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    Drug-containing nanoparticle, process for producing the same and parenterally administered preparation from the nanoparticle
    3.
    发明申请
    Drug-containing nanoparticle, process for producing the same and parenterally administered preparation from the nanoparticle 审中-公开
    含药纳米颗粒，其制备方法和从该纳米颗粒肠胃外给药的制剂

    公开(公告)号：US20070077286A1

    公开(公告)日：2007-04-05

    申请号：US10596828

    申请日：2004-10-12

    申请人： Tsutomu Ishihara ,  Yutaka Mizushima ,  Jun Suzuki ,  Junzou Sekine ,  Yoko Yamaguchi ,  Rie Igarashi

    发明人： Tsutomu Ishihara ,  Yutaka Mizushima ,  Jun Suzuki ,  Junzou Sekine ,  Yoko Yamaguchi ,  Rie Igarashi

    IPC分类号： A61K9/70 ,  A61K9/14

    CPC分类号： A61K9/0024 ,  A61K9/5123 ,  A61K9/5146 ,  A61K9/5192 ,  A61K31/07 ,  A61K31/122 ,  A61K31/198

    摘要： To provide an external preparation or injectable preparation that exerts the effect of enabling transdermal or transmucosal in viva absorption of fat-soluble drugs and water-soluble drugs not having been satisfactorily attained hitherto and that contains a highly absorbable fat-soluble/water-soluble drug, the injectable preparation especially aiming at sustained-release and target effects. In particular, drug-containing nanoparticles (secondary nanoparticles) are provided by causing primary nanoparticles containing a fat-soluble drug or fat-solubilized water-soluble drug to act with a bivalent or trivalent metal salt. Further, drug-containing nanoparticles (tertiary nanoparticles) are provided by first causing primary nanoparticles containing a fat-soluble drug or fat-solubilized water-soluble drug to act with a bivalent or trivalent metal salt to thereby obtain secondary nanoparticles and thereafter causing a monovalent to trivalent basic salt to act on the secondary nanoparticles. Still further, there are provided a process for producing these nanoparticles, and a transdermal or transmucosal external preparation or injectable preparation in which these nanoparticles are contained.

    摘要翻译： 提供一种外用制剂或注射制剂，其具有使透皮或透粘膜能够吸收迄今为止未达到令人满意的脂溶性药物和水溶性药物的含量，并且含有高吸收性脂溶性/水溶性药物 ，注射剂，特别是针对持续释放和目标效应。 特别地，通过使含有脂溶性药物或脂溶性水溶性药物的一次纳米粒子与二价或三价金属盐起作用来提供含药纳米粒子（二次纳米粒子）。 此外，通过首先使含有脂溶性药物或脂溶性水溶性药物的一次纳米颗粒与二价或三价金属盐起作用，从而获得二次纳米粒子，然后使单价 至三价碱性盐作用于二次纳米颗粒。 此外，提供了制备这些纳米颗粒的方法，以及包含这些纳米颗粒的透皮或透粘膜外用制剂或可注射制剂。

    Method of controlling paticle size of retinoic acid nanoparticles coated with polyvalent metal inorganic salt and nanoparticles obtained by the controlling method
    5.
    发明申请
    Method of controlling paticle size of retinoic acid nanoparticles coated with polyvalent metal inorganic salt and nanoparticles obtained by the controlling method 审中-公开
    通过控制方法获得的用多价金属无机盐和纳米粒子涂覆的视黄酸纳米颗粒的粒度控制方法

    公开(公告)号：US20070014863A1

    公开(公告)日：2007-01-18

    申请号：US10595412

    申请日：2003-10-15

    申请人： Yoko Yamaguchi ,  Rie Igarashi ,  Yutaka Mizushima ,  Mitsuko Takenaga

    发明人： Yoko Yamaguchi ,  Rie Igarashi ,  Yutaka Mizushima ,  Mitsuko Takenaga

    IPC分类号： A61K9/14 ,  A61K31/203

    CPC分类号： A61K9/5115 ,  A61K9/1075 ,  A61K9/5089 ,  A61K9/5192 ,  A61K31/203 ,  A61K47/02

    摘要： Nanoparticles containing retinoic acid have reduced irritancy of retinoic acid and are suitable for subcutaneous or intravenous administration, as well as for use in sustained-release preparation. The high skin permeability of the nanoparticles makes them suitable for use in pharmaceutical or non-pharmaceutical external preparations or cosmetics intended for skin application. The present invention provides a method for adjusting the particle size of such nanoparticles and nanoparticles produced by such a method. Specifically, the method involves dispersing retinoic acid dissolved in a lower alcohol in an aqueous alkali solution; adding a nonionic surfactant to the dispersion to form a mixed micelle; adding to the micelle a halide or acetate of divalent metal along with a carbonate or phosphate of alkali metal so that the molar ratio of the former to the latter is 1:0 to 1:1.0, thereby depositing a coating of inorganic salt of polyvalent metal on the surface of the micelle; and adjusting the average particle size of the resulting nanoparticles to 5 to 300 nm. The inorganic salt of polyvalent metal may be calcium carbonate, zinc carbonate, or calcium phosphate.

    摘要翻译： 含视黄酸的纳米粒子具有降低视黄酸的刺激性，适用于皮下或静脉内给药以及用于持续释放制剂。 纳米颗粒的高皮肤渗透性使得它们适用于用于皮肤应用的药物或非药物外用制剂或化妆品。 本发明提供了一种调节由这种方法生产的纳米颗粒和纳米粒子的粒径的方法。 具体地说，该方法包括将溶解在低级醇中的视黄酸分散在碱性水溶液中; 向分散体中加入非离子表面活性剂以形成混合胶束; 向胶束中加入二价金属的卤化物或乙酸酯以及碱金属的碳酸盐或磷酸盐，使得前者与后者的摩尔比为1:0至1:1.0，由此沉积多价金属的无机盐的涂层 在胶束的表面上; 并将所得纳米粒子的平均粒径调整为5〜300nm。 多价金属的无机盐可以是碳酸钙，碳酸锌或磷酸钙。

    Composition containing retinoic acid nanoparticles coated with inorganic salt of polyvalent metal
    7.
    发明申请
    Composition containing retinoic acid nanoparticles coated with inorganic salt of polyvalent metal 审中-公开
    包含用多价金属的无机盐涂覆的视黄酸纳米粒子的组合物

    公开(公告)号：US20070258926A1

    公开(公告)日：2007-11-08

    申请号：US10595413

    申请日：2003-10-15

    申请人： Yoko Yamaguchi ,  Rie Igarashi ,  Yutaka Mizushima ,  Mitsuko Takenaga ,  Natsumi Nakamura

    发明人： Yoko Yamaguchi ,  Rie Igarashi ,  Yutaka Mizushima ,  Mitsuko Takenaga ,  Natsumi Nakamura

    IPC分类号： A61K8/04

    CPC分类号： A61K8/0241 ,  A61K8/0291 ,  A61K8/671 ,  A61K9/501 ,  A61K9/5115 ,  A61K2800/413 ,  A61K2800/621 ,  A61Q19/00 ,  A61Q19/08 ,  B82Y5/00

    摘要： A composition contains nanoparticles of retinoic acid as an active ingredient. The nanoparticles have reduced irritancy of retinoic acid and are suitable for subcutaneous or intravenous administration, as well as for use in sustained-release preparation. The high skin permeability of the nanoparticles makes the composition suitable for use in pharmaceutical or non-pharmaceutical external preparations or cosmetics intended for skin application. The retinoic acid nanoparticles of the present invention are coated with an inorganic salt of polyvalent metal and can be dissolved in water to make a stable clear solution that can be formulated into injectable preparations for subcutaneous and intravenous administration. The polyvalent metal inorganic salt coating helps reduce the irritancy of retinoic acid, so that the nanoparticles do not cause inflammation or tumor formation at the site of application. The inorganic salt of polyvalent metal may be calcium carbonate, zinc carbonate or calcium phosphate.

    摘要翻译： 组合物含有视黄酸的纳米颗粒作为活性成分。 纳米颗粒具有降低视黄酸的刺激性，适用于皮下或静脉内施用，以及用于持续释放制剂。 纳米颗粒的高皮肤渗透性使得该组合物适用于用于皮肤应用的药物或非药物外用制剂或化妆品。 本发明的视黄酸纳米粒子涂覆有多价金属的无机盐，可以溶解在水中，形成稳定的透明溶液，将其配制成用于皮下和静脉内给药的可注射制剂。 多价金属无机盐涂层有助于降低视黄酸的刺激性，使得纳米颗粒在施用部位不引起炎症或肿瘤形成。 多价金属的无机盐可以是碳酸钙，碳酸锌或磷酸钙。

    Modified BDNF
    8.
    发明授权
    Modified BDNF 失效
    改性BDNF

    公开(公告)号：US06800607B2

    公开(公告)日：2004-10-05

    申请号：US10220315

    申请日：2002-08-29

    申请人： Rie Igarashi ,  Yutaka Mizushima ,  Mutsuo Taiji ,  Chikao Nakayama ,  Hiroshi Noguchi

    发明人： Rie Igarashi ,  Yutaka Mizushima ,  Mutsuo Taiji ,  Chikao Nakayama ,  Hiroshi Noguchi

    IPC分类号： A61K3816

    CPC分类号： C07K14/475 ,  A61K38/00

    摘要： Modified BDNF having improved pharmacological activities, pharmacokinetics and physical properties can be obtained by modifying BDNF with a 1-acyl-glycerol derivative. This BDNF being modified with a 1-acyl-glycerol derivative of the present invention has more efficacious and more excellent pharmacokinetic properties with retaining the useful effects being characteristic to BDNF which are useful as remedies for neurodegenerative diseases and diabetes mellitus, and hence, it is particularly useful as a therapeutic agent for treatment of type 2 diabetes mellitus.

    摘要翻译： 通过用1-酰基 - 甘油衍生物改性BDNF可以获得具有改善的药理活性，药代动力学和物理性能的改性BDNF。 用本发明的1-酰基 - 甘油衍生物修饰的BDNF具有更有效和更优异的药代动力学性质，保留了BDNF特有的有效作用，可作为神经变性疾病和糖尿病的治疗方法，因此， 特别可用作治疗2型糖尿病的治疗剂。