RU2757490C1 - Acaricidal antimicrobial zooshampoo and method for its production - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: invention relates mainly to veterinary medicine, namely to detergents, zoo shampoos used for the treatment and prevention of fungal and bacterial diseases, as well as for the control of acariform mites belonging to the type of arthropods to the class of arachnids to the order of ticks to the suborder Sarcoptiformes of the superfamily Sarcoptoidea - scabies mites. Acaricidal antimicrobial zooshampoo contains the following ratio of the starting components (wt%): n-hexadecyltriphenylphosphonium bromide - 0.01; 4,6-dinitro-5-chlorobenzofuroxan - 1.0; sodium laureth sulfate - 17.0; cocamidopropyl betaine - 5.0; cocamide diethanolamine - 1.0; distilled water - the rest. The method for obtaining acaricidal antimicrobial zooshampoo consists in the fact that first a soap base is prepared, for which 17.0 wt.% Sodium laureth sulfate, 5.0 wt.% Cocamidpropyl betaine, 1.0 wt.% Diethanolamine cocamide and distilled water are taken, stirred at room temperature until a homogeneous consistency is obtained; then a mixture of active ingredients is prepared, for which 1.0 wt% of 4,6-dinitro-5-chlorobenzofuroxan dissolved in ethyl alcohol is taken, 0.01 wt.% of n-hexadecyltriphenylphosphonium bromide dissolved in ethyl alcohol is added, the resulting mixture is stirred until a homogeneous consistency is obtained. Then a mixture of active ingredients is added to the soap base with constant stirring, stirring is continued until a homogeneous consistency is obtained. Then the mixture is heated to a temperature of 64.7°С, kept under stirring until the ethyl alcohol is completely evaporated and cooled at room temperature.

EFFECT: proposed acaricidal antimicrobial zooshampoo has a combined acaricidal, antibacterial and antifungal effect, has low toxicity to mammals and is highly effective against acariform mites, pathogenic skin fungi and bacteria.

2 cl, 1 dwg, 5 tbl, 6 ex

Description

The invention relates mainly to veterinary medicine, namely to detergents, zoo shampoos used to combat acariform mites belonging to the arthropod type, to the class of arachnids, to the order of ticks, the suborder Sarcoptiformes, the Sarcoptoidea superfamily - scabies mites, as well as for the treatment and prevention of fungi and bacterial diseases. Scabies mites are parasites of domestic and wild animals, cause microbial suppuration and scratching, localize inside or on the skin and cause a disease - scabies, which can be transmitted to humans.

The need for a complex acaricidal, antifungal and antibacterial action is due to the fact that mites enter into a symbiotic interaction with bacteria and fungi, as a result of which the skin affected by mites becomes a breeding ground for bacteria and fungi.

Further, the applicant presents the terms and the conceptual apparatus used in the claimed technical solution to eliminate contradictions and a more complete understanding of the essence of the claimed technical solution.

Acariform ticks are invertebrates belonging to the arthropod type (Arthropoda), the Chelicerata class, and the Acariformes order. They cause dermatitis, scabies, allergies, and can cause catarrhal conditions of the respiratory tract and gastrointestinal tract. [https: //bme.org/index.php/%D0%90%D0%9A%D0%90%D0%A0%D0%98%D0%A4%D0%9E%D0%A0%D0%9C% D0% 9D% D0% AB% D0% 95_% D0% 9A% D0% 9B% D0% 95% D0% A9% D0% 98].

Invasion - the penetration of parasites through the epithelial barriers of the host [https://ru.wikipedia.org/wiki/Invasion].

Sarcoptoses is a non-seasonal contagious (infectious) pruritic skin disease of animals caused by acariform ticks of the genus Sarcoptes. [https://ru.wikipedia.org/wiki/Sarkoptosis].

Notoedrosis (Notoedrosis) - acariasis of humans and domestic animals, characterized by skin irritation, itching.

Amitraz is an organic compound of synthetic origin belonging to the group of triazopentadiene compounds; is a member of the amidine family. It is the active substance of a number of drugs used in plant growing, animal husbandry and beekeeping as acaricides of systemic action [https://ru.wikipedia.org/wiki/Amitraz].

Amidin is a skin antiseptic and disinfectant containing ethyl alcohol [https://infodez.ru/product/view1/9512_amidin_akva.html].

The main objective of the claimed technical solution is the development of a domestic zoo shampoo for combating various types of scabies mites, as well as for the treatment and prevention of various fungal and bacterial infections in domestic and farm animals caused by exogenous infectious factors, and a method for producing the claimed shampoo.

This invasion causes significant economic damage, which consists of a decrease in the productivity of animals, a deterioration in the quality of the skin, the cost of carrying out therapeutic and prophylactic measures (Lashkova V.A. , A.N. Tokarev // Collection of scientific papers: Actual problems of veterinary medicine - No. 150. - St. Petersburg, 2019. - pp. 19-20).

The course of sarcoptic mange can be acute, chronic and latent, which in most cases is associated with insufficient effectiveness of the drugs used for treatment. The main clinical signs are itching, skin lesions, intoxication of the body and depression of the central nervous system. Therefore, the search for new domestic acaricidal drugs is relevant and timely as of the date of submission of application materials.

The essence of the claimed technical solution lies in the fact that a shampoo is used as an acaricidal and antimicrobial agent, which contains two active substances in the ratio (1): (2) = 0.01: 1, where:

(1) n-hexadecyltriphenylphosphonium bromide;

(2) - 4,6-dinitro-5-chlorobenzofuroxan.

(1)

(2)

From the investigated prior art, the applicant has identified the antimicrobial activity as such of the active substances included in the claimed shampoo.

So, the invention is known under the patent of the Russian Federation No. 2452477 "Antibacterial and antimycotic composition of a wide spectrum of action based on phosphonium salts and substituted benzofuroxan", the essence is an antibacterial and antimycotic composition containing quaternary phosphonium halide salts, based on tributyl and triphenylphosphines with higher halide alkyl 5,7-dichloro-4,6-nitrobenzofuroxan as active components in their equimolar ratio.

Also known is the acaricidal activity of the active substances included in the claimed shampoo, from the invention according to the patent of the Russian Federation No. 2497508 "Acaricidal pharmaceutical composition based on a salt of quaternary phosphonium, substituted dinitrobenzofuroxan and xymedonghydrochloride" , substituted dinitrobenzofuroxan, xymedone hydrochloride and dimethisulfoxide at a weight ratio of 0.1: 1: 10: 100, a 1% emulsion of this agent in dimethyl sulfoxide is used for treatment.

Analysis of the prior art investigated by the applicant showed that structural analogs of the claimed acaricidal antimicrobial shampoo for the treatment and prevention of fungal and bacterial diseases, as well as for the control of ticks based on quaternary phosphonium salts (1) and a mixture of two furoxans (2 and 3), on the date of filing the present application from the investigated prior art has not been identified.

In addition, no funds have been identified that would combine both antimicrobial and acaricidal properties, which is a very relevant factor. The applicant on the existing market did not reveal the presence of special detergents with the widest possible spectrum of action, while made in the form of a zooshampoo, applicable not only as a detergent, but also as a means to combat acariform mites, as well as for the treatment and prevention of fungal and bacterial diseases. At the same time, from the studied prior art, the applicant has not identified means available for a wide range of uses, including for the treatment of the population at an affordable price.

In this regard, one of the main tasks of the claimed technical solution is to create an effective non-toxic zoo shampoo, which would include both acaricidal and antimicrobial properties. Since the applicant from the investigated prior art did not identify combined detergents, acaricidal and antifungal agents were studied separately and their quality and consumer properties were compared in comparison with the claimed technical solution. Further, the applicant presents an analysis of the identified funds in the sequence indicated above.

Acaricidal agents

From the investigated prior art, the applicant identified the agent permethrin - a synthetic insecticide, acaricide, which belongs to the group of pyrethrins, natural insecticides contained in the flowers of the Aster family (chrysanthemums, asters). In low doses, pyrethrins act as repellents and repel insects. In higher doses, these compounds affect the nervous system of insects, disrupting the transmission of nerve impulses. This provokes insect paralysis and subsequent death.

So, the invention is known according to the patent of the Russian Federation No. 2409948 "Insecticidal composition Dis", the essence is an insecticidal composition for combating lice resistant to permethrin and pyrethroids at various stages of development, containing permethrin, nonionic oxyethylated surfactant, phenoxyethanol, acetic acid, shampoo " Apple ", characterized in that it additionally contains pyriproxyfen in the following ratio of components, wt.%:

Permethrin 0.2-1.5 Pyriproxyfen 0.001-0.1 Nonionic oxyethylated surface-active substance 1.4-10 Phenoxyethanol 3.0-9.0 Acetic acid 0.1-0.2 Shampoo "Apple" rest

The disadvantage of the known technical solution is that the metabolism of permethrin occurs mainly in the liver. The main enzyme involved in this process is glucoronosyltransferase. It is known that this enzyme is produced in the liver of a cat much less than in the liver of a dog or a person [Richardson, J.A. (2000). Permethrin spot-on toxicoses in cats. J. Vet. Emerg. Crit. Care 10: 103-106]. In this regard, the use of permethrin in shampoos for cats is unacceptable, as it can be fatal. Another disadvantage is the short duration of action of this component in the form of a shampoo.

The invention is known according to the application of the Russian Federation No. 97111096 "Insectoacaricidal preparation for combating animal ectoparasites Morinilin", the essence is an insectoacaricidal preparation for combating animal ectoparasites, containing amitraz and a hydrophobic base, characterized in that it additionally contains deltamethrin and dimethyl sulfoxide, and as a hydrophobic bases - polyethylene oxide with the following ratio of components, wt%:

Amitraz 0.2 - 1.0 Deltamethrin 0.005 - 0.02 Dimethyl sulfoxide 10 - 20 Polyethylene oxide rest

The disadvantage of the known technical solution is the risk of amitraz poisoning if the dosage is incorrect. It is known that most of the time amitraz poisoning in animals, especially in dogs and cats, is acute, bradycardia and hypotension are observed, in some cases, blood clots [Gupta, R. C. (2012). Amitraz. Veterinary Toxicology, 599-603. Doi: 10.1016 / b978-0-12-385926-6.00049-1]. Thus, the known drug has low efficacy when used as directed.

The invention is known according to the application of the Russian Federation No. 2006136805/15 from 17.03.2005 "Cream-gel containing Ivermectin", the essence in relation to the composition is a pharmaceutical composition based on a compound of the avermectin family in the form of a cream-gel, including in a physiologically acceptable medium, an oil phase dispersed in the aqueous phase with a polymeric emulsifier that is not a surfactant, said oil phase comprising oils with a melting point below 30 ° C and free of solid fats with a melting point above 30 ° C. The essence in relation to the method is a method of obtaining a composition according to any one of claims 1 to 17 at room temperature, comprising the following stages: a) the components of the fatty phase are mixed until the specified phase becomes homogeneous; b) the components of the aqueous phase are dissolved in water until complete homogeneity is obtained; c) the polymeric emulsifier and optional carbomer are dispersed in the aqueous phase until a homogeneous gel is obtained; d) with moderate stirring, the fatty phase is introduced into the homogeneous gel obtained in step c) so as to obtain an emulsion; f) mixing the components of the active phase; ivermectin is solubilized in the resulting mixture; the resulting phase is then introduced into the emulsion with moderate stirring; f) with moderate stirring, introduce the neutralizing agent in such a way as to obtain the desired pH value.

The main disadvantage of the known technical solution in relation to the composition is the neurotoxicity of the known preparation for animals, which can manifest itself in the form of depression of the central nervous system of mammals with subsequent ataxia.

The main disadvantage of the known technical solution in relation to the method is low manufacturability, high energy costs. In this case, the sequence of actions of the known method is significantly different from the claimed technical solution. Thus, based on the above, the known drug (cream-gel) has low efficacy when used as directed.

As of the date of submission of the claimed technical solution, the most effective, convenient and promising for practical use are oral preparations of the isoxazoline class. At the same time, it should be emphasized that from the studied prior art, in general, not a single case of development of resistance in ticks to these compounds has been identified, which is a fundamental factor for its intended use.

However, there is clearly insufficient data on the safety of known drugs in relation to use in animals at the date of submission of the declared materials. However, the US Food and Drug Administration (FDA) has issued a warning about potential side effects for these drugs [https://www.fda.gov/animal-veterinary/cvm-updates/animal-drug- safety-communication-fda-alerts-pet-owners-and-veterinarians-about-potential-neurologic Date of access: 30.04.2020]. It reported on the principal possible appearance of tremor, ataxia, various neurological seizures and seizures in dogs. Loss of appetite, general lethargy, vomiting and diarrhea were also recorded.

Antifungal agents

To combat and prevent various fungal infections, a number of shampoos with antifungal activity have been identified. Compounds such as chlorhexidine, triclosan, miconazole or ketoconazole are used as active substances.

Thus, the applicant has identified an invention under the patent US5776430A "Antimicrobial cleanser for topical use, containing chlorhexidine gluconate and alcohol", the essence is a broad-spectrum antimicrobial shampoo, where chlorhexidine is an external antiseptic and disinfectant containing:

(a) from about 0.65 to 0.85 wt. % chlorhexidine or a pharmaceutically acceptable salt thereof;

(b) from about 0.1 to 0.4 wt. % cetylactate or a pharmaceutically acceptable salt thereof;

(c) from about 50 to 60 wt. % ethanol;

(d) from about 1.0 to 2.0 wt. % emulsifying wax NF; and,

(e) aerosol propellant.

The disadvantage of the known technical solution is that the use of chlorhexidine as an active substance in a zooshampo has a number of limitations: the presence of sulfate surfactants inactivate chlorhexidine; for the manifestation of antimicrobial activity, the shampoo must be on the animal's coat for at least 7 minutes, which can cause dry skin and allergies.

The most effective component, according to the applicant, and often found in medicinal shampoos, is ketoconazole, an antifungal drug derived from imidazole.

From the investigated prior art, the applicant also identified a number of other technical solutions using ketoconazole as an active substance: inventions according to RF patents No. 2246291 "Shampoo based on ketoconazole", RF No. 2611410 "Shampoo for cleansing hair and scalp (options)", US7732450B2 " Topical Ketoconazole Antifungal Composition, EP0758879B1 Improved Anti-Dandruff Shampoo.

Due to the fact that ketoconazole is mainly used as a component of shampoo for humans, it was taken by the applicant as a benchmark in microbiological studies for comparison with the claimed technical solution.

Thus, from the studied prior art, no analogues of the claimed technical solution have been identified, both in relation to both the composition and the method of its production. Based on the foregoing, the independent claims are drawn up without a preamble.

The goals and technical result of the claimed technical solution is the creation of a fundamentally new domestic acaricidal and antimicrobial zoo shampoo and a method for its production, which has (zoo shampoo):

- combined acaricidal, antibacterial and antifungal action;

- low toxicity due to the optimally selected composition and ratio of active components and their low content in the declared shampoo;

- a convenient form of release in the form of a shampoo, involving the use of both a therapeutic and a prophylactic agent.

- high efficiency when used for its intended purpose in comparison with the world-known analogues at the date of filing the application with technical solutions.

The essence of the claimed technical solution is an acaricidal antimicrobial zoo shampoo, characterized in that it contains the following ratio of components, wt%:

n-hexadecyltriphenylphosphonium bromide 0.01 4,6-dinitro-5-chlorobenzofuroxan 1.0 sodium laureth sulfate 17.0 cocamidopropyl betaine 5.0 cocamide diethanolamine 1.0 distilled water rest

The method of obtaining acaricidal antimicrobial zooshampoo according to claim 1, which consists in the fact that first prepare a soap base, for which take 17.0 wt.% Sodium laureth sulfate, 5.0 wt.% Cocamidpropyl betaine, 1.0 wt.% Diethanolamine cocamide, the rest is distilled water, stirred at room temperature until a homogeneous consistency is obtained; then a mixture of active substances is prepared, for which 1.0 wt% of 4,6-dinitro-5-chlorobenzofuroxan dissolved in ethyl alcohol is taken, 0.01 wt% of n-hexadecyltriphenylphosphonium bromide dissolved in ethyl alcohol is added, the resulting mixture is stirred until a homogeneous consistency is obtained; then a mixture of active ingredients is added to the soap base with constant stirring, stirring is continued until a homogeneous consistency is obtained, then the mixture is heated to a temperature of 64.7 ° C, kept with stirring until the ethyl alcohol is completely evaporated; then the mixture is cooled at room temperature.

The claimed technical solution is illustrated in FIG. 1 to FIG. 5.

FIG. 1 shows Table 1, which shows the antibacterial and antifungal activity of active substances (1) and (2) (Example 2).

FIG. 2 presents Table 2, which shows the antibacterial and antifungal activity of the finished claimed acaricidal antimicrobial zooshampoo (Example 3).

FIG. 3 shows:

- Table 3, which shows the antibacterial and antifungal activity of the finished claimed acaricidal antimicrobial zoo shampoo after dilution;

- a graph that shows the values of the zone of inhibition of microbial growth (Example 4).

FIG. 4 shows Table 4, which shows the acaricidal effect of various concentrations of the claimed acaricidal antimicrobial zooshampoo on scabies mites (Example 5).

FIG. 5 shows Table 5, which shows the comparative efficacy of the claimed zooshampoo in comparison with known acaricidal agents for feline notoedrosis (Example 6).

Further, the applicant gives a more detailed description of the claimed technical solution , starting with the receipt of the initial components described in the identified by the applicant from information sources known as such.

The components of the claimed pet shampoo are prepared as follows .

N-hexadecyltriphenylphosphonium bromide (1) is obtained according to a known method [Starke Ch.M. Phase transfer catalysis. Chemistry, Catalysts and Applications / Ed. Ch.M. Starks. M .: Chemistry, 1991. - 157 p.].

4,6-Dinitro-5-chlorobenzofuroxan (2) is obtained according to a known method [Buzykin BI, Gubaidullin AT, Litvinov IA, Yusupov L.M. Butlerov Communications, 2005, 6 (2), 29-32].

Sodium laureth sulfate, cocamidpropyl betaine and cocamide diethanolamine are known per se) commercially available soap base components.

The claimed zoo shampoo is obtained by the claimed method according to the following main steps .

Stage 1. Preparation of a soap base from sodium laureth sulfate, cocamidopropyl betaine, diethanolamine cocamide and distilled water.

Stage 2. Preparation of a mixture of alcoholic solutions of active ingredients of n-hexadecyltriphenylphosphonium bromide (1), 4,6-dinitro-5-chlorobenzofuroxan (2).

Stage 3. Preparation of a ready-made pet shampoo by mixing a soap base and a mixture of active ingredients according to the stated sequence of actions.

Further, the applicant gives examples of the implementation of the claimed technical solution.

Example 1. Preparation of the claimed acaricidal antimicrobial zoo shampoo according to the claimed method

Stage 1. Preparation of the soap base

A soap base is prepared, for which they take 17 wt.% Sodium laureth sulfate (for example, 17 g), 5 wt.% Cocamidpropyl betaine (for example, 5 g), 1 wt.% Diethanolamine cocamide (for example, 1 g), the rest is distilled water (up to 100 wt.% Of the total mass of the shampoo, for example, 75.99 g), is stirred at room temperature until a uniform consistency is obtained, for example, on a magnetic stirrer.

Stage 2. Preparation of a mixture of active ingredients

The active ingredients are preliminarily dissolved in ethyl alcohol.

Take 1.0 wt.% 4,6-dinitro-5-chlorobenzofuroxan (for example, 1 g), dissolved, for example, in 10 ml of ethyl alcohol, add 0.01 wt.% N-hexadecyltriphenylphosphonium bromide (for example, 0.01 d), dissolved, for example, in 1 ml of ethyl alcohol. The resulting mixture is stirred until a uniform consistency is obtained at room temperature, for example, on a magnetic stirrer.

Stage 3. Preparation of ready-made pet shampoo

In the soap base prepared according to Stage 1, add with constant stirring, for example, on a magnetic stirrer, a mixture of active substances (1) and (2) prepared according to Stage 2, stirring is continued until a homogeneous consistency is obtained. Then the mixture is heated to a temperature of 64.7 ° C, for example, in a water bath, kept under stirring until the ethyl alcohol has completely evaporated. Next, the mixture is cooled at room temperature to obtain the claimed zooshampoo.

Further, the applicant provides examples of confirmation of the antimicrobial and acaricidal activity of the claimed zooshampoo.

Example 2. Study of the antimicrobial (antibacterial and antifungal) activity of active substances (1) and (2)

To study the antimicrobial properties of active substances (1) and (2), the sedimentation method of air research proposed by R. Koch was used.

This method consists in the cultivation of bacteria in the indoor air on nutrient media treated with the test substances. In accordance with this method, indoor air bacteria were cultured on nutrient media treated with an alcohol solution of active ingredients (1) and (2) at a concentration of 1%, followed by determination of the qualitative composition of pathogenic colonies.

The prepared agar nutrient medium in a sterile box was poured into sterile Petri dishes.

The study was carried out on the example of microorganisms E. Coli, B. Cereus, S. Aureus, Candida albicans.

To study the antimicrobial properties of a mixture of active substances (1) and (2), 5 drops of the mixture were added to the nutrient medium of each dish, inhabited by microorganisms, and distributed over the entire surface of the nutrient medium.

The dish was kept in a thermostat for 5 days at a temperature of 29-30 ° C, constantly monitoring the growth of colonies. A description of the cultural and morphological characteristics of the colonies in each Petri dish was made.

The results of measuring the antibacterial and antifungal activity of the mixture of active substances (AD) (1) and (2) are shown in Table 1 in Fig. 1.

From the data given in Table 1, it can be concluded that the mixture of active ingredients (1) and (2) of the claimed zooshampoo has high antibacterial and antifungal activity. Moreover, the specified activity is manifested in the prepared zooshampoo at a very low concentration of DW, within about 1 wt.% (See Examples and Figures).

At the same time, attention should be focused on the fact that the high efficiency of the claimed technical solution remains even with its significant dilution - by 2, 4, 8, 16, 32 and 64 times (at an AR concentration of 0.5 - 0.016 wt%, respectively - cm Table 3 in Fig. 3), taking into account the fact that the initial concentration of active substances is initially a value of slightly more than 1 wt.%. According to the applicant, this is evidence that the claimed technical solution is very effective when used for its intended purpose, since it is known from the studied prior art that analogs exhibit only a partial therapeutic effect (antibacterial and antifungal) at higher concentrations of active substances - from 0 , 2 to 3.0 wt.%, Namely:

chlorhexidine 0.65-0.85 wt% (US5776430A);

ketoconazole - 0.3-3.0 wt.% (RF No. 2246291)

ketoconazole or eubiol 0.3-3.0 wt% (EP0758879B1);

permethrin - 0.2-1.5 wt.% (RF No. 2409948).

Example 3. Study of the antimicrobial (antibacterial and antifungal) activity of the claimed acaricidal antimicrobial zooshampoo

To study the antimicrobial properties of the finished claimed zoo shampoo, the sedimentation method for studying the air of R. Koch was also used.

For control, a known shampoo containing 2 wt% ketoconazole was chosen.

The prepared agar nutrient medium in a sterile box was poured into sterile Petri dishes.

To study the antimicrobial properties of shampoos, 5 drops of 1% of the claimed zooshampoo and 2% shampoo with ketoconazole as a comparison were added to the nutrient medium of each dish inoculated with microorganisms, respectively, and distributed over the entire surface of the nutrient medium.

The cups were kept in a thermostat for 5 days at a temperature of 29 - 30 ° C, constantly monitoring the growth of colonies. A description of the cultural and morphological characteristics of the colonies in each Petri dish was made.

Data on the antimicrobial activity of 1% of the claimed acaricidal antimicrobial zooshampoo, as well as the 2% shampoo with ketoconazole taken as a comparison, are shown in Table 2 in Fig. 2.

From the data given in Table 2, we can conclude that the claimed zooshampoo, in addition to antifungal, exhibits antibacterial activity.

It can also be concluded that the claimed zoo shampoo exhibited an antifungal activity comparable to that of ketoconazole, while the content of active components in the claimed zoo shampoo is significantly (approximately two times) lower than in the shampoo with ketoconazole.

Example 4. Study of the antimicrobial (antibacterial and antifungal) activity of the claimed acaricidal antimicrobial zoo shampoo after dilution when used as directed

The use of shampoo is known to involve dilution with water, so it was important to determine the concentration at which an effective antibacterial effect would be achieved.

Solutions of the claimed acaricidal antimicrobial zoo shampoo were prepared by the dilution method.

Samples were prepared, diluted 2, 4, 8, 16, 32 and 64 times, respectively.

The studies were carried out similarly to Example 3.

The results are shown in Table 3 and in the diagram presented in Fig. 3.

From the data given in Table 3 and in the diagram (Fig. 3), it can be concluded that the most active in relation to pathogenic microflora were 1% and 0.5% solutions of zooshampoo.

This means that with a 1: 1 ratio of pet shampoo and water, the maximum possible therapeutic effect will also be achieved.

At the same time, one should pay attention to the fact that even when the shampoo was diluted 64 times, a pronounced antifungal effect was observed against Candida albicans, as well as an antibacterial effect against B. Cereus.

Tests with further dilution by the applicant were not carried out, however, from the data obtained, the applicant makes a logical conclusion that the claimed zooshampoo, in practical use, will have an antibacterial and antifungal effect outside the investigated concentrations.

This fact not only confirms the high therapeutic potential of the claimed zoo shampoo, but also has a positive effect on the economic components when used as directed.

Example 5. Study of acaricidal activity of the claimed acaricidal antimicrobial zoo shampoo against Psoroptes cuniculi ticks in vitro

The studies were carried out in vitro on isolated P. cuniculi ticks taken from spontaneously infested rabbits according to the method of V.I.Ilyashchenko. (Ilyaschenko V.I. Sarcoptoid mites, improvement of methods of diagnosis and control of them .: Author's abstract of thesis. Doctor of Biology, Sciences. S.-P., 1993. - 36 p.).

On filter paper, in a Petri dish, moistened with 1-2 ml of the claimed zooshampoo at a concentration of 0.005 to 1%, respectively, 20 live mites were placed and covered with a second sheet of paper soaked in the same shampoo.

The closed dishes were placed in a thermostat at a temperature of 30 ° C, while providing oxygen access.

The observation of ticks was carried out after exposure to the drugs in time: 10, 20, 30 minutes, 1, 2, 4, 24 and 72 hours after applying the drugs, respectively.

Served as control 20 mites placed on filter paper moistened with distilled water.

The research data are shown in Table 4 in FIG. 4.

From the data shown in Table 4, it can be seen that:

• 60 minutes after applying the declared pet shampoo:

- in 0.005% concentration 12 mites out of 20 turned out to be dead,

- in 0.01% concentration, 13 mites out of 20 turned out to be dead,

- in 0.05 - 1.0% concentrations of live ticks were not detected.

• 24 and 72 hours after the application of the claimed zoo shampoo in the concentrations used from 0.05 to 1.0 live mites were not detected - the declared zoo shampoo had a 100% acaricidal effect.

In the control (water), the ticks remained alive at all times of the study.

Example 6. Study of the effectiveness of the claimed acaricidal antimicrobial zoo shampoo in cats notoedrosis

Cats with notoedrosis caused by the causative agent Notoedres cati parasitizing the scalp were treated.

Before use, the claimed zoo shampoo was dissolved in water preheated to 30-35 ° C. The treatment was carried out by thorough washing - first, the affected areas of the head, where pathogens are localized, then the cats were washed completely.

The cats were divided into 3 groups (3 heads each):

- cats of the 1st group were treated with 0.05% of the declared zooshampoo at a dose of 0.5 ml, 2 times with an interval of 6 days.

- cats of group 2 were treated with control drugs for comparison - the drug "Ivermek spray", then 0.05% shampoo with ketoconazole at a dose of 0.5 ml, 2 times with an interval of 6 days.

- cats of group 3 were not treated (control).

The results of the studies were taken into account by examining the treated skin surface and examining the scrapings for the presence of an invasive beginning 7, 15 and 30 days after treatment, respectively.

The results are shown in Table 5 in FIG. 5.

From the data given in Table 5, it can be seen that before treatment, both Notoedres cati mites and eggs were found in skin scrapings of sick cats. Acarological examination of cats of group 1 7, 15 and 30 days, respectively, after treatment, adults and tick eggs were not found.

In cats of the 2nd group, on the 7th day after treatment, respectively, mite eggs were revealed in scrapings from the skin. In the subsequent periods of research, the results of acarological studies were negative.

Cats of the 3rd, control group were infected with notoedrosis at all times of the study.

Thus, from the above, it can be concluded that the applicant has achieved the goals and the claimed technical result , namely, a new highly effective domestic acaricidal and antimicrobial zooshampoo has been created and a method for its production has been developed. The claimed zoo shampoo obtained by the claimed method possesses:

- combined acaricidal, antibacterial and antifungal action;

- low toxicity due to the optimally selected composition and ratio of active components and their low content in the declared shampoo;

- a convenient form of release in the form of a shampoo, involving the use of both a therapeutic and a prophylactic agent.

- high efficiency when used for its intended purpose in comparison with the known analogues in the world at the date of filing the application technical solutions.

The claimed technical solution meets the "novelty" requirement of patentability for inventions, since at the date of the applicant's submission of application materials from the studied prior art, no sources have been identified that have a set of features identical to the set of features of the claimed technical solution.

The claimed technical solution is not obviously obvious to a person skilled in the analyzed field of technology. Moreover, the claimed technical solution makes it possible to solve a number of diverse problems, namely, in combination with a low concentration of active substances, the claimed zoo shampoo exhibits high antibacterial, antifungal and acaricidal activity. Thus, the claimed technical solution meets the “inventive step” criterion for inventions.

The claimed technical solution meets the criterion of "industrial applicability" for inventions, since The inventive zoo shampoo can be obtained by using well-known domestic components using standard equipment and known techniques.

Claims (3)

1. Acaricidal antimicrobial zooshampoo, characterized in that it contains the following ratio of the starting components, wt%: n-hexadecyltriphenylphosphonium bromide 0.01 4,6-dinitro-5-chlorobenzofuroxan 1.0 sodium laureth sulfate 17.0 cocamidopropyl betaine 5.0 cocamide diethanolamine 1.0 distilled water rest 2. The method of obtaining acaricidal antimicrobial zooshampoo according to claim 1, which consists in the fact that first prepare a soap base, for which take 17.0 wt.% Sodium laureth sulfate, 5.0 wt.% Cocamidpropyl betaine, 1.0 wt.% Cocamide diethanolamine and distilled water, stirred at room temperature until a homogeneous consistency is obtained, then a mixture of active substances is prepared, for which 1.0 wt.% of 4,6-dinitro-5-chlorobenzofuroxan dissolved in ethyl alcohol is added, 0.01 wt. % n-hexadecyltriphenylphosphonium bromide dissolved in ethyl alcohol, the resulting mixture is stirred until a homogeneous consistency is obtained, then the mixture of active ingredients is added to the soap base with constant stirring, stirring is continued until a homogeneous consistency is obtained, then the mixture is heated to a temperature of 64.7 ° C, kept with stirring until the ethyl alcohol is completely evaporated, then the mixture is cooled at room temperature.

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