美他多辛的HPLC测定

采用HPLC法测定美他多辛的含量。色谱柱为Luna C18(2)柱，流动想为乙腈—0．2％磷酸(1：99)，检测波长205nm，平均回收率为99．8％，及RSD为0．77％。     

美他多辛栓剂的制备及含量测定

目的：探讨美他多辛栓剂的制备过程及其含量测定方法。方法：以美他多辛为主药制备栓剂,采用HPLC法测定栓剂中美他多辛的含量。色谱条件如下：Gemini 5U-C18色谱柱（250mm×4.6mm,5μm）;柱温：35℃;流动相：乙腈-0.1%磷酸溶液（1∶99）;流速：1ml/min;检测波长：205nm。结果：制备的美他多辛栓剂为米黄色圆锥形固体。美他多辛在20.2~101μg/ml浓度范围内呈良好线性关系,标准曲线方程为A=56.83 c＋47.88（r=0.999 9）。低、中、高3种浓度（40.4、60.6、80.8μg/ml）美他多辛的加样回收率分别为（99.97±0.032）%、（99.91±0.076）%和（99.86±0.046）%（n=3）。结论：本研究建立的栓剂制备方法可行,含量测定方法可用于美他多辛栓剂的研究。     

HPLC-ELSD测定美他多辛注射液有关物质

目的建立HPLC-ELSD测定美他多辛注射液有关物质的方法。方法色谱柱为Agilent Zorbax SB-C18柱(250 mm×4.6 mm,5μm),流动相为0.2 mol.L 1三氟乙酸溶液-甲醇(92∶8),流速为1.0 mL.min 1,检测器漂移管温度为55℃(低温型),载气压力为420 Pa。结果主要杂质与美他多辛有较好的分离度,所建立的方法可有效检测无紫外吸收的杂质。结论方法简单、可靠,适用于美他多辛的质量控制。     

Pharmacokinetics of metadoxine for injection after repeated doses in healthy volunteers

Alcohol-induced liver disease is one of the main epidemic problems nowadays. Metadoxine is a pyridoxine-pyrrolidone carboxylate with significant scavenging property. Metadoxine is able to accelerate the elimination of alcohol from the blood and tissues, help restore the functional structure of the liver and relieve neuro-psychological disorders associated with alcohol intoxication.1-3 The purpose of the study was to assay the pharmacokinetics of domestic metadoxine after repeated doses.     

美他多辛联合还原型谷胱甘肽治疗酒精性脂肪肝的临床观察

目的美他多辛联合还原型谷胱甘肽治疗酒精性脂肪肝的临床疗效,以及对肝功能异常和血脂代谢的影响。方法将80例酒精性肝病患者随机分为观察组和对照组各40例,对照组给予还原型谷胱甘肽,观察组在此基础上加用美他多辛,疗程3个月。结果观察组患者总有效率为95．00％,明显高于对照组的77．50％,二者差异有统计学意义（P〈0．05）。入组时,两组患者血清ALT、AST和GGT水平比较,差异无统计学意义（P〉0．05）;疗程结束后,两组患者血清ALT、AST和GGT水平较入院时下降（P〈0．05）,但是观察组患者下降幅度更明显（P〈0．05）。入组时,两组患者血清TC和TG水平比较,差异无统计学意义（P〉0．05）;疗程结束后,两组患者血清TC和TG水平较入院时下降（P〈0．05）,但是观察组患者下降幅度更明显（P〈0．05）。结论美他多辛联合还原型谷胱甘肽治疗酒精性脂肪肝具有较好的临床效果,显示改善患者的肝功能和调节血脂代谢功能,值得临床应用。     

美他多辛联合硫普罗宁治疗酒精性肝病的疗效观察

目的 观察美他多辛联合硫普罗宁治疗酒精性肝病的疗效.方法 60例酒精性肝病住院患者随机分为治疗组和对照组各30例,两组一般治疗相同,对照组用硫普罗宁,治疗组在对照组基础上加用美他多辛片.治疗前后分别查TBil、ALT、AST、GGT、A/G、TC、TG等生化指标,并记录临床症状和体征变化.结果 4周后,治疗组总有效率96.67％,明显高于对照组的76.67％；治疗组治疗后的TBil、ALT、AST、GGT、A/G、TC、TG水平明显低于对照组,差异均有统计学意义(P＜0.01).两组在治疗期间均无明显不良反应.结论 美他多辛和硫普罗宁联用疗效优于单用硫普罗宁.     

Fibrosis and glycogen stores depletion induced by prolonged biliary obstruction in the rat are ameliorated by metadoxine

Background/Aims: To evaluate liver‐beneficial properties of metadoxine, not related with alcohol metabolism, bioactivation of external toxins or antioxidant mechanisms, the chronic bile duct ligation (BDL) model was used and results were compared with colchicine. Methods: Seven groups (n=6) of male Wistar rats were used. Four groups were BDL and received metadoxine (60 mg/kg/12 h i.p.), colchicine (10 μg/rat/day/p.o.), both or vehicles; three groups were sham‐appropriate controls. Collagen content was determined by measuring hydroxyproline in liver samples; malondialdehyde (MDA) was used to estimate lipid peroxidation levels; glycogen was determined utilizing the anthrone reagent; gomory's trichromic stains of liver sections were performed. Results: Collagen increased four‐fold by BDL, metadoxine, colchicine or both prevented fibrosis partially; MDA levels increased three‐fold by BDL and no treatment had any significant effect; glycogen was almost depleted in the cirrhotic group, metadoxine preserved glycogen; bilirubins, and alanine aminotransferase and γ‐glutamyltranspeptidase activities increased several‐fold in the BDL group, and both drugs prevented these effects partially. The histopathological analysis correlated with biochemical data. Conclusions: Both compounds showed similar antifibrotic properties; metadoxine was more effective in preserving glycogen. Besides its antioxidant effects and its ability to induce alcohol metabolism, metadoxine possesses important antifibrotic and antinecrotic properties, and maintains energy stores efficiently.     

美他多辛联合多烯磷脂酰胆碱治疗酒精性肝病临床疗效观察

目的探讨美他多辛联合多烯磷脂酰胆碱治疗酒精性肝病的临床疗效。方法 60例酒精性肝病(ALD)患者随机分为治疗组和对照组,每组30例。对照组在一般治疗基础上给予多烯磷脂酰胆碱;治疗组在对照组基础上给予美他多辛;疗程均为4周。检测2组治疗前后血清谷丙转氨酶(ALT),谷草转氨酶(AST),胆红素(TBil),谷酰转肽酶(GGT)水平,比较2组治疗后症状、体征改善情况和临床有效率。结果 2组治疗后血清ALT、AST、TBil、GGT水平均明显降低。治疗组治疗后血清ALT、AST、TBil、GGT水平明显低于对照组。2组治疗后症状、体征改善情况无显著差异。治疗组临床有效率明显高于对照组。结论美他多辛和多烯磷脂酰胆碱联用治疗酒精性肝病,疗效优于单用多烯磷脂酰胆碱。     

单剂量美他多辛注射液在健康人体的药代动力学

目的研究美他多辛注射液在健康人体的药代动力学。方法10名健康受试者随机分为3组,先后静滴美他多辛600,900,1200mg,点滴时间为3h;2次实验间隔1周,用高效液相色谱法测定血药浓度。结果主要药代动力学参数Cmax分别为(4.4±0.79),(8.35±1.64)和(11.61±2.33)mg·L-1;t1/2分别为(0.78±0.09),(0.83±0.10)和(0.81±0.12)h;AUC0-tn分别为(12.02±2.074),(22.89±4.79)和(35.02±7.07)mg·h·L-1;AUC0-∞分别为(13.14±2.06),(23.52±4.6)和(35.46±7.48)mg·h·L-1。约有10%~30%的美他多辛以原形物经肾脏排泄。对3组t1/2分别做t检验,结果显示无显著性差异(P>0.05)。结论不同给药剂量,其分布及消除过程基本一致。     

美他多辛对大鼠的雄性生殖毒性

目的 :观察美他多辛对雄性大鼠的生殖毒性。 方法 :雄性SD大鼠每天经口给美他多辛0、500、1000、2000mg/kg,连续2周。分别于末次给药后24h和停药3周后各处死一半动物 ,检查睾丸和附睾等雄激素依赖组织的重量 ,计算脏/体比 ,并观察精子数量、活动度、存活率及精子形态。结果 :500mg/kg组无论给药后24h还是停药3周后观察 ,各项指标与对照组比较均无显著性差异。末次给药后24h观察 ,除了1000和2000mg/kg组包皮腺的脏/体比与对照组有轻度但有显著意义地降低(P<0.05)外 ,其余指标均无显著性差异。停药3周后观察 ,1000mg/kg组提肛肌/前列腺比、附睾/体重比降低 ,精子畸形率增高 ;而2000mg/kg组睾丸、附睾、包皮腺的脏/体比和提肛肌/前列腺比均下降 ,精子数量减少 ,存活率降低 ,活动度下降。结论 :雄性大鼠经口摄入美他多辛1000mg/kg以上 ,连续2周 ,对生殖系统有明显的毒性 ,且停药后能继续发展