RU2620554C2 - Content for stimulating metabolic processes, immune system, prevention the diseases and diarrhea - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: declared composition has metabolic, immunomodulating and antimicrobial activity for preventing gastrointestinal diseases with diarrhea syndrome, comprising succinic acid and SDA iodinol second fraction with the following ratio of components per 1000 ml of aqueous solution: Succinic Acid - 10.0 g iodinol - 250 ml of SDA second fraction - 40 ml. The following is also claimed: composition having metabolic, immunomodulating and antimicrobial activity for preventing gastrointestinal diseases diarrhea syndrome comprising succinic acid, iodinol, levamisole with the following ratio of components per 1000 ml of aqueous solution: Succinic Acid - 10.0 g iodinol - 250 ml , levamisole - 10.0 g.

EFFECT: stimulation of metabolism and the immune system, prevention of gastrointestinal diseases, and increase the activity of the growth of young farm animals.

2 cl, 6 tbl, 3 ex

Description

The invention relates to veterinary medicine and can be used in animal husbandry to stimulate metabolic processes and the immune system, the prevention of gastrointestinal diseases and increase the growth activity of young farm animals.

The issues of ensuring the health of young farm animals in industrial animal husbandry are very problematic tasks in veterinary science and practice. The current intensification of animal husbandry has led to a number of negative factors that have an extremely negative effect on the state of animal health. At present, metabolic disorders and immunodeficiencies, to one degree or another, occur in animals from the first days of life. The body of such animals is very sensitive to infectious pathogens. Hence the high rates of gastrointestinal diseases in young animals.

Gastrointestinal diseases of farm animals are etiologically associated with viruses, microbes, protozoa, fungi, and develop against a background of various adverse factors of keeping and feeding.

For the prevention and treatment of gastrointestinal diseases of young farm animals, chemo-antibiotic therapy, adsorbents, various stimulants of metabolic and immune processes, pro- and prebiotics are widely practiced. In the vast majority of cases, these funds are used as monopreparations. The narrow focus of these funds often does not give a positive result and has a negative side effect.

So, the use of antibiotics for gastrointestinal diseases has led to the selection of drug-resistant strains of microorganisms.

In addition, many antibiotics have hepato- and nephrotoxicity, which reduces the detoxification activity of the liver and the excretory ability of the kidneys.

The preventive use of pro- and prebiotics is often associated with the development of dysbiosis and does not provide the necessary therapeutic and prophylactic effect.

The use of stimulants of metabolic and immune processes can increase the body's defenses, but this is not enough to prevent gastrointestinal diseases.

The objective of the present invention is to develop a complex composition with a metabolic, immunomodulating and antimicrobial effect, hepatoprotective activity, the use of which would cause a systemic therapeutic effect in gastrointestinal diseases with diarrheal syndrome.

Known complex antimicrobial drug iodinol. Iodinol includes in its composition: crystalline iodine - 1 part; potassium iodide - 3 parts; polyvinyl alcohol - 10 parts; distilled water - 1000 parts (Mozgov I.E. Pharmacology, 1979. - S. 290-291). The resistance of microorganisms to iodine preparations does not develop. The advantage of the use of iodine preparations in infectious diseases is the lack of addiction of microorganisms to them. However, along with high antimicrobial activity, their use per os is contraindicated in case of renal failure and low functional activity of the liver. In addition, with prolonged use, phenomena of iodism (an excess of iodine in the body) can be observed.

The use of succinic acid and its salts (succinates) is known to improve the pharmacological activity and reduce the toxic effects of drugs (Kovalenko A.L., Belyakova N.V. Succinic acid: pharmacological activity and dosage forms. Pharmacy 2000, No. 5-6. - S. 40-42). The absolute harmlessness of succinic acid and its derivatives, the ability to have a positive effect even at absolutely low dosages, to enhance the effect of other drugs make it very valuable in the development of complex preparations, feed and food additives.

It is known the use of ASD of the second fraction (Dorogov antiseptic stimulator - ASD F - No. 2) for the treatment of gastrointestinal diseases and stimulation of the immune system. When administered orally, the ASD drug has an activating effect on the central nervous system and autonomic nervous system, stimulates the motor activity of the gastrointestinal tract, secretion of digestive glands, increases the activity of digestive and tissue enzymes, improves the penetration of Na + and K + ions through cell membranes, and helps normalize digestion and assimilation nutrients and increase the body's natural resistance. (Veterinary legislation of the USSR, Vol. No. 2. Manual on the use of ASD of the second fraction in veterinary practice of July 16, 1958. P. 87-89).

A complex immunometabolic preparation based on succinic acid and an ASD of the second fraction is known - “Amber biostimulant” (RF Patent No. 2303979, 2007). However, the neutralization of the alkaline reaction in the preparation of ASD F-2 with succinic acid led to the loss of antimicrobial activity.

Known complex immunotropic antiseptic drug for the treatment and prevention of infectious diseases of animals (RF Patent No. 2361579 from July 20, 2009). The preparation includes succinic acid 1%, ASD of the second fraction 4%, formalin 0.3%. The inclusion of formalin in the composition of the drug provides high anti-infective activity with the injection method of administration. Nevertheless, it was found that after three months of storage, the anti-infective activity of the drug decreases.

The use of succinic acid is known to potentiate the biological activity of levamisole, with a marked reduction in toxicity (RF Patent No. 2411944 of February 20, 2011. Immunometabolic anthelmintic drug). The drug includes an immunomodulator-anthelmintic levamisole, succinic acid and water in the following ratio, wt. %: levamisole 7.5, succinic acid 1.0; water the rest.

It is known that succinic acid is included in the composition of iodinol in an amount of 1%, which made it possible to improve its pharmacological properties, in particular, to reduce the risk of iodism phenomena with prolonged use. (RF patent No. 2486908 of July 10, 2013. A method for producing an antiseptic drug with metabolic and hepatoprotective activity). However, in this composition there is no component with immunostimulating activity.

The objective of the present invention was to obtain a complex composition with metabolic, immunomodulating and antimicrobial activity for the prevention of gastrointestinal diseases with diarrheal syndrome.

To solve this problem, a composition is proposed that includes succinic acid as a metabolism, as the immunomodulator of the second fraction ASD or levamisole, as an antimicrobial component, iodinol with the following components in 1000 ml of an aqueous solution: succinic acid - 10.0 g; iodinol - 250 ml; ASD of the second fraction - 40 ml or levamisole - 10.0 g.

The main energy component in the composition is succinic acid (UC). UC is a powerful stimulator of energy production in cells, which is especially important for various pathophysiological conditions, including digestion. As you know, digestion processes are associated with significant energy costs. In this regard, UC, providing energy to the cells of the mucous membrane of the stomach and intestines, improves digestion. Oral administration of UC provides stimulation of the immune system, which is very important for increasing the body's defenses. In medicine, UC preparations are used to enhance the secretion of gastric juice, hepatitis and toxicosis.

The stimulating effect of succinic acid is especially pronounced when weakening the body and its disease.

As an antimicrobial component, iodinol is included in the composition. Iodinol and its medical analogue “blue iodine” have pronounced antimicrobial activity, have long been used in gastrointestinal diseases of infectious etiology. The drug iodinol is well understood. For oral administration to piglets, it is recommended in an amount of 3-25 ml. The resistance of microorganisms to iodine preparations is not developed (IE Mozgov Pharmacology. Kolos, 1974. - P. 290-292).

The proposed composition allows to obtain simultaneously metabolic, immunomodulating and antidiarrheal effects.

The quantitative content of the components providing the above effects was found experimentally and is illustrated by the following experiment.

For the experiment, experimental series of compositions containing 100 ml of solution were prepared:

- 1 g of succinic acid, 4 ml of ASD of the second fraction, 25 ml of iodinol (according to the recipe 1);

- 1 g of succinic acid, 1 g of levamisole, 25 ml of iodinol (according to the recipe 2).

In parallel, similar solutions without iodinol were prepared. They were used as a control.

Growth activity was assessed in mice with initial body weight of 10–11 g. In each group, there were 5 mice. The above formulations were administered orally, forcibly, in a volume of 1 ml, three times with an interval of 24 hours. After 10 days, the experimental mice were weighed. The weighing results are presented in table 1.

When assessing the toxicity of the composition according to prescription 1, it was found that LD ₅₀ ranged from 25,000 to 26,500 mg / kg of body weight. The formulation 2 had an LD ₅₀ in the range of 27000-27500 mg / kg body weight.

Assessment of anti-infective activity

To assess the anti-infective activity, formulations 1 and 2 (including iodinol) were used. As a comparison, a similar concentration of iodinol and saline was used. In each group there were 7 mice. The average weight of mice is 19-21 g. For infection, a pre-titrated pathogenic culture of Salmonella (S. suis) was used, causing the death of at least 50% of individuals (LD ₅₀ ) with the oral method of infection. One hour after infection, the experimental formulations were orally administered twice to the experimental mice twice with an interval of 3 hours in a volume of 1.0 ml.

According to the results of the experiment it was found that the formulations 1 and 2 provided a higher level of protection for mice (table 2).

Methods of obtaining the claimed immunometabolic composition

Option 1. Upon receipt of the composition, first prepare a sample containing 10 g of succinic acid. A portion is introduced into a flask with 700.0 ml of pure tap water and heated until the succinic acid is completely dissolved. After cooling to 30 °, 250 ml of iodinol and 40 ml of second-stage ASD are poured into the flask. Water is added to 1000 ml of the solution. The composition is mixed.

Option 2. Prepare samples containing 10 g of succinic acid and 10 g of levamisole. A portion is introduced into a flask with 700.0 ml of pure tap water and heated until the succinic acid and levamisole are completely dissolved. After cooling to 30 °, 250 ml of iodinol are poured into the flask. Water is added to 1000 ml of the solution. The composition is mixed.

The resulting compositions were tested in the course of three scientific and production experiments. Place of experiments: pig farm "Hope" and the livestock complex of the farm "Znamenskoye" Kursk region.

Experience 1. Evaluation of the influence of the tested compounds on the hematological and biochemical processes of hypotrophic piglets

The objects for the experiments were hypotrophic piglets of 12 days of age. The first group of piglets (n = 5), for 14 days, with free access, instead of water, the formula 1 was evaporated; the second group (n = 5) composition according to the recipe 2. The third group (n = 5) was the control.

The influence of the tested compounds on the hematological and biochemical processes of hypotrophic piglets is presented in table 3.

The influence of the tested compounds on the stimulation of the growth activity of hypotrophic piglets is presented in table 4.

Experience 2. Evaluation of the use of compounds for the prevention of diarrhea in piglets of pre-withdrawal and early weaning periods

In testing, formulations 1 and 2 were used. Another group used iodinol when diluted in three parts of water.

Piglets were included in the experiment 3 days before they were weaned from their mothers. This period is associated with the activation of pathogens of gastrointestinal diseases.

Giving compositions was carried out for 7 days with free access to piglets. In the course of observations, it was found that on the second day the piglets of groups 1 and 2 began to eat food more readily than their peers from 3 and the control group.

The effect of the tested formulations on the incidence of diarrhea in piglets is presented in Table 5. According to the results of this experiment, it was found that the tested formulations 1 and 2 in comparison with iodinol provide a more pronounced acceleration of growth energy and lower rates of gastrointestinal diseases.

Experience 3. Evaluation of the use of compounds in the clinic for the treatment of diarrhea of newborn calves

The object for the experiments was newborn calves with the development of the first symptoms of diarrhea. The tested formulations of prescription 1, prescription 2 and iodinol were administered orally in a volume of 30 ml with 70 ml of boiled water added. The compositions were used 30 minutes before drinking milk before the symptoms of diarrhea stopped.

The effectiveness of the use of the compounds is shown in table 6.

According to the results of clinical observations, the tested formulations according to prescription 1 and according to prescription 2 provide a more pronounced reduction of the symptoms of diarrhea compared to iodinol.

Claims (8)

1. A composition having metabolic, immunomodulating and antimicrobial activity for the prevention of gastrointestinal diseases with diarrhea syndrome, including succinic acid, iodinol, characterized in that it additionally contains a second fraction ASD in the following ratio of components per 1000 ml of an aqueous solution: Succinic acid - 10.0 g Iodinol - 250 ml ASD of the second fraction - 40 ml. 2. A composition having metabolic, immunomodulating and antimicrobial activity for the prevention of gastrointestinal diseases with diarrhea syndrome, including succinic acid, iodinol, characterized in that it additionally contains levamisole in the following ratio of components per 1000 ml of an aqueous solution: Succinic acid - 10.0 g Iodinol - 250 ml Levamisole - 10.0 g.

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