冻干人硬脑膜用于修补硬脑膜缺损和血管内栓塞治疗的临床观察

目的：探讨用冻干人硬脑膜行硬脑膜成硬脊膜缺损修补和血管内栓塞治疗的效果。方法：用冻干人硬脑膜修补因脑肿瘤、脑外伤、脊髓内肿瘤手术引起的硬脑膜或硬脊膜缺损,并不同规格的的冻干人硬脑膜微粒或微丝行靶血管栓塞。结果：（１）冻干人硬脑膜用于硬脑或硬脊膜缺损修补患者２２９例,无颅仙感染等并发症,用于血管内栓塞靶血管２８例,可明显减少或闭塞颅内肿瘤的血供。结论：冻干人厝脑膜是一种较为理想的硬脑膜缺损修补和血管     

海生素冻干粉的质量控制及HPLC指纹图谱研究

目的 建立海生素冻干粉的质量控制方法及其高效液相指纹图谱。方法 用茚三酮反应和双缩脲反应对海生素冻干粉进行鉴别；用氮测定法测定海生素冻干粉中的氮含量，并用高效液相色谱法建立海生素冻干粉的高效液相指纹图谱。结果 茚三酮反应和双缩脲反应呈阳性，海生素冻干粉中氮含量不低于6．0％，且各批次间样品的指纹图谱一致，冻干粉质量稳定。结论 建立的方法分析快速、准确，可用于该制剂的质量控制。     

复方双黄连粉针剂金银花中间体化学成分研究

目的:对复方双黄连粉针剂中配剂金银花中间体的化学成分进行系统分离和鉴定,以寻找引起不良反应的物质基础.方法:采用柱色谱以及制备型HPLC等方法进行分离、纯化,运用1H-和13C-NMR,ESI-MS等谱学方法和技术对化合物结构进行鉴定.结果:从配剂金银花中间体中分离并鉴定了20个化合物,分别为黄酮类化合物:槐属苷(1)、木犀草素-7-O-葡萄糖苷(2)、芦丁(3)、槲皮素(4);绿原酸类化合物:3,5-O-双咖啡酰基奎宁酸甲酯(5)、4,5-O-双咖啡酰基奎宁酸甲酯(6)、3,4-O-双咖啡酰基奎宁酸甲酯(7)、4,5-O-双咖啡酰基奎宁酸(8)、3,4-O-双咖啡酰基奎宁酸(9)、绿原酸(10);环烯醚萜苷类化合物:表断马钱子苷半缩醛内酯(11)、獐牙菜苷(12)、断马钱子苷半缩醛内酯(13)、断氧化马钱子苷(14);皂苷类化合物:灰毡毛忍冬皂苷甲(15)、灰毡毛忍冬皂苷乙(16)、忍冬苦苷A(17)、忍冬苦苷B(18)、忍冬苦苷C(19)、续断皂苷B(20).结论:化合物1为首次从该属植物中发现,1～20均为首次从配剂金银花中间体中分离得到.     

梓葛冻干粉对人脐静脉内皮细胞缺氧/ 复氧损伤的保护作用

目的:研究中药单体组方梓葛冻干粉对人脐静脉内皮细胞(HUVECs)缺氧/复氧损伤的保护作用。方法:体外培养HUVECs,采用Krebs液建立缺氧/复氧损伤模型。用梓葛冻干粉干预后,采用MTT比色法测定细胞活力、黄嘌呤氧化酶法测定细胞内超氧化物歧化酶(SOD)活性、硫代巴比妥酸显色法测定丙二醛(MDA)含量、硝酸还原酶法测定一氧化氮(NO)含量、2,4-二硝基苯肼显色法测定细胞外乳酸脱氢酶(LDH)释放量;Western blot法分析细胞凋亡相关蛋白Bcl-2,Bax,Caspase-3的表达。结果:与模型组相比,梓葛冻干粉12.5 mg.L-1显著提高细胞活力(P<0.05);梓葛冻干粉49.0,24.5,12.5 mg.L-1均显著提高缺氧/复氧后细胞SOD活性(P<0.05);梓葛冻干粉24.5,12.5 mg.L-1能显著减少LDH的释放量及降低MDA和NO的含量(P<0.05),并上调细胞Bcl-2蛋白表达(P<0.05,P<0.01);梓葛冻干粉49.0,24.5,12.5 mg.L-1显著降低Bax的表达并上调Bcl-2/Bax(P<0.05,P<0.01),且梓葛冻干粉49.0,24.5 mg.L-1显著降低Caspase-3的表达(P<0.01)。结论:梓葛冻干粉可显著拮抗缺氧/复氧对HUVECs的损伤,可能与其抑制细胞过氧化损伤,增强细胞抗氧化和抗凋亡能力有关。     

索拉非尼固体脂质纳米粒冻干粉制备及体外释药特性研究

 目的 制备索拉非尼固体脂质纳米粒,并考察其理化性质及体外释药特性。方法 采用乳化蒸发-低温固化法制备索拉非尼固体脂质纳米粒,透射电镜观察形态,激光粒度仪测定粒径和Zeta电位,葡聚糖凝胶法和HPLC测定其包封率,透析法考察其体外释药特性,冷冻干燥法制备索拉非尼固体脂质纳米粒冻干粉,差示扫描量热分析其物相状态。结果 制得索拉非尼固体脂质纳米粒为类球形实体,粒径分布比较均匀,平均粒径为(108.2±7.0) nm,多分散指数为（0.250±0.022）,Zeta电位为(-16.4±0.7) mV;测得3批样品的平均包封率为(73.49±1.87)%;体外释放符合Weibull模型;等体积15%甘露醇作冻干保护剂效果较好;DSC分析证明纳米粒已形成。结论 乳化蒸发-低温固化法适用于索拉非尼固体脂质纳米粒的制备,所制纳米粒各项物理指标稳定,具有明显缓释作用。     

注射用丹参(冻干)抗人血小板聚集标准研究

目的以确定注射用丹参(冻干)对血小板聚集抑制率的限度标准为目的 ,确定血小板聚集率指标符合生产和临床实际。方法采集人血进行初步处理,将测定样品制成适宜浓度的溶液,将适宜用量的样品溶液和人血混合后测定血小板聚集率,计算其血小板聚集抑制率。进行重复性试验和重现性试验,确定血小板聚集抑制率限度标准。结果本实验的注射用丹参(冻干)对血小板聚集抑制率限度标准的下限为25.1±9.2。结论该试验提供的方法可行,可以确定小板聚集抑制率的限度标准。     

Optimization and evaluation of lyophilized fenofibrate nanoparticles with enhanced oral bioavailability and efficacy

Abstract

The objective of this study was to enhance physiochemical properties as well as oral bioavailability of the poorly water soluble drug fenofibrate (FB), through preparation of amorphous solid dispersions (ASDs). ASDs were prepared via freeze drying using polyvinylpyrrolidone (PVP) K30 and poloxamer 188 as hydrophilic carriers. Formulations were optimized by 3² full factorial design (FFD) with PVP-K30 level (X₁) and poloxamer 188 level (X₂) as independent variables and particle size (Y₁), zeta potential (Y₂), drug content (Y₃) and dissolution rate (T90, [Y₄]) as dependent variables. Optimized FB nanoparticles were physicochemically evaluated and formulated into lyophilized sublingual tablets. Pharmacokinetic, pharmacodynamics and histological finding of optimized formulation were performed on rabbits. Y₁ and Y₄ were significantly affected by independent variables while Y₂ and Y₃ were not affected. Physicochemical characterization showed the drug was in amorphous state, nanometer range and pharmacophore of FB was preserved. Administration of optimized FB tablets to rabbits with fatty liver led to significant reduction (p?<?0.001) in serum lipids. Moreover, histological analysis of liver specimens confirmed the improved efficacy in animals with fatty liver. In this study, we confirmed that ASDs of FB had beneficial effects on managing fatty liver and serum lipids level in hyperlipidemic rabbits.     

The vial kit formulation for preparation of no‐carrier‐added 131I‐MIBG

We have developed a new set of lyophilized kits, composed of 3 different kits, for the instant preparation of no‐carrier‐added ¹³¹I‐MIBG in the clinic. We here discussed the formulation of the kits, optimization of radiolabelling, quality control of radiolabeled ¹³¹I‐MIBG, and studies of animal biodistribution. The no‐carrier‐added (nca) ¹³¹I‐MIBG injection could be prepared within 30 minutes in the clinic with the help of the lyophilized kits. The radiochemical purity and specific activity (SA) could achieve above 98% and 6700 MBq/mg, respectively.     

Development of a novel quantitative real‐time PCR assay with lyophilized powder reagent to detect African swine fever virus in blood samples of domestic pigs in China

African swine fever (ASF) is a devastating disease, which is causing huge economic losses in China. Therefore, it is urgent to provide a rapid, highly specific and sensitive diagnostic method for the detection of African swine fever virus (ASFV), the ASF infectious agent. In this study, a novel quantitative real‐time polymerase chain reaction (qPCR) assay with lyophilized powder reagents (LPR), targeting the major structural protein p72 gene, was established for the detection of ASFV. This assay had many advantages, such as saving time and money, good sensitivity and repeatability. The sensitivity of this assay was 100 copies/μl of ASFV plasmid templates, and the assay showed 10‐fold greater sensitivity than a qPCR assay recommended by OIE. Furthermore, specificity analysis showed that qPCR with LPR for ASFV had no cross‐reactivity with other important swine pathogens. In clinical diagnoses of 218 blood samples of domestic pigs in China, the positive rate of the diagnosis of ASFV by qPCR with the LPR and commercial kit reached 80.73% (176/218) and 76.61% (167/218) respectively. The coincidence rate between the two assays is 92.20% (201/218), and kappa value is 0.768 (p < .0001) by SPSS analysis. The overall agreement between the two assays was 95.87% (209/218). Further Pearson correlation and linear regression analysis showed a significant correlation between the two assays with an R² value of 0.9438. The entire procedure, from specimen processing to result reporting, can be completed within 2 hr. Our results demonstrated that the qPCR‐LPR assay is a good laboratory diagnostic tool for sensitive and efficient detection of ASFV.     

Photolytic Labeling and Its Applications in Protein Drug Discovery and Development

In this mini-review, the major types of photolytic labeling reagents are presented together with their reaction mechanisms. The applications of photolytic labeling in protein drug discovery and development are then discussed; these have expanded from studies of protein-protein interactions in vivo to protein-matrix interactions in lyophilized solids. The mini-review concludes with recommendations for further development of the approach, which include the need for new and more chemically diverse photo-reactive reagents and better understanding of the mechanisms of photolytic labeling reactions in various media.