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1. 发明申请

US20090047357A1 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：生产含有糖尿病基质颗粒的方法，用于方法中使用的挤出机和含有CILOSTAZOL的持续释放制剂
公开(公告)号：US20090047357A1
公开(公告)日：2009-02-19
申请号：US12158529
申请日：2006-12-21
申请人： Yuso Tomohira , Yasuo Yamaguchi
发明人： Yuso Tomohira , Yasuo Yamaguchi
IPC分类号： A61K9/14 , B29B9/12 , A61K31/4709 , B28B17/00
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一种通过简单的方法制备平均粒径为1mm以下的含药蜡基质颗粒，特别是含有药物的蜡基质颗粒，同时避免由于重结晶引起的液体堵塞在熔融步骤至喷雾步骤期间的熔融药物。通过以下步骤（i）和（ii）制备具有至少一种蜡和至少一种药物的含药蜡基质颗粒：（i）将至少一种药物和至少一种蜡供应到挤出机中，其中桶的温度和模具的温度被调节为高于至少一种蜡的熔点; 和（ii）在挤出机中熔融和捏合至少一种药物和至少一种蜡以得到熔融捏合药物和蜡，将熔融捏合药物和蜡喷雾到温度低于来自喷嘴的蜡直接安装在设置在挤出机的桶的顶端的模具上，从而将混合物形成颗粒。

2. 发明授权

US08703189B2 Medicinal composition 失效
标题翻译：药用成分
公开(公告)号：US08703189B2
公开(公告)日：2014-04-22
申请号：US10477427
申请日：2002-05-23
申请人： Yuso Tomohira
发明人： Yuso Tomohira
IPC分类号： A61K9/22 , A61K9/26 , A61K9/14 , A61K9/50
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：本发明提供一种药物组合物，其显示出优异的储存稳定性，并且即使在长期储存中，其中所含的药理活性物质的释放速率也几乎没有变化。通过将药理活性物质和pH非依赖性水不溶性聚合物溶解或分散在熔融低熔点物质中制备的本发明的药物组合物，其可以通过将药物溶解或分散得到的液体物质喷雾在包含低熔点物质和pH非依赖性水不溶性聚合物的熔融混合物中的活性物质，然后冷却液体物质。

3. 发明申请

US20110071084A1 BENZAZEPINE DERIVATIVES USEFUL AS VASOPRESSIN ANTAGONISTS 有权
标题翻译：苯并噻吩衍生物可用作VASOPRESSIN拮抗剂
公开(公告)号：US20110071084A1
公开(公告)日：2011-03-24
申请号：US12666751
申请日：2008-06-26
申请人： Kazumi Kondo , Yasuhiro Menjo , Takahiro Tomoyasu , Shin Miyamura , Yuso Tomohira , Takakuni Matsuda , Keigo Yamada , Yusuke Kato
发明人： Kazumi Kondo , Yasuhiro Menjo , Takahiro Tomoyasu , Shin Miyamura , Yuso Tomohira , Takakuni Matsuda , Keigo Yamada , Yusuke Kato
IPC分类号： A61K31/55 , C07D223/16 , C07D403/12 , C07F9/553 , C07D405/12 , C07D413/12 , C07D401/12 , C07D405/14 , C07K5/083 , A61K31/675 , A61K38/06 , A61K38/05 , A61P9/12 , A61P9/00 , A61P7/02
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 R1 represents a —CO—(CH2)n—COR2 group (wherein n is an integer of 1 to 4, and R2 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-dioxo-4-yl; or (2-3) an amino group optionally substituted with a hydroxy-lower alkyl group), or the like.
摘要翻译：本发明提供苯并氮杂化合物，其可以长时间保持托伐普坦的血液水平，从而能够提供所需的药物作用。本发明的苯并氮杂化合物由通式（1）表示，其中R1表示-CO-（CH2）n-COR2基团（其中n为1〜4的整数，R2为（2-1）羟基基团;（2-2）任选被羟基，低级烷酰基，低级烷酰氧基，低级烷氧基羰基氧基，环烷氧基羰基氧基或5-甲基-2-氧代-1,3-二氧戊环的低级烷氧基，二氧代-4-基;或（2-3）任选被羟基 - 低级烷基取代的氨基）等。

4. 发明申请

US20070098843A1 Medicament sustained-release particles and method for preparing the same 有权
标题翻译：药物缓释颗粒及其制备方法
公开(公告)号：US20070098843A1
公开(公告)日：2007-05-03
申请号：US10561444
申请日：2004-06-17
申请人： Yuso Tomohira
发明人： Yuso Tomohira
IPC分类号： A23G4/18
CPC分类号： A61K9/1617 , A61K9/145 , A61K9/146 , A61K9/1641 , A61K9/1652 , A61K9/501 , A61K9/5047 , A61K31/522
摘要： The present invention provides theophylline sustained release particles which contain a polyglycerol fatty acid ester as a matrix base material, which have a homogenous nucleus particle structure, which can effectively mask the unpleasant taste of medicaments, and which exhibit an excellent sustained medicament releasability (dissolvability) and outstanding storage stability. In particular, the present invention provides, among other things, a method for preparing theophylline sustained release particles comprising the steps of heating a matrix base material containing a polyglycerol fatty acid ester, theophylline and ethyl cellulose to give a molten mixture; spray-cooling the molten mixture to obtain spherical core particles having an average particle diameter of 250 μm or less; and applying fine particles to the core particles by fusion coating.
摘要翻译：本发明提供了含有聚甘油脂肪酸酯作为基质材料的茶碱缓释颗粒，其具有均匀的核颗粒结构，其可以有效地掩盖药物的令人不快的味道，并且显示出优异的持续药物释放性（溶解性）并具有出色的储存稳定性。特别地，本发明尤其提供了一种制备茶碱缓释颗粒的方法，包括以下步骤：加热含有聚甘油脂肪酸酯，茶碱和乙基纤维素的基质基料，得到熔融混合物; 将熔融混合物喷雾冷却，得到平均粒径为250μm以下的球状核粒子; 并通过熔融涂覆将细颗粒施加到芯颗粒。

5. 发明授权

US08796309B2 Pharmaceutical composition achieving excellent absorbency of pharmacologically active substance 有权
标题翻译：具有优异药理活性物质吸收性的药物组合物
公开(公告)号：US08796309B2
公开(公告)日：2014-08-05
申请号：US12084483
申请日：2006-11-02
申请人： Yasuo Yamaguchi , Takakuni Matsuda , Yuso Tomohira
发明人： Yasuo Yamaguchi , Takakuni Matsuda , Yuso Tomohira
IPC分类号： A61K31/445
CPC分类号： A61K47/14 , A61K9/0053 , A61K31/454 , A61K47/12
摘要： The present invention provides a pharmaceutical composition that can efficiently achieve its medicinal action by having excellent basic pharmacologically active substance absorbency, even the basic pharmacologically active substance is poorly soluble, the pharmaceutical composition being prepared by adding (i) a basic pharmacologically active substance together with (ii) a fatty acid and organic acid glycerol ester and/or fatty acid and organic acid polyglycerol ester.
摘要翻译：本发明提供能够通过具有优异的碱性药理活性物质吸收性而有效地实现其药用作用的药物组合物，即使碱性药理活性物质难溶，药物组合物通过将（i）碱性药理活性物质与（ii）脂肪酸和有机酸甘油酯和/或脂肪酸和有机酸聚甘油酯。

6. 发明授权

US08669229B2 Benzazepine derivatives useful as vasopressin antagonists 有权
标题翻译：苯并氮平衍生物可用作加压素拮抗剂
公开(公告)号：US08669229B2
公开(公告)日：2014-03-11
申请号：US12666751
申请日：2008-06-26
申请人： Kazumi Kondo , Yasuhiro Menjo , Takahiro Tomoyasu , Shin Miyamura , Yuso Tomohira , Takakuni Matsuda , Keigo Yamada , Yusuke Kato
发明人： Kazumi Kondo , Yasuhiro Menjo , Takahiro Tomoyasu , Shin Miyamura , Yuso Tomohira , Takakuni Matsuda , Keigo Yamada , Yusuke Kato
IPC分类号： A61K38/00 , C07D223/16
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 R1 represents a —CO—(CH2)n—COR2 group (wherein n is an integer of 1 to 4, and R2 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-dioxo-4-yl; or (2-3) an amino group optionally substituted with a hydroxy-lower alkyl group), or the like.
摘要翻译：本发明提供苯并氮杂化合物，其可以长时间保持托伐普坦的血液水平，从而能够提供所需的药物作用。本发明的苯并氮杂化合物由通式（1）表示，其中R1表示-CO-（CH2）n-COR2基团（其中n为1〜4的整数，R2为（2-1）羟基基团;（2-2）任选被羟基，低级烷酰基，低级烷酰氧基，低级烷氧基羰基氧基，环烷氧基羰基氧基或5-甲基-2-氧代-1,3-二氧戊环的低级烷氧基，二氧代-4-基;或（2-3）任选被羟基 - 低级烷基取代的氨基）等。

7. 发明申请

US20090227630A1 Pharmaceutical Composition Achieving Excellent Absorbency of Pharmacologically Active Substance 有权
标题翻译：药物组合物具有优异的药理活性物质吸收性
公开(公告)号：US20090227630A1
公开(公告)日：2009-09-10
申请号：US12084483
申请日：2006-11-02
申请人： Yasuo Yamaguchi , Takakuni Matsuda , Yuso Tomohira
发明人： Yasuo Yamaguchi , Takakuni Matsuda , Yuso Tomohira
IPC分类号： A61K31/454 , A61P35/00
CPC分类号： A61K47/14 , A61K9/0053 , A61K31/454 , A61K47/12
摘要： The present invention provides a pharmaceutical composition that can efficiently achieve its medicinal action by having excellent basic pharmacologically active substance absorbency, even the basic pharmacologically active substance is poorly soluble, the pharmaceutical composition being prepared by adding (i) a basic pharmacologically active substance together with (ii) a fatty acid and organic acid glycerol ester and/or fatty acid and organic acid polyglycerol ester.
摘要翻译：本发明提供能够通过具有优异的碱性药理活性物质吸收性而有效地实现其药用作用的药物组合物，即使碱性药理活性物质难溶，药物组合物通过将（i）碱性药理活性物质与（ii）脂肪酸和有机酸甘油酯和/或脂肪酸和有机酸聚甘油酯。

8. 发明授权

US07144585B1 Cilostazol preparation 有权
标题翻译：西洛他唑制剂
公开(公告)号：US07144585B1
公开(公告)日：2006-12-05
申请号：US09555026
申请日：2000-03-21
申请人： Tadashi Mukai , Yuso Tomohira , Masafumi Toda , Keigo Yamada , Yoshikazu Oka
发明人： Tadashi Mukai , Yuso Tomohira , Masafumi Toda , Keigo Yamada , Yoshikazu Oka
IPC分类号： A61K9/14 , A61K9/20 , A61K9/48
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.
摘要翻译：提供了一种西洛他唑制剂，其包括将细西洛他唑的细粉末掺入分散和/或增溶剂中，从而提高分散性和/或溶解度。此外，提供了即使在消化道的下部也提高微溶药物例如西洛他唑的吸收性的方法，其中当使用常规方法时，所述药物难以在消化道下部被吸收。根据本发明，西洛他唑即使在消化道下部也被吸收，具有作为溶栓药物，大脑循环改善药物等的作用。

9. 发明授权

US08734843B2 Medicament sustained-release particles and method for preparing the same 有权
标题翻译：药物缓释颗粒及其制备方法
公开(公告)号：US08734843B2
公开(公告)日：2014-05-27
申请号：US10561444
申请日：2004-06-17
申请人： Yuso Tomohira
发明人： Yuso Tomohira
IPC分类号： A61K9/14 , A61K9/16 , A61K9/22
CPC分类号： A61K9/1617 , A61K9/145 , A61K9/146 , A61K9/1641 , A61K9/1652 , A61K9/501 , A61K9/5047 , A61K31/522
摘要： The present invention provides theophylline sustained release particles which contain a polyglycerol fatty acid ester as a matrix base material, which have a homogenous nucleus particle structure, which can effectively mask the unpleasant taste of medicaments, and which exhibit an excellent sustained medicament releasability (dissolvability) and outstanding storage stability. In particular, the present invention provides, among other things, a method for preparing theophylline sustained release particles comprising the steps of heating a matrix base material containing a polyglycerol fatty acid ester, theophylline and ethyl cellulose to give a molten mixture; spray-cooling the molten mixture to obtain spherical core particles having an average particle diameter of 250 μm or less; and applying fine particles to the core particles by fusion coating.
摘要翻译：本发明提供了含有聚甘油脂肪酸酯作为基质材料的茶碱缓释颗粒，其具有均匀的核颗粒结构，其可以有效地掩盖药物的令人不快的味道，并且显示出优异的持续药物释放性（溶解性）并具有出色的储存稳定性。特别地，本发明尤其提供了一种制备茶碱缓释颗粒的方法，包括以下步骤：加热含有聚甘油脂肪酸酯，茶碱和乙基纤维素的基质基料，得到熔融混合物; 将熔融混合物喷雾冷却，得到平均粒径为250μm以下的球状核粒子; 并通过熔融涂覆将细颗粒施加到芯颗粒。

10. 发明授权

US07867514B2 Method for stabilizing preparation 有权
标题翻译：稳定制剂的方法
公开(公告)号：US07867514B2
公开(公告)日：2011-01-11
申请号：US10276294
申请日：2001-05-23
申请人： Yuso Tomohira , Tadashi Mukai , Minoru Kashimoto , Masakazu Nagasawa , Tetsuroh Ichiba , Daisuke Kuribayashi , Yoshikazu Oka , Hajime Toguchi
发明人： Yuso Tomohira , Tadashi Mukai , Minoru Kashimoto , Masakazu Nagasawa , Tetsuroh Ichiba , Daisuke Kuribayashi , Yoshikazu Oka , Hajime Toguchi
IPC分类号： A61K9/14 , A61K9/20 , A61K9/48
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：公开了一种用于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。

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