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1. 发明授权

US06596267B1 Methods and compositions to prevent formation of adhesions in biological tissues 失效
标题翻译：防止生物组织粘连形成的方法和组合物
公开(公告)号：US06596267B1
公开(公告)日：2003-07-22
申请号：US09140781
申请日：1998-08-27
申请人： Jeffrey A. Hubbell , Natalie D. Winblade , Donald L. Elbert
发明人： Jeffrey A. Hubbell , Natalie D. Winblade , Donald L. Elbert
IPC分类号： A61K3180
CPC分类号： A61L31/06 , A61K31/77 , A61K31/78 , A61K31/79 , A61K31/80 , A61L27/34 , A61L31/10 , Y10S525/937 , Y10S977/931 , C08L71/02 , C08L101/02
摘要： The invention discloses materials that adsorb readily to the surfaces of body tissues in situ and provide a steric barrier between such tissues, so that tissue adhesions, which typically form following surgical procedures, are minimized. These materials contain a polymer of hydrophilic molecules such as polyethylene glycol (PEG) bound to a polymer that spontaneously adsorbs to biological tissue such as phenylboronic acid (PBA). The PEG-PBA co-polymer can be formed in a variety of geometries. The materials can also be used to coat prosthetics and other implants.
摘要翻译：本发明公开了容易吸附到身体组织表面的材料，并且在这些组织之间提供空间屏障，使得通常形成以下外科手术的组织粘连最小化。这些材料包含亲水性分子的聚合物，例如与自发吸附到生物组织如苯硼酸（PBA）的聚合物结合的聚乙二醇（PEG）。 PEG-PBA共聚物可以以各种几何形状形成。这些材料也可用于涂覆假体和其他植入物。

2. 发明授权

US07029688B2 Methods and compositions to prevent formation of adhesions in biological tissues 失效
公开(公告)号：US07029688B2
公开(公告)日：2006-04-18
申请号：US10403344
申请日：2003-03-28
申请人： Jeffrey A. Hubbell , Natalie D. Winblade , Donald L. Elbert
发明人： Jeffrey A. Hubbell , Natalie D. Winblade , Donald L. Elbert
IPC分类号： A61P2/02 , A61P17/02 , A61P29/00 , A61P35/00 , A61K47/30
CPC分类号： A61L31/06 , A61K31/77 , A61K31/78 , A61K31/79 , A61K31/80 , A61L27/34 , A61L31/10 , Y10S525/937 , Y10S977/931 , C08L71/02 , C08L101/02
摘要： The invention discloses materials that adsorb readily to the surfaces of body tissues in situ and provide a steric barrier between such tissues, so that tissue adhesions, which typically form following surgical procedures, are minimized. These materials contain a polymer of hydrophilic molecules such as polyethylene glycol (PEG) bound to a polymer that spontaneously adsorbs to biological tissue such as phenylboronic acid (PBA). The PEG-PBA co-polymer can be formed in a variety of geometries. The materials can also be used to coat prosthetics and other implants.

3. 发明授权

US06652902B2 Gels and multilayer surface structures from boronic acid containing polymers 有权
公开(公告)号：US06652902B2
公开(公告)日：2003-11-25
申请号：US10035625
申请日：2001-12-28
申请人： Jeffrey A. Hubbell , Donald L. Elbert , Natalie D. Winblade
发明人： Jeffrey A. Hubbell , Donald L. Elbert , Natalie D. Winblade
IPC分类号： B05D300
CPC分类号： A61L31/10 , A61L27/34 , A61L29/085 , C08L71/02
摘要： Boronic acid containing polymers are used to form bioinert gels and multilayer surface structures. These polymers form crosslinked hydrogels, which are highly swollen in water. The crosslinking can either be chemical or physical. Water soluble polymers containing boronic acid groups, such as phenylboronic acid (PBA), can be physically crosslinked by mixing the polymers in water with other polymers containing hydroxyls or carboxylic acids. Alternatively, surfaces can be treated by stepwise incubation with a solution of the boronic acid containing polymer, followed by incubation with a solution of a diol or carboxylic acid containing polymer. Many successive layers can be generated, increasing the thickness of the formed structure at each step. The bioinert gel or surface coating can be used for passivating the surfaces of medical implants (especially those based on transplanted tissue), or for passivating the surfaces of tissues in situ, decreasing the incidence or severity of such pathologic conditions as the formation of post-surgical adhesions, and thrombosis following angioplasty.

4. 发明授权

US06350527B1 Gels and multilayer surface structures from boronic acid containing polymers 有权
标题翻译：含有硼酸的聚合物的凝胶和多层表面结构
公开(公告)号：US06350527B1
公开(公告)日：2002-02-26
申请号：US09384888
申请日：1999-08-27
申请人： Jeffrey A. Hubbell , Donald L. Elbert , Natalie D. Winblade
发明人： Jeffrey A. Hubbell , Donald L. Elbert , Natalie D. Winblade
IPC分类号： B32B904
CPC分类号： A61L31/10 , A61L27/34 , A61L29/085 , C08L71/02
摘要： Boronic acid containing polymers are used to form bioinert gels and multilayer surface structures. These polymers form crosslinked hydrogels, which are highly swollen in water. The crosslinking can either be chemical or physical. Water soluble polymers containing boronic acid groups, such as phenylboronic acid (PBA), can be physically crosslinked by mixing the polymers in water with other polymers containing hydroxyls or carboxylic acids. Alternatively, surfaces can be treated by stepwise incubation with a solution of the boronic acid containing polymer, followed by incubation with a solution of a diol or carboxylic acid containing polymer. Many successive layers can be generated, increasing the thickness of the formed structure at each step. The bioinert gel or surface coating can be used for passivating the surfaces of medical implants (especially those based on transplanted tissue), or for passivating the surfaces of tissues in situ.
摘要翻译：含硼酸的聚合物用于形成生物凝胶和多层表面结构。这些聚合物形成在水中高度溶胀的交联水凝胶。交联可以是化学或物理的。含有硼酸基团的水溶性聚合物如苯基硼酸（PBA）可通过将水中的聚合物与含有羟基或羧酸的其它聚合物混合而物理交联。或者，可以通过与含硼酸的聚合物的溶液逐步温育，然后与含二醇或含羧酸的聚合物的溶液温育来处理表面。可以产生许多连续的层，从而在每个步骤增加形成的结构的厚度。生物测定凝胶或表面涂层可用于钝化医疗植入物（特别是基于移植组织的植入物）表面，或用于钝化组织表面的原位。

5. 发明授权

US06884628B2 Multifunctional polymeric surface coatings in analytic and sensor devices 有权
标题翻译：分析和传感器设备中的多功能聚合物表面涂层
公开(公告)号：US06884628B2
公开(公告)日：2005-04-26
申请号：US09560472
申请日：2000-04-28
申请人： Jeffrey A. Hubbell , Marcus Textor , Donald L. Elbert , Stephanie Finken , Rolf Hofer , Nicholas D. Spencer , Laurence Ruiz-Taylor
发明人： Jeffrey A. Hubbell , Marcus Textor , Donald L. Elbert , Stephanie Finken , Rolf Hofer , Nicholas D. Spencer , Laurence Ruiz-Taylor
IPC分类号： A61L27/34 , A61L31/10 , G01N33/543 , G01N33/551 , G01N33/53
CPC分类号： B82Y30/00 , A61B5/14546 , A61B5/1459 , A61L27/34 , A61L31/10 , G01N33/54373 , G01N33/54393 , G01N33/551 , Y10S435/815 , Y10S435/961 , Y10S435/969 , Y10S436/819 , Y10S436/823
摘要： Multifunctional, polyionic copolymers with molecular architectures and properties optimized for specific applications are synthesized on/or applied to substrate surfaces for analytical and sensing purposes. The coatings are particularly useful for suppression of non-specific interaction, adsorption or attachment of molecular or ionic components present in an analyte solution. Chemical, biochemical or biological groups that are able to recognize, interact with and bind specifically to target molecules in the material containing the analyte to be detected can be coupled to, integrated into, or absorbed to the multifunctional copolymers. These multifunctional copolymer coatings are compatible with a variety of different established methods to detect, sense and quantify the target molecule in an analyte. The multifunctional copolymer coatings typically include brush copolymers based on a polycationic or polyanionic (jointly referred to herein as ‘polyionic’) backbone with side chains that control interaction with the environment, such as poly(ethylene glycol) or poly(ethylene oxide)-based side chains that decrease cellular adhesion, and analyte-specific side chains. They can be used to pattern the surfaces into non-adhesive and specifically adhesive areas by applications of known techniques such as microfluidic or contact printing techniques.
摘要翻译：具有分子结构和针对特定应用优化的性能的多功能聚异戊二烯共聚物在/或应用于基材表面进行合成，用于分析和感测目的。涂层对于抑制分析物溶液中存在的分子或离子组分的非特异性相互作用，吸附或附着是特别有用的。能够识别，相互作用并且特异性结合含有待检测分析物的物质中的靶分子的化学，生物化学或生物学基团可与多功能共聚物偶联，整合或吸收。这些多功能共聚物涂层与各种不同的已知方法兼容，以检测，感测和定量分析物中的目标分子。多功能共聚物涂层通常包括基于聚阳离子或聚阴离子（共同称为“聚阴离子”）骨架的刷共聚物，侧链具有控制与环境相互作用的侧链，例如聚（乙二醇）或聚（环氧乙烷）减少细胞粘附的侧链和分析物特异性侧链。它们可用于通过已知技术如微流体或接触印刷技术的应用将表面图案化成非粘合性和特异性粘合剂区域。

6. 发明授权

US06387977B1 Redox and photoinitiator systems for priming for improved adherence of gels to substrates 有权
标题翻译：氧化还原和光引发剂体系，用于引发凝胶以增强凝胶对底物的粘附性
公开(公告)号：US06387977B1
公开(公告)日：2002-05-14
申请号：US09616256
申请日：2000-07-14
申请人： Amarpreet S. Sawhney , David A. Melanson , Chandrashekar P. Pathak , Jeffrey A. Hubbell , Luis Z. Avila , Mark T. Kieras , Stephen D. Goodrich , Shikha P. Barman , Arthur J. Coury , Ronald S. Rudowsky , Douglas J. K. Weaver , Marc A. Levine , John C. Spiridigliozzi , Thomas S. Bromander , Dean M. Pichon , George Selecman , David J. Nedder , Bradley C. Poff , Donald L. Elbert
发明人： Amarpreet S. Sawhney , David A. Melanson , Chandrashekar P. Pathak , Jeffrey A. Hubbell , Luis Z. Avila , Mark T. Kieras , Stephen D. Goodrich , Shikha P. Barman , Arthur J. Coury , Ronald S. Rudowsky , Douglas J. K. Weaver , Marc A. Levine , John C. Spiridigliozzi , Thomas S. Bromander , Dean M. Pichon , George Selecman , David J. Nedder , Bradley C. Poff , Donald L. Elbert
IPC分类号： C09D400
CPC分类号： C09D4/00 , A61B17/00491 , A61B17/085 , A61B2017/00495 , A61L24/0015 , A61L24/0031 , A61L24/0042 , A61L24/046 , A61L24/06 , A61L2300/00 , C08F2/48 , C08F265/04 , C08F271/00 , C08F283/00 , C08F289/00 , C08F290/06 , C08F290/062 , C08F290/14 , C08F291/00 , C08L2666/02 , C09J151/00 , Y10S602/904 , C08L71/02 , C08L33/04 , C08F220/00
摘要： An impoved barrier or drug delivery system which is highly adherent to the surface to which it is applied is disclosed, along with methods for making the barrier. In the preferred embodiment, tissue is stained with a photoinitiator, then the polymer solution or gel having added thereto a defined amount of the same or a different photoinitiator is applied to the tissue. On exposure to light, the resulting system polymerizes at the surface, giving excellent adherence, and also forms a gel in the rest of the applied volume. Thus a gel barrier of arbitrary thickness can be applied to a surface while maintaining high adherence at the interface. This process is referred to herein as “priming”. The polymerizable barrier materials are highly useful for sealing tissue surfaces and junctions against leaks of fluids. In another embodiment, “priming” can be used to reliably adhere preformed barriers to tissue or other surfaces, or to adhere tissue surfaces to each other. A first surface and a barrier, or another surface, are prestained with initiator, and a thin layer of gelable monomer containing initiator is placed between them. Strong adhesion is obtained between the two surfaces on gelation of the monomer. In a similar fashion, tissue surfaces can be adhered to each other in repair of wounds and formation of anastomoses. Methods for use of non-photochemical systems and combined chemical/photochemical systems are described.
摘要翻译：公开了一种与其所施加的表面高粘附性的经阻挡或药物递送系统，以及用于制备屏障的方法。在优选的实施方案中，用光引发剂对组织进行染色，然后将向其中加入定量的相同或不同的光引发剂的聚合物溶液或凝胶施加到组织上。在暴露于光下时，所得体系在表面聚合，赋予优异的粘附性，并且在所施加的体积的其余部分中也形成凝胶。因此，可以在表面上施加任意厚度的凝胶屏障，同时在界面处保持高粘附性。该方法在本文中称为“起动”。可聚合的阻挡材料对于密封组织表面和防止流体泄漏的接头非常有用。在另一个实施例中，可以使用“起动”来将预先形成的障碍物可靠地粘附到组织或其它表面，或者将组织表面彼此附着。第一表面和屏障或另一个表面用引发剂预处理，并且在它们之间放置一层含有起泡剂的可凝胶单体。在单体凝胶化时，在两个表面之间获得强粘合性。以类似的方式，组织表面可以在伤口的修复和吻合的形成中彼此粘合。描述了使用非光化学体系和组合化学/光化学体系的方法。

7. 发明申请

US20090264538A1 MULTIFUNCTIONAL POLYMERIC TISSUE COATINGS 审中-公开
标题翻译：多功能聚合组织涂料
公开(公告)号：US20090264538A1
公开(公告)日：2009-10-22
申请号：US11927334
申请日：2007-10-29
申请人： Jeffrey A. Hubbell , Donald L. Elbert , Curtis B. Herbert
发明人： Jeffrey A. Hubbell , Donald L. Elbert , Curtis B. Herbert
IPC分类号： A61K47/42 , C07K2/00 , C08G63/91 , C08L5/00 , A61K47/36 , A61K47/30
CPC分类号： C08G81/00 , A61K9/10 , A61K9/5031 , A61K9/5073 , A61K31/00 , A61K47/34 , A61L27/34 , A61L31/10 , B33Y80/00 , Y10T428/31504 , Y10T428/31678 , Y10T428/31725 , Y10T428/31855 , Y10T428/31971
摘要： Compositions for coating biological and non-biological surfaces, which minimize or prevent cell-cell contact and tissue adhesion, and methods of preparation and use thereof are disclosed. Embodiments include polyethylene glycol/polylysine (PEG/PLL) block or comb-type copolymers with high molecular weight PLL (greater than 1000, more preferably greater than 100,000); PEG/PLL copolymers in which the PLL is a dendrimer which is attached to one end of the PEG; and multilayer compositions including alternating layers of polycationic and polyanionic materials. The multi-layer polymeric material is formed by the ionic interactions of a polycation and a polyanion. The molecular weights of the individual materials are selected such that the PEG portion of the copolymer inhibits cellular interactions, and the PLL portion adheres well to tissues. The compositions and methods are useful, for example, in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells. The compositions and methods are also useful for coating non-biological surfaces such as metallic surfaces.
摘要翻译：公开了用于涂覆生物和非生物表面的组合物，其最小化或防止细胞 - 细胞接触和组织粘附，以及其制备和使用方法。实施方案包括具有高分子量PLL（大于1000，更优选大于100,000）的聚乙二醇/聚赖氨酸（PEG / PLL）嵌段或梳型共聚物; PEG / PLL共聚物，其中PLL是连接到PEG的一端的树枝状大分子; 以及包括聚阳离子和聚阴离子材料的交替层的多层组合物。多层聚合物材料通过聚阳离子和聚阴离子的离子相互作用形成。选择各种材料的分子量使得共聚物的PEG部分抑制细胞相互作用，并且PLL部分粘附到组织上。组合物和方法可用于例如抑制手术后粘连的形成，保护受损的血管免受血栓形成和再狭窄，以及降低附着依赖性肿瘤细胞的转移程度。组合物和方法也可用于涂覆非生物表面如金属表面。

8. 发明授权

US06743521B2 Multifunctional polymeric tissue coatings 失效
标题翻译：多功能聚合物组织涂层
公开(公告)号：US06743521B2
公开(公告)日：2004-06-01
申请号：US09403428
申请日：2000-01-06
申请人： Jeffrey A. Hubbell , Donald L. Elbert , Curtis B. Herbert
发明人： Jeffrey A. Hubbell , Donald L. Elbert , Curtis B. Herbert
IPC分类号： B32B1800
CPC分类号： C08G81/00 , A61K9/10 , A61K9/5031 , A61K9/5073 , A61K31/00 , A61K47/34 , A61L27/34 , A61L31/10 , B33Y80/00 , Y10T428/31504 , Y10T428/31678 , Y10T428/31725 , Y10T428/31855 , Y10T428/31971
摘要： Compositions for coating biological and non-biological surfaces, which minimize or prevent cell-cell contact and tissue adhesion, and methods of preparation and use thereof, are disclosed. Embodiments include polyethylene glycol/polylysine (PEG/PLL) block or comb-type copolymers with high molecular weight PLL (greater than 1000, more preferably greater than 100,000); PEG/PLL copolymers in which the PLL is a dendrimer which is attached to one end of the PEG; and multilayer compositions including alternating layers of polycationic and polyanionic materials. The multi-layer polymeric material is formed by the ionic interactions of a polycation and a polyanion. The molecular weights of the individual materials are selected such that the PEG portion of the copolymer inhibits cellular interactions, and the PLL portion adheres well to tissues. The compositions and methods are useful, for example, in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells. The compositions and methods are also useful for coating non-biological surfaces such as metallic surfaces.
摘要翻译：公开了用于涂覆生物和非生物表面的组合物，其最小化或防止细胞 - 细胞接触和组织粘附，以及其制备和使用方法。实施方案包括具有高分子量PLL（大于1000，更优选大于100,000）的聚乙二醇/聚赖氨酸（PEG / PLL）嵌段或梳型共聚物; PEG / PLL共聚物，其中PLL是连接到PEG的一端的树枝状大分子; 以及包括聚阳离子和聚阴离子材料的交替层的多层组合物。多层聚合物材料通过聚阳离子和聚阴离子的离子相互作用形成。选择各种材料的分子量使得共聚物的PEG部分抑制细胞相互作用，并且PLL部分粘附到组织上。组合物和方法可用于例如抑制手术后粘连的形成，保护受损的血管免受血栓形成和再狭窄，以及降低附着依赖性肿瘤细胞的转移程度。组合物和方法也可用于涂覆非生物表面如金属表面。

9. 发明授权

US07670605B2 Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds 有权
标题翻译：药物活性化合物受控输送的共轭加成反应
公开(公告)号：US07670605B2
公开(公告)日：2010-03-02
申请号：US12192655
申请日：2008-08-15
申请人： Jeffrey A. Hubbell , Donald L. Elbert , Ronald Schoenmakers
发明人： Jeffrey A. Hubbell , Donald L. Elbert , Ronald Schoenmakers
IPC分类号： A61K39/00 , C12Q1/68 , C12N9/96 , C07H21/04
CPC分类号： A61L27/52 , A61K47/60 , A61K47/6903 , C07H21/04 , C08G65/329 , C08G65/3322 , C12N5/0068 , C12N2501/585 , C12N2533/30
摘要： The invention features polymeric biomaterials formed by nucleophilic addition reactions to conjugated unsaturated groups. These biomaterials may be used for medical treatments.
摘要翻译：本发明的特征在于通过对共轭不饱和基团的亲核加成反应形成的聚合物生物材料。这些生物材料可用于医疗治疗。

10. 发明授权

US07316845B2 Multifunctional polymeric tissue coatings 有权
标题翻译：多功能聚合物组织涂层
公开(公告)号：US07316845B2
公开(公告)日：2008-01-08
申请号：US10804787
申请日：2004-03-19
申请人： Jeffrey A. Hubbell , Donald L. Elbert , Curtis B. Herbert
发明人： Jeffrey A. Hubbell , Donald L. Elbert , Curtis B. Herbert
IPC分类号： B32B15/04 , B32B17/06
CPC分类号： C08G81/00 , A61K9/10 , A61K9/5031 , A61K9/5073 , A61K31/00 , A61K47/34 , A61L27/34 , A61L31/10 , B33Y80/00 , Y10T428/31504 , Y10T428/31678 , Y10T428/31725 , Y10T428/31855 , Y10T428/31971
摘要： Compositions for coating biological and non-biological surfaces, which minimize or prevent cell-cell contact and tissue adhesion, and methods of preparation and use thereof, are disclosed. Embodiments include polyethylene glycol/polylysine (PEG/PLL) block or comb-type copolymers with high molecular weight PLL (greater than 1000, more preferably greater than 100,000); PEG/PLL copolymers in which the PLL is a dendrimer which is attached to one end of the PEG; and multilayer compositions including alternating layers of polycationic and polyanionic materials. The multi-layer polymeric material is formed by the ionic interactions of a polycation and a polyanion. The molecular weights of the individual materials are selected such that the PEG portion of the copolymer inhibits cellular interactions, and the PLL portion adheres well to tissues. The compositions and methods are useful, for example, in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells. The compositions and methods are also useful for coating non-biological surfaces such as metallic surfaces.
摘要翻译：公开了用于涂覆生物和非生物表面的组合物，其最小化或防止细胞 - 细胞接触和组织粘附，以及其制备和使用方法。实施方案包括具有高分子量PLL（大于1000，更优选大于100,000）的聚乙二醇/聚赖氨酸（PEG / PLL）嵌段或梳型共聚物; PEG / PLL共聚物，其中PLL是连接到PEG的一端的树枝状大分子; 以及包括聚阳离子和聚阴离子材料的交替层的多层组合物。多层聚合物材料通过聚阳离子和聚阴离子的离子相互作用形成。选择各种材料的分子量使得共聚物的PEG部分抑制细胞相互作用，并且PLL部分粘附到组织上。组合物和方法可用于例如抑制手术后粘连的形成，保护受损的血管免受血栓形成和再狭窄，以及降低附着依赖性肿瘤细胞的转移程度。组合物和方法也可用于涂覆非生物表面如金属表面。

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