冬凌草甲素/胆固醇甲酰-壳聚糖共聚物纳米胶束的制备及其体外抗肿瘤作用

 目的 制备冬凌草甲素/胆固醇甲酰-壳聚糖共聚物（ORI/CF-CS）纳米胶束并研究其体外抗肿瘤活性。方法 采用酰胺化反应合成胆固醇甲酰-壳聚糖共聚物（CF-CS）;以CF-CS为载体材料制备ORI/CF-CS纳米胶束,并测定其载药量、包封率、形态、粒径和ξ电位;MTT法测定其对宫颈癌Hela肿瘤细胞的细胞毒作用。结果 ORI/CF-CS纳米胶束载药量为9.16%,包封率为48.83%,粒径控制在68.10~113.8 nm内,ξ电位为-34.97~-29.19 mV,体外释药缓慢;ORI/CF-CS纳米胶束对Hela肿瘤细胞的细胞毒作用优于冬凌草甲素溶液,且IC₅₀ 值比冬凌草甲素溶液低约3倍。结论 CF-CS是冬凌草甲素的优良载体,且可提高其抗Hela肿瘤细胞的活性。     

重组水蛭素-2鼻腔给药纳米粒制备工艺研究

目的 优选重组水蛭素-2 (rHV2)鼻腔给药纳米粒最佳制备工艺.方法 采用壳聚糖与三聚磷酸钠复凝聚法,以包封率、载药量等为评价指标,以单因素考察和正交试验设计,对壳聚糖黏附纳米粒制备过程中有关影响因素及工艺参数进行优化.结果 壳聚糖的类型、壳聚糖溶液的pH值、壳聚糖与多聚磷酸钠的最终质量比以及搅拌速率对rHV2纳米粒的包封率和载药量均有较显著影响;优选工艺的包封率可达到70％以上,载药量＞8％.结论 经优选的工艺稳定可靠,可用于rHV2鼻腔给药纳米粒的制备.     

冬凌草甲素胆盐/磷脂-混合胶束的制备及其性质研究

目的:研究冬凌草甲素胆盐/磷脂-混合胶束的制备与性质。方法:采用共沉淀法制备冬凌草甲素胆盐/磷脂-混合胶束。利用高效液相色谱法,考察不同影响因素情况下(磷脂比例、辅料总浓度、pH值、离子强度、水化介质温度),冬凌草甲素在混合胶束中的溶解性情况。利用高效液相色谱法,考察了胶束的稀释稳定性。通过激光粒度仪测定了粒径分布和电位,通过透射电子显微镜测定了胶束粒径及表面形态。结果:优化工艺条件为:25℃超纯水作为水化介质;磷脂比例在0～0.6范围内,增加磷脂比例,冬凌草甲素溶解度范围为(11.25±0.35)mg/mL～(4.66±0.41)mg/mL;辅料总浓度在1%～10%范围内,增加辅料总浓度,冬凌草甲素溶解度范围为(3.77±0.40)mg/mL～(19.74±0.96)mg/mL,载药量范围为(37.73±3.97)%～(19.74±0.96)%。胶束具有较好的稀释稳定性。载药胶束粒径为(10.92±2.90)nm,Zeta电位-(48.75±2.37)mV,胶束为类圆形实体,分布均一。结论:胆盐/磷脂混合胶束系统能够显著增加冬凌草甲素的溶解性,可获得较为理想的粒径分布;有望开发成为冬凌草甲素的新型药物传递系统。     

冬凌草甲素硬脂酸固态类脂纳米粒的实验研究

 目的 以冬凌草甲素为模型药物,以硬脂酸为载体材料制备冬凌草甲素固态类脂纳米粒,并考察其质量和性质。方法用乳化蒸发-低温固化技术制得了冬凌草甲素固态类脂纳米粒,并对其形态、粒径、表面电位、包封率、结构和质量、体外释药特性等进行了研究。结果 得到的硬脂酸固态类脂纳米粒为类球形实体,粒径分布比较均匀,平均粒径d_av=(22.22±15.5)nm;ξ电位-45.07mv;包封率为(44.83±1.504)％;药物体外释放符合Higuchi方程。用DSC和X-射线衍射分析证明纳米粒确已形成。结论 冬凌草甲素可以制成硬脂酸纳米粒,各项物理指标稳定。     

应用Box-Behnken实验设计优化水飞蓟素固体脂质纳米粒处方研究

目的应用Box-Behnken实验设计,优化水飞蓟素固体脂质纳米粒的最佳处方。方法采用三因素三水平Box-Behnken实验设计,以水飞蓟素为模型药物,采用乳化蒸发-低温固化法制备固体脂质纳米粒。利用效应曲面法对影响固体脂质纳米粒包封率、载药量和粒径的主要因素进行考察,以包封率、载药量和粒径为响应值,建立相应的二项式数学模型优化处方。结果最优处方为固体脂质纳米粒中脂质单硬脂酸甘油酯量为5.05%,7.25%Poloxmer 188作为乳化剂,药物的量为15%。结论采用Box-Behnken实验设计可用于水飞蓟素固体脂质纳米粒的处方优化筛选。     

介孔二氧化硅纳米粒对黄酮类化合物载药性能及药物释放的影响

目的制备介孔二氧化硅纳米粒,并研究其对黄酮类化合物(芹菜素、槲皮素、橙皮素)载药性能及药物释放的影响。方法制备负载黄酮类化合物的介孔二氧化硅纳米粒,扫描/透射电镜、傅里叶红外光谱仪、X射线衍射、氮气吸附-脱附解析对其进行表征,高效液相色谱仪测定纳米粒的载药量。结果所得纳米粒形状大小均一,平均粒径230~250 nm,比表面积为1 045 cm2/g,孔径2.8 nm。橙皮素、槲皮素和芹菜素的载药量分别为27%、23%和18%,40 min时的释放量分别为84%、80%和76%。结论介孔二氧化硅纳米粒可实现黄酮类化合物的高负载,并显著提高其在水溶液中的溶出度。     

载汉黄芩素的mPEG-PLGA纳米粒的制备及体外评价

目的制备载汉黄芩素的mPEG-PLGA纳米粒,并对其性能进行体外评价。方法以mPEG-PLGA为载体材料,采用溶剂扩散法制备载汉黄芩素的纳米粒,考察其形态、载药性能、血清稳定性和体外释放行为等指标。结果制得的汉黄芩素纳米粒外观圆整,粒径为(112±33)nm;载药量为(3.27±0.04)%;纳米粒在50%胎牛血清中稳定;pH 7.4磷酸盐缓冲液中24 h累积释放率约为39%,血浆对其释放行为无明显影响。结论制得的汉黄芩素纳米粒具有明显的药物缓释效果和良好的血清稳定性。     

叶酸偶联华蟾素壳聚糖纳米粒的制备及其特性研究

目的:制备叶酸偶联壳聚糖载华蟾素纳米粒,并检测其体外性质。方法:首先合成叶酸偶联壳聚糖,再制备负载华蟾素的叶酸偶联壳聚糖纳米粒,并测定叶酸偶联华蟾素壳聚糖纳米粒的载药量、包封率及累积释药量。结果:制备了叶酸偶联华蟾素壳聚糖纳米粒,载药量为9.7%,包封率为61.3%,12h累积释药量为42.6%,72h累积释药量为63.3%。结论:叶酸偶联华蟾素壳聚糖纳米粒制备工艺简单,性能较好。     

可生物降解聚合物纳米粒的研究进展

目的：介绍可生物降解聚合物纳米粒的研究进展，以推进新制剂的开发研究。方法：以大量的具有代表性的参考文献为依据，从可生物降解聚合物纳米粒的制备方法、载药机制、体外药物释放、纳米粒表面特性和修饰方法及作为多肽蛋白质药物传递系统载体等方面进行综合和归纳。结果与结论：可生物降解聚合物纳米粒给药系统是有广阔发展前途。     

HPLC测定鹰嘴豆芽素A2种脂质纳米粒包封率和载药量

目的:建立鹰嘴豆芽素A固体脂质纳米粒(BCA-SLN)和纳米脂质载体(BCA-NLC)的包封率和载药量的高效液相色谱测定方法.比较2种纳米粒包封率和载药量的差异.方法:采用超滤离心法分离游离药物,高效液相色谱法测定药物含量.Cosmosil C18色谱柱(4.6 mm×250 mm,5μm);柱温30℃;流动相乙腈-0.1％磷酸(60∶40);流速1 mL·min-1;检测波长260 nm.结果:BCA在0.005 ～5.000 mg· L-1线性良好(r=1.000).所制BCA-SLN包封率为(97.15 ±0.28)％,载药量为(6.38±0.043)％;BCA-NLC包封率为(99.57±0.11)％,载药量为(6.91±0.044)％.比较2种纳米粒包封率和载药量表明均存在显著性差异(P≤0.05).结论:采用高效液相色谱法结合超滤离心法测定BCA 2种纳米粒包封率和载药量方法准确、高效,NLC具有更高的包封率和载药量.     

两性霉素B的聚乙二醇-聚乳酸胶束的制备及其体外释放动力学

 目的制备两性霉素B的聚乙二醇-聚乳酸嵌段共聚物胶束,对其物理化学性质和体外释药特性进行评价。方法采用阴离子聚合法合成了一系列聚乙二醇-聚乳酸嵌段共聚物;用透析法制备了聚合物胶束;用透射电镜观察了聚合物胶束的形态;用激光散射法测定了聚合物胶束的粒径及其分布;采取荧光探针法测定了聚合物的临界缔合浓度;用透析法考察了载药聚合物胶束的体外释放动力学。结果聚合物胶束大小均匀,具有球形核-壳结构,平均粒径范围为28～49nm,并随着疏水链段的增长,胶束粒径逐渐增大;3种聚合物的临界缔合浓度均较低,分别为1.87×10^-7,1.45×10^-7,9.61×10^-8mol·L^-1;两性霉素B聚合物胶束的体外释放缓慢,符合一级动力学特征。结论聚乙二醇-聚乳酸嵌段共聚物胶束可作为疏水性药物的纳米级长循环载体,具有很好的应用前景。     

紫杉醇mPEG-PLGA纳米粒的制备及其抗肿瘤作用研究

 目的探讨负载紫杉醇的聚乙二醇单甲醚-聚乳酸-乙醇酸(mPEG-PLGA)亲性嵌段共聚物纳米粒及其对肝癌H22细胞的体内抗肿瘤作用。方法采用界面沉积法制备紫杉醇mPEG-PLGA纳米粒(Ptx-Nps);应用透射电镜表征纳米粒的形态;粒径分析仪测其粒径及Zeta电位;研究mPEG在共聚物中的含量及紫杉醇投药量对纳米粒的影响;考察纳米粒对昆明小鼠肝癌H22的疗效和过敏实验。结果Ptx-Nps成球型,粒径为纳米级(<120 nm),均带负电荷(适合于静脉注射),与紫杉醇注射液(Ptx)相比,Ptx-Nps对肝癌H22的抑制作用比Ptx好。结论采用界面沉积法制备的纳米粒在紫杉醇投药量为1%,mPEG含量为4%时包封率最佳,本研究为开发紫杉醇新型静脉注射制剂提供了实验依据,mPEG-PLGA共聚物可成为抗肿瘤药物的理想新型载体。     

脑脉通治疗颈动脉粥样硬化斑块60例临床分析

目的：观察脑脉通治疗颈动脉粥样硬化斑块的临床疗效。方法：治疗组60例用脑脉通，对照组60例用舒降之治疗。结果：治疗组总有效率85．0％，对照组总有效率46．7％，两组比较有显著性差异(P＜0．05)。治疗组治疗后斑块体积明显减少、CCAD增加、IMT变薄、SV增加、DV增加、RI减少、PI增加，治疗前后比较有显著性差异(P＜0．05)。结论：脑脉通治疗颈动脉粥样斑块作用明显。     

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??OBJECTIVE To synthesize hyaluronic acid-octadecene (HOY) copolymers by terminal thiolation modification of hyaluronic acid (HA), prepare doxorubicin-loaded micelles and investigate its pharmaceutical characteristics. METHODS HOY copolymers were synthesized through Michael addition reaction. The doxorubicin-loaded copolymer micelles were prepared with ultrasonic method, then the particle size, Zeta potential, encapsulation efficiency, drug loading efficiency and in vitro release behavior were studied. RESULTS HOY copolymers were synthesized successfully. The particle size and Zeta potential of the drug-loaded micelles were (237.2??2.7) nm and (-22.37??0.38) mV, and the encapsulation efficiency and drug loading rate were (89.8??0.011)% and (5.4??0.007)%, respectively. Moreover, the accumulative release of doxorubicin in vitro was about 70% in 48 h, indicating that the drug was released slowly from the micelles. CONCLUSION This study develops a new micellar system based on terminal modified HA, and provides a reference for the study of HA nanocarrier.
     

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??OBJECTIVE To prepare heparan sulfate-vitamin E succinate (HDV) amphipathic copolymers and explore the pharmaceutical properties of doxorubicin (DOX)-loaded HDV copolymer micelles (DOX/HDV). METHODS HDV copolymers were prepared by amide reaction and its structure was confirmed by ¹H-NMR. DOX/HDV micelles were prepared by ultrasonic method. The particle size, morphology, Zeta potential, drug loading, entrapment efficiency, and in vitro drug release and cytotoxicity were evaluated. RESULTS HDV amphipathic copolymers were synthesized successfully. The particle size, PDI value and Zeta potential of drug-loaded micelles were (105.0??7.3) nm, (0.239??0.484) and (-21.4??2.6) mV, respectively. The encapsulation and drug loading rate were (76.22??0.76)% and (9.53?? 0.58)%, respectively. The results of drug release test in vitro showed that DOX was released slowly from the micelles. Cytotoxicity experiments indicated that blank micelles had no apparent toxicity against both tumor cells and normal cells. However, DOX/HDV micelles could inhibit the tumor cells growth obviously. CONCLUSION HDV copolymers can effectively load DOX with properties of drug sustained release and enhanced cytotoxicity against tumor cells in vitro, which indicates that HDV may be a potential candidate for cancer therapy.     

牛血清蛋白在聚酯-聚氨基酸生物降解材料中的稳定性

 目的：研究牛血清蛋白(BSA)在聚合物基质中的稳定性及影响因素。方法：合成含有甘氨酸的聚酯材料，制成含有BSA的基质，并进行稳定性研究。结果：在PCM材料中，甘氨酸的引入和材料的低吸水性提高了BSA的稳定性；在PLM材料中，甘氨酸和材料的高吸水性作用相反，BSA的稳定性取决于两者的综合效果。结论：引入甘氨酸改善了材料的亲水性。聚合物的组成和吸水对BSA的稳定性有很大影响。选用亲水性好但吸水量低的材料将提高蛋白质的稳定性.     

牛血清蛋白在聚酯聚氨基酸生物降解材料中的稳定性

目的：研究牛血清蛋白（ＢＳＡ）在聚合物基质中的稳定性及影响因素。方法：合成含有甘氨酸的聚酯材料，制成含有ＢＳＡ的基质，并进行稳定性研究。结果：在ＰＣＭ材料中，甘氨酸的引入和材料的低吸水性提高了ＢＳＡ的稳定性；在ＰＬＭ材料中，甘氨酸和材料的高吸水性作用相反，ＢＳＡ的稳定性取决于两者的综合效果。结论：引入甘氨酸改善了材料的亲水性。聚合物的组成和吸水对ＢＳＡ的稳定性有很大影响。选用亲水性好但吸水量低的材料将提高蛋白质的稳定性     

聚α-氨基酸膜的药物渗透性研究

 目的：研究炔诺孕酮(NG)对白氨酸-谷氨酸-谷氨酸甲酯共聚物膜的渗透性及其影响因素。方法：测定聚α-氨基酸膜的吸水率，NG对它的渗透系数以及缓释药囊的体外释药试验。结果：聚α-氨基酸膜的化学组成对它们的药物渗透性有极其重要的影响。聚合物的谷氨酸含量越大，其吸水率越大，NG对其的渗透性也越大。根据药物渗透系数求得释药速率的计算值与药囊体外释药试验的实验值是接近的。结论：聚α-氨基酸膜对药物的渗透系数是缓释药物装置释药速率研究的重要依据。     

Effects of electroacupuncture at Taichong(LR 3) and Baihui(DU 20)on cardiac hypertrophy in rats with spontaneous hypertension

OBJECTIVE: To investigate the effects of electroacupuncture(EA) at Taichong(LR 3) and Baihui(DU 20)on myocardial hypertrophy in spontaneously hypertensive rats(SHRs).METHODS: Thirty-six SHRs were randomly assigned to model, EA, and Losartan groups, with twelve rats per group. Twelve Wistar Kyoto rats were selected as the normal control group. Systolic blood pressure(SBP) and cardiac function were measured in all rats.Expression levels of factors associated with the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) pathway were evaluated by Western blotting and real-time PCR.Pathological changes of the heart tissue were observed by hematoxylin-eosin staining.RESULTS: After treatment, enhanced SBP was significantly decreased in the EA and Losartan groups compared with the model group(P 0.01). Echocardiographic and morphological analyses revealed that enhanced end-diastolic interventricular septal thickness and left ventricular posterior wall thickness, as well as ratio of left ventricular weight to body weight were markedly diminished in the EA and Losartan groups(P 0.01 or P 0.05), while reduced left ventricular end-diastolic dimension and left ventricular ejection fraction were significantly ameliorated(P 0.01). Real-time PCR and western blotting analyses showed that the expression levels of PI3K,Akt, and mT OR in SHRs were significantly up-regulated by EA and Losartan(P 0.01), while the expression levels of PTEN and ANP were down-regulated(P 0.01).CONCLUSION: EA at Taichong(LR 3) and Baihui(DU20) inhibited the development of cardiac hypertrophy and improved the cardiac function in SHRs, possibly through regulation of the PI3K/Akt/mTOR signalling pathway.     

通降和胃汤治疗胆汁返流性胃炎56例观察

目的：观察通降和胃汤治疗胆汁返流性胃炎的疗效。方法：将105例分为两组，治疗组56例，用自拟通降和胃汤，对照组49例用西沙比利治疗，疗程均为4周。结果：治疗组总有效率91.1％，对照组总有效率69．4％，两组比较有显著性差异（P〈0．05），治疗组疗效优于对照组。结论：通降和胃汤是治疗胆汁返流性胃炎的有效方剂。