公开(公告)号：US06753409B1

公开(公告)日：2004-06-22

申请号：US09639634

申请日：2000-08-15

申请人： Zofia J. Chrzan ,  James J. Mencel ,  David Toledo-Velasquez ,  Vincent Windisch ,  Rick G. Woodward ,  Diane C. Salazar ,  Narasimha M. Vemuri ,  Anthony J. Gardetto ,  Matthew R. Powers ,  Gregory G. Kubiak ,  Robert C. Liu ,  Benoit J. Vanasse ,  James P. Sherbine ,  Walter Rodriguez ,  Adam W. Sledeski

发明人： Zofia J. Chrzan ,  James J. Mencel ,  David Toledo-Velasquez ,  Vincent Windisch ,  Rick G. Woodward ,  Diane C. Salazar ,  Narasimha M. Vemuri ,  Anthony J. Gardetto ,  Matthew R. Powers ,  Gregory G. Kubiak ,  Robert C. Liu ,  Benoit J. Vanasse ,  James P. Sherbine ,  Walter Rodriguez ,  Adam W. Sledeski

IPC分类号： C07K508

CPC分类号： C07D211/34 ,  C07K5/021 ,  C07K5/0806

摘要： The invention is directed to a non-hygroscopic stable crystalline form of the antithrombotic compound N-[N-[N-(4-piperdin-4-yl)butanoyl)-N-ethylglycyl]-(L)-aspartyl]-(L)-&bgr;-cyclohexyl-alanine amide, to processes for preparing said stable crystalline form, to a pharmaceutical composition thereof, and intermediates thereof, and the invention is directed also to processes for preparing a compound of the formula wherein: A, B, Z, E1, E2, G, R, m, n, and p are as defined herein.

摘要翻译： 本发明涉及抗血栓形成的化合物N- [N- [N-（4-哌啶-4-基）丁酰基）-N-乙基甘氨酰] - （L） - 天门冬酰基] - （L ） - 环己基 - 丙氨酸酰胺，制备所述稳定结晶形式的方法，其制备方法及其中间体，本发明还涉及制备糠醛的化合物的方法：A，B，Z， E 1，E 2，G，R，m，n和p如本文所定义。

公开(公告)号：US6153588A

公开(公告)日：2000-11-28

申请号：US251030

申请日：1999-02-18

申请人： Zofia J. Chrzan ,  James J. Mencel ,  David Toledo-Velasquez ,  Vincent Windisch ,  Rick G. Woodward ,  Diane C. Salazar, deceased ,  Narasimha M. Vemuri ,  Anthony J. Gardetto ,  Matthew R. Powers ,  Gregory G. Kubiak ,  Robert C. Liu ,  Benoit J. Vanasse ,  James P. Sherbine ,  Walter Rodriguez ,  Adam W. Sledeski

发明人： Zofia J. Chrzan ,  James J. Mencel ,  David Toledo-Velasquez ,  Vincent Windisch ,  Rick G. Woodward ,  Diane C. Salazar, deceased ,  Narasimha M. Vemuri ,  Anthony J. Gardetto ,  Matthew R. Powers ,  Gregory G. Kubiak ,  Robert C. Liu ,  Benoit J. Vanasse ,  James P. Sherbine ,  Walter Rodriguez ,  Adam W. Sledeski

IPC分类号： C07D211/70 ,  A61K38/00 ,  A61P7/02 ,  A61P9/10 ,  C07D211/34 ,  C07K5/02 ,  C07K5/062 ,  C07K5/083 ,  A61K38/06 ,  C07K5/00

CPC分类号： C07K5/021 ,  C07D211/34 ,  C07K5/0806 ,  Y02P20/55

摘要： The invention is directed to a non-hygroscopic stable crystalline form of the antithrombotic compound N-[N-[N-(4-piperdin-4-yl)butanoyl)-N-ethylglycyl]-(L)-aspartyl]-(L)-.beta.-cyclohexyl-alanine amide, to processes for preparing said stable crystalline form, to a pharmaceutical composition thereof, and intermediates thereof, and the invention is directed also to processes for preparing a compound of the formula ##STR1## wherein: A, B, Z, E.sup.1, E.sup.2, G, R, m, n, and p are as defined herein.

摘要翻译： 本发明涉及抗血栓形成的化合物N- [N- [N-（4-哌啶-4-基）丁酰基）-N-乙基甘氨酰] - （L） - 天门冬酰基] - （L ）-β-环己基 - 丙氨酸酰胺，制备所述稳定结晶形式的方法，其制备方法及其中间体，本发明还涉及制备下式化合物的方法：其中：A，B，Z ，E1，E2，G，R，m，n和p如本文所定义。

公开(公告)号：US06641063B2

公开(公告)日：2003-11-04

申请号：US09873161

申请日：2001-06-01

申请人： Narasimha M. Vemuri ,  Andrew B. Brown ,  Jean-Rene Authelin ,  Patrik Hosek

发明人： Narasimha M. Vemuri ,  Andrew B. Brown ,  Jean-Rene Authelin ,  Patrik Hosek

IPC分类号： B02C1906

CPC分类号： A61K9/0075 ,  A61K9/14 ,  B02C19/06

摘要： The invention is an improved method of generating fine medicament powders suitable for inhalation. A fluid energy mill is used with conventional milling fluids such as air or nitrogen. The milling fluid is treated to have a controlled relative humidity of between 30% and 70%. This produces a fine medicament powder with a median particle size below 10 micrometer but with little or no amorphous content generated during milling. Scale formation in the mill chamber is also greatly reduced.