1
NATURAL MEDICINES
Medicines from plants
• Fresh plants or their parts (Myrtilli fructus recens)
• Dried plants or their parts = drugs
• Isolates from fresh plants and drugs (chemically defined compounds)
Medicines from animals (mostly isolates)
Medicines from marine organisms(Plexaura homomala – prostaglandins)
Medicines obtained by biotechnology (enzymes, hormones, cytokines, monoclonal
antibodies, inhibitors of tyrosinkinase…)
PHYTOPHARMACEUTICALS
„Pharmaceuticals exclusively or predominantly composed from plants, plant parts
and content compounds from plants, if they are not listed in homeopathic or
anthroposophic groups“. Rudolf Hänsel
- Chemically uniform compounds (atropine, VLB, taxol …)
- Chemically nonuniform (drugs, essential oils, resins, oils …)
Key importance for quality has a technological process for manufacturing
Valerianae radix water = hydrophilic compounds without sedative
effect
chloroform = sedative valepotriates
Pharmaceutical and medical research intensively make a point of
identification of main active content compound and its quantification
in final medicinal formulation.
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THERAPY – EFFECT
management of
THERAPY → medicine → changes pathological condition
prevention of
wanted unwanted
etiologic
(specific, cauzal)
chemopathogenetic
THERAPY
phyto-
symptomatic
EFFECT
non-specific specific
(conditioned by some general phys.-chem.
- Oils – lubricants, laxatives)
(effect based on chemical configuration
of characteristic molecule
= receptor – bond – effect [QSAR]
THERAPY
radical
THERAPY
psychoconservative
balneopharmaco-
(cca 80 %)
phyto chemo
origin
methods
scientific disciplines
PATIENT
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PHYTOPHARMACEUTICALS
No law-defined definition for phytopharmacuticals.
Germany:
• Medicines exclusively or predominantly composed from plants,
palt parts, plant content compounds (generaly drugs with nonorganised
structure as it is resine or essential oil) if these are
not listed in homeopatic anad anthroposophic groups of
compounds.
• Medicines of plant origin including plant isolates (chemical
individua) with defined structure.
PHYTOPHARMACEUTICALS, PHYTOTHERAPY
EMA (EMEA) – European Medicines Agency
FDA - Food and Drug Administration
Phytopharmaceuticals – exclusively or predominantly composed from
plants, plant parts, plant content compounds
1. Effect proved
2. Proof of effect missing
WHO – phytopharmaceuticals are not belonging to essential drugs
¨range of products in individual countries different
PHYTOTHERAPY – part of therapy overall. Phytodiagnostic does not exist.
Phytotherapy is chemotherapy which uses compounds
biosynthesized by plants. Phytopharmaceuticals possess wide
therapeutic range – indication according to the „officinal“ medicine.
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NATURAL MEDICINES AND MATERIAL FOR THEIR
PREPARATION
• MEDICINAL PLANT – such as plant, which is used whole or its parts in different forms
directly for treatment of diseases, or as a material for medicaments preparation. Fresh
medicinal plants, their parts or products are used for therapy exceptionally.
• DRUG – dried, alternatively conserved by different way, modified or un-modified plant
(animal), or its organ or part, alternatively its product, which serves for manufacturing
medicaments or technically important compounds, or directly used for therapeutical,
technical, or other purposes.
• PARTES USUALES – collected and used parts of plants, in which the biologically active
compound is in the highest amount.
NOMENCLATURE OF DRUGS
Nomenclature of drugs is usually binomic (similarly to the nomenclature of botany)
• First word represents the genus, to which the mother plant belongs (Malvae folium, Strychni
semen, Stramonii folium).
- incial letter big, genitive
• Second word represents the name of plant organ (Betulae folium, Ononidis radix)
- inicial letter small, singular
• Mother plant precisely named in drug definition (Malva silvestris L., Malva neglecta WALLR.)
• Names of essential oils, oils and starches are derived in cited way: Anisi etheroleum – Anise
essential oil; Olivae oleum – olive oil; Solani amylum – potatoe starch
• Exceptions:
Name is created from one word only: Lupulinum, Lycopodium
Traditional name, which is not in correspondance with name of plant: Liquiritiae radix –
Lycorice root
• Previously used nomenclature is still in use for balms: Balsamum peruvianum – Balsam of
Peru
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DRUG DIVISION
ACCORDING TO THE ORIGIN
• plant (vegetabile)
• animal
ACCODING TO THE STRUCTURE
• Drugs with organized structure
majority of plant drugs and partly animal drugs, showing cellular constitution – from one cell to set
of tissues in constant order: Lupulinum, Lichen islandicus, Belladonnae radix
• Amorphous drugs
different plant and animal drugs, without cellular organization. Are derived as:
physiologic products: Resina mastix,
pathologic products: Balsamum peruvianum
products obtained from raw material by destillation (Menthae etheroleum), melting (Adeps suillus),
stamping (Olivae oleum), extraction (Chrysarobinum), thickening (Liquiritiae succus)
ACCORDING TO THE USAGE
• Drugs therapeutical (used for medicaments preparation or for isolation of effective compounds)
• Drugs utilitarian (manufacturing of colors, tannery, food industry, cosmetics)
CONTENT COMPOUNDS
• Compounds effective, active principles, main compounds (pharmacodynamics)
• Co-effectors, affecting main compounds (pharmacokinetics)
• Dietetics (sugars, fats, proteins)
• Adjuvants (starches, gums)
• Accompanying compounds (lignine, pigments, Ca oxalate)
• Balast compounds
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Drug
Fresh plant, or its part
Medicinal wine Pressed juice Oil concentrate
Macerate while cold
Water extract
Infusion
Decoction
Instant products
Externals
(ointments, balsams,
cataplasms)
Medicinal Teas
Essential oils
Cosmetics
Aromatic spirits
Pulverized drug
Tincture
Extract
Liquid
Semi-liquid
Solid (dried)
Extract of
lipohilic fraction
Lipophilic solvents
EtOHWater
Distillation
Water EtOH
Treatment Of Fresh Plants, Their Parts And Drugs
PREPARATION FROM FRESH PLANTS OR THEIR ORGANS
PLANT JUICES
• Maceration in water, pressing, pasteurization, uperization
• Containing hydrophilic compounds (sugars, vitamins, amino acids, organic
acids…)
• Do not contain strongly effective compounds
• Freely distributed, self-treatment
HOMEOPATIC TICKTURES
• Maceration in 90% EtOH, pressing URTINCTURE (allopatic)
• Preparation according to HAB and Ph.Eur.
for example Nux vomica Ф = D1 equivalent Strychni tinctura
• dilution, potentiation, dynamisation, infinitesimal doses
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WATER EXTRACTS
Drug(s) : water = 1:3; 1:5; 1:10
Boiling Decoction Decoctum (ligna, radices, semina, fructi)
30 min. at 90 0C (water bath)
- drug + cold water, slow increase of temperature, boil 10 – 15 min, next 15
min. extraction
Infusion Infusum (extraction at temperature decreasing from boiling point to room temperature)
Maceration Maceratum (maceration (soaking) of drug in liquid to extract soluble parts and to get
extract (macerate)
Drugs containing mucilage – pass with defined amount of water at temp. cca 20 0C, 30 min.
maceration, decantation
INSTANT TEAS
Extracta aquosa sicca = granulations (vacuum, lyophilisation)
Extracta aquosa spissa seu fluida = paste
Additional compounds – lipophilic compounds (essential oil)
Most often preparations for treatment of stomach disorders
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SPECIES – TEAS
1. Remedium basis
2. Remedium adjuvans maximum 4 to 6 drugs
3. Remedium corrigens
Effect of medicinal tea is ensured by qualitative parameters of drugs (effective compounds
quantified) and keeping the recommended conditions for preparation and usage.
Drugs for tea mixtures
1. Prescription only
2. Without prescription
3. Marketed out of pharmacy (without indication)
4. Cannot be used
1-4: Qualitative criterions according to ČL 2002; ON
Back to nature:
Plant medicines are not almighty and are not harmless!!
ALCOHOL EXTRACTS
ČL 2002 – Suppl. 2003
EXTRACTS – extract from drug (macerate, percolate) with more or less
removed extraction medium.
Extracts can be divided:
• Liquid (liquid extracts and tinctures) - drug : EtOH = 1:5; 1:10;
Extractum fluidum (extractive compounds from 1 portion of drug are
contained in 1, maximally 2 portions of extract.
• Semi-liquid (thick extracts) Extractum spissum (original, non-modified
extracts, containing 15 – 25 % residual solvents.
• Solid (dried extracts) - Extractum siccum (with max. content of 5 % of
residual solvents).
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TYPES OF EXTRACTS
• Standardized extracts – are modified to contain required of
compounds with known therapeutic potential; standardization is
carried out using inert compounds or by mixing different
extracts (different batch).
• Quantified extracts – corrected to required content of desired
compounds.
• Other extracts – are defined especially by manufacturing
procedure (characteristics of plant or animal drug used for
extraction, type of solvent and extraction conditioning) and its
properties.
THERAPEUTIC EFFECT IS AFFECTED BY:
• Type of drug and by content of effective compounds
• Manufacturing of drug into final preparation
• Changes of effective compounds in GIT
• Specifity of effective compounds
• Kinetics of effective compounds
• Dosage and tolerance
• Accumulation of effective compounds in organism
• Synergism or antagonism
• Status of patient
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FOLK MEDICINE, SELF-TREATMENT
Risks of ignorance
• Impossibility of correct diagnose?
• Choice of medicament?
• Dosage?
• Period of therapy?
• Knowledge of practical experience
REQUIREMENTS ON PHYTOPHARMACEUTICALS
REGISTRATION
Development in area of pharmaceuticals is very intensive.
authorized use
Research → materials → pharm. industry → medicaments deceptions
tragedies (thalidomid)
Contergan - terathogenic
REGISTRATION IN CZECH REPUBLIC – STATE INSTITUTE FOR DRUG CONTROL
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REQUEST FOR REGISTRATION AS LARGE SCALE
MANUFACTURED DRUG
1. BASIC DATA 3. PHARMACEUTIC-TECHNOLOGIC DOCUMENTS
Name of preparation quantitative composition of medicament
Drug form manufacturing description
Name and address of manufacturer, applicant drug specification according to Eur. Ph. Or branch norm
Company responsible for marketing determination of pesticide residues
Datum, signature
2. BASIC CHARACTERISTICS 4. CONTROL OF FINAL PREPARATION
Composition (Czech, Latin, INN Assays and procedures for phys.-chem. methods
of effective compounds and adjuvants) according to Eur. Ph.
Pharmacologic data (indication, Microbial assays
contraindication, dosage, exceptional data Biological assay
– pregnancy, breast-feeding…)
Pharmaceutical data (description of preparation,
type of package, size of package, expiration,
storage)
REQUEST FOR REGISTRATION AS LARGE SCALE
MANUFACTURED DRUG
5. STABILITY STUDIES
Description
Possible products of decomposition
Results according to different conditions of keeping and storage
6. TOXIKOLOGIC AND PHARMACOLOGIC DOCKUMENTATION
7. CLINICAL DOCUMENTATION
8. CERTIFICATION ABOUT REGISTRATION
9. CERTIFICATION OF MANUFACTURER ABOUT GMP
10. MISCELANEOUS
Original package including leaflet
Samples (including referential standards) for 3 full analyses
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CLINICAL ASSAYS OF PHYTOPHARMACEUTICALS
All rules for clinical pharmacology are valid:
1. Definition of disease and symptoms
2. The matter of clinical assay, the time limits
3. To know the exact composition of phytopharmaceutic, chemical structure of compound,
presumed therapeutic effect
4. To determine if the test will be individual, with placebo, or with known therapeutic
6. To determine daily doses, time of administration with regard to possible effect of feeding
7. Number and selection of patients (ambulant – hospitalized / acute – chronic
8. Type of study (opened, simply or double blindened)
9. Definitions of criterions for effect evaluation (value of blood pressure, level of serum
lipoproteins….)
10. The way of analysis of acquired results, definition of criterions of effectiveness
11. Exclusion of extra pharmacological effects
12. To monitor the time of start and duration of effect
13. Topic preparations – dermatotropic activity
CLINICAL ASSAYS
• For all newly used drugs
• For plant species till present not used for medicals preparation
• Drug with unknown content compounds
• Known drug till present does not used as medicinal
• New indications of known phytopharmaceuticals
• Foreign drugs non-registered in Czech Republic
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APPROVAL OF NEW MEDICINES
New drug is important factor, which can affect improvment of health
status and quality of life, and possibly to safe the life. Therefore the
attention is laid also on duration of approval process to imply new drug
on market. This is defined as overall number of calendar days from
application to issue the approval. From the monitoring of duration of
approval process for 70 new chemical entities, which were under
approval process 1995-1999 can be deduced: median of duration of
approval process in Australia (43 new drugs) was 25,3 of month,
in Canada (70) 29,4 of months, in Sweden (48) 27,3 months, Great Britain
(54) 11,7 of months and in USA (57 ne drugs) 25,5 of months.
Duration of approval process is not significantly affected by therapeutic
classification, number of required and additional information or datum
of application.
Pieterson E.A.: J Clin Pharmacol, 32, 2002 s. 889