奥曲肽长效生物可降解微球的制备工艺研究

运用复乳法制备奥曲肽PLGA长效生物可降解微球,并用正交法优化微球制备工艺。利用HPLC、显微镜、激光粒度仪等对微球进行综合质量研究。结果表明,复乳法制备奥曲肽微球的最佳工艺参数为:内水相药物与中油相PLGA的质量比为1∶5,中油相PLGA的浓度为10%,外水相乳化剂为1%的22 000分子量聚乙烯(PVA)水溶液,中油相与外水相的体积比不小于1∶50,复乳化采用机械搅拌法,搅拌速度为1 200 r/min。在该工艺条件下制得的微球,包封率为35.1%,载药量为2.98%,平均粒径为26.3μm,微球外观圆整,形态良好。     

三七皂苷R1-PLGA纳米微球的制备及优化研究

应用高分子有机化合物聚乳酸-羟基乙酸共聚物[Poly(lactide-co-glycolide),PLGA]作为成膜材料包载三七皂苷R1制备纳米微球并寻求最优制备条件。采用复乳-溶剂挥发法制备纳米微球,使用高效液相色谱仪、激光粒度分析仪,测定包封率及粒径。采用正交实验设计,对影响包封率及粒径的因素分别进行五因素四水平正交实验。在PLGA浓度10mg/m L,内水相∶油相体积比为3∶10,外水相与初乳体积比为10∶1,第一次超声乳化时间10s,第二次超声乳化时间90s的条件下制备的微球包封率最为理想。若要获得最小粒径,则优化实验条件为:PLGA浓度20mg/m L,内水相∶油相体积比为2∶5,外水相与初乳体积比为2∶1,第一次超声乳化时间10s,第二次超声乳化时间120s。以PLGA为外壳材料可制备携三七皂苷R1纳米微球,并能获得其包封率及粒径制备的最优化条件。     

复相乳化法制备聚乳酸微胶囊及其性能考察

采用W/O/W复乳-溶剂蒸发法制备聚乳酸微球得到的最优制备条件:油水相比例5︰2、卡培他滨浓度为1.0mg/mL、外水相药液浓度5.0mg/mL,外水相体积20mL,几丁聚糖浓度为0.50%。以抗癌药卡培他滨为模型,考察了几丁聚糖浓度对聚乳酸微胶囊缓释性能的影响。结果表明:随着几丁聚糖浓度的增加,微囊释放速率相应降低。     

快速膜乳化法制备胸腺法新长效缓释微球

采用快速膜乳化技术结合溶剂蒸发法制备以生物可降解聚乳酸-羟基乙酸(PLGA)为载体的胸腺法新载药微球,考察了PLGA分子量、油相中PLGA和乳化剂浓度、外水相pH值和内水相体积等对微球包埋率和粒径的影响. 结果表明,制备粒径均一的PLGA载药微球的优化条件为：PLGA分子量51 kDa,油相中PLGA和乳化剂浓度为100和10 g/L,内水相体积0.5 mL,外水相pH值为3.5. 该条件下所制载药微球粒径均一性好(Span<0.7),药物包埋率高达80%以上,突释率24 h内低于20%,线性持续稳定释药时间长达30 d.     

单分散性PLGA磁性微球的制备及其缓释性

为获得单分散性PLGA磁性微球,以纳米四氧化三铁明胶分散液作为内水相(W1),PLGA(聚乳酸羟基乙酸共聚物)的二氯甲烷溶液作为油相(O),PVA(聚乙烯醇)水溶液作为外水相(W2),利用T型微通道并采用复合乳液法制备PLGA磁性微球,考察油相(O)质量浓度、外水相(W2)质量分数、流速比及油相与内水相体积比对微球制备的影响。借助FTIR、SEM、光学显微镜及VSM(振动样品磁强计)对磁性微球组分、形貌、粒径分布和磁学性能进行表征;并以阿司匹林作为药物模型进行缓释性测试。结果表明:油相中PLGA质量浓度为0.050kg/L,外水相(W2)中PVA质量分数为1%及2%,流速比v(W2)∶v(W1/O)=120∶1且体积比V(O)∶V(W1)=2∶1时可均匀成球,其粒径分布系数CV值仅为4.66%,表现出良好的单分散性;此时,比饱和磁化强度可达1.52emu/g,兼具优异顺磁性。制得的载药微球在60 h内表现出阶段性匀速释放,且有较好的磁响应性,有望用于磁响应性药物载体。     

快速膜乳化法制备载生长激素释放肽-6的PLGA微球

采用快速膜乳化法制备了聚(乳酸-羟基乙酸)(PLGA)微球,得到制备PLGA微球的优化条件为：过膜压力5 kPa,水相中PVA浓度19 g/L,油/水相体积比1:10,该条件下所制空白微球的平均粒径约为24 mm,粒径分布系数Span<0.7. 在此基础上制备载生长激素释放肽-6(GHRP-6)微球,油相乳化剂浓度2.5 g/L、外水相中NaCl浓度10 g/L条件下所制载GHRP-6微球包埋率最高可达85%,初乳制备方式对药物包埋率及体外释放行为均有较大影响,超声法制备的初乳所得微球内部结构紧密,药物包埋率较高(85%),但释药缓慢;而均质法制备的初乳所得微球内部结构疏松,药物包埋率较低(76.8%),但在体外释放更完全.     

两亲性刺突微球的制备及性能表征

以两亲性聚合物聚乙二醇-聚(乳酸儃乙醇酸)(mPEG儃PLGA)共聚物为材料,采用复乳法结合溶剂挥发法制备mPEG儃PLGA刺突微球,用其吸附蛋白多肽类药物,考察了膜材组分比、聚乳酸/羟基乙酸(LA/GA)摩尔比、内水相与油相体积比(W1/O)、油相与外水相体积比(O/W2)、固化条件等因素对微球的形貌结构及包埋率的影响.结果表明,优化的制备条件为:mPEG/PLGA分子量比1/19,LA/GA摩尔比50/50,W1/O/0.2,O/W2/1/10,固化搅拌速率500 r/min.该条件下所制微球刺突结构特征明显,包埋率高达70%以上,比表面积是普通光滑微球的14倍.     

CuZn-SOD乳酸-羟乙酸共聚物缓释微球的制备及体外、体内释放研究

目的 探讨CuZn-SOD包裹入乙酸-羟乙酸共聚物制备的药物微球的缓释效果。方法 采用复乳法制备CuZn-SOD乙酸-羟乙酸共聚物(PLGA)药物微球,分别用恒温摇瓶法和ELISA法检测体外和体内的释放效果。结果 有机相/分散相体积比、内水相体积、蛋白质浓度等因素影响微球的性质,由于聚合物的吸附作用,CuZn-SOD的体外释放呈明显的两段释放,释放不完全;体内释放显示微球制剂有一定的缓释效果。结论 该微球有比较好的缓释作用。     

正交设计优化尼美舒利NLC处方组成与制备工艺

运用高压均质法制备了加载尼美舒利的纳米结构脂质载体（Nanostructured Lipid Nanoparticles, NLC）,采用单因素设计考察了固液态油脂比、脂质用量、乳化剂用量、药脂比、均质压力和均质次数对纳米粒质量的影响。采用正交设计优化了制备条件。确定的最适宜制备方案为油酸与单硬脂酸甘油酯（glycerin monostearate,GMS）投料比为3:10,药脂比为1:40, TPGS用量为1.4 g,均质压力为90 MPa。依据最适宜处方制备的纳米粒粒径为132.6± 1.4 nm,包封率为82.35±1.23%。扫描电镜显示所制备纳米粒呈类球形,体外释放实验表明其释放行为符合Higuchi模型。     

伊维菌素缓释微球注射液制备工艺研究

以乳化溶剂挥发法制备伊维菌素(IVM)聚乳酸(PLA)微球,用该微球制备注射液并进行质量控制研究。采用Central Composite试验设计,对微球制备中的搅拌速度、投料比IVM:PLA、聚乙烯醇浓度3个因素进行响应面优化;采用L16(34)正交实验对助悬体系进行优化;制备IVM缓释微球注射液并进行质量评价。研究结果表明：优化后的搅拌速度为651 r/min,投料比为7:16,PVA浓度为1.47%,此条件下微球载药率为29.4%;优化后的助悬体系为微球粒径80μm,微球、吐温20与羟甲基纤维素钠含量分别为2.5%、1.5%、1%,在此条件下注射液沉降体积比为91.5%;经测定注射液的平均pH为7.2,体外20d内可以平稳释放,达到缓释效果,稳定性良好,这一研究过程为IVM缓释微球注射液的工业制备及在临床上安全应用奠定了一定基础。     

Preparation and evaluation of poly(3‐hydroxybutyrate) microspheres containing bovine serum albumin for controlled release

The utility of the Poly(3‐hydroxybutyrate) (PHB) to encapsulate and control the release of bovine serum albumin (BSA), via microspheres, was investigated. Various preparing parameters, including polymer concentration in oil phase, emulsification concentration in external water phase, volume ratio of inner water phase to oil phase, and volume ratio of primary emulsion to external water phase were altered during the microspheres production. The effects of these changes on the morphological characteristics of the microspheres, size of the microspheres, drug loading, encapsulation efficiency, and drug release rates were examined. The diameter of the microspheres ranged from 6.9 to 20.3 μm and showed different degrees of porous structure depending on the different preparation parameters. The maximum and minimum BSA encapsulation efficiency within the polymeric microspheres were 69.8 and 7.5%, respectively, varying with preparation conditions. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media. The initial BSA burst release from 8.9 to 63.1% followed by constant slow release for 28 days was observed for BSA from BSA‐loaded microspheres and followed the Higuchi matrix model. So, the release behavior of microspheres showed the feasibility of BSA‐loaded microspheres as controlled release devices. Pristine BSA, pristine PHB microspheres, and BSA‐loaded microspheres were analyzed by Fourier transform infrared spectrophotometer, which indicated no interaction between BSA and PHB. Differential scanning calorimetry on BSA‐loaded microspheres indicated a molecular level dispersion of BSA in the microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

单分散性PLGA磁性微球制备及其缓释性研究

为获得单分散性PLGA磁性微球,文中以纳米四氧化三铁明胶分散液作为内水相(W1),PLGA（聚乳酸羟基乙酸共聚物）的二氯甲烷溶液作为油相(O),PVA（聚乙烯醇）水溶液作为外水相(W2),利用T型微通道并采用复合乳液法制备PLGA磁性微球,考察流速比和油相与内水相体积比对微球制备的影响。借助FTIR、SEM及VSM（振动样品磁强计）对磁性微球组分、形貌、粒径分布和磁学性能进行表征;并以阿司匹林作为药物模型进行缓释性测试。结果表明：流速比v(W2):v(W1/O)=120:1且体积比V(O):V(W1)=2:1时可均匀成球,其粒径分布系数CV值仅为4.66%,表现出良好单分散性;此时比饱和磁化强度可达1.52emu/g,兼具优异顺磁性。制得的载药微球在60h内表现出阶段性匀速释放,且有较好磁响应性,有望用于磁响应性药物载体。     

Preparation of magnetic poly(lactic‐co‐glycolic acid) microspheres featuring monodispersity and controllable particle size using a microchannel device

Poly(lactic‐co‐glycolic acid) (PLGA) microspheres prepared using a traditional solvent evaporation or double emulsification method are usually polydisperse with an uncontrollable particle size distribution, which brings about poor application performance. In our research, monodisperse magnetic PLGA microspheres were prepared using a microchannel device based on a water‐in‐oil‐in‐water composite emulsion. The composite emulsion was formed by injecting a dichloromethane–gelatin water‐in‐oil emulsion into a microchannel together with an external water phase, i.e. poly(vinyl alcohol) (PVA) aqueous solution. Mean particle size control of the microspheres was executed using the osmotic pressure difference between internal and external aqueous phases caused by regulating NaCl concentration in PVA aqueous phase. It is found that monodisperse magnetic PLGA microspheres with high magnetic responsiveness can be successfully prepared combining the microchannel device with composite emulsion method. Mean particle size of the microspheres with coefficient of variation value below 4.72% is controllable from 123 to 203 µm depending on the osmotic pressure. The resulting samples have pyknotic and smooth surfaces, as well as spherical appearance. These monodisperse magnetic PLGA microspheres with good superparamagnetism and magnetic mobility have potential use as drug carriers for uniform release and magnetic targeting hyperthermia in biological fields. © 2015 Society of Chemical Industry     

聚砜微球的双乳液法制备及其吸附特性

根据相转化原理,采用双乳液法制备了聚砜微球,扫描电镜观察表明制得的聚砜微球粒径较为均一,且表面致密.在微球制备过程中,二甲基甲酰胺中的聚砜浓度、两乳液中的连续相（石蜡）与分散相（DMF或水）的体积比对微球的成球性能有较大影响.将聚砜微球应用于利尿剂组分的吸附,表明其对酸性利尿剂氟咯噻咪和碱性利尿剂氨苯蝶啶有较好吸附.     

Preparation of magnetic poly(lactic‐co‐glycolic acid) microspheres with a controllable particle size based on a composite emulsion and their release properties for curcumin loading

Because of their unique magnetic features and good biocompatibility, magnetic poly(lactic‐co‐glycolic) acid (PLGA) microspheres have great application potential in magnetic targeted drug‐delivery systems. In this research, magnetic PLGA microspheres with controllable particle sizes were successfully prepared from a composite emulsion with a T‐shaped microchannel reactor. A water‐in‐oil‐in‐water composite emulsion was generated by the injection of a dichloromethane/gelatin water‐in‐oil initial emulsion into the microchannel together with a coating aqueous phase, that is, the aqueous solution of glucose and poly(vinyl alcohol). The mean particle size of the microspheres could be controlled by the manipulation of the osmotic pressure difference between the internal and external aqueous phases via changes in the glucose concentration. Curcumin, a drug with an inhibitory effect on tumor cells, was used to exemplify the release properties of the magnetic PLGA microspheres. We found that the mean particle size of the microspheres ranged from 16 to 207 μm with glucose concentrations from 0 to 20 wt %. The resulting microspheres showed a rapid magnetic response, good superparamagnetism, and a considerable magnetocaloric effect, with a maximum magnetic entropy of 0.061 J·kg^?1·K^?1 at 325 K. An encapsulation efficiency of up to 77.9% was achieved at a loading ratio of 3.2% curcumin. A release ratio of 72.4% curcumin from the magnetic PLGA microspheres was achieved within 120 h in a phosphate‐buffered solution. The magnetic PLGA microspheres showed potential to be used as drug carriers for magnetic targeted tumor therapy. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43317.     

阿司匹林-壳聚糖缓释微球的制备和释药性能研究

采用乳化交联法制备阿司匹林-壳聚糖缓释凝胶微球,通过透析实验检测微球的体外释放特性。应用正交实验设计,考察了壳聚糖浓度,搅拌速度,阿司匹林/壳聚糖质量比,交联时间对微球制备的影响。体外释放实验表明,壳聚糖微球前5个小时的释放符合SRP的释药行为。以5个小时的体外释放总量为指标进行直观分析,交联时间对5小时的体外释放总量影响最大。     

Extraction of alcohol using emulsion liquid membrane consisting of paraffin oil as an organic phase and lecithin as a surfactant

BACKGROUND: This paper reports on the use of a liquid emulsion membrane involving paraffin light oil as membrane phase and lecithin as surfactant for the extraction of alcohol from anthocyanin extract and simulated pineapple wine. RESULTS: The extraction of alcohol was found to depend on the many factors such as surfactant concentration, contact time, stirring speed, stirring time, and ratio of membrane emulsion to feed volume. Results showed that optimum conditions for maximum alcohol extraction (25%) were lecithin concentration 3%, contact time 20 min, stirring speed 250 rpm and ratio of membrane emulsion to feed volume 1:2. Multistage extraction using this liquid emulsion membrane was found to completely remove alcohol from anthocyanin extract and from simulated pineapple wine in seven stages and five stages, respectively. CONCLUSION: This liquid emulsion membrane was found to be a useful method for the extraction of alcohol from aqueous feed. Copyright © 2009 Society of Chemical Industry