利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

107 条记录 (耗时 0.05 秒)

    Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides
    61.
    发明授权
    Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides 失效
    用于组织工程的酶介导的纤维蛋白修饰：具有肽的纤维蛋白制剂

    公开(公告)号：US07241730B2

    公开(公告)日：2007-07-10

    申请号：US10106804

    申请日：2002-03-25

    申请人： Jeffrey A. Hubbell ,  Jason C. Schense ,  Shelly E. Sakiyama

    发明人： Jeffrey A. Hubbell ,  Jason C. Schense ,  Shelly E. Sakiyama

    IPC分类号： A01N37/18

    CPC分类号： C07K14/75 ,  A61L26/0042 ,  C12N5/0068 ,  C12N5/0619 ,  C12N2501/91 ,  C12N2533/56

    摘要： Heparin-binding regions of several proteins, such as neural cell adhesion molecule, fibronectin, laminin, midkine, and anti-thrombin III have been shown to promote neurite extension on two-dimensional surfaces. The effect of heparin-binding peptides on neurite extension through three-dimensional matrices was investigated by culturing embryonic chick dorsal root ganglia (DRG) within fibrin gels containing chemically attached heparin-binding peptide (HBP). The length of neurites within fibrin gels containing cross-linked HBP was increased by more than 70% over extension through fibrin gels containing no peptide. The HBP sequence of antithrombin III was incorporated into the fibrin gel as the C-terminal domain of a bidomian, chimeric peptide; the N-terminal second domain of this peptide contained the ∀2-plasmin inhibitor substrate for Factor XIIIa. Factor XIIIa, a transglutaminase, was used to chemically attach the HBP-containing chimeric peptide to the fibrin gels during polymerization. The amount of HBP cross-linked into the fibrin gels was determined, after degradation by plasmin using gel permeation chromatography, to be approximately 8 moles of peptide per mole fibrinogen. A peptide (HBP), where the cross-linking glutamine was replaced with glycine, showed no increase in extension in comparison with fibrin gels. The additional of heparin to the gel percursors resulted in no increase in neurite extension in comparison with fibrin gels. HBPs promote neurite extension by binding to cell surface proteoglycans on the DRG.

    摘要翻译： 几种蛋白质的肝素结合区域，例如神经细胞粘附分子，纤连蛋白，层粘连蛋白，中期因子和抗凝血酶III已被证明可促进二维表面的神经突延伸。 通过在包含化学连接的肝素结合肽（HBP）的纤维蛋白凝胶内培养胚胎小鸡背根神经节（DRG），研究肝素结合肽对通过三维基质的神经突延伸的作用。 含有交联HBP的纤维蛋白凝胶中的神经突的长度比通过不含肽的纤维蛋白凝胶延长超过70％。 抗凝血酶III的HBP序列被掺入纤维蛋白凝胶中，作为bid族嵌合肽的C-末端结构域; 该肽的N末端第二结构域含有因子XIIIa的∀2-纤溶酶抑制剂底物。 在聚合期间，使用因子XIIIa，转谷氨酰胺酶将含HBP的嵌合肽化学连接到纤维蛋白凝胶上。 在使用凝胶渗透色谱法的纤溶酶降解之后，测定交联到纤维蛋白凝胶中的HBP的量为每摩尔纤维蛋白原约8摩尔肽。 交联谷氨酰胺被甘氨酸取代的肽（HBP）与纤维蛋白凝胶相比显示延长不增加。 与纤维蛋白凝胶相比，附加的凝胶过程中的肝素导致神经突延伸不增加。 HBP通过与DRG上的细胞表面蛋白聚糖结合来促进神经突延伸。

    Multifunctional polymeric tissue coatings
    64.
    发明授权
    Multifunctional polymeric tissue coatings 失效
    多功能聚合物组织涂层

    公开(公告)号：US06743521B2

    公开(公告)日：2004-06-01

    申请号：US09403428

    申请日：2000-01-06

    申请人： Jeffrey A. Hubbell ,  Donald L. Elbert ,  Curtis B. Herbert

    发明人： Jeffrey A. Hubbell ,  Donald L. Elbert ,  Curtis B. Herbert

    IPC分类号： B32B1800

    CPC分类号： C08G81/00 ,  A61K9/10 ,  A61K9/5031 ,  A61K9/5073 ,  A61K31/00 ,  A61K47/34 ,  A61L27/34 ,  A61L31/10 ,  B33Y80/00 ,  Y10T428/31504 ,  Y10T428/31678 ,  Y10T428/31725 ,  Y10T428/31855 ,  Y10T428/31971

    摘要： Compositions for coating biological and non-biological surfaces, which minimize or prevent cell-cell contact and tissue adhesion, and methods of preparation and use thereof, are disclosed. Embodiments include polyethylene glycol/polylysine (PEG/PLL) block or comb-type copolymers with high molecular weight PLL (greater than 1000, more preferably greater than 100,000); PEG/PLL copolymers in which the PLL is a dendrimer which is attached to one end of the PEG; and multilayer compositions including alternating layers of polycationic and polyanionic materials. The multi-layer polymeric material is formed by the ionic interactions of a polycation and a polyanion. The molecular weights of the individual materials are selected such that the PEG portion of the copolymer inhibits cellular interactions, and the PLL portion adheres well to tissues. The compositions and methods are useful, for example, in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells. The compositions and methods are also useful for coating non-biological surfaces such as metallic surfaces.

    摘要翻译： 公开了用于涂覆生物和非生物表面的组合物，其最小化或防止细胞 - 细胞接触和组织粘附，以及其制备和使用方法。 实施方案包括具有高分子量PLL（大于1000，更优选大于100,000）的聚乙二醇/聚赖氨酸（PEG / PLL）嵌段或梳型共聚物; PEG / PLL共聚物，其中PLL是连接到PEG的一端的树枝状大分子; 以及包括聚阳离子和聚阴离子材料的交替层的多层组合物。 多层聚合物材料通过聚阳离子和聚阴离子的离子相互作用形成。 选择各种材料的分子量使得共聚物的PEG部分抑制细胞相互作用，并且PLL部分粘附到组织上。 组合物和方法可用于例如抑制手术后粘连的形成，保护受损的血管免受血栓形成和再狭窄，以及降低附着依赖性肿瘤细胞的转移程度。 组合物和方法也可用于涂覆非生物表面如金属表面。

    Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers
    65.
    发明授权
    Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers 失效
    用于稳定包封在可生物降解的控释聚合物中的生物活性剂的方法

    公开(公告)号：US06743446B2

    公开(公告)日：2004-06-01

    申请号：US09738961

    申请日：2000-12-15

    申请人： Steven P. Schwendeman ,  Gaozhong Zhu ,  Hanne Bentz ,  Jeffrey A. Hubbell ,  Wenlei Jiang ,  Anna Shenderova ,  Jichao Kang

    发明人： Steven P. Schwendeman ,  Gaozhong Zhu ,  Hanne Bentz ,  Jeffrey A. Hubbell ,  Wenlei Jiang ,  Anna Shenderova ,  Jichao Kang

    IPC分类号： A61K914

    CPC分类号： A61K9/1647 ,  A61K9/0019 ,  A61K47/02

    摘要： Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing a PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.

    摘要翻译： 提供了用于减少或抑制在可生物降解的聚合物递送系统中的水溶性生物活性剂的不可逆失活的方法，其被设计为在长时间内释放这些试剂，例如PLGA递送系统。 该方法包括制备PLGA递送系统，其微生物即活性剂所在的孔在生物降解过程中均匀或均匀地保持在3至9之间，优选4至8之间，更优选5至7.5的pH。 根据输送系统的尺寸和聚合物的初始体积渗透性，该结果通过（a）将水溶性载体引入输送系统来实现，（b）将选择的碱性添加剂（或抗酸剂）掺入 递送系统，（c）将水溶性载体和选择性碱性添加剂并入输送系统中，（d）添加成孔分子，以将低分子量单体和低聚物的释放速率提高到递送系统中（ e）使用具有降低的乙交酯含量的PLGA聚合物，即具有100％至75％丙交酯和0至25％乙交酯的PLGA）（f）使用产生更广泛孔隙网络的微胶囊化方法，例如 油包水乳液 - 溶剂萃取相对于水包油型水溶剂蒸发法，和（g）它们的组合。

    Gels and multilayer surface structures from boronic acid containing polymers
    66.
    发明授权
    Gels and multilayer surface structures from boronic acid containing polymers 有权

    公开(公告)号：US06652902B2

    公开(公告)日：2003-11-25

    申请号：US10035625

    申请日：2001-12-28

    申请人： Jeffrey A. Hubbell ,  Donald L. Elbert ,  Natalie D. Winblade

    发明人： Jeffrey A. Hubbell ,  Donald L. Elbert ,  Natalie D. Winblade

    IPC分类号： B05D300

    CPC分类号： A61L31/10 ,  A61L27/34 ,  A61L29/085 ,  C08L71/02

    摘要： Boronic acid containing polymers are used to form bioinert gels and multilayer surface structures. These polymers form crosslinked hydrogels, which are highly swollen in water. The crosslinking can either be chemical or physical. Water soluble polymers containing boronic acid groups, such as phenylboronic acid (PBA), can be physically crosslinked by mixing the polymers in water with other polymers containing hydroxyls or carboxylic acids. Alternatively, surfaces can be treated by stepwise incubation with a solution of the boronic acid containing polymer, followed by incubation with a solution of a diol or carboxylic acid containing polymer. Many successive layers can be generated, increasing the thickness of the formed structure at each step. The bioinert gel or surface coating can be used for passivating the surfaces of medical implants (especially those based on transplanted tissue), or for passivating the surfaces of tissues in situ, decreasing the incidence or severity of such pathologic conditions as the formation of post-surgical adhesions, and thrombosis following angioplasty.

    Gels and multilayer surface structures from boronic acid containing polymers
    67.
    发明授权
    Gels and multilayer surface structures from boronic acid containing polymers 有权
    含有硼酸的聚合物的凝胶和多层表面结构

    公开(公告)号：US06350527B1

    公开(公告)日：2002-02-26

    申请号：US09384888

    申请日：1999-08-27

    申请人： Jeffrey A. Hubbell ,  Donald L. Elbert ,  Natalie D. Winblade

    发明人： Jeffrey A. Hubbell ,  Donald L. Elbert ,  Natalie D. Winblade

    IPC分类号： B32B904

    CPC分类号： A61L31/10 ,  A61L27/34 ,  A61L29/085 ,  C08L71/02

    摘要： Boronic acid containing polymers are used to form bioinert gels and multilayer surface structures. These polymers form crosslinked hydrogels, which are highly swollen in water. The crosslinking can either be chemical or physical. Water soluble polymers containing boronic acid groups, such as phenylboronic acid (PBA), can be physically crosslinked by mixing the polymers in water with other polymers containing hydroxyls or carboxylic acids. Alternatively, surfaces can be treated by stepwise incubation with a solution of the boronic acid containing polymer, followed by incubation with a solution of a diol or carboxylic acid containing polymer. Many successive layers can be generated, increasing the thickness of the formed structure at each step. The bioinert gel or surface coating can be used for passivating the surfaces of medical implants (especially those based on transplanted tissue), or for passivating the surfaces of tissues in situ.

    摘要翻译： 含硼酸的聚合物用于形成生物凝胶和多层表面结构。 这些聚合物形成在水中高度溶胀的交联水凝胶。 交联可以是化学或物理的。 含有硼酸基团的水溶性聚合物如苯基硼酸（PBA）可通过将水中的聚合物与含有羟基或羧酸的其它聚合物混合而物理交联。 或者，可以通过与含硼酸的聚合物的溶液逐步温育，然后与含二醇或含羧酸的聚合物的溶液温育来处理表面。 可以产生许多连续的层，从而在每个步骤增加形成的结构的厚度。 生物测定凝胶或表面涂层可用于钝化医疗植入物（特别是基于移植组织的植入物）表面，或用于钝化组织表面的原位。