Method for synthesizing polysorbate-80 for injection

Abstract

The invention provides a method for synthesizing polysorbate-80 for injection, comprising the following steps: (1) taking sorbierite as a raw material, partially dehydrating the sorbierite under the conditions of an acid catalyst and a vacuum state, and carrying out crystallization and purification for three times on the dehydrated sorbierite to obtain primary high-purity dehydrated sorbierite II; (2) further dehydrating the high-purity primary dehydrated sorbierite II and then carrying out reduced pressure distillation and purification to obtain secondary high-purity dehydrated sorbierite III; (3) mixing the high-purity primary dehydrated sorbierite II with the high-purity secondary dehydrated sorbierite III in proportion to obtain high-purity dehydrated sorbierite IV; carrying out addition polymerization on the high-purity dehydrated sorbierite IV under the condition of a basic catalyst and ethylene oxide to obtain dehydrated sorbierite polyoxyethylene ether V; and (4) reacting the dehydrated sorbierite polyoxyethylene ether V with high-purity oleic acid under the action of an esterification catalyst and then refining the reactant of the dehydrated sorbierite polyoxyethylene ether V and the high-purity oleic acid to obtain the polysorbate-80 for injection. The liquid chromatogram (LC) of the polysorbate-80 for injection has two principal product peaks without other impurity peaks; and compared with the conventional craft products, the polysorbate-80 for injection is higher in purity, more stable in the technology, is controllable, meets the injection requirements in quality and has more reliable safety in clinical application.

Description

technical field [0001] The invention relates to a chemical synthesis method, in particular to a synthesis method of (high-purity) polysorbate-80 (I) for injection. Background technique [0002] Polysorbate-80 (I), also known as polyoxyethylene (20) sorbitan monooleate, it is a kind of hydrophilic nonionic surfactant, because it has better solubilizing effect, in When preparing injections of poorly soluble drugs, it is often used as a cosolvent, emulsifier and stabilizer. [0003] The synthetic method of (I) reported in the literature usually has the following two kinds: [0004] Method 1: Sorbitol and oleic acid undergo simultaneous dehydration and esterification reactions under the action of a basic catalyst to obtain sorbitan monooleate, and then condense with about 20 mole fractions of ethylene oxide to obtain polysorbate -80(I). [0005] Method 2: Sorbitol is first dehydrated under the action of an acidic or basic catalyst to obtain sorbitan, then esterified with olei...

AI Technical Summary

Problems solved by technology

[0011] The 5th, the polysorbate 80 (I) that above-mentioned method synthesizes has poor color and luster, is yellow to brownish yellow, does not meet the requirements for injection use;

[0012] Sixth, the desired active substance content is only 60-70%, and the content of by-products and impurities is high, which has limitations in pharmaceutical application and does not meet the requirements for injection use;

[0013] Seventh, the plasticity of the production operation is poor, and the product quality is not easy to control

[0014] The adverse reactions of some different traditional Chinese medicine injections in clinical use are mostly related to the use of low-quality, low-purity polysorbate 80 that does not meet the requirements for injection use

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