公开(公告)号：US5766584A

公开(公告)日：1998-06-16

申请号：US458978

申请日：1995-06-02

申请人： Elazer R. Edelman ,  Aruna Nathan ,  Matthew A. Nugent

发明人： Elazer R. Edelman ,  Aruna Nathan ,  Matthew A. Nugent

IPC分类号： A61L27/00 ,  A61K35/12 ,  A61L27/50 ,  A61L31/00 ,  C12N5/071 ,  C12N11/00 ,  C12N11/08 ,  C12N5/00

CPC分类号： C12N5/069 ,  A61L27/507 ,  A61L31/005 ,  A61K35/12 ,  C12N2533/54

摘要： A composition and method are provided for inhibition of vascular smooth muscle cell proliferation following injury to the endothelial cell lining of a blood vessel such as resulting from angioplasty, vascular bypass surgery or organ transplantation. The composition is a matrix such as a biodegradable hydrogel made of a synthetic polymer, protein or polysaccharide seeded with vascular endothelial cells which can be xenografts, allografts or autografts, or genetically engineered cells. Attachment of cells to the matrix can be enhanced by coating with collagen, laminin, fibronectin, fibrin, basement membrane components or attachment peptides. Biologically active compounds such as anti-inflammatory agents may also be contained in the matrix. In the method, the matrix containing endothelial cells is implanted in a patient at a site adjacent the injury such as by wrapping the matrix around the blood vessel. The endothelial cells secrete products that diffuse into surrounding tissue but do not migrate to the endothelial cell lining of the blood vessel. The endothelial cells may be obtained by biopsy of the patient into which the matrix is implanted and the cells can be cultured in the matrix in vitro and then implanted in vivo.

摘要翻译： 提供了一种组合物和方法，用于在血管成形术，血管旁路手术或器官移植导致的血管内皮细胞内膜损伤后抑制血管平滑肌细胞增殖。 该组合物是一种基质，例如由可以是异种移植物，同种异体移植物或自体移植物或基因工程细胞的合成聚合物，蛋白质或多糖接种的血管内皮细胞制成的可生物降解的水凝胶。 可以通过用胶原，层粘连蛋白，纤连蛋白，纤维蛋白，基底膜组分或附着肽进行包被来增强细胞对基质的附着。 生物活性化合物如抗炎剂也可以包含在基质中。 在该方法中，将包含内皮细胞的基质植入患者附近的部位，例如通过将基质缠绕在血管周围。 内皮细胞分泌扩散到周围组织中的产物，但不迁移到血管的内皮细胞衬里。 内皮细胞可以通过移植基质的患者的活组织检查获得，并且细胞可以在体外在基质中培养，然后在体内植入。

公开(公告)号：US5567417A

公开(公告)日：1996-10-22

申请号：US431476

申请日：1995-05-01

申请人： Ramnath Sasisekharan ,  Marsha A. Moses ,  Matthew A. Nugent ,  Charles L. Cooney ,  Robert S. Langer

发明人： Ramnath Sasisekharan ,  Marsha A. Moses ,  Matthew A. Nugent ,  Charles L. Cooney ,  Robert S. Langer

IPC分类号： A61K47/30 ,  A61K35/74 ,  A61K38/00 ,  A61K38/46 ,  A61P9/00 ,  A61P17/00 ,  A61P27/02 ,  A61P35/00 ,  C12N9/88 ,  A61K38/51

CPC分类号： C12N9/88 ,  A61K38/00

摘要： Pharmaceutical compositions for delivering an effective dose to a desired site of a heparinase. These compositions are based on the discovery that heparinase alone can inhibit angiogenesis. The effective dosage is dependent not only on the heparinase, but also on the method and means of delivery, which can be localized or systemic. For example, in some applications, as in the treatment of psoriasis or diabetic retinopathy, the inhibitor is delivered in a topical ophthalmic carrier. In other applications, as in the treatment of solid tumors, the inhibitor is delivered by means of a biodegradable, polymeric implant.

摘要翻译： 用于将有效剂量递送至肝素酶的所需位点的药物组合物。 这些组合物基于单独的肝素酶可以抑制血管发生的发现。 有效剂量不仅取决于肝素酶，而且还取决于递送的方法和手段，其可以是局部的或全身性的。 例如，在一些应用中，如在牛皮癣或糖尿病性视网膜病变的治疗中，抑制剂在局部眼科载体中递送。 在其他应用中，如在实体瘤的治疗中，抑制剂通过可生物降解的聚合物植入物递送。

公开(公告)号：US20080227752A1

公开(公告)日：2008-09-18

申请号：US11630078

申请日：2005-06-28

申请人： Matthew A. Nugent ,  Edward Hsia ,  Jo Ann Buczek-Thomas

发明人： Matthew A. Nugent ,  Edward Hsia ,  Jo Ann Buczek-Thomas

IPC分类号： A61K31/715 ,  A61P27/02 ,  A61P11/00 ,  A61P35/04 ,  A61P9/00

CPC分类号： A61K31/727

摘要： The present invention is directed to methods for inhibition of histone acetyltransferases using glycosaminoglycans. The invention is further directed to methods for treating disorders associated with hyperacetylation by administration of glycosaminoglycans to a patient in need thereof. In one preferred embodiment, the glycosaminoglycan is a heparin or heparan sulfate oligosaccharide. Studies show that removal of sulfate residues from the O-positions of either the uronic acid or the glucosamine did not eliminate the inhibitory activity of heparan sulfate. Since a majority of heparan sulfate binding proteins appear to require O-sulfation, molecules without certain O-sulfations can be used to inhibit HATs while not interacting with most known heparin-binding proteins. In addition, specific sequences of heparin/heparan sulfate can be used to specifically inhibit various HATs.

摘要翻译： 本发明涉及使用糖胺聚糖抑制组蛋白乙酰转移酶的方法。 本发明还涉及通过向有需要的患者施用糖胺聚糖来治疗与超乙酰化相关的病症的方法。 在一个优选的实施方案中，糖胺聚糖是肝素或硫酸乙酰肝素寡糖。 研究表明，从糖醛酸或葡糖胺的O-位去除硫酸盐残留物并没有消除硫酸乙酰肝素的抑制活性。 由于大多数硫酸乙酰肝素结合蛋白似乎需要O-硫酸化，因此没有某些O-硫酸化的分子可用于抑制HAT，而不与大多数已知的肝素结合蛋白相互作用。 此外，肝素/硫酸乙酰肝素的特异性序列可用于特异性抑制各种HAT。