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目的以壳聚糖为酶触型结肠靶向给药系统的材料,研制可用于结肠靶向的多单元口服给药系统(迷你片),以期为结肠部位疾病治疗的药物输送提供重要参考。方法以结肠癌的治疗药物-吲哚美辛为模型药物,首先制备固体分散体,再采用直接压片法和包衣技术制备尤特奇-壳聚糖双层包衣结肠靶向迷你片,考察靶向迷你片在不同释放介质中的释药行为,采用小动物活体荧光成像技术考察制剂在体内的转运和吸收情况,并以比格犬为动物模型进行药动学研究和生物利用度评价。结果制备的壳聚糖多单元结肠靶向迷你片可以完整形态通过大鼠胃和小肠,并靶向在结肠部位缓慢释放,比格犬体内药动学数据表明,自制结肠靶向迷你片的释药时间显著延长,血药浓度平稳。结论本实验制备尤特奇-壳聚糖双层包衣多单元迷你片给药系统具有较好的结肠靶向性和缓释效果,可为治疗结肠疾病的制剂开发提供重要参考。     

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??OBJECTIVE To study the chemical constituents of Whole Plants of Patrinia villosa (Thunb.) Juss. METHODS Compounds were isolated by a combination of various chromatographic techniques including column chromatography over macroporous resin, Sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by physiochemical properties and spectral analysis. RESULTS Nine compounds were isolated and identified as (E,4R)-4-hydroxy-4,5,5-trimethyl-3-(3-oxobut-1-enyl)cyclohex-2-enone (1), vomifoliol (2), cis-4-hydroxymellein (3), dehydrovomifoliol (4), 3R,5S,6R,7E,9S-3,5,6,9-tetrahydroxy-7-megastigmane (5), loliolide (6), 4-methoxybenzyl alcohol (7), sphenanthin A (8), and urea (9). CONCLUSION Compounds 1-7 are isolated from Patrinia genus for the first time.     

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??OBJECTIVE To investigate the chemical constituents from the whole plants of Lagopsis supina. METHODS The compounds were isolated and purified by various column chromatography, and their structures were identified based on their physiochemical properties and spectroscopic data. RESULTS Thirteen compounds were isolated from the n-hexane, dichloromethane, and water extracts of the whole plants of Lagopsis supina by using various chromatographic methods. Their structures were identified as phytol(1), daucosterol(2), 8-O-acetylharpagide(3), antirrinoside(4), ajugoside(5), ajugol(6), harpagide(7), 1-O-caffeoyl-??-D-glucopyranose(8), 1-O-coumaroyl-??-D-glucopyranose(9), 2-hydroxy-5-(2-hydroxyethyl)phenyl-1-O-??-D-glucopyranoside(10), methyl 2-O-??-D-glucopyranosylbenzoate(11), adenosine(12), and sucrose(13), respectively. CONCLUSION Compounds 1 and 3-13 are isolated from the plants of Lagopsis genus for the first time.     

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??OBJECTIVE To investigate the stability of etanercept in vacuum and water to lay foundation for study on its bioactiveprotection. METHODS Umbrella sampling and steered molecular dynamics simulation aqueous solution adopted to study the dissociation process of dimer etanercept with Gromacs software and amber99sb-ildn force field. RESULTS Potential of mean forcel(PMF) free energy of etanercept dissociation in vacuum was approximately three times of that in aqueous solution. And the maximum barrier force of etanercept dissociation in vacuum was approximately ten times of that in aqueous solution. The solvation environment had effect on the stability of antibody protein. Freeze-drying in vacuum could improve the stability of antibody protein. CONCLUSION In the process of steered molecular dynamics simulation, the pulling force can be got easily and is less affected by other factors, which can be used to characterize the stability of active structure of antibody protein dimer.     

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??OBJECTIVE To investigate the chemical constituents of the seeds of Lepidium apetalum Willd. METHODS The compounds were isolated and purified by Diaion HP-20, Toyopearl HW-40, MCI Gel CHP-20, ODS, silica gel chromatography combined with Pre-HPLC and the structures were identified on the basis of spectral data and physiochemical properties. RESULTS Sixteen compounds were isolated and identified from the water extract as catechol(1), protocatechuic aldehyde(2), 2-phenyl acetamide(3), methyl- 5-hydroxypyridine-2-carboxlate(4), benzylcarbamic acid(5), N-benzylacetamide(6), raphanuside C(7), 1-phenyl-1,2-ethanediol(8), 2-(4-hydroxyphenyl)-ethanol(9), isorhamnetin-7-O-??-L-rhamnopyranoside(10), kaempferol(11), methyl 2,4,6-trihydroxybenzoate(12), 2-(4-hydroxyphenyl)acetonitrile(13), syringic acid(14), protocatechuic acid(15), and methyl sinapate(16). CONCLUSION Compounds 1-16 are isolated from this plant for the first time.     

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??Anthracyclines generally possess antitumor activities and they are clinically broad-spectrum anticancer antibiotics. But some of them have prominent toxicities and drug resistances. These limit their further development and applications. However, proper structural modifications can sometimes solve these problems. So lots of new anthacyclines are obtained through total-synthesis or partial-synthesis for the purpose of finding more effective new drugs. In this paper, combing with our previous work and referring the literatures, we briefly introduce the mechanism, drug resistance, cardiac toxicity of anthracycline, and mainly review the structure-activity relationships of ring A, sugar moieties and twin drugs of anthracyclines. These can provide powerful evidence for further developments of new anthracyclines.     

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??Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, the skin barrier function limits the transdermal penetration of macromolecular drugs.Microneedle arrays can remarkably increase the skin permeability for drugs, especially macromolecular drugs, by forming microchannels in the skin. In recent years, the types and usages of microneedle have made great progress. This review focuses on remarking the wound repair and pharmacology evaluation, as well as introduces the microneedle percutaneous drug delivery system.     

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??OBJECTIVE To analyze the connotation and composition of the clinical value of drugs, and to build the index system for the evaluation of drug's clinical value, hence to provide references for its scientific evaluation. METHODS We designed the preliminary constructs index system referencingmedicine clinical evaluation indicatorsof German and French firstly. And then the expert interview and Delphi survey were used to analysis to determine the index system and index weight of medicine clinical evaluation. RESULTS The classified index system of the clinical value was established, which was composed of 2 first-grade indexes including clinical value and innovation value and 15 grade two indexes. Experts were invited to assess the value ranking according to the background information of rosuvastatin, atorvastatin and simvastatin statin drugs by their generic names. The expert's scoring results were summarized to determine the sequence. And it were compared with the average market prices in Germany, France, Britain, the United States, South Korea, Japan and analyzed. CONCLUSION The clinical value of drugs is an international standard for determining the reasonable price of drugs. This research method is feasible to determine the drug prices sequencing by the classified clinical value of drugs in the same kind of product. The price sequencing of some generic names of statin drugs did not correspond with its clinical value sequence, and the price can not reflect its value. The integrity and authenticity of the background data directly determine the classification of the clinical value. Various parties are needed to participate in providing detailed data and information.     

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??OBJECTIVE To investigate the protective effects of aidi injection on cisplatin (CDDP)-induced acute nephrotoxicity in rats. METHODS Forty male Sprague-Dawley rats were randomly divided into 5 groups, including the control group, CDDP group, the low, medium and high dose Aidi injection group (5, 10, 15 mL??kg^-1). Except the rats in control group, the rats of other groups were injected with CDDP on the third day. Aidi injection groups were administered to the rats once daily for 7 consecutive days. The control and CDDP groups were given corresponding regime of saline. On the eighth day, determine the content of serum creatinine (Scr) and blood urea nitrogen (BUN) in the rat, detect the level of superoxide dismutase (SOD), glutathione reductase (GSH-Px) and malondialdehyde (MDA) in the kidney tissue; observe HE staining slices of rats and find the renal pathological changes. RESULTS Compared with control group, the levels of Scr, BUN and MDA content were increased significantly in CDDP group, whereas the contents of SOD and GSH-Px were decreased significantly. There were serious, renal tubular epithelial cell apoptosis and inflammation in the kidney tissue. Kidney histopathology indicated that Aidi injection alleviated CDDP-induced tissue damage. The levels of Scr, BUN were decreased significantly in the low dose Aidi injection group, whereas the activity of SOD and GSH-Px were increased significantly. The medium dose of Aidi injection could increase the level of SOD and GSH-Px. The high dose of Aidi injection could enhance the activity of GSH-Px, without statistically significant effect on other indicators. CONCLUSION The RESULTS indicate that the low and middle dose of Aidi injection might protect the renal tissue from nephrotoxicity induced by cisplatin through anti-oxidation.     

穿心莲内酯体外稳定性研究

目的：考察穿心莲内酯在体外的稳定性，为制剂研究提供有效的参考。方法：将穿心莲内酯原料药分别溶解于不同pH值的磷酸盐缓冲液中，采用经典恒温法，用反相高效液相色谱法测定穿心莲内酯的含量，并在此基础上考察该药37℃时在不同生物样品中的稳定性和该药在不同有机溶剂中的稳定性。结果：穿心莲内酯在不同pH值条件下稳定性不同，以pH3-5最为稳定；而生物样品中，在小牛血清最稳定，小鼠肺匀浆中次之。结论：穿心莲内酯在不同条件下其稳定性不同，该结果为穿心莲内酯及其相关制剂的研究提供一定的参考。     

返魂草颗粒中2种成分在大鼠血浆中的药代动力学行为

目的建立LC-MS法同时测定返魂草颗粒中对羟基苯甲酸和对羟基苯乙酸在大鼠血浆中的含有量,并研究两者的药代动力学行为。方法分析采用C18色谱柱(4.6 mm×150 mm,5μm),流动相为0.1%乙酸-乙腈;体积流量0.6 m L/min;进样量10μL。测定大鼠灌胃给药后不同时间点的血浆药物浓度,并计算两种成分的药代动力学参数。结果对羟基苯甲酸和对羟基苯乙酸线性范围分别为0.4~2 000、5~2 000 ng/m L,平均回收率分别为98.36%、96.67%,RSD小于4.91%;基质效应分别为89.82%、95.94%,RSD小于7.78%,无交叉干扰,RSD小于15%。两者药动学参数分别为t1/2(9.769±2.766)、(4.983±1.003)h,T_(max)(1.083±0.204)、(0.583±0.204)h,C_(max)(122.9±46.225)、(1 273.5±316.491)ng/m L,AUC_(0-t)(853.95±242.035)、(3 066.109±524.633)μg/(L·h),CL/F(1 223.792±389.327)、(333.049±53.07)L/(h·kg),MRT_(0-t)(12.602±3.475)、(5.225±0.688)h。结论该方法快速、精确、可靠,适用于返魂草颗粒的药代动力学研究。     

穿心莲内酯醇提工艺研究

目的：考察影响穿心莲中主要有效成分穿心莲内酯的提取因素。方法以提取液中醇浸膏收率及穿心莲内酯为检测指标,考察乙醇回流提取时提取次数、溶剂倍量及所用乙醇浓度对其含量的影响,并通过正交试验确定最佳提取工艺。结果提取的最佳工艺用95％乙醇提取3次,第一次用10倍量提取1．5h、后两次用7倍量分别提取1h。结论所用工艺稳定可行。     

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??OBJECTIVE To establish a method for determination of the total content of andrographolide sulfonate, transport of two kinds of main components in the injection in Calu-3 and Caco-2 cell model, can be applied to the assessment of lung and oral administration to the safety and effectiveness of drugs. METHODS Screening of safe concentration of drugs by cytotoxicity test. Injection of andrographolide total sulfonate in safe concentrationwere applied to Calu-3 and Caco-2 cell models. Samples were taken for a certain period of time to determine the influence of concentration and time on the transport, and the apparent osmotic coefficients of the principal components were calculated. RESULTS When the concentration of the drug was less than 500 ??g??mL^-1, the survival rate of Calu-3 and Caco-2 cells was close to 100%.The established cell model showed excellent compactness and integrity.In the Calu-3 cell model, the apparent permeability coefficients of andrographolide sulfate C and 9-dehydro-17-hydro-andrographolide were 1??10^-5 orders of magnitude.In the Caco-2 cell model, both were 1??10^-6 orders of magnitude.On two cell models, the efflux ratios were less than 2. CONCLUSION The principal component of andrographolide total sulfonate injection is not the substrate for P glycoproteins, it has moderate absorption in the intestine, and has good absorption in the respiratory tract. Pulmonary administration is safer and more effective.     

菊葛天麻颗粒质量标准研究

目的:建立菊葛天麻颗粒的质量标准.方法:采用薄层色谱进行定性鉴别;采用高效液相色谱法测定方中葛根素含量.结果:确立了制剂中葛根、菊花、当归、天麻的鉴别方法,通过方法学系统考察和样品含量测定,建立了本制剂中葛根素的含量测定方法,测得3批样品中葛根素的质量分数为8.10,7.72,8.74mg·g-1,其葛根素的线性范围为19.95 ～ 159.6 μg,回归方程y=224 765.8X+ 79 379.77(r=1.000).平均回收率为97.50％,RSD 1.45％.结论:本实验建立的鉴别和含量测定方法简便、准确、重复性好,适用于本品质量的控制.     

高效液相色谱法测定穿心莲内酯掩味树脂复合物的含量

目的:建立HPLC法测定穿心莲内酯树脂复合物中穿心莲内酯含量的方法。方法:HypersilC₁₈柱,以甲醇-水(55∶45)为流动相,检测波长225nm。结果:穿心莲内酯进样量在(0.0956～0.956)μg范围内线性关系良好,回归方程为Y=230.4X+47.264,r=0.9994(n=6),平均加样回收率为99.99%(n=9),RSD为0.88%。结论:该方法准确、可靠、重复性好,可作为穿心莲内酯树脂复合物中穿心莲内酯的含量测定方法。     

升压灵注射液药代动力学研究

目的测定升压灵注射液在家兔体内药代动力学参数.方法采用高效液相色谱法,以升压灵注射液中辛弗林为指标进行测定.流动相为甲醇-水(5545,内含0.02M磷酸和0.2%十二烷基硫酸钠),色谱柱YWG18(4.6×150mm),紫外检测波长为275nm,柱温40℃,流速1ml/min.结果升压灵注射液静注后在兔体内呈二室模型分布,其药代动力学参数是Vc=53.81ml/kg,K12=0.27/min,K21=0.13/min,K10=0.6/min,T1/2α=0.76min,T1/2β=8.23min,α=0.92min,β=8.42×10-2/min,AUC=276.36μg/L·min,Cl=32.05ml/min.结论临床上使用升压灵注射液时,可短期多次或缓慢静脉滴注给药.     

绿原酸的药代动力学研究

采用高效液相色谱法,测定绿原酸的体内药代动力学参数。     

地黄寡糖的吸收动力学研究

目的：研究地黄寡糖在小鼠及大鼠体内的吸收和吸收部位。方法：用高效液相色谱／柱后荧光衍生化法测定小鼠口服和静脉注射水苏糖后的血药浓度；大鼠原位肠灌流模型研究水苏糖的吸收和吸收部位；肠抑菌实验室观察水苏糖在肠道内的代谢。结果：口服吸收快但很少?生物利用度为３．８２％，在胃、十二指肠、空肠和回收的吸收率分别为６．０３％、１３．８０％、８．３３％和０．５３％，在大肠内不吸收，正常组及卡那霉素抑菌组的小鼠灌     

Pharmacokinetic and Pharmacodynamic Interaction of Boswellic Acids and Andrographolide with Glyburide in Diabetic Rats: Including Its PK/PD Modeling

The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin‐induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as C_max, AUC_0–n, AUC_total, t_1/2, and mean residence time, and decreased the clearance, Vd, markedly as compared with the control group. In rat liver, microsomes BA and AD have shown CYP3A4 inhibitory activity significantly (p < 0.01), compared with the vehicle group. The increase in hypoglycemic action by concomitant administration of glyburide with BA or AD was more in diabetic rats than when the drugs were used singly and with the control group, which suggests the enhancement of glucose reduction capacity of glyburide in diabetic rats along with BA or AD. In PK/PD modeling of BA and AD with glyburide, the predicted PK and PD parameters are in line with the observed PK and PD parameters. The results revealed that BA and AD led to the PK/PD changes because of glyburide‐increased bioavailability and because of the inhibition of CYP3A4 enzyme. In conclusion, add‐on preparations containing BA or AD may increase the bioavailability of glyburide, and hence the dose should be monitored. Copyright © 2016 John Wiley & Sons, Ltd.