公开(公告)号：US20120244193A1

公开(公告)日：2012-09-27

申请号：US13381483

申请日：2010-05-19

申请人： Xiaohai Tang ,  Yu Qiu ,  Xin Song

发明人： Xiaohai Tang ,  Yu Qiu ,  Xin Song

IPC分类号： A61K9/00 ,  A61P35/00 ,  A61K31/704

CPC分类号： A61K31/704 ,  A61K47/61 ,  A61K47/6939

摘要： The invention relates to a passive solid tumor-targeted anticancer prodrug and a preparation method thereof, belonging to the field of antitumor drugs. The preparation method includes the following steps: reacting low molecular weight pectin with Mw of 5,000-45,000 with doxorubicin to obtain a pectin-doxorubicin conjugate with Mw of 100,000-1,000,000, preparing the conjugate into a suspension, and treating the suspension in an ultra-high pressure nano homogenizer to obtain the passive solid tumor-targeted anticancer prodrug with particle size of 100 nm-200 nm and melting point of 220-245°, wherein the pectin and doxorubicin are linked by an amide bond, and the pectin is linked by an ester bond formed by condensing carboxyl groups and hydroxyl groups of pectin molecules. Cell inhibition rate of the anticancer prodrug for humanized lung cancer cells NCI-H446 and A549 is equivalent to that of doxorubicin hydrochloride. In the efficacy research of melanoma B16 pulmonary metastasis model mice, the life span of tumor-bearing mice is 42.3±12.4 days, which is remarkably higher than that of the doxorubicin hydrochloride group (23.1±10.2 days).

摘要翻译： 本发明涉及一种属于抗肿瘤药物领域的被动实体肿瘤靶向抗癌药物及其制备方法。 该制备方法包括以下步骤：使用多柔比星使低分子量果胶与5,000〜45,000的Mw反应，得到Mw为100,000-1,000,000的果胶 - 多柔比星缀合物，将该缀合物制备成悬浮液， 高压纳米均化器，得到粒径为100nm-200nm，熔点为220-245°的被动实体肿瘤靶向抗癌前药，其中果胶和多柔比星通过酰胺键连接，果胶通过 通过缩合果胶分子的羧基和羟基形成的酯键。 人源化肺癌细胞NCI-H446和A549的抗癌前药的细胞抑制率与盐酸多柔比星的细胞抑制率相当。 在黑色素瘤B16肺转移模型小鼠的功效研究中，荷瘤小鼠的寿命为42.3±12.4天，明显高于盐酸多柔比星组（23.1±10.2天）。

公开(公告)号：US20130172283A1

公开(公告)日：2013-07-04

申请号：US13695048

申请日：2011-04-22

申请人： Xiaohai Tang ,  Yu Qiu

发明人： Xiaohai Tang ,  Yu Qiu

IPC分类号： A61K31/704

CPC分类号： A61K31/704 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/32 ,  A61K47/61

摘要： The invention belongs to the pharmaceutical field, and particularly relates to a lyophilized formulation of pectin-adriamycin conjugate and a preparation method thereof. In order to solve insolubility problem of the pectin-adriamycin conjugate (hereinafter referred to as PAC), improve bioavailability and facilitate preparation, the inventor prepared the PAC into a nanosuspension. However, as long-term stability of the nanosuspension is poor, the inventor proposed to prepare the nanosuspension into a lyophilized formulation, that is, an insoluble pectin-adriamycin conjugate is prepared into a suspension or nanosuspension, and a lyophilized support agent is added to the suspension for lyophilization treatment to prepare the lyophilized formulation. Lyophilized products prepared from the nanosuspension are characterized by enhanced stability of nano-particle size and enhanced stability of drug loading rate, which provides a new solution for clinical application of the PAC.

摘要翻译： 本发明属于制药领域，特别涉及果胶 - 阿霉素缀合物的冻干制剂及其制备方法。 为了解决果胶 - 阿霉素缀合物（以下简称PAC）的不溶性问题，提高生物利用度和促进制剂，本发明人将PAC制备成纳米悬浮液。 然而，由于纳米悬浮液的长期稳定性差，本发明人提出将纳米悬浮液制备成冻干制剂，即将不溶性果胶 - 阿霉素缀合物制备成悬浮液或纳米悬浮液，并将冻干的载体添加到 用于冻干处理以制备冻干制剂的悬浮液。 从纳米悬浮液制备的冻干产品的特征在于增强了纳米粒径的稳定性和药物加载速率的稳定性，为临床应用PAC提供了新的解决方案。