Crystal form of cenipride tartrate and preparation method thereof
By preparing four new crystal forms of cinipride tartrate, the shortcomings in existing technologies have been addressed, achieving high yield and stability, and supporting its further application.
Patent Information
- Application Number
- CN202511869479.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-11
- Publication Date
- 2026-02-24
AI Technical Summary
Existing technologies have limited research on the crystal form of cinipride tartrate and lack effective preparation methods, which restricts its further utilization.
Four new cinipride tartrate crystal forms (I, II, III, and IV) were prepared using different crystal systems and mixed solvents (methanol, methanol:water, and ethanol:water) combined with reflux heating and natural cooling. Their characteristic diffraction peaks were confirmed in XRD patterns using Cu-Kα radiation.
A high-yield preparation method was provided, ensuring the stability and purity of the cinipride tartrate crystal form and providing technical support for its further application.
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Figure CN121554411A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a crystal form of cinipride tartrate and its preparation method, belonging to the field of pharmaceutical crystal form technology. Background Technology
[0002] Cisipride tartrate, a benzamide derivative developed by Almirall Prodesfarma in Spain, is a novel and selective 5-hydroxytryptamine receptor agonist. It plays an important role in antagonizing the activity of dopamine receptors at cholinergic nerve endings and is highly effective in promoting gastrointestinal recovery. It is also rapidly absorbed after oral administration.
[0003] The structural formula of cimetidine tartrate is as follows:
[0004]
[0005] Cisipride tartrate is a polymorphic compound, but there is currently limited research on its crystal forms. Summary of the Invention
[0006] Through the study of different crystallization systems, this invention has discovered four previously unreported new crystal forms, which are intended to help further utilize cinipride tartrate.
[0007] This invention is implemented as follows:
[0008] A method for preparing cinnarizine tartrate crystal form I includes:
[0009] Weigh 20g of cinipride tartrate, add 240g of methanol, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the filter cake after drying is 19.3g, yield 96.5%, to obtain cinipride tartrate crystal form I product.
[0010] Using Cu-Kα radiation, in the powder XRD pattern expressed in 2θ angles, the cinipride tartrate crystal form I includes diffraction peaks at positions of 6.38°, 10.80°, 12.94°, 15.71°, 17.72°, 18.10°, 19.97°, 20.23°, 21.77°, and 24.91°, with a 2θ position error range of ±0.1°.
[0011] This invention also provides a method for preparing cinipride tartrate crystal form II, comprising:
[0012] Weigh 20g of cinipride tartrate, add 180g of a mixed solvent of methanol:water = 95:5, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.0g, with a yield of 95%, to obtain cinipride tartrate crystal form II product.
[0013] Using Cu-Kα radiation, in the powder XRD pattern expressed in 2θ angles, the cinipride tartrate crystal form II includes diffraction peaks at positions of 6.35°, 7.32°, 10.60°, 12.33°, 16.24°, 16.47°, 19.01°, 19.64°, 21.23°, and 25.95°, with a 2θ position error range of ±0.1°.
[0014] This invention also provides a method for preparing cinipride tartrate crystal form III, comprising:
[0015] Weigh 20g of cinipride tartrate, add 200g of a mixed solvent of methanol:water = 85:15, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.6g, with a yield of 98%, to obtain cinipride tartrate crystal form III product.
[0016] Using Cu-Kα radiation, in the powder XRD pattern expressed in 2θ angles, the cinipride tartrate crystal form III includes diffraction peaks at positions of 5.39°, 6.45°, 7.00°, 8.40°, 8.61°, 12.49°, 20.20°, 22.40°, 25.48°, and 26.09°, with a 2θ position error range of ±0.1°.
[0017] This invention also provides a method for preparing cisplatin tartrate crystal form IV, comprising:
[0018] Weigh 20g of cinipride tartrate, add 200g of a mixed solvent of ethanol:water = 85:15, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.0g, with a yield of 95%, to obtain cinipride tartrate crystal form IV product.
[0019] Using Cu-Kα radiation, in the powder XRD diffraction pattern expressed in 2θ angles, the cinipride tartrate crystal form IV includes diffraction peaks at positions of 6.35°, 7.32°, 10.60°, 12.33°, 16.24°, 16.47°, 19.01°, 19.64°, 21.23°, and 25.95°, with a 2θ position error range of ±0.1°.
[0020] This invention provides four new crystal forms of cinipride tartrate and their preparation methods, which can help further utilize cinipride tartrate. Attached Figure Description
[0021] Figure 1 The XRD pattern of cinipride tartrate crystal form I prepared according to an embodiment of the present invention is shown below.
[0022] Figure 2 The XRD pattern of cinipride tartrate crystal form II prepared according to an embodiment of the present invention is shown below.
[0023] Figure 3 The XRD pattern of cinipride tartrate crystal form III prepared according to an embodiment of the present invention is shown below.
[0024] Figure 4 The XRD pattern of cinipride tartrate crystal form IV prepared according to an embodiment of the present invention is shown. Detailed Implementation
[0025] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.
[0026] Example 1
[0027] A method for preparing cinnarizine tartrate crystal form I includes:
[0028] Weigh 20g of cinipride tartrate, add 240g of methanol, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the filter cake after drying is 19.3g, yield 96.5%, to obtain cinipride tartrate crystal form I product.
[0029] The powder XRD diffraction patterns, expressed in 2θ angles, using Cu-Kα radiation are shown in the table below:
[0030] 2θ strength relative strength 6.38 5657.13 43.11 10.80 13123.63 100.00 12.94 7402.03 56.40 15.71 6780.11 51.66 17.72 3995.95 30.45 18.10 7117.81 54.24 19.97 6535.62 49.80 20.23 11793.37 89.86 21.77 11841.31 90.23 24.91 9155.93 69.77
[0031] The XRD pattern is attached. Figure 1 .
[0032] Example 2
[0033] This embodiment provides a method for preparing cinnarizine tartrate crystal form II, including:
[0034] Weigh 20g of cinipride tartrate, add 180g of a mixed solvent of methanol:water = 95:5, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.0g, with a yield of 95%, to obtain cinipride tartrate crystal form II product.
[0035] The powder XRD diffraction patterns, expressed in 2θ angles, using Cu-Kα radiation are shown in the table below:
[0036] 2θ strength relative strength 6.35 4139.49 36.67 7.32 9049.15 80.16 10.60 5894.77 52.22 12.33 355.59 31.49 16.24 11289.41 100.00 16.47 4418.88 39.14 19.01 3702.94 32.80 19.64 8670.90 76.81 21.23 7871.55 69.73 25.95 8394.56 74.36
[0037] The XRD pattern is attached. Figure 2 .
[0038] Example 3
[0039] This embodiment provides a method for preparing cinipride tartrate crystal form III, including:
[0040] Weigh 20g of cinipride tartrate, add 200g of a mixed solvent of methanol:water = 85:15, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.6g, with a yield of 98%, to obtain cinipride tartrate crystal form III product.
[0041] The powder XRD diffraction patterns, expressed in 2θ angles, using Cu-Kα radiation are shown in the table below:
[0042] 2θ strength relative strength 5.39 1255.65 52.43 6.45 1022.34 42.68 7.00 685.03 28.60 8.40 2064.20 86.19 8.61 2395.08 100.00 12.49 1040.86 43.46 20.20 887.96 37.07 22.40 1210.81 50.55 25.48 873.99 36.49 26.09 843.98 35.24
[0043] The XRD pattern is attached. Figure 3 .
[0044] Example 4
[0045] This embodiment provides a method for preparing cinnidapride tartrate crystal form IV, including:
[0046] Weigh 20g of cinipride tartrate, add 200g of a mixed solvent of ethanol:water = 85:15, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.0g, with a yield of 95%, to obtain cinipride tartrate crystal form IV product.
[0047] The powder XRD diffraction patterns, expressed in 2θ angles, using Cu-Kα radiation are shown in the table below:
[0048] 2θ strength relative strength 6.35 4139.49 36.67 7.32 9049.15 80.16 10.60 5894.77 52.22 12.33 3555.59 31.49 16.24 11289.41 100.00 16.47 4418.88 39.14 19.01 3702.94 32.80 19.64 8670.90 76.81 21.23 7871.55 69.73 25.95 8394.56 74.36
[0049] The XRD pattern is attached. Figure 4 .
[0050] Although the present invention has been described herein with reference to illustrative embodiments, the above embodiments are merely preferred embodiments of the present invention, and the implementation of the present invention is not limited to the above embodiments. It should be understood that those skilled in the art can devise many other modifications and implementations, which will fall within the scope and spirit of the principles disclosed in this application.
Claims
1. A method for preparing cinipride tartrate crystal form I, characterized in that... include: Weigh 20g of cinipride tartrate, add 240g of methanol, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the filter cake after drying is 19.3g, yield 96.5%, to obtain cinipride tartrate crystal form I product.
2. Cynicipride tartrate crystal form I, characterized in that: Using Cu-Kα radiation, in the powder XRD pattern expressed in 2θ angles, the cinipride tartrate crystal form I includes diffraction peaks at positions of 6.38°, 10.80°, 12.94°, 15.71°, 17.72°, 18.10°, 19.97°, 20.23°, 21.77°, and 24.91°, with a 2θ position error range of ±0.1°.
3. A method for preparing cinipride tartrate crystal form II, characterized in that... include: Weigh 20g of cinipride tartrate, add 180g of a mixed solvent of methanol:water = 95:5, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.0g, with a yield of 95%, to obtain cinipride tartrate crystal form II product.
4. Cispyridaben tartrate crystal form II, characterized in that: Using Cu-Kα radiation, in the powder XRD pattern expressed in 2θ angles, the cinipride tartrate crystal form II includes diffraction peaks at positions of 6.35°, 7.32°, 10.60°, 12.33°, 16.24°, 16.47°, 19.01°, 19.64°, 21.23°, and 25.95°, with a 2θ position error range of ±0.1°.
5. A method for preparing cinipride tartrate crystal form III, characterized in that... include: Weigh 20g of cinipride tartrate, add 200g of a mixed solvent of methanol:water = 85:15, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.6g, with a yield of 98%, to obtain cinipride tartrate crystal form III product.
6. Cispyridaben tartrate crystal form III, characterized in that: Using Cu-Kα radiation, in the powder XRD pattern expressed in 2θ angles, the cinipride tartrate crystal form III includes diffraction peaks at positions of 5.39°, 6.45°, 7.00°, 8.40°, 8.61°, 12.49°, 20.20°, 22.40°, 25.48°, and 26.09°, with a 2θ position error range of ±0.1°.
7. A method for preparing cinipride tartrate crystal form IV, characterized in that... include: Weigh 20g of cinipride tartrate, add 200g of a mixed solvent of ethanol:water = 85:15, heat under reflux and stir until the solid is completely dissolved, remove the heat, allow to cool naturally to room temperature, continue stirring for 1 hour, filter, and the dried filter cake yields 19.0g, with a yield of 95%, to obtain cinipride tartrate crystal form IV product.
8. A crystalline form IV of cinnidapride tartrate, characterized in that: Using Cu-Kα radiation, in the powder XRD diffraction pattern expressed in 2θ angles, the cinipride tartrate crystal form IV includes diffraction peaks at positions of 6.35°, 7.32°, 10.60°, 12.33°, 16.24°, 16.47°, 19.01°, 19.64°, 21.23°, and 25.95°, with a 2θ position error range of ±0.1°.