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.

公开(公告)号：US06326020B1

公开(公告)日：2001-12-04

申请号：US09079622

申请日：1998-05-15

申请人： Daniel S. Kohane ,  Charles B. Berde ,  Gary Strichartz ,  Robert S. Langer

发明人： Daniel S. Kohane ,  Charles B. Berde ,  Gary Strichartz ,  Robert S. Langer

IPC分类号： A61F200

摘要： Combinations of naturally occurring site 1 sodium channel blockers, such as tetrodotoxin (TTX), saxitoxin (STX), decarbamoyl saxitoxin, and neosaxitoxin (referred to jointly herein as “toxins”), with other agents, have been developed to give long duration block with improved features, including safety and specificity. In one embodiment, duration of block is greatly prolonged by combining a toxin with a local anesthetic, vasoconstrictor, glucocorticoid, and/or adrenergic drugs, both alpha agonists (epinephrine, phenylephrine), beta-blockers (propranalol), and mixed central-peripheral alpha-2 agonists (clonidine), or other agents. In another embodiment, the duration of nerve block from toxin can be greatly enhanced by the inclusion of amphiphilic or lipophilic solvents. In still another embodiment, the effectiveness of these compositions is enhanced by microencapsulation within polymeric carriers, preferably biodegradable synthetic polymeric carriers. Modality specific nerve block can be obtained using combinations of toxin with vanilloids.

摘要翻译： 已经开发出天然存在的1位钠通道阻断剂如河豚毒素（TTX），沙毒素（STX），脱氨甲酰沙司苏辛和新西沙毒素（本文共同称为“毒素”）与其他药物的组合，以产生长期阻滞 具有改进的特征，包括安全性和特异性。 在一个实施方案中，通过将毒素与局部麻醉剂，血管收缩剂，糖皮质激素和/或肾上腺素能药物α激动剂（肾上腺素，去氧肾上腺素），β-阻滞剂（propranalol）和混合的中枢外周 α-2激动剂（可乐定）或其它药剂。 在另一个实施方案中，通过包含两亲或亲脂性溶剂可以大大增强来自毒素的神经阻滞的持续时间。 在另一个实施方案中，这些组合物的有效性通过聚合物载体（优选可生物降解的合成聚合物载体）内的微囊化来增强。 可以使用毒素与香草素的组合获得形态特异性神经阻滞。

公开(公告)号：US06262183B1

公开(公告)日：2001-07-17

申请号：US08219160

申请日：1994-03-28

申请人： Abraham J. Domb ,  Robert S. Langer ,  Ernest G. Cravalho ,  Gershon Golomb ,  Edith Mathiowitz ,  Cato T. Laurencin

发明人： Abraham J. Domb ,  Robert S. Langer ,  Ernest G. Cravalho ,  Gershon Golomb ,  Edith Mathiowitz ,  Cato T. Laurencin

IPC分类号： C08F2056

CPC分类号： C08F8/32 ,  C08F2800/10 ,  C08F8/42 ,  C08F220/56

摘要： Hydroxamic acid polymers which are comprised of hydroxamic groups and carboxylic acid groups wherein the carboxylic acid groups constitute less than about 3% of the functional groups. The polymers hereof are also especially useful in biomedical applications because, for example, the low concentration of carboxylic acid groups decreases the incidence of bioincompatibility. Additionally, the polymers exhibit anticoagulant activity, urease inhibition activity, metal chelating activity and ion exchange activity.

摘要翻译： 由异羟肟基和羧酸基组成的羟肟酸聚合物，其中羧酸基构成少于官能团的约3％。这里的聚合物在生物医学应用中也特别有用，因为例如低浓度的羧酸 组降低生物相容性的发生率。 另外，聚合物显示抗凝血活性，脲酶抑制活性，金属螯合活性和离子交换活性。

公开(公告)号：US06174952B1

公开(公告)日：2001-01-16

申请号：US09156720

申请日：1998-09-18

申请人： Ihab M. Hekal ,  Robert S. Langer ,  Alexander M. Klibanov ,  Edith Mathiowitz

发明人： Ihab M. Hekal ,  Robert S. Langer ,  Alexander M. Klibanov ,  Edith Mathiowitz

IPC分类号： C08J900

CPC分类号： C08L23/02 ,  B01J20/28014 ,  B01J20/28033 ,  B01J20/28042 ,  B29C45/16 ,  B65D81/264 ,  B65D81/266 ,  C08J9/26 ,  C08L23/0861 ,  C08L23/10 ,  C08L29/04 ,  C08L69/00 ,  C08L71/02 ,  C08L77/00 ,  C08L101/00 ,  F26B21/083 ,  Y10S521/905 ,  C08L2666/02 ,  C08L2666/14 ,  C08L2666/04 ,  C08L2666/22 ,  C08L29/00 ,  C08L71/00

摘要： The present invention includes processes and resulting structures for producing a modified polymer having interconnecting channels. The interconnecting channels act as controlled transmission passages through the polymer. A hydrophilic agent is blended into the polymer so that it is distributed within the polymer. In one embodiment, a water-absorbing material is blended into the polymer so that the water-absorbing material is distributed within the product. The product is solidified so that the hydrophilic agent forms passages in the product through which a desired composition is communicable to the water-absorbing material that is entrained within the product. The solidified product may be used to form a desired shaped article such as plug type inserts and liners for closed containers, or it may be formed into a film, sheet, bead or pellet.

摘要翻译： 本发明包括用于生产具有互连通道的改性聚合物的方法和所得结构。 互连通道充当通过聚合物的受控传输通道。 将亲水剂混合到聚合物中，使其分散在聚合物内。 在一个实施方案中，将吸水材料混合到聚合物中，使得吸水材料分布在产品内。 产品被固化，使得亲水剂在产品中形成通道，通过该通道，期望的组合物可通过其吸入产品中的吸水材料连通。 固化产品可以用于形成所需的成型制品，例如用于密封容器的塞子型插入件和衬垫，或者可以形成为膜，片，珠粒或丸粒。

公开(公告)号：US6060082A

公开(公告)日：2000-05-09

申请号：US844138

申请日：1997-04-18

申请人： Hongming Chen ,  Robert S. Langer

发明人： Hongming Chen ,  Robert S. Langer

IPC分类号： A61K9/127 ,  A61K38/28 ,  A61K39/00 ,  A61K39/05 ,  A61K48/00

CPC分类号： A61K39/05 ,  A61K38/28 ,  A61K39/00 ,  A61K48/00 ,  A61K9/1273 ,  A61K2039/541 ,  A61K2039/55555 ,  Y10S436/829 ,  Y10T428/2984

摘要： The present invention relates to targeted polymerized liposomes for oral and/or mucosal delivery of vaccines, allergens and therapeutics. In particular, the present invention relates to polymerized liposomes which have been modified on their surface to contain a molecule or ligand which targets the polymerized liposome to a specific site or cell type. More particularly, the invention relates to the use of polymerized liposomes modified to contain a carbohydrate or lectin on their surface.