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1. 发明授权

US08846098B2 Artificial cell constructs for cellular manipulation 有权
标题翻译：用于细胞操作的人造细胞构建体
公开(公告)号：US08846098B2
公开(公告)日：2014-09-30
申请号：US13383122
申请日：2010-07-09
申请人： Steven R. Little
发明人： Steven R. Little
IPC分类号： A61K9/00 , A61K9/14 , A61K45/00 , A61K39/395 , A61K38/00 , A61K38/18 , A61K47/48 , A61K38/20
CPC分类号： A61K9/1635 , A61K9/0019 , A61K9/1682 , A61K38/1841 , A61K38/2013 , A61K47/6921 , B01J13/0065 , B01J2208/00823 , A61K2300/00
摘要： The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.
摘要翻译：本发明考虑到免疫耐受性的诱导，从而提供永久的同种异体移植物接受。该方法避免了终生免疫抑制剂方案的需要，这可能增加感染，自身免疫和癌症的风险。免疫耐受被认为是由具有免疫抑制能力的调节性T淋巴细胞（Treg细胞）介导的。预期包含人造构建体的治疗相关平台包括许多可溶性和表面结合的Treg细胞刺激因子，其可诱导同种异体移植后的耐受性。这种细胞大小的人造构造物具有对调节性T细胞表面部分和包封的可溶性调节性T细胞调节因子特异的表面结合单克隆抗体。

2. 发明申请

US20120172456A1 ENGINEERED MICROPARTICLES FOR MACROMOLECULE DELIVERY 审中-公开
标题翻译：用于大分子递送的工程微量元素
公开(公告)号：US20120172456A1
公开(公告)日：2012-07-05
申请号：US13395245
申请日：2010-09-10
申请人： Steven R. Little , Sam Rothstein
发明人： Steven R. Little , Sam Rothstein
IPC分类号： A61K47/34
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：选择所需的活性剂和聚合物基质以配制成改性释放组合物; 评估从组合物中释放活性剂的降解作用，包括在活性剂释放开始时绘制聚合物分子量（Mwr）与活性剂分子量（MwA）的关系; 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配方的性能来定义构建块的文库; 确定构建块的最佳比例以满足指定的释放轮廓; 并基于最佳比例测定制备改性组合物。

3. 发明授权

US09211519B2 Methods to prepare patchy microparticles 有权
标题翻译：制备斑块状微粒的方法
公开(公告)号：US09211519B2
公开(公告)日：2015-12-15
申请号：US13500890
申请日：2010-10-07
申请人： Steven R. Little , Kaladhar Kamalasanan
发明人： Steven R. Little , Kaladhar Kamalasanan
IPC分类号： B01J13/18
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，包括制备微粒的自组装布置; 使自组装的微粒与补片形成剂接触，导致微粒/补片形成剂组合物在微粒与另一底物之间的相邻微粒和/或近区之间具有近侧区域，其中斑块形成剂存在于近端区域并且使所述贴片形成剂冷凝，使得在所述近端区域的所述微粒的外表面上形成多个分散片形成剂片的图案。一种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括第一生物活性物质的第一材料和第二生物活性材料的多个离散的，均匀尺寸的斑块，所述第二生物活性物质按所述微球的多于一个半球的顺序排列。

4. 发明申请

US20120214001A1 METHODS TO PREPARE PATCHY MICROPARTICLES 有权
标题翻译：预处理微生物的方法
公开(公告)号：US20120214001A1
公开(公告)日：2012-08-23
申请号：US13500890
申请日：2010-10-07
申请人： Steven R. Little , Kaladhar Kamalasanan
发明人： Steven R. Little , Kaladhar Kamalasanan
IPC分类号： B32B9/00 , B05D5/00 , B32B5/16 , B05D7/00
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，包括制备微粒的自组装布置; 使自组装的微粒与补片形成剂接触，导致微粒/补片形成剂组合物在微粒与另一底物之间的相邻微粒和/或近区之间具有近侧区域，其中斑块形成剂存在于近端区域并且使所述贴片形成剂冷凝，使得在所述近端区域的所述微粒的外表面上形成多个分散片形成剂片的图案。一种具有外部球形表面的合成微球，其中所述外部球形表面包括第一生物活性材料的第一材料和第二生物活性材料的多个离散且均匀尺寸的贴片，所述第二生物活性材料按所述微球的多于一个半球的顺序排列。

5. 发明申请

US20120148676A1 ARTIFICIAL CELL CONSTRUCTS FOR CELLULAR MANIPULATION 有权
标题翻译：用于细胞操作的人工细胞构建体
公开(公告)号：US20120148676A1
公开(公告)日：2012-06-14
申请号：US13383122
申请日：2010-07-09
申请人： Steven R. Little
发明人： Steven R. Little
IPC分类号： A61K39/395 , A61K9/14 , A61K38/20 , A61P35/00 , A61K9/00 , A61P37/02 , A61P31/00 , A61K38/02 , A61K38/18
CPC分类号： A61K9/1635 , A61K9/0019 , A61K9/1682 , A61K38/1841 , A61K38/2013 , A61K47/6921 , B01J13/0065 , B01J2208/00823 , A61K2300/00
摘要： The present invention contemplates induction of immunological tolerance thereby providing permanent allogcaft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.
摘要翻译：本发明考虑到免疫耐受性的诱导，从而提供永久的同义词接受。该方法避免了终生免疫抑制剂方案的需要，这可能增加感染，自身免疫和癌症的风险。免疫耐受被认为是由具有免疫抑制能力的调节性T淋巴细胞（Treg细胞）介导的。预期包含人造构建体的治疗相关平台包括许多可溶性和表面结合的Treg细胞刺激因子，其可诱导同种异体移植后的耐受性。这种细胞大小的人造构造物具有对调节性T细胞表面部分和包封的可溶性调节性T细胞调节因子特异的表面结合单克隆抗体。

6. 发明申请

US20150374633A1 THERMORESPONSIVE HYDROGEL CONTAINING POLYMER MICROPARTICLES FOR NONINVASIVE OCULAR DRUG DELIVERY 审中-公开
标题翻译：含有聚合物微粒的含氢氢化物非挥发性液体药物递送
公开(公告)号：US20150374633A1
公开(公告)日：2015-12-31
申请号：US14772758
申请日：2014-03-04
申请人： Morgan V. FEDORCHAK , Steven R. LITTLE , Joel S. SCHUMAN , Anthony CUGINI
发明人： Morgan Virginia Fedorchak , Steven R. Little , Joel Steven Schuman , Anthony Cugini
IPC分类号： A61K9/50 , A61K47/34 , A61K9/06 , A61K31/498 , A61K9/00
CPC分类号： A61K9/5021 , A61K9/0048 , A61K9/0051 , A61K9/06 , A61K9/10 , A61K9/5031 , A61K31/498 , A61K47/34
摘要： A method for sustained delivery of an agent to an ocular organ in a subject, comprising topically delivering to the ocular surface a liquid thermoresponsive hydrogel comprising agent-loaded polymer microparticles, wherein the agent is sustainably released for a period of at least five days.
摘要翻译：一种用于将受试者持续递送至受试者眼部器官的方法，包括向所述眼表面局部递送含有载有药剂的聚合物微粒的液体热反应性水凝胶，其中所述试剂可持续释放至少5天的时间。

7. 发明授权

US07943179B2 pH triggerable polymeric particles 有权
标题翻译： pH可触发聚合物颗粒
公开(公告)号：US07943179B2
公开(公告)日：2011-05-17
申请号：US11002542
申请日：2004-12-02
申请人： Steven R. Little , David M. Lynn , Daniel G. Anderson , Robert S. Langer
发明人： Steven R. Little , David M. Lynn , Daniel G. Anderson , Robert S. Langer
IPC分类号： A61K9/16
CPC分类号： A61K9/1617 , A61K9/1623 , A61K9/1647 , A61K9/1658
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。

8. 发明申请

US20090136553A1 TRIGGERABLY DISSOLVABLE HOLLOW FIBERS FOR CONTROLLED DELIVERY 审中-公开
标题翻译：用于控制输送的易燃易爆中空纤维
公开(公告)号：US20090136553A1
公开(公告)日：2009-05-28
申请号：US12237835
申请日：2008-09-25
申请人： Jorg C. Gerlach , Jianjun Guan , Steven R. Little , Alan J. Russell , Jillian Tengood , William R. Wagner
发明人： Jorg C. Gerlach , Jianjun Guan , Steven R. Little , Alan J. Russell , Jillian Tengood , William R. Wagner
IPC分类号： A61F2/04 , C07H3/00 , C08G63/44 , A61K38/18 , C12M3/00 , C08L89/00 , C12N5/06
CPC分类号： A61L27/38 , A61L27/50 , A61L27/54 , A61L2300/414 , A61L2300/45 , A61L2300/602 , D01D5/24
摘要： Provided are tubular structures of a biocompatible, triggerably-dissolvable material such as cellulose or a copolymer having an LCST below physiological temperatures. The structures may be embedded within a cell growth scaffold. The tubular structures are useful in growing 3-dimensional tissue structures because nutrients, cytokines or other cell growth and/or differentiation compounds, as well as drugs, such as antibiotics and steroids, can be administered over time, and the tubular structures can be dissolved non-invasively.
摘要翻译：提供了生物相容性，可触发性可溶解的材料的管状结构，例如在生理温度以下具有LCST的纤维素或共聚物。结构可以嵌入细胞生长支架内。管状结构可用于生长三维组织结构，因为营养物质，细胞因子或其它细胞生长和/或分化化合物以及药物如抗生素和类固醇可随时间施用，并且管状结构可溶解非侵略性

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