Salt form and polycrystalline form of allopregnanolone derivative, preparation method therefor, and use thereof
AssigneeNanjing Minova Pharmaceutical Co., Ltd.
InventorsFei LIU, Xianchao LI, Gang WU, Xin ZHAO, Chenggang LIN, Chaoqun LENG
Life of this patent
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Abstract
Salt forms of an allopregnanolone derivative includes hydrochloride, phosphate, L-malate, maleate, p-toluenesulfonate, benzoate and the like. Crystalline forms and amorphous forms of the hydrochloride of the allopregnanolone derivative include a crystal form I, a crystal form II, a crystal form III, and a crystal form IV. Both the hydrochloride and the phosphate of the allopregnanolone derivative have good stability and are easy to prepare.
Claims12
A pharmaceutically acceptable salt of compound 1 shown below, wherein the pharmaceutically acceptable salt is a salt formed by compound 1 and an organic acid or inorganic acid,
- preferably, the pharmaceutically acceptable salt is selected from hydrochloride, phosphate, benzoate, p-toluenesulfonate, malate, acetate, benzenesulfonate, and maleate.
A crystalline form of compound 2, wherein the crystalline form is a crystalline form I, wherein the crystalline form I has an X-ray powder diffraction pattern comprising characteristic peaks at one or more of 2θ angles of 6.3±0.2°, 10.9-0.2°, 13.3-0.2°, 13.5±0.2°, 15.1±0.2°, and 17.8±0.2°;
- preferably, the crystalline form I has an X-ray powder diffraction pattern comprising characteristic peaks at one or more of 2θ angles of 6.3±0.2°, 10.9±0.2°, 13.3±0.2°, 13.5±0.2°, 14.2±0.2°, 15.1±0.2°, 15.8±0.2°, 17.4±0.2°, 17.8±0.2°, 20.9±0.2°, and 24.0±0.2°;
- further preferably, the crystalline form I has an XRPD pattern substantially as shown in FIG. 1;
- wherein the crystalline form is a crystalline form II, wherein the crystalline form II has an X-ray powder diffraction pattern comprising characteristic peaks at one or more of 2θ angles of 4.0±0.2°, 10.6±0.2°, 13.9±0.2°, 14.5±0.2°, 18.4±0.2°, and 21.3±0.2°;
- preferably, the crystalline form II has an X-ray powder diffraction pattern comprising characteristic peaks at one or more of 2θ angles of 4.0±0.2°, 10.6±0.2°, 13.0±0.2°, 13.9±0.2°, 14.5±0.2°, 18.4±0.2°, and 21.3±0.2°;
- further preferably, the crystalline form II has an XRPD pattern substantially as shown in FIG. 5;
- wherein the crystalline form is a crystalline form III, wherein the crystalline form III has an X-ray powder diffraction pattern comprising characteristic peaks at one or more of 2θ angles of 3.4±0.2°, 9.8±0.2°, 12.1±0.2°, 13.1±0.2°, 16.4±0.2°, and 21.9±0.2°;
- preferably, the crystalline form III has an X-ray powder diffraction pattern comprising characteristic peaks at one or more of 2θ angles of 3.4±0.2°, 9.8±0.2°, 11.4±0.2°, 12.1±0.2°, 13.1±0.2°, 14.7±0.2°, 16.4±0.2°, 19.9±0.2°, and 21.9±0.2°;
- further preferably, the crystalline form III has an XRPD pattern substantially as shown in FIG. 9;
- or
- wherein the crystalline form is a crystalline form IV, wherein the crystalline form IV has an X-ray powder diffraction pattern comprising characteristic peaks at one or more of 2θ angles of 10.7±0.2°, 11.4±0.2°, 12.9±0.2°, 13.3±0.2°, 16.1±0.2°, 17.6±0.2°, and 19.9±0.2°;
- preferably, the crystalline form IV has an X-ray powder diffraction pattern comprising characteristic peaks at one or more of 2θ angles of 10.7±0.2°, 11.4±0.2°, 12.0±0.2°, 12.9±0.2°, 13.3±0.2°, 16.1±0.2°, 17.6±0.2°, 19.1±0.2°, and 19.9±0.2°;
- further preferably, the crystalline form IV has an XRPD pattern substantially as shown in FIG. 11.
5-7. (canceled)
An amorphous form of compound 2, wherein the amorphous form has an XRPD pattern substantially as shown in FIG. 13;
Dependencies are inferred from the claim text.