Crystals of quinolone derivatives
The present application relates to the field of medicine, and relates to crystals of quinoline derivatives, and in particular, to crystals of a quinoline derivative anhydride and a solvate, as well as a method for preparing the crystals, pharmaceutical compositions containing the crystals, and a use thereof in the field of medicine. The present application further provides a preparation method therefor, which has a high yield, has mild crystallization conditions, is suitable for industrial production, and may better meet the needs of the pharmaceutical industry.
1. A crystalline form of a compound of formula I or a solvate thereof, characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 3.27±0.2°, 6.56±0.2°, 8.84±0.2°, 9.95±0.2°, 10.52±0.2°, 13.10±0.2°, 13.15±0.2°, 15.58±0.2°, 16.68±0.2°, 17.84±0.2° and 18.66±0.2°;
or the solvate of the compound of formula I is an n-hexanol solvate of the compound of formula I, and a crystalline form of the n-hexanol solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 7.28±0.2°, 9.49±0.2°, 10.07±0.2°, 12.69±0.2°, 14.97±0.2°, 18.72±0.2°, 19.26±0.2°, 22.25±0.2°, 22.58±0.2° and 24.02±0.2°;
or the solvate of the compound of formula I is a dioxane solvate of the compound of formula I, and a crystalline form of the dioxane solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 7.23±0.2°, 9.48±0.2°, 10.41±0.2°, 13.34±0.2°, 14.79±0.2°, 18.03±0.2°, 19.89±0.2°, 22.45±0.2° and 23.50±0.2°;
or the solvate of the compound of formula I is an acetone solvate of the compound of formula I, and a crystalline form of the acetone solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diff action peaks at 2θ in degree of 7.21±0.2°, 8.94±0.2°, 9.58±0.2°, 10.81±0.2°, 14.65±0.2°, 15.18±0.2°, 16.82±0.2°, 17.54±0.2°, 18.16±0.2°, 19.93±0.2°, 20.60±0.2°, 22.16±0.2°, 24.17±0.2°, 24.91±0.2°, 27.54±0.2° and 27.59±0.2°; or the solvate of the compound of formula I is an ethyl acetate solvate of the compound of formula I, and a crystalline form of the ethyl acetate solvate is characterized by X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 7.48±0.2°, 9.71±0.2°, 10.70±0.2°, 12.52±0.2°, 13.30±0.2°, 13.51±0.2°, 15.08±0.2°, 15.65±0.2°, 17.08±0.2°, 18.47±0.2°, 20.15±0.2°, 21.63±0.2°, 22.77±0.2° and 23.84±0.2°;
or the solvate of the compound of formula I is a tetrahydrofuran solvate of the compound of formula I, and a crystalline form of the tetrahydrofuran solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 7.27±0.2°, 9.75±0.2°, 10.15±0.2°, 10.44±0.2°, 12.38±0.2°, 14.60±0.2°, 15.16±0.2°, 15.50±0.2°, 18.01±0.2°, 18.37±0.2°, 19.60=0.2°, 21.99±0.2°, 24.20±0.2° and 29.49±0.2°.
2. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the n-hexanol solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 7.28±0.2°, 9.49±0.2°, 10.07±0.2°, 12.37±0.2°, 12.69±0.2°, 14.97±0.2°, 15.66±0.2°, 16.29±0.2°, 17.25=0.2°, 18.24=0.2°, 18.72=0.2°, 19.26±0.2°, 21.15=0.2°, 22.25±0.2°, 22.58±0.2° and 24.02±0.2°.
3. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of a compound of formula I is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 3.27±0.2°, 6.56=0.2°, 8.20±0.2°, 8.84±0.2°, 9.95±0.2°, 10.52±0.2°, 13.10±0.2°, 13.15±0.2°, 15.58±0.2°, 16.68±0.2°, 17.84±0.2°, 18.66±0.2°, 19.96=0.29 20.19±0.2°, 22.68±0.2°, 23.12±0.2°, 24.82±0.2°, 25.37±0.2° and 27.22±0.2°.
4. The crystalline form of the compound of formula I or the solvate thereof of claim 3 , wherein the crystalline form of a compound of formula I is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 3.27+0.2°, 6.56±0.2°, 7.20±0.2°, 8.20±0.2°, 8.84±0.2°, 9.95±0.2°, 10.52±0.2°, 13.10±0.2°, 13.15±0.2°, 14.47±0.2°, 15.58±0.2°, 16.68±0.2°, 17.84±0.2°, 18.66±0.2°, 19.96±0.2°, 20.19±0.2°, 20.94±0.2°, 21.96±0.2°, 22.68±0.2°, 23.12±0.2°, 24.82±0.2°, 25.37±0.2°, 27.22±0.2°, 29.22±0.2°, 31.39±0.2°, 31.59±0.2°, 33.93±0.2° and 35.02±0.2°.
5. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the dioxane solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of about 7.23±0.2°, 9.48±0.2°, 10.41±0.2°, 11.04±0.2°, 12.28±0.2°, 13.34±0.2°, 14.79±0.2°, 15.00=0.2°, 15.48±0.2°, 16.17±0.2°, 16.96±0.2°, 17.49±0.2°, 18.03=0.29 19.58±0.2°, 19.89±0.2°, 21.34±0.2°, 22.45±0.2°, 23.50±0.2°, 24.71±0.2°, 25.04±0.2°, 26.77±0.2° and 30.18±0.2°.
6. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the acetone solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 7.21±0.2°, 8.94±0.2°, 9.58±0.2°, 10.81=0.2°, 13.07±0.2°, 14.65=0.2°, 15.18±0.2°, 16.82±0.2°, 17.54±0.2°, 18.16±0.2°, 18.88±0.2°, 19.93±0.2°, 20.60±0.2°, 21.02±0.2°, 22.16±0.2°, 24.17±0.2°, 24.91±0.2°, 25.81±0.2°, 27.54±0.2°, 27.59±0.2°, 29.16±0.2° and 29.75±0.2°.
7. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the ethyl acetate solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 7.48±0.2°, 9.71=0.2°, 9.98±0.2°, 10.70±0.2°, 12.52±0.2°, 13.30±0.2°, 13.51±0.2°, 15.08±0.2°, 15.65±0.2°, 17.08±0.2°, 17.75=0.2°, 18.47±0.2°, 19.57±0.2°, 20.15±0.2°, 21.63±0.2°, 22.77±0.2°, 23.31±0.2°, 23.84±0.2°, 24.85±0.2°, 25.26=0.2°, 25.79±0.2°, 26.19±0.2°, 26.93±0.2°, 29.11±0.2°, 29.65±0.2° and 30.36±0.2°.
8. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the tetrahydrofuran solvate is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree of 7.27±0.2°, 9.75±0.2°, 12.38±0.2°, 14.60±0.2°, 15.16±0.2°, 15.50±0.2°, 18.01±0.2°, 18.37±0.2°, 19.60=0.2°, 21.68±0.2°, 21.99=0.2°, 22.56±0.2°, 22.82±0.2°, 24.20±0.2°, 24.95±0.2°, 25.44±0.2°, 27.04±0.2°, 27.67±0.2°, 28.67±0.2°, 29.15±0.2°, 29.49±0.2° and 37.82±0.2°.
9. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of a compound of formula I is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, and the XRD pattern of the crystalline form E is as shown in FIG. 4 .
10. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of a compound of formula I is characterized by an X-ray powder diffraction pattern using Cu-Kα radiation, comprising diffraction peaks at 2θ in degree in the following Table:
Serial
Relative
number
2θ (°)
intensity (%)
1
3.27
92.7
2
6.56
55.5
3
7.20
2.9
4
8.20
15.0
5
8.84
88.3
6
9.95
100.0
7
10.52
78.5
8
13.10
29.3
9
13.15
28.4
10
14.47
2.4
11
15.58
30.7
12
16.68
58.1
13
17.84
60.1
14
18.66
65.5
15
19.96
13.2
16
20.19
13.5
17
20.94
25.1
18
21.96
9.0
19
22.68
61.0
20
23.12
60.9
21
24.82
31.4
22
25.37
42.5
23
27.22
32.2
24
29.22
7.3
25
31.39
2.3
26
31.59
4.8
27
33.93
2.4
28
35.02
3.2.
11. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the compound of formula I or the solvate thereof is present in a crystalline composition at 50% or more by weight of the crystalline composition.
12. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the compound of formula I or the solvate thereof is present in a crystalline composition at 70% or more by weight of the crystalline composition.
13. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the compound of formula I or the solvate thereof is present in a crystalline composition at 90% or more by weight of the crystalline composition.
14. The crystalline form of the compound of formula I or the solvate thereof of claim 1 , wherein the crystalline form of the compound of formula I or the solvate thereof is present in a crystalline composition at 95% or more by weight of the crystalline composition.
15. A pharmaceutical composition comprising an effective amount of the crystalline form of the compound of formula I or the solvate thereof of claim 1 or the crystalline composition thereof, and one or more pharmaceutically acceptable carriers.
16. A method for treating a tumor, comprising administering to a subject in need a therapeutically effective amount of the crystalline form of the compound of formula I or the solvate thereof of claim 1 , a crystalline composition comprising the same, or a pharmaceutical composition comprising the same, wherein the tumor is selected from the group consisting of:
liver cancer,
kidney cancer,
colon cancer gastrointestinal stromal tumor,
soft tissue sarcoma,
gastric cancer,
medullary thyroid cancer,
esophageal squamous cell carcinoma,
small-cell lung cancer,
non-small cell lung cancer,
endometrial cancer,
ovarian cancer,
cervical cancer, and
fallopian tube cancer.