Synthesis And Properties Of Biomaterials Based On Chitosan Oligosaccharide

Chitosan oligosaccharide is a well-known abundant natural polymer with good biodegradability, biocompatibility and bioactivity. But the insolubility in common organic solvents and non-thermal plasticity of chitosan oligosaccharide have delayed its utilization and basic research. Chemical modification of chitosan oligosaccharide is more attractive to expand the applications as functional materials. Especially, it is promising and have great value of scientific reference to combine the chitosan oligosaccharide (CSO) having good hydrophilic property and bioactive functions with poly (ε-caprolactone) which has good mechanical properties and biodegradability, and liquid crystal monomers having bioactive cholesterol to generate new biomaterials based on chitosan oligosaccharide. These materials should be applicable for biodegradable material, drug delivery systems and tissue engineering.On the base of large related information retrieval research at home and abroad, in this dissertation, we have designed and synthesized two kinds of precursors of chitosan oligosaccharide derivatives, four kinds of biomaterials based on chitosan oligosaccharide through the modification of amino groups and hydroxyl groups of CSO. The purpose of it is to improve its poor solubility in organic solvents and the limits of non-processability because it has no melting point. Two kinds of precursors are phthaloyl chitosan oligosaccharide (PHCSO) and O,O-dilauroyl chitosan oligosaccharide (LCSO), respectively. Four kinds of biomaterials based on CSO are thermoplastic N,O-dilauroyl chitosan oligosaccharide (NOCSO-2), chitosan oligosaccharide-graft-poly (ε-caprolactone) with free active amino groups, thermoplastic phthaloyl chitosan oligosaccharide-g-polycaprolactone, and phthaloyl chitosan oligosaccharide-g-polycaprolactone-g-cholesterol respectively. As far as we know, the designed biomaterials based on chitosan oligosaccharide have never been reported, they are innovative. The chemical structure and physical properties of biomaterials based on chitosan oligosaccharide are confirmed by fourier transform infrared (FT-IR) spectra,1H nuclear magnetic resonance, differential scanning calorimetry (DSC), thermogravimetric analyse (TGA), polarizing optical microscopy (POM), scanning electron microscope (SEM), X-ray diffraction (XRD). The main contents and results list below:1. Through acylation modification of chitosan oligosaccharide, O,O-dilauroyl chitosan oligosaccharide (LCSO) was synthesized by the reaction of the hydroxyl group of chitosan oligosaccharide (CSO) and suitable count of lauroyl chloride via the amino groups protection procedure in homogeneous system of methane sulfonic acid. The solubility of LCSO had been improved in organic solvents. SEM indicated that the layer structure of CSO has been changed and the surface morphology of LCSO became crude. XRD and themoanalyses indicated that the original crystal structure of CSO did change with the lauroyl acylations and had created new crystal domains of lauroyl side chains. The decomposition temperature of LCSO is lower than that of CSO.2. On the basis of LCSO, N,O-dilauroyl chitosan oligosaccharide (NOCSO) with different substitution were synthesized through changing the mole ratio of lauroyl chloride to chitosan oligosaccharide to make the further reaction of amino group. The results showed that the intra hydrogen bonding of CSO was weakened and the original crystal structure of CSO did change through the introduction of long lauroyl side chains and had created new crystal domain of lauroyl side chains. When almost all the amino group and hydroxyl group were substituted, NOCSO has thermoplasticity and the decomposition temperature is 167.3℃. The grain structure aligned tightly and can be observed by POM.3. Phthaloyl chitosan oligosaccharide precursor (PHCSO) was synthesized via the amino groups protection of CSO with phthalic anhydride. The phthaloyl chitosan oligosaccharide-g-polycaprolactone (PHCSO-g-PCL) was synthesized by coupling the hydroxyl group via the ring-opening graft copolymerization ofε-caprolactone in the presence of stannous octoate catalyst. The regioselective graft modification of CSO can be done through this method of graft polymerization, and the free amino group can be abstained through removing the protective group by hydrazine. It was found that the graft content of PCL within the graft copolymer increased with the increasing of the mole ratio ofε-caprolactone to phthaloyl chitosan oligosaccharide. Besides, new crystal domains of polycaprolactone side chains occurred and had melting endothermic peak of PCL in PHCSO-g-PCL while the crystal structure of CSO was damaged.4. The thermoplastic chitosan oligosaccharide-g-polycaprolactone composite (TPHCSO-g-PCL) were successfully synthesized via ring-opening polymerization ofε-caprolactone (ε-CL) using phthaloyl-chitosan as intermediate while the feed ratio ofε-caprolactone to phthaloyl chitosan oligosaccharide precursor (PHCSO) is 15:1 (mL/g). The physical properties of the graft copolymers were characterized by TGA, WAXD, SEM and DSC, respectively. The results showed that the original structure of CSO was changed to some extent by the grafting of PCL to the backbone of CSO. The temperature at 5% weight loss of CSO, pure PCL and PHCSO-g-PCL are 205℃,224℃and 252℃, respectively. TGA analysis showed that TPHCSO-g-PCL was more thermal stable than original CSO. Spherulite morphology of this material can be observed by POM. The melting point of TPHCSO-g-PCL is 60.2℃.5. PHCSO-g-PCL-g-Chol* (n=4,8) was synthesized by coupling the hydroxyl group of PHCSO-g-PCL with the carboxyl of single hexanedioic acid cholesterol ester (M1) or single sebacic cholesterol ester (M2) via acylation reaction. PHCSO-g-PCL-g-Chol* (n=8) has thermoplasticity. The cholesteric liquid crystal texture of M1, M2 and the birefringence phenomeon of PHCSO-g-PCL-g-Chol* (n=8) during the melting process was observed by POM. DSC curve showed that PHCSO-g-PCL-g-Chol* (n=8) has maximum melting endothermic peak at 89℃.