Study On Synthesis Of Carboxymethyl Starch, C-3 Regioselective Carboxymethylation And Sustained-release

Carboxymethyl starch is a kind of important industrial raw material. This study mainly involves optimization of synthetic technology of CMS, properties analysis, design of C-3 carboxymethylation, interaction with enzymes and carboxymethyl starch-chitosan sustained-release system. Research results are concluded as follows.1 Synthesis of carboxymethyl starch with solvent method:Highe substitution degree carboxy methyl starch (DS=1.06) was prepared through a single step and multi-step reaction with ethanol as solvent, which is a kind of environment friendly, low cost, easily recycled solvent. Plackett-Burman factor experiments, hill-climbing experiments and Response surface experiments were used for screening of significant influence factors, range of factors level and optimum technology respectively. FT-IR and Raman spectrum were used for sample analysis.2 Characterization of carboxymethyl starch:Equipments of CD, scanning electron microscope, X-ray diffraction, thermogravimetric analysis, nuclear magnetic resonance (NMR) and viscometer equipment were used for characteristic analysis, such as:infrared characteristics of CMS, light transmittance, microcosmic structure and microscopic properties, thermal stability, biodegrability.The light transmittance of carboxymethyl starch solution improved significantly (more than 85%). The decomposition temperature of starch decreased after carboxymethylaion. The shape of starch granule became irregular spherical from Smooth ellipsoid. Solution of carboxymethyl potato starch was pseudoplastic at 20-60℃. Carboxymethylation was found in C2, C3, C6 in AGU, however distribution in C2 and C6 were higher than C3 obviously.Along with the increase of DS, the number of chiral carbon atoms increase, and the whole molecules asymmetric is more significant. When pH value changed from neutral to acidic or alkaline, carboxy methyl starch conformational changed obviously, absorption peaks at 185nm blue shift, peak intensity increased, and the whole CD character carboxymethyl starch enhanced. 3 Synthesis and identification of C-3 carboxymethyl starch:First preparatioin of C-3 carboxymethyl starch was completed with dimethylthexysilyl chloride as protective group to protect C-2, C-6 hydroxy and carboxy methyl starch and intermediate product were identified by elemental analysis, NMR and FT-IR methods. The results showed that this method can synthesize C-3 regiolselective carboxymethyl starch successfully.The reaction process experiment shows:dimethylthexysilyl chloride as protection group can occupied the C6, C2 sites of AGU unit ring successfully, and the group remain stable in the next carboxymethylation step. TBAF can remove protection group in C2, C6 sites, and make hydroxyl to re-generate.4 Interaction between Carboxy methyl starch and pepsin, trypsin:the enzyme activity, UV spectra characteristics, fluorescence spectra character of interaction between carboxy methyl starch and two types of protease were analyzied. The results showed that carboxy methyl starch solution can make certain inhibition effect on stomach protein have certain inhibition of pepsin, while no obvious inhibition on trysin. The activity of pepsin decreased when the amount and substitution degree of carboxymethyl starch increased. The enzyme activity became stable after adding carboxymethyl starch for 30min.The fluorescence intentity of pepsin enhances after adding in the Carboxymethyl starch. It can be infered that the area of Trp move from the inside non-polar area to the outside area in accordance with the alteration of the maximum wavelength.5 Preparation and sustained-release of Carboxy methyl starch-chitosan hydrogel system:Carboxymethyl starch-chitosan hydrogel system was prepared firstly, optimize the synthesis process. With hetformin hydrochloride as model drug, sustained-release of the system in vitro was investigated and the internal interaction of system is studied with FT-IR analysis.Compared to commercial products of metformin hydrochloride, release rate of metformin hydrochloride in gel at 30min was 36%, while 80% of commercial product. The System have a fast release rate in the first 2 hours, in which about 50% of the drug released; a slower release step in from 2h to 80h, and completely released step range from 8h to 12h. The release speed of chitosan gel surroundeded by carboxymethyl starch was slower than that without carboxymethyl starch surrounding. This case stated surrounding carboxymethyl starch film could inhabit drug release in a way.There are electrostatic interactions between sodium tripolyph-osphate and chitosan. hydrogen bond interaction between metformin hydrochloride and chitosan was found, interaction between Sodium tripolyph-osphate and chitosan was electrostatic interaction (1598-1566cm-1); The interactions between Carboxy methyl starch and chitosan were hydrogen bond or electrostatic interaction.