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1. 发明申请

WO1988001280A1 GLYCOSAMINOGLYCAN DERIVATIVES AND THEIR USE AS INHIBITORS OF TUMOR INVASIVENESS OR METASTATIC PROFUSION 审中-公开
标题翻译：谷氨酰胺糖苷衍生物及其作为肿瘤侵袭或分子生物学抑制剂的用途
公开(公告)号：WO1988001280A1
公开(公告)日：1988-02-25
申请号：PCT/US1987002035
申请日：1987-08-18
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
发明人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , NICOLSON, Garth, L. , IRIMURA, Tatsuro , NAKAJIMA, Motowo
IPC分类号： C08B37/10
CPC分类号： A61K31/715 , C08B37/0075
摘要： Method for impeding the formation of tumor metastasis or tumor invasiveness in a host. Such inhibition comprises administration to the host of a glycosaminoglycan derivative substantially devoid of anticoagulation activity and is an effective inhibitory of heparanase activity. Such a glycosaminoglycan derivative may be provided by purchase or synthesis as directed herein. Parenteral administration to a tumor-bearing host of the glycosaminoglycan derivative results in the exposure of host-borne tumor cells thereto. Such exposure to effective levels of the derivative results in the inhibition of tumor heparanase activity and a lessening of invasiveness and metastatic spread. Heparin, a glycosaminoglycan particularly effective as a heparanase inhibitor and an anti-clotting agent, is a preferred glycosaminoglycan for derivatization. Upon derivatization according to the present invention heparin may be converted into a glycosaminoglycan derivative substantially devoid of anticoagulant activity but yet being an effective inhibitor of heparanase activity. Mere reduction of heparin carboxyl groups results in the production of a glycosaminoglycan derivative inhibitory to heparanase activity but without substantially anticoagulant activity non-anticoagulating, heparanase-inhibiting glycosaminoglycan derivatives may also be prepared from heparin, for example, by: at least partial N-desulfation and then N-acetylation; or N-, O-desulfation followed by N-resulfation.
摘要翻译：阻止宿主中肿瘤转移或肿瘤浸润形成的方法。这种抑制包括向宿主施用基本上没有抗凝活性的糖胺聚糖衍生物，并且是对肝素酶活性的有效抑制。这样的糖胺聚糖衍生物可以通过如本文所述的购买或合成来提供。对葡萄糖胺聚糖衍生物的肿瘤宿主的肠胃外给药导致宿主携带的肿瘤细胞暴露于其中。这种暴露于有效水平的衍生物导致抑制肿瘤乙酰肝素酶活性和降低侵袭性和转移性扩散。肝素，作为乙酰肝素酶抑制剂和抗凝血剂特别有效的糖胺聚糖是用于衍生化的优选的糖胺聚糖。根据本发明的衍生化，肝素可以转化为基本上没有抗凝血活性但仍然是乙酰肝素酶活性的有效抑制剂的糖胺聚糖衍生物。肝素羧基的简单还原导致抑制乙酰肝素酶活性但不具有非抗凝血活性的糖胺聚糖衍生物的产生，也可由肝素制备乙酰肝素酶抑制糖胺聚糖衍生物，例如：至少部分N-脱硫然后进行N-乙酰化; 或N-，O-脱硫，随后进行N-硫酸化。

2. 发明申请

WO1992001003A1 GLYCOSAMINOGLYCAN DERIVATIVES AND THEIR USE AS INHIBITORS OF TUMOR INVASIVENESS OR METASTATIC PROFUSION-II 审中-公开
标题翻译：谷氨酸蛋白酶衍生物及其作为肿瘤免疫或分子生物学II的抑制剂
公开(公告)号：WO1992001003A1
公开(公告)日：1992-01-23
申请号：PCT/US1991004863
申请日：1991-07-10
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
发明人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , NICOLSON, Garth, L. , IRIMURA, Tatsuro , NAKAJIMA, Motowo
IPC分类号： C08B37/10
CPC分类号： A61K31/715 , A61K51/12 , A61K2123/00 , C08B37/0075 , C12N9/2402 , C12Q1/34 , C12Y302/01031 , C12Y302/01166 , G01N33/573 , G01N33/5743 , G01N33/57469 , G01N2333/924 , G01N2400/40
摘要： The present invention comprises a method for impeding the formation of tumor metastasis or tumor invasiveness in a host. Such inhibition comprises administration to the host of a glycosaminoglycan derivative substantially devoid of anticoagulation activity and is an effective inhibitory of heparanase activity. Such a glycosaminoglycan derivative may be provided by purchase or synthesis as directed herein. Parenteral administration to a tumor-bearing host of the glycosaminoglycan derivative results in the exposure of host-borne tumor cells thereto. Such exposure to effective levels of the derivative results in the inhibition of tumor heparanase activity and a lessening of invasiveness and metastatic spread. Heparin, a glycosaminoglycan particularly effective as a heparanase inhibitor and an anti-clotting agent, is a preferred glycosaminoglycan for derivatization. Upon derivatization according to the present invention heparin may be converted into a glycosaminoglycan derivative substantially devoid of anticoagulant activity but yet being an effective inhibitor of heparanase activity. Mere reduction of heparin carboxyl groups results in the production of a glycosaminoglycan derivative inhibitory to heparanase activity but without substantially anticoagulant activity non-anticoagulating, heparanase-inhibiting glycosaminoglycan derivatives may also be prepared from heparin, for example, by: at least partial N-desulfation and then N-acetylation; or N-, O-desulfation followed by N-resulfation.
摘要翻译：本发明包括阻止宿主中肿瘤转移或肿瘤浸润形成的方法。这种抑制包括向宿主施用基本上没有抗凝活性的糖胺聚糖衍生物，并且是对肝素酶活性的有效抑制。这样的糖胺聚糖衍生物可以通过如本文所述的购买或合成来提供。对葡萄糖胺聚糖衍生物的肿瘤宿主的肠胃外给药导致宿主携带的肿瘤细胞暴露于其中。这种暴露于有效水平的衍生物导致抑制肿瘤乙酰肝素酶活性和降低侵袭性和转移性扩散。肝素，作为乙酰肝素酶抑制剂和抗凝血剂特别有效的糖胺聚糖是用于衍生化的优选的糖胺聚糖。根据本发明的衍生化，肝素可以转化为基本上没有抗凝血活性但仍然是乙酰肝素酶活性的有效抑制剂的糖胺聚糖衍生物。肝素羧基的简单还原导致抑制乙酰肝素酶活性但不具有非抗凝血活性的糖胺聚糖衍生物的产生，也可由肝素制备乙酰肝素酶抑制糖胺聚糖衍生物，例如：至少部分N-脱硫然后进行N-乙酰化; 或N-，O-脱硫，随后进行N-硫酸化。

3. 发明申请

WO1991019197A1 IMMUNOCHEMICAL LOCALIZATION OF HEPARANASE IN MOUSE AND HUMAN MELANOMAS 审中-公开
标题翻译： HEPARANASE在小鼠和人类血清中的免疫化学定位
公开(公告)号：WO1991019197A1
公开(公告)日：1991-12-12
申请号：PCT/US1991003832
申请日：1991-05-30
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
发明人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , NICOLSON, Garth, L. , NAKAJIMA, Motowo , JIN, Li
IPC分类号： G01N33/573
CPC分类号： C12Y302/01166 , C07K16/3053 , C07K16/40 , C12N9/2402 , G01N33/573 , G01N33/5743
摘要： Antibodies directed against N-terminal heperanase peptide are produced. These antibodies are used for detection of heparan sulfate endoglycosidase in human and murine tumors. Localization and mounts of these heparanase antigens may ultimately be used to design appropriate therapeutic courses.
摘要翻译：产生针对N-末端heperanasease肽的抗体。这些抗体用于检测人和鼠肿瘤中的硫酸乙酰肝素糖苷内切酶。这些乙酰肝素酶抗原的定位和载体可能最终用于设计适当的治疗过程。

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