Dioxidin veterinary instructions for use. Dioxidin for cats - indications and treatment regimen

The ever-increasing problem of providing the population of our country with good nutrition is mainly due to the low productivity of farm animals. This is due to a number of reasons and, in particular, the high morbidity and mortality of the latter. However, the main one is inadequate feeding of animals, which does not provide all the physiological needs of the body for biologically active substances of appropriate quality (I.V. Petrukhin, 1989, N.I. Kleimanov, 1987, etc.). In this case, the normal flow does not occur physiological processes in the organs and tissues of the body and, as a result, metabolism is disrupted, the productivity, growth and development of animals decreases, and various types of pathologies arise (V.T. Samokhin, 1981).

At the same time, even in conditions optimal feeding the majority of animals (up to 58%) grow slower than their physiological capabilities, and about 10% are sharply stunted (I.E. Mozgov, 1964).

Industrial technologies for livestock farming greatly aggravate this situation, because physical inactivity and disruption of connections with natural biotopes have led to a decrease in the digestibility of biologically active substances, and, consequently, to a greater need for them for the body (V.M. Danilevsky, 1980) .

Therefore, in countries with intensive livestock farming, pharmacological regulation of the physiological processes of the body is widely used using various substances that allow accelerating the growth of both satisfactorily and poorly developing animals on average: chickens by 12-20%, piglets - 12-17%, calves and lambs by 8-12% (A.M. Venediktov, A.A. Jonas, 1979). These drugs are called growth-promoting agents and their introduction is mandatory in so-called medicated or guaranteed feeds along with vital biologically active substances (vitamins, macro- and microelements, amino acids, etc.). These include mainly antibiotic drugs. (A.B. Arkhipov, 1984; M.N. Argunov, 1994; L.B. Safonova, 1997; A.I. Frolov, 1998).

They activate the functional activity of the body and its systems, mobilize its reserve capabilities and thereby accelerate the growth and fattening of animals (I.E. Mozgov, 1964, P.E. Radkevich, 1970).

IN last years Along with antibiotics, for such purposes antimicrobial chemotherapeutic agents of other classes of compounds and, in particular, drugs of the quinoxaline series are increasingly being used. The most famous of them is a drug developed by Bayer called Bayonox, the active ingredient of which is olaquindox triturate (D. Sechneider et al., 1970; “Anon” (Bayo-N-ox, 1978).

In our country, at VNIIFKhI, a scientific team led by E.H. Padeyskaya (1978) from quinoxaline derivatives developed and found quite widespread use of the drugs dioxidine and quinoxidine, which are produced in large volumes at the pharmaceutical association "October" (St. Petersburg).

These drugs have a different mechanism of action on the microbial cell than known drugs. Drug resistance to them develops more slowly and does not reach high limits. The use of quinoxalines in medical practice quite widely, but it is limited mainly to antiseptic purposes.

The data presented make the development and implementation of new drugs from the 2,4-di-1H-hydroxyquinoline group in animal husbandry and veterinary medicine relevant scientific problem for veterinary pharmacology. These tools include, first of all, the new domestic drug Dioxidine, developed in the chemotherapy laboratory infectious diseases at the All-Russian Chemical-Pharmaceutical Institute (Moscow) and has high antimicrobial activity (A.V. Livshits, A.M. Marshak, G.A. Govorovich, 1976; E.N. Padeiskaya, 1978).

Purpose and objectives of the research. The main goal of this work is a pharmacotoxicological study of the domestic chemotherapeutic drug of the quinoxaline series - dioxidine with the aim of developing its use in animal husbandry.

To achieve this goal, the following tasks were set:

1. Find out the biological effect of the drug.

2. Determine the main pharmaco-toxicological properties of dioxidin, study its distribution in the body and its effect on the morphofunctional state of individual organs and tissues of animals, as well as the quality of animal slaughter products when prescribed.

3. To study the effect of dioxidin on digestion and, in particular, the motor-secretory functions of the stomach and intestines, and the absorption of energy substances.

4. To develop indications for the use of dioxidin and, in particular, to determine the growth-stimulating effect of the drug, its effect on the growth and development of farm animals, some metabolic indicators, as well as to establish therapeutic and prophylactic effectiveness for certain animal diseases and, in the prescribed manner, introduce them into animal husbandry practice and veterinary medicine.

The research was carried out according to assignment 0402 of the Russian Scientific and Technical Progress for Fundamental and Priority Research for 1992-1995. State No. registration 01.9.400075 88.

Scientific novelty. As a result of the research carried out using pharmacological, toxicological, physiological, microbiological and biochemical methods, the use of the domestic drug dioxidin, which is a derivative of quinoxaline, was experimentally studied and justified. In particular, its influence on the growth of animals, the main aspects of its metabolism, digestive processes, chemotherapy activity in relation to various microorganisms, fungi and helminths, absorption, distribution and excretion from the body, impact on the morphofunctional state were determined various organs and animal tissues.

In accordance with the requirements of the Veterinary Pharmabiocommission of the Veterinary Department of the Ministry of Agriculture of the Russian Federation, indications for use have been worked out and, in particular, in the treatment and prevention of diseases digestive tract and skin diseases.

Practical significance. A new domestic drug has been proposed for practical livestock farming, which has a pronounced growth-stimulating effect and high therapeutic and prophylactic effectiveness for gastrointestinal and skin diseases.

Practical significance is confirmed positive results extensive production tests and Temporary Instruction No. 13-5-2/1005 on the use of dioxidine, approved by the Veterinary Biocommission and duly approved by the Veterinary Department of the Ministry of Agriculture of the Russian Federation on July 10, 1997.

Implementation of research results. Industrial production dioxidine substance was mastered by the pharmaceutical enterprise "October" (St. Petersburg), and dosage form- Kaluga plant of veterinary preparations and Armavir biofactory.

In the conditions of livestock farms in different regions of the country, incl. in the Voronezh region and Krasnodar region, its use as a highly effective medicine is ensured.

Approbation of work. The dissertation materials were reported:

1. At meetings of the Academic Council at VNIVIPFiT on the results of research work for 1991-1994.

3. At the All-Russian Scientific and Industrial Conference "State and Development Prospects scientific research on the prevention and treatment of diseases of farm animals and birds”, dedicated to the 50th anniversary of the Krasnodar Scientific Research VS (Krasnodar, June, 1996).

Main provisions submitted for defense:

Results of a pharmaco-toxicological study of a new domestic quinoxaline drug - dioxidine;

Results of studying the biological effects of dioxidin;

The results of the practical use of the drug as a growth-stimulating agent and in the treatment and prevention of various animal diseases.

Publication of research results. The main content of the work is presented in scientific publications.

2. LITERATURE REVIEW

1. Dioxidin 1,4-di-N-oxide 2,3 bis-hydroxymethylquinoxaline is a new quinoxaline-type chemotherapeutic drug, promising for use in animal husbandry and veterinary medicine.

2. Dioxidin has high broad-spectrum antimicrobial activity, both in vitro and in vivo. Dioxidin exhibits the highest activity against gram-negative microorganisms. Coccal forms are more resistant to it (from 100 to 1000 μg/ml). Pasteurella was the most sensitive to the drug (3.12-12.5 μg/ml).

Dioxidin exhibits a pronounced chemotherapeutic effect in experimental Escherichia infection, and the dose of the drug significantly depended on the method of its administration.

3. The drug does not have acaricidal or ovicidal effects against psoroptes mites, or larvicidal against fly larvae.

A weak anthelmintic effect of the drug on roundworms of chickens and earthworms has been established.

The drug exhibits weak fungiostatic activity (0.050.1%) against dermatophyte fungi and some pathogens of animal mycotoxicosis. It has no effect on candida.

4. Dioxidin is a low-toxic drug for laboratory and farm animals. The LD50 of the drug for white mice when administered internally for different age groups varied from 1031.5 to 1212.5 mg/kg; for white rats when administered subcutaneously, this dose is 815.7; for piglets when administered orally - 1350 mg/kg.

With long-term repeated administration of dioxidine in optimal and threefold therapeutic doses, it does not have a toxic effect on the animal’s body, their digestion and urination processes, liver function, morpho-functional changes in other organs and tissues, as well as physicochemical characteristics and taste qualities of meat, does not exhibit locally irritating and skin-resorptive toxic effects.

The drug exhibits moderate cumulative activity.

5. The pharmacokinetics of the drug is characterized by absorption from the digestive canal and subsequent distribution in organs and tissues.

Complete elimination of the drug occurs within 72 to 96 hours. The recommended period for slaughtering animals for meat after the administration of dioxidine is 5-6 days.

6. The pharmacodynamics of the drug is due to pronounced antimicrobial activity against pathogens of many animal diseases, as well as versatile pharmacological action, expressed in an anti-inflammatory effect, a positive effect on certain aspects of protein, fat metabolism substances and digestive processes in animals. Multiple administration Dioxidin helps reduce the concentration of hydrogen ions in gastric juice. Stopping the drug helps restore its reaction to its original level within 24 hours. The administration of dioxidine is also accompanied by an increase in free and bound of hydrochloric acid, as well as the general acidity of gastric juice. The dynamics of amylase and trypsin activity are characterized initially by a decrease and then by an increase. The drug has a direct effect on the processes of glucose absorption in the small intestine. The maximum accumulation of glucose is observed when using therapeutic doses; large doses reduce the intensity of its absorption.

7. Dioxidin exhibits a high growth-stimulating effect on animals, which is accompanied positive influence for erythro- and hematopoiesis, level total protein. At the same time, animals have a greater yield of all categories of meat and bone tissue, the mass of internal organs increases, the protein-quality indicator of meat improves, the water content in meat decreases, and the fat and protein content increases.

In accordance with the materials of these studies, Temporary Guidelines for the use of dioxidine in veterinary medicine No. 13-5-2/1005 dated July 10, 1997 were developed. Industrial production of dioxidine has been mastered at the chemical and pharmaceutical association "October" (St. Petersburg), and the production of the dosage form at the Kaluga Veterinary Drugs Plant and the Armavir Biofactory.

PROPOSAL TO PRODUCTION

The use of the drug is regulated by the duly approved Temporary Guidelines for the use of dioxidine in veterinary medicine No. 13-5-2/1005 dated July 10, 1997.

5. CONCLUSION

The severity of the food problem in our country and the associated food security is largely due to the low productivity of farm animals.

One of the main reasons for this is inadequate feeding of animals, which does not ensure the normal course of biochemical processes in the organs and tissues of the body (I.V. Petrukhin, 1989; N.I. Kleimanov, 1987; V.T. Samokhin, 1981).

This situation is aggravated by industrial livestock farming technologies, which, due to the severance of connections with natural biotopes and physical inactivity, contribute to a decrease in the digestibility of biologically active substances (V.M. Danilevsky, 1980).

Therefore, in countries with intensive livestock farming, they widely use pharmacological correction physiological processes of the body using various biologically active substances, which allow accelerating the growth of both satisfactory and poorly developing animals. These drugs are called growth-stimulating agents, since they activate the functional activity of the body and its systems, mobilize its reserve capabilities and thereby accelerate the growth and fattening of animals (I.E. Mozgov, 1964, P.E. Radkevich, 1970) .

Along with antibiotics widely used for these purposes, in recent years antimicrobial compounds of the quinoxaline series have become widely used in the world and, in particular, the Bayonox drug from Bayer, the active ingredient of which is olaquindox triturate (D. Schneider et.al., 1976; ANON "Bayonox", 1978).

In our country, the All-Union Scientific Research Chemical-Pharmaceutical Institute has developed two new promising quinoxaline derivatives, dioxidine and quinoxidine, which have found quite wide application in medicine and are produced at the Oktyabr pharmaceutical association (St. Petersburg).

These drugs have versatile pharmacological effects, are low-toxic and therefore promising for use in animal husbandry and veterinary medicine.

All of the above served as the basis for a pharmacotoxicological study of the drug dioxidin with the aim of developing its use in animal husbandry and veterinary medicine.

Studies have established that dioxidin has versatile biological activity and, in particular, a high anti-H microbial effect against many microorganisms. Relatively higher activity of the drug was observed against gram-negative bacteria. Of these microorganisms, Pasteurella was the most sensitive to the drug. The minimum bacteriostatic concentration of the drug was 0.39-3.12 μg/ml, and the minimum bactericidal concentration was 0.78-6.25 μg/ml. Aerococcus viridans showed approximately similar sensitivity, which was 1.56-3.12 μg/ml in both cases. The drug showed a somewhat less antimicrobial effect against Pseudomonas aeruginosa, which nevertheless turned out to be quite high and amounted to: bacteriostatic at a concentration of 3×12-12.5 ml and bactericidal - 6.25-25.0 µg/ml. Salmonella and micrococcus turned out to be approximately equal in their sensitivity to the drug. At the same time, the minimum bacteriostatic concentration for both microorganisms was 12.5-25.0 μg/ml. Other Salmonella serotypes were more resistant to dioxidin. At the same time, the bacteriostatic and bactericidal activities of Salmonella dublin were 25-50 μg/ml, and Salmonella cholerae suis 50.0-200 μg/ml.

The antimicrobial effect of the drug on Bordetella also turned out to be quite pronounced and amounted to 25-100 μg/ml.

Various serotypes coli were approximately similarly sensitive to dioxidine. Moreover, their sensitivity manifested itself in concentrations from 12.5 to 100 μg/ml. The most resistant of the studied strains of microorganisms were gram-positive and, in particular, staphylococci and streptococci, the sensitivity of which varied from 100 to 400 μg/ml.

The activity of dioxidin against Proteus vulgaris was relatively low. Its bacteriostatic effect was at a concentration of 200-100 μg/ml, and its bactericidal effect was 100 μg per 1 ml of medium. Klebsiella was more sensitive to the drug, the effect of which was manifested at a concentration of 25-50 μg/ml.

Dioxidin also showed a pronounced chemotherapeutic effect in experimental Escherichia infection.

Moreover, its dose depended on the route of administration. Thus, when administered intraperitoneally on the 15th day of the experiment, 100% survival of white mice was noted at a dose of 10 mg/kg. ED50 in this case was 2.5 mg/kg, but when dioxidine was administered orally, the ED50 parameters were higher and reached 61.5 mg/kg.

Dioxidin, administered an hour after infection of the animal, protected white mice from death at a dose of 10 mg/kg, the ED50 being equal to 4.1 mg/kg. The administration of dioxidine 3 hours after infection increased the unit and amounted to 7 mg/kg.

Tests have shown that a 1% solution of dioxidine does not have an acaricidal effect against ticks. psoroptes, since no significant changes in the condition of the mites and their death were noted. A similar result was obtained in the control.

However, no ioacidal effect of the drug was observed. The hatching of larvae in this case was similar to the control.

Dioxidin did not have a larvicidal effect on fly larvae. The hatching of larvae did not change significantly, but after 2-3 days they pupated.

When studying anthelmintic action The drug has a weak destructive effect on earthworms. Moreover, their death occurred within 90 minutes. The picture of intoxication was characterized by weak excitation of the worms, followed by paralysis and death.

The death of chicken roundworms occurred after a 10-hour exposure.

It has been established that dioxidin exhibits weak fungiostatic activity (^.05-0.1%) against dermatophyte fungi. In relation to the causative agents of mycotoxicosis (Fusarium), the drug showed a destructive effect at a concentration of 40 mg/kg, and the effect on Stachybotris alternans was manifested at a concentration of 0.5 mg/kg. Dioxidine had no effect on Candida.

Thus, dioxidin has a weak antifungal and anthelminthic effect.

A study of the main toxicological parameters of dioxidine showed that it is a low-toxic drug. Its maximum tolerated dose for white mice when used internally, depending on age, ranges from 600-1000 mg/kg. LD50 varied from 1031.5 to 1212.5 mg/kg. A dose of 1400 mg/kg caused the death of all mice.

For white rats with subcutaneous administration of the drug, these parameters were respectively 600; 815.7 and 1000 mg/kg.

Piglets turned out to be less sensitive to dioxidine compared to laboratory animals. At the same time, the MTD was 1200; LD50 -1350 and LDuo - 1700 mg/kg.

Clinical picture intoxication was characterized by depression, decreased pain sensitivity, lack of appetite, coma. Convulsions and impaired coordination of movement were recorded in piglets. Dioxidine, when administered internally for a long time at 50 times the therapeutic dose, caused death within 6-10 days. When administered at a 20-fold dose, the death of animals was 60%, which indicates the low toxicity of the drug.

In similar experiments conducted on sheep, it was established that dioxydine, when administered internally in 10 times therapeutic doses, did not cause signs of intoxication and death of the animals. 20 times therapeutic dose caused the death of all animals within 5-10 days. Blood tests did not reveal any pronounced changes in blood parameters.

With long-term internal administration (21 days) at a 3-fold therapeutic dose, the drug did not have a pronounced toxic effect on the clinical status of animals, blood parameters and the weight of internal organs. At the same time, the temperature, pulse, and respiration parameters of the rabbits did not undergo significant changes throughout the experiments (15 days).

It did not have a local irritant or skin-resorptive toxic effect during skin applications and conjunctival tests.

Dioxidin did not cause disturbances in the basic functions of the liver, as well as in the processes of digestion and urination.

It showed moderate cumulative activity. The cumulation index was 6.1; 3.7; 1.8%, respectively, after 24, 48 and 72 hours. The drug reversibility index during these time intervals reached 93.9; 96.3;98.2% respectively.

Histological examination of the internal organs of animals that received three times therapeutic doses of dioxidine for a long time did not reveal morphological changes in the liver, kidneys, or heart. Only in some animals were weakly focal injections of capillaries in the kidneys noted, as well as weak catarrh mucous membrane of the stomach and jejunum.

The conducted veterinary and sanitary examination of pig slaughter products shows that the carcasses of the experimental (received dioxidine) and control animals did not differ in external characteristics, and no visible changes in their internal organs and tissues were also detected.

Dioxidin does not change the taste of meat, as evidenced by its commission tasting assessment and biochemical research meat from pigs treated with the drug.

The pharmacokinetic parameters of dioxidin are characterized by its absorption and distribution in organs and tissues. Both with a single and five-time internal application to pigs at a dose of 10 mg/kg for 10 days, the drug is registered in the body only in the form of traces and not in all organs. Moreover, its traces were noted 6 hours after administration only in the kidneys, liver and spleen. After 48 hours, dioxidine was not detected in any of the examined organs.

When the drug is administered intramuscularly at a dose of 1 ml per 1 kg of body weight in the form of a 1% solution, its residual quantities are detected after 48 hours in samples of blood, liver, kidneys, lungs and skeletal muscles. After 72 hours, its content decreases sharply, and after 96 hours it is not detected.

Thus, complete elimination of the drug occurs within 7296 hours, so the recommended period for slaughtering animals for meat after treatment with dioxidine is 5-6 days.

Studies of certain aspects of pharmacodynamics have established that dioxidin, in addition to its pronounced antimicrobial action has a diverse effect on the functions of the digestive canal.

Thus, when the drug is diluted in concentrations of 1:1000 and 1:500, a slowdown in the rhythm and amplitude of contractions of isolated sections of the intestine is recorded, which are restored with subsequent lavage.

At the same time, five-time internal administration of dioxidine to rabbits at a dose of 30 mg/kg increased the motor function of the stomach, which manifested itself in the form of an increase in its bioelectrical activity.

Repeated administration of dioxidine contributed to a decrease in the concentration of hydrogen ions in gastric juice. Discontinuation of the drug led to the restoration of his reaction to the original within 24 hours. At the same time, this was accompanied by an increase in the concentration of free and bound hydrochloric acid, as well as the general acidity of the juice, and an increase in the pH of intestinal juice, which after 3-fold administration was 20.7% higher than the background values. The dynamics of intestinal juice amylase activity was characterized by a decrease at the beginning, and then by an increase of 3-13%. A similar picture was recorded for trypsin activity.

When studying parietal digestion of dioxidine for the absorption of energy substances, it was shown that the drug has a direct effect on the structural elements of the intestinal mucosa. The result of this action is an increase in the intensity of absorption and accumulation of glucose by the tissue of the isolated area, however, different doses of the drug affect these processes differently. The maximum accumulation of glucose by tissue is observed when therapeutic doses are used, and large doses somewhat reduce the intensity of its absorption.

It was found that dioxidin at a dose of 10 mg/kg leads to an increase in glucose content in the distal part of the intestine when incubated for 30 and 60 minutes in the first experimental group compared to the control; its amount was respectively: 0.6±0.02 mM and 0.1±0.06; 0.6±0.07 and 0.2±0.07 mM.

Dioxidin at a dose of 30 mg/kg caused a sharp increase in the accumulation of glucose in the intestinal mucosa. The glucose concentration in this case in the distal area after 30 minutes of incubation here reached 1.1 ± 0.02 mM, whereas the control value was 0.1 ± 0.04 mM. With increasing incubation time (60 minutes), the increase in concentration was observed to a lesser extent.

In the proximal part of the intestine, the accumulation of glucose was not so intense. Thus, after 30 minutes of incubation its level was 0.7±0.02 mM - 0.8±0.1 mM, while baseline was 0.2±0.07 mM. After a 60-minute incubation, the amount of accumulated glucose in this part of the intestine increased slightly compared to the control. There was a general trend toward an increase in glucose concentration in both the proximal and distal parts of the intestine after a 30-minute incubation compared with that after a 60-minute exposure.

With direct contact of the drug with microvilli of the intestinal mucosa, the intensity of glucose absorption by the jejunum of rats increased with the addition of dioxidine to the incubation medium.

Dioxidin added to the incubation medium at a concentration of 10 mg/l caused an increase in the accumulation of glucose in the jejunum tissue. Thus, the initial glucose concentration was 0.1±0.07 mM. After 30 minutes of incubation, the concentration of accumulated glucose increased to 0.4 ± 0.1 mM and 0.5 ± 0.1 mM in the proximal and distal sections, respectively. After 60 minutes of incubation, there was a further increase in glucose accumulation, especially in the distal region. Here its level reached 0.8±0.1 mM, while in the proximal section it increased slightly - to 0.5±0.08 mM.

At a concentration of 15 mg/l of solution, dioxidin had the greatest increase in glucose accumulation. Its initial content was 0.15±0.08 mM. After 30 minutes of incubation, the glucose level reached 0.6±0.09 mM in the proximal region. The glucose concentration in the distal region after 30 minutes of incubation was even higher: 1.1 ± 0.09 mM. There was further accumulation of glucose in the intestinal segments after 60 minutes of incubation, especially in the distal section compared to the proximal one: 1.6 ± 0.08 mM and 1.3 ± 0.08 mM, respectively.

Dioxidin at concentrations of 30 and 40 mg/g caused a slight accumulation of glucose in the intestinal mucosa.

Thus, dioxidin at a dose of 15 mg/kg, administered with food to beo and lye rats for 7 days, does not affect the absorption of glucose from the mucous membranes. small intestine. At a dose of 30 mg/kg body weight, the drug increases the accumulation of glucose in the intestine, especially in its distal area after 30 minutes of incubation. When the drug was added directly to the incubation medium, the greatest increase in glucose concentration occurred with the drug at a dose of 15 and 50 mg/l.

If the intestines of such rats, placed in an incubation medium without the drug, are only capable of accumulating glucose 1.5 times more compared to its initial level, then with the addition of dioxidine, the intensity of absorption increases 4-5 times. The maximum concentration of accumulated glucose in the intestine incubated without dioxidine is 0.44 ± 0.02 mM, with dioxidine - 0.65 ± 0.03 mM.

Consequently, the drug has a direct effect on the structural elements of the intestinal mucosa. The result of this action is an increase in the intensity of absorption and accumulation of glucose by the tissue of the isolated area.

In conditions of unbalanced nutrition, the effect of the drug is less effective. 0

With balanced feeding, the animals gained body weight 2 times faster than the controls, and the amount of food consumed did not increase.

Analysis of glucose absorption by the jejunum showed that the intensity of this process in experimental animals is 3-4 times higher. These facts can be considered as one of the mechanisms that ensure the action of dioxidin as a growth stimulator in animals.

A study of biochemical blood parameters revealed high activity of dioxidin, which is characterized by increased energy and protein metabolism in animals. At the same time, an increase in the content of total protein, RNA, as well as the albumin fraction of blood serum is recorded, which indicates the activation of protein metabolism. A decrease in urea indicates a more rational course of these processes and better utilization of proteins by the body.

However, the results of these experiments also indicate an increase energy metabolism both carbohydrate and fat, in particular, their more optimal flow, and, consequently, better energy supply for the biochemical processes occurring in the body. Ultimately, all this contributed to a greater increase in body weight in the experimental animals.

When conducting clinical trials of dioxidin in order to develop indications for its use, it was found that the pronounced chemotherapeutic properties and versatile pharmacological action contribute to the high therapeutic and prophylactic effectiveness of the drug in various diseases animals, as well as to stimulate their growth. Dioxidin showed a high growth-stimulating effect on pigs, amounting to 149.9% of the control in the first series, 149.9% in the second, and 129.6% in the third. It was noted that the animals ate the food containing the drug well and no toxic effects on their bodies were detected. The effect on the blood is marked by a positive effect on the content of red blood cells and their saturation with hemoglobin, an increase in the level of total protein; in experimental pigs there is a greater yield of all categories of meat, as well as bone tissue. When large doses of the drug are prescribed, a decrease in the yield of fatty meat and an increase in the amount of lean meat is recorded. Characteristic is an increase in the content of tryptophan and hydroxy-proline and, as a result, an improvement in the protein-quality indicator of meat. The water content in meat decreases, and the fat and protein content increases. In parallel, animals show an increase in the mass of internal organs (liver, kidneys, heart). After the cessation of the drug's effect, the mass of these organs is mainly restored.

At clinical trials 5% dioxidine ointment for dog dermatitis, it has been established that the drug, when administered in the form of cutaneous applications 2 and 4 times with an interval of 2 days, exhibits a pronounced healing effect with this disease. After one or two uses of the drug, necrotic scabs were rejected from the affected areas, the skin became elastic, moist and painless, and hair growth began on days 6 and 15. The areas were completely overgrown with hair and the healing process began within 12-30 days. The use of dioxidine in the wound process contributed to earlier epithelization and granulation of the wound surface, acceleration and resorption of inflammatory edema and a decrease in the purulent-exudative process. The pain of the wounds decreased, and the general condition of the animals improved. The experimental animals recovered 2-3 days faster than the control animals. The effectiveness of the drug for skin diseases is due to its ability to resolve inflammatory swelling, stimulate regenerative processes, dilate blood vessels at the site of application and increase their permeability, which is due to its anti-inflammatory, emollient, and improving skin trophism effect.

When studying the therapeutic and prophylactic effectiveness of diarrheal diseases in piglets, it was shown that the administration of dioxidine contributed to a rapid improvement general condition, restoration of gastrointestinal tract functions and disappearance clinical signs diseases within 2-4 days of treatment. The therapeutic effectiveness of the drug ranged from 80-100./

Prescription of the drug with for preventive purposes contributed to a significant improvement in their general condition and appetite. As a result, the preventive effectiveness of dioxidin was 95%

At the same time, the drug did not have a pronounced toxic effect on the morphobiochemical parameters of pig blood and did not exhibit other side effects.

The materials of these studies of the pharmacological and toxicological properties of dioxidine, its effectiveness in various diseases, the developed regulatory and technical documentation for its use were approved by the Veterinary Biocommission of the Department of Veterinary Medicine of the Ministry of Agriculture and the Russian Federation, which served as the basis for approval in the prescribed manner of the Temporary Guidelines for the use of dioxidine in Veterinary Medicine 13- 52/1005 dated 07/10/97.

Industrial production of dioxidine was mastered at the chemical and pharmaceutical association "October" (St. Petersburg), and the production of the dosage form was mastered at the Kaluga Veterinary Drugs Plant and the Armavir Biofactory. Currently, dioxidin is being widely introduced into veterinary practice in accordance with the approved instructions.

Thus, the new quinoxaline drug dioxidin is low toxic medicine, which has pronounced pharmacological and chemotherapeutic activity. It is effective as a therapeutic and prophylactic agent for diseases of the skin, digestive and respiratory canals, for obstetric and gynecological diseases, and also as a growth-stimulating agent.