• U PROŠLOSTI IZVOR ZDRAVLJA - U BUDUĆNOSTI IZVOR ZDRAVLJA •

2008-12-09T16:48:00.000-08:00

GINKGO BILOBA - BILJKA JE KOJA JE USPJELA PREŽIVJETI STOTINE MILIJUNA GODINA!!!!!! TO SE NIJE DOGODILO BEZ RAZLOGA!!!!!!!!!

KLIKNITE OVDJE I SAZNAJTE

MNOGO VIŠE!!!!!!!!

NO NA OVOJ STRANICI SAZNAT ĆETE VRLO MNOGO O LJEKOVITIM SVOJSTVIMA GINKGA BILOBE

ZA POČETAK EVO PRVO RAZNIH KEMIJSKIH FORMULA KOJE ĆEMO POSTEPENO OBJASNITI. ČEKA NAS VELIKI POSAO PA VAS MOLIM ZA STRPLJENJE - TIJEKOM SLIJEDEĆIH NEKOLIKO DANA OBJAVIT ĆEMO VELIKI DIO ONOGA ŠTO TREBAMO ZNATI O GINKGU BILOBI! - jer ne želimo pogreške!!!!!!!!!!!!!!

WHO

monografija o

selekciji

medicinskih - ljekovitih biljaka

__________

VOLUMEN 1

World Health Organization

Geneva

1999

(Originalna verzija uvoda – prijevod osnovnih pojmova o biti ove monografije: B. Begović)

WHO Library Cataloguing in Publication Data

WHO monographs on selected medicinal plants.—Vol. 1.

1.Plants, Medicinal 2.Herbs 3.Traditional medicine

ISBN 92 4 154517 8

(NLM Classification: QV 766)

The World Health Organization welcomes requests for permission to reproduce or translate itspublications, in part or in full. Applications and enquiries should be addressed to the Office ofPublications, World Health Organization, Geneva, Switzerland, which will be glad to provide thelatest information on any changes made to the text, plans for new editions, and reprints andtranslations already available.

The designations employed and the presentation of the material in this publication do not imply theexpression of any opinion whatsoever on the part of the Secretariat of the World Health Organizationconcerning the legal status of any country, territory, city or area or of its authorities, orconcerning the delimitation of its frontiers or boundaries.

The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of asimilar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

Typeset in Hong Kong

Printed in Malta

97/11795-Best-set/Interprint-6500

Sadržaj (Izdvojeno - ginkgo – ostalo originalna opcija)

Navedena monografija obuhvaća slijedeće pojmove-biljke (original)

Monografska obrada (abecednim redom – u originalu)

Bulbus Allii Cepae

Bulbus Allii Sativi

Aloe

Aloe Vera Gel

Radix Astragali

Fructus Bruceae

Radix Bupleuri

Herba Centellae

Flos Chamomillae

Cortex Cinnamomi

Rhizoma Coptidis

Rhizoma Curcumae Longae

Radix Echinaceae

Herba Echinaceae Purpureae

Herba Ephedrae

Folium Ginkgo

Radix Ginseng

Radix Glycyrrhizae

Radix Paeoniae

Semen Plantaginis

Radix Platycodi

Radix Rauwolfiae

Rhizoma Rhei

Folium Sennae

Fructus Sennae

Herba Thymi

Radix Valerianae

Rhizoma Zingiberis

Annex

Participants in the WHO Consultation on Selected Medicinal

Plants

Prilog

Sudionici za odabrane WHO konzultante o lijekovima

(U nastavku plavom bojom je predstavljena originalna i potpuna varijanta monografije ili samo pojedini važni fragmenti monografije!)

Zahvala

Posebna zahvala, zbog značajnog doprinosa na ovom projektu, profesorima Normanu R. Farnsworth, Harryu Rs Fong, i Gailu B. Mahady za suradnju sa WHO - Centrom za Traditional Medicin, College of Pharmacy, University of Illinois u Chicagu, SAD, za izradu i reviziju monografije. Navedeni ju također odobravaju i zahvaljuju članovima savjetodavne grupe koja se sastala u Pekingu, Kina, 1994. i sastavila popis ljekovitih biljaka za ovu monografiju koju je pripremilo više od 100 stručnjaka koji su dali komentare i savjete o nacrtu tekstova, a koji su sudjelovali u WHO konzultacijama, koje su se održavale u Münchenu, Njemačka, 1996. - sve do konačne varijante monografije (vidi Prilog - Annex) - Finally, WHO would like to thank the Food and Agriculture Organization of the United Nations and the United Nations Indus-trial Development Organization for their contributions and all those who submitted comments through the World Self-Medication Industry, a nongov-ernmental organization in official relations with WHO.

Uvod

Tijekom proteklih desetljeća, tradicionalni sustavi medicine postali su tema od globalne važnosti. Trenutne procjene sugeriraju da se veliki dio svjetske populacije snažno oslanja na tradicionalnu tehniku liječenja i ljekovito bilje što bi trebalo zadovoljiti (dopuniti) i potrebe primarne zdravstvene zaštite. Iako moderna medicina ne može uvijek biti dostupna u tim zemljama koje preferiraju ovakvu vrstu medicine, LJEKOVITO BILJE (phytomedicines) je često vezano uz popularizaciju iz povijesnih i kulturnih razloga. Usporedno tome, mnogi ljudi u razvijenim zemljama počeli su se baviti alternativnim ili komplementarnim terapijama, uključujući i ljekovito bilje. Nekoliko biljnih vrsta ljekovitih biljaka su znanstveno ocijenjene za svoje moguće uspješne medicinske primjene. Podataka (o pripravcima) o sigurnoj ljekovitosti i djelotvornosti kao lijeka imamo podatke za malo biljaka – njihovih ekstrata i njihovih aktivnih sastojaka. Nadalje, u većini zemalja u biljnoj mediteranskoj skupini tržište je slabo regulirano, i biljni proizvodi su često vrlo loše ili nikako regulirani – što se tiće pravila WHO-a. Osiguranje sigurnosti, kvalitete i učinkovitosti medicinskog bilja i biljnih proizvoda je trenutno postao ključni problem u industrijaliziranim zemljama i zemljama u razvoju. Oba potrošaća trebaju od kompetentnih osoba (profesora i doktora medicine, botanike i dr. znanstvenika) dobiti mišljenja i studije, te autoritativne informacije o sigurnosti i učinkovitost ljekovitih biljaka. Tijekom četvrte Međunarodne konferencije o drogama-lijekovima (ICDRA) održane u Tokyu 1986., zatražen je popis ljekovitih biljaka te da se uspostavi međunarodna specifikacija za većinu naširoko koristećih ljekovitih biljaka koje se jednostavno pripremaju. Smjernice za uporabu ljekovitih biljaka za biljne lijekove je naknadno pripremila WHO i usvojila na šestom ICDRA u Ottawi, Kanada, 1991. (Guidelines for the assessment of herbal medicines. In: Quality assurance of pharmaceuticals: a compendium of guidelines and related materials. Volume 1. Geneva, World Health Organization, 1997:31–37.)

Kao rezultat ICDRA-ove preporuke i kao odgovor na zahtjeve iz država članica ove skupine - u pružanju pomoći za sigurne i učinkovite biljne lijekovite preparate za uporabu nacionalnih zdravstvenih sustava, u ovom (1) dijelu izdvojeno je i uvršteno 28 odabranih ljekovitih biljaka, a druge su u pripremi za isto.

Priprema za monografiju

Ljekovite biljke sadržane u ovoj monografiji su odabrane prema savjetodavnoj stručnoj skupini koja je radila protekle četiri godine – od 1994.

The medicinal plants featured in this volume were selected by an advisory group in Beijing in 1994. The plants selected are widely used and important in all WHO regions, and for each sufficient scientific information seemed available to substantiate safety and efficacy. The monographs were drafted by the WHO Collaborating Centre for Traditional Medicine at the University of Illinois at Chicago, United States of America. The content was obtained by a systematic review of scientific literature from 1975 until the end of 1995: review articles; bibliographies in review articles; many pharmacopoeias—the International, African, British, Chinese, Dutch, European, French, German, Hungarian, Indian, and Japanese; as well as many other reference books. Draft monographs were widely distributed, and some 100 experts in more than 40 countries commented on them. Experts included members of WHO's Expert Advisory Panels on Traditional Medicine, on the International Pharmacopoeia and Pharmaceutical Preparations, and on Drug Evaluation and National Drug Policies; and the drug regulatory authorities of 16 countries. A WHO Consultation on Selected Medicinal Plants was held in Munich, Germany, in 1996. Sixteen experts and drug regulatory authorities from Member States participated. Following extensive discussion, 28 of 31 draft monographs were approved. The monograph on one medicinal plant was re-jected because of the plant's potential toxicity. Two others will be reconsidered when more definitive data are available. At the subsequent eighth ICDRA in Bahrain later in 1996, the 28 model monographs were further reviewed and endorsed, and Member States requested WHO to prepare additional model monographs.

Svrha i sadržaj monografije

Svrha ove monografije je:

pružiti znanstvene informacije o sigurnosti, djelotvornosti i kontroli kvalitete / Osiguranje stupnja kvalitete ljekovitog bilja, kako bi se olakšala njihova odgovarajuća primjena u državama članicama; osigurati pomoć državama članicama u razvoju vlastitog odnosa prema biljnim lijekovima, i olakšati razmjenu informacija između država članica.

Readers will include members of regulatory authorities, practitioners of orthodox and of traditional medicine, pharmacists, other health professionals, manu-facturers of herbal products, and research scientists.

Each monograph contains two parts. The first part consists of pharmacopoeial summaries for quality assurance: botanical features, distribution, identity tests, purity requirements, chemical assays, and active or major chemical constituents. The second part summarizes clinical applications, pharmacology, contraindications, warnings, precautions, potential adverse reactions, andposology.

In each pharmacopoeial summary, the Definition section provides the Latin binomial pharmacopoeial name, the most important criterion in quality assurance. Latin pharmacopoeial synonyms and vernacular names, listed in the sections Synonyms and Selected vernacular names, are those names used in com-merce or by local consumers. The monographs place outdated botanical nomenclature in the synonyms category, based on the International Rules of Nomenclature.

For example, Aloe barbadensis Mill. is actually Aloe vera (L.) Burm. Cassia acutifolia Delile and Cassia angustifolia Vahl., often treated in separate monographs, are now believed to be the same species, Cassia senna L. Matricaria chamomilla L., M. recutita L., and M. suaveolens L. have been used for many years as the botanical name for camomile. However, it is now agreed that the name Chamomilla recutita (L.) Rauschert is the legitimate name.

The vernacular names listed are a selection of names from individual countries worldwide, in particular from areas where the medicinal plant is in common use. The lists are not complete, but reflect the names appearing in the official monographs and reference books consulted during preparation of the WHO monographs and in the Natural Products Alert (NAPRALERT) database (a database of literature from around the world on ethnomedical, biological and chemical information on medicinal plants, fungi and marine organisms, located at the WHO Collaborating Centre for Traditional Medicine at the University of Illinois at Chicago).

A detailed botanical description (under Description) is intended for quality assurance at the stages of production and collection, whereas the detailed description of the drug material (under Plant material of interest) is for the same purpose at the manufacturing and commerce stages. Geographical distribution is not normally found in official compendia, but it is included here to provide additional quality assurance information.

General identity tests, Purity tests, and Chemical assays are all normal compendial components included under those headings in these monographs. Where purity tests do not specify accepted limits, those limits should be set in accordance with national requirements by the appropriate Member State authorities.

Each medicinal plant and the specific plant part used (the drug) contain active or major chemical constituents with a characteristic profile that can be used for chemical quality control and quality assurance. These constituents are described in the section Major chemical constituents.

The second part of each monograph begins with a list of Dosage forms and of Medicinal uses categorized as those uses supported by clinical data, those uses described in pharmacopoeias and in traditional systems of medicine, and those uses described in folk medicine, not yet supported by experimental or clinical data.

The first category includes medical indications that are well established in some countries and that have been validated by clinical studies documented in the world's scientific literature. The clinical trials may have been controlled, randomized, double-blind studies, open trials, or well-documented observations of therapeutic applications. Experts at the Munich Consultation agreed to include Folium and Fructus Sennae, Aloe, Rhizoma Rhei, and Herba Ephedrae in this category because they are widely used and their efficacy is well documented in the standard medical literature.

The second category includes medicinal uses that are well established in many countries and are included in official pharmacopoeias or national monographs. Well-established uses having a plausible pharmacological basis and supported by older studies that clearly need to be repeated are also included. The references cited provide additional information useful in evaluating specific herbal preparations. The uses described should be reviewed by local experts and health workers for their applicability in the local situation.

The third category refers to indications described in unofficial pharma-copoeias and other literature, and to traditional uses. The appropriateness of these uses could not be assessed, owing to a lack of scientific data to support the claims. The possible use of these remedies must be carefully considered in the light of therapeutic alternatives.

The final sections of each monograph cover Pharmacology (both experimental and clinical); Contraindications such as sensitivity or allergy; Warnings; Precautions, including discussion of drug interactions, carcinogenicity, teratogenicity and special groups such as children and nursing mothers; Adverse reactions; and Posology.

Use of the monographs

WHO encourages countries to provide safe and effective traditional remedies and practices in public and private health services.

This publication is not intended to replace official compendia such as pharmacopoeias, formularies, or legislative documents. The monographs are intended primarily to promote harmonization in the use of herbal medicines with respect to levels of safety, efficacy, and quality control. These aspects of herbal medicines depend greatly on how the individual dosage form is pre-pared. For this reason, local regulatory authorities, experts, and health workers, as well as the scientific literature, should be consulted to determine whether a specific herbal preparation is appropriate for use in primary health care.

The monographs will be supplemented and updated periodically as new information appears in the literature, and additional monographs will be prepared. WHO would be pleased to receive comments and suggestions, to this end, from readers of the monographs.

Finally, I should like to express our appreciation of the support provided for the development of the monographs by Dr H. Nakajima and Dr F. S. Antezana during their time as Director-General and Assistant Director-General, respectively, of WHO.

Dr Xiaorui Zhang

Medical Officer

Traditional Medicine

World Health Organization

Svjetska zdravstvena organizacija (WHO)

List ginkgo Folium Ginkgo

Definicija

List ginkga se sastoji od osušenog cijelog lista ginkgo biloba L. (Ginkgoaceae).

Sinonimi

Pterophyllus salisburiensis Nelson, Salisburia adiantifolia Smith, Salisburia macrophylla C. Koch (1-4).

Odabrani kolokvijalni nazivi

Eun-haeng, gin-nan, ginkgo, ginkgo matičnjak, ginkyo, ginan, icho, ityo, kew drvo, stablo viline vlasi, pei-wen, hramsko stablo, yin guo, yinhsing (1-5).

Opis

Dvodomna biljka koja je jedini živi predstavnik porodice Ginkgoales. Kora stabla je siva, doseže visinu od 35 m, a promjera 3-4 m (ponekad i do 7 m), lišće otpada kao u bjelogorice, dvorežnjasto je, osnovni oblik lepezast, 6-9 cm širok (ponekad 15-20 cm), u jesen list žute boje. Žilice lista paralelno se granaju. Muški pokretljivi spermiji oplođuju ženska jaja. Rezultat: plod oštrog i jakog mirisa u kojem je jedna koštunica. Vanjski sloj mesnat. Zrelo sjemenje žućkaste boje, a suho sjeme vrlo tvrdo.

A monotypic dioecious plant that is the only living representative of the Ginkgoales. It has a grey bark, reaches a height of 35 m and a diameter of 3–4 m (sometimes up to 7 m), and has fan-like leaves that are deciduous, alternate, lengthily petiolate, bilobate, base wedge-shaped, 6–9 cm broad (sometimes up to 15–20 cm), turning yellow in autumn. Venation dichotomously branching, seemingly parallel. Staminate and ovulate strobili borne on separate trees; staminate strobili consisting of naked pairs of anthers in catkin-like clusters; ovulate strobili in the form of long, slender, fused stalks bearing a single naked ovule which is fertilized by motile sperm cells, developing into 2 seeds. Seeds yellow when mature, foul-smelling, drupe-like, the middle layer of integument becoming hard or stone-like, the outer layer fleshy (3, 4).

Važan biljni materijal: osušeni list

Koštica (kao orah - sjeme) koja se koristi u kineskoj medicini (6, 7).

Opći izgled

U vegetaciji list je zelen, zatim sivo-žut, te smeđi ili crnkast; gornja strana lista uglavnom je nešto tamnija nego donja. U biti na dužoj peteljci nalazi se list koji se sastoji od dva dijela sličnih lepezi (2, 4, 8).

Organoleptička svojstva

Ginkgo nema posebno karakterističan miris – list (2, 4, 8).

Mikroskopski karakteristike

Mladi listovi imaju izobilje krvotočnih žilica, dok lišće nema srednje rebro, a list ispunjavaju paralelne žilice koje nemaju bazu, međutim sve počinje od peteljke.

While the leaves have no midrib, dichotomous venation with regular, numerous branching parallel veins arises from two vascular strands within the petiole. Stomata occur almost exclusively on the lower surface of the leaf. The epidermis of the upper and underside of the leaf consists of undulated, irregular, mostly long extended cells. In the cross-section, the epidermal cells appear nearly isodiametric and from above appear to be slightly undulated, with the upper cells appearing larger. The outer walls of the epider-mal cells are covered with a more or less thin layer of cuticle. In the area of vascular bundles there are remarkable long extended narrow cells with slightly undulated walls. Numerous druses of calcium oxalate occur near the vascular bundles (2, 4).

Biljni materijal u prahu

Boja praha suhog lista identična je boji lišća.

The powder shows fragments of the epidermis with wavelike indentations irregular in form with generally elongated cells; large stomal openings of the anisocytic type; mark-edly elongated, narrow cells with only weakly undulated walls in the vascular areas and without marked indentations. The equifacial mesophyll comprises excretory vesicles, secretory cells, and idioblasts, as well as intermittent calcium oxalate druses, in the region of the vascular fascicles (2, 8).

Geografsko podrijetlo

Postojbina u Kini, ali raste kao ukrasno stablo u Australiji, jugoistočnoj Aziji, Europi, Japanu i Sjedinjenim Američkim Državama (1-3, 6). Komercijalno se najviše uzgaja u Francuskoj i Sjedinjenim Američkim Državama (2).

Identifikacijske testovne osnove

Opći i mikroskopski pregled (2, 8). Analizom potvrđena prisutnost: flavonoidi, ginkgolidi i bilobalidi (9), visoke performanse tekućina kromatografske analize za: flavonoidi (10), ginkgolidi i bilobalidi (2); i evaluacija od ginkgolida i bilobalida (11).

Testovi

Mikrobiologija

Test na salmonele spp. u listu ginkga je negativan. MAXI-mama je prihvatljivih granica kao i drugih mikroorganizama - kako slijedi (12-14). Za priprema esencije: aerobna bakterija - ne više od 107 / g, gljive - ne više od 105 / g, Escherichia coli - ne više od 102 / g. Pripreme za internu uporabu: aerobna bakterija - ne više od 105 / g ili ml; gljive-ne više od 104 / g ili ml; enterobakterije i neke gram - negativne bakterije - ne više od 103 / g ili ml; Escherichia coli-0 / g ili ml.

Strane organske tvari

Ne više od 5% neštetnih tvari i ne više od 2% drugih stranih tvari (15).

Ukupno pepeo

Ne više od 11% (15).

Pesticidi

Da bi bio u skladu s internacionalno prihvatljivim zahtjevima. Uobičajeno je maksimalno ograničenje ostataka aldrina i dieldrina u listu ginkga ne više od 0,05 mg / kg (14). Za druge pesticide, vidjeti upute za kontrolu kvalitete za ljekovito bilje (12), i smjernice za predviđanje unosa od ostataka pesticida (16).

Teški metali

Preporučena razina olova i kadmija ne smije biti veća od 10 i 0.3mg/kg, odnosno, doza u konačnom obliku je biljni materijal (12).

Recommended lead and cadmium levels are not more than 10 and 0.3mg/kg,

respectively, in the final dosage form of the plant material (12).

Radioaktivni ostaci

Za analizu – stroncija - 90, jod - 131, cezij - 134, cezija - 137 i plutonij - 239, kao kod opće kontrole kvalitete ljekovitog bilja (12).

Ostali testovi čistoće

Kiseline.........i dr. u skladu s nacionalnim zahtjevima.

Acid-insoluble ash, acid-insoluble extractive, chemical, and moisture tests to be established in accordance with national requirements.

Kemijski sastojci - mjere

Flavonoidi ne manje od 0,5% - obračunava se kao flavonol glikozida 0.2-0.4% - izračunava se kao aglycones (17), također sadrži ginkgolida (0.06-0.23%) i bilobalida (do 0,26%) (2, 17). Kvalitativna i kvantitativna određivanja flavonoidglikozida je provedena (nakon hidrolize) na glycones kemferovo ulje, kvercetin, a izoramnetin. Za kvalitetu određuje se prisutnost ili odsutnost biflavona (17); i kvalitativna i kvantitativna sadržajnost ginkgolida i sesquiterpen bilobalida (2, 18), ( 11).

Neki komercijalni proizvodi koriste se za kliničke i eksperimentalne biološke studije, npr. EGb LI 761 i 1370, koji ne sadrže biflavone.

Flavonoids not less than 0.5% calculated as flavonol glycosides or 0.2–0.4% calculated as aglycones (17); also contains ginkgolides (0.06–0.23%) and bilobalide (up to 0.26%) (2, 17).

Qualitative and quantitative determination of flavonoid glycosides is carried out after hydrolysis to the aglycones kaempferol, quercetin, and isorhamnetin. The qualitative presence or absence of biflavones (17) is determined by high-performance liquid chromatography; and qualitative and quantitative deter-mination of the diterpene ginkgolides and sesquiterpene bilobalide by high-performance liquid chromatography (2, 18) or gas–liquid chromatography (11).

Certain commercial products used for clinical and experimental biological studies, e.g. EGb 761 and LI 1370, do not contain biflavones.

Značajke kemijskih konstituenata

List ginkgo sadrži raznovrsnu fitokemiju. Tu su uključeni alkani, lipidi, steroli, benzenoidi, karotenoidi, fenilpropani, ugljikohidrati, flavonoidi i terpenoli (18, 19). U glavnini su flavonoidi. Karakteristični sastojak ovog biljnog materijala su jedinstveni ginkgolidi A, B, C, J i M i sesquiterpen lakton bilobalidi (17).

Folium Ginkgo contains a wide variety of phytochemicals, including alkanes, lipids, sterols, benzenoids, carotenoids, phenylpropanoids, carbohydrates, flavonoids, and terpenoids (18, 19). The major constituents are flavonoids of which mono-, di-, and tri-glycosides and coumaric acid esters that are based on the flavonols kaempferol and quercetin dominate. Lesser quantities of glyco-sides are derived from isorhamnetin, myricetin, and 3'-methylmyricetin. Non-glycosidic biflavonoids, catechins, and proanthocyanidins are also present (15).

Characteristic constituents of this plant material are the unique diterpene lactones ginkgolides A, B, C, J, and M and the sesquiterpene lactone bilobalide (17). Representative structures of the major and characteristic constituents are presented below.

Oblici doziranja

Standardizirani ekstrati (suhi ekstrati iz osušeni listovi, izdvojen sa acetonom i vodom, droga (lijek): ekstrat omjer 35-67: 1) sadrži 22-27% flavonglikozida i 5-7% terpenlactona, od kojih oko 2.8-3.4% čine ginkgolidi A, B i C i 2.6-3.2% bilobalidi. Razina ginkgolidne kiseline je ispod 5 mg / kg. Ovo je sadržaj ekstrata koji se unosi u organizam putem tableta (20, 21).

Ljekovitost

Ljekovitost je podržana od strane kliničkih podataka. Ekstrakt (doziranje) je kako je gore opisan (doziranje - oblici) su korišteni za simptomatično liječenje blage do umjerene cerebrovaskularne nedostatnosti (u osnovi degenerativne demencije, vaskularne demencije, i mješoviti oblici oba) sa sljedećim simptomima: manjak memorije, poremećaj u koncentraciji, depresivna emocionalna stanja, vrtoglavica, zujanje u ušima, glavobolja (1, 3, 20-22)...

Extracts as described above (Dosage forms) have been used for symptomatic treatment of mild to moderate cerebrovascular insufficiency (demential syn-dromes in primary degenerative dementia, vascular dementia, and mixed forms of both) with the following symptoms: memory deficit, disturbance in concen-tration, depressive emotional condition, dizziness, tinnitus, and headache (1, 3, 20–22). Such extracts are also used to improve pain-free walking distance in people with peripheral arterial occlusive disease such as intermittent claudication, Raynaud disease, acrocyanosis, and post-phlebitis syndrome, and to treat inner ear disorders such as tinnitus and vertigo of vascular and involutive origin (20, 23–27). Extracts and doses other than those described in Dosage forms and Posology are used for similar but milder indications (28, 29).

Opisanih koristi u farmaceutskim i tradicionalnim medicinskim sistemima

Nema.

Opisane koristi u narodnoj medicini - ne podržavaju eksperimentalne kliničke podatke

As a vermifuge, to induce labour, for the treatment of bronchitis, chronic rhinitis, chilblains, arthritis, and oedema (3, 5).

Farmakologija

Eksperimentalna farmakologija

Cerebrovaskularna oštećenja i periferne vaskularne bolesti

.......... In vitro istraživanja su pokazala da G. biloba ekstrat djeluje protiv aktivnih radikala (33-37). ......Miševi tretirani s standardiziranim ekstratom G. biloba (100 mg / kg, oralno za 4-8 tjedna) - pokazalo je poboljšanje memorije i brže učenje ..... (64).

In vitro studies. A standardized extract of Ginkgo biloba (100 µg/ml) did not produce isometrically recordable contractions in isolated rabbit aorta but did potentiate the contractile effect of norepinephrine (30). Higher concentrations (EC50 ? 1.0 mg/ml) produced a concentration-dependent contraction that could be antagonized by the α-adrenoceptor-blocking agent phentolamine (30). Both cocaine and desipramine, inhibitors of catecholamine reuptake, potentiated the contractile effect of norepinephrine but inhibited the contractile effects of a standardized extract of G. biloba and tyramine (30). The results of these experi-ments indicate that the contractile action of G. biloba may be due to the release of catecholamines from endogenous tissue reserves, and this activity may explain some of the therapeutic effects of the drug in humans (e.g. improve-ment in cerebrovascular and peripheral vascular insufficiency) (1, 30). On the basis of experiments comparing the effects of an extract of G. biloba, phentolamine, propranolol, gallopamil, theophylline, and papaverine on the biphasic contractile response of norepinephrine in isolated rat aorta, researchers concluded that G. biloba had musculotropic action similar to that of papaverine (31). This activity was previously reported for the flavonoids quercetin, kaempferol, and isorhamnetin, isolated from the leaves of G. biloba (32). The flavonoids and papaverine both inhibit 3',5' -cyclic-GMP phosphodiesterase, which in turn induces endothelium-dependent relaxation in isolated rabbit aorta by potentiating the effects of endothelium-derived relaxing factors (1).

In vitro studies have demonstrated that G. biloba extracts scavenge free radicals (33–37). Ginkgo biloba extracts have been reported to reduce free radical-lipid peroxidation induced by NADPH-Fe3+ systems in rat microsomes (33), and to protect human liver microsomes from lipid peroxidation caused by ciclosporin A (34). The extract also inhibits the generation of reactive oxygen radicals in human leukocytes treated with phorbol myristate acetate (35). The antioxidant action of G. biloba extract may prolong the half-life of endothelium-derived relaxing factor by scavenging superoxide anions (36, 37). Both the flavonoid and terpenoid constituents of G. biloba appear to aid the free-radical scavenging activity of the drug (37).

Ginkgo biloba extract protected against brain tissue hypoxic damage in vitro. The ginkgolides and bilobalide were responsible for the antihypoxic activity of the extract (38, 39). Ginkgolides A and B have been shown to protect rat hippocampal neurons against ischaemic damage, which may be due to their ability to act as antagonists to receptors for platelet-activating factor (PAF) (40–42).

In vivo studies. Oral administration of G. biloba extract protected rats against induced cerebral ischaemia (43–45). Intravenous perfusion of a G. biloba extract prevented the development of multiple cerebral infarction in dogs injected with fragments of an autologous clot into a common carotid artery (46). These data suggest that G. biloba extract, administered after clot formation, may have some beneficial effects on acute cerebral infarction or ischaemia caused by embolism (1). Other experiments demonstrated that animals treated with G. biloba extract survived under hypoxic conditions longer than did untreated controls (47, 48). Longer survival was due not only to significant improvements in cerebral blood flow, but also to an increase in the level of glucose and ATP (44, 48–50). Other studies have shown that a G. biloba extract devoid of ginkgolides but containing bilobalide had protective activity when administered intraperitoneally to mice with induced hypobaric hypoxia (51, 52). Intravenous infusion of G. Biloba extract significantly increased pial arteriolar diameter in cats (53) and improved cerebral blood flow in rats (53). The active constituents of G. biloba responsible for increasing cerebral blood flow appeared to be the non-flavonoid compounds (54); ginkgolide B may be responsible for this action owing to its PAF-antagonist activity (55, 56). Furthermore, intravenous administration of a standardized G. biloba extract and ginkgolide B to rats showed that the extract, but not ginkgolide B, decreased the brain's use of glucose (57).

The constituents of G. biloba responsible for its anti-ischaemic activity re-main undefined. The flavonoids, ginkgolides, and bilobalide have all been sug-gested, but it is possible that other constituents may be responsible. An extract of G. biloba was effective in the in vivo treatment of cerebral oedema, a condition of excessive hydration of neural tissues owing to damage by neurotoxic agents (such as triethyltin) or trauma (58–60). Bilobalide appeared to play a significant role in the antioedema effect (61, 62). Oral or subcutaneous administration of an extract of G. biloba to rats with acute and chronic phases of adriamycin-induced paw inflammation partially reversed the increase in brain water, sodium, and calcium and the decrease in brain potassium associated with sodium arachidonate-induced cerebral infarction (63).

Mice treated with a standardized extract of G. biloba (100 mg/kg, orally for 4–8 weeks) showed improved memory and learning during appetitive operant conditioning (64).

Vestibularni i slušni efekti - djelovanje Gbe

Ginkgo biloba ekstrat pozitivno je djelovao na vestibularni i slušni sustav nakon eksperimentiranja na miševima, štakorima i mačkama.......

Ginkgo biloba extract improved the sum of action potentials in the cochlea and acoustic nerve in cases of acoustically produced sound trauma in guinea-pigs (1, 65). The mechanism reduced the metabolic damage to the cochlea. Oral or parenteral administration of a standardized G. biloba extract to mice (2 mg/kg) improved the ultrastructure qualities of vestibular sensory epithelia when the tissue was fixed by vascular perfusion (66). Improvement was due to the effects of the drug on capillary permeability and general microcirculation (1, 66).

Positive effects on vestibular compensation were observed after administration of G. biloba extract (50 mg/kg intraperitoneally) to rats and cats that had undergone unilateral vestibular neurectomy (67, 68).

Antagonizam trombocita-aktivirajući faktor (PAF)

Ginkgolidi, a posebice ginkgolid B, poznat je kao pokretać trombocita...

The ginkgolides, and in particular ginkgolide B, are known antagonists of PAF (69–73). PAF is a potent inducer of platelet aggregation, neutrophil degranu-lation, and oxygen radical production leading to increased microvascular per-meability and bronchoconstriction. Intravenous injections of PAF induced transient thrombocytopenia in guinea-pigs, which was accompanied by non-histamine-dependent bronchospasm (69, 70). Ginkgolide B has been shown to be a potent inhibitor of PAF-induced thrombocytopenia and bronchocon-striction (71, 72). PAF or ovalbumin-induced bronchoconstriction in sensitized guinea-pigs was inhibited by an intravenous injection of ginkgolide B (1–3mg/kg) 5 minutes prior to challenge (73).

Klinička farmakologija

Cerebralne nedostatnosti

Cerebralna nedostatnost nije potpuno egzaktan pojam za opisivanje prikupljenih simptoma povezanih s demencijom – padom intelektualnih sposobnosti, no pokazalo se da Gbe pozitivno djeluje na tu vrstu oboljenja tj: poteškoće u koncentraciji i pamćenju, odsutnosti duha, konfuziju, nedostatak energije, umor, smanjene fizičke performanse, depresivna raspoloženja, anksioznost, vrtoglavicu, zujanje u ušima, glavobolju....

Cerebral insufficiency is an inexact term to describe a collection of symptoms associated with dementia (21, 22). In dementia owing to degeneration with neuronal loss and impaired neurotransmission, decline of intellectual function is associated with disturbances in the supply of oxygen and glucose. In clinical studies G. biloba effectively managed symptoms of cerebral insufficiency including difficulty in concentration and memory, absent-mindedness, confusion, lack of energy, tiredness, decreased physical performance, depressive mood, anxiety, dizziness, tinnitus, and headache (20–22). Several mechanisms of action of G. biloba have been described: effects on blood circulation such as the vasoregulating activity of arteries, capillaries, veins (increased blood flow); rheological effects (decreased viscosity, by PAF-receptor antagonism); metabolic changes such as increased tolerance to anoxia; beneficial influence on neurotransmitter disturbances; and prevention of damage to membranes by free radicals (22). Treatment of humans with G. biloba extract has been shown to improve global and local cerebral blood flow and microcirculation (74–76), to protect against hypoxia (77), to improve blood rheology, including inhibition of platelet aggregation (74, 78–81), to improve tissue metabolism (82), and to reduce capillary permeability (83).

A critical review of 40 published clinical trials (up to the end of 1990) using an orally administered G. biloba extract in the treatment of cerebral insufficiency concluded that only eight of the studies were well performed (21, 22). Almost all trials reported at least a partially positive response at dosages of 120–160mg a day (standardized extract) and treatment for at least 4–6 weeks (21, 22). In a comparison of G. biloba with published trials using co-dergocrine

(dihydroergotoxine), a mixture of ergoloid mesilates used for the same purpose, both G. biloba extract and co-dergocrine showed similar efficacy. A direct comparison of 120mg of G. biloba standardized extract and 4.5 mg co-dergocrine showed similar improvements in both groups after 6 weeks (84).

A meta-analysis of 11 placebo-controlled, randomized double-blind studies in elderly patients given G. biloba extract (150 mg orally per day) for cerebral insufficiency concluded that eight studies were well performed (85). Significant differences were found for all analysed single symptoms, indicating the superiority of the drug in comparison with the placebo. Analysis of the total score of clinical symptoms indicated that seven studies confirmed the effectiveness of G. biloba extract, while one study was inconclusive (85).

Periferne arterijske bolesti

Nakon kontroliranih pokusa sa bolesnicima s perifernim arterijskim bolestima 1990. godine g. biloba ekstrat kod tih bolesnika djelovao je vrlo pozitivno i ostvaren je značajan pozitivan terapijski učinak.

The effectiveness of G. biloba extract in the treatment of intermittent claudication (peripheral arterial occlusive disease Fontaine stage II), as com-pared with a placebo, was demonstrated in placebo-controlled, double-blind clinical trials by a statistically significant increase in walking distance (1, 23, 24).

Sixty patients with peripheral arterial occlusive disease in Fontaine stage Iib who were treated with the drug (120–160mg for 24 weeks) and underwent physical training also clearly increased their walking distance (25).

Out of 15 controlled trials (up to the end of 1990) only two (23, 24) were of acceptable quality (22–24). The results of both studies were positive and showed an increase in walking distance in patients with intermittent claudication after 6 months (23), and an improvement of pain at rest in patients treated with 200 mg of G. biloba extract for 8 weeks (24).

After meta-analysis of five placebo-controlled clinical trials (up to the end of 1991) of G. biloba extract in patients with peripheral arterial disease, investigators concluded that the extract exerted a highly significant therapeutic effect (26).

Vrtoglavica i zujanje u ušima

Ginkgo biloba ekstrati su korišteni su u liječenju centralnog uha, tj. bolesti kao što su nagluhost, vrtoglavica i zujanje u ušima. Primjenom GBe na stotinjak pacijenata javilo se znatno poboljšanje.

Ginkgo biloba extracts have been used clinically in the treatment of inner ear disorders such as hearing loss, vertigo, and tinnitus. In a placebo-controlled, double-blind study of 68 patients with vertiginous syndrome of recent onset, treatment with G. biloba extract (120–160mg daily, for 4–12 weeks) produced a statistically significant improvement as compared with the placebo group

(27).

The results of clinical studies on the treatment of tinnitus have been contradictory. At least six clinical studies have assessed the effectiveness of G. Biloba extract for the treatment of tinnitus. Three studies reported positive results (86, 87, 88). One multicentre, randomized, double-blind, 13-month study of 103 patients with tinnitus showed that all patients improved, irrespective of the prognostic factor, when treated with G. biloba extract (160 mg/day for 3 months) (86). Three other clinical trials reported negative outcomes (89–91).

Statistical analysis of an open study (80 patients) without placebo, coupled with a double-blind, placebo-controlled part (21 patients), demonstrated that a con-centrated G. biloba extract (29.2 mg/day for 2 weeks) had no effect on tinnitus (91).

Kontraindikacije

Hipersenzitivnost G. biloba praparata (20).

Hypersensitivity to G. biloba preparations (20).

Upozorenja

Nema dostupnih informacija.

Mjere opreza

Karcinogeneza, mutageneza, smanjenje plodnosti.

Carcinogenesis, mutagenesis, impairment of fertility

Investigations with G. biloba extracts have shown no effects that were mu-tagenic, carcinogenic, or toxic to reproduction (20).

Trudnoća: nisu značajno proučavani i dokazani popratni efekti

The safety of Folium Ginkgo for use during pregnancy has not been established.

Majka-dojilja

Izlučivanje iz lista ginkga u mlijeko i utjecaj na novorođenče – nema podataka o popratnim efektima, nije ustanovljeno.

Excretion of Folium Ginkgo into breast milk and its effects on the newborn have not been established.

Ostale mjere opreza

Nema posebnih informacija.

No information is available concerning general precautions or drug interactions, drug and laboratory test interactions, teratogenic effects on pregnancy, or paediatric use.

Nepovoljne reakcije

Glavobolje, gastrointestinalni poremećaji, moguće su alergijske reakcije na koži.

Headaches, gastrointestinal disturbances, and allergic skin reactions are possible adverse effects (20).

Doziranje-omjeri

Osušeni ekstrat (kao što je opisano u doziranju), 120-240 mg dnevno u 2 ili 3 podijeljene doze (2), 40 mg ekstrata je ekvivalent za 1,4-2,7 g listova (20). Fluid ekstrat (1:1), 0,5 ml 3 puta dnevno (1, 2).

Reference (literatura)

1. DeFeudis FV. Ginkgo biloba extract (egb 761): pharmacological activities and clinical

applications. Paris, Elsevier, Editions Scientifiques, 1991:1187.

2. Hänsel R et al., eds. Hagers Handbuch der pharmazeutischen Praxis, Vol. 6, 5th ed.

Berlin, Springer-Verlag, 1994.

3. Squires R. Ginkgo biloba. Australian traditional medicine society (ATOMS), 1995:9–14.

4. Huh H, Staba EJ. The botany and chemistry of Ginkgo biloba L. Journal of herbs, spices and medicinal plants, 1992, 1:91–124.

5. Farnsworth NR, ed. NAPRALERT database. University of Illinois at Chicago, IL,

August 8, 1995 production (an on-line database available directly through the

University of Illinois at Chicago or through the Scientific and Technical Network

(STN) of Chemical Abstracts Services).

6. Keys JD. Chinese herbs, their botany, chemistry and pharmacodynamics. Rutland,

VT, CE Tuttle, 1976:30–31.

7. Pharmacopoeia of the People's Republic of China (English ed.). Guangzhou, Guangdong Science and Technology Press, 1992:64.

8. Melzheimer V. Ginkgo biloba L. aus Sicht der systematischen und angewandten

Botanik. Pharmazie in unserer Zeit, 1992, 21:206–214.

9. Van Beek TA, Lelyveld GP. Thin layer chromatography of bilobalide and ginkgolides

A, B, C and J on sodium acetate impregnated silica gel. Phytochemical analysis, 1993,

4:109–114.

10. Hasler A, Meier B, Sticher O. Identification and determination of the flavonoids from

Ginkgo biloba by HPLC. Journal of chromatography, 1992, 605:41–48.

11. Hasler A, Meier B. Determination of terpenes from Ginkgo biloba by GLC. Pharmacy

and pharmacology letters, 1992, 2:187–190.

12. Quality control methods for medicinal plant materials. Geneva, World Health Organiza-tion, 1998.

13. Deutsches Arzneibuch 1996. Vol. 2. Methoden der Biologie. Stuttgart, Deutscher

Apotheker Verlag, 1996.

14. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1997.

15. Sticher O. Biochemical, pharmaceutical and medical perspectives of Ginkgo prepara-tions. In: New Drug Development from Herbal Medicines in Neuropsychopharmacology.

Symposium of the XIXth CINP Congress, Washington, DC, June 27–July 1, 1994.

16. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva,

World Health Organization, 1997 (unpublished document WHO/FSF/FOS/97.7;

available from Food Safety, WHO, 1211 Geneva 27, Switzerland).

17. Sticher O. Quality of Ginkgo preparations. Planta medica, 1993, 59:2–11.

18. Van Beek TA et al. Determination of ginkgolides and bilobalide in Ginkgo biloba

leaves and phytochemicals. Journal of chromatography, 1991, 543:375–387.

19. Hasler A et al. Complex flavonol glycosides from the leaves of Ginkgo biloba.

Phytochemistry, 1992, 31:1391.

20. German Commission E monograph, Trockenextrakt (35–67: 1) aus Ginkgo-biloba-Blättern Extrakt mit Aceton-Wasser. Bundesanzeiger, 1994, 46:7361–7362.

21. Kleijnen J, Knipschild P. Ginkgo biloba. Lancet, 1992, 340:1136–1139.

22. Kleijnen J, Knipschild P. Ginkgo biloba for cerebral insufficiency. British journal of

clinical pharmacology, 1992, 34:352–358.

23. Bauer U. Six month double-blind randomized clinical trial of Ginkgo biloba extract

versus placebo in two parallel groups in patients suffering from peripheral arterial

insufficiency. Arzneimittel-Forschung, 1984, 34:716–720.

24. Saudreau F, Serise JM, Pillet J. Efficacité de l'extrait de Ginkgo biloba dans le

traitement des artériopathies obliterantes chroniques des membres inferieurs au

stade III de la classification de Fontaine. Journal malade vasculare, 1989, 14:177–

182.

25. Blume J et al. Placebokontrollierte Doppelblindstudie zur Wirksamkeit von Ginkgo

biloba-Spezialextrakt EGb 761 bei austrainierten Patienten mit Claudicatio

intermittens. VASA, 1996, 2:1–11.

26. Schneider B. Ginkgo biloba Extrakt bei peripheren arteriellen Verschlußkrankheiten.

Arzneimittel-Forschung, 1992, 42:428–436.

27. Haguenauer JP et al. Traitement des troubles de l'equilibre par l'extrait de Ginkgo

biloba. Presse medicale, 1986, 15:1569–1572.

28. Coeur et circulation, 02.97.0 Troubles de l'artériosclérose. IKS monthly bulletin, 1994, 6:532–533.

29. Kade F, Miller W. Dose-dependent effects of Ginkgo biloba extraction on cerebral,

mental and physical efficiency: a placebo controlled double blind study. British

journal of clinical research, 1993, 4:97–103.

30. Auguet M, DeFeudis FV, Clostre F. Effects of Ginkgo biloba on arterial smooth muscle responses to vasoactive stimuli. General pharmacology, 1982, 13:169–171, 225–230.

31. Auguet M, Clostre F. Effects of an extract of Ginkgo biloba and diverse substances on the phasic and tonic components of the contraction of an isolated rabbit aorta.

General pharmacology, 1983, 14:277–280.

32. Peter H, Fisel J, Weisser W. Zur Pharmakologie der Wirkstoffe aus Ginkgo biloba.

Arzneimittel-Forschung, 1966, 16:719–725.

33. Pincemail J et al. In: Farkas L, Gabor M, Kallay F, eds. Flavonoids and bioflavonoids.

Szeged, Hungary, 1985:423.

34. Barth SA et al. Influences of Ginkgo biloba on cyclosporin induced lipid peroxidation

in human liver microsomes in comparison to vitamin E, glutathione and N-acetylcysteine.

Biochemical pharmacology, 1991, 41:1521–1526.

35. Pincemail J et al. Ginkgo biloba extract inhibits oxygen species production generated

by phorbol myristate acetate stimulated human leukocytes. Experientia, 1987, 43:181–184.

36. Pincemail J, Dupuis M, Nasr C. Superoxide anion scavenging effect and

superoxide dismutase activity of Ginkgo biloba extract. Experientia, 1989, 45:708–712.

37. Robak J, Gryglewski RJ. Flavonoids are scavengers of superoxide anions. Biochemical pharmacology, 1988, 37:837–841.

38. Oberpichler H et al. Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. Pharmacological research communications, 1988, 20:349–352.

39. Krieglstein J. Neuroprotective effects of Ginkgo biloba constituents. European journal of pharmaceutical sciences, 1995, 3:39–48.

40. Braquet P. The ginkgolides: potent platelet-activating factor antagonists isolated

from Ginkgo biloba L.: chemistry, pharmacology and clinical application. Drugs of the

future, 1987, 12:643–648.

41. Oberpichler H. PAF-antagonist ginkgolide B reduces postischemic neuronal damage

in rat brain hippocampus. Journal of cerebral blood flow and metabolism, 1990, 10:133–135.

42. Prehn JHM, Krieglstein J. Platelet-activating factor antagonists reduce excitotoxic

damage in cultured neurons from embryonic chick telencephalon and protect the rat

hippocampus and neocortex from ischemic injury in vivo. Journal of neuroscience

research, 1993, 34:179–188.

43. Larssen RG, Dupeyron JP, Boulu RG. Modčles d'ischémie cérébrale expérimentale

par microsphčres chez le rat. Étude de l'effet de deux extraits de Ginkgo biloba et du

naftidrofuryl. Thérapie, 1978, 33:651–660.

44. Rapin JR, Le Poncin-Lafitte M. Consommation cérébrale du glucose. Effet de l'extrait

de Ginkgo biloba. Presse medica, 1986, 15:1494–1497.

45. Le Poncin-Lafitte MC, Rapin J, Rapin JR. Effects of Ginkgo biloba on changes induced

by quantitative cerebral microembolization in rats. Archives of international

pharmacodynamics, 1980, 243:236–244.

46. Cahn J. Effects of Ginkgo biloba extract (GBE) on the acute phase of cerebral

ischaemia due to embolisms. In: Agnoli A et al., eds. Effects of Ginkgo biloba extract on

organic cerebral impairment. London, John Libbey, 1985:43–49.

47. Chatterjee SS. Effects of Ginkgo biloba extract on cerebral metabolic processes. In:

Agnoli A et al., eds. Effects of Ginkgo biloba extract on organic cerebral impairment.

London, John Libby, 1985:5–14.

48. Karcher L, Zagermann P, Krieglstein J. Effect of an extract of Ginkgo biloba on rat

brain energy metabolism in hypoxia. Naunyn-Schmiedeberg's archives of pharmacology,

1984, 327:31–35.

49. Le Poncin-Lafitte M et al. Ischémie cérébrale aprčs ligature non simultanče des

artčres carotides chez le rat: effet de l'extrait de Ginkgo biloba. Semaine hopitale Paris,

1982, 58:403–406.

50. Iliff LD, Auer LM. The effect of intravenous infusion of Tebonin (Ginkgo biloba) on

pial arteries in cats. Journal of neurosurgical science, 1982, 27:227–231.

51. Duverger D. Anoxie hypobare chez la souris avec les différents extraits de Ginkgo

biloba. Le Plessis Robinson, France, Institut Henri-Beaufour, 1989 (Report no. 1116/89/DD/HK).

52. Duverger D. Anoxie hypobare chez la souris avec l'un des constituants de l'EGB:le

HE 134. Le Plessis Robinson, France, Institut Henri-Beaufour, 1990 (Report no. 1182/90/DD/HK).

53. Krieglstein J, Beck T, Seibert A. Influence of an extract of Ginkgo biloba on cerebral

blood flow and metabolism. Life sciences, 1986, 39:2327–2334.

54. Beck T et al. Comparative study on the effects of two extract fractions of Ginkgo

biloba on local cerebral blood flow and on brain energy metabolism in the rat under

hypoxia. In: Krieglstein J, ed. Pharmacology of cerebral ischemia. Amsterdam, Elsevier,

1986:345–350.

55. Krieglstein J, Oberpichler H. Ginkgo biloba und Hirnleistungsstörungen.

Pharmazeutische Zeitung, 1989, 13:2279–2289.

56. Oberpichler H et al. Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. Pharmacology research communications, 1988, 20:349–352.

57. Lamor Y et al. Effects of ginkgolide B and Ginkgo biloba extract on local cerebral

glucose utilization in the awake adult rat. Drug development research, 1991, 23:219–225.

58. Chatterjee SS, Gabard B. Effect of an extract of Ginkgo biloba on experimental

neurotoxicity. Archives of pharmacology, 1984, 325(Suppl.), Abstr. 327.

59. Otani M et al. Effect of an extract of Ginkgo biloba on triethyltin-induced cerebral

oedema. Acta neuropathology, 1986, 69:54–65.

60. Borzeix MG. Effects of Ginkgo biloba extract on two types of cerebral oedema. In:

Agnoli A et al., eds. Effects of Ginkgo biloba extract on organic cerebral impairment.

London, John Libbey, 1985:51–56.

61. Chatterjee SS, Gabard BL, Jaggy HEW. Pharmaceutical compositions containing

bilobalide for the treatment of neuropathies. US Patent no. 4,571,407 (Feb 18, 1986).

62. Sancesario G, Kreutzberg GW. Stimulation of astrocytes affects cytotoxic brain

oedema. Acta neuropathology, 1986, 72:3–14.

63. DeFeudis FV et al. Some in vitro and in vivo actions of an extract of Ginkgo biloba (GBE 761). In: Agnoli A et al., eds. Effects of Ginkgo biloba extract on organic cerebral impair-ment. London, John Libbey, 1985:17–29.

64. Winter E. Effects of an extract of Ginkgo biloba on learning and memory in mice.

Pharmacology, biochemistry and behavior, 1991, 38:109–114.

65. Stange VG et al. Adaptationsverhalten peripherer und zentraler akustischer

Reizantworten des Meerschweinchens unter dem Einfluss verschiedener Fraktionen

eines Extraktes aus Ginkgo biloba. Arzneimittel-Forschung, 1976, 26:367–374.

66. Raymond J. Effets de l'extrait de Ginkgo biloba sur la préservation morphologique des épithéliums sensoriels vestibulaires chez la souris. Presse médicale, 1986, 15:1484–1487.

67. Denise P, Bustany P. The effect of Ginkgo biloba (EGb 761) on central compensation of a total unilateral peripheral vestibular deficit in the rat. In: Lacour M et al., eds. Vestibular compensation: facts, theories and clinical perspectives. Paris, Elsevier, 1989:201–208.

68. Lacour M, Ez-Zaher L, Raymond J. Plasticity mechanisms in vestibular compensa-tion in the cat are improved by an extract of Ginkgo biloba (EGb 761). Pharmacology,

biochemistry and behavior, 1991, 40:367–379.

69. Vargaftig BB et al. Platelet-activating factor induces a platelet-dependent

bronchoconstriction unrelated to the formation of prostaglandin derivatives.

European journal of pharmacology, 1982, 65:185–192.

70. Vargaftig BB, Benveniste J. Platelet-activating factor today. Trends in pharmacological sciences, 1983, 4:341–343.

71. Desquand S et al. Interference of BN 52021 (ginkgolide B) with the broncho-pulmonary effects of PAF-acether in the guinea-pig. European journal of pharmacology, 1986, 127:83–95.

72. Desquand S, Vargaftig BB. Interference of the PAF-acether antagonist BN 52021 in

bronchopulmonary anaphylaxis. Can a case be made for a role for PAF-acether in

bronchopulmonary anaphylaxis in the guinea-pig? In: Braquet P, ed. Ginkgolides, Vol.

1. Barcelona, JR Prous, 1988:271–281.

73. Braquet P et al. Involvement of platelet activating factor in respiratory anaphylaxis,

demonstrated by PAF-acether inhibitor BN 52021. Lancet, 1985, i:1501.

74. Költringer P et al. Die Mikrozirkulation und Viskoelastizität des Vollblutes unter

Ginkgo biloba extrakt. Eine plazebokontrollierte, randomisierte Doppelblind-Studie.

Perfusion, 1989, 1:28–30.

75. Költringer P et al. Mikrozirkulation unter parenteraler Ginkgo biloba Extrakt-Therapie.

Wiener Medizinische Wochenschrift, 1989, 101:198–200.

76. Jung F et al. Effect of Ginkgo biloba on fluidity of blood and peripheral microcircula-tion in volunteers. Arzneimittel-Forschung, 1990, 40:589–593.

77. Schaffler K, Reeh PW. Doppelblindstudie zur hypoxieprotektiven Wirkung eines

standardisierten Ginkgo-biloba-Präparates nach Mehrfachverabreichung an gesunden

Probanden. Arzneimittel-Forschung, 1985, 35:1283–1286.

78. Hofferberth B. Simultanerfassung elektrophysiologischer, psychometrischer und

rheologischer Parameter bei Patienten mit hirnorganischem Psychosyndrom und

erhöhtem Gefässrisiko—Eine Placebo-kontrollierte Doppelblindstudie mit Ginkgo

biloba-Extrakt EGB 761. In: Stodtmeister R, Pillunat LE, eds. Mikrozirkulation in Gehirn

und Sinnesorganen. Stuttgart, Ferdinand Enke, 1991:64–74.

79. Witte S. Therapeutical aspects of Ginkgo biloba flavone glucosides in the context of

increased blood viscosity. Clinical hemorheology, 1989, 9:323–326.

80. Artmann GM, Schikarski C. Ginkgo biloba extract (EGb 761) protects red blood cells

from oxidative damage. Clinical hemorheology, 1993, 13:529–539.

81. Ernst E, Marshall M. Der Effekt von Ginkgo-biloba-Spezialextrakt EGb 761 auf die

Leukozytenfilterabilität—Eine Pilotstudie. Perfusion, 1992, 8:241–244.

82. Rudofsky G. Wirkung von Ginkgo-biloba-extrakt bei arterieller Verschlusskrankheit.

Fortschritte der Medizin, 1987, 105:397–400.

83. Lagrue G, et al. Oedčmes cycliques idiopathiques. Rôle de l'hyperperméabilité

capillaire et correction par l'extrait de Ginkgo biloba. Presse médicale, 1986, 15:1550–1553.

84. Gerhardt G, Rogalla K, Jaeger J. Medikamentöse Therapie von Hirnleistungsstö-rungen. Randomisierte Vergleichsstudie mit Dihydroergotoxin und Ginkgo biloba-Extrakt.

Fortschritte der Medizin, 1990, 108:384–388.

85. Hopfenmüller W. Nachweis der therapeutischen Wirksamkeit eines Ginkgo biloba

Spezialextraktes. Arzneimittel-Forschung, 1994, 44:1005–1013.

86. Meyer B. Etude multicentrique randomisée a double insu face au placebo du

traitement des acouphčnes par l'extrait de Ginkgo biloba. Presse medicale, 1986, 15:1562–1564.

87. Sprenger FH. Gute Therapieergebnisse mit Ginkgo biloba. Ärztliche Praxis, 1986, 12:938–940.

88. Witt U. Low power laser und Ginkgo-Extrakte als Kombinationstherapie. Hamburg,

Germany (unpublished document; available through NAPRALERT, see reference 5).

89. Coles RRA. Trial of an extract of Ginkgo biloba (EGB) for tinnitus and hearing loss.

Clinical otolaryngology, 1988, 13:501–504.

90. Fucci JM et al. Effects of Ginkgo biloba extract on tinnitus: a double blind study. St.

Petersberg, FL, Association for Research in Otolaryngology, 1991.

91. Holgers KM, Axelson A, Pringle I. Ginkgo biloba extract for the treatment of tinnitus.

Audiology, 1994, 33:85–92.

_____

Annex

Participants in the WHO Consultation on Selected

Medicinal Plants

Munich, Germany, 8–10 July 1996

Dr Keita Arouna, National Institute for Research in Public Health, Bamako, Mali

Professor Elaine Elisabetsky, Department of Pharmacology, Federal University of Rio

Grande do Sul, Porto Alegre, Brazil

Professor Norman Farnsworth, University of Illinois at Chicago, College of Pharmacy,

Chicago, IL, USA

Professor Harry Fong, University of Illinois at Chicago, College of Pharmacy, Chicago, IL, USA

Dr Abdel-Azim M. Habib, Professor of Pharmacognosy, Faculty of Pharmacy, University

of Alexandria, Alexandria, Egypt

Dr Djoko Hargono, Former Head, Directorate General of Drugs and Food Control,

Ministry of Health, Jakarta, Indonesia

Dr Konstantin Keller, Director, Federal Institute of Drug and Medicinal Products, Berlin,

Germany

Professor Fritz H. Kemper, Umweltprobenbanken für Human-Organproben, University

of Münster, Münster, Germany

Mr Eftychios Kkolos, Director, Pharmaceutical Services, Ministry of Health, Nicosia, Cyprus

Dr Mamadou Koumaré, School of Medicine and Pharmacy, Bamako, Mali

Dr Gail Mahady, University of Illinois at Chicago, College of Pharmacy, Chicago, IL, USA

Dr Satish Mallya, Representative, Bureau of Pharmaceutical Assessment, Health Protection Branch, Drugs Directorate, Ottawa, Ontario, Canada

Professor Tamas Paal, National Institute of Pharmacy, Budapest, Hungary

Dr Tharnkamol Reancharoen, Food and Drug Administration, Ministry of Public Health,

Bangkok, Thailand

Dr Gillian Scott, National Botanical Institute, Conservation Biology Research Unit, Cape

Town, South Africa

Dr Geoffrey N. Vaughan, National Manager, Therapeutic Goods Administration, Com- monwealth Department of Health, Housing and Community Service, Woden, Australian Capital Territory, Australia

Mr Tuley De Silva, Special Technical Adviser, United Nations Industrial Development

Organization, Vienna, Austria

WHO Secretariat

Dr Mary Couper, Medical Officer, Division of Drug Management and Policies, World

Health Organization, Geneva, Switzerland

Dr Martijn ten Ham, Chief, Drug Safety, Division of Drug Management and Policies,

World Health Organization, Geneva, Switzerland

Dr Jutta Schill, Technical Officer, Traditional Medicine Programme, Action Programme

on Essential Drugs, World Health Organization, Geneva, Switzerland

Dr Xiaorui Zhang, Medical Officer, Traditional Medicine Programme, Action

Programme on Essential Drugs, World Health Organization, Geneva, Switzerland.

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