Pyrroloquinoline quinone B crystal form and preparation method therefor

Abstract

The present invention relates to the technical field of chemical drugs and crystal form processes, and to a pyrroloquinoline quinine B crystal form and a preparation method therefor. The present invention comprehensively characterizes the pyrroloquinoline quinine B crystal form by virtue of means such as X-ray powder diffraction analysis, thermo-gravimetric analysis, and differential scanning calorimetry analysis so as to find the fact that the pyrroloquinoline quinine B crystal form is high in crystallinity and low in hygroscopicity, and a regular crystal form can be formed, thereby facilitating process treatment and improvement of physical and chemical properties of a medicine, and improving the patent medicine performance. The preparation method for the pyrroloquinoline quinone B crystal form provided in the present invention is simple, easy to control, and high in reproducibility.

Claims

1. A crystal form B of pyrroloquinoline quinone, wherein the crystal form B of pyrroloquinoline quinone has characteristic diffraction peaks selected from the following group consisting of: 11.100.2, 20.160.2, 22.570.2, 26.140.2, and 29.950.2.

2. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the crystal form B of pyrroloquinoline quinone has further 3 or more characteristic diffraction peaks selected from the following group consisting of: 15.69, 16.52, 17.32, 18.64, 19.40, 20.53, 21.77, 24.05, 24.36, 25.42, 27.05, 27.60, 28.15, 29.37, 32.06, 33.96, 35.62, 36.97, and 38.090.2.

3. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the X-ray powder diffraction pattern of the crystal form B of pyrroloquinoline quinone is essentially as shown in FIG. 1.

4. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the thermogravimetric analysis pattern of the crystal form B has a decomposition temperature at 260 C.

5. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the crystal form B is an anhydrous crystal form.

6. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the thermogravimetric analysis pattern of the crystal form B of pyrroloquinoline quinone is essentially as shown in FIG. 2.

7. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the differential scanning calorimetry pattern of the crystal form B of pyrroloquinoline quinone is essentially as shown in FIG. 3.

8. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the infrared spectrum of the crystal form B has characteristic peaks at least at 3344 cm.sup.1, 3257 cm.sup.1, 2808 cm.sup.1, 2596 cm.sup.1, 1745 cm.sup.1, 1726 cm.sup.1, 1710 cm.sup.1, 1691 cm.sup.1, 1643 cm.sup.1, 1508 cm.sup.1, 1402 cm.sup.1, 1336 cm.sup.1, 1261 cm.sup.1, 1207 cm.sup.1, 1080 cm.sup.1, and 769 cm.sup.1.

9. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the infrared spectrum of the crystal form B of pyrroloquinoline quinone is essentially as shown in FIG. 4.

10. The crystal form B of pyrroloquinoline quinone of claim 1, wherein the hygroscopicity analysis of the crystal form B shows that one molecule of water at a relative humidity of 85-95% is adsorbed to form a monohydrate.

11. A method for preparing the crystal form B of pyrroloquinoline quinone of claim 1, comprising the steps of: pyrroquinoline quinine acid is placed in a vacuum drying oven at room temperature, and the temperature is raised, thereby obtaining the crystal form B of pyrroloquinoline quinone.

12. The method of claim 11, wherein the temperature is raised to 130-160 C.

13. The method of claim 11, wherein the time is kept for 3-5 hours after the temperature is raised.

Description

DESCRIPTION OF FIGURES

(1) FIG. 1 is an X-ray powder diffraction (XRPD) pattern of the PQQ crystal form B provided in Example 1.

(2) FIG. 2 is a thermogravimetric analysis (TG) pattern of the PQQ crystal form B provided in Example 1.

(3) FIG. 3 is a differential scanning calorimetry (DSC) pattern of the PQQ crystal form B provided in Example 1.

(4) FIG. 4 is an infrared spectrum (IR) chart of the PQQ crystal form B provided in Example 1.

(5) FIG. 5 is a hygroscopicity analysis (DVS) pattern of the PQQ crystal form B provided in Example 1.

DETAILED DESCRIPTION

(6) In order to make the objectives, technical solutions and advantages of the present invention more obvious, the present invention is further described in detail below with reference to the figures and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention, and not intended to limit the present invention.

Example 1

(7) 20.0 mg of PQQ acid was placed in a glass bottle. The open glass bottle was placed in a vacuum drying oven and heated to 140 C. for 5 h to give a 20.00 mg of crystal form B of pyrroloquinoline quinone with a yield of 100%. The crystal form B of pyrroloquinoline quinone is a red crystalline powder.

Example 2

(8) 20.0 mg of PQQ acid was placed in a glass bottle. The open glass bottle was placed in a vacuum drying oven and heated to 140 C. for 6 h to give a 20.00 mg of crystal form B of pyrroloquinoline quinone with a yield of 100%. The crystal form B of pyrroloquinoline quinone is a red crystalline powder.

Example 3

(9) 20.0 mg of PQQ acid was placed in a glass bottle. The open glass bottle was placed in a vacuum drying oven and heated to 140 C. for 5.5 h to give a 20.00 mg of crystal form B of pyrroloquinoline quinone with a yield of 100%. The crystal form B of pyrroloquinoline quinone is a red crystalline powder.

Example 4

(10) 20.0 mg of PQQ acid was placed in a glass bottle. The open glass bottle was placed in a vacuum drying oven and heated to 150 C. for 4.5 h to give a 20.00 mg of crystal form B of pyrroloquinoline quinone with a yield of 100%. The crystal form B of pyrroloquinoline quinone is a red crystalline powder.

Example 5

(11) 20.0 mg of PQQ acid was placed in a glass bottle. The open glass bottle was placed in a vacuum drying oven and heated to 150 C. for 5 h to give a 20.00 mg of crystal form B of pyrroloquinoline quinone with a yield of 100%. The crystal form B of pyrroloquinoline quinone is a red crystalline powder.

Example 6

(12) 20.0 mg of PQQ acid was placed in a glass bottle. The open glass bottle was placed in a vacuum drying oven and heated to 150 C. for 6 h to give a 20.00 mg of crystal form B of pyrroloquinoline quinone with a yield of 100%. The crystal form B of pyrroloquinoline quinone is a red crystalline powder.

(13) The crystal form B of pyrroloquinoline quinone provided by the present invention is characterized by solid-state methods, such as an X-ray powder diffraction (XRPD), a thermogravimetric analysis (TG), a differential scanning calorimetry analysis (DSC), an infrared (IR) analysis, and a hygroscopicity analysis (DVS).

(14) A solid sample of the crystal form B of pyrroloquinoline quinone obtained in Example 1 was subjected to the X-ray powder diffraction analysis using a Bruker D8 BdvBnce-type diffractometer from Brook Instrument Co., Ltd., Germany, using a Cu-K ray (=1.5418 ) with a voltage of 40 kV, a current of 40 mA, a step size of 0.02 degrees, and 0.1 second for each step. The analysis results were shown in FIG. 1.

(15) A solid sample of the crystal form B of pyrroloquinoline quinone obtained in Example 1 was subjected to the thermogravimetric analysis, using a TG20F3 type thermogravimetric analyzer from Naichi Scientific Instruments Co., Ltd., Germany, with an atmosphere was nitrogen and the heating rate was 10 degrees/minute. The analysis results were shown in FIG. 2.

(16) A solid sample of the crystal form B of pyrroloquinoline quinone obtained in Example 1 was subjected to the differential scanning calorimetry analysis, using a DSC 8500 differential calorimeter from Perkin Elmer Corporation of the United States, with an atmosphere of nitrogen and a heating rate of 10 degrees/minute. The analysis results were shown in FIG. 3.

(17) A solid sample of the crystal form B of pyrroloquinoline quinone obtained in Example 1 was subjected to an infrared spectrum analysis at room temperature using a Nicolet-MBgnB FT-IR 750 infrared spectrum analyzer from Nicololi Corporation of the United States, with a detection range of 4000-350 cm.sup.1 wavenumber. The analysis results were shown in FIG. 4.

(18) A solid sample of the crystal form B of pyrroloquinoline quinone obtained in Example 1 was subjected to a hygroscopicity analysis. The analysis results were shown in FIG. 5, from which it can be seen that at a relative humidity of 85-95%, the crystal form adsorbed a molecule of water and was converted into a monohydrate compound, which had a low water absorption rate and increased slowly, which indicates that the crystal form had a low hygroscopicity.

(19) The foregoing descriptions are merely preferred embodiments of the present invention, and not used to limit the present invention. Any modifications, equivalent replacements and improvements made within the spirit and principle of the present invention should be included in the protection scope of the present invention.