The Hong Kong Polytechnic University 香港理工大學

1. NEW ORIENTATIONS OF RESEARCH IN CHINESE MEDICINES 位於深圳的科研設施 The Hong Kong Polytechnic University 香港理工大學

2. ExtendedPlatform擴展的科研平台 PolyU Institute of Modern Chinese Medicine 理工理大現代中藥研究所 PearL Materia Medica Development (Shenzhen) Ltd. [PMMD] 普爾藥物科技開發(深圳)有限公司 [普爾] State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, China 深圳市中藥藥學及分子藥理學研究重點實驗室 (省部共建國家重點實驗室培育基地)

3. Introduction 簡介 • PMMD is the subsidiary of The Hong Kong Polytechnic University (PolyU) to expand our capacity in the research and development of new drug and the related technologies 普爾由理大全額投資興建，以擴展新藥研發及相關技術的能力 • It was set up in Shenzhen Hi-tech Industrial Park in July 2001and has beenfully operated since April 2002 研究所位於深圳高新科技園，01年7月成立，02年4月正式投入服務 • It is an upgraded research platform for drug discovery and providingcontract research services to the industry 研究所成為新藥開發的一個高水平的技術平臺，並為企業提供合約型式的研究服務

4. Situated at: the southern end of Hi-tech Industrial park in Nanshan District of Shenzhen 位於深圳高新科技園南區 Invested by: The Hong Kong Polytechnic University

5. Mission 宗旨 • Modernization of Traditional Chinese Medicine (TCM) in Hong Kong and the Chinese mainland in formulation, quality control, safety and efficacy evaluation to enhance the acceptance of TCM by the global market 通過現代化製劑、安全療效評價、質量控制等手段，促進中港兩地中藥現代化的發展，提升中藥於國際市場的認受性 • Commercialization of bio-chemical technologies and promotion of Hong Kong as a research and development (R&D) centre for TCM 促進化學生物科技轉化，使香港成為中藥產品研發中心 • Promotion of R&D of innovative medicine and advanced pharmaceutical technology in the industry 推廣開發藥物的新技術，提高業界的新藥研製水平

6. Standard Laboratory with an total area of 2000m2 總面積超過2000平方米 SPF Animal Lab 無特定病原 動物實驗室 Molecular Pharmacology Lab 分子藥理 實驗室 Analytical Lab 儀器 分析室 Pharmacology Lab 藥理 實驗室 Toxicology Lab 毒理 實驗室 Formulation Lab 製劑實驗室 TCM Chemistry Lab 中藥化學 實驗室 Chiral Lab 手性化學開放實驗室 Conference Room 會議室 NMR 核磁 共振儀

7. Research Facilities 科研配套 TCMFormulation製劑 TCM Chemistry 化學 Toxicology Studies毒理 Pharmacology Studies藥效

8. TCM Chemistry 中藥化學

9. TCM Formulation中藥製劑

10. Toxicology and Pharmacology Studies毒理及藥理測試

11. SPF Animal Laboratory 無特定病源級動物實驗室 SPF Animal Laboratory is built according to the “National Standard of the Quality of Laboratory Animal of PRC (1999)” 《中國實驗動物質量國家標準》and is accredited the “Guangdong SPF Grade Laboratory Animal Facility Certificate” 「廣東省無特定病源級動物實驗設施証書」 (2002-2005)

13. Key Personnel領導

14. Prof. Albert S. C. Chan 陳新滋 教授 Prof. Georges M. Halpern Prof. T. H. Chan 陳德恆 教授 Prof. K. Y. Wong 黃國賢 教授 Dr. M. S. Wong 黃文秀 教授 Prof. S. L. Chen 陳士林 教授 Prof. D. J. Yang 楊大堅 教授 Prof. T. Ye 葉濤 教授 Prof. Z. M. Qian 錢忠明 教授

15. Scope of Research研究領域

16. Raw herb resourcessurvey / Authentication of raw materials (distinguish between confused, fake & substitute items) 資源調研/藥材鑑別 (真偽、混淆品、代用品) • Quality assessment on raw materials and preparation of Chinese Medicine 原藥材或製劑的品質評價 • Establishment of quality control standardsand biological indicators製定品質控制指標及生物指標 • Isolation and structural elucidation of the active components for bioactive screening分離活性成份 • Application of modern technologies in formulation 現代製劑技術的應用 • Efficacy and toxicology studies of TCM formulations 藥物藥效/毒理等臨床前測試

17. Authentication / Quality Assessment 藥材鑑別 / 品質評價/ 品質控制 • Thin-Layer Chromatography (TLC) 薄層掃描色譜分析儀 • High-Performance Liquid Chromatography (HPLC) 高效液相色譜儀 • Gas Chromatography (GC) 色氣相色譜儀 • Qualitative Identification 質化 (Chromatographic Fingerprint evaluation) • Quantification of marked ingredients量化 (UV, TLC scanning, HPLC, GC)

18. Quality Control of TCM中藥質控技術 • Good Agricultural Practice (GAP) in cultivation of raw herbs 藥材生產管理規範以生產優質藥材 • Application of chemical (HPLC) and DNA fingerprinting to provide comprehensive component analysis 利用指紋圖譜技術有效控制藥材品質

19. Herbs with Comprehensive Studies 經深入研究之藥材 • Radix Puerariae葛根 • Herba Epimedii淫羊藿 • Fructus Alpiniae oxyphyllae益智 • Radix Salviae miltiorrhizae丹参 • Rhizoma Polygonati odorati玉竹 • Radix Rubiae茜草 • Semen Cassiae决明子 • Rhizoma Cimicifugae升麻 • Fructus Schisandrae五味子 • Herbal Dendrobii石斛 • Radix Astragali黄蓍 • Ramulus Uncariae cum uncis钩藤

20. Bioactivity Assay Antioxidant activity Biological active compounds 尾葉遠志 Polygala caudata 細葉遠志 Polygala tenuifolia Screeningfor Active Ingredients 分離活性成份

21. Hong Kong Chinese Materia Medica Standards香港中藥材標準 • Content of study研究內容 • General description一般描述 • Microscopic identification顯微鑒定 • Chromatography (HPLC, TLC, GC)色譜分析 • Determination of heavy metal, pesticide residues, mycotoxins, foreign matter, ash, water content and extractives重金屬、農殘、霉菌毒素、雜質、灰分、水分和提取物的測定 • GC and HPLC fingerprints氣相和高效液相指紋圖譜

22. Spica prunellae Common selfheal夏枯草

23. Rhizoma atractylodismacrocephalae白術

24. Application of Modern Formulation Technologies現代製劑技術的應用 • Osmotic pump controlled release technology滲透控釋技術 • Macroporous resin refining technology大孔樹脂分離技術 • Phospholipids complex technology磷脂質製劑技術 • Solid dispersion technology固體分散技術 • Cyclodextrins inclusion technology • Supercritical fluid extraction超臨界提取技術 • Spray-drying, freeze-drying, film-coating 噴霧乾燥技術,冰凍乾燥技術, 薄膜包衣技術

25. Efficacy test – arthritis product 藥效測試－關節炎藥品 • Testing Models：產品治療痹證 (關節炎) 的藥效學研究 • Adjuvant-Induced Arthritis in Rats (30 days) • 對大鼠佐劑性關節炎的影響 • measure the primary and secondary paw edemas; and the arthritis index佐劑誘導佐劑關節炎，量度原發及繼發性的足腫，和關節炎指數 • 2. Cotton-Induced Outgrowth in Rats (14 days) • 對大鼠棉球肉芽腫的影響 • measure the dry weight of cotton pellet induced granuloma • 植入滅菌棉球，觀察棉球肉芽腫的重量 • 3. Acetic Acid Induced Body-Twist Model in Mice (10 days) • 對小鼠醋酸扭體反應的影響 • observe the frequency of body twisting in mice after the injection of acetic acid mixture 注射醋酸生理鹽水溶液，觀測小鼠扭體的隻數和次數

26. Efficacy test –slim product 效用測試-減肥保健品 • Animal Model (Nutritious Obesity) : • 減肥藥對大鼠營養性肥胖的治療作用: • SPF grade Rats feeding with high energy diet for 30 days; Observe for • the Testing Criteria after the administration of product for conse. 28 days • 高能量飼料餵養SPF級大鼠30天後，給藥28天並觀察指標 • Testing criteria (檢測指標)： • （1）Body Weight (Daily) 體重 (每天) • （2）Lee’s Index Lee’s 指數 • （3）Weight of Adipose Tissues 體內脂肪重量測定 • （4）Determine the size of fat cells 脂肪細胞大小的測定 • （5）Blood Lipid (serum CHL, TG, HDL, LDL) • 血脂 (血清總膽固醇、甘油三酯、高密度脂蛋白、 • 低密度脂蛋白和極低密度脂蛋白)

27. Safety Evaluation 安全性測試 • Acute Toxicity 急性毒性試驗 • Chronic Toxicity 長期毒性試驗 • Genetic Toxicity 遺傳毒性試驗

28. Product Development產品開發

29. Cardiovascular diseases心血管疾病 • JCM01021/JCM01023 • Single compound單體 • For myocardial ischemia/angina治療心肌缺血／心絞痛 • Poor bioavailability and only available in injection form低生物利用度，只有注射劑 • Modification by a) phospholipids complex formation; b) structural modification改良方法a)磷脂複合；b)結構修飾 • US, PCT and China patent filed己申請美國、PCT和中國專利

30. JCM01022 • Compound formula consisting of the active fractions of two herbs由兩味中藥有效部位組成的複方 • For hyperlipidemia治療高脂血症 • Good comprehensive blood lipids modulating effect良好綜合調節血脂作用 • China and PCT patents filed已申請中國和PCT專利

31. Rheumatoid arthritis類風濕關節炎 • Compound formula based on triptolide以雷公藤甲素組成的複方 • Triptolide is an effective immunosuppressant with strong adverse drug effect雷公藤甲素是有效的免疫抑制劑，但有強烈的副作用 • To screen for suitable active compounds in herbs to reduce the toxic effects of triptolide and increase the inflammation inhibitory effect篩選合適的中藥有效成分，起增效減毒之用

32. Development of New Drug/ Functional Food中藥新藥/ 保健品開發 • R&D focus on Chronic Diseases / Autoimmune Diseases with outstanding beneficial effects when using Chinese Medicines: • Cardiovascular Diseases • Myocardial ischemia • Hyperlipidemia • Rheumatoid Arthritis / Arthritis • Osteoporosis • Cancer • Gout • Primary Screening for the New Drug Development • 研發主要針對中藥有較佳治療效果的慢性病 / 自身免疫疾病: • 心血管疾病 • 心肌局部缺血 • 高血脂症 • 類風濕性關節炎 / 關節炎 • 骨質疏鬆症 • 癌症 • 痛風 • 新藥開發的前期篩選

33. Formulation 制劑 Development of CVD Drug 開發心血管藥物 GAP Study 中藥材生產品質管制規範 Medicinal Plant Survey藥用植物研究 Drug Metabolism 藥物代謝學 Safety Evaluation 毒理、安全性測試 Pharmacology Study 藥理藥效學 Clinical Testing 人體臨床測試 Registration註冊

34. Future Direction未來研究方向

35. R&D of functional food based on Chinese Medicine中藥功能食品/保健品的開發 • Application of advanced technology in TCM research • 領先科技的應用 • 3) New interdisciplinary applications of Chinese Medicine • 中藥的跨領域運用

36. Interdisciplinary Study 多方面的研究 • Structural modification of naturally occurring compounds to increase the efficacy and/or decrease the toxicity 有效成份結構修飾以增強效用/減少毒性(Organic synthesis) • Textiles (including mosquito nets) impregnated with insect repellent Permethrin, using nanotechnology驅蚊功能的成衣 (Textile) • Control of cataract development in aged subjects with TCM-derived extracts中藥用於老年白內障的研究(Optometry) • Cordyceps extracts to improve endurance and performance in athletes 冬蟲草增強運動員耐力及表現的研究 (Sports Nutrition) • Development of a TCM-derived fungicide to control mold invasion and dissemination from filters of sealed building air-conditioning systems以中藥提煉的殺真菌劑用於中央空調系統(Building)

37. Mind Map for the Development of Chinese Medicine Research Directions Deliverables Advanced technology for TCM research • Area of Excellence: • Drug discovery and Synthesis • Chinese Medicine Research Upgrade the standard of technology used for testing & manufacturing of TCM products Existing Strength New interdisciplinary applications of Chinese Medicine Novel and innovative applications of TCM State Key Laboratory in Chinese Medicine and Molecular Pharmacology Development of high-quality TCM-based functional food targeted for both national and international market R&D of functional food based on Chinese Medicine Development of TCM based drugs targeted for both national and international market Interdisciplinary Research Expertise in biology, chemistry, biotechnology, engineering, health sciences and food sciences at PolyU New drug development based on Chinese Medicine Interdisciplinary training platform for students Provide well-trained professionals for supporting development of the TCM industry

38. Achievement成就

39. State Key Laboratory 國家重點實驗室 PMMD has been recognized as the “Shenzhen Key Laboratory for Formulation, Toxicology and Pharmacology”since October 2003 普爾於2003年10月獲認可為 “深圳市重點實驗室 - 製劑、毒理 及 藥理” It has been further recognized as the “ State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, China”since January 2005 普爾於2005年1月獲認可為 “深圳市中藥藥學及分子藥理學研究重點實驗室”

40. State Key Laboratory in Chinese Medicineand Molecular Pharmacology (SKL) Phase I 1. Establish high technology platform for quality assurance of TCM 2. Establish a platform for functional fingerprinting of TCM 3. Develop a pipeline of functional food products, TCM formula and new drugs 4. Provide interdisciplinary training for both graduate and undergraduate students 5. Provide technical assistance and assist in modernization of Hong Kong TCM industry 6. Elevation of the SKL status at the national level Phase II • 1. Transfer of technology to industry for quality assurance of TCM • 2. Develop biosensors and analytical methodologies for high throughput drug screening • 3. Develop a pipeline of functional food products, TCM formula and new drugs • 4. Establish partnership with multinational companies for R&D of TCM products • 5. Develop SKL into a high impact world center for TCM research and development Development Roadmap 發展路線圖 AOE in Drug Discovery and Synthesis AOE in Chinese Medicine and Further Development Institute of Modern Chinese Medicine Institute of Materia Medica Shenzhen Key Laboratory in TCM Formulation • 2002 2003 2004 • 2005 2006 2007 2008 2009 2010 2011

41. Contact (Hong Kong) 香港聯絡處 聯絡人: 黃慧賢 小姐 電話: 852-34008694 電郵: trhelen@inet.polyu.edu.hk 網頁: www.pearlsz.com 地址: 香港九龍紅磡香港理工大學 Y829室 Contact Person: Ms. Helen Tam Telephone no: 852-3400-8694 Email: trhelen@inet.polyu.edu.hk Website: www.pearlsz.com Address: Y 829, The Hong Kong Polytechnic University, HungHom, Kowloon, HK

42. Contact (Shenzhen) 深圳聯絡處 聯絡人: 何翠君 小姐 電話: 86-755-26737462 電郵: bcjoyce@inet.polyu.edu.hk 網頁: www.pearlsz.com 地址: 中國深圳市南山區 高新科技園南區R2-A棟6/F Contact Person: Ms. Joyce Ho Telephone no: 86-755-26737462 Email: bcjoyce@inet.polyu.edu.hk Website: www.pearlsz.com Address: 6/F A District R2 Building, Hi-tech Industrial Park, Nanshan District, Shenzhen, Guangdong, China