COMMUNITY HERBAL MONOGRAPH ON
PRIMULA VERIS
L. AND
PRIMULA ELATIOR
(L.) HILL, FLOS
To be specified for the individual finished product.
Well-established use
Traditional use
With regard to the marketing authorisation
application of Article 10(a) of Directive
2001/83/EC as amended
With regard to the registration application of
Article 16d(1) of Directive 2001/83/EC as
amended
Primula veris
L. and/or
Primula elatior
(L.)
Hill, flos (primula flower)
ii)
Herbal preparations
- Liquid extract (1:1, extraction solvent
ethanol 25% (V/V))
- Comminuted herbal substance for tea
preparation
i)
Herbal substance
Whole or cut, dried flowers
Well-established use
Traditional use
Herbal substance or comminuted herbal substance
for tea preparation or other herbal preparation in
liquid and solid dosage forms for oral use.
The pharmaceutical form should be described by
the European Pharmacopoeia full standard term.
4.
C
LINICAL
P
ARTICULARS
4.1. Therapeuticindications
Well-established use
Traditional use
Traditional herbal medicinal product used as an
expectorant in cough associated with cold.
The product is a traditional herbal medicinal
1
The declaration of the active substance(s) for an individual finished product should be in accordance with
relevant herbal quality guidance.
©
EMEA 2007
2/5
product for use in specified indication exclusively
based upon long-standing use.
4.2 Posology and method of administration
Well-established use
Traditional use
Posology
Adolescents over 12 years of age, adults, elderly
single dose daily dose
Herbal substance for
tea preparation
1 g
2-4 g
Comminuted herbal
substance for tea
preparation
1 g
2-4 g
Liquid extract
1-3 ml
3-6 ml
Dosage frequency: 3 times daily
The use is not recommended in children under 12
years of age (see 4.4 Special warnings and
precautions for use).
Duration of use
Adolescents over 12 years of age, adults, elderly
Medical attention should be sought if after 1 week
of treatment the symptoms do not improve.
If the symptoms persist during the use of the
medicinal product, a doctor or a qualified health
care practitioner should be consulted.
Method of administration
Oral use.
Tea preparation: 1 g of herbal substance or
comminuted herbal substance for infusion.
As an expectorant one cup of tea up to 3 times
daily.
4.3.
Contraindications
Well-established use
Traditional use
Hypersensitivity to the active substance or to
other Primula species.
Children with a history of acute obstructive
laryngitis.
Asthma.
©
EMEA 2007
3/5
4.4.
Special warnings and precautions for use
Well-established use
Traditional use
The use is not recommended in children under 12
years of age because no data on safety are
available.
Caution is recommended in patients with gastritis
or gastric ulcer.
If dyspnoea, fever or purulent sputum occurs, a
doctor or a qualified health care practitioner
should be consulted.
For extracts
containing ethanol, the appropriate
labelling for ethanol, taken from the ‘Guideline on
excipients in the label and package leaflet of
medicinal products for human use’, must be
included.
4.5.
Interactions with other medicinal products and other forms of interaction
Well-established use
Traditional use
None reported.
4.6.
Pregnancy and lactation
Well-established use
Traditional use
Safety during pregnancy and lactation has not
been established. No adverse effects have been
reported from the use of Primula flower as a
medicinal product during pregnancy and lactation.
In the absence of sufficient data, the use during
pregnancy and lactation is not recommended.
4.7.
Effects on ability to drive and use machines
Well-established use
Traditional use
No studies on the effect on the ability to drive and
use machines have been performed.
4.8.
Undesirable effects
Well-established use
Traditional use
Gastric disorders, nausea, vomiting and allergic
reactions may occur. The frequency is not known.
If other adverse reactions not mentioned above
occur, a doctor or a qualified health care
practitioner should be consulted.
©
EMEA 2007
4/5
Well-established use
Traditional use
Overdose may lead to stomach upset, vomiting or
diarrhoea.
5.
5.1
Pharmacodynamic properties
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
5.2
Pharmacokinetic properties
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
5.3
Preclinical safety data
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended, unless
necessary for the safe use of the product.
Tests on reproductive toxicity, genotoxicity and
carcinogenicity have not been performed.
Well-established use
Traditional use
Not applicable.
7.
D
ATE OF
C
OMPILATION
/L
AST
R
EVISION
7 September 2007
©
EMEA 2007
5/5
Assessment Report
ASSESSMENT REPORT
FOR HERBAL SUBSTANCE(S), HERBAL PREPARATION(S) OR COMBINATIONS
THEREOF WITH TRADITIONAL USE
Primula veris
L.,
Primula elatior
(L.) Hill, flos
BASED ON ARTICLE 16D(1) AND ARTICLE 16F AND 16H OF DIRECTIVE
2001/83/EC AS AMENDED
Herbal substance(s) (binomial scientific name
of the plant, including plant part)
Primula veris
L.,
Primula elatior
(L.) Hill, flos
Herbal preparation(s)
Liquid extract (1:1, extraction solvent ethanol
25%, v/v)
Comminuted herbal substance
Pharmaceutical forms
Herbal substance or comminuted herbal
substance for tea preparation or other herbal
preparation in liquid and solid dosage forms for
oral use.
Rapporteur
Heribert Pittner
Assessors
Johann Krisper
Reinhard Länger
EMA 2010
2/11
1
INTRODUCTION
1.1
Description of the traditional herbal substance(s), herbal preparation(s) or
Herbal substance
Primula flower (Primulae flos)
Whole or cut, dried flowers including the calyx or without calyx of
Primula veris
L. and/or
Primula
elatior
(L.) Hill for oral administration. The material complies with the German Deutscher
Arzneimittel Codex (DAC 2006).
Some references restrict the plant source to the species
Primula veris
(British Herbal Pharmacopoeia
(1983), Pharmacopée Française X
e
édition).
The haemolytic index (HI) has been used for biological standardisation of saponin containing herbal
substances and herbal preparations. Although no longer in use the HI facilitates a comparison between
the HI of a herbal drug and preparations thereof and allows an estimation of the saponin content.
HI of Primulae flos: 35
Constituents
(Hänsel et al. 1994), Wichtl 2004):
Triterpene saponins (in the sepals up to 2%); structural details are missing.
Flavonoids (in the petals up to 3%): apigenine, rutoside (1.3% in
P. elatior
, 0.16 % in
P. veris
),
quercetagenin-3-gentiobioside, 3’,4’,5’ – trimethoxyflavone; kaempferol-3-rutinosid and
isorhamnetin-3-glucoside present in flowers of
P. elatior
only.
Carotenoids, traces of essential oil, rosmarinic acid, D- volemitol and other sugar alcohols.
HO
O
HO
O
O
Rutino
OH
O
OH
O
Apigenin
Rutoside
The aerial parts may contain primin and other quinoid compounds, which are responsible for
contact allergenic properties of species of the genus Primula (Hausen 1978).
OH
H
H
O
HO
H
HO
HO
OH
H
3
CO
HO
H
OH
H
O
Volemitol
Primin
EMA 2010
3/11
combinations thereof
Herbal preparations with evidence of traditional use
Liquid extract (1:1, extraction solvent 25% ethanol (v/v), cited in the British Herbal Pharmacopoeia)
Assessors comment: no details could be found on the tincture which is cited in the publications of the
Commission E.
Combinations of herbal substance(s) and/or herbal preparation(s)
Primula flower extracts are used in combinations with many other herbal substances/herbal
preparations. This monograph refers exclusively to Primula flower.
Vitamin(s)
Not applicable
Mineral(s)
Not applicable
2
TRADITIONAL MEDICINAL USE
2.1
Information on period of medicinal use in the Community regarding the specified
Data concerning the medicinal use of Primula flower in Europe go back to the beginning of the 20
th
century (Zörnig 1911), Dinand 1921). The herbal substance and preparations are also mentioned in
Hager’s Handbuch (List & Hörhammer 1977). Therefore it can be stated that the crude drug is
continuously in medical use since about 100 years.
Therefore, for Primula flower a period of at least 30 years in medical use as requested by Directive
2004/24/EC for the qualification as a traditional herbal medicinal product is easily fulfilled.
2.2
Type of tradition, where relevant
European tradition.
EMA 2010
4/11
indication
2.3
Bibliographic/expert evidence on the medicinal use
2.3.1
Evidence regarding the indication/traditional use
The following indications have been reported for Primula flower:
Ailments of the airways:
Cough
List & Hörhammer (1977),
Catarrhs of respiratory
tract
Hänsel et al. (1994); Commission E (1990), Wichtl (2004),
DAC (2006)
Expectorant for coughs
and bronchitis
Wichtl (2004), Zörnig (1911)
Further indications:
Nervousness
List & Hörhammer (1977), Wichtl (2004), Fournier (1948),
Zörnig (1911), Hänsel et al. (1994), British Herbal
Pharmacopoeia (1983)
Headache
Wichtl (2004), Flamm et al. (1940), Zörnig (1911), Hänsel et
al. (1994)
As a diaphoretic
Dinand (1921), List & Hörhammer (1977)
Rheumatism
List & Hörhammer (1977), Zörnig (1911)
Gout
List & Hörhammer (1977), Zörnig (1911)
As a diuretic
Zörnig (1911), Auster & Schäfer (1961)
Plausibility of actions: saponins are only present in the sepals; therefore for the indication ‘cough’ the
complete flowers must be used.
Further constituents do not support other traditional indications.
Based on the available literature and the known actions of saponins, the following text on the
indication is recommended:
“Traditional herbal medicinal product used as an expectorant in cough associated with cold.
The product is a traditional herbal medicinal product for use in specified indication exclusively based
upon long-standing use.”
2.3.2
Evidence regarding the specified strength
Primula flower is usually used in combination with other herbal substances. The content of Primula
flower in herbal preparations varies in herbal teas from 10% to 30%, in liquid preparations it is about
1% and in solid dosage forms about 8%.
2.3.3
Evidence regarding the specified posology
Posology in adults:
Herbal substance
reference
single dose
daily dose
British Herbal Pharm. (1938)
1-2 g as infusion, 3 times daily
Wichtl (2004)
1 teaspoon = 1.3 g
2-4 g
Ergänzungsbuch 6 (1941)
1 g
DAC (2006)
1 teaspoon = 1.3 g
2.6-3.9 g
List & Hörhammer (1977)
single dose 1 g
Hänsel et al. (1994)
single dose 1 g
3 g
Auster & Schäfer (1961)
1 g
Commission E
2-4 g
1 Teaspoon = approximately 1.3 g
EMA 2010
5/11
Herbal preparations
reference
single dose
daily dose
Tincture
Commission E (1990)
0.8-2.5 g
2.5-7.5 g
Liquid extract
British Herbal Pharm. (1983)
1-2 ml, 3 times daily
3-6 ml
Based on these references, the following posology is recommended for adolescents over 12 years of
age, adults and elderly:
single dose
recommended mean
daily dose
Comminuted herbal substance
for tea preparation
1 g
2-4 g
Liquid extract
1-3 ml
3-6 ml
Dosage frequency: May be taken 3 times daily
Posology in children:
The posology presented in Dorsch et al. (2002) is calculated.
The au
thors propose for the herbal substance as mean daily dose:
herbal substance,
mean daily dose
0-1 year
0.5-1 g
>1-4 years
1-2 g
>4-10 years
2-3 g
>10-16 years
2-4 g
No data for a posology in children from clinical trials are available. Therefore Primula flower should
not be used in children up to 12 years. Since data available for Primula root suggest a use for children
from 1 year of age, a use of Primula flower from 12 years could be justified.
See 2.5.2 Special warnings.
2.3.4
Evidence regarding the route of administration
The oral administration is the only route of administration for Primula flower preparations in the
recommended traditional indication.
2.3.5
Evidence regarding the duration of use
No restriction on the duration of use has been reported for Primula flower.
Adolescents over 12 years of age, adults, elderly
Medical attention should be sought if after 1 week of treatment the symptoms do not improve.
If the symptoms persist during the use of the medicinal product, a doctor or a qualified health care
practitioner should be consulted.
EMA 2010
6/11
2.4
Assessor’s overall conclusion on the traditional medicinal use
Preparations from Primula flower have been used for the relief of symptoms of the upper respiratory
tract in coughs associated with cold for many decades. Since the clinical documentation is poor and no
controlled clinical studies are available, the use of Primula flower preparations has to be regarded as
traditional
.
2.5
Bibliographic review of safety data of the traditional herbal medicinal
substances/preparations
2.5.1
Patient exposure
No exact data on patient exposure are available.
2.5.2
Adverse events
All cited references (e.g. Hänsel et al. 1994, Commission E, Hänsel & Sticher 2007) agree that in
single cases gastric disorders and nausea may occur.
Contact allergic properties have been described for primin and other quinoid compounds which may
be present in the aerial parts of
Primula elatior
and
Primula veris
(Hausen 1978). For both species,
primin-free as well as primin-containing individuals are reported (Hausen 1978, Fregert & Hjorth
1977). Hypersensitivity against primin could be of clinical relevance.
The search in the database of the Austrian Medicines and Medical Devices Agency AGES PharmMed
(access date: 12 December 2006) had only 3 reports of adverse effects referring to preparations
containing Primula. All reports concern the product Sinupret
®
, which is a combination of a liquid
extract of Primulae flos and four other herbal preparations (Gentianae radix, Rumicis herba, Sambuci
flos, Verbenae herba). The adverse effects cannot be exclusively assigned to Primula flower, the
contribution of the combination partners is not known. In 2 cases, the application of Sinupret
®
caused
allergic reactions (rash, face oedema), the third report refers to an anaphylactic shock after
concomitant use of Sinupret
®
, Novalgin
®
, Parkemed
®
and Tricef
®
, which cannot be causally assigned
to the presence of Primula. These reports are not relevant for preparations containing Primulae flos as
the only active ingredient.
In the WHO database (access December 2006), one report of allergic reaction after ingestion of
Primula flower is listed, the type of preparation is not mentioned.
Wording for the monograph:
Special warnings:
The use is not recommended in children under 12 years of age because no data on safety are available.
Caution is recommended in patients with gastritis or gastric ulcer.
If dyspnoea, fever or purulent sputum occurs, a doctor or a qualified health care practitioner should be
consulted.
For extracts containing ethanol, the appropriate labelling for ethanol, taken from the ‘Guideline on
excipients in the label and package leaflet of medicinal products for human use’, must be included.
Undesirable effects:
Gastric disorders, nausea, vomiting and allergic reactions may occur. The frequency is not known.
If other adverse reactions not mentioned above occur, a doctor or a qualified health care practitioner
should be consulted.
EMA 2010
7/11
2.5.3
Serious events and deaths
None known for Primula flower preparations for oral administration.
The anaphylactic shock observed after the concomitant application of Sinupret
®
, Novalgin
®
,
Parkemed
®
and Tricef
®
cannot be causally assigned to Primulae flos present in Sinupret
®
.
2.5.4
Safety in special populations and situations
2.5.4.1
Intrinsic (including elderly and children)/extrinsic factors
None known.
2.5.4.2 Drug-drug interactions and other interactions
Saponins in general are considered to enhance the absorption of other substances in the gastro-
intestinal tract (Hänsel & Sticher 2007). It is assumed that saponins reduce the particle size of
substances which are poorly soluble in water. In addition, the irritation of the mucous layer may ease
the diffusion of other substances. It is postulated that these effects may be of relevance for flavones,
phytosterols and silicic acid, but systematic investigations are lacking. No specific data are available
for the saponins of Primula species. Walthelm et al. (2001) studied the effect of saponins on the water
solubility of model compounds. The Primula saponins showed no clear dose-dependent effect. The
authors conclude that saponins in general should not be regarded as solubilisers.
The dietary intake of saponins has been estimated as 10 mg per person per day in an average UK
family. For vegetarians the figure is substantially higher, sometimes exceeding 200 mg per person per
day (Hostettman & Marston 1995). Saponins administered with preparations of Primulae flower (4 g
with 2% saponins in the sepals only) exceed slightly the one of typical dietary intake. It is not known
whether this increase affects the absorption of other drugs.
No studies on interactions with other medications have been performed. No interactions have been
reported.
2.5.4.3 Use in pregnancy and lactation
Safety during pregnancy and lactation has not been established. No adverse effects have been reported
from the use of Primula flower as a medicinal product during pregnancy and lactation.
In the absence of sufficient data, the use during pregnancy and lactation is not recommended.
2.5.4.4 Overdose
Overdose may lead to stomach upset, vomiting or diarrhoea.
2.5.4.5
Drug abuse
None known.
2.5.4.6
Withdrawal and rebound
None known.
2.5.4.7
Effects on ability to drive and use machines
No studies on the effect on the ability to drive and use machines have been performed.
2.5.4.8
Contraindications (hypersensitivity and allergic potential to be both covered)
Hypersensitivity to the active substance or to other Primula species.
Children with a history of acute obstructive laryngitis.
Asthma.
EMA 2010
8/11
2.5.5
Non-clinical safety data
2.5.5.1
Overview of available data regarding the herbal substance(s), herbal preparation(s)
Oral toxicity
There are no Primula-specific toxicity data available.
In the United States, flowers of
Primula veris
and
P. elatior
are classified as Class 1, which means
they can be safely consumed when used appropriately (McGuffin et al. 1997).
Data on saponins in general:
After oral administration of saponins no signs of absorption of toxic doses have been found. Damages
in liver metabolism and fatty degeneration of kidney cells were observed during
in vivo
studies in rats
with higher oral doses of saponins (Vogel 1963).
The oral toxicity of saponins in mammals is relatively low due to their poor absorption. LD
50
values
are in the range of 50 mg/kg (which is not very low when the figures are correct) and 1000 mg/kg
(Hostettman & Marston 1995; Oakenfull 1981).
The dietary intake of saponins has been estimated as 10 mg per person per day in an average UK
family. For vegetarians the figure is substantially higher, sometimes exceeding 200 mg per person per
day. With a few exceptions (such as liquorice), no negative effects are apparent from prolonged intake
of edible plants containing saponins. Primula saponins are considered to have a favourable benefit-risk
ratio (Hostettman & Marston 1995).
Chibanguza et al. (1984) have performed
in vivo
studies on rabbits which contain some information
concerning toxicological considerations. Except for the red blood count, none of the parameters tested
(rate of breathing, pulse rate, Quick-%-value, electrolyte concentrations of calcium, potassium,
sodium) was influenced by the intragastral application of the extract from Primulae flos in the 50-fold
therapeutic concentration.
Parenteral toxicity, toxicity of topical application
Hänsel et al. (1994) give toxicological data on Primula root: there are only LD values for the saponin
fraction from
P. veris
(LD
50
mouse,
i.p.
24.5 mg kg
-1
b.w.) or for primula acid (LD
50
rat,
i.v.
1.2 mg
kg
-1
b.w.) available, which have no relevance for the oral administration of Primula flower
preparations. Saponins damage the cell membranes: this results in local irritation and, at higher doses,
in cytotoxicity. After parenteral administration, haemolysis with liver and kidney lesions, cardiac
dilatation and circulatory failure may occur. Local irritating effects have been observed on the rabbit
cornea.
According to Vogel (1963), the parenteral toxicity is not correlated with the haemolytic index of the
saponins
in vivo
(rats).
Other toxicity data
There are no data on genotoxicity, carcinogenicity, reproductive and developmental toxicity
published.
2.5.6
Assessor’s overall conclusions on safe use
The oral administration of Primula flower preparations can be regarded as safe, especially at
therapeutic doses; the contact allergic properties of different Primula species can cause rarely allergic
reactions. The data available from pharmacovigilance databases do not show a serious risk for the use
of Primula flower.
EMA 2010
9/11
and relevant constituents thereof
3
3.1
Overview of pharmacological effects of herbal substance(s), herbal preparation(s)
The mode of the expectorant action of Primula saponins is not yet satisfactorily clarified. In literature,
there is a general agreement that saponins irritate locally the gastric mucosa, which provokes a reflex
increase in bronchial secretion, and subsequently dilutes the mucus and reduces its viscosity (Hänsel et
al. 1994, Boyd 1954, Hänsel & Sticher 2007, ESCOP 2003). Irritation of mucous membranes in the
throat and respiratory tract by saponins may also cause an increase in bronchial secretion. In addition,
the surface-tension lowering action of saponins might help to reduce the viscosity of the sputum,
facilitating its ejection (Hostettman & Marston 1995).
Recently, a very specific influence on the
2
-adrenergic receptors of alveolar cells has been reported
for the saponins of
Hedera helix
, which is used for the same indications like Primula root (Häberlein
& Prenner 2005). At present, it is not known whether these effects are restricted to the saponins of
Hedera.
In vitro
experiments
Most of the published
in vitro
experiments deal with the antiviral, antimycotic and antibacterial
activity, which are common properties of saponins independent of their plant source.
Wolters (1966) has compared the antifungal and antibacterial effects of 30 herbal drugs containing
saponins. Among them, Primula root extracts belonged to the group of extracts with the most
pronounced fungistatic or fungicide effects, while the antibacterial effect was considerably lower. The
author suggested that saponins may act as important resistance factors of the plants.
Tschesche & Wulff (1965) described both antifungal and antibacterial effects (e.g. against
Staphylococcus aureus
,
Escherichia coli
) of saponins from
Primula elatior
.
The total saponins isolated from
Primula acaulis
(=
P. vulgaris
Huds.) were effective against various
strains of
Candida albicans
at concentrations of 80 – 97 µg/ml (Margineanu et al. (1976). The
antimycotic effect of these saponins is quantitatively less than that of the typical antimycotics
nystatine and stamicine. The aglycones of the saponins of
P. vulgaris
root are identical to those found
in the roots of
P. elatior
.
An unspecified saponin mixture from
Primula veris
exhibited activity against influenza (A
2
/Japan
305) virus, producing 89% inhibition at a concentration of 6.2 µg/ml (Rao et al. 1974; Büechi 1996).
Further
in vitro
experiments:
A hexane extract (50 µg/ml) of
Primula veris
root inhibited COX (cyclooxygenase)-1 and COX-2 by
54 % and 66 % respectively (Lohmann et al. 2000).
Oswiecimska et al. (1975) described antimitotic activity of saponin fractions and extracts from
Primulae radix and other herbal substances by means of the Allium test.
Herre (1937) published some data in rats concerning diuretic properties of
Primula officinalis
(=
Primula veris
), but there are no more recent investigations which endorse these findings.
In vivo
experiments
Experiments relevant for the proposed indications:
EMA 2010
10/11
and relevant constituents thereof on the basis of long-standing use and experience
In vivo
studies (rabbit) on pharmacological/toxicological effects of extracts from Primula flower
showed a significant increase in the production of bronchial secretion at the concentrations tested
(Chibanzuga et al.
1984)). The observed effect was in the range as secretory effects obtained with the
reference substances bromhexin and acetylcysteine which were also tested.
An undefined mixture of saponins from Primula root, at a concentration of 1:10,000, increased the
ciliary activity of throat epithelium of curarised frog. This effect was explained by a reduced mucus
surface tension. The ciliary activity was less at a concentration of 1:6,000 and ceased at 1:3,000 due to
toxic effects (Vogel 1963).
Further
in vivo
experiments:
An unspecified saponin of Primula root, administered parenterally, inhibited the growth of Walker
carcinoma in rats with an ED50 of 40 mg/kg (Tschesche & Wulff 1973). However, considering the
LD50 of 70 mg/kg this dose was too toxic and therefore less significant for practical application.
Sufka et al. (2001) tested herbal extracts for their anxiolytic properties in the chick social separation-
stress procedure. For
Primula veris
(plant part not mentioned) no sedative effects were observed and
no alteration of stress responses could be detected.
4 CLINICAL STUDIES
Clinical studies with preparations containing solely Primula flower do not exist.
The data generated in clinical trials with the special preparation Sinupret
®
cannot be included, because
the contribution of the Primula flower extract to the overall-activity cannot be estimated.
5
PHARMACOKINETIC PROPERTIES
No specific data are available on the pharmacokinetics of Primula flower saponins. In general,
saponins are poorly absorbed by the body (Hostettman & Marston 1995). Usually glycosidic bonds are
easily cleaved by enzymes of the gastrointestinal tract. The amount of absorption depends on the
galenic form of the preparation (Hänsel & Sticher 2007).
6
ASSESSOR’S OVERALL CONCLUSIONS
The expectorant effects of Primula flower preparations have long been recognised empirically; the
respective uses are made plausible by pharmacological data (level of evidence 4). Controlled clinical
studies are lacking.
In conclusion, Primula flower preparations can be regarded as traditional herbal medicinal products.
EMA 2010
11/11
Source: European Medicines Agency
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