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    • 14. 发明申请
    • EMULSION-BASED PROCESSES FOR MAKING MICROPARTICLES
    • 基于乳液的微粒制备工艺
    • WO0066087A9
    • 2001-07-12
    • PCT/US0011781
    • 2000-05-02
    • SOUTHERN BIOSYSTEMS INCGIBSON JOHN WHOLL RICHARD JTIPTON ARTHUR J
    • GIBSON JOHN WHOLL RICHARD JTIPTON ARTHUR J
    • A61K9/16B01J13/12
    • B01J13/125A61K9/1647A61K9/1694Y10T428/2984Y10T428/2985
    • Processes for making microparticles, preferably containing an active agent, are provided. In a preferred embodiment, the process involves preparing (1) a dispersed phase containing an agent in a solution of polymer and a first solvent; (2) a continuous phase containing a surfactant, a second solvent that is totally or partially immiscible with the first solvent, and sufficient first solvent to saturate the continuous phase; and (3) an extraction phase that is a nonsolvent for the polymer, a solvent for the continuous phase components, and a solvent for the first solvent, wherein the first solvent has solubility in the extraction phase of between about 0,1 % and 25 % by weight. Then, the dispersed phase and the continuous phase are mixed to form an emulsion, and the emulsion is then briefly mixed with a suitable quantity of extraction phase to induce skin formation at the interface of the dispersed and continuous phases. Remaining solvent is removed by an evaporation process step. The emulsification and solvent removal steps are preferably conducted in a continuous process. The brief extraction step prior to evaporation minimizes the loss of active agent from the microparticles, and reduces the required volume of extraction phase as compared to other extraction-based processes. Alternate emulsification methods and solvent removal methods, such as incremental extraction, cryogenic extraction, or membrane separation, also are provided, and can be used in various combinations to make microparticles.
    • 提供了制造优选含有活性剂的微粒的方法。 在一个优选的实施方案中,该方法涉及制备(1)在聚合物和第一溶剂的溶液中含有试剂的分散相; (2)含有表面活性剂,与第一溶剂完全或部分不混溶的第二溶剂和足以使连续相饱和的第一溶剂的连续相; 和(3)作为聚合物的非溶剂的萃取相,连续相组分的溶剂和第一溶剂的溶剂,其中第一溶剂在萃取相中的溶解度为约0.1%至25% 重量%。 然后,将分散相和连续相混合形成乳液,然后将乳液与适量的萃取相短暂混合,以在分散相和连续相的界面处诱导皮肤形成。 剩余溶剂通过蒸发工艺步骤除去。 乳化和溶剂去除步骤优选以连续方法进行。 与其他基于提取的方法相比,在蒸发之前的简单提取步骤使来自微粒的活性剂的损失最小化,并且减少了所需的提取相体积。 还提供了替代乳化方法和溶剂去除方法,如增量提取,深冷提取或膜分离,并且可以以各种组合使用以制造微粒。
    • 16. 发明申请
    • POLYMERIC IMPLANTS, PREFERABLY CONTAINING A MIXTURE OF PEG AND PLG, FOR CONTROLLED RELEASE OF ACTIVE AGENTS, PREFERABLY A GNRH
    • 聚合物植入物,优选含有PEG和PLG的混合物,用于控制释放活性剂,优选A GNRH
    • WO2005067889A1
    • 2005-07-28
    • PCT/US2004/043389
    • 2004-12-23
    • DURECT CORPORATIONGIBSON, John, W.TIPTON, Arthur, J.
    • GIBSON, John, W.TIPTON, Arthur, J.
    • A61K9/00
    • A61K47/34A61K9/0024A61K9/1635A61K9/1647A61K9/2031A61K38/09A61K38/24
    • Polymeric devices for controlled release of an active agent of interest are provided. The active agent is provided within a biodegradable polymer system to supply a polymeric device for controlled release of the active agent. The polymer system is a copolymer or a polymer blend comprising a hydrophobic component and a hydrophilic component, and the polymer system does not form a hydrogel when contacted with, or immersed in an aqueous system, for example when the device is implanted in a subject. When the device is administered to a subject, for example, when it is implanted, the device releases the active agent in a controlled fashion without a lag period, or with a minimal lag period. Methods for producing the polymeric devices are also provided, as are methods of using the polymeric devices to provide for controlled release of an active agent in a subject. Preferred hydrophobic component is a PLG. Preferred hydrophilic Components are a PEG or a methoxyPEG. Preferred peptides are LHRH, goserelin, leuprolide.
    • 提供了用于感兴趣的活性剂的控制释放的聚合装置。 活性剂提供在可生物降解的聚合物体系内,以提供用于活性剂的受控释放的聚合物装置。 聚合物体系是包含疏水组分和亲水组分的共聚物或聚合物共混物,并且聚合物体系当与例如当将该装置植入受试者中时与水系统接触或浸没在水系统中时不形成水凝胶。 当将装置施用于受试者时,例如,当其被植入时,该装置以受控的方式释放活性剂,而没有滞后期或具有最小滞后期。 还提供了生产聚合物装置的方法,以及使用聚合物装置来提供受试者中活性剂的受控释放的方法。 优选的疏水组分是PLG。 优选的亲水组分是PEG或甲氧基PEG。 优选的肽是LHRH,戈舍瑞林,亮丙瑞林。