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    SUSTAINED-RELEASE NANOPARTICLE CONTAINING LOW-MOLECULAR-WEIGHT DRUG WITH NEGATIVELY CHARGED GROUP
    11.
    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。

    Zinc-containing sustained-release composition, its preparation, and method for producing the same
    12.
    发明授权
    Zinc-containing sustained-release composition, its preparation, and method for producing the same 失效
    含锌缓释组合物及其制备方法及其制备方法

    公开(公告)号：US07642230B2

    公开(公告)日：2010-01-05

    申请号：US10555191

    申请日：2004-04-01

    申请人： Michio Kimura ,  Tomoko Eto ,  Yutaka Mizushima

    发明人： Michio Kimura ,  Tomoko Eto ,  Yutaka Mizushima

    IPC分类号： A61K38/02 ,  A61K33/30 ,  A61K33/42

    CPC分类号： C07K16/241 ,  A61K9/0019 ,  A61K9/10 ,  A61K33/30 ,  A61K38/193 ,  A61K38/212 ,  A61K38/27 ,  A61K45/06 ,  A61K47/02 ,  A61K2300/00

    摘要： With a simple and high-yield production method, a zinc-containing sustained-release composition capable of stabilizing a physiologically active protein or peptide, typically G-CSF by precipitation and retaining drug efficacy for several days in a living body owing to its sustained releasability is provided. Concretely, a zinc-containing sustained-release composition produced by forming a precipitate by mixing a physiologically active protein or peptide, a water-soluble zinc salt, a water-soluble carbonate and/or a water soluble phosphate aqueous solution. The zinc-containing sustained-release composition may be administered as a zinc-containing sustained preparation by adding a pharmaceutically acceptable additive as is necessary.

    摘要翻译： 通过简单且高产量的生产方法，能够通过沉淀稳定生理活性蛋白质或肽，通常为G-CSF的锌含量缓释组合物，由于其具有持续的释放性，在活体中保持药物疗效几天 被提供。 具体地说，通过混合生理活性蛋白质或肽，水溶性锌盐，水溶性碳酸盐和/或水溶性磷酸盐水溶液形成沉淀物而制备的含锌缓释组合物。 含锌持续释放组合物可以通过根据需要添加药学上可接受的添加剂作为含锌缓释制剂施用。

    Method for Screening for Compounds Safe for Gastric Mucosa
    13.
    发明申请
    Method for Screening for Compounds Safe for Gastric Mucosa 审中-公开
    筛选胃粘膜安全的化合物的方法

    公开(公告)号：US20080113014A1

    公开(公告)日：2008-05-15

    申请号：US10597483

    申请日：2004-12-15

    申请人： Toru Mizushima ,  Yutaka Mizushima

    发明人： Toru Mizushima ,  Yutaka Mizushima

    IPC分类号： A61K9/127 ,  G01N33/92 ,  A61K31/192 ,  A61K31/60 ,  A61K31/56

    CPC分类号： G01N33/5076 ,  G01N33/5008 ,  G01N33/5014 ,  G01N33/5432 ,  G01N33/582 ,  G01N33/586 ,  G01N2500/00

    摘要： A method for screening for compounds or salts thereof, in particular nonsteroidal anti-inflammatory compounds or salts thereof, that are safe for gastric mucosa and cause little gastrointestinal side effects. The method uses a particular liposome to serve as a cell membrane model. The liposome encapsulates a fluorescent dye, in particular, calcein and is formed of phospholipids, such as phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, and phosphatidylinositol. A test compound is allowed to react with the liposome and the leakage of the fluorescent dye from the liposome is evaluated. As a result, compounds safe for gastric mucosa, in particular, anti-inflammatory compounds can be screened.

    摘要翻译： 用于筛选其对胃粘膜安全并且引起很少胃肠道副作用的化合物或其盐，特别是非甾体抗炎化合物或其盐的方法。 该方法使用特定的脂质体作为细胞膜模型。 脂质体封装荧光染料，特别是钙黄绿素，并由磷脂形成，例如磷脂酰胆碱，磷脂酰甘油，磷脂酰丝氨酸和磷脂酰肌醇。 使测试化合物与脂质体反应，并评估荧光染料从脂质体的泄漏。 因此，可以筛选对胃粘膜，特别是抗炎化合物安全的化合物。

    DRUG-CONTAINING SUSTAINED RELEASE MICROPARTICLE, PROCESS FOR PRODUCING THE SAME AND PREPARATION CONTAINING THE MICROPARTICLE
    15.
    发明申请
    DRUG-CONTAINING SUSTAINED RELEASE MICROPARTICLE, PROCESS FOR PRODUCING THE SAME AND PREPARATION CONTAINING THE MICROPARTICLE 失效
    包含持续释放微生物的药物，其生产方法和含有微生物的制剂

    公开(公告)号：US20100322902A1

    公开(公告)日：2010-12-23

    申请号：US12837810

    申请日：2010-09-02

    申请人： Yutaka Mizushima ,  Yasuaki Ogawa ,  Junzo Tanaka ,  Toshiyuki Ikoma

    发明人： Yutaka Mizushima ,  Yasuaki Ogawa ,  Junzo Tanaka ,  Toshiyuki Ikoma

    IPC分类号： A61K38/21 ,  A61K47/02 ,  A61K31/573

    CPC分类号： A61K31/00 ,  A61K9/1611 ,  A61K33/30 ,  A61K33/42 ,  A61K45/06 ,  A61K2300/00

    摘要： Sustained release microparticles suitable for various types of drugs, or drug-containing sustained release microparticles capable of sustained release of drugs over a period of three days or more and capable of inhibiting initial burst release; a process for producing the same; and preparations containing the microparticles are disclosed. The drug-containing sustained release microparticles comprise a drug other than human growth hormone and a porous apatite derivative, and optionally include a water-soluble bivalent metal compound. The drug-containing sustained release microparticles can be produced by dispersing under agitation microparticles of a porous apatite derivative in an aqueous solution containing a drug so that the aqueous solution infiltrates into the porous apatite derivative; optionally adding an aqueous solution containing a water-soluble bivalent metal compound that may infiltrate into the porous apatite derivative; further adding additives such as a stabilizer to the mixture; and effecting lyophilization or vacuum drying.

    摘要翻译： 适用于各种类型药物的持续释放微粒，或能够在三天或更长时间内持续释放药物并且能够抑制初始爆发释放的药物持续释放微粒; 其制造方法; 并且公开了含有微粒的制剂。 含药物的缓释微粒包含除人生长激素以外的药物和多孔磷灰石衍生物，任选地包含水溶性二价金属化合物。 含药缓释微粒可以通过将多孔磷灰石衍生物的微粒分散在含有药物的水溶液中分散而制成，使得水溶液渗透到多孔磷灰石衍生物中; 任选地加入含有可渗透到多孔磷灰石衍生物中的水溶性二价金属化合物的水溶液; 进一步向混合物中加入稳定剂等添加剂; 并进行冻干或真空干燥。

    Sustained-release composition process for producing the same and preparation thereof
    17.
    发明申请
    Sustained-release composition process for producing the same and preparation thereof 审中-公开
    缓释组合物的制备方法及其制备方法

    公开(公告)号：US20060093670A1

    公开(公告)日：2006-05-04

    申请号：US10516122

    申请日：2003-06-09

    申请人： Yutaka Mizushima ,  Yukie Takagi ,  Tomomi Hagi ,  Toshiyuki Ikoma

    发明人： Yutaka Mizushima ,  Yukie Takagi ,  Tomomi Hagi ,  Toshiyuki Ikoma

    IPC分类号： A61K38/39 ,  A61K31/737 ,  A61K9/22

    CPC分类号： A61K9/0024 ,  A61K9/143 ,  A61K9/1611

    摘要： The present invention provides a sustained-release composition by which a sustained-release effect can be obtained for a long time when injecting microparticles of the composition in an amount that can be subcutaneously or intramuscularly injected to a human with ease and without pain. The composition comprises porous hydroxyapatite microparticles having pores embolized by filling the pores in the microparticles with a biologically active drug, a human serum protein, and a mucopolysaccharide, and adding a divalent metal ion. Alternatively, the composition comprises porous hydroxyapatite microparticles having pores embolized in the outer layer by filling the pores in the microparticles with a biologically active drug, a human serum protein, and a water-soluble calcium salt one after another or at one time, and then adding sodium carbonate, sodium hydrogen carbonate, or an aqueous carbonate ion solution.

    摘要翻译： 本发明提供了一种持续释放组合物，通过该缓释组合物，将组合物的微粒注入可以皮下或肌肉内注射的人容易且无疼痛的长时间下，可以获得持续释放作用。 该组合物包含通过用生物活性药物，人血清蛋白质和粘多糖填充微粒中的孔而堵塞孔的多孔羟基磷灰石微粒，并加入二价金属离子。 或者，组合物包含多孔羟基磷灰石微粒，其通过用生物活性药物，人血清蛋白和水溶性钙盐一次又一次或一次填充微粒中的孔，在外层中堵塞孔，然后 加入碳酸钠，碳酸氢钠或碳酸氢钠水溶液。

    Intravenous composition, process for producing the same and preparation thereof
    18.
    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。

    Intravenous nanoparticles for targeting drug delivery and sustained drug release
    20.
    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。