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Box 300, 1400 Vienna, Austria Tel: (+43-1) 26026-0 · www.unido.org · [email protected] Dis tr_ LIMITED PP0.47 UNITED NATIONS 25 August 1987 INDUSTRIAL DEVELOPMENT OtlGANIZATION Original: ENGLISH BEITER UTILIZATION OF MEDICINAL PLANTS: THE PHVTOPHARMACEUTICAL SUPPLY SYSTEM IN CHINA Sectoral Studies Series No.35 SECTORAL STUDIES BRANCH STUDIES AND RESEARCH DIVISION V.87·89009 ... --------------------------------~------------ -- - ~lain results of the study work on industrial ~~ctors are presented in the Sectoral Studies Series. [n addition a series of Sectoral Working Pcpers is issued. This document presents major results of work under the element Pharmaceutical Industries in :.:'.'HOO' s prngr:imme of Studies and Research 1986/87. i_________ _ This document has been reproduced without formal editing. The designations employed and the presentation of matedal in this document <lo not imply the express Lm ..Jf any opinion whatsoever on the part of the Secretariat of lJNIDO conr.c.rning the legal status of an~· country, territory, city or area or of its authorities, or concerning the delim~catinn of its frontiers or boundaries. :-tention of company names and r.ommerc!.al products does not imply the endors~.~nt of CNIDO. All parts of this document may freely be adapted, translated, or af.ed 10 any form for purposes other than prot it making 1rnly approj)riate ref(.:renci:: should be made to the source. - i - I II Pref ace This study advocates the cultivation and industrial processing of careiully selected medicinal plants under controlled conditions in developing countries as the only alternative to provide crude drugs and phytopharmaceutical preparations that meet all basic criteria for essential drugs. The establishment or expansion of a phytopharmaceutical industry has economic advantages, in addition to the social benefits, through the better utilization of domestic resources and potential reduction of imports. It contributes also to the evolution of domestic R+D capability in agronomic, agrotechnical, chemical, medical and pharmaceutical sciences. Medicinal plants represent also an under-utilized reservoir of new and novel drugs that could be used in the treatment of diseases prevailing in developing countries. This study has been carried out in the Sectoral Studies Branch by Mr. Janos Pogany. The Branch wishes to ackno~ledge the contribution of Mr. R~n Dequan, Vice General Manager, China Natj~nal Corporation of Traditional and Herbal Medicine, State Pharmaceu:ical Administration of China, for the provision of essential technical, ecuncmic and market data on the phytopharmaceutical indust1y in the Pe•_ pie's Republic of China as well as for the consultations on the Chinese experience in the course of this work. Contents l. INTRODUCTION l 2. BACKGROUND 2 3. OBJECTIVES 3 4. LITERATURE REVIEW OF THE HERBAL PHARMACEUTICAL INDUSTRY WORLDWIDE 4 4.1 Medicinal plants 4 4.2 Essential oils and pharmacopeial phytopharmaceuticals 11 4.2.l Essential oils 11 4.2.2 Pharmacope~~l phytopharmaceuticals 13 4.3 Conclusions 13 5. THE PHYTOPHARMACEUTICAL INDUSTRY IN CHINA 15 5.1 General statistical considerations 15 5.2 Industrial and market statistics 16 5.3 Collection and cultivation of plants 20 5.3.1 General aspects 20 5.3.2 The Chinese achievements 21 5.4 Industrial technology for the production of phytopharmaceuticals 22 5. 4. 1 From crude drug to extracts 23 5.4.2 Extraction 23 .. 5.4.3 Manufacture of phytopharmaceutical preparations 24 5. 4 .1~ Quality control 25 5. 5 Research and developmerat 26 5.5.1 Cultivation of plants 26 5.5.2 Cell cultures 26 5.5.3 Standardization of crude drugs 27 5.5.4 Process development 28 5.5.5 New drugs 28 5.6 Conclusions and implications 33 6. G~NERAL CONCLUSIONS 35 - .lV - 7. RECOMMENDATIONS 37 7.1 Domestic production 37 7.2 International co-operation 37 Annex l Illustrative contents of a phytopharmaceutical registration dossier 39 Annex 2 Medicinal plants in the official Chinese paramedical manual 40 Annex 3 Technical description of a small-scale phytopharmaceutical factory 51 Bibliography 57 Tables 1. Phytopharmaceutical R+D in the Philippines 8 2. Sales 1975-1986 of pharmaceuticals and traditional drugs in China 16 3. Production statistics 1957-1986 of Chinese traditional pharmaceutical factorie& 17 4. Typical 25 Chinese traditional drug preparations 18 s. Structure of typical R+D expenditures 20 A. l. Water consw1:ption 53 A.2. Power supply consumption 53 A.3. Main process equipment 54 - V - J VI Figures 1. Computerized selection of medicinal plants for domestic cultivation 10 2. Historical trend in the exchange rate of the Chinese national currency 15 3. Schematic illustration of the production of crude drugs 22 4. Flow diagram of the extra~tion process 24 5. Flow diagram of the manufacture of honey-pills 25 6. Ginsenoside Rb1 27 7. Chemical structure of qinghaosu and its derivatives 28 8. Chemical structure of gossypol 29 9. Chemical structure of henbane alkaloids 30 10. Chemical structure of THP and stepholidine 11. Antitwnor agents of cephalotaxus 32 - ..-ii - EXPLANATORY NOTES References to dollars ($) are to United States dollars, unless otherwise stated. A conma (,) is used to distinguish thousands and millions. A full stop (.) is used to indicate decimals. A slash between dates (e.g., 1980/81) indicates a crop year, financi~l year or academic year. Use of a hyphen between dates (e.g., 1960-1965) indicates the full period involved, inciuding the beginning and end years. Metric to.1s have been used throughout. The foil~wing forms have beea used in tables: Three dots( ••• ) indicate that data are not available or are not separately reported. A dash (-) indicates that the amount is nil or negligible. A blank indicates that the item is not applic~ble. Totals may not add up precisely because of rounding. Besides the conman abbreviations, symbols and terms and those accepted by tne International System of unit~ (SI), the following abbreviations and contractions have been used in this report: PRC People's Republic of China SPAC State Pharmaceutical Administration of China Rmb Renminbi EEC European Economic Conmunity R+D Research and development GMP Good manufacturing practices WHO World Health Organization of the Uoitad Nations FAQ Food and Agriculture Orgar.ization of the Unit~d Nations ------------------------------------------ - •ri ii - KEY WORDS For the purpose of this study, certain repeatedly used terms are defined as follows: CRUDE DRUG is a fresh or dried medicinal plant, or ?arts thereof. ESSENTIAL OILS are flavouring agents, a sub-group of pharmaceutical necessities, obtained from natural source materials mainly of botanical origin. HERBS are flowering plants containing chemical substances which may have a therapeutic action. HERBAL REMEDIES (herbal preparations) are finished or partially finished herbal products manufactured on an industrial scale and markeced without regulatory evidence of efficacy and safety. MEDICINAL PLANTS are higher plants (unicellular plants, e.g., yeasts, green algae, etc .. excluded) containing chemical substances which have a proven and established medicinal action. MEDICINE is the science and art of restoring and preserving health. MODERN MEDICINE is the system of medicine practised by physicians. PHARMACEUTICAL NECESSITIES (pharmaceutical aids, auxiliary substances, inert materials, additives, added substances, axcipients) are substances that are of little or no therapeutic value but which are useful in the manufacture and compounding of various pharmaceutical preparations. The subgroups of pharmaceutical necessities are (i) antioxidants and preservatives, (ii) colouring, flavouring and diluting agents, (iii) emulsifying and suspending agents, (iv) ointment bases, (v) pharmaceutical solvents, and (vi) miscellaneous pharmaceutical necessities. PHYTOPHARMACEUTICAL PREPARATION (phytopharmaceutical product, phytotherapeutic specialty, herbal pharmaceuticals) is the safe and effecti.ve finished, or partially finished (e.g. yingpian) product