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    Sustained-release preparation and process for producing the same
    1.
    发明授权
    Sustained-release preparation and process for producing the same 失效
    缓释制剂及其制备方法

    公开(公告)号：US07220430B2

    公开(公告)日：2007-05-22

    申请号：US10182239

    申请日：2001-01-26

    申请人： Takashi Ishibashi ,  Kengo Ikegami ,  Keigo Nagao ,  Hiroyuki Yoshino ,  Masakazu Mizobe

    发明人： Takashi Ishibashi ,  Kengo Ikegami ,  Keigo Nagao ,  Hiroyuki Yoshino ,  Masakazu Mizobe

    IPC分类号： A61K9/24 ,  A61K9/22 ,  A61K9/28 ,  A61K9/30 ,  A61K9/42

    CPC分类号： A61K9/2886 ,  A61K9/282 ,  A61K9/2833 ,  A61K9/2866 ,  A61K9/5015 ,  A61K9/5031 ,  A61K9/5047 ,  A61K9/5073

    摘要： The present invention is to provide a sustained release preparation comprising a drug-containing core substance and a multilayered coating layer covering the core substance, wherein all adjacent layers in the multilayered coating layer contain mutually different hydrophobic organic compound-water-soluble polymer mixtures; and, a method of producing a sustained release preparation, having a multilayered coating layer in which adjacent layers contain different hydrophobic organic compound-water-soluble polymer mixtures, which comprises spray-coating a solution containing a hydrophobic organic compound-water-soluble polymer mixture onto a drug-containing core substance, continuing to spray-coat a solution containing a different hydrophobic organic compound-water-soluble polymer mixture onto the resulting coating layer, and repeating this step.

    摘要翻译： 本发明提供一种包含药物核心物质和覆盖核心物质的多层涂层的缓释制剂，其中多层涂层中的所有相邻层含有相互不同的疏水性有机化合物 - 水溶性聚合物混合物; 以及制备缓释制剂的方法，其具有多层涂层，其中相邻层含有不同的疏水性有机化合物 - 水溶性聚合物混合物，其包括喷涂包含疏水性有机化合物 - 水溶性聚合物混合物的溶液 向含药物的核心物质上继续将含有不同的疏水性有机化合物 - 水溶性聚合物混合物的溶液喷雾到所得涂层上，并重复该步骤。

    Preparation method of drug-containing spherical fine particles
    3.
    发明授权
    Preparation method of drug-containing spherical fine particles 失效
    含药球形微粒的制备方法

    公开(公告)号：US06692768B1

    公开(公告)日：2004-02-17

    申请号：US09830345

    申请日：2001-04-26

    申请人： Takashi Ishibashi ,  Keigo Nagao ,  Kengo Ikegami ,  Hiroyuki Yoshino ,  Masakazu Mizobe

    发明人： Takashi Ishibashi ,  Keigo Nagao ,  Kengo Ikegami ,  Hiroyuki Yoshino ,  Masakazu Mizobe

    IPC分类号： A61K916

    CPC分类号： A61K9/1694 ,  A61K9/1652 ,  A61K9/5015 ,  A61K9/5047 ,  B01J2/10 ,  B01J2/14

    摘要： The present invention discloses an efficient preparation method of spherical fine particles containing a drug for an easily-swallowed, controlled-release preparation comprising the production of drug-containing spherical fine particles (mean particle size: 60-200 &mgr;m) by adding a binder solution to a mixture containing an excipient powder having the property of retaining solvent (and preferably having a mean length of the long axis of 40 &mgr;m or less) and a drug powder (preferably having a mean length of the long axis of 50 &mgr;m or less), followed by high-speed mixing granulation.

    摘要翻译： 本发明公开了一种含有容易吞咽的控释制剂的药物的球状微粒的有效制备方法，其包括通过添加粘合剂溶液来制备含药球形微粒（平均粒径：60〜200μm） 具有保持溶剂（优选长轴长度为40μm以下）的特性的赋形剂粉末和药物粉末（优选长轴的平均长度为50μm以下）的混合物， ，然后进行高速混合造粒。

    Pharmaceutical preparation in form of coated capsule releasable at lower part of digestive tract
    4.
    发明授权
    Pharmaceutical preparation in form of coated capsule releasable at lower part of digestive tract 失效
    消毒道下部可释放的涂层胶囊形式的药物制剂

    公开(公告)号：US06309666B1

    公开(公告)日：2001-10-30

    申请号：US08680753

    申请日：1996-07-15

    申请人： Harumi Hatano ,  Takahiro Ito ,  Takashi Ishibashi ,  Hiroyuki Yoshino ,  Masakazu Mizobe

    发明人： Harumi Hatano ,  Takahiro Ito ,  Takashi Ishibashi ,  Hiroyuki Yoshino ,  Masakazu Mizobe

    IPC分类号： A61K952

    CPC分类号： A61K9/4891

    摘要： A pharmaceutical preparation in the form of a coated capsule which can release contents of a capsule at a lower part of the digestive tract comprising (a) a hard capsule containing at least an acidic substance, (b) a polymer film soluble at low pH which is formed on a surface of said hard capsule, and (c) an enteric coating film which is formed on a surface of said polymer film soluble at low pH. According to the pharmaceutical preparation of the present invention, any kind of a medicament can be delivered to any desired site between the upper part of the small intestine and the lower part of the large intestine in the digestive tract by controlling the amount of polymer(s) used for the polymer film soluble at low pH and/or by selecting the kind of the polymer film soluble at low pH and/or the acidic substance without any complicated requirements for each medicament.

    摘要翻译： 一种涂层胶囊形式的药物制剂，其能够释放消化道下部的胶囊内含物，其包含（a）含有至少一种酸性物质的硬胶囊，（b）在低pH下可溶的聚合物膜， 形成在所述硬胶囊的表面上，和（c）形成在所述聚合物膜的表面上的可溶于低pH的肠溶衣膜。 根据本发明的药物制剂，通过控制聚合物的量（s），可以将任何种类的药物递送到消化道的小肠上部和大肠的下部之间的任意位置 ）和/或通过选择在低pH下可溶解的聚合物膜的种类和/或酸性物质，而对每种药物没有任何复杂的要求。

    Preparation capable of releasing drug at target site in intestine
    5.
    发明授权
    Preparation capable of releasing drug at target site in intestine 有权
    能够在肠道靶点释放药物的制剂

    公开(公告)号：US06638534B1

    公开(公告)日：2003-10-28

    申请号：US09744653

    申请日：2001-01-29

    申请人： Takashi Ishibashi ,  Hiroaki Kubo ,  Hiroyuki Yoshino ,  Masakazu Mizobe

    发明人： Takashi Ishibashi ,  Hiroaki Kubo ,  Hiroyuki Yoshino ,  Masakazu Mizobe

    IPC分类号： A61K922

    CPC分类号： A61K9/5078

    摘要： A preparation capable of releasing a medicinal substance at a targeted site in the intestine, wherein the preparation dose not releases medicinal substance in endogastri at all, but can quickly release a medicinal substance when it reaches the desired site in the intestine after a certain period of time from discharge of the preparation from the stomach, and wherein a core material containing a medicinal substance is coated with a mixed film of a hydrophobic organic compound—an enteric polymer. The preparation is useful for a local therapy of inflammatory disease in the intestine such as ulcerative colitis or Crohn's disease, or an oral administrative therapy with a medicinal substance of a peptide which is apt to be decomposed chemically or enzymatically in any site except for a specific site in the intestine such as the large intestine, or with a medicinal substance whose absorption site in the intestine is limited, or the like, because a medicinal substance can be delivered selectively to a specific site in the intestine.

    摘要翻译： 一种能够在肠内靶向部位释放药物的制剂，其中所述制剂剂量根本不会释放内吞食物中的药物，但在经过一定时间后到达肠道的期望部位时能迅速释放药用物质 由制剂从胃排出的时间，并且其中含有药物的核心材料涂覆有疏水性有机化合物 - 肠溶性聚合物的混合膜。 该制剂可用于肠道炎症性疾病如溃疡性结肠炎或克罗恩病的局部治疗，或用于药物物质的口服行政治疗，该药物物质易于在任何位置化学或酶促分解，除了特定的 因为药物物质可以选择性地递送到肠道的特定部位，因此肠道如大肠中的部位或肠内吸收部位受限的药物等。

    Process for producing di(aryloxy)alkane
    7.
    发明授权
    Process for producing di(aryloxy)alkane 失效
    制备二（芳氧基）烷烃的方法

    公开(公告)号：US5041604A

    公开(公告)日：1991-08-20

    申请号：US540872

    申请日：1990-06-20

    申请人： Toranosuke Saito ,  Masakatu Kitani ,  Takashi Ishibashi

    发明人： Toranosuke Saito ,  Masakatu Kitani ,  Takashi Ishibashi

    IPC分类号： C07C65/21 ,  B01J23/02 ,  C07B31/00 ,  C07B41/04 ,  C07B61/00 ,  C07C41/00 ,  C07C41/01 ,  C07C41/16 ,  C07C43/20 ,  C07C45/00 ,  C07C49/84 ,  C07C51/00 ,  C07C67/00 ,  C07C201/00 ,  C07C201/12 ,  C07C205/38 ,  C07C253/00 ,  C07C253/30 ,  C07C255/37 ,  C07C255/54

    CPC分类号： C07C41/16

    摘要： A process for producing a high quality di(aryloxy)alkane with a high yield by the use of readily commercially available materials, without using any particular solvent or agent and by means of a simple operation and a general apparatus is provided, which process comprises subjecting a halogenated alkane of the formula (II)X--A--Y (II)wherein X and Y each represent a halogen atom and A represents a lower alkylene group, and a phenol of the formula (III) ##STR1## wherein R.sub.1 to R.sub.5 each are same or different, represent hydrogen, halogen, lower alkyl, lower alkoxy, carboxylic acid salt, acyl or nitro group, and may form a ring in conjunction of two adjacent groups,to condensation reaction in the presence of an alkali in an aqueous medium to form a di(aryloxy)alkane of the formula (I) ##STR2## and is characterized (i) by carrying out the condensation reaction in a molar ratio of the compound of the formula (II): the phenol of the formula (III): the alkali in terms of monovalent base of 1:1.5 to 3.0:1.5 to 3.0; or(ii) by carrying out the condensation reaction of the above (i) and adjusting the quantity of the aqueous medium phase after completion of the reaction can be 35% or less based on the oily phase; or(iii) by carrying out the condensation reaction of the above (i), feeding at least the alkali among the reaction components with progress of the reaction and adjusting the quantity of the aqueous medium phase as described in the above (ii).

    摘要翻译： 提供了一种通过使用容易商业化的材料生产高质量的二（芳氧基）烷烃的方法，而不使用任何特定的溶剂或试剂，并且通过简单的操作和一般的设备，该方法包括 式（II）XAY（II）的卤化烷烃，其中X和Y各自表示卤素原子，A表示低级亚烷基，和式（III）的苯酚（III）其中R1至R5各自 相同或不同，表示氢，卤素，低级烷基，低级烷氧基，羧酸盐，酰基或硝基，并且可以与两个相邻基团结合形成环，在碱的存在下在水性介质中进行缩合反应 形成式（I）的二（芳氧基）烷烃（I），其特征在于（i）通过以式（II）的化合物与式（II）的苯酚的摩尔比进行缩合反应： 式（III）：以碱为一价碱 为1：1.5至3.0：1.5至3.0; 或者（ii）通过进行上述（i）的缩合反应，并且在反应完成后调整水介质相的量可以基于油相为35％以下。 或者（iii）通过进行上述（i）的缩合反应，至少将反应成分中的碱与反应进行同时进行，并且如上述（ii）所述调节水相介质相的量。