Takeda T, Yoshino K, Adachi E, Yamagata K, Uchida H, Okonogi K, Iizawa Y
TAKEDA Chemical Industries, Ltd., Pharmacology Laboratories, Pharmaceutical Research Division.
Kansenshogaku Zasshi. 1998 Sep;72(9):924-34. doi: 10.11150/kansenshogakuzasshi1970.72.924.
TAK-751S is a synthetic trisaccharide coupled to Chromosorb P using a spacer sequence of 8-methoxycarboyloctyl (MCO). Its chemical structure is similar to a human receptor (Gb3) of Stx produced by enterohemorrhagic Escherichia coli (EHEC). In vitro efficacy of TAK-715S was studied by using ACHN cultured cell assay, which is sensitive and specific for measuring low level of Stx. Under various conditions, TAK-715S was mixed with purified Stx1 and Stx2, and residual free toxins in the solution were measured by using ACHN cells. TAK-715S was demonstrated to bind specifically to Stx1 and Stx2 under the condition similar to a human intestine while Chromsorb P did not bind to any Stx. The binding activity was stable in the presence of various processed foods, fresh vegetables and fruits. Antibiotics such as fosfomycin, kanamycin and norfloxacin did not disturb its binding capability. Minimum inhibitory concentrations of these antibiotics against Staphylococcus aureus FDA209P or E. coli NIHJ JC-2 neither changed after incubating with TAK-751S for 60 min at 37 degrees C. These results suggest that TAK-751S can be given orally with various foods and antibiotics for the elimination of Stx1 and Stx2 in the gut of patients with EHEC infections.
TAK - 751S是一种合成三糖,通过8 - 甲氧基羰基辛基(MCO)的间隔序列与Chromosorb P偶联。其化学结构类似于肠出血性大肠杆菌(EHEC)产生的志贺毒素(Stx)的人类受体(Gb3)。通过使用ACHN培养细胞测定法研究了TAK - 715S的体外功效,该方法对测量低水平的Stx敏感且特异。在各种条件下,将TAK - 715S与纯化的Stx1和Stx2混合,并使用ACHN细胞测量溶液中残留的游离毒素。在类似于人类肠道的条件下,TAK - 715S被证明能特异性结合Stx1和Stx2,而Chromsorb P不与任何Stx结合。在存在各种加工食品、新鲜蔬菜和水果的情况下,结合活性稳定。磷霉素、卡那霉素和诺氟沙星等抗生素不会干扰其结合能力。在37℃下与TAK - 751S孵育60分钟后,这些抗生素对金黄色葡萄球菌FDA209P或大肠杆菌NIHJ JC - 2的最低抑菌浓度均未改变。这些结果表明,TAK - 751S可以与各种食物和抗生素一起口服,以消除EHEC感染患者肠道中的Stx1和Stx2。