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Modern technologies for the manufacture of phage preparations provide a high degree of purification from the products of bacterial activity, endotoxins and exotoxins, products of phagolysis of bacterial cells. However, bacteriophage preparations should be tested for safety and the absence of bacterial or other toxic contaminants. Confirmation of the safety of bacteriophage drugs is the study of their toxicity administered into the stomach once or over a period of time. The aim of the study was to determine the acute and chronic toxicity of the drug based on bacteriophages "Fagomast" for the treatment of mastitis in cows. Experimental studies to determine the toxicity of the drug "Fagomast" were performed on white mice by oral administration according to current methods. Clinical trials have been conducted in accordance with the ethical principles of the European Convention for the Protection of Vertebrate Animals Used for Research and Other Scientific Purposes. The results were calculated by the Kerber method. The experiment to determine acute toxicity lasted for 14 days. During the experiment, the behavior of animals was observed, and the number of deaths in each group was recorded. In vivo toxicity assessment, namely the determination of acute toxicity with a single administration and repeated use of the drug aims to determine the potential development of bacteriophage-induced toxic effects on living organisms. Studies have shown that the acute toxicity of the drug "Fagomast" corresponds to the LD50 - 5000 mg / kg live weight of animals. The drug does not have cumulative properties. The concentration of the drug does not cause irritation. It has no sensitizing properties and is non-toxic when ingested orally. Blood morphological parameters did not change significantly. According to the established signs, the working solutions of the drug "Fagomast" are classified as class IV (low-toxic) safety.

The reproductive function of cows is ensured by a homeostasis system. The aim of this study to investigate scientific data and analyze modern practical approaches related to metabolic disorders. Also investigating immune response. The object of the research was the cows (Bos taurus taurus) of Ukrainian Black-and-White dairy breed. Using the method in groups and periods. The control group of animals The control group of animals (C1, n=137) – cows with a physiological of pregnancy (248-255 days). Re-examination of control animals (C2, n=137) was carried out during the postpartum period. The first experimental group (E1, n = 32) consisted of animals diagnosed with preeclampsia. Cows with a subclinical course of ketosis constituted the second group (E2, n = 52). The development of preeclampsia of cows was accompanied by an increase in the content of medium-sized peptides from 0.2 ± 0.01 to 0.3 ± 0.03 Mol.Wt. (P < 0.01), and an increase in the level of average molecular circulating immune complexes. It is proved that an imbalance in the diet and a deficiency of metabolic energy during the dry period and for 6-8 weeks after birth negatively affects the health of animals, is the cause of metabolic disorders and the manifestation of reproductive pathologies.

Therapeutic effect in case of phagotherapy is determined by the degree of lytic activity of bacteriophages in relation to contagions. Various factors influence the lytic activity of phages including temperature, pH, shelf-life, etc. Temperature plays a considerable role in attachment, penetration, reproduction and duration of latent period. The purpose of this research was to learn the influence of different temperature on lytic activity of bacteriophage Phage SAvB14 which is active in relation to Staphylococcus aureus variant bovis. For the increase of bacteriophage titre Phage SAvB14 the strain of gold Staphylococcus aureus var. bovis 1491f (Certificate for the strain - #736, from 05.03.2019) was used which was abstracted from the sample of the secretion of mammary gland of the patient with subclinical form of mastitis. For determination of temperature influence (0, 4, 8 and 45, 55, 65 °C) aliquots were sown by a double agar in definite intervals by the generally accepted methods. The cups were incubated at temperature 37 °C during 18-24 hours. Research was repeated three times. According to the results of research it was determined that warming up of test tubes with bacteriophages at temperature 45 oС reduced the activity of phages in 30 minutes of influence in 1,7 times. Temperature 55 and 65 oС had more harmful effect, during the influence for the first 30 minutes the amount of active phages diminished in 2,5 and 5,3 times, and for 60 minutes destroyed the bacteriophage Phage SAvB14 by 89,9 and 93,3% respectively. The obtained results testify the thermolability of Phage SAvB14 which is an important factor in making phage preparation. The most optimum terms for storage of Phage SAvB14 are temperature regime within the limits of 4 and 8 °C. In case of such temperature lytic activity diminished only in 1,5 – 1,7 times, while in case of 0 °C in 2,4 times compared to the initial amount of bacteriophages.