Roncoleukin: Guidelines for Veterinarians

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Roncoleukin^®: Guidelines for Veterinarians

A.N. Moiseev, E.D. Sakharova

LTD "Biotech" Russia, 197198, Saint-Petersburg, Bolshaya Pushkarskaya, 20, 5-312
Phone: +7(812)346-60-53, +7(905)212-99-99
E-mail: vet@biotech.spb.ru

The guidelines represent the results of numerous researches connected with usage of Roncoleukin^® (recombinant interleukin-2) as a preventive and therapy means against various deceases of animals. The researches are performed in the scientific institutes, veterinary clinics and agricultural enterprises of Russia, Byelorussia, Ukraine and Kazakhstan. The special attention was paid to the characteristic of interleukin-2, the researches supported feasibility of its usage as an immunocorrector, and demonstrated methods and peculiarities of its usage, as well as schemes of preventive measures and therapy against infectious, oncologic and other diseases of animals.

The recommendations are intended for veterinarians and medical assistants, as well as for students of veterinary higher educational institutions.

Content

Part 1. General Questions

Cytokines
Roncoleukin^® - Recombinant Interleukin-2 of Human Being
Prerequisites to Usage of Roncoleukin^® in the Veterinary
Possibilities of Roncoleukin^® in the Veterinary Science
Form of Issue
Storage Conditions
Compatibility with Other Preparations
Methods of Intake

Part 2. Schemes of Roncoleukin^® usage

Medication of Small Domestic Animals
Medication of Horses
Medication of Cattle
Medication of Small Cattle
Medication of Swine
Medication of Fur Animals and Rodents
Medication of Farming Birds
Medication of Wild and Exotic Animals
Medication of Fish

Part 1. GENERAL QUESTIONS

1. CYTOKINES

The family of cytokines includes interleukins, interferones, chemokines, growth factors and colony-stimulating factors representing signal polypeptide molecule of immune system. Obtaining a wide specter of biological activity, they define not only an adequate level of immune reaction, but regulate interactions of basic integrative systems of organism – nervous, immune and endocrinous systems.

The structure and mechanism of action of the majority of cytokines are characterized enough. Thanks to usage of gene engineering methods and modern biotechnology, many cytokines nowadays are produced in the form of recombinant preparations identical to endogenous molecules in the number which is enough for their clinical use.

Usage of recombinant cytokines, providing adequate and task-oriented medication correction of immune dysfunctions, increases effectiveness of immunotherapy and treatment as a whole. Cytokines introduced into the organism replenish the deficit of endogenous regulatory molecules and reproduce their effects in full. It is especially important in conditions of heavy or chronic pathology, when usage of traditional immunomodulator or inductors of cytokine synthesis is useless due to exhaustion of compensation abilities of the immune system.

At the present moment, the therapy by recombinant cytokines is one of the most perspective and constantly developing directions of the immunopharmacology.

2. RONCOLEUKIN^®— RECOMBINANT INTERLEUKIN-2 OF HUMAN BEING

The preparation is produced by biotechnological methods from cells of producer – recombinant strain of baker's yeasts Saccharomyces cerevisiae, whose genetic apparatus has an incorporated gene of human being interleukin-2. The active substation of Roncoleukin^®- the recombinant yeasty interleukin-2 of human being – is a polypeptide, consisting of 133 amino acids with the molecular weight of about 15.4 kilodaltons.

Interleukin-2 is one of the key components of immune response. Its deficit results in the exhaust of immune system, from transitory to total one.

The total immune deficiency, accompanying the heaviest pathology, cannot be corrected by traditional immunomodulator or inductors of cytokine synthesis due to exhaustion of compensatory possibilities of immune system.

Shortage control of interleukin-2 deficit by introducing Roncoleukin^® normalizes following processes:

recognition of antigens;
proliferation and differentiation of immunocompetent cells;
production of cytokines by cells (including interferones);
cytolytic activity of monocytic cells, natural and specific killers;
functional activity of granulocytes;
production of antisubstances.

Roncoleukin^® - is a structural and functional analogue of endogenous interleukine-2. It has an expressed immune-resolved activity directed on strengthening and optimization of antibacterial, antiviral, and antifungal immunity.

Roncoleukin^® - is the main stimulant for formation of such important components of such autogenous immunity as lymphokine-activated killers and tumor swelling infiltrative cells.

Roncoleukin^® activates processes of reparation and regeneration of tissues.

In cases of heavy system pathology with manifestations of total immunodeficiency Roncoleukin^® is the measure of immune rehabilitation.

Spectrum of Interleikine-2 (IL-2) Regulatory Effects

Activation of NK-cells, stimulation of differentiation

Autocrine action

Stimulation of proliferation of cytolytic and secretory activity of T-lymphocytes

Activation of B-lymphocytes, stimulation of their proliferation

Activation of antigen-presenting cells

3. PREREQUISITES TO USAGE OF RONCOLEUKIN^® IN THE VETERINARY

The comparative study of animal immune system demonstrated that it is among the most conservative systems of organism. The high level of homology, its organization and functioning is specific for various representatives of hot-blooded organisms. In particular, the comparative analysis of amino acid sequence of interleukin-2 demonstrated a significant similarity of its structure for various mammals and a human being. The index of homology for dogs is up to 84%, for cats is up to 80%. The functional similarity was demonstrated in the researches in vitro: interleukin-2 of human being stimulates the proliferation of T-lymphocytes of dogs and cats. In addition, experimental works proved effectiveness of treatment using recombinant interleukin-2 for domestic and farm animals, birds and fish affected by oncological, bacterial and virus diseases. For example, introduction of human being's recombinant interleukin-2 to dogs with osteosarcomas including in cases of metastasis in the lungs and other organs results in remission for the period from eight months to two years.

The stated facts created prerequisites for usage of Roncoleukin^® in the veterinary science at the same areas as in the medicine.

4. POSSIBILITIES OF RONCOLEUKIN^® IN THE VETERINARY SCIENCE

It is recommended to use Roncoleukin^® in the veterinary practice for curing mammals (pets, horses, cattle, small cattle, swine, rodents and others), birds, reptilians and fish.

Roncoleukin^® is used in the form of mono-therapy or as a component of complex therapy for animals of various diseases and conditions:

Pyoinflammatory diseases

sepsis,
burns and freezing injuries,
peritonitis,
pancreatitis,
apostems and phlegmons,
endometritis,
staphylococcal damages,
traumatic states.

Infection diseases:

viral (plague of carnivorous, viral hepatitis, parvovirus enteritis "olympiyka"), SARS of cats, infectious rhinotracheitis, virus diarrhea, respiratory syncytial infection, parainfluenza-3 and etc.),
bacterial (necrosis germ, leptospirosis, clamidiosis, colibacillosis, salmonellosis, pasteurellosis, erysipelas, and etc.),
fungal,
mycoplasmosis.

Skin diseases:

atopic dermatitis,
dermatitis of specific origin,
chronic recidivating tetters,
microsporia, trichophytia, head scald("trichophytosis"),
demodicidosis.

Diseases of eyes:

keratitis,
iridocyclitis,
raumatic damages of eyes.

Diseases of mouth cavity:

stomatitis,
diseases of dentogingival pockets,
viral papillomatosis,
osteomyelitis of jaw bones.

Respiratory diseases:

rhinitis,
sinusitis,
bronchitis.

Diseases of the digestive tract:

dyspepsia,
viral and bacterial ethiology.

Hereditary diseases:

cystic disease of nephros.

Stress;

transportation,
various manipulations.

Surgery:

prophylactic introduction in cases of risks connected with suppurative complications,
preparation for planned operations.

Oncology:

prevention of post-operation aphylaxis,
usage at the background of X-ray therapy, chemotherapy and hormonotherapy,
immunotherapy of cancers,
prevention of metastasis appearance during the post-operation period;

Adjuvant vaccine;

Violation of mineral metabolism;

Parasitology:

for increasing immunobiological reactivity of organism

Geriatrics.

5. FORM OF ISSUE

Roncoleukin^® is produced in liquid form. It is filled in ampoules with the volume of 1 ml and flacons of 10 ml. The ampoule contains recombinant interleukin-2, as follows: 0.05 mg (50 000 МЕ), 0.1 mg (100 000 МЕ), 0.25 mg (250 000 МЕ) and 0.5 mg (500 000 МЕ). The flacon contains recombinant interleukin-2, as follows: 1 mg (1 000 000 МЕ), 2 mg (2 000 000 МЕ), 5 mg (5 000 000 МЕ) and 10 mg (10 000 000 ME). There are three ampoules in the pack, flacons are packed separately. The ampoules have a blue marker band. Any other packaging and filling are permitted.

6. STORAGE CONDITIONS

It is recommended to store Roncoleukin^® at the temperature from +2 to +10 °С.
When the conditions of storage are observed, the preparation keeps effectiveness within two years from the moment of preparation. It is permitted to transport it at room temperature within the period of two weeks. The solution prepared for injections do not lose its activity at the temperature from +4 to +10 °С within 72 hours.

7. COMPATIBILITY WITH OTHER PREPARATIONS

Roncoleukin^® is compatible with a majority of other pharmaceuticals, but it is necessary to observe the following rules when using it:

it is undesirable to introduce Roncoleukin^® with any other preparations and vaccines in one syringe (except vaccination of birds);
do not introduce Roncoleukin^® in the solutions which include glucose, since the level of preparation activity decreases;
t is not recommended to use Roncoleukin^® simultaneously with corticosteroid preparations of local and system purpose.

8. METHODS OF INTAKE

Subcutaneously: mix the content of ampoules (flacons) in 2 - 5 ml 0.9 % of the sodium chloride solution or water for injections (in case of sickliness of 0.9 % sodium chloride solution introduction).
Intravenously: the content of ampoule with Roncoleukin^® transfer to 100 - 400 ml of 0.9 % sodium chloride solution for injections. Inject slowly in drips (!)
Sublingually (under the tongue): mix the content of ampoules in 2 - 10 ml of 0.9 % sodium chloride solution or water for injections (depending on the size of animal) and place it under the tongue.
Intranasally: mix the content of ampoules in 4 ml 0.9 % of sodium chloride solution or water for injections and instill it in the nose of animals considering the weight of body:
- up to 5 kilograms – use the ampoule 100 000 ME,
- up to 20 kilograms – use the ampoule 250 000 ME,
- more than 20 kilograms – use the ampoule 500 000 ME,
- Instill two drops in each nostril not less than 3-5 times per day.

Aerosol (inhalant): mix the content of ampoule in the necessary quantity of 0.9 % sodium chloride solution or water for injections and spray it using the installation in the presence of animal. Perform inhalation in the warm premise.
External: mix the content of ampoule in 5 - 10 ml of 0,9 % sodium chloride solution or water for injections and use it in the form of applications or surface irrigation.
Intravesical: mix the content of ampoule 100 000 - 250 000 МЕ in 5 - 50 ml (depending on the size of animal ) of 0.9 % sodium chloride solution and inject it through the catheter.
Peroral: mix the content of ampoules in 2 - 10 ml of 0.9 % sodium chloride solution or water for injections (depending on the size of animal) and let the animal drink it.

ATTENTION! Do not shake the solution. Avoid foam formation.

Part 2. SCHEMES OF RONCOLEUKIN^® USAGE

9. Medication of pets

9.1. Oncological diseases
Roncoleukin^® is used in complex therapy of various oncological diseases:

melanoma,
epidermoid carcinoma,
clear-cell carcinoma,
osteoblastic sarcoma,
neoplasm in the mouth cavity,
tumoral pleuritis,
tumor of mammary gland,
lymphosarcoma,
colorectal cancer.

It is necessary to use Roncoleukin^® in combination with operative treatment to prevent metastasis and origination of secondary immune deficiency, resulting in origination of post-operation complications.

In addition, Roncoleukin^® should be used during and after chemotherapy and X-ray therapy.

The preparation is introduced intravenously or subcutaneously in quantity of 10 000 – 15 000 ME/ kg Course of treatment- up to 5 injections with intervals of 24 - 48 hours. In 30 days it is recommended to perform the repeated course of Ronkoleukin^®.

After the course of treatment we may observe:

localization of neoplastic process,
termination or weakening of inflammatory process,
disappearance of hydrops and occlusion of cracks,
stabilization of hematological exponents,
recession of level of sialic acids,
significant improvement of systemic condition.

ATTENTION! In cases of cancerous diseases of blood and lymph, use Roncoleukin^®with care.

9.2. Post-operation conditions Post-operation complications

During the post-operation period it is recommended to use from 1 to 3 injections of preparations with a dose of 5 000 - 10 000 МЕ/kg with an interval of 24 hours.

Usage of Roncoleukin^® provides:

decrease of possibilities of post-operation complications,
if post-operation complications exist – intensive regeneration of tissues, significant improvement of systematic conditions of animals,
reduction of recovery terms.

9.3. Contaminated surgery

The recommended course of treatment is 2 - 3 injections with the dose of 10 000 МЕ/kg with the interval of 24 - 48 hours.

After the course of treatment we may observe:

stabilization of systemic condition (appearance of appetite, normalization of temperature),
absence of post-operation complications,
normalization of blood sedimentation rate, blood-picture, level of kreatinine in the serum on 5th day after operation,
quick repair of wounds,
reduction of recovery terms.

9.4. Infectious and Destructive Processes in the Bony Tissue

Roncoleukin^® is used for complex therapy of infection and destructive processes in the bony tissues, as follows: 2 - 3 injections in the quantity of 10 000 ME/kg with the interval of 24 - 48 hours. If the animal is in grave condition, this course of treatment must be repeated in 30 days.

After the course of treatment we may observe:

improvement of systemic condition of animals,
decrease of puffiness and lameness,
decrease of local hyperthermia,
decrease of dermatic crack,
reduction of recovery terms.

9.5. Pyometra, Hemometer (Nonoperative Treatment)

In some cases (for old and weaken she-dogs, if the risk of lethal outcome during the operation exists), it is possible to use Roncoleukin^® as part of complex therapy for acute endometritis.

The preparation is introduced with the dose of 10 000 ME/kg once, intravenously, in drops, then subcutaneously with the same dose – 3 injections with the interval of 48 hours against the background of remedies supporting cordial activity, spasmolytics and gynecological grass decoctions.

At that, we may observe:

termination of pyogenic (bloody issues) on the 3 - 5th day from the beginning of therapy,
decrease of temperature to the physiological standard at the 2nd day,
resorption of exudation and involution of alvus at the 7 - 14th day of complex therapy.

Introduction of preparation should be continued on a monthly basis, subcutaneously, with the dose of 10000 ME/kg repeatedly with the interval of 48 hours in order to prevent recidivation of disease.

9.6. Infection Diseases (Bacterial, Fungal and Viral)

In cases of acute diseases, it is recommended to use the preparation with the dose of 5 000 - 10 000 ME/kg, in cases of chronic diseases – with the dose of 10 000 - 15 000 МЕ/kg. The interval between introductions is 24 - 48 hours. In the course of complex therapy of infection diseases it is necessary to use 2 - 3 injections of Roncoleukin^®, when curing heavy diseases – up to 5 injections.

If the preparation is included in the complex therapy of acute diseases we may observe:

quick normalization of blood biochemical measurements,
reduction of recovery terms.

If the preparation is included in the complex therapy of chronic diseases we may observe:

clinical recovery of animals,
normalization of antibody titers.

In addition, there is a possibility to perform vaccination of animals.

9.7. Adjuvant Vaccine

It is recommended to use Roncoleukin^® simultaneously with vaccination, but using different syringes, subcutaneously, with the dose of 5000 МЕ/kg, once.

As a result:

the immune reaction of organism on introduction of vaccine is increasing - antibody titers in the serum of blood of animals, which were treated with Roncoleukin^® and the vaccine, are 1.5 - 3 times higher in comparison with animals, which were vaccinated without usage of Roncoleukin^®.
the possibility of successful vaccination is increased – the immune reaction to introduction of vaccine together with Roncoleukin^® is observed for 100 % of animals.

9.8. Skin Diseases

It is recommended to use the preparation in the course of complex therapy, 2 - 5 injections with the dose of 5000-10000 ME/kg with the interval of 24 - 48 hours. In case of chronic disease and very heavy cases, it is preferably to repeat the course in 40 days from the moment of last injection.

After the course of treatment we may observe:

reduction of recovery terms,
absence of repeated bouts.

9.9. Diseases of Eyes

It is recommended to use the preparation in the course of complex therapy, 2 - 3 injections with the dose of 10 000 ME/kg with the interval of 48 hours. In case of chronic disease it is recommended to repeat the course of therapy in three weeks from the moment of last injection. The subconlunctival introduction of this preparation is possible.

9.10. Diseases of Mouth Cavity

In case of viral papillomatosis in the mouth cavity of dogs it is recommended to introduce Roncoleukin^® using injections under the base of papilloma at the 1, 3, 5, 7 and 9th day with the dose of 10 000 ME/kg of body weight. After receiving the overall volume of preparation, it is necessary to distribute injections on all papillomas without exceptions. The insulinic syringe is used for convenience of Roncoleukin^® usage. Absolute recovery of dogs occurs in 11 days.

Curing stomatitis, it is recommended to introduce Roncoleukin^® in the submucosal into the inflammatory tissue, or apply it on the mucous membrane, right on the inflammatory tissue. First clinical signs of recovery are observed every other day, after the beginning of cure, the final recovery of animals is registered in 3 - 7 days.

When curing dentogingival pockets it is recommended to introduce Roncoleukin^® into the submucous membrane of flexible part of gingival, or using pincers pull the edge of dentogingival pocket and using a pipette instill 2 - 4 drops depending on the depth and size of pocket. Full recovery (healing of dentogingival pockets) occurs in 7 - 9 days.

In the course of treatment of osteomyelitis in the bones of jaw, it is recommended to use Roncoleukin^® subcutaneously, 2 - 3 injections with the interval 24 - 48 hours with the dose of 10 000 ME/kg. As a result, the period of treatment shortens in 2 times and decreases the number of repeated bouts.

9.11. Respiratory Diseases

It is recommended to use the preparation in the course of complex therapy, 2 - 3 injections with the dose of 10 000 ME/kg with the interval of 24 - 48 hours. In case of untimely beginning of treatment, the course of injections must be increased up to 5 injections. In cases of rhinitis, the preparation may be introduced intranasal.

9.12. Diseases of Excretory System

It is recommended to use the preparation in the course of complex therapy, 2 - 3 injections with the dose of 10 000 ME/kg with the interval of 24 hours. In case of untimely beginning of treatment, the course of injections must be increased up to 5 injections. In cases of cystitis, urolithiasis, the preparation may be introduced interstitially (intravesically).

In the course of complex therapy of virus-challenged chronic glomerulonephritis and chronic disease of nephros of cats, it is recommended to use Roncoleukin^® in two months intravenously or subcutaneously with the dose of 10 000 - 15 000 МЕ/kg, 5 injections with the interval of 24 - 48 hours. Animals are prescribed with low-protein diet.

Usage of Roncoleukin^® during complex treatment virus-challenged chronic glomerulonephritis and chronic disease of nephros grades immunosuppression action of pathogenetic preparations (steroid hormones), increases length of remission between repeated bouts, it promotes to reduction of chronic kidney failure and improves the priognosis of disease.

9.13. Hereditary Diseases

In cases of cystic disease of cats, it is recommended to use Roncoleukin^® within the process of complex therapy, 5 injections with the dose of 20 000 ME/kg with the interval of 48 hours. It is necessary to repeat the course of treatment in 30 days after the last injection.

After the course of treatment we may observe:

improvement of quality of life of the animal (appearance of appetite, normalization of behavioral reactions, removal of pain syndrome),
decrease of risk of other diseases appearance, connected with immunodepression state of the animal.

9.14. Hypothermal Syndrome of Cats

It is recommended to use Roncoleukin^® in combination with generally accepted measures. The preparation should be injected subcutaneously with the dose of 10 000 - 15 000 МЕ/kg of weight – up to 5 injections with the interval of 24 - 48 hours. The first injection to cats may be injected subcutaneously, then the necessary number may be drunk with water during the period of several days. These schemes provide a possibility to improve significantly the effect from reanimation measures.

9.15. Preventive Measures Against Adaptation Diseases

Roncoleukin^® is used as a measure for stress release during various manipulations, transportation and etc. It is recommended to use the dose of 5000 ME/kg one time, but not later than 48 hours before the beginning of proposed actions.

As a result:

the immune reaction of organism is increased,
animal easily undergoes various manipulations, transportation, and etc.

9.16. Preparation for Exhibitions and Competitions

It is recommended to use Roncoleukin^® to prepare animals for exhibitions and competitions. It is necessary to use the dose of 5 000 ME/kg two times, with the interval of 24 - 48 hours. The last injection should be executed not later than 48 hours before the proposed beginning of arrangements.

9.17. Immune Rehabilitation

Old and weak animals should be treated with Roncoleukin^® as a supporting therapy once per quarter one or two times with the interval of 48 - 72 hours with the dose of 5 000 - 10 000 ME/kg.

To improve the immunobiological reactivity of organism in case of parasitic diseases, it is recommended to use Roncoleukin^® subcutaneously or intravenously (!) with the dose of 5 000 ME/kg, one time.

9.18. Stimulation of Inborn Immunity

To stimulate inborn immunity especially of puppies and kittens with a weak sucking reflex, it is recommended to inject Roncoleukin^® subcutaneously or oral with the dose of 5 000 ME/kg one or two times with the interval of 24 hours.

10. Medication of Horses

Horses are treated by Roncoleukin^® subcutaneously or intravenously by drops (!) with the dose of 1000 ME/kg from the weight of body. In specific cases, it is possible to inject the preparation in the form of circular (short) blockade and external applications. It is also recommended to inject Roncoleukin^® sublingually, intranasally or oral in cases when there are difficulties with performing injections to the animal.

The hypodermic injection of Roncoleukin^® to horses may be accompanied by a short pain reaction ("burning") – up to 1 minute. In order to decrease this effect it is necessary to dilute the preparation, intended for injections, with water.

It is not recommended to inject Roncoleukin^® to horses shortly before or right after physical activities, as well as in hot weather due to the effect of hyperthermia.

Horses with heavy diseases of the conducting system and the heart valve set, Roncoleukin^® should be used with care.

The heart attack of horse is a contraindication for usage of Roncoleukin^®.

10.1. Traumatic Injuries, Burns and Freezing Injuries

In case of acute injuries, accompanied by failures of skin, walls and lower margins of hoof and soft tissues, Roncoleukin^® is injected subcutaneously, one time, with the dose of 1000 ME/kg, in order to prevent suppurative complications.

Roncoleukin^® is injected with the dose of 1000 - 2000 ME/kg, one time for curing infected wounds, apostems, fistulas, suppurative under-dermatitis, phlegmon, furunculosis.

In case of vast septic wounds, it is necessary to inject Roncoleukin^® as part of complex therapy, intravenously, by drops (!) using 0.9 % solution of sodium chloride – one time (in the mentioned dose), then – subcutaneously (or oral) 2 - 3 injections with the interval of 24 - 48 hours.

In case of long-term nonhealing wounds, fistulas, residual abscesses, granulomatous formations, it is necessary to inject Roncoleukin^® with the dose of 100 000 - 250 000 ME with distilled water, locally, around the center of damage, one time; then 2 - 3 injections intravenously or subcutaneously with the dose of 1000 ME/kg.

To prevent burn disease and septic complications it is recommended to inject Roncoleukin^® intravenously, by drops (1) with the dose of 1000 - 2000 ME/kg, if necessary, the infusion of preparation is repeated in 24 - 48 hours.

10.2. Respiratory Diseases

In cases of acute bronchitis, pneumonia including viral pneumonia, it is recommended to inject Roncoleukin^®, 2 - 3 injections, in the course of complex therapy, intravenously, by drops (!) with the dose of 500 - 1000 ME/kg of body weight with the interval of 48 hours.

In case of chronic bronchial obstruction, the preparation is injected only after stopping the acute syndrome of hyperresponsiveness of bronchus, subcutaneously or intravenously, by drops (!), using 2 - 3 injections in the dose of 1000 ME/kg of body weight with the interval of 48 - 72 hours.

In order to prevent asthmatic assaults of horses with bronchial obstruction, it is necessary to inject Roncoleukin^® on a monthly basis, intravenously, by drops (!), two times with the interval of 48 hours using the mentioned dosage.

In case of alveolate emphysema of lungs, the preparation is injected to horses on the monthly basis, one time, intravenously, by drops (!) or subcutaneously using the mentioned dosage.

To prevent distribution of virus infections (influenza virus infection and etc.) Roncoleukin^® is injected intravenously, by drops (!) or subcutaneously, 2 - 3 injections with the dose of 1000 ME/kg to all the livestock contacting with diseased animals.

10.3. Atopic Dermatitis

In case of progressing contact dermatitis, photo-exanthema, multiform erythema, Roncoleukin^® is injected intravenously, by drops (!), with the dose of 1000 ME/kg one or two times in combination with a local therapy.

In cases of dermatitis with a detected specific inductor, perform injections of Roncoleukin^® right after the specific (antiparasitic, fungicide, antibacterial) therapy – intravenously, by drops (!) or subcutaneously, 3 - 5 injections with the interval of 48 hours.

10.4. Oncological diseases

Roncoleukin^® is used in case of scarifying melanotic sarcoma in order to localize neoplasms and regenerate damaged tissues. The preparation is injected subcutaneously with the interval of 48 - 72 hours, 3 - 5 injections with the dose of 1000 ME/kg of body weight.

In case of lymphoma, fibromatous enlargements and etc. the preparation is injected one time, intravenously, by drops (!) – then – subcutaneously, with the interval of 48 - 72 hours using the mentioned dosages.

10.5. Violation of Mineral Metabolism

In case of violations of mineral metabolism, incl. the detected endocrine genesis it is necessary to use Roncoleukin^® with the dose of 1000 ME/kg, two times, with the interval of 48 - 72 hours, and the corresponding diet is prescribed. The repeated course of treatment is performed in one month and then in two months.

10.6. Preventive Measures Against Adaptation Disease

Performing preventive measures against transport disregulation, it is recommended to inject Roncoleukin^® 24 - 72 hours before loading of horse, subcutaneously, intravenously (!) or oral, one time, with the dose of 1000 ME/kg from body weight.

During the period of competitions and the period of maximum physical activity, it is recommended to inject Roncoleukin^® in order to increase reserve possibilities of organism during the day of rest – once per week, subcutaneously, with the dose of 1000 ME/kg from the body weight (but not later than 48 hours before the competitions).

10.7. Preventive Measures Against Postoperative Complications

To prevent post-castration complications, and to accelerate regenerative processes, incl. in case of castration of cryptorches with a collateral surgical approach, it is recommended to inject Roncoleukin^® intravenously, by drops (!), or subcutaneously with the dose of 1000 ME/kg 48 hours before the operative treatment; then after the surgical intervention, subcutaneously, with the same dose.

In case of wound closure, surgical interventions at the belly wall, external genital organs, limbs, head and etc., it is recommended to inject the preparation right after the surgical aggression, intravenously or subcutaneously using the mentioned dose.

10.8. Disease Prevention of Colts

It is recommended to inject Roncoleukin^® at the 3 - 4th and 10 - 14th day after the birthday, intravenously, by drops (!), subcutaneously or oral with the dose of 1000 - 2000 ME/kg.

10.9. Immune Rehabilitation

It is recommended to inject Roncoleukin^® to perform immune rehabilitation after usage of corticosteroids and the course of other immunodepressants – 2 - 3 subcutaneous or intravenous (!) injections with the interval of 48 - 72 hours with the dose of 500 - 1000 ME/kg.

Roncoleukin^® is a universal measure for supporting quality of life of old and weak animals – 2 - 3 subcutaneous or intravenous injections (!) with the dose of 1000 ME/kg from the body weight, every month.

11. Medication of Cattle

Cattle are treated by Roncoleukin^® intravenously by jets, slowly (!) or subcutaneously with the dose of 1000 ME/kg from the weight of body. The preparation is injected to calves with the dose of 2000 - 3000 ME/kg. Roncoleukin^® also may be injected sublingually, intranasally and oral. In some cases the preparation may be injected in the form of circular (short) blockade and external applications.

The hypodermic injection of Roncoleukin^® to cattle may be accompanied by a short pain reaction ("burning") – up to 1 minute. In order to decrease this effect it is necessary to dilute the preparation, intended for injections, with water.

11.1. Infection Diseases (Bacterial, Fungal and Viral)

High efficiency of Roncoleukin^® usage is proven against such diseases as: infectious rhinotracheitis, virus diarrhea, respiratory cyncytial infection, parainfluenza-3, colibacillosis, salmonellosis, necrobacteriosis, clamidiosis and others.

In case of acute form of diseases it is recommended to use the preparation with the dose of 1000 ME/kg. The interval between injections is from 2 to 7 days. In the course of complex therapy of infection diseases it is necessary to use 2 - 3 injections of Roncoleukin^®, when curing heavy diseases – up to 5 injections.

If the preparation is included in the complex therapy of acute diseases we may observe:

quick normalization of blood biochemical measurements,
reduction of recovery terms.

If the preparation is included in the complex therapy of chronic diseases we may observe:

clinical recovery of animals,
normalization of antibody titers.

In addition, there is a possibility to perform vaccination of animals.

Necrobacteriosis. When curing the necrobacteriosis, it is recommended to use Roncoleukin^® as a mono-therapy, and in complex with antimicrobial preparations.

In the form of mono-therapy Roncoleukin^® is used subcutaneously or intravenously with the dose of 1000ME/kg, 2-3 injections with the interval of 7 - 10 days. If the weather is hot, 30 minutes before the injection of Roncoleukin^®, it is recommended to inject sodium benzoate using the recommended dosage in order to decrease the load on the load on cardiovascular system. In case of vaccination, it is necessary to use modern vaccines against necrobacteriosis of cattle.

The strategy of usage of complex scheme, intended for struggling with necrobacteriosis, is as follows:

Strict adherence to animal sanitation requirements for cattle management and harmony of feeding rations;
Usage of modern vaccines against necrobacteriosis of cattle;
Edging and clearing of hoofs no less than 2 times per year (excluding cows in the last third of pregnancy). Before and after the procedure of edging and clearing of hoofs, the surface of hoofs and of hygienic surgical instrument (butteris and rasp, chisel and hammer butt) must be moistened abundantly with Monklavit-1.
If the diagnosis of necrobacteriosis is identified, it is necessary to perform the following measures:

the reservoir with the length of not less than 2 meters, with an enough level of Monklavit-1 should be installed at the exit to the pen and to the milk house to cover hoofs of passing cattle.
affected parts of limbs must be washed by the preparation 2 times per day. The baths with Moklavit-1 provide the biggest effect for damaged hoofs. In order to treat damaged hoof the animal should stay in the reservoir with the preparation for 30 minutes, 1 - 2 times per day. The bactericidal properties of the preparation are strengthened when it is heated at the boiling-water bath to the temperature of up to 40?С;
perform activation of immune system using Roncoleukin^®: subcutaneously or intravenously, with the dose of 1000 ME/kg from the weight of animal, 2 - 3 injectins, with the interval between injections of 7 - 10 days;
moisten bandaging material applied to the gangrenous, ulcerous surface with Monklavit-1 after the surgical debridement; remove pseudomembranes and necrotizing areas of mucous mouth cavity and irrigate it by the preparation 2-3 times per day, the products of purulent discharge, dissected necrotizing tissues and used material (sponges and etc.) must be gathered and burned. In case of necrobacteriosis the guaranty of successful treatment is radical remove of detached and dead tissues;
during feeding, drench forage with Monklavit-1 with the dose of 200 - 250 ml for one animal, once per day;
perform humid disinfection of the places where animals stay (livestock buildings, boxes) after their mechanical purification with Monklavit-1 with the dose of 0.5 l/m2 f the surface, once per day.

Clamidiosis. When curing Clamidiosis of cattle it is recommended to inject Roncoleukin^® in the course of complex treatment three times with the interval of 7 days and the dose of 1000 ME/kg. As a result, the clamidiosis agents are freed. To prevent clamidiosis of cattle the preparation is used during the vaccination as the adjuvant vaccine (p.11.4).

11.2. Respiratory Diseases

To prevent viral diseases (most often viruses of parainfluenza-3, respiratory-syncytial, infectious rhinotracheitis; scarcer adeno-, toro-, reo-, parvo-, rhino-viruses, viruses of diarrhea, influenza and immune deficiency), mycoplasmosis, pasteurellosis and other respiratory disease, it is recommended to include Roncoleukin^®into the complex scheme of therapeutic measures, at that, the preparation more effective if used for calves after their birth at the first day for stimulation of inborn immunity (p.11.5), before their transfer from the preventive clinic to the calf house (p.11.6), and during vaccination as an adjuvant vaccine (11.4).

During complex treatment of acute bronchitis, pneumonia, incl. virus origin, it is recommended to inject Roncoleukin^®, in the course of complex therapy, intravenously (!) or subcutaneously with the dose of 500 - 1000 ME/kg of body weight with the interval of 24 - 72 hours, 2 - 3 injections. The dose is increased up to 2000 - 3000 ME/kg for calves. As a result, the recovery starts 5 days earlier, the safety and weight are increased on 19 %

11.3. Diseases of the Digestive Tract

To prevent infectious diseases of the digestive tract (salmonellosis, colibacillosis, coronaviral enteritis of calves, reovirus infection, anaerobic enetherotoxemia, parvovirus infection, rotavieus infection of calves and etc.) It is recommended to use Roncoleukin^® for calves after their birth at the first day for stimulation of inborn immunity (p.11.5), before their transfer from the preventive clinic to the calf house (p.11.6) and during vaccination as an adjuvant vaccine (11.4).

During the complex therapy of gastrointestinal problems it is recommended to use the preparation with the dose of 2000 - 3000 ME/kg. The interval between injections is 48 hours, 2 - 3 injections of Roncoleukin^®are used, when treating heavy forms of disease – up to 5 injections.

11.4. Adjuvant Vaccine

It is recommended to use Roncoleukin^® simultaneously with vaccination, but using different syringes, subcutaneously, with the dose of 1000 МЕ/kg, once.

As a result:

the immune reaction of organism on introduction of vaccine is increasing - antibody titers in the serum of blood of animals, which were treated with Roncoleukin^® and the vaccine, are 1.5 - 3 times higher in comparison with animals, which were vaccinated without usage of Roncoleukin^®..
the possibility of successful vaccination is increased – the immune reaction to introduction of vaccine together with Roncoleukin^® is observed for 100 % of animals.

11.5. Stimulation of Inborn Immunity

To stimulate the inborn immunity of calves during the first days after their birth it is recommended to inject the preparation Roncoleukin^® subcutaneously with the dose of 100 000 ME for one animal, one time. As a result, the disease incidence is decreased and the safety of calves is increased on 15 %.

11.6. Preventive Measures Against Adaptation Diseases

Roncoleukin^® is also used as a measure of stress release resulted of various manipulations, transportation, rearrangement, bonitation and etc.

It is recommended to use the dose of 1000 ME/kg, one time, but not later than 48 hours before the beginning of proposed actions.

As a result:

the immune reaction of organism is increased,
animal easily undergoes various manipulations, transportation, and etc.

11.7. Traumatic Injuries

In case of vast septic wounds, it is necessary to inject Roncoleukin^® as part of complex therapy, intravenously (!) or subcutaneously using 0.9 % solution of sodium chloride – one time (in the mentioned dose), then – subcutaneously 2 - 3 injections with the interval of 24 - 48 hours.

In case of long-term nonhealing wounds, fistulas, residual abscesses, granulomatous formations, it is necessary to inject Roncoleukin^® with the dose of 100 - 250 thousands ME with distilled water, locally, around the center of damage, one time; then 2 - 3 injections intravenously or subcutaneously with the mentioned dose.

11.8. Preventive Measures Against Postoperative Complications

To prevent post-castration complications, and to accelerate regenerative processes, incl. in case of castration of cryptorches with a collateral surgical approach, it is recommended to inject Roncoleukin^® intravenously, by jets, slowly (!), or subcutaneously with the dose of 2000 ME/kg 48 hours before the operative treatment; then after the surgical intervention, subcutaneously, with the same dose.

11.9. Stimulation of Desire

Roncoleukin^® is used for normalization (reconstruction) of sexual repeatability of cows with hypovarianism, penetrant long-term anaphrodisia, with the dose of 1000 ME/kg, two times, with the interval of 24 - 48 hours.

As a result, using Roncoleukin^® as a monotherapy:

desire occurs without usage of hormonal excitors,
normalization of desire and ovulation starts 60 % earlier in comparison with standard methods of treatment (on an average in 18 - 20 days, for 85 - 90 % of cattle).

11.10. Immune Rehabilitation

Roncoleukin^® is recommended for injection in order to provide immune rehabilitation after the course of usage of corticosteroids and other immunodepressants – 1 - 2 injections with the interval of 48 - 72 hours using the mentioned dose.

To improve the immunobiological reactivity of organism in case of parasitic diseases, it is recommended to use Roncoleukin^® with the dose of 1000 ME/kg, one time.

12. Medication of Small Cattle

The preparation Roncoleukin^® is used intravenously, slowly (!) or subcutaneously with the dose of 2000 - 3000 ME/kg and the interval of 24 - 72 hours. The dose may be increased to 5000 ME/kg for young stock.

Prescriptions for usage are the same as for cattle.

13. Medication of Swines

The preparation is used subcutaneously, in form of aerosol or drink with the dose of 2000 - 5000 ME/kg with the interval of 24 - 72 hours, the dose may be increased up to 5000 ME/kg for piglets. In specific cases, it is possible to inject the preparation in the form of circular (short) blockade and external applications.

The hypodermic injection of Roncoleukin^® may be accompanied by a short pain reaction ("burning") – up to 1 minute. In order to decrease this effect it is necessary to dilute the preparation, intended for injections, with water.

13.1. Infection Diseases (Bacterial, Fungal and Viral)

In cases of acute infectious diseases, it is recommended to use the preparation with the dose of 2000 ME/kg, in cases of chronic diseases – with the dose of 3000 МЕ/kg. The interval between introductions is 24 - 48 hours. In the course of complex therapy of infection diseases it is necessary to use 2 - 3 injections of Roncoleukin^®, when curing heavy diseases – up to 5 injections.

In case of respiratory diseases of swine, incl. reproductive-respiratory syndrome of swine, circus-virus disease of swine (syndrome of after-removable multisystem exhaustion), influenza, Aujeszky's disease, profilerative-necrotizing pneumonia of swine, hemophilic polyserositis of swine (Glesser's disease), enzootic pneumonia (mycoplasmosis), actinobacillus pleuropneumonia (hemophilic pleuropneumonia), infection atrophic rhinitis, pasteurellosis and etc. it is recommended to include Roncoleukin^®into the complex scheme of therapeutic measures.

The recommended scheme of piglet treatment
В Ф К ТВ Р ТВ Р КЧС
/__/__/_____/____/____/____/__________/________/_________
0 2 3 10 15 25 26 breaking in to milk 40 45 days of life

Note: В – injection of vitamins; Ф -ferroglukin; К – castration; ТВ – vaccine against respiratory syndrome ; КЧС -vaccination against classical hog cholera; Р – injection of Roncoleukin^®.

Roncoleukin^® is injected subcutaneously with the dose of 50 000 МЕ per piglet at the age of 25 days and repeatedly with the dose of 75 000 ME per piglet at the age of 40 days. As a result of usage of Roncoleukin^® in accordance with this scheme when transferring piglets into the groups intended for feeding, their safety increases on 7 %, and the daily average body-weight increase is 70 g more, at the same time the incidence rate of bronchopneumonia decreases, it is presented in the rate of compulsory slaughter, which is shortened on 4.6 %.

Curing acute bronchitis, pneumonic fever, Roncoleukin^® is injected subcutaneously, 2 - 3 injections within the course of complex therapy in the dose of 2000 - 3000 МЕ/kg from the body weight, with the interval of 24 - 72 hours. The dose for piglets is increased up to 5000 ME/kg.

To prevent the digestive tract diseases of swine, incl. inoculable gastroenteritis, epizootic virus diarrhea, coronaviral encephalomyelitis (vomitory disease), colibacillosis, salmonellosis, anaerobic eneterotoxemia, dysentery, digestive digestive adenomatosis of swine and etc., it is recommended to include Roncoleukin^® into the complex scheme of therapeutic measures.

At the same time, it is recommended to use Roncoleukin^® subcutaneously, at the 1 - 3rd days of life with the dose of 5000 - 10000 МЕ per piglet, at the age of 25 days – 50000 ME per piglet and at the age of 40 days – 75000 ME/piglet.

If the preparation is included in the complex therapy of acute infectious diseases we may observe:

quick normalization of blood biochemical measurements,
reduction of recovery terms.
If the preparation is included in the complex therapy of chronic infectious diseases we may observe:
clinical recovery of animals,
normalization of antibody titers.

In addition, there is a possibility to perform vaccination of animals.

13.2. Adjuvant Vaccine

It is recommended to use Roncoleukin^® simultaneously with vaccination, but using different syringes, subcutaneously, with the dose of 2000 - 3000 МЕ/kg, once.

As a result:

the immune reaction of organism on introduction of vaccine is increasing -antibody titers in the serum of blood of animals, which were treated with Roncoleukin^® and the vaccine, are 1.5 - 3 times higher in comparison with animals, which were vaccinated without usage of Roncoleukin^®.
the possibility of successful vaccination is increased – the immune reaction to introduction of vaccine together with Roncoleukin^® is observed for 100 % of animals.

13.3. Stimulation of Inborn Immunity

During the first days of life for stimulation of inborn immunity of piglets it is recommended to inject Roncoleukin^® subcutaneously with the dose of 5000 - 10000 ME per piglet, one time. As a result, the disease incidence is decreased and the safety of piglets is increased on 15 %.

13.4. Traumatic Injuries

In case of acute injuries, accompanied by failures of skin, walls and lower margins of hoof and soft tissues, Roncoleukin^® is injected subcutaneously, one time, with the dose of 2000 - 3000 ME/kg, in order to prevent suppurative complications.

In case of vast septic wounds, it is necessary to inject Roncoleukin^® as part of complex therapy, using 0.9 % solution of sodium chloride – one time (in the mentioned dose), then – subcutaneously 2 - 3 injections with the interval of 24 - 48 hours.

In case of long-term nonhealing wounds, fistulas, residual abscess, granulomatous formations, it is necessary to inject Roncoleukin^® with the dose of 500-1000 thousand. ME using distilled water locally around the center of damage, one time; then – subcutaneously, 2 - 3 injections using the mentioned dosage.

13.5. Preventive Measures Against Postoperative Complications

To prevent post-castration complications, and to accelerate regenerative processes, incl. in case of castration of cryptorches with a collateral surgical approach, it is recommended to inject Roncoleukin^® subcutaneously with the dose of 3000 ME/kg 48 hours before the operative treatment; then after the surgical intervention, subcutaneously, with the same dose.

13.6. Immune Rehabilitation

Roncoleukin^® is recommended for injection in order to provide immune rehabilitation after the usage of corticosteroids and other immunodepressants – 1 - 2 injections with the interval of 24 - 48 hours using the mentioned dose.

To improve the immunobiological reactivity of organism in case of parasitic diseases, it is recommended to use Roncoleukin^® with the dose of 2000 ME/kg, one time.

13.7. Preventive Measures Against Adaptation Disease

Roncoleukin^® is used as a measure for stress release in case of various manipulations, transportation, breaking in to milk, but not later than 48 hours before the beginning of proposed actions.

It is recommended to use the dose of 2000 ME/kg one time.

As a result:

the immune reaction of organism is increased,
animal easily undergoes various manipulations, transportation, bonitation and etc.
the clinical picture of diarrhea of piglets during their habituation to eat combined feed and after breaking in to milk is absent.

14. Medication of Fur Animals and Rodents

The preparation is used with the same dosages and with the same prescriptions as for treatment of small domestic animals.

15. Medication of Farming Birds

15.1. Adjuvant Vaccine

The preparation Roncoleukin^® is used as an adjuvant vaccine together with the vaccine (for example: during vaccination against Marek's, Gamboro's, Newcastle's diseases, infectious laryngotracheitis and etc.) in one or several various syringes, subcutaneously, intramuscularly, intranasally and in the form of drink or aerosol with the dosage of 1000 - 3000 МЕ/kg, one time.

To dilute Roncoleukin^® the following substances are used: 0.9 % solution of sodium chloride – when the preparation and the vaccine are injected separately; vaccine diluter – when the preparation and the vaccine are injected in combination.

As a result:

the immune reaction of organism is increased,
the possibility of successful vaccination is increased,
the safety of youngsters is increasing,
the increase of bird body weight is observed.

15.2. Stimulation of Inborn Immunity

To stimulate the inborn immunity, it is necessary to use Roncoleukin^® subcutaneously, intramuscularly, in the form of drink or aerosol.

As a result:

the natural resistance of organism is increasing (the content of lysozyme in the tracheobronchial secrete is growing, the content of vitamin A in the liver of chickens is increasing).
the safety young stock is increasing,
the content of erythrocytes, leucocyte, common protein and blood pigment is increasing.

It is necessary to note, that hatchable eggs of breeding poultry, receiving the preparation at the age of one day were characterized as follows:

lysozyme activity of received hatchable eggs is 10.6 % higher, that characterizes higher vital activity of the egg,
eggs' fertilizing is 2% higher,
weight of received eggs is higher,
breeding of healthy youngsters is 3.8% higher.

Usage of the preparation Roncoleukin^® for chicken-broilers provides a possibility to decrease significantly the expenses on medicinal preparations, and the possibility appears to receive the poultry stock grown without antibiotics and to decrease the feed consumption on one set bird.

16. Medication of Wild and Exotic Animals

The preparation is used intravenously, in jets, slowly (!) or subcutaneously with the dose of 1000 - 10000 ME/kg and the interval of 24 - 72 hours (depending on the size of animal).

The preparation is used for even-hoofed mammals and camels with the same doses which used for treatment of cattle or small cattle.

The preparation is used for solid-hoofed animals with the same doses which used for treatment of horses.

When curing reptilians the same doses are used as for rodents.

When curing pinnipeds the doses of 3000 - 5000 ME/kg are used in 24 - 72 hours

When curing exotic birds, there is also a possibility to use intranasal and oral methods of preparation injection.

17. MEDICATION OF FISH

17.1. Medication of Sturgeons

To prevent origination of complications after the surgical intervention, it is recommended to perform one intravenous injection of Roncoleukin^® before the surgical intervention with the dose 2000 ME/kg from the weight of fish body. After the surgical intervention, it is recommended to perform two hypodermic injections of the preparation with the interval of 24 hours with the dose of 5000 ME/kg from the body weight. It is necessary to dilute the preparation with water for injections or with sterile 0.65% physiologic saline wit the volume from 0.5 to 3.5 ml (depending on the weight of fish).

To increase viability of sturgeon youngsters and their hybrids (as an immune corrector or an antistress measure) it is recommended to inject Roncoleukin^® oral. Before usage the preparation should be diluted with a physiologic saline with the dose of 16ml of solution for 1 kg of feed. Injection of Roncoleukin^® in the feed is performed by sputtering the received solution on the grain with following greasing; one time 7 days before the expected single stress with the optimal dose of 6000 ME/kg of fish body weight or by three day course of treatment with the interval of 48 hours with the dose of 2000 ME/kg of the body weight in case of stresses connected with handling.

For youngsters with weight up to 100 g it is recommended to use baths with Roncoleukin^® for the period of half an hour with the dose of 300 000 - 400 000 МЕ / 100l of water with termination of water exchange and forced oxygenation.

As a result, injection of Roncoleukin^®:

promotes active regeneration of damaged tissues of sturgeons during the surgical traumatization and earlier terms of reparation;
the number of erythrocytes and leukocytes in the blood is increasing, it gives evidence about the stimulation of functionality of hemogenesis activity, as well as in some doses it stimulates the generation of immunoglobulins;
positively impacts on cellular immunity, firstly to the active proliferation of lymphocytes and restoration of phagocytic function of heterophilic leukocytes of sturgeons and their hybrids;
optimizes metabolic processes of organism and stimulates the immune system, promotes quick and significant areal growth of sturgeons of younger and middle age categories even in the postsurgical period;
it gives the therapeutic effect at the 7th day on an average with the prolongation of it to 15 - 45 days depending on the dose, method of injection, as well as the reasons of immune correction;

Influence of Roncoleukin^® on the organism of sturgeons has common features and functional similarity as if it impacts on the organism of homoiothermal animals.

17.2. Medication of Salmons

To prevent fungal infections and increase of caviar and larva immunity it is recommended to treat the caviar of trout by Roncoleukin^® with the dose of 250 000 МЕ/100 l of water with the exposition of 15 minutes;

In order to prevent bacterial disease of trout youngsters, injection of preparation may be performed before appearance of first signs of infection. At that, the most effective injection of Roncoleukin^® is performed in the feed when youngsters transfer to active feeding (while rising for floating) in case of one treatment with the dose of 250 000 МЕ/100 l water with the exposition of 15 minutes;

Performing injection of Roncoleukin^® in the feed, the therapeutic effect has the following scheme: using the method of irrigation with the dose of 4000 ME/kg of ichtyomass in three courses of treatment, the length of each course is 3 days, the interval between the courses is 10 - 14 days, the preparation is injected during one feeding. The complex treatment using antibiotics, selected as a result of researches of microbial strains for response to these preparations, is possible. Injection of Roncoleukin^®in the feed also promotes increasing of the body weight of trout youngsters.

It is recommended for the producers of trout to inject Roncoleukin^® during the post-spawning period. To perform therapeutic measures the preparation is injected using the method of irrigation with the dose of 2000 ME/kg of the ichtyomass by three courses; the length of each course is one day, the interval between the courses is five days, the preparation is injected during one feeding. At that, activation of regeneration processes and the increase of immunity for secondary injections are registered.

17.3. Medication of Cyprinid Fish

It is recommended to inject Roncoleukin^® oral to cyprinid fish by irrigating the feed with the dose of 2500 ME/kg from the fish weight, three times with the interval of 48 hours.

As a result, we observe growing of:

level of hemoglobulin on 11 %;
phagocytic activity of neutrophil in 5 times;
average weight of fish on 6.4 %.

When performing preventive measures and treatment of spring viremia of carps, it is recommended to inject Roncoleukin^® oral irrigating the feed with the dose of 1000 - 2500 ME/kg from the weight of fish, one time.

As a result: