Optimized synthesis of pure, non-polymorphic, crystalline bile acids with defined particle size

摘要

Disclosed is a method for the preparation of a pure polymorph of Nor-UDCA (norursodeoxycholic) or Bis-nor-UDCA (bis-nor-ursodeoxycholic acid), or of a pharmaceutically acceptable salt thereof, comprising the following steps: crystallizing the potassium salt of Nor-UDCA or Bis-nor-UDCA; and dissolving the potassium salt in a solvent (e.g., water and acetone) and acidifying the solution (e.g., to a pH of 1-2) to obtain pure Nor-UDCA or Bis-nor-UDCA. The method does not require a milling step and/or a micronization step. The pure polymorphs of Nor-UDCA (norursodeoxycholic) and Bis-nor-UDCA (bis-nor-ursodeoxycholic acid) are suitable for the treatment of bile- and liver diseases.