RU2354353C1 - Preparation for treatment of colibacillosis in young agricultural animals - Google Patents

Abstract

FIELD: pharmacology, veterinary medicine.

SUBSTANCE: invention is related to the field of veterinary. Preparation consists of the following components, wt %: Gentamicin sulfate - 3.5-4.5, Dioxidin - 0.5-1.5, Disodium salt ethylene diamine -N,N,N',N'-of tetraacetic acid 2-hydrate - 0.01, Water for injections - up to 100. Prior to application preparation is heated up to 37-38°C and injected intramuscularly daily twice in dose of 0.1 ml/kg of body weight for 3-5 days, in case of serious run of disease - for 5-7 days.

EFFECT: increased efficiency of colibacillosis treatment, fast recovery of sick animals, reduced consumption of active substances and their side effect at organism.

10 tbl, 4 ex

Description

The invention relates to the field of veterinary medicine.

Despite the significant achievements of veterinary science, bacterial infections of farm animals continue to cause significant damage to specialized farms: even in case of satisfactory zoohygienic conditions, up to 50-70% of the livestock are ill with them. In severe forms of the disease, mortality can reach 90% of the total number of sick animals.

The specific prevention of many bacterial infections is not effective enough, therefore, the leading role in the fight against them belongs to chemotherapeutic drugs, in particular antibiotics, sulfonamides, nitrofurans.

The problem of antibiotic therapy in intensive animal husbandry is that pharmaceutical companies actually do not develop fundamentally new molecules, as is the case in medicine. Most successfully, this problem is solved by using combination antibiotic therapy.

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.

Known analogue - the drug "Diarin" - for the treatment and prevention of gastrointestinal diseases of young animals, which contains, wt.%: Dioxidine 0.6-0.9, 40% lactic acid 10.0-15.0, methyluracil 0.6-0.9, boiled water - the rest [RU 2105548 C1, 02.27.1998.].

A known tool for the treatment of gastrointestinal diseases of young farm animals "Diacetin" containing antibacterial dioxidine, anti-inflammatory and antipyretic agent - acetylsalicylic acid, immunomodulating agent thymalin and natural zeolites in the following ratio, wt.%: Dioxidine - 2.5-5, 0, acetylsalicylic acid - 25.0-75.0, thymalin - 0.5-0.75, zeolites - up to 100 [RU 2075972 C1, 03/27/1997.].

A well-known analogue is the drug Enroxil - 5% solution for injection is a clear yellow solution, 1 ml of which contains 50 mg of enrofloxacin. [Veterinary Medicines 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].

However, the use of these drugs does not always lead to positive results. On the one hand, apparently, this is due to the development of resistance of the pathogen to drugs. 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 prototype - gentamicin sulfate 4% - is a mixture of several antibiotics produced by Micromonospora purpurea. Available in the form of a sterile solution containing 40 mg of active substance in 1 ml. In the treatment of colibacteriosis in cattle and pigs, a solution of 4% gentamicin sulfate is administered intramuscularly twice a day with an interval of 10-12 hours, respectively, at doses of 3.0 and 4.0 mg / kg body weight [Veterinary preparations in Russia: Reference in 2 volumes. T.1. / I.F.Klenova, K.L. Maltsev, N.A. Yaremenko, I.A. Arkhipov. - M .: Selkhozizdat, 2004. - S.168-169.].

A well-known drug is not always effective enough and leads to the complete recovery of all sick piglets in the presence of a side effect (nephro-and ototoxicity).

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

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

The technical result is achieved using the drug, consisting of the following components, wt.%:

Gentamicin sulfate - 3.5-4.5,

Dioxidine - 0.5-1.5,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

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

Gentamicin sulfate - 4,

Dioxidine - 1,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

The validity of this combination is due to the fact that two bactericidal agents are simultaneously combined in the dosage form. This provides a synergistic effect due to the fact that these drugs act in the same phase of cell growth, but on different metabolic pathways.

Dioxidine - a quinoxaline drug - 1,4-di-N-oxide-2,3-di (oxymethyl) quinoxaline [Chervyakov D.K. et al. Medicines in veterinary medicine. - M .: Kolos, 1977, S. 215]. The antibacterial action of dioxidine is based on the selective suppression of DNA synthesis. In addition, the drug reduces the activity of extracellular nuclease and plasmocoagulase in microorganisms, which leads to dysfunction of the genetic apparatus of the microbial cell and, as a result, the biosynthesis of biologically active macromolecules, which are pathogenicity factors, is suppressed.

Gentamicin sulfate - an aminoglycoside inhibits bacterial protein synthesis. It has a wide spectrum of antibacterial action, is active against gram-positive and gram-negative microorganisms (staphylococci, clostridia, proteus, etc.). The mechanism of action of gentamicin is associated with impaired synthesis of microbial cell polypeptides in ribosomes [British Pharmacopoeia, 2000, V.1, p.638].

The main purpose of the combined use of dioxidine and gentamicin 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 disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous (Trilon B) is a white crystalline powder and white crystals, highly soluble in water, very slightly soluble in alcohol. The empirical formula is C ₁₀ H ₁₄ O ₈ N ₂ Na ₂ · 2H ₂ O. The relative molecular weight (by international atomic masses of 1985) is 372.24 [Reagents. The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous (Trilon B). Technical conditions GOST 10652-73 - M .: IPK Standards Publishing House, 1999. - 14 p.].

Water for injection is obtained by distillation or osmosis. It is pyrogen-free, does not contain antimicrobial agents 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 March 11, 1997. - 4 p.].

The drug for the treatment of colibacteriosis in young farm animals is heated to 37-38 ° C before use. The drug is administered intramuscularly daily twice a day at a dose of 0.1 ml / kg body weight 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 simultaneous or sequential use of the drug for the treatment of colibacteriosis in young farm animals with other oto- and nephrotoxic drugs (streptomycin, kanamycin, neomycin), as well as in severe renal impairment, is not allowed.

The drug is contraindicated in animals with hypersensitivity to gentamicin and dioxidine. Slaughter of animals for meat is allowed no earlier than 21 days after the last injection of the drug. The meat of animals forcibly 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 colibacteriosis in young farm animals as follows. Water for injection is heated in a reactor with a contact thermometer and loop heating and cooling to a temperature of (50 ± 5 ° C). Then, disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous, dioxidine and gentamicin sulfate are introduced sequentially into the reactor at intervals 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 filling units, when filling 20-10 ml - every 300 filling units, when filling in ampoules - every 500 filling 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 colibacteriosis in young farm animals, the study of its antimicrobial properties.

The antimicrobial properties of the drug were studied. The optimal quantitative content of gentamicin and dioxidine 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.

1.1. In vitro experiments

The study of the antimicrobial activity and the ratio of gentamicin and dioxidine in the drug for the treatment of colibacteriosis in young farm animals was carried out in vitro by the method of serial dilutions. As test cultures, reference and field (pathogenic) strains of microorganisms - pathogens of gastrointestinal diseases of piglets and calves typified by morphological, tinctorial, cultural, biochemical and serological properties were used. The ratio of gentamicin and dioxidine in the drug for the treatment of colibacteriosis in young farm animals in the following combinations:

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

Gentamicin sulfate - 3.5,

Dioxidine - 1.5,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

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

Gentamicin sulfate - 4,

Dioxidine - 1,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

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

Gentamicin sulfate - 4.5,

Dioxidine - 0.5,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

The antimicrobial activity of various combinations of the composition of the drug was compared with the antimicrobial activity of gentamicin and dioxidine.

The minimum bacteriostatic concentration (MBsK) of the studied drugs was determined by the method of serial dilutions in meat and peptone broth (MPB); 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. When determining the sensitivity of streptococci to the medium, 1% glucose was added.

The main solution of the drug is 1000 μg / ml (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 and peptone broth were poured into 16 sterile tubes. 4.5 ml of the drug 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 culture growth, a 16 test tube containing no preparation was used.

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 the studies are presented in table 1.

In relation to Escherichia in terms of the absolute weight of the preparation, the activity of the gentamicin-dioxidine composition at a ratio of 4.0: 1.0 percent remained virtually unchanged compared with the activity of gentamicin, and increased 2-4 times in comparison with the activity of dioxidine. The antimicrobial activity of the compositions of gentamicin with dioxidine at a ratio of 4.5: 0.5 and 3.5: 1.5 as a percentage compared to gentamicin decreased on average 1.4 and 2.6 times, respectively, but increased compared to dioxidine 3.7 and 2 times. At the same time, the combined use of gentamicin and dioxidine reduced the BMD for gentamicin to 0.12-1.10 μg / ml, for dioxidine - to 0.02-0.38 μg / ml.

The most resistant to the studied drugs was Pseudomonas aeruginosa. In relation to this microorganism, by the absolute weight of the preparation, the activity of the composition of gentamicin with dioxidine at ratios in percentages of 4.0: 1.0 and 4.5: 0.5 did not change compared with the activity of gentamicin, and compared with the activity of dioxidine . The antimicrobial activity of the compositions of gentamicin with dioxidine at a percentage ratio of 3.5: 1.5 compared to gentamicin decreased by 2 times, but did not change compared to dioxidine. Concerning Pseudomonas aeruginosa, the combined use of gentamicin and dioxidine reduced the BMD for gentamicin to 1.0-1.1 μg / ml, for dioxidin - to 0.13-0.25 μg / ml.

Thus, the study of the antimicrobial activity of the combinations of gentamicin and dioxidine showed the presence of a synergistic effect in relation to the studied pathogenic cultures.

Table 1 Antimicrobial activity of gentamicin, dioxidine and various compositions of the drug for the treatment of colibacteriosis in young farm animals (μg / ml) Microorganism culture Gentamicin Dioxidine Combination 1 Combination 2 Combination 3 MBSK MBCC MBSK MBCC MBSK MBCC MBSK MBCC MBSK MBCC Escherichia coli 57358 3.12 6.25 25.0 50,0 6.25 12.5 6.25 12.5 3.12 6.25 Escherichia coli O4 6.25 12.5 12.5 25.0 12.5 25.0 6.25 12.5 6.25 12.5 Escherichia coli O139 (p) 12.5 25.0 50,0 100.0 25.0 50,0 6.25 12.5 6.25 12.5 Escherichia coli 866 3.12 6.25 25.0 50,0 12.5 25.0 3.12 6.25 3.12 6.25 Escherichia coli O (III) (p) 6.25 12.5 50,0 100.0 25.0 50,0 12.5 25.0 25.0 50,0 Pseudomonas aeruginosa 25.0 50,0 50,0 200,0 50,0 100.0 25.0 50,0 25.0 50,0

1.2. In vivo experiments

The efficacy of gentamicin and dioxidine, as well as these components in various ratios, was determined in model experiments during experimental infection of white mice with Salmonella cholerae suis 434/9 (2.25 million m3 / mouse), Escherichia coli 57358 (2.5 billion M.C. / mouse).

The experiments were performed on sexually mature conventional non-linear heterosexual white mice weighing 20-22 g (400 animals), 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.

Groups of animals were formed according to the principle of paired analogues of 16 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 10 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.

Treatment of mice was started 6 hours after infection. The drugs were administered 2 times a day intramuscularly.

The therapeutic efficacy of the selected drug combinations was judged by the number of surviving mice after treatment and the number of mouse days for each group 10 days after infection (see table 2).

Given the results obtained in experiments in vitro in experiments in vivo, two combinations of gentamicin and dioxidine were tested:

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

Gentamicin sulfate - 4,

Dioxidine - 1,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

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

Gentamicin sulfate - 4.5,

Dioxidine - 0.5,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

table 2 Therapeutic activity of gentamicin and dioxidine and their combinations in experimental infection of white mice Microorganism pathogen A drug Dose, mcg / mouse The number of mice in the group It’s fallen, a goal. Survived Mouse-days of life Goal. % Salmonella cholerae suis 434/9 (2.25 million m3 / mouse) The control - 16 16 0 0 51 Gentamicin 80.0 16 four 12 75.0 147 Dioxidine 20,0 16 6 10 62.5 131 Combination 1 80.0 + 20.0 16 2 fourteen 87.5 155 Combination 2 90.0 + 10.0 16 2 fourteen 87.5 157 Escherichia coli 57358
(2.5 billion sq.m. / mouse) The control - 16 16 0 0 fifty Gentamicin 80.0 16 7 9 56.3 138 Dioxidine 20,0 16 7 9 56.3 120 Combination 1 80.0 + 20.0 16 four 12 75.0 150 Combination 2 90.0 + 10.0 16 four 12 75.0 146

As can be seen from the data presented in table 2, the treatment of experimental infections with gentamicin at a dose of 80 μg / mouse is ineffective (the effectiveness of the drug is 56.3-81.3%). The treatment of experimental infections caused by Salmonella cholerae suis 434/9, Escherichia coli 57358 with dioxidine at a dose of 20 μg / mouse is also ineffective (the effectiveness of the drug is 56.3-62.5%).

During experimental infection of mice with Salmonella cholerae suis 434/9, treatment with a drug for the treatment of colibacteriosis in young farm animals at doses of 80 + 20 and 90 + 10 μg / mouse ensured the safety of animals within 87.5%, which was 12.5-25 higher % compared with gentamicin and 25-68.7% with dioxidine.

The efficacy of complexes of gentamicin and dioxidine in doses of 80 + 20 and 90 + 10 μg / mouse in the treatment of white mice infected with Escherichia coli 57358 was 18.7% higher compared to the separate use of dioxidine and gentamicin.

An increase in the total life expectancy of white mice depending on the pathogen microorganism by 8-70 days was also noted in the groups treated with the drug for the treatment of colibacteriosis in young farm animals.

Studies have shown that the drug for the treatment of colibacillosis 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 gentamicin in combination with dioxidine 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 complexes of gentamicin and dioxidine ensured the safety of animals from 75 to 100%, depending on the pathogen microorganism.

Example 2. The study of the effectiveness of the treatment of colibacteriosis in calves.

The study was carried out in four experiments on calves 1-10 days of age weighing 30-40 kg. According to the principle of paired analogues, animals were divided into two groups.

The diagnosis of colibacteriosis was made comprehensively on the basis of data from a clinical examination of animals, bacteriological studies (E. coli of various serological variants were highlighted), pathological autopsy, 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 1, 2, 3, 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. In the fourth experiment, the calves of the control group were treated with 5% enroxil manufactured 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 colibacteriosis in young farm animals in the following ratio of components, wt.%:

Gentamicin sulfate - 4,

Dioxidine - 1,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

The drug was administered intramuscularly at a dose of 1 ml / 10 kg of body weight with an interval of 12 hours for 2-3 days, with severe illness - for 3-5 days.

The first experience in studying the effectiveness of the treatment of calf colibacteriosis was carried out in OAO Yubileinoye, Khokholsky District, Voronezh Region, in March - May 2004.

The second experience in studying the effectiveness of treatment of calf colibacteriosis was carried out in Yubileinoe OJSC of the Khokholsky District of the Voronezh Region in January - March 2005.

The third experience in studying the effectiveness of parenteral administration for the treatment of colibacteriosis in calves was carried out in Novaya Derevnya LLC, Lipetsk region, Lipetsk region in April - May 2004.

The fourth experience in studying the effectiveness of the treatment of colibacillosis in calves was carried out in the SEC "Staronikolsky" of the Khokholsky district of the Voronezh region in February 2007.

The results of the experiments are presented in tables 3-6.

Table 3 The effectiveness of the treatment of colibacillosis in OAO Yubileinoye, Khokholsky District, Voronezh Region (1st experiment) Indicators Group of animals The control Experience Number of animals, goals 93 97 Recover, Goals 78 92 % 83.9 94.9 Fallen, goals 2 2 % 2.2 2.0 Stayed sick goals 13 3 % 13.9 3,1 Duration of recovery, days 4.0 ± 0.5 3.4 ± 0.4 Therapeutic efficacy,% 83.9 94.9 Table 4 The effectiveness of the treatment of colibacillosis in OAO Yubileinoye, Khokholsky District, Voronezh Region (2nd experiment) Indicators Group of animals The control Experience Number of animals, goals 80 82 Recover, Goals 68 75 % 85.0 91.5 Fallen, goals four 2 % 5,0 2,4 Stayed sick goals 8 5 % 10.0 6.1 Duration of recovery, days 4.4 ± 0.3 3.6 ± 0.3 Therapeutic efficacy,% 85.0 91.5

Table 5 The effectiveness of the treatment of colibacteriosis of calves in LLC "New Village" of the Lipetsk region of the Lipetsk region (3rd experience) Indicators Group of animals The control Experience Number of animals, goals 58 63 Recover, Goals 48 59 % 82.8 93.6 Fallen, goals 2 one % 3.4 1,6 Stayed sick goals 8 3 % 13.8 4.8 Duration of recovery, days 4.3 ± 0.5 3.9 ± 0.3 Therapeutic efficacy,% 82.8 93.6 Table 6 The effectiveness of the treatment of colibacillosis in the SEC "Staronikolsky" of the Khokholsky district of the Voronezh region (4th experiment) Indicators Group of animals The control Experience Number of animals, goals eleven 19 Recover, Goals 10 19 % 91.0 100.0 Fallen, goals one 0 % 9.0 0 Stayed sick goals 0 0 % 0 0 Duration of recovery, days 6.2 ± 0.3 5.1 ± 0.2 Therapeutic efficacy,% 91.0 100.0

Studies have shown that the drug for the treatment of colibacteriosis in young farm animals has high therapeutic efficacy in the treatment of colibacteriosis in calves (on average it was 93.3%), which is 9.4% higher than the efficiency of the gentamicin sulfate solution 4%, and 9 , 0% - above enroxil 5% (fourth experiment). Compared with the control groups, when using the drug for the treatment of colibacteriosis in young farm animals, the death rate of animals decreased by an average of 3.3 times, the recovery time decreased by an average of 14.9%.

Example 3. The study of the effectiveness of the treatment of colibacteriosis in piglets.

The study was carried out in three experiments on pigs of 2-10 days of age weighing 2.5-3.5 kg. 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 a bacteriological study (Escherichia coli of various serological variants were identified), postmortem autopsy, 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.

Piglets of the control group were treated with a solution of gentamicin sulfate 4%, which was administered intramuscularly at a dose of 4 mg / kg body weight twice a day for 3-5 days.

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

Gentamicin sulfate - 4,

Dioxidine - 1,

The disodium salt of ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous - 0.01,

Water for injection - up to 100%.

The drug was administered intramuscularly at a dose of 1 ml / 10 kg of body weight with an interval of 12 hours for 2-3 days, with severe illness - for 3-5 days.

The first experience in studying the effectiveness of the treatment of colibacillosis of piglets was carried out in the SCA "Beginning" Rossoshansky district of the Voronezh region in September - October 2004. The second experiment was conducted in the SCA "Beginning" Rossoshansky district of Voronezh region in January - February 2005.

The third experiment was carried out by the Liven Meat OJSC Agrofirm of the Liven district of the Oryol Region in February - March 2007.

The results of experiments to study the effectiveness of the treatment of colibacteriosis in piglets are presented in table 7-9.

Table 7 The effectiveness of the treatment of colibacillosis in piglets in the SCA "Beginning" Rossoshansky district of the Voronezh region Indicators Group of animals The control Experience Number of animals, goals 93 106 Recover, Goals 81 99 % 87.1 93,4 Fallen, goals four 3 % 4.3 2,8 Stayed sick goals 8 four % 8.6 3.8 Duration of recovery, days 4.9 ± 0.6 4,5 ± 0,6 Therapeutic efficacy,% 87.1 93,4 Table 8 The effectiveness of the treatment of colibacillosis in piglets in the SCA "Beginning" Rossoshansky district of the Voronezh region Indicators Group of animals The control Experience Number of animals, goals 76 98 Recover, Goals 67 95 % 88.2 96.9 Fallen, goals 2 one % 2.6 1,0 Stayed sick goals 7 2 % 9.2 2.0 Duration of recovery, days 5.7 ± 0.6 4.1 ± 0.6 Therapeutic efficacy,% 88.2 96.9

Table 9 The effectiveness of the treatment of colibacteriosis in piglets in JSC Agrofirm "Liven meat" Liven district of the Oryol region Indicators Group of animals The control Experience Number of animals, goals 53 56 Recover, Goals 53 56 % 100.0 100.0 Fallen, goals 0 0 % 0 0 Stayed sick goals 0 0 % 0 0 Duration of recovery, days 4.9 ± 0.2 3.9 ± 0.3 Therapeutic efficacy,% 100.0 100.0 The average daily weight gain, g 73.5 ± 4.2 104.0 ± 4.03

As the studies showed, the drug for the treatment of colibacillosis in young farm animals has high therapeutic efficacy in the treatment of colibacillosis in piglets (96.8% on average). In all experiments, when using the drug for the treatment of colibacteriosis in young farm animals, the recovery time was reduced by 0.4-1.6 days compared with the control groups, the mortality of animals decreased by 1.5 times.

Example 4. Toxicological safety of the drug for the treatment of colibacillosis in young farm animals.

According to the existing regulation on medicines intended for the treatment of animals, an experimental preclinical study of the general pharmacological activity and toxicological properties of the drug for the treatment of colibacteriosis 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 colibacteriosis in young farm animals in an acute experiment was carried out with a single oral, intramuscular and intraperitoneal 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.

In the first series of experiments, the acute toxicity of the drug for the treatment of colibacteriosis in young farm animals was tested with the oral route of administration. The drug was administered once inside at doses of 5000.0 to 50,000.0 mg / kg body weight in a volume of 0.6 ml per mouse and 6.0 ml per rat (doses are extremely acceptable in volume for oral administration). Higher doses for white mice and white rats over 25,000 mg / kg were administered in two doses, half the dose at intervals of 2 hours. The volume of the drug solution administered to the animals was adjusted to the required volume by adding water for injection to the preparation. The death of animals with the introduction of the drug in the studied doses for the entire period of observation of animals (14 days) was not observed. According to the degree of toxicity, the drug belongs to hazard class IV - low-hazard substances [GOST 12.1.007-76].

In the second and third series of experiments on the study of acute toxicity of the drug, doses from 4000.0 to 10000.0 mg / kg (mice) and from 4500.0 to 12000.0 mg / kg (rats) were tested with intraperitoneal and intramuscular administration - from 4500.0 to 10500.0 mg / kg (mouse) and from 4500.0 to 12000.0 mg / kg (rat).

Based on the results of toxicometric studies, the following parameters of the acute toxicity of the drug for the treatment of colibacteriosis in young farm animals were obtained, which are presented in table 10.

Table 10 Parameters of acute toxicity of the drug for the treatment of colibacteriosis in young farm animals with a single parenteral administration for laboratory animals (mg / kg) Animal species Toxicity parameters SLD ₅₀ MTD LD ₁₆ LD ₅₀ LD ₈₄ LD ₁₀₀ Intraperitoneal administration White mice 4000,0 5650.0 7177.8 (6090-8260) 7610.0 10,000.0 ± 529.6 White rats 4,500.0 5770.0 8810.0 7250-10400 8610,0 12000.0 ± 750.2 Intramuscular injection White mice 4,500.0 5643.3 7078.3 (6310-7850) 8,409.6 10500.0 ± 375.5 White rats 4,500.0 6021,2 8,249.6 (6950-9550) 10479.2 12000.0 ± 629.6

The clinical symptoms of acute poisoning of white mice and white rats with both intraperitoneal and intramuscular administration were accompanied by a short period of excitation with an increase in 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.

In a subacute experiment, which was performed 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 colibacteriosis in young farm animals at doses of 0.16 ml / kg; 0.40 ml / kg and 0.80 ml / kg of body weight (1/50; 1/20; 1/10 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 animals of the experimental groups both during the period of use of the drug and within one week after the use of the drug for the treatment of colibacteriosis 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 disturbances in the functions of digestion and urination. The rats of the experimental groups remained mobile, they did not have a loss of appetite, the reflexes were preserved.

It was found that the drug for the treatment of colibacillosis in young farm animals has an effect on the growth rate of animals. At the same time, the dependence of this effect on the administered dose of the drug is traced. So, at a dose of 0.16 ml / kg, the drug stimulates the growth of animals by an average of 6.7%. During the course of drug administration, experimental animals that were administered the drug for the treatment of colibacteriosis in young farm animals at a dose of 0.4 ml / kg did not differ from the control in terms of body weight gain and at the end of the experiment no statistically significant differences were found for this indicator.

In rats to which the drug was administered intramuscularly at a dose of 0.80 ml / kg body weight, throughout the experiment, a decrease in body weight gain relative to the control was observed, which indicates the toxic effect of the drug. However, 10 days after the last injection of the drug for the treatment of colibacteriosis in young farm animals, the average daily weight gain of rats approaches the average daily weight gain of control animals (see table 11).

Table 11 Morphological parameters of blood of white rats with repeated intramuscular use of the drug for the treatment of colibacteriosis in young farm animals Indicators The control Doses of the drug for the treatment of colibacteriosis in young farm animals, ml / kg 0.16 0.40 0.80 After 14 days Red blood cells, 10 ¹² / L 5.4 + 0.38 5.7 ± 0.42 5.5 ± 0.44 5.4 ± 0.51 White blood cells, 10 ⁹ / L 7.0 + 0.41 7.5 ± 0.83 6.8 ± 0.67 5.9 ± 0.23 * Hemoglobin, g / l 127.7 ± 1.26 131.9 ± 9.11 129.9 ± 2.65 114.9 ± 8.84 ESR, mm / hour 3.00 ± 0.16 3.00 ± 0.58 2.67 ± 0.33 1.97 ± 0.33 * Neutrophils,% 3.3 ± 0.88 3.0 ± 0.50 3.2 ± 0.33 3.7 ± 0.58 Segmented 24.6 ± 0.88 24.6 ± 1.20 27.3 ± 6.17 27.1 ± 1.04 Eosinophils,% 1.7 ± 0.12 2.0 ± 0.33 3.0 ± 1.04 2.7 ± 0.67 Basophils,% - - - - Lymphocytes,% 68.8 ± 1.18 68.9 + 1.45 65.4 ± 9.54 65.7 ± 1.67 Monocytes,% 1.57 ± 0.33 1.48 ± 0.41 1.43 ± 0.63 0.67 ± 0.13 * In 21 days Red blood cells, 10 ¹² / L 5.1 ± 0.19 5.3 ± 0.27 5.0 ± 0.36 5.0 ± 0.43 White blood cells, 10 / L 7.8 ± 1.02 8.3 ± 0.64 9.9 ± 0.23 6.9 ± 0.67 Hemoglobin, g / l 135.1 ± 7.97 135.3 ± 5.52 131.4 ± 5.17 126.4 ± 8.39 ESR, mm / hour 3.05 ± 0.24 3.00 ± 0.19 2.87 ± 0.35 1.81 ± 0.11 * Neutrophils,% 2.7 ± 0.67 2.4 ± 0.35 2.3 ± 0.43 5.3 ± 0.38 * Segmented 22.6 ± 3.33 22.7 ± 1.74 24.6 ± 4.67 30.1 ± 4.03 * Eosinophils,% 1.6 ± 0.17 2.0 ± 0.09 2.0 ± 0.24 4.0 ± 1.03 * Basophils,% - - - - Lymphocytes,% 71.7 ± 1.76 72.0 ± 2.71 69.9 ± 4.81 60.1 ± 3.06 * Monocytes,% 1.33 ± 0.27 1.33 ± 0.33 1.27 ± 0.21 0.56 ± 0.12 * * - P <0.05-0.001 compared with control

When examining the blood of animals that were injected with the drug for the treatment of colibacteriosis in young farm animals at doses of 0.16 and 0.40 ml / kg body weight, there were no significant changes in the morphological composition of the blood, and biochemical parameters compared with indicators in the blood of animals of the control groups (tables 12, 13 and 14).

Table 12 Biochemical blood parameters of white rats with repeated intramuscular administration of a drug for the treatment of colibacteriosis in young farm animals Indicators The control Doses of the drug, ml / kg 0.16 0.40 0.80 After 14 days Total protein, g / l 66.7 ± 2.29 62.3 ± 3.08 62.5 ± 4.83 58.8 ± 0.73 * Albumin, g / l 37.0 ± 1.39 40.4 ± 3.58 37.9 ± 1.53 36.1 ± 4.11 Urea, mmol / l 3.77 ± 0.34 3.12 ± 1.09 3.36 ± 0.40 4.99 ± 0.39 * Glucose, mmol / l 7.01 ± 0.79 6.54 ± 0.43 6.71 ± 0.91 7.23 ± 0.15 Cholesterol, mmol / l 1.45 ± 0.21 1.27 ± 0.12 1.16 ± 0.06 1,50 ± 0,37 AsAT, Unit / L 82.6 ± 0.62 83.8 ± 8.97 79.4 ± 3.27 104.6 ± 9.11 * AlAT, Unit / L 56.5 ± 4.26 61.1 ± 6.71 67.2 ± 2.68 93.9 ± 8.17 * Creatinine, μmol / L 63.0 ± 2.92 68.4 ± 4.65 72.5 ± 5.79 86.5 ± 4.65 * Alkaline phosphatase, units / l 133.0 ± 9.9 146.4 ± 10.2 111.1 ± 8.03 124.2 ± 9.24 Bilirubin, μmol / L 4.23 ± 0.29 3.45 ± 0.86 4.32 ± 0.51 5.09 ± 0.34 β-lipoproteins, g / l 5.12 ± 0.14 4.99 ± 0.12 4.87 ± 0.16 5.15 ± 0.58 In 21 days Total protein, g / l 66.5 ± 2.87 63.7 ± 0.67 67.8 ± 4.94 56.0 ± 1.07 * Albumin, g / l 35.9 ± 1.16 38.1 ± 1.64 39.0 ± 0.53 39.9 ± 1.79 Urea, mmol / l 4.09 ± 0.23 4.92 ± 0.73 4.74 ± 0.68 5.87 ± 0.21 * Glucose, mmol / l 5.79 ± 0.30 4.79 ± 0.48 4.37 ± 0.23 5.39 ± 0.62 Cholesterol, mmol / l 0.84 ± 0.18 0.78 ± 0.03 0.90 ± 0.14 1.00 ± 0.17 AsAT, Unit / L 116.8 ± 11.8 106.2 ± 6.85 100.9 ± 5.18 150.2 ± 3.43 * AlAT, Unit / L 63.7 ± 11.3 72.4 ± 11.4 70.8 ± 9.11 105.0 ± 12.7 * Creatinine, μmol / L 61.8 ± 4.19 64.2 ± 2.42 b7.8 ± 5.62 81.0 ± 0.79 * Alkaline phosphatase, units / l 85.1 ± 15.6 75.4 ± 14.6 81.3 ± 7.40 80.7 ± 7.91 Bilirubin, μmol / L 4.66 ± 0.15 3.11 ± 0.52 3.63 ± 0.47 5.18 ± 0.24 β-lipoproteins, g / l 5.07 ± 0.18 5.31 ± 0.27 5.24 ± 0.21 6.48 ± 0.54 * * - P <0.05-0.001 compared with control

The most characteristic change in the blood composition of rats, which was administered a drug for the treatment of colibacteriosis in young farm animals at a dose of 0.80 ml / kg, was a distinct monocytopenia detected on days 14 and 21 of the experiment. In experimental rats, after a 21-day administration of the drug for the treatment of colibacteriosis in young farm animals at the highest dose (0.80 ml / kg), an insignificant but significantly significant decrease in the number of leukocytes, ESR, lymphocytes, as well as an increase in the number of stab and segmented leukocytes, was revealed. eosinophils. It should be noted that 10 days after the last injection of the drug, these indicators in experimental animals were restored to physiological values.

With an increase in the dose of the drug for the treatment of colibacteriosis in young farm animals (0.80 ml / kg), there was a steady tendency to more intense functioning of the excretory system and liver. When the drug was administered intramuscularly at a dose of 0.80 ml / kg body weight for 21 days, the rats of the experimental group significantly increased their serum creatinine content - by 31.1%, urea - by 43.5%, the activity of AlAT, AsAT - by 64 , 8 and 28.6%, respectively, and the level of bilirubin by 27.8%. 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.

The study of the cumulative ability of the drug according to the Lima method showed that fractional administration of the drug to white rats in increasing doses in the first four periods did not affect the increase in body weight of animals compared to the control group. By the beginning of the 6th period (0.75 LD ₅₀ ), a decrease in the growth rate of animals was noted, which continued until the end of the experiment. The total dose at which the beginning of the death of animals was noted was 55.63 ml / kg body weight. With further administration of the drug, the death of white rats lasted up to 26 days from the start of the experiment. On day 28, 40% death of experimental animals was noted. During the experiment, 40% of the animals died (by the end of the experiment, 6 out of 10 animals remained alive). 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 at doses of 0.1 and 0.5 ml / kg body weight for 14 days with an interval between injections of 12 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.

Table 13 Blood counts of clinically healthy piglets with intramuscular use of the drug Indicators Background Doses, ml / kg The control 0.1 0.5 Red blood cells, 10 ¹² / L 5.9 ± 0.21 6.0 ± 0.30 5.9 ± 0.55 6.2 ± 0.32 White blood cells, 10 ⁹ / L 8.9 ± 1.04 9.2 ± 0.19 9.0 ± 0.87 9.6 ± 1.31 Hemoglobin, g / l 107.9 ± 9.1 112.1 ± 4.2 112.9 ± 8.3 106.7 ± 4.5 Total protein, g / l 63.6 + 3.19 65.1 ± 2.73 65.9 ± 6.27 61.2 ± 4.26 Urea, mmol / l 3.88 ± 0, b8 4.03 ± 0.70 4.00 ± 0.56 4.57 ± 0.64 * Glucose, mmol / l 4.67 ± 0.23 4.95 ± 0.39 4.87 ± 0.17 4.91 ± 0.45 Total lipids, g / l 4.14 ± 0.59 4.07 ± 0.64 4.22 ± 0.43 4.11 ± 0.23 AsAT, Unit / L 49.1 ± 6.17 46.9 ± 4.38 47.6 ± 7.02 51.4 ± 3.49 AlAT, Unit / L 34.8 ± 4.18 39.3 ± 2.29 33.5 ± 3.76 38.7 ± 4.19 Creatinine, μmol / L 81.9 ± 9.13 77.8 ± 10.1 80.1 ± 6.26 91.9 ± 3.88 * Bilirubin, μmol / L 1.42 ± 0.04 1.57 ± 0.11 1.49 ± 0.10 1.78 ± 0.26 Neutrophils,% 3.0 ± 0.24 2.9 ± 0.36 3.0 ± 0.35 3.1 ± 0.30 Segmented 37.6 ± 4.51 36.5 ± 3.67 36.1 ± 5.62 37.0 ± 4.22 Eosinophils,% 1.3 ± 0.11 1.2 ± 0.31 1.3 ± 0.28 1.5 ± 0.40 Basophils,% 0.2 ± 0.06 0.2 ± 0.05 0.1 ± 0.05 - Monocytes,% 3.6 ± 1.00 3.7 ± 0.13 3.6 ± 0.44 3.8 ± 1.00 Lymphocytes,% 54.3 ± 7.19 55.5 ± 6.29 55.9 ± 4.17 54.6 ± 4.77 * - P <0.05-0.001

Table 14 Blood counts of clinically healthy calves with intramuscular use of the drug Indicators Background The control Doses, ml / kg 0.1 0.5 Red blood cells, 10 ¹² / L 6.5 ± 0.44 6.4 ± 0.31 6.6 ± 0.16 6.1 ± 0.52 White blood cells, 10 ⁹ / L 10.6 ± 3.97 11.1 ± 5.01 10.8 ± 4.13 11.0 ± 4.56 Hemoglobin, g / l 104.8 ± 9.16 103.1 ± 7.12 110.0 ± 6.04 101.1 ± 9.17 Hematocrit% 36.0 ± 3.15 36.2 ± 0.99 37.1 ± 2.27 36.0 ± 5.07 Total protein, g / l 64.6 ± 2.17 65.0 ± 0.08 66.7 ± 1.54 63.1 ± 3.32 Albumin, g / l 33.8 ± 4.32 34.1 ± 5.17 33.9 ± 6.27 33.1 ± 2.98 Globulins,% α 10.1 ± 2.19 9.8 ± 1.08 10.0 ± 2.31 9.7 ± 1.83 β 11.1 ± 3.07 11.0 ± 2.15 10.8 ± 1.06 10.5 ± 2.11 γ 9.2 ± 1.45 9.1 ± 3.31 9.1 ± 2.64 9.3 ± 1.03 Phosphorus inorgan., Mm / l 1.56 ± 0.13 1.47 ± 0.43 2.06 ± 0.19 1.68 ± 0.26 Urea, mmol / l 4.15 ± 0.24 4.27 ± 0.11 4.99 ± 0.57 5.44 ± 0.36 * Glucose, mmol / l 4.11 ± 0.12 4.03 ± 0.09 3.67 ± 0.21 4.22 ± 0.11 Total lipids, g / l 2.31 ± 0.48 2.16 ± 0.17 1.87 ± 0.08 1.93 ± 0.16 Cholesterol, mmol / l 1.21 ± 0.19 1.18 ± 0.21 0.99 ± 0.16 1.14 ± 0.12 AsAT, UNIT / l 39.4 ± 3.76 36.1 ± 5.04 40.2 ± 4.09 52.8 ± 4.84 AlAT, ED / l 74.5 ± 3.52 76.1 ± 5.99 79.6 ± 7.81 85.0 ± 6.68 Creatinine, μM / L 101.2 ± 4.87 109.4 ± 5.54 106.6 ± 4.48 130.3 ± 5.86 Bilirubin, μM / L 2.38 ± 0.07 2.42 ± 0.24 2.23 ± 0.09 3.26 ± 0.24 Neutrophils,%
Stab 7.1 ± 1.02 6.8 ± 0.77 7.2 ± 0.92 7.1 ± 1.12 Segmented 28.1 ± 3.01 22.3 ± 2.56 22.6 ± 5.16 23.4 ± 2.87 Eosinophils,% 2.1 ± 0.11 1.9 ± 0.15 2.2 ± 0.21 2.1 ± 0.24 Basophils,% 0.4 ± 0.05 0.4 ± 0.06 0.5 ± 0.10 0.4 ± 0.10 Monocytes,% 1.1 ± 0.20 1.2 ± 0.46 1.3 ± 0.36 1.1 ± 0.16 Lymphocytes,% 61.1 ± 5.86 67.4 ± 9.01 66.2 ± 6.13 65.9 ± 7.81 * - P <0.05 with respect to control

The exception was indicators characterizing the functional state of the liver and kidneys. An increase to the upper limits of the norm in the blood serum of urea, creatinine, as well as a slight increase in the amount of bilirubin and AsAT activity indicate an increased load on these organs.

The results obtained in vitro experiments (table 1) indicate a low sensitivity of gram-negative microorganisms to dioxidine. The minimum inhibitory concentration of which was 25.0-100.0 μg / ml. For Pseudomonas aeruginosa - 200.0 μg / ml. The low activity of dioxidine against gram-negative microorganisms is compensated by the second component of the drug - gentamicin. In our studies, the IPC of gentamicin was in the range of 6.25–25.0 μg / ml, and the antibiotic was most active against museum strains (6.25–12.5 μg / ml).

When studying the antibacterial effect of the combination of gentamicin and dioxidine in vitro, we found that the minimum inhibitory concentration of each of the antibiotics in the presence of the other decreases significantly. For example, in the presence of gentamicin at concentrations of 0.56-0.88 μg / ml, the MPC of dioxidine for Escherichia coli 04 decreases to 0.13 μg / ml (190 times). Conversely, the presence in the combination of dioxidine in concentrations of 0.06-0.38 μg / ml reduces the MIC of gentamicin to 0.5 μg / ml (25 times).

When gentamicin is added to dioxidine at a concentration of 2.0 μg / ml, the BMD of the former in relation to Pseudomonas aeruginosa decreases to 10.0 μg / ml (20 times). At the same time, the presence of dioxidine at a concentration of 0.5 μg / ml in relation to this microorganism reduces the MIC of gentamicin to 40.0 μg / ml (1.3 times).

The validity of this combination is due to the fact that two bactericidal agents are simultaneously combined in the dosage form. This provides a synergistic effect due to the fact that both components act in the same phase of cell growth, but on different metabolic pathways.

Dioxidine is active against gram-negative and gram-positive pathogenic and conditionally pathogenic aerobic and anaerobic microorganisms. The antibacterial action of dioxidine is based on the selective suppression of DNA synthesis. In addition, the drug reduces the activity of extracellular nuclease and plasmocoagulase in microorganisms, which leads to dysfunction of the genetic apparatus of the microbial cell and, as a result, the biosynthesis of biologically active macromolecules, which are pathogenicity factors, is suppressed.

Gentamicin acts on many aerobic gram-negative microorganisms and on a part of gram-positive, incl. staphylococci, Escherichia, Pseudomonas aeruginosa, clostridia, proteus. The mechanism of action of gentamicin is associated with a violation of the synthesis of microbial cell polypeptides in ribosomes, thereby disrupting the synthesis of microbial membranes, which leads to the death of bacterial cells.

Thus, the established mutually reinforcing effect of the combination of gentamicin and dioxidine in relation to the studied microorganisms etiologically significant in the development of colibacteriosis, as well as the expansion of the spectrum of antibacterial activity with their combined use, allowed these active substances to be included in the complex preparation.

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

Claims (1)

A preparation for the treatment of colibacteriosis in young farm animals, containing dioxidin, characterized in that it additionally contains gentamicin sulfate, disodium ethylenediamine-N, N, N ', N'-tetraacetic acid 2-aqueous, water for injection in the following ratio of components, wt .%:
Gentamicin sulfate 3.5-4.5 Dioxidine 0.5-1.5 Sodium disodium ethylenediamine-N, N, N ', N' -tetraacetic acid 2-aqueous 0.01 Water for injections up to 100%