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    THERAPEUTIC COMPOSITION FOR INTERSTITUAL PNEUMONIA
    2.
    发明申请
    THERAPEUTIC COMPOSITION FOR INTERSTITUAL PNEUMONIA 审中-公开
    间接肺炎的治疗组合物

    公开(公告)号：US20100143321A1

    公开(公告)日：2010-06-10

    申请号：US12519437

    申请日：2007-12-19

    申请人： Kouji Shirai ,  Tatsuo Kawashima ,  Toshihisa Kuroda ,  Yutaka Mizushima ,  Ayako Mizushima ,  Masahiro Murakami ,  Tomoharu Fukuzaki

    发明人： Kouji Shirai ,  Tatsuo Kawashima ,  Toshihisa Kuroda ,  Yutaka Mizushima ,  Ayako Mizushima ,  Masahiro Murakami ,  Tomoharu Fukuzaki

    IPC分类号： A61K38/44 ,  A61P11/00

    CPC分类号： A61K31/573 ,  A61K9/0019 ,  A61K38/00 ,  A61K47/26 ,  A61K47/544 ,  C12N9/0089

    摘要： A therapeutic agent for interstitial pneumonia is provided which effectively exploits the effect of superoxide dismutase (SOD). The therapeutic composition for interstitial pneumonia contains 10 to 100 mg of lecithinized superoxide dismutase represented by the following general formula (I): SOD′(Q-B)m   (I) (wherein SOD′ is a residue of superoxide dismutase; Q is a chemical crosslink; B is a residue of lysolecithin having the hydrogen atom of the hydroxyl group at position 2 of its glycerol moiety removed; and m is the average number of lysolecithin molecules bound to one molecule of the superoxide dismutase and is an integer of 1 or greater) and further contains sucrose to give it a stable form suitable for intravenous administration.

    摘要翻译： 提供间质性肺炎治疗剂，有效利用超氧化物歧化酶（SOD）的作用。 间质性肺炎的治疗组合物含有10-100mg由以下通式（I）表示的卵磷脂化超氧化物歧化酶：SOD'（QB）m（I）（其中SOD'是超氧化物歧化酶的残基; Q是化学交联 ; B是除去其甘油部分的位置2处的羟基的氢原子的溶血卵磷脂的残基; m是与1分子超氧化物歧化酶结合的溶血卵磷脂分子的平均数，为1以上的整数） 并且还含有蔗糖以使其具有适于静脉内施用的稳定形式。

    SUSTAINED-RELEASE NANOPARTICLE CONTAINING LOW-MOLECULAR-WEIGHT DRUG WITH NEGATIVELY CHARGED GROUP
    3.
    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
    4.
    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
    5.
    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
    7.
    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。

    Method of controlling paticle size of retinoic acid nanoparticles coated with polyvalent metal inorganic salt and nanoparticles obtained by the controlling method
    9.
    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。

    Sustained-release composition process for producing the same and preparation thereof
    10.
    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。