氟尿嘧啶壳聚糖缓释剂瘤内注射治疗小鼠肝癌的实验研究

目的探讨生物可降解氟尿嘧啶壳聚糖注射胶用于肿瘤内局部给药的抗肿瘤活性,为临床应用提供实验依据.方法80只小鼠随机分为8组,分别瘤内注射氟尿嘧啶壳聚糖胶、壳聚糖空白胶、氟尿嘧啶注射液及腹腔注射氟尿嘧啶注射液.观察荷瘤鼠肿瘤生长、荷瘤鼠给药前、后血象及给药后肿瘤组织凋亡指数.结果瘤内注射氟尿嘧啶壳聚糖缓释液组小鼠(60mg/kg,qw×2)肿瘤生长缓慢,瘤体明显小于氟尿嘧啶腹腔注射给药组,并呈现良好的量效关系.结论瘤内应用氟尿嘧啶壳聚糖缓释剂的抗肿瘤效果优于局部和全身单纯氟尿嘧啶给药,有重要研发价值.     

水飞蓟素缓释滴丸的研制及其体外释放特性

目的:研究水飞蓟素缓释滴丸的处方和工艺,并对其体外释放特性进行了评价.方法:采用联合载体材料即聚乙二醇6000和泊洛沙姆188为速释性固体分散体载体材料,硬脂酸为缓释性骨架材料;熔融法制备水飞蓟素缓释滴丸,考察了滴丸成型的影响因素;并与市售片剂进行了释放度比较.结果:选择处方组成为水飞蓟素:聚乙二醇6000:泊洛沙姆188:硬脂酸(1:2:1:1.5);滴头直径为2.3 mm/4.1 mm,滴距为6 cm,滴速为40滴·min-1;该缓释滴丸10 h的最大累积溶出百分率可达92.5%.结论:所制得水飞蓟素缓释滴丸具有良好的缓释效果,为研发水飞蓟素新制剂提供参考.     

利多卡因脂质体的初步研制及其质量评价

目的研制利多卡因的一种缓释长效制剂-利多卡因脂质体,并对其制备工艺进行研究,且评价其质量.方法以磷脂、胆固醇为膜材,采用乙醚注入法和薄膜分散法制备利多卡因脂质体并对制剂的形态学、载药量及包封率等进行研究.结果利多卡因脂质体为乳白色、近透明的胶体溶液.光镜下呈双同心球体满视野.测得其包封率分别为22.7%和21.6%.结论乙醚注入法和薄膜分散法两种制备工艺所得的利多卡因脂质体无明显区别.     

复方丹参缓释片钙拮抗作用及体外缓释作用的综合评价

目的　采用4 5Ca跨膜内流测量技术确认复方丹参缓释片及其组分对电压依赖性钙通道(potentital depen-dent Ca2 channel,PDC)钙离子内流的拮抗作用,探讨其体外缓释作用的综合评价方法。方法　将缓释制剂释放度测定法与4 5Ca跨膜内流测量技术相结合,在规定的时间点取复方丹参缓释片体外释放样品测定。取Wistar大鼠胸主动脉,分成小段依次置于复合电解质溶液(PSS)、“4 5Ca- PSS 药”混合液、“4 5Ca- PSS高钾 药”混合液中,取出动脉环用冷EGTA洗涤,消化。用液体闪烁计数器测量复方丹参缓释片、其组分及体外释放样品的放射性活度。结果　复方丹参缓释片、复方丹参片、丹参脂溶性部位、丹参水溶性部位、三七总皂苷、丹参酮 A、丹参素、原儿茶醛、人参皂苷Rb1和三七皂苷R1均有极显著的钙拮抗作用,冰片有显著的钙拮抗作用;复方丹参缓释片4 h开始有显著钙拮抗作用,6 h后有极显著钙拮抗作用,而自制复方丹参片1h即有显著钙拮抗作用,2 h后有极显著钙拮抗作用。结论　复方丹参缓释片为钙拮抗剂;丹参脂溶性部位、丹参水溶性部位、三七总皂苷为钙拮抗有效部位,丹参酮 A、丹参素、原儿茶醛、人参皂苷Rb1、三七皂苷R1和冰片为钙拮抗有效成分;与自制复方丹参片比较,复方丹参缓释片具有延缓起效作用,通过体外释放样品钙拮抗作用测定,可以对治疗心血管疾病的中药及天然药物制剂的体外缓释作用进行综合评价。     

人工神经网络预测别嘌醇HP MC缓释片药物释放

目的用人工神经网络模型定量的预测HPMC的量和其固有黏度对药物释放的影响。方法以难溶性药物别嘌醇为模型药物,固定其他因素,HPMC的量和HPMC的固有黏度作为自变量,设计了18个处方并进行释放度检查;其中的13个处方作为训练处方,其他5个处方为验证处方,将上述的变量作为人工神经的输入,以药物在各个取样时间点的释放为输出,采用剔除一点交叉验证法建立人工神经网络模型。通过线性回归和相似因子说明人工神经网络的预测能力。结果训练和验证处方人工神经网络预测值与实际测定相符。结论建立BP人工神经网络,根据HPMC的量和其固有黏度可以定量的预测药物在各个时间点的药物释放。     

Long-term safety of extended-release oxybutynin chloride in a community-dwelling population of participants with overactive bladder: A one-year study

In this multicenter, open-label study of extended- and immediate-release oxybutynin chloride, community-dwelling participants were studied for up to 12 months to evaluate the long-term safety profile of extended-release oxybutynin. Quality-of-life assessments designed to measure the impact of incontinence and evaluate treatment outcome were used to study subjective improvement.A total of 904 women and 163 men (mean age 64 years, range 29–91 years) were enrolled. The majority of discontinuations were in the first 3 months (25.5%); of those who continued after 3 months, 62% remained on extended-release oxybutynin chloride for one year. The majority of discontinuations were for adverse events; dry mouth was the most frequently cited event leading to discontinuation (8.4%). Significant improvements were seen in QOL measures. Long-term therapy with extended-release oxybutynin chloride was generally well tolerated and effective, improving quality of life significantly in participants with overactive bladder over 3–12 months of therapy.     

胃漂浮型缓释甲硝唑微囊的研制

以乙基纤维素和3号丙烯酸树脂为主要包囊材料。用液中干燥技术制备了甲硝唑微囊,并对不同制备条件下微囊的形态、释药率、漂浮能力及包封率进行了考察。以本法制得的微囊具有缓释性,能稳定漂浮于人工肠液中6h以上,8h累积释药率达90％,有较好重现性。     

Pharmacokinetic profile of a new fluoride preparation: Sustained-release monofluorophosphate

The pharmacokinetic profiles of a sustained-release monofluorophosphate (MFP-SR) preparation (76 mg) and of plain MFP (76 mg) were compared in six osteoporotic females. These studies were performed in a randomized, crossover, double-blind design to select a preparation that would result in therapeutic serum levels while avoiding high serum peak values. Following a single dose of 76 mg MFP-SR, the serum fluoride levels remained within the accepted therapeutic range (5–10 M/liter) for 24 hours. In contrast, following a single dose of 76 mg plain MFP, serum fluoride levels exhibited a wide circadian fluctuation and serum levels approximately threefold higher than those of the MFP-SR preparation (9.5±1.6 vs 3.5±0.8 M/liter, P<0.005). Compared with plain MFP, the sustained-release MFP had a significantly lower peak concentration (C_max MFP-SR: 10.6 ±3 vs C_maxMFP: 18.9±5 M/liter, P<0.005) and a significantly longer absorption lag time (T_maxMFP-SR 7.3±1.6 vs T_maxMFP: 3.0±0.6 h, P<0.05). Twenty-four-hour urinary fluoride excretion after ingestion of plain or SR fluoride was significantly increased from pretreatment values documenting absorption with either MFP formulation. Our results show that the use of sustained-release MFP preparation that we tested prevents the development of high peak levels associated with the use of plain MFP preparations. Furthermore, a single dose of MFP-SR resulted in serum fluoride levels within the accepted range of 5–10 M/liter for 24 hours.     

复方双嘧达莫缓释片的处方工艺及其对释放度的影响

目的:研究复方双嘧达莫缓释片的处方工艺及其对释放的影响.方法:以甲壳胺(CS)和海藻酸钠(AL)为辅料制备复方双嘧达莫缓释片,考察了制备工艺和辅料性质对骨架片释放度的影响,并建立高效液相色谱法测定复方双嘧达莫缓释片的含量测定方法.结果:复方双嘧达莫缓释片直接压片释放过缓;润湿剂对干颗粒的理化性质有影响.CS的用量和CS的脱乙酰度和对释放度影响显著;CS的密度、AL的粘度及AL的粒度对释放度有一定影响.结论:此处方缓释效果好,分析方法简便、灵敏、准确.     

载5-FU纳米微粒抗肿瘤的实验研究

目的： 研究抗癌药5-FU纳米控释静脉注射微粒的制备工艺及其体内外抗肿瘤作用。方法： 以聚乳酸 (PLA)作为基质材料，采用超声乳化-溶剂挥发法制备PLA包载5-FU的纳米微粒（5-FU-NPs）。扫描电镜观察5-FU-NPs形态，通过激光光散射实验测定5-FU-NPs的粒径分布。利用高效液相色谱(HPLC)测定5-FU-NPs的载药率，以MTT方法检测5-FU-NPs体外杀伤癌细胞效应，用5-FU-NPs不同剂量、给药频度条件下体内抑瘤实验。结果： 电镜观察5-FU-NPs为表面光滑的球形微粒，粒径分布平均值是191.1 nm，呈正态分布。5-FU-NPs载药率为15.2%。体外MTT实验提示5-FU-NPs作用明显优于5-FU（P<0.05）。体内抑瘤实验表明：5-FU-NPs间隔给药疗效优于未包载药物每日给药的疗效，量-效关系明显，且毒性减低。结论： 5-FU-NPs可以作为5-FU的有效载体，实现药物控制释放并减低毒性，发挥药物更佳的抗肿瘤作用。