Pharmacological characteristics of Kampo medicine as a mixture of constituents and ingredients

Herbal medicine in Japan is termed as Kampo medicine, which is derived from traditional Chinese medicine. Shakuyakukanzoto （Shao-Yao-Gan-Cao-Tang） as a kind of Kampo formulations is composed of just two components; Paeoniae Radix and Glycyrrhizae Radix, which produced marked relaxation of intestinal tract. Mokuboito （Mu-Fang-Ji-Tang） inhibited cardiac ionic channel currents, and as a mixture also produced great vasodilatation. Sinomenine （a main ingredient of Mokuboito） as a single compound also caused the vasodilatation, but decreased it along with ageing. Gypsum containing in Mokuboito and Chotosan （Diao-Teng-San） caused more marked effects, as compared with those without Gypsum. On the other hand, Rokumigan （Liu-Wei-Wan）, Hachimijiogan （Ba-Wei-Di-Huang-Wan） and Goshajinkigan （Niu- Che-Shen-Qi-Wan） increase in order the number of contained ingredients. The formulations with more herbs （ingredients） produced much more effective actions on rat aorta, presumably due to compensation of the decline of pharmacological sensitivity with ageing. Thus, there are some important differences between single chemical drugs and mixture drugs with many ingredients. The effects of Kampo medicine （mixture） are never just a sum of each effect induced by a lot of in qredients. For elder persons, furthermore, Kampo medicine exerts more effective actions.

Effects of Kampo medicine hangebyakujutsutemmato on persistent postural-perceptual dizziness:A retrospective pilot study

BACKGROUND Persistent postural-perceptual dizziness(PPPD)is a functional disorder,typically preceded by acute vestibular disorders.It is characterized by a shift in processing spatial orientation information,to favor visual over vestibular and somatosensory inputs,and a failure of higher cortical mechanisms.To date,no therapies for PPPD have been approved.Kampo medicine hangebyakujutsutemmato(HBT)has been reported to alleviate disturbances of equilibrium.We hypothesized that HBT would be a beneficial treatment for PPPD.AIM To examine the efficacy of HBT for the treatment of PPPD.METHODS Patients with PPPD were enrolled and divided into two groups:The HBT group(n=24)and the non-HBT group(n=14).The participants completed questionnaire surveys[Niigata PPPD questionnaire(NPQ),dizziness handicap inventory,hospital anxiety and depression scale(HADS),orthostatic dysregulation questionnaire,pittsburg sleep quality index(PSQI),and motion sickness scores]before and after HBT treatment.Additionally,to identify HBT responders,multivariate regression analysis was performed using the results of the ques-tionnaire surveys and equilibrium tests;including stabilometry,and caloric,vestibular evoked myogenic response,and head-up tilt tests.RESULTS Thirty-eight outpatients were included in this study,of which 14 patients(3 men,11 women;mean age,63.5±15.9 years)received treatment without HBT,and 24(1 man,23 women;mean age,58.2±18.7 years)received combination treatment with HBT.Following HBT treatment,NPQ scores decreased significantly(baseline 40.1±10.0 vs 2 mo 24.6±17.7,P<0.001).No statistically significant changes were observed in the NPQ scores in the non-HBT group(baseline 38.6±12.2 vs 2 mo 39.4±14.4,P=0.92).Multivariable regression analysis revealed that the results of stabilometry(P=0.02)and the caloric(P=0.03),and head-up tilt tests(P<0.001),HADS(P=0.003),and PSQI(P=0.01)were associated with HBT responsiveness in PPPD patients.CONCLUSION HBT may be an effective adjunct therapy for PPPD.Patients with autonomic dysfunction,unstable balance,semicircular canal paresis,anxiety,and poor sleep quality may be high responders to HBT.

Long-term administration of traditional kampo medicine shimotsuto, juzentaihoto and unseiin inhibits experimental thrombosis in mice

Traditional Chinese herbal medicines (Kampo) are used to improve flow characteristics of blood (Oketsu). We assumed that by preventing stagnation of blood, these medicines may be beneficial not only in venous but in arterial thrombotic conditions. The present study aimed to assess the antithrombotic effect of three Kampo, using well-established in vitro and animal models of thrombosis. Western-style highfat diet containing 1% Kampo (Shimotsuto, Juzentaihoto or Unseiin) was administered to C57BL/6 mice for 12 weeks. The effect on thrombus formation by laser irradiation of the carotid artery of mice was assessed. In addition the ex-vivo technique of shear-induced platelet reactivity measurement (haemostatometry) and the in vivo test of endothelial function (flowmediated vasodilation) were also used to assess the mechanism of antithrombotic effect. All three medicines have significantly inhibited arterial thrombus formation in mice. According to our studies, the mechanism of antithrombotic effect is based on the inhibition of shear-induced platelet reac- tivity and stimulation of endothelial function (Unseiin). It is assumed that the common ingredients Japanese Angelica Root, Cnidium Rhizome, Peony Root and Rehmannia Root could be responsible for the observed antithrombotic effect.

Improvement of decocting method for Kampo medicines using a microwave oven to extend its applications in clinical practice

Decoction of Kampo medicines plays an important role in clinical practice, especially in individualized treatment, while the inconvenience and a long time requirement of the decocting process are impediments to its widespread use in Japan. In this study, we improved the decocting method by using a microwave oven such as those found in most kitchens. To validate the feasibility and safety of this new method, we decocted kakkonto, which is the most widely used formula in clinical treatment in Japan, and keishikabushito, which contains toxic components using a microwave oven. Regarding the contents of 8 characteristic components in the kakkonto decoction and the contents of 6 toxic components in the keishikabushito decoction as indices, and with the extraction and detoxification effects equal to those of the conventional decocting method as targets, we optimized the decocting conditions with Response Surface Methods. With this new method, it took 35 min to obtain almost the same extraction effect for kakkonto as with the conventional decocting method, which takes 40 min;meanwhile, it took only 45 min to detoxify keishikabushito, which takes 60 min using the conventional decocting method. Decocting Kampo medicines with a microwave oven is feasible and as safe as the conventional decocting method. It is a convenient, safe, time-saving method, and may be applied widely in clinical practice. This innovation should allow more patients to benefit from decoction and the individualized treatment it offers.

Modulation by anti-oketsu formulations in Kampo medicine of human arterial stiffness

Objective:In traditional herbal medicine(Kampo medicine in Japan),'sho'is diagnosed by the traditional assessments of clinical conditions.Among a variety of the shos,there is an'oketsu'syndrome,which is a stagnation and disturbance of microcirculation.The prompt effects of four anti-oketsu formulations in Kampo medicine on cardiovascular functions were compared in oketsu and non-oketsu persons.Methods:The arterial pulse wave from radial artery is formed by the combination with ejection and reflection pulses.An augmentation index(AI),a ration of the ejection and reflection pulses,indicates a degree of arteriosclerosis.For both seventy-six students with oketsu and thirty-seven students with non-oketsu,Kampo formulations overcoming oketsu of Tokishakuyakusan(TS,Dang-Gui-Shao-Yao-San),Kamishoyosan(KS,Jia-Wei-Xiao-Yao-San),Keisibukuryogan(KB,Gui-Zhi-Fu-Ling-Wan)and Tokakujokito(TJ,Tao-He-Cheng-Qi-Tang)were taken once,and then,the cardiovascular functions including blood pressure,heart rate,central arterial blood pressure(CBP)and AI were examined for 60 min.Results:At 40-60 min after an intake,these formulations decreased the AI almost by 6-18%(n=76),by 18.3±3.1%(P<0.01,n=15)with TJ.Simultaneously,the CBP was reduced by 9.0±1.8%(P<0.05,n=23)with KS and by 9.1±2.0%(P<0.05,n=15)with TJ.On the other hands,non-oketsu group had less or no effect by any kinds of the formulations.Conclusion:The anti-oketsu formulations can exert the ameliorative action for oketsu persons via decreasing AI and CBP.

Development and Future Trends of Traditional Kampo Medicine in Japan

Traditional Kampo medicine is based on traditional Chinese medicine,which spread to Japan via the Korean Peninsula in the 5th century.The practice of Kampo developed gradually under the influence of local Japanese culture and prospered until the Meiji Restoration.Kampo appeared in schools successively,such as the School of Later Developments,the School of Classic Methods,the School of Textual Research,and the Integrated School.However,the practice of Kampo gradually declined after the Meiji Restoration.Today,through the continuous efforts of knowledgeable Japanese Kampo practitioners,the practice of Kampo has entered a new era as an indispensable aspect of contemporary Japanese medicine.

Standards of Reporting Kampo Products (STORK) in research articles

There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials （CONSORT） checklist, we hereby propose the use of the Standards of Reporting Kampo Products （STORK） website, http：//mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.

日本汉方药物的妊娠期和哺乳期风险评估及对我国中成药的影响

目的:通过对日本汉方药物的药品说明书进行妊娠期和哺乳期风险分析,评估日本汉方药物的用药风险及其对于我国中成药妊娠期风险评估的影响,为进一步开展我国中成药的妊娠期和哺乳期风险评估提供借鉴及参考。方法:针对日本医药品与医疗器械局平台收集及整理的148种医用日本汉方药物相关药品说明书,分析妊娠期和哺乳期相关表述,评估具有用药风险的日本汉方药物及中药组分。结合我国《中华人民共和国药典:一部》(2020年版)、《中药药物警戒》和《中药药性论》等中药典籍,对日本汉方药物可能存在的妊娠期潜在风险进行评估。基于日本汉方药物妊娠期风险中药组分,对我国505种中成药进行妊娠期风险评估,分析其对我国中成药妊娠期风险的影响。结果:日本148种日本汉方药物中,存在妊娠风险的药物共39种。妊娠期风险的中药组分包括大黄、牡丹皮、附子、桃仁、牛膝、芒硝和红花,主要为自身毒性及对于流产、早产的影响。哺乳期风险日本汉方药物中,因含有大黄而易引起新生儿腹泻的药物共18种。根据我国典籍评估,日本汉方药物具有潜在风险共93种。依据日本汉方药物风险组分,我国505种中成药中具有妊娠期潜在风险的药物共59种,占345种未标注妊娠期禁忌药物种类的17.1%。结论:日本汉方药物基于妊娠期和哺乳期风险的中药组分对其日本汉方药物成药风险进行评估,其特殊人群的风险表述方法对我国中成药发展具有一定的借鉴意义。

远田裕政对《伤寒论》及汉方现代化学术思想研究

当代日本汉方学者远田裕政(1934-2003年)师从千叶古方派创始人奥田谦藏,著有《伤寒论再发掘》及《现代汉方》系列论著。本文浅略总结远田裕政于《伤寒论》研究及汉方现代化体系的经方学术思想,其对康治本《伤寒论》条文及方药研究深入,试图找到《伤寒论》条文原始状态与经方演进过程,提出药基的概念和个体病理学理论,总结现代化药证,设立基本八方分类法,以结构式图示化解构经方和后世方。远田裕政具有大胆开拓探索精神,在汉方现代化上做出勇敢的尝试,中医现代化发展亦要求进行核心理论的现代化,促使中医更好地走向世界。

名古屋玄医与日本汉方医学之自立

名古屋玄医借医学复古对金元医学的非难首次打破了中国医学在日本的权威地位,之后更是提出医道规矩,试图使汉方医学区别于中国医学而自立。从历史的角度来看,日本医界的陈陈相因是他打破原有理论的原因,构建新的医学体系的动机更多是为了证明“和胜汉”说在医学领域的成立。从学术思潮传播的角度而言,玄医很大程度上受中国的错简重订派与温补学派的启发。玄医的医学反思,打破了汉方医学对中国医学的绝对依附,其思想也深刻参与构建了古方派的医学体系。

近代日本医学范式转换的历史与逻辑

历史上日本长期学习借鉴中国医学并建立起了本国的“汉方医学”体系,西方传教和商贸活动将西方医学代入日本,使日本在18世纪至19世纪完成了医学领域的全盘西化过程,发生了以汉方医学逐渐消亡为结局的向西医学范式的全面转换。汉方医学的不同学派本身具有改变医学认知方式的意愿,西医学的科学性质和知识体系为医学范式的转换提供了强大的动能。西方世界的对外扩张和日本自身的社会变革,都为近代日本医学范式转换提供了条件和土壤,是医学领域内部与外部社会环境共同作用的结果。

日本汉方药企业专利布局分析——以株式会社津村为例

目的 对株式会社津村2000—2022年申请的日本专利和中国专利进行分析,了解其技术研发及专利布局方向,并挖掘其战略处方专利布局,以期对我国中药企业有所启示。方法 在Incopat专利检索数据库上检索2000—2022年株式会社津村申请的专利,对其进行专利标引及专利技术分析。结果 株式会社津村围绕汉方制剂产业链上下游技术开展专利布局,专利布局连续且技术主题丰富,对我国中药企业具有潜在威胁,战略处方专利布局具有策略性。结论 我国企业要制定灵活的专利布局策略,拓宽中药企业专利布局技术覆盖范围,持续研发投入并做好专利防御,策略性搭建重点中药产品专利网。

汉方医家浅田宗伯在日本霍乱大流行时期的贡献

浅田宗伯是日本近代最重要的汉方医家之一,他在日本霍乱大流行时期(1858—1860)的活动与贡献迄今为止未受到学界关注。本文考察了浅田宗伯在霍乱大流行时期抗击霍乱的活动。1858年7月霍乱在江户爆发后,浅田宗伯深入疫区,成功救治大量霍乱病人,撰著、刊刻霍乱应急手册《暴泻须知》供疫区民众使用。此后到1860年,浅田宗伯相继编撰了《治瘟编》、《治瘟编补》、《治瘟编考证》。其中《治瘟编》最具临床与学术价值,推动了汉方医家对霍乱的研究与讨论。浅田宗伯对真性霍乱的命名以及对霍乱病因、传播途径的认识不及清代医家,但对霍乱的诊断与治疗颇具特色。与兰医绪方洪庵对比,浅田宗伯经过临床实践,参阅中、日及西方医书后才推广他的个人经验与治法,更为谨慎。

Traditional Japanese Medicine,Kampo:Its History and Current Status

Traditional Japanese medicine,Kampo,is used by over 80%of medical doctors in Japan.Owing to its high quality and safety,Kampo has been integrated into modern medicine,and there are 345 randomized controlled trials using Kampo in Japan as of 2010.Although there are a number of articles in top journals about basic science research,we can find only small numbers of high-quality clinical evidence.Since undergraduate education on Kampo has been established,integrative approach with the balanced combination of modern medicine and Kampo is expected to generate good clinical evidence in the near future.

Effect of Saikokeishito, a Kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts

OBJECTIVE： Saikokeishito（TJ-10） is a Kampo（traditional Japanese herbal） medicine, clinically used for hundreds of years in East Asia. Among its various mechanisms elucidated so far, TJ-10 inhibits the production of transforming growth factor-β1（TGF-β1） and development of pancreatic fi brosis in vivo. Oxidative damage of normal human dermal fi broblasts（NHDFs） in the corium is a cause of human dermal senescence. Our aim was to determine whether TJ-10 protects NHDFs from premature senescence by hydrogen peroxide（H2O2）. METHODS： Premature senescence was induced in NHDFs by 200 μmol/L H2O2 for 4 h. Cell viability and the expressions of p53, AMP-activated protein kinase α1（AMPKα1）, AMPKα2, and 14-3-3 protein sigma（14-3-3 σ） were measured in NHDFs treated with TJ-10 for 48 h before exposure to H2O2 for 4 h. RESULTS： Cell viability after treatment with 200 μmol/L H2O2 for 4 h was similar（about 80%） to after pre-treatment with TJ-10. Ascorbic acid as a control did not protect NHDFs from damage by 200 μmol/L H2O2. Treatment with 200 μmol/L H2O2 tended to up-regulate p53 and to down-regulate SIRT1 and AMPKα1, but had no effect on AMPKα2 and 14-3-3 σ expression. Pretreatment with TJ-10 inhibited H2O2-induced up-regulation of p53 and enhanced AMPKα1 expression. CONCLUSION： It is suggested that Saikokeishito has a protective effect on oxidative stressinduced senescence of NHDFs.

日本“安政霍乱”时期汉方医家的研究与心得

1858-1860年日本霍乱大流行时期,長松文忠、奥田実、浅田宗伯、大村宽、高嶋久貫、马杉质、菅間元章、和爾子譲、尾台榕堂等9位汉方医家通过临床探索、参阅中国医籍、实地调研,研究和总结了霍乱的病因、病机,成功治愈霍乱并撰写了相关著作。9位汉方医家均意识到霍乱有别于《黄帝内经》等典籍中的传统“霍乱”。他们主张,霍乱源于非常之气;霍乱为外感病,多见实证,临床采用汗、吐、泻、温、清、外治等法。9位汉方医家在著作中总结各自的心得,展示他们诊疗霍乱的独到经验,主要包括:以患者的腹泻物性状、发热与否、是否腹痛区分霍乱与一般急性胃肠道疾病;尺泽及委中穴有血络隆起是霍乱将要发作的征兆,急以刺络法令泻其血,减少患者病重的可能;患者尺脉洪大,是当用生石膏之脉,尺脉沉实且腹部胀满,则是应用大黄之脉;患者剧烈的呕吐是治疗霍乱的一大难点,可用葛根加半夏汤倍生姜,或以罂粟壳为君药的济世饮,或冷服小半夏加茯苓汤,以期减缓呕吐症状,令患者能够接受后续治疗。

室町时代以来日本汉方医家治疫验案探析

室町时代以来,日本汉方医学界相继形成了后世方派、古方派、折衷派等医学流派,各流派代表人物所留存的医案记录为中医药传日后应用于日本各类疫病辨治提供了切实依据。其中,后世方派曲直濑玄朔的医案反映了其分期治疗痘疮以及针对麻疹恢复期患者扶正托邪的治疗思路;古方派吉益南涯的医案体现了其治疗疫病善用峻剂驱逐瘀热之毒以及辨疫痢虚实而治的特点;折衷派浅田宗伯的医案则呈现出其博采仲景方及中日其他各家验方而井然有序的治疫经过。此外,北山友松子、古林见宜、野间玄琢等的医案也进一步展现了近世日本汉方医家将中医方剂灵活化裁应用于疫病治疗之中。

近代汉方医学杂志视域中的民国中医药行业

民国时期是中医药从传统到现代过渡的重要阶段,通过梳理20世纪三四十年代日本汉方杂志的报道,刻画日本人视角下的中医药业态面相,揭示中日传统医界在近代转型期的探索与思考。民国时期的中医行业文化积淀深厚,药材贸易繁荣,制药工艺精湛,医界同仁锐意革新。这些认识颠覆了明治维新以来中医药落后保守的形象,展现了中医药文化的博大精深、极具特色的一面,同时奋进创新的中医界也给经历了漫长低谷期的汉方医学界极大的鼓励,为中日传统医学界的现代交流奠定了良好的基础。

张景岳医学著述的传日、受容与变容

明代医家张景岳之代表作《类经》《景岳全书》《质疑录》等曾于江户时期先后多次传日,日人除抄刻《类经》《质疑录》原著外,还对《景岳全书》进行节选与重编。不同学者主要围绕张景岳关于阴阳五行、三焦、命门、伤寒以及经穴定位等方面的论述展开争鸣与考辨,日本医家对张景岳所创制的内、外、妇、儿各科方药与针灸疗法也多有择用。通过梳理张景岳医著的传日、受容与变容,可明晰其对日本医家所产生的影响。借日本医家之眼反观张景岳医学著述,也可促进其更好地应用于理论研究与临床工作。

基于SWOT-PEST分析法探索中成药国际推广新途径

目的:基于发放的“我国中成药国际推广调查研究现状”问卷分析我国中成药国际推广现状,并以日本汉方药的推广为切入点,通过分析日本汉方药国际发展的原因,以期探索我国中成药国际推广的新途径。方法:基于SWOT-PEST分析法制作调查问卷,进行调查和分析。结果:问卷调查发现,由于缺乏有效的国际合作、存在文化差异等原因,中成药国际推广整体情况并不乐观。而日本汉方药由于政策支持、重视推广、进行技术创新等原因,在国际上取得了良好的效益。结论:我国中成药在推广过程中,应通过提升产品质量稳定性、加强市场调研、与当地医疗机构合作等途径,促进其有效地推广。