用统计学方法优化硝苯地平脂质体处方

采用乙醚注入法制备硝苯地平脂质体,在单因素实验基础上用Box-Behnken设计实验,并用统计学方法考察磷脂量、脂药比和胆固醇磷脂比对脂质体包封率的影响.结果表明:多元二次回归模型最优处方制备的硝苯地平脂质体平均包封率为86.54%;人工神经网络模型结合遗传算法最优处方制备的硝苯地平脂质体平均包封率为97.25%;与二次回归模型相比,人工神经网络模型更适于优化硝苯地平脂质体的制备.优化后得到最佳制备处方为:磷脂量612.4mg,脂药比为60.02,磷脂胆固醇比为6.401.     

甲巯咪唑脂质体的制备及其对大鼠T_3、T_4及TSH值的影响

目的制备甲巯咪唑脂质体并测定其包封率,考察其对大鼠T_3、T_4及TSH值的影响。方法应用逆向蒸发-超声法制备甲巯咪唑脂质体,透射电子显微镜考察其形态与粒径;采用高效液相色谱法测定脂质体的包封率;将大鼠随机分成2组,分别服用甲巯咪唑片剂和脂质体溶液,8周后测定大鼠血清T_3、T_4及TSH值。结果制备的脂质体粒径大小均匀,粒径范围为150～175nm;甲巯咪唑检测浓度的线性范围为0.01～1mg·mL~(-1)(r=0.9991,n=6),平均回收率为100.03%(RSD=1.24%,n=6);包封率最高可达75.8%,最低42.4%;脂质体溶液给药与口服给药两组比较,脂质体溶液给药对大鼠血清T_3、T_4有显著抑制作用,P0.05;对TSH的影响两组间无显著性差异。结论本方法制备的甲巯咪唑脂质体可以在临床上推广使用。     

醉椒素脂质体的制备及其理化性质考察

制备醉椒素脂质体并对其稳定性进行考察.采用薄膜-超声分散法制备脂质体,利用高效液相色谱法测定其主药含量,并考察其粒径、Zeta电位、包封率等指标及在室温与4℃保存14 d的稳定性.所得脂质体粒径小而均匀,粒径均值为(161±5)nm,Zeta电位为(2.37 ±0.2) mV,包封率均在77.09％以上,稳定性考察各项指标均无明显改变.由此可以得出结论,所制制剂包封率较高,稳定性良好.     

溶菌酶脂质体的制备工艺

研究了溶菌酶脂质体的制备工艺,确定了具有较高包封率的工艺条件。采用逆相蒸发法,考察了溶剂密度、膜材浓度、制备温度和超声时间等因素对溶菌酶脂质体包封率、稳定性及形态学的影响。研究结果表明:0.6 g卵磷脂和0.3 g胆固醇加入到12 mL密度为1 g/mL的混合有机溶剂中,37°C下用逆相蒸发法制备溶菌酶脂质体,并对其进行1.5 m in超声后所得产品包封率可达84%以上,所得脂质体形态圆整,粒径为150~400 nm,在4°C下保存40 d外观无明显变化。     

聚乙二醇修饰白藜芦醇脂质体的特性及其抗肿瘤实验研究

为了探索聚乙二醇(PEG)修饰白藜芦醇(resveratrol,RES)脂质体对提高RES脂质体稳定性、药物包封率和抗肿瘤活性的有效性,通过声波水合法设计的正交实验确定了最高药物包封率的RES脂质体中卵磷脂与胆固醇的摩尔比为3∶1,卵磷脂与白藜芦醇的摩尔比为3∶1,该条件下样品经PEG-2000修饰后仍能保持300 nm左右的大小,6 d后仍具有较高的包封率。此外,以人白血病K562细胞为例对PEG修饰白藜芦醇脂质体(PEG-RES-LIP)的抗肿瘤活性进行了验证。实验表明,PEG-RES-LIP对K562细胞的最佳药物浓度和作用时间分别为120μg/mL和48 h,最高抑制率为85.9%±1.9%,RES-LIP对K562细胞的最高抑制率为67.3%±2.3%。研究结果表明,用聚乙二醇修饰RES脂质体可以有效提高RES脂质体的稳定性、药物包封率和抗肿瘤活性,从而提供了一种可以有效维持其稳定性和抗肿瘤活性的RES脂质体制备方法。     

响应面法优化龙胆苦苷脂质体的复乳法制备工艺

采用复乳法制备脂质体,使用3因素3水平的Box-Behnken响应面设计,以脂质体的包封率、载药量和综合评价为响应值,考察龙胆苦苷药液质量浓度、第一次乳化超声时间及膜材中磷脂与胆固醇的质量比对响应值的影响,并用Design-Expert 7.1.3软件（试用版）进行数据拟合、数学建模和预测分析。优化出的龙胆苦苷脂质体的最佳处方为龙胆苦苷药液质量浓度为2.04 mg/mL、第一次乳化超声时间为7.07 min、脂质体膜材中胆固醇与磷脂质量比为0.45。研究结果表明,在最优处方下龙胆苦苷脂质体形态完整、状态稳定,平均粒径为131 nm,其包封率为52.39%,与预测值的偏差率小于1%。     

更昔洛韦脂质体的制备及稳定性考察

采用逆相蒸发法制备更昔洛韦脂质体,同时对所制脂质体进行了表征和稳定性分析.采用透射电镜观察其形态;采用激光粒度仪测定平均粒径;用葡聚糖凝胶层析柱分离含药脂质体和游离药物并测定包封率;用离心加速试验及室温冷藏法考察脂质体的稳定性.结果表明,得到的更昔洛韦脂质体的平均粒径为332.3 nm,多相分散系数为0.143,包封率为43.24%,在考察时间段内,所制脂质体稳定性良好.     

氟比洛芬脂质体的制备及其载药性能研究

利用薄膜蒸发-超声分散法制备氟比洛芬脂质体,通过鱼精蛋白凝聚法测定脂质体对氟比洛芬的包封率和载药率,研究了氟比洛芬脂质体载药性能的影响因素.结果表明,制得的氟比洛芬脂质体的粒径为100～250 nm,具有良好的分散性;氟比洛芬定位于脂质体的疏水基团区域,它在卵磷脂相和水相中的分配系数KD为815.6.当卵磷脂浓度为5.4×10-4mol.L-1时,所得脂质体对氟比洛芬的包封率和载药率比较理想;随着氟比洛芬与卵磷脂的质量比的增加,脂质体对氟比洛芬的载药率增大,包封率降低;胆固醇可以调节脂质体膜的稳定性,胆固醇与卵磷脂的质量比应该控制在0.3以下,过高浓度的胆固醇会大量插入膜内使得膜的刚性增强,导致脂质体对氟比洛芬的载药率和包封率降低.     

青蒿素脂质体的制备及性能研究

目的:通过对青蒿素脂质体的处方和制备工艺研究,研制高包封率和稳定的脂质体。方法:采用乙醇注入法制备脂质体,以正交实验优化处方,测定了脂质体中药物的包封率,并初步考察了脂质体的稳定性。结果:优化处方与工艺所得脂质体形态均匀,包封率大于85%,载药量达27.22%,粒径约为90 nm,Zeta电位约为-68.4 mV,具有良好的稳定性。结论:乙醇注入法制备脂质体工艺简便,包封率高,制备的脂质体稳定好。     

泛昔洛韦与阿昔洛韦治疗生殖器疱疹58例观察

目的 :评价泛昔洛韦在复发性生殖器疱疹治疗中的疗效和不良反应。方法 :5 8例复发性生殖器疱疹随机分成两组 ,一组用泛昔洛韦片 2 5 0mg ,每日 3次 ,连续 7d。另一组用阿昔洛韦片 2 0 0mg ,每日 5次 ,连续 7d。结果 :两组痊愈率分别为 86 .7%、75 .0 % ,有效率分别为 10 0 %和 96 .4 %。用泛昔洛韦痊愈时间为 (4 7± 1 8)d ,阿昔洛韦为 (5 2± 1 1)d(P <0 0 5 )。结论 :泛昔洛韦治疗生殖器疱疹具有用药剂量小、次数少、起效快、痊愈时间短的特点 ,可作为治疗生殖器疱疹的首选药物     

Influence of site-directed mutation of cytochrome b5 Phe35 on the protein’s structure and properties

Kinetic studies of the heme dissociation from the wild type and Phe35Tyr, Phe35Leu mutants of bovine liver microsomal ferricytochrome b 5 indicate that the oxidized Phe35Tyr mutant is more stable towards denaturant than wild type but Phe35Leu mutant proceeded with a different mechanism compared with wild type cytochrome b 5 and Phe35Tyr mutant protein. Because of the decrease of side chain volume in Phe35Leu mutant, a cavity produced in the interior of the protein may offer a channel for urea molecule to enter the hydrophobic pocket. When urea concentration is larger than 5 mol/L, the urea molecule may compete to coordinate the iron of heme with His39, that results in sharp increase of the rate of heme dissociation. The interaction between cytochrome b 5 and cytochrom c demonstrated that a 1:1 protein complex was formed between the two proteins. The binding constants of cytochrome b 5 with cytochrome c are: wild type K A=4.2(±0.01)×10 6(mol/L) -1 , Phe35Tyr K A=3.7(±0.01)×10 6(mol/L) -1 and Phe35Leu K A=4.7(±0.01)×10 6(mol/L) -1 respectively ( I =1 m mol/L, pH 7.0 soldium phosphate buffer, 25℃). These results clearly show that the mutation at Phe35 has no influence on the binding of cytochrome b 5 with cytochrome c and that the hydrophilic patch residues are not involved in the binding of cytochrome b 5 and cytochrome c.     

利多卡因凝胶治疗带状疱疹后神经痛临床疗效分析

目的探讨利多卡因凝胶治疗带状疱疹后神经痛的临床疗效.方法随机将86例带状疱疹后神经痛患者分为两组,对照组43例使用双氯芬酸凝胶治疗,治疗组43例使用利多卡因凝胶治疗,观察比较两组临床疗效.结果观察组治疗总有效率(93.02%)显著优于对照组(76.74%)(P0.05);治疗前,两组患者VAS评分无统计学意义(P0.05);治疗后1,2,4周观察组VAS评分(13.5±14.2),(18.5±17.1),(20.8±19.0)分,均显著优于对照组(6.8±12.5),(7.3±12.4),(8.2±14.3)分,差异具有统计学意义(P0.05).结论利多卡因凝胶治疗带状疱疹后神经痛,效果明显,值得进一步深入研究与临床推广使用.     

组织胺对大鼠DRG神经元ATP-激活电流的抑制作用

目的:探讨组织胺对大鼠DRG神经元ATP-激活电流的调制作用.方法:采用全细胞膜片钳技术,在新鲜分离的大鼠背根神经节细胞上进行.结果:实验观察到组织胺在DRG神经元可引起内向电流,并有明显的浓度依赖性.在被检测的DRG神经元中,85%(30/35)的细胞对ATP敏感,可引起一浓度依赖性的去敏感的内向电流.预加10-8、10-7、10-6、10-5、10-4mol/L组织胺后,对ATP-激活电流的抑制分别是:(12.50±3.2%(n=5)、(24.49±3.5%(n=5)、(35.18±4.5%(n=6)、(32.62±5.8%(n=8)、(23.53±4.2%(n=5),呈浓度依赖性.结论:组织胺对大鼠DRG神经元ATP-激活电流有明显的抑制作用.     

In situ simultaneous determination of trace elements, U-Pb and Lu-Hf isotopes in zircon and baddeleyite

This paper describes a combined method of simultaneously measuring U-Pb and Lu-Hf isotopes as well as trace elements in Phalaborwa baddeleyite and 91500, GJ-1, TEMORA-1 and SK10-2 zircons by means of Neptune MC-ICPMS and Agilent Q-ICPMS connected to a 193 nm excimer laser ablation system. Material ablated by laser was carried in different proportions into Q-ICPMS for U-Pb isotopic and trace elemental and MC-ICPMS for Lu-Hf isotopic compositions. Experiments indicate that different proportions of ablated material for the Q-ICPMS and MC-ICPMS （6：4, 5：5 and 4：6 respectively） do not show any bias for the zircon/baddeleyite U-Pb age, Lu-Hf isotope and trace elemental compositions within analytical errors. Using 40-60 μm spot size, the obtained U-Pb ages of Phalaborwa baddeleyite, 91500, GJ-1, TEMORA and SK10-2 zircons are 2065±15 （2σ, n=20）, 1063±6 （2σ, n=-19）, 613±6 （2σ, n=20）, 416±5 （2σ, n=20） and 32.6±0.5 （2σ, n=20） Ma, respectively. The ^176Hf/^177Hf ratios are 0.281231±24 （2SD, n=20）, 0.282310±35 （2SD, n=19）, 0.282028±34 （2SD, n=20）, 0.282687±34 （2SD, n=20） and 0.282752±53 （2SD, n=20）, respectively. The obtained trace elemental compositions are identical to the reference values. Therefore, this kind of technique makes it possible to simultaneously obtain the U-Pb age, Lu-Hf isotopes and trace elemental compositions of zircon and baddeleyite, which could be an important tool in solving problems in earth sciences.     

The v-v energy transfer of highly vibrationally excited states (I)──Vibrational quenching of CO(v) by CO_2

The relaxation of the highly vibrationally excited CO (v=1-8) by CO\-2 is studied by time_resolved Fourier transform infrared emission spectroscopy (TR FTIR). 193 nm laser photolysis of the mixture of CHBr\-3 with O\-2 generates the highly vibrationally excited CO(v) molecules. TR FTIR records the intense infrared emission of CO(v→v-1). The vibrational populations of each level of CO(v) have been determined by the method of spectral simulation. Based on the evolution of the time resolved populations and the differential method, 8 energy transfer rate constants of CO(v=1-8) to CO 2 molecules are obtained: (5.7±0.1), (5.9±0.1), (5.2±0.2), (3.4±0.2), (2.4±0.3), (2.2±0.4), (2.0±0.4) and (1.8±0.6) (10 -14 cm 3·molecule -1·s -1), respectively. A two_channel energy transfer model can explain the feature of the quenching of CO(v) by CO 2. For the lower vibrational states of CO, the vibrational energy transfers preferentially to the υ\-3 mode of CO 2. For the higher levels, the major quenching channel changes to the vibrational energy exchange between CO(v→v-1) and the υ\-1 mode of CO 2.     

消化道穿孔围手术期液体治疗中的正平衡

目的 :探讨消化道穿孔 (DTP)急诊手术病例围手术期液体正平衡与APACHEⅡ评分的关系。方法 :根据APACHEⅡ评分 ,将连续 3 72例DTP病例分为轻症 ( <8分 )、重症 ( 8～ 19分 )和危重病例 (≥ 2 0分 ) 3组 ,比较 3组病例手术前、手术日和术后第 1日的液体正平衡量。结果 :轻症、重症和危重病例术前的液体正平衡量分别为 112 6.91± 414.80mL、2 3 60 .89± 85 7.0 3mL和 3 494.97± 995 .65mL(P <0 .0 1) ;手术日液体正平衡量分别为 2 10 3 .71± 72 8.99mL、40 5 0 .5 6± 10 3 6.3 7mL和 5 743 .95± 12 5 6.2 1mL(P <0 .0 1) ;术后第 1日液体正平衡量分别为 916.81± 5 5 9.62mL、12 11.43± 679.85mL和 15 87.0 9± 73 3 .3 8mL(P <0 .0 1)。结论 :无论是术前、手术当日或术后第 1日 ,DTP病例的液体正平衡量与其APACHEⅡ评分正相关。APACHEⅡ评分可估测DTP病例的液体正平衡量 ,指导其围手术期的液体治疗     

Geochemistry and zircon U-Pb ages of granulite xenolith from Tuoyun basalts, Xinjiang： Implications for the petrogenesis and the lower crustal nature beneath the southwestern Tianshan

The continental lithosphere growth mainly includes the horizontal accretion at the plate boundaries and vertical accretion within the plate[1]. Mafic magmatic materials, as the products of crust-mantle interaction[2,3], became more and more important in studying the formation and evolu- tion of the lower crust. The previous geologic researcheson Tianshan, extending nearly 2500 km from east to west, and the neighbor area were mainly focused on the Paleozoic collision structure[4 ― 6], Mesozoi…     

The v-v energy transfer of highly vibrationally excited states (I)

The relaxation of the highly vibrationally excited CO (v = 1–8) by CO₂ is studied by timeresolved Fourier transform infrared emission spectroscopy (TR FTIR). 193 nm laser photolysis of the mixture of CHBr₃ with O₂ generates the highly vibrationally excited CO(v) molecules. TR FTIR records the intense infrared emission of CO(v→v-1). The vibrational populations of each level of CO(v) have been determined by the method of spectral simulation. Based on the evolution of the time resolved populations and the differential method, 8 energy transfer rate constants of CO(v = 1–8) to CO₂ molecules areobtained: (5.7±0.1), (5.9±0.1), (5.2±0.2), (3.4±0.2), (2.4±0.3), (2.2±0.4), (2.0±0.4) and (1.8±0.6) (10¹⁴ cm³ · molecule⁻¹ · s⁻¹), respectively. A two-channel energy transfer model can explain the feature of the quenching of CO(v) by CO². For the lower vibrational states of CO, the vibrational energy transfers preferentially to the u³ mode of CO² For the higher levels, the major quenching channel changes to the vibrational energy exchange between CO(v→v-1) and the u¹ mode of CO².     

巨峰葡萄胚培养技术的研究

选用巨峰葡萄在花后35～60 d,取其胚接种在含有GA3I、AA、6-BA的不同激素水平MS培养基上进行胚挽救,以研究葡萄的幼胚培养技术.结果表明,巨峰葡萄在花后60 d效果最好.在附加GA30.5 mg/LI、AA1.0 mg/L、6-BA0.5 mg/L的最佳培养基上得到了(76.0±16.7)%的发育率和(69.1±13.1)%的成苗率.     

The v-v energy transfer of highly vibrationally excitedstates (Ⅱ)──Vibrational quenching of CO(v) by H_2O

The vibrational energy transfer from highly vibrationally excited CO to H 2O molecules is studied by time-resolved Fourier transform infrared emission spectroscopy (TR FTIR). Following the 193 nm laser photolysis of CHBr 3 and O 2 the secondary reactions generate CO(v). The infrared emission of CO(v→v-1) is detected by TR FTIR. The excitation of H 2O molecules is not observed. By the method of the spectral simulation and the differential technique, 8 rate constants for CO(v)/H 2O system are obtained: (1.7±0.1), (3.4±0.2), (6.2±0.4), (8.0±1.0), (9.0±2.0), (12±3), (16±4) and (18±7) (10 -13cm 3·molecule -1·s -1). At least two reasons lead to the efficient energy transfer. One is the contributions of the rotational energy to the vibational energy defect and the other is the result of the complex collision. With the SSH and ab initio calculations, the quenching mechanism of CO(v) by H 2O is suggested.