Medication for colibacteriosis treatment for young farm animals

FIELD: veterinary.

SUBSTANCE: medication includes the following components, wt %: Sulfadimezinum 11.5-15; Trimethoprim 2.0-3.6; Colistin 2.0-3.5; glucose up to 100. Before application the medication is dissolved in warm water or colostrums at 35-37°C or fed with forage. The medication is applied daily twice in the dosage of 100 mg/kg of body weight for 3-5 days, or for 5-7 days under severe course of disease.

EFFECT: enhanced efficiency of colibacteriosis treatment for form animals.

12 tbl, 4 ex

 

The invention relates to the field of veterinary medicine.

Currently one of the leading problems are diseases of young farm animals, manifested by diarrhea syndrome and steadily take the leading place among all bacterial infections are registered in all countries and for economic damage to livestock, ranked second in the world.

Gastrointestinal diseases calves cause a great damage to livestock due to the high morbidity and mortality (up to 100%), cost of medical activities, reducing the productive qualities and breeding value of animals.

In the complex of actions on prevention of gastrointestinal diseases of bacterial etiology in young farm animals has been widely used for such chemotherapeutic agents: sulfonamides, antibiotics, nitrofurans, but the best effect is achieved with the use of complex products.

It is known that a wide range of antimicrobial activity of drugs, as a rule, is achieved by combining multiple drugs. The combination of chemical structures in the composition allows to achieve their energichnogo effect that can reduce the dose of the drug and thus reduce the risk of side effects or get drugs with new useful the properties.

Known analog - antibiotic "Self Granules for the treatment and prevention of gastrointestinal diseases of young animals, which contains, wt%: The sulfadiazine 10,0, Trimethoprim 2,0, rest excipient [Veterinary drugs in Russia: a Reference book in 2 volumes. T.I / Irakleiou, Clallam, Nuarimol, I., Arkhipov. - M: Selhozizdat, 2004. - S].

Also known for the treatment of gastrointestinal diseases of young farm animals "Trimerized", contain an antibacterial agent wt.%: Sulfamerazine 10,0, Trimethoprim 2,0, rest excipient [Reference 2 volumes. T.I / Irakleiou, Clallam, Nuarimol, Youripod. - M: Selhozizdat, 2004. - S].

The use of these drugs does not always produce a positive therapeutic effect. This may be due to the development of resistance of pathogens to these drugs.

The prototype of the invention is the drug "Trimethadione"containing, wt.%: Sulfamethoxazole 10,0, Trimethoprim 2,0, rest excipient [Reference 2 volumes. T.I / IVAN maple, K.L. Maltsev, N.A. Yaremenko, I., Arkhipov. - M: Selhozizdat, 2004. - S].

This medicine is not always sufficiently effective and leads to incomplete recovery of calves and piglets.

As pharmacodynamic Spa is Tr y of this drug is less pronounced, which leads to decreased efficiency and result in incomplete recovery of calves and piglets.

Technical result - improving the treatment of colibacillosis in farm animals.

The technical result is achieved by the use of the drug consisting of the following components, wt%:

Sulfadimezin - 11,5-15

Trimethoprim - 2,0-3,6

Colistin - 2,0-3,5

Glucose - 100%

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

Sulfadimezin to 12.0

Trimethoprim - 2,4

Colistin - 3,0

Glucose is 100.

The rationale for this combination is due to the fact that simultaneously combines three of antimicrobial drug with a different mechanism of action, and this in turn provides synergenic effect.

Sharing sulfadimesine with trimethoprim causes bactericidal effect and increases the antibacterial effect of colistin in conjunction with this composition that provides quick recovery, reducing consumption of active substances and their side effects.

Sulfadimezin - 2-(para-Aminobenzoyl-sulfamido)-4,6-dimethylpyrimidin. Due to the structural similarities of the molecules are para-aminobenzoic acid and sulfonamides last able to displace PABK of the enzyme systems of the organism. Under its action in the microbial cell is disturbed with ntes methionine, purine and pyrimidine bases, which in turn leads to disruption of the synthesis of nucleic acids and nucleoproteins. Also inhibits dihydrofolic acid synthesis in the organism of glutamine and paraminobenzoic acids. [Mashkovsky PPM Medicines. - 12th edition. M: Medgiz, 1999. - 326 S.]

Trimethoprim is a competitive inhibitor digidrofolatreduktazy and violates one of the stages of the synthesis of nucleic acids is the formation of tetrahydrofolate acid from digidrofolieva [Mashkovsky PPM Medicines. - 12th edition. M: Medgiz 1999. - 335 S.]

Colistin (polymyxin E) has a direct effect on the cytoplasmic membrane of microorganisms adsorbed on its phospholipid components that contributes to the violation of its permeability and release in the environment of water-soluble components of the cytoplasm [Schetinin E.V. Polymyxins - a new look at a well-known antibiotics. Clinical Microbiology and antimicrobial chemotherapy. No. 3. volume 2. 2000, 68-73 C.].

Glucose is a source of easily digestible by the body and energy of a material that increases the body's resistance and improves its functions. Glucose is the chemical formula

Is a white powder. Very easily soluble colorless crystals or a white crystalline is Orasac odorless, sweet taste. Soluble in water (1:1.5), trudnorastvorim in alcohol. Solutions are sterilized at a temperature of 100°C for 60 minutes or at a temperature of +119, +121°C for 5-7 minutes: pH solutions 3,0-4,0 [Mashkovsky PPM Medicines. In two parts. P.II. - 12th ed. revised and enlarged extra - M.: Medicine, 1994. - S.219-220].

Drug for the treatment of colibacillosis in young farm animals before dissolving in warm water, colostrum temperature of 35-37aboutWith or fed with food. The drug is administered daily twice a day in a dose of 100 mg/kg body weight for 3-5 days, with severe disease within 5-7 days.

In recommended doses, the drug causes no side effects and complications.

Not permitted simultaneous or sequential use of the drug for the treatment of colibacillosis in young farm animals with other OTO - and nephrotoxic drugs (kanamycin, neomycin), and severe renal impairment.

The drug is contraindicated in hypersensitivity animals to colistin. Slaughter of animals for meat is allowed not earlier than 14 days after the last injection of the drug. Meat animals, forced killed before the expiration of the specified term, may be used to feed carnivorous animals or for the production of meat and bone meal./p>

Made the drug for the treatment of colibacillosis in young farm animals as follows. First, in the capacitance type trimethoprim, then with vigorous stirring sulfadimezin, leading to complete mixing, and then colistin. All mixed until a homogeneous powder and then add the glucose. The process is stopped when everything is completely mixed.

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

Studied the antimicrobial properties of the drug. The optimal quantitative content sulfadimidine with trimethoprim and kolistinom in experiments in vitro and in vivo. In model experiments revealed that the drug has a broad spectrum of antibacterial activities against the tested cultures of microorganisms.

In vitro experiments

Study of antimicrobial activity and the ratio of components in the drug for the treatment of colibacillosis in young farm animals were carried out in vitro by serial dilution method. As the test cultures used reference (Museum) and field (pathogenic) strains of micro-organisms - pathogens of the gastro-intestinal diseases of pigs and calves, typed on morfologica is Kim, tinctorially, cultural, biochemical and serological properties. The ratio of sulfadimesine, trimethoprim, colistin in the drug for the treatment of colibacillosis 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.%:

Sulfadimezin - 15,0

Trimethoprim - 3,0

Colistin - 2,5

Glucose - 100

The combination of the 2 is part of the preparation for the treatment of colibacillosis in young farm animals; components, wt.%:

Sulfadimezin to 12.0

Trimethoprim - 2,4

Colistin - 3,0

Glucose - 100

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

Sulfadimezin to 12.0

Trimethoprim - 3,0

Colistin - 3,0

Glucose - 100

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

Sulfadimezin - 11,5

Trimethoprim - 2,0

Colistin - 2,0

Glucose is 100.

Antimicrobial activity of different combinations of the composition of the drug was compared with the antimicrobial activity of sulfadimesine, trimethoprim, colistin.

Minimum inhibitory concentration (MIC) of the studied drugs was determined by the method of serial spy who s in mesopatamia broth (BCH).

The results of the study of antimicrobial activity of sulfadimesine, trimethoprim, colistin and different compositions of the drug for the treatment of colibacillosis in young farm animals are presented in table 1.

As can be seen from the presented data, the drug has a high antibacterial activity against the major pathogens of the gastro-intestinal diseases of young farm animals. Depending on the strain minimum inhibitory concentration (MIC) against S.cholerae suis amounted to colistin 0.78 µg/ml, for sulfadimezina - to 50.0 μg/ml for trimethoprim - 25,0 mg/ml

Antimicrobial activity of the composition 1 in weight in relation to S.cholerae suis decreased in comparison with kolistinom 32 times compared to sulfadimezinom increased 2 times as compared with trimethoprim has not changed. But at the same time, the combined use of colistin, sulfadimezina and trimethoprim is possible to reduce the MIC in relation to the culture for sulfadimezina to 18.3 µg/ml, for trimetoprima to 3,66 µg/ml against Escherichia absolute mass of the drug active composition 1 was decreased compared to kolistinom 8 times as compared with sulfadimezinom and trimethoprim increased in 2 times. But at the same time, the combined use of colistin, solved Mesina and trimethoprim is possible to reduce MICK for sulfadimezina to 9.15 mg/ml, for trimetoprima up to 1.83 mg/ml, for colistin - up activity of the substance (of 1.52 mg/ml).

Antimicrobial activity of compositions 2 in weight in relation to S.cholerae suis decreased in comparison with kolistinom 16 times, compared to sulfadimezinom increased by 4 times as compared with trimethoprim - 2 times. But at the same time, the combined use of colistin, sulfadimezina and trimethoprim is possible to reduce MICK for sulfadimezina to 8.62 mg/ml for trimethoprim - to 1.72 mg/ml, for colistin - to 2.16 µg/ml against Escherichia absolute mass of the drug active composition 2 was decreased compared to kolistinom only 2 times as compared with sulfadimezinom and trimethoprim increased 8 times. And at the same time, the combined use of colistin, sulfadimezina and trimethoprim is possible to reduce MICK for sulfadimezina up to 2.15 mg/ml (above the active substance 12 times), trimethoprim - 0.43 µg/ml (above the active substance in 58 times)for colistin - to 0.54 µg/ml, which is above the active substance 2.9 times.

Antimicrobial activity of compositions 3 in weight was similar to composition 1 in respect of Salmonella and Escherichia. But at the same time, the combined use of colistin, sulfadimezina and trimethoprim is possible to reduce MICK concerning Salmonella for sulfadimezina to 16.7 ág/ml (above activity is ubstance 3 times), for trimethoprim - up to 4.16 mg/ml (above the active substance 6 times). The combined use of colistin, sulfadimezina and trimethoprim is possible to reduce the MIC against Escherichia for the sulfadimesine 8.33 μg/ml (above the active substance 3 times), trimethoprim - to 2.08 mg/ml (above the active substance 12 times).

Antimicrobial activity of the composition 4 was lowest. In weight in relation to S.cholerae suis decreased in comparison with kolistinom 64 times, compared with sulfadimezinom has not changed as compared with trimethoprim decreased in 2 times. The combined use of colistin, sulfadimezina and trimethoprim in composition 4 was able to reduce the MIC only for trimethoprim - up 7,63 µg/ml against Escherichia, and Salmonella (above the active substance, respectively, 1.6 and 3.3 times).

Thus, the study of antimicrobial activity of the drug and the individual components showed the presence of synergistic action in relation to the studied pathogenic cultures. It is established that the active composition can be considered as composition 2.

In this regard, more detail has been studied antimicrobial activity of the composition 2. The results of the experiment are shown in table 2

Table 2
Antimicrobial activity of the composition 2 (the best part)
Mbsc, ug/mlMBC (µg/ml)
Culture of microorganisms3,126,25
Escherichia coli 57/8536,2512,5
Escherichia coli 0425,050,0
Escherichia coli 0(III) p3,126,25
Escherichia coli 866

The results of these studies showed that the drug has a pronounced antimicrobial action.

1.2 in vivo studies

The study of the optimal ratio of colistin, sulfadimezina and trimethoprim in the drug held in the experiments for the treatment of colibacillosis in pigs in comparison with drug Trimethadione.

The diagnosis of the disease colibacteriosis was established on the basis of the clinical examination of animals, postmortem autopsy, laboratory studies with the epizootic situation in the economy.

For the treatment of pigs in the control group (10 animals) used the trimethadione dose of 0.25 g/kg body weight orally in a mixture with food twice a day for 4 days.

For the treatment of piglets from the experimental group (10 goal. in each) were used drugs with different ratio of colistin, sulfadimezina and trimethoprim.

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

Sulfadimezin - 15,0

Trimethoprim - 3,0

Colistin - 2,5

Glucose - 100

The combination of the 2 is part of the preparation for the treatment of colibacillosis in young farm animals; components, wt.%:

Sulfadimezin to 12.0

Trimethoprim - 2,4

Colistin - 3,0

Glucose - 100

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

Sulfadimezin to 12.0

Trimethoprim - 3,0

Colistin - 3,0

Glucose - 100

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

Sulfadimezin - 11,5

Trimethoprim - 2,0

Colistin - 2,0

Glucose is 100.

The piglets were prescribed medications orally mixed with feed at a dose of 0.1 g/kg of body weight twice a day for 4 days.

The results of the experiment on studying the efficacy of drugs for the treatment of colibacillosis in pigs is presented in table 3.

Table 3
The efficacy of the drug with various proportions of colistin, sulfadimezina and trimethoprim in the treatment of colibacillosis in pigs
IndicatorsCombination drugTrimethadione
1234
The number of animals that goal.1010101010
The duration of treatment, days3,6±0,43,2±0,23,8±0,24,0±0,24,4±0,3
Recovered a goal.
%
9
90,0
10
100,0
9
90,0
8
80,0
8
80,0
Left sick goal.
%
1
10,0
-1
10,0
2
20,0
2
20,0
Palo goal.
%
-----
Therapeutic efficacy, %90,0100,090,080,080,0

In the experience of the piglets in the treatment of colibacillosis confirmed by the higher efficiency of the combination of sulfadimezina, trimethoprim and colistin in the product in the ratio of 12:2,4:3 (combination 2).

Example 2. To study the efficacy of treatment of colibacillosis in calves.

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

The diagnosis of the disease colibacteriosis have established complex on the basis of the clinical examination of animals, bacteriological studies (highlighted in E.coli different serological variants), conducting autopsies taking into account the epizootic situation in the economy.

The animals were daily clinical observation within 10-15 days, when it took into account the General condition, mortality, growth rate, timing recovery.

In the 1st experience calves of the control g is uppy treated "Trimetinom", which is used orally in the dose of 250 mg/kg of body weight twice a day for 4-6 days. In experiments 2 and 3 calves of the control group was treated with the drug "Self granules", which is used orally in the dose of 5 g/20 kg body weight twice a day for 3-5 days.

Animals of the experimental group for the treatment of used drug for the treatment of colibacillosis in young farm animals in the following ratio, wt.%:

Sulfadimezin to 12.0

Trimethoprim - 2,4

Colistin - 3,0

Glucose - 100%

The drug was administered orally in a dose of 0.1 g/kg of body weight every 12 hours for 3-5 days, with severe disease within 5-7 days.

The first experiment to study the effectiveness of treatment of colibacillosis of calves held in a SEC "Staronikolskoe" Khokholskiy district of Voronezh region in February-March 2007.

The second experiment to study the effectiveness of treatment of colibacillosis of calves held in a SEC "Staronikolskoe" Khokholskiy district of Voronezh region in March 2007.

The third experiment to study the effectiveness of the treatment of colibacillosis in calves held in LLC "Commonwealth" novousmansky district of Voronezh region in February 2007.

The results of the experiments are presented in tables 4-6.

Table 4
The effectiveness of the treatment of colibacillosis of calves in the SEC "Staronikolskoe" Khokholskiy district of Voronezh region (1st experiment)
IndicatorsThe group of animals
ControlExperience
The number of animal heads1721
Recovered heads1419
%82,490,5
Palo goals--
%--
Left sick, goals32
%17,69,5
Recovery time, days4,8±0,43,6±0,3
Therapeutic effectiveness, %82,490,5

Table 5
The effectiveness of the treatment of colibacillosis of calves in the SEC "Staronikolskoe" Khokholskiy district of Voronezh region (2nd experience)
IndicatorsThe group of animals
ControlExperience
The number of animal heads2534
Recovered heads1932
%76,094,1
Palo goals--
%--
Left sick, goals62
%24,05,9
Recovery time, days5,1±0,53,3±0,3
Therapeutic effectiveness, %76,094,1

Table 6
The effectiveness of the treatment of colibacillosis of calves in LLC "Commonwealth" novousmansky district of Voronezh region (3rd experiment)
IndicatorsThe group of animals
ControlExperience
The number of animal heads7896
Recovered heads6285
%79,588,5
Palo goals--
%--
Left sick, goals1611
%20,511,5
Recovery time, days4,9±0,33,9±0,5
Ter is non-therapeutic efficiency, %79,588,5

Studies have shown that the drug for the treatment of colibacillosis in young farm animals has a high therapeutic efficacy in the treatment of colibacillosis in calves (on average it amounted 91,0%), 8.0% higher efficacy "Trimethadione, and 11.7% - drug "Self granules" (2 and 3 experience). Compared with control groups using the drug for the treatment of colibacillosis in young farm animals decreased recovery time on average 1.3 days.

Example 3. To study the efficacy of treatment of colibacillosis in pigs.

The study was carried out in three experiments on pigs 2-10 days of age weighing 2.5 to 3.5 kg On the principle of paired analogues animals were divided into two groups with regard to the General condition and the severity of the disease and under the same conditions of feeding and maintenance.

The diagnosis of the disease colibacteriosis have established complex on the basis of the clinical examination of animals, the results of bacteriological studies (highlighted in Escherichia coli of different serological variants), conducting autopsies taking into account the epizootic situation in the economy.

The animals were daily clinical observation for 10-15 d is her this took into account the General condition, mortality, growth rate, timing recovery.

Piglets in the control group was treated with the drug "Self granulate, which is a basic drug in the sample farms. The drug is used orally in the dose of 5 g/20 kg body weight twice a day for 3-5 days.

Animals of the experimental group for the treatment of colibacillosis in young farm animals used the drug in the following ratio, wt.%:

Sulfadimezin to 12.0

Trimethoprim - 2,4

Colistin - 3,0

Glucose - 100

The drug was administered orally in a dose of 0.1 g/kg of body weight every 12 hours for 3-5 days, with severe disease within 5-7 days.

The first experiment to study the effectiveness of treatment of colibacillosis pigs held in the SHA "homeland" Rossosh district of the Voronezh region from February to March 2006, the second in the SHA "Alexander" Rossosh district of the Voronezh region from February to March 2007 and the third experiment in the SHA name Dokuchaev overnight district of Voronezh region from September to November 2007

The results of the experiments are presented in tables 7-9.

Table 7
The effectiveness of the treatment of colibacillosis in pigs in the SHA "homeland" Rossosh RA is she Voronezh region
IndicatorsThe group of animals
ControlExperience
The number of animal heads7481
Recovered heads6273
%is 83.890,1
Palo goals1-
%1,3-
Left sick, goals118
%14,99,9
Recovery time, days4,7±0,33,7±0,2
Therapeutic effectiveness, %is 83.890,1

Table 8
The effectiveness of the treatment to which bacteriosis in piglets in the SHA "Alexander" Rossosh district of Voronezh region
IndicatorsThe group of animals
ControlExperience
The number of animal heads7886
Recovered heads6979
%88,591,9
Palo goals--
%--
Left sick, goals97
%11,58,1
Recovery time, days4,4±0,23,6±0,3
Therapeutic effectiveness, %88,591,9

Table 9
The effectiveness of the treatment number is bacteriosis in piglets in the SHA name Dokuchaev overnight district of Voronezh region
IndicatorsThe group of animals
ControlExperience
The number of animal heads9389
Recovered heads8082
%86,0to 92.1
Palo goals--
%--
Left sick, goals137
%14,07,9
Recovery time, days4,2±0,53,4±0,4
Therapeutic effectiveness, %86,0to 92.1

Studies have shown that the drug for the treatment of colibacillosis in young farm animals has a high therapeutic effect and the activity in the treatment of colibacillosis in pigs (on average it amounted to 91.4%), which is 5.3% higher efficacy of the drug "Self granulate". Compared with control groups using the drug for the treatment of colibacillosis in young farm animals decreased recovery time average of 22.2%.

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

Under the existing regulation on medicinal products intended for treatment of animals, experimental preclinical study of the overall pharmacological activity and Toxicological properties of the drug for the treatment of colibacillosis in young farm animals.

The studies used pharmacological, Toxicological, biochemical, pathological research methods used to study drug that received approval in research practice.

The experiments were carried out on Mature conventional nonlinear heterosexual white mice weighing 20-22 g (191 goal.) and white rats weighing 200-225 g (132 Gol.), breeding vivarium national NIVI pathology, pharmacology and therapy. The animals were kept in vivarium conditions at 20-22°C and a humidity of 40-60%. Animal keeping and provision of feed corresponded to the norm of the positive requirements of the International Convention.

Determination of the parameters of the toxicity of the drug for the treatment of colibacillosis in young farm animals in the acute experiment was conducted at a single oral administration in two species of laboratory animals - white mice and white rats.

Groups of animals were formed on the principle of paired counterparts, taking into account body weight, development, and clinical status. Before the experiments, animals are kept in quarantine for 12 days, and before the introduction of the drug were not fed within 12 hours.

Observation of animals was performed continuously during the first day after the injection. In the subsequent condition of the animals were observed twice a day for 14 days. Registered General status and behavior of animals, the state of neuromuscular and autonomic functions, coat, eating food, consumption of water. Special attention was paid to the development of signs of toxicity, assessed their severity, duration, time of recovery or death.

When studying the toxicity parameters of the drug in the acute experience of the oral method of administration the drug was administered intragastrically once in doses of 8000,0 to 14000,0 mg/kg of body weight in a volume of 0.6 ml per mouse and 6.0 ml per rat (dose are the maximum allowable volume for oral administration). Higher doses for white mice and white rats in excess of 1,000 mg/kg was administered in two doses at half the dose with an interval of 2 hours.

Based on the results of toxicometric research yielded the following parameters of acute toxicity of the drug for the treatment of colibacillosis in young farm animals, which are presented in table 10.

Table 10
The parameters of acute toxicity after a single intragastric administration to laboratory animals (mg/kg)
AnimalThe toxicity parametersSLD50
MTDLD16LD50LD84LD100
White mouse8000,09206,210776,8 (9610-11900)12284,414000,0±551,1
White rat8500,08948,211134,7 (9910-12600)13321,314500,0±627,1

Clinical symptoms of acute poisoning of white mice and white rats was accompanied by a short period of excitation with increased locomotor activity by most individuals. Rats were observed aggressiveness. For a short period of excitation developed full-blown depression, the state of deep sleep, then passing into a coma. The animals did not react to light and tactile stimuli. At the time of death of the animals was noted shortness of breath and palpitations. Breathing often becomes shallow, intermittent, developed cyanosis of the skin and mucous membranes. Death usually occurred in the state of deep oppression.

The drug toxicity refers to hazard class IV - low hazardous substances [GOST 12.1.007-76].

In the chronic experience with multiple (21 days) administration of the drug in a mixture with feed at doses 225,0 (group 1); 560, 0m (group 2) and 1115,0 mg/kg (group 3) body mass (1/50, 1/20 and 1/10 LD50found in the acute experience) established that the drug does not cause significant changes in the clinical condition of the animals: behaviour, grooming, appetite, breathing rate in all animals of the experimental groups during the period of use of the drug, and within one week after the application remained within the physiological norm. Also there were no recorded cases g is Beli animals.

During the observation period the animals of the experimental groups was not marked disorders of digestion and urination. Rats experimental groups remained active, were retained reflexes.

It is established that the drug has an effect on growth rate of animals. So dose 225,0 mg/kg of the drug stimulates the growth of animals on average by 4.0%. During the course of the drug in experimental animals, which were injected drug dose 560, 0m mg/kg, did not differ from control on weight gain and in the end of the experiment statistically significant differences on this indicator was not found.

In rats, which the drug was administered mixed with feed at a dose of 1115,0 mg/kg body weight, starting from the 7th day from the start of the experiment was noted reduced weight gain compared to control, indicating a toxic effect of the drug. However, within 10 days after the last injection, the average daily weight gain of rats approaching average daily weight gain of the control animals.

The coefficients of the weight of internal organs of rats who used the drug at all tested doses was not significantly different from control (table).

Table 11
The ratio of the mass of the inner organogram during repeated use of the drug (21 day)
Internal organControlDose, mg/kg
225,0560, 0m1115,0
Light6,8±0,476,7±0,457,1±0,347,0±0,33
Heart3,7±0,153,8±0,343,6±0,323,7±0,29
Liver32,4±1,5834,2±0,8435,6±1,3435,1±1,66
Spleen3,9±0,464,1±0,433,8±0,443,7±0,29
Kidney7,4±0,587,2±0,467,6±0,847,5±0,53
The adrenal glands0,17±0,020,16±0,020,19±0,010,20±0,01

Table 12
Morphological and biochemical indices of blood of white rats during repeated use of the drug (21 day)
IndicatorsControlDose, mg/kg
225,0560, 0m1115,0
Erythrocytes, 1012/l5,9±0,486,1±0,725,6±0,545,8±0,50
Leukocytes, 109/l10,4±1,1711,3±0,9310,2±0,839,7±0,77
Hemoglobin, g/l142,6±6,97138,4±2,04131, 5mm±10,6144,5±1,33
Total protein, g/l69,1±1,0968,9±1,8371,6±1,2468,8±2,97
Albumin, g/the 34,9±1,2536,7±2,1740,8±0,6839,0±1,69
Globulins, %α5,42±0,864,78±0,814,56±0,533,17±0,22*
β15,32±1,0415,25±0,7012,97±1,0113,91±1,59
γ13,40±1,1312,60±1,8113,26±0,46was 10.82±0,52
Urea, mmol/l8,98±0,45of 8.40±1,74to 8.70±1,068,12±1,39
Glucose, mm/lto 6.88±0,346,76±0,705,22±1,086,87±0,69
General. lipids, g/l2,10±0,601,85±0,132,10±0,132,13±0,67
Cholesterol, mmol/l 2,36±0,112,7±0,272,02±0,151,94±0,60
AST, U/l97,15±8,57111,5±10,6to 102.2±5,1115,3±4,5
Alat, U/l34,5±9,1339,2±9,2039,3±11,444,4±9,18
Creatinine, m/l52,2±to 4.5248,4±6,1761,3±1,9047,4±1,01
Alkaline phosphatase, U/l222,5±22,6191,8±18,7262,8±37,3268,0±26,2
Bilirubin, m/l4,99±0,433,53±0,55to 4.38±0,846,39±0,76
* - P<0,05 - 0,001 compared to control

In the study of animal blood also no significant changes in the morphological composition of the blood and biochemical indicators in comparison with the indicator is in the blood of the animals of the control group (table).

The exceptions were the indicators of the functional state of the liver. Rise to the top border of norm in the serum amounts of bilirubin (28.1%) and the activity of Alat (28,7%) testify to the increased load on the body. However, 10 days after the last injection of the drug figures in the experimental animals was restored to physiological values.

The study resorptive actions carried out on 10 white rats and 2 rabbits by the method of cutaneous applications at single and multiple application and rubbing of the drug at concentrations of 0.5 and 1.0%. For detection of resorption of the drug from the skin of rabbits used the method with Trifanova blue, and the rat - a method of immersion of the tail in an aqueous solution of 0.5 and 1.0% concentration.

As a result of the experiments revealed no irritating effect of the drug. The animals did not develop signs of toxicity when applied to the skin. Thus, the drug does not have an irritating and skin-resorptive effect.

In the absence of irritants in drug test allergenic properties of the drug was performed by identifying itching and swelling in sensitised with this drug in animals and provoked protein-containing products within 15 days. In experiments using is about 4 rats and 2 rabbits. As a result of the research has not identified allergenic properties of the drug.

Thus, the tested drug for the treatment of colibacillosis in pigs and calves showed that he possesses a broad spectrum of antimicrobial action, a pronounced therapeutic effect colibacteriosis in piglets and calves is low toxic. The drug technologically and economically.

Drug for the treatment of colibacillosis in young farm animals containing trimethoprim, characterized in that it further comprises sulfadimezin, colistin and glucose in the following ratio, wt.%:

Sulfadimezin11,5-15
Trimethoprim2,0-3,6
Colistin2,0-3,5
Glucose100



 

Same patents:

FIELD: chemistry, biochemistry.

SUBSTANCE: invention relates to area of microbiology and biotechnology and can be applied in agriculture. Novel strain Megasphaera elsdenii is characterised by ability to utilise lactate with degree from 40% to 90% even in presence of sugars. Strain with said ability is obtained by method, which includes culturing of sample of paunch liquid. Novel strain Megasphaera elsdenii is applied in method of treatment and prevention of lactic acidosis of ruminants, in composition of veterinary preparation for treatment and prevention of said disease, in method of milk productivity increasing and in method of increasing ruminants fattening efficiency, in method of increasing growth rate and reduction of time of ruminants fattening, in method of reducing morbidity, induced by digestion disorders, and death rate among ruminants from lactic acidosis, as well as in method of increasing efficiency of conversion of ruminants diet based on concentrated forages when transferring ruminant to said diet.

EFFECT: obtaining ability to carry out wide-scale treatment and prevention of lactic acidosis.

17 cl, 3 dwg, 18 tbl

FIELD: medicine.

SUBSTANCE: invention relates medicine area, in particular, gastroenterology, and concerns treatment of GI tract dysbacteriosis. A set containing agents, possessing antagonist action on a GI tract pathogenic microflora and agents for restoration of a normal GI tract microflora (eubiotics and bacteritic preparations), and also independent GI tract electrostimulators are used for this purpose. The method of GI tract dysbacteriosis treatment combines a diet, the specified agents, and also electrostimulator insertion before and-or in the course of treatment.

EFFECT: optimum conditions for effect of eubiotics and bacteritic preparations at the expense of preliminary normalisation of GE tract motor and evacuation functions.

2 cl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I), their optically active stereoisomers, as well as to pharmaceutically acceptable salts possessing properties of ORL1 and µ-opiate receptors. In general formula , R1 represents H, alkyl(1-6C), []m represents-(CH2)m-, in which m equals 0 or 1, R2 represents halogen, CF3, alkyl(1-6C), phenyl, cyano, cyanoalkyl(1-3C), hydroxy, (1-3C)alkoxy, OCF3, acyl(2-7C), trifluoroacetyl, (1-3C)alkylsulfonyl or trifluoromethylsulfonyl, and n represents integer number 0-4 on condition that when n equals 2, 3 or 4, R2 substituents can be similar or different, A represents saturated ring, []0 and []p represents -(CH2)o and -(CH2)p, and o and p independently correspond to 0, 1 or 2, R3, R4, R5 and R6 independently represent hydrogen, alkyl(1-3C), or (R4 and R6) together can form alkylene bridge, containing 1-3 carbon atoms on condition that when o equals 2, R3 represents hydrogen, and when p equals 2, R5 represents hydrogen, R7 represents H, halogen, alkyl(1-6C). Invention also relates to pharmaceutical composition, intermediate compounds for obtaining formula (1) compounds.

EFFECT: compounds can be used for preparing medication for treating disorders and diseases such as alimentary behaviour disturbances, arterial hypertension.

8 cl, 3 dwg, 1 tbl, 45 ex

FIELD: medicine.

SUBSTANCE: invention concerns experimental medicine and can be used in veterinary science. The Ultrasorb preparation is fed to the animals that are on a vivarium standard diet, within 14 days, based on 3 g/day, admixed with forage. The way prevents development of intestinal dysbacteriosis at animals.

EFFECT: prevention of intestinal dysbacteriosis at animals.

3 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: 24 hours prior to the examination, children aged 3 to 8 year old takes in 100 ml lactulose (Duphalac) with water of room temperature in amount 1-1.5 liters within 4-6 hours. The second dose lactulose (Duphalac) 100 ml follows with water of room temperature in amount 1-1.5 liters. To prevent overaerogenesis and to reduce discomfort, Espumisan (Simethicone) is prescribed in dosage 15 ml 3 times a day. For children aged 8 to 18 years old, there is prescribed 200 ml lactulose (Duphalac) with water of room temperature in amount 1.5-2.0 litres within 4-6 hours followed with the second dose of lactulose (Duphalac) 200 ml with water of room temperature in amount 1-1.5 litres. Additionally Espumisan (Simethicone) is introduced in dosage 15 ml 3 times a day or 3-6 capsules 3 times a day.

EFFECT: effective cleansing of gastrointestinal tract in children of different age, thus ensuring good visualisation of large intestine mucosa and decreasing drug load on organism of younger children, preserving normal microflora of large intestine and preventing overaerogenesis.

2 ex

FIELD: medicine.

SUBSTANCE: there is prescribed gluten-free diet with eliminating cereals and additional order of protein: meat 100.0 g, cottage cheese 100.0 g, or sour cream 100.0 g daily. Creon is dosed 10000 ME at mealtime within 2 weeks. It is combined with physiotherapy exercises (PTE) within 20-30 minutes. During afternoon, every second day circular douche is applied at pressure 1.5-2 atmospheres, water temperature 36-35°C for 3-4 minutes within therapeutic course 10-12 procedures. On another days, radon baths are taken at water temperature 36°C, dosed 0.75 kBq/l for 8-10 minutes within therapeutic course 8-10 procedures. Electrophoresis is applied daily with 50% Dimexide solution (±) for small intestine projection by transverse technique, current density 0.05 mA/cm2 within 12-15 minutes within therapeutic course 10-12. The BAPs VC-20, VC-22, E-36, Gi-4 are exposed to red and infrared light daily within 1.5-2 minutes per each point within therapeutic course 10-12 procedures.

EFFECT: reduced specific immunologic markers of autoimmune intestine inflammations and cytokine generation level, normalised immune response of an organism, normalised hormonal and exchange processes.

2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention relates to experimental medicine and concerns pyelonephritis prevention in experiment. During 10 days preparation "Ultrasorb" is introduced to experimental animals with food in terms of 3 g/day. Then pyelonephritis is modelled by rectal infection with uropathogenic strain of lactose-negative E.Coli at the background of cold stress.

EFFECT: absence or reliable reduction of kidney tissue inflammation in animals which obtained "Ultrasorb".

4 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to pediatrics and gastroenterology and can be used for treating intestine disbacteriosis in children less than 1 year old. For this purpose bifidumbacterin forte is introduced. First 2-3 days preparation is introduced by 25-30 doses per day in 4 takings. During next 3-4 weeks bifidumbacterin forte is introduced by 5 doses 2 times a day.

EFFECT: method allows increasing efficiency of treatment of disbacteriosis in children less than 1 year old due to application of definite scheme of preparation introduction first in optimally high dose mode, then in supporting doses.

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to gastroenterology, and applies to treatment of chronic duodenal obstruction. For this purpose erithromicin is introduced on account of 3.0 mg/kg of body weight 3 times a day. Additionally Alfadol-Ca is introduced in case of initial normocalcemia in dose 1 capsule 1 time a day. In case of initial hypocalcemia Alfadol-Ca dose is 1 capsule 2 times a day. Course of treatment is 3 months.

EFFECT: method ensures elimination of symptoms of chronic duodenal obstruction in patients with functional form of chronic duodenal obstruction in combination with syndrome of disturbed absorption and normalisation of calcium balance in organism.

2 dwg, 1 tbl, 2 ex

FIELD: medicine; gastroenterology.

SUBSTANCE: antibacterial therapy is presented with selective decontamination using antiklebsiellic bacteriophage within 10 days. After that prebiotic therapy including Hylak Forte, enzymatic agent and Linex in therapeutic dosage is combined with probiotic introduction. For dysbacteriosis of I stage Bifiform is introduced in dose 1 capsule 2 times a day, for dysbacteriosis of II and III stages dose is 2 capsules 2 times a day, combined with Lactobacterinum 5 doses once a day. Thus medicinal plant tincture is introduced including silverweed rootstock, salvia leaves, milfoil herb, St. John's wort herb, elecampane rootstock with roots, tickseed herb, mint leaves, fennel fruits and buckthorn bark at component ratio respectively 2:2:2:2:2:2:2:2:1 dosed 1\3 of glass 3 times a day, 30 min before meal, within 4 weeks.

EFFECT: method has no contraindications and provides fast normalisation of gastrointestinal tract microflora.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and aims at treatment of psoriatic skin areas, scalp or nails. It involves oral introduction 3 times a day of a composition containing about 400 mg of bosvellic acid and about 100 mkg of selenium. The acid is chosen from the group including beta-bosvellic acid, acetyl-beta-bosvellic acid, 11-keto-beta-bosvellic acid, acetyl-11-keto-beta-bosvellic acid. It is combined with local application of the composition containing about 400 mg of the specified acid.

EFFECT: offered method provides effective treatment without undesired by-effects that is ensured by developed introduction pattern of compositions based on bosvellic acid and selenium.

4 cl, 2 tbl, 2 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: invention concerns medicine and veterinary science. Said gel composition contains triptantrin, chitosan and distilled water in the ration as follows, g/l of gel: triptantrin 1.5-2.5; chitosan 15.0 25.0; distilled water - the rest.

EFFECT: extended biological action spectrum of the composition, declared composition possesses wound healing, burn-treating, antiinflammatory, hepatoprotective, antidiabetic and antineoplastic action; it is not toxic, provides higher bioavailability of triptantrin and hence, intensified physiological action thereof when transformed into bioavailable water-gel formulation.

6 tbl, 7 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: invention concerns medicine and veterinary science. Said gel composition contains triptantrin, chitosan and distilled water in the ration as follows, g/l of gel: triptantrin 1.5-2.5; chitosan 15.0 25.0; distilled water - the rest.

EFFECT: extended biological action spectrum of the composition, declared composition possesses wound healing, burn-treating, antiinflammatory, hepatoprotective, antidiabetic and antineoplastic action; it is not toxic, provides higher bioavailability of triptantrin and hence, intensified physiological action thereof when transformed into bioavailable water-gel formulation.

6 tbl, 7 ex, 4 dwg

FIELD: chemistry, biochemistry.

SUBSTANCE: invention relates to biotechnology, namely to obtaining composition of individual proteolytic ferments and can be applied in medicine, cosmetology. In contents of composition are included not less than five proteases with molecular weight from 23 to 36 kilodalton and with -N-end amino acid successions: I V G G T E V T P G E I P Y Q L S L Q D -; I V G G T E V T P G E I P Y Q L S F Q D -; I V G G Q E A S P G S W P X Q V G L F F -; I V G G S E A T S G Q F P Y Q X S F Q D -; I V G G Q E A T P H T W V H Q V A L F I -; I V G G Q E A T P H T X V H Q V A L F I -; A M D X T A Y X D Y D E I Q A X L K G L -; A F D X T N Y N T F E E I N S I L D G V -; A A I L G D E Y L X S G G V V P Y V F G - Obtained composition is applied for treatment of purulent-necrotic and cicatricial changes of tissues in contents of pharmacological composition or elimination of purulent-necrotic and cicatricial changes of tissues in contents of cosmetic composition.

EFFECT: obtaining possibility to hydrolyse protein substrates to individual amino acids, obtained substance is highly efficient and does not cause allergic reactions when applied for a long time

6 cl, 3 tbl, 4 ex

FIELD: chemistry, biochemistry.

SUBSTANCE: invention relates to area of microbiology and biotechnology and can be applied in agriculture. Novel strain Megasphaera elsdenii is characterised by ability to utilise lactate with degree from 40% to 90% even in presence of sugars. Strain with said ability is obtained by method, which includes culturing of sample of paunch liquid. Novel strain Megasphaera elsdenii is applied in method of treatment and prevention of lactic acidosis of ruminants, in composition of veterinary preparation for treatment and prevention of said disease, in method of milk productivity increasing and in method of increasing ruminants fattening efficiency, in method of increasing growth rate and reduction of time of ruminants fattening, in method of reducing morbidity, induced by digestion disorders, and death rate among ruminants from lactic acidosis, as well as in method of increasing efficiency of conversion of ruminants diet based on concentrated forages when transferring ruminant to said diet.

EFFECT: obtaining ability to carry out wide-scale treatment and prevention of lactic acidosis.

17 cl, 3 dwg, 18 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 3-aminocaprolactam of formula (I): , where X represents -CO-R1 or -SO2-R2, R1 represents alkyl (with the exception of 5-methylheptanyl and 6-methylheptanyl, where radical R1 is bonded to carbonyl in position 1), halogenalkyl, alkoxy (with the exception of tret-butyloxy), alkenyl, alkinyl or alkylamino radical from 4-20 carbon atoms (for example, from 5-20 carbon atoms, 8-20 carbon atoms, 9-20 carbon atoms, 10-18 carbon atoms, 12-18 carbon atoms, 13-18 carbon atoms, 14-18 carbon atoms, 13-17 carbon atoms) and R2 is alkyl radical from 4-20 carbon atoms (for example, from 5-20 carbon atoms, 8-20 carbon atoms, 9-20 carbon atoms, 10-18 carbon atoms, 12-18 carbon atoms, 13-18 carbon atoms, 14-18 carbon atoms, 13-17 carbon atoms); or to its pharmacologically acceptable salt. Invention also relates to application and pharmacological composition, which has anti-inflammatory activity, based on said compounds.

EFFECT: obtaining new compounds and based on them pharmacological composition, which can be applied for obtaining medications for treatment, relief or prevention of inflammatory disease symptoms.

57 cl, 62 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, photodynamic therapy, and can be used for treatment of adenoid vegetation. For this purpose 0.1% Radachlorin gel is administered into the area of adenoid vegetation on the basis of 0.2 g per 1 cm2 of a surface. In 2 hours of an exposition a surface of a nose mucous coat and adenoid vegetations are treated with laser light with 662 nanometers wavelength within 20 minutes. The dose of light energy makes 50 J/cm2. Course of treatment makes 5-8 sessions with a 2-3 days interval. The diode laser apparatus for photodynamic therapy "LAKHTA-MILON" can be used as a source of laser radiation.

EFFECT: achievement of fast and steady disappearance of inflammatory reactions, elimination of hypertrophic growth of tissues, restoration of nasal breath, prevention of postoperative complications and relapses, decrease in a dose of applied antibiotics.

2 cl, 2 ex

FIELD: medicine.

SUBSTANCE: invention concerns biotechnology. The methods of angiogenesis depression or inhibition at an individual with the pathological condition bound to an angiogenesis, providing administration of antagonist EGFL7 to an individual, capable interfering migration of endothelial cells induced by EGFL7, thereby reducing or inhibiting an angiogenesis at an individual is described. The invention can be used for regulation of the processes involved in an angiogenesis.

EFFECT: development of an effective way of depression or inhibition of an angiogenesis at an individual with the pathological condition bound to angiogenesis.

13 cl, 38 dwg, 4 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, in particular, to gastroenterology, and concerns treatment of chronic virus hepatitis B. For this purpose Roncoleukin is intravenously driply administered in a dose of 500 mg, with rate of 1-2 ml/min, during 4-6 h 2 times a week - 1 month. Then the specified preparation is administered subcutaneously, 1 ml 2 times a week within 2 months.

EFFECT: elimination of a cellular link of immunity imbalance, rapid normalisation of clinico-laboratory indicators without by-effects presentation.

2 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely gastroenterology, and is intended for treatment of ulcer in a gastro-duodenal zone. Essence of the method: the patient administers nodding catchfly or campion, dried up and crushed to 2-3 mm size of particles in a dose 0.5 g 3 times a day during food intake within 25-30 days in addition to usual medicamental ulcer therapy.

EFFECT: increase of gastro-duodenal ulcer cicatrisation rate, especially duodenum mucosa ulcer.

2 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention concerns area of medical products, in particular to structure for oral tablets with the modified release, containing fine gliclazide for depression of level of a glucose in blood with defined granulat metric structure, and also the agent modifying liberation, for gliclazide release control; and fine gliclazide for depression of level of a glucose in blood has certain profiles of dissolution in the cleared water. Besides the invention concerns the way of reception of the specified structure.

EFFECT: decrease of level of glucose in the blood during long period of time.

8 cl, 3 dwg, 9 tbl, 8 ex

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