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1. 发明申请

US20080182909A1 METHODS FOR STABILIZING BIOLOGICALLY ACTIVE AGENTS ENCAPSULATED IN BIODEGRADABLE CONTROLLED-RELEASE POLYMERS 审中-公开
标题翻译：用于稳定可生物降解控制释放聚合物中生物活性剂的方法
公开(公告)号：US20080182909A1
公开(公告)日：2008-07-31
申请号：US11863088
申请日：2007-09-27
申请人： Steven P. Schwendeman , Gaozhong Zhu , Hanne Bentz , Jeffrey A. Hubbell , Wenlei Jiang , Anna Shenderova , Jichao Kang
发明人： Steven P. Schwendeman , Gaozhong Zhu , Hanne Bentz , Jeffrey A. Hubbell , Wenlei Jiang , Anna Shenderova , Jichao Kang
IPC分类号： A61K47/30
CPC分类号： A61K9/1647 , A61K9/0019 , A61K47/02
摘要： Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.
摘要翻译：提供了用于减少或抑制在可生物降解的聚合物递送系统中的水溶性生物活性剂的不可逆失活的方法，其被设计为在长时间内释放这些试剂，例如PLGA递送系统。该方法包括制备PLGA递送系统，其微生物即活性剂所在的孔在生物降解过程中均匀或均匀地保持3至9之间，优选4至8，更优选5至7.5之间的pH。根据输送系统的尺寸和聚合物的初始体积渗透性，该结果通过（a）将水溶性载体引入输送系统来实现，（b）将选择的碱性添加剂（或抗酸剂）掺入递送系统，（c）将水溶性载体和选择性碱性添加剂并入输送系统中，（d）添加成孔分子，以将低分子量单体和低聚物的释放速率提高到递送系统中（ e）使用具有降低的乙交酯含量的PLGA聚合物，即具有100％至75％丙交酯和0至25％乙交酯的PLGA）（f）使用产生更广泛孔隙网络的微胶囊化方法，例如油包水乳液 - 溶剂萃取相对于水包油型水溶剂蒸发法，和（g）它们的组合。

2. 发明授权

US06743446B2 Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers 失效
标题翻译：用于稳定包封在可生物降解的控释聚合物中的生物活性剂的方法
公开(公告)号：US06743446B2
公开(公告)日：2004-06-01
申请号：US09738961
申请日：2000-12-15
申请人： Steven P. Schwendeman , Gaozhong Zhu , Hanne Bentz , Jeffrey A. Hubbell , Wenlei Jiang , Anna Shenderova , Jichao Kang
发明人： Steven P. Schwendeman , Gaozhong Zhu , Hanne Bentz , Jeffrey A. Hubbell , Wenlei Jiang , Anna Shenderova , Jichao Kang
IPC分类号： A61K914
CPC分类号： A61K9/1647 , A61K9/0019 , A61K47/02
摘要： Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing a PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.
摘要翻译：提供了用于减少或抑制在可生物降解的聚合物递送系统中的水溶性生物活性剂的不可逆失活的方法，其被设计为在长时间内释放这些试剂，例如PLGA递送系统。该方法包括制备PLGA递送系统，其微生物即活性剂所在的孔在生物降解过程中均匀或均匀地保持在3至9之间，优选4至8之间，更优选5至7.5的pH。根据输送系统的尺寸和聚合物的初始体积渗透性，该结果通过（a）将水溶性载体引入输送系统来实现，（b）将选择的碱性添加剂（或抗酸剂）掺入递送系统，（c）将水溶性载体和选择性碱性添加剂并入输送系统中，（d）添加成孔分子，以将低分子量单体和低聚物的释放速率提高到递送系统中（ e）使用具有降低的乙交酯含量的PLGA聚合物，即具有100％至75％丙交酯和0至25％乙交酯的PLGA）（f）使用产生更广泛孔隙网络的微胶囊化方法，例如油包水乳液 - 溶剂萃取相对于水包油型水溶剂蒸发法，和（g）它们的组合。

3. 发明授权

US08323696B2 Nanoparticles for immunotherapy 有权
标题翻译：用于免疫治疗的纳米颗粒
公开(公告)号：US08323696B2
公开(公告)日：2012-12-04
申请号：US12231310
申请日：2008-08-29
申请人： Jeffrey A. Hubbell , Conlin P. O'Neil , Sai T. Reddy , Melody A. Swartz , Diana Velluto , André van der Vlies , Eleonora Simeoni
发明人： Jeffrey A. Hubbell , Conlin P. O'Neil , Sai T. Reddy , Melody A. Swartz , Diana Velluto , André van der Vlies , Eleonora Simeoni
IPC分类号： A61K9/14
CPC分类号： A61K9/5146 , A61K9/0034 , A61K9/006 , A61K38/19 , A61K39/0011 , A61K47/6907 , A61K47/6935 , A61K2039/6093 , B82Y5/00
摘要： Nanoparticles that activate complement in the absence of biological molecules are described. The nanoparticles are shown to specifically target antigen presenting cells in specifically in lymph nodes, without the use of a biological molecule for targeting. These particles are useful vehicles for delivering immunotherapeutics. Surface chemistries and chemical formulations for the nanoparticles are described.
摘要翻译：描述了在不存在生物分子的情况下激活补体的纳米颗粒。显示了纳米颗粒特异性靶向抗原呈递细胞，特别是在淋巴结中，而不用生物分子进行靶向。这些颗粒是用于递送免疫治疗剂的有用载体。描述了纳米颗粒的表面化学和化学配方。

4. 发明申请

US20110223217A1 BLOCK COPOLYMERS AND USES THEREOF 有权
标题翻译：嵌段共聚物及其用途
公开(公告)号：US20110223217A1
公开(公告)日：2011-09-15
申请号：US13130892
申请日：2009-11-24
申请人： James Brandon Dixon , Jeffrey A. Hubbell , Conlin P. O'Neil , Melody Swartz , Diana Velluto
发明人： James Brandon Dixon , Jeffrey A. Hubbell , Conlin P. O'Neil , Melody Swartz , Diana Velluto
IPC分类号： A61K47/34 , C08G75/14 , A61K31/56 , A61K31/337 , A61K38/13 , A61K31/436 , A61K31/7048 , A61K31/704 , A61K38/00 , A61K31/7052 , A61K39/395 , A61K9/00 , C12N15/00
CPC分类号： A61K48/0041 , A61K9/1075 , A61K9/1273 , A61K9/5146 , A61K31/337 , A61K31/573 , A61K31/713 , A61K47/10 , A61K47/22 , A61K47/34 , C07K16/00 , C08G65/329 , C08G65/3344 , C08G75/08 , C08G83/008 , C08L71/02 , C08L81/02 , C08L2203/02 , C08L2205/05 , C12N15/113 , C12N15/115 , C12N2310/11 , C12N2310/14 , C12N2310/141 , C12N2310/16 , C12N2320/32 , Y02A50/387 , Y10S977/773 , Y10S977/906 , Y10S977/916 , C08L81/00
摘要： An encoding/decoding apparatus and method using a low-density parity-check code (LDPC code) is disclosed. Basic column group information, serving as a set of information regarding positions of rows with weight 1, is extracted from a reference column in each column group of a predetermined parity-check matrix. Column group information transforms the positions of rows with weight 1 into positions whose lengths are within a required parity length. A parity-check matrix is generated according to the generated column group information. Data is encoded or decoded based on the generated parity-check matrix.
摘要翻译：公开了一种使用低密度奇偶校验码（LDPC码）的编码/解码装置和方法。从预定奇偶校验矩阵的每列组中的参考列中提取用作关于具有权重1的行的位置的信息集合的基本列组信息。列组信息将具有权重1的行的位置变换为长度在所需奇偶校验长度内的位置。根据生成的列组信息生成奇偶校验矩阵。基于生成的奇偶校验矩阵对数据进行编码或解码。

5. 发明申请

US20100080850A1 POLYPEPTIDE LIGANDS FOR TARGETING CARTILAGE AND METHODS OF USE THEREOF 审中-公开
标题翻译：用于靶向治疗的多肽配体及其使用方法
公开(公告)号：US20100080850A1
公开(公告)日：2010-04-01
申请号：US12563201
申请日：2009-09-21
申请人： Jeffrey A. Hubbell , Dominique A. Rothenfluh
发明人： Jeffrey A. Hubbell , Dominique A. Rothenfluh
IPC分类号： A61K9/14 , C07K7/06 , C07K7/08 , C07K14/00 , C07H21/00 , C12N15/74 , A61K38/08 , A61K38/10 , A61K38/16 , A61P19/02
CPC分类号： C07K7/06
摘要： Ligands that specifically bind to articular cartilage tissues are disclosed, including uses for targeting therapeutics towards articular cartilage tissue and new materials for articular cartilage. The ligands are effective in vivo to target therapeutic materials to articular cartilage.
摘要翻译：公开了特异性结合关节软骨组织的配体，包括用于将治疗剂靶向关节软骨组织的用途和用于关节软骨的新材料。配体在体内是有效的，以将治疗材料靶向关节软骨。

6. 发明申请

US20080274201A1 GELS FOR ENCAPSULATION OF BIOLOGICAL MATERIALS 审中-公开
标题翻译：凝胶生物材料的凝胶
公开(公告)号：US20080274201A1
公开(公告)日：2008-11-06
申请号：US12172063
申请日：2008-07-11
申请人： Jeffrey A. Hubbell , Chandrashekhar P. Pathak , Amarpreet S. Sawhney , Neil P. Desai , Syed F.A. Hossainy
发明人： Jeffrey A. Hubbell , Chandrashekhar P. Pathak , Amarpreet S. Sawhney , Neil P. Desai , Syed F.A. Hossainy
IPC分类号： C12N11/04 , C08F2/46 , C08G59/02 , C08G65/02 , A61L33/06 , A61L33/08 , A61L33/12 , A61L33/16 , C08G73/00 , C08K5/04 , C08K5/16 , A61K9/50 , C08K5/07 , C08K5/34
CPC分类号： A61K9/5073 , A61K9/5031 , A61K47/60 , A61K47/645 , A61K47/6925
摘要： This invention provides novel methods for the formation of biocompatible membranes around biological materials using photopolymerization of water soluble molecules. The membranes can be used as a covering to encapsulate biological materials or biomedical devices, as a “glue” to cause more than one biological substance to adhere together, or as carriers for biologically active species. Several methods for forming these membranes are provided. Each of these methods utilizes a polymerization system containing water-soluble macromers, species, which are at once polymers and macromolecules capable of further polymerization. The macromers are polymerized using a photoinitiator (such as a dye), optionally a cocatalyst, optionally an accelerator, and radiation in the form of visible or long wavelength UV light. The reaction occurs either by suspension polymerization or by interfacial polymerization. The polymer membrane can be formed directly on the surface of the biological material, or it can be formed on material, which is already encapsulated.
摘要翻译：本发明提供了使用水溶性分子的光聚合在生物材料周围形成生物相容性膜的新方法。该膜可以用作包封生物材料或生物医学装置的覆盖物，作为使胶粘剂引起不止一种生物物质粘附在一起，或作为生物活性物质的载体。提供了形成这些膜的几种方法。这些方法中的每一种都使用含有水溶性大分子单体的聚合体系，它们是能够进一步聚合的聚合物和大分子。大分子单体使用光引发剂（例如染料），任选的助催化剂，任选的促进剂和可见或长波长UV光的形式的辐射聚合。该反应通过悬浮聚合或通过界面聚合进行。聚合物膜可以直接形成在生物材料的表面上，或者可以在已经被包封的材料上形成。

7. 发明授权

US07427410B2 Coating hydrophobic surfaces with amphiphilic thioethers to reduce protein adsorption and cell adhesion 有权
标题翻译：用两亲性硫醚涂覆疏水表面以减少蛋白质吸附和细胞粘附
公开(公告)号：US07427410B2
公开(公告)日：2008-09-23
申请号：US10246362
申请日：2002-09-18
申请人： Jeffrey A. Hubbell , Jane P. Bearinger , Alessandro Napoli , Marcus Textor , Nicola Tirelli
发明人： Jeffrey A. Hubbell , Jane P. Bearinger , Alessandro Napoli , Marcus Textor , Nicola Tirelli
IPC分类号： A61F2/00 , A61K38/43 , C12N11/08
CPC分类号： A61L27/34 , C08L81/02
摘要： The present invention provides methods and apparatus for coating surfaces with specially designed thioethers and amphiphilic thioethers that reduce protein adsorption and/or cell adhesion. This reduction may be achieved, for example, by controlling the spacing or length of pendant chains or hydrophilic blocks in an amphiphilic thioether. Techniques for determining spacing include adsorbing the thioether from a solution or a colloidal suspension, or controlling the degree of polymerization of the thioether. Techniques for controlling the length of the pendant chains include controlling the degree of polymerization of the pendant chains. Multiblock copolymers of poly(propylene sulfide) and poly(ethylene glycol) (“PPS-PEG”) represent an exemplary family of amphiphilic thioethers. Methods for coating surfaces with amphiphilic thioethers are also provided.
摘要翻译：本发明提供了用特别设计的硫醚和两亲性硫醚涂覆表面的方法和设备，其减少蛋白质吸附和/或细胞粘附。该还原可以通过例如通过控制两亲性硫醚中的侧链或亲水嵌段的间隔或长度来实现。用于确定间隔的技术包括从溶液或胶体悬浮液中吸附硫醚，或控制硫醚的聚合度。用于控制侧链长度的技术包括控制侧链的聚合度。聚（丙烯硫醚）和聚（乙二醇）（“PPS-PEG”）的多嵌段共聚物代表两亲性硫醚的典型族。还提供了用两亲硫醚涂覆表面的方法。

8. 发明授权

US07247609B2 Growth factor modified protein matrices for tissue engineering 有权
标题翻译：用于组织工程的生长因子修饰蛋白质基质
公开(公告)号：US07247609B2
公开(公告)日：2007-07-24
申请号：US10325021
申请日：2002-12-18
申请人： Matthias Lütolf , Jason Schense , Jeffrey A. Hubbell , Anna Jen
发明人： Matthias Lütolf , Jason Schense , Jeffrey A. Hubbell , Anna Jen
IPC分类号： A01N37/18
CPC分类号： A61L27/225 , A61K38/00 , A61L27/227 , C07K14/635 , C07K2319/00
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.
摘要翻译：将蛋白质掺入用于组织修复，再生和/或重塑和/或药物递送的蛋白质或多糖基质中。可以掺入蛋白质，使其通过降解基质，通过酶作用和/或扩散来释放。如实施例所示，一种方法是通过共价或非共价方法将肝素与基质结合，形成肝素基质。然后肝素将肝素结合生长因子非共价结合到蛋白质基质上。或者，可以构建融合蛋白，其包含交联区域，例如因子XIIIa底物和天然蛋白质序列。当需要长期药物递送时，例如在神经再生的情况下，在基质和生物活性因子之间引入可降解的键可能是特别有用的，其中期望在空间上改变作为再生的功能的药物释放速率，例如快速靠近生物组织界面，并进一步向进入损伤区更慢。额外的益处包括递送系统内的总药物剂量越少，释放的空间调节，允许在最大的细胞活动时释放更多百分比的药物。

9. 发明授权

US06960452B2 Enzyme-mediated modification of fibrin for tissue engineering: incorporation of proteins 有权
标题翻译：酶介导的纤维蛋白修饰组织工程：掺入蛋白质
公开(公告)号：US06960452B2
公开(公告)日：2005-11-01
申请号：US09798338
申请日：2001-03-02
申请人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama
发明人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama
IPC分类号： C07K14/475 , C12P21/00 , A01N1/00 , A61K9/14
CPC分类号： C07K14/475
摘要： Disclosed are materials that may be used in the design of improved devices and wound treatment platforms though covalent and/or non-covalent attachment of bioactive proteins. The proteins comprise any variety of cell growth and/or healing promoting proteins, such as growth factor. The incorporation of these whole proteins may be designed to provide controlled release thereof in a biological system through further use of enzyme degradation sites. Heparin-binding protein or fusion proteins synthesized to contain a heparin-binding domain are two mechanisms that may be used in providing these properties to a matrix, such as a fibrinogen matrix. The proteins will be used to provide enhanced healing in various tissues including vasculature, skin, nerve, and liver. The materials disclosed will be used to enhance would?? Healing and other generative processes by engineering the fibrin gel to contain appropriate proteins with specifically designed release and/or degradation characteristics.
摘要翻译：公开了可以用于设计改进的装置和伤口治疗平台的材料，尽管共价和/或非共价连接生物活性蛋白质。蛋白质包括任何多种细胞生长和/或愈合促进蛋白质，例如生长因子。可以将这些全蛋白的掺入设计成通过进一步使用酶降解位点来提供其在生物系统中的受控释放。合成含有肝素结合结构域的肝素结合蛋白或融合蛋白是可用于向基质例如纤维蛋白原基质提供这些性质的两种机制。蛋白质将用于在各种组织中提供增强的愈合，包括脉管系统，皮肤，神经和肝脏。所披露的材料将被用来增强通过设计纤维蛋白凝胶来包含具有专门设计的释放和/或降解特性的合适蛋白质来治疗和其他生成过程。

10. 发明授权

US06894022B1 Growth factor modified protein matrices for tissue engineering 有权
标题翻译：用于组织工程的生长因子修饰蛋白质基质
公开(公告)号：US06894022B1
公开(公告)日：2005-05-17
申请号：US09563760
申请日：2000-05-01
申请人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama-Elbert
发明人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama-Elbert
IPC分类号： C07K14/475 , A61K31/727
CPC分类号： C07K14/475
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling, and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, enzymatic action, and/or diffusion. In one embodiment, a fusion protein, which contains a crosslinking region, such as a factor XIIIa substrate, and a native protein sequence, such as a bioactive factor, is constructed. Degradable linkages may be included between the crosslinking region and the bioactive factor.
摘要翻译：将蛋白质掺入用于组织修复，再生和/或重塑和/或药物递送的蛋白质或多糖基质中。可以掺入蛋白质，使其通过降解基质，酶作用和/或扩散而释放。在一个实施方案中，构建了含有交联区域（例如因子XIIIa底物）和天然蛋白质序列（例如生物活性因子）的融合蛋白质。交联区域和生物活性因子之间可以包括可降解的连接。

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