EA028412B1 - Pharmaceutical preparation for veterinary purpose - Google Patents

Abstract

A pharmaceutical preparation for veterinary purpose containing an acid from the group of oxy acids and a compound of formula 1where T is a compound of formula 2wherein A is an antibiotic from the group: A1 is a 4-quinolone derivative, compounds containing a fluorine atom at position 6 and at position 7 - the piperazine ring with or without additional substitutions; A2 are substances of a glycosidic nature, the aglycons of which are cyclohexane derivatives containing hydroxyl, amine or guanidine groups; A3 are antibiotics-pyrazonides (lincosamides); A4 is a substance belonging to the class of polyketides with polyfunctional octahydro-tetracene 2-carboxyamide compound; A5 is a substance belonging to the class of polyketides, the basis of the chemical structure of which is a macrocyclic 14- or 16-membered lactone ring to which one or more carbohydrate residues are attached. The result is extension of the range of curable diseases, especially mixed infections, shortening of treatment time, increasing the effectiveness of treatment, and reducing side effects.

Description

The invention relates to inorganic chemicals, in particular to nitrogen compounds, and to substances used in veterinary pharmacology.

Currently, often infectious diseases of animals occur in the form of mixed infections caused by several pathogens. According to researchers, the cause of infectious diseases is often viruses. They play the role of a trigger in the development of the infectious process. Introducing the host organism, viruses weaken the body's resistance and create conditions for the penetration of conditionally pathogenic microflora into the body. Such associated infections require a separate approach to diagnosis and treatment.

In order for the fight against viral and combined infections to be successful, it should be pursued in several directions at once, among which we can single out the effect on the viral pathogen with an antiviral drug, elimination of secondary bacterial infections with an antibacterial component, immunity correction with an immunostimulating drug, attenuation of the manifestations of the disease - symptomatic therapy, restoration of protective barriers of the mucous membranes, as well as the replacement of disturbed physiological functions of the body - substitute effective therapy and detoxification.

With this scheme, as a rule, treatment takes two or more weeks and requires the appointment of a large number of known drugs.

Until recently, there were almost no drugs in the arsenal of veterinarians that directly had antiviral activity, with the exception of serums and immunoglobulins.

The known use of sera and immunoglobulins is most effective only in the initial stage of the disease, often before the onset of clinical signs. At later stages of the disease, the result of their use is less pronounced, and the treatment of combined infections actually comes down to the fight against the symptomatic manifestations of such infections.

Known veterinary implantable immunostimulating drug containing melatonin, biodegradable polymer base - cyacrine-EO and plasticizer, characterized in that it additionally contains xymedon in the following ratio, wt.%:

melatonin 5-25, xymedon 5-25, cyacrine-EO (polymer) 89.95-35, plasticizer 0.05-15.

As a biodegradable polymer, it contains water-soluble cellulose derivatives and processing aids in the following ratio of components, wt.%:

melatonin 10-50, cellulose derivatives 89.95-35, technological additives 0.05-15.

As processing aids, it contains water-soluble cellulose derivatives, preferably methyl cellulose, sodium carboxymethyl cellulose.

The drug in special cases additionally contains xymedon in the following ratio of components, wt.%:

melatonin 5-25, xymedon 5-25, cellulose derivatives 89.95-35, technological additives 0.05-15 (KI 2219910).

The disadvantages of this well-known drug are the complexity of use, the narrowness of the range of diseases that can be effectively treated, a large amount of contraindications and side effects.

Also known is a preparation that is a composition with anti-infective activity, made in solid dosage form for oral administration in the form of a powder, which is a balanced complex comprising a probiotic agent, an adsorbent and an auxiliary additive, in which sterilized culture fluid containing metabolites is used as a probiotic agent strain VKPM No. В-2335 of the bacteria Bacillus bisphiu1b1, zeolite as an adsorbent, and calcium stearate as an auxiliary additive I or aerosil, characterized in that it further comprises a highly immunomodulatory agent, representing a complex of polysaccharides - the products of enzymatic hydrolysis of polymers of the inner and outer layers of the cell envelope of brewer's yeast, as a β-glucan and mannan (CI № 2,476,205).

The disadvantages of this well-known drug are the narrowness of the range of infections that can be effectively cured, the complexity of use, a large amount of contraindications and side effects.

Known drug veterinary use, which is a composition for the treatment of microbial and parasitic infections in animals, comprising a compound of the following formula:

in which K means CHC _{1 2} , X - 8O ₂ CH ₃ ; X 'is hydrogen, Ζ is hydrogen, ivermectin and at least one carrier (KI 2359667, prototype).

The disadvantages of the known drug are the narrowness of the range of application (functionality), the duration and complexity of use, a large amount of contraindications and side effects.

An object of the invention is the creation of an effective drug for veterinary use, with activity in mixed infections and the expansion of the arsenal of such drugs.

The technical result that provides the solution of the problem lies in expanding the range of treatable diseases, especially mixed infections caused by several pathogens of various etiologies (viral and bacterial), reducing treatment time, increasing the effectiveness of treatment, i.e. the number of cured animals, and the absence of relapse, as well as reducing side effects during treatment, increasing the economic efficiency of animal husbandry.

As you know, antibiotic therapy has a strong side effect on the microflora of the patient and leads to its violation. Violation of microcenosis can lead to symptoms of indigestion and decreased productivity.

When using the claimed preparation by reducing the treatment time and, accordingly, the duration of antibiotic administration, the negative effect of antibiotic components on the microcenosis of animal patients is reduced and, as a result, the above side effects are reduced during therapy. In agriculture, the incidence and mortality of animals has a direct impact on the decline in economic indicators and leads to losses, both due to the departure of animals, and due to lost profits with a decrease in productivity during illness. Thus, an increase in the percentage of recovered animals and a decrease in the duration of the disease, along with a reduction in the duration of treatment, when using the composition can improve the economic indicators of animal husbandry.

The inventive preparation has enhanced functionality and is configured to treat young cattle, pigs, sheep and goats, dogs and cats with viral, bacterial and infections of mixed etiology, digestive, genitourinary, septicemia and other diseases caused by viruses sensitive to the ingredients of the composition and bacteria. The drug is made with the possibility of treating the following diseases of domestic animals, among others: in cats - panleukopenia, viral rhinotracheitis, calcivirosis, in dogs - corona and parvovirus enteritis, adenovirus, infectious laryngotracheitis (nursing cough), and plague. The drug is made with the possibility of treatment, including the following diseases of farm animals: viral diarrhea, rotavirus, coronavirus infection, transmissible pig gastroenteritis virus, enterovirus infection, reproductive and respiratory syndrome. The drug is made with the possibility of treating domestic and farm animals with viral infections complicated by bacterial ones - colibacteriosis, protea infection, salmonellosis, pasteurellosis, actinobacillosis, hemophilosis, etc., as well as with separately occurring bacterial infections.

Contained in the proposed drug acid from the group of hydroxy acids (acid containing a carboxyl and hydroxyl group) provides the claimed preparation in the process of hydrolysis at elevated temperatures. Hydroxy acids (hydroxycarboxylic acids, hydroxycarboxylic acids, fruit acids) - carboxylic acids, which simultaneously contain carboxyl and hydroxyl groups, for example, fruit acids: tartaric acid, citric acid, malic acid, etc. lactic acid; tartaric acid and others. Hydroxy acids exhibit all the properties characteristic of acids (dissociation, the formation of salts, esters, etc.), and the properties characteristic of alcohols (oxidation, the formation of ethers, etc.). In addition to the technological properties, upon receipt of the inventive preparation, an acid from the group of hydroxy acids can also be a physiological metabolite and used by the body to generate energy, especially intensively under conditions of hypoxia. In this case, acid molecules from the group of hydroxy acids do not require transport systems inside cells, unlike glucose, which requires insulin to transport, and as a result, they can be used most intensively by the cells of the heart muscle and brain cells (neurons). In the proposed preparation, the value of an acid from the group of hydroxy acids is realized as a therapeutic agent - an energy source for the body in case of illness.

The essence of the invention lies in the fact that the pharmaceutical preparation of veterinary use contains an acid from the group of hydroxy acids (an acid containing a carboxyl and hydroxyl group) or carboxylic acids (formic or other acid containing a carboxyl group) and a compound of formula 1

- 2 028412

where T is 1 - [(2K, 3K, 48.5K) -3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-yl] -1H1,2,4-triazole-3-carboxamide (C ₈ H ₁₂ K ₄ O ₅ ), i.e. compound of formula (2)

wherein

A is an antibiotic from the group:

A1 is a derivative of 4-quinolone, compounds containing a fluorine atom at position 6, and at position 7

- piperazine ring with or without additional substitutions;

A2 - substances of a glycosidic nature, the aglycones of which are cyclohexane derivatives containing hydroxyl, amino or guanidine groups;

A3 - antibiotics - pyrazonides (lincosamides);

A4 - a substance belonging to the class of polyketides with polyfunctional octahydrotetracene

- 2-carboxyamide compound;

A5 - a substance belonging to the class of polyketides, the basis of the chemical structure of which is a macrocyclic 14- or 16-membered lactone ring, to which one or more carbohydrate residues are attached.

In particular cases of implementation, antibiotic A1 is a 4-quinolone derivative, compounds containing a fluorine atom at position 6, and a piperazine ring with or without additional substitutions at position 7, is an antibiotic from the group with general formula 3

Including

A1-1 - 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (4-ethyl-1-piperazinyl) -3-quinolinecarboxylic acid (enrofloxacin) ^ ₉ Η ₂₂ ΕΝ ₃ Ο ₃ having the following structural formula (hereinafter, after the name of the antibiotic, its structural formula is given)

A1-2 - 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-quinoline-3-carboxylic acid (ciprofloxacin) ^ ₇ Η _ί8 ΕΝ ₃ Ο ₃

A1-3 - 1-ethyl-6-fluoro-7- (4-methyl-1-piperazinyl) -4-oxo-3-quinolinecarboxylic acid (as mesylate) (pefloxacin) ^ ₇ Η ₂₀ ΕΝ ₃ Ο ₃

A1-4 - 9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-7H-pyridol (3.2.1y) (4.2.1 ) benzoxidiazine-6 carboxylic acid (marbofloxacin).

- 3 028412

Equivalent: 9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-7H-pyridol (3.2.1 y) (4.2.1) benzoxidiazine-6 carboxylic acid С ₁₇ Н ₁₉ РЫ ₄ О ₄

In other special cases, the implementation of the antibiotic A2 is a substance of a glycosidic nature, the aglycones of which are derivatives of cyclohexane containing hydroxyl, amino or guanidine groups, in particular

A2-1 - [2K- (2a, 4av, 5av, 6v, 7v, 8v, 9a, 9a, 10av)] - decahydro-4a, 7,9-trihydroxy-2-methyl-6,8-bis- ( methylamino) -4H-pyrano [2,3, b] [1,4] benzodioxin-4-one (and in the form of dihydrochloride) (spectinomycin) ^ ₄ Η ₂₄ Ν ₂ Ο ₇

A2-2 - (3K, 4K, 5K) -2 - {[(18.28.3K, 48.6K) -4,6-diamino-3 - {[(2K, 3K, 68) -3-amino 6 - [(1K) -1- (methylamino) ethyl] oxan-2-yl] oxy} -2-hydroxyl cyclohexyl] oxy} -5-methyl-4- (methylamino) oxan-3,5-diol (gentamicin) .

Equivalent: (3K, 4K, 5K) -2 - {[(18.28.3K, 48.6K) -4,6-diamino-3 - {[(2K, 3K, 68) -3-amino-6- [(1K) -1 (methylamino) ethyl] oxan-2-yl] oxy} -2-hydroxyl cyclohexyl] oxy} -5-methyl-4- (methylamino) oxane-3,5 diol ^ ιΗ ₄₃ Ν ₅ Ο ₇ he but

LY, ^ΝΗί

In other special cases, the implementation of the antibiotic - pyrazonide (linkosamide) A3 is an antibiotic from the group:

A3-1 - (28-trans) -methyl-6,8-dideoxy-6 - [[(1-methyl-4-propyl-2-pyrrolidinyl) carbonyl] amino] -1TA --------- --TA ------------------------- Ζ --------------------- , --------- X Ζ ------------------ X ^ 34 ^ 068

A3-2 - and its semisynthetic derivative (28.4K) ^ - {2-chloro-1 - [(2K, 3K, 48.5K, 6K) -3,4,5trihydroxy-6- (methylsulfanyl) oxan-2- sludge] propyl} -1-methyl-4-propylpyrrolidine-2-carboxamide (clindamycin) Cx ₈ H ₃₃ N ₂ O ₅ 8

In other special cases, the implementation of the antibiotic A4 is a substance belonging to the class of polyketides with a polyfunctional octahydrotetracene 2-carboxyamide compound, in particular, is an antibiotic from the group:

A4-1 - [48- (4a, 4aa, 5a, 5aa, 6a, 12aa)] - 4- (dimethylamino) -1,4,4a, 5,5a, 6,11,12a-octahydro-3,5, 10,12,12 pentahydroxy-6-methyl-1,11-dioxo-2-naphthacene carboxamide (as hydrochloride, monohydrate or cyclate) (doxycycline) C ₂₂ H ₂₄ ^ O ₈

A4-2 - (48.4aK, 58.5aK, 68.12a8) -4- (dimethylamino) -3,5,6,10,11,12a-hexahydros-6-methyl-1,12 dioxo-1,4, 4a, 5.5a, 6,12,12a-octahydrotetracin-2-carboxamide (oxytetracycline) C ₂₂ H ₂₄ ^ O ₉

- 4,084,412

In other special cases, the implementation of the antibiotic A5 is a substance belonging to the class of polyketides, the basis of the chemical structure of which is a macrocyclic 14- or 16-membered lactone ring, to which one or more carbohydrate residues are attached, in particular, is an antibiotic from the group:

A5-1 - 20-deox-20- (3,5-dimethylpiperidin-1-yl) desmicosin phosphate (tilmicosin)

S4bN _{8 (} No. O1z-NzRO4

A5-2 - (3K, 48.58.6K, 7K, 9K, 11K, 12K, 138.14K) -4 - [(2,6-dideoxy-3-C-methyl-3-O-methyl-a- B-ribohexopyranosyl) oxy] -7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-10 - [(E) - [(2-methoxyethoxy) methoxy] imino] -6- [ (3,4,6-tridesoxy-3-dimethylamino-b-E-acid-hexopyranosyl) -oxy] -14-ethylloxycyclotetradecan-2-one (roxithromycin) C ₄₁ H ₇ ^ ₂ O ₁₅

In any of these particular cases of implementation, the preparation can be performed using one of the hydroxy acids, in particular, made in the form of a solution in water for oral administration or for injection, preferably in the form of a steam sterilized aqueous solution for injection with a steam injection for 45 min at a temperature of 100 ° С pH 3-5.5, and filtered sequentially through filters with a filter fineness of 0.45 and 0.22 microns.

The drug is preferably administered subcutaneously or intramuscularly once a day for 3 days, in the following doses:

calves, lambs, kids, dogs and cats - subcutaneously in a dose of 1 ml per 10 kg of animal weight; piglets - intramuscularly at a dose of 1.5 ml per 10 kg of animal weight.

In any of the aforementioned particular cases of implementation, the preparation can be made in the form of a powder for oral administration by drying in a spray dryer (without a sterilization step).

The achievement of a technical result as a result of the use of the drug is confirmed by field studies below.

Examples of the use of the drug, confirming the receipt of a technical result.

1. Report on the use of the claimed drug for mixed infections of calves.

The aim of the study was to study the effectiveness of the claimed drug for the treatment of infectious diseases of young farm animals of viral and bacterial etiology.

Research Methodology.

The study was conducted on calves with viral and bacterial gastrointestinal diseases, in particular, with the isolation of the virus of coronavirus infection, as well as a bacterial pathogen (colibacteriosis). For the study, two groups of calves up to 10 days old were formed.

When the disease occurred, the claimed preparation was used with the clindamycin antibiotic at a dose of 1 ml per 10 kg of animal weight once a day for three consecutive days.

In case of a disease, the calves of the control group used an injection solution containing the spectinomycin antibiotic in the form of a 10% solution in a dose of 1 ml per 10 kg of animal weight 1 time per day for 5 days and an interferon preparation in the recommended dosage.

- 5,084,412

The calves were clinically monitored, control weighing was carried out, incidence and mortality were recorded.

Research results.

Table 1

The results of the use of the drug with the antibiotic clindamycin

No. Index Experienced group Control Group one Number of goals 24 twenty 7 Fallen, goals one 3 10 Preservation,% 95.8 85 eleven The average duration of the disease, days 2,4 4.0

Thus, the use of the claimed drug for associated viral and bacterial infections of the gastrointestinal tract in calves helps to increase the safety and reduce the duration of treatment compared with the control.

2. Report on the use of the claimed drug for mixed infections of piglets.

The aim of the study was to study the effectiveness of the claimed drug for the treatment of infectious diseases of young farm animals of viral and bacterial etiology.

Research Methodology.

The study was conducted on a farm unsuccessful for viral and bacterial respiratory diseases and gastroenteritis in piglets. Pathogens of viral diseases: rotavirus, coronavirus, enterovirus infections were isolated in pigs on the farm. These diseases often occur in the form of associations. Thus, pig rotavirus disease (PBC) in combination with porcine transmissible gastroenteritis (TBC) is found in 51% of cases, PBC + TGS + enterovirus infection of pigs (EVBS) - in 20% of cases, RVBS + EVIS - in 29% of cases. Pig reproductive and respiratory syndrome, complicated by pasteurellosis, actinobacillosis, hemophiliasis and other bacterial infections, is often found in piglets of the growing group. For the study, two groups of piglets of growing age 30-35 days were formed.

When the disease occurred to the piglets of the experimental group, the claimed preparation was used with the antibiotic enrofloxacin at a dose of 1 ml per 10 kg of animal weight once a day for three consecutive days. In case of a disease, pigs of the control group used enrofloxacin and trimethoprim in similar doses once a day for 5 days, as well as an interferon preparation. The pigs were clinically monitored, control weighing was carried out, incidence, mortality and unproductive retirement were recorded.

Research results.

table 2

The results of the use of the claimed drug with the antibiotic enrofloxacin.

No. Index Experienced group Control group one Number of goals 561 560 2 Live weight when staged, 5230 5346 3 Live weight per 1 goal., Kg 9.3 9.5 4 Amount at the end of the experiment, goals 521 453 5 Live weight at the end of the experiment, kg 7971 8488 6 The average daily gain, g 300 280 7 Fallen, goals sixteen 36 8 Forced killed, goals 24 71 nine Unproductive retirement, goals 40 107 10 Preservation,% 92.9 81 eleven Incidence,% 48 54 - gastroenteritis, goals 179 198 - bronchopneumonia, goals 92 108

Thus, the use of the preparation according to example 1 for associated viral and bacterial infections of the gastrointestinal and respiratory tract in piglets of the growing group helps to increase safety, average daily growth and shorten the treatment period compared to the control.

3. Report on the use of the claimed drug for mixed infections of chickens.

The aim of the study was to study the effectiveness of the claimed drug for the treatment of infectious diseases of chickens of viral and bacterial etiology.

Research Methodology.

The study was conducted on chickens with mixed pathology of the respiratory tract (mycoplasma infection complicated by colibacteriosis and viral infection).

For the study, two groups of chickens were formed.

When a disease occurred, the claimed preparation with

- 6,028,412 with the antibiotic ciprofloxacin in a dose of 100 ml per 100 l of water for drinking for three consecutive days.

When a disease occurred, ciprofloxacin in the form of a 10% oral solution, trimethoprim in a similar dosage in the form of an oral solution with water for drinking for 5 days, and interferon preparation in the recommended dosage were used for chickens in the control group. Conservation, weight gain of chickens and feed conversion were taken into account.

Research results.

Table 3

The results of the use of the drug with the antibiotic ciprofloxacin

a drug Group An experience The control Number of goals 4968 5045 Case, goals 229 404 % safety 95.4 91.9 Wed live weight 42 1945 1874 days (g) The average daily gain (g) 45,2 43.5 Feed conversion 1.96 2.03

Thus, the use of the claimed drug for associated viral and bacterial infections of the respiratory tract in chickens helps to increase safety, average daily growth and reduce feed costs compared to control.

4. Report on the use of the claimed drug for mixed infections of chickens.

The aim of the study was to study the effectiveness of the claimed drug for the treatment of infectious diseases of chickens of viral and bacterial etiology.

Research Methodology.

The study was conducted on chickens with mixed pathology of the respiratory tract (mycoplasma infection complicated by colibacteriosis and viral infection). For the study, two groups of chickens were formed. When a disease occurred, the claimed preparation was used with the antibiotic roxithromycin at a dose of 100 ml per 100 l of water for drinking for three consecutive days. When a disease occurred, roxithromycin and trimethoprim were used in the form of a solution for oral administration in a dose of 100 ml per 100 l of water for drinking for 5 days and the preparation of interferon in the recommended dosage. The safety of chickens was taken into account.

Research results.

Table 4

The results of the use of the drug with the antibiotic roxithromycin

Indicators An experience The control Age of chickens, days fifteen fifteen The number of chickens in the group, goals 2800 2800 The number of fallen chickens, goals 35 68 Duration of treatment, days 3 5 The safety of the livestock,% 98.7 97.5

Thus, the use of the claimed drug for associated viral and bacterial infections of the respiratory tract in chickens improves the safety of chickens and shortens the treatment period.

5. A clinical study of the drug in the form of a solution for injection with edematous disease of piglets.

The objective of the study: to study the clinical efficacy of the composition according to example 1 for injection in the treatment of edematous disease of piglets caused by gram-negative bacteria.

1. Materials and methods.

Preparations.

Experience: the claimed drug with the antibiotic enrofloxacin in the form of a solution for injection. Control: 10% solution of florfenicol for injection.

1.2. Animals.

Piglets of 45 days of age mixed breeds, unvaccinated.

Animals were divided into 6 groups.

- 7 028412

Table 5

Groups of animals and dosage regimens.

Group Count in Weight in kg per Start research Dose ml per 10 kg Way destination The control (infected) 10 10.75 ± 1.46 Infection lack of treatment Experience 1 10 10.65 ± 1.33 0.5 intramuscularly Experience 2 10 10.85 ± 1.03 one intramuscularly Experience 3 10 11.05 ± 1.44 2 intramuscularly Positive the control 10 10.55 ± 1.14 2 intramuscularly

1.3. Artificially caused edematous disease of piglets.

1.3.1 The strain of Escherichia coli.

The study used a pathogenic strain of Escherichia coli isolated from the site of infection of the edematous disease. The dried and frozen strain was cultured on a nutrient medium for 18 hours, then injected subcutaneously into mice at a dose of 0.1 ml per animal. The strain of Escherichia coli was isolated from the liver of mice, the content of colonies in 1 ml was calculated, and the inoculum was diluted to a concentration of 0.6 million E-CoN / ml.

1.3.2 Inoculation of pigs was carried out 1 ml of inoculum per head intravenously.

1.3.3 Clinical observation.

Body temperature was measured before and after infection, the state of the animal, feed intake, and the nature of feces were evaluated. Pathological and cultural studies were carried out in the fallen piglets.

Treatment.

After inoculation and the appearance of symptoms of edematous disease: high fever, vomiting, decreased appetite, diarrhea, animals were prescribed treatment based on the group. The drugs, in particular, in experiments 1-3, were administered once a day for three days. The period of observation of animals was 15 days from the start of treatment.

2. Results.

2.1 Control (infected).

out of 10 piglets, they died 1-18 hours after inoculation. The remaining piglet showed clinical signs of edema. Body weight decreased at the end of the study. In dead piglets, an E. coli culture was isolated.

2.2 Experience.

2.2.1 Experience 1.

There was no mortality, in one animal the ataxia disappeared 12 hours after the second injection, in the rest after 1 injection.

2.2.2 Experience 2.

the pig fell 30 hours after completion of therapy. E. coli culture was isolated from mesenteric lymph nodes. In other animals, the clinical signs of the disease disappeared 12 hours after the first injection of the drug.

2.2.3 Experience 3.

the pigs fell on the 2nd and 4th days from the start of treatment, respectively. E. coli culture was isolated from mesenteric lymph nodes. In other piglets, the clinical signs disappeared 12 hours after the 1st injection.

2.4 Positive control.

the pigs fell 2-4 days after the start of treatment. E. coli culture was isolated from the spleen, liver and mesenteric lymph nodes. In 4 piglets, the clinical signs disappeared at the end of treatment; in 3 pigs, the inhibited state persisted until the end of the study.

3. Conclusion.

3.1 Mortality of animals was statistically significantly different in the treatment of edematous disease and in the control group without treatment.

3.2 There were no significant differences in mortality between the experimental groups and the positive control group. However, in the degree of recovery, the experimental groups had significant differences with the positive control group.

Based on the results of the study, the optimal dose of the claimed drug for the treatment of edematous disease of piglets is a dose of 1 ml per 10 kg of body weight.

6. Clinical study of the drug with the antibiotic enrofloxacin for the treatment of calf diarrhea.

1. Materials and methods.

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Tested drugs.

An experience.

The claimed drug and with the antibiotic enrofloxacin.

Dose: 0.1 ml per 10 kg of mass intramuscularly 1 time per day.

Control: enrofloxacin 5% injection for a similar dose.

Animals.

256 calves with symptoms of a disease of the gastrointestinal tract in the form of diarrhea. The main causative agents of calf diarrhea were Escherichia coli, dysentery bacillus, and salmonella.

2. Results.

Table 6

Research results

Group Number, goals Vizdorov- laziness goals Partial get well laziness goals % efficiency Average continue bodyness treatment one 156 123 29th 97.4 2.5 2 one hundred 54 32 86 3.8

3. Conclusion.

Based on the results of the study, we can conclude that the claimed preparation in the form of a solution for injection is effective in the treatment of bacterial-viral diarrhea of calves with a treatment efficiency of 97.4%.

No statistically significant differences between the groups were detected, but during treatment with the claimed composition, the animals recovered 1.3 days earlier compared to the control.

The main causative agents of calf diarrhea were Escherichia coli, dysentery bacillus, and salmonella. The results of the study indicate the effectiveness of the claimed drug against these pathogens.

7. Report on the use of the drug with the antibiotic enrofloxacin in pets.

Introduction

The claimed drug with the antibiotic enrofloxacin was used in the treatment of the following viral and mixed viral and bacterial diseases: viral rhinotracheitis, calicivirus, infectious laryngotracheitis (aviary cough complex), cystitis.

In total, 11 animals were involved in the experiments. Of them:

dogs aged 1-3 years, males; diagnosis - infectious laryngotracheitis;

cats aged 2-5 years; diagnosis of viral rhinotracheitis;

cats aged 1.5-3 years; the diagnosis is calicivirosis;

cats aged 3 and 5 years, males; the diagnosis is cystitis.

The claimed drug and with the antibiotic enrofloxacin was used as part of complex therapy:

dogs at a dose of 0.1 ml / kg 1 time per day subcutaneously for 7 days, were additionally prescribed: 10% butophosphamide solution subcutaneously 1 time per day, inside - bromhexine 3 times a day, cats with GVK1 - at a dose of 0 , 1 ml / kg 1 time per day for 7 days, additionally Vitafel C serum, 1 dose s / c twice with an interval of 24 hours, gamavit, inside - Ascoril 3 times a day, intranasally - drops of Anandine, in the eyes of Tobrex, cats KVK - at a dose of 0.1 ml / kg 1 time per day for 7 days, additionally not vaccinated cats, Vitafel C serum, 1 dose s / c twice with an interval of 24 hours, all animals - gamavit, treatment of the oral cavity with monclavite; cats with high fever, intramuscularly administering diphenhydramine once with intramuscular injection, cats with cystitis - at a dose of 0.1 ml / kg once a day for 7 days to one animal (hereinafter, the owners chose to switch to oral administration of the drugs) and 10 days to the second animal; additionally used no-shpa, etamzilat, Cot Erwin; in one animal, prednisone is doubled. One of the cats was prescribed the drug after the use of enrofloxacin in mono mode gave a very mild clinical effect.

The effectiveness of the drug was taken into account, based on a change in clinical signs and, in the case of cystitis, on changes in the urinary OCA. In dogs, cough episodes became significantly rarer within 2 days, the cough became milder; by the 5th day in one dog the cough occasionally continued and completely stopped by the 7th day.

Cats with GVK 1 - in all animals a significant improvement was noted by the 3rd day, in all animals a complete restoration of appetite, a decrease in the number of outflows from the nasal passages, in 1 animal the signs of blepharitis significantly decreased, in 3 others were expressed; by the 5th day of discharge from the nasal passages were absent in all animals, signs of blepharitis remained poorly expressed in 3 cats - they were prescribed additional treatment; in a cat with bronchitis - there was no wheezing during auscultation, rigid vesicular breathing remained; by day 7 only 2 cats out of 4 retained signs of blepharitis; the cat with bronchitis in the control image was not abnormal.

Cats with CVC - on the second day of treatment, there was no rise in temperature, by day 3 the outflow from the nasal passages stopped, the appetite was completely restored; erosive lesions disappeared by the 7th day of treatment in 2 cats out of 3. Cats with cystitis - in one of the cats by 7 days all signs of cystitis disappeared, urinary OCA showed an insignificant number of leukocytes, squamous epithelium; in the second animal, despite the disappearance of clinical signs, the leukocytes and coccal flora ++ remained in the control urine OKA by day 10.

During treatment, no side effects were observed in any animal. Subcutaneous soreness was noted in 3 out of 9 cats; dogs did not show soreness when injected.

Conclusion

As a result of clinical studies established high therapeutic efficacy of the claimed drug for infectious laryngotracheitis of dogs, viral rhinotracheitis of cats and calicivirus infection in cats.

8. Report on the use of the claimed drug in the treatment of viral whitening in small non-productive animals.

The claimed drug with the antibiotic enrofloxacin was used in dog and cat kennels in the territory of the city of Chelyabinsk from 01.10.2013 to 01.02.2014. In the nursery No. 1 in cats with the disease of viral rhinotracheitis, drug treatment was applied using the claimed drug at a dose of 0.1 ml / kg live weight. The drug was administered subcutaneously once a day. 5% ascorbic acid was also used in the same dose; the course of treatment is planned for three days. The interval between injections was 24 hours. The result of treatment was visible the next day. The condition of the animals improved markedly, there was no fever, eyes were open, lacrimation was not observed. One day after the end of treatment, the animals did not have redness of the upper respiratory tract, eye conjunctiva. The general condition of the animals is satisfactory.

Conclusion

After the treatment, the animals recovered, there were no clinical signs of this disease. The use of the claimed drug showed a good result in the treatment of viral diseases and the absence of complications after the transfer of this disease.

In the cat nursery No. 2, in the treatment of feline viral rhinotracheitis, a similar treatment regimen was used with the claimed drug. Clinical recovery occurred after two to three days of treatment.

The claimed drug is also used in dog kennels in case of viral and mixed infections with positive results.

Conclusion

The claimed drug showed a good result in the treatment of viral and mixed infections. When used with other drugs, no complications or side effects were observed. To date, this drug is one of the most effective treatments for viral and mixed infections.

9. A clinical study of the drug with the antibiotic enrofloxacin for the treatment of calf bronchopneumonia.

Tested drugs.

Experience: the claimed drug with the antibiotic enrofloxacin.

Control: enrofloxacin in a similar dosage.

Materials and methods.

The work was carried out in the conditions of the dairy complex of the pedigree breeding company of Urozhaynoye, Novoaleksandrovsky District, Stavropol Territory, on heifers and gobies of the Yaroslavl Holstein breed, aged 14 days. We performed an analysis of outpatient journals on the incidence and retirement of animals from January to May 2014, conducted biochemical blood tests in experimental animals and in animals of the control group.

When studying an outpatient journal, one can make an analysis that the incidence of calves with bronchopneumonia at a month of age is at a high level, despite the fact that the conditions of detention and feeding comply with generally accepted standards. Also, when studying the documentation, we came to the following conclusion that during the current year, the complex observed the departure of calves from the age of one to three months.

A high percentage of calf retirement is observed in the month of February and amounts to 23.5%, and the number of registered sick calves is 17 goals. Also, a high percentage of calf retirement due to bronchopneumonia is observed in April and January and amounts to 21.4 and 21.7%, respectively.

The objective of our research was to test a method for treating bronchopneumonia in calves using the claimed drug with the antibiotic enrofloxacin, and to determine, in a comparative aspect, therapeutic efficacy with the reference drug, which contains enrofloxacin. Under observation there were two groups of calves of 20 goals each from the age of 14 days to 1 month, the groups were formed on the basis of analogues. The first experimental group included calves with the characteristics of 10,084,412 bronchopneumonia, which were administered the claimed drug, the second control group included calves, which were used according to the instructions and instructions of the drug enrofloxacin. Treatment regimens are presented in table. 2.

Table 7

Clinical trial data

Group Name number animals Goal Single dose drug ml Frequency of use (day) number days Therapeutically and I efficiency % Experienced twenty 5 Once a day 3 90% Control I twenty 5 Once a day 5 65%

In the control group, treatment efficiency was lower, in addition, there was a case of one calf.

Also, according to the conditions of scientific and economic experience, the state of some biochemical blood parameters was evaluated in calves of the control and experimental groups before and after the use of drugs. The data of biochemical blood tests are presented in table. 3.

Table 8

Biochemical parameters in calves before and after treatment, M ± t, n = 20

Index Experienced group Control group Before treatment After treatment Before treatment After treatment Carotene, mg% 0.16 ± 0.03 0.29 ± 0.04 0.14 ± 0.05 0.21 ± 0.04 Total protein, g% 7.23 ± 0.01 6.42 ± 0.02 7.21 ± 0.02 7.03 ± 0.03 Reserve alkalinity, Vol. % CO2 43.6 ± 1.1 53.8 ± 1.01 46.5 ± 0.09 51.3 ± 1.2

When analyzing the results of the table. 8 we can conclude that in all animals there is a decrease in carotene, reserve alkalinity, and an increase in total protein in blood serum is also noted. After the events, in the experimental group there was an increase in carotene by 45% to normal limits, the amount of alkaline reserve increased by 19%, the amount of total protein decreased by 11.3% to the physiological norm. In the control group, it was noted that reserve alkalinity increased by 10%, total protein decreased by 2.5% and approached the extreme limits of the physiological norm.

Conclusion

The claimed drug has a higher therapeutic efficacy in calf bronchopneumonia compared with the control.

The use of the claimed drug is preferred in cases of complicated viral-bacterial infections of various organs and systems of the animal’s body, in particular, but not limited to, the genitourinary system to obtain a pronounced therapeutic result in a short time.

The above experimental results confirm the achievement of the technical result, which consists in expanding the range of treatable diseases, especially mixed infections caused by several pathogens of various etiologies (viral and bacterial), shortening the duration of treatment, increasing the effectiveness of treatment, i.e. the number of cured animals and the absence of relapse, as well as reducing side effects during treatment, increasing the economic efficiency of animal husbandry.

Claims (13)

CLAIM 1. Pharmaceutical preparation of veterinary use containing an acid from the group of hydroxy- - 11,084,412 where T is a compound of formula 2 1 - [(2K, 3K, 48.5K) -3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-yl] -1H-1,2,4-triazole-3-carboxamide, wherein A is an antibiotic from any group A1-A5: A1 is a 4-quinolone derivative, compounds containing a fluorine atom at position 6, and at position 7, a piperazine ring with or without additional substitutions, which are an antibiotic from the group: enrofloxacin, ciprofloxacin, pefloxacin, marbofloxacin; A2 - substances of a glycosidic nature, the aglycones of which are cyclohexane derivatives containing hydroxyl, amino or guanidine groups, which are antibiotics from the group: spectinomycin, gentamicin; A3 - an antibiotic from the group: lincomycin, clindamycin; A4 - a substance belonging to the class of polyketides with a polyfunctional octahydrotetracycene 2-carboxyamide compound, which is an antibiotic from the group: doxycycline, oxytetracycline; A5 - a substance belonging to the class of polyketides, the basis of the chemical structure of which is a macrocyclic 14- or 16-membered lactone ring, to which one or more carbohydrate residues are attached, and which are antibiotics from the group: tilmicosin, roxithromycin. 2. The drug according to claim 1, characterized in that the antibiotic A1 is a 4-quinolone derivative, compounds containing a fluorine atom at position 6, and a piperazine ring with or without additional substitutions at position 7, is an antibiotic with the general formula 3 selected from the group A1-1- A1-4, where A1-1 - 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (4-ethyl-1-piperazinyl) -3-quinolinecarboxylic acid (enrofloxacin) 9ι ₉ Η ₂₂ ΡΝ ₃ Θ ₃ , having the following structural formula (hereinafter, after the name of the antibiotic, its structural formula is given) A1-2 - 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-quinoline-3-carboxylic acid (ciprofloxacin) ϋι ₇ 8ι ₈ ΕΝ ₃ Θ ₃ A1-3 - 1-ethyl-6-fluoro-7- (4-methyl-1-piperazinyl) -4-oxo-3-quinolinecarboxylic acid (as mesylate) (pefloxacin) ϋι ₇ Η ₂₀ ΕΝ ₃ Θ ₃ A1-4 - 9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-7H-pyridol (3.2.1 q) (4.2, 1) benzoxidiazine-6 carboxylic acid (marbofloxacin) C ₁₇ H ₁₉ P ^ O ₄ . 3. The drug according to claim 1, characterized in that the antibiotic A2 is a substance of a glycosidic nature, the aglycones of which are cyclohexane derivatives containing hydroxyl, - 12,084,412 amino or guanidine groups, in particular A2-1 - A2-2, where A2-1 - [2K] - (2a, 4av, 5av, 6v, 7v, 8v, 9a, 9aa, 10av)] - decahydro-4a, 7,9-trihydroxy-2-methyl-6,8-bis (methylamino ) -4H-pyrano [2,3, b] [1,4] benzodioxin-4-one (and in the form of dihydrochloride) (spectinomycin) 6χ4 ^Η 24 ^Ν 2 ^Ο 7 A2-2 - (3K, 4K, 5K) -2 - {[(18.28.3K, 48.6K) -4,6-diamino-3 - {[(2K, 3K, 68) -3-amino 6 - [(1K) -1- (methylamino) ethyl] oxan-2-yl] oxy} -2-hydroxycyclohexyl] oxy} -5-methyl-4- (methylamino) oxan-3,5-diol (gentamicin) 0 ₂ ιΗ ₄₃ Ν ₅ 0 ₇ 4. The drug according to claim 1, characterized in that the antibiotic - pyrazonide (linkozamide) A3 is an antibiotic from the group A3-1 - A3-2, where A3-1 - (28-trans) -methyl-6,8-dideoxy-6 - [[(1-methyl-4-propyl-2-pyrrolidinyl) carbonyl] amino] -1thio-B-erythro-a-B- galacto-octopyranoside (and as monohydrochloride) (lincomycin) 0ι ₈ Η ₃₄ Ν ₂ 0 ₆ 8 A3-2 and its semisynthetic derivative - (28.4K) ^ - {2-chloro-1 - [(2K, 3K, 48.5K, 6K) -3,4,5trihydroxy-6- (methylsulfanyl) oxan-2- il] propyl} -1-methyl-4-propylpyrrolidine-2-carboxamide (clindamycin) Οι ₈ Ο ₃₃ Ο1Ν ₂ Ο ₅ δ 5. The drug according to claim 1, characterized in that the antibiotic A4 is a substance belonging to the class of polyketides with a polyfunctional octahydrotetracene 2-carboxyamide compound, is an antibiotic from the group A1-1 - A1-4, where A4-1 - [48- (4a, 4aa, 5a, 5aa, 6a, 12aa)] - 4- (dimethylamino) -1,4,4a, 5,5a, 6,11,12a-octahydro-3,5, 10,12,12apentahydroxy-6-methyl-1,11-dioxo-2-naphthacene carboxamide (as hydrochloride, monohydrate or cyclate) (doxycycline) Ο ₂₂ Η ₂₄ Ν ₂ Ο ₈ A4-2 - (48.4aK, 58.5aK, 68.12a8) -4- (dimethylamino) -3,5,6,10,11,12a-hexahydro-6-methyl-1,12 dioxo-1,4, 4a, 5.5a, 6,12,12a-octahydrotetracin-2-carboxamide (oxytetracycline) Ο ₂₂ Η ₂₄ Ν ₂ Ο ₉ 6. The drug according to claim 1, characterized in that the antibiotic A5 - a substance belonging to the class of polyketides, the basis of the chemical structure of which is a macrocyclic 14- or 16-membered lactone ring, to which one or more carbohydrate residues are attached, is an antibiotic from Groups A5-1 - A5-2, where A5-1 - 20-deox-20- (3,5-dimethylpiperidin-1-yl) desmicosin phosphate (tilmicosin) - 13,028,412 ^C 46 ^H 8 (^ 2 ⁰ ! 3 -NZROD A5-2 - (3K, 48.58.6K, 7K, 9K, 11K, 12K, 138.14K) -4 - [(2,6-dideoxy-3-C-methyl-3-O-methyl-a- B-ribohexopyranosyl) oxy] -7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-10 - [(E) - [(2-methoxyethoxy) methoxy] imino] -6- [ (3,4,6-tridesoxy-3-dimethylamino-p-O-xylohexopyranosyl) oxy] -14-ethyl-oxacyclotetradecan-2-one (roxithromycin) Ο ₄ ιΗ ₇₆ Ν ₂ Οι ₅ 7. The drug according to any one of claims 1 to 6, characterized in that it is made in the form of a solution in water for injection. 8. The drug according to claim 7, characterized in that it is made in the form of steam sterilized for 45 minutes at a temperature of 100 ° C aqueous solution for injection. 9. The drug according to claim 8, characterized in that it is made in the form of a solution with a pH of 3-5.5. 10. The drug according to any one of paragraphs.8 and 9, characterized in that it is filtered sequentially through filters with a filter fineness of 0.45 and 0.22 μm. 11. The drug according to claim 7, characterized in that it is administered subcutaneously or intramuscularly once a day for 3 days. 12. The drug according to claim 7, characterized in that it is administered in the following doses: calves, lambs, kids, dogs and cats - subcutaneously in a dose of 1 ml per 10 kg of animal weight; piglets - intramuscularly at a dose of 1.5 ml per 10 kg of animal weight. 13. The drug according to any one of claims 1 to 6, characterized in that it is made in the form of a powder for oral administration by drying in a spray dryer.