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目的:通过模拟人体胃肠环境,比较不同溶出介质中熟大黄鞣质及蒽醌类成分的溶出量差异,从体外溶出的角度探讨影响中药量-效关系的可能因素。方法:取同一批生大黄炮制成熟大黄,选取4种不同溶出介质,采用浆法进行熟大黄体外溶出试验,以UPLC法测定大黄直接溶出和水解后鞣质及蒽醌类成分的含量,色谱柱为Waters Acquity BEHC18柱(50mm×2.1mm,1.7μm),流动相为0.1%磷酸-水(A)-甲醇(B)线性梯度洗脱:0-1.5min,100%A;1.5-2.0min,100%-95%A;2.0-3.5min,95%-86%A;3.5-5.0min,86%-72%A;5.0-8.0min,72%-64%A;8.0-10.0min,64%-52%A;10.0-13.0min,52%-30%A;13-16.0min,30%-16%A。检测波长254nm,流速0.75mL/min,柱温35℃。结果:①生大黄炮制成熟大黄后,已检测不到儿茶素和表儿茶素。②鞣质和蒽醌类成分分别在30、60min后基本达到最大溶出。③水解前后均能检测到没食子酸,且水解后测得含量增加。④水解前仅大黄酸在人工肠液和磷酸盐缓冲液中能检测到,且其在磷酸盐缓冲液中的溶出量大于在人工肠液中的溶出量。⑤同一蒽醌衍生物在人工胃液中含量变化较慢,在水、人工肠液和磷酸盐缓冲液中含量变化相对较快,同时,比较1h内的5种蒽醌含量变化可知,大黄素甲醚在各介质中变化最慢,含量最低,其次是大黄素。结论:不同溶出介质对鞣质和蒽醌类成分的溶出量有重要影响,没食子酸的溶出量大于蒽醌类成分(结合蒽醌),蒽醌类成分在人工肠液和磷酸盐缓冲液中溶出较快,说明小肠和大肠可能是蒽醌溶出的主要部位。
OBJECTIVE: To explore the possible factors that affect the dose-response relationship of Chinese herbs by simulating the human gastrointestinal environment and comparing the dissolution rates of the constituents of ripe rhubarb and anthraquinones in different dissolution media. Methods: Rhubarb was made from the same batch of rhubarb, and four kinds of dissolution mediums were selected. The in vitro dissolution test of Rhubarb was carried out by using the plasma method. The content of tannin and anthraquinones in Rhubarb after direct dissolution and hydrolysis was determined by UPLC. Was eluted with a linear gradient of 0.1% phosphoric acid-water (A) -methanol (B) on a Waters Acquity BEHC18 column (50mm × 2.1mm, 1.7μm) with a mobile phase of 0-1.5min, 100% A; 1.5-2.0min, 100% -95% A; 2.0-3.5 min, 95% -86% A; 3.5-5.0 min, 86% -72% A; 5.0-8.0 min, 72% -64% -52% A; 10.0-13.0 min, 52% -30% A; 13-16.0 min, 30% -16% A. Detection wavelength 254nm, flow rate 0.75mL / min, column temperature 35 ℃. Results: ① Rhubarb rhubarb cooked mature, has been undetectable catechin and epicatechin. ② The tannins and anthraquinones basically reached the maximum dissolution after 30 and 60 minutes, respectively. ③ before and after hydrolysis can detect gallic acid, and measured after hydrolysis increased content. (4) Only rhein can be detected in artificial intestinal juice and phosphate buffer before hydrolysis, and its dissolution rate in phosphate buffer solution is greater than that in artificial intestinal juice. ⑤ The same anthraquinone derivatives changed slowly in the artificial gastric juice, and their contents in water, artificial intestinal juice and phosphate buffer changed relatively fast. Meanwhile, compared with the content of 5 anthraquinones in 1h, The slowest change in the medium, the lowest content, followed by emodin. CONCLUSION: Different dissolution media have significant influence on the dissolution of tannin and anthraquinone, the dissolution of gallic acid is greater than that of anthraquinone (anthraquinone), anthraquinone is dissolved in artificial intestinal juice and phosphate buffer Faster, indicating that the small intestine and the large intestine may be the main part of anthraquinone dissolution.