STUDYING THE ACUTE TOXICITY AND ANTI-TUMOR ACTIVITY OF THE NEW DRUG COLHAMETIN

Yuldashev Javlonabduraimovich, Ibragimov Shavkat Narzikulovich, Shakhanova Shakhnoza Shavkatovna, Esankulova Bustonoy Sobirovna
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Abstract

The aim of the study was to study acute toxicity during intraperitoneal administration of a new antitumor drug "colhametin" (K-2) in mice and rats and its antitumor activity on 2 strains of tumors, including with a smaller number of injections. Material and research methods. Acute toxicity of the K-2 preparation after a single intraperitoneal injection was carried out according to the Litchfield and Wilcoxon method on 30 white outbred mice weighing 20±2g of both sexes and 30 male and female rats weighing 140±10g, 5 animals in each group. The study of antitumor activity was performed on 12 outbred mice and 16 outbred rats with transplanted tumors S-180 (Sarcoma-180) and WC (Walker's sarcoma) which were administered drugs on the 4th day after tumor inoculation 10- and 5-fold. The results were evaluated according to standard criteria: tumor growth inhibition (TGI), body weight and spleen of animals Differences were considered significant at p<0.05. Results. The following data were obtained with a single intraperitoneal injection to mice: the average lethal dose of LD50 is 890 (-150 + 172) mg/kg, LD50 with a single intraperitoneal dose of K-2 preparation in rats, LD50 is 410 (-56 + 61) mg/kg, the values are also determined LD10, LD16 and LD84. The antitumor activity of the drug K-2 on the tumor strain Sarcoma - 180 was high, 99/90%. On WC tumors the effect of K-2 reached 90/91% with 10-fold administration, and 89/89% with 5-fold administration, however, its effect was accompanied by a decrease in hematopoietic parameters. Conclusions. The study of the acute toxicity of the substance of the preparation K-2 showed that this preparation belongs to the IV class of low-toxic compounds. On 2 tumors, the effect of the new drug was high, which did not decrease with a decrease in the number of injections.
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研究了新药物胭脂虫素的急性毒性和抗肿瘤活性
本研究旨在研究新型抗肿瘤药物“colhametin”(K-2)腹腔注射对小鼠和大鼠的急性毒性及对2种肿瘤的抗肿瘤活性,包括少量注射。材料和研究方法。采用Litchfield和Wilcoxon法,对30只体重为20±2g的雌雄纯种小白鼠和30只体重为140±10g的雌雄大鼠,每组5只进行K-2制剂单次腹腔注射后的急性毒性实验。对移植瘤S-180 (sarcoma -180)和WC (Walker's sarcoma)的12只远交系小鼠和16只远交系大鼠在肿瘤接种后第4天分别给予10倍和5倍的药物,研究其抗肿瘤活性。按标准标准对结果进行评价:肿瘤生长抑制(TGI)、动物体重、脾脏以p<0.05为差异有统计学意义。结果。小鼠单次腹腔注射的LD50平均致死剂量为890 (-150 + 172)mg/kg,大鼠单次腹腔注射K-2制剂的LD50平均致死剂量为410 (-56 + 61)mg/kg,并测定LD10、LD16和LD84的值。药物K-2对肿瘤株Sarcoma - 180的抗肿瘤活性较高,为99/90%。K-2对WC肿瘤10次给药的效果为90/91%,5次给药的效果为89/89%,但其作用伴随着造血参数的降低。结论。对制剂K-2所含物质的急性毒性研究表明,该制剂属于IV类低毒化合物。2种肿瘤的疗效较高,且不随注射次数的减少而降低。
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