HERBAL MEDICINE

CHALLENGES IN CLINICAL PRACTICE

Ngatidjan

Department of Pharmacology and Therapy

Faculty of Medicine Universitas Gadjah Mada
Ngatidjan HERBMED CHALLENGES 2012 1
 THERAPEUTICAL PROCESS
Anamnesis

Physical / Clinical Examination

Clinical Diagnosis

Laboratory Examination

Diagnosis

Therapy

Ngatidjan
FailHERBMED CHALLENGES 2012
Sucess
2
 RATIONAL DRUG USE
 Prompt diagnosis
(Physiological and pathological state, genetics and biological variation)

 Prompt dugs  for every patient  individual

(Drug class, dose, preparation, administration and the possibility of
drug –drug interaction and interaction with other substances)

 Patient compliance
(attention to the disease, social - education, availability of medicine etc.)
Ngatidjan HERBMED CHALLENGES 2012 3
DRUG FOR THERAPY
 Effective and efficacious
 evidence based (from various studies  screening)

 Safe for patients

[lack of undesired effect (ADR)]
 evidence based  from various studies  screening

 Consistence (pharmacodynamics and kinetics)

 show consistency profiles in various patients, etc.

 Available  in the market

 consistent in production
Ngatidjan
and distribution, cheap, etc
HERBMED CHALLENGES 2012 4
DRUG FOR THERAPY

 evidence based
evidences that the drug is :
* safe
* effective and efficacious

 based on scientific studies

Ngatidjan HERBMED CHALLENGES 2012 5
 HERBAL MEDICINE

Ngatidjan HERBMED CHALLENGES 2012 6

HERBAL MEDICINE NOWDAYS

• Many-many preclinical studies have been done

– pharmacological studies
– toxicological studies
– pharmaceutical studies

• Few clinical studies have been done

– phase 1, 2 (mostly) and phase 3 (few)‫‏‬clinical trials

• Postmarketing surveillance?
– phase 4 clinical study (drug safety study)
Ngatidjan HERBMED CHALLENGES 2012 7
 Ginseng
Ngatidjan HERBMED CHALLENGES 2012 8
 Foeniculum vulgare
Ngatidjan HERBMED CHALLENGES 2012 9
Ngatidjan Sonchus avensis
HERBMED CHALLENGES 2012 10
 Morinda citrifolia Linn
Ngatidjan HERBMED CHALLENGES 2012 11
Ngatidjan
Morinda citrifolia L – pace
HERBMED CHALLENGES 2012 12
Ngatidjan Morinda citrifolia L – pace
HERBMED CHALLENGES 2012 13
Musa balbisiana Colla
Ngatidjan HERBMED CHALLENGES 2012 14
 rats are randomized
(amylum, cimetidine AESB or EAPK)

acclimatized 7 days pretreatment

at the day of 8 are fasted  acetosal 150 mg/kgBW

leave 5 hours, animal are sacrificed

stomach is excised  observe the ulcer  score

Negative control
Cimetidine
Musa balbisiana Colla
 unbuffered mucosal

oxygen

buffered serosal

carbogen

organbath
water 37oC

Thermostat and circulator

STUDY ON ISOLATED RAT STOMACH : GASTRIC ACID SECRETION
Ngatidjan HERBMED CHALLENGES 2012 19
 The increase of H+ concentration after histamine
130
120 UbM
110
Bj I
The increase of H+ (% of those in t0)

100
90
Bj II
80
70 Bj III
60
50 DB I
40
DB II
30
20 DB III
10
0 SMTD
-10
DMSO
-20
10
Ngatidjan 20 30 40 50
HERBMED60 70 2012
CHALLENGES 80 time (minutes) 20
 Eurycoma longifolia Jack
Ngatidjan HERBMED CHALLENGES 2012 21
 Some conventional drugs
are produced from herbal plants

Ngatidjan HERBMED CHALLENGES 2012 22

PIONEER HERB FOR MODERN DRUGS

 Ephedrine (from Ephedra)

 Cocaine (from Eythroxylon coca)  procaine etc.
 Morphine (from Papaver somniferum)  methadone etc.
 Reserpine (from Rauwolfia serpentina)  othe sympatholytics
 Quinine (from Peruvian tree)  quinidine etc.
 Atropine (from Atropa beladona)  other antimuscarinics
 Curare (from Chondrodendron tomentosum)  muscle relaxants
 Etc.
Ngatidjan HERBMED CHALLENGES 2012 23
Atropin  from Atropa beladona

Atropa beladona
Ngatidjan HERBMED CHALLENGES 2012 24
Digoxin from Digitalis purpura

Morphine, codeine, papaverine

 Papaver somniferum
Ngatidjan HERBMED CHALLENGES 2012 25
 Curare

Chondrodendron tomentosum

Ngatidjan
Strychnos toxifera
HERBMED CHALLENGES 2012 26
 DRUG DEVELOPENT (SCREENING)

Drug candidate

Preclinical study
pharmacological, pharmaceutical and toxicological study

Clinical study
phase 1, 2 and 3

Mass production and market activity

Post marketing surveillance

(phase 4 clinical study)
Ngatidjan HERBMED CHALLENGES 2012 27
 DRUG DEVELOPMENT

clinical production
drug preclinical study (market) postmarketing
candidate study surveillance
(trial) and usage

Ngatidjan HERBMED CHALLENGES 2012 28

 HERBAL MEDICINE

Ngatidjan HERBMED CHALLENGES 2012 29

HERBAL MEDICINE NOWDAYS

Evidence (for effectivity, efficacy and safety)?

 Huge early pharmacologival studies were done
 Some early toxicological studies were done
 Many pharmaceutical studies were performed
 Few clinical studies were done (phase 1, 2, 3)
 Very limited post marketing surveillance.
 What are the problems
Ngatidjan HERBMED CHALLENGES 2012
? 30
 HERBAL MEDICINE CHALENGES
 The quantity and quality of safety and efficacy data
needed of herbal medicine are far from sufficient
 Inadequate research methodology for herbal
medicine  unconclusive or may misleading.
 Inadequate experties involvement in every step of
drug development.
 Standard methodology for herbal medicine clinical
trial were not acceped  unclonclusive.
(Chaudhury, 2005)
Ngatidjan HERBMED CHALLENGES 2012 31
 Problem solving
for herbal medicine

Ngatidjan HERBMED CHALLENGES 2012 32

HERBAL MEDICINE CHALENGES

 Preclinical studies
 Systematic – programmed studies has to be done
 focuse on priority based drug / herb  conclusive.

 Improve research facilities (equipments for chemical

and biomedical experiments, animals house, etc.)

 Stimulate expert involvement – knowledge and skill

improvement.
Ngatidjan HERBMED CHALLENGES 2012 33
HERBAL MEDICINE CHALENGES
 Clinical studies – Clinical Trial
 Prioritized – programmed clinical trial has to be done
 focused based on priority  conclusive.
 Standard clinical trial protocol has to be applied
depend on the step of clinical trial (phase 1, 2, 3)
according to GCP and GCLP.
 Expert (clinical specialist) involvements have to be
encouraged .
Ngatidjan HERBMED CHALLENGES 2012 34
HERBAL MEDICINE CHALENGES
 Other aspects
 Cultivation – programmed planting according to good
plant production  stadardized medicinal plant.
 Good harvesment and post harvestment methods
 quality of raw material of herbal medicine
 Good manufacturing practice (GMP) in production (in
every step of production)?

Ngatidjan
 standardized product (herbal medicine)
HERBMED CHALLENGES 2012 35
Ngatidjan HERBMED CHALLENGES 2012 36
INTEGRATED PROGRAMMES

 Academic (university)
(including hospital and other research institution)

 Business – industry (including trade institution)

(apply research products to serve public need)

 Goverments
(regulate, synchronize and harmonize activities)
Ngatidjan HERBMED CHALLENGES 2012 39
Thanks for the attention