Method of treating salmonellosis in young farm animals

FIELD: veterinary.

SUBSTANCE: invention relates to field of veterinary. Method lies in the following: as complex preparation, dioxygen is introduced intramuscularly daily two times a day in dose 0.1 ml/kg of body weight during 3-7 days. In case of serious disease course preparation is introduces 5-7 days. To calves not more than 5 ml of preparation are introduced in the same place. To piglets not more than 2.5 ml of preparation are introduced in the same place.

EFFECT: method allows to increase efficiency of treating salmonellosis in young farm animals.

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The invention relates to the field of veterinary medicine.

The damage caused by Salmonella, is the sum of the losses caused by mortality of young animals, retarded growth and development of animals recover, as well as costs connected with the organization and implementation of preventive and therapeutic measures.

Mortality in salmonellosis young reaches 40-50%. Salmonellosis are distinguished by many forms of flow, and in addition to the carriage of animals celebrate dipteridaceae colitis (diarrhea of varying degrees of severity), arthritis and pneumonia (in chronic cases), sepsis, abortion, meningoencephalitis, nutritional diseases and other less pathology. Quite often salmonellosis occurs in conjunction with other bacterial and parasitic (colibacteriosis, Pseudomonas, dysentery, pasteurellosis, diplococcus, clostridia, Bordetella, balantitis, ascariasis, trichocephalosis, cryptosporidiosis) and some other diseases [Efanova LI Diagnostics of the most widespread infectious diseases in calves and piglets.- Voronezh: the VSAU, 1995. - 128 S.; Karev EP, Soldatenko N.A., V. Zimin. Features of epidemiology of salmonellosis swine. // Environmental aspects of the epizootiology and pathology of animals, Voronezh, 1999, P.472-474].

When salmonellosis in calves and piglets as a specific therapy using a polyvalent antitox the practical serum against escherichiosis calves, pigs, lambs, sheep and poultry [Kurylenko A.N. Infectious diseases of young farm animals. / Anguilera, Volkswalk. - M.: Kolos, 2001. - P.46-47].

But at the same time, it is believed that immunization and obsecenities measures are not determinants of the incidence, because does not fully break epizootic chain. Often vaccination provides only a prerequisite for the elimination of infectious diseases. Elimination of the disease is associated with the identification and neutralization of the source of the pathogen and its transmission.

Therefore, special importance is the use of antibacterial drugs in the complex struggle with salmonellosis. The complex of therapeutic measures should include the use of antibacterial drugs with the obligatory indication of sensitivity to them microflora, as in the case of faulty and uncontrolled use of these drugs is the formation of resistant strains of microorganisms.

In the literature there are reports of high therapeutic efficacy of remission and sulfatrim from 94,2 up to 98%. Positive results in the treatment of calves gentamicin sulfate, which is administered intramuscularly 0.08 g, 2 times a day for 5 days. Recommended comprehensive neomitsinovoy and polymyxine drugs.

A number of authors reported h is stateliest Salmonella, isolated from various animal species to ampicillin and other antibiotics of a number of semi-synthetic penicillins.

One of the effective drugs nitrofuranovye number in the treatment of Salmonella pneumonia are personal and furcron [Foremen YU.N., Shahs A.G., Sosnina LU Therapeutic efficacy of furcron for respiratory diseases of pigs bacterial etiology. // Environmental aspects of the epizootiology and pathology of animals, Voronezh, 1999, S-479], used at a dose of 30 mg/kg, twice a day during 10 days.

To combat multidrug-resistant bacteria are recommended combinations of antimicrobial agents.

Known analog - drug "Diary for the treatment and prevention of gastrointestinal diseases of young animals, which contains, wt%: dioxidine 0.6 to 0.9, 40%lactic acid 10,0-15,0, methyluracil 0.6 to 0.9, the water is boiled - rest [EN 2105548 C1, 27.02.1998].

It is known for the treatment of gastrointestinal diseases of young farm animals "Diacetin"containing antibacterial dioxidine, anti-inflammatory and antipyretic agent is acetylsalicylic acid, immunomodulatory agent thymalin and natural zeolites in the following ratio, wt.%: dioxidine - 2,5-5,0, acetylsalicylic acid - 25,0-75,0, thymalin - 0,5-0,75, zeolites up to 100 [EN 2075972 C1, 27.03.1997].

WPI the walls similar - drug enroxil 5% solution for injection, representing a transparent yellow solution, 1 ml contains 50 mg of enrofloxacin [Veterinary drugs in Russia: a Reference book in 2 volumes. Vol. 1. / Irakleiou, Clallam, Nuarimol, Youripod. - M.: Selhozizdat, 2004. - S.226].

However, the use of these drugs does not always lead to positive results. On the one hand, apparently, is connected with the development of resistance of the disease to drugs. On the other hand, pharmacodynamic spectrum of changes, of course, is more pronounced when parenteral routes of administration, and drugs "Diary and Diacetin use sick animals with food or water.

Known similar gentamicin sulfate 4% is a mixture of several antibiotics produced by Micromonospora purpurea. Available in the form of a sterile solution with a content of 40 mg of the active substance in 1 ml In the treatment of colibacillosis in cattle and pigs solution of gentamicin sulfate 4% applied intramuscularly twice a day with an interval of 10-12 hours, respectively, at doses of 3.0 and 4.0 mg/kg of body weight [Veterinary drugs in Russia: a Reference book in 2 volumes. Vol. 1. / Irakleiou, Clallam, Nuarimol, Youripod. - M.: Selhozizdat, 2004. With 168-169].

Famous drug is not always effective enough and does not full the mu cure all the sick pigs, if you are having side effect (nephro - and ototoxicity).

Prototype liodice - complex preparation containing as active ingredients chloramphenicol (20 mg/ml) and dioxidine (10 mg/ml) based on polymers [Veterinary drugs in Russia: a Reference book in 2 volumes. Vol. 1. / Irakleiou, Clallam, Nuarimol, Youripod. - M.: Selhozizdat, 2004. - S].

The content of active substances and the rate of application of known drug does not allow to hold the required therapeutic concentration of antibiotics in the blood, which reduces the effectiveness of treatment.

The technical result of the invention is the improved treatment of salmonellosis in young farm animals.

The technical result is achieved by using a method for the treatment of salmonellosis in young farm animals, which is applied drug dioxygen.

Dioxygen new antibacterial combination drug on the basis of gentamicin sulfate and dioksidina [shahs A.G. and other antimicrobial activity of complex drug dioxygen. // The first Congress of veterinary pharmacologists Russia. Voronezh 21-23 June 2007: proceedings of the Congress. - Voronezh, 2007. - S-660].

In the dosage form simultaneously combines two bactericidal agent. This provides synergenic effect for MF is t, these drugs work in one phase of the cell growth, but in different metabolic pathways.

Based antibacterial action dioksidina lies selective suppression of DNA synthesis. In addition, the drug reduces the activity of extracellular nucleases and plasmocoagulase in microorganisms, which leads to dysfunction of the genetic apparatus of microbial cells and eventually suppresses the biosynthesis of biologically active macromolecules, which are factors of pathogenicity.

The mechanism of action of gentamicin is associated with impaired synthesis of polypeptides microbial cells in ribosomes.

The main purpose of the combined use dioksidina and gentamicin is an extension of the spectrum of antibacterial action, filling gaps in the spectrum of each of the components of the combination and the prevention of the formation of microbial resistance.

The method is as follows.

Drug dioxygen before applying heat to 37-38C. the Drug is administered intramuscularly daily twice daily at a dose of 0.1 ml/kg body weight for 3-5 days, with severe disease within 5-7 days. Calves entered in one place no more than 5 ml, the pigs are not more than 2.5 ml of the drug. With the introduction of large amounts of the dose is divided and injected in different places. With repeated injections, it is recommended to change the place injects the th.

The essence of the method is illustrated by examples.

Example 1. The effectiveness of the treatment of salmonellosis in pigs.

The study of clinical effectiveness of dioxygen was conducted in specialized farms CJSC "Krasnodon, SHA MHP "Nicholas", OJSC "agricultural company " Livny meat."

In SHA MHP "Nicholas" Anninsky district of Voronezh region experiment was conducted on 19 pigs 28-30 days of age, which were divided into 2 groups with regard to the General condition and the severity of the disease and under the same conditions and feeding.

The diagnosis of salmonellosis have established complex on the basis of clinical, pathological and bacteriological studies taking into account the epizootic situation.

Piglets of the first group (n=9) was treated with digoxigenin, second (n=10) - gentamicin sulphate 4%. Drug dioxygen before applying warmed up to 37-38C, was injected intramuscularly daily twice daily at a dose of 0.1 ml/kg body weight for 3-5 days, with severe disease within 5-7 days.

It is established that the use of drugs was provided by the recovery of all animals (table 1).

Table 1
Comparative therapeutic efficacy of dioxygen when salmonellosis is pigs
IndicatorsThe group of animals
Control (gentamicin sulfate 4%)Experienced (dioxygen)
The number of animal heads109
Recovered heads109
%100100
Palo goals00
%00
Left sick, goals00
%00
Recovery time, days5,10,24,10,2
Therapeutic effectiveness, %100100
Body weight per animal:
in the beginning of the experiment, kg5,106,16
at the end of the experience, kg7,29,0
Average daily weight gain, g210,05,4284,06,2

When the piglets, which were introduced dioxygen, was recovered on day 4, the average daily gain in weight was 284,06,2. Animals that were treated with gentamicin sulfate, were recovered on day 5 with the average daily weight gain 210,05,4.

Thus, studies have shown that the use of dioxygen pigs with Salmonella provides an earlier recovery of animals, accompanied by an increase in average daily weight gain.

Similar clinical trials dioxygen were conducted at JSC Agrofirma "Livny meat."

In the study of clinical effectiveness of dioxygen when Salmonella was selected 111 piglets 17-31 days of age, which were divided into 2 groups with regard to the General condition and the severity of the disease and under the same conditions of feeding and housing. The diagnosis of salmonellosis have established complex on the basis of clinical, pathological data and results bacteriological the study (selected serological variants of Salmonella cholerae suis, and Salmonella typhimurium).

Animals of the experimental group (n=58) was used dioxygen, and the pigs of the control group (n=53) - gentamicin sulphate 4%.

The preparations used according to the same scheme. It is established that dioxygen has a pronounced therapeutic efficacy (100%) (table 2)

Table 2
Comparative therapeutic efficacy of dioxygen in salmonellosis pigs
IndicatorsThe group of animals
Control (gentamicin sulfate 4%)Experienced (dioxygen)
The number of animal heads5358
Recovered heads5158
%96,2100
Palo goals20
%the 3.80
Left sick, goals0 0
%00
Recovery time, days5,10,34,00,2
Average daily gain in live weight, g96,011,2to 115.514,5
Therapeutic effectiveness, %96,2100

While the animals of the experimental group was well on the 4th day, the average daily gain in weight amounted to 115.514,5, control recovered 96,2% of the animals, and recovery occurred on the 5th day, the average daily gain in weight was 96,011,2 that 19.8% lower than that of the experimental animals.

Example 2. The effectiveness of the treatment of salmonellosis in calves.

To study the efficacy of treatment of salmonellosis in calves conducted four experiments on calves 30-40 days of age weighing 50,0-70,0 kg and 2-2 .5 months of age.

According to the principle of paired analogues animals were divided into two groups. The diagnosis of the disease salmonellosis has established a comprehensive manner on the basis of the clinical examination of animals, laboratory investigations, conducting autopsies, taking into account the epizootic situation in the farms is.

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

In three experiments calves of the control group was treated with a solution of gentamicin sulfate 4%, which was administered intramuscularly at a dose of 3 mg/kg body weight twice a day for 3-5 days. In the fourth experience calves of the control group was treated with enroxil 5% production company KRKA (Slovenia) [Veterinary drugs in Russia: a Reference book in 2 volumes. T.1. / Irakleiou, Clallam, Nuarimol, Youripod. - M.: Selhozizdat, 2004. - S.226], which was administered subcutaneously at a dose of 1 ml/20 kg body weight of 1 times a day for 3-5 days.

Animals of the experimental group for the treatment of used dioxygen daily intramuscularly twice daily at a dose of 0.1 ml/kg body weight for 3-5 days, with severe disease within 5-7 days.

The first experiment to study the effectiveness of dioxygen for the treatment of salmonellosis calves held in LLC Storozhevsky" Ostrogozhsk district of the Voronezh region in March-may 2004. The second experiment was conducted in SHPK "Telegence" Lipetsk region Lipetsk region in April-may 2004. The third experiment was conducted in LLC Storozhevsky" Ostrogozhsk district of the Voronezh region in March-April 2005. The fourth experiment to study the effectiveness of dioxygen for the treatment of Salmonella is for calves held in a SEC "Starosolszky" Khokholskiy district of Voronezh region in February 2007.

The results of experiments to study the effectiveness of dioxygen for the treatment of salmonellosis in calves are presented in tables 3-6.

Table 3
The effectiveness of dioxygen for the treatment of salmonellosis in calves LLC Storozhevsky" Ostrogozhsk district of Voronezh oblast
IndicatorsThe group of animals
ControlExperience
The number of animal heads
Recovered heads
%
Palo goals
%
Left sick, goals
%
Recovery time, days
Therapeutic effectiveness, %
90
76
84,4
4
4,4
10
11,1
4,90,5
84,4
95
90
94,7
1
1,1
4
4.2V
3,70,5
94,7
Table 4
The effectiveness of dioxygen for the treatment of salmonellosis in calves in SHPK "Telegence" Lipetsk region Lipetsk region
Indicators The group of animals
ControlExperience
The number of animal heads
Recovered heads
%
Palo goals
%
Left sick, goals
%
Recovery time, days
Therapeutic effectiveness, %
65
52
80,0
6
9,2
7
10,8
5,30,5
80,0
73
66
90,4
2
2,7
5
6,9
4,00,4
90,4

Table 5
The effectiveness of dioxygen for the treatment of salmonellosis in calves LLC Storozhevsky" Ostrogozhsk district of Voronezh oblast
IndicatorsThe group of animals
ControlExperience
The number of animal heads
Recovered heads
%
Palo goals
%
Left sick, goals
%
Recovery time, days
Therapeutic effectiveness, %
69
58
84,1
3
4,3
8
11,6
5,30,5
84,1
73
67
91,8
2
2,7
4
5,5
4,90,5
91,8
Table 6
The effectiveness of dioxygen for the treatment of salmonellosis in calves in SEC "Starosolszky" Khokholskiy district of Voronezh region
IndicatorsThe group of animals
ControlExperience
The number of animal heads
Recovered heads
%
Palo goals
%
Left sick, goals
%
Recovery time, days
Therapeutic effectiveness, %
26
22
84,6
0
0
4
15,4
9,00,2
84,6
23
22
95,7
0
0
1
4,3
7,10,1
95,7

Studies have shown that dioxygen has a high therapeutic efficacy in the treatment of salmonellosis in calves. In all experiments, the use of dioxygen were lower compared with the control timing recovery (average of 20.0%), mortality (average 2.9%). therapeutic efficacy of dioxygen above Comparators on average by 9.9%.

Thus, the tested drug for the treatment of salmonellas in piglets and calves showed that he possesses a broad spectrum of antimicrobial action, a pronounced therapeutic effect in cases of salmonellosis in the irrigated and calves. The drug technologically and economically.

1. Treatment of salmonellosis in young farm animals, including the introduction of the integrated product, characterized in that as a complex of the drug to enter dioxygen daily intramuscularly twice daily at a dose of 0.1 ml/kg of body weight within 3-7 days.

2. The method according to claim 1, characterized in that in severe disease the drug is administered for 5-7 days.

3. The method according to claim 1, characterized in that the calves injected in one place no more than 5 ml

4. The method according to claim 1, characterized in that the piglets injected in one place is not more than 2.5 ml of the drug.



 

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6 tbl, 6 ex

FIELD: medicine; neurology.

SUBSTANCE: invention concerns treatment methods for neurodegenerative brain condition, such as Parkinson' and Alzheimer's disease, and methods of nerve cells death and degeneration. A therapeutically effective quantity of the composition containing brimonidin or its pharmaceutically acceptable salt is administered to a mammal.

EFFECT: treatment or prevention of nerve cells degeneration due to neuroprotective effect of brimonidin in respect of brain neurons.

6 cl, 1 ex, 1 dwg, 2 tbl

FIELD: organic synthesis.

SUBSTANCE: invention provides compounds of general formula I:

, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.

EFFECT: increased choice of cysteine protease inhibitors.

34 cl, 1 tbl, 13 ex

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