热熔挤出技术制备泊沙康唑固体分散体及其体外评价

采用热熔挤出(HME)技术制备难溶性药物泊沙康唑(POS)固体分散体,提高其溶出度。利用溶解度参数、玻璃化转变温度和熔融法,初步筛选载体。进一步运用HME技术制备POS固体分散体,以溶出度为指标考察载体Kollidon VA64、Soluplus、Eudragit L100以及混合载体Kollidon VA64-Eudragit L100对药物的增溶能力。考察影响固体分散体溶出度的处方以及工艺因素、不同载体、挤出温度、增塑剂和载药量对溶出度的影响。采用差示扫描量热法(DSC)进行物相分析,并通过影响因素实验初步分析固体分散体的稳定性。结果显示以Kollindon VA64-Eudragit L100(2∶8)为载体,10%柠檬酸三乙酯为增塑剂,150 ℃挤出温度下制备的POS固体分散体,显著提高了POS的溶出度,DSC结果显示药物以无定形或分子形式存在于载体中。混合载体的比例、挤出温度、载药量以及增塑剂均能影响药物的溶出。固体分散体对湿度敏感,高温和强光条件下稳定。采用HME技术制备的固体分散体可以显著提高POS的溶出度。     

基于壳聚糖的丹参酮IIA固体分散体的研究

目的 将壳聚糖（CS）应用于丹参酮II_A（Tan II_A）固体分散体的制备,考察并比较以不同相对分子质量（M_W）的CS为载体的Tan II_A固体分散体的溶出度。方法 以CS为载体,采用溶剂法制备Tan II_A固体分散体,对不同M_W的CS以及药物与载体的不同比例所制备固体分散体的溶出行为进行比较研究,并进行物相分析。结果 Tan II_A-CS（M_W 3 000～5 000）按1∶9比例制备的固体分散体的体外溶出效果最好,60 min时药物的体外累积溶出率达到90%以上;经差示扫描量热（DSC）和扫描电镜（SEM）分析,固体分散体中药物以非晶形形式存在于载体中。结论 以CS为载体制备的Tan II_A固体分散体能显著改善Tan II_A的溶出;CS作为Tan II_A一种新型的固体分散体载体,具有实际应用价值。     

草胡椒素B固体分散体的制备及其性质研究

目的 将草胡椒素B（PB）制成固体分散体,改善PB的溶解度。方法 分别以聚乙烯吡咯烷酮（PVP）、聚乙二醇4000（PEG 4000）和泊洛沙姆188（F68）为载体,采用溶剂法或溶剂-熔融法制备PB固体分散体,并进行饱和溶解度和体外溶出度试验;利用差热分析（DSC）、电镜扫描（SEM）和红外光谱（IR）研究固体分散体的性质。结果 以PVP为载体制备的PB固体分散体的溶解度和体外溶出度优于PEG 4000和F68,且以PB-PVP质量比1∶6为最佳。结论 以PVP为载体制备固体分散体能显著增加PB的溶解度,且以过饱和的固态溶液或无定型状态均匀分布在载体中。     

CHMFL-KIT-110固体分散体制备、理化性质及大鼠体内药代动力学

分别以聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物（Soluplus）、泊洛沙姆407（Poloxamer 407）、聚乙二醇6000（PEG 6000）、共聚维酮（Kollidon VA64）为载体,十二烷基硫酸钠（SLS）、吐温80（Tween 80）、聚氧乙烯氢化蓖麻油（Cremophor RH40）为增溶剂,采用溶剂法制备难溶性药物CHMFL-KIT-110的固体分散体,以动力学溶解度和溶液过饱和现象为指标优化固体分散体的处方。通过傅里叶变换红外光谱法、差热分析法、X射线粉末衍射法对成品进行物相表征,并考察其初步稳定性及大鼠体内药代动力学行为。结果表明,当CHMFL-KIT-110、Soluplus和SLS质量比为1∶4∶0.5时,CHMFL-KIT-110动力学溶解度显著提高且无药物晶体析出。CHMFL-KIT-110以无定形状态分散于载体中,在加速条件下（40 ℃、75%相对湿度）敞口放置30 d未发生结晶现象。大鼠体内药代动力学表明,CHMFL-KIT-110固体分散体的c_max和AUC_0→t较原料药分别提高373.1倍和358.7倍。本研究为CHMFL-KIT-110的制剂开发和临床研究提供了理论基础。     

桂利嗪-聚乙烯吡咯烷酮固体分散体的研制

目的应用固体分散技术提高难溶性药物桂利嗪的溶解度和体外溶出速率。方法采用溶剂法制备桂利嗪-聚乙烯吡咯烷酮(polyvidone,PVPk30)固体分散体并测定其溶解度和体外溶出度。结果桂利嗪-PVPk30固体分散体的水中溶解度及体外溶出度均高于原药,且载体加入量越大,溶出速率越快;比例相同的固体分散体的溶出度明显高于其物理混合物。结论本实验所制备的桂利嗪-PVPk30固体分散体能加速体外溶出度和增大溶解度。     

多西他赛自乳化固体分散体的制备及体外特性研究

目的制备多西他赛自乳化固体分散体（DTX-SESD）,并考察其体外特性。方法以自乳化辅料和PEG6000为载体制备多西他赛固体分散体,进行溶解度、体外溶出度和稳定性实验,考察不同自乳化辅料、不同制备方法、不同介质对溶出度的影响。并采用差示扫描量热分析、X-射线粉末衍射分析以鉴别药物在载体中的存在状态。结果 DTX-SESD的溶解度和溶出度分别是原料药的约33.8倍和12.5（2 h）倍;自乳化辅料对药物溶出有显著影响;溶剂法和溶剂熔融法制备的自乳化固体分散体溶出度好于熔融法;溶出介质对溶出无显著影响;自乳化固体分散体中药物主要以分子状态存在。结论自乳化固体分散体能显著提高多西他赛的溶解度和溶出度。     

环孢素-PVP固体分散体的体外研究

目的 以聚维酮(PVP)为载体制备环孢素(CyA)固体分散体,并考察其体外溶出.方法 以溶剂法制备固体分散体,以X-射线衍射法鉴定CyA在体系中的存在状态,用红外光谱法检查药物与载体间是否具相互作用,以摇瓶法测定CyA在不同浓度十二烷基硫酸钠(SLS)中的溶解度,按《中国药典》2005年版溶出度第三法测定CyA从固体分散体中的溶出.结果 X-射线衍射图谱显示CyA结晶衍射峰消失,药物以无定形或分子状态存在于固体分散体中;红外光谱的结果表明,药物与PVP间无分子间作用力.药物从固体分散体中的溶出度比原药粉末显著提高,且随着PVP比例的增加而增大.结论 PVP能显著提高CyA的溶出度,可进一步用来制备CyA的固体剂型.     

热熔挤出技术制备小檗红碱固体分散体及其体外评价

[目的]采用热熔挤出技术制备微溶性药物小檗红碱的固体分散体,以提高其溶解度,延缓其体外释放行为。[方法]以Soluplus^® 为载体,采用同螺杆热熔挤出机制备小檗红碱固体分散体,通过差示扫描量热（DSC）分析、粉末X射线衍射（XRD）分析、扫描电子显微镜（SEM）观察和傅里叶变换红外光谱（FT-IR）分析对制备的固体分散体进行表征,并考察挤出物在不同介质中的溶解度和体外溶出度。[结果]DSC和XRD分析结果显示,固体分散体中小檗红碱的主要特征峰减弱甚至部分消失,SEM结果表明固体分散体为无规则形态。FT-IR结果表明小檗红碱与Soluplus^®之间可能存在氢键作用。所制备的小檗红碱固体分散体在pH 6.8的磷酸盐缓冲液中溶解度为原料药的2.59倍。体外溶出度结果显示,小檗红碱固体分散体具有明显缓释作用。[结论]成功制备了小檗红碱固体分散体,且能显著提高其溶解度,并延缓其体外释放行为。     

埃索美拉唑锌固体分散体的制备及其体外溶出特性

目的通过制备成固体分散体的方法提高埃索美拉唑锌的溶出度。方法以聚乙烯吡咯烷酮K30(PVPK30)和聚乙二醇6000(PEG 6000)为载体,采用溶剂法将埃索美拉唑锌制备成固体分散体,然后将所得固体分散体装填于肠溶胶囊,并考察其在人工肠液中的溶出特性;利用差示扫描量热分析(DSC)鉴别埃索美拉唑锌在固体分散体中的存在状态。结果随着载体比例增加,固体分散体体外溶出度先增大后减小;以PEG 6000为载体制备的固体分散体溶出度优于以PVPK30制备的固体分散体;DSC分析表明,埃索美拉唑锌在以PEG 6000为载体制备的固体分散体中以非晶型存在。结论固体分散体提高了埃索美拉唑锌的体外溶出速度。     

阿折地平固体分散体的制备及溶出度的考察

目的利用固体分散技术制备阿折地平固体分散体,并检测其体外溶出度。方法分别以聚乙二醇4000、聚乙二醇6000、泊洛沙姆188等为载体,用熔融法、溶剂法制备不同比例的阿折地平固体分散体。通过X射线粉末衍射法分析药物在固体分散体中的存在状态。采用紫外分光光度法测定阿折地平固体分散体的溶出度,根据测定结果筛选出两种方法制备的固体分散体进行压片,并比较阿折地平固体分散片的体外溶出特性。结果各种方法制备的阿折地平固体分散体均能加快药物溶出,且载体比例愈大,药物溶出越快。最优制备方法为以泊洛沙姆188为载体、药物与载体比例为1∶6,采用熔融法制备。结论采用固体分散技术可有效增加阿折地平的体外溶出度。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Development on Adjustable Calibration Marker for Shock Wave Focus

Shock wave lithotripsy （SWL） is a treatment of choice for upper urinary stones. However, this procedure is inappropriate for obese patients because the focus is often unable to reach the target owing to the limited focal distance in shock wave source. Although treating such patients in a blast path may increase the application length of shock wave source, it＇s difficult to find this path on the lithotripter monitor. For this reason, we invented an adjustable calibration marker in order to set an effective focus in the shock wave hath.     

Study on the TCM Pathogenesis of Angiopathic Complications of Type II Diabetes

Excess production of reactive oxygen species(ROS)of mitochondrion mediated by hyperglycemia is the common pathogenesis of angiopathic complications of diabetes.TCM holds that the damp from the dysfunction of spleen.kidney and liver is the causative factor of complications of diabetes.This is similar to the mechanism of Ros resulting in angiopathic complications of diabetes.When the angiopathic complications of type II diabetes mellitus(T2DM)are difierentiated as caused by turbid damp in TCM can be explained as ROS.Since the obstruction of pathogenic damp in channels and collaterals is said to be the main pathogenesis,the treating principle should be dissolving the damp to remove the obstruction.     

Leptin, Ghrelin and TNF-α before and after Hypo-caloric Traditional Chinese Diet and Auricular Acupuncture

INTRODUCTION Obesity is a complex emergent problem, which can be possibly solved not only by the diet but also by the life style and promotion of a constant physical exercise. 1, 2 No doubt careful attentions must be given to the nutritional condition of obese people, the dietary habits, the somatic build (i.e. distribution of fat mass) and the organic functions linked to formation of the fat mass. All the parameters should be constantly monitored before, during and after a diet treatment. 3, 4, 5     

Relationship between Dysglycemia and Carotid Atherosclerosis in Tibetan Population

People with dysglycemia are at high risk for atherosclerotic diseases. This study aims at investigating the atherosclerotic vascular damage in dysglycemia and its metabolic origin in Tibetan population.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

CLINICAL SIGNIFICANCE OF SERUM CYTOKINES IL-1β,sIL-2R,IL-6,TNF-α,AND IFN-v IN ACUTE CORONARY SYNDROME

Objectives To explore serum cytokines levels (including IL-1 β, sIL-2R, IL-6, TNF-α, and IFN-v) and their significance in patients with acute coronary syndrome (ACS) and the subsequent follow-ups, with attempt to estimate the role of various serum inflammatory markers in the diagnosis and assessment of ACS.Methods The study population include 40 patients with acute myocardial infarction (AMI), 40 patients with unstable angina pectoris (UAP), and 40 controls. Among the 80 patients, 60 patients attended a follow up 4 months later. Serum inflammatory markers including IL-1 β, sIL-2R, IL-6, TNF-α, and IFN-v were measured by enzyme linked immunosorbent assay.Results Serum IL- 1 β, sIL-2R, IL-6, TNF-α were significantly higher in AMI group or UAP group compared to the control group and became significantly lower 4 months later in the follow-up patients. Serum levels of IFN-v shows no significant difference between AMI group or UAP group and controls, also showing no significant change when measured in follow up patients. There was no correlation between serum creatine kinase-MB isoenzyme levels and serum inflammatory markers either in UAP or AMI group. Furthermore, when divided into two subgroups using Wagner's QRS scoring system in the AMI group, there is no difference of each serum inflammatory marker between ≤ 6 scores group and ＞ 6 scores group.Conclusion Serum levels of certain inflammatory markers may have some diagnostic value for ACS, and can be a useful marker reflecting disease stability.