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31. 发明授权

US5686060A Stable microbubble suspensions comprising saturated phospholipids for ultrasound echography 失效
标题翻译：稳定的微泡悬浮液，包括用于超声回波的饱和磷脂
公开(公告)号：US5686060A
公开(公告)日：1997-11-11
申请号：US420677
申请日：1995-04-12
申请人： Michel Schneider , Jean Brochot , Jerome Puginier , Feng Yan
发明人： Michel Schneider , Jean Brochot , Jerome Puginier , Feng Yan
IPC分类号： A61K47/24 , A61B8/08 , A61B8/12 , A61B8/13 , A61K9/127 , A61K49/00 , A61K49/22 , B01F3/04 , B01J13/02
CPC分类号： A61K49/225 , A61K49/223
摘要： Disclosed are injectable suspensions of gas filled microbubbles in an aqueous carrier liquid usable as contrast agents in ultrasonic echography. The suspensions comprise amphipathic compounds of which at least one may be a laminarized phospholipid as a stabilizer of the microbubbles against collapse with time and pressure. The concentration of phospholipids in the carrier liquid is below 0.01% wt but is at least equal to or above that at which phospholipid molecules are present solely at the gas microbubble-liquid interface. Also disclosed is a method of preparation of the stable suspensions of air or gas filled microbubbles.
摘要翻译：公开了在超声波回波成像中可用作造影剂的水性载体液体中的气体填充微泡的可注射悬浮液。悬浮液包含两亲性化合物，其中至少一种可以是层状磷脂作为微泡的稳定剂，以防止随时间和压力而塌陷。载体液体中磷脂的浓度低于0.01％wt，但至少等于或高于磷脂分子仅存在于气体微泡液界面的浓度。还公开了制备空气或气体填充的微泡的稳定悬浮液的方法。

32. 发明授权

US5597549A Stable microbubble suspensions as enhancement agents for ultrasound echography 失效
标题翻译：稳定的微泡悬浮液作为超声波回波成像的增强剂
公开(公告)号：US5597549A
公开(公告)日：1997-01-28
申请号：US414718
申请日：1995-03-31
申请人： Michel Schneider , Jean Brochot , Jerome Puginier , Feng Yan
发明人： Michel Schneider , Jean Brochot , Jerome Puginier , Feng Yan
IPC分类号： A61K47/24 , A61B8/08 , A61B8/12 , A61B8/13 , A61K9/127 , A61K49/00 , A61K49/22 , B01F3/04 , B01J13/02
CPC分类号： A61K49/225 , A61K49/223
摘要： Disclosed are injectable suspensions of gas filled microbubbles in an aqueous carrier liquid usable as contrast agents in ultrasonic echography. The suspensions comprise amphipathic compounds of which at least one may be a laminarized phospholipid as a stabilizer of the microbubbles against collapse with time and pressure. The concentration of phospholipids in the carrier liquid is below 0.01% wt but is at least equal to or above that at which phospholipid molecules are present solely at the gas microbubble-liquid interface. Also disclosed is a method of preparation of the stable suspensions of air or gas filled microbubbles.
摘要翻译：公开了在超声波回波成像中可用作造影剂的水性载体液体中的气体填充微泡的可注射悬浮液。悬浮液包含两亲性化合物，其中至少一种可以是层状磷脂作为微泡的稳定剂，以防止随时间和压力而塌陷。载体液体中磷脂的浓度低于0.01％wt，但至少等于或高于磷脂分子仅存在于气体微泡液界面的浓度。还公开了制备空气或气体填充的微泡的稳定悬浮液的方法。

33. 发明授权

US09750821B2 Gas-filled microvesicle assembly for contrast imaging 有权
公开(公告)号：US09750821B2
公开(公告)日：2017-09-05
申请号：US10584327
申请日：2004-12-21
申请人： Michel Schneider , Philippe Bussat , Feng Yan , Anne Senente
发明人： Michel Schneider , Philippe Bussat , Feng Yan , Anne Senente
IPC分类号： A61K47/48 , A61K41/00 , A61K49/22
CPC分类号： A61K47/6925 , A61K41/0028 , A61K49/225
摘要： Assembly comprising a gas-filled microvesicle and a structural entity which is capable to associate through an electrostatic interaction to the outer surface of said microvesicle (microvesicle associated component—MAC), thereby modifying the physico-chemical properties thereof. Said MAC may optionally comprise a targeting ligand, a bioactive agent, a diagnostic agent or any combination thereof. The assembly of the invention can be formed from gasfilled microbubbles or microballoons and a MAC having a diameter of less than 100 pm, in particular a micelle and is used as an active component in diagnostically and/or therapeutically active formulations, in particular for enhancing the imaging in the field of ultrasound contrast imaging, including targeted ultrasound imaging, ultrasound-mediated drug delivery and other imaging techniques such as molecular resonance imaging (MRI) or nuclear imaging.

34. 发明申请

US20070071685A1 Gas-filled microvesicle assembly for contrast imaging 有权
标题翻译：气体填充微泡组件，用于对比成像
公开(公告)号：US20070071685A1
公开(公告)日：2007-03-29
申请号：US10584327
申请日：2004-12-21
申请人： Michel Schneider , Philippe Bussat , Feng Yan , Anne Senente
发明人： Michel Schneider , Philippe Bussat , Feng Yan , Anne Senente
IPC分类号： A61K49/22
CPC分类号： A61K47/6925 , A61K41/0028 , A61K49/225
摘要： Assembly comprising a gas-filled microvesicle and a structural entity which is capable to associate through an electrostatic interaction to the outer surface of said microvesicle (microvesicle associated component—MAC), thereby modifying the physico-chemical properties thereof. Said MAC may optionally comprise a targeting ligand, a bioactive agent, a diagnostic agent or any combination thereof. The assembly of the invention can be formed from gasfilled microbubbles or microballoons and a MAC having a diameter of less than 100 pm, in particular a micelle and is used as an active component in diagnostically and/or therapeutically active formulations, in particular for enhancing the imaging in the field of ultrasound contrast imaging, including targeted ultrasound imaging, ultrasound-mediated drug delivery and other imaging techniques such as molecular resonance imaging (MRI) or nuclear imaging.
摘要翻译：组件包括充气微泡和结构实体，其能够通过静电相互作用与所述微囊体（微泡相关组分-MAC）的外表面缔合，从而改变其物理化学性质。所述MAC可以任选地包含靶向配体，生物活性剂，诊断剂或其任何组合。本发明的组件可以由气体填充的微泡或微球和直径小于100μm的MAC，特别是胶束形成，并且用作诊断和/或治疗活性制剂中的活性成分，特别是用于增强在超声对比成像领域的成像，包括靶向超声成像，超声介导的药物递送和其他成像技术如分子共振成像（MRI）或核成像。

35. 发明授权

US09364569B2 Ultrasound contrast agents and process for the preparation thereof 有权
公开(公告)号：US09364569B2
公开(公告)日：2016-06-14
申请号：US10544123
申请日：2004-02-03
申请人： Michel Schneider , Philippe Bussat , Feng Yan , Christian Guillot
发明人： Michel Schneider , Philippe Bussat , Feng Yan , Christian Guillot
IPC分类号： A61K49/22
CPC分类号： A61K49/223
摘要： Method for preparing a lyophilized matrix and, upon reconstitution of the same, a respective injectable contrast agent comprising a liquid aqueous suspension of gas-filled microbubbles stabilized predominantly by a phospholipid. The method comprises preparing an emulsion from an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and subsequently reconstituted in an aqueous suspension of gas-filled microbubbles. The method allows to obtain suspensions comprising microbubbles having a relatively small diameter and a narrow size distribution.

36. 发明申请

US20110150778A1 Assembly of Gas-Filled Microvesicle With Active Component For Contrast Imaging 审中-公开
标题翻译：装配用于对比成像的活性成分的气体填充微囊
公开(公告)号：US20110150778A1
公开(公告)日：2011-06-23
申请号：US13018290
申请日：2011-01-31
申请人： Michel Schneider , Philippe Bussat , Feng Yan , Anne Senente
发明人： Michel Schneider , Philippe Bussat , Feng Yan , Anne Senente
IPC分类号： A61B5/055 , A61B8/00 , A61K39/395 , A61K9/00 , A61K38/00 , A61K38/14 , A61K31/70 , A61K31/715 , A61K31/56 , A61K38/22 , A61K31/7088 , A61P43/00
CPC分类号： A61K41/0028 , A61K47/6925 , A61K49/225
摘要： Assembly comprising a gas-filled microvesicle and a structural entity which is capable to associate through an electrostatic interaction to the outer surface of said microvesicle (microvesicle associated component—MAC), thereby modifying the physico-chemical properties thereof. Said MAC comprises a targeting ligand a diagnostic agent or any combination thereof. Optionally a bioactive agent can further be associated to the MAC. The assembly of the invention can be formed from gas-filled microbubbles or microballoons and a MAC having preferably nanometric dimensions, e.g. a micelle, and is used as an active component in diagnostically and/or therapeutically active formulations, in particular for enhancing the imaging in the field of ultrasound contrast imaging, including targeted ultrasound imaging, ultrasound-mediated drug delivery and other imaging techniques such as molecular resonance imaging (MRI) or nuclear imaging.
摘要翻译：组件包括充气微泡和结构实体，其能够通过静电相互作用与所述微囊体（微泡相关组分-MAC）的外表面缔合，从而改变其物理化学性质。所述MAC包含靶向配体，诊断剂或其任何组合。可选地，生物活性剂可以进一步与MAC相关联。本发明的组件可以由气体填充的微泡或微球和具有优选纳米尺度的MAC形成，例如，胶束，并且用作诊断和/或治疗活性制剂中的活性成分，特别是用于增强超声造影成像领域的成像，包括靶向超声成像，超声介导的药物递送和其他成像技术如分子共振成像（MRI）或核成像。

37. 发明申请

US20060034770A1 Ultrasound contrast agents and process for the preparation thereof 审中-公开
标题翻译：超声造影剂及其制备方法
公开(公告)号：US20060034770A1
公开(公告)日：2006-02-16
申请号：US11202008
申请日：2005-08-11
申请人： Michel Schneider , Philippe Bussat , Feng Yan , Christian Guillot
发明人： Michel Schneider , Philippe Bussat , Feng Yan , Christian Guillot
IPC分类号： A61K49/22
CPC分类号： A61K49/223
摘要： Injectable aqueous suspension of microbubbles filled with a biocompatible gas and a method of preparation thereof. At least 10% of the total volume of gas contained in the microbubbles is contained in microbububbles with a diameter of 1.5 μm or less. The microbubbles can be obtained by preparing an emulsion comprising an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and then reconstituted in an aqueous suspension of gas-filled microbubbles.
摘要翻译：填充有生物相容性气体的微泡的可注射水性悬浮液及其制备方法。包含在微泡中的气体的总体积的至少10％包含在直径为1.5μm或更小的微泡中。微泡可以通过制备包含水性介质，磷脂和与水不混溶的有机溶剂的乳液来获得。然后将乳液冷冻干燥，然后在气体填充的微泡的水性悬浮液中重构。

38. 发明申请

US20110236320A1 Ultrasound Contrast Agents And Process For The Preparation Thereof 审中-公开
标题翻译：超声对比剂及其制备方法
公开(公告)号：US20110236320A1
公开(公告)日：2011-09-29
申请号：US13039838
申请日：2011-03-03
申请人： Michel Schneider , Philippe Bussat , Feng Yan , Christian Guillot
发明人： Michel Schneider , Philippe Bussat , Feng Yan , Christian Guillot
IPC分类号： A61B8/00 , A61K9/00 , A61P43/00
CPC分类号： A61K49/223
摘要： Injectable aqueous suspension of microbubbles filled with a biocompatible gas and a method of preparation thereof. At least 10% of the total volume of gas contained in the microbubbles is contained in microbubbles with a diameter of 1.5 μm or less. The microbubbles can be obtained by preparing an emulsion comprising an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and then reconstituted in an aqueous suspension of gas-filled microbubbles.
摘要翻译：填充有生物相容性气体的微泡的可注射水性悬浮液及其制备方法。包含在微泡中的气体总体积的至少10％被包含在直径为1.5μm或更小的微泡中。微泡可以通过制备包含水性介质，磷脂和与水不混溶的有机溶剂的乳液来获得。然后将乳液冷冻干燥，然后在气体填充的微泡的水性悬浮液中重构。

39. 发明申请

US20070081946A1 Assembly of gas-filled microvesicle with active component for contrast imaging 审中-公开
标题翻译：装有气体填充微泡与活性成分进行对比成像
公开(公告)号：US20070081946A1
公开(公告)日：2007-04-12
申请号：US10584382
申请日：2004-12-21
申请人： Michel Schneider , Philippe Bussat , Feng Yan , Anne Senente
发明人： Michel Schneider , Philippe Bussat , Feng Yan , Anne Senente
IPC分类号： A61K49/22
CPC分类号： A61K41/0028 , A61K47/6925 , A61K49/225
摘要： Assembly comprising a gas-filled microvesicle and a structural entity which is capable to associate through an electrostatic interaction to the outer surface of said microvesicle (microvesicle associated component—MAC), thereby modifying the physico-chemical properties thereof. Said MAC comprises a targeting ligand a diagnostic agent or any combination thereof. Optionally a bioactive agent can further be associated to the MAC. The assembly of the invention can be formed from gas-filled microbubbles or microballoons and a MAC having preferably nanometric dimensions, e.g. a micelle, and is used as an active component in diagnostically and/or therapeutically active formulations, in particular for enhancing the imaging in the field of ultrasound contrast imaging, including targeted ultrasound imaging, ultrasound-mediated drug delivery and and other imaging techniques such as molecular resonance imaging (MRI) or nuclear imaging.
摘要翻译：组件包括充气微泡和结构实体，其能够通过静电相互作用与所述微囊体（微泡相关组分-MAC）的外表面缔合，从而改变其物理化学性质。所述MAC包含靶向配体，诊断剂或其任何组合。可选地，生物活性剂可以进一步与MAC相关联。本发明的组件可以由气体填充的微泡或微球和具有优选纳米尺度的MAC形成，例如，胶束，并且用作诊断和/或治疗活性制剂中的活性成分，特别是用于增强超声对比成像领域的成像，包括靶向超声成像，超声介导的药物递送和其它成像技术，例如分子共振成像（MRI）或核成像。

40. 发明申请

US20060051297A1 Ultrasound contrast agents and process for the preparation thereof 有权
标题翻译：超声造影剂及其制备方法
公开(公告)号：US20060051297A1
公开(公告)日：2006-03-09
申请号：US10544123
申请日：2004-02-03
申请人： Michel Schneider , Philippe Bussat , Feng Yan , Christian Guillot
发明人： Michel Schneider , Philippe Bussat , Feng Yan , Christian Guillot
IPC分类号： A61K49/22
CPC分类号： A61K49/223
摘要： Method for preparing a lyophilized matrix and, upon reconstitution of the same, a respective injectable contrast agent comprising a liquid aqueous suspension of gas-filled microbubbles stabilized predominantly by a phospholipid. The method comprises preparing an emulsion from an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and subsequently reconstituted in an aqueous suspension of gas-filled microbubbles. The method allows to obtain suspensions comprising microbubbles having a relatively small diameter and a narrow size distribution.
摘要翻译：制备冻干基质的方法，并且在重构相应的可注射造影剂时，其包含主要由磷脂稳定的充气微泡的液体水性悬浮液。该方法包括从水性介质，磷脂和与水不混溶的有机溶剂中制备乳液。然后将乳液冷冻干燥，随后在气体填充的微泡的水性悬浮液中重构。该方法允许获得包含具有相对小直径和窄尺寸分布的微泡的悬浮液。

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