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11 条记录 (耗时 0.047 秒)

    Succinylated interleukin-2 for pharmaceutical compositions
    4.
    发明授权
    Succinylated interleukin-2 for pharmaceutical compositions 失效
    用于药物组合物的琥珀酰白介素-2

    公开(公告)号：US4931544A

    公开(公告)日：1990-06-05

    申请号：US148106

    申请日：1988-01-27

    申请人： Nandini Katre ,  Michael J. Knauf

    发明人： Nandini Katre ,  Michael J. Knauf

    IPC分类号： A61K9/52 ,  A61K38/00 ,  C07K14/55

    CPC分类号： C07K14/55 ,  A61K38/00

    摘要： A pharmaceutical composition is prepared wherein biologically active conjugated interleukin-2 is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated IL-2, which is not water soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to one or more succinyl groups by reaction with succinic anhydride.

    摘要翻译： 制备药物组合物，其中将生物活性共轭白细胞介素-2溶解在含水载体介质中而不存在增溶剂。 不结合的IL-2不溶于水或不易溶于pH6-8的水，而不含这种增溶剂，通过与琥珀酸酐反应选择性地与一个或多个琥珀酰基基团结合。

    Preparation of a polymer/interleukin-2 conjugate
    5.
    发明授权
    Preparation of a polymer/interleukin-2 conjugate 失效
    聚合物/白介素-2缀合物的制备

    公开(公告)号：US4902502A

    公开(公告)日：1990-02-20

    申请号：US299235

    申请日：1989-01-23

    申请人： Danute E. Nitecki ,  Nandini Katre ,  Robert J. Goodson ,  Lois Aldwin

    发明人： Danute E. Nitecki ,  Nandini Katre ,  Robert J. Goodson ,  Lois Aldwin

    IPC分类号： A61K47/48

    CPC分类号： A61K47/48215

    摘要： The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase it solubility, and increase its circulating in vivo half-life.

    摘要翻译： 本发明是一种制备包含生物活性共轭蛋白质的药物组合物的方法。 它包含与IL-2缀合的聚乙二醇或聚氧乙烯化多元醇。 这种蛋白质被缀合以降低其免疫原性，并增加其溶解度，并增加其体内循环体内的半衰期。

    High and low load formulations of IGF-I in multivesicular liposomes
    6.
    发明授权
    High and low load formulations of IGF-I in multivesicular liposomes 失效
    IGF-I在多泡脂质体中的高负荷和低负荷配方

    公开(公告)号：US06306432B1

    公开(公告)日：2001-10-23

    申请号：US08925531

    申请日：1997-09-08

    申请人： Bret Shirley ,  Maninder Hora ,  Qiang Ye ,  Nandini Katre ,  John Asherman

    发明人： Bret Shirley ,  Maninder Hora ,  Qiang Ye ,  Nandini Katre ,  John Asherman

    IPC分类号： A61K9127

    CPC分类号： A61K9/1277 ,  A61K38/30

    摘要： Disclosed are multivesicular liposomes (MVLs) containing IGF-I with substantially full bioavailability, wherein the loading of the IGF-I into the liposomes is modulated by adjusting the osmolarity of the aqueous component into which the agents are dissolved prior to encapsulation. In the making of MVLs, the process involves dissolving the IGF-I, an osmolarity excipient, and a pH modifying agent sufficient to solubilize the IGF-I in a first aqueous component used during manufacture of the MVLs. To increase the loading of the IGF-I, the osmolarity of the aqueous component used during manufacture of the MVLs is reduced, whereas the osmolarity of the aqueous component is increased to obtain the low load formulations. The rate of release of the active agent into the surrounding environment in which the liposomes are introduced can be simultaneously controlled by incorporating into the lipid component used in the formulation at least one long chain amphipathic lipid. Use of the long chain amphipathic lipid in the lipid component is particularly helpful in controlling the release rate from high drug load formulations.

    摘要翻译： 公开了含有基本上具有完全生物利用度的IGF-I的多泡脂质体（MVL），其中通过在包封之前调节其中溶解有药剂的水性组分的渗透压，调节IGF-1进入脂质体的载体。 在制备MVL时，该方法包括将制备所述MVL的第一水性成分中的IGF-I，渗透性赋形剂和pH调节剂溶解在足以溶解IGF-I的第一水溶性成分中。 为了增加IGF-I的负载量，在制造MVL期间使用的水性组分的渗透压降低，而水性组分的渗透压增加以获得低负荷制剂。 引入脂质体的周围环境中活性剂的释放速率可以通过将至少一种长链两亲性脂质掺入用于制剂中的脂质组分中来同时控制。 在脂质组分中使用长链两亲脂质特别有助于控制高药物负荷制剂的释放速率。

    Modulation of drug loading in multivescular liposomes
    7.
    发明授权
    Modulation of drug loading in multivescular liposomes 失效
    多重脂质体中药物负载的调节

    公开(公告)号：US6106858A

    公开(公告)日：2000-08-22

    申请号：US925532

    申请日：1997-09-08

    申请人： Qiang Ye ,  Nandini Katre ,  Mantripragada Sankaram

    发明人： Qiang Ye ,  Nandini Katre ,  Mantripragada Sankaram

    IPC分类号： A61K9/127 ,  A61K31/485 ,  A61K31/7068 ,  A61K38/04 ,  A61K38/22 ,  A61K38/24 ,  A61K45/00 ,  A61K47/04 ,  A61K47/06 ,  A61K47/10 ,  A61K47/12 ,  A61K47/14 ,  A61K47/16 ,  A61K47/18 ,  A61K47/26 ,  A61K47/36 ,  A61P3/10 ,  A61P5/00 ,  A61P9/00 ,  A61P9/04 ,  A61P9/06 ,  A61P9/12 ,  A61P11/06 ,  A61P23/00 ,  A61P25/04 ,  A61P25/20 ,  A61P25/22 ,  A61P29/00 ,  A61P31/10 ,  A61P31/12 ,  A61P35/00 ,  A61P37/02

    CPC分类号： A61K9/127

    摘要： Disclosed is a method for making liposomes, for example multivesicular liposomes (MVLs), containing one or more biologically active agents, wherein the loading of the active agents into the liposomes is modulated by adjusting the osmolarity of the aqueous component into which the agents are dissolved prior to encapsulation. To increase the loading of the active agent, the osmolarity of the aqueous component is reduced, and to decrease the loading of the active agent, the osmolarity of the aqueous component is increased. In the making of MVLs, the process involves dissolving the active agent and an optional osmotic excipient in a first aqueous component encapsulated within the liposomes. For any given concentration of drug, the osmolarity of the first aqueous component can be adjusted by increasing or decreasing the concentration or molecular weight of the osmotic excipients used therein. The rate of release of the active agent into the surrounding environment in which the liposomes are introduced can be simultaneously controlled by incorporating into the lipid component used in the formulation at least one long chain amphipathic lipid. For example, the amphipathic lipid can have from about 13 to about 28 carbons in its carbon chain. Use of the long chain amphipathic lipid in the lipid component is particularly helpful in controlling the release rate and encapsulation efficiency for high drug load formulations.

    摘要翻译： 公开了一种制备脂质体的方法，例如含有一种或多种生物活性剂的多泡脂质体（MVL），其中通过调节试剂溶解于其中的水性组分的渗透压来调节活性剂向脂质体中的负载 在封装之前。 为了增加活性剂的负载量，水性组分的渗透压降低，并且为了降低活性剂的负载量，水性组分的渗透压增加。 在制备MVL时，该方法包括将活性剂和任选的渗透性赋形剂溶解在包封在脂质体内的第一含水组分中。 对于任何给定的药物浓度，可以通过增加或降低其中使用的渗透性赋形剂的浓度或分子量来调节第一含水组分的渗透压。 引入脂质体的周围环境中活性剂的释放速率可以通过将至少一种长链两亲性脂质掺入用于制剂中的脂质组分中来同时控制。 例如，两亲性脂质在其碳链中可以具有约13至约28个碳。 在脂质组分中使用长链两亲脂质特别有助于控制高药物负荷制剂的释放速率和包封效率。

    Interleukin-2 muteins and polymer conjugation thereof
    8.
    发明授权
    Interleukin-2 muteins and polymer conjugation thereof 失效
    白细胞介素-2突变蛋白及其聚合物缀合物

    公开(公告)号：US5206344A

    公开(公告)日：1993-04-27

    申请号：US142467

    申请日：1988-01-11

    申请人： Nandini Katre ,  Robert F. Halenbeck ,  Robert J. Goodson ,  Peter C. McCabe ,  Michael J. Knauf

    发明人： Nandini Katre ,  Robert F. Halenbeck ,  Robert J. Goodson ,  Peter C. McCabe ,  Michael J. Knauf

    IPC分类号： A61K38/20 ,  A61K38/21 ,  A61K47/48 ,  C07K1/107

    CPC分类号： A61K47/48215 ,  A61K38/2013 ,  A61K38/215 ,  A61K47/48476 ,  C07K1/1077 ,  Y10S930/141

    摘要： Muteins of IL-2 in which one of the amino acids of the mature native sequence of IL-2 is replaced by a cysteine residue are prepared and conjugated through the replaced cysteine residue to a polymer selected from polyethylene glycol homopolymers or polyoxyethylated polyols, wherein said homopolymers are unsubstituted or substituted at one end with an alkyl group. These muteins are made via host expression of mutant genes encoding the muteins that have been changed from the genes for the parent proteins by site-directed mutagenesis. In addition, other species of IL-2 may be conjugated via the cysteine residue at position 125 of the mature IL-2 protein that is not necessary for the biological activity of the IL-2.

    摘要翻译： 制备其中IL-2的成熟天然序列的一个氨基酸被半胱氨酸残基取代的IL-2的突变蛋白，并通过所述替换的半胱氨酸残基与选自聚乙二醇均聚物或聚氧乙烯化多元醇的聚合物缀合，其中所述 均聚物是未取代的或在一端被烷基取代。 这些突变蛋白是通过宿主表达编码突变蛋白的突变基因，通过定点突变从母体蛋白的基因中改变的突变蛋白。 此外，IL-2的其它物质可以通过成熟IL-2蛋白的125位的半胱氨酸残基而被结合，这对于IL-2的生物活性是不必要的。

    Preparation of a polymer/interleukin-2 conjugate
    9.
    发明授权
    Preparation of a polymer/interleukin-2 conjugate 失效
    聚合物/白介素-2缀合物的制备

    公开(公告)号：US5089261A

    公开(公告)日：1992-02-18

    申请号：US415046

    申请日：1989-09-29

    申请人： Danute E. Nitecki ,  Nandini Katre ,  Robert J. Goodson ,  Lois Aldwin

    发明人： Danute E. Nitecki ,  Nandini Katre ,  Robert J. Goodson ,  Lois Aldwin

    IPC分类号： A61K47/48

    CPC分类号： A61K47/48215

    摘要： The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase its solubility, and increase its circulating in vivo half-life.

    摘要翻译： 本发明是一种制备包含生物活性共轭蛋白质的药物组合物的方法。 它包含与IL-2缀合的聚乙二醇或聚氧乙烯化多元醇。 该蛋白质被缀合以降低其免疫原性，并增加其溶解度，并增加其体内循环体内的半衰期。

    Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation
    10.
    发明授权
    Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation 失效
    使用聚合物缀合对药物组合物的免疫毒素进行溶解

    公开(公告)号：US4917888A

    公开(公告)日：1990-04-17

    申请号：US131901

    申请日：1987-12-11

    申请人： Nandini Katre ,  Michael J. Knauf

    发明人： Nandini Katre ,  Michael J. Knauf

    IPC分类号： A61K38/20 ,  A61K38/21 ,  A61K47/48 ,  C07K1/107

    CPC分类号： A61K47/48215 ,  A61K38/2013 ,  A61K38/215 ,  A61K47/48476 ,  C07K1/1077

    摘要： A pharmaceutical composition is prepared wherein a biologically active conjugated protein which is .beta.-interferon, interleukin-2, or an immunotoxin is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated protein, which is not water-soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to a water-soluble polymer selected from polyethylene glycol homopolymers or polyoxyethylated polyols.

    摘要翻译： 制备药物组合物，其中将β-干扰素，白细胞介素-2或免疫毒素的生物活性缀合蛋白溶解在含水载体介质中而不存在增溶剂。 选择性地与选自聚乙二醇均聚物或聚氧乙烯化多元醇的水溶性聚合物共轭未结合的蛋白质，其不溶于水或不易溶于pH6-8的水中而无这种增溶剂。