Method for purifying contrast agent ioversol

A purification method, ioversol technology, applied in chemical instruments and methods, separation methods, carboxylic acid amide separation/purification, etc., can solve the problems of low overall yield of ioversol, further improvement, harsh purification conditions, etc. , to achieve the effects of easy production process amplification, large-scale industrial production, and short cycle

Pending Publication Date: 2022-05-13
XILING LAB CO LTD +1
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Problems solved by technology

Adding an appropriate amount of acetonitrile in the reaction solution can control the generation of alkoxy isomer impurities to a certain extent, but the purification conditions of this method are relatively harsh (120 ° C), and it takes a long time (more than 8 hours), and the obtained ioversol overall The yield is not high (57.0%~68.8%, with the starting material 5-hydroxyacetamido-N, N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1, 3-phthalamide), the purity (99.1~99.2%) also needs to be further improved

Method used

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  • Method for purifying contrast agent ioversol
  • Method for purifying contrast agent ioversol

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] The raw materials and equipment used in the present invention are all known products, all of which are obtained by purchasing commercially available products. The preparation of embodiment 1 ioversol pure product of the present invention

[0043] 1. Preparation of ioversol reaction solution

[0044]

[0045] Add N,N'-bis(2,3-dihydroxypropyl)-5-hydroxyacetamido-2,4,6-triiodoisophthalamide (Compound A, 10.00g) into a 100mL three-necked flask, purified water (30mL), 30% NaOH (3.15g, 1.8eq), after stirring and dissolving, add 2-chloroethanol (1.59g, 1.5eq), heat up to 40~50℃ and react for 4~5 hours, then add hydrochloric acid (1.5mL , concentration 36%~38%) to quench the reaction and adjust the pH to about 6.0~7.0, filter under reduced pressure through filter paper, and obtain the filtrate which is the quenched ioversol reaction solution. The yield is 85%~90%.

[0046] The obtained ioversol reaction solution was analyzed by high performance liquid chromatography (HPLC...

experiment example 1

[0050] Experimental example 1, the purity and related substance analysis of ioversol prepared by the present invention

[0051] 1. Experimental method

[0052] According to the preparation method of pure ioversol in Example 1, the only difference is that the filler and eluent of the macroporous adsorption resin in step 2 are replaced with the parameters shown in Table 1 to obtain each pure ioversol solution.

[0053] Then get above-mentioned each ioversol pure product solution and carry out HPLC analysis (according to Chinese Pharmacopoeia (2015 edition) in ioversol bulk drug method detection), with reference preparation (ioversol injection (Ansheli) Liebel-Flarsheim CompanyLLC, batch number J250A) is the control, and the results are shown in Table 1.

[0054] 2. Experimental results

[0055] Table 1 Process parameters and product test results of the purification of macroporous adsorption resin

[0056]

[0057] Note: in table 1, impurity A (%), impurity B (%), unknown i...

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Abstract

The invention discloses a method for purifying a contrast agent ioversol, which comprises the following steps: purifying an ioversol crude product solution through a macroporous adsorption resin packed column to obtain an ioversol pure product. The high-quality pure ioversol product is obtained by using the purification method, and the purity of the high-quality pure ioversol product is as high as 99.220%-99.619% and even higher than that of a reference preparation. In addition, the purification method disclosed by the invention is carried out at room temperature, and is low in cost, high in yield, easy in solvent recovery, large in batch, short in period, highly automatic in process, environment-friendly and pollution-free, easy in production process amplification and capable of realizing large-scale industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a method for purifying a contrast agent ioversol. Background technique [0002] The non-ionic water-soluble contrast agent is a contrast agent widely used clinically at present, and it is usually used in neuroradiography, angiography, intracerebral X-ray contrast, computerized tomography enhanced contrast, urography and the like. Compared with traditional ionic contrast agents, non-ionic contrast agents have attracted extensive attention due to the lower incidence of side effects and complications. [0003] However, compared with traditional ionic contrast agents, the synthesis steps and subsequent purification steps (especially the purification steps) of nonionic contrast agents are more complicated, because nonionic contrast agents are difficult to obtain from Crystallization out of aqueous solution, thus increasing the difficulty of purification. [0004] Ioversol i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C231/24C07C237/46B01D15/10B01D15/42
CPCC07C231/24B01D15/10B01D15/426C07C237/46
Inventor 龚家福吴京艾惜贾昊林黄金昆谢德建胡飞黄浩喜商国宁
Owner XILING LAB CO LTD
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