Synthesis Of Lactide From Lactic Acid Oligomers And Modified Poly(D,L-Lactic Acid)

Biodegradable polymers were the important biomaterials, such as polylactide. (D,L-lactide), a monomer of polylactide, was synthesized from oligomer with lactate as the first step of synthesis of Poly(D,L-lactide). Then it was used as raw material to prepare new biodegradable copolymers MAh-modified PDLLA catalysed by Sn(Oct)2-p-toluenesulfonic acid system and PDLLA-(MAh-Diol)_n-PDLLAs initiated by (MAh-Diol)_n prepolymer. The structures and properties of obtained polymers were characterized by the means of fourier transform infrared spectrometer(FTIR), nuclear magnetic resonance spectrometer(NMR), GPC-multi-angle laster light scattering (GPC- MALLS), differential scanning calorimeter(DSC) and other classical chemical analysis. Thereafter, the surface wettability, biodegradation and biocompatibility of (MAh-Diol)_n-modified poly(D,L-lactide) were investigated. The main works and conclusion are summarized as follows:â‘ With oligomer of lactic acid as raw material and lactate as catalyst ,The D,L-lactide was synthesized. Then the effects of raw material and catalyst towards the reaction were extensively investigated, and the reaction conditions were optimized.1) The main component of oligomer of lactic acid were water(13.0%), lactic acid and its oligomer (75.3%), catalyst(8.0%) and carbide(3.7%) by the means of KarlFischer water titration apparatus, atomic absorbption spectrometer and so on.2) The catalyst recycled from oligomer of lactic acid was still lactate with microstructure changed. It catalysed the dehydration and depolymerization in the course of synthesis of D,L-lactide.3) The polycondensation of oligomer was processed dominatedly in course of preparation of D,L-lactide with oligomer of lactic acid as raw material, while polycondensation between lactic acid and between lactic acid and oligomer was processed with lactic acid as raw material, which was caused by difference of raw material and activity of catalyst. Therefore, the content of acid of production was higher with oligomer as raw material.4) The dosage of catalyst was the main facter by orthogonal experiment. The optimum conditions were: weight ratio of lactic acid to oligomer was 2:1, weight ratio of fresh catalyst to raw material was 7:1000, tne time of the second phase of dehydration was 2 h.. â‘¡MAh-modified poly(D,L-lactide) was synthesized by melt ring-opening polymerization of D,L-lactide and maleic anhydride using Sn(Oct)2-p-toluenesulfonic acid as co-initiating system.1) The results of ¹H-NMR analysis indicated that the Sn(Oct)2-p-toluenesulfonic acid system could improve the activity of monomers, therefore, the content of MAh in MAh-PDLLA increased comparing with that in MAh-PDLLA initiated by Sn(Oct)2.2) FTIR, ¹³C-NMR and ¹H-NMR results showed that MAh-PDLLA was successfully prepared initiatated by Sn(Oct)2-p-toluenesulfonic acid system. Glass transition temperature of the synthetic copolymer determined by DSC was 50.9℃.3) The surface wettability evaluation was based on static water contact angle and water absorption ratio. The results indicated that the static water contact angle of copolymer MAh-PDLLA decreased appreciably comparing with that of PDLLA (Mw=2.54×10⁴). While the water absorption ratio was obviously different: PDLLAn-PDLLA with unsaturated bond was synthesized by copolymerizing lactide and prepolymer, which was prepared by the polycondensation of maleic anhydride and diol. The advantage of using (MAh-Diol)_n was due to its hydrophility and biocompatibility. Furthemore, unsaturated bond in the molecular chain could be crosslinked processively.1) The molecular weight of copolymers was lower than that of PDLLA by reason of (MAh-Diol)_n adding. Moreover, decreasing the content of (MAh-Diol)_n in the reacting system yielded copolymer with higher molecular weight and narrower polydispersity.2) The effects of reaction temperature on copolymer molecular weight were investigated under different temperature 145℃,150℃,160℃. The results indicated that increasing the temperature yielded copolymer with lower molecular and wider polydispersity because of outstanding chain-transfer and transesterification.3) The effects of reaction time on copolymer molecular weight were investigated with different time 12h, 24h, 36h, 48h. The results revealed that prolonging the time yielded copolymer with higher molecular weight with time limited in certain range. 4) The effects of content of catalyst on copolymer molecular weight were investigated. The results indicated that decreasing the molar ratio of catalyst to D,L-lactide yielded copolymer with higher molecular weight with molar ratio of catalyst to D,L-lactide limited in 1/7000-1/5000. 5) FTIR, ¹H-NMR and ¹³C-NMR analysis indicated that diol and unsaturated group were successfully set in the molecular chain of PDLLA through copolymerizing of (MAh-Diol)_n and D,L-lactide. DSC analysis reveals glass transition temperature of the synthetic copolymers PDLLA-(MAh-Diol)_n-PDLLA was lower than that of PDLLA. Moreover, viscosimeter analysis indicated the viscosity was reducing with decreasing of copolymer molecular weight.6) The surface wettability evaluation was based on static water contact angle and water absorption ratio. The results indicated that the static water contact angle of copolymers(series of PMEP and PMPEP) was close to that of PDLLA with similar molecular weight. While the water absorption ratio was obviously different: PDLLAn: PMEP-1(30.9%)>PMEP-4(24.6%);PMPEP-120%(37.2%)>PMPEP-215%(31.9%)>PMPEP-410%(26.8%).7) In the whole degrading period of PMPEP materials in distilled water, the rule of the pH value changing was as follows: At first, the pH value of PMPEP-120%,PMPEP-215% was slowly decreasing and then the pH value significantly decreased. While the decreasing rate of the pH value of PMPEP-315% was faster than that of PMPEP-120% and PMPEP-215% at first; then the pH value clearly decreased with slower rate. In conclusion, the degrading rate of PMPEP was faster than PDLLA because of its well-hydrophility.8) The change of weight loss in PBS medium during degradation was investigated. The results revealed that there were two stage in whole degradation period: one was the stage of slowly decreasing of weight; the other was the stage of fleetly decreasing of weight. Furthermore, ¹H-NMR analysis revealed that hydrolyzation happened in the block of PDLLA at first and then at ester-bond between MAh and PEG, PEG and PDLLA, block of PDLLA, respectively.â‘£The biocompatibility of PMPEP materials was estimated by mean of MTT assey. The results indicated that PMPEP could promote hepatocell attachment and growth due to considerable (MAh-PEG)_n chain with well-hydrophility and compatibility of certain protein.⑤Copolymers PMEP-1,PMEP-2,PMEP-3 were crosslinked initiated by BPO with or without crosslinking reagent. The results revealed that the degree of unsaturation and the activity of unsaturated group were the main factors during crosslinking. 1) The molecular weight of crosslinked PMEP-1, PMEP-2, PMEP-3 was in the sequence of LPMEP-11>LPMEP-21>LPMEP-31. While the conversion rate was in the sequence of LPMEP-2> LPMEP-3> LPMEP-1.2) The molecular weight of crosslinked products was evidently increasing with certain content of crosslinking regent.