IP Library › Granted Patent US 12,144,892
Granted Patent B2
US 12,144,892 · App. 17/347,989 · Granted Nov 19, 2024

Pharmaceutical composition

Inventor: Shinji Okada (Tokushima, JP)
Assignee: TAIHO PHARMACEUTICAL CO., LTD.
A61K9/1652A61K9/1611A61K9/1694A61K31/47A61K31/04
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,144,892
App. No.
17/347,989
Granted
Nov 19, 2024
Kind
B2
Abstract

An object of the present invention is to provide a pharmaceutical composition which has excellent stability, disintegratability, and absorbability, is easily prepared, and contains 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof and a cyclodextrin derivative. The present invention relates to a pharmaceutical composition containing 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof and hydroxypropyl-β-cyclodextrin.

Claims (55)

1. A solid pharmaceutical composition, comprising:

a mixture of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof; and

hydroxypropyl-β-cyclodextrin;

wherein the composition includes peaks at chemical shift values [δ (ppm)] of 162.6, 130.4, 103.1, 82.7, 73.3, 41.9, and 19.9 in solid 13C-NMR.

2. The pharmaceutical composition according to claim 1 ,

wherein hydroxypropyl-β-cyclodextrin is contained at 0.1 to 5.5 parts by mass with respect to 1 part by mass of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof.

3. The pharmaceutical composition according to claim 1 ,

wherein hydroxypropyl-β-cyclodextrin is contained at 4.0 to 5.0 parts by mass with respect to 1 part by mass of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof.

4. The pharmaceutical composition according to claim 1 , further comprising:

a fluidizer selected from light anhydrous silicic acid, calcium silicate, magnesium aluminometasilicate, talc, aluminum silicate, and hydrated silicon dioxide.

5. The pharmaceutical composition according to claim 4 , wherein the fluidizer comprises from about 0.1 to 2 mass % of the total mass of the pharmaceutical composition.

6. The pharmaceutical composition according to claim 1 ,

wherein the amount of hydroxypropyl-β-cyclodextrin is from about 76 to 85 mass % of the pharmaceutical composition.

7. The pharmaceutical composition according to claim 1 ,

wherein the pharmaceutically acceptable salt is the mesylate and the composition includes peaks at 5 or more diffraction angles 2θ (±0.2°) selected from the group consisting of 6.5, 7.8, 9.6, 12.4, 18.8, 21.2, 23.0, 24.5, and 26.0 (°) in powder X-ray structure diffraction.

8. The pharmaceutical composition according to claim 1 ,

wherein the pharmaceutically acceptable salt is the mesylate and the composition includes peaks at 5 or more diffraction angles 2θ (±0.2°) selected from the group consisting of 6.5, 7.8, 9.6, 12.4, 18.8, 21.2, 23.0, 24.5, and 26.0 (°) in powder X-ray structure diffraction.

9. The pharmaceutical composition according to claim 1 ,

wherein the pharmaceutically acceptable salt is the mesylate and the composition includes peaks at 5 or more absorption bands selected from the group consisting of 1663, 1352, 1225, 1156, 1032, 720, and 553 (cm −1 ) in an infrared absorption spectrum.

10. A solid pharmaceutical composition, comprising:

4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof; and

hydroxypropyl-β-cyclodextrin;

wherein the composition includes peaks at 5 or more absorption bands selected from the group consisting of 1663, 1352, 1225, 1156, 1032, 720, and 553 (cm 1 ) in an infrared absorption spectrum.

11. The pharmaceutical composition according to claim 10 ,

wherein hydroxypropyl-β-cyclodextrin is contained at 0.1 to 5.5 parts by mass with respect to 1 part by mass of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition according to claim 10 ,

wherein hydroxypropyl-β-cyclodextrin is contained at 4.0 to 5.0 parts by mass with respect to 1 part by mass of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof.

13. The pharmaceutical composition according to claim 10 , further comprising:

a fluidizer selected from light anhydrous silicic acid, calcium silicate, magnesium aluminometasilicate, talc, and hydrated silicon dioxide.

14. The pharmaceutical composition according to claim 13 ,

wherein the fluidizer comprises from about 0.1 to 2 mass % of the total mass of the pharmaceutical composition.

15. The pharmaceutical composition according to claim 10 ,

wherein the amount of hydroxypropyl-Q-cyclodextrin is from about 76 to 85 mass % of the pharmaceutical composition.

16. The pharmaceutical composition according to claim 10 ,

wherein the pharmaceutically acceptable salt is the mesylate and the composition includes peaks at 5 or more diffraction angles 2θ (±0.2°) selected from the group consisting of 6.5, 7.8, 9.6, 12.4, 18.8, 21.2, 23.0, 24.5, and 26.0 (°) in powder X-ray structure diffraction.

17. The pharmaceutical composition according to claim 10 ,

wherein the pharmaceutically acceptable salt is the mesylate and the composition includes peaks at 5 or more diffraction angles 2θ (±0.2°) selected from the group consisting of 6.5, 7.8, 9.6, 12.4, 18.8, 21.2, 23.0, 24.5, and 26.0 (°) in powder X-ray structure diffraction.

18. The pharmaceutical composition according to claim 10 ,

wherein the pharmaceutically acceptable salt is the mesylate and the composition includes peaks at chemical shift values [δ (ppm)] of 162.6, 130.4, 103.1, 82.7, 73.3, 41.9, and 19.9 in solid 13C-NMR.

19. A pharmaceutical composition, comprising:

4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof; and

hydroxypropyl-β-cyclodextrin;

wherein the pharmaceutical composition is produced by physical mixing.

20. The pharmaceutical composition according to claim 19 ,

wherein the physical mixing is mixing, or a granulation.

21. The pharmaceutical composition according to claim 19 ,

wherein the physical mixing is mixing, a dry granulation method, or a wet granulation method.

22. The pharmaceutical composition according to claim 19 ,

wherein the physical mixing is a fluidized bed granulation method.

23. The pharmaceutical composition according to claim 19 ,

wherein the physical mixing does not include a step in which 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof is converted into a solution state when the pharmaceutical composition is produced.

24. The pharmaceutical composition according to claim 19 ,

wherein the pharmaceutical composition includes peaks at chemical shift values [δ (ppm)] of 162.6, 130.4, 103.1, 82.7, 73.3, 41.9, and 19.9 in solid 13C-NMR.

25. The pharmaceutical composition according to claim 19 ,

wherein the pharmaceutical composition includes peaks at 5 or more absorption bands selected from the group consisting of 1663, 1352, 1225, 1156, 1032, 720, and 553 (cm −1 ) in an infrared absorption spectrum.

Priority Claims (1)
JP 2017-026203 · Feb 15, 2017 · national
Continuity (2)
Continuation 16485971
Related Publication 20210308056A1 · Oct 7, 2021