BACKGROUND:Nicotine is a fat-soluble substance that is easily absorbed through the skin and mucosal tissues of the human body. However, its properties, such as light exposure, heat decomposition, and volatilization, restrict its development and application in external preparations.OBJECTIVE:This study focused on the preparation of stable nicotine-encapsulated ethosomes.METHODS:During their preparation, two water-phase miscible osmotic promoters, ethanol and propylene glycol (PG), were added to obtain a stable transdermal delivery system. Skin nicotine delivery was enhanced through the synergistic action of osmotic promoters and phosphatidylcholine in binary ethosomes. Various characteristics of the binary ethosomes were measured, including the vesicle size, particle size distribution, and zeta potential. In order to optimize the ratio of ethanol and PG, the skin permeability test was performed on mice in vitro in a Franz diffusion cell to compare cumulative skin permeabilities. The penetration depth and fluorescence intensity of rhodamine-B-entrapped vesicles in isolated mouse skin samples were observed using laser confocal scanning microscopy.RESULTS:When ethanol:PG was used in a ratio of 5:5 (w/w), binary ethosomes were found to be the most stable, had the highest encapsulation rate (86.13 ± 1.40), smallest particle size (106.0 ± 11.0) nm, maximum transdermal depth (180 μm), and maximum fluorescence intensity (160 AU). Nicotineencapsulated ethosomes (ethanol: PG = 5:5, w/w) were an efficient and stable transdermal delivery system.CONCLUSION:The nicotine-encapsulated ethosomes containing ethanol and PG are considered to be safe and reliable as a transdermal administration agent, which does not irritate the skin.

目的 在制备苦豆子总碱脂质体的过程中,加入两种水相混溶渗透促进剂:乙醇和丙二醇,以获得新的、稳定的透皮给药系统,增强苦豆子总碱(SATA)的皮肤传递.方法 注入法制备二元醇脂质体,并对其形态,大小,Zeta电位进行表征,包封率、囊泡稳定性和皮肤渗透特性为优化乙醇和丙二醇配比的重要考察因素,采用Franz扩散池对小鼠皮肤进行体外皮肤渗透实验,比较小鼠皮肤的累积渗透量.用激光共聚焦扫描电镜观察含有荧光素罗丹明B的苦豆子总碱二元醇脂质体在离体小鼠皮肤中的穿透深度及荧光强度.结果 当乙醇∶丙二醇=7∶3(w/w)时,二元醇脂质体的稳定性最好、包封率最高(89.13±0.42)％,粒径最小(103.00±16.15)nm,透皮深度(170 μm)最大和最强的荧光强度(MaxFI =160 AU).结论 制备的苦豆子总碱二元醇脂质体(乙醇∶丙二醇=7∶3,w/w)是一种高效且稳定的经皮传递载体.

Objective Nicotine diol liposome thermosensitive gels were prepared and the prescription was screened to optimize the drug transdermal transportation.Methods Poloxam 407（P407） and Poloxam 188（P188） were selected as the thermo sensitive materials, and nicotine-diol liposome thermo sensitive gels were prepared by cold solution method. The gelation temperature was used as the index. The formulation of nicotine diol liposome thermo sensitive gels were optimized by single factor experiment. The release properties of nicotine ethanol solution, diol liposome and thermosensitive gels containing P407/P188 diol liposome in vitro were investigated. Franz diffusion cell was used to compare the transdermal volume and intradermal retention of nicotine diol liposomes and diol liposomes gels.Results The thermosensitive gels were prepared in liquid state at room temperature and formed at 32 ℃. The release rate of diol liposome and diol liposome gels at 24 hours was（78.60%±0.43%） and（56.36%±0.26%）, respectively. Compared with diol liposome, diol liposome gels had obvious slow-release effect. 12 hours transdermal experiment showed that the diol liposome gel could increase the retention amount in skin, and the diol liposome could increase the transdermal depth.Conclusion Compared with diol liposomes, the thermosensitive gels of diol liposomes had a significant slow-release effect and significantly increased the intradermal retention of drugs.

目的:制备不同比例的乙醇与丙二醇的多奈哌齐醇脂质体,并比较皮肤渗透性及稳定性,优选出乙醇与丙二醇的最佳配比,使多奈哌齐的经皮转运更加优化.方法:对醇脂质体的形态、粒径、Zeta电位及包封率进行表征,通过Franz扩散池和共聚焦激光扫描电镜考察不同比例的乙醇与丙二醇制备的醇脂质体的皮肤渗透特性情况.结果:当乙醇:丙二醇为7:3(w/w)时,醇脂质体的稳定性最好、包封率最高(88.30±0.13)％,透皮深度(180μm)最大.结论:制备的多奈哌齐醇脂质体是一种高效且稳定的经皮传递载体.

目的 观察CXC趋化因子配体5(CXCL5)基因敲除小鼠与野生型小鼠抑郁样行为和血清炎症因子TNF-α、IL-1β、IL-6水平的差异.方法 取CXCL5+/-杂合子小鼠4只、C57野生型小鼠16只,雌雄各半.将CXCL5+/-杂合子小鼠雌雄配对进行繁殖,剪取子代鼠尾,提取基因组DNA,用qRT-PCR法鉴定子代小鼠的基因型,取CXCL5-/-纯合子小鼠继续繁殖,直至获得30只CXCL5-/-小鼠,其中雌性16只、雄性14只.取CXCL5-/-纯合子小鼠和野生型小鼠各8只,雌雄各半,称取4、6、8、10周龄小鼠的体质量;取10周龄CXCL5-/-纯合子小鼠和野生型小鼠各8只,以慢性不可预见性的温和刺激(CUMS)配合孤养来建立抑郁症模型,以小鼠出现自主活动明显减少为造模成功.采用强迫游泳实验和悬尾不动实验对小鼠进行抑郁症行为学评估;取小鼠腹主动脉血,检测血清TNF-α、IL-1β、IL-6水平.结果 雄性及雌性CXCL5-/-小鼠在4、6、8、10周龄时的体质量与同龄、同性别野生型小鼠比较,差异均无统计学意义(P均>0.05).与野生型抑郁症小鼠比较,CXCL5-/-抑郁症小鼠强迫游泳及悬尾不动时间均缩短,血清TNF-α、IL-1β、IL-6水平均降低(P均<0.05).结论 CXCL5基因敲除能够阻断小鼠的抑郁样行为,其机制可能与抑制炎症反应有关.

目的 分析抗精神病药物引起的药品不良反应(ADR)的发生特点,为临床合理用药提供依据.方法 收集2009年1月—2019年12月西安市精神卫生中心(以下简称"我院")在国家药品不良反应监测系统中上报的897例发生ADR患者的报表,其中775例发生了由抗精神病药物引起的ADR,将其ADR发生时间、临床表现、药品品种、累及系统或器官进行统计分析.结果 775例患者发生ADR共涉及16个药物品规,其中ADR发生率排在前10位的药品是奥氮平片、富马酸喹硫平片、氨磺必利片、氯氮平片、利培酮片、利培酮分散片、氟哌啶醇注射液、阿立哌唑口腔崩解片、盐酸齐拉西酮胶囊、盐酸齐拉西酮片.累及系统或器官以神经系统最多,共221例次(26.53％),其次是心血管系统,共202例次(24.25％).另外,用药后15 d内的发生ADR的患者占52.38％.结论 我院上报的抗精神病药物ADR的类型、比例与药品管理部门重点要求相一致,各个时期均可发生ADR,需要注意ADR发生率较高药物,尤其在用药后15 d内应注意监测并进行实验室检查.

目的 筛选抑郁症小鼠海马组织中差异表达的炎症因子基因,并进行生物信息学分析.方法 将12只C57小鼠分为对照组和抑郁症组,每组6只.抑郁症组通过慢性不可预知温和应激模型制备小鼠抑郁症模型,对照组不造模.取两组海马组织,采用实时定量PCR检测84个炎症因子基因.采用GeneSpring GX11.5.1软件分析基因芯片数据,获取两样本信号强度比值(Ratio),将Ratio>2或<0.5作为有表达差异,Volcano Plot筛选差异表达基因.对差异表达基因进行GO生物过程(GO-BP)富集分析和KEGG通路分析.通过对GO-BP分析及KEGG通路分析结果进行交集,筛选目标差异表达基因.结果 与对照组相比,抑郁症组中差异表达的细胞因子基因有6个,表达上调的3个基因分别为CXCL5、BMP2、IL10RA,表达下调的3个基因分别为CCL12、IL5、IL1A.差异表达基因主要参与白细胞迁移、白细胞趋化性及免疫系统过程等生物过程的调控,参与细胞因子与细胞因子受体相互作用通路、趋化因子信号转导通路及IL-17信号转导通路等.共筛选出4个目标差异基因,为CXCL5、BMP2、IL1A、CCL12基因.结论 抑郁症小鼠海马组织中差异表达的炎症因子基因主要为CXCL5、BMP2、IL1A、CCL12等,这些炎症因子基因可能通过调控多种生物过程和多条信号通路参与抑郁症的发病.

目的:研究臭椿生物碱canthin-6-one对小鼠的镇静催眠作用.方法:选昆明小鼠随机分为空白组、地西泮阳性药物组、canthin-6-one低、中、高给药组(5、10、20 mg·kg-1),采用阈上剂量和阈下剂量戊巴比妥钠诱导小鼠睡眠,记录入睡小鼠比例、睡眠潜伏期和睡眠持续时间.此外,酶联免疫法测定小鼠脑组织中5-HT、NE、DA和GABA含量.结果:中、高剂量canthin-6-one可使小鼠的站立次数和自主活动次数均明显减少(P＜0.05),可使阈上剂量戊巴比妥钠诱导的小鼠的睡眠潜伏期缩短(P＜0.05);各剂量组可使阈下剂量戊巴比妥钠诱导的小鼠入睡率提高(P＜0.05).此外,中、高剂量canthin-6-one也可降低小鼠脑组织中5-HT和NE含量,增加GABA含量(P＜0.05),对DA的含量有影响,但无统计学意义(P＞0.05).结论:Canthin-6-one有明显的协同戊巴比妥钠改善睡眠作用,其作用与相关神经递质(5-HT、NE、GABA)具有密切关系.

目的 研究北重楼(Paris verticillata)根中的化学成分.方法 利用正相硅胶柱色谱、中低压制备色谱仪、反相硅胶柱色谱、Sephadex LH-20凝胶柱色谱、制备高效液相色谱等分离方法从北重楼根部70％乙醇提取液的正丁醇萃取物中分离得到单体化合物,根据其理化性质及现代波谱技术鉴定其结构.结果 从北重楼中分离得到2个甾体皂苷和4个甾酮类化合物,分别鉴定为:偏诺皂苷元-3-O-α-L-吡喃鼠李糖基-(1→2)-[β-L-吡喃鼠李糖基-(1→4)]-β-D-吡喃葡萄糖苷(1)、重楼皂苷Ⅶ(2)、2-去氧甲壳甾酮(3)、5-hydroxyabutastorone(4)、2-deoxyintegristeroneA(5)、integristeroneA(6).结论 化合物4～6为首次从重楼属植物中分离.

目的:了解抗精神病药临床应用情况及发展趋势,为合理用药提供依据。方法:以限定日剂量(DDD)为指标,对本院2007～2009年抗精神病药的用药金额、用药频度进行分析。结果:3年来抗精神病药品种数稳定,消耗金额增长。平均年增长率为33%,抗精神病药占药品总金额的比例有逐年增长趋势。日用药金额逐年增长,年增长率达到15.5%。结论:临床使用的抗精神病药已经由传统的经典抗精神病药转向以利培酮、喹硫平、奥氮平、阿立哌唑、齐拉西酮、氯氮平为主的非典型抗精神病药。