积雪草苷平衡溶解度和油水分配系数的测定

目的测定积雪草苷在不同pH介质中的平衡溶解度和正辛醇-水/缓冲液体系中的表观油水分配系数（Papp）。方法采用RP-HPLC法测定积雪草苷浓度,研究其在水和不同pH介质中的平衡溶解度;采用摇瓶法测定积雪草苷在正辛醇-水/缓冲液体系中的Papp。结果 25℃下积雪草苷在水中的平衡溶解度为305.02μg.ml-1,在pH 5.0缓冲液中平衡溶解度更低;积雪草苷在正辛醇-水中Papp为0.908（logPapp=-0.042）,在pH 5.0缓冲液中Papp最高。结论积雪草苷为亲水性药物,但其在水中的溶解度较小。在pH 5.0～8.0范围内,积雪草苷的平衡溶解度随pH的增加而增加,相反油水分配系数随pH的增加而减少。     

高效液相色谱法测定特考韦瑞的平衡溶解度和油水分配系数

目的 用高效液相色谱法(HPLC)测定特考韦瑞(ST-246)在37℃水和不同pH缓冲液的平衡溶解度,以及在正辛醇-水/缓冲液系统的油水分配系数.方法 采用摇瓶法测定平衡溶解度,通过药物分配平衡后在油相及水相的浓度比,计算油水分配系数.结果 ST-246在37℃水的平衡溶解度为3.35 mg/L,ST-246的表观油水分配系数为230.49(lgP=2.36),在正辛醇/pH4.0缓冲液的油水分配系数最大,为779(lgP=2.89).结论 ST-246的水溶性较差,脂溶性不佳,其水中溶解度呈pH依赖性,增大pH可增加其溶解度.     

蟾酥β—环糊精包合物的理化性质考察

目的　考察蟾酥 β -环糊精的理化性能。 方法　采用薄层色谱、X -射线粉末衍射及红外光谱法对包合物进行了理化鉴别 ,采用紫外光谱法考察包合物中蟾毒配基类化合物的溶解度和体外溶出度。结果　薄层色谱图谱显示 ,蟾酥被 β -环糊精包合前后的主成分没有发生变化 ,包合物的X -射线粉末衍射图谱及红外光谱与蟾酥、蟾酥 β -环糊精混合物的图谱具有显著性差异。包合物中蟾毒配基类化合物在 0 .1mol·L-1盐酸溶液、pH6 .6和pH7.5磷酸盐缓冲液中的溶解度及体外溶出速率均有显著提高。结论　蟾酥被 β-环糊精包合后呈现出新的物相特征 ,与蟾酥相比其理化性质有较显著的改变     

喷雾干燥法制备盐酸异丙嗪－β环糊精包合物的实验研究

目的：采用喷雾干燥法制备,以提供一种新的包合物制备方法。方法：以βCD为包合材料,按1：1摩尔比加入PMH,制成PMH－βCD溶液。在一定喷雾条件下喷雾干燥,制成PMH－βCD包合物。并以冷冻干燥法为对照,进行X－射线衍射,差示量热扫描等分析。结果：喷雾干燥法制备的PMH－βCD包合物与冷冻干燥法有同样的X射线衍射图谱和DSC图谱,表明已形成包合物。包合物在喷雾干燥过程中,其理化性质未发生变化。结论：喷雾干燥法可替代冷冻干燥法制备盐酸异丙嗪包合物。     

超声波技术制备聚乙二醇/蒙脱石插层复合物

目的:为探讨复合材料的结构及功能提供基础数据.方法:采用X-射线衍射(XRD)分析超声波振荡聚乙二醇(PEG)/蒙脱石(MMT)插层复合物的结构.结果:较大分子量的PEG与蒙脱石插层后的层间距更大.结论:较高相对分子质量的PEG与蒙脱石层间距有较强的结合能力.     

姜黄素甲基化-β-环糊精包合物制备工艺研究

 目的 制备姜黄素甲基化-β-环糊精包合物,改善其在水中溶解度.方法 采用饱和溶液法制备姜黄素甲基化-β-环糊精包合物,以包合物溶解度为评价指标,筛选最佳包合处方和工艺,以差示扫描量热法(DSC)和X射线衍射法对包合物进行确证.结果 最佳包合工艺:姜黄素和甲基化-β-环糊精投料摩尔比为1∶2,包合温度为45℃,反应时间为2 h.测得姜黄素甲基化-β-环糊精包合物的水中溶解度约为10 mg/ml.结论 姜黄素经包合后在水中溶解度提高了约500倍.     

硅质体作为新型药物载体的研究进展

脂质体（liposome）是磷脂分散在水中时形成的脂质双分子层,又称为人工生物膜.自1971年首次作为药物载体应用以来,由于其良好的生物相容性、靶向性及缓释特性,使其成为世界上生物医药领域最热门的靶向给药技术[1].但由胆固醇和磷脂构成的传统脂质体存在体内外稳定性差、靶向性不理想等缺点,因而限制了脂质体的临床应用和工业化生产[2].     

含镁脱细胞牛骨基质的制备与性能评估

目的 制备含镁脱细胞牛骨基质(ABBM-Mg)并对其微观结构和理化性能进行评估.方法 将冻干ABBM在2 mol/L镁离子溶液中浸泡7 d获得复合材料,用扫描电镜(SEM)和能谱分析仪(EDS)观察其微观结构并分析元素组成;X射线衍射(XRD)分析复合材料的物相组成;傅里叶红外光谱(FT-IR)检测材料的官能团;电感耦...     

人类解旋酶样转录因子介导辐射凋亡细胞DNA修复蛋白的降解

目的 探讨人类解旋酶样转录因子(HLTF)转染对辐射诱导细胞凋亡时DNA修复相关蛋白水平的影响。方法 将野生型和RING结构域突变型 HLTF 分别转染人肺癌细胞A549,⁶⁰Co γ射线15 Gy照射诱导细胞凋亡, 用Western blot 检测HRAD17和HRAD52蛋白水平的变化,免疫共沉淀检测特定复合物的存在。结果 γ射线诱导细胞凋亡时, 野生型 HLTF 转染组与对照组相比,DNA修复蛋白HRAD17和HRAD52水平明显降低,而RING结构域突变组与对照组相比则没有明显变化;辐射诱导细胞凋亡时,HLTF可与HRAD17和HRAD52形成复合物。结论 HLTF可介导辐射诱导的凋亡细胞中HRAD17和HRAD52的降解, 其机制可能是通过蛋白质复合物的相互作用使DNA修复蛋白泛素化而降解。     

含银海藻酸盐敷料理化性质及其抗菌性能的研究

目的：探索含银海藻酸盐敷料的理化性质、生物安全性及抗菌活性。方法通过扫描电子显微镜（ SEM ）等实验方法对含银离子海藻酸盐敷料进行形貌及理化特征分析;通过MTT法,检测敷料的生物安全性;结合体外抑菌实验,研究敷料的抗菌效果。结果与海藻酸钙敷料相比,3种不同含量的银离子敷料透气率无显著差异（P＞0．05）;银离子浓度越高,其溶胀比率越高,吸水能力越强,降解越慢;MTT结果显示,细胞毒性较低;体外抑菌实验证实,银离子敷料对革兰阳性、阴性菌均具有良好的抑菌作用,同时显示银离子浓度越高,其抑菌效果越好。结论含银海藻酸盐敷料具有良好的生物相容性和抗菌活性,在创面愈合治疗中具有潜在的应用前景。     

Investigation of the magnetic properties of iron oxide nanoparticles used as contrast agent for MRI.

Superparamagnetic iron oxide particles, a new class of contrast agents for MRI, are extremely good enhancers of proton relaxation. However, the development of such particle systems has resulted in a wide range of preparations whose physico-chemical properties differ greatly. We have conducted a set of physical experiments: X ray diffraction analysis, relaxivity measurements, susceptibility determinations, and thermomagnetic cycling on different preparations of superparamagnetic particles. Our results demonstrate a good correlation between susceptibilities measured in liquid samples at room temperature and the R2/R1 ratio. Susceptibility measurements between liquid nitrogen temperature and room temperature show three different types of behavior dependent on the size of iron oxide crystals. Comparison of heating and cooling curves from strong field thermomagnetic cycles provides information about the maghemite/magnetite crystal content. The information on magnetic properties reported in this study may help to characterize and to select these materials for use as MRI contrast agents.     

NMR measurement of the degree of oil/water partition of paramagnetic contrast media

Magnetic resonance imaging techniques have been used to evaluate the oil/water partition of a series of stable nitroxide free radicals. The degree of partition, K, closely parallels the order of chemical polarity and lipophilicity of these compounds. This method also provides insight into both their nuclear magnetic resonance relaxation characteristics and pharmacokinetics.     

Comparison of technetium-99m aminoalkyl diaminodithiol (DADT) analogs as potential brain blood flow imaging agents

N-ethyl piperidinyl diaminodithiol (NEP-DADT), complexed with 99mTc has been developed as an agent for the measurement of brain blood flow using SPECT. Studies in patients have shown that 99mTc NEP-DADT enters rapidly into the brain, but also clears rapidly (t1/2 = 17 min). In this study nine new aminoalkyl DADT derivatives were synthesized, labeled with 99mTc and tested in mice with the aim of developing an agent with increased retention in the brain. In addition, relationships between chemical properties of the derivatives and their in vivo localization were investigated. The results were as follows: (a) the R-group and its isomeric configuration has a profound influence on the biodistribution; (b) 99mTc aminoalkyl DADT derivatives with apparent pKa values of greater than 6.9 show poor brain uptake (less than 0.40% dose at 5 min); (c) lengthening of the chain between the DADT moiety and the amino-R group from ethyl to hexyl generally increases the apparent pKa and consequently lowers brain uptake; (d) a correlation (r = 0.71) exists between initial brain uptake and the octanol-buffer partition coefficient; (e) 99mTc-4'-methyl NEP-DADT has the highest partition coefficient, relatively high uptake, and longest retention in the mouse brain. This complex has characteristics suited for brain blood flow measurements.     

低频超声联合苦参素对人卵巢癌OVCAR-3细胞生物学特性影响

目的研究低频超声和苦参素联合应用对人卵巢癌OVCAR-3细胞生物学行为的影响。方法培养人卵巢癌OVCAR-3细胞,采用随机分组分为4组:对照组、低频超声组、苦参素组和联合组(低频超声+苦参素)。分别给予如下处理:低频超声组为超声840 k Hz,0.75 W/cm~2×3 min辐照;苦参素组为药物浓度为10 mg/ml培养24 h;联合组叠加处理因素。应用CCK-8检测各组细胞增殖;流式细胞仪检测各组细胞凋亡;Transwell实验检测细胞侵袭能力。结果单独应用低频超声或苦参素均可抑制OVCAR-3细胞增殖、诱导细胞凋亡、促进细胞侵袭。与单独应用组相比,低频超声和苦参素联合,上述作用显著增强。结论低频超声可增强苦参素诱导的抑制卵巢癌细胞增殖、侵袭能力以及诱发凋亡的作用。     

Prediction of 99mTc-biguanide complex structures and their interactions with biological molecules by molecular mechanics calculations

The structures of some Tc-biguanide complexes are predicted by molecular mechanics calculations. In addition, simulations of molecular interactions between the predicted equilibrium structures with water molecules or peptide chains are correlated with experimental data of partition coefficients and percentage of human protein binding, evaluated for the analogous 99mTc-biguanide complexes. These results suggest the value of computer-assisted design of new Tc-radiopharmaceuticals, and in particularly, stress the great interest of using molecular modelling to predict molecular properties that can be successfully correlated with results obtained by in vitro studies.     

Tropolone: A lipid solubilizing agent for cationic metals

Lipid soluble agents which chelate radioactive cations have several potential uses in nuclear medicine including: brain imaging, labeling of blood elements, and identifying fatty infiltration of organs. A tropolone-gallium complex has been characterized by the determination of in vitro partition ratios correlated with in vivo organ distribution in the rat. Partition ratios were determined for gallium-67 citrate, indium-114m chloride, and iron-59 chloride cations complexed with tropolone in chloroform+water, octanol+water, olive oil+water, and olive oil+plasma two-phased systems. Tropolone proved to be highly effective in the lipid solubilization of these metal cations. Distribution studies in animals of these cations complexed with tropolone demonstrated an increased concentration of these cation complexes in tissues of high lipid content when compared with appropriate controls.     

99mTc]Ca-phytate: some colloidal characteristics related to the optimal preparation conditions

Some physico-chemical characteristics of the colloidal radiopharmaceutical [99mTc]Ca-phytate related to optimal preparation conditions have been studied. It is demonstrated that the Ca2+-phytate stoichiometry is 6:1. Two different Ca-phytate colloids seem to be formed, mainly depending on the Ca2+:phytate molar ratio--one of low mycelar size for a 1:1 Ca2+:phytate molar ratio (cmc = 5.10(-5) M), and another one, with a higher mycelar size for a 6:1 molar ratio (cmc = 8.10(-5) M). This last one it probably better for providing a good quality splenic uptake.     

An admonition when measuring the lipophilicity of radiotracers using counting techniques.

Log P measurements are a fundamental physico-chemical parameter and one of the cornerstones of structure activity relationships in medicinal chemistry. Despite the attractiveness of the method, the use of counting techniques to measure the log P of lipophilic radiotracers is fraught with pitfalls due to the amplifying effects of small quantities of radioactive impurities. For example, a radiotracer with a log P of 4 containing only 0.1% of a radioactive impurity with a log P of -1 will have an apparent log P of 3 if measured using conventional shake-flask partition techniques, counting the radioactivity in each phase. However, pre-washing the radiotracer-containing organic phase with aqueous phase can, in many cases, allay doubts about the validity of such measurements.