RU2180564C1 - Preparation to treat mastitis in animals - Google Patents

Abstract

FIELD: veterinary science. SUBSTANCE: in case of mastitis, the therapy is conducted by using a preparation which contains, g/ml injection dose: neomycin sulfate 0.02, lincomycin hydrochloride 0.02, soft monoglyceride 0.03, distilled monoglyceride 0.03, oil - up to 1.0. Curative dose for intracisternal injection is 5 and 10 ml. EFFECT: increased therapeutic efficiency. 1 cl, 5 tbl, 5 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 enzotic 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 early diagnosis of inflammation and the treatment of latent and serous mastitis. 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, 5).

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 (6).

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 (7)
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 (8).

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 (9)
Mastaerosol, difurol-A, menersin A, mastivalin, lactopen, notil, aerodite and others are known for treating animals with mastitis, which also contain antibiotics, sulfonamides and nitrofuran derivatives (10, 11, 12).

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 (13)
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 (14)
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 (15)
A common disadvantage of known drugs is low therapeutic efficacy.

 First, the chemotherapeutic agents 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, such drugs 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 (16, 17). 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, oxycyllin, triglycerides (Waueg 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 (19, 20, 21, 22, 23).

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

The closest to the present invention in terms of essential features is the widely used Mastisan-A preparation 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, vegetable or liquid paraffin and emulsifiers as an oil base in the following ratio of ingredients, UNITS or g / ml dose of administration:
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, 6).

 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 re-introduced, resistance to them quickly increases, and when stored, the suspension delaminates 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 treating mastitis in animals by introducing an effective amount of antibiotics having a wide spectrum of antibacterial action into the preparation and dispersing the antibiotic powder in an oil base to form a stable suspension, topical application of which promotes better distribution and absorption active substance in the affected lobes of the udder, a positive effect and a reduction in the treatment time of patients is alive from

 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) antibiotics;
3) from antibiotic neomycin sulfate;
4) neomycin sulfate in an effective amount;
5) neomycin sulfate in an amount of 0.02 g / ml dose;
6) from antibiotic lincomycin hydrochloride;
7) lincomycin hydrochloride in an effective amount;
8) lincomycin hydrochloride in an amount of 0.02 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) from mineral oils, liquid paraffin;
17) oil in an amount up to 1.0 g / ml dose;
18) of the emulsifiers, the monoglyceride is soft in an effective amount;
19) from emulsifiers, monoglyceride distilled in an effective amount;
20) soft monoglyceride in an amount of 0.03 g / ml dose;
21) distilled 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) antibiotics;
3) from antibiotics neomycin sulfate in an effective amount;
4) from lincomycin antibiotic hydrochloride in an effective amount;
5) oil base;
6) oil;
7) emulsifiers;
8) of emulsifiers, the monoglyceride is soft in an effective amount;
9) from emulsifiers, monoglyceride distilled 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 neomycin sulfate in an amount of 0.02 g / ml dose;
2) the drug contains lincomycin hydrochloride in an amount of 0.02 g / ml dose;
3) from oils, the preparation contains mineral oil;
4) from mineral oils, the preparation contains vaccine oil of brand M;
5) from mineral oils, the preparation contains vaccine oil of grade C;
6) from mineral oils, the preparation contains brand B vaccine oil;
7) from mineral oils, the preparation contains liquid paraffin;
8) the preparation contains oil in an amount up to 1.0 g / ml of a dose of administration;
9) the preparation contains mild monoglyceride in an amount of 0.03 g / ml of the dose of administration;
10) the preparation contains distilled monoglyceride in the amount of 0.03 g / ml of the dose of administration.

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) antibiotics;
3) oil base;
4) oil;
5) emulsifiers.

 Compared with the prototype drug, the essential distinguishing features of the present invention are the signs characterizing the introduction of neomycin sulfate and lincomycin hydrochloride into antibiotics, acting on a wide range of microorganisms and effective with insufficient activity of other antibiotics, and from soft and distilled monoglyceride emulsifiers 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 neomycin sulfate in an amount of 0.02 g / ml dose;
2) the drug contains lincomycin hydrochloride in an amount of 0.02 g / ml dose;
3) from oils, the preparation contains mineral oil;
4) from mineral oils, the preparation contains vaccine oil of brand M;
5) from mineral oils, the preparation contains vaccine oil of grade C;
6) from mineral oils, the preparation contains brand B vaccine oil;
7) from mineral oils, the preparation contains liquid paraffin;
8) the preparation contains oil in an amount up to 1.0 g / ml of a dose of administration;
9) the preparation contains mild monoglyceride in an amount of 0.03 g / ml of the dose of administration;
10) the preparation contains distilled monoglyceride in the amount of 0.03 g / ml of the dose of administration.

 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 neomycin sulfate has a wide spectrum of antibacterial activity, is active against many gram-positive and gram-negative microorganisms, including those resistant to other antibiotics (penicillin, streptomycin, levomycin, tetracycline). The mechanism of its action is due to irreversible binding to specific receptors of bacterial ribosomes and impaired synthesis of cytoplasmic membranes, which leads to the death of bacterial cells. On the other hand, the hydrochloride included in the complex drug lincomycin is effective against gram-positive microorganisms (staphylococci, streptococci), anaerobes, mycoplasmas and microorganisms resistant to other antibiotics. The mechanism of action is associated with the suppression of protein synthesis of microorganisms (24, 25, 26). Thus, the different spectrum and mechanism of action of antibiotics significantly increases the therapeutic efficacy of the combined drug.

 In addition, the dispersion of oil-based antibiotic powders with monoglycerides made it possible to obtain a kinetically stable suspension that provides better distribution and preservation of the active substance in the affected parts of the udder, 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. In the case of using only one type of monoglyceride or a change in their content, the emulsion becomes stratified and the effectiveness of the drug decreases.

 An analysis of the state of the art by the applicant, including a search by patent and scientific and technical sources of information, and 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 essential distinguishing features in relation to the applicant’s perceived technical result 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.

 Medications for the treatment of mastitis containing oil-based antibiotics are known. Information from them is given in the section "prior art" description of the invention to this application.

 Significant distinguishing features of the proposed drug are neomycin sulfate and lincomycin hydrochloride introduced into its composition from antibiotics, and mild monoglyceride and distilled monoglyceride from emulsifiers taken in an effective amount.

 The antibiotic neomycin sulfate is known (24, 25, 26).

 Lincomycin hydrochloride is also known as antibiotic (27, 28).

 The use of monoglycerides as emulsifiers and stabilizers of edible fats, cosmetic creams, pharmaceutical ointments, plasticizers is known (29, 30).

 The inventors proposed for the first time to introduce neomycin sulfate, lincomycin hydrochloride, mild monoglyceride and distilled monoglyceride into the composition of the proposed drug, which allowed to increase the therapeutic efficacy of the proposed drug in comparison with the prototype drug, i.e. the technical result is achieved only due to the combination of the use of the above ingredients in the composition of the drug. The introduction of an effective amount of soft and distilled monoglycerides as emulsifiers into the composition of the proposed preparation made it possible to obtain an aggregatively stable oil suspension of neomycin sulfate and lincomycin hydrochloride powders, while the initial activity of antibiotics is preserved (in aqueous solutions, antibiotics quickly lose their activity). 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 oil with monoglycerides, and the dispersed phase is solid particles of antibiotic powders. 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, i.e. increasing 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 the distinguishing features of the present invention have been identified), and the effect 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 execution, 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 composition and quantity:
Neomycin sulfate - 2.0 g
Lincomycin hydrochloride - 2.0 g
As a dispersion medium, oils are used:
Mineral - vaccine oil grade M (31), or vaccine oil grade C (32), or vaccine oil grade B (33), or liquid paraffin oil (34) in an amount of - Up to 100 ml
and emulsifiers:
Soft monoglyceride - 3 g
Distilled monoglyceride - 3 g
To obtain a dispersion medium, 6 g of monoglycerides are dissolved at a temperature of 80 ^{° C.} in oil added up to 100 ml, and the mixture is autoclaved at a temperature of 120 ^{° C.} for 1.5-2 hours.

A suspension of antibiotic powder is introduced into the dispersion medium cooled to 25-30 ^° C and passed through a colloid mill (brand JV, Germany) with a knife clearance of 00 for 10 minutes and immediately packed.

One dose (10 ml) of the drug should contain, g / dose of administration:
Neomycin sulfate - 0.2
Lincomycin hydrochloride - 0.2
Soft monoglyceride - 0.3
Distilled monoglyceride - 0.3
Oil - Up to 10.0
In appearance, the drug is a stable, oily suspension of viscous consistency with a specific odor, white. At temperatures above 35 ^o With the suspension has a liquid consistency. The drug, prepared on different mineral oils, has no significant differences in physicochemical parameters 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 from 0 to 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 an evening milking in a dose of 5 or 10 ml with an interval of 24 hours until the injured lobe of the udder is completely cured.

 During treatment and within 7 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 from the remaining quarters the udder is 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 properties of milk are acquired.

 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 on mineral, vaccine and paraffin oils, containing, g / ml dose of administration:
Neomycin Sulfate - 0.02
Lincomycin hydrochloride - 0.02
Soft monoglyceride - 0.03
Distilled monoglyceride - 0.03
Mineral oil, vaccine or liquid paraffin - 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, 2 samples of the preparation prepared with mineral, vaccine and petrolatum oils were administered intracisternally to 6 heads of clinically healthy cows (3 heads per sample) of a black-and-white breed at 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, vaccine and petrolatum oils, and the prototype drug in the acute course of mastitis, 6 groups of cows were formed (12-18 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 in acute mastitis by 39%, with serous by 61.4%, the recovery time on average by 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:
Neomycin Sulfate - 0.02
Lincomycin hydrochloride - 0.02
Soft monoglyceride - 0.03
Distilled 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. its 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 86.3-92.3% and the prototype drug - 65.2-77.7%. 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
Tests of the proposed drug, prepared in mineral oil and containing, g / ml dose of administration:
Neomycin Sulfate - 0.02
Lincomycin hydrochloride - 0.02
Soft monoglyceride - 0.03
Distilled monoglyceride - 0.03
Oil - Up to 1.0
The drug was prepared as described in example 1, only with intracisternal administration, its dose was 5 ml and 10 ml.

 A comparative assessment of the therapeutic efficacy of various doses (5 and 10 ml) of the proposed drug found that with latent and serous mastitis, the therapeutic effectiveness was not dose-dependent and amounted to 92.8-94.1%, but with catarrhal and purulent mastitis with an increase in the dose of the drug upon first administration, therapeutic efficacy is enhanced.

 The test results are shown in table 4.

Example 5
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 5. 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 (X ² _1.0.01 = 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 neomycin sulfate and lincomycin hydrochloride as antibiotics with a wide spectrum of antibacterial action and effective in case of insufficient activity other antibiotics, in the form of a stable suspension in an oil base, does not irritate tissue veni, 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.

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

 5. Subbotin V. M., Subbotin S. G., Alexandrov I. D. Modern medicines in veterinary medicine / Rostov-on-Don. "Phoenix". - 2000, 592 p.

 6. 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 g. (Prototype).

 7. 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 g.

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

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

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

 11. Goncharov V.P., Karpov V.A., Yakimchuk I.P. Prevention and treatment of mastitis in animals. -M .: Rosselkhozizdat, 1987, 174s.

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

13. RF patent 2058781; IPC ⁶ A61K35 / 74, 31/00; 04/27/96

14. RF patent 2058782; IPC ⁶ A61K35 / 74, 31/00; 04/27/96

15. RF patent 1684981; IPC ⁶ A61 K 31/00; 02/27/95

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Claims (12)

 1. A drug for the treatment of mastitis in animals, containing antibiotics, oil and emulsifiers as an oil base, characterized in that the drug contains neomycin sulfate and lincomycin hydrochloride from antibiotics, and mild monoglyceride and distilled monoglyceride from emulsifiers, taken in an effective amount.  2. The drug according to p. 1, characterized in that it contains neomycin sulfate in an amount of 0.02 g / ml dose of administration.  3. The drug according to p. 1, characterized in that it contains lincomycin hydrochloride in an amount of 0.02 g / ml dose of administration.  4. The drug under item 1, characterized in that the oil contains mineral oil.  5. The drug according to p. 4, characterized in that the mineral oil contains vaccine oil brand "M".  6. The drug according to p. 4, characterized in that the mineral oil contains vaccine oil brand "C".  7. The drug under item 4, characterized in that the mineral oil contains vaccine oil brand "B".  8. The drug according to claim 4, characterized in that the mineral oil contains liquid paraffin.  9. The drug according to any one of paragraphs. 4-8, characterized in that it contains oil in an amount of 0.9-0.91 g / ml dose of administration.  10. The drug according to p. 1, characterized in that it contains soft monoglyceride in an amount of 0.03 g / ml dose of administration.  11. The drug according to p. 1, characterized in that it contains distilled monoglyceride in an amount of 0.03 g / ml dose of administration. 12. The drug according to any one of paragraphs. 1-11, characterized in that it contains neomycin sulfate, lincomycin hydrochloride, oil, soft monoglyceride and distilled monoglyceride in the following ratio, g / ml dose:
Neomycin Sulfate - 0.02
Lincomycin hydrochloride - 0.02
Soft monoglyceride - 0.03
Distilled monoglyceride - 0.03
Oil - Up to 1.0

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