目的 比较砂生槐子总生物碱水剂和片剂的体内外性质。方法 将砂生槐子制备成总生物碱浸膏，再用生理盐水稀释成水剂；通过体外黏附力考察筛选出生物黏附材料海藻酸钠、卡波姆的最佳比例，制备砂生槐子总生物碱生物黏附片。采用体外pH转换两步（pH值分别为1.4、6.5）溶出实验评价砂生槐子总生物碱水剂和片剂在胃肠道中的扩散行为。将20只SD大鼠随机分为2组，每组10只，分别ig给予砂生槐子总生物碱片剂和水剂，给药剂量均为7 mg·kg⁻¹，于给药后0.25、0.50、1.00、2.00、3.00、4.00、5.00、6.00、8.00、10.00、12.00、24.00、36.00、48.00 h取血200～400 μL于EDTA-Na₂制备好的离心管中，分离血浆，超高效液相色谱（UHPLC）法检测苦参碱、氧化苦参碱、槐定碱的质量浓度。结果 海藻酸钠与卡波姆的比例为2∶1时，离体肠组织的黏附力最大，为（563.43±20.38）N。体外pH转换溶出实验显示水剂进入模拟胃液后迅速扩散；片剂在模拟胃液（pH＝1.4）中几乎不溶解，模拟肠液（pH＝6.5）中迅速溶解释放，1 h的累积溶出率在75%以上。药动学实验表明，水剂组的苦参碱、氧化苦参碱、槐定碱的峰浓度（C_max）分别是片剂组的2.2、1.9、2.4倍；水剂组各生物碱的达峰时间（t_max）均显著小于片剂组（P＜0.05）；水剂组氧化苦参碱的血药浓度-时间曲线下面积AUC_0-∞是片剂组的2.5倍、槐定碱的AUC_0-∞是片剂组的3.5倍。结论 砂生槐子生物碱水剂体外迅速扩散，体内生物利用度优于片剂。

Objective The purpose of this study was to compare the in vivo and in vitro properties of different formulations of the total alkaloids of Sophora moocrorftiana. Method Sophora moocrorftiana seeds was prepared into an extract, which is then diluted with physiological saline to form an aqueous solution. The best ratio of bioadhesive materials was screened out through in vitro adhesion investigation, and the total alkaloid bioadhesive tablets of Sophora moocrorftiana were prepared. The in vitro pH conversion dissolution test was used to evaluate the diffusion behavior of different preparations in the gastrointestinal tract. Twenty SD rats were randomly divided into two groups with ten rats in each group. They were given total alkaloid tablets and water intragaigally at the dose of 7.0 mg·kg⁻¹, respectively. At 0.25, 0.50, 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00 h after administration, blood was collected from 200 to 400 μL in a centrifuge tube prepared by EDTA-Na₂ for plasma separation. The mass concentrations of matrine, oxymatrine and sophoridine were determined by UHPLC. Result When the ratio of the adhesive material sodium alginate to carbomer was 2 : 1, the adhesion force of the isolated intestinal tissue was the largest, which was (563.43 ± 20.38) N. The in vitro pH conversion dissolution test showed that the aqueous solution diffused rapidly after entering the simulated gastric juice; the tablet was almost insoluble in the simulated gastric juice (pH = 1.4), and the drug was quickly dissolved and released in the simulated intestinal juice (pH = 6.5). The cumulative dissolution rate of 1h was 75% above. In vivo oral bioavailability experiments showed that the peak concentrations of matrine, oxymatrine, and sophoridine in the liquid group were 2.2, 1.9, and 2.4 times that of the tablet group, respectively. The peak time T_max of each alkaloid in the liquid group was less than that of the tablet group (P < 0.05). The AUC_(0-∞) of oxymatrine of the total alkaloids of Sophora moocrorftiana was 2.5 times that of the tablet group, and the AUC_(0-∞) of sophoridine of the water group was 3.5 times that of the tablet group. Conclusion Sophora moocrorftiana alkaloids in water spread rapidly in vitro, and the bioavailability in vivo was better than that of tablets.

R944

国家自然科学基金资助项目（81960641）；青海大学青年基金项目团队资助（2020-QYY-1）