公开(公告)号：US5068106A

公开(公告)日：1991-11-26

申请号：US201880

申请日：1988-06-03

申请人： Eric P. Paques ,  Hans-Arnold Stohr

发明人： Eric P. Paques ,  Hans-Arnold Stohr

IPC分类号： C12N9/64 ,  A61K38/46 ,  A61K38/49 ,  A61K47/18 ,  A61L2/00 ,  A61P7/02 ,  C12N9/96

CPC分类号： C12N9/96 ,  A61K38/49 ,  A61K47/183 ,  A61K9/0019 ,  A61L2/0023

摘要： In the preparation of parenteral solutions for the therapy and prophylaxis of thromboses and embolisms, because of the poor solubility of t-PA hitherto either the infusion of very large volumes has been necessary, or else a solution with a low volume and a high t-PA concentration has been prepared at the expense of setting up a non-physiologically low pH of 2 to 5.Hence, the present invention relates to a process for the preparation of a solution of high concentration of a protein having plasminogen activator activity, where an increase in stability and solubility is achieved by adding at least two substances from the group of D- and/or L-amino acids, their salts, derivatives or homologs. This invention also relates to a process for the pasteurization of a protein solution having t-PA activity, and to a t-PA-containing solution prepared by the claimed process, and to the use of this solution as a fibrinolytic in human and veterinary medicine.

摘要翻译： 在制备用于治疗和预防血栓栓塞和肠栓塞的肠胃外溶液中，由于t-PA的溶解性差，所以必须输入非常大的体积，或者是具有低体积和高t- 已经以建立2至5的非生理学低pH为代价制备了PA浓度。因此，本发明涉及一种制备高浓度具有纤溶酶原激活剂活性的蛋白质的溶液的方法，其中 通过从D-和/或L-氨基酸，其盐，衍生物或同系物组中加入至少两种物质来实现稳定性和溶解度的增加。 本发明还涉及一种用于将具有t-PA活性的蛋白质溶液巴氏杀菌的方法以及通过所要求保护的方法制备的含有t-PA的溶液的方法，以及该溶液在人和兽医学中作为纤维蛋白溶解剂的用途 。

公开(公告)号：US5501853A

公开(公告)日：1996-03-26

申请号：US944117

申请日：1986-12-22

申请人： Nancy L. Haigwood ,  Ernest-Guenter Afting ,  Guy Mullenbach ,  Eric P. Paques

发明人： Nancy L. Haigwood ,  Ernest-Guenter Afting ,  Guy Mullenbach ,  Eric P. Paques

IPC分类号： C12N9/64 ,  A61K38/00 ,  A61K38/46 ,  A61K38/48 ,  A61P7/02 ,  C07H21/04 ,  C07K14/745 ,  C12N5/00 ,  C12N5/10 ,  C12N9/72 ,  C12N15/00 ,  C12N15/09 ,  C12N15/10 ,  C12N15/55 ,  C12N15/58 ,  C12P21/00 ,  C12R1/91 ,  A61K38/49

CPC分类号： C12N9/6459 ,  C12N15/10 ,  C12Y304/21069

摘要： Novel polypeptide compositions based on the amino acid sequence of tissue plasminogen activator (tPA) are provided having improved properties over natural tissue plasminogen activator. Particularly, enhanced specific activity, reduced response to inhibition by plasminogen activator inhibitor, fibrin stimulation of plasminogenolytic activity and/or enhanced affinity to fibrin surfaces are provided by modifying one or more loci by deletions or substitutions. One or both of the N- or C-termini may be modified.

公开(公告)号：US4818690A

公开(公告)日：1989-04-04

申请号：US849717

申请日：1986-04-09

申请人： Eric P. Paques

发明人： Eric P. Paques

IPC分类号： C12Q1/37 ,  C12Q1/56 ,  G01N33/86

CPC分类号： C12Q1/56 ,  C12Q2337/12 ,  G01N2333/968 ,  G01N2333/9723 ,  G01N2333/9726 ,  G01N2400/40

摘要： A method for the determination of urokinase (UK) or tissue plasminogen activator (t-PA) is described, in which the activator is incubated with plasminogen, with a polysulfuric ester of a saccharide or with a sulfated sugar and, where appropriate, fibrin or fibrin degradation products, and the conversion of plasminogen into plasmin is determined, and agents suitable for this method are described.

摘要翻译： 描述了用于测定尿激酶（UK）或组织纤溶酶原激活物（t-PA）的方法，其中将活化剂与纤溶酶原与多糖或硫酸化糖的合成物和适当的纤维蛋白或 纤维蛋白降解产物和纤溶酶原转化成纤溶酶，并描述适合于该方法的试剂。

公开(公告)号：US5202416A

公开(公告)日：1993-04-13

申请号：US392072

申请日：1989-08-10

申请人： Werner Stuber ,  Eric P. Paques

发明人： Werner Stuber ,  Eric P. Paques

IPC分类号： C07K1/00 ,  C07K1/113 ,  C07K1/22 ,  C07K5/06 ,  C07K5/062 ,  C07K5/08 ,  C07K17/02 ,  C07K17/08 ,  C07K17/10 ,  C08F8/00 ,  C08G59/52 ,  C12N9/64 ,  C12N9/72

CPC分类号： C12N9/6424 ,  C07K17/02 ,  C07K5/06043 ,  C12N9/6456

摘要： Peptide derivatives of the Formula IR--Y--Leu--Pro--NH--CH(CH.sub.2 --CH.sub.2 --CH.sub.2 --NH--C(.dbd.NH)--NH.sub.2)--Xin which Y is HN--(CH.sub.2).sub.n --CO with n=1 to 8 or a bond, X is CN, CH.sub.2 OH or CHO and R is a support or a hydrogen atom, a process for the preparation thereof, and the use thereof for affinity chromatography, especially for isolating and purifying proteases, are described.

摘要翻译： 式I RY-Leu-Pro-NH-CH（CH 2 -CH 2 -CH 2 -NH-C（= NH）-NH 2）-X的肽衍生物，其中Y是HN-（CH 2）n -CO，n = 1 至8或键，X为CN，CH 2 OH或CHO，R为支链或氢原子，其制备方法及其用于亲和层析，特别是用于分离和纯化蛋白酶的用途。

公开(公告)号：US5049545A

公开(公告)日：1991-09-17

申请号：US323156

申请日：1989-03-15

申请人： Hartmut Lobermann ,  Eric P. Paques ,  Norbert Heimburger

发明人： Hartmut Lobermann ,  Eric P. Paques ,  Norbert Heimburger

IPC分类号： C07K14/575 ,  A61K38/00 ,  A61K38/28 ,  A61P3/08 ,  C07K1/06 ,  C07K1/113 ,  C07K14/62 ,  C07K14/76 ,  C07K14/81 ,  C07K19/00

CPC分类号： C07K14/62 ,  A61K38/00

摘要： Insulin derivatives of the general formulae I and IIX--(Y.sub.1 --S--S--Y.sub.2 --Z--"Insulin").sub.m IA--S--Y.sub.3 --Z--"Insulin" IIin whichX is a radical of a physiologically tolerated carbon compound,Y.sub.1, Y.sub.2 and Y.sub.3 are, independently of one another, a chemical bond or an organic chemical bridge,S is a sulfur atom,"Insulin" denotes the biologically active peptidic portion of a natural, semisynthetic or synthetic insulin or an insulin which has been prepared by genetic engineering, or one of its biologically active analogs without the inessential amino group,Z is an amino group which is inessential for the biological activity of insulin,A is a hydrogen atom or the radical of a mercapto-containing, physiologically tolerated hydrocarbon compound, andm is an integer from 1 to 20,agents containing these derivatives, a process for the preparation of these derivatives, and their use for the treatment of metabolic disorders, are described.

摘要翻译： 通式I和II的胰岛素衍生物X-（Y1-SS-Y2-Z-“胰岛素”）m I AS-Y3-Z-“胰岛素”II，其中X是生理耐受性碳化合物的基团，Y1 ，Y2和Y3彼此独立地是化学键或有机化学桥，S是硫原子，“胰岛素”表示已经制备的天然的，半合成的或合成的胰岛素或胰岛素的生物活性肽部分 通过遗传工程，或其生物活性类似物之一，其中没有非必需氨基，Z是对胰岛素生物活性无关的氨基，A是氢原子或含巯基的生理耐受性烃化合物 ，m为1〜20的整数，含有这些衍生物的试剂，这些衍生物的制备方法及其用于治疗代谢紊乱的用途。

公开(公告)号：US5015583A

公开(公告)日：1991-05-14

申请号：US282906

申请日：1988-12-12

申请人： Eric P. Paques

发明人： Eric P. Paques

IPC分类号： A61K38/46 ,  A61K35/12 ,  C12N9/64 ,  C12N9/72

CPC分类号： C12N9/6456 ,  Y10S435/814 ,  Y10S435/948

摘要： A process is described for the purification of plasminogen activator (PA), wherein a solution containing such as plasminogen activator is brought into contact with a carrier-bound polysulfate of a saccharide or sulfated sugar, the liquid is removed, and the PA bound by this material is eluted.

摘要翻译： 描述了用于纯化纤溶酶原激活物（PA）的方法，其中使含有诸如纤溶酶原激活剂的溶液与糖或硫酸化糖的载体结合的多硫酸盐接触，除去液体，并且通过该方法结合PA 材料被洗脱。

公开(公告)号：US4621631A

公开(公告)日：1986-11-11

申请号：US564917

申请日：1983-12-23

申请人： Eric P. Paques ,  Peter Fuhge

发明人： Eric P. Paques ,  Peter Fuhge

IPC分类号： A61L15/16 ,  A61L15/20 ,  A61L15/32 ,  C08J5/18 ,  C09H3/00 ,  C09H7/00 ,  A61F13/00

CPC分类号： C09H7/00 ,  A61L15/20 ,  A61L15/325 ,  C09H3/00 ,  Y10S128/08 ,  Y10S514/801

摘要： A process for the production of an unnative and biologically active bonded collagen fiber sheet from human placentae is described, in which process collagen-containing material from placentae is treated with a neutral salt solution, a solution of citric acid and with pepsin. The degraded collagen material obtained in this manner is, where appropriate, treated with a crosslinking agent. The collagen material produced in this manner is used for producing bonded collagen fiber sheets which can be used, for example, as covering for wounds.

摘要翻译： 描述了从人胎盘生产不需要的和生物活性的粘合的胶原纤维片的方法，其中使用中性盐溶液，柠檬酸溶液和胃蛋白酶处理来自胎盘的含胶原物质。 以这种方式获得的降解胶原材料在适当的情况下用交联剂处理。 以这种方式制造的胶原材料用于生产可用于例如伤口覆盖物的粘合胶原纤维片。