Studie über die Einnahme von Weidenrinden-Extrakt, Salicin und Salicortin sowie Synthesen von Salicylsäure-Glycosiden und Salicin-Analoga

Die Anwendung der Weidenrinde als Analgetikum und Antipyretikum geht zurück bis in die Antike. Mit dem Aufleben der modernen Phytotherapie rückte sie wieder in den Fokus wissenschaftlichen Interesses. Die analgetische und antipyretische Wirkung ist wahrscheinlich auf das Phenolglycosid Salicin zurüc...

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Bibliographic Details
Main Author: Buß, Tanja
Contributors: Imming, Peter (Prof.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2005
Pharmazeutische Chemie
Online Access:PDF Full Text
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Table of Contents: The use of willow bark as an analgetic and antipyretic drug dates back to the ancient world. In connection with the revival of phytotherapy, scientific interest for the bark has increased during the past years. The phenolglycoside salicin is probably responsible for the analgetic and antipyretic properties of willow bark. Salicylic acid is known to be the active metabolite of the precursor salicin. We examined the plasma levels of salicylic acid after oral application of an extract from willow bark and of the phenolglycosides salicin and salicortin on four healthy volunteers. There were no differences in maximum plasma levels of salicylic acid and area under the curve after administration of salicin in comparison to an extract from willow bark containing an equal amount of salicin. However, there was a significant difference in the time of invasion of salicylic acid. After application of salicin the maximum plasma level of salicylic acid is already reached after 1 hour. After the application of an extract from willow bark it took 3.5 hours to reach the maxiumum plasma level of salicylic acid. The application of salicortin resulted in a lower plasma level of salicylic acid in comparison to salicin and willow bark. According to literature reports, willow bark has an effect on acute rheumatic fever (ARF). ARF is not to be confused with chronic rheumatic diseases, but is a bacterial infection. We therefore tested for antibacterial effects of saligenin, salicylic acid and gentisinic acid against serveral Streptococcus strains. However, the compounds showed no antibacterial effect. This proves that the beneficial effect of salicylates in ARF is due to their antiphlogistic and analgetic activity. We further synthesised a number of salicylic acid glycosides and analogues of salicin in order to investigate the influence of different sugar moieties on the ease of hydrolysis. This is of importance because the rate-limiting step in salicin absorption is the hydrolysis of the acetal moiety, needing intestinal and bacterial glycosidases of which there are few with varying activity between individual patients. We prepared beta-salicin, its galactose analogue, and alpha-salicin. The hydrolytic stability of alpha- and beta-salicin in artificial gastric and intestinal fluid was investigated. Finally, a synthesis of an arachidonyl salicylic acid ester for further studies on the action of metabolites from non-steroidal anti-inflammatory drugs was developed.