公开(公告)号：US06283953B1

公开(公告)日：2001-09-04

申请号：US09217822

申请日：1998-12-22

申请人： Rupal Ayer ,  James B. Eckenhoff ,  Stephen A. Berry ,  Gregory R. Stewart ,  Scott D. Jordan

发明人： Rupal Ayer ,  James B. Eckenhoff ,  Stephen A. Berry ,  Gregory R. Stewart ,  Scott D. Jordan

IPC分类号： A61K922

CPC分类号： A61K9/0004 ,  A61K9/0024 ,  A61M5/1424 ,  A61M5/1684 ,  A61M25/0108 ,  A61M31/002 ,  A61M2250/00

摘要： Performance of delivery systems for delivering beneficial agents to an animal are monitored to determine the delivery rate of the beneficial agent and the proper operation of the beneficial agent delivery device. Performance monitoring can be achieved by monitoring the physical configuration of the implanted osmotic delivery device from the exterior of the body to determine the amount of beneficial agent delivered and/or the delivery rate of the beneficial agent. The monitoring of the physical configuration of the implanted osmotic delivery device may be performed in different manners such as by X-ray or fluoroscopic monitoring of the implant structure or magnetic determination of a piston location within the implant. Performance monitoring can also be achieved by use of a performance marker within the beneficial agent to produce a specifically detectable response which can be measured noninvasively in body fluids or by-products.

摘要翻译： 监测用于向动物递送有益试剂的递送系统的性能以确定有益试剂的递送速率和有益试剂递送装置的适当操作。 可以通过从身体外部监测植入的渗透输送装置的物理构型来确定递送的有益药物的量和/或有益药物的递送速率来实现性能监测。 植入的渗透输送装置的物理结构的监测可以以不同的方式进行，例如通过X射线或荧光透视监测植入物结构或磁性确定植入物内的活塞位置。 还可以通过使用有益试剂中的性能标记来产生可在体液或副产物中非侵入性地测量的特异性可检测的反应来实现性能监测。

公开(公告)号：US06287295B1

公开(公告)日：2001-09-11

申请号：US09121878

申请日：1998-07-24

申请人： Guohua Chen ,  Scott D. Lautenbach ,  Keith E. Dionne ,  Scott D. Jordan ,  Steve A. Berry ,  Craig I. Rodenberger ,  Rupal Ayer

发明人： Guohua Chen ,  Scott D. Lautenbach ,  Keith E. Dionne ,  Scott D. Jordan ,  Steve A. Berry ,  Craig I. Rodenberger ,  Rupal Ayer

IPC分类号： A61K922

CPC分类号： A61K9/0004

摘要： Osmotic delivery system semipermeable body assemblies that control the delivery rate of a beneficial agent from an osmotic delivery system incorporating one of the semipermeable body assemblies. A semipermeable body assembly or plug includes a semipermeable body which is positionable in an opening of an osmotic delivery system. The semipermeable body has a hollow interior portion having a size selected to obtain a predetermined liquid permeation rate through the semipermeable body. Because the beneficial agent in the osmotic delivery system is delivered at substantially the same rate the osmotic agent imbibes liquid which has permeated through the plug from a surrounding environment, the liquid permeation rate through the plug controls the delivery rate of the beneficial agent from the osmotic delivery system. The liquid permeation rate through a semipermeable body may be varied to control the delivery rate of beneficial agent from an osmotic delivery system by changing the thickness of the semipermeable body or by changing an amount of surface area of the semipermeable body that is exposed to liquid when the osmotic delivery system is located in a liquid environment of use.

摘要翻译： 渗透输送系统半透性体组件，其从包含半透性体组件的渗透输送系统中控制有益剂的输送速率。 半透性体组件或塞子包括半渗透体，其可定位在渗透递送系统的开口中。 半透明体具有中空的内部部分，其具有选择的尺寸以获得通过半透性体的预定液体渗透速率。 由于渗透输送系统中的有益剂以基本上相同的速率递送，所以渗透剂吸收从周围环境渗透通过塞子的液体，通过塞子的液体渗透速率控制有益剂从渗透压的输送速率 输送系统。 可以改变通过半透性体的液体渗透速率，以通过改变半透性体的厚度或通过改变暴露于液体的半透明体的表面积的量来控制有益剂从渗透递送系统的输送速率， 渗透输送系统位于使用的液体环境中。

公开(公告)号：US06923800B2

公开(公告)日：2005-08-02

申请号：US09859428

申请日：2001-05-18

申请人： Guohua Chen ,  Scott D. Lautenbach ,  Keith E. Dionne ,  Scott D. Jordan ,  Steve A. Berry ,  Craig I. Rodenberger ,  Rupal Ayer

发明人： Guohua Chen ,  Scott D. Lautenbach ,  Keith E. Dionne ,  Scott D. Jordan ,  Steve A. Berry ,  Craig I. Rodenberger ,  Rupal Ayer

IPC分类号： A61K9/00 ,  A61K9/22 ,  A61K9/24 ,  A61K9/52

CPC分类号： A61K9/0004

摘要： Osmotic delivery system semipermeable body assemblies that control the delivery rate of a beneficial agent from an osmotic delivery system incorporating one of the semipermeable body assemblies are provided. A semipermeable body assembly or plug includes a semipermeable body which is positionable in an opening of an osmotic delivery system. The semipermeable body has a hollow interior portion having a size selected to obtain a predetermined liquid permeation rate through the semipermeable body. Because the beneficial agent in the osmotic delivery system is delivered at substantially the same rate, the osmotic agent imbibes liquid which has permeated through the plug from a surrounding environment, and the liquid permeation rate through the plug controls the delivery rate of the beneficial agent from the osmotic delivery system. The liquid permeation rate through a semipermeable body may be varied to control the delivery rate of beneficial agent from an osmotic delivery system by changing the thickness of the semipermeable body or by changing an amount of surface area of the semipermeable body that is exposed to liquid when the osmotic delivery system is located in a liquid environment of use.

公开(公告)号：US20050107772A1

公开(公告)日：2005-05-19

申请号：US10953895

申请日：2004-09-29

申请人： Guohua Chen ,  Rupal Ayer ,  Scott Lautenbach

发明人： Guohua Chen ,  Rupal Ayer ,  Scott Lautenbach

IPC分类号： A61K9/00 ,  A61K9/22 ,  A61M5/145

CPC分类号： A61K9/0024 ,  A61K9/0004 ,  A61M5/145 ,  A61M2005/14513

摘要： In one aspect, the present invention is directed to an osmotic pump that automatically provides an ascending release rate of active agent as the osmotic pump functions in an environment of operation and may be designed for implantation within a desired animal or human subject. An osmotic pump according to the present invention includes a reservoir, a rate controlling membrane, an expandable osmotic composition, an active agent formulation and an exit orifice. Once administered to an environment of operation, water passes through the rate controlling membrane and into the osmotic composition, which causes the osmotic composition to expand and expel the active agent formulation through the exit orifice at a rate that is directly proportional to the rate at which water passes through the rate controlling membrane. An osmotic pump according to the present invention permits the flow of water through the rate controlling membrane to increase automatically without the need for manipulation of the osmotic pump after administration. As the flow of water through the rate controlling membrane increases, the rate at which active agent is delivered from the osmotic pump will also increase proportionally.

摘要翻译： 一方面，本发明涉及一种渗透泵，其随着渗透泵在操作环境中的功能而自动提供活性剂的上升释放速率，并且可被设计用于植入期望的动物或人类受试者内。 根据本发明的渗透泵包括储存器，速率控制膜，可膨胀渗透组合物，活性剂制剂和出口孔。 一旦施用于操作环境，水通过速率控制膜并进入渗透组合物，其导致渗透组合物通过出口孔膨胀并排出活性剂制剂，速率与其速率成正比 水通过速率控制膜。 根据本发明的渗透泵允许通过速率控制膜的水流自动增加，而不需要在给药后操纵渗透泵。 随着通过速率控制膜的水流量增加，活性剂从渗透泵输送的速率也将成比例地增加。

公开(公告)号：US06270787B1

公开(公告)日：2001-08-07

申请号：US09217823

申请日：1998-12-22

申请人： Rupal Ayer

发明人： Rupal Ayer

IPC分类号： A61K952

CPC分类号： A61K9/0004

摘要： An osmotic delivery system has a membrane plug retention mechanism which can also be used to control the delivery rate of a beneficial agent from the osmotic delivery system. The osmotic delivery device includes an implant capsule containing a beneficial agent and an osmotic agent. Holes are formed along a side wall of the implant capsule at an open end of the capsule. When the membrane plug is inserted into the open end of the capsule the membrane material swells into the holes in the capsule side wall creating a large frictional force which prevents expulsion of the membrane plug. A beneficial agent delivery rate of the osmotic delivery system is controllable by varying the size and number of the holes to change the amount of exposed surface area of the membrane plug. An increase in the surface area of the membrane plug exposed to the exterior environment causes a corresponding increase in the liquid permeation rate of the membrane and thus, increases the beneficial agent delivery rate.

公开(公告)号：US20060263433A1

公开(公告)日：2006-11-23

申请号：US11347109

申请日：2006-02-03

申请人： Rupal Ayer ,  Paula Dennis ,  Michael Desjardin ,  Stan Lam ,  Kui Liu ,  James Matsuura ,  Latha Narayanan ,  Catherine Rohloff ,  Pauline Zamora

发明人： Rupal Ayer ,  Paula Dennis ,  Michael Desjardin ,  Stan Lam ,  Kui Liu ,  James Matsuura ,  Latha Narayanan ,  Catherine Rohloff ,  Pauline Zamora

IPC分类号： A61K38/21 ,  A61K9/14

CPC分类号： A61K38/21 ,  A61F2250/0068 ,  A61K9/0004 ,  A61K9/0019 ,  A61K9/0024 ,  A61K9/10 ,  A61K9/1617 ,  A61K9/1623 ,  A61K9/1694 ,  A61K9/19

摘要： A suspension formulation of interferon includes a non-aqueous, single-phase vehicle including at least one polymer and at least one solvent, the vehicle exhibiting viscous fluid characteristics, and an interferon contained in a particle formulation dispersed in the vehicle. The particle formulation includes a stabilizing component comprising one or more stabilizers selected from the group consisting of carbohydrates, antioxidants, and amino acids. The suspension formulation is characterized in that less than 10% of the interferon degrades over 3 months under an accelerated storage condition.

摘要翻译： 干扰素的悬浮液制剂包括非水性单相载体，其包含至少一种聚合物和至少一种溶剂，所述载体表现出粘性流体特性，以及包含在分散在载体中的颗粒制剂中的干扰素。 颗粒制剂包括稳定组分，其包含一种或多种选自碳水化合物，抗氧化剂和氨基酸的稳定剂。 悬浮液制剂的特征在于，在加速储存条件下，少于10％的干扰素在3个月内降解。

公开(公告)号：US20060193918A1

公开(公告)日：2006-08-31

申请号：US11347562

申请日：2006-02-03

申请人： Catherine Rohloff ,  Guohua Chen ,  Andrew Luk ,  Rupal Ayer ,  Paul Houston ,  Michael Desjardin ,  Pauline Zamora ,  Stan Lam

发明人： Catherine Rohloff ,  Guohua Chen ,  Andrew Luk ,  Rupal Ayer ,  Paul Houston ,  Michael Desjardin ,  Pauline Zamora ,  Stan Lam

IPC分类号： A61K38/19 ,  A61K38/22 ,  A61K38/48 ,  A61K9/14

CPC分类号： A61K38/21 ,  A61K9/0004 ,  A61K9/0024 ,  A61K9/10 ,  A61K38/043 ,  A61K38/085 ,  A61K38/09 ,  A61K38/105 ,  A61K38/11 ,  A61K38/1808 ,  A61K38/185 ,  A61K38/191 ,  A61K38/2242 ,  A61K38/225 ,  A61K38/24 ,  A61K38/26 ,  A61K38/27 ,  A61K38/28 ,  A61K38/31 ,  A61K38/35 ,  A61K38/36 ,  A61K47/02 ,  A61K47/10 ,  A61K47/12 ,  A61K47/14 ,  A61K47/20 ,  A61K47/26 ,  A61K47/32 ,  Y10T29/494 ,  Y10T29/49826

摘要： A nonaqueous, single-phase vehicle that is capable of suspending an active agent. The nonaqueous, single-phase vehicle includes at least one solvent and at least one polymer and is formulated to exhibit phase separation upon contact with an aqueous environment. The at least one solvent may be selected from the group consisting of benzyl benzoate, decanol, ethyl hexyl lactate, and mixtures thereof and the at least one polymer may be selected from the group consisting of a polyester, pyrrolidone, ester of an unsaturated alcohol, ether of an unsaturated alcohol, polyoxyethylenepolyoxypropylene block copolymer, and mixtures thereof. In one embodiment, the at least one solvent is benzyl benzoate and the at least one polymer is polyvinylpyrrolidone. A stable, nonaqueous suspension formulation that includes the nonaqueous, single-phase vehicle and an active agent, and a method of forming the same, are also disclosed.

公开(公告)号：US06899887B2

公开(公告)日：2005-05-31

申请号：US09858632

申请日：2001-05-17

申请人： Rupal Ayer

发明人： Rupal Ayer

IPC分类号： A61M37/00 ,  A61K9/00 ,  A61K9/22 ,  A61K9/52 ,  A61F2/02

CPC分类号： A61K9/0004

摘要： An osmotic delivery system has a membrane plug retention mechanism which can also be used to control the delivery rate of a beneficial agent from the osmotic delivery system. The osmotic delivery device includes an implant capsule containing a beneficial agent and an osmotic agent. Holes are formed along a side wall of the implant capsule at an open end of the capsule. When the membrane plug is inserted into the open end of the capsule, the membrane material swells into the holes in the capsule side wall creating a large frictional force which prevents expulsion of the membrane plug. A beneficial agent delivery rate of the osmotic delivery system is controllable by varying the size and number of the holes to change the amount of exposed surface area of the membrane plug. An increase in the surface area of the membrane plug exposed to the exterior environment causes a corresponding increase in the liquid permeation rate of the membrane and thus, increases the beneficial agent delivery rate.

公开(公告)号：US20050281877A1

公开(公告)日：2005-12-22

申请号：US11196758

申请日：2005-08-02

申请人： Guohua Chen ,  Scott Lautenbach ,  Keith Dionne ,  Scott Jordan ,  Steve Berry ,  Craig Rodenberger ,  Rupal Ayer

发明人： Guohua Chen ,  Scott Lautenbach ,  Keith Dionne ,  Scott Jordan ,  Steve Berry ,  Craig Rodenberger ,  Rupal Ayer

IPC分类号： A61K9/00 ,  A61K9/22 ,  A61K9/24 ,  A61K9/52

CPC分类号： A61K9/0004

摘要： Osmotic delivery system semipermeable body assemblies that control the delivery rate of a beneficial agent from an osmotic delivery system incorporating one of the semipermeable body assemblies are provided. A semipermeable body assembly or plug includes a semipermeable body which is positionable in an opening of an osmotic delivery system. The semipermeable body has a hollow interior portion having a size selected to obtain a predetermined liquid permeation rate through the semipermeable body. Because the beneficial agent in the osmotic delivery system is delivered at substantially the same rate, the osmotic agent imbibes liquid which has permeated through the plug from a surrounding environment, and the liquid permeation rate through the plug controls the delivery rate of the beneficial agent from the osmotic delivery system. The liquid permeation rate through a semipermeable body may be varied to control the delivery rate of beneficial agent from an osmotic delivery system by changing the thickness of the semipermeable body or by changing an amount of surface area of the semipermeable body that is exposed to liquid when the osmotic delivery system is located in a liquid environment of use.

摘要翻译： 提供了渗透输送系统半透性体组件，其从包含半透性体组件的渗透输送系统控制有益剂的输送速率。 半透性体组件或塞子包括半渗透体，其可定位在渗透递送系统的开口中。 半透明体具有中空的内部部分，其具有选择的尺寸以获得通过半透性体的预定液体渗透速率。 由于渗透输送系统中的有益剂以基本上相同的速率递送，所以渗透剂吸收从周围环境透过塞子的液体，并且通过塞子的液体渗透速率控制有益剂的输送速率 渗透输送系统。 可以改变通过半透性体的液体渗透速率，以通过改变半透性体的厚度或通过改变暴露于液体的半透明体的表面积的量来控制有益剂从渗透递送系统的输送速率， 渗透输送系统位于使用的液体环境中。

公开(公告)号：US06976981B2

公开(公告)日：2005-12-20

申请号：US09858631

申请日：2001-05-17

申请人： Rupal Ayer

发明人： Rupal Ayer

IPC分类号： A61M37/00 ,  A61K9/00 ,  A61K9/22 ,  A61K9/52 ,  A61F2/02

CPC分类号： A61K9/0004

摘要： An osmotic delivery system has a membrane plug retention mechanism which can also be used to control the delivery rate of a beneficial agent from the osmotic delivery system. The osmotic delivery device includes an implant capsule containing a beneficial agent and an osmotic agent. Holes are formed along a side wall of the implant capsule at an open end of the capsule. When the membrane plug is inserted into the open end of the capsule, the membrane material swells into the holes in the capsule side wall creating a large frictional force which prevents expulsion of the membrane plug. A beneficial agent delivery rate of the osmotic delivery system is controllable by varying the size and number of the holes to change the amount of exposed surface area of the membrane plug. An increase in the surface area of the membrane plug exposed to the exterior environment causes a corresponding increase in the liquid permeation rate of the membrane and thus, increases the beneficial agent delivery rate.

摘要翻译： 渗透递送系统具有膜塞保持机构，其也可用于控制来自渗透递送系统的有益剂的递送速率。 渗透递送装置包括含有有益剂和渗透剂的植入物胶囊。 在胶囊的开口端沿着植入物胶囊的侧壁形成孔。 当膜塞插入胶囊的开口端时，膜材料膨胀到胶囊侧壁的孔中，产生大的摩擦力，防止膜塞的排出。 通过改变孔的尺寸和数量来改变膜塞的暴露表面积的量，可控制渗透递送系统的有益剂递送速率。 暴露于外部环境的膜塞的表面积的增加导致膜的液体渗透速率的相应增加，从而增加了有益剂的输送速率。