Synthetic method of targeted pegylated lipid medicinal material

Abstract

The invention relates to a synthetic method of a targeted pegylated lipid medicinal material, belonging to the technical field of synthesis of medicinal lipid materials. According to the synthetic method, lipid containing hydroxy is used as an initiating agent to directly induce polymerization of an epoxyethane monomer by an anionic polymerization method; by controlling the ratio of the epoxyethane monomer to the initiating agent, the pegylated lipid medicinal material with controllable molecular weight and molecular weight distribution is obtained by acidification and purification; the medicinal carrier material can realize long circulation in vivo; and targeted molecules can also be coupled by further modification, thus realizing a targeting functional in vivo. The medicinal lipid material obtained in the invention has the advantages of stable structure, simple synthesis processing steps, mild reaction conditions, low cost and easy realization of functional targeting ability.

Description

Technical field [0001] The invention relates to a synthesis technology of medicinal lipid materials, in particular to a method for synthesizing targeted pegylated lipid medicinal materials, and belongs to the technical field of medicinal lipid material synthesis. Background technique [0002] In recent years, driven by the rapid development of biomaterials and polymer chemistry, polymer materials with various functions have continuously emerged, prompting the rapid development of drug formulations and dosage forms, and entering the era of drug delivery systems (DDS). Make the development of long-acting, high-efficiency, targeted and other new drug delivery systems become the direction of pharmaceutical research and development. [0003] Polyethylene glycol (PEG) has the characteristics of good water solubility, biocompatibility, no antigen, and low toxicity. It is commonly used to modify phosphatidylcholine and fatty acid as auxiliary materials for preparing emulsions or liposomes...

AI Technical Summary

Problems solved by technology

[0004] There is an invention patent application with the patent application number 200610150050.3, which discloses that polyethylene glycol and cholesterol are linked by a small molecule of fatty acid. After research, it is found that the process of this method is complicated. The link between polyethylene glycol and cholesterol is an ester bond. Unstable under certain conditions, especially under alkaline conditions, the ester bond is easily broken

The length of its polyethylene glycol (PEG) chain cannot be self-controlled in the reaction, but a certain length of PEG chain must be added in the reaction; there is also an invention patent application with a patent application number of 200610168130.1, which discloses a compound that passes PEG through a small molecule As for the synthesis of sterol (ChoL) copolymer (PGC) by ether linkage, it is found through research that although the ether linkage structure is relatively stable, the process of preparing sterol and polyethylene glycol linkage by ether linkage is relatively complicated and costly; The polyethylene glycol chain also needs to be purchased, and its length cannot be self-controlled in the reaction, and a certain length of PEG chain must be added to the reaction; there is also a document [Hyperbranched polyglycerol-based lipids via oxyanionic polymerization: toward multifunctional stealth liposomes. Biomacromolecules. 2010, 11, 568-574] only had the synthesis of anionic PEGylated cholesterol and the preparation of blank liposomes, and did not involve the PEGylation of other lipid compounds, and there was no further research on the end groups of PEG. modify

The lipid materials prepared by the above methods not only have complicated preparation process and high production cost, but also have defects such as poor structural stability, uncontrollable length of PEG chain, and no active targeting of the carrier.

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