Crystal form of Cefathiamidine compound and preparation method therefor

Patent metadata

Field	Value
Publication number	US-9637502-B2
Application number	US-201515304824-A
Country	US
Kind code	B2
Filing date	Nov 20, 2015
Priority date	Dec 31, 2014
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

A novel crystalline form of Cefathiamidine compound and its preparation method, characterizing in its X-ray powder diffraction pattern and differential scanning calorimetry thermogram. Dissolving Cefathiamidine compound with a purity of 98% or higher in a solvent at a temperature of 30˜45° C. to form a solution, whose concentration is controlled within 0.05˜0.2 g/mL, and then adding a solventing-out agent to the solution, wherein the amount of the solventing-out agent is 3˜5 times (in volume) of that of the solvent; followed by cooling the solution down to 0˜10° C. at a rate of 0.2˜1° C./min; continuing to stir for 1˜3 hours, and separating the obtained solid-liquid suspension to provide a novel crystalline form of Cefathiamidine compound after drying.

First claim

What is claimed is:

1. A crystallized Cefathiamidine, characterized in that, it has an X-ray powder diffraction pattern comprising characteristic diffraction peaks (expressed in degrees 2θ) at 7.26°±0.2°, 8.08°±0.2°, 10.38°±0.2°, 12.64°±0.2°, 13.96°±0.2°, 14.52°±0.2°, 16.60°±0.2°, 19.22°±0.2°, 20.04°±0.2°, 21.14°±0.2°, 21.84°±0.2°, and 22.74°±0.2°.

2. The crystallized Cefathiamidine according to claim 1 , characterized in that, it has a differential scanning calorimetry thermogram comprising a melting endothermic peak at 169.6±1° C. and a decomposing exothermic peak at 172.2±1° C.

3. A method for preparing a crystallized Cefathiamidine, characterized in that:
dissolving Cefathiamidine compound with a purity of 98% or higher in a solvent at a temperature of 30-˜45° C. to form a solution, whose concentration is controlled within 0.05-˜0.2 g/mL;
adding a solventing-out agent to the solution, wherein the amount of the solventing-out agent is 3-˜5 times (in volume) of that of the solvent;
cooling the solution down to 0-˜10° C. at a rate of 0.2-˜1° C./min;
stirring for 1-˜3 hours, and separating the obtained solid-liquid suspension to provide the crystallized Cefathiamidine after drying.

4. The method according to claim 3 , characterized in that, said solvent is one or more selected from the group consisting of methanol, ethanol and water.

5. The method according to claim 3 , characterized in that, said solventing-out agent is selected from one or more selected from the group consisting of n-propanol, isopropanol, n-butanol, cyclohexane and n-hexane.

6. The method according to claim 3 , characterized in that, said solventing-out agent is dropwise added within 3-˜6 hours.

7. The method according to claim 3 , characterized in that, the drying condition is: a temperature between 25 and ˜35, a vacuum with air-pressure between 0.08 and ˜0.1 MPa and a drying time between 4 and ˜8 hours.

Assignees

• Univ Tianjin
• Hainan Lingkang Pharmaceutical

Inventors

• Hao Hongxun
• Tao Linggang
• Sun Zhihong
• Hou Baohong
• Lv Jun
• Yin Qiuxiang
• Wang Yongli
• Gong Junbo
• Xie Chuang
• Bao Ying

Classifications

• C07D501/12

  Separation; Purification · CPC title

• C07D501/60 Primary

  with a double bond between positions 3 and 4 · CPC title

• C07D501/28

  with the 7-amino radical acylated by an aliphatic carboxylic acid, which is substituted by hetero atoms · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title