RU2180559C1 - Preparation to treat mastitis in animals - Google Patents

Abstract

FIELD: veterinary science. SUBSTANCE: the preparation in question contains, g/ml injection dose: gentamycin sulfate 0.017, dioxidine 0.01, soft monoglyceride 0.03, solid monoglyceride 0.03, oil - up to 1.0. Preparation is prepared by dispersing an antibiotic powder in an oily base (oil and emulsifiers) in a colloid grinder to obtain homogeneous and stable suspension. Curative dosage for intracisternal injection is 10 ml. As a result of a daily single usage of the mentioned preparation the recovery in animals is obtained in 1-5 d of therapy. EFFECT: higher efficiency. 14 cl, 4 tbl, 4 ex

Description

 The invention relates to agriculture, in particular to veterinary medicine, and can be used to treat mastitis in animals.

 Mastitis (Mastitis) is an inflammation of the mammary gland that develops under the influence of environmental factors, biological factors, and environmental factors (1, 2).

 Environmental factors contributing to the emergence and development of mastitis include mechanical, thermal and chemical. The main factors are technical imperfection of milking machines and violation of machine milking technology.

 Violation of optimal conditions for keeping and feeding cows also reduces their general and local (udder) resistance to mastitis.

 In clinically healthy cows in the parenchyma (alveoli) of the mammary gland, microorganisms are absent.

 In case of violation of veterinary and sanitary rules for the care of milking units and milking hygiene, as well as a decrease in the overall stability of the animal and mammary gland, colonization by the microorganisms of the nipple apex and the external opening of the nipple canal. Then microorganisms penetrate into the nipple and sucker tanks (sinuses) and cause an infectious process of varying severity from subclinical to clinically severe inflammation of various forms.

 Thus, mastitis in cows is a polyetiological disease.

 The most common causative agents of mastitis are gram-positive microorganisms (Staphylococcus aureus, Streptococcus agalactiac, etc.), as well as gram-negative (E. coli, Klebsiella, etc.) and fungi.

 By the nature of the inflammation, mastitis is divided into the following forms: latent, serous, catarrhal, hemorrhagic, fibrinous, purulent and specific. In case of violation of the technology and rules of milking, an irritation occurs at first, which turns into aseptic inflammation - latent mastitis, followed by colonization by microorganisms and the development of an infectious process of varying severity.

 Inflammation of the udder in Russia, as in many countries of the world with developed dairy cattle breeding, occupies a leading place among cow diseases and causes great economic damage. It is recorded in all herds, they suffer from 30, and in enzootic cases up to 80 percent of dairy cows. The economic damage caused by mastitis consists of losses in milk production, deterioration of the nutritional and technological properties of milk, as well as a reduction in the life of cows, incidence of calves, treatment costs and other factors. Therefore, the development of the most effective means and methods of combating mastitis in cows and their introduction into the technology of dairy cattle breeding is a great reserve in increasing livestock productivity and food quality for the population.

 In the fight against mastitis of cows, the ongoing organizational, technological and veterinary and sanitary preventive measures do not always give positive results, and therefore the role of medical work is increasing.

 Therefore, in the complex of measures to combat mastitis, the main importance is attached to the use of special anti-inflammatory drugs, which have an antibacterial effect against pathogens of the udder. Currently, domestic and foreign manufacturers produce many different drugs for the treatment of cows with mastitis.

 They differ in the spectrum of antimicrobial agents used, the basis (solvent), doses and routes of administration (3, 4).

For the treatment of mastitis, preparations containing:
1) antiseptic agents (iodine, rivanol, etc.), which are substances indiscriminate on pathogens, and
2) chemotherapeutic agents related to substances of selective action on certain types of microorganisms. This group includes: sulfa drugs, antibiotics, nitrofurans and new drugs of different groups (quinolones, quinoxaline derivatives, etc.).

 Selectivity of drugs is an effective ability to affect pathogens of only a certain family (genus), but at the same time it requires constant monitoring of microorganisms in case of inflammation of the udder and / or selection of substances with wide selectivity.

 Therefore, in the treatment of mastitis, complex and prolonged preparations containing several chemotherapeutic agents in oil, which are administered intracisternally, are more often used.

Known complex drug Mastisan A for the treatment of mastitis in animals, containing in its composition potassium or sodium salt of benzylpenicillin, streptomycin, norsulfazole or sulfadimezin suspended in vegetable oil, in the following ratio of ingredients, ED and g / ml:
Potassium or sodium salt of benzylpenicillin - 20,000 IU / ml
Streptomycin sulfate - 20,000 IU / ml
Norsulfazole or sulfadimesin - 0.04 g / ml
Oil base - Up to 1 ml
The dose of administration is 5-20 ml into the nipple cistern of the udder with an interval of 24 hours until complete cure (5).

Known drug Mastisan B for the treatment of mastitis, containing neomycin sulfate, sulfadimezin, methyluracil, liquid paraffin and polyglycerol distiarate as an oil base in the following ratio of ingredients, ED and g / ml:
Neomycin Sulfate - 250 PIECES / ml
Sulfadimezin - 0.0035 g / ml
Methyluracil - 0.0035 g / ml
Oil base - up to 1 ml (6)
Known drug Mastisan E for the treatment of mastitis in animals, containing erythromycin, sulfadimezin, polyethylsiloxane liquid (PES) with an emulsifier as an oil base in the following ratio of ingredients, ED and g / ml:
Erythromycin - 11250 IU / ml
Sulfadimesin - 0.04 g / ml
Oil base - Up to 1 ml
The dose of administration is 5-10 ml 2 times a day until recovery (7).

Known drug Masticide for the treatment of cows with mastitis, containing potassium or sodium salt of penicillin, streptomycin sulfate, norsulfazole, sulfadimezin, sunflower or liquid paraffin and emulsifier as an oil base in the following ratio of ingredients, UNITS and g / ml:
Penicillin potassium or sodium salt - 20,000 IU / ml
Streptomycin sulfate - 10,000 units / ml
Norsulfazole - 0.0035 g / ml
Sulfadimezin - 0.035 g / ml
Oil base - Up to 1 ml (8)
Mastaerosol, difurol-A, menersin A, mastivalin, lactopen, notil, aerodite and others are known for treating animals with mastitis, also containing antibiotics, sulfonamides and nitrofuran derivatives (9, 10, 11).

Known drug for the treatment and prevention of mastitis in cows, containing the antibiotic heliomycin, lanolin and paraffin oil in the following ratio of ingredients, wt.%:
Heliomycin - 2.0 - 4.0
Lanolin - 20.0 - 40.0
Vaseline oil - Up to 100 (12)
Known drug for the treatment and prevention of mastitis in cows, containing the antibiotic apramycin, lanolin and paraffin oil in the following ratio of ingredients, wt.%:
Apramycin - 2.0 - 5.0
Lanolin - 20.0 - 40.0
Vaseline oil - Up to 100 (13)
Known drug for the treatment and prevention of mastitis in cows, containing the antibiotic tylosintartrate, acetylsalicylic acid, ethyl alcohol, polypropylene glycol - 1200 and castor oil in the following ratio of ingredients, wt.%:
Tylosintartrate - 0.37 - 1.0
Acetylsalicylic acid - 0.6 - 1.6
Ethyl alcohol - 15.0 - 22.0
Polypropylene glycol - 1200 - 15.0 - 22.0
Castor oil - Up to 100 (14)
A common disadvantage of known drugs is low therapeutic efficacy.

 Firstly, chemotherapeutic agents already used by their nature have selective activity only in relation to certain microorganisms, and mastitis in cows is a polyetiological disease.

 Secondly, with repeated use of antibiotic-containing drugs, the development of resistance (resistance) to them was noted.

 Thirdly, antibiotics in the aqueous phase quickly lose their activity, and sulfonamides precipitate, which changes the concentration of the active substance at the injection site.

 Fourth, most preparations in the form of a suspension are stratified during storage, and vegetable oils are oxidized.

 In addition, for therapeutic and preventive measures for mastitis of cows, drugs based on antiseptic agents have been developed. In particular, drugs such as septogel, lasin, synthiod, and others were created on the basis of iodine, and a 10% solution of ichthyol is recommended for treatment with serous and catarrhal mastitis (15, 16). However, the active substances of these drugs belong to non-selective substances on microorganisms, in addition, they often irritate the epithelium of the milk ducts and alveoli, which can lead to hypogalactia and agalactia of the treated lobes.

 In a number of cases, drugs containing nitrofuran and quinoxaline derivatives, which inhibit the growth of microorganisms resistant to sulfanilamides and antibiotics, have begun to be used to treat mastitis in cows (17).

Known drugs for the treatment of mastitis in animals based on the indicated chemotherapeutic agents:
- dioxidine 1% solution containing 1,4-di-N-oxide 2, 3-bis (oxymethyl) quinoxaline, preservative and water for injection;
- Diofur - a complex preparation containing dioxidine, furatsilin and distilled water;
- difurol A, which contains furazolidone, furagin, dimethyl sulfoxide and polyethylene oxide in its composition (3).

 However, drugs in this group can cause various side reactions, such as allergies and hypersensitivity.

Also known drugs for the treatment of mastitis in animals produced by foreign companies:
- a mastic containing penicillin, streptomycin, superseptil in an oil suspension (Medimpex, Hungary);
- a multimast containing penicillin, neomycin, oxytetracycline hydrochloride, prednisolone and a base (Baimida, Ireland);
- Cloxavet M containing cloxacillite, penicillin, prednisone and a base (Pliva, Croatia);
- fort mastjet containing tetracycline, neomycin, bacitracin, prednisolone and base (Intervet, Holland);
- tototillin containing ampicillin, oxycycline, triglycerides (Bayer AG, Germany);
- synolox LC containing amoxicillin, clavulonic acid, prednisolone and a base (Pfizer, USA);
- Mastitis forte containing oxytetracycline 200 mg, neomycin 250 mg, bacitracin 2000 UE, prednisolone 10 mg (Intervet, Holland);
- lincocin-forte containing 100 mg of lincomycin and neomycin;
- methylprednisolone - 5 mg; polysorbate - 50 mg and distilled water to 10 ml (USA) and others (18, 19, 20, 21, 22).

 The disadvantages characteristic of domestic drugs are mainly inherent in foreign veterinary drugs.

The closest to the invention according to the set of essential features is widely used in practice, the drug Mastisan-A for the prevention and treatment of various forms of mastitis in animals, containing potassium or sodium salt of benzylpenicillin, streptomycin sulfate, sulfadimesin or norsulfazole, or norsulfazole sodium as a chemotherapeutic agent, herbal or liquid paraffin and emulsifiers as an oil base in the following ratio of ingredients, UNITS or g / ml administration dose:
Potassium or sodium salt of benzylpenicillin - 20,000 IU / ml
Streptomycin sulfate - 20,000 IU / ml
Sulfadimezin or norsulfazole or norsulfazole sodium - 0.07 g / ml
Oil base - up to 1.0 ml
The dose of administration is 5 ml (2, 5).

 The disadvantage of the prototype drug is its low therapeutic effectiveness, due to the fact that some microorganisms were resistant to the antibiotics included in the drug, or when they are reintroduced, resistance to them quickly increases, and during storage, the suspension is delaminated and the solid particles of sulfonamides precipitate in the dispersion medium. sediment.

 The objective of the present invention was to develop a combined preparation for the treatment of mastitis in animals with high prophylactic and therapeutic efficacy due to the introduction of an effective amount of an antibiotic and chemotherapeutic agent with a wide spectrum of antibacterial effect and dispersing the powder of the above ingredients in an oil base to form stable suspension, topical application of which would contribute to a better distribution of active substances in the affected lobes of the udder, a positive effect and a reduction in the treatment time for sick animals.

 The technical result from the use of the invention is to increase the therapeutic efficacy of the proposed drug.

The specified technical result was achieved by the creation of a drug for the treatment of mastitis in animals, characterized by the following set of features:
1) a drug for the treatment of mastitis in animals:
2) an antibiotic;
3) from antibiotics gentamicin sulfate in an effective amount;
4) gentamicin sulfate in an amount of 0.017 g / ml dose;
5) chemotherapeutic agent;
6) a quinoxaline derivative as a chemotherapeutic agent;
7) from quinoxaline derivatives, dioxidine in an effective amount;
8) dioxidine in an amount of 0.01 g / ml dose;
9) oil base;
10) oil;
11) emulsifiers;
12) mineral oil from oils;
13) brand M vaccine oil from mineral oils;
14) brand C vaccine oil from mineral oils;
15) brand B vaccine oil from mineral oils;
16) synthetic oil from oils;
17) PES-2 oil from synthetic oils;
18) PES-3 oil from synthetic oils;
19) MC oil from synthetic oils;
20) vegetable oil from oils;
21) oil in an amount up to 1.0 g / ml dose;
22) from emulsifiers, monoglyceride is soft in an effective amount;
23) from emulsifiers, solid monoglyceride in an effective amount;
24) mild monoglyceride in an amount of 0.03 g / ml administration dose;
25) solid monoglyceride in an amount of 0.03 g / ml administration dose.

The invention includes the following set of features that provide a technical result in all cases for which legal protection is sought:
1) a drug for the treatment of mastitis in animals:
2) an antibiotic gentamicin sulfate in an effective amount;
3) a quinoxaline derivative in an effective amount;
4) oil base;
5) oil;
6) emulsifiers;
7) of the emulsifiers, the monoglyceride is soft in an effective amount;
8) from emulsifiers, solid monoglyceride in an effective amount;
The proposed drug is also characterized by other signs expressing specific forms of execution or special conditions for its use:
1) the preparation contains gentamicin sulfate in an amount of 0.017 g / ml dose;
2) from quinoxaline derivatives, the preparation contains dioxidine in an effective amount;
3) the preparation contains dioxidine in an amount of 0.01 g / ml dose;
4) from oils, the preparation contains mineral oil or synthetic oil, or vegetable oil;
5) from mineral oils, the preparation contains brand M vaccine oil;
6) from mineral oils, the preparation contains brand C vaccine oil;
7) from mineral oils, the preparation contains brand B vaccine oil;
8) from synthetic oils, the preparation contains PES-2 oil;
9) from synthetic oils, the preparation contains PES-3 oil;
10) from synthetic oils, the preparation contains MC oil;
11) the preparation contains oil in an amount up to 1.0 g / ml of the dose of administration;
12) the preparation contains mild monoglyceride in an amount of 0.03 g / ml dose;
13) the preparation contains solid monoglyceride in an amount of 0.03 g / ml administration dose.

The signs of the invention, characterizing the proposed drug and coinciding with the signs of the prototype, including the generic concept, reflecting the purpose, are:
1) a drug for the treatment of mastitis in animals;
2) an antibiotic;
3) a chemotherapeutic agent;
4) oil base;
5) oil;
6) emulsifiers.

 Compared with the prototype drug, the essential distinguishing features of the present invention are the signs characterizing the introduction of gentamicin sulfate into the composition of the drug, effective in case of insufficient activity of other antibiotics, and a quinoxaline derivative bactericidal for microorganisms with low sensitivity and resistance to antibiotics and other chemotherapeutic agents, and from emulsifiers of soft monoglyceride and solid monoglyceride, taken in an effective amount.

The present invention is also characterized by other distinctive features that express specific forms of execution or special conditions for its use:
1) the preparation contains gentamicin sulfate in an amount of 0.017 g / ml dose;
2) from quinoxaline derivatives, the preparation contains dioxidine;
3) the preparation contains dioxidine in an amount of 0.01 g / ml dose;
4) from oils, the preparation contains mineral oil or synthetic oil, or vegetable oil;
5) from mineral oils, the preparation contains brand M vaccine oil;
6) from mineral oils, the preparation contains brand C vaccine oil;
7) from mineral oils, the preparation contains brand B vaccine oil;
8) from synthetic oils, the preparation contains PES-2 oil;
9) from synthetic oils, the preparation contains PES-3 oil;
10) from synthetic oils, the preparation contains MC oil;
11) the preparation contains oil in an amount up to 1.0 g / ml of the dose of administration;
12) the preparation contains mild monoglyceride in an amount of 0.03 g / ml dose;
13) the preparation contains solid monoglyceride in an amount of 0.03 g / ml administration dose.

 The proposed drug has a higher therapeutic efficacy compared with the prototype drug.

 As a result of the use of the proposed drug, the therapeutic effect increases with mixed infections, as well as in cases where the pathogen is not installed, as well as in the treatment of severe purulent-inflammatory processes in cows.

 At the same time, animals recover in 1-2 days after a single daily use (5 or 10 ml per affected udder) in acute mastitis and in 3-5 days with inflammation with severe purulent infection.

 The achievement of the technical result from the use of the proposed drug is explained, on the one hand, by the fact that gentamicin sulfate, as an antibiotic of a wide spectrum of antibacterial action, provides irreversible binding to specific receptors of bacterial ribosomes, disrupts the synthesis of cytoplasmic membranes, which leads to the death of bacterial cells; effective in case of insufficient activity of other antibiotics.

 On the other hand, dioxidine, which is part of the complex preparation, selectively inhibits DNA synthesis in a microbial cell, and is active against gram-negative, gram-positive pathogenic and conditionally pathogenic aerobic and anaerobic microorganisms of spore-forming and non-spore-forming species. It acts on bacterial strains resistant to other chemotherapeutic agents, including antibiotics. At the same time, the drug "sparingly" acts on lactic acid microflora.

 In addition, the dispersion of an antibiotic and dioxidine powder in an oil base with monoglycerides made it possible to obtain a kinetically stable suspension that provides a better distribution of the active substance in the affected udder lobes, and the oil base and monoglycerides used in the preparation have a softening and prolonging effect.

 The selected concentration of monoglycerides ensures the formation of a persistent non-stratifying emulsion, which ensures uniform distribution of the active principle and its prolonged absorption from the injection site. The use of only one type of monoglyceride or a change in their content leads to the separation of the emulsion and a decrease in the effectiveness of the drug.

 The analysis of the prior art by the applicant, including a search by patent and scientific and technical sources of information, and the identification of sources containing information about analogues of the proposed drug, made it possible to establish that the applicant did not find a source characterized by signs that were identical (identical) to all the essential features of the proposed drug. The definition from the list of identified analogues of the prototype, as the closest in the totality of the features of the analogue, made it possible to establish a set of significant distinguishing features in relation to the technical result perceived by the applicant in the proposed preparation set forth in the claims.

 Therefore, the proposed drug meets the condition of patentability "novelty."

 To check the conformity of the proposed drug to the patentability condition "inventive step", the applicant conducted an additional search for known solutions to identify features included in the distinctive part of the independent claim.

 Medicines for treating mastitis in animals containing antibiotics and oil-based chemotherapeutic agents are known. Information from them is given in the section "prior art" description of the invention. The salient features of the proposed drug are gentamicin sulfate introduced from its antibiotics, dioxidine from chemotherapeutic agents, and mild monoglyceride and solid monoglyceride from emulsifiers, taken in effective amounts.

 As an antibiotic gentamicin sulfate is known (3).

 The use of dioxidine as a chemotherapeutic agent is known (3, 17).

 It is also known to use monoglycerides as emulsifiers and stabilizers of edible fats, cosmetic creams, pharmaceutical ointments, plasticizers (23, 24, 25).

 The inventors proposed for the first time to introduce gentamicin sulfate, dioxidine, mild monoglyceride and solid monoglyceride into the composition of the proposed preparation, which made it possible to increase the therapeutic efficacy of the proposed preparation in comparison with the prototype preparation, i.e. the technical result is achieved only through the combined use of the above ingredients in the composition of the drug. The introduction of an effective amount of soft and hard monoglycerides as emulsifiers into the composition of the proposed preparation made it possible to obtain an aggregatively stable oil suspension of gentamicin sulfate and dioxidine powders, while the initial activity of the antibiotic is preserved (antibiotics quickly lose their activity in aqueous solutions). Adsorbed on solid particles of powders of active substances, monoglyceride molecules form solvate shells around them and turn the suspension into a kinematically stable form. The result is a drug in which the dispersion medium is an oil with monoglycerides, and the dispersed phase is solid particles of powders of active substances. This form of the proposed drug provides a better distribution of active substances in the affected lobes of the udder, prolonging their action, does not cause an adverse reaction of its tissues and reduces the treatment time for sick animals. Thus, only in the aggregate are the distinguishing features of the proposed drug ensure the achievement of a technical result, that is, an increase in the therapeutic effectiveness of the drug.

 The search results showed that the proposed solution does not follow explicitly for the specialist from the prior art set forth in the corresponding section of the description (no solutions having features matching the totality of distinctive features of the present invention have been identified), and the influence of the essential features of the proposed inventions of transformations to achieve a technical result.

 Therefore, the proposed drug meets the condition of patentability "inventive step". The essence of the invention is illustrated by examples of its use, which does not limit the scope of the invention.

Example 1
To prepare 100 ml of the drug, the active substances or the dispersed phase are used in the following composition and amount:
Gentamicin sulfate - 1.7 g
Dioxidine - 1.0 g
As a dispersed medium, oils are used:
mineral -
vaccine oil, grade M (26), or vaccine oil, grade C (27), or vaccine oil, grade B (28);
or synthetic -
PES-2 oil, or PES-3 oil (29), or MC oil (30),
or vegetable (31) in an amount up to 100 ml,
emulsifiers:
Soft monoglyceride - 3 g
Solid Monoglyceride - 3 g
To obtain a dispersed medium, 6 g of monoglycerides are dissolved at a temperature of 80 ^{° C.} in oil added to 100 ml, and the mixture is autoclaved at a temperature of 120 ^{° C.} for 1.5-2 hours.

A suspension of antibiotic and dioxidine powder is introduced into the dispersion medium cooled to 25-30 ^o C, passed through a colloid mill (JV brand, Germany) with a gap of OO knives for 10 minutes and immediately packed.

One dose (10 ml) of the drug should contain, g / dose of administration:
Gentamicin sulfate - 0.17
Dioxidine - 0.1
Soft monoglyceride - 0.3
Solid monoglyceride - 0.3
Oil - Up to 10.0
In appearance, the drug is a stable oily suspension of a viscous consistency with a specific smell, cream color. At temperatures above 35 ^o With the suspension has a liquid consistency. The drug, prepared on mineral, synthetic or vegetable oils, does not have significant differences in physico-chemical characteristics of the suspension and its therapeutic effectiveness.

The drug completely retains its original properties and does not delaminate within 24 months of storage at room temperature 20-25 ^o C.

 The drug is used to treat all forms of inflammation of the udder, and especially in severe suppurative inflammatory process.

Before the introduction of the drug, milk is discharged from the diseased quarter of the udder and disposed of, the nipple is disinfected. The contents of the syringe tube or vial are heated to 35 ^° C before use, shaken thoroughly until a uniform suspension is obtained, from the vial they are filled into a sterile syringe with a capacity of 10 ml. Then, tightly pressing the cannula of the syringe to the outer opening of the nipple canal, the drug is administered by carefully pressing the piston of the syringe into the nipple cistern of the udder. After the introduction, a light massage of the nipple of the affected quarter of the udder is carried out from the bottom up. Depending on the severity of the inflammatory process, the drug is administered after evening milking at a dose of 10 ml with an interval of 24 hours until the injured lobe of the udder is completely cured.

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

 The use of milk for people is allowed provided that the clinical signs of mastitis disappear completely and normal milk properties are acquired by reaction with 2% mastidine and a sedimentation test.

 Slaughter of animals for meat is allowed no earlier than 10 days after the last injection of the drug. The meat of animals forced to be killed earlier than the specified time, can be used for the production of meat and bone meal or for feed to fur animals.

Example 2
Tests of the proposed drug prepared in mineral, synthetic or vegetable oils, containing, g / ml dose of administration:
Gentamicin Sulfate - 0.017
Dioxidine - 0.01
Soft monoglyceride - 0.03
Solid monoglyceride - 0.03
Mineral or synthetic oil, or vegetable oil - Up to 1.0
This drug is prepared as described in example 1.

 Initially, we studied the effect of the drug on the body and mammary gland of lactating clinically healthy cows. At the same time, 3 samples of the preparation prepared with mineral, synthetic and vegetable oils were introduced intracisternally to 6 heads of clinically healthy cows (2 heads for each sample) of Simmental breed for 2-3 months of lactation. In this case, the drug was administered in 2 quarters of the udder, and the other two were left as controls.

 As a result, it was found that after intracisternal administration of the drug, no cases of changes in the general condition of the animal organism (temperature, pulse rate, number of respiratory movements, cardiac tremors, scar reduction) were observed.

 When studying the effect of the drug on the mammary gland of lactating cows, it was found that the reaction of milk from experimental quarters with a 2% solution of mastidine for 24-48 hours was doubtful. Calculation of somatic cells in the milk of experimental and control quarters showed that the number of somatic cells increased by 24 hours in the secret of experimental and less in the control quarters of the udder and decreased to the physiological norm after 72 hours in the experimental fractions and after 48 hours in the control. During the 3-day observation period, no changes were found in both the pH of milk and the daily milk yield. The research results are shown in table 1.

 As a result of experience in studying the irritating effect of the drug on the mammary gland of lactating cows, it was found that the drug causes only insignificant, fast-passing irritation of the tissues of the udder, belongs to the group of drugs carried by animals, and can be recommended for the treatment of mastitis.

 For a comparative assessment of the therapeutic effectiveness of the proposed drug, made on mineral, synthetic and vegetable oils, and the prototype drug in the acute course of mastitis, 8 groups of cows were formed (15-18 animals each), patients with latent and serous mastitis, respectively. Animals were selected for clinical signs and test milk donations. The therapeutic effectiveness of the proposed drug, prepared in various oils, did not have significant differences.

 The proposed drug in comparison with the prototype can reduce the average frequency of injections with latent mastitis by 59%, with serous - by 64.3%, the recovery period by an average of 1.6 days.

 As a rule, already on the second day, clinical improvement of sick cows was noted, and recovery occurred on the 2nd-3rd day. Side effects were not observed.

 The research results are presented in table 2.

 Example 3

Tests of the proposed drug, prepared in mineral oil and containing, g / ml dose of administration:
Gentamicin Sulfate - 0.017
Dioxidine - 0.01
Soft monoglyceride - 0.03
Solid monoglyceride - 0.03
Oil - Up to 1.0
This drug is prepared as described in example 1.

 A comparative assessment of the therapeutic effectiveness of this formulation of the proposed drug and the prototype drug was carried out in the treatment of catarrhal and purulent mastitis in cows. Moreover, the proposed drug was used immediately after manufacture and after 24 months of storage. In these experiments, cows often observed purulent-fibrinous inflammation of the udder, and mastitis was differentiated by detecting fibrin or a large number of purulent bodies in milk. In the presence of flakes and pus in secret, a soda-salt solution was preliminarily introduced into the udder, and after 20-30 minutes the injected solution was crushed and the corresponding medicinal product was administered. The therapeutic efficacy of the proposed drug was 95.0-100.0% and the prototype drug - 65.2-72.9%. At the same time, the therapeutic effectiveness of the drug did not have significant differences both in freshly prepared and after storage for 24 months.

 The test results are shown in table 3.

 Example 4

 A comparison of the therapeutic efficacy of the proposed drug and the prototype drug was carried out under the conditions of wide industrial experience in various farms of the Vladimir region. The test results are summarized in table 4.

For an objective assessment of the therapeutic effectiveness of the drugs, the results of the experiments were processed biometrically. Statistical evaluation was performed using the chi-square test. As a result, it was found that the value of the chi-square criterion when comparing the therapeutic efficacy of the proposed drug and the prototype drug was 29.37 (χ $\genfrac{}{}{0ex}{}{\text{2}}{\text{, 0.01}}$ = 6.63). Thus, at a significance level of 0.01, the drugs significantly differ (P> 0.99), which confirms the advantage of the proposed drug.

Thus, the above information indicates the fulfillment when using the invention of the following set of conditions:
- the proposed drug, embodying the invention, is intended for use in veterinary medicine;
- for the proposed invention in the form as described in the independent claim, the possibility of its implementation using the means and methods described in the application or known prior to the priority date is confirmed;
- when using the proposed drug, a technical result is achieved, provided by the objective of the invention: a preparation is obtained, characterized in that it has higher therapeutic efficacy compared to the prototype drug due to the use of gentamicin sulfate as an antibiotic of a wide spectrum of antibacterial action and dioxidine effective in infections, it is difficult treatable with other antimicrobial agents, in the form of a stable suspension in an oil base, does not irritate e on the udder tissue, and also accelerates the regeneration of damaged tissue.

Sources of information
1. Studentsov AP, Shipilov BC et al. Veterinary obstetrics, gynecology and biotechnology of reproduction. M .: Kolos, 1999, p. 357-369.

 2. Ivashura A.I. The system of measures to combat mastitis of cows. - M.: Rosagropromizdat, 1991, p. 168-201.

 3. Klenova I.F., Yaremenko N.A. Veterinary drugs in Russia. Directory. - M.: Selkhozizdat, 2000, 544 p.

 4. Klenova I.F., Ilyukhina I.N., Pisanova L.A. Foreign veterinary drugs in Russia. Directory. M .: "Evers Company", 1999, 314 p.

 5. Instruction for the use of Mastisan-A for the treatment of cows with mastitis. Approved GUV Ministry of Agriculture of the USSR 10.25.82 (prototype).

 6. Instruction for the use of Mastisan-B for the treatment of cows with mastitis. Approved GUV Ministry of Agriculture of the USSR, 10.22.82.

 7. Instruction for the use of Mastisan-E for the treatment of cows with mastitis. Approved Ministry of Agriculture of the USSR, 10.22.82.

 8. Instruction for the use of Masticide for the treatment of cows with mastitis. Approved GUV Ministry of Agriculture of the USSR 10/14/81.

 9. Veterinary drugs. Handbook / Ed. HELL. Tretyakova. - M.: Agropromizdat, 1988, 319 p.

 10. Goncharov V.P., Karpov V.A., Yakimchuk I.P. Prevention and treatment of animal mastitis - M .: Rosselkhozizdat, 1987, 174 p.

 11. Mirolyubov MG, Preobrazhensky O.N. Treatment and prevention for mastitis in cows // Veterinary medicine, 1999, 10, p. 33-36.

12. RF patent 2058781; IPC ⁶ A 61 K 35/74, 31/00; 04/27/96.

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14. RF patent 1684981; IPC ⁶ A 31 K 31/00; 02/27/95.

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Claims (15)

 1. A drug for the treatment of mastitis in animals, containing at least one antibiotic and one chemotherapeutic agent, oil and emulsifiers as an oil base, characterized in that the drug contains gentamicin sulfate from antibiotics, a derivative of quinoxaline from chemotherapeutic substances, and from emulsifiers - monoglyceride is soft and monoglyceride is solid, taken in an effective amount.  2. The drug according to p. 1, characterized in that it contains gentamicin sulfate in an amount of 0.017 g / ml dose of administration.  3. The drug according to claim 1, characterized in that the quinoxaline derivative contains dioxidine in an effective amount.  4. The drug according to p. 3, characterized in that it contains dioxidine in an amount of 0.01 g / ml dose of administration.  5. The drug according to claim 1, characterized in that the oil contains mineral oil, or synthetic oil, or vegetable oil.  6. The drug according to p. 5, characterized in that the mineral oil contains vaccine oil brand M.  7. The drug under item 5, characterized in that the mineral oil contains vaccine oil brand C.  8. The drug under item 5, characterized in that the mineral oil contains vaccine brand B.  9. The drug according to claim 5, characterized in that the synthetic oil contains PES-2 oil.  10. The drug according to p. 5, characterized in that the synthetic oil contains PES-3 oil.  11. The drug according to p. 5, characterized in that the synthetic oil contains MC oil.  12. The drug according to any one of paragraphs. 1, 6-11, characterized in that it contains oil in an amount up to 1.0 g / ml dose of administration.  13. The drug according to p. 1, characterized in that it contains soft monoglyceride in an amount of 0.03 g / ml dose of administration.  14. The drug according to p. 1, characterized in that it contains solid monoglyceride in an amount of 0.03 g / ml dose of administration. 15. The drug according to any one of paragraphs. 1-14, characterized in that it contains gentamicin sulfate, dioxidine, oil, soft monoglyceride and solid monoglyceride in the following ratio, g / ml dose:
Gentamicin Sulfate - 0.017
Dioxidine - 0.01
Soft monoglyceride - 0.03
Solid monoglyceride - 0.03
Oil - Up to 1.0

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