A Valuable Option for the Treatment of Respiratory Diseases: Review on the Clinical Evidence of the Ivy Leaves Dry Extract EA 575®.

Preparations from ivy leaves (Hederae helicis folium, Hedera helix) dry extracts are well established in the treatment of different respiratory diseases. Until today, the efficacy and safety of ivy leaf preparations has been demonstrated in a variety of controlled clinical studies and non-interventional studies. These results were nearly exclusively obtained using the commercial ivy leaves dry extract EA 575®. This paper will provide information on the clinical data obtained with this special extract, showing the importance of those preparations as a valuable therapeutic option for the treatment of acute and chronic respiratory diseases. Overall, 18 publications covering clinical trials and non-interventional studies of, in total, 65 383 patients suffering from acute as well as chronic respiratory diseases were included.

Assessment of genotoxicity of herbal medicinal products: application of the "bracketing and matrixing" concept using the example of Valerianae radix (valerian root).

An assessment of genotoxicity is a precondition for marketing authorization respectively registration of herbal medicinal products (HMPs), as well as for inclusion into the 'Community list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products' established by the European Commission in accordance with Directive 2001/83/EC as amended, and based on proposals from the Committee on Herbal Medicinal Products (HMPC). In the 'Guideline on the assessment of genotoxicity of herbal substances/preparations' (EMEA/HMPC/107079/2007) HMPC has described a stepwise approach for genotoxicity testing, according to which the Ames test is a sufficient base for the assessment of genotoxicity in case of an unequivocally negative result. For reducing efforts for testing of individual herbal substances/preparations, HMPC has also developed the 'guideline on selection of test materials for genotoxicity testing for traditional herbal medicinal products/herbal medicinal products' (EMEA/HMPC/67644/2009) with the aim to allow testing of a standard range of test materials which could be considered representative of the commonly used preparations from a specific herbal drug according to a 'bracketing/matrixing' approach. The purpose of this paper is to provide data on the practical application of this bracketing and matrixing concept using the example of Valerianae radix, with the intention of facilitating its inclusion in the "Community list". Five extraction solvents, representing the extremes of the polarity range and including also mid-range extraction solvents, were used, covering the entire spectrum of phytochemical constituents of Valerianae radix, thereby including polar and non-polar constituents. Extracts were tested in the Ames test according to all relevant guidelines. Results were unequivocally negative for all extracts. A review of the literature showed that this result is in accordance with the available data, thus demonstrating the lack of a genotoxic potential. In conclusion the two guidelines on genotoxicity provide a practically applicable concept. Valerianae radix has no genotoxic potential, supporting its use in HMPs and its inclusion in the Community list.

Traditional use of medicinal agents: a valid source of evidence.

Traditional knowledge uncovered by serious historical research may help to identify new therapeutic agents. It also plays a part in safety evaluation and drug regulation. So far, however, this way of gaining knowledge is very much neglected in the concept of evidence based medicine, which is in no way contradictory to traditional use. Thus, the true meaning of the word 'tradition' is described, while reliable historical sources are quoted. It is then shown how research into the traditional use of medicinal plants is able to reveal knowledge about efficacy and safety of natural products. Several examples successfully leading to new therapeutic options are given. It is then referred to the concept of 'social validation' developed by the Canadian medical historian John Crellin, who also established guidelines for respective research. Eventually, it is proposed to modify the list of evidence levels by inserting an evidence level 4b 'Traditional use in more than one regional cluster'.

Combination of comfrey root extract plus methyl nicotinate in patients with conditions of acute upper or low back pain: a multicentre randomised controlled trial.

This randomised, multicentre, double-blind, three-arm, placebo-controlled trial compared a topical combination of 35% comfrey root extract plus 1.2% methyl nicotinate versus a single preparation of methyl nicotinate or placebo cream for relief of acute upper or low back pain. 379 patients were randomly assigned to three groups (combination, n = 163; methyl nicotinate, n = 164; placebo, n = 52). They applied a 12 cm layer of cream three times daily for 5 days. The primary efficacy variable was the area under the curve (AUC) of the visual analogue scale (VAS) on active standardised movement values at visits 1 to 4. Secondary measures included back pain at rest, pressure algometry, consumption of analgesic medication, functional impairment measured with Oswestry Disability Index, and global assessment of response. The AUC of the VAS on active standardised movement was markedly smaller in the combination treatment group than in the methyl nicotinate and in the placebo group (ANOVA: p < 0.0001). The combination demonstrated superiority to the two other treatment arms, while methyl nicotinate displayed a considerable effect as well.

Comfrey root: from tradition to modern clinical trials.

Comfrey (Symphytum officinale L.) has been used over many centuries as a medicinal plant. In particular, the use of the root has a longstanding tradition. Today, several randomised controlled trials have demonstrated the efficacy and safety. Comfrey root extract has been used for the topical treatment of painful muscle and joint complaints. It is clinically proven to relieve pain, inflammation and swelling of muscles and joints in the case of degenerative arthritis, acute myalgia in the back, sprains, contusions and strains after sports injuries and accidents, also in children aged 3 years and older. This paper provides information on clinical trials, non-interventional studies and further literature published on comfrey root till date.

[Traditional use: phytopharmaceuticals seen from a historical perspective]. / Traditionelle Anwendung: Eine Betrachtung zu pflanzlichen Arzneimitteln aus pharmaziehistorischer Sicht.

In phytopharmacy, the term 'traditional use' is widely found in colloquial language but has also great significance for registration procedures of medicinal products. It is therefore justified to explore its actual meaning from the perspective of social and pharmaceutical history. It is shown that a tradition is founded by transmission of knowledge and techniques over at least three generations, while the life span of a generation may vary widely. Changes and adaptations to technical advancements do not at all avoid but even constitute the development of traditions. Historical research provides valuable knowledge about effectiveness and risk of phytopharmaceuticals. Criteria of traditional use may complement but not substitute modern evidence based methods; however they always need to be applied historically sound.

Comfrey: a clinical overview.

Comfrey has a centuries-old tradition as a medicinal plant. Today, multiple randomized controlled trials have demonstrated the efficacy and safety of comfrey preparations for the topical treatment of pain, inflammation and swelling of muscles and joints in degenerative arthritis, acute myalgia in the back, sprains, contusions and strains after sports injuries and accidents, also in children aged 3 or 4 and over. This paper provides information on clinical trials and non-interventional studies published on comfrey to date and further literature, substantiating the fact that topical comfrey preparations are a valuable therapy option for the treatment of painful muscle and joint complaints.