公开(公告)号：US5641745A

公开(公告)日：1997-06-24

申请号：US479509

申请日：1995-06-07

申请人： Zeibun Ramtoola

发明人： Zeibun Ramtoola

IPC分类号： A61K9/16 ,  A61K9/51 ,  A61K9/52 ,  A61K38/00 ,  A61K38/13 ,  A61K47/08

CPC分类号： A61K38/13 ,  A61K9/1647 ,  Y10S977/788 ,  Y10S977/795 ,  Y10S977/904 ,  Y10S977/915 ,  Y10S977/931

摘要： A controlled release pharmaceutical formulation which comprises cyclosporin entrapped in a biodegradable polymer to form microspheres or nanospheres such that the cyclosporin is substantially in an amorphous state and the biodegradable polymer comprises greater than 12.5% w/w poly(lactide). The biodegradable polymer is suitably poly-D,L-lactide or a blend of poly-D,L-lactide and poly-D,L-lactide-co-glycolide. Additionally, an enteric coating can be applied to the microspheres or nanospheres or to the oral dosage form incorporating the microspheres or nanospheres to protect the formulation while it passes through the stomach. A particularly suitable formulation comprises 50% w/w cyclosporin-loaded 80:20 blend of poly-D,L-lactide-co-glycolide to poly-D,L-lactide micro- and/or nanospheres. This formulation has the combined properties of nearly complete but relatively slow release of cyclosporin within 8 hours and is useful for targeting cyclosporin to the small intestine when administered orally.

摘要翻译： 一种控释药物制剂，其包含环包埋在可生物降解聚合物中以形成微球体或纳米球体的环孢菌素，使得环孢菌素基本上处于无定形状态，生物可降解聚合物包含大于12.5％w / w的聚（丙交酯）。 生物可降解聚合物适宜为聚-D，L-丙交酯或聚-D，L-丙交酯和聚-D，L-丙交酯 - 共 - 乙交酯的共混物。 此外，肠溶衣可以应用于微球体或纳米球体或结合微球体或纳米球体的口服剂型，以在制剂通过胃部时保护制剂。 一种特别合适的制剂包含50％w / w的环孢菌素负载的聚-D，L-丙交酯 - 共 - 乙交酯的80:20共混物与聚-D，L-丙交酯微米和/或纳米球。 该制剂具有在8小时内几乎完全但相对缓慢释放环孢菌素的组合性质，并且用于口服给药时将环孢菌素靶向小肠。

公开(公告)号：US5641515A

公开(公告)日：1997-06-24

申请号：US474161

申请日：1995-06-07

申请人： Zeibun Ramtoola

发明人： Zeibun Ramtoola

IPC分类号： A61K9/51 ,  A61K38/28 ,  A61K47/48 ,  A61K9/14

CPC分类号： A61K9/5138 ,  A61K38/28 ,  A61K47/48176 ,  A61K47/489 ,  A61K9/5161 ,  B82Y5/00 ,  Y10S977/775 ,  Y10S977/915 ,  Y10T428/2982 ,  Y10T428/2984 ,  Y10T428/2985 ,  Y10T428/2989 ,  Y10T428/2991

摘要： A controlled release pharmaceutical formulation comprises nanoparticles formed of a biodegradable polycyanoacrylate polymer in which insulin is entrapped, the insulin being complexed to the polycyanoacrylate. These particles are capable of releasing bioactive insulin in vivo at a slower release rate than nanoparticles in which the insulin is free. The formulation may comprise a mixture of nanoparticles in which the insulin is free and nanoparticles in which it is complexed, so as to obtain the desired release profile. The nanoparticles have a preferred loading of 15-25% w/v insulin and a preferred size of 100-400 nm. Administration may be oral or parenteral, and for oral administration, an enteric coating may be provided to target release to the small intestine. Complexing of the insulin is achieved by the polymerisation of cyanoacrylate monomer in the presence of insulin at a low pH, preferably at about pH=2.

摘要翻译： 控释药物制剂包含由生物可降解的聚氰基丙烯酸酯聚合物形成的纳米颗粒，其中胰岛素被截留，胰岛素与聚氰基丙烯酸酯络合。 这些颗粒能够以比其中胰岛素游离的纳米颗粒更慢的释放速率在体内释放生物活性胰岛素。 制剂可以包含其中胰岛素是游离的纳米颗粒和其中复合的纳米颗粒的混合物，以便获得所需的释放曲线。 纳米颗粒具有15-25％w / v胰岛素的优选负载量和100-400nm的优选尺寸。 给药可以是口服或胃肠外给药，并且对于口服给药，可以提供肠溶衣以靶向释放到小肠。 胰岛素的络合通过在低pH，优选约pH = 2的胰岛素存在下聚合氰基丙烯酸酯单体来实现。