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1. 发明申请

WO2013032709A3 SYSTEMS AND METHODS FOR SHELL ENCAPSULATION 审中-公开
公开(公告)号：WO2013032709A3
公开(公告)日：2013-03-07
申请号：PCT/US2012/050916
申请日：2012-08-15
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , WEITZ, David, A. , SHUM, Ho, Cheung , ZHAO, Yuanjin , SUN, Bingjie , HOLTZE, Christian
发明人： WEITZ, David, A. , SHUM, Ho, Cheung , ZHAO, Yuanjin , SUN, Bingjie , HOLTZE, Christian
IPC分类号： B01J13/20 , A01N25/28 , A23P1/04 , A61K9/50 , C09B67/00 , C11D3/50 , C11D17/00
摘要： 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.

2. 发明申请

WO2011146858A2 FOAMS, INCLUDING MICROCELLULAR FOAMS, CONTAINING COLLOIDAL PARTICULATES 审中-公开
标题翻译： FOAMS，包括微胶囊，含有胶体颗粒
公开(公告)号：WO2011146858A2
公开(公告)日：2011-11-24
申请号：PCT/US2011/037377
申请日：2011-05-20
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , LADAVAC, Kosta , GUERRA, Rodrigo, E. , KAZ, David , MANOHARAN, Vinothan , RIEGER, Jens, B. , KOLTZENBURG, Roland, Sebastian , WEITZ, David, A.
发明人： LADAVAC, Kosta , GUERRA, Rodrigo, E. , KAZ, David , MANOHARAN, Vinothan , RIEGER, Jens, B. , KOLTZENBURG, Roland, Sebastian , WEITZ, David, A.
IPC分类号： A61K9/12 , A61K9/14 , A61K9/51
CPC分类号： A61K9/122 , A61K9/143 , A61K9/146 , A61K9/5115
摘要： The present invention generally relates to foams and particles made from such foams, for applications such as drug delivery. The foams or particles may comprise a pharmaceutically acceptable polymeric carrier. In some cases, the foams may include colloidal particulates. A first aspect of the present invention is generally related to polymer-based foams or particles containing pharmaceutically active agents. In some cases, the foam or particle may contain smaller colloidal particulates therein. Such colloidal particulates may be used, for example, to limit the amount of material within certain regions of the foam, or exclude pharmaceutically active agents from being located within certain portions of the foam, which may useful for enhancing release of pharmaceutically active agents from the foam. In some cases, the colloidal particulates may cause the foam or particle to have an unexpectedly high specific surface area. The foam, in certain embodiments, can exhibit a relatively high loading of the pharmaceutically active agent. The foam may be microcellular in certain instances. The foam may also be created using a supercritical fluid, for example, supercritical C0 2 . For instance, a precursor to the foam, containing a pharmaceutically active agent, a pharmaceutically acceptable polymeric carrier, and colloidal particulates, can be mixed with a foaming agent. The pressure may then be decreased, thereby causing the foaming agent to expand and causing a foam to form. The foam may also be ground or milled, or otherwise processed, to form particles such as nanoparticles.
摘要翻译：本发明一般涉及由这种泡沫制成的泡沫和颗粒，用于诸如药物递送的应用。泡沫或颗粒可以包含药学上可接受的聚合物载体。在一些情况下，泡沫可以包括胶体颗粒。本发明的第一方面通常涉及基于聚合物的泡沫或含有药物活性剂的颗粒。在一些情况下，泡沫或颗粒中可含有较小的胶体颗粒。这种胶体颗粒可以用于例如限制泡沫的某些区域内的物质的量，或者不排除药物活性剂位于泡沫的某些部分内，其可用于增强药物活性剂从泡沫。在一些情况下，胶体颗粒可能导致泡沫或颗粒具有出乎意料的高比表面积。在某些实施方案中，泡沫体可以表现出相对高的药物活性剂的负载量。泡沫在某些情况下可能是微孔的。泡沫也可以使用超临界流体，例如超临界CO 2来产生。例如，含有药物活性剂，药学上可接受的聚合物载体和胶体颗粒的泡沫的前体可与发泡剂混合。然后可以降低压力，从而使发泡剂膨胀并形成泡沫。泡沫也可以研磨或研磨或以其它方式处理，以形成颗粒如纳米颗粒。

3. 发明申请

WO2010104593A3 SYSTEMS AND METHODS OF TEMPLATING USING PARTICLES SUCH AS COLLOIDAL PARTICLES 审中-公开
公开(公告)号：WO2010104593A3
公开(公告)日：2010-09-16
申请号：PCT/US2010/000748
申请日：2010-03-12
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , WEITZ, David, A. , KOLTZENBURG, Roland, S. , RIEGER, Jens, B. , STUDART, Andre, R. , WILKING, James, N.
发明人： WEITZ, David, A. , KOLTZENBURG, Roland, S. , RIEGER, Jens, B. , STUDART, Andre, R. , WILKING, James, N.
IPC分类号： B01J2/22 , B01J2/08
摘要： The present invention generally relates to systems and methods for using particle templating, e.g., to produce composites, discrete particles, or the like. In some embodiments, the present invention generally relates to the production of particles using the interstitial spaces between templating elements in a template structure. For example, a plurality of templating elements, which can include colloidal particles, may be arranged to form a template structure. The interstices of the templating elements can provide regions in which a fluid may be introduced. The fluid may be hardened (e.g., solidified) in some cases, e.g., to form a composite comprising the templating elements and the interstitial segments. In certain embodiments, the template structure may then be broken down to release the hardened fluid, e.g., as a plurality of discrete particles.

4. 发明申请

WO2014047236A9 SYSTEMS AND METHODS FOR SPRAY DRYING IN MICROFLUIDIC AND OTHER SYSTEMS 审中-公开
公开(公告)号：WO2014047236A9
公开(公告)日：2014-03-27
申请号：PCT/US2013/060522
申请日：2013-09-19
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE
发明人： AMSTAD, Esther , HOLTZE, Christian , WEITZ, David, A.
IPC分类号： B01J2/02
摘要： 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.

5. 发明申请

WO2013163246A2 POLYMERIZATION REACTIONS WITHIN MICROFLUIDIC DEVICES 审中-公开
标题翻译：微流体装置中的聚合反应
公开(公告)号：WO2013163246A2
公开(公告)日：2013-10-31
申请号：PCT/US2013/037895
申请日：2013-04-24
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE
发明人： ZIERINGER, Maximilian , HOLTZE, Christian , WEITZ, David, A. , SIEBERT, Joerg Max, Georg, Erich
IPC分类号： C08F293/00
CPC分类号： C08F2/22 , B01F3/0807 , B01F13/0062 , B01F13/0093 , B01F2005/0031 , B01J19/0093 , B01J2219/00792 , B01J2219/00833 , B01J2219/0084 , B01J2219/00891 , B01J2219/00903 , B01J2219/00936 , B01J2219/00961 , B01J2219/00963 , B01J2219/00966 , B01J2219/0097 , C08F2/01 , C08F293/005
摘要： 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.
摘要翻译：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

WO2012087350A3 SPRAY DRYING TECHNIQUES 审中-公开
公开(公告)号：WO2012087350A3
公开(公告)日：2012-06-28
申请号：PCT/US2011/001993
申请日：2011-12-20
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , ABATE, Adam, R. , THIELE, Julian, W.P. , WEITZ, David, A. , WINDBERGS, Maike , HOLTZE, Christian
发明人： ABATE, Adam, R. , THIELE, Julian, W.P. , WEITZ, David, A. , WINDBERGS, Maike , HOLTZE, Christian
IPC分类号： B01J2/04 , B05B7/04
摘要： 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.

7. 发明申请

WO2011146852A2 FOAM OR PARTICLES FOR APPLICATIONS SUCH AS DRUG DELIVERY 审中-公开
标题翻译：用于药物递送应用的泡沫或颗粒
公开(公告)号：WO2011146852A2
公开(公告)日：2011-11-24
申请号：PCT/US2011/037363
申请日：2011-05-20
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , LADAVAC, Kosta , GUERRA, Rodrigo, E. , KAZ, David , MANOHARAN, Vinotham , RIEGER, Jens, B. , KOLTZENBURG, Roland, Sebastian , WEITZ, David, A.
发明人： LADAVAC, Kosta , GUERRA, Rodrigo, E. , KAZ, David , MANOHARAN, Vinotham , RIEGER, Jens, B. , KOLTZENBURG, Roland, Sebastian , WEITZ, David, A.
IPC分类号： A61K9/12 , A61K47/32 , A61K9/00
CPC分类号： A61K9/122 , A61K9/146 , A61K47/32
摘要： The present invention generally relates to foams and, in particular, to foams for applications such as drug delivery, and particles that are made from such foams. One aspect relates to foams or particles containing pharmaceutically active agents. The foam may comprise a pharmaceutically acceptable polymeric carrier. In some cases, the foam or particle has an unexpectedly high specific surface area. A high specific surface area may, in some cases, facilitate delivery or release of the pharmaceutically active agent when the foam or particles made from the foam (e.g., by milling) are administered to a subject. The foam may also exhibit a relatively high loading of the pharmaceutically active agent. In some cases, the foam may be a microcellular foam. In one set of embodiments, the foam is created using a supercritical fluid, such as supercritical C02. For example, a precursor to the foam, containing a pharmaceutically active agent, may be mixed with a foaming agent, then the pressure decreased to cause the foaming agent to expand, thereby causing a foam to form. The foam may then be subsequently ground or milled, or otherwise processed to form particles.
摘要翻译：本发明一般涉及泡沫，特别是泡沫用于例如药物递送的泡沫，以及由这种泡沫制成的颗粒。一个方面涉及含有药物活性剂的泡沫或颗粒。泡沫可以包含药学上可接受的聚合物载体。在一些情况下，泡沫或颗粒具有出乎意料的高比表面积。在一些情况下，当由泡沫制成的泡沫或颗粒（例如通过研磨））施用于受试者时，高比表面积可能有助于药物活性剂的递送或释放。泡沫体也可表现出相当高的药物活性剂负荷。在一些情况下，泡沫可以是微孔泡沫。在一组实施方案中，使用超临界流体（例如超临界CO 2）产生泡沫。例如，含有药物活性剂的泡沫体的前体可与发泡剂混合，然后降低压力，引起发泡剂膨胀，从而形成泡沫。然后可以将泡沫研磨或研磨，或以其它方式加工形成颗粒。

8. 发明申请

WO2012027378A3 PARTICLES FOR DRUG DELIVERY AND OTHER APPLICATIONS 审中-公开
公开(公告)号：WO2012027378A3
公开(公告)日：2012-03-01
申请号：PCT/US2011/048822
申请日：2011-08-23
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , FAN, Ben , KOLTZENBURG, Roland, S. , RIEGER, Jens, B. , WEITZ, David, A.
发明人： FAN, Ben , KOLTZENBURG, Roland, S. , RIEGER, Jens, B. , WEITZ, David, A.
IPC分类号： A61K9/14 , A61K9/16 , A61K31/565 , A61K31/58
摘要： The present invention generally relates to particles for drug delivery and other applications. In one aspect, the present invention relates to a technique for reacting precursor compounds in the presence of a pharmaceutically- active agent to form product (e.g., in the form of particles) in which the agent is substantially contained within the product, and the product is soluble within typical gastric fluid of a mammal. In another aspect, the present invention is generally directed to particles comprising an inorganic pharmaceutically acceptable carrier, such as CaCO 3 , and an agent. In some cases, at least some of the agent contained within the particles is fluidically inaccessible from externally of the particle. For instance, the agent may be present in isolated domains within the particle. In another aspect, the present invention is generally directed to methods of creating particles. For instance, according to one set of embodiments, two fluids containing reactants are mixed where, upon reaction of the reactants, an insoluble product is formed, which precipitates to form particles. In one example, a first fluid containing dissolved carbonate ions and a second fluid containing dissolved calcium ions and a pharmaceutically- active agent are mixed together; upon mixing of the first and second fluids, the calcium ions and the carbonate ions form calcium carbonate, which precipitates to form a co-precipitate with the pharmaceutically- active agent. Yet other aspects of the present invention are directed to particles formed from such reactions, methods of using such reactions, methods of promoting such reactions, kits involving particles, or the like.

9. 发明申请

WO2011116154A2 MELT EMULSIFICATION 审中-公开
公开(公告)号：WO2011116154A2
公开(公告)日：2011-09-22
申请号：PCT/US2011/028754
申请日：2011-03-17
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , SHUM, Ho, Cheung , SUN, Bingjie , WEITZ, David, A. , HOLTZE, Christian
发明人： SHUM, Ho, Cheung , SUN, Bingjie , WEITZ, David, A. , HOLTZE, Christian
IPC分类号： B01J13/00 , B01J13/04 , A01N25/28 , A61K9/50 , C09B67/00 , C11D3/50 , C11D17/00
CPC分类号： B01J13/0086 , B01F3/0807 , B01F13/0062 , B01F2005/0034 , B01J13/04 , C09B67/0009 , C09B67/0097 , G01N2015/1413
摘要： 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.
摘要翻译：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。

10. 发明申请

WO2011028760A2 MULTIPLE EMULSIONS CREATED USING JUNCTIONS 审中-公开
标题翻译：使用结果创建的多个乳液
公开(公告)号：WO2011028760A2
公开(公告)日：2011-03-10
申请号：PCT/US2010/047458
申请日：2010-09-01
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , WEITZ, David, A. , ROMANOWSKY, Mark , HOLTZE, Christian
发明人： WEITZ, David, A. , ROMANOWSKY, Mark , HOLTZE, Christian
IPC分类号： B01F5/00 , B01F3/08 , B01F15/04
CPC分类号： B01F13/0084 , B01F3/0807 , B01F2003/0838 , Y10T137/0318 , Y10T137/87571
摘要： 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.
摘要翻译：本发明一般涉及乳液，并且更具体地涉及多重乳液。在一个方面，使用多个通道（诸如微流体通道）在相同的交叉点处相遇来形成多个乳液。在一些实施例中，可以在单个通用交叉点处创建多重乳液，这与需要多通道交叉点以产生多重乳液的其他现有技术系统不同。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处相交，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。取决于应用，第三通道（如果存在）可以是相对亲水的或疏水的。出口通道可以是疏水的，亲水的，或者可以包含至少一个相对亲水的部分和至少一个相对亲水的部分。通过控制通过通道的亲水部分和疏水部分的流体流动，由于流体进入共同交叉点之间的相互作用，可以在公共交叉点附近形成多个乳液。在其他实施例中，可以使用不同图案的亲水或疏水通道。本发明的其他方面通常涉及制造和使用这样的系统的方法，涉及这种系统的试剂盒，使用这种系统创建的乳剂等。

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