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Pseudolycorine is an alkaloid isolated from Narcissus tazetta var. chinensis Roem, N. papyraceus or Lycoris radiata Herb. Both the free alkaloid and its hydrochloride showed marked inhibition on the growth of W-256 carcinosarcoma in rats under tolerable doses, but the inhibition on the growth of hepatoma, subcutaneous transplants of Ehrlich ascites cascinoma and S-180 in mice was not significant. The LD_(50) of pseudolycorine injected intraperitoneally to rats was found to be 110(92.4~131)mg/kg. Intraveneous... Pseudolycorine is an alkaloid isolated from Narcissus tazetta var. chinensis Roem, N. papyraceus or Lycoris radiata Herb. Both the free alkaloid and its hydrochloride showed marked inhibition on the growth of W-256 carcinosarcoma in rats under tolerable doses, but the inhibition on the growth of hepatoma, subcutaneous transplants of Ehrlich ascites cascinoma and S-180 in mice was not significant. The LD_(50) of pseudolycorine injected intraperitoneally to rats was found to be 110(92.4~131)mg/kg. Intraveneous infusion of the drug caused slow lowering of the blood pressure in the cat, but the dose of the drug required to kill the cat is rather high (av. 881mg/kg). The subacute toxicity tests in the dogs showed that pseudolycorine may induce nausea, vomiting and anorexia, but it did not inhibit the bone marrow significantly. Some increase of the nonprotein nitrogen value in the dogs after adminstration of the drug was observed, but this might be caused by prerenal factors. Autopsy of the dogs showed no significant pathological changes in the viscera, including the heart, liver, spleen, lung, kidney and intestine. Phase I clinical trial of the drug is now in progress. 伪石蒜硷是从石蒜科植物水仙及石蒜中提得的生物硷。其游离硷及盐酸盐在动物耐受剂量下,对大鼠W-256的生长有明显的抑制作用,抑制率在49~76%之间,统计学上差异非常显著。对小鼠肝癌、艾氏腹水癌皮下型、S-180的抑制作用不明显。已测得伪石蒜硷对大鼠一次腹腔注射的LD_(50)为110(92.4~131)mg/kg。对猫静脉滴注可致缓慢血压下降,滴注致死要求很大剂量(平均881mg/kg)。根据推算现在的病人试用剂量(~1mg/kg/日)是安全的。狗的亚急性毒性试验表明,此药可引起恶心、呕吐、厌食,但对骨髓无明显抑制作用。用药后曾见血中非蛋白氮值上升,考虑为肾前因素引起。病理解剖心、肝、脾、肺、肾、肠各脏器均未见明显病变。药物正开始进行Ⅰ期临床试用中。 In this paper the subacute toxicity of the new photosensitizer FSD-007 in dogs is reported. The manifestations of its subacute toxicity such as salivation, nausea, vomi-tus and other early syndromes were similar to those of porphyrinemia. The laboratory findings showed that the red cell system was depressed markedly, and hepatic and renal functions were impaired to some extent. These lesions were reversible and coincident with what was observed in its acute toxicity. The experimental results have further provided... In this paper the subacute toxicity of the new photosensitizer FSD-007 in dogs is reported. The manifestations of its subacute toxicity such as salivation, nausea, vomi-tus and other early syndromes were similar to those of porphyrinemia. The laboratory findings showed that the red cell system was depressed markedly, and hepatic and renal functions were impaired to some extent. These lesions were reversible and coincident with what was observed in its acute toxicity. The experimental results have further provided the evidence that these may be used clinically fer guard against its toxic effects.The results of phase I of clinical pharmacological study of FSD-007 have shown that there were no toxic effects observed after 2.5-5.0mg/kg iv on condition that the patient were kept away from direct sunlight for a month. And its subacute toxieity test has demonstrated that all its toxic changes arc dose-related,reversible and predictable. This preparation, therefore, may be safely tested in phase II with same dosage, but no duplicate administration is permitted within two weeks. 本文报道肿瘤诊治新光敏剂PSD-007对狗的亚急性毒性。亚急性毒性的表现举如流涎、恶心、呕吐及其他早期症群与血卟啉病相似,实验室检查可见血液红系统的抑制,以及肝、肾功能的一定程度的损害,均属可逆反应,并与急性毒性相一致,进一步证实这些可作为PSD-007临床试用中的监护指标。 鉴于PSD-007第一期临床试验的结果表明,一次静注2.5~5.0mg/kg后在避免日光直接照射一个月的情况下,未出现包括光毒在内的任何毒副反应;而亚急性毒性试验又证实其毒性是可逆的,并与剂量平行,且可预测,故本制剂以相同剂量在不短于两周内重复给药可安全地开展第二期临床试验。 In order to clinically differentiate the pulmonary hypertention stage and the heart failure stage in infants with pneumonia, RPEP/RVET and RPEP/T were used as an objective standard for observing the clinical manifestations of these two stages. Many different clinical features were found which would help the physician to select a suitable time to use vasodilator drugs. 本文采用肺阻抗微分图时相分析法测量RPEP/RVET和RPEP/T两个比值以区别婴幼儿肺炎肺动脉高压期和心衰期。然后再以此两个比值作为客观指标观察心衰期及肺动脉高压期的临床表现,提出临床上的判断标准及何时需用血管扩张药。
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