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公开(公告)号：US06726650B2
公开(公告)日：2004-04-27
申请号：US09204067
申请日：1998-12-03
申请人： Michel Schneider , Christophe Golay , Laurent Jakob , Jean Brochot , Feng Yan , Christian Mathieu
发明人： Michel Schneider , Christophe Golay , Laurent Jakob , Jean Brochot , Feng Yan , Christian Mathieu
IPC分类号： A61M3700
CPC分类号： A61M5/1456 , A61B2017/22008 , A61B2090/3925 , A61B2090/3933 , A61M5/007 , A61M2205/6072 , B01F9/0016 , B01F11/0002 , B01F2003/0035
摘要： A power assisted method and injector device for controllably delivering to patients a dispersion medicament or diagnostically active agent, the homogeneity of which is preserved throughout delivery. Diagnostically active agents disclosed are gas microbubble suspensions useful in ultrasonic diagnostic imaging and liposomal formulations in which liposome vesicles are loaded with iodinated compounds.
摘要翻译： 一种功率辅助方法和注射器装置，用于可控地向患者输送分散药物或诊断活性剂，其均匀性在整个递送期间保留。 所公开的诊断活性剂是用于超声诊断成像的气体微泡悬浮液和其中脂质体囊泡装载碘化化合物的脂质体制剂。
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公开(公告)号：US5961956A
公开(公告)日：1999-10-05
申请号：US944408
申请日：1997-10-06
申请人： Feng Yan , Michel Schneider , Jean Brochot
发明人： Feng Yan , Michel Schneider , Jean Brochot
CPC分类号： A61K49/223
摘要： Disclosed are suspensions of gas microbubbles immobilised within a frozen aqueous carrier liquid comprising usual additives and stabilisers, in which the carrier liquid is a physiologically acceptable, the immobilised gas microbubbles are microbubbles bound by an evanescent envelope or a tangible membrane. The suspensions, when in liquid form, are injectable and useful as a contrast agents in ultrasonic imaging of blood pool and tissue of living beings. The gas microbubbles are immobilised within the carrier by freezing a suspension of microbubbles with average sizes below 50 .mu.m, preferably below 10 .mu.m and more preferably between 2 .mu.m and 8 .mu.m, to a temperature between -1.degree. C. and -76.degree. C. and maintaining this temperature for prolonged periods of time. The microbubbles may be stabilised by a surfactant such as a lamellar phospholipid or may comprise a membrane made of synthetic or natural polymer or protein. A method of cold storage of microbubble suspensions as well as their use is also disclosed.
摘要翻译： 公开了固定在包含通常的添加剂和稳定剂的冷冻含水载体液体中的气体微泡的悬浮液，其中载体液体是生理上可接受的，固定化气体微泡是由ev逝包膜或有形膜结合的微泡。 当液体形式时，悬浮液是可注射的，并且可用作血液池和生物组织的超声成像中的造影剂。 将气体微泡固定在载体中，将平均尺寸低于50μm，优选低于10μm，更优选在2μm和8μm之间的微泡悬浮液冷冻至-1℃至-1℃的温度， 76℃，并保持该温度较长时间。 微泡可以通过表面活性剂如片状磷脂来稳定，或者可以包含由合成或天然聚合物或蛋白质制成的膜。 还公开了微泡悬浮液的冷藏方法及其用途。
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63.发明授权Gas mixtures useful as ultrasound contrast media contrast agents containing the media and method 失效用作含有介质和方法的超声造影剂造影剂的气体混合物
公开(公告)号：US5846518A
公开(公告)日：1998-12-08
申请号：US848912
申请日：1997-05-01
申请人： Feng Yan , Michel Schneider , Jean Brochot
发明人： Feng Yan , Michel Schneider , Jean Brochot
CPC分类号： A61K49/223 , A61K49/225
摘要： The invention relates to injectable media for ultrasonic echography in the form of microbubbles or microballoons comprising at least two biocompatible substances A and B (gaseous at the body temperature) forming a mixture which when in suspension with usual surfactants, additives and stabilisers provides useful ultrasound contrast agents. At least one of the components (B) in the mixture is a gas whose molecular weight is greater than 80 daltons and whose solubility in water is below 0.0283 ml per ml of water at standard conditions. The presence of the first component (B) in the contrast medium may vary between 0.5 and 41 volume percent. The other component (A) of the ultrasound contrast media is a gas or a mixture of gases whose molecular weight is below 80 daltons. The second component is present in a proportion of between 59-99.5% by vol., and is preferably chosen from oxygen, air, nitrogen, carbon dioxide or mixtures thereof. Gas mixtures described are found to be very effective as ultrasound contrast media. The invention also comprises a method of making the ultrasound contrast medium, the contrast agent and the ultrasound agent kit.
摘要翻译： 本发明涉及以微泡或微球形式的超声波回波成像的可注射介质，其包含至少两种生物相容性物质A和B（在体温下为气体）形成混合物，当与通常的表面活性剂悬浮时，添加剂和稳定剂提供有用的超声对比 代理商 混合物中组分（B）中的至少一种是分子量大于80道尔顿且在标准条件下其在水中的溶解度低于0.0283ml / ml水的气体。 造影剂中第一组分（B）的存在可以在0.5和41体积％之间变化。 超声造影剂的另一组分（A）是分子量低于80道尔顿的气体或气体混合物。 第二组分以59-99.5体积％的比例存在，优选选自氧气，空气，氮气，二氧化碳或其混合物。 发现所描述的气体混合物作为超声波造影剂非常有效。 本发明还包括制造超声造影剂，造影剂和超声剂试剂盒的方法。
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64.发明授权Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method 失效用作超声波造影剂的气体混合物，含有介质和方法的造影剂
公开(公告)号：US5556610A
公开(公告)日：1996-09-17
申请号：US352108
申请日：1994-11-30
申请人： Feng Yan , Michel Schneider , Jean Brochot
发明人： Feng Yan , Michel Schneider , Jean Brochot
CPC分类号： A61K49/225 , A61K49/223
摘要： The invention relates to injectable media for ultrasonic echography in the form of microbubbles or microballoons comprising at least two biocompatible substances A and B (gaseous at the body temperature) forming a mixture which when in suspension with usual surfactants, additives and stabilisers provides useful ultrasound contrast agents. At least one of the components (B) in the mixture is a gas whose molecular weight is greater than 80 daltons and whose solubility in water is below 0.0283 ml per ml of water at standard conditions. The presence of the first component (B) in the contrast medium may vary between 0.15 and 41 volume percent. The other component (A) of the ultrasound contrast media is a gas or a mixture of gases whose molecular weight is below 80 daltons. The second component is present in a proportion of between 59-99.5% by vol., and is preferably chosen from oxygen, air, nitrogen, carbon dioxide or mixtures thereof. Gas mixtures described are found to be very effective as ultrasound contrast media. The invention also comprises a method of making the ultrasound contrast medium, the contrast agent and the ultrasound agent kit.
摘要翻译： 本发明涉及以微泡或微球形式的超声波回波成像的可注射介质，其包含至少两种生物相容性物质A和B（在体温下为气体）形成混合物，当与通常的表面活性剂悬浮时，添加剂和稳定剂提供有用的超声对比 代理商 混合物中组分（B）中的至少一种是分子量大于80道尔顿且在标准条件下其在水中的溶解度低于0.0283ml / ml水的气体。 造影剂中第一组分（B）的存在可以在0.15和41体积％之间变化。 超声造影剂的另一组分（A）是分子量低于80道尔顿的气体或气体混合物。 第二组分以59-99.5体积％的比例存在，优选选自氧气，空气，氮气，二氧化碳或其混合物。 发现所描述的气体混合物作为超声波造影剂非常有效。 本发明还包括制造超声造影剂，造影剂和超声剂试剂盒的方法。
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65.发明授权Stable microbubble suspensions as enhancement agents for ultrasonic echography 有权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：US06187288B1
公开(公告)日：2001-02-13
申请号：US09151651
申请日：1998-09-11
申请人： Michel Schneider , Jean Brochot , Jérôme Puginier , Feng Yan
发明人： Michel Schneider , Jean Brochot , Jérôme Puginier , Feng Yan
IPC分类号： A61B813
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。
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公开(公告)号：US20070196284A1
公开(公告)日：2007-08-23
申请号：US11596447
申请日：2005-05-31
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。
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67.发明申请Reconstitutable formulation and aqueous suspension of gas-filled microvesicles for diagnostic imaging 审中-公开用于诊断成像的气体填充微泡的可重构制剂和水悬浮液公开(公告)号：US20050025710A1
公开(公告)日：2005-02-03
申请号：US10630375
申请日：2003-07-29
申请人： Michel Schneider , Yan Feng , Jean Brochot , David Lazurus
发明人： Michel Schneider , Yan Feng , Jean Brochot , David Lazurus
CPC分类号： A61K49/1815 , A61K49/225
摘要： The invention relates to a formulation comprising a dry material (e.g. lyophilised or spray dried) comprising at least one film forming surfactant and a gas or a gas mixture usable in diagnostic imaging, to a process for the preparation thereof and to a suspension obtainable by reconstituting said formulation with an aqueous carrier for use in contrast imaging. The invention also relates to a container comprising the dry material in contact with a gas. The gas associated with the dry material is at a pressure lower than the atmospheric pressure.
摘要翻译： 本发明涉及包含干物质（例如冻干或喷雾干燥的）的制剂，其包含至少一种成膜表面活性剂和可用于诊断成像的气体或气体混合物，其制备方法和可通过重构获得的悬浮液 所述制剂具有用于对比成像的水性载体。 本发明还涉及包含与气体接触的干燥材料的容器。 与干燥材料相关联的气体处于低于大气压的压力。
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68.发明授权
公开(公告)号：US5980937A
公开(公告)日：1999-11-09
申请号：US909827
申请日：1997-08-12
CPC分类号： A61K9/1277 , Y10S514/945 , Y10T428/2984
摘要： The invention relates to a dry deposit as a precursor to liposome vesicles, the precursor being a three dimensional expanded structure with bulk density between 0.01 and 0.001 g/cm.sup.3. The invention also concerns a method of making liposome vesicles with an enhanced entrapment capacity by dissolving one or more film forming lipids in at least one organic solvent to form a solution in a reaction vessel, evaporating the solvent to form an expanded three dimensional porous lipid structure, contacting the lipid deposit with an aqueous carrier phase, and producing liposome vesicles entrapping the carrier phase as well as an apparatus comprising an array of tubing or an inert packing which serves as a material support or a matrix surface for the deposition of lipids produced according to the method.
摘要翻译： 本发明涉及作为脂质体囊泡前体的干沉积物，该前体是体积密度在0.01至0.001g / cm 3之间的三维膨胀结构。 本发明还涉及通过将一种或多种成膜脂质溶解在至少一种有机溶剂中以形成溶液在反应容器中，使溶剂蒸发以形成扩展的三维多孔脂质结构，从而制备具有增强的捕获能力的脂质体囊泡的方法 使脂质沉积物与水性载体相接触，并产生包裹载体相的脂质体囊泡，以及包含管阵列或惰性填料的装置，其用作材料载体或基质表面，用于沉积根据 的方法。
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公开(公告)号：US5895661A
公开(公告)日：1999-04-20
申请号：US909097
申请日：1997-08-12
CPC分类号： A61K9/1277 , Y10S514/945 , Y10T428/2984
摘要： The invention relates to a dry deposit as a precursor to liposome vesicles, the precursor being a three dimensional expanded structure with bulk density between 0.01 and 0.001 g/cm.sup.3. The invention also concerns a method of making liposome vesicles with an enhanced entrapment capacity by dissolving one or more film forming lipids in at least one organic solvent to form a solution in a reaction vessel, evaporating the solvent to form an expanded three dimensional porous lipid structure, contacting the lipid deposit with an aqueous carrier phase, and producing liposome vesicles entrapping the carrier phase as well as an apparatus comprising an array of tubing or an inert packing which serves as a material support or a matrix surface for the deposition of lipids produced according to the method.
摘要翻译： 本发明涉及作为脂质体囊泡前体的干沉积物，该前体是体积密度在0.01至0.001g / cm 3之间的三维膨胀结构。 本发明还涉及通过将一种或多种成膜脂质溶解在至少一种有机溶剂中以形成溶液在反应容器中，使溶剂蒸发以形成扩展的三维多孔脂质结构，从而制备具有增强的捕获能力的脂质体囊泡的方法 使脂质沉积物与水性载体相接触，并产生包裹载体相的脂质体囊泡，以及包含管阵列或惰性填料的装置，其用作材料载体或基质表面，用于沉积根据 的方法。
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公开(公告)号：US5446138A
公开(公告)日：1995-08-29
申请号：US939501
申请日：1992-09-08
IPC分类号： C12N15/09 , A01N63/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N9/24 , C12N15/29 , C12N15/56 , C12N15/70 , C12N15/80 , C12N15/81 , C12N15/82 , C12R1/19 , C12R1/865 , C07H21/04 , C12N5/14
CPC分类号： A01N63/00 , C12N15/70 , C12N15/80 , C12N15/81 , C12N15/8257 , C12N9/2442 , C12Y302/01014 , C07K2319/02
摘要： Recombinant DNA which codes for a protein with endochitinase activity or for a precursor thereof, comprising the sequence (a1) (SEQ ID NO. 1).
摘要翻译： 编码具有内切素酶活性的蛋白质或其前体的重组DNA，其包含序列（a1）（SEQ ID NO.1）。
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