申请人:D-Pharm, Ltd.
公开号:US06774121B1
公开(公告)日:2004-08-10
The invention discloses prodrugs comprising anti-proliferative drugs covalently linked, via bridging group, to a phospholipid moiety such that the active species is preferentially released, preferably by enzymatic cleavage, at the required site of action. The invention further discloses pharmaceutical compositions said prodrugs and the uses thereof for the treatment of diseases and disorders related to inflammatory, to degenerative or atrophic conditions, and to uncontrolled cell growth. FIG. 1 depicts a graph of animal survival during the course of an experiment wherein mice were i.p. transplanted with 11210 mouse leukemia cells and then treated with vehicle only (squares), MTX (triangles) or molar equivalent dose of DP-MTX071 (circles) according to the regiment described example in Example 11.
该发明揭示了包含抗增殖药物的前药,通过桥联基与磷脂基团共价连接,使活性物种优先释放,最好通过酶解裂解,在所需的作用部位释放。该发明进一步揭示了含有这些前药的药物组合物及其用途,用于治疗与炎症、变性或萎缩症状以及不受控制的细胞增殖相关的疾病和紊乱。图1描述了在实验过程中动物存活率的图表,其中小鼠被i.p.移植了11210只鼠白血病细胞,然后根据第11例中描述的方案用仅载体(方块)、MTX(三角形)或DP-MTX071的等摩尔剂量(圆圈)进行治疗。