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Novel crystal form of rabeprazole sodium aquo-complex and preparation method of rabeprazole sodium aquo-complex

A technology of dex-rabeprazole sodium and rabeprazole sodium, which is applied in the field of new crystal forms of proton pump inhibitor drugs such as prazoles, can solve the problems of easy degradation, discoloration, poor stability, etc., and achieve high product purity, Low hygroscopicity, good stability effect

Active Publication Date: 2015-06-24
燃点(南京)生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Amorphous dex-rabeprazole sodium has strong hygroscopicity, poor stability, and is easy to degrade and change color. Therefore, it is very necessary to obtain a stable crystalline form of dex-rabeprazole sodium for drug development

Method used

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  • Novel crystal form of rabeprazole sodium aquo-complex and preparation method of rabeprazole sodium aquo-complex
  • Novel crystal form of rabeprazole sodium aquo-complex and preparation method of rabeprazole sodium aquo-complex
  • Novel crystal form of rabeprazole sodium aquo-complex and preparation method of rabeprazole sodium aquo-complex

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Dissolve 2.25 g of NaOH in 100 mL of methanol, add 20 g of dex-rabeprazole under stirring, and react at room temperature for 1 h. After the reaction was completed, suction filtered, the filtrate was taken, and concentrated to dryness under reduced pressure to obtain dex-rabeprazole sodium as a solid. Add the obtained solid into 50 mL of acetone, stir at 40~50°C to dissolve, filter to remove insoluble matter. Stir and crystallize at about 10°C for 8 h. Suction filtration, washing with acetone, and drying gave 16.2 g of a white solid with a chemical purity of 99.98% and an ee value of 99.99%.

[0057] This crystalline compound is analyzed by X-ray powder diffraction, and its X-ray diffraction pattern is shown in figure 1 , hereinafter referred to as the crystal form Z crystal, the data are listed in the following table 1, omitted in table 1 figure 1 For some other weaker peaks given in , the error of the 2θ diffraction angle is ±0.2°.

[0058] Table 1 X-ray powder dif...

Embodiment 2

[0064] Dissolve 0.56 g of NaOH in 20 mL of methanol, add 5 g of dex-rabeprazole under stirring, and react at room temperature for 1 h. After the reaction was completed, suction filtered, the filtrate was taken, and concentrated to dryness under reduced pressure to obtain dex-rabeprazole sodium as a solid. Add the obtained solid into 15 mL butanone, stir at 40~50°C to dissolve, filter to remove insoluble matter. Add a small amount of seed crystals, stir and crystallize at about 5°C for 8 h. Suction filtration, washing with butanone, and drying gave 4.5 g of a white solid with a chemical purity of 99.97% and an ee value of 99.98%.

[0065] The crystal form compound was analyzed by X-ray powder diffraction, and the result showed that the compound had the same crystal form as the compound in Example 1. See the specific X-ray powder diffraction pattern Figure 5 , and the data are listed in Table 2 below. Omitted in Table 2 Figure 5 For some other weaker peaks given in , the ...

Embodiment 3

[0068] Embodiment 3 Stability and hygroscopicity experiment

[0069] Take an appropriate amount of Z crystal form compound obtained in Example 1 of the present invention and amorphous dex-rabeprazole sodium, put it in a glass plate, and place it at 40°C and 75% humidity for 10 days, and take samples on the 0th, 5th, and 10th day respectively , to investigate the stability of two different forms of compounds, the inspection indicators are appearance, weight, and purity, and the results are shown in Table 3.

[0070] Table 3 Stability investigation results

[0071]

[0072] From the above experimental results, it can be found that amorphous dex-rabeprazole sodium has strong hygroscopicity, poor stability, and easy degradation and discoloration. The Z-type crystal of dex-rabeprazole sodium hydrate prepared in Example 1 of the present invention has good stability and low hygroscopicity, which is beneficial for long-term storage.

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Abstract

The invention relates to a novel crystal form of rabeprazole sodium aquo-complex and a preparation method of the novel crystal form. The novel crystal form is called the Z-type crystal. The Z-type crystal of the rabeprazole sodium aquo-complex is characterized in that in the X-ray powder diffraction pattern expressed by Cu-K alpha radiation and a 2theta+ / -0.2DEG diffraction angle, the Z-type crystal has characteristic diffraction peaks at 9.3, 10.7, 18.2, 19.6, 21.2, 23.0, 27.2 and 29.9.

Description

technical field [0001] The invention relates to a new crystal form of prazole proton pump inhibitor drugs, in particular to a new crystal form of dex-rabeprazole sodium hydrate and a preparation method thereof. Background technique [0002] At present, with the development of our society, environmental changes, population structure and changes in people's lifestyles, the incidence of peptic ulcer has gradually increased, and it has become a common and frequently-occurring disease that affects people's quality of life. h + / K + -ATPase inhibitors have become a very effective means of treating peptic ulcer, among which omeprazole, pantoprazole, esomeprazole and rabeprazole are the most widely used clinically. Rabeprazole, developed and marketed by Japan Eisai in 1991, is a partially reversible H + / K + -ATPase inhibitors that act on H + / K + - The 4 parts of ATPase, due to the increase in the number of binding targets, has a faster, longer-lasting and stronger acid-suppr...

Claims

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Application Information

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IPC IPC(8): C07D401/12A61K31/4439A61P1/04
CPCC07B2200/13C07D401/12
Inventor 陈建芳赵维秦勇金春苏晋沈国梁吴敏陆赛花王玉梅高瑞雪周自桂徐成白仁仁张超李波周超
Owner 燃点(南京)生物医药科技有限公司
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