公开(公告)号：US07410987B2

公开(公告)日：2008-08-12

申请号：US11434028

申请日：2006-05-15

申请人： Maki Tokai ,  Takahiro Honda ,  Masashi Niwa ,  Yaeko Osumi ,  Ken-ichi Fujimura ,  Shin-ichi Kohno

发明人： Maki Tokai ,  Takahiro Honda ,  Masashi Niwa ,  Yaeko Osumi ,  Ken-ichi Fujimura ,  Shin-ichi Kohno

IPC分类号： A61K31/428 ,  A61P29/00

CPC分类号： C07D417/12 ,  A61K31/428 ,  C07D277/66

摘要： A method of treating pain or pruritis comprising administering to a patient in need thereof a pharmaceutically effective amount of a κ opioid receptor agonist of the formula wherein R is an alkyl having an amino group as a substituent; and R1 is acyl.

摘要翻译： 一种治疗疼痛或瘙痒症的方法，包括向有需要的患者施用药学有效量的下式的κ阿片受体激动剂其中R是具有氨基作为取代基的烷基; R 1是酰基。

公开(公告)号：US20060205796A1

公开(公告)日：2006-09-14

申请号：US11434028

申请日：2006-05-15

申请人： Maki Tokai ,  Takahiro Honda ,  Masashi Niwa ,  Yaeko Osumi ,  Ken-ichi Fujimura ,  Shin-ichi kohno

发明人： Maki Tokai ,  Takahiro Honda ,  Masashi Niwa ,  Yaeko Osumi ,  Ken-ichi Fujimura ,  Shin-ichi kohno

IPC分类号： A61K31/428

CPC分类号： C07D417/12 ,  A61K31/428 ,  C07D277/66

摘要： A method of treating pain or pruritis comprising administering to a patient in need thereof a pharmaceutically effective amount of a κ opioid receptor agonist of the formula wherein R is an alkyl having an amino group as a substituent; and R1 is acyl.

摘要翻译： 一种治疗疼痛或瘙痒症的方法，包括向有需要的患者施用药学有效量的下式的κ阿片受体激动剂其中R是具有氨基作为取代基的烷基; R 1是酰基。

公开(公告)号：US07112598B2

公开(公告)日：2006-09-26

申请号：US10509549

申请日：2003-03-28

申请人： Maki Tokai ,  Takahiro Honda ,  Masashi Niwa ,  Yaeko Osumi ,  Ken-ichi Fujimura ,  Shin-ichi Kohno

发明人： Maki Tokai ,  Takahiro Honda ,  Masashi Niwa ,  Yaeko Osumi ,  Ken-ichi Fujimura ,  Shin-ichi Kohno

IPC分类号： C07D277/66 ,  C07D417/12 ,  A61K31/428 ,  A61P29/00 ,  A61P25/04

CPC分类号： C07D417/12 ,  A61K31/428 ,  C07D277/66

摘要： A compound or a salt thereof having the following formula wherein R1 is acyl, R2 is hydrogen, halogen, unsubstituted alkyl or alkyl substituted by halogen; R3 is halogen or alkoxy; R4 is cycloalkyl, unsubstituted alkyl or alkyl substituted by cycloalkyl, aryl or hydroxyl or an ester thereof or alkoxy; R5 is hydroxyl or an ester thereof, alkoxy or alkoxyalkyl; or R4 and R5 are bonded with each other to form a pyrrolidine ring substituted by hydroxyl or an ester thereof, alkoxy or alkoxyalkyl; R6 is hydroxyl or an ester thereof, alkoxy, alkoxyalkoxy, alkoxyalkoxyalkoxy, mercapto or alkylthio; and A1 and A2, are the same or different, and are alkylene, provided that (i) when R4 and R5 are bonded to each other to form the pyrrolidine ring substituted by hydroxyl or an ester thereof, R2 is halogen; (ii) when R4 and R5 are bonded to each other to form the pyrrolidine ring substituted by alkoxyalkyl, R2 is hydrogen; (iii) when R6 is hydroxyl or an ester thereof, R4 is isopropyl.

摘要翻译： 具有下式的化合物或其盐，其中R 1是酰基，R 2是氢，卤素，未取代的烷基或被卤素取代的烷基; R 3是卤素或烷氧基; R 4是环烷基，未取代的烷基或被环烷基，芳基或羟基或其酯或烷氧基取代的烷基; R 5是羟基或其酯，烷氧基或烷氧基烷基; 或R 4和R 5彼此键合以形成被羟基或其酯取代的吡咯烷环，烷氧基或烷氧基烷基; R 6是羟基或其酯，烷氧基，烷氧基烷氧基，烷氧基烷氧基烷氧基，巯基或烷硫基; 和A 1和A 2各自相同或不同，并且是亚烷基，条件是（i）当R 4和R 0 > 5个彼此键合以形成被羟基或其酯取代的吡咯烷环，R 2是卤素; （ii）当R 4和R 5彼此键合以形成被烷氧基烷基取代的吡咯烷环时，R 2是氢; （iii）当R 6为羟基或其酯时，R 4为异丙基。

公开(公告)号：US09029398B2

公开(公告)日：2015-05-12

申请号：US13384590

申请日：2010-07-16

申请人： Masashi Niwa ,  Hiroshi Deguchi

发明人： Masashi Niwa ,  Hiroshi Deguchi

IPC分类号： C07D213/82 ,  A61K31/455 ,  C07D401/12

CPC分类号： C07D213/82 ,  A61K31/455 ,  C07B2200/13 ,  C07C303/32 ,  C07C309/29 ,  C07D401/12

摘要： In the course of developing 2-[[[2-[(hydroxyacetyl)amino]-4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide (compound A), there are the multiple problems: 1) compound A or its salt is difficult to be recrystallized, the storage stability largely differs depending on the kind of the salt, and it is very difficult to obtain a salt of compound A having excellent storage stability; 2) in a crystallization process of compound A, it is very difficult to control a crystal polymorph, and 3) compound A (free body) causes mineral deposition in the stomach when it is orally administered repeatedly. For solving these problems, we made examination focusing on the kind of the salt and, as a result, found that 1) benzenesulfonate of compound A does not decompose by light, humidity and other factors in a 1-week preliminary stability test (severe test), and has no problem in its storage stability, 2) a method of selectively producing two kinds of crystal forms of benzenesulfonate of compound A, and that 3) no mineral deposition in the stomach is observed even after a 4-week repeated oral administration.

摘要翻译： 在开发2 - [[[2 - [（羟基乙酰基）氨基] -4-吡啶基]甲基]硫基] -N- [4-（三氟甲氧基）苯基] -3-吡啶甲酰胺（化合物A）的过程中， 多个问题：1）化合物A或其盐难以重结晶，储存稳定性根据盐的种类而有很大差异，难以获得具有优异储存稳定性的化合物A的盐; 2）在化合物A的结晶过程中，控制晶体多晶型是非常困难的，3）化合物A（游离体）在重复口服给药时会引起胃中的矿物质沉积。 为了解决这些问题，我们考察了盐的种类，结果发现化合物A的1）苯磺酸盐在1周的初步稳定性试验（严重试验）中不会被光，湿度等因素分解 ），并且其储存稳定性没有问题; 2）选择性地生成化合物A的苯磺酸盐的两种晶体形式的方法，以及3）即使在4周的重复口服给药后也没有观察到在胃中的矿物质沉积 。

公开(公告)号：US5450870A

公开(公告)日：1995-09-19

申请号：US162187

申请日：1993-12-16

申请人： Makoto Suga ,  Masashi Niwa ,  Fumio Kojima ,  Nobumasa Ishida ,  Koji Kondo

发明人： Makoto Suga ,  Masashi Niwa ,  Fumio Kojima ,  Nobumasa Ishida ,  Koji Kondo

IPC分类号： C23C18/16 ,  G05D21/02 ,  G05D11/08

CPC分类号： C23C18/1683 ,  C23C18/1628 ,  G05D21/02 ,  Y10T137/0329 ,  Y10T137/2509

摘要： According to the present invention, the changing rate of the predetermined component concentration is determined, based on the difference between the predetermined component concentration in a chemical treating solution (a plating solution) which is analyzed this time and the predetermined component concentration analyzed last time, both measured by an analytical means, and the difference of each sampling time for analysis of each component concentration by the analytical means (140). Subsequently, the correction amount for the analyzed result of this time based on the changing rate obtained above and the elapsed time from the sampling point of time of the plating solution of this time for analysis of the plating solution by the analytical means to the current point of time (150), and then the analyzed result is corrected based on the resulting correction amount to compute or calculate the current concentration (160). As the result, the current concentration can be detected accurately regardless of the analyzing time of the plating solution by the analytical means.

摘要翻译： PCT No.PCT / JP93 / 00486 Sec。 371日期：1993年12月16日 102（e）日期1993年12月16日PCT提交1993年4月16日PCT公布。 公开号WO93 / 21359 日期为1993年10月28日。根据本发明，基于本次分析的化学处理溶液（电镀液）中的规定成分浓度与本发明的分析浓度之间的差异，确定预定成分浓度的变化率 通过分析手段测量的上次分析的预定组分浓度和通过分析装置（140）分析每种组分浓度的每个采样时间的差异。 随后，根据上述获得的变化率，将该时刻的分析结果的校正量和从该分析手段分析电镀液的时刻的电镀溶液的取样点到当前点的经过时间 的时间（150），然后基于所得到的校正量来校正分析结果，以计算或计算当前浓度（160）。 结果，可以准确地检测电流浓度，而不管分析装置的电镀溶液的分析时间如何。

公开(公告)号：US20120116088A1

公开(公告)日：2012-05-10

申请号：US13384590

申请日：2010-07-16

申请人： Masashi Niwa ,  Hiroshi Deguchi

发明人： Masashi Niwa ,  Hiroshi Deguchi

IPC分类号： C07D401/12

CPC分类号： C07D213/82 ,  A61K31/455 ,  C07B2200/13 ,  C07C303/32 ,  C07C309/29 ,  C07D401/12

摘要： In the course of developing 2-[[[2-[(hydroxyacetyl)amino]-4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide (compound A), there are the multiple problems: 1) compound A or its salt is difficult to be recrystallized, the storage stability largely differs depending on the kind of the salt, and it is very difficult to obtain a salt of compound A having excellent storage stability; 2) in a crystallization process of compound A, it is very difficult to control a crystal polymorph, and 3) compound A (free body) causes mineral deposition in the stomach when it is orally administered repeatedly. For solving these problems, we made examination focusing on the kind of the salt and, as a result, found that 1) benzenesulfonate of compound A does not decompose by light, humidity and other factors in a 1-week preliminary stability test (severe test), and has no problem in its storage stability, 2) a method of selectively producing two kinds of crystal forms of benzenesulfonate of compound A, and that 3) no mineral deposition in the stomach is observed even after a 4-week repeated oral administration.

摘要翻译： 在开发2 - [[[2 - [（羟基乙酰基）氨基] -4-吡啶基]甲基]硫基] -N- [4-（三氟甲氧基）苯基] -3-吡啶甲酰胺（化合物A）的过程中， 多个问题：1）化合物A或其盐难以重结晶，储存稳定性根据盐的种类而有很大差异，难以获得具有优异储存稳定性的化合物A的盐; 2）在化合物A的结晶过程中，控制晶体多晶型是非常困难的，3）化合物A（游离体）在重复口服给药时会引起胃中的矿物质沉积。 为了解决这些问题，我们考察了盐的种类，结果发现化合物A的1）苯磺酸盐在1周的初步稳定性试验（严重试验）中不会被光，湿度等因素分解 ），并且其储存稳定性没有问题; 2）选择性地生成化合物A的苯磺酸盐的两种晶体形式的方法，以及3）即使在4周的重复口服给药后也没有观察到在胃中的矿物质沉积 。

公开(公告)号：US07912821B2

公开(公告)日：2011-03-22

申请号：US12391041

申请日：2009-02-23

申请人： Hiroaki Ishimoto ,  Jo Ajisawa ,  Naohiro Itou ,  Masashi Niwa

发明人： Hiroaki Ishimoto ,  Jo Ajisawa ,  Naohiro Itou ,  Masashi Niwa

IPC分类号： G06F17/00

CPC分类号： G06F17/30362

摘要： A data management method includes a reference activation step, after generating a first time-series data for causing chronological relationship to be identifiable in a memory device at activation of a reference operation to a first record in a database, of referring to the first record; an update step, in response to an update request for the first record, of generating a second record corresponding to the first record in the database and updating the second record; a commit step of generating a second time-series data in the memory device at a commit operation for the updating; a reference termination step of deleting the first time-series data at completion of the reference operation; and a deletion step, if the first time-series data generated earlier than the second time-series data is not present as a result of the commit step or the reference termination step, of deleting the first record.

摘要翻译： 数据管理方法包括参考激活步骤，在参照第一记录产生第一时间序列数据之后，在激活对数据库中的第一记录的参考操作时，使存储器装置中的时间关系可识别; 更新步骤，响应于对所述第一记录的更新请求，生成与所述数据库中的所述第一记录相对应的第二记录，并更新所述第二记录; 提交步骤，用于在所述更新的提交操作中在所述存储器设备中生成第二时间序列数据; 参考终止步骤，在完成参考操作时删除第一时间序列数据; 以及删除步骤，如果作为提交步骤或参考终止步骤的结果，不早于第二时间序列数据生成的第一时间序列数据，则删除第一记录。

公开(公告)号：US20090292706A1

公开(公告)日：2009-11-26

申请号：US12391041

申请日：2009-02-23

申请人： Hiroaki Ishimoto ,  Jo Ajisawa ,  Naohiro Itou ,  Masashi Niwa

发明人： Hiroaki Ishimoto ,  Jo Ajisawa ,  Naohiro Itou ,  Masashi Niwa

IPC分类号： G06F17/30

CPC分类号： G06F17/30362

摘要： A data management method includes a reference activation step, after generating a first time-series data for causing chronological relationship to be identifiable in a memory device at activation of a reference operation to a first record in a database, of referring to the first record; an update step, in response to an update request for the first record, of generating a second record corresponding to the first record in the database and updating the second record; a commit step of generating a second time-series data in the memory device at a commit operation for the updating; a reference termination step of deleting the first time-series data at completion of the reference operation; and a deletion step, if the first time-series data generated earlier than the second time-series data is not present as a result of the commit step or the reference termination step, of deleting the first record.

摘要翻译： 数据管理方法包括参考激活步骤，在参照第一记录产生第一时间序列数据之后，在激活对数据库中的第一记录的参考操作时，使存储器装置中的时间关系可识别; 更新步骤，响应于对所述第一记录的更新请求，生成与所述数据库中的所述第一记录相对应的第二记录，并更新所述第二记录; 提交步骤，用于在所述更新的提交操作中在所述存储器设备中生成第二时间序列数据; 参考终止步骤，在完成参考操作时删除第一时间序列数据; 以及删除步骤，如果作为提交步骤或参考终止步骤的结果，不早于第二时间序列数据生成的第一时间序列数据，则删除第一记录。