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NEW DOSAGE FORM OF L-ARGININE BASED ON ITS COMPLEX WITH CELLULOSE ACETATE SULFATE AND ACTIVATED CARBON

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<0.05; 30 mg/kg: EDCL-Arginine=3.6±0.3; EDCcomplex=3.0±0.2; 70 mg/kg: EDCL-Arginine=2.7±0.1; EDCcomplex=2.3±0.2; 200 mg/kg: EDCL-Arginine=2.5±0.1; EDCcomplex=1.9±0.1). Conclusion: Due to the antihypertensive, endothelial and cardioprotective activity of L-arginine as a complex with Na-CAC immobilized on activated carbon, it is possible to obtain an effective dosage form (tableted or granulated) of L-arginine for oral use.

Иллюстрации

Fig. 1. 1- L-arginine; 2- Na-SAC

Fig. 2. The variation of reduced viscosity with concentration for Na-CAS and its complex with L-arginine solutions in 0.2M NaCl

Fig. 3. The FTIR spectra 1-complex Na-CAS-L-arginine; 2- Na-CAS; 3- L-arginine

Fig. 4.The fragment of the complex structure for two cellobiose units (2D and 3D models)

Fig. 5.  Maximum Gibbs adsorption value for L-arginine and its complex on AUT-MI, OU-A and TH-90G.

 Table 1. Specific surface area and pore structure characteristics of the applied activated carbons

Fig. 6. Adsorption isotherms of L-arginine and L- arginine -Na-CAS on the activated carbon AUT-MI at T = 298 K. 1- complex L-arginine – Na-CAS; 2-L-arginine.

Fig. 7. Limit values of adsorption, determined by the Langmuir equation G and experimental values Gmax, for different carbon materials

 Fig. 8. The Langmuir constant values for different carbon materials

Fig. 9. Surface tension isotherms of aqueous solutions at T = 298 K.

1 – Na-CAS; 2 – L-arginine; 3 – complex L-arginine-Na-CAS.

Table 2. The effect of new dosage form of L-arginine on hemodynamics values and EDC in modeling of L-NAME-induced endothelium dysfunction (M±m n=10)

 

Table 3. The effect of new dosage form of L-arginine on the left ventricle of rats’ heart contractility (M±mn=10)

DOI: 10.18413/2313-8971-2017-3-2-101-111
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