Antibacterial remedy for the treatment of diseases of agricultural animals and birds, a method for the prevention and treatment of chicks with diseases of bacterial etiology, the treatment of respiratory diseases of calves bacterial etiology, method of prevention of tuberculosis in cattle

 

(57) Abstract:

Group of inventions relates to veterinary medicine. Antibacterial remedy for the treatment of diseases of bacterial etiology of agricultural animals and birds is an emulsion, liposomes, membrane which contains lipids extracted from organs and tissues of cattle, incorporating antibiotic class aminoglycosides in an effective amount for parenteral and oral administration. The method of prevention and treatment of Chicks with diseases of bacterial etiology involves mixing the inventive liposomal streptomycin food and feeding in the first 7 days and at 28-32 days of life birds from the calculation of 14.3-20.0 mg of antibiotic per 1 kg of live weight. A method of treating a respiratory disease of calves bacterial etiology involves intramuscular injection of the inventive liposomal streptomycin once in three days at a dose of 6.20 and 6.25 mg of antibiotic per 1 kg of body weight within 9-12 days. A method for preventing tuberculosis in cattle involves intramuscular injection of animals with a positive tuberculin skin breakdown declared liposomal streptomycin at a dose of 20.0-21,0 mg of antibiotic per 1 kg of live PTO. The invention provides a prolonged effect of the drug, reducing its toxic effects, increasing the effectiveness of antibiotic therapy, including intracellular infection. 4 S. p. F.-ly, 3 tables.

Group of inventions relates to medicines in liposomal form incorporating an antibiotic and can be used for the treatment of agricultural animals and birds of bacterial etiology.

In conditions of mass production of agricultural animals and birds very high probability of infection of their next of pathogenic bacteria (Salmonella enterotidis, E. Coli, Stapfilococcus aureus, Mycobacterium tuberculosis, and others).

These bacteria in vitro is most sensitive to aminoglycoside antibiotics such as streptomycin sulfate.

However, use of this drug is problematic and in clinical practice it is known, its use in combination with other antibiotics, such as penicillin in the treatment of TB (C. M. Navashin, I. P. Fomin. Reference antibiotics, M, "Medicine", 1974, S. 202-212).

This is because, as the antibiotic with bactericidal type of antimicrobial action, streptomycin inhibits the reproduction of only the extracellular raspamecivanje there has been a rapid emergence of resistant to the antibiotic strains of bacteria. Violation of metabolism, resulting from contact of microbial cells with streptomycin, accompanied by the disruption of protein synthesis and diffusion in the environment of amino acids, nucleotides and potassium ions, that is, all factors that inhibit the proliferation of cells or protein synthesis in non-breeding cells, reduce the absorption of streptomycin and weaken its microbial activity.

When the accumulation in the body even small doses of antibiotics may experience severe neurotoxic reactions.

Drugs streptomycin injected into the body parenterally. Use oral antibiotic is poorly absorbed, and in the form of aerosols and per rectum is not absorbed, providing only local effect.

In recent years actively developing the use of therapeutic drugs in liposomal form. This is due to the fact that the drug is included in the liposomal membrane has a prolongation of action and does not cause toxic effects.

The most significant factor in determining the advantages of liposomal carriers over the other, is the functional activity of the lipids forming the membrane of liposomes.

In eternam the treatment of respiratory tract liposomes, consisting of phosphatidylcholine and cholesterol, normal level of laktan in the blood, prevents the development of acidosis, inhibited the peroxidation processes.

Suppressive activity to microbicide environment against bacteria possess phosphatidylserin or lysophosphatidylserine.

The important role of glycolipids (gangliosides) involved in intercellular interactions and which specific receptors for biologically active substances (A. C. USSR N 1699343, A 61 K 9/127, 15.12.91, bull. N 46; C. I. Shvets, Y. M. Krasnopolsky, Vestn. Acad. the honey. of Sciences of the USSR, No. 6, 1990, S. 19-28).

Receptor properties of gangliosides used in a method of producing liposomes incorporating therapeutic drugs for selective delivery to specific organs (A. C. USSR N 1022357, A 61 K 9/10 A 61 K 35/12, 30.12.83, bull. N 48).

The organotropism of drugs is achieved by mixing phospholipids and cholesterol, are selected from a certain amount of living tissue, and subsequent introduction into liposomes active substances the introduction of gangliosides extracted from the same amount of the same cloth.

The results of studies of the effect of the multiplicity of the introduction of liposomes containing antimicrobial drugs is) and saturation them parenchymatous organ compared with free tetracycline, which almost every 8-12 hours after injection were derived from the liver. Looking at the distribution of liposomes composed of lipids parenchymatous organs, the microorganism is evidence of more active capture fabrics vesicles containing phospholipids homologous organs (Rotov K. A. and others Genetics and biochemistry virulence of the causative agents of especially dangerous infections (Proceedings of the Russian scientific conference, Volgograd, 1992, S. 204-205).

Currently known compositions and methods for producing liposomal drugs. When this membrane liposomes contains a complete set of synthetic phospholipids and glycolipids, in liposomes encapsulated with any biologically active substances, including antibiotics, vaccines (RF Application N 96113086/14, A 61 K 9/127, 27.10.98, bull. N 30; U.S. Pat. RF N 2120795, A 61 K 9/127, 27.10.98, bull. N 30).

Selective delivery of drugs is carried accession to the composition of the ligands or fragments from the group consisting of sugar, glycolipid and protein.

Practical use of such compositions requires in each case a careful balancing of the lipid composition of membranes and attached to them fragments.

Known antiviral drug for A from phosphatidylcholine and cholesterol (RF Application N 96108008/14, A 61 K 9/127, 38/21, 20.07.98, Bull. N 19).

The delivery mechanism, the oral application of liposomal drug includes the sealing of pharmaceutical substances in the stomach and increase his "affinity" and "absorption" to the villas, i.e. the leaves of the holes of the lymphatic vessels in the intestinal membranes, so that the substance absorbs into the lymphatic system.

This tool is not effective in the treatment of diseases of bacterial etiology.

Closest to the claimed antimicrobial agent is streptomycin included in liposomes, membrane which is formed on the basis of lecithin. (Vladimir N. A., Ladygina, A., ANCOVA A. I. "Antibiotics", N 1, 1983, S. 23-26).

Antibacterial efficacy of liposomal streptomycin were studied in experimental tuberculosis in mice of BALB/c and CBB6F1infected with a 3-week culture of a virulent strain of Mycobacterium tuberculosis. Thus investigated the number of colonies of mycobacteria in the lungs and spleen, loss of body weight, sensitivity to the toxic effect of intravenous liposomal solution of streptomycin.

Increased antibacterial activity of streptomycin, including avannah in the tissue of the spleen, which indicates, first, the prevalence in the tissue of the spleen intracellular populations of mycobacteria in respect of which the solution of streptomycin light, secondly, about the capture of liposomes main bodies of the monocyte-faguoqitirute system.

Identified slow weight loss in mice with liposomal antibiotic therapy.

When the same doses of liposomal and streptomycin solution 1000 μg per mouse, liposomal drug did not lead to the death of animals, the use of a solution of streptomycin caused weight loss and death of animals. This is because streptomycin, limited lipid membrane is not in contact with the sensitive cells of the nervous system, and with the release of the antibiotic due to the destruction of the lipid membrane enzyme systems of the organism to its concentration in the nervous system do not reach toxic levels.

The results of these studies determine the prospects of a development of liposomal forms of antibacterial drugs.

To date, the main technological methods of obtaining liposomes by the method of treatment phases of various synthetic lipids or mixtures thereof, the introduction of liposomes is th, C. I. Efremenko, V. A. Melnikov, and other Preparation of liposomes containing biologically active substances (Methodical recommendations), Volgograd, 1982; Liposomes (synthesis, properties, aspects, applications in biology and medicine), M, VINITI, N Dept. hands. 3733-V from 18.12.98, 263 S.).

The use of antibacterial drugs for diseases of bacterial etiology poultry is very problematic, as it is practically applicable drug oral or ingalatore.

In terms of poultry farms observed high mortality of birds, especially during the first 10 days, and 28-32 day life of chickens, despite the traditional methods of treatment with tetracycline.

The most common pathogenic bacteria for chickens are Salmonella enterotidis, E. coli, Stapfilococcus aureus.

There is a method of prevention and treatment of infectious diseases of poultry, which in aerosol drug containing as an anti-infective biologically active substances, antibiotics and products of the incubation of the serum of birds, as well as operational additions to ensure the homogeneity and stability of the spray drug - options a mixture of glycerin with dimethylene. Aerosol inhalation for prophylaxis spend chickens ranging in age from 1 day to 2 months. Diseases of chickens treated every 10 days at least 4 times, regardless of the day of vaccination. As antibiotics tested almost all classes, but the most effective was the gentamicin of class aminoglycosides.

The experimental tests on poultry synergistic action of biologically active components provided in the preventive measures the reduction in mortality at 5-6% and a gain of 12.5%, in the treatment of infectious diseases (Salmonella, colibacteriosis) - 9-12% and 11.4%, respectively.

The disadvantages of this method is the complexity of making the expensive drug, a great consumption of drugs, the need for poultry inhalation chambers. Not excluded in the mass procedures, the possibility of inaccurate dosing and toxicity.

High preventive therapeutic efficacy achieved by inhalation of chickens with experimental colibacteriosis when you use drug treatment, in which the active component is used antibiotic class aminoglycosides (gentamicin sulfate), as activerelation activity of aminoglycoside antibiotics and macrolides groups in relation to the standard test cultures and strains of Escherichia coli, pathogenic for birds, is achieved through the use of supplements. When this antibiotic is readily absorbed in the body and long circulates in it.

The disadvantages of this method are the high consumption of antibiotics, the need in inhalation chambers, the possibility of inaccurate dosing and toxicity.

Known oral routes of administration of therapeutic drugs to the birds. As therapeutic drugs are used a mixture of biologically active components, such as products culturing lymphoid cells chickens (U.S. Pat. RF N 2034565, A 61 K 38/21, 35/14, 10.05.95, bull. N 13). Use of this drug (galifinakas, THE 107077191-91) in complex with antibiotics when their average activity is inefficient, and increased activity of the drug is not economically feasible.

The closest in purpose is a method of treatment of diseases of infectious origin (salmonellosis, laryngotracheitis, colibacteriosis, and others ). (Veterinary medicines. Handbook - M., 1998, S. 295).

The method comprises the oral administration of therapeutic drugs. The product contains 4.5 g of phosphate, tisina, 10 g furazolidone, 10 g of tetracycline hydrochloride, 0.02 g of sodium Selenite, 8 g of citric acid, 2 g vitamin aktivnosti treatment, due to the fact that antibiotics for oral administration of poorly absorbed by the body quickly and can be derived from it. Tetracyclines mechanism of action is bacteriostatic and inhibit the reproduction of only the extracellular located pathogens. It is not excluded inaccurate dosage and toxicity.

In terms of mass production of cattle (cattle) the greatest economic damage inflicted by the disease. The complexity of TB is the duration of the incubation period of the disease, the slowness of reproduction and resistance in the external environment. The main diagnostic test for mass screening of animals currently serves as allergic test for tuberculin. However, the tuberculin react not only infected with pathogenic mycobacteria animals, but also sensitized acid saprophytes and atypical mycobacteria. All malicious external factors lead to disorder of homeostasis, infection, stimulating the growth of the causative agents of tuberculosis and atypical mycobacteria in cattle and calves. All these factors contribute to the relevance of the prevention and treatment of ill used orally in the form of briquettes containing erythromycin, starch, calcium stearate, doxylin, lactose (U.S. Pat. RF N 1424170, A 61 K 31/71, 20.12.95, bull. N 35).

Trials of the drug in experimental pulmonary infection caused by Escherichia coli and Streptococcus, white mice, showed the effectiveness of the treatment 60-100%.

Practical application of the drug is limited by its high cost, difficulty of preparation. In addition, the antibacterial efficacy is insufficient to intracellular infection.

Well-known drug for treatment of animals (calves, piglets), patients with leptospirosis, pneumonia, bronchopneumonia (U.S. Pat. RF N 2053772, A 61 K 31/65, 10.02.96, bull. N 4).

The drug is prepared on the basis of tetracycline entered into his composition for prolongation of action and stimulate the immune activity of the organism by polyvinylpyrrolidone, 1,2-propane diol and dimethyl sulfoxide.

Comparative tests using tetracycline extended and neprolongirovannymi steps in the treatment of calves with clinical signs of pneumonia showed that when the same dose 1 injection of 10 thousand UNITS of antibiotic per 1 kg of weight of animal healing occurs in the first case, after 2-3 injections with an interval of 72 h, and the second after 14 Ino effective against intracellular located pathogenic bacteria.

The closest in purpose to the claimed method of treatment of respiratory diseases of calves bacterial etiology is a method of treating pneumonia of calves infected with pneumococci (Rotov K. A., Sitnikov, N. M., Tikhonov N. , And other Diagnostics, treatment and prevention of infectious diseases, biotechnology, veterinary medicine. Materials jubilee scientific conference, dedicated to the 70th anniversary of the Institute of Microbiology of the Ministry of defense. Kirov, 1998, S. 418).

The research used the 53 heads of calves up to 6 months with bacteriological indicators of pneumonia. The number of leukocytes in all infected animals exceeded 13.4109/l (normal 8-9109/l).

In the experimental group treated with a suspension of liposomes based on lecithin put into vesicles streptomycin sulfate, the drug was administered intramuscularly at a dose of 0.002 g of streptomycin per kg body weight of 1 times a day for 5 days.

After the first course of treatment in 60% of animals returned to normal levels of leukocytes in the blood.

After re-treatment after 2 months the leukocyte counts were normalized in 79.2%, after the third year, 2 months leukocyte count returned to normal in 85.6% of all calves CLASS="ptx2">

In the control group of animals were treated by intramuscular injection of streptomycin solution at a dose of 0.01 g/kg body weight 2 times a day for 7 days, and the animals did not receive the drug. After 6 months in both the control subgroups were killed over 80% of calves from pneumonia.

The results of experimental studies suggest on the one hand the efficiency of the use of liposomal forms of the antibiotic, the other lead to the need for changes in treatment with a targeted increase in the share of absorption and preservation of drug concentration in macrophages mononuclear system.

For the prevention of tuberculosis of cattle in the whole complex of veterinary-sanitary measures in the period of 1980-1985, almost all the major regions of Russia conducted field tests of various methods for isoniazid (tubazide) and BCG vaccine.

Isoniazid has a high bacteriostatic properties to Mycobacterium tuberculosis. The drug was administered orally, mixing dry food or water, skim milk or by subcutaneous injection tubesing suspensions that constitute a complex preparation containing tubazide and vitamin AP> Chemoprophylaxis has not found wide application because of their complexity, lack of effectiveness, high cost drugs. Re-introduction in many cases caused desensitization of the body and after the termination of their use dramatically increased the number of reacting to tuberculin in animals, and also led to the emergence of strains of Mycobacterium tuberculosis that are resistant to medicines.

Tuberculostatic drugs based on isoniazid cause L-transformation of mycobacteria, which after the termination of these funds are returned in the original bacterial form, causing a relapse.

The BCG vaccine is also not efficient enough for mass immunization of cattle from several disadvantages, including long-term preservation of vaccine-related allergic reactions and lack of methods for their differentiation from tuberculosis (Instructions for use tubeside and tubeside-streptomycin suspension for chemoprophylaxis of tuberculosis in cattle, appr. GAWSH USSR 08. 04. 81; B. A. Soloviev, N. P. Ovdienko, Veterinary, N 12, 1991, S. 3-6; B. M. Avilov, V. F. Pilinis, Veterinary Medicine, No. 1, 1992, S. 3-9).

Application tubeside and tubeside-streptomycin suspension has rcrs, caused by infection bullish view and if the selected culture mycobacteria are sensitive to tubazide. Treatments suspensions subjected only animals who do not respond to the TB and no clinical signs of disease. The suspension is administered to the animals subcutaneously with 3-4 days of age, 1 in every 30-35 days prior to the formulation of the herds in the control study at a dose of 0.05 ml per 1 kg of live weight. Before use vials suspension is heated in a water bath at 34-50oC and thoroughly shaken.

The simultaneous use of BCG vaccine and suspension of tubazide is unacceptable, because the effect of one drug may weaken the effectiveness of the other (N.C. Khazipov, M. A. Safin, G. H. Gurinov, Tuberculosis, cattle, M, Agropromizdat, 1985, S. 117-119).

The known method of prevention of tuberculosis calves by subcutaneous injection of isoniazid-based bactericide at a dose of 10 mg/kg body weight, the content of isoniazid with an interval of 8-12 days within 3 months. Acterized is a derived from the oxidation of water-soluble antibacterial fractions of fish oil (A. C. USSR N 1825629, A 61 K 35/60, 45/96, 07.07.93, bull. N 25).

The use of the proposed acterized provides the effect of prolongation voicereminder tuberculosis and in a controlled epidemiological experience on the calves, obtained from TB patients cows.

The massive use of this method is limited not only by the high cost of the drug and complexity, but not reliable prevention due to the fact that the drug has no effect on intracellular bacteria, there is a possibility of emergence of resistant to the drug strains of recurrences of the disease.

Veterinary practice found that in infected calves, the disease usually progresses in adulthood after the first and second calving. In this pattern manifestations of tuberculosis among reproductive population is one of the reasons for relapse in treated plots. The group's aim of the invention is the choice of the most efficient remedies for antibiotic therapy of diseases of farm animals and poultry bacterial etiology, improve prevention and treatment of chickens, treatment of respiratory diseases of calves, prevention of tuberculosis in cattle and calves.

This objective is achieved in that the antibacterial remedy for the treatment of agricultural animals and birds bacterial etiology before otravnych animals (brain, liver, kidney cattle), incorporating antibiotic class aminoglycosides, such as streptomycin sulfate, in an effective amount for parenteral and oral administration.

The method of prevention and treatment of Chicks with diseases of bacterial etiology includes oral administration of the emulsion, liposomes, membrane which contains lipids extracted from organs and tissues of warm-blooded animals (brain, liver, kidney cattle) incorporating antibiotic class aminoglycosides, such as streptomycin sulfate, in an effective amount, by mixing it with food and feeding in the first 7 days and at 28-32 day in the life of birds is based 14.3-20.0 mg of antibiotic per 1 kg of live weight.

A method of treating a respiratory disease of calves bacterial etiology involves intramuscular injection of the emulsion, liposomes, membrane which contains lipids extracted from organs and tissues of warm-blooded animals (brain, liver, kidney cattle) incorporating antibiotic class aminoglycosides, such as streptomycin sulfate, in an effective amount, once in three days at a dose of 6.2-6.25 mg of antibiotic per 1 kg of body weight within 9-12 days.

Method of prevention of tuberculosis in the wound which contains lipids, extracted from organs and tissues of warm-blooded animals (brain, liver, kidney cattle) incorporating antibiotic class aminoglycosides, such as streptomycin sulfate, in an effective amount, the dose of 20.0-21.0 mg of antibiotic per 1 kg of body weight every three days for 2 months with simultaneous oral use of tubazide with food.

With respect to the prototypes of the claimed group of inventions has the following distinctive features.

Use for constructing the membrane of liposomes lipids isolated from organs and tissues of warm-blooded animals, such as brain, liver, kidney cattle, provides a balanced equimolar ratio of all types of lipids and maximize their functional activity in relation to the various organs of the host, which creates optimal conditions for antibiotic treatment of intracellular infections. It is known that in a mixture of lipids isolated from the white matter of the brain bulls, contains 50% cholesterol, cerebroside, phosphatidylethanolamine, the rest is phosphatidylcholine (lecithin), phosphatidylinositol, phosphatidylserine and lipids of vegetable origin, such as soybean, contain almost 87% of phosphatidylcholine (Oan liposomes provides a relatively stable sealing of the antibiotic in the stomach after oral administration with a gradual transition and its absorption into the lymphatic system.

Thus, the claimed as an antibacterial agent liposomal streptomycin has a number of advantages.

The ability to use the drug both parenteral and oral.

Ensuring prolongirovannomu steps, the reduction of the applied dose of the drug, reducing its toxic effects.

Increase the effectiveness of treatment due to the transport of the antibiotic into the cells of the microorganism, which often localized infectious agents.

Oral use of the claimed Antibacterials in the first 7 days and at 28-32 day life birds caused the most severe effects of pathogenic microorganisms on the body of birds in these periods.

The dose of injected birds of antibiotic incorporated in liposomes, 14.3-20.0 mg per 1 kg of live weight is therapeutically necessary and sufficient for cure and prevention.

A lower dose of antibiotic below the proposed limit reduces the effectiveness of its action, the increase is impractical.

Prolongation and the efficiency of liposomal drug provides significant economic benefits by reducing consumption is the Prime treatment calves diseases of bacterial etiology intramuscular liposomal streptomycin the inventive method differs the membrane of liposomes contains lipids of animal origin, the course of treatment consists of 3-4 fold injection (1 every 3 days) at a dose of 6.20-6.25 mg of antibiotic per 1 kg of live weight. The combination of these methods provides a more effective antibiotic therapy, including intracellular infection.

The dose of injected antibiotic 6.20-6.25 mg per 1 kg body weight of 1 times in 3 days is therapeutically necessary for healing. A lower dose of antibiotic below the proposed limit reduces the efficiency and prolongirovannomu his actions, increasing as it does not make sense.

The main features of the proposed method for the prevention of tuberculosis in cattle in relation to accepted veterinary practice methods is intramuscular injection of animals with a positive tuberculin breakdown of the emulsion, membrane which contains lipids extracted from organs and tissues of warm-blooded animals (brain, liver, kidney cattle), incorporating antibiotic class aminoglycosides, such as streptomycin sulfate, in an effective amount, the dose of 20.0-21.0 mg of antibiotic per 1 kg of body weight every three days for 2 months.

Combined use claimed tuberkuleznyj and atypical mycobacteria, including localized intracellularly.

The dose of injected antibiotic 20.0-21.0 mg per 1 kg body weight of 1 times in 3 days is therapeutically necessary and sufficient for prolongirovannomu and the effectiveness of its actions.

The possibility of practical use of the claimed group of inventions is confirmed by the examples of their particular perform.

Example 1. Preparation of antibacterial therapeutic agents. 10 kg of the brain or the liver, kidneys, lungs cattle homogenized and the resulting mass is poured a mixture of 16.7 liters of methanol and 33.3 liters of chloroform in the ratio of 1:5. The mass extracted by stirring at room temperature for at least 5 hours Separating the extract and add 1 l of 0.7% solution of sodium chloride (20% by volume of the extract). The resulting solution is stirred and defend 2-3 h to dissolve the protein fractions. After stratification system on the 2nd fraction is separated bottom fraction containing lipids. Determine the number of lipids by weight of dry residue, it is 30-50 mg/ml

In liter flask is filled with 23.7 ml of extract lipids and evaporated on a rotary evaporator to remove the azeotropic mixture and formation of a film of lipids on the surface of the glass bulb. Then wash off the dried limes the buffer pH 7.2). Stir the mixture to dissolve the precipitate. The contents poured into a glass, add 459 mg of cholesterol from the calculation of the molar ratio of the extract of lipids and cholesterol, is 7: 2), 45 ml of the antibiotic dissolved in phosphate buffer pH 7.2 (125 mg/ml suspension of liposomes at 70% the inclusion of substances in vesicles) and process the mixture in an ultrasonic disintegrator at a power of 200 watts 20 kHz for 5 minutes the Emulsion was poured in a liter round-bottom flask, attach it to the rotary evaporator and evaporated under vacuum while rotating the flask in a water bath with a temperature of at least 40oC. the Evaporation is conducted at least 40 min until complete disappearance of the smell of an organic solvent. Then the flask contribute 3-5 pieces of glass beads and wash the formed gel rotational movements before the formation of a homogeneous emulsion. The emulsion is subjected to methods of gelchromotography and ultracentrifugation purification from neuklyuzhego material and the concentration of liposomes. The contents of the flask was poured into the beaker and the volume was adjusted to 150 ml of phosphate buffer pH 7.2. Using bacteriological method to control the degree of inclusion of the antibiotic in the vesicles, it should be not less than 70%. Prostateline research in the treatment of broiler chickens on the basis of the Stavropol poultry.

In experiment investigated 900 chickens with an average weight of 35 g, 300 of which were treated traditionally with the use of tetracycline, 300 - using streptomycin sulfate liposomalna, 300, the control group without treatment.

The observations were carried out during the first 7 days of life Chicks.

For the 2nd experimental group liposomal emulsion streptomycin, prepared according to example 1, in the amount of 1.3 ml (15 mg of antibiotic per 1 kg of live weight when the content of the drug in the emulsion, liposomes 125 mg/ml), which was and stirred in 10 l of tap water (20-25oC), then uniformly mixed with the specified feed. Therapeutic food fed to Chicks on an empty stomach in the early hours, controlled shedemei, food and temperature regimes.

In table. 1 shows the results of the experiment on the gain and loss of poultry in 7 days after treatment.

As the data table. 1, mortality of birds in the group N 2 compared to group # 1 and group # 3 has decreased more than 4 times, the increment in group N 2 17% higher than the group N 1 and 32% higher than the group N 1. In the group using tetracycline compared to the control is observed with increasing gain increases Pade and experimental observations experimental group (15000 chickens) using liposomal streptomycin and control group without treatment (15000 chickens) in the first 7 days and at 28-32 day of life for poultry.

Treatment was performed similarly to example 2, except that in the first 7 days and at 28-32 days used daily amount of emulsion 20.0 mg of antibiotic per 1 kg of live weight.

In table. 2 shows the experimental results characterizing the efficiency of liposomal drug to reduce mortality and increase weight gain of poultry.

Example 4. Carried out experimental research in the production environment 7 workshops in which the experiments were 36 thousand chickens. In six workshops conducted treatment liposomal streptomycin at 1-7 and 28-32 days of life. In seventh workshop of the observed control group without treatment. The treatment was carried out analogously to examples 2, 3 based 14.3 mg of antibiotic per 1 kg of live weight.

In table. 3 shows the results of an experimental treatment to reduce the mortality of the big party Chicks, located in different shops.

The results of the experiments are given in table. 1-3 show about effective therapeutic and biological action of streptomycin sulfate liposomal manifested in a significant reduction in mortality in the 1.3-1.5 times and increased weight gain of poultry. The economic benefits of treatment of chickens by liposomal, in General reducing bird deaths from 21 to 15% and increase the weight of the birds compared to the control lot 95 g on the head.

Example 5. Experimental studies in the treatment of respiratory diseases in calves bacterial etiology on the basis of former collective farm them. S. M. Kirov, Soviet district of the Stavropol territory. In experiment investigated 20 calves at 6 months of age with clinical indicators of respiratory disease and with a positive reaction to tuberculin. Treatment of calves was performed by intramuscular injection of liposomal streptomycin sulfate 1 time in three days in a dose of 0.25 mg antibiotic or 0.05 ml of the emulsion prepared according to example 1, 1 kg of live weight. 9-12 day clinical signs of disease in all animals was absent. After treatment calves was made tuberculin skin test and 5 were selected sera from animals with a negative intradermal tuberculariaceae breakdown 5 sera from dubious and 5 sera with positive break. All sera were tested for the presence of antibodies to tuberculosis by counter immunoelectrophoresis (WIEF), by reaction of an indirect immunofluorescence assay (NIF), a competitive reaction immunoediting (CED). As a result of the research the globulin was not detected.

Example 6. Experimental study in the prevention of tuberculosis in DAC on the basis of former collective farm them. S. M. Kirov, Soviet district of the Stavropol territory. For conducting experiments selected 21 head of cows respond positively to a tuberculin test and intended for the sanitary-veterinary norms to slaughter.

Within 2 months of each cow in two days on the third day was introduced 20.5 mg of streptomycin or liposomal 0.16 ml emulsion per 1 kg of live weight, prepared according to example 1, intramuscularly. At the same time the feed was set to 20 g of tubazide on the head. During the course of treatment complications in experimental animals was not observed, not decreased milk yield, which after boiling was sent to feed the calves. On the 5th day after treatment the animals were examined for TB, 18 cows reaction was negative, 3 - slabopolojitelen. Repeated studies after a month showed the same results.

Positively reacting to tuberculin animals were killed, the causative agent of tuberculosis has not been allocated microscopic, bacteriological and biological methods. With 18 cows lifted the quarantine and transferred them to the common herd.

Thus, the claimed group isobell will be able to improve the number of animals and birds, but will be a significant economic effect.

1. Antibacterial remedy for the treatment of diseases of agricultural animals and birds, representing emulsion, liposomes incorporating antibiotic class aminoglycosides in an effective amount, wherein the membrane of liposomes contains lipids extracted from organs and tissues of cattle.

2. The method of prevention and treatment of Chicks with diseases of bacterial etiology, including oral administration of the drug containing the antibiotic, characterized in that as drug use antibacterial under item 1, the drug is mixed with food and fed in the first 7 days and at 28 - 32 day in the life of birds is based 14,3 - 20,00 mg of antibiotic per 1 kg of live weight.

3. A method of treating a respiratory disease of calves bacterial etiology, including intramuscular injection, contains the antibiotic, characterized in that as drug use antibacterial under item 1, when the drug is administered once in three days at a dose of 6.20 and 6.25 mg of antibiotic per 1 kg of body weight for 9 to 12 days.

4. Method of prevention of tuberculosis in the positive tuberculin skin breakdown additionally injected intramuscularly antibacterial under item 1 of the calculation of 20.0 - 21,0 mg of antibiotic per 1 kg of body weight once in three days for two months.

 

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