CN110290802A - [6r]-mthf-在基于5-氟尿嘧啶的化学疗法中的有效叶酸替代物 - Google Patents

[6r]-mthf-在基于5-氟尿嘧啶的化学疗法中的有效叶酸替代物 Download PDF

Info

Publication number
CN110290802A
CN110290802A CN201880008885.6A CN201880008885A CN110290802A CN 110290802 A CN110290802 A CN 110290802A CN 201880008885 A CN201880008885 A CN 201880008885A CN 110290802 A CN110290802 A CN 110290802A
Authority
CN
China
Prior art keywords
cancer
bolus
day
minutes
weeks
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201880008885.6A
Other languages
English (en)
Chinese (zh)
Inventor
皮尔·伦纳特·林德伯格
冈内尔·伊丽莎白·桑德
本特·古斯塔夫森
安德斯·韦丁
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Isofol Medical AB
Original Assignee
Isofol Medical AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Isofol Medical AB filed Critical Isofol Medical AB
Publication of CN110290802A publication Critical patent/CN110290802A/zh
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
CN201880008885.6A 2017-08-24 2018-01-05 [6r]-mthf-在基于5-氟尿嘧啶的化学疗法中的有效叶酸替代物 Pending CN110290802A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP17187684.0A EP3446704A1 (en) 2017-08-24 2017-08-24 [6r]-mthf - an efficient folate alternative in 5-fluorouracil based chemotherapy
EP17187684.0 2017-08-24
PCT/EP2018/050273 WO2019037898A1 (en) 2017-08-24 2018-01-05 [6R] -MTHF - EFFECTIVE ALTERNATIVE TO FOLATE IN CHEMOTHERAPY BASED ON 5-FLUOROURACILE

Publications (1)

Publication Number Publication Date
CN110290802A true CN110290802A (zh) 2019-09-27

Family

ID=59702573

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201880008885.6A Pending CN110290802A (zh) 2017-08-24 2018-01-05 [6r]-mthf-在基于5-氟尿嘧啶的化学疗法中的有效叶酸替代物

Country Status (19)

Country Link
US (2) US11013744B2 (enExample)
EP (3) EP3446704A1 (enExample)
JP (2) JP7356411B2 (enExample)
KR (1) KR102216031B1 (enExample)
CN (1) CN110290802A (enExample)
AU (1) AU2018320069B2 (enExample)
BR (1) BR112020003585A2 (enExample)
CA (2) CA3073555C (enExample)
DK (1) DK3446705T3 (enExample)
ES (1) ES2901621T3 (enExample)
HU (1) HUE057332T2 (enExample)
IL (1) IL272874B2 (enExample)
MX (1) MX2020002053A (enExample)
PL (1) PL3446705T3 (enExample)
PT (1) PT3446705T (enExample)
RU (1) RU2763934C2 (enExample)
SG (2) SG11202001372TA (enExample)
TW (1) TWI752147B (enExample)
WO (1) WO2019037898A1 (enExample)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3446704A1 (en) 2017-08-24 2019-02-27 Isofol Medical AB [6r]-mthf - an efficient folate alternative in 5-fluorouracil based chemotherapy
US20240350495A1 (en) * 2023-04-20 2024-10-24 Isofol Medical Ab [6r]-mthf in b6 enhanced 5-fu based chemotherapy of carcinoma
EP4450071A1 (en) 2023-04-20 2024-10-23 Isofol Medical AB [6r]-mthf in b6 enhanced 5-fu based chemotherapy of pancreatic cancer
US20240350467A1 (en) * 2023-04-20 2024-10-24 Isofol Medical Ab [6r]-mthf in b6 enhanced 5-fu based chemotherapy of pancreatic cancer
EP4534088A1 (en) 2023-10-04 2025-04-09 Isofol Medical AB Arfolitixorin for use in vitamin b6-enhanced, 5-fluorouracil-based chemotherapy of carcinomas

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1942189A (zh) * 2004-04-02 2007-04-04 阿德文特克斯药物有限公司 5,10－亚甲基四氢叶酸在癌症治疗中的用途
CN104114173A (zh) * 2012-01-20 2014-10-22 伊索弗尔医药公司 四氢叶酸酯/盐与egfr抑制剂的组合
CN105452250A (zh) * 2013-08-14 2016-03-30 默克及其合伙人公司 5,10-亚甲基-(6r)-四氢叶酸的半硫酸盐

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5376658A (en) 1990-05-11 1994-12-27 University Of Southern California 5,10-methylene-tetrahydrofolate as a modulator of a chemotherapeutic agent
US7135575B2 (en) 2003-03-03 2006-11-14 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
JP2007531728A (ja) * 2004-04-02 2007-11-08 アドベントルクス ファーマシューティカルズ， インコーポレイテッド 癌の処置のための５，１０−メチレンテトラヒドロ葉酸の使用
KR20070019725A (ko) 2004-04-02 2007-02-15 어드벤트륵스 파마슈티칼스, 인크. 암치료에 사용되는 5,10-메틸렌 테트라하이드로폴레이트의용도
WO2005117876A1 (en) 2004-06-01 2005-12-15 University Of Virginia Patent Foundation Dual small molecule inhibitors of cancer and angiogenesis
WO2007064968A2 (en) * 2005-12-02 2007-06-07 Adventrx Pharmaceuticals, Inc. Stable pharmaceutical compositions of 5,10 methylenetetrahydrofolate
CA2663599A1 (en) 2006-09-18 2008-03-27 Boehringer Ingelheim International Gmbh Method for treating cancer harboring egfr mutations
WO2008109349A1 (en) 2007-03-06 2008-09-12 Adventrx Pharmaceuticals, Inc. Improved regimen for treating cancer with 5-fluorouracil, 5,10-methylenetetrahydrofolate and capecitabine
EP2173875B1 (en) 2007-06-15 2017-08-30 Cequent Pharmaceuticals, Inc. Bacteria mediated gene silencing
RU2482496C2 (ru) 2008-09-26 2013-05-20 Эститю Де Кансероложи Де Л'Вест Оптимизация индивидуальных доз 5-фторурацила при режиме folfox
CA2796205A1 (en) 2010-04-15 2011-10-20 Vegenics Pty Limited Combination treatment with vegf-c antagonists
EP2617422A1 (en) 2012-01-20 2013-07-24 Isofol Medical AB Anti-tumor activity of reduced folates like methylene-tetrahydrofolate, tetrahydrofolate or methyl-tetrahydrofolate
RU2728571C2 (ru) 2015-07-27 2020-07-30 Инносимаб Пте Лтд Лечение пациентов с диагнозом аденокарцинома протоков поджелудочной железы с использованием моноклональных антител к рецептору эпидермального фактора роста (egfr)
EP3446703A1 (en) 2017-08-24 2019-02-27 Isofol Medical AB 6r]-mthf multiple bolus administration in 5-fluorouracil based chemotherapy
EP3305318A1 (en) 2016-10-05 2018-04-11 Isofol Medical AB [6r]-5,10-methylenetetrahydrofolate in 5-fluorouracil based chemotherapy
EP3446704A1 (en) 2017-08-24 2019-02-27 Isofol Medical AB [6r]-mthf - an efficient folate alternative in 5-fluorouracil based chemotherapy
WO2018150264A1 (en) 2017-02-14 2018-08-23 Isofol Medical Ab METHODS FOR INCREASING BLOOD PLASMA 2'-DEOXYURIDINE (dUrd) AND THYMIDYLATE SYNTHASE INHIBITION
US20230116137A1 (en) * 2017-08-24 2023-04-13 Isofol Medical Ab Methods for treating colorectal and metastatic colorectal cancers
MX2020007009A (es) 2018-01-05 2020-11-11 Isofol Medical Ab Metodos para tratar canceres colorrectales metastasicos y colorrectales.
CN113286589A (zh) 2018-05-30 2021-08-20 大卫·马舒瓦尔 用于治疗癌症的方法和药物组合物
WO2023046304A1 (en) 2021-09-27 2023-03-30 Isofol Medical Ab [6r]-mthf in 5-fu based chemotherapy of braf- or kras-mutated colorectal cancer
WO2023046307A1 (en) 2021-09-27 2023-03-30 Isofol Medical Ab [6r]-mthf in 5-fu based chemotherapy of right-sided colorectal cancer
WO2023046305A1 (en) * 2021-09-27 2023-03-30 Isofol Medical Ab [6r]-mthf in 5-fu based chemotherapy of left-sided colorectal cancer
US20230095428A1 (en) * 2021-09-28 2023-03-30 Isofol Medical Ab [6r]-mthf in 5-fu based chemotherapy of braf- or kras-mutated colorectal cancer
US20230097085A1 (en) 2021-09-28 2023-03-30 Isofol Medical Ab [6r]-mthf in 5-fu based chemotherapy of right-sided colorectal cancer
US20240350495A1 (en) 2023-04-20 2024-10-24 Isofol Medical Ab [6r]-mthf in b6 enhanced 5-fu based chemotherapy of carcinoma
US20240350467A1 (en) 2023-04-20 2024-10-24 Isofol Medical Ab [6r]-mthf in b6 enhanced 5-fu based chemotherapy of pancreatic cancer

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1942189A (zh) * 2004-04-02 2007-04-04 阿德文特克斯药物有限公司 5,10－亚甲基四氢叶酸在癌症治疗中的用途
CN104114173A (zh) * 2012-01-20 2014-10-22 伊索弗尔医药公司 四氢叶酸酯/盐与egfr抑制剂的组合
CN105452250A (zh) * 2013-08-14 2016-03-30 默克及其合伙人公司 5,10-亚甲基-(6r)-四氢叶酸的半硫酸盐

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MUHAMMAD WASIFSAIF等: "Phase III Multicenter Randomized Clinical Trial to Evaluate the Safety and Efficacy of CoFactor?/5-Fluorouracil/Bevacizumab Versus Leucovorin/5-Fluorouracil/Bevacizumab as Initial Treatment for Metastatic Colorectal Carcinoma", 《CLINICAL COLORECTAL CANCER》 *

Also Published As

Publication number Publication date
WO2019037898A1 (en) 2019-02-28
EP3446705B1 (en) 2021-09-22
CA3073555A1 (en) 2019-02-28
HUE057332T2 (hu) 2022-05-28
EP3446705A1 (en) 2019-02-27
CA3073555C (en) 2023-01-10
MX2020002053A (es) 2020-12-11
KR20190022270A (ko) 2019-03-06
JP2019038797A (ja) 2019-03-14
SG11202001372TA (en) 2020-03-30
PL3446705T3 (pl) 2022-05-23
AU2018320069B2 (en) 2024-11-21
US20210401842A1 (en) 2021-12-30
JP7356411B2 (ja) 2023-10-04
SG10201800195XA (en) 2019-03-28
US12527796B2 (en) 2026-01-20
EP3446704A1 (en) 2019-02-27
KR102216031B1 (ko) 2021-02-16
RU2763934C2 (ru) 2022-01-11
AU2018320069A1 (en) 2020-03-05
EP3672623A1 (en) 2020-07-01
CA2991357A1 (en) 2019-02-24
RU2020109130A3 (enExample) 2021-09-24
IL272874A (en) 2020-04-30
JP2020531490A (ja) 2020-11-05
ES2901621T3 (es) 2022-03-23
TWI752147B (zh) 2022-01-11
IL272874B1 (en) 2023-12-01
RU2020109130A (ru) 2021-09-24
PT3446705T (pt) 2021-12-29
TW201912159A (zh) 2019-04-01
IL272874B2 (en) 2024-04-01
US20190060316A1 (en) 2019-02-28
US11013744B2 (en) 2021-05-25
BR112020003585A2 (pt) 2020-09-01
DK3446705T3 (da) 2021-12-13

Similar Documents

Publication Publication Date Title
TWI772354B (zh) 在基於5-氟尿嘧啶的化療中[6r]-亞甲基四氫葉酸的多次推注施用
US12527796B2 (en) [6R]-MTHF—an efficient folate alternative in 5-fluorouracil based chemotherapy
EP3305318A1 (en) [6r]-5,10-methylenetetrahydrofolate in 5-fluorouracil based chemotherapy
WO2018065445A1 (en) [6r]-mthf multiple bolus administration in 5-fluorouracil based chemotherapy
WO2018065446A1 (en) [6r]-mthf - an efficient folate alternative in 5-fluorouracil based chemotherapy
HK40047408A (en) [6r]-mthf multiple bolus administration in 5-fluorouracil based chemotherapy

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination