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    Liver-receptor imaging injection, dispensing method and pharmaceutical composition thereof
    1.
    发明授权
    Liver-receptor imaging injection, dispensing method and pharmaceutical composition thereof 有权
    肝 - 受体成像注射，分配方法及其药物组合物

    公开(公告)号：US09040017B2

    公开(公告)日：2015-05-26

    申请号：US13243225

    申请日：2011-09-23

    申请人： Mei-Hui Wang ,  Wuu-Jyh Lin ,  Hung-Man Yu ,  Chuan-Yi Chien ,  Ping-Yen Wang

    发明人： Mei-Hui Wang ,  Wuu-Jyh Lin ,  Hung-Man Yu ,  Chuan-Yi Chien ,  Ping-Yen Wang

    IPC分类号： A61K51/04 ,  A61K51/06

    CPC分类号： A61K51/0491 ,  A61K51/0406 ,  A61K51/0497 ,  A61K51/065

    摘要： The present invention is related to a pharmaceutical composition for a liver-receptor imaging injection, the pharmaceutical composition including a bi-functional compound which has a ASGPR specificity, wherein the bi-functional compound includes a backbone of alpha-amino acid (or the derivatives thereof) and a poly-galactosamine chain (or a poly-lactose chain) connected to the alpha-amino acid. Thereby, the pharmaceutical composition can quantify potential of liver storage ability and evaluate severity of the course of liver disease. A liver-receptor imaging injection using the same and the one-step dispensing method thereof are also provided to improve defects of iodine-labeled and overcome disadvantages of the reduced labeling-yield and the instability after autoclave sterilization.

    摘要翻译： 本发明涉及一种肝 - 受体成像注射用药物组合物，该药物组合物包含具有ASGPR特异性的双功能化合物，其中双官能化合物包括α-氨基酸（或其衍生物 ）和与α-氨基酸连接的聚半乳糖胺链（或聚乳糖链）。 因此，药物组合物可以量化肝脏储存能力的潜力并评估肝脏疾病过程的严重程度。 还提供使用其的肝受体成像注射器及其一步式分配方法，以改善碘标记的缺陷，克服降压标记产率和高压灭菌后的不稳定性的缺点。

    LIVER- RECEPTOR IMAGING INJECTION, DISPENSING METHOD AND PHARMACEUTICAL COMPOSITION THEREOF
    2.
    发明申请
    LIVER- RECEPTOR IMAGING INJECTION, DISPENSING METHOD AND PHARMACEUTICAL COMPOSITION THEREOF 有权
    肝脏摄取成像注射，分配方法及其药物组合物

    公开(公告)号：US20120107236A1

    公开(公告)日：2012-05-03

    申请号：US13243225

    申请日：2011-09-23

    申请人： MEI-HUI WANG ,  Wuu-Jyh Lin ,  Hung-Man Yu ,  Chuan-Yi Chien ,  Ping-Yen Wang

    发明人： MEI-HUI WANG ,  Wuu-Jyh Lin ,  Hung-Man Yu ,  Chuan-Yi Chien ,  Ping-Yen Wang

    IPC分类号： A61K103/20 ,  C07F5/00 ,  A61P43/00

    CPC分类号： A61K51/0491 ,  A61K51/0406 ,  A61K51/0497 ,  A61K51/065

    摘要： The present invention is related to a pharmaceutical composition for a liver-receptor imaging injection, the pharmaceutical composition including a bi-functional compound which has a ASGPR specificity, wherein the bi-functional compound includes a backbone of alpha-amino acid (or the derivatives thereof) and a poly-galactosamine chain (or a poly-lactose chain) connected to the alpha-amino acid. Thereby, the pharmaceutical composition can quantify potential of liver storage ability and evaluate severity of the course of liver disease. A liver-receptor imaging injection using the same and the one-step dispensing method thereof are also provided to improve defects of iodine-labeled and overcome disadvantages of the reduced labeling-yield and the instability after autoclave sterilization.

    摘要翻译： 本发明涉及一种肝 - 受体成像注射用药物组合物，该药物组合物包含具有ASGPR特异性的双功能化合物，其中双官能化合物包括α-氨基酸（或其衍生物 ）和与α-氨基酸连接的聚半乳糖胺链（或聚乳糖链）。 因此，药物组合物可以量化肝脏储存能力的潜力并评估肝脏疾病过程的严重程度。 还提供使用其的肝受体成像注射器及其一步式分配方法，以改善碘标记的缺陷，克服降压标记产率和高压灭菌后的不稳定性的缺点。

    RADIOLABELING METHOD USING MULTIVALENT GLYCOLIGANDS AS HEPATIC RECEPTOR IMAGING AGENT
    5.
    发明申请
    RADIOLABELING METHOD USING MULTIVALENT GLYCOLIGANDS AS HEPATIC RECEPTOR IMAGING AGENT 审中-公开
    使用多种甘氨酸作为胃肠吸收成像剂的放射性标记方法

    公开(公告)号：US20110097264A1

    公开(公告)日：2011-04-28

    申请号：US12779328

    申请日：2010-05-13

    申请人： Mei-Hui Wang ,  Wuu-Jyh Lin ,  Chuan-Yi Chien ,  Hung-Man Yu ,  Reiko Takasaka Lee ,  Yuan-Chuan Lee

    发明人： Mei-Hui Wang ,  Wuu-Jyh Lin ,  Chuan-Yi Chien ,  Hung-Man Yu ,  Reiko Takasaka Lee ,  Yuan-Chuan Lee

    IPC分类号： A61K51/08 ,  C07K5/083 ,  C07F5/00 ,  A61K51/04

    CPC分类号： A61K51/0491 ,  A61K51/0497 ,  C07F13/005 ,  C07K1/13

    摘要： A radiolabeling method using a multivalent glycoligand as hepatic receptor imaging agent is provided. The multivalent glycoligand-DTPA derivatives (In-111-DTPA-hexa lactoside and In-111-DTPA-tri-galactosamine glycoside) labeled with In-111 are used as hepatic receptor imaging agent. The effects of imaging of a hepatic receptor in different species are evaluated, the lowest specific radioactivity values of hepatic receptor imaging required in different species are discovered. Since the specificity of the human ASGPR closely resembles that of the mouse. This kind of radiolabelling method, agent and related study about specific radioactivity could be used in clinical trial in the future.

    摘要翻译： 提供了一种使用多价糖配位体作为肝脏受体成像剂的放射性标记方法。 用In-111标记的多价甘油配体-DTPA衍生物（In-111-DTPA-hexa lactoside和In-111-DTPA-tri-galactosamine glycoside）用作肝脏受体显像剂。 对不同物种肝受体成像的影响进行了评估，发现了不同物种所需肝脏受体成像的最低比放射性值。 由于人类ASGPR的特异性与小鼠的特异性非常相似。 这种放射性标记方法，药剂和相关研究有关的放射性可以在今后的临床试验中使用。

    Liver-targeting agents and their synthesis
    6.
    发明授权
    Liver-targeting agents and their synthesis 有权
    肝靶向剂及其合成

    公开(公告)号：US08552163B2

    公开(公告)日：2013-10-08

    申请号：US12891004

    申请日：2010-09-27

    申请人： Reiko Takasaka Lee ,  Yuan-Chuan Lee ,  Mei-Hui Wang ,  Wuu-Jyh Lin

    发明人： Reiko Takasaka Lee ,  Yuan-Chuan Lee ,  Mei-Hui Wang ,  Wuu-Jyh Lin

    IPC分类号： C07H17/02 ,  C07C229/00

    CPC分类号： C07H15/04

    摘要： This invention provides novel liver targeting agents and their synthetic methods. A liver targeting agent, with a lysine based nitrilotriacetic acid structure as backbone which acquires multivalency with saccharide groups, to bind with a galactosamine chain or lactose chain is disclosed. In particular, only one amino acid L-lysine is involved to provide trivalency. All carboxyl groups in Nε-benzyloxycarbonyl-Nα-dicarboxymethyl-L-lysine can be conjugated with three glycosides of ahGalNAc or ahLac in one step. This invention also provides a hexa-lactoside. In particular, the TFA-AHA-Asp was used to conjugate 2 molecules of NTA(ahLac)3. This invention also provides a method for adding a spacer between NTA and DTPA. The extended hepatocyte-specific glyco-ligand has higher 111In-radiolabelling yield than those non-extended.

    摘要翻译： 本发明提供新型肝靶向剂及其合成方法。 公开了以赖氨酸的次氮基三乙酸结构作为骨架的肝靶向剂，其以糖基取代多价，与半乳糖胺链或乳糖链结合。 特别地，仅涉及一个氨基酸L-赖氨酸以提供三价值。 Nepsilon-苄氧基羰基-Nalpha-二羧甲基-L-赖氨酸中的所有羧基可以在一个步骤中与ahGalNAc或ahLac的三种糖苷缀合。 本发明还提供了六乳糖苷。 特别地，TFA-AHA-Asp用于结合2分子的NTA（ahLac）3。 本发明还提供了一种在NTA和DTPA之间添加间隔物的方法。 延长的肝细胞特异性糖配体比未延长的肝细胞特异性糖配体具有更高的111In-放射性标记产率。

    Method for preparing precursor used for labeling hepatocyte receptor and containing trisaccharide and DTPA ligand
    8.
    发明授权
    Method for preparing precursor used for labeling hepatocyte receptor and containing trisaccharide and DTPA ligand 有权
    制备用于标记肝细胞受体并含有三糖和DTPA配体的前体的方法

    公开(公告)号：US09045513B2

    公开(公告)日：2015-06-02

    申请号：US13571731

    申请日：2012-08-10

    申请人： Chih-Yuan Lin ,  Yu Chang ,  Jen-Tsung Wang ,  Cheng-Fang Hsu ,  Wei-Ti Kuo ,  Hung-Wen Yu ,  Wuu-Jyh Lin ,  Mei-Hui Wang

    发明人： Chih-Yuan Lin ,  Yu Chang ,  Jen-Tsung Wang ,  Cheng-Fang Hsu ,  Wei-Ti Kuo ,  Hung-Wen Yu ,  Wuu-Jyh Lin ,  Mei-Hui Wang

    IPC分类号： C07H15/04 ,  C07H1/06 ,  C07K1/13

    CPC分类号： C07H1/06 ,  C07H15/04 ,  C07K1/13

    摘要： A method for preparing a precursor used to label hepatocyte receptors is revealed. The precursor contains a bifunctional structure including trisaccharide and DTPA ligand. During synthesis processes of the precursor, silica gel columns and Reverse phase-18 (RP-18) columns are used for purification. Thus both the purification times and cost of each purification are reduced. Moreover, use diethyl ether to facilitate precipitation of products and remove a part of coupling reagent. Removing the coupling reagent helps purification of products. Furthermore, Nα,Nα-bis(carboxymethyl)-L-lysine hydrate and benzyl chloroformate are coupled to form a trisaccharide skeleton so as to ensure the yield rate of trisaccharide structure.

    摘要翻译： 揭示了制备用于标记肝细胞受体的前体的方法。 该前体含有包括三糖和DTPA配体的双功能结构。 在前体的合成过程中，使用硅胶柱和反相18（RP-18）柱进行纯化。 因此，每次纯化的纯化时间和成本均降低。 此外，使用乙醚促进产物沉淀并除去一部分偶联剂。 去除偶联剂有助于净化产品。 此外，Nα，Nα-双（羧甲基）-L-赖氨酸水合物和氯甲酸苄酯偶联形成三糖骨架，以确保三糖结构的产率。

    Preparation method of radiation sensitive copolymer carrier for coating radiated nanoparticles and chemotherapy drugs
    10.
    发明申请
    Preparation method of radiation sensitive copolymer carrier for coating radiated nanoparticles and chemotherapy drugs 有权
    辐射敏感性纳米粒子和化疗药物辐射敏感性共聚物载体的制备方法

    公开(公告)号：US20160113884A1

    公开(公告)日：2016-04-28

    申请号：US14522583

    申请日：2014-10-24

    申请人： Wuu-Jyh Lin ,  Ting-Shien Duh ,  Wei-Ming Li ,  Ming-Hsin Li

    发明人： Wuu-Jyh Lin ,  Ting-Shien Duh ,  Wei-Ming Li ,  Ming-Hsin Li

    IPC分类号： A61K9/51 ,  A61K31/704

    CPC分类号： A61K9/5146 ,  A61K9/5192 ,  A61K31/704

    摘要： The preparation method of radiation-sensitive copolymer carrier for coating radiated nanoparticles and/or chemotherapy drugs includes forming a nanosphere by diselenide block copolymers and DSPE-PEG-biomarkers to coat chemotherapy drugs and/or radiated nanoparticles that can be released from the opened nanosphere by protons penetrating tissue during proton therapy. The treatment effect of proton therapy is enhanced by two ways of using the radiated nanoparticles released from an opened nanosphere to produce nuclear fission with the protons for releasing electrons to destroy cancer cells of tumor and the chemotherapy drugs released from the opened nanosphere for distributing among tissue to kill the cancer cells of the tumor.

    摘要翻译： 用于涂覆辐射纳米颗粒和/或化疗药物的辐射敏感性共聚物载体的制备方法包括通过二硒化物嵌段共聚物和DSPE-PEG-生物标志物形成纳米球，以涂覆可以从开放的纳米球释放的化学药物和/或辐射纳米颗粒， 在质子治疗期间质子穿透组织。 质子治疗的治疗效果通过使用从开放的纳米球释放的辐射纳米颗粒产生核裂变以释放电子以释放肿瘤的肿瘤细胞的质子和从打开的纳米球释放的化疗药物在组织间分布的两种方式得到增强 杀死肿瘤的癌细胞。