公开(公告)号：US08128959B2

公开(公告)日：2012-03-06

申请号：US11918651

申请日：2006-04-13

申请人： Hiroshi Maeda ,  Khaled Greish

发明人： Hiroshi Maeda ,  Khaled Greish

IPC分类号： A61K47/48 ,  A61K33/30 ,  A61K31/555 ,  B01F3/00

CPC分类号： A61K41/0071 ,  A61K9/0019 ,  A61K9/107 ,  A61K31/409 ,  A61K31/704 ,  A61K31/7048 ,  A61K47/58 ,  A61K47/60 ,  C08K5/0091 ,  C08L35/06

摘要： The present invention provides a polymeric agent which can incorporate a large amount of a drug, accumulate selectively in a tumor site, and has a molecular size of more than that for renal excretion. A metalloporphyrin derivative (such as zinc protoporphyrin) is associated with a styrene-maleic acid copolymer via non-covalent bond to give a SMA micelle complex, allowing provision of a polymeric pharmaceutical agent for treatment of cancer with a large amount of the drug incorporated. The SMA micelle complex can be produced by a method, wherein the metalloporphyrin derivative reacts with the styrene-maleic acid copolymer in the absence of a condensation agent under an alkaline condition, solubilized, adjusted to have a pH of 6-8, and subjected to a procedure for separating a polymer component to recover the micelle complex component for the polymeric pharmaceutical agent.

摘要翻译： 本发明提供了可以掺入大量药物的聚合物，其选择性地积聚在肿瘤部位，并且具有比肾排泄量更大的分子大小。 金属卟啉衍生物（例如锌原卟啉锌）通过非共价键与苯乙烯 - 马来酸共聚物缔合，得到SMA胶束复合物，允许提供用于治疗癌症的大量药物的聚合物药剂。 SMA胶束复合物可以通过一种方法制备，其中金属卟啉衍生物在碱性条件下在不存在缩合剂的情况下与苯乙烯 - 马来酸共聚物反应，溶解，调节至pH为6-8，并进行 用于分离聚合物组分以回收聚合物药剂的胶束复合物组分的方法。

公开(公告)号：US20090062476A1

公开(公告)日：2009-03-05

申请号：US11918651

申请日：2006-04-13

申请人： Hiroshi Maeda ,  Khaled Greish

发明人： Hiroshi Maeda ,  Khaled Greish

IPC分类号： C08F8/30

CPC分类号： A61K41/0071 ,  A61K9/0019 ,  A61K9/107 ,  A61K31/409 ,  A61K31/704 ,  A61K31/7048 ,  A61K47/58 ,  A61K47/60 ,  C08K5/0091 ,  C08L35/06

摘要： The present invention provides a polymeric agent which can incorporate a large amount of a drug, accumulate selectively in a tumor site, and has a molecular size of more than that for renal excretion.A metalloporphyrin derivative (such as zinc protoporphyrin) is associated with a styrene-maleic acid copolymer via non-covalent bond to give a SMA micelle complex, allowing provision of a polymeric pharmaceutical agent for treatment of cancer with a large amount of the drug incorporated. The SMA micelle complex can be produced by a method, wherein the metalloporphyrin derivative reacts with the styrene-maleic acid copolymer in the absence of a condensation agent under an alkaline condition, solubilized, adjusted to have a pH of 6-8, and subjected to a procedure for separating a polymer component to recover the micelle complex component for the polymeric pharmaceutical agent.

摘要翻译： 本发明提供了可以掺入大量药物的聚合物，其选择性地积聚在肿瘤部位，并且具有比肾排泄量更大的分子大小。 金属卟啉衍生物（例如锌原卟啉锌）通过非共价键与苯乙烯 - 马来酸共聚物缔合，得到SMA胶束复合物，允许提供用于治疗癌症的大量药物的聚合物药剂。 SMA胶束复合物可以通过一种方法制备，其中金属卟啉衍生物在碱性条件下在不存在缩合剂的情况下与苯乙烯 - 马来酸共聚物反应，溶解，调节至pH为6-8，并进行 用于分离聚合物组分以回收聚合物药剂的胶束复合物组分的方法。

公开(公告)号：US07682630B2

公开(公告)日：2010-03-23

申请号：US10514892

申请日：2004-02-02

申请人： Hiroshi Maeda ,  Khaled Greish

发明人： Hiroshi Maeda ,  Khaled Greish

IPC分类号： A61K47/48 ,  A61K33/24 ,  A61K9/51

CPC分类号： A61K33/24 ,  A61K9/1075 ,  A61K47/58 ,  A61K47/6907

摘要： The present invention relates to polymeric antitumor agent which is formed in polymeric micelle complex by intermolecular bonding or mutual interaction between styrene maleic acid copolymer (SMA) and low molecule antitumor agent which is anthracyclins drug such as pirarubicin, doxorubicm, epirbicin, daunorbicin, acralbicin, or alkaloid antitumor agent such as cis-platinum, and taxol These polymeric antitumor agents may improve specificity to cancer cells so that it improves antitumor effect, while it may not be concentrated at normal organ or tissue, so that adverse effect may be diminished. These polymeric antitumor agents may be prepared by dissolving SMA and low molecule antitumor agent in aqueous solution, then in the presence of aqueous soluble carbodiimide, amino acids, or polyamine, adjusting pH to form micelle complex and recovering polymer fraction.

摘要翻译： 本发明涉及通过苯乙烯马来酸共聚物（SMA）和低分子抗肿瘤剂之间的分子间键合或相互作用形成聚合物胶束复合物的聚合物抗肿瘤剂，其是蒽环类药物，例如吡柔比星，多柔比星，表赤霉素，柔红霉素， 或生物碱抗肿瘤剂如顺铂和紫杉醇这些聚合抗肿瘤剂可以改善对癌细胞的特异性，从而提高抗肿瘤作用，而不会将其集中在正常的器官或组织，从而可能减少不良反应。 这些聚合抗肿瘤剂可以通过将SMA和低分子抗肿瘤剂溶解在水溶液中，然后在水溶性碳二亚胺，氨基酸或多胺的存在下，调节pH以形成胶束复合物并回收聚合物级分来制备。

公开(公告)号：US20050208136A1

公开(公告)日：2005-09-22

申请号：US10514892

申请日：2004-02-02

申请人： Hiroshi Maeda ,  Khaled Greish

发明人： Hiroshi Maeda ,  Khaled Greish

IPC分类号： A61K9/51 ,  A61K33/24 ,  A61K47/48 ,  A61P35/00 ,  A61K31/704 ,  A61K9/14

CPC分类号： A61K33/24 ,  A61K9/1075 ,  A61K47/58 ,  A61K47/6907

摘要： The present invention relates to polymeric antitumor agent which is formed in polymeric micelle complex by intermolecular bonding or mutual interaction between styrene maleic acid copolymer (SMA) and low molecule antitumor agent which is anthracyclins drug such as pirarubicin, doxorubicin, epirbicin, daunorbicin, acralbicin, or alkaloid antitumor agent such as cis-platinum, and taxol These polymeric antitumor agents may improve specificity to cancer cells so that it improves antitumor effect, while it may not be concentrated at normal organ or tissue, so that adverse effect may be diminished. These polymeric antitumor agents may be prepared by dissolving SMA and low molecule antitumor agent in aqueous solution, then in the presence of aqueous soluble carbodiimide, amino acids, or polyamine, adjusting pH to form micelle complex and recovering polymer fraction.

摘要翻译： 本发明涉及通过苯乙烯马来酸共聚物（SMA）和低分子抗肿瘤剂之间的分子间键合或相互作用在聚合物胶束复合物中形成的聚合物抗肿瘤剂，其是蒽环类药物，例如吡柔比星，多柔比星，表赤霉素，柔红霉素， 或生物碱抗肿瘤剂如顺铂和紫杉醇这些聚合抗肿瘤剂可以改善对癌细胞的特异性，从而提高抗肿瘤作用，而不会将其集中在正常的器官或组织，从而可能减少不良反应。 这些聚合抗肿瘤剂可以通过将SMA和低分子抗肿瘤剂溶解在水溶液中，然后在水溶性碳二亚胺，氨基酸或多胺的存在下，调节pH以形成胶束复合物并回收聚合物级分来制备。