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    Method of making hydroxamic acid polymers from primary amide polymers
    2.
    发明授权
    Method of making hydroxamic acid polymers from primary amide polymers 失效
    由一级酰胺聚合物制备异羟肟酸聚合物的方法

    公开(公告)号：US5128420A

    公开(公告)日：1992-07-07

    申请号：US283594

    申请日：1988-12-13

    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： C08F8/32

    CPC分类号： C08F8/32 ,  C08F2800/10 ,  C08F2810/20

    摘要： A method for preparing hydroxamic acid polymers from primary amide polymers wherein polyvinyl monomers such as polyacrylamide are reacted with hydroxyl amine in aqueous solution at room temperature. The low reaction temperature is crucial to producing a high yield (70%) of polymer with hydroxamic acid groups and having a low carboxylic acid content (less than 15%, preferably less than 3%). The polymers display high metal affinity over a broad pH range.The polymers are particularly useful for biomedical applications due to the low carboxylic acid content and for the removal and purification of metals due to the high binding constants and rapid reaction rates.

    摘要翻译： 由聚酰胺聚合物制备异羟肟酸聚合物的方法，其中聚乙烯基单体例如聚丙烯酰胺在室温下与羟胺在水溶液中反应。 低反应温度对于用异羟肟酸基团产生高产率（70％）的聚合物和低羧酸含量（小于15％，优选小于3％）是至关重要的。 聚合物在宽pH范围内显示出高的金属亲和力。 由于高的结合常数和快速的反应速率，由于羧酸含量低以及金属的去除和纯化，聚合物特别适用于生物医学应用。

    PH SENSITIVE BIODEGRADABLE POLYMERIC PARTICLES FOR DRUG DELIVERY
    3.
    发明申请
    PH SENSITIVE BIODEGRADABLE POLYMERIC PARTICLES FOR DRUG DELIVERY 有权
    PH敏感的生物可降解聚合物颗粒用于药物递送

    公开(公告)号：US20110065807A1

    公开(公告)日：2011-03-17

    申请号：US12762348

    申请日：2010-04-18

    申请人： Aleksandar Filip Radovic-Moreno ,  Weiwei Gao ,  Archana Swami ,  Gershon Golomb ,  Robert S. Langer ,  Omid C. Farokhzad

    发明人： Aleksandar Filip Radovic-Moreno ,  Weiwei Gao ,  Archana Swami ,  Gershon Golomb ,  Robert S. Langer ,  Omid C. Farokhzad

    IPC分类号： A61K47/30 ,  G01N21/76

    CPC分类号： A61K9/51 ,  A61K48/0008 ,  C12N15/111 ,  C12N15/115 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/16 ,  C12N2320/32

    摘要： The present invention generally relates to polymers and particles, such as nanoparticles. The particles and polymers generally include one or more buffering components. Additionally, the particles and polymers may include two or more components that impart useful properties (functionalities). The particles and polymers, for example, may include a buffering component and a degradable component. As described herein, the particles and polymers may also include a hydrophilic component and/or a cleavable bond component. The particles and polymers described herein have been found to be particularly effective when used for delivery of one or more agents, such as one or more pharmaceutical agents. Other aspects of the invention are directed to methods of using or administering such particles or polymers, kits involving such particles or polymers, and the like. The present invention also relates to particles containing a cleavable bond component and one or more fluorescence resonance energy transfer (FRET) pairs as well as methods of detecting the cleavage of the cleavable bond component of such particles.

    摘要翻译： 本发明一般涉及聚合物和颗粒，例如纳米颗粒。 颗粒和聚合物通常包括一种或多种缓冲组分。 此外，颗粒和聚合物可以包括赋予有用性质（功能）的两种或更多种组分。 颗粒和聚合物例如可以包括缓冲组分和可降解组分。 如本文所述，颗粒和聚合物还可以包括亲水组分和/或可裂解键组分。 已经发现本文所述的颗粒和聚合物在用于递送一种或多种试剂如一种或多种药剂时是特别有效的。 本发明的其它方面涉及使用或施用此类颗粒或聚合物的方法，涉及这种颗粒或聚合物的试剂等。 本发明还涉及含有可切割键组分和一种或多种荧光共振能量转移（FRET）对的颗粒以及检测这些颗粒的可裂解键组分的切割的方法。

    PH sensitive biodegradable polymeric particles for drug delivery
    4.
    发明授权
    PH sensitive biodegradable polymeric particles for drug delivery 有权
    PH敏感的生物可降解聚合物颗粒用于药物递送

    公开(公告)号：US09532956B2

    公开(公告)日：2017-01-03

    申请号：US12762348

    申请日：2010-04-18

    申请人： Aleksandar Filip Radovic-Moreno ,  Weiwei Gao ,  Archana Swami ,  Gershon Golomb ,  Robert S. Langer ,  Omid C. Farokhzad

    发明人： Aleksandar Filip Radovic-Moreno ,  Weiwei Gao ,  Archana Swami ,  Gershon Golomb ,  Robert S. Langer ,  Omid C. Farokhzad

    IPC分类号： A61K47/30 ,  G01N21/76 ,  A61K9/51 ,  A61K48/00 ,  C12N15/11 ,  C12N15/115

    CPC分类号： A61K9/51 ,  A61K48/0008 ,  C12N15/111 ,  C12N15/115 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/16 ,  C12N2320/32

    摘要： The present invention generally relates to polymers and particles, such as nanoparticles. The particles and polymers generally include one or more buffering components. Additionally, the particles and polymers may include two or more components that impart useful properties (functionalities). The particles and polymers, for example, may include a buffering component and a degradable component. As described herein, the particles and polymers may also include a hydrophilic component and/or a cleavable bond component. The particles and polymers described herein have been found to be particularly effective when used for delivery of one or more agents, such as one or more pharmaceutical agents. Other aspects of the invention are directed to methods of using or administering such particles or polymers, kits involving such particles or polymers, and the like. The present invention also relates to particles containing a cleavable bond component and one or more fluorescence resonance energy transfer (FRET) pairs as well as methods of detecting the cleavage of the cleavable bond component of such particles.

    摘要翻译： 本发明一般涉及聚合物和颗粒，例如纳米颗粒。 颗粒和聚合物通常包括一种或多种缓冲组分。 此外，颗粒和聚合物可以包括赋予有用性质（功能）的两种或更多种组分。 颗粒和聚合物例如可以包括缓冲组分和可降解组分。 如本文所述，颗粒和聚合物还可以包括亲水组分和/或可裂解键组分。 已经发现本文所述的颗粒和聚合物在用于递送一种或多种试剂如一种或多种药剂时是特别有效的。 本发明的其它方面涉及使用或施用此类颗粒或聚合物的方法，涉及这种颗粒或聚合物的试剂等。 本发明还涉及含有可切割键组分和一种或多种荧光共振能量转移（FRET）对的颗粒以及检测这些颗粒的可裂解键组分的切割的方法。

    Method of inhibiting restenosis using bisphosphonates
    5.
    发明申请
    Method of inhibiting restenosis using bisphosphonates 审中-公开
    使用双膦酸盐抑制再狭窄的方法

    公开(公告)号：US20070166385A1

    公开(公告)日：2007-07-19

    申请号：US11296153

    申请日：2005-12-06

    申请人： Gershon Golomb ,  Haim Danenberg

    发明人： Gershon Golomb ,  Haim Danenberg

    IPC分类号： A61K31/675 ,  A61K31/66 ,  A61K9/14

    CPC分类号： A61K9/5153 ,  A61K9/127 ,  A61K31/00 ,  A61K31/66 ,  A61K31/663 ,  A61K31/675 ,  A61K33/24 ,  Y10S514/824 ,  Y10S514/951

    摘要： A method of inhibiting the activity or production of cytokines or growth factors associated with vascular restenosis, by administering to an individual an effective amount of an active ingredient comprising a bisphosphonate particle or a bisphosphonate particulate. The bisphosphonate may be encapsulated, embedded or adsorbed within the particle, dispersed uniformly in the polymer matrix, adsorbed on the particle surface, or in combination of any of these forms. The particles include liposomes or inert polymeric particles, such as microcapsules, nanocapsules, nanoparticles, nanospheres, or microparticles. The particulates include any suspended or dispersed form of the bisphosphonate which is not encapsulated, entrapped, or adsorbed within a polymeric particle. The particulates include suspended or dispersed colloids, aggregates, flocculates, insoluble salts and insoluble complexes of the active ingredient. The cytokines and growth factors include, but are not limited to interleukin 1-β, matrix metalloproteinase-2, and platelet-derived growth factor β (PDGFβ).

    摘要翻译： 通过向个体施用有效量的包含双膦酸盐颗粒或二膦酸盐颗粒的活性成分来抑制与血管再狭窄相关的细胞因子或生长因子的活性或产生的方法。 双膦酸盐可以被包封，嵌入或吸附在颗粒内，均匀分散在聚合物基质中，吸附在颗粒表面上，或者结合任何这些形式。 颗粒包括脂质体或惰性聚合物颗粒，例如微胶囊，纳米胶囊，纳米颗粒，纳米球或微粒。 颗粒包括任何悬浮或分散形式的二膦酸盐，其不被包封，包埋或吸附在聚合物颗粒内。 颗粒包括悬浮或分散的胶体，聚集体，絮凝物，不溶性盐和活性成分的不溶性络合物。 细胞因子和生长因子包括但不限于白介素1-β，基质金属蛋白酶-2和血小板衍生生长因子β（PDGFbeta）。

    Compositions and Methods Using Same for Delivering Agents Into a Target Organ Protected by a Blood Barrier
    7.
    发明申请
    Compositions and Methods Using Same for Delivering Agents Into a Target Organ Protected by a Blood Barrier 有权
    使用同样的组合物和方法将药剂递送到由血液屏障保护的靶器官中

    公开(公告)号：US20100015213A1

    公开(公告)日：2010-01-21

    申请号：US11921022

    申请日：2006-05-25

    申请人： Gershon Golomb ,  Hila Epstein ,  Eyal Afergan

    发明人： Gershon Golomb ,  Hila Epstein ,  Eyal Afergan

    IPC分类号： A61K9/127 ,  A61P25/00

    CPC分类号： A61K9/127 ,  A61K9/0019

    摘要： A method of delivering a pharmaceutical agent into a target organ protected by a blood barrier is provided. The method comprising administering to a subject in need thereof an amount of liposomes which comprise the pharmaceutical agent, the amount and the liposomes are selected such that the liposomes accumulate in cells of an immune system of the subject to thereby generate liposome loaded immune cells, the liposome loaded immune cells become activated and cross the blood barrier, and an effective amount of the pharmaceutical agent is released from the liposomes in the target organ of the subject.

    摘要翻译： 提供了将药剂递送到由血液屏障保护的靶器官中的方法。 所述方法包括向有需要的受试者施用包含药剂的量的脂质体，所述量和脂质体选择为使得脂质体积聚在受试者的免疫系统的细胞中，由此产生负载脂质体的免疫细胞， 加载脂质体的免疫细胞变得活化并穿过血液屏障，并且有效量的药剂从受试者的靶器官中的脂质体释放。

    Carbamoyl-and thiocarbamoyl-phosphonates and pharmaceutical compositions comprising them
    8.
    发明授权
    Carbamoyl-and thiocarbamoyl-phosphonates and pharmaceutical compositions comprising them 失效
    氨基甲酰基 - 和硫代氨基甲酰基 - 膦酸酯和包含它们的药物组合物

    公开(公告)号：US07345033B2

    公开(公告)日：2008-03-18

    申请号：US11244405

    申请日：2005-10-06

    申请人： Eli Breuer ,  Reuven Reich ,  Gershon Golomb ,  Yiffat Katz

    发明人： Eli Breuer ,  Reuven Reich ,  Gershon Golomb ,  Yiffat Katz

    IPC分类号： A61K31/66 ,  C07F9/22

    CPC分类号： C07F9/4065 ,  C07F9/3891

    摘要： The present invention provides a compound of the following formula I: R3—NH—C(═X)—P(═O)OR1OR2 including pharmaceutically acceptable salts, solvates, hydrates and polymorphs of the compounds of formula I, as well as geometrical isomers and optically active forms of the compounds of formula I and pharmaceutically acceptable salts, solvates, hydrates and polymorphs of said isomers and forms, wherein R1 and R2 may be the same or different and are each selected from hydrogen, acyloxyalkyl and aryl or R1 and R2 may form together with the oxygen and phosphorus atoms a dioxaphosphacycloalkane ring; X is O or S; and R3 is selected, when X is O, from bicycloalkyl, cycloalkylalkyl and substituted cycloalkyl by at least one of alkyl, amino, amidino and guanidino; and R3 is selected, when X is S, from bicycloalkyl, cycloalkylalkyl and cycloalkyl optionally substituted by at least one of alkyl, amino, amidino and guanidino; with the proviso that: when X is O, R3 is not cyclohexylmethyl, and when X is S, R3 is not cyclohexyl. The invention further provides pharmaceutical compositions comprising the above compounds and their use in medicine.

    摘要翻译： 本发明提供下式I的化合物：<？在线式描述=“In-line formula”end =“lead”→R 3 -NH-C（-X ）-P（-O）OR 1或/或2“-in-line-formula description =”In-line Formulas“end =”tail“？>包括药学上可接受的 式I化合物的盐，溶剂合物，水合物和多晶型物，以及式I化合物的几何异构体和光学活性形式以及所述异构体和形式的药学上可接受的盐，溶剂合物，水合物和多晶型物，其中R 1和R 2可以相同或不同，并且各自选自氢，酰氧基烷基和芳基或R 1和R 2 >可与氧和磷原子一起形成二氧杂环磷杂环烷环; X是O或S; 当X为O时，R 3选自烷基，氨基，脒基和胍基中的至少一个来自双环烷基，环烷基烷基和取代环烷基; 当X为S时，选自二烷基，环烷基烷基和任选被烷基，氨基，脒基和胍基中的至少一个取代的环烷基; 条件是：当X是O时，R 3不是环己基甲基，当X是S时，R 3不是环己基。 本发明还提供了包含上述化合物及其在药物中的用途的药物组合物。

    Bis- and tetrakis-phosphonates useful for treating calcium related disorders
    10.
    发明授权
    Bis- and tetrakis-phosphonates useful for treating calcium related disorders 失效
    用于治疗钙相关疾病的双和四膦酸盐

    公开(公告)号：US5312954A

    公开(公告)日：1994-05-17

    申请号：US884291

    申请日：1992-05-13

    申请人： Eli Breuer ,  Gershon Golomb

    发明人： Eli Breuer ,  Gershon Golomb

    IPC分类号： C07F20060101 ,  C07F9/38 ,  C07F9/40 ,  C07F9/655

    CPC分类号： C07F9/3873 ,  C07F9/3886 ,  C07F9/405

    摘要： Novel bisphosphonates comprise compounds of the formula (I) ##STR1## wherein m and l are independently 1 or 2; R.sub.1 represents hydrogen, a lower alkyl group, or an alkali metal cation; R.sub.2 represents hydrogen, a lower alkyl group or an alkali metal cation; Y represents .dbd.0 or .dbd.N--OH, or --OH and X represents --(CH.sub.2).sub.n --, a branched alkylene group, or a branched or straight alkenylene or alkynylene chain optionally substituted by one or more oxygen or nitrogen atoms, wherein n is an integer from 3 to 24. Further definitions of X are included in the description.

    摘要翻译： 新型双膦酸盐包括式（I）化合物其中m和l独立地为1或2; R1表示氢，低级烷基或碱金属阳离子; R2代表氢，低级烷基或碱金属阳离子; Y表示= 0或= N-OH或-OH，X表示 - （CH 2）n - 支链亚烷基，或任选被一个或多个氧或氮原子取代的支链或直链亚烯基或亚炔基链，其中n 是3至24的整数。描述中包括X的其它定义。