公开(公告)号：US07879019B2

公开(公告)日：2011-02-01

申请号：US11925466

申请日：2007-10-26

申请人： John T. Santini, Jr. ,  Michael J. Cima ,  Robert S. Langer ,  Dennis Ausiello ,  Norman F. Sheppard, Jr.

发明人： John T. Santini, Jr. ,  Michael J. Cima ,  Robert S. Langer ,  Dennis Ausiello ,  Norman F. Sheppard, Jr.

IPC分类号： A61M31/00

CPC分类号： A61K9/0051 ,  A61F9/0017 ,  A61K9/0009 ,  A61K9/0048 ,  A61K9/0097 ,  H01L24/96 ,  H01L2924/01004 ,  H01L2924/01005 ,  H01L2924/01006 ,  H01L2924/01011 ,  H01L2924/01013 ,  H01L2924/01015 ,  H01L2924/0102 ,  H01L2924/01027 ,  H01L2924/01033 ,  H01L2924/01074 ,  H01L2924/01075 ,  H01L2924/01079 ,  H01L2924/014 ,  H01L2924/12041 ,  H01L2924/12042 ,  H01L2924/12043 ,  H01L2924/14 ,  H01L2924/1461 ,  H01L2924/19041 ,  H01L2924/19043 ,  H01L2924/00

摘要： A method is provided for selectively opening a containment reservoir. The method includes providing a device which comprises a substrate in which at least one reservoir is located and covered by a reservoir cap; and directing laser light to the reservoir cap to cause the reservoir cap to disintegrate or become permeable. The device may be an implantable medical device. The reservoirs may contain a drug for controlled release or a biosensor.

摘要翻译： 提供了一种用于选择性地打开容纳储存器的方法。 该方法包括提供一种装置，其包括基板，其中至少一个储存器定位并被储存器盖覆盖; 并将激光引导到储存器盖以使储存器盖分解或变得可渗透。 该装置可以是可植入医疗装置。 储存器可以含有用于控制释放的药物或生物传感器。

公开(公告)号：US07820201B2

公开(公告)日：2010-10-26

申请号：US11876153

申请日：2007-10-22

申请人： Wendy E. Pryce Lewis ,  Charles W. Rowe ,  Michael J. Cima ,  Peter A. Materna

发明人： Wendy E. Pryce Lewis ,  Charles W. Rowe ,  Michael J. Cima ,  Peter A. Materna

IPC分类号： A61K9/24 ,  A61K9/20 ,  A61K9/22 ,  A61K9/48

CPC分类号： A61K9/2893 ,  A61J3/10 ,  A61K9/2018 ,  A61K9/2027 ,  A61K9/2054 ,  A61K9/209 ,  A61K9/2095 ,  B33Y70/00 ,  B33Y80/00

摘要： The present invention includes controlled release dosage forms and methods of designing and manufacturing dosage forms to obtain specific release profiles, for example, zero-order release profiles, escalating release profiles or decreasing release profiles. The dosage forms of the present invention can include spatial variation of API concentration in the dosage form and can include nested regions. Dosage forms according to the present invention may be manufactured by any appropriate method for obtaining the internal structure as disclosed herein for producing zero-order release profiles and increasing or decreasing release profiles. The invention further includes methods of manufacturing such dosage forms, such as by three-dimensional printing, possibly also including compression of the dosage form after three-dimensional printing. The invention further includes methods of designing such dosage forms. Release profiles from non-uniform distributions of API concentration may be predicted based on simple experiments with uniform-concentration dosage forms.

摘要翻译： 本发明包括控制释放剂型和设计和制造剂型以获得特定释放特征的方法，例如零级释放曲线，升级释放曲线或减少释放曲线。 本发明的剂型可以包括剂型中API浓度的空间变化，并且可以包括嵌套区域。 根据本发明的剂型可以通过用于获得本文公开的用于产生零级释放曲线和增加或减少释放曲线的内部结构的任何适当方法来制造。 本发明还包括制造这种剂型的方法，例如通过三维印刷，可能还包括在三维印刷后压制剂型。 本发明还包括设计这种剂型的方法。 可以基于使用均匀浓度剂型的简单实验来预测API浓度不均匀分布的释放曲线。

公开(公告)号：US07776024B2

公开(公告)日：2010-08-17

申请号：US11925507

申请日：2007-10-26

申请人： John T. Santini, Jr. ,  Michael J. Cima ,  Robert S. Langer ,  Dennis Ausiello ,  Norman F. Sheppard, Jr.

发明人： John T. Santini, Jr. ,  Michael J. Cima ,  Robert S. Langer ,  Dennis Ausiello ,  Norman F. Sheppard, Jr.

IPC分类号： A61M31/00

CPC分类号： A61K9/0051 ,  A61F9/0017 ,  A61K9/0009 ,  A61K9/0048 ,  A61K9/0097 ,  H01L24/96 ,  H01L2924/01004 ,  H01L2924/01005 ,  H01L2924/01006 ,  H01L2924/01011 ,  H01L2924/01013 ,  H01L2924/01015 ,  H01L2924/0102 ,  H01L2924/01027 ,  H01L2924/01033 ,  H01L2924/01074 ,  H01L2924/01075 ,  H01L2924/01079 ,  H01L2924/014 ,  H01L2924/12041 ,  H01L2924/12042 ,  H01L2924/12043 ,  H01L2924/14 ,  H01L2924/1461 ,  H01L2924/19041 ,  H01L2924/19043 ,  H01L2924/00

摘要： Methods are provided for medical treatment or diagnosis of a patient. The method includes implanting into the patient a device which comprises (i) a substrate in which at least one reservoir is located and covered by a first reservoir cap, (ii) a drug or sensor located in the reservoir, and (iii) control circuitry and a power source for disintegrating or permeabilizing the reservoir cap, and (iv) an external interface to receive incident light energy; and directing focused light to the external interface of the implanted device to actuate disintegration or permeabilization of the reservoir cap to release the drug or expose the sensor. The device may implanted onto or into the sclera or other tissue surface of the eye of the patient. The focused light may be laser light, which may be used to transmit power or data to the device.

摘要翻译： 提供了用于治疗或诊断患者的方法。 该方法包括向患者植入一种装置，该装置包括：（i）至少一个储存器定位并被第一储存器盖覆盖的基底，（ii）位于储存器中的药物或传感器，以及（iii）控制电路 以及用于使储存器盖分解或渗透的电源，以及（iv）外部接口以接收入射光能; 并将聚焦的光引导到植入装置的外部界面以致驱动贮存器盖的分解或透化以释放药物或暴露传感器。 该装置可植入患者眼睛的巩膜或其他组织表面上或其中。 聚焦光可以是激光，其可以用于将功率或数据传输到设备。

公开(公告)号：US20100136517A1

公开(公告)日：2010-06-03

申请号：US12599109

申请日：2008-05-07

申请人： Grace Y. Kim ,  Christophoros C. Vassiliou ,  Karen D. Daniel ,  Michael J. Cima

发明人： Grace Y. Kim ,  Christophoros C. Vassiliou ,  Karen D. Daniel ,  Michael J. Cima

IPC分类号： C12Q1/70 ,  G01N33/544 ,  C12Q1/68 ,  G01N33/53

CPC分类号： G01N33/558

摘要： Methods and apparatus for stabilization of aggregation-based assays are described. In various embodiments, anti-analytes are dispersed within a matrix. A solution containing analytes brought into contact with the matrix, so that analytes may permeate throughout at least a portion of the matrix. In some embodiments, the anti-analytes and analytes are mobile within the matrix. As aggregates form and increase in size, the aggregates become substantially immobile within the matrix. As a result, signals representative of an amount of aggregation within the matrix can remain substantially constant. In various aspects, matrix-stabilized aggregation-based assays provide for reliable quantitative analysis of analyte concentration with test solutions.

摘要翻译： 描述了基于聚集的测定法的稳定化方法和装置。 在各种实施方案中，抗分析物分散在基质内。 含有与基质接触的分析物的溶液，使得分析物可渗透至基质的至少一部分。 在一些实施方案中，抗分析物和分析物在基质内是可移动的。 随着聚集体的形成和尺寸的增加，聚集体在基质内基本上不能移动。 结果，表示矩阵内的聚集量的信号可以保持基本恒定。 在各个方面，基于基质稳定聚集的测定提供了使用测试溶液的分析物浓度的可靠定量分析。

公开(公告)号：US20090149833A1

公开(公告)日：2009-06-11

申请号：US12333182

申请日：2008-12-11

申请人： Michael J. Cima ,  Heejin Lee

发明人： Michael J. Cima ,  Heejin Lee

IPC分类号： A61M25/00 ,  A61K31/167

CPC分类号： A61M25/0102 ,  A61F2250/0068 ,  A61K9/0024 ,  A61K9/0034 ,  A61K31/167 ,  A61M25/0108 ,  A61M31/002 ,  A61M2205/0216 ,  A61M2210/1085

摘要： An implantable medical device is provided for controlled drug delivery within the bladder, or other body vesicle. The device may include at least one drug reservoir component comprising a drug; and a vesicle retention frame which comprises an elastic wire having a first end, an opposing second end, and an intermediate region therebetween, wherein the drug reservoir component is attached to the intermediate region of the vesicle retention frame. The retention frame prevents accidental voiding of the device from the bladder, and it preferably has a spring constant selected for the device to effectively stay in the bladder during urination while minimizing the irritation of the bladder.

摘要翻译： 提供可植入的医疗装置用于膀胱或其他体内囊泡内的受控药物输送。 该装置可以包括至少一个包含药物的药物储存器部件; 以及囊泡保持框架，其包括具有第一端，相对的第二端和在其间的中间区域的弹性线，其中所述药物储存部件附接到所述囊泡保持框架的中间区域。 保持框架防止装置从膀胱意外排空，并且其优选地具有选择用于装置的弹簧常数，以在排尿期间有效地停留在膀胱中，同时使膀胱的刺激最小化。

公开(公告)号：US20090112188A1

公开(公告)日：2009-04-30

申请号：US12348609

申请日：2009-01-05

申请人： John T. Santini, JR. ,  Michael J. Cima ,  Scott Albert Uhland

发明人： John T. Santini, JR. ,  Michael J. Cima ,  Scott Albert Uhland

IPC分类号： A61K9/22

CPC分类号： B01L3/50853 ,  A61K9/0009 ,  A61K9/0024 ,  A61K9/0097 ,  B01L2300/0819 ,  B01L2400/0677

摘要： Microchip devices are provided that include a substrate; a plurality of reservoirs in the substrate, each reservoir defining an internal volume; and a reservoir cap positioned on or in each of the reservoirs bounding the internal volume from an external environment, the reservoir cap being formed of a material that undergoes a phase change upon heating, wherein the internal volume can communicate with the external environment upon heating said reservoir cap to cause said reservoir cap to undergo a phase change and rupture.

摘要翻译： 提供了包括衬底的Microchip器件; 在所述基板中的多个储存器，每个储存器限定内部容积; 以及储存器盖，其定位在从外部环境限定内部容积的每个储存器中或每个储存器中，所述储存器盖由在加热时经历相变的材料形成，其中所述内部容积可以在加热所述内部体积时与外部环境连通 储存器盖以使所述储存器盖发生相变和破裂。

公开(公告)号：US20080257718A1

公开(公告)日：2008-10-23

申请号：US11881830

申请日：2007-07-26

申请人： Yet-Ming Chiang ,  Michael J. Cima ,  Timothy E. Chin

发明人： Yet-Ming Chiang ,  Michael J. Cima ,  Timothy E. Chin

IPC分类号： C25B9/00

CPC分类号： F03G7/005 ,  H01M2/16 ,  H01M4/485 ,  H01M4/505 ,  H01M4/525 ,  H01M4/587 ,  H01M6/30 ,  H01M2004/021 ,  H01M2010/4292

摘要： The present invention provides systems, devices, and related methods, involving electrochemical actuation. In some cases, application of a voltage or current to a system or device of the invention may generate a volumetric or dimensional change, which may produce mechanical work. For example, at least a portion of the system may be constructed and arranged to be displaced from a first orientation to a second orientation. Systems such as these may be useful in various applications, including pumps (e.g., infusion pumps) and drug delivery devices, for example.

摘要翻译： 本发明提供涉及电化学致动的系统，装置和相关方法。 在一些情况下，将电压或电流施加到本发明的系统或装置可能产生容积或尺寸变化，这可能产生机械作业。 例如，系统的至少一部分可以被构造和布置成从第一取向向第二取向移位。 诸如这些的系统可用于各种应用，例如泵（例如输注泵）和药物输送装置。

公开(公告)号：US07354597B2

公开(公告)日：2008-04-08

申请号：US10308579

申请日：2002-12-03

申请人： Audrey M. Johnson ,  Michael J. Cima ,  Robert S. Langer

发明人： Audrey M. Johnson ,  Michael J. Cima ,  Robert S. Langer

IPC分类号： A61F2/02 ,  A61K9/14

CPC分类号： F26B5/06

摘要： Methods and systems are provided for microscale lyophilization or microscale drying of agents of interest, such as pharmaceutical agents or other molecules that are unstable or easily degraded in solution. The drying method includes (a) providing a liquid comprising an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing a microquantity (between 1 nL and 10 μL) of the liquid onto a preselected site of a substrate; and then (c) drying the microquantity by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest. The lyophilization method includes freezing the microquantity of liquid after step (b) and before step (c). By processing the agent of interest in microquantities in controlled contact with a substrate surface, improved heat and mass transfer is provided, yielding better process control over drying of the agent of interest compared to conventional bulk drying or lyophilization.

摘要翻译： 提供的方法和系统用于微量冻干或微量干燥感兴趣的试剂，例如不稳定或容易在溶液中降解的药剂或其它分子。 干燥方法包括（a）提供包含溶解或分散在挥发性液体介质中的感兴趣剂的液体; （b）将液体的微量（在1nL和10μL之间）沉积到衬底的预选位置; 然后（c）通过挥发挥发性液体介质来干燥微量，以产生干燥，固体形式的感兴趣的试剂。 冻干方法包括在步骤（b）之后和步骤（c）之前冷冻液体的微量。 通过加工与基材表面受控接触的微量级的感兴趣的试剂，提供了改进的热和质量传递，与传统的大体积干燥或冻干相比，可以对感兴趣的试剂的干燥产生更好的工艺控制。

公开(公告)号：US07276252B2

公开(公告)日：2007-10-02

申请号：US09861480

申请日：2001-05-18

申请人： Francis C. Payumo ,  Jill K. Sherwood ,  Donald C. Monkhouse ,  Jaedeok Yoo ,  Christopher M. Gaylo ,  Chen-Chao Wang ,  Michael J. Cima

发明人： Francis C. Payumo ,  Jill K. Sherwood ,  Donald C. Monkhouse ,  Jaedeok Yoo ,  Christopher M. Gaylo ,  Chen-Chao Wang ,  Michael J. Cima

IPC分类号： A61K9/26

CPC分类号： A61K9/2893 ,  A61K9/209 ,  A61K9/2886 ,  B33Y10/00 ,  B33Y70/00 ,  B33Y80/00

摘要： A drug delivery device such as an oral dosage form (ODF) with a toxic or potent core encapsulated by a non-toxic region. The non-toxic region may be a region including multiple layers, coatings, shells, and combinations thereof, which provides protection to and isolation from the toxic or potent core. The drug in the toxic or potent core is incorporated into the dosage form via, for example, three-dimensional printing, as a solution, solubilization or suspension of solid particles in liquid, rather than by the more conventional handling and compressing of dry powder. This minimizes the likelihood of creating airborne particles of the toxic drug during manufacturing, hence controlling and minimizing the exposure of manufacturing personnel to the hazardous substance. Wet dispensing of the toxic or potent drug further provides greater bioavailability of the drug to the patient.

摘要翻译： 药物递送装置，例如具有由无毒区域包封的毒性或有效核心的口服剂型（ODF）。 无毒区域可以是包括多层，涂层，壳及其组合的区域，其提供对有毒或有效的核心的保护和分离。 有毒或有效的核心中的药物通过例如三维印刷作为溶液，固体颗粒在液体中的溶解或悬浮而不是通过更常规的干粉处理和压缩而被并入到剂型中。 这最小化在制造过程中产生毒性药物的空气中颗粒的可能性，从而控制和最小化制造人员对有害物质的暴露。 有毒或有效的药物的湿分配进一步提供药物对患者更大的生物利用度。

公开(公告)号：US07172859B2

公开(公告)日：2007-02-06

申请号：US10371372

申请日：2003-02-20

申请人： Michael J. Cima ,  Hongming Chen ,  J. Richard Gyory

发明人： Michael J. Cima ,  Hongming Chen ,  J. Richard Gyory

IPC分类号： C12Q1/00

CPC分类号： G01N33/5088 ,  G01N13/00

摘要： The present invention relates to high-throughput systems and methods to prepare a large number of component combinations, at varying concentrations and identities, at the same time, and high-throughput methods to test tissue barrier transfer, such as transdermal transfer, of components in each combination. The methods of the present invention allow determination of the effects of inactive components, such as solvents, excipients, enhancers, adhesives and additives, on tissue barrier transfer of active components, such as pharmaceuticals. The invention thus encompasses the high-throughput testing of pharmaceutical compositions or formulations in order to determine the overall optimal composition or formulation for improved tissue transport, such as transdermal transport.

摘要翻译： 本发明涉及高通量系统和方法，以同时以不同的浓度和同一性制备大量组分组合，以及高通量方法来测试组织屏障转移，例如透皮转移 每个组合。 本发明的方法允许测定非活性组分如溶剂，赋形剂，增强剂，粘合剂和添加剂对活性组分如药物的组织屏障转移的影响。 因此，本发明包括药物组合物或制剂的高通量测试，以便确定用于改善组织转运的总体最佳组合物或制剂，例如透皮转运。