RU2428992C1 - Preparation for correction of stress states in agricultural animals - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: medication includes lithium oxybate, sodium selenite, ascorbic acid and water for injections with the following component ratio, wt %: lithium oxybate - 4.0-7.0, sodium selenite - 0.2-0.5, ascorbic acid - 3.0-12-0, water for injections - the remaining part. ^ EFFECT: medication possesses expressed nootropic activity and immunostimulating action, is convenient to introduce. ^ 1 dwg, 4 tbl, 6 ex

Description

FIELD OF THE INVENTION

The invention relates to veterinary pharmacy, in particular to preparations for the correction of stress conditions in farm animals with antioxidant and immunostimulating properties.

State of the art

A known drug according to the method of prevention and correction of transport stress in cattle, the essence of which involves feeding animals 3-7 days before they are transported at a dose of 125-257 mg / kg body weight per day of salt composition, including, wt.%:

Sodium chloride 7.4-9.8 Sodium carbonate 0.4-0.8 Calcium carbonate 8.0-11.0 Magnesium carbonate 1.0-1.4 Ascorbic acid 0.1-0.3 Glucose 18.0-22.0

The tool is given in the form of salt in a mixture with concentrated feed (see US Pat. RU No. 2033048, class A01K 67/02, A61K 33/00, publ. 04/20/1995).

The disadvantage of this drug is a low antioxidant and anti-stress effect, insufficient increase in the overall resistance of the body.

A known drug according to the method of prevention and correction of transport stress in cattle, which involves feeding animals 4-5 days before transporting them at a dose of 210-230 mg / kg live weight per day of the supplement, including, wt.%:

Bischofite 78.75-80.85 Vitamin C 0.15-0.25 Glucose 19.0-21.0

The additive is fed in a mixture with concentrated feed (see US Pat. RU No. 2153802, class A01K 67/02, A61K 33/00, publ. 10.08.2000).

The disadvantage of this drug is the lack of a specific nootropic component in its composition and, due to this, a low anti-stress effect.

The closest in technical essence and the achieved positive effect and adopted by the authors for the prototype is a drug with nootropic activity (options).

The drug in the form of an aqueous solution contains the following components in wt.%:

Dimephosphone 15.0-30.0 Lithium carbonate 0.5-5.0 Lemon acid 3.0-4.0 Deionized water up to 100

The drug in the form of a syrup has the following composition in wt.%:

Dimephosphone 3.0-5.0 Lithium carbonate 1.0-1.2 Lemon acid 4.0-5.0 Sugar syrup 89.0-92.0

(see Pat. RU 2341973, class A23K 1/175, publ. 12/27/2008).

The disadvantage of this drug is a lack of antioxidant effect, a low effect of increasing the overall resistance of the body.

Disclosure of invention

The objective of the invention is to develop a drug for the correction of stress conditions in farm animals, which has a pronounced anti-stress, antioxidant effect, high efficiency in the presence of an immunostimulating effect.

The technical result that can be achieved using the present invention is reduced to anti-stress and antioxidant effects, increasing the body's resistance, prevention and treatment of technological stress.

The technical result is achieved using a drug for the correction of stress conditions in farm animals, including lithium oxybate, ascorbic acid and water for injection, while the drug additionally contains sodium selenite in the following ratio of components in wt.%:

Lithium oxybate 4.0-7.0 Sodium Selenite 0.2-0.5 Ascorbic acid 3.0-12.0 Water for injections rest

The essence of the preparation for the correction of stress conditions in farm animals is as follows: starting materials in wt.%, Namely lithium oxybate 4.0-7.0, sodium selenite 0.2-0.5, ascorbic acid 3.0-12 , 0, water for injection - the rest is mixed under aseptic conditions and packaged.

One of the reasons for the incomplete manifestation of the genetic potential potential of farm animals should be considered stress loads arising from the need for various veterinary measures: transportation, formation of production groups, numbering, haulage, weighing, veterinary processing, etc., which leads to losses of more than 20% of the expected productivity and lowering economic indicators of livestock production (see Salo A., Kinyabulatova R. // Dairy and beef cattle breeding. - 2009. - No. 2. - S.19-21).

The pharmacological effect of the drug is that with the use of lithium, a normalizing effect on the cell membrane and the course of biological processes in the cell occurs, while lithium ions act as mediators of the nervous and hormonal regulation of individual organs and entire systems, participate in immune, homeostatic and adaptive reactions of the whole organism, have a psychotropic property (see Lazareva D.N., Alekhin E.K. Immunity stimulants. - M. - 1984. - P.198-199 .; Mkhitaryan V.G., Yeritsyan L.N. Journal experimentally and clinical medicine -. 1981. - №2 -. S.121-125).

One of the most important pharmacological properties of lithium salts is their ability to increase the population of polymorphonuclear leukocytes (see Yavorkovsky L.L. Problems of Hematology. - 1982. - No. 11. - P.50-56; Gregson MW Canad. J. Med. Technol. - 1979. - Vol. - 41. - P.158-164; Murphy DL, Goldsmith FK, Bunney WE Amer. J. Psychiat. - 1971. - Vol. - 127. - P.1559-1561). Selectively accumulating in the thymus gland, lithium preparations clearly affect T-lymphocytes, while their killer function is noticeably enhanced (see Perez Cruet J Waite, Mallya A., Khaiawali AM Lithium Contraversies and Unresolved Issues. - Amsterdam. - 1979. - P .881-894).

Recently, a special place in a series of substances that have both antioxidant and adaptogenic properties, researchers give compounds of selenium (See. Tsogoev F.N. Veterinarian. - 2009. - No. 5. - P.41-42).

When studying the microelement status of animals in the Stavropol Territory, a significant deficiency in the blood of such vital trace elements as selenium and copper, directly affecting the homeostasis of the body and the course of redox reactions in it, was revealed (see.Kireyev I.V. Pharmaco-toxicological properties of extrasylene and its application in veterinary medicine. Author's abstract of thesis for the degree of Candidate of Biological Sciences. - Krasnodar. - 2009. - 22 p.).

Oxidative stress, which is based on a violation of the processes of free radical oxidation, is currently considered as one of the leading pathogenetic mechanisms of the occurrence of diseases of various etiologies (see Zenkov N.K. Oxidative stress: biochemical and pathophysiological aspects. - M.: Science / Pedagogy, 2001 - 343 p.). Selenium is an indispensable element for the glutathione-glutathione peroxidase defense system against oxidative stress (see Karmoliev R.Kh. Veterinary Medicine. - 2005. - No. 4. - P.42-47).

Selenium takes part in the functioning of the antioxidant system due to the fact that it is composed of four selenium-dependent glutathione peroxidases, which differ in the number of selenium atoms, dislocation in the body, structure and specificity of functions, while classical glutathione peroxidase protects cells from oxidative stress by restoring any type of hydroperoxides ( see Liboska J. Prax. Vet. - 1984. - Vol.32. - No. 4/6. - P.231-236).

Ascorbic acid is an effective and affordable antioxidant, due to the presence of two conjugated double bonds it has the ability to be reversibly oxidized, and the main point in its mechanism of action is the possibility of conversion to dehydroascorbic acid, which in turn led to the ability to intercept singlet oxygen, a superoxide anion radical, hydrogen peroxide and hydroxyl radical (see. Georgievsky V.I. Fizilogiya farm animals. - M .: Agropromizdat, 1990. - 512 p .; Sokolov V.D., Rabinovich M.I., Gorsh G.I. et al. Pharmacology. - M .: Kolos, 1997. - 543 p .; Usha B.V., Belyakov I.M., Pushkarev R.P. Clinical diagnosis of internal non-communicable animal diseases. - M. : KolosS, 2003 .-- 487 p.).

The implementation of the invention

Examples of specific performance of obtaining and testing the drug for the correction of stress conditions in farm animals.

Example 1

The drug for the correction of stress conditions in farm animals is prepared by mixing the components under aseptic conditions and dissolving in water for injection in the following ratio of components in wt.%:

Lithium oxybate 3.0 Sodium Selenite 0.1 Ascorbic acid 1,0 Water for injections rest

The obtained preparation, when tested under simulated stress conditions in rabbits, showed a relatively low decrease in TBA-active products in the blood - by 2.27%, catalase activity increased by 4.71%, glutathione peroxidase activity by 7.18%, and the content of reduced glutathione - by 0.42%, glucose - by 0.79%, a decrease in live weight over an average of 10 days amounted to 214 g.

Example 2

Carried out analogously to example 1, but take the following ratio of components in wt.%:

Lithium oxybate 4.0 Sodium Selenite 0.2 Ascorbic acid 3.0 Water for injections rest

The resulting preparation, when tested under simulated stress conditions, showed pronounced positive dynamics relative to the activity of antioxidant enzyme enzymes; Thus, the activity of catalase increased by 7.34%, and the activity of glutathione peroxidase - by 11.02%, the amount of reduced glutathione increased by 1.92%, and the level of glucose in the blood increased by 0.39%. The decrease in live weight over the same period was 92 g.

Example 3

Carried out analogously to example 1, but take the following ratio of components in wt.%:

Lithium oxybate 5,0 Sodium Selenite 0.3 Ascorbic acid 6.0 Water for injections rest

The resulting preparation, when tested under conditions of simulated stress, showed a tendency to stabilize biochemical parameters. The level of selenium in the blood increased to 10.23 μg%, which is the physiological norm. The level of TBA-active products decreased by 13.24%, catalase activity increased by 9.06%, glutathione peroxidase - by 11.58%, glucose level increased by 0.71%, reduced glutathione - by 3.12%. The loss of live weight over the same period was 76 g.

Example 4

Carried out analogously to example 1, but take the following ratio of components in wt.%:

Lithium oxybate 6.0 Sodium Selenite 0.4 Ascorbic acid 9.0 Water for injections rest

The resulting preparation, when tested under simulated stress conditions, showed a slight decrease in gain in live weight - by 62 g. The level of TBA-active products decreased by 14.20%. The activity of catalase and glutathione peroxidase increased by 11.33% and 15.42%, respectively. Blood glucose levels increased by 0.95%, and the amount of reduced glutathione increased by 3.64%.

Example 5

Carried out analogously to example 1, but take the following ratio of components in wt.%:

Lithium oxybate 7.0 Sodium Selenite 0.5 Ascorbic acid 12.0 Water for injections rest

The resulting preparation, when tested under simulated stress conditions, showed a 71% decrease in gain in live weight. The level of TBA-active products decreased by 10.26%. The activity of catalase and glutathione peroxidase increased by 9.92% and 12.34%, respectively. Blood glucose levels increased by 0.78%, and the amount of reduced glutathione increased by 2.83%.

Example 6

Carried out analogously to example 1, but take the following ratio of components in wt.%:

Lithium oxybate 8.0 Sodium Selenite 0.6 Ascorbic acid 12.0 Water for injections rest

The obtained preparation, when tested under conditions of simulated stress, showed a significant decrease in live weight — by 167 g. The concentration of TBA-active products decreased by 3.24%. The levels of reduced glutathione and glucose decreased by 0.39% and 0.14%, respectively. The activity of catalase and glutathione peroxidase increased by 5.22% and 9.51%, respectively. At the same time, the level of total bilirubin increased by 2.12%, AsAt and AlAt by 3.42% and 1.81%, respectively, which may act as evidence of a toxic effect from the use of the drug in this ratio of components.

Thus, the most optimal examples are 2, 3, 4, and 5, since as a result of the use of the drug it is clearly seen that when analyzing the dynamics of the live weight of rabbits, it decreased slightly (from 62 g to 76 g), which also increased the activity of enzymes from the enzymatic link of the antioxidant defense system of the body, in particular the activity of glutathione peroxidase (from 11.02% to 15.42%) and catalase (from 7.34% to 11.33%), which, in turn, led to a decrease in the concentration of TBA- active products - by-products of free radical reactions - and p edupredilo the development of oxidative stress.

To evaluate the drug for the correction of stress conditions in farm animals for acute toxicity, the following ratio of components in wt.% Was taken:

Lithium oxybate 6.0 Sodium Selenite 0.4 Ascorbic acid 9.0 Water for injections rest

Toxicological studies were performed on white laboratory mice and laboratory rats, which made it possible to determine lethal doses and classify the drug according to GOST and class 3 (Table 1, graph).

Table 1 Acute toxicity of the drug for the correction of stress in farm animals Animal species Toxicity parameters SLD ₅₀ MTD LD ₁₆ LD ₅₀ LD ₈₄ LD ₁₀₀ White mice fifty 91.6 170 238.3 300 1.83 White rats 63,2 105.3 176.9 275.9 379.2 2.13

The effectiveness of the drug was studied on sheep aged 1.4-1.7 months under conditions of combined stress. Prevention of technological stress was carried out during the haircut. This consisted in the fact that before shearing, the sheep were divided into two groups (n = 10). The animals of the first group were injected with a dose of 3.9 mg / kg of the active substance 24 hours before the start of the haircut, the second group did not receive the drug and served as a control. The experimental sheep immediately after shearing were placed in a restricted paddock, where the area per sheep was 1.3 m ² , and this was a simulated component of a stressful situation. Animals in the pen were kept for five days, while feeding and drinking were not limited. 4 hours after shearing, the sheep of the experimental group were similarly injected with the drug, the introduction was repeated after three days. Blood was taken before administration, 4 hours after the haircut (before the second injection) and after 5 days after the haircut and 10 days after the haircut. Weighing was carried out on an electronic balance at similar times with blood sampling.

When analyzing the results of the studies, a decrease in the number of red blood cells was found in both groups: in the experimental - by 2.5%, in the control - by 13.4% (Table 2). A similar dynamics was observed in relation to the level of hemoglobin, which decreased in the first group by 3.6%, and in the second - by 7.0%. The level of total protein decreased in the sheep of the experimental group by 0.27%, in the control - by 1.8%. The level of total calcium in the blood decreased in the first and second groups by 2.27% and 1.56%, respectively, and inorganic phosphorus - by 1.65 and 6.30%, respectively. Significantly changed the concentration of selenium in the blood, which in the first group increased by 7.5 times, and in the control slightly decreased and was 6 times lower than the physiological norm. The level of vitamin C in the blood serum of sheep who were injected with the drug increased by 39%, while in the control it decreased by 14.5%.

Significant changes have occurred in relation to indicators that are significant for the functioning of the antioxidant defense of the body, which is one of the first in the body to respond in response to a stress reaction. So, the level of reduced glutathione in the experimental group increased by 8.8%, and in the control decreased by 18.75%. The activity of catalase and peroxidase in the first group increased by 11.05% and 19.21%, respectively, and in the second decreased by 13.45% and 19.21%. Glutathione peroxidase activity increased in the first group by 22.1%, and in the second decreased by 9.2%. The concentration of diene conjugates in the blood of sheep from the first group remained unchanged after 10 days, and in the blood of control sheep increased by 15.9%. The level of malondialdehyde in the first group decreased by 0.43%, and in the second group increased by 28.12%.

One of the most critical indicators during exposure to stress factors is the dynamics of live weight. When analyzing the results of weighing sheep, it was found that over the 10 days of the experiment, the animals of the first group lost an average of 0.87 kg, and the animals of the second group - 2.65 kg (Table 4).

Table 4 Dynamics of live weight of sheep, kg Group Before introduction 4 hours after the haircut 5 days after the haircut 10 days after the haircut one 38.51 ± 2.92 38.56 ± 2.93 37.93 ± 2.74 37.64 ± 2.82 2 36.92 ± 2.34 36.84 ± 2.37 34.18 ± 2.42 34.27 ± 2.61

The advantages of the proposed drug is that it contains natural antioxidants and lithium oxybate in the complex - a compound with pronounced nootropic activity and an immunostimulating effect. Along with a specific anti-stress effect, it has the ability to normalize selenium metabolism, which contributes to an increase in the activity of the enzymatic link of the antioxidant defense of the body and makes it possible to treat and prevent oxidative stress in animals.

The invention in comparison with the prototype and other technical solutions has the following technical advantages:

- increased anti-stress effect;

- increase antioxidant action;

- increase in biological activity;

- ease of administration and dosage.

Claims (1)

A preparation for the correction of stress conditions in farm animals, characterized in that it includes lithium oxybate, sodium selenite, ascorbic acid and water for injection in the following ratio of components, wt.%:
Lithium oxybate 4.0-7.0 Sodium Selenite 0.2-0.5 Ascorbic acid 3.0-12.0 Water for injections rest

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