公开(公告)号：US20070112198A1

公开(公告)日：2007-05-17

申请号：US10570551

申请日：2004-09-01

申请人： Hans Petersen ,  Michael Sommer ,  Robert Dancer

发明人： Hans Petersen ,  Michael Sommer ,  Robert Dancer

IPC分类号： C07D491/02

CPC分类号： C07D498/04

摘要： The present invention relates to a new method of preparing gaboxadol (THIP), which is useful for treating sleep disorders. In particular a method of preparing THIP comprising reacting a compound of formula (8b) or a salt thereof with an acid, typically a mineral acid, to obtain THIP as an acid addition salt. The present invention also relates to several intermediates.

摘要翻译： 本发明涉及一种制备加波沙朵（THIP）的新方法，其可用于治疗睡眠障碍。 特别是制备THIP的方法，包括使式（8b）的化合物或其盐与酸（通常为无机酸）反应，得到THIP作为酸加成盐。 本发明还涉及几种中间体。

公开(公告)号：US20110046218A1

公开(公告)日：2011-02-24

申请号：US12916750

申请日：2010-11-01

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： A61K31/343 ,  C07D307/87 ,  A61P25/24

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

摘要翻译： 本发明涉及众所周知的抗抑郁药物依他普仑S-1- [3-（二甲基氨基）丙基] -1-（4-氟苯基）-1,3-二氢-5-异苯并呋喃甲腈的结晶碱，所述制剂为 碱，使用碱，草酸盐的纯化盐的制备方法，通过所述方法获得的盐和含有这些盐的制剂的方法，以及制备纯化的依他普仑游离碱或依他普仑的盐的方法， 例如草酸盐，使用氢溴酸盐，通过所述方法获得的盐和含有这些盐的制剂。 最后，本发明涉及硬度至少为22N，口服崩解时间小于120秒的可分散片剂，其包含吸附在水溶性填料上的活性药物成分，其中活性药物成分的熔点为 40-100℃的范围，以及制造这种可分散片剂的方法。

公开(公告)号：US20070021499A1

公开(公告)日：2007-01-25

申请号：US11425522

申请日：2006-06-21

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： A61K31/343 ,  C07D307/02

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

摘要翻译： 本发明涉及众所周知的抗抑郁药物依他普仑S-1- [3-（二甲基氨基）丙基] -1-（4-氟苯基）-1,3-二氢-5-异苯并呋喃甲腈的结晶碱，所述制剂为 碱，使用碱，草酸盐的纯化盐的制备方法，通过所述方法获得的盐和含有这些盐的制剂的方法，以及制备纯化的依他普仑游离碱或依他普仑的盐的方法， 例如草酸盐，使用氢溴酸盐，通过所述方法获得的盐和含有这些盐的制剂。 最后，本发明涉及硬度至少为22N，口服崩解时间小于120秒的可分散片剂，其包含吸附在水溶性填料上的活性药物成分，其中活性药物成分的熔点为 40-100℃的范围，以及制造这种可分散片剂的方法。

公开(公告)号：US07560576B2

公开(公告)日：2009-07-14

申请号：US12046984

申请日：2008-03-12

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： C07D307/00 ,  A61K31/34

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzo-furancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

摘要翻译： 本发明涉及众所周知的抗抑郁药物依他普仑S-1- [3-（二甲基氨基）丙基] -1-（4-氟苯基）-1,3-二氢-5-异苯并呋喃腈的结晶碱，其制剂 的所述碱的方法，使用碱，通过所述方法获得的盐以及含有这些盐的制剂来制备依他普仑的纯化盐如草酸盐的方法，以及制备纯化的依他普仑游离碱或其盐的方法 使用氢溴酸盐，通过所述方法获得的盐和含有这些盐的制剂，例如草酸盐。 最后，本发明涉及硬度至少为22N，口服崩解时间小于120秒的可分散片剂，其包含吸附在水溶性填料上的活性药物成分，其中活性药物成分的熔点为 40-100℃的范围，以及制造这种可分散片剂的方法。

公开(公告)号：US20080161584A1

公开(公告)日：2008-07-03

申请号：US12046999

申请日：2008-03-12

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： C07D307/87

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzo-furancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

公开(公告)号：US07390913B2

公开(公告)日：2008-06-24

申请号：US10540300

申请日：2003-12-18

申请人： Hans Petersen ,  Brian Christiansen ,  Robert Dancer ,  Rikke E. Humble

发明人： Hans Petersen ,  Brian Christiansen ,  Robert Dancer ,  Rikke E. Humble

IPC分类号： C07D307/78 ,  C07D307/87 ,  C07D307/93

CPC分类号： C07D307/87 ,  C07C253/34

摘要： In the following, citalopram diol means 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)-benzonitrile, as free base and/or acid addition salt. The invention relates to a process for the preparation of racemic citalopram diol and/or R- or S-citalopram diol, comprising the separation of a non-racemic mixture of R- and S-citalopram diol with more than 50% of one of the enantiomers into a fraction being enriched with S- or R-citalopram diol and a fraction comprising RS-citalopram diol wherein the ratio of R-citalopram diol:S-citalopram diol is equal to 1:1 or closer to 1:1 than in the initial mixture. The method is characterized in that (i) RS-citalopram diol is precipitated from a solution of the initial non-racemic mixture, or R- or S-citalopram diol is dissolved into a solvent from the initial non-racemic mixture, leaving a residue of RS-citalopram diol, and in that (ii) the residue/precipitate formed is separated from the final solution phase, followed by optional steps of repetition, recrystallisation, purification, isolation and conversion between free base and salts. The invention also relates to a process for the preparation of RS-citalopram, S-citalopram or R-citalopram (all as free base and/or acid addition salt) comprising the method described above followed by ring closure.

摘要翻译： 在下文中，西酞普兰二醇是指作为游离碱和/或酸加成盐的4-（4-（二甲基氨基）-1-（4-氟苯基）-1-羟基丁基）-3-（羟甲基） - 苄腈。 本发明涉及一种制备外消旋西酞普兰二醇和/或R-或S-西酞普兰二醇的方法，包括将R-和S-西酞普兰二醇的非外消旋混合物与50％以上的 对映异构体转化成富含S-或R-西酞普兰二醇的级分和包含RS-西酞普兰二醇的级分，其中R-西酞普兰二醇：西西酞普兰二醇的比例等于1:1比或接近1比1 初始混合物。 该方法的特征在于（i）RS-西酞普兰二醇从初始非外消旋混合物的溶液中沉淀，或将R-或S-西酞普兰二醇从初始非外消旋混合物中溶解到溶剂中，留下残余物 的RS-西酞普兰二醇，并且（ii）所形成的残余物/沉淀物与最终溶液相分离，随后重复，重结晶，纯化，分离和转化游离碱和盐之间的任选步骤。 本发明还涉及一种制备RS-西酞普兰，西酞普兰或R-西酞普兰（均为游离碱和/或酸加成盐）的方法，包括上述方法，然后闭环。

公开(公告)号：US07834201B2

公开(公告)日：2010-11-16

申请号：US11425522

申请日：2006-06-21

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： C07D307/87

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

摘要翻译： 本发明涉及众所周知的抗抑郁药物依他普仑S-1- [3-（二甲基氨基）丙基] -1-（4-氟苯基）-1,3-二氢-5-异苯并呋喃甲腈的结晶碱，所述制剂为 碱，使用碱，草酸盐的纯化盐的制备方法，通过所述方法获得的盐和含有这些盐的制剂的方法，以及制备纯化的依他普仑游离碱或依他普仑的盐的方法， 例如草酸盐，使用氢溴酸盐，通过所述方法获得的盐和含有这些盐的制剂。 最后，本发明涉及硬度至少为22N，口服崩解时间小于120秒的可分散片剂，其包含吸附在水溶性填料上的活性药物成分，其中活性药物成分的熔点为 40-100℃的范围，以及制造这种可分散片剂的方法。

公开(公告)号：US20050137255A1

公开(公告)日：2005-06-23

申请号：US11025532

申请日：2004-12-29

申请人： Hans Petersen ,  Peter Ellegaard ,  Lawrence Martel ,  Robert Dancer

发明人： Hans Petersen ,  Peter Ellegaard ,  Lawrence Martel ,  Robert Dancer

IPC分类号： A61K31/343 ,  C07D307/87 ,  C07D307/78

CPC分类号： C07D307/87 ,  A61K31/343

摘要： The present invention provides crystalline escitalopram hydrobromide ((S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzo-furan carbonitrile hydrobromide), and a novel crystalline form of escitalopram hydrobromide referred to herein as Form I. Form I is stable, water soluble, and not hygroscopic at a relative humidity less than 70%.

摘要翻译： 本发明提供结晶的依他普仑氢溴酸盐（（S）-1- [3-（二甲基氨基）丙基] -1-（4-氟苯基）-1,3-二氢-5-异苯并呋喃腈氢溴酸盐） 本文称为形式I的依他普仑氢溴酸盐的形式。在相对湿度小于70％时，I型是稳定的，水溶性的，并且不吸湿。

公开(公告)号：US07371863B2

公开(公告)日：2008-05-13

申请号：US10570551

申请日：2004-09-01

申请人： Hans Petersen ,  Michael Bech Sommer ,  Robert Dancer

发明人： Hans Petersen ,  Michael Bech Sommer ,  Robert Dancer

IPC分类号： C07D471/02 ,  C07D491/02 ,  C07D498/02

CPC分类号： C07D498/04

摘要： The present invention relates to a new method of preparing gaboxadol (THIP), which is useful for treating sleep disorders. In particular a method of preparing THIP comprising reacting a compound of formula (8b) or a salt thereof with an acid, typically a mineral acid, to obtain THIP as an acid addition salt. The present invention also relates to several intermediates

摘要翻译： 本发明涉及一种制备加波沙朵（THIP）的新方法，其可用于治疗睡眠障碍。 特别是制备THIP的方法，包括使式（8b）的化合物或其盐与酸（通常为无机酸）反应，得到THIP作为酸加成盐。 本发明还涉及几种中间体

公开(公告)号：US07112686B2

公开(公告)日：2006-09-26

申请号：US10482000

申请日：2002-06-25

申请人： Rikke E. Humble ,  Troels V. Christensen ,  Michael H. Rock ,  Ole Nielsen ,  Hans Petersen ,  Robert Dancer

发明人： Rikke E. Humble ,  Troels V. Christensen ,  Michael H. Rock ,  Ole Nielsen ,  Hans Petersen ,  Robert Dancer

IPC分类号： C07D307/78 ,  C07D307/87 ,  C07D307/93

CPC分类号： C07D307/87

摘要： The invention relates to a process for the preparation of racemic citalopram free base or an acid addition salt thereof and/or R- or S-citalopram as the free base or an acid addition salt thereof by separation of a mixture of R- and S-citalopram with more than 50% of one of the enantiomers into a fraction consisting of racemic citalopram and/or a fraction of S-citalopram or R-citalopram characterized in that i) citalopram is precipitated from a solvent as the free base or as an acid addition salt thereof; ii) the precipitate formed is separated from the mother liquor; iia) if the precipitate is crystalline it is optionally recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iib) if the precipitate is not crystalline, steps i) and ii) are optionally repeated until a crystalline precipitate is obtained and the crystalline precipitate is recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iii) the mother liquor is optionally subjected to further purification and S-citalopram or R-citalopram is isolated from the mother liquor and optionally converted into an addition salt thereof.

摘要翻译： 本发明涉及一种通过分离R和S-的混合物来制备外消旋西酞普兰游离碱或其酸加成盐和/或R-或S-西酞普兰作为游离碱或其酸加成盐的方法， 西酞普兰与超过50％的一种对映异构体组成由外消旋西酞普兰和/或S-西酞普兰或R-西酞普兰的部分组成的部分，其特征在于i）西酞普兰作为游离碱或作为酸从溶剂中沉淀出来 其加成盐; ii）形成的沉淀物与母液分离; 如果沉淀物是结晶的，则任选地重结晶一次或多次以形成外消旋西酞普兰，然后任选地转化成其酸加成盐; iib）如果沉淀物不结晶，则任选地重复步骤i）和ii），直到获得结晶沉淀物，并将结晶沉淀物重结晶一次或多次以形成外消旋西酞普兰，然后任选地转化为其酸加成盐; iii）任选地将母液进一步纯化，并从母液中分离S-西酞普兰或R-西酞普兰，并任选地转化成其加成盐。