双氯芬酸钠贴剂相对生物利用度与局部组织药物浓度测定

目的 研究兔经皮给予双氯芬酸钠贴剂的相对生物利用度和局部组织药物浓度,为临床用药提供参考.方法 单剂量给予贴剂和凝胶剂,采用反相高效液相色谱法测定血浆和局部组织中的双氯芬酸钠浓度.结果 兔表皮给予双氯芬酸钠贴剂的药动学参数如下.AUC：22.63 μg•h•mL^-1,t1/2Ka：0.82 h,t1/2Ke：8.51 h,tmax：2.53 h,Cmax：1.64 μg•mL^-1,CL/F（s）：1.52 L•h^-1, Ka：1.15 h^-1,Ke：0.12 h^-1;凝胶剂在兔体内的药动学参数为AUC：13.07 μg•h•mL^-1, t1/2Ka：0.27 h,t1/2Ke：1.92 h,tmax：0.88 h,C_max：1.45 μg•mL^-1,CL/F（s）：1.71 L•h^-1;Ka：2.62 h^-1,Ke：0.37 h^-1,求算得双氯芬酸钠贴剂的相对生物利用度为173.14%.对2种制剂的药动学参数进行双侧t检验,均差异有显著性（均P＜0.05）.再对给予贴片和凝胶剂的兔皮肤、关节腔、血液3组之间进行LSD检验,各组差异有显著性,给予贴剂的皮肤中药物浓度是血浆的36.5倍,给予凝胶剂的皮肤中药物浓度是血浆的18.68倍.结论 双氯芬酸钠贴片的Cmax高于双氯芬酸钠凝胶外擦给药,贴片的AUC大于凝胶给药的AUC,但具有达峰时间长和在体内时间长的特点,具有长效作用,贴片的生物利用度优于凝胶.     

高效凝胶色谱法测定注射用盐酸头孢甲肟中的高分子杂质

目的 建立高效凝胶色谱法测定注射用盐酸头孢甲肟中的高分子杂质. 方法采用高效凝胶色谱法,色谱柱为高效凝胶Tsk gel G2000 SWxl(300 mm×7.8 mm,5 μm),流动相为pH7.0的0.005 mol•L^-1磷酸盐缓冲液[0.005 mol•L^-1磷酸氢二钠溶液 0.005 mol•L^-1磷酸二氢钠溶液(61:39)]-乙腈(95:5);流速:0.8 mL•min^-1;检测波长为234 nm,进样量为20 μL. 结果 供试品溶液在0.067～2.700 mg•mL^-1浓度范围内,溶液的浓度与高分子杂质的峰面积总和呈良好的线性关系(r＝0.998 8);盐酸头孢甲肟在0.001～0.010 mg•mL^-1浓度范围内,与峰面积呈良好的线性关系(r＝0.999 9). 结论 该测定方法简便,重复性好,可靠性高,可用于注射用盐酸头孢甲肟中高分子杂质的质量控制.     

动态浊度法定量检查注射用乙酰谷酰胺的内毒素含量

目的 应用动态浊度法鲎实验定量测定注射用乙酰谷酰胺中细菌内毒素含量. 方法 用 0.5,0.25,0.125,0.063,0.031 EU•mL^-1内毒素标准品溶液作标准曲线. 结果 通过对样品进行干扰预实验, 筛选出注射用乙酰谷酰胺最佳的检测浓度1 mg•mL^-1 , 进行正式干扰实验. 样品中定量添加内毒素0.125 EU•mL^-1, 回收率为50%～200% . 结论 浊度法鲎实验可有效检查注射用乙酰谷酰胺中的内毒素含量.     

治痔胶囊与槐角丸体外抑菌活性比较

目的 比较治痔胶囊与槐角丸的体外抑菌活性. 方法 采用琼脂稀释法,观察治痔胶囊与槐角丸溶液对6种常见细菌生长的抑制作用. 结果 治痔胶囊对常见的6种细菌均有抑菌作用,对金黄色葡萄球菌、变形杆菌、乙型链球菌的最低抑制浓度(minimal inhibitory concentration,MIC)为0.062 5 g•mL^-1,对铜绿假单胞菌的MIC为0.125 g•mL^-1,对大肠埃希菌的MIC为0.25 g•mL^-1,对肠球菌的的最低抑菌浓度为0.5 g•mL^-1.槐角丸对金黄色葡萄球菌、变形杆菌的生长有抑制作用,对两者的MIC均为0.125 g•mL^-1,槐角丸对另外4种细菌生长均无抑制作用. 结论 治痔胶囊比槐角丸具有更广的抗菌谱和更强的抑菌能力.     

丹参酮化合物对HeLa细胞抑制作用与构效关系探讨

目的 研究丹参酮化合物对HeLa细胞增殖的抑制作用,阐明其结构与细胞毒活性的关联性. 方法 MTT比色法检测不同浓度的丹参酮化合物,分别在24,48,72 h对HeLa细胞增殖的抑制作用. 结果 不同浓度（0.5～16.0 μg•mL^-1）丹参酮ⅡA、丹参酮I、二氢丹参酮、隐丹参酮对HeLa细胞毒性均有明显剂量和时间依赖性,其作用24 h的IC50值分别为：24.1,20.1,8.4,17.8 μg•mL^-1;作用48 h的IC₅₀值分别为：8.0,11.1,2.2,8.2 μg•mL^-1;作用72 h的IC₅₀值分别为：4.6,3.5,1.5,8.1 μg•mL^-1. 结论 丹参酮化合物对HeLa细胞均具有增殖抑制作用,其中二氢丹参酮对宫颈癌细胞系HeLa的细胞毒性最强. A环为芳香环与D环呋喃环的结构差别使其对HeLa细胞增殖的抑制作用有明显的差异.     

甲巯咪唑致粒细胞减少和肝损害及皮疹1例

患者,女,30岁.因心悸,怕热多汗,消瘦2个月,于2010年9月3日来我院就诊.入院体检：体温37.2 ℃,心率93次•min^-1,呼吸20次•min^-1,血压110/70 mmHg(1 mmHg=0.133 kPa),实验室检查血白细胞 5.9×109•L^-1,中性粒细胞计数3.4×109•L^-1;血生化丙氨酸氨基转移酶(alanine aminotransferase,ALT)22 U•L^-1、天冬氨酸氨基转移酶(aspartate aminotransferase,AST) 28 U•L^-1等均正常;尿常规正常.甲状腺功能检测：总三碘甲状腺原氨酸3.19 nmol•L^-1,甲状腺素总量16.81 nmol•L^-1,促甲状腺激素0.01 U•L^-1,游离三碘甲状腺原氨酸11.24 pmol•L^-1,游离甲状腺素2.49 pmol•L^-1.甲状腺超声显示：甲状腺回声不均并血流丰富改变.诊断：甲状腺机能亢进(甲亢).给予甲巯咪唑片10 mg,bid,普萘洛尔片10 mg,tid,po.用药15 d后患者躯干、四肢及面部出现红色皮疹,高出皮面,伴有刺痒,以双髋部及膝盖等处为著,并有食欲下降、恶心等症状.体检：体温37.1 ℃,心率95次•min^-1.复查血常规及生化：白细胞3.2×109•L^-1,中性粒细胞1.8×109•L^-1,ALT 175 U•L^-1,AST 67 U•L^-1.考虑为甲巯咪唑引起的白细胞减少、肝功能异常及皮疹,遂停用甲巯咪唑,其他治疗不变,并给予还原型谷胱甘肽1.2 g + 0.9%氯化钠注射液250 mL,qd,静脉滴注;氯雷他定10 mg,qd,po;利可君40 mg,tid,po,盐酸小檗胺4片,tid,po.6 d后复查血白细胞 4.37×109•L^-1,中性粒细胞3.0×109•L^-1,皮疹逐渐消失.继续给予保肝治疗,1周后复查肝功能：ALT 24 U•L^-1,AST 18 U•L^-1.逐步恢复至正常值     

柱切换高效液相色谱法测定血浆左氧氟沙星浓度

目的 应用柱切换高效液相色谱(HPLC)技术直接测定血浆中左氧氟沙星的浓度.方法 采用手动柱切换装置,分析柱采用大连依利特公司的Hypersil ODS C18柱（200 mm×4.6 mm,5 μm）,预柱采用μBondapak C18（50 mm×4.6 mm,37～50 μm,干法自填）.分析流动相（AMP）为甲醇 磷酸二氢钾缓冲液（0.01 mol•L-1,pH值＝2.5） 四丁基溴化铵（0.05 mol•L-1） 三乙胺＝40：60：4：0.2（V/V）;预处理流动相（PMP）为磷酸二氢钾缓冲液（0.01 mol•L^-1,pH值＝2.5） 四丁基溴化铵（0.05 mol•L^-1）＝100：1（V/V）.分析流动相流速1 mL•min^-1,预处理流动相流速2 mL•min^-1.检测波长为294 nm.结果左氧氟沙星在100～8 000 ng•mL^-1内有良好的线性关系.相关系数r＝0.999 8,方法平均相对回收率98.8%,日内及日间差小于10%,最低检测限0.05 μg•mL^-1（S/N≥3）.结论 样品无须预处理,直接进样分析测定,简便易行.     

美西律致超敏反应综合征1例

患者, 女, 47岁. 因全身红斑丘疹、微痒1周入院. 患者1周前无明显诱因颜面、前臂出现米粒大红斑丘疹, 微痒, 渐增多, 波及躯干下肢, 当地以“病毒疹”给予氯雷他定、维生素C、利巴韦林、复方甘草酸苷及中药等治疗, 红斑丘疹增多, 泛发全身, 融合成片, 躯干为重, 颜面出现红肿, 伴发热畏寒, 体温37.7～38.0 ℃, 病情进行性加重. 患者1个月前因心慌于外院做动态心电图, 诊断为室性期前收缩, 予美西律片,, 每次100 mg, tid, 服用1个月后出现皮疹. 否认药物、食物致变态反应史. 体检：体温38.2 ℃, 脉搏90次•min^-1, 呼吸20次•min^-1, 血压90/68 mmHg（1 mmHg＝0.133 kPa）, 精神差, 耳后、颈侧可触及数个绿豆大淋巴结, 无压痛, 咽充血, 心、肺、腹无异常. 皮肤科检查：全身皮肤泛发米粒大红斑丘疹, 融合成片, 压之退色, 躯干为重, 颜面红肿. 实验室检查：血常规示白细胞20.9×109•L ^-1, 血小板357×109•L -1, 中性粒细胞绝对值12.8×109•L^-1, N 0.609, 淋巴细胞绝对值3.7×109•L ^-1, L 0.176, 单核细胞绝对值1.58×109•L ^-1, 分类7.56%, 嗜酸性粒细胞绝对值2.52×109•L ^-1, 分类12%; C 反应蛋白（CRP）19 mg•L ^-1; 肝功能示丙氨酸氨基转移酶126 U•L^-1, 天冬氨酸氨基转移酶135 U•L ^-1, 谷氨酰转肽酶82 U•L^-1, 碱性磷酸酶306 U•L^-1, 乳酸脱氢酶404 U•L ^-1, 腺苷脱氨酶29 U•L ^-1, α-羟丁酸脱氢酶271 U•L ^-1; 肾功能、电解质、血糖、免疫球蛋白、补体、AS0、RF、ANA、肝炎免疫、病毒检测（包括麻疹病毒、风疹病毒、EB病毒及巨细胞病毒）, 尿、大便常规均无异常. 心电图示窦性心律, T波改变. 胸部X线片示两肺纹理增多增粗. B超无异常. 诊断为药物超敏反应综合征. 停用美西律, 予甲泼尼龙 80 mg•d ^-1、复方甘草酸苷及氯雷他定等治疗, 红斑丘疹有所消退, 肝酶较前恢复, 病情好转.     

体外人全血热原实验方法研究

目的 建立体外人全血热原实验方法以满足热原检查的需要.方法 分别选择细菌内毒素(LPS)、脂磷壁酸(lipoteichoicacid,LTA)及酵母多糖(zymosan)进行方法 研究,样品于体外与人全血混合孵育,通过检测细胞释放的白细胞介素(interleukin,IL) 1β、IL-6、肿瘤坏死因子α(tumor necrosis factor α,TNF- α)等内热原含量,定量或定性反映样品中所含热原质的量.结果 LPS、LTA和酵母多糖对家兔均有致热活性,最低检测浓度分别为0.5 EU•mL-1,0.5 μg•mL^-1、16 μg•mL^-1.全血法最佳检测指标为IL-1β、孵育时间宜为20 h,人全血 IL-1β法对LPS、LTA、Zymosan最低检测限可以达到0.03 EU•mL^-1,0.25 μg•mL^-1,4.0 μg•mL^-1.通过对合格和不合格样品检测,结果 与BET及家兔法相符合.结论 体外人全血热原实验方法 具有可以标准化、定量的优点,同时可以克服家兔法对边缘产品易造成误判或漏判的缺陷,有很好的应用前景.     

安乃近致暴发性紫癜1例

患儿,男,1岁8个月,因发热半天,皮肤瘀斑2 h入住本院.患儿因发热,家长在私人诊所购买安乃近片,给予患儿1/3片,po,服药后1 h余皮肤出现大片紫斑,哭闹,无呕吐、腹泻,无咳嗽,无抽搐.入院体检：体温 37.8 ℃,呼吸34 次•min^-1,心率124次•min^-1,血压 95/60 mmHg(1 mmHg=0.133 kPa).神志清楚,躯干、臀部及四肢见较多紫癜和瘀斑,面部见散在紫癜.咽红,双侧扁桃体Ⅱ度肿大,充血,无脓栓.口唇及口腔黏膜未见出血点及紫癜.血常规:白细胞18.5×109•L^-1,N 0.729,L0.125,红细胞3.96×1012•L^-1, 血小板236×109•L^-1.肝肾功能、血清电解质、凝血酶原时间、高岭土部分促凝血激酶时间、大小便常规、大便潜血均无异常,心肌酶: 肌酸磷酸激酶143 U•L^-1,肌酸激酶同工酶15 U•L^-1、乳酸脱氢酶340 U•L^-1.入院后给予克林霉素抗感染、地塞米松抗炎、丹参改善微循环,口服双嘧达莫等处理,后体温正常,紫癜处皮肤渐转为暗紫色,但瘀斑处皮肤颜色渐转为黑色并变硬、结痂,考虑出血性坏死,后转上级医院外科进行植皮,术后恢复良好.     

不同厂家苯磺酸氨氯地平片溶出度的考察

目的对不同厂家生产的苯磺酸氨氯地平片进行溶出度考察,评价不同厂家药品的内在质量。方法对光纤溶出法与传统紫外分光光度法进行比较,证明光纤溶出法的可行性,并采用该法对7个厂家生产的苯磺酸氨氯地平片进行实时溶出曲线测定、分析。结果采用单点法来判断7个厂家生产的苯磺酸氨氯地平片的溶出结果,均符合质量标准,但不同厂家生产的苯磺酸氨氯地平片的溶出曲线存在差异。结论不同厂家生产的苯磺酸氨氯地平片质量存在差异,临床用药时应加以注意。     

光纤传感过程分析不同剂型头孢氨苄的溶出度

目的:建立紫外光纤监测头孢氨苄五种固体剂型的溶出度的方法,比较同一药物不同剂型溶出行为差异。方法:采用《中国药典》2010年版中头孢氨苄片溶出度测定方法,结合六通道光纤传感原位过程分析仪原位、在线监测头孢氨苄5种不同固体制剂溶出度。结果:不同剂型头孢氨苄溶出曲线能够反映释药特性,5种剂型释药行为各具特点。结论:光纤药物溶出仪具有实时、在线、过程监测的特点,所得溶出曲线可直观反映不同剂型药物释药特点,为全面评价药物内在质量和临床用药提供参考。     

A comparison of mathematical methods for the determination of in vitro dissolution constants for glass fibers

Biopersistence plays a significant role in determining the potential bioactivity of respirable fibers. In vivo biopersistence in the lung is frequently assessed by in vitro fiber dissolution studies using simulated biological solutions and flow-through techniques. The dissolution rate (k) of a fiber is typically determined by elemental analysis of the flow-through solution to measure the mass of material leached from the fibers over a given time. Various methods may be used to estimate the value of k from these results. The present study compared the in vitro dissolution characteristics of seven experimental glass fiber compositions to those obtained for four recognized fiber compositions (MMVF 10-glass fiber; MMVF 11-glass fiber; MMVF 21-rockwool fiber; crocidolite fiber). Fiber dissolution was examined over a 17-wk period using a flow-through system designed to simulate the conditions encountered by fibers in the extracellular environment of the lung. Mass loss and changes in fiber diameter were determined over time and were then used to calculate k using five different methods. Although the selected methodologies did not produce identical estimations of k for each fiber, the resulting ranking of fiber solubility for each method was consistent. The seven experimental glass fibers were found to have k values intermediate between those of MMVF 11 and MMVF 21.     

Does the preferred orientation of crystallites in tablets affect the intrinsic dissolution?

The aim of this study was to examine the effect of preferred orientation of crystallites, i.e. texture, on the intrinsic dissolution rate of some active pharmaceutical ingredients. Although it has often been speculated that the intrinsic dissolution of pharmaceutical tablets is affected by texture, no experimental evidence of this effect has been reported. The texture of acetylsalicylic acid, tolbutamide, carbamazepine and entacapone tablets was measured using three different methods both before and after the dissolution measurements. To clarify the effect of texture, texturizing and less-texturizing batches of each material were used. The texturizing batches had big needle or plate-like particles and the less-texturizing batches were prepared by grinding the texturizing powders. The USP rotation disc method was used to measure the intrinsic dissolution rate of the samples. The results indicated that the acetylsalicylic acid, tolbutamide and entacapone tablets texturized strongly in compression and the grinding of the texturizing powders decreased the degree of texture. Also the carbamazepine tablets were slightly texturized. All of the texture measurement methods used were found to give acceptable and consistent results and therefore a special texture goniometer is not required to perform these measurements. The intrinsic dissolution rate of all the tablets compacted from the ground powder was slightly higher than the intrinsic dissolution rate of the more texturized samples. However, these differences were not significant on a large scale. After the dissolution tests the degree of texture of the samples was decreased. The intrinsic dissolution rates of the samples were presumably affected by several different parameters such as texture, solubility, pH, surface energetics and crystal strains. Although only small differences were found between the intrinsic dissolution rates of texturized and less texturized samples the effect of texture on the dissolution behavior of the pharmaceuticals should be considered when performing accurate intrinsic dissolution studies.     

A Comparison of Mathematical Methods for the Determination of In Vitro Dissolution Constants for Glass Fibers

Biopersistence plays a significant role in determining the potential bioactivity of respirable fibers. In vivo biopersistence in the lung is frequently assessed by in vitro fiber dissolution studies using simulated biological solutions and flow-through techniques. The dissolution rate (k) of a fiber is typically determined by elemental analysis of the flow-through solution to measure the mass of material leached from the fibers over a given time. Various methods may be used to estimate the value of k from these results. The present study compared the in vitro dissolution characteristics of seven experimental glass fiber compositions to those obtained for four recognized fiber compositions (MMVF 10-glass fiber; MMVF 11-glass fiber; MMVF 21-rockwool fiber; crocidolite fiber). Fiber dissolution was examined over a 17-wk period using a flow-through system designed to simulate the conditions encountered by fibers in the extracellular environment of the lung. Mass loss and changes in fiber diameter were determined over time and were then used to calculate k using five different methods. Although the selected methodologies did not produce identical estimations of k for each fiber, the resulting ranking of fiber solubility for each method was consistent. The seven experimental glass fibers were found to have k values intermediate between those of MMVF 11 and MMVF 21.     

国产与进口尼莫地平片溶出曲线相似性分析

目的采用光纤溶出度分析方法,评价国产与进口尼莫地平片溶出曲线的相似性。方法不同pH值条件下模拟胃肠道环境,采用光纤药物溶出度实时测定仪,在测定波长238 nm处,分别测定国产与进口尼莫地平片的溶出曲线,通过相似因子法比较溶出曲线的相似性。结果在不同pH值条件下测定溶出曲线,通过f2因子比较,7个厂家的尼莫地平片溶出曲线有显著差异。结论光纤药物溶出度仪能准确测定数据,真实地描绘溶出曲线,为改进药品制剂和检测药品质量方面提供真实参考数据。     

A Drug Dissolution Monitor Employing Multiple Fiber Optic Probes and a UV/Visible Diode Array Spectrophotometer

A traditional dissolution pumping system was recently replaced with a fiber optic interface between the spectrometer and the samples. However, the system was limited to a single sample vessel. In this study, a dissolution testing system with six vessels connected to a diode array spectrometer via six optical fibers was investigated. A bifurcated fiber optic bundle was used to transfer the light from the source to the dissolution vessels and was networked so that spectra of each sample can be measured periodically. A full spectrum calibration method based on Principal Component Regression (PCR) was used to determine the concentrations of active ingredients and to account for interferences due to excipients in tablet formulations. Results on this new fiber optic interface system are compared with those obtained previously with the traditional pumping system. Standard errors of prediction are between 1.5 and 3.2% using cross-validation and between 1.1 and 1.7% for the direct validation of two active ingredients in two different drug formulations.     

颅内压监测下尿激酶脑室内灌洗在高血压性脑室内血肿治疗中的策略探讨

目的探讨高血压脑室内出血微创钻孔穿刺置管尿激酶灌洗外引流的临床疗效。方法回顾性分析本院2011年6月~2013年6月收治的高血压性脑室内出血患者52例,根据不同的尿激酶水平和治疗时间,并设立对照组（采用单纯双额骨微创钻孔穿刺置管外引流手术）,记录评估颅内血肿的变化情况、血肿变化与尿激酶灌洗的时间关系、患者日常生活能力（ADL）分级评估、灌洗手术前后GOS评分状况等。结果本组共纳入52例患者,术后3个月,GOS评分5分14例,4分23例,3分15例;ADL分级Ⅰ级14例,Ⅱ级23例,Ⅲ级14例,Ⅳ级1例。与对照组相比,尿激酶脑室内灌洗组在术后颅内压监测、ADL评分、GOS评分等方面具有一定优势。结论高血压脑出血患者出血情况稳定后,早期应用尿激酶治疗组预后相对较好,适当的尿激酶时间剂量组合有助于脑室内出血患者的恢复,颅内压监测下尿激酶脑室内灌洗对高血压脑出血脑室内血肿的治疗效果明显,操作简便、创伤小、安全有效、预后较好。     

过程分析比较5个不同厂家格列吡嗪片的体外溶出相似性

目的通过实时过程监测方法分析5个不同厂家格列吡嗪片在4种溶出介质中的溶出曲线,并采用f2因子对其进行相似性评价。方法不同pH值条件下,采用光纤药物溶出度实时测定仪在222nm处测定波长,测定光程为10mm,分别测定5个不同厂家格列吡嗪片的溶出曲线,通过相似因子f2法评价溶出曲线的相似性。结果不同厂家生产的药品在不同pH值条件下,溶出曲线差异较大。结论实验选用的方法简便、数据真实可靠,可用于区分体外溶出曲线的相似性,为制剂生物等效性实验提供参考数据。     

Estimation of dissolution rate from in vivo studies of synthetic vitreous fibers

Although the dissolution rate of a fiber was originally defined by a measurement of dissolution in simulated lung fluid in vitro, it is feasible to determine it from animal studies as well. The dissolution rate constant for a fiber may be extracted from the decrease in long fiber diameter observed in certain intratracheal instillation experiments or from the observed long fiber retention in short-term biopersistence studies. These in vivo dissolution rates agree well with those measured in vitro for the same fibers. For those special types of fibers, the high-alumina rock wool fibers that could not be measured in vitro, the method provides a way of obtaining a chemical dissolution rate constant from an animal study. The inverse of the in vivo dissolution rate, the fiber dissolution time, correlates well with the weighted half life of long fibers in a biopersistence study, and the in vivo dissolution rate may be estimated accurately from this weighted half-life.