Herbal Medicine

Development
 Discovery
Target identification

Area of interest in terms of drug indication?

Relevant cellular or molecular targets?

Appropriate assays–established or to be developed?

Available relevant literature?

Patent situation in the target area?

 Discovery
Resource identification
Potential resources for novel drugs: - Natural
organisms (plants, fungi, bacteria, animals)

52% of the drugs approved in the U.S. from 1981-

2002 were natural products or derived from them

26 plant based drugs were approved during 2000-

2006, including novel-molecular based drugs
 Discovery
Methods for drug discovery
Ethnobiological approach: Traditional use of
natural organisms for medicines

Published literature on traditional medicinal plant

use (e.g. documented traditional healers‘ experience)

Advantages:
- Pre-selection of potentially active resources
- Promising safety profile (age-long experience)
- Cost-efficient and comparatively fast
Natural product screening
Natural product screening
Process development in herbal medicine
Lead compounds
Identification of lead compounds
Drug targets
 Preclinical development
In vitro profiling
Biochemical assays (e.g. enzyme activity
assays)
Cell culture assays (e.g. cancer cell lines)
Isolated tissue assays (e.g. mucosa model)
In vitro toxicology
Investigate potential toxic effects
in bacteria- or cell cultures
 Preclinical development
In vivo testing - Animal model (mouse or rat)
Drug action: - Behaviour and reaction
- Physiology
- Histopathology
Toxicology test:
Acute toxicity
Subchronic toxicity
Tissue specific toxicity
Tolerability
 Preclinical development
Consider ethical aspects (e.g. number and kind of
animals used).

Objectives:
To develop the pharmacological profile
To determine the acute toxicity in at least 2
animal species
To assess toxicity with studies ranging from
2 weeks to several months
 Steps in pre-clinical test
Step One: Get an idea for a drug target.
Drugs usually act on either cellular or genetic chemicals in
the body, known as targets, which are believed to be
associated with disease.

Use a variety of techniques to identify and isolate

individual targets to learn more about their functions and
how they influence disease.

Compounds are then identified that have various interactions

with the drug targets that might be helpful in treatment of a
specific disease.
 Steps in pre-clinical test
Step Two: Develop a Bioassay

A Bioassay is a “live” system that can be

used to measure drug effect.

It may be a culture of cells or organs or a

whole animal.
 Steps in pre-clinical test
Step Three: Screen the drug in the Bioassay

This is the actual test of the drug on the chosen

bioassay.

This will determine if the drug is SAFE and if

it is EFFECTIVE in the bioassay (BEFORE
it is ever tested on humans!)
 Steps in pre-clinical test
Step four: establish what dosage amount
of the drug is SAFE and what dosage amount of the
drug is TOXIC.

Most drugs have a toxic level or an amount at

which the drug will become harmful instead of
helpful.
 Steps in pre-clinical test
Step Five: Application is made to the Food and
Drug Administration (FDA) as an Investigational
New Drug (IND).

IND must show how the drug:

Is manufactured.
Appears (color, solubility, melting point, particle
size, moisture content).
Formulated (pills, liquid, etc. + inactive ingredients).
Will be analyzed for purity, concentration, stability.
Will be tested for safety (this will be the basis for
allowing first use in humans).
Preclinical Information Required Before A Selected
Drug Candidate Can Be Administered To Humans

Pharmacological activity
Pharmacokinetics and drug metabolism
Toxicology
Pharmaceutics

Decision to proceed to man only after thorough

characterization of dose/concentration
response relationships of candidate
compound in vitro and in vivo
Summary
 Your assignment
Write a research proposal involving drug
development from herbal source:
1/ Topic, the purpose of the research
2/ Literature review
3/ Methodology: materials, procedures (plant
process, extraction, in vitro and in vivo test…)
4/ Bibliography or reference list
Submit in power point during the MIDTERM
EXAM