反相离子对高效液相色谱法分离甲磺酸加贝酯有关物质及其含量测定

建立蛋白酶抑制剂甲磺酸加贝酯原料药的有关物质分离检测及其含量测定方法。采用反相离子对色谱法,色谱柱为ODS柱;流动相为乙腈 辛烷磺酸钠缓冲液(pH 值 3.5)(40∶60),流速为1.0 ml/min;含量检测波长为236 nm,有关物质检测波长为258 nm。以此建立的色谱方法使有关物质与主药分离良好,甲磺酸加贝酯在12.5~125.0μg/ml内线性关系良好,平均回收率为99.75%,RSD为0.6%。方法简便、准确,可用于甲磺酸加贝酯有关物质的检查及含量测定。     

生长抑素联合加贝酯治疗重型急性胰腺炎

目的观察生长抑素联合加贝酯治疗重型急性胰腺炎的疗效。方法选取我院重型急性胰腺炎患者53例,分为单用生长抑素组、生长抑素联合加贝酯组、生长抑素联合乌司他丁组。观察血清淀粉酶、白细胞、血糖、血钙恢复时间及腹痛、上腹部压痛缓解时间的指标差异。结果生长抑素联合加贝酯组、生长抑素联合乌司他丁组以上指标恢复时间均短于单用生长抑素组,P<0.05。生长抑素联合加贝酯组白细胞恢复时间短于生长抑素联合乌司他丁组(P<0.05),而其他指标两组比较差异无统计学意义(P>0.05)。结论应用生长抑素联合加贝酯、生长抑素联合乌司他丁治疗重型急性胰腺炎较单独应用生长抑素效果好。生长抑素联合加贝酯组白细胞恢复时间较生长抑素联合乌司他丁组短,而两组在血清淀粉酶、血糖、血钙恢复时间及腹痛、上腹部压痛缓解时间的指标上无明显差异。     

加贝酯预防内镜逆行胰胆管造影术后胰腺炎的实验研究

背景：急性胰腺炎是内镜逆行胰胆管造影术（ERCP）的常见并发症，加贝酯对ERCP术后胰腺炎的预防作用仍存在争议。目的：探讨加贝酯对大鼠ERCP术后胰腺炎的预防作用。方法：通过血压计传导50mmHg（1mmHg=0.133kPa）的恒定压力，向胰胆管内注入30％泛影葡胺，以制备SD大鼠ERCP术后胰腺炎模型。检测各组血清淀粉酶水平，并行胰腺组织病理学检查。结果：加贝酯治疗组的血清淀粉酶水平和胰腺组织炎症评分均显著低于胰腺炎对照组（P〈0.05）。结论：加贝酯静脉滴注对预防ERCP术后胰腺炎有效。     

Pharmacological approach to acute pancreatitis

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis （AP） based on experimental animal models and clinical trials. Somatostatin （SS） and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis （PEP）. The protease inhibitor Gabexate mesilate （GM） is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin （NGL） is a nitrogen oxide （NO） donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs （NSAID） indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 （IL-10） is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha （TNF-α） have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta- lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.     

加贝酯对Oddi括约肌运动的影响

目的　观察加贝酯对Oddi括约肌运动功能的影响。方法　对我院 12例行内镜下逆行胰胆管造影 (ERCP)患者于内镜下作Oddi括约肌测压术 ,记录Oddi括约肌的基础压、基础收缩幅度、收缩频率和运动指数 (基础收缩幅度×收缩频率 ) ,并在静脉滴注加贝酯 1、3mg·kg-1·h-1前后 ,分别重复以上测压过程。以用药前后记录数据作自身对照配对t检验进行统计学处理。结果　①静脉滴注加贝酯1、3mg·kg-1·h-1不影响Oddi括约肌的基础压 (P >0 .0 5 )和基础收缩幅度 (P >0 .0 5 )。②加贝酯能明显减少Oddi括约肌的收缩频率 (P <0 .0 5 ) ,但用药剂量 1、3mg·kg-1·h-1之间差异无显著性 (P >0 .0 5 )。③大剂量加贝酯可明显降低Oddi括约肌运动指数 (P <0 .0 1) ,且 3mg·kg-1·h-1与 1mg·kg-1·h-1剂量间差异也有显著性 (P <0 .0 5 )。结论　加贝酯能减少人Oddi括约肌的收缩频率 ,3mg·kg-1·h-1时还能降低运动指数。加贝酯对Oddi括约肌运动的影响可解释加贝酯减少ERCP后胰腺炎的发生。     

加贝酯预防ERCP术后胰腺炎的Meta分析

目的评价加贝酯预防内镜逆行胰胆管造影术后胰腺炎(post-ERCP pancreatitis,PEP)的安全性和有效性。方法计算机检索Cochrane图书馆(1970～2010年12月)、PubMed(1966～2010年12月)、EMBASE(1966～2010年12月)及中国生物医学文献数据库(1978～2010年12月),查找加贝酯预防PEP的随机对照试验及其参考文献。由2名研究者独立选择试验、提取资料和评估方法学质量,采用Cochrane协作网提供的RevMan 4.2软件进行统计分析。结果共有11篇文献,包括3 012例患者纳入本研究。Meta分析结果显示:与安慰剂比较,持续(≥12 h)大剂量(≥1 000 mg)使用加贝酯可以有效预防PEP的发生(OR=0.27,95%CI为0.11～0.64,P=0.003),并可以有效预防ERCP术后腹痛的发生(OR=0.44,95%CI为0.25～0.79,P=0.005)。快速(≤6.5 h)小剂量(≤500 mg)使用加贝酯并不能有效预防PEP的发生(OR=0.85,95%CI为0.59～1.34,P=0.570),不能预防ERCP术后高淀粉酶血症的发生(OR=0.86,95%CI为0.69～1.07,P=0.180),也不能有效地预防ERCP术后腹痛的发生(OR=0.66,95%CI为0.32～1.35,P=0.250)。加贝酯组与乌司他丁组比较,2组对PEP预防效果的差异无统计学意义(OR=1.57,95%CI为0.39～6.24,P=0.520),对ERCP术后高淀粉酶血症预防效果的差异也无统计学意义(OR=1.85,95%CI为0.83～4.13,P=0.130)。结论持续(≥12 h)大剂量(≥1 000 mg)使用加贝酯能够预防PEP以及ERCP术后腹痛的发生,对于ERCP术后高淀粉酶血症的预防也有一定效果。加贝酯与乌司他丁对PEP和ERCP术后高淀粉酶血症的预防效果相同。上述结论尚需多中心、大样本和长期随访的高质量随机对照研究证实。     

A retrospective comparative study of recombinant human thrombomodulin and gabexate mesilate in sepsis-induced disseminated intravascular coagulation patients

The novel biological agent recombinant human thrombomodulin (rhTM) has been used clinically in Japan to treat disseminated intravascular coagulation (DIC) since 2008. Previous studies have shown the efficacy of rhTM versus heparin therapy or non-rhTM therapy. We retrospectively evaluated and compared the efficacies of rhTM and gabexate mesilate (GM) in patients diagnosed with sepsis-induced DIC. From September 2010 to October 2012, patients with sepsis-induced DIC who were treated with rhTM (n = 13) or GM (n = 10) at Nagasaki Municipal Hospital were extracted. Patients receiving other anticoagulants in combination were excluded. Clinical information, laboratory data, Sequential Organ Failure Assessment (SOFA) scores, and DIC scores were obtained from the medical records. Mortality at days 7 and 30 after DIC diagnosis and changes in laboratory data and SOFA scores from days 1–7 were evaluated. The groups' clinical characteristics did not differ, except for the relatively higher C-reactive protein (CRP) levels in the rhTM group (P = 0.0508). The survival rates of the rhTM and GM groups on days 7 and 30 were 92.3%, 69.2% and 80%, 70%, respectively, both group indicated similar mortality. However, on day 7, the platelet counts, SOFA scores, and CRP levels significantly improved in the rhTM group; the platelet counts and SOFA scores did not improve significantly in the GM group. The platelet counts of the rhTM group significantly improved compared to the GM group (P = 0.004). Recombinant human thrombomodulin might be more effective for sepsis-induced DIC than GM.     

水胶体敷料防治加贝酯致静脉炎效果观察

目的 探索水胶体敷料对静脉输注加贝酯致静脉炎的防治效果.方法 将2013年1～8月我院消化内科96例静脉输注加贝酯的患者随机分为实验组62例和对照组34例,实验组采用水胶体敷料固定留置针,对照组采用无菌医疗固定贴膜固定,比较两组间静脉炎的发生差异.结果 对照组与实验组的静脉炎发生率分别为82.3%、11.3%,P＜0.01.结论水胶体敷料能很好地防治加贝酯致静脉炎,效果颇佳.