HPLC-MS法研究碘化N-正丁基氟哌啶醇在兔体内的药代动力学

目的: 研究碘化N-正丁基氟哌啶醇(F2)在兔体内的药代动力学过程。方法: 6只新西兰兔耳缘静脉注射碘化N-正丁基氟哌啶醇(F2)2.0 mg·kg^-1后采集血样,用高效液相色谱-质谱(HPLC-MS)联用技术测定血浆药物浓度,并用3p97 软件拟合计算药代动力学参数。结果和结论: 兔耳缘静脉给药后的血药浓度-时间曲线符合二室开放模型,其主要药动学参数为:分布半衰期T_12α是0.10 h,消除半衰期Σ_12β 是6.4 h,曲线下面积AUC 为183 μg·h^-1·L^-1,中央室分布容积VC 为4 L,清除率Cl 为12.9 L·h^-1。HPLC-MS 联用方法测定F2 血药浓度,灵敏度高,专属性强。     

灯盏花素在小鼠体内药物动力学研究

目的:研究灯盏花素在小鼠体内的药物动力学和绝对生物利用度。方法:采用固相萃取-高效液相色谱(SPE-HPLC)法, 测定小鼠静脉注射灯盏花素50 mg°kg^-1和灌胃150 mg°kg^-1后血浆灯盏乙素浓度, 3p97 程序处理数据。结果:小鼠静注灯盏花素后灯盏乙素的血浓-时间变化符合三房室模型,AUC、C₀ 和T_1/2β 分别为12.97±3.55 mg°L^-1 °h、132.23±39.90 mg°L^-1 和4.04±1.29 h。灌胃后药物吸收很快, 但血浓低。采用非房室模型法计算AUC 为1.97±0.53 mg°L^-1°h, T_1/2Ke 为3.41±1.23 h。绝对生物利用度为5.05%。结论:灯盏花素经静注在小鼠体内的药代动力学符合三室模型。灌胃给药吸收快, 但吸收差, 绝对生物利用度低, 且药时曲线变化不规则。     

盐酸曲马多分散片人体药物动力学及相对生物利用度

目的 研究国产盐酸曲马多分散片的人体药代动力学参数和生物等效性。方法 12名健康受试者交叉口服国产盐酸曲马多分散片100mg 和进口盐酸曲马多胶囊100mg, 用HPLC法测定血浆中药物浓度。结果 两种制剂的 血药浓度曲线均符合二室模型,T_1/2分别为(7.69+3.74)h和(7.66+3.41)h,血药浓度曲线下面积分别为(3100土1165)μg·h·^-1和(3212土1260)μug·h·L^-1,两种制剂的药代动力学参数均无显著性差异(P>0.05)。结论 两种制剂的口服生物利用度具有生物等效性。     

国产双氯芬酸钠缓释栓的人体药代动力学研究

目的:研究国产双氯芬酸钠缓释栓人体内的药代动力学特征。方法:20 名健康志愿者单剂量给予100 mg 双氯芬酸钠缓释栓, 采用反相高效液相色谱法测定血浆中双氯芬酸钠的浓度。用3p87 程序计算其药代动力学参数。结果:主要药代动力学参数C_max 为1.1 ±0.3 mg·L^-1;T_max 为1.7 ±0.7 h;T_1/2(ke) 为2.4 ±0.6 h;CL 为27 ±6 L·h^-1;V_d 为74 ±25 L;AUC_0-∞为4.0 ±1.2 mg·h^-1·L^-1 。结论:双氯芬酸钠缓释栓在健康人体内的药代动力学符合单室模型特征。     

环丙沙星对美吡达的药代学和药效学的影响

目的 研究美吡达与环丙沙星联合应用时环丙沙星对美吡达药代动力学及药效学的影响。方法 糖尿病大鼠24 只分为联合用药组(环丙沙星+美吡达)及单独用药组(美吡达),治疗9 d 后分别测定两组美吡达血药浓度并计算药代动力学参数及血糖。结果 两组大鼠美吡达的药代动力学过程均符合一房室模型。且联合用药组美吡达血药浓度显著升高,清除率下降50%(P<0.05),吸收半衰期延长63.7 %(P<0.05),单独应用美吡达治疗后血糖为5.978 mmol·L^-1,联合应用环丙沙星治疗后血糖为5.301 mmol·L^-1;两组降糖效果差异具有显著性。结论 环丙沙星对美吡达的吸收药代动力学有影响,美吡达联合应用环丙沙星降糖效果比单独应用美吡达时强。故同时给药时应注意调整美吡达的用药剂量以保证用药安全。     

两种扑热息痛薄膜包衣异型片的药代动力学比较及生物利用度初步研究

目的 研究单剂量口服两种扑热息痛异型片500mg的药代动力学和相对生物利用度。方法 10名男性健康志愿者按照随机、交叉试验设计,采集服药后0.5,1,1.5,2,3,4,6,8,10h的血样本。用HPLC方法测定扑热息痛的血药浓度。结果 两种制剂的药-时曲线符合口服吸收有滞后时间的一级动力学一室模型。受试制剂扑热息痛薄膜包衣异型片(康司达)的主要药代动力学参数:C_max=5.51±1.24mg/L,T_peak=1.03±0.43h,T_1/2ka=0.27±0.16h,T_1/2ke=2.60±0.51h,AUC_0~t=23.69±4.08mg/h·L^-1,MRT=3.65±0.22h。结论 受试制剂相对于参比制剂的生物利用度为102.5±13.3%,受试制剂(康司达)与参比制剂扑热息痛片生物等效。     

高效液相-质谱联用法(HPLC-MS) 测定灯盏乙素血药浓度及其临床药代动力学研究

目的:研究灯盏花素片在中国人体内的药代动力学。方法:20 名健康志愿者单剂量口服120 mg灯盏花素片, 用高效液相-质谱联用法测定血浆中灯盏乙素总苷元。结果:本实验建立的血药浓度测定方法, 血浆中杂质不干扰样品的测定, 线性范围为0.0126～3.24 mg°L^-1;日内和日间精密度均小于12.0%。20 名健康受试者单剂量口服灯盏花素片(120 mg) 后, 主要药代动力学参数:T_max=7.0±2.3 h、C_max=0.9±0.5 mg°L^-1、AUC_0-tn=5.6±1.6mg°h°L^-1、AUC_0-∞=5.8±1.6 mg°h°L^-1、MRT_0-tn=8.0±1.1 h、MRT_0-∞=8.6±1.4 h。结论:建立的LC-MS 法适用于灯盏乙素人体药代动力学研究。灯盏花素片口服药代动力学特点是达峰时间较长, 约占受试者总人数45% 的药时曲线有双峰现象。     

冻干重组胰高血糖素样肽-1受体激动剂在中国健康成年受试者中皮下给药药代动力学研究

目的: 评价冻干重组胰高血糖素样肽-1受体激动剂在中国健康成年受试者中皮下单、多次给药的药代动力学特征。方法: 研究纳入12名符合入选标准的健康成人受试者,男女各半。给药第1～8日,每日皮下注射 5 μg 的rE-4一次,连续8日。结果: 受试者第1日和第8日皮下注射rE-4后的药代动力学参数AUC_0-t分别为 690.2、718.0 ng·h·L^-1;AUC_0-∞分别为 779.8、797.9 ng·h·L^-1;t_max分别为 0.89、0.79 h;C_max分别为 201.4、212.7 ng/L;t_1/2Z分别为 2.38、2.31 h;CLz/F分别为 6.7、6.5 L/h。单、多次给药主要药代动力学参数差异无统计学意义,多次给药后累积指数为 1.0017。试验期间无严重不良事件,仅发生1例轻度不良反应。结论: 中国健康受试者每日1次连续8日皮下注射 5 μg rE-4安全性良好,药时曲线符合一室模型,体内无蓄积,可推荐进一步用于II期临床研究。     

纳米红色元素硒在Beagle 犬的药代动力学分析

目的 观察纳米红色元素硒(Nse) 在Beagle 犬的药代动力学特点。 方法 催化荧光法测定用药前基线值和用药后不同时间血硒浓度, 分别用血硒实测值和上升值计算药动学参数。 结果 Nse 代谢符合一室模型, 吸收较快, 药峰值为155 mg·L^-1 (实测值) 和135.4 mg·L^-1 (上升值), 达峰时间约为2 h,但消除较慢, 清除率极低, t12 长达34.6 h(实测值)和20 h(上升值)。 结论 长时间、大剂量服用Nse 可能导致药物蓄积;体内具有基线值时, 计算药动学参数宜用变化值, 不宜用实测值。     

注射用纳米羟基喜树碱与普通粉针在家兔体内的药代动力学比较研究

目的:考察注射用纳米羟基喜树碱静脉推注给药后, 家兔血浆药物浓度随时间变化趋势和药代动力学参数, 并与注射用羟基喜树碱进行比较, 评价纳米针药动学特性。方法:建立HPLC 检测家兔血浆中羟基喜树碱含量的方法, 采用3p97 药代动力学计算软件模拟房室模型并计算药代动力学参数。结果:注射用羟基喜树碱家兔耳静脉单次推注给药符合1/C² 权重的二室模型, 而注射用纳米羟基喜树碱符合1/C² 权重的三室模型。注射用羟基喜树碱的血浆C_max 是同剂量纳米针的3 倍, AUC 也是纳米针的2～3 倍。同剂量下HCPT 纳米针组Vc 均大于粉针组。纳米针消除半衰期(T_1/2β) 较冻干粉针延长。结论:注射用纳米羟基喜树碱在家兔体内的药动学特性与普通粉针比较发生显著变化。     

Effects of Post-weld Heat Treatment on Microstructure,Mechanical Properties and the Role of Weld Reinforcement in 2219 Aluminum Alloy TIG-Welded Joints

In as-welded state, each region of 2219 aluminum alloy TIG-welded joint shows diff erent microstructure and microhardness due to the diff erent welding heat cycles and the resulting evolution of second phases. After the post-weld heat treatment, both the amount and the size of the eutectic structure or θ phases decreased. Correspondingly, both the Cu content in α-Al matrix and the microhardness increased to a similar level in each region of the joint, and the tensile strength of the entire joint was greatly improved. Post-weld heat treatment played the role of solid solution strengthening and aging strengthening. After the post-weld heat treatment, the weld performance became similar to other regions, but weld reinforcements lost their reinforcing eff ect on the weld and their existence was more of an adverse eff ect. The joint without weld reinforcements after the post-weld heat treatment had the optimal tensile properties, and the specimens randomly crack in the weld zone.     

The First Phase of the SRIF Industrialized Base in ＂West Area＂ Has Been Put into Operation

After nearly two years＇ tense construction, the first phase of industrialized base of Shenyang Research Institute of Foundry （SRIF）, located at the Tiexi Casting and Forging Industrial Park in the west of Tiexi District, has now been completed and formally put into operation.     

THERMODYNAMICS STUDY ON THE DECOMPOSITION OF CHROMITE WITH KOH

Institute of Process Engineering, Chinese Academy of Sciences, China, has proposed a method for oxidative leaching of chromite with potassium hydroxide. Understanding the mechanism of chromite decomposition, especially in the potassium hydroxide fusion, is important for the optimization of the operating parameters of the oxidative leaching process. A traditional thermodynamic method is proposed and the thermal decomposition and the reaction decomposition during the oxidative leaching of chromite with KOH and oxygen is discussed, which suggests that chromite is mainly destroyed by reactions with KOH and oxygen. Meanwhile, equilibrium of the main reactions of the above process was calculated at different temperatures and oxygen partial pressures. The stable zones of productions, namely, K2CrO4 and Fe2O3, increase with the decrease of temperature, which indicates that higher temperature is not beneficial to thermodynamic reactions. In addition, a comparison of the general alkali methods is carried out, and it is concluded that the KOH leaching process is thermodynamically superior to the conventional chromate production process.     

INFLUENCE OF HEAT TREATMENT ON DAMPING BEHAVIOUR OF THE MAGNESIUM WROUGHT ALLOY AZ61

The effect of isochronal heat treatments for 1h on variation of damping, hardness and microstructural change of the magnesium wrought alloy AZ61 was investigated. Damping and hardness behaviour could be attributed to the evolution of precipitation process. The influence of precipitation on damping behaviour was explained in the framework of the dislocation string model of Granato and Lücke.     

新型的治疗阿尔茨海默氏症药物(1-二甲基磷酰基-2,2,2-三氯)-乙基-1-醇烟酸醋对体外神经细胞的作用

目的: 观察本实验室合成的一种治疗阿尔茨海默氏症(AD)的药物(1-二甲基磷酰基-2, 2, 2 -三氯)-乙基^-1-醇烟酸醋(NMF),对体外培养的皮层神经细胞活性的影响以及对海人藻酸(KA)所致的神经损伤的保护作用。方法: 采用体外培养皮层神经元的方法,解剖分离 15 d胚胎小鼠皮层神经细胞, 接种于 96孔板,48 h 后加药并培养 72 h,以 MIT 法 观察 NMF 对小鼠皮层神经细胞活性的影响;同时将接种于 24 孔板的细胞预先给予 NMF,d 3 时加或不加KA处理后,以台盼蓝染色鉴别并计数死、活细胞,可得出细胞的存活率。结果: NMF 明显促进胎鼠皮层神经元活性,其中 NMF1、0. 1、10nmol·L^-1促进神经元活性增殖率分别高达 34.7%、37.4%、36. 7%, NMF 明显促进正常胎鼠皮层神经元存活卒,与对照组比较,10nmol·L^-1 NMF 对皮层神经元的存活率分别提高 39.3%、73.5%。 NMF能显著 对抗 KA 所致的神经元损伤,与 KA 损伤组相比, NMF0.1、10、10nmol·L^-1对损伤皮层神经元的保护率分别为 77.30%、80.10%、84.15%。结论: NMF 明 显促进胎鼠皮层神经元的洁性、提高正常皮层神经元,的存活卒,并能有效地保护KA所致的神经元损伤,提示 NMF 是一种很有潜力的治疗 AD 的药物。     

Effect of Rare Earth Doping on Impedance,Modulus and Conductivity Properties of Multiferroic Composites:0.5(BiLa_xFe_(1-x)O_3)–0.5(PbTiO_3)

The Lanthanum-doped bismuth ferrite–lead titanate compositions of 0.5(Bi LaxFe1-xO3)–0.5(Pb Ti O3)(x = 0.05,0.10,0.15,0.20)(BLxF1-x-PT) were prepared by mixed oxide method.Structural characterization was performed by X-ray diffraction and shows a tetragonal structure at room temperature.The lattice parameter c/a ratio decreases with increasing of La(x = 0.05–0.20) concentration of the composites.The effect of charge carrier/ion hopping mechanism,conductivity,relaxation process and impedance parameters was studied using an impedance analyzer in a wide frequency range(102–106Hz) at different temperatures.The nature of Nyquist plot confirms the presence of bulk effects only,and non-Debye type of relaxation processes occurs in the composites.The electrical modulus exhibits an important role of the hopping mechanism in the electrical transport process of the materials.The ac conductivity and dc conductivity of the materials were studied,and the activation energy found to be 0.81,0.77,0.76 and 0.74 e V for all compositions of x = 0.05–0.20 at different temperatures(200–300 °C).     

Three-Dimensional Growth of Coherent Ferrite in Austenite: A Molecular Dynamics Study

Coherent second phase often exhibits anisotropic morphology with specifi c orientations with respect to both the second and the matrix phases. As a key feature of microstructure, the morphology of the coherent particles is essential for understanding the second-phase strengthening eff ect in various industrial alloys. This letter reports anisotropic growth of coherent ferrite from austenite matrix in pure iron based on molecular dynamics simulation. We found that the ferrite grain tends to grow into an elongated plate-like shape, independent of its initial confi guration. The fi nal shape of the ferrite is closely related to the misfi t between the two phases, with the longest direction and the broad facet of the plate being, respectively, consistent with the best matching direction and the best matching plane calculated via the Burgers vector content(BVC) method. The strain energy calculation in the framework of Eshelby's inclusion theory verifi es that the simulated orientation of the coherent ferrite is energetically favorable. It is anticipated that the BVC method will be applicable in analysis of anisotropic growth and morphology of coherent second phase in other phase transformation systems.     

Using Finite Element and Contour Method to Evaluate Residual Stress in Thick Ti-6Al-4V Alloy Welded by Electron Beam Welding

This work was to reveal the residual stress profile in electron beam welded Ti-6Al-4V alloy plates(50 mm thick) by using finite element and contour measurement methods.A three-dimensional finite element model of 50-mmthick titanium component was proposed,in which a column–cone combined heat source model was used to simulate the temperature field and a thermo-elastic–plastic model to analyze residual stress in a weld joint based on ABAQUS software.Considering the uncertainty of welding simulation,the computation was calibrated by experimental data of contour measurement method.Both test and simulated results show that residual stresses on the surface and inside the weld zone are significantly different and present a narrow and large gradient feature in the weld joint.The peak tensile stress exceeds the yield strength of base materials inside weld,which are distinctly different from residual stress of the thin Ti-6Al-4V alloy plates presented in references before.     

Microstructures and Tensile Properties of Ultrafine-Grained Ni–(1–3.5) wt% SiC_(NP) Composites Prepared by a Powder Metallurgy Route

Silicon carbide nanoparticle-reinforced nickel-based composites(Ni–Si CNP),with a Si CNPcontent ranged from1 to 3.5 wt%,were prepared using mechanical alloying and spark plasma sintering.In addition,unreinforced pure nickel samples were also prepared for comparative purposes.To characterize the microstructural properties of both the unreinforced pure nickel and the Ni–Si CNPcomposites transmission electron microscopy(TEM) was used,while their mechanical behavior was investigated using the Vickers pyramid method for hardness measurements and a universal tensile testing machine for tensile tests.TEM results showed an array of dislocation lines decorated in the sintered pure nickel sample,whereas,for the Ni–Si CNPcomposites,the presence of nano-dispersed Si CNPand twinning crystals was observed.These homogeneously distributed Si CNPwere found located either within the matrix,between twins or on grain boundaries.For the Ni–Si CNPcomposites,coerced coarsening of the Si CNPassembly occurred with increasing Si CNPcontent.Furthermore,the grain sizes of the Ni–Si CNPcomposites were much finer than that of the unreinforced pure nickel,which was considered to be due to the composite ball milling process.In all cases,the Ni–Si CNPcomposites showed higher strengths and hardness values than the unreinforced pure nickel,likely due to a combination of dispersion strengthening(Orowan effects) and particle strengthening(Hall–Petch effects).For the Ni–Si CNPcomposites,the strength increased initially and then decreased as a function of Si CNPcontent,whereas their elongation percentages decreased linearly.Compared to all materials tested,the Ni–Si CNPcomposite containing 1.5% Si C was found more superior considering both their strength and plastic properties.     

Directional Growth of Tin Crystals Controlled by Combined Solute Concentration Gradient Field and Static Magnetic Field

A new method was introduced to achieve directional growth of Sn crystals. Microstructures in liquid(Pb)/liquid(Sn) diffusion couples were investigated under various static magnetic fields. Results show that the β-Sn crystals mainly reveal an irregular dendritic morphology without or with a relatively low static magnetic field(B0.3 T). When the magnetic field is increased to 0.5 T, the β-Sn dendrites close to the final stage of growth begin to show some directional character. With a further increase in the magnetic field to a higher level(0.8–5 T), the β-Sn dendrites have an enhanced directional growth character, but the dendrites show a certain deflection. As the magnetic field is increased to 12 T, the directional growth of the β-Sn dendrites in the center of the couple is severely destroyed. The mechanism of the directional growth of the β-Sn crystals and the deflection of the β-Sn crystals with the application of static magnetic field was tentatively discussed.