Solid-phase load method for synthesizing polyethylene glycol-12-hydroxystearate

Abstract

The invention discloses a solid-phase load method for synthesizing polyethylene glycol-12-hydroxystearate. The solid-phase load method is specifically implemented through the following steps: a, loading polyethylene glycol on a chloromethylated polystyrene crosslinked resin; b, cleaning the resin on which the polyethylene glycol is immobilized by use of water; c, carrying out an esterification reaction of the polyethylene glycol immobilized on the resin and 12-hydroxystearate under the catalysis of an acid; d, cleaning the resin by use of an eluent; e, performing extraction, washing and spin evaporation on the eluate, thereby obtaining the product, namely the polyethylene glycol-12-hydroxystearate. The polyethylene glycol-12-hydroxystearate can be controllably synthesized by use of the solid-phase load method, and meanwhile, the product is excellent in color and yield.

Description

technical field [0001] The invention discloses a method for synthesizing polyethylene glycol-12-hydroxystearate by a solid-phase loading method, and belongs to the field of chemical synthesis. [0002] Background technique [0003] Polyethylene glycol-12-hydroxystearate, its structural formula is as follows: [0004] [0005] It can be used as a solubilizer and emulsifier in pharmaceutical preparations. An ideal drug should have good biosolubility and bioavailability when entering the body. However, among the drugs produced according to the prior art, 40% of the candidate drugs have solubility problems. To prepare suitable preparations for insoluble drugs, the problem of low solubility must first be solved. More than one-third of the workload in the drug development process is devoted to improving the solubility and bioavailability of poorly soluble drugs. Therefore, increasing the solubility or dissolution rate of poorly soluble drugs is one of the toughest challenge...

AI Technical Summary

Problems solved by technology

The ethylene oxide ethoxylation method is an industrial synthesis method of polyethylene glycol fatty acid ester. It has the advantages of fast reaction and good product appearance. The disadvantage is that it is difficult to control the molecular weight distribution, the reaction is violent, and it has high requirements for equipment; directly The esterification method is the esterification reaction of polyethylene glycol and fatty acid under the action of a catalyst, but there are serious defects in this method: the color of the product is dark and difficult to control, and the product is usually a mixture of monoester and diester. For pure monoester products, it is difficult to separate single and double esters; one of the transesterification methods is to react quantitative polyethylene glycol with boric acid to form boric acid polyethylene glycol monoester, and then mix this monoester with fatty acid. Under the action of a catalyst, a transesterification reaction occurs to obtain polyethylene glycol fatty acid ester. The defect of this method is that the formation of boric acid monoester cannot be well controlled, and it is still possible to generate double boric acid monopolyethylene glycol ester, i.e. polyethylene glycol The hydroxyl groups at both ends are esterified with boric acid, so that the obtained polyethylene glycol diester is still obtained by transesterification; another transesterification method is to obtain fatty acid methyl ester first, and then carry out transesterification with polyethylene glycol , based on the same reason, the hydroxyl groups at both ends of polyethylene glycol have the same reactivity, and they can all participate in the transesterification reaction at the same time, and the obtained product is still a mixture of monoester and diester. mixed problem

Images