聚酯酸酐的合成及其药物释放性能研究

将对羟乙氧基苯甲酸分别与已二酰氯、癸二酰氯和对苯二甲酰氯反应,制备了含酯键的二羧酸.经熔融缩聚,合成了主链含酯键的新型聚酯酸酐.通过¹H NMR、IR及元素分析对单体及聚酯酸酐的结构进行了表征.研究了聚酯酸酐的体外降解和药物释放性能,其降解速率和释药速率次序为:聚4,4'-(已二酰氧二乙氧基)双对苯二甲酸＞聚4,4'-(癸二酰氧二乙氧基)双对苯二甲酸＞聚4,4'-(对苯二甲酰氧二乙氧基)双对苯二甲酸.     

聚酯／聚酸酐共混体系的降解和药物释放行为

聚酯／聚酸酐共混体系的降解和药物释放行为唐爱军，贺晓晖，李福绵（北京大学化学系北京１００８７１）关键词聚癸二酸，聚乳酸，聚己内酯，降解行为，药物释放行为聚酸酐，特别是脂肪类聚酸酥由于其化学价键的水解活泼性，是一类快速生物降解材料．由于聚酸团的水解机制...     

含磷聚酸酐药物控制释放材料的研究

将二氯磷酸乙酯或苯酯与对羟乙氧基苯甲酸反应，制备了含磷酸酯键的二羧酸，将其转化为混合酸酐并通过熔融缩聚，合成了主链含磷酸酯键的聚酯酐，以含磷酸酯键二羧酸与１，３－双（４－羧基苯氧基）丙烷（ＣＰＰ）熔融共聚，得到一链到酯键的共聚酸酐研究了两类聚酸酐的体外降解，酶促降解，这些聚酸酐的降解过程包含酸酐键的断裂，也包含磷酸酯键断裂，前者比后者更容易断裂，核糖核酸酶和碱性磷酸酶能加速这类聚酸酐的降解，还研究     

具有pH-响应性的聚天冬氨酸类载药胶束的制备和释放能力研究

通过大分子引发剂ω-氨基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和水合肼侧基改性,制备了一系列聚乙二醇-聚氨基酸类三嵌段共聚物.其中聚氨基酸链段包括具有酰肼基的聚天冬氨酸衍生物(PAHy),以及疏水性的聚丙氨酸链段.引入具有pH响应性的腙键键合阿霉素,利用键合阿霉素与游离阿霉素之间的π-π叠合作用,在聚合物自组装形成胶束过程中通过化学键合+物理包埋的方式充分负载药物.该胶束以聚丙氨酸链段为核心,以PEG链段为冠层,以PAHy链段为包裹药物的壳层.载药胶束的粒径在170 nm左右.研究不同pH值条件下载药胶束的药物释放能力,随环境pH值的降低药物的释放速率显著增加.     

聚(α,β-L-天冬氨酸丁酯)的合成及水解降解行为研究

以L-天冬氨酸为原料,采用热缩聚法合成聚琥珀酰亚胺.选用醇钠作为亲核试剂,开环反应得到聚(α,β-烷氧基-L-天冬氨酸).该聚合物部分水解制备两亲性聚天冬氨酸(PAsp-Na/PAsp-R).以聚(α,β-L-天冬氨酸丁酯)为例,利用UV、<'1>H NMR等方法研究聚合物的水解降解行为.通过<'1>H NMR中侧链酯基信号的消失和主链游离氨基在紫外光谱中吸光度的变化,证明水解降解过程包括侧链酯键的水解和主链酰胺键的适度裂解两部分,水解过程受环境温度和缓冲溶液pH的共同影响.水解速率具有温度响应性,环境温度越高水解速率越快(37℃时的水解速率>25℃时的水解速率).缓冲溶液pH对聚合物降解速率的影响顺序为:pH 12>pH4>pH 7.     

脂肪族聚酯酸酐的合成及其药物控制释放性能的研究

合成了一系列脂肪族聚酯酸酐并研究了其降解和药物控释性能．结果表明,脂肪族聚酯酸酐具有较低的熔融温度(约70℃);体外降解速率随单体中次甲基数增多而降低,在24～40h降解完全;含乙酰水杨酸的聚酯酸酐基质片的药物释放速率与聚酯酸酐的降解行为有关．     

新型可生物降解医用高分子材料-聚膦腈

聚磷腈是一族由交替的氮、磷原子以交替的单键、双键构成无机主链的新型可生物降解聚合物。聚膦腈具有独特的性质和显著的合成多样性,降解产物为磷酸、氨、氨基酸和乙醇等无毒物质。通过改变聚膦腈侧链结构和组成,可调节聚膦腈的降解速度,控制药物释放的速度。本文主要综述了聚膦腈的合成、降解及其在药物控释系统中的应用。     

聚乙二醇-聚谷氨酸-聚丙氨酸三嵌段共聚物的合成及其胶束的pH-响应性药物控制释放

通过大分子引发剂ω-胺基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和酸性水解制备了一种具有pH-响应性的三嵌段共聚物聚乙二醇-聚谷氨酸-聚丙氨酸(mPEG-PLGA-PLAA).通过核磁共振、ζ-电势、动态光散射、电子显微镜等手段表征了此类三嵌段共聚物的自组装过程及所形成胶束的pH-响应性.使用圆二色谱和红外光谱,分析了胶束结构随环境pH值转变过程中聚氨基酸链段二级结构的变化.以阿霉素作为模型药物,研究了三嵌段共聚物的载药能力和在不同pH条件下的药物释放能力.在碱性条件下,PLGA链段去质子化,链段从疏水性变为亲水性,胶束中间层由于水合作用变得松散,药物释放速率增加;在酸性条件下,PLGA链段质子化,不带电荷,与阿霉素药物分子间的静电相互作用消失.同时,PLGA链段α-螺旋含量增加,形成由链内氢键维持的刚性棒状结构,将链段周围包埋的药物分子"挤出",加速了药物的释放.     

主链含膦酸酯的聚酸酐药物控制释放材料研究

通过二氯膦甲（乙）酸乙酯与对羟乙氧基苯甲酸反应，制备了二羧苯氧乙氧基膦甲（乙）酸乙酯，并其转化成混合醋酐并通过熔融缩聚，合成了主链含膦甲（乙）酸乙酯的聚酸酐，以二羧苯氧乙氧基膦甲（乙）酸乙酯，分别与１，３－双（４－羧基苯氧基）丙烷（ＣＰＰ）及癸二酸（ＳＡ）共聚，得到相应的共聚酸酐，对所合成的单体和聚合物的结构进行了表征，研究了它们的体外降解，酶促降解及其对抗肿瘤药物５－氟尿嘧啶和氨甲喋蛉的释放性能     

乙二醇-聚(咪唑丙基-天冬酰胺)-聚丙氨酸三嵌段共聚物的合成及其pH-响应性药物控制释放性能的研究

聚天冬氨酸及其衍生物是一种具有良好生物相容性和可生物降解性的高分子材料, 被广泛应用于生物医药领域. 本研究通过大分子引发剂ω-胺基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和N-(3-氨丙基)咪唑侧基改性, 制备了一种侧链含有咪唑丙基的聚乙二醇-聚(咪唑丙基-天冬酰胺)-聚丙氨酸三嵌段共聚物. 在水溶液中, 此聚合物可自组装形成一种核-壳-冠型的三层共聚物胶束, 其中疏水性的聚丙氨酸链段自聚集形成胶束的核, 聚(咪唑丙基-天冬酰胺)链段形成具有pH-响应性的壳层, 用于包埋和释放药物, 外围的聚乙二醇链段可以提供一个稳定的水合冠层, 延长药物的体内循环时间. 利用咪唑环与游离阿霉素之间的π-π相互作用和疏水相互作用可以在自组装的过程中将阿霉素包埋到胶束内. 研究发现, 载药胶束随环境pH 值的降低药物的释放速率显著增加. 这主要是由于咪唑环在酸性条件下的质子化导致链段亲疏水性质发生明显变化.     

Synthesis and hydrolytic degradation of poly (glycerol succinate) based polyesters

The limited availability of petroleum resources motivates the research towards value-added products production from bio-resources. This study reports the synthesis of glycerol and succinic acid-based polyesters and their detailed characterization. The modification of poly (glycerol succinate) was done by using other diacids like glutaric acid, adipic acid, azelaic acid, sebacic acid, and dodecanedioic acid. The sysnthesized polyesters were characterized using various techniques such as thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), Nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The addition of different dicarboxylic acids to poly (glycerol succinate) based co-polyesters increased the thermal stability of poly (Glycerol succinate). Glass transition temperatures were obtained in the range of ?17.2 to ?22.5 °C and it increased with chain length. The progress of reaction was monitored by determining acid number, ester number, and degree of esterification. The hydrolytic degradation of polyesters was carried out in acidic and basic medium. The polyesters was found to degrade under basic conditions whereas no weight loss of poly (glycerol succinate) was found under acidic conditions. Particularly, about 40% of poly (glycerol succinate) was degraded within 24 h under basic conditions (pH = 12). The analysis of morphology of polyesters during degradation showed that the increase in hydrolysis time increased the heterogeneity in polyester matrix.     

Synthesis and Characterization of New Functional Poly(ester-anhydride)s Based on Succinic and Sebacic Acids

Summary: New functional poly(ester-anhydride)s with allyl pendant groups in the side chains were obtained by polycondensation of sebacic acid (SBA) and poly(3-allyloxy-1,2-propylene succinate) (OSAGE) terminated with carboxyl groups. The carboxyl groups in OSAGE and in SBA were converted to mixed anhydride groups by acetylation with acetic anhydride. After that, prepolymers obtained were condensed in vacuum to yield higher molecular weight poly(ester-anhydride)s. The influence of SBA and OSAGE content in poly(ester-anhydride)s on their selected properties e.g. molecular weight, thermal and solubility characteristics as well as degradation rate and mode, were examined. Poly(ester-anhydride)s were degraded in aqueous buffer of pH 7.4 at 37 °C. The hydrolytic degradation was monitored by determination of weight loss of samples and by determination of ester to anhydride groups ratio.     

In vitro degradation characteristics of poly(anhydride-imides) containing pyromellitylimidoalanine

The in vitro degradation characteristics of poly(anhydride-imides) containing pyromellitylimidoalanine, with either 1,6-bis(carboxyphenoxy)hexane (CPH) or sebacic acid (SA) were assessed. The copolymers contained up to 50 mol % of the imide monomer, pyromellitylimidoalanine (PMA-ala). Degradation was pH sensitive, being enhanced under basic conditions. Control of degradation times from 2 days to 2 months was achieved by the selection of appropriate monomer units in the polymer backbone. Monomers were chosen based on their solubility in aqueous media, as well as how they influenced the hydrophobicity and crystallinity of the polymer matrices. Polymer degradation was followed by ultraviolet spectroscopy and high-pressure liquid chromatography. Increasing the amount of imide monomer, PMA-ala, and the use of SA (rather than CPH) as the comonomer increased the degradation rate of the polymer matrices. © 1996 John Wiley & Sons, Inc.     

Studies on hydrolytic degradation of poly(ester-anhydride)s based on oligosuccinate and aliphatic diacids

This paper describes synthesis, characteristics and hydrolytic degradation of functional poly(ester-anhydride)s based on oligo(3-allyloxy-1,2-propylene succinate) (OSAGE) and aliphatic diacids (DA). The polymers were obtained by polycondensation of OSAGE with adipic (ADP), sebacic (SBA) or dodecanedicarboxylic acid (DDC). The carboxyl groups in OSAGE and in diacids were converted to mixed anhydride groups by acetylation with acetic anhydride. After that, prepolymers thus obtained were condensed in vacuum to yield poly(ester-anhydride)s. The structure of copolymers was confirmed by NMR spectroscopy. Influence of the kind of diacid and the OSAGE to diacid ratio on selected properties of poly(ester-anhydride)s were examined. Poly(ester-anhydride)s were subjected to hydrolytic degradation at 37 °C, in aqueous phosphate buffer solution of pH 7.41 (PBS). The course of degradation was monitored by determination of weight loss of samples, ¹H NMR and DSC. Fracture surfaces of samples during degradation were examined by scanning electron microscopy.     

Reactions of N-acylated ethyleneimines with thioacetic acid and hydrogen sulfide

A series ofΒ-(S-acetylmercapto)ethylamides ofα-amino acids andα,Β-unsaturated acids and bis[Β-(S-acetylmercapto)ethyl]amides of dicarboxylic acids were obtained by cleavage of N-acylethyleneimines with thioacetic acid. The reaction of ethyleneimides of N-acylamino acids with hydrogen sulfide leads to the correspondingΒ-(N-acylamino)ethylmercaptans. Bis (ethyleneimides) of azelaic and sebacic acids react with hydrogen sulfide to form cyclic sulfides along with the corresponding bis[(Β-mercaptoethyl)amides].     

Reprocessible Epoxy Networks with Tunable Physical Properties: Synthesis,Stress Relaxation and Recyclability

In order to extend the application of epoxy vitrimer,1,4-cyclohexanedicarboxylic acid (CHDA) was used as a co-curing agent and structure modifier for sebacic acid (SA) cured diglycidyl ether of bisphenol A (DGEBA) epoxy vitrimer to tailor the mechanical properties of epoxy vitrimers with 1,5,7-triazabicylo[4.4.0]dec-5-ene (TBD) as a transesterification catalyst.The glass transition temperature (Tg) ofvitrimer increased gradually with the increase in CHDA content.Vitrimers behaved from elastomer to tough and hard plastics were successfully achieved by varying the feed ratio of CHDA to SA.Both the Young's modulus and storage modulus increased apparently with the increase in CHDA content.Stress relaxation measurement indicated that more prominent stress relaxation occurred at elevated temperatures and the stress relaxation decreased with the increase of CHDA content due to the reduced mobility of the vitrimer backbone.The vitrimers showed excellent recyclability as evidenced by the unchanged gel fraction and mechanical properties after compression molded for several times.With tunable mechanical properties,the epoxy vitrimers may find extensive potential applications.     

Preparation, characterization and hydrolytic degradation of poly[p-dioxanone-(butylene succinate)] multiblockcopolymer

A series of poly[p-dioxanone-(butylene succinate)] (PPDOBS) copolymers were prepared from p-dioxanone (PDO), 1,4-butanediol and succinate acids through a two-step process including the initial prepolymer preparation of poly(p-dioxanone)diol (PPDO-OH) and poly(butylene succinate)diol (PBS-OH) and the following copolymerization of the two kinds of prepolymers by coupling with hexamethylene diisocyanate (HDI). The molecular structures of the prepared PPDO-OH, PBS-OH and PPDOBS were characterized by hydrogen nuclear magnetic resonance spectroscopy (¹H NMR). The crystallization of the copolymers was investigated by using differential scanning calorimetry (DSC), polarized optical microscopy (POM) and wide angle X-ray diffraction (WAXD). It has been shown that the crystallization rate and the degree of crystallization increases with the increase of the weight fraction of poly(butylene succinate) (PBS) blocks in the copolymers. In phosphate buffer solution with pH 7.4 at 37 °C for 18 weeks, the hydrolytic degradation behaviors of the copolymers were studied. The changes of retention weight, water absorption, pH value, and surface morphologies with the degradation time showed that the hydrolytic degradation rate of PPDOBS could be controlled by adjusting the weight fraction of poly(p-dioxanone) (PPDO) and PBS blocks in the copolymers. The changes of the thermal properties of PPDOBS during the degradation were also investigated by DSC.     

Metabolic flux analysis of clostridium thermosuccinogenes

Clostridium thermosuccinogenes are anaerobic thermophilic bacteria that ferment various carbohydrates to succinate and acetate as major products and formate, lactate, and ethanol as minor products. Metabolic carbon flux analysis was used to evaluate the effect of pH and redox potential on the batch fermentation of C. thermosuccinogenes. In a first study, the effects of four pH values (6.50, 6.75, 7.00, and 7.25) on intracellular carbon flux at a constant redox potential of -275 mV were compared. The flux of carbon toward succinate and formate increased whereas the flux to lactate decreased significantly with a pH increase from 6.50 to 7.25. Both specific growth rate and specific rate of glucose consumption were unaffected by changes in pH. The fraction of carbon flux at the phosphoenolpyruvate (PEP) node flowing to oxaloacetate increased with an increase in pH. At the pyruvate node, the fraction of flux to formate increased with increasing pH. At the acetyl CoA node, the fraction of flux to acetate increased significantly with an increase in pH. A second study elucidated the effect of four controlled culture redox potentials (-225, -250, -275, and -310 mV) on metabolic carbon flux at a constant pH of 7.25. Lower values of culture redox potential were correlated with increased succinate, acetate, and formate fluxes and decreased ethanol and hydrogen fluxes in C. thermosuccinogenes. Lactate formation was not significantly influenced by redox potential. At the PEP node, the fraction of carbon to oxaloacetate increased with a decrease in redox potential. At the pyruvate node, the fraction of carbon to formate increased, while at the acetyl CoA node, the fraction of carbon flux to acetate increased with reduced redox potential. The presence of hydrogen in the headspace or the addition of nicotinic acid to the growth media resulted in increased hydrogen and ethanol fluxes and decreased succinate, acetate, formate, and lactate fluxes.     

Poly(ester anhydride)s prepared by the insertion of ricinoleic acid into poly(sebacic acid)

New degradable poly(ester anhydride)s were prepared by the melt polycondensation of diacid oligomers of poly(sebacic acid) (PSA) transesterified with ricinoleic acid. The transesterification of PSA with ricinoleic acid to form oligomers was conducted via a melt bulk reaction between a high molecular weight PSA and ricinoleic acid. A systematic study on the synthesis, characterization, degradation in vitro, drug release, and stability of these polymers was performed. Polymers with weight‐average molecular weights of 2000–60,000 and melting temperatures of 24–77 °C were obtained for PSA containing 20–90% (w/w) ricinoleic acid. NMR and IR analyses indicated the formation of ester bonds along the polyanhydride backbone. These new degradable copolymers have potential use as drug carriers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1059–1069, 2003     

Advances in properties and biodegradability of co-continuous,immicisible, biodegradable,polymer blends

A series of blends consisting of polylactic acid (PLA) and aliphatic succinate polyester (Bionolle#3000) have been prepared. The results of the mechanical property investigation have shown that using more than 20 wt % Bionolle#3000 can significantly increase the toughness of the PLA, increase the elongation at break (more than 200%) and increase the impact strength (more than 70 J/m). These properties were not significantly affected by the aging behavior of PLA for more than two months. DMA results show that Bio#3000 reduces the elastic modulus of the blends between −15°C and 60°C. Soil degradation rates of the PLA/Bio#3000 blends also increase with increasing Bio#3000 content. However, for the blends with less than 30 wt % of Bio#3000, the degradation rates do not significantly increase. Enzymatic degradation rates of the blends are higher than for those of the two polymers, and these rates increase with increasing PLA content. Composting biodegradation rates increase with increasing Bio#3000 content.