RU2776671C2 - Use of clathrate complex of 20-hydroxyecdysone with arabinogalactan for normalization of metabolism, increase in non-specific resistance, growth and development of animals - Google Patents

Abstract

FIELD: pharmacology; veterinary medicine.

SUBSTANCE: invention relates to the field of pharmacology and veterinary medicine, and it is aimed to correcting action of animal growth and development. The use of a clathrate complex containing 20-hydroxyecdysone and arabinogalactan is described for an increase in non-specific resistance, anti-oxidant status of an organism, growth and development of animals.

EFFECT: effective increase in non-specific resistance, antioxidant status of an organism, growth and development of animals at the same time.

1 cl, 9 tbl, 2 ex

Description

Application of clathrate complex of 20-hydroxyecdysone with arabinogalactan to normalize metabolism, increase resistance, antioxidant status of the body, growth and development of animals

The invention relates to the field of veterinary medicine and can be used in pharmacology, medicine and animal husbandry for oral administration and inclusion in the diets of animals and poultry in order to normalize metabolism, increase their nonspecific resistance, growth and development.

One of the innovative approaches to the creation of a new generation of specialized products can be the use of phytopreparations as “micro-ingredients” in their composition, which increase the resistance of the body and ensure the normal functioning of all its organs and systems. Of particular interest in this regard are plant sources of phytoecdysteroids - polyhydroxylated sterols that do not have a hormonal effect on mammals and have low toxicity. Phytoecdysteroids are characterized by pleiotropy (multiplicity) of biological action. One of the most widely studied phytoecdysteroids is 20-hydroxyecdysone. 20-hydroxyecdysone is found in some plant species and also in food spinach. The multiplicity of physiological effects in combination with the low toxicity of 20-hydroxyecdysone makes it possible to use it (mainly as an individual compound) as part of biologically active additives (BAA) to food and feed. In recent years, there has been great progress in the study of phytoecdysteroids, their corrective participation in the processes of protein, carbohydrate and lipid metabolism is being intensively studied.

However, there are still little studied issues related to studies aimed at increasing solubility, improving bioavailability, reducing the doses used, including in the diets of animals and birds, and prolonging the action of 20-hydroxyecdysterone. Modern trends in the development of new drugs are based on the creation of nanostructured compositions with improved characteristics. The creation of nanostructured compositions involves the synthesis of clathrate complexes of β-cyclodextrin, arabinogalactan, and gum arabic with 20-hydroxyecdysterone. In this regard, the creation of a soluble, bioavailable nanosized form of 20-hydroxyecdysone and the study of its corrective effect on the processes of protein, carbohydrate and lipid metabolism, the physiological state of animals, the resistance of their body, growth and development is relevant.

One of the most promising areas in the development of such tools is mechanochemistry. The creation of new dosage forms by mechanochemical activation is based on the creation of a complex by combining carriers, for example, arabinogalactan with 20-hydroxyecdysterone.

Known clathrate complex of arabinogalactan or gum arabic with 20-hydroxyecdysone, method for its preparation (options), pharmaceutical composition and drug with antidiabetic effect /Patent for the invention of the Russian Federation 2572334, publ. 01/10/2016/.

The technical problem to be solved by the present invention is to expand the arsenal of tools that simultaneously have the following characteristics:

- exhibit a corrective normalizing effect on metabolism, the physiological state of animals;

- improve resistance, antioxidant status of the organism of animals;

- increases the rate of growth and development of animals;

- retains stability during storage and, therefore, has improved physico-chemical properties.

The stated technical problem is achieved by using a clathrate complex consisting of 20-hydroxyecdysone with arabinogalactan, with the following content:

20-hydroxyecdysone 10 wt.% and arabinogalactan the rest, as a means of normalizing metabolism, increasing nonspecific resistance, antioxidant status of the body, growth and development of animals.

There is no information in the literature on the use of a clathrate complex consisting of 20-hydroxyecdysone with arabinogalactan, with its content of 10 wt.% and arabinogalactan the rest, as a means for normalizing metabolism, increasing resistance, antioxidant status of the organism, growth and development of animals.

New in the proposed invention is that, as a means for normalizing metabolism, increasing resistance, antioxidant status of the body, growth and development, a clathrate complex consisting of 20-hydroxyecdysone with arabinogalactan with a total content of 10 wt.% and arabinogalactan - the rest can be used. For a person skilled in the art, these properties do not explicitly follow from the prior art.

To solve the technical problem, the present invention proposes a clathrate complex of 20-hydroxyecdysone with arabinogalactan, which ensures the normalization of metabolism, increased resistance, antioxidant status of the body, growth and development.

Statistical processing of the research results was carried out using parametric and non-parametric methods. Differences between groups were considered statistically significant at p<0.10-0.05.

The proposed Complex is 20-hydroxyecdysone with arabinogalactan.

The essence of the invention is illustrated by examples of a specific implementation, in which:

clathrate complex consisting of 20-hydroxyecdysone with arabinogalactan with a total content of 10 wt. % and arabinogalactan - the rest obtained by the standard method / RF Patent No. 2572334, 2015; Fedorova A.V., Erimbetov K.T., Bondarenko E.V., Goncharova A.Ya., Frog E.S. / Development of a nanosized form of 20-hydroxyecdysone// EXPERIMENTAL AND CLINICAL PHARMACOLOGY. 2018 Volume 81 Appendix p. 254].

EXAMPLE 1. Metabolism-correcting clathrate complex of 20-hydroxyecdysone with arabinogalactan was evaluated in experiments on Wistar rats in a streptozotocin model of diabetes mellitus.

When developing the research methodology, the recommendations set out in the Guidelines for conducting preclinical studies of drugs and the generally accepted approach to the formation of a streptozotocin model of diabetes mellitus in Wistar rats were taken into account [Guidelines for conducting preclinical studies of drugs. Part one (under the general editorship of A.N. Mironov). M.: Grif and K, 2012.- 944 p.].

The experiment was carried out on 32 male Wistar rats weighing 160-180 g. Rats were kept in accordance with the requirements for the maintenance of laboratory animals (Order of the Ministry of Health of the Russian Federation No. 708n) on standard certified feeds under controlled conditions at a temperature of 18-20 ˚C, air humidity of 30-70% and natural light. All experimental work with laboratory animals was performed in accordance with generally accepted standards for the treatment of animals, based on standard operating procedures that comply with the rules of the European Convention for the Protection of Vertebrate Animals used for Scientific Purposes.

Prior to induction of the streptozotocin model of diabetes mellitus, body weight and baseline blood glucose levels were determined in all rats. The level of glucose in venous blood (from the tail vein) was determined using an Accu-Chek Performa Nano glucometer (Germany). The research material is venous blood.

An animal model of diabetes mellitus was induced by combined administration of streptozotocin and nicotinamide to adult rats. Nicotinamide was administered to rats (230 mg/kg, ip) 15 min before streptozotocin (65 mg/kg, iv). At the same time, moderate and stable non-fasting hyperglycemia developed without a significant change in the level of insulin in the blood plasma. Nicotinamide showed a protective effect, reducing the cytotoxic effect of streptozotocin, which led to moderate damage to pancreatic β-cells. Subsequently, animals with a blood glucose level exceeding 10 mmol/l, that is, rats with developed diabetes mellitus, were selected for the experiment, and 3 groups were formed from among them.

The animals were divided into 4 groups of 8 individuals each. The rats of each group were administered the appropriate preparations daily for 15 days according to the scheme:

Group 1 - Control (suspension of 1% starch gel);

group 2 - Metformin at a dose of 200 mg / kg;

Group 3 - The proposed complex at a dose of 1.0 mg/kg.

Group 4 - The proposed complex at a dose of 10.0 mg/kg.

The introduction of drugs was carried out 3 days after the introduction of streptozotocin and nicotinamide. The reference drug was Metformin. The proposed complex and reference drug were administered intragastrically as a suspension in 1% starch gel in a volume of 2 ml. Glucose levels were measured with an Accu-Chek Performa Nano glucometer (Germany) in venous blood obtained from the tail vein of rats on days 7 and 15 of the experiment.

Massometry was carried out at the beginning and at the end of the experiment, changes in body weight were assessed.

On the 15th day, the animals were taken out of the experiment, an autopsy was performed, blood was taken, serum was isolated and frozen for further studies on the content of total cholesterol, cholesterol - high density lipoproteins (HDL cholesterol), cholesterol - low density lipoproteins (LDL cholesterol), cholesterol - lipoproteins very low density (VLDL cholesterol), triglycerides, urea, creatinine, determination of the activity of alkaline phosphatase (EC 3.1.3.1), creatine phosphokinase (EC 2.7.3.2), lactate dehydrogenase (EC 1.1.1.27), alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (CF 2.6.1.1). Biochemical parameters of blood serum were determined using kits produced by the Unimed company on an automatic biochemical analyzer ARD-300. Based on the obtained data on the lipid profile of blood serum, the atherogenic coefficient (CA) was calculated using the following formula:

CA = (LDL-C + VLDL-C) / HDL-C (1)

As a result of the study, it was found that in terms of changes in body weight of rats, the compared groups did not differ statistically significantly. The introduction of the proposed complex at doses of 1.0 and 10.0 mg/kg compared with the control and the reference drug Metformin did not affect the change in body weight of rats with a model of diabetes mellitus (Table 1).

Table 1 - Change in body weight of rats with a model of diabetes mellitus after 15 days of administration of the clathrate complex of 20-hydroxyecdysone with arabinogalactan and the reference drug metformin

No. Groups Number of animals original body weight,
M±m Body weight final, М±m Relative mass change
body, %, М±m one Control eight 152.50±3.56 171.13±8.85 12.08±4.78% 2 Metformin eight 154.50±3.69 169.50±7.33 10.25±5.61% 3 Suggested Complex, 1.0 mg/kg eight 151.75±2.86 174.25±3.87 15.27±4.05% four Proposed Complex, 10.0 mg/kg eight 154.50±4.31 182.38±9.79 18.05±5.56%

The results of the studies indicate that intragastric administration of the proposed complex at doses of 1 and 10 mg/kg contributes to the normalization of blood glucose levels in Wistar rats by the 15th day of the experiment. The introduction of the reference drug Metformin does not have a statistically significant effect: the glucose level does not statistically significantly differ from that of the rats in the control group (Table 2).

Table 2 - Change in blood glucose level in rats with a model of diabetes mellitus after 15 days of administration of the clathrate complex of 20-hydroxyecdysone with arabinogalactan and the reference drug metformin

No. Groups Number of animals Glucose content, mmol/l initially for 3 days for 7 days for 15 days one Control eight 5.45±0.11 12.48±2.45 13.69±2.88 14.36±3.73 2 Metformin eight 5.60±0.20 12.56±2.65 12.36±2.99 10.14±2.37 3 Suggested Complex, 1.0 mg/kg eight 5.73±0.19 11.90±2.25 10.69±2.19 7.90±0.78 ^*# four Proposed Complex, 10.0 mg/kg eight 5.85±0.13 12.75±3.04 10.73±2.71 7.62±0.88 ^*#

Note: hereinafter in the table: ^* P<0.05 according to U-test when compared with control;

^** P<0.10 by U-test when compared with control;

^*** P<0.05 by U-test when compared with metformin;

^# P<0.10 by U-test when compared with metformin.

The obtained data on the study of the activity of enzymes in the blood serum of rats with a model of diabetes mellitus showed that the proposed complex at doses of 1.0 and 10.0 mg/kg contributes to the stabilization and normalization of the main enzyme systems of the body (Table 3). In particular, the stabilizing effect of the proposed complex is most significant in the lactate dehydrogenase and phosphatase systems of the rat body against the background of the administration of streptozotocin (Table 3).

Control Metformin Doses of the proposed complex, mg / kg 1.0 10.0 Creatine phosphokinase (CPK), U/l 3818.6 ± 1237.7 7380.3 ± 1259.7 6853±1458.5 ^* 6442 ± 529.6 ^** Alanine aminotransferase (ALT), U/l 98.8 ± 14.2 102.0 ± 12.8 75.4±8.2 ^**# 84.8 ± 6.5 Aspartate aminotransferase (AST), U/l 199.8 ± 18.3 235.5 ± 11.9 228.2 ± 18.8 201.8 ± 9.0 Lactate dehydrogenase, (LDH) U/l 2386.2 ± 80.8 2379.7 ± 101.8 2189.9 ± 181.8 1808 ± 142.2 ^*# Alkaline phosphatase (AP), U/l 397.6 ± 26.3 571.2 ± 121.1 548.5 ± 53.9 ^*# 546.8 ± 32.2 ^*#

Table 3 - Activity of enzymes in the blood serum of rats with a model of diabetes mellitus with a 15-day administration of the clathrate complex of 20-hydroxyecdysone with arabinogalactan and the reference drug metformin

When assessing the level of urea in the blood serum of rats, a significant increase in its content was revealed in streptozotocin-induced diabetes mellitus (up to 9.1 mol/l in some animals) compared with the norm indicated in the literature (5.18 mol/l ± 0, 38 mol/l) [Kaveshnikova S. V., Ivanov V. M. Biochemical characteristics of the blood of Wistar rats in postnatal ontogenesis during their intoxication with nitrogen oxides// Bulletin of the Stavropol State University 2011,-74. - from 100-105]. With the introduction of the proposed complex in doses of 1.0 and 10.0 mg/kg in rats, the urea content in the blood serum decreases to the normal level (Table 3). As for the level of creatinine in the blood serum, its concentration was statistically insignificant when the proposed complex was administered compared with the control and metformin (Table 4).

Table 4 - The level of urea and creatinine in the blood serum of rats with a model of diabetes mellitus after 15 days of administration of the clathrate complex of 20-hydroxyecdysone with arabinogalactan and the reference drug metformin

Control Metformin Doses of the proposed complex, mg / kg 1.0 10.0 Creatinine, µmol/l 39.90 ± 1.24 40.45±0.97 37.10 ± 2.04 37.20±0.75 Urea, mmol/l 8.05±0.56 6.00±0.54 6.08±0.50 ^* 5.88±0.31 ^*

The results of a comparative assessment of the effect of the proposed complex on the blood lipid profile of rats during the induction of diabetes mellitus in the streptozotocin model indicate significant changes compared to control and metformin (Table 5).

With the development of diabetes mellitus in rats, there was a statistically significant increase in the value of triglycerides to 2.67 mmol / l in individual rats (median (upper-lower quartile) - 1.78 (1.13-2.67)). The introduction of the proposed complex in doses of 1.0 and 10.0 mg/kg normalized the level of triglycerides in the blood serum - the values differed statistically significantly from the control group (Table 5).

The level of total cholesterol in the blood serum of rats increased during the development of experimental diabetes mellitus. Under the action of the proposed complex in doses of 1.0 and 10.0 mg/kg, the parameters normalized, while a statistically significant effect was noted compared to the control (Table 5).

As a result of measuring the level of cholesterol associated with HDL, LDL and VLDL, a decrease in the VLDL-C fraction was revealed against the background of minor changes in HDL-C values and a decrease in the calculated value of the atherogenic coefficient in the serum of rats receiving the proposed complex at doses of 1.0 and 10.0 mg / kg compared with control (Table 5).

Table 5 - Indicators of lipid metabolism in the blood serum of rats with a model of diabetes mellitus after 15 days of administration of the clathrate complex of 20-hydroxyecdysone with arabinogalactan and the reference drug metformin

Control Metformin Doses of the proposed complex, mg / kg 1.0 10.0 Triglycerides, mmol/l 1.78±0.25 1.28 ± 0.13 0.92 ± 0.13 ^*# 1.37 ± 0.13 ^** Total cholesterol, mmol/l 1.80±0.06 1.51±0.15 1.50±0.08 ^* 1.60±0.03 ^* Cholesterol-HDL mmol/l 1.00±0.02 0.84 ± 0.08 0.89±0.04 0.95±0.04 Cholesterol-VLDL mmol/l 0.71 ± 0.11 0.57 ± 0.06 0.50 ± 0.07 ^* 0.53±0.04 ^* Cholesterol-LDL mmol/l 0.09±0.1 0.10±0.03 0.11 ± 0.02 0.12 ± 0.04 Atherogenic coefficient 0.80±0.04 0.79 ± 0.04 0.68± 0.06 ^*# 0.68 ± 0.06 ^*#

Thus, based on the results of the lipid profile assessment, it can be concluded that the administration of streptozotocin to rats on the background of a standard diet, along with carbohydrate metabolism disorders, leads to an increase in the levels of triglycerides, total cholesterol, VLDL cholesterol and a decrease in the content of HDL cholesterol in the blood serum. This picture can be characterized as the basis for the further development of metabolic disorders. The introduction of the proposed complex at doses of 1.0 and 10.0 mg/kg is associated with a statistically significant effect, characterized by a decrease in the levels of triglycerides, total cholesterol and VLDL cholesterol in the blood serum, against the background of a decrease in the calculated value of the atherogenic coefficient. The use of the proposed complex leads to the normalization of lipid metabolism.

As a result of the studies, it was experimentally found that against the background of diabetes mellitus induced by streptozotocin, the clathrate complex of 20-hydroxyecdysone with arabinogalactan normalizes metabolism in rats.

EXAMPLE 2. The clathrate complex of 20-hydroxyecdysone with arabinogalactan, which provides an increase in resistance, antioxidant status of the body, growth and development, was studied in experiments on rabbits of the Soviet Chinchilla breed.

The experiment was carried out on 18 rabbits of the Soviet Chinchilla breed in the period from 6 to 18 weeks of age. 3 groups of 6 rabbits were formed. Animals of the 1st group (control) were injected with a suspension of arabinogalactan in starch gel; group 2 - clathrate complex of 20-hydroxyecdysone with arabinogalactan at a dose of 1.0 mg/kg; group 3 - clathrate complex of 20-hydroxyecdysone with arabinogalactan at a dose of 5.0 mg/kg. Animals were kept in individual cages under artificial lighting conditions (12 hours of light and dark time) with forced ventilation 16 times per hour, at a temperature of 18-20 °C and a relative humidity of 50-65%

The rabbits were weighed before the morning meal every 2 weeks for 85 days. During the experiment, feed consumption was recorded and their chemical composition was studied. During the experiment, blood was taken 2 times: 45 and 75 days after it began. Blood was taken from the marginal vein of the rabbit's ear in a volume of 2.0-2.5 ml. To determine the indicators of nonspecific resistance of the rabbit organism, blood was taken into polypropylene tubes without anticoagulants in order to obtain serum. Blood serum was separated by centrifugation at 4000 rpm. within 15 min. Serum samples were frozen and stored at -20°C until analysis.

The nonspecific resistance of the organism of experimental rabbits was assessed on the basis of determining the bactericidal activity of blood serum (BASK) and the lysozyme activity of blood serum (LASK). BASK was determined according to the method of Munsel and Treffens modified by O.V. Smirnova and T.N. Kuzmina and LASK according to Dorofeichuk [Karput, I.M. Recommendations for the diagnosis and prevention of immunodeficiencies and autoimmune diseases in animals / I.M. Karput [i dr.]. Vitebsk, 1992, p. 79]. The antioxidant status of the organism of rabbits was assessed based on the determination of the concentration of malondialdehyde (MDA) and the activity of the enzymatic unit of the antioxidant system in the blood. The concentration of MDA in blood plasma was determined using KMnO ₄ and FeSO ₄ according to the method described in the article below [Osipov AN, Ryabchenko NI., Ivannik BP, Dzikovskaya LA., Ryabchenko VI., Kolomijtseva G.Ya. A prior administration of heavy metals reduces thymus lymphocyte DNA lesions and lipid peroxidation in gamma-irradiated mice.// J.Phys.IV France – 2003 – Vol. 107 - P.987-992]. Analysis of the state of the enzymatic link of the antioxidant system was assessed based on the determination of the activity of superoxide dismutase (SOD) and catalase in the erythrocyte lysate. Determination of SOD activity in erythrocytes was carried out by the enzymatic method on an RX Monza biochemical analyzer (Great Britain) using Randox SD 125 commercial kits (Great Britain). The method is based on enzyme inhibition of the reaction of interaction between superoxide anion radicals and 2-(4-iodophenyl)-3-(4-nitrophenol)-5-phenyltetrazolium chloride to form a red-colored compound, formazan. Catalase activity in erythrocyte lysate was determined spectrophotometrically by the generally accepted method [Korolyuk M.A., Ivanova L.I., Mayorova I.G., Tokarev V.E. Method for determining catalase activity. Laboratory work. 1988; 1: 16–19.] at a wavelength of 420 nm, the principle of which is based on the ability of hydrogen peroxide to form a stable colored complex with ammonium molybdate. Erythrocyte catalase activity was expressed as the amount of utilized hydrogen peroxide in µmol per 1 min per one erythrocyte, pkat/erythrocyte. For this purpose, the erythrocyte hemolysate was diluted in such a way that 10×10 ⁶ cells got into the reaction mixture.

Animal growth has two aspects. The first is associated with an increase in body weight per unit of time. The second includes a change in the shape and composition of the body, due to the differential growth of its constituent parts. Understanding how animals grow can lead to the development of methods for controlling growth processes, finding ways to increase efficiency or produce higher quality products.

As a result of the studies, it was found that the introduction of a clathrate complex of 20-hydroxyecdysone with arabinogalactan at doses of 1.0 and 5.0 mg/kg of body weight compared with the control for 69 days allowed a statistically significant increase in absolute and average daily gains by 32-38%. body weight of rabbits (Table 6). The best results were obtained when the proposed complex was administered to rabbits at a dose of 1.0 mg/kg of body weight. At the end of the experiment, the body weight of rabbits treated with the proposed complex at doses of 1.0 and 5.0 mg/kg, respectively, was 3062 and 3086 g or was higher by 15.4 and 16.3% than in animals of the control group. At the same time, the introduction of the proposed complex at doses of 1.0 and 5.0 mg/kg ensured an increase in the efficiency of feed use by rabbits, namely, it statistically significantly reduced the cost of feed per 1 kg of body weight gain compared to animals in the control group. Similar changes were observed in the cost of crude protein and metabolic energy per unit of production (Table 7).

The immune status of an organism can be determined using various indicators characterizing the level of protective properties of an animal. BASK and LASK were considered as criteria for assessing the formation of nonspecific resistance in experimental rabbits with the introduction of the proposed complex.

The results of studies of nonspecific resistance showed that the introduction of a clathrate complex of 20-hydroxyecdysone with arabinogalactan to rabbits at doses of 1.0 and 5.0 mg/kg of body weight compared to the control for 69 days significantly increases the levels of BASK and LASK (Table 8) . It should be noted that comparable results were obtained when the clathrate complex was administered to rabbits both at a dose of 1.0 mg/kg and 5.0 mg/kg of body weight.

The obtained data on the antioxidant status of the body of rabbits indicate that the introduction of the clathrate complex of 20-hydroxyecdysone with arabinogalactan at doses of 1.0 and 5.0 mg/kg of body weight compared with the control for 69 days statistically significantly increases the activity of the non-enzymatic and enzymatic link antioxidant system. In particular, the activities of catalase and SOD enzymes in the erythrocyte lysate in rabbits treated with the clathrate complex in two studied doses were statistically significantly higher compared to the control (Table 9).

Thus, the introduction of the clathrate complex of 20-hydroxyecdysone with arabinogalactan to rabbits ensures the normalization of metabolism, an increase in nonspecific resistance and antioxidant status of the body, growth and development of animals.

Table 6 - Growth and development of rabbits with a 69-day administration of a clathrate complex of 20-hydroxyecdysone with arabinogalactan at doses of 1.0 and 5.0 mg/kg of body weight (M±m, n=6)

Indicators Groups control 1st experienced 2nd experienced Preliminary period (before administration - within 14 days) Body weight at the beginning, g 1128±103.9 1191±89.5 1191 ± 85.2 Body weight at the end, g 1454 ± 111.0 1404±50.5 1502±60.0 Absolute weight gain, g 285±60.4 260±24.3 312 ± 35.0 Average daily weight gain, g 20.4 ± 4.31 18.6 ± 1.73 22.3± 2.50 The main period (69 days after the administration of the drug) Body weight at the beginning, g 1454 ± 111.0 1404±50.5 1502±60.0 Body weight at the end, g 2653 ± 143.3 3062±21.6 ^* 3086±62.4 ^* Absolute weight gain, g 1199± 117.0 1658 ±71.4** 1583 ± 74.2* Average daily weight gain, g 17.4 ± 1.69 24.0 ± 1.03** 23.0± 1.07* Relative growth, % 58.80±5.21 74±3.70 ^# 69.13± 3.51 CW (specific growth rate, 1/day 0.02±0.005 0.025± 0.003 ^* 0.023±0.003 K (growth constant) 1.40±0.33 1.81±0.23 ^# 1.61 ± 0.18

Note: hereinafter in the table: ^* P<0.05 according to U-test when compared with control

^** P<0.01 according to U-test when compared with control

^# Р<0.02 by U-test when compared with control

^& P<0.02 by U-test when compared with control

^@ P<0.004 U-test vs control

^$ Р<0.03 by U-test when compared with control

^% Р<0.04 according to U-test when compared with control

Table 7 - Efficiency of feed use by rabbits with a 69-day administration of a clathrate complex of 20-hydroxyecdysone with arabinogalactan at doses of 1.0 and 5.0 mg/kg of body weight (M±m, n=6)

Indicators Groups control 1st experienced 2nd experienced The main period (69 days after the administration of the drug) Feed consumed per head, kg 10.45 ± 1.05 8.46 ± 1.52 9.37±0.83 Feed consumption per unit of growth, kg 7.26±0.97 4.89±0.72 ^# 5.85±0.88 ^& Exchange energy consumption per unit of growth, MJ 66.54 ± 9.93 43.32±6.92 ^# 51.82±8.84 ^& Protein consumption per unit of growth, kg 1.11±0.15 0.72±0.11 ^# 0.88±0.12 ^&

Table 8 - Indicators of nonspecific resistance of the organism of rabbits with a 69-day administration of the clathrate complex of 20-hydroxyecdysone with arabinogalactan at doses of 1.0 and 5.0 mg/kg of body weight (M±m, n=6)

Indicators Groups control 1st experienced 2nd experienced BASK, % 52.38±3.01 61.90±3.01 ^* 64.28±3.19 ^& LASK, % 47.12±0.47 53.22±1.52 ^# 54.90±0.99 ^#

Table 9 - Indicators of the antioxidant status of the body of rabbits with a 69-day administration of the clathrate complex of 20-hydroxyecdysone with arabinogalactan at doses of 1.0 and 5.0 mg/kg of body weight (M±m, n=6)

Indicators Groups control 1st experienced 2nd experienced After 45 days Catalase, pkat/erythrocyte 52.38±3.01 61.90±3.01 ^* 64.28±3.19 ^& SOD, U/g Hb 40.4±5.51 59.4±5.76 ^{* $} 63.75±4.25 After 75 days SOD, U/g Hb 49.4±1.78 76.0±7.35 ^** 71.±8.59 ^$ Catalase, pkat/erythrocyte 48.4±1.75 56.0±1.76 ^# 56.20±2.80 ^* MDA, µmol/l 13.96±1.39 9.17±0.47 ^{@ $} 10.24±0.60

Claims (1)

The use of a clathrate complex containing 20-hydroxyecdysone and arabinogalactan to increase nonspecific resistance, antioxidant status of the body, growth and development of animals.