Доклиническое исследование общей токсичности Препарат «Фитин-С»

Аннотация

A pre-clinical study of the general toxicity of the medication “Fitin-S” has shown that it is referred to class IV of low toxic compounds. The medication “Fitin-S” does not have aaccumulative and local irritant action. At multiple intramuscular administration to rats and rabbits it does not influence the behavior and the dynamics of animals growth, does not cause a toxic effect on the composition of peripheral blood, kidneys’ and liver’s function as well as on the pathomorphology of animals organs and tissues. There is a slowdown in the process of blood coagulation in rabbits at doses of 16 and 32 mg/kg during the whole study period. In 1 month of a recovery period all the indicators have been changing within physiological norm. All the aforementioned data allows us to make a conclusion that the medication does not cause a toxic effect on the organism of animals. Keywords: General toxicity, medication “Fitin-S”, acute toxicity, cumulation, chronic toxicity, local irritant action, pathomorphological study. Introduction solution of the medication tested. The trials have been performed on 10 mice of both sexes weighing 20±2.0 g. The The purpose of studying the medication “Fitin-S” is to medications have been administered intramuscularly establish the nature and severity of its damaging effects on according to the scheme for 24 days from 0.1 to 1.15 from the body of experimental animals and assess its safety. LD 4. 50 Materials and Method The general toxic action of “Fitin-S” at multiple intramuscular administration has been studied in 40 non- The study of acute toxicity of the medicationshas been linear white rats (males and females) with the initial weight carried out according to the method of Litchfield and of 110±10 grams and in 16 gray-colored rabbits of both Wilcoxon on white mice, both sexes, weighing 20±2.0 g of sexes with the initial weight 2,0±0,2 kilograms. Animals 6 animals in each group, 150 mice has been used in total2. were in vivarium on a normal diet. The trial animals have All pharmacological studies have been performed on healthy been divided into 4 groups: 10 rats (5 males and 5 females) sexually mature animals (mice) exposed to the quarantine of at least 10-14 days1. and 4 rabbits (2 females and 2 males) in each. The medication has been administered intramuscularly daily (7 The medication tested has been injected intravenously, days a week) for 30 days to rats at doses of 20, 40 and 100 subcutaneously and intramuscularly as a single dose of 100 mg/kg and to rabbits at 8.0, 16.0 and 40 mg/kg. The control to 10000 mg/kg. The animals were monitored hourly during animals have been 1218 Medico-legal Update, October-December the first day of the experiment in the laboratory, while the 2020, Vol. 20, No. 4 injected with distilled water in a survival rate during the experiment, general condition, bioequivalent volume. All animals have been kept in possible convulsions and death were used as indicators of standard vivarium conditions on a full-fledged food and the functional state of the animals. At the end of the water diet. experiment, the average lethal dose (LD50) has been calculated and the toxicity class has been determined3. The The condition of animals during chronic intramuscular study of accumulation of “Fitin-S” has been carried out administration has been evaluated by the following according to the Lim’s method, which allows to evaluate not parameters of peripheral blood: haemoglobin contents, gr/dl; the number of red blood cells,1012/l; reticulocytes,% ; only accumulation, but also addiction. The objective of the 0 thrombocytes, 109/l; leucocytes, 109/ land leukogram; liver study was to identify a possible accumulative property in the function evaluation - by glucose content,mmol/1; total studied on 12 rats weighed 150±10 grams. The animals have protein,gr/dl; alanine - and aspartate - aminotransferases had their hair clipped on both sides of the spinal column (4 (A1AT, AsAT) in blood serum. Biochemical tests have been areas) 2x2 cm in size.0,5 ml of Fitin-S in 0,5 and 5% performed using test kits from CypressDiagnostica, solutions have been applied on two clipped areas on the left Belgium. Renal function has beenevaluated by dimesis with side of the back. The medication has been applied for 10 a water load (5% of body weight) for 4 hours, blood urea, days. The controlled areas were the right clipped areas to urine acidity (pH), the presence of nitrites, glucose, which distilled water has been applied in the same volume. leukocytes etc. in the urine (qualitative reactions) with the The monitoring has been carried out for 14 days. The skin Combina kit, Germany, and by urinary sediment. reaction has been recorded daily according to the skin sample scale in points8. Hematological and biochemical studies were performed after 10 and 30 days post the day of the experiment. At that Statistical processing of the obtained data has been time animals were weighed. At the end of the experiment car