公开(公告)号：US06310039B1

公开(公告)日：2001-10-30

申请号：US09254598

申请日：1999-05-21

申请人： Felix Kratz

发明人： Felix Kratz

IPC分类号： A61K3838

CPC分类号： C07K14/79 ,  A61K38/00 ,  A61K47/62 ,  A61K47/643 ,  A61K47/644 ,  A61K47/65 ,  C07K14/76

摘要： Conjugates of transferrin, albumin and polyethylence glycol consisting of native or thiolated transferrin or albumin or of polyethylene glycol (MW between approximately 5,000 and 20,0000) with at least one HS—, HO— or H2N group and cytostatic compounds derived through maleinimide or N-hydroxysuccinimide ester compounds, such as doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxandrone, chloroambucil, melphalan, 5-fluorouracyl, 5′-desoxy-5-fluorouridine, thioguanine, methotrexate, paclitaxel, docetaxel, topotecan, 9-aminocamptothecin, etoposide, teniposide, mitopodoside, vinblastine, vincristine, vindesine, vinorelbine or a compound of general formula A, B, C or D, where n=0-6, X=—NH2, —OH, —COOH, —O—CO—R—COR*, —NH—CO—R—COR*, where R is an aliphatic carbon chain with 1-6 carbon atoms or a substituted or unsubstituted phenylene group and R* H, phenyl, alkyl with 1-6 carbon atoms.

摘要翻译： 由天然或硫醇化转铁蛋白或白蛋白或聚乙二醇（约5,000至20,0000的MW）与至少一种HS-，HO-或H2N基团组成的转铁蛋白，白蛋白和聚乙二醇的结合物和通过马来酰亚胺或N 羟基琥珀酰亚胺酯化合物，如多柔比星，柔红霉素，表柔比星，伊达比星，米托蒽醌，氯氮芥，美法仑，5-氟尿嘧啶，5'-脱氧-5-氟尿苷，硫鸟嘌呤，甲氨蝶呤，紫杉醇，多西他赛，托泊替康，9-氨基喜树碱，依托泊苷， 替尼泊苷，mitopodoside，长春花碱，长春新碱，长春地辛，长春瑞滨或通式A，B，C或D的化合物，其中n = 0-6，X = -NH2，-OH，-COOH，-O-CO-R- COR *，-NH-CO-R-COR *，其中R是具有1-6个碳原子的脂族碳链或取代或未取代的亚苯基，R * H，苯基，具有1-6个碳原子的烷基。

公开(公告)号：US06191105B1

公开(公告)日：2001-02-20

申请号：US08958383

申请日：1997-10-27

申请人： Nnochiri Nkem Ekwuribe ,  Muthukumar Ramaswamy ,  Balasingam Radhakrishnan ,  HameedSulthan S. Allaudeen

发明人： Nnochiri Nkem Ekwuribe ,  Muthukumar Ramaswamy ,  Balasingam Radhakrishnan ,  HameedSulthan S. Allaudeen

IPC分类号： A61K3838

CPC分类号： C12N9/96 ,  A61K9/1075 ,  A61K9/4858 ,  A61K38/00 ,  A61K47/56 ,  A61K47/60 ,  C07K1/1077 ,  C07K14/62

摘要： A therapeutic formulation comprising a microemulsion of a therapeutic agent in free and/or conjugatively coupled form, wherein the microemulsion comprises a water-in-oil (w/o) microemulsion including a lipophilic phase and a hydrophilic phase, and has a hydrophilic and lipophilic balance (HLB) value between 3 and 7, wherein the therapeutic agent may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, papain, Ara-A (Arabinofuranosyladenine), Acylguanosine, Nordeoxyguanosine, Azidothymidine, Dideoxyadenosine, Dideoxycytidine, Dideoxyinosine Floxuridine, 6-Mercaptopurine, Doxorubicin, Daunorubicin, or I-darubicin, Erythromycin, Vancomycin, oleandomycin, Ampicillin; Quinidine and Heparin. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. The microemulsion compositions of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications.

公开(公告)号：US06709679B2

公开(公告)日：2004-03-23

申请号：US09931940

申请日：2001-08-20

申请人： Felix Kratz

发明人： Felix Kratz

IPC分类号： A61K3838

CPC分类号： C07K14/79 ,  A61K38/00 ,  A61K47/62 ,  A61K47/643 ,  A61K47/644 ,  A61K47/65 ,  C07K14/76

摘要： Conjugates of transferrin, albumin and polyethylence glycol consisting of native or thiolated transferrin or albumin or of polyethylene glycol (MW between approximately 5,000 and 20,0000) with at least one HS—, HO— or H2N group and cytostatic compounds derived through maleinimide or N-hydroxysuccinimide ester compounds, such as doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxandrone, chloroambucil, melphalan, 5-fluorouracyl, 5′-desoxy-5-fluorouridine, thioguanine, methotrexate, paclitaxel, docetaxel, topotecan, 9-aminocamptothecin, etoposide, teniposide, mitopodoside, vinblastine, vincristine, vindesine, vinorelbine or a compound of general formula A, B, C or D, where n=0-6, X=—NH2, —OH, —COOH, —O—CO—R—COR*, —NH—CO—R—COR*, where R is an aliphatic carbon chain with 1-6 carbon atoms or a substituted or unsubstituted phenylene group and R*H, phenyl, alkyl with 1-6 carbon atoms.

摘要翻译： 由天然或硫醇化转铁蛋白或白蛋白或聚乙二醇（约5,000至20,0000的MW）与至少一种HS-，HO-或H2N基团组成的转铁蛋白，白蛋白和聚乙二醇的结合物和通过马来酰亚胺或N 羟基琥珀酰亚胺酯化合物，如多柔比星，柔红霉素，表柔比星，伊达比星，米托蒽醌，氯氮芥，美法仑，5-氟尿嘧啶，5'-脱氧-5-氟尿苷，硫鸟嘌呤，甲氨蝶呤，紫杉醇，多西他赛，托泊替康，9-氨基喜树碱，依托泊苷， 替尼泊苷，mitopodoside，长春花碱，长春新碱，长春地辛，长春瑞滨或通式A，B，C或D的化合物，其中n = 0-6，X = -NH2，-OH，-COOH，-O-CO-R- COR *，-NH-CO-R-COR *，其中R是具有1-6个碳原子的脂族碳链或取代或未取代的亚苯基，R * H，苯基，具有1-6个碳原子的烷基。

公开(公告)号：US06458758B1

公开(公告)日：2002-10-01

申请号：US08824739

申请日：1997-03-26

申请人： Jen-Chang Hsia

发明人： Jen-Chang Hsia

IPC分类号： A61K3838

CPC分类号： B82Y5/00 ,  A61K38/42 ,  A61K45/06 ,  A61K47/52 ,  A61K47/6445 ,  A61K47/6895 ,  A61K49/0002 ,  A61K49/20 ,  C07K14/76 ,  C07K14/805 ,  C07K16/00 ,  A61K2300/00

摘要： Compositions and processes to alleviate free radical toxicity are disclosed based on the use of nitroxides in association with physiologically compatible macromolecules. In particular, hemoglobin-based red cell substitutes are described featuring stable nitroxide free radicals for use in cell-free hemoglobin solutions, encapsulated hemoglobin solutions, stabilized hemoglobin solutions, polymerized hemoglobin solutions, conjugated hemoglobin solutions, nitroxide-labelled albumin, and nitroxide-labelled immunoglobulin. Formulations are described herein that interact with free radicals, acting as antioxidant enzyme-mimics, which preserve nitroxides in their active form in vivo. Applications are described including blood substitutes, radioprotective agents, imaging agents, agents to protect against ischemia and reperfusion injury, particularly in cerebral ischemia in stroke, and in vivo enzyme mimics among others.

摘要翻译： 基于与生理上相容的大分子结合使用的氮氧化物，公开了减轻自由基毒性的组合物和方法。 特别地，描述了基于血红蛋白的红细胞替代物，其特征在于稳定的氮氧自由基用于无细胞血红蛋白溶液，包封的血红蛋白溶液，稳定的血红蛋白溶液，聚合血红蛋白溶液，共轭血红蛋白溶液，氮氧自由基标记的白蛋白和氮氧化物标记 免疫球蛋白。 本文描述了与自由基相互作用的制剂，其作为抗氧化酶模拟物，其在体内保护其活性形式的氮氧化物。 描述了应用，包括血液代用品，放射防护剂，成像剂，防止缺血和再灌注损伤的药剂，特别是中风中的脑缺血以及体内酶模拟物等。