TOXICITY STUDY OF MOISTURIZING ANTIXEROSTOMY GEL DURING SINGLE ADMINISTRATION
Authors:   Altai State Medical University, Mazko Olesya N. , Vorobyeva Valentina M. ,   Altai State Medical University, Shishkina Oksana E. ,   Altai State Medical University, Semennikova Nina V. ,   Altai State Medical University, Leskova Svetlana S. ,   Altai State Medical University, Kalnitsky Artem S. ,   Altai State Medical University, Gossen Ivan E. ,   Altai State Medical University, Shoykhet Olga V. ,   Altai State Medical University
Published: December 2024

Introduction. In clinical practice, xerostomia, or dry mouth (ICD 10 - K 11.7), is a chronic disease that usually develops against a background of hyposalivation, when salivary secretion is reduced to 50-60%, but can also occur with normal salivary secretion, but with a violation of ratio of components of the salivary gland secretion. The causes of xerostomia are due to many medical problems and factors. Xerostomia syndrome complicates the development of dental diseases, leads to tooth loss, which ultimately significantly reduces the quality of life of patients. Regardless of the cause of the development of xerostomia, patients need substitution therapy with artificial saliva preparations. To expand the range of products for dental practice and import substitution, we have developed a saliva substitute composition in the form of a moisturizing gel based on mucoadhesive polymers. One of the requirements for new drug formulations in the context of preclinical studies is the absence of “acute” and chronic toxicity.

Objective. To evaluate the toxicity of antixerostomy moisturizing gel by single administration in mice and rats.

Materials and methods. The object of the study was a gel composition of saliva substitute based on mucoadhesive polymers and a complex of biologically active substances, including lysozyme, pyridoxine hydrochloride, and tocopherol acetate. As part of preclinical drug studies, the toxicity of the experimental gel was studied during single administration. During the experiment, the drug was administered intragastrically through a probe at a minimum dose of 2000 mg/kg, which is recommended for safety studies of non-toxic compounds. The total duration of observation of the animals was 14 days. In the first 24 hours the observation was carried out continuously. Evaluation of ‘acute’ toxicity at a single administration was carried out according to the GLP rules according to the following criteria: number of dead animals and terms of their death; general clinical picture of intoxication; changes in behavioral reactions.

Results. After a single intragastric administration of the saliva substitute gel at a dose of experimental animal 2000 mg/kg, no cases of death were recorded. No clinical manifestations of intoxication and changes in animal behavior were also not observed. When studying the dynamics of body weight of experimental animals, it was found that during 14 days of the observation period there was a clear tendency to increase body weight of mice and rats of both sexes.

Conclusion. No cases of death of experimental animals (mice, rats) were recorded during the toxicity evaluation in a single oral administration of moisturizing antixerostomy gel at a dose of 2000 mg/kg. The clinical manifestations of intoxication were not revealed. The research object (moisturizing antixerostomy gel) is a low-toxic substance that can be referred to the IV class of hazard- low-toxic chemicals.