clinically for malignant tumors such as gastric cancer, primary liver cancer, leukemia, rectal cancer, and bladder cancer. [0003] The antitumor activity of hydroxycamptothecin is closely related to its molecular structure. Closing the lactone ring is a necessary form to exert anticancer activity, and opening the lactone ring will greatly reduce or inactivate the activity. Studies have shown that the existing form of the camptothecin drug structure depends on the acidity and alkalini...

AI Technical Summary

Problems solved by technology

[0006] Some studies have made hydroxycamptothecin into liposomes or nanoparticles to prolong its circulation time in the body. However, due to the body's defense function, hydroxycamptothecin accumulates in the reticuloendothelial system in large quantities, and it is easy to damage the non-pathological reticulum. The endothelial system produces toxicity, and liposomes are colloidal drug delivery systems, which are prone to instability phenomena such as flocculation, aggregation, delamination, particle size increase, and drug leakage during placement; and the stability of nanoparticles in the solution phase Not high, hydroxycamptothecin is easy to precipitate, although the method of freeze-drying can improve the stability, but it is easy to reduce the encapsulation efficiency, the problem that the particle size of the nanoparticle becomes larger, and the preparation process of the nanoparticle is mostly carried out under alkaline conditions, Great influence on the stability of hydroxycamptothecin

[0007] In recent years, hydroxycamptothecin microemulsion is also a research hotspot, but the targeting of microemulsion is poor. The microemulsion system has certain irritation and safety, and whether it can maintain the original stability when diluted is an urgent investigation. The problem

In addition, although the double membrane structure of the vesicle can well contain hydroxycamptothecin and has good compatibility with the cell membrane, the fusion between the membranes of the vesicle is prone to occur, and its stability needs to be improved; hydroxycamptothecin Alkaline micelles how to avoid lysosomes and break through the barriers of the nuclear membrane after reaching the cells have yet to be resolved; although the carrier of solid lipid nanoparticles can reduce systemic toxicity, it is non-selective in important organs and lacks corresponding toxicity. Data is the problem with this drug delivery system

[0008] At present, the existing technology has not yet solved the pharmaceutical problems of poor stability and poor water solubility of hydroxycamptothecin, and the biopharmaceutical problem of short half-life of hydroxycamptothecin. In order to make the drug more stable and long-term in the blood In order to further improve drug efficacy and reduce adverse reactions, it is still necessary to study the drug delivery system to solve the limitations of the current hydroxycamptothecin carriers, and to find a more effective drug delivery system to supplement the drug delivery system. Its own defects, in order to solve the problem of its low clinical efficacy

Images