Polymorphic form of sGC agonist and preparation method and application thereof

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a polymorphic form of an sGC agonist as well as a preparation method and application of the polymorphic form. The polymorphic form of the sGC agonist is a polymorphic form of a compound I. The polymorphic form of the compound I comprises a crystal form I, a crystal form II, a crystal form III, a crystal form IV, a crystal form V, a crystal form VI, a crystal form VII, a crystal form VIII, a crystal form IX, a crystal form X, a crystal form XI, a crystal form XII, a crystal form XIII, a crystal form XIV, a crystal form XV, a crystal form XVI, a crystal form XVII, a crystal form XVIII, a crystal form XIX, a crystal form XX, a crystal form XXI, a crystal form XXII and a crystal form XXIII. The invention provides the polymorphic form of the sGC agonist LXH-1211, provides technical guarantee for subsequent research and development of drugs and maintenance of consistency of pharmacokinetic and pharmacokinetic properties of the drugs, and also can provide technical support for subsequent industrial production of drugs with specific crystal forms.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a polymorph of an sGC agonist and a preparation method and application thereof. Background Art

[0002] Pulmonary arterial hypertension (PAH) is a highly lethal pulmonary vascular occlusive disease, clinically manifested by progressive increases in pulmonary artery pressure and pulmonary vascular resistance, increased right ventricular afterload, and ultimately right heart failure or even death. Although traditional PAH treatment drugs can improve the survival rate of patients to a certain extent, traditional treatment drugs can only dilate blood vessels to "treat the symptoms" but not the "root cause", and there are drug resistance and side effects such as systemic hypotension. Therefore, the development of PAH targeted treatment drugs is still urgently needed in clinical practice.

[0003] Riociguat is the first soluble guanylate cyclase (sGC) agonist successfully developed by Bayer Pharmaceuticals in Germany. In 2013, the US FDA approved Riociguat for the treatment of chronic thromboembolic pulmonary hypertension and arterial pulmonary hypertension. Riociguat solves the problem of poor long-term prognosis of traditional drugs, but it can only "treat the symptoms" and its vasodilator effect is too strong, which will cause mild systemic hypotension in patients. At present, Riociguat has not been listed in China. With the increasing number of patients with pulmonary hypertension, the search for new drugs for the treatment of pulmonary hypertension that can both "treat the symptoms" as sGC agonists and "treat the root cause" by inhibiting AMPK has attracted more and more attention.

[0004] LXH-1211, chemical name: 2-(3-methyl-1-phenyl-6-((2-methyl)benzyloxy)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrimidine-4,6-diamine, is a sGC agonist drug. Pharmacological data show that the drug has good anti-pulmonary artery smooth muscle cell proliferation activity, which is stronger than the positive control drug Riociguat; while the vasodilator effect is weaker than the positive control drug Riociguat. The above results indicate that LXH-1211 will have the potential to overcome the systemic hypotension caused by Riociguat in the treatment of PAH while having anti-pulmonary hypertension activity, thereby achieving the effect of "treating both the symptoms and the root cause". At the same time, the drug also exhibits a certain anti-pulmonary fibrosis effect. So far, there is no report on the crystal form of LXH-1211. Summary of the invention

[0005] The purpose of the present invention is to provide a polymorph of a sGC agonist to provide technical support for subsequent drug development and industrial production; the present invention also provides a preparation method and application of the polymorph of a sGC agonist.

[0006] The polymorph of the sGC agonist of the present invention is a polymorph of Compound I, and the structural formula of Compound I is as follows:

[0007]

[0008] The polymorphic forms of Compound I include Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, Form X, Form XI, Form XII, Form XIII, Form XIV, Form XV, Form XVI, Form XVII, Form XVIII, Form XIX, Form XX, Form XXI, Form XXII and Form XXIII.

[0009] The X-ray powder diffraction spectrum of Form I expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0108°, 9.5975°, 11.8529°, 13.1094°, 18.1392°, 18.9765°, 19.6892°, 22.9121°, 24.5164°, and 27.2046°;

[0010] Preferably, the X-ray powder diffraction spectrum of Form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0108°, 9.2291°, 9.5975°, 10.7891°, 11.8529°, 13.1094°, 16.2972°, 17.5452°, 18.1392°, 18.4776°, 18.9765°, 19.6892°, 20.1756°, 20.5641°, 22.7598°, 22.9121°, 23.8564°, 24.5164°, 27.2046°, and 27.7852°;

[0011] Preferably, the X-ray powder diffraction spectrum of Form I represented by a diffraction angle of 2θ±0.2° is 9.0108°, 9.2291°, 9.5975°, 9.8422°, 10.5397°, 10.7891°, 11.8529°, 12.3461°, 13.1094°, 15.3009°, 15.5385°, 15.9365°, 16.2972°, 16.5676°, 16.7064°, 17.5452°, 18.1392°, 18.4776°, 1 There are diffraction peaks at 8.9765°, 19.6892°, 20.1756°, 20.5641°, 20.7731°, 21.072°, 21.6182°, 22.1326°, 22.7598°, 22.9121°, 23.8564°, 24.2325°, 24.5164°, 26.3531°, 26.9224°, 27.2046°, 27.4413°, 27.7852°, 28.2752°, 29.6917°, and 30.5549°;

[0012] Preferably, the X-ray powder diffraction spectrum of Form I represented by a diffraction angle of 2θ±0.2° is 3.9655°, 6.573°, 8.4859°, 9.0108°, 9.2291°, 9.5975°, 9.8422°, 10.5397°, 10.7891°, 11.8529°, 12.3461°, 13.1094°, 14.0714°, 14.9594°, 15.3009°, 15.5385°, 15.9365°, 16.2972°, 16.5676°, 16.7064°, 17.5452°, 18.1392°, 18.4776°, 18.9765° There are diffraction peaks at 19.6892°, 20.1756°, 20.5641°, 20.7731°, 21.072°, 21.6182°, 22.1326°, 22.7598°, 22.9121°, 23.8564°, 24.2325°, 24.5164°, 25.0865°, 25.4534°, 26.3531°, 26.9224°, 27.2046°, 27.4413°, 27.7852°, 28.2752°, 28.9362°, 29.2808°, 29.6917°, 30.5549°, 31.3961°, and 32.1292°;

[0013] Preferably, Form I has one or more of the following characteristics:

[0014] (1) The TGA curve of Form I shows a weight loss of 9.65±1% at 180.0±3°C;

[0015] (2) The TGA curve of Form I has a decomposition endothermic peak starting point at 291.5±3°C;

[0016] (3) The DSC curve of Form I has a desolvation endothermic peak at 132.1±3°C;

[0017] (4) The DSC curve of Form I has a melting endothermic peak at 222.9±3℃.

[0018] The X-ray powder diffraction spectrum of Form II expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.118°, 10.5628°, 16.2631°, 16.7055°, 18.2844°, 18.6888°, 23.2135°, 23.7283°, 24.7652°, and 24.9396°;

[0019] Preferably, the X-ray powder diffraction spectrum of Form II represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.118°, 9.8184°, 10.5628°, 12.5988°, 13.6591°, 15.2348°, 15.4213°, 16.2631°, 16.7055°, 18.2844°, 18.6888°, 18.9162°, 19.6482°, 21.7878°, 22.0415°, 23.2135°, 23.7283°, 24.7652°, 24.9396°, 25.243°, and 25.8567°;

[0020] Preferably, the X-ray powder diffraction spectrum of Form II represented by a diffraction angle of 2θ±0.2° is 7.934°, 9.118°, 9.2902°, 9.8184°, 10.5628°, 10.9728°, 12.5988°, 13.6591°, 15.2348°, 15.4213°, 16.2631°, 16.7055°, 18.0402°, 18.2844°, 18.6888°, 18.9162°, 19.124 There are diffraction peaks at 4°, 19.4049°, 19.6482°, 20.0337°, 20.3903°, 21.4219°, 21.7878°, 22.0415°, 22.3281°, 22.8857°, 23.2135°, 23.7283°, 24.7652°, 24.9396°, 25.243°, 25.8567°, 26.378°, 27.1598°, 27.5634°, and 31.3168°;

[0021] Preferably, the X-ray powder diffraction spectrum of Form II represented by a diffraction angle of 2θ±0.2° is 7.934°, 9.118°, 9.2902°, 9.8184°, 10.5628°, 10.9728°, 12.5988°, 13.6591°, 15.2348°, 15.4213°, 16.2631°, 16.7055°, 18.0402°, 18.2844°, 18.6888°, 18.9162°, 19.1244°, 19.4049°, 19.648 There are diffraction peaks at 2°, 20.0337°, 20.3903°, 21.4219°, 21.7878°, 22.0415°, 22.3281°, 22.8857°, 23.2135°, 23.7283°, 24.7652°, 24.9396°, 25.243°, 25.8567°, 26.378°, 27.1598°, 27.5634°, 29.4736°, 31.3168°, 32.1421°, 32.9129°, and 38.1754°;

[0022] Preferably, Form II has one or more of the following characteristics:

[0023] (1) The TGA curve of Form II shows a weight loss of 1.06±1% at 150.0±3°C;

[0024] (2) The TGA curve of Form II has a decomposition endothermic peak starting point at 284.0±3°C;

[0025] (3) The DSC curve of Form II has a desolvation endothermic peak at 201.9±3°C;

[0026] (4) The DSC curve of Form II has a melting endothermic peak at 225.1±3°C.

[0027] The X-ray powder diffraction spectrum of Form III expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9297°, 9.8289°, 16.6539°, 17.8685°, 18.1427°, 19.5768°, 21.5442°, 21.7443°, 24.7395°, and 25.6847°;

[0028] Preferably, the X-ray powder diffraction spectrum of Form III represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9297°, 9.8289°, 14.9608°, 15.7384°, 16.6539°, 17.8685°, 18.1427°, 19.5768°, 21.5442°, 21.7443°, 22.6617°, 24.7395°, 25.6847°, and 26.9319°;

[0029] Preferably, the X-ray powder diffraction spectrum of Form III represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9297°, 9.8289°, 14.6479°, 14.9608°, 15.7384°, 16.6539°, 17.8685°, 18.1427°, 19.5768°, 21.5442°, 21.7443°, 22.6617°, 24.7395°, 25.6847°, 26.9319°, 28.1208°, and 29.837°;

[0030] Preferably, the X-ray powder diffraction spectrum of Form III represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9297°, 9.8289°, 11.9127°, 14.6479°, 14.9608°, 15.7384°, 16.6539°, 17.8685°, 18.1427°, 19.5768°, 21.5442°, 21.7443°, 22.6617°, 24.7395°, 25.6847°, 26.9319°, 28.1208°, 29.837°, 31.5086°, 33.166°, and 36.3974°;

[0031] Preferably, Form III has one or more of the following characteristics:

[0032] (1) The TGA curve of Form III shows a weight loss of 12.87±1% at 160.0±3°C;

[0033] (2) The TGA curve of Form III has a decomposition endothermic peak starting point at 273.7±3°C;

[0034] (3) The DSC curve of Form III has a desolvation endothermic peak at 135.6±3°C;

[0035] (4) The DSC curve of Form III has a melting endothermic peak at 222.5±3°C.

[0036] The X-ray powder diffraction spectrum of Form IV expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.2951°, 17.9978°, 18.5726°, 19.7368°, 21.6855°, and 25.2649°;

[0037] Preferably, the X-ray powder diffraction spectrum of Form IV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.2951°, 10.3942°, 16.6591°, 17.9978°, 18.5726°, 19.7368°, 20.8526°, 21.6855°, 23.8965°, 25.2649°, and 26.2148°;

[0038] Preferably, the X-ray powder diffraction spectrum of Form IV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.2931°, 9.2951°, 10.3942°, 14.5845°, 16.6591°, 17.9978°, 18.5726°, 19.7368°, 20.8526°, 21.6855°, 23.8965°, 25.2649°, and 26.2148°;

[0039] Preferably, the X-ray powder diffraction spectrum of Form IV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.2931°, 9.2951°, 10.3942°, 14.5845°, 16.6591°, 17.9978°, 18.5726°, 19.7368°, 20.8526°, 21.6855°, 23.8965°, 25.2649°, 26.2148°, and 29.7988°;

[0040] Preferably, Form IV has one or more of the following characteristics:

[0041] (1) The TGA curve of Form IV shows a weight loss of 7.70±1% at 160.0±3°C;

[0042] (2) The TGA curve of Form IV has a decomposition endothermic peak starting point at 281.1±3°C;

[0043] (3) The DSC curve of Form IV has a desolvation endothermic peak at 114.8±3°C;

[0044] (4) The DSC curve of Form IV has a melting endothermic peak at 224.7±3°C.

[0045] The X-ray powder diffraction spectrum of Form V represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0358°, 9.5888°, 9.8806°, 15.3988°, 18.12°, 19.3591°, 20.0225°, 21.8772°, 22.9544°, 23.1765°, 23.9432°, and 27.8035°;

[0046] Preferably, the X-ray powder diffraction spectrum of Form V represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0358°, 9.5888°, 9.8806°, 15.3988°, 17.4867°, 18.12°, 19.3591°, 20.0225°, 20.5607°, 21.8772°, 22.9544°, 23.1765°, 23.5735°, 23.9432°, 24.6797°, 25.3441°, 26.2773°, 27.3778°, and 27.8035°;

[0047] Preferably, the X-ray powder diffraction spectrum of Form V represented by a diffraction angle of 2θ±0.2° is 9.0358°, 9.5888°, 9.8806°, 11.361°, 12.2799°, 12.8514°, 13.2758°, 15.3988°, 16.2755°, 17.1285°, 17.4867°, 18.12°, 19.3591 There are diffraction peaks at 20.0225°, 20.5607°, 21.8772°, 22.9544°, 23.1765°, 23.5735°, 23.9432°, 24.6797°, 25.3441°, 26.2773°, 27.3778°, 27.8035°, 28.8749°, 30.8579°, and 32.8505°;

[0048] Preferably, the X-ray powder diffraction spectrum of Form V represented by a diffraction angle of 2θ±0.2° is 9.0358°, 9.5888°, 9.8806°, 11.361°, 12.2799°, 12.8514°, 13.2758°, 13.9999°, 15.3988°, 16.2755°, 17.1285°, 17.4867°, 18.12°, 19.3591 There are diffraction peaks at 20.0225°, 20.5607°, 21.8772°, 22.9544°, 23.1765°, 23.5735°, 23.9432°, 24.6797°, 25.3441°, 26.2773°, 27.3778°, 27.8035°, 28.8749°, 30.8579°, 32.8505°, and 34.8296°;

[0049] Preferably, Form V has one or more of the following characteristics:

[0050] (1) The TGA curve of Form V shows a weight loss of 9.41±1% at 150.0±3°C;

[0051] (2) The TGA curve of Form V has a decomposition endothermic peak at 275.4±3°C;

[0052] (3) The DSC curve of Form V has a desolvation endothermic peak at 114.4±3°C;

[0053] (4) The DSC curve of Form V has a melting endothermic peak at 222.1±3℃.

[0054] The X-ray powder diffraction spectrum of Form VI expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1268°, 9.4721°, 11.0475°, 14.0327°, 18.2534°, 19.3437°, 20.831°, 23.3618°, 23.895°, 24.2089°, and 24.4642°;

[0055] Preferably, the X-ray powder diffraction spectrum of Form VI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1268°, 9.4721°, 11.0475°, 14.0327°, 14.508°, 15.7801°, 16.1212°, 18.2534°, 19.3437°, 20.831°, 21.9229°, 22.6521°, 23.3618°, 23.895°, 24.2089°, 24.4642°, and 26.6075°;

[0056] Preferably, the X-ray powder diffraction spectrum of Form VI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1268°, 9.4721°, 11.0475°, 14.0327°, 14.508°, 15.6786°, 15.7801°, 16.1212°, 18.2534°, 18.6444°, 18.9682°, 19.3437°, 20.831°, 21.9229°, 22.6521°, 23.3618°, 23.895°, 24.2089°, 24.4642°, 26.6075°, 27.1937°, and 27.5809°;

[0057] Preferably, the X-ray powder diffraction spectrum of Form VI represented by a diffraction angle of 2θ±0.2° is 9.1268°, 9.4721°, 11.0475°, 12.02°, 14.0327°, 14.508°, 15.6786°, 15.7801°, 16.1212°, 18.2534°, 18.6444°, 18.9682°, 19.34 There are diffraction peaks at 37°, 20.831°, 21.9229°, 22.6521°, 23.3618°, 23.895°, 24.2089°, 24.4642°, 26.6075°, 27.1937°, 27.5809°, 28.6731°, 29.1871°, 32.192°, 33.2597°, and 35.0832°;

[0058] Preferably, Form VI has one or more of the following characteristics:

[0059] (1) The TGA curve of Form VI shows a weight loss of 9.82±1% at 150.0±3°C;

[0060] (2) The TGA curve of Form VI has a decomposition endothermic peak at 279.0±3°C;

[0061] (3) The DSC curve of Form VI has a desolvation endothermic peak at 129.6±3°C;

[0062] (4) The DSC curve of Form VI has a melting endothermic peak at 224.2±3°C.

[0063] The X-ray powder diffraction spectrum of Form VII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 4.6919°, 9.3635°, 14.0205°, 18.7694°, and 22.6999°;

[0064] Preferably, the X-ray powder diffraction spectrum of Form VII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.6919°, 9.3635°, 14.0205°, 15.3932°, 16.095°, 18.7694°, 22.6999°, and 23.3297°;

[0065] Preferably, the X-ray powder diffraction spectrum of Form VII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.6919°, 8.4329°, 9.3635°, 14.0205°, 15.3932°, 16.095°, 17.2857°, 18.7694°, 20.9648°, 22.6999°, 23.3297°, and 27.0515°;

[0066] Preferably, the X-ray powder diffraction spectrum of Form VII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.6919°, 8.4329°, 9.3635°, 14.0205°, 15.3932°, 16.095°, 17.2857°, 18.7694°, 20.9648°, 22.6999°, 23.3297°, 27.0515°, 29.8293°, and 32.4716°;

[0067] Preferably, Form VII has one or more of the following characteristics:

[0068] (1) The TGA curve of Form VII shows a weight loss of 6.77±1% at 150.0±3°C;

[0069] (2) The TGA curve of Form VII has a decomposition endothermic peak at 286.8±3°C;

[0070] (3) The DSC curve of Form VII has a desolvation endothermic peak at 117.4±3°C;

[0071] (4) The DSC curve of Form VII has a melting endothermic peak at 223.3±3°C.

[0072] The X-ray powder diffraction spectrum of Form VIII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8902°, 9.818°, 15.9516°, 16.5412°, 17.851°, 19.5499°, 20.0096°, 21.4687°, 24.3685°, and 25.3691°;

[0073] Preferably, the X-ray powder diffraction spectrum of Form VIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8902°, 9.818°, 15.9516°, 16.5412°, 17.851°, 18.2837°, 19.5499°, 20.0096°, 21.4687°, 21.8612°, 22.6366°, 24.3685°, 25.3691°, 25.6532°, 26.8742°, and 28.063°;

[0074] Preferably, the X-ray powder diffraction spectrum of Form VIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8902°, 9.818°, 14.8678°, 15.9516°, 16.5412°, 17.851°, 18.2837°, 18.7011°, 19.5499°, 20.0096°, 21.4687°, 21.8612°, 22.6366°, 23.9934°, 24.3685°, 24.8029°, 25.3691°, 25.6532°, 26.8742°, and 28.063°;

[0075] Preferably, the X-ray powder diffraction spectrum of Form VIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8902°, 9.818°, 14.4868°, 14.8678°, 15.9516°, 16.5412°, 17.851°, 18.2837°, 18.7011°, 19.5499°, 20.0096°, 21.4687°, 21.8612°, 22.6366°, 23.9934°, 24.3685°, 24.8029°, 25.3691°, 25.6532°, 26.8742°, 28.063°, 32.3583°, and 33.2506°;

[0076] Preferably, Form VIII has one or more of the following characteristics:

[0077] (1) The TGA curve of Form VIII shows a weight loss of 12.97±1% at 150.0±3°C;

[0078] (2) The TGA curve of Form VIII has a decomposition endothermic peak at 294.7±3°C;

[0079] (3) The DSC curve of Form VIII has a desolvation endothermic peak at 121.3±3°C;

[0080] (4) The DSC curve of Form VIII has a melting endothermic peak at 226.0±3°C.

[0081] The X-ray powder diffraction spectrum of Form IX expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.6297°, 10.1401°, 10.8559°, 15.807°, 16.46°, 19.0276°, 19.3101°, 20.3323°, 20.4808°, 21.8649°, 22.9775°, 23.8504°, and 24.3408°;

[0082] Preferably, the X-ray powder diffraction spectrum of Form IX represented by a diffraction angle of 2θ±0.2° is 9.6297°, 10.1401°, 10.8559°, 15.0787°, 15.807°, 16.46°, 19.0276°, 19.3101°, 20.3323°, 20.4808°, 21.8649°, There are diffraction peaks at 22.1377°, 22.4816°, 22.9775°, 23.3786°, 23.8504°, 24.3408°, 24.8941°, 25.3824°, 25.685°, 26.9466°, 27.912°, 28.2891°, 29.6722°, and 29.885°;

[0083] Preferably, the X-ray powder diffraction spectrum of Form IX represented by a diffraction angle of 2θ±0.2° is 9.6297°, 10.1401°, 10.8559°, 13.8649°, 15.0787°, 15.807°, 16.46°, 17.5469°, 18.0559°, 19.0276°, 19.3101°, 20.3323°, 20.4808°, 21.8649°, 22.1 There are diffraction peaks at 377°, 22.4816°, 22.9775°, 23.3786°, 23.8504°, 24.3408°, 24.8941°, 25.3824°, 25.685°, 26.4906°, 26.9466°, 27.912°, 28.2891°, 29.6722°, 29.885°, 31.0229°, 31.468°, and 31.9828°;

[0084] Preferably, the X-ray powder diffraction spectrum of Form IX represented by a diffraction angle of 2θ±0.2° is 7.8956°, 9.6297°, 10.1401°, 10.8559°, 12.1534°, 13.1811°, 13.8649°, 15.0787°, 15.807°, 16.46°, 17.5469°, 18.0559°, 19.0276°, 19.3101°, 20.3323°, 20.4808°, 21.8649°, 22.1377°, There are diffraction peaks at 22.4816°, 22.9775°, 23.3786°, 23.8504°, 24.3408°, 24.8941°, 25.3824°, 25.685°, 26.4906°, 26.9466°, 27.912°, 28.2891°, 29.6722°, 29.885°, 31.0229°, 31.468°, 31.9828°, 33.1869°, 34.2335°, 36.6216°, and 38.5212°;

[0085] Preferably, Form IX has one or more of the following characteristics:

[0086] (1) The TGA curve of Form IX shows a weight loss of 8.19±1% ​​at 150.0±3°C;

[0087] (2) The TGA curve of Form IX has a decomposition endothermic peak at 273.0±3°C;

[0088] (3) The DSC curve of Form IX has a desolvation endothermic peak at 114.3±3°C;

[0089] (4) The DSC curve of Form IX has a melting endothermic peak at 222.6±3°C.

[0090] The X-ray powder diffraction spectrum of Form X represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0067°, 9.1811°, 9.6511°, 16.4799°, 17.8184°, 18.4803°, 19.3685°, 20.9226°, 21.5952°, 22.1082°, 22.6517°, 24.0245°, 25.5636°, and 30.2049°;

[0091] Preferably, the X-ray powder diffraction spectrum of Form X represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0067°, 9.1811°, 9.6511°, 12.4199°, 13.6572°, 16.4799°, 17.8184°, 18.4803°, 19.3685°, 19.9298°, 20.9226°, 21.5952°, 22.1082°, 22.6517°, 24.0245°, 25.5636°, 26.7415°, 27.8212°, 29.0343°, and 30.2049°;

[0092] Preferably, the X-ray powder diffraction spectrum of Form X represented by a diffraction angle of 2θ±0.2° is 9.0067°, 9.1811°, 9.6511°, 10.4715°, 12.4199°, 13.2215°, 13.6572°, 15.3908°, 15.7063°, 16.4799°, 17.0879°, 17.818 There are diffraction peaks at 4°, 18.4803°, 19.3685°, 19.9298°, 20.9226°, 21.5952°, 22.1082°, 22.6517°, 24.0245°, 25.5636°, 26.7415°, 27.8212°, 29.0343°, 30.2049°, and 31.6775°;

[0093] Preferably, the X-ray powder diffraction spectrum of Form X represented by a diffraction angle of 2θ±0.2° is 9.0067°, 9.1811°, 9.6511°, 10.4715°, 12.4199°, 13.2215°, 13.6572°, 15.3908°, 15.7063°, 16.4799°, 17.0879°, 17.8184°, 18.480 There are diffraction peaks at 3°, 19.3685°, 19.9298°, 20.9226°, 21.5952°, 22.1082°, 22.6517°, 24.0245°, 25.5636°, 26.7415°, 27.8212°, 29.0343°, 30.2049°, 31.6775°, 33.1822°, and 35.4315°;

[0094] Preferably, the crystal form X has one or more of the following characteristics:

[0095] (1) The TGA curve of Form X shows a weight loss of 4.77±1% at 150.0±3°C;

[0096] (2) The TGA curve of Form X has a decomposition endothermic peak at 281.5±3°C;

[0097] (3) The DSC curve of Form X has a desolvation endothermic peak at 119.6±3°C;

[0098] (4) The DSC curve of Form X has a melting endothermic peak at 224.3±3°C.

[0099] The X-ray powder diffraction spectrum of Form XI expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5285°, 8.1617°, 9.1043°, 10.1559°, 13.5418°, 16.6487°, 18.2041°, 19.1824°, 19.6305°, 21.3619°, 22.7723°, 22.909°, 23.7944°, 25.502°, 25.9827°, and 26.2473°;

[0100] Preferably, the X-ray powder diffraction spectrum of Form XI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5285°, 7.3628°, 8.1617°, 9.1043°, 9.4879°, 10.1559°, 13.0572°, 13.3712°, 13.5418°, 16.6487°, 18.2041°, 19.1824°, 19.6305°, 20.3145°, 21.3619°, 22.7723°, 22.909°, 23.7944°, 24.9466°, 25.502°, 25.9827°, and 26.2473°;

[0101] Preferably, the X-ray powder diffraction spectrum of Form XI represented by a diffraction angle of 2θ±0.2° is 5.9933°, 6.5285°, 7.3628°, 7.5638°, 8.1617°, 9.1043°, 9.4879°, 10.1559°, 13.0572°, 13.3712°, 13.5418°, 16.3001°, 16.6487°, 1 There are diffraction peaks at 7.0183°, 17.799°, 18.2041°, 19.1824°, 19.6305°, 20.3145°, 21.3619°, 22.1595°, 22.7723°, 22.909°, 23.7944°, 24.9466°, 25.502°, 25.9827°, 26.2473°, and 27.5388°;

[0102] Preferably, the X-ray powder diffraction spectrum of Form XI represented by a diffraction angle of 2θ±0.2° is 5.9933°, 6.5285°, 7.3628°, 7.5638°, 8.1617°, 9.1043°, 9.4879°, 10.1559°, 10.8344°, 13.0572°, 13.3712°, 13.5418°, 14.4054°, 15.211°, 15.96°, 16.3001°, 16. There are diffraction peaks at 6487°, 17.0183°, 17.799°, 18.2041°, 19.1824°, 19.6305°, 20.3145°, 21.3619°, 22.1595°, 22.7723°, 22.909°, 23.7944°, 24.9466°, 25.502°, 25.9827°, 26.2473°, 27.5388°, 31.9424°, and 36.0309°;

[0103] Preferably, Form XI has one or more of the following characteristics:

[0104] (1) The TGA curve of Form XI shows a weight loss of 6.73±1% at 150.0±3°C;

[0105] (2) The TGA curve of Form XI has a decomposition endothermic peak at 276.4±3°C;

[0106] (3) The DSC curve of Form XI has a desolvation endothermic peak at 103.3±3°C;

[0107] (4) The DSC curve of Form XI has a melting endothermic peak at 222.6±3°C.

[0108] The X-ray powder diffraction spectrum of Form XII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0648°, 17.9771°, 19.4221°, 19.8351°, 22.9163°, and 24.0604°;

[0109] Preferably, the X-ray powder diffraction spectrum of Form XII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0648°, 14.6209°, 16.3618°, 17.9771°, 19.4221°, 19.8351°, 22.9163°, and 24.0604°;

[0110] Preferably, the X-ray powder diffraction spectrum of Form XII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0648°, 14.6209°, 15.2996°, 16.3618°, 17.9771°, 19.4221°, 19.8351°, 22.9163°, and 24.0604°;

[0111] Preferably, the X-ray powder diffraction spectrum of Form XII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0648°, 10.3029°, 14.6209°, 15.2996°, 16.3618°, 17.9771°, 19.4221°, 19.8351°, 22.9163°, 24.0604°, and 27.8066°;

[0112] Preferably, Form XII has one or more of the following characteristics:

[0113] (1) The TGA curve of Form XII shows a weight loss of 7.91±1% at 120.0±3°C;

[0114] (2) The TGA curve of Form XII has a decomposition endothermic peak at 275.4±3°C;

[0115] (3) The DSC curve of Form XII has desolvation endothermic peaks at 97.5±3°C and 145.7±3°C;

[0116] (4) The DSC curve of Form XII has a melting endothermic peak at 222.9±3°C.

[0117] The X-ray powder diffraction spectrum of Form XIII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9947°, 7.9653°, 11.9493°, 13.0858°, 18.0925°, 23.1188°, 24.3969°, 25.2526°, 25.971°, and 26.7208°;

[0118] Preferably, the X-ray powder diffraction spectrum of Form XIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9947°, 7.9653°, 8.9989°, 11.9493°, 13.0858°, 17.1229°, 18.0925°, 23.1188°, 23.7992°, 24.3969°, 25.2526°, 25.971°, 26.7208°, and 28.1045°;

[0119] Preferably, the X-ray powder diffraction spectrum of Form XIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9947°, 7.9653°, 8.9989°, 10.5616°, 11.9493°, 13.0858°, 17.1229°, 18.0925°, 23.1188°, 23.7992°, 24.3969°, 25.2526°, 25.971°, 26.7208°, and 28.1045°;

[0120] Preferably, the X-ray powder diffraction spectrum of Form XIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9947°, 7.9653°, 8.9989°, 10.5616°, 11.9493°, 13.0858°, 15.2983°, 17.1229°, 18.0925°, 23.1188°, 23.7992°, 24.3969°, 25.2526°, 25.971°, 26.7208°, 28.1045°, and 31.1848°;

[0121] Preferably, Form XIII has one or more of the following characteristics:

[0122] (1) The TGA curve of Form XIII shows a weight loss of 2.74±1% at 150.0±3°C;

[0123] (2) The TGA curve of Form XIII has a decomposition endothermic peak at 251.1±3°C;

[0124] (3) The DSC curve of Form XIII has desolvation endothermic peaks at 69.9±3°C and 101.5±3°C;

[0125] (4) The DSC curve of Form XIII has a melting endothermic peak at 221.9±3°C.

[0126] The X-ray powder diffraction spectrum of Form XIV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.746°, 8.9487°, 9.5388°, 14.0763°, 16.3184°, 16.5286°, 17.2373°, 18.3355°, 19.1287°, 19.3844°, 20.1885°, 21.4895°, 23.5043°, 23.8672°, 24.9351°, 25.1009°, 25.3026°, and 26.7261°;

[0127] Preferably, the X-ray powder diffraction spectrum of Form XIV represented by a diffraction angle of 2θ±0.2° is 8.746°, 8.9487°, 9.5388°, 14.0763°, 14.9162°, 16.3184°, 16.5286°, 17.2373°, 17.9255°, 18.3355°, 18.6382°, 18.9497°, 19.1287°, There are diffraction peaks at 19.3844°, 20.1885°, 21.4895°, 21.7479°, 22.6605°, 22.813°, 23.5043°, 23.8672°, 24.9351°, 25.1009°, 25.3026°, 26.1261°, 26.7261°, 31.4344°, 31.8331°, and 33.1575°;

[0128] Preferably, the X-ray powder diffraction spectrum of Form XIV represented by a diffraction angle of 2θ±0.2° is 8.746°, 8.9487°, 9.5388°, 14.0763°, 14.9162°, 15.0777°, 16.3184°, 16.5286°, 17.2373°, 17.5152°, 17.7266°, 17.9255°, 18.3355°, 18.6382°, 18.9497°, 19.1287°, 19.3844°, 19.8064°, 20.1 There are diffraction peaks at 885°, 21.4895°, 21.7479°, 22.6605°, 22.813°, 23.5043°, 23.8672°, 24.9351°, 25.1009°, 25.3026°, 25.708°, 26.1261°, 26.7261°, 27.0206°, 28.8713°, 29.2053°, 29.7983°, 30.142°, 30.4013°, 31.4344°, 31.8331°, and 33.1575°;

[0129] Preferably, the X-ray powder diffraction spectrum of Form XIV represented by a diffraction angle of 2θ±0.2° is 8.746°, 8.9487°, 9.5388°, 14.0763°, 14.9162°, 15.0777°, 16.3184°, 16.5286°, 17.2373°, 17.5152°, 17.7266°, 17.9255°, 18.3355°, 18.6382°, 18.9497°, 19.1287°, 19.3844°, 19.8064°, 20.1885°, 21.4895°, 21.7479°, 22.6605°, 22. There are diffraction peaks at .813°, 23.5043°, 23.8672°, 24.9351°, 25.1009°, 25.3026°, 25.708°, 26.1261°, 26.7261°, 27.0206°, 28.8713°, 29.2053°, 29.7983°, 30.142°, 30.4013°, 31.4344°, 31.8331°, 32.6225°, 33.1575°, 33.985°, 34.8527°, 35.8313°, 36.2587°, 37.138°, 37.74°, and 38.7228°;

[0130] Preferably, Form XIV has one or more of the following characteristics:

[0131] (1) The TGA curve of Form XIV shows a weight loss of 18.92±1% at 200.0±3°C;

[0132] (2) The TGA curve of Form XIV has a decomposition endothermic peak at 287.3±3°C;

[0133] (3) The DSC curve of Form XIV has a desolvation endothermic peak at 144.2±3°C;

[0134] (4) The DSC curve of Form XIV has a melting endothermic peak at 222.5±3°C.

[0135] The X-ray powder diffraction spectrum of Form XV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9849°, 9.7141°, 9.8357°, 15.6953°, 16.302°, 18.0068°, 18.4092°, 19.7077°, 21.1974°, 22.0516°, 23.9004°, and 25.9115°;

[0136] Preferably, the X-ray powder diffraction spectrum of Form XV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9849°, 9.7141°, 9.8357°, 12.518°, 15.6953°, 16.302°, 16.5586°, 18.0068°, 18.4092°, 19.163°, 19.7077°, 21.1974°, 22.0516°, 22.5972°, 23.9004°, 24.5702°, 25.9115°, and 30.0833°;

[0137] Preferably, the X-ray powder diffraction spectrum of Form XV represented by a diffraction angle of 2θ±0.2° is 8.9849°, 9.1887°, 9.7141°, 9.8357°, 10.5106°, 12.518°, 13.5884°, 15.6953°, 16.302°, 16.5586°, 17.287°, 18 There are diffraction peaks at .0068°, 18.4092°, 19.163°, 19.7077°, 20.7121°, 21.1974°, 22.0516°, 22.5972°, 23.9004°, 24.5702°, 25.9115°, 27.714°, 29.2898°, and 30.0833°;

[0138] Preferably, the X-ray powder diffraction spectrum of Form XV represented by a diffraction angle of 2θ±0.2° is 8.9849°, 9.1887°, 9.7141°, 9.8357°, 10.5106°, 10.97°, 12.518°, 13.5884°, 15.6953°, 16.302°, 16.5586°, 17.287°, 18.0068°, 18.4092 There are diffraction peaks at 14.7°, 15.7°, 20.7121°, 21.1974°, 22.0516°, 22.5972°, 23.9004°, 24.5702°, 25.9115°, 27.714°, 29.2898°, 30.0833°, 30.7723°, 31.6746°, 32.683°, and 38.0187°;

[0139] Preferably, Form XV has one or more of the following characteristics:

[0140] (1) The TGA curve of Form XV shows a weight loss of 10.41±1% at 200.0±3°C;

[0141] (2) The TGA curve of Form XV has a decomposition endothermic peak at 270.0±3°C;

[0142] (3) The DSC curve of Form XV has a desolvation endothermic peak at 150.9±3°C;

[0143] (4) The DSC curve of Form XV has a melting endothermic peak at 222.6±3℃.

[0144] The X-ray powder diffraction spectrum of Form XVI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7733°, 10.5581°, 15.6149°, 16.4871°, 18.6864°, 19.121°, 19.5957°, 20.9453°, 21.878°, 22.2877°, 24.2135°, 24.6459°, 26.522°, and 28.023°;

[0145] Preferably, the X-ray powder diffraction spectrum of Form XVI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7733°, 10.5581°, 15.6149°, 16.4871°, 18.6864°, 19.121°, 19.5957°, 20.9453°, 21.5841°, 21.878°, 22.2877°, 22.579°, 23.6036°, 24.2135°, 24.6459°, 25.3263°, 26.522°, 28.023°, and 28.5495°;

[0146] Preferably, the X-ray powder diffraction spectrum of Form XVI represented by a diffraction angle of 2θ±0.2° is 9.7733°, 10.5581°, 10.8953°, 15.6149°, 16.4871°, 18.6864°, 18.8771°, 19.121°, 19.5957°, 20.2442°, 20.9453°, 21.584 There are diffraction peaks at 1°, 21.878°, 22.2877°, 22.579°, 23.0691°, 23.4112°, 23.6036°, 24.2135°, 24.6459°, 25.3263°, 26.17°, 26.522°, 28.023°, 28.5495°, 29.7362°, and 31.6608°;

[0147] Preferably, the X-ray powder diffraction spectrum of Form XVI represented by a diffraction angle of 2θ±0.2° is 9.7733°, 10.5581°, 10.8953°, 14.1974°, 15.6149°, 16.0124°, 16.4871°, 17.279°, 17.6191°, 18.6864°, 18.8771°, 19.121°, 19.5957°, 20.2442°, 20.9453°, 21.584 There are diffraction peaks at 1°, 21.878°, 22.2877°, 22.579°, 23.0691°, 23.4112°, 23.6036°, 24.2135°, 24.6459°, 25.3263°, 26.17°, 26.522°, 28.023°, 28.5495°, 29.7362°, 31.6608°, 32.712°, 33.2065°, 34.4688°, and 37.8656°;

[0148] Preferably, Form XVI has one or more of the following characteristics:

[0149] (1) The TGA curve of Form XVI shows a weight loss of 8.51±1% at 150.0±3°C;

[0150] (2) The TGA curve of Form XVI has a decomposition endothermic peak at 276.9±3°C;

[0151] (3) The DSC curve of Form XVI has a desolvation endothermic peak at 115.7±3°C;

[0152] (4) The DSC curve of Form XVI has a melting endothermic peak at 222.7±3°C.

[0153] The X-ray powder diffraction spectrum of Form XVII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9382°, 9.4506°, 11.7177°, 15.6252°, 17.1262°, 18.9052°, 19.4649°, 20.847°, 21.9599°, and 23.4901°;

[0154] Preferably, the X-ray powder diffraction spectrum of Form XVII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9382°, 9.4506°, 11.7177°, 15.6252°, 17.1262°, 18.9052°, 19.4649°, 20.847°, 21.4135°, 21.9599°, 22.8698°, 23.4901°, 24.5954°, 26.0691°, 28.51°, and 31.4763°;

[0155] Preferably, the X-ray powder diffraction spectrum of Form XVII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9382°, 9.4506°, 9.7497°, 11.7177°, 15.0611°, 15.6252°, 17.1262°, 18.9052°, 19.4649°, 20.3109°, 20.847°, 21.4135°, 21.9599°, 22.8698°, 23.4901°, 24.5954°, 26.0691°, 26.689°, 28.51°, and 31.4763°;

[0156] Preferably, the X-ray powder diffraction spectrum of Form XVII represented by a diffraction angle of 2θ±0.2° is 3.9382°, 9.4506°, 9.7497°, 11.7177°, 13.0266°, 15.0611°, 15.6252°, 17.1262°, 18.9052°, 19.4649°, 20.3109°, 20.847 There are diffraction peaks at 21.4135°, 21.9599°, 22.8698°, 23.4901°, 24.5954°, 26.0691°, 26.689°, 28.51°, 30.6955°, 31.4763°, 32.5073°, 35.5318°, 36.311°, 37.2464°, and 39.6521°;

[0157] Preferably, Form XVII has one or more of the following characteristics:

[0158] (1) The TGA curve of Form XVII shows a weight loss of 15.13±1% at 200.0±3°C;

[0159] (2) The TGA curve of Form XVII has a decomposition endothermic peak at 316.6±3°C;

[0160] (3) The DSC curve of Form XVII has a desolvation endothermic peak at 146.9±3°C;

[0161] (4) The DSC curve of Form XVII has a melting endothermic peak at 223.4±3°C.

[0162] The X-ray powder diffraction spectrum of Form XVIII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0852°, 9.9044°, 18.2229°, 18.657°, 19.8834°, 25.403°, 27.4648°, 27.765°, and 28.6285°;

[0163] Preferably, the X-ray powder diffraction spectrum of Form XVIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0852°, 9.696°, 9.9044°, 15.5095°, 18.2229°, 18.657°, 19.8834°, 25.403°, 27.4648°, 27.765°, 28.6285°, and 37.173°;

[0164] Preferably, the X-ray powder diffraction spectrum of Form XVIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0852°, 9.696°, 9.9044°, 15.5095°, 18.2229°, 18.657°, 19.8834°, 22.9326°, 25.403°, 27.4648°, 27.765°, 28.6285°, 29.9839°, 37.173°, and 38.8939°;

[0165] Preferably, the X-ray powder diffraction spectrum of Form XVIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0852°, 9.696°, 9.9044°, 12.0086°, 15.5095°, 18.2229°, 18.657°, 19.8834°, 22.9326°, 25.403°, 26.3549°, 27.4648°, 27.765°, 28.6285°, 29.9839°, 37.173°, and 38.8939°;

[0166] Preferably, Form XVIII has one or more of the following characteristics:

[0167] (1) The TGA curve of Form XVIII shows a weight loss of 5.30±1% at 170.0±3°C;

[0168] (2) The TGA curve of Form XVIII has a decomposition endothermic peak at 284.8±3°C;

[0169] (3) The DSC curve of Form XVIII has a desolvation endothermic peak at 150.1±3°C;

[0170] (4) The DSC curve of Form XVIII has a melting endothermic peak at 224.6±3°C.

[0171] The X-ray powder diffraction spectrum of Form XIX expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.2306°, 9.7843°, 10.5597°, 15.2185°, 16.7197°, 18.6635°, 19.642°, 21.6489°, 24.2523°, and 25.9223°;

[0172] Preferably, the X-ray powder diffraction spectrum of Form XIX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2778°, 8.2306°, 9.1956°, 9.7843°, 10.5597°, 15.2185°, 16.7197°, 18.6635°, 19.642°, 21.6489°, 22.8118°, 24.2523°, 25.9223°, and 29.7113°;

[0173] Preferably, the X-ray powder diffraction spectrum of Form XIX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2778°, 8.2306°, 9.1956°, 9.7843°, 10.5597°, 15.2185°, 16.7197°, 18.6635°, 19.642°, 21.6489°, 22.8118°, 24.2523°, 25.9223°, 27.8768°, and 29.7113°;

[0174] Preferably, the X-ray powder diffraction spectrum of Form XIX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2778°, 8.2306°, 9.1956°, 9.7843°, 10.5597°, 12.8908°, 15.2185°, 16.7197°, 18.6635°, 19.642°, 21.6489°, 22.8118°, 24.2523°, 25.9223°, 27.8768°, and 29.7113°;

[0175] Preferably, Form XIX has one or more of the following characteristics:

[0176] (1) The TGA curve of Form XIX shows a weight loss of 5.30±1% at 150±3°C;

[0177] (2) The TGA curve of Form XIX has a decomposition endothermic peak at 275.5±3°C;

[0178] (3) The DSC curve of Form XIX has desolvation endothermic peaks at 105.2±3°C and 118.9±3°C;

[0179] (4) The DSC curve of Form XIX has a melting endothermic peak at 222.6±3°C.

[0180] The X-ray powder diffraction spectrum of Form XX expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.1562°, 16.3732°, 19.4177°, 19.9051°, 21.765°, 24.0195°, 24.6421°, and 27.6839°;

[0181] Preferably, the X-ray powder diffraction spectrum of Form XX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.9295°, 8.1562°, 9.8697°, 15.8946°, 16.3732°, 19.4177°, 19.9051°, 21.1077°, 21.765°, 24.0195°, 24.6421°, 25.8571°, 27.6839°, and 28.4482°;

[0182] Preferably, the X-ray powder diffraction spectrum of Form XX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.9295°, 6.2823°, 8.1562°, 9.8697°, 11.9239°, 13.7136°, 15.8946°, 16.3732°, 19.4177°, 19.9051°, 21.1077°, 21.765°, 24.0195°, 24.6421°, 25.8571°, 27.6839°, and 28.4482°;

[0183] Preferably, the X-ray powder diffraction spectrum of Form XX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.9295°, 6.2823°, 8.1562°, 9.8697°, 11.9239°, 13.7136°, 15.8946°, 16.3732°, 19.4177°, 19.9051°, 21.1077°, 21.765°, 24.0195°, 24.6421°, 25.8571°, 27.6839°, 28.4482°, 32.1403°, and 33.0643°;

[0184] Preferably, the crystalline form XX has one or more of the following characteristics:

[0185] (1) The TGA curve of Form XX shows a weight loss of 21.50±1% at 150±3°C;

[0186] (2) The TGA curve of Form XX has a decomposition endothermic peak at 307.5±3°C;

[0187] (3) The DSC curve of Form XX has a desolvation endothermic peak at 96.4±3°C;

[0188] (4) The DSC curve of Form XX has a melting endothermic peak at 223.5±3°C.

[0189] The X-ray powder diffraction spectrum of Form XXI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1247°, 9.4385°, 15.2708°, 16.1429°, 17.3222°, 17.6586°, 18.3906°, 18.734°, 19.217°, 20.0426°, 20.8807°, 21.3881°, 23.1609°, 23.5369°, 24.106°, 24.5057°, 26.0111°, and 26.2379°;

[0190] Preferably, the X-ray powder diffraction spectrum of Form XXI expressed at a diffraction angle of 2θ±0.2° is 8.2582°, 9.1247°, 9.4385°, 11.8388°, 13.0734°, 15.2708°, 15.6112°, 16.1429°, 17.3222°, 17.6586°, 18.1167°, 18.3906°, 18.734°, 19.2 There are diffraction peaks at 17°, 20.0426°, 20.8807°, 21.3881°, 22.0439°, 22.4864°, 23.1609°, 23.5369°, 23.8132°, 24.106°, 24.5057°, 24.8877°, 26.0111°, 26.2379°, 26.6445°, 27.8858°, and 28.7599°;

[0191] Preferably, the X-ray powder diffraction spectrum of Form XXI represented by a diffraction angle of 2θ±0.2° is 8.2582°, 9.1247°, 9.4385°, 10.3908°, 11.8388°, 13.0734°, 14.5829°, 15.2708°, 15.6112°, 16.1429°, 17.3222°, 17.6586°, 18.1167°, 18.3906°, 18.734°, 19.217°, 20.0426°, There are diffraction peaks at 20.8807°, 21.3881°, 22.0439°, 22.4864°, 23.1609°, 23.5369°, 23.8132°, 24.106°, 24.5057°, 24.8877°, 26.0111°, 26.2379°, 26.6445°, 27.1343°, 27.8858°, 28.7599°, 29.3559°, 30.0389°, 30.801°, and 31.824°;

[0192] Preferably, the X-ray powder diffraction spectrum of Form XXI represented by a diffraction angle of 2θ±0.2° is 8.2582°, 9.1247°, 9.4385°, 10.3908°, 10.8322°, 11.8388°, 13.0734°, 14.5829°, 15.2708°, 15.6112°, 16.1429°, 17.3222°, 17.6586°, 18.1167°, 18.3906°, 18.734°, 19.217°, 20.0426°, There are diffraction peaks at 20.8807°, 21.3881°, 22.0439°, 22.4864°, 23.1609°, 23.5369°, 23.8132°, 24.106°, 24.5057°, 24.8877°, 26.0111°, 26.2379°, 26.6445°, 27.1343°, 27.8858°, 28.7599°, 29.3559°, 30.0389°, 30.801°, 31.824°, and 32.6367°.

[0193] The X-ray powder diffraction spectrum of Form XXII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.303°, 8.8753°, 9.3235°, 10.4306°, 15.5408°, 16.9429°, 17.56°, 17.773°, 18.6982°, 19.0572°, 20.9194°, 21.1192°, 21.383°, 23.8992°, 24.1642°, 26.0356°, and 26.6018°;

[0194] Preferably, the X-ray powder diffraction spectrum of Form XXII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.303°, 8.8753°, 9.3235°, 10.4306°, 13.6912°, 15.5408°, 16.9429°, 17.56°, 17.773°, 18.6982°, 19.0572°, 19.4617°, 20.9194°, 21.1192°, 21.383°, 21.9111°, 22.4002°, 23.8992°, 24.1642°, 24.5292°, 26.0356°, 26.6018°, and 27.4938°;

[0195] Preferably, the X-ray powder diffraction spectrum of Form XXII represented by a diffraction angle of 2θ±0.2° is 8.303°, 8.8753°, 9.3235°, 10.4306°, 11.3337°, 12.9434°, 13.6912°, 15.5408°, 16.9429°, 17.56°, 17.773°, 18.6982°, 19.0572°, 1 There are diffraction peaks at 9.4617°, 20.9194°, 21.1192°, 21.383°, 21.9111°, 22.4002°, 23.0249°, 23.8992°, 24.1642°, 24.5292°, 26.0356°, 26.6018°, 27.4938°, 28.1751°, 28.5674°, and 29.7642°;

[0196] Preferably, the X-ray powder diffraction spectrum of Form XXII represented by a diffraction angle of 2θ±0.2° is 8.303°, 8.8753°, 9.3235°, 10.4306°, 11.3337°, 12.2858°, 12.9434°, 13.6912°, 14.6208°, 15.5408°, 15.8979°, 16.279°, 16.9429°, 17.56°, 17.773°, 18.698 There are diffraction peaks at 2°, 19.0572°, 19.4617°, 20.9194°, 21.1192°, 21.383°, 21.9111°, 22.4002°, 23.0249°, 23.8992°, 24.1642°, 24.5292°, 26.0356°, 26.6018°, 27.4938°, 28.1751°, 28.5674°, 29.7642°, and 31.2811°.

[0197] The X-ray powder diffraction spectrum of Form XXIII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7799°, 10.8113°, 11.1486°, 15.6173°, 16.2004°, 18.8244°, 20.2031°, 20.6918°, and 25.325°;

[0198] Preferably, the X-ray powder diffraction spectrum of Form XXIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7799°, 10.8113°, 11.1486°, 12.8168°, 15.6173°, 16.2004°, 18.8244°, 19.2693°, 20.2031°, 20.6918°, and 25.325°;

[0199] Preferably, the X-ray powder diffraction spectrum of Form XXIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7799°, 10.8113°, 11.1486°, 12.8168°, 14.2512°, 15.6173°, 16.2004°, 17.7301°, 18.8244°, 19.2693°, 20.2031°, 20.6918°, and 25.325°;

[0200] Preferably, the X-ray powder diffraction spectrum of Form XXIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7799°, 10.8113°, 11.1486°, 12.8168°, 14.2512°, 15.6173°, 16.2004°, 17.7301°, 18.8244°, 19.2693°, 20.2031°, 20.6918°, 22.0426°, and 25.325°;

[0201] Preferably, Form XXIII has one or more of the following characteristics:

[0202] (1) The TGA curve of Form XXIII shows a weight loss of 2.28±1% at 150±3°C;

[0203] (2) The TGA curve of Form XXIII has a decomposition endothermic peak at 264.8±3°C;

[0204] (3) The DSC curve of Form XXIII has a melting endothermic peak at 221.6±3°C.

[0205] The method for preparing the polymorph of the sGC agonist of the present invention is to adopt one of the following methods:

[0206] Method 1: Add compound I to a solvent, suspend and stir at 0-50°C for 4-7 days, centrifuge, remove the supernatant, and vacuum dry to obtain the compound I;

[0207] Method 2: Add compound I to a solvent and shake for 1-2 days, centrifuge, remove the supernatant, and vacuum dry to obtain;

[0208] Method 3: Add compound I to a good solvent and stir to dissolve, add the resulting solution to an anti-solvent and stir, filter, wash the resulting filter cake, and dry to obtain;

[0209] Method 4: Add compound I to a good solvent to dissolve, filter, add anti-solvent to the filtrate, stir, centrifuge, remove the supernatant, and vacuum dry to obtain;

[0210] Method 5: Add compound I to a solvent to dissolve, filter, place the filtrate in an anti-solvent environment for gas-liquid diffusion, centrifuge, remove the supernatant, and vacuum dry to obtain;

[0211] Method 6: Place compound I in a solvent environment for gas-solid diffusion to obtain;

[0212] Method 7: Compound I is added to a solvent, suspended and stirred at 0-50° C. for 4-7 days, centrifuged, the supernatant is removed, vacuum dried, and heat treated under nitrogen protection to obtain the product.

[0213] The solvent is one or both of water and an organic solvent. The organic solvent is one or more of alcohol, chloroalkane, ketone, ether, cyclic ether, ester, alkane, benzene, sulfoxide or amide. The organic solvent is preferably one or more of methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, butanone, ethyl acetate, isopropyl acetate, methyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, methyl tert-butyl ether, toluene, N-methylpyrrolidone, n-heptane, cyclohexane, 1,4-dioxane, dichloromethane or N,N-dimethylformamide.

[0214] The good solvent is one or more of dimethyl sulfoxide, methanol, ethanol, tetrahydrofuran or N,N-dimethylformamide, and the anti-solvent is one or more of isopropanol, acetone, ethyl acetate, isopropyl acetate, methyl acetate, acetonitrile, methyl tert-butyl ether, toluene, dichloromethane, water or n-hexane.

[0215] The use of the polymorphic form of the sGC agonist of the present invention, the pharmaceutical composition comprises at least one of form I, form II, form III, form IV, form V, form VI, form VII, form VIII, form IX, form X, form XI, form XII, form XIII, form XIV, form XV, form XVI, form XVII, form XVIII, form XIX, form XX, form XXI, form XXII or form XXIII and a pharmaceutically acceptable carrier.

[0216] The polymorphic form of the sGC agonist of the present invention is used for preparing medicines for treating lung diseases.

[0217] Pulmonary disease is pulmonary hypertension or pulmonary fibrosis.

[0218] The beneficial effects of the present invention are as follows:

[0219] The present invention provides a polymorph of the sGC agonist LXH-1211, which provides technical support for the subsequent research and development of drugs and maintaining the consistency of the pharmacokinetic and pharmacokinetic properties of the drugs, and can also provide technical support for the subsequent industrial production of drugs with specific crystal forms. BRIEF DESCRIPTION OF THE DRAWINGS

[0220] Figure 1 This is the XRPD spectrum of Form I.

[0221] Figure 2 This is the TGA / DSC spectrum of Form I.

[0222] Figure 3 This is the XRPD spectrum of Form II.

[0223] Figure 4 This is the TGA / DSC spectrum of Form II.

[0224] Figure 5 It is the XRPD spectrum of Form III.

[0225] Figure 6 It is the TGA / DSC spectrum of Form III.

[0226] Figure 7 This is the XRPD spectrum of Form IV.

[0227] Figure 8 This is the TGA / DSC spectrum of Form IV.

[0228] Fig. 9 This is the XRPD spectrum of Form V.

[0229] Fig.10 This is the TGA / DSC spectrum of Form V.

[0230] Fig.11 This is the XRPD spectrum of Form VI.

[0231] Fig.12 This is the TGA / DSC spectrum of Form VI.

[0232] Fig.13 This is the XRPD spectrum of Form VII.

[0233] Fig.14 It is the TGA / DSC spectrum of Form VII.

[0234] Fig.15 This is the XRPD spectrum of Form VIII.

[0235] Fig.16 This is the TGA / DSC spectrum of Form VIII.

[0236] Fig.17 This is the XRPD spectrum of Form IX.

[0237] Fig.18 This is the TGA / DSC spectrum of Form IX.

[0238] Fig.19This is the XRPD spectrum of Form X.

[0239] Fig. 20 This is the TGA / DSC spectrum of Form X.

[0240] Fig.21 This is the XRPD spectrum of Form XI.

[0241] Fig. 22 This is the TGA / DSC spectrum of Form XI.

[0242] Fig.23 This is the XRPD spectrum of Form XII.

[0243] Fig.24 This is the TGA / DSC spectrum of Form XII.

[0244] Fig.25 This is the XRPD spectrum of Form XIII.

[0245] Fig.26 This is the TGA / DSC spectrum of Form XIII.

[0246] Fig. 27 This is the XRPD spectrum of Form XIV.

[0247] Fig.28 This is the TGA / DSC spectrum of Form XIV.

[0248] Fig.29 This is the XRPD spectrum of Form XV.

[0249] Fig.30 This is the TGA / DSC spectrum of Form XV.

[0250] Fig.31 This is the XRPD spectrum of Form XVI.

[0251] Fig.32 This is the TGA / DSC spectrum of Form XVI.

[0252] Fig.33 This is the XRPD spectrum of Form XVII.

[0253] Fig.34 This is the TGA / DSC spectrum of Form XVII.

[0254] Fig.35 This is the XRPD spectrum of Form XVIII.

[0255] Fig.36 This is the TGA / DSC spectrum of Form XVIII.

[0256] Fig.37 This is the XRPD spectrum of Form XIX.

[0257] Fig.38 This is the TGA / DSC spectrum of Form XIX.

[0258] Fig.39 This is the XRPD spectrum of Form XX.

[0259] Fig.40 This is the TGA / DSC spectrum of Form XX.

[0260] Fig.41 This is the XRPD spectrum of Form XXI.

[0261] Fig.42 This is the XRPD spectrum of Form XXII.

[0262] Fig.43 This is the XRPD spectrum of Form XXIII.

[0263] Fig.44 This is the TGA / DSC spectrum of Form XXIII.

[0264] Fig.45 It is the XRPD spectrum of the solid-state stability experiment. In the figure, 0D: XRPD spectrum of the sample before test, 60-5D: XRPD spectrum of the sample after being placed at 60℃ for 5 days, 90%RH-5D: XRPD spectrum of the sample after being placed at 25℃ / 90%RH for 5 days, GZ-5D: XRPD spectrum of the sample after being placed under light conditions for 5 days, 60-10D: XRPD spectrum of the sample after being placed at 60℃ for 10 days, 90%RH-10D: XRPD spectrum of the sample after being placed at 25℃ / 90%RH for 10 days, GZ-10D: XRPD spectrum of the sample after being placed under light conditions for 10 days.

[0265] Fig.46 This is the XRPD spectrum of the mechanical stability experiment.

[0266] Fig.47 This is the XRPD spectrum of the pressure stability experiment. DETAILED DESCRIPTION

[0267] The present invention is further described below with reference to the embodiments.

[0268] Definition and Description

[0269] Unless otherwise specified, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those of ordinary skill in the art to which the present invention belongs. All patents and publications to which the present invention relates are incorporated herein by reference in their entirety. Although any methods and materials similar or identical to those described herein may be used in the practice or testing of the present invention, preferred methods, apparatus and materials are described herein.

[0270] "Crystal form" or "crystalline form" refers to a solid having a highly regular chemical structure, including, but not limited to, single-component or multi-component crystals, and / or polymorphs, solvates, hydrates, inclusion compounds, co-crystals, salts, solvates of salts, hydrates of salts of compounds. The crystalline form of a substance can be obtained by many methods known in the art. Such methods include, but are not limited to, melt crystallization, melt cooling, solvent crystallization, crystallization in a confined space, for example, in a nanopore or capillary, crystallization on a surface or template, for example, on a polymer, crystallization in the presence of an additive such as a co-crystallization countermolecule, desolvation, dehydration, rapid evaporation, rapid cooling, slow cooling, vapor diffusion, sublimation, reactive crystallization, anti-solvent addition, grinding and solvent drop grinding, etc.

[0271] "Solvent" refers to a substance (typically a liquid) that can completely or partially dissolve another substance (typically a solid). Solvents used in embodiments of the present invention include, but are not limited to, water, methanol, ethanol, isopropanol, dimethyl sulfoxide, acetone, butanone, ethyl acetate, isopropyl acetate, methyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, methyl tert-butyl ether, toluene, N-methylpyrrolidone, n-heptane, cyclohexane, 1,4-dioxane, dichloromethane, N,N-dimethylformamide, and the like.

[0272] "Anti-solvent" refers to a fluid that promotes precipitation of a product (or a product precursor) from a solvent. The anti-solvent may include a cold gas, or a fluid that promotes precipitation by a chemical reaction, or a fluid that reduces the solubility of the product in the solvent; it may be the same liquid as the solvent but at a different temperature, or it may be a different liquid from the solvent.

[0273] X-ray powder diffraction (XRPD) can detect information such as changes in crystal forms, crystallinity, and crystal structure states, and is a common means of identifying crystal forms. The peak position of the XRPD spectrum depends mainly on the structure of the crystal form, is relatively insensitive to experimental details, and its relative peak height depends on many factors related to sample preparation and instrument geometry. Therefore, in some embodiments, the crystal form of the present invention is characterized by an XRPD pattern with certain peak positions, which is substantially as shown in the XRPD pattern provided in the accompanying drawings of the present invention. At the same time, the measurement of 2θ of the XRPD spectrum may have experimental errors, and the measurement of 2θ of the XRPD spectrum may be slightly different between different instruments and different samples, so the value of 2θ cannot be regarded as absolute. According to the instrument conditions used in the test of the present invention, there is an error tolerance of ±0.2° for the diffraction peak.

[0274] Differential scanning calorimetry (DSC) is a technique that measures the energy difference between a sample and an inert reference material (commonly used α-Al2O3) as it changes with temperature by continuously heating or cooling under program control. The melting peak height of the DSC curve depends on many factors related to sample preparation and instrument geometry, while the peak position is relatively insensitive to experimental details. Therefore, in some embodiments, the crystal form described in the present invention is characterized by a DSC curve with a characteristic peak position, which is substantially as shown in the DSC curve provided in the accompanying drawings of the present invention. At the same time, the DSC curve may have experimental errors, and the peak position and peak value of the DSC curve may be slightly different between different instruments and different samples, so the peak position or peak value of the DSC endothermic peak cannot be regarded as absolute. According to the instrument conditions used in the test of the present invention, there is an error tolerance of ±3°C for the melting peak.

[0275] Solids with the same chemical composition often form isomers with different crystal structures, or variants, under different thermodynamic conditions. This phenomenon is called polymorphism or polyphase phenomenon. When the temperature and pressure conditions change, the variants will transform into each other, which is called crystal transformation. Due to the crystal transformation, the mechanical, electrical, magnetic and other properties of the crystal will change greatly. When the temperature of the crystal transformation is within the measurable range, this transformation process can be observed on the differential scanning calorimetry (DSC) curve, which is characterized in that the DSC curve has an exothermic peak reflecting this transformation process, and at the same time has two or more endothermic peaks, which are the characteristic endothermic peaks of different crystal forms before and after the transformation. The crystal form of the compound of the present invention can undergo crystal transformation under appropriate conditions.

[0276] Thermogravimetric analysis (TGA) is a technique for measuring the mass change of a substance with temperature under program control. It is suitable for checking the loss of solvent in crystals or the process of sample sublimation and decomposition, and can infer the presence of crystal water or crystallization solvent in the crystals. The mass change shown by the TGA curve depends on many factors such as sample preparation and instrumentation; the mass change detected by TGA varies slightly between different instruments and different samples. According to the instrument conditions used in the test of the present invention, the mass change has an error tolerance of ±0.3%.

[0277] In the context of the present invention, the 2θ (°2Th., °2Theta or Two Theta) values ​​in the X-ray powder diffraction pattern are all in degrees (°).

[0278] In the present invention, "room temperature" generally refers to 22°C to 28°C unless otherwise specified.

[0279] When referring to a spectrum and / or data appearing in a graph, a "peak" refers to a feature that can be identified by one skilled in the art and which cannot be attributed to background noise.

[0280] In the context of the present invention, when or whether the words "about" or "approximately" are used, it means within 10%, suitably within 5%, and especially within 1% of a given value or range. Alternatively, for those of ordinary skill in the art, the term "about" or "approximately" means within an acceptable standard error range of the mean. Whenever a number having a value of N is disclosed, any number having a value within N+ / -1%, N+ / -2%, N+ / -3%, N+ / -5%, N+ / -7%, N+ / -8% or N+ / -10% will be explicitly disclosed, where "+ / -" means plus or minus.

[0281] The term "comprising" is an open expression, that is, including the contents specified in the present invention but not excluding other contents.

[0282] The test method is as follows:

[0283] 1. X-ray powder diffraction (XRPD)

[0284] XRPD test conditions: detection instrument: Rigaku SmartLab SE; detection conditions: X-ray tube voltage 40 kV, X-ray tube current 40 mA, scanning range 3-40° (2θ), step size 0.02°, scanning speed 5° / min.

[0285] 2. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC)

[0286] TGA / DSC test conditions: detection instrument: NETZSCH STA 449F3; detection conditions: nitrogen, 50 mL / min; scanning program: 30-400°C, heating rate: 10°C / min; detection sample amount: 3 mg (alumina sample pan).

[0287] Example 1

[0288] Take 1.0g of compound I, add it to 20mL of N,N-dimethylformamide, heat it to 80℃, stir and dissolve it, keep it warm and stir for 1 hour; slowly add the resulting solution dropwise to purified water, stir overnight; filter, wash the filter cake with purified water, and then vacuum dry it at 50℃, take a sample for testing, and mark it as crystal form I. The test results are shown in Figure 1 and Figure 2 . Figure 2 The DSC results show that the sample has a desolvation endothermic peak near 132.1°C and a melting endothermic peak near 222.9°C. Figure 2 The TGA results showed that the sample lost 9.65% weight when heated from room temperature to 180°C; the sample began to decompose at around 291.5°C.

[0289] The XRPD diffraction peak data of Form I are shown in Table 1.

[0290] Table 1 XRPD diffraction peak data of Form I

[0291]

[0292] Example 2

[0293] Take 50 mg of compound I, add it to 1 mL of methanol, suspend and stir at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry it at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form II. The test results are shown in Figure 3 and Figure 4 . Figure 4 The DSC results show that the sample has a desolvation endothermic peak near 201.9℃ and a melting endothermic peak near 225.1℃. Figure 4 The TGA results showed that the sample lost 1.06% weight when heated from room temperature to 150°C; the sample began to decompose around 284.0°C.

[0294] The XRPD diffraction peak data of Form II are shown in Table 2.

[0295] Table 2 XRPD diffraction peak data of Form II

[0296]

[0297] Example 3

[0298] Take 50 mg of compound I, suspend and stir in 1 ml of isopropanol at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form III. The test results are shown in Figure 5 and Figure 6 . Figure 6 The TGA results showed that the sample lost 12.87% weight when heated from room temperature to 160°C; at around 273.7°C, the sample began to decompose. Figure 6 The DSC results show that the sample has a desolvation endothermic peak near 135.6°C and a melting endothermic peak near 222.5°C.

[0299] The XRPD diffraction peak data of Form III are shown in Table 3.

[0300] Table 3 XRPD diffraction peak data of Form III

[0301]

[0302]

[0303] Example 4

[0304] Take 50 mg of compound I, suspend and stir in 1 ml of acetone at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form IV. The test results are shown in Figure 7 and Figure 8 . Figure 8 The TGA results showed that the sample lost 7.7% weight when heated from room temperature to 160°C; the sample began to decompose at around 281.1°C. Figure 8 The DSC results show that the sample has a desolvation endothermic peak near 114.8°C and a melting endothermic peak near 224.7°C.

[0305] The XRPD diffraction peak data of Form IV are shown in Table 4.

[0306] Table 4 XRPD diffraction peak data of Form IV

[0307]

[0308] Example 5

[0309] Take 50 mg of compound I, suspend and stir in 1 ml of butanone at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form V. The test results are shown in Fig. 9 and Fig.10 . Fig.10 The TGA results showed that the sample lost 9.41% weight when heated from room temperature to 150°C; the sample began to decompose around 275.4°C. Fig.10 The DSC results show that the sample has a desolvation endothermic peak near 114.4°C and a melting endothermic peak near 222.1°C.

[0310] The XRPD diffraction peak data of Form V are shown in Table 5.

[0311] Table 5 XRPD diffraction peak data of Form V

[0312]

[0313] Example 6

[0314] Take 50 mg of compound I, suspend and stir in 1 ml of ethyl acetate at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form VI. The test results are shown in Fig.11 and Fig.12 . Fig.12 The TGA results showed that the sample lost 9.82% weight when heated from room temperature to 150°C; the sample began to decompose around 279.0°C. Fig.12 The DSC results show that the sample has a desolvation endothermic peak near 129.6°C and a melting endothermic peak near 224.2°C.

[0315] The XRPD diffraction peak data of Form VI are shown in Table 6.

[0316] Table 6 XRPD diffraction peak data of Form VI

[0317]

[0318]

[0319] Example 7

[0320] Take 50 mg of compound I, suspend and stir in 1 ml of methyl acetate at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as Form VII. The test results are shown in Fig.13 and Fig.14 . Fig.14 The TGA results showed that the sample lost 6.77% weight when heated from room temperature to 150°C; the sample began to decompose at around 286.8°C. Fig.14 The DSC results show that the sample has a desolvation endothermic peak near 117.4°C and a melting endothermic peak near 223.3°C.

[0321] The XRPD diffraction peak data of Form VII are shown in Table 7.

[0322] Table 7 XRPD diffraction peak data of Form VII

[0323]

[0324] Example 8

[0325] Take 50 mg of compound I, suspend and stir in 1 ml of tetrahydrofuran at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form VIII. The test results are shown in Fig.15 and Fig.16 . Fig.16 The TGA results showed that the sample lost 12.97% weight when heated from room temperature to 150°C; the sample began to decompose at around 294.7°C. Fig.16 The DSC results show that the sample has a desolvation endothermic peak near 121.3°C and a melting endothermic peak near 226.0°C.

[0326] The XRPD diffraction peak data of Form VIII are shown in Table 8.

[0327] Table 8 XRPD diffraction peak data of Form VIII

[0328]

[0329]

[0330] Example 9

[0331] 50 mg of compound I was suspended in 1 ml of 2-methyltetrahydrofuran at room temperature for 4 days, centrifuged, the supernatant was removed, and vacuum dried at 40°C for 4 hours. Samples were taken for testing and marked as Form IX. The test results are shown in Fig.17 and Fig.18 . Fig.18 The TGA results showed that the sample lost 8.19% weight when heated from room temperature to 150°C; the sample began to decompose around 273.0°C. Fig.18 The DSC results show that the sample has a desolvation endothermic peak near 114.3°C and a melting endothermic peak near 222.6°C.

[0332] The XRPD diffraction peak data of Form IX are shown in Table 9.

[0333] Table 9 XRPD diffraction peak data of Form IX

[0334]

[0335]

[0336] Example 10

[0337] Take 50 mg of compound I, suspend and stir in 1 ml of acetonitrile at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form X. The test results are shown in Fig.19 and Fig. 20 . Fig. 20 The TGA results showed that the sample lost 4.77% weight when heated from room temperature to 150°C; the sample began to decompose around 281.5°C. Fig. 20 The DSC results show that the sample has a desolvation endothermic peak near 119.6°C and a melting endothermic peak near 224.3°C.

[0338] The XRPD diffraction peak data of Form X are shown in Table 10.

[0339] Table 10 XRPD diffraction peak data of Form X

[0340]

[0341] Embodiment 11

[0342] 50 mg of compound I was suspended in 1 ml of methyl tert-butyl ether at room temperature for 4 days, centrifuged, the supernatant was removed, and vacuum dried at 40°C for 4 hours. Samples were taken for testing and marked as crystal form XI. The test results are shown in Fig.21 and Fig. 22 . Fig. 22 The TGA results showed that the sample lost 6.73% weight when heated from room temperature to 150°C; the sample began to decompose around 276.4°C. Fig. 22 The DSC results show that the sample has a desolvation endothermic peak near 103.3°C and a melting endothermic peak near 222.6°C.

[0343] The XRPD diffraction peak data of Form XI are shown in Table 11.

[0344] Table 11 XRPD diffraction peak data of Form XI

[0345]

[0346] Example 12

[0347] Take 50 mg of compound I, suspend and stir in 1 ml of toluene at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form XII. The test results are shown in Fig.23 and Fig.24 . Fig.24 The TGA results showed that the sample lost 7.91% weight when heated from room temperature to 120°C, and lost 7.31% weight when heated continuously to 200°C; the sample began to decompose at around 275.4°C. Fig.24The DSC results show that the sample has desolvation endothermic peaks near 97.5℃ and 145.7℃, and a melting endothermic peak near 222.9℃.

[0348] The XRPD diffraction peak data of Form XII are shown in Table 12.

[0349] Table 12 XRPD diffraction peak data of Form XII

[0350]

[0351]

[0352] Example 13

[0353] Take 50 mg of compound I, suspend and stir in 1 ml of water at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form XIII. Fig.25 and Fig.26 . Fig.26 The TGA results showed that the sample lost 2.74% weight when heated from room temperature to 150°C; the sample began to decompose around 251.1°C. Fig.26 The DSC results show that the sample has desolvation endothermic peaks near 69.9℃ and 101.5℃, and a melting endothermic peak near 221.9℃.

[0354] The XRPD diffraction peak data of Form XIII are shown in Table 13.

[0355] Table 13 XRPD diffraction peak data of Form XIII

[0356]

[0357] Embodiment 14

[0358] 50 mg of compound I was suspended in 1 ml of N-methylpyrrolidone at room temperature for 4 days, centrifuged, the supernatant was removed, and vacuum dried at 40°C for 4 hours. Samples were taken for testing and marked as Form XIV. The test results are shown in Fig. 27 and Fig.28 . Fig.28 The TGA results showed that the sample lost 18.92% weight when heated from room temperature to 200°C; the sample began to decompose around 287.3°C. Fig.28 The DSC results show that the sample has a desolvation endothermic peak near 144.2°C and a melting endothermic peak near 222.5°C.

[0359] The XRPD diffraction peak data of Form XIV are shown in Table 14.

[0360] Table 14 XRPD diffraction peak data of Form XIV

[0361]

[0362]

[0363] Embodiment 15

[0364] Take 50 mg of compound I, suspend and stir in 1 ml of 1,4-dioxane at room temperature for 4 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form XV. Fig.29 and Fig.30 . Fig.30 The TGA results show that the sample loses 10.41% weight when heated from room temperature to 200°C; the sample begins to decompose around 270.0°C. Fig.30 The DSC results show that the sample has a desolvation endothermic peak near 150.9°C and a melting endothermic peak near 222.6°C.

[0365] The XRPD diffraction peak data of Form XV are shown in Table 15.

[0366] Table 15 XRPD diffraction peak data of Form XV

[0367]

[0368]

[0369] Example 16

[0370] Take 50 mg of compound I, suspend and stir in 1 ml of dichloromethane at 40°C for 4 days, cool to room temperature, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, take a sample for testing, and mark it as crystal form XVI. The test results are shown in Fig.31 and Fig.32 . Fig.32 The TGA results showed that the sample lost 8.51% weight when heated from room temperature to 150°C; the sample began to decompose around 276.9°C. Fig.32 The DSC results show that the sample has a desolvation endothermic peak near 115.7°C and a melting endothermic peak near 222.7°C.

[0371] The XRPD diffraction peak data of Form XVI are shown in Table 16.

[0372] Table 16 XRPD diffraction peak data of Form XVI

[0373]

[0374]

[0375] Embodiment 17

[0376] Take 50 mg of compound I, add 1 mL of dimethyl sulfoxide to dissolve it, filter it, put the filtrate in a sample bottle, and then put the sample bottle containing the filtrate in an isopropanol environment for gas-liquid diffusion for 7 days. Centrifuge the sample bottle, remove the supernatant, vacuum dry it at 40°C for 4 hours, and then take a sample for testing, which is marked as crystal form XVII. The test results are shown in Fig.33 and Fig.34 . Fig.34 The TGA results show that the sample loses 15.13% weight when heated from room temperature to 200°C; the sample begins to decompose around 316.6°C. Fig.34 The DSC results show that the sample has a desolvation endothermic peak near 146.9°C and a melting endothermic peak near 223.4°C.

[0377] The XRPD diffraction peak data of Form XVII are shown in Table 17.

[0378] Table 17 XRPD diffraction peak data of Form XVII

[0379]

[0380] Embodiment 18

[0381] Take 30 mg of compound I, place compound I in an acetone environment for 7 days, obtain solid by gas-solid diffusion, take the solid for testing, and mark it as crystal form XVIII. The test results are shown in Fig.35 and Fig.36 . Fig.36 The TGA results showed that the sample lost 5.30% weight when heated from room temperature to 170°C, and the sample began to decompose around 284.8°C. Fig.36 The DSC results show that the sample has a desolvation endothermic peak near 150.1℃ and a melting endothermic peak near 224.6℃.

[0382] The XRPD diffraction peak data of Form XVIII are shown in Table 18.

[0383] Table 18 XRPD diffraction peak data of Form XVIII

[0384]

[0385] Embodiment 19

[0386] 30 mg of compound I was placed in a dichloromethane environment for 7 days, and a solid was obtained by gas-solid diffusion. The solid was tested and marked as crystal form XIX. The test results are shown in Fig.37 and Fig.38 . Fig.38 The TGA results showed that the sample lost 3.99% weight when heated from room temperature to 150°C; the sample began to decompose around 275.5°C. Fig.38 The DSC results show that the sample has desolvation endothermic peaks near 105.2℃ and 118.9℃, and a melting endothermic peak near 222.6℃.

[0387] The XRPD diffraction peak data of Form XIX are shown in Table 19.

[0388] Table 19 XRPD diffraction peak data of Form XIX

[0389]

[0390] Embodiment 20

[0391] Take 50 mg of compound I, add tetrahydrofuran to dissolve it, filter it, put the filtrate in a sample bottle, slowly add 9 times the volume of toluene to the sample bottle, stir for 18 hours after solid precipitation, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, take a sample for testing, and mark it as crystal form XX. Test results are shown in Fig.39 and Fig.40 . Fig.40 The TGA results show that the sample loses 21.50% weight when heated from room temperature to 150°C; the sample begins to decompose around 307.5°C. Fig.40 The DSC results show that the sample has a desolvation endothermic peak near 96.4°C and a melting endothermic peak near 223.5°C.

[0392] The XRPD diffraction peak data of Form XX are shown in Table 20.

[0393] Table 20 XRPD diffraction peak data of Form XX

[0394]

[0395] Embodiment 21

[0396] Take 50 mg of compound I, suspend and stir in 1 ml of ethanol at room temperature for 7 days, centrifuge, remove the supernatant, vacuum dry at 40°C for 4 hours, take a sample for testing, and mark it as crystal form XXI. The test results are shown in Fig.41 The XRPD diffraction peak data of Form XXI are shown in Table 21.

[0397] Table 21 XRPD diffraction peak data of Form XXI

[0398]

[0399]

[0400] Embodiment 22

[0401] Take 50 mg of compound I, suspend and stir in 1 ml of acetonitrile at room temperature for 4 days, centrifuge, remove the supernatant, dry in vacuum at 40°C for 4 hours, heat to 150°C under nitrogen protection, take a sample for testing, and mark it as crystal form XXII. The test results are shown in Fig.42 .

[0402] The XRPD diffraction peak data of Form XXII are shown in Table 22.

[0403] Table 22 XRPD diffraction peak data of Form XXII

[0404]

[0405] Embodiment 23

[0406] Take 50 mg of compound I, shake it in water at 200 rpm for 24 hours, centrifuge it, remove the supernatant, dry it in vacuum at 40°C for 4 hours, take a sample for testing, and mark it as crystal form XXIII. Fig.43 and Fig.44 . Fig.44 The TGA results showed that the sample lost 2.28% weight when heated from room temperature to 150°C; the sample began to decompose around 264.8°C. Fig.44 The DSC results showed that the sample had a melting endothermic peak near 221.6°C.

[0407] The XRPD diffraction peak data of Form XXIII are shown in Table 23.

[0408] Table 23 XRPD diffraction peak data of Form XXIII

[0409]

[0410] The crystal form experiment is as follows:

[0411] 1. Suspension competition experiment

[0412] (1) A suspension competition experiment was conducted on Forms XI and II at different temperatures to determine their stability. The specific operation and results are as follows: Equal amounts of Forms XI and II were suspended and competitively slurried in an n-heptane system. The results are shown in Table 24. The experimental results show that Forms XI and II were slurried at 10°C, room temperature and 50°C for 3 days, and the samples were converted into Form XI. Therefore, within the range of 10°C to 50°C, Form XI is thermodynamically more stable than Form II.

[0413] Table 24 Suspension competition test results between Form XI and Form II

[0414]

[0415] (2) Crystal forms XXII, XXIII and XI were suspended and slurried to investigate their relative stability. The results are shown in Table 25. The experimental results show that when crystal forms XXII, XXIII and XI were suspended and slurried in a n-heptane solvent system at room temperature for 3 days, all samples were converted into crystal form XI. Therefore, crystal form XI is more stable than crystal forms XXII and XXIII at room temperature.

[0416] Table 25 Suspension competition test results between Form XXII, Form XXIII and Form XI

[0417]

[0418] (3) Forms I, III, X, XIII, XVI, XIX and XI were suspended and slurried in a mixed solvent of water / methyl tert-butyl ether at different volume percentages at room temperature for 7 days. The results are shown in Table 26. The experimental results show that in V 水 When the content of % is less than 10%, all the tested crystalline forms are transformed into crystalline form XI, and crystalline form XI remains crystalline stable.

[0419] Table 26 Suspension test results of different crystal forms in water / methyl tert-butyl ether mixed solvents with different volume percentages

[0420]

[0421] 2. Solid-state stability test

[0422] 30 mg of Form XI was placed under three conditions: illumination (cold white light, 5000 Lux ± 500 Lux; closed), 60°C (closed), and 25°C / 90% RH (open) for 5 days and 10 days respectively. The solid samples after placement were subjected to XRPD testing to analyze the stability of the crystal form. The specific experimental results are shown in Table 27 and Fig.45 : The results showed that after being placed under light, high humidity and high temperature conditions for 5 days and 10 days, the crystal form of Form XI did not undergo obvious changes.

[0423] Table 27 XRPD results of solid state stability samples

[0424] Stability conditions XRPD (5 days) XRPD (10 days) illumination No change No change 25℃&90%RH No change No change 60℃ No change No change

[0425] 3. Mechanical stability test

[0426] 30 mg of Form XI was placed in a mortar and manually ground for 1 minute and 3 minutes, respectively, and then XRPD tests were performed. The results are shown in Table 28 and Fig.46 The experimental results show that the crystal state of Form XI remains basically unchanged after manual grinding for 1 minute and 3 minutes.

[0427] Table 28 XRPD results of mechanical stability samples

[0428] Stability conditions XRPD (1 minute) XRPD (3 minutes) Manual grinding Crystal form XI Crystal form XI

[0429] 4. Pressure stability test

[0430] 30 mg of Form XI was placed under a pressure of 4 MPa and XRPD tests were performed after 1 minute and 3 minutes. The results are shown in Table 29 and Fig.47 The experimental results show that the crystal state of Form XI remains basically unchanged after 1 minute and 3 minutes under a pressure of 4 MPa.

[0431] Table 29 XRPD results of pressure stable samples

[0432] Pressure stability conditions XRPD (1 minute) XRPD (3 minutes) 4Mpa Crystal form XI Crystal form XI

Claims

1. A polymorph of a sGC agonist, characterized in that The polymorph of the sGC agonist is a polymorph of Compound I, and the structural formula of Compound I is as follows: The polymorphic forms of Compound I include Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, Form X, Form XI, Form XII, Form XIII, Form XIV, Form XV, Form XVI, Form XVII, Form XVIII, Form XIX, Form XX, Form XXI, Form XXII and Form XXIII.

2. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form I expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0108°, 9.5975°, 11.8529°, 13.1094°, 18.1392°, 18.9765°, 19.6892°, 22.9121°, 24.5164°, and 27.2046°; Preferably, the X-ray powder diffraction spectrum of Form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0108°, 9.2291°, 9.5975°, 10.7891°, 11.8529°, 13.1094°, 16.2972°, 17.5452°, 18.1392°, 18.4776°, 18.9765°, 19.6892°, 20.1756°, 20.5641°, 22.7598°, 22.9121°, 23.8564°, 24.5164°, 27.2046°, and 27.7852°; Preferably, the X-ray powder diffraction spectrum of Form I represented by a diffraction angle of 2θ±0.2° is 9.0108°, 9.2291°, 9.5975°, 9.8422°, 10.5397°, 10.7891°, 11.8529°, 12.3461°, 13.1094°, 15.3009°, 15.5385°, 15.9365°, 16.2972°, 16.5676°, 16.7064°, 17.5452°, 18.1392°, 18.4776°, 1 There are diffraction peaks at 8.9765°, 19.6892°, 20.1756°, 20.5641°, 20.7731°, 21.072°, 21.6182°, 22.1326°, 22.7598°, 22.9121°, 23.8564°, 24.2325°, 24.5164°, 26.3531°, 26.9224°, 27.2046°, 27.4413°, 27.7852°, 28.2752°, 29.6917°, and 30.5549°; Preferably, the X-ray powder diffraction spectrum of Form I represented by a diffraction angle of 2θ±0.2° is 3.9655°, 6.573°, 8.4859°, 9.0108°, 9.2291°, 9.5975°, 9.8422°, 10.5397°, 10.7891°, 11.8529°, 12.3461°, 13.1094°, 14.0714°, 14.9594°, 15.3009°, 15.5385°, 15.9365°, 16.2972°, 16.5676°, 16.7064°, 17.5452°, 18.1392°, 18.4776°, 18.9765° There are diffraction peaks at 19.6892°, 20.1756°, 20.5641°, 20.7731°, 21.072°, 21.6182°, 22.1326°, 22.7598°, 22.9121°, 23.8564°, 24.2325°, 24.5164°, 25.0865°, 25.4534°, 26.3531°, 26.9224°, 27.2046°, 27.4413°, 27.7852°, 28.2752°, 28.9362°, 29.2808°, 29.6917°, 30.5549°, 31.3961°, and 32.1292°; Preferably, Form I has one or more of the following characteristics: (1) The TGA curve of Form I shows a weight loss of 9.65±1% at 180.0±3°C; (2) The TGA curve of Form I has a decomposition endothermic peak starting point at 291.5±3°C; (3) The DSC curve of Form I has a desolvation endothermic peak at 132.1±3°C; (4) The DSC curve of Form I has a melting endothermic peak at 222.9±3℃.

3. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form II expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.118°, 10.5628°, 16.2631°, 16.7055°, 18.2844°, 18.6888°, 23.2135°, 23.7283°, 24.7652°, and 24.9396°; Preferably, the X-ray powder diffraction spectrum of Form II represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.118°, 9.8184°, 10.5628°, 12.5988°, 13.6591°, 15.2348°, 15.4213°, 16.2631°, 16.7055°, 18.2844°, 18.6888°, 18.9162°, 19.6482°, 21.7878°, 22.0415°, 23.2135°, 23.7283°, 24.7652°, 24.9396°, 25.243°, and 25.8567°; Preferably, the X-ray powder diffraction spectrum of Form II represented by a diffraction angle of 2θ±0.2° is 7.934°, 9.118°, 9.2902°, 9.8184°, 10.5628°, 10.9728°, 12.5988°, 13.6591°, 15.2348°, 15.4213°, 16.2631°, 16.7055°, 18.0402°, 18.2844°, 18.6888°, 18.9162°, 19.124 There are diffraction peaks at 4°, 19.4049°, 19.6482°, 20.0337°, 20.3903°, 21.4219°, 21.7878°, 22.0415°, 22.3281°, 22.8857°, 23.2135°, 23.7283°, 24.7652°, 24.9396°, 25.243°, 25.8567°, 26.378°, 27.1598°, 27.5634°, and 31.3168°; Preferably, the X-ray powder diffraction spectrum of Form II represented by a diffraction angle of 2θ±0.2° is 7.934°, 9.118°, 9.2902°, 9.8184°, 10.5628°, 10.9728°, 12.5988°, 13.6591°, 15.2348°, 15.4213°, 16.2631°, 16.7055°, 18.0402°, 18.2844°, 18.6888°, 18.9162°, 19.1244°, 19.4049°, 19.648 There are diffraction peaks at 2°, 20.0337°, 20.3903°, 21.4219°, 21.7878°, 22.0415°, 22.3281°, 22.8857°, 23.2135°, 23.7283°, 24.7652°, 24.9396°, 25.243°, 25.8567°, 26.378°, 27.1598°, 27.5634°, 29.4736°, 31.3168°, 32.1421°, 32.9129°, and 38.1754°; Preferably, Form II has one or more of the following characteristics: (1) The TGA curve of Form II shows a weight loss of 1.06±1% at 150.0±3°C; (2) The TGA curve of Form II has a decomposition endothermic peak starting point at 284.0±3°C; (3) The DSC curve of Form II has a desolvation endothermic peak at 201.9±3°C; (4) The DSC curve of Form II has a melting endothermic peak at 225.1±3°C.

4. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form III expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9297°, 9.8289°, 16.6539°, 17.8685°, 18.1427°, 19.5768°, 21.5442°, 21.7443°, 24.7395°, and 25.6847°; Preferably, the X-ray powder diffraction spectrum of Form III represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9297°, 9.8289°, 14.9608°, 15.7384°, 16.6539°, 17.8685°, 18.1427°, 19.5768°, 21.5442°, 21.7443°, 22.6617°, 24.7395°, 25.6847°, and 26.9319°; Preferably, the X-ray powder diffraction spectrum of Form III represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9297°, 9.8289°, 14.6479°, 14.9608°, 15.7384°, 16.6539°, 17.8685°, 18.1427°, 19.5768°, 21.5442°, 21.7443°, 22.6617°, 24.7395°, 25.6847°, 26.9319°, 28.1208°, and 29.837°; Preferably, the X-ray powder diffraction spectrum of Form III represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9297°, 9.8289°, 11.9127°, 14.6479°, 14.9608°, 15.7384°, 16.6539°, 17.8685°, 18.1427°, 19.5768°, 21.5442°, 21.7443°, 22.6617°, 24.7395°, 25.6847°, 26.9319°, 28.1208°, 29.837°, 31.5086°, 33.166°, and 36.3974°; Preferably, Form III has one or more of the following characteristics: (1) The TGA curve of Form III shows a weight loss of 12.87±1% at 160.0±3°C; (2) The TGA curve of Form III has a decomposition endothermic peak starting point at 273.7±3°C; (3) The DSC curve of Form III has a desolvation endothermic peak at 135.6±3°C; (4) The DSC curve of Form III has a melting endothermic peak at 222.5±3°C.

5. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form IV expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.2951°, 17.9978°, 18.5726°, 19.7368°, 21.6855°, and 25.2649°; Preferably, the X-ray powder diffraction spectrum of Form IV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.2951°, 10.3942°, 16.6591°, 17.9978°, 18.5726°, 19.7368°, 20.8526°, 21.6855°, 23.8965°, 25.2649°, and 26.2148°; Preferably, the X-ray powder diffraction spectrum of Form IV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.2931°, 9.2951°, 10.3942°, 14.5845°, 16.6591°, 17.9978°, 18.5726°, 19.7368°, 20.8526°, 21.6855°, 23.8965°, 25.2649°, and 26.2148°; Preferably, the X-ray powder diffraction spectrum of Form IV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.2931°, 9.2951°, 10.3942°, 14.5845°, 16.6591°, 17.9978°, 18.5726°, 19.7368°, 20.8526°, 21.6855°, 23.8965°, 25.2649°, 26.2148°, and 29.7988°; Preferably, Form IV has one or more of the following characteristics: (1) The TGA curve of Form IV shows a weight loss of 7.70±1% at 160.0±3°C; (2) The TGA curve of Form IV has a decomposition endothermic peak starting point at 281.1±3°C; (3) The DSC curve of Form IV has a desolvation endothermic peak at 114.8±3°C; (4) The DSC curve of Form IV has a melting endothermic peak at 224.7±3°C.

6. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form V represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0358°, 9.5888°, 9.8806°, 15.3988°, 18.12°, 19.3591°, 20.0225°, 21.8772°, 22.9544°, 23.1765°, 23.9432°, and 27.8035°; Preferably, the X-ray powder diffraction spectrum of Form V represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0358°, 9.5888°, 9.8806°, 15.3988°, 17.4867°, 18.12°, 19.3591°, 20.0225°, 20.5607°, 21.8772°, 22.9544°, 23.1765°, 23.5735°, 23.9432°, 24.6797°, 25.3441°, 26.2773°, 27.3778°, and 27.8035°; Preferably, the X-ray powder diffraction spectrum of Form V represented by a diffraction angle of 2θ±0.2° is 9.0358°, 9.5888°, 9.8806°, 11.361°, 12.2799°, 12.8514°, 13.2758°, 15.3988°, 16.2755°, 17.1285°, 17.4867°, 18.12°, 19.3591 There are diffraction peaks at 20.0225°, 20.5607°, 21.8772°, 22.9544°, 23.1765°, 23.5735°, 23.9432°, 24.6797°, 25.3441°, 26.2773°, 27.3778°, 27.8035°, 28.8749°, 30.8579°, and 32.8505°; Preferably, the X-ray powder diffraction spectrum of Form V represented by a diffraction angle of 2θ±0.2° is 9.0358°, 9.5888°, 9.8806°, 11.361°, 12.2799°, 12.8514°, 13.2758°, 13.9999°, 15.3988°, 16.2755°, 17.1285°, 17.4867°, 18.12°, 19.3591 There are diffraction peaks at 20.0225°, 20.5607°, 21.8772°, 22.9544°, 23.1765°, 23.5735°, 23.9432°, 24.6797°, 25.3441°, 26.2773°, 27.3778°, 27.8035°, 28.8749°, 30.8579°, 32.8505°, and 34.8296°; Preferably, Form V has one or more of the following characteristics: (1) The TGA curve of Form V shows a weight loss of 9.41±1% at 150.0±3°C; (2) The TGA curve of Form V has a decomposition endothermic peak at 275.4±3°C; (3) The DSC curve of Form V has a desolvation endothermic peak at 114.4±3°C; (4) The DSC curve of Form V has a melting endothermic peak at 222.1±3℃.

7. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form VI expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1268°, 9.4721°, 11.0475°, 14.0327°, 18.2534°, 19.3437°, 20.831°, 23.3618°, 23.895°, 24.2089°, and 24.4642°; Preferably, the X-ray powder diffraction spectrum of Form VI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1268°, 9.4721°, 11.0475°, 14.0327°, 14.508°, 15.7801°, 16.1212°, 18.2534°, 19.3437°, 20.831°, 21.9229°, 22.6521°, 23.3618°, 23.895°, 24.2089°, 24.4642°, and 26.6075°; Preferably, the X-ray powder diffraction spectrum of Form VI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1268°, 9.4721°, 11.0475°, 14.0327°, 14.508°, 15.6786°, 15.7801°, 16.1212°, 18.2534°, 18.6444°, 18.9682°, 19.3437°, 20.831°, 21.9229°, 22.6521°, 23.3618°, 23.895°, 24.2089°, 24.4642°, 26.6075°, 27.1937°, and 27.5809°; Preferably, the X-ray powder diffraction spectrum of Form VI represented by a diffraction angle of 2θ±0.2° is 9.1268°, 9.4721°, 11.0475°, 12.02°, 14.0327°, 14.508°, 15.6786°, 15.7801°, 16.1212°, 18.2534°, 18.6444°, 18.9682°, 19.34 There are diffraction peaks at 37°, 20.831°, 21.9229°, 22.6521°, 23.3618°, 23.895°, 24.2089°, 24.4642°, 26.6075°, 27.1937°, 27.5809°, 28.6731°, 29.1871°, 32.192°, 33.2597°, and 35.0832°; Preferably, Form VI has one or more of the following characteristics: (1) The TGA curve of Form VI shows a weight loss of 9.82±1% at 150.0±3°C; (2) The TGA curve of Form VI has a decomposition endothermic peak at 279.0±3°C; (3) The DSC curve of Form VI has a desolvation endothermic peak at 129.6±3°C; (4) The DSC curve of Form VI has a melting endothermic peak at 224.2±3°C.

8. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form VII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 4.6919°, 9.3635°, 14.0205°, 18.7694°, and 22.6999°; Preferably, the X-ray powder diffraction spectrum of Form VII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.6919°, 9.3635°, 14.0205°, 15.3932°, 16.095°, 18.7694°, 22.6999°, and 23.3297°; Preferably, the X-ray powder diffraction spectrum of Form VII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.6919°, 8.4329°, 9.3635°, 14.0205°, 15.3932°, 16.095°, 17.2857°, 18.7694°, 20.9648°, 22.6999°, 23.3297°, and 27.0515°; Preferably, the X-ray powder diffraction spectrum of Form VII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.6919°, 8.4329°, 9.3635°, 14.0205°, 15.3932°, 16.095°, 17.2857°, 18.7694°, 20.9648°, 22.6999°, 23.3297°, 27.0515°, 29.8293°, and 32.4716°; Preferably, Form VII has one or more of the following characteristics: (1) The TGA curve of Form VII shows a weight loss of 6.77±1% at 150.0±3°C; (2) The TGA curve of Form VII has a decomposition endothermic peak at 286.8±3°C; (3) The DSC curve of Form VII has a desolvation endothermic peak at 117.4±3°C; (4) The DSC curve of Form VII has a melting endothermic peak at 223.3±3°C.

9. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form VIII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8902°, 9.818°, 15.9516°, 16.5412°, 17.851°, 19.5499°, 20.0096°, 21.4687°, 24.3685°, and 25.3691°; Preferably, the X-ray powder diffraction spectrum of Form VIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8902°, 9.818°, 15.9516°, 16.5412°, 17.851°, 18.2837°, 19.5499°, 20.0096°, 21.4687°, 21.8612°, 22.6366°, 24.3685°, 25.3691°, 25.6532°, 26.8742°, and 28.063°; Preferably, the X-ray powder diffraction spectrum of Form VIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8902°, 9.818°, 14.8678°, 15.9516°, 16.5412°, 17.851°, 18.2837°, 18.7011°, 19.5499°, 20.0096°, 21.4687°, 21.8612°, 22.6366°, 23.9934°, 24.3685°, 24.8029°, 25.3691°, 25.6532°, 26.8742°, and 28.063°; Preferably, the X-ray powder diffraction spectrum of Form VIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8902°, 9.818°, 14.4868°, 14.8678°, 15.9516°, 16.5412°, 17.851°, 18.2837°, 18.7011°, 19.5499°, 20.0096°, 21.4687°, 21.8612°, 22.6366°, 23.9934°, 24.3685°, 24.8029°, 25.3691°, 25.6532°, 26.8742°, 28.063°, 32.3583°, and 33.2506°; Preferably, Form VIII has one or more of the following characteristics: (1) The TGA curve of Form VIII shows a weight loss of 12.97±1% at 150.0±3°C; (2) The TGA curve of Form VIII has a decomposition endothermic peak at 294.7±3°C; (3) The DSC curve of Form VIII has a desolvation endothermic peak at 121.3±3°C; (4) The DSC curve of Form VIII has a melting endothermic peak at 226.0±3°C.

10. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form IX expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.6297°, 10.1401°, 10.8559°, 15.807°, 16.46°, 19.0276°, 19.3101°, 20.3323°, 20.4808°, 21.8649°, 22.9775°, 23.8504°, and 24.3408°; Preferably, the X-ray powder diffraction spectrum of Form IX represented by a diffraction angle of 2θ±0.2° is 9.6297°, 10.1401°, 10.8559°, 15.0787°, 15.807°, 16.46°, 19.0276°, 19.3101°, 20.3323°, 20.4808°, 21.8649°, There are diffraction peaks at 22.1377°, 22.4816°, 22.9775°, 23.3786°, 23.8504°, 24.3408°, 24.8941°, 25.3824°, 25.685°, 26.9466°, 27.912°, 28.2891°, 29.6722°, and 29.885°; Preferably, the X-ray powder diffraction spectrum of Form IX represented by a diffraction angle of 2θ±0.2° is 9.6297°, 10.1401°, 10.8559°, 13.8649°, 15.0787°, 15.807°, 16.46°, 17.5469°, 18.0559°, 19.0276°, 19.3101°, 20.3323°, 20.4808°, 21.8649°, 22.1 There are diffraction peaks at 377°, 22.4816°, 22.9775°, 23.3786°, 23.8504°, 24.3408°, 24.8941°, 25.3824°, 25.685°, 26.4906°, 26.9466°, 27.912°, 28.2891°, 29.6722°, 29.885°, 31.0229°, 31.468°, and 31.9828°; Preferably, the X-ray powder diffraction spectrum of Form IX represented by a diffraction angle of 2θ±0.2° is 7.8956°, 9.6297°, 10.1401°, 10.8559°, 12.1534°, 13.1811°, 13.8649°, 15.0787°, 15.807°, 16.46°, 17.5469°, 18.0559°, 19.0276°, 19.3101°, 20.3323°, 20.4808°, 21.8649°, 22.1377°, There are diffraction peaks at 22.4816°, 22.9775°, 23.3786°, 23.8504°, 24.3408°, 24.8941°, 25.3824°, 25.685°, 26.4906°, 26.9466°, 27.912°, 28.2891°, 29.6722°, 29.885°, 31.0229°, 31.468°, 31.9828°, 33.1869°, 34.2335°, 36.6216°, and 38.5212°; Preferably, Form IX has one or more of the following characteristics: (1) The TGA curve of Form IX shows a weight loss of 8.19±1% ​​at 150.0±3°C; (2) The TGA curve of Form IX has a decomposition endothermic peak at 273.0±3°C; (3) The DSC curve of Form IX has a desolvation endothermic peak at 114.3±3°C; (4) The DSC curve of Form IX has a melting endothermic peak at 222.6±3°C.

11. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form X represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0067°, 9.1811°, 9.6511°, 16.4799°, 17.8184°, 18.4803°, 19.3685°, 20.9226°, 21.5952°, 22.1082°, 22.6517°, 24.0245°, 25.5636°, and 30.2049°; Preferably, the X-ray powder diffraction spectrum of Form X represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0067°, 9.1811°, 9.6511°, 12.4199°, 13.6572°, 16.4799°, 17.8184°, 18.4803°, 19.3685°, 19.9298°, 20.9226°, 21.5952°, 22.1082°, 22.6517°, 24.0245°, 25.5636°, 26.7415°, 27.8212°, 29.0343°, and 30.2049°; Preferably, the X-ray powder diffraction spectrum of Form X represented by a diffraction angle of 2θ±0.2° is 9.0067°, 9.1811°, 9.6511°, 10.4715°, 12.4199°, 13.2215°, 13.6572°, 15.3908°, 15.7063°, 16.4799°, 17.0879°, 17.818 There are diffraction peaks at 4°, 18.4803°, 19.3685°, 19.9298°, 20.9226°, 21.5952°, 22.1082°, 22.6517°, 24.0245°, 25.5636°, 26.7415°, 27.8212°, 29.0343°, 30.2049°, and 31.6775°; Preferably, the X-ray powder diffraction spectrum of Form X represented by a diffraction angle of 2θ±0.2° is 9.0067°, 9.1811°, 9.6511°, 10.4715°, 12.4199°, 13.2215°, 13.6572°, 15.3908°, 15.7063°, 16.4799°, 17.0879°, 17.8184°, 18.480 There are diffraction peaks at 3°, 19.3685°, 19.9298°, 20.9226°, 21.5952°, 22.1082°, 22.6517°, 24.0245°, 25.5636°, 26.7415°, 27.8212°, 29.0343°, 30.2049°, 31.6775°, 33.1822°, and 35.4315°; Preferably, the crystal form X has one or more of the following characteristics: (1) The TGA curve of Form X shows a weight loss of 4.77±1% at 150.0±3°C; (2) The TGA curve of Form X has a decomposition endothermic peak at 281.5±3°C; (3) The DSC curve of Form X has a desolvation endothermic peak at 119.6±3°C; (4) The DSC curve of Form X has a melting endothermic peak at 224.3±3°C.

12. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XI expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5285°, 8.1617°, 9.1043°, 10.1559°, 13.5418°, 16.6487°, 18.2041°, 19.1824°, 19.6305°, 21.3619°, 22.7723°, 22.909°, 23.7944°, 25.502°, 25.9827°, and 26.2473°; Preferably, the X-ray powder diffraction spectrum of Form XI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5285°, 7.3628°, 8.1617°, 9.1043°, 9.4879°, 10.1559°, 13.0572°, 13.3712°, 13.5418°, 16.6487°, 18.2041°, 19.1824°, 19.6305°, 20.3145°, 21.3619°, 22.7723°, 22.909°, 23.7944°, 24.9466°, 25.502°, 25.9827°, and 26.2473°; Preferably, the X-ray powder diffraction spectrum of Form XI represented by a diffraction angle of 2θ±0.2° is 5.9933°, 6.5285°, 7.3628°, 7.5638°, 8.1617°, 9.1043°, 9.4879°, 10.1559°, 13.0572°, 13.3712°, 13.5418°, 16.3001°, 16.6487°, 1 There are diffraction peaks at 7.0183°, 17.799°, 18.2041°, 19.1824°, 19.6305°, 20.3145°, 21.3619°, 22.1595°, 22.7723°, 22.909°, 23.7944°, 24.9466°, 25.502°, 25.9827°, 26.2473°, and 27.5388°; Preferably, the X-ray powder diffraction spectrum of Form XI represented by a diffraction angle of 2θ±0.2° is 5.9933°, 6.5285°, 7.3628°, 7.5638°, 8.1617°, 9.1043°, 9.4879°, 10.1559°, 10.8344°, 13.0572°, 13.3712°, 13.5418°, 14.4054°, 15.211°, 15.96°, 16.3001°, 16. There are diffraction peaks at 6487°, 17.0183°, 17.799°, 18.2041°, 19.1824°, 19.6305°, 20.3145°, 21.3619°, 22.1595°, 22.7723°, 22.909°, 23.7944°, 24.9466°, 25.502°, 25.9827°, 26.2473°, 27.5388°, 31.9424°, and 36.0309°; Preferably, Form XI has one or more of the following characteristics: (1) The TGA curve of Form XI shows a weight loss of 6.73±1% at 150.0±3°C; (2) The TGA curve of Form XI has a decomposition endothermic peak at 276.4±3°C; (3) The DSC curve of Form XI has a desolvation endothermic peak at 103.3±3°C; (4) The DSC curve of Form XI has a melting endothermic peak at 222.6±3°C.

13. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0648°, 17.9771°, 19.4221°, 19.8351°, 22.9163°, and 24.0604°; Preferably, the X-ray powder diffraction spectrum of Form XII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0648°, 14.6209°, 16.3618°, 17.9771°, 19.4221°, 19.8351°, 22.9163°, and 24.0604°; Preferably, the X-ray powder diffraction spectrum of Form XII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0648°, 14.6209°, 15.2996°, 16.3618°, 17.9771°, 19.4221°, 19.8351°, 22.9163°, and 24.0604°; Preferably, the X-ray powder diffraction spectrum of Form XII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0648°, 10.3029°, 14.6209°, 15.2996°, 16.3618°, 17.9771°, 19.4221°, 19.8351°, 22.9163°, 24.0604°, and 27.8066°; Preferably, Form XII has one or more of the following characteristics: (1) The TGA curve of Form XII shows a weight loss of 7.91±1% at 120.0±3°C; (2) The TGA curve of Form XII has a decomposition endothermic peak at 275.4±3°C; (3) The DSC curve of Form XII has desolvation endothermic peaks at 97.5±3°C and 145.7±3°C; (4) The DSC curve of Form XII has a melting endothermic peak at 222.9±3°C.

14. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XIII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9947°, 7.9653°, 11.9493°, 13.0858°, 18.0925°, 23.1188°, 24.3969°, 25.2526°, 25.971°, and 26.7208°; Preferably, the X-ray powder diffraction spectrum of Form XIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9947°, 7.9653°, 8.9989°, 11.9493°, 13.0858°, 17.1229°, 18.0925°, 23.1188°, 23.7992°, 24.3969°, 25.2526°, 25.971°, 26.7208°, and 28.1045°; Preferably, the X-ray powder diffraction spectrum of Form XIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9947°, 7.9653°, 8.9989°, 10.5616°, 11.9493°, 13.0858°, 17.1229°, 18.0925°, 23.1188°, 23.7992°, 24.3969°, 25.2526°, 25.971°, 26.7208°, and 28.1045°; Preferably, the X-ray powder diffraction spectrum of Form XIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9947°, 7.9653°, 8.9989°, 10.5616°, 11.9493°, 13.0858°, 15.2983°, 17.1229°, 18.0925°, 23.1188°, 23.7992°, 24.3969°, 25.2526°, 25.971°, 26.7208°, 28.1045°, and 31.1848°; Preferably, Form XIII has one or more of the following characteristics: (1) The TGA curve of Form XIII shows a weight loss of 2.74±1% at 150.0±3°C; (2) The TGA curve of Form XIII has a decomposition endothermic peak at 251.1±3°C; (3) The DSC curve of Form XIII has desolvation endothermic peaks at 69.9±3°C and 101.5±3°C; (4) The DSC curve of Form XIII has a melting endothermic peak at 221.9±3°C.

15. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XIV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.746°, 8.9487°, 9.5388°, 14.0763°, 16.3184°, 16.5286°, 17.2373°, 18.3355°, 19.1287°, 19.3844°, 20.1885°, 21.4895°, 23.5043°, 23.8672°, 24.9351°, 25.1009°, 25.3026°, and 26.7261°; Preferably, the X-ray powder diffraction spectrum of Form XIV represented by a diffraction angle of 2θ±0.2° is 8.746°, 8.9487°, 9.5388°, 14.0763°, 14.9162°, 16.3184°, 16.5286°, 17.2373°, 17.9255°, 18.3355°, 18.6382°, 18.9497°, 19.1287°, There are diffraction peaks at 19.3844°, 20.1885°, 21.4895°, 21.7479°, 22.6605°, 22.813°, 23.5043°, 23.8672°, 24.9351°, 25.1009°, 25.3026°, 26.1261°, 26.7261°, 31.4344°, 31.8331°, and 33.1575°; Preferably, the X-ray powder diffraction spectrum of Form XIV represented by a diffraction angle of 2θ±0.2° is 8.746°, 8.9487°, 9.5388°, 14.0763°, 14.9162°, 15.0777°, 16.3184°, 16.5286°, 17.2373°, 17.5152°, 17.7266°, 17.9255°, 18.3355°, 18.6382°, 18.9497°, 19.1287°, 19.3844°, 19.8064°, 20.1 There are diffraction peaks at 885°, 21.4895°, 21.7479°, 22.6605°, 22.813°, 23.5043°, 23.8672°, 24.9351°, 25.1009°, 25.3026°, 25.708°, 26.1261°, 26.7261°, 27.0206°, 28.8713°, 29.2053°, 29.7983°, 30.142°, 30.4013°, 31.4344°, 31.8331°, and 33.1575°; Preferably, the X-ray powder diffraction spectrum of Form XIV represented by a diffraction angle of 2θ±0.2° is 8.746°, 8.9487°, 9.5388°, 14.0763°, 14.9162°, 15.0777°, 16.3184°, 16.5286°, 17.2373°, 17.5152°, 17.7266°, 17.9255°, 18.3355°, 18.6382°, 18.9497°, 19.1287°, 19.3844°, 19.8064°, 20.1885°, 21.4895°, 21.7479°, 22.6605°, 22. There are diffraction peaks at .813°, 23.5043°, 23.8672°, 24.9351°, 25.1009°, 25.3026°, 25.708°, 26.1261°, 26.7261°, 27.0206°, 28.8713°, 29.2053°, 29.7983°, 30.142°, 30.4013°, 31.4344°, 31.8331°, 32.6225°, 33.1575°, 33.985°, 34.8527°, 35.8313°, 36.2587°, 37.138°, 37.74°, and 38.7228°; Preferably, Form XIV has one or more of the following characteristics: (1) The TGA curve of Form XIV shows a weight loss of 18.92±1% at 200.0±3°C; (2) The TGA curve of Form XIV has a decomposition endothermic peak at 287.3±3°C; (3) The DSC curve of Form XIV has a desolvation endothermic peak at 144.2±3°C; (4) The DSC curve of Form XIV has a melting endothermic peak at 222.5±3°C.

16. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9849°, 9.7141°, 9.8357°, 15.6953°, 16.302°, 18.0068°, 18.4092°, 19.7077°, 21.1974°, 22.0516°, 23.9004°, and 25.9115°; Preferably, the X-ray powder diffraction spectrum of Form XV represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.9849°, 9.7141°, 9.8357°, 12.518°, 15.6953°, 16.302°, 16.5586°, 18.0068°, 18.4092°, 19.163°, 19.7077°, 21.1974°, 22.0516°, 22.5972°, 23.9004°, 24.5702°, 25.9115°, and 30.0833°; Preferably, the X-ray powder diffraction spectrum of Form XV represented by a diffraction angle of 2θ±0.2° is 8.9849°, 9.1887°, 9.7141°, 9.8357°, 10.5106°, 12.518°, 13.5884°, 15.6953°, 16.302°, 16.5586°, 17.287°, 18 There are diffraction peaks at .0068°, 18.4092°, 19.163°, 19.7077°, 20.7121°, 21.1974°, 22.0516°, 22.5972°, 23.9004°, 24.5702°, 25.9115°, 27.714°, 29.2898°, and 30.0833°; Preferably, the X-ray powder diffraction spectrum of Form XV represented by a diffraction angle of 2θ±0.2° is 8.9849°, 9.1887°, 9.7141°, 9.8357°, 10.5106°, 10.97°, 12.518°, 13.5884°, 15.6953°, 16.302°, 16.5586°, 17.287°, 18.0068°, 18.4092 There are diffraction peaks at 14.7°, 15.7°, 20.7121°, 21.1974°, 22.0516°, 22.5972°, 23.9004°, 24.5702°, 25.9115°, 27.714°, 29.2898°, 30.0833°, 30.7723°, 31.6746°, 32.683°, and 38.0187°; Preferably, Form XV has one or more of the following characteristics: (1) The TGA curve of Form XV shows a weight loss of 10.41±1% at 200.0±3°C; (2) The TGA curve of Form XV has a decomposition endothermic peak at 270.0±3°C; (3) The DSC curve of Form XV has a desolvation endothermic peak at 150.9±3°C; (4) The DSC curve of Form XV has a melting endothermic peak at 222.6±3℃.

17. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XVI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7733°, 10.5581°, 15.6149°, 16.4871°, 18.6864°, 19.121°, 19.5957°, 20.9453°, 21.878°, 22.2877°, 24.2135°, 24.6459°, 26.522°, and 28.023°; Preferably, the X-ray powder diffraction spectrum of Form XVI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7733°, 10.5581°, 15.6149°, 16.4871°, 18.6864°, 19.121°, 19.5957°, 20.9453°, 21.5841°, 21.878°, 22.2877°, 22.579°, 23.6036°, 24.2135°, 24.6459°, 25.3263°, 26.522°, 28.023°, and 28.5495°; Preferably, the X-ray powder diffraction spectrum of Form XVI represented by a diffraction angle of 2θ±0.2° is 9.7733°, 10.5581°, 10.8953°, 15.6149°, 16.4871°, 18.6864°, 18.8771°, 19.121°, 19.5957°, 20.2442°, 20.9453°, 21.584 There are diffraction peaks at 1°, 21.878°, 22.2877°, 22.579°, 23.0691°, 23.4112°, 23.6036°, 24.2135°, 24.6459°, 25.3263°, 26.17°, 26.522°, 28.023°, 28.5495°, 29.7362°, and 31.6608°; Preferably, the X-ray powder diffraction spectrum of Form XVI represented by a diffraction angle of 2θ±0.2° is 9.7733°, 10.5581°, 10.8953°, 14.1974°, 15.6149°, 16.0124°, 16.4871°, 17.279°, 17.6191°, 18.6864°, 18.8771°, 19.121°, 19.5957°, 20.2442°, 20.9453°, 21.584 There are diffraction peaks at 1°, 21.878°, 22.2877°, 22.579°, 23.0691°, 23.4112°, 23.6036°, 24.2135°, 24.6459°, 25.3263°, 26.17°, 26.522°, 28.023°, 28.5495°, 29.7362°, 31.6608°, 32.712°, 33.2065°, 34.4688°, and 37.8656°; Preferably, Form XVI has one or more of the following characteristics: (1) The TGA curve of Form XVI shows a weight loss of 8.51±1% at 150.0±3°C; (2) The TGA curve of Form XVI has a decomposition endothermic peak at 276.9±3°C; (3) The DSC curve of Form XVI has a desolvation endothermic peak at 115.7±3°C; (4) The DSC curve of Form XVI has a melting endothermic peak at 222.7±3°C.

18. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XVII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9382°, 9.4506°, 11.7177°, 15.6252°, 17.1262°, 18.9052°, 19.4649°, 20.847°, 21.9599°, and 23.4901°; Preferably, the X-ray powder diffraction spectrum of Form XVII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9382°, 9.4506°, 11.7177°, 15.6252°, 17.1262°, 18.9052°, 19.4649°, 20.847°, 21.4135°, 21.9599°, 22.8698°, 23.4901°, 24.5954°, 26.0691°, 28.51°, and 31.4763°; Preferably, the X-ray powder diffraction spectrum of Form XVII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.9382°, 9.4506°, 9.7497°, 11.7177°, 15.0611°, 15.6252°, 17.1262°, 18.9052°, 19.4649°, 20.3109°, 20.847°, 21.4135°, 21.9599°, 22.8698°, 23.4901°, 24.5954°, 26.0691°, 26.689°, 28.51°, and 31.4763°; Preferably, the X-ray powder diffraction spectrum of Form XVII represented by a diffraction angle of 2θ±0.2° is 3.9382°, 9.4506°, 9.7497°, 11.7177°, 13.0266°, 15.0611°, 15.6252°, 17.1262°, 18.9052°, 19.4649°, 20.3109°, 20.847 There are diffraction peaks at 21.4135°, 21.9599°, 22.8698°, 23.4901°, 24.5954°, 26.0691°, 26.689°, 28.51°, 30.6955°, 31.4763°, 32.5073°, 35.5318°, 36.311°, 37.2464°, and 39.6521°; Preferably, Form XVII has one or more of the following characteristics: (1) The TGA curve of Form XVII shows a weight loss of 15.13±1% at 200.0±3°C; (2) The TGA curve of Form XVII has a decomposition endothermic peak at 316.6±3°C; (3) The DSC curve of Form XVII has a desolvation endothermic peak at 146.9±3°C; (4) The DSC curve of Form XVII has a melting endothermic peak at 223.4±3°C.

19. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XVIII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0852°, 9.9044°, 18.2229°, 18.657°, 19.8834°, 25.403°, 27.4648°, 27.765°, and 28.6285°; Preferably, the X-ray powder diffraction spectrum of Form XVIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0852°, 9.696°, 9.9044°, 15.5095°, 18.2229°, 18.657°, 19.8834°, 25.403°, 27.4648°, 27.765°, 28.6285°, and 37.173°; Preferably, the X-ray powder diffraction spectrum of Form XVIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0852°, 9.696°, 9.9044°, 15.5095°, 18.2229°, 18.657°, 19.8834°, 22.9326°, 25.403°, 27.4648°, 27.765°, 28.6285°, 29.9839°, 37.173°, and 38.8939°; Preferably, the X-ray powder diffraction spectrum of Form XVIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.0852°, 9.696°, 9.9044°, 12.0086°, 15.5095°, 18.2229°, 18.657°, 19.8834°, 22.9326°, 25.403°, 26.3549°, 27.4648°, 27.765°, 28.6285°, 29.9839°, 37.173°, and 38.8939°; Preferably, Form XVIII has one or more of the following characteristics: (1) The TGA curve of Form XVIII shows a weight loss of 5.30±1% at 170.0±3°C; (2) The TGA curve of Form XVIII has a decomposition endothermic peak at 284.8±3°C; (3) The DSC curve of Form XVIII has a desolvation endothermic peak at 150.1±3°C; (4) The DSC curve of Form XVIII has a melting endothermic peak at 224.6±3°C.

20. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XIX expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.2306°, 9.7843°, 10.5597°, 15.2185°, 16.7197°, 18.6635°, 19.642°, 21.6489°, 24.2523°, and 25.9223°; Preferably, the X-ray powder diffraction spectrum of Form XIX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2778°, 8.2306°, 9.1956°, 9.7843°, 10.5597°, 15.2185°, 16.7197°, 18.6635°, 19.642°, 21.6489°, 22.8118°, 24.2523°, 25.9223°, and 29.7113°; Preferably, the X-ray powder diffraction spectrum of Form XIX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2778°, 8.2306°, 9.1956°, 9.7843°, 10.5597°, 15.2185°, 16.7197°, 18.6635°, 19.642°, 21.6489°, 22.8118°, 24.2523°, 25.9223°, 27.8768°, and 29.7113°; Preferably, the X-ray powder diffraction spectrum of Form XIX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2778°, 8.2306°, 9.1956°, 9.7843°, 10.5597°, 12.8908°, 15.2185°, 16.7197°, 18.6635°, 19.642°, 21.6489°, 22.8118°, 24.2523°, 25.9223°, 27.8768°, and 29.7113°; Preferably, Form XIX has one or more of the following characteristics: (1) The TGA curve of Form XIX shows a weight loss of 5.30±1% at 150±3°C; (2) The TGA curve of Form XIX has a decomposition endothermic peak at 275.5±3°C; (3) The DSC curve of Form XIX has desolvation endothermic peaks at 105.2±3°C and 118.9±3°C; (4) The DSC curve of Form XIX has a melting endothermic peak at 222.6±3°C.

21. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XX expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.1562°, 16.3732°, 19.4177°, 19.9051°, 21.765°, 24.0195°, 24.6421°, and 27.6839°; Preferably, the X-ray powder diffraction spectrum of Form XX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.9295°, 8.1562°, 9.8697°, 15.8946°, 16.3732°, 19.4177°, 19.9051°, 21.1077°, 21.765°, 24.0195°, 24.6421°, 25.8571°, 27.6839°, and 28.4482°; Preferably, the X-ray powder diffraction spectrum of Form XX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.9295°, 6.2823°, 8.1562°, 9.8697°, 11.9239°, 13.7136°, 15.8946°, 16.3732°, 19.4177°, 19.9051°, 21.1077°, 21.765°, 24.0195°, 24.6421°, 25.8571°, 27.6839°, and 28.4482°; Preferably, the X-ray powder diffraction spectrum of Form XX represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 4.9295°, 6.2823°, 8.1562°, 9.8697°, 11.9239°, 13.7136°, 15.8946°, 16.3732°, 19.4177°, 19.9051°, 21.1077°, 21.765°, 24.0195°, 24.6421°, 25.8571°, 27.6839°, 28.4482°, 32.1403°, and 33.0643°; Preferably, the crystalline form XX has one or more of the following characteristics: (1) The TGA curve of Form XX shows a weight loss of 21.50±1% at 150±3°C; (2) The TGA curve of Form XX has a decomposition endothermic peak at 307.5±3°C; (3) The DSC curve of Form XX has a desolvation endothermic peak at 96.4±3°C; (4) The DSC curve of Form XX has a melting endothermic peak at 223.5±3°C.

22. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XXI represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1247°, 9.4385°, 15.2708°, 16.1429°, 17.3222°, 17.6586°, 18.3906°, 18.734°, 19.217°, 20.0426°, 20.8807°, 21.3881°, 23.1609°, 23.5369°, 24.106°, 24.5057°, 26.0111°, and 26.2379°; Preferably, the X-ray powder diffraction spectrum of Form XXI expressed at a diffraction angle of 2θ±0.2° is 8.2582°, 9.1247°, 9.4385°, 11.8388°, 13.0734°, 15.2708°, 15.6112°, 16.1429°, 17.3222°, 17.6586°, 18.1167°, 18.3906°, 18.734°, 19.2 There are diffraction peaks at 17°, 20.0426°, 20.8807°, 21.3881°, 22.0439°, 22.4864°, 23.1609°, 23.5369°, 23.8132°, 24.106°, 24.5057°, 24.8877°, 26.0111°, 26.2379°, 26.6445°, 27.8858°, and 28.7599°; Preferably, the X-ray powder diffraction spectrum of Form XXI represented by a diffraction angle of 2θ±0.2° is 8.2582°, 9.1247°, 9.4385°, 10.3908°, 11.8388°, 13.0734°, 14.5829°, 15.2708°, 15.6112°, 16.1429°, 17.3222°, 17.6586°, 18.1167°, 18.3906°, 18.734°, 19.217°, 20.0426°, There are diffraction peaks at 20.8807°, 21.3881°, 22.0439°, 22.4864°, 23.1609°, 23.5369°, 23.8132°, 24.106°, 24.5057°, 24.8877°, 26.0111°, 26.2379°, 26.6445°, 27.1343°, 27.8858°, 28.7599°, 29.3559°, 30.0389°, 30.801°, and 31.824°; Preferably, the X-ray powder diffraction spectrum of Form XXI represented by a diffraction angle of 2θ±0.2° is 8.2582°, 9.1247°, 9.4385°, 10.3908°, 10.8322°, 11.8388°, 13.0734°, 14.5829°, 15.2708°, 15.6112°, 16.1429°, 17.3222°, 17.6586°, 18.1167°, 18.3906°, 18.734°, 19.217°, 20.0426°, There are diffraction peaks at 20.8807°, 21.3881°, 22.0439°, 22.4864°, 23.1609°, 23.5369°, 23.8132°, 24.106°, 24.5057°, 24.8877°, 26.0111°, 26.2379°, 26.6445°, 27.1343°, 27.8858°, 28.7599°, 29.3559°, 30.0389°, 30.801°, 31.824°, and 32.6367°.

23. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XXII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.303°, 8.8753°, 9.3235°, 10.4306°, 15.5408°, 16.9429°, 17.56°, 17.773°, 18.6982°, 19.0572°, 20.9194°, 21.1192°, 21.383°, 23.8992°, 24.1642°, 26.0356°, and 26.6018°; Preferably, the X-ray powder diffraction spectrum of Form XXII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.303°, 8.8753°, 9.3235°, 10.4306°, 13.6912°, 15.5408°, 16.9429°, 17.56°, 17.773°, 18.6982°, 19.0572°, 19.4617°, 20.9194°, 21.1192°, 21.383°, 21.9111°, 22.4002°, 23.8992°, 24.1642°, 24.5292°, 26.0356°, 26.6018°, and 27.4938°; Preferably, the X-ray powder diffraction spectrum of Form XXII represented by a diffraction angle of 2θ±0.2° is 8.303°, 8.8753°, 9.3235°, 10.4306°, 11.3337°, 12.9434°, 13.6912°, 15.5408°, 16.9429°, 17.56°, 17.773°, 18.6982°, 19.0572°, 1 There are diffraction peaks at 9.4617°, 20.9194°, 21.1192°, 21.383°, 21.9111°, 22.4002°, 23.0249°, 23.8992°, 24.1642°, 24.5292°, 26.0356°, 26.6018°, 27.4938°, 28.1751°, 28.5674°, and 29.7642°; Preferably, the X-ray powder diffraction spectrum of Form XXII represented by a diffraction angle of 2θ±0.2° is 8.303°, 8.8753°, 9.3235°, 10.4306°, 11.3337°, 12.2858°, 12.9434°, 13.6912°, 14.6208°, 15.5408°, 15.8979°, 16.279°, 16.9429°, 17.56°, 17.773°, 18.698 There are diffraction peaks at 2°, 19.0572°, 19.4617°, 20.9194°, 21.1192°, 21.383°, 21.9111°, 22.4002°, 23.0249°, 23.8992°, 24.1642°, 24.5292°, 26.0356°, 26.6018°, 27.4938°, 28.1751°, 28.5674°, 29.7642°, and 31.2811°.

24. The polymorph of the sGC agonist according to claim 1, characterized in that The X-ray powder diffraction spectrum of Form XXIII expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7799°, 10.8113°, 11.1486°, 15.6173°, 16.2004°, 18.8244°, 20.2031°, 20.6918°, and 25.325°; Preferably, the X-ray powder diffraction spectrum of Form XXIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7799°, 10.8113°, 11.1486°, 12.8168°, 15.6173°, 16.2004°, 18.8244°, 19.2693°, 20.2031°, 20.6918°, and 25.325°; Preferably, the X-ray powder diffraction spectrum of Form XXIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7799°, 10.8113°, 11.1486°, 12.8168°, 14.2512°, 15.6173°, 16.2004°, 17.7301°, 18.8244°, 19.2693°, 20.2031°, 20.6918°, and 25.325°; Preferably, the X-ray powder diffraction spectrum of Form XXIII represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7799°, 10.8113°, 11.1486°, 12.8168°, 14.2512°, 15.6173°, 16.2004°, 17.7301°, 18.8244°, 19.2693°, 20.2031°, 20.6918°, 22.0426°, and 25.325°; Preferably, Form XXIII has one or more of the following characteristics: (1) The TGA curve of Form XXIII shows a weight loss of 2.28±1% at 150±3°C; (2) The TGA curve of Form XXIII has a decomposition endothermic peak at 264.8±3°C; (3) The DSC curve of Form XXIII has a melting endothermic peak at 221.6±3°C.

25. A method for preparing a polymorph of the sGC agonist according to any one of claims 1 to 24, characterized in that Use one of the following methods: Method 1: Add compound I to a solvent, suspend and stir at 0-50°C for 4-7 days, centrifuge, remove the supernatant, and vacuum dry to obtain the compound I; Method 2: Add compound I to a solvent and shake for 1-2 days, centrifuge, remove the supernatant, and vacuum dry to obtain; Method 3: Add compound I to a good solvent and stir to dissolve, add the resulting solution to an anti-solvent and stir, filter, wash the resulting filter cake, and dry to obtain; Method 4: Add compound I to a good solvent to dissolve, filter, add anti-solvent to the filtrate, stir, centrifuge, remove the supernatant, and vacuum dry to obtain; Method 5: Add compound I to a solvent to dissolve, filter, place the filtrate in an anti-solvent environment for gas-liquid diffusion, centrifuge, remove the supernatant, and vacuum dry to obtain; Method 6: Place compound I in a solvent environment for gas-solid diffusion to obtain; Method 7: Compound I is added to a solvent, suspended and stirred at 0-50° C. for 4-7 days, centrifuged, the supernatant is removed, vacuum dried, and heat treated under nitrogen protection to obtain the product.

26. The method for preparing the polymorphic form of the sGC agonist according to claim 25, characterized in that The solvent is one or both of water and organic solvents; the organic solvent is one or more of alcohol, chloroalkane, ketone, ether, cyclic ether, ester, alkane, benzene, sulfoxide or amide; the good solvent is one or more of dimethyl sulfoxide, methanol, ethanol, tetrahydrofuran or N,N-dimethylformamide; the anti-solvent is one or more of isopropanol, acetone, ethyl acetate, isopropyl acetate, methyl acetate, acetonitrile, methyl tert-butyl ether, toluene, dichloromethane, water or n-hexane.

27. A use of a polymorph of a sGC agonist according to any one of claims 1 to 24, characterized in that The pharmaceutical composition comprises at least one of the following: form I, form II, form III, form IV, form V, form VI, form VII, form VIII, form IX, form X, form XI, form XII, form XIII, form XIV, form XV, form XVI, form XVII, form XVIII, form XIX, form XX, form XXI, form XXII or form XXIII, and a pharmaceutically acceptable carrier.

28. A use of a polymorph of a sGC agonist according to any one of claims 1 to 24, characterized in that Used to prepare medicines for treating lung diseases.

29. Use of the polymorphic form of the sGC agonist according to claim 28, characterized in that Pulmonary disease is pulmonary hypertension or pulmonary fibrosis.

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