The Shiunko Project-New Efforts for the Internationalization of Kampo Medicine

~Clinical trial of Shiunko Ointment in Ethiopian patients with localized cutaneous Leishmaniasis.~
This condition has a very mild hereditary photosensitivity which has almost no symptoms other than strong sunburn, but for some 30 years since it was reported, the causative gene was unknown.

Juntra Karbwang, Kenji Hirayama;
Department of Immunogenetics, Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Nagasaki University

Oumer Ali, Abraham Aseffa
Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia

Takashi Okusa
Okusa Pharmaceutical Co., Yokosuka, Kanagawa

[Purpose]

Besides well recognized major global infectious diseases such as malaria, tuberculosis or AIDS, the burden on the entire human race of neglected tropical infectious diseases such as parasitic helminth disease, insect-borne protozoan disease (leishmaniasis, trypanosomiasis) and dengue fever is thought to be equal to or greater than that of cancer or lifestyle related diseases. What these infectious diseases have in common is that the regions where they are prevalent lack sufficient health policies due to problems of poverty. Our institute is conducting technology transfers of research and development and human resource development which contribute to the fight against infectious diseases in these regions. In FY 2011, the Department of Clinical Product Development was launched as a new field, and started clinical development activities to create new products which are needed in the field such as drugs, diagnostics and vaccines, and to deliver them to patients who need them.

[Methods]

At the Institute of Tropical Medicine’s Department of Clinical Product Development, we consider the use of traditional medicines, especially crude drugs, to be crucial as one development strategy for effective drugs to control these tropical infectious diseases. Reasons for this include that if the purpose is to expand the application of Kampo medicines, it is possible to greatly reduce the burden of safety tests which are the most difficult step in development, and once they are approved, it is highly possible that technology can proactively be introduced to the country and products of certain quality produced, even in developing countries with a comparatively weak technology base. Thus it was decided to conduct a clinical research on Shiunko as a treatment for cutaneous leishmaniasis as our first clinical study. WHO has issued a guideline on the clinical development of crude drugs, and this study was conducted in accordance with this guideline, with a protocol based on the international standard GCP (Good Clinical Practice). Regarding the efficacy of Shiunko, a traditional Kampo medicine of Japan, against cutaneous leishmaniasis, clinical trials in patients with New World leishmaniasis in Peru, and those results have already been reported to the Pharmaceutical Society of Japan by Fuchino et al. of the National Institute of Biomedical Innovation.

The first meeting was held at the Armauer Hansen Research Institute (AHRI) in September 2011, and sponsors agreed to conduct a joint clinical trial in the epidemic region of Northern Ethiopia by the director of the institute on the Ethiopian side and the Institute of Tropical Medicine (NEKKEN)’s Department of Immunogenetics on the Japanese side. After visiting the trial site and meeting the head of the regional health center, actual patients or residents were gathered and the intent was explained by a local dermatologist. The place of residence of the patients and the arrangement of the clinic called the health spot were carefully observed, and it was judged that a clinical trial of 4 weeks with 2-month follow-up were possible. It was found that the lard contained in most Shiunko is undesirable for religious reasons.

A meeting was held at the institute on a more detailed treatment plan, the following protocol was prepared, and we applied for ethical review in Ethiopia and Japan.

Implementers	Armauer Hansen Research Institute, Nagasaki University Institute of Tropical Medicine
Trade Name	Shiunko
Test drug	Shiunko
Trade name	Shiunko
Active component	Lithospermum root extract, Angelica extract

Double-blind randomized placebo-controlled efficacy study by twice daily application of Shiunko to the affected area of patients with localized cutaneous leishmaniasis without complications

Clinical study director	Kenji Hirayama
Coordinator	Juntra Karbwang
Principal investigator	Oumer Ali
Trial site	Ankober Health Center

GMP grade test drug and placebo with only sesame oil and beeswax as base without using lard was provided free of charge by Okusa Pharma Co.
The clinical trial was initiated at the site on April 10, 2013 with the approval of the relevant ethics committees in Japan and Ethiopia and the Ethiopian government authorities.
The results of the study can be expected to be known by September at the earliest.

By taking advantage of Kampo medicines and promoting the expansion of more efficient application, we expect to be able to present a model of new drug developmIn implementing this study, we received the warm support and cooperation of Hiroyuki Fuchino, principal researcher of the Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation; Yukihiro Goda, director of Division of Pharmacognosy, Phytochemistry, and Narcotics, the National Institute of Health Sciences; Professor Hiroshi Kato of the Graduate School of Intellectual Property, Nihon University; President Takashi Okusa and the section chief Hideki Shimana of Okusa Pharma Co; Professor Motoyoshi Satake of the Institute of Environmental Science for Human Life, Ochanomizu University; Professor Setsuko Sekita of the Laboratory of Pharmacognosy and Natural Products Chemistry, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University; Professor Kiichiro Tsutani of the Faculty of Pharmaceutical Sciences, the University of Tokyo; and Professor Haruki Yamada of Kitasato Institute for Life Sciences, Kitasato University. Part of this study was conducted with research funding from the Nagasaki University Global COE Program.ent for infectious diseases that are prevalent in developing countries.

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