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1. 发明授权

US08293486B2 Functionalization of silk material by avidin-biotin interaction 有权
标题翻译：丝素材料通过抗生物素蛋白 - 生物素相互作用进行功能化
公开(公告)号：US08293486B2
公开(公告)日：2012-10-23
申请号：US13381687
申请日：2010-07-20
申请人： David L. Kaplan , Xiaoqin Wang , Monica A. Serban
发明人： David L. Kaplan , Xiaoqin Wang , Monica A. Serban
IPC分类号： G01N33/53 , C07K1/00
CPC分类号： C07K14/43586 , A61K47/64 , A61K47/6903 , A61K47/6921
摘要： The present invention provides for compositions and methods of linking silk fibroin to active agents through the specific interaction between avidin and biotin, providing for functionalization of silk-based protein biomaterials. An avidin- or biotin-modified silk is a biomaterial platform for functionalization with a variety of correspondingly linked active agents, such as antibodies and growth factors. A variety of functionalized silk materials, such as silk hydrogel, silk micro/nanoparticles and silk films, can be prepared by the methods of the present invention. The functionalization strategies of the present invention are relatively easy, fast and feasible, and are thus useful in many biomedical applications.
摘要翻译：本发明提供通过抗生物素蛋白和生物素之间的特异性相互作用将丝素蛋白与活性剂连接的组合物和方法，提供了基于丝的蛋白质生物材料的功能化。抗生物素蛋白或生物素修饰的丝是用于与多种相应连接的活性剂如抗体和生长因子进行功能化的生物材料平台。可以通过本发明的方法制备各种功能性丝绸材料，例如丝素水凝胶，丝微/纳米颗粒和丝膜。本发明的功能化策略相对容易，快速和可行，因此在许多生物医学应用中是有用的。

2. 发明申请

US20120129255A1 FUNCTIONALIZATION OF SILK MATERIAL BY AVIDIN-BIOTIN INTERACTION 有权
标题翻译：通过AVIDIN-BIOTIN相互作用对丝素材料的功能化
公开(公告)号：US20120129255A1
公开(公告)日：2012-05-24
申请号：US13381687
申请日：2010-07-20
申请人： David L. Kaplan , Xiaoqin Wang , Monica A. Serban
发明人： David L. Kaplan , Xiaoqin Wang , Monica A. Serban
IPC分类号： C07K19/00 , C12N5/0783
CPC分类号： C07K14/43586 , A61K47/64 , A61K47/6903 , A61K47/6921
摘要： The present invention provides for compositions and methods of linking silk fibroin to active agents through the specific interaction between avidin and biotin, providing for functionalization of silk-based protein biomaterials. An avidin- or biotin-modified silk is a biomaterial platform for functionalization with a variety of correspondingly linked active agents, such as antibodies and growth factors. A variety of functionalized silk materials, such as silk hydrogel, silk micro/nanoparticles and silk films, can be prepared by the methods of the present invention. The functionalization strategies of the present invention are relatively easy, fast and feasible, and are thus useful in many biomedical applications.
摘要翻译：本发明提供通过抗生物素蛋白和生物素之间的特异性相互作用将丝素蛋白与活性剂连接的组合物和方法，提供了基于丝的蛋白质生物材料的功能化。抗生物素蛋白或生物素修饰的丝是用于与多种相应连接的活性剂如抗体和生长因子进行功能化的生物材料平台。可以通过本发明的方法制备各种功能性丝绸材料，例如丝素水凝胶，丝微/纳米颗粒和丝膜。本发明的功能化策略相对容易，快速和可行，因此在许多生物医学应用中是有用的。

3. 发明授权

US08187616B2 Method for silk fibroin gelation using sonication 有权
标题翻译：使用超声处理丝素蛋白凝胶化方法
公开(公告)号：US08187616B2
公开(公告)日：2012-05-29
申请号：US12601845
申请日：2008-05-29
申请人： Xiaoqin Wang , Jon Kluge , Gary G. Leisk , David L. Kaplan
发明人： Xiaoqin Wang , Jon Kluge , Gary G. Leisk , David L. Kaplan
IPC分类号： A61K9/00 , A61K38/17
CPC分类号： A61K47/42 , A61K9/06 , A61K9/5052 , A61K9/5063 , A61K9/5089 , A61K35/28 , A61K2035/124 , C07K14/43586
摘要： This invention provides for a process of rapidly forming silk fibroin gelation through ultrasonication. Under the appropriate conditions, gelation can be controlled to occur within two hours after the ultrasonication treatment. Biological materials, including viable cells, or therapeutic agents can be encapsulated in the hydrogels formed from the process and be used as delivery vehicles.
摘要翻译：本发明提供了通过超声波快速形成丝素蛋白凝胶化的方法。在适当的条件下，超声波处理后两小时即可控制凝胶化。包括活细胞或治疗剂在内的生物材料可以包封在由该方法形成的水凝胶中并用作输送载体。

4. 发明申请

US20100028451A1 SILK MICROSPHERES FOR ENCAPSULATION AND CONTROLLED RELEASE 审中-公开
标题翻译：用于封装和控制释放的SILK微孔
公开(公告)号：US20100028451A1
公开(公告)日：2010-02-04
申请号：US12442595
申请日：2007-09-26
申请人： David L. Kaplan , Xiaoqin Wang
发明人： David L. Kaplan , Xiaoqin Wang
IPC分类号： A61K9/14 , A61K38/02 , A61K31/7088 , A61K39/395 , A61K38/43 , A61K38/16 , A61K38/21 , A61K38/20 , A61K38/28
CPC分类号： A61K38/44 , A61K9/127 , A61K9/16 , A61K9/1658 , A61K9/19 , A61K9/5052 , A61K31/7076 , A61K47/34 , A61K47/42
摘要： A method was developed to prepare silk fibroin microspheres using lipid vesicles as templates to efficiently load therapeutic agents in active form for controlled release. The lipids are subsequently removed through the use of a dehydration agent, such as methanol or sodium chloride, resulting in β-sheet structure dominant silk microsphere structures having about 2 μm in diameter. The therapeutic agent can be entrapped in the silk microspheres and used in pharmaceutical formulations for controlled-release treatments.
摘要翻译：开发了一种使用脂质囊泡作为模板来制备丝素蛋白微球的方法，以有效地加载活性形式的治疗剂用于控制释放。随后通过使用脱水剂如甲醇或氯化钠除去脂质，得到具有约2μm直径的β-片状结构优势的丝微球结构。治疗剂可以包埋在丝微球中并用于药物制剂中用于控制释放处理。

5. 发明授权

US08722067B2 Method for silk fibroin gelation using sonication 有权
标题翻译：使用超声处理丝素蛋白凝胶化方法
公开(公告)号：US08722067B2
公开(公告)日：2014-05-13
申请号：US13457705
申请日：2012-04-27
申请人： Xiaoqin Wang , Jon Kluge , Gary G. Leisk , David L. Kaplan
发明人： Xiaoqin Wang , Jon Kluge , Gary G. Leisk , David L. Kaplan
IPC分类号： A61K9/00 , A61K38/17
CPC分类号： A61K47/42 , A61K9/06 , A61K9/5052 , A61K9/5063 , A61K9/5089 , A61K35/28 , A61K2035/124 , C07K14/43586
摘要： This invention provides for a process of rapidly forming silk fibroin gelation through ultrasonication. Under the appropriate conditions, gelation can be controlled to occur within two hours after the ultrasonication treatment. Biological materials, including viable cells, or therapeutic agents can be encapsulated in the hydrogels formed from the process and be used as delivery vehicles.
摘要翻译：本发明提供了通过超声波快速形成丝素蛋白凝胶化的方法。在适当的条件下，超声波处理后两小时即可控制凝胶化。包括活细胞或治疗剂在内的生物材料可以包封在由该方法形成的水凝胶中并用作输送载体。

6. 发明授权

US08715740B2 Silk nanospheres and microspheres and methods of making same 有权
标题翻译：丝纳米球和微球及其制备方法
公开(公告)号：US08715740B2
公开(公告)日：2014-05-06
申请号：US13496227
申请日：2010-09-29
申请人： Xiaoqin Wang , David L. Kaplan
发明人： Xiaoqin Wang , David L. Kaplan
IPC分类号： A61K9/50 , A61K9/127 , B01J13/02
CPC分类号： A61K9/5169 , A61K9/14 , A61K9/1605 , A61K9/1647 , A61K9/5052 , A61K9/5089 , A61K9/5192 , A61K31/352 , Y10T428/2982
摘要： The present invention provides for methods of preparing silk nanoparticles and microparticles, methods of encapsulating an active agent into the silk nano- and microparticles and compositions comprising these silk particles.
摘要翻译：本发明提供了制备丝纳米颗粒和微粒的方法，将活性剂包封在丝纳米和微粒中的方法和包含这些丝颗粒的组合物。

7. 发明申请

US20100178304A1 METHOD FOR SILK FIBROIN GELATION USING SONICATION 有权
标题翻译：使用声音的丝光纤凝胶的方法
公开(公告)号：US20100178304A1
公开(公告)日：2010-07-15
申请号：US12601845
申请日：2008-05-29
申请人： Xiaoqin Wang , Jon Kluge , Gary G. Leisk , David L. Kaplan
发明人： Xiaoqin Wang , Jon Kluge , Gary G. Leisk , David L. Kaplan
IPC分类号： A61K9/00 , C07K14/435 , A61K45/00 , A61K35/12 , A61K38/16 , A61K38/00 , A61K39/395 , A61K38/43 , A61K31/7088 , A61P43/00
CPC分类号： A61K47/42 , A61K9/06 , A61K9/5052 , A61K9/5063 , A61K9/5089 , A61K35/28 , A61K2035/124 , C07K14/43586
摘要： This invention provides for a process of rapidly forming silk fibroin gelation through ultrasonication. Under the appropriate conditions, gelation can be controlled to occur within two hours after the ultrasonication treatment. Biological materials, including viable cells, or therapeutic agents can be encapsulated in the hydrogels formed from the process and be used as delivery vehicles.
摘要翻译：本发明提供了通过超声波快速形成丝素蛋白凝胶化的方法。在适当的条件下，超声波处理后两小时即可控制凝胶化。包括活细胞或治疗剂在内的生物材料可以包封在由该方法形成的水凝胶中并用作输送载体。

8. 发明申请

US20130171260A1 SILK MICROSPHERES FOR ENCAPSULATION AND CONTROLLED RELEASE 审中-公开
标题翻译：用于封装和控制释放的SILK微孔
公开(公告)号：US20130171260A1
公开(公告)日：2013-07-04
申请号：US13778402
申请日：2013-02-27
申请人： David L. Kaplan , Xiaoqin Wang
发明人： David L. Kaplan , Xiaoqin Wang
IPC分类号： A61K9/50
CPC分类号： A61K38/44 , A61K9/127 , A61K9/16 , A61K9/1658 , A61K9/19 , A61K9/5052 , A61K31/7076 , A61K47/34 , A61K47/42
摘要： A method was developed to prepare silk fibroin microspheres using lipid vesicles as templates to efficiently load therapeutic agents in active form for controlled release. The lipids are subsequently removed through the use of a dehydration agent, such as methanol or sodium chloride, resulting in β-sheet structure dominant silk microsphere structures having about 2 μm in diameter. The therapeutic agent can be entrapped in the silk microspheres and used in pharmaceutical formulations for controlled-release treatments.
摘要翻译：开发了一种使用脂质囊泡作为模板来制备丝素蛋白微球的方法，以有效地加载活性形式的治疗剂用于控制释放。随后通过使用脱水剂如甲醇或氯化钠除去脂质，得到具有约2μm直径的β-片状结构优势的丝微球结构。治疗剂可以包埋在丝微球中并用于药物制剂中用于控制释放处理。

9. 发明申请

US20130060008A1 METHOD FOR SILK FIBROIN GELATION USING SONICATION 有权
公开(公告)号：US20130060008A1
公开(公告)日：2013-03-07
申请号：US13457705
申请日：2012-04-27
申请人： Xiaoqin Wang , Jon Kluge , Gary G. Leisk , David L. Kaplan
发明人： Xiaoqin Wang , Jon Kluge , Gary G. Leisk , David L. Kaplan
IPC分类号： C07K14/435
CPC分类号： A61K47/42 , A61K9/06 , A61K9/5052 , A61K9/5063 , A61K9/5089 , A61K35/28 , A61K2035/124 , C07K14/43586
摘要： This invention provides for a process of rapidly forming silk fibroin gelation through ultrasonication. Under the appropriate conditions, gelation can be controlled to occur within two hours after the ultrasonication treatment. Biological materials, including viable cells, or therapeutic agents can be encapsulated in the hydrogels formed from the process and be used as delivery vehicles.

10. 发明申请

US20120187591A1 SILK NANOSPHERES AND MICROSPHERES AND METHODS OF MAKING SAME 有权
标题翻译：丝素纳米微粒和微球及其制备方法
公开(公告)号：US20120187591A1
公开(公告)日：2012-07-26
申请号：US13496227
申请日：2010-09-29
申请人： Xiaoqin Wang , David L. Kaplan
发明人： Xiaoqin Wang , David L. Kaplan
IPC分类号： B29B9/16 , B29B9/00 , A61K9/50 , C07K14/00 , B82Y5/00 , B82Y30/00
CPC分类号： A61K9/5169 , A61K9/14 , A61K9/1605 , A61K9/1647 , A61K9/5052 , A61K9/5089 , A61K9/5192 , A61K31/352 , Y10T428/2982
摘要： The present invention provides for methods of preparing silk nanoparticles and microparticles, methods of encapsulating an active agent into the silk nano- and microparticles and compositions comprising these silk particles. In particular, the silk spheres are prepared from phase separation of silk and polyvinyl alcohol (PVA), without exposure to an organic solvent. The method employs a chemical, PVA, which is an FDA-approved ingredient in drug formulations. Different parameters can be adjusted to control the size and shape of the silk spheres during the fabrication process. The silk particle compositions of the present invention may also encapsulate active agents or chemicals. Such compositions allow the active agents to be controllably and sustainably released to the target organs or tissues. The silk composition entrapping active agents also provides for a long-term storage medium for the active agents so entrapped. The silk nano- and microparticles of the present invention are thus suitable for a variety of biomedical and pharmaceutical applications, such as drug delivery or tissue engineering.
摘要翻译：本发明提供了制备丝纳米颗粒和微粒的方法，将活性剂包封在丝纳米和微粒中的方法和包含这些丝颗粒的组合物。特别地，丝球是通过丝和聚乙烯醇（PVA）的相分离制备的，而不暴露于有机溶剂。该方法采用化学品PVA，它是FDA批准的药物制剂成分。可以调整不同的参数，以在制造过程中控制丝球的尺寸和形状。本发明的丝粒组合物也可以包封活性剂或化学物质。这样的组合物允许活性剂可控地和可持续地释放到靶器官或组织。包埋活性剂的丝绸组合物还为被捕获的活性剂提供长期的储存介质。因此，本发明的丝素纳米颗粒和微粒子适用于各种生物医学和药物应用，例如药物递送或组织工程。

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