共研磨法提高兰索拉唑的溶出度

采用共研磨法分别制备兰索拉唑与β-环糊精(β-CD)、低取代羟丙纤维素(L-HPC)、羟丙甲纤维素(HPMC)、聚乙烯吡咯烷酮(PVP)、交联聚维酮(PVPP)、聚乙二醇(PEG)6000或壳聚糖(1:1)的共研磨物,测定了原药、物理混合物和共研磨物的溶出度,并用差示扫描量热法和X-射线衍射法鉴别药物在共研磨物中的存在状态.测定了兰索拉唑原药、物理混合物和共研磨物于室温放置6个月后的含量和溶出度,考察共研磨样品的稳定性.结果表明,兰索拉唑与β-CD、L-HPC、HPMC、PVP和壳聚糖的共研磨物的溶出度较兰索拉唑原药有显著提高,且稳定性较好.     

Proton pump inhibitors omeprazole, lansoprazole and pantoprazole induce relaxation in the rat lower oesophageal sphincter

Objectives We aimed to investigate effects of the proton pump inhibitors (PPIs) omeprazole, lansoprazole and pantoprazole, which are currently used for the treatment of hyperacidity and gastro‐oesophageal reflux, on the reactivity of the isolated rat lower oesophageal sphincter. Methods Omeprazole, lansoprazole and pantoprazole (all 10^–9–10^–3m , cumulatively) were tested on carbachol‐induced (10^–6m ) contraction. In addition, the effects of PPI preincubation (all 10^–3m ) on the contractions induced by cumulative carbachol (10^?9–10^?5m ), angiotensin‐2 (10^?9–10^–5m ) or electrical field stimulation (EFS; 40 V, 32 Hz, 1 ms, 10 s) were assessed. Finally, the effects of PPI on the spontaneous contractile activity of the tissue were also evaluated. Key findings PPI relaxed precontracted lower oesophageal sphincter in a concentration‐dependent manner and suppressed carbachol‐, angiotensin‐ and EFS‐induced contractions. Furthermore, PPI attenuated spontaneous contractile activity of the tissue. Conclusions Omeprazole, lansoprazole and pantoprazole had a suppressor effect on lower oesophageal sphincter contractions.     

兰索拉唑和泮托拉唑治疗十二指肠溃疡出血的最小成本分析

目的：考察兰索拉唑和泮托拉唑治疗十二指肠溃疡并出血患者临床疗效,并对两种治疗方案进行最小成本分析。方法：将60例十二指肠溃疡并出血的患者按照治疗方案,分为兰索拉唑治疗组30例,泮托拉唑治疗组30例,2组均未使用其他抑制胃酸分泌的药物。观察2组的临床疗效,不良反应发生率,并进行经济学分析。结果：2组治疗方案的临床有效率分别为93.33%和96.67%,无统计学意义。不良反应发生率经检验后亦无统计学意义（P>0.05）,因此采用最小成本分析法进行经济学评价。兰索拉唑治疗组和泮托拉唑治疗组的成本分别为11 611.60元、13 445.09元。结论：兰索拉唑和泮托拉唑治疗十二指肠溃疡并出血症状疗效和安全性均较好,但相较于泮托拉唑,使用兰索拉唑治疗成本更低、经济性更好,临床可根据患者实际情况选择用药。     

注射用兰索拉唑的安全性评价

目的 评价国产注射用兰索拉唑的安全性。方法 将注射用兰索拉唑配成适当浓度,观察豚鼠静脉注射后有无过敏反应、家兔静脉注射有无血管刺激性及热原反应、体外溶血试验中是否具有溶血和血球凝集作用,小鼠静脉注射的急性毒性。结果 豚鼠静脉注射兰索拉唑无过敏反应,家免静脉注射兰索拉唑无血管刺激性及热原反应,体外溶血试验无溶血和血球凝集作用,小鼠静脉给药的LD50及95％的可信限为163.8mg/kg和150．7～178．0mg／kg。结论 该药可供静脉注射试用给药。     

灭Hp胶囊多联治疗Hp阳性消化性溃疡

目的寻求中西医结合治疗Hp相关性消化性溃疡(PU)的理想方案方法采用前瞻性、随机双盲、安慰剂对照研究Hp阳性的PU患者93例被随机分为4组A组(新三联)达克普隆30mg,1次/d+阿莫西林500mg,2次/d+克拉霉素250mg,2次/d,连服10 d;B组(灭Hp胶囊四联)新三联10d+灭Hp胶囊6粒,2次/d,连服28 d;C组(灭Hp胶囊三联)达克普隆30 mg,1次/d+克拉霉素250 mg,2次/d,连服10 d,+灭Hp胶囊6粒,2次/d,连服28 d,D组(安慰剂)胃舒平3片,2次/d,连服28 d.双盲双模拟用药.结果 Hp根治率在B,C组与A组分别为96%,92%和92%;溃疡愈合率分别为100%,92%和88%,三组间差异无显著性,明显高于D组的HP根治率(0%)和溃疡愈合率(20%)(均P＜0.01).B,C组溃疡愈合质量明显优于D组,也优于A组B,C组治疗后胃粘膜磷脂(mg/g,93±26.92±27)、氨基己糖(mg/g,55±20,53±15)和血清表皮因子(EGF)(μg/L,0.7±0.3,0.6±0.4)含量明显高于治疗前磷脂(mg/g,79±23,81±23,均P＜0.01)、氮基己糖(mg/g,40± 14;42±16,均P＜0.01)和EGF(μg/L,0.5±0.2,P＜0.01;0.5±0.3,P＜0.05)含量.A组治疗后仅氨基己糖含量(49 ± 18)高于治疗前(42±16,P＜0.05),磷脂和EGF无明显变化.D组磷脂、氨基已糖和EGF治疗前后无明显变化(P＞0.05)各项检测指标B组优于C组,但无统计学意义治疗期间患者依从性好,无不良反应发生.结论中西医结合灭Hp胶囊三联、四联疗法除了有Hp根除与溃疡愈合率高,而乏副作用外,还具有保护胃粘膜,溃疡愈合质量高的特点,是治疗Hp相关性PU的较为理想方案.     

注射用兰索拉唑在中国人体内的药动学研究

 目的 建立人血浆中兰索拉唑的反相高效液相色谱紫外检测法,进行兰索拉唑的人体药动学研究。方法 血浆样品以乙醚提取,非那西丁为内标,采用Kromasil100-5 C₈(4.6 mm×150 mm)色谱柱,以水-乙腈-二乙胺（用磷酸调pH 6.7）（600∶400∶1.2）溶液为流动相,流速0.8 mL·min-1,柱温40 ℃,检测波长285 nm。12名健康受试者,男女各半,采用随机开放自身对照三交叉,单剂量静脉滴注低（15 mg）或中 (30 mg) 或高 (60 mg) 剂量的注射用兰索拉唑,测定血浆中兰索拉唑浓度,计算兰索拉唑的人体药动学参数,并对其进行统计分析。结果 线性范围49.0~4 900.0 ng·mL-1,最低定量限为49.0 ng·mL-1（S/N > 10）,方法学回收率为93.3％～100.1％,提取回收率大于82％。15 mg剂量组主要药动学参数：ρ_max为（1 105.65±506.24）ng·mL-1,t_max 为（0.24±0.14）h,t_1/2为（3.01±1.77）h, MRT_0-12为（0.93±0.95）h,AUC_0-12为（991.16±814.49）ng·h ·mL-1;30 mg剂量组,ρ_max为（2 171.33±799.02）ng·mL-1,t_max 为（0.51±0.16）h,t_1/2为（3.98±2.51 ）h, MRT_0-12为（1.91±0.83）h,AUC_0-12为（3 495.87±1 770.92）ng·h ·mL-1; 60 mg剂量组,ρ_max为（4 070.53±643.04）ng·mL-1,t_max 为（1.02±0.07）h,t_1/2为（3.73±1.55）h,MRT_0-12为（2.42±0.65）h,AUC_0-12为（8 351.14±2 599.90）ng·h ·mL-1。结论 本法简便、灵敏、重现性好。健康受试者静脉滴注15、30、60 mg兰索拉唑后,其体内药动学过程基本上呈现线性动力学特征而无饱和性,血浆药物浓度-时间曲线符合二室模型。     

质子泵抑制剂致过敏性休克84例文献分析

目的 探讨质子泵抑制剂致过敏性休克的规律及特点,为其临床合理应用提供依据。方法 检索中国知网总库、万方数据总库、维普网、中国生物医学文献服务系统和PubMed、Web of Science数据库收录的1990—2022年间发表的质子泵抑制剂致过敏性休克相关案例报道文献,对符合要求的病例进行统计和分析。结果 共收集到82篇文献,共计84例质子泵抑制剂致过敏性休克。男女比例约为1∶1,以41～60岁和61～80岁患者居多,均占36.47%;具有食物或药物过敏史者占28.57%;共涉及5种药物,奥美拉唑、泮托拉唑、兰索拉唑分别位居前3位,占90.49%;以静脉方式给药的发生率最高,占60.71%;主要发生于首次用药,用药60 min内,占78.57%,其中最快为用药后几秒钟;主要临床表现为血压下降、大汗淋漓、心率加快、皮肤瘙痒、皮疹等;预后良好;不同的质子泵抑制剂间可能存在交叉过敏。结论 多种质子泵抑制剂均可引起过敏性休克,应引起广大医务工作者的关注,加强用药监护,保证患者用药安全。     

Determination of R(+)- and S(–)-Lansoprazole Using Chiral Stationary-Phase Liquid Chromatography and Their Enantioselective Pharmacokinetics in Humans

Purpose. Stereoselective and sensitive methods employing chiral stationary phase columns for HPLC determination of enantiomers of lansoprazole in the human serum were developed and pharmacokinetic behaviors of the enantiomers were evaluated in seven subjects. Methods. Five chiral stationary phase columns: Chiralcel OD (cellulose tris(3,5-dimethyl-phenylcarbamate)), OF (cellulose tris(4-chloro-phenylcarbamate)), OG (cellulose tris(4-methylphenylcarbamate)) and OJ (cellulose tris(4-methylbenzoate)), and Chiralpak AS (amylose tris ((S)-1 -phenylethylcarbamate)) were investigated. Results. Chiralcel OD and Chiralpak AS columns gave a good resolution of R(+)- and S(–)-enantiomers from racemic lansoprazole, but Chiralcel OF, OG, and OJ did not. The mean C_max and the AUC values of R(+)-enantiomer were 3–5 times greater than those of S(–)-enantiomer following oral administration of 30 mg of racemic lansoprazole. The CL_tot values of R(+)-enantiomer were significantly smaller than those of S(–)-enantiomer. Binding of R(+)-enantiomer to human serum proteins was significantly greater than that of S(–)-enantiomer. The mean metabolic ratio (metabolites/parent compound) in human liver microsomes of S(–)-enantiomer was significantly greater than that of R(+)-enantiomer. Conclusions. The stereoselective pharmacokinetics of lansoprazole enantiomers is likely due to its Stereoselective protein binding and/ or metabolism.     

Lansoprazole reduces preoperative gastric fluid acidity and volume in children

The purpose of this study was to explore the efficacy of lansoprazole, a proton pump inhibitor, in reducing the acidity and volume of gastric aspirate in children immediately following the induction of anaesthesia. One hundred healthy in-patients aged 3–11 yr undergoing elective surgery were randomly allocated to four groups (n = 25 each): lansoprazole-lansoprazole, placebo-placebo, placebo-lansoprazole, and lansoprazole-placebo. For each treatment regimen, the first medication was administered at 9:00 pm on the night before surgery and the second at 5:30 am on the morning of the day of surgery (three hours preoperatively). The dose of lansoprazole was 30 mg (approximately 1.4 mg · kg^?1 mean). Children were offered 10 ml · kg^?1 apple juice three hours before induction of anaesthesia. After induction of anaesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube and analyzed for pH and total fluid volume. Lansoprazole increased gastric fluid pH and decreased gastric fluid volume regardless of whether it was administered before or after placebo. Two consecutive doses of lansoprazole was the most effective means of increasing the pH and reducing the volume of gastric aspirate; in this group, there were no subjects with gastric aspirate volume >0.4 ml · kg^?1 and pH <2.5. Oral lansoprazole, at least 30 mg, given on the night before surgery or on the morning of surgery will improve the gastric environment at the time of induction of paediatric anaesthesia. The most effective regimen was two doses (at bedtime and on the morning) of lansoprazole.