Activities for Collecting and Providing Information

We are aiming at “Contributing to creating a healthcare environment where all patients can receive treatment that includes “Kampo” medicine where appropriate in any healthcare institution or medical specialty in Japan.” To achieve this target, we have been supporting Kampo medicine education for medical students at university medical departments and medical colleges, study sessions on Kampo for physicians-in-training at designated hospitals for clinical training, and conducting various Kampo seminars and promotion activities for medical professionals continuously in an organized manner.

Activities for Collecting and Providing Information

Categories/Types of Crude Drugs of Tsumura

Establishment of Kampo Medicine

To promote the establishment of Kampo medicine, we untiringly lobbied 80*1 university medical departments and medical colleges throughout Japan to require students to attend Kampo medicine lectures, to hold on-campus study groups as a venue for human resources development in order to produce lecturers in Kampo medicine education, and to establish Kampo outpatient clinics*2 for clinical practice at university hospitals. As a result, all 80 university medical departments and medical colleges throughout Japan began to offer Kampo medical education by FY2004. Today, Kampo medicine education is a requirement at almost all universities, and Kampo outpatient clinics have become available. Thus, Kampo medicine education has become better established at universities.
In order to have a greater number of physicians incorporate Kampo medicine in their treatments, it is important for us to continue providing support to consistent Kampo medicine education before graduation, immediately after graduation, and post-graduation.

※1Excludes two newly established universities
※2Kampo outpatient clinics: Outpatient clinics specializing in Kampo medicine that perform medical examinations and offer treatment based on Kampo medicine

Activities for Providing Information to Medical Practitioners

Promotion of information provision activities

Tsumura has provided nationwide web-based lectures, and the number of doctors viewing them is increasing.
In area activities, we fine-tune the information to be provided, taking into account the characteristics of each area and facility. Each sales office also holds events to meet the needs of doctors who want to learn about Kampo medicine.
MRs also actively hold events and are now implementing new activities tailored to the situation of each geographical and medical area.
We have significantly increased the number of web-based seminars, aiming to promote hybrid activities using both online and in-person activities.
Additionally, we are enhancing e-promotions to deliver information in the form and content that doctors need.

The Origin of Our Activities

Our prescription Kampo products were listed in the National Health Insurance drug price standard (NHI drug price standard) in 1976 for 33 prescriptions. In the years following, the number of prescriptions in the NHI drug price listing gradually increased to reach 129 prescriptions in 1987, where it has remained until today. Following the listing of prescription Kampo products in the NHI drug price standard, the sales of those products increased steadily, reaching approximately 100 billion yen in FY1991. Shortly after, a problem involving adverse events occurred in relation one of our major products, Shosaikoto. Fears and doubts about safety became widespread, and overall sales of prescription Kampo products dropped. Meanwhile, adverse events involving Kampo medicines were not well recognized by medical practitioners. While the use of Kampo products had been increasing, the actual practice of “Kampo medicine,” including diagnosis based on Kampo medicine, and its effectiveness and safety were not sufficiently understood by medical practitioners and the general public, and this was a factor in the incident. Following this incident, we made big changes to our business policy and executed various measures such as the “Establishment of Kampo medicine,” started in FY1997, and our “drug fostering” program in FY2004. In FY2016, the sales exceeded 20 million units (volumebased actual sales).

Trends in results of 129 prescriptions of kampo medicine for medical use (actual sales* volume growth)

Expansion and Stable Growth in the Kampo Market

Strategy for Expanding the Kampo Market

As our basic strategy for expanding the Kampo market, we have identified three important domains in which to focus our activities: the “Geriatric field,” the “Cancer domain (supportive care),” and the “Gynecology field.” We are continuously providing information in these domains on basic and clinical evidence, treatment guidelines on Kampo practice, and the use of prescriptions based on Kampo medicine.

In these three important domains, we are engaged in important issues such as medical needs for diseases characterized by low satisfaction levels with current therapies. Specifically, within these three domains we will seek to expand sales of prescriptions for BPSD*, frailty, supportive care in cancer, menopausal disorders, etc.

BPSD: Behavioral and Psychological Symptoms of Dementia (such as excitement, restlessness, sleep disorder, etc.)

Improving Evidence Package

“Evidence package” refers to providing quality package inserts and publishing information in treatment guidelines as well as organizing clinical evidence, action mechanism, monitoring of adverse drug reaction frequency survey, ADME (Absorption, Distribution, Metabolism and Excretion)*, and health economic data. Clinical evidence refers to meta-analysis data (analyzing data with higher statistical power by aggregating multiple study outcomes) and randomized control test (RCT) data.

ADME: Abbreviation of Absorption, Distribution, Metabolism, and Excretion. It is a way of observing the pharmacokinetics of a drug in an organism after administration.

	Prescription name/ Product No.		Meta analysis	RCT	Action mechanism	Monitoring of adverse drug reaction frequency survey	Absorption, Distribution, Metabolism and Excretion (ADME）	Health economic data	Published in treatment guidelines
“Drug fostering” program formulation	Daikenchuto	TJ-100	3	31	〇	〇	〇	〇	Pediatric chronic functional constipation disease, Systemic Sclerosis
	Yokukansan	TJ-54	4	14	〇	〇	〇	〇	Dementing illness, Use of psychotropic drugs for BPSD for primary care physicians (2nd edition)
	Rikkunshito	TJ-43	1	21	〇	On-going	〇	-	Functional gastrointestinal diseases, the diagnosis and treatment of psychosomatic diseases, Gastroesophageal reflux disease, Systemic Sclerosis
	Goshajinkigan	TJ-107	2	14	〇	-	〇	-	Benign prostatic hyperplasia, Overactive bladder syndrome, The pharmacologic management of neuropathic pain
	Hangeshashinto	TJ-14	1	7	〇	-	-	-	-
“Growing” formulation	Hochuekkito	TJ-41	-	12	〇	-	-	-	Female lower urinary tract symptom
	Shakuyakukanzoto	TJ-68	-	11	〇	〇	〇	-	Amyotrophic lateral sclerosis (ALS)
	Bakumondoto	TJ-29	-	5	-	-	-	-	Cough, EBM practice guidelines for asthma
	Kamishoyosan	TJ-24	-	4	-	-	-	-	Diseases in obstetrics and gynecology, the treatment and diagnosis of psychosomatic disorders
	Goreisan	TJ-17	-	7	-	-	-	〇	Chronic headache

Elucidation of Kampo Medicines by New Technology

Due to their nature as compound products containing multiple plant-based components, the scientific elucidation of Kampo medicines has been considered difficult. However, as a new major theme, we will conduct research to demonstrate the usefulness of Kampo products, including the elucidation of action mechanisms of multiple ingredients and verification of health economic impacts in addition to clinical research and the accumulation of a body of evidence to demonstrate effectiveness and safety. In recent years, research into and analysis of Kampo medicines has been advancing thanks to the development of new technology owned by leading academic institutions such as the University of Tokyo

Major new technology	Elucidation items
System biology*1 →	Multi-component network*2
Metabolomics*3 →	Biomarker*4
Analysis of intestinal flora*5 →	Responder, non-responder*6
Utilization of big data*7 →	Health economics

※1System biology: A biological approach to elucidate the relationships among individual organisms and genes and their various roles through the use of artificial intelligence (AI), physiological approaches, and biotechnology to achieve an integrated understanding, as opposed to analyzing individual biological functions.
※2Multi-component network: Kampo medicines are considered to exhibit medicinal efficacy due to their having multiple components that act on different parts of the body. A multi-component network is an action mechanism to show the relationship of those components by analyzing them in a comprehensive manner.
※3Metabolomics: A method of analyzing metabolic substances using mass spectrometry, etc. It is performed because the types and quantities of metabolic substances within an organism change due to external stimulants such as environmental changes in temperature and light as well as the ingestion of food and drugs. This is a research domain applicable to the diagnosis of diseases.
※4Biomarker: A biological factor that enables physicians to evaluate the disease state, change, and degree of recovery or healing.
※5Analysis of intestinal flora: Analysis of the origin of the wide variety of microbes and bacteria in the intestine through the use of investigative methods and technologies.
※6Responder, non-responder: A person for whom drugs are effective, and for whom drugs are not effective.
※7Utilization of big data: The use of huge volumes of ordinary medical data in epidemiological studies for the assessment of quality of medical care, analysis of health economics, etc.

Basic and Clinical Research on Five “Drug Fostering” Program Formulations

Daikenchuto	Target disease and symptoms An abdominal bloating from illness such aspost-operative ileus (intestinal paralysis), etc. Overview In 2007, the DKT Forum was organized to establish clinical evidence of target diseases and symptoms to be treated with Daikenchuto. In this forum, four clinical studies (bowel group, hepatic surgery group, gastrointestinal group, and clinical pharmacology group) and a basic research project, which aimed to elucidate the action mechanism of Daikenchuto, were commenced. The results of these studies were presented in academic congresses in Japan as well as overseas, and all results were published in English-language medical journals in 2015, including the Journal of the American College of Surgeons (JACS). In the field of gastrointestinal surgery today, the concept of the ERAS protocol* is attracting attention in relation to early recovery after surgery.Daikenchuto acts to improve enterokinetics and intestinal blood flow and reduce inflammation, and its efficacy as part of the ERAS protocol is being examined. Currently, investigations are underway in 14 centers in Japan to determine its effectiveness in treating gastrointestinal disorder after liver transplantation in adults. A study on abdominal bloating after laparoscopic-assisted surger has been commenced as this type of surgery helps patients achieve an early recovery and the surgical burden on the human body is less than with conventional surgical methods. ERAS protocol: A post-operative management method to introduce medically proven　approaches that help promote early recovery after surgery in a comprehensive manner.(“ERAS” stands for “enhanced recovery after surgery.”)
Rikkunshito	Target disease and symptoms Epigastrium malaise and loss of appetite in relation to certain diseases such as functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) Overview Rikkunshito was introduced in the “Evidence-based Clinical Practice Guidelines for GERD 2015” (The Japanese Society of Gastroenterology) as a treatment method based on various clinical studies conducted up until that time. The results of the clinical study on ADME for healthy people were published in the July 2015 edition of medical journal PLOS ONE. In addition to efficacy information, safety information is improving as we started our monitoring of adverse drug reaction frequency survey in FY2016. In the field of gastrointestinal medicine, we will utilize the knowledge gained from various past studies and pursue the effectiveness of Kampo products by conducting research on other prescriptions such as Hangeshashinto for patients for whom Rikkunshito does not have sufficient efficacy. In addition, we have started clinical studies to confirm the effectiveness of Kampo products centering on Rikkunshito for loss of appetite in the geriatric field, which is one of three important domains in our new medium-term management plan.
Yokukansan	Target disease and symptoms Behavioral and Psychological Symptoms of Dementia (BPSD)* Overview n FY2004, we began accumulating evidence on Yokukansan, and elucidated the action mechanism. The active components were identified and the absorption of Yokukansan’s components into the blood was confirmed for healthy people. In the clinical field, evidence for the effectiveness and safety of the product is being accumulated by confirmation of its efficacy for Behavioral and Psychological Symptoms of Dementia (BPSD) and through the “monitoring of adverse drug reaction frequency survey.” Yokukansan was introduced into the “Clinical Guidelines for Treatment of Dementia 2010” (Japanese Society of Neurology) and “Guidelines for Safe Drug Therapy for Elderly Patients 2015” (Japan Geriatrics Society), and has become a widely recognized therapy for BPSD. The result of a clinical study on sleep disorder in dementia patients was published in the Journal of Prevention of Alzheimer’s Disease, and it has been broadly applied to diseases with psychoneurotic symptoms including insomnia and anxiety neurosis. Based on research findings to date, we will further pursue the effectiveness of Kampo products by advancing research on other prescriptions for patients for whom Yokukansan does not have sufficient efficacy, as well as studies on the use of Yokukansan and other similar prescriptions in BPSD treatment.
Goshajinkigan Hangeshashinto	Target disease and symptoms Goshajinkigan：Peripheral neuropathy (numbness, etc.) in relation to anti-cancer drugs, etc. Hangeshashinto：Mucosal disorders (diarrhea, mouth ulcer) due to anti-cancer drugs, etc. Overview While Goshajinkigan focuses on peripheral neuropathy (numbness, pain, and cold sense) in relation to anti-cancer drugs, Hangeshashinto works on gastrointestinal mucosal disorders (diarrhea and stomatitis) relating to chemotherapy (administration of anti-cancer drugs) and radiotherapy. We are conducting research on reducing all symptoms. As a result, a research paper titled “HANGESHA-G Study” was published in the May 2015 edition of Cancer Chemotherapy and Pharmacology (CCP), indicating the effectiveness of Hangeshashinto in relation to stomatitis during chemotherapy for the treatment of cancer. To build up a body of evidence in the field of cancer treatment, numerous basic and clinical research projects and GCP* ministerial ordinance-compliant post-marketing clinical studies are being conducted to elucidate the efficacy of Rikkunshito for nausea and loss of appetite, etc. due to the administration of anti-cancer agents. In addition, the effectiveness of Kampo products is being investigated for cancer-related fatigue, for which there are strong needs in the field of cancer treatment. GCP (Good Clinical Practice): A standard establishing criteria for the conduct of clinical studies on pharmaceutical products.