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...

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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 pr

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