RU2623071C1 - Treatment-and-prophylactic chelate iron containing drug for farm animals - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: treatment-and-prophylactic chelate iron-containing drug for farm animals, includes iron gluconate, with III valency, vitamins B₁₂, B₃ and water at the following component ratio, wt %: iron gluconate (III) 20.0-80.0, vitamin B₁₂ 1.5-5.0, vitamin B₃ 1.5-10.0, water for injection - the rest.

EFFECT: use of the claimed invention allows to compensate and prevent the iron deficiency of farm animals, to increase immunity, improve the growth and development of animals.

4 tbl, 4 ex

Description

FIELD OF THE INVENTION

The invention relates to veterinary medicine, namely to pharmacology and therapy. The drug can be used for the prevention and treatment of iron deficiency anemia of farm animals.

State of the art

Known iron-containing drug, which provides for a double intramuscular injection of iron preparations at a dose of 2-8 ml / goal for the first 10 days of animal life (100-375 mg Fe). The proposed method replaces the repeated injection of iron with a solution containing zinc glycinate, copper glycinate and potassium iodide (see US Pat. RU No. 2135173, IPC A61K 31/295, A61K 31/30, A61K 31/315, A61K 33/18 publ. 27.08. 1999).

The disadvantage of this drug is the lack of vitamins.

Known drug for the prevention and treatment of anemia. The drug provides, in comparison with analogues, a decrease in the content of dextran in the dosage form and the stability of aqueous solutions of the agent in a concentration of from 1 to 99% for 24 months. The drug contains irondextran and sorbitol in the following ratio of components, wt. %:

iron dextran 78-90 sorbitol 10-22

(see Pat. RU No. 2338516, IPC A61K 31/047, A61K 31/721, A61P 7/06, published on November 20, 2008).

The disadvantage of this drug is high toxicity, lack of digestibility of iron.

A known method for the prevention and treatment of nutritional anemia and the prevention of hypoplastic anemia in piglets. The method includes the introduction of feed preparations containing iron. At the same time, piglets from 30 days of age are additionally injected with a probiotic preparation - hydrolyzed milk whey in a volume of 2 ml per kilogram of body weight once a day with a preventive purpose for 1 month. For therapeutic purposes, hydrolyzed milk serum is administered to piglets for 2 months in the same doses. The method contributes to the normalization of microbiocenosis, activation of the enzymatic activity of the gastrointestinal tract by increasing the bifidogenic factor, increasing the digestibility of feed and bioavailability of protein-mineral-vitamin complexes introduced into these feeds (see US Pat. RU No. 2429863 IPC A61K 35/20, A61K ЗЗ / 26, published September 27, 2011).

The disadvantage of this drug is the lack of vitamins, insufficient digestibility of iron.

The closest in technical essence and the achieved positive effect and adopted by the authors for the prototype is iron (II) gluconate. This iron preparation compensates for the deficiency of iron in the body, restores hemoglobin. With a course of treatment, it contributes to the regression of clinical and laboratory symptoms of anemia, is a highly absorbable and well-tolerated form of iron. Iron gluconate is more easily absorbed than iron salts of inorganic origin. The drug is intended for oral use, which creates certain inconveniences for staff in the conditions of the livestock complex. (Troshin A.N., Nechaeva A.V. Iron-proteinate ferroquin for the stimulation of hematopoiesis in pregnant sows // Modern high technology. 2007. No. 3. P. 35-36).

The disadvantage of this drug is the lack of vitamins, high toxicity and inconvenience of the drug, because iron in the composition of the preparations is in the ionic form of Fe (II), which causes a disturbance in the function of the gastrointestinal tract (diarrhea, vomiting, decreased appetite, dysbiosis, etc.).

Disclosure of invention

The objective of the invention is the creation of a therapeutic and prophylactic chelated iron-containing preparation for farm animals, replenishing iron deficiency in young farm animals, improving the growth and development of animals, as well as combining high biological activity, low toxicity and good tolerance compared to drugs used in veterinary medicine.

The technical result that can be achieved using the present invention is to compensate for iron deficiency in animals, increase immunity, improve growth and development of animals.

The technical result is achieved using a therapeutic prophylactic chelated iron-containing preparation for farm animals, including iron gluconate, characterized in that iron gluconate is taken in valency III and additionally contains vitamins B ₁₂ , B ₃ and water in the following ratio of components, wt. %:

iron (III) gluconate 20.0-80.0 vitamin B ₁₂ 1,5-5,0 vitamin B ₃ 1,5-10,0 water for injections rest

The essence of obtaining a therapeutic and prophylactic chelated iron-containing preparation for farm animals is as follows: starting materials in wt. %, namely: iron gluconate 20.0-80.0; vitamin B ₁₂ 1.5-5.0; Vitamin B ₃ 1.5-10.0 and water for injection, mixed under aseptic conditions and packaged.

The pharmacological effect of the drug lies in the fact that iron deficiency is compensated by intake from the outside, while conditions are created for the accumulation of iron and an increase in its level in blood plasma, bone marrow, and red blood cells.

Iron in animals is in the form of organic and inorganic compounds and makes up about 0.005% of the total mass. In the animal’s body, this element is more than 90% bound to proteins: hemoglobin, myoglobin, transferrin, ferritin. In animal products, iron is in the form of gems in the structure of hemoglobin or in the form of inorganic and protein compounds. For the effective use of iron from its compounds by animals, it is necessary that it be converted from a trivalent form to a divalent form. This is carried out during ionization with hydrochloric acid contained in the gastric juice, as well as in the presence of compounds such as ascorbic acid and cysteine in the tissues of the body. Bivalent iron is absorbed by the cells of the intestinal mucosa, primarily by the cells of the duodenum, where it combines with apoferritin and again goes into the trivalent form. The compound formed in this way in the liver cells is called ferritin (A. Aliev, Prevention of metabolic disorders in farm animals / A. Aliev, V. Barey, P. Bartko, J. Buda and others. - M .: Agropromizdat, 1986. - 385 p.).

An important role in providing the body with iron belongs to the reserve iron, the reserves of which can be depleted in cases of impaired normal absorption from the intestine, especially in diseases. Insufficient intake of iron from the outside creates the conditions for the development of iron deficiency anemia, characterized by the absence of accumulated iron and a decrease in its level in blood plasma, bone marrow, and red blood cells.

On average, it is estimated that 20–25% of animals die due to iron deficiency, this issue is especially acute in the pig and fur farming industries. Despite the large number of works devoted to this problem, it remains unsolved by science and veterinary practice.

Vitamin B ₁₂ is a cobalt-containing complex compound. It regulates the process of hematopoiesis, the process of transmethylation of choline, methionine, creatine, nucleic acids and nucleotides, and also promotes the accumulation of compounds containing sulfhydryl groups in red blood cells. Methionine helps increase the biological value of plant diets (contributes to better absorption of amino acids of plant proteins).

Vitamin B ₁₂ is a growth factor, has a beneficial effect on the liver and nervous system. Vitamin B ₁₂ is involved in hematopoiesis, the synthesis of methyl groups, and the isomerization of methylmalonic acid. These reactions are of great importance in the metabolism of amino acids, as well as volatile fatty acids. It is especially necessary for normal reproduction in sows, their provision prevents abortion, allows you to get healthy, well-developed piglets.

Vitamin B ₃ - a vitamin that is involved in many redox reactions, the formation of enzymes and the metabolism of lipids and carbohydrates in living cells, a drug.

Vitamin, lipid-lowering and specific anti-pellagric agent. In the body, nicotinic acid is converted into nicotinamide, which binds to coenzymes of codehydrogenase I and II (NAD and NADP), which carry hydrogen, is involved in tissue respiration, metabolism of fats, proteins, amino acids, purines, glycogenolysis, and biosynthesis processes. Expands small blood vessels (including the brain), improves microcirculation, has a weak anticoagulant effect, increasing blood fibrinolytic activity. It has detoxification properties.

Brief description of drawings and other materials

In the table. 1 given a therapeutic and prophylactic chelated iron-containing preparation for farm animals, morphological and biochemical blood parameters prior to the introduction of a therapeutic and preventive chelated iron-containing preparation to rabbits (n = 12).

In the table. 2 - the same, the effect of different concentrations of therapeutic and prophylactic chelated iron-containing preparation on the morphological and biochemical parameters of rabbits (n = 12).

In the table. 3 - the same, hematological and biochemical blood parameters before treatment of guinea pigs with therapeutic and prophylactic chelated iron-containing preparation (n = 30).

In the table. 4 - the same, comparative therapeutic efficacy of therapeutic and prophylactic chelated iron-containing preparation in guinea pigs (n = 30).

The implementation of the invention

Examples of specific performance of obtaining therapeutic chelate iron-containing drug

Example 1. Obtaining a therapeutic and prophylactic chelated iron-containing preparation for farm animals, is as follows: the starting materials are iron (III) gluconate, vitamins B ₁₂ , B ₃ and water, mixed under aseptic conditions and packaged in the following ratio of components, wt. %:

iron (III) gluconate 20,0 vitamin B ₁₂ 1,5 vitamin B ₃ 1,5 water for injections rest

Animals for experiments were selected in groups according to the principle of analogues taking into account gender, age, breed, body weight and were in the same conditions of feeding and keeping. 4 groups were formed, in each group there were 3 females. The therapeutic and prophylactic chelated iron-containing preparation for farm animals was administered at a dose of 1 ml per 1 kg of animal body weight, intramuscularly. On the 7th day after the administration, the blood was examined for some morphological and biochemical parameters: red blood cells, hemoglobin, white blood cells, and serum iron.

This composition of the dosage form showed a slight increase in the percentage of iron in animals of group 1, which is necessary to exclude iron deficiency, and, accordingly, hemoglobin and red blood cells (Table 2).

Example 2. Carried out analogously to example 1, but take the following ratio of components, wt. %:

iron (III) gluconate 40,0 vitamin B ₃ 2.5 vitamin B ₁₂ 3.0 water for injections rest

This composition of the dosage form showed positive dynamics in animals of the 2nd group. The hemoglobin level increased by 18.8%, and the amount of serum iron in the blood increased by 10.8% (Table 2).

Example 3. Carried out analogously to example 1, but take the following ratio of components, wt. %:

iron (III) gluconate 80.0 vitamin B ₁₂ 5,0 vitamin B ₃ 10.0 water for injections rest

This composition of the dosage form also showed positive dynamics in animals of group 3. 7 days after the administration of the drug, the hemoglobin level increased by 30.1%, and the amount of serum iron in the blood of rabbits increased by 19.6% (Table 2).

Example 4. Carried out analogously to example 1, but take the following ratio of components, wt. %:

iron (III) gluconate 85.0 vitamin B ₁₂ 7.0 vitamin B ₃ 12.0 water for injections rest

7 days after the use of this drug, in animals of the 4th group, the leukocyte count increased, which indicates a high load on the protective function of organisms (Table 2).

Thus, the most optimal composition of the dosage form of the drug is the preparation according to example 3 (group 3), which was tested on laboratory white mice, guinea pigs and rabbits.

To determine lethal doses of the drug, clinically healthy white mice weighing 20-22 g are used, studies are carried out according to the “Methodological guidelines for the toxicological evaluation of new drugs for the treatment and prevention of non-communicable animal diseases” (All-Russian Research Institute of Non-communicable Animal Diseases, 1987).

Acute Toxicity Study

Studies show that a therapeutic and prophylactic chelated iron-containing preparation for farm animals with enteral (intragastric) administration in doses from 2011.1 to 6150.0 mg / kg (a.a.) body weight for white mice does not cause visible clinical signs of toxicosis . After the administration of 6150.0 mg / kg in the first two hours of the experiment, the mice were mobile, there was no anxiety and excitement.

Tested doses are 30 times superior to therapeutic. A further increase in the administered dose is not possible, since the maximum volume of intragastric administration of preparations for white mice cannot exceed 0.6 ml; therefore, it was not possible to establish the exact values of MTD, LD ₅₀ , and LD ₁₀₀ . The ratio of the maximum dose administered to the intended therapeutic therapeutic index is 20.

As a result of the studies, it was found that the drug data on the degree of exposure to the body in accordance with GOST 12.1.007-76 standards belong to the 4th hazard class - low-hazard substances.

Study of local action on the mucous membranes

The results of staging a conjunctival test in rabbits show that after the installation of the drug, the clinical condition of the animals remains within the physiological norm. No changes in the blood supply to the vessels of the conjunctiva, the presence of lacrimation and secretions, changes in the state of the cornea and eyelids.

The study of allergenic properties

Studies have shown that with sensitization of the animal organism through daily applications of drugs for ten days, there are no changes in the general condition of animals, as well as local changes in the skin (edema, hyperemia, etc.).

The study of the therapeutic effectiveness of therapeutic and chelating iron-containing preparation for farm animals.

In order to study the effect of therapeutic and prophylactic chelated iron-containing preparation for farm animals on the main morphological and biochemical parameters of blood, anemia was modeled on guinea pigs (females). Animals for the experiments were selected in groups taking into account age, body weight and were in the same conditions of feeding and keeping. All hematological and biochemical studies were carried out on a PCE-90Vet automatic veterinary hematological analyzer and a ChemWell automatic veterinary biochemical analyzer.

Digital material is processed by methods of variation statistics. The significance of differences is determined by the Fisher F-test. The difference is considered significant at p <0.05.

Modeling of anemia was carried out according to the Workshop on the pathological physiology of farm animals. - M .: Agropromizdat, 1989 .-- 272 p.: Ill. - (Textbooks and study guides for students of higher educational institutions).

On day 4 from the beginning of the modeling of anemia, a clear pallor of mucous membranes was observed in the tested animals in groups 1 and 2, and blood was taken from the heart on day 4 to confirm the development of anemia in animals (Table 3).

On day 5, the first group was intramuscularly injected with a therapeutic chelate iron-containing preparation for farm animals at a dose of 1 ml per 1 kg of body weight, and the second group - a drug analogue Ursoferran - 200, at a dose of 1 ml per 1 kg of body weight.

On the 15th day, blood cares were performed from the heart of guinea pigs to compare the effectiveness of the therapeutic and prophylactic chelated iron-containing preparation for farm animals and the analogue preparation (Table 4).

As a result of the analysis of the results, no significant differences were found in the number of leukocytes, lymphocytes, monocytes in guinea pigs of the experimental groups. In the control group of guinea pigs, a significant decrease in lymphocytes by 9.8% was found.

Analyzing the results obtained, it is possible to note the positive effect of the introduction of a therapeutic chelate iron-containing preparation for farm animals on some hematological parameters: the number of red blood cells and the level of hemoglobin. It was found that the introduction of the drug increases the level of hemoglobin in the blood of guinea pigs by 8.0% in the second group and by 13.1% in the first, and helps to increase the number of red blood cells by 5.5% and 12.5%, respectively. This helps to increase the average content and average concentration of hemoglobin in red blood cells (table. 4).

The average anisocytosis is an indicator of blood degeneration, often observed with anemia and severe septic diseases; in some pathological conditions in the bloodstream appear red blood cells with a changed shape - pear-shaped, round, sickle-shaped, etc. [5]. In all experimental groups, the average anisocytosis is within the physiological norm.

When analyzing the biochemical parameters of blood serum, a significant increase in iron content was found in guinea pigs of the first experimental group by 1.8%, in guinea pigs of the second experimental group - by 0.9% (Table 4).

The introduction of the drug increases the total protein content in guinea pigs of the first and second groups, respectively, by 8.7% and 4.3%. In the body, the total protein performs the following functions: participates in blood coagulation, maintains a constant blood pH, performs a transport function (transfer of fats, bilirubin, steroid hormones to tissues and organs), and participates in immune reactions.

Thus, the conducted testing allows us to conclude that the use of therapeutic and prophylactic chelated iron-containing preparation for farm animals is an effective way to prevent nutritional anemia for animals.

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

- the new drug developed according to the degree of exposure to the body belongs to the 4th hazard class - low-hazard substances;

- affects the growth and development of animals;

- Replenishment of iron deficiency in animals;

- comfortable in using;

- high preventive and therapeutic effect.

Claims (2)

Therapeutic prophylactic chelate iron-containing preparation for farm animals, including iron gluconate, characterized in that iron gluconate is taken in valency III and additionally contains vitamins B ₁₂ , B ₃ and water in the following ratio of components, wt. %: iron (III) gluconate 20.0-80.0 vitamin b ₁₂ 1,5-5,0 vitamin b ₃ 1,5-10,0 water for injections rest