Crystalline forms of 5α-androstane-3β,5,6β-triol and preparation methods therefor
View Patent ↗The present invention relates to four crystalline forms (crystalline forms A, B, C and D) of 5α-androstane-3β,5,6β-triol (YC-6) and preparation methods therefor. The four crystalline forms have significant difference in their lattice parameters, 2θ values and intensity in X-ray power diffraction, and melting points, etc. The study on its polymorphism is very important for further studying its effect, bioavailability and stability.
1. A method for preparing a crystalline form of 5α-androstane-3β,5,6β-triol,
comprising:
dissolving 5α-androstane-3β,5,6β-triol in a solvent to form a mixture, with a ratio of the 5α-androstane-3β,5,6β-triol to the solvent being 1g:10˜120 mL;
heating the mixture to 50˜80° C.;
adding another solvent to dilute the mixture;
cooling the mixture; and
allowing the mixture to form a crystalline precipitate,
wherein the crystalline form is a transparent needle-shaped crystal, and belongs to monoclinic crystal system and space group P2 1 , and
wherein the crystalline form is characterized by lattice parameters of a=11.3±0.2 Å, b=7.4±0.2 Å, c=20.5±0.2 Å, α=90.0°, β=95.0±0.5°, γ=90.0°; and characterized by diffraction peaks at diffraction angle 2θ values of 4.3±0.2, 8.6±0.2, 12.9±0.2, 17.2±0.2, 21.6±0.2 degrees; and characterized by an endothermic transition temperature of 223±2° C.
2. The method of claim 1 , wherein the solvent for dissolving is acetone, ethyl acetate or ethanol, and
the solvent for diluting is the same as the solvent for dissolving or a poor solvent selected from water, hexamethylene and petroleum ether.
3. The method of claim 2 , wherein
when acetone or ethanol is used as the solvent for dissolving and water is used as the poor solvent for diluting, the mixture is diluted at a ratio of 1:2.5-5;
when acetone or ethanol is used as the solvent for dissolving and hexamethylene or petroleum ether is used as the poor solvent for diluting, the mixture is diluted at a ratio of 1:1-5;
when ethyl acetate is used as the solvent for dissolving and ethyl acetate is used as the solvent for diluting, the mixture is diluted at a ratio of 1:1-5; and
when ethyl acetate is used as the solvent for dissolving and hexamethylene or petroleum ether is used as the poor solvent for diluting, the mixture is diluted at a ratio of 1:1-5.