公开(公告)号：US20100119590A1

公开(公告)日：2010-05-13

申请号：US12501606

申请日：2009-07-13

申请人： Ning Hu ,  Gerard M. Jensen ,  Michele Sulivan ,  Stephanie Yang

发明人： Ning Hu ,  Gerard M. Jensen ,  Michele Sulivan ,  Stephanie Yang

IPC分类号： A61K9/127 ,  A61K31/55 ,  A61P35/00

CPC分类号： A61K9/127 ,  A61K9/1277 ,  A61K9/1278 ,  A61K31/137 ,  A61K31/55 ,  A61K31/704

摘要： A method for encapsulation of pharmaceutical agents (e.g., antineoplastic agents) in liposomes is provided, having preferably a high drug:lipid ratio. Liposomes can be made by a process that loads the drug by an active mechanism using a transmembrane pH gradient. Using this technique, trapping efficiencies approach 100%. Drug:lipid ratios employed are higher than for older traditional liposome preparations, and the release rate of the drug from the liposomes is reduced. After loading, residual acid is quenched with a quenching agent that is base permeable at low temperatures. The residual aciditiy is thus reduced and chemical stability (e.g. against hydrolysis) is enhanced. The stability of both the liposome and the pharmaceutical agent is thus maintained, prior to administration. The pH gradient is, however, present when the liposome is administered in vivo because the quenching agent rapidly exits the liposome.

摘要翻译： 提供了在脂质体中封装药物（例如抗肿瘤剂）的方法，其优选具有高的药物：脂质比。 可以通过使用跨膜pH梯度的活性机制加载药物的方法制备脂质体。 使用这种技术，捕获效率接近100％。 药物：使用的脂质比例高于较老的传统脂质体制剂，并且药物从脂质体的释放速率降低。 加载后，残留的酸用低温基本可渗透的淬火剂骤冷。 残留的酸性因此降低，并且化学稳定性（例如抗水解）得到增强。 因此在施用之前维持脂质体和药剂的稳定性。 然而，当脂质体在体内施用时，pH梯度存在，因为猝灭剂快速离开脂质体。