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1. 发明申请

WO2010042798A2 MODIFIED SILK FILMS CONTAINING GLYCEROL 审中-公开
标题翻译：包含甘油的改性丝绸膜
公开(公告)号：WO2010042798A2
公开(公告)日：2010-04-15
申请号：PCT/US2009/060135
申请日：2009-10-09
申请人： TRUSTEES OF TUFTS COLLEGE , LU, Shenzhou , WANG, Xiaoqin , OMENETTO, Fiorenzo , KAPLAN, David L.
发明人： LU, Shenzhou , WANG, Xiaoqin , OMENETTO, Fiorenzo , KAPLAN, David L.
IPC分类号： A61L27/36 , A61L27/54 , A61F2/02
CPC分类号： A61L27/3604 , A61L27/3804 , A61L27/50 , A61L27/54 , A61L2420/06 , B05D1/30 , B05D3/0254 , B05D3/107 , C08J3/18 , C08J5/18 , C08J2389/00 , C08K5/053 , C12N11/02 , C08L89/00
摘要： The present invention provides for compositions and methods for preparing aqueous insoluble, ductile, flexible silk fibroin films. The silk films comprise silk fibroin and about 10% to about 50% (w/w) glycerol, and are prepared by entirely aqueous processes. The ductile silk film may be further treated by extracting the glycerol from and re-drying the silk film. Active agents may be embedded in or deposited on the glycerol modified silk film for a variety of medical applications. The films may be shaped into 3-dimentional structures, or placed on support surfaces as labels or coatings. The glycerol modified silk films of the present invention are useful in variety of applications such as tissue engineering, medical devices or implants, drug delivery, and edible pharmaceutical or food labels.
摘要翻译：本发明提供了用于制备水不溶性，可延展的柔性丝心蛋白膜的组合物和方法。丝膜包含丝素蛋白和约10％至约50％（w / w）的甘油，并且通过完全含水方法制备。可以通过从丝膜中提取甘油并再次干燥来进一步处理可延展丝膜。活性剂可嵌入或沉积在甘油改性的丝膜上用于各种医学应用。薄膜可以成型为三维结构，或者作为标签或涂层放置在支撑表面上。本发明的甘油改性的丝膜可用于多种应用，例如组织工程，医疗装置或植入物，药物递送和可食用的药物或食品标签。

2. 发明申请

WO2008150861A1 METHOD FOR SILK FIBROIN GELATION USING SONICATION 审中-公开
标题翻译：使用声音的丝光纤凝胶的方法
公开(公告)号：WO2008150861A1
公开(公告)日：2008-12-11
申请号：PCT/US2008/065076
申请日：2008-05-29
申请人： TRUSTEES OF TUFTS COLLEGE , WANG, Xiaoqin , KLUGE, Jon , LEISK, Gary, G. , KAPLAN, David, L.
发明人： WANG, Xiaoqin , KLUGE, Jon , LEISK, Gary, G. , KAPLAN, David, L.
IPC分类号： A61K35/24
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。

3. 发明申请

WO2008118133A2 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：WO2008118133A2
公开(公告)日：2008-10-02
申请号：PCT/US2007/020789
申请日：2007-09-26
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David, L. , WANG, Xiaoqin
发明人： KAPLAN, David, L. , WANG, Xiaoqin
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。

4. 发明申请

WO2011041395A2 SILK NANOSPHERES AND MICROSPHERES AND METHODS OF MAKING SAME 审中-公开
标题翻译：丝素纳米微粒和微球及其制备方法
公开(公告)号：WO2011041395A2
公开(公告)日：2011-04-07
申请号：PCT/US2010/050698
申请日：2010-09-29
申请人： TRUSTEES OF TUFTS COLLEGE , WANG, Xiaoqin , KAPLAN, David L
发明人： WANG, Xiaoqin , KAPLAN, David L
IPC分类号： B82B3/00 , B82B1/00
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。包埋活性剂的丝状组合物还为被捕获的活性剂提供长期储存介质。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。

5. 发明申请

WO2011011347A2 FUNCTIONALIZATION OF SILK MATERIAL BY AVIDIN-BIOTIN INTERACTION 审中-公开
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：WO2011011347A2
公开(公告)日：2011-01-27
申请号：PCT/US2010/042502
申请日：2010-07-20
申请人： TRUSTEES OF TUFTS COLLEGE , KAPLAN, David L. , WANG, Xiaoqin , SERBAN, Monica A.
发明人： KAPLAN, David L. , WANG, Xiaoqin , SERBAN, Monica A.
IPC分类号： C07K14/435 , C07K19/00 , A61K47/48
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。

6. 发明公开

EP2211876A1 METHOD FOR SILK FIBROIN GELATION USING SONICATION 有权
标题翻译：方法利用超声SEIDENFIBROINGELIERUNG的
公开(公告)号：EP2211876A1
公开(公告)日：2010-08-04
申请号：EP08756432.4
申请日：2008-05-29
申请人： TRUSTEES OF TUFTS COLLEGE
发明人： WANG, Xiaoqin , KLUGE, Jon , LEISK, Gary, G. , KAPLAN, David, L.
IPC分类号： A61K35/24
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.

7. 发明公开

EP2841108A1 SILK MICROSPHERES AND METHODS FOR SURFACE LUBRICATION 审中-公开
标题翻译：丝绸微球和方法润滑面
公开(公告)号：EP2841108A1
公开(公告)日：2015-03-04
申请号：EP13780602.2
申请日：2013-04-25
申请人： Trustees of Tufts College , The Administrators of the Tulane Educational Fund
发明人： KAPLAN, David L. , WANG, Xiaoqin , JOHN, Vijay , PESIKA, Noshir , ZHENG, Rubo
IPC分类号： A61K47/42 , A61K47/30 , A61K9/16
CPC分类号： A61K47/42 , A61K9/1617 , A61K45/06 , A61L27/227 , A61L27/28 , A61L27/3645 , A61L27/50 , A61L27/54 , A61L2300/622 , A61L2400/10 , A61L2430/24
摘要： Provided herein relates to compositions and methods for lubrication of a surface. The surface amenable to the compositions and methods described herein can be a non-biological surface, a biological surface, or a combination thereof. In some embodiments, the composition comprising a phospholipid-coated silk microsphere can be used for lubrication of a surface. In some embodiments, the composition comprising a phospholipid-coated silk microsphere can be used for joint lubrication, e.g., for treatment of joint disorders such as arthritis.

8. 发明申请

WO2013155404A1 METHODS AND COMPOSITIONS FOR PREPARING A SILK MICROSPHERE 审中-公开
标题翻译：制备硅胶微球的方法和组合物
公开(公告)号：WO2013155404A1
公开(公告)日：2013-10-17
申请号：PCT/US2013/036356
申请日：2013-04-12
申请人： TRUSTEES OF TUFTS COLLEGE
发明人： KAPLAN, David L. , YUCEL, Tuna , WANG, Xiaoqin , LOVETT, Michael
IPC分类号： A61K47/42 , A61K47/30 , A61K9/16 , A61K9/14
CPC分类号： A61K9/1682 , A61K9/0019 , A61K9/1617 , A61K9/1658 , A61K31/13 , A61K47/38 , C07K16/22
摘要： Provided herein relates to methods and compositions for preparing a silk microsphere and the resulting silk microsphere. In some embodiments, the methods and compositions described herein are all aqueous, which can be used for encapsulating an active agent in a silk microsphere, while maintaining activity of the active agent during processing. In some embodiments, the resulting silk microsphere can be used for sustained delivery of an active agent encapsulated therein.
摘要翻译：本文涉及用于制备丝微球和所得丝微球的方法和组合物。在一些实施方案中，本文所述的方法和组合物都是水性的，其可用于将活性剂包封在丝微球中，同时保持活性剂在加工过程中的活性。在一些实施方案中，所得的丝微球可用于持续递送包封在其中的活性剂。

9. 发明授权

EP2836236B1 METHODS AND COMPOSITIONS FOR PREPARING A SILK MICROSPHERE 无效
公开(公告)号：EP2836236B1
公开(公告)日：2019-01-02
申请号：EP13775182.2
申请日：2013-04-12
申请人： Trustees Of Tufts College
发明人： KAPLAN, David L. , YUCEL, Tuna , WANG, Xiaoqin , LOVETT, Michael
IPC分类号： A61K47/42 , A61K47/30 , A61K9/16 , A61K9/14 , A61K9/00 , A61K47/38 , A61K31/13 , C07K16/22

10. 发明公开

EP2827884A1 SILK RESERVOIRS FOR DRUG DELIVERY 审中-公开
标题翻译：药物递送丝绸水库
公开(公告)号：EP2827884A1
公开(公告)日：2015-01-28
申请号：EP13764579.2
申请日：2013-03-11
申请人： Trustees of Tufts College
发明人： KAPLAN, David L. , YUCEL, Tuna , LOVETT, Michael L. , WANG, Xiaoqin
IPC分类号： A61K38/17 , A61K38/16 , A61K47/48 , A61K9/16
CPC分类号： A61K9/0024 , A61K9/0019 , A61K9/0092 , A61K9/4825 , A61K9/5052 , A61K31/00 , A61K31/13 , A61K31/5415
摘要： The present invention is directed to silk-based drug delivery compositions for controlled, sustained delivery of therapeutic agent(s) as well as methods of making and using the same.
摘要翻译：本发明涉及用于受控，持续递送治疗剂的丝基药物递送组合物及其制备和使用方法。

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