Kitosan Türevlerini İçeren Hidrojellerin ve Çözeltilerin Hemostatik Özelliklerinin Değerlendirilmesi
Elçi, Sıtkı Doğa
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The main aim of this thesis study is to synthesize the sponge and gel forms of chitosan derivatives which may be hemostatically active due to their structures, and to evaluate the hemostatic and antimicrobial activities of these derivatives. Within the scope of the presented thesis, raw chitosan was first purified by applying a strong base NaOH at 70°C. The FT-IR spectroscopy analysis revealed no significant differences between the transmittance spectra of the raw and the purified chitosan, i.e., the raw chitosan was free from protein contamination. The degradative effect of purification on raw chitosan was demonstrated by Size Exclusion Chromatography (SEC) analysis. Since insoluble impurities were also removed by vacuum filtration during the respective purification process, syntheses in the further stages of the study were made using purified chitosan. The protonation degrees of chitosan acetate (K-Ac) and chitosan citrate (K-Ci) salts of polycationic chitosan derivatives synthesized were calculated using potentiometric measurements. Another synthesis was a quaternized derivative of chitosan, N, N, N-trimethyl chitosan (TMK), whose polycationic property is independent of pH. The purity of TMK derivative was determined based on the correlations in Heteronuclear Single Quantum Correlation (1H-13C HSQC) and Heteronuclear Multiple Bond Correlation iv (1H-13C HMBC) spectra, and methylation degrees were determined by 1H NMR analysis. The degradative effect of the quaternization process on the pure chitosan used was demonstrated by SEC analysis. To determine the effect of the derivatization methods on the solubility of the chitosan main chain; % Transmittance at 25˚C and 500 nm of aqueous mixtures of samples containing 5 mg / ml chitosan main chain were measured by a UV/Vis spectrophotometer. As a result of the purification process, the solubility of the degraded chitosan in water increased as expected. It was determined that the solubility of purified chitosan was further increased due to protonation using acetic acid and citric acid. Although the degree of trimethylation of the TMK derivative was higher than the degree of protonation of the K-Ac, TMK turned out to be less soluble. In the context of molecular modeling studies, chitosan exhibited the potential of demonstrating agonist effects via the Glycoprotein IIb / IIIa thrombocyte receptor. Furthermore, the ability of chitosan to bind both to GPIIb / IIIa and fibrinogen, showed that chitosan could be effective in the clotting process by acting as the functional analogue of the Von Willebrand factor (vWF). As determined by molecular dynamics method, protonated chitosan and TMK oligomers may reinforce the coagulum via electrostatic interactions with the erythrocyte membrane. This effect was found to be lower in the TMK derivative. Polyvinyl Alcohol (PVA) / Polyvinyl Pyrrolidone (PVP) / glycerine / K-Ci and PVA / PVP / glycerine / TMK composite gels were also prepared. In antimicrobial efficacy test, TMK showed the highest efficacy. As determined in the in vitro efficacy test, Whole Blood Coagulation Time (WHBCT) was shortened in K-Ac, Chitosan and Gel groups compared to empty group, but prolonged in K-Ci group (p < 0.05).