Clinical study of plant derived medicine

CLINICAL STUDY OF PLANT
DERIVED MEDICINE
Guidance by – Dr. A.U. Tatiya Sir .
Presented by –Vishvanath N. Vaidya .
DEPARTMENT OF PHARMACOGNOSY,RCPIPER ,
SHIRPUR.

 Introduction
Types of clinical Trial
 Types of Phases used in Clinical trial
 Protocol for clinical trial in Herbal medicines
 Examples of plant derived medicines
 Limitations of Herbal drugs in clinical trials
 CONTNTS

 A type of research study that tests how well new medical approaches
work in people.
 These studies test new methods of screening, prevention, diagnosis,
or treatment of a disease. Also called clinical trial.
 A clinical trial is a prospective biomedical or behavioral research
study of human subjects that is designed to answer specific
questions about biomedical or behavioral interventions (vaccines,
drugs, treatments, devices, or new ways of using known drugs,
treatments, or devices).
 INTRODUCTION

Clinical trials can be classified in to :
1. Treatment trials
2. Screening trials
3. Prevention trials
4. Supportive care trials
TYPES OF CLINICAL TRIALS

1. Treatment trials :
It refers to trials
which involves test on
new treatments, new
combinations of
drugs, or new
approaches to surgery
or radiation therapy.
2. Screening trials :
It refers to trials which test
the best way to detect certain
diseases or health conditions.
3. Prevention trials :
These are those trials which
intend to find better ways to
prevent disease in people who
never had the disease or to prevent
a disease from returning .These
approaches may include vaccines,
minerals,vitamins,medicines etc.
4.Supportive care
trials :
Explore
ways to improve
comfort and the
quality of life for
individuals with
a chronic illness.

 TYPES OF CLINICA TRIALS
Phase 1
• Phase 2
Phase 3
• phase4

 THE EFFICIENCY AND EFFECTIVENESS AND COST OF A
CLINICAL TRIAL DEPEND ON:
response to each treatment
influence of other factors such as age, gender or life style
number of patients
 how patients are selected for the trial
how patients are allocated to treatments
 type of trial: parallel or crossover
 compliance of patients to treatments
 how data are recorded, analysed and interpreted

 RISKS
There are risks to clinical trials.
•There may be unpleasant, serious or even life-threatening side effects to
experimental treatment.
•The experimental treatment may not be effective for the participant.
SIDE EFFECTS AND ADVERSE REACTIONS :
•Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or
other physical problems.
•Experimental treatments must be evaluated for both immediate and long-term side
effects.
•Side effects are any undesired actions or effects of the experimental drug or
treatment.

 THE CRITICAL PATH OF CLINICAL TRIAL
Planning
Protocol . CRF
Regulatory and
Ethical Approval
Trial Documents .
Materials
Select
investigators Initial Visits
Site
Assessments
Patient
Recruitment
Periodic
Monitoring
Study Termination
Data Data Statistical Final
entry clean-up analysis Report
• START • END
GCP. IND
11

REGULATORY REQUIREMENTS FOR THE CONDUCT OF
CLINICAL TRIALS ON HERBAL MEDICINES-
• Traditional medicines are governed by the Drugs and Cosmetics Act of 1940 and
the Drugs and Cosmetics Rules of 1945.
• In 1959, the Government of India amended the Drugs and Cosmetics Act to
include drugs which are derived from traditional Indian medicine.
• In 1993, the guidelines for the safety and efficacy of herbal medicines
developed by an expert committee.
• No new herbal medicines other than those authorized by the licensing
authorities be allowed to be manufactured or marketed, except for those
mentioned in ancient scriptures.

 Plants remain an important source of new drugs, new drug leads and
new chemical entities.
 The plant based drug discovery resulted mainly in the development of
anticancer and anti-infectious agents and continues to contribute to the
new leads in clinical trials.
 For many centuries plants have been the main source of crude drugs
used to cure or alleviate human sickness.
 In today’s era of medicine engineering also, plants play an equally
important role in drug discovery and development.
PLANT-DERIVED NATURAL
PRODUCTS IN CLINICAL TRIALS

Sr . No Parameter Garlic
1 Synonym Garlic ,allium
2 Botanical source bulbs of plant known as Allium sativum.
Family : Liliaceae.
3 Chemical constituents •29 % carbohydrate
•56 % of proteins
•0.1 % of fat
•mucilage
•0.06 to 0.1 % of volatile oil
•Volatile oil of the drug is the chief constituent
and contains allyl propyl
1.GARLIC

CLINICAL STUDIES OF GARLIC EXTRACTS :
 Powdered garlic preparations tested in clinical studies include Kwai, Pure Gar as
well as unbranded or generic dried garlic.
 Kwai is manufactured by Lichtwer Pharma AG in Germany and distributed in the
United states by Litchwer Pharma US.
 The tablets contain a preparation known as LI 111 that is standardized to
contain 600 mcg allicin in 100 mg garlic powder.
 Garlic preparation studied clinically for reduction in risk for atherosclerosis heart
disease include dried garlic, aged garlic , garlic oil , and raw garlic.
 The end points of those trials include elevated serum cholesterol, hypertension ,
blood clotting factors and lipid oxidation.
 most number of studies has been conducted on the ability of dried garlic
essentially Kwai , to reduce elevated levels of plasma lipids , especially
cholesterol.

PREPARATION OF GARLIC EXTRACT :
•Garlic extract is prepared by storing sliced garlic in 15 to 20 % aqueous ethanol for 18
to 20 months.
•After this , the liquid is filtered and concentrated.
•Most of the sulphur compounds responsible for the characteristic garlic odor are
removed during processing.
• few allicin or alliin derived compounds obtained. The sulphur compound measured
for quality purposes is S – allylcycteine.
•Garlic extract is available in both liquid as well as dry forms.
•The liquid form contains 10 % ethanol.
•The trials were much higher than those suggested in available product.

Sr . No. Parameters Information
1 Manufacturer : Lichtwer Pharma AG , company
2 US distributer : Lichtwer Pharma U.S.
3 Botanical
ingredient :
Garlic clove powder
4 Extract name : LI 111
5 Quantity : 100 mg concentrated dry garlic, equivalent to
300 mg fresh garlic.
6 Processing : Garlic cloves are cut in to slices and carefully
dried in 50 – 60 ̊c air for several hours. The
dried slices are ground in to powder and sieved.
7 Standardization : 600 mcg alliicin per tablet
8 Formulation : Tablet
9 Level of evidence : I
10 Therapeutic benefit Yes

 TRIAL DESIGN : PARALLEL
Detail Type
Study duration 4 months
Dose 4 tablets daily (800 mg garlic powder)
Route of administration Oral
Randomized Yes
Randomized adequate Yes
Blinding Double blind
Placebo Yes
Drug comparison No
Site description 30 general practices
No. of subjects enrolled 261
No. of subjects completed 219
Sex Male and Female
Age 4 7- 71 years (mean 59)
1 8

 CRITERIA :
Inclusion criteria:
 Total serum cholesterol values of 200 to 300 mg / dl and triglyceride values
of 200 to 300 mg / dl
 End points :
 Total cholesterol and triglyceride levels , as well as supine and diastolic blood
pressure , were measured.
 Results :
 After four months ,mean cholesterol levels dropped in the garlic group by 12
% (266 to 235 mg /dl) and triglyceride levels by 17 % (226 to 188 mg / dl).
 The difference between the garlic and placebo was highly significant.
 analysis showed that patient with initial total cholesterol levels between
250 to 300 mg / dl showed the most improvement compared with placebo.

Side effects :
Mild garlic smell in 2 percent of garlic and 9 % of placebo groups.
Also minor gastrointestinal upset.
Recommended dose:
Take two tablets three times daily with liquid ,ideally with meals.
Cholesterol lowering results observed after 1 weeks of usage.
Caution :
If a disease or health related condition requires the lowering of cholesterol , consult
a doctor.

Uses :
1. As carminative, aphrodisiac , expectorant, stimulant and
disinfectant in the treatment of pulmonary condition.
2. It is highly used as condiment.
3. Oil of garlic is used as anthelmintic and rubefacient .
4. Allicin is antibacterial.
5. Garlic oil is used in high blood pressure and atherosclerosis
.
6. Fresh garlic is prophylactic against amoebic dysentery.

Sr . No Parameter Ginger
1 Synonym Zingiber , Zingiberis
2 Botanical source Rhizomes of Zingiber officinale
Zingiberaceae
3 Chemical constituents Volatile oil (1 – 4 %)
Starch (40 – 60 %)
Fat (10 %)
Fibre (5 %)
Inorganic material (6 %)
 GINGER

Sr . No. Parameters Information
1 Manufacturer : Dalidar Pharma Ltd. Israel
2 Botanical
ingredient :
Ginger root
3 Extract name : Zintona
4 Quantity : 250 mg
5 Processing : Dried root powder
6 Standardization : pungent phenolic compounds
7 Formulation :
capsule
Formulation : capsule
8 Indication : Motion sickness
9 Level of evidence : II
10 Therapeutic benefit
:
yes
 Zintona-Produt profile

A. Several studies used generic preparations of powdered ginger root and
rhizome.
B. Most studies described the product as powdered ginger and gave the
dose.
C. None of the studies mentioned profiling the ginger for quantities of
gingerols.
D. Ginger products have been tested in clinical studies of effectiveness in
reducing nausea and vomoting due to administration of
chemotherapy,emergence from general anesthesia.
E. Morning sickness associated with pregnancy and most commonly for
motion sickness , vertigo, nausea, vomiting ,cold sweat.
F. Here Zintona was studied clinically and three studies with Zintona
demonstrated a benefit for this ginger product on motion sickness.

TRIAL DESIGN : PARALLEL
Subjects received one of the seven substances frequently used to
prevent seasickness and matching placebo of another substance in a
double method.
Nobody received only placebo.
The comparison medications were Touristil (cinnarazine 20
mg,domperidone 15 mg ),marzine (cyclizine 50 mg ),Dramamine
(dimenhydrinate 50 mg , caffeine 50 mg ).
In most cases, subjects took the medication two hours prior to
departure.
For Touristil and Zintona an additional dose was administered four
hours later.

Type Details
Study duration 1 day
Dose 500 mg 2 hours prior to departure and after 4
hours
Randomized Yes
Randomized adequate Yes
Blinding Double blind
Placebo No
Drug comparison Yes
Drug name Touristil, Marzine, Dramamine, Peremesin,
stugeron, Scopoderm TTS
Site description Ship
No. of subjects completed 1475
Sex Male and Female
Age 16 – 65 years

 CRITERIA :
 INCLUSION CRITERIA :
•Tourists participating in a whale watching tour in Norway between the ages of 16
and 65 years old.
 EXCLUSION CRITERIA :
•Pregnant or nursing women, persons who had used antiemetic or anti allergic
drugs within the past 48 hours, patients with glaucoma and persons with a history
of adverse reactions to any of the substances to be tested.
 End points :
•The outcome measures were vomiting ,malaise and subjective reports of adverse
events.
•The information was collected via a questionnaire gathered at the end of the trip.

 Results :
1. Questionnaires were completed by 85.5 percent of volunteers(n =
1489)
2. Those who tried to avoid seasickness by fixing their eyes on the
horizon, by putting cotton in their ears, or by wearing a “ sea band ”
on the wrist were excluded from analysis.
3. None of the study medications offered complete protection from
seasickness.
4. All had similar rates of efficacy compared to an earlier trip without
prophylaxis when 80 % got sick.
5. No statistical difference was seen between treatments.
6. In each treatment group 4.1 to 10.2 percent experienced vomiting
and 16.4 to 23.5 percent experienced malaise .

 SIDE EFFECTS :
•No serious adverse reactions reported.
•Sleepiness and tiredness were reported generally for all seven agents.
 Dose :
•For motion sickness : adults and children over six years
•0.5 g, 2 – 4 times daily
•1 g ginger 30 to 60 minutes before travel
 CAUTION :
•WHO suggests that it is not recommended for children less than six years of age.
•USP suggests that patients with an increased risk of hemorrhage or those taking
anticoagulants should use ginger with caution.

 USES:
A. Used as stomachic, an aromatic, a carminative, stimulant
and flavouring agent.
B. Ginger oil is used in mouth washes, ginger beverages and
liquors.
C. Ginger powder is effective in motion sickness.
D. It ha s been suggested that adsorbent, aromatic and
carminative properties of ginger on GI tract cause
adsorption of toxins and acid enhanced gastric motility.
E. These may have probably blocking effects of GI reactions
and nausea.

•Green tea is derived from Camellia sinensis
•Family : Theaceae
 Chemical constitutes:
•A cup of green tea usually contains 300 to 400 mg polyphenols
•.
•Polyphenols are a large class of mildly acidic compounds with anti
oxidant properties.
GREEN TEA

•Polyphenols can be divided in to many subclasses, including
catechins , an example of which is epigallocatechin gallate.
 PREPARATION OF GREEN TEA:
•Heating the freshly picked leaves shortly after harvesting
process produces green tea.
•This process inactivates the enzymes.

Sr. No Parameter Information
1 Manufacturer: Thomas J. Lipton Co., North America
2 Botanical ingredient : Green tea leaf extract
3 Processing : Lyophilized (Freeze dried) tea solids
4 Indication: Cardiovascular risk factor
5 Level of indication : III
 LIPTON RESEARCH BLEND
 CLINICAL STUDY OF GREEN TEA
PRODUCTS
TRIAL DESIGN:
Parallel
After a two week pretrial period in which all subjects consumed 900 ml (6 cups )
of water per day, they were divided in to three groups and given 900 ml (6 cups) of either
water, green tea, black tea (0.5 g black tea extract per cup) daily.

Type Duration
Study duration 1 month
Dose 6 (0.5 g tea extract in 150 ml) cups daily
Randomized No
Randomized adequate No
Placebo No
Drug comparison No
Site description Single center
Sex Male and female
Age 20 – 61 groups
 TRIAL DESIGN

CRITERIA:
Inclusion criteria:
Ages 18 to 65 years, healthy, non smoking,not using vitamin C, vitamin E,
carotenoid, selenium,or zinc supplements or consuming a medically or weight
loss diet, and a stable weight for atleast one month before the start of the day.
Exclusion criteria :
Pragnant or lactating women.
END POINTS :
Blood samples were obtained before and after experiments period.
Serum lipid concentrations, plasma and low density lipoprotein (LDL) antioxidant
status,resistance of LDL to oxidation and plasma malodialdehyde and LDL – hydro
peroxide concentration were measured.

RESULTS :
•Consumption of green tea or black tea did not affect serum lipid
concentrations, resistance of LDL to oxidation ex vivo,or markers of oxidative
damage to lipids in vivo.
•However ,consumption of green tea slightly increased total antioxidant
activity of plasma .
SIDE EFFECTS:
 Not mentioned.
•Daily consumption of 900 ml green tea per day for four weeks had no
effect on serum lipid concentrations or resistance of LDL to oxidation ex
vivo.
•Future research should focus on mechanisms by which tea flavonoids
may reduce the risk of cardiovascular disease other than by increasing
the intrinsic antioxidant status of LDL.

HEALTHY WEIGHT LOSS BENEFITS OF GREEN TEA
A. Healthy diet weight loss can be significantly aided by the use of green tea
extract.
B. Research confirms that the active ingredients of green tea promote increase in
metabolic rate and burning of fat.
C. There are many varieties of green tea available and all of them are greatly
beneficial.
D. A study that appeared in American Journal of Clinical Nutrition found that 4%
increase in overall energy expenditure in 24 hours was attributed to green tea
extract.
E. The findings further specified that the extra expenditure took place during the
day and concluded that the 4% increase due to green tea extract actually
translated into thirty five to 43% increase in daytime thermo genesis. (Thermo
genesis is the body’s rate of burning calories.)

GINSENG
oBiological source : Dried roots of various
species of Panax , like
P.ginseng(Koreanginseng)
P. japonica
(Japaneseginseng)
P. notoginseng
(Chineseginseng)
P. quinquefolium
(American ginseng)
oFamily : Araliaceae

 CHEMICAL CONSTITUTES :
•Contains a mixture of several saponin glycosides, belonging to
triterpenoids group.
They are grouped as follows :
•Ginsenosides
•Panaxosides
•Chikusetsusaponin
•Ginsenosides contain aglycone dammarol while panaxosides have
oleanolic acid as aglycone.
•Panaxosides give oleanolic acid, Panaxadiol and panaxatriol on
decomposition.

The root of Ginseng is mainly used in the traditional medicine.
Commercially supplied roots are graded according to their source, age, part of root,
and the method of preparation.
The root can be used fresh, or prepared as white ginseng (peeled and dried) or red
ginseng (steamed and dried).
The fresh root is often sliced thinly and taken with or without honey, or it can be
boiled in soup.
White or red ginseng can be powdered, extracted, or made in to a tea.
The trials reviewed in test ginseng for its effects on physical performance,well
being, cognitive performance, the immune system, and diabetes.
It indicates that the use of ginseng may reduce the risk of cancer.

Sr. No. Parameters Information
1 Manufacturer : Pharmaton S.A ., Switzerland
2 Botanical ingredient : Ginseng root extract
3 Extract name : G 115
4 Quantity : 100 mg extract (equivalent to 500 mg
root)
5 Processing : no information
6 Standardization : 4 % ginsenosides
7 Formulation : Capsule
8 Indication : Physical performance in healthy athletes
9 Therapeutic benefits : Yes
 PRODUCT PROFILE : GINSANA

Type Detail
Study duration 9 weeks
Dose 2 (100 mg G 115)capsules daily
Randomized Yes
Randomized adequate No
Bliding Double blind
Placebo Yes
Drug comparison No
Site description Not described
No.of subjects completed 28
Sex Male
Age 21 – 29 years
Trial design : parallel

CRITERIA :
 Inclusion criteria :
Healthy male athletes whose training program consisted of at least ten hours per
week with their trainer.
End points :
Performance capacity was measured before treatment, at the end of 9 weeks, and 1,
3, 7 and 11 weeks following the treatment.
Oxygen uptake was measured at rest and during exercise with a cyclic ergometer.
Pulmonary functions and heart rate were monitored, as well as reaction times to
visual signals.

RESULTS :
Following 9 weeks, the ginsana group had an increase in maximum oxygen
uptake of 17 % and a lowering of the maximum exercise heart rate by 10 %.
The oxygen pulse, oxygen uptake divided by heart rate, increased by 26 %.
Serum lactate levels decreased by 40 %.
There was an increase in parameters of pulmonary function, i.e. forced
expiratory one second volume and forced vital capacity, as well as a shortning of
reaction time to visual stimuli.
These changes persisted for three weeks following treatment.

DOSE :
Two capsules with water in the morning or one capsule in the morning and one
in the afternoon.
Optimal results have been shown with four weeks continuous use, when taken
as directed.
PRECAUTION :
Diabetic patients should consult a physician to taking ginseng root, since it may
slightly reduce blood glucose levels.

 USES :
An important immunomodulatory drug.
Increases the natural resistance and enhances the power to overcome the illness
or exhaustion.
Has both stimulant and sedative properties.
Used as aphrodisiac, demulcent and in gastritis and anemia.
Useful in adrenal and thyroid dysfunctioning.
Used for curing the giddiness and prolonging life of elderly and diabetic persons.

1. Barrett Marilyn , Ph D Editor, The Handbook of Clinically Tested
Herbal Remedies , Vol II,CBS publishers and Distributors, New
Delhi, India, page No. – 787, 789, 796, 799 -802, 1175,1197,4.93-
508,673-691,403-429.
2. Tripathi KD , Essentials of MEDICL PHARMACOLOLOGY , Seventh
Edition, Jaypee Brothers Medical Publishers PVT . Ltd. New Delhi
,Page No.-073-81
3. Kokate, C .K. Purohit, A .P. Gokhale, S .B.2010.PHARMACOGNOSY,
forty fifth edition, Nirali Prakashan,Pune ,Page No.-1.103,1.156.11
4. www.wikipedia .net
5. www.Gogle images .com
REFERENCES

Clinical study of plant derived medicine

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