公开(公告)号：US4344929A

公开(公告)日：1982-08-17

申请号：US228091

申请日：1981-01-26

申请人： Pieter Bonsen ,  Patrick S. Wong ,  Felix Theeuwes

发明人： Pieter Bonsen ,  Patrick S. Wong ,  Felix Theeuwes

IPC分类号： A61K9/00 ,  A61K9/46 ,  A61J1/00

CPC分类号： A61K9/0004

摘要： A method is disclosed for delivering a drug substantially-free of rapid precipitation from an osmotic device. The osmotic device comprises a semipermeable wall surrounding a compartment housing (1) a drug that exhibits limited solubility under neutral and acid conditions, and (2) a compound capable of evolving carbon dioxide in the presence of an acid in the environment of use. The method comprises, (a) imbibing fluid through the wall into the compartment at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, (b) forming in the compartment a basic solution containing drug and compound, which solution is delivered from the compartment through the passageway, (c) reacting the compound with the acid in the environment at the device-environment interface for evolving carbon dioxide, thereby, (d) providing an effervescent suspension in the environment that delivers the drug in a finely dispersed form to the environment of use over time. Also, a composition is disclosed comprising the drug and the compound.

摘要翻译： 公开了用于从渗透装置输送基本上不含快速沉淀的药物的方法。 渗透装置包括围绕隔室壳体（1）的半透壁，其在中性和酸性条件下表现出有限的溶解性，和（2）能够在使用环境中存在酸的情况下能够释放二氧化碳的化合物。 该方法包括：（a）将流体通过所述壁吸入所述隔室中，所述速率由所述壁的渗透性和穿过所述壁的渗透压梯度确定，（b）在所述室中形成含有药物和化合物的碱性溶液， 溶液通过通道从隔室输送，（c）使化合物与环境中的酸在设备 - 环境界面反应，用于放出二氧化碳，从而（d）在环境中提供泡腾悬浮液，将环境中的药物递送 随着时间的推移，使用环境的细分散形式。 另外，公开了包含药物和化合物的组合物。

公开(公告)号：US20130028953A1

公开(公告)日：2013-01-31

申请号：US13486711

申请日：2012-06-01

申请人： Su II Yum ,  Felix Theeuwes

发明人： Su II Yum ,  Felix Theeuwes

IPC分类号： A61K9/70 ,  A61P29/00 ,  A61K31/4535

CPC分类号： A61K9/703 ,  A61F2013/0296 ,  A61K9/7053 ,  A61K9/7061 ,  A61K9/7084 ,  A61K31/445 ,  A61K31/4535 ,  A61M35/00

摘要： Transdermal delivery systems for administering sufentanil through the skin are provided. The systems contain a sufficient amount of sufentanil to induce and maintain a constant state of analgesia when applied to a subject. The systems are characterized as having one or more features including a high degree of dosage form rate control over flux of sufentanil from the system, a high net flux of sufentanil from the system through the skin, lack of a permeation enhancer, an adhesive member demonstrating superior shear time, a low coefficient of variation in the net flux of sufentanil from the system, a high delivery efficiency, and a substantially constant steady state net flux of sufentanil from the system. Methods of using the transdermal delivery systems to administer a sufficient amount of sufentanil to induce and maintain analgesia for extended periods when applied to a subject are also provided.

摘要翻译： 提供了通过皮肤施用舒芬太尼的透皮递送系统。 当施用于受试者时，该系统含有足量的舒芬太尼以诱导和保持恒定的止痛状态。 该系统的特征在于具有一个或多个特征，其包括对来自系统的舒芬太尼的通量的高剂量形式速率控制，来自系统通过皮肤的舒芬太尼的高净通量，缺乏渗透促进剂， 优异的剪切时间，来自系统的舒芬太尼的净通量的低变异系数，高的输送效率和来自系统的舒芬太尼的稳定的稳态净通量。 还提供了使用透皮递送系统施用足够量的舒芬太尼以在施用于受试者时延长期间诱导和维持止痛的方法。

公开(公告)号：US08246977B2

公开(公告)日：2012-08-21

申请号：US11665813

申请日：2005-10-21

申请人： Su Il Yum ,  Felix Theeuwes

发明人： Su Il Yum ,  Felix Theeuwes

IPC分类号： A61K9/70 ,  A61K31/445

CPC分类号： A61K9/703 ,  A61F2013/0296 ,  A61K9/7053 ,  A61K9/7061 ,  A61K9/7084 ,  A61K31/445 ,  A61K31/4535 ,  A61M35/00

摘要： Transdermal delivery systems for administering sufentanil through the skin are provided. The systems contain a sufficient amount of sufentanil to induce and maintain a constant state of analgesia when applied to a subject. The systems are characterized as having one or more features including a high degree of dosage form rate control over flux of sufentanil from the system, a high net flux of sufentanil from the system through the skin, lack of a permeation enhancer, an adhesive member demonstrating superior shear time, a low coefficient of variation in the net flux of sufentanil from the system, a high delivery efficiency, and a substantially constant steady state net flux of sufentanil from the system. Methods of using the transdermal delivery systems to administer a sufficient amount of sufentanil to induce and maintain analgesia for extended periods when applied to a subject are also provided.

摘要翻译： 提供了通过皮肤施用舒芬太尼的透皮递送系统。 当施用于受试者时，该系统含有足量的舒芬太尼以诱导和保持恒定的止痛状态。 该系统的特征在于具有一个或多个特征，其包括对来自系统的舒芬太尼的通量的高剂量形式速率控制，来自系统通过皮肤的舒芬太尼的高净通量，缺乏渗透促进剂， 优异的剪切时间，来自系统的舒芬太尼的净通量的低变异系数，高的输送效率和来自系统的舒芬太尼的稳定的稳态净通量。 还提供了使用透皮递送系统施用足够量的舒芬太尼以在施用于受试者时延长期间诱导和维持止痛的方法。

公开(公告)号：US20100016267A1

公开(公告)日：2010-01-21

申请号：US10592886

申请日：2005-03-15

申请人： Felix Theeuwes ,  Arthur J. Tipton

发明人： Felix Theeuwes ,  Arthur J. Tipton

IPC分类号： A61K31/58 ,  A61P27/00

CPC分类号： A61K9/0043

摘要： Pharmaceutical compositions for delivering a drug to a sinus in a subject are provided. The compositions are formed by the combination of a carrier material and a drug and are specially adapted for delivery to a sinus. The compositions have no fixed shape, and the carrier material serves to increase the viscosity or specific volume of the composition after introduction of the composition into the sinus. Also provided are methods for delivering a drug to a subject. The methods entail administering a pharmaceutical composition according to the present invention directly to a sinus. The drug is then released from the composition to the sinus. The pharmaceutical compositions can be administered to a sinus in liquid form, for example, as a suspension or solution using standard techniques. Also provided is the use of a carrier material in the manufacture of a drug delivery composition. The drug delivery composition is for delivering a drug to a sinus in a subject. The composition comprises the carrier material combined with the drug to be delivered, and has no fixed shape. After the composition is introduced into a sinus, the carrier material serves to increase the viscosity or specific volume of the composition.

摘要翻译： 提供用于将药物递送至受试者的窦的药物组合物。 组合物通过载体材料和药物的组合形成，并且特别适于递送至窦。 组合物没有固定的形状，并且载体材料用于在将组合物引入窦内后增加组合物的粘度或比体积。 还提供了将药物递送到受试者的方法。 所述方法需要将根据本发明的药物组合物直接给予鼻窦。 然后将药物从组合物释放到窦。 药物组合物可以以液体形式施用于窦，例如使用标准技术作为悬浮液或溶液施用。 还提供了载体材料在制备药物递送组合物中的用途。 药物递送组合物用于将药物递送至受试者的窦。 该组合物包含与待输送药物结合的载体材料，并且不具有固定形状。 在将组合物引入窦中之后，载体材料用于增加组合物的粘度或比体积。

公开(公告)号：US20080260811A1

公开(公告)日：2008-10-23

申请号：US11888661

申请日：2007-07-31

申请人： Su Il Yum ,  Felix Theeuwes

发明人： Su Il Yum ,  Felix Theeuwes

IPC分类号： A61K31/4436 ,  A61K9/70 ,  A61P43/00

CPC分类号： A61K31/4535 ,  A61F2013/0296 ,  A61K9/7053 ,  A61K9/7061 ,  A61K9/7084

摘要： Transdermal delivery systems for administering sufentanil through the skin are provided. The systems contain a sufficient amount of sufentanil to induce and maintain a constant state of analgesia when applied to a subject. The systems are characterized as having one or more features including a high degree of dosage form rate control over flux of sufentanil from the system, a high net flux of sufentanil from the system through the skin, lack of a permeation enhancer, an adhesive member demonstrating superior shear time, a low coefficient of variation in the net flux of sufentanil from the system, a high delivery efficiency, and a substantially constant steady state net flux of sufentanil from the system. Methods of using the transdermal delivery systems to administer a sufficient amount of sufentanil to induce and maintain analgesia for extended periods when applied to a subject are also provided.

摘要翻译： 提供了通过皮肤施用舒芬太尼的透皮递送系统。 当施用于受试者时，该系统含有足量的舒芬太尼以诱导和保持恒定的止痛状态。 该系统的特征在于具有一个或多个特征，其包括对来自系统的舒芬太尼的通量的高剂量形式速率控制，来自系统通过皮肤的舒芬太尼的高净通量，缺乏渗透促进剂， 优异的剪切时间，来自系统的舒芬太尼的净通量的低变异系数，高的输送效率和来自系统的舒芬太尼的稳定的稳态净通量。 还提供了使用透皮递送系统施用足够量的舒芬太尼以在施用于受试者时延长期间诱导和维持止痛的方法。

公开(公告)号：US20080175890A1

公开(公告)日：2008-07-24

申请号：US11888650

申请日：2007-07-31

申请人： Su Il Yum ,  Felix Theeuwes

发明人： Su Il Yum ,  Felix Theeuwes

IPC分类号： A61K31/4535 ,  A61K9/70 ,  A61P31/00

CPC分类号： A61K31/4535 ,  A61F2013/0296 ,  A61K9/7053 ,  A61K9/7061 ,  A61K9/7084

摘要： Transdermal delivery systems for administering sufentanil through the skin are provided. The systems contain a sufficient amount of sufentanil to induce and maintain a constant state of analgesia when applied to a subject. The systems are characterized as having one or more features including a high degree of dosage form rate control over flux of sufentanil from the system, a high net flux of sufentanil from the system through the skin, lack of a permeation enhancer, an adhesive member demonstrating superior shear time, a low coefficient of variation in the net flux of sufentanil from the system, a high delivery efficiency, and a substantially constant steady state net flux of sufentanil from the system. Methods of using the transdermal delivery systems to administer a sufficient amount of sufentanil to induce and maintain analgesia for extended periods when applied to a subject are also provided.

公开(公告)号：US20070167932A1

公开(公告)日：2007-07-19

申请号：US11726517

申请日：2007-03-21

申请人： Felix Theeuwes ,  Su Yum

发明人： Felix Theeuwes ,  Su Yum

IPC分类号： A61K9/22

CPC分类号： A61M25/00 ,  A61M25/0043 ,  A61M2025/0057 ,  A61M2025/105 ,  A61M2025/1086

摘要： The invention provides a local concentration management system (LCMS) for delivery of highly concentrated therapeutic agent formulations. The LCMS comprises a device comprising an elongate body defining a lumen between its proximal and distal ends, and a diffuser element, a dilutor element, or both. The diffuser element, which is selectively permeable to the agent, is operatively associated with the elongate body so that agent flows through the elongate body, and into and through the diffuser element to exit the system. The dilutor element can be operatively associated with the system to be in fluid communication with the elongate body lumen, a diffusion space defined by a diffuser element inner wall, or both. The dilutor element is selectively water permeable, but substantially impermeable to agent, to provide for dilution of the agent during transit through the system. The LCMS system is designed to disperse and/or dilute the drug delivery stream.

摘要翻译： 本发明提供了用于递送高度浓缩的治疗剂制剂的局部浓度管理系统（LCMS）。 LCMS包括装置，其包括在其近端和远端之间限定内腔的细长主体，以及扩散器元件，稀释元件或两者。 对试剂选择性渗透的扩散器元件可与细长体可操作地连接，使得试剂流过细长体并进入并通过扩散器元件以离开系统。 稀释元件可以与系统可操作地相关联以与细长体腔流体连通，由扩散器元件内壁或两者限定的扩散空间。 稀释剂元件选择性地是水可渗透的，但是对试剂基本上是不可渗透的，以便在通过系统运输期间提供试剂的稀释。 LCMS系统被设计成分散和/或稀释药物输送流。

公开(公告)号：US07212853B1

公开(公告)日：2007-05-01

申请号：US08952368

申请日：1996-06-07

申请人： J. Bradley Phipps ,  Gary A. Lattin ,  Ronald P. Haak ,  Felix Theeuwes ,  Suneel K. Gupta

发明人： J. Bradley Phipps ,  Gary A. Lattin ,  Ronald P. Haak ,  Felix Theeuwes ,  Suneel K. Gupta

IPC分类号： A61N1/30

CPC分类号： A61N1/325 ,  A61N1/044 ,  A61N1/0448

摘要： An electrotransport agent delivery device (10) for delivering a therapeutic agent through intact skin, and a method of operating same, is provided. The device applies a pulsing electrotransport current wherein current pulses have a magnitude above a critical level (Ic) at which the skin is transformed into a higher electrotransport delivery efficiency (E) state. Most preferably the length of the applied current pulses is at least 5 msec and preferably at least 10 msec.

摘要翻译： 提供了一种用于通过完整皮肤递送治疗剂的电转运剂递送装置（10）及其操作方法。 该装置施加脉冲电输送电流，其中电流脉冲具有高于皮肤转化为更高的电转运递送效率（E）状态的临界水平（I C）以上的幅度。 最优选地，施加的电流脉冲的长度为至少5毫秒，优选至少10毫秒。

公开(公告)号：US20060129139A1

公开(公告)日：2006-06-15

申请号：US11353842

申请日：2006-02-14

申请人： Felix Theeuwes ,  Ben Eckenhoff ,  Bonnie Dennis

发明人： Felix Theeuwes ,  Ben Eckenhoff ,  Bonnie Dennis

IPC分类号： A61K9/22

CPC分类号： A61K9/0004

摘要： An osmotic delivery system having a space-efficient piston is provided. The enclosure has an interior holding the piston, a protein or polypeptide, and an osmotic agent. The piston is movable with respect to an interior surface of the capsule, and defines a movable seal with the interior surface of the capsule. The movable seal separates the osmopolymer from the protein or polypeptide. The piston has a recess that receives at least a portion of the osmotic agent. The osmotic agent imbibes liquid from a surrounding environment to cause the piston to move and in turn cause delivery of the beneficial agent from the capsule.

摘要翻译： 提供了具有节省空间的活塞的渗透输送系统。 外壳具有保持活塞，蛋白质或多肽和渗透剂的内部。 活塞可相对于胶囊的内表面移动，并且与胶囊的内表面限定可移动的密封。 可移动密封将渗透聚合物与蛋白质或多肽分开。 活塞具有容纳渗透剂的至少一部分的凹部。 渗透剂吸收来自周围环境的液体以使活塞移动，从而导致有益剂从胶囊的输送。

公开(公告)号：US6049733A

公开(公告)日：2000-04-11

申请号：US938769

申请日：1997-09-26

申请人： J. Bradley Phipps ,  Lyn C. Moodie ,  J. Richard Gyory ,  Felix Theeuwes

发明人： J. Bradley Phipps ,  Lyn C. Moodie ,  J. Richard Gyory ,  Felix Theeuwes

IPC分类号： A61N1/30

CPC分类号： A61N1/0448 ,  A61N1/0444 ,  Y10S977/949

摘要： An electrotransport apparatus using dispersed ion exchange material (19,83) is disclosed. The ion exchange material (19,83) may be dispersed in either the donor electrode assembly (10), the counter electrode assembly (10) or both electrode assemblies. The dispersed ion exchange material (83) comprises mobile ionic species (84-2) and substantially immobile ionic species (P). The dispersed ion exchange material (83, 84-2) interacts with competitive species (86) generated during electrotransport to render those species substantially immobile (87). Electrotransport devices exhibiting reduced polarization are also disclosed.

摘要翻译： 公开了一种使用分散离子交换材料（19,83）的电转运装置。 离子交换材料（19,83）可以分散在供体电极组件（10），对电极组件（10）或两个电极组件中。 分散的离子交换材料（83）包括移动离子物质（84-2）和基本上不可移动的离子物质（P）。 分散的离子交换材料（83,84-2）与在电输运期间产生的竞争物种（86）相互作用以使这些物质基本上不可移动（87）。 还公开了表现出减小的极化的电子传输器件。