In this paper, as the sequel to Part 3 of the series, the progress of research on organic chemistry in the field of agricultural sciences, in particular agricultural chemistry, is overviewed. The Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA), founded by Umetaro Suzuki in 1924, will soon celebrate its 100th anniversary. The Pesticide Science Society of Japan (PSSJ), founded in 1975, will soon celebrate its 50th anniversary. In the 20th century, JSBBA and PSSJ have actively conducted organic chemical research focusing on natural product chemistry, and have made significant contributions not only to agricultural sciences, but also to medical and pharmaceutical sciences. Here, the authors focus on the field of agrochemicals and touch on the histories of JSBBA and PSSJ. In the process, they mention their predecessors who have contributed to organic chemical research, mainly in the fields of natural product chemistry, bioorganic chemistry, and pesticide chemistry.

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An existing leaflet of the first lead-free powder, Misono Oshiroi, shows that the harmlessness of the white powder was certified by Junichiro Shimoyama and Yoshizumi Tahara. This study investigated the history of this white powder and the background of fabrication of lead-free white powder in Japan. Lead was imported from China to Japan around the middle of 5th century, and from then on, it was used as the material for white powder. Lead poisoning caused by white powder containing lead had become a problem and the Home Ministry issued the Control Law in 1900. Misono Oshiroi is the first lead-free white powder in Japan that was produced when the safety of cosmetics became required. The harmlessness of this product was certified by three pharmacologists. This is the first case of a pharmacist being involved in cosmetic quality certification before the Pharmaceutical Affaires Law was enacted.

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Purpose: Hopfenmehl (Lupulin) has been used as a raw material for beer for many years. On the other hand, in Western Europe, it has been used as a crude drug for a long time as a sedative and a bitter stomachic medicine. From the latter half of the 1800s to the beginning of the 1900s, Hopfenmehl was listed in the pharmacopoeia of various countries, such as Japanese Pharmacopoeia (JP), United States Pharmacopoeia (USP), British Pharmacopoeia (BP), and German Pharmacopoeia (DAB). Approximately 100 years later, just before the 21st century, European Pharmacopoeia (EP) from EP3.0 (1998) to today?s EP10.0 (2020), and BP from BP2000 to today's BP2022, have been continuously listed for about 20 years. Now, in the 21st century, the author investigated the transition of Hopfenmehl standards and test methods listed in EP and BP for 20 years until today, 2022. Then, regarding the standards and tests of the Hopfenmehl components specified in EP and BP, the author considered them while making comparisons with academic information, such as the Hopfenmehl components found in recent academic literature. Furthermore, when academic information on the pharmacological and biologically active effects of Hopfenmehl components is used on a scientific basis, the author also considers the future development of Hopfenmehl as a therapeutic drug and pharmaceutical resource. Method: 1) The author searched for the standards and tests of Hopfenmehl listed in EP3.0 (1998) to EP10.0 (2020) and BP2000 to BP2022. 2) The author then extracted academic literature on the components of Hopfenmehl, and investigated the pharmacological and biological activity effects of Humulone, Isohumulone (isomer of Humulone), Lupulone and Xanthohumol, which are the components of the Hopfenmehl specified in EP and BP published therein. Results: 1) The standards and test methods for Hopfenmehl specified in EP3.0 (1998) and BP2000, which first listed Hopfenmehl, have been continued and maintained until today's EP10.0 (2020) and BP2022. 2) From the literature search, it was found that there are various pharmacological and biological activity effects for the components of Hopfenmehl specified in EP and BP.

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Purpose : Dr. Joseph A. Oddis (Dr. Oddis), the second Chief Executive Officer (CEO) of the American Society of Heath-System Pharmacists (ASHP) for 37 years, passed away on February 24, 2021, at the age of 92. This paper investigates the history of Dr. Oddis’ activities in ASHP and his influence and contributions to Japanese pharmacists. Methods : The life, career, and accomplishments of Dr. Oddis are summarized in primary sources and in American pharmacy in the twentieth century, Gregory J. Higby; Joseph A. Oddis: influences and achievements, C. Richard Talley and Mary Jo Reilly, Am J Health-Syst Pharm, 1997; 54: 1815-25; In Memoriam: Joseph A. Oddis, Am J Health-Syst Pharm, 2021; 78 (16): 1449-1536; Joseph A. Oddis. The next five years of the ASHP--a projection, Am J Hosp Pharm, 1967; 24: 164-69; the ASHP website; and the book 150 Years of Caring (A Pictorial History of the APhA), Hospital Pharmacists, APhA Publications, 2002; p.55-58. Results : This study introduces the improvements made in ASHP work standards, a national survey of hospital pharmacy practice, educational services, continuing education, expansion of residency training, drug information, clinical pharmacy, and the concept of Pharmaceutical Care, Pharm.D., as a professional degree for pharmacists, and contributions to the expansion of the role of pharmacists working in pharmacies. Dr. Oddis also promoted the hiring and training of pharmacy technicians. These efforts of the ASHP have contributed to influencing the residency accreditation standards in the Japanese system of professional pharmacists, and have in no small way served as a reference and contributed to improving pharmacist education and practice in Japan. Conclusion : Dr. Oddis' work at ASHP provided valuable suggestions on policies, standards of practice, and activities for the better development of pharmacist practice in Japan as a pharmaceutical professional. Especially under the leadership of Dr. Oddis, many reports on themes and committees were published and contributed to the development of medical pharmacy.

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Purpose: Toshodaiji (Toshodaiji Temple) was founded by Ganjin (Jianzhen), who was skilled in Chinese medicine and pharmacology. Additionally, despite being blind, it is said that he was able to tell different drugs apart using his sense of smell, taste, and touch. Today, the Yakuen (medicinal herb garden) on the grounds of the temple has been restored and is partly open to the public. The aim of this study is to investigate the background of establishing the garden. Method: In addition to old books, other literature and reports, the author investigated the surviving texts at Toshodaiji Temple and conducted interviews with relevant persons. Results: The Yakuen at Toshodaiji Temple was established in 1988 as a passion project of the temple's 81st elder, Kyojun Morimoto. However, it was closed in 1999 for major repairs to the main hall, which was called as the major Heisei era repairs. This required the garden to be used as a holding area for the three Buddha statues normally housed in the temple. During this closure, part of the park was transplanted to Gifu Prefecture for safekeeping, where it remained there for many years. In 2018, a plan to restore the Yakuen was proposed at the request of the 88th elder, Myogen Nishiyama. In March 2022, the part of the Yakuen that had been transplanted to Gifu Prefecture was relocated back to Toshodaiji Temple. The Yakuen is scheduled to be fully restored by 2024, with work having already begun in April 2022. Conclusion: The Yakuen medicinal herb garden at Toshodaiji Temple had to be closed at one point due to temple maintenance work, but has been partially restored since 2022.

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Objective: Advances in comparability (biosimilarity) evaluation techniques and trends in regulations and approvals in Japan and abroad were examined. Methods: The data was collected from the National Institute of Health Sciences (NIHS) Annual Report, the Pharmaceuticals and Medical Devices Agency (PMDA), and the NIHS Division of Biological Chemistry and Biologicals website. Advances in biosimilar evaluation techniques and trends in regulations and approvals in Japan and abroad were examined. Results and Discussion: The European Medicines Agency(EMA) has continuously published quality guidelines (GLs), non-clinical and clinical study GLs, and product group-specific non-clinical and clinical GLs since 2005. In Japan, the guidelines to ensure the quality, safety and efficacy of biosimilar products (Pharmaceutical and Food Safety Bureau Notification, No. 0304007) was issued by the Ministry of Health, Labour and Welfare (MHLW). In the U.S., a law was passed in 2010 setting forth regulatory requirements for biosimilars, and in 2012, the FDA released a draft guidance. Comparability studies including bioassays are needed to demonstrate that a biosimilar product has no meaningful differences when compared with the reference product. In the comparability, N-linked glycan profiles, the antibody-dependent cellular cytotoxicity (ADCC) activity of antibody drugs, and FcγRⅢ, a binding activity, are often important. The NIHS is also conducting research on related evaluation methods. Among the most important biological characteristics of monoclonal antibodies (mAbs), it is necessary to compare the Fc-mediated functions that induce immune-cell activation. The evaluation methods for biosimilars have been being developed since 2013. A generic bioanalytical method was developed to quantify therapeutic IgG1 mAbs in mouse sera by combining an easy, sample preparation method with LC/MS using selected reaction monitoring. In Japan, 32 products including cytokines, erythropoietins, antibodies, etc. were approved and have been used to date.

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Summary Introduction: In this study, the author investigated Gonzaemon Shimura, a pharmacist who provided disaster medical support following the Yamanashi Great Flood of 1907. Methods: The author used materials from the National Diet Library's Digital Collection, Tokyo University of Pharmacy and Life Sciences Library, Tokyo Metropolitan Archives, National Archives of Japan, and official records of the Yamanashi Prefecture and Yamanashi City governments. Results and Discussion: Yamanashi Prefecture is surrounded by mountains on all sides, and in the case of a disaster, it takes much time for relief supplies to arrive there from other prefectures. During the Great Yamanashi Flood of 1907, Gonzaemon Shimura provided medical support to the disaster victims not by supplying medicines, but by producing and distributing drinking water. This case is an early 20th century example of a pharmacist who was able to exercise his professional duty during a disaster at a time medicines were unavailable.

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The cosmetic products from the Japanese company Kocho-en were the first Japanese lead-free whitening cosmetics recognized by the Imperial Family. The creator of these products was the chemist Nakahiko Hasebe, who studied chemistry in France. After years of research, he presented a whitening cosmetic powder based on zinc oxide to the Imperial Court in 1900. Four years later, he named it Misono Oshiroi as a commercial product. This article describes the success of the company's early times through a rare advertising booklet by two major Japanese pharmacists (Junichiro Shimoyama and Yoshizumi Tahara) that certified Misono cosmetic products harmless. The sales competition for whitening cosmetics and the import of European cosmetic products are also discussed.

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