Kotobuki pharmaceutical Co., Ltd.

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Company History;

Starting with “Apricots”

dozo1

Timeline list

【Phase 1】 Establishment of Pharmaceutical Companies Based on Regional Resources (1949–1959)
“Beginning with the production of crude drugs based on regional resources, they laid the foundation as pharmaceutical companies.”
1949

・Misao Tomiyama, a representative employee and partner of Kotobuki Shokai, a limited partnership established in 1931, receives a license from Nagano Prefecture to manufacture and sell pharmaceuticals at the company’s Toyono Plant in Nagano City and establishes Kotobuki Seiyakusho.
The limited partnership, Kotobuki Shokai, had produced apricot jam, and produced apricot kernel water from apricot seeds, which were mostly waste.
By cultivating herbal medicines in Nagano Prefecture, the company will also contribute to the preservation of the natural environment and the creation of job opportunities in Nagano Prefecture.
These initiatives align with the principles of today’s SDGs.
kyoninsui_color（オリジナル）
Apricot kernel water : AQUA ARMENIACAE “KOTOBUKI”

・The company joins the Nagano Pharmaceutical Association (located in the Nagano Pharmaceutical Hall) under the trade name Kotobuki Seiyaku Co.and begins business activities.

1950
・Kotobuki Seiyakujo is moved from Toyono, Nagano City to 6343 Sakaki, Sakaki Town, and the production of Apricot kernel water.
1951

・Kotobuki Pharmaceutical Co., Ltd. is registered as a corporation (capital of 300,000 yen).

・Misao Tomiyama took office as president.

・Joined Nagano Crude Drug Promotion Committee.

・Became the initiator of the establishment of the “Sakaki Medicinal plants Association”.

Company nameplate at the time of establishment

・Begins production of “Lotus Extract” and “Senega Syrup”.

Lotus extract: EXTRACTUM SCOPOLIAE “KOTOBUKI”
1952
・Professor Michikazu Fujita of the Faculty of Pharmaceutical Sciences at the University of Tokyo submitted an article to the Journal of Pharmacognosy, stating that the content of saponin in senega root cultivated in our company was superior to that of expensive senega root imported from North America.
1956
・Export rutin to Europe and America.
1959
・10th anniversary of foundation.

・Awarded as an excellent workplace by the Minister of Labor during National Labor Hygiene Week.

・Moved the head office to 6352, Sakaki, Sakaki-machi.
【Phase 2】Industrialization of Pharmaceutical Manufacturing through Chemically Synthesized Drugs (1960s–1970s)
“Achieving industrialization of pharmaceutical manufacturing through the shift to chemically synthesized drugs”
1960

・Moved the head office to 6351, Sakaki, Sakaki-machi.

・【Transformation of business from crude drugs to synthetic chemical pharmaceuticals.】A new “API plant with reinforced slate roof” will be built adjacent to the head office and the crude drug formulation plant for the production of chemically synthesized drugs.

　Exterior view of API plant

・Opened Osaka Office.

1962

・Begins production and sales of “Buformin Hydrochloride” for the first time as a chemically synthesized drug.
1965_hanbai

1964
・Begins production and marketing of “Triamterene“.
1967

・Begins production and marketing of ”Clofibrate”, the first domestically produced ”Clofibrate”.

Clofibrate production facilities

・Begins production and marketing of protoporphyrin disodium and exports to Taiwan, South Korea and other overseas markets.

・Launched Gastritis, Gastric ulcer, duodenal ulcer therapeutic agent MARZULENE-S GRANULES in Japan.
(Activate drug discovery research on azulenes of Japanese origin)

Advertisement at the time of release

・QVF reactor introduced.

1968
・Begins production and marketing of ADETIDE ENTERIC COATED TAB and DIBETON S TAB (ENTERIC COATED), the first enteric-coated formulations produced in Japan.
1969
・20th anniversary of foundation.
1971
・Moved the head office factory to 198, Higashigawara, Kamigomyo, Sakaki-machi.
【Transformation of the External Environment: Internationalization of Medicinal Resources】
1972
・With the normalization of diplomatic relations between Japan and China, direct imports of inexpensive Chinese crude drugs began, and Japanese cultivation of medicinal plants suffered a major blow and declined rapidly. Chinese crude drugs eventually came to account for about 80% of the domestic market.

・This shift significantly altered the structure of Japan’s crude drug industry, which had relied on domestic medicinal herbs, and became the backdrop for companies shifting their focus toward chemically synthesized pharmaceuticals and research and development.
1973
・Opened Tokyo office.
1976
・Introduced high-speed 3-way filling and packaging machine.
1978
・Completion of pharmacy plant based on GMP (Good Manufacturing Practice).

Completion of the first stage construction of Research Laboratory.
　
1979
・30th anniversary of foundation.

Panoramic view of the head office
【Phase 3】Transition to a Research-Based Pharmaceutical Company (1980s–1990s)
“Transition to a research-based company through laboratory development and international academic presentations”
1981
・Through a Cabinet announcement, the new and old fonts “Kotobuki Pharmaceutical Co., Ltd.” and “Trademark Registration No. 6086766” came to be widely used.
1982
・Tsuyoshi Tomiyama took office as president.
1983

・Completion of the second stage construction of Research Laboratory.

・Introduced high-speed automatic continuous packaging machine and continuous granulation dryer.

1984
・Study abroad system.

・MARZULENE S COMBINATION GRANULES ranked No. 1 in terms of sales by brand of medicinal products.
1985
・The results of synthesis and pharmacological studies of a new compound, Azuloxa (eguarene), are presented for the first time at the Pharmaceutical Society of Japan.
1986
・We presented our results for the first time at the The Federation of American Societies for Experimental Biology (FASEB) Meeting.
1987

・Completion of research facilities of Radio Isotope.

・Held “Kotobuki Symposium” at the Japan-America Joint Pharmaceutical Meeting in Hawaii.
1988

・Our research paper published for the first time in Chemical & Pharmaceutical Bulletin.

・The results of synthesis and pharmacological studies of “2H-cyclohepta[b]furan-2-one” are presented for the first time at the Chemical Society of Japan.
1989

・Founding 40th anniversary commemorative magazine “Housu” published.

・Our research paper published for the first time in Journal of Medicinal Chemistry.

・Kotobuki Pharmaceutical was selected as one of the referees for submitted papers in the American Chemical Society’s Journal of Medicinal Chemistry.
1990
・Launched Gastritis, Gastric ulcer, duodenal ulcer therapeutic agent MARZULENE-S GRANULES in China.
麦滋林（中国）
1992

・Additional set of drug substance manufacturing equipment in the south area of the second drug substance factory.

・Present the results of synthesis and pharmacological testing of a new compound for the first time at the American Chemical Society (ACS).
1993

・Completion of the second pharmacy plant based on GMP.

・Research paper published for the first time in Bioorganic & Medicinal Chemistry Letters, a journal of the Elsevier’s.

・Kotobuki Pharmaceutical was selected as one of the referees for submitted papers in Elsevier’s “Bioorganic & Medicinal Chemistry Letters.”

1996
・Completion of API 4th factory.
1999
・50th anniversary of foundation.
【Phase 4】Evolution into a Knowledge-Intensive Drug Discovery Company (2000s Onward)
“Evolving into a knowledge-intensive drug discovery company through proprietary drug discovery and international collaborative research”
2000

・Launched Gastritis, Gastric ulcer, duodenal ulcer therapeutic agent MARZULENE-S GRANULES in India.

2001

・Launched new Gastric ulcer therapeutic agent AZULOXA GRANULES (Egualen Sodium) in Japan.

・Introduced external lubricant spray device.

2003

・Launched Gastritis, Gastric ulcer, duodenal ulcer therapeutic agent MARZULENE ES TABLETS (Dosage form addition) in Japan.

2004
・Conformed to the inspection for compliance with the GCP (Good Clinical Practice)carried out by PMDA (Pharmaceuticals and Medical Devices Agency).

・Launched Gastric ulcer therapeutic agent AZULOXA GRANULES in South Korea.
アズロキサ顆粒（韓国）
2005
・Conformed to the inspection on synthesized drug substances carried out by foreign country regulatory authority.
2006
・Conformed to the inspection on AZULOXA GRANULES for compliance with the GPMSP (Good Post-Marketing Surveillance Practice) carried out by PMDA.
2007
・Akira Tomiyama took office as president.
2008

・Launched Gastritis, Gastric ulcer, duodenal ulcer therapeutic agent MARZULENE COMBINATION TABLETS 0.5ES (Dosage form addition) in Japan.

・AZULOXA GRANULES 2.5% efficacy expanded to “combination with H2 receptor antagonist”.

2009

・60th anniversary of foundation.

・Launched Gastritis, Gastric ulcer, duodenal ulcer therapeutic agent MARZULENE COMBINATION TABLETS 0.375ES (Dosage form addition) in Japan.

・Co-marketing of AZULOXA GRANULES 2.5%, a gastric ulcer treatment, with Ajinomoto Co., Inc.

2010
・We performed an invitation lecture of cholesterol absorption inhibitor KT6-971 by a medicinal chemistry sectional meeting of Americanization society(ACS).
2011

・We performed an invitation lecture of cholesterol absorption repressor KT6-971 of the new development product in CHINESE ACADEMY SCIENCES.

・Gastric ulcer therapeutic agent AZULOXA TABLETS 15mg in Japan.

・Released “Karate Tablet” in Japan, which is easy to crack with fingers and has high division accuracy.
2012_karate1　2012_karate2

2012

・Joint development Agreement of Cholesterol absorption inhibitor, KT6-971,with Shionogi & Co.,Ltd.

・Co-marketing of “MARZULENE S GRANULES”, “MARZULEN COMBINATION TABLETS 1.0ES”, “0.5ES”, “0.375ES”, “AZULOXA GRANULES 2.5%” and “AZULOXA TABLETS 15mg” for gastritis and peptic ulcer treatment, with Ajinomoto Co., Inc.

2013
・Submits Application for Marketing Approval of Ipragliflozin / Suglat Tablets 25mg, 50mg.
SGLT2 Inhibitor for Treatment of Type 2 Diabetes(Joint development with Astellas Pharma Inc.), in Japan.
2014
・Hiroshi Tomiyama took office as president.

Selective SGLT2 Inhibitor “Suglat Tablets 25mg, 50mg (Suglat, Ipragliflozin L-Proline)”
・Obtained manufacturing and marketing approval in Japan.

・The drug price is listed and published.cameraicon
スーグラ錠25mg、50mg

2015
・President Tomiyama and chief Noda at drug research institute were awarded at 33rd Medicinal Chemistry Symposium by the Pharmaceutical Society of Japan. The title is “Creation of Selective SGLT2 inhibitor –novel oral hypoglycemic agent SuguraTM.

Selective SGLT2 Inhibitor “Suglat Tablets 25mg, 50mg (Suglat, Ipragliflozin L-Proline)”
・Acquires production sale approval in Korea and is published medicine charge. It released it.
・President Hiroshi Tomiyama gave an invited lecture on “Drug Discovery of Sugra Tablet” at Seoul National University in Korea.

FLT3 Inhibitor “XOSPATA 40mg Tablets (XOSPATA, Gilteritinib)”
・We Initiate Phase 3 Registration Trial of gilteritinib (ASP2215) in Relapsed or Refractory Acute Myeloid Leukemia Patients.
・ASP2215 (gilteritinib) was presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).
2016
・Co-marketing of “MARZULENE S GRANULES”, “MARZULEN COMBINATION TABLETS 1.0ES”, “0.5ES”, “0.375ES”, “AZULOXA GRANULES 2.5%” and “AZULOXA TABLETS 15mg” for gastritis and peptic ulcer treatment, with EA Pharma Co.,Ltd.
2017
・The 50th Anniversary Celebration Party for Manufacturing and Marketing Approval of MARZULENE-S GRANULES was held.

Drug combining selective DPP-4 inhibitor and selective SGLT2 inhibitor “SUJANU Combination Tablets (SUJANU, Sitagliptin phosphate hydrate, Ipragliflozin L-Proline)”
・Submits application for approval of type-2 diabetes drug combining selective SGLT2 inhibitor “Suglat Tablets” and selective DPP-4 inhibitor “JANUVIA Tablets”. (Joint development with Astellas Pharma Inc. and MSD)

FLT3 Inhibitor “XOSPATA 40mg Tablets (XOSPATA, Gilteritinib)”
・In July 2017, we obtained “Orphan Drug Designation” from the FDA (US Food and Drug Administration).
・In October 2017, we obtained “Fast Track designation” from the FDA (US Food and Drug Administration).
2018
・MARZULENE-S (China name: 麦滋林TM) for the treatment of gastritis and ulcer exported to China has been certified as an international reference product and original imported product from China National Food and Drug Administration Supervision and Administration Administration (CFDA).

Selective SGLT2 Inhibitor “Suglat Tablets 25mg, 50mg (Suglat, Ipragliflozin L-Proline)”
・Application for additional indication/effect of type 1 diabetes in Japan.
・Acquired approval for additional indications and additional dosage and administration of type 1 diabetes in Japan.

Drug combining selective DPP-4 inhibitor and selective SGLT2 inhibitor “SUJANU Combination Tablets (SUJANU, Sitagliptin phosphate hydrate, Ipragliflozin L-Proline)”

・Approved for manufacturing and sales in Japan, and the drug price is listed and released.
SUJANU_PTP_kaisya enkaku


FLT3 Inhibitor “XOSPATA 40mg Tablets (XOSPATA, Gilteritinib)”
・In January 2018, we obtained “Orphan Drug Designation” from EC (European Commission).
・In March 2018, we obtained “Orphan Drug Designation” from the Ministry of Health, Labor and Welfare.
・In March 2018, we applied for manufacturing and marketing approval in Japan as a treatment for FLT3 gene mutation-positive acute myelogenous leukemia.
・U.S. FDA Grants Priority Review to New Drug Application for Gilteritinib for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia. (AML)
・Announces Approval in Japan for the Treatment of FLT3mut+ Relapsed or Refractory AML.
・Approved by U.S. FDA for Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) with a FLT3 Mutation.
・Launch in Japan. –Provides a new therapeutic option for patients with AML–
・Launch in the U.S. for the Treatment of Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) with a FLT3 Mutation.
2019
・70th anniversary of foundation.
・We have renewed our corporate logo to celebrate our 70th anniversary.
・With the discontinuation of sales of Codeine Powder (Codeine Phosphate Powder 1% “Kotobuki”), which had been on the market since 1963, all herbal medicine preparations were discontinued. This marked the end of all herbal medicine formulation operations that had continued since the company’s founding.
Selective SGLT2 Inhibitor “Suglat Tablets 25mg, 50mg (Suglat, Ipragliflozin L-Proline)”
・Acquires production sale approval in Russia and is published medicine charge. It released it.
FLT3 Inhibitor “XOSPATA 40mg Tablets (XOSPATA, Gilteritinib)”
・Announces Acceptance for Regulatory Review by the European Medicines Agency.
・Phase 3 ADMIRAL Trial Data Show XOSPATA® (gilteritinib) Significantly Prolongs Overall Survival in Adult Patients with FLT3 Mutation-Positive Relapsed/Refractory Acute Myeloid Leukemia　–Study results will be presented at AACR2019–
・U.S. FDA Approves Supplemental New Drug Application Adding Overall Survival Data. –The only FDA-approved targeted treatment for adult patients with relapsed or refractory FLT3 mutation-positive Acute Myeloid Leukemia–
・Receives Positive CHMP Opinion as a Monotherapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation.
・European Commission Approves as a Monotherapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation.
・New England Journal of Medicine Publishes Results from Phase 3 ADMIRAL Trial in Adult Patients with FLT3 Mutation-Positive Relapsed/Refractory Acute Myeloid Leukemia.
・Released in Canada.
2020
FLT3 Inhibitor “XOSPATA 40mg Tablets (XOSPATA, Gilteritinib)”
・Released in Taiwan/Korea/Brazil/Australia.
・Acceptance for Regulatory Review in China by the National Medical Products Administration.
2021
FLT3 Inhibitor “XOSPATA 40mg Tablets (XOSPATA, Gilteritinib)”
・Receives Conditional Approval by China’s National Medical Products Administration for Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation
・Meets Overall Survival Endpoint in COMMODORE Trial of Patients with Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation
・Released in China/Singapore.
2022

・Relocation of Tokyo Office.

・Research on Kawara OD Tablets®, which uses our unique formulation technology, was selected for the 2021 Nagano Prefecture Pharmacists Association Research Grant 21.

・FY2021 “Nagano Prefecture Pharmacists Association Research Grant 21: Voices of Joy from Award Winners (Representative Director and President Yasushi Tomiyama)” was published in the Nagano Prefecture Pharmaceutical Journal “Rindo”.

・Released Tramadol Hydrochloride OD Tablets 25mg/50mg “KO” in Japan.
This product is our “Kawara OD Tablets®”.
　

2023

・The presentation ceremony for the Minister of Health, Labour and Welfare’s Letters of Appreciation to organizations cooperating in promoting blood donation activities for fiscal year 2023 was held.

2024
・75th anniversary of foundation.

Selective SGLT2 Inhibitor “Suglat Tablets 25mg, 50mg (Suglat, Ipragliflozin L-Proline)”
・Released in 3 countries.

FLT3 Inhibitor “XOSPATA 40mg Tablets (XOSPATA, Gilteritinib)”
・Released in 35 countries worldwide.
2025

・Tramadol Hydrochloride OD Tablets 25mg/50mg “KO” for the Treatment of Cancer and Chronic Pain
Recipient of the Encouragement Award for Invention at Kanto Region Local Commendation for Invention, organized by the Japan Institute of Invention and Innovation (JIII)pdf0
Title of Innovation: Miniaturized Oral Tablet Designed for Water-Free Administration

・We began marketing its own single agent for “MARZULENE S GRANULES”, “MARZULEN COMBINATION TABLETS 1.0ES”, “0.5ES”, “0.375ES”, “AZULOXA GRANULES 2.5%” and “AZULOXA TABLETS 15mg” for gastritis and peptic ulcer treatment.