Veterinary implantable drug immunostimulating actions (options)

 

The invention relates to veterinary medicine. The drug contains melatonin or melatonin with ximedona, biodestruction polymer base and technological additives (or plasticizer). The proposed three medicinal composition of the following composition, wt.%: melatonin 5-25, ksimedon 5-25, propeller-EA (polymer) 89,95-35, the plasticizer of 0.05-15; melatonin 10-50, derivatives of cellulose 89,95-35, technological additives of 0.05-15. The drug increases the safety, nonspecific resistance and productivity with accelerated breeding of fur-bearing animals and other farm animals. 2 S. and 2 C.p. f-crystals, 3 tables.

The invention relates to veterinary medicine and can be used in fur farming and livestock, particularly pigs.

It is known the use of synthetic melatonin to regulate the biological rhythm of the life processes of animals [Patent 78305/81 Australia; Patent 38111/85 Australia] . It is also known use for these purposes veterinary implants containing melatonin or related chemicals class of indole, a polymeric carrier and a coating for an implant of a physiologically compatible polymer [Patently composition, the method of making them was technologically difficult. More attractive are veterinary drugs, developed in Russia, containing melatonin and a polymer base, facilitating maturing hairline fur-bearing animals [A. S. 1579489 the USSR, MCI And 01 To 67/02; Patent RU 2122787, IPC 6 AND 01 TO 67/02, AND 61 TO 31/51 // BI 9, 1999]. But they have some significant drawbacks, namely: contain partially biodestruction a polymer base, which leads to incomplete "release" melatonin; in addition, these drugs effective for mandatory inclusion in the diet Perevalova protein in the amount of 6-8 g per 100 kcal of food.

Known use for breeding fur-bearing animals veterinary implantable drug containing synthetic hormone of the pineal gland - melatonin on the polymeric base (prototype) [Patent RU 2096044, MCI And 61 To 47/30 (a 61 K 47/30, 38:22). // BI 32, 1997]. The use of this drug in fur farming allows the slaughter of animals for 1.5-2 months earlier than the standard time frame of the face and get fur products area of 10-15% larger than the standard.

However, the application of the known implant does not always ensure the safety of fur-bearing animals (typically, patients Aleuts is OK is finding ways and means of protecting livestock from disease viral plasmacytosis or Aleutian disease of mink. The disease brings enormous economic damage resulting from the great falls adult animals (70-80%) and puppies first two weeks of life, a significant number of blank (which produced no offspring), disadvantaged schenyaschayasya and Melpomene females, increased sterility in males and deterioration fur [Ducor I. I. Diseases of fur-bearing animals. - M. : Kolos, 1973, S. 83-94]. The source of infection is sick animals, in the body where the virus lives for a long time. The virus is located in the blood, brain, kidney, liver, spleen, salivary glands, mesenteric lymph nodes and intestines.

The disease is characterized by slow, latent, and long for, initially accompanied by a small case of animals. As the disease development and accumulation of sick animals is a big waste of mink characteristic of this disease clinic and the anatomic changes. In the mechanism of development of the disease there are two stages: infectious and autoimmune. The first stage is characterized by the multiplication of the virus, the formation of plasma cells producing anti-viral antibodies, and f is onogo complex cells, the formation of autoantigens and autoantibodies that lead to the development of immunopathologically processes in organs and mortality [Karslad L. New Iork, Springer, 1967, v. 40, p. 9-21].

It is known that the use for therapeutic purposes of immunodepression of methotrexate and 6-mercaptopurine causes significant decrease in the mitotic activity of lymphoid tissue and decrease plasmocytomas infiltration of organs. The disadvantage of the above-mentioned compounds is their high toxicity. However, immunosuppressants and immunomodulators (levamisole) and hormones can be successfully used as a therapeutic tool that allows you to extend the life of mink to slaughter period [Ducor And. And. and other Diseases of fur-bearing animals. Ed. 3-E. - M.: Kolos, 1984, S. 78-87].

The purpose of the invention is a new implantable veterinary drugs with immunostimulating action and expanding Arsenal of known means to increase security, nonspecific resistance and productivity of fur-bearing animals under the fast track their cultivation and other farm animals.

This goal is achieved, we offer veterinary compositions and their use in fur farming and pig breeding. We offer veterinary composition pre is again and technological additives (or plasticizer).

As the polymer base used water-soluble derivatives of cellulose (e.g. microcrystalline cellulose, hydroxyethyl cellulose, methylhydroxypropylcellulose, methylcellulose, methylhydroxyethylcellulose, hydroxyethylmethylcellulose), preferably microcrystalline cellulose (MCC) with a degree of polymerization of 150 to 200, with the use of additives to give the composition the necessary mechanical and prolonging properties or biodestruction polymers based on ethylcyanoacrylate (propeller-EA) with the use of plasticizers.

As technological additives used water-soluble derivatives of cellulose such as methyl cellulose with a degree of polymerization of 150 to 250, carboxymethylcellulose with a degree of polymerization of 400-700 or its sodium salt, oxypropylation with a degree of polymerization of 500 to 1,000. The above derivatives of cellulose are known components of widely used medicines such as Solcoseryl jelly (stimulator of regeneration of skin cells with the use of Na-salt of carboxymethyl cellulose), Riboxin (for regulation of metabolic processes, contains methylcellulose), Finlepsin, Ancyra B, Lamy is este plasticizers can be used esters (ethyl, propyl, butyl, allyl, phenyl) phthalic acid, alkilinity, triacetin. [Patent RU 2096044, MCI AND 61 TO 47/30 (a 61 K 47/30, 38:22) // BI 32, 1997].

As the second medical component use ksimedon - 1-(-oxyethyl)-4,6-dimethyl-1,2-dihydro-2 - oxopyrimidine. Ksimedon is a promising drug, well-proven in the treatment of purulent-inflammatory postoperative complications, burns is a new drug effective in the treatment of acute pneumonia, senile, diabetic and radiation long-term healing of wounds [Patent RU 2019176, MKI a 61 K 31/505 // BI 6, 1995; Patent RU 2063752, MKI a 61 K 31/505 // BI 20, 1996; Patent RU 2082402, MKI a 61 K 31/505 // BI 18, 1997]. By order of the Ministry of health of the Russian Federation from 07.12.93 287 ksimedon approved for use in medicine and entered in the register of medicines for the treatment of burn patients [Protocol 22 farmkomiteta the USSR Ministry of health from 26.12.86; Order 287 MOH from 07.12.93 on making Ximena in the State Register of medicinal products permitted for use in medical practice and production]. Compared with such drugs as retabolil, methandrostenolone, levamisol, ksimedon is a drug, blablabal any hormonal activity and does not affect the endocrine homeostasis.

We offer 3 songs veterinary implant of the following composition, wt.%: 1. Melatonin - 5-25 Ksimedon - 5-25 Propeller-EA (polymer) - 89,95-35 Plasticizer is 0.05-15 2. Melatonin - 10-50 Derivative of cellulose - 89,95-35 Technological additive is 0.05-15 3. Melatonin - 5-25 Ksimedon - 5-25
Derivatives of cellulose 89,95-35
Technological additives 0.05 to 15
The proposed compositions and their use earlier in the literature were not.

The introduction of biodestruction polymer Ximena along with melatonin resulted in an unexpected (non-obvious). After implantation of drug Minks, patients with viral plasmocytosis, the disease has acquired the character of a slow subclinical infection without activating autoimmune phase of the disease, which contributed to the livability of mink to slaughter period when the short growing at 1.5-2 months before the standard terms and obtaining fur products area at 18-20% compared with untreated animals that improved earlier results [Patent RU 2096044, MCI AND 61 TO 47/30 (a 61 K 47/30, 38:22) // BI 32, 1997]; application of the proposed drugs in pigs led to a safety and a significant increase in body weight nursing porosa provides the desired effect, above 25 wt.% (songs 1, 3) and 50 wt.% (composition 2) is impractical due to increased cost of the drug, the stability and efficiency of the dosage form.

The content of polymeric bases below 35 wt.% and above 89,95 wt.% does not provide the necessary prolonging properties of the drug. The introduction of plasticizers and additives can improve the physico-mechanical characteristics of the drug and avoid the appearance of phase heterogeneity structure of the dosage form.

The use of plasticizer and additives above 15 wt.% leads to disruption of the strength characteristics of the drug, is below 0.05 wt.% does not provide the necessary plasticity and physico-mechanical characteristics of the composition.

Dosage form of the proposed compositions are tablets cylindrical mass 0,0400,010 g diameter 2,0-2,4 mm brown (shades not standardized). The preparation was carried out analogously to [Patent RU 2122787, MCI AND 01 TO 67/02, AND 61 TO 31/51 // BI 9, 1999].

In comparison with the known veterinary means, on the basis of melatonin offer veterinary preparations containing melatonin or melatonin with ximedona possess significant mainly in fur farming in accelerated raising mink contributes to the livability of mink to slaughter period, with the improvement of existing indicators: short growing at 1.5-2 months, and obtaining a fur product area, 18-20% higher compared to untreated animals.

2. The drug containing melatonin and ksimedon, based biodestruction polymer (compositions 1, 3) fur farming in accelerated raising mink contributes to the livability of mink, patients with viral plasmocytosis to slaughter period while improving the previously achieved results: the short growing at 1.5-2 months and getting fur products area, 18-20% more of it compared to untreated animals. As a result of action of the drug containing melatonin and ksimedon, the development of viral plasmocytosis experimental mink becomes sluggish subclinical infection without activation of the autoimmune phase of the disease.

3. The use of drugs in pig production contributes to the activation of anabolic processes, leading to a significant increase in body weight suckling piglets (up to 48% compared to control).

4. The inventive preparations possess adaptogenic and stimulating effect, increase the nonspecific resistantanti body piglets in the postnatal period of development.

As was shown in clinical trials to offer implantable drugs Ablaut a new medicinal product with unexpectedly higher medical and immunostimulating effect.

The experiment showed that implantation model veterinary compositions containing as activitiesthese substances only ksimedon and biodestruction polymer base (derivatives of cellulose with technological additives or poliatilenaksida with plasticizer) the mink does not provide accelerated maturing hairline fur-bearing animals, the gain of body weight and increasing the area of skin. The maturation of fur in the experimental animals and their slaughter in this case occurred in the same period that have not been treated with drugs mink (PL. 2).

During implantation model veterinary compositions containing only ksimedon and biodestruction polymer base with technological additives (or plasticizers), pre-weaned piglets was not observed significant differences in weight gain in live weight of the experimental animals compared to control.

High efficiency of the proposed veterinary implantable drugs confirm the following examples.

Example 1. Evaluation of the effectiveness of the veterinary preparation containing melatonin.

To assess the effectiveness of the claimed veterinary drugs was studied the kinetics of release ("release") active substances of the pulse// BI 32, 1997]. The sample - Melipal (prototype) - veterinary drug patent [Patent RU 2096044, MCI AND 61 TO 47/30 (a 61 K 47/30, 38:22) // BI 32, 1997] composition, wt.%: melatonin - 10-40; propeller-EA (polymer) - 89,95-55,5; the plasticizer is 0.05 to 4.5 in the amount of 10 mg was placed in a volumetric flask with a capacity of 50 ml, was added 50 ml of liquid TEVA with preservative, closing the flask with a stopper and placed in a thermostat at a temperature of 37oC. samples of 5 ml were collected at 2, 10, 20, 30, 40, 50, 60 the day of the experiment. After every single sample in the volumetric flask was added 5 ml of liquid TEVA with preservative. The content of active substance in the samples was determined by gas chromatography on the chromatograph firm "Waters" (LC/GPC-244) or any other model, equipped with a UV spectrophotometric detector (wavelength 254 nm; sorbent - silicagel18grain 5-18 μm; eluent - acetonitrile-water; temperature 25oC).

Example 2. Analogously to example 1 tests were subjected to declare veterinary drug composition, wt.%:
Melatonin - 10
Microcrystalline cellulose (MCC) - 89,95
Technological additives - 0,05
Example 3. Analogously to example 1 tests were subjected to declare veterinary drug composition, wt.%:
Melatonin - 10
Oxypropylene terinary the drug composition, wt.%:
Melatonin - 50
MCC - 35
Technological additives - 15
Example 5. Analogously to example 1 tests were subjected to declare veterinary drug composition, wt.%:
Melatonin - 50
Oxypropylation - 35
Technological additives - 15
Example 6. Analogously to example 1 tests were subjected to declare veterinary drug composition, wt.%:
Melatonin - 5
Ksimedon - 5
The propeller-EA (polymer) - 89,95
Plasticizer - 0,05
Example 7. Analogously to example 1 tests were subjected to declare veterinary drug composition, wt.%:
Melatonin - 25
Ksimedon - 25
The propeller-EA (polymer) - 35
Plasticizer - 15
Example 8. Analogously to example 1 tests were subjected to declare veterinary drug composition, wt.%:
Melatonin - 5
Ksimedon - 5
Microcrystalline cellulose (MCC) - 89,95
Methyl cellulose (MC) - 0,05
Example 9. Analogously to example 1 tests were subjected to declare veterinary drug composition, wt.%:
Melatonin - 25
Ksimedon - 25
MCC - 35
MC - 15
Example 10. Analogously to example 1 tests were subjected to declare veterinary drug composition, wt.%:
Melatonin - 5
Ksimedon - 5
ICC - 89,95
Sodium carboxymethyl cellulose (NaKM) - 0,05
Example 11. A /> Ksimedon - 25
MCC - 35
NaKM - 15
Example 12. Analogously to example 1 tests were subjected to the sample model composition composition, wt.%:
Ksimedon - 10
The propeller-EA (polymer) - 89,95
Plasticizer - 0,05
Example 13. Analogously to example 1 tests were subjected to the sample model composition composition, wt.%:
Ksimedon - 10
ICC - 89,95
MC - 0,05
Example 14. Analogously to example 1 tests were subjected to the sample model composition composition, wt.%:
Ksimedon - 50
MCC - 35
MC - 15
Thus, we studied the sample of veterinary medicine of the prototype, made by the [Patent RU 2096044, MCI AND 61 TO 47/30 (a 61 K 47/30, 38:22) // BI 32, 1997] and the samples of the inventive veterinary drugs (examples 2-14). All samples were placed in krovezamenauschie solution at the same time. The test time was 60 days. The results are presented in table. 1.

As can be seen from the data given in table. 1, biodestruction the polymer base containing either polymer propeller-EE and a plasticizer, or a water-soluble derivative of cellulose with technological additives (methyl cellulose, sodium carboxymethyl cellulose), provides a relatively uniform "release" melatonin and melatonin with ximedona claimed in veterinary the tray, the time extension was not more than 35 days.

Example 15. Testing of prototypes declare veterinary drugs in fur farming.

In fur farms "Kosakowski" of the Republic of Tatarstan were tested prototypes of products containing melatonin, melatonin and ksimedon, on the basis of microcrystalline cellulose on the mink. The effectiveness of the proposed drugs was assessed by comparison with the efficiency of known drug Melipal (prototype) containing melatonin (the composition indicated in example 1). To evaluate the effectiveness of the inventive compositions tested were also subjected to the composition of the following composition, wt.%: ksimedon - 10, MKC - 89,95, MC - 0,05. As control were used animals not treated with the drug containing melatonin. The drugs were injected subcutaneously in the area between the blades 1 dose on the head. The youngsters were treated in the period from 25 June to 10 July. Side effects and complications in the use of the drug was observed. In the site of implantation of the drug inflammatory processes in the inner and outer layers of the skin and subcutaneous tissue was absent. The study of the dynamics of changes in body weight showed that the difference in the gain in live weight of the animals experienced (groups 2, 3, 4 is - 09.11.01. Furs after manufacture consistent with GOST 7906. The results are given in table. 2.

Example 16. Carrying out morphological studies of the impact of veterinary drugs, containing melatonin and ksimedon on the organs and tissues of mink.

To study the influence of the developed veterinary sustained-release preparations containing synthetic melatonin and ksimedon, on the body ball Aleutian disease of mink conducted field tests of prototypes on narkologicheskoi farm animal-breeding sovkhoz "Kosakowski" Pestrechinsky area RT.

Test was made 3 test sample preparation: 2 sample containing melatonin and ksimedon (samples 3, 4 PL. 2); 1 sample containing melatonin, microcrystalline cellulose (sample 2 table. 2). The effectiveness of the prototypes were evaluated in comparison with the prototype sample (sample 1 table. 2). In the experiment had used 100 heads of Minks standard color 4 months of age, divided into 5 groups: 1-4 group experienced a 6-group I - control (animals not treated with drugs), PL. 2.

The tested drugs were implanted in a single dose (single grains) each animal in the subcutaneous tissue region is ecchi and needle sterilized with 70% alcohol.

Morphological, histological and histochemical studies were subjected samples of tissues and organs of animals taken for research in killing day (end of experiment).

Liver. Histological changes in the liver of mink exposed to prolonged effects of melatonin and Ximena, was characterized by the development of the structural organization of the body. Hepatocytes were characterized by heterogeneity in the size and structure of the cytoplasm. In the cytoplasm of most cells of the parenchyma in the area of perikaryon was located numerous small vacuoles, and sharply konturirovany periphery of hepatocytes were allocated intense saturation CHIC - positive fine-grained material. Marked changes were the result of active biosynthesis in hepatocytes and reserve deposits of glycogen in the cytoplasm. The volume of hepatocyte nuclei was 152,374,88 μm3that significantly exceeded the average volume of the nuclei of hepatocytes of the 2nd class and testified of their moderate polyploidization. On increasing synthetic activity in the nuclear apparatus of hepatitas testified also enriching their chromatin, the presence of one, rarely few, nucleoli srednia - 0,027. As a result, the protective action of synthetic melatonin in hepatocytes did not show manifestations of processes of lipid peroxidation in the form of destructive processes that cause the development of protein and lipid dystrophy. Bile ducts had a well-defined lumen. The mucosa of the bile duct was represented by a single layer of prismatic epithelial cells, mitotic activity in the nuclei of which were not found. Histochemical studies in the walls of blood vessels of the liver was not detected in the sediments chromotrope substances, demonstrating metachromasia. In the walls of blood vessels of the microcirculation of the body not marked signs of disorganization of connective elements. In the perivascular connective tissue, blood vessels of the portal system of the authority noted the presence of isolated lymphocytes. In moderately cravenplan sinusoidal capillaries were located isolated lymphocytes, macrophages.

The spleen. Spleen experimental mink had a weak figure follicular structure. Small follicles differed polymorphism with a predominance of compact form. The average size of lymph nodules was 105,81a 7.62.E. Germinative centers was 22,803,40.E. Cellular elements of the reactive centers of the nodules were presented swollen reticular cells, small blasts, medium-sized lymphocytes. Mitotic activity in the cells of the germinal centers of the nodules was poorly expressed and was observed only in single figures of mitosis. The main mass of lymphoid tissue nodules were small and medium-sized lymphocytes, most of which was concentrated at the periphery, close to the mantle zone of the nodule. The nuclei of these cells had a greater optical density and were enriched chromatin. Relatively narrow mantle zone of lymph nodules was presented sharply sdavlennym reticular fibers reticular cells, small and medium-sized lymphocytes. There has been a marked increase in the presence of small lymphocytes near thymusdependent periarterial zone knots. The sparsity of cellular elements in the marginal zone of the nodules was the result of intensive migration of lymphocytes in the red pulp of the body. Cellular elements of marginal zone of the lymph nodules were mostly loose reticular cells, among which were small lymphocytes. Adjacent marginal sinuses of OST is s, medium-sized lymphocytes, met macrophages and compact sparse clumps of plasmablasts. Found content increased megakaryocytes, mostly immature cell forms, distinguished by their small size and roundness of the boundaries of the cytoplasm and weak segmentation of the nucleus. Histochemical studies in the cytoplasm of the majority of megakaryocytes, reticular cells, macrophages was found an increased content of CHIC - positive material. These changes were indicative of a sufficient level of filtration of blood in the body and high activity of lymphoid-macrophage level cellular mechanism of manifestation of immune reactivity. This was also confirmed by the high level of activity of acid phosphatase in reticular cells, its germinative centers of knots and especially in small lymphocytes, located near periarterial zone and around ellipsoidal arterioles. Found no signs mulenga swelling and plasma soaking in the trabecular walls, Central arteries, ellipsoidal arterioles, combined weakly expressed CHIC - positive reaction and the absence of deposits chromotrope substances, developing metachroma the body, and, consequently, as a result of prolonged action components of the comprehensive drug containing synthetic melatonin and ksimedon, the spleen mink, patients with viral plasmocytosis, there is a change in the population composition of the cells of lymphoid tissue by increasing the content of thymusdependent lymphocytes. Slowing the process plasmocytomas transformation of cells of lymphoid tissue. The decrease in the size of lymph nodules in the spleen of experimental mink should be interpreted as a developmental delay immunomorphological changes caused by the invasion of virus in immunocompetent cells. Markedly reduced or even completely absent phenomenon disruption of components of connective tissue in the walls of blood vessels of the microcirculation. The experimental mink intensified processes thrombocytopoiesis. The development of viral plasmocytosis experimental mink acquired the character of a slow, subclinical infection, expressed the proliferation of reticular cells in the spleen.

The buds. Kidney experimental mink exposed to the integrated product, had a well-developed structure of the cortex and the medulla. The increase in volume of the glomeruli were presented again in endothelially mesangial cells were distinguished by the richness of chromatin granules. The observed decrease of the content of the cells juxtaglomerular and juxtamedullary cells. The nuclei of these cells were reduced in size and became intensely basophilic, reflecting the overall reduction process of biosynthesis of renin (vasoactive substances) in the body. Compensatory reaction to these processes should be considered to increase the amount and number mesangial cells, indicating the compensation of the deficit of the synthesis of vasoactive substances. Most epithelially convoluted tubule cells were intensely stained cytoplasm, without manifestations of protein, fatty dystrophy. The nucleus of epithelial cells of the proximal tubular organ system had an average volume 117,364,47 and contained a considerable number of elements in chromatin. A single layer of prismatic epithelium of the collecting tubules in module body was dominated by bright cells over the dark. The presence of small interstitially cells in the stroma of the pyramids body reflected moderate prostaglandin synthesis by these cells, which is probably offset by higher activity light alitalitton collective tubules. Around individual large vessels of the cortex of the kidney for some n is OK, testified to the weak intensity of the manifestations of the initial phase of viral plasmacytosis. Histochemical studies revealed that the greatest CHIC - positive reaction was shown by the basal membrane of the capillaries of the glomeruli, tubular organ system, as well as in the area of the brush border of epithelial cells of the proximal. And was not observed in contrast to the control not treated with drugs burrows deposition of mucopolysaccharides in the walls of blood vessels. Therefore, structural changes in the kidneys of patients burrows suggests that an infectious process is suspended or delayed at the stage of primary infection cycle, without activation of the autoimmune phase of the disease.

Stomach. The mucous membrane of the stomach experimental mink was characterized by integrity and foveolar pit epithelium, the cells of which there are provided a cylindrical shape. The cytoplasm of these cells was enriched CHIC - positive material, testifying to the intense development of a protective mucopolysaccharides. The oval nucleus of these cells due to increased synthesis MuCAP of polisaharidov was situated sharply basal and contained numerous intensively orasului glands, allocated large nuclei and were also saturated with elements of chromatin. In individual cells was found figures of mitosis. The content of the subepithelial cells in the apical part of the gastric mucosa was achieved 7,00,88. The marked cells are allocated hyperchromic core round or oval, located in the center of the cytoplasm, looking bright narrow bezel. Marked changes in the epithelial tissue of the gastric mucosa reflected moderate the regeneration of cells and the biosynthesis of these cells protective factor. Population Associacao in tubular glands was notable for its differentsirovannostj and multiplicity. In most nuclei of these cells were noted low content of the elements of chromatin, indicating that the completeness of cellular differentiation. The stromal elements of the gastric mucosa were represented by small lymphoid cells, histiocytes, fibroblasts, fibroblasts, undifferentiated cells. The vascular system of the body differed development of capillaries, arterioles, venules and lymphatic vessels and moderate content and absence of signs of disorganization items Catinat dehydrogenase in surface epithelial cells, the main and especially the parietal Associacao. Therefore, the condition of the gastric mucosa in experimental mink was characterized by the preservation of the cellular elements of the epithelium and the connective tissue of the body, high levels of synthetic and regenerative activity and production of digestive enzymes. It should be noted the absence of detected violations in the vascular wall, as well as plasmocytomas infiltration of elements of the stroma of the organ, often found in the mucosa of the control patients mink.

Thus, the detected structural changes in parenchymatous organs and the lining of the stomach experimental mink showed a significant reduction or even absence of manifestations of metabolic disorders arising from the development of viral plasmocytosis. We observed a sharp decrease in severity of plasmocytomas reaction; no or mild disorders of transcapillary exchange caused by disorganization of the vascular walls and deposition in them immune complexes; the absence of a generalized nature of the cellular responses of mesenchymal tissue, weakening metodicheskoe activity in cells of the lymphatic nodules in the spleen and in the and macrophages. Marked changes associated with the role of the tested drugs in the regulation of synthetic processes in the cells. The mechanism of action of Ximena, in our opinion, based on the inclusion of it as a kind of structural analogue of the pyrimidine base uracil in nucleoid and, consequently, the possible influence on the process of synthesis of mRNA species that created obstacles for the synthesis induced by virus, Aleutian mink disease early proteins (enzymes) or biosynthesis of proviral proteins. Resulting in a period of prolonged action of the drug provirus passed in vegetative form and did not cause damage to the cells and then induced second autoimmune phase of development of this disease. Melatonin helped to preserve the structures of cell membranes due to inhibition of processes of destruction lipoproteine complexes.

Morfologicheskie studies have been conducted in accordance with the methods [Rapoport J. L. Morphological basis of immunogenesis (immunomorphologic) - Architect. pathol., 1957, 2, S. 3-19; Fontain L. N. Immunological reactivity of lymphoid organs and runoff. HP: Medicine, 1967, 210 S.; Friedenstein A. J., Chertkov, I. L. Cellular basis of immunity. M: Medicinei, 1976, 264 S.; Petrov, R. C. Immunology. M.: Medicine, 1983, 367 S.; Avtandil gg, yabluchanskii N. And., Gubenko Century, the System stereometry in the study of the pathological process. M.: Medicine, 1981, 192 S.; Loyd H. , Gossrau R., Kibler So the Histochemistry of enzymes. Laboratory methods. M.: Mir, 1982, 272 S.].

Example 17. Sample tests of model compositions containing ksimedon and biodestruction polymer base (cellulose derivatives) technological additives in pig.

In pig-breeding complex of the fur farm "Kosakowski" tests of a prototype model compositions containing ksimedon (sample 13, PL. 1). In experiment 8 was used suckling pigs of large white breed (1 litter).

Just formed two groups of animals: experimental and control. Animals of both groups (experimental and control 4 little pigs each) were held together with a sow in an individual machine. The test drug is implanted Guinea pigs in a pasture tissue left groin using a needle And 28 on THE other 64-1-3177-77, the diameter of which is matched to the diameter of the granules of the drug. The injection needle and sterilized with 70% alcohol. The implantation was performed twice on the same dose of the drug: the experiment was conducted weighing piglets from the experimental and control groups. The difference in live weight gain experimental and control groups were not observed.

Example 18. Test preparations containing melatonin and ksimedon, pig.

In pig-breeding complex of the fur farm "Kosakowski" provedeni prototype testing of veterinary drug containing melatonin with ximedona. In the experiment had used 16 suckling piglets big trouble breed (2 litters).

Just formed two groups of animals: experimental and control. Animals of both groups (experimental and control) were held together with sows in individual stalls (2 machines). The test drug is implanted pigs in the subcutaneous tissue of the left groin with the help of needles And 28 on THE other 64-1-3177-77, the diameter of which is matched to the diameter of the granules of the drug. The injection needle and sterilized with 70% alcohol. The implantation was performed twice on the same dose of the drug: the first introduction made the piglets at the age of 12-14 days, the second at 36 days of experiment. In 1-, 19-, 36-, 54-the first day of the experiment were weighed piglets from the experimental and control groups. The weighing results are presented in table. 3.

Dynamics of changes in body weight of experimental and control animals of socata were transferred from sows in total corral on 54th day of the experiment. By the end of the experiment (54 days) body weight of Guinea pigs was higher than in control animals at 48%. Thus, the prolonged action of the drug containing synthetic melatonin and ksimedon, contributes to the activation of anabolic processes, leading to a significant increase in body weight suckling piglets and, consequently increasing productivity of animals.

Developed the drug can be recommended as an adaptogenic and stimulants, which increase nonspecific resistance of the organism of pigs in the postnatal period of development.

Thus, the results demonstrate the effectiveness of implantable veterinary preparations with prolonged action to improve safety, nonspecific resistance and productivity of farm animals.

Industrial applicability. Declare veterinary drugs can be used in fur farming, animal husbandry, veterinary medicine. The release of the first pilot batches scheduled for q IV 2002 - I 2003 square, LLC scientific-production enterprise "Vetta" at the all-Russian research veterinary inst the ula inventions

1. Veterinary implantable drug immunostimulating action, containing melatonin, biodestruction polymer base - fix-EE and plasticizer, characterized in that it further comprises ksimedon in the following ratio of components, wt.%:

Melatonin 5-25

Ksimedon 5-25

The propeller-EA (polymer) 89,95-35

The plasticizer of 0.05-15

2. Veterinary implantable drug immunostimulant activity on the basis of melatonin and biodestruction polymer, characterized in that as biodestruction polymer it contains water-soluble derivatives of cellulose and technological additives in the following ratio, wt.%:

Melatonin 10-50

Derivatives of cellulose 89,95-35

Technological additives of 0.05-15

3. Veterinary implantable drug under item 2, characterized in that as technological additives it contains water-soluble cellulose derivatives, preferably methylcellulose, sodium carboxymethyl cellulose.

4. Veterinary implantable drug on PP.2 and 3, characterized in that it further comprises ksimedon in the following ratio, wt.%:

Melatonin 5-25

Ksimedon 5-25

Proizvodi the

 

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