Gavez (Symphytum officinale L.)

Gavez (Symphytum officinale L.)

BILJNI PREPARATI GAVEZA (ISKLJUČIVO ZA SPOLJNJU UPOTREBU):  Symphytum officinale L.                                               

– TINKTURA, GAVEZ HSS, hidroetanolni ekstrakt sušenih delova biljke, DER 1:5 (Ph.Eur.) i

– MATIČNA TINKTURA, GAVEZ TM, hidroetanolni ekstrakt svežih delova biljke, DER 1:2 (Ph. Fra.).

– Tinctura symphyti 1:5 DER 1:5 AD USUM EXTERNUM)

– Symphyti folii/ radicis recentis extractum ethanolicum liquidum DER 1:2 AD USUM EXTERNUM)

Preparati gaveza su namenjeni kod problema lokomotornog sistema i kože, hematoma – modrica, istegnutih mišića i tetiva, uganuća i povreda kostiju, sportskih povreda.

Biljka koja više od svih biljaka na svetu sadrži alantoin (allantoine).

– ubrzava zarastanje kostiju i tkiva (regenerator i kozmetik)
– kod neuralgičnih bolova, posebno jakih bolova lica
– snažno deluje na centralni nervni sistem, kod tretmana neuralgija (upale živaca)
– kod gihta (lagano umasirati)
– protiv tromboflebita (upale vena)
– kod iščašenja zglobova i osteoartitisa kolena
– kod povrede živaca i kičmenog stuba
– reume i artitisa

BILJNI PREPARATI GAVEZA (ISKLJUČIVO ZA SPOLJNJU UPOTREBU):  Symphytum officinale L.                                               

– TINKTURA, GAVEZ HSS, hidroetanolni ekstrakt sušenih delova biljke, DER 1:5 (Ph.Eur.) i

– MATIČNA TINKTURA, GAVEZ TM, hidroetanolni ekstrakt svežih delova biljke, DER 1:2 (Ph. Fra.).

– Tinctura symphyti 1:5 DER 1:5 AD USUM EXTERNUM)

– Symphyti folii/ radicis recentis extractum ethanolicum liquidum DER 1:2 AD USUM EXTERNUM)

Preparati gaveza su namenjeni kod problema lokomotornog sistema i kože, hematoma – modrica, istegnutih mišića i tetiva, uganuća i povreda kostiju, sportskih povreda.

ATC:

– antiinflamatik, – pomaže stvaranje kalusa, – antimitotik.

 

U skladu sa:

1) Based on Article 10a of Directive 2001/83/EC as amended (well-established use), Based on Article 16d(1), Article 16f and Article 16h of Directive 2001/83/EC as amended (traditional use), DIRECTIVE 2004/24/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 31 March 2004.

2) Eu. Ph. 8  monografijom: Symphytum officinale ad praeparationes homoeopathicas, method 3a,

3) European Medicines Agency, London, 5 May 2015, Doc. Ref.: EMA/HMPC/572846/2009, Committee on Herbal Medicinal Products (HMPC): European Union herbal monograph on Symphytum officinale L., radix

4) European Medicines Agency, London, 5 May 2015, Doc. Ref.: EMA/HMPC/572844/2009,Committee on Herbal Medicinal Products (HMPC): Assessment report on Symphytum officinale L., radix

Based on Article 16d(1), Article 16f and Article 16h of Directive 2001/83/EC as amended (traditional use)

5) Deutsches Homöopathisches Arzneibuch – HAB: method 3a;

6) Pharmacopée française 2007: Symphytum officinale ad praeparationes homoeopathicass

(CONSOUDE pour préparations homéopathiques), method 3a;

 

a) Symphytum officinale, folium (Comfrey fresh, leaf before flowering),

b) Symphytum officinale, radix (Comfrey fresh, root after flowering).

 

Biljni preparati u tečnom obliku (nerazblaženi ili razblaženi) za lokalnu upotrebu.

 

Sastav:

a) tečni ekstrakt (DER 1:2), ekstrakcioni rastvarač etanol 65% (v/v),

 

Symphytum officinale L.  sadrži 97 istraženih hemijskih jedinjenja koja ispoljavaju 448 dejstava (*podaci ažurirani juna 2017).

 

Sadržaj:

a) minimalno 0,025% m/m alantoina (allantoine) (MF: C4H6N4O3, MW: 158,11544 g/mol−1),

b) u većoj koncentraciji sadrži silicijumovu i rozmarinsku kiselinu, beta-karoten, mukopolisaharide,

c) više od svih biljaka sadrži alantoin (allantoine) – koren 25,5 ppt, list 20 ppt, pirokatehine (katehol), asparagin (asparagine-najvise posle Glycyrrhiza glabra),

d) list sadrži do 89 % a koren do 86,2 % vode.

 

Indikacije: biljni preparati su namenjeni poboljšanju opšteg stanja organizma kroz razna naučno dokazana dejstva.

Upotreba kod kožnih tegoba, uganuća i preloma kostiju.

Efikasno pomaže kod sportskih povreda.

 

Dr. Džems Djuk (Dr. James Duke) u Handbook of Medicinal Herbs, 2nd Ed. (2002). CRC Press, navodi sledeće:

– ima jako dejstvo kod: modrica-hematoma, duodenalnog ulcera, inflamacija, ulkusa rožnjače (H16.0), uganuća.

– delotvoran kod: artroze, krvarenja, bronhitisa, ujeda insekata,  Ca. (kostiju i pluća),  dekubitisa, dermatoza, kolitisa, ekcema, enteritisa, epikondilitisa, fraktura, istegnuća mišića i tetiva, gastritisa, gingivitisa, visokog krvnog pritiska, mastitisa, psorijaze, reumatizma, bolova, faringitisa, osipa (raš), tendovaginitisa, tonzilitisa, TB,  Tu,  Ulcus cruris-a, rana, iritacije kože usled trenja, sportskih povreda.  

– u narodnoj medicini kod: adenopatije, amenoreje, anemije, angine, astme, bolova u leđima, kandidijaze, katara,  holecistitisa, kongestije, konstipacije, kontuzija, dijabetesa, dijareje, dizenterije, dismenoreje, dispepsije, peska, gastričnog ulkusa, gonoreje, gihta, hematemeze, hemoptizije, hemoroida, hepatitisa, hernije, histerije, leukoreje, metroragije, miozitisa, nefritisa, oftalmije, ostitisa, pleuritisa, respiratornih tegoba, skrofula, upale grla, ulcera, vaginitisa, varikoza, veneričnih bolesti (VD), gljivičnih infekcija, stomatitisa,  opekotina od sunca, otoka-edema, kašlja, gorušice, pertusisa, promuklosti, svraba, krvarenja iz donjeg dela GIT-a,

– spoljašnja primena kod: akni, žuljeva, rana, zatvorenih preloma, nagnječenja, … 

– upotrebljava se kao: jak antiinflamatik, zatim kao analgetik, antileukocit, antimikotik, antimutagenik, antipsorijatik, antiTu, adstrigent, promoter kalusa, karcinogenik (jetra), demulcent, emolijent, hepatotoksik, hipotenziv, uterotonik, vulnerar, a u tradicionalnoj medicini kao alternativ, antiaging, antihemoragik, ekspektorant, hemostatik, tonik.

Monografija nemačke E komisije (Commission E Monographs), terapijski vodič za biljne lekove, preporučuje Symphytum officinale isključivo za spoljnu upotrebu, za tretman povreda kostiju i kože.

Doziranje i način primene: do 2 mL (80 kapi).

Biljni preparat GAVEZ HSS i TM:

preporučena dnevna doza (PDD): do 2 mL.

Lokalna primena.  

NE PREPORUČUJE SE ORALNA UPOTREBA ZBOG HEPATOTOKSIČNOSTI I KANCEROGENOSTI!

PREPARATE GAVEZA BILJNE ALHEMIJE NE KORISTITI DUŽE OD 6 NEDELJA GODIŠNJE ILI 100 mL ZBOG MOGUĆE INTOKSIKACIJE I KOD PERKUTANE UPOTREBE! 

Dnevni unos pirolizidinskih alkaloida (pyrrolizidine alkaloids) mora biti ispod 0.35 µg (EMEA), odnosno 100 µg (Commission E – svež koren sadrži 2,4% m/m).

Za više detalja videti “Public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs)” (EMA/HMPC/893108/2011).

Upotreba na koži: aplicirati na obolelo mesto u tankom sloju ili obliku impregniranog zavoja. 

Napraviti pauzu posle 4 nedelje neprekidne upotrebe.

Ne primenjivati na oštećenoj ili iritiranoj koži, izbegavati kontakt sa očima i sluzokožom.

Kontraindikacije: preosetljivost na aktivne supstance, preosetljivost na biljke porodice (genus Symphytum, family Boraginaceae). 

Interakcije: nisu poznate.

Čuvanje: na tamnom, suvom i hladnom mestu do 20˚C, van domašaja dece i izlaganja EM zračenju, u dobro zatvorenoj originalnoj ambalaži. 

Rok upotrebe: 5 godina, posle prvog otvaranja 6 meseci. Zbog sadržaja alkohola (65%), a ako se čuva po preporučenim uslovima, rok trajanja je neograničen. 

Pakovanje: 50 mL i 100 mL, standardne farmaceutske braon bočice, 250 mL, 500 mL, 1L i 5 L na zahtev.

 

Nutritivne informacije (nije primenljivo- nije za oralnu upotrebu):

GAVEZ HSS i TM:

energetska vrednost u 100 mL: 1504 kJ/ 360 kcal,

u preporučenoj dnevnoj dozi (PDD) 2 mL: 30kJ/ 7,17 kcal,

suve materije (DR) više od 1,5% (Fr. Ph.).

 

Bez konzervanasa, proteina, masti i ugljenih hidrata. GAVEZ HSS i TM su rukom rađeni proizvodi. 

CENOVNIK

LIST

TINKTURA, GAVEZ HSS LIST, DER 1:5 – hidroetanolni ekstrakt sušenog lista (Ph. Eur.),

LIST  HSS, 50 mL/ 500,00 RSD; 100 mL/ 1000,00 RSD;

MATIČNA TINKTURA, GAVEZ TM LIST, DER 1:2– hidroetanolni tečni ekstrakt svežeg lista, (Ph. Fra.), 

LIST TM, 50 mL/ 600,00 RSD; 100 mL/ 1200,00 RSD;

KOREN

TINKTURA – GAVEZ HSS KOREN, DER 1:5, hidroetanolni ekstrakt sušenog korena (Ph. Eur.),

KOREN  HSS, 50 mL/ 600,00 RSD; 100 mL/ 1200,00 RSD;

MATIČNA TINKTURA, GAVEZ TM KOREN, DER 1:2, hidroetanolni tečni ekstrakt svežeg korena, (Ph. Fra.),  

KOREN  TM, 50 mL/ 720,00 RSD; 100 mL/ 1440,00 RSD.

 

Podaci ažurirani januara 2020. 

Poželjno je pogledati sve informacije na:

http://www.biljni-preparati.com/preparati/gavez-symphytum-officinale-l/                                

redosled dejstava po broju bioaktivnih jedinjenja

Antioxidant, Cancer-Preventive, Antidiabetic, Pesticide, Immunostimulant, Cardioprotective, Hypotensive, Diuretic, Antiradicular, Antihepatotoxic, Hypocholesterolemic, Anxiolytic, Antiinflammatory, Antiatherosclerotic, Antiarthritic, Antidepressant, Antiulcer, Antiosteoporotic, Antihypertensive, Antitumor, Antialzheimeran, Antimutagenic, Vulnerary, Immunomodulator, Antibacterial, AntiHIV, Anticataract, Analgesic, Antisyndrome-X, Antiviral, Vasodilator, Hypoglycemic, Antiobesity, Antialcoholic, Hepatoprotective, Antiaggregant, Antiacne, Antifatigue, AntiLyme, Antihangover, Antispasmodic, Antirheumatic, Hypoglycemic, Antiobesity, Hepatoprotective, Antialcoholic, Antiinsomniac, Antimenopausal, Anticoronary, Antihistaminic, Aldose-Reductase-Inhibitor, Antileukotriene, AntiPMS, Allergenic, Antimaculitic, Antiedemic, Antiasthmatic, Antiproliferant, Anticlimacteric, Antiallergic, Antiproliferant, Anticlimacteric, Antiallergic, Laxative, Antiaging, Calcium-Antagonist, Sedative, Ornithine-Decarboxylase-Inhibitor, Antiseptic, Antimigraine, Antihyperthyroid, Antiophidic, Anticonvulsant, Antigonadotropic, Insulinogenic, Antitumor (Lung), Antidecubitic, AntiRaynaud’s, Carcinogenic,Tranquilizer, …

 

Reference

Stitt, P. A. Why George Should Eat Broccoli. Dougherty Co, Milwaukee, WI, 1990, 399 pp.

Challem, J., Berkson, Burt, and Smith, Melissa Dianne. 2000. Syndrome X – The complete nutritional program to prevent and reservse insulin resistance. John Wiley & Sons, New York. 272 pp. $24.95

Ohnishi, M., Morishita, H., Iwahashi, H., Toda, S., Shirataki, Y., Kimura, M., and Kido, R. 1993. Inhibitory Effects of Chlorogenic Acids on Linoleic Acid Peroxidation and Haemolysis. Phytochemistry. 36(3): 579-583. 1994.

Werbach, M. 1993. Healing with Food. Harper Collins, New York, 443 pp.

Pizzorno, J.E. and Murray, M.T. 1985. A Textbook of Natural Medicine. John Bastyr College Publications, Seattle, Washington

Economic & Medicinal Plant Research, 5: 363.

Economic & Medicinal Plant Research, 6: 189.

Economic & Medicinal Plant Research, 6: 235.

Martindale’s 29th

Forest H. Nielsen, USDA, Grand Forks, various publications.

Huang, K. C. 1993. The Pharmacology of Chinese Herbs. CRC Press, Boca Raton, FL 388 pp.

Jeffery B. Harborne and H. Baxter, eds. 1983. Phytochemical Dictionary. A Handbook of Bioactive Compounds from Plants. Taylor & Frost, London. 791 pp.

Advance in Chinese Medicinal Materials Research. 1985. Eds. H. M. Chang, H. W. Yeung, W. -W. Tso and A. Koo. World Scientific Publishing Co., Philadelphia Pa., page 210.

Davies, S., and Stewart, A. 1990. Nutritional Medicine. Avon Books, New York. 509pp.

Int. J. Immunopharmacology. Vol 10: 729, 1988.

Hagerman, A.E. Tannin-Protein Interactions. Phenolic Compounds in Food and Their Effects on Health, Ch.19.

Borchard, R. E., Barnes, C. D., and Eltherton, L. G. 1991. Drug Dosage in Laboratory Animals: A Handbook. (3rd Ed.) The Telford Press, Inc., P. O. Box 287, Caldwell NJ 07006.

Izvor: dr Duke, James A.

Podaci ažurirani oktobra 2016.

Upotreba gaveza (Symphytum officinale L.) sa referencama.

Symphytum officinale (Boraginaceae)  Common names Comfrey; Borraja; Consoude; Buyuk Karakafesotu; Hirehari-So; Consuelda; Liane Chique; Bourrache
analgetik Brutus, T.C., and A.V. Pierce-Noel. 1960. Les Plantes et les Legumes d’Hati qui Guerissent. Imprimerie De L’Etat, Port-Au-Prince, Haiti.
antidijareik ANON. 1978. List of Plants. Kyoto Herbal Garden, Parmacognostic Research Lab., Central Research Division, Takeda Chem. Industries, Ltd., Ichijoji, Sakyoku, Kyoto, Japan.
adstrigent Uphof, J.C. Th. 1968. Dictionary of economic plants. 2nd ed. Verlag von J. Cramer.
adstrigent Steinmetz, E.F. 1957. codex Vegetabilis. Published by the author, Amsterdam.
Ca Hartwell, J.L. 1967-71. Plants used against cancer. A survey. Lloydia 30-34.
cikatrizant Steinmetz, E.F. 1957. codex Vegetabilis. Published by the author, Amsterdam.
cirkulatonik Lost Crops of the Incas.
demulcent Steinmetz, E.F. 1957. codex Vegetabilis. Published by the author, Amsterdam.
demulcent Uphof, J.C. Th. 1968. Dictionary of economic plants. 2nd ed. Verlag von J. Cramer.
dijareja Brutus, T.C., and A.V. Pierce-Noel. 1960. Les Plantes et les Legumes d’Hati qui Guerissent. Imprimerie De L’Etat, Port-Au-Prince, Haiti.
diuretik Liogier, Alain Henri. 1974. Diccionario Botanico de Nombres Vulgares de la Espanola. Universidad Nacional Pedro Henriquez Urena, Santo Domingo.
ekspektorans Steinmetz, E.F. 1957. codex Vegetabilis. Published by the author, Amsterdam.
hemoptizija Uphof, J.C. Th. 1968. Dictionary of economic plants. 2nd ed. Verlag von J. Cramer.
hemostatik Steinmetz, E.F. 1957. codex Vegetabilis. Published by the author, Amsterdam.
antiinflamatik Uphof, J.C. Th. 1968. Dictionary of economic plants. 2nd ed. Verlag von J. Cramer.
antiinflamatik Lost Crops of the Incas.
pluća Uphof, J.C. Th. 1968. Dictionary of economic plants. 2nd ed. Verlag von J. Cramer.
grudni Liogier, Alain Henri. 1974. Diccionario Botanico de Nombres Vulgares de la Espanola. Universidad Nacional Pedro Henriquez Urena, Santo Domingo.
sedativ Steinmetz, E.F. 1957. codex Vegetabilis. Published by the author, Amsterdam.
povrede Font Query, P. 1979. Plantas Medicinales el Dioscorides Renovado. Editorial Labor, S.A. Barcelona. 5th Ed.
stimulant Steinmetz, E.F. 1957. codex Vegetabilis. Published by the author, Amsterdam.
sudorifik Liogier, Alain Henri. 1974. Diccionario Botanico de Nombres Vulgares de la Espanola. Universidad Nacional Pedro Henriquez Urena, Santo Domingo.
antiedemik Uphof, J.C. Th. 1968. Dictionary of economic plants. 2nd ed. Verlag von J. Cramer.

Data by National Agricultural Library

Comfrey   

for Professional

Scientific Name(s): Symphytum officinale L., S. asperum Lepechin, S. tuberosumL., Symphytum x uplandicum Nyman. Family: Boraginaceae (Borage)

Common Name(s): Comfrey , bruisewort , blackwort , knitbone , radix consolidate , Russian comfrey , slippery root

Uses Therapeutic use of comfrey is limited because of its toxicity. A limited number of clinical trials show short-term efficacy of topically applied, alkaloid-free comfrey preparations in skin abrasions and inflammatory conditions. Although not examined in clinical trials, comfrey may possess antifungal and anticancer activity.

Dosing Oral use of comfrey is not supported because of potential hepatotoxicity. Additionally, because externally applied alkaloids are well absorbed and detected in the urine, topical use of comfrey should not exceed an alkaloid exposure of 100 mcg/day. Limited trials have evaluated the efficacy of alkaloid-free preparations for topical use; however, these studies do not report on hepatic laboratory indices of study participants.

Contraindications Comfrey is not recommended for internal use because of the hepatotoxic pyrrolizidine alkaloid content. Patients with hypersensitivity or allergic reactions to the plant should avoid external use. Use is contraindicated during pregnancy and lactation, in infants, and in patients with liver or kidney disease.

Pregnancy/Lactation Contraindicated because of documented adverse effects. Pyrrolizidine alkaloids have abortifacient effects and increase the risk of fatal hepatic veno-occlusive disease. Animal experiments have detected alkaloids in breast milk.

Interactions None well documented.

Adverse Reactions Neither internal nor extensive topical use of comfrey is recommended because of numerous reports of liver toxicity (see Toxicology). Case reports show hepatic veno-occlusive disease and pulmonary hypertension related to comfrey use. Infants are more susceptible to pyrrolizidine-related, veno-occlusive disease; therefore, the use of comfrey in this population is contraindicated. 

Toxicology The Food and Drug Administration (FDA) released an advisory in July 2001 recommending that comfrey products be removed from the market because of cases of hepatic veno-occlusive disease. Comfrey is generally considered unsafe, with numerous toxicological effects in animals and humans.

Botany Comfrey is a perennial plant found in moist grasslands in western Asia, as well as in North America. It grows to heights of 50 to 150 cm and has long, hairy lanceolate leaves and bell-shaped, red-violet or yellowish flowers. S. x uplandicum Nyman is a hybrid of S. officinale and S. asperum , and has been cultivated to contain insignificant amounts of alkaloids in the aerial parts of the plant. 1 , 2 , 3

History Comfrey has been cultivated in Japan as a green vegetable and has been used as an herbal medicine for more than 2,000 years. Comfrey’s original name, knitbone, derives from the external use of poultices of its leaves and roots to heal burns, sprains, swelling, and bruises. In Western Europe, comfrey has been used topically for treating inflammatory disorders such as arthritis, gout, and thrombophlebitis, and internally for treating diarrhea. Comfrey has been claimed to heal gastric ulcers and hemorrhoids, and to suppress bronchial congestion and inflammation. Comfrey distribution is restricted in Germany and Canada because of its substantial toxicity. 2 , 4 

Chemistry Numerous hepatotoxic pyrrolizidine alkaloids with differing toxicities have been identified in the plant, including symphytine, echimidine, intermedine, symviridine, and lasiocarpine (retronecine mono- and diester alkaloids). Roots contain a 100-fold higher alkaloid content than the aerial portions. 2 , 5 , 6

The healing action of poultices of comfrey roots and leaves may be related to the presence of allantoin. The underground roots contain allantoin 0.6% to 0.7% and tannin 4% to 6.5%; the leaves contain a higher proportion of tannin relative to allantoin. The roots also contain rosmarinic and lithspermic acid. 7 , 8 , 9 , 10

Large amounts of mucilage, fructanes, and starch are found in the leaves and roots, 11 , 12 while a pentacyclic triterpene glycoside of oleanolic acid was identified in the root. 9 , 10

 

Uses and Pharmacology The therapeutic use of comfrey is due in part to allantoin and rosmarinic acid content, but it is limited by the toxicity of pyrrolizidine alkaloids. 4 Controlled cultivation of S. x uplandicum is said to produce a plant devoid of the toxic alkaloids in the aerial plats, enabling the production of relatively nontoxic comfrey preparations. 3 Pyrrolizidine alkaloid-free preparations of comfrey have been used in clinical studies in Germany. 

Inflammation A limited number of clinical trials have been conducted to assess the efficacy of topically applied, alkaloid-free comfrey preparations in ankle sprains, osteoarthritic knee conditions, and back pain/myalgia. 13 , 14 Outcome measures include patient assessment of pain and mobility, as well as measures of ankle swelling and clinician evaluations. Most studies show a statistically significant advantage of active preparation over placebo in the short term; however, because many of these trials have been conducted by product manufacturers, the possibility of publishing bias exists. 3 , 11 , 12 , 14 , 15 , 16 Other open-label or single-blind trials with topical comfrey preparations have been conducted; however study design limits the validity of the results. 17 , 18 , 19 Preparations generally contained a 35% liquid root extract from which toxic alkaloids were removed and standardized to allantoin 0.2% to 0.5%, 11 , 12 , 15 , 19 or to a preparation with 10% extract of S. x uplandicum aerial parts. 3 , 16 Duration of use ranged from 5 days to 3 weeks in these studies. The studies report no adverse effects, although liver function test results were not reported.

Mechanisms of action include effects on platelet activating factor, as well as on the synthesis of the enzymes catalase and superoxide dimutase. 20 , 21

Wound healing The use of a dermal preparation of comfrey derived from alkaloid-free cultivars of S. x uplandicum has been studied in limited clinical trials. Applied to fresh abrasions, a 10% preparation showed faster decreases in wound size and shorter times to healing, with no cutaneous reactions to the preparation reported. 3 , 22 The preparations were applied to the skin over short time periods (days) only. Efficacy in wound healing may be related to the presence of allantoin, rosmarinic acid, or another hydrocolloid polysaccharide. 23 , 24 

Other effects
Antifungal activity
Aqueous extracts from comfrey leaves strongly inhibited plant pathogenic fungi, most likely because of the plant’s phenolic compounds. 25

Cancer Various extracts and fractions of S. officinale have inhibited tumor cell proliferation and exerted antimitotic effects in animal and in vitro experiments. 26 , 27 , 28 , 29

Hormonal Lithospermic acid isolated from the root appears to have antigonadotropic activity. 9 

Dosage The oral use of comfrey cannot be supported because of potential hepatotoxicity. Because externally applied alkaloids are well absorbed (detected in the urine), topical use of comfrey should not exceed an alkaloid exposure of 100 mcg/day. 2

Limited trials have evaluated the efficacy of alkaloid-free preparations for topical use; however, these studies do not report on hepatic laboratory indices of the participants.

Pregnancy/Lactation Avoid use because of documented adverse effects. Pyrrolizidine alkaloids have abortifacient effects and increase the risk of fatal hepatic veno-occlusive disease. 30 , 31 , 32 An extract of S. officinale has been reported to enhance uterine tone. 33Animal experiments have detected comfrey alkaloids in breast milk. 34 , 35 

Interactions Case reports are lacking. Experimental evidence exists of the potentiation of toxicity of comfrey’s alkaloids by phenobarbital via the cytochrome P450 pathway. 2 

Adverse Reactions Neither internal nor extensive topical use of comfrey can be recommended because of numerous reports of liver toxicity (see Toxicology). Case reports show hepatic veno-occlusive disease and pulmonary hypertension related to comfrey use. 236 Infants are more susceptible to pyrrolizidine-related, veno-occlusive disease; therefore, the use of comfrey in this population is contraindicated. 2 

Toxicology

Hepatotoxic effects The FDA released an advisory in July 2001 recommending that comfrey products be removed from the market following several cases of hepatic veno-occlusive disease in which the destruction or obliteration of small hepatic veins led to cirrhosis and, eventually, liver failure. Also in 2001, the Federal Trade Commission brought enforcement action against a company marketing comfrey-containing products. The parties agreed to a preliminary injunction that prohibited the company from marketing any comfrey-containing products intended for internal use or use on open wounds, as well as requiring a warning on comfrey products intended for external use. 37 , 38 , 39 , 40 , 41 , 42 , 43

Human poisonings with pyrrolizidine alkaloids are usually accidental and may be caused by ingestion of contaminated flour, milk, certain goat products that are resistant to the alkaloids, honey produced by bees fed on pyrrolizidine-containing weeds, and consumption of certain herbal or bush teas. It also may be caused by comfrey used in salads. 4 , 5 , 34 , 35 

Carcinogenicity S. officinale extract and components lasiocarpine and symphytine are carcinogenic in rats, possibly via genotoxic mechanisms 44 , 45 , 46 , 47 ; however, an association of comfrey consumption with cancer in humans is lacking. 2

A pyrrolizidine alkaloid-free liquid extract of comfrey root was not mutagenic when tested by the bacterial reverse mutation assay. 48 

Bibliography

  1. Symphytum officinale L. USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , December 2009). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
    2. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr . 2000;3(4a):501-508.
    3. Kucera M, Barna M, Horàcek O, Kàlal J, Kucera A, Hladìkova M. Topical symphytum herb concentrate cream against myalgia: a randomized controlled double-blind clinical study. Adv Ther . 2005;22(6):681-692.
    4. Stewart MJ, Steenkamp V. Pyrrolizidine poisoning: a neglected area in human toxicology. Ther Drug Monit . 2001;23(6):698-708.
    5. Rode D. Comfrey toxicity revisited. Trends Pharmacol Sci . 2002;23(11):497-499.
    6. Furuya T, Hikichi M. Alkaloids and triterpenoids of Symphytum officinale . Phytochemistry . 1971;10(9):2217-2220.
    7. Tyler VE. The Honest Herbal . 3rd ed. New York, NY: Pharmaceutical Press; 1972.
    8. Mutterlein R, Arnorld CG. Investigations concerning the content and the pattern of pyrrolizidine alkaloids in Symphytum officinale L. (comfrey). Pharm Ztg Wiss . 1993;138(5/6):119-125.
    9. Wagner H, Hörhammer L, Frank U. Lithospermic acid, the antihormonally active principle of Lycopus europaeus L. and Symphytum officinale 3. Ingredients of medicinal plants with hormonal and antihormonal-like effect [in German]. Arzneimittelforschung . 1970;20(5):705-713.
    10. Ahmad VU, Noorwala M, Mohammad FV, Sener B. A new triterpene glycoside from the roots of Symphytum officinale . J Nat Prod . 1993;56(3):329-334.
    11. Koll R, Buhr M, Dieter R, et al. Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distorsions: results of a multicenter, randomized, placebo-controlled, double-blind study. Phytomedicine . 2004;11(6):470-477.
    12. Giannetti BM, Staiger C, Bulitta M, Predel HG. Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial. Br J Sports Med . 2010;44(9):637-641.
    13. Bleakley CM, McDonough SM, MacAuley DC. Some conservative strategies are effective when added to controlled mobilisation with external support after acute ankle sprain: a systematic review. Aust J Physiother . 2008;54(1):7-20.
    14. Petersen G, Lorkowski G, Kasper FR, Gottwold R, Lucker PW. Anti-inflammatory activity of a pyrrolizidine alkaloid-free extract of roots of Symphytum officinale in humans. Planta Med . 1993;59(51):A703-A704.
    15. Grube B, Grünwald J, Krug L, Staiger C. Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial. Phytomedicine . 2007;14(1):2-10.
    16. Kucera M, Barna M, Horácek O, Kováriková J, Kucera A. Efficacy and safety of topically applied Symphytum herb extract cream in the treatment of ankle distortion: results of a randomized controlled clinical double blind study. Wien Med Wochenschr . 2004;154(21-22):498-507.
    17. Koll R, Klingenburg S. Therapeutic characteristance and tolerance of topical comfrey preparations. Results of an observational study of patients [in German]. Fortschr Med Orig . 2002;120(1):1-9.
    18. Kucera M, Kálal J, Polesná Z. Effects of Symphytum ointment on muscular symptoms and functional locomotor disturbances. Adv Ther . 2000;17(4):204-210.
    19. Predel HG, Giannetti B, Koll R, Bulitta M, Staiger C. Efficacy of a comfrey root extract ointment in comparison to a diclofenac gel in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study. Phytomedicine . 2005;12(10):707-714.
    20. Tunón H, Olavsdotter C, Bohlin L. Evaluation of anti-inflammatory activity of some Swedish medicinal plants. Inhibition of prostaglandin biosynthesis and PAF-induced exocytosis. J Ethnopharmacol . 1995;48(2):61-76.
    21. Dolganiuc A, Radu LD, Olinescu A. The effect of products of plant and microbial origin on phagocytic function and on the release of oxygen free radicals by mouse peritoneal macrophages [in Romanian]. Bacteriol Virusol Parazitol Epidemiol . 1997;42(1-2):65-69.
    22. Barna M, Kucera A, Hladícova M, Kucera M. Wound healing effects of a Symphytum herb extract cream ( Symphytum x uplandicum NYMAN: ): results of a randomized, controlled double-blind study [in German]. Wien Med Wochenschr . 2007;157(21-22):569-574.
    23. Andres R, Brenneisen R, Clerc JT. Relating antiphlogistic efficacy of dermatics containing extracts of Symphytum officinale to chemical profiles. Planta Med . 1989;55(7):643-644.
    24. Franz G. Polysaccharides in pharmacy: current applications and future concepts. Planta Med . 1989;55(6):493-497.
    25. Karavaev VA, Solntsev MK, Iurina TP, Iurina EV, Poliakova IB, Kuznetsov AM. Antifungal activity of aqueous extracts of the leaves of cowparsnip and comfrey [in Russian]. Izv Akad Nauk Ser Biol . 2001;4:435-441.
    26. Yeong ML, Clark SP, Waring JM, Wilson RD, Wakefield SJ. The effects of comfrey derived pyrrolizidine alkaloids on rat liver. Pathology . 1991;23(1):35-38.
    27. Awang DV. Comfrey. Can Pharm J . 1987;120:101-104.
    28. Gomes MF, de Oliveira Massoco C, Xavier JG, Bonamin LV. Comfrey ( Symphytum Officinale . L.) and experimental hepatic carcinogenesis: a short-term carcinogenesis model study. Evid Based Complement Alternat Med . 2010;7(2):197-202.
    29. Olinescu A, Manda G, Neagu M, Hristescu S, Dasanu C. Action of some proteic and carbohydrate components of Symphytum officinale upon normal and neoplastic cells. Roum Arch Microbiol Immunol . 1993;52(2):73-80.
    30. Brinker FJ. Herb Contraindications and Drug Interactions . 2nd ed. Sandy, OR: Eclectic Medical Publications;1998.
    31. Newall CA, Anderson LA, Phillipson JD, eds. Herbal Medicines: A Guide for Health-Care Professionals . London: Pharmaceutical Press; 1996.
    32. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109(3):227-235.
    33. Shipochliev T. Uterotonic action of extracts from a group of medicinal plants [in Bulgarian]. Vet Med Nauki . 1981;18(4):94-98.
    34. Schoental R. Health hazards of pyrrolizidine alkaloids: a short review. Toxicol Lett . 1982;10(4):323-326.
    35. Panter KE, James LF. Natural plant toxicants in milk: a review. J Anim Sci . 1990;68(3):892-904.
    36. Györik S, Stricker H. Severe pulmonary hypertension possibly due to pyrrolizidine alkaloids in polyphytotherapy. Swiss Med Wkly . 2009;139(13-14):210-211.
    37. U.S. Food and Drug Administration. Center for Food Safety and Applied Nutrition. FDA advises dietary supplement manufacturers to remove comfrey products from the market. July 6, 2001. http://www.cfsan.fda.gov/~dms/dspltr06.html . Accessed January 10, 2006
    38. Mattocks AR. Toxic pyrrolizidine alkaloids in comfrey. Lancet . 1980;2(8204):1136-1137.
    39. Ridker PM, Ohkuma S, McDermott WV, Trey C, Huxtable RJ. Hepatic venocclusive disease associated with the consumption of pyrrolizidine-containing dietary supplements. Gastroenterology . 1985;88(4):1050-1054.
    40. Larrey D. Liver involvement in the course of phytotherapy [in French]. Presse Med . 1994;23(15):691-693.
    41. Kumana CR, Ng M, Lin HJ, Ko W, Wu PC, Todd D. Hepatic veno-occlusive disease due to toxic alkaloid herbal tea. Lancet . 1983;2(8363):1360-1361.
    42. Yeong ML, Swinburn B, Kennedy M, Nicholson G. Hepatic veno-occlusive disease associated with comfrey ingestion. J Gastroenterol Hepatol . 1990;5(2):211-214.
    43. Mattocks AR. Toxicity of pyrrolizidine alkaloids. Nature . 1968;217(5130):723-728.
    44. Svoboda DJ, Reddy JK. Malignant tumors in rats given lasiocarpine. Cancer Res . 1972;32(5):908-913.
    45. Hirono I, Haga M, Fujii M, et al. Induction of hepatic tumors in rats by senkirkine and symphytine. J Natl Cancer Inst . 1979;63(2):469-472.
    46. Hirono I, Mori H, Haga M. Carcinogenic activity of Symphytum officinale . J Natl Cancer Inst . 1978;61(3):865-869.
    47. Mei N, Guo L, Fu PP, Heflich RH, Chen T. Mutagenicity of comfrey ( Symphytum Officinale ) in rat liver. Br J Cancer . 2005;92(5):873-875.
    48. Benedek B, Ziegler A, Ottersbach P. Absence of mutagenic effects of a particular Symphytum officinale L. liquid extract in the bacterial reverse mutation assay. Phytother Res . 2010;24(3):466-468.

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DOZIRANJE, INTOKSIKACIJA

External  dosage  of  pyrrolizidine  alkaloids  (PAs)  maximum  100  g/day  for  a  maximum  4–6 weeks/year.

Comfrey root may cause liver damage if taken internally.

Contains PAs. Internal use may cause severe hepatic damage.

PAs are toxic to humans, with liver damage with cirrhosis and ascites, or seneciosis, or veno-occlusive disease (VOD) reported in almost all  cases  of  severe  or  fatal  intoxications,  from  intakes  of  0.5  mg/kg  to  3.3  mg/kg.

x x x x x

PREPORUKE RAZNIH AUTORA

Dosages:

Do  not  use; 

do  not  use  root; 

2-4  g  root  as  tea  3×day;

2 tsp (= ~7.4 g) root in hot tea;

2-4 ml liquid root extract;

2-4 ml liquid extract (1:1 in 25% EthOH) 3×day;

2-8 ml liquid leaf extract (1:1 in 25% EtOH) 3×day;

2-8 g leaf in tea 3×day;

0.25-0.5 cup fresh leaf;

6-12 g dry leaf;

9 g dry leaf 45 ml EtOH/ 45 ml water;

1-3 cups tea/day (5-10 g herb) remembering PAs.

Comfrey (Symphytum officinale)

Synonyms / Common Names / Related Terms

7-Acetylintermedine, acetyllcopsamine, allantoin, allantoin-beta-cyclodextrin, anadoline, asperum polymer, ass ear, assear, asses-ears, Beinwell (German), black root, black wort, blackwort, blue comfrey, bocking 14, boneset, Boraginaceae (family), Borago-Symphytum, borraja, bourrache, bruisewort, bulbous comfrey, buyuk karakafesotu, Caucasian comfrey, comfrey extract, comfrey herb, comfrey root, common comfrey, comphrey, consolida, consolida aspra (Italian), consolidae radix, consolida majoris, consolide maggiore (Italian), consormol, consoude, consoude grande (French), consoude rude (French), consound, consuelda (Spanish), creeping comfrey, Crimean comfrey, echimidine, Extr. Rad. Symphyti, glucofructan, great comfrey, ground comfrey root, gum plant, healing blade, healing herb, heliotrine, hirehari-so, hydroxycinnamate-derived polymer, integerrimine, intermedine, knitback, knitbone, Kytta-Balsam® f, Kytta-Plasma® f, Kytta-Salbe® f, lasiocarpine, liane chique, lithospermic acid, lycopsamine, medicinal comfrey, mucopolysaccharides, navadni gabez (Slovenian), nipbone, okopnik sherohovaty (Russian), oreille d’ane (French), otonecine- pyrrolizidine alkaloids, prickley comfrey, pyrrolizidine alkaloid, Quaker comfrey, radix symphyti, rauher Beinwell (German), rauhe Wallwurz (German), Reinweld (German), retronecine, retrorsine, retrorsine N-oxide, riddelliine, ridelliine N-oxide, rosmarinic acid, rough comfrey, ru kulsukker (Danish), Russian comfrey, ruwe smeerworted (Dutch), salsify, saponins, senecionine, senecionine N-oxide, seneciphylline, senkirkine, simfit (Italian), slippery root, S. x uplandicum, symlandine, symphyti herba, symphyti folium, symphyti radix, symphytine, symphytum alkaloids, Symphytum asperrimum Donn, Symphytum asperumSymphytum asperum Lepechin, Symphytum asperum xofficinale, Symphytum bulbosum, Symphytum caucasicumSymphytum caucasicvum, Symphytum cream, Symphytum grandiflorumSymphytum ibericumSymphytum officinale Linn, Symphytum orientale, Symphytum peregrinum Lebed, Symphytum radix, Symphytum spp., Symphytum tauricum, Symphytum tuberosum, Symphytum x, Symphytum x uplandicumSymphytum x uplandicum Nyman, Syrupus de Symphyto (Spanish), tannins, tarharaunioyrtti (Finnish), the great comfrey, tuberous comfrey, 7- uplandine, wallwort, wallwurz (German), white comfrey, yalluc (Saxon), zinzinnici (Italian).

Combination products (examples): Asthma tincture (blood root, St. John’s wort, mullein, saw palmetto, wild cherry bark, goldenseal root, cayenne, comfrey, Lobelia, R/O water, 12% alcohol).

 

Mechanism of Action

Pharmacology:

  • Constituents: The roots of Symphytum officinale contain pyrrolizidine alkaloids, including symlandine, symphytine, and echimidine.8,9 Other constituents include riddelliine, riddelliine N-oxide, senecionine, senecionine N-oxide, seneciphylline, retrorsine, integerrimine, lasiocarpine and heliotrine.6 Anadoline has also been identified in a related species, Symphytum orientale.10 Eight pyrrolizidine alkaloids, including symlandine, symphytine, lycopsamine, intermedine, 7-acetyllcopsamine, 7-acetylintermedine, uplandine, and echimidine, have been identified in leaves ofSymphytum x uplandicum.11,9
  • The concentration of symphytine and echimidine varies between teas prepared from leaves purchased from different vendors.5 Nine of 11 comfrey products available in health food stores were found to contain measurable quantities of one or more alkaloids, in ranges from 0.1 to 400.0ppm.7 The highest levels were found in bulk comfrey root, followed by bulk comfrey leaf, followed by comfrey combination products.
  • Poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] was isolated from the roots of Symphytum asperum and Symphytum caucasicum.12 3-O-[beta-D-glucopyranosyl-(1–>4)-beta-D-glucopyranosyl-(1–>4)-alpha-L-arabinopyranosyl]-oleanolic acid was isolated from the ethanol-soluble portion of Symphytum officinale roots. 13
  • Mucopolysaccharides, saponins, allantoin, rosmarinic acid, tannins, and lithospermic acid are also found in comfrey.14,15,16,17,18,19,20,21
  • Antifungal effects: Extracts from the leaves of comfrey inhibited the germination of Erysiphe graminis conidia and uredospores of Puccinia graminis, resulting in diminished powdery mildew infection of plants.1 It is not clear whether comfrey has clinical antifungal effects.
  • Anti-inflammatory effectsIn vitroSymphytum x uplandicum inhibited platelet activating factor-induced exocytosis.3 In vitro, a water-soluble hydroxycinnamate-derived polymer (>1000kDa) from Symphytum asperum Lepech. inhibited degranulation of azurophil granules and superoxide generation in primed leukocytes, indicating anti-inflammatory effects.2 In animals, a water extract of comfrey altered the production of prostaglandins.22
  • Antioxidant effectsIn vitro, a water-soluble hydroxycinnamate-derived polymer (>1000kDa) from Symphytum asperum Lepech reduced the diphenylpicrylhydrazyl radical and inhibited the nonenzymatic lipid peroxidation of bovine brain extracts.2 Superoxide anion generation was also reduced.
  • In vitro, topical formulations including Symphytum officinale showed some antioxidant and free radical scavenging activities.4
  • Immune effects: In an animal study, an aqueous extract obtained from roots of Symphytum officinale initially activated the respiratory burst of macrophages and later activated the synthesis of catalase and superoxide dismutase.23 The clinical significance of this is unknown.
  • Vasoprotective effectsIn vitro, a water-soluble hydroxycinnamate-derived polymer (>1000kDa) from Symphytum asperum Lepech. inhibited degranulation of azurophil granules and superoxide generation in primed leukocytes, indicating vasoprotective effects.2

 

Pharmacodynamics/Kinetics:

  • In an animal study, topical application of a crude alcoholic extract resulted in very low absorption of pyrrolidizine alkaloids.24 0.1-0.4% of the dose was recovered in the urine over the next 24 hours.

 

References

  1. Karavaev, V. A., Solntsev, M. K., Iurina, T. P., Iurina, E. V., Poliakova, I. B., and Kuznetsov, A. M. [Antifungal activity of aqueous extracts from the leaf of cowparsnip and comfrey]. Izv Akad Nauk Ser Biol2001;(4):435-441. 11525124
  2. Barthomeuf, C. M., Debiton, E., Barbakadze, V. V., and Kemertelidze, E. P. Evaluation of the dietetic and therapeutic potential of a high molecular weight hydroxycinnamate-derived polymer from Symphytum asperum Lepech. Regarding its antioxidant, antilipoperoxidant, antiinflammatory, and cytotoxic properties.J Agric Food Chem 2001;49(8):3942-3946. 11513693
  3. Tunon, H., Olavsdotter, C., and Bohlin, L. Evaluation of anti-inflammatory activity of some Swedish medicinal plants. Inhibition of prostaglandin biosynthesis and PAF-induced exocytosis. J Ethnopharmacol1995;48(2):61-76. 8583796
  4. Di Mambro, V. M. and Fonseca, M. J. Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts. J Pharm Biomed Anal2-23-2005;37(2):287-295. 15708669
  5. Oberlies, N. H., Kim, N. C., Brine, D. R., Collins, B. J., Handy, R. W., Sparacino, C. M., Wani, M. C., and Wall, M. E. Analysis of herbal teas made from the leaves of comfrey (Symphytum officinale): reduction of N-oxides results in order of magnitude increases in the measurable concentration of pyrrolizidine alkaloids. Public Health Nutr2004;7(7):919-924. 15482618
  6. Schaneberg, B. T., Molyneux, R. J., and Khan, I. A. Evaporative light scattering detection of pyrrolizidine alkaloids. Phytochem Anal2004;15(1):36-39. 14979525
  7. Betz, J. M., Eppley, R. M., Taylor, W. C., and Andrzejewski, D. Determination of pyrrolizidine alkaloids in commercial comfrey products (Symphytum sp.).J Pharm Sci 1994;83(5):649-653. 8071814
  8. Kim, N. C., Oberlies, N. H., Brine, D. R., Handy, R. W., Wani, M. C., and Wall, M. E. Isolation of symlandine from the roots of common comfrey (Symphytum officinale) using countercurrent chromatography. J Nat Prod 2001;64(2):251-253. 11430014
  9. Gray, D. E., Porter, A., O’Neill, T., Harris, R. K., and Rottinghaus, G. E. A rapid cleanup method for the isolation and concentration of pyrrolizidine alkaloids in comfrey root. J AOAC Int2004;87(5):1049-1057. 15493660
  10. Ulubelen, A. and Doganca, S. Anadoline, a new senecio alkaloid from symphytum orientale. Tetrahedron Lett1970;30:2583-2585. 5448441
  11. Culvenor, C. C., Clarke, M., Edgar, J. A., Frahn, J. L., Jago, M. V., Peterson, J. E., and Smith, L. W. Structure and toxicity of the alkaloids of Russian comfrey (symphytum x uplandicum Nyman), a medicinal herb and item of human diet. Experientia4-15-1980;36(4):377-379. 7379906
  12. Barbakadze, V. V., Kemertelidze, E. P., Targamadze, I. L., Shashkov, A. S., and Usov, A. I. [Novel biologically active polymer of 3-(3,4-dihydroxyphenyl)glyceric acid from two types of the comphrey Symphytum asperum and S. caucasicvum (Boraginoceae)]. Bioorg Khim2002;28(4):362-366. 12197395
  13. Ahmad, V. U., Noorwala, M., Mohammad, F. V., and Sener, B. A new triterpene glycoside from the roots of Symphytum officinale. J Nat Prod1993;56(3):329-334. 8482944
  14. Franz, G. [Studies on the mucopolysaccharides of Tussilago farfara L., Symphytum officinalis L., Borago officinalis L. and Viola tricolor L]. Planta Med1969;17(3):217-220. 4241756
  15. Aftab, K., Shaheen, F., Mohammad, F. V., Noorwala, M., and Ahmad, V. U. Phyto-pharmacology of saponins from Symphytum officinale L. Adv Exp Med Biol1996;404:429-442. 8957312
  16. Mohammad, F. V., Noorwala, M., Ahmad, V. U., and Sener, B. A bidesmosidic hederagenin hexasaccharide from the roots of Symphytum officinale. Phytochemistry 1995;40(1):213-218. 7546550
  17. Noorwala, M., Mohammad, F. V., Ahmad, V. U., and Sener, B. A bidesmosidic triterpene glycoside from the roots of Symphytum officinale. Phytochemistry1994;36(2):439-443. 7764880
  18. Wagner, H., Horhammer, L., and Frank, U. [Lithospermic acid, the antihormonally active principle of Lycopus europaeus L. and Symphytum officinale. 3. Ingredients of medicinal plants with hormonal and antihormonal-like effect]. Arzneimittelforschung1970;20(5):705-713. 4193311
  19. Makarova, G. V. and et al. Farm Zh1966;21(5):41.
  20. Fijalkowski, D. and Seroczynska, M. Herba ol 1977;23:47.
  21. Furuya, T. and Araki, K. Studies on constituents of crude drugs. I. Alkaloids of Symphytum officinale Linn. Chem Pharm Bull (Tokyo)1968;16(12):2512-2516. 5719032
  22. Stamford, I. F. and Tavares, I. A. The effect of an aqueous extract of comfrey on prostaglandin synthesis by rat isolated stomach. J Pharm Pharmacol1983;35(12):816-817. 6141246
  23. Dolganiuc, A., Radu, L. D., and Olinescu, A. [The effect of products of plant and microbial origin on phagocytic function and on the release of oxygen free radicals by mouse peritoneal macrophages]. Bacteriol Virusol Parazitol Epidemiol1997;42(1-2):65-69. 1
  24. Brauchli, J., Luthy, J., Zweifel, U., and Schlatter, C. Pyrrolizidine alkaloids from Symphytum officinale L. and their percutaneous absorption in rats.Experientia 9-15-1982;38(9):1085-1087. 7128756

Izvor: www.sigmaaldrich.com

Symphytum officinale e radice (Symphytum) Bundesanzeiger Nr. 130 vom 17.7.1991

Monographie BGA/BfArM (Kommission D)

(Symphytum ad usum externum) Bundesanzeiger Nr. 130 vom 17.7.1991

Monographie BGA/BfArM (Kommission D)

Erscheinungsdatum Bundesanzeiger: 27.7.1990., Heftnummer: 138., ATC-Code: D11AG.
Monographie BGA/BfArM (Kommission E)

Comfrey herb and leaf (Symphyti herba/-folium) Published July 27, 1990.

List of German Commission E Monographs (Phytotherapy)












Pakovanje mL/ g:
 10 20 30 50 100 250 500 1000

Količina:
1 2 3 više 

 

 

vrh