Short communicationObservational study on the tolerability and safety of film-coated tablets containing ivy extract (Prospan® Cough Tablets) in the treatment of colds accompanied by coughing
Introduction
Hedera helix Linné (L.) or ivy is an evergreen cirrus belonging to the family of Araliaceae. It is the only saponin-containing herbal drug which is considerably used in monotherapy due to expectorant and bronchospasmolytic effects. A number of controlled clinical studies have demonstrated its respective therapeutic effectiveness using a dry extract of ivy leaves for human use prepared from an aqueous-ethanolic extract (extracting medium: ethanol 30%, Drug-Extract Ratio (DER) 5–7.5:1) (Meyer-Wegener et al., 1993, Lässig et al., 1996, Hecker, 1997, Mansfeld et al., 1997, Mansfeld et al., 1998). Thus ivy belongs to a group of particularly well researched phytopharmaceuticals (Schulz and Hänsel, 2004, Stauss-Grabo et al., 2008). Aqueous extraction of its juvenile leaves has been used since the 19th century in traditional medicine for the treatment of respiratory disorders. Today various formulations of medicinal products containing ivy leaves dry extract such as syrup, effervescent tablets, drops, tablets and suppositories are available.
Recently the efficacy of this extract has been reviewed (Guo et al., 2006, Hofmann et al., 2003, Landgrebe et al., 1999). Besides catarrh of the upper respiratory tract, the Commission E monograph “Ivy leaves”, the ESCOP and the HMPC monograph consequently also name the symptomatic treatment of chronic-inflammatory bronchial diseases with the accompanying symptom of cough as therapeutic indications (Kommission, 1988, ESCOP, 2003, EMA, 2009). Based on this well documented and verified clinical and pharmacological efficacy the ‘Study Group History of the Development of Medicinal Botany’ of the University of Würzburg, Germany, selected ivy as the ‘medicinal plant of the year’ 2010, a nomination provided annually in Germany (Czygan et al. 2010).
The tolerance of different ivy extract-containing preparations with exception of the film-coated tablets has likewise been tested many times in various studies (Hecker et al., 2002, Bolbot et al., 2004, Fazio et al., 2006).
For a long time it was assumed, that saponins generally would be absorbed by the gastrointestinal tract only to a very small extent, if at all, and thus no systemic effects were to be expected following oral administration. In the year 2004, α-hederin, a triterpenesaponin from therapeutically used ivy leaf dry extract, was identified as the central molecule responsible for the therapeutic effect (Hegener et al., 2004, Runkel et al., 2005). This was confirmed by recent in vitro studies showing that the mucolytic and expectorant action of ivy is based on indirect β2-adrenergic effects and that this is due to the saponins α-hederin and Hederacoside C, the latter of which is metabolised to α-hederin in the organism (Sieben et al. 2009). Under stimulating conditions α-hederin inhibits the intracellular uptake of β2-receptors and leads to an increased β2-adrenergic response of the cell. The description of α-hederin as the primary effective ingredient at a molecular level offered for the first time a plausible in vitro explanatory model for the pulmonary effects of ivy leaf dry extract observed in numerous clinical trials and therapeutically used in humans.
Section snippets
Study drug
The study was performed with film-coated tablets each containing 25 mg of ivy leaves dry extract (extracting medium: ethanol 30%, DER 5–7.5:1 [Prospan® Cough Tablets]). In order to specify the content of ivy leaves dry extract used for the preparation of the study drug, the saponin Hederacoside C is used as the primary reference substance following the requirements of the European Pharmacopoeia (content of Hederacoside C used for the HPLC-quantitative analysis calculated via HPLC against ivy
Demographic and disease data
A total of 331 patients was included, 330 patients (206 female and 124 male) were evaluable. One female patient was excluded from the evaluation because she admitted not to have taken any dose of the study medication. Deviating from the study plan, an 11-year old girl was included and evaluated as well. Thus, patients included were between 11 and 85 years old (mean/median: 42/43 years). Fig. 1 shows that most of these patients were between 20 and 60 years old. The treatment was mainly initiated
Discussion
This observational study fulfilled the ‘guideline on population exposure’ (CPMP 1995) with a minimum requirement of 301 patients to detect (very) frequent ADRs with an incidence of at least 1%. In this study 330 patients were evaluated after a treatment with film-coated tablets containing ivy leaves dry extract (extracting medium: ethanol 30%, DER 5–7.5:1 [Prospan® Cough Tablets]). 310 of 330 evaluable patients received an at least 7-day treatment.
Both patients (96.4%) and attending
Acknowledgment
The authors thank Karl Ludwig Rost for his help in editing this manuscript.
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2020, Industrial Crops and ProductsCitation Excerpt :Rutin, isoquercitrin, quercetin, apigenin, kaempferol and 6−7-dihydroxy isoflavone were minor compounds that corresponded to the phytogeographical distribution pattern (Table 3). The phenolic fraction due to its antioxidant, antispasmodic and anti-inflammatory properties contribute to the treatment of chronic-inflammatory bronchial diseases (Stauss-Grabo et al., 2011) and the samples containing great fractions of phenolics could be of interest for the preparation of standardized extracts. Amino acids in our tested ivy leaf samples are mainly composed of alanine and proline.