公开(公告)号：US07176256B2

公开(公告)日：2007-02-13

申请号：US10873833

申请日：2004-06-21

申请人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

发明人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

IPC分类号： C08F283/00 ,  C08G63/02 ,  C08G63/91 ,  C08G69/48 ,  C08L89/00 ,  A61K31/74 ,  A61K31/785 ,  A61K47/48

CPC分类号： A61L31/16 ,  A61L24/043 ,  A61L24/08 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/041 ,  A61L2300/232 ,  A61L2300/252 ,  A61L2300/606 ,  C08B37/0075 ,  C08G65/329 ,  C08H1/00 ,  C08H1/06 ,  C08L71/02 ,  Y10S623/90 ,  Y10S623/901 ,  C08L5/16 ,  C08L71/00

摘要： Crosslinked polymer compositions comprise a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (—NH2)or thiol (—SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer which contains, or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further comprise other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents. Also disclosed are methods for using the crosslinked polymmer compositions to effect adhesion between a first surface and a second surface; to effect tissue augmentation; to prevent the formation of surgical adhesions; and to coat a surface of a synthetic implant.

摘要翻译： 交联聚合物组合物包含含有多个亲核基团的第一合成聚合物，其共价键合到含有多个亲电子基团的第二合成聚合物。 第一合成聚合物优选是已经被修饰以含有多个亲核基团的合成多肽或聚乙二醇，例如伯氨基（-NH 2）或硫醇（-SH）基团。 第二合成聚合物可以是亲水或疏水的合成聚合物，其包含或已被衍生化以含有两个或更多个亲电基团，例如琥珀酰亚胺基。 组合物还可以包含其它组分，例如天然存在的多糖或蛋白质（例如糖胺聚糖或胶原）和/或生物活性剂。 还公开了使用交联聚合物组合物来实现第一表面和第二表面之间的粘合的方法; 进行组织增生; 防止手术粘连的形成; 并涂覆合成植入物的表面。

公开(公告)号：US6096309A

公开(公告)日：2000-08-01

申请号：US99126

申请日：1998-06-17

申请人： Jeffrey J. Prior ,  Donald G. Wallace ,  David H. Sierra ,  Frank A. DeLustro

发明人： Jeffrey J. Prior ,  Donald G. Wallace ,  David H. Sierra ,  Frank A. DeLustro

IPC分类号： A61L24/00 ,  A61K38/17 ,  A61K38/46 ,  A61L24/04 ,  A61L24/10 ,  A61P7/04 ,  A61K38/00

CPC分类号： A61L24/106 ,  A61L24/043 ,  A61L24/102 ,  A61L2400/04

摘要： The present invention relates to thrombin-containing hemostatic compositions, their preparation and use. In particular, it relates to hemostatic compositions comprising stabilized thrombin and microfibrillar collagen in an aqueous medium. In a preferred embodiment of the present invention, the compositions are used in a kit comprising two different components, one of which is autologous patient's plasma as the source of fibrinogen, and the other of which is the thrombin-containing composition which also contains microfibrillar collagen having an average diameter of about 3-30 nanometers.

摘要翻译： 本发明涉及含凝血酶的止血组合物，其制备和用途。 具体地说，本发明涉及在水性介质中包含稳定的凝血酶和微原纤维胶原的止血组合物。 在本发明的优选实施方案中，组合物用于包含两种不同组分的试剂盒中，其中一种是自体患者的血浆作为纤维蛋白原的来源，另一种是含有含有微​​原纤维胶原蛋白的凝血酶组合物 平均直径约为3-30纳米。

公开(公告)号：US06911496B2

公开(公告)日：2005-06-28

申请号：US10766726

申请日：2004-01-27

申请人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

发明人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

IPC分类号： A61K47/34 ,  A61L24/00 ,  A61L24/04 ,  A61L24/08 ,  A61L27/00 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/00 ,  A61L31/04 ,  A61L31/16 ,  A61L33/00 ,  C08B37/00 ,  C08G65/329 ,  C08G81/00 ,  C08H1/00 ,  C08H1/06 ,  C08L71/02 ,  C08L77/04 ,  C08L101/00 ,  C08F283/00 ,  C08G63/48 ,  C08G63/91 ,  C08L77/00

CPC分类号： A61L31/16 ,  A61L24/043 ,  A61L24/08 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/041 ,  A61L2300/232 ,  A61L2300/252 ,  A61L2300/606 ,  C08B37/0075 ,  C08G65/329 ,  C08H1/00 ,  C08H1/06 ,  C08L71/02 ,  Y10S623/90 ,  Y10S623/901 ,  C08L5/16 ,  C08L71/00

摘要： Provided are crosslinked polymer compositions that include a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (—NH2) or thiol (—SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer, which contains or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further include other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents. Also disclosed are methods for using the crosslinked polymer compositions to effect adhesion between a first surface and a second surface; to effect tissue augmentation; to prevent the formation of surgical adhesions; and to coat a surface of a synthetic implant.

摘要翻译： 提供的交联聚合物组合物包括含有共价结合到含有多个亲电子基团的第二合成聚合物的多个亲核基团的第一合成聚合物。 第一合成聚合物优选是已经被修饰以含有多个亲核基团的合成多肽或聚乙二醇，例如伯氨基（-NH 2）或硫醇（-SH）基团。 第二合成聚合物可以是亲水或疏水的合成聚合物，其包含或已被衍生化为含有两个或多个亲电基团，例如琥珀酰亚胺基。 组合物还可包括其它组分，例如天然存在的多糖或蛋白质（例如糖胺聚糖或胶原）和/或生物活性剂。 还公开了使用交联聚合物组合物来实现第一表面和第二表面之间的粘合的方法; 进行组织增生; 防止手术粘连的形成; 并涂覆合成植入物的表面。

公开(公告)号：US06323278B2

公开(公告)日：2001-11-27

申请号：US09733739

申请日：2000-12-08

申请人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

发明人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

IPC分类号： C08F28300

CPC分类号： A61L31/16 ,  A61L24/043 ,  A61L24/08 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/041 ,  A61L2300/232 ,  A61L2300/252 ,  A61L2300/606 ,  C08B37/0075 ,  C08G65/329 ,  C08H1/00 ,  C08H1/06 ,  C08L71/02 ,  Y10S623/90 ,  Y10S623/901 ,  C08L5/16 ,  C08L71/00

摘要： Crosslinked polymer compositions comprise a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (—NH2) or thiol (—SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer which contains, or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further comprise other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents. Also disclosed are methods for using the crosslinked polymer compositions to effect adhesion between a first surface and a second surface; to effect tissue augmentation; to prevent the formation of surgical adhesions; and to coat a surface of a synthetic implant.

摘要翻译： 交联聚合物组合物包含含有多个亲核基团的第一合成聚合物，其共价键合到含有多个亲电子基团的第二合成聚合物。 第一合成聚合物优选是已经被修饰以含有多个亲核基团的合成多肽或聚乙二醇，例如伯氨基（-NH 2）或硫醇（-SH）基团。 第二合成聚合物可以是亲水或疏水的合成聚合物，其包含或已被衍生化以含有两个或更多个亲电基团，例如琥珀酰亚胺基。 组合物还可以包含其它组分，例如天然存在的多糖或蛋白质（例如糖胺聚糖或胶原）和/或生物活性剂。 还公开了使用交联聚合物组合物来实现第一表面和第二表面之间的粘合的方法; 进行组织增生; 防止手术粘连的形成; 并涂覆合成植入物的表面。

公开(公告)号：US06280727B1

公开(公告)日：2001-08-28

申请号：US09436903

申请日：1999-11-09

申请人： Jeffrey J. Prior ,  Donald G. Wallace ,  David H. Sierra ,  Frank A. DeLustro

发明人： Jeffrey J. Prior ,  Donald G. Wallace ,  David H. Sierra ,  Frank A. DeLustro

IPC分类号： A61K3800

CPC分类号： A61L24/106 ,  A61L24/043 ,  A61L24/102 ,  A61L2400/04 ,  C08L89/06

摘要： The present invention relates to thrombin-containing hemostatic compositions, their preparation and use. In particular, it relates to hemostatic compositions comprising stabilized thrombin and microfibrillar collagen in an aqueous medium. In a preferred embodiment of the present invention, the compositions are used in a kit comprising two different components, one of which is autologous patient's plasma as the source of fibrinogen, and the other of which is the thrombin-containing composition which also contains microfibrillar collagen.

摘要翻译： 本发明涉及含凝血酶的止血组合物，其制备和用途。 具体地说，本发明涉及在水性介质中包含稳定的凝血酶和微原纤维胶原的止血组合物。 在本发明的优选实施方案中，组合物用于包含两种不同组分的试剂盒中，其中一种是自体患者的血浆作为纤维蛋白原的来源，另一种是含有含有微​​原纤维胶原蛋白的凝血酶组合物 。

公开(公告)号：US5874500A

公开(公告)日：1999-02-23

申请号：US769806

申请日：1996-12-18

申请人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

发明人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

IPC分类号： A61K47/34 ,  A61L24/00 ,  A61L24/04 ,  A61L24/08 ,  A61L27/00 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/00 ,  A61L31/04 ,  A61L31/16 ,  A61L33/00 ,  C08B37/00 ,  C08G65/329 ,  C08G81/00 ,  C08H1/00 ,  C08H1/06 ,  C08L71/02 ,  C08L77/04 ,  C08L101/00 ,  C08F283/00 ,  C08G63/91 ,  C08G69/48

CPC分类号： A61L31/16 ,  A61L24/043 ,  A61L24/08 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/041 ,  C08B37/0075 ,  C08G65/329 ,  C08H1/00 ,  C08H1/06 ,  C08L71/02 ,  A61L2300/232 ,  A61L2300/252 ,  A61L2300/606 ,  Y10S623/90 ,  Y10S623/901

摘要： Crosslinked polymer compositions comprise a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (--NH.sub.2) or thiol (--SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer which contains, or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further comprise other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents. Also disclosed are methods for using the crosslinked polymer compositions to effect adhesion between a first surface and a second surface; to effect tissue augmentation; to prevent the formation of surgical adhesions; and to coat a surface of a synthetic implant.

公开(公告)号：US07151135B2

公开(公告)日：2006-12-19

申请号：US11078254

申请日：2005-03-10

申请人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

发明人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

IPC分类号： C08G63/48 ,  C08G63/91 ,  C08G69/48 ,  C08G77/00 ,  C08L89/00 ,  C08F283/00 ,  A61K47/48

CPC分类号： A61L31/16 ,  A61L24/043 ,  A61L24/08 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/041 ,  A61L2300/232 ,  A61L2300/252 ,  A61L2300/606 ,  C08B37/0075 ,  C08G65/329 ,  C08H1/00 ,  C08H1/06 ,  C08L71/02 ,  Y10S623/90 ,  Y10S623/901 ,  C08L5/16 ,  C08L71/00

摘要： Provided are crosslinked polymer compositions that include a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (—NH2) or thiol (—SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer, which contains or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further include other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents. Also disclosed are methods for using the crosslinked polymer compositions to effect adhesion between a first surface and a second surface; to effect tissue augmentation; to prevent the formation of surgical adhesions; and to coat a surface of a synthetic implant.

摘要翻译： 提供的交联聚合物组合物包括含有共价结合到含有多个亲电子基团的第二合成聚合物的多个亲核基团的第一合成聚合物。 第一合成聚合物优选是已经被修饰以含有多个亲核基团的合成多肽或聚乙二醇，例如伯氨基（-NH 2）或硫醇（-SH）基团。 第二合成聚合物可以是亲水或疏水的合成聚合物，其包含或已被衍生化为含有两个或多个亲电基团，例如琥珀酰亚胺基。 组合物还可包括其它组分，例如天然存在的多糖或蛋白质（例如糖胺聚糖或胶原）和/或生物活性剂。 还公开了使用交联聚合物组合物来实现第一表面和第二表面之间的粘合的方法; 进行组织增生; 以防止手术粘连的形成; 并涂覆合成植入物的表面。

公开(公告)号：US06534591B2

公开(公告)日：2003-03-18

申请号：US09932536

申请日：2001-08-17

申请人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

发明人： Woonza M. Rhee ,  Frank A. DeLustro ,  Richard A. Berg

IPC分类号： C08F28300

CPC分类号： A61L31/16 ,  A61L24/043 ,  A61L24/08 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/041 ,  A61L2300/232 ,  A61L2300/252 ,  A61L2300/606 ,  C08B37/0075 ,  C08G65/329 ,  C08H1/00 ,  C08H1/06 ,  C08L71/02 ,  Y10S623/90 ,  Y10S623/901 ,  C08L5/16 ,  C08L71/00

摘要： Crosslinked polymer compositions comprise a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (—NH2) or thiol (—SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer which contains, or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further comprise other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents. Also disclosed are methods for using the crosslinked polymer compositions to effect adhesion between a first surface and a second surface; to effect tissue augmentation; to prevent the formation of surgical adhesions; and to coat a surface of a synthetic implant.

公开(公告)号：US06458889B1

公开(公告)日：2002-10-01

申请号：US09883138

申请日：2001-06-15

申请人： Olof Mikael Trollsas ,  Donald G. Wallace ,  Frank A. DeLustro

发明人： Olof Mikael Trollsas ,  Donald G. Wallace ,  Frank A. DeLustro

IPC分类号： C08F28300

CPC分类号： C08H1/06 ,  A61L24/043 ,  A61L24/046 ,  A61L24/08 ,  A61L27/26 ,  A61L27/34 ,  A61L27/54 ,  A61L31/041 ,  A61L31/16 ,  A61L2300/00 ,  C08B37/0075 ,  C08F283/00 ,  C08F283/04 ,  C08F283/06 ,  C08G65/329 ,  C08G75/045 ,  C08G75/26 ,  C08G2650/50 ,  C08H1/00 ,  C08L51/003 ,  C08L53/00 ,  C08L63/00 ,  C08L71/02 ,  C08L81/02 ,  C08L2203/02 ,  C09J151/003 ,  C09J153/00 ,  C09J171/02 ,  C08L5/16 ,  C08L71/00

摘要： Crosslinkable compositions are provided that readily crosslink in situ to provide biocompatible, nonimmunogenic crosslinked biomaterials. The compositions contain at least three biocompatible, nonimmunogenic components having reactive functional groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. In a preferred embodiment, a first component is polynucleophilic, a second component is polyelectrophilic, and at least one third component contains one or more functional groups reactive with the nucleophilic moieties one the first or second component. At least one of the components is a polyfunctional hydrophilic polymer; the other components may also comprise hydrophilic polymers, or they may be low molecular weight, typically hydrophobic, crosslinkers. Methods for preparing and using the compositions are also provided. Exemplary uses include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury.

摘要翻译： 提供可交联的组合物，其易于原位交联以提供生物相容性，非免疫原性的交联生物材料。 所述组合物含有至少三种在其上具有反应性官能团的生物相容性，非免疫原性组分，其中所述官能团被选择以使组分之间进行交互反应，即交联。 在优选的实施方案中，第一组分是多亲核的，第二组分是多亲性的，并且至少一种第三组分含有一个或多个与亲核部分反应的官能团，第一组分或第二组分。 至少一种组分是多官能亲水性聚合物; 其它组分也可以包含亲水性聚合物，或它们可以是低分子量的，通常是疏水的交联剂。 还提供了制备和使用组合物的方法。 示例性用途包括组织增加，生物活性剂递送，生物粘附和预防手术或损伤后的粘连。