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1. 发明授权

US5393530A Method for making liposomes of enhanced entrapping capacity toward foreign substances to be encapsulated 失效
标题翻译：制备脂质体增强包封能力的方法
公开(公告)号：US5393530A
公开(公告)日：1995-02-28
申请号：US861889
申请日：1992-06-22
申请人： Michel Schneider , Herve Tournier , Roland Hyacinthe , Christian Guillot , Bernard Lamy
发明人： Michel Schneider , Herve Tournier , Roland Hyacinthe , Christian Guillot , Bernard Lamy
IPC分类号： A61K9/00 , A61K9/127 , A61K47/48 , A61K49/04 , B01J13/02 , A61K57/22
CPC分类号： A61K49/0466 , A61K9/1278
摘要： Liposome vesicles are prepared containing water or very dilute solutions encapsulated therein. These "empty" liposomes are suspended in a carrier liquid containing, dispersed therein, substances of interest to be loaded into the vesicles and incubated for a period of time at temperatures above the lipids transition temperature, whereby loading by transmembrane permeation occurs in high yields.
摘要翻译： PCT No.PCT / EP91 / 00377。 371日期：1992年6月22日 102（e）日期1992年6月22日PCT提交1992年12月9日PCT公布。公开号WO92 / 10166 日期：1992年6月25日。制备含有水或非常稀的溶液的脂质体囊泡。将这些“空”脂质体悬浮于含有分散在其中的感兴趣物质的载体液体中，将其装载到囊泡中，并在高于脂质转变温度的温度下温育一段时间，由此通过跨膜渗透的加载以高产率发生。

2. 发明授权

US5833948A Blood-pool imaging composition comprising micelles containing a lipophilic chelating agent and a non-ionic surfactant 失效
标题翻译：包含含有亲脂性螯合剂和非离子表面活性剂的胶束的血池成像组合物
公开(公告)号：US5833948A
公开(公告)日：1998-11-10
申请号：US663545
申请日：1996-06-13
申请人： Herve Tournier , Bernard Lamy , Roland Hyacinthe
发明人： Herve Tournier , Bernard Lamy , Roland Hyacinthe
IPC分类号： A61K49/00 , A61K49/18 , A61B5/055
CPC分类号： A61K49/1806 , Y10S514/836 , Y10S514/937
摘要： The invention concerns NMR imaging contrast compositions comprising magnetically responsive species coupled to physiologically acceptable amphipatic organic substrate materials in the form of mixed micelles suspended or dispersed in a physiologically acceptable aqueous liquid carrier. The compositions are particularly useful for diagnostic investigations of the blood-pool. The invention also concerns the preparation of the mixed micelles, as well as of injectable compositions containing the mixed micelles as contrast agents for MRI purpose. Once injected, the mixed micelles of the compositions behave as imaging contrast enhancers, e.g. they will improve the quality and resolution of the electronically processed images obtained during MRI examinations of the circulation and/or circulation targeted organs. The compositions are formulated to protect the particles of the contrast agents from early removal by the reticulo-endothelial (RES) system of the liver and the spleen, so that they will stay in the circulation for a time sufficient to properly image the blood vessels and to be transported to selected organs. MRI imaging of the circulation and of targeted organs can strongly assist in diagnosing possible ailments in human and animal patients.
摘要翻译：本发明涉及包含悬浮或分散在生理上可接受的水性液体载体中的混合胶束形式的生理上可接受的两亲性有机底物材料的磁响应物质的NMR成像对比剂组合物。该组合物特别适用于血液池的诊断研究。本发明还涉及混合胶束的制备，以及含有混合胶束作为MRI目的的造影剂的可注射组合物。一旦注射，组合物的混合胶束表现为成像对比增强剂，例如，它们将提高在循环和/或循环目标器官的MRI检查期间获得的电子处理图像的质量和分辨率。配制组合物以保护造影剂的颗粒免于肝脏和脾脏的网状内皮（RES）系统的早期去除，使得它们将停留在循环中足以适当地使血管成像的时间，被运送到选定的器官。循环和目标器官的MRI成像可以有力地帮助诊断人类和动物患者的可能的疾病。

3. 发明申请

US20070196284A1 Liposomal assembly for therapeutic and/or diagnostic use 有权
标题翻译：用于治疗和/或诊断用途的脂质体组装
公开(公告)号：US20070196284A1
公开(公告)日：2007-08-23
申请号：US11596447
申请日：2005-05-31
申请人： Herve Tournier , Roland Hyacinthe , Michel Schneider
发明人： Herve Tournier , Roland Hyacinthe , Michel Schneider
IPC分类号： A61K49/10 , A61K9/127
CPC分类号： A61K9/1075 , A61K9/1271 , A61K48/0091 , A61K49/1812 , C12N15/88 , Y10S977/907 , Y10T428/2982
摘要： Composition for diagnostic or therapeutic use which comprises an assembly comprising an active agent. The assembly comprises a liposome and a plurality of micellar components associated thereto, said micellar components being associated to the outer surface of the envelope of said liposome through a substantially electrostatic interaction. When an active compound is incorporated into the micelles, a substantial amount of said active compound can be linked to a singe liposome. Furthermore, the presence of the outer micellar layer allows to increase the residence time of said liposome in the blood stream.
摘要翻译：用于诊断或治疗用途的组合物，其包含包含活性剂的组合物。组合物包含脂质体和与其相关联的多个胶束组分，所述胶束组分通过基本静电相互作用与所述脂质体的包膜的外表面相关联。当活性化合物掺入胶束中时，大量的所述活性化合物可以连接到单个脂质体。此外，外胶束层的存在允许增加所述脂质体在血流中的停留时间。

4. 发明授权

US5688490A Mucoadhesive compositions for increasing the ultrasonic image contrast of the digestive tract 失效
标题翻译：用于增加消化道超声波图像对比度的粘膜组合物
公开(公告)号：US5688490A
公开(公告)日：1997-11-18
申请号：US598226
申请日：1996-02-07
申请人： Herve Tournier , Roland Hyacinthe , Friedrich Cavagna
发明人： Herve Tournier , Roland Hyacinthe , Friedrich Cavagna
IPC分类号： A61K47/26 , A61K49/00 , A61K49/18 , A61K49/22 , G01R33/28 , A61B8/13
CPC分类号： G01R33/5601 , A61K49/1845 , A61K49/1854 , A61K49/1863 , A61K49/1893 , A61K49/223 , A61K49/226 , Y10S514/836 , Y10T436/24
摘要： Suspensions of either echogenic or magnetic particles in aqueous bioadhesive carriers effectively improve imaging by echography, respectively NMRI, of the digestive tract. Affinity of the compositions for the gastric mucosa can be adapted to the needs by appropriately selecting the carrier in function to inherent bioadhesive capacity: this technique leads to improved visualization of selected portions of the lumen.
摘要翻译：在水性生物粘附载体中的回声或磁性颗粒的悬浮液通过回波图（分别为消化道的NMRI）有效地改善成像。用于胃粘膜的组合物的亲和力可以通过适当地选择载体的功能来适应于固有的生物粘附能力的需要：该技术导致改变的管腔选定部分的可视化。

5. 发明授权

US5370901A Compositions for increasing the image contrast in diagnostic investigations of the digestive tract of patients 失效
标题翻译：用于增加患者消化道诊断调查中图像对比度的组合
公开(公告)号：US5370901A
公开(公告)日：1994-12-06
申请号：US824311
申请日：1992-01-23
申请人： Herve Tournier , Roland Hyacinthe , Friedrich Cavagna
发明人： Herve Tournier , Roland Hyacinthe , Friedrich Cavagna
IPC分类号： A61K47/26 , A61K49/00 , A61K49/18 , A61K49/22 , G01R33/28 , A61K9/16 , A61B8/12
CPC分类号： G01R33/5601 , A61K49/1845 , A61K49/1854 , A61K49/1863 , A61K49/1893 , A61K49/223 , A61K49/226 , Y10S514/836 , Y10T436/24
摘要： Method of making an ingestible composition useful as a contrast enhancing agent in ultrasonic imaging of the digestive tract of humans and animals, wherein the composition has microballoons as contrast enhancing particles bound to an organic carrier phase, which when hydrated has an adhesive affinity for the gastrointestinal mucosa.Method includes grafting a silane coupler having at least two reactive functions to the microballoons through one of the reactive functions and binding the grafted microballoons to the carrier phase through another reactive function.
摘要翻译：制备可用作对比增强剂的可摄取组合物在人和动物消化道超声成像中的方法，其中所述组合物具有微球作为与有机载体相结合的对比增强颗粒，当与水合物具有对胃肠道的粘合亲和力时粘膜方法包括通过反应性功能之一将具有至少两个反应性功能的硅烷偶联剂接枝到微球上，并通过另一个反应性官能将接枝的微球结合到载体相上。

6. 发明授权

US07749485B2 Liposomal assembly for therapeutic and/or diagnostic use 有权
标题翻译：用于治疗和/或诊断用途的脂质体组装
公开(公告)号：US07749485B2
公开(公告)日：2010-07-06
申请号：US11596447
申请日：2005-05-31
申请人： Herve Tournier , Roland Hyacinthe , Michel Schneider
发明人： Herve Tournier , Roland Hyacinthe , Michel Schneider
IPC分类号： A61K51/00 , A61M36/14 , B32B5/16 , B01F3/00
CPC分类号： A61K9/1075 , A61K9/1271 , A61K48/0091 , A61K49/1812 , C12N15/88 , Y10S977/907 , Y10T428/2982
摘要： Composition for diagnostic or therapeutic use which comprises an assembly comprising an active agent. The assembly comprises a liposome and a plurality of micellar components associated thereto, said micellar components being associated to the outer surface of the envelope of said liposome through a substantially electrostatic interaction, When an active compound is incorporated into the micelles, a substantial amount of said active compound can be linked to a singe liposome. Furthermore, the presence of the outer micellar layer allows to increase the residence time of said liposome in the blood stream.
摘要翻译：用于诊断或治疗用途的组合物，其包含包含活性剂的组合物。组合物包含脂质体和与其相关联的多个胶束组分，所述胶束组分通过基本上静电的相互作用与所述脂质体的外壳的外表面结合。当将活性化合物并入胶束中时，大量的所述活性化合物可以连接到单个脂质体。此外，外胶束层的存在允许增加所述脂质体在血流中的停留时间。

7. 发明授权

US5545395A Method of imaging using encapsulated magnetite particles 失效
标题翻译：使用封装的磁铁矿颗粒成像的方法
公开(公告)号：US5545395A
公开(公告)日：1996-08-13
申请号：US421330
申请日：1995-04-13
申请人： Herve Tournier , Roland Hyacinthe , Michel Schneider
发明人： Herve Tournier , Roland Hyacinthe , Michel Schneider
IPC分类号： A61K9/127 , A61B5/055 , A61K20060101 , A61K49/00 , A61K49/18
CPC分类号： A61K49/1806 , A61K49/1839 , Y10S977/838 , Y10S977/904 , Y10S977/905 , Y10S977/927 , Y10S977/96 , Y10T428/2991 , Y10T428/2998 , Y10T436/24
摘要： Magnetite particles suitable for injection into the blood stream of patients having enhanced resistance against agglomeration and uptake by the RES of the liver and spleen. The particles essentially consist of an iron oxide core and a phosphoric acid mono alkyl or alkenyl ester or glycerophospholipid/surfactant three dimensional shell surrounding the core. The core and the monoester or a micellar glycerophospholipid form an urchin-like structure which is further interlaced or intertwined with a non-ionic surfactant to produce a protective three dimensional shell which renders particles almost undetectable by the macrophages. Particles prepared according to the invention are kept in the blood circulation for long periods and represent excellent long lasting blood pool agents. Key components in the shell are (a) a polybasic mineral-organic species such as glycero phosphatidic acid in micellar form and (b) a block copolymer having successive hydrophilic and hydrophobic segments.
摘要翻译：适合于注射到患有肝脏和脾脏的RES的聚集和摄取的抗性的患者血液中的磁铁矿颗粒。颗粒基本上由氧化铁芯和磷酸单烷基或链烯基酯或包含核心的甘油磷脂/表面活性剂三维壳组成。核心和单酯或胶束甘油磷脂形成海胆样结构，其进一步与非离子表面活性剂交织或交织在一起，以产生保护性三维壳，其使颗粒几乎不被巨噬细胞检测到。根据本发明制备的颗粒长时间保持在血液循环中并且代表优异的持久的血液池剂。壳中的关键组分是（a）多元矿物有机物质，例如胶束形式的甘油磷脂酸，和（b）具有连续亲水和疏水链段的嵌段共聚物。

8. 发明授权

US5792445A Polymers and copolymers of acrylic acid MRI of the digestive tract of patients 失效
标题翻译：丙烯酸聚合物和共聚物患者消化道MRI
公开(公告)号：US5792445A
公开(公告)日：1998-08-11
申请号：US598225
申请日：1996-02-07
申请人： Herve Tournier , Roland Hyacinthe , Friedrich Cavagna
发明人： Herve Tournier , Roland Hyacinthe , Friedrich Cavagna
IPC分类号： A61K47/26 , A61K49/00 , A61K49/18 , A61K49/22 , G01R33/28 , A61B5/055
CPC分类号： G01R33/5601 , A61K49/1845 , A61K49/1854 , A61K49/1863 , A61K49/1893 , A61K49/223 , A61K49/226 , Y10S514/836 , Y10T436/24
摘要： Suspensions of either echogenic or magnetic particles in aqueous bioadhesive carriers effectively improve imaging by echography, respectively NMRI, of the digestive tract. Affinity of the compositions for the gastric mucosa can be adapted to the needs by appropriately selecting the carrier in function to inherent bioadhesive capacity: this technique leads to improved visualization of selected portions of the lumen.
摘要翻译：在水性生物粘附载体中的回声或磁性颗粒的悬浮液通过回波图（分别为消化道的NMRI）有效地改善成像。用于胃粘膜的组合物的亲和力可以通过适当地选择载体的功能来适应于固有的生物粘附能力的需要：该技术导致改变的管腔选定部分的可视化。

9. 发明授权

US5653959A Compositions for increasing the image contrast in diagnostic investigations of the digestive tract of patients 失效
标题翻译：用于增加患者消化道诊断调查中图像对比度的组合
公开(公告)号：US5653959A
公开(公告)日：1997-08-05
申请号：US257510
申请日：1994-06-08
申请人： Herve Tournier , Roland Hyacinthe , Friedrich Cavagna
发明人： Herve Tournier , Roland Hyacinthe , Friedrich Cavagna
IPC分类号： A61K47/26 , A61K49/00 , A61K49/18 , A61K49/22 , G01R33/28 , A61B5/055 , G01N24/00
CPC分类号： G01R33/5601 , A61K49/1845 , A61K49/1854 , A61K49/1863 , A61K49/1893 , A61K49/223 , A61K49/226 , Y10S514/836 , Y10T436/24
摘要： Suspensions of either echogenic or magnetic particles in aqueous bioadhesive carriers effectively improve imaging by echography, respectively NMRI, of the digestive tract. Affinity of the compositions for the gastric mucosa can be adapted to the needs by appropriately selecting the carrier in function to inherent bioadhesive capacity: this technique leads to improved visualization of selected portions of the lumen.
摘要翻译：在水性生物粘附载体中的回声或磁性颗粒的悬浮液通过回波图（分别为消化道的NMRI）有效地改善成像。用于胃粘膜的组合物的亲和力可以通过适当地选择载体的功能来适应于固有的生物粘附能力的需要：该技术导致改变的管腔选定部分的可视化。

10. 发明授权

US5587199A Process of preparing particles for NMR imaging 失效
标题翻译：制备核磁共振成像颗粒的方法
公开(公告)号：US5587199A
公开(公告)日：1996-12-24
申请号：US421329
申请日：1995-04-13
申请人： Herve Tournier , Roland Hyacinthe , Michel Schneider
发明人： Herve Tournier , Roland Hyacinthe , Michel Schneider
IPC分类号： A61K9/127 , A61B5/055 , A61K20060101 , A61K49/00 , A61K49/18 , B05D7/00 , B05D3/12 , B06B1/00 , B32B9/00
CPC分类号： A61K49/1806 , A61K49/1839 , Y10S977/838 , Y10S977/904 , Y10S977/905 , Y10S977/927 , Y10S977/96 , Y10T428/2991 , Y10T428/2998 , Y10T436/24
摘要： Magnetite particles suitable for injection into the blood stream of patients having enhanced resistance against agglomeration and uptake by the RES of the liver and spleen. The particles essentially consist of an iron oxide core and a phosphoric acid mono alkyl or alkenyl ester or glycerophospholipid/surfactant three dimensional shell surrounding the core. The core and the monoester or a micellar glycerophospholipid form an urchin-like structure which is further interlaced or intertwined with a non-ionic surfactant to produce a protective three dimensional shell which renders particles almost undetectable by the macrophages. Particles prepared according to the invention are kept in the blood circulation for long periods and represent excellent long lasting blood pool agents. Key components in the shell are (a) a polybasic mineral-organic species such as glycero phosphatidic acid in micellar form and (b) a block copolymer having successive hydrophilic and hydrophobic segments.
摘要翻译：适合于注射到患有肝脏和脾脏的RES的聚集和摄取的抗性的患者血液中的磁铁矿颗粒。颗粒基本上由氧化铁芯和磷酸单烷基或链烯基酯或包含核心的甘油磷脂/表面活性剂三维壳组成。核心和单酯或胶束甘油磷脂形成海胆样结构，其进一步与非离子表面活性剂交织或交织在一起，以产生保护性三维壳，其使颗粒几乎不被巨噬细胞检测到。根据本发明制备的颗粒长时间保持在血液循环中并且代表优异的持久的血液池剂。壳中的关键组分是（a）多元矿物有机物质，例如胶束形式的甘油磷脂酸，和（b）具有连续亲水和疏水链段的嵌段共聚物。

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