RU2624868C2 - Preparation method of the complex gel for mastitis treatment and prevention in cows and complex gel on its basis - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: complex gel contains antimicrobial and anti-inflammatory drugs. As the antimicrobial drugs it contains metronidazole, chlorhexidine bigluconate 0.05%, tea fungus culture biomass. As the anti-inflammatory drugs it contains the plant components extracts: mother coltsfoot, chamomile pharmacy, birch buds, celandine, nettle, horseradish and chlorophytum, wherein the propylene glycol is used in the ratio of 1:5 as the extracting agent, additionally include the acrylic acid and triethanolamine in the following ratio, g/l: chlorhexidine digluconate 0.05% 9-13, metronidazole 3.5-5.0, acrylic acid 2.5-3.5, triethanolamine 1.0-1.5, mother coltsfoot extract 1.0-1.5, chlorophytum extract 1.0-1.5, chamomile pharmacy 1.0-1.5, birch buds extract 1.0-1.5, celandine extract 1.0-1.5, nettle extract 1.0-1.5, horseradish extract 1.0-1.5, tea fungus culture biomass - the rest. The claimed method of the complex gel preparation for the treatment and prevention of mastitis in cows concludes in mixing of antimicrobial and anti-inflammatory drugs, homogenization. The plant components are pre-dried, then in the amount of 1-1.5 g each it is homogenized and poured with the extractant. Propylene glycol is used as the extractant in the ratio of 1:5. It is additionally infused for 14-15 days and filtered. Prepare the tea fungus culture biomass, then infused for 10-12 days, then homogenize with the zoogloea of the tea fungus, dilute it with the infusion of tea fungus in the ratio of 1.6:1, respectively, until the homogeneous gel mass is obtained. Digest for 10-12 minutes, with further step by step addition of all components into the mixer, homogenization until the homogeneous gel mass is obtained and packed into the sterile syringes.

EFFECT: claimed group of inventions application is highly effective for the mastitis treatment and prevention in cows.

2 cl, 5 tbl, 9 ex

Description

FIELD OF THE INVENTION

The invention relates to veterinary medicine, in particular to a method for preparing a complex gel-like preparation for the treatment and prevention of mastitis in cows and a complex gel-like preparation based on it, and can be used in obstetrics and gynecology when creating drugs based on plant extracts and antibacterial components, and for prophylaxis in the complex treatment of endometritis of sheep and pigs.

State of the art

It is known a means for treating animals with postpartum endometritis, including antimicrobial and anti-inflammatory drugs and a polymer base, while it contains ethacridine lactate and cefatoxime as an anti-microbial drug, and soy aloe as an anti-inflammatory drug in the following ratio of components, mass. %: ethacridine lactate 0.6; aloe juice 50.4; cefatoxime 2, urea 15.0; formalin neutral 10; distilled water 5; glycerol 17.0 (see Pat. RU No. 2367416, IPC A61K 31/047, A61K 1/115, A61K 31/17, A61K 31/473, A61K 36/886, A61P 15/00, published on 09/20/2009 )

The disadvantage of this tool is that it does not have an antihistamine effect, namely it does not relieve spasm of smooth muscles, does not reduce capillary permeability, since the inflammatory process causes increased sensitivity to tissue decay products and microbial cell antigens.

A known drug for the treatment of mastitis in cows, containing a plant base and ammonia, while it additionally contains dimexide, and as a plant base fuz obtained in the manufacture of oil from pumpkin seeds, and a carrier type Aerosil-380 in the following ratio of starting components to mass . %:

- 30% solution of dimexide - 4-5;

- 0.5% ammonia solution (ammonia) - 2-4;

- carrier Aerosil-380 - 2-5;

- fuz - the rest (see Pat. RU No. 2170085, IPC A61K 31/00, A61K 35/78, A61P 15/00 publ. 07/10/2001).

The disadvantage of this drug is its low antibiotic activity, and, consequently, the low effectiveness of the treatment of mastitis.

Known drug for the treatment and prevention of mastitis in cows, containing antimicrobial, anti-inflammatory drugs and distilled water, while it additionally contains licorice root, and as an antimicrobial drug contains metronidazole, and as an anti-inflammatory drug - ciproflosacin, in the following ratio of components, g / l:

- licorice root 80-85 g;

- metronidazole 3.5-4.0 g;

- ciprofloxacin 2.0-2.5 g:

- distilled water - the rest (see US Pat. RU No. 2537143, IPC A61K 36/484, A61K 31/415, A61K 31/395, A61P 15/00, A61P 29/00, A61P 31/04 publ. 12/27/2014 .).

The disadvantage of this drug is the low antibiotic activity and the effectiveness of the treatment of mastitis in cows.

The closest in technical essence and the achieved positive effect and adopted by the authors for the prototype is a method of preparing a drug for the treatment and prevention of mastitis in cows and a drug based on it, including mixing antimicrobial and anti-inflammatory drugs, homogenization, and it contains metronidazole, chlorhexidine as antimicrobial drugs digluconate 0.05%, biomass of Kombucha culture, and as anti-inflammatory drugs - extracts of plant components: ma b-stepmother, pharmacy chamomile, birch buds, large celandine, nettle and horseradish (see Gandraburova N.I., Timchenko L.D., Rzhepakovsky I.V., "Principles of modeling the new veterinary drug" UTEROMASTIN ", SKFU , Stavropol, pp. 69-73).

The disadvantage of this drug is that it does not have a sufficiently high anti-inflammatory effect in relation to microorganisms and on the morphofunctional state of the uterine mucosa.

Disclosure of invention

The objective of the invention is to develop a method for the preparation of a complex gel-like preparation for the treatment and prevention of mastitis in cows and a complex gel-like preparation based on it, having a pronounced antimicrobial and anti-inflammatory broad spectrum action with simultaneous, analgesic, regenerating, biostimulating, antiprotozoal and antibacterial action, namely the suppression of most of the main and concomitant pathogenic microorganisms, the excitation of immune mechanisms protection, as well as a simpler and cheaper method of preparation based on Kombucha, plant extracts and antibacterial components.

The technical result that can be obtained using the present invention is reduced to a broad spectrum antimicrobial and anti-inflammatory action with simultaneous analgesic, regenerative, biostimulating, antiprotozoal and antibacterial effects, stimulation of immune defense mechanisms, simplification and cheapening of the method of preparation based on tea mushroom, extracts plants and antibacterial components.

The technical result is achieved using a complex gel-like preparation for the treatment and prevention of mastitis in cows containing antimicrobial and anti-inflammatory drugs, moreover, it contains metronidazole, chlorhexidine bigluconate 0.05%, biomass of Kombucha culture, and as anti-inflammatory drugs - extracts of plant components: coltsfoot, chamomile, birch buds, celandine, nettle, horseradish and chlorophytum, where as an extractant Propylene glycol is used in a ratio of 1: 5, further comprising acrylic acid and triethanolamine in the following ratio in g / l:

- chlorhexidine bigluconate 0.05% 9-13 - metronidazole 3,5-5,0 - acrylic acid 2.5-3.5 - triethanolamine 1.0-1.5 - coltsfoot extract 1.0-1.5 - chlorophytum extract 1.0-1.5 - pharmacy chamomile extract 1.0-1.5 - birch bud extract 1.0-1.5 - large celandine extract 1.0-1.5 - nettle extract 1.0-1.5 - horseradish extract 1.0-1.5 - Kombucha biomass culture rest

The technical result is achieved using the method of preparing a complex gel-like preparation for the treatment and prevention of mastitis in cows, which consists in mixing antimicrobial and anti-inflammatory drugs, homogenization, and it contains metronidazole, chlorhexidine bigluconate 0.05%, Kombucha culture biomass as antimicrobial agents , and as anti-inflammatory drugs - Extracts of plant components: coltsfoot, pharmacy chamomile, birch buds, large celandine, nettles, horseradish and chlorophytum, and additionally acrylic acid and triethanolamine, moreover, the plant components are pre-dried, then each is homogenized in an amount of 1-1.5 g, poured with an extractant, which is used propylene glycol, in a ratio of 1: 5 is additionally infused for 14 -15 days and filtered, the biomass of Kombucha culture is prepared, infused for 10-12 days, then homogenized with zoogloss of Kombucha, diluted with infusion of Kombucha in a ratio of 1.6: 1, respectively, to obtain a uniform gel mass, autoclave for 10-12 minutes, followed by a phased addition of all components to the mixer, homogenization to obtain a homogeneous gel-like mass and packaging in sterile syringes.

Thus, the technical result is achieved due to the action of antimicrobial and anti-inflammatory properties of the ratio of the components used in the invention:

- chlorhexidine bigluconate 0.05% is used as a therapeutic and prophylactic agent for various infections, for antiseptic treatment and disinfection, which exhibits bacteriostatic or bactericidal action against gram-positive and gram-negative bacteria. Bacteriostatic effect is manifested in a concentration of 0.01% or less; bactericidal - in a concentration of more than 0.01% at a temperature of 22 ° C and exposure for 1 min. Fungicidal action - at a concentration of 0.05%, a temperature of 22 ° C and exposure for 10 minutes. Virucidal effect (against ligufilnyh viruses) - manifests itself at a concentration of 0.01-1%. It acts on bacterial spores only at elevated temperatures. Effective against gram-positive and gram-negative bacteria - Treponema spp., Neisseria gonorrhoeae, Trichomonas spp., Chlamydia spp., Ureaplasma spp .;

- metronidazole (metrogil) - an antiprotozoal and antibacterial agent with a wide spectrum of action. The mechanism of action of the drug is to restore the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group of metronidazole interacts with the DNA of the cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria. The active substance of the drug is metronidazole. Indications: protozoal infections (amoebiasis, trichomoniasis, giardiasis, balantidiasis, trichomonas vaginitis and urethritis, amoebic dysentery); anaerobic infections (caused by Bac. fragilis and other bacteroids, fusobacteria, eubacteria, clostridia, anaerobic cocci);

- acrylic acid is a copolymer of acrylonitrogen Acrylic acid / acrylonitrogens copolymer, taking into account its binding properties and viscosity control, use it as a primary emulsifier;

- triethanolamine chemical pH regulator, aromatic ingredient, surfactant emulsifier, neutralizes fatty acids, promotes better dissolution of oils and other ingredients that are not completely soluble in water, promotes the mixing of water-soluble and fat-soluble components;

- coltsfoot extract of ordinary (Tussilago farfam L.) - has an anti-inflammatory effect, enhances the secretion of bronchial glands, softens, antiseptic, expectorant, antispasmodic and diaphoretic effect, tussilagin glycoside, sitosterol, malic acid, gallic and carotenoids, tannins, mucus, dextrin, inulin, flavonoids, vitamin C, traces of essential oil, inflorescences contain phytosterol, triterpene alcohols, arnidol and firadiol, carbohydrates, carotenoid taraxanthin, stigmasterol, sitoste in, rutin, geptakozan, tannins;

- the extract of chlorophytum crested (Chlorophitum comosum), contains a wide range of amino acids in high concentrations: cystine, leucine, valine, phenylalanine, histidine, which have a powerful antioxidant, detoxification, reparative, immunomodulating effect, are involved in metabolic cellular and tissue processes, activates biochemical reactions, helps to reduce pain during inflammation;

- extract of chamomile pharmacy, medicinal (Matricaria chamomilla), has antispasmodic, anti-inflammatory, antiseptic, sedative and some analgesic, choleretic effect, reduces fermentation processes. The mechanism of antispasmodic action is explained by the cholinolytic properties of plant glycosides. Chamomile preparations accelerate the processes of epithelial regeneration in experimental ulcers and delay the development of experimental inflammation. Chamomile pharmacy contains nicotinic, salicylic, ascorbic acids, phytosterol, bitterness, gum, choline, essential oil (containing more than 40 components, such as bisabolol and its oxides, chamazulene and others), tannins, dioxicoumarin, fats, wax, sugar, glycoside umbelliferone, glycerides of fatty acids, pectins, mucus. It is to them that she owes her useful and healing properties. Pharmacy chamomile flowers contain up to 1.8% (usually 0.3-1.0%) of essential oil, chamazulene (up to 10% in breeding varieties), as well as flavonoids, derivatives of apigenin, luteolin and quercetin, which are considered also have anti-inflammatory and antiviral effects, beta-carotene, coumarins, sitosterol, carotene, antispasmodic glycoside, diaphoretic action glycoside, polysaccharides and organic acids. The remaining components also have a therapeutic effect: fernesene (promotes epithelization and granulation of tissues), bisaboloxide A (has anti-inflammatory and antispasmodic effects), herniarine and N-indicycloester (both antispasmodic). Inflorescences of chamomile pharmacy accumulate macronutrients (mg / g): 41.80; Ca - 8.30; Mg - 3.10; Fe - 0.30; Mn 0.29; Cu - 0.78; Zn 0.80; Co - 0.16; Cr 0.09; Al 0.27; Ba - 0.20; V - 0; 08; Se - 7.20; Ni 0.24; Pb - 0.07; I - 0.07;

- extract of birch buds (Betula alba), has anti-inflammatory, diuretic, wound healing, diaphoretic, antibacterial effects. They contain essential oil, flavonoids, vitamin PP, saponins, and the composition of the essential oil (3.5-5.3%) includes betulene, betulol, betulenic acid and naphthalene, and the leaves contain tannins, ascorbic acid, flavonoids , saponins, essential oil, betuloretin acid, in addition, they contain a lot of volatile. The leaves also contain: ash - 5.22%; macronutrients (mg / g): potassium - 11.40, calcium - 12.50, magnesium - 3.80, iron - 0.30; trace elements (μg / g): - manganese - 374.00, copper - 7.52, zinc - 159.00, cobalt - 0.16, molybdenum - 1.44, chromium - 0.56, aluminum - 98.32, barium - 85.76, vanadium - 0.24, selenium - 0.29, nickel - 5.28, strontium - 11.70, lead - 2.64, boron. Concentrates manganese, zinc, barium, especially zinc. Birch bark contains up to 15% tannins, triterpene alcohol betulin, essential oil, glycosides - betuloside and gaulterin, suberin. The birch buds contain: ash - 5.55%; macronutrients (mg / g): potassium - 12.60, calcium - 7.40, magnesium - 2.00, iron - 0.30; trace elements (μg / g): manganese - 127.00, copper - 10.80, zinc - 100.00, cobalt - 0.72, chromium - 0.56, aluminum - 153.80, barium - 35.20, vanadium - 0.48, selenium - 0.70, nickel - 5.84, strontium - 7.52, lead - 1.36, boron - 19.60. Concentrates zinc, selenium;

- large celandine extract (Chelidonium majus) has anti-inflammatory, antipruritic, antimicrobial, wound healing and cauterizing effects, while the main properties of the celandine are antispasmodic, choleretic and anti-inflammatory (bactericidal). The highest pharmacological activity has alkaloids of celandine. For example, chelidonin gives a pronounced analgesic and sedative effect. In addition, this alkaloid has an antispasmodic effect on smooth muscle organs, has hypotensive and bradycardic properties. Homochelidonin, another celandine alkaloid, on the contrary, gives an exciting-convulsive effect and exhibits local anesthetic activity. Alkaloid protopin reduces the reactivity of the autonomic nervous system and enhances the tone of smooth muscles. For cheleritrin, a pronounced local irritant effect is characteristic. Alkaloids were found in all parts of the plant, the amount of which in the grass can reach 0.27-2.25%, and in the roots - up to 4%. In addition to alkaloids, celandine contains flavonoids, saponins, tannins, vitamins A, C, organic acids (1.40-4.32%). Of the organic acids, the most common are chelidonic, citric, malic, ascorbic, and succinic. In addition, the celandine contains the highest aliphatic alcohol - chelidoniol, and the fruit contains up to 40% fatty oil. The alkaloids of the subgroups are contained in the celandine: protoberberin - berberine, koptizin, stylopin (a derivative of tetrahydrotropoberberin); protopin - protopin, allocryptopin; benzophenontridine - chelidonin, cheleritrin, helirubin, sanguirytrin, nitrogen-containing compounds - choline, histamine, tyramine. The alkaloids in the celandine can be both in a free state and in a bound form. They are most often associated with chelidonic acid, which in its structure is very close to meconic acid;

- dioecious nettle extract (Urtica dioica), has a wide range of healing and therapeutic properties: it accelerates the blood coagulation process, increases the content of hemoglobin and red blood cells, improves metabolism, lowers blood sugar, strengthens the immune system, has a general strengthening effect, helps to resist the effects of radiation , increases the tone of the intestines and cardiovascular system, enhances the tone and contraction of the muscles of the uterus, normalizes the menstrual cycle, has a stimulating and tonic effect Stimulate epithelialization of the affected tissues, has the property of restoring the function of smell, regulates the acid-base balance in the body, anti-inflammatory, multivitamins, antipruritic, choleretic, diuretic, hepatoprotective (protecting liver cells), expectorant, an analgesic, antiseptic, anti-convulsive, and other properties. It contains almost all vitamins, many trace elements, organic acids, as well as volatile and tannins, in the seeds - fatty oil. Nettle is rich in biologically active substances, such as glycoside, urticin, flavonoids, phenolic acids. The roots contain up to 2% tannic acids. Nettle leaves contain formic, silicic, pantothenic, oxalic, succinic, lactic, citric and quinic acids. 100 grams of dioica nettle contains 3.7 grams of protein, 0.5 grams of fat, 5.4 grams of carbohydrates, 3.1 grams of fiber, 41 mg of iron, 1.3 mg of copper, 8.2 mg of manganese, 4.3 mg boron, 2.7 mg of titanium, 0.03 mg of nickel. Leaves contain chlorophyll (2-5%), starch (up to 10%), alkaloids (up to 0.29%), ascorbic acid (200 mg /%), carotenoids (up to 50 mg /%);

- horseradish extract (Armoracia rusticana), contains vitamin C, vitamins of group B, PP, ascorbic acid, a large set of essential mustard oils, phytoncides, starch, tarry substances, fiber, a large number of micro and macro elements, has anti-inflammatory and bactericidal qualities, and is also considered a strong natural antibiotic, it contains carbohydrates, fats, nitrogenous substances, many mineral salts (especially potassium - up to 371 mg%), vitamin C (128 mg%), essential oil, the main component of which is allyl chichnoe oil. The sharp taste of horseradish gives the glycoside sinigrin;

- Kombucha culture biomass (extract) - Medusomyces gysevii is a symbiosis of acetic acid bacteria with several types of yeast, which form a cellulose film on the surface of the nutrient medium. Native liquid of Kombucha has a rather complex chemical composition. Mushroom fermentation products contain a large amount of organic acids: acetic, glucuronic, oxalic, citric, malic, lactic, pyruvic, koyevoy, phosphoric and very small amounts of alcohol. Native fluid Medusomyces gisevii also has a wide spectrum of antibacterial action. The antibiotic isolated from the infusion is called bacteriocidin or medusin. In particular, Kombucha exhibits bacteriostatic and bactericidal action against Helicobacter pylori, Salmonella typhimurium, Staphylococcus aureus, Agrobacterium tumefaciens, Bacillus cereus, Shigella sonnei, Salmonella enteritidis, Escherichia coli. Enzyme composition: catalase, lipase, protease, zymase, sucrose, carbohydrase, amylase, tryptic enzymes of kombucha infusion. Lipase promotes the breakdown or formation of fats. Protease promotes the breakdown of protein into amino acids and plays a significant role in the absorption of animal protein. Amylase inhibits the increase in blood sugar by breaking down starch. The presence of trace elements, vitamins (B vitamins, vitamin C, PP, D), tannin and kakhetin helps increase immunity, normalize metabolism. The range of application of Kombucha is very wide. It is used in a number of gastrointestinal diseases (colitis, dysentery, gastritis, dyspepsia), chronic diseases of the gallbladder and liver, tonsillitis and chronic tonsillitis, as a prophylactic for atherosclerosis, polyarthritis, rheumatic heart disease during the decay or mild course of the disease, to increase immunity, infusion of Kombucha and its body is used for burns and infected wounds. Thus, Kombucha has bacteriostatic, fibrinolytic, detoxifying properties, biostimulating, local, moderately irritating effect, stimulates regeneration processes (see Avakyan A.D. Probiotic and prebiotic properties of Kombucha culture fluid // Materials of the Fourth All-Russian Congress on Medical Mycology. - M .: National Acad. Mycology, 2006, p. 214-216).

The essence of the method of preparing a complex gel-like preparation for the treatment and prevention of mastitis in cows and a complex gel-like preparation based on it, is as follows.

Antimicrobial and anti-inflammatory drugs are mixed, homogenized, and it contains metronidazole, chlorhexidine bigluconate 0.05%, biomass of tea mushroom culture as antimicrobial agents, and extracts of plant components: coltsfoot and chamomile as anti-inflammatory drugs pharmacy, birch buds, celandine, nettle and horseradish, while it additionally contains chlorophytum extract, acrylic acid and triethanolamine, and the plant components are preliminarily tub, then in an amount of 1-1.5 g each is homogenized, filled with extractant, where propylene glycol is used as an extractant, insisted in a ratio of 1: 5 for 14-15 days and filtered, at the same time biomass of Kombucha culture is prepared, insisted for 10 -12 days, then homogenized by zoogley of Kombucha, diluted with infusion of Kombucha in a ratio of 1.6: 1, respectively, until a homogeneous gel-like mass is obtained, autoclave for 10-12 minutes, followed by a phased addition of all components to the mixer, homogenize it until a homogeneous gel-like mass is obtained and packed into sterile syringes, while the complex gel-like preparation for the treatment and prevention of mastitis in cows includes antimicrobial and anti-inflammatory drugs, and it contains metronidazole, chlorhexidine bigluconate 0.05%, biomass as antimicrobial agents Kombucha culture, and as anti-inflammatory drugs - extracts of plant components: coltsfoot, pharmacy chamomile, birch buds, large celandine, nettle and horseradish, etc. This further comprising Chlorophytum extract, acrylic acid and triethanolamine in the following ratio in g / l: Chlorhexidine digluconate 0.05% - 9-13; metronidazole - 3.5-5.0; acrylic acid - 2.5-3.5; triethanolamine - 1.0-1.5; coltsfoot extract - 1.0-1.5; chlorophytum extract - 1.0-1.5; chamomile pharmacy extract - 1.0-1.5; birch bud extract - 1.0-1.5; large celandine extract - 1.0-1.5; nettle extract - 1.0-1.5; horseradish extract - 1.0-1.5; homogeneous gel-like mass of Kombucha - the rest.

A brief description of other materials. Table 1 gives a method for preparing a complex gel-like preparation for the treatment and prevention of mastitis in cows and a complex gel-like preparation based on it, the results of studying the organoleptic and toxicological properties of the drug during storage.

In table 2, the same, the study of chronic toxicity of the drug, cumulation coefficient.

In table 3, the same study of the allergenic effect of the drug.

In table 4, the same organoleptic properties of the drug.

In table 5, the same study of the toxicological parameters of the drug.

The implementation of the invention

Examples of specific performance of the method of preparing a complex gel-like preparation for the treatment and prevention of mastitis in cows and a complex gel-like preparation based on it.

Example 1. A method of preparing a complex gel-like preparation for the treatment and prevention of mastitis in cows and a complex gel-like preparation based on it are prepared as follows. Antimicrobial and anti-inflammatory drugs are mixed, homogenized, and it contains metronidazole, chlorhexidine bigluconate 0.05%, biomass of tea mushroom culture as antimicrobial agents, and extracts of plant components such as coltsfoot and pharmaceutical chamomile as anti-inflammatory drugs , birch buds, celandine, nettle and horseradish, while it additionally contains chlorophytum extract, acrylic acid and triethanolamine, and the plant components are pre-dried, for thereby homogenize, fill with an extractant, which is used propylene glycol, in a ratio of 1: 5, insist for 14-15 days and filter, at the same time prepare the biomass of Kombucha culture, insist for 10-12 days, then homogenize the zoogley of Kombucha, dilute it infusion of kombucha in a ratio of 1.6: 1, respectively, until a homogeneous gel-like mass is obtained, autoclave for 10-12 minutes, followed by a phased addition of all components to the mixer, homogenization until a homogeneous gel-like th mass and packaging in sterile syringes, with the following ratio of components in g / l: chlorhexidine bigluconate 0.05% - 8.0; metronidazole - 3.0; acrylic acid - 2.0; triethanolamine - 0.5; coltsfoot extract - 0.5; chlorophytum extract 0.5; extract of chamomile pharmacy - 0.5; birch bud extract - 0.5; large celandine extract - 0.5; nettle extract - 0.5; horseradish extract - 0.5; homogeneous gel-like mass of Kombucha - the rest, while the biomass of Kombucha culture (zoogley) is prepared as follows, using the culture obtained from the collection of pure cultures of VNII PB and VP, it is allowed to use zoogley on days 20-25 of cultivation Kombucha, zoogloeas piece in an amount of 0.8 kg / ³ 100dm finished drink is placed in a nutrient medium at the ratio zoogloeas nutrient medium and 1:10, respectively, the medium used, the infusion prepared from black tea and sugar sand in 1 dm ³ of culture medium, tea and sugar consumption of sand is 1.6 and 90 g, respectively, tea drinking water is poured at a temperature of 98 ° C, 1:50 and incubated 20-21 min, after which the resulting infusion is filtered through a sieve with pores with a diameter of 0.5 mm and sent to the reservoir for preparing the nutrient medium, add sugar and free drinking water at a temperature of 25 ° C, the mixture is thoroughly mixed, while the culture of Kombucha is grown at a temperature of 25 ° C under oxygen access open tank and for 10 days, then zooglie Kombucha in an amount of 400 g is homogenized with 250 ml of infusion of Kombucha until a homogeneous gel-like mass is obtained, the prepared semi-finished Kombucha is placed in sterile 250 ml glass vials, filled to half, closed with rubber stoppers and wrapped in aluminum caps, autoclave at a temperature of 132 ° C, a pressure of 2 atm for 20 minutes in a steam sterilizer SPVA75-1 NN (TRANS-SIGNAL), followed by storage until use (see US Pat. RU No. 2153816, IPC A23L 2/00, A23L 2/38, A23F 3/14). The resulting complex gel-like preparation for the treatment and prevention of acute mastitis in cows is used as follows.

With mastitis in cows, the drug is administered intracisternally: with subclinical, serous and catarrhal mastitis, 7 ml once a day for 5-7 days; with purulent-catarrhal mastitis - 10 ml once a day for 10 days, and before administering the drug from the diseased quarter of the udder, the secret is given out, and the nipple is disinfected, the drug is heated to room temperature before use and injected into the nipple of the affected quarter of the udder using a catheter . After the introduction, a light massage of the udder is conducted from the bottom up. For the prevention and treatment of inflammatory processes of the uterus in cows, sheep and pigs, the drug is administered intrauterine after delivery, surgical separation of the placenta, with postpartum endometritis and metritis-mastitis agalactia.

Before the introduction of the drug, sanitization of the external genitalia and tail root is carried out. If necessary, release the uterine cavity from inflammatory exudate.

The drug is injected into the uterine cavity using a Janet syringe or a POS-5 pig artificial insemination device and catheter: for therapeutic purposes, every 24 hours for 7-10 days, cows at a dose of 100 ml per animal, and sows and ewes at a dose of 35- 40 ml per 50 kg of body weight, for prophylactic purposes after giving birth or surgical separation of the placenta once - to cows at a dose of 100 ml per animal, sows and ewes at a dose of 25 ml per 50 kg of body weight.

The milk from the affected lobe of the udder is disposed of, then the biologically active points (BAP) are exposed to pulsed low-frequency current in the udder for 2 minutes with an interval of 12 hours before recovery. Cows recovered within three weeks. Mastitis prophylaxis: 5-6 days before calving, acupressure is performed in the lumbar and pelvic areas with a device, for example, Vocal-B, acting on biologically active points (BAP) with a pulsed low-frequency current for 1 min with an interval of 12 hours for 5 days then, from the first day after calving, antiseptic treatment of the nipples of the udder with the proposed preparation is carried out for 7 days after each milking, and for 5-6 days before transferring the cow to the general herd, acupressure is performed in the lumbar region, pelvis and udder with an instrument, for example "Vocals - In "Acting on biologically active points (BAP) with a pulsed low-frequency current for 1 min with an interval of 12 hours for 5 days.

Result: The obtained complex gel-like preparation was tested for the treatment and prophylaxis of acute mastitis in cows; cows recovered within twenty-one days.

Example 2. Carried out analogously to example 1, but take the components in the following ratio of components in g / l: chlorhexidine bigluconate 0.05% - 9; metronidazole - 3.5; acrylic acid - 2.5; triethanolamine - 1.0; coltsfoot extract - 1.0; chlorophytum extract - 1.0; chamomile pharmacy extract - 1.0; birch bud extract - 1.0; large celandine extract - 1.0; nettle extract - 1.0; horseradish extract - 1.0; homogeneous gel-like mass of Kombucha - the rest.

Result: The obtained complex gel-like preparation was used for the treatment and prevention of acute mastitis in cows; the cows recovered within fourteen days. The drug meets all the indicators of tables 1-5.

Example 3. Carried out analogously to example 1, but take the components in the following ratio of components in g / l: chlorhexidine bigluconate 0.05% - 13; metronidazole - 5.0; acrylic acid - 3.5; triethanolamine - 1.5; coltsfoot extract - 1.5; chlorophytum extract - 1.5; chamomile pharmacy extract - 1.5; birch bud extract - 1.5; large celandine extract - 1.5; nettle extract - 1.5; horseradish extract - 1.5; homogeneous gel-like mass of Kombucha - the rest.

Result: The resulting preparation was used for the treatment and prevention of acute mastitis in cows; the cows recovered within fourteen days. The drug meets all the indicators of tables 1-5.

Example 4. Carried out analogously to example 1, but take the components in the following ratio of components in g / l: chlorhexidine bigluconate 0.05% - 14; metronidazole - 5.5; acrylic acid 4.0; triethanolamine - 1.8; coltsfoot extract - 1.8; chlorophytum extract - 1.8; chamomile pharmacy extract - 1.8; birch bud extract - 1.8; large celandine extract - 1.8; nettle extract - 1.8; horseradish extract - 1.8; homogeneous gel-like mass of Kombucha - the rest.

Result: The obtained preparation was tested for the treatment and prophylaxis of acute mastitis in cows; the cows also recovered within fourteen days, but the consumption of components increased. The drug meets all the indicators of tables 1-5.

Thus, the most optimal examples are examples 2 and 3, since a drug with a given ratio of components gave a positive result in the shortest possible time.

Example 5. The study of the toxicological parameters of the drug, the determination of acute toxicity (see tab. 1, 5).

To determine the acute toxicity of the drug, the methodology described in the "Guidelines for the toxicological evaluation of new drugs for the treatment and prevention of non-communicable animal diseases" is applied, approved by V.T. Samokhin (1987). The experiment is carried out on white outbred mice. According to the analogue principle, 48 animals with a body weight of 22.0 ± 0.6 g were selected and 6 groups of mice were formed (n = 8), the watering and feeding of which was stopped 4 hours before the start of the experiment. The smallest toxic dose of the drug is determined by the most toxic drug in its composition - metronidozole. Mice of the first group in the stomach using a metal probe injected with 0.1 ml of the drug - 0.25 mg, animals of the second group - 0.2 ml, the third - 0.3, the fourth - 0.4 ml, the fifth - 0.5 ml, sixth - 0.6 ml. After administration of the drug, food is given after three hours. Observation of mice is carried out for 72 hours, taking into account activity, appetite, condition of the coat, and cases of death of animals are recorded.

The mice of the first, second, third, and fourth groups were slightly inhibited for 20 minutes after administration of the drug, strayed in a heap in the corner of the cage, and then behaved actively. After giving food, they ate with appetite. During the remaining time of observation, changes in behavior and general condition were not observed.

Mice of the fifth and sixth groups within 5 minutes after administration of the drug was observed inspiratory dyspnea, for 1-1.5 hours the mice were depressed, the hair was disheveled, strayed in a corner, the appetite was absent. The condition of the animals returned to normal within 3 hours.

No fatal cases were observed in any of the groups. The data obtained made it possible to attribute the proposed drug to the group of low-toxic drugs.

Example 6. The study of chronic toxicity of the drug (see table. 2).

In order to determine the chronic toxicity of the drug, an experiment was conducted on the accelerated determination of the cumulative effect. 20 nonlinear white mice weighing 18-25 grams were selected. Two groups are formed by the principle of analogues (n = 10). The drug is administered intragastrically using a metal probe daily. The mice of the control group were administered distilled water in the same manner. Within 4 days, the drug is given in a dose of 1000 mg / kg. The next four days, animals receive the drug at the rate of 2000 mg / kg. Within 9-15 days of the experiment, the dose of the drug is 4000 mg / kg. From day 15 to day 20, mice receive the drug at the rate of 8000 mg / kg. Observation is carried out daily throughout the entire period of the experiment. When assessing the condition of mice, the habit of animals, their activity, and appetite are taken into account. The clinical condition of the animals during the first and second periods of the experiment remained within the normal range, the mice were active, took food with appetite, and the coat was smooth. From the 9th day of the experiment, it was noted that the animal's hair became tousled, dull, the reaction to external stimuli was inhibited, the rats sat for a long time at the feeder, and then slowly began to eat. From the 15th day, the growth retardation of the mice of the experimental group became noticeable compared to the mice of the control group, the hair became sparse, tousled, the mice sat for a long time at the feeder, after which they slowly began to eat, and the fatness of the animals of the experimental group was below average. The condition of the rats in the control group throughout the entire observation period remained satisfactory.

The total average lethal dose with repeated administration was 88,000 mg / kg.

To determine the coefficient of cumulation using the formula:

K = LD ₅₀ ^x / LD ₅₀ ^o , where

K is the cumulation coefficient;

LD ₅₀ ^x - lethal average dose with repeated administration;

LD ₅₀ ^o - the average lethal dose with a single injection.

K _drug = 88000/10000 = 8.8

The cumulation coefficient is 8.8, which relates this drug to the fourth group - a weakly expressed degree of cumulation (see table 1).

Example 7. The study of the allergenic effect of the drug (see table. 3). The study of the allergenic effect of the drug is carried out by the method of cutaneous applications. For this, 2 groups of outbred rabbits were formed, 5 individuals in each. The rabbits of the first group are sensitized daily with multiple applications (n = 24), the drug in the same skin on the side with a diameter of 5 cm every 4 hours for four days. The second group (control) is sensitized with repeated applications (n = 24) of horse serum in 0.1 ml every 4 hours for 4 days in a row. After 72 hours (on the 7th day), drop samples are carried out. In the experimental group, use the drug according to the invention, in the control - horse serum. The reaction is taken into account every 24 hours, paying attention to the signs of the development of dermatitis in places of a drip test. As a result of the experiment, the absence of the allergenic effect of the drug was established.

Example 8. The local irritant effect of the drug

To determine the irritating effect of the drug, the method of conjunctival tests is used. To conduct a conjunctival test, three guinea pigs are used. Animals once in the conjunctiva under the upper eyelid of the left eye using a sterile pipette inject one drop of the drug according to the invention. The right eye serves as a control; one drop of distilled water is instilled into it. Analysis of the results is carried out after 30 minutes, 1, 3, 6, 12 and 24, 72 hours, recording the presence of outflows, hyperemia, density, color of the conjunctiva.

As a result of examination of guinea pigs, 30 minutes after administration of the drug, slight conjunctival hyperemia and moderate lacrimation are noted, which is natural when poorly soluble substances are introduced into the conjunctival sac. These changes gradually disappear after 2-5 hours. Subsequent examinations showed no signs of an inflammatory reaction, itching, or lacrimation. Based on the above results, it is concluded that the preparation according to the invention does not have a local irritant effect.

Example 9. Determination of antimicrobial properties of the drug.

To determine the antibacterial activity of the drug using the disk diffusion method. For the manufacture of disks, the drug is diluted with an equal amount of distilled water. One milliliter of the resulting suspension is used to impregnate 100 discs of filter paper. Next, the disks are transferred to a sterile Petri dish, which is placed in a thermostat for drying at a temperature of 37 ° C. Sowing a test culture of a field strain of staphylococcus is carried out on a dense nutrient medium meat-peptone agar. After plating under sterile conditions, discs impregnated with the preparation of the invention are placed on the surface of the agar. Diffusion of the drug into agar led to the formation of a zone of inhibition of the growth of microorganisms around the discs. After the plates are incubated in a thermostat at a temperature of 37 ° C for 48 hours, the result is taken into account by measuring the diameter of the zone around the disk in millimeters, which was 24 ± 1.6 mm, based on which it is concluded that the complex preparation according to the invention is quite active in against the field strain of staphylococcus.

The drug for the treatment and prevention of mastitis in cows according to the invention was tested on a farm in the Stavropol Territory.

The invention in comparison with the prototype and other known technical solutions has the following advantages:

- antimicrobial and anti-inflammatory broad-spectrum action;

- analgesic, regenerating, biostimulating, antiprotozoal and antibacterial action;

- excitation of immune defense mechanisms;

- simplification and cheapening of the method of preparation based on Kombucha, plant extracts and antibacterial components;

- a decrease in the body's response to histamine;

- relieving spasm of smooth muscles.

Claims (3)

1. A complex gel-like preparation for the treatment and prevention of mastitis in cows, containing antimicrobial and anti-inflammatory drugs, moreover, it contains metronidazole, chlorhexidine bigluconate 0.05%, biomass of Kombucha culture, and plant extracts as anti-inflammatory drugs components: coltsfoot, chamomile pharmacy, birch buds, large celandine, nettle, horseradish and chlorophytum, where propylene glycol is used as an extractant in a ratio of 1: 5, d additionally contains acrylic acid and triethanolamine in the following ratio, g / l: chlorhexidine bigluconate 0.05% 9-13 metronidazole 3,5-5,0 acrylic acid 2.5-3.5 triethanolamine 1.0-1.5 coltsfoot extract 1.0-1.5 chlorophytum extract 1.0-1.5 chamomile extract 1.0-1.5 birch bud extract 1.0-1.5 large celandine extract 1.0-1.5 nettle extract 1.0-1.5 horseradish extract 1.0-1.5 Kombucha biomass culture rest 2. The method of preparing a complex gel-like preparation for the treatment and prevention of mastitis in cows according to claim 1, which consists in mixing antimicrobial and anti-inflammatory drugs, homogenization, and it contains metronidazole, chlorhexidine bigluconate 0.05%, tea culture biomass as antimicrobial agents fungus, and as anti-inflammatory drugs - extracts of plant components: coltsfoot, chamomile, birch buds, celandine, nettle, horseradish and chlorophytum, and will complement acrylic acid and triethanolamine, moreover, the plant components are pre-dried, then each is homogenized in an amount of 1-1.5 g, poured with an extractant, which is used propylene glycol, in a ratio of 1: 5, additionally insisted for 14-15 days and filtered, Kombucha culture biomass is prepared, infused for 10-12 days, then homogenized with zooglium of Kombucha, diluted with 1.6: 1 Kombucha infusion, respectively, until a homogeneous gel-like mass is obtained, autoclave for 1 0-12 min followed by a phased addition of all components to the mixer, homogenization to obtain a homogeneous gel-like mass and packing into sterile syringes.