RU2212891C2 - Antiparasitic preparation with immunomodulating properties - Google Patents

Abstract

FIELD: veterinary science, pharmacology, biology. SUBSTANCE: an antiparasitic preparation comprises avermectin complex including avertin or abamectin, or aversectin C, or ivermectin and others as an antiparasitic agent. The preparation comprises ribav as an immunomodulating agent, ethyl alcohol as a solvent, polyethylene glycol-400 as a chelating agent and perlite as a carrier (adsorbent) being components are taken in the definite ratio. The preparation of proposed composition in oral application provides availability for treatment of animals of any species and enhances their productivity, shows 100% antiparasitic effectiveness and prevents inhibition of immune status. Invention is designated for treatment and prophylaxis of arachnoidal entomosis and nematodosis in domestic and wild animals and birds. EFFECT: enhanced effectiveness of preparation. 3 cl, 3 tbl, 8 ex

Description

 The invention relates to veterinary medicine, pharmacology, biology and is intended for the treatment and prevention of arachno-entomoses and nematodoses of domestic, wild animals and birds.

 Known agents for the treatment of parasitic diseases, including avermectins and carriers (1, 2, 3, 4, 5, 6, 7).

 The disadvantage of foreign and domestic injection forms based on avermectins is the suppression of the animal immune system for 2-3 weeks (8), the increased individual sensitivity of some animals, accompanied by local swelling at the injection site, passing through 3-7 days (9).

 The closest in technical essence to the claimed invention are preparations of the avermectin series for the prevention and complex treatment of diseases caused by endo-and ectoparasites of animals, containing the active principle from the mycelium Streptomyces avermitilis, pharmacologically acceptable carriers and immunostimulants (10, 11, 12, 13, 14) .

 When it is impossible to use injectable or skin preparations (this applies to horses, birds, fur and other animals, including wild ones), oral dosage forms that also have immunosuppression are used (15, 16).

 The aim of the present invention is to provide a preparation for oral administration in a mixture with food, both individual and group methods, possessing not only a high antiparasitic activity, a wide spectrum of action, but also an increased immunomodulating effect, a simplified method of using the drug, with an increase in the species composition of animals to be treatment, and increase their productivity.

 The solution to this problem is achieved by introducing the avermectin complex obtained from Streptomyces avermitilis VKPM S-1440 into the composition of the powder in the form of a powder, but the avermectin complexes used in other medicines, referred to as either avertin, aversectin C, or abamectin, or avermectin, or doramectin, or other active substances based on avermectin. As an immunomodulating agent that increases the resistance of the host organism and animal productivity, either ribav or other immunocorrectors are used); as an auxiliary substance, perlite (other fillers can be used), polyethylene glycol, ethyl alcohol and distilled water at component ratios, wt.%, are given in table. 1.

Avermectin complex is produced by soil microorganisms Streptomyces avermitilis, belonging to a number of avermectins from the group of macrocyclic lactones. It consists of 4 main (B _1a , B _1B , A _1a , A _1B ) and 4 minor (B _2a , B _2B , A _2a , A _2B ), closely related components. The expressed antiparasitic action is possessed by the components of group B.

 An avermectin complex from the Streptomyces avermitilis VKPM-S-1440 strain was used to produce an antiparasitic drug that does not possess immunosuppression, but exhibits high parasitocidal activity. Avermectin complexes can be used equally: either aversectin C, or abamectin, or ivermectin, or doramectin, or doramectin, or other

 All avermectin complexes in a very low therapeutic dose of 0.2 mg / kg body weight have a wide spectrum of antiparasitic activity.

 Ribav is an alcoholic extract of the synthesis products of microscopic endophytic fungi, containing a balanced complex of amino acids, peptides, enzymes, phosphorus-containing compounds, vitamins, lipids, pigments and other biologically active substances. In nature, products of endophytic fungi are designed to ensure vital activity and create healing properties in medicinal plants.

 Ribav possesses immunostimulating, wound healing, anti-inflammatory, hepatoprotective activity, helps to increase the body's natural resistance and activates antibody production during vaccination; stimulates erythropoiesis, metabolism and motility of the gastrointestinal tract. Ribav has a growth-promoting and anti-toxic effect in recommended doses.

Ethyl alcohol is a solvent. Miscible in all ratios with water, ether, chloroform, glycerin; boils at 78 ^o C (13, 14).

 Perlite-perlite expanded sand and gravel from the Aragat deposit (Armenia) is the carrier (adsorbent) (18).

 Polyethylene glycol-400 is a good complexing agent, which is often used as a component of the dosage form (12, 13).

 From the sources of information available to the applicant, the indicated set of essential features is not known, which makes it possible to obtain the indicated technical result, therefore, the claimed invention meets the patentability condition “novelty”.

 The applicant does not know means of a similar purpose, in which the distinguishing features of the claimed invention would be disclosed with the use of it in any combination of features of the specified technical result. Therefore, the claimed invention meets the condition of patentability "inventive step".

 Evidence of industrial applicability is claimed in the following examples.

 Example 1. In a mixer with a capacity of 50 l with constant stirring, pour 1.2 kg of polyethylene glycol - 400, 18.8 kg of a 75% alcohol extract containing 150 g of avermectin complex, 1.5 l of ribave, 5 kg of perlite, mix another 15 -20 minutes and leave the moistened mixture for 14 hours, after which it is dried. It turns out 7 kg of dry preparation.

 Example 2. Similar to example 1, only ribava add 2.0 liters.

 The antiparasitic composition is tested on ruminants (sheep, goats, deer, camels, cattle, etc.), horses, carnivores (dogs, cats, arctic foxes, etc.), rabbits, birds (chickens, geese, ducks, etc.) against larvae of gadflies, scabies mites, lice, small phages, fleas, nematodes of various species.

 Example 3. Use 20 calves spontaneously infected with strongilata of the gastrointestinal tract and larvae of hypodermis of the first stage. 5 animals mixed with group feed feed the antiparasitic composition abictin (commercial name) at a dose of 10 mg / kg; 5 - 5 mg / kg; 5 - avertin in a dose of 1 ml / 50 kg of animal weight; 5 calves do not receive the drug and serve as a control.

 10 days after treatment against strongilates and 7 months against gadfly larvae, they received a 100% effect against all types of parasites in calves of groups I, II and III. In control animals, in feces samples there were 374.5 ± 35.5 eggs of nematodir, 2732.0 ± 864.3 eggs of strong species of other species, and in April from 4 to 13 gadfly gnats were found on all back calves.

 Example 4. Use 4 groups of 20 sheep spontaneously infected with mites of sarcoptes, larvae of nasopharyngeal gadfly, dictiocaul, strongilata of the gastrointestinal tract and trichocephalus: sheep of the first group were fed abiktin containing ribav daily at 7 mg daily for 7 days at a dose of 10 mg / kg ; the second is 5 mg / kg; the third injected avertin at a dose of 1 ml / 50 kg of animal weight twice with an interval of 10 days.

 After 20, 30 and 60 days after the first injection, they received a 100% effect in the treated sheep of all experimental groups. The sheep of the control group still remained 100% infected with ecto- and endoparasites.

 Example 5. Of the 15 pigs spontaneously invaded by roundworms, esophagostomes, trichocephalus, strongyloids and hematopins, 3 groups were formed: pigs of the first group received 50 mg / kg abictin with food, and the second - 60 mg / kg. Pigs of the third group did not receive the drug and served as a control.

 10 and 20 days after treatment, all treated animals were free from invasion, and the control remained infected.

 Example 6. Of the 15 foals, spontaneously invaded by parascarides, strongilates of different species, strongyloids, larvae of nasopharyngeal and gastric gadfly, 3 equal groups were formed. The foals of the first group received abictin at a dose of 3 mg / kg with food, the second - 5 mg / kg twice with an interval of 24 hours. Animals of the third group of the drug were not received and served as a control.

 When the results were taken into account, after 20 days they got a 100% effect against nematodes and gadfly larvae, the animals of the control group remained infected.

 In the following experiments, the immunomodulatory effect of abictin was evaluated.

 Example 7. Used 25 lambs of five months of age, spontaneously infected with strongilata of the gastrointestinal tract, of which 5 equal groups were formed. Lambs of the first group were given abictin at a dose of 10 mg / kg (0.2 mg / kg in terms of DV), the second - ribav in a dose of 1 ml per head, the third - abictin in a dose of 5 mg / kg (0.1 mg / kg in DV ), the fourth abictin without ribava at a dose of 10 mg / kg (0.2 mg / kg in terms of DV). Animals of the fifth group did not receive the drug and served as a control. Studies were carried out for 3 months. The kinetics of T-lymphocytes are presented in table. 2. In animals of the control group, the relative number of T-lymphocytes gradually decreased and by the end of the experiment reached 15.2 ± 1.6%; in animals of the fourth group, a tendency to decrease in their number to 30 days after treatment was observed, then the number of T-lymphocytes increased and was higher than the control infected by 1.3 times until the end of the observation. In animals of the second group, a gradual increase in T-lymphocytes was noted throughout the entire period of research, and by day 90 it amounted to 28.8 ± 2.9%. In animals of the first and third groups, the number of T-lymphocytes was 2.5-2.6 times higher than in the control and amounted to 37.6 ± 3.9 - 39.4 ± 4.2%. The most stable increase in the number of T-lymphocytes was observed in lambs of the first group.

 Kinetics of B-lymphocytes. In the lambs of the control group, the number of B-lymphocytes decreased until the end of the observation (Table 3). In animals of the fourth group, a decrease in B-lymphocytes was initially observed, however, from day 60 their number increased by 1.4 times, in animals that received ribav, a slight increase in B-lymphocytes was noted, and by the end of the experiment their number was 20.4 ± 2.1 %; in animals treated with abiktin with ribav, already on the 7th day after treatment, an increase in the number of B-lymphocytes was noted by 1.4 times, and by the end of the experiment - 2.1-2.2 times.

Heterophilic agglutinins. In the animals of the control group, throughout the entire period of research, a steady decrease in the titer of natural antibodies occurred from log ₂ 3.0 ± 0.2 to log ₂ 1.6 ± 0.1 at the end of the experiment.

In animals treated with abictin, in the first days of observation, a decrease in antibody titer was noted from log ₂ 3.0 ± 0.2 to log ₂ 2.2 ± 0.1 on day 15, and then titers increased and by the end of the experiment they were log ₂ 3.1 ± 0.2.

 An increase in hemagglutinin titer was observed in animals treated with ribav and abiktin with ribav. However, in animals treated with abictin with ribav, antibody titers were at a higher level than in animals treated with ribav only.

 At the end of the experiment, all animals were killed and a helminthological study of the gastrointestinal tract was performed. In animals of the control group, 178.5 ± 20.1 gemonkhov, 120.4 ± 13.2 ostertagia, 39.9 ± 4.2 nematodir and 2728.2 ± 281.3 trichostrongil were found. In animals that received abictin with ribav, helminths were not found; those who received only abictin - there were single instances of helminths, those who received ribav - the number of helminths was as in the control.

 The use of a complex antiparasitic drug (abiktin + ribav) prevents and treats strongilatoses by 100% and increases the immune status by 2 times.

 Example 8. Economic efficiency was taken into account on 24 infected calves, of which 3 groups were formed: the first was prescribed abictin, including an immunomodulator, at a dose of 10.0 mg / kg, the second abictin without an immunomodulator at a dose of 10.0 mg / kg, the third group served as a control . Animals infected with 100% mixed types of nematodes of the gastrointestinal tract were weighed before giving the preparations and after 30, 60 and 90 days (Table 4).

 The weight gain of calves that received abictin without ribav was 22.3, and abiktin with ribav - 71.2 kg. The difference between the treated animals was 48.9 kg in favor of treatment with abiktin with ribav.

 Thus, the antiparasitic composition of the proposed composition, which includes an avermectin complex and an immunomodulator, has not only a wide spectrum of high antiparasitic action, but also prevents immunosuppression, simplifies the method of application and increases the productivity of animals without special economic costs.

Literature
1. William C. Campbell. Ivermectin and abamectin. / New York, Berlin, Heidelberg, London, Raris, Tokyo, 1989, p. 1-25, 114-124.

 2. RF patent 2054483, 1993.

 3. RF patent 2054848, 1996.

 4. Berezkina S.V., Golovkina L.P., Drinyaev V.A., Yurkiv V.A., Volkova G.N. Natural avermectins for the treatment of ecto- and endoparasites of animals Master. Conf. "Systematics, taxonomy and fauna of parasites", M., 1996. - P.15-16.

 5. Golovkina L.P., Berezkina S.V. Antiparasitic preparations based on S. aversectin // Vetinform, 1998, - 1 - С.4.

 6. RF patent 2124895, 1999.

 7. RF patent 2146147, 2000.

 8. RF patent 2149007, 2000.

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 10. The effect of ivomek and pharmacin on the indicators of the immune response in animals // Veterinary Medicine, 1998. - 5. - P.29-31.

 11. Mashkovsky M.D. Medicines - M. Medicine, 1984. - T. 1. - S.376.

 12. Brief chemical encyclopedia, MSE, 1961. - V. 5. - S.964.

 13. Pharmacist Handbook. M .: Medicine, 1981. P.12, 16-24.

 14. State Pharmacology of the USSR, 1968, 10th ed., S. 644-646, 905.

 15. Golovkina L.P., Volkova G.N., Kruglyak E.B. et al. Efficiency of a department for nematodoses of chickens // Veterinary Medicine, 2000, 5. P.30-33.

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 17. Manual on the use of rabava for domestic animals 13-5-2 / 664, 1996, C.1-2.

 18. GOST 10832-91.8

Claims (3)

 1. Antiparasitic drug with immunomodulating properties, including an avermectin complex and excipients, characterized in that it additionally contains an immunocorrector ribav in the following ratio of components, wt. %: avermectin complex 1.0-3.0 (2.0); riboids 5.0-20.0 (10.0); excipients - the rest.  2. The antiparasitic preparation according to claim 1, characterized in that the avermectin complex contains either avertin, or abictin, or aversectin C, or ivermectin.  3. The antiparasitic preparation according to claim 1, characterized in that it comprises an avermectin complex from Streptomyces avermitilis mycelium VKPM S-1440 (avertin) with a high content of group B avermectins.

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