Irinotecan-cholesterol succinic acid simple lipid ion pair, liposome and preparation method and application thereof

Abstract

The invention discloses an irinotecan-cholesterol succinic acid simple lipid ion pair, a liposome and a preparation method and application thereof. The cholesterol succinic acid simple lipid is used as a counter-ionic agent, and the active proton of carboxyl in the cholesterol succinic acid simple lipid structure transfers to the nitrogen of irinotecan amino group, a coordination bond is formed, an ion pair is formed with irinotecan, so that the lipid solubility of irinotecan is improved, and the simple preparation method is easily used for packaging the drug on a phospholipid layer of the liposome, and the drug loading and packaging efficiency are improved. According to the irinotecan-cholesterol succinic acid simple lipid ion pair, the liposome and the preparation method and applicationthereof, the hydrophobic ion pair technology is combined with the nano drug delivery system, the lipid solubility of the insoluble drugs is improved, nano-preparations are developed, the complexity ofthe preparation process is simplified, and the irinotecan-cholesterol succinic acid simple lipid ion pair, the liposome and the preparation method and application thereof is conducive to expanding the industrial production. In addition, irinotecan ion pair and the liposome releases faster in the meta-acid environment, certain pH sensitivity is achieved, good antitumor effect and safety are achieved, and good application is achieved.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to an irinotecan-cholesterol succinate monoester ion pair, a liposome, a preparation method and an application. Background technique: [0002] Irinotecan (Irinotecan, CPT-11), chemical name 7-ethyl-10[4-(1-piperidinyl)-1-piperidinyl] carboxyoxycamptothecin, molecular formula C 33 h 38 N 4 o 6 , the relative molecular mass is 586.69. CPT-11 was first developed by Daiichi Seiyaku Company and Yakult Honsha Company in Japan. It was first launched in Japan in 1994 as a specific drug for the treatment of metastatic colorectal cancer. Listed in many countries, it is mainly used for the treatment of adult metastatic colorectal cancer and advanced (metastatic) pancreatic cancer. In addition, various indications such as gastric cancer, esophageal cancer, breast cancer, and extensive-stage small cell lung cancer are also under continuous development. [0003] Irinot...

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Problems solved by technology

[0010] Therefore, it can be understood that although irinotecan liposomes have great development prospects, there are still two problems: the first, irinotecan itself has poor water solubility, is unstable, and often exists in the form of hydrochloride trihydrate Although irinotecan hydrochloride has good water solubility, it needs to actively load drug by ion gradient method when preparing irinotecan liposome; the preparation process is relatively complicated, which is not conducive to industrial scale-up; For irinotecan liposomes, it is not known whether the drug can be encapsulated inside the liposome with a high encapsulation efficiency, and there are often problems with low drug loading and encapsulation efficiency

If the encapsulation efficiency is low, it is necessary to use necessary purification means to remove the unencapsulated drug in the process production, which further increases the complexity of the process.

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