公开(公告)号：US08440220B2

公开(公告)日：2013-05-14

申请号：US10420428

申请日：2003-04-22

申请人： Robert M. Gale ,  Thomas M. Stein ,  Jay Audett ,  Jane Stepic ,  Joseph B. Phipps ,  Michel J. N. Cormier

发明人： Robert M. Gale ,  Thomas M. Stein ,  Jay Audett ,  Jane Stepic ,  Joseph B. Phipps ,  Michel J. N. Cormier

IPC分类号： A61K9/70

CPC分类号： A61K9/7092 ,  A61K9/7061 ,  A61K31/4468 ,  A61K31/4535 ,  A61K45/06 ,  A61K2300/00

摘要： A transdermal analgesic system having reduced potential for abuse, wherein the system provides for the controlled release of the antagonist at a rate sufficient to provide an abuse limiting release rate ratio of the antagonist to the analgesic when the dosage form is subject to abuse is disclosed.

摘要翻译： 一种具有降低的滥用可能性的透皮镇痛系统，其中所述系统以足以在剂型受到滥用时提供拮抗剂与镇痛剂的滥用限制释放速率比的速率提供拮抗剂的受控释放。

公开(公告)号：US5624415A

公开(公告)日：1997-04-29

申请号：US427336

申请日：1995-04-24

申请人： Michel J. N. Cormier ,  Philip W. Ledger ,  Juanita Johnson ,  Joseph B. Phipps ,  Stella Chao

发明人： Michel J. N. Cormier ,  Philip W. Ledger ,  Juanita Johnson ,  Joseph B. Phipps ,  Stella Chao

IPC分类号： A61N1/30

CPC分类号： A61N1/0432 ,  A61N1/0448 ,  A61N1/0436

摘要： An electrotransport delivery device utilizing reservoir buffering at a select pH ranges in order to reduce skin irritation and skin resistance is provided. Cathodic reservoirs are buffered to a pH of less than about 4, preferably to a pH in the range of about 2 to 4, while anodic reservoirs are buffered to a pH above about 4, preferably to a pH in the range of about 4 to 10. Another electrotransport delivery device utilizes a potassium sensor to monitor potassium efflux from the skin. Potassium efflux above a certain predetermined level has been found to be a precursor to skin irritation/erythema. Operation of the device is modified (eg, terminated) when the predetermined potassium efflux level is sensed.

摘要翻译： 提供了一种在选择的pH范围内利用储存器缓冲以便减少皮肤刺激和皮肤抵抗的电输送输送装置。 阴极储存器缓冲至小于约4的pH，优选至约2至4范围内的pH，而阳极储存器缓冲至高于约4，优选至约4至10范围内的pH 另一种电输送装置利用钾传感器来监测来自皮肤的钾流出。 已经发现高于某一预定水平的钾流出物是皮肤刺激/红斑的前体。 当检测到预定的钾流出水平时，装置的操作被修改（例如，终止）。

公开(公告)号：US20090264855A1

公开(公告)日：2009-10-22

申请号：US12194984

申请日：2008-08-20

申请人： Joseph B. Phipps

发明人： Joseph B. Phipps

IPC分类号： A61N1/30

CPC分类号： A61N1/0448

摘要： The invention provides an improved electrotransport drug delivery system for analgesic drugs, namely fentanyl and sufentanil. The fentanyl/sufentanil is provided as a water soluble salt (eg, fentanyl hydrochloride) dispersed in a hydrogel formulation for use in an electrotransport device (10). In accordance with one aspect of the invention, the concentration of fentanyl/sufentanil in the donor reservoir (26) solution is above a predetermined minimum concentration, whereby the transdermal electrotransport flux of fentanyl/sufentanil is maintained independent of the concentration of fentanyl/sufentanil in solution. In accordance with a second aspect of the present invention, the donor reservoir (26) of the electrotransport delivery device (10) is comprised of silver and the donor reservoir (26) contains a predetermined “excess” loading of fentanyl/sufentanil halide to prevent silver ion migration with attendant skin discoloration. In accordance with a third aspect of the present invention, a transdermal electrotransport delivered dose of fentanyl/sufentanil is provided which is sufficient to induce analgesia in (eg, adult) human patients suffering from moderate-to-severe pain associated with major surgical procedures.

摘要翻译： 本发明提供了一种用于镇痛药物，即芬太尼和舒芬太尼的改进的电转运药物递送系统。 芬太尼/舒芬太尼作为分散在用于电转运装置（10）的水凝胶制剂中的水溶性盐（例如盐酸芬太尼）提供。 根据本发明的一个方面，供体储存器（26）溶液中芬太尼/舒芬太尼的浓度高于预定的最小浓度，由此芬太尼/舒芬太尼的透皮电转运通量与芬太尼/舒芬太尼的浓度无关 解。 根据本发明的第二方面，电运输输送装置（10）的供体储存器（26）由银组成，供体储存器（26）含有预定的“过量”负荷的芬太尼/舒芬太尼卤化物以防止 银离子迁移伴随皮肤变色。 根据本发明的第三方面，提供透皮电转运量的芬太尼/舒芬太尼，其足以在与主要外科手术相关的中度至重度疼痛的（例如成人）人类患者中诱发镇痛。

公开(公告)号：US06975902B2

公开(公告)日：2005-12-13

申请号：US10609211

申请日：2003-06-27

申请人： Joseph B. Phipps ,  Gary A. Lattin ,  Larry A. McNichols ,  John D. Badzinski

发明人： Joseph B. Phipps ,  Gary A. Lattin ,  Larry A. McNichols ,  John D. Badzinski

IPC分类号： A61N1/30

CPC分类号： A61N1/0448 ,  A61N1/044

摘要： A reservoir and a family of reservoirs are provided which are designed to be used with a single controller to provide a wide range of therapeutic drug delivering regimens while maintaining many of the same reservoir configurations and drug formulations. A method of making a reservoir and a family of reservoirs and incorporating them into an electrotransport system is disclosed.

摘要翻译： 提供了储存器和一系列储存器，其设计成与单个控制器一起使用以提供广泛的治疗药物递送方案，同时保持许多相同的储存器构型和药物制剂。 公开了一种制造储存器和一系列储存器并将其并入到电输送系统中的方法。

公开(公告)号：US06881208B1

公开(公告)日：2005-04-19

申请号：US08465492

申请日：1995-06-05

申请人： Joseph B. Phipps ,  Mary Southam ,  Keith J. Bernstein ,  Henk Noorduin

发明人： Joseph B. Phipps ,  Mary Southam ,  Keith J. Bernstein ,  Henk Noorduin

IPC分类号： A61K9/00 ,  A61K31/4468 ,  A61K31/4535 ,  A61N1/30 ,  A61P25/04 ,  A61M5/32

CPC分类号： A61N1/0436 ,  A61N1/0448

摘要： The invention provides an improved electrotransport drug delivery system for analgesic drugs, namely fentanyl and sufentanil. The fentanyl/sufentanil is provided as a water soluble salt (eg, fentanyl hydrochloride) dispersed in a hydrogel formulation for use in an electrotransport device (10). In accordance with one aspect of the invention, the concentration of fentanyl/sufentanil in the donor reservoir (26) solution is above a predetermined minimum concentration, whereby the transdermal electrotransport flux of fentanyl/sufentanil is maintained independent of the concentration of fentanyl/sufentanil in solution. In accordance with a second aspect of the present invention, the donor reservoir (26) of the electrotransport delivery device (10) is comprised of silver and the donor reservoir (26) contains a predetermined “excess” loading of fentanyl/sufentanil halide to prevent silver ion migration with attendant skin discoloration. In accordance with a third aspect of the present invention, a transdermal electrotransport delivered dose of fentanyl/sufentanil is provided which is sufficient to induce analgesia in (eg, adult) human patients suffering from moderate-to-severe pain associated with major surgical procedures.

公开(公告)号：US5711761A

公开(公告)日：1998-01-27

申请号：US394075

申请日：1995-02-24

申请人： Darrel F. Untereker ,  Joseph B. Phipps ,  Gary A. Lattin

发明人： Darrel F. Untereker ,  Joseph B. Phipps ,  Gary A. Lattin

IPC分类号： A61N1/30

CPC分类号： A61N1/30 ,  A61N1/0448 ,  A61N1/0436 ,  A61N1/044 ,  A61N1/0444

摘要： Improved methods of ionophoretic drug delivery are described. By the intentional selection of drug(s) with specific characteristics, of ionotophoresis device, components or both permits the efficiency of drug delivery is increased.

公开(公告)号：US4744787A

公开(公告)日：1988-05-17

申请号：US665698

申请日：1984-10-29

申请人： Joseph B. Phipps ,  Darrel F. Untereker

发明人： Joseph B. Phipps ,  Darrel F. Untereker

IPC分类号： A61N1/30 ,  A61N1/00

CPC分类号： A61N1/0448 ,  A61N1/0436 ,  A61N1/0444

摘要： Improved iontophoresis drug delivery apparatus or device wherein one or more electrochemically active components are employed or "sacrificed" so as to minimize the hydrolysis of water during drug delivery. Efficiency of drug delivery is increased and pH changes in the device or adjacent the patient's skin are minimized.

摘要翻译： 改进的离子电渗药物递送装置或装置，其中使用一种或多种电化学活性成分或“牺牲”，以使药物递送期间水的水解最小化。 药物递送的效率增加，并且装置中或患者皮肤附近的pH变化最小化。

公开(公告)号：US5591124A

公开(公告)日：1997-01-07

申请号：US452403

申请日：1995-05-26

申请人： Joseph B. Phipps

发明人： Joseph B. Phipps

IPC分类号： A61N1/30

CPC分类号： A61N1/044 ,  A61N1/0448 ,  A61N1/0436 ,  A61N1/0444

摘要： Methods for conducting controlled environment electrotransport are described. The methods generally concern control of the ionic environment of the active electrode reservoir, in an electrotransport system. This control may be utilized, for example, to maintain a constant extraneous ion presence, such as pH. It may also be applied in a preferred manner to maintain selected control over the delivery rate of a target species, in time, in the presence of extraneous ions. Apparatus usable to provide for controlled environment electrotransport are also described. In general the apparatus comprises an electrotransport system including an active electrode reservoir having therein both a primary electrode arrangement and a secondary electrode arrangement, with a control arrangement for selected operation of both. The secondary electrode arrangement, being operated different from the primary electrode arrangement, is selected for operation to selectively enhance or otherwise modify ion presence in the active electrode reservoir, to achieve application of the general methods described. The apparatus may include a sensor means therein, for use as feedback to a control system during operation. Methods and systems involving diffusion type delivery are also described.

摘要翻译： 描述了控制环境电传输的方法。 该方法通常涉及在电运输系统中控制活性电极池的离子环境。 该控制可以用于例如维持恒定的外来离子存在，例如pH。 也可以以优选的方式施用，以便在存在外来离子的情况下保持对目标物种的输送速率的选择性控制。 还描述了可用于提供受控环境电传输的设备。 通常，该装置包括电传输系统，其包括其中具有主电极布置和次电极布置的有源电极储存器，具有用于两者的选择操作的控制装置。 选择与主电极装置不同的次级电极装置用于操作以选择性地增强或以其它方式改变活性电极储存器中的离子存在，以实现所述的一般方法的应用。 该装置可以包括其中的传感器装置，用于在操作期间用作对控制系统的反馈。 还描述了涉及扩散型输送的方法和系统。

公开(公告)号：US5533971A

公开(公告)日：1996-07-09

申请号：US116660

申请日：1993-09-03

申请人： Joseph B. Phipps

发明人： Joseph B. Phipps

IPC分类号： A61N1/30

CPC分类号： A61N1/30

摘要： An electrotransport delivery device utilizing reservoir buffering at a select pH ranges in order to reduce skin irritation and skin resistance is provided. Cathodic reservoirs are buffered to a pH of less than about 4, preferably to a pH in the range of about 2 to 4, while anodic reservoirs are buffered to a pH above about 4, preferably to a pH in the range of about 4 to 10. Another electrotransport delivery device utilizes a potassium sensor to monitor potassium efflux from the skin. Potassium efflux above a certain predetermined level has been found to be a precursor to skin irritation/erythema. Operation of the device is modified (eg, terminated) when the predetermined potassium efflux level is sensed.

摘要翻译： 提供了一种在选择的pH范围内利用储存器缓冲以便减少皮肤刺激和皮肤抵抗的电输送输送装置。 阴极储存器缓冲至小于约4的pH，优选至约2至4范围内的pH，而阳极储存器缓冲至高于约4，优选至约4至10范围内的pH 另一种电输送装置利用钾传感器来监测来自皮肤的钾流出。 已经发现高于某一预定水平的钾流出物是皮肤刺激/红斑的前体。 当检测到预定的钾流出水平时，装置的操作被修改（例如，终止）。

公开(公告)号：US5443442A

公开(公告)日：1995-08-22

申请号：US173149

申请日：1993-12-22

申请人： Joseph B. Phipps ,  Lyn C. Moodie

发明人： Joseph B. Phipps ,  Lyn C. Moodie

IPC分类号： A61N1/30

CPC分类号： A61N1/044 ,  A61N1/0448 ,  A61N1/0436 ,  A61N1/0444

摘要： Methods for conducting controlled environment electrotransport are described. The methods generally concern control of the ionic environment of the active electrode reservoir, in an electrotransport system. This control may be utilized, for example, to maintain a constant extraneous ion presence, such as pH. It may also be applied in a preferred manner to maintain selected control over the delivery rate of a target species, in time, in the presence of extraneous ions. Apparatus usable to provide for controlled environment electrotransport are also described. In general the apparatus comprises an electrotransport system including an active electrode reservoir having therein both a primary electrode arrangement and a secondary electrode arrangement, with a control arrangement for selected operation of both. The secondary electrode arrangement, being operated different from the primary electrode arrangement, is selected for operation to selectively enhance or otherwise modify ion presence in the active electrode reservoir, to achieve application of the general methods described. The apparatus may include a sensor means therein, for use as feedback to a control system during operation. Methods and systems involving diffusion type delivery are also described.