The basis of the rational development of Phytotherapy · The basis of the rational development...

The basis of the rational development

Symposium20 Years

Cologne (Germany), 18th June 2009

UNIVERSITAT DE BARCELONA

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Unitat de Farmacologia i Farmacognòsia - Facultat de Farmàcia - S. Cañigueral

rational development of Phytotherapy

Prof. Dr. Salvador CañigueralUnitat de Farmacologia i FarmacognòsiaFacultat de FarmàciaBarcelona


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Rational development of Phytotherapy

The appropriate use of herbal products in therapy and health care

Aimed to:Aimed to:


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products in therapy and health care

©Salvado

rCañ

igue

ral

Foeniculum vulgare

How to use appropriately

herbal products in health

care and therapy?


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care and therapy?

Natural does not mean safe

Rational Phytotherapy

P r

e m

i s

e s

There is a scientific evidence supportingthe efficacy of many herbal remedies for

Appropriate use of herbal remedies in therapy


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P r

e m

i s

e s

the efficacy of many herbal remedies for

certain indications

The efficacy will only be achieved with the

correct use of the herbal medicines.

Evidence based products

What is required?


Appropriate use of herbal remedies in therapy


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products

Information

Education

What is required?


Quality

Requirements to meet


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Efficacy

Safety

Herbal Medicinal Products(HMP)

Quality

Quality is the basis forHMP


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Quality is the basis for

the reproducibility of

safety and efficacy.

Eff

ica

cy

Sa

fety

Quality(Based on Bauer, 1998)

Plant used in traditional medicine

Th

e d

ev

elo

pm

en

t o

f n

ew

m

ed

icin

es

fro

m p

lan

tsDiscovery of an interesting

pharmacological activity or an

interesting clinical effect

Chemical research

Extracts

Quality control

development

Other plants


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Th

e d

ev

elo

pm

en

t o

f n

ew

m

ed

icin

es

fro

m p

lan

ts

Marketed medicine

Marketing authorisation

Preclinical pharmacology

and toxicology studies

Clinical trialsGalenic

development

Extractsand

bioactivemolecules

Production of plant

material

Complexity of herbal drugs and herbal drug preparations

Inert substances (matrix)


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Adjuvant substances

Active principlesPotential

antagonists

Potentially allergenicor toxic

substances

1. Thymol

2. Carvacrol

3. Linalool

Chemotypes in the oil from Thymus vulgaris

Variability of the herbal material


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3. Linalool

4. Geraniol

5. Eucalyptol

6. α-Terpineol

7. trans-Thujan-4-ol / Terpinen-4-ol

Profile by GC:

Thymol 36,0 - 55,0 %

Carvacrol 1,0 - 4,0 %

p-Cymene 15,0 - 28,0 %

OH

OH

Thyme esential oil Thymi aetheroleum



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p-Cymene 15,0 - 28,0 %

γ-Terpinene 5,0 - 10,0 %

Linalool 4,0 - 6,5 %

ß-Mircene 1,0 - 3,0 %

Terpinen-4-ol 0,2 - 2,5 %

European Pharmacopoeia, 2008

Carvacrol

OH

γ-Terpinene

OH

Terpinen-4-ol

p-CymeneThymol

Linalool ß-Myrcene

During the vegetative cicle


0,6

0,8

1

1,2

1,4

Serp

en

tin

e (

%)

in r

oo

ts


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Evolution of the content of serpentine in the roots of Catharanthus roseus

0

0,2

0,4

0,6

0 1 2 3 4 5 6 7 8 9

Age of the plants (months)

Serp

en

tin

e (

%)

in r

oo

ts

Species Urtica dioica L., U. urens L.

Active principles

¿?

Indication Symptomatic treatment of mictu-

rition disorders in benign prosta-

Influence of the extraction

Extracts of nettle root


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rition disorders in benign prosta-

te hyperplasia (BPH) at stages II

and III according to Vahlensieck

Dose Drug: 4-6 g/day (infusion); dry

extracts (MeOH 20%, EtOH

70%): 300-600 mg/day; fluid

extract (EtOH 45%): 4.5-7.5 ml;

tinture (40% EtOH): 15 ml; etc…

ExtractInhibition of

prostate grow (%)

p vs.

Control

Cyclohexane -23.5 0.040

Extracts of nettle root

Influence of the extraction


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Ethyl acetate 5.0 1.000

n-Butanol 1.3 0.916

Methanol 20% 51.3 0.003

Water 26.5 0.267

Suramine 25.7 0.156

Effect of nettle root

extracts (U. dioica) on

experimentally indu-

ced prostate hyper-

plasia in mouse

(Adapted from Lichius and Muth, 1997).

Quality issues related to herbal products

� Complexity of the composition of herbal drugs and

herbal preparations

� Variability of the biological materials (biodiversity,

chemotypes, etc.).

� Influence of the collection and post-harvesting processes (drying, storage, etc)


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processes (drying, storage, etc)

� Influence of the extraction process

� The active principles are sometimes not identified or only partially known

� Possible contaminations (adulterations, heavy

metals, pesticides, microbial, etc.)

Stability of herbal medicinal products

Tea tree oil (Melaleuca alternifolia)

Formed by

oxidation of

terpinen-4-olOH

OH


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16Terpinen-4-ol(≥ 30%)

Harkenthal et al., Pharmazie 55: 153-154 (2000)

OH

1,2,4-Trihydro-xymenthane

Responsible of

contact dermatitis

caused by aged

oxidized oils

OH

Identity Quantitative determi-

nation of active prin-

Quality control of herbal drugs and herbal preparations

Objectives


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nation of active prin-

ciples and markersPurity

Contaminants Stability

http://www.edqm.eu

European Directorate for the Quality of Medicines (EDQM) Council of Europe

2007

Members: 37

European Pharmacopoeia


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Members: 37

�36 European states

�European Union

Observers: 20

�19 European and

non European states

�WHO

Analytical methods and specifications for

medicinal products


Working groups

Working groups on herbal drugs and herbal drug

preparations (2008)

Permanent groups

13A Phytochemistry

Groups ad hoc

MQH Microbiological quality of


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Unitat de Farmacologia i Farmacognòsia - Facultat de Farmàcia

13A Phytochemistry

13B Phytochemistry

13H Fatty oils and

derivatives

MQH Microbiological quality of

herbal drugs and herbal

drug preparations

PST Pesticide residues

TCM TCM herbal drugs

WXT Water for extraction

194

233251

160

180

200

220

240

260

Nu

mb

er

of

mo

no

gra

ph

s


Monographs of herbal drugs and herbal drug preparations


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67

125

0

20

40

60

80

100

120

140

160

Nu

mb

er

of

mo

no

gra

ph

s

2nd 3rd 4th 5th *6th

-1996Year: 1997-2001 2002-2004 2005-2007 2008-2009

*) Including supplements 6.1 to 6.4

Edition:

Soy isoflavons are obtained from the seeds of Glycine max (= G. soja)

OHO

Glycosides of

Soy isoflavones and menopause


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Soy beans

O

OHOH

Genistein

O

O

OH

HO

Daidzein

Isoflavones are phytoestrogens

� They bind the estrogenic receptors (ER).

� Higher affinity for ERβ than for ERα.

� Higher transcriptional activity on ERβ than on



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� Higher transcriptional activity on ERβ than on

ERα.

� Preferential activity on CNS, bone and vascular wall.

� Genistein has the higher affinity for ER.

Clinical interest in menopause


� Menopause symptoms,

mainly hot flushes.

� Reduction of the post-


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� Reduction of the post-

menopause vascular

risk.

� Reduction of the risk of

ostheoporosis.


Why the clinical trials are contradictory?

Menopause 2006; 13 (5): 831-839


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Williamson-Hughes

et a

l.Menopause 2006; 13 (5): 831

Genistein <10 mg/day Genistein >15 mg/day

The European market of Phytotherapy

Prescription of herbal medicinal products by medical doctors

9%

9%

7%

41%

Austria

Poland

Italy

Europe Prescription quota(in percentage)


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Source: IMS International 2002

73%

43%

38%

18%

18%

13%

9%

0% 20% 40% 60% 80% 100%

France

UK

Germany

Hungary

Belgium

Spain

Austria

Self-medication Prescription



Appropiate use of herbal remedies in Therapy


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products

Information

Education

Good and reliable information tools for health professionals

Information and education



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Solid education oportunities forhealth professionals.

�Books

�Journals

� Internet




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� Internet

�Pregraduate education

�Postgraduate and continued education

�Education for the general population

�Congresses, symposia, workshops

Books

Phytotherapy: information and education


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Phytotherapy: Journals

Revista de Fitoterapia


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Phytotherapy: Journals


2009: 10 years

“New look”

The journal of the Phyto-therapy Societies of:


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therapy Societies of:

�Spain

�Chile

�Mexico

�Portugal

� Electronic version of the


� Phytotherapy data base

Phytotherapy: Internet

www.fitoterapia.net


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� Vade mecum of herbal

products in Spain

� Activity alerts

� Book reviews

� Links

�Books

� Journals

� Internet




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� Internet

�Pregraduate education

�Postgraduate and continued education

�Education for the general population

�Congresses, symposia, workshops

IL3 (University of Barcelona)

Master on Phytotherapy (2 years)

Phytotherapy

Postgraduate education: distance learning


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Postgraduate courses on:

• Fundamentals on Phytotherapy: quality, safety

and efficacy (1 year)

• Clinical Phytotherapy (1 year)

Universidad de Barcelona

Universidad Autónoma de Barcelona

Colegio de Farmacéuticos de Barcelona

Phytotherapy

Postgraduate education: presential learning


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Master on Medicinal Plants and Phytotherapy (2 years)

Postgraduate Diploma on Medicinal Plants and Phytotherapy

(1 year)

C O L · L E G I D E

FARM ACÈ U TICSD E LA PR O V IN C IA D E B AR CE LO N A


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Sociedad Españolade Fitoterapia


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www.fitoterapia.net/sefit/sefit.htm

Iberoamerican Council of Phytotherapy

Consejo Iberoamericano de Fitoterapia

Argentina

Brasil

Chile

C

I


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Founded in Sevilla (18th October 2007)

Chile

México

Portugal

España

I

A

F

2nd Iberoamerican Congress of Phytotherapy

Lisbon (Portugal)

8th-10th October


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8th-10th October2009

Thank you very much for your attention

Symposium20 Years

Cologne (Germany), 18th June 2009


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for your attention

The basis of the rational development of PhytotherapyProf. Dr. Salvador Cañigueral


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The basis of the rational development of Phytotherapy · The basis of the rational development...

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