体外仿生模型在微量元素形态分析及生物可给性和毒性评价中的应用
发布时间：2019-05-29 01:28
【摘要】：药物分析、食品分析常用实验动物模型,成本高,耗时,耗力。本文首次建立体外全仿生消化技术,依据化学仿生(人工胃、人工肠)与医学仿生(酶的作用)原理,将整体药物研究(仿生消化食糜更接近药物在胃肠消化道内达到平衡后的有效成分群)与分子药物研究法(以微量元素为指标)相结合,模拟中药经胃肠环境的转运机制,综合胃肠消化酶、胃肠酸度、体温、节律性蠕动、消化时间等要素,应用于样品前处理,方法合乎中医药理论的系统观、整体观。 鉴于消化管和血管间的生物膜是类脂质膜,首次以单层脂质体为细胞膜模型考察中药仿生消化食糜在单层脂质体-水体系中的分配行为。基于吸收性差异,首次以单层脂质体亲合态、水溶态界定食糜中微量元素形态;以单层脂质体亲合态含量评价微量元素的生物可给性,探讨胃肠消化机制,制订推荐剂量和限制剂量,进行安全性和危险性评价。具体情况如下: (1)分别应用“单层脂质体萃取技术”和“大鼠胃在体吸收、肠单向灌流”模型,验证体外全仿生消化-单层脂质体萃取技术合理性。中药(金线莲和黄芪)水煎液胃、肠仿生消化食糜中微量元素大鼠在体胃、肠吸收量(GAMs)和胃肠单层脂质体亲和态量(MLSMs)比较结果表明:GAMs和MLSMs均和食糜中微量金属总量成正比,说明微量金属配合物在胃肠中主要以被动运输方式吸收;GAMs与MLSMs两者比值出现频率在0.8～1.2范围内最高,接近70%,在0.8～1.4范围内约84%,不计入低频率点时,比值呈正态分布。因此,本项目采用的胃肠细胞膜模型基本合理,特别适合于被动吸收模式,可望替代动物实验研究,用于药物分析及毒理测试。 (2)海带中微量金属的形态和生物可给性与总量密切相关,受到胃肠消化道的酸度、无机和有机物成分影响,其中消化酶影响显著。海带安全日摄入剂量和最大日摄入剂量,成年人分别为33.3 g/day和230.8 g/day。 (3)川乌和白芍配伍研究表明:川乌(A)和白芍(B)最佳配伍比例为1A:1B;按1A:1B配伍,成年女性或男性的安全剂量分别应少于295.0 g/day和214.5 g/day,最高剂量不超过1072.7 g/day。 (4)连花清瘟胶囊中微量金属含量丰富,主要在肠被吸收;重金属As、Cd和Pb的总量分别为0.38、0.07和1.60 mg/kg,远小于《药用植物及制剂进出口绿色行业标准》中规定重金属总量。
[Abstract]:Drug analysis, food analysis commonly used experimental animal models, high cost, time-consuming, power consumption. In this paper, the whole bionic digestion technique in vitro was established for the first time. According to the principle of chemical biomimetic (artificial stomach, artificial intestine) and medical biomimetic (the action of enzyme), To simulate the transport mechanism of traditional Chinese medicine through gastrointestinal environment, the whole drug research (bionic digesting chyme is closer to the balanced active component group of drugs in gastrointestinal tract) and the molecular drug research method (taking trace elements as the index) are combined to simulate the transport mechanism of traditional Chinese medicine through gastrointestinal environment. Comprehensive gastrointestinal digestive enzymes, gastrointestinal acidity, body temperature, rhythmic peristalsis, digestion time and other elements, applied to sample pretreatment, the method is in line with the systematic view of traditional Chinese medicine theory, the overall view. In view of the fact that the biofilm between digestive tube and blood vessel is lipid-like membrane, the distribution behavior of biomimetic digested chyme in monolayer liposomes-water system was investigated for the first time by using monolayer liposomes as cell membrane model. Based on the difference of absorption, the morphology of trace elements in chyme was defined by monolayer liposomes affinity and water-soluble state for the first time. The bioavailability of trace elements was evaluated by the affinity content of monolayer liposomes, the mechanism of gastrointestinal digestion was discussed, the recommended dose and limited dose were worked out, and the safety and risk assessment were carried out. The specific situation is as follows: (1) the "monolayer liposome extraction technique" and "rat gastric absorption in vivo, intestinal one-way perfusion" model were used to verify the rationality of in vitro bionic digestion-monolayer liposomes extraction technology. Traditional Chinese medicine (Acanthopanax senticosus and Astragalus membranaceus) decoction stomach, intestinal bionic digestion of trace elements in chyme in the stomach of rats, The results of intestinal absorption (GAMs) and gastrointestinal monolayer liposomes affinity (MLSMs) showed that GAMs and MLSMs were proportional to the total amount of trace metals in chyme, indicating that trace metal complexes were mainly absorbed by passive transport in gastrointestinal tract. The frequency of the ratio of GAMs to MLSMs is the highest in the range of 0.8 鈮，
本文编号：2487529
[Abstract]:Drug analysis, food analysis commonly used experimental animal models, high cost, time-consuming, power consumption. In this paper, the whole bionic digestion technique in vitro was established for the first time. According to the principle of chemical biomimetic (artificial stomach, artificial intestine) and medical biomimetic (the action of enzyme), To simulate the transport mechanism of traditional Chinese medicine through gastrointestinal environment, the whole drug research (bionic digesting chyme is closer to the balanced active component group of drugs in gastrointestinal tract) and the molecular drug research method (taking trace elements as the index) are combined to simulate the transport mechanism of traditional Chinese medicine through gastrointestinal environment. Comprehensive gastrointestinal digestive enzymes, gastrointestinal acidity, body temperature, rhythmic peristalsis, digestion time and other elements, applied to sample pretreatment, the method is in line with the systematic view of traditional Chinese medicine theory, the overall view. In view of the fact that the biofilm between digestive tube and blood vessel is lipid-like membrane, the distribution behavior of biomimetic digested chyme in monolayer liposomes-water system was investigated for the first time by using monolayer liposomes as cell membrane model. Based on the difference of absorption, the morphology of trace elements in chyme was defined by monolayer liposomes affinity and water-soluble state for the first time. The bioavailability of trace elements was evaluated by the affinity content of monolayer liposomes, the mechanism of gastrointestinal digestion was discussed, the recommended dose and limited dose were worked out, and the safety and risk assessment were carried out. The specific situation is as follows: (1) the "monolayer liposome extraction technique" and "rat gastric absorption in vivo, intestinal one-way perfusion" model were used to verify the rationality of in vitro bionic digestion-monolayer liposomes extraction technology. Traditional Chinese medicine (Acanthopanax senticosus and Astragalus membranaceus) decoction stomach, intestinal bionic digestion of trace elements in chyme in the stomach of rats, The results of intestinal absorption (GAMs) and gastrointestinal monolayer liposomes affinity (MLSMs) showed that GAMs and MLSMs were proportional to the total amount of trace metals in chyme, indicating that trace metal complexes were mainly absorbed by passive transport in gastrointestinal tract. The frequency of the ratio of GAMs to MLSMs is the highest in the range of 0.8 鈮，
本文编号：2487529
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