RSS-Feed abonnieren
DOI: 10.1055/s-2004-832613
© Georg Thieme Verlag KG Stuttgart · New York
Skin Penetration Studies of Arnica Preparations and of their Sesquiterpene Lactones
Publikationsverlauf
Received: May 3, 2004
Accepted: July 26, 2004
Publikationsdatum:
18. Oktober 2004 (online)
Abstract
Alcoholic preparations of Arnica montana are widely used for the topical treatment of various inflammatory diseases. Sesquiterpene lactones (SLs) are mainly responsible for their anti-inflammatory activity. Here we have studied the penetration kinetics of Arnica tinctures prepared from dried Arnica flowers originating from different chemotypes as well as of their respective dominating SLs, helenalin isobutyrate and 11α,13-dihydrohelenalin acetate. Some alcoholic preparations of fresh Arnica flowers and an Arnica fresh plant gel were also included in the study. We used the stripping method with adhesive tape and pig skin as a model and determined the quantity of SLs in the stripped layers of the stratum corneum (SC). Thus, we observed the penetration into and permeation through this uppermost part of the skin. Whereas isolated SLs permeate through the SC only in a very small amount, permeation of SLs was much higher when they were present in the tinctures. Furthermore, differences of permeation were observed between helenalin and dihydrohelenalin derivatives. Permeation through the SC could be determined for the tested Arnica preparations of fresh Arnica flowers with two preparations showing the best penetration behaviour of all the tested substances. Moreover, the effects of incubation time as well as of repeated applications were investigated with one preparation. Altogether, this study shows that a sufficient amount of SLs might permeate the skin barrier by using Arnica preparations to exert anti-inflammatory effects and that the topical use of plant preparations may be advantageous compared to the isolated compounds.
Key words
Arnica montana - Asteraceae - sesquiterpene lactones - skin penetration - herbal medicines
References
- 1 Merfort I. Arnica: new insights on the molecular mode of action of a traditional medicinal plant. Forsch Komplementarmed Klass Naturheilkd. 2003; 10 (Suppl 1) 45-8
- 2 Knuesel O, Weber M, Suter A. Arnica montana gel in osteoarthritis of the knee: an open, multicenter clinical trial. Adv Ther . 2002; 19 209-18
-
3 Merfort I.
Arnica
. In: Hänsel R, Keller K, Rimpler H, Schneider G (eds)
Handbuch der Pharmazeutischen Praxis . Springer-Verlag, Berlin, Heidelberg, New York 1990: pp 342-57 - 4 Peschka R. Herstellung und Entwicklung liposomenhaltiger Zubereitungen mit hydrophilen Arzneistoffen zur topischen Anwendung. Thesis, University Tübingen 1994
- 5 Lindemann U, Weigmann H J, Schaefer H, Sterry W, Lademann J. Evaluation of the pseudo-absorption method to quantify human stratum corneum removed by tape stripping using protein absorption. Skin Pharmacol Appl Skin Physiol. 2003; 16 228-36
- 6 Shah V P, Flynn G L, Yacobi A, Maibach H I, Bon C, Fleischer N M. et al . Bioequivalence of topical dermatological dosage forms - methods of evaluation of bioequivalence. AAPS/FDA Workshop on ‘Bioequivalence of Topical Dermatological Dosage Forms - Methods of Evaluating Bioequivalence’. September 4 - 6, 1996, Bethesda, Md. Skin Pharmacol Appl Skin Physiol. 1998; 11 117-24
- 7 Schaefer H, Stuettgen G, Zesch A, Schalla W, Gazith J. Quantitative determination of percutaneous absorption of radiolabelled drugs in vitro and in vivo by human skin. Curr Problems Dermatol. 1978; 7 80-94
- 8 Nicolaides N, Fu H C, Rice G R. The skin surface lipids of man compared with those of eighteen species of animals. J Invest Dermatol. 1968; 51 83-9
- 9 Schmook F P, Meingassner J G, Billich A. Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int J Pharm. 2001; 215 51-6
- 10 Willuhn G, Leven W. On the qualitative and quantitative analysis of the sesquiterpene lactones of Arnicae flos DAB 9. Pharm Ztg Wiss. 1991; 136 32-9
- 11 Kalia Y N, Alberti I, Sekkat N, Curdy C, Naik A, Guy R H. Normalization of stratum corneum barrier function and transepidermal water loss in vivo . Pharm Res. 2000; 17 1148-50
- 12 Anderson R L, Cassidy J M. Variation in physical dimensions and chemical composition of human stratum corneum. J Invest Dermatol. 1973; 61 30-2
- 13 U S. Department of Health and Human Services, Food and Drug Administration. Guidance for Industry. Bioanalytical Method Validation. http://www.fda.gov/cder/guidance/index.htm 2001
- 14 Kanikkannan N, Kandimalla K, Lamba S S, and Singh M. Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery. Curr Med Chem. 2000; 7 593-608
- 15 Williams A C, Barry B W. Skin absorption enhancers. Crit Rev Ther Drug Carrier Syst. 1992; 9 305-53
- 16 Almirall M, Montana J, Escribano E, Obach R, Berrozpe J D. Effect of D-limonene, alpha-pinene and cineole on in vitro transdermal human skin penetration of chlorpromazine and haloperidol. Arzneimittel-Forsch. 1996; 46 676-80
- 17 Moghimi H R, Williams A C, Barry B W. Enhancement by terpenes of 5-fluorouracil permeation through the stratum corneum: model solvent approach. J Pharm Pharmacol. 1998; 50 955-64
- 18 El Kattan A F, Asbill C S, Kim N, Michniak B B. The effects of terpene enhancers on the percutaneous permeation of drugs with different lipophilicities. Int J Pharm. 2001; 215 229-40
- 19 Gao S, Singh J. In vitro percutaneous absorption enhancement of a lipophilic drug tamoxifen by terpenes. J Control Release. 1998; 51 193-9
- 20 Wagner S, Kratz F, Merfort I. In vitro behaviour of sesquiterpene lactones and sesquiterpene lactone containing plant preparations in human blood, plasma and human serum albumin solutions. Planta Med. 2004; 70 227-33
Prof. Dr. I. Merfort
Institut für Pharmazeutische Wissenschaften
Lehrstuhl für Pharmazeutische Biologie
Universität Freiburg
Stefan-Meier-Str. 19
79104 Freiburg
Germany
Telefon: +49-761-203-8373
Fax: +49-761-203-8383
eMail: irmgard.merfort@pharmazie.uni-freiburg.de