首页> 外国专利> OLIGOPEPTIDE SELECTIVELY INHIBITING THE GROWTH OR MULTIPLICATION OF NORMAL AND LEUKAEMIC MYELOID CELLS, TO BE ISOLATED FROM HEALTHY WHITE BLOOD CELLS OR GRANULOCYTES, PROCESS FOR ITS PREPARATION, AND MEDICAMENTS CONTAINING IT

OLIGOPEPTIDE SELECTIVELY INHIBITING THE GROWTH OR MULTIPLICATION OF NORMAL AND LEUKAEMIC MYELOID CELLS, TO BE ISOLATED FROM HEALTHY WHITE BLOOD CELLS OR GRANULOCYTES, PROCESS FOR ITS PREPARATION, AND MEDICAMENTS CONTAINING IT

机译:寡肽选择性抑制正常和白血病骨髓细胞的生长或繁殖,这些细胞将从健康的白血细胞或颗粒细胞,其制备过程以及包含该药物的药物中分离出来

摘要

For the Contracting States : BE, CH, DE, FR, GB, IT, LI, NL, SE 1. Oligopeptide isolable from sound erythrocytes or granulocytes, respectively, selectively inhibiting the growth or proliferation, respectively, of normal and leukemic myeloid cells, characterized in that it has the gross amino acid composition Tau1 , Asx1 , Ser2 , Thr1 , Glx3 , Gly2 , Ala1 , (PO4 )1 in which Tau represents a radical of taurine, Asx means a radical of L-asparagin and/or L-asparaginic acid, Ser represents a radical of L-serine, Thr means a radical of L-threonine, Glx represents a radical of L-glutamine and/or L-glutamic acid, Gly means a radical of glycine and Ala represents a radical of L-alanine and exhibits at a pH-value of 6.5 a negative charge and a relative electrophoretic mobility of from -0.55 to -0.65 referred to asparaginic acid or at a pH-value of 1.9 no charge and a relative mobility of about 0.26 referred to epsilon-(dinitrophenyl)-lysine and has a positive reaction to chlorotolidine. For the Contracting State : AT 1. A process for preparing an oligopeptide isolable from sound erythrocytes or granulocytes, respectively, selectively inhibiting the growth or proliferation, respectively, of normal and leukemic myeloid cells having the gross amino acid composition Tau1 , Asx1 , Ser2 , Thr1 , Glx3 , Gly2 , Ala1 , (PO4 )1 in which Tau represents a radical of taurine, Asx means a radical of L-asparagin and/or L-asparaginic acid, Ser represents a radical of L-serine, Thr means a radical of L-threonine, Glx represents a radical of L-glutamine and/or L-glutamic acid, Gly means a radical of glycine and Ala represents a radical of L-alanine and exhibits at a pH-value of 6.5 a negative charge and a relative electrophoretic mobility of from -0.55 to -0.65 referred to asparaginic acid or at a pH-value of 1.9 no charge and a relative mobility of about 0.26 referred to epsilon-(dinitrophenyl)-lysine and having a positive reaction to chlorotolidine, characterized in that one a) homogenises sound erythrocytes gained from animal or human blood, particularly horse blood, in a buffer solution having a pH-value of from 7 to 8, one centrifuges the liquid homogenisate, one separates from the supernantant liquid the dissolved components having molecular weights below 10 000, one subjects this fraction to a further fractionation, suitably by gel chromatography, and separates the fraction precipitating at volume values ve /vo of from 1.15 to 1.45 and optionally lyophilises it or b) homogenises animal organs containing granulocytes, particularly calf spleen, in an organic solvent miscible with water, one separates from the obtained liquid suspension the solids and extracts them with an organic solvent dissolving fats, one extracts the thus obtained solids with water, one separates from the liquid suspension obtained the insoluble part and one separates from the liquid phase the dissolved components having molecular weights below 10 000, one subjects this fractions to a further fractionation, suitably by gel chromatography, and one separates the fraction precipitating at volume values ve /vo of from 1.3 to 2.5 and optionally lyophilises and one purifies the concentrate of active principle obtained according to one of the above variants a) and b) by chromatographing fractionating on account of the ionic charge and particle size and/or by paper-electrophoresis and one separates the oligopeptide having at a pH-value of 6.5 a negative charge and a relative mobility of from -0.55 to -0.65 referred to asparaginic acid or exhibiting at a pH-value of 1.9 no charge and a relative mobility of about 0.26 referred to epsilon-(dinitrophenyl)-lysine, respectively and positively reacting to chlorotolidine and optionally lyophilises it.
机译:对于缔约国:BE,CH,DE,FR,GB,IT,LI,NL,SE1。寡肽分别可从健全的红血球或粒细胞中分离出来,分别选择性地抑制正常和白血病髓样细胞的生长或增殖,其特征在于其具有总氨基酸组成Tau1,Asx1,Ser2,Thr1,Glx3,Gly2,Ala1,(PO4)1,其中Tau代表牛磺酸的基团,Asx表示L-天冬酰胺和/或L-的基团天门冬氨酸,Ser代表L-丝氨酸的基团,Thr代表L-苏氨酸的基团,Glx代表L-谷氨酰胺和/或L-谷氨酸的基团,Gly代表甘氨酸的基团,Ala代表L的基团-丙氨酸,在pH值为6.5时表现出负电荷,相对电泳迁移率为-0.55至-0.65(相对于天冬酰胺酸),在pH值为1.9时,无电荷,相对迁移率约为0.26(对于ε) -(二硝基苯基)-赖氨酸,对氯甲苯啶呈阳性反应。对于缔约国:AT 1.一种可分别从健全的红血球或粒细胞分离的寡肽的制备方法,分别选择性地抑制具有总氨基酸组成Tau1,Asx1,Ser2的正常和白血病髓样细胞的生长或增殖。 Thr1,Glx3,Gly2,Ala1,(PO4)1,其中Tau代表牛磺酸基团,Asx代表L-天冬酰胺和/或L-天冬酰胺酸基团,Ser代表L-丝氨酸基团,Thr代表基团在L-苏氨酸中,Glx代表L-谷氨酰胺和/或L-谷氨酸的基团,Gly代表甘氨酸的基团,Ala代表L-丙氨酸的基团,并且在pH值为6.5时具有负电荷和相对电迁移率为-0.55至-0.65(相对于天冬酰胺酸而言),或者在pH值为1.9时不带电荷,相对迁移率约为0.26(相对于ε-(二硝基苯基)-赖氨酸),并且对氯甲苯啶呈阳性反应,其特征在于一个a)同性恋在pH值为7至8的缓冲溶液中稀释从动物或人类血液,特别是马血中获得的健全红血球,一将液体匀浆离心,一从上清液中分离出分子量低于10000的溶解成分,适当地通过凝胶色谱法,对该级分进行进一步的分级,并分离出以1.15至1.45的体积值ve / vo沉淀的级分,并任选地冻干它;或b)将含有粒细胞,特别是小牛脾脏的动物器官均质化。与水混溶的有机溶剂,一种从所得液体悬浮液中分离出固体,并用溶解脂肪的有机溶剂萃取,一种用水萃取所得固体,一种从液体悬浮液中分离出不溶部分,另一种与液体分离。将分子量低于10000的溶解组分进行分相,使这一馏分发生糠fur她的分级分离,适当地通过凝胶色谱法进行,并且分离以1.3至2.5的体积值ve / vo沉淀的级分,并任选冻干,并且一种通过以下方法纯化根据上述变体a)和b)之一获得的活性成分的浓缩物根据离子电荷和颗粒大小和/或通过纸电泳进行色谱分离,然后分离出在pH值为6.5时带有负电荷且相对迁移率为-0.55至-0.65的寡肽,称为天冬酰胺酸或在1.9的pH值下显示出无电荷并且相对于ε-(二硝基苯基)-赖氨酸的相对迁移率分别为约0.26,并且与氯代甲苯胺正反应并任选冻干。

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