新型羟基脲化合物Ⅲ_5的镇痛抗炎作用

目的探讨新型羟基脲类化合物Ⅲ5的镇痛及抗炎作用。方法采用小鼠热板法和扭体法证明化合物Ⅲ5的镇痛作用;采用二甲苯致小鼠耳肿胀,醋酸致毛细血管通透性增加,蛋清致大鼠足趾肿胀模型证明化合物Ⅲ5的抗炎作用。结果化合物Ⅲ5能延长小鼠的热痛阈值,能延长造模后小鼠第一次出现扭体反应的潜伏期并减少15 min内扭体反应出现的次数;能显著抑制耳肿胀,醋酸对毛细血管的通透性以及不同时间点大鼠的足趾肿胀度。结论化合物Ⅲ5具有明显的镇痛抗炎作用。     

姜百片对大鼠醋酸损伤胃溃疡模型的干预作用

目的研究一种由高良姜、香附、百合和乌药提取物制成的复方中药姜百片对大鼠醋酸损伤胃溃疡模型胃黏膜的保护作用。方法采用醋酸注射法制作大鼠醋酸胃溃疡模型,将动物分为模型组、雷尼替丁阳性对照组（0.108g·kg^-1·d^-1）、姜百片高（2.16g·kg^-1·d^-1）、中（1.08g·kg^-1·d^-1）、低（0.54g·kg^-1·d^-1）剂量组,连续口服给药10d后处死并解剖大鼠,测量胃黏膜溃疡面的长短径（L和H）,按照公式S=πLH/4计算溃疡面积,用试剂盒测定损伤部位表皮生长因子（EGF）和血管内皮生长因子（VEGF）的水平。结果与模型组相比,该复方中药的高（2.16g·kg^-1·d^-1）、中（1.08g·kg^-1·d^-1）、低（0.54g·kg^-1·d^-1）剂量可以显著减小醋酸损伤大鼠的溃疡面积（P〈0.05）,并可显著提高醋酸损伤部位组织的表皮生长因子（EGF）（P〈0.05）和血管内皮生长因子（VEGF）（P〈0.05）的水平。结论姜百片具有抗醋酸损伤型胃溃疡的作用,其作用机制可能与提高组织的EGF和VEGF水平等有关。     

肠腑康胶囊镇痛抗炎及抗溃疡性结肠炎作用的实验研究

目的观察肠腑康胶囊的镇痛、抗炎及抗溃疡性结肠炎作用。方法采用甩尾法和扭体法进行镇痛作用的研究,抗炎作用采用二甲苯法及腹腔通透性法,溃疡性结肠炎用乙酸造模,灌胃给药观察治疗作用。结果与对照组比较,肠腑康胶囊可延长小鼠甩尾时间,并可减少动物扭体次数;对二甲苯致小鼠耳廓肿胀有明显的抑制作用,对小鼠腹腔毛细血管通透性有明显的抑制作用;对乙酸性豚鼠结肠炎模型,与模型组比较,豚鼠的状态有一定的改变,溃疡面积显著减小。结论肠腑康胶囊具有一定的止痛、抗炎作用;对乙酸性豚鼠直肠溃疡性结肠炎有一定的治疗作用。     

消肿镇痛巴布膏剂药效学试验研究

目的:研究消肿镇痛巴布膏剂在镇痛、抗炎、活血化瘀方面的药效学作用.方法:采用传统消肿镇痛贴剂为参比,以小鼠光电甩尾试验和醋酸扭体试验研究其镇痛作用,以小鼠皮肤毛细血管通透性试验观察其抗炎作用,以大鼠自身血所致足趾肿胀试验研究其活血化瘀作用.结果:消肿镇痛巴布膏剂可以明显延长小鼠的甩尾潜伏期,减少小鼠扭体次数,并明显抑制二甲苯所致小鼠皮肤毛细血管通透性亢进以及自身血所致大鼠足趾肿胀.结论:经皮给予消肿镇痛巴布膏剂具有明显的抗炎镇痛及活血化瘀作用,效果优于传统贴剂.     

槲皮苷防治溃疡性结肠炎的药效学研究

目的 观察槲皮苷防治溃疡性结肠炎及抗炎、镇痛、止泻等药效。     

接活跌打膏抗炎镇痛作用考察

考察接活跌打膏的抗炎及镇痛作用。方法：采用角叉菜胶致大鼠足趾肿胀法、棉球致大鼠肉芽肿法观察接活跌打膏的抗炎作用;小鼠热板法和小鼠醋酸扭体法观察接活跌打膏的镇痛作用。结果：和模型组比较,在给药后2h,接活跌打膏28g·kg^-1和14g·kg^-1药材剂量组可显著抑制角叉菜胶致大鼠足趾肿胀（P〈0．05）;和正常对照组比较,接活跌打膏28g·kg^-1和14g·kg^-1药材剂量组能抑制大鼠棉球肉芽组织干重（P〈0．05）;和正常对照组比较,接活跌打膏28g·kg^-1和14g·kg^-1药材剂量组能显著减少醋酸引起的小鼠扭体反应次数,在给药后60min,能延长小鼠热板痛阈值（P〈0．05或P〈0．01）。结论：接活跌打膏具有显著的抗炎和镇痛作用。     

白芍醇提液抗炎镇痛作用研究

目的:观察白芍醇提液的抗炎镇痛作用。方法:抗炎作用采用小鼠耳肿胀法以及腹腔毛细血管渗透法,镇痛作用采用光热测痛法以及醋酸扭体法。结果:白芍醇提液对二甲苯致小鼠耳肿胀以及醋酸致小鼠腹腔毛细血管通透性增加均有一定的抑制作用,并能显著降低光热法致痛小鼠的痛阈值,延长醋酸致小鼠扭体反应潜伏期以及扭体次数。结论:白芍醇提液具有一定的抗炎镇痛作用。     

红葱乙醇提取物的抗炎镇痛及壮阳作用

目的：研究红葱乙醇提取物（ EEEP）的抗炎、镇痛及壮阳作用。方法将动物随机分为空白组,阳性对照组,EEEP高、中、低剂量组,采用二甲苯致耳肿胀、致毛细血管通透性增加模型,醋酸扭体法疼痛模型,连续给药4 d,计算耳肿胀抑制率、染料渗出抑制率、扭体反应抑制率;采用正常雄性大鼠模型,连续给药7 d,记录扑捉潜伏期、扑捉次数、射精次数。结果95％,70％EEEP的低、中、高3个剂量组与空白组相比,分别对二甲苯致小鼠耳肿胀、致皮肤毛细血管通透性增加以及小鼠扭体反应有明显的抑制作用;但70％EEEP对扑捉潜伏期、扑捉次数、射精次数无显著影响,但随着给药剂量的增加,呈现出扑捉次数、射精次数增加的趋势。结论 EEEP具有明显的抗炎、镇痛作用,并且对正常雄性大鼠的一般性行为有增强的趋势。     

妇安康胶囊对慢性盆腔炎的保护作用

目的探讨妇安康胶囊对慢性盆腔炎的作用。方法采用小鼠耳肿胀法和大鼠棉球肉芽肿法,观察妇安康胶囊的抗炎作用;采用小鼠热板法和扭体法,观察妇安康胶囊的镇痛作用;采用大肠杆菌致慢性盆腔炎模型,观察妇安康胶囊对大肠杆菌致慢性盆腔炎的大鼠子宫肿胀率、血清中SOD活性和MDA含量、子宫组织病理学的变化。结果妇安康胶囊（1.4、2.8 g·kg^-1）对小鼠的耳肿胀度和大鼠棉球肉芽增生有一定的抑制作用;妇安康胶囊（1.4、2.8 g·kg^-1）可以延长小鼠热板潜伏期和减少扭体次数。在大肠杆菌致慢性盆腔炎模型大鼠上,妇安康胶囊（1.2、2.4 g·kg^-1）可抑制大鼠子宫肿胀率、升高SOD活性、降低MDA含量、改善子宫病理组织学的变化。结论妇安康胶囊对大肠杆菌致慢性盆腔炎大鼠有一定的保护作用。     

清热糖浆的药理作用研究

目的观察清热糖浆的抗菌、抗炎、解热、镇痛和镇咳作用。方法试管法观察抗菌作用,醋酸法考察小鼠毛细血管通透性;2,4-二硝基苯酚致热法观察对大鼠的解热作用;扭体法和甲醛致痛法观察镇痛作用;氨水刺激法考察镇咳作用。结果清热糖浆对4株临床分离菌株均有抑制作用;能降低小鼠毛细血管通透性;对2,4- 二硝基苯酚致热大鼠有明显退热作用;明显减少醋酸致小鼠扭体次数,减少甲醛所致大鼠疼痛反应次数;减少氨水致咳嗽次数。结论清热糖浆有抗茵、抗炎、解热、镇痛和镇咳作用。     

姜黄素-PLGA纳米粒提高口服给药生物利用度的研究

目的 研究乳酸/羟基乙酸共聚物（PLGA）纳米粒子提高姜黄素口服生物利用度。方法 采用乳液挥发法制备姜黄素-PLGA纳米粒;通过透射电镜（transmission electron microscope,TEM）观察纳米粒形态;采用动态光散射法（dynamic light scattering,DLS）测定纳米粒大小、表面电位（Zeta电位）;考察药物的体外稳定性以及药物释放行为;以大鼠口服灌胃给药方式考察姜黄素和姜黄素-PLGA纳米粒的体内药物生物利用度。结果 姜黄素-PLGA纳米粒粒度分布均匀,平均粒径大小约200 nm;姜黄素-PLGA纳米粒具有较高的载药量和包封率以及稳定性,体外药物释放实验结果显示具有一定的缓释效果;口服灌胃100 mg·kg^-1姜黄素和姜黄素-PLGA纳米粒,给药30 min之后,姜黄素-PLGA纳米粒给药组的血药浓度水平显著高于姜黄素组（P〈0.05）,药物生物利用度提高到原来的5.2倍。结论 姜黄素-PLGA纳米粒可以有效的提高姜黄素稳定性和口服给药生物利用度。     

Fabrication,characterization and in vitro evaluation of poly(D,L-lactide-co-glycolide) microparticles loaded with polyamidoamine–plasmid DNA dendriplexes for applications in nonviral gene delivery

We report, for the first time, on the preparation, characterization and in vitro testing of poly(D,L-lactide-co-glycolide) (PLGA) microparticles loaded with polyamidoamine (PAMAM)–plasmid DNA (pDNA) dendriplexes. Loading of pDNA into the PLGA microparticles increased by 150% when pDNA was first complexed with PAMAM dendrimers relative to loading of pDNA alone. Scanning electron microscopy (SEM) showed that the presence of PAMAM dendrimers in the PLGA microparticles created porous features and indentations on the surface of the microparticles. Loading PLGA microparticles with PAMAM–pDNA dendriplexes lowered the average PLGA microparticle size and changed the surface charge of the microparticles from negative to positive when compared to PLGA microparticles loaded with pDNA alone. The zetapotential and buffering capacity of the microparticles increased as the generation of the PAMAM dendrimer loaded in the PLGA microparticles increased. Gel electrophoresis assays showed that all the PLGA microparticle formulations were able to entrap the pDNA within the PLGA matrix. There was no significant difference in the cytotoxicity of PLGA microparticles loaded with PAMAM–pDNA dendriplexes when compared to PLGA microparticles loaded with pDNA alone. Furthermore, and in contrast to PAMAM dendrimers alone, the generation of the PAMAM dendrimer loaded in the PLGA microparticles had no significant impact on cytotoxicity or transfection efficiencies in human embryonic kidney (HEK293) or Monkey African green kidney fibroblast-like (COS7) cells. The transfection efficiency of PLGA microparticles loaded with generation 3 (G3) PAMAM–pDNA dendriplexes was significantly higher than PLGA microparticles loaded with pDNA alone in HEK293 and COS7 cells. PLGA microparticles loaded with G3 PAMAM–pDNA dendriplexes generated equivalent transfection efficiencies as (G3 to G6) PAMAM–pDNA dendriplexes alone in COS7 cells when the transfection was carried out in serum containing media. The delivery system developed in this report has low toxicity, high pDNA loading efficiencies and high transfection efficiencies that are not reduced in the presence of serum. A delivery system with these characteristics is expected to have significant potential for translational applications. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:368–384, 2010     

A biodegradable drug delivery system for the treatment of postoperative inflammation

Cataract surgery is often performed in patients suffering from associated pathologies. Our goal is to develop a biodegradable drug delivery system (DDS) combined with the artificial intraocular lens (IOL). DDS were manufactured using poly(D,L-lactide-co-glycolide), or PLGA, and were loaded with triamcinolone acetonide (TA). The loading capacity was approximately 1050 microg of TA per DDS. The higher the molecular weight of PLGA (34,000, 48,000 and 80,000Da), the slower was the release of TA in vitro. Cataract surgery was performed on the right eye of rabbits. IOL was inserted with (i) no DDS, (ii) unloaded DDS PLGA48000, (iii) one loaded DDS PLGA48000, (iv) two loaded DDS. The number of inflammatory cells and the protein concentration were measured in the aqueous humor (AH). Unloaded DDS showed good ocular biocompatibility. One DDS PLGA48000 loaded with TA significantly reduced postoperative ocular inflammation. Two loaded DDS PLGA48000 was even more effective in inhibiting such inflammation. On long-term observation (days 63 and 84), reduction of inflammation could be obtained by insertion of one DDS PLGA48000 and a second DDS PLGA80000. Therefore, our "all in one" system is very promising since it could replace oral treatment and reduce the number of intraocular injections.     

GM-1PLGA肌注微球的制备及其体外释药评价

目的 研究以聚乳酸羟基乙酸共聚物为囊材,制备长效缓释的单唾液酸四己糖神经节苷脂微球制剂.方法运用复乳溶剂挥发法,考虑多个条件对制备工艺的影响,并采用正交设计对处方进行优化.测定微球的载药量、包封率和释放曲线.结果制备得到的GM-1微球粒径大小均匀,球形致密圆整,微球粒径为(8.2±6.0)μm,载药量和包封率分别为18...     

复乳法制备蛋白质药物PLGA微球的影响因素

PLGA共聚物具有良好的生物相容性,是目前制备微球最常用的一类可生物降懈的高分子材料。复乳法是制备蛋白质药物PLGA微球最常用的方法。综述复乳法制备蛋白质药物PLGA微球过程中,处方、工艺等因素对微球粒径、包封率和释放特性以及蛋白质稳定性的影响。     

Long circulating nanoparticles of etoposide using PLGA‐MPEG and PLGA‐pluronic block copolymers: characterization,drug‐release,blood‐clearance,and biodistribution studies

The anti‐leukemic drug, etoposide (ETO), has variable oral bioavailability ranging from 24–74% with a short terminal half‐life of 1.5 h i.v. necessitating continuous infusion for 24–34 h for the treatment of leukemia. In the present study, etoposide‐loaded PLGA‐based surface‐modified nanoparticles (NPs) with long circulation were designed as an alternative to continuous i.v. administration. PLGA‐mPEG and PLGA‐PLURONIC copolymers were synthesised and used to prepared ETO‐loaded NPs by high‐pressure homogenization. The mean particle size of ETO‐loaded PLGA‐MPEG nanoparticles was 94.02±3.4 nm, with an Entrapment Efficiency (EE) of 71.2% and zeta potential value of −6.9±1.3 mV. ETO‐loaded PLGA‐pluronic nanoparticles had a mean particle size of 148.0±2.1 nm, an EE of 73.12±2.7%, and zeta potential value of −21.5±1.6 mV. In vitro release of the pure drug was complete within 4 h, but was sustained up to 7 days from PLGA‐mPEG nanoparticles and for 5 days from PLGA‐pluronic nanoparticles. Release was first order and followed non‐Fickian diffusion kinetics in both instances. ETO and ETO‐loaded PLGA nanoparticles labeled with ^99mTc were used in blood clearance studies in rats where the two coated NPs, ^99mTc‐ ETO‐PLGA‐PLU NP and ^99mTc‐ ETO‐PLGA‐mPEG NP, were found to be available in higher concentrations in the circulation as compared to the pure drug. Biodistribution studies in mice showed that ETO‐loaded PLGA‐MPEG NP and PLGA‐PLURONIC NP had reduced uptake by the RES due to their steric barrier properties and were present in the circulation for a longer time. Moreover, the NPs had greater uptake in bone and brain where concentration of the free drug, ETO, was negligible. Drug delivered from these NPs could result in a single i.v. injection that would release the drug for a number of days, which would be potentially beneficial and in better control of leukemia therapy. Drug Dev Res 71: 228–239, 2010. © 2010 Wiley‐Liss, Inc.     

包载荧光探针香豆素-6的PLGA纳米粒的制备

目的以生物可降解材料聚乳酸,羟基乙酸共聚物（PLGA）为材料,制备包载荧光探针香豆素-6纳米粒,并进行处方优化。方法采用乳化-溶剂挥发法制备香豆素-6。PLGA纳米粒,以利用率和包封率为考察指标,正交试验对处方进行优化。结果制得香豆素-6纳米粒的包封率为51．6％,利用率为81．9％,平均粒径135nm,香豆素-6体外72h泄漏率低于2％。结论香豆素-6 PLGA纳米粒制备工艺简便可行,香豆素-6可作为荧光探针,用于纳米粒的动物体内示踪及靶向性研究。     

Comparative evaluation of in vitro parameters of tamoxifen citrate loaded poly(lactide-co-glycolide), poly(epsilon-caprolactone) and chitosan nanoparticles

Tamoxifen (TAM), the clinical choice for the antiestrogen treatment of advanced or metastatic breast cancer, was formulated in nanoparticulate carrier systems in the form of poly(lactide-co-glycolide) (PLGA), poly-epsilon-caprolactone (PCL) and chitosan (CS) nanoparticles. The PLGA and PCL nanoparticles were prepared by a nanoprecipitation technique whereas the CS nanoparticles were prepared by the ionic gelation method. Mean particle sizes were under 260 nm for PLGA and PCL nanoparticles and around 400 nm for CS nanoparticles. Polydispersity indices were less than 0.4 for all formulations. Zeta potential values were positive for TAM loaded nanoparticles because of the positive charge of the drug. Drug loading values were significantly higher for PCL nanoparticles when compared to PLGA and CS nanoparticles. All nanoparticle formulations exhibited controlled release properties. These results indicate that TAM loaded PLGA, PCL and CS nanoparticles may provide promising carrier systems for tumor targeting.     

Heparin Immobilized Porous PLGA Microspheres for Angiogenic Growth Factor Delivery

Purpose Heparin immobilized porous poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres were prepared for sustained release of basic fibroblast growth factor (bFGF) to induce angiogenesis.Materials and Methods Porous PLGA microspheres having primary amine groups on the surface were prepared using an oil-in-water (O/W) single emulsion method using Pluronic F-127 as an extractable porogen. Heparin was surface immobilized via covalent conjugation. bFGF was loaded into the heparin functionalized (PLGA-heparin) microspheres by a simple dipping method. The bFGF loaded PLGA-heparin microspheres were tested for in vitro release and in vivo angiogenic activity.Results PLGA microspheres with an open-porous structure were formed. The amount of conjugated amine group onto the microspheres was 1.93 ± 0.01 nmol/mg-microspheres, while the amount of heparin was 95.8 pmol/mg-microspheres. PLGA-heparin microspheres released out bFGF in a more sustained manner with a smaller extent of initial burst than PLGA microspheres, indicating that surface immobilized heparin controlled the release rate of bFGF. Subcutaneous implantation of bFGF loaded PLGA-heparin microspheres in mice significantly induced the formation of new vascular microvessels.Conclusions PLGA microspheres with an open porous structure allowed significant amount of heparin immobilization and bFGF loading. bFGF loaded PLGA-HP microspheres showed sustained release profiles of bFGF in vitro, demonstrating reversible and specific binding of bFGF to immobilized heparin. They also induced local angiogenesis in vivo in an animal model.     

Pharmacokinetics and in vitro and in vivo correlation of huperzine A loaded poly(lactic-co-glycolic acid) microspheres in dogs

The purpose of this study was to investigate the pharmacokinetics and in vitro/in vivo correlation (IVIVC) of huperzine A loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in dogs. Several huperzine A loaded PLGA microspheres were prepared by an O/W method and three of them (single dose) were injected intramuscularly (i.m.) or subcutaneously (s.c.) to five beagle dogs, respectively. With the increase of the molecular weight of PLGA and the particle size of microspheres, the in vitro and in vivo release periods of huperzine A were prolonged. After s.c. injection, the release of huperzine A from microspheres was faster than that after i.m. injection. The IVIVC models of huperzine A loaded PLGA microspheres were established successfully and after i.m. administration the linear relationship between the in vitro and the in vivo releases was better than that after s.c. administration. It was also found when the particle size of the microspheres was smaller; the values of correlation coefficient were higher.