RU2438666C1 - Selenium-containing preparation for microelementosis prevention and treatment in farm animals and poultry - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns zoopharmacy. A selenium-containing preparation for microelementosis prevention and treatment caused by selenium deficiency in farm animals and poultry contains a stabiliser presented by high-molecular nitrogen-containing polymer 0.1-10.0%, nanosized selenium of null valency 0.0001-1.0%, fat-soluble vitamin E 1.0-20.0%, the molar ratio of vitamin E/selenium 5:1-50:1, a wedding agent 1.0-20.0% and water.

EFFECT: invention provides metabolic process activation and selenium deficiency correction in an animal's body.

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Description

FIELD OF THE INVENTION

The invention relates to veterinary pharmacy, in particular to preparations containing selenium in the nanoscale state, to increase the resistance of animals, can be used to regulate metabolic processes and reduce the frequency of selenium deficiency in animals.

Selenium is a biologically active essential trace element, is part of a number of hormones and enzymes, and plays a crucial role in the functioning of the immune system. Selenium compounds protect cell membranes from the effects of free radicals and prevent their generation, reducing the risk of tumors and the development of heart and blood vessel diseases.

At present, inorganic selenium preparations based on selenite and sodium selenate are most widely used to compensate for the deficiency of selenium in farm animals and birds, but their toxicity is high.

Organic selenium derivatives currently used, such as selenopyran, diacetophenonyl selenide (DAFS-25), dimethyldipyrazolyl selenide (selecor), Sel-Plex, Seledant and others, exhibit lower toxicity, but their cost is quite high.

The most promising is the use of nano-selenium - a form of selenium with a particle size of 20-60 nm. The main advantage of nano-selenium compared to other forms is its much lower toxicity, which allows it to be used in doses significantly exceeding the daily requirement. In addition, nanolin has a so-called size effect, which is manifested in the fact that nanoparticles are biologically more active and better accumulate in tissues.

State of the art

The literature contains information on a preparation containing selenium and water for injection (see Kudryavtsev A.P. Use of selenium in veterinary medicine. - Siberian and Far Eastern lands. - 1975, No. 10. - P.36-37).

The disadvantage of this drug is the poor digestibility of selenium and relatively high toxicity.

Known drug containing sodium selenite and vitamin E, which is successfully used for the prevention of postpartum diseases in cattle (Smith AM and Picciano M.F. Evidence for increased selenium requirement for the rat during pregnancy and lactation. - J. of Nutrition, 1986, v. H6, N6, p.1068-1079; Smith I., Hogan J. Vitamin E and selenium can help lover incident of mastitis. - Zarge anim. Veter., 1988, 43, 6, 20-24).

The disadvantage of this drug is also a lack of digestibility and high toxicity.

The closest in technical essence and the achieved positive effect and adopted by the authors for the prototype is a drug for the treatment and prevention of metabolic disorders of selenium for farm animals (application No. 2008137463 from 09/18/2008, publ. 03/27/2010), including selenium, a stabilizer and water for injection moreover, a high molecular weight nitrogen-containing polymer is used as a stabilizer, and selenium is taken in the nanoscale state and zero valence (Se ⁰ ). The disadvantage of this drug is the low digestibility and bioavailability of selenium.

Disclosure of invention

The task of the invention is to develop a comprehensive drug based on aggregatively stable nanoparticles of selenium in the zero degree of oxidation with a size of 20-60 nm and vitamin E.

The technical result that can be achieved using the present invention is to reduce toxicity, increase the antioxidant effect, increase the digestibility and bioavailability of selenium through the use of a complex preparation containing nanoparticles of nullvalent selenium with sizes from 20 to 60 nm and solubilized vitamin E.

The specified technical result is achieved due to the fact that in the preparation for the prevention and treatment of microelementosis in farm animals and birds, containing a stabilizer, which is used as a high molecular weight nitrogen-containing polymer; selenium taken in the nanoscale state and zero valency, and water for injection, according to the invention add fat-soluble vitamin E and a solubilizer in the following mass ratio of components,%: selenium (Se ⁰ ) 0.01-1.0; high molecular weight nitrogen-containing polymer 0.1-10.0; solubilizer 0.10-20.0; Vitamin E 0.01-10.0; water for injection - the rest; moreover, the molar ratio of vitamin E / selenium is in the range of 1: 1-50: 1.

The technical result is achieved subject to the conditions for the process of obtaining a complex preparation, namely:

- the use of an aqueous solution of nullvalent selenium nanoparticles with a concentration of 0.1-1.0% stabilized by a high molecular weight nitrogen-containing polymer as a selenium source;

- the use of Solutol HS-15 as a solubilizer;

- the use of alpha-tocopherol acetate as fat-soluble vitamin E;

- the molar ratio of vitamin E / selenium should be in the range of 1: 1-1: 50.

The essence of obtaining an aggregatively stable system containing selenium nanoparticles in the zero oxidation state and vitamin E is as follows.

Elemental selenium nanoparticles in the form of six-membered rings of various conformations, stabilized by macromolecules of a nitrogen-containing polymer (in particular polyvinylpyrrolidone), interact with particles of solubilized fat-soluble vitamin E to form an aggregatively stable system that does not delaminate during storage. The size of selenium nanoparticles in the resulting system does not exceed 60 nm.

The implementation of the invention

Examples of specific preparation of a complex selenium-containing preparation in the form of an aggregatively stable system containing selenium nanoparticles in a zero oxidation state and vitamin E.

Example 1

The drug is prepared by mixing in a chemical reactor an aqueous solution of nullvalent nanoselen stabilized by a nitrogen-containing polyelectrolyte with a solution of alpha-tocopherol acetate in a solubilizer, followed by ultrasonic treatment of the resulting system for sterilization and additional dispersion of the finished product, while taking the following ratios of components (in wt.% ):

Selenium 0.01 High molecular weight N-containing polymer 0.2 Solubilizer (SolutolHS-15) 1,0 Vitamin E 3.0 Water Rest Vitamin E / Selenium (mol / mol) 50: 1

The resulting complex selenium-containing preparation is packaged in a container by aseptic filling.

Example 2 (optimal)

The drug is prepared by mixing in a chemical reactor an aqueous solution of nullvalent nanoselen stabilized by a nitrogen-containing polyelectrolyte with a solution of alpha-tocopherol acetate in a solubilizer, followed by ultrasonic treatment of the resulting system for sterilization and additional dispersion of the finished product, while taking the following ratios of components (in wt.% ):

Selenium 0.10 High molecular weight N-containing polymer 2.0 Solubilizer. (Solutol HS-15) 10.0 Vitamin E 3.0 Water Rest Vitamin E / Selenium (mol / mol) 5: 1

The resulting complex selenium-containing preparation is packaged in a container by aseptic filling.

Example 3

The drug is prepared by mixing in a chemical reactor an aqueous solution of nullvalent nanoselen stabilized by a nitrogen-containing polyelectrolyte with a solution of alpha-tocopherol acetate in a solubilizer, followed by ultrasonic treatment of the resulting system for sterilization and additional dispersion of the finished product, while taking the following ratios of components (in wt.% ):

Selenium 1,0 High molecular weight N-containing polymer 20,0 Solubilizer .. (Solutol HS-15) 20,0 Vitamin E 6.0 Water Rest

Vitamin E / Selenium (mol / mol) 1: 1

The resulting complex selenium-containing preparation is packaged in a container by aseptic filling.

The results of toxicological studies of a complex preparation based on aggregatively stable nanoparticles of selenium in the zero oxidation state and vitamin B are shown in table 1.

For toxicological studies, clinically healthy white mice weighing 20-22 g were used. Studies were carried out according to the “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). The route of administration was parenteral, as This medication is intended for intramuscular administration to farm animals.

Table 1 Acute toxicity of complex preparations based on aggregatively stable nanoparticles of selenium in the zero oxidation state and vitamin E with a single intraperitoneal injection for white mice (mg / kg). Type of drug Toxicity parameters SLD ₅₀ MTD LD ₁₆ LD ₅₀ LD ₈₄ LD ₁₀₀ Example 1 12 fourteen 18.3 23.5 24.0 ± 0.16 Example 2 11,2 26.35 34.97 45.55 57.65 ± 0.04 Example 3 4.36 4.62 6.11 7.25 7.20 ± 0.02 Nanoselen (prototype) 10,2 25,4 33.0 44,2 56.4 ± 0.3

The results obtained indicate that the new dosage form of the selenium-containing preparation, according to its toxicological characteristics, is a low-hazard substance for warm-blooded animals and allows, in accordance with GOST 121.007-76, to classify it as hazard class IV and III, respectively.

The results of biochemical studies of complex preparations based on aggregatively stable selenium nanoparticles in zero oxidation state and vitamin E are shown in table 2.

table 2 Results of a biochemical analysis of rabbit blood Type of drug Enzyme activity The content of malondialdehyde,% Catalase in 14 days Peroxidase after 14 days Aspartate aminotransferase after 5 days Alanine aminotransferase after 5 days Example 1 0.56 ± 0.02 17.9 ± 7.4 1.70 ± 0.02 1.79 ± 0.11 1.48 ± 0.56 Example 2 0.95 ± 0.17 27.4 ± 3.6 2.21 ± 0.05 2.13 ± 0.08 0.75 ± 0.08 Example 3 0.48 ± 0.06 18.2 ± 2.8 1.95 ± 0.04 1.77 ± 0.63 1.22 ± 0.15 Nanoselen (prototype) 0.84 ± 0.08 25.1 ± 0.89 2.13 ± 0.17 1.95 ± 0.15 0.88 ± 1.32

To assess the effect of a complex preparation based on aggregatively stable selenium nanoparticles of zero oxidation and vitamin E on the body and increase in live weight, clinically healthy rabbits were used.

Table 3 Dynamics of live weight of rabbits after the use of a complex preparation based on aggregatively stable nanoparticles of selenium in a zero oxidation state and vitamin E at a dose of 0.025 mg / kg, kg Type of drug Before introduction After 8 days In 15 days In 23 days After 31 days Example 1 2.15 ± 0.1 2.25 ± 0.3 2.35 ± 0.2 2.44 ± 0.8 2.56 ± 0.4 Example 2 2.25 ± 0.1 2.40 ± 0.4 2,52 ± 0,1 2.62 ± 0.2 2.74 ± 0.1 Example 3 2.22 ± 0.2 2.37 ± 0.1 2.45 ± 0.4 2.55 ± 0.1 2.66 ± 0.1 Nanoselen (prototype) 2.20 ± 0.4 2.40 ± 0.3 2,50 ± 0,4 2.6 ± 0.4 2.7 ± 0.3

An analysis of the results indicates that the use of the drug contributes to the activation of the antioxidant defense system of the body, which is expressed in an increase in the activity of catalase, peroxidase and a decrease in the concentration of malondialdehyde in the blood, an under-oxidized product of free radical reactions.

In addition, there was an increase in live weight of rabbits when using a complex selenium-containing preparation in comparison with the prototype.

The invention in comparison with the prototype has the following advantages:

- reduction of toxicity;

- increase the antioxidant effect;

- higher digestibility, expressed in weight gain.

Claims (1)

Selenium-containing preparation for the prevention and treatment of microelementosis in farm animals and birds, containing a stabilizer, which is used as a high molecular weight nitrogen-containing polymer, selenium taken in the nanoscale state and zero valency, and water for injection, characterized in that it additionally contains fat-soluble vitamin E and solubilizer in the following ratio of components, wt.%:
selenium (Se ⁰ ) 0.01-1.0 high molecular weight nitrogen-containing polymer 0.1-10.0 solubilizer 0.10-20.0 vitamin e 0.01-10.0 water for injections rest,
moreover, the molar ratio of vitamin E: selenium is in the range of 1: 1-50: 1.