Crystal form of Daprodustat, preparation method therefor and use thereof
Disclosed is crystal form M of the proline hydroxylase inhibitor daprodustat, wherein the X-ray powder diffraction thereof, expressed in 2θ angles and using Cu-Ka radiation, has characteristic peaks at 4.7±0.2°, 6.5±0.2°, and 6.8±0.2°. Disclosed are the preparation method for and the use of crystal form M. The crystal form M has good light stability, high temperature stability and high humidity stability, good solubility, and high purity.
1 . A crystal form of daprodustat, wherein an X-ray powder diffraction of the crystal form using Cu-Kα radiation has characteristic peaks at 2θ angles of 4.7±0.2°, 6.5±0.2° and 6.8±0.2°.
2 . The crystal form of daprodustat according to claim 1 , wherein the X-ray powder diffraction of the crystal form using Cu-Kα radiation further has a characteristic peak at 2θ angle of 20.7±0.2°.
3 . The crystal form of daprodustat according to claim 1 , wherein the X-ray powder diffraction of the crystal form using Cu-Kα radiation further has characteristic peaks at 2θ angles of 7.5±0.2° and 7.9±0.2°.
4 . The crystal form of daprodustat according to claim 1 , wherein the crystal form has the following X-ray powder diffraction pattern data:
2θ (±0.2°)
d (Å)
I %
4.7
18.9
27.7
6.5
13.7
15.7
6.8
13.0
100.
5 . The crystal form of daprodustat according to claim 1 , wherein the crystal form has the following X-ray powder diffraction pattern data:
2θ (±0.2°)
d (°A)
I %
4.7
18.9
27.7
6.5
13.7
15.7
6.8
13.0
100
7.5
11.7
4.8
7.9
11.1
3.4.
6 . The crystal form of daprodustat according to claim 1 , wherein the crystal form has the following X-ray powder diffraction pattern data:
2θ (±0.2°)
d (Å)
I %
4.68
18.88
27.7
6.45
13.69
15.7
6.81
12.97
100
7.55
11.70
4.8
7.95
11.11
3.4
10.77
8.21
1.6
15.27
5.80
3.5
16.63
5.33
1.6
17.49
5.07
1.5
20.67
4.30
9
21.67
4.09
2.2.
7 . The crystal form of daprodustat according to claim 1 , wherein the crystal form has an X-ray powder diffraction pattern substantially as shown in FIG. 1 .
8 . The crystal form of daprodustat according to claim 1 , wherein a differential scanning calorimetry curve of the crystal form has an absorption peak at 122.8±2° C.
9 . The crystal form of daprodustat according to claim 1 , wherein the crystal form has a differential scanning calorimetry curve substantially as shown in FIG. 2 .
10 . The crystal form of daprodustat according to claim 1 , wherein the crystal form has a thermal weight loss of less than 3.2% before 100° C. in a thermo gravimetric analysis curve.
11 . The crystal form of daprodustat according to claim 1 , wherein the crystal form has a thermo gravimetric analysis curve substantially as shown in FIG. 3 .
12 . A method for preparing the crystal form of daprodustat according to claim 1 , comprising the steps of: dissolving a crystal form CS1 of the daprodustat in n-butanol or isobutanol, adding an aqueous solution of sodium dodecyl benzenesulfonate and concentrating to obtain a solid, adding the solid into water for slurrying, filtering, and drying to obtain the crystal form of daprodustat.
13 . A pharmaceutical composition, comprising the crystal form of daprodustat according to claim 1 and a pharmaceutically acceptable excipient.
14 . A method for treating anemia, ischemia, or myocardial infarction in a patient in need thereof, comprising administering a pharmaceutically effective dose of the crystal form of daprodustat according to claim 1 or a pharmaceutical composition comprising the crystal form of daprodustat to the patient.
15 . The crystal form of daprodustat according to claim 1 , wherein the crystal form is crystal form M.
16 . The method according to claim 12 , wherein the crystal form of daprodustat is crystal form M.
17 . The pharmaceutical composition according to claim 13 , wherein the crystal form of daprodustat is crystal form M.
18 . The method according to claim 14 , wherein the crystal form of daprodustat is crystal form M.