Separation and purification method of high-purity netilmicin

Abstract

The invention relates to a separation and purification method of high-purity netilmicin, belonging to the technical fields of medical continuous chromatographic separation and binding film separation and purification. In the invention, the continuous chromatographic separation technology is used for separating and purifying triacetyl sisomicin reaction liquid to obtain high-purity triacetyl sisomicin, and then, the industrial chromatographic separation and film separation combined technology is used for purifying and separating netilmicin hydrolyzate to obtain high-purity netilmicin. By adopting a continuous chromatographic separation system combined with film ultrafiltration and nanofiltration technology, the feed liquid of the triacetyl sisomicin and the netilmicin which are used as intermediates can be effectively separated and purified through the continuous chromatographic separation system; in the film separation production process, the reasonable temperature condition is controlled to reduce the generation of degradation products; and meanwhile, the production cost can be reduced, the production cycle can be shortened, the product quality can be improved, and the discharge amount of waste water can be lowered. The netilmicin purity of the product, which is measured by the high performance liquid chromatography (HPLC) method, is greater than or equal to 98%.

Description

technical field [0001] The present invention relates to a method for separating and purifying high-purity netilmicin, which mainly uses ultra- and nanofiltration membrane technology to reduce the generation of degraded substances of netilmicin and intermediates by controlling the temperature conditions in the purification process; and A method for obtaining high-purity netilmicin by separating and purifying by-products produced during the synthesis of netilmicin by using continuous chromatographic separation technology. The invention belongs to the technical field of membrane separation combined with continuous chromatographic separation and purification of organic compounds. Background technique [0002] Netilmicin is a semi-synthetic aminoglycoside antibiotic with strong antibacterial activity against aerobic Gram-negative bacilli, Escherichia coli, Pseudomonas aeruginosa, indole-negative and positive Proteus, Klebsiella Bacillus, Acinetobacter, Citrobacter, and some stra...

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Problems solved by technology

This production process has the disadvantages of low production capacity, low output, long production cycle, huge fixed investment, and large floor area.

[0007] 2) Due to the large amount of resin used, the amount of acid and alkali required to activate the resin is also large (including water). The unit acid consumption per kg of netilmicin is 30 kg of concentrated hydrochloric acid and 32 kg of liquid ammonia, and the discharge of wastewater is large, especially ammonia-containing waste water, environmental protection pressure is high

[0008] 3) Netilmicin, sisomicin, galamine, and 1,2-diethylnetilmicin are very similar in properties, and the separation effect is poor. In the resin desorption and absorption collection liquid, netilmicin and 1,2 - Diethyl netilmicin mixed liquid accounts for a large proportion; netilmicin collected liquid has low purity and a low pass rate at the first time, and it needs to be separated on the column repeatedly, and the yield is only 25%-30%

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