RU2350332C1 - Preparation for treatment and prevention of mastitis at cows in dry period - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns veterinary science area. The preparation for treatment and prevention of mastitis at cows in a dry period contains following components, wt %: Doxycycline 2.5-4.5; emulsion wax 5; aluminium stearate 3; liquid paraffin - to 100. The preparation in warmed up to 38°C a kind is administered intracisternally into all shares of an udder by means of a syringe or an unit-dose syringe in a dose by of 10 ml unitary after last milking.

EFFECT: preparation use allows raising efficiency of treatment and preventive maintenance of mastitis at cows in a dry period.

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Description

The invention relates to the field of veterinary medicine.

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

Breast diseases in 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 the needs of the country's population. Therefore, it is necessary to develop new highly effective means and methods of combating mastitis. In the complex against mastitis, the leading importance is given to early diagnosis and timely treatment of mastitis in cows.

For the treatment and prevention of mastitis in cows during dead wood, antimicrobial drugs are used, including antibiotics, sulfonamide, nitrofuran and other agents. But not all of them give the expected effect. This is primarily due to a decrease in the sensitivity of microflora, which causes mastitis, to drugs. In this regard, there is a need to create new drugs of prolonged action.

A septogel containing iodpovidone and a gel base was taken as an analogue to the proposed preparation [Veterinary preparations in Russia. Directory. M., 2004. Part 1. - S. 473].

The disadvantage of septogel is a decrease in the therapeutic effectiveness of the drug due to the rapid removal of its components from the mammary gland, since the drug is recommended for the treatment of mastitis in lactating cows and its prevention in dry animals. And the main condition for the development of funds for the treatment of mastitis in lactating cows is their rapid removal from the mammary gland in order to reduce the time for milk rejection.

The closest analogue of the drug we developed is masticide-2, which is recommended for the treatment and prevention of mastitis in cows during dead wood [Antibiotics, sulfonamides and nitrofurans in veterinary medicine: Reference book / V.F. Kovalev, I.V. Volkov, B.V. Violin and others. - M .: Agropromizdat, 1988. - P.124].

Masticide-2 is a complex preparation containing benzathine penicillin (bicillin-1), streptomycin sulfate, sulfadimezin, norsulfazole, vegetable oil and an emulsifier.

The disadvantage of the prototype drug is its low therapeutic efficacy, due to the fact that certain microorganisms (penicillin-resistant staphylococci) are resistant to antibiotics included in the drug or it is quickly developed to them. In addition, during storage, the drug exfoliates and the sulfonamides contained in the suspension precipitate, which reduces the effectiveness of the drug and can cause irritation of the mammary gland [S.M. Navashin, I.P. Fomina. Rational antibiotic therapy. Directory. M., "Medicine", 1982, pp. 23-25].

The technical result of the invention is to increase the effectiveness of the treatment and prevention of mastitis in cows during the dry period.

This goal is achieved by the use of a complex preparation consisting of doxycycline, emulsion wax, aluminum stearate and liquid paraffin, by introducing into the mammary gland of a cow through the nipple canal after the last milking for therapeutic and preventive purposes.

The preventive effectiveness of the drug is increased by increasing the shelf life of the active substance in the mammary gland.

The drug for the treatment and prevention of mastitis in cows during the dry period consists of the following components, wt.%:

Doxycycline 2.5-4.5%,

Emulsion Wax 5%,

Aluminum stearate 3%,

Vaseline oil - up to 100%.

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

Doxycycline 3.5%,

Emulsion Wax 5%,

Aluminum stearate 3%,

Vaseline oil - up to 100%.

According to the spectrum of antibacterial action, doxycycline corresponds to other tetracyclines, and in some cases it surpasses them in terms of in vitro activity against staphylococci, streptococci and enterococci. Doxycycline has a wide antimicrobial spectrum and prolonged action, aluminum stearate enhances the prolonged action, and emulsion wax creates a stable suspension (emulsion) of the complex preparation [S.M. Navashin, I.P. Fomina. Rational antibiotic therapy. Directory. M., "Medicine", 1982, pp. 205-208].

The advantage of doxycycline over other tetracyclines is that it is 5-10 times better soluble in fats, therefore it is absorbed faster and more evenly, has a pronounced tropism in relation to the reproductive organs, has some anti-inflammatory properties, and is also the only antibiotic from this group that has a postantibiotic effect [A.N. Grechukhin. A new remedy for the bacterial symptom complex. Veterinary medicine No. 8, 2006, p.6-8].

It is known to use wax emulsifier as an emulsifier and stabilizer of cosmetic creams, pharmaceutical ointments, plasticizers [Chemical Encyclopedia. M .: Publishing. “Owls. Encyclopedia ”, 1989, vol. 1, p. 584-585].

The drug for the treatment of subclinical mastitis in cows and the prevention of mastitis during the dry period is administered intracisternally in all lobes of the udder with a syringe or syringe tube in a dose of 10 ml once, after the last milking. Before the introduction of the drug, milk is discharged from all lobes of the udder, the nipple is disinfected. The contents of the syringe tube or vial are heated to 38 ° C before use, shaken thoroughly until a uniform suspension is obtained, 10 ml are taken from the vial into a sterile syringe. Then tightly pressing the cannula of the syringe to the outer opening of the nipple canal, the drug is administered by pressing the syringe plunger into the teat cistern of the udder. After the introduction of the drug, massage the nipples of the udder from the bottom up.

The drug is made as follows. To obtain a dispersion medium, 5 g of emulsion wax and 3 g of aluminum stearate are dissolved at a temperature of 80 ° C in vaseline oil added to 100 ml, and the mixture is autoclaved at a temperature of 120 ° C for 1.5-2 hours. 2.5-4.5 g of doxycycline are added to the mixture cooled to 25-30 ° C, the stirrer is turned on for 15 minutes and the preparation is immediately packed.

The quality indicators of the drug of three experimental batches were studied during storage for one year. It was established that the appearance, color, authenticity, mass fraction of doxycycline, microbial purity and mechanical inclusion of the drug meet the requirements of technical conditions.

The drug’s effectiveness was tested on cows of Dolzhanskoye CJSC in the Veidelevsky District of the Belgorod Region, Manino Kalacheevsky CJSC in the Voronezh Region, Uspenskoye Non-Profit Organization of Livensky District, Oryol Region.

The essence of the technical solution is illustrated by examples.

Example 1

To identify the optimal ratio of components and the effectiveness of the drug, 3 formulations were compiled.

Recipe No. 1: doxycycline - 4.5%, emulsion wax 5%, aluminum stearate 3% and liquid paraffin up to 100%.

Recipe No. 2: doxycycline - 3.5%, emulsion wax 5%, aluminum stearate 3% and liquid paraffin up to 100%.

Recipe number 3: doxycycline - 2.5%, emulsion wax 5%, aluminum stearate 3% and liquid paraffin up to 100%.

The effectiveness of prevention of mastitis in cows in the dry period was determined on cows of Holstein-Friesian breed 2-4 lactation (table 2). For this, 196 cows were selected that had mastitis during lactation, and when they were studied during the start-up period, the reaction of the secretion of the udder with a 2% solution of mastidine was negative.

The animals of the first, second and third groups were injected with a drug (of different formulations) for the treatment and prevention of mastitis in cows during dead wood, the fourth group - masticide-2 once intracisternally at a dose of 10 ml in a form heated to 38 ° C, in accordance with the instructions for the drug [Manual on the use of masticide-2. Approved by the GUV of the Ministry of Agriculture of the USSR on April 18, 1984], and the intact cows of the fifth group served as control.

Examination of animals and mammary gland (without secretion) was carried out on 10-15 days from the onset of dead wood and 10-15 days before the expected calving (when transferring them to the maternity ward). The effectiveness of the drug was determined by the incidence of mastitis on the first day after calving.

Table 1 The effectiveness of the prevention of mastitis in cows in the dry period A drug Total Experience Do not get mastitis Mastitis cows share cows % share % cows % share % Recipe 1 38 152 34 89.5 135 88.8 four 10.5 17 11,2 Recipe 2 40 149 39 97.5 143 96.0 one 2.5 6 4.0 Recipe 3 40 157 39 97.5 152 96.8 one 2.5 5 3.2 Masticide-2 thirty 118 24 80.0 101 85.6 6 20,0 17 14,4 The control 48 189 33 68.7 132 69.8 fifteen 31.3 57 30,2

From table 1 it follows that a high prophylactic effect was achieved when using the following composition of the drug for the treatment and prevention of mastitis in cows during the dry period: doxycycline; aluminum stearate; emulsion wax with a ratio of components of 3.5: 3.0: 5.0 (formulation 2). An increase in the concentration of doxycycline to 4.5% did not lead to a significant increase in efficiency.

The effectiveness of the drug for the treatment of mastitis in cows during dead wood was determined on cows of Holstein-Friesian breed 2-4 lactation (table 2).

For this, 117 patients with subclinical mastitis of cows at the start were selected. Animals were divided according to the principle of analogues into 4 groups. The cows of the first, second and third groups were injected with the drug for the treatment and prevention of mastitis in cows during dry periods, of various formulations, once intracisternally at a dose of 10 ml, warmed up to 38 ° C, the fourth group - masticide-2 in accordance with the instructions for the drug [ Manual for the use of masticide-2. Approved by the GUV Ministry of Agriculture of the USSR on April 18, 1984]. The animals were monitored, the effectiveness of the drug was determined by the incidence rate of cows with mastitis on the first day after calving.

table 2 The effectiveness of the treatment of subclinical mastitis and the prevention of mastitis in cows in the dry period A drug Total Experience Recovered Left sick cows share cows % share% cows % share % Recipe 1 32 72 27 84.3 59 81.9 5 15.7 13 18.5 Recipe 2 thirty 43 28 93.3 40 93.0 2 6.7 3 7.0 Recipe 3 29th 41 28 96.5 39 95.1 one 3,5 2 4.9 Masticide-2 26 39 19 73.1 31 79.5 7 19.2 8 20.5

As can be seen from the data presented (table 2), a single intracisternal administration of the drug for the treatment and prevention of mastitis in cows during the dry period at the end of the run for cows with subclinical mastitis leads to a recovery of 84.3-96.5% of animals, 81.9- 95.1% of the breast. At the same time, after the use of masticide-2, recovery occurs only in 73.1% of cows and 79.5% of the shares of the mammary gland. An increase in the concentration of doxycycline from 3.5% to 4.5% did not lead to a significant (93.3 and 96.3%) increase in the effectiveness of the drug.

Thus, a high prophylactic effect was achieved by using the following composition of the drug for the treatment and prevention of mastitis in cows during the dry period: doxycycline; aluminum stearate; emulsion wax at a ratio of 3.5: 3.0: 5.0 (formulation 2).

Example 2

The irritating effect of the drug on the mammary gland of cows (table 3). 3 clinically healthy lactating cows were selected. The drug, heated to a temperature of 38 ° C, in an amount of 10 ml was injected intracisternally into the left front lobe of the udder after preliminary secretion and treatment of the nipple with 70 ° ethanol. The drug was not injected into the right anterior lobe; it served as a control. Before administration of the drug and 3, 6, 12, 24, 48, and 72 hours after its administration, a general clinical examination of animals, mammary gland, and a reaction with a 2% mastidine solution was performed. The number of somatic cells was counted in the laboratory and the assay sample was taken into account.

Table 3 The change in the content of SC in the secret of the udder of healthy cows after intracisternal administration of the drug for the treatment and prevention of mastitis in cows during the dry period Udder shares Study Dates before introduction 3 hours 6 o'clock 12 hours 24 hours 48 hours 72 hours the number of SC thousand / ml Left front (experience) 206.3 ± 19.4 399.7 ± 33.9 742.3 ± 53.6 1639.3 ± 256.2 1879.6 ± 185.3 704.6 ± 98.5 228.7 ± 23.8 Right front (control) 238.3 ± 27.4 312.0 ± 36.8 519.0 ± 26.2 612.7 ± 74.3 680.0 ± 29.3 538.7 ± 20.7 311.0 ± 14.3

Table 4 The effect of the drug for the treatment and prevention of mastitis in cows during the dry period on indicators of the general condition of the body Study time, h Indicators Temperature ° C Pulse once per minute Breath once per min Rumination every 5 minutes Before introduction 37.9 ± 0.06 76.0 ± 0.78 15.7 ± 0.20 4.7 ± 0.20 After administration, in: 3 hours 37.9 ± 0.08 74.3 ± 0.98 17.0 ± 0.40 4.7 ± 0.20 6 o'clock 37.9 ± 0.08 74.7 ± 1.37 16.0 ± 0.78 4.3 ± 0.20 12 hours 38.0 ± 0.04 75.0 ± 1.37 16.7 ± 0.20 4.0 ± 0.00 24 hours 38.0 ± 0.19 75.0 ± 0.98 15.7 ± 0.78 4.3 ± 0.20 48 hours 37.9 ± 0.06 75.6 ± 1.17 16.3 ± 0.40 4.7 ± 0.20 72 hours 37.8 ± 0.04 71.3 ± 0.40 18.0 ± 0.40 4.3 ± 0.20

The research results (table 3) on the effect of the drug for the treatment and prevention of mastitis in cows during the dry period on the mammary gland of clinically healthy lactating cows indicate that intracisternal administration of the drug leads to an increase in the number of somatic cells (irritating effect), which disappears after 72 hours.

It was found that after intracisternal administration of the drug for the treatment and prevention of mastitis in cows during dry period at a dose of 10 ml, an increase in the number of somatic cells occurs in 3 hours 1.93 times (from 206.3 ± thousand / ml to 399.7 ± 33 , 9), after 6 hours - at 3.59; after 12 hours - at 7.9; after 24 hours - at 9.11; after 48 hours - by 3.41 times and by 72 hours - it approaches the initial level (228.7 ± 23.8 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.

Thus, the drug for the treatment and prevention of mastitis in cows during dead wood has a moderate irritating effect on the mammary gland of cows, the signs of which disappear after 72 hours after administration. The drug does not adversely affect the clinical condition of animals. Indicators of temperature, respiratory rate, scar reduction after 3, 6, 12, 24, 48, and 72 hours after drug administration did not have significant differences from those before its administration (table 4).

Example 3. To test the antimicrobial activity of the drug for the treatment and prophylaxis of mastitis in cows during dry periods, an experiment was conducted in comparison with the prototype. The antimicrobial activity (BS - bacteriostatic activity, BC-bactericidal activity) of the claimed drug was determined by the method of serial dilutions. The results are presented in table 5.

Table 5 Indicators of antimicrobial activity of the drug for the treatment and prevention of mastitis in cows during the dry period to various microorganisms No. p / p Microbe culture Bacteriostatic concentration μg / ml Bactericidal concentration μg / ml one. Staphylococcus aureus-209 P 7.8 7.8 2. Staphylococcus aureus-589 7.8 7.8 3. Streptococcus agalactic-586 3.9 7.8 four. Streptococcus agalactic-587 3.9 3.9 5. Streptococcus gr. D-588 7.8 250,0 6. Streptococcus gr. D-640 31.25 31.25 7. Escherichia coli-643 7.8 250,0

Thus, the drug for the treatment and prevention of mastitis in cows during dead wood has a higher, compared with the prototype, prophylactic and therapeutic efficacy due to the use of doxycycline as an effective antibiotic with a wide spectrum of activity and with insufficient activity of other antibiotics, in the form of a stable suspension in oil a basis that has a prolonged effect and does not irritate breast tissue.

Claims (1)

A drug for the treatment and prevention of mastitis in cows during dead wood, containing an antibiotic, emulsifier and an oil base, characterized in that it contains doxycycline as an antibiotic, emulsion wax as an emulsifier, liquid paraffin as an oil base and additionally contains aluminum prolongator stearate in the following ratio of components, wt.%:
Doxycycline 2.5-4.5% Emulsion Wax 5% Aluminum stearate 3% Vaseline oil up to 100%