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??OBJECTIVE To explore the effects of Dracocephalum total flavonoids(TFDM) on myocardial ischemia/reperfusion injury(MIRI)induced autophagy in rat. METHODS In vivo MIRI model was established with ischemia 30 min and reperfusion 120 min, by ligation of left anterior descending coronary artery. TFDM(30 mg??kg^-1??d^-1) and autophagy activator(1 mg??kg^-1??d^-1) or inhibitor(25 mg??kg^-1??d^-1) pretreatment was given before making the model. The MIRI-induced infarct size, the activities of lactate dehydrogenase(LDH), creatine kinase isoenzyme(CK-MB) in plasma and apoptosis protein caspase-3 in tissue and the expression level of autophagy-related proteins LC3, Beclin-1 were observed. RESULTS Compared with model group, the experiment revealed that autophagy inhibitor alleviated MIRI-induced myocardial damage by decreasing the infarct size, myocardial enzyme LDH and CK-MB leak; and reducing apoptosis protein caspase-3 activity level. In addition, TFDM pretreatment significantly inhibited the expression of autophagy-related proteins LC3 and Beclin-1. CONCLUSION TFDM shows inhibitory effects on MIRI-induced autophagy,which may play an important role in the protection against MIRI.     

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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 analyze the mechanism of clinical hold in USA and to provide reference and enlightenment for clinical trial review process reform in China. METHODS Analyzed the regulation, review process, reasons and impacts of drug clinical hold in USA and compared with clinical trial system in China, then provided advice for our country. RESULTS AND CONCLUSION FDA review IND by implied license process within only 30 d, and may permit the clinical trials begin as early as possible, the clinical trial could be imposed on hold, and the hold could also be lifted or transfer into inactive status, thus protect the health and rights of subjects to the largest extent, and in the same time improved the review efficiency. It is necessary and feasible that clinical hold is introduced into clinical trial system in our country.     

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??OBJECTIVE To establish a detection method based on a novel type of two-dimensional liquid chromatographic system (2D-LC-UV) for determination of paraquat in poisoned patients' urine, and assess the methodology and characteristics of the two-dimensional chromatography. METHODS 2D-LC-UV contains 1st and 2nd liquid chromatography and FLC transferor. Urine sample of 100 ??L was directly injected without pretreatments, and paraquat was on-line concentrated and primarily separated on the 1^st Aston SX1 column, then trapped on Aston SX column and separated by Aston SX1 column. The mobile phase of the 1st liquid chromatography, trapping column and 2nd liquid chromatography were acetonitrile-2 mol??L^-1 ammonium acetate binary solution(1:10, V:V, 1.0 mL??min^-1), pure water and 2.5 mol??L^-1 ammonium acetate solution-methanol-acetonitrile ternary system (5:3:1, V:V:V, 1.0 mL??min^-1), respectively. The column temperature was maitained at 40 ??, and the UV adsorption wave length was set at 285 nm. RESULTS The chromatographic system was capable of processing 500 ??L urine. Paraquat was transferred and separated completely in the two-dimensional system with linear calibration curve over the concentration range of 20-20 000 ng??mL^-1 (r=0.999 9). The urine matrixes from different samples had little interference effect. The chromatographic balance time was less than 15 min, and the calibration curve was stable for more than 90 d. CONCLUSION Because of its accuracy, stability, automation, and independence of specialized technical personnel, the established chromatographic method is ideal for quick test of paraquat in poisoned patients, providing scientific basis for clinical treatment of patients with paraquat poisoning.     

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??OBJECTIVE To summarize the pharmacoeconomic studies of adalimumab in the management of Rheumatoid Arthritis, discuss the cost-effectiveness and adverse reaction of combination use of adalimumab and DMARDs, and compare the economic values of TNF-?? inhibitors.METHODS Search Pubmed and MedLINE for pharmacoeconomics studies of adalimumab using in the treatment of RA. All the results are systematically summarized and assessed. RESULTS Seven studies on pharmacoeconomics assessment of adalimumab were selected and discussed. Compared with conventional DMARDs, adalimumab costs more but obviously extends the QALYs of RA patients. Adalimumab also provides significant improvement in symptom severity with less adverse reaction. The efficacy of combination use of adalimumab and MTX is better than adalimumab alone. In terms of cost and effectiveness, adalimumab has advantages over infliximab and is equal to etanercept.CONCLUSION Though adalimumab costs higher for the RA patients, it can significantly improve the quality of life when in the combination treatment with DMARDs, as well as reduce adverse reactions. Compared with other TNF-?? inhibitors, adalimumab shows superiority both in efficacy and cost. Thus, adalimumab is recommended for RA patients that don??t respond to DMARDs.     

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??OBJECTIVE To prepare ropivacaine ethosomal gel and study its transdermal permeation. METHODS The ropivacaine ethosomes were prepared by ethanol injection method. The formulation and the preparation method of ethosomes were optimized by orthogonal experiment. The particle size, morphology and encapsulation efficiency were evaluated,and the carbomer was added as the base for the preparation of the ethosomal gel. The penetration experiments of ropivacaine ethosomal gel through mouse skin were performed by Franz's cell. The cumulative penetration amount was calculated. RESULTS The obtained ethosomes were approximately spherical, the size were (127.6??4.8) nm. The entrapment efficiency of ropivacaine in ethosomes was (77.58??1.07)%. Accumulative permeation amount of ropivacaine ethosomal gel within 24 h was 73.07 ??g??cm^-2, which was about 1.56 times of normal gel. CONCLUSION The gel is feasible in preparation technique, controllable in quality and can significantly promote transdermal penetration of ropivacaine.     

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??OBJECTIVE To study the chemical constituents from the tubers of Hemsleya penxianensis. METHODS The constituents were isolated from the tubers of H. penxianensis and purified by column chromatography, and the structures were identified by spectral analysis and chemical methods. RESULTS Five compounds were isolated from the tubers of H. penxianensis and the structures were identified as 2??,3??,16??,20, 24-pentahydroxycucurbita-5, 25(E)-diene-11,22-dione(1), cucurbitacin ??a(2), cucurbitacin ??_b(3), hemslecins G(4), and jinfushanencins B(5). CONCLUSION Compound 1 is a new compound.     

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??OBJECTIVE To study the pharmacokinetics of hot-melt spray-dried andrographolide granules and compare it with andrographolide bulk drug. METHODS A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the concentration of andrographolide in plasma of rats which were respectively given micronized andrographolide and hot-melt spray-dried andrographolide granules, then the pharmacokinetic parameters were calculated. RESULTS The pharmacokinetic parameters of andrographolide after a single dose administration of micronized andrographolide and hot-melt andrographolide were as following: t_1/2 were (347.33??9.32) and (390.82??8.78) min, t_max were (30.00??5.94) and (60.00??3.48) min, ??_max were (1 940.14??21.21) and (1 818.22??23.64) ng??mL^-1, AUC_0-t were (427 515.71??37 350.03) and (426 406.31??20 577.75) ng??min??mL^-1, AUC_0-inf were (545 423.14??47 969.18) and (593 569.87??30 247.35) ng??min??mL^-1, Vz/F were (43.48??4.75) and (44.96??3.81) kg??L^-1, CL/F were (86.78??3.35) and (79.74??2.89) kg??L^-1??min^-1, respectively. CONCLUSION Compared with the bulk drug, the hot-melt spray-dried andrographolide granules have a longer t_1/2, lower ??_max and delayed t_max in rats.     

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??OBJECTIVE To design and synthesize series of quercetin derivatives by introducing allyl or prenyl groups and investigate their antitumor activities in vitro.METHODS Compounds 2, 3, 4, 5, 6, 7 and 8 were synthesized with quercetin as starting material through the etherification reaction.The antitumor activities were evaluated by MTT assay against human lung cells (A549), human breast cancer cells (MDA-MB-231), and human hepatoma cells (HepG2).RESULTS Two allyl-substituted and five prenyl-substituted quercetin derivatives were synthesized. Compounds 4, 5, 6, 7, and 8 were new compounds, and their structures were characterized by ¹H-NMR and ¹³C-NMR. Compounds 6 and 7 exhibited observable anti-proliferative activity. Compound 6 inhibited the growth of A549, MDA-MB-231, and HepG2 cells with IC₅₀ values of 15.23, 16.56, and 12.32 ??mol??L^-1, respectively.Compound 7 restrained the growth of A549 and MDA-MB-231 cells with IC₅₀ values of 8.92 and 2.90 ??mol??L^-1, respectively. CONCLUSION Compounds 6 and 7 synthesized by introducing prenyl groups into quercetin have significant anti-tumor activities, which are worth of further research.     

我国川贝母的质量分析

 目的 通过对2013年72批川贝母药材及饮片全国抽验情况,总结我国川贝母的质量问题,并探讨聚合酶链式反应-限制性内切酶长度多态性方法在检验中应注意的问题。方法 参照《中国药典》2010年版一部标准方法,对所抽取的样品进行检验和研究,发现并探讨其质量问题和检测方法。结果 抽验结果表明,市场上川贝母的不合格率为25.4%,聚合酶链式反应-限制性内切酶长度多态性方法在检验中对取样环节应予以明确规定。结论 应进一步完善和提高标准,加强质量监管,并建立专项抽验的长效机制,保证中药材及饮片的质量和安全。     

基于ITS2序列鉴定川贝母及其混伪品基原植物

本研究对川贝母5种不同基原植物ITS2序列进行PCR扩增和测序;同时扩大研究范围,从GenBank上下载川贝母及其常见混伪品共10个物种13个样本的ITS2序列。用MEGA4.1计算其种间、种内的K-2-P距离,并分析各样本间ITS2序列二级结构的差异,最后利用ITS2序列重构其系统发育树。结果显示川贝母基原植物种内最大K-2-P距离为0.0276,与混伪品的种间最小K-2-P距离为0.0583;川贝母及其混伪品的ITS2二级结构存在明显差异;重构的系统发育树显示川贝母不同基原物种聚为一支,能较好与混伪品区分。研究结果表明ITS2条形码序列能够成功鉴定川贝母及其混伪品的原植物,为川贝母混伪鉴别提供了新工具。     

川贝母组织培养的研究

川贝母再生鳞茎在一定激素组合的ＭＳ培养基上．可不经低温直接产生愈伤组织并进一步分化成小植株。组织培养物的总生物碱含量是原种及市售川贝的２～４倍。培养与原种鳞茎的游离全蛋白图谱完全一致。     

中药川贝母资源学与商品鉴别研究进展

中药川贝母是我国传统名贵珍稀中药材,具有很高的药用价值和保健功效,开发潜力巨大,市场前景广阔。通过对近年来中药川贝母的资源分布、生物学特性、品质生态学特性、引种栽培、商品鉴别等研究进行全面分析整理,编制川贝母基原植物分类检索表及市售混伪品鉴别检索表,为中药川贝母资源调查、保育栽培、质量控制和评价及相关混伪品的鉴别工作提供了依据,也为中药川贝母种质资源持续利用,规模化引种栽培,野生抚育,濒危保护,新资源开发,新品种选育等方面提供了资料。今后,应进一步加强对川贝母野生种质资源的保护及其生物学特性相关研究,加强川贝母品种选育与生产技术的集约化系统化研究,从更深层次更广范围更高水平推动中药川贝母的发展。     

基于ATR-FTIR成像技术的川贝母粉末显微光谱鉴定

目的:建立一种简便快速的贝母粉末鉴定方法,以准确区分川贝母与其他贝母粉末,保证川贝母粉末的真实性。方法:使用ATR-FTIR成像技术直接测量贝母粉末的显微红外光谱,通过主成分分析和归一化相对峰强度法对测量结果进行定性和定量解析,寻找川贝母与其他贝母粉末的显微红外光谱差异特征。结果:不同品种贝母粉末的显微红外光谱图像中均存在三类主要像素,分别具有淀粉粒、蛋白质和细胞壁的特征吸收信号,而川贝母粉末中主要对应于淀粉粒的第一类像素数量最多。以1200~900 cm~(-1)区域吸收峰面积为目标峰,以1700~1500 cm~(-1)区域吸收峰面积为参比峰,计算像素平均归一化相对峰强度Rm值。川贝母粉末的Rm值稳定在0.70左右,显著高于其他贝母粉末,可以作为区分川贝母和其他贝母粉末的量化指标。结论:使用ATR-FTIR成像技术,可以建立简便快速、客观量化的贝母粉末显微光谱鉴定方法。     

川贝母的资源学研究进展

概述了川贝母的来源分布、鉴定、生态学、栽培方面的研究进展,介绍了近年来发展起来的鉴定技术、与川贝母品质相关生态因子的研究及其在人工栽培中的应用,提出了存在的主要问题及今后研究的方向。     

川贝母转录组中SSR位点信息分析

目的:通过分析川贝母转录组简单重复序列标记(SSR)信息,为其分子标记辅助育种及种质资源保护提供技术支撑。方法:采用Illumina Hi Seq2000技术平台对川贝母鳞茎及叶片进行高通量测序,采用MISA对Unigene进行SSR位点分析。结果:从转录组得到44 973条,Unigene中共检测到3 817个SSR位点,分布于3 367条Unigene序列中,出现频率为8.49%,平均每10.37 kb序列出现1个SSR位点。其中重复类型最多的为三核苷酸和二核苷酸,所占比分别为56.51%和27.06%。三核苷酸重复基序CCG/CGG所占比率最大,其次为二核苷酸重复基序AG/CT。6种SSR重复类型的重复次数主要集中于4~12次,24.55%SSR的序列长度20 bp。结论:川贝母SSR位点出现频率较高,类型丰富,多态性较高,为其遗传多样性分析和遗传图谱构建及分子辅助育种提供了丰富的候选分子标记。     

聚合酶链式反应-限制性片段长度多态性方法对太白贝母鉴别检验的适用性探讨

目的：探讨聚合酶链式反应-限制性片段长度多态性方法（PCR-RFLP）对于太白贝母的适用性。方法：采集太白贝母野生及栽培品,收集市场上太白贝母伪品,利用性状、PCR-RFLP鉴别法、DNA序列分析三种方法分析太白贝母与常见伪品的区别。结果：从性状上看,太白贝母栽培品与伪品往往非常相似,较难辨别;通过PCR-RFLP方法可以正确、客观的鉴别太白贝母与常见伪品,基于ITS2 的DNA条形码方法进一步验证了PCR-RFLP法的准确性。市场上太白贝母的伪品多为伊犁贝母。结论：PCR-RFLP鉴别法可准确鉴别太白贝母与其伪品;市场上太白贝母伪品较多,应加强监管。     

基于传统性状客观化分析的川贝母质量评价

目的对川贝母的外观性状进行客观量化,完善其质量评价方法。方法用游标卡尺测定高度和直径,在人眼对外观色泽观察的基础上用色差仪对粉末色泽进行客观量化,通过紫外分光光度法测定总生物碱的含量,对高度、直径、△E值与总生物碱含量测定结果进行统计学分析,确定外观性状与内在成分之间的相关程度。结果高度与总生物碱的含量呈极显著负相关(P <0. 01)、直径与总生物碱的含量呈负相关,综合来看随着川贝母鳞茎的增大,总生物碱含量呈降低趋势。△E值与总生物碱含量之间的相关性不显著。结论由于总生物碱含量可以客观地反映川贝母的质量,本实验的结果为川贝母传统以"个小为佳"、"碎贝、破贝不可入药"的观点赋予了科学的依据,肯定了川贝母"不得水洗"的传统加工方法。不同规格的川贝母中以松贝为优。     

中药川贝母定量分析方法研究

目的:研究常用中药川贝母的定量分析方法。方法:应用高效液相色谱法。以4种川贝母共有的有效成分贝母辛为指标;采用AgilentHypersilBDS C₁₈(4. 0mm×2 5 0mm ,5 μm)色谱柱,以乙腈水 二乙胺(37∶6 3∶0 .0 3)为流动相,流速1 0mL·min^-1;Alltech 2 0 0 0蒸发光散射检测器检测,外标两点法定量。结果:贝母辛在0 . 0 3188～1. 0 2 0mg·mL^-1呈线性,回收率为10 2. 1% (n=5 ) ,RSD 3. 86 %。根据33批不同产地或来源的川贝母药材中贝母辛的含量结果,确定贝母辛的含量限度为0 . 0 0 70 %。结论:本法为良好的贝母辛的定量分析方法,可用于川贝母药材的质量控制。