Zhyla M. Pharmacological and clinicomorphological evaluation of immunomodulatory and probiotic agents (clinical trials, documentation, pharmacological examination of the effectiveness of action)

The thesis presents the results of pharmacological, toxicological and morphological assessment of the efficacy and safety of probiotic feed additive «Probion-forte» and the new veterinary pharmaceutical products with immunomodulatory effect «Bioton», with clinical trials on the target animals. The proposed science-based system of clinical trials that includes order, inventory, processing and approval of the documentation, subject to the requirements of Good Clinical Practice and international standards. The indicators of the quality and stability of probiotic feed additive «Probion-forte» were identified and the parameters of safety for a single intragastric administration to white mice in a dose of 5000 mg/kg body weight and tolerance for chickens-broilers in a dose 10 and 100 times higher than recommended. It is proved that the use of food additives «Probe-Forte» for chickens-broilers during the whole growing period and the piglets – 70 days after weaning, improved digestibility, increased productivity and a positive impact on intestinal microflora. Morphometrics in the immune organs the increase in area and density of lymphoid cells, growth in the number of plasmoblasts, plasma cells and higher functional activity, which was reflected at the ultrastructural level. The parameters of toxicity «Bioton» for white mice and rats, which attributed to the 4 th class of low-toxic substances. When applying «Bioton» to rats in a therapeutic dose the stimulation of the immune defense on 15 and 30 day is established. Long-term use (60 days) caused negative changes in blood parameters and pathological processes in internal organs of rats. Watering turkeys with drug «Bioton» in a dose of 1.0 and 2.0 ml/l during 7 days with repetition rate of 6, 15, 21 week, contributed to the improvement of metabolic processes, nonspecific resistance, humoral immunity, reflected by the increase of safety stock, increasing body weight and slaughter yield of carcasses. Histomorphometrical is noticed the slow process of age involution of the thymus and cloacal bursa in comparison with the control group.