Purifying process of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA)

A technology of tetraazacyclocycle and purification method, which is applied in the field of purification of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, and can solve unreported, NaCl Mixing and other problems, to achieve the effect of low cost, simple equipment, simple operation process

Inactive Publication Date: 2012-09-12
WUHAN INSTITUTE OF TECHNOLOGY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But we found that the sodium salt of unacidified DOTA is difficult to separate out in the mixed solvent of water-ethanol. If a large amount of ethanol is added to make the product separate out as much as po

Method used

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  • Purifying process of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA)
  • Purifying process of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA)
  • Purifying process of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Weigh 10g DOTA·2HCl crude product, add it to a 250ml single-necked flask, add 100ml water, heat and stir to dissolve it fully, cool to below -10°C after the solution is clear and transparent, filter to obtain a white solid, transfer the white solid To a single-necked flask, add 50ml of water-ethanol with a volume ratio of 1:1, cool the solution to below -10°C after the solution is clear and transparent, filter to obtain a white solid, wash with ethanol and ether in turn, and obtain DOTA 2HCl after drying .

[0023] Make the above purified 2g DOTA·2HCl into 50ml aqueous solution, treat it with 20g 717 strong basic anion exchange resin, use purified water as the mobile phase to wash out the impurity NaOH, and the DOTA at this time is adsorbed on the resin , and finally with 2.0 molL -1 The product was washed out with HCl, and the solvent was removed to obtain high-purity DOTA with a yield of 55% and a purity of 99.69%.

[0024] The resulting DOTA and the standard 1 H N...

Embodiment 2

[0026] Weigh 10g DOTA·2HCl crude product, add it to a 250ml single-necked flask, add 100ml water, heat and stir to dissolve it fully, cool to below -10°C after the solution is clear and transparent, filter to obtain a white solid, transfer the white solid To a single-necked flask, add 50ml of water-ethanol with a volume ratio of 1:1, cool the solution to below -10°C after the solution is clear and transparent, filter to obtain a white solid, wash with ethanol and ether in turn, and obtain DOTA 2HCl after drying .

[0027] Make the above purified 2g DOTA·2HCl into 50ml aqueous solution, treat it with 20g 717 strong basic anion exchange resin, use purified water as the mobile phase to wash out the impurity NaOH, and the DOTA at this time is adsorbed on the resin , and finally with 1.0 molL -1 The product was washed out with HCl, and the solvent was removed to obtain high-purity DOTA with a yield of 58% and a purity of 99.71%.

Embodiment 3

[0029] Weigh 10g DOTA·2HCl crude product, put it into a 250ml single-necked flask, add 100ml of water-ethanol mixed solvent with a volume ratio of 1:0.1, heat and stir to fully dissolve it, and cool the solution to below -10°C after the solution is clear and transparent. Filter to obtain a white solid, transfer the white solid to a single-necked flask, add 50ml of water-ethanol with a volume ratio of 1:2, cool the solution to below -10°C after the solution is clear and transparent, filter to obtain a white solid, and successively wash with ethanol , ether, and dried to obtain DOTA·2HCl.

[0030]Make the above purified 2g DOTA·2HCl into 50ml aqueous solution, treat it with 20g 717 strong basic anion exchange resin, use purified water as the mobile phase to wash out the impurity NaOH, and the DOTA at this time is adsorbed on the resin , and finally use 0.02 molL -1 The product was washed out with HCl, and the solvent was removed to obtain high-purity DOTA with a yield of 65%. ...

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Abstract

The invention relates to a purifying process of DOTA. The process comprises the following steps: crystallizing DOTA.2HCl with a mixture of water and ethanol at a low temperature twice to remove an impurity NaCl to obtain refined DOTA.2HCl; and processing the refined DOTA.2HCl with a highly acidic cation or highly basic anion exchange resin to obtain high purity DOTA. The purifying process of the DOTA of the invention has the advantages of simplicity, easy implementation, economy and practicality, and is suitable for industrialized production.

Description

technical field [0001] The invention relates to a ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (1,4,7 , 10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid, referred to as DOTA) purification method. Background technique [0002] Gadoteric acid MRI contrast agent is a widely used clinical injection. It is a complex formed by Gd (Ⅲ) and DOTA. It has the characteristics of good water solubility, low osmotic pressure and stable chemical properties. It is used in angiography, venography and gastrointestinal contrast, but high-purity DOTA must be used to prepare gadoteric acid. Therefore, it is very necessary to study the purification method of DOTA. [0003] There are mainly two kinds of purification methods for DOTA reported in the literature: [0004] 1) Sherry proposed a DOTA purification method in the world patent WO8602,352. The crude DOTA was recrystallized using water-ethanol. However, DOTA purified by this method inevitably contains a small amount o...

Claims

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Application Information

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IPC IPC(8): C07D257/02
Inventor 柏正武周康陈伟奚江波季珉
Owner WUHAN INSTITUTE OF TECHNOLOGY
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