Immunopotentiating effect of freeze-drying Natto powder on mice

以小鼠为实验对象,分别以75、150、300Mg.kg-13个剂量组的纳豆冻干粉给予小鼠灌胃30天后,进行小鼠细胞免疫指标(脏器/体重指数、迟发型变态反应(dTH)和体液免疫指标(抗体生成细胞、血清溶血素)的测定。研究结果发现,各剂量组的各项检测结果与空白对照组比,纳豆冻干粉对小鼠体重、脏器重量影响不明显,但能够促进小鼠迟发型变态反应;提高小鼠抗体生成细胞数和血清溶血素水平,且当剂量达到150Mg.kg-1以上时,具有明显的提高免疫力的作用。本项研究表明纳豆冻干粉具有增强小鼠细胞及体液免疫功能的作用。To study the effect of freeze-drying natto powder on the mice immune system.The mice were feed with freeze-drying natto powder at the dose of 75,150 and 300mg·kg-1.respectively,once a day for 30 days.Index of organs/body,delay allergy(DTH),the number of the antibody-producing cells and the blood-serum erythrocytolysin were measured to judge the effect of freeze-drying natto powder on the immune system.All the examination results of the experimental group in comparison with the control group showed that there was no significant effect on the mice body weight,but the DTH was enhanced,the quantity of the antibody-producing cell and the blood-serum erythrocytolysin were raised up.When the dose reached to 150mg·kg-1,the immunity-enhancing effect was obvious.This research suggested that freeze-drying natto powder could enhance mice immune function

Preparation and quality control of Mango Cough Mixture

目的:制备芒果止咳合剂并建立其质量控制方法。方法:采用微波提取法制备芒果止咳合剂;以化学法和薄层色谱(TlC)法鉴别芒果苷;以高效液相色谱(HPlC)法测定芒果苷的含量。结果:化学法和TlC能清晰地鉴别芒果苷;芒果苷进样量在4~14μg范围内线性关系良好(r=1.0000);加样回收率为96.78%(rSd=2.00%)。结论:本制剂制备方法简便,稳定性良好。TlC法专属性强,HPlC法简便、准确,可用于芒果止咳合剂的质量控制。Objective: To prepare Mango Cough Mixture and establish its quality standard.Methods: The methods of microwave extraction was adopted to prepare for the mango cough mixture.Chemistry and TLC were used to identify Mangigerin, and HPLC was used to determine the content of Mangigerin.Results: Mangigerin was clearly identified with chemistry and TCL.A good linearity was seen of Mangigerin in the range of 4-14 μg (r=1.000 0).The recovery rate was 96.78% (RSD =2.00% ).Conclusion: The preparation is simple in preparation technique and good in stability.The TLC method is highly exclusive.The HPLC method is simple, accurate, and can be used for the quality control of Mango Cough Mixture

甲氨蝶呤磷脂复合物纳米粒的制备及表征

研究甲氨蝶呤磷脂复合物纳米粒的制备方法并进行表征。以卵磷脂(PC)为材料,甲氨蝶呤(MTX)为模型药物,采用共溶剂法制备MTX-PC复合物,用薄膜分散法将MTX-PC复合物自组装成纳米粒,并对其进行质量评价与体外释药试验。MTX-PC复合物纳米粒为类似脂质体的球形结构,粒径均匀,分散性好,平均粒径为(152. 5±3. 2) nm、多分散系数为0. 162±0. 015、电位为-(20. 3±2. 1) m V、载药量为(20. 7±2. 4)%;且MTX以非晶型状态均匀分布在纳米粒中。其在3种p H值条件下的体外释放随着p H值的下降而上升,在模拟肿瘤弱酸性环境的p H 5. 0下,48 h药物累积释放量高达90%。MTX-PC复合物纳米粒具有缓释的特点,且在肿瘤环境中利于药物的释放,有肿瘤治疗的潜力。厦门市科技计划惠民项目(No.3502Z20174071

Preparation of Chitosan Nanoparticles for Targeting and Sustained Drug Delivery System by Ion-induced Combined with Chemical Crosslinking

目的制备粒径相对可控的壳聚糖纳米粒,探索其在药物缓释体系中的应用。方法以多聚磷酸钠为离子诱导剂、戊二醛为化学交联剂,通过离子诱导结合化学交联法,制备壳聚糖纳米粒;在1-乙基-(3-二甲氨基丙基)碳二亚胺盐酸盐(EdC)作用下,分别进行丝裂霉素载药以及聚乙二醇(PEg),叶酸修饰;另外,对载药纳米粒子进行不同PH条件下的体外释药实验;对PEg,叶酸修饰的壳聚糖纳米粒罗丹明b荧光标记后,进行激光共聚焦以及活体成像实验。结果离子诱导交联法可以获得粒径范围在200--500 nM的壳聚糖纳米粒;丝裂霉素载药量可以达到25%,包封率为50%,体外释药呈现突释和缓释双相特征,并且随着PH的升高释药明显加快;未经修饰的、叶酸修饰的以及PEg和叶酸修饰的纳米粒都能有效的进入HElA细胞,而单独PEg修饰的却很少进入细胞内;叶酸修饰的纳米粒有明显的靶向作用,PEg修饰的纳米粒可以明显延长实验裸鼠血液中循环时间。结论采用离子诱导结合化学交联法可以获得粒径可控、稳定、适合于主动靶向给药的壳聚糖纳米粒。OBJECTIVE To prepare chitosan nanoparticle with controllable size and investigate its applications to targeting and sustained drug delivery system.METHODS The combination of an ion-induced and chemical crosslinking method was used to prepare chitosan nanoparticles,and mitomycin C,PEG and folic acid were bound covalently on the surface of chitosan nanoparticles in the presence of 1-ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride(EDC),respectively.In vitro drug release test was carried out in different pH PBS solution.Confocal laser scanning microscope of Hela cell and in vivo imaging test were carried out using PEG and folic acid-modified chitosan nanoparticles labeled by Rhodamine B.RESULTS The diameter was in the range of 200 and 500 nm,the drug-loading capability and entrapment efficiency were 25% and 50%,respectively.The drug release was somewhat biphasic with an initial burst effect,followed by a subsequent slower release.Furthermore,increasing pH of the medium resulted in a faster release rate.Blank chitosan nanoparticles,folic acid modified and both folic acid and PEG-modified nanoparticles were effectively uptaken by Hela cells,while the single PEG-modified nanoparticles rarely entered the cell.By live imaging techniques,folic acid-modified nanoparticles had a clear targeting character.While,the PEG-modified chitosan nanoparticles enhanced circulation time in the bloodstream of mice.CONCLUSION By the method of ion-induced combined with chemical crosslinking,steady chitosan nanoparticles with controlable size were obtained and suitable for active targeting drug delivery.国家重大基础研究计划项目(973项目)资助(2006CB933300);厦门市科技计划项目(3502Z20093009

肝脏肿瘤诊断和治疗双功能超声造影剂的制备及实验研究

目的探索载羟基喜树碱的聚乳酸微泡的制备及超声辐照下对肝脏肿瘤细胞生物效应的影响。方法采用DMSO溶解HCPT,使HCPT大部分以内酯环闭环形式存在,应用改良的乳化-溶剂挥发法,制备载羟基喜树碱的聚乳酸微泡。结果以载羟基喜树碱的聚乳酸微泡载药量和包封率分别达到1.69%和62.2%;超声介导下载药微泡5d累积释药量接近80%。结论通过改变载药方式,可以制备出抗肝脏肿瘤活性更高的药物制剂

Antitumor effect of hydroxy camptothecin-loaded amphiphilic block copolymer nanoparticles

目的研究羟基喜树碱双嵌段共聚物纳米粒（MePEG．PLGA．HCPT．NPs）的抗肿瘤作用。方法选择人肝癌细胞株Bel-7402为体外模型，采用MTT法观察体外肝癌细胞的生长和增殖抑制情况，评价MePEG-PLGA-HCPT-NPs对肝癌细胞的毒性作用；采用激光共聚焦荧光显微镜技术观察其对肝癌细胞摄取药物的影响；采用小鼠H22肝癌细胞实体瘤模型进行体内抑瘤实验观察荷瘤动物的生长情况，测定肿瘤生长抑制率。结果MePEG—PLGA-HCPT．NPs能抑制肝癌细胞的生长增殖，且随羟基喜树碱浓度的升高而增强；激光共聚焦荧光照片显示载药纳米粒能有效地被Bel．7402细胞摄取；MePEG-PLGA-HCPT-NPs对小鼠的H22实体瘤生长具有明显的抑制作用，低、中、高剂量组的生长抑瘤率分别为37．62％、50．31％和70．25％，与对照组相比差异均有统计学意义（P〈0．05）。结论MePEG-PLGA-HCPT-NPs具有较强的体外、体内抗肿瘤作用。与羟基喜树碱注射剂相比，MePEG-PLGA-HCPT-NPs的抑瘤率更高，且与剂量有关，并对肿瘤生长的抑制更为持久。AIM To study the antitumor effect of hydroxy camptothecin（HCPT）-loaded amphiphilic block copolymer nanoparticles（MePEG-PLGA-HCPT-NPs）. METHODS The human hepatoma cell lines Bel-7402 in vitro were selected as model, the cell growth and viability inhibited by MePEG-PLGA-HCPT-NPs were observed and the antitumor cytotoxicity was evaluated by MTT assay. Cellular uptake of HCPT was observed by Confocal fluores- cence microscopy（CLSM）. Hepatocellular carcinoma cell H22 was subcutaneously injected into mice and MePEG- PLGA-HCPT-NPs was administered to the tumor-bearing mice. The growth of tumor was measured, and the inhibi- tory rate of tumor growth was calculated. RESULTS Hepatoma cell growth and viability were inhibited by Me- PEG-PLGA-HCPT-NPs, the inhibition was enhanced with increasing concentrations. CLSM photos indicated that MePEG-PLGA-HCPT nanoparticles enhanced the intracellular uptake of HCPT in Bel-7402 ceils. Marked inhibitory effect of MePEG-PLGA-HCPT-NPs on the transplanted hepatocellular carcinoma H22 was observed in the tumor- bearing mice. The inhibitory rates were 37.62% , 50.31% and 70.25% in the groups treated with low, medium and high dosage of MePEG-PLGA-HCPT-NPs, respectively （P 〈 0. 05 vs control group）. CONCLUSION Me- PEG-PLGA-HCPT-NPs has marked inhibitory effects on tumor growth in vitro and in vivo. The inhibitory effect of MePEG-PLGA-HCPT-NPs is obvious and dose-dependent and higher than that of HCPT injection.福建省医学创新课题项目（编号2014-CXB-35）;厦门市科技计划指导性项目（编号3502220159001

Role of Nrf2/ARE in chemoprevention of cancer

化学致癌过程是涉及启动、促进和进展等多阶段的复杂过程。癌症的化学预防是应用天然的或合成的化学物质,以阻断、抑制或其癌变过程,从而达到预防肿瘤的目的。化学致癌物的体内生物转化依靠肝脏的Ⅰ相和Ⅱ相代谢相酶来完成。作为对化学预防剂的应答反应,碱性亮氨酸拉链蛋白家族成员转录因子Nrf2首先从胞质蛋白Keap1上解离,然后发生核内转位,与Ⅱ相代谢酶基因上游的抗氧化反应元件结合诱导Ⅱ相代谢酶基因的表达,这是化学防癌的重要机制;Nrf2/ARE对Ⅱ相代谢酶的调节涉及PI3K、MAPK、PKC等细胞内重要信号传导途径。这些发现加深了化学防癌机制的认识并为评估潜在抗癌物质提供了新的策略。 【英文摘要】 Chemical carcinogenesis is involved in complicated multiple stages of initiation,promotion and progression.Chemoprevention comprises multiple intervention methods using either pharmacological or dietary agents to impede,arrest,or reverse carcinogenesis at various stages.Biotransformation of carcinogens may be associated with hepatic phase Ⅰ and Ⅱ detoxifying enzymes.It is proved that Nrf2,a member of the basic-leucine zipper family of transcription factors,is dissociated from cytoplasmic protein Keap1 first..

Effect of Helix-pin Composite Tissue Flap in the Treatment of Partial Auricle Defect

目的介绍一种修复外伤性小面积耳郭缺损的手术方法。方法根据外伤性部分耳郭缺损患者的耳郭形态,尤其是耳轮脚明显、耳郭缺损位于耳轮部,面积约2CMx0.8CM以下的外伤后患者,采用耳轮脚复合组织瓣游离移植进行缺损修复。结果本组7例患者,术后伤口一期愈合,缺损修复满意,耳郭外形良好。结论耳轮脚复合组织瓣游离移植,治疗外伤性小面积耳郭缺损,尤其是耳轮部缺损,可取得满意效果。Objective To explore the effect of helix-pin composite tissue flap in the repairing of partial auricle defect.Methods Seven cases were treated by using this flap.According to the shape of auricle defect,helix-pin composite tissue flap of auricle was used in those people who have distinct crus of helix and the area of defect was less than 2.0 cm × 0.8 cm.Results All flaps obtained healing by first intension and good contour.Conclusion Repairing defect of partial auricle with helix-pin composite tissue flap is a safe and reliable mothod with satisfactory repairing result

牡蛎壳纳米羟基磷灰石的制备与表征

以僧帽牡蛎壳粉末为原料,通过水热反应合成纳米羟基磷灰石(n-HA),考察反应时间、反应温度、反应物摩尔比及牡蛎壳粉末的微结构对反应的影响.运用X射线衍射(XRD)、扫描电子显微镜(SEM)、红外光谱(FTIR)、X射线能谱仪(EDS)及MTT实验表征产物的晶相组成、形貌、化学组成及细胞相容性.结果显示,牡蛎壳粉末经水热反应后仍保持其原有形貌,产物为部分CO32-取代的片状n-HA,其Ca/P摩尔比约为1.5,其结构及组成与人骨HA相似,细胞相容性良好.牡蛎壳粉末外表面方解石通过溶解重结晶过程转化为片状n-HA,内部方解石则经由固态局部规整离子交换反应转化为n-HA.最佳水热反应条件为220℃下反应6 h,牡蛎壳中Ca与(NH4)2HPO4中P摩尔比为5∶6

Intratumoral Chemotherapy with an Implantable Collagen Film Impregnated with Epirubicin-loaded Polylactic Acid Microspheres Inhibits Tumor Growth in Hepatocellular Carcinoma Xenografts

[中文文摘]制备用于实体肿瘤局部治疗的植入型表阿霉素缓释药膜。采用复乳-溶剂挥发法制备聚乳酸载表阿霉素缓释微球,用交联复合法制备含载药微球的植入型胶原药膜;用扫描、透射电镜、共聚焦及粒度仪等考察微球和药膜的形貌、结构、粒径及体外释放;用H22肝癌荷瘤动物模型评价其体内抑瘤效果。结果:载药微球粒径分布均匀,外观圆整,平均粒径为5.81μm;微球的载药量4.39%,包裹率为37.2%;10h内载药微球在模拟体液中的累积释放率为35%;腹腔注射载药微球与瘤体局部植入胶原药膜对H22肝癌均有明显的抑瘤效果;微球注射与药膜植入两种不同给药方式对H22肝癌抑瘤效果也存在显著性差异(P<0.05)。植入型载表阿霉素缓释胶原膜具有良好的药物局部缓释特性,在肿瘤的术后局部治疗方面具有良好的临床应用前景。[英文文摘]Drug-releasing implants delivering chemotherapeutic agents can provide promising local therapy to patients with malignant disorders.The purpose of the present study was to develop implantable collagen film impregnated with epirubicin-loaded polylactic acid(PLA) microspheres(EPI-PM) for intratumoral administration in solid tumors.EPI-PM was prepared by double emulsion-solvent evaporation method,and the microspheres were further incorporated in biodegradable chemically cross-linked collagen to formulate implantable collagen film. The microspheres were characterized by scanning electron microscope , transmission electron microscope and laser confocus microscopy. In vitro release of epirubicin was examined by ultraviolet spectrophotometry. Transplantable murine hepatoma 22 (H22) model was used to evaluate the effects of EPI-PMor collagen film impregnated with EPI-PMon murine liver cancer.The results indicated that the epirubicin was well incorporated and dispersed homogeneously in PLA. The EPI-PM was uniformly spherical with average diameter of 5181μm, drug loading of 4139% , and embedding ratio of 3712%. The cumulative drug release rate of EPI2PM was 35 % in analog body fluid at the 10h. The tumor growth rate was significantly inhibited by intraperitonal injection of EPI2PMor intratumoral implantation of collagen film impregnated.国家重大科学研究计划项目(2006CB933300); 福建省自然科学基金(C0610045); 厦门市科技计划项目(3502Z20055007); 厦门市科技创新资金项目(3502Z20041029)