RU2614733C1 - Method of immunobiological status improvement in newborn piglets - Google Patents

Abstract

FIELD: agriculture.

SUBSTANCE: invention relates to the field of veterinary medicine and is intended to improve the immunobiological status of newborn piglets. The method comprises intramuscular administration of "Pirogenal" to pregnant sows at a dose of 0.08 mcg/kg body weight 60 days prior to farrowing as 5 injections every day, 40 days prior to farrowing as 5 injections at intervals of 1 day, 20 days prior to farrowing as 5 injections at intervals of 2 days, the general course is 15 injections during the prevention.

EFFECT: method of increasing immunobiological status for prevention of immune deficiency in piglets.

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Description

FIELD OF THE INVENTION

The invention relates to the field of veterinary medicine, in particular to methods for correcting the immunity of an organism of piglets and relates to a method for increasing the immunobiological status of newborn piglets by using the non-specific immunomodulating preparation “Pyrogenal” to sows during gestation.

State of the art

When studying patent and scientific and technical information, several methods were identified for increasing the immunobiological status of newborn piglets.

There is a method of increasing the resistance of the organism of newborn piglets using non-specific gamma-depthins (see Temporary instructions for the use of non-specific globulins in non-communicable diseases of young farm animals of early age // Veterinary legislation / Ed. General ed. By AD Tretyakov. M .: Kolos, 1973.Vol. 2.P. 82-83).

The disadvantage of this method is that gamma globulins do not contain antibodies against microflora circulating in a particular pigsty, and the effectiveness of their use to increase the safety of newborn piglets does not exceed 5%.

A known method of increasing the resistance of the body of newborn piglets using allogeneic immune serum of pigs (AISS) (see Allogeneic immune serum of pigs: Specifications 46-12-1452-83; Approved by the Ministry of Agriculture of the USSR on December 1983 )

The disadvantage of the proposed method is that (AISS) contains a small amount of specific antibodies per unit volume of the drug, and its implementation can lead to intoxication and suppression. In this case, the physiological peculiarity of the small intestine of newborn piglets to ineffective absorption of antibodies is not taken into account, while the natural resistance of the body of piglets increases by no more than 10%.

A known method of increasing the resistance of the body of newborn piglets, including the introduction of blood serum, characterized in that as a therapeutic and prophylactic drug, orally administered concentrated blood serum in a dose of 5 ml 2 times a day for the first 48 hours of life of piglets (see patent R. F. 2142805, IPC ⁶ A61K 35/14, publ. 12/20/1999).

The disadvantages of this method are that the use of blood serum can cause allergies, toxicosis. And the use of this method does not take into account the natural physiological status of the body. Despite this, the oral method of administration is inferior to the parenteral in the exact observance of the dosages and the effectiveness of the digestibility of the active substances.

A known method of immunobiochemical correction of homeostasis of piglets with the suiferrovit preparation, comprising inactivated normal serum with the addition of a complex of trace elements and vitamins (see Modern medicinal substances in veterinary medicine, Rostov-on-Don: Phoenix, 2001. P. 266).

However, the known method, with the complexity of the implementation, does not ensure the normalization of the immunobiological status in piglets and pregnant sows, acting on individual indicators, not taking into account the etiological factors of impaired immunometabolic processes and the physiological state of animals, as well as the estimated benefits for the mother's body, increase the potential risk to the fetus.

Closest to the technical solution is a method for the correction of immunobiochemical homeostasis of deep-sowing and lactating sows, sucking pigs, which consists in the use of intramuscular preparation metallosuccinate, which is administered to suckling pigs on the 2nd, 12th and 25th day after birth doses of 1.5 ml, 2.0 ml and 3.0 ml, respectively, to lactating sows according to the same scheme at a dose of 5.0 ml, and pregnant sows at a dose of 5.0 ml on the 80th and 97th day. (see patent R.F. 2393848 IPC A61K 31/00, A61K 31/194, A61K 31/295, A61K 33/24, A61K 31/26, A61K 31/30, A61K 31/34, A61K 35/12, A61P 3/02, published July 10, 2010).

Despite the likely positive effect, the indicated method for the correction of immunobiochemical homeostasis of deep-sowing and lactating sows, sucking pigs, has a number of significant disadvantages: laboriousness, difficulty in implementing and conducting, constant stress load on both the mother's body and offspring. Moreover, the method is aimed at eliminating the resulting fetal changes in the postpartum period with the already formed structural and functional changes in newborn animals. In addition, this method has increased financial costs due to the contained complex of multicomponent biologically active substances.

Disclosure of invention

The objective of the invention is to develop a method of increasing the immunobiological status of newborn piglets, aimed at more complete formation of the humoral and cellular link of the immune system in newborn animals, by intramuscular injection of a highly active non-specific broad-spectrum immunomodulator “Pyrogenal” to pregnant sows.

The technical result that can be achieved using the present invention is to prevent the immunodeficiency state of piglets in the fetal period by implementing an immunomodulating effect in the mother's body during the most stressful period (second half) of gestation. This technical result is achieved by intramuscular administration of a highly active non-specific broad-spectrum immunomodulator “Pyrogenal” to pregnant animals at a dose of 0.08 μg / kg body weight 60 days before the survey 5 injections every day, 40 days before delivery 5 injections with an interval of 1 day , 20 days before farrowing 5 injections with an interval of 2 days, a total course of 15 injections and is aimed at a more complete establishment of the immunobiological status in newborn animals.

The essence of the method is as follows: the use of pyrogenal in pregnant sows 60 days before the expected farrowing is due to its ability to activate macrophages, enhance phagocytosis (leading to an increase in antimicrobial resistance and accelerated antibody production) and the production of endogenous interferon, stimulate the production of interleukin-1 (IL-1 ), causing proliferation of a number of body cells (fibroblasts, endothelial cells, hematopoietic cells, etc.), interleukin-2 (IL-2), necessary for the growth of lymphocytes in (primarily T cells). Thus, macrophage-monocytic cells and the cytokines secreted by them are activated, the functional activity of both the cellular and the humoral unit in the mother-fetus functional system is enhanced.

It should be noted that the mother’s body, in critical periods of pregnancy, is in a state of physiological immunodeficiency associated with intensive formation and development of the fetus, preparation of the body for the production of colostrum and milk. For sows, this period occurs in the second half of gestation (70-100 days).

At the same time, thanks to the principle of interconnectedness and interdependence of homologous functional systems in the mother-fetus-newborn complex, it is possible to activate the own biological reactions of the newborn by acting on the mother's body when the fetus is born, in order to switch to a more advanced level of functioning immediately after birth.

It has been established that piglets are born at earlier stages of morphofunctional development compared to other farm animals, in a state of physiological immunodeficiency, which necessitates the use of immunostimulating drugs precisely in the fetal period of development, thereby allowing to obtain and grow more complete offspring.

Brief description of drawings and other materials

Table 1 gives a way to increase the immunobiological status of newborn piglets, shows the immunobiological status of pregnant sows of experimental and control groups.

Table 2 also shows the indicators of morphological and functional maturity of newborn piglets from experimental and control groups of sows.

Table 3 also reflects the indicators of the formation of the immunobiological status of piglets in the neonatal period obtained from experimental groups of sows.

Table 4 also shows the data on growth, development, and safety of piglets in the control and experimental groups.

The figure 1 also shows the dynamics of changes in body temperature in newborn piglets over the selected time interval.

The implementation of the invention

Examples of specific performance of the method of increasing the immunobiological status in newborn piglets.

Example 1

The individual minimum immunomodulating pyrogenic dose for sows was determined by intramuscular administration of the drug to repair pigs at the rate of 0.16, 0.08, 0.04 μg per 1 kg of body weight. The most optimal dosage for animals was 0.08 μg per 1 kg of body weight, which contributed to an increase in total body temperature to 0.5 ° C, which indicates the sufficiency of the optimal pyrogenic dose. One hour before the injection, temperature was measured twice at each sow at intervals of at least 30 minutes. Differences in temperature readings in the same animal did not exceed 0.1 ° C. The average temperature increase was up to 0.5 ° C.

To establish the positive effect of the use of Pyrogenal, 3 groups of pregnant sows of large white breed, 10 animals each were formed - two experimental and one control and piglets born from them, 10 animals each. The first, of which 0.08 mcg / kg m. the drug 60 days before farrowing, once a day until morning feeding with a total course of 15 injections. The second experimental group at a dose of 0.08 μg / kg m 60 days before the survey every day (5 injections), 40 days before delivery with an interval of 1 day (5 injections), 20 days before farrowing with an interval of 2 days (5 injections), a total course of 15 injections. The third group served as a control, which did not use the above drug. The duration of use was 30 days.

Example 2

It was found that when Pyrogenal was injected into experimental sows from the second half of pregnancy, their indices of natural resistance significantly increased, with normalization of the parameters of the cellular and humoral immunity, eliminating signs of an immunodeficiency observed from the second half of pregnancy (see table 1). However, the use of the proposed dosage and the frequency of administration of the drug for the experimental groups found their differences in the studied parameters.

So on the 90th day of pregnancy in the experimental groups of sows, compared with the 60th day, immunobiological indicators from the initial state stabilized. However, in the control group, the above values did not undergo significant changes from the initial immunodeficiency state and amounted to: the number of leukocytes 7.31 ± 0.21 × 10 ⁹ / l in the first experimental group, 8.97 ± 0.14 × 10 ⁹ / l - the 2nd experimental group, however, in the control group, the indicator did not exceed 6.57 ± 0.16 × 10 ⁹ / l. In sows of the experimental groups, the content of T-lymphocytes exceeded the control by 16.6%, 30.7%, and by B-lymphocytes by 27.4%, 56.6%.

Some of the indicators of natural resistance in the experimental groups also amounted to higher values, namely: the content of red blood cells in the first group was 4.88 × 10 ¹² / l, for the second - 6.78 × 10 ¹² / l; hemoglobin content - 62.6; 85.8 g / l, BASK - 46.49; 58.12%. Moreover, experimental sows from the 2nd experimental group had higher trends in these indicators in relation to the 1st group, and also significantly exceeded the control individuals: in erythrocytes - by 55.1%, hemoglobin - 37.5%, BASK - 56 ,5%.

The concentration of the main classes of immunoglobulins on the 90th day of pregnancy in the first and second groups was to an increasing degree and amounted to Ig A - 1.42 and 1.97 g / l, Ig G - 18.77 and 26.36 g / l, respectively .

With these significantly positive trends in the studied parameters, there is reason to argue that it favorably affects the decrease in the immunodeficiency effect of the organism of pregnant sows, but it should be noted that the highest positive effect from its use is observed in the 2nd experimental group of individuals.

Example 3

From table 2 it is seen that the injection of Pyrogenal in experimental sows from the second half of pregnancy had a more favorable effect on the physiological status and morphofunctional maturity of their offspring in the neonatal period. So, the appearance of a confident standing posture and sucking reflex in newborn piglets from sows of the experimental groups was realized earlier in the first group for 15.5 and 14.5 minutes, in the second for 18.0 and 24.1 minutes.

The average daily deviation of body temperature in the control group on the 1st day of life was 0.8 ° C and 1.0 ° C higher than in the experimental groups of piglets, on the 2nd day at 0.9 ° C and 1.2 ° C, and on the third day at 2.0 ° C and 2.3 ° C, respectively.

From an analysis of the data obtained, it was found that in piglets from the control group at birth, body temperature was lower than in other peers, and the average body temperature for the first day of the newborn was reduced by 2, 4, 6, 12, 24 hours after birth up to 36.24 ± 0.03; 36.38 ± 0.09; 36.34 ± 0.02; 36.58 ± 0.03; 36.67 ± 0.04 ° C. The average body temperature in the control group of newborns at birth was 36.27 ± 0.03 ° C in relation to 37.24 ± 0.03 ° C in experimental pigs, which indicates dynamically reduced values of the formation of body temperature over the selected time interval in analyzed offspring relative to peers from experimental groups.

By live weight among newborn piglets, for the first day of life, differences were established. The distribution rank in the control group according to body weight at birth was the largest from the minimum value - 864 g, to the maximum - 1544 g, and after the first 24 hours of the newborn, the maximum value was 1528 g and the minimum was 836 g. The range of variation in body weight of these animals at birth amounted to 680 g, and after 24 hours - 664 g, which indicates an increase in the ratio of the initial value to the value for the time interval.

With all this, transient decrease in body weight during the first day of life was observed in individuals from the control group. At the same time, the experimental groups of piglets had higher trends in these indicators relative to the analyzed group, while among these animals transient decrease in body weight was not recorded, but positive dynamics was observed over a specified time interval. The identified trend, expressed in superiority in mass, continued after 72 hours of neonatality.

, где M₂ - масса тела животного через 24 часа после рождения, а M₁ - масса тела животного при рождении. Данный коэффициент составил для первой группы поросят К₁=1,09±0,08, для второй К₂=1,59±0,02 и для третьей К₃=1,12±0,04, что находилось в пределах физиологических значений. В то же время у контрольной группы данный коэффициент был равен К_конт.=0,84±0,01, который принимал значения ниже физиологического уровня равного 0,99-1,05. Новорожденные с низким коэффициентом катаболизма при неблагоприятных воздействиях внешней среды предрасположены к заболеваниям.The level of morphofunctional maturity of newborn piglets was determined according to the developed method with the calculation of the coefficient of catabolism (see the method of I.S. Egoshin - 1984) by the formula

where M ₂ is the body weight of the animal 24 hours after birth, and M ₁ is the body weight of the animal at birth. This coefficient was for the first group of piglets K ₁ = 1.09 ± 0.08, for the second K ₂ = 1.59 ± 0.02 and for the third K ₃ = 1.12 ± 0.04, which was in the range of physiological values . At the same time, in the control group, this coefficient was equal to K _cont. = 0.84 ± 0.01, which took values below the physiological level equal to 0.99-1.05. Newborns with a low coefficient of catabolism under adverse environmental influences are predisposed to diseases.

Example 4

The main and most significant effect of the use of Pyrogenal was the establishment of indicators of the immunobiological status of piglets from experimental groups of sows in relation to the control. So for the neonatal period, the resulting offspring had the following differences (see table 3).

It was found that on the 10th day after birth, the indicators of immunobiological potential in piglets from the second group of sows were at a fairly high level. This was expressed in the fact that in the quantitative composition of T- and B-lymphocytes this group exceeded the control individuals reliably in T-lymphocytes by 51.1% and 53.9% in B-lymphocytes. This condition can be characterized as a pronounced process of leukopoiesis in the second group. Despite this, the other two groups of piglets from experimental sows also had a higher content of T-lymphocytes by 15.3%, and by B-lymphocytes by 23.8%.

A stimulating effect on hematopoiesis was also revealed - the number of red blood cells in the piglets of the experimental groups on the 10th day was higher in the 1st group by 1.18 × 10 ¹² / l, in the 2nd by 1.66 × 10 ¹² / l, and the hemoglobin content exceeded 13.79 and 18.66 g / l, respectively.

Indicators of phagocytic activity of neutrophils (FAN), bactericidal (BASK) and lysozyme (LASK) activity of blood serum in piglets indicate that the level of non-specific humoral protection in animals from the experimental groups was more pronounced. So FAN for the first group was at the level of 37.25%, BASK - 31.47%, and LASK - 34.21%, for the second FAN - 41.62%, BASK - 39.30% and LASK - 43, 46% However, in piglets of the control group, these values were FAN - 31.74%, BASK - 27.61% and LASK - 30.08%.

The concentration indices of the main classes of immunoglobulins in piglets from the experimental groups of sows also exceeded the Ig A control by 22.2% and 55.4%; Ig G by 47.1% and 51.2%, and Ig M by 40.9%, 55.6% for the analyzed groups.

Example 5

To assess the effectiveness of the tested method, experimental pigs were monitored for 2 months after birth according to the growth, development and safety data, which are presented (see table. 4).

It was found that for the mentioned observation period, piglets from sows of the experimental groups in absolute growth, average daily gain significantly exceeded 50.8% and 81.1%, the control group. Moreover, the safety in these groups was 100%, the incidence rate was 19.7%. While in the control group, the safety was 70.2%, the incidence was 44.8%, and mortality was 29.8%.

Thus, a change in the formation of the main immunobiological and morphofunctional indicators in the neonatal period suggests that the most plastic adaptation of newborn piglets from the 2nd experimental group in relation to the experimental and control ones is analyzed, which helps to create a higher level of adaptive, metabolic potential and immunobiological status in born offspring. Given the above data, the use of the proposed method can serve as the basis for the prevention of postnatal complications.

In accordance with the priority provisions of the Soviet physiologist P.K. Anokhin (Anokhin PK. The key questions of the theory of functional systems. - M., 1980) any organism is considered as a functional system, the main principle of which is self-regulation. The principle of self-regulation is that any deviation of the result of the functional system from the level that determines the normal (natural) metabolism or other aspects of the normal functioning of the body based on feedback immediately selectively mobilizes the various mechanisms of the system to return this result to the optimal metabolic level. However, under certain environmental influences, the system does not return to the optimal level, as a result of which metabolic disturbance leads to various pathological conditions.

According to the theory of systemogenesis, in the antenatal period, selective accelerated development of those structures occurs that at the time of birth should ensure the existence of the newborn in extrauterine conditions.

Despite the complexity of the regulatory system, all central metabolic pathways have now been almost completely established, but the mechanisms of their regulation are still unexplored. Thus, the key to solving the problem of creating highly effective medicines of any pharmacotherapeutic group is to unravel the regulation mechanism in the functional system “mother-fetus-newborn”.

From the study, we can conclude that the invention has the following advantages in relation to known developments:

1. The proposed method has a preventive focus on the immunodeficiency state in newborn piglets, carried out in the fetal period of development.

2. It has less complexity in the application, making it simple and affordable for technical implementation in any agricultural enterprise

3. Eliminates the need for invasive and stressful manipulations in newborn piglets in the early stages of postnatal development, which increases their sensitivity, with possible complications

Claims (1)

A method for increasing the immunobiological status of newborn piglets, including intramuscular administration of a highly active non-specific broad-spectrum immunomodulator to pregnant sows, characterized in that Pyrogenal is used as an immunomodulating drug in a dose of 0.08 μg / kg of body weight to pregnant sows 60 days before 5 injections every day, 40 days before delivery 5 injections with an interval of 1 day, 20 days before farrowing 5 injections with an interval of 2 days, a total course of 15 injections.

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