RU2287329C1 - Method for treating puerperal purulent-catarrhal endometritis and mastitis in cows and method for its application - Google Patents

Abstract

FIELD: veterinary science.

SUBSTANCE: the present innovation refers to medicinal preparations applied for treating puerperal purulent-catarrhal endometritis and mastitis in cows and to the method of applying the present medicinal preparations. The suggested preparation for treating puerperal purulent-catarrhal endometritis, serous, seroso-catarrhal and subclinical mastitis in cows includes 1.4-di-N-oxide 2.3-bis-(oxymethyl) quinoxaline, trecresan (cresacin), dimethyl sulfoxide, propandiol 1.2 at the following ratio, (g/%): 1.4-di-N-oxide 2.3-bis-(oxymethyl) quinoxaline 1.0-1.2; trecresan (cresacin) 3.0-3.18; dimethyl sulfoxide 10.0-10.5; propandiol 1.2 20-25; distilled water - the rest. The innovation deals with intra-uterine introduction of the preparation suggested at the dosage of about 70-100 ml once daily for about 4-5 d. Moreover, this preparation should be introduced into affected part of the udder at the dosage of 10 ml once daily for 3-5 d. The innovation enables to shorten the multiplicity of introduction and accelerate the terms of recovery.

EFFECT: higher efficiency of therapy.

4 cl, 2 ex, 6 tbl

Description

The invention relates to veterinary medicine, namely to medicines used for the treatment of postpartum purulent-catarrhal endometritis and mastitis in cows and methods of using these drugs.

A known drug and method for the treatment of serous mastitis in cows with masticide (Veterinary law. - M .: Kolos, 1981. - S.327-328). The drug contains penicillin, streptomycin, sulfadimezin and norsulfazole, suspended in vegetable oil. The drug is administered for two to three days, twice a day every 12 hours.

A known method of treatment with mastisan E (Obstetrics, gynecology and biotechnology of reproduction. - M .: Kolos, 2000. - P.327). The drug contains erythromycin base, sulfadimezin and an oil base. 5-10 ml are injected into the nipple udder twice a day for 2-3 days.

The disadvantages of these drugs and methods of their use include a relatively low therapeutic and prophylactic effect, the possibility of developing antibiotic resistance, long waiting times for the use of milk for food (4-6 days after the last injection), significant labor and material costs.

Closest to the proposed and adopted as a prototype is dioxidine 1% solution and method of its use (Veterinary medicine. 2004. No. 9; RU 2228176 C2). The composition of the drug includes 1,4-di-N-oxide 2,3 bis- (oxymethyl) quinoxaline, a preservative and water for injection. The drug is used to treat clinical and subclinical forms of mastitis and for prophylactic sanitizing treatment of the udder at the beginning of the dry period. Depending on the indications, the drug is injected into the nipple of the udder in doses of 10 to 30 ml twice a day for 2-4 days. The drug is also used to treat endometritis at a dose of 200 ml by injection into pararectal fiber.

The disadvantages of this drug and its use include the absence of a prolonging effect, the instability of the dosage form, which does not exclude additional manipulations before administration (heating in a water bath until the precipitate dissolves when the drug is stored below 15 ° C), significant material and labor costs excessive trauma to animals.

The technical problem solved by this invention is to expand the range of tools and methods for the treatment of mastitis and endometritis in cows.

The essence of the invention lies in the fact that the preparation for the prevention and treatment of mastitis in cows contains 1,4-di-T-oxide 2,3-bis- (oxymethyl) quinoxaline, propanediol 1,2, dimethyl sulfoxide, methyl para-hydroxybenzoic acid, distilled water and according to the invention, these substances are contained in the following ratio of components, g /%:

1,4-di-N-oxide 2,3-bis- (oxymethyl) quinoxaline 1.0-1.2 trekrezan 3.0-3.18 dimethyl sulfoxide 10.0-10.5 propanediol 1,2 20,0-25 distilled water rest

Dioxidine (1,4-Di-N-oxide 2,3-bis- (oxymethyl) quinoxaline) is a greenish-yellow crystalline powder, odorless, sparingly soluble in water, alcohol, pH of a 1% solution of 5.2-7.2. Refers to antimicrobial agents of a wide spectrum of action. Effective against gram-positive and gram-negative microflora. It acts on bacterial strains resistant to other chemotherapeutic agents, including antibiotics. It is registered in the Russian Federation (per. Certificate No. 76/647/1).

Trekrezan (crezacin, orthocresoxyacetate / 2-hydroxyethyl / ammonium-ammonium salt of orthocresoxyacetic acid) is a crystalline powder with a yellowish, cream or grayish tint, is readily soluble in water, has a specific odor, and is not toxic. Krezacin activates the pituitary-adrenal system, stimulates protein biosynthesis, activates ATPases. It stimulates the humoral response, affects the production of cytokines, erythropoiesis, the functional properties of hematopoietic stem cells, induces the production of interferon, reduces the content of circulating immune complexes, increases Ig G in serum. It is used in animal husbandry as a feed additive as a stimulant of immunity, growth processes, and reproductive function , milk, meat and egg productivity. After using the drug, products are used without limitation. It is registered in the Russian Federation (Per. No. 10.07.173. - 94 ovpp).

Dimethyl sulfoxide is a colorless transparent liquid or colorless crystals (melting at a temperature of + 18.5 ° C.) With a specific smell. Hygroscopic. Miscible in all respects with water and alcohol. It has the ability to penetrate through cell membranes, including through skin barriers. It has analgesic and anti-inflammatory, moderate antiseptic and fibrinolytic effects. Enhances the penetration through the skin of certain medicinal substances. It is registered in the Russian Federation (per. Certificate No. 75/244/9).

Propylene glycol (1,2-propanediol) is a colorless, odorless, viscous liquid with a sweet taste. Miscible with water and alcohol in all ratios. It is used as a plasticizer and solvent for high molecular weight compounds. In veterinary medicine it is used as a solvent and drug prolongator.

The essence of the invention also lies in the fact that in the known method of treatment, including intercisternal administration of the drug, according to the invention, the sick animals are injected with the drug in the nipple of the udder at a dose of 10 ml for three to four days, with an interval of 24 hours.

The invention also lies in the fact that in the known method of treatment, including the intrauterine administration of the drug according to the invention, sick animals are administered the drug in the uterine cavity at a dose of 70-100 ml once a day for 4-5 days, with an interval of 24 hours.

A study of the pharmacokinetic properties found that with intrauterine and intercisternal administration, the drug does not cumulate and is completely excreted after 24-36 hours. Milk can be used in food 24 hours after the last injection.

According to the results of toxicological studies, the drug has low toxicity for animals, does not adversely affect hematological parameters with the recommended methods of administration. LD _{50 of} gynodixin for white mice with intraperitoneal administration is 47.5 ml / kg body weight. It does not cause chronic toxicosis in white rats and cows.

It does not have a sensitizing effect, does not irritate the conjunctiva, vaginal mucosa, endometrium and udder parenchyma.

The drug exhibits an anti-microbial effect against gram-positive and gram-negative microflora and their various associations secreted in mastitis and endometritis. The drug has an uterotonic effect and contributes to the accelerated removal of inflammatory exudate from the uterine cavity.

The therapeutic efficacy of the drug in postpartum purulent-catarrhal endometritis of cows is 94.44%. The drug improves the overall resistance of the body: increasing hemoglobin (by 14.49%), albumin (by 21.18%), the level of phagocytic activity of neutrophils (by 15.55%), lysozyme activity of serum crozi (by 36.47% ) The use of the drug helps to reduce the service period by an average of 19-20 days, increase the number of cows that are fertilized after the first insemination by an average of 29%.

The cost of treatment with the drug is significantly lower than when using other drugs.

The therapeutic effect of the drug with serous and subclinical mastitis is 100%, serous-catarrhal - 89.44%. The effectiveness of the treatment of various forms of mastitis with this drug compared with traditional ones increases by an average of 2-12.5%.

The use of the drug is not accompanied by the development of side effects and complications.

The drug is convenient to use, does not require special preparation before administration. The drug can be simultaneously used in the treatment of endometritis and mastitis in cows.

Using the drug and the specified method of treatment can reduce the risk of local dysbiosis.

The drug is prepared in a weight-volume manner under aseptic conditions in a specially equipped room. Propanediol 1.2 is poured into the prepared container in an amount of 20.0-25.0 g /%, dimethyl sulfoxide - 10.0-10.5 g /%. Heated to 75-82 ° C, loaded with dioxidine 1.0-1.2 g /%, stirred until complete dissolution, add 1/2 of the required volume of distilled water, mixed. Then make trekrezan (crezacin) 3.0-3.18 g /%, mix until completely dissolved and the volume is adjusted with distilled water.

The finished dosage form of the drug is a light yellow transparent solution with a pH of 6.5-7.5. Available in glass bottles for running in capacity of 10 ml, 100 ml, 400 ml.

Depending on the disease, the drug is used by intercisternal or intrauterine route of administration. With postpartum purulent-catarrhal endometritis, the drug is administered into the uterine cavity at a dose of 70-100 ml once a day for 4-5 days, with an interval of 24 hours.

With mastitis, the drug is administered after thorough secretion from the affected lobe and disinfection of the nipple. Introduced in a dose of 10 ml once a day for three to four days, with an interval of 24 hours.

Example 1. The study of the effectiveness of the drug in postpartum purulent-catarrhal endometritis of cows was carried out in one of the farms of the Novosibirsk region. Sick cows were divided into experimental and control groups of 36 and 20 cows. The animals of the experimental group were intrauterine injected with the drug in a dose of 100 ml once a day for 4-5 days. The composition of the drug is as follows, g /%: 1,4-di-N-oxide 2,3-bis- (oxymethyl) quinoxaline - 1.0-1.2; trekrezan (crezacin) 3.0-3.18; dimethyl sulfoxide - 10.0-10.5; propanediol 1.2-20-25; distilled water the rest.

The furapen was used in the animals of the control group according to the instructions for its use. Before treatment and five days after the experiment, blood samples and vaginal mucus were taken from laboratory animals for 5 animals from the control and experimental groups.

Comparative therapeutic efficacy in relation to the prototype (1% dioxidine solution) was carried out according to the main indicators shown in table 3.

It was found that endometritis is mainly observed in cows on the 7-10th day after calving and manifests itself in the form of abundant uterine-vaginal discharge of grayish-white color with an admixture of pus, in some cases the discharge becomes brownish. During rectal examination, the uterine horns are enlarged, fluctuate, and retraction is reduced.

Microbiological analysis of utero-vaginal exudate was predominantly distinguished for streptococci (66.11%), diplococci (41.67%) and staphylococci (33.33). Less commonly, Escherichia cultures (19.44%), Proteus (13.89%), Bacillus subtillis (19.44%), Yersenium (16.67%).

Cytogram of vaginal discharge of cows with postpartum endometritis, leukocyte type, degraded and normal neutrophils in the field of view, significant accumulations of microbes, erythrocytes, single epithelial cells are found.

After drug administration, the clinical picture of the disease changed the next day in 34 cows of the experimental group and was characterized by a sharp increase in the number of secreted lochia. After the second injection of the drug, they stood out in much smaller quantities, became transparent and viscous. On 3-4 days of treatment, utero-vaginal discharge was absent or excreted in small amounts. In the cytogram of secretions on the second day after treatment, the number of degraded neutrophils and focal accumulations of microflora decreased, the number of epithelial cells increased. On the fifth day after treatment, the cytogram was characterized by single clusters of microbes, the appearance of symplasts of keratinizing and non-keratinizing (super-official) epithelial cells and leukocytes.

In the control group, similar changes in the clinic were noted in 17 cows. Three animals had relapses on the third day after treatment. Five days after the course of treatment, neutrophils prevailed in the cytogram of utero-vaginal mucus without signs of degeneration, epithelial superficial cells, accumulations of microbes, and single red blood cells were found.

The comparative effectiveness of the treatment in relation to known methods (furapen) is shown in table 1.

Table 1 No. Indicator Group experienced control goals % goals % one. The number of goals in the group 36 twenty 2. Cows in the group recovered 34 94.44 17 85 3. Fertilized cows,% thirty 88.23 9 52.94 four. Fertilized cows after the first insemination,% 22 64.7 6 35.29 5. The duration of infertility, days 64.62 ± 8.24 84.33 ± 9.15 6. Fertilization index 1,56 2,33 7. Cows were rejected (goal): of all of them: as a result
infertility
abortion
pathology of the musculoskeletal system
four
one
2
one
6
four
2

Morphological and biochemical blood parameters in cows of the experimental and control groups were within the physiological norm (Table 2).

After treatment with the drug, cows showed a significant increase in hemoglobin (by 14.49%), albumin (by 21.18%), the level of phagocytic activity of neutrophils (by 15.55%) and lysozyme activity of blood serum (by 36.47%) . At the same time, the content of α-globulins (by 18.55%) and γ-globulins (by 20.53%) decreased in the blood serum of cows of this group. The level of bactericidal activity of blood serum did not change (table 2).

In the control group of cows, the amount of hemoglobin increased by 8.74%, albumin increased by 4.5%. An increase in the level of bactericidal and lysozyme activity was unreliable. In the control group of animals, a decrease in the content of total protein (by 8.92%), α-globulins (by 6.31%), and γ-globulins (4.09%) was noted.

table 2 Indicator Group experienced Control Hemoglobin, g \ l

*

*

* Red blood cells, 10 ¹² \ l

White blood cells, 10 ⁹ \ l

Total protein, g \ l

*

* Calcium, mg /%

Inorganic phosphorus, mg /%

Alkaline reserve, mg /%

Carotene, mg /%

Vitamin E, mg /%

Albumin,%

Alpha globulins,%

Beta globulins,%

Gamma globulins,%

Lysozyme activity of blood serum. %

Bactericidal activity of blood serum,%

Phagocytic activity,%

* P <0.05, ** P <0.01

The use of this method of treatment contributes to the recovery of animals in 94% of cases. Along with this, the number of days of infertility decreases (on average by 20 days), the fertility of cows from the first insemination increases by 1.8 times in comparison with indicators in cows of the control group.

The drug does not adversely affect hematological parameters, it helps to increase hemoglobin, total protein, increase the level of phagocytic activity of neutrophils and lysozyme activity of blood serum.

Table 3 presents a summary of the therapeutic efficacy of the claimed drug and treatment method, known treatment method (furapen) and prototype.

Table 3 No. Indicator Group a drug prototype experienced control one. The number of goals in the group 36 twenty 22 2. Clinically recovered cows in the group,% 94.44 85 97.46 3. Fertilized cows,% 88.23 52.94 83.33 four. The duration of infertility, days 64.62 ± 8.24 84.33 ± 9.15 84.3 ± 8.0 5. Fertilization index 1,56 2,33 1.7

From the data it follows that the use of the drug can increase the number of fertilized cows in comparison with the prototype by 5.36%, reduce the number of days of infertility by 30.46% (19 days) and improve the fertilization index by 8.97%.

Example 2. Research was conducted on the farms of the Novosibirsk region. The therapeutic efficacy of the drug was determined on sick cows with diagnoses: serous, serous-catarrhal, subclinical forms of mastitis. Animals were formed in six groups (3 experimental, 3 control). The cows of the experimental groups in the amount of 39 were treated with gynodixin, which was introduced into the nipple using a catheter or through a cannula of a glass syringe after preliminary disinfection of the nipple once a day at a dose of 10 ml. The composition of the drug is as follows, g /%: 1,4-di-N-oxide 2,3-bis- (oxymethyl) quinoxaline - 1.0-1.2; trekrezan (crezacin) - 3.0 - 3.18; dimethyl sulfoxide - 10.0-10.5; propanediol 1.2-20-25; distilled water - the rest.

The cows of the control groups in the amount of 33 used intracisternal administration of antibacterial drugs (masticide, mastisan A, mastisan E).

Comparative therapeutic efficacy in relation to the prototype (1% dioxidine solution) was performed according to the main indicators shown in table 6.

To assess the effectiveness of treatment, a clinical examination was carried out, the results of laboratory studies of milk samples (bacteriological study, reaction with a 10% mastidine solution, sedimentation test), the duration of treatment, the cost of acquiring drugs, the frequency of administration of the drug, possible complications, and the number of recovered animals were taken into account. The results of the experiments are presented in table 4.

Table 4 Indicator Forms of mastitis Serous Sero-catarrhal Subclinical experienced control experienced control experienced control Number of cows 9 8 fifteen 10 fifteen fifteen Sick lobes 9 8 19 13 eighteen 17 Cows recovered 9 7 13 8 fifteen fourteen Healed 9 7 17 eleven eighteen 16 Lack of therapeutic effect one 2 2 one Relapse disease one - - Duration of treatment (days) 3.4 3.3 3.68 3.69 2.6 2.75 The effectiveness of the treatment (%) one hundred 87.5 89.44 84.61 one hundred 98

The results of the analysis of blood serum of patients with serous mastitis of cows (Table 5) indicate the correspondence of morphological and biochemical parameters in cows of the experimental and control groups to the physiological norm.

Table 5 Indicator Group experienced control Hemoglobin, g \ l

Red blood cells, 10 ¹² \ l

White blood cells, 10 ⁹ \ l

Total protein, g \ l

Calcium, mg /%

Inorganic phosphorus, mg /%

Alkaline reserve, mg /%

Carotene, mg /%

Vitamin E, mg /%

Albumin,%

Alpha globulins,%

Beta globulins,%

Gamma globulins. %

AlaT

Asat

Urea

* P <0.05, ** P <0.01

As studies have shown, in the serum of cows of the experimental group after treatment, the activity of enzymes (AlaT, AsaT) significantly decreased. A decrease in these indicators indicates a normalization of the indicators of the functional state of the liver and the absence of the cytolytic effect of the drug on hepatocytes.

The therapeutic efficacy in the treatment of serous and subclinical mastitis was 100%, and of serous-catarrhal 89.44%. In the control groups, the indicators were significantly lower and amounted to: in the treatment of subclinical mastitis 98%, serous-catarrhal 84.61%, serous - 87.5%. The effectiveness of the treatment of various forms of mastitis in the experimental groups increased on average by 2-12.5%.

The drug showed a higher therapeutic efficacy compared to the prototype (table 6). The duration of treatment with the drug is on average 1.15 times shorter, and therapeutic efficacy, depending on the form of mastitis, is 2.91-10.75% higher.

Thus, the proposed drug and method for the treatment of mastitis and endometritis in cows is more effective than known.

The technical result solved by the invention is to improve the form of the drug, which does not require additional manipulations before administration (heating to 40 ° C), reducing the frequency of administration and accelerating the healing time, increasing the effectiveness of treatment.

Table 6 Indicator Forms of mastitis Serous Sero-catarrhal Subclinical experienced control prototype experienced control prototype experienced control prototype Number of cows 9 8 9 fifteen 10 8 fifteen fifteen 10 Sick lobes 9 8 10 19 13 8 eighteen 17 10 Cows recovered 9 7 8 13 8 7 fifteen fourteen 7 Healed 9 7 9 17 eleven 7 eighteen 16 7 Lack of therapeutic effect one one 2 2 one 3 Relapse disease one one - - one Duration of treatment (days) 3.4 3.3 4.0 3.68 3.69 4.26 2.6 2.75 3.2 The effectiveness of the treatment (%) one hundred 87.5 89.25 89.44 84.61 86.53 one hundred 98 96.22

Claims (4)

1. The drug for the treatment of postpartum purulent-catarrhal endometritis, serous, serous-catarrhal and subclinical mastitis in cows, including 1,4-di-N-oxide 2,3-bis- (oxymethyl) quinoxaline and water, characterized in that it further includes trekrezan, dimethyl sulfoxide and propanediol 1,2 in the following ratio of components, g /%: 1,4-di-N-Oxide 2,3-bis- (hydroxymethyl) quinoxaline 1.0-1.2 Trekrezan (crezacin) 3.0-3.18 Dimethyl sulfoxide 10.0-10.5 Propanediol 1.2 20-25 Distilled water Rest 2. A method of treating postpartum purulent-catarrhal endometritis, serous, serous-catarrhal and subclinical mastitis in cows, comprising administering the drug, characterized in that the drug is administered according to claim 1 once a day for 3-5 days. 3. The method according to claim 2, characterized in that for the treatment of postpartum purulent-catarrhal endometritis, the drug is administered into the uterine cavity at a dose of 70-100 ml. 4. The method according to claim 2, characterized in that for the treatment of serous, serous-catarrhal and subclinical mastitis, the drug is administered intercisternally into the affected portion of the udder at a dose of 10 ml.