Onyshchuk L. Experimental justification for the development of drug for intravaginal use with anti-inflammatory and antimicrobial activity

The thesis is dedicated for the development of drug for intravaginal use with anti-inflammatory and antimicrobial activity. In the dissertation, based on the study of the antimicrobial effect of the components of MC 1 – MC-15 samples, for the first time the leader-MCI– 4 (metronidazole 100 mg, clotrimazole 400 mg and ibuprofen 80 mg). New data on the safety of the MCI-4 combination have been obtained. It is proved that it belongs to grade V toxicity "Practically non-toxic compounds" when administered intragastrally. When using MCI-4 in doses of 9.42 mg/kg, 94.2 mg/kg and 942 mg/kg for 3 months, no toxic effect on behavioral reactions, body weight and internal organs, indicators of the functional state of the liver and kidneys was established. For the first time, morphometry proved a positive effect of MCI-4 at a dose of 53 mg/kg on the vaginal epithelial plate and a decrease in the sum of points that characterize the degree of the pathological process to 4 compared to TV 8 (P<0.05) when modeling TV, AV in rats. The positive effect of MCI-4 on the functional parameters of peripheral blood leukocytes, namely their redistribution, phagocyte index, and phagocyte number of the studied samples in vivo on TV and AV models, was established. It is confirmed that vaginitis of mixed etiology is accompanied by inflammatory reactions that lead to a violation of the indicators of a specific link of the immune response (сytotoxic activity of lymphocytes, сytotoxic activity of macrophages, antibody-dependent cytotoxicity of lymphocytes, antibody-dependent cytotoxicity of macrophages, сytotoxic activity of lymphocytes+macrophages, antibody-dependent cytotoxicity of lymphocytes+macrophages, lysis ability of serum) and the accumulation of factors that at different stages of the inflammatory process block reactions mediated by lymphocytes or macrophages against the background of their preserved ability to manifest cytotoxic activity, in the blood serum. The therapeutic effect of MCI-4 pessaries in the therapeutic mode of administration in conditions of formed vaginitis of mixed etiology (S. aureus and C. albicans), which was confirmed by normalization of the state of the vaginal epithelium of animals and indicators of the immune system after a single daily administration of MCI 4 for 5 days. Therapy with MCI-4 pessaries leads to activation of the body's immunological reactivity. It was found that the components of MCI-4 showed distinct inhibitory properties against biofilms of monocultures of aerobic bacteria and bacterial-fungal associations.