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1. 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。

2. 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。

3. 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。

4. 发明申请

US20130225681A1 Phenylketone Carboxylate Compounds and Pharmaceutical Uses Thereof 有权
标题翻译：苯甲酮羧酸酯化合物及其药物用途
公开(公告)号：US20130225681A1
公开(公告)日：2013-08-29
申请号：US13882363
申请日：2011-10-26
申请人： Boulos Zacharie , Christopher Penney , Shaun Abbott , Lyne Gagnon , Brigette Grouix , Pierre Laurin
发明人： Boulos Zacharie , Christopher Penney , Shaun Abbott , Lyne Gagnon , Brigette Grouix , Pierre Laurin
IPC分类号： C07C59/90 , C07C229/18 , C07C59/84 , C07C69/92 , C07C59/68 , C07C62/38 , C07C323/52
CPC分类号： C07C59/90 , A61K31/192 , A61K31/196 , A61K31/222 , A61K31/235 , C07C59/68 , C07C59/84 , C07C62/38 , C07C65/32 , C07C69/92 , C07C217/84 , C07C225/22 , C07C229/18 , C07C323/20 , C07C323/52 , C07C323/62 , C07C2602/08
摘要： Phenylketone carboxylate compounds of Formula I, wherein n=2-6; R═C(0); —OC(O)— or —CH(OH)—; A is (CH2)mCOOH, W(CH2)mCOOH or YCH(COOH)((CH2)pCH3) when B is Ft B is (CH2)mCOOH, W(CH2)mCOOH or YCH(COOH)((CH2)pCH3) when A is Ft or A and B form a 5-7 membered cycloalkyl substituted with COOFt W=0, S or NFt Y=0,S,NH or CH2; m=0-2; p=1-7; have been prepared. These compounds and their pharmaceutically acceptable salts have beneficial therapeutic effects to prevent or treat a condition related to (l) blood disorders, (ii) inflammation related diseases, (iii) renal disorders and/or renal disorders complications, or (iv) fibrosis-related organ dysfunction.
摘要翻译：式I的苯甲酮羧酸酯化合物，其中n = 2-6; R = C（0）; -OC（O） - 或-CH（OH） - ; 当B是Ft B是（CH2）mCOOH，W（CH2）mCOOH或YCH（COOH）（（CH2）pCH3）时，A是（CH2）mCOOH，W（CH2）mCOOH或YCH 当A为Ft或A和B形成被COOFt W = 0取代的5-7元环烷基时，S或NFt Y = 0，S，NH或CH 2; m = 0-2; p = 1-7; 已经准备好了这些化合物及其药学上可接受的盐具有有益的治疗效果，以预防或治疗与（l）血液病症有关的病症，（ii）炎症相关疾病，（iii）肾脏疾病和/或肾脏疾病并发症，或（iv）纤维化 - 相关器官功能障碍。

5. 发明申请

US20130225683A1 Compounds and Pharmaceutical Compositions for Uses in Diabetes 审中-公开
标题翻译：用于糖尿病的化合物和药物组合物
公开(公告)号：US20130225683A1
公开(公告)日：2013-08-29
申请号：US13882373
申请日：2011-10-26
申请人： Lyne Gagnon , Brigette Grouix , Pierre Laurin
发明人： Lyne Gagnon , Brigette Grouix , Pierre Laurin
IPC分类号： A61K31/192 , A61K31/155 , A61K31/426 , A61K31/20
CPC分类号： A61K31/192 , A61K31/155 , A61K31/20 , A61K31/426
摘要： New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I, IA, IB and IC, and their pharmaceutical acceptable salts are described for prevention or treatment of diabetes or a diabetes-related disorder in a subject in need thereof. Diabetes and diabetes-related disorder include Type I diabetes, Type II diabetes, maturity-onset diabetes of the young, latent autoimmune diabetes of adults (LADA), gestational diabetes, diabetic nephropathy, proteinuria, ketonuria, obesity, hyperglycemia, glucose intolerance, insulin resistance, hyperinsulinemia, hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglyceridemia, dyslipidemia, metabolic syndrome, syndrome X, diabetic neuropathy, diabetic retinopathy, hypoglycemia, cardiovascular disease, atherosclerosis, diabetic kidney disease, ketoacidosis, thrombotic disorders, sexual dysfunction, dermatopathy, edema, metabolic syndrome and renal disorders. The related pharmaceutical compositions and methods are also described. These compounds can be used in combination with comprising a therapeutic agent for lowering or controlling blood glucose level such as metformin or a thiazolidinedione.
摘要翻译：描述了用于预防或治疗有需要的受试者中的糖尿病或糖尿病相关疾病的式I，式I，IA，IB和IC的苯甲酮羧酸酯化合物和取代的芳族化合物及其药学上可接受的盐的新用途。糖尿病和糖尿病相关疾病包括I型糖尿病，II型糖尿病，年轻成熟期糖尿病，成人潜伏性自身免疫性糖尿病（LADA），妊娠糖尿病，糖尿病肾病，蛋白尿，酮尿症，肥胖症，高血糖症，葡萄糖不耐症，胰岛素高血脂，高脂血症，高脂血症，高甘油三酯血症，血脂异常，代谢综合征，综合征X，糖尿病性神经病，糖尿病性视网膜病变，低血糖症，心血管病，代谢综合征和肾脏疾病。还描述了相关的药物组合物和方法。这些化合物可以与降低或控制血糖水平的治疗剂如二甲双胍或噻唑烷二酮组合使用。

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