熊去氧胆酸联合胆维他与山莨菪碱治疗环孢素性肝损害比较

目的 观察熊去氧胆酸片联合胆维他片及单独山莨菪碱治疗肾移植术后环孢素性肝损害的疗效,寻找有效的治疗方法.方法 将肾移植术后28例环孢素性肝损害患者分为两组,A组:口服熊去氧胆酸片50 mg,tid胆维片25 mg,tid;B组:山莨菪碱40 mg加入5%葡萄糖注射液中,每天一次静点或10 mg每日4次口服,疗程1～3个月.结果 A组16例中有15例治愈(占93.8%),1例好转(占6.3%);B组12例中3例好转(25.0%),9例无效(占75.0%).结论 熊去氧胆酸与胆维他联合应用肾移植术后环孢素所致肝损害疗效明显优于山莨菪碱.     

护肝片与熊去氧胆酸联合治疗肾移植后药物性肝损害

目的：评价护肝片与熊去氧胆酸联用对肾移植后药物性肝损害的疗效。方法：50例肾移植术后肝功能异常的患者,口服护肝片4片,tid,熊去氧胆酸1－2片,itd,疗程为1－3个月,必要时停用Aza,结果：有29例（58％）,治愈。13例（26％）好转,8例（16％）无效,肝功能异常患者治疗前后血清TBiol,DBiol,IBiol,CsA浓度均有显著性差异（P＜0．01,P＜0．01,P＜0．01,P＜0．05）,而其肾功能无明显变化。结论：护肝片与熊去氧胆酸联合应用对肾移植后药物性肝损害有一定的疗效。     

护肝片与熊去氧胆酸联合治疗肾移植后药物性肝损害

目的评价护肝片与熊去氧胆酸联用对肾移植后药物性肝损害的疗效.方法50例肾移植术后肝功能异常的患者,口服护肝片4片,tid,熊去氧胆酸1～2片,tid.疗程为1～3个月.必要时停用硫唑嘌呤.结果有29例(58%)治愈,13例(26%)好转,8例(16%)无效.肝功能异常患者治疗前后血清TBiol、DBiol、IBiol、CsA浓度均有显著性差异(P<0.01,P<0.01,P<0.01,P<0.05),而其肾功能无明显变化.结论护肝片与熊去氧胆酸联合应用对肾移植后药物性肝损害有一定的疗效.     

熊去氧胆酸治疗胆汁淤积性肝炎疗效观察

目的探讨熊去氧胆酸治疗胆汁淤积性肝炎的临床疗效。方法选择笔者所在医院2009年1月～2012年1月收治的胆汁淤积性肝炎患者80例,随机分为治疗组和对照组各40例。对照组采用综合保肝疗法(肌苷、甘力欣、维生素C等),治疗组在此基础上加用熊去氧胆酸,4周为1疗程。结果治疗组总有效率为80.0%,明显优于对照组47.5%,差异有统计学意义(P<0.05)。治疗前后患者的TBIL、ALT、ALP及AST四项肝功能指标较治疗前有明显改善(P<0.05);且治疗组的各项指标下降水平显著优于对照组(P<0.05)。结论运用熊取胆汁酸治疗胆汁淤积性肝炎具有显著疗效,患者的肝功能指标可恢复到正常水平,且不良反应少,可进一步推广应用。     

熊去氧胆酸联合地塞米松治疗妊娠期肝内胆汁淤积症的疗效观察

目的探讨熊去氧胆酸联合地塞米松治疗妊娠期肝内胆汁淤积症的临床疗效。方法将我院2010年8月至2012年12月间收治的104例妊娠期肝内胆汁淤积症患者随机分为治疗组和对照组,每组各52例,对照组患者给予单纯地塞米松治疗,治疗组患者在此基础上加用熊去氧胆酸治疗,比较两组患者的临床疗效。结果两组患者治疗后的ALT、AST及TBA水平较治疗前均有显著改善,差异有统计学意义(P<0.05),治疗组患者各项指标改善情况优于对照组患者,组间差异有统计学意义(P<0.05)。结论采用熊去氧胆酸联合地塞米松治疗妊娠期肝内胆汁淤积症临床疗效确切,能够显著改善患者的临床症状,保证母婴安全,值得临床进一步推广使用。     

强肝胶囊联合熊去氧胆酸治疗慢性乙型肝炎的临床分析

乙肝是我国乃至世界范围内的高发疾病之一,其不仅给患者带来学习、就业的潜在不利影响,而且部分患者还可能进展成为肝硬化、肝衰竭、肝癌等严重疾病,威胁患者生命[1]。由于乙肝病程漫长,很难在短期内彻底根治,因此我们引入中药治疗的理念,采用中西医结合疗法,联合使用强肝胶囊和熊去氧胆酸,取得较好效果,报告如下。     

熊去氧胆酸治疗妊娠期肝内胆汁淤积症的研究进展

熊去氧胆酸(UDCA)主要通过3种机制治疗胆汁淤积性肝病：①肝细胞保护作用；②刺激肝胆分泌；③免疫调节作用。采用UDCA治疗妊娠期肝内胆汁淤积症（ICP），不仅可以改善患者临床、生化指标，而且可以改善孕妇产后临床结局。将其广泛应用于ICP，仍需积累临床资料。UDCA有可能成为治疗ICP的一个较有前途的药物。     

熊去氧胆酸的药理作用

<正> 熊去氧胆酸(3α,7β-二羟基-5β-胆烷酸、UDCA)是中药熊胆的有效成分。1927年日本正田氏从熊胆汁中首次分离出纯结晶,1957年合成成功并作为利胆剂用于临床。1973年日本发现UDCA有溶解胆结石的作用,且具有毒性小、剂量小的优点,从而引起世界各国的关注。日本药局方第10版已收载本品,用于胆石症及急、慢性肝炎、胆囊炎、胆管炎等疾病的治疗。本文简述其药理研究的进展。对胆汁分泌的作用张文忠等报道,给用乌拉坦麻醉的雄性大鼠口服UDCA 100mg/kg,用胆道插管法实验,发现UDCA有明显的利胆作用并能增     

S-腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症的疗效观察

目的观察思美泰联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy．ICP）的疗效。方法选择60例ICP患者．随机分为观察组（30例）和对照组（30例）两组。观察组联用思美泰与熊去氧胆酸治疗10d,对照组单用熊去氧胆酸治疗10d。治疗前后分别检测两组患者血清总胆酸（TBA）、总胆红素（TB）、谷丙转氨酶（ALT）和谷草转氮酶（AST）,并进行瘙痒评分;评价两组患者妊娠结局。结果两组患者治疗无瘙痒评分、TBA、TB、ALT、AST的水平均较治疗前降低（P〈0．01）;观察组治疗后瘙痒评分、TBA、TB、ALT、AST的水平较对照组下降明显,差异有显著性意义（P〈0．05）。妊娠结局：两组羊水污染率、早产率、新生儿窒息率及新生儿体重差异有境计学意义（P〈0．01）。结论思美泰联合熊去氧胆酸是治疗ICP安全有效方法．可改善妊娠预后。     

熊去氧胆酸治疗肝内胆汁淤积症临床观察研究

目的对比观察应用熊去氧胆酸（UDCA）治疗肝内胆汁淤积症的疗效及安全性。方法连续收集该院199例肝内胆汁淤积患者,分为UDCA治疗组与常规保肝药对照组,比较二组治疗前后症状体征和肝生化指标的改善程度。结果UDCA组显效63例,有效48例,无效26例,总有效率为81.02%;对照组显效18例,有效24例,无效20例,总有效率为67.74%。熊去氧胆酸能显著改善患者的肝功能生化指标,其中总胆红素、结合胆红素、r-谷氨酰转移酶下降幅度高于对照组（P〈0.05）。治疗观察期间,两组均未见严重不良反应。结论熊去氧胆酸在对肝内胆汁淤积性肝病患者住院治疗期间疗效较满意,安全性良好。     

RP-HPLC法测定熊去氧胆酸胶囊中熊去氧胆酸及有关物质的含量

目的建立反相高效液相色谱法(RP-HPLC)测定熊去氧胆酸胶囊中熊去氧胆酸、胆酸、鹅去氧胆酸及胆石酸的含量。方法使用Diamonsil C18色谱柱(200 mm×4.6 mm,5μm),流动相为乙腈-0.03 mol·L-1磷酸溶液(体积比为40∶60),流速为1.4 mL·min-1,检测波长为205 nm,柱温为35℃。结果熊去氧胆酸胶囊中熊去氧胆酸、胆酸、鹅去氧胆酸及胆石酸在25 min内洗脱并基线分离。熊去氧胆酸、胆酸、鹅去氧胆酸及胆石酸的线性范围分别为0.80²00.00、0.45200.00、0.45¹10.00、0.30110.00、0.30⁷0.00和0.3070.00和0.30⁸0.00 mg·L-1,平均回收率分别为99.7%、99.3%、98.7%和99.1%,RSD分别为1.30%、1.47%、1.87%和1.95%(n=3)。结论 RP-HPLC可用于同时测定熊去氧胆酸胶囊中熊去氧胆酸、胆酸、鹅去氧胆酸及胆石酸的含量,可应用于熊去氧胆酸胶囊胶囊制剂的质量控制。     

Pharmacokinetics of ursodeoxycholic acid in rat

The pharmacokinetic behaviour and metabolism of ursodeoxycholic acid (UDCA) have been studied in the rat. After oral administration of both 3H-labelled (4 muCi/kg body wt) and unlabelled (20 mg) UDCA, UDCA appeared in serum almost entirely in conjugated form (taurine conjugated); UDCA was present in bile mostly as taurine conjugated; the more relevant metabolite is 3 alpha,6 alpha, 7 beta-trihydroxycholanoic acid which represents 10% of the total bile acid pool. UDCA increased bile flow and selectively decreased biliary cholesterol secretion, while phospholipid secretion was unaffected. Faecal UDCA excretion was 15-20% while the urinary extraction was 1.5% during 24 h. The data show that UDCA, when administered in high dose, is promptly secreted into bile almost entirely metabolized to tauroursodeoxycholic acid, where it (1) desaturates the cholesterol in bile, (2) exerts choleretic properties.     

Pharmacological treatment of biliary cirrhosis with ursodeoxycholic acid

Importance of the field: Primary biliary cirrhosis is a cholestatic liver disease that at one time was the leading indication for liver transplantation. Treatment with ursodeoxycholic acid has clearly improved the natural history of primary biliary cirrhosis.

Areas covered in this review: The treatment of primary biliary cirrhosis with a focus on ursodeoxycholic acid is covered. Papers related to treatment of primary biliary cirrhosis and associated conditions, using a variety of drugs but with a focus on ursodeoxycholic acid, are included. The papers reviewed date from 1984 – 2009.

What will the reader gain: The reader will gain an up-to-date understanding of current treatment strategies for primary biliary cirrhosis using ursodeoxycholic acid and an appreciation of what conditions are improved with this therapy and what associated conditions are not.

Take-home message: Ursodeoxycholic acid in a dose of 13 – 15 mg/kg/day should be considered in all patients with primary biliary cirrhosis who have abnormal liver enzymes.     

熊去氧胆酸治疗早产儿胃肠外营养相关性胆汁淤积症的疗效及对患儿血清内毒素水平的影响

目的： 探讨熊去氧胆酸治疗早产儿胃肠外营养相关性胆汁淤积症的疗效及对患儿血清内毒素水平的影响。方法： 选自2013年1月—2015年12月期间我院收治的胃肠外营养相关性胆汁淤积症早产儿64例,依据随机数字表法随机分为观察组32例与对照组32例。对照组采取常规对症治疗,观察组在对照组基础上结合熊去氧胆酸胶囊。两组疗程均为2周。比较两组患儿肝功能指标水平变化,以及不良反应发生情况。结果： 两组血清TB、ALT、AST水平治疗前比较无统计学差异（P>0.05）;两组血清TB、ALT、AST水平治疗后明显降低（P<0.05）;观察组血清TB、ALT、AST水平治疗后低于对照组（P<0.05）;两组血清内毒素水平治疗前比较无统计学差异（P>0.05）;两组血清内毒素水平治疗后明显降低（P<0.05）;观察组血清内毒素水平治疗后低于对照组（P<0.05）;两组不良反应发生率比较无统计学差异（P>0.05）。结论： 熊去氧胆酸治疗早产儿胃肠外营养相关性胆汁淤积症的效果明显,可明显改善患儿肝功能,降低血清内毒素水平,具有重要临床研究价值。     

丙谷胺与熊去氧胆酸治疗胆囊结石疗效比较

目的：比较丙谷胺与熊去氧胆酸治疗胆囊结石的疗效。方法：将１６０例胆囊结石病人随机分为２组。丙谷胺组８０例（男性１２例，女性６８例；年龄３８±ｓ５ａ），用丙谷胺片每次５片（０．２ｇ／片），ｐｏｂｉｄ。熊去氧胆酸组８０例（男性１１例，女性６９例；年龄３７±６ａ），用熊去氧胆酸片４片（５０ｍｇ／片），ｐｏ，ｔｉｄ。２组病例均加用硝苯地平片每次１片（１０ｍｇ／片），ｐｏ，ｔｉｄ；３３％硫酸镁溶液２０ｍＬ，ｑｎ。２组疗程均为３ｍｏ。结果：丙谷胺组总有效率６０％，治愈率３０％，熊去氧胆酸组总有效率３９％和治愈率１２％（Ｐ＜０．０１）。结论：丙谷胺的疗效优于熊去氧胆酸。     

Transport mechanism of ursodeoxycholic acid in human placental BeWo cells

Ursodeoxycholic acid (UDCA) is a first‐line drug to treat intrahepatic cholestasis of pregnancy (ICP). However, its effects on the fetus are not clearly known. To better guide its clinical use, we aimed to study the mechanism underlying the placental transport of UDCA. The uptake and efflux of UDCA across placental apical membranes were studied using BeWo cells; effects of different exposure durations, UDCA concentrations, temperatures, and inhibitors of transporters were studied. A transwell assay was performed, and UDCA concentration in both fetal and maternal sides was measured using LC–MS/MS. Higher unidirectional transport of UDCA was observed in the basolateral‐to‐apical direction than in the apical‐to‐basolateral direction. Ko143 and verapamil, which are typical inhibitors of efflux transporters, significantly increased UDCA transport from different directions. UDCA uptake from the apical membrane of BeWo cells was time‐dependent, but sodium‐independent. It was inhibited by inhibitors of energy metabolism and of organic anion transporters, indicating an active transport mechanism. UDCA uptake from the apical membranes of BeWo cells could be mediated by organic anion‐transporting polypeptides, whereas its efflux could be mediated by breast cancer resistance protein and multidrug resistant protein 3. The results of the present study may provide a basis for UDCA use in pregnancy.     

熊去氧胆酸治疗婴儿巨细胞病毒肝炎的疗效观察

目的观察熊去氧胆酸治疗婴儿巨细胞病毒肝炎的疗效。方法所有病例均来自本院2005年1月至2008年4月收治的患者,共计54例。将上述54例病例随机分为治疗组29例与对照组25例。两组病例均给予更昔洛韦抗病毒,三磷腺苷(三磷酸腺苷)、辅酶A、肌苷、维生素C保肝,维持水、电解质、酸碱平衡等综合治疗。治疗组加用熊去氧胆酸10mg/kg.d,分3次服用。连续应用2周。结果治疗2周后,治疗组患儿在总胆红素、直接胆红素、间接胆红素、胆汁酸、谷丙转氨酶几项指标上与对照组有显著差异(P<0.05)。结论熊去氧胆酸能保护肝细胞,刺激肝胆分泌,促进黄疸消退,明显改善患儿受损的肝脏功能。     

熊去氧胆酸联合中药对胆囊结石家兔模型保胆取石术后胆汁酸 、胆固醇合成代谢的影响

目的 研究保胆取石术术后应用熊去氧胆酸联合中药对胆囊结石家兔模型术后胆汁酸、胆固醇合成代谢的影响.方法 选择雄性新西兰家兔60只为研究对象,建立胆囊结石模型后进行内镜下保胆取石术,根据术后处理方式不同分为3组,对照组给予普通饮食,模型组给予致石饮食,干预组给予致石饮食+熊去氧胆酸联合中药.检测3组家兔血清中胆固醇(TC)、总胆汁酸(TBA)、总胆红素(TBIL)含量以及胆固醇7-羟化酶(CYP7A1)和胆汁酸盐输出泵(BSEP)运输因子acbc11 mRNA含量.结果 干预后3周、5周时,模型组家兔血清中TC、TBIL含量高于对照组,TBA含量均低于对照组(t=3.571~24.374,P<0.05);干预组家兔血清中胆固醇TC、TBIL含量低于对照组,TBA含量均高于模型组(t=2.438~18.230,P<0.05);模型组家兔胆囊组织中CYP7A1和acbc11的mRNA含量低于对照组(t=11.369~20.096,P<0.05),干预组家兔胆囊组织中CYP7A1和acbc11的mRNA含量高于模型组(t=5.923~16.049,P<0.05).结论 熊去氧胆酸联合中药有助于修复受损胆固醇7-羟化酶和胆汁酸盐输出泵运输因子acbc11基因表达,调节胆汁酸、胆固醇、胆红素的代谢水平,预防保胆取石术后结石复发.     

Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid

To elucidate the effect of solidification processes on the redispersibility of drug nanocrystals (NC) during freeze-drying, ursodeoxycholic acid (UDCA) nanosuspensions were transformed into UDCA-NC via different solidification process included freezing and lyophilization. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of UDCA-NC was investigated, respectively. The results showed that the redispersibility of UDCA-NC was RDI_?20?°C?<?RDI_?80?°C?<?RDI_?196?°C during freezing, which indicated the redispersibility of UDCA-NC at the conventional temperature was better more than those at moderate and rigorous condition. Compared to the drying strengthen, the employed amount and type of stabilizers more dramatically affected the redispersibility of UDCA-NC during lyophilization. The hydroxypropylmethylcellulose and PVPK30 were effective to protect UDCA-NC from damage during lyophilization, which could homogeneously adsorb into the surface of NC to prevent from agglomerates. The sucrose and glucose achieved excellent performance that protected UDCA-NC from crystal growth during lyophilization, respectively. It was concluded that UDCA-NC was subjected to agglomeration during solidification transformation, and the degree of agglomeration suffered varied with the type and the amounts of stabilizers used, as well as different solidification conditions. The PVPK30-sucrose system was more effective to protect UDCA-NC from the damage during solidification process.