Kampo Risk Management Based on a Survey on Incident and Accident Cases at Specialized Kampo Medicine Facilities / 日本東洋医学雑誌

The Medical Safety Committee has conducted various activities for patient safety in Japanese traditional Kampo medicines. In this study, we conducted a questionnaire survey to promote the prevention of medical accidents and their recurrence. We received responses from 15 of 19 facilities specializing in Kampo medicine and collected a total of 247 incident and accident cases in the field of Kampo medicine. Cases of side effects included interstitial pneumonia caused by Kampo prescriptions containing Scutellariae Radix, aconite poisoning, and licorice-induced pseudoaldosteronism. Furthermore, we also collected decoction-specific cases, which are unique to facilities specializing in Kampo medicine, for the first time. From the results, we included the following seven points for risk management in the field of Kampo medicine : 1) insufficient recognition to the side effects of Kampo medicines, 2) misunderstanding of the dosages of Kampo products, 3) errors due to similarities in Kampo formulas and crude drug names, 4) preconception of frequently used Kampo prescriptions, 5) contamination in the decoctions, 6) errors related to crude drug items and their dosages that are frequently added or subtracted, 7) errors in hospital wards.

Historical Study on the Usage and the Name of Crude Drug “Valerian” in Japan / 日本東洋医学雑誌

Japanese valerian root (kanokoso, the dried root of Valeriana fauriei) has been known as a substitute for European valerian root (the dried root of V. officinalis). However, the usage of Japanese valerian root and the change of its crude drug name from ancient times in Japan have not been clear. We investigated ancient literatures, and revealed that Japanese valerian root might be used as folk medicine with the name of Japanese nard (wakansho) in the mid Edo period. Similar to the usage of European valerian root, Japanese valerian root had been used in the treatment for hysteria specifically in the late Edo period. It is considered that Japanese valerian root began to be used as women’s home medicines since hysteria had come to be assorted in women’s medical disorders in the early Showa era. Japanese valerian root had been originally named as kesso. However, kesso had been recognized as European valerian root since the plant name of V. officinalis was translated into Japanese as kanokoso in the late Edo period. In the early Showa era, the name of Japanese valerian root was changed into kissokon, and the Japanese nomenclatures for both Japanese and European valerian roots became recognized separately. After World War II, the description of kanokoso changed from kanji into katakana characters in Japanese.

Draft Standardization for Crude Drug Efficacies Prescribed in Ethical Kampo Formulation / 日本東洋医学雑誌

The usage of Kampo medicine has been expanding in hospitals and pharmacies, and the systematic education on Kampo medicines and their components is urgently needed. Although the efficacies of Kampo formulations are approved at the national level, those of the composing crude drugs are not approved individually except for some cases. Consequently, the efficacy description of individual crude drug in textbooks differs much depending on the authors. To clarify this situation, we suggested the standardized description of the efficacy of crude drugs used in ethical Kampo formulation using terms of modern Western medicine in the previous study. In this study, we reviewed the descriptions of efficacies using the terms of Kampo medicine in the books published in Japan from the 17 century to the present to explore the possibility of standardizing the crude drug efficacies using the terms of Kampo medicine. The proposal for standardized description of the efficacy of crude drugs was based on the high frequency of appearance of the terms in successive books.

Comparison of the Names and Origins of Crude Drugs Used in Ethical Kampo Extract Formulation and Listed in the Western Pharmacopoeias with Those in the Pharmacopoeias of East Asian Countries / 日本東洋医学雑誌

Following the Chinese-led global standardization of Chinese medicine, the 9 th edition of the European Pharmacopoeia, published in 2016, listed 66 kinds of crude drugs that are used in traditional Chinese medicine. By the spread of dietary supplements in the United States, the number of herbal medicines listed in United States Pharmacopoeia is tended to be increasing. In this article, we compare the names and origins of crude drugs listed in the European and American Pharmacopoeias and used in ethical Kampo extract formulation with those described in the pharmacopoeias of Japan, China, Taiwan, and South Korea. There were 4 crude drugs that had the same origins and names in the pharmacopoeia of these 6 countries, but only Coix Seed had the same English name. The pharmacopoeia of the 5 countries except the United States had 19 crude drugs with the same origin, but only Platycodon Root and Eucommia Bark had the same English and Latin names. For other crude drugs, the names and origins in the pharmacopoeia of each country were different. When scientists in each country disseminate the information about crude drugs used in their own countries to the world, it is necessary for them to describe the original plant scientific names and their medicinal parts that are unified by International Code of Nomenclature for plants instead of English or Latin names of crude drugs.

Medical Safety Committee Report :Medical Accident Information and Minor Incidents from Medical Institutions Related to Kampo Products / 日本東洋医学雑誌

The Medical Safety Committee analyzed the case reports of minor incidents from the pharmacies last time as part of an activity to promote patient safety in Japanese traditional Kampo medicine. This time, we analyzed the case reports of medical accidents and minor incidents from the medical institutions. We extracted 626 reports related to Kampo products from the public database, which the Japan Council for Quality Health Care has established based on the collected information related to the medical accidents and minor incidents. The medical accident information includes case reports related to drug-induced liver injury. The minor incident reports include prescribing error due to misinterpretation related to the quantity of one sachet of Kampo extract product, dispensing error due to similarity of product appearance, number or name, and administration error due to judging the medicine only by Kanji characters or product company names without checking the Kampo formula name. Additionally, the minor incidents were often discovered by people belonging to different professions or patients themselves. In order to promote patient safety, knowledge about these incidents should be shared among the people involved in the same or different professions.

The Significances of Water Volume to Decoct Formulas Described in Classical Chinese Medicine / 日本東洋医学雑誌

Although the descriptions of shigyakukachotanto in “Waitaimiyaofang” and tsumyakushigyakukachotanjuto in “Songban Shanghanlun” are quite similar to each other, the specifications of the dosages of crude drugs and the water volume in the books were considerably different. Focused on the specified water volume to decoct these formulas, each reasonable decocting period was estimated, then the decoctions were prepared using hard water that was common in mainland China. The dosages of aconite root were 2­-fold different between these two formulas, but the contents of aconitine-­type diester alkaloids (ADA) in both decoctions were found in the range of 1.2—1.4­-fold. It was suggested that in order to control the efficacy and the safety of aconite, the decocting period was well regulated by the specification of water volume for decocting at this ancient era. Moreover, the dosages of aconite root and glycyrrhiza in bukuryoshigyakuto (BSGT) formula of “Songban Shanghanlun” are equal to those of shigyakuto (SGT) but the specified water volume to begin decocting is as about twice as that of SGT. When prepared using hard water, BSGT resulted to make the contents of ADA lower and those of non-­ester alkaloids higher compared with those of SGT decoction. It was suggested the spe­cific water volume for each formula prescribed in classical Chinese medicine had considerable significance to determine the dosages of chemical ingredients in the decoctions especially in the circumstances using hard water to prepare them.

Representative Side Effects Caused by Kampo prescriptions :Pseudoaldosteronism, Drug-induced Liver Injury and Drug-Induced Lung Injury / 日本東洋医学雑誌

The Japan society of oriental medicine created a committee of medical safety in 2017. The first activity was to summarize the representative side effects of Kampo medicine and to enlighten members of our society about them. In this report, we documented the knowledge to keep in mind at present on pseudoaldosteronism, drug-induced liver injury, and drug-induced lung injury. Since these three major side effects may cause clinically severe conditions, it is very important to detect them early and take appropriate measures. Therefore, proper examinations at the right time are necessary while taking Kampo medicine.

Difference of the Definitions of “Ginger” and “Processed Ginger” Between the Edo Era and the Present in Kampo / 日本東洋医学雑誌

Kampo physicians in the Showa era, such as ARAKI Seiji and OTSUKA Keisetsu, had called raw ginger as the herbal medicament “ginger”, and processed or unprocessed dried ginger as the medicament “processed gin­ger”. However, many Kampo physicians in the present Japan call unprocessed dried ginger as the medicament “ginger”, and processed dried ginger as the medicament “processed ginger”. The aim of this study is to investi­gate the background of the process of this change from the Showa era to the present. We searched the defini­tions of the medicaments “ginger” and “processed ginger” in successive Japanese Pharmacopoeia editions and other related books describing these definitions. In Japanese Kampo medicine before the Showa era, the herbal medicament “ginger” had referred to raw ginger, and the medicament “processed ginger” had referred to proc­essed or unprocessed dried ginger. However, after the Heisei era, the medicaments “ginger” and “processed ginger” have referred to unprocessed dried ginger and processed dried ginger, respectively. And the raw ginger has been called as “preserved ginger”.

Committee for Medical Safety Report : Example of Minor Incidents in the Preparation of Kampo Products in Pharmacy / 日本東洋医学雑誌

We collected and analyzed the case reports of minor incidents in the preparation of Kampo products in Japanese pharmacies in order to manage the medical safety control in Japanese traditional Kampo medicine. We extracted 2,166 reports that are related to Kampo products from the database of minor incidents in pharmacies supplied from The Japan Council for Quality Health Care from 2009 to 2019. Among the reports, we found the cases that pharmacists could find the mistakes about the name, dosage and administration of Kampo products or could prevent the appearance of adverse reaction when pharmacists check the prescription and ask prescription question for doctors. It is suggested that the system of separation of dispensing and prescribing functions would be well working in medical safety control. At the same time, we also found many cases that pharmacists have actually made mistakes by confusing the name of Kampo products and dosage. In this report, we summarized the cases of these minor incidents and frequently appearing confusions about the names of Kampo products.

The Decocting Time and the Contents of the Aconitine-type Diester Alkaloids in the Decoctions of the Formula Containing Unprocessed Aconite Root in “Songban Shanghanlun” / 日本東洋医学雑誌

We investigated the decocting time to prepare the formulas containing unprocessed aconite root, such as shigyakuto, tsumyaku shigyakuto, and kankyobushito, which had been registered in “Shanghanlun” edited in Song Dynasty, using the weights and measures in Houhan Dynasty when the original “Shanghanlun” was regarded to have been established. Also the contents of aconitine-type diester alkaloids (ADA) eluted from unprocessed aconite root in the decoction were analyzed in time-dependent manners. As regards the modified formula for the “physically strong patients” in the texts of tsumyakushigyakuto in “Shanghanlun”, adding dried ginger was found to lead the decocting time to be shorter and the sum of ADA content in the decoction of the modified formula to increase about 20%. It was also found that the compositions of diterpene alkaloids derived from aconite root in kankyobushito decoction were highly different from those in shigyakuto decoction, containing less ADA and more aconine and hypaconine, due to the high pH of the decoction, which was the consequence of lacking glycyrrhiza in kankyobushito formula. It is suggested that the doctors in the era of “Shanghanlun” establishment may have carefully adjusted the contents of ADA in the decoctions using unprocessed aconite root by choosing co-decocted crude drugs.

Influence of Water Properties on the Contents of Aconitine-Type Diester Alkaloids in the Decoctions of Unprocessed Aconite Root / 日本東洋医学雑誌

The decoctions of unprocessed aconite root (uzu) were prepared with the tap water samples collected in Tianjin and Shanghai in China, and the contents of alkaloids in the decoctions were compared to those prepared with purified water or with tap water collected in Niigata, Japan. The contents of aconitine-type diester alkaloids (ADA) in the decoctions prepared with tap water collected in China were significantly lower than those with purified water or tap water in Niigata. It was speculated that this difference appeared by buffering effect of bicarbonic anion in tap water in China to decline pH of the decoction. When uzu was decocted with glycyrrhiza, ginger, or jujube, the contents of ADA in the decoctions exhibited the tendency to have higher levels than those prepared using unprocessed aconite root singly, and also this tendency was observed more remarkably when the decoctions were prepared with tap water collected in China. It was suggested that even the decocting period was fixed, unexpected change of the contents of ADAs might be induced by the differences in the properties of water used for decoction or the crude drugs decocted with aconite root. The physicians in the era when “Songban Shanghanlun” had established may have adjusted the contents of ADA in the decoction by carefully choosing the crude drugs combined to aconite root.

Implications of the Origin of “Gui” in the “Bencaojingjizhu” / 日本東洋医学雑誌

Crude drugs that feature the name “gui” have appeared in classical medicinal textbooks with different names,and the correspondence between their names and origins remains the subject of research and discussion. In the present study, we investigated these correspondences using the descriptions in the annotations of the Bencaojingjizhu and through our previous study that revealed the standards of weights and measures in this book. Based on this investigation, we strongly speculate that “gui” in the Bencaojingjizhu was the branch skin of Cinnamomum cassia (C. cassia) (corresponding to cinnamon sticks in the market), which fits with the descriptions about the length and weight of “gui” -related crude drugs in this book. We measured the contents of cinnamic aldehyde and coumarin in the branch skin of C. cassia, and compared these to contents in other crude drugs related to “gui” that can be obtained on the market. The contents of these two compounds in the branch skin of C. cassia were similar to those in the bark of C. cassia from Vietnam that meets the standards for cinnamon bark in the Japanese Pharmacopoeia and is regarded as high-grade in the market. These results support our speculation, and it might be possible that the branch skin of C. cassia can be used as medicine instead of cinnamon bark.

<b>Development of a Quick High-Yield Method for the Preparation of Decoctions, Inspired by the “Zhu san Fa” of the Song Period (Part 2)</b> / 日本東洋医学雑誌

The IPCD (Immersing Powdered Crude Drugs) method, inspired by the “zhu san fa” which was widely used in the Song period of China, has been developed to prepare Kampo decoctions quickly and easily, with highyield extract from crude drugs. One trouble with the IPCD method occurs when separating the decoction from the muddy residue of the crude drug powder. When powdered ephedra herb is packed in a nonwoven fabric bag and immersed in hot water, yield of the marker compounds is much lower than that obtained when ephedra herb powder is dispersed freely in hot water without a nonwoven fabric bag. Thus the use of a nonwoven fabric bag was shown to be unsuitable with the IPCD method. In investigating an easy and more efficient separation method, we tried decanting with a commercially available wine carafe to separate the decoction and residue. With IPCD followed by decantation using the wine carafe, yields of about 80% decoction volume were obtained as compared with those when cut crude drugs are decocted and filtered using a tea strainer, in 6 of the 7 formulas tried. We find that decantation using a wine carafe is a more practical way of separation in the IPCD method.

<b>The Investigation of Metrological Standard in “</b><b><i>Songban Shanghanlun</i></b><b>” :Focus on the Absorbed Liquid in the Decoction Residues and the </b><b>Extraction Efficiency of Ephedra-alkal / 日本東洋医学雑誌

The dosage of crude drugs described in the <i>Shanghanlun </i>has long been discussed, and a conversion ratio for 1 liang in the <i>Songban Shanghanlun </i>into modern grams has not been established yet. <i>Ekisai Kariya</i>, a bibliologist in Edo period Japan, claimed that the formulas in the <i>Songban Shanghanlun </i>could not be decocted when weighed with the “Han shu (lu li zhi)” scale (1 liang = 14 g, “regular scale”), and the weight scale in the text should be “Scale of Shen nong” (1/10 scale of the regular scale). This claim leads to the standards for Kampo prescription dosages. We inspected this matter by focusing on the amount of liquid absorbed by decoction residues, and demonstrated that the formulas in <i>Songban Shanghanlun </i>could actually be decocted when weighed with the “regular scale”. In addition, we calculated the quantities of Ephedra-alkaloids in the one-time dose of “Ma huang tang” of the several books written in the Song period, and the <i>Songban Shanghanlun </i>text, with results showing that Chinese doctors in the Song period recognized 1 liang in the <i>Songban Shanghanlun </i>as 14 grams in modern terms, and that the “regular scale” could be applied clinically. This strongly suggests that the metrological standard in the <i>Songban Shanghanlun </i>should be the “regular scale”.

The Weights in <I>Ben Cao Jing Ji Zhu</I> (Dun Huang Version) and the Volume of a <I>Fang Cun Bi</I> (One Cun Square Spoon) : Weights and Measures in the Period when the <I>Shan Han Lun</I> was Written / 日本東洋医学雑誌

For the purpose of investigating weights in the era when the <i>Shan Han Lun </i>was set forth, the weight and measures described in the <i>Ben Cao Jing Ji Zhu</i>, written in the period slightly after the <i>Shan Han Lun</i>, were studied. Some descriptions of the metrological standards are confusing in the <I>Ben Cao Jing Ji Zhu</i>. We focused on the measuring container, whose volume is equal to that of the one cun square spoon (fang cun bi), shown in the dun huang version of the <i>Ben Cao Jing Ji Zhu</i>. The volume of this measuring container was calculated on the assumption that the measures in this text follow those of the <i>Han Shu Li Li Shi</i>, and a result of 5.07 cm³was obtained. The result was confirmed by using the actual measured values of the crude drugs. The result was also considered to support measurements of the volume in the <i>Ben Cao Jing Ji Zhu </i>as following the <i>Han Shu Li Li Shi</i>. With those results, descriptions of the density of honey and lard were examined, and the weight in the <i>Ben Cao Jing Ji Zhu </i>was clarified to follow that in the <i>Han Shu Li Li Shi</i>.

<b>Differences in Water Hardness when preparing Ephedrae Herba Decoctions : Special Focus on a Comparison of Tap Water </b><b>in Japan and China </b> / 日本東洋医学雑誌

Decoctions of Ephedrae Herba were prepared using tap water sampled in Changping District, Beijing City(China), tap water sampled in Niigata City (Japan) and some mineral water samples sold in markets. Various dissimilarities were found between drug extracts prepared using tap water in Japan and China, and the extraction efficiency of the alkaloids with Beijing tap water was approximately 80% of that with Niigata tap water. It is suggested that these dissimilarities result from concentrations of temporally hard components, such as calcium and magnesium bicarbonate salts, in the water. In addition, when Zizyphi Fructus and Ephedrae Herba were decocted together in hard water, the state of the decoction, ephedra-alkaloid content included, was found to come close to that of single Ephedrae Herba decoctions prepared using soft water. It was suggested that Ziziphi Fructus might possibly play roles as a softening agent in decoctions prepared using hard water.