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1. 发明公开

EP2170831A1 BENZAZEPINE DERIVATIVES USEFUL AS VASOPRESSIN ANTAGONISTS 有权
标题翻译：作为精氨酸加压素拮抗剂合适的苯并吖庚因衍生物
公开(公告)号：EP2170831A1
公开(公告)日：2010-04-07
申请号：EP08765871.2
申请日：2008-06-26
申请人： Otsuka Pharmaceutical Co., Ltd.
发明人： KONDO, Kazumi , MENJO, Yasuhiro , TOMOYASU, Takahiro , MIYAMURA, Shin , TOMOHIRA, Yuso , MATSUDA, Takakuni , YAMADA, Keigo , KATO, Yusuke
IPC分类号： C07D223/16 , C07D405/12 , A61K31/55 , A61P7/00 , A61P9/00
CPC分类号： C07D223/16 , C07D405/12 , C07F9/5535 , Y02P20/55
摘要： The present invention provides a benzazepine compound that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects. The benzazepine compound of the present invention is represented by general formula (1) wherein R 1 represents a -CO-(CH 2 ) n -COR 2 group (wherein n is an integer of 1 to 4, and R 2 is (2-1) a hydroxy group; (2-2) a lower alkoxy group optionally substituted with a hydroxy group, a lower alkanoyl group, a lower alkanoyloxy group, a lower alkoxycarbonyloxy group, a cycloalkyloxycarbonyloxy group, or 5-methyl-2-oxo-1,3-dioxol-4-yl; or (2-3) an amino group optionally substituted with a hydroxy-lower alkyl group), or the like.

2. 发明授权

EP1300160B1 METHOD OF STABILIZING PREPARATION 有权
标题翻译：的稳定化方法的准备
公开(公告)号：EP1300160B1
公开(公告)日：2014-03-12
申请号：EP01932213.0
申请日：2001-05-23
申请人： OTSUKA PHARMACEUTICAL CO., LTD.
发明人： TOMOHIRA, Yuso , MUKAI, Tadashi , KASHIMOTO, Minoru , NAGASAWA, Masakazu , ICHIBA, Tetsuroh 59-15, Aza Sumiyoshikaitaku , KURIBAYASHI, Daisuke , OKA, Yoshikazu , TOGUCHI, Hajime
IPC分类号： A61K31/4709 , A61K47/02 , A61K47/12 , A61K47/20 , A61K9/20
CPC分类号： A61K9/2054 , A61K9/2013 , A61K47/02 , A61K47/20

3. 发明公开

EP1162973A1 CILOSTAZOL PREPARATION 有权
标题翻译：含西洛他唑的制备
公开(公告)号：EP1162973A1
公开(公告)日：2001-12-19
申请号：EP00909776.7
申请日：2000-03-21
申请人： OTSUKA PHARMACEUTICAL CO., LTD.
发明人： MUKAI, Tadashi , TOMOHIRA, Yuso , TODA, Masafumi , YAMADA, Keigo , OKA, Yoshikazu
IPC分类号： A61K31/47 , A61K9/14
CPC分类号： A61K9/145 , A61K9/146 , A61K9/1617 , A61K9/1652 , A61K9/2081 , A61K9/5042 , A61K9/5084 , A61K31/4709 , Y10S514/951 , Y10S514/952 , Y10S514/96 , Y10S514/961 , Y10S514/962 , Y10S514/963 , Y10S514/964
摘要： Provided is a cilostazol preparation which comprises incorporating a fine powder of cilostazol into a dispersing and/or solubilizing agent thereby to enhance the dispersibility and/or solubility. Further, provided is a process for improving absorbability of a slightly soluble drug such as cilostazol even at the lower portion of the digestive tract, wherein said drug is hard to be absorbed at the lower portion of the digestive tract when a conventional method is used. According to the present invention, cilostazol is absorbed enough even at the lower portion of the digestive tract to have an effect as thrombolytic drug, cerebral circulation improving drug or the like.

4. 发明公开

EP1970040A1 METHOD OF PRODUCING DRUG-CONTAINING WAX MATRIX PARTICLES, EXTRUDER TO BE USED IN THE METHOD AND SUSTAINED-RELEASE PREPARATION CONTAINING CILOSTAZOL 审中-公开
标题翻译：用于生产药物含有蜡的基质颗粒在程序中使用，SANTANDER挤出西洛他唑含缓释制剂
公开(公告)号：EP1970040A1
公开(公告)日：2008-09-17
申请号：EP06835067.7
申请日：2006-12-21
申请人： OTSUKA PHARMACEUTICAL CO., LTD.
发明人： TOMOHIRA, Yuso , YAMAGUCHI, Yasuo
IPC分类号： A61J3/06 , A61K9/14 , A61K31/4709 , A61K31/522 , A61K47/12 , A61K47/14 , A61K47/44 , B01J2/04
CPC分类号： A61J3/06 , A61J2200/20 , A61K9/148 , A61K31/4709 , A61K31/522 , B01J2/20
摘要： The present invention aims to provide a method for producing, by a simple method, drug-containing wax matrix granules, particularly drug-containing wax matrix granules having an average particle diameter of 1 mm or lower, while avoiding liquid blockage due to the recrystallization of a molten drug during the period from a melting step to a spray step.
Drug-containing wax matrix granules having at least one wax and at least one drug are produced by the following steps (i) and (ii): (i) supplying the at least one drug and the at least one wax to an extruder in which the temperature of a barrel and the temperature of a die are adjusted to be higher than the melting point of the at least one wax; and (ii) while melting and kneading the at least one drug and the at least one wax in the extruder to give a molten kneaded drug and wax, spraying the molten kneaded drug and wax into an atmosphere having a temperature lower than the melting point of the wax from a spray nozzle directly mounted onto a die provided at a top end of the barrel of the extruder, thereby forming the mixture into granules.
摘要翻译：本发明的目的是提供生产的方法，通过简单的方法，含有药物的蜡基质颗粒，具有在1毫米或更低的平均粒径，同时避免液体淤塞由于再结晶尤其含有药物的蜡基质颗粒在从熔化步骤到喷射步骤期间熔化的药物。具有至少一种蜡和至少一种药物含有药物的蜡基质颗粒通过以下的步骤（i）和（Ⅱ）：（i）提供至少一种药物并在其中挤出机中的至少一种蜡，以筒和所述的温度的温度调整为比所述至少一种蜡的熔点高; 和（ii）同时熔融混炼的至少一种药物，并在挤出机中的至少一种蜡，得到熔融混炼物的药物和蜡，喷涂的熔融混炼药物和蜡进入到大气中具有温度比熔点低从喷嘴的蜡直接安装在设置在挤出机的料筒的顶部端部，从而使该混合物形成颗粒。

5. 发明公开

EP1300160A1 METHOD OF STABILIZING PREPARATION 有权
标题翻译：方法ZUR STABILISIERUNG EINER ZUBEREITUNG
公开(公告)号：EP1300160A1
公开(公告)日：2003-04-09
申请号：EP01932213.0
申请日：2001-05-23
申请人： OTSUKA PHARMACEUTICAL CO., LTD.
发明人： TOMOHIRA, Yuso , MUKAI, Tadashi , KASHIMOTO, Minoru , NAGASAWA, Masakazu , ICHIBA, Tetsuroh , KURIBAYASHI, Daisuke , OKA, Yoshikazu , TOGUCHI, Hajime
IPC分类号： A61K47/20 , A61K47/02 , A61K47/12 , A61K47/24
CPC分类号： A61K9/2054 , A61K9/2013 , A61K47/02 , A61K47/20
摘要： Disclosed is a method for stabilizing a solid pharmaceutical preparation containing a pharmacological substance and sodium lauryl sulfate, the method comprising incorporating into the preparation at least one member selected from the group consisting of neutral salts, basic salts and basic substances. The preparation containing sodium lauryl sulfate prepared by the method of the invention has superior performance, including high storage stability, suppression of discoloration and deterioration, and prevention of change in its properties, such as the dissolution rate of pharmacological substance from the preparation.
摘要翻译：公开了一种稳定含有药理学物质和十二烷基硫酸钠的固体药物制剂的方法，该方法包括将至少一种选自中性盐，碱性盐和碱性物质的成分掺入制剂中。通过本发明方法制备的含有十二烷基硫酸钠的制剂具有优异的性能，包括高储存稳定性，抑制变色和变质，以及防止其制备物质的药理学溶解速度等性质的改变。

6. 发明授权

EP1484056B1 SUSTAINED RELEASE PREPARATIONS AND PROCESS FOR PRODUCING THE SAME 有权
标题翻译：它们的制备持续释放和方法筹备工作
公开(公告)号：EP1484056B1
公开(公告)日：2013-08-14
申请号：EP03742668.1
申请日：2003-02-20
申请人： OTSUKA PHARMACEUTICAL CO., LTD.
发明人： TOMOHIRA, Yuso
IPC分类号： A61K9/50 , A61K47/04 , A61K47/12
CPC分类号： A61K9/5015 , A61K9/1617 , A61K9/501

7. 发明公开

EP1398040A1 MEDICINAL COMPOSITION 审中-公开
标题翻译： MEDIZINISCHE ZUSAMMENSETZUNG
公开(公告)号：EP1398040A1
公开(公告)日：2004-03-17
申请号：EP02728121.1
申请日：2002-05-23
申请人： OTSUKA PHARMACEUTICAL CO., LTD.
发明人： TOMOHIRA, Yuso
IPC分类号： A61K47/32 , A61K9/22 , A61K9/52 , A61K31/522 , A61K47/14 , A61K47/38 , A61P11/06
CPC分类号： A61K31/496 , A61K9/1617 , A61K9/1635 , A61K9/1652 , A61K31/4704 , A61K31/4709 , A61K31/522
摘要： The present invention provides a medicinal composition that exhibits excellent storage stability and, even over long-term storage, little change in the release rate of the pharmacologically active substance contained therein. The medicinal composition of the invention prepared by dissolving or dispersing a pharmacologically active substance and a pH-independent water-insoluble polymer in a molten low-melting substance, and which can be prepared by spraying a liquid substance, obtained by dissolving or dispersing the pharmacologically active substance in a molten mixture comprising the low-melting substance and the pH-independent water-insoluble polymer, and then cooling the liquid substance.
摘要翻译：通过将活性物质和与pH无关的水不溶性聚合物溶解或分散在熔融的低熔点物质中来制备药物组合物。

8. 发明授权

EP2170831B1 Benzazepine derivatives useful as vasopressin antagonists 有权
标题翻译：作为精氨酸加压素拮抗剂合适的苯并吖庚因衍生物
公开(公告)号：EP2170831B1
公开(公告)日：2012-02-15
申请号：EP08765871.2
申请日：2008-06-26
申请人： Otsuka Pharmaceutical Co., Ltd.
发明人： KONDO, Kazumi , MENJO, Yasuhiro , TOMOYASU, Takahiro , MIYAMURA, Shin , TOMOHIRA, Yuso , MATSUDA, Takakuni , YAMADA, Keigo , KATO, Yusuke
IPC分类号： C07D223/16 , C07D405/12 , A61K31/55 , A61P7/00 , A61P9/00
CPC分类号： C07D223/16 , C07D405/12 , C07F9/5535 , Y02P20/55
摘要： The present invention provides a benzazepine compound that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects. The benzazepine compound of the present invention is represented by general formula (1) wherein R 1 represents a -CO-(CH 2 ) n -COR 2 group (wherein n is an integer of 1 to 4, and R 2 is (2-1) a hydroxy group; (2-2) a lower alkoxy group optionally substituted with a hydroxy group, a lower alkanoyl group, a lower alkanoyloxy group, a lower alkoxycarbonyloxy group, a cycloalkyloxycarbonyloxy group, or 5-methyl-2-oxo-1,3-dioxol-4-yl; or (2-3) an amino group optionally substituted with a hydroxy-lower alkyl group), or the like.

9. 发明授权

EP1162973B1 CILOSTAZOL PREPARATION 有权
标题翻译：含西洛他唑的制备
公开(公告)号：EP1162973B1
公开(公告)日：2005-05-25
申请号：EP00909776.7
申请日：2000-03-21
申请人： OTSUKA PHARMACEUTICAL CO., LTD.
发明人： MUKAI, Tadashi , TOMOHIRA, Yuso , TODA, Masafumi , YAMADA, Keigo , OKA, Yoshikazu
IPC分类号： A61K31/47 , A61K9/14
CPC分类号： A61K9/145 , A61K9/146 , A61K9/1617 , A61K9/1652 , A61K9/2081 , A61K9/5042 , A61K9/5084 , A61K31/4709 , Y10S514/951 , Y10S514/952 , Y10S514/96 , Y10S514/961 , Y10S514/962 , Y10S514/963 , Y10S514/964
摘要： Provided is a cilostazol preparation which comprises incorporating a fine powder of cilostazol into a dispersing and/or solubilizing agent thereby to enhance the dispersibility and/or solubility. Further, provided is a process for improving absorbability of a slightly soluble drug such as cilostazol even at the lower portion of the digestive tract, wherein said drug is hard to be absorbed at the lower portion of the digestive tract when a conventional method is used. According to the present invention, cilostazol is absorbed enough even at the lower portion of the digestive tract to have an effect as thrombolytic drug, cerebral circulation improving drug or the like.

10. 发明公开

EP1484056A1 SUSTAINED RELEASE PREPARATIONS AND PROCESS FOR PRODUCING THE SAME 有权
标题翻译： ZUBEREITUNGEN MITVERZÖGERTERFREISETZUNG UND VERFAHRENFÜRIHRE HERSTELLUNG
公开(公告)号：EP1484056A1
公开(公告)日：2004-12-08
申请号：EP03742668.1
申请日：2003-02-20
申请人： OTSUKA PHARMACEUTICAL CO., LTD.
发明人： TOMOHIRA, Yuso
IPC分类号： A61K9/22 , A61K47/04 , A61K47/12
CPC分类号： A61K9/5015 , A61K9/1617 , A61K9/501
摘要： The present invention provides sustained-release preparations from which a pharmacologically active substance can be released over a long time and a process for producing the same. Such a sustained-release preparation is produced by melt-granulating a low-melting-point substance and a pharmacologically active substance and melt-coating the surface of the thus obtained particles with (1) a fine powder of a water-insoluble polymer or (2) a fine powder of a water-insoluble polymer and at least one member selected from the group consisting of talc, magnesium stearate and titanium oxide.
摘要翻译：本发明提供长时间释放药理活性物质的缓释制剂及其制造方法。这种缓释制剂是通过将低熔点物质和药理活性物质熔融造粒，并用（1）水不溶性聚合物的细粉末或（ 2）水不溶性聚合物的微细粉末和选自滑石，硬脂酸镁和氧化钛中的至少一种。

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