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公开(公告)号：US5286714A
公开(公告)日：1994-02-15
申请号：US985110
申请日：1992-12-03
IPC分类号： A61K38/55 , A61K38/00 , A61P7/02 , C07K1/14 , C07K14/00 , C07K14/815 , C12N15/09 , C12N15/12 , C12P21/02 , C12R1/19 , C07K7/10 , A61K37/64
CPC分类号： C07K14/815 , A61K38/00
摘要： The invention relates to novel synthetic isohirudins which have improved stability owing to exchange in the region of the Asp-Gly motif. This results, on the one hand, in an increase in the yield during workup and, on the other hand, in making possible pharmaceutical formulation as directly injectable solution ready for use.
摘要翻译： 本发明涉及由Asp-Gly基序区域中的交换而具有改善的稳定性的合成异水蛭素。 一方面，这导致加工时产量增加，另一方面，在作为直接注射溶液的药物制剂中是可能的。
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公开(公告)号：US5616476A
公开(公告)日：1997-04-01
申请号：US452829
申请日：1995-05-30
IPC分类号： A61K38/55 , A61K38/00 , A61P7/02 , C07K1/14 , C07K14/00 , C07K14/815 , C12N15/09 , C12N15/12 , C12P21/02 , C12R1/19 , C12P21/06 , C07H19/00 , C12N5/00
CPC分类号： C07K14/815 , A61K38/00
摘要： The invention relates to novel synthetic isohirudins which have improved stability owing to exchange in the region of the Asp-Gly motif. This results, on the one hand, in an increase in the yield during workup and, on the other hand, in making possible pharmaceutical formulation as directly injectable solution ready for use.
摘要翻译： 本发明涉及由于Asp-Gly基序区域交换而具有改善的稳定性的新型合成异水蛭素。 这一方面导致了在后处理期间产量的增加，另一方面，使可能的药物制剂成为可直接注射的溶液使用。
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公开(公告)号：US5316947A
公开(公告)日：1994-05-31
申请号：US99053
申请日：1993-07-29
IPC分类号： A61K38/55 , A61K38/00 , A61P7/02 , C07K1/14 , C07K14/00 , C07K14/815 , C12N15/09 , C12N15/12 , C12P21/02 , C12R1/19 , C12N15/20 , C12N15/63 , C12N15/81
CPC分类号： C07K14/815 , A61K38/00
摘要： Novel synthetic isohirudins with improved stability The invention relates to novel synthetic isohirudins which have improved stability owing to exchange in the region of the Asp-Gly motif. This results, on the one hand, in an increase in the yield during workup and, on the other hand, in making possible pharmaceutical formulation as directly injectable solution ready for use.
摘要翻译： 具有改进的稳定性的新型合成异水蓝蛋白本发明涉及由于Asp-Gly基序区域中的交换而具有改善的稳定性的新型合成异水蛭素。 这一方面导致了在后处理期间产量的增加，另一方面，使可能的药物制剂成为可直接注射的溶液使用。
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公开(公告)号：US5322926A
公开(公告)日：1994-06-21
申请号：US35498
申请日：1993-03-22
申请人： Dominique Tripier , Peter Crause , Paul Habermann , Martin Kramer , Joachim Engels , Matthias Scharf
发明人： Dominique Tripier , Peter Crause , Paul Habermann , Martin Kramer , Joachim Engels , Matthias Scharf
IPC分类号： A61K38/55 , A61K38/00 , A61P7/02 , C07K1/02 , C07K1/113 , C07K1/14 , C07K1/20 , C07K1/22 , C07K14/81 , C07K14/815 , A61K37/00 , A61K37/02 , C07K5/00 , C07K7/00
CPC分类号： C07K14/815 , A61K38/00
摘要： Thrombin inhibitors from the hirudin family which differ from the previously known hirudins by mutation in the protein chain, and a process for their preparation are described. The novel hirudins are distinguished by a high specific activity, high stability and good pharmacokinetics.
摘要翻译： 描述了水蛭素家族中不同于先前已知的水蛭素蛋白质链中突变的凝血酶抑制剂及其制备方法。 水蛭素具有高比活性，高稳定性和良好的药动学特征。
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公开(公告)号：US5180668A
公开(公告)日：1993-01-19
申请号：US295422
申请日：1989-01-10
申请人： Peter Crause , Paul Habermann , Dominique Tripier
发明人： Peter Crause , Paul Habermann , Dominique Tripier
IPC分类号： C12P21/02 , A61K38/00 , A61K38/55 , A61P7/02 , C07H21/04 , C07K1/20 , C07K14/00 , C07K14/815 , C12N15/09 , C12R1/865
CPC分类号： C07K14/815 , A61K38/00 , Y10S530/855
摘要： A hirudin derivative which has the N-terminal amino acid sequence Leu-Thr-Tyr-Thr-Asp shows high biological activity. Moreover, this hirudin derivative can be obtained very efficiently by genetic engineering preparation in yeasts.
摘要翻译： 具有N-末端氨基酸序列Leu-Thr-Tyr-Thr-Asp的水蛭素衍生物显示出高生物活性。 此外，通过在酵母中的遗传工程制备，可以非常有效地获得该水蛭素衍生物。
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公开(公告)号：US5095092A
公开(公告)日：1992-03-10
申请号：US590581
申请日：1990-09-27
IPC分类号： G01N30/88 , B01D15/08 , C07K1/20 , C07K14/00 , C07K14/435 , C07K14/815 , G01N30/26
CPC分类号： C07K14/815
摘要： The invention relates to a process for the isolation and purification of hirudin from complex and salt-containing solutions by hydrophobic chromatography, using as stationary phase porous adsorber resins and as mobile phase organic solvents which are miscible with water.
摘要翻译： 本发明涉及一种通过疏水色谱法分离和纯化水蛭素从复合盐和含盐溶液中分离和纯化的方法，使用作为固定相多孔吸附树脂和作为与水混溶的流动相有机溶剂。
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公开(公告)号：US5538946A
公开(公告)日：1996-07-23
申请号：US895436
申请日：1992-06-05
申请人： Peter Crause , Paul Habermann , Martin Kramer , Rainer Obermeier , Klaus Sauber , Dominique Tripier
发明人： Peter Crause , Paul Habermann , Martin Kramer , Rainer Obermeier , Klaus Sauber , Dominique Tripier
IPC分类号： C12N9/99 , A61K38/00 , A61K38/55 , A61K47/48 , A61P7/02 , C07K1/113 , C07K1/20 , C07K1/22 , C07K14/81 , C07K14/815 , C07K17/10 , C12P21/02 , C12R1/645 , C07K5/00 , C07K7/00 , C07K3/00
CPC分类号： A61K47/4823 , C07K14/815 , A61K38/00
摘要： The present invention relates to hirudin derivatives which are formed from hirudin or the physiologically acceptable salt thereof and a carrier, to a process for the preparation thereof, and to the use thereof as thrombin inhibitor.
摘要翻译： 本发明涉及由水蛭素或其生理学上可接受的盐和载体形成的水蛭素衍生物，其制备方法及其作为凝血酶抑制剂的用途。
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8.发明授权Process for inactivating carboxypeptidase Y in hirudin-containing culture broths 失效在含水蛭素的培养液中灭活羧肽酶Y的方法
公开(公告)号：US5866399A
公开(公告)日：1999-02-02
申请号：US695434
申请日：1996-08-12
申请人： Peter Crause , Paul Habermann , Jorg Moller , Wolfgang Ulmer
发明人： Peter Crause , Paul Habermann , Jorg Moller , Wolfgang Ulmer
IPC分类号： C12N9/48 , C07K14/815 , C12N1/19 , C12N9/99 , C12P21/00 , C12P21/02 , C12R1/865 , C12N9/50 , A23J1/00 , C12M1/32 , C12N1/14
CPC分类号： C12P21/02 , C07K14/815
摘要： The present invention relates to a process for inactivating Carboxypeptidase Y (CPY) in a hirudin-containing culture broth produced by fermenting a transformed yeast. It has been found that inactive precursors of CPY are activated at a temperature 70.degree. C. and that the active peptidases will further degrade hirudin when the two proteins are present together in a composition. The present invention overcomes the CPY activation problem by heating a broth containing hirudin and CPY to a temperature of about 80.degree.-100.degree. C. in about one minute or less.
摘要翻译： 本发明涉及通过发酵转化的酵母产生的含水蛭素的培养液中灭活羧肽酶Y（CPY）的方法。 已经发现，CPY的无活性前体在70℃的温度下被活化，并且当两种蛋白质在组合物中一起存在时，活性肽酶将进一步降解水蛭素。 本发明通过在约1分钟或更短的时间内将含有水蛭素和CPY的肉汤加热至约80℃-100℃的温度来克服CPY活化问题。
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9.发明授权Tick-derived amblyommin and method of antithrombin therapy 失效TICK-DERIVED AMBLYOMMIN AND METHOD OF ANTIROMBIN THERAPY
公开(公告)号：US5093322A
公开(公告)日：1992-03-03
申请号：US360573
申请日：1989-06-02
IPC分类号： A61K38/55 , A61K35/56 , A61K38/00 , A61P7/02 , C07K1/14 , C07K1/16 , C07K14/00 , C07K14/435 , C07K14/44 , C07K14/81
CPC分类号： C07K14/43527 , A61K35/646 , C07K14/811 , A61K38/00 , Y10S530/855
摘要： The invention relates to a new active substance--amblyommin--for anticoagulant therapy and to a process for the isolation thereof from hard ticks. The isolated protein having a thrombin-inhibitory action has a molecular weight of 20000 to 30000 dalton, an isoelectric point between 5.05 and 5.65 and the partial amino acid sequencesIle-Leu-Phe-Thr-Gln-Gly-Asn-X-Gly-Glu-Leu-Glu-Asn-X-Phe-Glu-,Lys-Ile-Leu-Phe-X-Gln-Gly- andAla-Ser-Tyr-Ile-Val-X-Ser-Glu-Ser-Ile-Gln-Ile-Leu-X-Leu-Ser-Glu-Gly-Ile-in which each radical X can be identical or different and each represents a naturally occurring amino acid.
摘要翻译： 本发明涉及用于抗凝治疗的新型活性物质 - 抗凝血酶活性物质，以及将其与硬蜱分离的方法。 具有凝血酶抑制作用的分离蛋白质的分子量为20000〜30000道尔顿，等电点为5.05〜5.65，部分氨基酸序列Ile-Leu-Phe-Thr-Gln-Gly-Asn-X-Gly- Glu-Leu-Glu-Asn-X-Phe-Glu-，Lys-Ile-Leu-Phe-X-Gln-Gly-和Ala-Ser-Tyr-Ile-Val-X-Ser-Glu-Ser- Gln-Ile-Leu-X-Leu-Ser-Glu-Gly-Ile-，其中每个基团X可以相同或不同，并且各自表示天然存在的氨基酸。
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公开(公告)号：US5227293A
公开(公告)日：1993-07-13
申请号：US838221
申请日：1992-04-23
CPC分类号： C07K14/62 , C12N15/62 , C07K2319/00 , C07K2319/02 , C07K2319/35 , C07K2319/75
摘要： Fusion proteins are obtained in high yields if a mixed oligonucleotide is constructed which codes for the ballast constituent of the fusion protein. The oligonucleotide mixture is introduced in a vector in such a manner that it is functionally linked to a regulatory region and to the structural gene for the desired protein. Appropriate host cells are transformed with the plasmid population obtained in this manner and the clones producing a high yield of coded fusion protein are selected.
摘要翻译： 如果构建编码融合蛋白的镇流成分的混合寡核苷酸，则以高产率获得融合蛋白。 将寡核苷酸混合物以这样的方式引入载体中，使得其功能上连接到调节区域和所需蛋白质的结构基因。 用以这种方式获得的质粒群转化合适的宿主细胞，并选择产生高产量的编码融合蛋白的克隆。
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