公开(公告)号：WO2008017278A3

公开(公告)日：2008-07-10

申请号：PCT/CZ2007000078

申请日：2007-08-09

Applicant: ZENTIVA AS ,  SVOBODA MARTIN ,  JAMPILEK JOSEF ,  KACIRKOVA MARTINA ,  TOMASEK VACLAV ,  LEHOCKY MIKULAS ,  HEJTMANKOVA LUDMILA ,  VOSATKA VACLAV

Inventor： SVOBODA MARTIN ,  JAMPILEK JOSEF ,  KACIRKOVA MARTINA ,  TOMASEK VACLAV ,  LEHOCKY MIKULAS ,  HEJTMANKOVA LUDMILA ,  VOSATKA VACLAV

IPC: C07C213/10 ,  A61K31/137 ,  C07C215/54

CPC classification number: C07C215/54 ,  C07C213/10

Abstract: A crystalline salt of 2-[(1R)-3-[bis(l-methylethyl)amino]-1-?henyl?ropyl]-4-methyl-phenol with (2R,3R)-2,3-dihydroxybutanedioic acid, known under the name R-tolterodine tartarate, wherein: a) at least 90 % of all crystals are present in a size smaller than 30 µm, b) at least 40 % of crystalline matter are smaller than 250 µm, c) the maximum size of crystals does not exceed 800 µm, d) the salt contains less than 0.1 weight % of the undesirable enantiomer S-tolterodine tartarate, e) analytical test for sulfate ashes (Pharm. Eur.) provides a value lower than 0.1%. The method of its preparation involves at least one crystallization from water. A pharmaceutical composition containing tolterodine or its pharmaceutically acceptable salts further contains a filler, a disintegrant and a lubricant, said composition being free of ions of alkaline earth metals.

Abstract translation: 2 - [（1R）-3- [双（1-甲基乙基）氨基] -1-苯基丙基] -4-甲基 - 苯酚与（2R，3R）-2,3-二羟基丁二酸的结晶盐， 以名称R-托特罗定酒石酸盐公知，其中：a）全部晶体的至少90％以小于30μm的尺寸存在，b）至少40％的晶体物质小于250μm，c）最大尺寸 的晶体不超过800μm，d）盐含有小于0.1重量％的不良对映体S-托特罗定酒石酸盐，e）硫酸盐灰分（欧洲药典）的分析测试提供的值低于0.1％。 其制备方法涉及至少一次从水中结晶。 含有托特罗定或其药学上可接受的盐的药物组合物还含有填充剂，崩解剂和润滑剂，所述组合物不含碱土金属离子。

公开(公告)号：WO2008017278B1

公开(公告)日：2008-08-28

申请号：PCT/CZ2007000078

申请日：2007-08-09

Applicant: ZENTIVA AS ,  SVOBODA MARTIN ,  JAMPILEK JOSEF ,  KACIRKOVA MARTINA ,  TOMASEK VACLAV ,  LEHOCKY MIKULAS ,  HEJTMANKOVA LUDMILA ,  VOSATKA VACLAV

Inventor： SVOBODA MARTIN ,  JAMPILEK JOSEF ,  KACIRKOVA MARTINA ,  TOMASEK VACLAV ,  LEHOCKY MIKULAS ,  HEJTMANKOVA LUDMILA ,  VOSATKA VACLAV

IPC: C07C213/10 ,  A61K31/137 ,  C07C215/54

CPC classification number: C07C215/54 ,  C07C213/10

Abstract: A crystalline salt of 2-[(1R)-3-[bis(l-methylethyl)amino]-1-?henyl?ropyl]-4-methyl-phenol with (2R,3R)-2,3-dihydroxybutanedioic acid, known under the name R-tolterodine tartarate, wherein: a) at least 90 % of all crystals are present in a size smaller than 30 µm, b) at least 40 % of crystalline matter are smaller than 250 µm, c) the maximum size of crystals does not exceed 800 µm, d) the salt contains less than 0.1 weight % of the undesirable enantiomer S-tolterodine tartarate, e) analytical test for sulfate ashes (Pharm. Eur.) provides a value lower than 0.1%. The method of its preparation involves at least one crystallization from water. A pharmaceutical composition containing tolterodine or its pharmaceutically acceptable salts further contains a filler, a disintegrant and a lubricant, said composition being free of ions of alkaline earth metals.

Abstract translation: 2 - [（1R）-3- [双（1-甲基乙基）氨基] -1-苯基乙酰基] -4-甲基 - 苯酚与（2R，3R）-2,3-二羟基丁二酸的结晶盐， 以名称R-tolterodine酒石酸盐，其中：a）至少90％的晶体以小于30μm的尺寸存在，b）至少40％的结晶物质小于250μm，c）最大尺寸 的晶体不超过800μm，d）盐含有小于0.1重量％的不需要的对映体S-托特罗定酒石酸酯，e）硫酸盐灰分析（Pharm.Eur。）的分析测试提供的值低于0.1％。 其制备方法涉及至少一种从水中的结晶。 含有托特罗定或其药学上可接受的盐的药物组合物还含有填料，崩解剂和润滑剂，所述组合物不含碱土金属的离子。

公开(公告)号：WO2008017278A2

公开(公告)日：2008-02-14

申请号：PCT/CZ2007/000078

申请日：2007-08-09

Applicant: ZENTIVA, A.S. ,  SVOBODA, Martin ,  JAMPILEK, Josef ,  KACIRKOVA, Martina ,  TOMASEK, Vaclav ,  LEHOCKY, Mikulas ,  HEJTMANKOVA, Ludmila ,  VOSATKA, Vaclav

Inventor： SVOBODA, Martin ,  JAMPILEK, Josef ,  KACIRKOVA, Martina ,  TOMASEK, Vaclav ,  LEHOCKY, Mikulas ,  HEJTMANKOVA, Ludmila ,  VOSATKA, Vaclav

IPC: C07C213/10 ,  C07C215/54 ,  A61K31/137

CPC classification number: C07C215/54 ,  C07C213/10

Abstract: A crystalline salt of 2-[(1R)-3-[bis(l-methylethyl)amino]-1-ρhenylρropyl]-4-methyl-phenol with (2R,3R)-2,3-dihydroxybutanedioic acid, known under the name R-tolterodine tartarate, wherein: a) at least 90 % of all crystals are present in a size smaller than 30 μm, b) at least 40 % of crystalline matter are smaller than 250 μm, c) the maximum size of crystals does not exceed 800 μm, d) the salt contains less than 0.1 weight % of the undesirable enantiomer S-tolterodine tartarate, e) analytical test for sulfate ashes (Pharm. Eur.) provides a value lower than 0.1%. The method of its preparation involves at least one crystallization from water. A pharmaceutical composition containing tolterodine or its pharmaceutically acceptable salts further contains a filler, a disintegrant and a lubricant, said composition being free of ions of alkaline earth metals.

Abstract translation: （2R，3R）-2,2-二甲基苯胺的2 - [（1R）-3- [双（1-甲基乙基）氨基] -1-苯基丙基] -4-甲基 - 苯酚的晶体盐， 其中：a）全部晶体的至少90％以小于30μm的尺寸存在，b）至少40％的晶体物质小于250μm， c）晶体的最大尺寸不超过800μm，d）盐含有小于0.1重量％的不希望的对映体S-托特罗定酒石酸盐，e）硫酸盐灰分（欧洲药典）的分析测试提供的值低于 0.1％。 其制备方法涉及至少一次从水中结晶。 包含托特罗定或其药学上可接受的盐的药物组合物还含有填充剂，崩解剂和润滑剂，所述组合物不含碱土金属离子。