Kotobuki’s History;– Kotobuki pharmaceutical Co., Ltd.

it started from an “Apricot”

Timeline list

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 waste¹⁾.
The company also manufactures and sells medicines derived from crude drugs produced in Nagano Prefecture (Senega syrup, lotus extract, etc.).
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 Prefecture²⁾.
Both 1) and 2) are based on the SDGs.

Apricot kernel water

・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. was registered as a corporation.

・Misao Tomiyama took office as president.

・Joined Nagano Crude Drug Promotion Committee.

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.

1960

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

・Opened Osaka Office.

1965

・Began production and marketing of a synthetic drug, buformin hydrochloride.

・Started production and marketing of triamterene.

・President Tomiyama received the Achievement Medal from Sakaki Town.

1967

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

1968

・President Tomiyama was awarded the Prime Minister’s Commendation.

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

1969

・20th anniversary of foundation.

・President Tomiyama was awarded Minister of Justice commendation.

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

　Advertisement at the time of release

1971

・Moved the head office factory to 198, Higashigawara, Kamigomyo, Sakaki-machi.

1973

・Opened Tokyo office.

1978

・President Tomiyama was awarded the Nagano Prefectural Governor’s Award as a meritorious contributor.

・Completion of pharmacy plant based on GMP (Good Manufacturing Practice).
Completion of the first stage construction of Research Laboratory.

1979

・30th anniversary of foundation.

1982

・Senior Adviser Tomiyama was awarded the Conferment of Decoration.

・Tsuyoshi Tomiyama took office as president.

1983

・Completion of the second stage construction of Research Laboratory.

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.

1990

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

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.

1996

・Completion of API 4th factory.

1999

・50th anniversary of foundation.

・President Tomiyama was awarded the Ministry of Health, Labor and Welfare Award as a meritorious contributor.

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.

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.

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.

2010

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

・That the efficacy and safety of ASP-1941 were validated by the Japanese phase Ⅱb and American Phase IIa was presented at American Diabetes Association.

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

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

・We changed development number of cholesterol absorption inhibitor KT6-971 to S-556971.

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.

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.

FLT3 Inhibitor “XOSPATA 40mg Tablets (XOSPATA, Gilteritinib)”

・We Initiate Phase 3 Registration Trial of gilteritinib (ASP2215) in Relapsed or Refractory Acute Myeloid Leukemia Patients.

2017

・Tsuyoshi Tomiyama, our board member’s advisor, received the Medal with Dark Blue Ribbon.

・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

・Tsuyoshi Tomiyama, our board member’s advisor, received the 2018 Japan Pharmacists Association Merit Award.

・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.

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.

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

・Tsuyoshi Tomiyama, our board member’s advisor, received the Order of the Sacred Treasure in the fall of 3rd year of Reiwa.

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.

・Released “Kawara OD Tablet” in Japan.
　