RU2614996C1 - Medication for prevention and treatment of mycotoxicoses of small ruminants - Google Patents

Abstract

FIELD: agriculture.

SUBSTANCE: medication comprises humic acids, fine silica, selenium taken of small-size condition and zero valency, fat-soluble vitamin E, and distilled water. The components are taken in a specific ratio.

EFFECT: use of the invention enables to prevent and treat gastrointestinal diseases of animals, including those related to mycotoxins.

2 tbl, 4 ex

Description

FIELD OF THE INVENTION

The invention relates to veterinary toxicology and microbiology, in particular to a preparation for the prevention of mycotoxicosis of small cattle, and can be used for the prevention and treatment of gastrointestinal diseases of small cattle when using feeds infected with mycotoxins (T-2 toxin, deoxynivalenone, zearalenone, fumonisin, ochratoxin).

State of the art

Known EM drug "Baikal EM-1" in a mixture with infusion of phyto-collection in a ratio of 1: 1 according to the method of treatment of gastrointestinal diseases in calves, including a water-hungry diet, followed by the use of EM-drug "Baikal EM-1", while EM- the preparation “Baikal EM-1” is used in a mixture with the infusion of phyto-collection, which includes, per 100 ml of water, 0.5 g of perforated St. John’s wort grass, 0.5 g of common meadowsweet grass, 0.35 g of yarrow grass, 0.3 g of grass dioecious nettle, 0.2 rhizomes of frankincense, 0.2 g of roots and rhizomes of saber marsh th and 0.15 g of Scotch pine needles needles in a ratio of 1: 1, and the mixture was kept at 18-20 ° C for a day and administered orally to the scheme: day 1 at doses twice with 30 ml and 50 ml; 2 days three times in a dose of 100 ml; on the following days five times in a dose of 100 ml until clinical recovery (see US Pat. RU No. 2381806, IPC A61K 36 00. A61K 35/66, publ. 02.20.2010).

The disadvantage of this drug is that it does not have a pronounced antiviral activity, as well as the need for its long-term use in treatment.

A sorbent is known for the method for the prevention and treatment of pig mycotoxicoses, which consists in adding a sorbent to the diet of animals with feed contaminated with mycotoxins, while the waste material demetallization and clarification of wine materials containing transition metal ferrocyanides and bentonite are used as a sorbent.

In the method, the sorbent is introduced into the diet of pigs in an amount of 1% of the diet per day based on dry matter or as part of a 25% additive to the premix (see US Pat. No. 2300204, IPC A23K 1/175, A61K 31/00, publ. June 10, 2007).

The disadvantage of this sorbent is that it does not have a pronounced antiviral activity.

Known premix for the prevention and treatment of mycotoxicosis of cattle and pigs, including dianetophenonyl selenide as an active principle. beta-carotene, vitamin E, vitamin C, dissolved in vegetable oil, while it additionally contains vegetable phospholipids and wheat bran in the following ratio of components, mass. %:

diacetophenonyl selenide 0.001-0.01 beta carotene 0.001-0.01 vitamin e 0.01-0.02 plant phospholipids 0.1-0.2 vitamin c 0.01-0.02 vegetable oil 29.0-31.0 wheat bran rest

In a method for producing a premix, including dissolving diacetophenonyl selenide, beta-carotene, vitamin E, vitamin C in vegetable oil, vegetable phospholipids are first dissolved at a temperature of 105-110 ° C for 30-40 minutes, then the remaining components, after which the resulting the solution is applied to wheat bran (see US Pat. RU No. 2496329, IPC A23K 1/16, publ. 10.27.2013).

The disadvantage of this premix is that it does not have a pronounced antiviral activity, as well as the need for its long-term use in treatment.

The closest in technical essence and the achieved positive effect and adopted by the authors for the prototype is a preparation containing humic acid included in the feed for the prevention and treatment of calf mycotoxicosis (see S. Abakin S. Use of humic acids for the prevention and treatment of calf mycotoxicosis / C. S. Abakin, A.A. Grekova, A.N. Maltsev // Actual problems of the veterinary pharmacology of toxicology and pharmacy: materials of the III Congress of Pharmacologists and Toxicologists of Russia (St. Petersburg, June 8-10, 2011) St. Petersburg - 2011 .

The disadvantage of this drug is that it does not have a wide spectrum of action against mycotoxins (T-2 toxin, deoxynivalenone, zearalenone, fumonisin, ochratoxin).

Disclosure of the invention.

The objective of the invention is to develop a drug for the prevention of mycotoxicosis of small cattle, which has a wide spectrum of activity against mycotoxins (T-2 toxin, deoxynivalenone, zearalenone, fumonisin, ochratoxin), which is more economical when feeding animals in farms that do not have full guarantee feeding, free of mycotoxins feeds or when forced to use in feed diets with reduced quality, while the product is based on humic acids adding particulate silica, selenium, taken in nanoscale zero valent state and vitamin E and water distilled.

The technical result, which can be achieved using the present invention, boils down to a wide spectrum of action against mycotoxins (T-2 toxin, deoxynivalenone, zearalenone, fumonisin, ochratoxin) and cost-effectiveness.

The technical result is achieved using a preparation for the prevention and treatment of mycotoxicosis of small cattle, including humic acids, while it is additionally equipped with finely divided silica, selenium taken in a nanoscale state and zero valency, fat-soluble vitamin E and distilled water, in the following ratio of components, masses . %:

humic acids 10.0-15.0 fine silica 40.0-50.0 selenium (Se ⁰ ) 0.01-1.0 vitamin e 5.0-10.0 distilled water rest

Thus, in addition to gastrointestinal diseases of a bacterial nature, disorders of the gastrointestinal tract can be caused by poisoning by mycotoxins (T-2 toxin, deoxynivalenone, zearalenone, fumonisin, ochratoxin).

Mycotoxins, metabolites of microscopic fungi, are ubiquitous and cause spoilage of food and feed. Many of them are dangerous potent toxic compounds for humans and animals. The damage caused by mycotoxins to the agro-industrial complex is extremely large. The most dangerous and toxic mycotoxins include T-2 toxin and aflatoxins. Mycotoxin poisoning is primarily manifested by a disturbance in the functioning of the organs of the gastrointestinal tract, dyspepsia, gastritis, impaired liver function, hemorrhages in the internal organs, etc. The disease is accompanied by a general depressed state of the animals, a decrease in appetite up to complete rejection of food, thirst, vomiting, and violation intestinal motility, an upset in the work of the cardiovascular system, shortness of breath, etc.

Contaminating livestock and crop products (rough crops), mycotoxins (T-2 toxin, deoxynivalenone, zearalenone, fumonisin, ochratoxin) can be dangerous to human health. Getting into the human body with food, including bread, mycotoxins exhibit mutagenic, carcinogenic, immunosuppressive effects, cause allergoses, damage to the liver and kidneys, and organs of the reproductive system.

, гербициды

, различные мутагены

, моноароматические

и полициклические ароматические соединения

, минералы

и микроорганизмы (Bacillus subtilis)

. Несмотря на это, гуминовые кислоты никогда не использовались в качестве адсорбента микотоксинов. Имеются отдельные работы, показывающие, что гуминовые кислоты in vitro могут связывать деоксиниваленол (ДОН) и зеараленон

, et al., 2007]. Получены также данные, показывающие способность гуминовых кислот (оксигумат) адсорбировать афлотоксин B1, причем эффекты оксигумата превосходили эффекты введения в рацион пивных дрожжей [С. Jansen van Rensburg et al, 2006], авторами с 2008 года проводятся работы по изучению возможности использования гуминовых веществ, для профилактики и лечения микотоксикозов сочетанной этиологии [Грекова А.А., Мальцев А.Н., 2008-2013].Prevention of mycotoxin poisoning is mainly associated with the prevention of mycotoxin ingress into animals, i.e. the identification of their content in feed and subsequent disposal (Ivanov D.V. Mycotoxicosis of animals (etiology, diagnosis, treatment, prevention) / A.V. Ivanov M.Ya. Tremasov, K.Kh. Papunidi, etc. - M .: Kolos , 2008. - 140 p .; Ivanov A.V. Mycotoxicoses (biological and veterinary aspects) / A.V. Ivanov, V.I. Fisinin, M.Ya. Tremasov and others .-- M .: Kolos, 2010. - 392 s.), And with a lack of selenium and vitamin E in the animal organism, conditions are created under which the full realization of the genetic potential is impossible, while the activity of a number of enzymes decreases, disrupting processes of neutralization of hydroperoxides and lipid peroxides are developing, oxidative stress develops, which leads to disruption of almost all types of metabolism and the development of severe pathological conditions (see A. Kudryavtsev. Use of selenium in veterinary medicine. - Siberian and Far Eastern lands. - 1975, No. 10 . - p. 36-37). The basis of the drug are humic acids, which according to published data have demonstrated the ability to bind various substances, such as heavy metals

herbicides

various mutagens

monoaromatic

and polycyclic aromatic compounds

minerals

and microorganisms (Bacillus subtilis)

. Despite this, humic acids have never been used as an adsorbent of mycotoxins. There are separate works showing that humic acids in vitro can bind deoxynivalenol (DON) and zearalenone

, et al., 2007]. Data were also obtained showing the ability of humic acids (oxyhumate) to adsorb aflotoxin B1, and the effects of oxyhumate were superior to the effects of introducing brewer's yeast into the diet [C. Jansen van Rensburg et al, 2006], since 2008, the authors have been studying the possibility of using humic substances for the prevention and treatment of mycotoxicosis of combined etiology [Grekova A.A., Maltsev A.N., 2008-2013].

Based on the obtained data, a preparation was developed for the prevention and treatment of mycotoxicosis of small cattle based on humic acids. To extract humic acids from peat, the method of extraction with sodium pyrophosphate is used, the method of N.N. Bambalova [Yudina N.V., 1996, Bambalov N.N., 1998, Physics and chemistry of peat, 1989, Maryganova VV, 2003]. The humic acids thus recovered can be used for the production of medical and veterinary preparations.

To enhance the adsorption capabilities, finely dispersed silica was added (average particle size not more than 0.09 mm, specific adsorption surface not less than 150 m ² / g), it is recommended to use components in ratios of 3: 1, respectively (Table 1).

The essence of the drug for the prevention and treatment of small cattle mycotoxins is as follows.

For the prevention and treatment of mycotoxicosis of small cattle in farms where there is no full guarantee of feeding animals free of mycotoxins (T-2 toxin, deoxynivalenone, zearalenone, fumonisin, ochratoxin) as feed or when forced to use low-quality feed in diets, they introduce feed into feeds a preparation for the prevention and treatment of small cattle mycotoxicoses, including humic acids, while it is additionally equipped with finely divided silica, selenium taken in the nanoscale state and zero valencies, fat-soluble vitamin E and distilled water, in the following ratio of components, mass. %:

humic acids 10.0-15.0 fine silica 40.0-50.0 selenium (Se ⁰ ) 0.01-1.0 vitamin e 5.0-10.0 distilled water rest

The above preparation is administered, mixing, in a preparation prepared for feeding, respectively, in the amount of 1% of the diet or as part of a 25% supplement to the drug daily, for a period of 1 to 2 months. The above preparation in the ratio of components is respectively introduced into the diet at a dose of 0.5 g / kg of grain containing several types of mycotoxins within acceptable concentrations (MPC) and higher, which leads to a decrease in cost and an increase in the effectiveness of the prevention and treatment of animal mycotoxicoses.

Brief description of drawings and other materials

Table 1 gives the drug for the prevention and treatment of mycotoxicosis of small cattle. Comparative characteristics of the effectiveness of various ratios of the components of the drug (blood biochemical parameters M ± m, n = 6).

In table 2, also, Comparative characteristics of the effectiveness of various doses of the composition (biochemical blood parameters M ± m, n = 6).

The implementation of the invention

Examples of specific performance of the drug for the prevention and treatment of mycotoxicosis of small cattle.

Example 1: When eating grain (oats) affected by several types of mycotoxins in concentrations of T-2, the toxin is 1.04 mg / kg, deoxynivalenone is 0.05 mg / kg, zearalenone is 0.2 mg / kg, fumonisin is 0.15 mg / kg, ochratoxin 0.37 mg / kg for 1.5 months, leads to damage to internal organs, as evidenced by an increase in serum activity of "marker" enzymes. There is an increase in serum activity of aspartate aminotransferase (AcAt) and alanine aminotransferase (AlAt) compared with the control. The de Rittis coefficient (ratio of activity of AcAT / AlAT) decreases in this case (Table 1), which also indicates serious liver damage. So, high transaminase activity is observed with hepatic cell necrosis, when enzymes enter the bloodstream. A prolonged increase in transaminase activity or an increase in activity in the later stages indicates the development of massive hepatic necrosis. The excess of AcAT activity over AlAT occurs due to the exit of the mitochondrial fraction. In our case, when eating grain affected by mycotoxins, there is a three-fold excess of serum AlAT activity compared to the control. This is characteristic of acute and chronic damage to liver cells, hepatitis and extrahepatic obstruction of the bile ducts.

A significant increase in the content of malondialdehyde (MDA) in the blood is observed compared with the control (Table 1), which corresponds to published data. It has been shown that mycotoxins activate lipid peroxidation in the liver and in tissues of other organs [Khachatourians G.G., 1990; Mezes M. et al., 1999]. Introduction to the diet of rats mycotoxins DON and T-2 toxin leads to the activation of LPO by 21 and 28%, respectively [Rizzo A.F. et al., 1994].

LPO activation, as a rule, leads to a decrease in antioxidant protection. In this experiment, an increase in catalase activity and a decrease in the content of antioxidant vitamins E and A in the blood of experimental animals are observed (Table 1).

Activation of free radical processes leads to a violation of the micro- and macro-rheological properties of blood. So, as a result of eating feed affected by mycotoxins, the acid resistance of red blood cells increases, as evidenced by a decrease in the percentage of hemolysis of red blood cells (Table 1). An increase in red blood cell resistance during mycotoxicosis is associated with structural changes in the membranes of red blood cells. The data obtained show an increase in cholesterol in the blood of experimental animals (table. 1).

When mycotoxins enter the body, protein and lipid exchanges are disrupted. There is a decrease in the content of total protein, albumin and γ-globulins and increases the content of cholesterol and LDL.

For the prevention and treatment of mycotoxicosis of small cattle, grain contaminated with several types of mycotoxins is mixed with the preparation according to the invention in the following ratio of components, mass. %:

humic acids - 8.0; fine silica - 35.0; selenium (Se ⁰ ) - 0.005; vitamin E - 3.0; distilled water - the rest.

Result: with this ratio of components there is an insufficient decrease in mycotoxins when introduced into the feed of the preparation according to the invention.

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

humic acids - 10.0; fine silica - 40.0; selenium (Se ⁰ ) - 0.01; Vitamin E - 5.0; distilled water - the rest.

Result: at this ratio of components, the damaging effect of mycotoxins on the digestive organs is excluded, as evidenced by a decrease in the serum activity of AcAT and AlAT (Table 1). The LPO process is effectively reduced, which is also evidenced by a significant decrease in the content of MDA, catalase activity and an increase in the content of antioxidant vitamins A and E. A decrease in the effect of the mycotoxin complex on metabolism is observed (Table 1).

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

humic acids - 15.0; fine silica - 50.0; selenium (Se ⁰ ) - 1.0; vitamin E - 10.0; distilled water - the rest.

When mixing grain contaminated with several types of mycotoxins in the above concentrations with the proposed drug, the damaging effect of the mycotoxin complex on the internal organs is eliminated and the metabolic processes are completely normalized (Table 1). In addition, the preparation according to the invention increases the content of bioelements in the blood, which also has a beneficial effect on metabolism and on the physiological status of the body. The content of erythrocytes, hemoglobin and CP increases (Table 1, 2).

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

humic acids - 18.0; fine silica - 55.0; selenium (Se ⁰ ) - 1.5; Vitamin E - 12.0; distilled water - the rest.

When mixing grain contaminated with several types of mycotoxins in the above concentrations with the proposed drug, the damaging effect of the mycotoxin complex on the internal organs is also eliminated and the metabolic processes are completely normalized. In addition, the preparation according to the invention increases the content of bioelements in the blood, which also has a beneficial effect on metabolism and on the physiological status of the body. The content of red blood cells, hemoglobin and CP increases, but the cost of the drug increases significantly.

Thus, examples 2 and 3 are the most optimal. The preparation is a complex compound, contains both organic and inorganic substances with adsorption ability, which provides physical and chemical methods of protection against toxic substances, while humic acids contain functional active groups and are able to interact with mycotoxins of various chemical structures, in contrast to well-known adsorbents (activated carbon or certain silica s and clay minerals) which lie on mucous compact conglomerates, humic acids freely slip between the villi of the intestinal epithelium and penetrate between epithelial cells wherein protect these sensitive tissues from damage. Thiol, diene, quinone and other groups of humic acids are able to interact with free radicals and thereby exert antioxidant effects on the body contained in the composition of humic acids in the form of complexes of trace elements (Zn, Se, Mn, etc.) are coenzymes of antioxidant enzymes (superoxide dismutase , catalase, glutathione peroxidase, etc.), which enhances the antioxidant effects of the drug, since the adsorption of humic acids includes not only physical but also chemical interactions, the formation of complex and ion exchange, it proceeds more intensively and dynamically compared to conventional inorganic adsorbents, and humic acids can significantly reduce the incidence of diarrhea and other digestive disorders, and also help to avoid excessive loss of water through the intestines during diarrhea. A well-known example is the “medical lignin” or polyphepan sorbent widely used in clinical practice.

The drug, including humic acids, finely divided silica, selenium (Se ⁰ ), taken in the nanoscale state, and of zero valency, fat-soluble vitamin E and distilled water the rest, has a high antibacterial activity. It was found that polyphenolic compositions based on humic substances have antimutagenic and antiviral effects. Humates are also recommended for the treatment of metabolic disorders in the digestive system. In this case, there are no side effects and complete elimination of the drug from the body. Humic acids are an environmentally friendly component based on natural biopolymers, do not have toxic and other harmful effects, and are used as part of agents that increase the body's resistance to various adverse factors. The mechanism of action of humic acids cannot be reduced to one function and can be complex when there are several different directions, and the effect is determined by a certain resultant. Adding finely divided silica to the preparation increases the adsorption capacity. Fine silica, being a balas substance, affects the rate of gastric emptying, the intensity of absorption in the small intestine, and the total transit time of the food through the gastrointestinal tract, which improves digestion, while hypomicroelementoses occupy a significant share in the structure of non-communicable animal diseases, and one of the most deficient trace elements are selenium and vitamin E, which provide the activity of redox enzymes and vitamins, immunological resistance, as well as antioxidant antenna defense of the body, its lack causes toxic liver dystrophy, growth depression and other pathologies. The selenium deficiency of the body is largely due to the low content of this trace element in soils. The uneven distribution of selenium in soil and water causes its different concentration in plants of different climatic zones. A certain correlation has been established between the content of selenium in soil and fodder plants on the one hand and the animal organism on the other. The drug provides a reduction in production costs, is convenient to use, can reduce the incidence of young farm animals, increase safety and reduce the cost of preventive measures.

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

- has pronounced antagonistic properties in relation to a wide range of pathogenic and opportunistic microorganisms that cause intestinal dysbiosis (salmonella, shigella, Escherichia, Klebsiella, staphylococcus, microscopic fungi);

- neutralizes mycotoxins by producing enzymes that destroy mycotoxins and their sorption by the components of the cell wall;

- also reduces the incidence of diarrhea, a nonspecific symptom of mycogoxicosis resulting from the inhibition of normal microbial growth by mycotoxins;

- allows to reduce the incidence of young farm animals;

- allows you to increase the safety and reduce the cost of preventive measures;

- provides a reduction in production costs;

- convenient to use.

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Claims (2)

A preparation for the prevention and treatment of small cattle mycotoxicoses, including humic acids, characterized in that it is additionally equipped with finely divided silica, selenium taken in a small size and zero valency, fat-soluble vitamin E and distilled water, in the following ratio of components, wt.%: humic acids 10.0-15.0 fine silica 40.0-50.0 selenium (Se ⁰ ) 0.01-1.0 vitamin e 5.0-10.0 distilled water rest

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