Total glycosides of Radix Gentianae are the active ingredients of some Chinese medicinal plants, such as Radix GentianaeMacrophyllae, Radix Gentianae and Swertiapatens. Gentiopicroside belongs to secoiridoid and is one of the main components in Gentianae total glycosides. It has some medical effects, for example, anti-inflammatory, analgesia, and benefit effects for liver, stomach and gallbladder. In clinical practice, Gentianaceae powder is used as a medicine with heat-clearing and damp-drying, clearing liver fire and improving liver functions. At present, its main dosage form is oral solid dosage forms. Because the partition coefficient of Gentiopicroside is relative low, it could not be well absorbed in-vivo with short half-life. The low oral bioavailability leads to low efficacy in clinical use. Therefore, the aim of this study is to develop gastric floating sustained-release solid dosage forms of Gentiopicroside. Study in this paper consist of the following parts: 1) Preparing of raw materials Gentian total glycosides, which includes the choice of crude herbs for extraction and purification; 2) Preparation and in-vitro evaluation of gastric floating sustained-release tablets and pellets of Gentian total glycosides. Specifically, it includes the formulation screening, establishing of the preparing technology and key technical parameters, as well as the study of in-vitro drug release. Results showed that based on the extraction yield and the medicinal materials price, GentianaMacrophylla is selected as the medicinal materials for extraction of Gentianae Total Glycosides. Both of bench-scale experiment and pilot-scale test have confirmed that the technology of water-alcohol hot extract and D-101 macroporous resin could be used to purify Gentianae Total Glycosides. Meanwhile, quality control standard of Gentianae Total Glycosides has been set up to control raw materials, which has relative constant composition and meet the purity requirements. In this paper, types of excipients were confirmed through screening on hydrophilic matrix material, swelling agent and aero-genesis materials. Then mixture design was utilized to optimize the formulation. Meanwhile, pharmaceutical performance of 12 types tablets including the tablet hardness, density, friability, swelling and erosion capacity, beginning floating time and drug release text, as well as the tablet residence time in volunteer stomach and animal blood concentration were investigated. The results also indicated that the extraction yield was satisfied. The optimized formulation of gastric floating sustained-release tablet could be retained in volunteers’ stomach for at least 6 hours. As a summary, this study has successfully set up the extraction and purification technology of Gentianae Total Glycosides from GentianaMacrophylla. The gastric residence time of GTG in absorption site were extended by preparation as gastric floating sustained-release tablets or pellets, which may enhance their oral bioavailability and clinical efficacy. This study has set a good example to the dosage form modernization of Chinese Medicine.

龍膽總苷是龍膽科植物秦艽、龍膽和獐牙菜等藥材的藥用活性成分。龍膽苦 苷（Gentiopicroside）為裂環烯醚萜類化合物，是龍膽總苷中的主要成分之一， 具有抗炎、鎮痛、保肝、健胃、利膽等作用，在臨床上主要以龍膽科植物藥材原 粉的形式入藥，在複方製劑中作為君藥使用，具有清熱燥濕、清瀉肝火和改善肝 功能等功效。製劑形式目前主要為普通固體口服製劑。因龍膽苦苷油水分配係數 小且半衰期短，所以口服後效果較差，生物利用度低。故為提高其生物利用度， 改善其臨床療效，本論文對將龍膽總苷製成胃內滯留漂浮型緩釋製劑，對龍膽總 苷的製備和胃漂浮微丸和胃漂浮片製劑成型進行了探索性研究。 本論文研究內容為：（1）龍膽總苷原料藥的製備，論文對原料藥製備藥材的 選擇、藥用活性成分龍膽總苷的提取、精製和中試工藝制進行了研究；（2）龍膽 總苷胃內滯留漂浮緩釋片的製備及其體外製劑學評價，論文對胃內滯留漂浮型緩 釋片的處方篩選、製劑工藝與關鍵技術參數的確定、小試樣品的體外釋藥曲線進 行了研究；（3）龍膽總苷胃漂浮緩釋微丸的研究及其體外製劑學評價，論文對胃 內滯留漂浮型緩釋微丸輔料處方，成型工藝及體外釋放特性等方面均進行了研 究。 研究方法和結果：本論文根據龍膽與秦艽藥材中龍膽總（苦）苷的提取率， 以及藥材價格等因素進行性價比綜合考慮，確定了以秦艽為龍膽總苷的提取用藥 材；經小試及中試實驗驗證，確定了以水-乙醇熱提工藝並經 D-101 大孔樹脂精 製的龍膽總苷製備工藝，同時制訂了龍膽總苷品質標準草案，為製劑的研究提供 了純度滿足要求且組成相對恒定的原料。本論文通過對凝膠骨架材料、膨脹劑和產氣物質的篩選等方式確定了龍膽 總苷胃漂浮片所用的輔料種類，採用混料設計方法對各輔料配比進行了優化，並 對 12 個處方的片劑進行了硬度、密度、脆碎度、溶脹溶蝕、起漂時間、釋放度 等體外製劑學性能考察，從而確定了成型工藝研究。 研究結果表明：以秦艽為提取用藥材，以水-醇熱提並經大孔樹脂精製的龍 膽總苷製備工藝產率可達 50%以上，且品質符合擬定標準要求。用優化確定的處 方工藝製備的胃內滯留漂浮型龍膽總苷緩釋片可以滿足其製劑學要求。 本論文的研究結果初步證明：將龍膽總苷製成胃內滯留漂浮型緩釋片，可以 大大延遲其在胃內的滯留時間，從而提高其在吸收部位的濃度，有望達到提高其 生物利用度，改善其臨床療效的目地。同時，本論文還將龍膽苦苷載於胃漂浮微 丸劑型，同樣可以達到定位緩釋的目的。 另外，本論文對於同類中藥藥物的製 劑改良和中藥製劑技術的發展都是一種有益的探索嘗試。