UA146754U - VETERINARY IMMUNOSTIMULATING DRUG "BIOGLUCK" - Google Patents

Abstract

Veterinary immunostimulating drug contains as active substance polysaccharides - beta-glucan in combination with biotin, and the excipient is a 5% glucose solution.

Description

The useful model belongs to the field of veterinary medicine, in particular to pharmacology, immunology and epizootology, namely, it concerns drugs with immunostimulating action for the prevention and treatment of immunodeficiency conditions in animals, and can be applied by veterinary medicine specialists in veterinary clinics and farms of various forms of ownership in order to increase protective reactions of the animal body, restoration of their functional state and health.

Immunostimulants are drugs whose action is aimed at strengthening the body's immune response. They include not only pharmacological drugs, but also various bioadditives, adjuvants and other agents that accelerate or increase the intensity of immune processes.

Of course, the need to stimulate the strengthening of the body's protective reactions arises in conditions that are accompanied by suppression of the functional activity of the effector cells of the immune defense. At the same time, secondary immune deficiency can arise as a result of various diseases and become the main etiopathogenetic factor, lead to the manifestation of clinical signs of the disease, the development of opportunistic infections, as well as the emergence of resistance to antibacterial drugs.

According to the clinical experience accumulated to date, the treatment and prevention of most diseases and their complications are considered more effective when immunotherapy methods are included. In particular, the ability of immunostimulating drugs to increase the body's general resistance, to accelerate regeneration processes is the basis for their widespread use in complex therapy of immunodeficiency states, infectious and infectious-inflammatory diseases, to accelerate reparative processes, etc.

Currently known immunostimulating drugs (Meaning with interferon-inducing and immunomodulating (immunostimulating) activity, patent NO Me 2033157; MIimmunostimulator, patent NO Mo 2124894; Veterinary implantable drug with immunostimulating action (variant), patent VO Mo 2219910; Immunostimulating agent, patent NO2 Me2 3480 ; Immunostimulating agent, patent KO Mo 2510277; Therapeutic and preventive agent of immunostimulating action "Immunoton", patent of Ukraine Mo 12229; Method of manufacturing immunostimulator "Biekstrin", patent

Ukraine Mo 116896) contain arbidol as an active substance; glycyram; melatonin or melatonin with ximedone; nanodiamond powder and gold-modified nanodiamond powder; alcoholic tincture of plant collection (herb and inflorescences of purple echinacea, buds of common pine, roots and rhizomes of the high delusion, roots of bare licorice and grass of common harmala); water-alcohol extracts of roots and rhizomes of Eleutherococcus, roots and rhizomes of Echinacea purpurea, sugar syrup, St. John's wort; an extract made from immunocompetent organs of chickens and drone brood larvae.

The disadvantages of the above-mentioned known means are that some of them (patent VO Mo 2480223) require expensive and scarce components, others, which contain plant components or are made from organs and tissues of animals, are difficult to dose and can cause side reactions (patent VO Mo 2510277, patent of Ukraine 12229, patent of Ukraine Mo 116896) or have certain restrictions for use in various types of animals (patent VO Mo 2219910), or have no data on their effectiveness for use in veterinary medicine (patent VO Mo 2033157, patent VO

Mo 2124894).

The closest analogue in essence to the proposed useful model is an immunostimulating drug (patent KO Mo 2189825), which contains a fraction of polysaccharides with a molecular weight of 10-420 kD, obtained from the mushrooms Rieitgoii5 oziteeaish5.

The disadvantages of the closest analogue include the unstable composition of the drug, the lack of data on its side effects on the body and its effectiveness when used in animals.

The proposed drug and the closest analogue have significant common features, namely the use of polysaccharides as an active ingredient.

The proposed drug eliminates the indicated shortcomings of the closest analogue and provides a quick recovery of both local and systemic immunity, with a minimum of possible side effects, has antioxidant properties, has anti-inflammatory and anti-allergic effects, stimulates regenerative processes in the body.

The useful model is based on the task of developing a new veterinary immunostimulating agent that has no side effects on the body and is effective in the prevention of diseases associated with a decrease in the protective reactions of the animal body and for use in complex therapy to increase immunity in the treatment of diseases of various etiologies .

The task is solved by the fact that the veterinary immunostimulating drug contains polysaccharides as an active active substance, according to a useful model, beta-glucans are used as the main active substance in combination with biotin, and a 5-9b glucose solution is used as an auxiliary substance, with the following ratio of components, 90: beta-glucan From biotin 0.0005 96 glucose solution the rest.

Widely used today, natural immunostimulants, unlike synthetic ones, do not have a toxic effect on the body and are characterized by a minimal risk of developing 5 adverse reactions. Products based on beta-glucans fully meet these requirements. In addition to activating the phagocytic function of macrophages, beta-lucans potentiate the synthesis of mediators and biologically active substances - lymphokines, interferons, and immunoglobulins with the help of the same macrophages. Under the influence of beta-glucans, the concentration of immunoglobulin A in the blood plasma increases, which provides local immunity, beta-glucans have a regulatory effect on all subpopulations of leukocytes, and therefore on the immune system.

Beta-glucans are representatives of polysaccharides of Y-glucose monomers, connected by means of beta-glycosidic bonds, and differ among themselves in molecular weight, density and three-dimensional structure. The most active form of beta-glucans is beta-1,3/1,6-glucan, in the molecule of which glucose is attached to positions 1 and 3, the molecule has branches in positions 1 and 6.

Beta-glucans are large molecules that do not undergo enzymatic fragmentation in the gastrointestinal tract, are captured by the cells of the intestinal mucosa and are actively transported to the submucosal layer, where they activate macrophages, and through them - lymphocytes responsible for the protection of the endothelium, i.e. for local immunity . Thanks to the mechanism of repopulation, activated lymphocytes from the intestinal mucosa disseminate to the mucous membranes of various organs, providing protection against infections. Macrophages are activated on the surface of macrophages, which bind only to the unbranched part of the beta-glucan molecule, and the body's immune defense is implemented. The phagocytic function of macrophages is activated and cytokines, which are a signal for other cells of the immune system, in particular T-lymphocytes, epidermal cell growth factor, are increasingly synthesized and released. Some of the beta-glucans enter the liver through the portal vein, where they are captured by Kupffer cells, which, in response to interaction with polysaccharides, secrete cytokines that activate systemic immunity. Therefore, beta-glucans activate both local immunity (protecting the body against invasion of antigens) and systemic immunity (destruction of foreign genetic material and restoration of immune homeostasis). A distinctive feature of the immunomodulating action of beta-1,3/1,6-glucan is that it is adequate

From increasing the activity of the immune system without its excessive stimulation.

Rational medicinal correction of the functional activity of the immune system is a necessary measure for many diseases and pathologies. It is appropriate and reasonable to use activators (endotoxins, viruses, bacteria) of the primary link of immunity - macrophages, but it is not always highly effective and safe. In turn, compounds of beta-1,3/1,6-glucan and beta-1,3(0)-glucan are safe and can be used both enterally and parenterally. This pharmacokinetic feature of beta-glucans. Stimulation of regeneration processes through the activation of keratinocytes and fibroblasts is a local effect of beta-glucans.

Biotin (vitamin H, vitamin B7) is a water-soluble vitamin of group B. In the body, biotin plays an important role in the metabolism of carbohydrates, fats and proteins and is vital for the normal growth and development of cells. When ingested, biotin acts as a coenzyme of carboxylase, exerts an insulin-like effect and participates in the process of gluconeogenesis (due to participation in the synthesis of glucokinase), in connection with which it contributes to the stabilization of blood sugar, improves the function of the nervous system. Biotin is a synergist of other B vitamins, folic acid, pantothenic acid, and cyanocobalamin. There are data on the participation of biotin in the synthesis of purine nucleotides. Biotin is also a source of sulfur that participates in the synthesis of hemoglobin and collagen protein, which determines the feasibility of its additional introduction into the body to accelerate reparative processes.

Glucose is used as a solvent, which is completely absorbed by the body, being easily absorbed in the intestines. Glucose is nutritious and safe for a healthy body. It is during the oxidation of this substance that energy is released, which is necessary for the work of the body's organs and systems. It is used against poisoning and stress. This is a universal anti-toxic agent that helps with infectious diseases. Glucose maintains the volume of circulating plasma, helps to fill the balance of liquid and readily available elements necessary for the vital activity of the body. It easily penetrates into all cells of the body, which is why it is valued in medicine. The glucose solution increases the pressure in the cells, activates the main metabolic processes.

Stimulates the work of the liver, kidneys, heart, activates the production of many hormones and enzymes.

Getting into the blood, it gives a feeling of peace and stability. In addition, the immunomodulatory effect of glucose was found.

For oral use, glucose is given to patients, injured and during the recovery period. In addition, it is used in antibiotics and other medicines. Suitable for diluting some medicines and as a sweetener in medicines.

Thus, the given information explains the technical result of the proposed tool.

The veterinary immunostimulating drug "Biogluk" is made for oral use by mixing the components of the solution in the appropriate proportions, 90: polysaccharide beta-glucan With biotin 0.0005 5 96 glucose solution to 100.

In the conditions of the vivarium of the Lviv National University of Veterinary Medicine and Biotechnology named after S.3. Hkytsky conducted research on 20 healthy ants, from which one control and three experimental groups were formed (I group immunosuppression without immunostimulator;

II group - without immunosuppression with an immunostimulator; Group I - immunosuppression with an immunostimulator) 5 individuals in each group.

Maintenance, feeding, care and all manipulations with the mice were carried out in accordance with

by the European Convention "On the Protection of Vertebrate Animals Used for Research and Other Scientific Purposes" (Strasbourg, 1986).

For immunosuppression, the corticosteroid hormone dexamethasone was used in immunosuppressive doses of 0.05-0.5 mg per 1 kg of animal weight. To do this, twice with an interval of every 7 days, the animals of the I and III experimental groups were injected subcutaneously with the drug "Dexafort" based on dexamethasone of prolonged action (Ipietpei ZsPegipa-Riotsdy Apitai! Neanj, The Netherlands).

As an immunostimulant, the drug "Biogluk" (the proposed useful model) was used at the rate of 30 mg of beta-glucan per kg of mass, which was administered orally once a day for 14 days to animals of the II and I experimental groups after the second injection of "Dexafort".

Medical immunosuppression, "Biogluk" intake and weekly blood sampling for hematological studies were carried out: - the first blood sampling - the first administration of "Dexafort" to animals of the I and III research groups; - after 7 days - the second blood sampling - the second administration of "Dexafort" to the animals of the I and I experimental groups - they began to parenterally administer "Bygluk" to the animals of the II and II experimental groups; - 7 days - the third blood sampling - the reception of "Biogluk" was continued for the animals of the II and I research groups; - after 7 days - the fourth blood sample - the reception of "Biogluk" is stopped;

From - in 7 days - the fifth blood sample.

Hematological studies were carried out in the private veterinary laboratory "Neolab" of the FOP

Dmitrieva I.V. (Lviv, Ukraine). The number of erythrocytes and leukocytes was determined by the method of counting them in the Goryaev chamber, the hemoglobin content was determined by the hemoglobin method. The leukogram was derived based on the counting and differentiation of 100 leukocyte cells in blood smears stained according to the Romanovsky-Giemza method. At the same time, the size of the cells, the size and shape of the nucleus, the presence and color of grains in the cytoplasm were taken into account. Hematocrit value was determined using hematocrit capillaries by centrifugation for 10 min at 3000 rpm, erythrocyte sedimentation rate (1 hour) - using Panchenkov pipettes.

The digital material was statistically processed using a computer program

Mystozoia Ehsei from the package Mystozoia ONise 2007. Probability was determined according to the I-criterion.

Hematological studies have established that in animals ! in the experimental group, which received "Dexafort" subcutaneously twice with an interval of 7 days, the number of leukocytes probably decreased to 4.0220.31 (Р«0.05) from 5.41-40.03 G/l in the control. Morphological indicators of the blood of ants of the research group, immunosuppression with "Dexafort" without an immunostimulator (Met, n-5) is shown in Table 1.

Table 1

Continuation of table 1

Basophilisdei | (0... YUB0 B .B.0 1 Bzhyuzh (0 1 0 | 0 indicator

Note. In this and the following tables, the probability of differences with the control group: 7 -P«e0.05; 5 -

P«0.001; Z - erythrocyte sedimentation rate

The number of lymphocytes decreased from 36.76:247.74 (control) to 34.20x1.24; 33.80:51.74; 32.80-1.71 95 (Р«0.001) in animals of experimental groups. An increase in rod-nucleated and segmented neutrophils was established, respectively, to 8.20::0.20 and 44.40:2-0.93 from 7.08:0.29 9b and 35.52:50.15 95 in animals of the control group .

In the animals of the II experimental group, which were given "Biogluk", changes in the morphological composition of the blood were noted until the number of leukocytes and lymphocytes increased without the manifestation of signs of inflammation.

The morphological parameters of the blood of ants of HER research group, without immunosuppression with an immunostimulator (Mat, n-5) are shown in Table 2. This indicates an increase in the body's resistance function and confirms the immunostimulating effect of beta-glucan. The number of leukocytes in the animals of the II experimental group increased significantly (P<0.001) to 8.565-40.62 G/l compared to the animals of the control group, in which the indicators were 5.4120.03 G/l. The number of lymphocytes increased, respectively, to 51,620.51 95 (Р«0.001) from 36.76x7.74 95. A probable decrease in the number of segmented neutrophils was observed from 35.52:50.15 95 (Р«0.001) to 26.8:- 1.02 Or.

Table 2

Continuation of table 2

Basophilizbe | (0 .Yu.BMBGKGBzhyuzh"Yu0 | 0 | 0 | 0 | 0 indicator

In the PI animals of the research group, which were subjected to medical immunosuppression with "Dexafort" with the immunostimulator "Biogluk", it was established that under the influence of "Dexafort" the number of leukocytes decreases to 4.0220.50 G/l from 5.4120.03 G/l, the number lymphocytes - up to 33.60x2.25 905 from 36.76-7.74 96. Morphological parameters of the blood of ants of the PS of the experimental group, immunosuppression with "Dexafort", with an immunostimulator (Met, n--5) are given in table 3.

After taking Biogluk, a probable increase in the number of leukocytes to 8.6:20.60 G/l (Р«0.001) from 5.41-0.03 G/l, an increase in the number of lymphocytes to 49.40x2.70 95 of 36 was noted ,76:57,74 95 and platelets - up to 253.00-22.63 G/l from 204.00-46.64 G/l in mice of the control group. The number of eosinophils probably decreases both after the introduction of "Dexafort" to 2,420.6 95 (P«0.001) and "Biogluk" to 3.8:-0.49 95 (P«0.001) from 5.8:-0.06 9 o in control.

Table C

Basophylicea | (0 .BBy..yy.0...yy1.YUB.ЦШХ0 1.701110 10 indicator

Leukocytes in the body of animals play a protective, trophic and transport role. The protective function of leukocytes is to provide cellular immunity. They also destroy decaying cells and regenerated cells of their own body, recognize and neutralize genetically foreign substances (microorganisms). Neutrophils perform the function of phagocytosis and cytotoxicity. They are significantly inferior to macrophages in terms of phagocytic activity and can capture only relatively small objects, which is why they are also called microphages. A more typical property of these cells is the secretion of aggression factors outward into the tissue fluid to destroy free pathogens. Neutrophils are the first to arrive from the blood to the location of the pathogen.

The occurrence of hyperthermia and intoxication in the early stages of inflammation, as well as the formation of purulent exudate and a restrictive wall around the focus of infection, is related to their activity.

Eosinophils, like neutrophils, are phagocytes and cytotoxic cells, their activity is specialized and closely related to the functioning of the mucous membrane immune system. One of the leading effector immune mechanisms of mucous membranes is the mechanism mediated by the activity of mast cells. Eosinophils, together with a direct damaging effect on the pathogen, act as a regulator of this mechanism, preventing its hyperactivation.

Therefore, under the condition of medicinal immunosuppression, "Biogluk" exhibits an active immunostimulating effect, which is confirmed by the results of the conducted studies.

Thus, against the background of drug immunosuppression, taking "Biogluk" ensures the acceleration of recovery of the body's immune status. This indicates an increase in the number of leukocytes, lymphocytes and a decrease in the number of segmented neutrophils. "Bioglyuk" is advisable to use in immunodeficiency states and under the condition of therapy with corticosteroid hormones.

Claims (1)

FORMULA OF THE USEFUL MODEL Veterinary immunostimulating drug containing as active ingredient Zo polysaccharides, which is distinguished by the fact that beta-glucan in combination with biotin is used as the main active substance, and as an auxiliary substance - 5 95% glucose solution, with the following ratio of components, 90: beta-glucan From biotin 0.0005 96 of the remaining glucose solution.