公开(公告)号：US20140371712A1

公开(公告)日：2014-12-18

申请号：US14314119

申请日：2014-06-25

申请人： William L. Olbricht ,  Keith B. Neeves ,  Conor Foley ,  Russell T. Matthews ,  W. Mark Saltzman ,  Andrew Sawyer

发明人： William L. Olbricht ,  Keith B. Neeves ,  Conor Foley ,  Russell T. Matthews ,  W. Mark Saltzman ,  Andrew Sawyer

IPC分类号： A61K38/47 ,  A61M5/14 ,  A61M37/00

CPC分类号： A61K38/47 ,  A61M5/1408 ,  A61M37/00 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2210/0693 ,  C12Y302/01 ,  C12Y302/01035

摘要： An embodiment of the invention is directed to a microfabricated, silicon-based, Convection Enhanced Delivery (CED) device. The device comprises a silicon shank portion, at least one individual parylene channel disposed along at least a part of an entire length of the shank, wherein the channel has one or more dimensioned fluid exit ports disposed at one or more respective locations of the channel and a fluid (drug) input opening. The fluid input opening may be configured or adapted to be connected to a fluid reservoir and/or a pump and/or a meter and/or a valve or other suitable control device(s) or apparatus that supplies and/or delivers fluid (e.g., a drug) to the microfabricated device. The device may have multiple channels disposed side by side or in different surfaces of the device. The device may be rigid, or flexible, in which case a flexible device can be attached to a bio-degradable support scaffold that provides sufficient structural rigidity for insertion of the device into the target tissue. In certain “functionalized” embodiments of the invention, the CED device is equipped with integrated electrodes and/or a sensor (e.g., glutamate) to detect and convey selective parametric information. Another embodiment of the invention is directed to a CED method for drugs and/or other agents. The method may comprise the delivery of enzymes or other materials to modify tissue permeability and improve drug diffusion. Another embodiment of the invention is directed to a method for making a device for CED of drugs.

摘要翻译： 本发明的一个实施例涉及一种微加工的硅基对流增强递送（CED）装置。 所述装置包括硅柄部分，至少一个单独的聚对二甲苯通道沿着所述柄部的整个长度的至少一部分设置，其中所述通道具有设置在所述通道的一个或多个相应位置处的一个或多个尺寸尺寸的流体出口， 流体（药物）输入口。 流体输入开口可以被配置或适于连接到供给和/或输送流体的流体储存器和/或泵和/或流量计和/或阀或其它合适的控制装置或装置。 ，一种药物）到微细化装置。 该装置可以具有并排设置在装置的不同表面中的多个通道。 该装置可以是刚性的或柔性的，在这种情况下，柔性装置可以连接到生物可降解的支撑支架上，其提供足够的结构刚性以将装置插入到靶组织中。 在本发明的某些“功能化”实施例中，CED装置配备有集成电极和/或传感器（例如谷氨酸盐）以检测和传送选择性参数信息。 本发明的另一个实施方案涉及用于药物和/或其他试剂的CED方法。 该方法可以包括递送酶或其它材料以改变组织渗透性并改善药物扩散。 本发明的另一个实施方案涉及制备用于药物的CED的装置的方法。

公开(公告)号：US09844585B2

公开(公告)日：2017-12-19

申请号：US14314119

申请日：2014-06-25

申请人： William L. Olbricht ,  Keith B. Neeves ,  Conor Foley ,  Russell T. Matthews ,  W. Mark Saltzman ,  Andrew Sawyer

发明人： William L. Olbricht ,  Keith B. Neeves ,  Conor Foley ,  Russell T. Matthews ,  W. Mark Saltzman ,  Andrew Sawyer

IPC分类号： A61M37/00 ,  A61K38/47 ,  A61M5/14

CPC分类号： A61K38/47 ,  A61M5/1408 ,  A61M37/00 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2210/0693 ,  C12Y302/01 ,  C12Y302/01035

摘要： An embodiment of the invention is directed to a microfabricated, silicon-based, Convection Enhanced Delivery (CED) device. The device comprises a silicon shank portion, at least one individual parylene channel disposed along at least a part of an entire length of the shank, wherein the channel has one or more dimensioned fluid exit ports disposed at one or more respective locations of the channel and a fluid (drug) input opening. The fluid input opening may be configured or adapted to be connected to a fluid reservoir and/or a pump and/or a meter and/or a valve or other suitable control device(s) or apparatus that supplies and/or delivers fluid (e.g., a drug) to the microfabricated device. The device may have multiple channels disposed side by side or in different surfaces of the device. The device may be rigid, or flexible, in which case a flexible device can be attached to a bio-degradable support scaffold that provides sufficient structural rigidity for insertion of the device into the target tissue. In certain “functionalized” embodiments of the invention, the CED device is equipped with integrated electrodes and/or a sensor (e.g., glutamate) to detect and convey selective parametric information. Another embodiment of the invention is directed to a CED method for drugs and/or other agents. The method may comprise the delivery of enzymes or other materials to modify tissue permeability and improve drug diffusion. Another embodiment of the invention is directed to a method for making a device for CED of drugs.

公开(公告)号：US08790317B2

公开(公告)日：2014-07-29

申请号：US12525393

申请日：2008-02-12

申请人： William L. Olbricht ,  Keith B. Neeves ,  Conor Foley ,  Russell T. Mattews ,  W. Mark Saltzman ,  Andrew Sawyer

发明人： William L. Olbricht ,  Keith B. Neeves ,  Conor Foley ,  Russell T. Mattews ,  W. Mark Saltzman ,  Andrew Sawyer

IPC分类号： A61M5/00

CPC分类号： A61K38/47 ,  A61M5/1408 ,  A61M37/00 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2210/0693 ,  C12Y302/01 ,  C12Y302/01035

摘要： An embodiment of the invention is directed to a microfabricated, silicon-based, Convection Enhanced Delivery (CED) device. The device comprises a silicon shank portion, at least one individual parylene channel disposed along at least a part of an entire length of the shank, wherein the channel has one or more dimensioned fluid exit ports disposed at one or more respective locations of the channel and a fluid (drug) input opening. The fluid input opening may be configured or adapted to be connected to a fluid reservoir and/or a pump and/or a meter and/or a valve or other suitable control device(s) or apparatus that supplies and/or delivers fluid (eg, a drug) to the microfabricated device. The device may have multiple channels disposed side by side or in different surfaces of the device.

摘要翻译： 本发明的一个实施例涉及一种微加工的硅基对流增强递送（CED）装置。 所述装置包括硅柄部分，至少一个单独的聚对二甲苯通道沿着所述柄部的整个长度的至少一部分设置，其中所述通道具有设置在所述通道的一个或多个相应位置处的一个或多个尺寸尺寸的流体出口， 流体（药物）输入口。 流体输入开口可以被配置或适于连接到供给和/或输送流体的流体储存器和/或泵和/或流量计和/或阀或其它合适的控制装置或装置。 ，一种药物）到微细化装置。 该装置可以具有并排设置在装置的不同表面中的多个通道。

公开(公告)号：US06322815B1

公开(公告)日：2001-11-27

申请号：US08279302

申请日：1994-07-22

申请人： W. Mark Saltzman ,  O. Michael Colvin ,  Wenbin Dang ,  Susan Ludeman

发明人： W. Mark Saltzman ,  O. Michael Colvin ,  Wenbin Dang ,  Susan Ludeman

IPC分类号： A61K914

CPC分类号： A61K47/34 ,  A61K47/61

摘要： Polymeric drug conjugates in controlled release matrices are provided which allow sustained concentrations of therapeutic agents within a treated area for a prolonged period. The polymeric drug conjugates hydrolytically degrade in the extracellular space in a controlled, pre-specified pattern, releasing active drug. The conjugates diffuse within the tissue reaching a greater distance from the matrix than free drug would, because of their reduced rate of clearance from the tissue via the capillary system.

摘要翻译： 提供控制释放基质中的聚合物药物偶联物，其允许治疗区域内持续浓度的治疗剂长时间。 聚合物药物缀合物在受控的预先规定的模式中在细胞外空间中水解降解，释放活性药物。 由于它们通过毛细管系统从组织中的清除率降低，所以组合物在组织内扩散到与基质相比比自由药物更大的距离。

公开(公告)号：US09241898B2

公开(公告)日：2016-01-26

申请号：US12922023

申请日：2009-03-11

申请人： W. Mark Saltzman ,  Kim Woodrow

发明人： W. Mark Saltzman ,  Kim Woodrow

IPC分类号： C07H21/04 ,  C07H21/02 ,  A61K9/14 ,  A61K9/00 ,  A61K9/51 ,  C12N15/11 ,  C12N15/113

CPC分类号： A61K9/0034 ,  A61K9/0014 ,  A61K9/0036 ,  A61K9/5146 ,  A61K9/5153 ,  C12N15/111 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2320/32 ,  C12Y207/01037

摘要： Polymeric nanoparticles encapsulating inhibitory ribonucleic acids (RNAs) and methods of their manufacture and use are provided. Advantageous properties of the nanoparticles include: 1) high encapsulation efficiency of inhibitory RNAs into the nanoparticles, 2) small size of the nanoparticles that increases cell internalization, and 3) sustained release of encapsulated inhibitory RNAs by the nanoparticles that allows for administration of an effective amount of inhibitory RNAs to cells or tissues over extended periods of time. Encapsulation efficiency of inhibitory RNAs into the nanoparticles is greatly increased by complexing the inhibitory RNAs to polycations prior to encapsulation. Methods of using the polymeric nanoparticles for treating or inhibiting diseases or disorders are provided.

摘要翻译： 提供了包封抑制性核糖核酸（RNAs）的聚合物纳米颗粒及其制造和使用方法。 纳米颗粒的有利特性包括：1）抑制性RNA在纳米颗粒中的高封装效率，2）增加细胞内化的纳米粒子的小尺寸，以及3）允许施用有效的纳米颗粒的包封的抑制性RNA的持续释放 在长时间内对细胞或组织的抑制性RNA的量。 通过在封装之前将抑制性RNA与聚阳离子络合，大大增加了抑制性RNA进入纳米颗粒的封装效率。 提供了使用聚合物纳米颗粒治疗或抑制疾病或病症的方法。

公开(公告)号：US06319715B1

公开(公告)日：2001-11-20

申请号：US09556074

申请日：2000-04-21

申请人： Dan Luo ,  W. Mark Saltzman ,  Ernest Han ,  Nadya Belcheva

发明人： Dan Luo ,  W. Mark Saltzman ,  Ernest Han ,  Nadya Belcheva

IPC分类号： C12N1588

CPC分类号： C12N15/87 ,  Y10S977/906

摘要： The present invention provides a method for enhancing the delivery of nucleic acid molecules to cells by increasing the concentration of cells at the cell surface. The method comprises the step of premixing of nucleic acid:vector molecules with nanoparticles that are biocompatible, reversibly associate with the nucleic acids and have a sedimentation rate which increases the concentration of the nucleic acids at the cell surface so as to enhance delivery into the cells.

摘要翻译： 本发明提供了通过增加细胞表面细胞浓度来增强核酸分子向细胞递送的方法。 该方法包括以下步骤：将核酸：载体分子与生物相容的纳米颗粒预混合，与核酸可逆地结合并具有增加核酸在细胞表面的浓度的沉降速率，从而增强向细胞的传递 。