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本文研究了17种磷酰胺氮芥类化合物,发現N-双(2-氯乙基)-N’-N"-二乙撐基磷酰胺(以下均簡称AT-222)具有較强的抗癌作用。主要結果如下:(1)腹腔注射AT-2221—2.5毫克/公斤对小白鼠肉瘤180,网織細胞肉瘤,AK肉瘤,梭形細胞肉瘤,大白鼠Jensen肉瘤和Walker癌肉瘤都有明显的抑制作用,口服給药时对Jensen肉瘤也有一定的疗效。但对Ehrlish癌固体型和腹水型則无明显的影响。(2)AT-222对小白鼠的急性和亚急性LD_(50)分別为19和4.7毫克/公斤,大白鼠的亚急性LD_(50)为2.7毫克/公斤(停药后观察3天)和1.9毫克/公斤(停药后观察10天)。(3)給狗靜脉注射AT-222 0.1毫克/公斤,其血象、大小便和体重均无明显改变。在0.3毫克/公斤組,給药第5天时白血球稍有下降,停药后逐渐恢复,解剖发現腸粘膜有出血点,脾淋巴細胞核和卵巢顆粒細胞核有固縮現象。0.9毫克/公斤組,于給药后第5天时白血球卽明显下降,停药后2—4天动物相继死亡,解剖检查发现各脏器均有弥蔓性出血,腸、胃腺体、腎上腺和睾丸均有明显萎縮。
In this paper, 17 kinds of phosphoramidate mustard compounds were studied. It was found that N-bis (2-chloroethyl) -N’-N’-diethylphosphonamide (hereinafter referred to as AT-222) The main results are as follows: (1) AT-2221-2.5 mg / kg was injected intraperitoneally to all mice with sarcoma 180, reticulocyte sarcoma, AK sarcoma, spindle cell sarcoma, rat Jensen sarcoma and Walker carcinosarcoma There was a significant inhibitory effect on oral administration of Jensen sarcoma have a certain effect, but Ehrlish cancer solid ascites and type had no significant effect. (2) AT-222 in mice acute and subacute LD 50 ) Were 19 and 4.7 mg / kg, respectively, and the subacute LD 50 of rats was 2.7 mg / kg (observed for 3 days after discontinuation) and 1.9 mg / kg (observed for 10 days after discontinuation). (3) Dogs intravenous injection of AT-222 0.1 mg / kg, blood, urine and body weight were no significant changes in the 0.3 mg / kg group, the fifth day after administration of white blood cells decreased slightly, gradually recovered after withdrawal, anatomical findings intestine Mucosal bleed points, spleen lymphocyte nuclei and ovarian granulosa cells with shrinkage phenomenon .0.9 mg / kg group, on the 5th day after administration of leukocyte significantly decreased, stop Animals 2-4 days after the animals were killed, anatomical examination found that all organs were diffuse bleeding, intestinal, gastric glands, adrenal and testicular were significantly atrophy.