The role of solvents in the signal separation for quantitative H NMR spectroscopy

Compared to conventional means of quantitative drug analysis, NMR spectroscopy only provides a limited set of adjustable parameters to enhance the quality of the analysis such as pH value, temperature, auxiliary reagents, magnetic field strength or properties of the solvent. In this work we investigate the influence of the kind of solvent on the signal separation of decisive resonances in the NMR spectra of codergocrine mesilate and flupentixol dihydrochloride. Polarity and aromaticity of the solvent play a crucial role in the optimization of signal separation. However, the set of applicable solvents is usually limited due to certain boundary conditions like solubility of the agent. Therefore the effects of solubilizers as well as mixtures solvents on the chemical shift also have to be taken into account. The quantitative results obtained by means of ¹H NMR spectroscopy were found to be in good agreement with the results carried out using official HPLC methods of International Pharmacopoeias.     

Subtyping of human cellular prion proteins and their differential solubility

A human form of a prion disorder is the Creutzfeldt-Jakob disease. A hallmark of the disease is the accumulation of misfolded prion proteins (PrP^Sc), which exist as heterogeneous subtypes. PrP^Sc is formed by protein conversion from the host-encoded cellular prion (PrP^C), which is expressed and modified to various isoforms. Little is known about variation in PrP^C; however, it is assumed that PrP^C types play important roles in the formation of PrP^Sc. In this study, we separated distinct human PrP^C subtypes on the basis of differential protein solubilities in detergent solutions. Single and sequential application of the detergents Triton X-100, octyl-glucopyranoside and CHAPS facilitated high solubility of glycosylated PrP^C isoforms, whereas high proportions of nonglycosylated PrP^C remained non-soluble. Most proteins became highly soluble with laurylsarcosine and sodium dodecyl sulphate. Our findings demonstrate that the solubility characteristics of heterogeneous PrP^C overlap in human brains and convey distinct solubility subtypes. Differentiation by solubility experiments can therefore provide valuable information on prion protein composition, facilitate the separation of subtypes, and offer new prospects for conversion specificity of distinct isoforms.     

自制复方溶石剂的体外溶石作用及毒性的初步研究

目的 评价自制复方溶石剂的体外溶石效果和毒性作用。方法 用甲基叔丁醚(MT—BE)作用对照,在体外对胆固醇、混合性、胆色素性结石进行溶石实验以及在20只兔胆囊内灌注溶石剂后观察血生化和各脏器的病理改变。结果 自制复方溶石剂对胆固醇、混合性、胆色素性结石的溶石比例分别达到97．20％、88．43％、82．69％;毒性比MTBE小。结论 自制复方溶石剂是一种相对低毒、安全、对大多数胆道结石有良好效果的直接溶石剂。     

铝碳酸镁不同给药方法对反流性食管炎的近期疗效观察

目的：铝碳酸镁（达喜）不同给药方法治疗反流性食管炎，通过进行胃镜观察疗效对比，探索反流性食管炎的治疗新方法。方法：将胃镜下诊断为Ⅱ级以上的RE患者106例，随机分成两组，治疗组采用铝碳酸镁溶于水，小口慢咽，对照组用铝碳酸镁片剂给药，按同等剂量治疗10 d复查胃镜。结果：治疗组总有效率显著高于对照组，经χ^2检验，两组总有效率有非常显著性差异（P〈0.01）。结论：采用铝碳酸镁水溶剂小口慢咽的给药方法，让药物与病灶局部充分接触是治疗反流性食管炎，尤其是Ⅱ级以上糜烂性食管炎非常有效的方法。     

Neurotoxicity of solvents in brain of glue abusers

We reviewed the neuropathological changes in 12 forensic autopsies during a period of 6 months in cases with glue abuse suspicion, and observed specific macroscopic and microscopic changes in the brain with emphasis on the white matter substance.

The information of this study was taken from the investigation documents, laboratory results, and neuropathological observations.

The results were compared with the literature of neurotoxicology on solvents, especially with the examples caused by toluene and coincidences among them were described.

The results showed changes related with solvents leukoencephalopathy: multifocal alterations, diminishment, loss and fragmentation of myeline density, conservation of neural filaments and neuropile vacuolization without inflammatory changes. A characterization of the cases was made and an average age of 28.8 was presented. In Colombia, the principal solvent legally used is toluene, but it is possible that other hydrocarbons are involved.     

香叶木素固体脂质纳米粒的制备及质量评价

目的 制备香叶木素固体脂质纳米粒并对其进行质量评价。方法 采用溶剂注入法制备香叶木素固体脂质纳米粒,用 Box-Benhnken效应面法优化处方,并通过包封率、微观形态、粒径分布和Zeta电位对香叶木素固体脂质纳米粒的质量进行评价。 结果 香叶木素固体脂质纳米粒最优处方组成：表面活性剂浓度3.39%,棕榈酸浓度0.116%,脂药质比为21:100,制备的香叶木素 固体脂质纳米粒外观澄清透明,带淡蓝色乳光;平均粒径为(91.73±3.18)nm(n=3),PDI为0.228,电位为(-11.46±0.74)mV(n=3);包 封率为95.13%,载药量为9.04%;透射电镜照片显示纳米粒大小均一,呈球形或类球形。 结论 该处方可用于香叶木素固体脂 质纳米粒的制备,工艺简单,稳定可行。     

工作场所空气中甲苯溶剂解吸气相色谱法测定的不确定度评定

目的建立工作场所空气中甲苯的溶剂解吸气相色谱法测定的不确定度评定方法,通过控制这些因素提高检测结果的置信度和准确性。方法依据中华人民共和国国家计量技术规范JJF1059-1999《测量不确定度评定与表示》和中国金属学会推荐的技术和方法CCM010100-2006《化学仪器分析测量结果不确定度评定导则》。结果甲苯不确定度主要来源:①测量重复性的不确定度;②标准溶液配制过程的不确定度;③标准曲线的变动性的不确定度;④采样过程的不确定度;⑤解吸效率的不确定度;⑥样品解吸的不确定度。取包含因子k=2,扩展不确定度为U=1.7540×2≈3.51mg/m3。结论该不确定度评定方法对甲苯的溶剂解吸气相色谱法检测过程的质量控制意义十分重大,是提高检测结果的置信度和准确性的保证。     

Urinary disposition of ethylbenzene and m-xylene in man following separate and combined exposure

Summary Four volunteer subjects were exposed to 150ppm (655 mg/m³) of ethylbenzene and 150ppm (655mg/m³) of m-xylene both separately and in combination. The biotransformation of the solvents was studied on the basis of the metabolites found in the urine. The metabolic conversion of both m-xylene and ethylbenzene proceeded mainly through oxidation of side chains. Ring oxidation seemed to be of minor importance; in the case of ethylbenzene it accounted for 4.0% (combined share of 4-ethylphenol, p- and m-hydroxyacetophenones) and in case of m-xylene for 2.5% (2,4 dimethylphenol), respectively. Mandelic and phenylglyoxylic acids amounted to 90% of the ethylbenzene metabolites, whereas m-xylene were excreted to 97% in the form of m-methylhippuric acid. Almost equimolar amounts in the form of metabolites of both solvents were found in the urine during 24h from the onset of exposure. Most of the ethylbenzene metabolites were excreted at substantially slower rates than those of m-xylene. The combined exposure resulted in a mutual inhibition of the metabolism of ethylbenzene and m-xylene, which was demonstrated by delayed excretion and decreased amounts of metabolites excreted. No sign of alteration in the urinary metabolite patterns of either ethylbenzene or m-xylene could be detected.     

祁州漏芦不同溶剂提取物对急性肝损伤模型小鼠的保护作用

目的:研究祁州漏芦(以下简称"漏芦")不同溶剂提取物对急性肝损伤模型小鼠的保护作用。方法:60只KM种小鼠随机分为正常对照(等容生理盐水)组、模型(等容生理盐水)组、联苯双酯(100 mg/kg)组、漏芦乙醇粗提物(200 mg/kg)组、漏芦正丁醇提取物(200 mg/kg)组和漏芦水提取物(200 mg/kg)组。灌胃给药,每天1次,连续7 d。末次给药1 h后,一次性腹腔注射300 mg/kg对乙酰氨基酚(APAP)以复制小鼠急性肝损伤模型。比色法检测小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、白蛋白(ALB),肝匀浆丙二醛(MDA)、还原型谷胱甘肽(GSH)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)、谷胱甘肽-S-转移酶(GST),肝线粒体Na+-K+-ATP酶(Na+-K+-ATPase)、Ca2+-Mg2+-ATP酶(Ca2+-Mg2+-ATPase)水平。结果:与正常对照组比较,模型组小鼠血清ALT、AST和ALP活性增强,ALB含量降低;肝组织MDA含量增加,CAT、GPx、SOD、GST活性减弱,GSH含量减少;肝线粒体Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性减弱,差异具有统计学意义(P<0.05)。与模型组比较,漏芦乙醇粗提物组小鼠血清ALT、AST活性减弱,ALB含量增加,肝匀浆MDA含量减少,GSH含量增加,CAT、GPx、SOD、GST活性增强,肝线粒体Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性增强,差异具有统计学意义(P<0.05);漏芦正丁醇提取物组小鼠血清ALT、AST、ALP活性减弱,ALB含量增加,肝匀浆MDA含量减少,GSH含量增加,CAT、GPx、SOD、GST活性增强,肝线粒体Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性增强,差异具有统计学意义(P<0.05);漏芦水提取物组小鼠血清ALT、AST活性减弱,ALB含量增加,肝匀浆MDA含量减少,GSH含量增加,GPx、GST活性增强,肝线粒体Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性增强,差异具有统计学意义(P<0.05)。结论:漏芦不同溶剂提取物对APAP致小鼠急性肝损伤具有保护作用,其机制可能与其抗氧化作用有关。     

Dissolution Improvement of Atorvastatin Calcium using Modified Locust Bean Gum by the Solid Dispersion Technique

The present research was aimed at the enhancement of the dissolution rate of atorvastatin calcium by the solid dispersion technique using modified locust bean gum. Solid dispersions (SD) using modified locust bean gum were prepared by the modified solvent evaporation method. Other mixtures were also prepared by physical mixing, co-grinding, and the kneading method. The locust bean gum was subjected to heat for modification. The prepared solid dispersions and other mixtures were evaluated for equilibrium solubility studies, content uniformity, FTIR, DSC, XRD, in vitro drug release, and in vivo pharmacodynamic studies. The equilibrium solubility was enhanced in the solid dispersions (in a drug:polymer ratio of 1:6) and other mixtures such as the co-grinding mixture (CGM) and kneading mixture (KM). Maximum dissolution rate was observed in the solid dispersion batch SD3 (i.e. 50% within 15 min) with maximum drug release after 2 h (80%) out of all solid dispersions. The co-grinding mixture also exhibited a significant enhancement in the dissolution rate among the other mixtures. FTIR studies revealed the absence of drug-polymer interaction in the solid dispersions. Minor shifts in the endothermic peaks of the DSC thermograms of SD3 and CGM indicated slight changes in drug crystallinity. XRD studies further confirmed the results of DSC and FTIR. Topological changes were observed in SEM images of SD3 and CGM. In vivo pharmacodynamic studies indicated an improved efficacy of the optimized batch SD3 as compared to the pure drug at a dose of 3 mg/kg/day. Modified locust bean gum can be a promising carrier for solubility enhancement of poorly water-soluble drugs. The lower viscosity and wetting ability of MLBG, reduction in particle size, and decreased crystallinity of the drug are responsible for the dissolution enhancement of atorvastatin. The co-grinding mixture can be a good alternative to solid dispersions prepared by modified solvent evaporation due to its ease of preparation and significant improvement in dissolution characteristics.