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1. 发明授权

US5997863A Attenuation of wound healing processes 失效
标题翻译：伤口愈合过程衰减
公开(公告)号：US5997863A
公开(公告)日：1999-12-07
申请号：US273109
申请日：1994-07-08
申请人： Joseph Zimmermann , Israel Vlodavsky , Clark Bennett , Pamela Danagher , Richard Broughton
发明人： Joseph Zimmermann , Israel Vlodavsky , Clark Bennett , Pamela Danagher , Richard Broughton
IPC分类号： A61K9/00 , A61K9/70 , A61K38/46 , A61K38/51 , A61L15/44 , A61P9/08 , A61P17/02 , A61P25/30 , A61P43/00 , A61K38/47 , C12N9/26 , C12N9/88
CPC分类号： A61K38/51 , Y10S530/825
摘要： Glycosaminoglycans, including heparinases 1, 2 and 3 as well as chondroitinases AC and B from the Gram negative bacteria Flavobacterium heparinum, can be used either separately or in combination to manipulate cell proliferation. In one embodiment, heparinases are administered to degrade heparan sulfate components of the extracellular matrix, thereby allowing the heparin binding growth factors which are stored in the extracellular matrix to migrate to adjacent cells. The mobility of chemoattractant agents, growth factors and cells also can be increased by treating tissues with glycosaminoglycan degrading enzymes, both chondroitinases and heparinases. The enzymatic removal of chondroitin sulfates from cell surfaces effectively increases the availability of growth factor receptors on the cell's surface. Selectively removing heparan sulfate from cell surfaces while leaving the extracellular matrix intact, conversely, inhibits cell proliferation by down regulating the cell's response to growth factors. This is achieved by targeting heparin or heparan sulfate degrading activities to the cell surface. Targeting the heparin degrading activity can be achieved by genetically engineering a ligand binding functionality into the heparinase proteins, or by physically controlling the localized enzyme concentration through the method of administration.
摘要翻译：糖胺聚糖，包括肝素酶1,2和3以及来自革兰氏阴性细菌肝炎黄杆菌的软骨素酶AC和B可以单独使用或组合使用以操纵细胞增殖。在一个实施方案中，施用肝素酶以降解细胞外基质的硫酸乙酰肝素成分，从而使存储在细胞外基质中的肝素结合生长因子迁移至相邻细胞。通过用糖胺聚糖降解酶（软骨素酶和肝素酶）处理组织，也可以增加化学引诱剂，生长因子和细胞的迁移率。从细胞表面去除硫酸软骨素有效地增加细胞表面生长因子受体的可利用性。从细胞表面选择性地去除硫酸乙酰肝素，同时使细胞外基质完好无损，相反地，通过下调细胞对生长因子的反应来抑制细胞增殖。这是通过将肝素或硫酸乙酰肝素降解活性靶向细胞表面来实现的。靶向肝素降解活性可以通过将配体结合功能遗传工程化成肝素酶蛋白质，或通过通过施用方法物理控制局部酶浓度来实现。

2. 发明授权

US07264799B2 Use of heparinases to decrease inflammatory response 失效
标题翻译：使用肝素降低炎症反应
公开(公告)号：US07264799B2
公开(公告)日：2007-09-04
申请号：US11357967
申请日：2006-02-22
申请人： D. Clark Bennett , Elizabeth Cauchon , Dominique Fink , Brigette Grouix , Ariane Hsia , Pamela Danagher , Joseph F. Zimmermann
发明人： D. Clark Bennett , Elizabeth Cauchon , Dominique Fink , Brigette Grouix , Ariane Hsia , Pamela Danagher , Joseph F. Zimmermann
IPC分类号： A61K38/51 , C12N9/88
CPC分类号： A61K38/51 , A61K47/50 , C07K2319/00 , C12N9/88 , Y10S424/81
摘要： Heparinase enzymes can be used as a medical treatment to reduce localized inflammatory responses. Treatment of activated endothelium with heparinase inhibits leukocyte rolling, adhesion and extravasation. Most of the heparin and heparan sulfate on endothelial cell surfaces and in basement membranes is degraded by exposure to heparinase. In addition, immobilized chemokines, which are attached to heparin/heparan sulfate on activated endothelium are solubilized by heparinase digestion. Heparinase can be infused into the vascular system to inhibit accumulation of leukocytes in inflamed tissue and decrease damage resulting from localized inflammations. Targeting of heparinase to activated endothelium can be accomplished through localized administration and/or use of genetically engineered heparinase containing endothelium ligand-binding domains.
摘要翻译：肝素酶可用作治疗局部炎症反应的药物治疗。用肝素酶处理激活的内皮抑制白细胞滚动，粘连和外渗。内皮细胞表面和基底膜中的大部分肝素和硫酸乙酰肝素通过暴露于肝素酶而降解。此外，通过肝素酶消化可溶解附着于活化内皮上的肝素/硫酸乙酰肝素的固定化趋化因子。肝素酶可以输注到血管系统中，以抑制发炎组织中白细胞的积累，并减少由局部炎症引起的损伤。肝素酶对活化内皮的靶向可以通过局部施用和/或使用含有内皮配体结合结构域的转基因肝素酶来实现。

3. 发明申请

US20060140928A1 Use of heparinases to decrease inflammatory response 失效
标题翻译：使用肝素降低炎症反应
公开(公告)号：US20060140928A1
公开(公告)日：2006-06-29
申请号：US11357967
申请日：2006-02-22
申请人： D. Bennett , Elizabeth Cauchon , Dominique Fink , Brigette Grouix , Ariane Hsia , Pamela Danagher , Joseph Zimmermann
发明人： D. Bennett , Elizabeth Cauchon , Dominique Fink , Brigette Grouix , Ariane Hsia , Pamela Danagher , Joseph Zimmermann
IPC分类号： A61K38/47
CPC分类号： A61K38/51 , A61K47/50 , C07K2319/00 , C12N9/88 , Y10S424/81
摘要： Heparinase enzymes can be used as a medical treatment to reduce localized inflammatory responses. Treatment of activated endothelium with heparinase inhibits leukocyte rolling, adhesion and extravasation. Most of the heparin and heparan sulfate on endothelial cell surfaces and in basement membranes is degraded by exposure to heparinase. In addition, immobilized chemokines, which are attached to heparin/heparan sulfate on activated endothelium are solubilized by heparinase digestion. Heparinase can be infused into the vascular system to inhibit accumulation of leukocytes in inflamed tissue and decrease damage resulting from localized inflammations. Targeting of heparinase to activated endothelium can be accomplished through localized administration and/or use of genetically engineered heparinase containing endothelium ligand-binding domains.
摘要翻译：肝素酶可用作治疗局部炎症反应的药物治疗。用肝素酶处理激活的内皮抑制白细胞滚动，粘连和外渗。内皮细胞表面和基底膜中的大部分肝素和硫酸乙酰肝素通过暴露于肝素酶而降解。此外，通过肝素酶消化可溶解附着于活化内皮上的肝素/硫酸乙酰肝素的固定化趋化因子。肝素酶可以输注到血管系统中，以抑制发炎组织中白细胞的积累，并减少由局部炎症引起的损伤。肝素酶对活化内皮的靶向可以通过局部施用和/或使用含有内皮配体结合结构域的转基因肝素酶来实现。

4. 发明申请

US20050191288A1 Use of heparinase to decrease inflammatory responses 审中-公开
标题翻译：使用肝素酶降低炎症反应
公开(公告)号：US20050191288A1
公开(公告)日：2005-09-01
申请号：US11118477
申请日：2005-05-02
申请人： D. Bennett , Elizabeth Cauchon , Dominique Fink , Brigette Grouix , Ariane Hsia , Pamela Danagher , Joseph Zimmermann
发明人： D. Bennett , Elizabeth Cauchon , Dominique Fink , Brigette Grouix , Ariane Hsia , Pamela Danagher , Joseph Zimmermann
IPC分类号： A61K38/00 , A61K9/14 , A61K31/00 , A61K38/46 , A61K38/47 , A61K39/395 , A61K45/00 , A61K47/48 , A61P9/10 , A61P29/00 , A61P43/00 , C12N9/24 , C12N9/88 , C12N9/96
CPC分类号： A61K38/51 , A61K47/50 , C07K2319/00 , C12N9/88 , Y10S424/81
摘要： Heparinase enzymes can be used as a medical treatment to reduce localized inflammatory responses. Treatment of activated endothelium with heparinase inhibits leukocyte rolling, adhesion and extravasation. Most of the heparin and heparan sulfate on endothelial cell surfaces and in basement membranes is degraded by exposure to heparinase. In addition, immobilized chemokines, which are attached to heparin/heparan sulfate on activated endothelium are solubilized by heparinase digestion. Heparinase can be infused into the vascular system to inhibit accumulation of leukocytes in inflamed tissue and decrease damage resulting from localized inflammations. Targeting of heparinase to activated endothelium can be accomplished through localized administration and/or use of genetically engineered heparinase containing endothelium ligand-binding domains.
摘要翻译：肝素酶可用作治疗局部炎症反应的药物治疗。用肝素酶处理激活的内皮抑制白细胞滚动，粘连和外渗。内皮细胞表面和基底膜中的大部分肝素和硫酸乙酰肝素通过暴露于肝素酶而降解。此外，通过肝素酶消化可溶解附着于活化内皮上的肝素/硫酸乙酰肝素的固定化趋化因子。肝素酶可以输注到血管系统中，以抑制发炎组织中白细胞的积累，并减少由局部炎症引起的损伤。肝素酶对活化内皮的靶向可以通过局部施用和/或使用含有内皮配体结合结构域的转基因肝素酶来实现。

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