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    • 1. 发明专利
    • emulsificação por fusão
    • BR112012023441A2
    • 2016-05-24
    • BR112012023441
    • 2011-03-17
    • BASF SEPRESIDENT AND FELLOWS OF HAVARD COLLEGE
    • SUN BINGJIEHOLTZE CHRISTIANWEITZ DAVID ASHUM HO CHEUNG
    • A61K9/50A01N25/28B01J13/00B01J13/04C09B67/00C11D3/50C11D17/00
    • emulsificação por fusão. a presente invenção refere-se de modo geral a sistemas coloidais, que podem incluir partículas coloidais e/ou outros tipos de partículas. um aspecto da invenção está direcionada geralmente a um sistema que compreende gotículas fluídicas que podem ser pelo menos parcialmente solidificadas, por exemplo, para formar partículas coloidais. em algumas modalidades, são formadas partículas que compreendem pelo menos uma fase externa parcialmente sólida que encapsula uma fase interna. a fase interna pode ser qualquer fase, por exemplo, um sólido, um líquido ou um gás. em alguns casos, solidificar pelo menos uma porção da fase externa das gotículas para formar partículas pode aumentar a estabilidade das partículas e/ou do sistema coloidal que contém as partículas. em um grupo de modalidades, fundir ou liquefazer a fase externa das partículas (por exemplo, pelo aquecimento da partícula a uma temperatura acima da temperatura limiar) pode permitir a liberação de um agente contido dentro da fase interna e/ou permitir que a fase interna aglutine com a fase externa das partículas. a temperatura de fusão da fase externa pode ser controlada em algumas modalidades tal que a fase externa fundirá acima de uma temperatura predeterminada. em algumas modalidades, as partículas podem ser formadas para serem essencialmente livre de um agente estabilizador auxiliar. em algumas modalidades, um agente pode ser encapsulado dentro de uma partícula com eficiência relativamente alta. outros aspectos da invenção são direcionados de modo geral para métodos de fazer e usar tais sistemas coloidais, por exemplo, contendo tais partículas, kits que envolvem tais sistemas coloidais ousimilaressimilares.
    • 2. 发明申请
    • MELT EMULSIFICATION
    • WO2011116154A3
    • 2012-06-07
    • PCT/US2011028754
    • 2011-03-17
    • HARVARD COLLEGEBASF SESHUM HO CHEUNGSUN BINGJIEWEITZ DAVID AHOLTZE CHRISTIAN
    • SHUM HO CHEUNGSUN BINGJIEWEITZ DAVID AHOLTZE CHRISTIAN
    • B01J13/00A01N25/28A61K9/50B01J13/04C09B67/00C11D3/50C11D17/00
    • B01J13/0086B01F3/0807B01F13/0062B01F2005/0034B01J13/04C09B67/0009C09B67/0097G01N2015/1413
    • The present invention generally relates to colloidal systems, which may include colloidal particles and/or other types of particles. One aspect of the invention is generally directed to a system comprising fluidic droplets that can be at least partially solidified, e.g., to form colloidal particles. In some embodiments, particles comprising an at least partially solid outer phase encapsulating an inner phase are formed. The inner phase may be any phase, e.g., a solid, a liquid, or a gas. In some cases, solidifying at least a portion of the outer phase of the droplets to form particles may increase the stability of the particles and/or the colloidal system containing the particles. In one set of embodiments, melting or liquefying the outer phase of the particles (for example, by heating the particle to a temperature above a threshold temperature) can allow release of an agent contained within the inner phase, and/or allow the inner phase to coalesce with a phase external to the particles. The melting temperature of the outer phase can be controlled in some embodiments such that the outer phase will melt above a predetermined temperature. In some embodiments, the particles may be formed to be essentially free of an auxiliary stabilizing agent. In some embodiments, an agent may be encapsulated within a particle with relatively high efficiency. Other aspects of the invention are generally directed to methods of making and using such colloidal systems, e.g., containing such particles, kits involving such colloidal systems, or the like.
    • 本发明一般涉及胶体体系,其可以包括胶体颗粒和/或其它类型的颗粒。 本发明的一个方面通常涉及包含流体液滴的系统,其可以至少部分地固化,例如形成胶体颗粒。 在一些实施方案中,形成包含至少部分固体外层的包封内相的颗粒。 内相可以是任何相,例如固体,液体或气体。 在一些情况下,固化液滴的外相的至少一部分以形成颗粒可以增加包含颗粒的颗粒和/或胶体体系的稳定性。 在一组实施方案中,熔化或液化颗粒的外相(例如,通过将颗粒加热到高于阈值温度的温度)可以允许包含在内相内的试剂的释放和/或允许内相 以颗粒外部的相合并。 在一些实施方案中,可以控制外相的熔融温度,使得外相将在预定温度以上熔化。 在一些实施方案中,颗粒可以形成为基本上不含辅助稳定剂。 在一些实施方案中,试剂可以以相对高的效率封装在颗粒内。 本发明的其它方面通常涉及制备和使用这种胶体体系的方法,例如含有这种颗粒,涉及这种胶体系的试剂盒等。
    • 3. 发明申请
    • MULTIPLE EMULSIONS CREATED USING JUNCTIONS
    • 使用连接产生多种乳液
    • WO2011028760A3
    • 2011-07-14
    • PCT/US2010047458
    • 2010-09-01
    • HARVARD COLLEGEBASF SEWEITZ DAVID AROMANOWSKY MARKHOLTZE CHRISTIAN
    • WEITZ DAVID AROMANOWSKY MARKHOLTZE CHRISTIAN
    • B01F5/00B01F3/08B01F15/04
    • B01F13/0084B01F3/0807B01F2003/0838Y10T137/0318Y10T137/87571
    • The present invention generally relates to emulsions, and more particularly, to multiple emulsions. In one aspect, multiple emulsions are formed using a plurality of channels, such as microfluidic channels, that meet at a common intersection. The multiple emulsions may be created at a single common intersection in some embodiments, unlike other prior art systems where multiple channel intersections are required to create multiple emulsions. For instance, in one set of embodiments, three, four, or more microfluidic channels may intersect at a common intersection, with two or three serving as inlets and one serving as the outlet. In some embodiments, a first fluidic channel may be relatively hydrophobic, while a second fluidic channel is relatively hydrophilic. The third channel, if present, may be relatively hydrophilic or hydrophobic, depending on the application. The outlet channel may be hydrophobic, hydrophilic, or may comprise at least one portion that is relatively hydrophilic and at least one portion that is relatively hydrophilic. By controlling the flow of fluids through the hydrophilic and hydrophobic portions of the channels, multiple emulsions may be created proximate the common intersection, due to interactions between the fluids entering the common intersection. In other embodiments, different patterns of hydrophilic or hydrophobic channels may be used. Other aspects of the invention are generally directed to methods of making and using such systems, kits involving such systems, emulsions created using such systems, or the like.
    • 本发明一般涉及乳剂,更具体地说涉及多重乳液。 在一个方面,使用多个通道(例如微流体通道)形成多个乳液,其在共同的交叉处相遇。 在一些实施例中,可以在单个公共交叉点处产生多个乳液,与需要多个通道交叉点以产生多个乳液的其它现有技术系统不同。 例如,在一组实施例中,三个,四个或更多个微流体通道可以在共同的交叉点相交,其中两个或三个用作入口,一个用作出口。 在一些实施例中,第一流体通道可以是相对疏水的,而第二流体通道是相对亲水的。 根据应用,第三通道(如果存在)可以是相对亲水或疏水的。 出口通道可以是疏水的,亲水的,或者可以包括至少一个相对亲水的部分和至少一个相对亲水的部分。 通过控制流体通过通道的亲水和疏水部分的流动,由于进入公共交叉点的流体之间的相互作用,可能在公共交叉点附近产生多个乳液。 在其它实施方案中,可以使用不同的亲水或疏水通道图案。 本发明的其它方面通常涉及制造和使用这种系统的方法,涉及这种系统的试剂盒,使用这种系统产生的乳液等。
    • 4. 发明申请
    • POLYMERIZATION REACTIONS WITHIN MICROFLUIDIC DEVICES
    • 微流体装置中的聚合反应
    • WO2013163246A3
    • 2014-01-03
    • PCT/US2013037895
    • 2013-04-24
    • HARVARD COLLEGEBASF SE
    • ZIERINGER MAXIMILIANHOLTZE CHRISTIANWEITZ DAVID ASIEBERT JOERG MAX GEORG ERICH
    • C08F293/00B01F13/00B01J14/00B01J19/00B82Y40/00C08F2/01C08F2/12
    • C08F2/22B01F3/0807B01F13/0062B01F13/0093B01F2005/0031B01J19/0093B01J2219/00792B01J2219/00833B01J2219/0084B01J2219/00891B01J2219/00903B01J2219/00936B01J2219/00961B01J2219/00963B01J2219/00966B01J2219/0097C08F2/01C08F293/005
    • The present invention generally relates to polymerization reactions within microfluidic devices. In certain cases, the invention allows for precise control of the polymerization of different types of monomers to form a copolymer by controlling the steps of polymerization and/or controlling the addition of monomers at various time scales within a microfluidic droplet and/or a microfluidic environment, often to a degree that is unattainable by other block polymerization techniques. For example, in one aspect, the present invention is directed to systems and methods for producing polymers such as block copolymers, gradient polymers, random copolymers, etc. For instance, in one set of embodiments, a first monomer contained within a channel, such as a microfluidic channel, is allowed to polymerize to form a first block of a block copolymer. Additional blocks may be added, for example, by flowing the first block and other monomers through a second channel (which may be an extension of the first channel), by polymerizing additional blocks of the copolymer in other channels, by creating droplets containing one or more blocks and allowing the blocks to polymerize, or the like. In some embodiments, a droplet, such as a multiple emulsion droplet, may be creating containing two or more monomers, which are allowed to polymerize together. Still other embodiments of the invention are generally directed to methods of creating such devices, methods of using such devices, kits involving such devices, or the like.
    • 本发明一般涉及微流体装置内的聚合反应。 在某些情况下,本发明允许通过控制聚合和/或控制在微流体液滴和/或微流体环境内的各种时间尺度添加单体的步骤来精确控制不同类型的单体的聚合以形成共聚物 ,通常达到其它嵌段聚合技术无法达到的程度。 例如,在一个方面,本发明涉及用于生产聚合物如嵌段共聚物,梯度聚合物,无规共聚物等的体系和方法。例如,在一组实施方案中,包含在通道内的第一单体,例如 作为微流体通道,被允许聚合以形成嵌段共聚物的第一嵌段。 可以通过例如通过使第一块和其它单体流过第二通道(其可以是第一通道的延伸),通过在其它通道中聚合共聚物的附加嵌段,通过产生含有一个或多个 更多的块和允许块聚合等。 在一些实施方案中,液滴,例如多重乳液液滴可能产生含有两种或更多种单体,这些单体可一起聚合。 本发明的其它实施例通常涉及创建这种设备的方法,使用这种设备的方法,涉及这种设备的套件等。
    • 6. 发明申请
    • CONTROL OF EMULSIONS, INCLUDING MULTIPLE EMULSIONS
    • 乳液控制,包括多种乳剂
    • WO2012162296A2
    • 2012-11-29
    • PCT/US2012038957
    • 2012-05-22
    • HARVARD COLLEGEBASF SEROTEM ASSAFWEITZ DAVID AABATE ADAM RHOLTZE CHRISTIAN
    • ROTEM ASSAFWEITZ DAVID AABATE ADAM RHOLTZE CHRISTIAN
    • B01F13/00B01F3/08
    • B01F3/0811B01F3/0807B01F13/0062B01F13/0084Y10T137/87571
    • The present invention generally relates to emulsions, and more particularly, to double and other multiple emulsions. Certain aspects of the present invention are generally directed to the creation of double emulsions and other multiple emulsions at a common junction of microfluidic channels. In some cases, the microfluidic channels at the common junction may have substantially the same hydrophobicity. In one set of embodiments, a device may include a common junction of six or more channels, where a first fluid flows through one channel, a second fluid flows through two channels, and a third or carrying fluid flows through two more channels, such that a double emulsion of a first droplet of the first fluid, contained in a second droplet of the second fluid, contained by the carrying fluid, flows away from the common junction through a sixth channel. Other aspects of the invention are generally directed to methods of making and using such systems, kits involving such systems, emulsions created using such systems, or the like.
    • 本发明一般涉及乳液,更具体地说涉及双重和其它多重乳液。 本发明的某些方面通常涉及在微流体通道的共同连接处产生双重乳液和其它多重乳液。 在一些情况下,共同连接处的微流体通道可具有基本上相同的疏水性。 在一组实施例中,装置可以包括六个或更多个通道的公共接头,其中第一流体流过一个通道,第二流体流过两个通道,并且第三或承载流体流过两个以上通道,使得 包含在第二流体的第二液滴中的第一流体的第一液滴的双重乳液由携带流体包含,通过第六通道从公共接头流出。 本发明的其它方面通常涉及制造和使用这种系统的方法,涉及这种系统的试剂盒,使用这种系统产生的乳液等。
    • 7. 发明申请
    • SPRAY DRYING TECHNIQUES
    • 喷雾干燥技术
    • WO2012087350A2
    • 2012-06-28
    • PCT/US2011001993
    • 2011-12-20
    • HARVARD COLLEGEBASF SEABATE ADAM RTHIELE JULIAN W PWEITZ DAVID AWINDBERGS MAIKEHOLTZE CHRISTIAN
    • ABATE ADAM RTHIELE JULIAN W PWEITZ DAVID AWINDBERGS MAIKEHOLTZE CHRISTIAN
    • B01J2/04B05B7/04
    • B01D1/18A61K31/58F26B3/12
    • The present invention generally relates to microfluidics, and to spray drying and other drying techniques. In some aspects, an article containing one or more channels or microfiuidic channels is used to mix one or more fluids prior to spray drying. The mixing may occur immediately before the fluids are expelled through a nozzle or other opening into a drying region of the spray dryer. In one set of embodiments, for example, a first fluid is exposed to a second fluid, then the fluids are exposed to air or other gases before being expelled through a nozzle. In certain instances, the first fluid may contain a dissolved species that may precipitate upon exposure to the second fluid; such precipitation may occur immediately before expulsion through a nozzle or other opening, thereby resulting in controlled precipitation as part of the spray drying process.
    • 本发明一般涉及微流体,以及喷雾干燥和其它干燥技术。 在一些方面,使用含有一种或多种通道或微流体通道的制品在喷雾干燥之前混合一种或多种流体。 在流体通过喷嘴或其它开口排出到喷雾干燥器的干燥区域之前,混合可能发生。 在一组实施例中,例如,第一流体暴露于第二流体,然后在通过喷嘴排出之前将流体暴露于空气或其它气体。 在某些情况下,第一流体可以含有在暴露于第二流体时可能沉淀的溶解物质; 这种沉淀可能在通过喷嘴或其他开口排出之前立即发生,从而导致作为喷雾干燥过程的一部分的受控沉淀。
    • 8. 发明申请
    • SYSTEMS AND METHODS FOR SPRAY DRYING IN MICROFLUIDIC AND OTHER SYSTEMS
    • 微流体和其他系统中喷雾干燥的系统和方法
    • WO2014047236A3
    • 2015-05-28
    • PCT/US2013060522
    • 2013-09-19
    • HARVARD COLLEGEBASF SE
    • AMSTAD ESTHERHOLTZE CHRISTIANWEITZ DAVID A
    • B01J2/02B01F5/04B01F13/00B01J2/04B01L3/02H01J49/04
    • B01D1/20B01J2/02B01J2/04F26B3/12
    • The present invention generally relates to microfluidics, and to spray drying and other drying techniques. By at least partially drying fluids within a microfluidic channel, instead of or in addition to conventional spray drying techniques, better control of the drying process can be achieved in certain aspects of the invention. In addition, various embodiments of the invention are generally directed to systems and methods for drying fluids contained within a channel such as a microfluidic channel. For example, a fluid may be partially or completely dried within a microfluidic channel, prior to being sprayed into a collection region. In some embodiments, gases such as air may be directed into a channel containing a fluid, which may facilitate drying of the fluid. In some cases, the fluid may be accelerated due to the introduction of gases into the channel, and in certain embodiments, droplets of fluid may be disrupted to form smaller droplets as a result. In certain cases, the fluids may also be dried to form supersaturated droplets.
    • 本发明一般涉及微流体,以及喷雾干燥和其它干燥技术。 通过至少部分地干燥微流体通道内的流体,代替常规喷雾干燥技术或除常规喷雾干燥技术之外,可以在本发明的某些方面实现干燥过程的更好控制。 此外,本发明的各种实施方案通常涉及用于干燥包含在通道(例如微流体通道)内的流体的系统和方法。 例如,在喷射到收集区域之前,流体可以在微流体通道内部分或完全干燥。 在一些实施例中,诸如空气的气体可以被引导到包含流体的通道中,这可以促进流体的干燥。 在某些情况下,流体可能由于气体进入通道而被加速,并且在某些实施方案中,结果液体液滴可能被破坏以形成较小的液滴。 在某些情况下,流体也可以被干燥以形成过饱和的液滴。
    • 9. 发明申请
    • SYSTEMS AND METHODS FOR SPRAY DRYING IN MICROFLUIDIC AND OTHER SYSTEMS
    • 用于微流体和其他系统中的喷雾干燥的系统和方法
    • WO2014047236A2
    • 2014-03-27
    • PCT/US2013060522
    • 2013-09-19
    • HARVARD COLLEGEBASF SE
    • AMSTAD ESTHERHOLTZE CHRISTIANWEITZ DAVID A
    • B01J2/02
    • B01D1/20B01J2/02B01J2/04F26B3/12
    • The present invention generally relates to microfluidics, and to spray drying and other drying techniques. By at least partially drying fluids within a microfluidic channel, instead of or in addition to conventional spray drying techniques, better control of the drying process can be achieved in certain aspects of the invention. In addition, various embodiments of the invention are generally directed to systems and methods for drying fluids contained within a channel such as a microfluidic channel. For example, a fluid may be partially or completely dried within a microfluidic channel, prior to being sprayed into a collection region. In some embodiments, gases such as air may be directed into a channel containing a fluid, which may facilitate drying of the fluid. In some cases, the fluid may be accelerated due to the introduction of gases into the channel, and in certain embodiments, droplets of fluid may be disrupted to form smaller droplets as a result. In certain cases, the fluids may also be dried to form supersaturated droplets.
    • 本发明一般涉及微流体,并涉及喷雾干燥和其他干燥技术。 通过至少部分干燥微流体通道内的流体,代替常规喷雾干燥技术或除常规喷雾干燥技术之外,可以在本发明的某些方面实现对干燥过程的更好控制。 另外,本发明的各种实施例通常涉及用于干燥包含在诸如微流体通道的通道内的流体的系统和方法。 例如,流体可以在被喷射到收集区域之前在微流体通道内部分地或完全地被干燥。 在一些实施例中,诸如空气的气体可以被引导到包含流体的通道中,这可以有利于流体的干燥。 在一些情况下,由于向通道中引入气体,流体可能被加速,并且在某些实施例中,流体的液滴可能被破坏以形成更小的液滴。 在某些情况下,流体也可以被干燥以形成过饱和液滴。
    • 10. 发明申请
    • SYSTEMS AND METHODS FOR SHELL ENCAPSULATION
    • 用于壳体封装的系统和方法
    • WO2013032709A2
    • 2013-03-07
    • PCT/US2012050916
    • 2012-08-15
    • HARVARD COLLEGEBASF SEWEITZ DAVID ASHUM HO CHEUNGZHAO YUANJINSUN BINGJIEHOLTZE CHRISTIAN
    • WEITZ DAVID ASHUM HO CHEUNGZHAO YUANJINSUN BINGJIEHOLTZE CHRISTIAN
    • B01J13/20
    • B01J13/203A01N25/28A23L29/015A23P10/30A61K9/501A61K9/5036A61K9/5089C09B67/0097C11D17/0039A01N59/02A01N59/06A01N59/16
    • The present invention generally relates to particles, including particles for drug delivery and other applications. Certain aspects of the invention are generally directed to particles comprising a shell and an interior at least partially contained by the shell. In some embodiments, the particles may be treated to enhance the containment of the interior, for example to reduce transport of an agent into or out of the interior. Such particles may exhibit increased ability to encapsulate agents and/or increased storage life (e.g., due to reduced leakage). For instance, in certain embodiments, any defects, such as cracks, pores, etc. within the shell may be sealed or otherwise treated to reduce transport therethrough, for example, with a solid. In some embodiments, for instance, a first reactant in the interior of a particle may come into contact with a second reactant outside of the particle to form a solid, or other suitable product. The shell may also be treated, e.g., at a later point in time, to cause release of an agent contained within the interior, in certain aspects. For example, the shell may be heated to cause the release of the agent from the particle, or the shell may be exposed to chemical or enzymatic degradation, or a change in osmolarity, to cause release of an agent. Still other aspects of the present invention are generally directed to methods of making or using such particles, kits or devices including such particles, or the like.
    • 本发明通常涉及包括用于药物递送的颗粒和其它应用的颗粒。 本发明的某些方面通常涉及包含壳体和至少部分地由壳体包含的内部的颗粒。 在一些实施方案中,可以处理颗粒以增强内部的容纳,例如减少试剂进入或流出内部的运输。 这样的颗粒可以表现出增加的包封剂的能力和/或增加的储存寿命(例如,由于泄漏减少)。 例如,在某些实施例中,壳体内的任何缺陷,例如裂缝,孔隙等可被密封或以其他方式处理,以减少例如通过固体的运输。 在一些实施方案中,例如,颗粒内部的第一反应物可能与颗粒外部的第二反应物接触以形成固体或其它合适的产物。 在某些方面,外壳也可以例如在稍后的时间点处理,以引起包含在内部中的试剂的释放。 例如,可以加热外壳以使试剂从颗粒中释放,或者壳可能暴露于化学或酶降解或渗透压的变化,导致试剂的释放。 本发明的其它方面通常涉及制造或使用这种颗粒,包括这种颗粒的试剂盒或装置等的方法。