公开(公告)号：US07377939B2

公开(公告)日：2008-05-27

申请号：US10988814

申请日：2004-11-15

申请人： Michael S. Williams ,  Robert S. Langer ,  Yadong Wang

发明人： Michael S. Williams ,  Robert S. Langer ,  Yadong Wang

IPC分类号： A61F2/06

CPC分类号： A61F2/06 ,  A61L31/04 ,  A61L31/041 ,  A61L31/14 ,  A61L2400/16

摘要： Endolumenal prostheses that readily and extensively convert from a delivery configuration to a deployed configuration are disclosed. Endolumenal prostheses may be fabricated from one or more shape memory polymers, a high modulus elastomer, a polymer that is both elastomeric and exhibits shape memory behavior, a hydrogel, or some combination thereof. Polymers used to fabricate the prostheses are selectively synthesized to exhibit desired characteristics such as crystallinity, strain fixity rate, strain recovery rate, elasticity, tensile strength, mechanical strength, cross-linking density, extent physical cross-linking, extent of covalent cross-linking, extent of interpenetrating networks, rate of erosion, heat of fusion, crystallization temperature, and acidity during erosion. The endolumenal prostheses convert to the deployed configuration following delivery to a treatment site, upon exposure to an initiator either present within the body naturally or introduced into the body.

摘要翻译： 公开了容易且广泛地从输送配置转换成展开构型的腔内假体。 腔内假体可以由一种或多种形状记忆聚合物，高模量弹性体，弹性体和表现出形状记忆行为的聚合物，水凝胶或其某些组合制成。 用于制造假体的聚合物被选择性地合成以显示所需的特性，例如结晶度，应变固定率，应变恢复速率，弹性，拉伸强度，机械强度，交联密度，物理交联程度，共价交联程度 互穿网络的程度，侵蚀速率，熔化热，结晶温度和侵蚀过程中的酸度。 在暴露于身体内自然存在或引入体内的引发剂之后，腔内假体转化为部署构型。

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：US07077866B2

公开(公告)日：2006-07-18

申请号：US09785593

申请日：2001-02-16

申请人： Joseph D. Gresser ,  Debra J. Trantolo ,  Robert S. Langer ,  Kai-Uwe Lewandrowski ,  Alexander M. Klibanov ,  Donald L. Wise

发明人： Joseph D. Gresser ,  Debra J. Trantolo ,  Robert S. Langer ,  Kai-Uwe Lewandrowski ,  Alexander M. Klibanov ,  Donald L. Wise

IPC分类号： A61F2/44

CPC分类号： A61F2/4455 ,  A61F2/30965 ,  A61F2/442 ,  A61F2002/2835 ,  A61F2002/30062 ,  A61F2002/30112 ,  A61F2002/30133 ,  A61F2002/30153 ,  A61F2002/30179 ,  A61F2002/30217 ,  A61F2002/30772 ,  A61F2002/30785 ,  A61F2002/30789 ,  A61F2002/30868 ,  A61F2002/30904 ,  A61F2002/30957 ,  A61F2210/0004 ,  A61F2230/0004 ,  A61F2230/0015 ,  A61F2230/0019 ,  A61F2230/0058 ,  A61F2230/0067 ,  Y10S623/926

摘要： A resorbable interbody fusion device for use in spinal fixation is disclosed. The device is composed of 25–100% bioresorbable or resorbable material. The interbody fusion device of the invention can be in any convenient form, such as a wedge, screw or cage. Preferably, the resorbable device of the invention is in the shape of a tapered wedge or cone, which further desirably incorporates structural features such as serrations or threads better to anchor the device in the adjoining vertebrae. The preferred device further comprises a plurality of peripheral voids and more desirably a central void space therein, which may desirably be filled with a grafting material for facilitating bony development and/or spinal fusion, such as an autologous grafting material. As the preferred material from which the resorbable interbody fusion device is manufactured is most likely to be a polymer that can produce acidic products upon hydrolytic degradation, the device preferably further includes a neutralization compound, or buffer, in sufficiently high concentration to decrease the rate of pH change as the device degrades, in order to prevent sterile abscess formation caused by the accumulation of unbuffered acidic products in the area of the implant.

摘要翻译： 公开了一种用于脊柱固定的可再吸收体内融合装置。 该装置由25-100％的生物可吸收或可再吸收材料组成。 本发明的体内融合装置可以是任何方便的形式，例如楔形物，螺钉或笼子。 优选地，本发明的可再吸收装置是锥形楔形或锥形的形状，其进一步期望地包括诸如锯齿或线的结构特征，以更好地将装置锚定在相邻的椎骨中。 优选的装置还包括多个周边空隙，并且更期望地为其中的中心空隙空间，其可期望地填充有用于促进骨发育和/或脊柱融合的接枝材料，例如自体移植材料。 作为制造可再吸收的体内融合装置的优选材料最可能是在水解降解时可以产生酸性产物的聚合物，该装置优选还包含足够高浓度的中和化合物或缓冲剂，以降低 pH值随器械降解而改变，以防止在植入物区域积聚无缓冲酸性产物引起的无菌性脓肿形成。

公开(公告)号：US07070590B1

公开(公告)日：2006-07-04

申请号：US09665303

申请日：2000-09-19

申请人： John T. Santini, Jr. ,  Michael J. Cima ,  Robert S. Langer

发明人： John T. Santini, Jr. ,  Michael J. Cima ,  Robert S. Langer

IPC分类号： A61K9/22

CPC分类号： A61K9/0009 ,  A61K9/0024 ,  A61K9/0097 ,  A61M5/14276 ,  A61M37/00 ,  A61M2205/0244 ,  C25F5/00 ,  C25F7/00 ,  Y10T137/8242

摘要： Devices are provided for the controlled release of drug or other molecules. The devices include (1) a substrate, which optionally includes two or more substrate portions bonded together, (2) at least two reservoirs in the substrate, (3) a release system disposed in the reservoirs that includes the molecules for release and optionally a matrix material, and (4) active or passive means for controlling release of the molecules from the reservoirs. In one embodiment, a reservoir cap is positioned on, or within a portion of, the reservoir and over the molecules, so that the molecules are controllably released from the device by diffusion through or upon disintegration of the reservoir cap.

摘要翻译： 提供了用于药物或其他分子的控制释放的装置。 这些装置包括（1）基材，其任选地包括两个或更多个粘结在一起的基底部分，（2）基底中的至少两个储存器，（3）设置在储存器中的释放系统，其包括用于释放的分子， 基质材料，（4）用于控制分子从储层释放的主动或被动方式。 在一个实施例中，储存器盖位于储存器的一部分上，或位于储存器的一部分上方，并位于分子上方，使得分子通过扩散通过储存器盖的分解或分解而可控制地从装置释放。

公开(公告)号：US06977223B2

公开(公告)日：2005-12-20

申请号：US10794610

申请日：2004-03-05

申请人： Paul M. George ,  Robert S. Langer ,  David A. Lavan

发明人： Paul M. George ,  Robert S. Langer ,  David A. Lavan

IPC分类号： C25D1/00 ,  C25D1/10 ,  C25D3/38 ,  C25D5/02 ,  C25D5/16 ,  G02B6/124 ,  G02B6/13 ,  H01L21/288 ,  H01L21/768 ,  H01L21/44

CPC分类号： C25D1/00 ,  B81C99/0095 ,  C25D1/003 ,  C25D1/10 ,  C25D3/38 ,  C25D5/022 ,  C25D5/16 ,  G02B6/124 ,  G02B6/13 ,  H01L21/2885 ,  H01L21/76838

摘要： Method for making three-dimensional structures. A template is provided having at least two conductive regions separated by a non-conductive region. The template is disposed in an electrolyte in an electrodeposition cell and a voltage is established between one of the conductive regions and an electrode in the cell. Material is deposited on the one of the conductive regions connected to the voltage and subsequently bridges to the other conductive region with material deposition continuing on both of the at least two regions. The non conductive region may be a gap and the gap dimension is selected to regulate height differences between the at least two conductive regions.

摘要翻译： 制作三维结构的方法。 提供了具有由非导电区域隔开的至少两个导电区域的模板。 将模板设置在电沉积电池中的电解质中，并且在电池中的一个导电区域和电极之间建立电压。 材料沉积在连接到电压的导电区域中的一个上，并且随后在至少两个区域两者上继续材料沉积而桥接到另一个导电区域。 非导电区域可以是间隙，并且选择间隙尺寸以调节至少两个导电区域之间的高度差。

公开(公告)号：US06977087B2

公开(公告)日：2005-12-20

申请号：US10090418

申请日：2002-03-01

申请人： David A. Edwards ,  Giovannia Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

发明人： David A. Edwards ,  Giovannia Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

IPC分类号： A61K9/00 ,  A61K9/14 ,  A61K9/16 ,  A61K31/56 ,  A61K31/568 ,  A61K38/28

CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/56 ,  A61K31/568 ,  A61K38/28

摘要： Improved aerodynamically light particles for delivery to the pulmonary system, and methods for their preparation and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 μm and 30 μm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear α-hydroxy-acid polyester backbone having at least one amino acid group incorporated herein and at least on poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 μm, can be used for enhanced delivery of a therapeutic or diagnostic agent to the alveolar region of the lung. The aerodynamically light particles optionally can incorporate a therapeutic or diagnostic agent, and may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of a wide variety of incorporated agents.

摘要翻译： 提供用于递送至肺系统的改善的空气动力学轻微颗粒，以及其制备和给药方法。 在优选的实施方案中，空气动力学轻微颗粒由可生物降解的材料制成，并且振实密度小于0.4g / cm 3，质量平均直径在5μm和30μm之间。 颗粒可以由可生物降解的材料如可生物降解的聚合物形成。 例如，颗粒可以由官能化的聚酯接枝共聚物形成，所述官能化聚酯接枝共聚物由具有至少一个引入本文的氨基酸基团和至少在从氨基酸延伸的聚（氨基酸）侧链上的直链α-羟基酸聚酯主链组成 集团在聚酯骨干。 在一个实施方案中，具有大平均直径（例如大于5μm）的空气动力学轻的颗粒可用于增强治疗或诊断剂递送至肺的肺泡区域。 空气动力学轻微颗粒任选地可以掺入治疗剂或诊断剂，并且可以有效地雾化用于给予呼吸道以允许各种并入药剂的全身或局部递送。

公开(公告)号：US06720402B2

公开(公告)日：2004-04-13

申请号：US10141891

申请日：2002-05-08

申请人： Robert S. Langer ,  Andreas Lendlein

发明人： Robert S. Langer ,  Andreas Lendlein

IPC分类号： C08G1848

CPC分类号： G01K5/483 ,  A61B2017/00871 ,  B29C61/003 ,  C08L101/00 ,  Y10S525/903 ,  Y10S977/754

摘要： Shape memory polymer compositions, articles of manufacture thereof, and methods of preparation and use thereof are described. The shape memory polymer compositions can hold more than one shape in memory. Suitable compositions include at least one hard segment and at least one soft segment. At least one of the hard or soft segments can contain a crosslinkable group, and the segments can be linked by formation of an interpenetrating network or a semi-interpenetrating network, or by physical interactions of the blocks. Objects can be formed into a given shape at a temperature above the Ttrans of the hard segment, and cooled to a temperature below to Ttrans of the soft segment. If the object is subsequently formed into a second shape, the object can return to its original shape by heating the object above the Ttrans of the soft segment and below the Ttrans of the hard segment.

摘要翻译： 描述形状记忆聚合物组合物，其制备方法及其制备和使用方法。 形状记忆聚合物组合物可以在存储器中保持多于一种形状。 合适的组合物包括至少一个硬链段和至少一个软链段。 硬链段或软链段中的至少一个可以包含可交联基团，并且链段可以通过形成互穿网络或半互穿网络或通过块的物理相互作用而链接。 物体可以在高于硬链段的Ttrans的温度下形成给定的形状，并且被冷却到低于软链段的Ttrans的温度。 如果对象随后形成第二形状，则可以通过将软部分的Ttrans上方的物体加热到硬片段的Ttrans下面，物体可以返回到其原始形状。

公开(公告)号：US06689608B1

公开(公告)日：2004-02-10

申请号：US09669760

申请日：2000-09-26

申请人： Antonios G. Mikos ,  Robert S. Langer ,  Joseph P. Vacanti ,  Linda G. Griffith ,  Georgios Sarakinos

发明人： Antonios G. Mikos ,  Robert S. Langer ,  Joseph P. Vacanti ,  Linda G. Griffith ,  Georgios Sarakinos

IPC分类号： C12N506

CPC分类号： C08J9/28 ,  A61F2/0077 ,  A61F2/18 ,  A61F2/186 ,  A61F2/28 ,  A61F2/30756 ,  A61F2/3094 ,  A61F2/30942 ,  A61F2/4241 ,  A61F2002/30011 ,  A61F2002/30062 ,  A61F2002/30156 ,  A61F2002/30299 ,  A61F2002/30304 ,  A61F2002/30929 ,  A61F2002/30971 ,  A61F2002/4251 ,  A61F2210/0004 ,  A61F2230/0023 ,  A61F2230/0063 ,  A61F2230/0093 ,  A61F2240/001 ,  A61F2240/002 ,  A61F2250/0023 ,  A61L27/18 ,  A61L27/38 ,  B01D67/003 ,  B01D2325/02 ,  C08J9/26 ,  C08L67/04

摘要： Polymeric materials are used,to make a pliable, non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, allows vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix following implantation, and the injection of cells uniformly throughout the implanted matrix without damage to the cells or patient. The introduced cells attach to the connective tissue within the matrix and are fed by the blood vessels. The preferred material for forming the matrix or support structure is a biocompatible synthetic polymer which degrades in a controlled manner by hydrolysis into harmless metabolites, for example, polyglycolic acid, polylactic acid, polyorthoester, polyanhydride, or copolymers thereof. The rate of tissue ingrowth increases as the porosity and/or the pore size of the implanted devices increases. The time required for the tissue to fill the device depends on the polymer crystallinity and is less for amorphous polymers versus semicrystalline polymers. The vascularity of the advancing tissue is consistent with time and independent of the biomaterial composition and morphology.

摘要翻译： 使用聚合材料制成柔韧，无毒，可注射的多孔模板用于血管向内生长。 通常在约100和300微米之间的孔径允许血管和结缔组织在植入后约10至90％的基质向内生长，并且在整个植入的基质中均匀注射细胞而不损伤细胞或患者。 引入的细胞附着到基质内的结缔组织，并由血管进食。 用于形成基质或支撑结构的优选材料是生物相容的合成聚合物，其通过水解以受控的方式降解成无害的代谢物，例如聚乙醇酸，聚乳酸，聚原酸酯，聚酐或其共聚物。 随着植入装置的孔隙率和/或孔径增加，组织向内生长的速率增加。 组织填充装置所需的时间取决于聚合物的结晶度，对于无定形聚合物与半结晶聚合物相比较少。 前进组织的血管分布与时间一致，与生物材料组成和形态无关。

公开(公告)号：US06537567B1

公开(公告)日：2003-03-25

申请号：US09109427

申请日：1998-07-02

申请人： Laura E. Niklason ,  Jinming Gao ,  Robert S. Langer

发明人： Laura E. Niklason ,  Jinming Gao ,  Robert S. Langer

IPC分类号： A61F200

CPC分类号： A61L27/507 ,  C12M21/08 ,  C12M23/06 ,  C12M23/26 ,  C12M25/14 ,  C12M29/14 ,  C12M35/04 ,  C12N5/0068 ,  C12N5/0691 ,  C12N2500/20 ,  C12N2500/32 ,  C12N2503/04 ,  C12N2509/00 ,  C12N2533/40

摘要： Improved methods for the production of tissue-engineered constructs, including muscular tissue constructs such as vascular constructs, are disclosed. The methods include the use of improved substrates for cell growth, improved cell culture media for cell growth, and the use of distensible bodies to impart pulsatile stretching force to lumens of constructs during growth. Also disclosed are improved products and methods for making those products, including substrates and cell culture media, for tissue engineering and tissue culture generally. Improved muscular tissue constructs, including vascular constructs, are also disclosed, which may be used in medicine for the repair or replacement of damaged natural structures. In an embodiment, a muscular, tubular tissue-engineered construct is prepared having a wall of mammalian smooth muscle cells oriented circumferentially about a lumen of the construct at a cell density of at least 107 cells/cc.

摘要翻译： 公开了用于生产组织工程构建体（包括肌肉组织构建体如血管构建体）的改进方法。 所述方法包括使用用于细胞生长的改良底物，用于细胞生长的改进的细胞培养基，以及使用扩张体在生长过程中对构建体的内腔赋予脉动拉伸力。 还公开了通常用于组织工程和组织培养的用于制造包括底物和细胞培养基的那些产物的改进的产品和方法。 还公开了改进的肌肉组织构建体，包括血管构建体，其可用于医学中用于修复或替换受损的天然结构。 在一个实施方案中，制备肌肉，管状组织工程改造的构建体，其具有以至少107个细胞/ cc的细胞密度围绕构建体的内腔定向的哺乳动物平滑肌细胞壁。

公开(公告)号：US06399102B1

公开(公告)日：2002-06-04

申请号：US09562988

申请日：2000-05-01

申请人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdellaziz Ben-Jebria ,  Robert S. Langer

发明人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdellaziz Ben-Jebria ,  Robert S. Langer

IPC分类号： A61K914

CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/137

摘要： Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cm3 and a mass mean diameter between 5 &mgr;m and 30 &mgr;m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear &agr;-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.