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    METHODS FOR STABILIZING BIOLOGICALLY ACTIVE AGENTS ENCAPSULATED IN BIODEGRADABLE CONTROLLED-RELEASE POLYMERS
    1.
    发明申请
    METHODS FOR STABILIZING BIOLOGICALLY ACTIVE AGENTS ENCAPSULATED IN BIODEGRADABLE CONTROLLED-RELEASE POLYMERS 审中-公开
    用于稳定可生物降解控制释放聚合物中生物活性剂的方法

    公开(公告)号：US20080182909A1

    公开(公告)日：2008-07-31

    申请号：US11863088

    申请日：2007-09-27

    申请人： Steven P. Schwendeman ,  Gaozhong Zhu ,  Hanne Bentz ,  Jeffrey A. Hubbell ,  Wenlei Jiang ,  Anna Shenderova ,  Jichao Kang

    发明人： Steven P. Schwendeman ,  Gaozhong Zhu ,  Hanne Bentz ,  Jeffrey A. Hubbell ,  Wenlei Jiang ,  Anna Shenderova ,  Jichao Kang

    IPC分类号： A61K47/30

    CPC分类号： A61K9/1647 ,  A61K9/0019 ,  A61K47/02

    摘要： Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.

    摘要翻译： 提供了用于减少或抑制在可生物降解的聚合物递送系统中的水溶性生物活性剂的不可逆失活的方法，其被设计为在长时间内释放这些试剂，例如PLGA递送系统。 该方法包括制备PLGA递送系统，其微生物即活性剂所在的孔在生物降解过程中均匀或均匀地保持3至9之间，优选4至8，更优选5至7.5之间的pH。 根据输送系统的尺寸和聚合物的初始体积渗透性，该结果通过（a）将水溶性载体引入输送系统来实现，（b）将选择的碱性添加剂（或抗酸剂）掺入 递送系统，（c）将水溶性载体和选择性碱性添加剂并入输送系统中，（d）添加成孔分子，以将低分子量单体和低聚物的释放速率提高到递送系统中（ e）使用具有降低的乙交酯含量的PLGA聚合物，即具有100％至75％丙交酯和0至25％乙交酯的PLGA）（f）使用产生更广泛孔隙网络的微胶囊化方法，例如 油包水乳液 - 溶剂萃取相对于水包油型水溶剂蒸发法，和（g）它们的组合。

    Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers
    2.
    发明授权
    Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers 失效
    用于稳定包封在可生物降解的控释聚合物中的生物活性剂的方法

    公开(公告)号：US06743446B2

    公开(公告)日：2004-06-01

    申请号：US09738961

    申请日：2000-12-15

    申请人： Steven P. Schwendeman ,  Gaozhong Zhu ,  Hanne Bentz ,  Jeffrey A. Hubbell ,  Wenlei Jiang ,  Anna Shenderova ,  Jichao Kang

    发明人： Steven P. Schwendeman ,  Gaozhong Zhu ,  Hanne Bentz ,  Jeffrey A. Hubbell ,  Wenlei Jiang ,  Anna Shenderova ,  Jichao Kang

    IPC分类号： A61K914

    CPC分类号： A61K9/1647 ,  A61K9/0019 ,  A61K47/02

    摘要： Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing a PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.

    摘要翻译： 提供了用于减少或抑制在可生物降解的聚合物递送系统中的水溶性生物活性剂的不可逆失活的方法，其被设计为在长时间内释放这些试剂，例如PLGA递送系统。 该方法包括制备PLGA递送系统，其微生物即活性剂所在的孔在生物降解过程中均匀或均匀地保持在3至9之间，优选4至8之间，更优选5至7.5的pH。 根据输送系统的尺寸和聚合物的初始体积渗透性，该结果通过（a）将水溶性载体引入输送系统来实现，（b）将选择的碱性添加剂（或抗酸剂）掺入 递送系统，（c）将水溶性载体和选择性碱性添加剂并入输送系统中，（d）添加成孔分子，以将低分子量单体和低聚物的释放速率提高到递送系统中（ e）使用具有降低的乙交酯含量的PLGA聚合物，即具有100％至75％丙交酯和0至25％乙交酯的PLGA）（f）使用产生更广泛孔隙网络的微胶囊化方法，例如 油包水乳液 - 溶剂萃取相对于水包油型水溶剂蒸发法，和（g）它们的组合。