RU2699799C1 - Antiparasitic composition and a method for use thereof for treating parasitosis of ruminant animals - Google Patents

Abstract

FIELD: veterinary science.

SUBSTANCE: group of inventions relates to veterinary parasitology and represents an antiparasitic composition comprising a supramolecular complex of albendazole with arabinogalactan, a supromolecular complex of ivermectin with arabinogalactan, sodium salt of carboxymethyl cellulose (blanose) and water in the following ratio of components, wt%: supramolecular complex of albendazole with arabinogalactan in weight ratio of 1:10 – 3.0, supramolecular complex of ivermectin with arabinogalactan in weight ratio 1:10 – 0.3, carboxymethyl cellulose (blanosa) – 0.25, water – balance, and a method of using said antiparasitic composition for treating helminthiases of ruminant animals, comprising oral administration of an antiparasitic composition in dose of 0.6 ml/kg of body weight, once, individually.

EFFECT: use of the declared group of inventions enables higher clinical effectiveness in animal parasites.

2 cl, 3 tbl, 4 ex

Description

The invention relates to veterinary parasitology, and in particular to means and methods of treating parasitic diseases of animals.

Parasitoses of farm animals are ubiquitous and significantly reduce the productivity and quality of the products.

Mixed invasions in animals caused by endo- and ectoparasites are the most common form of parasitic pathology (M.A. Shikhalieva, M.I. Bittirova, S.Sh. Mantaeva Z.X. Yusupova S.Sh. Chilaev. Association of Parasites in Cattle and Goats in the North Caucasus Region Russian Parasitological Journal - 2014. - Issue 4. - P. 16-21; Marchenko V.A., Efremova E.A., Saitov V.R., Hayrapetyan A. R. Parasitocomplex of meat breeds of cattle in the farms of the Altai Republic // Veterinarian / Scientific production Twain Journal -. Kazan.- №.4 - 2015. - S. 50-55).

The causative agents of arachnoentomiasis and helminthiases as components of parasitocenoses live on hosts in various associations, causing a multi-vector harmful effect. Parasitic insects and ticks in combination with each other, as well as with helminths, cause the most severe disease course, which is characterized by a variety of negative effects on the host organism, leads to secondary immunodeficiency, disturbances in the mechanisms of macroorganism homeostasis (Chebyshev N.V., Epiphany E. A., Grishina EA Helminthiasis: organ-system processes in their pathogenesis. M., "Medicine". 1998, 236 p.). Therefore, the prevention and treatment of mixed helminthiases is one of the most urgent tasks of modern veterinary medicine.

Science and practice have gained considerable experience in the application in animal husbandry of various anthelmintics and antiparasitic agents belonging to various chemical groups. They belong to different classes of compounds and, as a rule, are effective against a certain range of parasites.

Albendazole (ABZ) and its dosage forms are widely used for the treatment of helminthiases. The drug is effective against nematodes, cestodes and trematodes. The disadvantage of albendazole is the relatively high therapeutic dosages for individual helminthiases (5-75 mg / kg of animal weight) and the need for a long course of treatment [Arkhipov I.A. Anthelmintics: pharmacology and use. - Russian Agricultural Academy, 2009. - S. 148-158]. ABA is also not effective against parasitic arthropods.

In recent years, new antiparasitic preparations have been developed and proposed for use, which have a wide spectrum of action against many endo - and ectoparasites of animals and birds. Among these drugs are anthelmintics containing ivermectin, which is a highly effective therapeutic agent against nematodes and ectoparasites, as the active substance (DV) (Miller TW et.all., 1979; Campbell WC, et.all., 1984; Campbell WC 1989) .

However, ivermectin-based injectable preparations that use substances such as glyceroformal, propylene glycol and polyvinylpyrrolidone as a solvent have several disadvantages. These dosage forms have a high viscosity, which complicates the injection, causes irritation and other reactions at the injection site, and as a result of precipitation of ivermectin in tissues can have a toxic effect on the animal organism. Also, the disadvantage of using ivermectin and its dosage forms is the limitation of the spectrum of its antiparasitic action, the anthelmintic does not have an anti-cestodose effect and is not effective in trematodoses of animals.

Known drugs and methods of their use for treating animals, including albendazole or ivermectin in combination with other antiparasitic agents and in various forms (P RF No. 2294196 of 02.27.2007, P RF No. 2469716 of 11/10/2011), "The effectiveness of prazivera in sheep parasitoses " // HER. Belova, K.M. Sadov, I.A. Arkhipov, Russian Parasitological Journal, 2010, No. 3, p. 93-97).

However, the angelic preparations in these compositions have low bioavailability, since the active substance in them is in native form, without preliminary mechanochemical preparation and the substance used as a filler (CMC) provides a fairly short-term stabilizing effect of aqueous anthelmintic suspensions, which requires additional costs for accelerating the deworming process.

With the development of a new scientific direction in pharmacy - nanotechnology, a unique opportunity has arisen to design new dosage forms based on microcolloids, micelles, liposomes and microemulsions (Kwon G.S., 2003; Goodsell D.S., 2004). Based on these studies, it became possible to create a new dosage form of ivermectin, convenient to use, non-toxic in therapeutic doses and effective against endo- and ectoparasites even after a single use of the drug.

Known drug Niklomek, the supramolecular complex Niklomek includes ivermectin and niclosamide. However, the synthetic polymer polyvinylpyrrolidone (PVP) was used as a filler (E. Engasheva. Toxicological evaluation of the supramolecular preparation Niklomek obtained by mechanochemical technology // International Journal of Veterinary Medicine - 2016. - No. 4. - P. 42-45).

The disadvantage of this drug is that its anthelmintic efficacy against cestodes is determined only in laboratory animals and its effectiveness against parasitic insects has not been studied.

Known drugs and methods of their use for the treatment of animal helminthiases based on physiological water-soluble polymers containing supramolcular albendazole as an angelic , Yu.S. Chistyachenko, A.V. Dushkin, and others J. Chemistry in the interests of sustainable development. - 2015. - No. 5. - S. - 567-577).

However, these drugs also have a limited spectrum of action - only on intestinal helminthiases, and also do not always contain polymers that contribute to the optimal prolongation of the antiparasitic properties of angelmintics.

The closest solution adopted for the prototype is a drug based on albendazole and a method for its use in mammalian helminthiases (see P RF No. 2546535 of 04/10/2015, A61K 31/00).

However, a significant drawback is the limited range of effects of the angelic preparation albendazole (only on intestinal parasites), as well as the insufficient stability of the formed aqueous suspensions when using only one of the physiological excipients.

The objective of the invention is to expand the arsenal of antiparasitic agents and methods for the treatment of helminthiases and ectoparasitoses of ruminants.

The essence of the method lies in the fact that the antiparasitic composition comprising the supramolecular complex of albendazole with a water-soluble polymer arabinogalactan, according to the invention, in addition, the supramolecular complex of ivermectin with arabinogalactan is used as an anthelmintic, and in addition, the carboxymethyl cellulose sodium salt has the following ratio: . %: albendazole - 3.0, ivermek - 0.3, arabinogalactan - 1:10, carboxymethyl cellulose (blanose) - 0.25, water the rest.

The essence of the invention also lies in the fact that in the method of treating helminthiases of ruminants, including the oral administration of an antiparasitic preparation according to the invention, the antiparasitic composition according to claim 1 is used as an antiparasitic preparation in a dose of 0.6 ml / kg of animal weight, once, individually .

Examples of carrying out the invention.

1. Obtaining an antiparasitic composition.

To obtain the antiparasitic composition, the well-known anthelmintics were used - Albendazole (ABZ) and Ivermectin (Iver) in the form of supramolecular substances with a water-soluble polymer arabinogalactan (AG). Albendazole in the form of an intermolecular complex (ABZ with AG) was obtained by the method of mechanochemical technology (according to the method of S.S. Halikov et al., See P RF No. 2546535 dated 04/10/2015).

The intermolecular complex of ivermectin with arabinogalactan (Iver with AG) was obtained in a similar way using mechanochemical technology, including the processing of a mixture of solid components by intense mechanical stresses, realized in impact-grinding mills. Upon receipt of supramolecular complexes, mixtures of the substance ABZ with arabinogalactan and IVER with arabinogalactan were taken in weight ratios of 1:10.

In the dry claimed angelic compositions (ABZ with AG) and (IVER with AG), the ground carboxymethyl cellulose sodium salt was added. The resulting mixture was thoroughly mixed until a homogeneous mass, which is a dry suspension concentrate, ready for use. Water was added immediately before administration of the drug to the animals, then the container was shaken until a stable aqueous suspension was formed.

The introduction of carboxymethyl cellulose (blanose) into the sodium salt was due to the fact that this substance stabilizes and increases the viscosity of the dosage form of the composition, increases the effect of optimal prolongation of the active substance.

Determination of the optimal formulation of the antiparasitic composition is illustrated by the following examples.

Example 1. To prepare an antiparasitic composition, the blanose was ground in a mortar. Then, the supramolecular complex Iver with AG — 0.6 g, ABZ with AG — 6.0 g, crushed blanose — 0.36 g were placed in the specified proportions in the specified proportions, and water was added to a volume of 200 ml. The resulting mixture was thoroughly mixed to obtain a uniform suspension. However, the resulting suspension was not stable during storage and within 60 minutes after preparation was stratified into two fractions.

Example 2. To prepare an antiparasitic composition, the blanose was ground in a mortar. Then, the supramolecular complex Iver with AG - 0.6 g, ABZ with AG 6.0 g, crushed blanose - 0.5 g were placed in the specified proportions in the specified proportions, and water was added to a volume of 200 ml. The resulting mixture was thoroughly mixed to obtain a uniform suspension. The resulting suspension remained stable for 4 hours.

Example 3. To prepare an antiparasitic composition, the blanose was ground in a mortar. Then, the supramolecular complex Iver with AG - 0.6 g, ABZ with AG - 6.0 g, crushed blanose - 0.7 g were placed in a container in predetermined proportions, and water was added to a volume of 200 ml and water was added to a volume of 200 ml. The resulting mixture was thoroughly mixed to obtain a uniform suspension. The obtained suspension as well as in example 2 was stable during storage, however, we consider the use of blanose in this amount not appropriate.

Example 4. For the preparation of an antiparasitic composition (without blanose), the supramolecular complex Iver with AG - 0.6 g, ABZ with AG 6.0 g were placed in a container in predetermined proportions and water was added to a volume of 200 ml. The resulting mixture was thoroughly mixed to obtain a uniform suspension. However, the resulting suspension was not stable during storage and within 30 minutes after preparation was stratified into two fractions.

Thus, that for the preparation of an antiparasitic composition, the most optimal ratio of active substances and auxiliary components is reflected in example 2, which is calculated on the basis of mass. % was: albendazole - 3.0, ivermec - 0.3, arabinogalactan - 1:10, carboxymethyl cellulose (blanose) - 0.25, the rest was water.

2. Determination of the effectiveness of the active substances (ABZ and IVER) of the proposed drug for various parasitoses of sheep

The study of parasitocidal efficacy in intestinal helminthiases was carried out from July 2 to July 17, 2017 in the Shebalinsky district of the Altai Republic at the flock of sheep of an individual entrepreneur Chichinova V.Yu.

Against the background of selected invasive animals, the experimental and control groups were formed according to the principle of analogues of 10 goals, the control 20 goals. Before setting up the experiment, all animals were weighed and rejected.

The preparations were given individually to the sheep in the form of an aqueous suspension orally at a dose of 0.6 ml / kg of animal weight (mf), from a syringe with a rubber tube to the root of the tongue, compositions of mechanically modified preparations in a dosage of 0.2 mg / kg m for ivermectin were used. g. and albendazole based on DV 1, 2, 3 mg / kg m.

Basic (official) preparations of ivermectin and albendazole (without arabinogalactan) were used in the control groups in the form of aqueous suspensions in dosages of 0.2 mg and 2 mg per kg mf. respectively.

After the use of drugs, no visible toxic effects on animals were found.

Fifteen days after the experiment, 20 sheep of the control group were examined using the Fulleborn method of ovoscopy with eggs counted in the VIGIS chamber. As a result of the study, the following results were obtained - the animals were infected with intestinal strongilates by 95.0% with an AI of 949.3 i / g. f., moniesis infection of animals was 25.0% with IO 475.4 I / g f., trichocephalus - 10.0%, with IO 9.5 i / g. f. All animals of the control group were infected with imagoes of sheep’s bloodsucker, with AI - 11.0 specimens (Table 1-3).

The generalized test results of drugs with strong gastrointestinal tract gastrointestinal tract (GIT) sheep are presented in table 1.

_mm ^* - mechanically modified

As a result of setting up an experiment to evaluate the effectiveness of the compositions of mechanically modified preparations of ivermectin and albendazole for gastrointestinal tract strictiloses, it was found that the extensivity (EE) of various dosages of the compositions was in the range of 68.5-100%, and the intensification efficiency (IE) was 96.2-100%.

The parasitocidal effectiveness of the applied dosages of the basic drugs ivermectin and albendazole was significantly lower and amounted to EE - 57.9%, IE - 98.2% and - EE - 15.8%, IE - 93.0%.

In general, the composition with a dosage of ivermectin _mm 0.2 and albendazole _mm 2-3 mg per kg of mf, which EE was 89.5 - 100%, IE - 99.4 - 100%, can be considered the most acceptable.

The test results of the preparations for moniesiosis of sheep are presented in table 2.

_mm ^* - mechanically modified

The table shows that the effectiveness of the composition of mechanically modified preparations of ivermectin and albendazole with moniesiosis in various dosages in terms of extensibility was in the range from 20 to 100%, and the intensity from 76.4 to 100%.

The use of basic drugs in dosages of ivermectin and albendazole, respectively 0.2 and 2.0 mg / kg m. turned out to be ineffective.

Taking into account the assessment of effectiveness in intestinal strictile infections, the composition of ivermectin _mm 0.2 and albendazole _mm 2 mg per kg m.

The test results of the preparations for melophagosis of sheep are presented in table 3.

_mm ^* - mechanically modified

The table shows that the effectiveness of the composition of mechanically modified preparations of ivermectin and albendazole with melophagosis in the tested dosage in terms of extensibility was 90.0%, and the intensity was 92.8%. The effectiveness of basic ivermectin was 1.3 times lower and amounted to 70.0%, while the initial albendazole did not demonstrate an entomocidal effect.

The experiments on evaluating the effectiveness of the compositions of mechanically modified preparations of ivermectin and albendazole using arabinogalactan with the addition of carboxymethyl cellulose (blanose) as an excipient in the composition for intestinal helminthiases and ectoparasitoses (melophagosis) showed a significant advantage of this composition over the initial forms.

The most acceptable in terms of effectiveness can be considered a composition with a dosage of ivermectin _mm 0.2 and albendazole _mm 2-3 mg per kg m.zh., the extensivity of which with mixed helminthiases (strongylitis and moniesiosis) was 89.5 - 100%, IE - 99.4 - one hundred%.

The composition of mechanically modified preparations of ivermectin and albendazole with melofagosis at a dosage of ivermectin _mm 0.2 and albendazole _mm 2 mg per kg mf turned out to be quite effective. with indicators of EE - 90.0% and IE - 92.8%.

Claims (6)

 1. An antiparasitic composition comprising a supramolecular complex of albendazole with arabinogalactan, a supramolecular complex of ivermectin with arabinogalactan, sodium carboxymethyl cellulose (blanose) and water in the following ratios of components, wt.%: - supramolecular complex of albendazole with arabinogalactan in a weight ratio of 1:10 - 3.0, - supramolecular complex of ivermectin with arabinogalactan in a weight ratio of 1:10 - 0.3, - carboxymethyl cellulose (blanose) - 0.25, - water the rest.  2. A method of using an antiparasitic composition for the treatment of ruminant helminthiases, comprising oral administration of an antiparasitic composition, characterized in that the antiparasitic composition according to claim 1 is used at a dose of 0.6 ml / kg of animal weight, once, individually.