【摘要】 目的评价牛磺熊去氧胆酸胶囊(滔罗特Taurolite)对胆囊胆固醇结石的溶石效果与安全性。方法2003年10月~2004年12月,对滔罗特胶囊(含牛磺熊去氧胆酸250 mg)进行随机双盲、安慰剂对照、多中心的临床研究。受试者为体检查出,无症状或仅有轻度饭后上腹饱胀不适,结石<2 cm,胆囊有功能的胆固醇结石患者。所有符合入选条件的患者填写知情同意书后随机分入试验组与对照组,进入4个月的双盲期。试验组应用滔罗特胶囊1粒/次,3次/日,对照组应用安慰剂胶囊1粒/次,3次/日。每2个月复查B超,口服胆囊造影(OCG),血常规与肝肾功能检查,以对滔罗特有效性和安全性进行评估。4个月时揭盲,对照组终止试验,试验组继续服药2个月(疗程6个月)。疗效评估按国际统一标准:全溶(completedissolution,CD),OCG示结石充盈缺损全部消失,B超示胆囊无异常回声;大部分溶(greater part dissolution,GPD),OCG和B超示结石的数目或直径或总体积减少50%以上;部分溶(partial dissolution,PD),OCG和B超示结石的数目或直径或总体积减少<50%;无效(no change,NC),OCG和B超均示结石的数目或直径或总体积没有明显的变化。CD+GPD为显效,CD+GPD+PD为有效。结果两中心共纳入123例受试者,其中试验组64例,对照组59例。试验期间脱落和退出试验11例(8.9%),其中试验组2例,对照组9例。112例完成疗程和观察,其中试验组62例,对照组50例。①滔罗特4个月时显效率27.4%(17/62),有效率56.5%(35/62);6个月时显效率41.9%(26/62),有效率67.7%(42/62)。对照组4例(8.0%)有溶石反应,46例无效。2组疗效差异有显著性(χ2=28.678,P=0.000)。②试验期间无严重不良事件发生,2组在试验期间共出现不良反应4例,试验组3例(4.8%,3/62),对照组1例(2.0%,1/50)。2例与服用药物有关,药物不良反应发生率1.8%(2/112)。③试验组服药前与服药后2、4个月后血常规与肝肾功能7项生化指标(ALT、AST、ALP、TBil、ALB、Cr、BUN)的变化比较均无显著性差异(P>0.05)。血常规与肝肾功能7项生化指标的变化与服用滔罗特无关。④试验组与对照组比较,服药2、4个月时血常规与肝肾功能7项生化指标均无显著性差异(P>0.05)。血常规与肝肾功能7项生化指标的变化与服用滔罗特无关。结论滔罗特为治疗胆囊胆固醇结石安全有效的药物。更多还原

【Abstract】 Objective To evaluate the safety and therapeutic efficacy of tauroursodeoxycholic acid(Taurolite) for dissolution of cholesterol stones in gallbladder.Methods From October 2003 to December 2004,a multicenter double-blind randomized-controlled trial of Taurolite(containing tauroursodeoxycholic acid 250 mg) for dissolution of cholesterol gallstones in gallbladder was carried out.All the subjects were the asymptomatic patients or patients with mild epigastric flatus,whose diagnosis of cholecystic radiolucent stones in the functioning gallbladder was confirmed by B-ultrasonography and oral cholecystography(OCG).The maximum diameter of the stones was less than 2 cm.Each patient was informed as to the aims of the experiment and gave his consent(underwrited consent).All the subjects were randomly divided into both experimental(E) and control(C) groups.One capsule of Taurolite was given to the E group,while placebo(in the same capsule without tauroursodeoxycholic acid) was given to the C group.B-ultrasonography,OCG,blood routine(count of white blood cells,red blood cells,blood platelet,and haemoglobin),hepatic function(alanine aminotransferase,ALT;aspartate aminotransferase,AST;alkaline phosphatase,ALP;total bilirubin,TBil;and albumin,ALB;) and kidney function(urea nitrogen,BUN and creatine,Cr;) tests were carried out before and every two months after the treatment to evaluate the side-effect and therapeutic efficacy of Taurolite.The blind answer was revealed at the fourth month.The experiment was stopped in the C group at the fourth month,but was continued for another two months(total experimental time was 6 months) in the E group in order to have enough time for stone-dissolution.Therapeutic efficacy was evaluated by examining number and size of the gallstones by B-ultrasonography and OCG.Criteria of therapeutic efficacy were as follows: complete dissolution(CD): disappearance of gallstones;greater part dissolution(GPD): more than 50% decrease(number or size);partial dissolution(PD): less than 50% decrease(number or size);No change(NC): unchanged or increased number or size of the stones.CD+GPD was considered as prominent efficacy,CD+GPD+PD was considered as effective.Results A total of 123 patients,including 64 patients in E group and 59 patients in C group,were enrolled into this trial.During the experiment,11 cases(2 in E group and 9 in C group) withdrew from the trial.The seceding ratio was 8.9%.112 cases(62 in E group and 50 in C group) completed the experiment.There was no statistical difference between E and C groups in the distribution of sex,age,and number and size of stones(t test or χ2 test,P>0.05).Both the groups were comparable.(1) Prominent rate of therapeutic efficacy(CD+GPD) at the fourth month for Taurolite was 27.4%(17/62),and the effective rate(CD+GPD+PD) was 56.5%(35/62).Prominent rate at the sixth month for Taurolite was 41.9%(26/62),and the effective rate was 67.7%(42/62).In the C group,4 cases(8.0%) showed dissolution response and 46 had NC.A significant difference was seen between the two groups(χ2=28.678,P=0.000).(2) No severe adverse event occurred.Four patients had adverse events [3(4.8%) in E group and 1(2.0%) in C group].The symptom of 2 cases might be related to the drug,the rate of drug-related adverse events was 1.8%(2/112).(3) No significant difference existed between pre-treatment and the 2nd and 4th month after the treatment in blood routine,and hepatic and kidney function tests(ALT,AST,ALP,TBil,ALB,Cr,BUN) in E group(P>0.05).The changes in blood routine,and hepatic and kidney functions were not related to the amount of Taurolite taken.(4) Compared with the control group,no significant difference existed in blood routine,hepatic and kidney function test between pre-treatment and the 2nd,4th month after treatment in the E group(P>0.05).The changes in blood routine,and hepatic and kidney functions were not related to Taurolite.Conclusion Taurolite is a safe and effective drug for the treatment of cholesterol stone in gallbladder.更多还原