CoQ10 Nanoparticles and Solid Lipid Nanoparticles Prepared by Supercritical Fluid Technology

CoQ10在药物、功能食品以及化妆品等领域用途广泛，但其制剂存在颗粒大、水溶性差、生物利用率低等问题。固体脂质纳米粒(SLN)是20世纪90年代发展起来的一种性能优异的新型纳米给药系统。SCF技术为一项新型的绿色技术，在许多领域中获得了重要的进展。本研究采用SCF技术制备CoQ10纳米粒以及CoQ10SLN。 应用RESS技术制备肉豆蔻酸纳米粒（如20MPa，60℃，60μm喷嘴对应产品的中值粒径230nm）和CoQ10纳米粒（如上述相同条件下得到的产品的中值粒径1.9m，索太尔粒径330nm）。研究表明，压力越高，肉豆蔻酸平均粒径越小，粒径分布越均匀；平均粒径随温度的升高而...CoQ10 as a lipid soluble compound has wide applications in pharmaceutical, food, and cosmetic industries. Yet, CoQ10 has some evident problems when it is used, such as relatively large particle size, insolubility in water, and low bioavailability. Solid lipid nanoparticles (SLN) represent a kind of nano-drug carrier with a lot of advantages. Over the past couple of years, important insights into t...学位：工学硕士院系专业：化学化工学院化学工程与生物工程系_化学工程学号：2062007115088

Preparation of Tripalmitin Micronization by Supercritical Fluids Technique

利用气体饱和溶液微粒形成技术实验装置,分别用超临界n2和超临界CO2制备三棕榈酸甘油酯微粒,探讨压力、温度以及喷嘴大小等工艺参数对微粒(粒径、粒径分布和形貌)的影响。结果表明:n2辅助过程得到的微粒基本为球状;预膨胀压力越高,粒径越小,粒径分布越窄;100μM喷嘴下制得的微粒粒径最小,且分布较均匀。CO2辅助过程得到的微粒部分为球状,部分为针状和片状;预膨胀压力越高,粒径越小,粒径分布越窄;喷嘴直径大小对微粒平均粒径及粒径分布影响不大;预膨胀温度升高,颗粒的粒径稍微增大。CO2辅助过程得到的微粒粒径比n2辅助过程得到的微粒粒径稍大,但两者的粒径分布相差不大。Generation of tripalmitin microparticles from its melts was investigated by using both supercritical CO2 and supercritical N2.The effects of various operating conditions,such as the pre-expansion pressure,pre-expansion temperature,and nozzle size on the particle morphology,particle size and particle size distribution(PSD) were investigated.Results showed that microspheres were obtained from the N2-assisted process,the particle size decreased and PSD narrowed with the increasing of the pre-expansion pressure,nozzle size showed no obvious effect on the microparticles,and pre-expansion temperature should be less than 72 ℃ to obtain solid particles.From the CO2-assited process,spherical,lamellate and needle-like particles were obtained,the particle size decreased,PSD narrowed with the increasing of the pre-expansion pressure,nozzle size showed no obvious effect on the particles and the pre-expansion temperature slightly increased the average size of particles.Particles' PSD from supercritical CO2 was close to that from supercritical N2

Composite microparticles of ibuprofen/lipid generated by supercritical fluids from their melts

采用CO2及N2辅助的气体饱和溶液微粒形成技术制备布洛芬/肉豆蔻酸、布洛芬/三棕榈酸甘油酯复合微粒,考察它们的形态、颗粒分布以及复合微粒中药物的溶出情况。N2辅助过程制得的布洛芬(质量分数5%)/肉豆蔻酸复合微粒与用该过程得到的纯肉豆蔻酸大小及粒径分布大致相同,而CO2辅助过程制得的布洛芬/肉豆蔻酸复合微粒却要比该过程得到的纯肉豆蔻酸的粒径要大,分布也较宽;CO2及N2辅助形成的布洛芬/肉豆蔻酸复合微粒无缓释效果。用N2辅助制备得到的含20%布洛芬(质量分数)的复合微粒保持了三棕榈酸甘油酯微粒化后的颗粒形貌,粒径更大;用CO2辅助制备得到的含20%布洛芬的复合微粒其粒径比三棕榈酸甘油酯微粒化后的颗粒粒径要小,粒径分布更窄;布洛芬/三棕榈酸甘油酯复合微粒具有缓释效果,而且用N2辅助制备的布洛芬含量为5%的复合微粒比布洛芬含量为20%的复合微粒溶出慢。Using the CO2-assisted and N2-assisted atomization processes,ibuprofen/lipid composite microparticles can be produced;the lipid includes myristic acid(MA) and tripalmitin(TP).The ibuprofen(5% in mass ratie)/MA composite microparticles show similar particle sizes to that of pure MA from the N2-assisted process,while the composite microparticles have a large particle size and particle size distribution,compared to that of pure MA from the CO2-assisted process.The dissolution reveals no controlled release of ibuprofen for the ibuprofen/MA composite microparticles either from the N2-assisted process or from the CO2-assisted process.For the ibuprofen/TP system,the obtained composite microparticles containing 20%(in mass) ibuprofen show similar particle morphology,while has a larger particle size(PS) than that of the pure myristic acid particles in the case of N2-assisted process.Nevertheless,the microparticles from the CO2-assisted process has a small PS and narrow PSD,compared to that of the pure myristic acid particles.The obtained ibuprofen/TP composite microparticles containing 5% or 20% ibuprofen show an evidently controlled drug release.For example,the drug release is only 20% in 500 min for the ibuprofen/TP microparticles containing 20% ibuprofen,prepared by the CO2-assisted process.国家自然科学基金资助项目(20406015);; 福建省新世纪优秀人才支持计划;; 福建省自然科学基金资助项目(2007J0167

Neural basis for successful encoding and retrieval of prospective memory

前瞻记忆是指对将来行为和事件的记忆,而相继记忆效应(Dm效应)是指根据记忆提取阶段的成绩,分析与之对应的编码阶段的项目和忘的项目之间的神经活动的差异.本研究采用任务转化范式,借助ERP仪器,使用汉字材料,探讨了前瞻记忆的Dm效应.研究发现,100～200ms(P150),250～280ms(fbN2),400～700ms(LPC)随后前瞻记忆击中的ERPs比随后前瞻记忆忘的ERPs更正.其中,早期的相继记忆效应(P150更正)可能反映了前瞻记忆将来意向的加工或者准备意的加工;而后两个时段与以往的研究结果一致,fbN2可能与汉语材料的加工有关,LPC则反映了记忆的精确编码.总之,本研究从ERP的角度提供了前瞻记忆编码与以往情景记忆编码有相同之处(LPC更正),又存在一些差异(P150更正)的证据,但这种差异需要进一步的研究来论证.</p

Effects of Low-Dose Exposure of Environmental Hormone Disruptors on Experimental Animals--- PCBs Congeners and Transgenerational Actions on Male Reproductive Toxicology

[[abstract]]多氯聯苯(PCBs)乃是一族相互類似的化合物，以二個相連的苯環為基本構造，依氯取代數目及位置的不同，PCBs共有209個可能的同類異構物。PCBs同類異構物中非鄰位的平面同類異構物，由於其結構與透過芳香烴受體誘發毒性之機轉與四氯戴奧辛類似，因此又被稱為類戴奧辛PCBs。單鄰位同類異構物對芳香烴受體的結合力較弱，而雙或多鄰位同類異構物呈非平面結構，無法與芳香烴受體結合，因而與平面同類異構物有極不相同的影響。我們過去的流行病學與動物實驗研究均發現，胎兒在子宮內暴露PCBs在成熟後會影響雄性生殖功能，然而為何胎兒在子宮內短暫接觸到此外來毒物，在多年後仍持續惡化？它是如何影響後代生殖健康目前仍不清楚。最近的研究發現環境毒性化學物質可能藉由改變生殖細胞的染色質或基因體外之DNA甲基化作用，將危害傳輸至下一代。雄性生殖細胞分化過程的基因體外資訊是一連串複雜的步驟，包括整體的重組與前減數分裂、減數分裂、與後減數分裂各時期的基因體外發生位置之改變。因此本三年期之計畫目標包括：一、評估胎兒在子宮內暴露不同PCBs同類異構物是否影響雄性第一子代(F1)的生殖功能；二、胎兒在子宮內暴露PCBs同類異構物是否會將此生殖功能變化傳輸到雄性第二子代(F2)；三、此代代傳輸的雄性生殖危害是否與生殖細胞的DNA甲基化改變有關？第一年計畫我們將探討胎兒發育過程暴露單鄰位PCBs 同類異構物 2,3’,4,4’,5-pentachlorobiphenyl (PCB 118) 與雙鄰位PCBs 同類異構物 2,2’,4,4’,5,5’-hexachlorobiphenyl ( PCB 153)；並比較PCB 118與PCB 153對日後成年時期之雄性生殖影響。懷孕Fisher大鼠在懷孕第8至第15天，每天以胃管餵食低劑量 PCB 118 (380 μg/kg)或PCB 153 (1900 μg/kg)，暴露劑量是參考台灣及其他工業化國家一般居民婦女乳汁PCB 118與PCB 153濃度的100倍而決定。F1於出生後第105天犧牲並進行精子數、活動力、游動速度、反應性氧化物質產生、睪丸造精過程DNA含量、組織學、凋亡相關基因與造精過程相關基因BC009436表現等分析。第二年計畫我們將設計大鼠交錯繁殖實驗探討子宮內之暴露是否藉由雄性生殖細胞的改變傳輸至F2。交錯繁殖設計組別包括：(一)、以控制組之雄性F1與控制組之雌性F1產生之雄性F2；(二)、以PCB暴露之雄性F1與PCB暴露之雌性F1產生之雄性F2；(三)、以PCB 暴露之雄性F1與控制組雌性產生之PCB暴露對外交錯繁殖雄性F2 (POC)；(四)、以 PCB 暴露之雌性F1 與控制組雄性產生之PCB 暴露反向對外交錯繁殖雄性F2 (RPOC)，並進行前述之生殖危害分析。第三年計畫我們將探討精子染色質DNA結構與精子整體DNA甲基化程度之關係，並以甲基化敏感限制酶，利用聚合酶鏈反應探討睪丸細胞與精子染色體特定片段之DNA甲基化之改變。相信此研究結果將在環境與職業衛生的領域，使我們更清楚了解PCBs如何改變生殖細胞，以及如何將此危害傳輸至子代的影響。[[abstract]]Polychlorinated biphenyls (PCBs) are a mixture of 209 possible congeners with different chlorine substitutions and they are potentially hazardous compounds in the environment for human beings. The group of dioxin-like PCBs with non-ortho coplanar congeners reveals toxic properties similar to those of 2,3,7,8-tetrachlorodibenzo-p-dioxin, and the mechanistic pathway for dioxins and dioxin-like PCBs is mediated through binding to aryl hydrocarbon receptor (AhR). The mono-ortho-substituted PCB congeners are less able to take a coplanar configuration yet can also bind to the cytosolic AhR, albeit with lower affinity. However, congeners with two or more ortho-chlorines, favor a noncoplanar conformation and do not bind to AhR that might exert distinct effects. We have investigated that exposure to PCBs and in utero can alter reproductive function in sexually mature men and rat offspring in adulthood. However, it is not clear why and how can the short-term exposure in utero last long-term adverse effects. Recent studies have shown that transgenerational effects of environmental toxicants require either a chromosomal or epigenetic alteration such as DNA methylation in the germ line. The setting of male-specific epigenetic information is a complex process, which involves a major global re-organisation, as well as localized changes of the nucleus structure during the pre-meiotic, meiotic and post-meiotic stages of the male germ cell differentiation. The specific objectives of this 3-year project are to evaluate whether (a) the effects of developmental exposure to various PCB congeners on male reproductive dysfunctions in male offspring or F1 generation; (b) the in urtero exposure of PCBs causes trangenerational adverse effects on male F2, and (c) the effects on reproduction correlate with altered DNA methylation in the germ line to multiple generations? In the project of first year, we will assess the effects of developmental exposure to mono-ortho PCB congener (2,3’,4,4’,5-pentachlorobiphenyl, PCB 118) and two-ortho PCB congener (2,2’,4,4’,5,5’-hexachlorobiphenyl, PCB 153) on adult male reproductive health. Fisher rat dams were treated by gavage on gestation day (GD) 8 to GD 15 with low dose of 380 μg PCB 118 or 1900 μg PCB 153/kg based on the 100-fold higher than the concentration in human milk reported from the general population in Taiwan and other industrial countries. F1 were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, testicular DNA content in spermatogenesis, histopathology, apoptosis-related and BC009436 gene expression will be assessed on postnatal day (PND) 105. In the project of second year, an outcross experiment was performed to determine whether the transgenerational phenotype is tranfmitted through the male germ line. F1 PCB-treated males were bred to F1 PCB-treated females to generate the F2 treated generation. F1 PCB-treated generation male outcross (POC) to control females, and F1 PCB-treated females reverse outcross (RPOC) to control males were analyzed for the reproductive assays as previously described. The project of third year will focus on measuring the relationships between sperm chromatin DNA structure and global sperm DNA methylation as well as methylation-sensitive restriction enzyme digestion analysis using a polymerase chain reaction (PCR)–based procedure to assess changes in DNA methylation patterns in testis on PND 6 and 105 and sperm samples from male offspring of F1, F2, POC, and RPOC on PND 105. The results will provide significant implications of understanding how PCBs reprogram the germ line and to promote a transgenerational disease for environmental and occupational health.[[note]]NSC97-2221-E327-009-MY

Evaluation of Therapeutic Effect of Atmospheric Low Temperature Nitrogen Plasma on Photoaging Rat Skin

目的评估大气压低温氮等离子体治疗大鼠光老化皮肤的疗效。方法采用健康雌性SD大鼠40只,随机分为2个大组:正常对照组(A组)和模型组(B组),其中模型组又分为3个小组,分别为等离子体低剂量治疗组(B1组)、等离子体高剂量治疗组(B2组)和自然恢复组(B3组)。共计4组,每组10只。除正常对照组(A组)外,B组均采用UVA+UVB紫外线灯同时照射,每日2 h,连续照射60 d,制备大鼠皮肤光老化模型。SD大鼠光老化制模成功后,给予自制大气压低温氮等离子体治疗。B1组采用0.1 W/mm~2等离子体低剂量治疗,连续治疗4次,每次间隔时间2周;B2组采用0.3 W/mm~2等离子体高剂量治疗,连续治疗2次,每次间隔时间4周;B3组无等离子体治疗,自然恢复。每次治疗后观察各组大鼠皮肤即刻反应及恢复情况,分别于治疗前和治疗后1个月活检取材,进行常规HE染色和Masson三色染色。观察治疗前后大鼠皮肤的大体变化和组织病理学变化,并用Image-Pro-Plus 6.0病理图文分析系统测定大鼠皮肤胶原蛋白含量变化。结果采用等离子体治疗组大鼠皮肤光老化大体变化和病理改变明显改善。B1组和B2组与B3组比较胶原含量明显增加,差异具有显著意义(P<0.05)。B1组和B2组两组组间比较,疗效无明显差异。结论等离子体对皮肤光老化有明显的治疗作用,具有术后恢复快、不良反应低等优点。Objective To evaluate the effect of atmospheric low temperature nitrogen plasma regeneration technique in treating photoagingrats.Methods An experimental study was performed on 40 female SD rats.All rats were randomly assigned to two primary groups:normal control group A and model group B.The model group B were further divided into 3 secondary sub-groups:low-energy treatment group B1,high-energy treatment group B2 and model control group B3.As a result,the 40 SD rates were eventually randomized 1:1:1:1 to the 4 groups(A,B1,B2 and B3) with 10 SD rats in each group.Except those inthe group A,the SD ratswere irradiated with UVA plus UVB for 2 hours per day to establish a skin photoagingmodel.After 60 days,the skin photoaging model was established.The atmospheric low temperature nitrogen plasmadevice was designed and set up.The rats in group Bl were given 4 treatments in total,once every 2 weeks with the energy set at 0.1 W/mm~2.In the meantime,The rats in group B2 underwent 2 treatments,once every 4 weeks with the energy set at 0.3 W/mm~2.After each treatment,the degree of downtimeand erythema were recorded.Full-thickness skin biopsy specimens were obtained from each group before the treatment and 30 days following the last treatment respectively.Clinical characteristicswere observed and histological analysis was performed usingroutine Hematoxilin-Eosin staining and Trichrome-Masson staining.The content of dermal collagen wasmeasured with Image Pro-Plus 6.0 software.Results Clinical and histological observation showed that both plasma treatment groups(B1 and B2) were significantly improved,and the collagen increasedremarkably compared to the model control group(B3),(P < 0.05).There was no difference between low-energy treatment group(B1) and high-energy treatment group(B2).Conclusions The atmospheric low temperature plasma regeneration technique is highly effective in treating photoaging skin with minimal down-time and few side effects.福建省教育厅科技项目(JB11049);; 泉州市科技计划项目(2012Z55重点项目

西安市PM_(2.5)和碳气溶胶质量浓度变化特征研究

为了探讨西安市PM_(2.5)和碳气溶胶质量浓度变化特征,从2012年3月~2013年2月对西安市大气 PM_(2.5)进行了为期一年的观测,并分析了有机碳(OC)和元素碳(EC)的质量浓度变化特征.结果显示,西安市2012年3月~2013年2月日均 PM_(2.5)质量浓度变化幅度为26.9 ~505.1 &mu;g/m~3, PM_(2.5)年平均质量浓度为114.0&plusmn;86.6 &mu;g/m~3,是中国PM_(2.5)空气质量标准(GB 3095-2012)年平均二级标准值(35 &mu;g/m~3)的3.3倍.PM_(2.5)季节变化特征为冬季 &gt; 秋季 &gt; 春季 &gt; 夏季.OC 和EC 年平均浓度值为21.44&plusmn;15.76 &mu;g/m~3和6.16&plusmn;3.38 &mu;g/m~3,OC/EC 年平均值为3.37&plusmn;0.95,变化范围为1.80~5.84,表明有二次有机碳气溶胶的存在.主成分分析法表明,西安市大气中的碳气溶胶主要来自汽油车和柴油车尾气、二次碳气溶胶以及生物质燃烧.</p