江伯源 國立中興大學

「中醫藥」在人類醫療史上已超過千年，近年更逐漸在全世界各大醫學研究中心及醫藥市場風行，全球相關中草藥產值近1000億美元，每年以10%速率快速成長，其中「科學濃縮中藥」更是市場之主流產品。「台灣」是全世界「科學中藥」之發源地之一，「粉」、「粒」、「液」、「膠囊」等劑型是市場主要銷售型態，由於國內中醫師用藥習慣及全民健保中醫藥給藥型式，以「科學濃縮—粉、粒」為主，在製藥技術及品質、安全性享譽國際，近年在中醫藥委員會及廠商共同努力下，正努力推動成為全球之「中草藥科技島」。台灣目前中藥材料大都以進口為主，大陸是全世界最大中藥材生產地；由於全球中藥材需求量大增、對岸之經濟快速成長，以致中藥材之成本大增；加上國內「科學中藥」之供藥、給藥、服藥量是根據中華藥典—藥方規定之基本製程，「有效成分」及「劑量」更是品質管制重點，以致製造成本增加，造成各藥廠之經營壓力及市場競爭力日減。「提高有效成分萃取」、「濃縮、包覆率提升」、「造粒成功率、品質安定」是國內GMP中藥廠一直努力的目標，藉製備技術提升、有效管理得以增加市場競爭力，但效果日益減少，如何開創台灣中醫藥產業新發展方向、增加競爭力式產、官、學、研當前重要之使命及待突破之瓶頸。 ◎本年度計畫—“以高黏度浸膏系統探討中(草)藥造粒新製程及抗結塊技術研發”，擬以”枸杞及地黃(或麥冬)萃取、濃縮—高黏度浸膏”為藥材，模擬中草藥高黏度藥材造粒機制，建立控制因子評估、新造粒核心技術、抗結塊技術研發及其品質修飾評估，希盼能建立高黏度浸膏造粒技術、提升包覆率、粒子成型性及品質安定性，協助中藥產業增加技術及新藥材產品競爭力、提升中醫藥產業之創新。本實驗分為下列各項主題進行：(一)枸杞及地黃(或麥冬)多醣及機能成分分析：(1)探討枸杞及地黃(或麥冬)多醣分離、單醣成分分析 (2)機能成分分析：總多酚化合物、總類黃酮、總類胡蘿蔔素、β-carotene (3)抗氧化活性：清除DPPH自由基能力、TEAC、螯合鐵離子能力、?自由基清除能力、清除超氧陰離子能力；(二)枸杞及地黃(或麥冬)多醣物性及成膜性分析：A.浸膏溶離分析：(1)動態流變性、黏度分析、連續黏度(熱、冷狀態黏度變化及安定性) (2)物性分析：界面張力、接觸角度、穿透時間、導電度、固有黏度。B.浸膏成膜特性：(1)膜沾黏性 (2)玻璃轉換溫度(Tg)；(三)高黏度浸膏模式系統評估：(1)濃度 (2)溫度 (3)pH (4)金屬離子系統對黏度及造粒評估；(四)賦型劑操作參數評估：(1)澱粉 (2)浸膏 (3)澱粉+浸膏：(a)理化性質 (b)成膜性 (c)吸濕特性；(五)新型造粒技術評估與修飾：A.造粒操作參數：(1)平面噴霧流量 (2)理論液滴穿透時間 (3)入料流速 (4)熱風溫度 B.微粒子品質修飾評估：粒徑、色澤、外型(SEM)、水分、水活性、X-Ray、示差熱掃描分析(DSC)、玻璃轉換溫度、粒子膨潤力與溶解度、多醣包覆率等；(六)抗結塊技術研發與改善：A.粒子結塊機制及影響因子探討：結塊機制模組建立、玻璃轉換溫度、水分含量、水活性、表面能量、粉體流變、吸濕曲線、粒徑、型態分析及粒徑成長速率評估、載藥率變化分析。B.賦型劑配方及操作參數修飾：澱粉、膠、maltodextrin、溫度、濕度參數。C.抗結塊技術評估、改善：藥廠配合評估、現場模擬分析、測試。

關鍵字：中草藥、流動床造粒、抗結塊、枸杞及地黃(或麥冬)、黏度

Stugy on Development of New Granulation of Chinese Herbal Medicine and Anti-caking Technology by Extract System with High Viscosity

Po-Yuan Chiang National Chung Hsing University

Chinese herbal medicine has been used for thousands of years in the history of human medicine. In recent years, Chinese herbal medicine has received importance from medical research centers and large pharmaceuticals all over the world. The value of Chinese herbal medicine is about hundred billions with a growth rate of 10% every year. The "concentrated herbal extract" is the mainstream product in the global market. Taiwan is one of the places of origin of Chinese herbal medicine. The normal form of drug in the market includes powder, particle, solution and capsule. Powder and particle are the mainstream form of concentrated herbal extracts because of the domestic custom. Taiwan is famous all over the world for her pharmacy technology, quality and safety. Recently, the Committee on Chinese Medicine and Pharmacy and factories advance in as the "Chinese herb-medicine technology island ". In Taiwan, most of the Chinese herbal medicine is imported and China is the largest place of production. The cost increased because the requirement increased and the economic advanced rapidly in China. "Raising the ratio of extraction", " raising the ratio of concentration and loading efficiency” and "raising the strike-rate and stability of quality " are the targets of GMP Chinese herbal medicine factory. But the efficiency is decreasing with the increase of new technology and management. New development and increasing competitiveness are important for related industries, government departments, academia and researches. The research plan, " Study on the Development of New Granulation of Chinese Herbal Medicine and Anti-caking Technology by Extract System with High Viscosity ", uses Goji and extracts of Goji with high viscosity as the materials. Goji is the representative material of the high viscosity extraction system. Extraction of Goji uses fluid bed granulation to establish the mechanism, operational parameters and development of new granulation technology, anti-caking technology and improvement of the quality. It enhances the competitiveness of technology, products made by new materials and creativity in the Chinese herbal product. This study is carried out based on six topics, (1) analysis of polysaccharide and functional ingredients of Goji, (2) analysis of physical property and membrane formability of Goji polysaccharide, (3) estimation of high viscosity extraction system, (4) estimation of operational parameters of binders, (5) estimation and modification of new granulation technology and (6) development and improvement of anti-caking technology. (1) Analysis of polysaccharide and functional ingredients of Goji：Goji was used as the material in this study. The study separates the polysaccharide and analyses thecomposition of monosaccharide. This study also examines the content of functional ingredients of Goji including total phenol, flavonoids and total carotene. The antioxidant activity includes DPPH, (2) Analysis of physical property and membrane formability of Goji polysaccharide：This study is separated into two parts, (I) analysis of solution of Goji extracts and (II) analysis of membrane formed by Goji extracts. (I) Analysis of solution of Goji extracts includes rheology, physical property, contact angle, penetration time and so on. (II) Analysis of membrane formed by Goji extracts includes stickiness and glass transition temperature. (3) Estimation of high viscosity extraction system：This study uses concentration, temperature, pH value and content of metal ions as the independent variables to examine the viscosity and the feasibility of fluid bed granulation. (4) Estimation of operational parameters of binder：This study uses (I) starch and (II) starch and Goji extracts as binders to examine the physicochemical properties, membrane formability and moisture-absorbing properties. (5) Estimation and modification of new granulation technology：This study is separated into two parts, (I) operational parameters of fluid bed granulation and (II) estimation and modification of granules. (I) Operational parameters of fluid bed granulation includes dimensionless spray flux, penetration time, binder import rate and inlet air temperature. (II) Estimation and modification of granules includes particle size, color analysis, SEM, moisture content, water activity, X-ray, DSC, glass transition temperature, solubility, swelling power and coating ratio of polysaccharide. (6) Development and improvement of anti-caking technology: This study is separated into three parts, (I) caking mechanism, (II) changing the composition of binders and (III) estimation of anti-caking technology. (I) Caking mechanism includes establish caking mechanism (glass transition temperature, moisture content, water activity and surface energy), powder rheology, morphology, growing rate of particle size and loading efficiency. (II) Changing the composition of binders includes starch, edible gum and maltodextrin and the establishment of the parameters of temperature and humidity. (III) Estimation of anti-caking technology uses estimates of the pharmaceutical factory.