Phytomedicines: Bioactive Compounds from Plants

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Phytomedicines: Bioactive Compounds from Plants
Outline
1. Introduction
2. Phytomedicinal molecules
3. Policy and Research
4. Pascual R&D
Phytomedicines: Bioactive
Compounds from Plants
Let food be your medicine and medicine
your food.
Objective: Broader appreciation of plant
medicinal chemistry and deeper
understanding of what phytochemical
research is all about
Dr. Gani Padolina, Director for R&D
24Jul12
Hippocrates, 400 BC
Agriculture and Food Canada, 2006. Functional Foods
and Nutraceuticals. http://www.agr.gc.ca./misb/fbba/nutra/index_e.php?page=intro.
MAP Seminar
July 2011
History
Plant Biosynthesis
Prehistoric
•4000 B.C. – Cradles of Western Civilization by the Eufrat and Tigris
•3000 B.C. - 800 recipes/700 plants from Egypt
•3000 B.C. – Pen Tsao documents from China
CO2 + H2O + N,P,K + Trace Elements +Light
Greek-Roman Period
•460-377 B.C.- Hippocrates (60 medicinal plant recipes)
•129-200 A.D. – Galenus (130 medicinal plant recipes)
Primary Metabolism
Carbohydrates, Lipids,
Proteins
Arabic-Monastery Period
•980-1037 A.D. – Avicenna (Pharmacy system for medicinal plants)
•1493-1541 – Paracelsus (Clinical studies)
Plants are Prolific Biochemistry and
Organic Chemistry Laboratories
Scientific Period
•1700s – Carl Von Linne (Plant Systematics)
•1900s – Sir Alexander Fleming (Penicillin)
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Paulsen, 2010 (DNVA)
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Secondary
Metabolism
Flavonoids, Phytoalexins,
Alkaloids, Phenylpropanoids,
Phenolics, Terpenoids, etc.
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Quinine from Chicona calisaya
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Plant Biochem, Univ of Kentucky
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Anti-malarial
Anti-pyretic
Analgesic
Anti-inflammatory
Discovered by Quechua
Indians from Quina-quina
(cinchona) bark
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Quinine
BASIL
Smith and Williams/Rabe
synthetic route
Alkaloid Biosynthesis
Basil (Ocimum basilicum):
•allylalkoxybenzene estragole
•metabolised to the proximate carcinogen 1′hydroxyestragole by P450 enzymes
High heat, organic solvents
and acid
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Room temperature, water,
physiological pH
Smith and Williams, 2008
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Jeurissen et al., 2008
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Hall, 2007
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Potato
• Starch - Beneficial
• Glycoalkaloids: Solanine and
chaconin- Teratogens
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Weckwerth, 2003
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July 2011
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Sampung Halamang Gamot - DOH
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Blomhoff, 2010 (DNVA)
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LAGUNDI (Scientific name: Vitex negundo) – Gamot sa ubo, sipon, lagnat, at hika
YERBA BUENA (Scientific name: Clinopodium douglasii) - Gamot sa pananakit ng
katawan, ubo, sipon, hilo, at pangangati
SAMBONG (Scientific name: Blumea balsamifera) – Gamot sa high blood (hypertension)
bilang isang pampaihi o diuretic; nakakalusaw ng mga bato sa bato.
TSAANG GUBAT (Scientific name: Carmona retusa) – Gamot sa sakit ng tiyan o pagtatae
(gastroenteritis) at pangmumog para maiwasan ang mga cavites o pamumulok ng ngipin.
NIYOGNIYOG-NIYOGAN (Scientific name: Quiscalis indica) – Gamot sa bulate sa tiyan
AKAPULKO (Scientific name: Cassia alata) – Panlaban sa mga fungal infection sa balat
gaya ng an-an, buni, alipunga.
ULASIMANGULASIMANG-BATO (Scientific name: Peperonia pellucida) – Ginhawa sa rayuma
o arthritis at gout
BAWANG (Scientific name: Alium sativum) – Pampababa ng kolesterol (cholesterollowering agent)
AMPALAYA (Scientific name: Momordica charantia) – Pampababa ng asukal sa dugo sa
mga may diabetes (Lowers blood sugar levels)
BAYABAS (Scientific name: Psidium guajava) - Gamot sa pagtatae (antidiarrheal) at
panghugas ng katawan na nakakaalis ng mikrobyo (antiseptic).
July 2011
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PascualLab Commitment to Quality Healthcare Products
Traditional and Alternative Medicine Act of
1997 (TAMA Law): RA 8423
• “to improve the quality and delivery of health care services
to the Filipino people through the development of
traditional and alternative health care and its integration
into the national health care system.”
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Good Agriculture Practices (GAP)
WHO/FDA Guidelines
Good Manufacturing and Laboratory
Practices (GMP and GLP)
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All-Natural and Organic Farming
Sterilization
Rapid Micro Testing
Extract Standardization
Efficient and High Volume Extraction
Closed System Manufacturing Process
Blumea balsamifera L.
FARM
MARKET
DEDICATED HERBAL
RESEARCH & PRODUCT
DEVELOPMENT
Leonie Agri Corp
DEDICATED
MANUFACTURING
MARKETING
• Secretary Juan Flavier and Senator Edgardo Angara
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Value Creation at all Levels
Take Home Message
absorbance
Continuous Improvement:
From Initial Technology Transfer to 3rd Generation
Process
• RA 7394 (Consumers Act of the Philippines): “Drug”
includes all herbal plants listed in the Philippine National
Drug Formulary
March 2012
time
Confidential
Backup
• Bioactive compounds: secondary metabolites with
pharmacological effects
• Variety of factors influencing metabolic profiles
• R&D Essential:
– To determine effect of different farming methods, different
harvest times
– To leverage plant chemistry for integrated crop and pest
management
– To support the growth of the Philippine herbal industry via
meaningful standardization and clinical studies
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PascualLab Commitment to Quality Healthcare Products
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Standardization Efforts
Good Agriculture Practices (GAP)
WHO/FDA Guidelines
Good Manufacturing and Laboratory
Practices (GMP and GLP)
Soil Chemistry
•Fertilizer
•Beneficial
Micro
•Water
Harvest
•Mother Plant
•Plant sections
•Age
Post- Harvest
•Washing
•Cutting and
Drying
•Storage
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We are proud of……
of……
Manufacturing
•QC/QA
•Std Process
•GMP
• Managing consistency amidst many
variables
• Continuous efforts on Sambong R&D
• Leader in process standardization
• Analytical method under GLP validation
Continuous Improvement
2 00
3.862
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39.608
25.994
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12.971
20
3.130
3.328
4.310
4.806
5.409 5.118
5.765
6.459
50
10
9.393
0
10.786
75
0
29.901
39.608
1 00
25.994
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1 25
29.901
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3.130
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21.496
14.323
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10.786
absorbance
m AU
20 0
16.229
All-Natural and Organic Farming
Sterilization
Complete Micro Testing
Plant Material Standardization
3.862
DAD1 A, Sig =28 5, 4 Ref=360 ,1 00 (SMB06 2FP\00 4-04 01 .D)
mAU
DA D1 A, Sig =28 5 ,4 Ref=3 6 0,1 00 (SM B0 62 FP\0 04 -0 40 1 .D)
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10
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30
40
50
min
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Guidelines for Drug Substance Impurity Thresholds
Examples of
Functional Food Components
Maximum
Daily Dose
Reporting
Threshold
Identification Threshold
Qualification Threshold
≤ 2g/day
0.05%
0.10% or 1.0mg/day
intake (whichever is
lower)
0.10% or 1.0mg/day
intake (whichever is lower)
0.05%
0.05%
> 2g/day
0.03%
Functional
Components
Source
Potential Benefits
Major Classes of Phytochemicals
• Add some slides on phytoalexins, insect insect interaction, tree
signalling etc.
Carotenoids
Alpha-carotene
Beta-carotene
Carrots, fruits, vegetables
Neutralize free radicals which
may cause damage to cells
Lutein
Green vegetables
Reduce risk of macular
degeneration
Lycopene
Tomato products (ketchup,
sauces)
Reduce risk of prostate cancer
Reduce risk of breast or colon
cancer
Dietary Fiber
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Important Concepts
• How are phytoactives produced?
• Activity (Medicinal and Toxicity) is dose- dependent
• G x E (Gene Expression and Environmental Factors)
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Insoluble Fiber
Wheat bran
Beta-Glucan
Oats, barley
Reduce risk of cardiovascular
disease and some cancers.
Soluble Fibre
Psyllium
Reduce risk of cardiovascular
disease.
July 2011
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