中药复方药物动力学方法学的国内研究进展

中药药物动力学研究是近十几年才迅速发展起来的药学新领域。中药药物动力学主要是研究中药单体、单方、复方在体内过程动态变化的规律，用数学方程式和药物参数来表达应用，指导中药新制剂的研究和临床合理用药。由于中药成分复杂，有效单体不明确，血药浓度低，检测方法欠缺，单体成分的药动学参数难以完整地表达中药复方药物的体内作用规律，中药复方药物药动学研究受到限制。中药复方药物药动学研究主要以在实验动物药物动力学水平上的单药和复方药物中的单一成分研究为主。中医药理论提倡整体观念，临床用药以复方为主，中药复方药物能体现中药配伍的整体性，发挥综合性作用，临床疗效好；因此，探讨中药复方药物的药动学规律已成为研究的热点。自1994年以来，研究提出各种假设和学说，如黄熙等提出“辨证药动学”新假说，新学说有时辰药动学、群体药动学、中药复方药动学、临床药动学等。     

定量构动关系及其在中药药效成分药动学研究中的应用与展望

在查阅国内外相关文献的基础上,初步讨论了定量构动关系研究与计算机辅助药物设计的相关关系,同时对其研究内容、研究方法以及影响其模型预测的因素进行了分析总结;着重论述了分子结构描述符的类型及其计算方法以及定量构动关系在中药活性成分药动学中的研究;对当前中药及其复方药动学的研究思路进行了简要概述,同时提出定量构动关系应用于中药复方药动学的研究思路,以期有助于推动中药的研究步伐。     

试论基于代谢组学与方证理论的药效学-药动学方法研究中药复方配伍规律

代谢组学的系统论方法与中医理论的整体观具有相似的属性。近年来,随着其迅速发展,代谢组学已应用于中医“证”及其模型的研究、中药及复方的作用机制研究、中药毒理研究等。研究内容侧重于“证”,关注内源性代谢组的应答(药效学与毒理学);较少涉及“方”,即方剂本身及其动态变化过程(药动学)。而“辨证论治,方证对应”正是中医理论的精髓。为此,从“方证对应”的角度,浅析应用代谢组学研究中药复方配伍规律的方法,希望借此对中医药理论现代研究提供参考。     

黄翁异功戊己汤治疗慢性溃疡性结肠炎48例

目的：观察应用中药黄翁异功戊己汤治疗慢性溃疡性结肠炎48例的临床疗效及药物副反应情况。方法：对于48例慢性溃疡性结肠炎应用黄翁异功戊己汤治疗2个疗程（2周为1疗程,休息1周再用药）,休息1月后检查评定疗效;并设对照组48例用中药补脾益肠丸（广州白云山制药公司药）治疗观察。结果：黄翁异功戊己汤治疗慢性溃疡性结肠炎48例治疗总有效率为95.8%;对照组用补脾益肠丸治疗48例总有效率为75.0%,有明显的差异。结论：应用黄翁异功戊己汤治疗慢性溃疡性结肠炎临床疗效好,症状消失明显,复发率低,属纯中药制剂无任何毒副反应,值得临床推广应用。     

我们提出的方剂药动学假说(Ⅰ)：内涵及其创新点

从１９９１年至今,我们提出并发展了中药复方药动学研究的思路,包括证治药动学假说其六要素、方剂血清成分说翅民分概念、脾主ＰＫ假说和方剂治疗药物监测设想等。本文介绍了上述思路及其创新点。     

中药药物代谢动力学研究概况

药物代谢动力学(Pharmacokinetics)是从20世纪70年代初发展的研究体内药物动态规律的一门科学。其研究方法已在新药设计,优选给药方案,改进药物剂量,提供高效、长效、低毒、低副作用的药剂等方面发挥了重要作用。随着中药现代化进程的日益推进,运用中药药物代谢动力学的理论研究中药和中药复方作用机制、设计及优选给药方案,促进其新药开发、剂型改良及标准化已经成为研究热点。但因中药及其复方成分复杂,药理作用的多样性,让中药的药动学研究较通常的化学药物更为困难。综观近些年的文献资料,本文试对中药药物代谢动力学的研究概况作一综述。     

中药(复方)药动学研究现状及研究方法探讨

根据目前中(西)药药动学研究的方法,分析中药学科的特点,结合生物数学知识及多年单成分药动学研究工作,分析了中药药动学研究现状及亟待解决的问题,提出了中药多成分体系药动学研究新方法——总量统计矩法,该法既能满足中医宏观要求(宏观量化可算)又能满足现代科学微观可测(可按目前单个成分药动学方法进行研究)的要求。适应中医药理论要求的新的中药(复方)药动学研究方法可以在目前单个成分(指标)的药动学研究方法的基础上建立和发展。     

我国药物动力学研究50年发展概述

首先回顾了该学科的世界发展,分析了这门较年轻的学科的基本理论和基本方法在临床治疗学、临床药理学、实验药理学、分子药理学、生物学、生物化学和毒理学等多个医学领域的应用,在药物设计、药物制剂、药品质量控制等药物研究开发中的重要作用。回顾了国内的发展历程,列举了国内学者的一些药物动力学著作和论文在该学科概念、原理、方法和应用等方面的贡献。中草药药代动力学的研究为药物动力学提出了新的课题。中药特别是中药方剂十分复杂,其药动学的研究较通常的化学药物的药动学更为困难,因此其研究起步较晚,但发展十分迅速。20世纪80年代以来,该领域的研究十分活跃,新理论、新方法的涌现使中草药药动学迈向了一个新的高度。其发展大致经历了3个发展阶段：第一阶段（1949--1970年）主要进行活性成分的体内过程研究,第二阶段（1970--1990年）中药的药代学得到了迅速发展,第三阶段,1990年以来,一门新的中药药动学正在形成。近几年来．国内代谢组学的研究引起了极大的重视,也获得了可喜的发展。在分析中药药代动力学的难点和热点的基础上,认为应用代谢组学方法和技术能为解决复杂体系的中药研究产生一定的推动作用。     

超高效/高分离度快速/超快速液相色谱在中药及其制剂研究中的应用

超高效液相色谱(UPLC)、高分离度快速液相色谱(RRLC)和超快速液相色谱(UFLC)是近几年来推出的一种新的液相色谱技术,峰容量、分析效率、灵敏度和分辨率较常规HPLC有了很大的提高。其主要用于中药成分分析、中药指纹图谱、中药及其复方定量测定。此外,与TOF-MS、MS/MS联用还可用于中药代谢产物、中药复方血清化学成分和药动学等复杂体系的生物分析,以及药物的研究与开发,是复杂体系中药分离分析的重要手段。着重就其在中药及其复方研究中的应用进行介绍。     

我国药物动力学研究50年发展概述

首先回顾了该学科的世界发展，分析了这门较年轻的学科的基本理论和基本方法在临床治疗学、临床药理学、实验药理学、分子药理学、生物学、生物化学和毒理学等多个医学领域的应用，在药物设计、药物制剂、药品质量控制等药物研究开发中的重要作用。回顾了国内的发展历程，列举了国内学者的一些药物动力学著作和论文在该学科概念、原理、方法和应用等方面的贡献。中草药药代动力学的研究为药物动力学提出了新的课题。中药特别是中药方剂十分复杂，其药动学的研究较通常的化学药物的药动学更为困难，因此其研究起步较晚，但发展十分迅速。20世纪80年代以来，该领域的研究十分活跃，新理论、新方法的涌现使中草药药动学迈向了一个新的高度。其发展大致经历了3个发展阶段：第一阶段（1949--1970年）主要进行活性成分的体内过程研究，第二阶段（1970--1990年）中药的药代学得到了迅速发展，第三阶段，1990年以来，一门新的中药药动学正在形成。近几年来．国内代谢组学的研究引起了极大的重视，也获得了可喜的发展。在分析中药药代动力学的难点和热点的基础上，认为应用代谢组学方法和技术能为解决复杂体系的中药研究产生一定的推动作用。     

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.     

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.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.