RU2746297C1 - Method for the treatment of acute postpartum endometritis in cows - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to veterinary medicine, and for the treatment of acute postpartum endometritis in cows. For this, a complex treatment is carried out, including intramuscular administration on days 1, 2 and 3 of immunocorrecting agents -α, γ-interferons and aminoseleton - with an interval of 24 hours at a dose of 5.0 ml each in combination with the myotropic drug uteroton intramuscularly on days 1-4 at a dose of 10 ml/animal with a 24-hour interval and an etiotropic drug nioxityl intrauterinely at a dose of 10-15 ml/100 kg of body weight with a 48-hour interval.

EFFECT: such a comprehensive pharmacological effect in the specified mode provides effective treatment of endometritis and a decrease in the duration of infertility due to an increase in the general nonspecific resistance of the body and a decrease in microbial contamination of the uterus.

1 cl, 2 ex, 3 tbl

Description

The invention relates to the field of veterinary medicine, in particular to veterinary obstetrics, and can be used for the treatment of acute postpartum endometritis in cows.

Acute postpartum endometritis, diagnosed in 40-70% of fresh cows, continues to be the most significant problems in dairy farming and veterinary obstetrics. This pathology can cause a violation of reproductive function, a decrease in productivity, as well as increase the cost of conducting therapeutic measures, which entails large economic losses. Postpartum endometritis is inflammation mainly of the uterine mucosa. Depending on the nature of inflammation, postpartum endometritis is subdivided into catarrhal, purulent-catarrhal and fibrinous [Nezhdanov AG, Shabunin SV, Mikhalev VI, Filin VV, Skorikov VN. Postpartum metritis in dairy cows // Veterinary medicine. - 2016. - No. 8. - P.4 - 10].

The main method of therapy for acute postpartum endometritis is antibiotic therapy. However, the unreasonably widespread use of antibiotic drugs causes an accelerated selection of drug-resistant populations of pathogenic microorganisms and an increase in the pathogenic action of infectious agents [Ilyinsky, E.V. On some consequences of drug therapy used in obstetric and gynecological practice // Abstracts of the international conference. - Riga, 1997. - P.68-70].

Recently, immunomodulators have been increasingly used for the treatment of postpartum endometritis in cows. This is due to the growing resistance of opportunistic microflora to etiotropic drugs observed in recent decades, an increase in the number of chronic and recurrent forms of inflammatory diseases, as well as the evidence-based immunosuppressive effect of a number of viral pathogens [IV Zvezdochkina. Bernikova A.S., Arinenko R.Yu., Anikin V.B. The use of Viferon in the treatment of chronic urogenital infections // New prospects for the use of interferon preparations in pediatrics and gynecology. Sat. scientific. works. - St. Petersburg, 1997. - P.4-5].

In this regard, one of the mechanisms for increasing the effectiveness of therapeutic measures in acute postpartum endometritis in cows is an increase in the general and local resistance of the body through the use of general stimulating agents.

A known method for the treatment of acute postpartum endometritis in cows, providing for three times the introduction of the drug, the placenta denatured emulsified on the 1st, 5th and 9th day subcutaneously at a dose of 5 ml / 100 kg of body weight, 15% solution of ASD-2F on trivitamin intramuscularly at a dose of 10 ml in 1, 3 and 5 days of treatment in combination with injections of a 2% oily solution of sinestrol at a dose of 0.6 ml / 100 kg of body weight on days 1 and 2 and the introduction of oxytocin at a dose of 10 U / 100 kg of body weight from the 2nd on the 5th day, as well as a tetrameter intrauterinely, starting from the 1st day, at a dose of 150 ml twice with an interval of 48 hours and then - 100 ml each. With this method of treatment, clinical recovery was registered in 86.7% of animals [Chupryn S.V. Complex therapy of cows with postpartum endometritis / S.V. Chupryn and V.I. Mikhalev // Veterinary Medicine. - 2011. - No. 2. - S.48-50].

The disadvantage of this method of therapy for postpartum endometritis in cows is its insufficiently high therapeutic efficacy, laboriousness of injection of a placental preparation in the form of an emulsion.

A known method of treating acute postpartum endometritis in cows using an extract of the placenta of cows with specific bacteriophages (staphylococcal, streptococcal, Proteus, enteropathogenic strains of Escherichia coli and pasteurellosis). The drug is injected into the ischio-rectal fossa, into loose connective tissue to a depth of 3-5 cm at the rate of 0.1 ml per 1 kg of animal body weight every 48 hours 5-6 times. This method provides a clinical recovery of 84.9% of animals [RU 2129000 C1, A61K 35/50, A61K 35/66, published 20.04.1999].

The disadvantage of this method of therapy is laboriousness. In addition, repeated injections can cause tissue infiltration and edema at the injection site, which can further impede drug administration.

The closest technical solution, taken as a prototype, is a method of treating postpartum endometritis in cows, which provides for three times administration of bovine recombinant α-, γ-interferons at a dose of 5.0 ml each with a 24-hour interval in combination with a myotropic (intramuscular uteroton in the first 4 days at a dose of 10 ml / animal with a 24-hour interval) and an etiotropic drug (nioxityl intrauterinely at a dose of 10-15 ml / 100 kg of body weight with a 48-hour interval) [RU 2704979 C1, A61K 38/21, A61K 31 / 138, A61K 31/47, A61K 31/498, A61K 31/65, A61P 15/00, 01.11.2019 Byull. No. 31].

However, this method of treating postpartum endometritis in cows has insufficiently high therapeutic efficacy.

The invention solves the problem of increasing the effectiveness of therapy for postpartum endometritis in cows. The achieved technical result is a decrease in the duration of infertility and the fertilization rate, an increase in the general nonspecific resistance of the organism, a decrease in microbial contamination of the uterus.

The technical result is achieved by the fact that in the method of treatment of acute postpartum endometritis in cows, including intramuscular administration on days 1-2-3 of immunocorrective agents of α- and γ-interferons with an interval of 24 hours at a dose of 5.0 ml of each in combination with the myotropic drug Uteroton intramuscularly on days 1-4 at a dose of 10 ml / animal with a 24-hour interval and an etiotropic drug nioxityl intrauterinely at a dose of 10-15 ml / 100 kg of body weight with a 48-hour interval, according to the invention, aminoseleton is additionally used intramuscularly in 1, 2 and 3 days with an interval of 24 hours at a dose of 5.0 ml / animal.

Aminoseleton is a tissue preparation obtained from the spleen by cryofractionation. This drug is used for immunodeficiency states of various etiologies. It is known that biologically active substances that increase cellular and humoral immunity are contained in the organs of the immune system of animals, including the spleen. The cells of this organ produce opsonins (tuftsin, fibronectin, etc.,) a large complex of cytokines (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-18, TNF, granulocyte-macrophage colony-stimulating factor, IFN-α, IFN-γ) vasoactive intestinal peptide, hepatocyte growth factor or scattering factor - HGF / SF, spleen-derived growth factor - SDGF [RU 2538721 C1 , A61K 31/00, A61K 35/12, A61K 35/28, A61P 15/00, 01/10/2015 Bull. No. 1].

Bovine recombinant interferon is a species-specific drug that exhibits immunostimulating and antiviral activity in cattle. The effect of the drug is determined by the total action of the exogenous protein and the rapid induction of the endogenous interferon system, cellular and humoral immunity. Bovine recombinant interferon acts as an inducer of lysozyme and bactericidal activity of blood serum. Has anti-inflammatory effect. Increases the resistance of the animal body to the effects of DNA and RNA-containing viruses and pathogenic microorganisms [Instructions for use of the veterinary preparation "Interferon bovine recombinant IBR". Registration certificate No. 4950-10-15 BPH-F from 15.07.15].

Uteroton consists of propranolone hydrochloride as active ingredient, citric acid, chloroetone and sodium metabisulfite as preservatives, and water for injection. 1 ml of uteroton contains 5% propranolone hydrochloride. Uteroton has a blocking effect on the beta-adrenergic receptors of the myometrium, which contributes to the manifestation of the activity of endogenous oxytocin, as a result of which the contractions of the smooth muscles of the uterus and mammary gland increase. Uteroton is used to stimulate labor, atony, hypotonia of the uterus, treatment and prevention of retention of the placenta, subinvolution of the uterus, postpartum endometritis in cows and the syndrome of "metritis-mastitis-agalactia" in sows, increasing fertility, removing embryos from donor cows. Uteroton is administered intramuscularly or intravenously at a dose of 10 ml per cow and 5 ml per sow [Instructions for the use of the drug uterotong to stimulate labor, treatment and prevention of gynecological diseases in cows and metritis-mastitis-agalactia syndrome in sows. Registration certificate number 44-3-10.17-3857 No. PVR-3-5.0 / 00530 dated 29.08.2017].

Nioxityl suspension contains 0.01 g of oxytetracycline hydrochloride, 0.01 g of tylosin tartrate, 0.04 g of nitroxoline, and up to 1 ml of excipients in 1 ml of oxytetracycline hydrochloride. Tylosin tartrate, oxytetracycline hydrochloride and nitroxoline, which are part of the drug, have a pronounced antimicrobial effect on a wide range of gram-positive and gram-negative microorganisms, including anaerobes, as well as fungi. The mechanism of action of oxytetracycline hydrochloride is to inhibit protein synthesis of microorganisms on ribosomes, causing a bacteriostatic effect, nitroxoline - in violation of the permeability of a microbial cell for metal ions, being a hydrogen acceptor, disrupts cellular respiration of microorganisms and their enzymatic functions. Suspension "Nioxityl" is used in cattle for the treatment and prevention of endometritis. The drug is administered for therapeutic purposes in utero at a dose of 10-15 cm ^3/100 kg of animal weight using Janet syringe, with an interval of 48-72 hours prior to recovery, with the preventive - once, after separation of the placenta at 10 cm ^3/100 kg of animal weight [Instructions for the use of the suspension "Nioxityl". Approved by the Veterinary and Pharmaceutical Council under the Department of Veterinary and Food Control of the Ministry of Agriculture and Food Industry of the Republic of Belarus dated 15.07.13, Protocol No. 67].

The essence of the technical solution of the invention is illustrated by examples.

Example 1. The study of the effectiveness of the proposed method of treatment of acute postpartum endometritis in cows was carried out on 20 animals, divided according to the principle of analogues into two groups.

Animals of the first group (n = 10) were injected three times in 1-2-3 days with α-, γ-interferons at a dose of 5.0 ml in combination with myotropic (intramuscular uteroton in the first 4 days at a dose of 10 ml / animal with 24 hour interval) and etiotropic drug (nioxityl intrauterinely at a dose of 10-15 ml / 100 kg of body weight with a 48-hour interval).

The cows of the second group (n = 10) were injected three times in 1-2-3 days with α, γ-interferons at a dose of 5.0 ml / animal and aminoseleton at a dose of 5.0 ml / animal in combination with myotropic (intramuscular uteroton in the first 4 days at a dose of 10 ml / animal with a 24-hour interval) and an etiotropic drug (nioxitil intrauterinely at a dose of 10-15 ml / 100 kg of body weight with a 48-hour interval).

The animals were subjected to daily clinical examination. The time of disappearance of clinical signs of the disease, the number of recovered animals, the number of intrauterine injections of the antimicrobial drug, the results of insemination and fertilization, and the duration of the period from calving to fertilization were taken into account.

The results of the studies are presented in table 1.

From the data shown in Table 1, it follows that the complex treatment of cows with acute postpartum endometritis using the prototype is accompanied by the recovery of 90.0% of animals with 5.67 intrauterine administration of the antimicrobial drug nioxityl. The most effective treatment was using the proposed method, accompanied by clinical recovery of 100.0% of animals, which is 10.0% more compared to the animals of the prototype group, while reducing the number of intrauterine injections of nioxityl by 0.26 times. Fertilization rate after treatment using the proposed method of therapy is less by 0.4 in comparison with the prototype, and the period from calving to fertilization is 13.7 days, respectively.

The high therapeutic efficiency of the proposed method of treatment is ensured by increasing the indices of the humoral and cellular links of general nonspecific resistance while reducing inflammatory processes in the organs of the reproductive system and the degree of their microbial contamination (example 2, tables 2, 3).

Example 2. Before and after treatment, blood samples were taken for immunological and biochemical studies. The results are shown in Table 2.

In the group of cows after treatment with the use of the prototype, a decrease in the blood content of leukocytes by 17.6% was found, including eosinophils - by 34.5%, stab neutrophils - by 11.8%, monocytes - by 25.9%, average molecular peptides (SMP) - by 28.1%, average weight molecules (MSM) - by 21.2%, stable nitric oxide metabolites (NO _x ) - by 26.0%, endogenous intoxication index (IEI) - by 16.1 %, with an increase in the concentration of vitamin A by 1.5 times, vitamin E - by 37.5% o, catalase activity - by 18.0% and glutathione peroxidase - by 22.5%.

In the group of cows after treatment using the proposed method, more pronounced changes in the morphological and immuno-biochemical status of animals were noted, indicating a decrease in the inflammatory process in the uterus, the intensity of lipid peroxidation, activation of the humoral and cellular links of immunity, enzymatic and non-enzymatic links of antioxidant protection. When using the proposed method of treatment of acute postpartum endometritis, a decrease in the concentration of leukocytes by 42.3%, eosinophils - by 2.05 times, stab neutrophils - by 20.6%, monocytes - by 1.5 times, circulating immune complexes - by 28 was noted, 0%, malondialdehyde - by 28.7%), average weight molecules - by 27.3%, SMP - by 39.7%, endogenous intoxication index - by 24.4%, stable nitric oxide metabolites - by 39.9 %, with an increase in the content of lymphocytes by 6.9%, total protein - by 14.9%, vitamin A - 1.9 times, vitamin E - 1.5 times, vitamin C - by 29.6%, BASK - by 11.2%, PAL - by 14.3%), catalase activity - by 21.7%, glutathione peroxidase - by 34.1%.

Before treatment and at the end of the therapeutic course, samples of the contents of the uterus were taken for bacteriological studies (the degree of microbial contamination and the species composition of the microflora). The results are shown in Table 3.

It was found that the therapy of acute postpartum endometritis in cows using the prototype is accompanied by a decrease in the total microbial contamination of the uterus of cows by 7.05 times. The microflora of the uterine contents of cows after a therapeutic course with the use of α-, γ-interferons is represented by E. coli - 10.0%) cases, Proteus. vulgaris - 10.0%, Ent. faecium -10.0%, indicating incomplete sanitation of the uterine cavity during treatment.

After complex treatment of cows using the proposed method, the degree of microbial contamination of the uterus was 219.7 ± 26.5 CFU / ml, which is 12.0 times less compared to sick animals and 1.7 - than in animals of the prototype group. Representatives of the indigenous normal microflora of the mucous membranes, Ent. faecium - 10.0% and Ent. faecalis - 10.0%, which confirms the clinical efficacy of the treatment.

Claims (1)

A method of treating acute postpartum endometritis in cows, including intramuscular administration on days 1, 2 and 3 of immunocorrecting agents α- and γ-interferons with an interval of 24 hours at a dose of 5.0 ml each in combination with the myotropic drug uteroton intramuscularly on days 1-4 in a dose of 10 ml / animal with a 24-hour interval and an etiotropic drug nioxityl intrauterinely at a dose of 10-15 ml / 100 kg of body weight with a 48-hour interval, characterized in that, as an immunocorrective agent, aminoseleton is additionally used intramuscularly in 1, 2 and 3 days with an interval of 24 hours at a dose of 5.0 ml / animal.