Research Results in Pharmacology 3(2): 101-111, doi: 10.18413/2313-8971-2017-3-2-101-111
NEW DOSAGE FORM OF L-ARGININE BASED ON ITS COMPLEX WITH CELLULOSE ACETATE SULFATE AND ACTIVATED CARBON
expand article infoEkaterina A. Shakhno, Tatyana Alexandrovna Savitskaya, Tatyana Grigoryevna Pokrovskaya, Vladimir I. Yakushev, Dmitry D. Grinshpan
Open Access
Abstract
Introduction: The oral route of L-arginine intake, despite its great comfort, is less effective in comparison with infusions. The development of new pharmaceutical forms for oral preparation is of undoubted interest. Objectives: To obtain a new dosage form of L-arginine by complexation with sodium salt of cellulose sulfate acetate (Na-CSA) followed by immobilization on activated carbon, and to evaluate its endothelial, cardioprotective and antihypertensive activity. Methods: UV-, visible spectroscopy, FTIR spectroscopy, viscometry, molecular mechanics, animal experiments with male Wistar albino rats in the modeling of L-NAME-induced endothelium dysfunction. Results: The physicochemical parameters of complexation, the adsorption activity of activated carbons of various origins with respect to individual L-arginine and its complex with Na-CSA were investigated. The greatest amount of adsorption and its smaller difference between L-arginine and the complex were taken into account when choosing activated carbon as a carrier (AUT-MI: GL-Arginine=320.2±0.1 mg/g, Gcomplex=340.2±0.1 mg/g; OU-A: GL-Arginine=210.1±0.1 mg/g, Gcomplex=235.1±0.1 mg/g; TH-90G: GL-Arginine=190.1±0.1 mg/g, Gcomplex=190.2±0.1 mg/g). Release of L-arginine as a result of its desorption into the model media of the human body was higher (96.3±0.5 wt.%) for the alkaline medium of intestines than for the acidic medium of stomach (10.0±0.1 wt.%). In animal experiments, it was shown that a combined preparation of L-arginine complex immobilized at doses of 30 mg/kg, 70 mg/kg and 200 mg/kg exhibits a pronounced antihypertensive, endothelioprotecive and cardioprotective activity at a dose of 200 mg/kg with L-NAME-induced nitric oxide deficiency (p
Keywords
L-arginine, L-NAME, nitric oxide deficiency, water-soluble cellulose derivative, activated carbon, immobilized complex, dosage form, antihypertensive, endothelioprotecive and cardioprotective activity.