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：US07723533B2

公开(公告)日：2010-05-25

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.

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：US20080161388A1

公开(公告)日：2008-07-03

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： A61K31/343 ,  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.

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：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：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：US08076320B2

公开(公告)日：2011-12-13

申请号：US10597977

申请日：2005-02-24

申请人： Michael Harold Rock ,  Heidi Lopez De Diego ,  Kim Lasse Christensen ,  Ole Nielsen ,  Anders Buur ,  Mark Howells

发明人： Michael Harold Rock ,  Heidi Lopez De Diego ,  Kim Lasse Christensen ,  Ole Nielsen ,  Anders Buur ,  Mark Howells

IPC分类号： A61P25/16 ,  A61K31/7056 ,  C07H19/23

CPC分类号： C07H19/23 ,  C07D491/22

摘要： Described are crystalline forms of the pharmaceutical compound “[9S-(9α,10β,12α)]-5,16-Bis[(ethylthio)methyl]-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9, 12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester”, as well as methods for their use and preparation.

摘要翻译： 描述了药物化合物“[9S-（9α，10α，12α）] -5,16-双[（乙硫基）甲基] -2,3,9,10,11,12-六氢-10- -4-羟基-9-甲基-1-氧代-9,12-环氧基-1H-二吲哚并[1,2,3-fg：3'，2'，1'-k]吡咯并[3,4-i] 6]苯并二氮辛-10-羧酸甲酯“，以及它们的使用和制备方法。

公开(公告)号：US20110124629A1

公开(公告)日：2011-05-26

申请号：US12983558

申请日：2011-01-03

申请人： Michael Harold Rock ,  Heidi Lopez De Diego ,  Kim Lasse Christensen ,  Ole Nielsen ,  Anders Buur ,  Mark Howells

发明人： Michael Harold Rock ,  Heidi Lopez De Diego ,  Kim Lasse Christensen ,  Ole Nielsen ,  Anders Buur ,  Mark Howells

IPC分类号： A61K31/553 ,  C07D519/00 ,  A61P25/28 ,  A61P25/16

CPC分类号： C07H19/23 ,  C07D491/22

摘要： Described are crystalline forms of the pharmaceutical compound “[9S-(9α,10β,12α)]-5,16-Bis[(ethylthio)methyl]-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3 -fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester”, as well as methods for their use and preparation.

摘要翻译： 描述了药物化合物“[9S-（9α，10α，12α）] -5,16-双[（乙硫基）甲基] -2,3,9,10,11,12-六氢-10- 羟基-9-甲基-1-氧代-9,12-环氧基-1H-二吲哚并[1,2,3-f]，3'，2'，1'-kl]吡咯并[3,4-i] 6]苯并二氮辛-10-羧酸甲酯“，以及它们的使用和制备方法。

公开(公告)号：US08729065B2

公开(公告)日：2014-05-20

申请号：US12983558

申请日：2011-01-03

申请人： Michael Harold Rock ,  Heidi Lopez De Diego ,  Kim Lasse Christensen ,  Ole Nielsen ,  Anders Buur ,  Mark Howells

发明人： Michael Harold Rock ,  Heidi Lopez De Diego ,  Kim Lasse Christensen ,  Ole Nielsen ,  Anders Buur ,  Mark Howells

IPC分类号： A61P25/16 ,  A61K31/553 ,  C07D498/12

CPC分类号： C07H19/23 ,  C07D491/22

摘要： Described are crystalline forms of the pharmaceutical compound “[9S-(9α,10β,12α)]-5,16-Bis[(ethylthio)methyl]-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester”, as well as methods for their use and preparation.

摘要翻译： 描述了药物化合物“[9S-（9α，10α，12α）] -5,16-双[（乙硫基）甲基] -2,3,9,10,11,12-六氢-10- 羟基-9-甲基-1-氧代-9,12-环氧基-1H-二吲哚并[1,2,3-fg：3'，2'，1'-k]吡咯并[3,4-i] 6]苯并二氮辛-10-羧酸甲酯“，以及它们的使用和制备方法。

公开(公告)号：US07271273B2

公开(公告)日：2007-09-18

申请号：US11285922

申请日：2005-11-23

申请人： Hans Petersen ,  Michael Harold Rock

发明人： Hans Petersen ,  Michael Harold Rock

IPC分类号： C07D307/54

CPC分类号： C07D307/88

摘要： The invention provides a new and improved method for the preparation of 5-cyano-phtalid, which is a key intermediate in the preparation of the antidepressant compound citalopram.

摘要翻译： 本发明提供了一种新的改进的制备5-氰基 - 邻苯二甲酸的方法，该方法是制备抗抑郁化合物西酞普兰的关键中间体。