二氢杨梅素固体分散体的制备及其体内药动学研究

目的制备二氢杨梅素固体分散体,并研究其体内药动学。方法以PVP K30为载体,溶剂挥发法制备固体分散体,考察其溶解度和体外溶出。18只大鼠随机分为3组,分别灌胃给予原料药、物理混合物、固体分散体0.5%CMC-Na混悬液(150 mg/kg),于0.167、0.25、0.5、0.75、1、2、4、6、8、12 h取血,HPLC法测定血药浓度,计算主要药动学参数。结果二氢杨梅素制成固体分散体后以无定型状态存在,其表观溶解度提高了9.8倍,累积溶出度增加。与原料药、物理混合物比较,固体分散体tmax缩短(P<0.05),Cmax、AUC0~t、AUC0~∞升高(P<0.05,P<0.01),生物利用度提高了2.66倍。结论固体分散体技术可明显促进二氢杨梅素体内吸收,提高其生物利用度。     

Local abundance of Ixodes scapularis in forests: Effects of environmental moisture,vegetation characteristics,and host abundance

Ixodes scapularis is the primary vector of Lyme disease spirochetes in eastern and central North America, and local densities of this tick can affect human disease risk. We sampled larvae and nymphs from sites in Massachusetts and Wisconsin, USA, using flag/drag devices and by collecting ticks from hosts, and measured environmental variables to evaluate the environmental factors that affect local distribution and abundance of I. scapularis. Our sites were all forested areas with known I. scapularis populations. Environmental variables included those associated with weather (e.g., temperature and relative humidity), vegetation characteristics (at canopy, shrub, and ground levels), and host abundance (small and medium-sized mammals and reptiles). The numbers of larvae on animals at a given site and season showed a logarithmic relationship to the numbers in flag/drag samples, suggesting limitation in the numbers on host animals. The numbers of nymphs on animals showed no relationship to the numbers in flag/drag samples. These results suggest that only a small proportion of larvae and nymphs found hosts because in neither stage did the numbers of host-seeking ticks decline with increased numbers on hosts. Canopy cover was predictive of larval and nymphal numbers in flag/drag samples, but not of numbers on hosts. Numbers of small and medium-sized mammal hosts the previous year were generally not predictive of the current year’s tick numbers, except that mouse abundance predicted log numbers of nymphs on all hosts the following year. Some measures of larval abundance were predictive of nymphal numbers the following year. The mean number of larvae per mouse was well predicted by measures of overall larval abundance (based on flag/drag samples and samples from all hosts), and some environmental factors contributed significantly to the model. In contrast, the mean numbers of nymphs per mouse were not well predicted by environmental variables, only by overall nymphal abundance on hosts. Therefore, larvae respond differently than nymphs to environmental factors. Furthermore, flag/drag samples provide different information about nymphal numbers than do samples from hosts. Flag/drag samples can provide information about human risk of acquiring nymph-borne pathogens because they provide information on the densities of ticks that might encounter humans, but to understand the epizootiology of tick-borne agents both flag/drag and host infestation data are needed.     

Microspheres of essential oil in polylactic acid and poly(methyl methacrylate) matrices and their blends

This study is focussed on micro-encapsulation of essential oils in polylactic acid (PLA) and a poly(methyl methacrylate) (PMMA) matrix as well as blends of the same. Microspheres were prepared by the solvent evaporation technique and characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infra-red spectroscopy (FTIR). The encapsulation efficiencies and release profiles of the essential oils were studied by gas chromatography mass spectrometry (GC-MS) and head-space solid-phase microextraction GC-MS, respectively. Furthermore, the microspheres were tested for antibacterial activity against both Gram-negative and Gram-positive bacterial strains.

The results showed that the microspheres compositions (PLA/PMMA ratio) have significant effect on their characteristics. The process adopted for preparing the microspheres promoted formation of spherical particles at the sizes of 1.5–9.5?µm. The highest encapsulation efficiency of the prepared microspheres was observed in systems consisting of linalool (81.10?±?10.0?wt. % for PLA system and 76.0?±?3.3?wt. % for PMMA system). Confirmation was also made that the release rate of the microspheres was affected by the size of the same.     

丹参素钠-PLGA缓释微球的制备及药剂学性能评价

目的:优选丹参素钠-聚乳酸-羟基乙酸共聚物(PLGA)缓释微球的处方工艺并考察其药剂学性能。方法:采用W/O/O型乳化溶剂挥发法制备丹参素钠-PLGA微球,以载药量、包封率及收率为考察指标,通过单因素试验优选处方工艺,并考察其体外释药性能。采用激光粒度分析仪、扫描电子显微镜和X射线衍射法对该微球进行表征。结果:选取内水相体积300μL,PLGA质量浓度125 g·L~(-1),二氯甲烷-丙酮(3∶7),外油相为液体石蜡200 m L,加入正己烷6 m L,0.25%司盘80为乳化剂,1 400 r·min~(-1)搅拌4 h。丹参素钠-PLGA微球平均载药量(20.71±1.42)%,平均包封率(63.27±1.70)%,平均收率(99.10±0.83)%,体外累积释放率达98%需要120 h。平均粒径(71.72±1.71)μm,表面圆整光滑,内部含有蜂窝状孔洞。部分药物可能以晶体状态分散于载体材料中。结论:W/O/O型乳化溶剂挥发法成功制备了丹参素钠-PLGA微球,优选的处方工艺稳定合理,可为丹参素钠制剂的开发提供参考。     

黄芩素固体脂质纳米粒冻干粉的制备及体外释药性质的研究

目的制备黄芩素固体脂质纳米粒并冻干,考察其理化性质及体外释药特性。方法采用乳化蒸发-低温固化法,以包封率为考察指标,正交试验优化其处方并考察其粒径、形态、电位、多分散系数(PDI)及体外溶出。以外观、色泽、再分散性为考察指标筛选最佳冻干保护剂,利用差示扫描量热(DSC)、X射线衍射(XRD)、傅里叶红外光谱(FT-IR)分析药物在纳米粒中的存在状态。结果黄芩素固体脂质纳米粒外观呈球状体,分布均匀,平均粒径为(82.64±6.78)nm,PDI为0.242±0.013,Zeta电位为(-25.7±0.5)m V,包封率为(81.3±1.2)%,载药量为(7.16±0.14)%(n=3),以5%甘露醇作冻干保护剂效果较好,药物以无定形状态分散在脂质载体中,体外溶出实验表明黄芩素固体脂质纳米粒与原料药相比具有明显的缓释作用。结论乳化蒸发-低温固化法制得的黄芩素固体脂质纳米粒,粒径小,包封率高,稳定性好,工艺简单。     

厚朴总酚固体分散体不同制备方法的比较研究

比较研究厚朴总酚固体分散体不同制备方法之间的差异。分别使用热熔挤出法、溶剂蒸发法、熔融冷却法制备厚朴总酚Plastone S-630及HPC 2种辅料固体分散体。采用DSC,X-射线衍射评价所制备固体分散体中药物的分散状态;通过FT-IR分析药物与辅料之间可能存在的连接方式;最后通过加速稳定性-溶出试验比较3种工艺的稳定性差异。DSC及X-射线衍射结果显示3种工艺制备的固体分散体中药物均能以无定形态存在;FT-IR结果也无法区别3种工艺间的差异;加速稳定性-溶出试验表明HPC所制备的固体分散体稳定性明显优于Plastone S-630,同种辅料间热熔挤出技术制备的固体分散体稳定性要好于其他2种工艺。     

Cyrene™ as an Alternative Sustainable Solvent for the Preparation of Poly(lactic-co-glycolic acid) Nanoparticles

Toxic and environmental harmful organic solvents are widely applied to prepare poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NP) in standard preparation methods. Alternative non-toxic solvents suffer from disadvantages like high viscosity and plasticizing effects. To overcome these hurdles, Cyrene? as a new sustainable, non-toxic and low viscous solvent was used to formulate PLGA NPs. A new preparation method was developed and optimized. Small sized blank NPs around 220 nm with a narrow size distribution and highly negative charge (<?23 mV) were obtained. To test the application for drug delivery, the lipophilic model drug atorvastatin was encapsulated in high drug loads with comparable physicochemical characteristics as the blank NPs, and a total drug release within 24 h. No changes of the crystallinity or plasticizing effects could be observed. Highly purified NPs were obtained with a residual Cyrene? content <2.5%. Finally, the biocompatibility of Cyrene? itself and of the NPs formed in the presence of Cyrene? was demonstrated in a hen's egg test. Conclusively, the use of Cyrene? as solvent offers a simple, fast and non-toxic procedure for preparation of PLGA NPs as drug delivery systems circumventing the downsides of standard methods.     

Dissolution Improvement of Atorvastatin Calcium using Modified Locust Bean Gum by the Solid Dispersion Technique

The present research was aimed at the enhancement of the dissolution rate of atorvastatin calcium by the solid dispersion technique using modified locust bean gum. Solid dispersions (SD) using modified locust bean gum were prepared by the modified solvent evaporation method. Other mixtures were also prepared by physical mixing, co-grinding, and the kneading method. The locust bean gum was subjected to heat for modification. The prepared solid dispersions and other mixtures were evaluated for equilibrium solubility studies, content uniformity, FTIR, DSC, XRD, in vitro drug release, and in vivo pharmacodynamic studies. The equilibrium solubility was enhanced in the solid dispersions (in a drug:polymer ratio of 1:6) and other mixtures such as the co-grinding mixture (CGM) and kneading mixture (KM). Maximum dissolution rate was observed in the solid dispersion batch SD3 (i.e. 50% within 15 min) with maximum drug release after 2 h (80%) out of all solid dispersions. The co-grinding mixture also exhibited a significant enhancement in the dissolution rate among the other mixtures. FTIR studies revealed the absence of drug-polymer interaction in the solid dispersions. Minor shifts in the endothermic peaks of the DSC thermograms of SD3 and CGM indicated slight changes in drug crystallinity. XRD studies further confirmed the results of DSC and FTIR. Topological changes were observed in SEM images of SD3 and CGM. In vivo pharmacodynamic studies indicated an improved efficacy of the optimized batch SD3 as compared to the pure drug at a dose of 3 mg/kg/day. Modified locust bean gum can be a promising carrier for solubility enhancement of poorly water-soluble drugs. The lower viscosity and wetting ability of MLBG, reduction in particle size, and decreased crystallinity of the drug are responsible for the dissolution enhancement of atorvastatin. The co-grinding mixture can be a good alternative to solid dispersions prepared by modified solvent evaporation due to its ease of preparation and significant improvement in dissolution characteristics.     

地高辛-PLGA抗肿瘤纳米粒子的制备及其抗肿瘤活性的初步研究

目的 制备载地高辛的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒子,提高地高辛的生物利用度,降低其毒副作用.方法 建立测定地高辛-PLGA纳米粒子载药量和包封率的高效液相色谱法;采用乳化溶剂挥发法制备地高辛-PLGA纳米粒子,并通过单因素实验优化制备条件;采用噻唑蓝法评价地高辛和地高辛-PLGA纳米粒子的抗肿瘤能力.结果 以粒径为筛选条件的单因素实验结果表明,制备地高辛-PLGA纳米粒子的最佳条件为PLGA 30 mg,地高辛2 mg,二氯甲烷3 ml,聚乙烯醇质量分数0.5％,超声功率200 W.此制备条件下得到的地高辛-PLGA纳米粒子的粒径约231 nm,包封率为74.61％,载药量为5.37％,且其抗肿瘤活性优于地高辛,差异具有统计学意义(P＜0.05).结论 以PLGA为载体材料制备地高辛-PLGA纳米粒子可增强地高辛的抗肿瘤作用.