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     

主链含己烷雌酚的聚酸酐的合成及其降解性能研究

聚酸酐是一类新型的药物控制释放载体材料,具有良好的生物相容性和表面溶蚀性能^[1].聚酸酐的降解和药物释放速率可通过改变单体结构、共聚物的组成和主链上的酸酐键密度实现.后者主要是把降解速率不同的酯键、酰(亚)胺键和磷酸酯键引入主链上.     

聚膦腈/聚酸酐共混物的相容性和水解行为

采用溶液混合法制备了聚 [(双 甘氨酸乙酯 )膦腈 ](PGP)与聚酸酐 (PSA或PSTP)的共聚物 .利用示差扫描量热仪和相差显微镜研究了两体系的共混相容性 ,发现PGP与PSTP具有部分相容性 .体外降解试验表明 ,PGP PSTP降解行为呈均一性 ,且由于PSTP酸性产物的催化作用 ,降解速度明显较PGP加快 (约 15天 )并随PSTP含量增加而加快 .PGP PSTP有望成为一种新型的药物控释载体材料     

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.     

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     

可降解光交联聚酸酐与聚酰胺-甲基丙烯酰胺凝胶的合成及药物控释

合成聚酰胺-胺型树状分子（PAMAM）并进行端基甲基丙烯酰基修饰,将最外层接枝光化学活性双键,修饰产物与甲基丙烯酸酐化癸二酸(MSA)用DMSO溶解并在光引发剂存在下,经过紫外光照射得到具有一定生物相容性的凝胶。运用1H NMR和FT-IR对聚酰胺-甲基丙烯酰胺的结构进行表征。凝胶的降解实验表明,聚酸酐含量为50-60wt%的凝胶以表面溶蚀的方式降解,随着甲基丙烯酸酐化癸二酸（MSA）在凝胶中含量不同,降解时间在45~60天之间,pH在6.5-8.06范围内改变。包埋氧氟沙星凝胶的降解实验表明,可以通过改变聚酸酐的含量控制降解时间和药物释放量。     

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．     

聚己内酯聚醚嵌段共聚物和共混物的表面性质对其药物释放行为的影响

聚己内酯聚醚嵌段共聚物和共混物的表面性质对其药物释放行为的影响王卫华，贝建中，王智峰，王身国（中国科学院化学研究所北京１０００８０）关键词聚己内酯聚醚嵌段共聚物，共混物，电子能谱，表面性质，药物释放行为聚己内醋（ＰＣＬ）具有优良的药物通透性和生物相容...     

聚磷酸酯—聚氨酯药物释放材料的合成

报道了一类新型生物可降解和生物相容性药物释放材料聚磷酸酯－聚氨酯的合成和表征，研究了这类聚合物的体外降解及其对牛血清白蛋白的释放性能。     

新型聚磷酸酯药物控释材料的合成

采用溶液缩聚方法，制得含酪氨酸烷基酯的聚磷酸酯，再通过大分子反应分别得到主链带正、负电荷的聚磷酸酯，研究了这三类聚磷酸酯的体外降解行为，并对它们作为蛋白质的控制释放材料的性能进行了初步评价。     

Fatty acid terminated polyanhydrides

A systematic study on the synthesis, characterization, degradation, and drug release of fatty acid terminated poly(sebacic acid) (PSA) is reported. Fatty acid terminated sebacic acid polymers were synthesized by melt condensation of acetate anhydrides of linear fatty acids (C8–C18) and sebacic anhydride oligomers to yield waxy off-white materials. Polymers with molecular weights (M_w) in the range of 9,000 and 5,000 were obtained for the 10% and 30% (weight ratio) containing fatty terminals, respectively. Up to about 30% of fatty acid terminals, the final product is mainly fatty terminated polymer with up to about 5% w/w of the symmetric fatty anhydride. Increasing amounts of fatty acid acetate anhydride in the polymerization mixture had little effect on the polymer molecular weight up to a ratio of 40 : 60 (fatty acid acetate : sebacic acid oligomer) which remains in the range of 5,000–8,000. Above this ratio the molecular weight dropped to a level of 2,000–3,000 and the percent of the symmetric anhydride increased to 10–40%. The fatty terminals had little effect on PSA melting point and crystallinity. However, the fatty terminals had a significant effect on the polymer degradation and drug release rate. PSA with 30% w/w of C14–C18 terminals degraded and released the incorporated drug for more than 4 weeks as compared with 10 days for the acetate-terminated PSA. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3337–3344, 1999     

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     

Degradable polymer blends. I. Screening of miscible polymers

Blends of biodegradable polymers having properties distinct from the individual polymer components, and that are suitable for use as carriers of pharmaceutically active agents, were prepared from two or more polyanhydrides, polyesters, and mixtures of polyanhydrides and low molecular weight polyesters. The blends have different properties than the original polymers, providing a mean for altering the characteristics of the polymeric matrix without altering the chemical structure of the component polymers. Aliphatic, aromatic, and copolymers of polyanhydrides were miscible in each other and formed less crystalline compositions with a single melting point which was lower than the melting point of the starting polymers. The polyesters: poly(lactide-glycolide), poly(caprolactone), and poly(hydroxybutyric acid) presented some miscibility in each other. However, the polyanhydrides were immiscible with the polyesters resulting in a complete phase separation both in solution or in melt mixing. Only low molecular weight polyesters (in the range of 2000) of lactide and glycolide, mandelic acid, propylenefumarate, and caprolactone presented some miscibility with polyanhydrides. Similarly, poly(orthoester) and hydroxybutyric acid polymers formed a uniform mixture with the anhydride polymers which had the two melting points of the original polymers. Drug release from polymer blends composed of poly(hydroxybutyric acid) or low molecular weight poly(lactic acid) with poly(sebacic anhydride) (PSA) showed a constant release of drug for periods from 2 weeks to several months as a function of the PSA content in the blend. Increasing the content of PSA, a fast degrading polymer, increases the release rate from the blend. © 1993 John Wiley & Sons, Inc.     

Preparation and characterization of temperature and pH-sensitive chitosan material and its controlled release on coenzyme A

A novel copolymer P(CS–Ma–DMAEMA) was synthesized with chitosan (CS), maleic anhydride (Ma) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) by grafting and copolymerization. The copolymer obtained was analyzed by FT-IR, ¹H NMR and UV, and the molecular weight and polydispersity were determined by gel permeation chromatography (GPC). The average size and distribution of copolymer micelles were determined by dynamic light scattering (DLS). Their aqueous solution properties and controlled coenzyme A delivery were also studied. It was found that the copolymer had temperature sensitivity and pH sensitivity. The factors affecting release behavior, such as concentration, pH and temperature were discussed in this paper. The higher concentration of the copolymer aqueous solution absorbed more coenzyme A than the lower one. The increasing temperature accelerated the drug release from the copolymer. The pH of the copolymer solution had significant impact on the release of coenzyme A. The results suggested that the novel copolymer could be used as drug delivery carrier.     

Tuning salicylate‐based polymers to overcome lag time and extend release via copolymers and polymer blends

This work describes how physicochemical properties of salicylate‐based poly(anhydride‐esters) (PAEs) can be tuned for drug delivery and optimized by comparing copolymerization with polymer blending. These alterations reduced the lag time of drug release, while still maintaining a long‐term drug release profile. The chemical composition of the copolymers and polymer blends was determined by proton nuclear magnetic resonance and additional properties such as molecular weight, glass transition temperature and contact angle measurements were obtained. In vitro salicylic acid release from the copolymers and blends is studied in an environment mimicking physiological conditions. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 685–689     

Synthesis and micellization of amphiphilic poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride) block copolymers

Amphiphilic biodegradable block copolymers [poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride)] were synthesized by the melt polycondensation of poly(ethylene glycol) and sebacic anhydride prepolymers. The chemical structure, crystalline nature, and phase behavior of the resulting copolymers were characterized with ¹H NMR, Fourier transform infrared, gel permeation chromatography, and differential scanning calorimetry. Microphase separation of the copolymers occurred, and the crystallinity of the poly(sebacic anhydride) (PSA) blocks diminished when the sebacic anhydride unit content in the copolymer was only 21.6%. ¹H NMR spectra carried out in CDCl₃ and D₂O were used to demonstrate the existence of hydrophobic PSA domains as the core of the micelle. In aqueous media, the copolymers formed micelles after precipitation from water‐miscible solvents. The effects on the micelle sizes due to the micelle preparation conditions, such as the organic phase, dropping rate of the polymer organic solution into the aqueous phase, and copolymer concentrations in the organic phase, were studied. There was an increase in the micelle size as the molecular weight of the PSA block was increased. The diameters of the copolymer micelles were also found to increase as the concentration of the copolymer dissolved in the organic phase was increased, and the dependence of the micelle diameters on the concentration of the copolymer varied with the copolymer composition. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1271–1278, 2006     

Laser light scattering study of the degradation of poly(sebacic anhydride) nanoparticles

Poly(sebacic anhydride) (PSA) is biocompatible and degradable in basic media. We micronized this water‐insoluble polymer into stable polymeric nanoparticles via a microphase inversion. Such PSA nanoparticles degraded much faster than bulk PSA. The influence of the surfactant, temperature, and pH on the degradation of the PSA nanoparticles was investigated by a combination of static and dynamic laser light scattering. Under each condition, the degradation rate was nearly constant up to a 75% weight loss; that is, the degradation was close to zero‐order. The degradation rate increased with the pH and temperature. Biomedical applications of such PSA nanoparticles are suggested. © 2001 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 39: 703–708, 2001     

Acrylate terpolymer in fabrication of medicated skin patches

An acrylate based pressure sensitive adhesive (PSA) was synthesized to design a drug‐in‐adhesive (DIA) type transdermal therapeutic system (TTS) for nitroglycerin used in the treatment of angina pectoris. 2‐Ethylhexyl acrylate (EHA), methyl methacrylate (MMA) and acrylic acid (AA) were used to synthesize the PSA by free radical solution polymerization. The effects of reaction time, reaction temperature, initiator concentration and solvent on polymerization were studied. The synthesized terpolymer was characterized by ¹H‐NMR, FT‐IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and also evaluated for intrinsic viscosity, refractive index, peel strength, moisture uptake and skin irritation potential. The PSA was used to develop DIA type patches of nitroglycerin. The patches were cast using solvent evaporation technique and dried at controlled temperature. The patches were evaluated for thickness uniformity, weight variation, peel strength and moisture pick‐up. The percent drug content and in vitro drug release was determined by high pressure liquid chromatography (HPLC) method. On the basis of in vitro release profile, patches were selected for in vitro skin permeation studies. The developed formulation TP‐1 (K = 24.892 mcg/cm²/hr) followed zero‐order rate kinetics and showed better skin permeation rate in comparison to the marketed TTS (MTTS) (K = 17.413 mcg/cm²/hr). TP‐1 was subjected to stability testing for a period of 1 year according to ICH guidelines. The patches were found to be stable and an expiry date of 2 years was predicted with storage at 25 °C or below. Copyright © 2001 John Wiley & Sons, Ltd.     

聚唾液酸-透明质酸接枝聚合物的合成及其在药物缓释载体中的应用

聚唾液酸(PSA)经环氧氯丙烷活化后,与透明质酸(HA)在碱性条件下反应合成了系列PSA-HA接枝聚合物(P¹~P⁵, PSA与HA质量比分别为1：1~5 ：1),合成率40%~89%,其结构经FT-IR,元素分析和SEM表征。以胰岛素为模型药物,将P²与胰岛素按2 ：1(m/m)混合时,包封率和载药率分别为85%和38%,平均粒径为3.2 μm。体外释药试验结果表明: P²对胰岛素有一定的体外缓释能力,在6 h内释药89%;在pH 1.2条件下的释药速度大于pH 7.4条件下的释药速度。     

Acrylate-based pressure sensitive adhesive in fabrication of transdermal therapeutic system

An acrylate-based pressure sensitive adhesive (PSA) was synthesized to incorporate in a design of a drug-in-adhesive (DIA) type transdermal therapeutic system (TTS) for nitrendipine and nicorandil in treatment of hypertension and angina pectoris, respectively. Solutions of 2-ethylhexyl acrylate (EHA; 85% w/w), methyl methacrylate (MMA; 10% w/w), acrylic acid (AA; 3% w/w) and vinyl acetate (VA; 2% w/w) in either ethyl acetate, acetone or methanol were polymerized under free radical conditions to synthesize the PSA. The effects of solvent, reaction time, initiator concentration and reaction temperature on polymerization were studied. The resultant copolymers were characterized by ¹H-NMR, IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and the intrinsic viscosities, refractive index, peel strength, moisture uptake and skin irritation potential were determined. The PSA was used to develop DIA type patches for delivery of nitrendipine and nicorandil. The TTS were evaluated for thickness, weight, peel strength, moisture uptake, in vitro release and in vitro skin permeation through guinea-pig skin. The copolymer found to effectively control the rate of drug release and the corresponding TTSs could be successfully employed in transdermal delivery of nitrendipine and nicorandil. Copyright © 2003 John Wiley & Sons, Ltd.