RU2672250C1 - Means for treatment and prevention of acute postpartum endometritis of farm animals - Google Patents

Abstract

FIELD: veterinary science.SUBSTANCE: invention relates to veterinary medicine, in particular to an agent for treatment and prevention of acute postpartum endometritis of farm animals. Product contains active substances and foaming base, including sodium bicarbonate, citric acid, sodium sulfate, calcium stearate, potato starch, as active substances ceftriaxone, carbacholine, yarrow extract in powder and aloe extract in the following ratio, wt. %: ceftriaxone – 1.0; carbacholine – 0.05; extract of yarrow (powder) – 10.0; aloe extract – 8.0; sodium bicarbonate – 38.95; citric acid – 32.0; sodium sulfate – 2.0; calcium stearate – 2.0; potato starch – 16.0.EFFECT: invention allows to increase therapeutic efficacy, combines an antibacterial effect on conditionally pathogenic microflora in the uterus, anti-inflammatory effect, contractile and regenerating effects on the myometrium and uterine mucosa.1 cl, 2 tbl, 3 ex

Description

The invention relates to veterinary medicine, in particular to obstetrics and gynecology, and is intended for the treatment and prevention of acute postpartum endometritis of farm animals.

There is a method of treating postpartum endometritis (Chervyakov D.K., Evdokimov P.D., Vishker A.S. Medicines in veterinary medicine. Handbook. Edition. 2, revised and additional M: Kolos. - 1977. - 415 s .), involving intravenous infusion of 40% glucose solution, 10% calcium chloride solution, intramuscular injection of 4% gentamicin, trivitamin, 2% sinestrol, subcutaneous injection of 40 units of oxytocin, 0.1% carbacholine and additional autohemotherapy according to the scheme 60, 80, 100 120, suppositories based on furazolidone, massage of the uterus and lavage of the cavity with 4% ichthyol solution. Duration of treatment - within a month.

The disadvantages of the method are a long and expensive treatment that does not give a 100% positive effect, in which a transient acute inflammatory process is possible in a chronic form, which leads to loss of productivity, and sometimes to infertility, and, accordingly, to significant economic losses.

The study revealed an analogue - foaming suppositories "Iodopen" (Iodopen) - a drug (antiseptic), contains 1.5 g of iodine-povidone (1.57% active iodine) (Vidal Handbook "Medicines for veterinary use in Russia" M .: Vidal . - 2011. - 532 s .; RU No. 2155046, 2000), actively used in obstetrics and gynecology. As the active substance "Iodopen", the imported pharmaceutical substance "Iodpovidone 30/06" is used, which for the manufacture of suppositories is purchased in Germany from the well-known pharmaceutical company "BASFCorporation" (PVP - iodine (iodopovidone). Technical information of the company "BASF", 1997. - 21 s.).

The closest analogue is (patent RU 2617538, A61K31 / 00, publ. 04.25.2017) a tool for the treatment and prevention of postpartum endometritis of farm animals and contains sodium bicarbonate, citric acid, sodium sulfate, calcium stearate, potato starch, ceftriaxone, carbacholine and aloe extract in the following ratio of components, wt. %: ceftriaxone - 1.0; carbacholine - 0.05; aloe extract - 8.0; sodium bicarbonate - 38.95; citric acid - 32.0; sodium sulfate - 2.0; calcium stearate - 2.0; potato starch - 16.0.

However, this remedy has disadvantages: the lack of local and general anti-inflammatory effect, a long therapeutic course, which involves the use of additional drugs, the content of high doses of iodine, having side effects, and also high cost.

The objective of the claimed technical solution is to develop a drug for the treatment and prevention of postpartum endometritis of farm animals on a foam-forming basis, acting on all parts of the pathological process, combining antibacterial, anti-inflammatory, contractile and restorative effects, with high therapeutic efficacy.

The problem is solved by applying yarrow extract.

The essence of the invention lies in the fact that the tool for the treatment and prevention of acute postpartum endometritis of farm animals, containing active substances and a foaming base, including ceftriaxone, carbacholine, aloe extract, sodium bicarbonate, citric acid, sodium sulfate, calcium stearate, potato starch, while , as active substances use yarrow extract in the form of a powder in the following ratio of components, wt.%:

ceftriaxone - 1.0;

carbacholine - 0.05;

yarrow extract (powder) - 10.0

aloe extract - 8.0;

sodium bicarbonate - 34.95;

citric acid - 30.0;

sodium sulfate - 2.0;

calcium stearate - 2.0;

potato starch - 12.0.

Effect: the components of the drug provide anti-inflammatory and antimicrobial (bactericidal), anti-allergic, wound healing and antispasmodic effects.

Component Feature

Ceftriaxone is a semi-synthetic antibiotic belonging to the 3rd generation cephalosporins group. The drug is effective against many gram-positive and has a high activity against gram-negative bacteria. It affects bactericidal strains of bacteria resistant to penicillin, aminoglycosides, sulfonamides. The mechanism of the antimicrobial action of the drug is associated with inhibition of the activity of the transpeptidase enzyme by peptidoglycan blockade, a violation of the formation of mucopeptide of the cell wall of microorganisms. It can act on multi-resistant strains that are resistant to penicillinase, first-generation cephalosporins, aminoglycosides. The drug is less active against gram-negative cocci than cephalosporins of the first and second generations.

Carbacholine is a white crystalline powder with a weak specific odor, hygroscopic, readily soluble in water (1: 1), the pH of the solution is 5.0-7.0, more difficult in alcohol, practically insoluble in ether and chloroform. The solutions are sterilized at a temperature of 100 ° C for 30 minutes. The drug is incompatible with alkalis, heavy metals, carbonates, tannins. In terms of chemical structure and pharmacological properties, carbacholine is close to cholinergic substances (acetylcholine). Its action occurs 5-10 minutes after administration and lasts for several hours.

Carbacholine increases tone and strengthens the contractions of the muscles of the uterus, stomach and intestines, digestive, bronchial, sweat, salivary and lacrimal glands, dilates peripheral vessels, slows the heart rate, narrows the pupil, and reduces intraocular pressure.

Yarrow extract is a herbal remedy, the essential oil, tannins and chamazulene included in it provide anti-inflammatory and antimicrobial (bactericidal), anti-allergic, wound healing and antispasmodic (smooth muscle) effects. Hemostatic effect due to fibrinogen activation, does not lead to blood clots

Aloe extract is a herbal remedy. Aloe juice has a bitter taste and has many vitamins and enzymes that have anti-inflammatory effects and improves the regeneration of the skin and mucous membranes. Emodin is a substance that is part of this natural medicine that can inhibit the growth of certain pathogenic bacteria and inactivate a number of viruses.

Aloe extract contains biogenic stimulants that, when ingested, stimulate cell metabolism, regeneration and trophism, as well as increase protective functions.

The composition is presented in the form of a dosage form (suppository) containing active substances - cefotaxime, carbacholine, yarrow extract, aloe extract and a foaming base (pharmaceutical blowing agents and former), including sodium bicarbonate, citric acid, sodium sulfate, calcium stearate, potato starch.

Get the claimed tool as follows. Potato starch and citric acid are weighed and mixed, then the required amount of carbacholine is added and mixed. Separately, cefriaxone, yarrow extract (in powder), calcium stearate, sodium bicarbonate and sodium sulfate are weighed and mixed. Then both the resulting masses are mixed with each other and crushed to a pulverized state in an electric mill. The resulting mass is irrigated with a measured amount of aloe extract and dried in a thermostat at 30–55 ° C to a residual moisture content of not more than 10%, subject to drying conditions for thermally unstable materials.

Then, the cavity of the press is filled with the obtained suppository mass, using the piston, the mass is fed into the matrix, which is a suppository shape, or punches of the corresponding shape. Pressing is carried out according to the instructions for the pressing device. The duty cycle lasts 45 seconds.

The proposed tool is a solid sticks 65 mm long, 16 mm in diameter, 12 g in weight, cylindrical in shape, with rounded ends, white, odorless.

Before the introduction of the claimed funds carry out the toilet of the external genitalia and the root of the tail. Suppositories are injected into the uterine cavity, hand clad in a disposable plastic glove. The drug is administered intrauterine one suppository: for treatment - with an interval of 24 hours before recovery, for prevention - with an interval of 24 hours for 5 days from the date of birth.

The resulting suppository in contact with the mother liquor (exudate) forms a foam, due to the reaction of neutralization of sodium bicarbonate with citric acid, filling the uterine cavity, providing contact of the drug with the inflamed tissue.

The claimed tool, in the treatment of farm animals with a diagnosis of postpartum endometritis, has a pronounced therapeutic effect, which is achieved by the presence in the complex preparation of yarrow extract. Yarrow extract enhances the antimicrobial properties of Ceftriaxone due to the bactericidal and bacteriostatic properties of mihamazulene, which is a component of yarrow extract, on the conditionally pathogenic uterine microflora. Chamazulen also enhances the action of carbacholine, acting on the myometrium, causing smooth muscle contractions, which contributes to the even distribution of the claimed drug throughout the uterine cavity, in addition, chamazulen acting on the carbacholine chains, strengthens their connection, as a result, the properties of carbacholine to reduce the smooth muscle of the uterus are prolonged.

The action of aloe vera extract on the regeneration of the mucous membrane is enhanced by tannins, which are part of the yarrow extract, due to this interconnection, the recovery process of the uterine mucosa is accelerated, and the local anti-inflammatory effect is manifested within 10 minutes after application of the claimed agent.

Example 1

Calculation of the optimal composition of the product.

The ratio of active components in the proposed tool was determined taking into account the instructions for their use in three compositions with a ratio of components, mass. %:

Composition 1. Ceftriaxone - 1.60; carbacholine - 0.11; yarrow extract - 10.00; aloe extract - 8.49; sodium bicarbonate - 32.00; citric acid - 32.00; sodium sulfate - 2.50; calcium stearate - 2.50; potato starch - 10.00.

Composition 2. Ceftriaxone - 1.00; carbacholine - 0.05; yarrow extract - 10.00; aloe extract - 8.00; sodium bicarbonate - 34.95; citric acid - 30.00; sodium sulfate - 2.00; calcium stearate - 2.00; potato starch - 12.00.

Composition 3. Ceftriaxone - 0.50; carbacholine - 0.01; yarrow extract - 11.50; aloe extract - 7.50; sodium bicarbonate - 33.50; citric acid - 33.50; sodium sulfate - 2.50; calcium stearate - 2.50; potato starch - 8.00.

To determine the optimal ratio of components in the proposed tool, cows were selected at the age of 3-4 years from the Swiss breed, with signs of acute postpartum purulent-catarrhal endometritis. Of these, according to the principle of pairs of analogues, 3 groups were formed, 6 goals each. The cows of the first group were administered the drug as part 1, the second as part 2, the third as part 3, intrauterine, one suppository with an interval of 24 hours until recovery.

The experimental results are presented in table 1.

Table 1. Analysis of the results of various formulations for the treatment and prevention of postpartum endometritis.

Indicators Group I II III Quantity, goal. 6 6 6 The onset of improvement, days. 3.22 ± 0.21 3.01 ± 0.12 4.10 ± 0.35 Therapeutic course, days 5.05 ± 0.15 4.09 ± 0.15 7.23 ± 0.63 Recover, goal. 6 6 6

Improvement was noted in animals of the first and second groups on the third day, in cows of the third group, improvement occurred on 4-5 days. Experimental animals showed a decrease in inflammatory edema, the amount of catarrhal-purulent exudate, the volume of the uterus, and fluctuations. Recovery occurred in cows of group II on average 1 day after the start of treatment earlier than cows of group I, and cows of group III — 3 days later, relative to cows of group II. Thus, the use of the claimed funds in composition 2 for the treatment of cows with signs of acute postpartum purulent-catarrhal endometritis contributes to their rapid recovery.

Example 2

To determine the therapeutic effectiveness of the proposed tool in the FPZ “Pridonsky” in the Oktyabrsky district of the Rostov Region, 10 cows of red steppe breed were selected at the age of 3-5 years.

In the FPZ “Pridonsky” of the Oktyabrsky District, Rostov Region, animals are kept in tethered keeping, and are released to bases in the daytime. The economy is considered safe for infectious diseases.

For the study of animals with signs of acute postpartum purulent-catarrhal endometritis according to the principle of pairs of analogues, 5 animals were divided into 2 groups of 5 goals. Suppositories were administered intrauterine, one suppository at an interval of 24 hours until recovery. Cows were considered to have recovered upon cessation of vaginal discharge.

On days 5–6, the cows of the first group had their outflows reduced, and ended on day 16 after the start of the experiment. In cows of the second group, significant improvements came already on 3-4 days, and full recovery on 7-10 days.

Thus, the new drug showed a clear superiority in therapeutic efficacy (2 times) in the treatment of acute purulent-catarrhal endometritis in cows in comparison with No. 2617538.

Example 3

The bactericidal properties of the claimed agent for the treatment and prevention of postpartum endometritis were determined by serial dilution in a liquid nutrient medium and diffusion in agar.

When determining the bactericidal activity in a liquid nutrient medium, its fractional (multiple) dilutions in BCH were made. Daily test microorganisms isolated from cows with acute postpartum endometritis (Streptococcus, Staphylococcus, Escherichia, Proteus) were used as test cultures.

Test cultures were added to the broth containing the preparation in a decreasing concentration (dilution 1: 128). The microbial load was 1 billion microbial bodies in 1 ml tubes with nutrient medium were incubated for 18-20 hours at a temperature of 37 ° C. The activity of the drug was determined by inhibiting the growth rate and death of microorganisms.

The claimed drug showed a pronounced bactericidal and bacteriostatic effect in relation to all tested cultures of microorganisms. At a dilution of 1:16 in relation to the culture of Str.epidermis and E. Coli, at a dilution of 1:32 in relation to the culture of St. Aureus and Pr. vulgaris.

In three Petri dishes on MPA, a culture of microorganisms was isolated from the uterine exudate of cows with signs of acute postpartum purulent-catarrhal endometritis. Wells with a diameter of 5 mm were formed in MPA and 0.25 ml of the drug were added to them. After a 24-hour incubation in a thermostat at a temperature of 37 - 38 ° C, the diameters of the zones of growth inhibition of microbial colonies were determined.

The results of a study of the bactericidal effect of the new drug on MPA are presented in table 2.

Table 2. The bactericidal effect of the claimed drug.

A drug Test culture Zone of growth inhibition, mm Claimed new remedy Str.epidermis 23.17 ± 0.45 St. aureus 22.78 ± 0.37 E. coli 21.15 ± 0.23 Pr. vulgaris 24.18 ± 0.12

It was revealed that all tested cultures of microorganisms showed sufficient (z.s. 21.15 - 24.18 mm) sensitivity to all the microorganism cultures due to exposure to the main antimicrobial complex of the claimed drug Ceftriaxone - Yarrow Extract. This complex exceeds on average 3.81 ± 0.26 mm in the zone of growth retardation, relative to statistical and laboratory data, when using the mono component "Ceftriaxone".

Claims (10)

An agent for the treatment and prevention of acute postpartum endometritis of farm animals, containing active substances and a foaming base, including ceftriaxone, carbacholine, aloe extract, sodium bicarbonate, citric acid, sodium sulfate, calcium stearate, potato starch, characterized in that it is used as an active substance yarrow extract in the form of a powder in the following ratio of components, wt.%: ceftriaxone - 1.0; carbacholine - 0.05; yarrow extract (powder) - 10.0 aloe extract - 8.0; sodium bicarbonate - 34.95; citric acid - 30.0; sodium sulfate - 2.0; calcium stearate - 2.0; potato starch - 12.0.