SIEGER PETER,KEMMER DIRK,KOHLBAUER PETER,NICOLA THOMAS,RENZ MARTIN
申请号：
NZ61941307
公开号：
NZ619413A
申请日:
2007.04.30
申请国别(地区):
NZ
年份:
2015
代理人:
摘要：
Disclosed is a method of preparing a medicament (which may include a mixture of polymorphic forms A and B of linagliptin) comprising preparing anhydrous polymorph A of linagliptin (1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-5yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine), and combining the anhydrous polymorph A with one or more inert carriers, wherein said medicament contains 0.1 to 3 wt. % of anhydrous polymorph A in addition to one or more inert carriers； wherein anhydrous polymorph A is prepared by either A): (a) refluxing linagliptin in absolute ethanol and optionally filtering the mixture, (b) cooling the hot solution or the hot filtrate until crystallisation sets in, (c) diluting with a solvent such as tert.-butylmethylether, (d) suction filtering the solvent mixture and (e) drying the polymorph A at 45°C in vacuo； or B): by heating polymorph B of linagliptin or a mixture of polymorphs A and B to temperatures in excess of 40°C, wherein polymorph B is characterised by reversibly transforming into the polymorph A at a temperature of 10-40°C； wherein anhydrous polymorph A is characterised by melting at 206±3°C. Also disclosed is a method of preparing a medicament (which may include a mixture of polymorphic forms A and B of linagliptin) comprising preparing anhydrous polymorph B of linagliptin, and combining anhydrous polymorph B with one or more inert carriers, wherein said medicament contains 0.1 to 3 wt. % of anhydrous polymorph B in addition to one or more inert carriers； wherein anhydrous polymorph B is prepared by either A): (a) dissolving linagliptin in absolute ethanol and refluxing and optionally filtering the mixture, (b) cooling the hot solution or the hot filtrate for crystallisation to a temperature below 10°C, (c) diluting with a solvent such as tert-butylmethylether, (d) suction filtering the solvent mixture and (e) drying the polymorph at a temperature below 10°C in vacuo； or B): by cooling polymorph A of linagliptin or a mixture of p
