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    Delivery of biologically active substance to target sites in the body of patients
    1.
    发明授权
    Delivery of biologically active substance to target sites in the body of patients 有权
    将生物活性物质交付给患者体内的靶点

    公开(公告)号：US06258378B1

    公开(公告)日：2001-07-10

    申请号：US09243787

    申请日：1999-02-03

    申请人： Michel Schneider ,  Feng Yan ,  Agnés Hiver

    发明人： Michel Schneider ,  Feng Yan ,  Agnés Hiver

    IPC分类号： A61K9127

    CPC分类号： A61K9/127 ,  A61K9/0009 ,  A61K41/0028 ,  Y10S424/812 ,  Y10S436/829

    摘要： The invention concerns a method for administering bioactive substances to patients at selected sites in the body and remotely promoting delivery of said media to selected organs or tissues in the body. The method comprises providing an administrable formulation comprising, dispersed in an aqueous carrier liquid, liposomes filled with bioactive substances and gas-filled microspheres, injecting said formulation into the circulation of a patient so that it is directed to a site of interest, and applying ultrasound pulses to said site so as to make the gas-filled microbodies explode and the gas confined therein to expand in the carrier liquid, the energy of expansion of said confined gas causing the liposome vesicles to open and release the trapped substances at said site. Also disclosed are formulations for delivery of biologically active substances to selected target sites in the organism, the formulations comprising an aqueous suspension of gas-filled microvesicles and liposomes filled with active susbstances such as drugs or diagnostic agents. The formulations are available in a kit form in which the kit comprises sterile precursor components.

    摘要翻译： 本发明涉及一种用于向身体中选定部位的患者施用生物活性物质的方法，并远程促进将所述培养基递送至身体中选定的器官或组织。 该方法包括提供可施用的制剂，其包含在水性载体液体中分散有填充有生物活性物质和充气微球的脂质体，将所述制剂注射到患者的循环中，使其被引导到感兴趣的部位，并施加超声波 脉冲到所述位置，以使气体充填的微体体积膨胀，并且其中限制的气体在载体液体中膨胀，所述密闭气体的膨胀能使脂质体囊泡打开并释放所述位点处的被捕获的物质。 还公开了用于将生物活性物质递送到生物体中的选定靶位点的制剂，该制剂包含充满气体的微泡的水性悬浮液和填充有活性物质如药物或诊断剂的脂质体。 制剂可以试剂盒形式获得，其中试剂盒包含无菌前体组分。

    Gas-filled microvesicle assembly for contrast imaging
    3.
    发明申请
    Gas-filled microvesicle assembly for contrast imaging 有权
    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。

    Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method
    5.
    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：US06183725B2

    公开(公告)日：2001-02-06

    申请号：US09021367

    申请日：1998-02-10

    申请人： Feng Yan ,  Michel Schneider

    发明人： Feng Yan ,  Michel Schneider

    IPC分类号： A61B813

    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。

    Stable microbubble suspensions comprising saturated phospholipios for ultrasonic echography
    8.
    发明授权
    Stable microbubble suspensions comprising saturated phospholipios for ultrasonic echography 失效
    稳定的微泡悬浮液，包括用于超声波回波造影的饱和磷脂

    公开(公告)号：US5908610A

    公开(公告)日：1999-06-01

    申请号：US883592

    申请日：1997-06-26

    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 stabiliser 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。

    Gas-filled microvesicle assembly for contrast imaging
    9.
    发明授权
    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.