摘要
目的通过模拟人体胃肠消化液条件,比较不同溶出介质中动物结石药物牛黄及其代用品人工牛黄中胆汁酸类成分的溶出量差异,从体外溶出的角度探讨影响难溶中药疗效的可能因素。方法分别取同一批天然牛黄、人工牛黄,分别加入3种不同溶出介质(人工胃液、小肠液、大肠液),平行提取处理,以UPLC法测定胆汁酸类成分的溶出量,以甲醇中的溶出量为参比,计算各胆汁酸成分的相对溶出率。液相检测色谱柱为WatersAcquityCSH柱(50mm×2.1mm,1.7μm),流动相为乙腈(A)-0.2%甲酸-水(B),线性梯度洗脱:0～2分钟,10%A;2～3分钟,12%～25%A;3～3.01分钟,25%～35%A;3.01～10分钟,35%～37%A;10～17分钟,37%～43%A;17～17.01分钟,43%～48%A;17.01～20分钟,48%～52%A。检测波长254nm,流速0.4ml/min,柱温35℃。结果牛黄中胆汁酸类成分在人工大肠液(pH7.6)中溶出率高于人工胃液和小肠液;天然牛黄中,除去氧胆酸外,各胆汁酸成分的溶出率均高于人工牛黄,其中鹅去氧胆酸相差9.13倍;天然牛黄中甘氨胆酸、甘氨去氧胆酸和鹅去氧胆酸溶出率较高,而现行药典质量控制指标胆酸的溶出较差。结论以胆汁酸类成分来看,天然牛黄溶出能力高于人工牛黄,可能是人工牛黄临床疗效低于天然牛黄的原因之一。加强难溶性中药的溶出研究,对提高相关制剂的疗效、节约药材等具有重要意义。
Objective In this paper, the potential influencing factors that can affect the curative effect of poorly soluble Chinese medicines, e.g. the animal drug calculus boris（ Calculus bovis and artificial Calculus boris）, are investigated through simulating human different digestive media to find the diversities of the dissolution of bile acids in calculus bovis. Methods Calculus bovis and artificial Calculus bovis were added into three kinds of artificial digestive media （gastric, large intestine and small intestine media） and the dissolution amounts of bile acids were determined by ultra performance liquid chromatography. The relative dissolution rates of bile acids in artificial digestive media were calculated referring to the dissolution amount in methanol. The compounds were separated on a Water Acquity CSH UPLC column （50 mm x 2.1 ram, 1.7 tLm） with a linear gradient eIution of acetonitrile （A） -0.2% formic acid in water and methanol（v/v, B）. The gradient elution procedure were： 0 - 2 min, 10% A;2-3 min, 12%-25% A;3 - 3.01 min,25%-35% A;3.01-10 min,35%-37% A; 10-17 min,37%-43% A; 17-17.01 min,43% - 48% A ; 17.01-20 min,48%-52% A. The flow rate was kept at 0.40 ml/min and the detector was set at 254 nm. The column temperature was maintained at 35~C. Results The dissolution rates of Calculus boris bile acids in artificial large intestine media （pH7.6） was higher than that in artificial gastric media and artificial small intestine media. The dissolution rates of bile acids in natural Calculus boris was higher than that in artificial Calculus bovis with the exception of deoxycholic acid. Chenodeoxycholic acid in natural Calculus bovis was 9.13 times higher than that in artificial Calculus boris. The dissolution rates of glycocholic acid, glycodeoxycholic acid and chenodeoxycholic acid were high in the natural Calculus boris, but cholic acid, the quality control marker compound in the Chinese Pharmacopoeia dissolved less than others. Conclusions In terms of the dissolution of bile acids, natural Calculus bovis dissolved better than artificial Calculus boris, which might be considered as one of the reasons that the clinical curative effect of natural Calculus boris is better than artificial one. It is important to emphasize on the dissolution research of poorly soluble Chinese Medicines for improving their efficacies and saving the raw materials.
出处
《环球中医药》
CAS
2012年第3期165-169,共5页
Global Traditional Chinese Medicine
基金
科技部公益性行业专项(200807020)
国家自然科学基金(30973947)
军队后勤科研项目(司科2010-89)
关键词
牛黄
胆汁酸
溶出
人工消化液
高效液相色谱
Calculus bovis
Bile acid
Dissolution
Artificial digestive media
Ultra performance liquid chromatography
