Study of compatibility of components of a new combined drug for treatment of alcoholic intoxication and its hepatoprotective effect on a model of alcoholic liver injury

Olha Rudakova,Tatiana Briukhanova,Nataliia Smielova,Elena Bezchasnyuk,Victoriya Georgiyants,Nataliia Bevz,Svitlana Gubar,Dmytro Lytkin

doi:10.15587/2519-4852.2021.249880

Olha Rudakova, Tatiana Briukhanova + Show 6 more

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https://doi.org/10.15587/2519-4852.2021.249880

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Abstract

The aim of the work is the development of a combined drug for use in alcohol intoxication based on the physicochemical properties and chemical compatibility of active pharmaceutical ingredients and excipients, and the study of the hepatoprotective effect in alcoholic hepatitis in rats. Materials and methods. During the studies, physical and physicochemical methods were used, a Specord 200 spectrophotometer (Germany), analytical scales Sartorius (SARTORIUS, Germany), class A volumetric glassware and reagents that meet the requirements of the State Pharmacopoeia of Ukraine (SPhU). Alcoholic hepatitis in rats was reproduced by intragastric administration of an aqueous 40% ethanol solution at a dose of 7 ml/kg for 1 week. Results. A new combined agent is proposed for use in alcohol intoxication in the form of an effervescent powder for the preparation of an oral solution, which contains glycine, L-glutamic acid, acetylsalicylic acid, ascorbic acid, fructose / sorbitol and sodium bicarbonate and citric acid to accelerate the dissolution of medicinal substances. To study the compatibility of the components, experimental studies of hygroscopicity, chemical interaction / chemical stability and an assessment of the redox potential of the proposed active pharmaceutical ingredients were carried out. To study the stability of the API, studies were carried out on sugaramine condensation due to the choice of amino acids and ascorbic acid in the composition of drugs. Based on the research results, it was decided to divide the API into 2 packages, separating sodium bicarbonate and glycine, which can interact with ascorbic acid / acetylsalicylic acid and ascorbic acid, respectively. In an in vivo experiment, it was found that the use of the new drug is accompanied by the normalization of the antioxidant-prooxidant status of the liver due to a likely decrease in the TBA-AP level and an increase in the RG index in the liver homogenate relative to the control group. Conclusions. Evaluation of the physicochemical properties of API allowed us to propose a new combined drug (TS-PP) for use in alcohol intoxication in the form of an effervescent powder for the preparation of oral solution. In alcoholic hepatitis in rats, it was found that the use of the studied drug largely prevents the formation of the effects of the toxic effects of ethanol on the rat organism, which is manifested by inhibition of destruction of hepatocyte membranes, a decrease in the level of LPO products, restoration of the RG index and improvement of the protein synthesizing function of the liver due to the complex effect of amino acids and ascorbic acid contained in the product

Highlights

According to the World Health Organization, epidemiological data on alcohol abuse worldwide remain disappointing: 3.3 million premature deaths (5.9 % of total deaths) each year are caused by excessive ethanol consumption
Studies of the chemical compatibility of the components were performed by the method of absorption spectrophotometry in the UV region of the spectrum
Theoretical substantiation of active pharmaceutical ingredients (API) The composition of the new combined drug (TSPP) for the elimination of alcohol intoxication was theoretically modelled and experimentally substantiated on the basis of obtained data to study the chemical compatibility of API and excipients, respectively, and hepatoprotective effect of the combination

Summary

Introduction

According to the World Health Organization, epidemiological data on alcohol abuse worldwide remain disappointing: 3.3 million premature deaths (5.9 % of total deaths) each year are caused by excessive ethanol consumption. Hangover syndrome is one of the most common conditions caused by excessive episodic or regular chronic alcohol consumption [3]. It should be noted that the high medical and social significance of the hangover syndrome is due to the negative impact on human health, and to the reduction and/or short-term disability, potential danger of driving a car or technical devices, etc. It should be noted that drugs to eliminate the hangover syndrome should be a means of symptomatic therapy, and to comprehensively affect the pathological condition, preventing its burden and the development of complications, especially from the hepatobiliary system [6]

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