RU2409556C1 - Method for synthesis of organic compound, preventing development of stress reactions in animals - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of an oxyglycine lithium salt of formula NH₂-CH(OLi)-COOLi, which can be used in veterinary and animal husbandry to prevent development of stress reactions in animals. The method involves mixing oxyglycine with lithium hydroxide in form of aqueous solutions and distillation at temperature 45°C in a vacuum rotary evaporator until a paste-like mass is obtained, from which the end product is extracted by washing with ethyl alcohol and drying in a desiccator.

EFFECT: obtaining the desired product with high output.

2 dwg

Description

The invention relates to agriculture, in particular to veterinary medicine, and can be used in pharmacology, medicine and animal husbandry, in particular for parenteral administration and in the diets of animals and birds to prevent the harmful effects of stress factors of any etiology on the body in order to increase their stress -stability, productivity, reducing the cost of feed for production and improving the quality of livestock products.

The introduction of intensive industrial technologies for the production of livestock products is often associated with the emergence of contradictions between the biological and technological aspects of the same problem. Facilitating the working conditions, a person often makes the living conditions of animals less comfortable. There are a number of new stressors. An absolute consequence of the stresses of any etiology is the excessive formation of free radicals, which adversely affects the metabolism, and consequently, the health of animals, their productivity, quality of products and the cost of its production.

The prior art knows a large number of all kinds of neurotropic substances for humans and animals. These biologically active substances are designed to prevent, mitigate and eliminate the effects of stressful effects on the body. They are designed to help the animal normalize responses to inadequate stimuli that initiate metabolic abnormalities that go beyond the fluctuations of the natural biological parameters of dynamic homeostasis. All these substances of various nature are mainly products of chemical synthesis. All of them, to a greater or lesser extent, are alien to a living organism, all of them are far from indifferent to animal health, almost all of them cannot be used in the production of environmentally friendly food for humans (Fomichev Yu.P. Beef biotechnology. M. : Rosselkhozizdat, 1984. - 238 pp., Baidevlyatov AB, Nikolaenko VP Prevention of stress of movement and veterinary treatments of poultry. Scientific and technical bulletin. Kharkov. (BUT Ukraine. Research Institute of Poultry). - 1983. - No. 15 . - p. 37-39., Afanasyeva A.I., Oguy V.G., Myakush to N.V., Taranenko V.N. Technological methods for adaptive methods of calf rearing (Barnaul, AGAU, 2006, 319 pp.).

The present invention is aimed at solving the technical problem of the synthesis of substances, on the basis of which it is possible to develop a new, more physiological way of dealing with any form of stress by preventing the development of stress reactions or to mitigate and eliminate the consequences, if the reaction to the stress factor could not be prevented, in agricultural animals and birds of various species and different age and gender groups.

The motive for creating lithium salt of oxyglycine is the need to search for new, more advanced drugs and, based on them, to develop new, more effective ways to increase stress resistance, non-specific resistance, productivity of farm animals and poultry, improve the quality of products, reduce the cost of feed, labor and financial funds for its production.

The essence of the author’s working hypothesis is as follows: gamma-aminobutyric acid (GABA) is one of the main natural mediators of inhibition in the central nervous system of all higher animals. Excitability, nervousness, sensitivity of animals and humans to stress are primarily associated with this acid. Difficulties arise due to the fact that the GABA molecule is a typical zwitterion, and due to its pronounced polarity and hydrophilicity, under normal conditions, it practically does not penetrate the blood-brain barrier and acts mainly either peripherally or directly in the synthesis sites (Sytinsky I.A. Gamma -aminobutyric acid - a mediator of inhibition. Leningrad. Nauka, 1977. - 139 p.).

In search of GABA analogues that can penetrate the blood-brain barrier and have a predominantly central effect, medicine in the late sixties of the last century focused on gamma-hydroxybutyric acid, which in the experiment and clinic showed a clear hypnotic, tranquilizing and antihypoxic effect. In the form of sodium salt, the drug, called sodium oxybutyrate, has been widely used in surgery, anesthesiology, ophthalmology, neurology and psychiatry (Zakusov V.V., Ed. Sodium oxybutyrate. Neuropharmacological and clinical research. M: Medicine, 1968, p. 134). A valuable property of sodium oxybutyrate was its ability to enhance the effect of narcotic and analgesic substances, to exert antihypoxic and antitoxic effects. In psychiatric practice, the tranquilizing and hypnotic effects of the drug are used.

A few years later in medicine, lithium salt of gamma-hydroxybutyric acid was clinically used as a psychotropic drug. (Lyubimov B.I., Tolmacheva N.S., Ostrovskaya R.U., Mitrofanov B.C. Experimental study of the neurotropic activity of lithium oxybutyrate. Pharmacol. And toxicol., 1980, 43, 395-401). Pharmacological and clinical studies of the drug showed that its effect is not a simple sum of the effects of lithium cation and oxybutyrate anion, but is characterized by its own spectrum, combining the antimaniacal effect of lithium with the tranquilizing effect of gamma-hydroxybutyric acid. The effect of lithium in this case is enhanced due to greater accumulation in the brain tissue, which allows it to be used in smaller doses. In medical practice, the drug exhibits a distinct prophylactic effect in depressive conditions, while having its own sedative effect.

Not limited to this, more than twenty years ago, the first attempts were made to use carbonyl reagents — hydroxylamine and aminoacetic acid (glycine) as inhibitors of GABA transamination. The theoretical justification for these attempts was that such compounds are able to interact with the aldehyde group of the pyridoxalphosphate and thereby inhibit GABA transferase, which catalyzes the main pathway for GABA degradation in the body. Pyridoxalphosphate is a cofactor of GABA transferase. The effect of oxyglycine on the inhibition of this pyridoxal enzyme was well expressed and did not weaken even in the presence of an excess of pyridoxalphosphate. After these observations, oxyglycine was tested in the clinic as an anticonvulsant in children, where in a number of cases it found a positive effect (Raevsky KS, Georgiev VP Mediator amino acids, M .: Medicine, 1986. p.239). Naturally, on the basis of this knowledge, it was postulated that oxyglycine can take a significant place as a means for inhibiting GABA transferase with the aim of a subsequent increase in the concentration of GABA in the brain.

It is known from the prior art that lithium mineral salts also have nootropic (psychotropic) properties, while they freely cross the blood-brain barrier and penetrate the brain (Schow M. Lithium studies. Acta Pharmacol. ToxicoL, 1998. 45 (2): 115- 124). Therefore, it was logical to assume that with the introduction of oxyglycine in combination with lithium, GABA will decompose more slowly, it is easier to overcome the blood-brain barrier and its concentration in the brain will increase. In turn, an increase in the concentration of GABA, based on knowledge of its physiological effect, will entail a simultaneous decrease in the excitability of animals with an increase in stress resistance.

Based on these data, we can say that the specific goal of creating a complex lithium compound with oxyglycine is the need to obtain such a compound that will be able to exhibit a more physiological and higher positive effect than occurs when animals separately use lithium and oxyglycine.

The applicant synthesized a new compound absent in the country and in the world - an organic lithium salt with oxyglycine. Both components used for the synthesis of a new organic salt (lithium mineral salt and oxyglycine) are legally approved for use in medical practice.

In the patent and scientific literature there is no description of the method for the synthesis of lithium salt of oxyglycine. This circumstance allows us to consider the claimed invention patentable as meeting the condition of patentability "inventive step". (Part Four of the Civil Code of the Russian Federation No. 230-FZ of 12/18/2007).

The proposed synthesis method is general and based on the chemical properties of the starting components (lithium oxide hydrate and oxyglycine), on the ability of alkaline earth metals, in particular lithium, to interact with amino acids and form stable compounds, in particular the lithium salt of oxyglycine.

The method of synthesis of lithium oxyglycinate (organic lithium salt with oxyglycine)

Starting materials

We used lithium sulfate (Li ₂ SO ₄ ), sodium hydroxide (NaOH), potassium hydroxide (KOH), hydroxyaminoacetic acid (oxyglycine), ethyl alcohol (98%). All reagents brand XC.

A weighed portion of lithium sulfate salt weighing 90 g is dissolved in 100 ml of distilled water to obtain a clear solution saturated at a temperature of 40 ° C according to solubility data [Brief chemical reference book of V. A. Rabinovich, 1978, 316 pp.]. After dissolution, it is controlled that the pH of the solution is 7. To this solution, weighed portions of sodium hydroxide weighing 50 g and potassium hydroxide weighing 50 g are added. As a result of the substitution reaction, a white precipitate of lithium oxide hydrate precipitates. The precipitate formed is filtered off from the supernatant on a glass filter under vacuum. The resulting white lithium hydroxide powder was washed with ethanol (98%) and transferred to a desiccator until it was completely dry. Next, a sample of dried lithium hydroxide weighing 60 g is dissolved in 250 ml of distilled water at a temperature of 25 ° C. In this case, the solution acquires a pH value of 10. A 50 g sample of oxyglycine is dissolved in 100 ml of distilled water. Both solutions are poured into a round bottom flask, placed in a water bath at a temperature of 45 ° C and distillation is carried out using a rotary evaporator under vacuum (P = 97 Pa). Within 6.5 hours, a precipitate forms. The resulting pasty mass of white is transferred onto filter paper placed in a glass filter, washed with ethanol (98%) and placed in a desiccator until it is completely dry. Obtain 55.3 g of dry matter, which is the final, desired product.

Thermogravimetric analysis of the samples was carried out on a NETZSCH STA Jupiter 449 C instrument (Figure 1), combined with a Fourier-IR spectrometer. The infrared spectrum of the compound (Figure 2) has vibrational bands corresponding to the bonds of primary nitrogen, an ether linkage, which confirms the structure of the molecule and the given formula. This conclusion is confirmed by elemental analysis performed using the Vario EL Micro- and macro CHNOS Elemental Analyzer.

Basic physico-chemical parameters of lithium oxyglycinate

Nomenclature name - Lithium salt of aminooxyacetic acid

The empirical formula is NH ₂ -CHOLi-COOLi

Gross formula C ₂ H ₃ O ₃ NLi ₂

Elemental composition in percent:

C - 22.8, H - 1.9, O - 45.7, N - 13.3, Li - 13.3

Melting point - 198.7 ° C

Decomposition temperature - 220.4 ° С

Soluble in water-alcohol mixtures and water.

Harmless to animals - withstands the test, belongs to the third hazard class according to GOST 12.1. 007-76.

Claims (1)

A method of obtaining a lithium salt of oxyglycine of the formula NH ₂ -CH (OLi) -COOLi, which consists in the fact that oxyglycine is combined with lithium oxide hydrate in the form of aqueous solutions and distillation is carried out at a temperature of 45 ° C in a vacuum rotary evaporator to obtain a paste from which the desired product is isolated by washing with ethyl alcohol and drying in a desiccator.

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