RU2401111C1 - Preparation for treating salmonellosis in young live-stock animals - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: preparation for treating salmonellosis in young live-stock animals contains, wt %: colistin sulphate 4.0-6.0; tylosin base 4.0-6.0; sodium pyrosulphite 0.32; benzyl alcohol 4.0; water for injections 15.0; 1,2-propyleny glycol - to 100.0.

EFFECT: higher effectiveness of treating salmonellosis in young live-stock animals.

14 tbl, 5 ex

Description

The invention relates to the field of veterinary medicine.

The damage caused by salmonellosis is the sum of the losses caused by the death of young animals, the lag in growth and development of sick animals, as well as the costs associated with the organization of preventive and therapeutic measures. Mortality in salmonellosis of young animals reaches 40-50%. Salmonellosis is distinguished by many forms of the course, and besides carriage in animals, diphtheria colitis (diarrhea of various degrees of severity), arthritis and pneumonia (in the chronic course), sepsis, abortion, meningoencephalitis, foodborne toxicoinfection, and less commonly other pathologies are noted. Quite often, salmonellosis occurs in conjunction with other bacterial and invasive (colibacteriosis, pseudomonosis, dysentery, pasteurellosis, diplococcosis, clostridiosis, bordetellosis, balantidiosis, ascariasis, trichocephalosis, cryptosporidiosis) and some other diseases [Efanova L. Diagnosis of the most common infectious diseases of calves and piglets. - Voronezh: VGAU, 1995. - 128 p .; Kareva E.P., Soldatenko N.A., Zimina V.N. Features of the epizootology of pig salmonellosis // Ecological aspects of the epizootology and pathology of animals, Voronezh, 1999. - P.472-474].

The success of the fight against infectious diseases, including salmonellosis, largely depends on the right treatment regimen. The widespread introduction of antibacterial drugs in the practice of livestock farms in the initial period of their use created the illusion of solving the problem of bacterial infections. However, the effectiveness of many antibiotics, as well as other antibacterial drugs, is sharply reduced due to the wide distribution of antibiotic-resistant strains of microorganisms.

The problem of resistance of microorganisms to various antibacterial drugs appeared shortly after the start of their widespread use in clinical practice. In this connection, the urgency of the problem of treatment of infectious diseases caused by multiresistant strains of bacteria is not in doubt. The possible ways to solve it may be either the synthesis of new antibacterial agents, or the optimization of the use of available drugs [Efanova LI Some environmental aspects of the use of antibiotics in veterinary practice // Ecological problems of pathology, pharmacology and animal therapy: abstract. doc. - Voronezh, 1997 .-- S.307-308. Shakhov A.G. Etiology and prevention of gastrointestinal and respiratory diseases of calves and piglets / A.G. Shakhov // Veterinary consultant. - 2003. - No. 1. - S.4-5].

Often, a complex of antibacterial substances has a synergistic effect, which allows to reduce the dose of the drug or to develop a more convenient treatment regimen, thereby reducing the risk of side effects.

A known drug for the treatment of gastrointestinal diseases of young animals, the following composition, wt.%: Polyvinyl ethinyltrimethylpiperidol hydrosulfate 0.8-1.2; iodine 0.1-0.3; potassium iodide 0.3-1.0; polymyxin 0.02-0.04; distilled water - the rest. To piglets, the drug is administered orally at a dose of 1 ml per 1 kg of body weight twice a day for 3-4 days [RU 2054941 C1, 02.27.1994].

Known drug for the treatment of gastrointestinal diseases of young animals - the drug "Rifapol", which contains, wt.%: Polymyxin 0.6-0.9, rafampicin 10.0-15.0. The drug is administered orally twice a day for 2-4 days at a dose of 1 ml / kg of animal weight [Veterinary preparations in Russia: Handbook in 2 volumes. T.1. / I.F. Klenova, K.L. Maltsev, N.A. Yaremenko, I.A. Arkhipov.- M .: Selkhozizdat, 2004. - P.213].

Known tool for the treatment of gastrointestinal diseases of farm animals "Enrokoli". The producer of Enrokoli is the Spanish company JV Veterinary SA. The preparation contains: enrofloxacin - 10.0% and various colistin contents - from 50.0 million IE and above [Veterinary preparations in Russia: A Handbook in 2 volumes. T.1 / I.F. Klenova, K.L. Maltsev, N.A. Yaremenko, I.A. Arkhipov.- M .: Selkhozizdat, 2004. - P.209].

The well-known drug "Tilosin 50 solution for injection", which is a clear yellow solution, 1 ml of which contains 50 mg of tylosin in the form of a base [Veterinary preparations in Russia: Handbook in 2 volumes. T.1. / I.F.Klenova, K.L. Maltsev, N.A. Yaremenko, I.A. Arkhipov. - M .: Selkhozizdat, 2004. - P.183].

The well-known drug is not always sufficiently effective and leads to the complete recovery of all sick animals, due to the fact that it is active mainly against gram-positive and some gram-negative microorganisms.

The prototype of the invention is a powder for oral use "Rovastin" for the treatment and prevention of infectious diseases of farm animals and birds, the causative agents of which are sensitive to colistin and spiramycin, which is a white, loose, bitter taste powder, readily soluble in water with a content of 100 g: colistin 50 million units, spiramycin 65 million units and glucose up to 100 g. The drug is prescribed orally, individually or in a group method, with food or drinking water. The drug is prescribed to the bird at the rate of 0.5-1 g per 1 liter of water daily, for 2-5 days. Animals are prescribed in a dose of 1-2 g per 10 kg of body weight, once a day, daily for 2-5 days [Veterinary preparations in Russia: Handbook in 2 volumes. T. 1 / I.F.Klenova, K.L. Maltsev, N.A. Yaremenko, I.A. Arkhipov. - M .: Selkhozizdat, 2004. - P.215].

However, the use of these drugs does not always lead to positive results in the treatment of salmonellosis. With oral administration of drugs in the treatment of salmonellosis, it is preferable to use active ingredients with good bioavailability. Colistin is practically not absorbed from the gastrointestinal tract. The concentration in the blood serum is 2-3% of the administered dose. On the other hand, the pharmacodynamic spectrum of changes, of course, is more pronounced with parenteral routes of administration, and these drugs are given to sick animals with food or drink.

The technical result is an increase in the effectiveness of the treatment of salmonellosis in young farm animals.

The technical result is achieved using a preparation consisting of the following components wt.%:

Colistin sulfate - 4.0-6.0;

Tylosin base - 4.0-6.0;

Sodium pyrosulfite - 0.32;

Benzyl alcohol - 4.0;

Water for injection - 15.0;

1,2-Propylene glycol - up to 100.0%.

Optimum is the following ratio of components, wt.%:

Colistin sulfate - 5.0;

Tylosin base - 5.0;

Sodium pyrosulfite - 0.32;

Benzyl alcohol - 4.0;

Water for injection - 15.0;

1,2-Propylene glycol - up to 100.0%.

The main purpose of the combined use of colistin and tylosin is to expand the spectrum of antibacterial action, fill in the gaps in the spectrum of each of the components of the combination and prevent the formation of resistance of microorganisms.

The combined use of tylosin and colistin provides an increase in the effectiveness of the treatment of salmonellosis, a quick recovery of sick animals, a decrease in the consumption of active substances and their side effects on the body.

Colistin sulfate (polymyxin E) is a polymyxin produced by Bacillus polymyxa. Polymyxin E is active against salmonella, E. coli, pseudomonas, Shigella, hemophilus, aerobacteria, pasteurell, bordetell, Klebsiella [British Pharmacopoiea, 2007, v. I & II, P.448; David Bernala, J. M. Llop, E. Fort, M.B. Badia, R. Jadar. Use colistin in the Treatment of Multie-Drug-Resistant Gram-Negative Infections / Am.J. health-Syst Pharm, 2005; 62 (1): 39-47].

The mechanism of action is the bactericidal action on the cytoplasmic membrane of a bacterial cell, interacting with phospholipids. They bind to anionic sections of the membrane and resemble cationic detergents in the nature of their action. Damage to the membrane structure leads to a change in its permeability for both intracellular and extracellular components [Fernandes-Viladrich P., Corbella X., Corral L. et al. Successful treatment of ventriculitis due to carbapenem-resistant Acinetobacter baumannii with intraventricular colistin sulfomethat sodium. Clinical Infect. Dis., 1999; 28: 916-7].

Tylosin base is an antibiotic from the macrolide group, the producer of which is Streptomyces Fradiae. The basis of its chemical structure is a macrocyclic lactone ring with one or more carbohydrate residues [Dorozhkin VI, Biryukova NP, Antipov VA Testing of antimicrobial agents based on tylosin // Sat. scientific tr VNIVIPFiT “Use of new diagnostic methods and pharmacological agents in the treatment and prevention of non-communicable animal diseases”. Voronezh, 1993. - P.26-30; Klyuchnikov S.O., Boldyrev V.B. Possibilities of using macrolides in children in modern conditions / Bulletin of Pediatric Pharmacology and Nutrition / Volume 4, No. 3, 2007. - P.16-23; British Pharmacopoiea, 2007 (Vet.), P. 58].

One of the common properties of macrolides is the bacteriostatic effect, which is due to a violation of protein synthesis in the microbial cell by irreversible binding to the 5OS subunit of the ribosome [Klyuchnikov SO, Boldyrev VB Possibilities of using macrolides in children in modern conditions / Bulletin of Pediatric Pharmacology and Nutrition / Volume 4, No. 3, 2007. - P.16-23].

Macrolides are characterized by a post-antibiotic effect, manifested in the absence of the effect of the resumption of bacterial growth, despite the removal of the antibiotic from the body [Klyuchnikov S.O., Boldyrev VB Possibilities of using macrolides in children in modern conditions / Bulletin of Pediatric Pharmacology and Nutritionology / Volume 4, No. 3, 2007. - P.16-23], anti-inflammatory and immunomodulatory effects. They increase the activity of T-killers, accumulate in neutrophils and macrophages, enhance their phagocytic activity and migration to the focus of inflammation.

Tylosin base inhibits the reproduction and development of gram-positive bacteria (streptococci, staphylococci, pneumococci, corynebacteria, clostridia, erizipelotriks), gram-negative (pasteurell, hemophilus, brucella), mycoplasmas, protozoa vibrios, leptospira, neisseria, spreys, .I., Biryukova N.P., Antipov V.A. Testing of antimicrobial agents based on tylosin // Sat. scientific tr VNIVIPFiT “Use of new diagnostic methods and pharmacological agents in the treatment and prevention of non-communicable animal diseases”. Voronezh, 1993. - P.26-30; Sazonova E.M., Vyduykina A.P., Krutlyak E.B. and others. Obtaining a working standard sample of tylosin // Sat-to scientific. tr VGNKI, M., 1994, T. 56. - S.104-109].

It is this combination of active ingredients that expands the spectrum of the antibacterial action of the drug, prevents the development of resistance of microorganisms.

Sodium pyrosulfite is a white crystalline powder with a strong odor of sulfur dioxide, readily soluble in water. It is used as a stabilizer [British Pharmacopoiea, 2007, v. I & II, p. 1520].

Benzyl alcohol - the chemical formula C ₆ H ₅ CH ₂ OH. It is a colorless liquid with a slight aromatic odor, soluble in all common organic solvents, with the exception of petroleum ether. 4 parts of benzyl alcohol are dissolved in 100 parts of water. It is used as a solvent, odor fixer in perfumes, preservative [Polydec-Fabini R., Beirich T. Organic analysis: Trans. with him. - L .: Chemistry, 1981. - P.61; British Pharmacopoiea, 2007, vI & II, p. 171].

Water for injection is obtained by distillation or osmosis. The water obtained is pyrogen-free, does not contain antimicrobial substances and other additives, the maximum permissible level of bacterial endotoxins is 0.25 U / ml [Pharmacopoeia article FS 42-2620-97, Ministry of Health and Medical Industry of the Russian Federation, Pharmacopoeia State Committee, approved 11.03.97 . - 4 p.].

1,2-Propylene glycol is the chemical formula of CH ₃ CHONSH ₂ OH. It is a transparent, colorless, odorless, viscous with a sweet taste taste, soluble in water, alcohol and chloroform [British Pharmacopoiea, 2007, vI & II, P.1392; Polydec-Fabini R., Beirich T. Organic analysis: Per. with him. - L .: Chemistry, 1981. - S.68-69].

The drug for the treatment of salmonellosis in young farm animals is heated to 37-38 ° C before use. The drug is administered intramuscularly daily once a day at a dose of 0.05 ml / kg body weight (calves) and 0.075 ml / kg (piglets) for 3-5 days, for severe illness - for 5-7 days.

Calves are not recommended to inject more than 5 ml in one place, and piglets - more than 2.5 ml of the drug. With the introduction of large volumes, the dose is divided and administered in different places. With repeated injections, it is recommended to change the injection site.

In recommended doses, the drug does not cause side effects and complications. After injection of the drug in animals, a short-term pain reaction and anxiety may occur.

The drug is contraindicated in animals with hypersensitivity to colistin and tylosin. Slaughter of animals for meat is allowed no earlier than 10 days after the last injection of the drug. The meat of animals forced to be killed before the expiration of the specified period can be used for feeding carnivores or for the production of meat and bone meal.

A preparation is being prepared for the treatment of salmonellosis in young farm animals as follows. Propylene glycol is heated in a reactor with a contact thermometer and loop heating and cooling to a temperature of 50 ± 5 ° C. Then, tylosin base, colistin sulfate, sodium pyrosulfite, benzyl alcohol, water for injection are introduced into the reactor sequentially, with an interval of 10 minutes. Mixing is carried out at a temperature of 40 ± 5 ° C until the components are completely dissolved. Packing of the drug is carried out in a box, pre-treated for 1 hour with a bactericidal lamp. The ampoules are sealed, the bottles are closed with a rubber stopper and sealed with aluminum caps. In the process of packing, an intermediate check is carried out for the presence of mechanical inclusions (visually with the naked eye on black and white backgrounds) and for the volume of filling of ampoules and vials (using a calibrated syringe or cylinder). The control of the filling volume is carried out with an interval: when filling 100-50 ml - every 200 packing units, when filling 20-10 ml - every 300 packing units, when filling in ampoules - every 500 packing units. The filling volume of the vials must be at least nominal.

The essence of the technical solution is illustrated by examples.

Example 1. Determination of the optimal ratio of components in the preparation for the treatment of salmonellosis in young farm animals, the study of its antimicrobial properties.

The antimicrobial properties of the drug were studied. The optimal quantitative content of tylosin and colistin was revealed in experiments in vitro and in vivo. In model experiments, it was found that the drug has a wide spectrum of antimicrobial activity in relation to the tested cultures of microorganisms.

In vitro experiments

The antimicrobial activity and the ratio of colistin and tylosin in the preparation for the treatment of salmonellosis in young farm animals were studied in vitro by the method of serial dilutions. As test cultures, reference and field (pathogenic) strains of microorganisms, the causative agents of gastrointestinal diseases of piglets and calves, typified by morphological, tinctorial, cultural, biochemical and serological properties were used. The ratio of colistin and tylosin in the drug for the treatment of salmonellosis in young farm animals in the following combinations.

Combination 1. The composition of the drug for the treatment of salmonellosis in young farm animals; components, wt.%:

Colistin sulfate - 5.0;

Tylosin base - 5.0;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

Combination 2. The composition of the drug for the treatment of salmonellosis in young farm animals; components, wt.%:

Colistin sulfate - 4.5;

Tylosin base - 5.5;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

Combination 3. The composition of the drug for the treatment of salmonellosis in young farm animals; components, wt.%:

Colistin sulfate - 5.5;

Tylosin base - 4.5;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

Combination 4. The composition of the drug for the treatment of salmonellosis in young farm animals; components, wt.%:

Colistin sulfate - 4.0;

Tylosin base - 6.0;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

Combination 5. The composition of the drug for the treatment of salmonellosis in young farm animals; components, wt.%:

Colistin sulfate - 6.0;

Tylosin base - 4.0;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

The antimicrobial activity of various combinations of the composition of the drug was compared with the antimicrobial activity of colistin and tylosin.

The minimum bacteriostatic concentration (MBsK) of the studied drugs was determined by the method of serial dilutions in meat-peptone broth (BCH); minimum bactericidal concentration - by seeding from tubes with a transparent medium on solid nutrient media (MPA) that do not contain the drug. As a liquid nutrient medium, meat-peptone broth was used.

The main solution of the drug (1000 μg / ml) was prepared taking into account the density of the drug. A working solution was prepared from the main solution of the preparation. Then, 4.5 ml of meat-peptone broth were poured into 16 sterile tubes. 4.5 ml of the preparation was added to 1 tube, mixed, after which 4.5 ml of the resulting solution was transferred to the next tube, thus continuing dilution to 15 tubes. As a control of the growth of the culture used 16 test tube containing no drug.

The content of microbial cells in 1 ml of medium was 500 thousand.

Crops were incubated at 37 ° C for 18-20 hours. After the incubation period, the result was taken into account.

The results of a study of the antimicrobial activity of colistin, tylosin and various combinations are presented in table 1.

As can be seen from the data presented, the drug has a high antibacterial effect against the main pathogens that cause salmonellosis in young farm animals. Depending on the strain, the minimum bacteriostatic concentration (MBsK) for salmonella was 0.78-3.12 μg / ml for colistin and 6.25 μg / ml for tylosin.

Table 1 Antimicrobial activity (MBSK) of colistin, tylosin and various drug compositions, μg / ml Composition TO T By Σ DW In terms of TO T S. dublin 593/75 K1 0.78 6.25 0.78 0.390 0.390 K2 0.78 0.351 0.429 K3 0.78 0.429 0.351 K4 0.78 0.312 0.468 K5 0.78 0.468 0.312 S. choolerae suis K1 3.12 6.25 0.39 0.195 0.195 K2 1,56 0.702 0.858 K3 0.39 0.215 0.175 K4 1,56 0.624 0.936 K5 1,56 0.936 0.624 Designations: K - colistin; T - tylosin; K1 - composition 1; K2 - composition 2; K3 - composition 3; K4 - composition 4; K5 - composition 5

With respect to S. dublin, the antimicrobial activity of all the studied compositions in absolute weight did not change compared to colistin, and increased by 8 times compared to tylosin. At the same time, the combined use of colistin and tylosin allowed to reduce the MBsK of compositions 1-5 for this culture for colistin to 0.390, 0.351, 0.429, 0.312 and 0.468 μg / ml (1.7-2.5), and for tylosin MBsK decreased by 16.0, 14.7, 17.8, 13.4 and 20.0 times, respectively.

In relation to S. cholerae suis, the antimicrobial activity of compositions 1 and 3 in absolute weight increased by 8 times compared with colistin, and by 16 times compared to tylosin, by compositions 2, 4 and 5, by 2 and 4 times, respectively. At the same time, the combined use of colistin and tylosin allowed to reduce MBSK for this culture to a large extent for both colistin and tylosin in compositions 1 and 3. For colistin, to 0.195 and 0.215 μg / ml, and for tylosin, to 0.195 and 0.175 μg / ml, which is 16.0-14.5 times higher than colistin and 32.0-35.7 times higher for tylosin. For composition 2, MBSK decreased for colistin to 0.702 μg / ml (4.4 times) and for tylosin to 0.858 μg / ml (7.3 times); in composition 4, for colistin up to 0.624 μg / ml (5 times), and for tylosin - up to 0.936 μg / ml (6.7 times); in composition 5, for colistin - up to 0.936 μg / ml (3.3 times), for tylosin - up to 0.624 μg / ml (10 times).

Thus, the study of the antimicrobial activity of various compositions of the drug and individual components showed the presence of mutually reinforcing (synergistic) action in relation to the studied pathogenic cultures. In vitro experiments have established that combination 1 can be considered the most active composition.

1.2. The study of the optimal ratio of colistin and tylosin in experiments in vivo

Based on the results obtained in experiments in vitro in experiments in vivo tested 3 compositions. Their effectiveness was determined in model experiments during experimental infection of white mice with Salmonella cholerae suis (2.0 million m.k. / mouse), Salmonella dublin (2.5 million m.k. / mouse).

The experiments were carried out on sexually mature conventional non-linear heterosexual white mice with a body weight of 20-22 g of vivarium dilution of the All-Russian NIVI pathology, pharmacology and therapy. Animals were kept in vivarium conditions at 20-22 ° C and humidity 40-60%. Keeping animals and providing food was in compliance with the regulatory requirements of the International Convention.

Groups of animals were formed according to the principle of analogues of 8 animals each, taking into account body weight, development and clinical condition. Animals of the control groups were not treated. The experimental animals were monitored for 15 days, taking into account the incidence, death, timing of recovery. The specificity of death was determined by the bacteriological method of isolating the initial cultures of microorganisms.

Infection of animals was carried out intraperitoneally by flushing daily agar cultures of pathogens. Cultivation was done on sterile saline. The concentration of microbial cells was determined according to the turbidity standard. In preliminary experiments, DLM of the experimental cultures was determined, which amounted to 2 million m.s. for Salmonella cholerae suis, 2.5 million m.s. for Salmonella dublin

For prophylactic purposes, the drug was administered once at the same time as infection at a dose of 0.075 ml / kg. Treatment of mice was started 6 hours after infection. The drug was administered once a day intramuscularly in the same dose.

The preventive efficacy of the drug was judged by the number of surviving mice after the end of the experiment and the number of mouse days for each group 15 days after infection.

During experimental infection of Salmonella cholerae suis mice, a single injection of composition 1 at a dose of 0.075 ml / kg ensured the safety of animals within 62.5% at 100.0% death of animals in the control group (table 2). The prophylactic efficacy of this composition for infection of white Salmonella dublin mice was 12.5% lower.

table 2 Prophylactic efficacy of various compositions of the drug in experimental infection of white mice Group The number of mice in the group goal. Fallen goal Survived Mouse-days of life Goal % Salmonella cholerae suis (2 million sq.m.) The control 8 8 0 0 26 Combination 1 8 3 5 62.5 84 Combination 2 8 5 3 37.5 68 Combination 3 8 four four 50,0 80 Salmonella dublin (2.5 million sq.m.) The control 8 8 0 0 25 Combination 1 8 four four 50,0 75 Combination 2 8 6 2 25.0 54 Combination 3 8 5 3 37.5 69

During experimental infection of Salmonella cholerae suis mice, a single injection of composition 3 at a dose of 0.075 ml / kg ensured the safety of animals within 50.0% with 100.0% death of animals in the control group. The prophylactic efficacy of this composition for infection of white Salmonella dublin mice was 12.5% lower.

When using composition 2, the prophylactic effectiveness was lower by 25.0% than when using composition 1 and by 12.5% than when using composition 3.

An increase in the total life expectancy of white mice was also noted, depending on the pathogen microorganism and the composition used. In infections caused by Salmonella, the total life expectancy of white mice was 80-84 days (Salmonella cholerae suis) and 69-74 days (Salmonella dublin) when using combinations 1 and 3. The total life expectancy of mice when applying composition 2 was lower for all species infections and averaged 61 days. Thus, and for this indicator, the highest results were noted in compositions 1 and 3.

The therapeutic efficacy of the drug was judged by the number of surviving mice after treatment and the number of mouse days for each group 15 days after infection.

During experimental infection of Salmonella cholerae suis mice, treatment of animals with compositions 1 and 3 at a dose of 0.075 ml / kg ensured the safety of animals within 75.0% with 100.0% death of animals in the control group (table 3).

Table 3 The therapeutic efficacy of various compositions of the drug in experimental infection of white mice Group The number of mice in the group, goals Fallen, goals Survived Mouse-days of life goals % Salmonella cholerae suis (2 million sq.m.) The control 8 8 0 0 26 Combination 1 8 2 6 75.0 99 Combination 2 8 3 5 62.5 86 Combination 3 8 2 6 75.0 98 Salmonella dublin (2.5 million sq.m.) The control 8 8 0 0 25 Combination 1 8 3 5 62.5 95 Combination 2 8 four four 50,0 76 Combination 3 8 3 5 62.5 86

The effectiveness of this composition in the treatment of white mice infected with Salmonella dublin was lower by 12.5% compared with that in salmonella infection caused by Salmonella cholerae suis.

When using composition 2 for all types of infections, the treatment efficiency was lower by 12.5% than when using compositions 1 and 3.

An increase in the total life expectancy of white mice was also noted, depending on the pathogen microorganism and the composition used. In infections caused by Salmonella, the total life expectancy of white mice was 86 - 99 days. Thus, and for this indicator, the highest results were noted in compositions 1 and 3.

Summing up the data of in vitro and in vivo experiments, it was found that composition 1 turned out to be the most effective.

In this regard, the antimicrobial activity of the drug was studied in more detail. The results of the experiment are presented in table 4.

According to the data presented in table 4, the drug for the treatment of salmonellosis in young farm animals has pronounced antimicrobial properties. The minimum inhibitory effect of the drug for the treatment of salmonella in young farm animals in relation to museum strains of salmonella was established at a concentration of 0.39-1.56 μg / ml, and in the field 1.56-3.12 μg / ml. The bactericidal effect of the drug in relation to the studied cultures exceeded the bacteriostatic 2 times.

Table 4 Antimicrobial activity of the drug for the treatment of salmonellosis in young farm animals Microorganism culture A drug MBcK, mcg / ml MBcK, mcg / ml S. choolerae suis 0.39 0.78 S. choolerae suis (n) 1,56 3.12 S.dublin 593/75 0.78 1,56 S.dublin 1,56 3.12 S.thyphimurium 3.12 6.25 S.thyphimurium 383/144 1,56 3.12

Studies have shown that the drug for the treatment of salmonellosis in young farm animals has a wide spectrum of antimicrobial activity against gram-positive and gram-negative microorganisms.

As a result of studying the antimicrobial effect of tylosin in combination with colistin in experiments in vivo and in vitro, it was found that these drugs have a mutually reinforcing effect against the studied strains of microorganisms. The use of tylosin and colistin complexes ensured the safety of animals during treatment from 62.5 to 75.0%, and during prevention from 50.0-62.5%, depending on the pathogen microorganism.

Example 2. Determination of the optimal therapeutic composition of the drug for the treatment of salmonellosis in young farm animals.

The development of the optimal therapeutic composition of the drug was carried out in experiments on 4 groups of calves with salmonellosis. Animals in groups were selected on the basis of analogues.

The diagnosis of salmonellosis was established comprehensively on the basis of data from a clinical examination of animals, autopsy, laboratory tests taking into account the epizootic situation on the farm.

The calves of the control group were treated with 5% enroxil produced by KRKA (Slovenia) [Veterinary preparations in Russia: A Handbook in 2 volumes. T. 1 / I.F.Klenova, K.L. Maltsev, N.A. Yaremenko, I.A. Arkhipov. - M .: Selkhozizdat, 2004. - P.226-227], which was administered subcutaneously at a dose of 1 ml / 20 kg of body weight 1 time per day for 5 days.

The animals of the experimental groups for treatment used the following composition of the drug.

Combination 1. The composition of the drug for the treatment of salmonellosis in young farm animals; components, wt.%:

Colistin sulfate - 5.0;

Tylosin base - 5.0;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

Combination 4. The composition of the drug for the treatment of salmonellosis in young farm animals; components, wt.%:

Colistin sulfate - 4.0;

Tylosin base - 6.0;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

Combination 5. The composition of the drug for the treatment of salmonellosis in young farm animals; components, wt.%:

Colistin sulfate - 6.0;

Tylosin base - 4.0;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

The drug for the treatment of salmonellosis in young farm animals was used intramuscularly at a dose of 0.05 ml / kg body weight five times with an interval of 24 hours.

The therapeutic efficacy of various compositions of the drug was evaluated by the number of recovered calves within 10 days from the start of treatment (table 5).

Table 5 Testing the optimal therapeutic composition of the drug for the treatment of salmonellosis in young farm animals Indicators Group of animals The control K1 K4 K5 Number of animals, goals 25 25 25 25 Duration of treatment, days 5.7 ± 0.5 3.9 ± 0.4 4.1 ± 0.3 5.1 ± 0.4 Recover, Goals twenty 23 23 22 % 80.0 92.0 92.0 88.0 Fallen, goals one - - one % 4.0 - - 4.0 Therapeutic efficacy,% 80.0 92.0 92.0 88.0 Note: K1 - composition 1; K4 - composition 4; K5 - composition 5.

In the control group, the disappearance of clinical signs of the disease occurred on average on the 6th day of treatment and was observed in 20 calves, which amounted to 80.0%.

In the first experimental group, where composition 1 was used at a dose of 0.05 ml / kg once a day, the disappearance of clinical signs of the disease occurred on the 3-4th day of treatment and was observed in 23 calves, which amounted to 92.0%.

In the second experimental group, where composition 4 was used at a dose of 0.05 ml / kg once a day, the disappearance of clinical signs of the disease occurred on average on the 4th day of treatment and was observed in 23 calves, which amounted to 92.0%.

In the third experimental group, where composition 5 was used at a dose of 0.05 ml / kg once a day, the disappearance of clinical signs of the disease occurred on the 4-5th day of treatment and was observed in 22 animals, which amounted to 88.0%.

As can be seen from the presented data (table 5), compositions 1 and 4 at a dose of 0.05 ml / kg have a significant therapeutic effect, the number of recovered animals was 92.0%, which is 12.0% higher than the control.

When using composition 5, the therapeutic effect increases by 8.0% compared with the control group, and lower by 4.0% compared to compositions 1 and 4.

At the same time, the disappearance of clinical signs of the disease occurred earlier in the group of animals that were treated with composition 1, which indicates the economic feasibility of using the drug at a dose of 0.05 ml / kg body weight with an interval of 24 hours.

Thus, it was found that the optimal therapeutic composition of the drug for the treatment of salmonellosis in young farm animals is composition No. 1.

Example 3. The study of the effectiveness of the treatment of salmonellosis in calves.

The study was carried out in three experiments on calves 1-3 months of age, patients with salmonellosis. According to the principle of paired analogues, taking into account the general condition and severity of the disease, sick calves were divided into two groups (control, experience). The diagnosis of salmonellosis was established comprehensively on the basis of data from a clinical examination of animals, bacteriological studies (cultures of Salmonella typhimurium and Salmonella dublin were isolated and studied during bacteriological examination of feces), postmortem examination, taking into account the epizootic situation on the farm.

The animals were monitored daily for 10-15 days, taking into account the general condition, mortality, growth rate, and timing of recovery.

In experiments No. 1 and 2, the calves of the control group were treated with 5% enroxil produced by KRKA (Slovenia) [Veterinary preparations in Russia: Handbook in 2 volumes. T. 1 / I.F.Klenova, K.L. Maltsev, N.A. Yaremenko, I.A. Arkhipov. - M .: Selkhozizdat, 2004. - P.226-227], which was administered subcutaneously at a dose of 1 ml / 20 kg of body weight 1 time per day for 3-5 days. In the third experiment, the calves of the control group were treated with a solution of gentamicin sulfate 4%, which was administered intramuscularly at a dose of 3 mg / kg live weight twice a day for 3-5 days.

For the animals of the experimental group, a preparation was used to treat salmonellosis in young farm animals in the following ratio of components, wt.%:

Colistin sulfate - 5.0;

Tylosin base - 5.0;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

The drug for the treatment of salmonellosis in young farm animals was used intramuscularly at a dose of 0.05 ml / kg body weight three times with an interval of 24 hours. In severe cases of the disease, four to five injections were performed at intervals of 24 hours.

The first experience in studying the effectiveness of the treatment of calf colibacillosis was carried out at the milk production complex of the joint venture “Saburovo” of the agricultural complex “Oryol Niva” in the Oryol region of the Oryol region in November 2007 - January 2008.

In patients, depression, tachycardia (107 ± 3.5 beats per minute), decreased appetite and average daily weight gain (from 880 to 562 g) were observed, body temperature at the onset of the disease was 39.9 ± 0.4 ° C. Diarrhea was observed in 55% of the animals, with feces with a high content of mucus, and some, in addition, noted the presence of blood. 73% of patients had shortness of breath, serous or serous-purulent discharge from the nose. With postmortem autopsy, 96.5% of patients had hemorrhagic enteritis, 7% had fibrinous colitis and 3% had ulcerative abomazitis. The mesenteric, bronchial and mediastinal lymph nodes are enlarged, juicy in the section, the structure is not changed. The liver is flabby, clay in color with multiple foci of gray. The lungs are cherry red with areas of compaction, and some have abscesses in the thickness of the lung tissue.

The results of the therapeutic efficacy of the drug for the treatment of salmonellosis in young farm animals are presented in table 6.

Table 6 Therapeutic efficacy of the drug for the treatment of salmonellosis in young farm animals in the joint venture "Saburovo" JSC agro-industrial complex "Oryol Niva", Oryol region, Oryol region Indicators Group of animals control experienced Number of animals, goals 60 65 Recover, Goals 47 61 % 78.3 93.8 Fallen, goals four 0 % 6.7 0 Transition to a chronic form, change of treatment, goals 9 four % 15.0 6.2 Duration of recovery, days 5.5 ± 1.0 3.7 ± 0.5

From the data of table 6 it is seen that the therapeutic effect in the control group was 78.3%, mortality 6.7%. Among the calves from the experimental group, the treatment efficiency reached 93.8%, and no deaths were observed.

The second experience in studying the effectiveness of the treatment of calf salmonellosis was carried out in the agricultural school Zarya in the Pavlovsky district of the Voronezh region in January - March 2008.

The results of the therapeutic efficacy of the drug for the treatment of salmonellosis in young farm animals are presented in table 7.

Table 7 Therapeutic efficacy of the drug for the treatment of salmonellosis in young farm animals in the agricultural school "Zarya" Pavlovsky district of Voronezh region Indicators Group of animals The control Experience Number of animals, goals 59 64 Recover, Goals 48 56 % 81.4 87.5 Fallen, goals 2 0 % 3.4 0 Stayed sick goals 9 8 % 15,2 12.5 Duration of recovery, days 5.2 ± 0.5 4,5 ± 0,2 Therapeutic efficacy,% 81.4 87.5

From the data of table 7 it is seen that the therapeutic effect in the control group was 81.4%, mortality 3.4%. Among the calves from the experimental group, the treatment efficiency reached 87.5%, and no deaths were observed. Compared with the calves of the control group, when using the drug for the treatment of salmonellosis in young farm animals, the calf recovery period decreased by 13.5%.

The third experience in studying the effectiveness of parenteral use of the drug for the treatment of salmonellosis in calves was carried out in LLC “A / f Nastyusha-Gryazi” in the Gryazinsky district of the Lipetsk region in February-March 2008 (table 8).

Table 8 Therapeutic efficacy drug for the treatment of salmonellosis in young farm animals Indicators Group of animals The control Experience Number of animals, goals 47 47 Recover, Goals 41 43 % 87.2 91.5 Fallen, goals 3 0 % 6.4 0 Stayed sick goals 3 four % 6.4 8.5 Duration of recovery, days 5.7 ± 0.7 4.2 ± 0.5 Therapeutic efficacy,% 87.2 91.5

Studies have shown that the drug for the treatment of salmonellosis in young farm animals has high therapeutic efficacy in the treatment of salmonellosis in calves (on average, it was 90.9%), which is 8.6% higher than the effectiveness of enroxil 5%, and 4.3 % above a solution of gentamicin sulfate 4% (third experiment). Compared with the control groups, when using the drug for the treatment of salmonellosis in young farm animals, there were no cases of animals; the recovery period decreased by an average of 24.2%.

Example 4. The study of the effectiveness of the treatment of salmonellosis in piglets.

The study was carried out in three experiments on pigs 30-35 days of age. According to the principle of paired analogues, the animals were divided into two groups, taking into account the general condition and severity of the disease and under the same conditions of feeding and keeping.

The diagnosis of colibacteriosis was made comprehensively on the basis of data from a clinical examination of animals, the results of bacteriological studies (cultures of Salmonella typhimurium and Salmonella cholerae suis were isolated and studied during bacteriological examination of faeces), pathological autopsy taking into account the epizootic situation on the farm.

The animals were monitored daily for 15 days, taking into account the general condition, death, growth rate, and timing of recovery.

Piglets of the control group were treated with 5% enroxil produced by KRKA (Slovenia), which was administered subcutaneously at a dose of 1 ml / 20 kg of body weight 1 time per day for 3-5 days.

For the animals of the experimental group, a preparation was used to treat salmonellosis in young farm animals in the following ratio of components, wt.%:

Colistin sulfate - 5.0;

Tylosin base - 5.0;

Sodium pyrosulfite - 0.32;

Water for injection - 15.0;

Benzyl alcohol - 4.0;

1,2-Propylene glycol - up to 100.0%.

The drug for the treatment of salmonellosis in young farm animals was used intramuscularly at a dose of 0.075 ml / kg body weight three times with an interval of 24 hours. In severe cases of the disease, four to five injections were performed at intervals of 24 hours.

The first experience in studying the effectiveness of treatment of salmonellosis of piglets was carried out in LLC “im. Gorky "Dep. Revival ”of the Gryazinsky district of the Lipetsk region in October-December 2007. The second experiment was conducted at the Rotar Farm in the Ostrogozhsky District of the Voronezh Region in January-February 2008. The third experiment was carried out in FE “Sorokina OV”, Talovsky District, Voronezh Region in February-March 2008.

The results of experiments to study the effectiveness of the treatment of salmonellosis in piglets are presented in tables 9-11.

Table 9 The effectiveness of the treatment of salmonellosis in piglets in LLC “them. Gorky "Dep. Revival "Gryazinsky district of the Lipetsk region Indicators Group of animals The control Experience Number of animals, goals 54 57 Recover, Goals 46 53 % 85,2 93.0 Fallen, goals 3 one % 5,6 1.7 Stayed sick goals 5 3 % 9.2 5.3 Duration of recovery, days 4.8 ± 0.2 4.3 ± 0.3 Therapeutic efficacy,% 85,2 93.0

Table 10 The effectiveness of treatment of salmonellosis in piglets in the farm "Rotar" Ostrogozhsky district of Voronezh region Indicators Group of animals The control Experience Number of animals, goals 120 138 Recover, Goals 98 132 % 81.7 95.7 Fallen, goals 6 0 % 5,0 0 Stayed sick goals 16 6 % 13.3 4.3 Duration of recovery, days 4.9 ± 0.6 4.1 ± 0.4 Therapeutic efficacy,% 81.7 95.7

Table 11 The effectiveness of the treatment of salmonellosis in piglets in IE "Sorokina OV" Talovsky district of Voronezh region Indicators Group of animals The control Experience Number of animals, goals 130 138 Recover, Goals 113 130 % 86.9 94.4 Fallen, goals 5 2 % 3.9 1,5 Stayed sick goals 12 6 % 9.2 4.3 Duration of recovery, days 5.1 ± 0.7 4.8 ± 0.6 Therapeutic efficacy,% 86.9 94.2

As studies have shown, the drug for the treatment of salmonellosis in young farm animals has high therapeutic efficacy in the treatment of salmonellosis in piglets (an average of 94.4%). In all experiments, when using the drug for the treatment of salmonellosis in young farm animals, the recovery time was reduced by 0.3-0.8 days compared with the control groups, the mortality of animals decreased by 4.4 times.

Example 5. Toxicological safety of the drug for the treatment of salmonellosis in young farm animals.

According to the existing regulation on medicines intended for the treatment of animals, an experimental preclinical study of the pharmacological activity and toxicological properties of the drug for the treatment of salmonellosis in young farm animals was carried out.

During the research, pharmacological, toxicological, biochemical, pathomorphological research methods used to study drugs were used, which have been tested in research practice.

The experiments were carried out on sexually mature conventional non-linear heterosexual white mice weighing 20-22 g (191 goals) and white rats weighing 200-225 g (132 goals), breeding vivarium of the All-Russian NIVI pathology, pharmacology and therapy. Animals were kept in vivarium conditions at 20-22 ° C and humidity 40-60%. Keeping animals and providing food was in compliance with the regulatory requirements of the International Convention.

Determination of the toxicity parameters of the drug for the treatment of salmonellosis in young farm animals in an acute experiment was carried out with a single oral, intramuscular and subcutaneous administration in two types of laboratory animals: white mice and white rats.

Groups of animals were formed according to the principle of paired analogues, taking into account body weight, development and clinical condition. Before the start of the experiments, the animals were quarantined for 12 days, and before the administration of the drug they were not fed for 12 hours.

Observation of animals was carried out continuously during the first day after administration of the drug. In the subsequent state of the animals was noted twice a day for 14 days. We recorded the general status and behavior of animals, the state of neuromuscular and vegetative functions, coat, eating food, and water consumption. Particular attention was paid to the development of signs of toxicosis, their severity, duration, time of recovery or death of animals was evaluated.

The drug was administered once inside at doses from 4000.0 to 18000.0 mg / kg body weight (white mice) and from 3500.0 to 17500.0 mg / kg (white rats). With a single intramuscular injection, the drug was administered in doses from 500.0 to 1700.0 mg / kg (white mice) and from 450.0 to 1700.0 mg / kg (white rats). With a single subcutaneous injection, the drug was administered in doses from 950.0 to 1950.0 mg / kg (white rats).

As a result of the studies, it was found that a single intragastric administration of the drug in doses of 4000.0 and 3500.0 mg / kg body weight, intramuscular injection in doses of 500.0 and 450.0 mg / kg and subcutaneous administration in doses of 950.0 mg / kg did not cause a clinical picture of toxicosis in white mice and rats, the death of animals was not observed. With a further increase in the administered dose, the death of animals was noted. The latent period of poisoning lasted 15-90 minutes, depending on the dose administered. Death usually occurred during the first day, and with the introduction of high doses - after 1.0-1.5 hours.

Based on the results of primary toxicometric studies, the parameters of acute toxicity of the drug for the treatment of salmonellosis in young farm animals were obtained (table 12).

Table 12 Parameters of acute toxicity of the drug for the treatment of salmonellosis in young farm animals Type of belly
ny Toxicity parameters (mg / kg) SLD ₅₀ MTD LD ₁₆ LD ₅₀ LD ₈₄ LD ₁₀₀ intragastric administration white mice 4000,0 6875.1 10903.0 (9160-12600) 14795.7 18000.0 ± 863.0 white rats 3,500.0 6209.2 10702.6 (9190-12200) 15260.8 17500.0 ± 754.3 intramuscular injection white mice 500,0 576.2 1038.0 (849-1230) 1454.4 1700.0 ± 92.4 white rats 450,0 622.1 1033.8 (807-1260) 1428.3 1700.0 ± 109.7 subcutaneous administration white rats 950.0 1089.1 1421.1 (1210-1630) 1733.7 1894.8 ± 99.2

The clinical symptoms of acute poisoning of white mice and white rats were accompanied by a short period of excitement with increased motor activity in most individuals. Rats showed aggressiveness. Over a short period of excitement, sharply expressed oppression developed, a state of deep sleep, then turning into a coma. Animals did not respond to light and tactile stimuli. At the time of the death of the animals, rapid breathing and palpitations were noted. Breathing often became superficial, intermittent, cyanosis of the skin and mucous membranes developed. Death, as a rule, occurred in a state of deep oppression.

Thus, based on the results obtained in acute experience, we can say that the drug in accordance with GOST 12.1.007-76 in terms of toxicity belongs to hazard class IV - low-hazard substances.

In a subacute experiment conducted on white male rats weighing 160-180 g with an intramuscular injection of the drug for 21 days, it was found that repeated intramuscular administration of the drug for the treatment of salmonellosis in young farm animals at doses of 0.05 ml / kg and 0 , 20 ml / kg body weight (1/20 and 1/50 of the dose of LD ₅₀ established in the acute toxicity study) does not cause significant changes in the clinical condition of animals: behavior, grooming, appetite, respiratory rate in all experimental animals groups as in In the course of development of the drug, and within one week after the end of the use of the drug for the treatment of salmonellosis in young farm animals remained within the physiological norm. There were also no cases of death of animals.

During the observation period in animals of the experimental groups, there were no violations of the digestive and urinary functions. The rats of the experimental groups remained mobile, they did not show a violation of appetite, the reflexes were preserved.

It was found that the drug for the treatment of salmonellosis in young farm animals has an effect on the growth rate of animals.

When examining the blood of animals that were injected with the drug for the treatment of salmonellosis in young farm animals at doses of 0.05 ml / kg body weight, there were no significant changes in the morphological composition of blood and biochemical parameters compared with the blood parameters of animals in the control group (table 13 and 14).

Table 13 Morphological blood parameters of white rats with repeated intramuscular use of the drug for the treatment of salmonellosis in young farm animals (after 21 days) Indicators The control Doses of the drug for the treatment of salmonellosis in young farm animals, ml / kg 0.05 0.20 Red blood cells, 10 ¹² / L 5.42 ± 0.02 5.63 ± 0.09 5.37 ± 0.07 White blood cells, 10 ⁹ / L 5.55 ± 0.12 6.33 ± 0.71 5.47 ± 0.07 Hemoglobin, g / l 116.8 ± 0.71 122.2 ± 2.13 118.5 ± 2.97 Hematocrit, g / l 38.0 ± 0.58 41.3 ± 1.20 41.0 ± 2.00 Neutrophils,% - - - Segmented 18.0 ± 2.91 18.0 ± 3.46 24.0 ± 7.00 Eosinophils,% 2.75 ± 1.44 1.33 ± 0.08 1.33 ± 0.33 Basophils,% - - - Lymphocytes,% 77.5 ± 2.99 76.3 ± 3.71 64.7 ± 7.67

Table 14 Biochemical blood parameters of white rats with repeated intramuscular administration of a drug for the treatment of salmonellosis in young farm animals (after 21 days) Indicators The control Doses of the drug, ml / kg 0.05 0.20 Total protein, g / l 66.9 ± 0.91 69.5 ± 0.33 74.6 ± 1.02 Albumin, g / l 33.6 ± 0.16 33.8 ± 0.10 43.2 ± 0.35 * Urea, mmol / l 5.35 ± 0.22 5.59 ± 0.06 7.51 ± 0.84 * Glucose, mmol / l 9.65 ± 0.59 9.78 ± 0.07 10.13 ± 0.21 Cholesterol, mmol / l 1.28 ± 0.11 1.42 ± 0.15 1.75 ± 0.04 Total lipids, g / l 2.31 ± 0.12 2.24 ± 0.07 2.46 ± 0.07 AsAT, Unit / L 106.7 ± 4.94 119.5 ± 22.5 134.2 ± 5.18 * AlAT, Unit / L 39.25 ± 1.41 35.67 ± 1.78 52.96 ± 1.97 * Creatinine, μmol / L 26.5 ± 0.87 21.3 ± 4.66 30.0 ± 3.60 Alkaline phosphatase, U / l 282.5 ± 12.4 372.0 ± 26.3 * 475.3 ± 6.33 * Phosphorus, mM / L 2.33 ± 0.02 2.82 ± 0.12 2.76 ± 0.16 Calcium, mmol / l 2.38 ± 0.08 2.37 ± 0.02 2.48 ± 0.07 ^* P <0.05 - 0.001 compared with the control.

With an increase in the dose of the drug for the treatment of salmonellosis in young farm animals (0.20 ml / kg), there was a steady tendency to more intense functioning of the excretory system and liver. With 21-day intramuscular administration of the drug at a dose of 0.20 ml / kg body weight in rats of the experimental group, the urea content in the blood serum increased significantly - by 40.4%, albumin - by 28.6%, the activity of AlAT, AsAT - by 34 , 9 and 25.8%, respectively, of alkaline phosphatase - 1.7 times. However, the average value of these indicators in rats of the experimental group did not go beyond the upper limits of the norm for this animal species. 10 days after the last injection of the drug, these parameters in experimental animals were restored to physiological values.

When studying the cumulative ability of the drug according to the Lima method, fractional administration of the drug to white rats in increasing doses did not cause the death of animals. Due to the absence of death of 50% of experimental rats, the cumulation coefficient was impossible to calculate. But, given that the administered doses are 12.7 LD ₅₀ , the possible cumulation coefficient exceeds 12. This indicates the absence of a cumulative effect in the drug.

When studying the subchronic toxicity of the drug in doses of 0.05 and 0.15 ml / kg body weight for 14 days with an interval between administrations of 24 hours spent on pigs and calves, it was found that its intramuscular administration in the studied doses did not significantly affect Clinical status, behavior and appetite of animals. During the whole experiment, both the piglets and the calves of the control and experimental groups were mobile, the appetite was expressed, the reflexes were preserved. Violations of the digestive and urinary functions have not been established. The drug in various doses did not reduce the growth rate of animals.

With repeated use of the drug, the morphological and biochemical parameters of blood did not significantly differ from those in animals of the control group.

Thus, the tests of the drug for the treatment of salmonellosis in piglets and calves showed that it has a wide spectrum of antimicrobial action, a pronounced therapeutic effect in salmonellosis in piglets and calves, is low toxic. The use of the drug is technologically and cost-effective.

Claims (1)

A drug for the treatment of salmonellosis in young farm animals, containing colistin sulfate and an antibiotic from the macrolide group, characterized in that it additionally contains sodium pyrosulfite, benzyl alcohol, water for injection and 1,2-propylene glycol, and tylosin base is used as an antibiotic of the macrolide group in the following ratio of components, wt.%:
Colistin sulfate 4.0-6.0 Tylosin base 4.0-6.0 Sodium pyrosulfite 0.32 Benzyl alcohol 4.0 Water for injections 15.0 1,2-propylene glycol Up to 100.0