芍藥甘草湯中自組裝納米粒形成對(duì)甘草主要成分體外釋放和腸吸收的影響

沈成英 李小芳 朱君君 申寶德 袁海龍 胡建新

中圖分類號(hào) R283 文獻(xiàn)標(biāo)志碼 A 文章編號(hào) 1001-0408（2022）03-0338-06

DOI 10.6039/j.issn.1001-0408.2022.03.14

摘 要 目的 研究芍藥甘草湯中自組裝納米粒（SGD-SAN）形成對(duì)甘草主要成分體外釋放和腸吸收的影響。方法 制備甘草單煎液（GSD）、芍藥單煎液（SSD）、芍藥-甘草單煎混合液（MSSGD）和SGD（即芍藥、甘草合煎液），并對(duì)其中的SAN進(jìn)行表征。采用高效液相色譜法測(cè)定甘草中7種主要成分（芹糖甘草苷、甘草苷、芹糖異甘草苷、異甘草苷、甘草素、甘草酸、異甘草素）的含量。采用透析袋法，以pH1.2 HCl溶液和pH6.8磷酸鹽緩沖液（PBS）為釋放介質(zhì)，考察SGD-SAN形成對(duì)甘草中7種主要成分體外釋放的影響;采用在體單向腸灌流實(shí)驗(yàn)考察SGD-SAN形成對(duì)甘草中7種主要成分在大鼠腸段吸收的影響。結(jié)果 GSD、MSSGD和SGD中存在粒徑為200～300 nm、多分散性指數(shù)為0.3～0.5的SAN;透射電鏡觀察結(jié)果顯示，GSD-SAN、MSSGD-SAN呈棒狀，SGD-SAN呈不規(guī)則球形。體外釋放實(shí)驗(yàn)結(jié)果顯示，在pH1.2 HCl溶液中，SGD-SAN形成能顯著增加甘草素、異甘草素和甘草酸的體外釋放，對(duì)其他成分的釋放無(wú)明顯影響;在pH6.8 PBS中，SGD-SAN形成對(duì)甘草中各成分的釋放均沒(méi)有明顯影響。在體單向腸灌流實(shí)驗(yàn)結(jié)果顯示，SGD-SAN形成能顯著促進(jìn)甘草中各成分在回腸的吸收。結(jié)論 SGD-SAN形成能顯著改善甘草中難溶性成分的體外釋放、促進(jìn)甘草中主要成分的腸吸收，是芍藥、甘草配伍增效的物理結(jié)構(gòu)基礎(chǔ)。

關(guān)鍵詞 自組裝納米粒;芍藥甘草湯;甘草;難溶性成分;體外釋放;腸吸收

Effects of self-assembled nanoparticles from Shaoyao gancao decoction on the in vitro release and intestinal absorption of the main components of Glycyrrhiza uralensis

SHEN Chengying1，2，LI Xiaofang2，ZHU Junjun3，SHEN Baode4，YUAN Hailong3，HU Jianxin1（1. Dept. of Pharmacy， Jiangxi Provincial Peoples Hospital， Nanchang 330006， China; 2. School of Pharmacy， Chengdu University of Traditional Chinese Medicine， Chengdu 611137， China; 3. Dept. of Pharmacy， Air Force Medical Center， the Chinese Peoples Liberation Army， Beijing 100142， China; 4. Key Lab of Modern Traditional Chinese Medicine Preparation of the Ministry of Education， Jiangxi University of Chinese Medicine， Nanchang 330004， China）

ABSTRACT? ?OBJECTIVE To study the effects of self-assembled nanoparticles from Shaoyao gancao decoction （SGD-SAN） on the in vitro release and intestinal absorption of the main components of Glycyrrhiza uralensis. METHODS Gancao single decoction （GSD）， Shaoyao single decoction （SSD）， mixed suspension of Shaoyao and Gancao single decoction （MSSGD） and SGD （i.e. Shaoyao-Gancao decoction） were prepared， and SAN was characterized. HPLC method was adopted to determine the contents of 7 main components （liquiritin apioside， liquiritin， isoliquiritin apioside， isoliquiritin， liquiritigenin， glycyrrhizic acid， isoliquiritigenin） in G. uralensis. The dialysis bag method was used to investigate the effects of the formation of SGD-SAN on in vitro release of 7 main components in G. uralensis with pH1.2 HCl solution and pH6.8 phosphate buffered solution （PBS） as release media. Single-pass intestinal perfusion study was performed to investigate the effects of the formation of SGD-SAN on the intestinal absorption of 7 main components from G. uralensis. RESULTS SAN with particle size of 200-300 nm and polydispersity index of 0.3-0.5 was found in GSD， MSSGD and SGD. GSD-SAN and MSSGD-SAN were in rod shape while SGD-SAN was irregularly spherical under transmission electron microscope. The results of in vitro release study showed that the formation of SGD-SAN could significantly increase in vitro release of liquiritigenin， isoliquiritigenin and glycyrrhizic acid， and had no effect on other components of G. uralensis in pH1.2 HCl solution. The formation of SGD-SAN also had no effect on the release of each component from G. uralensis in pH6.8 PBS. The results of intestinal perfusion experiments showed that the formation of SGD-SAN could significantly promote the absorption of each component from G. uralensis in the ileum. CONCLUSIONS The formation of SGD-SAN significantly improves the in vitro release of poorly soluble components from G. uralensis and promotes the intestinal absorption of main components from G. uralensis， which is the physical structure basis for the compatibility and synergy of Paeonia lactiflora and G. uralensis.