RU2489158C2 - Drug for prevention of endometritis in cows and method for using it - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to veterinary science, particularly to methods and drugs for prevention and treatment of obstetric and gynecological diseases in cows. The agent for prevention of endometritis in cows contains an antimicrobial agent and a base with the antimicrobial agent presented by the above-critical CO₂-marigold extract, while the base is silicone glycerolate - organic-silicon glycerohydrogel that is a water-soluble organic-silicon glycerol derivative possessing transmucous activity with its composition described by formula (CH₃)₂Si(C₃H₇O₃)₂xC₃H₈O₃, in the following relation, wt %: above-critical CO₂ marigold extract - 0.5; organic-silicon glycerohydrogel - up to 100. The drug uses above-critical CO₂-marigold extract produced by Grumant LLC, the Novgorod Region. A method for prevention of endometritis in cows involves the integrated therapy with intra-uterine administration of the above drug cows for 3-5 times every 48 hours, at 100-200 g per one administration, wherein the drug is diluted in sterile water in ratio 1:2 before use.

EFFECT: drug possess a high penetrating effect, the group of inventions provides the more effective prevention of endometritis in cows.

3 cl, 6 tbl

Description

The invention relates to the field of veterinary medicine, in particular to methods and means for the prevention and treatment of obstetric and gynecological diseases in highly productive cows, and can be used both in large livestock complexes, and in farm and personal farms.

It is known to use the foaming preparation Ginobiotik (Ginobiotik) manufactured by LEK, Slovenia, including neomycin and oxytetracycline for the prevention and treatment of postpartum genital infections in cows and pigs. For therapeutic purposes, cows are administered 1-3 tablets weighing 15 grams every 24 hours until recovery, but no more than 5 times (see. Prospectus LEC, Slovenia).

With good results of treatment with this drug, the disadvantage of this method of treatment is the use of potent antibiotics in the preparation, which leads to the need to reject milk within 10 days after the last injection and to loss of production, in addition, this foam form makes it difficult for the active ingredients to penetrate into animal tissue and is long removed from the body of cows.

Also known is the drug enrocid, including enrofloxacin, dimethyl sulfoxide and distilled water, used for the treatment and prevention of postpartum, gynecological diseases in cows and sows. Enrocid is used intrauterine with a Janet syringe to cows in a dose of 100 ml no more than 5 times, after 48 hours in combination with other drugs (see the instruction for the use of the drug Enrocyt ZAO NPP Agrofarm in Voronezh, 2003 No. PVR- 2-0.3 \ 01215).

The disadvantages of the drug include its active mono-composition, which may limit the spectrum of its action in the treatment of animals, while dimethyl sulfoxide, which increases the absorption of the drug, has increased toxicity, an unpleasant odor and can cause allergic reactions in animals and staff.

There is also known “A remedy and method for treating endometritis in cows" in which pefloxacin, metronidazole and chlorhexidine bigluconate are included as active ingredients, and the water-soluble organosilicon compound, a glycerol derivative providing the agent with increased penetrating activity, is used as the active substance (see RF Patent No. 2404756, A61K 31/02, publ. 11/27/2010, bull. No. 33).

With ease of use and high quality of treatment, the use of antibiotics and other chemotherapeutic drugs that limit the consumption of milk obtained from cows during the use of the drug should be attributed to the lack of funds.

The objective of the invention is to develop a wide spectrum of action without the use of antibiotics for intrauterine administration and a method for its use for the prevention of postpartum endometritis in cows, which has not only increased penetration into tissues during intrauterine administration, but also does not cause allergic reactions in animals and staff, and with increased adhesion to the tissues of the animal, which ensures the prolonged action of the drug in high quality during the course of complex therapy treatment and low costs for manufacture and use of tools.

The problem is solved by the fact that an intrauterine device and a method for the prevention of endometritis in cows have been proposed and clinically tested in laboratory and industrial conditions, using an antimicrobial agent containing a supercritical CO ₂ -extract of calendula for the implementation of the method in a complex therapy, and a water-soluble substance being used as the active base organosilicon derivative of glycerol with transmucosal activity, the composition of which corresponds to the formula, (CH ₃ ) ₂ Si (C ₃ H ₇ O ₃ ) ₂ × C ₃ H ₈ O ₃ , when the ratio of components in the tool, wt.%:

supercritical CO ₂ marigold extract  - 0.5; water soluble organosilicon glycerol derivative compound  - up to 100.

According to the proposed method, intrauterine administration of the drug is carried out 3-5 times, with an interval of 48 hours, at the rate of 100-200 g per injection using a Janet syringe and a polystyrene pipette for artificial insemination, while the drug is diluted with sterile distilled water before administration in a ratio of 1: 2.

The ratio of the components of the agent was selected empirically on the basis of an analytical review and the production experience of the authors, as contributing to the production of a stable, non-delaminating composition, convenient for intrauterine administration with a sufficient shelf life and practically proven high therapeutic effect.

The main component of the product is the CO ₂ -extraction of calendula is an oily pasty mass from orange to brown. It tastes bitter with a strong odor characteristic of calendula flowers. Soluble in alcohols and oils, insoluble in water.

Calendula CO ₂ extract obtained under supercritical parameters of carbon dioxide has a wide range of pharmacological activity, preserving all the properties of a living plant: it has antiseptic, anti-inflammatory, wound healing effects. Significantly expressed its bactericidal properties against a number of pathogens, especially staphylococci and streptococci.

Calendula extract is a creamy oily mass with a strong odor characteristic of the feedstock, an environmentally friendly product that is not microbiologically seeded unlike dry materials, is not contaminated with microflora, does not contain pesticides and herbicides, and supercritical CO is used as the active substance _2- calendula extract produced by LLC "Grumant" of the Novgorod region.

In the proposed tool as a hydrophilic base use a water-soluble organosilicon derivative of glycerol, the composition of which corresponds to the formula (CH ₃ ) ₂ Si (C ₃ H ₇ O ₃ ) ₂ × C ₃ H ₈ O ₃ , which has a set of positive properties: high transmucosal and decongestant activity, favorably affects the processes of epithelization, non-toxic, has optimal viscosity and adhesive properties.

The compound is a clear, colorless, viscous liquid, soluble in water, alcohol, insoluble in chloroform and ether. Obtained by the interaction of dimethyldiethoxysilane with glycerol in a molar ratio of 1.00: 2.65 by heating the reaction mass to 120-130 C, holding at this temperature for at least 4 hours with vigorous stirring, followed by removal of the resulting ethyl alcohol.

The dynamic viscosity of a water-soluble organosilicon derivative of glycerol, (CH ₃ ) ₂ Si (C ₃ H ₇ O ₃ ) ₂ × C ₃ H ₈ O ₃ , is 18.0 Pa · s (20 ± 0.5 ° C), the determination was carried out on Viscotester 6 rotational viscometer. The kinematic viscosity of a 50% solution (composition) is 8.88 centistokes (mm ² / s), was determined on a Ubbelode viscometer with a capillary diameter of 0.86 mm (determination error ± 1%).

The compound was developed at the Institute of Organic Synthesis. I.Ya. Postovsky Ural Branch of the Russian Academy of Sciences (see Shadrina E.V., Khonina T.G., Boyko A.A. et al. Synthesis and study of water-soluble silicon polyolates of their hydrogels based on them. Proceedings of the XI Youth Conference in organic chemistry. Ekaterinburg, 2008 - S.221-224).

A water-soluble organosilicon compound derived from glycerol, (CH ₃ ) ₂ Si (C ₃ H ₇ O ₃ ) ₂ × C ₃ H ₈ O ₃ , additionally has a positive effect on the morphofunctional state of the affected tissues, contributing to reparative processes and improving tissue trophism.

The proposed intrauterine device has an antimicrobial effect and a high ability to stimulate the regeneration of affected and damaged tissues during the implementation of the proposed method of treatment.

The effectiveness of the proposed tool is due to the presence in its composition of active components of a wide spectrum of action: a CO ₂ extract of calendula and a biologically active base - a water-soluble organosilicon derivative of glycerol, the composition of which corresponds to the formula (CH ₃ ) ₂ Si (C ₃ H ₇ O ₃ ) ₂ × C ₃ H ₈ O ₃ .

Used in the proposed method, the tool includes, as active substances, a CO ₂ extract of calendula, which is a commercial preparation.

The preparation of the proposed tool is carried out by mechanical mixing of the components.

After conducting numerous laboratory experiments and animal studies, temporary regulations and instructions for conducting production tests were developed and approved.

The implementation of the method with the proposed tool based on a water-soluble organosilicon compound - a derivative of glycerol, the composition of which corresponds to the formula (CH ₃ ) ₂ Si (C ₃ H ₇ O ₃ ) ₂ × C ₃ H ₈ O ₃ , in the form of a convenient form for intrauterine use, provides prolonged action of the active drug components that make up the drug, along with the positive effect of the essential element of silicon, which is part of the drug and contributes to the improvement of reparative processes in the uterine tissues. Moreover, the transmucosal activity of the base allows not only to use small concentrations of active components in the medium, but also leads to their deeper penetration into the affected uterine tissue, accelerating healing. All this in general increases the effectiveness of the drug and accelerates the healing process when implementing the method of prevention and treatment, showing the non-obvious effectiveness of the proposed method.

The studies conducted by the authors showed good compatibility of the active component and the base - a water-soluble organosilicon derivative of glycerol, the composition of which corresponds to the formula (CH ₃ ) ₂ Si (C ₃ H ₇ O ₃ ) ₂ × C ₃ H ₈ O ₃ , and allowed us to identify their limits quantitative content in the environment, providing the manifestation of the maximum therapeutic effect.

The composition of the product used in the production experiment has the following ratio of components, wt.%: Supercritical CO ₂ -extraction of calendula - 0.5; water-soluble organosilicon derivative of glycerol - up to 100.

Production experience was performed in 2010-2011 at the dairy complex of Shilovskoye LLC, Berezovsky City District, Sverdlovsk Region. The dairy complex contains 670 cows of the Ural black-motley breed, with a milk productivity of 7880 kg of milk per year

For the experiment, two groups of analogous cows were selected with a retention of fetal membranes of 16 animals each, in which afterbirth a retention of the placenta was observed. After surgical separation of the placenta, the animals underwent complex treatment.

As a local antimicrobial therapy in the experimental group, a composition containing a CO ₂ -extract of calendula and a water-soluble organosilicon derivative of glycerol was used. The composition was administered intrauterine, in a dose of 100 ml (before use it was diluted with sterile water in a ratio of 1: 2), from 3 to 5 times (before recovery), with an interval of 48 hours. The control animals were intrauterine administered the antimicrobial drug Ginobiotic, according to the manual. In addition, PDE (denatured emulsified placenta) was administered subcutaneously to cows of both groups at a dose of 30 ml, twice, with an interval of 48 hours.

On the 7th, 14th, 21st day of the experiment, the cows of the experimental group took samples of the uterus for bacteriological studies in the Sverdlovsk Regional Veterinary Laboratory. A bacteriological study of pathogenic and conditionally pathogenic microflora was not isolated from the contents of the uterus of cows.

Observation of animals was carried out daily, assessment of the condition of the genital organs was carried out on 7, 14, 21 days after calving using a gynecological study. The criteria for evaluating the effect of the drugs were the nature of the course of the postpartum period of the cows, the timing of the restoration of the sexual cycle, reproductive function indicators, and milk productivity.

In a highly productive herd, one of the performance indicators is milk production, this is most relevant for pathologies that occur in cows in the first half of lactation, since up to 40-45% of the annual milk yield is obtained in the first 100 days after calving (table 1).

Table 1 Cow Productivity Indicator Control group Experienced group Daily productivity of cows in the maternity ward, kg 33.7 33.5 Productivity of cows during insemination, kg 34.5 37,4

The results showed that the cows of the experimental group had daily productivity with insemination an average of 2.9 kg of milk higher than the cows of the control group.

Indicators of postpartum involutional processes of the reproductive organs of cows and the effectiveness of treatment are shown in table 2.

table 2 The effectiveness of the treatment of cows Indicator Control group n = 16 Experimental group n = 16 Duration of treatment, days 8.0 7.8 Recovery after a course of treatment,% 87.5 one hundred Duration of allocation of suckers, days 21.4 ± 0.5 19.2 ± 1.4 Terms of completion of the involution of the genitals, days 28.8 ± 1.1 27.2 ± 0.7

The results obtained indicate that the recovery after treatment in the experimental group was 100%. An additional course was conducted for two cows of the control group with a change in the antimicrobial preparation and an additional prescription of the PDE drug.

The data presented in table 2 show that the cows of the experimental group showed some acceleration in the timing of postpartum involutional processes compared with the control group. So, the duration of isolation of Lochia was shorter by 2.2 days than in control animals. At the same time, it should be noted that in the normal course of the postpartum period, the allocation of Lochia continues up to 14 days. Therefore, in both groups of animals an elongation of the lochial period was observed. So, in the experimental group, the delay of the lochial process was 5.2 days compared with physiological parameters, and in the control group, by 7.4 days.

The difference in the timing of genital involution in cows was not significant. The criterion for involution was the return of the uterus to the pelvic cavity, the reduction of all parts of the uterus to its original state, and the restoration of normal uterine tone.

The influence of the use of the proposed intrauterine device on the timing of restoration of sexual cyclicity, which in the cows of the experimental group was resumed 7.07 days later relative to the control group, was also noted (table 3).

However, the cows of the experimental group had significantly higher fertility from the first insemination and the insemination index, which undoubtedly indicates the best functional state of the endometrium. The better fertilization of experimental cows in the future naturally led to a decrease in the time of fruitful insemination of animals. The period from childbirth to fertilization in the experimental group was 11.93 shorter than in the control.

Table 3 Cow reproductive performance Indicator Control group n = 16 Experimental group n = 16 The period of restoration of sexual cyclicity after childbirth, days 79.68 ± 6.27 86.75 ± 3.77 Fertility from the 1st insemination,% 37,50,56 62.50 * Insemination index 1.81 ± 0.19 1.32 ± 0.15 * The period from childbirth to fertilization, days 104.62 ± 7.07 92.69 ± 2.80 * * - the difference with the control is significant, P <0.05.

Thus, on the basis of the conducted studies, it is possible to draw a reasonable conclusion that the introduction into the complex schemes of the proposed means of preventive treatment of endometritis with delayed placenta is quite effective.

Positive results using the proposed pharmaceutical agent comprising environmentally friendly, derived from vegetable raw materials CO ₂ extract of calendula, allow to develop new approaches and methods of treatment and prevention of pathologies of obstetric at highly productive cows in industrial production of milk by using modern technology intensive, eliminating the use of antibiotics , which leads to an increase in the yield of marketable milk and additional profit in animal husbandry and can be recommended for widespread use in production.

The economic efficiency of the funds was calculated in accordance with the "Methodology for determining the economic efficiency of veterinary measures."

The data for calculating the cost-effectiveness of using a composition containing a CO ₂ -extract of calendula and a water-soluble organosilicon derivative of glycerol for the prevention of endometritis during retention of the placenta in cows are shown in table 4.

Calculation Formulas:

Y ₀ = Y ₁ + Y ₂ + Y ₃ , where

Y ₀ - total damage;

U ₁ - damage from milk shortage;

In ₂ - damage from under-breeding.

U ₃ - damage from reduced product quality.

Table 4 Data for calculations Indicator Control group Experienced Group Productivity per feed cow per year, kg 7800 7800 The average selling price of 1 centner of milk, rubles, 1300.00 1300.00 Duration of treatment, days 8.0 7.75 Rejection period for commercial milk, days eleven - Productivity during treatment, kg 33.7 33.5 Reduced milk yield on 1 day of infertility, kg 7.8 7.8 Veterinary costs per head, rub. 561.00 611.25 Additional veterinary costs per 1 head, rub. - 50.25 The number of cows, goal. 16 16 The period from birth to fertilization, days 104.62 92.69 The number of days of infertility 74.62 62.69

Y ₁ = 0.1% P · Tb · C, where

Tb - the number of days of infertility (service period - 30 days);

P - productivity per 1 feed cow per year;

C - the purchase price of 1 c of milk;

Y ₂ = 0.003 · Tb · S, where

0,003 - coefficient of under-nutrition of calves for 1 day of infertility;

S-3.61 · C - the cost of the calf.

Y ₃ = Tv · Ps · Ts, where

Tv - the number of days of rejection of milk;

Ps - daily productivity per 1 feed cow during treatment;

C - the purchase price of 1 c of milk;

Pu = U ₀ (control) -U ₀ (experience), where

Pu - damage prevented.

Ev = Pu-Sv, where

Ev - economic effect on 1 head;

Sv - additional costs;

Ev · M - economic effect on a group of animals;

M is the number of animals in the group.

Er = Ev: Sv, where

Er - the economic effect on the ruble of costs.

The calculation results of the prevented damage and economic effect are shown in tables 5-6.

Table 5 Results of calculation of prevented damage, rub. Indicator Control group Experienced group At ₁ 7486.47 6356.79 At ₂ 291.02 235.69 At ₃ 4519.1 - At ₀ 12296.59 6592,48 Poo - 5704.11

Table 6 The results of the calculation of the economic effect, rub. Indicator Experienced group Ev 90461,76 Computer 18099 Er 112.52

The above calculations convincingly show that the use of the developed means for the prevention of endometritis during retention of the placenta in cows is economically feasible. The economic effect per ruble of costs calculated on prevented damage due to the reduction of infertility days is 112.52 rubles per head.

As can be seen from the presented research results, the application of the proposed method for the prevention of postpartum endometritis in cows with retention of the placenta using an intrauterine device based on a water-soluble organosilicon derivative of glycerol positively affects the reproductive function, while the main indicator of reproduction regularity is significantly reduced - the period from childbirth to fertilization and increased output.

Claims (3)

1. An agent for the prevention of endometritis in cows, including antimicrobial active ingredients and a base, characterized in that the supercritical CO ₂ -extract of calendula is included as antimicrobial active ingredients, and the base is silicon glycerolate - organosilicon glycerohydrogel - a water-soluble organosilicon derivative of glycerol with transmucosa activity , the composition of which corresponds to the formula (CH ₃ ) ₂ Si (C ₃ H ₇ O ₃ ) ₂ · C ₃ H ₈ O ₃ in the ratio, wt.%:
supercritical CO ₂ marigold extract 0.5 organosilicon glycerohydrogel up to 100 2. The means for the prevention of endometritis in cows according to claim 1, characterized in that the agent uses supercritical CO ₂ as an active substance - calendula extract produced by OOO Grumapt, Novgorod Region. 3. A method for the prevention of endometritis in cows, including complex therapy with intrauterine administration of antimicrobial agents, characterized in that during treatment, the agent according to claim 1 with increased penetrating effect is administered to the cows, and the agent is administered intrauterine 3-5 times, with an interval of 48 h, at the rate of 100-200 g per administration, while the product is diluted with sterile distilled water before use in a ratio of 1: 2.