صفحه 1:
صفحه 2:
PHG 456
صفحه 3:
Introduction
= According to the World Health Organization (WHO), because of
poverty and lack of access to modern medicine, about 65-80 % of
the world’s population which lives in developing countries depends
essentially on plants for primary health care. Currently, the major
pharmaceutical companies have demonstrated renewed interest in
investigating higher plants as sources for new lead structures and
also for the development of standardized phytotherapeutic agents
with proved efficacy, safety and quality. Herbal medicinal
preparations are normally very popular in developing countries with
a long tradition in the use of medicinal plants and also in some
developed countries such as Germany, France, Italy and the United
States where appropriate guidelines for registration of such
medicines exist.
صفحه 4:
Definition and main characteristics of
herbal medicines (phytotherapeutic agents)
= Phytotherapeutic agents or phytomedicines are standardized herbal
preparations consisting of complex mixtures of one or more plants
which are used in most countries for the management of various
diseases. According to the WHO definition, herbal drugs contain as
active ingredients plant parts or plant materials in the crude or
processed state plus certain excipients, i.e., solvents, diluents or
preservatives. Usually, the active principles responsible for their
pharmacological action are unknown. One basic characteristic of
phytotherapeutic agents is the fact that they normally do not
possess an immediate or strong pharmacological action. For this
reason, phytotherapeutic agents are not used for emergency
treatment.
صفحه 5:
" Other characteristics of herbal medicines are their wide
therapeutic use and great acceptance by the population. In
contrast to modern medicines, herbal medicines are frequently
used to treat chronic diseases. Combinations with chemically
defined-active substances or isolated constituents are not~
considered to be herbal medicines. It is important to note that,
although homeopathic preparations may frequently contain
plants, they are also not considered to be herbal medicines.
= Conditions for which consumers use phytomedicines in
Germany, a country where herbal drugs are widely used,
include: common cold (66%), flu (38%), digestive and/or
intestinal diseases (25%), headache (25%), insomnia (25%),
stomach ulcer (34%), nervousness (21%), circulatory disorders
(15%), bronchitis (15%), skin diseases (15%), and fatigue and
exhaustion (12%). However, so far, relatively few herbal drugs
have been evaluated scientifically to prove their safety, potential
benefits and effectiveness. The sources of raw material and the
good practices of manufacturing processes are certainly the |
essential steps for the quality control of herbal medicines. |
صفحه 6:
= Phytotherapeutic agents are normally marketed as
standardized preparations in the form of liquid, solid
(powdered extract), or viscous preparations. They are
prepared by maceration, percolation or distillation (volatile
oils). Ethanol, water, or mixtures of ethanol and water are
used for the production of fluid extracts. Solid or powdered
extracts are prepared by evaporation of the solvents used in
the process of extraction of the raw material.
" Some phytotherapeutic agents are greatly concentrated in
order to improve their therapeutic efficacy. The standardized
powder extract of Ginkgo biloba (50:1), for instance, means
that 50 parts of raw material were processed to yield 1 part
of standardized powder extract. In this process, it is also
possible to remove, when necessary, some secondary
metabolites present in the plants which may produce
undesirable side effects.
صفحه 7:
= Compared with well-defined synthetic drugs, herbal medicines
exhibit some marked differences, namely:
1) the active principles are frequently unknown;
2) standardization, stability and quality control are feasible but not
easy;
3) the availability and quality of raw materials are frequently
problematic;
A) well-controlled double-blind clinical and toxicological studies to
prove their efficacy and safety are rare;
5) empirical use in folk medicine is a very important characteristic;
6) they have a wide range of therapeutic use and are suitable for
chronic treatments;
7) the occurrence of undesirable side effects seems to be less
frequent with herbal medicines, but well-controlled randomized
clinical trials have revealed that they also exist;
8) they usually cost less than synthetic drugs.
صفحه 8:
The worldwide herbal medicine market and the
main causes for the increased interest in herbal
medicines
During the past decades, public interest in natural therapies, namely
herbal medicine, has increased dramatically not only in developing
countries but mainly in industrialized countries. This has increased the
international trade in herbal medicine enormously and has attracted
most of the pharmaceutical companies, including the multinationals.
Until a few years ago, only small companies had interest in the
marketing of herbal medicines. Currently, most large multinational
companies are interested in commercializing herbal drugs.
It is estimated that the European market alone reached about $7 billion
in 1997. The German market corresponds to about 50% of the
European market, about $3.5 billion. This market is followed by France,
$1.8 billion; Italy, $700 million; the United Kingdom, $400 million;
Spain, $300 million; the Netherlands, about $100 million. European
herbal medicines are distributed under 6 basic therapeutic categories:
cardiovascular, 27.0%; respiratory, 15.3%; digestive, 14.4%; tonic,
14.4%; hypnotic/sedative, 9.3%; topical, 7.4%; others, 12.0%.
صفحه 9:
" The herbal medical database indicates that the herbal medicine
markets in Asia and Japan reach $2.3 and 2.1 billion,
respectively. However, in no other country has the herbal
medicine marketplace grown more than it has in the in USA. A
few years ago, this was a non-existent category of medicine.
The US herbal medicine market reached about $3.2 billion in
1996, and $5 billion in 1999. According to a national survey,
about 60 million Americans over 18 years of age use herbal
drugs to treat colds, burns, headaches, allergies, rashes,
depression, diarrhea and menopause, among others.
= Currently, most medicinal herbs, such as Aloe vera, Panax
quinquefolius (American ginseng), Echinacea, Alium sativum,
Ginkgo biloba, Serenoa repens (saw palmetto), Valeriana
officinalis, etc., are cultivated in the USA and exported to
Europe and the Orient. As a natural consequence, many large |
companies have introduced a line of herbal products into their |
sales.
صفحه 10:
The phytomedicine market has grown at an expressive rate worldwide
since 1985 (from 5 to 18% a year). Several important factors have
contributed to the growth of this worldwide phytotherapeutic market,
among which the following may be mentioned:
preference of consumers for natural therapies; 000000
concern regarding undesirable side effects of modern medicines and
the belief that herbal drugs are free from side effects, since millions of
people all over the world have been using herbal medicines for
thousands of years;
great interest in alternative medicines;
preference of populations for preventive medicine due to increasing
population age;
the belief that herbal medicines might be of effective benefit in the
treatment of certain diseases where conventional therapies and
medicines have proven to be inadequate;
IL.
111.
Iv.
. tendency towards self-medication;
. improvement in quality, proof of efficacy and safety of herbal
medicines;
VI
VIILhigh cost of synthetic medicines.
صفحه 11:
Standardization of botanical herbs and
quality of botanical preparations
Plants contain several hundred constituents and some of them are
present at very low concentrations. In spite of the modern chemical
analytical procedures available, only rarely do phytochemical
investigations succeed in isolating and characterizing all secondary
metabolites present in the plant extract. Apart from this, plant
constituents vary considerably depending on several factors that
impair the quality control of phytotherapeutic agents. Quality control
and standardization of herbal medicines involve several steps.
However, the source and quality of raw materials play a pivotal role in
guaranteeing the quality and stability of herbal preparations. Other
factors such as the use of fresh plants, temperature, light exposure,
water availability, nutrients, period and time of collection, method of |
collecting, drying, packing, storage and transportation of raw material,
age and part of the plant collected, etc., can greatly affect the quality
and consequently the therapeutic value of herbal medicines.
صفحه 12:
= Some plant constituents are heat labile and the plants
containing them need to be dried at low temperatures. Also,
other active principles are destroyed by enzymatic processes
that continue for tong periods of time after plant collection. This
explains why frequently the composition of herbally based drugs
is quite variable. Thus, proper standardization and quality
control of raw material and the herbal preparations themselves
should be permanently carried out. In the cases where the active
principles are unknown, marker substance(s) should be
established for analytical purposes. However, in most cases
these markers have never been tested to see whether they really
account for the therapeutic action reported for the herbal drugs.
As pointed out before, apart from these variable factors, others
such as the method of extraction and contamination with
microorganisms, heavy metals, pesticides, etc., can also |
interfere with the quality, safety and efficacy of herbal drugs.
صفحه 13:
= For these reasons, pharmaceutical companies prefer using
cultivated plants instead of wild-harvested plants because they
show smaller variation in their constituents. Furthermore and
certainly more relevant; when medicinal plants-are-produced by
cultivation, the main secondary metabolites can be monitored
and this permits definition of the best period for harvesting.
= The recent advances which occurred in the processes of
purification, isolation and structure elucidation of naturally
occurring substances have made it possible to establish
appropriate strategies for the analysis of quality and the process
of standardization of herbal preparations in order to maintain as
much as possible the homogeneity of the plant extract. Among
others, thin-layer chromatography, gas chromatography, high-
performance liquid chromatography, mass spectrometry,
infrared-spectrometry, ultraviolet/visible spectrometry, etc.,
used alone or in combination, can be successfully used for |
standardization and to control the quality of both the raw |
material and the finished herbal drugs.
صفحه 14:
Regulatory aspects and approval
of herbal drugs
= The legal process of regulation and legislation of herbal medicines
changes from country to country. The reason for this involves
mainly cultural aspects and also the fact that herbal medicines are
rarely studied scientifically. Thus, few herbal preparations have
been tested for safety and efficacy. The WHO has published
guidelines in order to define basic criteria for evaluating the
quality, safety, and efficacy of herbal medicines aimed at assisting
national regulatory authorities, scientific organizations and
manufacturers in this particular area. Furthermore, the WHO has
prepared pharmacopeic monographs on herbal medicines and the
basis of guidelines for the assessment of herbal drugs.
صفحه 15:
Regulatory aspects and approval of
herbal drugs in USA
Since 1994, herbal medicines have been regulated under
the “Dietary Supplement Health and Education Act of
1994”. On the basis of this law, herbal medicines are not
evaluated by the Food and Drug Administration and, most
important, these products are not intended to diagnose,
treat, cure, or prevent diseases. The US government has
established the “Office of Alternative Medicine” at the
National Institutes of Health (NIH) with the following
aims: 1) to explore the potential role of dietary
supplements in the improvement of health; 2) to promote
the scientific study of supplements for maintaining health
and preventing chronic diseases; 3) to compile a database
صفحه 16:
Regulatory aspects and approval of
herbal drugs in Germany
= Germany’s Commission E (phytotherapy and herbal
substances) was established in 1978. It is an independent
division of the German Federal Health Agency that collects
information on herbal medicines and evaluates them for
safety and efficacy. The following methods and criteria are
followed by Commission E: 1) traditional use; 2) chemical
data; 3) experimental, pharmacological and toxicological
studies; 4) clinical studies; 5) field and epidemiological
studies; 6) patient case records submitted from physician’s
files, and 7) additional studies, including unpublished |
proprietary data submitted by manufacturers.
صفحه 17:
= The composition of Commission E is as follows: physicians,
pharmacists, pharmacologists (pharmacognosist), toxicologists,
industry representatives and laypersons, for a total of 24
members. Two possibilities for marketing herbal drugs exist: 1)
temporary marking authorization for old herbal drugs until
they are evaluated for safety and efficacy; and 2) monographs
of standardized marketing authorization. Evaluations are
published in the form of monographs that approve or
disapprove the herbal drugs for use. Herbal medicines are sold
in pharmacies, drugstores and health food stores. Some herbal
medicines are controlled by a physician’s prescription.
= Commission E has published about 300 monographs and about
600-700 plants are sold in Germany. Approximately 70% of
physicians prescribe registered herbal drugs. Part of annual
sales is paid for by government health insurance.