RU2333759C1 - Medication for treatment and prevention of postnatal cow endometritis and sow metritis-mastitis-agalactia - Google Patents

Abstract

FIELD: medicine, veterinary.

SUBSTANCE: invention concerns veterinary. The medication for treatment and prevention of postnatal endometritis in cows and metritis-mastitis-agalactia in sows contains, mass %: norfloxacin - 0.4-1.0; dioxidine - 0.5-0.9; dimethylsulfoxide - 30-40, the rest being distilled water. The medicine is administered to cows in endometrial form with Janet's syringe, 3-4 times for treatment purposes in dose of 200 ml for the first two times and 150 ml later over 48 hour interval till recovery, and one time for prevention purposes, in dose of 200 ml immediately after operative placenta separation or in 6-12 hours in cases of the pathology prevalence at the farm. Medication is administered to sows in endometrial form by means of artificial insemination device for swines POS-5, one time for treatment purposes in dose of 0.7 ml per kg of body weight, repeated over 24 hours if necessary, the prevention dosage comprising 0.5 ml per kg of body weight one time in 6-12 hours after farrow.

EFFECT: obtaining medication for prevention and treatment of postnatal endometritis, with wider range of antimicrobial effect and higher antimicrobial activity compared to its analogues.

6 tbl, 6 ex

Description

The invention relates to the field of veterinary medicine, in particular to preparations for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows.

Acute postpartum endometritis is an inflammation of the predominantly uterine mucosa. Depending on the nature of the inflammation, postpartum endometritis is divided into catarrhal, purulent-catarrhal and fibrinous. Purulent-catarrhal endometritis is believed to be the main form of postpartum endometritis in cows. Acute postpartum endometritis is clinically manifested on the 8-10th day after childbirth, less often on the 6-7th day and is characterized by abundant secretion of exudate (mucous, purulent-mucous, fibrinous) of a liquid consistency of gray-brown or yellow-brown color. Postpartum endometritis is recorded in 20-57% of calving cows.

Metritis-mastitis-agalactia is an acute disease of sows that occurs as a general syndrome in the first two days after farrowing and manifests itself as inflammation of the uterus, mammary gland, as well as a decrease (hypogalactia) or cessation (agalactia) of milk secretion. The disease is manifested by an increase in body temperature to 39.8-40.8 ° C, increased heart rate and respiration, inhibition of the general condition, decreased or terminated intake of food and water. Sows are lying, not allowing piglets to the nipples. From the genital tract, mucopurulent exudate of a liquid or semi-liquid consistency is secreted, in an amount of 10-20 to 200-300 ml. The external genitalia, the mucous membrane of the vagina are hyperemic. The main form of breast inflammation is subclinical mastitis, which affects up to 40-60% of the functioning lobes of sows. Clinically expressed mastitis is recorded in 12-20% of sick sows.

For the treatment and prevention of postpartum diseases in cows and sows, antimicrobial agents 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 the uterine microflora to drugs. In this connection, there is a need to create new complex preparations that do not contain antibiotics.

As analogues, we took 2 drugs used to treat cows, patients with postpartum endometritis, and sows, patients with metritis-mastitis-agalactia.

Neofur is a complex preparation containing neomycin, furazolidone and a gelatin-glycerin base. Used for the treatment and prevention of inflammatory process in the uterus of animals. The main disadvantage of neofur is the rapid decrease in its therapeutic and prophylactic effectiveness due to a decrease in the sensitivity of microflora and the need for its multiple administration due to the absence of penetrating substances at the base of the drug / Chervyakov D.K. et al. Medicines in veterinary medicine. - M .: Kolos, 1977, p.342 /.

Ichthyofur is a complex antiseptic, anti-inflammatory drug containing 2 g of ichthyol and 0.3 g of furazolidone on a gelatin-glycerin base in one intrauterine device. Used for the prevention and treatment of inflammatory processes of various etiologies in the uterus, in the cervix and in the vagina in animals. The main disadvantage of ichthyofur is that the sticks of the drug slowly dissolve when they are introduced into the uterine cavity, creating an insufficient area of contact of the active components with the uterine mucosa, which reduces its effectiveness / Chervyakov D.K. et al. Medicines in veterinary medicine. - M .: Kolos, 1977, p. 381 /.

The closest analogue of the drug developed by us is the preparation diometer.

Diometer is a complex preparation containing kanamycin monosulfate (0.5 g / 100 ml), dioxidine (0.5 g / 100 ml), dimethyl sulfoxide and distilled water (Veterinary preparations in Russia. Handbook. M., 2004. - Part 1 - S.478-479).

The disadvantage of the diometer is a decrease in its therapeutic effectiveness, associated with the development of resistance of microorganisms to the active components of the drug. In addition, the antibiotic kanamycin monosulfate, which is part of the diometer, is excreted in milk, which can negatively affect the health of people who eat it.

The technical result of the invention is the expansion of the spectrum of action and increased antimicrobial activity.

This goal is achieved by the use of a complex preparation consisting of norfloxacin, dioxidine, dimethyl sulfoxide and distilled water, by introducing it into the uterine cavity in cows and post-partum endometritis sick cows and sows with metritis-mastitis-agalactia for therapeutic purposes and after calving and farrowing animals for preventive purposes.

One of the measures preventing the development of resistance of microorganisms is the development of dosage forms that include several components with different mechanisms of antimicrobial action. In the case when the combination of antibiotics does not lead to a synergistic effect, but is limited by an adaptive effect, the spectrum of action of complex drugs expands, which is important for mixed infections. The complex use of antibiotics is also effective when exposed to resistant forms of microorganisms. In this case, various mechanisms of action on the microbial cell are used. Combined antimicrobial therapy reduces the possibility of drug resistance of microorganisms.

Due to the mutually reinforcing effect of the components of complex preparations and the achievement of a therapeutic effect in smaller doses, it becomes possible to reduce the toxicity of individual components.

In connection with the foregoing, the composition for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows includes norfloxacin and dioxidine, which have a wide spectrum of antimicrobial activity, as active components.

The drug for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows consists of the following components, wt.%:

Norfloxacin - 0.4-1.0;

Dioxidine - 0.5-0.9;

Dimethyl sulfoxide - 30-40;

Distilled water is the rest.

Dioxidine 0.5% concentration was chosen because below 0.5% dioxidine solution does not have a pronounced antimicrobial effect, and concentrations above 0.9% do not lead to a significant increase in antimicrobial activity.

Norfloxacin below 0.4% has low antimicrobial activity, and above 1% it has a toxic effect.

Dimethyl sulfoxide below 30% concentration does not have transport functions, and above 40% it reduces the solubility of active components (norfloxacin, dioxidine).

Norfloxacin belongs to the group of vtorhinolones derived from naphthyridine nalidixic acids. As a gyrase inhibitor, it acts on bacterial DNA synthesis, has a wide spectrum of antimicrobial activity and is active against gram-positive and gram-negative microorganisms (Escherichia, staphylococcus, pasteurella, salmonella, mycoplasma and others) (Veterinary preparations in Russia, Handbook, Part 1. Moscow, 2004, . - S.223).

Dioxidine is a quinoxaline drug - 1,4-di-N-oxide-2,3-di (oxymethyl) quinoxaline. Dioxidin exhibits high antimicrobial activity against gram-negative and gram-positive microorganisms. Gram-negative microorganisms are most affected by dioxidine / Chervyakov D.K. et al. Medicines in veterinary medicine. - M .: Kolos, 1977, p. 215 /.

Dimethyl sulfoxide (DMSO) is used as a solvent. It is the only low-toxic substance with the ability to penetrate intact tissues and carry dissolved medicinal substances (penetrating and transport properties) / Dimethyl sulfoxide pharmacology, application in dermatology and related specialties. Perm, 1975 /.

The drug for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows is administered to cows intrauterine using a Janet syringe, with a therapeutic purpose 3-4 times, the first two times at a dose of 200 ml, and then 150 ml, with 48 - an hour-long interval until recovery, for prophylactic purposes, once - at a dose of 200 ml immediately after the operative separation of the placenta or 6-12 hours after a normal birth in cases of wide spread of this pathology in the household; in sows, the drug is administered intrauterine using a device for artificial insemination of pigs - POS-5, for treatment once at a dose of 0.7 ml / kg body weight, if necessary, re-administered after 24 hours, for prevention, the dose is 0.5 ml / kg body weight 6-12 hours after farrowing, once.

The drug is made as follows. Dioxidine and norfloxacin are dissolved in 10% distilled water, the required amount of dimethyl sulfoxide and distilled water are added to 100%.

Quality indicators were studied in three experimental batches of the drug during storage for one year. It was found that during storage of the drug for one year, quality indicators (appearance, transparency, color, authenticity, mass fraction of norfloxacin, dioxidine, microbiological purity, mechanical inclusions) meet the requirements of technical conditions.

The effectiveness of the drug was tested on cows of LLC Voronezhpishcheproduct of the Novousmansky district of the Voronezh region and sows of the pedigree farm company ZAO Krasnodonskoye in the Ilovlinsky district of the Volgograd Region.

Example 1

In order to determine the effectiveness and optimal ratio of the components of the drug for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows, three formulations were compiled.

No. 1 contains, wt.%:

Norfloxacin - 0.4,

Dioxidine - 0.5,

Dimethyl sulfoxide - 30,

Distilled water is the rest.

No. 2 contains, wt.%:

Norfloxacin - 0.75,

Dioxidine - 0.75,

Dimethyl sulfoxide - 35,

Distilled water is the rest.

No. 3 contains, wt.%:

Norfloxacin - 1.0,

Dioxidine - 0.9,

Dimethyl sulfoxide - 40,

Distilled water is the rest.

The experiment was carried out on cows of red-motley breed 4-6 years of age. The diagnosis was made on the basis of a clinical, obstetric and gynecological examination, anamnesis.

The drug was injected into the uterine cavity using a Janet syringe for the first two times at a dose of 200 ml, and then 150 ml at a 48-hour interval until clinical recovery.

Animals of the control group were treated using the base drug - neofur. A neofur suspension prepared at the rate of 3-4 suppositories per 150-200 ml of distilled water was administered at a 48-hour interval until recovery in accordance with the instructions for the drug (Chervyakov D.K. et al. Medicines in veterinary medicine. - M .: Kolos, 1977 .-- P.342).

The animals underwent daily clinical observation, taking into account the time the clinical signs of the disease disappeared, the number of animals recovered and fertilized, the rate of fertilization, and the length of time from calving to fertilization.

Table 1 Therapeutic efficacy of the claimed and known drugs in the treatment of endometritis in cows Indicators Claimed drug Basic version No. 1 Number 2 Number 3 Number of animals, goal fifteen eighteen fifteen fifteen Recovery time, days 15.2 ± 0.62 11.7 ± 0.54 14.5 ± 0.58 15.4 ± 0.96 The number of drug injections 5.09 ± 0.48 3.72 ± 0.34 4.65 ± 0.43 6.21 ± 0.53 Recover, goal 10 16 eleven 9 Therapeutic efficacy,% 66.7 88.9 73.3 60.0 The period from calving to fertilization, days 82.3 ± 7.88 72.3 ± 4.21 78.4 ± 6.71 89.7 ± 6.15 Fertilized at the first insemination,
Goal,
% 8
53.3 13
72,2 9
60.0 7
46.7 Fertilization rate 1.96 ± 0.19 1.68 ± 0.17 1.79 ± 0.09 2.24 ± 0.24 Toxic effect, goal 0 0 0 0

From table 1 it follows that the best therapeutic effect is achieved when applying the composition of the active ingredients No. 2.

Example 2

In order to determine the effectiveness and optimal ratio of the components of the drug for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows, three formulations were compiled.

No. 1 contains, wt.%:

Norfloxacin - 0.4,

Dioxidine - 0.5,

Dimethyl sulfoxide - 30,

Distilled water is the rest.

No. 2 contains, wt.%:

Norfloxacin - 0.75,

Dioxidine - 0.75,

Dimethyl sulfoxide - 35,

Distilled water is the rest.

No. 3 contains, wt.%:

Norfloxacin - 1.0,

Dioxidine - 0.9,

Dimethyl sulfoxide - 40,

Distilled water is the rest.

The experiment was carried out on cows of red-motley breed 4-6 years of age. Prevention of postpartum endometritis was carried out by a single intrauterine injection of the drug using a Janet syringe immediately after surgical separation of the placenta or 6-8 hours after normal delivery at a dose of 200 ml.

The animals of the control group using the basic version were once intrauterine injected with a neofur suspension in a dose of 200 ml immediately after surgical separation of the placenta or 6-8 hours after normal delivery (Chervyakov D.K. et al. Medicines in veterinary medicine. - M .: Kolos, 1977, p. 342).

Animals of the control group without the use of the prototype, no drugs were administered after calving.

The animals underwent daily clinical observation, taking into account the incidence of cows with postpartum endometritis, the percentage of fertilized animals, the period from calving to fertilization, and the fertilization rate.

From table 2 it follows that the best preventive effect is achieved when applying the composition of the active components No. 2.

table 2 The effectiveness of the claimed and known drugs for the prevention of postpartum endometritis in cows Indicators Claimed drug Using the base case Without the use of the drug No. 1 Number 2 Number 3 Number of animals, goal 10 10 13 eleven 10 Got postpartum endometritis Goal, 3 one 2 four 8 % 30,0 10.0 15.4 36,4 80.0 Preventive efficacy,% 70.0 90.0 84,4 63.6 20,0 The period from calving to fertilization, days 60.2 + 4.15 52.3 + 5.12 56.8 ± 4.17 62.1 ± 5.34 69.3 + 7.26 Fertilized at the first insemination, Goal, 5 7 8 5 2 % 50,0 70.0 61.5 45.5 20,0 Fertilization rate 1.72 ± 0.09 1.56 ± 0.1 1.64 ± 0.08 1.91 ± 0.08 2.01 + 0.2 Toxic effect, goal 0 0 0 0 0

Example 3

In order to determine the effectiveness and optimal ratio of the components of the drug for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows, three formulations were compiled.

No. 1 contains, wt.%:

Norfloxacin - 0.4,

Dioxidine - 0.5,

Dimethyl sulfoxide - 30,

Distilled water is the rest.

No. 2 contains, wt.%:

Norfloxacin - 0.75,

Dioxidine - 0.75,

Dimethyl sulfoxide - 35,

Distilled water is the rest.

No. 3 contains, wt.%:

Norfloxacin - 1.0,

Dioxidine - 0.9,

Dimethyl sulfoxide - 40,

Distilled water is the rest.

The experiment was conducted on sows of large white breed in 2-5 farrowing with a body weight of 180-230 kg. Prevention of metritis-mastitis-agalactia was carried out by a single intrauterine injection of the drug using POS-5 4-6 hours after farrowing at a dose of 0.5 ml per 1 kg of body weight.

The animals of the control group, using the basic version, were once intrauterine injected with a neofur suspension prepared at the rate of 1 suppository per 50 ml of distilled water 4-6 hours after farrowing.

Animals of the control group without the use of the prototype, no preparations were administered after farrowing.

The animals underwent a daily clinical examination, taking into account the incidence of sows with metritis-mastitis-agalactia and endometritis.

From table 3 it follows that the best preventive effect is achieved when applying the composition of the active components No. 2.

Table 3 The effectiveness of the claimed and well-known drugs for the prevention of metritis-mastitis-agalactia in sows Indicators Claimed drug Using the base case Without the use of the drug No. 1 Number 2 Number 3 The number of animals in the experience eighteen 19 twenty fourteen 17 Endometritis, goal. four four 5 four 8 % 22.2 21.1 20,0 28.6 47.1 MMA goal 3 2 3 2 four % 16.7 10.5 15.0 14.3 23.5 Healthy goal. eleven 13 12 8 5 % 61.1 68,4 60.0 57.1 29.4

Example 4

In order to determine the effectiveness and optimal ratio of the components of the drug for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows, three formulations were compiled.

No. 1 contains, wt.%:

Norfloxacin - 0.4,

Dioxidine - 0.5,

Dimethyl sulfoxide - 30,

Distilled water is the rest.

No. 2 contains, wt.%:

Norfloxacin - 0.75,

Dioxidine - 0.75,

Dimethyl sulfoxide - 35,

Distilled water is the rest.

No. 3 contains, wt.%:

Norfloxacin - 1.0,

Dioxidine - 0.9,

Dimethyl sulfoxide - 40,

Distilled water is the rest.

The experiment was conducted on pigs of large white breed in 2-4 farrowing. The diagnosis was made on the basis of a clinical, obstetric and gynecological examination.

The drug was injected into the uterine cavity using POS-5 at a dose of 0.7 ml / kg body weight in the form heated to 40 ° C. If the effect after administration of the claimed drug is not obtained, then the drug was re-administered.

Animals of the control group were treated using the base drug neofur. A neofur suspension, prepared at the rate of 1 suppository per 50 ml of distilled water, was administered at a 24-hour interval until recovery in accordance with the instructions for the drug / Chervyakov D.K. et al. Medicines in veterinary medicine. - M .: Kolos, 1977, p.342 /.

The animals underwent daily clinical examination, taking into account the time of disappearance of the clinical signs of the disease (temperature, pulse, respiration, excretion from the external genitalia, general condition, intake of feed and water, the condition of piglets).

Table 4 Therapeutic efficacy of the claimed and known drugs in the treatment of metritis-mastitis-agalactia in sows Indicators Using the base case Using the claimed drug No. 1 Number 2 Number 3 The number of sick animals fourteen twenty 19 twenty Therapeutic effect after a single intrauterine injection 2 (14.3%) 12 (57.8%) 14 (75.0%,) 14 (68.0%) Therapeutic effect after repeated administration to non-recovered animals 10 (71.4%) 16 (80.0%) 17 (91.7%) 19 (95.0%) Did not recuperate after double administration 4 (28.6%) 4 (20.0%) 2 (8.3%) 1 (5.0%) Affected shares mol. sow glands after 5 days from the start of treatment (%) 27.3 23,4 0.7 13,2

From table 4 it follows that the best therapeutic effect is achieved when using the composition of the active ingredients No. 2.

Example 5

To test the antimicrobial activity of the claimed drug in comparison with the prototype, an experiment was conducted. Antimicrobial activity was determined (BS - bacteriostatic activity, BC - bactericidal activity) of the claimed drug by serial dilution method.

Table 5 Antimicrobial activity of the claimed and known drugs Culture The concentration of the drug, mcg / ml diometer claimed drug BS Bts BS Bts Staph. aureus 0.015 0,031 0.0019 0.0078 E.coli 866 0.015 0,062 0,00097 0.0019 E. coli O 33 0.015 0.015 0.0039 0.0078 E.coli O 127 0,031 0,062 0.0039 0.0078 Str. porcinius 0,031 0.124 0.0039 0.015

From table 5 it follows that the claimed drug has a higher antimicrobial activity compared with a diometer.

Example 6

To determine the sensitivity of microflora isolated from the uterine cavity of patients with endometritis of cows and sows to the claimed preparation and diometer, an experiment was conducted. The sensitivity of the selected microflora is determined using indicator discs.

Table 6 The sensitivity of microflora to the claimed drug and diometer Culture Zone of growth inhibition, mm diometer claimed drug E. coli 866 12 16 E. coli O 33 7 23 E. coli O 127 17 19 Staph. aureus 12 21 Staph. epidermidis fifteen 24 Str. agalactiae 9 17 Str. porcinius fifteen 26 Note: with a growth inhibition zone of less than 10 mm, microorganisms are considered insensitive, with a growth inhibition zone of 10 to 15 mm - insensitive, from 15 to 20 mm - sensitive and more than 20 mm - highly sensitive.

From table 6 it follows that the claimed drug has a wider spectrum of antimicrobial action, since in relation to it, almost all the isolated microorganisms show high sensitivity.

Thus, the study showed that a complex preparation consisting of norfloxacin, dioxidine, dimethyl sulfoxide and distilled water expands the spectrum of action in the treatment and prevention of acute postpartum endometritis in cows and metritis-mastitis agalactia in sows and has high antimicrobial activity.

Claims (1)

A drug for the treatment and prevention of postpartum endometritis in cows and metritis-mastitis agalactia in sows, including dioxidine, dimethyl sulfoxide and distilled water, characterized in that it additionally contains norfloxacin in the following ratio, wt.%: norfloxacin 0.4-1.0 dioxidine 0.5-0.9 dimethyl sulfoxide 30-40 distilled water the rest.