Extraction of Natural Products
What is common among the following? - It all comes
from plants
Natural Products, Secondary Metabolites = medicinal
properties
Range of products from natural products
 25% of drugs in use today are derived from
natural products
 61% of the 877 drugs introduced between 1981
and 2002 can be traced to a natural product
origin (J. Nat. Prod. (2003) 66:1022)
 In certain therapeutic areas, the impact is even
higher, e.g., anti-cancer (74%) and anti-bacterial
(78%)
 Natural product to become a medicine it takes
10 to 15 years from pre-clinical to clinical trial
Where do we get the natural products in plants?
PRIMARY METABOLISM
Primary metabolism comprises the chemical processes
that every plant must carry out every day in order to
survive and reproduce.
Primary metabolites: (product of primary metabolism)
 Photosynthesis
 Glycolysis
 Citric Acid Cycle
 Synthesis of amino acids
 Transamination
 Synthesis of proteins and enzymes
 Synthesis of coenzymes
 Synthesis of structural materials
 Duplication of genetic material
 Reproduction of cells (growth)
 Absorption of nutrients
Natural products and Ecology
Examples: lipids, steroids, alkaloids, fatty acids (most
are non-polar)
Plants – produce natural products as a toxin, attraction,
anti pest and fungal, phenomes.
SECONDARY METABOLISM
Secondary metabolites:
Not all plants produce the same secondary metabolites
Unique product of a particular plant
I. Anthraquinone Glycosides – most of agents are
used as laxatives and purgatives
 Mechanism: the glycosides are absorbed from the
small intestine and re-excreted in the large intestine
where they increase the motility to produce
laxation.
 Aglycons produce gripping effect so it is
recommended to prescribe antispasmodic with
them.
II. Cardiac Glycosides - These compounds are found in
various medicinal plants and have strong direct
action on the heart. Foxglove
 Cardiac glycosides such as digitoxin, digoxin, and
convallotoxin support heart strength and rates of
contraction when failing.
 These compounds also have a diuretic effect that
stimulates urine production and aids in removal of
fluid from tissues and the circulatory system.
 Cardiac glycosides also improve circulation, lower
blood pressure and relieve the urinary tract.
 Caution: plants containing cardiac glycosides are
often poisonous.
III. Coumarins – it offers widely divergent
strengthening mechanisms that include sunscreen
protection, blood thinning and muscle relaxant
action.
 Found in many plants, popular examples include the
tonka bean (Dipteryxodorata) and members of the
Umbelliferae and Solanaceaefamilies.
 Madre de cacao
IV. Cyanogenic glycosides – These glycosides are based
upon cyanide, a very deadly poison, but in small
doses, they can serve as a muscle relaxant. Can be
used to suppress and soothe dry coughs.
V. Flavonoids - are found widely throughout the plant
world and they have a wide range of medicinal uses
and actions.
 Flavonoids are antioxidants known as polyphenols
which improve circulation and relieve tissues
damaged by pathogens.
 They often act as pigments giving a yellow or white
color to flowers and fruits.
 Some flavonoids have anti-viral and anti-
inflammatory properties.
VI. Phenols - are plant compounds that are thought to
be produced to protect against infection and
herbivory by insects.
 They are often anti-inflammatory and antiseptic and
can have anti-viral properties.
 Phenols vary in structure and range from salicylic
acid (similar to aspirin) to complex sugar-containing
phenolic acids. Wintergreen and willow contain
salicylates.
 Members of the mint family often contain phenols.
VII. Saponins - This group of active compounds obtains
its name from the fact that like soap, they produce
lather when placed in water.
 There are two main forms of saponins: steroidal and
triterpenoid:
 Steroidal saponins are very similar to the chemical
structures of many of the human body’s hormones
including estrogen and cortisol, Examples plants
containing saponins include agave, wild yam, and
several members of the lily family. Several native
plants are used in a process to produce synthetic
hormones for humans.
VIII. Tannins - Most plants produce tannins. Serve as a
deterrent to herbivory by insects and grazing
animals given that that they provide a harsh
unpalatable flavor.
 Tannins are also useful in curing leather because of
their tendency to contract and astringe tissues by
binding with precipitating proteins.
 Familiar to wine drinkers as the ingredient that
causes headaches.
 Used to `tan` leather, tannins cause tissue to
contract.
 Sources include beer, wine, chocolate and citrus
foods.
IX. Volatile oils - are extracted from plants and are used
to produce essential oils that play a very important
role in medicinal botany.
 These oils are often very complex and can be
comprised of 100 or more compounds.
 Volatile oils are the component of plants that offer
the strong aroma to attract foraging wildlife.
 Volatile oils are strongly antiseptic and normally
have anti-inflammatory properties as well.
 Aromatherapy involves the use of volatile
(essential) oils to alter moods and perception as
well as to detoxify the body.
The study of natural products is multidisciplinary!
Some milestones in natural products chemistry:
 Morphine, Strychnine, Quinine, Camphor, Cocaine,
Coniine, Ephedrin, Cholesterol, Salicin,
Ginsengoside Rs2, Brevetoxin-A, Taxol, Dynemicin
A, Damacenone, Cis-jasmone, Menthol
Process of Natural Product Extraction, Isolation and
Identification
HERBAL DRUGS PREPARATION
Decoction
 Solutions of the water soluble constituents of plant
drugs prepared by boiling the drug with water.
 For extraction of drugs with water soluble and non-
volatile constituents, and drugs of hard and woody
nature.
 TIPS: Should be freshly prepared.
 A decoction is considered by herbalists to be the
most effective method for delivering herbs into the
body to treat a problem.
 In Chinese medicine the word decoction is "tang,"
which means soup.
 You can use wood, leaves, and stems
 Ratio: 1:4 plant part: water
Preparation
 Previously sliced drug barks or wood is boiled with
water in a vessel of enameled iron or earthenware
for a definite length of time (15min.)
Examples
 Psydium guajava(“bayabas”)
 Used as an antibiotic
 Most Philippine herbal preparations are by
decoctions
Infusion
 Crude drugs of light structure without dense tissues
and containing water-soluble constituents.
 The drug maybe freshly broken, thinly sliced, cut
small, or coarsely powdered in order to facilitate
the solvent penetration.
 Water (cold or hot)
 Examples: Tea
Tincture
 A tincture is an extraction of herbal ingredients
using a solvent.
 Solvents can be water, oil, glycerin, vinegar or
alcohol.
 For most dry plant matter it is effective to use 80
proof alcohol such as vodka or rum.
 The usual ratio of herb to solvent is determined by
weight and is 1:5 or one part herb to five parts
alcohol.
Syrups
 Equivalent to decoction plus sugar
What if I want to extract the natural product?
General isolation strategy of natural products:
Drying
Increase surface area
Solvent extraction – like dissolves like
Solvents:
 Polar solvents - water
 Non-polar solvents – ethanol, methanol,
cyclohexane, benzene
 Acids
 Bases
“Like dissolves like” Thermodynamically spontaneous
process
Separate the solute from the solution – use water bath
or rotary evaporator
Crude extract – powdery substance, all the non-polar
substances from your plant. You can use it in soaps,
ointments, and lotions.
What if I want to extract and identify the actual
secondary metabolite?
General isolation strategy of natural products:
1. Fractionation - use acids
2. Simple chromatography – use spectrometer
Issues and challenges in Natural Products today
1. Loss of biodiversity
2. Intellectual Property Rights
 Patent protection (pharmacompanies)
 Biopiracy(source countries)
3. Western drugs:
 High cost of drug development
 New drug leads and targets
4. Herbal products:
 Regulation
 Improvement in quality
 Elucidation of mechanism of action
Research areas in natural products today ETHNOBOTANICAL RESEARCH
1. Structural elucidation(speed of analysis, sample Importance of the environment:
throughput complexity of structures) I. Food
2. Metabolonomics  More than 90% of the calories consumed by people
3. Synergy and biotransformation worldwide come from 80 plant species
4. Biosynthesis  Fruits, nuts, mushrooms, honey, spices and other
5. Biological activity foods that human and wildlife consume originate
 Ecological from natural ecosystems.
 Pharmaceutical properties / drug discovery  Fish comprises 10% of man’s protein intake.
 Healthcare and cosmetic products  In 1989 the total world fishery catch reached an
6. Molecular biology and Biotechnology astounding 100 million metric tons (since then
7. Quantitative natural products chemistry annual landings have dropped or at best remained
the same)
TESTING NATURAL PRODUCTS II. Medicines
Antibacterial testing – mix the extract with the medium  About 80% of the world’s population still use plants
as their primary source of medicine.
 Close to 30% of all pharmaceuticals on the market
today were developed from plants and animals.
III. Fuel, timber, Fiber and other resources
 Most houses, furniture and even many clothes are
made from natural products, including wood, oils,
resins, waxes, gums and fibers.
 The cocoons of silk worms are the basis of the
valuable, centuries-old Asian silk-making industry.
IV. Air and water purification (ecosystem service)
Zone of inhibition - indicates the degree of sensitivity of  Forests purify our air and our water by taking in
bacteria to a drug. carbon dioxide, regulating water vapor, releasing
Toxicity settings oxygen, and cycling nutrients.
Cell culture - refers to the removal of cells from an V. Climate modification
animal or plant and their subsequent growth in a  Water cycle – by transpiration
favorable artificial environment. VI. Drought, erosion, and flood control
Normal cell lines  It recedes the chances of drought, erosion, and
 They were spontaneously immortalized.(e.g.: flood
Cardio-myocytesfrom rat) VII. Economic value
•Immortalized  Examples: native products, tourist spots (boracay)
 Transfectedwith some sort of oncogene; SV40 VIII. Social/cultural value
(Simian virus)Large T antigen  Environment has a direct link to our culture and
 (T IDBL) language
 Tumorcells (e.g.: Human cervix carcinomas: HeLa) Philippine Biodiversity
 Hybridomas  105 species of AMPHIBIANS…
Chorioallantoic membrane assay (CAM ASSAY) …82 species are FOUND ONLY in the
 Test for Angiogenic Agents Philippines
 To produce anti-tumor drug  More than 254 species of Reptiles …
with 208 sp. endemic to the Philippines
 Uses chicken and duck egg, angiogenesis =
formation of new blood vessels  We have more than 576 species of birds
200 of these occur only in the Philippines.
 Of the 179 species of land mammals,
111 species are found only in the Philippines
 Around 20,940 species of insects
69.8% are endemics 2. We are in the inside of the bracket of the
 15,000 species, 50% are endemics world coral reef and rain forest. Tropical
70 – 80% Flowering plants country
 INLAND WATERS… 211 Lakes, 18 major rivers, 22
marshes, swamps and reservoir
Phil. Wetlands = 1616 species of aquatic plants 3675
species of fauna
 Mangroves - 37 tree species in the world
34 tree species occur in the Philippines
 Corals - 462 coral species recorded* (an additional
 30 species can be expected)
At least 21 undescribed species recently found in the
Calamianes Islands, Palawan. 12 species are endemic to
the Philippines & Indonesia. 1 new species of Leptoseris
in the Kalayaan Is.
 Fish - about 4,000 species in the Indo-Pacific region 3. Different elevation, climate, and rainfall
2,177 recorded species in the Philippines (Herre,1953)
 1,300 species coral reef and reef-associated species
225 deep sea species
75 open sea – pelagic species
385 estuarine and coastal non-reef associated species
170 freshwater species
 Molluscs - 22,000 freshwater, land and marine
species
 Nine species of Giant Clams worldwide
Seven of these occur in Philippine waters

Cavite’s Own Treasure

• Mts. Palay-palay - Mataas na Gulod Protected
Landscape
• Ternate, Maragondon & Nasugbu
• FAUNA 1. Luzon cloud rat, Sierra Madre shrew mouse,
• 176 species, 137 genera and 5 classes golden crowned flying fox, pygmy fruit bat,
o – 83 species of birds brown deer, whiskered Pitta- LUZON
o – 19 species of frogs and 9 genera 2. spotted deer, warty pig, white throated
o – 24 species of insects jungle flycatcher, Negros bleeding heart- W
o – 32 species of reptiles VISAYAS
o – 18 species of mammalia 3. tamaraw, tree frog, scarlet collared flower
• FLORA pecker, Mindoro Tarictic- MINDORO
• – 127 families, 719 species, and 453 genera 4. Tarsier, Sulu woodpecker, blue-winged
o • 45 species of ferns, 21 genera and 10 racquet tail MINDANAO, SULU, BOHOL & E
families VISAYAS
o • 25 families of tree species and 10 are 5. peacock pheasant, bear cat, otters, mouse
important timber species deer, flying squirrel, Philippine cockatoo-
• Impatiens caviteana – endemic to mt. palay-palay PALAWAN
• FUNGI Disappearing Biodiversity
• - 15 genera of soil actinomycetes • Coral Reefs of the World
Phil Coral reef - 5% in excellent condition lowest in
Why is the Philippines so rich? (in biodiversity) SEAsia!!!. 4.86%, 30,000km2
1. Geological history 617,000 square km or 1/6 of ONE percent of the marine
environment (which is 75% of earth)
• Status of Philippine Mangroves
1918 The Philippines had an estimated 450,000
hectares of mangroves (Brown and Fisher, 1920)
1990 139,725 hectares (31.05%)
1993 138,000 hectares (30.67%)
1995 only 117,000 hectares (26%) remain
(DENR, 1995) now 17% remain
The loss is largely attributed to the conversion of
mangroves to fishponds
Other factors include reclamation for residential,
commercial & industrial purposes and excessive
harvesting of trees for fuel
Less than 6% of the country’s Original forest remains!
Total number of wildlife species in the Philippines and the Indian and those of the Orient (China,
Major No. of Endemic Threatene Japan, Tibet,…etc).
Taxa Species Species d
• Medical information transferred by:
Species
Amphibians 101+ 82+ (78%) 24 • ORAL from generation to generation (In tropical
Reptiles 258+ 170+ (66%) 8
Africa, North & South America and Pacific countries)
Birds 576+* 195+ (34%) 74
Mammals 204+** 111+ (54%) 51 • WRITING (e.g. the Egyptian Papyrus Ebers c. 1600
Total 1139+ 558+ 50%) 157
BC)
• Found in Egypt in the 1870s, the Ebers Papyrus
contains prescriptions written in hieroglyphics for
over seven hundred remedies.

Pharmacognosy
• An applied science that deals with the biological,
biochemical and economic features of natural crude
drugs and their constituents.
• It is a study of drugs from plant and their natural
derivatives.
• E.g.: Digitalis leaf & its glycosides (digitoxin)
Rauwolfia root & its alkaloids (reserpine)

Threats to Philippine biodiversity Monographs - on a large number of crude drugs,

• Human pollution giving written descriptions, tests of identity, purity
• Invasive species and assays of active constituents:
• Illegal animal trade Pharmacopoeia – collection of different
• Illegal logging monographs
• Deforestation • British Herbal Pharmacopoeia
• Bleaching of corals • American Herbal Pharmacopoeia.
• Dynamite fishing • Chinese Herbal Pharmacopoeia (Materia medica)
• Mining
• Soil erosion and landslide Classification of medicinal plants:
• Industrial pollution I. Alphabetical:
• Aquaculture Either Latin or Vernacular names maybe used.
• Mobile pollution Limitation: Although they are simple and suitable for
• Domestic pollution quick references, It gives no indication of
interrelationships between drugs e.g. Pharmacopoeias.
What solutions can we offer as scientist? II. Taxonomic:
1. Helping in the management of these resources! Based on botanical classification, drugs are arranged
BY PROVIDING FACTUAL BASIS – RESEARCH according to the plants from which they are obtained,
2. Biodiversity profile, plant preservation into:
3. Surveying techniques: Classes, orders, families, genera and species.
Any viable form of collecting or sampling. Need to be III. Morphological:
sited at a level appropriate to the question • Drugs are divided into groups such as : leaves,
Examples: flowers, fruits, seeds, herbs and entire organisms,
• ◦Point-Quarter wood, barks, rhizomes & roots (known as organized
Proximity to a central point within a cross drugs).
• ◦Quadrant • Dried lattices, extracts, gums, resins, oils, fats and
Sampling within a small area waxes (known as unorganized drugs).
• ◦Pitfall traps IV. Pharmacological or therapeutic:
• ◦Mist netting This involves the grouping of drugs according to the
4. Determining Dominance and Carbon Stocks pharmacological action of their most important
5. Water quality test constituents or their therapeutic uses, e.g cardiotonic
6. Soil testing drugs.
V. Chemical or Biogenetic:
Acc. To the important constituents e.g. alkaloids,
Pharmacognosy The response of some drugs in glycosides, volatile oils, etc.., OR based on their
powdered form or in their smooth section surface to biosynthetic pathways.
the UV , e.g. in detecting of adulteration of genuine of
rhubarb from rhapontic rhubarb (blue fluroscence) Official and unofficial drugs:
Introduction: • OFFICIAL DRUG is one that is listed and described as
• Plants have universal role in the treatment of being a definite therapeutic agent in the
diseases in the major systems of medicine. pharmacopoeia.
• In Mesopotamia and Egypt, Unani-Islamic, and • UNOFFICIAL DRUG is that one that are not
Ayruvedic (Hindu) systems centered in Western Asia recognized in the pharmacopoeia and is used as
therapeutic agent.
The species name is usually chosen to indicate certain
characteristics of the plant:
1. Striking characteristic of the plant:
• Cassia acutifolia (sharp pointed leaflets)
• Conium maculatum (maculate = spotted)
2. Characteristic color:
 Piper nigrum (black)
 Digitalis purpurea (purple)
3. An aromatic plant (certain aroma)
 Myristica fragrans (nice aroma)
 Caryophyllus aromaticus (refers to aroma)
4. D-Geographical source:
 Cinnamoum zeylanicum ( growing in Ceylon)
 Hydrastis canadensis (growing in Canada)
5. Pharmacological activity:
 Papaver sominferum (inducing sleep)
 Lytta vesicatoriam (causing blistering)
6. General meaning:
 Allium sativum (cultivated)
 Riticum vulgare (wild).
The generic name may indicate certain characters of the
plant:
e.g. Atropa means fate who cuts the thread of life
Glycyrrhiza means gluco = sweet, riza = root,
Linum, Linea = thread)
Production of herbal drugs:
Collection, drying and storage of drugs:
The preparation of each drug for the market depends
on its morphological nature, constituents, geographical
source and other factors.
A. Collection of Crude Drugs:
1. Effect of Time of the Year (Seasonal var.):
It has been found that active constituents in plants vary
in amount and nature throughout the year.
- Rhubarb is collected in summer (anthranol in
winter→anthraquinones in summer).
- Colchicum corm: collected in spring (alkaloids).
Hyoscyamous muticus collected in summer (alkaloids).
2. Time of the Day
- Digitalis is collected in the afternoon.
- Solanaceous leaves collected in the morning.
- Salix collected at night.
3. Stage of maturity and age:
- Clove: collected in bud form.
- Santonica fl & tea leaves: in as unexpanded flower
buds.
- Solanaceous leaves: at flowering stage.
- Pyrethrum flower: in fully expanded.
4. General factors:
- Flowers are collected in dry weather.
- Leaves are collected when plant is flowering.
- Fruits and seeds when fully mature but unripe.
- Underground organs when aerial parts die down.
- Barks in spring (when they are easily separated).
- Unorganized drugs in dry weather (not rainy).
B. Drying of Crude Drugs
Reasons of Drying:
- To decrease size and weight (facilitate packing,
transport and storage).
- Facilitate powdering.
- Prevent enzyme action, microbial growth and
degradation of active constituents.
Enzyme action
Desirable: e.g. Vanilla pods, required slow drying.
Undesirable: e.g. Digitalis leaves, required fast drying.
Methods of drying:
1. Drying in open air: in sun and under cover sheds at
night or during wet weather, e.g. clove, cinnamon,...
2. Artificial oven drying (Oven-drying is more rapid than
air- drying, controlled temp. and more suitable for use
in the wet weather countries. Leaves, herbs & flowers:
20-40oC, barks & roots: 40-65oC.
3. Vacuum drying: in oven, rapid and at low temp.
4. Lyophilization used for biological fluids, enzymes,
proteins and royal jelly.
C. Storage of Crude Drugs:
During storage, Drugs are affected by light, moisture,
temp., air oxygen (physicochemical) and by fungi,
bacteria, worms, insects and mites (biological)
Long storage is not recommended, due to deterioration.
Therefore, drugs should be stored in sealed containers
in cool dark places.
Evaluation of Crude Drugs
Means to identify and to determine quality, safety and
purity.
1. It has to be certain of identity of the collected plant
from proper source by matching to authentic plant
sample
3. Preparation by proper cleaning, drying and garbling.
4. Proper preservation of cleaned, dried, pure drug
against contamination.
Evaluation of drugs involves the following methods:
1. Organoleptic
2. Microscopic
3. Chemical
4. Physical
Organoleptic evaluation:
Organoleptic refers to evaluation by means of the
organs of sense which includes:
- The macroscopic appearance of the drug,
- Its odour and taste and the feel of the drug to the
touch.
Description of the macroscopic characteristics of a drug
include:
Shape and size.
Colour and external markings
Fracture and internal colour.
Odour and taste.
Microscopic evaluation:
The microscope is essential in the identification of
powdered drug and in the detection of the adulterants
in powdered plant OR animal drugs. Microscopical
description of the drug in sectional view and powdered
form is listed in official monograp .
Histology refers to the character & arrangement of the introduced into a living organism has the effect of
tissues in a drug. altering body functions.
Some drugs have no cellular structure (gums, resin). These alterations may prove useful in the treatment of
Some are composed of microscopic units, such as disease (therapeutic application) or it may cause
diatoms (kieselguhr) or hairs (Lupulin, kamala). disease (toxicity).
Histological studies on very thin transverse (TS) or BFAD now DFA
longitudinal (LS) sections properly mounted in suitable
stains, reagents or mounting media. 3 major aspects of Pharmacology
In the powdered drugs the cells are mostly broken, Pharmacy
except those with lignified walls, but the cell contents  Pharmaceutical sciences
(starch, calcium oxalate, aleurone grains …etc) are  Study on drug making
scattered in the powder and become very evident in the Pharmacology
mounted specimen.  Study on drug disposition and action
Microscope can be used for a quantitative Toxicology
microanalysis of admixed or adulterated powders. This  Study on poison and drug toxicity
study is done by counting a specific histological feature
(stomatal index, palisade ratio) in a measured quantity Sub-discipline of pharmacology:
of the unknown powder and comparing the count with I. General or Basic Pharmacology
that obtained for the same feature in a known standard Basic principles
sample. II. Systemic Pharmacology
Study of drug groups based on body systems
Chemical evaluation III. Regulatory Pharmacology
Chemical tests are employed to identify crude plant Drug regulations and Laws
drugs. IV. Pharmacognosy
E.g. characteristic red colour developed in Study of sources of drugs
Cascara on addition of NH3 test solution. V. Pharmacotherapeutics
To ascertain the purity of certain drugs Focus on using drugs to treat diseases
E.g. to detect the presence of inorg. iodine in thyroid VI. Molecular Pharmacology
tablets by adding a starch test solution. Study of pharmacology at molecular level
Chemical assays are dependent on the pharm. VII. Clinical Pharmacology
extractive processes with subsequent purification of the Study of pharmacology in patients
main constituent. VIII. Metrology
In many drugs the chemical assays represents the only the science of measurement
method of determining the official potency. IX. Posology
Study on drug dosage
Physical evaluation: X. Pharmacokinetics
Typical physical constants is very rare. Study on drug movement in the body
In jalap and clove, the specific gravity should be higher XI. Pharmacodynamics
than that of water. Study on drug action in the body
The elasticity of certain fibers, such as cotton, is a XII. Pharmacogenetics
physical constant of importance. Study on genetic factors
Alkaloids aconitine (light blue), berberine (yellow), XIII. Comparative Pharmacology
emetine (orange). Comparative study in different species
Alkaloid quinine has blue fluroscence in acid solution in
UV or even in daylight. Sources of drugs:
The use of physical constants on active constituents.:
Solubility, specific gravity, optical rotation, melting Natural sources – primary and secondary metabolites
point… etc. Chromatoigraphic  Carbohydrates
 Glycosides (sugar + aglycone)
What is pharmacology  Lipids
Greek words of Pharmacology  Proteins
pharmakon - drug or poison  Alkaloids
Logos - study of
 Volatile oils
The science that deals with
 Plant exudates
the fate of drugs in the body, what does the body do to
 Antibiotics, Hormones, Growth factors,
the drug - (pharmacokinetics)
Cytokines, Vitamins, Toxins
their actions on the bod, what does the drug do to the
body - (pharmacodynamics)
Synthetic sources
 Natural mimicking
A drug is
any substances differ from a normal constituent of the  Natural modification
body or one that is required for normal bodily function  Laboratory synthetics
(e.g. food, water, oxygen) that when applied to or
Route of administration - the path by which a drug is
taken into the body
Classification
 Topical route
Applied onto the skin or
mucous membrane
 Enteral route
Given into GI tract
Desired effect is systemic
 Parenteral route
Usually involve injection
Desired effect is systemic
Drug nomenclature
 Chemical name
Desired effect  Non-proprietary or Generic name
 Local effet o Approved name
Usually by topical route Name not yet in Pharmacopoeias
 Systemic effect o Official name
Usually by enteral and Drug name in Pharmacopoeias
parenteral Aspirin (U.S.P.), Aspirin (B.P.)
o Common name
Usually the same as generic name
 Proprietary or Trade or Brand name
Examples: Rimadyl and Zeniquin

Topical route Local Systemic Drug classification

effect effect
 Classifications based on Origin
Epicutaneous /
o Natural preparations or Galenicals
Transdermal / o Pure compounds
Transmucosal / o Semi-synthetic substances
Nasal / o Purely synthetic compounds
Inhalational / /  Classifications based on Use
Eye drops / o Classify drugs according to the organ
Ear drops / system upon which they exert their most
Intravaginal / prominent actions
Intramammary / o Anesthetic drugs
Enteral route Local Systemic o Anti-convulsants
effect effect o CNS stimulants
Oral / o ANS drugs
Sublingual / o Cardiovascular drugs
Buccal / o Anti-hypertensive agents
Rectal / o Diuretics
Parenteral Local Systemic o Muscle relaxants
route effect effect o Analgesics
Subcutaneous / o Anti-inflammatory drugs
Intramuscular / o Antihistamine
Intravenous /
Intraarterial / Evaluation of New Drugs (Drug development)
Intraosseous / Objectives – Effective and safe
Intraperitoneal / Testing in 2 aspects
Intrathecal / 1. Pharmacological profile - To see if it is effective
Pharmacopoeias 2. Toxicological profile - To see if it is not harmful
 a book containing directions for the identification of
samples and the preparation of compound I. Screening Test
medicines, and published by the authority of a  Thousands of chemicals are screened in
government or a medical or pharmaceutical society laboratory
 a reference work for pharmaceutical drug  Most tests are focused on Pharmacological
specifications profile
 United States Pharmacopoeias (U.S.P.)  Very few chemicals may passed as potential
 National Formulary (N.F.) candidates
II. Pre-clinical Test
 New and Non-official Drugs (N.N.D)
Medical Pharmacology Textbooks  This step involves mostly with testing in
laboratory animals
 Goodman and Gilman's the Pharmacological Basis
of Therapeutics, 12th ed.  Testing
o Pharmacological tests
 Principles of Medical Pharmacology
 Pharmacy
To find a suitable preparations Nutrition: diets, organic food, natural products, health
 Pharmacokinetics supplements
To find the right dosage Exercise: gym, sports
 Pharmacodynamics Stress management: spa, massage
To understand the mechanism of action Middle class/ upper class phenomenon
o Toxicological tests
 Acute toxicity test – which dose would be lethal, Health supplements:
fast effect  contains one or more, or a combination of the ff:
 Subacute toxicity test (a) Vitamins, minerals, amino acids, fatty acids,
 Subchronic toxicity test enzymes, probiotics and other bioactive substances.
 Chronic toxicity test – will not ill, but the (b) Substances derived from natural sources,
exposure to the drug is longer including animal, mineral and botanical materials in
 Reproductive toxicity test the forms of extracts, isolates, concentrates,
 Carcinogenicity test metabolites.
 Genotoxicity test  In practice, many of so-called dietary supplements,
 Teratogenic effect = effect on the offspring or the like, contain or consist of botanical materials
III. Clinical Test derived from traditional medicine
This step will be done in targeted populations
 Phase I Popularity of herbs and non-mainstream medical
Study in normal people modalities worldwide:
 Phase II  From nature: perceived to be safe
Study in small group of sick people  Inadequacy of mainstream medicine
 Phase III  Heavy promotions and word of mouth
Study in large group of sick people
 Phase IV Herbs as source of mainstream medicine
Post-marketing evaluation Active ingredients identified
Philippine Medicinal Plants Evidence of safety and efficacy
Terms: More than 40% of modern medicine armamentarium
I. Mainstream medicine Medicine Plant source Folkloric Modern use
 Medicine as practiced by holders of degree of use
medicine, nursing, PT, etc Atropine Atropa To dilate Anticholiner
 Synonyms: conventional, standard, regular, belladonna eyes gic
orthodox, western, allopathic Hyoscya Hyoscyamus Sedative Anticholiner
 Practice based on evidence mine niger gic
Tubocura Chondrodendro Arrow Skeletal
II. Complementary medicine
rine n tomentosum poison muscle
 Group of diverse medical and health care
relaxant
systems, practices and products which are not
Physostig Physostigma Ordeal Anticholinest
part of mainstream medicine
mine venenosum poison erase
 Vs traditional medicine
 Vs indigenous medicine Pilocarpi Pilocarpus Poison Parasympath
 Vs Oriental medicine ne jaborandi omimetic
 Complementary medicine is used along with Morphin Papaver Sedative, Analgesic
mainstream medicine e somniferum analgesic
Codeine Papaver Sedative, Antitussive,
III. Alternative medicine somniferum analgesic analgesic
 Alternative medicine is used in place of Philippine scenario: No approved therapeutic claims
mainstream medicine  Memory Plus
 Sleapasil
IV. Traditional medicine  Optein
V. Indigenous medicine  Liveraide
 Lungcare
VI. Integrative medicine  Kidneycare
 A total approach to care that involves the  Kolestrim
patient’s body, mind, and spirit  Diabetrol
 Combines mainstream medicine with CAM  Robust, Fitrum
practices that have shown the most promise or Herbs that harm
is beneficial or effective a) Kavakava
b) Aristolochia
Tendencies/trends: For weight reduction
People take more active participation in their health Nephropathy [interstitial fibrosis]
care/ wellness Aristolochic acid
Use withdrawn in the Philippines
 c) Mahuang  Paradigm: mainstream vs integrative
Ephedra  Physician-patient relation
For weight reduction: high doses  Placebo role
Stroke Rational use of herbal medicines considers the criteria
d) Comfrey of high quality, effectiveness, safety, affordability, and
Panacea suitability to the patient.
Hepatotoxic
Pyrrolizidine RCTs as gold standard for efficacy: By this standard,
Not recommended for systemic use considered effective are:
e) Ginkgo Garlic for short-term use in dyslipidemia (1 to 3 months
f) Kava Piper methysticum use)
Some evidence: maybe beneficial for anxiety Ginger for nausea and vomiting of pregnancy
Risk of liver damage
How do we conduct scientific study?
Assessing herbs: Parts used and constituents
BASED ON STRENGTH OF EVIDENCE Parts used: mature leaves
 Randomized controlled trial [RCT] Constituents:
 Non-randomized RCT Terpenes - cineol, limonene, camphor, borneol,
 Cohort study sesquiterpenes, monoterpenes, triterpenes
 Case-control study Alkaloids
 Epidemiological study Flavonoids
 Case report Saponins, tannins
 Expert opinion Could be commercial source of camphor
 Anecdotal report Safety studies
Toxicity:
Sizing up Philippine herbs Acute toxicity: ld 50 = 143.6 g/kg
 Vigorous research in the 30s to 50s Subchronic toxicity
 Darak as source of tikitiki Safety studies
 1970s:Community-based health programs Mutagenicity:
 SLK: sampalok, luya, kalamansi syrup for cough Rec assay
Ames test
 BLS: bawang, luya, sili liniment for rheumatism
Micronucleus test
 ABK: abukado, bayabas, kaymito decoction for
Host-mediated assay
diarrhea
All negative findings
 Makabuhay ointment for scabies
Even exhibited anti-mutagenic potential vs mitomycin d,
 Akapulko ointment for fungal infect
dimethylnitrosoamine and tetracycline
NIRPROMP: National Integrated Research Program on
INITIAL CLINICAL STUDIES
Medicinal Plants
For cough
 Akapulko - for skin fungal infection Side effect: diuresis
 Bayabas - as antiseptic SUBSEQUENT CLINICAL STUDIES
 Niyogniyogan - for ascariasis For kidney stone
 Lagundi - for cough
 Sambong - for urinary stones, diuretic Chemolytic effect of sambong: in vitro (Rico study)
 Yerba Buena - as analgesic, pain OBJECTIVE
 Tsaang gubat - as antispasmodic, coic TO DETERMINE THE EFFECT OF SAMBONG ON CALCIUM
 Bawang - to lower cholesterol STONE IN VITRO
 Ulasimang bato - to lower uric acid Rico F. Sambong (Blumea balsamifera): its effect on
 Ampalaya - to lower blood sugar calcium stone. Philippine Journal of Urology 1992; 2: 9-
13
Use of herbs in the context of integrative medicine STONE DISSOLUTION
 As a total approach to care that involves the Was greatest for sambong given at 40 mg/kg
patient’s body, mind, and spirit
 Combines mainstream medicine with CAM Ranking of studies in the assessment of evidence FDA
practices that have shown the most promise or 2005
is beneficial or effective  Randomized, controlled clinical trials
Household level  Cohort studies [longitudinal]
 Herbs and other remedies that are  Case-control studies
 Safe to use  Cross-sectional studies
 Beneficialfor trivial ailments  Uncontrolled case series or cohort studies
 Accessible  Time-series studies
 Accepted  Ecological studies [cross-population
Clinic level  Descriptive epidemiology
  Case reports

Take note:
 Use supplements only where needed:
 For deficiency: Vitamin A, iron, iodine,
 Where indicated: folic acid + iron calcium +
Vitamin D, pyridoxine, zinc
 Eat right.
 Exercise.
 Get enough sleep.
 Practice hygiene.
 Manage stress.
 Do not smoke.
 Feed your soul.