锡－中卟啉毒性及应用的实验研究

锡－中卟啉毒性及应用的实验研究李佩红，俞善昌，李云珠，陈舜年锡－中卟啉（Ｓｎ－ｍｅｓｏｐｏｒｐｈｙｒｉｎＳｎＭＰ）和锡－原卟琳（Ｓｎ－ｐｒｏｔｏｐｏｒｐｈｙｒｉｎ）是一类与天然血红素相似的人工合成化合物。能竞争性抑制微粒体血红素加氧酶，阻断血红素代谢...     

碱性注射液应避免用混合纤维素酯微孔滤膜过滤

国内用于注射液过滤的微孔滤膜是由硝酸、醋酸纤维素混合酯所制成。在通常情况下,酯的水解速度较慢。但在碱性介质中,碱能中和水解反应中生成的酸,使反应平衡破坏,而加速了水解反应的进行。所以混合纤维素酯微孔滤膜过滤碱性注射液很容易水解破裂,使注射液产生纤维。     

鹿骨保健食品原料的工艺研究

以鹿骨初酶解产物为研究对象,以水解度为特征性指标,采用甲醛滴定法检测酶解进程,分析对比不同酶解条件对样品水解度的影响,确定了碱性蛋白酶和胰蛋白酶分步水解为最佳酶解条件。结果：采用碱性蛋白酶和胰蛋白酶分步水解的最佳,条件为酶底比1∶200和1∶240,料液比为1∶40,起始pH值为9.0,碱性蛋白酶45℃酶解1.5h后,加入胰蛋白酶37℃下酶解2h,水解度为21.37%。     

超声促进4，4—二取代—3—苯基—2—恶唑啉—5—酮的水解

目的：碱性水 4,4－二取代－2－苯基－2－恶唑啉－5－酮1,方法：用超声波促进1水解。结果：1在超声波作用下很快水解,生成N－苯2-2, 取代－2－氨基乙酸,没有超声辐照,室温水解需搅拌24h,而有超声辐照,反应仅需15min,结论：超声波能有效促进1的碱性水解。     

1,3—溴氯丙烷的水解动力学研究

<正> 本研究题目是结合我院药厂合成双安妥明药物需要1,3-丙二醇为原料而进行的,利用药厂生产的1,3-溴氯丙烷在碱性水溶液中水解法制备1,3-丙二醇,除考查了1,3-溴氯丙烷的水解工艺条件与中型生产试剂外,并进行了水解动力学的研究,测定了反应级数,得出在本实验条件下为假一级反应,而不同于一般伯仲卤代烃水解为二级反应的结论与文献报导不     

二丙酸倍他米松水解产物研究

目的:对二丙酸倍他米松主要水解产物的结构进行鉴定,为其稳定性及制剂处方研究提供参考。方法:对二丙酸倍他米松原料药进行强制降解试验,采用高效液相色谱法对水解产物进行分析、质谱法对水解产物进行结构鉴定,并利用合成所得杂质对照品对降解产物的结构进行确证。结果:二丙酸倍他米松在碱性和酸性条件下均可进行水解反应,且降解杂质不相同。其可水解产生倍他米松17-丙酸酯与倍他米松21-丙酸酯,2种单丙酸酯均可进一步水解成倍他米松。但二丙酸倍他米松在碱性条件下极易水解,降解产物可进一步降解;在酸性条件下水解则需要相对较强的反应条件,降解产物不易进一步水解。结论:二丙酸倍他米松在碱性和酸性条件下的水解杂质不相同,其3个主要的水解产物分别为倍他米松17-丙酸酯、倍他米松21-丙酸酯及倍他米松。     

四种不同类型酶降解壳聚糖的效果比较

目的：对4种不同类型酶水解壳聚糖的效果进行比较。方法：通过碱性铁氰化钾测定还原端基法测定了酶活性和溶液中还原糖浓度，研究并评价了纤维素酶、脂肪酶、溶菌酶和胃蛋白酶对壳聚糖溶液的降解条件和效果。结果：分别在4种酶的最适宜条件下反应，胃蛋白酶对壳聚糖水解速度最快，纤维素酶的水解速度仅次于胃蛋白酶，溶菌酶的水解速度最慢。结论：胃蛋白酶对壳聚糖的降解速度优于纤维素酶、脂肪酶和溶菌酶。     

绿原酸水解产物的高效液相色谱—电喷雾串联质谱分析

目的:分析双黄连方药制备过程中影响绿原酸水解的因素及可能的水解产物。方法:采用高效液相色谱-电喷雾串联质谱法分析绿原酸在不同pH值条件及不同水解时间的水解产物。结果:绿原酸在pH6.85的水溶液中较稳定,在酸性条件下比碱性条件下稳定。结论:绿原酸的水解模式主要有分子间酯键断裂、咖啡酰基迁移、水合反应等。     

血清碱性磷酸酶微量测定法及正常值

血清碱性磷酸酶活力测定,常用布氏及改良金氏法等,用血量较多,操作亦较麻烦。我们用磷酸麝香草酚酜铵盐之二乙醇胺缓冲液作基质进行微量碱性磷酸酶测定,对1,420名健康儿童及210名健康成人进行了正常值测定。操作简便及准确性均称满意。一、原理血清中碱性磷酸酶在pH10.1二乙醇胺缓冲液中,能将磷酸麝香草酚酜铵盐水解成磷酸铵和麝     

麦迪霉素对枯草杆菌碱性磷酸酶的作用

麦迪霉素(Mydecamycin)明显地抑制枯草杆菌BF7658的生长。在无机磷酸的含量受到限制的培养基中生长的枯草杆菌BF7658的细胞,能迅速地诱导生成碱性磷酸酶。在碱性磷酸酶诱导合成的过程中,加进0.5微克/毫升的麦迪加霉素,该酶的合成几乎完全被阻遏。在碱性磷酸酶催化腺苷酸(AMP)水解的反应液中,即使加进100微克/毫升的麦迪霉素,该酶的催化活性也不受抑制。     

Targeted Delivery of a Heme Oxygenase Inhibitor with a Lyophilized Liposomal Tin Mesoporphyrin Formulation

Tin mesoporphyrin (SnMP) is a competitive inhibitor of heme oxygenase being examined clinically for the treatment of hyperbilirubinemia. Since liposomes have been shown to target SnMP to the spleen and increase its efficacy (S. A. Landaw, G. S. Drummond, and A. Kappas, Pediatrics 84, 1091–1096, 1989), we began investigating the feasibility of the preparation and scaleup of a liposomal SnMP formulation for clinical use. SnMP liposomes were prepared by high-pressure homogenization of a suspension of SnMP and egg phosphatidylcholine (1:20, w/w) in lactose-phosphate buffer, resulting in SnMP liposomes that were less than 200 nm in diameter and had encapsulation efficiencies of up to 90% at pH 5. The SnMP liposomes could be sterile filtered and lyophilized in a 1-day cycle with retention of the encapsulation efficiency and particle size. Following injection into rats, the distribution of liposomal SnMP to spleen at 2 and 6 hr after dosing was 5–20 times higher than for aqueous SnMP. Lyophilized SnMP liposomes were also more effective than aqueous SnMP in decreasing bilirubin production in bile-cannulated rats. The results suggest the potential for producing a safe, sterile, and effective lyophilized formulation of SnMP liposomes for targeting of heme oxygenase inhibitors to the spleen.     

锡类散贴片制备工艺及稳定性、黏附性和释放性能的研究

目的:制备锡类散贴片并研究其配方比例、稳定性、黏附性及释放度。方法:通过测定锡类散贴片的稳定性、黏附性和释放性能.确定其配比和工艺。结果:最佳配比为羧甲基纤维素钠(CMC-Na):低取代羟丙基纤维素(L-HPC):锡类散=1:1.1:0.94,此时贴片具有较好的药物黏附性能且性质稳定,并具有缓释作用。结论:按该配比制备的贴片既有良好的黏附作用又可定位释放,延长了药物与病灶部位的作用时间,提高了疗效。     

替硝唑与甲硝唑治疗滴虫性阴道炎疗效比较

目的：比较替硝唑和甲硝唑治疗滴虫性阴道炎的疗效。方法：６０例滴虫性阴道炎病人，随机单盲分为２组。替硝唑组３０例，年龄３３±ｓ５ａ（２２～５１ａ），用替硝唑治疗，首日顿服２．０ｇ，ｄ２，ｄ３各顿服１．０ｇ，疗程３ｄ。甲硝唑组３０例，年龄３６±７ａ（２０～５２ａ），用甲硝唑０．２ｇ，ｐｏ，ｔｉｄ，疗程７ｄ。结果：替硝唑组和甲硝唑组总有效率分别为８７％和８０％，２组疗效比较无显著差异（Ｐ＞０．０５），但不良反应发生率分别为２３％和７０％，有显著性差异（Ｐ＜０．０１）。结论：替硝唑治疗滴虫性阴道炎疗程短，不良反应小。     

Vascular endothelial growth factor increases heme oxygenase-1 protein expression in the chick embryo chorioallantoic membrane

(1) Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. It has been recently suggested that the inducible heme oxygenase (HO-1) isoform may play a role in angiogenesis. (2) The aims of this study were to determine, in chicken embryo chorioallantoic membranes (CAM), whether VEGF increases HO-1 protein expression, and, if so, by which molecular mechanism, and whether HO-1 activity is required for VEGF-induced angiogenesis. (3) Treatment of CAMs with VEGF for 48 h caused a significant increase in HO-1 protein expression, simultaneously with angiogenesis. (4) VEGF-stimulated angiogenesis in CAMs was markedly attenuated by the HO inhibitor zinc mesoporphyrin (ZnMP). This inhibitory effect of ZnMP was not observed with copper mesoporphyrin (CuMP), a metalloporphyrin that has a similar structure to ZnMP but does not inhibit HO enzymatic activity. (5) Overexpression of HO-1 protein elicited by VEGF in CAMs was significantly attenuated by the intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM). The effects of BAPTA-AM were, in turn, compensated by the calcium ionophore A-23187. (6) In addition, the protein kinase C inhibitor staurosporine significantly attenuated, in a dose-dependent manner, the VEGF-stimulated HO-1 induction observed in CAMs. (7) These results demonstrate, for the first time, that VEGF upregulates HO-1 protein expression in vivo in CAMs by a mechanism dependent on an increase in cytosolic calcium levels and activation of protein kinase C. Our findings also suggest that HO-1 activity is necessary for VEGF-induced angiogenesis in CAMs.     

Dose-dependent brain tin concentration in rats given stannous chloride in drinking water

Male Wistar rats were given either 100 mg SnCl2 X 2H2O per litre (0.44 mM), 250 mg/l (1.11 mM) or 500 mg/l (2.22 mM) in their drinking water for 1-18 weeks. Tin detected by a novel atomic absorption spectrophotometric method accumulated in the cerebrum at the highest dose level (2.22 mM) throughout the experiment. In brain, tin concentrations above the 1.11-mM dose were only found after 15 and 18 weeks. Tin did not increase in the brain at the 0.44-mM dose level. Blood tin increased promptly after one week at the highest dose (2.22 mM) without further accumulation. Blood tin at the 0.44 mM dose level did not differ from controls. Tin exposure caused a dose-dependent increase in the cerebral and muscle acetylcholinesterase activity at the two higher doses.     

GC测定二-(2,6-二氟苯甲酰异羟肟酸)二正丁基合锡中有机溶剂残留量

目的建立原料药二-（2,6-二氟苯甲酰异羟肟酸）二正丁基合锡中的有机溶剂残留量的测定方法。方法采用毛细管气相色谱法,FID检测器,DB-1毛细管柱,柱温50℃,进样口温度200℃,检测器温度220℃,流速为2.0 mL.min-1,分流比为50∶1,以1,2-二氯乙烷为内标测定溶剂残留量。结果甲醇、正己烷、甲苯在考察的浓度范围内线性关系良好,线性范围分别为9~375μg.mL-1（r=0.999 8）,0.87~36.25μg.mL-1（r=0.999 7）,2.67~111.25μg.mL-1（r=0.999 8）,平均回收率分别为99.1%（RSD=2.5%）、98.3%（RSD=2.7%）、99.7%（RSD=1.3%）。结论本方法快速、简单、结果准确,可用于二-（2,6-二氟苯甲酰异羟肟酸）二正丁基合锡中的有机溶剂残留量的测定。     

中西医结合治疗恶性胸腔积液16例观察

目的 观察中西医结合恶性胸腔积液的疗效。方法 口服中药葶苈大枣泻肺汤加减,胸穿抽液后注射沙培林针剂,配合对症支持治疗,结果 16例病人5例完全缓解,9例部分缓解。2例无效,总有效率87.5%。结论 中西医结合治疗恶性胸水,在缓解及消除症状,体征方面有较好疗效。     

Utilization of ion exchanger and spectrophotometry for assaying amoxycillin and flucloxacillin in dosage form

A simple, rapid, accurate sensitive spectrophotometry procedure for the determination of amoxycillin (Amox) and flucloxacillin (Fluclox) in bulk samples and in dosage forms are developed. The procedure involves the use of sudan III as chromogenic reagent to produce a violet colored ion-pair with an absorption maximum at 566nm. The ion-pair complexes obey Beer's law and are suitable for the quantitative determination of 0.2-22 and 0.4-25microg/ml of Amox, and Fluclox, respectively. The optimization of different experimental conditions is described in which Amox react after 3min at 25+/-1 degrees C, whereas Fluclox take 10min at 60+/-1 degrees C. Tin(IV) antimonite ion exchanger was utilized to separate a mixture of Amox and Fluclox trihydrate. A column chromatographic technique was applied to separation the antibiotics mixture. Column of 0.3mm diameter and bed height of 3cm of the exchanger was used and the frontal elution technique was utilized. The separation factor for Fluclox and Amox was found to be 2.76. Tin(IV) antimonite ion exchanger exhibit promising feature that can be utilized as stationary phase in either HPLC or HPTLC techniques. The procedure described was applied successfully to determine Amox and Fluclox. The obtained results were compared the official methods. The proposed procedure was successfully applied to determine Amox and Fluclox in their pharmaceutical formulations.     

Effect of tin on porphyrin biosynthesis

Certain disturbances in porphyrin biosynthesis were examined in rabbits administered with either tin or lead. Stannous chloride treatment increased the concentrations of coproporphyrin in blood and urine, as did lead acetate treatment. No effect of tin on 5-aminolevulinic acid concentration was observed in blood and urine, whereas lead treatment increased it markedly in both. Tin profoundly inhibited the activity of 5-aminolevulinate dehydratase in blood, but did not alter it in liver although tin content in liver was considerably higher than that in blood. In contrast to a prolonged inhibition of erythrocyte 5-aminolevulinate dehydratase by lead, tin inhibition of erythrocyte 5-aminolevulinate dehydratase activity was rapidly reversed after the cessation of the metal treatment.     

Spinal cord heme oxygenase participates in glutamate-induced pain-related behaviors

Heme oxygenase catalyzes the formation of CO, Fe(2+) and biliverdin from the substrate heme. In these studies, we attempted to define the roles heme oxygenase play in pain-related behaviors induced by intrathecal injection of the spinal neurotransmitter glutamate. The intrathecal injection of glutamate or the more selective agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in C57Bl/6 mice lead to caudally directed pain behaviors which were sensitive to the heme oxygenase inhibitors tin protoporphyrin (Sn-protoporphyrin) and chromium mesoporphyrin (Cr-mesoporphyrin). Intrathecal injections of glutamate in heme oxygenase type 2 (HO-2) null-mutant animals resulted in reduced pain-related behaviors when compared with wild type animals. Glutamate, NMDA and AMPA stimulated cGMP accumulation in mouse spinal cord slices, which was blocked by heme oxygenase inhibitors. Glutamate did not stimulate cGMP production in HO-2 null-mutant animals. Our data are consistent with the hypothesis that pain-related behaviors induced by spinal glutamate rely on the activation of HO-2 and subsequent production of cGMP.