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1. 发明授权

US5663364A Heme binding compounds and use thereof 失效
标题翻译：血红素结合化合物及其用途
公开(公告)号：US5663364A
公开(公告)日：1997-09-02
申请号：US550645
申请日：1995-10-31
申请人： Owen W. Griffith , Krishnaswamy Narayanan
发明人： Owen W. Griffith , Krishnaswamy Narayanan
IPC分类号： C07D333/20 , A61K31/18 , A61K31/195 , A61K31/198 , A61P9/00 , A61P25/00 , A61P37/06 , A61P43/00 , C07C281/16 , C07C323/25 , C07C335/04 , C07C335/08 , C07D233/64 , C07D333/22 , C07D207/335
CPC分类号： C07C335/08 , C07D333/22
摘要： Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is a heme binding moiety and/or a sulfur-containing binding moiety and Q' is --NH.sub.2 when there is a double bond between the omega carbon and Q and Q' is .dbd.NH when there is a single bond between the omega carbon and Q, and physiologically acceptable acid addition salts thereof.
摘要翻译：用于治疗低血压，炎症，中风和恢复对α1肾上腺素能激动剂的作用的血管收缩敏感性的精氨酸形成一氧化氮的抑制剂是生理活性化合物，包括N-3取代的鸟氨酸或Nε-取代的赖氨酸部分或单烷基碳 - 其中R是（CH 2）y CH 3或H，R'是CH 2或C（H）（CH 2）y CH 3，R“是CH 2 或C（H）（CH 2）y CH 3，y在0至5之间，x是0或1，并且其中R，R'和R“中没有一个或只有一个在鸟氨酸或赖氨酸部分上提供烷基取代基，其中当ω-碳和Q之间存在双键时，Q是血红素结合部分和/或含硫结合部分，Q'是-NH 2，并且当ω碳之间存在单键时，Q'为= NH 和Q，及其生理上可接受的酸加成盐。

2. 发明授权

US5364881A S-alkyl-isothioureido-amino acids and use thereof 失效
标题翻译： S-烷基 - 异硫脲基 - 氨基酸及其用途
公开(公告)号：US5364881A
公开(公告)日：1994-11-15
申请号：US152010
申请日：1993-11-15
申请人： Owen W. Griffith , Krishnaswamy Narayanan
发明人： Owen W. Griffith , Krishnaswamy Narayanan
IPC分类号： C07C335/32 , A61K31/215
CPC分类号： C07C335/32
摘要： Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 -adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is alkyl having 1 to 5 carbon atoms, and physiologically acceptable acid addition salts thereof.
摘要翻译：用于治疗低血压，炎症，中风和恢复对α1-肾上腺素能激动剂作用的血管收缩敏感性的精氨酸形成一氧化氮的抑制剂是生理活性化合物，包括N-3取代的鸟氨酸或Nε-取代的赖氨酸部分或单烷基碳其中R为（CH 2）y CH 3或H，R'为CH 2或C（H）（CH 2）y CH 3，并且R“为 - 取代的N 3 - 取代的鸟氨酸或Nε-取代的赖氨酸部分 CH2或C（H）（CH2）yCH3，y范围为0至5，x为0或1，并且其中R，R'和R“中仅一个或仅一个在鸟氨酸或赖氨酸部分上提供烷基取代基，并且其中Q是具有1至5个碳原子的烷基，和其生理上可接受的酸加成盐。

3. 发明授权

US5476871A Method for the treatment of hypotension induced by a cytokine or bacterial endotoxin using s-alkyl- isothioureido-amino acids 失效
标题翻译：使用S-烷基 - 异硫脲基 - 氨基酸治疗由细胞因子或细菌内毒素引起的低血压的方法
公开(公告)号：US5476871A
公开(公告)日：1995-12-19
申请号：US302461
申请日：1994-09-12
申请人： Owen W. Griffith , Krishnaswamy Narayanan
发明人： Owen W. Griffith , Krishnaswamy Narayanan
IPC分类号： C07C335/32 , A61K31/215
CPC分类号： C07C335/32
摘要： Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 -adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is alkyl having 1 to 5 carbon atoms, and physiologically acceptable acid addition salts thereof.
摘要翻译：用于治疗低血压，炎症，中风和恢复对α1-肾上腺素能激动剂作用的血管收缩敏感性的精氨酸形成一氧化氮的抑制剂是生理活性化合物，包括N-3取代的鸟氨酸或Nε-取代的赖氨酸部分或单烷基碳其中R为（CH 2）y CH 3或H，R'为CH 2或C（H）（CH 2）y CH 3，并且R“为 - 取代的N 3 - 取代的鸟氨酸或Nε-取代的赖氨酸部分 CH2或C（H）（CH2）yCH3，y范围为0至5，x为0或1，并且其中R，R'和R“中仅一个或仅一个在鸟氨酸或赖氨酸部分上提供烷基取代基，并且其中Q是具有1至5个碳原子的烷基，和其生理上可接受的酸加成盐。

4. 发明授权

US5464858A Heme binding compounds and use thereof 失效
标题翻译：血红素结合化合物及其用途
公开(公告)号：US5464858A
公开(公告)日：1995-11-07
申请号：US354257
申请日：1994-12-12
申请人： Owen W. Griffith , Krishnaswamy Narayanan
发明人： Owen W. Griffith , Krishnaswamy Narayanan
IPC分类号： C07D333/20 , A61K31/18 , A61K31/195 , A61K31/198 , A61P9/00 , A61P25/00 , A61P37/06 , A61P43/00 , C07C281/16 , C07C323/25 , C07C335/04 , C07C335/08 , C07D233/64 , C07D333/22 , A61K31/415 , A61K31/155 , A61K31/40
CPC分类号： C07C335/08 , C07D333/22
摘要： Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is a heme binding moiety and/or a sulfur-containing binding moiety and Q' is --NH.sub.2 when there is a double bond between the omega carbon and Q and Q' is .dbd.NH when there is a single bond between the omega carbon and Q, and physiologically acceptable acid addition salts thereof.
摘要翻译：用于治疗低血压，炎症，中风和恢复对α1肾上腺素能激动剂的作用的血管收缩敏感性的精氨酸形成一氧化氮的抑制剂是生理活性化合物，包括N-3取代的鸟氨酸或Nε-取代的赖氨酸部分或单烷基碳 - 其中R是（CH 2）y CH 3或H，R'是CH 2或C（H）（CH 2）y CH 3，R“是CH 2 或C（H）（CH 2）y CH 3，y在0至5之间，x是0或1，并且其中R，R'和R“中没有一个或只有一个在鸟氨酸或赖氨酸部分上提供烷基取代基，其中当ω-碳和Q之间存在双键时，Q是血红素结合部分和/或含硫结合部分，Q'是-NH 2，并且当ω碳之间存在单键时，Q'为= NH 和Q，及其生理上可接受的酸加成盐。

5. 发明授权

US5424447A Heme binding compounds and use thereof 失效
标题翻译：血红素结合化合物及其用途
公开(公告)号：US5424447A
公开(公告)日：1995-06-13
申请号：US87371
申请日：1993-07-07
申请人： Owen W. Griffith , Krishnaswamy Narayanan
发明人： Owen W. Griffith , Krishnaswamy Narayanan
IPC分类号： C07D333/20 , A61K31/18 , A61K31/195 , A61K31/198 , A61P9/00 , A61P25/00 , A61P37/06 , A61P43/00 , C07C281/16 , C07C323/25 , C07C335/04 , C07C335/08 , C07D233/64 , C07D333/22 , C07D333/12 , C07C229/26 , C07C321/02
CPC分类号： C07C335/08 , C07D333/22
摘要： Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H) (CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H) (CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is a heme binding moiety and/or a sulfur-containing binding moiety and Q' is --NH.sub.2 when there is a double bond between the omega carbon and Q and Q' is .dbd.NH when there is a single bond between the omega carbon and Q, and physiologically acceptable acid addition salts thereof.
摘要翻译：用于治疗低血压，炎症，中风和恢复对α1肾上腺素能激动剂的作用的血管收缩敏感性的精氨酸形成一氧化氮的抑制剂是生理活性化合物，包括N-3取代的鸟氨酸或Nε-取代的赖氨酸部分或单烷基碳 - 其中R是（CH 2）y CH 3或H，R'是CH 2或C（H）（CH 2）y CH 3，R“是CH 2 或C（H）（CH 2）y CH 3，y在0至5之间，x是0或1，并且其中R，R'和R“中没有一个或只有一个在鸟氨酸或赖氨酸部分上提供烷基取代基，其中当ω-碳和Q之间存在双键时，Q是血红素结合部分和/或含硫结合部分，Q'是-NH 2，并且当ω碳之间存在单键时，Q'为= NH 和Q，及其生理上可接受的酸加成盐。

6. 发明授权

US08722091B2 Preparation of submicron sized nanoparticles via dispersion lyophilization 有权
标题翻译：通过分散体冻干法制备亚微米尺寸的纳米颗粒
公开(公告)号：US08722091B2
公开(公告)日：2014-05-13
申请号：US10920578
申请日：2004-08-17
申请人： Sean Brynjelsen , Mark Doty , James E. Kipp , Nailesh Jayswal , Krishnaswamy Narayanan
发明人： Sean Brynjelsen , Mark Doty , James E. Kipp , Nailesh Jayswal , Krishnaswamy Narayanan
IPC分类号： A61K9/14
CPC分类号： A61K9/14 , A61K9/145 , A61K9/5169 , A61K9/5192 , B01J13/04
摘要： The present invention relates to a process for preparing submicron sized nanoparticles of a poorly water soluble compound by lyophilizing a dispersion or microdispersion of a multiphase system having an organic phase and an aqueous phase, the organic phase having the poorly water soluble organic compound therein. The method is preferably used to prepare nanoparticles of a poorly water soluble, pharmaceutically active compound suitable for in vivo delivery, particularly by parenteral routes.
摘要翻译：本发明涉及通过将具有有机相和水相的多相体系的分散体或微分散体冻干而制备难溶于水的化合物的亚微米尺寸的纳米颗粒的方法，所述有机相在其中具有差的水溶性有机化合物。该方法优选用于制备适于体内递送的水溶性差的药学活性化合物的纳米颗粒，特别是通过肠胃外途径。

7. 发明申请

US20050013868A1 Preparation of submicron sized nanoparticles via dispersion lyophilization 有权
标题翻译：通过分散体冻干法制备亚微米尺寸的纳米颗粒
公开(公告)号：US20050013868A1
公开(公告)日：2005-01-20
申请号：US10920578
申请日：2004-08-17
申请人： Sean Brynjelsen , Mark Doty , James Kipp , Nailesh Jayswal , Krishnaswamy Narayanan
发明人： Sean Brynjelsen , Mark Doty , James Kipp , Nailesh Jayswal , Krishnaswamy Narayanan
IPC分类号： A61K9/14 , A61K9/19 , A61K9/51 , A61K31/496 , A61K45/00 , A61K47/10 , A61K47/12 , A61K47/14 , A61K47/18 , A61K47/20 , A61K47/24 , A61K47/28 , A61K47/32 , A61K47/34 , A61K47/36 , A61K47/38 , A61K47/42 , B01J13/04
CPC分类号： A61K9/14 , A61K9/145 , A61K9/5169 , A61K9/5192 , B01J13/04
摘要： The present invention relates to a process for preparing submicron sized nanoparticles of a poorly water soluble compound by lyophilizing a dispersion or microdispersion of a multiphase system having an organic phase and an aqueous phase, the organic phase having the poorly water soluble organic compound therein. The method is preferably used to prepare nanoparticles of a poorly water soluble, pharmaceutically active compound suitable for in vivo delivery, particularly by parenteral routes.
摘要翻译：本发明涉及通过将具有有机相和水相的多相体系的分散体或微分散体冻干而制备难溶于水的化合物的亚微米尺寸的纳米颗粒的方法，所述有机相在其中具有差的水溶性有机化合物。该方法优选用于制备适于体内递送的水溶性差的药学活性化合物的纳米颗粒，特别是通过肠胃外途径。

8. 发明授权

US06835396B2 Preparation of submicron sized nanoparticles via dispersion lyophilization 有权
标题翻译：通过分散体冻干法制备亚微米尺寸的纳米颗粒
公开(公告)号：US06835396B2
公开(公告)日：2004-12-28
申请号：US10183035
申请日：2002-06-26
申请人： Sean Brynjelsen , Mark Doty , James E. Kipp , Nailesh Jayswal , Krishnaswamy Narayanan
发明人： Sean Brynjelsen , Mark Doty , James E. Kipp , Nailesh Jayswal , Krishnaswamy Narayanan
IPC分类号： A61F1300
CPC分类号： A61K9/5169 , A61K9/5192
摘要： The present invention relates to a process for preparing submicron sized nanoparticles of a poorly water soluble compound by lyophilizing a dispersion or microdispersion of a multiphase system having an organic phase and an aqueous phase, the organic phase having the poorly water soluble organic compound therein. The method is preferably used to prepare nanoparticles of a poorly water soluble, pharmaceutically active compound suitable for in vivo delivery, particularly by parenteral routes.
摘要翻译：本发明涉及通过将具有有机相和水相的多相体系的分散体或微分散体冻干而制备难溶于水的化合物的亚微米尺寸的纳米颗粒的方法，所述有机相在其中具有差的水溶性有机化合物。该方法优选用于制备适于体内递送的水溶性差的药学活性化合物的纳米颗粒，特别是通过肠胃外途径。

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