C.P. Thunberg, a Swedish medical doctor and botanist who arrived in Japan in 1775, is the author of Flora Japonica, which is highly acclaimed for introducing modernized floristics to Japan. As a medical doctor, he reportedly introduced mercury therapy for syphilis to Japan, but the circumstances have been unclear. This paper focuses on Thunberg as a medical doctor as well as Uppsala University School of Medicine,Sweden, where Thunberg learned medicine, and three medical papers he wrote before his trip to Japan in order to demonstrate that he possessed the most advanced medical knowledge of his time. We reviewed Komohijiki written by Kogyu Yoshio, one of the Japanese-Dutch interpreters who learned about mercury water from Thunberg, and books written by van Swieten, an Austrian doctor who clinically evaluated mercury water, and concluded that the mercury water introduced by Thunberg was a 0.1% solution of mercuric chloride, which was later named van Swieten water and included in Western pharmacopoeias from the 1830 s through the 1930 s. In Japan, nearly half a century was needed after the introduction of mercury water before books on Western medicines that introduced correct information were published. The highest dose of mercuric chloride established by van Swieten was retained in the Japanese Pharmacopoeia up to its 5th edition. Thunberg should be regarded highly not only as a botanist but as a medical doctor as well.

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The treasures housed in the Shosoin are said to number over 10,000. They were donated to the great Buddha of Todaiji Temple in 756, after the death of Emperor Shomu．The objects given at that time are noted in a document known as Kokka-Chimpo-Cho and Shuju-yakucho (Memorandum of Medicines) which lists 60 kinds of medicaments. Today, many kinds of medicines can be found in the Shosoin Treasure House. Scientific investigations of the Shosoin medicines were conducted on two occasions. From 1948 to 1952, immediately after World WarII, the first investigation was conducted by a team consisting of Yasuhiko Asahina, as the chief, and 15 other researchers. After this investigation, 38 medicines listed in the Shujuyakucho were found in the Shosoin Treasure House. At that time, chemical studies on the constituents of medicines were not very efficient due to having insufficient knowledge of the chemical principles of traditional drugs, and no techniques or equipment had been developed for chemical analysis. An additional analysis was conducted from 1976 to 1986, at which time some drugs were studied by Shoji Shibata, a member of the first investigation. The results were as follows : Ginseng contains total ginsenosides; licorice contains a high yield of Glycyrrhizin as the sweet agent and some flavonoid glycosides; and rhubarb contain Sennoside A and B, some anthraquinone derivatives and their glycosides. From 1994 to 1995, 50 years after the initial research, a second investigation of the Shosoin medicines was conducted. Shoji Shibata was the chief researcher, and worked with an investigation team consisting of six researchers in total. During this investigation, many kinds of plant glycosides were found in Shosoin medicines. As an interesting fact, four kinds of gelsemium alkaloids were found in Yakatsu ，which is a poisonous drug stored in the Shosoin since 756.

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Shaoyao, the Chinese name of the herbaceous peony, appeared in the Classic of Poetry or Shijing. Shijing　was compiled much earlier than the third century BC when peony was discussed in the botanical treatise by Theophrastus in ancient Greece. However, several Confucian scholars questioned what shaoyao in Shijing actually referred to. In addition, shaoyao was considered to be a fragrant grass and was often added to food as a spice in the Han dynasty, whereas the peony is hardly ever used in that way today. In the three kingdom dynasty, Lu Ji remarked: Since the medicinal shaoyao does not have a particular scent, shaoyao [of Shijing] cannot be identified.”These old descriptions suggest that they may have used a different plant as shaoyao in early China, and accordingly it allows us to reflect on shaoyao in the old Chinese medical texts. This paper traces various hypotheses historically with attention paid to regional differences and ages. The results, confirm that shaoyao has most certainly been a name of the peony since the six dynasties when shaoyao was prized as an ornament plant. Before the six dynasties, four candidates of shaoyao can be listed: the peony itself, water chestnuts (Eleocharis dulcis), magnolia and Szechuan lovage (Ligusticum wallichii), though for all four, sufficient and definitive evidence is lacking.

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The Japanese Orphan Drug Development Support Program was established in 1993. During the 20 years after its establishment, the Ministry of Health, Labour and Welfare (MHLW) has designated 300 medicines and 23 medical devices as orphan. Of these, 192 medicines and 13 medical devices have been approved. Over the last 10 years from April 2003 to March 2013, 97 medicines were approved including 27 medicines for rare diseases, 17 anticancer therapeutic medicines, 13 medicines for HIV/AIDS and 10 medicines to meet multiple medical needs. The appreciable outcomes of these medicines are as follows. Tocilizumab (genetic recombination) is a humanized anti-human interleukin-6 receptor monoclonal antibody of the IGG1 subclass. It was discovered by Osaka University and Chugai Pharmaceutical Co., Ltd., and was approved for improvement of various symptoms associated with Castleman’s disease in 2005. Pirfenidone was approved for idiopathic pulmonary fibrosis in 2008. Mogamulizumab (genetic recombination), a humanized anti-CCR4 monoclonal antibody, was approved for relapsed or refractory CCR4-positive adult T-cell leukemia/lymphoma in 2012. The above three medicines first commenced in Japan. Pegaptanib sodium was approved for subfoveal choroidal neovascularization secondary to age-related muscular degeneration in 2008. Four alum-adjuvanted influenza (H5 N1) prepandemic vaccines were approved for avian influenza pandemic preparedness in 2007, 2010 and 2013. Regarding medical devices, nine medical devices were approved. For example, an implantable ventricular assist device was approved in 2010. It is used to improve the blood circulation until cardiac transplantation is performed in patients who have severe heart failure for which cardiac transplantation is indicated. Since rare diseases are a global issue, working with international partners and sharing information on orphan drugs have been recognized as issues. This includes organizations such as the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA)． The network involving patients and members of the rare diseases community has been improved. For example, the Cancer Philosophy Clinic was set up as a non-profit organization in 2011. Recently, 31 sites have been opened to care for terminally ill cancer patients. Finally, future proposals for the next decade are also outlined.

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Objective : Koan Ogata (K.Ogata : 1810-63), the director of Tekijuku, was a physician who contributed much to the medical profession in the late Edo period resulting from his knowledge of Western medicine. Osaka University inherited various items from his cultural heritage, including a medicine chest with crude drugs stored in six drawers. To make informed decisions regarding suitable preservation strategies, the entire medicine chest, the crude drugs, and the features thereof were noninvasively archived. Methods : Inspection of the medicine chest was performed in accordance with the procedures authorized by the Tekijuku Commemoration Center. We measured the chromaticity, size and weight using a spectrophotometer, digital caliper and electric balance, respectively. Morphological photographs were taken by an art photographer. Detailed structures were observed and recorded using a digital microscope. Results and Discussion : We took approximately 7,000 pictures of the chest itself and its components. There were 70 medicaments stored in the chest, with most of them packed in a paper case with the medicine name written on it. K. Ogata used medicinals (crude drugs) consisting of botanical, animal and mineral origins to treat patients. The second drawer from the top of the chest held 10 pharmaceutical pilltype preparations with different names. In the third to fifth drawers, crude drugs (cut-style : 3.5-46 g) were found in 64 of the 70 cases. Half of the medicinal materials originated from leaves, flowers and seeds, and the others were roots, rhizomes and so on. Several drugs were difficult to identify due to serious damage caused by insects. Some medicine names on the paper cases seemed to suggest European drugs such as salvia, chamomile and cascarilla. The analysis of his chest revealed that he used the most advanced medicines from Europe and China in the Edo period.

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Between 1923 and 2010, there were 119 peptide drugs, including hormonal and interferon drugs, launched in Japan. Of these, insulin is the oldest peptide drug, although in recent years, new insulin drugs have been produced using genetic engineering technology. A special feature in the history of peptide drugs is the development of ACE inhibitors in the 1970s, which triggered the development of a number of new peptide and blockbuster drugs. Since then, other peptide drugs have also been developed using new methods and purification techniques. A typical example is leuprorelin, which was developed using new formulation techniques. In recent years, the development of higher-molecular peptide drugs, especially the development of antibody drugs, has become more popular than that of lower-molecular peptide drugs. The history of antibody drug development will be reported in the next paper.

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Several decades have passed since T. Moore (Liverpool, UK) discovered ubiquinone. The compound having maxium UV absorption at 275nm was isolated from beef heart mitochondria by F.L. Crane (Wisconsin, USA) and named as coenzyme Q (CoQ). Subsequently, the role of CoQ in the mitochondrial electron transport system became apparent. Effects of oral administration of CoQn were carried out initially by K. Folkers (USA) and Y. Yamamura (Japan) and later by many others. Clinical studies revealed some beneficial effects of CoQ on cardiovascular diseases. The present work reports the short history of pharmaceutical development of coenzyme Q and related compounds.

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The word nyu-bachi (mortar) is seen in Shogaku-Kagaku-sho, a book of chemistry in 1874 but its etymon is unknown. The word ru-bo (nyu-bachi in Japanese) is seen in several ancient books in medicine, art and literature, from the 5th to 18th century. In these books, the usage of ru-bo is written as crush the solids. In 1874, the translator Tosen Hoda did not make a new Japanese word for mortar but used the ancient Chinese word ru-bo (nyu-bachi). This was because he found that the usage of European mortar is the same as that of the ancient Chinese ru-bo. The word nyu has several meanings. The etymon of the word nyu-bachi comes from the female breast nyu, not liquid nyu. The reasons are as follows : 1) the usage of ru-bo (nyu-bachi) is for solids, not liquids, and 2) the word bo (bachi) means hemisphere bowl. It may stand for a kind of humor in ancient Chinese male society.

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Jo-zai or tablet is a most popular form of pharmaceutical dosage in modern Japan. The term jo-zai first appears in the Japanese Navy Pharmacopoeia, First Edition (1872). Its Latin name was translated as torikisuki and was written in Japanese katakana characters. Jo-zai translated as trochischi can also be found in the Japanese Pharmacopoeia, First Edition (JP1) (1897)． Its Latin name and definition have changed several times : trochisichi ; pastilli, JP3 (1906) ; tablettae, JP5 (1932) ; tabellae : JP6 (1951), etc． The etymon of the word jo-zai is based on the English word, lozenge. Its square-shaped form is similar to old Japanese silver coins. During Japan's Edo era (1603-1868) and in ancient China, silver coins were called jo. Therefore the word lozenge was translated into Japanese as jo-zai，combining the character for coin with the one for drug, zai.

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The Meiji Restoration was highly significant, and brought a big change for medical and pharmaceutical products. During the Edo period, for a long time, drug production and sales were neglected under the institution of the law. However, the new Meiji government intensified a crackdown on drug production and sales to ensure drug safety and dignity. Furthermore, the government investigated the actual sales conditions of drugs with the aim of a tax on drug sales. Medicine as well as drugs rapidly switched from Chinese medicine into Western medicine. In the Edo period, although drug packaging was wrapped in paper and indicated the brand name, dosage and manufacturer, in the new era, drug packaging had various purposes ; namely, for protection of the contents, convenience of use and to create product individuality.

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