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    Compounds having peptides conjugated to bone targeting moieties and methods of making and using thereof
    1.
    发明授权
    Compounds having peptides conjugated to bone targeting moieties and methods of making and using thereof 有权
    具有与骨靶向部分缀合的肽的化合物及其制备和使用方法

    公开(公告)号：US08772235B2

    公开(公告)日：2014-07-08

    申请号：US13501652

    申请日：2010-10-12

    Applicant: Michael R. Doschak ,  Krishna Hari Bhandari

    Inventor： Michael R. Doschak ,  Krishna Hari Bhandari

    IPC: A61K47/48 ,  A61K38/23 ,  A61P19/08

    CPC classification number: A61K47/48 ,  A61K38/23 ,  A61K47/50 ,  A61K47/548

    Abstract: Described herein are compositions having a peptide sequence that includes at least one bone targeting moiety, wherein the bone targeting moiety is bonded to the peptide sequence by a linker, wherein the peptide sequence is calcitonin, and wherein the composition is neutral or a pharmaceutically acceptable salt or ester thereof. In one aspect, calcitonin inhibits or slows osteoclast mediated resorptive bone loss. The compounds described herein can be used in a number of therapeutic applications including treating or preventing conditions associated with bone loss, which include, but are not limited to, osteoporosis, Paget's disease, osteolytic tumors, Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Osteoarthritis, osteopenia, and hypercalcemia. Also described herein are the methods of making these compositions that prevent or treat conditions associated with bone loss and methods of preventing bone fractures.

    Abstract translation: 本文描述的是具有肽序列的组合物，其包含至少一个骨靶向部分，其中骨靶向部分通过接头与肽序列连接，其中肽序列是降钙素，并且其中所述组合物是中性或药学上可接受的盐 或其酯。 一方面，降钙素抑制或减缓破骨细胞介导的吸收性骨丢失。 本文所述的化合物可用于许多治疗应用，包括治疗或预防与骨丢失相关的病症，其包括但不限于骨质疏松症，佩吉特氏病，溶骨性肿瘤，类风湿关节炎，银屑病关节炎，强直性脊柱炎，骨关节炎 ，骨质减少和高钙血症。 本文还描述了制备这些组合物以防止或治疗与骨丢失相关的病症的方法以及预防骨折的方法。

    Interaction of thermal hysteresis proteins with cells and cell membranes and associated applications
    4.
    发明授权
    Interaction of thermal hysteresis proteins with cells and cell membranes and associated applications 失效
    热滞后蛋白与细胞和细胞膜的相互作用及相关应用

    公开(公告)号：US5358931A

    公开(公告)日：1994-10-25

    申请号：US4919

    申请日：1993-01-15

    Applicant: Boris Rubinsky ,  Arthur L. Devries ,  Amir Arav

    Inventor： Boris Rubinsky ,  Arthur L. Devries ,  Amir Arav

    IPC: A01N1/02 ,  A61K47/48 ,  C07K14/46 ,  A61K37/00 ,  A61K37/10

    CPC classification number: A01N1/02 ,  A01N1/0221 ,  A61K47/48 ,  C07K14/461

    Abstract: A newly discovered property of thermal hysteresis proteins is the interaction of these proteins with cell membranes and thus with cells themselves, protecting cells and their membranes from damage which they would otherwise suffer upon exposure to non-physiological conditions such as temperature abnormalities, including both hyperthermic, hypothermic and sub-freezing temperatures. Improved rates of cell viability are observed over a wide range of conditions which do not involve ice formation, including temperatures above the freezing range as well as temperatures below the freezing range but in vitrification conditions. Heretofore the only known property of these proteins was their ability to interact with ice crystals. In conditions in which ice crystals are formed, it is further discovered that use of the proteins with human cells at the concentrations in which they naturally occur in the source organisms results in aggravating the injury to the cells rather than reducing it, but that the injury is lessened, and the survival rate improved, by using low concentrations. The proteins thus offer benefits in the preservation and improved viability of cell suspensions, tissues and whole organs. The proteins are further discovered to have the ability to block ion channels in mammalian cell membranes, thereby providing a further utility in the treatment of disease conditions.

    Abstract translation: 新发现的热滞后蛋白质是这些蛋白质与细胞膜的相互作用，因此与细胞本身相互作用，保护细胞和它们的膜免受其它暴露于非生理条件（如温度异常） ，低温和低温温度。 在不涉及冰形成的宽范围条件下观察到细胞存活率的改善，包括高于冷冻范围的温度以及低于冰点范围的温度，但在玻璃化条件下。 迄今为止，这些蛋白质唯一已知的性质是它们与冰晶相互作用的能力。 在形成冰晶的条件下，进一步发现，使用蛋白质与人类细胞以其天然存在于源生物体中的浓度导致加重对细胞的损伤而不是降低细胞损伤，但是损伤 通过使用低浓度降低生存率。 因此，蛋白质在细胞悬浮液，组织和整个器官的保存和改善的活力方面提供益处。 进一步发现蛋白质具有阻止哺乳动物细胞膜中的离子通道的能力，从而提供治疗疾病状况的另外的效用。

    Comb copolymers for regulating cell-surface interactions
    5.
    发明授权
    Comb copolymers for regulating cell-surface interactions 有权
    用于调节细胞表面相互作用的梳状共聚物

    公开(公告)号：US06399700B2

    公开(公告)日：2002-06-04

    申请号：US09817887

    申请日：2001-03-26

    Applicant: Anne M. Mayes ,  Linda G. Griffith ,  Darrell J. Irvine ,  Pallab Banerjee ,  Terry D. Johnson

    Inventor： Anne M. Mayes ,  Linda G. Griffith ,  Darrell J. Irvine ,  Pallab Banerjee ,  Terry D. Johnson

    IPC: C08J524

    CPC classification number: A61K47/48 ,  A61K47/50 ,  A61K47/56 ,  A61K47/641 ,  C08G81/00 ,  C08G81/024 ,  C08J5/24

    Abstract: Synthetic comb copolymers which elicit controlled cellular response, methods of applying these polymers to various surfaces, and methods of using the polymers for modifying biomaterial surfaces, in tissue engineering applications and as drug delivery devices are provided. The comb copolymers are comprised of hydrophobic polymer backbones and hydrophilic, non-cell binding side chains which can be end-capped with cell-signaling ligands that guide cellular response. By mixing non-cell binding combs with ligand-bearing combs, the surface concentration and spatial distribution of one or more types of ligands, including adhesion peptides and growth factors, can be tuned on a surface to achieve desired cellular response. In one embodiment, the combs are used as stabilizing agents for dispersion polymerization of latexes. The comb-stabilized latexes can be applied to substrates by standard coating operations to create a bioregulating surface, or used as drug delivery agents. In another embodiment, the combs can be blended in small quantities to a hydrophobic matrix polymer and processed to affect the surface segregation of the comb. The comb copolymers are formed in one embodiment by providing a biodegradable polyester backbone that includes reactive groups, and reacting the reactive groups in the backbone with reactive chain ends on a low molecular weight hydrophilic polymer. In another embodiment, non-biodegradable comb copolymers are formed by free radical synthesis of a hydrophobic monomer and a hydrophilic macromonomer. In all of the above embodiments, a portion of the hydrophilic polymer side chains can be covalently coupled to cell-signaling ligands such as adhesion peptides or growth factors to control cellular response.

    Abstract translation: 提供引起受控细胞反应的合成梳状共聚物，将这些聚合物应用于各种表面的方法，以及使用聚合物改性生物材料表面的方法，在组织工程应用中以及作为药物递送装置。 梳状共聚物由疏水性聚合物主链和亲水性非细胞结合侧链组成，其可以用引导细胞反应的细胞信号传导配体封端。 通过将非细胞结合梳与含配体的梳子混合，可以在表面上调节一种或多种类型的配体（包括粘附肽和生长因子）的表面浓度和空间分布，以实现所需的细胞反应。 在一个实施方案中，梳子用作胶乳分散聚合的稳定剂。 梳状稳定的胶乳可以通过标准涂布操作施加到基底上以产生生物调节表面，或用作药物递送剂。 在另一个实施方案中，梳子可以少量混合到疏水性基质聚合物中并进行处理以影响梳子的表面分离。 梳状共聚物在一个实施方案中通过提供包含反应性基团的可生物降解的聚酯主链，并使主链中的反应性基团与低分子量亲水聚合物上的反应性链端端反应形成。 在另一个实施方案中，通过自由基合成疏水性单体和亲水性大分子单体形成不可生物降解的梳状共聚物。 在所有上述实施方案中，一部分亲水性聚合物侧链可共价偶联至细胞信号传导配体如粘附肽或生长因子以控制细胞反应。

    Comb copolymers for regulating cell-surface interactions
    6.
    发明授权
    Comb copolymers for regulating cell-surface interactions 有权
    用于调节细胞表面相互作用的梳状共聚物

    公开(公告)号：US06207749B1

    公开(公告)日：2001-03-27

    申请号：US09634095

    申请日：2000-08-08

    Applicant: Anne M. Mayes ,  Linda G. Griffith ,  Darrell J. Irvine ,  Pallab Banerjee ,  Terry D. Johnson

    Inventor： Anne M. Mayes ,  Linda G. Griffith ,  Darrell J. Irvine ,  Pallab Banerjee ,  Terry D. Johnson

    IPC: C08J524

    CPC classification number: A61K47/48 ,  A61K47/50 ,  A61K47/56 ,  A61K47/641 ,  C08G81/00 ,  C08G81/024 ,  C08J5/24

    Abstract: Synthetic comb copolymers which elicit controlled cellular response, methods of applying these polymers to various surfaces, and methods of using the polymers for modifying biomaterial surfaces, in tissue engineering applications and as drug delivery devices are provided. The comb copolymers are comprised of hydrophobic polymer backbones and hydrophilic, non-cell binding side chains which can be end-capped with cell-signaling ligands that guide cellular response. By mixing non-cell binding combs with ligand-bearing combs, the surface concentration and spatial distribution of one or more types of ligands, including adhesion peptides and growth factors, can be tuned on a surface to achieve desired cellular response. In one embodiment, the combs are used as stabilizing agents for dispersion polymerization of latexes. The comb-stabilized latexes can be applied to substrates by standard coating operations to create a bioregulating surface, or used as drug delivery agents. In another embodiment, the combs can be blended in small quantities to a hydrophobic matrix polymer and processed to affect the surface segregation of the comb. The comb copolymers are formed in one embodiment by providing a biodegradable polyester backbone that includes reactive groups, and reacting the reactive groups in the backbone with reactive chain ends on a low molecular weight hydrophilic polymer. In another embodiment, non-biodegradable comb copolymers are formed by free radical synthesis of a hydrophobic monomer and a hydrophilic macromonomer. In all of the above embodiments, a portion of the hydrophilic polymer side chains can be covalently coupled to cell-signaling ligands such as adhesion peptides or growth factors to control cellular response.

    Abstract translation: 提供引起受控细胞反应的合成梳状共聚物，将这些聚合物应用于各种表面的方法，以及使用聚合物改性生物材料表面的方法，在组织工程应用中以及作为药物递送装置。 梳状共聚物由疏水性聚合物主链和亲水性非细胞结合侧链组成，其可以用引导细胞反应的细胞信号传导配体封端。 通过将非细胞结合梳与含配体的梳子混合，可以在表面上调节一种或多种类型的配体（包括粘附肽和生长因子）的表面浓度和空间分布，以实现所需的细胞反应。 在一个实施方案中，梳子用作胶乳分散聚合的稳定剂。 梳状稳定的胶乳可以通过标准涂布操作施加到基底上以产生生物调节表面，或用作药物递送剂。 在另一个实施方案中，梳子可以少量混合到疏水性基质聚合物中并进行处理以影响梳子的表面分离。 梳状共聚物在一个实施方案中通过提供包含反应性基团的可生物降解的聚酯主链，并使主链中的反应性基团与低分子量亲水聚合物上的反应性链端端反应形成。 在另一个实施方案中，通过自由基合成疏水性单体和亲水性大分子单体形成不可生物降解的梳状共聚物。 在所有上述实施方案中，一部分亲水性聚合物侧链可共价偶联至细胞信号传导配体如粘附肽或生长因子以控制细胞反应。

    Bifunctional chelating agents
    10.
    发明授权
    Bifunctional chelating agents 失效
    双功能螯合剂

    公开(公告)号：US5227474A

    公开(公告)日：1993-07-13

    申请号：US706149

    申请日：1991-05-28

    Applicant: David K. Johnson ,  Steven J. Kline

    Inventor： David K. Johnson ,  Steven J. Kline

    IPC: A61K47/48 ,  C07C275/42 ,  C07C335/22

    CPC classification number: A61K47/48 ,  C07C275/42 ,  C07C335/22

    Abstract: The present invention provides bifunctional chelating agents comprising a unique substrate reactive moiety incorporated into a carboxymethyl arm of a polyaminopolycarboxylate chelating framework capable of forming stable complexes with metal ions.

    Abstract translation: 本发明提供了双功能螯合剂，其包含结合到能与金属离子形成稳定的络合物的聚氨基多羧酸盐螯合骨架的羧甲基臂中的独特的底物反应性部分。

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