Dr. Daniel K. W. Mok and Dr.

Ray Cooper

ABCT, Y822
daniel.mok@polyu.edu.hk

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 Part I: From Plants to Medicine from a
western perspectives…

 Part II: Drug Development Process &

Clinical Trials

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True or False?

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From artifacts -
ancient farmers used wooden
ploughs with a stone cutting
edge for field cultivating.
These were drawn by cattle
They learnt to plant for
food and discover the
property of some plants
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 Many drugs are originated from plant source
◦ About 25% of chemical drugs nowadays are from
plants
◦ About 60% of anti-tumour and anti-infectious
drugs are of natural origin
◦ Examples of drugs from plants like aspirin (from
Salix species), morphine and codeine (pain
killer from poppy), quinine and quinidine (anti-
malaria drug the from Cinchona spp.), taxol
(anti-cancer drug from Taxus brevifolia)

Toxicon 39 (2001) 603–613 5

Discovery of Aspirin
 Willow bark had been used by the ancient
Egyptians, native Americans or Chinese to relief fever
and pain
 Hippocrates was the one who record the medicinal
use of willow leaves and bark
 Until the 19th centuries, the German pharmacologist
Prof. Johann Buchner isolate salicin from willow bark.
With lots of work on purifications and structure
modifications to reduce the side effects by many
other scientists, acetylsalicylic acid was discovered
by Felix Hoffman and commercialized as the name
“Aspirin” in 1899
 The action mechanism of aspirin was well studied until
1970’s

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Discovery of Aspirin

Extraction
with
alcohol

salicin Structure
Isolation and
modifications
purifications

Aspirin
(acetylsalicylic acid)

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Botanicals are plants with a medicinal function, as
they are originated from plants, the purpose of
them would be:

 For survival (as food)

 For health (to help us healthy)
 For treatment (as drug to treat disease)

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Instead of knowing the herbs by the nature (hot, warm, cool
and cold) or by its flavors (sour, bitter, sweet, acrid, salty),
modern science evaluate the plant by it’s chemical
compositions or nutritional values, they are mainly the
primary metabolites

 Proteins: e.g., amino acids, peptides

 Carbohydrates: e.g. sugar, starch
 Lipids (fat)
 Minerals: e.g. sodium, potassium, calcium, magnesium,
phosphorus
 Vitamins: e.g., vit C, E, B12

All provide the body with energy, metabolism & cell vitality

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Metabolites are intermediates in metabolic
processes in nature - usually small molecules
A primary metabolite is directly involved in
normal growth, development, and reproduction.
Eg fermentation products: ethanol, acetic acid,
citric and lactic acid cell constituents: lipids,
vitamins, polysaccharides
intermediates: amino acids and nucleotides .
enzymes, certain proteins
 Carbohydrates – e.g., glucose, sucrose,
starch
 Lipids – e.g., cholesterol, triglyceride
 Proteins – e.g., peptides, amino acids

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https://www.creative-proteomics.com/services/plant-
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primary-metabolites-analysis-service.htm
 These are the most abundant class of organic
compounds found in living organisms. E.g.,
Cellulose, Starch, Sugar
 They originate as products of photosynthesis,
condensation of carbon dioxide requiring light
energy and the pigment chlorophyll.
n CO2 + n H2O + energy → CnH2nOn + n O2

chlorophyll

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Examples of carbohydrates

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 Lipids are fatty substance that cannot dissolve in
water, they have important function in storing
energy in organisms and structural material for
cell membrane
 Examples of lipids includes cholesterol, fat
soluble vitamins like vitamins A or D, waxes
 It is formed by the process lipogenesis

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 Proteins are large molecules made of long chains
of amino acids, they have various function in
organism including forming enzymes, DNA
replication etc
 Examples of proteins include collagen,
hemoglobin
 Formed by protein synthesis in cell with the
process of transcription and translation

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 Is sand a natural product?
 What is organic?
 What elements are in natural products?
 Where do you find natural products?

 answers:
 Typically C, H, O, N,
 Also S, P
 Terrestrial/Marine/Microbial/Animal

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 A secondary metabolite is not directly involved
in those processes, but usually has a function but
not that important for the organism eg antibiotics,
pigments
Other:
 Alkaloids- e.g, Ephedra (Ma Huang)

 Polyphenols- e.g., Green tea antioxidants

 Terpenes – e.g., Ginkgo

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Biosynthetic pathway of certain classes of plant secondary
metabolites from glucose in plant cells

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Cordyceps Cs-4

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Product Development of Botanicals
From selection of the right plant, sourcing, standardization, safety etc.

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 Dietary Supplements
 Food additives
 Functional Foods
 Medical Foods
 Botanical Drugs
 Drugs and Rx (OTC)

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 Substances that supplement the diet by
increasing the total dietary intake
 not intended to treat, diagnose, prevent, or
cure diseases
 It could be vitamin; mineral; herb or other
botanical; amino acid
 Can be in various form such as tablets, capsules,
softgels, gelcaps, powders, and liquids

Protein supplements for Vitamins or herbal

athletics supplements 23
Examples of dietary supplements

Protein supplements for

athletics
Vitamins or herbal supplements

lozenges, oral gel etc. that helps to Pills or tea drinks for dietary fibres
relief certain health problems
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Substances that become part of a food product
when added during the processing or production of
that food.
– Intentional food additives are added to foods to
produce a desired effect, such as to maintain
freshness, improve nutritional quality, assist in
processing or preparing food, or make a food more
appealing.

Xylitol from birch tree

Bark/ corn, a sugar
substitute

Food coloring
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 Breakfast cereals with 100% of RDA
vitamins and minerals or additional fiber
 Juice with mineral supplementation
 Yogurts and drinks with active bacterial
cultures
 Traditional foods with newly discovered
health benefits
 Foods with cholesterol modifying agents
 Foods derived from enrichment of animal
feedstock
 Genetically modified foods that have
enriched nutrients

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Example of functional food
CELSIUS (US and HK)
A carbonated drink that
contains epigallo-
catechin gallate (EGCG)
and ginger extract that
claim can burn calories.

OLLY (US and Canada) Pact (US)

Gummy that contains Snacks that contains
multi-vitamins that probiotics, fruits and
claims having nuts, omega-3, vitamins
different functions that claims having
e.g improve sleep, different functions
relief stress

ACTIVIA (global)
Yogurt that contains live
bifidus bacteria that claim to
help your digestive system
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 A food - which is formulated to be consumed or
administered enterally - under the supervision of
a physician - and which is intended for the
specific management of a disease or condition for
which distinctive nutritional requirements, based
on scientific principles are established by medical
evaluation.

trumacro
Lumega Z Mineral salts for metabolic
Vision specific medicinal food disorder patient
that contains carotenoid 28
 A common mistake made by those not
completely familiar with medical foods (MF) is to
confuse them with dietary supplements, because
both types of products have nutritional
ingredients. Medical Foods and Dietary
Supplements are not interchangeable.

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 IND (Investigational New Drug) submission to
USFDA
 Host plant biology
 Host plant processed material assayed for
◦ toxins, anti-nutrients, and allergens known to
be produced by the plant species and whether
it is known to accumulate heavy metals
 Environmental impact safety
◦ harvesting plant; control of seed stocks and
harvested material; control of waste material,
special controls for cross and microbial
contamination
 Batch-to-batch consistency and conformity
 Same QA/QC procedures as new molecular quality
entities

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 Dietary Functional Medical Botanical
Supplement Food Food Drug
Intended
Population
Healthy Healthy Diseased Diseased

GRAS As Approved
Safety General
Standard
GRAS Human
Expectation NOT GRAS
Clinical

Structure Dietary Specific

Claims Reduce Risk Disease Proven
Function Management Indications
Scientific Recognized Standard
Requirements
None None
Science Process
MD (not ND)
Supervision
No No Yes (Rx) Yes (Rx)

Specific Orphan Drug Fed. FD&C

Governing Act
DSHEA None
Act Act

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 Dong Quai - Angelica sinensis, commonly known
as "dong quai“ (當歸) or "female ginseng" - a
herb from the family Apiaceae, indigenous to
China
 widely used in TCM for gynecological ailments,
fatigue, mild anemia and high blood pressure,
used by many females for relieving pain, bloating
cramps during menstruation.
 The plant's phytochemicals consist of coumarins,
phytosterols, polysaccharides, ferulate, and
flavonoids
 It has antioxidant activity

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 It had been used heartburn, intestinal gas
(flatulence), loss of appetite (anorexia), arthritis,
circulation problems, "runny nose" (respiratory
catarrh), nervousness, plague, and trouble
sleeping (insomnia) or treating premature
ejaculation in western countries as supplement

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 What is a drug?
 Is it a food?
 Is it a dietary supplement?
 Is it a food additive?
 Why does it matter?

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intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of
disease in man or other animals
and articles other than food intended to affect
the structure or any function of the body of
man or other animals

Usually prescribed by medical doctors or with

medical advice and the drug had to be
monitored by the governing body (registered)

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 Claims for drugs must be supported by
solid laboratory and clinical data.
 Drug safety of the product, the
therapeutic claims and the quality of
ingredients must be pre-approved by the
FDA through extensive clinical testing.
 Drug candidates must first be tested in
animals before any human clinical trials
 All drugs are under physician’s supervision
 After approval, can make disease claims
and drug claims

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 Artemisia annua and Artemisinin
 Illicium verum (star anise) and Tamiflu (for
treating flu)

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 Steps to be taken before a compound is used as
drug
 Steps of the drug approval process

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IND Investigation New Drug
NDA New Drug Application

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Although well studied, many extracts exhibit
conflicting clinical results:

• Insufficient dosage (to cut costs)

• Low bioavailability
• Claims are based on borrowed data
• Poor design of clinical trials

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 Active or Not?
 What would you like to know from a TCM doctor
about the formula?
 What would you like to know from a western
doctor about the prescription?
 Would you ask the TCM pharmacist any questions
about the ingredients?

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