RU2367433C1 - Preparation for mastitis treatment in lactating cows - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: said preparation contains the components as follows, %: Lincomycin hydrochloride 2.0-4.0; Dioxidine 0.5-1.0; soft Monoglyceride 3.0; distilled Monoglyceride 3.0; Vaseline oil to 100. The preparation is applied to treat all forms of mastitis in lactating period. Prior to introduction thereof, udder secretion is milked dry from an affected portion and utilised; a dug is disinfected. Before use, the contents of a syrette or a bottle is heated up to 37°C, agitated thoroughly to a uniform suspension, a sterile syringe is filled with 10 ml thereof from the bottle. The syringe or the syrette is tightly pressed to outer orifice of teat canal. The preparation is introduced therein by careful pressing the syringe piston. After introduction, gentle massage of the affected dug follows bottom-up. Considering the severity of inflammatory process, the preparation is introduced in a dose 10 ml once a day (preferentially, after afternoon milking) every 24 hours to ensure complete recovery of the affected dug portion. (2-4 times).

EFFECT: improved therapeutic effectiveness.

9 tbl, 5 ex

Description

The invention relates to the field of veterinary medicine, in particular to drugs for the treatment of mastitis in cows during lactation.

Mastitis is an inflammation of the mammary gland that occurs in response to the effects of adverse mechanical, physical, chemical and biological factors.

The main factors contributing to the emergence and development of mastitis are the technical imperfection of milking machines, violation of the technology and rules of machine milking of cows. In the beginning, irritation occurs, which, when repeated, passes into aseptic inflammation - latent mastitis. The general and local (udder) resistance decreases, conditions are created for the penetration and reproduction of various conditionally pathogenic and pathogenic microflora, which causes inflammation of various forms from subclinical, occurring independently during one or two lactations and leading to atrophy, or transforming into clinically expressed ( serous, catarrhal) mastitis, etc.

Diseases of the mammary gland of cows are widespread and cause great economic damage to livestock farming, amounting to hundreds of millions of rubles. It consists of milk shortage, premature culling of cows, high incidence of young animals. All this violates the rhythmic flow production of milk, reduces the production and economic efficiency of dairy cattle breeding, which negatively affects the provision of dairy products to the country's population. Therefore, the development of new highly effective means, methods of treatment and prevention of mastitis in cows is of current importance.

Currently, domestic and foreign manufacturers produce drugs for the treatment of cows with mastitis, including antibiotics, sulfonamide, nitrofuran and other drugs. But not all of them give the desired effect, which is primarily due to a decrease in sensitivity to these microflora, which causes mastitis. In this regard, there is a need to create new complex preparations with a wide spectrum of action.

As an analogue to the proposed drug, we took Mastisan A, recommended for the treatment of mastitis in animals, containing potassium or sodium salt of benzylpenicillin, streptomycin, norsulfazole or sulfadimesin suspended in vegetable oil, in the following ratio of components, ED and g / ml:

Sodium or potassium salt of benzylpenicillin - 20,000 IU / ml

Streptomycin sulfate - 20,000 IU / ml

Norsulfazole or sulfadimesin - 0.004 g / ml

Oil base up to 1 ml

The dose of administration is 5-20 ml in the nipple cistern of the udder with an interval of 24 hours until complete cure [Veterinary preparations of Russia. Directory. M., 2004. Part 1. - S. 469].

Known drug Mastisan B, containing in its composition:

Neomycin Sulfate - 250 PIECES / ml

Sulfadimezin - 0.0035 g / ml

Methyluracil - 0.0035 g / ml

Oil base up to 1 ml

[Antibiotics, sulfonamides and nitrofurans in veterinary medicine: Reference book / V.F. Kovalev, I.B. Violin and others - M .: Agropromizdat, 1988. - P.124].

Known drug Mastisan E, containing in its composition:

Erythromycin 11250 IU / ml

Sulfadimezin - 0.004 g / ml

Oil base up to 1 ml

[Veterinary preparations of Russia. Directory. M., 2004. Part 1. - S. 469].

Known drug dienomast. Dienomast is a complex preparation containing gentamicin sulfate (2000 μg / g), dioxidine (1000 μg / g), beeswax and liquid paraffin [Veterinary preparations of Russia. Directory. M., 2004. Part 1. - S. 461].

A common disadvantage of known drugs is low therapeutic efficacy, as with the repeated use of antibiotic-containing drugs, the formation of resistance (resistance) of microorganisms to them was noted. Most preparations produced in the form of suspensions exfoliate during storage, and vegetable oils are oxidized.

The prototype of the invention is a drug for the treatment of mastitis in cows during lactation, consisting of the following components (g in 100 ml): neomycin sulfate - 2, lincomycin hydrochloride - 2, soft monoglyceride - 3, distilled monoglyceride - 3, oil - up to 100 [RU , 2180559, C1, 04/18/2002].

This drug is not effective enough, because the combination of antimicrobial agents of this drug provides only an additive effect.

The technical result of the invention is an increase in therapeutic efficacy.

The technical result is achieved through the use of lincomycin hydrochloride as a broad-spectrum antibiotic and dioxidine, effective in infections that are difficult to treat with other antimicrobial agents, in the form of a stable suspension in an oil base that does not irritate the udder tissue.

Compared with the prototype drug, the essential distinguishing features of the present invention are the signs characterizing the introduction of a broad-spectrum antibiotic, lincomycin hydrochloride and a chemotherapeutic agent, dioxidine, effective in case of insufficient activity of other antibiotics. As emulsifiers, the preparation is based on mild monoglyceride and distilled monoglyceride in an effective amount.

The drug for the treatment of mastitis in cows during lactation consists of the following components:

Lincomycin hydrochloride - 2.0-4.0%

Dioxidine - 0.5-1.0%

Soft monoglyceride - 3.0%

Distilled monoglyceride - 3.0%

Vaseline oil - up to 100%.

The achievement of the technical result from the use of the proposed preparation is explained by the fact that lincomycin hydrochloride, which is part of the medicinal product, is effective against most gram-positive cocciform (staphylococci, streptococci, pneumococci) and some gram-positive rod-shaped microorganisms, mycoplasmas and bacteria resistant to other antibiotics. Lincomycin inhibits protein synthesis in a microbial cell by interacting with SOS - ribosome subunits. It blocks the formation of polysomal functional complexes and the translation of amino acids associated with RNA transport [Navashin S.M., Fomina I.P. Rational antibiotic therapy. M., "Medicine", 1982, p.146-149]. The dioxidine included in the preparation belongs to the quinoxaline series - 1,4-di-N-oxide-2,3-di (oxymethyl), quinoxaline exhibits high antimicrobial activity against gram-negative and gram-positive microorganisms. Gram-negative microorganisms are most affected by dioxidine [“Temporary instruction on the use of dioxidine in veterinary medicine”. Approved General Directorate of Veterinary Medicine November 5, 1991].

The monoglycerides introduced into the preparation are used as emulsifiers and stabilizers of edible fats, cosmetic creams, pharmaceutical ointments, plasticizers [Chemical Encyclopedia. M .: Publishing. “Owls. Encyclopedia ”, 1989, vol. 1, p. 584-585].

The inventive drug is used during lactation to treat all forms of mastitis. Before the introduction of the drug, the secretion of the udder is extruded from the affected lobe and disposed of, the nipple is disinfected. The contents of the syringe of the tube or vial are heated to 37 ° C before use, shaken thoroughly until a uniform suspension is obtained, 10 ml are taken from the vial into a sterile syringe. The syringe or syringe tube is tightly pressed to the outer opening of the nipple canal, the drug is injected into the nipple cistern by carefully pressing the syringe plunger. After the introduction, a light massage of the nipple of the affected lobe of the udder is conducted from the bottom up. Depending on the severity of the inflammatory process, the drug is administered in a dose of 10 ml once a day (preferably after evening milking) with an interval of 24 hours until the affected portion of the udder is completely cured (2-4 times).

During treatment and within 3 days after the last administration of the drug, milk from the affected udder lobes is dispensed into a separate bowl, neutralized and disposed of, and the animals are fed from the remaining udder lobes after boiling.

To obtain a dispersed medium, 6.0% of monoglycerides are dissolved at a temperature of 80 ° C in liquid paraffin, added up to 100%. The mixture is autoclaved at a temperature of 120 ° C for 1.5-2 hours. A portion of powders is added to a base cooled to a temperature of 30-35 ° C: lincomycin hydrochloride 2-4% and dioxidine 0.5-1%, previously crushed in a ball mill, include a stirrer for 15-20 minutes and packaged.

In appearance, the drug is a stable oily suspension of a viscous consistency with a specific odor, light yellow in color with a greenish tint. At a temperature of 35 ° C, the suspension has a liquid consistency. The drug completely retains its original properties (appearance, color, authenticity, mass fraction of dioxidine, mass fraction of lincomycin hydrochloride, microbial purity, mechanical inclusions) and does not stratify for 12 months of storage at a temperature of 0 to 25 ° С.

The use of milk for human consumption is allowed 72 hours after the last injection, provided that the clinical signs of mastitis disappear completely. Slaughter of animals for meat is allowed no earlier than 7 days after the last injection of the drug. Meat of animals forced to be killed earlier than this period can be used for the production of meat and bone meal or for feed to fur animals.

The effectiveness of the drug was tested on cows belonging to Dolzhanskoye CJSC of the Veideleevsky District of the Belgorod Region, Manino CJSC to the Kalachaevsky District of the Voronezh Region, Uspenskoye AONN and Zdorovetsky SEC of the Livensky District of the Oryol Region. The essence of the technical solution is illustrated by examples.

Example 1

In order to verify the effectiveness of the prototype of the invention, the antimicrobial activity of lincomycin, neomycin and their combination against the main causative agents of mastitis was studied. The results are presented in table 1.

Table 1 Antimicrobial activity of lincomycin, neomycin and their combinations in relation to the main causative agents of mastitis, μg / ml No. p / p Microbe culture Lincomycin hydrochloride Neomycin sulfate Lincomycin: neomycin 1: 1 one Staphylococcus aureus-209 P 12.5 12.5 12.5 2 Streptococcus agalactic-586 12.5 25.0 12.5 3 E. coli 0138 one hundred 12.5 25.0

A study of the antimicrobial activity of this drug and its individual components showed that the combination of antimicrobial agents of this drug provides an additive effect, i.e. the overall effect is equal to the sum of the actions of each component of them individually.

Example 2

To identify the optimal ratio of components and the effectiveness of the drug, three formulations were prepared.

Recipe No. 1: dioxidine 1.0%; lincomycin 2.0%; distilled monoglyceride 3.0%; soft monoglyceride 3.0%; Vaseline oil - up to 100%.

Recipe 2: dioxidine 0.5%; lincomycin 4.0%; distilled monoglyceride 3.0%; soft monoglyceride 3.0%; Vaseline oil - up to 100%.

Recipe 3: dioxidine 0.75%; lincomycin 3.25%; distilled monoglyceride 3.0%; soft monoglyceride 3.0%; Vaseline oil - up to 100%.

In order to determine the effectiveness of the proposed drug was selected 71 cow with subclinical mastitis, divided by the principle of analogues into four groups. Animals of the first, second and third groups were subjected to therapy with the proposed drug (various formulations) at a dose of 10 ml once a day for 2-4 days, the fourth - dienomast according to the instructions for its use. After 7-10 days, the animals were examined clinically, and milk with a 2% mastidine solution, a breakdown assay, selectively by counting the number of somatic cells.

table 2 Therapeutic efficacy in subclinical mastitis Household Treated Multiplicity of drug administration Recovery time, days Cows recovered Healed cows share qty % qty % Recipe 1 twenty 23 2.23 ± 0.1 2.5 ± 0.12 eighteen 90.0 22 95.6 Recipe 2 twenty 24 2.26 ± 0.09 2.65 ± 0.05 eighteen 90.0 21 87.5 Recipe 3 36 38 2.15 ± 0.12 2.5 ± 0.11 35 97.2 36 94.7 Dienomast 35 39 2.48 ± 0.12 2.75 ± 0.09 31 88.5 34 87.1 Table 3 Therapeutic efficacy of catarrhal mastitis in cows Household Treated Multiplicity of drug administration Recovery time, days Cows recovered Healed cows share qty % qty % Recipe 1 twenty 24 3.28 ± 0.05 3.60 ± 0.09 17 85.0 22 91.7 Recipe 2 twenty 23 3.31 ± 0.09 3.62 ± 0.11 eighteen 90.0 twenty 86.9 Recipe 3 25 28 3.22 ± 0.07 3,55 ± 0,09 23 92.0 26 92.8 Dienomast 24 29th 3.4 ± 0.05 3.85 ± 0.1 19 84.2 25 86.2

Table 4 Therapeutic efficacy of the drug in purulent catarrhal mastitis in cows Household Treated Multiplicity of drug administration Recovery time, days Cows recovered Healed cows share qty % qty % Recipe 1 10 13 4.3 ± 0.12 4.9 ± 0.11 8 80.0 eleven 84.6 Recipe 2 10 12 4.49 ± 0.12 4.87 ± 0.11 8 80.0 9 75.0 Recipe 3 22 26 4.2 ± 0.11 4.7 ± 0.11 19 86.3 23 88.5 Dienomast 21 24 4.7 ± 0.1 5.5 ± 0.12 fifteen 71,4 eighteen 75.0 Table 5 Therapeutic efficacy of cows with serous mastitis in cows Household Treated Multiplicity of drug administration Recovery time, days Cows recovered Healed cows share qty % qty % Recipe 1 10 fourteen 2.9 ± 0.11 3.61 ± 0.009 8 80.0 eleven 78.6 Recipe 2 10 16 3.1 ± 0.11 3.69 ± 0.01 8 80.0 13 81.3 Recipe 3 21 27 2.88 ± 0.08 3.65 ± 0.09 eighteen 85.7 22 81.5 Dienomast 21 29th 3.15 ± 0.11 3.85 ± 0.1 16 76.1 22 75.8

As can be seen from the data presented in tables 2-5, the proposed drug (formulation 1; 2; 3) has a higher therapeutic effect in comparison with dienomast. The proposed therapeutic formulation No. 3 has the highest therapeutic effect; its effectiveness in case of subclinical mastitis was 97.2%, catarrhal - 92.0%; purulent-catarrhal - 86.3%; serous - 85.7%, which is 8.7; 7.0; 9.6; 14.9 and 9.6% higher than with dienomast treatment.

Thus, a high therapeutic effect was achieved when using the following composition of the drug for the treatment of mastitis in cows during lactation: dioxidine 0.75%; lincomycin 3.25%; distilled monoglyceride 3.0%; soft monoglyceride 3.0%; Vaseline oil - up to 100%.

Example 3

The effect of the drug (dioxidine 0.75%; lincomycin 3.25%; distilled monoglyceride 3.0%; soft monoglyceride 3.0%; liquid paraffin - up to 100%) for the treatment of mastitis in cows on the mammary gland and the body of lactating cows were studied three clinically healthy animals at 3-4 months of lactation by intracisternal administration of the drug, heated to 37 ° C, at a dose of 10 ml in the left front lobe of the udder, and the right front lobe served as a control. After 3; 6; 12; 48 and 72 hours after administration of the drug, the cows were clinically examined, and milk samples were taken from these quarters of the udder to evaluate the reaction with a 2% mastidine solution, determine the number of somatic cells (SC) and set up a sedimentation sample.

The research results are shown in tables 6 and 7.

Table 7 The effect of intracisternal administration of a drug for the treatment of mastitis in cows during lactation on indicators of the general condition of the body Study time, hour Indicators T ° C Pulse The number of breathing. movements in 1 min Quantity abbr. scar in 5 min Before introduction 38.1 ± 1.3 70.7 ± 0.78 17.0 ± 0.54 5.7 ± 0.19 In: 3 38.1 ± 0.16 71.0 ± 0.09 17.0 ± 0.54 5.3 ± 0.19 6 38.2 ± 0.12 71.3 ± 1.56 17.3 ± 0.19 5.7 ± 0.19 12 38.0 ± 0.12 72.3 ± 1.56 18.0 ± 0.39 6.7 ± 0.19 24 38.1 ± 0.08 75.3 ± 1.56 18.0 ± 0.39 6.7 ± 0.19 48 38.1 ± 0.08 75.3 ± 0.39 18.7 ± 0.39 6.0 ± 0.39 72 38.2 ± 0.16 76.3 ± 0.98 18.7 ± 0.19 6.0 ± 0.39

It was found that after intracisternal administration of a drug for the treatment of mastitis in cows during lactation at a dose of 10 ml, the number of somatic cells increases (table 6) after 3 hours 1.45 times (from 316.6 ± 17.1 to 459.8 ± 13.9 thousand / ml), after 6 hours - at 2.57; after 12 hours - 3.9; after 24 hours - at 4.98; after 48 hours - 2.22 times and by 72 hours - it approaches the initial level (368.9 ± 30.4 thousand / ml). In this case, the reaction of the secretion of the udder with a 2% solution of mastidine for 48 hours was positive, and the assay sample was negative. After intracisternal administration of the drug, no noticeable changes were found in the general condition of the animal organism.

Thus, the drug for the treatment of mastitis during lactation has a moderate irritating effect on the mammary gland of cows, the signs of which disappear after 72 hours after administration, and can be recommended for intracisternal administration in order to treat mastitis in cows.

Example 4

The study of the antimicrobial action of the drug for the treatment of mastitis in cows during lactation (dioxidine 0.75%; lincomycin 3.25%; distilled monoglyceride 3.0%; mild monoglyceride 3.0%; liquid paraffin - up to 100%) and its components serial dilution method in a liquid nutrient medium. For the experiments, pathogenic microbial cultures were used, isolated from the secret of mastitis patients with cows, as well as museum strains.

Data on the determination of antimicrobial activity are shown in table 8.

Table 8 Antimicrobial activity of the drug for the treatment of mastitis in cows and its components in relation to the main causative agents of mastitis, MIC, μg / ml No. p / p Microbe culture Lincomycin Dioxidine The drug for the treatment of mastitis in cows one Staphylococcus aureus-209 P 12.5 25.0 6.3 2 Staphylococcus aureus-589 6.3 25.0 3,1 3 Streptococcus agalactic-586 12.5 12.5 6.3 four Streptococcus agalactic-587 25.0 25.0 3,1 5 Streptococcus agalactic-588 25.0 50,0 3,1 6 Streptococcus gr. D-640 one hundred 50,0 25.0 7 Escherichia coli 643 one hundred 50,0 25.0

As can be seen from the data presented, the combination of dioxidine in a ratio of 1: 4 has a wide spectrum and high antimicrobial activity against the main causative agents of mastitis at a concentration of 3.1-25.0 μg / ml, which exceeds the antimicrobial activity of dioxidine and lincomycin separately in 2- 16 times.

When studying the antibacterial effect of the combination of lincomycin and dioxidine in in vitro experiments, we found that the minimum inhibitory concentration of each of the antibiotics in the presence of the other decreases significantly. For example, in the presence of lincomycin hydrochloride at a concentration of 2.51-5.12 μg / ml, the minimum inhibitory concentration (MIC) of dioxidine in relation to Staphylococcus aureus-209P and Staphylococcus aureus-586 decreases to 0.59-1.18 μg / ml (in 21.2 times). Conversely, the presence in the combination of dioxidine at a concentration of 1.18 μg / ml reduces the BMD of lincomycin to 5.12 μg / ml (2.44 times).

When lincomycin hydrochloride is added to dioxidine at a concentration of 2.51-5.12 μg / ml, the MPC of the first against agalactic streptococcus (strains 586; 587; 588) decreases to 0.59-1.18 (in 21.0-84.7 times). At the same time, the presence of dioxidine at a concentration of 0.59-1.18 μg / ml in relation to this microorganism reduces the BMD of lincomycin to 2.51-5.12 μg / ml (2.44-9.9 times).

In relation to Escherichia coli 643 and group D streptococcus, in the presence of lincomycin at a concentration of 4.9 μg / ml, the IPC of dioxidine decreases to 10.6 μg / ml (4.9 times), and the presence of dioxidine at a concentration of 10.6 μg / ml in relation to these microorganisms reduces the BMD of lincomycin hydrochloride to 4.9 μg / ml (10.6 times).

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

Dioxidin exhibits high antimicrobial activity against gram-negative and gram-positive microorganisms. Gram-negative microorganisms are most affected by dioxidine [Temporary guidance on the use of dioxidine in veterinary medicine. Approved General Directorate of Veterinary Medicine November 5, 1991]. The antibacterial action of dioxidine is based on the selective suppression of DNA synthesis. In addition, the drug reduces the activity of extracellular nuclease and plasmocoagulase in microorganisms, which leads to dysfunction of the genetic apparatus of the microbial cell and, as a result, the synthesis of biologically active macromolecules, which are pathogenicity factors, is suppressed.

Lincomycin is effective against most gram-positive coccoid (staphylococci, streptococci, pneumococci) and some gram-positive rod-shaped microorganisms, mycoplasmas and bacteria that are resistant to other antibiotics. Lincomycin inhibits protein synthesis in a microbial cell by interacting with SOS - ribosome subunits. It blocks the formation of polysomal functional complexes and the translation of amino acids associated with RNA transport [Navashin S.M., Fomina I.P. Rational antibiotic therapy. M., "Medicine", 1982, p.146-149].

Example 5

In the production environment it is shown (table 9) that the proposed drug in the aggregate of lincomycin hydrochloride and dioxidine ensures the achievement of a new super-cumulative effect in comparison with one of the analogues (dienomast).

Table 9 The effectiveness of treatment of cows with various forms of mastitis Treated Multiplicity of drug administration Recovered Cured cows share cows % share % Subclinical mastitis Dienomast 76 92 2.6 ± 0.1 69 90.8 81 88.0 The drug for the treatment of mastitis in cows during lactation 79 90 2.28 ± 0.11 74 93.7 85 94.4 Catarrhal mastitis Dienomast 66 79 3.48 ± 0.13 54 81.8 65 82,2 The drug for the treatment of mastitis in cows during lactation 66 76 3.30 ± 0.07 61 92.4 69 90.8 Purulent catarrhal mastitis Dienomast 52 62 4.73 ± 0.11 38 73.1 45 72.6 The drug for the treatment of mastitis in cows during lactation 55 63 3.78 ± 0.06 47 85.5 53 84.1 Serous mastitis Dienomast 47 67 3.5 ± 0.19 36 76.6 51 76.1 The drug for the treatment of mastitis in cows during lactation 48 69 3.0 ± 0.13 40 83.3 57 82.6

Thus, the drug for the treatment of mastitis in cows during lactation has a higher therapeutic efficacy compared to the prototype, due to the use of lincomycin hydrochloride as a broad-spectrum antibiotic and dioxidine, effective in infections difficult to treat with other antimicrobial agents, in the form of stable oil-based suspensions that do not irritate breast tissue.

Claims (1)

The drug for the treatment of mastitis in cows during lactation, containing as antibiotic lincomycin hydrochloride, as emulsifiers - soft monoglyceride and distilled monoglyceride and an oil base, characterized in that it additionally contains dioxidine, and as an oil base - vaseline oil in the following ratio components,%:
Lincomycin hydrochloride 2.0-4.0 Dioxidine 0.5-1.0 Soft monoglyceride 3.0 Distilled monoglyceride 3.0 Vaseline oil up to 100