The population of dementia sufferers is estimated to reach 152 million in 2050. Dementia lays a huge burden on family members, medical staff and caregivers in addition to the sufferers themselves, and could possibly collapse the current social system. To prevent such a catastrophe, drug discovery to fight dementia is an urgent task that should be undertaken by all humanity as the 21st-century equivalent of traveling to the moonshot.
Alzheimer’s disease (AD) accounts for more than 50% of total dementia, and its three major pathologies are known to be senile plaque composed of amyloid beta (Aβ) aggregates, neurofibrillary tangle made by tau protein aggregates, and neuronal cell death commencing with cholinergic neurons. AD pathogenesis is being elucidated through pathology, genetics and biology, and these studies have led to three hypotheses.
Approaches under the choline hypothesis created three acetylcholine esterase inhibitors (donepezil, rivastigmine, and galantamine) which enhance cholinergic neuronal activity. These three medicines and memantine (NMDA antagonist) are currently available for AD treatment. They temporarily improve cognitive and daily functions but cannot slow down the progression of AD itself.
Aimed at disease modification, a number of agents based on the Aβ hypothesis have been investigated in clinical studies, but most of them have failed. Currently a few anti-Aβ antibodies are in the final stage of clinical trials and are expected to be commercialized in the near future. Following on from anti-amyloid therapy, multiple approaches including tau, microglia and synaptic/neuronal regeneration are being actively researched to cure this complex disease.
In parallel with drug discovery, less-invasive diagnostics that realize earlier detection and intervention are also being developed and have shown significant progress over the last two years.
I believe that dedicated endeavors by the scientists working in the AD field and the thoughtful support of patients in society will bear fruits to actualize healthy longevity by conquering dementia.
Dietary requirements that reduce the risk of dementia are sufficient nutrition and a well-balanced diet.
Regarding the three main types of nutrients, for carbohydrates, it is good to consume mainly low-glycemicindex foods that release glucose slowly. These include deep-colored vegetables, fruits, beans, mushrooms and seaweeds. It is also important to reduce the intake of white sugar.
For fats, it is best to consume mainly blue-backed fish, which are high in DHA, linseed oil and perilla oil, which are high in omega-3 fat, and olive oil, which is high in omega-9 fat.
For proteins, it is best to consume mainly eggs and soy beans. It is also good to consume meats and seafoods.
On the contrary, it is better to avoid soft drinks, trans-fatty acids (margarine) and too much protein.
Ursodeoxycholic acid (UDCA) is a bile acid used worldwide for improving hepatic, bile, and digestive functions. UDCA was first introduced to the world more than 60 years ago as URSOR Powder in Japan by Tokyo Tanabe Pharma Co., Ltd. (founded in 1901 by Motosaburo Tanabe). However, the origin of this medicine is even older; that is, it was an animal crude drug called “YUTAN” made from bear gallbladder.
The same as other western medicines, chemical synthesis was necessary to commercialize UDCA. It was an exceptionally rare agent that required isolation, crystallization, determination of structural formula, and establishment of an efficient synthetic method all conducted by Japanese researchers. After being commercialized, URSO was approved for additional indications of gallstone dissolution (1978), implementation of liver function in primary biliary cirrhosis (1999), and chronic hepatitis C (2007). These achievements were the result of the unflagging efforts of many researchers. Although 60 years have passed after the market launch, UDCA sales are still growing globally and high-quality bulk powder is continuously supplied from Japan to the world.
This article discusses the development history of URSO in view of the relationship with the brief history of Mitsubishi Tanabe Pharma Corporation.
Koan Ogata (1810-63), the director of Tekijuku, was a physician who contributed much to the medical profession through his knowledge of Western medicine late in the Edo period. The medicine chest he used during the prime years of his life included many yet unknown crude drugs. In order to identify the drug labeled as saru, we conducted a thorough investigation of medical literature published during the 17th to 20th centuries. As the result of pharmacognostical analysis, we clarified the morphological characteristics of sarsaparilla, which is a candidate for the origin of the contents. We then examined specimens of Mexican and South American sarsaparillas, which were collected by E. Merck and Eli Lilly & Co. at the beginning of the 20th century, using a digital microscope. We found that these specimens showed three morphological features : 1) They had cylindrical roots with diameters of approximately 5 mm, 2) their surfaces were brown with deep vertical crinkles, and 3) they had light brown cortices and white steles covered with a creamy yellow endodermis. The contents of saru showed a high similarity to the characters of sarsaparilla written in literature and the morphological features of historical specimens. We identified them as the roots of genus Smilax, including Smilax medica and S. officinalis.
Koan Ogata (1810-63), the director of Tekijuku, was a physician who contributed to the progress of Western medicine late in the Edo period. We found many kinds of crude drugs left in his medicine chest. In order to identify the origin of the drug labeled as dobuku we thoroughly investigated the medical literature published during the 16th to 20th centuries, and morphologically analyzed the contents of dobuku by making comparisons with the specimens inherited by Osaka University using a digital microscope. The literature investigation showed that dobuku means dobukuryo, and its botanical origin during the Edo period was Smilax glabra Roxb. We compared the contents of dobuku morphologically with the specimens of S. glabra and S. china L. We found that the contents have a internal morphological structure similar to that of S. glabra, which is the candidate of the botanical origin of the contents.Therefore, we believe that dobuku is dobukuryo, and its botanical origin is S. glabra. We also surveyed the clinical application of dobukuryo in medical literature and found that it was used for treating patients with syphilis during the Edo period.
Mitsuru Uchiyama, former representative director of the Council on Pharmacists Credentials (CPC), passed away in June 2019. He became president of the Japan Pharmacist Training Center (JPEC), which supports and promotes continuing education (CE), and later became the representative director of the newly established independent evaluation agency, CPC, which evaluates and accredits pharmacist certification programs. He explained the necessity of CE and credentials, which are objective proof of the results of CE, and made a great contribution to the development of CE.
Purpose: This paper reviews the history of CE for pharmacists in Japan, “in memory of Mitsuru Uchiyama, Ph.D.,” and examines the background and issues leading up to the current situation today.
Method: Information on CE for pharmacists and various certification programs are investigated using websites, books, and other materials.
Results: The CE for pharmacists in Japan began systematically in 1989 with the establishment of JPEC. CE programs were started in 1994, special training programs were introduced in 1998, and pharmacy specialties programs were added in 2005. After that, based on the needs expressed from the medical side, many academic and professional pharmaceutical organizations have created special training and pharmacy specialties programs in various fields. Currently, the number of programs exceeds 30. CPC, established in 2004, has evaluated and accredits pharmacist credentialing programs that meet the evaluation criteria. To date, it has certified 32 programs, mainly CE programs. Uchiyama carried 70 columns, which can be called
the “CE theory” on a website, and made it a message to pharmacists.
Conclusion: The CE for pharmacists is developing steadily, but there are several problems. Special training and pharmacy specialties programs have issues regarding the level and uniformity of programs, and independent evaluation is required. The number of credentials in CE programs has increased rapidly in recent years in connection with medical fees. There is a tendency to easily obtain credentials in some pharmacists, so correction is necessary. It is hoped that we pharmacists will learn from the messages left by Uchiyama, such as the basic principles of CE, and utilize them in our own CE.
Niigata Prefecture is one area of Japan that witnessed large-scale population and economic growth during the Meiji Period (1868-1912) when modern pharmacy was introduced from the west.As a result, Niigata had more pharmacists than other prefectures, and its pharmaceutical businesses flourished.
In the first decade of the Meiji Period, a medical school was founded, to which a pharmacy school was later added. This was one of the earliest schools of pharmacy in Japan. In the second decade of the Meiji Period, two pharmaceutical journals were published. These journals introduced modern pharmaceutical science and were equal in status to those published in Kyoto and Kobe. Two societies were founded: Niigata Pharmaceutical Association in 1882 and Niigata City Pharmaceutical Association in 1901. The production and distribution (peddling) of medicines also took place on a wide scale in Niigata. The Niigata School of Medicine
was founded in 1910, where some pharmacists gave lectures on chemistry and worked in the school's hospital.
During the Meiji Period, Niigata was one area of the country where modern pharmaceutical science had achieved progress.
Objective: To study if Japanese new-biopharmaceuticals (1985-2016), including nine hormones and cytokines, three enzymes, one other medicine, and three antibody medicines originating in Japan, were approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) authorities.
Results and Discussion: Of the nine hormones and cytokines, the Ministry of Health and Welfare, Japan (MHW) approved the use of Mecasermin on October 5, 1994 and the FDA approved its use on August 30, 2005. Mecasermin is given for the long-term treatment of growth failure in children with severe primary insulin-like growth factor (IGF) deficiency or with growth hormone (GH) gene deletion. None of the three enzymes and one other pharmaceutical were approved. The three antibody medicines were approved by the Ministry of Health, Labour and Welfare, Japan (MHLW) / the Pharmaceuticals and Medical Devices Agency (PMDA) as follows: The EMA approved the use of Tocilizumab as a rheumatoid on January 16, 2009, and the FDA approved use on August 1, 2010. The FDA approved the use of Mogamulizumab for the treatment of relapsed or refractory mycosis fungoides (MF) or Sezary syndrome (SS) on August 8, 2018. The FDA approved the use of Nivolumab for the treatment of melanoma on December 22, 2014 and for the treatment of metastatic squamous non-small cell lung cancer on March 4, 2015. The EMA approved the use of Nivolumab for four types of treatment on June 19, 2015.
In this article, I analyzed why the 12 other biopharmaceuticals were not approved by the FDA and/or EMA. The importance of the ICH guidelines for adapting new GCP(E6) in 1998, and that of the quality of biotechnological/biological products are discussed. The establishment of the PMDA in 2004, and history of enhancing the transparency of the review process are also discussed.
Asafetida was once used to calm down mental excitement such as hysteria. It was listed in Japanese pharmacopoeia (JP) and other foreign pharmacopoeia such as USP, BP, and DAB. However, after World War II, Asafetida disappeared from each country’s pharmacopoeia. In addition, it can no longer be found in today's herbal medicine academic books in Japan.
In this study, the author investigated the specifications and test methods of Asafetida listed in JP, USP, BP and DAB. He also investigated the ingredients in the academic literature of pharmacology and chemistry from 1860 to 1920. As a result, it was revealed that ferulic acid (FA) is abundant as a resin component of Asafetida.
FA is widely distributed in plants, and has a variety of physiological and health benefits. Today, it is in the academic spotlight. Among the reasons is the belief that the inhibitory action of FA on Aβneurotoxicity is expected to improve cognitive function and suppress its progress in Alzheimer-type dementia in cooperation with the inflammation inhibitory action of specific coumarin compounds. Additionally, the author believes that seeking Asafetida as a source for FA is one measure. If Asafetida has the potential to be used effectively as a FA resource, it is necessary to verify how much the effect of FA reflects the effect of Asafetida.
In this report, the author proposes the phrase, Philosophy of Pharmacy.
In Japan, such a phrase has scarcely been used by pharmacists because they have considered medicines and drugs as materials and have not focused on their patients enough. As a way for pharmacists to consider their patients more, the author recommends the following two philosophies:
1. Revision of the Pharmacists Act
Article 1: A pharmacist is to contribute to the improvement and promotion of public health by dispensing of medicine, and supplying medicines and other pharmaceutical health and sanitation services, thereby ensuring citizens lead healthy lives. The above, Article 1, needs to be revised by adding the following sentence.
In addition, pharmacists should observe the new code of ethics for pharmacists introduced in 2018, and sympathize with patients to contribute to their medication.
2. Fully Consider Patients' Needs
The author made a figure illustrating the relations between natural science（pharmacy），cultural science, social science and cultural art with care taken to fully consider the needs of the patient.
[Objective] This treatise is a part of a study on how self-medication should be supported by pharmacists.
Self-medication is gaining attention as the result of rising medical expenses in Japan. On the other hand, I think it is important for people to protect their health autonomously. We need to clarify how pharmacists, as professionals, support self-medication.
[Methods] We researched the actual situation of placement medicines by reviewing 59 records from one of the placement medicine suppliers (Y) in former Niwa County, Aichi Prefecture. We focused on a placement medicine, because it is said that the medicine had played an important role as a form of self-medication during the Taisho to early-Showa eras before the establishment of Japanese national insurance. We reveal the name and the prescription of the medicine that was sold by the placement medicine supplier.
[Results] The medicines managed by Y and how they were changed have been clarified. In addition, historical influences related to them were recognized.
[Conclusions] (1) The company managed balanced home medicines. An investigation should be conducted to examine whether or not the list is generalized.
(2) The Home Medicine Sales Act has changed private companies. Further investigations covering a wider area are required.
(3) Article 6 of the Home Medicine Sales Act stipulates that sales are made by pharmacists. However, the pharmacist was not actually involved. An investigation should be made into why pharmacists were not needed on-site.
(4) No effect of policy shift from invalid harmless to effective harmless. The impact of effective harmless policies should be investigated.
(5) Quinine was commonly used. Knowing more will give us clues about illnesses and how people were treated at that time
The University of Tokyo has 30 libraries and reading rooms, including the Pharmaceutical Sciences Library. Each library and reading room has a large number of collections, and the Pharmaceutical Sciences Library also has a collection named the History of Pharmacy Library.
The History of Pharmacy Library was established at the Pharmaceutical Sciences Library at the request of the Japanese Society for History of Pharmacy in March 1998 and was donated by the Japanese Society for History of Pharmacy to the Faculty of Pharmaceutical Sciences, The University of Tokyo in April 1999.
Initially, the use guide was enacted and the collection list was made public; however, it then remained unorganized for more than 16 years.
At the end of 2015, the collection was finally reorganized in cooperation with the Pharmaceutical Sciences Library and the Japanese Society for History of Pharmacy and became available for research use again.
In this paper, the history of the establishment, process of rebuilding, composition of the collection, and future issues to help many researchers make effective use of the History of Pharmacy Library are described.