Ring-opening polymerization of L-lactide and preparation of its microsphere in supercritical fluids

The ring-opening polymerization of L-lactide initiated by stannous octoate was carried out in supercritical chlorodifluoromethane (scR22) at various reaction conditions (time and temperature) and reactant concentrations (initiator, monomer, and solvent). The monomer conversion increased to ca. 70% on increasing the reaction time to 1 h. The molecular weight of the poly(L-lactide) (PLLA) product also increased to ca. 160,000 g x mol(-1) over the same period. Increasing reaction temperature from 90 to 130 degrees C resulted in increased monomer conversion and PLLA molecular weight. A series of polymerizations conducted at various 1-dodecanol and stannous octoate concentrations suggested that stannous octoate does not act as an initiator by itself, and that the tin-alkoxide formed from 1-dodecanol and stannous octoate serves as the initiating species in scR22. While enhancements of the monomer conversion and PLLA molecular weight were observed with increasing monomer concentration, the chlorodifluoromethane concentration had the opposite on both. After the polymerization, PLLA microspheres were prepared in situ by using a continuous supercritical antisolvent process without residual organic solvent and monomer to yield highly purified microspheres for environmental and biomedical applications.     

开环聚合-固相缩聚法制备立体嵌段聚乳酸

首先,采用乳酸为引发剂,辛酸亚锡为催化剂,引发丙交酯开环聚合制得具有缩聚活性的L-聚乳酸和D-聚乳酸;然后,将两者熔融共混后进行固相缩聚,合成了一系列立体嵌段聚乳酸。采用核磁共振(NMR)、凝胶渗透色谱(GPC)及差示扫描量热仪(DSC)分析了产物的链结构、重均分子量、热性能,并探讨了均相晶体和立体复合晶体共存情况下的固相缩聚机理。结果表明,固相缩聚产物分子量增长的适宜反应条件为:反应时间30h,较低的催化剂含量,L-聚乳酸质量分数为80%。L-聚乳酸和D-聚乳酸共混物较低的初始立体复合晶体结晶度有利于后续固相缩聚过程中产物分子量的增长;固相缩聚不仅发生在异链之间,而且也发生在同链之间。     

Oligoethylene‐end‐capped polylactides

Oligoethylene‐end‐capped polylactides were synthesized through the ring‐opening polymerization of L ‐lactide with alcohol‐terminated oligoethylenes as macroinitiators. The polymerization of L ‐lactide was carried out in bulk at 130 °C in the presence of stannous octoate and primary alcohols with four different molecular weights: 350, 425, 550, and 700 g/mol. The end‐capped copolymers that formed had a number‐average molecular weight of approximately 40,000 (weight‐average molecular weight/number‐average molecular weight = 1.7) according to gel permeation chromatography and were highly crystalline in comparison with the similarly formed homopolymer of L ‐lactide. The copolymer structure was characterized by Fourier transform infrared, NMR, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry, and differential scanning calorimetry analysis. This work focused on developing more crystallizable and hydrolytically stable polylactide derivatives that could potentially be used as compatibilizers in polylactide–polyolefin blends or as nucleating agents for poly(L ‐lactide) or other polyesters. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5257–5266, 2005     

Synthesis and characterization of multiblock copolymers composed of poly(5‐methyl‐5‐benzyloxycarbonyl‐1,3‐dioxan‐2‐one) outer blocks and poly(L‐lactide) inner blocks

Ethylene glycol (EG) initiated, hydroxyl‐telechelic poly(L ‐lactide) (PLLA) was employed as a macroinitiator in the presence of a stannous octoate catalyst in the ring‐opening polymerization of 5‐methyl‐5‐benzyloxycarbonyl‐1,3‐dioxan‐2‐one (MBC) with the goal of creating A–B–A‐type block copolymers having polycarbonate outer blocks and a polyester center block. Because of transesterification reactions involving the PLLA block, multiblock copolymers of the A–(B–A)_n–B–A type were actually obtained, where A is poly(5‐methyl‐5‐benzyloxycarbonyl‐1,3‐dioxan‐2‐one), B is PLLA, and n is greater than 0. ¹H and ¹³C NMR spectroscopy of the product copolymers yielded evidence of the multiblock structure and provided the lactide sequence length. For a PLLA macroinitiator with a number‐average molecular weight of 2500 g/mol, the product block copolymer had an n value of 0.8 and an average lactide sequence length (consecutive C₆H₈O₄ units uninterrupted by either an EG or MBC unit) of 6.1. For a PLLA macroinitiator with a number‐average molecular weight of 14,400 g/mol, n was 18, and the average lactide sequence length was 5.0. Additional evidence of the block copolymer architecture was revealed through the retention of PLLA crystallinity as measured by differential scanning calorimetry and wide‐angle X‐ray diffraction. Multiblock copolymers with PLLA crystallinity could be achieved only with isolated PLLA macroinitiators; sequential addition of MBC to high‐conversion L ‐lactide polymerizations resulted in excessive randomization, presumably because of residual L ‐lactide monomer. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6817–6835, 2006     

溶液法星型聚乳酸的合成与表征

探讨了采用辛酸亚锡为催化剂,多元醇及多元酸为引发剂,以溶液法制备星型聚乳酸的可行性,研究了不同引发剂对产物分子量的影响.采用核磁共振及DSC对产物进行了表征,结果表明:以溶液法合成星型聚乳酸是可行的,但与丙交酯开环聚合制备星型聚乳酸的方法相比,溶液法在产物结构和分子量控制上并不十分有效,由于反应受到多官能团核引发剂空间位阻和反应概率的影响,聚乳酸产物的结构除星型结构外也同时存在大量的线型结构.     

More about the polymerization of lactides in the presence of stannous octoate

The ring-opening polymerization of lactide cyclic monomers in the bulk in the presence of tin(II) 2-ethylhexanoate (stannous octoate or SnOct₂) was reexamined under conditions allowing for the end group characterization of growing chains by high-resolution ¹H-NMR. Data collected for low values of the monomer/initiator (M/I) ratio showed that the DL -lactide ring was opened to yield lactyl octoate-terminated short chains. A cationic-type mechanism involving co-initiation by octanoic acid was proposed to account for experimental findings. The formation of a side product, hydroxytin(II) lactate (HTL), was found which appeared able to initiate lactide polymerization and to yield a high molecular weight PLA50 polymer. However the polymerization with stannous octoate was faster than the HTL one. Anyhow, data suggested that both SnOct₂ and HTL are likely to act simultaneously as initiators during the polymerization of lactides in the presence of SnOct₂. A complete reaction scheme was proposed to account for the presence of the various compounds likely to be formed under these conditions. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 3431–3440, 1997     

Biodegradable Polymers for Orthopedic Applications: Synthesis and Processability of Poly (l-Lactide) and Poly (Lactide-co-€-Caprolactone)

Abstract

The synthesis of poly(l-lactide) (PLLA), poly(l-lactide-co-e-caprolactone), and poly(DL-lactide-co-e-caprolactone) by ring-opening bulk polymerization was investigated. Polymerization temperature had a significant effect on the PLLA molecular weight. At 184°C a polymer with a molecular weight of only 10 × 10⁴ resulted. This was lower by a factor of 2 than that obtained at 103 and 145°C. The stannous octoate (SnOct) concentration, with a monomer/SnOct molar ratio in the range of 1,000 to 10,000, was not found to have a significant effect on the PLLA molecular weight. A heterogeneous structure in polymerized PLLA was observed. The intrinsic viscosity of poly(lactide-co-€-caprolactone), obtained at 130°C, monomer/SnOct molar ratio 5,000, and polymerization time of 30 hours, decreased with increasing €-caprolactone content within the first 9 wt% and then leveled off. Die-drawing of PLLA cylinders, for the purpose of increasing the polymer's mechanical strength, was unsuccessful due to the brittleness of the polymer. The drawability of poly(l-lactide), however, was greatly improved by copolymerization with €-caprolactone. With only 3 wt% of €-caprolactone, for example, the tensile strength of die-drawn poly(l-lactide-co-e-caprolactone) was increased by a factor of more than 3. Polymer processing temperature was also investigated. The requirement for low processing temperatures in melt manufacture of controlled release matrix devices containing thermal sensitive drugs was accomplished by three methods: through the use of low molecular weight poly(DL-lactide), adding (DL-lactic) acid oligomer to high molecular weight PDLLA, and copolymerizing DLLA with €-caprolactone. The glass transition temperatures of the modified high molecular weight PDLLA decreased significantly. Melt extrusion below 100°C could be performed.     

Synthesis of star‐shaped poly(D,L‐lactic acid‐alt‐glycolic acid)‐b‐poly(L‐lactic acid) with the poly(D,L‐lactic acid‐alt‐glycolic acid) macroinitiator and stannous octoate catalyst

Two types of three‐arm and four‐arm, star‐shaped poly(D,L ‐lactic acid‐alt‐glycolic acid)‐b‐poly(L ‐lactic acid) (D,L ‐PLGA50‐b‐PLLA) were successfully synthesized via the sequential ring‐opening polymerization of D,L ‐3‐methylglycolide (MG) and L ‐lactide (L ‐LA) with a multifunctional initiator, such as trimethylolpropane and pentaerythritol, and stannous octoate (SnOct₂) as a catalyst. Star‐shaped, hydroxy‐terminated poly(D,L ‐lactic acid‐alt‐glycolic acid) (D,L ‐PLGA50) obtained from the polymerization of MG was used as a macroinitiator to initiate the block polymerization of L ‐LA with the SnOct₂ catalyst in bulk at 130 °C. For the polymerization of L ‐LA with the three‐arm, star‐shaped D,L ‐PLGA50 macroinitiator (number‐average molecular weight = 6800) and the SnOct₂ catalyst, the molecular weight of the resulting D,L ‐PLGA50‐b‐PLLA polymer linearly increased from 12,600 to 27,400 with the increasing molar ratio (1:1 to 3:1) of L ‐LA to MG, and the molecular weight distribution was rather narrow (weight‐average molecular weight/number‐average molecular weight = 1.09–1.15). The ¹H NMR spectrum of the D,L ‐PLGA50‐b‐PLLA block copolymer showed that the molecular weight and unit composition of the block copolymer were controlled by the molar ratio of L ‐LA to the macroinitiator. The ¹³C NMR spectrum of the block copolymer clearly showed its diblock structures, that is, D,L ‐PLGA50 as the first block and poly(L ‐lactic acid) as the second block. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 409–415, 2002     

Synthesis of four‐arm star poly(L‐lactide) oligomers using an in situ‐generated calcium‐based initiator

Using an in situ‐generated calcium‐based initiating species derived from pentaerythritol, the bulk synthesis of well‐defined four‐arm star poly(L ‐lactide) oligomers has been studied in detail. The substitution of the traditional initiator, stannous octoate with calcium hydride allowed the synthesis of oligomers that had both low PDIs and a comparable number of polymeric arms (3.7–3.9) to oligomers of similar molecular weight. Investigations into the degree of control observed during the course of the polymerization found that the insolubility of pentaerythritol in molten L ‐lactide resulted in an uncontrolled polymerization only when the feed mole ratio of L ‐lactide to pentaerythritol was 13. At feed ratios of 40 and greater, a pseudoliving polymerization was observed. As part of this study, in situ FT‐Raman spectroscopy was demonstrated to be a suitable method to monitor the kinetics of the ring‐opening polymerization of lactide. The advantages of using this technique rather than FTIR‐ATR and ¹H NMR for monitoring L ‐lactide consumption during polymerization are discussed. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4736–4748, 2009     

Emulsion copolymerization of D,L‐lactide and glycolide in supercritical carbon dioxide

Biodegradable polyesters were synthesized via an emulsion polymerization in supercritical carbon dioxide (SC‐CO₂). Copolymers of lactide and glycolide were synthesized in SC‐CO₂ with stannous octoate as the ring‐opening catalyst and a fluorocarbon polymer surfactant as an emulsifying agent. The conversion of lactide and glycolide was monitored with respect to the reaction time and temperature with ¹H NMR spectroscopy. The conversion of glycolide surpassed 99% within 72 h for an SC‐CO₂ phase maintained at 200 bar and 70 °C. Under the same conditions, lactide conversion reached 65% after 72 h of polymerization. Unpolymerized monomer was removed after the reaction by extraction with an SC‐CO₂ mobile phase. The molecular weights of all the copolymers were measured by gel permeation chromatography. Weight‐average molecular weights (M_w) ranged between 2500 and 30,200 g/mol and polydispersity indices ranged from 1.4 to 2.3 for polymerization times of 6 and 48 h, respectively. Although the molecular weight increased significantly during the first 48 h of reaction, there was no significant difference in the M_w for polymerization times of 48 and 72 h. Emulsion polymerization within the benign solvent SC‐CO₂ demonstrated improved conversion and molecular weight versus polymers synthesized without surfactant. The emulsion polymerization of lactide and glycolide copolymers in SC‐CO₂ is proposed as a novel production technique for high‐purity, biodegradable polymers. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 562–570, 2001     

Ring-opening precipitation polymerization of poly(D,L-lactide-co-glycolide) in supercritical carbon dioxide

The biodegradable polymer poly(D ,L -lactide-co-glycolide) was synthesized by a ring-opening precipitation polymerization in supercritical CO₂ using stannous octoate as initiator. Following polymerization, unreacted monomer was removed by supercritical fluid extraction and the polymer was recovered as a porous solid upon depressurization of the CO₂ phase. The lactide to glycolide ratio of the polymer was determined to be 70.7 : 29.3 using ¹³C NMR spectroscopy. The weight-average molecular weight of the product was measured to be 3 500, with a polydispersity of 1.4 using gel permeation chromatography.     

Synthesis and characterization of poly(L‐lactide‐co‐ε‐caprolactone) (B)‐poly(L‐lactide) (A) ABA block copolymers

ABA triblock copolymers of L ‐lactide (LL) and ε‐caprolactone (CL), designated as PLL‐P(LL‐co‐CL)‐PLL, were synthesized via a two‐step ring‐opening polymerization in bulk using diethylene glycol and stannous octoate as the initiating system. In the first‐step reaction, an approximately 50:50 mol% P(LL‐co‐CL) random copolymer (prepolymer) was prepared as the middle (B) block. This was then chain extended in the second‐step reaction by terminal block polymerization with more L ‐lactide. The percentage yields of the triblock copolymers were in excess of 95%. The prepolymers and triblock copolymers were characterized using a combination of dilute‐solution viscometry, gel permeation chromatography (GPC), ¹H‐ and ¹³C‐NMR, and differential scanning calorimetry (DSC). It was found that the molecular weight of the prepolymer was controlled primarily by the diethylene glycol concentration. All of the triblock copolymers had molecular weights higher than their respective prepolymers. ¹³C‐NMR analysis confirmed that the prepolymers contained at least some random character and that the triblock copolymers consisted of additional terminal PLL end (A) blocks. From their DSC curves, the triblock copolymers were seen to be semi‐crystalline in morphology. Their glass transition, solid‐state crystallization, and melting temperature ranges, together with their heats of melting, all increased as the PLL end (A) block length increased. Copyright © 2005 John Wiley & Sons, Ltd.     

以季戊四醇为引发剂的星形聚对二氧环己酮的合成

本文以辛酸亚锡(SnOct2)为催化剂,以季戊四醇(PTOL)为引发剂,引发对二氧环己酮PDO单体开环聚合,合成了具有新颖结构的星形PPDO,研究了单体和引发剂的比例、单体和催化剂的比例、温度、时间等反应条件对聚合反应的影响,结果表明,通过调节PDO和PTOL的比例可以控制聚合产物的分子量。     

聚乳酸接枝葡聚糖共聚物的合成及其体外降解行为的研究

研究了聚乳酸接枝葡聚糖梳型共聚物的合成 ,以及共聚物的结构特征、亲水性能及降解行为的表征 .结果表明由于亲水性葡萄糖单元组分的引入以及共聚物的梳型结构特征 ,聚乳酸接枝葡聚糖共聚物的亲水性明显优于相应的线型聚乳酸 ,而且降解速度也明显加快 .由于这类梳型结构的聚多糖 聚酯共聚物综合了聚多糖细胞亲和性好和聚酯生物降解速率可调节性的特点 ,因此有望成为一类优良的细胞支架材料 .     

Preparation of methoxy poly(ethylene glycol)/polyester diblock copolymers and examination of the gel‐to‐sol transition

Diblock copolymers consisting of methoxy poly(ethylene glycol) (MPEG) and poly(?‐caprolactone) (PCL), poly(δ‐valerolactone) (PVL), poly(L ‐lactic acid) (PLLA), or poly(lactic‐co‐glycolic acid) (PLGA) as biodegradable polyesters were prepared to examine the phase transition of diblock copolymer solutions. MPEG–PCL and MPEG–PVL diblock copolymers and MPEG–PLLA and MPEG–PLGA diblock copolymers were synthesized by the ring‐opening polymerization of ?‐caprolactone or δ‐valerolactone in the presence of HCl · Et₂O as a monomer activator at room temperature and by the ring‐opening polymerization of L ‐lactide or a mixture of L ‐lactide and glycolide in the presence of stannous octoate at 130 °C, respectively. The synthesized diblock copolymers were characterized with ¹H NMR, IR, and gel permeation chromatography. The phase transitions for diblock copolymer aqueous solutions of various concentrations were explored according to the temperature variation. The diblock copolymer solutions exhibited the phase transition from gel to sol with increasing temperature. As the polyester block length of the diblock copolymers increased, the gel‐to‐sol transition moved to a lower concentration region. The gel‐to‐sol transition showed a dependence on the length of the polyester block segment. According to X‐ray diffraction and differential scanning calorimetry thermal studies, the gel‐to‐sol transition of the diblock copolymer solutions depended on their degrees of crystallinity because water could easily diffuse into amorphous polymers in comparison with polymers with a crystalline structure. The crystallinity markedly depended on both the distinct character and composition of the block segment. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5784–5793, 2004     

Synthesis and properties of multiblock copolymers consisting of poly(L‐lactic acid) and poly(oxypropylene‐ co‐oxyethylene) prepared by direct polycondensation

A multiblock copoly(ester–ether) consisting of poly(l ‐lactic acid) (PLLA) and poly(oxypropylene‐co‐oxyethylene) (PN) was prepared and characterized. Preparation was done via the solution polycondensation of a thermal oligocondensate of l ‐lactic acid, a commercially available telechelic polyether (PN: Pluronic‐F68), and dodecanedioic acid as a carboxyl/hydroxyl adjusting agent. When stannous oxide was used as the catalyst, the molecular weight of the resultant PLLA/PN block copolymers became very high (even with a high PN content) under optimized reaction conditions. The refluxing of diphenyl ether (solvent) at reduced pressure allowed the efficient removal of the condensed water from the reaction system and the feed‐back of the intermediately formed l ‐lactide at the same time in order to successfully bring about a high degree of condensation. The copolymer films obtained by solution casting became more flexible with the increasing PN content as soft segments. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1513–1521, 1999     

Molecular Weight Control in Emulsion Polymerization by Catalytic Chain Transfer: A Reaction Engineering Approach

Summary: For the application of catalytic chain transfer in (mini)emulsion polymerization, catalyst partitioning and deactivation are key parameters that govern the actual catalyst concentration at the locus of polymerization and consequently the final molecular weight distribution. A global model, based on the Mayo equation, catalyst partitioning and deactivation was developed. The influence of several reaction parameters on the instantaneous number average molecular weight was quantified.     

Melt block copolymerization of ϵ-caprolactone and L-lactide

AB block copolymers of ϵ-caprolactone and (L )-lactide could be prepared by ring-opening polymerization in the melt at 110°C using stannous octoate as a catalyst and ethanol as an initiator provided ϵ-caprolactone was polymerized first. Ethanol initiated the polymerization of ϵ-caprolactone producing a polymer with ϵ-caprolactone derived hydroxyl end groups which after addition of L -lactide in the second step of the polymerization initiated the ring-opening copolymerization of L -lactide. The number-average molecular weights of the poly(ϵ-caprolactone) blocks varied from 1.5 to 5.2 × 10³, while those of the poly(L -lactide) blocks ranged from 17.4 to 49.7 × 10³. The polydispersities of the block copolymers varied from 1.16 to 1.27. The number-average molecular weights of the polymers were controlled by the monomer/hydroxyl group ratio, and were independent on the monomer/stannous octoate ratio within the range of experimental conditions studied. When L -lactide was polymerized first, followed by copolymerization of ϵ-caprolactone, random copolymers were obtained. The formation of random copolymers was attributed to the occurrence of transesterification reactions. These side reactions were caused by the ϵ-caprolactone derived hydroxyl end groups generated during the copolymerization of ϵ-caprolactone with pre-polymers of L -lactide. The polymerization proceeds through an ester alcoholysis reaction mechanism, in which the stannous octoate activated ester groups of the monomers react with hydroxyl groups. © 1997 John Wiley & Sons, Inc.     

Novel poly(l‐lactide)/poly(d‐lactide)/poly(tetrahydrofuran) multiblock copolymers with a controlled architecture: Synthesis and characterization

Novel poly(l ‐lactide) (PLLA)/poly(d ‐lactide) (PDLA)/poly(tetrahydrofuran) (PTHF) multiblock copolymers with designed molecular structure were synthesized by a two‐stage procedure. Well‐defined PDLA‐PLLA‐PTHF‐PLLA‐PDLA pentablock copolymers were prepared by sequential ring opening polymerization of l ‐ and d ‐lactides starting from PTHF glycol, with the length of the (equimolar) PLLA and PDLA blocks being varied. Then, these dihydroxyl‐terminated pentamers were transformed into multiblock copolymers by melt chain‐extension with hexamethylene diisocyanate–being the first time that the coupling of pentablock units is reported. The successful formation of macromolecular chains with a multiblock and well‐defined architecture was demonstrated by ¹H NMR spectroscopy. The thermal properties and structuring of the resulting materials were investigated by means of DSC and WAXD measurements and DMA analysis. Stereocomplexation was found to be promoted during solution and melt crystallization. This approach affords materials combining the high rigidity and strength (other than improved thermal resistance) of the hard stereocomplex crystallites with the flexibility imparted by the soft block, whereby their properties can be finely tailored through the composition of the basic pentablock units without limitations on the final molecular weight. The adopted reaction conditions make this process highly appealing in view of the possibility to perform it in extruder. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3269–3282     

Synthesis and properties of high‐molecular‐weight stereo di‐block polylactides with nonequivalent D/L ratios

Di‐stereoblock polylactides (di‐sb‐PLA: PLLA‐b‐PDLA) having high molecular weight (M_n > 100 kDa) were successfully synthesized by two‐step ring‐opening polymerization (ROP) of L ‐ and D ‐lactides using tin(2‐ethylhexanoate) as a catalyst. By optimizing the polymerization conditions, the block sequences were well regulated at non‐equivalent feed ratios of PLLA and PDLA. This synthetic method consisted of three stages: (1) polymerization of either L ‐ or D ‐lactide to obtain a PLLA or PDLA prepolymer with a molecular weight less than 50 kDa, (2) purification of the obtained prepolymer to remove residual lactide, and (3) polymerization of the enantiomeric lactide in the presence of the purified prepolymer. Their ¹³C and ³¹P NMR spectra of the resultant di‐sb‐PLAs strongly supported their di‐stereo block structure. These di‐sb‐PLAs, having weight‐average molecular weights higher than 150 kDa, were fabricated into polymer films by solution casting and showed exclusive stereocomplexation. The thermomechanical analysis of the films revealed that their heat deformation temperature was limited probably because of their low crystallinity owing to the non‐equivalent PLLA/PDLA ratio. The blend systems of the di‐sb‐PLAs having complementary stereo‐sequences (the one with a long PLLA block and the other with long PDLA block) were also prepared and characterized to enhance the sc crystallinity. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 794–801, 2010