will be received on this assessment report. The publication of this
draft
assessment report has been
agreed to facilitate the understanding by Interested Parties of the assessment that has been carried
out so far and led to the preparation of the draft monograph.
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 2/23
Table of contents
Table of contents
................................................................................................................... 3
1. Introduction....................................................................................................................... 4
1.3. Search and assessment methodology.................................................................. 1
3
2. Historical data on medicinal use ...................................................................................... 13
2.1. Information on period of medicinal use in the Community ...................................... 1
3
preparations and indications..................................................................................... 1
4
3. Non-Clinical Data ............................................................................................................. 16
preparation(s) and relevant constituents thereof ......................................................... 1
6
preparation(s) and relevant constituents thereof ......................................................... 1
9
preparation(s) and constituents thereof ..................................................................... 1
9
3.4. Overall conclusions on non-clinical data............................................................... 2
0
4. Clinical Data ..................................................................................................................... 21
4.1. Clinical Pharmacology ....................................................................................... 2
1
including data on relevant constituents ...................................................................... 2
1
including data on relevant constituents ...................................................................... 2
1
4.2. Clinical Efficacy ................................................................................................ 2
1
4.2.1. Dose response studies.................................................................................... 2
1
4.2.2. Clinical studies (case studies and clinical trials).................................................. 2
1
4.2.3. Clinical studies in special populations (e.g. elderly and children)........................... 2
1
4.3. Overall conclusions on clinical pharmacology and efficacy ...................................... 2
2
5. Clinical Safety/Pharmacovigilance................................................................................... 22
5.1. Overview of toxicological/safety data from clinical trials in humans.......................... 2
2
5.2. Patient exposure .............................................................................................. 2
2
5.3. Adverse events and serious adverse events and deaths ......................................... 2
2
5.4. Laboratory findings .......................................................................................... 2
2
5.5. Safety in special populations and situations ......................................................... 2
2
5.6. Overall conclusions on clinical safety ................................................................... 2
3
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 3/23
1.
Introduction
1.1.
Description of the herbal substance(s), herbal preparation(s) or
combinations thereof
Herbal substance(s)
In the Ph. Eur. monograph ref. 01/2008:1306, cough grass rhizome (Graminis rhizoma) is defined as
the whole or cut, washed and dried rhizome of
Agropyron repens
(L.) Beauv. (
Elymus repens
(L.)
Gould); the adventitious roots are removed (Ph. Eur. 2008).
Couch grass rhizome is known under the following common names:
English:
Scutch, Twitch grass root, Quack grass root, Triticum;
German:
Queckenwurzelstock, Laufqueckenwurzel, Schließgraswurzel, Graswurzel, Kriechwurzel;
French:
Rhizome de chiendent, Chiendent rampant;
Spanish:
Rizoma de grama de las boticas, Rizoma de grama del Norteo grama oficinal.
Polish:
Kłącze perzu
Other names:
Agropyron, Dogs Grass, Grama, Graminis Rhizoma, Juolavehnänjuurakko, Kvickrot,
Pýrový oddenek, Tarackbúza-gyökértörzs, Triticum, Twitch, Varpučių šakniastiebiai and Пырей
Ползучий
The herbal substance can also be defined as the whole or cut, washed and dried rhizomes and short
pieces of stem of
Agropyron repens
(L.) P. Beauv. (synonyms:
Agropyron caesium
J.U.C. Presl.,
Bromus glaber
Scop.,
Elymus repens
L.,
Elymus dumetorium
Hoffm.,
Elytrygia repens
Desv. ex Nevski,
Triticum arundinaceum
Poulsen ex Fries,
Triticum repens
L.,
Triticum sepitum
Thuill.), Poaceae (Hagers
Handbuch 1992).
The shiny yellowish, light brown or yellowish brown rhizome and stem pieces are hollow, longitudinally
furrowed and about 2-3 mm thick. At the unthickened nodes are the remains of very thin, more or less
branched roots and fiber-like scales. The taste is bland and slightly sweet (Wichtl 1994).
Couch grass is widely distributed weed throughout the Northern hemisphere. The material of
commerce is imported from Eastern and South-Eastern European countries.
Constituents:
Couch grass contains 3-8% triticin (similar to inulin), which yields fructose upon hydrolysis. The drug
also contains 3-4% fructose, 2-3% sugar alcohols (mannitol, inositol). Presence of agropyrene has
been disputed. Furthermore small amounts of vanillin monoglucoside, vanillic acid, phenolic carboxylic
acids, hydroxycinnamic acid alkyl ester, silicic acid and silicates are present. Small amounts of
anthraquinones were also detected (Steinegger 1972, Hoppe 1958, Hagers Handbuch 1949, Karsten
1956, Jaretzky 1937, Claus 1956, Wallis 1955, Hagers Handbuch 1992, Hiller 1999, Bruneton 1999,
Newall 1996, Borkowski 1952; 1974, Koetter 1993 and Mueller 1999).
Carbohydrates
: The rhizome is free of starch.
Polysaccharides
:
The active substances of the aqueous extract of couch grass rhizome consisted of:
polysacharide fraction (45.3
0.3%), flavonoids (0.96
0.03%), tannins (4.9
0.4%). Polysaccharides
were separated by fractional extraction for: monosaccharides-glucose, D-fructose, rhamnose; pectins
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 4/23
and hemicelluloses A and B (Petrova
et al.
2009, Steinegger and Hänsel 1972). About 10% mucilage
and possibly saponins occur (haemolytic activity is detectable) (Steinegger 1972, Haensel 1992).
Sugar alcohols
: Inositol, mannitol (2-3%) (Stoop
et al.
1996).
Fructans
: (storage carbohydrates) 3-10% (Arni and Percival 1951, Bruneton 1999, Biggs and Hancock
2001, Steinegger and Hänsel 1972).
Triticin
: Laevorotatory carbohydrate high-branched out polysaccharide resembling inulin (3-18%)
(Steinegger and Hänsel 1972).
Free fatty acids
: 36% (particularly palmitic acid).
Phenol compounds
: P-hydroxybenzoic, vanilic and p-coumaric acids (Whitehead
et al.
1982).
Chlorogenic acid, p-hydroxycinnamic acids (Petrova
et al.
2009). P-hydroxycinnamic acid esters: (E)-
and (Z)-p-coumaric acid hexadecyl ester and (E)-and (Z)-p-coumaric acid-16-hydroxyhexadecylester
(Koetter
et al.
1993) and bis-(E)- and bis-(Z)-diesters of analogous structure (Koetter
et al.
1994).
Presence of agropyrene has been disputed.
Essential oil:
(0.01-0.02%): 25% monoterpens (carvacrol, carvon, trans-anethole, thymol and
menthol, among others), 0.85% sesquiterpenes(Boesel and Schilcher 1989) and other compounds
including 2-hexyl-3-methyl-maleic acid anhydride.
Flavonoids
: Tricin, rutin, baicaleine, hyperoside (Petrova
et al.
2009).
Anthraquinones
: Sum of anthraquinones (0.2-0.7 mg/kg): emodin (0.06-0.2 mg/kg),
chrysophanol 0.05-0.2 mg/kg, physcion 0.08-0.3 mg/kg (Mueller
et al.
1999).
Steroids
: oestrogen, androstenone, progesterone and androgens in trace amounts (Simons and
Grinwich 1989).
Lectins
: which can be found in the seedlings and leaves of
Agropyron repens
may also be present in
the rhizome. Purified leaf lectin (ARLL) corresponds to a M
r
of 19,500 compared to M
r
of 18,000 for the
embrio lectins (AREL). ARLL polypeptide is slightly larger than cereal embrio lectins. They also exhibit
different agglutination properties: ARLL is GalNAc-specific and agglutinates preferentially red blood
cells of group A, since AREL is GlcNAc-specific and has no blood group specificity at all (Cammue
et al.
1985).
Saponins
: presence has not been confirmed.
Microelements
: Concentrations of an iron and zinc in infusions prepared from raw
Agropyron repens
rhizomes was estimated in the range of 3.78-6.84
g/g and 7.12-10.80
g/g respectively (Arceusz
et
al.
2009).
Silicic acid and silicates:
Total Si level (%) in rhizomes of
Agropyron repens
at various stages of its
vegetation between June and October increased in the range of 0.37-0.43. The maximum
concentrations in decoction were obtained after boiling 3 g of rhizomes in a glass of water for 2 hours
under a cover. One glass of decoction contains 2.6 mg of assimilable silicon equivalent to 5.6 mg of
Si02 (Pasławska and Piekos 1976).
Herbal preparation(s)
Comminuted herbal substance
Liquid extract (1:1) extraction solvent: ethanol 20-25% V/V
Tincture (1:5) extraction solvent: ethanol 40% V/V
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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Combinations of herbal substance(s) and/or herbal preparation(s) including a description of
vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products
assessed, where applicable.
The herbal substance is also available in combination products. Main plants used in combination are:
Achillea millefolium, Allium cepa , Althea officinalis, Betula pendula, Calendula officinalis, Carum carvi,
Cichorium intybus, Cynara scolymus, Equisetum arvense, Frangula alnus, Levisticum officinale, Linum
usitassimum, Matricaria chamomilla, Mentha piperita, Petroselinum crispum, Phaseolus vulgaris,
Polygonum avicularis, Rheum officinale, Ribis nigrum, Sambuccus nigra, Silybum marianum, Solidago
virgaurea, Taraxacum officinalis, Tilia cordata, Trigonella foenugraecum, Urtica dioica
and
Viola
tricoloris
.
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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1.2.
Information about products on the market in the Member States
Estonia:
There are no products containing
Agropyron repens
rhizomes as a single active ingredient or in
combination.
Germany:
Traditional Use*
Preparations (kind of extract, extraction solvent, DER)
Liquid extract (1:1), extraction solvent: ethanol 20% V/V
Since when are the preparations on the market?
At least since 2007
Pharmaceutical form (Standard Terms)
Oral liquid
Posology (Route of administration in Standard Terms + daily dosage)
For oral use in adults > 18 years: 3 times daily 3 ml containing 100% of liquid extract
Indications
Traditionally used to increase the amount of urine to achieve flushing of the urinary tract as an
adjuvant in minor urinary complaints.
Risks (adverse drug effects, literature)
Use in children and adolescents below the age of 18 years and during pregnancy and lactation is not
recommended because of insufficient data.
Is the Herbal Substance on the market?
Yes No
Status
Authorised products Registered products Food supplements
Were pharmacovigilance actions taken on medicinal products containing the herbal substance?
Yes No.
Combination products
In Germany, there is 1 authorised combination product.
Average number of combination substances: 2-3 3-5 >5
Additional comments: German Standard Marketing Authorisations
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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Single active ingredient: 1
Combination products: 7
All of them are herbal teas.
*For the sake of completeness, all preparations for which marketing authorisations for traditional use
have been granted (with reference to former German national regulations) are mentioned, regardless
of the fact that some of them are not in accordance with current Community law (as defined in
Directive 2004/24/EC). Traditional preparations were authorised in 10-50% of well-established use
doses when in parallel the same preparations were authorised under well-established use.
Latvia:
One authorised medicinal combination products containing
Agropyron repens
rhizome (extractum
Agropyri rhizome) is available on the Latvian market, as a paste for oral use, in cases of urinary tract
infections and nephrolithiasis.
There are also products with
Agropyron repens
are on the Latvian market as food supplements (one
product with
A. repens
as single ingredient and a few combination products).
Poland:
Traditional Use
Preparations (kind of extract, extraction solvent, DER)
Herbal substance (herbal tea), single ingredient
Since when are the preparations on the market?
At least since 1994
Pharmaceutical form (Standard Terms)
Herbal tea
Posology (Route of administration in Standard Terms + daily dosage)
1.5-3.0 g of comminuted herbal substance in 200 ml of boiling water for 15 min, 4 times daily
Indications
Traditionally in troubles with urination to increase the amount of urine and to achieve flushing of the
urinary tract as an adjuvant in minor urinary complaints.
Risks (adverse drug effects, literature)
Use in children and adolescents below the age of 18 years and during pregnancy and lactation is not
recommended because of insufficient data.
Contraindications
Do not use in oedema in renal/cardiac insufficiency.
Is the Herbal Substance on the market?
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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Yes No
Status
Authorised products Registered products Food supplements
Were pharmacovigilance actions taken on medicinal products containing the herbal substance?
Yes No
Combination products
Average number of combination substances: 2-3 3-5 >5
a) Chopped herbs:
Graminis rhizome, Equiseti herba, Taraxaci herba, Taraxaci radix
and
Frangulae
cortex.
b) Chopped herbs:
Frangulae cortex, Graminis rhizome, Carvi fructus
and
Lini semen.
c) Chopped herbs:
Graminis rhizome, Violae tricoloris herba, Cichorii radix, Urtice folium, Phaseoli
pericarpium
and
Rhei radix.
d) Chopped herbs:
Silybi mariani fructus, Cynarae herba, Taraxaci radix, Urticae folium, Calendulae
anthodium
and
Graminis rhizoma
e) Chopped herbs:
Menthae piperitae folium, Graminis rhizoma, Matricariae flos, Taraxaci radix cum
herba, Carvi fructus
and
Frangulae cortex.
f) Paste: Extractum compositum (1:1.3-1.6) ex:
Graminis rhizomate, Allii cepae squama, Betulae folio,
Foenugraeci semen, Petroselini radix, Solidaginis herba, Equiseti herba, Levistici radix
and
Polygoni
avicularis herba
; extraction solvent – ethanol 45% (V/V).
g) Extractum compositum fluidum (1:1) ex:
Phaseoli pericarpio, Betulae folio, Graminis rhizomate,
Rubi fruticose folio
and
rose fructus;
extraction solvent – ethanol 70% (V/V).
Since when are the preparations on the market? -
a) 8 years
b) 5 years
c) 6 years
d) 21 years
e) 17 years
f) 49 years (since 1961)
g) 8 years
Pharmaceutical form (Standard Terms)
a) Herbal tea (comminuted herbal substance)
b) Herbal tea (comminuted herbal substance)
c) Herbal tea (comminuted herbal substance)
d) Herbal tea (comminuted herbal substance)
e) Herbal tea (comminuted herbal substance)
f) Oral paste (dry extract)
g) Oral liquid (liquid extract)
Posology (Route of administration in Standard Terms + daily dosage)
a) Oral use: 2 g (0.7 g of
Graminis rhizoma
) 1-2 times daily
b) Oral use: 1 g (0.25 g of
Graminis rhizoma
) daily
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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c) Oral use: 2 g (0.6 g of
Graminis rhizoma
) 2-3 times daily
d) Oral use: 5-10 g (0.375-0.75 g of
Graminis rhizoma
) 2-3 times daily
e) Oral use: 5 g (1 g of
Graminis rhizoma
) 1-3 times daily
f) Oral use: 5 g (3.36 g of extract corresponds to 0.42 g of
Graminis rhizoma
) 3-4 times daily
g) Oral use: 5 ml (0.92 g of
Graminis rhizoma
) up to 4 times daily
What are the main combination substances?
Achillea millefolium, Allium cepa, Althea officinalis, Betula pendula, Calendula officinalis, Carum carvi,
Cichorium intybus, Cynara scolymus, Equisetum arvense, Frangula alnus, Levisticum officinale, Linum
usitassimum, Matricaria chamomilla, Mentha piperita, Petroselinum crispum, Phaseolus vulgaris,
Polygonum avicularis, Rheum officinale, Ribis nigrum, Sambuccus nigra, Silybum marianum, Solidago
virgaurea, Taraxacum officinalis, Tilia cordata, Trigonella foenugraecum, Urtica dioica
and
Viola
tricoloris.
Other information on relevant combination products: herbal substance is included in compositions:
Species laxantes
and
Species metabolicae.
Additional comments:
There are 7 single active ingredient products and 7 combination products containing couch grass on
the Polish market.
Portugal:
There are no authorised products (single or in combination) with
Agropyron repens
. Products with
Agropyron repens
could be on the market as food supplements.
Slovak Republic:
There are no registered medicinal products containing
Agropyron repens
L. as a single ingredient or in
combination.
Sweden:
There are no products containing Agropyron.
United Kingdom:
Traditional Use
Preparations (kind of extract, extraction solvent, DER)
1. blended chopped herb
2. dry extract (5:1)
3. liquid extract (1:1), extraction solvent: ethanol 21%
Since when are the preparations on the market?
Since 1968
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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Pharmaceutical form (Standard Terms)
1. herbal substance
2. dry extract
3. liquid extract
Posology (Route of administration in Standard Terms + daily dosage)
1.
6 g infused in 0.5 l of boiling water and taken daily in portions when cool enough.
2.
two tablets 3 times daily (containing 12 mg of
Agropyron repens
dry extract ) after meals.
3.
one 5 ml teaspoonful three times daily containing 0.875 ml of liquid extract of couch grass.
Indications
1.
A herbal remedy traditionally used for short term symptomatic relief of urinary and bladder
discomfort and associated backache.
2.
A herbal remedy traditionally used for symptomatic relief of urinary or bladder discomfort.
3.
A traditional herbal remedy for the symptomatic relief of urinary or bladder discomfort.
Risks (adverse drug effects, literature)
Adults and elderly only. Children: not recommended. Avoid in early pregnancy and lactation.
Is the Herbal Substance on the market?
Yes No
Status
Authorised products Registered products Food supplements
Were pharmacovigilance actions taken on medicinal products containing the herbal substance?
Yes No
Combination products
Average number of combination substances: 2-3 3-5 >5
What are the main combination substances?
Barosma betulina,
Asperugo procumbens
,
Agropyron repens
,
Equisetum arvense, Uva ursi, Cassia
angustifolium, Capsella bursa-pastoris, Althea officinalis
and
Juniperus communis.
Regulatory status overview
Member State Regulatory Status
Comments (not
mandatory field)
Austria
MA
TRAD
Other TRAD
Other Specify:
Belgium
MA
TRAD
Other TRAD
Other Specify:
Bulgaria
MA
TRAD
Other TRAD
Other Specify:
Cyprus
MA
TRAD
Other TRAD
Other Specify:
Czech Republic
MA
TRAD
Other TRAD
Other Specify:
Denmark
MA
TRAD
Other TRAD
Other Specify:
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 11/23
Member State Regulatory Status
Comments (not
mandatory field)
Estonia
MA
TRAD
Other TRAD
Other Specify:
Not present
Finland
MA
TRAD
Other TRAD
Other Specify:
France
MA
TRAD
Other TRAD
Other Specify:
Germany
MA
TRAD
Other TRAD
Other Specify:
The herbal substance is also
available in combination
products
Greece
MA
TRAD
Other TRAD
Other Specify:
Hungary
MA
TRAD
Other TRAD
Other Specify:
Iceland
MA
TRAD
Other TRAD
Other Specify:
Ireland
MA
TRAD
Other TRAD
Other Specify:
Italy
MA
TRAD
Other TRAD
Other Specify:
Latvia
MA
TRAD
Other TRAD
Other Specify:
The herbal substance is
available in combination
product
Liechtenstein
MA
TRAD
Other TRAD
Other Specify:
Lithuania
MA
TRAD
Other TRAD
Other Specify:
Luxemburg
MA
TRAD
Other TRAD
Other Specify:
Malta
MA
TRAD
Other TRAD
Other Specify:
The Netherlands
MA
TRAD
Other TRAD
Other Specify:
Norway
MA
TRAD
Other TRAD
Other Specify:
Poland
MA
TRAD
Other TRAD
Other Specify:
The herbal substance is also
available in combination
products
Portugal
MA
TRAD
Other TRAD
Other Specify:
Not present
Romania
MA
TRAD
Other TRAD
Other Specify:
Slovak Republic
MA
TRAD
Other TRAD
Other Specify:
Not present
Slovenia
MA
TRAD
Other TRAD
Other Specify:
Spain
MA
TRAD
Other TRAD
Other Specify:
Sweden
MA
TRAD
Other TRAD
Other Specify:
Not present
United Kingdom
MA
TRAD
Other TRAD
Other Specify:
The herbal substance is
available in combination
products
MA: Marketing Authorisation
TRAD: Traditional Use Registration
Other TRAD: Other national Traditional systems of registration
Other: If known, it should be specified or otherwise add ’Not Known’
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the
products in the MSs concerned.
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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1.3.
Search and assessment methodology
The following databases were assessed:
PubMed, until August 2010
The Cochrane Library, August 2010;
OvidMedline, August 2010;
Embase, August 2010
Search terms:
Agropyron repens
,
Elymus repens, Elytrygia repens, Triticum repens, Graminis rhizome
,
Couch grass and Quack grass
2.
Historical data on medicinal use
2.1.
Information on period of medicinal use in the Community
Couch grass rhizome has been traditionally used as diuretic, mainly in compositions (Borkowski 1952;
1974, Claus 1956, Frohne 1994, Hiller and Melzig 1999, Oppermann 1995 and Receptariusz Zielarski
1963; 1967).
Agropyron repens
has been traditionally used in treatment since ancient times. Its name was
mentioned in the publications of Dioskurides, Plinius, Tabermontanus-Bauhinus 1588 and Matthiolus
1626 according to Madaus “Lehrbuch der Biologischen Heilmittel”, 1938.
The herbal substance is mentioned in several well known handbooks such as Barnes
et al.
2002,
Bradley 2006, Duke’s Handbook of Medicinal Herbs 2002, ESCOP Monographs 2009,
German Commission E Monograph 1990, Hagers Handbuch 1949; 1992, Hiller and Melzig 1999,
Hoppe 1958, Madaus 1938, Martindale 2009, Jaretzky 1937, Karsten 1956, Newall
et al.
1996,
PDR for Herbal Medicines 2000; 2004, Schulz
et al.
1998, Wallis 1955 and Wichtl 1994; 2002.
In Greece according to ethnobotanical tradition,
Agropyron repens
is used not only in urinary tract
disorders (cystitis, kidney stones, prostate enlargement) but also in gastrointestinal problems
(gallstones), in arthritis and rheumatism and to reduce increased cholesterol levels
(Hanlidou
et al.
2004).
In Bulgaria and Italy, couch grass rhizomes are traditionally used as diuretic and laxatives (Leporatti
and Ivancheva 2003). It is also used as a diuretic by ethnic Albanian communities living in the Vulture
area in Southern Italy (Pieroni
et al.
2002).
In Bosnia and Herzegovina, traditional use of couch grass as diuretic and in rheumatic complaint is
described (Redžić 2007).
Agropyron repens
(L.). rhizomes, dried, ground and made into flour used to make bread or thick soup
in famine conditions were used in Poland until the mid-20th century and might have been used to
make beer until the 18th century (Łuczaj and Szymański 2007, Łuczaj 2008).
The pulverised rhizomes of
Agropyron repens
(2-3 g 3 times daily for 10-12 days) were used in order
to reduce irritable condition of bladder and to promote urination (Ballabh
et al.
2008).
Agropyron repens
is also used in ethnoveterinary medicine to treat endoparasites and gastrointestinal
problems in Italy and in Canada (Lans
et al.
2007, Viegi
et al.
2003).
Overall conclusion on the traditional medicinal use
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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Preparations from
Agropyron repens
rhizome have long been used for diuresis stimulation. The
traditional medicinal use is made plausible by pharmacological data.
2.2.
Information on traditional/current indications and specified
substances/preparations
See section 2.3.
2.3.
Specified strength/posology/route of administration/duration of use
for relevant preparations and indications
British
Herbal Compendium (Bradley, 2006)
Traditionally used in inflammatory ailments and infections of the urinary tract, cystitis, urethritis,
prostatitis and irritable bladder. It has been also used in the treatment of renal stones, gout and
rheumatic disorders and chronic skin complaints.
Daily dose: dried rhizome, 4-8 g as herbal tea; liquid extract 1:1 in 25% alcohol, 4-8 ml;
tincture 1:5 in 40% alcohol, 5-15 ml.
Duration of use: no information
British Herbal Pharmacopoeia (1971)
Action: diuretic
Indications: Cystitis, urethritis, prostatitis, benign prostatic hypertrophy, renal calculus, lithuria
Combination used: May be combined with Agathosma in cystitis, and with Hydrangea in prostatic
enlargement.
Specific indications: Cystitis with irritation or inflammation of the urinary tract
Preparations and dosage: Dried rhizome. Dose 4-8 ml. Tincture 1:5 in 40% alcohol. Dose 5-15 ml.
3 times daily.
German Commission E Monograph (Bundesanzeiger No. 22a, 01.02.1990)
Graminis rhizoma (Agropyri rhizoma)
Irrigation therapy for inflammatory diseases of urinary tract and for the prevention of kidney gravel.
Daily dose: 6-9 g of comminuted herb or equivalent preparations.
Duration of use: no information.
ESCOP Monograph (Supplement 2009)
Graminis rhizoma - couch grass rhizome
Indications: Irritable bladder and other urinary tract disorders. Efficacy is plausible on the basis of
tradition and long-standing use.
Dosage: Oral administration
Adults and children over 12 years: Herbal substance: 5-10 g as infusion daily
Fluid extract (1:1, 20-25% ethanol V/V), 2-4 times daily
Tincture (1:5, ethanol 40% V/V), 5-15 ml 3 times daily
Duration of use: No restriction. If symptoms persist or worsen, medical advice should be sought.
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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Hager’s Handbuch (Hänsel
et al.
1992)
Irrigation therapy for inflammatory diseases of urinary tract and for the prevention of kidney gravel.
Other traditional indications: Rheumatic complaints, diabetic nutrition (fructosans)
Dosage:
Tea: Agropyri repentis rhizoma. 6-9 g, of comminuted herbal substance (according to Commission E);
either 20-40 g (Standardzulassungen für Fertigarzneimittel, Nr. 1169.99.99, 1988) or 12-24 g (BHP
1983) as herbal tea daily.
Tea preparation: Pour boiling water over the comminuted herbal substance and strain after 10
minutes.
Fluid extracts (1:1): 4-8 ml, 3 times daily
Tincture (1:5): 5-15 ml, 3 times daily
Warnings: Do not use in oedema in renal/cardiac insufficiency.
Herbal Drugs and Phytopharmaceuticals (Wichtl, 2002)
Diuretic in cases of bladder inflammation and bladder and kidney stones. According to folk tradition as
a cough remedy to alleviate the irritation in bronchial catarrh and in rheumatic disorders, gout and
chronic skin conditions.
Dosage: 5-20 g of the chopped drug in boiling water, after 5-10 minutes passed through a tea strainer.
It is also recommended to put the herbal substance in cold water and slowly bring it to the boil
(1 teaspoon = ca. 1.5 g). Unless otherwise prescribed, a cup is drunk up to 4 times daily.
Lehrbuch der Biologischen Heilmittel (Madaus, 1938)
Indications: urinary tract complaints, renal stones and rheumatic ailments.
Dosage: Agropyri rhizoma 14 g (4 teaspoons) fresh herbal tea daily; 1 g comminuted herbal substance
3 times daily; 1 teaspoon of the fresh powdered herbal substance 4 times daily.
Maximal dose is not described.
Duration of use: no information.
Martindale 2009
Agropyron repens
is a mild diuretic that has been used in herbal medicine in the treatment of urinary-
tract disorders.
Dose: no information.
Duration of use: no information.
PDR for Herbal Medicines (2000, 2004)
The medicinal part is the rhizome collected in spring and autumn.
Indicated in infections of the urinary tract and kidney and bladder stones.
Comminuted herbal substance: 3-10 g/day. (1 teaspoon corresponds to 3 g of drug).
Tea: 3-10 g in 1 cup (250 ml) of boiling water; strain after 10 minutes. Drink fresh several times a
day.
Liquid extract: 4 to 8 ml, 3 times daily.
Tincture: 5 to 15 ml, 3 times daily.
Storage: the drug must be kept in sealed containers, protected from light and moisture.
Duration of use: no information.
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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3.
Non-Clinical Data
3.1.
Overview of available pharmacological data regarding the herbal
substance(s), herbal preparation(s) and relevant constituents thereof
In vivo
experiments
Diuretic activity
Diuretic activity was shown by Racz-Kotilla and Mozes (1974) in rats after oral administration of an
aqueous extract (1% macerate). After receiving 50 ml/kg body weight, diuretic index increased by
1.42 compared to control rats receiving water only.
Stronger diuretic effect (index of 1.62) was observed after i.p. administration of an equivalent dose of
the dry hydroalcoholic extract dissolved in water corresponding to 10% of dried rhizome at 5 ml/kg
body weight.
Effects on the calcium oxalate urolithiasis urinary risk factors
The effects on the calcium oxalate urolithiasis urinary risk factors of administration of
Agropyron
repens
L. (
Gramineae
), in herb infusion form, combined with different diets (standard, high glucidic,
high protein) have been studied using Wistar rats. From this study, it is deduced that administration of
the
Agropyron repens
infusion cannot be associated to any positive effects on the main urolithiasis risk
factors.
According to Grases 1995, some significant diuretic effects (p<0.005) with infusion of
Agropyron
repens
herbal tea were registered with calciuria increased (p<0.005) and magnesiuria decreased
(p<0.005) when standard diet was used. Moreover, citratruria decreased when couch grass infusion
was associated with a high glucidic diet (Table 1). In conclusion, the authors concluded that the
conditional diuretic effect of couch grass infusion cannot be attributed to the diet.
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 16/23
Table 1
Volume consumed, diuresis and urinary biochemical parameters for different diets, without herb (control) with
Agropyron repens
infusion
(according to Grases 1995)
Volume
consumed
(ml)
Diuresis
pH
Ca
Mg
Phos (mg/l)
Creat
Cit
Standard diet
Control
37.0
3.5
17.0
2.3
7.8
0.5
187
76
572
82
4384
972
56
87
3787
677
Agropyron repens
34.2
8.4
21.7
4.7
**
7.4
0.6
277
77
**
448
125
**
4966
856
768
171
3151
980
High protein diet
Control
34.3
5.0
27.9
4.5
6.5
0.8
191
61
258
42
7176
609
520
51
176
57
Agropyron repens
33.8
9.0
24.6
4.0
5.9
0.1
*
218
54
163
20
***
12120
1792
***
571
101
180
43
High glucidic diet
Control
29.8
7.9
21.5
8.3
5.8
0.3
130
61
228
89
5225
1197
831
272
195
59
Agropyron repens
27.5
8.4
22.5
6.9
5.9
0.5
178
66
222
51
4845
1348
590
116
**
118
78
*
The values are expressed as mean
SD of 12 animals; *p<0.01, **p<0.005, *** p<0.0005
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
Page 17/23
EMA/HMPC/563395/2010
Anti-inflammatory activity
Moderate inhibition of carrageenin foot oedema of the rat hind-paw (14%) was found after oral
administration of 80% ethanol extract of rhizomes of
Agropyron repens
(100 mg/kg) compared to
indometacin effects (45% of inhibition) at 5 mg/kg (Mascolo
et al.
1987).
In the animal model of allergic contact dermatitis induced topically in rats after depilation with two
applications of 0.1 ml of 5% alcoholic solution 2.4-dinitrochlorobenzene (DNCB), the cream containing
dry couch grass extract was tested. After DNCB use the skin was hyperemic, edematous with serous
purulent changes and itching. Couch grass extract cream was applied 3 days after the beginning of
sensitization. Evaluation of the anti-inflammatory activity of the cream was monitored 4, 6 and 10 days
after the experiment started. Plasma lipid peroxidation parameters: malondialdehyde (MDA), diene
conjugates (DC) and catalase activity were registered. After 2 days of treatment with couch grass
cream (4th day of experiment) decrease of erythema, edema and infiltration was seen. On the 6th day
of experiment the skin of rats treated with cream containing couch grass returned to baseline values
with reduction of edema and erythema. The visual symptoms of recovery of the control untreated rats
were seen at 10 days. The activity of the antioxidant enzyme catalase increased by 30% at the 4th day
and by 15% at the 6th day of experiment compared to the control. Biochemical parameters showed, at
the end of the experiment on the 10th day, control levels of MDA and increased the activity of
catalase, a major antioxidant defense enzyme. The couch grass cream application resulted in
quickening the recovery by 4-5 days as compared with untreated control animals. The anti-
inflammatory effects of the couch grass cream were comparable to the standard glucocorticoid cream
activity (Petrova
et al.
2009).
Effect on lipid metabolism
The effect of single and repeated oral administration of the lyophilized aqueous extract of rhizomes of
Agropyron repens
(20 mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats
was tested by Maghrani
et al.
. In normal rats, the aqueous extract induced a significant decrease in
the plasma triglycerides concentrations 4 days and 1 week after repeated oral administration. This
reduction was abolished 2 weeks after once daily repeated oral administration. A significant decrease
of plasma cholesterol levels was observed only 1 week after repeated oral administration. In diabetic
rats treatment caused a significant decrease in plasma cholesterol after single and repeated oral
administration. A strong decrease in cholesterol levels was observed 6 hours after a single oral
administration of the extract. Four days after repeated oral administration of the extract, the plasma
cholesterol level was significantly decreased and remained still diminished after 2 weeks. The repeated
oral administration of the aqueous extract of
Agropyron repens
rhizomes caused a significant decrease
in body weight 2 weeks after oral treatment. In severely hyperglycaemic rats
Agropyron repens
extract
treatment induced reduction of lipid levels and body weight (Maghrani
et al.
2004).
Antidiabetic effects
The hypoglycaemic effect of an aqueous extract of
Agropyron repens
was investigated in normal and
streptozotocin-induced diabetic rats. After a single oral administration (20 mg/kg) of the daily prepared
and lyophilized aqueous extract (1 g/100 ml of water) a significant decrease in blood glucose levels in
diabetic rats was observed. The blood glucose levels were normalized after 2 weeks of daily oral
administration of 20 mg/kg of the extract. Significant reduction of blood glucose levels were also
noticed in normal rats after acute and chronic treatment. No changes were observed in basal plasma
insulin concentrations after treatment in either normal or diabetic rats. The authors remarked that
traditionally an aqueous extract of
Agropyron repens
rhizoma is used in Maroc as antidiabetic
treatment (Eddouks
et al.
2005; 2007).
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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Effect on motility
Experiments were performed on rota-rod with male mice (20-30 g body weight). Each group of mice
(N=30) received either orally or i.p. 10% infusum of Rhizoma graminis (either 40 or 80 mg/
20 g mouse). Control mice received orally or i.p. 0.9% NaCl solution. Motility tests were performed
after 2 and 8 hours after administration of the tested solutions. Other groups of mice received
equivalent doses of
Valerianae radix
or
Radix Helenae infusum
. All tested plant products induced
comparable significant dose-dependent inhibition of motility. Similar comparable effects were obtained
with use of the ether extracts of plants tested. The unspecific sedative effects of assayed plants with
an unknown mechanism of action are discussed by the authors (Kiesewetter and Müller 1958).
3.2.
Overview of available pharmacokinetic data regarding the herbal
substance(s), herbal preparation(s) and relevant constituents thereof
No data are available concerning couch grass rhizome pharmacokinetics; the complex phytochemical
composition is acknowledged.
Interactions -
No data available
Due to lack of data on pharmacokinetics of couch grass rhizome constituents, no relevant conclusions
can be drawn.
3.3.
Overview of available toxicological data regarding the herbal
substance(s)/herbal preparation(s) and constituents thereof
The allelopathic influence of
Agropyron repens
on higher plants is described in numerous publications
(Hagin and Bobnick 1991, Henderson and Triebskorn 2002, Friebe
et al.
1995, Korhammer and
Haslinger 1994, Sánchez–Moreiras
et al.
2004 and Weston
et al.
1987) but it is not relevant for safety
of therapeutic use of the herbal substance and herbal preparations.
The phenolic glycoside fraction extracted from the dried quack grass roots is responsible not only for
the allelopathic effect on seedlings of forage legumes but also for molluscidal effects on two slug
species:
Deroceras reticulatum
(Müller 1999) and
Deroceras laeve
(Müller 1999, Hagin and Bobnick
1991). The main allelopathic substances in rhizomes of
Agropyron repens
were found to be 5-
hydroxyindole-3-acetic acid and 5-hydroxytryptophan (Hagin and Bobnick 1991, Powell and Petroski
1992).
Weston
et al.
(1987) described the phytotoxic compounds after sequential partitioning of the aqueous
extract of the quack grass shoots; the ether extract exhibited the most activity. From two flavonoid
inhibitors isolated from the ether extract, one was recognized as tricin (5,7,4’-trihydroxy-3’,5’-
dimethoxyflavone). Both tricin and compound 2 caused 50% inhibition of radicle elongation of curly
cress (
Lepidium sativum
L.) at concentration of 123.3 and 59.3
g/ml respectively. These compounds
may be released by exudation or degradation from both living and dead
Agropyron repens
shoots and
rhizomes (Toai and Linscott 1979). Similar effects were shown by Penn and Lynch (1981; 1982), who
found phytotoxic activity of both living and decaying couch rhizomes against the growth of seedlings of
barley. They have shown that the anaerobic decay can generate phytotoxic concentrations of acetic
and butyric acid.
From shoots and root exudates of 10-day old couch grass seedlings, several other phytotoxins were
isolated such as cyclic hydroxamic acids: 2,4-dihydroxy-7-methoxy-2H—1,4-benzoxazin-3-one
(DIMBOA - 0.02 mg/g), 2,4-dihydroxy-2H—1,4-benzoxazin-3-one (DIBOA – 0.5 mg/g) and the lactam
derivative 2-hydroxy-1,4-benzoxazin-3-one (HBOA). Besides maleic, aconitic and citric acids, were
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 19/23
isolated from the living intact seedlings of
Agropyron repens
vanilic acid, ferulic acid and β-
hydroxybutyric acid in the range of 10 nmol/l (Friebe
et al.
1995, Macias
et al.
2006).
In famine, couch grass was traditionally a natural source of food.
In the USA,
Agropyron repens
is listed as GRAS (Generally Recognized As Safe) and its juice is used in
several food supplements.
Genotoxicity
Schimmer
et al.
(1994) showed no mutagenic potential of the fluid extract (1:1, 20% ethanol) of the
Agropyron repens
rhizome in the Ames test with
Salmonella typhimurium
strains TA98 and TA100 with
and without S9 mix from induced rat liver microsomes with maximal dose tested of 200
/plate.
Carcinogenicity
No published data could be found on the carcinogenicity of the couch grass rhizome and couch grass
rhizome preparations.
Acute toxicity
No studies on acute toxicity have been performed with couch grass rhizome and couch grass rhizome
preparations.
Repeated dose toxicity
No studies on repeated dose toxicity have been performed with couch grass rhizome and couch grass
rhizome preparations.
Assessor’s overall conclusions on toxicology
Practically no toxicity studies on couch grass rhizome and couch grass rhizome preparations are
available in the literature.
Due to the lack of data on acute and chronic toxicity, repeated dose toxicity, carcinogenicity,
reproductive and developmental toxicity, a list entry for
Agropyron repens
rhizome cannot be
recommended.
3.4.
Overall conclusions on non-clinical data
Pharmacological activities of the rhizome support the traditional use of preparations containing
Agropyron repens
rhizome in the proposed indication in minor urinary complaints.
Toxicological data on couch grass rhizome are very limited, but neither the European tradition nor
known constituents suggest that there is potential risk associated with the couch grass use. Due to the
lack of data on acute and chronic toxicity, repeated dose toxicity, mutagenicity, carcinogenicity,
reproductive and developmental toxicity, a list entry for
Agropyron repens
cannot be recommended.
Oral administration of preparations from
Agropyron repens
rhizome can be regarded as safe at
traditionally used doses with the exception of patients with severe renal or cardiac disease e.g. renal
and heart failure. Treatment should be avoided because of possible complications due to
hypokalaemia.
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 20/23
4.
Clinical Data
4.1.
Clinical Pharmacology
4.1.1.
Overview of pharmacodynamic data regarding the herbal
substance(s)/preparation(s) including data on relevant constituents
There are no data on human pharmacodynamics.
4.1.2.
Overview of pharmacokinetic data regarding the herbal
substance(s)/preparation(s) including data on relevant constituents
There are no data on human pharmacokinetics.
4.2.
Clinical Efficacy
See below.
4.2.1.
Dose response studies
There are no specific data available on dose-response studies.
4.2.2.
Clinical studies (case studies and clinical trials)
Observational studies
Effect of fluid extract of
Agropyron repens
in urinary tract infections and irritable bladder
In the open clinical trial in 99 patients with micturition disorders (12 female and 87 male), a
20% ethanol fluid extract of
Agropyron repens
was administered for 28-31 days (60 drops 3 times
daily). The complaints of urge incontinence, dysuria, nycturia and tenesmus due to adenoma of
prostate, prostatitis and cystitis were successfully significantly reduced in 44.4-100 % of patients.
Laboratory markers of inflammation (protein, epithelia, leucocyte and erythrocyte in urine) were also
normalised. In result, 96% of patients estimated results as good or very good. Adverse effects were
not recorded (Barsom 1981).
The efficacy and tolerability of a fluid extract of couch grass in 313 patients with urinary tract
infections or irritable bladder was analysed in a multicenter open post-marketing study. The patients
with diagnosis of irritable blader, urethritis, cystitis and prostatitis were included to the test. The
patients were treated on average for 12 days with 50-60 drops of 20% fluid ethanolic extract of
Agropyron repens
. Primary efficacy criterion was the clinically relevant improvement and change of
urologic symptoms during the course of therapy: urge incontinence, painful micturition, dysuria,
pollakisuria, nycturia and tenesmus. Dependent on the underlying urologic diagnosis, between 32%
and 53% of the patients were completely free of symptoms following treatment (32% of patients with
irritable bladder, 44% with urethritis, 53% with cystitis and 42% with prostatitis) No side effects were
reported (Hautmann and Scheithe 2000).
4.2.3.
Clinical studies in special populations (e.g. elderly and children)
No information available.
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
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4.3.
Overall conclusions on clinical pharmacology and efficacy
On the basis of published data, the quality of the available studies cannot be evaluated. There are no
data available from controlled clinical studies.
Overall, the medicinal use of couch grass rhizome has to be regarded as traditional.
Administration of preparations of couch grass rhizome can be regarded as safe, especially at
therapeutic doses, concentrations and for a short time of use.
5.
Clinical Safety/Pharmacovigilance
There are no adverse effects reported from the Member States, however attention should be paid to
hypersensitivity to the active substance(s) and to other members of the Poaceae family.
5.1.
Overview of toxicological/safety data from clinical trials in humans
There are no data from clinical trials available.
5.2.
Patient exposure
None reported.
5.3.
Adverse events and serious adverse events and deaths
None reported.
5.4.
Laboratory findings
No data available.
5.5.
Safety in special populations and situations
Intrinsic (including elderly and children)/extrinsic factors
There are no reports of couch grass rhizome in children. The use of couch grass rhizome is not
recommended in children and adolescents under 18 years of age.
Use in pregnancy and lactation.
The couch grass rhizome should not be used during pregnancy and lactation.
None reported.
Drug interactions
None reported for couch grass rhizome preparations.
Effect on ability to drive or operate machinery or impairment of mental ability
None reported.
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Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 22/23
5.6.
Overall conclusions on clinical safety
There are no reports of adverse effects of
Agropyron repens
from Member States in the European
Union.
6.
Overall conclusions
The available data are sufficient to establish a Community herbal monograph on the traditional use of
couch grass rhizome. Couch grass rhizome fulfils the requirement of medicinal use for at least 30 years
(including at least 15 years within the European Union, Directive 2004/24/EC).
Indication: Traditional herbal medicinal product to increase the amount of urine to achieve flushing of
the urinary tract as an adjuvant in minor urinary complaints. The product is a traditional herbal
medicinal product for use in the specified indication exclusively based upon long-standing use.
Due to the lack of data on acute and chronic toxicity, repeated dose toxicity, carcinogenicity,
reproductive and developmental toxicity, a list entry for
Agropyron repens
cannot be recommended.
Annex
List of references
Assessment report on
Agropyron repens
(L.) P. Beauv., rhizoma
EMA/HMPC/563395/2010
Page 23/23
Source: European Medicines Agency
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