Madaus GmbH

More than 90% of all fatal mushroom poisonings worldwide are due to amatoxin containing species that grow abundantly in Europe, South Asia, and the Indian subcontinent. Many cases have also been reported in North America. Initial symptoms of abdominal cramps, vomiting, and a severe cholera-like diarrhea generally do not manifest until at least six to eight hours following ingestion and can be followed by renal and hepatic failure. Outcomes range from complete recovery to fulminant organ failure and death which can sometimes be averted by liver transplant. There are no controlled clinical studies available due to ethical reasons, but uncontrolled trials and case reports describe successful treatment with intravenous silibinin (Legalon® SIL). In nearly 1,500 documented cases, the overall mortality in patients treated with Legalon® SIL is less than 10% in comparison to more than 20% when using penicillin or a combination of silibinin and penicillin. Silibinin, a proven antioxidative and anti-inflammatory acting flavonolignan isolated from milk thistle extracts, has been shown to interact with specific hepatic transport proteins blocking cellular amatoxin re-uptake and thus interrupting enterohepatic circulation of the toxin. The addition of intravenous silibinin to aggressive intravenous fluid management serves to arrest and allow reversal of the manifestation of fulminant hepatic failure, even in severely poisoned patients. These findings together with the available clinical experience justify the use of silibinin as Legalon® SIL in Amanita poisoning cases.

A fast and accurate densitometric method was developed and validated to quantify Plantaginis ovatae semen (also: 'ispaghula seed') in Agiocur.Ispaghula seeds have a long history of use as a laxative, but still there was no method for the quantification in the medicinal product.Because of the increasing number of guidelines for medicinal products, it was necessary to develop an appropriate method.The selected leading-substance, xylose, in ispaghula seed is the main sugar in the mucilage layer of the seed husks.This mucilage produces the laxative effect by acting mainly mech.The effect starts when the seeds come into contact with water, and the mucilage polysaccharides begin to swell.The anal. method is based on the densitometric evaluation of the TLC-plate after the second development with the mobile phase acetonitrile-water (90:10, volume/volume).The xylose zone occurs at an Rf-value of 0.56.Xylose is completely separated from the other sugars in the hydrolyzate.The derivatisation reagent 4-aminobenzoic acid is used to color xylose to a red-brown color.The evaluation in the TLC-scanner is executed by using the peak height at 366 nm.The recovery from xylose in the finished-product-excipient (placebo) mixture is between 102 and 106 percent.The precision of a six-time preparation of the hydrolyzate from the seeds of a regular batch amounts to a relative standard variation (RSD) of 1.59 percent.As a result, Agiocur contains 140 mg/g xylose delivered by the P. ovatae semen.

A review.For many essential oils imported from outside Europe full GMP requirements can hardly be fulfilled.Therefore they require a specific approach suitable for Atypical Actives.Such a risk-based approach is proposed using the established model of the Failure Mode and Effective Anal. (FMEA).It consists in the quantification of the risk by numbers and its expression by multiplication of the severity by the probability and by the detectability of the occurrence of the failure/risk.A specific template is presented which can be used for a risk assessment of essential oils in order to guarantee their quality and safety.