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    SUSTAINED-RELEASE NANOPARTICLE CONTAINING LOW-MOLECULAR-WEIGHT DRUG WITH NEGATIVELY CHARGED GROUP
    2.
    发明申请
    SUSTAINED-RELEASE NANOPARTICLE CONTAINING LOW-MOLECULAR-WEIGHT DRUG WITH NEGATIVELY CHARGED GROUP 审中-公开
    含有低分子量药物的含有低分子量药物的持续释放纳米颗粒

    公开(公告)号：US20100129456A1

    公开(公告)日：2010-05-27

    申请号：US12597969

    申请日：2008-04-11

    申请人： Tsutomu Ishihara ,  Yutaka Mizushima ,  Ayako Mizushima ,  Toru Mizushima

    发明人： Tsutomu Ishihara ,  Yutaka Mizushima ,  Ayako Mizushima ,  Toru Mizushima

    IPC分类号： A61K9/14

    CPC分类号： A61K9/5153 ,  A61K9/19 ,  A61K9/5192 ,  A61K31/00 ,  A61K45/06

    摘要： A nanoparticle containing a low-molecular-weight drug having a negatively charged group is provided that is effectively targeted to an affected site, is capable of sufficiently sustained release of the drug, and has a reduced tendency to accumulate in the liver to cause reduced side effects. The nanoparticle containing a low-molecular-weight drug having a negatively charged group is obtained by hydrophobicizing the low-molecular-weight drug having a negatively charged group with a metal ion, and reacting the hydrophobicized drug with poly L-lactic acid or poly(L-lactic acid/glycolic acid) copolymer and poly DL- or L-lactic acid-polyethylene glycol block copolymer or poly(DL- or L-lactic acid/glycolic acid)-polyethylene glycol block copolymer.

    摘要翻译： 提供了含有具有带负电荷的基团的低分子量药物的纳米粒子，其有效靶向受影响部位，能够充分持续释放药物，并且具有减少的积聚在肝脏中的趋势，导致减少的侧面 效果。 含有带负电荷基团的低分子量药物的纳米粒子是通过用金属离子疏水化具有带负电荷的基团的低分子量药物，并使疏水化药物与聚-L-乳酸或聚（ L-乳酸/乙醇酸）共聚物和聚DL-或L-乳酸 - 聚乙二醇嵌段共聚物或聚（DL-或L-乳酸/乙醇酸） - 聚乙二醇嵌段共聚物。

    Intravenous composition, process for producing the same and preparation thereof
    3.
    发明申请
    Intravenous composition, process for producing the same and preparation thereof 审中-公开
    静脉内组合物，制备方法及其制备方法

    公开(公告)号：US20060088598A1

    公开(公告)日：2006-04-27

    申请号：US10514435

    申请日：2003-05-27

    申请人： Yutaka Mizushima ,  Tsutomu Ishihara

    发明人： Yutaka Mizushima ,  Tsutomu Ishihara

    IPC分类号： A61K9/50 ,  A61K9/16 ,  A61K31/573 ,  A61K31/557

    CPC分类号： A61K31/573 ,  A61K9/1647 ,  A61K31/5575

    摘要： A composition for intravenous injection, which gradually decomposed instead of fat particles, has sufficient sustained release effects, has an excellent encapsulation ratio of lipid-soluble agents, and has such sustained release effects at lesion sites; a production method thereof; and a preparation containing the composition. The composition for intravenous injection is produced by encapsulating a prostanoid or steroid in a poly(lactic-co-glycolic acid) or poly(lactic acid) microparticle, and allowing lecithin or similar surfactant to be adsorbed on the surface or the above poly(lactic-co-glycolic acid) or poly(lactic acid) microparticle. A method for producing the composition comprises: dissolving esterified prostanoic acid or esterified steroid and a poly(lactic-co-glycolic acid) or poly(lactic acid) in an organic solvent such as dichloromethane or dimethylsulfoxide; and emulsilfying the obtained mixture in water, using the lecithin or similar surfactant capable of adjusting the diameter of the copolymer or particle to between 50 and 500 nm, employing an ultrasonic generator, a Polytron Homogenizer, or the like.

    摘要翻译： 用于静脉注射的组合物，其逐渐分解代替脂肪颗粒，具有足够的缓释作用，具有优异的脂溶性试剂的包封率，并且在病变部位具有这种持续释放作用; 其制造方法; 和含有该组合物的制剂。 用于静脉注射的组合物通过将前列腺素类或类固醇包封在聚（乳酸 - 共 - 乙醇酸）或聚（乳酸）微粒中而制备，并且使卵磷脂或类似表面活性剂吸附在表面或上述聚（乳酸） 乙醇酸）或聚（乳酸）微粒。 制备组合物的方法包括：将酯化的前列腺酸或酯化的类固醇和聚（乳酸 - 共 - 乙醇酸）或聚（乳酸）溶解在有机溶剂如二氯甲烷或二甲基亚砜中; 并使用超声波发生器，Polytron均质器等将能够调节共聚物或颗粒的直径的卵磷脂或类似表面活性剂在水中乳化成50-500nm。

    Drug-containing nanoparticle, process for producing the same and parenterally administered preparation from the nanoparticle
    4.
    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。

    Intravenous nanoparticles for targeting drug delivery and sustained drug release
    5.
    发明申请
    Intravenous nanoparticles for targeting drug delivery and sustained drug release 审中-公开
    用于靶向药物递送和持续释放药物的静脉内纳米颗粒

    公开(公告)号：US20060233883A1

    公开(公告)日：2006-10-19

    申请号：US10550990

    申请日：2004-03-11

    申请人： Tsutomu Ishihara ,  Yutaka Mizushima

    发明人： Tsutomu Ishihara ,  Yutaka Mizushima

    IPC分类号： A61K9/50 ,  A61K33/24 ,  A61K33/34 ,  A61K9/16 ,  A61K33/26 ,  A61K31/573

    CPC分类号： A61K9/5153 ,  A61K9/5192

    摘要： Provided are poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) nanoparticles that encapsulate a low molecular weight and water-soluble drug and can deliver the drug to target legion sites where the particles gradually release the drug over a prolonged period of time. The nanoparticles are prepared by allowing the low-molecular, water-soluble and non-peptide drug to interact with a metal ion so as to make the drug hydrophobic, encapsulating the hydrophobicized drug into PLGA or PLA nanoparticles, and allowing a surfactant to be adsorbed onto the surface of the particles.

    摘要翻译： 提供了包封低分子量和水溶性药物的聚（乳酸 - 共 - 乙醇酸）（PLGA）和聚（乳酸）（PLA）纳米颗粒，并且可以将药物递送到靶颗粒位置，其中颗粒逐渐释放 药物长时间使用。 通过使低分子，水溶性和非肽药物与金属离子相互作用以使药物疏水化，将疏水化药物包封到PLGA或PLA纳米颗粒中并允许表面活性剂被吸附来制备纳米颗粒 到颗粒表面。

    Signal conversion circuit
    6.
    发明授权
    Signal conversion circuit 失效
    信号转换电路

    公开(公告)号：US4611129A

    公开(公告)日：1986-09-09

    申请号：US603113

    申请日：1984-04-23

    申请人： Tsutomu Ishihara

    发明人： Tsutomu Ishihara

    IPC分类号： G01L9/06 ,  H04R3/00 ,  H01C7/06

    CPC分类号： G01L9/06

    摘要： An electronic circuit uses a two input operational amplifier for converting a pressure into an electrical signal. The bias potentials at the two inputs are equal to each other in the absence of pressure. The bias potential is applied to one input via a pressure sensitive resistor comprising a semiconductor diaphram with a resistance diffused thereon. When pressure appears, the resistance changes and there is a difference of potential at the two inputs, which is processed into the electrical signal.

    摘要翻译： 电子电路使用两输入运算放大器将压力转换成电信号。 两个输入端的偏置电位在没有压力的情况下彼此相等。 偏置电位通过包含在其上扩散的电阻的半导体层的压敏电阻施加到一个输入端。 当出现压力时，电阻变化，两个输入端的电位差异被加工成电信号。

    NANOPARTICLE CONTAINING PROSTAGLANDIN I 2 DERIVATIVE
    7.
    发明申请
    NANOPARTICLE CONTAINING PROSTAGLANDIN I 2 DERIVATIVE 有权
    含有PROSTAGLANDIN I 2衍生物的纳米颗粒

    公开(公告)号：US20140050690A1

    公开(公告)日：2014-02-20

    申请号：US13984556

    申请日：2012-02-13

    申请人： Toru Mizushima ,  Tsutomu Ishihara ,  Hongxing Liu

    发明人： Toru Mizushima ,  Tsutomu Ishihara ,  Hongxing Liu

    IPC分类号： A61K47/48 ,  A61K31/343

    CPC分类号： A61K47/48215 ,  A61K9/51 ,  A61K31/5585 ,  A61K47/30 ,  A61K47/34 ,  A61K47/593 ,  A61K47/60 ,  A61K47/6937

    摘要： There is provided a beraprost sodium-containing nanoparticle that contains beraprost sodium among other prostaglandin I2 (prostacyclin) derivatives, which are therapeutic agents for pulmonary hypertension. The beraprost sodium-containing nanoparticle is obtained by making beraprost sodium hydrophobic using a metal ion and allowing the hydrophobic beraprost sodium to react with poly-L-lactic acid or a poly(L-lactic acid/glycolic acid) copolymer, and a poly-DL- or L-lactic acid-polyethylene glycol block copolymer or a poly(DL- or L-lactic acid/glycolic acid)-polyethylene glycol block copolymer. The beraprost sodium-containing nanoparticle excels in sustained release of an active ingredient, reduces a side effect, and furthermore, has an excellent drug retention in the blood. Therefore, the beraprost sodium-containing nanoparticle is quite outstanding particularly regarding the sustainability of the medicinal effect.

    摘要翻译： 提供了含有贝前列素钠的贝前列素钠纳米颗粒，其中前列腺素I2（前列环素）衍生物是肺动脉高压的治疗剂。 通过使用金属离子制备贝前列素钠疏水性并使疏水性贝前列素钠与聚-L-乳酸或聚（L-乳酸/乙醇酸）共聚物反应，获得贝前列素含钠纳米颗粒， DL-或L-乳酸 - 聚乙二醇嵌段共聚物或聚（DL-或L-乳酸/乙醇酸） - 聚乙二醇嵌段共聚物。 所述贝前列素含钠纳米粒子优选活性成分的持续释放，减少副作用，并且在血液中具有优异的药物保留性。 因此，贝拉前列素含钠纳米颗粒在药效的可持续性方面尤为突出。

    Nanoparticle containing prostaglandin I2 derivative
    8.
    发明授权
    Nanoparticle containing prostaglandin I2 derivative 有权
    含有前列腺素I2衍生物的纳米粒子

    公开(公告)号：US09161986B2

    公开(公告)日：2015-10-20

    申请号：US13984556

    申请日：2012-02-13

    申请人： Toru Mizushima ,  Tsutomu Ishihara ,  Hongxing Liu

    发明人： Toru Mizushima ,  Tsutomu Ishihara ,  Hongxing Liu

    IPC分类号： A61K31/5585 ,  A61K9/51 ,  A61K47/34 ,  A61K47/48 ,  A61K47/30 ,  A61K31/343

    CPC分类号： A61K47/48215 ,  A61K9/51 ,  A61K31/5585 ,  A61K47/30 ,  A61K47/34 ,  A61K47/593 ,  A61K47/60 ,  A61K47/6937

    摘要： There is provided a beraprost sodium-containing nanoparticle that contains beraprost sodium among other prostaglandin I2 (prostacyclin) derivatives, which are therapeutic agents for pulmonary hypertension. The beraprost sodium-containing nanoparticle is obtained by making beraprost sodium hydrophobic using a metal ion and allowing the hydrophobic beraprost sodium to react with poly-L-lactic acid or a poly(L-lactic acid/glycolic acid) copolymer, and a poly-DL- or L-lactic acid-polyethylene glycol block copolymer or a poly(DL- or L-lactic acid/glycolic acid)-polyethylene glycol block copolymer. The beraprost sodium-containing nanoparticle excels in sustained release of an active ingredient, reduces a side effect, and furthermore, has an excellent drug retention in the blood. Therefore, the beraprost sodium-containing nanoparticle is quite outstanding particularly regarding the sustainability of the medicinal effect.

    摘要翻译： 提供了含有贝前列素钠的贝前列素钠纳米颗粒，其中前列腺素I2（前列环素）衍生物是肺动脉高压的治疗剂。 通过使用金属离子制备贝前列素钠疏水性并使疏水性贝前列素钠与聚-L-乳酸或聚（L-乳酸/乙醇酸）共聚物反应，获得贝前列素含钠纳米颗粒， DL-或L-乳酸 - 聚乙二醇嵌段共聚物或聚（DL-或L-乳酸/乙醇酸） - 聚乙二醇嵌段共聚物。 所述贝前列素含钠纳米粒子优选活性成分的持续释放，减少副作用，并且在血液中具有优异的药物保留性。 因此，贝拉前列素含钠纳米颗粒在药效的可持续性方面尤为突出。