Development and optimization of a phytotherapeutic preparation based on traditional Japanese Kampo medicine against neuronal disorders

Japanese traditional Kampo medicine is an integral part of the Japanese public health system. Freeze-dried granules of 30% EtOH hot aqueous extracts of 148 Kampo prescriptions are covered by insurance in Japan. One of these is Yokukansan ( Atractylodes lancea rhizome 4.0 g, Poria cocos sclerotium 4.0 g, Cnidium officinale rhizome 3.0 g, Angelica acutiloba root 3.0 g, Bupleurum falcatum root 2.0 g, Glycyrrhiza uralensis root 1.5 g. Uncaria rhynchophylla twigs 3.0 g); used for ADHD, Parkinson, Alzheimer, and other neurodegenerative syndromes. In contrast to the insurance covered contemporary 30% EtOH hot aqueous extract preparations, Yokukansan was traditionally applied as powdered plant drug material mixed with the normal food intake. No critical comparison of the secondary plant constituents ingested via this method versus the industrial extract granules has been reported. Here, a novel galenical for Yokukansan was developed in accordance with the EU directives for Traditional Herbal Medicinal Products (tHMPs). Numerous types of extracts were prepared and phytochemically compared to a traditional-style Kampo decoction, industrial-type 30% EtOH hot aqueous extracts, and a MeOH full extract using TLC and HPLC. Furthermore, a method was developed to reduce the content of simple oligosaccharides in the extract thus lowering the required daily dose for the patient. In contrast to the modern Japanese daily dose of 2.5 g extract granules 3x daily (inacceptable for European patients), we were able to develop a novel dry extract (daily dose 1.5 g) as a basis for more advanced galenicals (e.g. tablets, capsules). Among these a medicinal-syrup (daily dose 10 ml) seemed to be most favourable for the intended use in paediatrics (Attention Deficit Hyperactivity Disorder). Due to the fact that Yokukansan is used in the EU in single prescription since more than 15 years and since centuries in Japan without negative effects, our work opens the possibility to apply for its official registration as a phytopharmacon in Europe.