Multiple crystal forms of S-indobufen salt as well as preparation method and application thereof

Abstract

The invention relates to multiple crystal forms of S-indobufen salt, a preparation method and application. The multiple crystal forms specifically relate to two potassium salt crystal forms, five calcium salt crystal forms, three magnesium salt crystal forms, four ammonium salt crystal forms, one choline salt crystal form Type A, four meglumine salt crystal forms, four lysine salt crystal forms, three betaine salt crystal forms, one diethylamine salt crystal form, five tromethamine salt crystal forms, two proline eutectic crystals, one urea eutectic crystal and one hexadecylamine salt. The S-indobufen salt has excellent solubility, compressibility and stability, low hygroscopicity and adhesiveness and very uniform particle size distribution, and has unique advantages in preparation and application.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical medicine, in particular to a crystal form of compound S-indobufen, i.e. GP-046, and a preparation method thereof. BACKGROUND

[0002] Thromboembolic disease is a kind of systemic disease affecting heart, brain and peripheral blood vessels, which is divided into arterial and venous types. High-risk patients of such diseases include patients with previous ischemic cerebrovascular disease, patients with atrial fibrillation, patients with long-term immobilization, patients with intermittent claudication, etc. Prevention is more important than treatment for such diseases, and anti-platelet drugs are widely used in the prevention of such thrombotic events.

[0003] In 2008, the American College of Chest Physicians (ACCP) guidelines proposed that indobufen is an effective cyclooxygenase-1 (Cox-1) inhibitor, which is comparable to standard-dose aspirin in terms of biochemical efficacy and clinical effectiveness. Compared with similar drugs, indobufen inhibits platelet factors and has an anti-platelet aggregation effect 2-5 times that of salicylic acid, and has a slightly shorter bleeding time. Compared with ticlopidine, there is no significant difference in oral clinical efficacy, but indobufen shows good tolerance.

[0004] Currently marketed indobufen is all racemic tablets. Although there are few reports on single configuration indobufen, through analysis of existing literature, it can be seen that there are differences in the biological activity of R-indobufen and S-indobufen (i.e. GP-046) in vivo. In 2001, it was reported that the study of indobufen enantiomers as racemic indobufen tablets in patients in vivo steady-state pharmacokinetics and bleeding time. The study proved that the inhibitory effect of dextro-indobufen on platelet aggregation was more obvious than that of indobufen, which could effectively block thrombus formation. The existing reported research results are all about the crystal form of racemic indobufen, and there is no public information about the crystal form of S- or R-indobufen. Based on the above conclusion, it is very potential to study the crystal form of single configuration indobufen. SUMMARY

[0005] The present application provides a salt of compound S-indobufen, which is selected from the group consisting of a methylglycine salt, a tromethamine salt, a proline co-crystal, a urea co-crystal, a potassium salt, a calcium salt, a magnesium salt, an ammonium salt, a choline salt, a lysine salt, a betaine salt, a diethylamine salt, and a hexadecylamine salt.

[0006] In one embodiment of the present application, the salts of S-indobufen include two potassium salt crystal forms (Type A / B), five calcium salt crystal forms (Type A~E), three magnesium salt crystal forms (Type A~C), four ammonium salt crystal forms (Type A~D), one choline salt crystal form Type A, four meglumine salt crystal forms (Type A / B / D / E), four lysine salt crystal forms (Type A~D), three betaine salt crystal forms (Type A~C), one diethylamine salt crystal form Type A, five tromethamine salt crystal forms (Type A~E), two proline co-crystals (Type A / B), one urea co-crystal Type A, and one hexadecylamine salt Type A of S-indobufen.

[0007] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at diffraction angles 2q of 7.4°±0.2°, 11.2°±0.2°, and 14.0°±0.2°.

[0008] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at one or two or three of diffraction angles 2q of 15.3°±0.2°, 18.2°±0.2°, and 22.9°±0.2°.

[0009] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at diffraction angles 2q of 15.3°±0.2°, 18.2°±0.2°, and 22.9°±0.2°.

[0010] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at one or two or three of diffraction angles 2q of 10.6°±0.2°, 16.7°±0.2°, and 22.2°±0.2°.

[0011] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at diffraction angles 2q of 10.6°±0.2°, 16.7°±0.2°, and 22.2°±0.2°.

[0012] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2-theta of 7.4°±0.2°, 10.6°±0.2°, 11.2°±0.2°, 14.0°±0.2°, 15.3°±0.2°, 16.7°±0.2°, 18.2°±0.2°, 22.2°±0.2°, 22.9°±0.2°.

[0013] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2-theta of 7.4°±0.2°, 10.6°±0.2°, 11.2°±0.2°, 14.0°±0.2°, 15.3°±0.2°, 16.7°±0.2°, 18.2°±0.2°, 22.2°±0.2°, 22.9°±0.2°.

[0014] The present application provides a meglumine salt Type A, wherein the molar ratio of S-indobufen to meglumine is: 0.8~1.2, preferably 0.9~1.1, more preferably 1.

[0015] The present application provides a meglumine salt Type A, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 1 .

[0016] When subjected to thermogravimetric analysis, the meglumine salt Type A has a mass loss gradient of about 0.31±0.2% when heated to 120±2 ºC, and its TGA is substantially as shown in Figure 2 .

[0017] When subjected to differential scanning calorimetry analysis, the meglumine salt Type A starts to melt when heated to about 148±2 ºC, and its DSC is substantially as shown in Figure 3 .

[0018] The present application provides a method for preparing the meglumine salt Type A, characterized in that, (1) the compound GP-046 in free form and meglumine are added to an acetone solvent system, and stirred at room temperature until the meglumine salt Type A is obtained; or (2) the meglumine salt is dissolved in a single or mixed solvent, and the solvent is evaporated at room temperature until the solid is precipitated, to obtain the meglumine salt Type A; or In one embodiment of the present application, the single solvent is methanol or trifluoroethanol.

[0019] In one embodiment of the present application, the mixed solvent is methanol / ethanol, methanol / isopropyl acetate, methanol / 2-methyltetrahydrofuran, methanol / acetonitrile, methanol / toluene, trifluoroethanol / methyl isobutyl ketone, trifluoroethanol / anisole, trifluoroethanol / 1,4-dioxane or trifluoroethanol / isopropanol.

[0020] In one embodiment of the present application, the volume ratio of methanol / ethanol is 1:1, the volume ratio of methanol / isopropyl acetate is 2:1, the volume ratio of methanol / 2-methyltetrahydrofuran is 2:1, the volume ratio of methanol / acetonitrile is 2:1, the volume ratio of methanol / toluene is 2:1, the volume ratio of trifluoroethanol / methyl isobutyl ketone is 2:1, the volume ratio of trifluoroethanol / anisole is 1:1, the volume ratio of trifluoroethanol / 1,4-dioxane is 1:1, and the volume ratio of trifluoroethanol / isopropanol is 1:1.

[0021] (3) dissolving the meglumine salt solid in a single or mixed solvent at high temperature, and then placing it under low temperature conditions to precipitate a solid to obtain meglumine salt Type A; or In one embodiment of the present application, the single solvent is ethanol.

[0022] In one embodiment of the present application, the mixed solvent is methanol / isopropanol, methanol / tetrahydrofuran, methanol / methyl isobutyl ketone, methanol / toluene, N,N-dimethylformamide / methylcyclohexyl ether or N,N-dimethylformamide / acetonitrile.

[0023] In one embodiment of the present application, the volume ratio of methanol / isopropanol is 1:10, the volume ratio of methanol / tetrahydrofuran is 1:10, the volume ratio of methanol / methyl isobutyl ketone is 11:10, the volume ratio of methanol / toluene is 1:2, the volume ratio of N,N-dimethylformamide / methylcyclohexyl ether is 7:5, and the volume ratio of N,N-dimethylformamide / acetonitrile is 7:5.

[0024] In one embodiment of the present application, the high temperature is 80 ºC; and the low temperature is -20 ºC.

[0025] (4) dissolving the meglumine salt solid in an alcoholic solvent, and adding dropwise an ester, ether, ketone, aromatic hydrocarbon or alkyl nitrile solvent to it under stirring until a solid is precipitated to obtain meglumine salt Type A; or In one embodiment of the present application, the alcoholic solvent is methanol or trifluoroethanol, the ester solvent is ethyl acetate or isopropyl acetate, the ether solvent is methylcyclohexyl ether, anisole or 2-methyltetrahydrofuran, the ketone solvent is methyl isobutyl ketone, the aromatic hydrocarbon solvent is toluene, and the alkyl nitrile solvent is acetonitrile.

[0026] (5) The meglumine salt solid is dissolved in a sulfoxide solvent, an amide solvent, and then added to a ketone, alcohol, ester, ether, aromatic hydrocarbon, alkyl nitrile, or halogenated hydrocarbon solvent under stirring until the meglumine salt Type A is precipitated.

[0027] In an embodiment of the present application, the sulfoxide solvent is dimethyl sulfoxide, the amide solvent is N,N-dimethylformamide, the ketone solvent is 2-butanone or methyl isobutyl ketone, the alcohol solvent is isobutyl alcohol, the ester solvent is isobutyl acetate, the ether solvent is tetrahydrofuran or methylcyclohexyl ether, the aromatic hydrocarbon solvent is toluene, the alkyl nitrile solvent is acetonitrile, and the halogenated hydrocarbon solvent is dichloromethane or 1,2-dichloroethane.

[0028] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at diffraction angles 2θ of 10.7°±0.2°, 16.2°±0.2°, and 22.5°±0.2°.

[0029] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at one or two or three of diffraction angles 2θ of 6.3°±0.2°, 12.0°±0.2°, and 13.9°±0.2°.

[0030] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at diffraction angles 2θ of 6.3°±0.2°, 12.0°±0.2°, and 13.9°±0.2°.

[0031] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at one or two or three of diffraction angles 2θ of 3.2°±0.2°, 21.4°±0.2°, and 27.3°±0.2°.

[0032] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at diffraction angles 2θ of 3.2°±0.2°, 21.4°±0.2°, and 27.3°±0.2°.

[0033] In one embodiment of the application, the meglumine salt Type B has an X-ray powder diffraction pattern with characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the following diffraction angles 2theta: 3.2°±0.2°, 6.3°±0.2°, 10.7°±0.2°, 12.0°±0.2°, 13.9°±0.2°, 16.2°±0.2°, 21.4°±0.2°, 22.5°±0.2°, 27.3°±0.2°.

[0034] In one embodiment of the application, the meglumine salt Type B has an X-ray powder diffraction pattern with characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the following diffraction angles 2theta: 3.2°±0.2°, 6.3°±0.2°, 10.7°±0.2°, 12.0°±0.2°, 13.9°±0.2°, 16.2°±0.2°, 21.4°±0.2°, 22.5°±0.2°, 27.3°±0.2°.

[0035] The meglumine salt Type B according to the application has a molar ratio of S-indobufen to meglumine of 0.8 to 1.2, preferably of 0.9 to 1.1, and more preferably of 1.

[0036] The meglumine salt Type B according to the application has an X-ray powder diffraction pattern substantially as shown in Figure 4 .

[0037] The meglumine salt Type B according to the application has a mass loss gradient of about 5.17 ± 0.2% when heated to 120 ± 2ºC, and a TGA substantially as shown in Figure 5 .

[0038] The meglumine salt Type B according to the application has an endothermic signal when heated to about 109 ± 2ºC and starts to melt when heated to about 150 ± 2ºC, and a DSC substantially as shown in Figure 6 .

[0039] The meglumine salt Type B according to the application is prepared by adding the compound GP-046 in free form and meglumine to a tetrahydrofuran solvent system and stirring at room temperature until the meglumine salt Type B is obtained.

[0040] In one embodiment of the application, the meglumine salt Type D has an X-ray powder diffraction pattern with characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the following diffraction angles 2theta: 6.2°±0.2°, 9.3°±0.2°, 12.5°±0.2°.

[0041] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2-theta of 13.9°±0.2°, 16.2°±0.2°, 27.1°±0.2°.

[0042] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2-theta of 13.9°±0.2°, 16.2°±0.2°, 27.1°±0.2°.

[0043] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2-theta of 10.8°±0.2°, 22.7°±0.2°, 30.1°±0.2°.

[0044] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2-theta of 10.8°±0.2°, 22.7°±0.2°, 30.1°±0.2°.

[0045] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2-theta of 6.2°±0.2°, 9.3°±0.2°, 10.8°±0.2°, 12.5°±0.2°, 13.9°±0.2°, 16.2°±0.2°, 22.7°±0.2°, 27.1°±0.2°, 30.1°±0.2°.

[0046] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2-theta of 6.2°±0.2°, 9.3°±0.2°, 10.8°±0.2°, 12.5°±0.2°, 13.9°±0.2°, 16.2°±0.2°, 22.7°±0.2°, 27.1°±0.2°, 30.1°±0.2°.

[0047] The present application provides a meglumine salt Type D, wherein the molar ratio of S-indobufen to meglumine is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0048] The present application provides a meglumine salt Type D, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 7

[0049] ​When subjected to thermogravimetric analysis, meglumine salt Type D has a mass loss gradient of about 15.39 ± 0.2% when heated to 120 ± 2ºC, and a TGA substantially as shown in Figure 8 .

[0050] When subjected to differential scanning calorimetry analysis, meglumine salt Type D has an endothermic signal when heated to about 99 ± 2ºC and begins to melt when heated to about 144 ± 2ºC, and a DSC substantially as shown in Figure 9 .

[0051] The present application provides a preparation method of meglumine salt Type D, characterized in that, The compound GP-046 in free form and meglumine are added to a chloroform solvent system, and stirred at room temperature until meglumine salt Type D is obtained.

[0052] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at diffraction angles 2θ of 7.4° ± 0.2°, 11.0° ± 0.2°, and 19.8° ± 0.2°.

[0053] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at one or two or three of diffraction angles 2θ of 12.7° ± 0.2°, 15.1° ± 0.2°, and 18.0° ± 0.2°.

[0054] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at diffraction angles 2θ of 12.7° ± 0.2°, 15.1° ± 0.2°, and 18.0° ± 0.2°.

[0055] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at one or two or three of diffraction angles 2θ of 3.7° ± 0.2°, 21.2° ± 0.2°, and 27.9° ± 0.2°.

[0056] In an embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at diffraction angles 2θ of 3.7° ± 0.2°, 21.2° ± 0.2°, and 27.9° ± 0.2°.

[0057] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at any 4 of 3.7°±0.2°, 7.4°±0.2°, 11.0°±0.2°, 12.7°±0.2°, 15.1°±0.2°, 18.0°±0.2°, 19.8°±0.2°, 21.2°±0.2°, 27.9°±0.2°, or 5 of them, or 6 of them, or 7 of them, or 8 of them, or 9 of them, in terms of diffraction angles 2Θ.

[0058] In one embodiment of the present application, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at 3.7°±0.2°, 7.4°±0.2°, 11.0°±0.2°, 12.7°±0.2°, 15.1°±0.2°, 18.0°±0.2°, 19.8°±0.2°, 21.2°±0.2°, 27.9°±0.2°, in terms of diffraction angles 2Θ.

[0059] The meglumine salt Type E provided by the present application, wherein the molar ratio of S-indobufen to meglumine is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0060] The meglumine salt Type E provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 10

[0061] When subjected to thermogravimetric analysis, the meglumine salt Type E has a mass loss gradient of about 1.74±0.2% when heated to 120±2 °C, and its TGA is substantially as shown in Figure 11

[0062] When subjected to differential scanning calorimetry analysis, the meglumine salt Type E starts to melt when heated to about 144±2 °C, and its DSC is substantially as shown in Figure 12

[0063] The preparation method of the meglumine salt Type E provided by the present application is characterized in that, heating the meglumine salt Type D to 120 °C to obtain the meglumine salt Type E.

[0064] In one embodiment of the present application, the heating rate is 10 °C / min.

[0065] In one embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type A has characteristic peaks at 4.0°±0.2°, 5.7°±0.2°, 9.1°±0.2°, in terms of diffraction angles 2Θ.

[0066] ​​​In one embodiment of the present application, the X-ray powder diffraction pattern of the salt of aminotriol Type A has characteristic peaks at diffraction angles 2-theta of 7.9°±0.2°, 20.2°±0.2°, 21.5°±0.2°.

[0067] In one embodiment of the present application, the X-ray powder diffraction pattern of the salt of aminotriol Type A has characteristic peaks at diffraction angles 2-theta of 7.9°±0.2°, 20.2°±0.2°, 21.5°±0.2°.

[0068] In one embodiment of the present application, the X-ray powder diffraction pattern of the salt of aminotriol Type A has characteristic peaks at diffraction angles 2-theta of 23.4°±0.2°, 24.3°±0.2°, 25.3°±0.2°.

[0069] In one embodiment of the present application, the X-ray powder diffraction pattern of the salt of aminotriol Type A has characteristic peaks at diffraction angles 2-theta of 23.4°±0.2°, 24.3°±0.2°, 25.3°±0.2°.

[0070] In one embodiment of the present application, the X-ray powder diffraction pattern of the salt of aminotriol Type A has characteristic peaks at diffraction angles 2-theta of 4.0°±0.2°, 5.7°±0.2°, 7.9°±0.2°, 9.1°±0.2°, 20.2°±0.2°, 21.5°±0.2°, 23.4°±0.2°, 24.3°±0.2°, 25.3°±0.2°.

[0071] In one embodiment of the present application, the X-ray powder diffraction pattern of the salt of aminotriol Type A has characteristic peaks at diffraction angles 2-theta of 4.0°±0.2°, 5.7°±0.2°, 7.9°±0.2°, 9.1°±0.2°, 20.2°±0.2°, 21.5°±0.2°, 23.4°±0.2°, 24.3°±0.2°, 25.3°±0.2°.

[0072] The present application provides a salt of aminotriol Type A, wherein the molar ratio of S-indobufen to aminotriol is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0073] The present application provides a salt of aminotriol Type A, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 13

[0074] ​When subjected to thermal gravimetric analysis, the tromethamine salt Type A has a mass loss gradient of about 3.73 ± 0.2% when heated to 120 ± 2 °C, its TGA is substantially as shown in Figure 14 .

[0075] When subjected to differential scanning calorimetric analysis, the tromethamine salt Type A has exothermic and endothermic signals near 110 ± 2 °C, endothermic and exothermic signals near 147 ± 2 °C, and begins to melt near 154 ± 2 °C, its DSC is substantially as shown in Figure 15 .

[0076] The present application provides a method for preparing the tromethamine salt Type A, characterized in that, dissolving the tromethamine salt solid in a single or mixed solvent, volatilizing the solvent at room temperature until the solid is precipitated, to obtain the tromethamine salt Type A.

[0077] In an embodiment of the present application, the single solvent is methanol or trifluoroethanol.

[0078] In an embodiment of the present application, the mixed solvent is trifluoroethanol / isopropyl acetate, trifluoroethanol / acetonitrile, trifluoroethanol / toluene, methanol / ethyl lactate or methanol / isopropyl alcohol.

[0079] In an embodiment of the present application, the volume ratio of trifluoroethanol / isopropyl acetate is 19:5, the volume ratio of trifluoroethanol / acetonitrile is 11:5, the volume ratio of trifluoroethanol / toluene is 2:1, the volume ratio of methanol / ethyl lactate is 2:1, and the volume ratio of methanol / isopropyl alcohol is 9:5.

[0080] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type B has characteristic peaks at diffraction angles 2θ of 7.6° ± 0.2°, 15.2° ± 0.2°, and 22.1° ± 0.2°.

[0081] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type B has characteristic peaks at diffraction angles 2θ of one or two or three of 12.8° ± 0.2°, 17.7° ± 0.2°, and 19.7° ± 0.2°.

[0082] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type B has characteristic peaks at diffraction angles 2θ of 12.8° ± 0.2°, 17.7° ± 0.2°, and 19.7° ± 0.2°.

[0083] In an embodiment of the application, the X-ray powder diffraction pattern of the Troxaptadine salt Type B has a characteristic peak at one or two or three of the diffraction angles 2-theta of 6.4°±0.2°, 22.9°±0.2°, 27.3°±0.2°.

[0084] In an embodiment of the application, the X-ray powder diffraction pattern of the Troxaptadine salt Type B has a characteristic peak at one or two or three of the diffraction angles 2-theta of 6.4°±0.2°, 22.9°±0.2°, 27.3°±0.2°.

[0085] In an embodiment of the application, the X-ray powder diffraction pattern of the Troxaptadine salt Type B has a characteristic peak at one or two or three of the diffraction angles 2-theta of 6.4°±0.2°, 22.9°±0.2°, 27.3°±0.2°.

[0086] In an embodiment of the application, the X-ray powder diffraction pattern of the Troxaptadine salt Type B has a characteristic peak at one or two or three of the diffraction angles 2-theta of 6.4°±0.2°, 22.9°±0.2°, 27.3°±0.2°.

[0087] The present application provides a Troxaptadine salt Type B, wherein the molar ratio of S-indobufen to Troxaptadine is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0088] The present application provides a Troxaptadine salt Type B, characterized by an X-ray powder diffraction pattern substantially as shown in Figure 16 .

[0089] When subjected to thermogravimetric analysis, the Troxaptadine salt Type B has a mass loss gradient of about 0.09±0.2% when heated to 120 ±2ºC, its TGA being substantially as shown in Figure 17 .

[0090] When subjected to differential scanning calorimetry analysis, the Troxaptadine salt Type B starts to melt when heated to about 156 ±2ºC, its DSC being substantially as shown in Figure 18 .

[0091] The application provides a preparation method of the Tinzaparin Type B salt, characterized in that, (1) the compound GP-046 free state and the Tinzaparin are added into an acetonitrile solvent system, and stirred at room temperature until the Tinzaparin salt Type B is obtained; or (2) the Tinzaparin salt solid is dissolved in a single or mixed solvent at high temperature, and then placed in a low-temperature condition to precipitate a solid, so that the Tinzaparin salt Type B is obtained; or In an embodiment of the application, the single solvent is isopropyl alcohol or acetone.

[0092] In an embodiment of the application, the mixed solvent is ethanol / n-heptane, trifluoroethanol / methyl isobutyl ketone, trifluoroethanol / toluene, methanol / methylcyclohexyl ether or methanol / acetonitrile.

[0093] In an embodiment of the application, the volume ratio of the ethanol / n-heptane is 9:5, the volume ratio of the trifluoroethanol / methyl isobutyl ketone is 14:5, the volume ratio of the trifluoroethanol / toluene is 1:2, the volume ratio of the methanol / methylcyclohexyl ether is 1:1, and the volume ratio of the methanol / acetonitrile is 1:2.

[0094] In an embodiment of the application, the high temperature is 80 °C, and the low temperature is -20 °C.

[0095] (3) the Tinzaparin salt solid is dissolved in an amide solvent, and then placed in an ether, halogenated hydrocarbon or alkyl nitrile solvent atmosphere for gas-liquid diffusion until a solid is precipitated, so that the Tinzaparin salt Type B is obtained; or In an embodiment of the application, the amide solvent is N,N-dimethylacetamide, the ether solvent is 2-methyltetrahydrofuran, the halogenated hydrocarbon solvent is dichloromethane, and the alkyl nitrile solvent is acetonitrile.

[0096] (4) the Tinzaparin salt solid is dissolved in a trifluoroethanol / 2-methyltetrahydrofuran mixed solvent, and the solvent is volatilized at room temperature until a solid is precipitated, so that the Tinzaparin salt Type B is obtained; or In an embodiment of the application, the volume ratio of the trifluoroethanol / 2-methyltetrahydrofuran is 19:5.

[0097] (5) the Tinzaparin salt solid is dissolved in an alcohol solvent, and an ester, ether, ketone, aromatic hydrocarbon, halogenated hydrocarbon or alkyl nitrile solvent is added dropwise into the alcohol solvent under stirring until a solid is precipitated, so that the Tinzaparin salt Type B is obtained; or In an embodiment of the present application, the alcohol solvent is methanol or trifluoroethanol, the ester solvent is isopropyl acetate or ethyl acetate, the ether solvent is methylcyclohexyl ether or anisole, the ketone solvent is acetone, the aromatic hydrocarbon solvent is 4-isopropyltoluene or toluene, the halogenated hydrocarbon solvent is dibromomethane, and the alkyl nitrile solvent is acetonitrile.

[0098] (6) The solid of the tromethamine salt is dissolved in a sulfoxide solvent or an alcohol solvent, and then added to a ketone solvent, an ester solvent, an ether solvent, an aliphatic hydrocarbon solvent or a halogenated hydrocarbon solvent under stirring until a solid is precipitated, to obtain a tromethamine salt Type B.

[0099] In an embodiment of the present application, the sulfoxide solvent is dimethyl sulfoxide, the alcohol solvent is ethanol, the ketone solvent is methyl isobutyl ketone, the ester solvent is isopropyl acetate or isobutyl acetate, the ether solvent is isopropyl ether, the halogenated hydrocarbon solvent is 1,2-dichloroethane, and the aliphatic hydrocarbon solvent is n-heptane or cyclohexane.

[0100] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at diffraction angles 2θ of 5.4°±0.2°, 7.4°±0.2° and 16.0°±0.2°.

[0101] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at one or two or three of diffraction angles 2θ of 4.5°±0.2°, 11.5°±0.2° and 22.4°±0.2°.

[0102] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at diffraction angles 2θ of 4.5°±0.2°, 11.5°±0.2° and 22.4°±0.2°.

[0103] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at one or two or three of diffraction angles 2θ of 8.9°±0.2°, 19.8°±0.2° and 24.3°±0.2°.

[0104] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at diffraction angles 2θ of 8.9°±0.2°, 19.8°±0.2° and 24.3°±0.2°.

[0105] In one embodiment of the present application, the X-ray powder diffraction pattern of the Tinzaparin salt Type C has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2theta of 4.5°±0.2°, 5.4°±0.2°, 7.4°±0.2°, 8.9°±0.2°, 11.5°±0.2°, 16.0°±0.2°, 19.8°±0.2°, 22.4°±0.2°, 24.3°±0.2°.

[0106] In one embodiment of the present application, the X-ray powder diffraction pattern of the Tinzaparin salt Type C has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2theta of 4.5°±0.2°, 5.4°±0.2°, 7.4°±0.2°, 8.9°±0.2°, 11.5°±0.2°, 16.0°±0.2°, 19.8°±0.2°, 22.4°±0.2°, 24.3°±0.2°.

[0107] The present application provides a Tinzaparin salt Type C, wherein the molar ratio of S-indobufen to Tinzaparin is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0108] The present application provides a Tinzaparin salt Type C, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 19 .

[0109] When subjected to thermogravimetric analysis, the Tinzaparin salt Type C has a mass loss gradient of about 6.33±0.2% when heated to 120±2 °C, and its TGA is substantially as shown in Figure 20 .

[0110] When subjected to differential scanning calorimetry analysis, the Tinzaparin salt Type C has endothermic and exothermic peaks when heated to about 90±2 °C, and begins to melt when heated to about 155±2 °C, and its DSC is substantially as shown in Figure 21 .

[0111] The present application provides a method for preparing a Tinzaparin salt Type C, characterized in that, dissolving the Tinzaparin salt solid in an amide solvent, subjecting to vapor-liquid diffusion under an atmosphere of an ether, ester or halogenated hydrocarbon solvent until solid is precipitated, to obtain the Tinzaparin salt Type C.

[0112] In one embodiment of the present application, the amide solvent is N,N-dimethylacetamide or N-methylpyrrolidone, the ether solvent is diethyl ether, the ester solvent is ethyl acetate, and the halogenated hydrocarbon solvent is dichloromethane.

[0113] In an embodiment of the present application, the X-ray powder diffraction pattern of the aminitrozol salt Type D has characteristic peaks at diffraction angles 2q of 5.4°±0.2°, 7.5°±0.2°, 17.1°±0.2°.

[0114] In an embodiment of the present application, the X-ray powder diffraction pattern of the aminitrozol salt Type D has characteristic peaks at diffraction angles 2q of 4.5°±0.2°, 9.0°±0.2°, 24.7°±0.2°.

[0115] In an embodiment of the present application, the X-ray powder diffraction pattern of the aminitrozol salt Type D has characteristic peaks at diffraction angles 2q of 4.5°±0.2°, 9.0°±0.2°, 24.7°±0.2°.

[0116] In an embodiment of the present application, the X-ray powder diffraction pattern of the aminitrozol salt Type D has characteristic peaks at diffraction angles 2q of 18.5°±0.2°, 19.9°±0.2°, 22.8°±0.2°.

[0117] In an embodiment of the present application, the X-ray powder diffraction pattern of the aminitrozol salt Type D has characteristic peaks at diffraction angles 2q of 18.5°±0.2°, 19.9°±0.2°, 22.8°±0.2°.

[0118] In an embodiment of the present application, the X-ray powder diffraction pattern of the aminitrozol salt Type D has characteristic peaks at diffraction angles 2q of 4.5°±0.2°, 5.4°±0.2°, 7.5°±0.2°, 9.0°±0.2°, 17.1°±0.2°, 18.5°±0.2°, 19.9°±0.2°, 22.8°±0.2°, 24.7°±0.2°.

[0119] In an embodiment of the present application, the X-ray powder diffraction pattern of the aminitrozol salt Type D has characteristic peaks at diffraction angles 2q of 4.5°±0.2°, 5.4°±0.2°, 7.5°±0.2°, 9.0°±0.2°, 17.1°±0.2°, 18.5°±0.2°, 19.9°±0.2°, 22.8°±0.2°, 24.7°±0.2°.

[0120] The present application provides the tromethamine salt Type D, wherein the molar ratio of S-indobufen to tromethamine is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0121] The present application provides the tromethamine salt Type D, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 22

[0122] When performing thermal gravimetric analysis, the tromethamine salt Type D has a mass loss gradient of about 6.74±0.2% when heated to 120±2 °C, and its TGA is substantially as shown in Figure 23

[0123] When performing differential scanning calorimetric analysis, the tromethamine salt Type D has endothermic and exothermic peaks when heated to about 103±2 °C, has an exothermic peak when heated to about 133±2 °C, and starts to melt when heated to about 154±2 °C, and its DSC is substantially as shown in Figure 24

[0124] The present application provides a preparation method of the tromethamine salt Type D, characterized in that, The tromethamine salt solid is dissolved in tetrahydrofuran at high temperature, and then placed under low temperature conditions to precipitate a solid to obtain the tromethamine salt Type D.

[0125] In an embodiment of the present application, the high temperature is 80 °C; and the low temperature is -20 °C.

[0126] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type E has characteristic peaks at diffraction angles 2θ of 4.8°±0.2°, 10.2°±0.2°, and 14.4°±0.2°.

[0127] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type E has characteristic peaks at one or two or three of diffraction angles 2θ of 9.5°±0.2°, 15.9°±0.2°, and 19.4°±0.2°.

[0128] In an embodiment of the present application, the X-ray powder diffraction pattern of the tromethamine salt Type E has characteristic peaks at diffraction angles 2θ of 9.5°±0.2°, 15.9°±0.2°, and 19.4°±0.2°.

[0129] ​​​In one embodiment of the present application, the X-ray powder diffraction pattern of the Tinzaparin salt Type E has a characteristic peak at one or two or three of the diffraction angles 2-theta of 18.7° ± 0.2°, 19.8° ± 0.2°, 23.8° ± 0.2°.

[0130] In one embodiment of the present application, the X-ray powder diffraction pattern of the Tinzaparin salt Type E has a characteristic peak at one or two or three of the diffraction angles 2-theta of 18.7° ± 0.2°, 19.8° ± 0.2°, 23.8° ± 0.2°.

[0131] In one embodiment of the present application, the X-ray powder diffraction pattern of the Tinzaparin salt Type E has a characteristic peak at one or two or three of the diffraction angles 2-theta of 18.7° ± 0.2°, 19.8° ± 0.2°, 23.8° ± 0.2°.

[0132] In one embodiment of the present application, the X-ray powder diffraction pattern of the Tinzaparin salt Type E has a characteristic peak at one or two or three of the diffraction angles 2-theta of 18.7° ± 0.2°, 19.8° ± 0.2°, 23.8° ± 0.2°.

[0133] The present application provides a Tinzaparin salt Type E, wherein the molar ratio of S-indobufen to Tinzaparin is: 0.8 to 1.2, preferably 0.9 to 1.1, more preferably 1.

[0134] The present application provides a Tinzaparin salt Type E, characterized by an X-ray powder diffraction pattern substantially as shown in Figure 25 .

[0135] When subjected to thermogravimetric analysis, the Tinzaparin salt Type E has a mass loss gradient of about 1.18 ± 0.2% when heated to 120 ± 2ºC, and a TGA substantially as shown in Figure 26 .

[0136] When subjected to differential scanning calorimetry analysis, the Tinzaparin salt Type E starts to melt when heated to about 153 ± 2ºC, and a DSC substantially as shown in Figure 27 .

[0137] The preparation method of the thamide salt Type E provided by the present application is characterized in that, (1) dissolving the thamide salt solid in a mixed solvent system of trifluoroethanol and chloroform, and volatilizing the solvent at room temperature until the solid is precipitated to obtain the thamide salt Type E; or (2) dissolving the thamide salt solid in trifluoroethanol, and adding isopropyl ether dropwise into the solution under stirring until the solid is precipitated to obtain the thamide salt Type E.

[0138] In an embodiment of the present application, the X-ray powder diffraction spectrum of the urea co-crystal Type A has characteristic peaks at diffraction angles 2θ of 5.9°±0.2°, 12.7°±0.2°, and 14.3°±0.2°.

[0139] In an embodiment of the present application, the X-ray powder diffraction spectrum of the urea co-crystal Type A has characteristic peaks at one or two or three of diffraction angles 2θ of 17.5°±0.2°, 18.7°±0.2°, and 23.5°±0.2°.

[0140] In an embodiment of the present application, the X-ray powder diffraction spectrum of the urea co-crystal Type A has characteristic peaks at diffraction angles 2θ of 17.5°±0.2°, 18.7°±0.2°, and 23.5°±0.2°.

[0141] In an embodiment of the present application, the X-ray powder diffraction spectrum of the urea co-crystal Type A has characteristic peaks at one or two or three of diffraction angles 2θ of 20.3°±0.2°, 22.7°±0.2°, and 24.3°±0.2°.

[0142] In an embodiment of the present application, the X-ray powder diffraction spectrum of the urea co-crystal Type A has characteristic peaks at diffraction angles 2θ of 20.3°±0.2°, 22.7°±0.2°, and 24.3°±0.2°.

[0143] In an embodiment of the present application, the X-ray powder diffraction spectrum of the urea co-crystal Type A has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2θ of 5.9°±0.2°, 12.7°±0.2°, 14.3°±0.2°, 17.5°±0.2°, 18.7°±0.2°, 20.3°±0.2°, 22.7°±0.2°, 23.5°±0.2°, and 24.3°±0.2°.

[0144] In one embodiment of the application, the urea co-crystal Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2Θ of 5.9°±0.2°, 12.7°±0.2°, 14.3°±0.2°, 17.5°±0.2°, 18.7°±0.2°, 20.3°±0.2°, 22.7°±0.2°, 23.5°±0.2°, 24.3°±0.2°.

[0145] The present application provides a urea co-crystal Type A, wherein the molar ratio of S-indobufen to urea is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0146] The present application provides a urea co-crystal Type A, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 28

[0147] When subjected to thermogravimetric analysis, the urea co-crystal Type A has a mass loss gradient of about 0.26±0.2% when heated to 120±2ºC, and its TGA is substantially as shown in Figure 29

[0148] When subjected to differential scanning calorimetry analysis, the urea co-crystal Type A starts to melt at around 148±2ºC, and its DSC is substantially as shown in Figure 30

[0149] The present application provides a method for preparing a urea co-crystal Type A, characterized in that, The compound GP-046 in free form and urea are added to an acetone solvent system, and stirred at room temperature until the urea co-crystal Type A is obtained.

[0150] In one embodiment of the application, the potassium salt Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2Θ of 12.2°±0.2°, 14.5°±0.2°, 25.6°±0.2°.

[0151] In one embodiment of the application, the potassium salt Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2Θ of 15.2°±0.2°, 24.1°±0.2°, 24.6°±0.2°.

[0152] In one embodiment of the application, the potassium salt Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2Θ of 15.2°±0.2°, 24.1°±0.2°, 24.6°±0.2°.

[0153] ​​​In an embodiment of the present application, the X-ray powder diffraction pattern of the potassium salt Type A has characteristic peaks at diffraction angles 2-theta of 4.1°±0.2°, 20.4°±0.2°, 20.9°±0.2°.

[0154] In an embodiment of the present application, the X-ray powder diffraction pattern of the potassium salt Type A has characteristic peaks at diffraction angles 2-theta of 4.1°±0.2°, 20.4°±0.2°, 20.9°±0.2°.

[0155] In an embodiment of the present application, the X-ray powder diffraction pattern of the potassium salt Type A has characteristic peaks at diffraction angles 2-theta of 4.1°±0.2°, 12.2°±0.2°, 14.5°±0.2°, 15.2°±0.2°, 20.4°±0.2°, 20.9°±0.2°, 24.1°±0.2°, 24.6°±0.2°, 25.6°±0.2°.

[0156] In an embodiment of the present application, the X-ray powder diffraction pattern of the potassium salt Type A has characteristic peaks at diffraction angles 2-theta of 4.1°±0.2°, 12.2°±0.2°, 14.5°±0.2°, 15.2°±0.2°, 20.4°±0.2°, 20.9°±0.2°, 24.1°±0.2°, 24.6°±0.2°, 25.6°±0.2°.

[0157] The potassium salt Type A provided in the present application, wherein the molar ratio of S-indobufen to potassium ion is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0158] The potassium salt Type A provided in the present application, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 31 .

[0159] The potassium salt Type A has a mass loss gradient of about 4.76±0.2% when heated to 120±2ºC when subjected to thermogravimetric analysis, and its TGA is substantially as shown in Figure 32 .

[0160] The potassium salt Type A has endothermic peaks when heated to around 160±2ºC, endothermic and exothermic peaks when heated to around 199±2 and 202±2ºC, and begins to melt when heated to around 213±2ºC when subjected to differential scanning calorimetry analysis, and its DSC is substantially as shown in Figure 33 .

[0161] The application provides a preparation method of the potassium salt Type A, characterized in that, The compound GP-046 in free state is added to a potassium hydroxide-acetone solvent system, and stirred at room temperature until the potassium salt Type A is obtained.

[0162] In an embodiment of the application, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at diffraction angles 2θ of 5.2°±0.2°, 12.6°±0.2°, and 24.3°±0.2°.

[0163] In an embodiment of the application, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at one or two or three of diffraction angles 2θ of 6.5°±0.2°, 14.4°±0.2°, and 22.6°±0.2°.

[0164] In an embodiment of the application, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at diffraction angles 2θ of 6.5°±0.2°, 14.4°±0.2°, and 22.6°±0.2°.

[0165] In an embodiment of the application, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at one or two or three of diffraction angles 2θ of 4.2°±0.2°, 15.1°±0.2°, and 25.9°±0.2°.

[0166] In an embodiment of the application, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at diffraction angles 2θ of 4.2°±0.2°, 15.1°±0.2°, and 25.9°±0.2°.

[0167] In an embodiment of the application, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2θ of 4.2°±0.2°, 5.2°±0.2°, 6.5°±0.2°, 12.6°±0.2°, 14.4°±0.2°, 15.1°±0.2°, 22.6°±0.2°, 24.3°±0.2°, and 25.9°±0.2°.

[0168] In one embodiment of the present application, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at diffraction angles 2Q of 4.2°±0.2°, 5.2°±0.2°, 6.5°±0.2°, 12.6°±0.2°, 14.4°±0.2°, 15.1°±0.2°, 22.6°±0.2°, 24.3°±0.2°, 25.9°±0.2°.

[0169] The present application provides a potassium salt Type B, wherein the molar ratio of S-indobufen to potassium ions is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0170] The present application provides a potassium salt Type B, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 34

[0171] The present application provides a method for preparing a potassium salt Type B, characterized in that, The potassium salt Type A solid is heated to 160 °C after nitrogen purging to obtain the potassium salt Type B.

[0172] In one embodiment of the present application, the heating rate is 10 °C / min.

[0173] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type A has characteristic peaks at diffraction angles 2Q of 6.3°±0.2°, 9.6°±0.2°, 24.3°±0.2°.

[0174] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type A has characteristic peaks at one or two or three of diffraction angles 2Q of 6.6°±0.2°, 9.2°±0.2°, 12.7°±0.2°.

[0175] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type A has characteristic peaks at diffraction angles 2Q of 6.6°±0.2°, 9.2°±0.2°, 12.7°±0.2°.

[0176] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type A has characteristic peaks at one or two or three of diffraction angles 2Q of 5.3°±0.2°, 12.0°±0.2°, 25.6°±0.2°.

[0177] ​In one embodiment of the present application, the calcium salt Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 5.3°±0.2°, 12.0°±0.2°, 25.6°±0.2°.

[0178] In one embodiment of the present application, the calcium salt Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 5.3°±0.2°, 6.3°±0.2°, 6.6°±0.2°, 9.2°±0.2°, 9.6°±0.2°, 12.0°±0.2°, 12.7°±0.2°, 24.3°±0.2°, 25.6°±0.2°.

[0179] In one embodiment of the present application, the calcium salt Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 5.3°±0.2°, 6.3°±0.2°, 6.6°±0.2°, 9.2°±0.2°, 9.6°±0.2°, 12.0°±0.2°, 12.7°±0.2°, 24.3°±0.2°, 25.6°±0.2°.

[0180] The calcium salt Type A provided in the present application, wherein the molar ratio of S-indobufen to calcium ion is: 1.6~2.4, preferably 1.8~2.2, more preferably 2.

[0181] The calcium salt Type A provided in the present application, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 35 .

[0182] The calcium salt Type A provided in the present application, when subjected to thermogravimetric analysis, has a mass loss gradient of about 4.73±0.2% when heated to 150 ±2ºC, and its TGA is substantially as shown in Figure 36 .

[0183] The calcium salt Type A provided in the present application, when subjected to differential scanning calorimetry analysis, has an endothermic peak when heated to the vicinity of 150 ±2ºC, and endothermic and exothermic peaks when heated to the vicinity of 187±2 and 220±2ºC, and its DSC is substantially as shown in Figure 37 .

[0184] The method for preparing the calcium salt Type A provided in the present application, characterized in that, the compound GP-046 in free form and calcium hydroxide are added to an ethanol solvent system, and stirred at room temperature until the calcium salt Type A is obtained.

[0185] In one embodiment of the present application, the calcium salt Type B has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2q of 5.8°±0.2°, 18.1°±0.2°, 23.3°±0.2°.

[0186] In one embodiment of the present application, the calcium salt Type B has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2q of 10.6°±0.2°, 20.0°±0.2°.

[0187] In one embodiment of the present application, the calcium salt Type B has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2q of 10.6°±0.2°, 20.0°±0.2°.

[0188] In one embodiment of the present application, the calcium salt Type B has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2q of 5.8°±0.2°, 10.6°±0.2°, 18.1°±0.2°, 20.0°±0.2°, 23.3°±0.2°.

[0189] In one embodiment of the present application, the calcium salt Type B has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2q of 5.8°±0.2°, 10.6°±0.2°, 18.1°±0.2°, 20.0°±0.2°, 23.3°±0.2°.

[0190] The calcium salt Type B provided by the present application, wherein the molar ratio of S-indobufen to calcium ion is: 1.6~2.4, preferably 1.8~2.2, more preferably 2.

[0191] The calcium salt Type B provided by the present application, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 38 .

[0192] When subjected to thermogravimetric analysis, the calcium salt Type B has a mass loss gradient of about 2.69±0.2% when heated to 160±2 ºC, and a mass loss gradient of about 4.36±0.2% when heated to 300±2 ºC, and its TGA is substantially as shown in Figure 39 .

[0193] When subjected to differential scanning calorimetry analysis, the calcium salt Type B has an endothermic peak when heated to about 200±2ºC, and its DSC is substantially as shown in Figure 40 .

[0194] The method for preparing the calcium salt Type B provided by the present application, characterized in that, The compound GP-046 free form is added to a calcium hydroxide in acetonitrile solvent system, stirred at room temperature until the calcium salt Type B is obtained.

[0195] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at diffraction angles 2q of 11.6°±0.2°, 19.0°±0.2°, 24.9°±0.2°.

[0196] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at one or two or three of diffraction angles 2q of 14.3°±0.2°, 23.3°±0.2°, 26.5°±0.2°.

[0197] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at diffraction angles 2q of 14.3°±0.2°, 23.3°±0.2°, 26.5°±0.2°.

[0198] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at one or two or three of diffraction angles 2q of 21.1°±0.2°, 25.8°±0.2°, 27.4°±0.2°.

[0199] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at diffraction angles 2q of 21.1°±0.2°, 25.8°±0.2°, 27.4°±0.2°.

[0200] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2q of 11.6°±0.2°, 14.3°±0.2°, 19.0°±0.2°, 21.1°±0.2°, 23.3°±0.2°, 24.9°±0.2°, 25.8°±0.2°, 26.5°±0.2°, 27.4°±0.2°.

[0201] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at diffraction angles 2q of 11.6°±0.2°, 14.3°±0.2°, 19.0°±0.2°, 21.1°±0.2°, 23.3°±0.2°, 24.9°±0.2°, 25.8°±0.2°, 26.5°±0.2°, 27.4°±0.2°.

[0202] The calcium salt Type C according to the present application, wherein the molar ratio of S-indobufen to calcium ion is 1.6 to 2.4, preferably 1.8 to 2.2, more preferably 2.

[0203] The calcium salt Type C according to the present application, characterized by an X-ray powder diffraction pattern substantially as shown in Figure 41

[0204] The method for producing the calcium salt Type C according to the present application, characterized by, adding the compound GP-046 in free form and calcium hydroxide to a tetrahydrofuran / pure water mixed solvent system, and stirring at room temperature until the calcium salt Type C is obtained.

[0205] In one embodiment of the present application, the volume ratio of tetrahydrofuran / pure water is 19:1.

[0206] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type D has characteristic peaks at diffraction angles 2 theta of 5.7° ± 0.2°, 7.0° ± 0.2°, 8.3° ± 0.2°.

[0207] The calcium salt Type D according to the present application, wherein the molar ratio of S-indobufen to calcium ion is 1.6 to 2.4, preferably 1.8 to 2.2, more preferably 2.

[0208] The calcium salt Type D according to the present application, characterized by an X-ray powder diffraction pattern substantially as shown in Figure 42

[0209] When subjected to thermogravimetric analysis, the calcium salt Type D has a mass loss gradient of about 1.54 ± 0.2% when heated to 260 ± 2ºC, and its TGA is substantially as shown in Figure 43

[0210] When subjected to differential scanning calorimetry analysis, the calcium salt Type D starts to melt when heated to about 302 ± 2ºC, and its DSC is substantially as shown in Figure 44

[0211] The method for producing the calcium salt Type D according to the present application, characterized by, heating the calcium salt Type A solid to 240ºC to obtain the calcium salt Type D.

[0212] In one embodiment of the present application, the heating rate is 10ºC / min.

[0213] ​​​​In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 5.9°±0.2°, 8.9°±0.2°, 10.5°±0.2°.

[0214] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 5.3°±0.2°, 6.8°±0.2°, 26.5°±0.2°.

[0215] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 5.3°±0.2°, 6.8°±0.2°, 26.5°±0.2°.

[0216] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 11.8°±0.2°, 17.0°±0.2°, 17.9°±0.2°.

[0217] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 11.8°±0.2°, 17.0°±0.2°, 17.9°±0.2°.

[0218] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 5.3°±0.2°, 5.9°±0.2°, 6.8°±0.2°, 8.9°±0.2°, 10.5°±0.2°, 11.8°±0.2°, 17.0°±0.2°, 17.9°±0.2°, 26.5°±0.2°.

[0219] In one embodiment of the present application, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 5.3°±0.2°, 5.9°±0.2°, 6.8°±0.2°, 8.9°±0.2°, 10.5°±0.2°, 11.8°±0.2°, 17.0°±0.2°, 17.9°±0.2°, 26.5°±0.2°.

[0220] The present application provides a calcium salt Type E, wherein the molar ratio of S-indobufen to calcium ion is: 1.6~2.4, preferably 1.8~2.2, more preferably 2.

[0221] The calcium salt Type E provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 45

[0222] When subjected to thermal gravimetric analysis, the calcium salt Type E has a mass loss gradient of about 3.17±0.2% when heated to 130±2 ºC, and a mass loss gradient of about 3.49±0.2% when heated to 260±2 ºC, and its TGA is substantially as shown in Figure 46

[0223] When subjected to differential scanning calorimetric analysis, the calcium salt Type E has an endothermic peak when heated to about 148±2 ºC, an endothermic peak when heated to about 223±2 ºC, an endothermic peak and an exothermic peak when heated to about 254±2 ºC, and its DSC is substantially as shown in Figure 47

[0224] The method for preparing the calcium salt Type E provided by the present application is characterized in that, the compound GP-046 in free form and calcium hydroxide are added to an ethanol solvent system, and then stirred at room temperature and at 50 ºC, respectively, until the calcium salt Type E is obtained.

[0225] In an embodiment of the present application, the X-ray powder diffraction pattern of the magnesium salt Type A has characteristic peaks at diffraction angles 2θ of 5.1°±0.2°, 6.6°±0.2°, 13.1°±0.2°.

[0226] In an embodiment of the present application, the X-ray powder diffraction pattern of the magnesium salt Type A has characteristic peaks at one or two or three of diffraction angles 2θ of 9.8°±0.2°, 24.4°±0.2°, 24.8°±0.2°.

[0227] In an embodiment of the present application, the X-ray powder diffraction pattern of the magnesium salt Type A has characteristic peaks at diffraction angles 2θ of 9.8°±0.2°, 24.4°±0.2°, 24.8°±0.2°.

[0228] In an embodiment of the present application, the X-ray powder diffraction pattern of the magnesium salt Type A has characteristic peaks at any 4, or 5, or 6 of diffraction angles 2θ of 5.1°±0.2°, 6.6°±0.2°, 9.8°±0.2°, 13.1°±0.2°, 24.4°±0.2°, 24.8°±0.2°.

[0229] ​​​In one embodiment of the present application, the magnesium salt Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 5.1°±0.2°, 6.6°±0.2°, 9.8°±0.2°, 13.1°±0.2°, 24.4°±0.2°, 24.8°±0.2°.

[0230] The present application provides a magnesium salt Type A, wherein the molar ratio of S-indobufen to magnesium ion is: 1.6~2.4, preferably 1.8~2.2, more preferably 2.

[0231] The present application provides a magnesium salt Type A, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 48

[0232] When subjected to thermogravimetric analysis, the magnesium salt Type A has a mass loss gradient of about 8.83±0.2% when heated to 200±2 °C, and its TGA is substantially as shown in Figure 49

[0233] When subjected to differential scanning calorimetry analysis, the magnesium salt Type A has an endothermic peak when heated to about 187±2 °C, an endothermic peak and an exothermic peak when heated to about 200±2 °C, and begins to melt when heated to about 247±2 °C, and its DSC is substantially as shown in Figure 50

[0234] The present application provides a method for preparing a magnesium salt Type A, characterized in that, The free form of compound GP-046 and magnesium hydroxide are added to an ethanol solvent system, and stirred at room temperature until the magnesium salt Type A is obtained.

[0235] In one embodiment of the present application, the magnesium salt Type B has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 5.8°±0.2°, 7.2°±0.2°, 10.2°±0.2°.

[0236] In one embodiment of the present application, the magnesium salt Type B has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 6.8°±0.2°, 12.5°±0.2°, 25.1°±0.2°.

[0237] In one embodiment of the present application, the magnesium salt Type B has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 6.8°±0.2°, 12.5°±0.2°, 25.1°±0.2°.

[0238] ​​​In an embodiment of the present application, the X-ray powder diffraction pattern of the magnesium salt Type B has characteristic peaks at diffraction angles 2θ of 4.8°±0.2°, 23.4°±0.2°, 26.4°±0.2°.

[0239] In an embodiment of the present application, the X-ray powder diffraction pattern of the magnesium salt Type B has characteristic peaks at diffraction angles 2θ of 4.8°±0.2°, 23.4°±0.2°, 26.4°±0.2°.

[0240] In an embodiment of the present application, the X-ray powder diffraction pattern of the magnesium salt Type B has characteristic peaks at diffraction angles 2θ of 4.8°±0.2°, 5.8°±0.2°, 6.8°±0.2°, 7.2°±0.2°, 10.2°±0.2°, 12.5°±0.2°, 23.4°±0.2°, 25.1°±0.2°, 26.4°±0.2°.

[0241] In an embodiment of the present application, the X-ray powder diffraction pattern of the magnesium salt Type B has characteristic peaks at diffraction angles 2θ of 4.8°±0.2°, 5.8°±0.2°, 6.8°±0.2°, 7.2°±0.2°, 10.2°±0.2°, 12.5°±0.2°, 23.4°±0.2°, 25.1°±0.2°, 26.4°±0.2°.

[0242] The magnesium salt Type B provided by the present application, wherein the molar ratio of S-indobufen to magnesium ion is: 1.6~2.4, preferably 1.8~2.2, more preferably 2.

[0243] The magnesium salt Type B provided by the present application, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 51 .

[0244] The preparation method of the magnesium salt Type B provided by the present application, characterized in that, adding the compound GP-046 in free form and magnesium hydroxide to a tetrahydrofuran / pure water mixed solvent system, stirring at room temperature until the magnesium salt Type B is obtained.

[0245] In an embodiment of the present application, the volume ratio of tetrahydrofuran / pure water is 19:1.

[0246] In an embodiment of the application, the magnesium salt Type C has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 4.9°±0.2°, 7.0°±0.2°, 9.8°±0.2°.

[0247] In an embodiment of the application, the magnesium salt Type C has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 14.1°±0.2°, 26.6°±0.2°.

[0248] In an embodiment of the application, the magnesium salt Type C has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 14.1°±0.2°, 26.6°±0.2°.

[0249] In an embodiment of the application, the magnesium salt Type C has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 4.9°±0.2°, 7.0°±0.2°, 9.8°±0.2°, 14.1°±0.2°, 26.6°±0.2°.

[0250] In an embodiment of the application, the magnesium salt Type C has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 4.9°±0.2°, 7.0°±0.2°, 9.8°±0.2°, 14.1°±0.2°, 26.6°±0.2°.

[0251] The present application provides a magnesium salt Type C, wherein the molar ratio of S-indobufen to magnesium ions is: 1.6-2.4, preferably 1.8-2.2, more preferably 2.

[0252] The present application provides a magnesium salt Type C, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 52 .

[0253] The present application provides a method for preparing a magnesium salt Type C, characterized in that, heating the magnesium salt Type A solid to 220 °C to obtain the magnesium salt Type C.

[0254] In an embodiment of the application, the heating rate is 10 °C / min.

[0255] In an embodiment of the application, the ammonium salt Type A has an X-ray powder diffraction pattern with characteristic peaks at diffraction angles 2 theta of 4.2°±0.2°, 8.4°±0.2°, 12.6°±0.2°.

[0256] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at diffraction angles 2q of 15.3°±0.2°, 19.8°±0.2°, 24.3°±0.2°.

[0257] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at diffraction angles 2q of 15.3°±0.2°, 19.8°±0.2°, 24.3°±0.2°.

[0258] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at diffraction angles 2q of 14.6°±0.2°, 16.8°±0.2°, 25.4°±0.2°.

[0259] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at diffraction angles 2q of 14.6°±0.2°, 16.8°±0.2°, 25.4°±0.2°.

[0260] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at diffraction angles 2q of 4.2°±0.2°, 8.4°±0.2°, 12.6°±0.2°, 14.6°±0.2°, 15.3°±0.2°, 16.8°±0.2°, 19.8°±0.2°, 24.3°±0.2°, 25.4°±0.2°.

[0261] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at diffraction angles 2q of 4.2°±0.2°, 8.4°±0.2°, 12.6°±0.2°, 14.6°±0.2°, 15.3°±0.2°, 16.8°±0.2°, 19.8°±0.2°, 24.3°±0.2°, 25.4°±0.2°.

[0262] The ammonium salt Type A provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 53 .

[0263] The preparation method of the ammonium salt Type A provided by the present application is characterized in that, The compound GP-046 in free form and ammonia are added to a tetrahydrofuran / pure water mixed solvent system, and stirred at room temperature until the ammonium salt Type A is obtained.

[0264] In one embodiment of the present application, the volume ratio of tetrahydrofuran / pure water is 19:1.

[0265] In one embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2q of 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°.

[0266] In one embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2q of 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°.

[0267] In one embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2q of 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°.

[0268] In one embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2q of 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°.

[0269] In one embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2q of 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°.

[0270] In one embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2q of 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°.

[0271] In one embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2q of 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°.

[0272] The ammonium salt Type B provided by the present application, wherein the molar ratio of S-indobufen to ammonium ion is: 1.6-2.4, preferably 1.8-2.2, more preferably 2.

[0273] The ammonium salt Type B provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 54

[0274] When performing thermal gravimetric analysis, the ammonium salt Type B has a mass loss gradient of about 6.68±0.2% when heated to 150±2°C, and its TGA is substantially as shown in Figure 55

[0275] When performing differential scanning calorimetry analysis, the ammonium salt Type B has an endothermic peak when heated to about 139±2°C, and begins to melt when heated to about 197±2°C, and its DSC is substantially as shown in Figure 56

[0276] The preparation method of the ammonium salt Type B provided by the present application is characterized in that, The compound GP-046 in free form is added to an acetone solvent system with ammonia water, and stirred at room temperature until the ammonium salt Type B is obtained.

[0277] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type C has characteristic peaks at diffraction angles 2θ of 8.4°±0.2°, 14.8°±0.2°, and 19.6°±0.2°.

[0278] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type C has characteristic peaks at one or two or three of diffraction angles 2θ of 12.7°±0.2°, 24.1°±0.2°, and 26.6°±0.2°.

[0279] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type C has characteristic peaks at diffraction angles 2θ of 12.7°±0.2°, 24.1°±0.2°, and 26.6°±0.2°.

[0280] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type C has characteristic peaks at one or two or three of diffraction angles 2θ of 18.8°±0.2°, 22.7°±0.2°, and 26.0°±0.2°.

[0281] ​​​In one embodiment of the application, the X-ray powder diffraction pattern of the Ammonium Salt Type C has characteristic peaks at diffraction angles 2 theta of 18.8° ± 0.2°, 22.7° ± 0.2°, 26.0° ± 0.2°.

[0282] In one embodiment of the application, the X-ray powder diffraction pattern of the Ammonium Salt Type C has characteristic peaks at diffraction angles 2 theta of 8.4° ± 0.2°, 12.7° ± 0.2°, 14.8° ± 0.2°, 18.8° ± 0.2°, 19.6° ± 0.2°, 22.7° ± 0.2°, 24.1° ± 0.2°, 26.0° ± 0.2°, 26.6° ± 0.2°.

[0283] In one embodiment of the application, the X-ray powder diffraction pattern of the Ammonium Salt Type C has characteristic peaks at diffraction angles 2 theta of 8.4° ± 0.2°, 12.7° ± 0.2°, 14.8° ± 0.2°, 18.8° ± 0.2°, 19.6° ± 0.2°, 22.7° ± 0.2°, 24.1° ± 0.2°, 26.0° ± 0.2°, 26.6° ± 0.2°.

[0284] The Ammonium Salt Type C provided in the present application, wherein the molar ratio of S-indobufen to ammonium ion is: 1.5-1.7, preferably 1.6.

[0285] The Ammonium Salt Type C provided in the present application, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 57 .

[0286] When subjected to thermogravimetric analysis, the Ammonium Salt Type C has a mass loss gradient of about 8.60 ± 0.2% when heated to 150 ± 2ºC, its TGA being substantially as shown in Figure 58 .

[0287] When subjected to differential scanning calorimetry analysis, the Ammonium Salt Type C has an endothermic peak when heated to the vicinity of 137 ± 2ºC and starts to melt when heated to the vicinity of 198 ± 2ºC, its DSC being substantially as shown in Figure 59 .

[0288] The process for the preparation of the Ammonium Salt Type C provided in the present application, characterized in that, the compound GP-046 in free form is added to an acetonitrile solvent system with ammonia water, stirring at room temperature until the Ammonium Salt Type C is obtained.

[0289] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2q of 5.1°±0.2°, 8.8°±0.2°, 19.6°±0.2°.

[0290] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2q of 15.1°±0.2°, 18.9°±0.2°, 24.6°±0.2°.

[0291] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2q of 15.1°±0.2°, 18.9°±0.2°, 24.6°±0.2°.

[0292] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2q of 4.4°±0.2°, 13.3°±0.2°, 25.6°±0.2°.

[0293] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2q of 4.4°±0.2°, 13.3°±0.2°, 25.6°±0.2°.

[0294] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2q of 4.4°±0.2°, 5.1°±0.2°, 8.8°±0.2°, 13.3°±0.2°, 15.1°±0.2°, 18.9°±0.2°, 19.6°±0.2°, 24.6°±0.2°, 25.6°±0.2°.

[0295] In an embodiment of the present application, the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2q of 4.4°±0.2°, 5.1°±0.2°, 8.8°±0.2°, 13.3°±0.2°, 15.1°±0.2°, 18.9°±0.2°, 19.6°±0.2°, 24.6°±0.2°, 25.6°±0.2°.

[0296] The present application provides the ammonium salt Type D, wherein the molar ratio of S-indobufen to ammonium ion is: 4-6, preferably 5.

[0297] The ammonium salt Type D provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 60

[0298] When subjected to thermal gravimetric analysis, the ammonium salt Type D has a mass loss gradient of about 3.27±0.2% when heated to 150±2 ºC, its TGA being substantially as shown in Figure 61

[0299] When subjected to differential scanning calorimetry analysis, the ammonium salt Type D has an endothermic peak when heated to the vicinity of 132 ±2ºC and starts to melt when heated to the vicinity of 199±2 ºC, its DSC being substantially as shown in Figure 62

[0300] The method for preparing the ammonium salt Type D provided by the present application is characterized in that, The ammonium salt Type A solid is vacuum dried at 50 ºC until the ammonium salt Type D is obtained.

[0301] In an embodiment of the present application, the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at diffraction angles 2θ of 12.7°±0.2°, 16.4°±0.2°, 19.3°±0.2°.

[0302] In an embodiment of the present application, the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at one or two or three of the diffraction angles 2θ of 11.4°±0.2°, 15.2°±0.2°, 23.4°±0.2°.

[0303] In an embodiment of the present application, the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at the diffraction angles 2θ of 11.4°±0.2°, 15.2°±0.2°, 23.4°±0.2°.

[0304] In an embodiment of the present application, the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at one or two or three of the diffraction angles 2θ of 15.7°±0.2°, 20.2°±0.2°, 23.2°±0.2°.

[0305] In an embodiment of the present application, the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at the diffraction angles 2θ of 15.7°±0.2°, 20.2°±0.2°, 23.2°±0.2°.

[0306] ​​​In one embodiment of the present application, the X-ray powder diffraction pattern of the Choline Salt Type A has characteristic peaks at any 4 of, or 5 of, or 6 of, or 7 of, or 8 of, or 9 of the diffraction angles 2-theta of 11.4°±0.2°, 12.7°±0.2°, 15.2°±0.2°, 15.7°±0.2°, 16.4°±0.2°, 19.3°±0.2°, 20.2°±0.2°, 23.2°±0.2°, 23.4°±0.2°.

[0307] In one embodiment of the present application, the X-ray powder diffraction pattern of the Choline Salt Type A has characteristic peaks at any 4 of, or 5 of, or 6 of, or 7 of, or 8 of, or 9 of the diffraction angles 2-theta of 11.4°±0.2°, 12.7°±0.2°, 15.2°±0.2°, 15.7°±0.2°, 16.4°±0.2°, 19.3°±0.2°, 20.2°±0.2°, 23.2°±0.2°, 23.4°±0.2°.

[0308] In one embodiment of the present application, the X-ray powder diffraction pattern of the Choline Salt Type A has characteristic peaks at any 4 of, or 5 of, or 6 of, or 7 of, or 8 of, or 9 of the diffraction angles 2-theta of 11.4°±0.2°, 12.7°±0.2°, 15.2°±0.2°, 15.7°±0.2°, 16.4°±0.2°, 19.3°±0.2°, 20.2°±0.2°, 23.2°±0.2°, 23.4°±0.2°.

[0309] The Choline Salt Type A provided by the present application, wherein the molar ratio of S-indobufen to choline is: 0.8-1.2, preferably 0.9-1.1, more preferably 1. Figure 63 The Choline Salt Type A provided by the present application, wherein the X-ray powder diffraction pattern thereof is substantially as shown in

[0310] Figure 64 When subjected to thermogravimetric analysis, the Choline Salt Type A has a mass loss gradient of about 4.17±0.2% when heated to 120±2 °C, and the TGA thereof is substantially as shown in

[0311] When subjected to differential scanning calorimetric analysis, the Choline Salt Type A has an endothermic peak when heated to about 135±2 °C, and begins to melt when heated to about 214±2 °C, and the DSC thereof is substantially as shown in Figure 65

[0312] The preparation method of the Choline Salt Type A provided by the present application, wherein, The preparation method of the Choline Salt Type A provided by the present application, wherein,

[0313] In one embodiment of the present application, the X-ray powder diffraction pattern of the Lysine Salt Type A has characteristic peaks at the diffraction angles 2-theta of 5.5°±0.2°, 9.1°±0.2°, 10.1°±0.2°.

[0314] ​​In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type A has a characteristic peak at one or two or three of the diffraction angles 2-theta of 5.1°±0.2°, 21.3°±0.2°, 25.9°±0.2°.

[0315] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type A has a characteristic peak at one or two or three of the diffraction angles 2-theta of 5.1°±0.2°, 21.3°±0.2°, 25.9°±0.2°.

[0316] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type A has a characteristic peak at one or two or three of the diffraction angles 2-theta of 19.8°±0.2°, 22.2°±0.2°, 23.8°±0.2°.

[0317] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type A has a characteristic peak at one or two or three of the diffraction angles 2-theta of 19.8°±0.2°, 22.2°±0.2°, 23.8°±0.2°.

[0318] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type A has a characteristic peak at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2-theta of 5.1°±0.2°, 5.5°±0.2°, 9.1°±0.2°, 10.1°±0.2°, 19.8°±0.2°, 21.3°±0.2°, 22.2°±0.2°, 23.8°±0.2°, 25.9°±0.2°.

[0319] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type A has a characteristic peak at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2-theta of 5.1°±0.2°, 5.5°±0.2°, 9.1°±0.2°, 10.1°±0.2°, 19.8°±0.2°, 21.3°±0.2°, 22.2°±0.2°, 23.8°±0.2°, 25.9°±0.2°.

[0320] The present application provides a lysine salt Type A, wherein the molar ratio of S-indobufen to lysine is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0321] The present application provides a lysine salt Type A, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 66

[0322] ​When subjected to thermogravimetric analysis, the lysine salt Type A has a mass loss gradient of about 2.86 ± 0.2% when heated to 150 ± 2ºC, and a TGA substantially as shown in Figure 67

[0323] When subjected to differential scanning calorimetry analysis, the lysine salt Type A has an endothermic peak and an exothermic peak when heated to about 150 ± 2ºC, and begins to melt when heated to about 205 ± 2ºC, and a DSC substantially as shown in Figure 68

[0324] The present application provides a method for preparing the lysine salt Type A, characterized in that, The compound GP-046 in free form and lysine are added to an ethanol solvent system, and stirred at room temperature until the lysine salt Type A is obtained.

[0325] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type B has characteristic peaks at diffraction angles 2θ of 5.1° ± 0.2°, 6.1° ± 0.2°, 19.4° ± 0.2°.

[0326] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type B has characteristic peaks at one or two or three or four of diffraction angles 2θ of 7.0° ± 0.2°, 12.1° ± 0.2°, 21.2° ± 0.2°, 24.4° ± 0.2°.

[0327] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type B has characteristic peaks at diffraction angles 2θ of 7.0° ± 0.2°, 12.1° ± 0.2°, 21.2° ± 0.2°, 24.4° ± 0.2°.

[0328] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type B has characteristic peaks at any 4 or 5 or 6 or 7 of diffraction angles 2θ of 5.1° ± 0.2°, 6.1° ± 0.2°, 7.0° ± 0.2°, 12.1° ± 0.2°, 19.4° ± 0.2°, 21.2° ± 0.2°, 24.4° ± 0.2°.

[0329] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type B has characteristic peaks at diffraction angles 2θ of 5.1° ± 0.2°, 6.1° ± 0.2°, 7.0° ± 0.2°, 12.1° ± 0.2°, 19.4° ± 0.2°, 21.2° ± 0.2°, 24.4° ± 0.2°. ​​

[0330] The lysine salt Type B provided by the present application, wherein the molar ratio of S-indobufen to lysine is: 0.8-1.4, preferably 0.9-1.3, more preferably 1-1.25.

[0331] The lysine salt Type B provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 69

[0332] When subjected to thermogravimetric analysis, the lysine salt Type B has a mass loss gradient of about 7.69±0.2% when heated to 150±2 °C, and its TGA is substantially as shown in Figure 70

[0333] When subjected to differential scanning calorimetric analysis, the lysine salt Type B has an endothermic peak when heated to about 94 °C, an exothermic peak when heated to about 184±2 °C, and begins to melt when heated to about 210±2 °C, and its DSC is substantially as shown in Figure 71

[0334] The method for preparing the lysine salt Type B provided by the present application is characterized in that, the compound GP-046 in free form and lysine are added to a tetrahydrofuran / pure water mixed solvent system, and stirred at room temperature until the lysine salt Type B is obtained.

[0335] In an embodiment of the present application, the volume ratio of tetrahydrofuran / pure water is 19:1.

[0336] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2θ of 10.0°±0.2°, 16.8°±0.2°, and 23.6°±0.2°.

[0337] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at one or two or three of diffraction angles 2θ of 12.1°±0.2°, 20.1°±0.2°, and 24.9°±0.2°.

[0338] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2θ of 12.1°±0.2°, 20.1°±0.2°, and 24.9°±0.2°.

[0339] ​​​In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2q of 6.2°±0.2°, 16.1°±0.2°, 18.7°±0.2°.

[0340] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2q of 6.2°±0.2°, 16.1°±0.2°, 18.7°±0.2°.

[0341] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2q of 6.2°±0.2°, 10.0°±0.2°, 12.1°±0.2°, 16.1°±0.2°, 16.8°±0.2°, 18.7°±0.2°, 20.1°±0.2°, 23.6°±0.2°, 24.9°±0.2°.

[0342] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2q of 6.2°±0.2°, 10.0°±0.2°, 12.1°±0.2°, 16.1°±0.2°, 16.8°±0.2°, 18.7°±0.2°, 20.1°±0.2°, 23.6°±0.2°, 24.9°±0.2°.

[0343] The lysine salt Type C provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 72 .

[0344] The method for preparing the lysine salt Type C provided by the present application is characterized in that, heating the lysine salt Type B solid to 150 °C to obtain the lysine salt Type C.

[0345] In an embodiment of the present application, the heating rate is 10 °C / min.

[0346] In an embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2q of 6.9°±0.2°, 10.3°±0.2°, 21.8°±0.2°.

[0347] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2-theta of 5.0°±0.2°, 6.9°±0.2°, 10.3°±0.2°, 13.7°±0.2°, 17.2°±0.2°, 19.2°±0.2°, 20.4°±0.2°, 21.8°±0.2°, 24.7°±0.2°.

[0348] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2-theta of 5.0°±0.2°, 6.9°±0.2°, 10.3°±0.2°, 13.7°±0.2°, 17.2°±0.2°, 19.2°±0.2°, 20.4°±0.2°, 21.8°±0.2°, 24.7°±0.2°.

[0349] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2-theta of 5.0°±0.2°, 6.9°±0.2°, 10.3°±0.2°, 13.7°±0.2°, 17.2°±0.2°, 19.2°±0.2°, 20.4°±0.2°, 21.8°±0.2°, 24.7°±0.2°.

[0350] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2-theta of 5.0°±0.2°, 6.9°±0.2°, 10.3°±0.2°, 13.7°±0.2°, 17.2°±0.2°, 19.2°±0.2°, 20.4°±0.2°, 21.8°±0.2°, 24.7°±0.2°.

[0351] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2-theta of 5.0°±0.2°, 6.9°±0.2°, 10.3°±0.2°, 13.7°±0.2°, 17.2°±0.2°, 19.2°±0.2°, 20.4°±0.2°, 21.8°±0.2°, 24.7°±0.2°.

[0352] In one embodiment of the present application, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2-theta of 5.0°±0.2°, 6.9°±0.2°, 10.3°±0.2°, 13.7°±0.2°, 17.2°±0.2°, 19.2°±0.2°, 20.4°±0.2°, 21.8°±0.2°, 24.7°±0.2°.

[0353] The lysine salt Type D provided by the present application, wherein the molar ratio of S-indobufen to lysine is: 0.8~1.4, preferably 0.9~1.3, more preferably 1~1.25.

[0354] The lysine salt Type D provided by the present application, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 73

[0355] ​When subjected to thermal gravimetric analysis, lysine salt Type D has a mass loss gradient of about 4.11 ± 0.2% when heated to 150 ± 2 °C, and a TGA substantially as shown in FIG. 1. Figure 74

[0356] When subjected to differential scanning calorimetric analysis, lysine salt Type D begins to melt when heated to about 205 ± 2 °C, and a DSC substantially as shown in FIG. 2. Figure 75

[0357] The present application provides a method for preparing lysine salt Type D, characterized in that, adding compound GP-046 in free form and lysine to a tetrahydrofuran / pure water mixed solvent system, stirring at room temperature until solids precipitate; drying the solids at 50 °C under vacuum; and then heating the obtained solids to 175 °C to obtain lysine salt Type D.

[0358] In an embodiment of the present application, the volume ratio of tetrahydrofuran / pure water is 19:1.

[0359] In an embodiment of the present application, the time for drying at 50 °C under vacuum is about 3.5 hours.

[0360] In an embodiment of the present application, the heating rate is 10 °C / min.

[0361] In an embodiment of the present application, the X-ray powder diffraction pattern of betaine salt Type A has characteristic peaks at diffraction angles 2 theta of 10.1° ± 0.2°, 12.2° ± 0.2°, and 19.4° ± 0.2°.

[0362] In an embodiment of the present application, the X-ray powder diffraction pattern of betaine salt Type A has characteristic peaks at diffraction angles 2 theta of one or two or three of 14.8° ± 0.2°, 17.8° ± 0.2°, and 25.9° ± 0.2°.

[0363] In an embodiment of the present application, the X-ray powder diffraction pattern of betaine salt Type A has characteristic peaks at diffraction angles 2 theta of 14.8° ± 0.2°, 17.8° ± 0.2°, and 25.9° ± 0.2°.

[0364] In an embodiment of the present application, the X-ray powder diffraction pattern of betaine salt Type A has characteristic peaks at diffraction angles 2 theta of one or two or three of 19.9° ± 0.2°, 20.4° ± 0.2°, and 28.8° ± 0.2°.

[0365] ​​In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type A has characteristic peaks at diffraction angles 2q of 19.9°±0.2°, 20.4°±0.2°, 28.8°±0.2°.

[0366] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type A has characteristic peaks at diffraction angles 2q of 10.1°±0.2°, 12.2°±0.2°, 14.8°±0.2°, 17.8°±0.2°, 19.4°±0.2°, 19.9°±0.2°, 20.4°±0.2°, 25.9°±0.2°, 28.8°±0.2° at any 4, or 5, or 6, or 7, or 8, or 9 of them.

[0367] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type A has characteristic peaks at diffraction angles 2q of 10.1°±0.2°, 12.2°±0.2°, 14.8°±0.2°, 17.8°±0.2°, 19.4°±0.2°, 19.9°±0.2°, 20.4°±0.2°, 25.9°±0.2°, 28.8°±0.2°.

[0368] The present application provides a betaine salt Type A, wherein the molar ratio of S-indobufen to betaine is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0369] The present application provides a betaine salt Type A, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 76 .

[0370] The present application provides a method for preparing a betaine salt Type A, characterized in that, The compound GP-046 in free form and betaine are added to an acetone solvent system, and stirred at room temperature until the betaine salt Type A is obtained.

[0371] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2q of 6.6°±0.2°, 16.4°±0.2°, 22.7°±0.2°.

[0372] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2q of 7.1°±0.2°, 9.0°±0.2°, 11.5°±0.2° at one or two or three of them.

[0373] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2q of 7.1°±0.2°, 9.0°±0.2°, 11.5°±0.2°.

[0374] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2q of 10.0°±0.2°, 15.4°±0.2°, 23.6°±0.2°.

[0375] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2q of 10.0°±0.2°, 15.4°±0.2°, 23.6°±0.2°.

[0376] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2q of 6.6°±0.2°, 7.1°±0.2°, 9.0°±0.2°, 10.0°±0.2°, 11.5°±0.2°, 15.4°±0.2°, 16.4°±0.2°, 22.7°±0.2°, 23.6°±0.2°.

[0377] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2q of 6.6°±0.2°, 7.1°±0.2°, 9.0°±0.2°, 10.0°±0.2°, 11.5°±0.2°, 15.4°±0.2°, 16.4°±0.2°, 22.7°±0.2°, 23.6°±0.2°.

[0378] The betaine salt Type B provided by the present application, wherein the molar ratio of S-indobufen to betaine is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0379] The betaine salt Type B provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 77 .

[0380] The preparation method of the betaine salt Type B provided by the present application is characterized in that, The compound GP-046 in free form and betaine are added to an acetonitrile solvent system, and stirred at room temperature until the betaine salt Type B is obtained.

[0381] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2q of 6.8°±0.2°, 11.1°±0.2°, 19.4°±0.2°.

[0382] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2q of 4.7°±0.2°, 14.9°±0.2°, 25.0°±0.2°.

[0383] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2q of 4.7°±0.2°, 14.9°±0.2°, 25.0°±0.2°.

[0384] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2q of 17.0°±0.2°, 22.1°±0.2°, 26.1°±0.2°.

[0385] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2q of 17.0°±0.2°, 22.1°±0.2°, 26.1°±0.2°.

[0386] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2q of 4.7°±0.2°, 6.8°±0.2°, 11.1°±0.2°, 14.9°±0.2°, 17.0°±0.2°, 19.4°±0.2°, 22.1°±0.2°, 25.0°±0.2°, 26.1°±0.2°.

[0387] In an embodiment of the present application, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2q of 4.7°±0.2°, 6.8°±0.2°, 11.1°±0.2°, 14.9°±0.2°, 17.0°±0.2°, 19.4°±0.2°, 22.1°±0.2°, 25.0°±0.2°, 26.1°±0.2°.

[0388] The present application provides a betaine salt Type C, wherein the molar ratio of S-indobufen to betaine is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0389] The betaine salt Type C provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 78

[0390] When subjected to thermogravimetric analysis, the betaine salt Type C has a mass loss gradient of about 1.93±0.2% when heated to 120±2 ºC, and its TGA is substantially as shown in Figure 79

[0391] When subjected to differential scanning calorimetry analysis, the betaine salt Type C starts to melt when heated to about 147 ±2ºC, and its DSC is substantially as shown in Figure 80

[0392] The method for preparing the betaine salt Type C provided by the present application is characterized in that, vacuum drying the betaine salt Type B solid at 50 ºC until the betaine salt Type C is obtained.

[0393] In an embodiment of the present application, the X-ray powder diffraction pattern of the diethylamine salt Type A has characteristic peaks at diffraction angles 2θ of 6.3°±0.2°, 11.6°±0.2°, 12.7°±0.2°.

[0394] In an embodiment of the present application, the X-ray powder diffraction pattern of the diethylamine salt Type A has characteristic peaks at one or two or three of diffraction angles 2θ of 14.9°±0.2°, 18.5°±0.2°, 22.4°±0.2°.

[0395] In an embodiment of the present application, the X-ray powder diffraction pattern of the diethylamine salt Type A has characteristic peaks at diffraction angles 2θ of 14.9°±0.2°, 18.5°±0.2°, 22.4°±0.2°.

[0396] In an embodiment of the present application, the X-ray powder diffraction pattern of the diethylamine salt Type A has characteristic peaks at one or two or three of diffraction angles 2θ of 7.4°±0.2°, 17.1°±0.2°, 24.0°±0.2°.

[0397] In an embodiment of the present application, the X-ray powder diffraction pattern of the diethylamine salt Type A has characteristic peaks at diffraction angles 2θ of 7.4°±0.2°, 17.1°±0.2°, 24.0°±0.2°.

[0398] ​​​In an embodiment of the application, the diethylamine salt Type A has an X-ray powder diffraction pattern with characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the following diffraction angles 2-theta: 6.3°±0.2°, 7.4°±0.2°, 11.6°±0.2°, 12.7°±0.2°, 14.9°±0.2°, 17.1°±0.2°, 18.5°±0.2°, 22.4°±0.2°, 24.0°±0.2°.

[0399] In an embodiment of the application, the diethylamine salt Type A has an X-ray powder diffraction pattern with characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the following diffraction angles 2-theta: 6.3°±0.2°, 7.4°±0.2°, 11.6°±0.2°, 12.7°±0.2°, 14.9°±0.2°, 17.1°±0.2°, 18.5°±0.2°, 22.4°±0.2°, 24.0°±0.2°.

[0400] The diethylamine salt Type A according to the present application, wherein the molar ratio of S-indobufen to diethylamine is: 0.8 to 1.2, preferably 0.9 to 1.1, more preferably 1.

[0401] The diethylamine salt Type A according to the present application, characterized by an X-ray powder diffraction pattern substantially as shown in Figure 81 .

[0402] The diethylamine salt Type A according to the present application, when subjected to thermogravimetric analysis, has a mass loss gradient of about 13.83 ± 0.2% when heated to 125 ± 2ºC and a mass loss gradient of about 6.91 ± 0.2% when heated to 160 ± 2ºC, and a TGA substantially as shown in Figure 82 .

[0403] The diethylamine salt Type A according to the present application, when subjected to differential scanning calorimetry analysis, starts to melt around 163 ± 2ºC, and a DSC substantially as shown in Figure 83 .

[0404] The process for the preparation of the diethylamine salt Type A according to the present application, characterized by, adding the compound GP-046 in free form to diethylamine in an acetonitrile solvent system, stirring at room temperature until the diethylamine salt Type A is obtained.

[0405] In an embodiment of the application, the proline co-crystal Type A has an X-ray powder diffraction pattern with characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the following diffraction angles 2-theta: 5.6°±0.2°, 8.4°±0.2°, 20.3°±0.2°.

[0406] In one embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type A has characteristic peaks at diffraction angles 2q of 6.2°±0.2°, 7.4°±0.2°, 13.4°±0.2°.

[0407] In one embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type A has characteristic peaks at diffraction angles 2q of 6.2°±0.2°, 7.4°±0.2°, 13.4°±0.2°.

[0408] In one embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type A has characteristic peaks at diffraction angles 2q of 19.7°±0.2°, 22.2°±0.2°, 23.4°±0.2°.

[0409] In one embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type A has characteristic peaks at diffraction angles 2q of 19.7°±0.2°, 22.2°±0.2°, 23.4°±0.2°.

[0410] In one embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type A has characteristic peaks at diffraction angles 2q of 5.6°±0.2°, 6.2°±0.2°, 7.4°±0.2°, 8.4°±0.2°, 13.4°±0.2°, 19.7°±0.2°, 20.3°±0.2°, 22.2°±0.2°, 23.4°±0.2°.

[0411] In one embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type A has characteristic peaks at diffraction angles 2q of 5.6°±0.2°, 6.2°±0.2°, 7.4°±0.2°, 8.4°±0.2°, 13.4°±0.2°, 19.7°±0.2°, 20.3°±0.2°, 22.2°±0.2°, 23.4°±0.2°.

[0412] The present application provides a proline co-crystal Type B, wherein the molar ratio of S-indobufen to the proline co-crystal is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0413] The present application provides a proline co-crystal Type A, characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 84

[0414] ​When subjected to thermogravimetric analysis, proline co-crystal Type A has a mass loss gradient of about 0.10 ± 0.2% when heated to 120 ± 2ºC, its TGA is substantially as shown in Figure 85

[0415] When subjected to differential scanning calorimetry analysis, proline co-crystal Type A starts to melt when heated to around 169 ± 2ºC, its DSC is substantially as shown in Figure 86

[0416] The present application provides a method for preparing proline co-crystal Type A, characterized in that, adding compound GP-046 in free form and proline to an acetonitrile solvent system, stirring at room temperature until proline co-crystal Type A is obtained.

[0417] In an embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type B has characteristic peaks at diffraction angles 2θ of 5.1° ± 0.2°, 18.1° ± 0.2°, 19.6° ± 0.2°.

[0418] In an embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type B has characteristic peaks at diffraction angles 2θ of one or two or three of 15.2° ± 0.2°, 19.0° ± 0.2°, 25.7° ± 0.2°.

[0419] In an embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type B has characteristic peaks at diffraction angles 2θ of 15.2° ± 0.2°, 19.0° ± 0.2°, 25.7° ± 0.2°.

[0420] In an embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type B has characteristic peaks at diffraction angles 2θ of one or two or three of 10.2° ± 0.2°, 24.2° ± 0.2°, 24.9° ± 0.2°.

[0421] In an embodiment of the present application, the X-ray powder diffraction pattern of the proline co-crystal Type B has characteristic peaks at diffraction angles 2θ of 10.2° ± 0.2°, 24.2° ± 0.2°, 24.9° ± 0.2°.

[0422] ​​In one embodiment of the present application, the X-ray powder diffraction pattern of the Proline Co-crystal Type B has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2-theta of 5.1°±0.2°, 10.2°±0.2°, 15.2°±0.2°, 18.1°±0.2°, 19.0°±0.2°, 19.6°±0.2°, 24.2°±0.2°, 24.9°±0.2°, 25.7°±0.2°.

[0423] In one embodiment of the present application, the X-ray powder diffraction pattern of the Proline Co-crystal Type B has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2-theta of 5.1°±0.2°, 10.2°±0.2°, 15.2°±0.2°, 18.1°±0.2°, 19.0°±0.2°, 19.6°±0.2°, 24.2°±0.2°, 24.9°±0.2°, 25.7°±0.2°.

[0424] The Proline Co-crystal Type B provided by the present application, wherein the molar ratio of S-indobufen to the Proline Co-crystal is: 0.8-1.2, preferably 0.9-1.1, more preferably 1.

[0425] The Proline Co-crystal Type B provided by the present application is characterized in that its X-ray powder diffraction pattern is substantially as shown in Figure 87

[0426] The preparation method of the Proline Co-crystal Type B provided by the present application is characterized in that, The Proline Co-crystal Type A is subjected to DVS test to obtain the Proline Co-crystal Type B.

[0427] In one embodiment of the present application, the procedure of the DVS test is: 0%RH-95%RH-0%RH.

[0428] In one embodiment of the present application, the X-ray powder diffraction pattern of the Hexadecylamine salt Type A has characteristic peaks at the diffraction angles 2-theta of 4.9°±0.2°, 8.3°±0.2°, 12.1°±0.2°.

[0429] In one embodiment of the present application, the X-ray powder diffraction pattern of the Hexadecylamine salt Type A has characteristic peaks at one or two or three of the diffraction angles 2-theta of 9.8°±0.2°, 14.8°±0.2°, 20.9°±0.2°.

[0430] ​In an embodiment of the present application, the X-ray powder diffraction pattern of the hexadecylamine salt Type A has characteristic peaks at diffraction angles 2q of 9.8°±0.2°, 14.8°±0.2°, 20.9°±0.2°.

[0431] In an embodiment of the present application, the X-ray powder diffraction pattern of the hexadecylamine salt Type A has characteristic peaks at diffraction angles 2q of 5.6°±0.2°, 7.4°±0.2°, 22.3°±0.2°.

[0432] In an embodiment of the present application, the X-ray powder diffraction pattern of the hexadecylamine salt Type A has characteristic peaks at diffraction angles 2q of 5.6°±0.2°, 7.4°±0.2°, 22.3°±0.2°.

[0433] In an embodiment of the present application, the X-ray powder diffraction pattern of the hexadecylamine salt Type A has characteristic peaks at diffraction angles 2q of 4.9°±0.2°, 5.6°±0.2°, 7.4°±0.2°, 8.3°±0.2°, 9.8°±0.2°, 12.1°±0.2°, 14.8°±0.2°, 20.9°±0.2°, 22.3°±0.2°.

[0434] In an embodiment of the present application, the X-ray powder diffraction pattern of the hexadecylamine salt Type A has characteristic peaks at diffraction angles 2q of 4.9°±0.2°, 5.6°±0.2°, 7.4°±0.2°, 8.3°±0.2°, 9.8°±0.2°, 12.1°±0.2°, 14.8°±0.2°, 20.9°±0.2°, 22.3°±0.2°.

[0435] The hexadecylamine salt Type A provided herein has a molar ratio of S-indobufen to hexadecylamine of 1.6 to 2.4, preferably 1.8 to 2.2, more preferably 2.

[0436] The hexadecylamine salt Type A provided herein has an X-ray powder diffraction pattern substantially as shown in Figure 88 .

[0437] The hexadecylamine salt Type A provided herein has a TGA substantially as shown in Figure 89 .

[0438] When differential scanning calorimetry analysis is performed, the hexadecylamine salt Type A has an endothermic peak when heated to the vicinity of 64 ± 2ºC and starts to melt when heated to the vicinity of 169 ± 2ºC, and the DSC thereof is substantially as shown in Figure 90

[0439] The present application provides a method for preparing the hexadecylamine salt Type A, characterized in that, The compound GP-046 in free form and hexadecylamine are added to an acetone solvent system, and stirred at room temperature until the hexadecylamine salt Type A is obtained.

[0440] The present application also discloses a pharmaceutical composition, the S-indobufen salt described above, and one or more pharmaceutically acceptable carriers.

[0441] The present application also discloses the use of the S-indobufen salt described above in the preparation of a drug for preventing and / or treating anti-platelet diseases.

[0442] Further, the disease is an ischemic cardiovascular lesion caused by arteriosclerosis, an ischemic cerebrovascular lesion, venous thrombosis, or thrombosis prevention when hemodialysis is performed.

[0443] In the present application, the X-ray powder diffraction pattern is obtained using Cu-Kα radiation.

[0444] The term "pharmaceutically acceptable carrier" as used herein refers to a diluent, adjuvant, excipient, or vehicle with which a therapeutic agent is administered, and which is within the scope of sound medical judgment to contact the tissues of human beings and / or other animals without excessive toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit / risk ratio.

[0445] The compositions of the present application can act systemically and / or topically. To this end, they can be administered by suitable routes, for example by injection, intravenously, intra-arterially, subcutaneously, intraperitoneally, intramuscularly or transdermally; or orally, buccally, nasally, transmucosally, topically, in the form of ophthalmic preparations or by inhalation.

[0446] For these administration routes, the compositions of the present application can be administered in suitable dosage forms.

[0447] The dosage forms can be solid preparations, semi-solid preparations, liquid preparations or gaseous preparations, specifically including but not limited to tablets, capsules, powders, granules, lozenges, hard candies, powders, sprays, creams, ointments, suppositories, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, suspensions, elixirs, syrups.

[0448] ​The pharmaceutical compositions described herein can be prepared by any method known to the art, for example, by means of mixing, dissolving, granulating, sugar coating, milling, emulsifying, re- lyophilizing, and so on.

[0449] The term "therapeutically effective amount" as used herein refers to the amount of S-indobufen salt that, upon administration, will relieve to some extent one or more of the symptoms of the disorder being treated.

[0450] Dosage regimens can be adjusted to provide the optimum desired response. For example, a single bolus can be administered, several divided doses can be administered over time or the dose can be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It is to be noted that dosage values can vary with the type and severity of the condition to be alleviated. It is to be further understood that for any particular individual, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that the dosage ranges set forth above are exemplary.

[0451] "Individual" as used herein includes a human or non-human animal. Exemplary human individuals include a human individual (referred to as a patient) suffering from a disease (e.g., a disease described herein) or a normal individual. "Non-human animals" in the present application include all vertebrates, e.g., non-mammals (e.g., birds, amphibians, reptiles) and mammals, e.g., non-human primates, domestic animals, and / or laboratory animals (e.g., sheep, dog, cat, cow, pig, etc.).

[0452] The S-indobufen salt of the present application has excellent solubility, especially in FaSSIF and water, excellent compressibility and stability, low hygroscopicity, very uniform particle size distribution, and low adhesion, and has unique advantages in formulation and application. BRIEF DESCRIPTION OF DRAWINGS

[0453] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required to be used in the embodiments will be briefly introduced as follows. It should be understood that the following drawings only show some of the embodiments of the present application, and therefore should not be considered as a limitation on the scope. For those skilled in the art, other related drawings can also be obtained without creative labor on the basis of these drawings.

[0454] Figure 1 XRPD pattern of meglumine salt Type A; Figure 2 TGA pattern of meglumine salt Type A; Figure 3 DSC pattern of meglumine salt Type A; Figure 4 XRPD pattern of meglumine salt Type B; Figure 5TGA pattern of meglumine salt Type B; Figure 6 DSC pattern of meglumine salt Type B; Figure 7 XRPD pattern of meglumine salt Type D; Figure 8 TGA pattern of meglumine salt Type D; Figure 9 DSC pattern of meglumine salt Type D; Figure 10 XRPD pattern of meglumine salt Type E; Figure 11 TGA pattern of meglumine salt Type E; Figure 12 DSC pattern of meglumine salt Type E; Figure 13 XRPD pattern of tromethamine salt Type A; Figure 14 TGA pattern of tromethamine salt Type A; Figure 15 DSC pattern of tromethamine salt Type A; Figure 16 XRPD pattern of tromethamine salt Type B; Figure 17 TGA pattern of tromethamine salt Type B; Figure 18 DSC pattern of tromethamine salt Type B; Figure 19 XRPD pattern of tromethamine salt Type C; Figure 20 TGA pattern of tromethamine salt Type C; Figure 21 DSC pattern of tromethamine salt Type C; Figure 22 XRPD pattern of tromethamine salt Type D; Figure 23 TGA pattern of tromethamine salt Type D; Figure 24 DSC pattern of tromethamine salt Type D; Figure 25 XRPD pattern of tromethamine salt Type E; Figure 26 TGA pattern of tromethamine salt Type E; Figure 27 DSC pattern of tromethamine salt Type E; Figure 28 XRPD pattern of Urea co-crystal Type A; Figure 29 TGA pattern of Urea co-crystal Type A; Figure 30 DSC pattern of Urea co-crystal Type A; Figure 31 XRPD pattern of Potassium salt Type A; Figure 32 TGA pattern of Potassium salt Type A; Figure 33 DSC pattern of Potassium salt Type A; Figure 34 XRPD pattern of Potassium salt Type B; Figure 35 XRPD pattern of Calcium salt Type A; Figure 36 TGA pattern of Calcium salt Type A; Figure 37 DSC pattern of Calcium salt Type A; Figure 38 XRPD pattern of Calcium salt Type B; Figure 39 TGA pattern of Calcium salt Type B; Figure 40 DSC pattern of Calcium salt Type B; Figure 41 XRPD pattern of Calcium salt Type C; Figure 42 XRPD pattern of Calcium salt Type D; Figure 43 TGA pattern of Calcium salt Type D; Figure 44 DSC pattern of Calcium salt Type D; Figure 45 XRPD pattern of Calcium salt Type E; Figure 46 TGA pattern of Calcium salt Type E; Figure 47 DSC pattern of Calcium salt Type E; Figure 48 XRPD pattern of Magnesium salt Type A; Figure 49 TGA pattern of Magnesium salt Type A; Figure 50 DSC pattern of Magnesium salt Type A; Figure 51 XRPD pattern of Magnesium salt Type B; Figure 52 XRPD pattern of Magnesium salt Type C; Figure 53 XRPD pattern of Ammonium salt Type A; Figure 54 XRPD pattern of Ammonium salt Type B; Figure 55 TGA pattern of Ammonium salt Type B; Figure 56 DSC pattern of Ammonium salt Type B; Figure 57 XRPD pattern of Ammonium salt Type C; Figure 58 TGA pattern of Ammonium salt Type C; Figure 59 DSC pattern of Ammonium salt Type C; Figure 60 XRPD pattern of Ammonium salt Type D; Figure 61 TGA pattern of Ammonium salt Type D; Figure 62 DSC pattern of Ammonium salt Type D; Figure 63 XRPD pattern of Choline salt Type A; Figure 64 TGA pattern of Choline salt Type A; Figure 65 DSC pattern of Choline salt Type A; Figure 66 XRPD pattern of Lysine salt Type A; Figure 67 TGA pattern of Lysine salt Type A; Figure 68 DSC pattern of Lysine salt Type A; Figure 69 XRPD pattern of Lysine salt Type B; Figure 70 TGA pattern of Lysine salt Type B; Figure 71 DSC pattern of Lysine salt Type B; Figure 72 XRPD pattern of Lysine salt Type C; Figure 73 XRPD pattern of Lysine salt Type D; Figure 74 TGA pattern of Lysine salt Type D; Figure 75DSC plot of Lysine salt Type D; Figure 76 XRPD plot of Betaine salt Type A; Figure 77 XRPD plot of Betaine salt Type B; Figure 78 XRPD plot of Betaine salt Type C; Figure 79 TGA plot of Betaine salt Type C; Figure 80 DSC plot of Betaine salt Type C; Figure 81 XRPD plot of Diethylamine salt Type A; Figure 82 TGA plot of Diethylamine salt Type A; Figure 83 DSC plot of Diethylamine salt Type A; Figure 84 XRPD plot of Proline co-crystal Type A; Figure 85 TGA plot of Proline co-crystal Type A; Figure 86 DSC plot of Proline co-crystal Type A; Figure 87 XRPD plot of Proline co-crystal Type B; Figure 88 XRPD plot of Hexadecylamine salt Type A; Figure 89 TGA plot of Hexadecylamine salt Type A; Figure 90 DSC plot of Hexadecylamine salt Type A; Figure 91 Solubility curves of different crystalline forms in FaSSIF; Figure 92 Solubility curves of different crystalline forms in pure water; Figure 93 XRPD overlay of stability of Potassium salt Type A; Figure 94 XRPD overlay of stability of Methylglucamine salt Type A; Figure 95 XRPD overlay of stability of Tromethamine salt Type B; Figure 96 XRPD overlay of stability of Urea co-crystal Type A; Figure 97 XRPD overlay of stability of Tromethamine salt Type E; Figure 98 DVS plot of Form C in free form; Figure 99 DVS plot of Titrated B; Figure 100 DVS plot of MeGlucinate Type E; Figure 101 DVS plot of Urea Co-Crystal Type A; Figure 102 Particle size distribution plot of Potassium Salt Type A; Figure 103 Particle size distribution plot of MeGlucinate Type A; Figure 104 Particle size distribution plot of Proline Co-Crystal Type A; Figure 105 Particle size distribution plot of Urea Co-Crystal Type A; Figure 106 Particle size distribution plot of Titrated E; Figure 107 Particle size distribution plot of Form C in free form; Figure 108 Particle size distribution plot of MeGlucinate Type A 1 H NMR plot; Figure 109: MeGlucinate Type B 1 H NMR plot; Figure 110: MeGlucinate Type D 1 H NMR plot; Figure 111: MeGlucinate Type E 1 H NMR plot; Figure 112 H NMR plot of Titrated B; 1 H NMR plot; Figure 113 H NMR plot of Urea Co-Crystal Type A; 1 H NMR plot; Figure 114 H NMR plot of Potassium Salt Type A; 1 H NMR plot; Figure 115 H NMR plot of Potassium Salt Type B; 1 H NMR plot; Figure 116 H NMR plot of Calcium Salt Type B; 1 H NMR plot; Figure 117 H NMR plot of Calcium Salt Type D; 1 H NMR plot; Figure 118 Calcium salts of Type E 1 H NMR spectrum; Figure 119 Magnesium salt Type A 1 H NMR spectrum; Figure 120 Ammonium salt Type B 1 H NMR spectrum; Figure 121 Ammonium salts of Type C 1 H NMR spectrum; Figure 122 Ammonium salt Type D 1 H NMR spectrum; Figure 123 Choline salts Type A 1 H NMR spectrum; Figure 124 Lysine salt Type A 1 H NMR spectrum; Figure 125 Lysine salt Type B 1 H NMR spectrum; Figure 126 Lysine salt Type D 1 H NMR spectrum; Figure 127 Type C betaine salt 1 H NMR spectrum; Figure 128 Type A diethylamine salt 1 H NMR spectrum; Figure 129 Proline cocrystal Type A 1 H NMR spectrum; Figure 130 Type A hexadecylamine salt 1 H NMR spectrum. Detailed Implementation

[0455] According to the present invention, the compound of formula (I) used as a raw material refers to its solid (crystalline or amorphous), semi-solid, wax, or oil form. Preferably, the compound of formula (I) used as a raw material is in solid powder form. The "stirring" is performed by conventional methods in the art, such as magnetic stirring or mechanical stirring, at a stirring speed of 50 to 1800 rpm, wherein magnetic stirring is 200 to 1500 rpm, preferably 300 to 1000 rpm, and mechanical stirring is preferably 100 to 300 rpm.

[0456] In the present application, "crystal" or "polymorph" refers to that which is characterized by the X-ray diffraction pattern shown. Those skilled in the art will appreciate that the physicochemical properties discussed herein can be characterized with experimental error that depends on the conditions of the instrument, the preparation of the sample, and the purity of the sample. In particular, it is well known in the art that X-ray diffraction patterns can vary with the conditions of the instrument. In particular, it is noted that the relative intensities of the X-ray diffraction pattern can vary with experimental conditions, and therefore the order of peak intensities cannot be used as the sole or determining factor. In fact, the relative intensities of the diffraction peaks in an X-ray diffraction pattern are related to the preferred orientation of the crystal, and the peak intensities shown herein are illustrative and not intended for absolute comparison. In addition, the experimental error in peak angles is typically 5% or less, and this error in angles should be taken into account, typically allowing for a ± 0.2° error. In addition, there can be a general shift in peak angles due to experimental factors such as sample thickness, and some shift is typically allowed. Thus, those skilled in the art will appreciate that the X-ray diffraction pattern of a crystal form of the present application need not be identical to the X-ray diffraction pattern shown in the examples herein, and that "X-ray diffraction pattern identical" does not mean absolutely identical, but that the peak positions can differ by ± 0.2° and that the peak intensities allow for some variability. Any crystal form having a pattern with peaks identical or similar to those in these patterns is within the scope of the present application. Those skilled in the art can compare the patterns listed herein with the pattern of an unknown crystal form to determine whether the two sets of patterns reflect the same or different crystal forms.

[0457] In some embodiments, the crystal forms of the present application are pure, single, substantially free of any other crystal form. In the present application, "substantially free of" when used in reference to a new crystal form indicates that the crystal form contains less than about 20% by weight of another crystal form, more preferably less than about 10% by weight of another crystal form, more preferably less than about 5% by weight of another crystal form, and more preferably less than about 1% by weight of another crystal form. It is to be understood that the values and ranges of values recited in the present application are meant to be illustrative and not limiting, and that any numerical value can be modified by the use of a "more or less" qualifier together with the term "about," to describe a variation of the numerical value. Thus, for example, "about 20%" can be interpreted to mean "more or less than about 20%."

[0458] The upper and lower limits of the ranges of values recited in the present application can be combined to form ranges also recited in the present application.

[0459] In this document, the term "comprising" is to be read as open-ended, that is, as including the listed steps as well as other steps.

[0460] In the present invention, the term "essentially as shown in Figure X" means that the exact position and intensity of the peaks in the figures should not be interpreted as absolute values. For example, the 2-theta values of the X-ray powder diffraction patterns can be subject to errors due to different measurement conditions (such as the equipment and instrument used) and different samples, and the measurement error of the diffraction angle of the X-ray powder diffraction pattern is 5% or less, and in general, a difference of ±0.2° of a given value is considered appropriate. It should also be understood that the relative intensity of the peaks can fluctuate with experimental conditions and sample preparation such as the preferred orientation of the particles in the sample. The use of automatic or fixed divergence slits can also affect the calculation of the relative intensity. The intensities shown in the X-ray powder diffraction patterns included herein are only exemplary and cannot be used for absolute comparison. Of course, "essentially as shown in Figure X" itself includes the meaning of "as shown in Figure X".

[0461] The present invention will be further described by way of specific examples, but not for limiting the scope of protection of the present invention. Those skilled in the art can make improvements to the preparation method and use the instrument within the scope of the claims, and these improvements should also be considered as the scope of protection of the present invention. Therefore, the scope of protection of the patent of the present invention should be subject to the appended claims.

[0462] The abbreviations used in the present invention are explained as follows: XRPD: X-ray powder diffraction DSC: differential scanning calorimetry TGA: thermogravimetric analysis DVS: dynamic vapor sorption PSD: particle size distribution UPLC: ultra-performance liquid chromatography The X-ray powder diffraction patterns described in the present invention are collected on a PANalytical Empyrean or X'Pert Pro X-ray powder diffractometer. 3 The method parameters of the X-ray powder diffraction described in the present invention are as follows: X-ray source: Cu, Kα Kα1 (Å): 1.54060; Kα2 (Å): 1.54439 Kα2 / Kα1 intensity ratio: 0.50 Voltage: 45 kilovolts (kV) Current: 40 milliamps (mA) Divergence slit: 1 / 8 degree Scan mode: continuous scan Scan range: from 3.0 to 40.0 degrees Scan step: 0.0263 degrees Scan time per step: 46.67 degrees Scan time: about 5 minutes The differential scanning calorimetry (DSC) plots described herein were collected on a TA Discovery 2500. The method parameters for the differential scanning calorimetry (DSC) described herein are as follows: Method: Linear temperature ramp Sample pan: Aluminum pan, open Temperature range: Room temperature to 250 °C Scan rate: 10 °C / minute Protective gas: N2 The thermogravimetric analysis (TGA) plots described herein were collected on a TA Discovery 5500. The method parameters for the thermogravimetric analysis (TGA) described herein are as follows: Method: Linear temperature ramp Sample pan: Aluminum pan, crimped Temperature range: Room temperature to 200 °C Scan rate: 10 °C / minute Protective gas: N2 The dynamic moisture sorption plots described herein were collected on a SMS DVS Intrinsic. The method parameters for the dynamic moisture sorption described herein are as follows: Temperature: 25 °C Sample size: 20 to 40 milligrams Protective gas and flow rate: N2, 200 milliliters / minute Maximum mass change dm / dt at equilibrium: 0.002% / minute Minimum dm / dt equilibration time: 10 minutes Maximum equilibration time: 180 minutes Humidity range: 0% RH to 95% RH to 0% RH Humidity change gradient: 10% RH (between 0% RH and 90% RH), 5% RH (between 90% RH and 95% RH) The particle size distribution results described herein were collected on a Microtrac S3500 laser particle size analyzer. The Microtrac S3500 is equipped with an SDC (Sample Delivery Controller) sample delivery system. The test was performed using the wet method, and the test dispersion medium was Isopar G (containing 0.2% lecithin). The method parameters for the laser particle size analyzer are as follows:

[0463] : Flow rate 60% of 65 mL / s The UPLC purity data in this application were collected on a Waters H-Class with a diode array detector (DAD). The HPLC method parameters for testing purity described in this application are as follows: 1. Column: Xterra MS C18, 4.6 mm x 50 mm, 2.5 μm 2. Mobile phase: A: 10 mM KH2PO4 in H2O (pH = 4.0) B: Acetonitrile The elution gradient is as follows:

[0464] 3. Flow rate: 1.0 mL / min 4. Injection volume: 4 μL 5. Detection wavelength: 228 nm 6. Column temperature: 30 °C 7. Autosampler temperature: room temperature 8. Diluent: Acetonitrile / water 1:1 by volume Unless otherwise specified, the following examples were operated at room temperature.

[0465] Example 1: Preparation of meglumine salt Type A Weighed 1.50 grams of compound GP-046 free form in a 65 mL glass vial, added 40 mL of acetone to form a suspension. Added 990.7 mg of meglumine solid to the above suspension, then placed in a room temperature magnetic stirring for about 3 days. Separated the solid by suction filtration, and placed in a 50 °C vacuum drying overnight, collected the solid to obtain the meglumine salt Type A. The XRPD, TGA, DSC of this example are shown in Figures 1-3 , 1 The H NMR chart is shown in Figure 108 , and its X-ray powder diffraction data are shown in Table 1.

[0466] Table 1

[0467] Examples 2-12: Preparation of meglumine salt Type A (room temperature evaporation) Weighed about 20 mg of meglumine salt solid prepared in Example 1 in a 3 mL vial, added different solvents to dissolve. The filtrate was filtered to a 4 mL single crystal vial using a 0.45 μm polytetrafluoroethylene filter membrane. The single crystal vial was placed in the open air at room temperature to evaporate until solid was precipitated to obtain the meglumine salt Type A. The detailed conditions of the tests involved in this example are shown in Table 2. The X-ray powder diffraction data of Example 2 are shown in Table 3.

[0468] Table 2

[0469] Table 3

[0470] Examples 13-19: Preparation of meglumine salt Type A (rapid cooling) Approximately 30 mg of the meglumine salt solid prepared in Example 2 was weighed into a 3 mL vial, and different solvents were added. The sample solution was then equilibrated at 80 °C for about 2 hours. While hot, the solution was filtered using a 0.45 micron polytetrafluoroethylene filter into another 3 mL vial. After sealing, it was placed at -20 °C until solids precipitated to give meglumine salt Type A. The detailed conditions for the experiments involved in this example are shown in Table 4. The X-ray powder diffraction data for Example 14 are shown in Table 5.

[0471] Table 4

[0472] Table 5

[0473] Examples 20-27: Preparation of meglumine salt Type A (anti-solvent addition) Approximately 30 mg of the meglumine salt solid prepared in Example 2 was weighed into a 20 mL vial, and different solvents were added. The clear solution was filtered using a 0.45 micron polytetrafluoroethylene filter into another 20 mL vial. With magnetic stirring, the anti-solvent was added dropwise to the filtrate until solids precipitated. All samples were placed at room temperature with stirring until meglumine salt Type A was obtained. The detailed conditions for the experiments involved in this example are shown in Table 6. The X-ray powder diffraction data for Example 22 are shown in Table 7.

[0474] Table 6

[0475] Table 7

[0476] Examples 28-37: Preparation of meglumine salt Type A (reverse anti-solvent addition) Approximately 30 mg of the meglumine salt solid prepared in Example 2 was weighed into a 3 mL vial, and different solvents were added. A 20 mL vial was charged with 4 mL of anti-solvent and placed in a refrigerator at 5 °C for about 30 minutes. Then, the meglumine salt solution was filtered into the anti-solvent using a 0.45 micron polytetrafluoroethylene filter, and placed at room temperature with stirring until solids precipitated to give meglumine salt Type A. The detailed conditions for the experiments involved in this example are shown in Table 8. The X-ray powder diffraction data for Example 29 are shown in Table 9.

[0477] Table 8

[0478] Table 9

[0479] Example 38: Preparation of meglumine salt Type B Take 60.4 mg of Compound GP-046 free form in a 3 mL glass vial, add 2 mL of mixed solvent tetrahydrofuran / pure water (19: 1, v / v) solution. Add 40.1 mg of meglumine solid to the above solution, then place in magnetic stirring at room temperature overnight. Centrifugal separation of the solid, and placed at room temperature natural drying for about 4 hours, the collection of solid, to get meglumine salt Type B. The XRPD, TGA, DSC of this example are shown in Figures 4-6 , 1 H NMR chart is shown in Figure 109 , and its X-ray powder diffraction data are shown in Table 10.

[0480] Table 10

[0481]

[0482] Example 39: Preparation of meglumine salt Type D Take 20.1 mg of Compound GP-046 free form in a 5 mL glass vial, add 2 mL of chloroform solution. Add 13.2 mg of meglumine solid to the above solution, then place in magnetic stirring at room temperature for about 3 days. Centrifugal separation of the solid, and placed at room temperature natural drying overnight, the collection of solid, to get meglumine salt Type D. The XRPD, TGA, DSC of this example are shown in Figures 7-9 , 1 H NMR chart is shown in Figure 110 , and its X-ray powder diffraction data are shown in Table 11.

[0483] Table 11

[0484] Example 40: Preparation of meglumine salt Type E Take an appropriate amount of meglumine salt Type D solid in the DSC crucible, heated to 120 °C at a rate of 10 °C / min, and keep for 5 min, then cooled to 40 °C at a rate of 30 °C / min, to get meglumine salt Type E. The XRPD, TGA, DSC of this example are shown in Figures 10-12 , 1 H NMR chart is shown in Figure 111 , and its X-ray powder diffraction data are shown in Table 12.

[0485] Table 12

[0486] Example 41: Preparation of tromethamine salt Type B Weigh 1.50 grams of compound GP-046 free form into a 65 mL glass vial, add 40 mL of acetonitrile to form a suspension. Add 620.8 mg of trisamine solid to the suspension, then place on a magnetic stirrer at room temperature for about 3 days. Isolate the solid by suction filtration, and place in a vacuum oven at 50 °C overnight. Collect the solid to obtain trisamine salt Type B. The XRPD, TGA, DSC of this example are shown in Figures Figures 16-18 1 The H NMR pattern is shown in Figure Figure 112

[0487] Table 13

[0488] Examples 42-48: Preparation of tromethamine salt Type B (rapid cooling) Weigh about 30 mg of trisamine salt solid prepared in Example 41 into a 3 mL vial, add different solvents, then place the sample solution at 80 °C for about 2 hours to equilibrate. While hot, filter the solution using a 0.45 micron polytetrafluoroethylene filter into another 3 mL vial. After sealing, place at -20 °C until solid precipitates to obtain trisamine salt Type B. The detailed conditions of the experiments involved in this example are shown in Table 14. The X-ray powder diffraction data of Example 42 are shown in Table 15.

[0489] Table 14

[0490] Table 15

[0491] Examples 49-51: Preparation of tromethamine salt Type B (gas-liquid diffusion) Weigh about 30 mg of trisamine salt solid prepared in Example 41 into a 3 mL vial, add different solvents to dissolve. Filter the clear solution using a 0.45 micron polytetrafluoroethylene filter into a 4 mL vial. Place the vial open in a 20 mL vial containing 4 mL of anti-solvent. After sealing, place at room temperature until solid precipitates to obtain trisamine salt Type B. The detailed conditions of the experiments involved in this example are shown in Table 16. The X-ray powder diffraction data of Example 49 are shown in Table 17.

[0492] Table 16

[0493] Table 17 ​​

[0494] Example 52: Preparation of tromethamine salt Type B (room temperature evaporation) About 20.1 mg of the tromethamine salt solid prepared in Example 41 was weighed into a 3 mL vial and dissolved in 1 mL of trifluoroethanol / 2-methyltetrahydrofuran (19:5, v / v) mixed solvent. The solution was filtered through a 0.45 μm polytetrafluoroethylene filter into a 4 mL vial. The vial was left open to evaporate at room temperature until solids precipitated to give the tromethamine salt Type B. The X-ray powder diffraction data of this example are shown in Table 18.

[0495] Table 18

[0496] Examples 53-61 : Preparation of Titrates Type B (anti-solvent addition) About 20 mg of the tromethamine salt solid prepared in Example 41 was weighed into a 20 mL vial and dissolved in different solvents. The solution was filtered through a 0.45 μm polytetrafluoroethylene filter into another 20 mL vial. With magnetic stirring, the anti-solvent was added dropwise into the filtrate until solids precipitated. All samples were left to stir at room temperature until the tromethamine salt Type B was obtained. The detailed conditions of the experiments involved in this example are shown in Table 19. The X-ray powder diffraction data of Example 60 are shown in Table 20.

[0497] Table 19

[0498] Table 20

[0499] Examples 62-69: Preparation of Titrates Type B (reverse anti-solvent addition) About 20 mg of the tromethamine salt solid prepared in Example 41 was weighed into a 3 mL vial and dissolved in different solvents. A 4 mL anti-solvent was added into a 20 mL vial and pre-cooled at 5 °C for about 30 minutes. Subsequently, the meglumine salt solution was filtered through a 0.45 μm polytetrafluoroethylene filter into the anti-solvent and left to stir at room temperature until solids precipitated to give the tromethamine salt Type B. The detailed conditions of the experiments involved in this example are shown in Table 21. The X-ray powder diffraction data of Example 63 are shown in Table 22.

[0500] Table 21

[0501] Table 22

[0502] Examples 70-76: Preparation of Titrates Type A Approximately 20 mg of the tromethamine Type B solid prepared in Example 41 was weighed into a 3 mL glass vial and dissolved in different solvents. The supernatant was filtered through a 0.45 μm PTFE membrane into a 4 mL single crystal vial, and then left open at room temperature to evaporate until a solid precipitated, yielding tromethamine Type A. Detailed experimental conditions in this example are shown in Table 23. XRPD, TGA, and DSC of Example 70 are as follows... Figures 13-15 As shown, its X-ray powder diffraction data are shown in Table 24.

[0503] Table 23

[0504] Table 24

[0505]

[0506] Examples 77-79: Preparation of Titrates Type C Approximately 30 mg of the tromethamine Type B solid prepared in Example 41 was weighed into a 3 mL glass vial and dissolved in different solvents. The solution was filtered through a 0.45 μm PTFE membrane into a 4 mL single crystal vial, which was then placed openly into a 20 mL vial pre-filled with 4 mL of antisolvent. After sealing, the sample was placed at room temperature for gas-liquid diffusion until a solid precipitated, yielding tromethamine Type C. Detailed experimental conditions in this example are shown in Table 25. XRPD, TGA, and DSC of Example 77 are as follows... Figures 19-21 As shown, its X-ray powder diffraction data are shown in Table 26.

[0507] Table 25

[0508] Table 26

[0509] Example 80: Preparation of Titrates Type D Weigh 32.7 mg of the tromethamine Type B solid prepared in Example 41 into a 3 mL glass vial, add 2 mL of tetrahydrofuran, and then let stand at 80 ºC for about 3 hours until dissolved. While still hot, filter the above solution into a 3 mL vial using a 0.45 μm PTFE filter membrane. Then let stand at -20 ºC until a solid precipitates, yielding tromethamine Type D. The XRPD, TGA, and DSC of this example are as follows... Figures 22-24 As shown, its X-ray powder diffraction data are shown in Table 27.

[0510] Table 27

[0511] Example 81 : Preparation of Titrates Type E Take 27.3 mg of the Titrated B solid prepared in Example 41 in a 3 mL glass vial, add 0.4 mL trifluoroethanol solution, then filter the solution using a 0.45 micron PTFE filter into a 20 mL vial. Slowly add 10 mL of chloroform to obtain a clear solution. The clear solution was left to sit at -20 °C overnight, then transferred to room temperature and left to evaporate open to the air until solid precipitated to obtain the Titrated E solid. The XRPD, TGA, DSC of this example are shown in Figures 25-27 Table 28, and the X-ray powder diffraction data are shown in Table 28.

[0512] Table 28

[0513] Example 82: Preparation of Titrates Type E Take 27.0 mg of the Titrated B solid prepared in Example 41 in a 3 mL glass vial, add 0.4 mL trifluoroethanol solution, then filter the solution using a 0.45 micron PTFE filter into a 20 mL vial. Slowly add 2 mL of isopropyl ether to precipitate the solid to obtain the Titrated E solid. The X-ray powder diffraction data of this example are shown in Table 29.

[0514] Table 29

[0515] Example 83: Preparation of Urea Cocrystal Type A Take 1.50 g of Compound GP-046 free form in a 65 mL glass vial, add 40 mL of acetone to form a suspension. Add 310.5 mg of urea solid to the suspension, then place in a magnetic stirrer at room temperature for about 3 days. Isolate the solid by suction filtration, and place in a vacuum oven at 50 °C overnight. Collect the solid to obtain the Urea Co-Crystal Type A. The XRPD, TGA, DSC of this example are shown in Figures 28-30 Table 30, and the X-ray powder diffraction data are shown in Table 30. 1 The H NMR chart is shown in Figure 113 Table 30, and the X-ray powder diffraction data are shown in Table 30.

[0516] Table 30

[0517]

[0518] Example 84: Preparation of Potassium Salts Type A Take 1.50 grams of Compound GP-046 free form in a 65 mL glass vial, add 40 mL of acetone to form a suspension. Add 290.8 mg of potassium hydroxide solid to the suspension, then place on a magnetic stir plate at room temperature for about 3 days. Isolate the solid by suction filtration, and place in a vacuum oven at 50 °C overnight. Collect the solid to give the potassium salt Type A. The XRPD, TGA, DSC of this example are shown in Figures 31-33 , 1 The H NMR pattern is shown in Figure 114 , and the X-ray powder diffraction data are shown in Table 31.

[0519] Table 31

[0520] Example 85: Preparation of Potassium Salts Type B Take an appropriate amount of the potassium salt Type A solid prepared in Example 84 onto a hot plate, and heat to 160 °C under a nitrogen purge for 20 minutes to give the potassium salt Type B. The XRPD of this example is shown in Figure 34 , and the X-ray powder diffraction data are shown in Table 32.

[0521] Table 32

[0522] Example 86: Preparation of Calcium Salts Type A Take about 15 mg of Compound GP-046 free form in a 1.5 mL glass vial, add 0.8 mL of ethanol to form a clear solution. Add 1.8 mg of calcium hydroxide solid to the clear solution, then place on a magnetic stir plate at room temperature for about 3 days. Isolate the solid by centrifugation, and place in a vacuum oven at 50 °C overnight. Collect the solid to give the calcium salt Type A. The XRPD, TGA, DSC of this example are shown in Figures 35-37 , 1 The H NMR pattern is shown in Figure 115 , and the X-ray powder diffraction data are shown in Table 33.

[0523] Table 33

[0524] Example 87: Preparation of Calcium Salts Type B Take about 15 mg of Compound GP-046 free form in a 1.5 mL glass vial, add 1.0 mL of acetonitrile to form a clear solution. Add 2.1 mg of calcium hydroxide solid to the clear solution, then place on a magnetic stir plate at room temperature for about 3 days. Isolate the solid by centrifugation, and place in a vacuum oven at 50 °C overnight. Collect the solid to give the calcium salt Type B. The XRPD, TGA, DSC of this example are shown in Figures 38-40 ,1 H NMR chart as shown in Figure 116 Table 34.

[0525] Table 34

[0526] Example 88: Preparation of Calcium Salts Type C Take about 15 milligrams of compound GP-046 free form in a 1.5 milliliter glass vial, add 0.5 milliliter of tetrahydrofuran / pure water (19:1, by volume) mixed solvent to form a clear solution. Add 2.1 milligrams of calcium hydroxide solid to the above clear solution, then placed in room temperature magnetic stirring for about 3 days, and the solid is precipitated to obtain the calcium salt Type C. The XRPD of this example is shown in Figure 41 Table 35.

[0527] Table 35

[0528] Example 89: Preparation of Calcium Salts Type D Take an appropriate amount of calcium salt Type A solid in a DSC crucible, heated to 240 °C at a rate of 10 °C / min, and kept for 2 min, then cooled to 40 °C at a rate of 30 °C / min to obtain the calcium salt Type D. The XRPD, TGA, DSC of this example are shown in Figures 42-44 1 H NMR chart as shown in Figure 117 Table 36.

[0529] Table 36

[0530] Example 90: Preparation of Calcium Salts Type E Take 60.3 milligrams of compound GP-046 free form in a 5 milliliter glass vial, add 3.2 milliliters of ethanol to form a clear solution. Add 8.2 milligrams of calcium hydroxide solid to the above clear solution, then placed in room temperature magnetic stirring overnight, and then placed in 50 °C stirring for about 4 days, and the solid is precipitated. Centrifugal separation of the solid, and placed in 50 °C vacuum drying overnight, and the solid is collected to obtain the calcium salt Type E. The XRPD, TGA, DSC of this example are shown in Figures 45-47 1 H NMR chart as shown in Figure 118 Table 37.

[0531] Table 37 ​​

[0532] Example 91 : Preparation of Magnesium Salts Type A About 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 0.8 mL of ethanol was added to form a clear solution. 1.8 mg of magnesium hydroxide solid was added to the above solution, which was then placed on magnetic stirring at room temperature for about 3 days, and solid was precipitated. The solid was centrifuged and placed in vacuum drying at 50 °C overnight. The solid was collected to give the magnesium salt Type A. The XRPD, TGA, DSC of this example are shown in Figures 48-50 1 The H NMR chart is shown in Figure 119

[0533] Table 38

[0534] Example 92: Preparation of Magnesium Salts Type B About 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 0.5 mL of tetrahydrofuran / pure water (19:1, by volume) mixed solvent system was added to form a clear solution. 3.8 microliters of ammonia water was added to the above solution, which was then placed on magnetic stirring at room temperature for about 3 days, and solid was precipitated to give the ammonium salt Type A. The XRPD of this example is shown in Figure 51

[0535] Table 39

[0536] Example 93: Preparation of Magnesium Salts Type C An appropriate amount of the magnesium salt Type A solid prepared in Example 91 was weighed into a DSC crucible, heated to 220 °C at a rate of 10 °C / min, and kept for 2 min, then cooled to 40 °C at a rate of 30 °C / min to give the magnesium salt Type C. The XRPD of this example is shown in Figure 52

[0537] Table 40

[0538] Example 94: Preparation of Ammonium Salts Type A About 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 0.5 mL of tetrahydrofuran / pure water (19:1, by volume) mixed solvent system was added to form a clear solution. 3.8 microliters of ammonia water was added to the above solution, which was then placed on magnetic stirring at room temperature for about 3 days, and solid was precipitated to give the ammonium salt Type A. The XRPD of this example is shown in​​​​Figure 53 X-ray powder diffraction data are shown in Table 41.

[0539] Table 41

[0540] Example 95: Preparation of Ammonium Salts Type B Approximately 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 0.7 mL of acetone was added to form a clear solution. 3.8 μL of ammonia was added to the clear solution, which was then placed on magnetic stirring at room temperature for about 3 days, and a solid was precipitated. The solid was centrifuged and placed in a vacuum at 50 °C overnight, and the solid was collected to give Ammonium Salt Type B. The XRPD, TGA, DSC of this example are shown in Figures Figures 54-56 1 The1H NMR chart is shown in Figure Figure 120 X-ray powder diffraction data are shown in Table 42.

[0541] Table 42

[0542] Example 96: Preparation of Ammonium Salts Type C Approximately 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 1.0 mL of acetonitrile was added to form a clear solution. 3.8 μL of ammonia was added to the clear solution, which was then placed on magnetic stirring at room temperature for about 3 days, and a solid was precipitated. The solid was centrifuged and placed in a vacuum at 50 °C overnight, and the solid was collected to give Ammonium Salt Type C. The XRPD, TGA, DSC of this example are shown in Figures Figures 57-59 1 The1H NMR chart is shown in Figure Figure 121 X-ray powder diffraction data are shown in Table 43.

[0543] Table 43

[0544] Example 97: Preparation of Ammonium Salts Type D Approximately 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 1.0 mL of acetonitrile was added to form a clear solution. 3.8 μL of ammonia was added to the clear solution, which was then placed on magnetic stirring at room temperature for about 3 days, and a solid was precipitated. The solid was centrifuged and placed in a vacuum at 50 °C overnight, and the solid was collected to give Ammonium Salt Type C. The XRPD, TGA, DSC of this example are shown in Figures Figures 60-62 1 The1H NMR chart is shown in Figure Figure 122 X-ray powder diffraction data are shown in Table 44.

[0545] Table 44

[0546] Example 98: Preparation of Choline Salts Type A ​​​ About 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 0.7 mL of acetone was added to form a clear solution. 12.3 μL of choline was added to the above solution, which was then placed on magnetic stirring at room temperature overnight, and then transferred to a 50-5 °C temperature ramping test (procedure: ramp from room temperature to 50 °C in 20 minutes, hold at 50 °C for 2 hours; then ramp to 5 °C in 450 minutes, and hold at 5 °C for 2 hours; repeat for two cycles), and a solid was precipitated. The solid was centrifuged and placed in a vacuum oven at 50 °C overnight, and the solid was collected to give the choline salt Type A. The XRPD, TGA, DSC of this example are shown in Figures 63-65 , 1 The H NMR chart is shown in Figure 123 , and its X-ray powder diffraction data are shown in Table 45.

[0547] Table 45

[0548] Example 99: Preparation of Lysine Salts Type A About 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 0.7 mL of acetone was added to form a clear solution. 12.3 μL of choline was added to the above solution, which was then placed on magnetic stirring at room temperature overnight, and then transferred to a 50-5 °C temperature ramping test (procedure: ramp from room temperature to 50 °C in 20 minutes, hold at 50 °C for 2 hours; then ramp to 5 °C in 450 minutes, and hold at 5 °C for 2 hours; repeat for two cycles), and a solid was precipitated. The solid was centrifuged and placed in a vacuum oven at 50 °C overnight, and the solid was collected to give the choline salt Type A. The XRPD, TGA, DSC of this example are shown in Figures 66-68 , 1 The H NMR chart is shown in Figure 124 , and its X-ray powder diffraction data are shown in Table 46.

[0549] Table 46

[0550] Example 100: Preparation of Lysine Salts Type B About 15 mg of Compound GP-046 free form was weighed into a 1.5 mL glass vial, 0.7 mL of acetone was added to form a clear solution. 12.3 μL of choline was added to the above solution, which was then placed on magnetic stirring at room temperature overnight, and then transferred to a 50-5 °C temperature ramping test (procedure: ramp from room temperature to 50 °C in 20 minutes, hold at 50 °C for 2 hours; then ramp to 5 °C in 450 minutes, and hold at 5 °C for 2 hours; repeat for two cycles), and a solid was precipitated. The solid was centrifuged and placed in a vacuum oven at 50 °C overnight, and the solid was collected to give the choline salt Type A. The XRPD, TGA, DSC of this example are shown in Figures 69-71 , 1 The H NMR chart is shown in Figure 124 , and its X-ray powder diffraction data are shown in Table 47.

[0551] Table 47

[0552] Example 101 : Preparation of Lysine Salts Type C An appropriate amount of lysine salt Type B solid was weighed into a DSC crucible, heated to 150 °C at a rate of 10 °C / minute and held for 2 minutes, then cooled to 40 °C at a rate of 30 °C / minute to give lysine salt Type C. The XRPD of this example is shown in Figure 72 Table 48, and its X-ray powder diffraction data are shown in Table 48.

[0553] Table 48

[0554] Example 102: Preparation of Lysine Salts Type D An appropriate amount of lysine salt Type B solid was weighed into a DSC crucible, heated to 150 °C at a rate of 10 °C / minute and held for 2 minutes, then cooled to 40 °C at a rate of 30 °C / minute to give lysine salt Type C. The XRPD of this example is shown in

[0555] An appropriate amount of lysine salt Type B solid was weighed into a DSC crucible, heated to 150 °C at a rate of 10 °C / minute and held for 2 minutes, then cooled to 40 °C at a rate of 30 °C / minute to give lysine salt Type C. The XRPD of this example is shown in Figures 73-75 Table 48, and its X-ray powder diffraction data are shown in Table 48. 1 H NMR chart is shown in Figure 126 Table 48, and its X-ray powder diffraction data are shown in Table 48.

[0556] Table 48

[0557] Example 103: Preparation of Betaine Salts Type A An appropriate amount of lysine salt Type B solid was weighed into a DSC crucible, heated to 150 °C at a rate of 10 °C / minute and held for 2 minutes, then cooled to 40 °C at a rate of 30 °C / minute to give lysine salt Type C. The XRPD of this example is shown in Figure 76 Table 48, and its X-ray powder diffraction data are shown in Table 48.

[0558] Table 48

[0559] Example 104: Preparation of Betaine Salts Type B Take about 15 mg of Compound GP-046 free form in a 1.5 mL glass vial, add 1.0 mL of acetonitrile to form a clear solution. Add 6.3 mg of betaine to the above solution, then place it in a magnetic stir at room temperature for about 3 days, solid precipitates. Centrifuge the solid and place it in vacuum drying at 50 °C overnight, collect the solid to get the betaine salt Type B. The XRPD of this example is shown in FIG. 60, and the X-ray powder diffraction data is shown in Table 51. Figure 77

[0560] Table 51

[0561]

[0562] Example 105: Preparation of Betaine Salts Type C Take an appropriate amount of the betaine salt Type B solid prepared in Example 104, place it in vacuum drying at 50 °C overnight, collect the solid to get the betaine salt Type C. The XRPD, TGA, DSC of this example are shown in FIG. 61, Figures 78-80 1 The H NMR chart is shown in FIG. 62, and the X-ray powder diffraction data is shown in Table 52. Figure 127

[0563] Table 52

[0564] Example 106: Preparation of Diethylamine Salts Type A Take about 15 mg of Compound GP-046 free form in a 1.5 mL glass vial, add 1.0 mL of acetonitrile to form a clear solution. Add 5.2 μL of diethylamine to the above solution, then place it in a magnetic stir at room temperature for about 3 days, solid precipitates. Centrifuge the solid and place it in vacuum drying at 50 °C overnight, collect the solid to get the diethylamine salt Type A. The XRPD, TGA, DSC of this example are shown in FIG. 63, Figures 81-83 1 The H NMR chart is shown in FIG. 64, and the X-ray powder diffraction data is shown in Table 53. Figure 128

[0565] Table 53

[0566] Example 107: Preparation of Proline Cocrystal Type A Take 1.50 g of Compound GP-046 free form in a 65 mL glass vial, add 40 mL of acetonitrile to form a suspension. Add 580.8 mg of proline solid to the above suspension, then place it in a magnetic stir at room temperature for about 3 days. Filter the solid and place it in vacuum drying at 50 °C overnight, collect the solid to get the proline co-crystal Type A. The XRPD, TGA, DSC of this example are shown in FIG. 65,​​​​​Figures 84-86 as shown, 1 H NMR chart as shown, Figure 129 as shown, and its X-ray powder diffraction data are shown in Table 54.

[0567] Table 54

[0568]

[0569] Example 108: Preparation of Proline Cocrystal Type B About 10-20 mg of proline co-crystal Type A prepared in Example 107 was weighed into a DVS pan, and after equilibrating at 0% RH, DVS testing was performed (procedure: 0% RH - 95% RH - 0% RH). After the test was completed, the solid was collected to obtain proline co-crystal Type B. The XRPD of this example is shown in Figure 87 as shown, and its X-ray powder diffraction data are shown in Table 55.

[0570] Table 55

[0571] Example 109: Preparation of Hexadecylamine Salts Type A Into a 20 mL glass vial, 300.3 mg of compound GP-046 free form was weighed, and 12 mL of acetone was added to form a clear solution. Into the above solution, 245.9 mg of cetylamine solid was added, and the mixture was placed in a magnetic stirrer at room temperature overnight, and then continued to be placed in a magnetic stirrer at 50 ºC for about 3 hours. The solid was separated by suction filtration, and placed in a vacuum dryer at room temperature overnight. The solid was collected to obtain cetylamine salt Type A. The XRPD, TGA, DSC of this example are shown in Figures 88-90 as shown, 1 H NMR chart as shown, Figure 129 as shown, and its X-ray powder diffraction data are shown in Table 56.

[0572] Table 56

[0573]

[0574] Example 110: Solubility of the crystalline forms S-indobufen free form Form C, the potassium salt Type A, the meglumine salt Type A / E, the tromethamine salt Type A / B / E and the hexadecylamine salt Type A were respectively prepared into suspensions with FaSSIF (fasted state simulated intestinal fluid) and pure water, and then filtered after equilibration for 1 hour, 2 hours, 4 hours and 24 hours to obtain saturated solutions. The content of the samples in the saturated solutions was determined by ultra performance liquid chromatography (UPLC). The test results are shown in Table 57, and the solubility curves are respectively shown in Figures 91-92 The test results show that the solubility of the potassium salt Type A, the meglumine salt Type A / E and the tromethamine salt Type A / B / E of the present application is superior to that of the free form Form C in FaSSIF and pure water, and they are more easily dissolved in the digestive juice of the organism, so that they can be more effectively absorbed and utilized by the organism.

[0575] Table 57

[0576] Example 111 : Compressibility of the crystalline forms Tablet compression was performed by using a hand tablet machine, and a round flat punch capable of compressing into a cylindrical tablet was selected. Appropriate amounts of S-indobufen free form Form C, the potassium salt Type A and the proline co-crystal Type A of the present application were respectively added, and then compressed into round tablets by using a 10 kN pressure. The diameter (D) and thickness (L) of the tablets were measured by using a vernier caliper, and the radial crushing force (hardness, H) was tested by using a tablet hardness tester. The tensile strength of the powder under different hardness was calculated by using the formula T = 2H / πDL, and the test results are shown in Table 58. The test results show that the potassium salt Type A and the proline co-crystal Type A of the present application have greater tensile strength than the free form Form C, indicating that the compressibility of the potassium salt Type A and the proline co-crystal Type A is superior to that of the free form Form C, which is more beneficial to tablet formation and improves the producibility of the drug.

[0577] Table 58

[0578] Example 112: Stability comparison study About 15 mg of potassium salt Type A (initial purity 99.63%), meglumine salt Type A (initial purity 100.00%), tromethamine salt Type B / E (initial purity 100.00%) and urea co-crystal Type A (initial purity 100.00%) were weighed out and placed in a stability chamber at 25 °C / 60% RH and 40 °C / 75% RH, respectively, open to the air. After 1 week, samples were taken for XRPD and HPLC. Meanwhile, about 10 mg of tromethamine salt Type E (initial purity 100.00%) was weighed out and placed in a stability chamber at 80 °C, open to the air. After 1 day, samples were taken for XRPD and HPLC. The results are shown in Table 59, the stability of potassium salt Type A is shown in Figure 93 the stability of meglumine salt Type A is shown in Figure 94 the stability of tromethamine salt Type B is shown in Figure 95 the stability of urea co-crystal Type A is shown in Figure 96 the stability of tromethamine salt Type E is shown in Figure 97 The results show that the potassium salt Type A, meglumine salt Type A, tromethamine salt Type B / E and urea co-crystal Type A of the application have good physical / chemical stability and can meet the requirements for stability during drug production and storage.

[0579] Table 59

[0580] Relative purity = purity after storage / initial purity x 100% Example 113: Hygroscopicity comparison study About 10 mg of S-indobufen free form Form C, tromethamine salt Type B, meglumine salt Type E and urea co-crystal Type A of the application were weighed out and subjected to dynamic vapor sorption (DVS) testing, and then samples were taken for XRPD. The results are shown in Table 60, the DVS of free form Form C is shown in Figure 98 the DVS of tromethamine salt Type B is shown in Figure 99 the DVS of meglumine salt Type E is shown in Figure 100 the DVS of urea co-crystal Type A is shown in Figure 101 The results show that the tromethamine salt Type B, meglumine salt Type E and urea co-crystal Type A of the application have lower hygroscopicity than free form Form C, have lower requirements for post-processing such as drying during production of the drug substance, can remain stable under conventional storage conditions for the drug and have good application prospects.

[0581] Table 60

[0582] The definition of hygroscopicity characteristics and hygroscopic weight gain (Guidelines for Drug Hygroscopicity Test in Chinese Pharmacopoeia 2015 Edition) is as follows: Deliquescence: Absorbing sufficient moisture to form a liquid Extremely hygroscopic: Hygroscopic weight gain is not less than 15% Hygroscopic: Hygroscopic weight gain is less than 15% but not less than 2% Slightly hygroscopic: Hygroscopic weight gain is less than 2% but not less than 0.2% Non-hygroscopic or almost non-hygroscopic: Hygroscopic weight gain is less than 0.2% Example 114: Particle size distribution comparison study About 10-30 mg of potassium salt Type A, meglumine salt Type A, proline co-crystal Type A, urea co-crystal Type A, tromethamine salt Type E and S-indobufen free form Form C were weighed, then about 5 mL Isopar G (containing 0.2% lecithin) was added, the sample to be tested was mixed uniformly, then was added into the SDC injection system to reach a suitable range of light shielding, and the particle size distribution was tested after ultrasonic treatment for 30 seconds. The test results are shown in Table 61, the particle size distribution of potassium salt Type A is shown in Figure 102 , the particle size distribution of meglumine salt Type A is shown in Figure 103 , the particle size distribution of proline co-crystal Type A is shown in Figure 104 , the particle size distribution of urea co-crystal Type A is shown in Figure 105 , the particle size distribution of tromethamine salt Type E is shown in Figure 106 , and the particle size distribution of free form Form C is shown in Figure 107 . The test results show that potassium salt Type A, meglumine salt Type A, proline co-crystal Type A, urea co-crystal Type A and tromethamine salt Type E are unimodal distribution, and free form Form C is multimodal distribution, indicating that potassium salt Type A, meglumine salt Type A, proline co-crystal Type A, urea co-crystal Type A and tromethamine salt Type E have more uniform particle size distribution than free form Form C. Generally, particle size distribution will affect various properties of drug preparations, such as dissolution rate, flowability and bulk density, and uniform particle size distribution is more conducive to controlling drug release rate and improving producibility, thereby affecting the safety, effectiveness and quality controllability of the final drug product.

[0583] Table 61

[0584] Example 115: Adhesion Comparative Study Approximately 100 mg each of the free Form C and tromethamine salt Type B of this invention were weighed and added to a 6 mm circular punch. Tableting was performed using a pressure of 10 kN, with a resting time of approximately half a minute after compression. The final tablet mass was recorded, and the amount of adhesion during the compression process was calculated. The experimental results are shown in Table 62. The results show that the tromethamine salt Type B of this invention is less likely to adhere to the circular punch during tableting than the free Form C, which is more beneficial for saving materials and controlling the stability of the drug loading in the tablets.

[0585] Table 62

[0586] The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A salt of S-indoxylbrufen, characterized in that: the salt of S-indobufen is selected from the group consisting of a meglumine salt, a tromethamine salt, a proline co-crystal, a urea co-crystal, a potassium salt, a calcium salt, a magnesium salt, an ammonium salt, a choline salt, a lysine salt, a betaine salt, a diethylamine salt, a hexadecylamine salt.

2. The salt of S-indobufen of claim 1, which is a S-indobufen meglumine salt; the S-indobufen meglumine salt is a meglumine salt Type A; the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at diffraction angles 2q of 7.4°±0.2°, 11.2°±0.2°, 14.0°±0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at diffraction angles 2q of 15.3°±0.2°, 18.2°±0.2°, 22.9°±0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at diffraction angles 2q of 10.6°±0.2°, 16.7°±0.2°, 22.2°±0.2°.

3. The salt of S-indobufen of claim 1, which is a S-indobufen meglumine salt; the S-indobufen meglumine salt is a meglumine salt Type A; the X-ray powder diffraction pattern of the meglumine salt Type A has characteristic peaks at diffraction angles 2q of any 4, or 5, or 6, or 7, or 8, or 9 of 7.4°±0.2°, 10.6°±0.2°, 11.2°±0.2°, 14.0°±0.2°, 15.3°±0.2°, 16.7°±0.2°, 18.2°±0.2°, 22.2°±0.2°, 22.9°±0.2°.

4. The salt of S-indobufen of claim 2 or 3, the X-ray powder diffraction pattern of the meglumine salt Type A is substantially as shown in Figure 1.

5. The salt of S-indobufen of claim 2 or 3, the meglumine salt Type A has a mass loss gradient of 0.31±0.2 % when heated to 120°±2 ºC by thermogravimetric analysis, or, the meglumine salt Type A starts to melt when heated to 148±2 ºC by differential scanning calorimetry analysis.

6. The salt of S-indobufen of claim 1, which is a S-indobufen meglumine salt; the S-indobufen meglumine salt is a meglumine salt Type B; the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at diffraction angles 2q of 10.7°±0.2°, 16.2°±0.2°, 22.5°±0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at diffraction angles 2q of 6.3°±0.2°, 12.0°±0.2°, 13.9°±0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at diffraction angles 2q of 6.3°±0.2°, 12.0°±0.2°, 13.9°±0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at diffraction angles 2q of 3.2°±0.2°, 21.4°±0.2°, 27.3°±0.2°.

7. The salt of S-indoxole according to claim 1, which is S-indoxole meglumine salt; the X-ray powder diffraction pattern of the meglumine salt Type B has characteristic peaks at diffraction angles 2q of any 4, or 5, or 6, or 7, or 8, or 9 of 3.2°±0.2°, 6.3°±0.2°, 10.7°±0.2°, 12.0°±0.2°, 13.9°±0.2°, 16.2°±0.2°, 21.4°±0.2°, 22.5°±0.2°, 27.3°±0.2°.

8. The salt of S-indoxole according to claim 6 or 7, the X-ray powder diffraction pattern of the meglumine salt Type B is substantially as shown in Figure 4.

9. The salt of S-indoxole according to claim 6 or 7, the meglumine salt Type B has a mass loss gradient of 5.17±0.2% when heated to 120 ±2 °C when subjected to thermogravimetric analysis.

10. The salt of S-indoxole according to claim 6 or 7, the meglumine salt Type B has an endothermic signal when heated to 109 ±2 °C and starts to melt when heated to 150 ±2 °C when subjected to differential scanning calorimetry analysis.

11. The salt of S-indoxole according to claim 1, which is S-indoxole meglumine salt; the S-indoxole meglumine salt is meglumine salt Type D; the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2q of 6.2°±0.2°, 9.3°±0.2°, 12.5°±0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2q of 13.9°±0.2°, 16.2°±0.2°, 27.1°±0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2q of 10.8°±0.2°, 22.7°±0.2°, 30.1°±0.2°.

12. The salt of S-indoxole according to claim 1, which is S-indoxole meglumine salt; the S-indoxole meglumine salt is meglumine salt Type D; the X-ray powder diffraction pattern of the meglumine salt Type D has characteristic peaks at diffraction angles 2q of any 4, or 5, or 6, or 7, or 8, or 9 of 6.2°±0.2°, 9.3°±0.2°, 10.8°±0.2°, 12.5°±0.2°, 13.9°±0.2°, 16.2°±0.2°, 22.7°±0.2°, 27.1°±0.2°, 30.1°±0.2°.

13. The salt of S-indoxole according to claim 11 or 12, wherein the meglumine salt Type D has an X-ray powder diffraction pattern substantially as shown in Figure 7. or, when subjected to thermal gravimetric analysis, the meglumine salt Type D has a mass loss gradient of 15.39 ± 0.2 % when heated to 120 ± 2 °C.

14. The salt of S-indoxole according to claim 1, wherein the S-indoxole meglumine salt is meglumine salt Type E; the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at diffraction angles 2 theta of 7.4° ± 0.2°, 11.0° ± 0.2°, 19.8° ± 0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at diffraction angles 2 theta of 12.7° ± 0.2°, 15.1° ± 0.2°, 18.0° ± 0.2°; or, the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at diffraction angles 2 theta of 3.7° ± 0.2°, 21.2° ± 0.2°, 27.9° ± 0.2°.

15. The salt of S-indoxole according to claim 1, wherein the S-indoxole meglumine salt is meglumine salt Type E; and the X-ray powder diffraction pattern of the meglumine salt Type E has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2 theta of 3.7° ± 0.2°, 7.4° ± 0.2°, 11.0° ± 0.2°, 12.7° ± 0.2°, 15.1° ± 0.2°, 18.0° ± 0.2°, 19.8° ± 0.2°, 21.2° ± 0.2°, 27.9° ± 0.2°.

16. The salt of S-indoxole according to claim 14 or 15, wherein the meglumine salt Type E has an X-ray powder diffraction pattern substantially as shown in Figure 10.

17. The salt of S-indoxole according to claim 14 or 15, wherein, when subjected to thermal gravimetric analysis, the meglumine salt Type E has a mass loss gradient of 1.74 ± 0.2 % when heated to 120 ± 2 °C; or, when subjected to differential scanning calorimetric analysis, the meglumine salt Type E begins to melt at 144 ± 2 °C when heated.

18. The salt of S-indoxole according to any one of claims 2, 3, 6, 7, 11, 12, 14, 15, wherein the molar ratio of S-indoxole to meglumine in the meglumine salt is 0.8 to 1.

2.

19. The salt of S-indoxole according to claim 1, wherein the S-indoxole tromethamine salt is tromethamine salt Type A; the X-ray powder diffraction pattern of the tromethamine salt Type A has characteristic peaks at diffraction angles 2 theta of 4.0° ± 0.2°, 5.7° ± 0.2°, 9.1° ± 0.2°; the X-ray powder diffraction pattern of the tromethamine salt Type A has characteristic peaks at diffraction angles 2 theta of 4.0° ± 0.2°, 5.7° ± 0.2°, 9.1° ± 0.2°; or, the X-ray powder diffraction pattern of the Troxatyl salt Type A has characteristic peaks at diffraction angles 2-theta of 7.9°±0.2°, 20.2°±0.2°, 21.5°±0.2°; or, the X-ray powder diffraction pattern of the Troxatyl salt Type A has characteristic peaks at diffraction angles 2-theta of 23.4°±0.2°, 24.3°±0.2°, 25.3°±0.2°.

20. The salt of S-indobufen according to claim 1, which is S-indobufen Troxatyl salt; the S-indobufen Troxatyl salt is Troxatyl salt Type A; the X-ray powder diffraction pattern of the Troxatyl salt Type A has characteristic peaks at diffraction angles 2-theta of any 4, or 5, or 6, or 7, or 8, or 9 of 4.0°±0.2°, 5.7°±0.2°, 7.9°±0.2°, 9.1°±0.2°, 20.2°±0.2°, 21.5°±0.2°, 23.4°±0.2°, 24.3°±0.2°, 25.3°±0.2°.

21. The salt of S-indobufen according to claim 19 or 20, the X-ray powder diffraction pattern of the Troxatyl salt Type A is substantially as shown in Figure 13.

22. The salt of S-indobufen according to claim 19 or 20, the Troxatyl salt Type A has a mass loss gradient of 3.73±0.2% when heated to 120 ±2ºC when subjected to thermogravimetric analysis, or, the Troxatyl salt Type A has exothermic and endothermic signals when heated to 110±2 ºC, endothermic and exothermic signals when heated to 147±2 ºC, and begins to melt when heated to 154±2 ºC when subjected to differential scanning calorimetry analysis.

23. The salt of S-indobufen according to claim 1, which is S-indobufen Troxatyl salt; the S-indobufen Troxatyl salt is Troxatyl salt Type B; the X-ray powder diffraction pattern of the Troxatyl salt Type B has characteristic peaks at diffraction angles 2-theta of 7.6°±0.2°, 15.2°±0.2°, 22.1°±0.2°; or, the X-ray powder diffraction pattern of the Troxatyl salt Type B has characteristic peaks at diffraction angles 2-theta of 12.8°±0.2°, 17.7°±0.2°, 19.7°±0.2°; or, the X-ray powder diffraction pattern of the Troxatyl salt Type B has characteristic peaks at diffraction angles 2-theta of 6.4°±0.2°, 22.9°±0.2°, 27.3°±0.2°.

24. The salt of S-indobufen of claim 1, which is S-indobufen tromethamine salt; the S-indobufen tromethamine salt is tromethamine salt Type B; the X-ray powder diffraction pattern of the tromethamine salt Type B has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2Q of 6.4°±0.2°, 7.6°±0.2°, 12.8°±0.2°, 15.2°±0.2°, 17.7°±0.2°, 19.7°±0.2°, 22.1°±0.2°, 22.9°±0.2°, 27.3°±0.2°.

25. The salt of S-indobufen of claim 23 or 24, the X-ray powder diffraction pattern of the tromethamine salt Type B is substantially as shown in FIG.

16.

26. The salt of S-indobufen of claim 23 or 24, the tromethamine salt Type B has a mass loss gradient of 0.09±0.2% when heated to 120±2 °C when subjected to thermogravimetric analysis, or, the tromethamine salt Type B begins to melt when heated to 156±2 °C when subjected to differential scanning calorimetry analysis.

27. The salt of S-indobufen of claim 1, which is S-indobufen tromethamine salt; the S-indobufen tromethamine salt is tromethamine salt Type C; the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at diffraction angles 2Q of 5.4°±0.2°, 7.4°±0.2°, 16.0°±0.2°; or, the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at diffraction angles 2Q of 4.5°±0.2°, 11.5°±0.2°, 22.4°±0.2°; or, the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at diffraction angles 2Q of 8.9°±0.2°, 19.8°±0.2°, 24.3°±0.2°.

28. The salt of S-indobufen of claim 1, which is S-indobufen tromethamine salt; the S-indobufen tromethamine salt is tromethamine salt Type C; the X-ray powder diffraction pattern of the tromethamine salt Type C has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2Q of 4.5°±0.2°, 5.4°±0.2°, 7.4°±0.2°, 8.9°±0.2°, 11.5°±0.2°, 16.0°±0.2°, 19.8°±0.2°, 22.4°±0.2°, 24.3°±0.2°.

29. The salt of S-indobufen of claim 27 or 28, the X-ray powder diffraction pattern of the tromethamine salt Type C is substantially as shown in FIG.

19.

30. The salt of S-indoxole of claim 27 or 28, which has a mass loss gradient of 6.33 ± 0.2% when heated to 120 ± 2 °C, when subjected to thermogravimetric analysis, or, which has endothermic and exothermic peaks when heated to 90 ± 2 °C and a melting onset at 155 ± 2 °C when subjected to differential scanning calorimetry analysis, when subjected to differential scanning calorimetry analysis.

31. The salt of S-indoxole of claim 1, which is S-indoxole tromethamine salt; the S-indoxole tromethamine salt is tromethamine salt Type D; the X-ray powder diffraction pattern of the tromethamine salt Type D has characteristic peaks at diffraction angles 2 theta of 5.4° ± 0.2°, 7.5° ± 0.2°, 17.1° ± 0.2°; or, the X-ray powder diffraction pattern of the tromethamine salt Type D has characteristic peaks at diffraction angles 2 theta of 4.5° ± 0.2°, 9.0° ± 0.2°, 24.7° ± 0.2°; or, the X-ray powder diffraction pattern of the tromethamine salt Type D has characteristic peaks at diffraction angles 2 theta of 18.5° ± 0.2°, 19.9° ± 0.2°, 22.8° ± 0.2°.

32. The salt of S-indoxole of claim 1, which is S-indoxole tromethamine salt; the S-indoxole tromethamine salt is tromethamine salt Type D; the X-ray powder diffraction pattern of the tromethamine salt Type D has characteristic peaks at diffraction angles 2 theta of any 4, or 5, or 6, or 7, or 8, or 9 of 4.5° ± 0.2°, 5.4° ± 0.2°, 7.5° ± 0.2°, 9.0° ± 0.2°, 17.1° ± 0.2°, 18.5° ± 0.2°, 19.9° ± 0.2°, 22.8° ± 0.2°, 24.7° ± 0.2°.

33. The salt of S-indoxole of claim 31 or 32, the X-ray powder diffraction pattern of the tromethamine salt Type D is substantially as shown in Figure 22.

34. The salt of S-indoxole of claim 31 or 32, which has a mass loss gradient of 6.74 ± 0.2% when heated to 120 ± 2 °C, when subjected to thermogravimetric analysis, or, which has endothermic and exothermic peaks when heated to 103 °C, an exothermic peak when heated to 133 ± 2 °C, and a melting onset at 154 ± 2 °C when subjected to differential scanning calorimetry analysis, when subjected to differential scanning calorimetry analysis, when subjected to thermogravimetric analysis.

35. The salt of S-indoxole of claim 1, which is S-indoxole tromethamine salt; the S-indoxole tromethamine salt is tromethamine salt Type E; the X-ray powder diffraction pattern of the tromethamine salt Type E has characteristic peaks at diffraction angles 2 theta of 4.8° ± 0.2°, 10.2° ± 0.2°, 14.4° ± 0.2°; the X-ray powder diffraction pattern of the tromethamine salt Type E has characteristic peaks at diffraction angles 2 theta of 4.8° ± 0.2°, 10.2° ± 0.2°, 14.4° ± 0.2°; or, the X-ray powder diffraction pattern of the aminotrizolyl salt Type E has characteristic peaks at diffraction angles 2Q of 9.5°±0.2°, 15.9°±0.2°, 19.4°±0.2°; or, the X-ray powder diffraction pattern of the aminotrizolyl salt Type E has characteristic peaks at diffraction angles 2Q of 18.7±0.2°, 19.8°±0.2°, 23.8°±0.2°.

36. The salt of S-indobufen according to claim 1, which is S-indobufen aminotrizolyl salt; the S-indobufen aminotrizolyl salt is aminotrizolyl salt Type E; the X-ray powder diffraction pattern of the aminotrizolyl salt Type E has characteristic peaks at diffraction angles 2Q of any 4, or 5, or 6, or 7, or 8, or 9 of 4.8°±0.2°, 9.5°±0.2°, 10.2°±0.2°, 14.4°±0.2°, 15.9°±0.2°, 18.7°±0.2°, 19.4°±0.2°, 19.8°±0.2°, 23.8°±0.2°.

37. The salt of S-indobufen according to claim 35 or 36, the X-ray powder diffraction pattern of the aminotrizolyl salt Type E is substantially as shown in Figure 25.

38. The salt of S-indobufen according to claim 35 or 36, the aminotrizolyl salt Type E has a mass loss gradient of 1.18±0.2% when heated to 120 ±2ºC when subjected to thermogravimetric analysis, or, the aminotrizolyl salt Type E begins to melt when heated to 153 ±2ºC when subjected to differential scanning calorimetry analysis.

39. The salt of S-indobufen according to any one of claims 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, the molar ratio of S-indobufen to aminotrizolyl in the aminotrizolyl salt is: 0.8~1.

2.

40. The salt of S-indobufen according to claim 1, which is S-indobufen urea co-crystal; the S-indobufen urea co-crystal is urea co-crystal Type A, the X-ray powder diffraction pattern of the urea co-crystal Type A has characteristic peaks at diffraction angles 2Q of 5.9°±0.2°, 12.7°±0.2°, 14.3°±0.2°; or, the X-ray powder diffraction pattern of the urea co-crystal Type A has characteristic peaks at diffraction angles 2Q of 17.5°±0.2°, 18.7°±0.2°, 23.5°±0.2°; or, the X-ray powder diffraction pattern of the urea co-crystal Type A has characteristic peaks at diffraction angles 2Q of 20.3°±0.2°, 22.7°±0.2°, 24.3°±0.2°.

41. The salt of S-indobufen of claim 1, which is a S-indobufen urea co-crystal; the S-indobufen urea co-crystal is a urea co-crystal Type A, the X-ray powder diffraction pattern of the urea co-crystal Type A has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2Q of 5.9°±0.2°, 12.7°±0.2°, 14.3°±0.2°, 17.5°±0.2°, 18.7°±0.2°, 20.3°±0.2°, 22.7°±0.2°, 23.5°±0.2°, 24.3°±0.2°.

42. The salt of S-indobufen of claim 40 or 41, the X-ray powder diffraction pattern of the urea co-crystal Type A is substantially as shown in FIG.

28.

43. The salt of S-indobufen of claim 40 or 41, the urea co-crystal Type A has a mass loss gradient of 0.26±0.2% when heated to 120±2 °C when subjected to thermogravimetric analysis; or, the urea co-crystal Type A starts to melt when heated to 148 ±2 °C when subjected to differential scanning calorimetry analysis.

44. The salt of S-indobufen of claim 40 or 41, the molar ratio of S-indobufen to urea in the urea co-crystal is: 0.8~1.

2.

45. The salt of S-indobufen of claim 1, which is a S-indobufen potassium salt; the S-indobufen potassium salt is a potassium salt Type A; the X-ray powder diffraction pattern of the potassium salt Type A has characteristic peaks at the diffraction angles 2Q of 12.2°±0.2°, 14.5°±0.2°, 25.6°±0.2°; or, the X-ray powder diffraction pattern of the potassium salt Type A has characteristic peaks at the diffraction angles 2Q of 15.2°±0.2°, 24.1°±0.2°, 24.6°±0.2°; or, the X-ray powder diffraction pattern of the potassium salt Type A has characteristic peaks at the diffraction angles 2Q of 4.1°±0.2°, 20.4°±0.2°, 20.9°±0.2°.

46. The salt of S-indobufen of claim 1, which is a S-indobufen potassium salt; the S-indobufen potassium salt is a potassium salt Type A; the X-ray powder diffraction pattern of the potassium salt Type A has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2Q of 4.1°±0.2°, 12.2°±0.2°, 14.5°±0.2°, 15.2°±0.2°, 20.4°±0.2°, 20.9°±0.2°, 24.1°±0.2°, 24.6°±0.2°, 25.6°±0.2°.

47. The salt of S-indobufen of claim 45 or 46, the X-ray powder diffraction pattern of the potassium salt Type A is substantially as shown in FIG.

31.

48. The salt of S-indoxamine of claim 45 or 46, when subjected to thermogravimetric analysis, the potassium salt Type A has a mass loss gradient of 4.76 ± 0.2% when heated to 120 ± 2 °C; or, when subjected to differential scanning calorimetry analysis, the potassium salt Type A has an endothermic peak when heated to 160 ± 2 °C, endothermic and exothermic peaks when heated to 199 ± 2 and 202 ± 2 °C, and begins to melt when heated to 213 ± 2 °C.

49. The salt of S-indoxamine of claim 1, which is a potassium salt of S-indoxamine; the potassium salt of S-indoxamine is potassium salt Type B; the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at diffraction angles 2 theta of 5.2° ± 0.2°, 12.6° ± 0.2°, 24.3° ± 0.2°; or, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at diffraction angles 2 theta of 6.5° ± 0.2°, 14.4° ± 0.2°, 22.6° ± 0.2°, or, the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at diffraction angles 2 theta of 4.2° ± 0.2°, 15.1° ± 0.2°, 25.9° ± 0.2°.

50. The salt of S-indoxamine of claim 1, which is a potassium salt of S-indoxamine; the potassium salt of S-indoxamine is potassium salt Type B; the X-ray powder diffraction pattern of the potassium salt Type B has characteristic peaks at diffraction angles 2 theta of any 4, or 5, or 6, or 7, or 8, or 9 of 4.2° ± 0.2°, 5.2° ± 0.2°, 6.5° ± 0.2°, 12.6° ± 0.2°, 14.4° ± 0.2°, 15.1° ± 0.2°, 22.6° ± 0.2°, 24.3° ± 0.2°, 25.9° ± 0.2°.

51. The salt of S-indoxamine of claim 49 or 50, the X-ray powder diffraction pattern of the potassium salt Type B is substantially as shown in FIG.

34.

52. The salt of S-indoxamine of any one of claims 45, 46, 49, 50, the molar ratio of S- indoxamine to potassium ion in the potassium salt is: 0.8 ~ 1.

2.

53. The salt of S-indoxamine of claim 1, which is a calcium salt of S-indoxamine; the calcium salt of S-indoxamine is calcium salt Type A; the X-ray powder diffraction pattern of the calcium salt Type A has characteristic peaks at diffraction angles 2 theta of 6.3° ± 0.2°, 9.6° ± 0.2°, 24.3° ± 0.2°; or, the X-ray powder diffraction pattern of the calcium salt Type A has characteristic peaks at diffraction angles 2 theta of 6.6° ± 0.2°, 9.2° ± 0.2°, 12.7° ± 0.2°; or, the X-ray powder diffraction pattern of the calcium salt Type A has characteristic peaks at diffraction angles 2 theta of 5.3° ± 0.2°, 12.0° ± 0.2°, 25.6° ± 0.2°.

54. The salt of S-indoxamine of claim 1, which is S-indoxamine calcium salt; the S-indoxamine calcium salt is calcium salt Type A; the X-ray powder diffraction pattern of the calcium salt Type A has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2Q of 5.3°±0.2°, 6.3°±0.2°, 6.6°±0.2°, 9.2°±0.2°, 9.6°±0.2°, 12.0°±0.2°, 12.7°±0.2°, 24.3°±0.2°, 25.6°±0.2°.

55. The salt of S-indoxamine of claim 53 or 54, the X-ray powder diffraction pattern of the calcium salt Type A is substantially as shown in FIG.

35.

56. The salt of S-indoxamine of claim 53 or 54, the calcium salt Type A has a mass loss gradient of 4.73±0.2% when heated to 150 ±2ºC when subjected to thermogravimetric analysis.

57. The salt of S-indoxamine of claim 53 or 54, the calcium salt Type A has an endothermic peak when heated to 150 ±2ºC, and endothermic and exothermic peaks when heated to 187±2 and 220 ±2ºC when subjected to differential scanning calorimetry analysis.

58. The salt of S-indoxamine of claim 1, which is S-indoxamine calcium salt; the S-indoxamine calcium salt is calcium salt Type B; the X-ray powder diffraction pattern of the calcium salt Type B has characteristic peaks at diffraction angles 2Q of 5.8°±0.2°, 18.1°±0.2°, 23.3°±0.2°; or, the X-ray powder diffraction pattern of the calcium salt Type B has characteristic peaks at diffraction angles 2Q of 10.6°±0.2°, 20.0°±0.2°.

59. The salt of S-indoxamine of claim 1, which is S-indoxamine calcium salt; the S-indoxamine calcium salt is calcium salt Type B; the X-ray powder diffraction pattern of the calcium salt Type B has characteristic peaks at any 4, or 5 of diffraction angles 2Q of 5.8°±0.2°, 10.6°±0.2°, 18.1°±0.2°, 20.0°±0.2°, 23.3°±0.2°.

60. The salt of S-indoxamine of claim 58 or 59, the X-ray powder diffraction pattern of the calcium salt Type B is substantially as shown in FIG.

38.

61. The salt of S-indoxamine of claim 58 or 59, the calcium salt Type B has a mass loss gradient of 2.69±0.2% when heated to 160±2ºC, and a mass loss gradient of 4.36±0.2% when heated to 300 ±2ºC when subjected to thermogravimetric analysis; or, the calcium salt Type B has an endothermic peak when heated to 200±2ºC when subjected to differential scanning calorimetry analysis.

62. The salt of S-indoxamine of claim 1, which is a S-indoxamine calcium salt; the S-indoxamine calcium salt is a calcium salt Type C; the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at diffraction angles 2q of 11.6°±0.2°, 19.0°±0.2°, 24.9°±0.2°; or, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at diffraction angles 2q of 14.3°±0.2°, 23.3°±0.2°, 26.5°±0.2°; or, the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at diffraction angles 2q of 21.1°±0.2°, 25.8°±0.2°, 27.4°±0.2°.

63. The salt of S-indoxamine of claim 1, which is a S-indoxamine calcium salt; the S-indoxamine calcium salt is a calcium salt Type C; the X-ray powder diffraction pattern of the calcium salt Type C has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2q of 11.6°±0.2°, 14.3°±0.2°, 19.0°±0.2°, 21.1°±0.2°, 23.3°±0.2°, 24.9°±0.2°, 25.8°±0.2°, 26.5°±0.2°, 27.4°±0.2°.

64. The salt of S-indoxamine of claim 62 or 63, the X-ray powder diffraction pattern of the calcium salt Type C is substantially as depicted in FIG.

41.

65. The salt of S-indoxamine of claim 1, which is a S-indoxamine calcium salt; the S-indoxamine calcium salt is a calcium salt Type D; the X-ray powder diffraction pattern of the calcium salt Type D has characteristic peaks at diffraction angles 2q of 5.7°±0.2°, 7.0°±0.2°, 8.3°±0.2°.

66. The salt of S-indoxamine of claim 65, the X-ray powder diffraction pattern of the calcium salt Type D is substantially as depicted in FIG.

42.

67. The salt of S-indoxamine of claim 65, when subjected to thermal gravimetric analysis, the calcium salt Type D has a mass loss gradient of 1.54±0.2% when heated to 260±2ºC; or, when subjected to differential scanning calorimetry analysis, the calcium salt Type D begins to melt when heated to 302±2ºC.

68. The salt of S-indoxamine of claim 1, which is a S-indoxamine calcium salt; the S-indoxamine calcium salt is a calcium salt Type E; the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 5.9°±0.2°, 8.9°±0.2°, 10.5°±0.2°; or, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 5.3°±0.2°, 6.8°±0.2°, 26.5°±0.2°; or, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2q of 5.3°±0.2°, 6.8°±0.2°, 26.5°±0.2°; or, the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2-theta of 11.8°±0.2°, 17.0°±0.2°, 17.9°±0.2°.

69. The salt of S-indoxamine of claim 1, which is a S-indoxamine calcium salt; the S-indoxamine calcium salt is calcium salt Type E; the X-ray powder diffraction pattern of the calcium salt Type E has characteristic peaks at diffraction angles 2-theta of any 4, or 5, or 6, or 7, or 8, or 9 of 5.3°±0.2°, 5.9°±0.2°, 6.8°±0.2°, 8.9°±0.2°, 10.5°±0.2°, 11.8°±0.2°, 17.0°±0.2°, 17.9°±0.2°, 26.5°±0.2°.

70. The salt of S-indoxamine of claim 68 or 69, the X-ray powder diffraction pattern of the calcium salt Type E is substantially as shown in FIG.

45.

71. The salt of S-indoxamine of claim 68 or 69, when subjected to thermogravimetric analysis, the calcium salt Type E has a mass loss gradient of 3.17±0.2% when heated to 130 ±2ºC, and a mass loss gradient of 3.49±0.2% when heated to 260 ±2ºC; or, when subjected to differential scanning calorimetry analysis, the calcium salt Type E has an endothermic peak when heated to 148 ±2ºC, an endothermic peak when heated to 223±2 ºC, and an endothermic peak and an exothermic peak when heated to 254 ±2ºC.

72. The salt of S-indoxamine of any one of claims 53, 54, 58, 59, 62, 63, 65, 68, 69, the molar ratio of S-indoxamine to calcium ion in the calcium salt is: 1.6~2.

4.

73. The salt of S-indoxamine of claim 1, which is a S-indoxamine magnesium salt; the S-indoxamine magnesium salt is magnesium salt Type A; the X-ray powder diffraction pattern of the magnesium salt Type A has characteristic peaks at diffraction angles 2-theta of 5.1°±0.2°, 6.6°±0.2°, 13.1°±0.2°; or, the X-ray powder diffraction pattern of the magnesium salt Type A has characteristic peaks at diffraction angles 2-theta of 9.8°±0.2°, 24.4°±0.2°, 24.8°±0.2°.

74. The salt of S-indoxamine of claim 1, which is a S-indoxamine magnesium salt; the S-indoxamine magnesium salt is magnesium salt Type A; the X-ray powder diffraction pattern of the magnesium salt Type A has characteristic peaks at diffraction angles 2-theta of any 4, or 5, or 6 of 5.1°±0.2°, 6.6°±0.2°, 9.8°±0.2°, 13.1°±0.2°, 24.4°±0.2°, 24.8°±0.2°.

75. The salt of S-indoxole of claim 73 or 74, wherein the magnesium salt Type A has an X-ray powder diffraction pattern substantially as shown in FIG.

48.

76. The salt of S-indoxole of claim 73 or 74, wherein the magnesium salt Type A has a mass loss gradient of 8.83 ± 0.2% when heated to 200 ± 2ºC when subjected to thermogravimetric analysis; or, has an endothermic peak when heated to 187 ± 2ºC, an endothermic peak and an exothermic peak when heated to 200 ± 2ºC, and begins to melt when heated to 247 ± 2ºC when subjected to differential scanning calorimetry analysis.

77. The salt of S-indoxole of claim 1, wherein the salt of S-indoxole is a magnesium salt of S-indoxole; and the magnesium salt of S-indoxole is magnesium salt Type B; the X-ray powder diffraction pattern of the magnesium salt Type B has characteristic peaks at diffraction angles 2 theta (2q) of 5.8° ± 0.2°, 7.2° ± 0.2°, 10.2° ± 0.2°; or, the X-ray powder diffraction pattern of the magnesium salt Type B has characteristic peaks at diffraction angles 2 theta (2q) of 6.8° ± 0.2°, 12.5° ± 0.2°, 25.1° ± 0.2°; or, the X-ray powder diffraction pattern of the magnesium salt Type B has characteristic peaks at diffraction angles 2 theta (2q) of 4.8° ± 0.2°, 23.4° ± 0.2°, 26.4° ± 0.2°.

78. The salt of S-indoxole of claim 1, wherein the salt of S-indoxole is a magnesium salt of S-indoxole; and the magnesium salt of S-indoxole is magnesium salt Type B; and the X-ray powder diffraction pattern of the magnesium salt Type B has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2 theta (2q) of 4.8° ± 0.2°, 5.8° ± 0.2°, 6.8° ± 0.2°, 7.2° ± 0.2°, 10.2° ± 0.2°, 12.5° ± 0.2°, 23.4° ± 0.2°, 25.1° ± 0.2°, 26.4° ± 0.2°.

79. The salt of S-indoxole of claim 77 or 78, wherein the magnesium salt Type B has an X-ray powder diffraction pattern substantially as shown in FIG.

51.

80. The salt of S-indoxole of claim 1, wherein the salt of S-indoxole is a magnesium salt of S-indoxole; and the magnesium salt of S-indoxole is magnesium salt Type C; the X-ray powder diffraction pattern of the magnesium salt Type C has characteristic peaks at diffraction angles 2 theta (2q) of 4.9° ± 0.2°, 7.0° ± 0.2°, 9.8° ± 0.2°; or, the X-ray powder diffraction pattern of the magnesium salt Type C has characteristic peaks at diffraction angles 2 theta (2q) of 14.1° ± 0.2°, 26.6° ± 0.2°.

81. The salt of S-indobufen of claim 1, which is a magnesium salt of S-indobufen; the magnesium salt of S-indobufen is a magnesium salt Type C; the X-ray powder diffraction pattern of the magnesium salt Type C has characteristic peaks at any 4 of 2-theta = 4.9°±0.2°, 7.0°±0.2°, 9.8°±0.2°, 14.1°±0.2°, 26.6°±0.2°, or 5 of them.

82. The salt of S-indobufen of claim 80 or 81, the X-ray powder diffraction pattern of the magnesium salt Type C is substantially as shown in FIG.

52.

83. The salt of S-indobufen of any one of claims 73, 74, 77, 78, 80, 81, the molar ratio of S-indobufen to magnesium ion in the magnesium salt is: 1.6~2.

4.

84. The salt of S-indobufen of claim 1, which is an ammonium salt of S-indobufen; the ammonium salt of S-indobufen is an ammonium salt Type A; or, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at 2-theta = 4.2°±0.2°, 8.4°±0.2°, 12.6°±0.2°; or, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at 2-theta = 15.3°±0.2°, 19.8°±0.2°, 24.3°±0.2°; or, the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at 2-theta = 14.6°±0.2°, 16.8°±0.2°, 25.4°±0.2°.

85. The salt of S-indobufen of claim 1, which is an ammonium salt of S-indobufen; the ammonium salt of S-indobufen is an ammonium salt Type A; the X-ray powder diffraction pattern of the ammonium salt Type A has characteristic peaks at any 4 of 2-theta = 4.2°±0.2°, 8.4°±0.2°, 12.6°±0.2°, 14.6°±0.2°, 15.3°±0.2°, 16.8°±0.2°, 19.8°±0.2°, 24.3°±0.2°, 25.4°±0.2°, or 5 of them, or 6 of them, or 7 of them, or 8 of them, or 9 of them.

86. The salt of S-indobufen of claim 84 or 85, the X-ray powder diffraction pattern of the ammonium salt Type A is substantially as shown in FIG.

53.

87. The salt of S-indobufen of claim 1, which is an ammonium salt of S-indobufen; the ammonium salt of S-indobufen is an ammonium salt Type B; the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at 2-theta = 11.7°±0.2°, 15.7°±0.2°, 23.6°±0.2°; or, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at 2-theta = 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°; or, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at 2-theta = 7.8°±0.2°, 22.1°±0.2°, 25.1°±0.2°. or, the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2-theta of 8.4°±0.2°, 12.6°±0.2°, 20.8°±0.2°.

88. The salt of S-indobufen according to claim 1, which is an ammonium salt of S-indobufen; the ammonium salt of S-indobufen is ammonium salt Type B; the X-ray powder diffraction pattern of the ammonium salt Type B has characteristic peaks at diffraction angles 2-theta of any 4, or 5, or 6, or 7, or 8, or 9 of 7.8°±0.2°, 8.4°±0.2°, 11.7°±0.2°, 12.6°±0.2°, 15.7°±0.2°, 20.8°±0.2°, 22.1°±0.2°, 23.6°±0.2°, 25.1°±0.2°.

89. The salt of S-indobufen according to claim 87 or 88, wherein the molar ratio of S-indobufen to ammonium ion in the ammonium salt of S-indobufen is 1.6~2.

4.

90. The salt of S-indobufen according to claim 87 or 88, wherein the X-ray powder diffraction pattern of the ammonium salt Type B is substantially as shown in FIG.

54.

91. The salt of S-indobufen according to claim 87 or 88, wherein the ammonium salt Type B has a mass loss gradient of 6.68±0.2% when heated to 150±2 °C when subjected to thermogravimetric analysis; or, the ammonium salt Type B has an endothermic peak when heated to 139±2 °C and begins to melt when heated to 197 ±2 °C when subjected to differential scanning calorimetry analysis.

92. The salt of S-indobufen according to claim 1, which is an ammonium salt of S-indobufen; the ammonium salt of S-indobufen is ammonium salt Type C; the X-ray powder diffraction pattern of the ammonium salt Type C has characteristic peaks at diffraction angles 2-theta of 8.4°±0.2°, 14.8°±0.2°, 19.6°±0.2°; or, the X-ray powder diffraction pattern of the ammonium salt Type C has characteristic peaks at diffraction angles 2-theta of 12.7°±0.2°, 24.1°±0.2°, 26.6°±0.2°; or, the X-ray powder diffraction pattern of the ammonium salt Type C has characteristic peaks at diffraction angles 2-theta of 18.8°±0.2°, 22.7°±0.2°, 26.0°±0.2°.

93. The salt of S-indobufen according to claim 1, which is an ammonium salt of S-indobufen; the ammonium salt of S-indobufen is ammonium salt Type C; the X-ray powder diffraction pattern of the ammonium salt Type C has characteristic peaks at diffraction angles 2-theta of any 4, or 5, or 6, or 7, or 8, or 9 of 8.4°±0.2°, 12.7°±0.2°, 14.8°±0.2°, 18.8°±0.2°, 19.6°±0.2°, 22.7°±0.2°, 24.1°±0.2°, 26.0°±0.2°, 26.6°±0.2°.

94. The salt of S-indobufen according to claim 92 or 93, wherein the molar ratio of S- indobufen to ammonium ion in the S-indobufen ammonium salt is 1.5 to 1.

7.

95. The salt of S-indobufen according to claim 92 or 93, wherein the X-ray powder diffraction pattern of the ammonium salt Type C is substantially as shown in FIG.

57.

96. The salt of S-indobufen according to claim 92 or 93, wherein the ammonium salt Type C has a mass loss gradient of 8.60 ± 0.2% when heated to 150 ± 2 °C when subjected to thermogravimetric analysis; or, the ammonium salt Type C has an endothermic peak when heated to 137 ± 2 °C and begins to melt when heated to 198 ± 2 °C when subjected to differential scanning calorimetry analysis.

97. The salt of S-indobufen according to claim 1, which is a S-indobufen ammonium salt; wherein the S-indobufen ammonium salt is ammonium salt Type D; wherein the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2 theta of 5.1° ± 0.2°, 8.8° ± 0.2°, 19.6° ± 0.2°; or, wherein the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2 theta of 15.1° ± 0.2°, 18.9° ± 0.2°, 24.6° ± 0.2°; or, wherein the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at diffraction angles 2 theta of 4.4° ± 0.2°, 13.3° ± 0.2°, 25.6° ± 0.2°.

98. The salt of S-indobufen according to claim 1, which is a S-indobufen ammonium salt; wherein the S-indobufen ammonium salt is ammonium salt Type D; and wherein the X-ray powder diffraction pattern of the ammonium salt Type D has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2 theta of 4.4° ± 0.2°, 5.1° ± 0.2°, 8.8° ± 0.2°, 13.3° ± 0.2°, 15.1° ± 0.2°, 18.9° ± 0.2°, 19.6° ± 0.2°, 24.6° ± 0.2°, 25.6° ± 0.2°.

99. The salt of S-indobufen according to claim 97 or 98, wherein the molar ratio of S- indobufen to ammonium ion in the S-indobufen ammonium salt is 4 to 6.

100. The salt of S-indobufen according to claim 97 or 98, wherein the X-ray powder diffraction pattern of the ammonium salt Type D is substantially as shown in FIG.

60.

101. The salt of S-indobufen according to claim 97 or 98, wherein the ammonium salt Type D has a mass loss gradient of 3.27 ± 0.2% when heated to 150 ± 2 °C when subjected to thermogravimetric analysis; or, the ammonium salt Type D has an endothermic peak when heated to 132 ± 2 °C and begins to melt when heated to 199 ± 2 °C when subjected to differential scanning calorimetry analysis.

102. The salt of S-indobufen according to claim 1, which is S-indobufen choline salt; the S-indobufen choline salt is choline salt Type A; the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at diffraction angles 2q of 12.7°±0.2°, 16.4°±0.2°, 19.3°±0.2°; or, the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at diffraction angles 2q of 11.4°±0.2°, 15.2°±0.2°, 23.4°±0.2°; or, the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at diffraction angles 2q of 15.7°±0.2°, 20.2°±0.2°, 23.2°±0.2°.

103. The salt of S-indobufen according to claim 1, which is S-indobufen choline salt; the S-indobufen choline salt is choline salt Type A; the X-ray powder diffraction pattern of the choline salt Type A has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2q of 11.4°±0.2°, 12.7°±0.2°, 15.2°±0.2°, 15.7°±0.2°, 16.4°±0.2°, 19.3°±0.2°, 20.2°±0.2°, 23.2°±0.2°, 23.4°±0.2°.

104. The salt of S-indobufen according to claim 102 or 103, wherein the molar ratio of S-indobufen to choline in the choline salt is 0.8-1.

2.

105. The salt of S-indobufen according to claim 102 or 103, wherein the X-ray powder diffraction pattern of the choline salt Type A is substantially as shown in FIG.

63.

106. The salt of S-indobufen according to claim 102 or 103, wherein the choline salt Type A has a mass loss gradient of 4.17±0.2% when heated to 120±2ºC when subjected to thermogravimetric analysis; or, the choline salt Type A has an endothermic peak when heated to 135±2ºC and begins to melt when heated to 214±2ºC when subjected to differential scanning calorimetry analysis.

107. The salt of S-indobufen according to claim 1, which is S-indobufen lysine salt; the S-indobufen lysine salt is lysine salt Type A; the X-ray powder diffraction pattern of the lysine salt Type A has characteristic peaks at diffraction angles 2q of 5.5°±0.2°, 9.1°±0.2°, 10.1°±0.2°; or, the X-ray powder diffraction pattern of the lysine salt Type A has characteristic peaks at diffraction angles 2q of 5.1°±0.2°, 21.3°±0.2°, 25.9°±0.2°; or, the X-ray powder diffraction pattern of the lysine salt Type A has characteristic peaks at diffraction angles 2q of 5.1°±0.2°, 21.3°±0.2°, 25.9°±0.2°. or, the X-ray powder diffraction pattern of the lysine salt Type A has characteristic peaks at diffraction angles 2Q of 19.8°±0.2°, 22.2°±0.2°, 23.8°±0.2°.

108. The salt of S-indoxamine of claim 1, which is S-indoxamine lysine salt; the S-indoxamine lysine salt is lysine salt Type A; the X-ray powder diffraction pattern of the lysine salt Type A has characteristic peaks at diffraction angles 2Q of any 4, or 5, or 6, or 7, or 8, or 9 of 5.1°±0.2°, 5.5°±0.2°, 9.1°±0.2°, 10.1°±0.2°, 19.8°±0.2°, 21.3°±0.2°, 22.2°±0.2°, 23.8°±0.2°, 25.9°±0.2°.

109. The salt of S-indoxamine of claim 107 or 108, wherein the molar ratio of S- indoxamine to lysine in the S-indoxamine lysine salt is 0.8-1.

2.

110. The salt of S-indoxamine of claim 107 or 108, wherein the X-ray powder diffraction pattern of the lysine salt Type A is substantially as shown in FIG.

66.

111. The salt of S-indoxamine of claim 107 or 108, wherein the lysine salt Type A has a mass loss gradient of 2.86±0.2% when heated to 150 ±2ºC when subjected to thermogravimetric analysis; or, the lysine salt Type A has an endothermic peak and an exothermic peak when heated to 150 ±2ºC and begins to melt when heated to 205 ±2ºC when subjected to differential scanning calorimetry analysis.

112. The salt of S-indoxamine of claim 1, which is S-indoxamine lysine salt; the S- indoxamine lysine salt is lysine salt Type B; the X-ray powder diffraction pattern of the lysine salt Type B has characteristic peaks at diffraction angles 2Q of 5.1°±0.2°, 6.1°±0.2°, 19.4°±0.2°; or, the X-ray powder diffraction pattern of the lysine salt Type B has characteristic peaks at diffraction angles 2Q of 7.0°±0.2°, 12.1°±0.2°, 21.2°±0.2°, 24.4°±0.2°.

113. The salt of S-indoxamine of claim 1, which is S-indoxamine lysine salt; the S- indoxamine lysine salt is lysine salt Type B; the X-ray powder diffraction pattern of the lysine salt Type B has characteristic peaks at diffraction angles 2Q of any 4, or 5, or 6, or 7 of 5.1°±0.2°, 6.1°±0.2°, 7.0°±0.2°, 12.1°±0.2°, 19.4°±0.2°, 21.2°±0.2°, 24.4°±0.2°.

114. The salt of S-indobufen according to claim 112 or 113, wherein the molar ratio of S- indobufen to lysine in the lysine salt is 0.8 to 1.

4.

115. The salt of S-indobufen according to claim 112 or 113, wherein the X-ray powder diffraction pattern of the lysine salt Type B is substantially as shown in FIG.

69.

116. The salt of S-indobufen according to claim 112 or 113, wherein the lysine salt Type B has a mass loss gradient of 7.69 ± 0.2% when heated to 150 ± 2ºC when subjected to thermogravimetric analysis; or, wherein the lysine salt Type B has an endothermic peak when heated to 94 ± 2ºC, an exothermic peak when heated to 184 ± 2ºC, and begins to melt when heated to 210 ± 2ºC when subjected to differential scanning calorimetry analysis.

117. The salt of S-indobufen according to claim 1, which is a S-indobufen lysine salt; wherein the S-indobufen lysine salt is a lysine salt Type C; wherein the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2 theta (°2Q) of 10.0° ± 0.2°, 16.8° ± 0.2°, 23.6° ± 0.2°; or, wherein the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2 theta (°2Q) of 12.1° ± 0.2°, 20.1° ± 0.2°, 24.9° ± 0.2°; or, wherein the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at diffraction angles 2 theta (°2Q) of 6.2° ± 0.2°, 16.1° ± 0.2°, 18.7° ± 0.2°.

118. The salt of S-indobufen according to claim 1, which is a S-indobufen lysine salt; wherein the S-indobufen lysine salt is a lysine salt Type C; and wherein the X-ray powder diffraction pattern of the lysine salt Type C has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2 theta (°2Q) of 6.2° ± 0.2°, 10.0° ± 0.2°, 12.1° ± 0.2°, 16.1° ± 0.2°, 16.8° ± 0.2°, 18.7° ± 0.2°, 20.1° ± 0.2°, 23.6° ± 0.2°, 24.9° ± 0.2°.

119. The salt of S-indobufen according to claim 1, wherein the X-ray powder diffraction pattern of the lysine salt Type C is substantially as shown in FIG.

72.

120. The salt of S-indobufen according to claim 1, which is a S-indobufen lysine salt; wherein the S-indobufen lysine salt is a lysine salt Type D; wherein the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2 theta (°2Q) of 6.9° ± 0.2°, 10.3° ± 0.2°, 21.8° ± 0.2°; or, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2Q of 13.7°±0.2°, 19.2°±0.2°, 24.7°±0.2°; or, the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2Q of 5.0°±0.2°, 17.2°±0.2°, 20.4°±0.2°.

121. The salt of S-indobufen according to claim 1, which is S-indobufen lysine salt; the S-indobufen lysine salt is lysine salt Type D; the X-ray powder diffraction pattern of the lysine salt Type D has characteristic peaks at diffraction angles 2Q of any 4, or 5, or 6, or 7, or 8, or 9 of 5.0°±0.2°, 6.9°±0.2°, 10.3°±0.2°, 13.7°±0.2°, 17.2°±0.2°, 19.2°±0.2°, 20.4°±0.2°, 21.8°±0.2°, 24.7°±0.2°.

122. The salt of S-indobufen according to claim 120 or 121, wherein the molar ratio of S-indobufen to lysine in the S-indobufen lysine salt is 0.8-1.

4.

123. The salt of S-indobufen according to claim 120 or 121, wherein the X-ray powder diffraction pattern of the lysine salt Type D is substantially as shown in FIG.

73.

124. The salt of S-indobufen according to claim 120 or 121, wherein the lysine salt Type D has a mass loss gradient of 4.11±0.2% when heated to 150±2ºC when subjected to thermogravimetric analysis; or, the lysine salt Type D begins to melt when heated to 205±2ºC when subjected to differential scanning calorimetry analysis.

125. The salt of S-indobufen according to claim 1, which is S-indobufen betaine salt; the S-indobufen betaine salt is betaine salt Type A; the X-ray powder diffraction pattern of the betaine salt Type A has characteristic peaks at diffraction angles 2Q of 10.1°±0.2°, 12.2°±0.2°, 19.4°±0.2°; or, the X-ray powder diffraction pattern of the betaine salt Type A has characteristic peaks at diffraction angles 2Q of 14.8°±0.2°, 17.8°±0.2°, 25.9°±0.2°; or, the X-ray powder diffraction pattern of the betaine salt Type A has characteristic peaks at diffraction angles 2Q of 19.9°±0.2°, 20.4°±0.2°, 28.8°±0.2°.

126. The salt of S-indoxamine of claim 1, which is S-indoxamine betaine salt; the S-indoxamine betaine salt is betaine salt Type A; the X-ray powder diffraction pattern of the betaine salt Type A has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2Q of 10.1°±0.2°, 12.2°±0.2°, 14.8°±0.2°, 17.8°±0.2°, 19.4°±0.2°, 19.9°±0.2°, 20.4°±0.2°, 25.9°±0.2°, 28.8°±0.2°.

127. The salt of S-indoxamine of claim 125 or 126, the X-ray powder diffraction pattern of the betaine salt Type A is substantially as shown in FIG.

76.

128. The salt of S-indoxamine of claim 1, which is S-indoxamine betaine salt; the S-indoxamine betaine salt is betaine salt Type B; the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2Q of 6.6°±0.2°, 16.4°±0.2°, 22.7°±0.2°; or, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2Q of 7.1°±0.2°, 9.0°±0.2°, 11.5°±0.2°; or, the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at diffraction angles 2Q of 10.0°±0.2°, 15.4°±0.2°, 23.6°±0.2°.

129. The salt of S-indoxamine of claim 1, which is S-indoxamine betaine salt; the S-indoxamine betaine salt is betaine salt Type B; the X-ray powder diffraction pattern of the betaine salt Type B has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of diffraction angles 2Q of 6.6°±0.2°, 7.1°±0.2°, 9.0°±0.2°, 10.0°±0.2°, 11.5°±0.2°, 15.4°±0.2°, 16.4°±0.2°, 22.7°±0.2°, 23.6°±0.2°.

130. The salt of S-indoxamine of claim 128 or 129, the X-ray powder diffraction pattern of the betaine salt Type B is substantially as shown in FIG.

77.

131. The salt of S-indoxamine of claim 1, which is S-indoxamine betaine salt; the S-indoxamine betaine salt is betaine salt Type C; the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2Q of 6.8°±0.2°, 11.1°±0.2°, 19.4°±0.2°; the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2Q of 6.8°±0.2°, 11.1°±0.2°, 19.4°±0.2°; or, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2Q of 4.7°±0.2°, 14.9°±0.2°, 25.0°±0.2°; or, the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2Q of 17.0°±0.2°, 22.1°±0.2°, 26.1°±0.2°.

132. The salt of S-indobufen according to claim 1, which is a betaine salt of S-indobufen; the betaine salt of S-indobufen is a betaine salt Type C; the X-ray powder diffraction pattern of the betaine salt Type C has characteristic peaks at diffraction angles 2Q of any 4, or 5, or 6, or 7, or 8, or 9 of 4.7°±0.2°, 6.8°±0.2°, 11.1°±0.2°, 14.9°±0.2°, 17.0°±0.2°, 19.4°±0.2°, 22.1°±0.2°, 25.0°±0.2°, 26.1°±0.2°.

133. The salt of S-indobufen according to claim 131 or 132, wherein the X-ray powder diffraction pattern of the betaine salt Type C is substantially as shown in Figure 78.

134. The salt of S-indobufen according to claim 131 or 132, wherein the betaine salt Type C has a mass loss gradient of 1.93±0.2% when heated to 120 ºC±2 by thermogravimetric analysis; or, the betaine salt Type C begins to melt when heated to 147 ±2ºC by differential scanning calorimetry analysis.

135. The salt of S-indobufen according to any one of claims 125, 126, 128, 129, 131, 132, wherein the molar ratio of S-indobufen to betaine in the betaine salt is 0.8~1.

2.

136. The salt of S-indobufen according to claim 1, which is a diethylamine salt of S-indobufen; the diethylamine salt of S-indobufen is a diethylamine salt Type A; the X-ray powder diffraction pattern of the diethylamine salt Type A has characteristic peaks at diffraction angles 2Q of 6.3°±0.2°, 11.6°±0.2°, 12.7°±0.2°; or, the X-ray powder diffraction pattern of the diethylamine salt Type A has characteristic peaks at diffraction angles 2Q of 14.9°±0.2°, 18.5°±0.2°, 22.4°±0.2°; or, the X-ray powder diffraction pattern of the diethylamine salt Type A has characteristic peaks at diffraction angles 2Q of 7.4°±0.2°, 17.1°±0.2°, 24.0°±0.2°.

137. The salt of S-indoxamine of claim 1, which is S-indoxamine diethylamine salt; the S-indoxamine diethylamine salt is diethylamine salt Type A; the diethylamine salt Type A has an X-ray powder diffraction pattern with peaks at any 4, or 5, or 6, or 7, or 8, or 9 of 2-theta = 6.3°±0.2°, 7.4°±0.2°, 11.6°±0.2°, 12.7°±0.2°, 14.9°±0.2°, 17.1°±0.2°, 18.5°±0.2°, 22.4°±0.2°, 24.0°±0.2°.

138. The salt of S-indoxamine of claim 136 or 137, wherein the molar ratio of S-indoxamine to diethylamine in the diethylamine salt is 0.8-1.

2.

139. The salt of S-indoxamine of claim 136 or 137, wherein the X-ray powder diffraction pattern of the diethylamine salt Type A is substantially as shown in FIG.

81.

140. The salt of S-indoxamine of claim 136 or 137, wherein the diethylamine salt Type A has a mass loss gradient of 13.83±0.2% when heated to 125±2 °C and a mass loss gradient of 6.91±0.2% when heated to 160±2 °C when subjected to thermogravimetric analysis; or, the diethylamine salt Type A begins to melt when heated to 163±2 °C when subjected to differential scanning calorimetry analysis.

141. The salt of S-indoxamine of claim 1, which is S-indoxamine proline co-crystal; the S-indoxamine proline co-crystal is proline co-crystal Type A; the proline co-crystal Type A has an X-ray powder diffraction pattern with peaks at 2-theta = 5.6°±0.2°, 8.4°±0.2°, 20.3°±0.2°; or, the proline co-crystal Type A has an X-ray powder diffraction pattern with peaks at 2-theta = 6.2°±0.2°, 7.4°±0.2°, 13.4°±0.2°; or, the proline co-crystal Type A has an X-ray powder diffraction pattern with peaks at 2-theta = 19.7°±0.2°, 22.2°±0.2°, 23.4°±0.2°.

142. The salt of S-indoxamine of claim 1, which is S-indoxamine proline co-crystal; the S-indoxamine proline co-crystal is proline co-crystal Type A; the proline co-crystal Type A has an X-ray powder diffraction pattern with peaks at any 4, or 5, or 6, or 7, or 8, or 9 of 2-theta = 5.6°±0.2°, 6.2°±0.2°, 7.4°±0.2°, 8.4°±0.2°, 13.4°±0.2°, 19.7°±0.2°, 20.3°±0.2°, 22.2°±0.2°, 23.4°±0.2°. ​ ​ ​ ​ 143. The salt of S-indobufen of claim 141 or 142, wherein the X-ray powder diffraction pattern of the Proline Co-crystal Type A is substantially as shown in FIG.

84.

144. The salt of S-indobufen of claim 141 or 142, wherein the Proline Co-crystal Type A has a mass loss gradient of 0.10 ± 0.2% when heated to 120 ± 2ºC when subjected to thermogravimetric analysis; or, the Proline Co-crystal Type A begins to melt at 169 ± 2ºC when subjected to differential scanning calorimetry analysis.

145. The salt of S-indobufen of claim 1, wherein the salt of S-indobufen is S- indobufen Proline Co-crystal; and the S-indobufen Proline Co-crystal is Proline Co-crystal Type B; the X-ray powder diffraction pattern of the Proline Co-crystal Type B has characteristic peaks at diffraction angles 2 theta (°2Q) of 5.1° ± 0.2°, 18.1° ± 0.2°, 19.6° ± 0.2°; or, the X-ray powder diffraction pattern of the Proline Co-crystal Type B has characteristic peaks at diffraction angles 2 theta (°2Q) of 15.2° ± 0.2°, 19.0° ± 0.2°, 25.7° ± 0.2°; or, the X-ray powder diffraction pattern of the Proline Co-crystal Type B has characteristic peaks at diffraction angles 2 theta (°2Q) of 10.2° ± 0.2°, 24.2° ± 0.2°, 24.9° ± 0.2°.

146. The salt of S-indobufen of claim 1, wherein the salt of S-indobufen is S- indobufen Proline Co-crystal; and the S-indobufen Proline Co-crystal is Proline Co-crystal Type B; and the X-ray powder diffraction pattern of the Proline Co-crystal Type B has characteristic peaks at any 4, or 5, or 6, or 7, or 8, or 9 of the diffraction angles 2 theta (°2Q) of 5.1° ± 0.2°, 10.2° ± 0.2°, 15.2° ± 0.2°, 18.1° ± 0.2°, 19.0° ± 0.2°, 19.6° ± 0.2°, 24.2° ± 0.2°, 24.9° ± 0.2°, 25.7° ± 0.2°.

147. The salt of S-indobufen of claim 1, wherein the X-ray powder diffraction pattern of the Proline Co-crystal Type B is substantially as shown in FIG.

87.

148. The salt of S-indobufen of any one of claims 141, 142, 145, or 146, wherein the molar ratio of S-indobufen to proline in the Proline Co-crystal is 0.8 to 1.

2.

149. The salt of S-indobufen of claim 1, wherein the salt of S-indobufen is S- indobufen Hexadecylamine Salt; and the S-indobufen Hexadecylamine Salt is Hexadecylamine Salt Type A; the X-ray powder diffraction pattern of the Hexadecylamine Salt Type A has characteristic peaks at diffraction angles 2 theta (°2Q) of 4.9° ± 0.2°, 8.3° ± 0.2°, 12.1° ± 0.2°; or, the X-ray powder diffraction pattern of the hexadecylamine salt Type A has characteristic peaks at diffraction angles 2Q of 9.8°±0.2°, 14.8°±0.2°, 20.9°±0.2°; or, the X-ray powder diffraction pattern of the hexadecylamine salt Type A has characteristic peaks at diffraction angles 2Q of 5.6°±0.2°, 7.4°±0.2°, 22.3°±0.2°.

150. The salt of S-indobufen according to claim 1, which is S-indobufen hexadecylamine salt; the S-indobufen hexadecylamine salt is hexadecylamine salt Type A; The X-ray powder diffraction pattern of the hexadecylamine salt Type A has characteristic peaks at diffraction angles 2Q of any 4, or 5, or 6, or 7, or 8, or 9 of 4.9°±0.2°, 5.6°±0.2°, 7.4°±0.2°, 8.3°±0.2°, 9.8°±0.2°, 12.1°±0.2°, 14.8°±0.2°, 20.9°±0.2°, 22.3°±0.2°.

151. The salt of S-indobufen according to claim 149 or 150, wherein the molar ratio of S-indobufen to hexadecylamine in the hexadecylamine salt is 1.5-1.

9.

152. The salt of S-indobufen according to claim 149 or 150, wherein the X-ray powder diffraction pattern of the hexadecylamine salt Type A is substantially as shown in Figure 88.

153. The salt of S-indobufen according to claim 149 or 150, wherein the hexadecylamine salt Type A has a mass loss gradient of 2.23±0.2% when heated to 120±2ºC when subjected to thermogravimetric analysis; or, has an endothermic peak when heated to 64±2ºC and begins to melt when heated to 169±2ºC when subjected to differential scanning calorimetric analysis.

154. A pharmaceutical composition comprising the salt of S-indobufen according to any one of claims 1-153, and one or more pharmaceutically acceptable carriers.

155. Use of the salt of S-indobufen according to any one of claims 1-153 in the preparation of a medicament for the prevention and / or treatment of anti-platelet diseases.

156. Use of the salt of S-indobufen according to any one of claims 1-153 in the preparation of a medicament for the prevention and / or treatment of diseases caused by arteriosclerosis, ischemic cardiovascular diseases, ischemic cerebrovascular diseases, venous thrombosis, or for preventing thrombosis during hemodialysis.

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