Salt or polymorphic form of imidazo [1, 2-a] pyridine compound

Abstract

The invention provides a salt of a compound shown in a formula (I) or a polymorphic substance thereof, and the salt or the polymorphic substance thereof has excellent druggability, such as good solubility, illumination stability, bioavailability and the like.

Description

[0001] This application claims the right of priority from the following prior patent applications:

[0002] A prior application filed by the applicant with the State Intellectual Property Office of China on December 18, 2023, with the patent application number 202311742941.8 and the title "Salt of imidazo[1,2-a]pyridine compound or its polymorph".

[0003] The entire text of the above prior patent application is incorporated into this application by reference. Technical Field

[0004] The present invention relates to the field of pharmaceuticals, and particularly to salts of imidazo[1,2-a]pyridine compounds or their polymorphs. Background Art

[0005] (Azetidin-1-yl)(8-(2,6-dimethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridin-6-yl)methanone (Zastaprazan, the structure is shown in formula (I)), is an innovative potassium-competitive acid blocker (P-CAB), and is currently conducting a Phase III clinical trial for erosive esophagitis in South Korea. Existing data show that Zastaprazan has the advantages of rapid onset, good acid suppression effect, long-lasting action, and few adverse reactions, and can be extended to the treatment of duodenal ulcer, Helicobacter pylori infection, and non-erosive gastroesophageal reflux disease in the future.

[0006] Zastaprazan developed by CheilJedang Corporation is an oral dosage form. Although it has application potential in various indications, for some patients, such as those with dysphagia, vomiting, acute upper gastrointestinal bleeding, acute gastroenteritis, and patients in the recovery period after surgery, since they cannot be administered through the oral route, Zastaprazan will not be able to exert its efficacy in these patients, and the intravenous injection route becomes the preferred method for these patients.

[0007] However, the inventors found during the research process that the solubility of Zastaprazan and its citrate is extremely low, which is not conducive to the development of injection preparations.

[0008] Based on the above problems, it is necessary to further develop new salt forms with high solubility and good stability to provide better options for the development of this drug. Summary of the Invention

[0009] To solve the above technical problems, the present invention provides a salt of the compound shown in formula (I) or its polymorph; preferably, the salt is phosphate, sulfate, tartrate, malonate, 1,2-ethanedisulfonate, p-toluenesulfonate, hydrochloride, mesylate, hydrobromide, malate or fumarate;

[0010]

[0011] According to an embodiment of the present invention, the salt is phosphate, sulfate, hydrochloride.

[0012] According to an embodiment of the present invention, the salt is malonate, 1,2-ethanedisulfonate, hydrobromide or malate.

[0013] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the phosphate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1° ± 0.2°, 10.8° ± 0.2°, 11.5° ± 0.2°, 17.6° ± 0.2°, 22.0° ± 0.2°, 22.6° ± 0.2°; preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1° ± 0.2°, 10.8° ± 0.2°, 11.5° ± 0.2°, 15.9° ± 0.2°, 16.8° ± 0.2°, 17.6° ± 0.2°, 22.0° ± 0.2°, 22.6° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the phosphate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 11.8° ± 0.2°, 19.4° ± 0.2°, 19.8° ± 0.2°, 21.1° ± 0.2°, 23.1° ± 0.2°, 23.9° ± 0.2°, 24.5° ± 0.2°, 25.3° ± 0.2°, 26.9° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the phosphate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 23.1° ± 0.2°, 25.3° ± 0.2°, 26.9° ± 0.2°.

[0014] Preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1° ± 0.2°, 10.8° ± 0.2°, 11.5° ± 0.2°, 15.9° ± 0.2°, 16.8° ± 0.2°, 17.6° ± 0.2°, 22.0° ± 0.2°, 22.6° ± 0.2°, 23.1° ± 0.2°, 25.3° ± 0.2°, 26.9° ± 0.2°; Preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1° ± 0.2°, 10.8° ± 0.2°, 11.5° ± 0.2°, 15.9° ± 0.2°, 16.8° ± 0.2°, 17.6° ± 0.2°, 21.1° ± 0.2°, 22.0° ± 0.2°, 22.6° ± 0.2°, 23.1° ± 0.2°, 25.3° ± 0.2°, 26.9° ± 0.2°; According to an embodiment of the present invention, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1° ± 0.2°, 10.8° ± 0.2°, 11.5° ± 0.2°, 11.8° ± 0.2°, 15.9° ± 0.2°, 16.8° ± 0.2°, 17.6° ± 0.2°, 19.4° ± 0.2°, 19.8° ± 0.2°, 21.1° ± 0.2°, 22.0° ± 0.2°, 22.6° ± 0.2°, 23.1° ± 0.2°, 23.9° ± 0.2°, 24.5° ± 0.2°, 25.3° ± 0.2°, 26.9° ± 0.2°.

[0015] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 10.8° ± 0.2°, 11.5° ± 0.2°, 17.6° ± 0.2°, 21.9° ± 0.2°, 22.0° ± 0.2°, 22.6° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the phosphate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 8.1° ± 0.2°, 15.9° ± 0.2°, 16.8° ± 0.2°, 23.1° ± 0.2°, 25.3° ± 0.2°, 26.9° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the phosphate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 7.9° ± 0.2°, 11.8° ± 0.2°, 18.0° ± 0.2°, 19.4° ± 0.2°, 19.8° ± 0.2°, 21.1° ± 0.2°, 23.9° ± 0.2°, 24.5° ± 0.2°, 27.5° ± 0.2°, 32.9° ± 0.2°.

[0016] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the phosphate crystal form are shown in Table 1, wherein the error range of 2θ of each characteristic diffraction peak is ±0.2°. According to an embodiment of the present invention, the phosphate crystal form has an X-ray powder diffraction pattern substantially as Figure 1 shown. According to an embodiment of the present invention, the differential scanning calorimetry curve of the phosphate crystal form contains an endothermic peak at 206.9°C ± 3°C. According to an embodiment of the present invention, the differential scanning calorimetry curve of the phosphate crystal form is as Figure 2 shown.

[0017] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the sulfate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the sulfate crystal form has characteristic diffraction peaks at the following 2θ angles: 7.0° ± 0.2°, 14.2° ± 0.2°, 20.3° ± 0.2°, 21.0° ± 0.2°, 22.2° ± 0.2°, 23.7° ± 0.2°, 24.9° ± 0.2°.

[0018] Preferably, the X-ray powder diffraction pattern of the sulfate crystal form has characteristic diffraction peaks at the following 2θ angles: 7.0° ± 0.2°, 14.2° ± 0.2°, 20.3° ± 0.2°, 21.0° ± 0.2°, 22.2° ± 0.2°, 22.5° ± 0.2°, 23.7° ± 0.2°, 24.9° ± 0.2°, 26.0° ± 0.2°.

[0019] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the sulfate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 9.9° ± 0.2°, 18.0° ± 0.2°, 19.0° ± 0.2°, 22.5° ± 0.2°, 24.5° ± 0.2°, 25.5° ± 0.2°, 26.0° ± 0.2°, 27.7° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the sulfate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 9.9° ± 0.2°, 15.8° ± 0.2°, 18.0° ± 0.2°, 19.0° ± 0.2°, 20.0° ± 0.2°, 21.9° ± 0.2°, 24.5° ± 0.2°, 25.5° ± 0.2°, 27.7° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the sulfate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 9.9° ± 0.2°, 18.0° ± 0.2°, 19.0° ± 0.2°.

[0020] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the sulfate crystal form has characteristic diffraction peaks at the following 2θ angles: 7.0° ± 0.2°, 9.9° ± 0.2°, 14.2° ± 0.2°, 18.0° ± 0.2°, 19.0° ± 0.2°, 20.3° ± 0.2°, 21.0° ± 0.2°, 22.2° ± 0.2°, 22.5° ± 0.2°, 23.7° ± 0.2°, 24.9° ± 0.2°, 26.0° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the sulfate crystal form has characteristic diffraction peaks at the following 2θ angles: 7.0° ± 0.2°, 9.9° ± 0.2°, 14.2° ± 0.2°, 15.8° ± 0.2°, 18.0° ± 0.2°, 19.0° ± 0.2°, 20.0° ± 0.2°, 20.3° ± 0.2°, 21.0° ± 0.2°, 21.9° ± 0.2°, 22.2° ± 0.2°, 22.5° ± 0.2°, 23.7° ± 0.2°, 24.5° ± 0.2°, 24.9° ± 0.2°, 25.5° ± 0.2°, 26.0° ± 0.2°, 27.7° ± 0.2°.

[0021] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the sulfate crystal form is shown in Table 11, where the error range of 2θ of each characteristic diffraction peak is ±0.2°. According to an embodiment of the present invention, the sulfate crystal form has an X-ray powder diffraction pattern substantially as Figure 31 shown. According to an embodiment of the present invention, the differential scanning calorimetry diagram of the sulfate crystal form is as Figure 32 shown.

[0022] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the tartrate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the tartrate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.9° ± 0.2°, 10.1° ± 0.2°, 14.2° ± 0.2°, 14.7° ± 0.2°, 18.4° ± 0.2°, 18.8° ± 0.2°, 19.9° ± 0.2°, 20.7° ± 0.2°, 21.9° ± 0.2°, 22.5° ± 0.2°, 23.9° ± 0.2°.

[0023] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the tartrate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 9.9° ± 0.2°, 18.6° ± 0.2°, 24.7° ± 0.2°, 25.8° ± 0.2°, 30.0° ± 0.2°, 30.5° ± 0.2°.

[0024] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the tartrate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.9° ± 0.2°, 14.2° ± 0.2°, 14.7° ± 0.2°, 18.4° ± 0.2°, 19.9° ± 0.2°, 20.7° ± 0.2°, 23.9° ± 0.2°, 24.7° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the tartrate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 9.9° ± 0.2°, 10.1° ± 0.2°, 18.6° ± 0.2°, 18.8° ± 0.2°, 21.9° ± 0.2°, 22.5° ± 0.2°, 25.8° ± 0.2°.

[0025] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the tartrate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.9° ± 0.2°, 9.9° ± 0.2°, 10.1° ± 0.2°, 14.2° ± 0.2°, 14.7° ± 0.2°, 18.4° ± 0.2°, 18.6° ± 0.2°, 18.8° ± 0.2°, 19.9° ± 0.2°, 20.7° ± 0.2°, 21.9° ± 0.2°, 22.5° ± 0.2°, 23.9° ± 0.2°, 24.7° ± 0.2°, 25.8° ± 0.2°, 30.0° ± 0.2°, 30.5° ± 0.2°.

[0026] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the tartrate crystal form are shown in Table 2. According to an embodiment of the present invention, the tartrate crystal form has an X-ray powder diffraction pattern substantially as Figure 4 shown. According to an embodiment of the present invention, the differential scanning calorimetry curve of the tartrate crystal form contains an endothermic peak at 212.2°C ± 3°C ( Figure 5 ). According to an embodiment of the present invention, the differential scanning calorimetry curve of the tartrate crystal form is as Figure 5 shown.

[0027] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the malonate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the malonate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.9° ± 0.2°, 13.3° ± 0.2°, 13.8° ± 0.2°, 14.7° ± 0.2°, 19.6° ± 0.2°, 25.2° ± 0.2°, 25.4° ± 0.2°.

[0028] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the malonate crystal form further comprises one, two or more characteristic diffraction peaks at the following 2θ angles: 9.8° ± 0.2°, 12.7° ± 0.2°, 18.3° ± 0.2°, 18.9° ± 0.2°, 26.8° ± 0.2°.

[0029] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the malonate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.9° ± 0.2°, 13.3° ± 0.2°, 13.8° ± 0.2°, 19.6° ± 0.2°, 25.2° ± 0.2°, 25.4° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the malonate crystal form further comprises one, two or more characteristic diffraction peaks at the following 2θ angles: 9.8° ± 0.2°, 12.7° ± 0.2°, 14.7° ± 0.2°, 18.3° ± 0.2°, 18.9° ± 0.2°, 26.8° ± 0.2°.

[0030] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the malonate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.9° ± 0.2°, 9.8° ± 0.2°, 12.7° ± 0.2°, 13.3° ± 0.2°, 13.8° ± 0.2°, 14.7° ± 0.2°, 18.3° ± 0.2°, 18.9° ± 0.2°, 19.6° ± 0.2°, 25.2° ± 0.2°, 25.4° ± 0.2°, 26.8° ± 0.2°.

[0031] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the malonate crystal form are shown in Table 3. According to an embodiment of the present invention, the malonate crystal form has an X-ray powder diffraction pattern substantially as Figure 7 shown. According to an embodiment of the present invention, the differential scanning calorimetry diagram of the malonate crystal form is as Figure 8 shown.

[0032] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the 1,2-ethanedisulfonate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.6° ± 0.2°, 12.0° ± 0.2°, 15.8° ± 0.2°, 17.1° ± 0.2°, 19.8° ± 0.2°, 20.1° ± 0.2°, 23.0° ± 0.2°, 23.5° ± 0.2°.

[0033] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate crystal form further comprises one, two or more characteristic diffraction peaks at the following 2θ angles: 13.2° ± 0.2°, 13.4° ± 0.2°, 16.0° ± 0.2°, 18.2° ± 0.2°, 20.3° ± 0.2°, 23.9° ± 0.2°.

[0034] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.6° ± 0.2°, 12.0° ± 0.2°, 17.1° ± 0.2°, 19.8° ± 0.2°, 20.1° ± 0.2°, 23.5° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate crystal form further comprises one, two or more characteristic diffraction peaks at the following 2θ angles: 13.2° ± 0.2°, 13.4° ± 0.2°, 15.8° ± 0.2°, 16.0° ± 0.2°, 18.0° ± 0.2°, 18.2° ± 0.2°, 20.3° ± 0.2°, 23.0° ± 0.2°, 23.9° ± 0.2°, 26.1° ± 0.2°, 26.4° ± 0.2°, 26.9° ± 0.2°.

[0035] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.6° ± 0.2°, 12.0° ± 0.2°, 13.2° ± 0.2°, 13.4° ± 0.2°, 15.8° ± 0.2°, 16.0° ± 0.2°, 17.1° ± 0.2°, 18.2° ± 0.2°, 19.8° ± 0.2°, 20.1° ± 0.2°, 20.3° ± 0.2°, 23.0° ± 0.2°, 23.5° ± 0.2°, 23.9° ± 0.2°.

[0036] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the 1,2-ethanedisulfonate crystal form is shown in Table 4. According to an embodiment of the present invention, the 1,2-ethanedisulfonate crystal form has an X-ray powder diffraction pattern substantially as Figure 10 shown. According to an embodiment of the present invention, the differential scanning calorimetry curve of the 1,2-ethanedisulfonate crystal form contains an endothermic peak at 279°C ± 3°C ( Figure 11 ). According to an embodiment of the present invention, the differential scanning calorimetry curve of the 1,2-ethanedisulfonate crystal form is as Figure 11 shown.

[0037] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the p-toluenesulfonate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the p-toluenesulfonate crystal form has characteristic diffraction peaks at the following 2θ angles: 7.4° ± 0.2°, 9.7° ± 0.2°, 11.1° ± 0.2°, 13.8° ± 0.2°, 19.3° ± 0.2°, 24.0° ± 0.2°, 24.4° ± 0.2°, 24.9° ± 0.2°, 26.6° ± 0.2°.

[0038] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the p-toluenesulfonate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 12.7° ± 0.2°, 21.0° ± 0.2°, 21.5° ± 0.2°, 21.9° ± 0.2°, 22.1° ± 0.2°, 22.4° ± 0.2°, 22.7° ± 0.2°, 26.0° ± 0.2°, 27.9° ± 0.2°.

[0039] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the p-toluenesulfonate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 4.0° ± 0.2°, 12.7° ± 0.2°, 13.0° ± 0.2°, 15.7° ± 0.2°, 17.0° ± 0.2°, 18.0° ± 0.2°, 20.0° ± 0.2°, 20.4° ± 0.2°, 21.0° ± 0.2°, 21.5° ± 0.2°, 21.9° ± 0.2°, 22.1° ± 0.2°, 22.4° ± 0.2°, 22.7° ± 0.2°, 25.3° ± 0.2°, 26.0° ± 0.2°, 27.9° ± 0.2°.

[0040] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the p-toluenesulfonate crystal form has characteristic diffraction peaks at the following 2θ angles: 7.4° ± 0.2°, 9.7° ± 0.2°, 11.1° ± 0.2°, 12.7° ± 0.2°, 13.8° ± 0.2°, 19.3° ± 0.2°, 21.0° ± 0.2°, 21.5° ± 0.2°, 21.9° ± 0.2°, 22.1° ± 0.2°, 22.4° ± 0.2°, 22.7° ± 0.2°, 24.0° ± 0.2°, 24.4° ± 0.2°, 24.9° ± 0.2°, 26.0° ± 0.2°, 26.6° ± 0.2°, 27.9° ± 0.2°.

[0041] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the p-toluenesulfonate crystal form is shown in Table 5. According to an embodiment of the present invention, the p-toluenesulfonate crystal form has substantially asFigure 13 The X-ray powder diffraction pattern shown. According to an embodiment of the present invention, the differential scanning calorimetry pattern of the p-toluenesulfonate crystal form is as Figure 14 shown.

[0042] According to an embodiment of the present invention, the polymorph of the salt of the compound shown by formula (I) is the hydrochloride crystal form of the compound shown by formula (I); preferably, the X-ray powder diffraction pattern of the hydrochloride crystal form has characteristic diffraction peaks at the following 2θ angles: 10.4° ± 0.2°, 17.1° ± 0.2°, 20.1° ± 0.2°, 24.4° ± 0.2°, 24.6° ± 0.2°, 26.7° ± 0.2°; preferably, the X-ray powder diffraction pattern of the hydrochloride crystal form has characteristic diffraction peaks at the following 2θ angles: 10.4° ± 0.2°, 17.1° ± 0.2°, 20.1° ± 0.2°, 20.6° ± 0.2°, 23.0° ± 0.2°, 24.4° ± 0.2°, 24.6° ± 0.2°, 26.7° ± 0.2°.

[0043] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrochloride crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 10.9° ± 0.2°, 15.2° ± 0.2°, 15.6° ± 0.2°, 17.6° ± 0.2°, 19.4° ± 0.2°, 20.8° ± 0.2°, 21.8° ± 0.2°, 22.1° ± 0.2°, 25.4° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrochloride crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 10.9° ± 0.2°, 17.6° ± 0.2°, 19.4° ± 0.2°, 25.4° ± 0.2°.

[0044] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrochloride crystal form has characteristic diffraction peaks at the following 2θ angles: 10.4° ± 0.2°, 20.1° ± 0.2°, 23.0° ± 0.2°, 24.4° ± 0.2°, 24.6° ± 0.2°, 26.7° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrochloride crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 10.9° ± 0.2°, 17.1° ± 0.2°, 19.4° ± 0.2°, 20.6° ± 0.2°, 20.8° ± 0.2°, 21.8° ± 0.2°, 22.0° ± 0.2°, 25.4° ± 0.2°.

[0045] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrochloride crystal form has characteristic diffraction peaks at the following 2θ angles: 10.4° ± 0.2°, 10.9° ± 0.2°, 17.1° ± 0.2°, 17.6° ± 0.2°, 19.4° ± 0.2°, 20.1° ± 0.2°, 20.6° ± 0.2°, 23.0° ± 0.2°, 24.4° ± 0.2°, 24.6° ± 0.2°, 25.4° ± 0.2°, 26.7° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrochloride crystal form has characteristic diffraction peaks at the following 2θ angles: 10.4° ± 0.2°, 10.9° ± 0.2°, 15.2° ± 0.2°, 15.6° ± 0.2°, 17.1° ± 0.2°, 17.6° ± 0.2°, 19.4° ± 0.2°, 20.1° ± 0.2°, 20.6° ± 0.2°, 20.8° ± 0.2°, 21.8° ± 0.2°, 22.1° ± 0.2°, 23.0° ± 0.2°, 24.4° ± 0.2°, 24.6° ± 0.2°, 25.4° ± 0.2°, 26.7° ± 0.2°.

[0046] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the hydrochloride crystal form is shown in Table 6. According to an embodiment of the present invention, the hydrochloride crystal form has an X-ray powder diffraction pattern substantially as Figure 16 shown. According to an embodiment of the present invention, the differential scanning calorimetry curve of the hydrochloride crystal form contains an endothermic peak at 215°C ± 3°C ( Figure 17 ). According to an embodiment of the present invention, the differential scanning calorimetry curve of the hydrochloride crystal form is as Figure 17 shown.

[0047] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the mesylate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the mesylate crystal form has characteristic diffraction peaks at the following 2θ angles: 12.5° ± 0.2°, 16.9° ± 0.2°, 18.0° ± 0.2°, 18.7° ± 0.2°, 19.8° ± 0.2°, 23.1° ± 0.2°, 23.4° ± 0.2°, 24.0° ± 0.2°.

[0048] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the mesylate crystal form further comprises one, two or more characteristic diffraction peaks at the following 2θ angles: 6.4° ± 0.2°, 6.6° ± 0.2°, 11.8° ± 0.2°, 16.1° ± 0.2°, 17.5° ± 0.2°, 18.9° ± 0.2°, 20.0° ± 0.2°, 20.9° ± 0.2°, 22.7° ± 0.2°, 24.4° ± 0.2°, 25.2° ± 0.2°, 26.0° ± 0.2°.

[0049] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the mesylate crystal form has characteristic diffraction peaks at the following 2θ angles: 12.5° ± 0.2°, 16.9° ± 0.2°, 18.0° ± 0.2°, 18.7° ± 0.2°, 19.8° ± 0.2°, 23.1° ± 0.2°, 23.4° ± 0.2°, 24.0° ± 0.2°, 25.2° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the mesylate crystal form further comprises one, two or more characteristic diffraction peaks at the following 2θ angles: 6.4° ± 0.2°, 6.6° ± 0.2°, 11.8° ± 0.2°, 13.5° ± 0.2°, 16.1° ± 0.2°, 16.3° ± 0.2°, 17.5° ± 0.2°, 18.9° ± 0.2°, 20.0° ± 0.2°, 20.6° ± 0.2°, 20.9° ± 0.2°, 22.7° ± 0.2°, 24.4° ± 0.2°, 26.0° ± 0.2°.

[0050] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the mesylate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.4° ± 0.2°, 6.6° ± 0.2°, 11.8° ± 0.2°, 12.5° ± 0.2°, 16.1° ± 0.2°, 16.9° ± 0.2°, 17.5° ± 0.2°, 18.0° ± 0.2°, 18.7° ± 0.2°, 18.9° ± 0.2°, 19.8° ± 0.2°, 20.0° ± 0.2°, 20.9° ± 0.2°, 22.7° ± 0.2°, 23.1° ± 0.2°, 23.4° ± 0.2°, 24.0° ± 0.2°, 24.4° ± 0.2°, 25.2° ± 0.2°, 26.0° ± 0.2°.

[0051] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the mesylate crystal form is shown in Table 7. According to an embodiment of the present invention, the mesylate crystal form has an X-ray powder diffraction pattern substantially as Figure 19 shown. According to an embodiment of the present invention, the differential scanning calorimetry diagram of the mesylate crystal form is as Figure 20as shown

[0052] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the hydrobromide crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the hydrobromide crystal form has characteristic diffraction peaks at the following 2θ angles: 10.4° ± 0.2°, 15.5° ± 0.2°, 20.1° ± 0.2°, 20.5° ± 0.2°, 23.2° ± 0.2°, 24.3° ± 0.2°, 24.5° ± 0.2°, 26.5° ± 0.2°.

[0053] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrobromide crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 6.8° ± 0.2°, 14.7° ± 0.2°, 17.0° ± 0.2°, 19.4° ± 0.2°, 19.9° ± 0.2°, 21.0° ± 0.2°, 22.3° ± 0.2°, 23.7° ± 0.2°, 25.4° ± 0.2°, 27.3° ± 0.2°, 33.7° ± 0.2°.

[0054] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrobromide crystal form has characteristic diffraction peaks at the following 2θ angles: 20.1° ± 0.2°, 20.5° ± 0.2°, 23.2° ± 0.2°, 24.3° ± 0.2°, 24.5° ± 0.2°, 25.4° ± 0.2°, 26.5° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrobromide crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 6.8° ± 0.2°, 10.4° ± 0.2°, 14.7° ± 0.2°, 15.5° ± 0.2°, 17.0° ± 0.2°, 19.4° ± 0.2°, 19.9° ± 0.2°, 21.0° ± 0.2°, 22.3° ± 0.2°, 23.7° ± 0.2°, 27.3° ± 0.2°, 33.7° ± 0.2°.

[0055] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrobromide crystal form has characteristic diffraction peaks at the following 2θ angles: 6.8°±0.2°, 10.4°±0.2°, 14.7°±0.2°, 15.5°±0.2°, 17.0°±0.2°, 19.4°±0.2°, 19.9°±0.2°, 20.1°±0.2°, 20.5°±0.2°, 21.0°±0.2°, 22.3°±0.2°, 23.2°±0.2°, 23.7°±0.2°, 24.3°±0.2°, 24.5°±0.2°, 25.4°±0.2°, 26.5°±0.2°, 27.3°±0.2°, 33.7°±0.2°.

[0056] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the hydrobromide crystal form are shown in Table 8. According to an embodiment of the present invention, the hydrobromide crystal form has an X-ray powder diffraction pattern substantially as Figure 22 shown. According to an embodiment of the present invention, the differential scanning calorimetry diagram of the hydrobromide is as Figure 23 shown.

[0057] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the malate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the malate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.8°±0.2°, 10.2°±0.2°, 14.6°±0.2°, 18.3°±0.2°, 19.7°±0.2°, 23.1°±0.2°, 23.7°±0.2°, 25.2°±0.2°.

[0058] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the malate crystal form further includes characteristic diffraction peaks at one, two or more of the following 2θ angles: 10.0°±0.2°, 18.8°±0.2°, 19.1°±0.2°, 20.4°±0.2°, 21.7°±0.2°, 25.6°±0.2°.

[0059] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the malate crystal form has characteristic diffraction peaks at the following 2θ angles: 10.2° ± 0.2°, 14.6° ± 0.2°, 18.3° ± 0.2°, 23.1° ± 0.2°, 23.7° ± 0.2°, 25.2° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the malate crystal form further includes characteristic diffraction peaks at one, two, or more of the following 2θ angles: 6.8° ± 0.2°, 10.0° ± 0.2°, 18.8° ± 0.2°, 19.1° ± 0.2°, 19.7° ± 0.2°, 20.4° ± 0.2°, 21.7° ± 0.2°, 25.6° ± 0.2°.

[0060] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the malate crystal form has characteristic diffraction peaks at the following 2θ angles: 6.8° ± 0.2°, 10.0° ± 0.2°, 10.2° ± 0.2°, 14.6° ± 0.2°, 18.3° ± 0.2°, 18.8° ± 0.2°, 19.1° ± 0.2°, 19.7° ± 0.2°, 20.4° ± 0.2°, 21.7° ± 0.2°, 23.1° ± 0.2°, 23.7° ± 0.2°, 25.2° ± 0.2°, 25.6° ± 0.2°.

[0061] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the malate crystal form is shown in Table 9. According to an embodiment of the present invention, the malate crystal form has an X-ray powder diffraction pattern substantially as Figure 25 shown. According to an embodiment of the present invention, the differential scanning calorimetry chart of the malate crystal form contains an endothermic peak at 206°C ± 3°C ( Figure 26 ). According to an embodiment of the present invention, the differential scanning calorimetry chart of the malate crystal form is as Figure 26 shown.

[0062] According to an embodiment of the present invention, the polymorph of the salt of the compound represented by formula (I) is the fumarate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the fumarate crystal form has characteristic diffraction peaks at the following 2θ angles:: 9.4° ± 0.2°, 13.1° ± 0.2°, 14.1° ± 0.2°, 17.7° ± 0.2°, 21.6° ± 0.2°, 25.6° ± 0.2°.

[0063] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the fumarate crystal form further comprises one, two or more characteristic diffraction peaks at the following 2θ angles: 7.0° ± 0.2°, 11.2° ± 0.2°, 12.5° ± 0.2°, 13.7° ± 0.2°, 18.7° ± 0.2°, 19.4° ± 0.2°, 20.3° ± 0.2°, 21.9° ± 0.2°, 22.5° ± 0.2°, 25.3° ± 0.2°.

[0064] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the fumarate crystal form has characteristic diffraction peaks at the following 2θ angles: 9.4° ± 0.2°, 13.1° ± 0.2°, 17.7° ± 0.2°, 21.6° ± 0.2°, 25.6° ± 0.2°. According to an embodiment of the present invention, the X-ray powder diffraction pattern of the fumarate crystal form further comprises one, two or more characteristic diffraction peaks at the following 2θ angles: 7.0° ± 0.2°, 11.2° ± 0.2°, 12.5° ± 0.2°, 13.7° ± 0.2°, 14.1° ± 0.2°, 19.4° ± 0.2°, 20.3° ± 0.2°, 22.5° ± 0.2°.

[0065] According to an embodiment of the present invention, the X-ray powder diffraction pattern of the fumarate crystal form has characteristic diffraction peaks at the following 2θ angles: 7.0° ± 0.2°, 9.4° ± 0.2°, 11.2° ± 0.2°, 12.5° ± 0.2°, 13.1° ± 0.2°, 13.7° ± 0.2°, 14.1° ± 0.2°, 17.7° ± 0.2°, 18.7° ± 0.2°, 19.4° ± 0.2°, 20.3° ± 0.2°, 21.6° ± 0.2°, 21.9° ± 0.2°, 22.5° ± 0.2°, 25.3° ± 0.2°, 25.6° ± 0.2°.

[0066] According to an embodiment of the present invention, the X-ray powder diffraction pattern analysis data of the fumarate crystal form is shown in Table 10. According to an embodiment of the present invention, the fumarate crystal form has an X-ray powder diffraction pattern substantially as Figure 28 shown. According to an embodiment of the present invention, the differential scanning calorimetry curve of the fumarate crystal form contains an endothermic peak at 248°C ± 3°C ( Figure 29 ). According to an embodiment of the present invention, the differential scanning calorimetry curve of the fumarate crystal form is as Figure 29 shown.

[0067] The present invention also provides a pharmaceutical composition, which comprises a salt or a polymorph of the compound shown in the above formula (I), and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant or a combination thereof.

[0068] According to an embodiment of the present invention, the pharmaceutical composition is used for preventing and / or treating diseases caused by excessive gastric acid secretion; preferably, the disease is a gastrointestinal inflammatory disease or a gastric acid-related disease.

[0069] According to an embodiment of the present invention, the gastrointestinal inflammatory disease or the gastric acid-related disease includes but is not limited to peptic ulcer, gastric and duodenal ulcer, non-steroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD), and non-invasive reflux disease (NERD).

[0070] The present invention also provides the use of a salt or a polymorph of the compound represented by the above formula (I) and the pharmaceutical composition in the preparation of a drug for preventing and / or treating diseases caused by excessive gastric acid secretion; preferably, the disease is a gastrointestinal inflammatory disease or a gastric acid-related disease.

[0071] According to an embodiment of the present invention, the gastrointestinal inflammatory disease or the gastric acid-related disease includes but is not limited to peptic ulcer, gastric and duodenal ulcer, non-steroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD), and non-invasive reflux disease (NERD).

[0072] The present invention also provides a method for preventing and / or treating diseases caused by excessive gastric acid secretion, the method comprising administering to a patient an effective amount of a salt or a polymorph of the compound represented by the above formula (I) or the above pharmaceutical composition; preferably, the disease is a gastrointestinal inflammatory disease or a gastric acid-related disease.

[0073] According to an embodiment of the present invention, the gastrointestinal inflammatory disease or the gastric acid-related disease includes but is not limited to peptic ulcer, gastric and duodenal ulcer, non-steroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD), and non-invasive reflux disease (NERD).

[0074] The present invention also provides a method for preparing a salt or a polymorph of the compound represented by the above formula (I);

[0075] The method for preparing the salt includes: mixing the compound represented by formula (I) with a salt to obtain the salt of the compound represented by formula (I);

[0076] The method for preparing the polymorph of the salt includes: mixing the compound represented by formula (I) with a salt and crystallizing to obtain the polymorph of the salt of the compound represented by formula (I).

[0077] There is no particular limitation on the solvent used in the preparation method of the salt or its polymorph of the present invention, and any solvent that can dissolve the starting material to a certain extent without affecting its properties is included in the present invention. In addition, many similar modifications, equivalent substitutions, or solvents, solvent combinations, and different proportions of solvent combinations equivalent to those described in the present invention are regarded as within the scope of the present invention. The preferred solvents used in each reaction step are given in the present invention.

[0078] According to an embodiment of the present invention, the preparation method of the phosphate polymorph is as follows: Mix the solution of the compound shown in formula (I) with a phosphoric acid solution, perform solid-liquid separation to obtain a solid, and dry it to obtain the phosphate polymorph. According to an embodiment of the present invention, the molar ratio of the compound shown in formula (I) to phosphoric acid is 1:0.9 to 1:1.1, for example, 1:1.1. According to an embodiment of the present invention, the drying method is vacuum drying, for example, vacuum drying at room temperature; the drying time is preferably overnight. The solid-liquid separation is filtration, centrifugation, etc.

[0079] According to an embodiment of the present invention, the solution of the compound shown in formula (I) is prepared as follows: Dissolve the compound shown in formula (I) in an alcohol solvent to form a solution of the compound shown in formula (I); preferably, the alcohol solvent is methanol, ethanol, n-propanol, isopropanol, n-butanol, etc.; preferably, the concentration of the solution of the compound shown in formula (I) is 0.01 mol / L - 2.0 mol / L, for example, 0.06 mol / L. According to an embodiment of the present invention, the phosphoric acid solution is prepared as follows: Dissolve phosphoric acid in an alcohol solvent to form a phosphoric acid solution; preferably, the alcohol solvent is methanol, ethanol, n-butanol, etc.; preferably, the concentration of the phosphoric acid solution is 0.1 mol / L - 5 mol / L, for example, 1 mol / L. According to an embodiment of the present invention, the specific preparation method is: Mix the solution of the compound shown in formula (I) with the phosphoric acid solution, stir for 1 day, centrifuge to obtain a solid, and vacuum dry at room temperature overnight to obtain the phosphate polymorph.

[0080] According to an embodiment of the present invention, the preparation method of the hydrochloride crystal form is as follows: The compound shown in formula (I) and hydrochloric acid are added to Solvent-1, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the hydrochloride crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-1 is selected from n-hexane, cyclohexane, and acetone. According to an embodiment of the present invention, the molar ratio of the compound shown in formula (I) to hydrochloric acid is 1:0.9 to 1:1.1, such as 1:1.1. According to an embodiment of the present invention, the ratio of the compound shown in formula (I) to Solvent-1 is: 0.01 mol - 0.20 mol: 1 mL, such as 0.06 mol: 1 mL. According to an embodiment of the present invention, the specific preparation method is: The compound shown in formula (I) and hydrochloric acid are added to Solvent-1, stirred at room temperature for 2 days, centrifuged to obtain a solid, and dried to obtain the hydrochloride crystal form.

[0081] According to an embodiment of the present invention, the preparation method of the sulfate crystal form is as follows: The compound shown in formula (I) and sulfuric acid are added to Solvent-2, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the sulfate crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-2 is selected from alcohol solvents, such as isopropyl alcohol, cyclohexane. According to an embodiment of the present invention, the molar ratio of the compound shown in formula (I) to sulfuric acid is 1:0.9 to 1:1.1, such as 1:1.1. According to an embodiment of the present invention, the ratio of the compound shown in formula (I) to Solvent-2 is: 0.01 mol - 0.20 mol: 1 mL, such as 0.06 mol: 1 mL. According to an embodiment of the present invention, the specific preparation method is: The compound shown in formula (I) and sulfuric acid are added to Solvent-2, stirred at room temperature for 2 days, centrifuged to obtain a solid, and dried to obtain the sulfate crystal form.

[0082] According to an embodiment of the present invention, the preparation method of the tartrate crystal form is as follows: The compound shown in formula (I) and tartaric acid are added to Solvent-3, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the tartrate crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-3 is acetone.

[0083] According to an embodiment of the present invention, the preparation method of the 1,2-ethanedisulfonate crystal form is as follows: The compound shown in formula (I) and 1,2-ethanedisulfonic acid are added to Solvent-4, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the 1,2-ethanedisulfonate crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-4 is isopropanol.

[0084] According to an embodiment of the present invention, the preparation method of the p-toluenesulfonic acid crystal form is as follows: The compound shown in formula (I) and p-toluenesulfonic acid are added to Solvent-5, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the p-toluenesulfonate crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-5 is n-heptane.

[0085] According to an embodiment of the present invention, the preparation method of the methanesulfonic acid crystal form is as follows: The compound shown in formula (I) and methanesulfonic acid are added to Solvent-6, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the methanesulfonate crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-6 is n-heptane.

[0086] According to an embodiment of the present invention, the preparation method of the hydrobromic acid crystal form is as follows: The compound shown in formula (I) and hydrobromic acid are added to Solvent-7, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the hydrobromic acid crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-7 is n-hexane.

[0087] According to an embodiment of the present invention, the preparation method of the malic acid crystal form is as follows: The compound shown in formula (I) and malic acid are added to Solvent-8, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the malic acid crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-8 is acetone.

[0088] According to an embodiment of the present invention, the preparation method of the fumaric acid crystal form is as follows: The compound shown in formula (I) and fumaric acid are added to Solvent-9, stirred, and solid-liquid separation is carried out to obtain a solid, which is dried to obtain the fumaric acid crystal form. According to an embodiment of the present invention, the drying method is vacuum drying, such as vacuum drying at room temperature. The solid-liquid separation is filtration, centrifugation, etc. According to an embodiment of the present invention, Solvent-9 is n-heptane.

[0089] Beneficial effects:

[0090] The present invention provides a salt or a polymorph thereof of a compound represented by formula (I), and the salt or its polymorph has excellent drug-likeness, such as good solubility, light stability, bioavailability, etc. Description of the Drawings

[0091] Figure 1 It is an X-ray powder diffraction (XRPD) pattern of the phosphate salt of the compound represented by formula (I).

[0092] Figure 2 It is a differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) pattern of the phosphate salt of the compound represented by formula (I).

[0093] Figure 3 It is a nuclear magnetic resonance hydrogen spectrum ( 1 1H NMR) pattern of the phosphate salt of the compound represented by formula (I).

[0094] Figure 4 It is an X-ray powder diffraction (XRPD) pattern of the tartrate salt of the compound represented by formula (I).

[0095] Figure 5 It is a differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) pattern of the tartrate salt of the compound represented by formula (I).

[0096] Figure 6 It is a nuclear magnetic resonance hydrogen spectrum ( 1 1H NMR) pattern of the tartrate salt of the compound represented by formula (I).

[0097] Figure 7 It is an X-ray powder diffraction (XRPD) pattern of the malonate salt of the compound represented by formula (I).

[0098] Figure 8 It is a differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) pattern of the malonate salt of the compound represented by formula (I).

[0099] Figure 9 It is a nuclear magnetic resonance hydrogen spectrum ( 1 1H NMR) pattern of the malonate salt of the compound represented by formula (I).

[0100] Figure 10 It is an X-ray powder diffraction (XRPD) pattern of the 1,2-ethanedisulfonate salt of the compound represented by formula (I).

[0101] Figure 11 It is a differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) pattern of the 1,2-ethanedisulfonate salt of the compound represented by formula (I).

[0102] Figure 121H NMR spectrum of the 1,2-ethanedisulfonate salt of the compound of formula (I). 1 H NMR

[0103] Figure 13 X-ray powder diffraction (XRPD) pattern of the p-toluenesulfonate salt of the compound of formula (I).

[0104] Figure 14 Differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) curve of the p-toluenesulfonate salt of the compound of formula (I).

[0105] Figure 15 1H NMR spectrum of the p-toluenesulfonate salt of the compound of formula (I). 1 H NMR

[0106] Figure 16 X-ray powder diffraction (XRPD) pattern of the hydrochloride salt of the compound of formula (I).

[0107] Figure 17 Differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) curve of the hydrochloride salt of the compound of formula (I).

[0108] Figure 18 1H NMR spectrum of the hydrochloride salt of the compound of formula (I). 1 H NMR

[0109] Figure 19 X-ray powder diffraction (XRPD) pattern of the methanesulfonate salt of the compound of formula (I).

[0110] Figure 20 Differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) curve of the methanesulfonate salt of the compound of formula (I).

[0111] Figure 21 1H NMR spectrum of the methanesulfonate salt of the compound of formula (I). 1 H NMR

[0112] Figure 22 X-ray powder diffraction (XRPD) pattern of the hydrobromide salt of the compound of formula (I).

[0113] Figure 23 Differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) curve of the hydrobromide salt of the compound of formula (I).

[0114] Figure 24 1H NMR spectrum of the hydrobromide salt of the compound of formula (I). 1 H NMR

[0115] Figure 25 The X-ray powder diffraction (XRPD) pattern of the malate salt of the compound represented by formula (I).

[0116] Figure 26 The differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) pattern of the malate salt of the compound represented by formula (I).

[0117] Figure 27 The nuclear magnetic resonance hydrogen spectrum ( 1 1H NMR) pattern of the malate salt of the compound represented by formula (I).

[0118] Figure 28 The X-ray powder diffraction (XRPD) pattern of the fumarate salt of the compound represented by formula (I).

[0119] Figure 29 The differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) pattern of the fumarate salt of the compound represented by formula (I).

[0120] Figure 30 The nuclear magnetic resonance hydrogen spectrum ( 1 1H NMR) pattern of the fumarate salt of the compound represented by formula (I).

[0121] Figure 31 The X-ray powder diffraction (XRPD) pattern of the sulfate salt of the compound represented by formula (I).

[0122] Figure 32 The differential scanning calorimetry / thermogravimetric analysis (DSC / TGA) pattern of the sulfate salt of the compound represented by formula (I).

[0123] Figure 33 The nuclear magnetic resonance hydrogen spectrum ( 1 1H NMR) pattern of the sulfate salt of the compound represented by formula (I). Detailed implementation manners

[0124] In the following examples of the present invention, the experimental methods without specific conditions noted are usually carried out under conventional conditions or according to the conditions recommended by the manufacturers. All common chemical reagents used in the examples are commercially available products.

[0125] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the description of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0126] The terms "comprise" and "include" in the present invention and any variations thereof are intended to cover non-exclusive inclusion. For example, a process, method, apparatus, product or device that includes a series of steps is not limited to the listed steps or modules, but may optionally further include steps not listed, or may optionally further include other steps inherent to these processes, methods, products or devices.

[0127] As used in the present invention, "a plurality of" means two or more. "And / or" describes the relationship between associated objects and indicates that there can be three relationships. For example, A and / or B can represent: A exists alone, A and B exist simultaneously, and B exists alone. The character " / " generally indicates that the associated objects before and after are in an "or" relationship.

[0128] The present invention will be further described in detail below in conjunction with specific embodiments.

[0129] The compound shown in formula (I) is commonly named Zastaprazan, and its CAS number is 2133852-18-1.

[0130] Example 1

[0131] Preparation method of phosphate: Weigh 218 mg of the compound shown in formula (I) and add it to 10.0 mL of n-propanol. Then add 660 μL of phosphoric acid ethanol solution (1 mol / L). After stirring for 1 day, centrifuge the suspension, and dry the solid under vacuum at room temperature overnight. The obtained solid is a monophosphate crystal form.

[0132] The X-ray powder diffraction data of the phosphate obtained in this example is shown in Table 1, and its XRPD pattern is as Figure 1 shown.

[0133] Table 1

[0134]

[0135] The DSC / TGA of the phosphate is as Figure 2 shown. An endothermic peak appears in the DSC when heated to around 206.9 °C, and there is basically no weight loss in the TGA when heated to 150 °C. The 1 1H NMR of the phosphate is as Figure 3 shown.

[0136] Example 2

[0137] Preparation method of tartrate: Weigh 21.9 mg of the compound shown in formula (I) and 4.8 mg of tartaric acid respectively, add them to 1 mL of acetone, stir at room temperature for 2 days, centrifuge the suspension, and dry the solid under vacuum at room temperature. The obtained solid is the tartrate.

[0138] The X-ray powder diffraction data of the tartrate obtained in this example are shown in Table 2, and its XRPD pattern is as shown in Figure 4 shown.

[0139] Table 2

[0140]

[0141]

[0142] The DSC / TGA of the tartrate is as shown in Figure 5 shown. There is an endothermic peak in the DSC when heated to around 212.2 °C, and there is basically no weight loss in the TGA when heated to 150 °C. The 1 1H NMR of the tartrate is as shown in Figure 6 shown.

[0143] Example 3

[0144] Preparation method of malonate: Weigh 21.2 mg of the compound shown in formula (I) and 7.2 mg of malonic acid respectively, add them to 1 mL of n-propanol, stir at room temperature for 2 days, centrifuge the suspension, and vacuum dry the solid at room temperature. The obtained solid is malonate.

[0145] The X-ray powder diffraction data of the malonate obtained in this example are shown in Table 3, and its XRPD pattern is as shown in Figure 7 shown.

[0146] Table 3

[0147]

[0148] The DSC / TGA of the malonate is as shown in Figure 8 shown. There is an endothermic peak in the DSC when heated to around 82 °C, there is a broad endothermic signal corresponding to the weight loss of the TGA from 145 °C to 180 °C, and there is an endothermic signal at around 196 °C. There is basically no weight loss in the TGA when heated to 100 °C; there is a weight loss of 22.3% from 100 °C to 200 °C. The 1 1H NMR of the malonate is as shown in Figure 9 shown.

[0149] Example 4

[0150] Preparation method of 1,2-ethanedisulfonate: Weigh 21.2 mg of the compound shown in formula (I) and 12.6 mg of 1,2-ethanedisulfonic acid respectively, add them to 1 mL of isopropanol, stir at room temperature for 2 days, centrifuge the suspension, and vacuum dry the solid at room temperature. The obtained solid is 1,2-ethanedisulfonate.

[0151] The X-ray powder diffraction data of the 1,2-ethanedisulfonate obtained in this example are shown in Table 4, and its XRPD pattern is as shown inFigure 10 as shown

[0152] Table 4

[0153]

[0154] The DSC / TGA of 1,2-ethanedisulfonate is as Figure 11 shown. There is an exothermic signal in DSC when heated to around 279 °C; there is basically no weight loss in TGA when heated to 150 °C. The 1 1H NMR of 1,2-ethanedisulfonate is as Figure 12 shown

[0155] Example 5

[0156] Preparation method of p-toluenesulfonate: Weigh 21.4 mg of the compound shown in formula (I) and 12.5 mg of p-toluenesulfonic acid respectively, add them to 1 mL of n-heptane, stir at room temperature for 2 days, centrifuge the suspension, and vacuum dry the solid at room temperature. The obtained solid is p-toluenesulfonate

[0157] The X-ray powder diffraction data of the p-toluenesulfonate obtained in this example is shown in Table 5, and its XRPD pattern is as Figure 13 shown

[0158] Table 5

[0159]

[0160]

[0161] The DSC / TGA of p-toluenesulfonate is as Figure 14 shown. There is a relatively broad endothermic signal corresponding to the weight loss of TGA in DSC when heated from 100 °C to 130 °C, and there is an endothermic signal peak accompanied by exotherm when heated from 200 °C to 260 °C; there is a 0.5% weight loss in TGA when heated to 150 °C. The 1 1H NMR of p-toluenesulfonate is as Figure 15 shown

[0162] Example 6

[0163] Preparation method of hydrochloride: Weigh 21.6 mg of the compound shown in formula (I) and 66 μL of 1 M hydrochloride respectively, add them to 1 mL of n-hexane, stir at room temperature for 2 days, centrifuge the suspension, and vacuum dry the solid at room temperature. The obtained solid is hydrochloride

[0164] The X-ray powder diffraction data of the hydrochloride obtained in this example is shown in Table 6, and its XRPD pattern is as Figure 16 shown

[0165] Table 6

[0166]

[0167] The DSC / TGA of the hydrochloride is as Figure 17 shown. There is an endothermic signal peak in the DSC when heated to 215 °C; there is a weight loss of 0.8% in the TGA when heated to 150 °C. The 1 1H NMR of the hydrochloride is as Figure 18 shown.

[0168] Example 7

[0169] Preparation method of mesylate: Weigh 21.4 mg of the compound shown in formula (I) and 66 μL of 1 M methanesulfonic acid respectively, add them to 1 mL of n-heptane, stir at room temperature for 2 days, centrifuge the suspension, and vacuum dry the solid at room temperature. The obtained solid is mesylate.

[0170] The X-ray powder diffraction data of the mesylate obtained in this example is shown in Table 7, and its XRPD pattern is as Figure 19 shown.

[0171] Table 7

[0172]

[0173] The DSC / TGA of the mesylate is as Figure 20 shown. There is a relatively broad endothermic signal corresponding to the weight loss of the TGA in the DSC from 70 °C to 115 °C, and endothermic signals at about 191 °C and 203 °C; there is a weight loss of 2.5% in the TGA when heated to 100 °C. The 1 1H NMR of the mesylate is as Figure 21 shown.

[0174] Example 8

[0175] Preparation method of hydrobromide: Weigh 21.6 mg of the compound shown in formula (I) and 66 μL of 1 M hydrobromic acid respectively, add them to 1 mL of n-hexane, stir at room temperature for 2 days, centrifuge the suspension, and vacuum dry the solid at room temperature. The obtained solid is hydrobromide.

[0176] The X-ray powder diffraction data of the hydrobromide obtained in this example is shown in Table 8, and its XRPD pattern is as Figure 22 shown.

[0177] Table 8

[0178]

[0179]

[0180] The DSC / TGA of the hydrobromide is as Figure 23As shown, DSC has an endothermic signal peak accompanied by an exothermic one at 190°C to 240°C; TGA has a weight loss of 0.1% when heated to 150°C. The 1 1H NMR is as Figure 24 shown.

[0181] Example 9

[0182] Preparation method of malate: Weigh 21.3 mg of the compound shown in formula (I) and 4.0 mg of malic acid respectively, add them to 1 mL of acetone, stir at room temperature for 2 days, centrifuge the suspension, and vacuum-dry the solid at room temperature. The obtained solid is malate.

[0183] The X-ray powder diffraction data of the malate obtained in this example is shown in Table 9, and its XRPD pattern is as Figure 25 shown.

[0184] Table 9

[0185]

[0186]

[0187] The DSC / TGA of malate is as Figure 26 shown. DSC has an endothermic melting signal peak at about 206°C; TGA has basically no weight loss when heated to 150°C. The 1 1H NMR of malate is as Figure 27 shown.

[0188] Example 10

[0189] Preparation method of fumarate: Weigh 21.5 mg of the compound shown in formula (I) and 3.7 mg of fumaric acid respectively, add them to 1 mL of n-heptane, stir at room temperature for 2 days, centrifuge the suspension, and vacuum-dry the solid at room temperature. The obtained solid is fumarate.

[0190] The X-ray powder diffraction data of the fumarate obtained in this example is shown in Table 10, and its XRPD pattern is as Figure 28 shown.

[0191] Table 10

[0192]

[0193] The DSC / TGA of fumarate is as Figure 29 shown. DSC has an endothermic melting signal peak at about 248°C; TGA has basically no weight loss when heated to 200°C. The 1 1H NMR of fumarate is as Figure 30 shown.

[0194] Example 11

[0195] Preparation method of sulfate: Weigh 21.3 mg of the compound shown in formula (I) and 66 μL of 1 M sulfuric acid respectively, add them to 1 mL of isopropanol, stir at room temperature for 2 days, centrifuge the suspension, and vacuum-dry the solid at room temperature. The obtained solid is the sulfate.

[0196] The X-ray powder diffraction data of the sulfate obtained in this example are shown in Table 11, and its XRPD pattern is as Figure 31 shown.

[0197] Table 11

[0198]

[0199] The DSC / TGA of the sulfate is as Figure 32 shown. There is an endothermic signal peak accompanied by an exothermic and then an endothermic signal when heating to 200 °C to 265 °C in DSC; there is basically no weight loss when heating to 150 °C in TGA. The 1 1H NMR of the sulfate is as Figure 33 shown.

[0200] Preliminary investigation on solubility in Example 12

[0201] Comparative study on the solubility of the compound shown in formula (I) in the present invention, including phosphate, tartrate, malonate, 1,2-ethanedisulfonate, p-toluenesulfonate, hydrochloride, mesylate, hydrobromide, malate, fumarate, and sulfate.

[0202] Prepare saturated solutions of the phosphate prepared in Example 1, the tartrate prepared in Example 2, the malonate prepared in Example 3, the 1,2-ethanedisulfonate prepared in Example 4, the p-toluenesulfonate prepared in Example 5, the hydrochloride prepared in Example 6, the mesylate prepared in Example 7, the hydrobromide prepared in Example 8, the malate prepared in Example 9, the fumarate prepared in Example 10, and the sulfate sample prepared in Example 11 with high-purity water respectively, and determine the solubility of each saturated solution by high-performance liquid chromatography. Prepare saturated solutions of the free base in Patent CN109415362B and the citrate crystal form C2 sample in Patent KR10-2496869 with high-purity water respectively, and determine the content of the sample in the saturated solution by high-performance liquid chromatography. The experimental results are shown in Table 12.

[0203] Table 12

[0204]

[0205]

[0206] The experimental results show that, compared with the free base and citrate, the phosphates, sulfates, 1,2-ethanedisulfonates, hydrochlorides, mesylates, hydrobromides, malates, fumarates, etc. of the present invention all have improved solubility.

[0207] For the development of injectables, the solubility of the active pharmaceutical ingredient is crucial. Especially for small volume injections, in order to meet the requirements of patient compliance, the injection volume is usually no more than 5 mL. Therefore, the significantly improved solubility of the new salt forms provided by the present invention is beneficial for the further development of small volume injections and reducing the injection volume.

[0208] Stability study of Example 13

[0209] Comparative study on the C2 stability of the phosphates, sulfates, hydrochlorides, hydrobromides, fumarates, malates, mesylates, tartrates, malonates, p-toluenesulfonates, 1,2-ethanedisulfonates, etc. of the compound shown in formula (I) prepared in the examples of the present invention with the free base in Patent CN109415362B and the citrate in Patent KR10-2496869.

[0210] Take the phosphate prepared in Example 1, the tartrate prepared in Example 2, the malonate prepared in Example 3, the 1,2-ethanedisulfonate prepared in Example 4, the p-toluenesulfonate prepared in Example 5, the hydrochloride prepared in Example 6, the mesylate prepared in Example 7, the hydrobromide prepared in Example 8, the malate prepared in Example 9, the fumarate prepared in Example 10, the sulfate prepared in Example 11, the free base in Patent CN109415362B, and the citrate C2 in Patent KR10-2496869, and place them respectively under high temperature (60 °C), accelerated experiment (40 °C, 75% RH), high humidity (25 °C / 90% RH) and light (illuminance of 4500 ± 500 lx, ultraviolet light ≥ 0.7 w / m 2 ) conditions for 15 days, and sample to detect the appearance, purity and crystal form of the samples. The experimental results are shown in Tables 13 to 15. The experimental results show that various salts of the present invention all have a certain stability.

[0211] Table 13

[0212]

[0213] Table 14

[0214]

[0215] Table 15

[0216]

[0217]

[0218] Example 14 In Vivo Pharmacokinetics Test of the Compounds of the Present Invention

[0219] The experimental animals were male Sprague-Dawley rats, 6 to 8 weeks old, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Randomly divided into 2 groups based on rat body weight, with 6 animals in each group. Among them, the two groups were respectively given citrate C2 and phosphate of Example 1 by gavage, and the dosing dose was 10 mg / kg for both. The compound solvent was water for injection.

[0220] Before the start of the pharmacokinetics experiment, the rats were fasted overnight. Blood samples of 0.20 mL were collected at regular intervals by carotid artery puncture, and the blood sampling time points were 0.083 h, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, and 24 h. The blood samples were collected in sample tubes with EDTA, immediately centrifuged at 4000 rpm for 5 minutes at 4 °C, and then the plasma was transferred to another sample tube and stored at -20 °C or below.

[0221] The methods and instruments used are as follows:

[0222] Instrument: LC-MS / MS-05 (TQ6500+); Chromatographic column: ACQUITY UPLC HSS T3, 1.8 μm, 2.1 * 50 mm; Mass spectrometry method: ESI + ; Mobile phase: 0.1% FA water / 0.1% acetonitrile; Quantification method: internal standard method.

[0223] The experimental results are shown in Table 16.

[0224] Table 16 PK Parameters of Different Salt Forms

[0225]

[0226] It can be seen from the data in Table 16 that the phosphate of the present invention has a significant advantage in oral bioavailability compared with citrate. Drugs with high oral bioavailability can achieve the expected efficacy at a lower dosing dose; and a lower dosing dose can reduce the medication cost.

[0227] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope described in this specification.

Claims

1. A salt of the compound represented by formula (I) or a polymorph thereof; The salt of the compound represented by formula (I) is malonate, 1,2-ethanedisulfonate, hydrobromide or malate; The polymorph of the salt of the compound represented by formula (I) is a polymorph of the phosphate, sulfate, tartrate, malonate, 1,2-ethanedisulfonate, p-toluenesulfonate, hydrochloride, methanesulfonate, hydrobromide, malate or fumarate of the compound represented by formula (I); 2. The salt or polymorph thereof according to claim 1, characterized in that The polymorph of the salt of the compound represented by formula (I) is a phosphate crystal form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1°±0.2°, 10.8°±0.2°, 11.5°±0.2°, 17.6°±0.2°, 22.0°±0.2°, 22.6°±0.2°; preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1°±0.2°, 10.8°±0.2°, 11.5°±0.2°, 15.9°±0.2°, 16.8°±0.2°, 17.6°±0.2°, 22.0°±0.2°, 22.6°±0.2°; Preferably, the X-ray powder diffraction pattern of the phosphate crystal form further includes one, two or more of the following characteristic diffraction peaks at 2θ angles: 11.8°±0.2°, 19.4°±0.2°, 19.8°±0.2°, 21.1°±0.2°, 23.1°±0.2°, 23.9°±0.2°, 24.5°±0.2°, 25.3°±0.2°, 26.9°±0.2°; Preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1°±0.2°, 10.8°±0.2°, 11.5°±0.2°, 15.9°±0.2°, 16.8°±0.2°, 17.6°±0.2°, 22.0°±0.2°, 22.6°±0.2°, 23.1°±0.2°, 25.3°±0.2°, 26.9°±0.2°; Preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 8.1°±0.2°, 10.8°±0.2°, 11.5°±0.2°, 11.8°±0.2°, 15.9°±0.2°, 16.8°±0.2°, 17.6°±0.2°, 19.4°±0.2°, 19.8°±0.2°, 21.1°±0.2°, 22.0°±0.2°, 22.6°±0.2°, 23.1°±0.2°, 23.9°±0.2°, 24.5°±0.2°, 25.3°±0.2°, 26.9°±0.2°; Preferably, the X-ray powder diffraction pattern of the phosphate crystal form has characteristic diffraction peaks at the following 2θ angles: 10.8°±0.2°, 11.5°±0.2°, 17.6°±0.2°, 21.9°±0.2°, 22.0°±0.2°, 22.6°±0.2°; Preferably, the X-ray powder diffraction pattern of the phosphate crystal form also includes the following one, two or more characteristic diffraction peaks at 2θ angles: 8.1°±0.2°, 15.9°±0.2°, 16.8°±0.2°, 23.1°±0.2°, 25.3°±0.2°, 26.9°±0.2°; Preferably, the X-ray powder diffraction pattern analysis data of the phosphate crystal form is shown in Table 1, wherein the error range of each characteristic diffraction peak 2θ is ±0.2°; Preferably, the phosphate crystal form has an X-ray powder diffraction pattern substantially as shown in Figure 1; Preferably, the differential scanning calorimetry diagram of the phosphate crystal form comprises an endothermic peak at 206.9°C ± 3°C; Preferably, the differential scanning calorimetry diagram of the phosphate crystal form is shown in Figure 2.

3. The salt or polymorph thereof according to claim 1, characterized in that The polymorph of the salt of the compound represented by formula (I) is a sulfate salt of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the sulfate salt has characteristic diffraction peaks at the following 2θ angles: 7.0°±0.2°, 14.2°±0.2°, 20.3°±0.2°, 21.0°±0.2°, 22.2°±0.2°, 23.7°±0.2°, 24.9° ±0.2°; preferably, the X-ray powder diffraction pattern of the sulfate crystalline form has characteristic diffraction peaks at the following 2θ angles: 7.0°±0.2°, 14.2°±0.2°, 20.3°±0.2°, 21.0°±0.2°, 22.2°±0.2°, 22.5°±0.2°, 23.7°±0.2°, 24.9°±0.2°, 26.0°±0.2°; Preferably, the X-ray powder diffraction pattern of the sulfate salt crystalline form further includes one, two or more of the following characteristic diffraction peaks at 2θ angles: 9.9°±0.2°, 18.0°±0.2°, 19.0°±0.2°, 22.5°±0.2°, 24.5°±0.2°, 25.5°±0.2°, 26.0°±0.2°, 27.7°±0.2°; Preferably, the X-ray powder diffraction pattern of the sulfate salt crystalline form further includes one, two or more of the following characteristic diffraction peaks at 2θ angles: 9.9°±0.2°, 15.8°±0.2°, 18.0°±0.2°, 19.0°±0.2°, 20.0°±0.2°, 21.9°±0.2°, 24.5°±0.2°, 25.5°±0.2°, 27.7°±0.2°; Preferably, the X-ray powder diffraction pattern of the sulfate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 7.0°±0.2°, 9.9°±0.2°, 14.2°±0.2°, 18.0°±0.2°, 19.0°±0.2°, 20.3°±0.2°, 21.0°±0.2°, 22.2°±0.2°, 22.5°±0.2°, 23.7°±0.2°, 24.9°±0.2°, 26.0°±0.2°. Preferably, the X-ray powder diffraction pattern of the sulfate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 7.0°±0.2°, 9.9°±0.2°, 14.2°±0.2°, 15.8°±0.2°, 18.0°±0.2°, 19.0°±0.2°, 20.0°±0.2°, 20.3°±0.2°, 21.0°±0.2°, 21.9°±0.2°, 22.2°±0.2°, 22.5°±0.2°, 23.7°±0.2°, 24.5°±0.2°, 24.9°±0.2°, 25.5°±0.2°, 26.0°±0.2°, 27.7°±0.2°; Preferably, the X-ray powder diffraction pattern analysis data of the sulfate salt crystal form is shown in Table 11, wherein the error range of each characteristic diffraction peak 2θ is ±0.2°; Preferably, the sulfate salt crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 31; Preferably, the differential scanning calorimetry diagram of the sulfate salt crystal form is shown in Figure 32.

4. The salt or polymorph thereof according to claim 1, characterized in that The polymorph of the salt of the compound represented by formula (I) is a hydrochloride salt of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the hydrochloride salt has characteristic diffraction peaks at the following 2θ angles: 10.4°±0.2°, 17.1°±0.2°, 20.1°±0.2°, 24.4°±0.2°, 24.6°±0.2°, 26.7°±0.2°; preferably, the X-ray powder diffraction pattern of the hydrochloride salt has characteristic diffraction peaks at the following 2θ angles: 10.4°±0.2°, 17.1°±0.2°, 20.1°±0.2°, 20.6°±0.2°, 23.0°±0.2°, 24.4°±0.2°, 24.6°±0.2°, 26.7°±0.2°; Preferably, the X-ray powder diffraction pattern of the hydrochloride salt crystalline form further includes the following one, two or more characteristic diffraction peaks at 2θ angles: 10.9°±0.2°, 15.2°±0.2°, 15.6°±0.2°, 17.6°±0.2°, 19.4°±0.2°, 20.8°±0.2°, 21.8°±0.2°, 22.1°±0.2°, 25.4°±0.2°; According to an embodiment of the present invention, the X-ray powder diffraction pattern of the hydrochloride salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 10.4°±0.2°, 10.9°±0.2°, 17.1°±0.2°, 17.6°±0.2°, 19.4°±0.2°, 20.1°±0.2°, 20.6°±0.2°, 23.0°±0.2°, 24.4°±0.2°, 24.6°±0.2°, 25.4°±0.2°, 26.7°±0.2°; Preferably, the X-ray powder diffraction pattern of the hydrochloride salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 10.4°±0.2°, 10.9°±0.2°, 15.2°±0.2°, 15.6°±0.2°, 17.1°±0.2°, 17.6°±0.2°, 19.4°±0.2°, 20.1°±0.2°, 20.6°±0.2°, 20.8°±0.2°, 21.8°±0.2°, 22.1°±0.2°, 23.0°±0.2°, 24.4°±0.2°, 24.6°±0.2°, 25.4°±0.2°, 26.7°±0.2°; Preferably, the X-ray powder diffraction pattern of the hydrochloride salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 10.4°±0.2°, 20.1°±0.2°, 23.0°±0.2°, 24.4°±0.2°, 24.6°±0.2°, 26.7°±0.2°; preferably, the X-ray powder diffraction pattern of the hydrochloride salt crystalline form also includes the following characteristic diffraction peaks at one, two or more 2θ angles: X-ray diffraction peaks: 10.9°±0.2°, 17.1°±0.2°, 19.4°±0.2°, 20.6°±0.2°, 20.8°±0.2°, 21.8°±0.2°, 22.0°±0.2°, 25.4°±0.2°; Preferably, the X-ray powder diffraction pattern analysis data of the hydrochloride salt crystalline form is shown in Table 6, wherein the error range of each characteristic diffraction peak 2θ is ±0.2°; Preferably, the hydrochloride salt crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 16; Preferably, the differential scanning calorimetry diagram of the hydrochloride salt crystalline form comprises an endothermic peak at 215°C±3°C ( FIG. 17 ); Preferably, the differential scanning calorimetry diagram of the hydrochloride salt crystalline form is shown in Figure 17.

5. The salt or polymorph thereof according to claim 1, characterized in that The polymorph of the salt of the compound represented by formula (I) is a mesylate salt of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the mesylate salt has characteristic diffraction peaks at the following 2θ angles: 12.5°±0.2°, 16.9°±0.2°, 18.0°±0.2°, 18.7°±0.2°, 19.8°±0.2°, 23.1°±0.2°, 23.4°±0.2°, 24.0°±0.2°; preferably, the X-ray powder diffraction pattern of the mesylate salt also includes one, two or more characteristic diffraction peaks at the following 2θ angles: 6.4°±0.2°, 6.6°±0.2°, 11.8 ° ± 0.2°, 16.1° ± 0.2°, 17.5° ± 0.2°, 18.9° ± 0.2°, 20.0° ± 0.2°, 20.9° ± 0.2°, 22.7° ± 0.2°, 24.4° ± 0.2°, 25.2° ± 0.2°, 26.0° ± 0.2°; Preferably, the X-ray powder diffraction pattern of the mesylate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.4° ± 0.2°, 6.6° ± 0.2°, 11.8° ± 0.2°, 12.5° ± 0.2°, 16.1° ± 0.2°, 16.9° ± 0.2°, 17.5° ± 0.2°, 18.0° ± 0.2°, 18. 7°±0.2°, 18.9°±0.2°, 19.8°±0.2°, 20.0°±0.2°, 20.9°±0.2°, 22.7°±0.2°, 23.1°±0.2°, 23.4°±0.2°, 24.0°±0.2°, 24.4°±0.2°, 25.2°±0.2°, 26.0°±0.2°; preferably, the X-ray powder diffraction pattern of the mesylate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 12.5°±0.2°, 16.9°±0.2°, 18.0°±0.2°, 18.7°±0.2°, 19.8°±0.2°, 23.1°±0.2° , 23.4°±0.2°, 24.0°±0.2°, 25.2°±0.2°; preferably, the X-ray powder diffraction pattern of the mesylate salt crystalline form also includes the following one, two or more characteristic diffraction peaks at 2θ angles: 6.4°±0.2°, 6.6°±0.2°, 11.8°±0.2°, 13.5°±0.2°, 16.1°±0.2°, 16.3°±0.2°, 17.5°±0.2°, 18.9°±0.2°, 20.0°±0.2°, 20.6°±0.2°, 20.9°±0.2°, 22.7°±0.2°, 24.4°±0.2°, 26.0°±0.2°; Preferably, the X-ray powder diffraction pattern analysis data of the mesylate salt crystalline form is shown in Table 7; preferably, the mesylate salt crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 19; preferably, the differential scanning calorimetry diagram of the mesylate salt crystalline form is shown in Figure 20; Preferably, the polymorph of the salt of the compound represented by formula (I) is a hydrobromide salt of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the hydrobromide salt has characteristic diffraction peaks at the following 2θ angles: 10.4°±0.2°, 15.5°±0.2°, 20.1°±0.2°, 20.5°±0.2°, 23.2°±0.2°, 24.3°±0.2°, 24.5°±0.2°, 26.5°±0.2°; preferably, the X-ray powder diffraction pattern of the hydrobromide salt also includes one, two or more characteristic diffraction peaks at the following 2θ angles: 6.8°±0.2°, 14.7°±0.2°, 17.0°±0.2°, 18.6°±0.2°, 19.7°±0.2°, 22.9°±0.2°, 23.1°±0.2°, 24.2°±0.2°, 25.8°±0.2°, 26.9°±0.2°, 27. .2°,19.4°±0.2°,19.9°±0.2°,21.0°±0.2°,22.3°±0.2°,23.7°±0.2°,25.4°±0.2°,27.3°±0.2°,33.7°±0.2°; Preferably, the X-ray powder diffraction pattern of the hydrobromide salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.8°±0.2°, 10.4°±0.2°, 14.7°±0.2°, 15.5°±0.2°, 17.0°±0.2°, 19.4°±0.2°, 19.9°±0.2°, 20.1°±0.2°, 20.5°±0.2°, 21.0°±0.2°, 22 .3°±0.2°, 23.2°±0.2°, 23.7°±0.2°, 24.3°±0.2°, 24.5°±0.2°, 25.4°±0.2°, 26.5°±0.2°, 27.3°±0.2°, 33.7°±0.2°; preferably, the X-ray powder diffraction pattern of the hydrobromide salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 20.1°±0.2°, 20.5°±0.2°, 23.2°±0.2°, 24.3°±0.2°, 24.5°±0.2°, 25.4°±0.2°, 26.5°±0.2°; preferably, the X-ray powder diffraction pattern of the hydrobromide salt crystalline form also includes the following characteristic diffraction peaks at one, two or more 2θ angles: 6.8°±0.2°, 10.4°±0.2°, 14.7°±0.2°, 15.5°±0.2°, 17.0°±0.2°, 19.4°±0.2°, 19.9°±0.2°, 21.0°±0.2°, 22.3°±0.2°, 23.7°±0.2°, 27.3°±0.2°, 33.7°±0.2°; preferably, the X-ray powder diffraction pattern analysis data of the hydrobromide salt crystalline form are shown in Table 8; preferably, the hydrobromide salt crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 22; preferably, the differential scanning calorimetry diagram of the hydrobromide salt is shown in Figure 23; Preferably, the polymorph of the salt of the compound represented by formula (I) is a malate crystalline form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the malate crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.8°±0.2°, 10.0°±0.2°, 14.6°±0.2°, 18.3°±0.2°, 19.7°±0.2°, 23.1°±0.2°, 23.7°±0.2°, 25.2°±0.2°; preferably, the X-ray powder diffraction pattern of the malate crystalline form also includes the following characteristic diffraction peaks at one, two or more 2θ angles: Preferably, the X-ray powder diffraction pattern of the malate crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.8°±0.2°, 10.0°±0.2°, 10.2°±0.2°, 14.6°±0.2°, 18.3°±0.2°, 18.8°±0.2°, 19.1°±0.2°, 19.7°±0.2°, 20.4°±0.2°, 21.7°±0.2°, 25.6°±0.2°; preferably, the X-ray powder diffraction pattern of the malate crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.8°±0.2°, 10.0°±0.2°, 10.2°±0.2°, 14.6°±0.2°, 18.3°±0.2°, 18.8°±0.2°, 19.1°±0.2°, 19.7°±0.2°, 20.4°±0.2°, 21. 7°±0.2°, 23.1°±0.2°, 23.7°±0.2°, 25.2°±0.2°, 25.6°±0.2°; preferably, the X-ray powder diffraction pattern of the malate crystalline form has characteristic diffraction peaks at the following 2θ angles: 10.2°±0.2°, 14.6°±0.2°, 18.3°±0.2°, 23.1°±0.2°, 23.7°±0.2°, 25.2°±0.2°; the X-ray powder diffraction pattern of the malate crystalline form also includes the following one, two or more characteristic diffraction peaks at 2θ angles: 6.8°±0.2°, 10.0°±0.2°, 18.8°±0.2°, 19.1°±0.2°, 19.7°±0.2°, 20.4°±0.2°, 21.7°±0.2°, 25.6°±0.2°; preferably, the X-ray powder diffraction pattern analysis data of the malate crystalline form are shown in Table 9; preferably, the malate crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 25; preferably, the differential scanning calorimetry diagram of the malate crystalline form comprises an endothermic peak of 206°C±3°C (Figure 26); preferably, the differential scanning calorimetry diagram of the malate crystalline form is shown in Figure 26.

6. The salt or polymorph thereof according to claim 1, characterized in that The polymorph of the salt of the compound represented by formula (I) is a tartrate salt of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the tartrate salt has characteristic diffraction peaks at the following 2θ angles: 6.9°±0.2°, 10.1°±0.2°, 14.2°±0.2°, 14.7°±0.2°, 18.4°±0.2°, 18.8°±0.2°, 19.9°±0.2°, 20.7°±0.2°, 21.9°±0.2°, 22.5°±0.2°, 23.9°±0.2°; preferably, the X-ray powder diffraction pattern of the tartrate salt also includes one, two or more of the following: Characteristic diffraction peaks at multiple 2θ angles: 9.9°±0.2°, 18.6°±0.2°, 24.7°±0.2°, 25.8°±0.2°, 30.0°±0.2°, 30.5°±0.2°; Preferably, the X-ray powder diffraction pattern of the tartrate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.9°±0.2°, 9.9°±0.2°, 10.1°±0.2°, 14.2°±0.2°, 14.7°±0.2°, 18.4°±0.2°, 18.6°±0.2°, 18.8°±0.2°, 19.9°±0.2°, 20.7°±0.2°, 21 .9°±0.2°, 22.5°±0.2°, 23.9°±0.2°, 24.7°±0.2°, 25.8°±0.2°, 30.0°±0.2°, 30.5°±0.2°; preferably, the X-ray powder diffraction pattern of the tartrate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.9°±0.2°, 14.2°±0.2°, 14.7°±0.2°, 18.4°±0.2°, 19.9°±0.2°, 20.7°±0.2°, 23.9°±0.2°, 24.7°±0.2°; preferably, the X-ray powder diffraction pattern of the tartrate salt crystalline form also includes characteristic diffraction peaks at the following 2θ angles: The following characteristic diffraction peaks at one, two or more 2θ angles: 9.9°±0.2°, 10.1°±0.2°, 18.6°±0.2°, 18.8°±0.2°, 21.9°±0.2°, 22.5°±0.2°, 25.8°±0.2°; preferably, the X-ray powder diffraction pattern analysis data of the tartrate salt crystalline form is shown in Table 2; preferably, the tartrate salt crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 4; preferably, the differential scanning calorimetry diagram of the tartrate salt crystalline form comprises an endothermic peak of 212.2°C±3°C (Figure 5); preferably, the differential scanning calorimetry diagram of the tartrate salt crystalline form is shown in Figure 5; Preferably, the polymorph of the salt of the compound represented by formula (I) is a malonate salt of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the malonate salt has characteristic diffraction peaks at the following 2θ angles: 6.9°±0.2°, 13.3°±0.2°, 13.8°±0.2°, 14.7°±0.2°, 19.6°±0.2°, 25.2°±0.2°, 25.4°±0.2°; preferably, the X-ray powder diffraction pattern of the malonate salt also includes the following: The characteristic diffraction peaks at one, two or more 2θ angles are: 9.8°±0.2°, 12.7°±0.2°, 18.3°±0.2°, 18.9°±0.2°, 26.8°±0.2°; preferably, the X-ray powder diffraction pattern of the malonate crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.9°±0.2°, 9.8°±0.2°, 12.7°±0.2°, 13.3°±0.2°, 13.8°±0.2°, 14.7°±0.2°, 18.3°±0.2°. 2°, 18.9°±0.2°, 19.6°±0.2°, 25.2°±0.2°, 25.4°±0.2°, 26.8°±0.2°; preferably, the X-ray powder diffraction pattern of the malonate crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.9°±0.2°, 13.3°±0.2°, 13.8°±0.2°, 19.6°±0.2°, 25.2°±0.2°, 25.4°±0.2°; preferably, the X-ray powder diffraction pattern of the malonate crystalline form has characteristic diffraction peaks at the following 2θ angles: The spectrum also includes the following one, two or more characteristic diffraction peaks at 2θ angles: 9.8°±0.2°, 12.7°±0.2°, 14.7°±0.2°, 18.3°±0.2°, 18.9°±0.2°, 26.8°±0.2°; preferably, the X-ray powder diffraction spectrum analysis data of the malonate crystalline form is shown in Table 3; preferably, the malonate crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 7; preferably, the differential scanning calorimetry diagram of the malonate crystalline form is shown in Figure 8; Preferably, the polymorph of the salt of the compound represented by formula (I) is a 1,2-ethanedisulfonate salt of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate salt has characteristic diffraction peaks at the following 2θ angles: 6.6°±0.2°, 12.0°±0.2°, 15.8°±0.2°, 17.1°±0.2°, 19.8°±0.2°, 20.1°±0.2°, 23.0°±0.2°, 23.5°±0.2°; preferably, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate salt further includes one, two or more characteristic diffraction peaks at 2θ angles: 13.2°±0.2°, 14.6°±0.2°, 15.8°±0.2°, 17.1°±0.2°, 19.8°±0.2°, 20.1°±0.2°, 23.0°±0.2°, 23.5°±0.2°. 0.2°, 13.4°±0.2°, 16.0°±0.2°, 18.2°±0.2°, 20.3°±0.2°, 23.9°±0.2°; Preferably, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 6.6°±0.2°, 12.0°±0.2°, 13.2°±0.2°, 13.4°±0.2°, 15.8°±0.2°, 16.0°±0.2°, 17.1°±0.2°, 18.2°±0.2°, 19.8°±0.2°, 20.1°±0.2°, 20.3°±0.2°, 23.0°±0.2° , 23.5°±0.2°, 23.9°±0.2°; preferably, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate salt crystal form has characteristic diffraction peaks at the following 2θ angles: 6.6°±0.2°, 12.0°±0.2°, 17.1°±0.2°, 19.8°±0.2°, 20.1°±0.2°, 23.5°±0.2°; preferably, the X-ray powder diffraction pattern of the 1,2-ethanedisulfonate salt crystal form also includes the following one, two or more characteristic diffraction peaks at 2θ angles: 13.2°±0.2°, 13.4°±0.2°, 15.8°±0.2°, 16.0°±0.2°, 18.0°±0 .2°, 18.2°±0.2°, 20.3°±0.2°, 23.0°±0.2°, 23.9°±0.2°, 26.1°±0.2°, 26.4°±0.2°, 26.9°±0.2°; preferably, the X-ray powder diffraction pattern analysis data of the 1,2-ethanedisulfonate salt crystalline form is shown in Table 4; preferably, the 1,2-ethanedisulfonate salt crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 10; preferably, the differential scanning calorimetry diagram of the 1,2-ethanedisulfonate salt crystalline form comprises an endothermic peak at 279°C±3°C (Figure 11); preferably, the differential scanning calorimetry diagram of the 1,2-ethanedisulfonate salt crystalline form is shown in Figure 11; Preferably, the polymorph of the salt of the compound represented by formula (I) is a p-toluenesulfonate crystalline form of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the p-toluenesulfonate crystalline form has characteristic diffraction peaks at the following 2θ angles: 7.4°±0.2°, 9.7°±0.2°, 11.1°±0.2°, 13.8°±0.2°, 19.3°±0.2°, 24.0°±0.2°, 24.4°±0.2°, 24.9°±0.2°, 26.6°±0.2°; preferably, the X-ray powder diffraction pattern of the p-toluenesulfonate crystalline form also includes the following characteristic diffraction peaks at one, two or more 2θ angles: The X-ray powder diffraction peaks are as follows: 12.7°±0.2°, 21.0°±0.2°, 21.5°±0.2°, 21.9°±0.2°, 22.1°±0.2°, 22.4°±0.2°, 22.7°±0.2°, 26.0°±0.2°, 27.9°±0.2°; preferably, the X-ray powder diffraction pattern of the p-toluenesulfonate crystalline form also includes the following one, two or more characteristic diffraction peaks at 2θ angles: 4.0°±0.2°, 12.7°±0.2°, 13.0°±0.2°, 15.7°±0.2°, 17.0°±0.2°, 18.0°±0.2°, 20.0°±0.2°. 2°, 20.4°±0.2°, 21.0°±0.2°, 21.5°±0.2°, 21.9°±0.2°, 22.1°±0.2°, 22.4°±0.2°, 22.7°±0.2°, 25.3°±0.2°, 26.0°±0.2°, 27.9°±0.2°; preferably, the X-ray powder diffraction pattern of the p-toluenesulfonate crystalline form has characteristic diffraction peaks at the following 2θ angles: 7.4°±0.2°, 9.7°±0.2°, 11.1°±0.2°, 12.7°±0.2°, 13.8°±0.2°, 19.3°±0.2°, 21.0°±0.2°, 2 .2°, 21.5°±0.2°, 21.9°±0.2°, 22.1°±0.2°, 22.4°±0.2°, 22.7°±0.2°, 24.0°±0.2°, 24.4°±0.2°, 24.9°±0.2°, 26.0°±0.2°, 26.6°±0.2°, 27.9°±0.2°; preferably, the X-ray powder diffraction pattern analysis data of the p-toluenesulfonate salt crystalline form are shown in Table 5; preferably, the p-toluenesulfonate salt crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 13; preferably, the differential scanning calorimetry diagram of the p-toluenesulfonate salt crystalline form is shown in Figure 14; Preferably, the polymorph of the salt of the compound represented by formula (I) is a fumarate salt of the compound represented by formula (I); preferably, the X-ray powder diffraction pattern of the fumarate salt has characteristic diffraction peaks at the following 2θ angles: 9.4°±0.2°, 13.1°±0.2°, 14.1°±0.2°, 17.7°±0.2°, 21.6°±0.2°, 25.6°±0.2°; preferably, the X-ray powder diffraction pattern of the fumarate salt also includes one, two or more characteristic diffraction peaks at the following 2θ angles: 7.0°±0.2°, 11.2°±0.2°, 12.5°±0.2°, 13.6°±0.2°, 14.6°±0.2°, 15.7°±0.2°, 16.9°±0.2°, 17.8°±0.2°, 18.9°±0.2°, 19.1°±0.2°, 20. .2°,13.7°±0.2°,18.7°±0.2°,19.4°±0.2°,20.3°±0.2°,21.9°±0.2°,22.5°±0.2°,25.3°±0.2°; Preferably, the X-ray powder diffraction pattern of the fumarate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 7.0°±0.2°,9.4°±0.2°,11.2°±0.2°,12.5°±0.2°,13.1°±0.2°,13.7°±0.2°,14.1°±0.2°,17.7°±0.2°,18.7°±0.2°,1 9.4°±0.2°, 20.3°±0.2°, 21.6°±0.2°, 21.9°±0.2°, 22.5°±0.2°, 25.3°±0.2°, 25.6°±0.2°; preferably, the X-ray powder diffraction pattern of the fumarate salt crystalline form has characteristic diffraction peaks at the following 2θ angles: 9.4°±0.2°, 13.1°±0.2°, 17.7°±0.2°, 21.6°±0.2°, 25.6°±0.2°; preferably, the X-ray powder diffraction pattern of the fumarate salt crystalline form also includes the following one, two or more characteristic diffraction peaks at 2θ angles: 7.0 °±0.2°, 11.2°±0.2°, 12.5°±0.2°, 13.7°±0.2°, 14.1°±0.2°, 19.4°±0.2°, 20.3°±0.2°, 22.5°±0.2°; preferably, the X-ray powder diffraction pattern analysis data of the fumarate salt crystalline form are shown in Table 10; preferably, the fumarate salt crystalline form has an X-ray powder diffraction pattern substantially as shown in Figure 28; preferably, the differential scanning calorimetry diagram of the fumarate salt crystalline form comprises an endothermic peak of 248°C±3°C (Figure 29); preferably, the differential scanning calorimetry diagram of the fumarate salt crystalline form is shown in Figure 29.

7. A pharmaceutical composition comprising a salt of a compound of formula (I) according to any one of claims 1 to 6 or a polymorph thereof, and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant or a combination thereof; Preferably, the pharmaceutical composition is used to prevent and / or treat a disease caused by excessive gastric acid secretion; preferably, the disease is a gastrointestinal inflammatory disease or a gastric acid-related disease; Preferably, the gastrointestinal inflammatory disease or gastric acid-related disease includes, but is not limited to, peptic ulcer, gastric and duodenal ulcer, nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD) and non-invasive reflux disease (NERD).

8. Use of the salt of the compound represented by formula (I) or its polymorph according to any one of claims 1 to 6, or the pharmaceutical composition according to claim 7 in the preparation of a drug, wherein the drug is used to prevent and / or treat a disease caused by excessive gastric acid secretion; preferably, the disease is a gastrointestinal inflammatory disease or a gastric acid-related disease; Preferably, the gastrointestinal inflammatory disease or gastric acid-related disease includes, but is not limited to, peptic ulcer, gastric and duodenal ulcer, nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD) and non-invasive reflux disease (NERD).

9. A method for preventing and / or treating a disease caused by excessive gastric acid secretion, the method comprising administering to a patient an effective amount of a salt of a compound of formula (I) according to any one of claims 1 to 6 or a polymorph thereof, or a pharmaceutical composition according to claim 7; Preferably, the disease is a gastrointestinal inflammatory disease or a gastric acid-related disease; Preferably, the gastrointestinal inflammatory disease or gastric acid-related disease includes, but is not limited to, peptic ulcer, gastric and duodenal ulcer, nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD) and non-invasive reflux disease (NERD).

10. A method for preparing a salt of a compound represented by formula (I) or a polymorph thereof according to any one of claims 1 to 6: The preparation method of the salt comprises: Mixing the compound represented by formula (I) with a salt to obtain a salt of the compound represented by formula (I); The preparation method of the polymorph of the salt comprises: mixing the compound represented by formula (I) with the salt, and crystallizing to obtain the polymorph of the salt of the compound represented by formula (I).

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