van Ramshorst J D, Sundaresan T K
Bull World Health Organ. 1972;46(1):53-66.
An international collaborative assay was performed with the aim of establishing an international standard for tetanus toxoid (adsorbed). Six laboratories participated. A suitable preparation in the lyophilized state was made available by the Paul Ehrlich Institut, Frankfurt am Main, Federal Republic of Germany. Preliminary experiments showed that there were no significant differences between individual ampoules and that the preparation was highly thermostable.The proposed preparation (A) was compared in guinea-pigs and mice with the existing international standard for tetanus toxoid (B), which is a plain toxoid, with another arbitrarily chosen adsorbed toxoid (C), and with a number of locally prepared preparations (D). In the mouse tests preparation B was omitted. It was found in the guinea-pig tests that 1 mg of the proposed standard contained an activity equivalent to 1.5 IU if compared with the non-adsorbed international standard but since the slopes of the log dose-response lines for the adsorbed and plain types of preparation were not parallel, this is a rough approximation only. When the different adsorbed preparations were compared, there was close correlation between the guinea-pig tests and the mouse tests. In the guinea-pig test 1 ml of preparation C corresponded to 126.5 mg of preparation A and in the mouse test to 129.9 mg of preparation A. In one laboratory comparative tests were made by titrating blood antitoxins after immunization of guinea-pigs with graded doses of the toxoids. The results corresponded very well with the data from challenge tests (1 mg of preparation A contained 1.5 IU of the plain toxoid in challenge tests and|1.4 IU in the titration test).Preparation A was established by the WHO Expert Committee on Biological Standardization as the international standard for tetanus toxoid (adsorbed) and the international unit was defined as the activity contained in 0.6667 mg of the international standard.
为了建立吸附破伤风类毒素的国际标准，进行了一项国际协作试验。六个实验室参与其中。德国联邦共和国美因河畔法兰克福的保罗·埃利希研究所提供了一种合适的冻干制剂。初步实验表明，各个安瓿之间没有显著差异，并且该制剂具有很高的热稳定性。将提议的制剂（A）在豚鼠和小鼠中与破伤风类毒素的现有国际标准（B，一种普通类毒素）、另一种任意选择的吸附类毒素（C）以及一些当地制备的制剂（D）进行比较。在小鼠试验中省略了制剂B。在豚鼠试验中发现，如果与非吸附国际标准相比，1毫克提议的标准制剂所含活性相当于1.5国际单位，但由于吸附型和普通型制剂的对数剂量反应线斜率不平行，这只是一个粗略的近似值。当比较不同的吸附制剂时，豚鼠试验和小鼠试验之间有密切的相关性。在豚鼠试验中，1毫升制剂C相当于126.5毫克制剂A，在小鼠试验中相当于129.9毫克制剂A。在一个实验室中，用不同剂量的类毒素免疫豚鼠后，通过滴定血液抗毒素进行了比较试验。结果与攻击试验的数据非常吻合（在攻击试验中，1毫克制剂A含有1.5国际单位的普通类毒素，在滴定试验中为1.4国际单位）。世界卫生组织生物标准化专家委员会将制剂A确立为吸附破伤风类毒素的国际标准，并将国际单位定义为0.6667毫克国际标准制剂所含的活性。
