Cancer prevention and Herbal , Complementary Medicine

1. Presented by : Dr Ling Sien Ngan Anti Aging medical practioner Lowel Anti aging & aesthetic center 27A Jln SS2/75, 47300 PJ. GLOBAL & LOCAL SCENARIOS OF HERBAL/PHYTOCHEMICAL INDUSTRY Chemical Engineering Pilot Plant Universiti Teknologi Malaysia *Materials- courtesy of CEPP

2. ISSUES OF THE 21 ST CENTURY ISU-ISU ABAD KE-21

3. ISSUES OF THE 21 ST CENTURY CHRONIC DISEASES

5. WHEN WILL WE CURE CANCER ? ISSUES OF THE 21 ST CENTURY

6. CANCER ISSUES OF THE 21 ST CENTURY

8. 2003 Global Estimates of HIV and AIDS Source : Population Reference Bureau , 2005

10. OBESITY ISSUES OF THE 21 ST CENTURY

14. Stay Young??

15. Food

16. What’s happening to our food industry?

17. Medicine TRADITIONAL MODERN

18. vs Wellness Industry Sickness Industry

19. Introduction to Complementary Alternative Medicine Acupuncture Thai massage Japan hot bath Jamu Indonesia Ayurveda Mandi lulur Bali

23. HERBS then as Traditional and now a Complementary Alternative Medicine Herbs and botanicals have been used for centuries for a variety of ailments. Growing interest in alternative medicine and natural remedies to modern medicines has led to a dramatic growth in the herbal market over the last decade. But herbs increasingly finding application in a variety of foods being promoted on a health platform. (Leatherhead Food Research Association)

28. SCOPE OF THE HERBAL INDUSTRY Herbal Products Industry Insect Repellant, Pesticides & Household Items Industry Insect Repellant, Pesticides & Household Items Industry Cosmetics/ Cosmeticeuticals & Toiletries Industry Cosmetics/ Cosmeceuticals & Toiletries Industry Essential Oils, Flavours Colours & Fragrance Industry Essential Oils, Flavours Colours & Fragrance Industry Healthcare/ Nutraceutical Industry Healthcare/ Nutraceutical Industry Biopharmaceutical Industry Biopharmaceutical Industry Pharmaceutical Industry (Drugs & excipients ) Pharmaceutical Industry (Drugs & recipients ) Herbal/ Traditional Medicine Industry Herbal/ Traditional Medicine Industry M i GHT M i GHT

30. GLOBAL SCENARIO

34. M i GHT M i GHT Herbs and medicinal plants are mainly used for phytomedicines , flavours and fragrance, biopesticides and pharmaceuticals / nutraceuticals . Market growth in medicinal herbs and botanicals was to an average of 7.6% a year between 1999 and 2002. Worldwide sales figures for herbal remedies in year 2000 and projection figures for year 2002 are as follows: Global Trends HERBAL INDUSTRY Billion US$(retail prices) 2001 2002  Europe 6.9 7.5  Asia 5.1 6.2  North America 3.9 4.3  Japan 2.3 2.6  South America 0.6 0.8  Australia / New Zealand 0.3 0.4  Mid East 0.1 0.1  Africa 0.1 0.1  RoW 0.3 0.4 Total Value 19.6 22.4 Estimate based on IMS market analysis for 1997 plus main growth rates and side markets

35. Unmistakable trends US 1998 0 2 4 6 8 10 12 14 16 18 Acupuncture Hypnosis Homeopathy Aromatherapy Spiritual healing Chiropractic Massage Herbal remedies Relaxation therapy Percentage of population using therapy 42.1 % used a CAM therapy US$21.2 billion spent 6.29 million visits CAM has become more popular, as is evident in these figures that shows the popularity of various healing methods “ New Scientist's ”

36. Unmistakable trends ENGLAND 1999 0 2 4 6 8 10 12 14 16 18 Acupuncture Reflexology Aromatherapy Chiropractic Osteopathy Massage Herbal remedies Percentage of population using therapy 28.3% used a CAM therapy £ 450 million spent in UK 50,000 CAM practitioners in UK 12.7 million visits in UK Homeopathy “ New Scientist's ” CAM has become more popular, as is evident in these figures that shows the popularity of various healing methods

37. US Herbal and Plant Product Sales Sales, US$ Source: China Economic Information Network, 2003 441,502,560 Total 2,950,132 Kava Kava 3,037,672 Milk Thistle 4,555,723 Bilberry 6,104,450 Valerian 6,182,210 Cranberry 7,299,353 Evening Primrose Oil 9,965,772 Grapeseed 18,381,592 Saw Palmetto 38,341,632 Goldenseal 47,774,792 St John's Wort 49,189,576 Echinacea 71,474,288 Garlic 86,048,080 Ginseng 90,197,288 Ginkgo Product

38. LOCAL SCENARIO

40. The total value of the domestic market for herbal and medicinal plants is now estimated to reach up to RM4.55 billion . Industrial uses of herbs in Malaysia MALAYSIAN SCENARIO (Dr Azizol Abdul Kadir, formerly FRIM) RM 4.55 billion Total RM 2.00 billion Herbal Remedies RM 0.95 billion Pharmaceuticals/nutraceuticals RM 1.60 billion Flavour & Fragrance Value Herbal Uses

41. Malaysian Herbal Industry Market Projection vs Target Year Projected Market Value Targeted Local Content % Share 2000 2005 2010 RM 2.0 b RM 3.2 b RM 5.0 b RM 100 m RM 500 m RM 2.5 b 5% 15% 50% HERBAL INDUSTRY M i GHT M i GHT

43. Bioresources Identification of suitable herbs Strategic Analysis-core competencies Strong Competencies Product design & development Primary processing Of herbs (post-harvest Processing) New herbal products marketing End users Natural Bioactive Compounds Development of Required herb for Industry / New Herbal outlets Commercial production of Required herbs Clinical research Manufacturing Distribution Weak Competencies Weak Competencies Weak Competencies Weak Competencies Weak Competencies Weak Competencies Weak Competencies Ref : Malaysian Herbal Industry Outlook (Might ) Strong Competencies Strong Competencies Strong Competencies Strong Competencies Strong Competencies

45. Product Development THE CHALLENGES .... Plantation Harvesting & Processing Product Formulation & Manufacturing Product Marketing Safety, Quality, Standard, Efficacy Raw material sourcing

47. RAW MATERIAL SOURCING AND PLANTATION - QUANTITY, QUALITY, RELIABILITY 1

48. Why the raw material sourcing is important??  Large volume of raw materials needed for getting little product Rose : 60,000 blooms to produce 1 ounce of oil Jasmine : 8,000,000 handpicked flower for 1 kg of oil {France : US$ 15,000 / kg, India : US$ 4,000 / kg} Lavender : 100 kg of lavender for 3 kg of oil Tongkat Ali : 45 kg root for 1 kg extract Pegaga : 15 kg dried leaves for 1 kg extract Kemunting Cina : 15 tonnes of leaves for 1 ounce of vincristine extract Examples :

50. PLANTLETS DERIVED FROM TISSUE CULTURE Source: Dr Ilham,FRIM

51. GOOD AGRICULTURAL AND COLLECTION PRACTICE FLOW OF ACTIVITY 1.Plant identification: species, variety or hybrid 2.Locality identification: suitability of soil and climate conditions 3. Propagation technique 4. Pests and weeds control and other contaminants 5. Harvesting technique 6. Cleaning (Wash) technique 7. Drying Method; sun or oven dry 8. Pack and storage Source: Prof Zhari Bin Ismail

54. Example: Tongkat Ali Planted Under Open Condition Source: Dr Ilham,FRIM

55. Tongkat Ali: under oil palm Source: Dr Ilham,FRIM Tongkat Ali: under rubber tree Tongkat Ali: under coconut tree

56. 3 in 1... Source: Dr Ilham,FRIM

57. HERBS CULTIVATION CASE STUDY ON TURNING PEGAGA (Centella asiatica) Source : Dr. Zainal Abidin, MARDI

59. VARIETIES OF PEGAGA Source : Dr. Zainal Abidin, MARDI

60. Source : Dr. Zainal Abidin, MARDI Chemical contain in 3 major species of Pegaga Variety Chemical contain (mg/g crude extract) Madecassoside Asiaticoside Madecassic acid Asiatic acid Salad 67.8 26.7 12.6 9.8 Nyonya 69.5 31.8 14.5 14.4 Kampong 92.6 41.3 11.7 9.9

61. Planting Weed Control Harvesting Post Harvesting Handling Source : Dr. Zainal Abidin, MARDI

62. Estimated cost of production and return from planting I ha of pegaga ‘Nyonya’ atPaya Rumput. Malacca. Source : Dr. Zainal Abidin, MARDI 3.72 4.68 4.56 3.82 3.52 1.19 Cost/Benefit Ratio 31,256.75 37,376.81 36,155.88 42,786.68 45,899.21 8,862.15 Nett Income (RM) 11,475.81 10,152.26 10,152.26 15,192.97 18,225.79 47,671.28 Total Costs of Production (RM) 6,668.02 5,196.22 5,196.22 6,649.71 7,376.44 12,630.82 Subtotal Costs (RM) - - 6,668.02 - - 5,196.22 - - 5,196.22 - - 6,649.71 - - 7,376.44 1,308.14 1,744.19 9,578.49 Labour Costs (RM) Land preparation Planting Miscellaneous 4,807.79 4,956.04 4,956.04 8,543.25 9,076.10. 35,040.45 Subtotal Costs (RM) - 4,807.79 - 4,956.04 - 4,956.04 - 8,543.25 - 9,076.10 22,790.70 12,249.75 Input Cost (RM) Planting material (RM 2.00/kg) Miscellaneous 42,732.56 47,529.07 46,308.14 57,979.65 64,125 56,533.43 Gross Income (RM2,500/t) 17,093.02 19,011.63 18,523.26 23,191.9 25,650.0 22,613.4 Biomass Yield (t/ha) Ratoon 5 Ratoon 4 Ratoon 3 Ratoon 2 Ratoon 1 Main Crop Items/Crop Harvest

63. Source : Dr. Zainal Abidin, MARDI

64. HERBAL AND PHYTOCHEMICAL PROCESSING 2

65. WOOD OR BARKS FLOWERS SEEDS OR GRAINS LEAVES ROOTS OR RHIZOMES DETERMINE PREPROCESSING NEEDS (DRYING, COMMUNITION ETC.)

68. OVERALL PROCESSING FLOW CHART Harvesting Inspection Cleaning Size reduction Drying Extraction Clean up Fractionation Dried herbal product Pure phytochemical

69. Extraction of Phytochemical Valuable bio active compound Non-bio active compound Extraction process Normal method of processing

70. Chart of Classification and Separation of Plant Material Based on Solvent Polarity and Process (Herbal Approach) Plant Material Solvent Extract filtrate Freeze dried Whole concrete extract Membrane Filtration or Low T vacuum evaporation Whole concentrate extract Water Extract Spray dried Whole powder extract Freeze dried Whole freeze dried extract Spray dried Concentrate extract

71. Chart of Classification and Separation of Plant Material Based on Solvent Polarity and Process (Phyto Approach) Plant Material H2O-Glycerol Extraction Non-Polar compound extraction SFE (Phytonics: Phytosol) Terpenoids Essential Oil (e.g. mono & Esquiterpenes: geraniol, limonese Diterpenoids (Phytol, abietic acid) Triterpenoids (Cucurbitacin) Carotenoids ( β-Carotene, lutien, Zeaxanthin, etc) Multi Solvent Extraction Process Terpenoids (e.g. Menthol, carrone, squalene, α-Carotene, lycopene) Lipids Polar Compound Extraction Flavanoid (e.g. anthocyanin-cyanidin, flavanols- Kaemferol, isoflavanoid-rotenone) Polar alkaloid (e.g. Ephedrine) Sugar & Derivatives (e.g. monosacharide, Oligosacharide, sugar alcol) Fiber Acid Hydrolysis filtrate Cellulose filtrate Hemicellulose filtrate Lignin

72. technology used must be able to produce… MAXIMUM QUANTITY OF PRODUCTS OF HIGHEST QUALITY (eg. ACTIVITY) AT THE LOWEST POSSIBLE COST

73. Raw Materials Product PROCESS Root / Rhizomes Bark / wood Leaves / Vegetables Flower Fruit / seed / nuts Fruit or vegetable juice / medicinal concentrate High-grade alcohol Concrete/Oleoresin Aqueous aroma Essential oil Extraction Of Specialty Chemical From Plant Utilizing Turbo Extractor Distillator

74. TONGKAT ALI EXTRACTION PROCESS RAW MATERIAL EXTRACTION PROCESS FILTERING PURE TONGKAT ALI EXTRACT SPRAY DRIED PROCESS PACKAGING Case study :

75. PROCESS IN THE PREPARATION OF TONGKAT ALI AQUEOUS EXTRACT Source: Dr Ilham,FRIM

76. THE DRYING PROCESS OF TONGKAT ALI AQUEOUS EXTRACT Source: Dr Ilham,FRIM

77. TONGKAT ALI CAPSULES mmbpp (spray dried) Commercial A (saw dust) Commercial B (saw dust mixture) Physical characteristics of Tongkat Ali capsules containing aqueous soluble extract Source: Dr Ilham,FRIM

80. Chemical Profile High Perfomance Liquid Chromatography (HPLC) HPLC Profile Tongkat Ali Pegaga

83. 0 2 4 6 8 10 12 14 16 Discovery (2-10yrs) Phase I 20-80 healthy volunteers used to deterrmine safety and dosage Phase II 100-300 patient volunteers used to look for efficacy and side effect Phase III 1000-3000 patient volunteers used to monitor adverse reactions to long term use FDA review/ approval Compound success rates by stages 5,000 - 10,000 screened 250 5 1 Source: Dr Ilham,FRIM Preclinical testing laboratory & animal testing

84. MARKET VALUE OF HERBAL PREPARATIONS Fresh materials (roots, leaves, etc) Dried powder Non-standardized extract Standardized extract Phytomedicine Freeze/spray dried extracts Value added 4 Product Marketing Source: Dr Ilham,FRIM

85. Example: Price of Pegaga after processing USD 100 Standardization RM40 RM25 RM10 RM2 Freeze-drying Extraction Juice, dried herbs or powder Raw material Ref : Malaysian Herbal Industry Outlook (Might )

86. Final Product – Register with National Pharmaceutical Control Bureau (BPFK) Safe to consume or apply ADA OOHMP!!!

89. HERBAL PRODUCTS IN MALAYSIA MARKET Alterni Clara International Nona Roguy Victus Semulajadi NEW IMAGE OF HERBAL PRODUCTS Source: Dr Ilham,FRIM

90. Source: Dr Ilham,FRIM

91. Source: Dr Ilham,FRIM

92. AKARpull ® Source: Dr Ilham,FRIM