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1. 发明申请

WO2005055979A2 pH TRIGGERABLE POLYMERIC PARTICLES 审中-公开
标题翻译： pH可触变聚合物颗粒
公开(公告)号：WO2005055979A2
公开(公告)日：2005-06-23
申请号：PCT/US2004040135
申请日：2004-12-02
申请人： MASSACHUSETTS INST TECHNOLOGY , LITTLE STEVEN R , ANDERSON DANIEL G , LYNN DAVID M , LANGER ROBERT S
发明人： LITTLE STEVEN R , ANDERSON DANIEL G , LYNN DAVID M , LANGER ROBERT S
IPC分类号： A61K9/00 , A61K9/127 , A61K9/14 , A61K9/16 , A61K9/50 , A61K9/51 , A61K39/00 , A61K48/00 , A61L27/18 , C12N5/08 , C12N15/87 , C12N15/88
CPC分类号： A61K9/1647 , A61K9/1617 , A61K9/1623 , A61K9/1658 , A61K9/5031 , A61K9/5153 , A61K9/5192
摘要： A drug delivery system comprising pH triggerable particles is described. The pH triggerable particles comprise and agent(s) to be delivered, which is encapsulated in a matrix comprising a pH trigger agent and a polymer. Agents including nucleic acids may be delivered intracellularly using the inventive pH triggerable particles. Upon exposure to an acidic environment such as the endosome or phagosome of a cell, the particles dissolve or disrupt due to protonation or an increase in solubility of the pH triggering agent. Pharmaceutical compositions and methods of preparing and administering these particles are also described. These particles may be particularly useful in genetic vaccination.
摘要翻译：描述了包含pH可触发颗粒的药物递送系统。 pH可触发颗粒包含待运送的试剂，其被包封在包含pH触发剂和聚合物的基质中。包含核酸的试剂可以使用本发明的pH可触发颗粒在细胞内递送。当暴露于诸如细胞的内体或吞噬体的酸性环境中时，由于质子化或pH引发剂的溶解度的增加，颗粒溶解或破坏。还描述了制备和施用这些颗粒的药物组合物和方法。这些颗粒在基因疫苗接种中可能特别有用。

2. 发明申请

WO2007078765A2 HIGH-THROUGHPUT FABRICATION OF MICROPARTICLES 审中-公开
标题翻译：高通量微波炉的制造
公开(公告)号：WO2007078765A2
公开(公告)日：2007-07-12
申请号：PCT/US2006047519
申请日：2006-12-13
申请人： MASSACHUSETTS INST TECHNOLOGY , LITTLE STEVEN R , ANDERSON DANIEL G , LANGER ROBERT S
发明人： LITTLE STEVEN R , ANDERSON DANIEL G , LANGER ROBERT S
IPC分类号： C08G77/42
CPC分类号： A61K9/1647 , A61K9/1694
摘要： The optimatization of microparticle formulations has become increasingly difficult given the numerous parameters (e.g., polymer, polymer blend, agent to be delivered, particle size, pharaceutical excipients) that can be varied in preparing microparticles. The high-throughput fabrication of microparticles based on the double emulsion/solvent evaporation technique is therefore a breakthrough in screening and optimizing microparticle formulations for particular characteristics. This new system allows for the preparation of multiple (e.g., over 20, over 50, over 100, over 500, etc.) microparticle formulations in parallel. The system involves the formation of an emulsion containing aqueous bubbles with the payload in an organic phase containing the polymer or polymer blend being used for the microparticles. This first emulsion is then transferred to a larger aqueous phase, and a second water- in-oil-in water emulsion is formed. The organic solvent is then removed, and the resulting particles are optionally washed and/or freeze dried. The resulting microparticles are similar or better than microparticles prepared using the traditional one formulation at a time approach. The high-throughput fabrication of microparticles is particularly useful in optimizing microparticles formulations for drug delivery.
摘要翻译：鉴于在制备微粒中可以变化的许多参数（例如，聚合物，聚合物共混物，待递送的试剂，粒径，药物赋形剂），微粒制剂的优化变得越来越困难。因此，基于双重乳液/溶剂蒸发技术的微粒的高通量制造是筛选和优化微粒制剂以获得特定特征的突破。该新系统允许并行制备多个（例如，超过20个，超过50个，超过100个，超过500个等等）微粒制剂。该系统包括在含有用于微粒的聚合物或聚合物共混物的有机相中形成含有水泡的含水气泡。然后将该第一乳液转移到较大的水相中，并形成第二水包油包水乳液。然后除去有机溶剂，任选地将所得颗粒洗涤和/或冷冻干燥。所得到的微粒类似于或优于使用传统的一种制剂在一段时间内制备的微粒。微粒的高通量制造特别可用于优化用于药物递送的微粒制剂。

3. 发明申请

WO2011044328A3 METHODS TO PREPARE PATCHY MICROPARTICLES 审中-公开
标题翻译：制备贴剂微粒的方法
公开(公告)号：WO2011044328A3
公开(公告)日：2011-09-29
申请号：PCT/US2010051771
申请日：2010-10-07
申请人： UNIV PITTSBURGH , LITTLE STEVEN R , KAMALASANAN KALADHAR
发明人： LITTLE STEVEN R , KAMALASANAN KALADHAR
IPC分类号： B01J13/02 , B01J13/14
CPC分类号： B01J13/18 , Y10T428/2982 , Y10T428/2991
摘要： A method for making microparticles having an exterior surface that includes preparing a self-assembled arrangement of microparticles; contacting the self- assembled microparticles with a patch-forming agent resulting in a microparticle/patch-forming agent assembly having proximal regions between adjacent microparticles and/or proximal regions between a microparticle and another substrate, wherein the patch-forming agent is present in the proximal region; and condensing the patch- forming agent such that a pattern of a plurality of discrete patches of patch-forming agent are formed on the exterior surfaces of the microparticles at the proximal regions. A synthetic microsphere having an exterior spherical surface, wherein the exterior spherical surface comprises a first material and a plurality of discrete, uniformly-dimensioned, patches of a second bioactive material arranged in an orderly array over more than one hemisphere of the microsphere.
摘要翻译：一种制造具有外表面的微粒的方法，所述方法包括制备微粒的自组装排列; 使自组装微粒与补丁形成剂接触，产生微粒/补丁形成剂组件，其具有邻近微粒之间的近侧区域和/或微粒与另一基底之间的近侧区域，其中所述补丁形成剂存在于近端区域; 以及使所述斑块形成剂冷凝，使得在所述近端区域处的所述微粒的外表面上形成斑块形成剂的多个离散贴片的图案。具有外部球形表面的合成微球体，其中所述外部球形表面包含第一材料和多个离散的，均匀尺寸的第二生物活性材料的贴片，所述第二生物活性材料贴片以有序排列的方式排列在所述微球体的多于一个半球上。

4. 发明申请

WO2011031996A3 ENGINEERED MICROPARTICLES FOR MACROMOLECULE DELIVERY 审中-公开
标题翻译：用于大分子量递送的工程微粒
公开(公告)号：WO2011031996A3
公开(公告)日：2011-10-06
申请号：PCT/US2010048465
申请日：2010-09-10
申请人： UNIV PITTSBURGH , LITTLE STEVEN R , ROTHSTEIN SAM
发明人： LITTLE STEVEN R , ROTHSTEIN SAM
IPC分类号： A61K47/36 , A61K9/20 , A61K9/22 , A61K47/30 , A61K47/48
CPC分类号： A61K47/34 , A61K9/1647 , A61K9/1694 , A61K9/48
摘要： A method for making a modified release composition, comprising: selecting a desired active agent and polymer matrix for formulating into a modified release composition; assessing degradation effect on release of the active agent from the composition including plotting polymer molecular weight (Mwr) at onset of active agent release vs. active agent molecular weight (MwA); predicting performance of multiple potential formulations for the composition based on the degradation assessment and average polymer matrix initial molecular weight (Mwo) to define a library of building blocks; determining the optimal ratio of the building blocks to satisfy a specified release profile; and making a modified release composition based on the optimal ratio determination.
摘要翻译：一种制备改性释放组合物的方法，包括：选择用于配制成改良释放组合物的所需活性剂和聚合物基质; 评估活性剂从组合物中释放的降解作用，包括在活性剂释放开始时相对活性剂分子量（MwA）绘制聚合物分子量（Mwr）; 基于降解评估和平均聚合物基质初始分子量（Mwo）预测组合物的多种潜在制剂的性能以确定构件块的文库; 确定构件块的最佳比例以满足指定的释放曲线; 并且基于最佳比率确定制造改良释放组合物。

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