Investigation of anti-inflammatory and antipyretic activity of polymorphic modification of n-(trifluoromethylphenyl)-4-hydroxy-2,2-dioxo-1h-2λ6,1-benzothiazine-3-carboxamide derivative in rats

Abstract

Annotation. Polymorphism among biologically active substances is an extremely important factor that modifies the therapeutic properties of pharmaceutical substances and dosage forms, significantly affects the parameters of their biological activity and pharmacokinetics. Chemical synthesis among the derivatives of 4-R-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acids gave the leader compound N-(4-trifluoromethylphenyl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide, the crystalline polymorph of which in the form of plates has a pronounced analgesic activity. The aim of the study was to investigate the anti-inflammatory activity of compound B by its effect on various components of the inflammatory reaction, as well as the antipyretic effect of this compound in rats. The anti-alterative activity was determined on the model of planar skin wounds, the antiproliferative effect - on the model of cotton granuloma, the anti-exudative effect - on the model of toxic pulmonary edema in rats. The antipyretic effect was studied in a model of milk fever in rats. The study was performed on 91 white male Wistar rats. Statistical processing of the obtained results was performed using the program "STATISTICA 6.1" by methods of variation statistics using parametric and nonparametric methods. The results showed that the polymorphic compound B has anti-inflammatory activity on all components of the inflammatory reaction - alteration, exudation and proliferation. In terms of efficacy in the model of experimental inflammation, this substance is superior to meloxicam, as its ED50 when administered orally is 5.2 mg/kg, while the reference drug - 9.1 mg/kg. Compound B exhibits a pronounced antipyretic effect in a rat fever model. Therefore, the polymorphic modification of the carboxamide derivative in the form of plates is promising for further research in order to create on its basis a drug with analgesic, anti-inflammatory and antipyretic properties.