基于网络药理学和分子对接技术探讨中药黄芩治疗黑色素瘤的作用机制.利用中药系统药理学数据库和分析平台筛选黄芩的有效成分,利用GeneCards、OMIM、PharmGkb等数据库查找与黑色素瘤有关的靶基因.应用Cytoscape3.7.1软件建立中药-成分-靶点-疾病网络结构图,借助STRING数据库平台构建蛋白质相互作用网络.从黄芩中筛选到36个有效成分,其中22个为核心有效成分,包括黄芩素、汉黄芩素、刺槐素等;与黑色素瘤相关的靶基因有37个,其中13个为核心基因,包括CCD1、AR、IL-6等.GO分析结果显示,黄芩主要参与DNA结合转录激活活性、RNA激活酶Ⅱ特异性等;KEGG分析结果显示,黄芩的37个靶基因富集了癌症信号、细胞凋亡信号通路、p53信号通路等.采用分子对接技术将核心成分黄芩素与其作用的7个核心基因进行分子对接,发现黄芩素与这些靶点之间均具有良好的对接活性.利用皮肤黑素瘤A375细胞模型进行体外实验,结果也证实黄芩素可能是黄芩实现抗黑色素瘤作用的主要活性成分.

肠道和皮肤具有多种相似之处,两者均定植有大量菌群.其中,肠道菌群对机体健康具有重要影响.肠道菌群的紊乱可能引发炎症反应,进而导致组织损伤或自身免疫反应.大量研究表明,肠道菌群与皮肤健康密切相关,并据此提出"肠-皮肤轴"理论.该文探讨了肠道菌群对银屑病、特应性皮炎、寻常性痤疮这3种常见炎症性皮肤病的影响,展望了肠道菌群在炎症性皮肤病治疗中的重要作用.

Objective:To evaluate the systemic absorption and safety of multiple doses of topical tazarotene/betamethasone dipropionate cream in healthy subjects and patients with psoriasis.Methods:From September 2008 to April 2009, 12 healthy subjects collected from Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly and equally divided into tazarotene 0.15%/betamethasone dipropionate 0.15% cream group and tazarotene 0.2%/betamethasone dipropionate 0.2% cream group; these subjects were instructed to apply 0.03 g of the test drug per day on each of the 4 body sites, including the flexor aspects of bilateral forearms, waist and back, for 7 consecutive days, and venous blood samples were obtained before, and 1, 3, 5 and 7 days after the start of drug application. From October 2010 to August 2011, 60 patients with non-cephalic psoriasis collected from the Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly divided into 3 groups at a ratio of 3∶1∶1, i.e., tazarotene 0.05%/betamethasone dipropionate 0.05% cream group ( n = 36) and tazarotene 0.05% gel group ( n = 12) topically treated with a cream vehicle in the morning and the test drug at night, and betamethasone dipropionate 0.05% cream group ( n = 12) topically treated with the test drug twice a day (once in the morning and again in the evening) ; the treatment lasted 6 consecutive weeks, and venous blood samples were collected before, and 2, 4 and 6 weeks after drug application. Liquid chromatography-tandem mass spectrometry was performed to determine the concentrations of tazarotenic acid and betamethasone in plasma. During the trial, adverse events in the subjects were recorded, routine blood and urine examinations were carried out, and liver and kidney function were evaluated before and after treatment. Results:The plasma concentrations of tazarotenic acid and betamethasone in the 12 healthy subjects were below the lower limit of quantitation (0.04 μg/L) after 1-, 3-, 5- and 7-day treatment. After the consecutive treatment, tazarotenic acid and betamethasone were detected in 2 (5.56%) and 4 (11.11%) patients respectively at week 2, 4 or 6 in the tazarotene 0.05%/betamethasone dipropionate 0.05% cream group, and the highest plasma concentrations of tazarotenic acid and betamethasone were 0.112 and 0.201 μg/L respectively; in the betamethasone dipropionate 0.05% cream group, betamethasone was detected in 2 of 12 patients, and the highest plasma concentration of betamethasone was 0.112 μg/L. No test drug-related systemic adverse reactions or laboratory abnormalities were observed in any of the healthy subjects or patients.Conclusion:Multiple doses of topical tazarotene/betamethasone dipropionate cream has advantages of little systemic absorption, no long-term accumulation and good systemic safety.

皮肤外用制剂要求在皮肤局部发挥药效,口服给药药物的生物利用度研究方法对于皮肤外用制剂并不适用.目前血管收缩测定法已被FDA认可,但该法只适用于糖皮质激素类药物,其他外用制剂仍需通过临床对比试验来评价其生物等效性.FDA仍在努力寻找其他的研究方法,如胶带粘贴法、皮肤微透析法、开流微量灌注及体外研究方法.本文对以上方法的研究进展进行综述.

竹篮、背篓、簸箕……只要在恩施境内的乡下走一趟,这些篾织品随处可见,能编织日用品的篾匠师傅也比比皆是.这些大山深处的恩施乡民的生活,与传统的竹篾编织息息相关.但在巴东县清太坪镇二里坡村五组有这样一位传奇的竹篾编织老艺人,他能将各种书画编到竹器上,笔画勾勒到竹篾间需要周密的设计,用掩盖式的编织方法将已经相当精致的竹丝用绣花针多次分割,通过高温对竹丝进行染色,然后再来编织,其作品堪称一绝.他就是民间艺术大师吕启文.

目的:考察醋酸曲安奈德微透析探针体外回收率的影响因素,探索提高微透析探针回收率的方法.方法:采用高效液相色谱法考察温度、灌流液流速、探针类型以及灌流液成分(羟丙基-β-环糊精、脂肪乳、牛血清白蛋白)对醋酸曲安奈德体外回收率的影响.结果:醋酸曲安耐德探针回收率随温度增高而增加;随灌流液流速增加而降低;不同类型的探针对醋酸曲安耐德回收率不同;灌流液成分会对醋酸曲安奈德回收率产生较大影响.结论:采用PBS(pH 7.4)溶液添加1％或2％牛血清白蛋白为灌流液,醋酸曲安奈德体外探针回收率得到较大提高,且回收率和传递率相等.

Cutaneous microdialysis is a unique technique for in vivo examination of unbound drug concentrations in dermis and subcutaneous tissues.Whenever the dermis is the target tissue of topical treatment,dermal microdialysis (DMD) is the first choice for acquisition of real-time kinetic data.It has unique advantages for the research on topical drug penetration into skin with impaired barrier or lesions.In the past decades,this technique has developed quickly and proved to be a widely applicable,safe,and efficient tool for dermatopharmacokinetic and pharmacodynamic research into topical drugs.However,further research is warranted to evaluate the reproducibility of microdialysis as well as the exact relationship between probe insertion and tissue damage,and to make this technique more applicable to studies into liposoluble drugs.

Objective To determine the intracutaneous concentration of Ftibamzone given percutaneously to test animals and investigate its percutaneous penetrability and the intracutaneous drug level.Methods An HPLC method combined with homogeneization was used to determine the intracutaneous concentration of Ftibamzone after topical administration.Results The percutaneous absorption and penetrability of Ftibamzone was relatively low.Conclusion The results of the test can give reference to the study of dermatopharmacokinetics of Ftibamzone in human.

Objective To evaluated the influence of multi-drug resistance gene 1(MDR1) C3435T,G2677T/ A and C1236T polymorphism on the pharmacokinetics of isotretinoin in 21 heathy male subjects.Methods Blood samples were collected from 21 healthy male subjects who received a single oral dose of 40 mg isotretinoin.The genotypes of MDR1 C3435T,G2677T/A and C1236T of the samples were detected by allele-specific amplification(ASA-PCR).The pharmacokinetic parameters of isotretonoin were compared between the different genotypes of MDR1 by statistical comparisons method.High performance liquid chromatography-electrospray ionization mass spectrometry(HPLC-MS) was used for the quantification of isotretinoin in human plasma which was standardized by dosage and body weight.Pharmacokinetic parameters were determined by non-compartmental analysis.Results For C1236T,the Cmax,Tmax,AUC 0-60 of carriers with CT and TT was remarkably higher than those with CC(P=0.057,P=0.252,P =0.049,respectively),the T1/2 and MRT of carriers with CT and TT was remarkably lower than those with CC(P=0.011 and P=0.035).For G2677T/A,there was no significant pharmacokinetic parameters difference among the different genetype subgroups(P0.05).For C3435T,there was no significant pharmacokinetic parameters differences among different genetype subgroups(P0.05).In addition,the Tmax of carriers with CC and CT was higher than those with TT(P=0.03).Conclusion It suggests that the MDR1 C1236T polymorphism influenced the human absorption of oral isotretinoin.Although there is genetic linage diequilibrium between C3435T and G2677T/A which can influences the isotretinoin absorption,the genetic polymorphisms of MDR1 C3435T and G2677T/ A had no effect to isotretinoin pharmacokinetic parameters in this research.

AIM To investigate the bioequivalence of two compound chlorzoxazone tablets in healthy volunteers.METHODS Single oral doses of two compound chlorzoxazone tablets(chlorzoxazone 250 mg and paracetamol 300 mg) were given to 20 healthy male volunteers in an open,randomized and crossover study. The plasma concentrations of chlorzoxazone and paracetamol were determined by HPLC-MS method with glipizide and acetophenetidin employed as the internal standard,and the pharmacokinetic parameters were calculated with BAPP2.2.RESULTS The major pharmacokinetic parameters of test and reference tablets in the singledose study were as follows;for paracetamol,ρ_(max) were(5.1±1.5) vs.(5.2±1.7) mg·L~(-1);t_(max) were(0.6±0.4) vs.(0.6±0.4) h;t_(1/2)were(3.0±0.4) vs.(3.0±0.5) h;AUC_(0-12)were(16.4±4.7) vs.(17.0±5.5) mg·h·L~(-1);AUC_(0-∞) were(17.6±5.1) vs.(18.2±6.0) mg·h·L~(-1),respectively.In the case of chlorzoxazone,ρ_(max) were(7.0±1.3) vs.(7.0±1.3) mgΛL~(-1);t_(max)were(0.9±0.6) vs.(1.0±0.5) h;t_(1/2) were(0.9±0.1) vs. (0.9±0.1) h,AUC_(0-∞)were(16.6±3.5) vs.(17.0±4.1) mg·h·L~(-1),AUC_90-∞) were(16.7±3.5) vs.(17.0±4.1) mg ? h ? L~(-1),respectively.There were no significant differences in pharmacokinetic parameters between two compound chlorzoxazone tablets(P0.05).The relative bioavalibility of paracetamol and chlorzoxazone in compound chlorzoxazone tablets were(99.3±14.3)%and(99.5±14.8)%,respectively.CONCLUSION The test tablet is bioequivalent to the reference tablet for chlorzoxazone and paracetamol in healthy volunteers.

目的 建立高效液相色谱-质谱联用法测定血浆中辛伐他汀浓度的方法,经方法学验证其灵敏度、专属性、线性范围、精密度、准确度、稳定性和介质效应等.方法 20名男性健康受试者分两组进行单剂量二交叉试验,测定天津药业焦作有限公司研制的辛伐他汀片相对于杭州默沙东制药有限公司生产的辛伐他汀片的生物利用度.单剂量口服辛伐他汀试验片 (10 mg/片,4片) 及辛伐他汀参比片(20 mg/片,2片)后,测定辛伐他汀的血药浓度经时过程,并计算试验制剂和参比制剂的主要药代动力学参数.结果 Cmax分别为(6.2±2.8)ng/mL和(6.0±2.6)ng/mL,Tmax分别为(1.8±0.6)h 和(1.8±0.5)h,t1/2分别为(3.4±1.1)h和(3.2±1.1)h,MRT分别为(5.2±1.2)h和(5.3±1.3)h,AUC0-14分别为(21.6±8.8)(ng·h)/ml和(21.6±8.9)(ng·h)/ml,AUC0-14分别为(23.4±9.0)(ng·h)/ml和(23.3±8.9)(ng·h)/ml;按AUC0-14计算,试验制剂中辛伐他汀片的相对生物利用度为(100.5±10.4)%;AUC和Cmax经对数转换后方差分析检验,Tmax经Wilcoxon符号秩检验,表明差异均无统计学意义.结论 将AUC和Cmax对数转换后经双单侧t-检验表明,试验制剂和参比制剂生物等效.

Objective To compare the bio-availability between test gliclazide sustained release tablet and commercially available reference tablet.Methods A HPLC/MS method was developed and used to determine gliclazide plasma concentrations of 20 healthy volunteers in an open randomized two-way crossover test after single oral dose and multiple oral doses.The pharmacokinetic parameters were estimated.Results After single oral gliclazide sustainde release tablets of reference (30mg) or test (30mg) drugs were given,gliclazide plasma concentration against time was calculated and evaluated.The main pharmacokinetic parameters after a single oral dose of test versus reference drug were as follows: Cmax was 1.21±0.26 vs 1.09±0.24μg/ml,Tmax was 7.4±1.8 vs 7.0±1.6h,AUC0～72 was 26.23±8.65 vs 25.88±8.87μg·h·ml-1,respectively,AUC0~∞ was 27.65±9.80 vs 27.12±9.90μg·h·ml-1. The Cmax,Cmin,Cav,Tmax,DF,AUCss of gliclazide test versus reference tablets after multiple oral doses were 1.37±0.49 vs 1.31±0.41μg/ml;0.069±0.075 vs 0.060±0.066μg/ml;0.41±0.20 vs 0.42± 0.19μg/ml;6.0±1.7 vs 6.6±2.6h;3.46±0.99 vs 3.29±1.06;29.66±14.10 vs 29.95±13.40μg·h ·ml-1 respectively.The AUC and AUCss were tested after natural logarithmic transformation and no difference with statistical significance was found.Conclusions The test formulation is bioequivalent to the reference formulation for gliclazide.

AIM: To establish a HPLC-UV method for the study of pharmacokinetics and bioavailability of baicalin in human plasma. METHODS: The study was performed with 18 male volunteers according to a random 2-way cross-over design. Plasma samples of 18 male volunteers after oral administration of 750 mg baicalin test capsules and reference tablets were prepared by solid phase extraction and the concentrations of baicalin were determined by HPLC-UV method. Pharmacokinetic parameters were also estimated. RESULTS: The main pharmacokinetic parameters of baicalin test capsules and reference tablets were as follows: c_(max)(91±s 33)μg·L~(-1) and (86±29) μg·L~(-1), t_(max)(7.4±1.3) h and (7.4±1.0) h, AUC_(0-24)(586±233) μg·h·L~(-1) and(579±(173) μg·)h·L~(-1), AUC_(0-∞)(616±249) μg·h·L~(-1) and(613±180)μg·h·L~(-1), respectively. The relative bioavailability of baicalin test capsules was(101±(18) %). CONCLUSION: The HPLC-UV is proved to be simple, sensitive and rapid method showing the bio-( )equivalence of the two formulations.