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1. 发明授权

US06440458B1 Sustained release preparations 有权
公开(公告)号：US06440458B1
公开(公告)日：2002-08-27
申请号：US09403787
申请日：1999-11-05
申请人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
发明人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
IPC分类号： A61K922
CPC分类号： A61K31/453 , A61K9/141 , A61K9/143 , A61K9/145 , A61K9/146 , A61K9/1617 , A61K9/1623 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K9/1652 , A61K9/4858 , A61K31/407 , A61K31/436
摘要： Providing an oral formulation of a macrolide compound where the dissolution of the macrolide compound is under sustained release; and a sustained-release formulation containing a composition in solid solution, where the macrolide compound is present at an amorphous state in a solid base.

2. 发明授权

US08551522B2 Sustained-release formulation 有权
标题翻译：持续释放制剂
公开(公告)号：US08551522B2
公开(公告)日：2013-10-08
申请号：US12265108
申请日：2008-11-05
申请人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
发明人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
IPC分类号： A61K9/00 , A61K9/14 , A61K9/66 , C12N11/00
CPC分类号： A61K31/453 , A61K9/141 , A61K9/143 , A61K9/145 , A61K9/146 , A61K9/1617 , A61K9/1623 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K9/1652 , A61K9/4858 , A61K31/407 , A61K31/436
摘要： A sustained-release formulation is provided comprising a solid dispersion composition comprising a tricyclic compound or a pharmaceutically acceptable salt thereof in a mixture comprising a water-soluble polymer and a water-insoluble polymer, and an excipient.
摘要翻译：提供了包含在包含水溶性聚合物和水不溶性聚合物和赋形剂的混合物中的包含三环化合物或其药学上可接受的盐的固体分散体组合物的缓释制剂。

3. 发明授权

US06884433B2 Sustained release formulation containing tacrolimus 有权
标题翻译：含有他克莫司的缓释制剂
公开(公告)号：US06884433B2
公开(公告)日：2005-04-26
申请号：US10412281
申请日：2003-04-14
申请人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
发明人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
IPC分类号： C07H15/04 , A61K20060101 , A61K9/10 , A61K9/14 , A61K9/16 , A61K9/20 , A61K9/22 , A61K9/48 , A61K9/52 , A61K31/40 , A61K31/405 , A61K31/407 , A61K31/4353 , A61K31/436 , A61K31/453 , A61K31/706 , A61K47/04 , A61K47/12 , A61K47/14 , A61K47/26 , A61K47/32 , A61K47/36 , A61K47/38 , A61K47/40 , A61P31/00 , A61P37/06 , C07D498/18 , G01N33/15 , A61K9/00 , A61K31/44
CPC分类号： A61K31/453 , A61K9/141 , A61K9/143 , A61K9/145 , A61K9/146 , A61K9/1617 , A61K9/1623 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K9/1652 , A61K9/4858 , A61K31/407 , A61K31/436
摘要： Sustained release formulation containing tacrolimus or its hydrate is provided. The time (T63.2%) required for 63.2% of the maximum amount of tacrolimus or its hydrate to be dissolved is 0.7 to 15 hours. The time is measured in accordance to the Japanes Pharmacopocia, the 13-th edition, Dissolution Test, No. 2 (Puddles method, 50 rpm) using an aqueous 0.005% hydroxypropyl cellulose solution. This aqueous test solution is adjusted to pH 4.5, accordingly. The formulation further comprises a solid base which is a water-soluble or water-insoluble polymer. The formulation is in the form of a powder, fine powder, granule, tablet or capsule. The formulation is administered to a patient once a day for preventing organ or tissue rejection by transplantation or autoimmune disease. In addition, a solid dispersion composition is provided. The solid dispersion comprises tacrolimus or its hydrate in a mixture containing water-soluble or water-insoluble polymer and an excipient.
摘要翻译：提供含他克莫司或其水合物的缓释制剂。最高量的他克莫司或其水合物溶解63.2％所需的时间（T63.2％）为0.7〜15小时。该时间根据Japanes Pharmacopocia，第13版，溶出度试验，2号（Puddles法，50rpm），使用0.005％羟丙基纤维素水溶液测量。相应地将该水性测试溶液调节至pH 4.5。该制剂还包含固体碱，其为水溶性或水不溶性聚合物。制剂为粉末，细粉，颗粒，片剂或胶囊的形式。该制剂每天一次施用于患者，以通过移植或自身免疫疾病预防器官或组织排斥反应。此外，提供了固体分散体组合物。固体分散体包含他克莫司或其水合物，其含有水溶性或水不溶性聚合物和赋形剂的混合物。

4. 发明申请

US20050169993A1 Sustained-release formulation 审中-公开
标题翻译：持续释放制剂
公开(公告)号：US20050169993A1
公开(公告)日：2005-08-04
申请号：US11059439
申请日：2005-02-17
申请人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
发明人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
IPC分类号： C07H15/04 , A61K20060101 , A61K9/10 , A61K9/14 , A61K9/16 , A61K9/20 , A61K9/22 , A61K9/48 , A61K9/52 , A61K31/40 , A61K31/405 , A61K31/407 , A61K31/4353 , A61K31/436 , A61K31/453 , A61K31/706 , A61K47/04 , A61K47/12 , A61K47/14 , A61K47/26 , A61K47/32 , A61K47/36 , A61K47/38 , A61K47/40 , A61P31/00 , A61P37/06 , C07D498/18 , G01N33/15 , A61K31/4745
CPC分类号： A61K31/453 , A61K9/141 , A61K9/143 , A61K9/145 , A61K9/146 , A61K9/1617 , A61K9/1623 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K9/1652 , A61K9/4858 , A61K31/407 , A61K31/436
摘要： A sustained-release formulation is provided comprising a solid dispersion composition comprising a tricyclic compound or a pharmaceutically acceptable salt thereof in a mixture comprising a water-soluble polymer and a water-insoluble polymer, and an excipient.
摘要翻译：提供了包含在包含水溶性聚合物和水不溶性聚合物和赋形剂的混合物中的包含三环化合物或其药学上可接受的盐的固体分散体组合物的缓释制剂。

5. 发明授权

US06576259B2 Sustained release formulations containing tacrolimus 有权
标题翻译：含有他克莫司的缓释制剂
公开(公告)号：US06576259B2
公开(公告)日：2003-06-10
申请号：US09978025
申请日：2001-10-17
申请人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
发明人： Kazunari Yamashita , Eiji Hashimoto , Yukihiro Nomura , Fumio Shimojo , Shigeki Tamura , Takeo Hirose , Satoshi Ueda , Takashi Saitoh , Rinta Ibuki , Toshio Ideno
IPC分类号： A61K900
CPC分类号： A61K31/453 , A61K9/141 , A61K9/143 , A61K9/145 , A61K9/146 , A61K9/1617 , A61K9/1623 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K9/1652 , A61K9/4858 , A61K31/407 , A61K31/436
摘要： Sustained release formulation containing tacrolimus or its hydrate is provided. The time (T63.2%) required for 63.2% of the maximum amount of tacrolimus or its hydrate to be dissolved is 0.7 to 15 hours. The time is measured in accordance to the Japanese Pharmacopoeia, the 13-th edition, Dissolution Test, No. 2 (Puddle method, 50 rpm) using an aqueous 0.005% hydroxypropyl cellulose solution. This aqueous test solution is adjusted to pH 4.5, accordingly. The formulation further comprise a solid base which is a water-soluble polymer and/or wax. The formulation is in the form of a powder, fine powder, granule, tablet or capsule. Furthermore, the formulation is administered to a patient once a day for preventing organ or tissue rejection by transplantation or autoimmune diseases.
摘要翻译：提供含他克莫司或其水合物的缓释制剂。最高量的他克莫司或其水合物溶解63.2％所需的时间（T63.2％）为0.7〜15小时。时间根据日本药典，第13版，溶出度试验，第2号（Puddle法，50rpm），使用0.005％羟丙基纤维素水溶液测量。相应地将该水性测试溶液调节至pH 4.5。制剂还包含固体碱，其为水溶性聚合物和/或蜡。制剂为粉末，细粉，颗粒，片剂或胶囊的形式。此外，该制剂每天一次施用于患者，以通过移植或自身免疫疾病预防器官或组织排斥反应。

6. 发明授权

US06838470B2 Arylpiperidinopropanol and arylpiprazinopropanol derivatives and pharmaceuticals containing the same 失效
标题翻译：芳基哌啶丙醇和芳基哌嗪丙醇衍生物和含有它们的药物
公开(公告)号：US06838470B2
公开(公告)日：2005-01-04
申请号：US10331508
申请日：2002-12-31
申请人： Hirokazu Annoura , Kyoko Nakanishi , Shigeki Tamura
发明人： Hirokazu Annoura , Kyoko Nakanishi , Shigeki Tamura
IPC分类号： A61P25/04 , A61K31/451 , A61K31/495 , A61P3/10 , A61P9/10 , A61P25/28 , C07C217/84 , C07C271/28 , C07D211/18 , C07D211/22 , C07D211/52 , C07D295/08 , C07D295/092 , C07D295/13 , C07D295/135
CPC分类号： C07D295/088 , C07C217/84 , C07C271/28 , C07D211/22 , C07D211/52 , C07D295/13 , Y02P20/55
摘要： A compound having the formula (I) or its salt, hydrate, hydrate salt or solvate: wherein R1 to R4 independently represent H, halogen, OH, alkoxy, optionally substituted alkyl, aryl, or aralkyl group, R5 represents H, optionally substituted alkyl, aryl, or aralkyl group, E1 represents O, S, or —NR6, where R6 represents H, an optionally substituted alkyl, aryl, or aralkyl group, E2 represents O, S, or —NR7, where R7 represents H, an optionally substituted alkyl, aryl, or aralkyl group, A represents CH, C(OH), or N, X represents H, halogen, alkoxy, or an optionally substituted alkyl group, and Q represents an optionally substituted phenyl group, phenoxy, phenylmethyl, or cycloalkyloxy group, where when E1 represents O or S, E2 does not represent O or S, which has an action of suppressing the cytotoxic Ca2+ overload and lipid peroxidation and effective for pharmaceutical preparation for the alleviation and treatment of symptoms due to ischemic diseases, etc.
摘要翻译：具有式（I）的化合物或其盐，水合物，水合物盐或溶剂化物：其中R 1至R 4独立地表示H，卤素，OH，烷氧基，任选取代的烷基，芳基或芳烷基，R 代表H，任选取代的烷基，芳基或芳烷基，E 1表示O，S或-NR 6，其中R 6表示H，任选取代的烷基，芳基或芳烷基，E 2表示O，S或-NR 7，其中R 7表示H，任选取代的烷基，芳基或芳烷基，A表示CH，C（OH）或N，X表示 H，卤素，烷氧基或任选取代的烷基，Q表示任选取代的苯基，苯氧基，苯甲基或环烷氧基，其中当E 1表示O或S时，E 2不表示O或 S具有抑制细胞毒性Ca 2+过载和脂质过氧化的作用，并且对于由于缺血性疾病等引起的症状缓解和治疗药物制剂有效。

7. 发明授权

US06455549B1 Arylpiperidinol and arylpiperidine derivatives and drugs containing the same 失效
标题翻译：芳基哌啶醇和芳基哌啶衍生物和含有相同的药物
公开(公告)号：US06455549B1
公开(公告)日：2002-09-24
申请号：US09043563
申请日：1998-03-20
申请人： Hirokazu Annoura , Kyoko Nakanishi , Shigeki Tamura
发明人： Hirokazu Annoura , Kyoko Nakanishi , Shigeki Tamura
IPC分类号： A61K31445
CPC分类号： C07D211/44 , C07D211/12 , C07D211/14 , C07D211/18 , C07D211/52 , C07D211/70
摘要： A pharmaceutical composition, especially a pharmaceutical composition for the alleviation or treatment of symptoms due to ischemic diseases and symptoms derived from seizures, epilepsy, and migraine, and a Ca2+ overload suppressant, containing an arylpiperidinol or arylpiperidine derivative having the formula (I): wherein, R is H, an optionally substituted phenyl, an optionally substituted phenoxy, or an optionally substituted benzoyl, A is a connecting bond, a cycloalkylene, or an alkenylene optionally substituted with a lower alkyl, B is an alkylene optionally substituted with OH or an alkoxy or —NHCO(CH2)n— where n is an integer of 1 to 5, E is a connecting bond, O, or a methylene, X is OH or H provided that when E is O or a methylene, X is not H, and Y and Z are independently H, a halogen, an alkoxy, or an alkyl optionally substituted with a halogen.
摘要翻译：一种药物组合物，特别是用于缓解或治疗由于缺血性疾病引起的症状和由癫痫发作，癫痫和偏头痛引起的症状的药物组合物和含有具有式（I）的芳基哌啶醇或芳基哌啶衍生物的Ca2 +过量抑制剂：其中 R是H，任意取代的苯基，任意取代的苯氧基或任选取代的苯甲酰基，A是任选被低级烷基取代的连接键，亚环烷基或亚烯基，B是任选被OH取代的亚烷基或烷氧基或-NHCO（CH 2）n - ，其中n为1至5的整数，E为连接键，O或亚甲基，X为OH或H，条件是当E为O或亚甲基时，X不为H ，Y和Z独立地为H，卤素，烷氧基或任选被卤素取代的烷基。

8. 发明授权

US5957190A Method of integrally attaching hollow member to cast product by casting and apparatus therefor 失效
标题翻译：通过铸造将中空构件一体地安装到铸造产品上的方法及其装置
公开(公告)号：US5957190A
公开(公告)日：1999-09-28
申请号：US922341
申请日：1997-09-03
申请人： Hisaya Morishita , Akira Seki , Shigeki Tamura , Mitsuru Inui
发明人： Hisaya Morishita , Akira Seki , Shigeki Tamura , Mitsuru Inui
IPC分类号： B22D17/22 , B22D19/00
CPC分类号： B22D19/0072
摘要： In a method of integrally attaching a hollow member to a cast product by casting so that the hollow member communicates with a hollow interior of the cast product, a closure member is fitted into an open end of the hollow member so that the open end of the hollow member is closed by the closure member. The closure member projects from a core for forming the hollow interior of the cast product in a direction different from a direction in which the core is drawn out of the cast product. A molten metal is poured into a casting mold after the casting mold has been clamped. The closure member is moved inside the core after solidification of the molten metal so that the closure member is released from the fitting in the hollow member. The core is drawn out of the solidified metal subsequently to the moving step of the closure member.
摘要翻译：在通过铸造将中空构件整体地附接到铸造产品的方法中，使得中空构件与铸造产品的中空内部连通，将封闭构件装配到中空构件的开口端中，使得开口端中空构件被封闭构件封闭。封闭构件从用于形成铸造产品的中空内部的芯部沿与芯从铸造产品中拉出的方向不同的方向突出。在铸模被夹紧后，将熔融金属倒入铸模中。在熔融金属凝固之后，封闭构件在芯内移动，使得封闭构件从中空构件中的配件释放。随后在封闭构件的移动步骤之后，将芯体从固化的金属中拉出。

9. 发明授权

US07498344B2 Arylpiperidinol and arylpiperidine derivatives and pharmaceuticals containing the same 失效
标题翻译：芳基哌啶醇和芳基哌啶衍生物和含有它们的药物
公开(公告)号：US07498344B2
公开(公告)日：2009-03-03
申请号：US10799681
申请日：2004-03-15
申请人： Hirokazu Annoura , Kyoko Nakanishi , Shigeki Tamura
发明人： Hirokazu Annoura , Kyoko Nakanishi , Shigeki Tamura
IPC分类号： A61K31/4465 , C07D211/22 , C07D211/40
CPC分类号： C07D211/44 , C07D211/12 , C07D211/14 , C07D211/18 , C07D211/52 , C07D211/70
摘要： A pharmaceutical composition, especially a pharmaceutical composition for the alleviation or treatment of symptoms due to ischemic diseases and symptoms derived from seizures, epilepsy, and migraine, and a Ca2+ overload suppressant, containing an arylpiperidinol or arylpiperidine derivative having the formula (I): wherein, R is H, an optionally substituted phenyl, an optionally substituted phenoxy, or an optionally substituted benzoyl, A is a connecting bond, a cycloalkylene, or an alkenylene optionally substituted with a lower alkyl, B is an alkylene optionally substituted with OH or an alkoxy or —NHCO(CH2)n— where n is an integer of 1 to 5, E is a connecting bond, O, or a methylene, X is OH or H provided that when E is O or a methylene, X is not H, and Y and Z are independently H, a halogen, an alkoxy, or an alkyl optionally substituted with a halogen.
摘要翻译：一种药物组合物，特别是用于缓解或治疗由于缺血性疾病引起的症状和由癫痫发作，癫痫和偏头痛引起的症状的药物组合物和含有具有式（I）的芳基哌啶醇或芳基哌啶衍生物的Ca2 +过量抑制剂：其中 R是H，任意取代的苯基，任意取代的苯氧基或任选取代的苯甲酰基，A是任选被低级烷基取代的连接键，亚环烷基或亚烯基，B是任选被OH取代的亚烷基或烷氧基或-NHCO（CH 2）n - ，其中n为1至5的整数，E为连接键，O或亚甲基，X为OH或H，条件是当E为O或亚甲基时，X不为H ，Y和Z独立地为H，卤素，烷氧基或任选被卤素取代的烷基。

10. 发明申请

US20050101610A1 Arylipiperdinopropanol and arylipiperazinopropanol derivatives and pharmaceuticals containing the same 失效
标题翻译：芳基哌啶丙醇和芳基哌嗪丙醇衍生物和含有它们的药物
公开(公告)号：US20050101610A1
公开(公告)日：2005-05-12
申请号：US11002793
申请日：2004-12-03
申请人： Hirokazu Annoura , Kyoko Nakanishi , Shigeki Tamura
发明人： Hirokazu Annoura , Kyoko Nakanishi , Shigeki Tamura
IPC分类号： A61P25/04 , A61K31/451 , A61K31/495 , A61P3/10 , A61P9/10 , A61P25/28 , C07C217/84 , C07C271/28 , C07D211/18 , C07D211/22 , C07D211/52 , C07D295/08 , C07D295/092 , C07D295/13 , A61K31/445 , C07D211/20 , C07D241/04
CPC分类号： C07D295/088 , C07C217/84 , C07C271/28 , C07D211/22 , C07D211/52 , C07D295/13 , Y02P20/55
摘要： A compound having the formula (I) or its salt, hydrate, hydrate salt or solvate: wherein R1 to R4 independently represent H, halogen, OH, alkoxy, optionally substituted alkyl, aryl, or aralkyl group, R5 represents H, optionally substituted alkyl, aryl, or aralkyl group, E1 represents O, S, or —NR6, where R6 represents H, an optionally substituted alkyl, aryl, or aralkyl group, E2 represents O, S, or —NR7, where R7 represents H, an optionally substituted alkyl, aryl, or aralkyl group, A represents CH, C(OH), or N, X represents H, halogen, alkoxy, or an optionally substituted alkyl group, and Q represents an optionally substituted phenyl group, phenoxy, phenylmethyl, or cycloalkyloxy group, where when E1 represents O or S, E2 does not represent O or S, which has an action of suppressing the cytotoxic Ca2+ overload and lipid peroxidation and effective for pharmaceutical preparation for the alleviation and treatment of symptoms due to ischemic diseases, etc.
摘要翻译：具有式（I）的化合物或其盐，水合物，水合物盐或溶剂合物：其中R 1至R 4独立地表示H，卤素，OH，烷氧基，任选地取代的烷基，芳基或芳烷基，R 5表示H，任选取代的烷基，芳基或芳烷基，E 1表示O，S或-NR > 6，其中R 6表示H，任选取代的烷基，芳基或芳烷基，E 2表示O，S或-NR

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