RU2414902C1 - Bactericidal composition for prevention and treatment of infectious diseases of hoofs in animals - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to veterinary. Bactericidal composition for prevention and treatment of infectious diseases of hoofs in animals, includes stabilised sol of copper, zinc and silver nanoparticles, methylene blue, as well as polyethyleneglycole-4000, polyvinylpyrrollidone, cellulose, formic and lactic acids, purified water with specified component ratio.

EFFECT: invention ensures increase of anti-microbial activity and improvement of composition storing terms.

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Description

The invention relates to veterinary medicine, in particular to substances used for the treatment and prevention of infectious diseases of hooves.

The proposed bactericidal composition includes, as pharmacologically active agents, a stabilized sol of copper, zinc and silver nanoparticles, and methylene blue as an antiseptic.

The use of the composition can increase the therapeutic effect and reduce treatment time.

DESCRIPTION OF THE INVENTION

This invention relates to the field of veterinary medicine and relates to the treatment and prevention of infectious diseases of animal hooves.

The formation of large livestock complexes everywhere contributed to the spread of infectious diseases, such as necrobacteriosis, hoof rot (interdigital phlegmon), persistent hoof rot (interdigital dermatitis). This was due to replenishment of farms with animals, including those received from abroad.

Necrobacteriosis is an infectious disease characterized by purulent-necrotic lesions of the skin and underlying tissues (often on the lower parts of the limbs), mucous membranes, and sometimes parenchymal organs. The disease is found everywhere, but especially often in areas of developed sheep and reindeer husbandry. The causative agent of this disease is the bacterium Fusobacterium necrophorutn - a polymorphic microbe, motionless, gram-negative, does not form spores and capsules, is a strict anaerobic, grows well on nutrient media. Widely distributed in the external environment. Sources of the causative agent of the infection are sick, ill and clinically healthy animal carriers of bacteria. Bacteria of necrosis - the permanent inhabitants of the rumen and intestines of ruminants - are stored in the body of rodents for months. They are excreted into the external environment with feces, with saliva, and from patients - with necrotic tissues. Infection of animals usually occurs through damaged skin and mucous membranes (in young animals with teething, through the umbilical cord). Contamination is facilitated by stubble pasture on damp, swampy pastures, long hauls, and feeding of dry and prickly roughage.

Hoof rot, or interdigital phlegmon, is an infection of the soft tissue between the toes. Hoof rot is caused by the anaerobic bacterium Fusobacterium necropborum. Anaerobes of Dicbelobacter (Bacteriodes) nodosus and Prevotella melaninogenicus are also involved in the development of the disease. Bacteria infect the skin of the legs in the damaged areas and initially cause painful swelling between the fingers. In sick animals, lameness on one or several limbs, swelling of the skin of the interdigital gap are noted. With the development of the inflammatory process, erosion and ulcers appear in the tissues of the interdigital gap, exfoliation and putrefactive decay of the horn of the hoof wall and sole begin, and sometimes the hoof bones are exposed. The exudate released in this case has a specific fetid odor. Drying, it forms a crust. With such tissue damage, animals lie more, they develop exhaustion, and wool productivity decreases.

Persistent hoof rot, or interdigital dermatitis, is a chronic inflammation of the skin between the toes (in the interdigital gap). Caused by the bacterium Dichelobacter nodosus. The affected area of the skin takes a swollen appearance due to the drying exudate, forming a crust. This condition causes lameness, cracks in the heel of the hoof or its erosion.

Currently, there are several ways to treat and prevent hoof disease.

One of the most common is the use of antibiotics (tetracycline, lincomycin, spectinomycin, penicillin, etc.). These substances are delivered to the affected areas using foot baths, aerosol spraying, and leg wraps. Despite the high effectiveness of antibiotics, their use has several disadvantages. So, these drugs are expensive, their use in the treatment of dairy cows can lead to the presence of antibiotic residues in meat and milk. There is also the likelihood of the appearance of a strain of bacteria that are resistant to these antibiotics with prolonged treatment.

In the treatment of infectious diseases of the hooves, formaldehyde is used. Formaldehyde solutions are used as an aerosol, in the form of foot baths, as well as in the composition of ointments (RU 2347560 C2). But this method is ineffective, and the use of formaldehyde is limited due to its toxicity.

Herbicides (copper and zinc compounds, peroxides, etc.) were used as a means of combating and preventing hoof rot and necrobacteriosis. But such compositions for treatment are recommended only in high concentrations, so they irritate the hooves and healthy areas of the skin.

Known aqueous composition based on a copper salt, additionally containing a quaternary ammonium compound and peroxide (RU 2235546 C2). The disadvantage of this composition is the use of mineral and organic acids necessary to maintain a pH level of 1.6-2.0, which are irritating in contact with unaffected areas.

Closest to the claimed result achieved, selected as a prototype is a pharmaceutical composition with antimicrobial activity, containing copper and zinc as a pharmacologically active agent in chelated form (http://provet.ru/shop/UID_1084.html). When exceeding the permissible concentration of copper and zinc salts, the remainder of these salts may be in milk and meat of cows. Also, the disadvantages of this tool include its high cost.

The problem solved by the invention is the preparation of a pharmaceutical composition having high antimicrobial efficacy, a wide range of suppressed microflora and a minimum of side effects in the treatment and prevention of infectious diseases of hooves.

The technical result from the use of the invention is to increase antimicrobial activity and minimize side effects when using the drug.

This result is achieved by the fact that the bactericidal composition for the prevention and treatment of infectious diseases of hooves, containing a base - polyethylene glycol-4000, polyvinylpyrrolidone, cellulose, acids and purified water, contains pharmacologically active agents as a stabilized sol of silver, copper and zinc nanoparticles, as an antiseptic - methylene blue in the following components, wt.%:

Polyethylene glycol-4000 9.0-14.0 Polyvinylpyrrolidone 15.0-20.0 Cellulose 1.0-3.0 Stabilized Sol of Copper Nanoparticles 3.0-6.0 Stabilized Sol of Zinc Nanoparticles 3.0-6.0 Stabilized Sol of Silver Nanoparticles 3.0-6.0 Lactic acid 0,0-1,0 Formic acid 0,0-1,0 Methylene blue 0.1-0.2 Purified water Up to 100

According to current data, the mechanism of the biological effect of copper, zinc and silver on a pathogenic microorganism cell consists in the sorption of the ionized metal by the cell membrane, penetration into and inhibition of the respiratory chain enzymes, as well as the separation of oxidation and oxidative phosphorization processes in the cell, as a result of which the cell dies. In addition, copper and zinc have a healing effect, accelerate the recovery of blood vessels, damaged skin areas.

After application, the composition creates a film having good adhesion to the surface.

The basis of the product also has the additional function of transporting the active substances of the ointment deep into the infected area.

The technological process for preparing the agent for treating and preventing fungal skin diseases is carried out in a reactor equipped with a combined stirrer, a heating / cooling jacket and an external homogenizer with a recirculation loop. The process proceeds at a temperature of 50 to 20 ° C with continuous homogenization and evacuation. Evacuation allows to reduce the oxygen content in the preparation to a minimum, as a result of which the possibility of oxidation of active substances sharply decreases and, accordingly, the shelf life of the claimed preparation increases.

Packing means is made on a filling machine in plastic tubes of 200 g.

Production safety is stipulated by the relevant sections of the regulation and safety instructions. To ensure sanitary standards, the premises where the product is manufactured, packaged and packaged are equipped with forced-air and exhaust ventilation, air conditioning and bactericidal UV lamps. According to the degree of fire and explosion hazard, the production of the product belongs to category “B”, according to sanitary design standards - non-toxic, according to the rules of electrical installations - non-explosive. There are no by-products, wastewater, and air emissions from the manufacture of the drug.

The resulting preparation has a soft gel-like consistency, translucent, blue with a weak specific odor, pH from 5.5 to 6.0.

Example 1. Preparation of the composition (calculated per 100 wt.%)

59.5 wt.% Water is loaded into the reactor for the preparation of the composition, a stirrer and heating are turned on. 9.0 wt.% Polyethylene glycol-4000 (PEG-4000) is loaded into the water heated to 50 ° C in small portions with the stirrer working. Stir until a homogeneous solution. By starting cold water into the jacket of the reactor, the solution is cooled to a temperature of 20-25 ° C, the homogenizer is turned on, and 4.0 wt.% Stabilized sol of copper nanoparticles (SZNChM) and 5.0 wt.% Stabilized sol of zinc nanoparticles (SZNZhC) are loaded into the reactor, 1.0 wt.% Lactic acid, 0.5 wt.% Formic acid, 19 wt.% Polyvinylpyrrolidone (PVP), 1.8 wt.% Cellulose and 0.2 wt.% Methylene blue. Homogenization is carried out until a homogeneous mass is obtained, the homogenizer is turned off and the ointment is packaged.

Example 2

Analogously to example 1, but with the following ratio of components:

water 57.7 wt.%; PEG-4000 12 wt.%; SZNChM 4.0 wt.%; SZNChTS 5.0 wt.%; lactic acid 1 wt.%; formic acid 1 wt.%; PVP 18.0 wt.%; cellulose 1.2 wt.%; methylene blue 0.1 wt.%.

Example 3

Analogously to example 1, but with the following ratio of components:

water 59.5 wt.%; PEG-4000 12 wt.%; SZNChM 4.0 wt.%; SPZNS 4.0 wt.%; lactic acid 1 wt.%; PVP 17.0 wt.%; cellulose 2.3 wt.%; methylene blue 0.2 wt.%.

Example 4

Analogously to example 1, but with the following ratio of components:

water 58.9 wt.%; PEG-4000 14 wt.%; SZNChM 4.0 wt.%; SPZNS 4.0 wt.%; lactic acid 0.5 wt.%; formic acid 0.5 wt.%; PVP 16.0 wt.%; cellulose 2.0 wt.%; methylene blue 0.1 wt.%.

Example 5

Analogously to example 1, but with the following ratio of components:

water 59.0 wt.%; PEG-4000 14 wt.%; SZNChM 3.0 wt.%; SZNChC 3.0 wt.%; SPZNS 3.0 wt.%; lactic acid 0.5 wt.%; formic acid 0.5 wt.%; PVP 15.0 wt.%; cellulose 1.8 wt.%; methylene blue 0.2 wt.%.

Example 6

Analogously to example 1, but with the following ratio of components:

water 58.3 wt.%; PEG-4000 10 wt.%; SZNChM 3.0 wt.%; SZNChC 3.0 wt.%; SPZNS 3.0 wt.%; formic acid 1.0 wt.%; PVP 20.0 wt.%; cellulose 1.5 wt.%; methylene blue 0.2 wt.%.

The study of the antibacterial activity of the claimed drug was carried out by diffusion into agar on solid nutrient media by analyzing the zones of inhibition of test microorganisms (ATCC) used for the antimicrobial action of drugs. Studies were carried out for the following standard strains of microorganisms: Fusobacterium necrophorutn, Dicbelobacter (Bacteriodes) nodosus, Prevotella melaninogenicus. For comparison, the activity of the antifungal prototype was determined (Example 7).

The test results (table) indicate that due to the synergistic action of copper, zinc and silver nanoparticles, the patented composition exhibits significantly stronger antifungal properties than the prototype agent for all studied standard strains.

The results of the study of antibacterial activity of drugs. Objects of research The number of destroyed bacteria,% Fusobacterium necrophorutn Dicbelobacter (Bacteriodes) nodosus Prevotella melaninogenicus Example 1 97.9 ± 0.3 98.3 ± 0.2 97.6 ± 0.2 Example 2 98.1 ± 0.1 97.7 ± 0.3 97.9 ± 0.1 Example 3 97.5 ± 0.5 96.0 ± 0.2 98.1 ± 0.4 Example 4 98 ± 0.2 97.1 ± 0.4 98.0 ± 0.2 Example 5 99 ± 0.2 98.2 ± 0.2 98.6 ± 0.2 Example 6 98 ± 0.5 98.6 ± 0.3 99.3 ± 0.3 Example 7 (prototype) 46.7 ± 0.5 52 ± 0.3 48.4 ± 0.1

Claims (1)

A bactericidal composition for the prevention and treatment of infectious diseases of hooves in animals, containing a base - polyethylene glycol-4000, polyvinylpyrrolidone, cellulose, pharmacologically active agents, acids and purified water, characterized in that it contains stabilized sol of silver, copper and zinc nanoparticles as pharmacologically active agents , as an antiseptic - methylene blue in the following ratio of components, wt.%:
Polyethylene glycol - 4000 9.0-14.0 Polyvinylpyrrolidone 15.0-20.0 Cellulose 1.0-3.0 Stabilized Sol of Copper Nanoparticles 3.0-6.0 Stabilized Sol of Zinc Nanoparticles 3.0-6.0 Stabilized Sol of Silver Nanoparticles 3.0-6.0 Lactic acid 0,0-1,0 Formic acid 0,0-1,0 Methylene blue 0.1-0.2 Purified water up to 100