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1. 发明授权

US5716642A Microprecipitation of nanoparticulate pharmaceutical agents using surface active material derived from similar pharmaceutical agents 失效
标题翻译：使用衍生自相似药剂的表面活性物质微粒沉淀纳米颗粒药剂
公开(公告)号：US5716642A
公开(公告)日：1998-02-10
申请号：US370928
申请日：1995-01-10
申请人： Pranab Bagchi , Gregory L. McIntire , John R. Minter
发明人： Pranab Bagchi , Gregory L. McIntire , John R. Minter
IPC分类号： A61K9/14 , A61K49/04
CPC分类号： B82Y5/00 , A61K49/0428 , A61K9/146 , Y10S977/746 , Y10S977/881 , Y10S977/90 , Y10S977/915
摘要： This invention describes the preparation of nanoparticulate pharmaceutical agent dispersion via a process that comprises the dissolution of the said pharmaceutical agent in an alkaline solution and then neutralizing the said solution with an acid in the presence of suitable surface-modifying, surface-active agents to form a fine particle dispersion of the said pharmaceutical agent. A combination of surface active surface modifying agents comprising a nonionic surface active substance and an anionic surface active material having a chemical structure which is at least on a molecular basis 75% similar to the pharmaceutical agent is used. This process is preferably followed by steps of diafiltration clean-up of the dispersion and then concentration of it to a desired level. This process of dispersion preparation leads to microcrystalline particles of Z-average diameters smaller than 400 nm as measured by photon correlation spectroscopy. Various modifications of precipitation schemes are described, many of which are suitable for large-scale manufacture of these agent dispersions.
摘要翻译：本发明描述了纳米颗粒药剂分散体的制备方法，该方法包括将所述药剂溶解在碱性溶液中，然后在合适的表面改性表面活性剂存在下用酸中和所述溶液形成所述药剂的细颗粒分散体。使用包含非离子表面活性物质的表面活性表面改性剂和具有与药剂相似至少分子量为75％的化学结构的阴离子表面活性物质的组合。该方法优选的是通过渗滤清洁分散体的步骤，然后将其浓缩至期望的水平。这种分散制备过程导致通过光子相关光谱测量的Z平均直径小于400nm的微晶颗粒。描述了沉淀方案的各种改进，其中许多适用于这些试剂分散体的大规模生产。

2. 发明授权

US5662883A Microprecipitation of micro-nanoparticulate pharmaceutical agents 失效
标题翻译：微纳米颗粒药剂的微沉淀
公开(公告)号：US5662883A
公开(公告)日：1997-09-02
申请号：US370936
申请日：1995-01-10
申请人： Pranab Bagchi , Robert C. Stewart , Gregory L. McIntire , John R. Minter
发明人： Pranab Bagchi , Robert C. Stewart , Gregory L. McIntire , John R. Minter
IPC分类号： A61K9/14 , A61K49/04
CPC分类号： A61K49/0433 , A61K9/146 , Y10S977/775 , Y10S977/915 , Y10S977/927 , Y10S977/928
摘要： It has been known that administration of pharmaceutical agents (both diagnostic and therapeutic) with poor water solubility in the form of particles less than 400 nm in diameter produces agent formulation with increased bioavailibility. Bioavailability being proportional to the surface area, increases with reduction of particle size of the dispersed agent. We have discovered that chemical derivatization of certain photographic coupler molecules with chemical moiety that are capable of functioning as pharmaceutical agents (both diagnostic and therapeutic) is amenable to the preparation of nanoparticulate pharmaceutical agent dispersions via a process that comprises the dissolution of the said pharmaceutical agent in an alkaline solution and then neutralizing the said solution with an acid in the presence of a suitable surface-modifying, surface-active agent to form an ultra fine particle dispersion of the said pharmaceutical agent. The composition and process of this invention leads to particles of Z-average diameters as small as up to 10 nm as measured by photon correlation spectroscopy. The composition and process schemes of this invention are suitable for large-scale manufacture of these micro-nanoparticulate pharmaceutical agent dispersions.
摘要翻译：已经知道直径小于400nm的颗粒形式的水溶性差的药物（诊断和治疗）的给药产生具有增加的生物利用度的药剂制剂。与表面积成比例的生物利用度随着分散剂的粒度的降低而增加。我们已经发现，具有能够用作药剂（诊断和治疗）的具有化学部分的某些照相成色剂分子的化学衍生化适用于通过包括所述药剂的溶解的方法制备纳米颗粒药剂分散体在碱性溶液中，然后在合适的表面改性表面活性剂存在下用酸中和所述溶液，以形成所述药剂的超细颗粒分散体。本发明的组合物和方法通过光子相关光谱法测得的Z平均直径小至10nm的颗粒。本发明的组合物和方法适用于大规模制造这些微纳米颗粒药剂分散体。

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