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    Process for making carbapenem compounds
    4.
    发明授权
    Process for making carbapenem compounds 有权
    制备碳青霉烯类化合物的方法

    公开(公告)号：US07022841B2

    公开(公告)日：2006-04-04

    申请号：US10485134

    申请日：2002-09-20

    申请人： Raymond Cvetovich ,  Robert Wenslow ,  John M. Williams ,  Daniel Sidler ,  Louis Crocker ,  Hsien-Hsin Tung ,  Brian K. Johnson ,  Joseph Kukura, II ,  Ulf Dolling

    发明人： Raymond Cvetovich ,  Robert Wenslow ,  John M. Williams ,  Daniel Sidler ,  Louis Crocker ,  Hsien-Hsin Tung ,  Brian K. Johnson ,  Joseph Kukura, II ,  Ulf Dolling

    IPC分类号： C07D477/20

    CPC分类号： C07D477/20 ,  C07D477/02

    摘要： The present invention relates to a process for reducing the levels of organic solvents to pharmaceutically acceptable levels in thermally unstable crystalline carbapenem solids represented by formula I: or a salt thereof, wherein R1 and R2, are the same or different, and are selected from H, alkyl, aryl, and heteroaryl, comprising washing a carbapenem solid containing organic solvent with an organic solvent containing water; and using vacuum and/or inert gas (hydrated or dry) at low temperature to produce a compound of formula I containing pharmaceutically acceptable levels of organic solvents, wherein the water content of the crystalline carbapenem solid, correcting for organic solvents, is maintained at about 13% to about 25% during the process.

    摘要翻译： 本发明涉及一种将由式I表示的热不稳定结晶碳青霉烯固体中的有机溶剂水平降低到可药用水平的方法：或其盐，其中R 1和R 2 包括相同或不同的选自H，烷基，芳基和杂芳基，包括用含水的有机溶剂洗涤含有有机溶剂的碳青霉烯固体; 并在低温下使用真空和/或惰性气体（水合或干燥）以产生含有药学上可接受水平的有机溶剂的式I化合物，其中将有机溶剂校正的结晶碳青霉烯固体的水含量保持在约 13％至25％。

    High drug loading pharmaceutical compositions
    5.
    发明授权
    High drug loading pharmaceutical compositions 有权

    公开(公告)号：US10792249B2

    公开(公告)日：2020-10-06

    申请号：US15803372

    申请日：2017-11-03

    申请人： Hsien-Hsin Tung

    发明人： Hsien-Hsin Tung

    IPC分类号： A61K9/10 ,  A61K9/14 ,  A61K31/192 ,  G01N25/48

    摘要： A pharmaceutical composition of high drug loading comprising an active pharmaceutical ingredient (API) and pharmaceutical acceptable additives, which include glass-solution forming additive and/or eutectic-mixture forming additive, is provided. The composition is dispersed uniformly to form a hybrid solid dispersion consisting of crystalline-suspension, glass-solution and/or eutectic-mixture, where the crystalline API is uniformly distributed in the hybrid solid dispersion and exists in nano/micro particle size range. The amorphous API, when present, is uniformly distributed in the hybrid solid dispersion. The API may exist in different chemical and/or physical forms. The API is present in an amount of from more than about 50% wt/wt to about 90% wt/wt with respect to the total amount of the active pharmaceutical ingredient and the pharmaceutically acceptable glass-solution forming and/or eutectic-mixture forming additives. At least about 50% wt/wt of the API is dispersed in the crystalline-suspension and at least about 5% wt/wt of the API is dispersed in the glass-solution and/or eutectic-mixture. The pharmaceutical composition offers excellent dissolution rate, superior chemical and physical stability, and minimum drug-drug/drug-excipient incompatibility. The composition is beneficial for reducing the overall tablet/capsule size for low water-soluble drugs requiring high drug loading or dosage, including combination drugs.

    NANOPARTICLE FORMATION VIA RAPID PRECIPITATION
    6.
    发明申请
    NANOPARTICLE FORMATION VIA RAPID PRECIPITATION 审中-公开
    通过快速降解的纳米颗粒形成

    公开(公告)号：US20110053927A1

    公开(公告)日：2011-03-03

    申请号：US12989148

    申请日：2009-04-20

    申请人： Hsien-Hsin Tung ,  Lei Wang ,  Santipharp Panmai ,  Michael Riebe

    发明人： Hsien-Hsin Tung ,  Lei Wang ,  Santipharp Panmai ,  Michael Riebe

    IPC分类号： A61K31/5377 ,  A61P1/08 ,  A61K9/14 ,  B01J19/10 ,  B82Y40/00

    CPC分类号： A61K9/5161 ,  A61K9/14 ,  A61K9/1688 ,  A61K9/1694 ,  A61K9/5192 ,  B01D9/0054 ,  B01F5/0256 ,  B01F5/10 ,  B01F11/0258 ,  B01F13/1027

    摘要： The invention encompasses a method for making nano-sized particles of water-insoluble pharmaceuticals comprising: (1) dissolving the water-insoluble pharmaceutical in a water-miscible solvent, optionally with water and inactive pharmaceutical ingredients, to make a solution; (2) rapidly mixing the solution with an anti-solvent which creates a high level of supersaturation, wherein the anti-solvent is water with optional inactive pharmaceutical ingredients; (3) simultaneously applying energy to the resulting mixture during the mixing of solution and anti-solvent as nano-sized drug particles precipitate out and form a slurry mixture under supersaturation; and (4) optionally isolating the nano-sized particles of water-insoluble pharmaceuticals from the slurry mixture.

    摘要翻译： 本发明包括制备水不溶性药物的纳米尺寸颗粒的方法，包括：（1）将水不溶性药物溶解在水混溶性溶剂中，任选地用水和非活性药物成分溶解; （2）将溶液与抗溶剂快速混合，产生高水平的过饱和度，其中抗溶剂是具有任选的非活性药物成分的水; （3）在溶液和反溶剂混合过程中同时向所得混合物施加能量作为纳米尺寸药物颗粒沉淀出来，并在过饱和下形成浆料混合物; 和（4）任选地从浆料混合物中分离纳米尺寸的水不溶性药物颗粒。