After the long isolation in the Edo era, the new Meiji government tried to import science and culture from western countries. In the field of medical science, Kanpo, Chinese medicine, was abolished and western medicine was introduced in Japan. A medical system was established in 1874, but the division of prescribing medicines and dispensing them had not been introduced yet, and this situation prevented the increase in newborn pharmacists and solid pharmaceutical education for a long time. However, when the division of prescribing and dispensing medicines started in the late 1980s, the demand for pharmacists increased and a six-year pharmaceutical education system was introduced in 2006. The core curriculum that was established about 10 years ago had many problems, but the system was revised in 2013. The goal of the efforts is to improve the situation regarding the quality, quantity and contents of clinical pharmaceutical education for the new generation of pharmacists to come over the next 10 years. It is important to look at the pharmaceutical education of Japan in light of that of France, where the division of prescribing and dispensing medicine, and the pharmacy itself had been established in medieval times, focusing on the history of the educational system and requirements for pharmacists.
The Ministry of Health and Welfare (MHW) (renamed the Ministry of Health, Labour and Welfare [MHLW] in Jan. 2001) amended the Pharmaceutical Affairs Law, resulting in a fundamental reform of the review system for New Drug Applications, based on the 1996 report of the ad-hoc Committee for Drug Safety Ensuring Measures. One of the most important changes in the review system was the establishment of the Pharmaceuticals and Medical Devices Evaluation Center (PMDEC) on July 1, 1997 followed by the Pharmaceuticals and Medical Devices Agency (PMDA) in 2004. In five years, the drug approval system in Japan underwent a series of significant reforms, such as adopting new GCP based on the ICH/E6 (R1), changes relating to ethnic factors in the acceptability of foreign clinical data (ICH/E5 (R1)), and the establishment of a Common Technical Document (CTD) (ICH/M4). The addition of the PMDEC has greatly improved the speed of review for new drugs, especially oncology drugs and orphan drugs. We discuss the philosophy of PMDA in relation to the concept of regulatory science.
In this paper, the writers reviewed in detail the pharmaceutical market and the shifts in manufacturing and sales including the trade balance in Japan over a thirty-year period from 1980 to 2010. From the 1980s to the 1990s, many innovative pharmaceutical products were developed and launched in the Japanese market. During the same period, some Japanese companies managed to develop their first internationally marketable drugs, which were antibiotics and effective remedies for the digestive and circulatory organs. During this period, Japanese pharmaceutical companies were also able to launch some of blockbuster drugs. For two decades, the pharmaceutical market grew rapidly. For this reason, it can be called "The Growth Period for Pharmaceutical Products" in Japan. After that period, drug development and sales slowed down due to a lack of expertise in genetic engineering and biotechnologies. This situation caused a large deficit in the trade balance for Japanese pharmaceutical products. However, with regard to the trade balance (including technical royalties) for pharmaceutical product technologies, Japan remains in the black even today.
Scurvy, a vitamin C deficiency, was rampant during the age of discovery in Europe. In the mid-17th century, “Pasqua Rosée,” the first coffee house in London, put an ad in the newspaper “Publick Adviser” clearly stating, “It (coffee) is excellent to prevent and cure dropsy, gout, and scurvy.” A Netherlands trade merchant carried the information to Nagasaki, Japan, along with coffee beans harvested in the Netherlands’ new territory, Java Island. A Japanese physician in Nagasaki, Dr. Kai Hirokawa, translated the information into Japanese in his new book, “Dutch Medicines,” published in 1803. According to the ancient documents stored in Wakkanai City, Japan, the coffee beans were distributed to Tsugaru Clan soldiers who were guarding the northern coastline from 1855 to 1856. The purpose of the distribution was the prevention of scurvy and dropsy. As the result, none of the soldiers died from scurvy during the winter of 1855-1856. This paper discusses the pharmacological relationship between coffee micronutrients and vitamin deficiency syndrome.
Summary Early Meiji Japan witnessed a boom in Japanese Ginseng exports, but the years between 1880 and 1886 brought a sharp decline. Previous research linked this recession to chaos in domestic production and by illegal imports of Korean Ginseng without presenting data about the actural fluctuation of Ginseng output. Moreover, as the biggest target market of Japanese Ginseng exportation, the situation in Qing, China should be included in any analysis. Based on statistical data collected in China and Japan, this study clarifies the reasons for the sharp decline during the early 1880s.
In China, present-day, the tree peony is not only being used in traditional medicine, but has also been extolled to a status equivalent to that of a national flower. This plant is now called mudan in the Chinese language, although it seems disputable what plant mudan originally referred to. Particularly, the botanical accounts on mudan in the Newly Revised Canon of Materia Medica (Xinxiu Bencao) contain some discrepancies regarding the actual features of the tree peony. The primary investigation of this issue has already been published, and reached the conclusion that mudan used to refer to Ardisia spp. However, further verifications looking at different aspects are required. This paper intends to show that mudan and Ardisia ssp. have shared drug properties and usages as listed in various Chinese medical texts. These consistencies certify that mudan can possibly be replaced with Ardisia ssp., when we utilize the pre-Tang dynasty's prescriptions. In addition, there is further significant evidence for the notion that mudan used to refer to Ardisia ssp.
Cinchona is known as a magic bullet for malaria and its cultivation was dominated by Java on a global scale in the 19th century. In 1875, in accordance with a suggestion by Takeaki Enomoto, the Meiji government made a request to the Dutch government that cinchona seedlings be distributed to Japan. In response to that request, in 1876, 42 cinchona seedlings arrived in Yokohama from Java. It was the first time cinchona seedlings were shipped to Japan. After that, cinchona seeds and seedlings were shipped to Japan a total of three times between 1876 and 1883. The seeds shipped in 1878 were raised at the Nishigahara Agricultural Experiment Station and then planted at nine places in both Okinawa and Kagoshima Prefectures in 1882. The planter was Yasusada Tashiro. However, all of the planted seedlings had died by 1884. The first national farming plan of cinchona in Japan ended in failure. These matters were found in documents included in Nomutenmatsu compiled by the Ministry of Agriculture and Commerce of the Meiji government in 1888.
INUBUSHI SEIYAKU, a Japanese pharmaceutical company established in 1807, manufactures KEISHIN-TAN. This is an original drug developed by the company, and consists of 14 exotic natural medicines, spikenard, oriental bezoar, musk, agarwood, etc. It has been used for adjusting the autonomic nervous system and physical conditions. We studied the original methods of the traditional quality management techniques handed down within INUBUSHI SEIYAKU in selecting the appropriate spikenard (Nardostachys chinensis) for medicinal use. Currently, spikenards are mainly used as incense rather than medicine. KEISHIN-TAN is a rare case in that the bulk powder of the spikenards is used for pharmaceutical products in Japan. We examined the morphological characteristics and made an analysis of the component of spikenards selected by traditional methods. The raw material of the spikenards was purchased from the Japanese market, and was classified into two categories-superior, fit for medicinal use and defective, to be discarded-by traditional methods of INUBUSHI SEIYAKU. The methods of the characterization of the spikenard by INUBUSHI SEIYAKU were investigated. As a result, only thick spikenard roots over 2.0 cm in length and approximately 0.5 cm in diameter were found to be used, and the total weight of the superior was only 15% of the raw material. By comparing the weights of hexane extracts and GC-MS analyses, the content of calarene--main sedative compound in spikenards--in the superior material was 2.8 times higher than the raw material and 4.3 times higher than the defective material. The ways to devise how to enhance the pharmacological effects of spikenards may be contained in this method. These results revealed the traditional spikenard selection criteria, and may show the indications of using spikenard or its compounds for medicinal purposes.
Valerian has been used as a name for Japanese Valerian and European Valerian root. Valerian in the German market today was originally called Baldrian. Transitions in the standards and the test methods of Valerian root listed in the DAB were studied this time. Moreover, we compared these standards and test methods with those in the USP, BP, EP and JP. We also considered the pharmacology evaluation in Germany. At the time, the standards and test methods had content in accordance with the EP from DAB9 (1986) of the West Germany publication. It also agreed with the EP and BP of the same period. To date in the DAB, botanical features have been mainly derived from the discriminating characteristics of the Valerian root. In DAB9 (1986), standards and test methods were added to the content, enhancing it and making it more stringent. This is thought to have happened as a result of a new, academic finding showing an improvement in the pharmacology level. Valerian root has been listed continuously in the DAB. These listings suggest that Valerian root has continally been evaluated as a sedative. We think that the listing was connected with a relisting in the BP as a result of scientific communications between Britain and Germany, EC member nations, such as through EP publications. On the other hand, the oil made with Japanese Valerian was listed in a radical field in DAB6 (1926) in the past. This is a valuable result, proving that it was used and evaluated as an important herbal medicine from Japan and foreign countries at that time. The Japanese Valerian referred to is not grown in Japan today. Moreover, it is not possible that cultivation will be restarted through good quality revaluation. However, this fact introduces a valuable piece of history supporting the survival of Japanese Valerian and European Valerian root as a sedative in the future.
Blood components and plasma derivatives are two of the most useful tools in modern medicine. When the Portuguese opened the maritime routes to the Far East in the 16th century. Western medicine traveled to Japan on the trading vessels that carried physicians and barber-surgeons to care for the body and Christian missionaries to care for the soul. Skilled interpreters such as Kōgyū Yoshio translated and studied Dutch editions of early medical books, like Lorenz Heister's "Chirurgie" (Nürnberg, 1719), that illustrate the concept of transfusion. The oldest description of transfusion originating in Japan is a handwritten manuscript entitled "Bansui Sensi Chojutsu Shomoku" by Masamichi Nishijima, a student of Bansui Otsuki. It is a list of Otsuki's translated works. He described book names and chapter names in the manuscript, and when he finished translation of a chapter, he marked a circle on the chapter name. The transfusion chapter had a circle. That dates the earliest writing on transfusion in Japanese to 1804, shortly after the death of Kōgyū. Unfortunately, the manuscript translation no longer exists. In 1814, Shunzō Yoshio, grandson of Kōgyū, and in 1820, Tokki Koshimura, translated the figure legends of "Chirurgie." Soon afterwards, after the first report of transfusion from human-to-human by James Blundell in London in 1818, Western medical books published on the subject began to arrive. The works of Christoph Wilhelm Hufeland, Georg Friedrich Most and Carl Canstatt all mentioning transfusion, albeit without details, were translated by Kōan Ogata and Shinryō Tsuboi. During the Edo period, Japan was a closed country; only open to the Dutch through a tiny island in Nagasaki. But Japanese doctors in the Edo period learned about blood transfusion through Dutch-translated versions of Western medical Books. Transfusion began being practiced in Japan in 1919, almost exactly 100 years after the concept was introduced
Domestic production of penicillin was initiated in 1946 and that of streptomycin in 1950. In the early days, however, the quality of products was considerably lower and the capacity of production small. Surprisingly, there was a sufficient amount of penicillin preparations, with a purity of 85% or more, satisfying domestic demand within three years (1949). In the case of streptomycin, within three years (1953), preparations with a purity two-fold higher than initially available were produced in amounts sufficient to meet both domestic demand and create a surplus availability for exporting purposes. Such increases in quality and production were considered to be made possible by strict quality control of penicillin and streptomycin preparations, based on "Minimum Requirements for Penicillin" established in May 1947 and "Minimum Requirements for Streptomycin" established in December 1949. These requirements were also amended over time in order to provide even higher quality standards in response to the evolving improvements in production processes. Life-threatening diseases such as septicemia and pneumonia were controlled by the sufficient supply of high-quality penicillin preparations and the mortality rate of tuberculosis, regarded as a national disease at the time, markedly decreased by that of streptomycin preparations. Achievements of domestic production of penicillin and streptomycin were considered important factors that contributed greatly to the maintenance of public health in Japan.
Ginseng is prepared from Panax ginseng C.A. Meyer root. The root of wild P. ginseng has long tortuous rhizome called traditionally "Rozu" in Japanese. In the present historical studies on ginseng, it has been proven that ginseng has sometimes been used after removing "Rozu" due to its emetic effects. However, ginseng with "Rozu" is prescribed in almost all the present Kampo formulations used clinically in China and Japan. Possible reasons for this are (1) some formulations including "Rozu" have been used for vomiting resulting from the retention of fluid in the intestine and stomach, "tan-in" in Japanese, and (2) the present cultivated ginseng has shorter "Rozu" than wild ginseng. Furthermore, it is proved that "Rozu", rich in ginsenoside Ro with oleanane-type aglycone, is distinguished from ginseng roots rich in ginsenosides Rb1 and Rg1 with dammarane-type aglycone. This is the first report to declare the distribution of ginsenosides in underground parts of wild P. ginseng. Ginsenoside Ro is a minor ginsenoside in ginseng whereas it is the major ginsenoside in P. japonicus rhizome (chikusetsu-ninjin in Japanese). Ginsenoside Ro is characterized by antiinflammatory effects which differ from ginsenosides Rb1 and Rg1 responsible for adaptogenic effects of ginseng. These results suggest that "Rozu" containing both oleanane- and dammarane-type ginsenosides might be a promising raw material distinct from ginseng root or P. japonicus rhizome.
Yagen (see text) is an oriental grinder for crude plant medicines. It consists of a disk and navicular mortar. A Chinese yagen with the inscription, "Product of the Ming-Zhengde Period (See text), (1506-1521 A.D.)" has been housed for 40 years in the Naito Memorial Museum of Pharmaceutical Science and Industry (Kakamigahara, Gifu Prefecture, Japan). To identify the district that produced this yagen, the authors analyzed the elements using an X-ray fluorescence spectrometer. The results showed that the blue design and blue Chinese characters on the yagen were enameled with elements of cobalt, manganese, and iron. Therefore, it is believed that the yagen was made in an old porcelain kiln near Zhangzhou in Fujian Province, China. However, as the period of production could not determined in the present study, further research is needed in the future.
The pharmaceutical industry, which developed through the Meiji and Taisho eras, is apparently one of the most important technological industries. However, only a few papers have been published regarding the entrepreneurships of the industry early on. It is crucial to research this subject in order to explore the process of how highly technical companies progressed in the early stage of modern industrialization in Japan. This paper focuses on two distinguished entrepreneurs, Gisaburo Shiono Jr. and Chobei Takeda the Fifth, who were both from the Dosho district of Osaka City. Gisaburo Shiono Jr. founded Shionogi & Co., Ltd. and Chobei Takeda the Fifth founded Takeda Pharmaceutical Company Limited; both of which are currently outstanding companies in the Japanese pharmaceutical market. The paper reveals that the two entrepreneurs started out by importing chemical materials from western Europe and North America, and then expanded their activities into manufacturing pharmaceutical materials in their own firms. Finally, they succeeded in developing their own new medicine products. Their lifetime histories, surveyed along with management activities, are described to clarify the process of each company's development through a few wartime experiences including World War I. Their achievements were quite similar, but the processes used were different. The case of Gisaburo Shiono Jr. shows his risk management skills, which filled his lack of technological leadership. The case of Chobei Takeda the Fifth shows his ability to gradually adapt the company to change throughout a long history of changing environment.
In 1918, Nippon Fine Chemical Co., Ltd. (NFC) was founded under the name, Nippon Camphor Co., Ltd. for the purpose of unifying the camphor business throughout Japan. The company manufactured purified camphor as a government-monopolized good. Camphor was used as a plasticizer for nitrocellulose, as a moth repellent, as an antimicrobial substance, as a rust inhibitor, and as an active ingredient in medicine. It was also a very important good exported in order to obtain foreign currency. Later on, after World War II and the abolition of the camphor monopoly, the company started manufacturing products related to oils and fats, including higher fatty acids, and expanded its business by developing a new field of chemical industry. In 1971 the company changed its name to Nippon Fine Chemical Co., Ltd., and made a new start as a diversified fine chemicals company. Recently, the fine chemicals division of NFC has concentrated on rather complex molecules, such as active pharmaceutical ingredients, and other chemicals. Since 2000, NFC have started to supply "Presome", precursors of liposome DDS drugs. NFC is strengthening marketing strategies in foreign countries with unique technologies and products.
In Japanese Pharmacopoeia (JPXVII 2016), there is a description about Kanokoso, “This item is the root and rootstock of Kanokoso Valeriana fauriei Briquet (Valerianaceae). Kanokoso Valeriana fauriei Briquet is referring to Ezokanokoso Valeriana fauriei forma yezoensis Hara, which is the same variety. The Hokkai-kisso currently cultivated in Japan is the Ezokanokoso variety. The author analyzed the history of the variety of Japanese Valerian previously cultivated, but it’s incomplete. To maintain the quality and efficacy of a medicine, it is important to disseminate information regarding the origin of the crude drug. To ensure the quality of Kanokoso and stable efficacy of the medicine, it’s indispensable to maintain the original plant variety when cultivated.The author obtained the following knowledge during research. The variety cultivated in Kanagawa early in the Showa era was Japanese Valerian, sometimes being two kinds, lobule and round leaf. It is presumed that the original variety cultivated in Kanagawa early in the Showa era was Hokkai-kisso.The ingredients of the variety of Japanese Valerian cultivated and that which grows wild vary. The basis of the chemical structure of sesqui terpene kinds of α-Kessyl alcohol (KA) and Kessyl glycol diacetate (KGD), etc. has Kessane skeleton. It’s this consistency and is gathered using the same type of system. The consistency is interesting. Pursuing the relation between the consistency and type of system is regarded as a problem. To obtain the same kind of ingredient and form from Hokkai-kisso in the current state seems difficult. To maintain today’s quality of Hokkai-kisso and medicinal efficacy, it’s important for continue to cultivating the plant by dividing the roots for replanting.
Morizo Ishidate was born in the city of Aomori on January 24, 1901, the third son in his family. As the 16th Director General of the NIHS, he announced his decision to reform the organization and implemented this action in 1966. In September 1970, as the president of the Central Pharmaceutical Affairs Council, he decided to stop the use of all quinoform preparations. On May 21, 1973, he held a historic talk with Dr. Taro Takemi. After the meeting, the separation of dispensing and prescribing functions opened a new chapter in pharmaceutical history. Such a heroic and noble life may be due to his faith. In April 1922, he entered “Doushikai,” a dormitory belonging to Tokyo Imperial University. Yoshinosuke Konishi was his best friend in the dormitory. They joined a bible class directed by an American missionary, Miss Laura J. Maukʼ. In September 1947, at the age of 49, Yoshinosuke decided to devote the rest of his life to being an evangelist. After that time, Morizo supported him for 33 years. At the age of 70, Morizo confessed his belief of Jesus Christ’s resurrection from the dead based upon following words in the bible, “Therefore, if anyone is in Christ, he is a new creation. The old has passed away; behold, the new has come,” (2 CORINTHIANS 5 : 17). On July 18, 1996, he passed away at the age of 95.