【摘要】：藥物分析、食品分析常用實驗動物模型,成本高,耗時,耗力。本文首次建立體外全仿生消化技術,依據(jù)化學仿生(人工胃、人工腸)與醫(yī)學仿生(酶的作用)原理,將整體藥物研究(仿生消化食糜更接近藥物在胃腸消化道內(nèi)達到平衡后的有效成分群)與分子藥物研究法(以微量元素為指標)相結合,模擬中藥經(jīng)胃腸環(huán)境的轉運機制,綜合胃腸消化酶、胃腸酸度、體溫、節(jié)律性蠕動、消化時間等要素,應用于樣品前處理,方法合乎中醫(yī)藥理論的系統(tǒng)觀、整體觀。 鑒于消化管和血管間的生物膜是類脂質膜,首次以單層脂質體為細胞膜模型考察中藥仿生消化食糜在單層脂質體-水體系中的分配行為�；谖招圆町�,首次以單層脂質體親合態(tài)、水溶態(tài)界定食糜中微量元素形態(tài);以單層脂質體親合態(tài)含量評價微量元素的生物可給性,探討胃腸消化機制,制訂推薦劑量和限制劑量,進行安全性和危險性評價。具體情況如下: (1)分別應用“單層脂質體萃取技術”和“大鼠胃在體吸收、腸單向灌流”模型,驗證體外全仿生消化-單層脂質體萃取技術合理性。中藥(金線蓮和黃芪)水煎液胃、腸仿生消化食糜中微量元素大鼠在體胃、腸吸收量(GAMs)和胃腸單層脂質體親和態(tài)量(MLSMs)比較結果表明:GAMs和MLSMs均和食糜中微量金屬總量成正比,說明微量金屬配合物在胃腸中主要以被動運輸方式吸收;GAMs與MLSMs兩者比值出現(xiàn)頻率在0.8～1.2范圍內(nèi)最高,接近70%,在0.8～1.4范圍內(nèi)約84%,不計入低頻率點時,比值呈正態(tài)分布。因此,本項目采用的胃腸細胞膜模型基本合理,特別適合于被動吸收模式,可望替代動物實驗研究,用于藥物分析及毒理測試。 (2)海帶中微量金屬的形態(tài)和生物可給性與總量密切相關,受到胃腸消化道的酸度、無機和有機物成分影響,其中消化酶影響顯著。海帶安全日攝入劑量和最大日攝入劑量,成年人分別為33.3 g/day和230.8 g/day。 (3)川烏和白芍配伍研究表明:川烏(A)和白芍(B)最佳配伍比例為1A:1B;按1A:1B配伍,成年女性或男性的安全劑量分別應少于295.0 g/day和214.5 g/day,最高劑量不超過1072.7 g/day。 (4)連花清瘟膠囊中微量金屬含量豐富,主要在腸被吸收;重金屬As、Cd和Pb的總量分別為0.38、0.07和1.60 mg/kg,遠小于《藥用植物及制劑進出口綠色行業(yè)標準》中規(guī)定重金屬總量。
[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，

本文編號：2487529