[go: up one dir, main page]

KR102490334B1 - 암 치료용 아젤니디핀 약학 조성물의 새로운 적응증 - Google Patents

암 치료용 아젤니디핀 약학 조성물의 새로운 적응증 Download PDF

Info

Publication number
KR102490334B1
KR102490334B1 KR1020177011094A KR20177011094A KR102490334B1 KR 102490334 B1 KR102490334 B1 KR 102490334B1 KR 1020177011094 A KR1020177011094 A KR 1020177011094A KR 20177011094 A KR20177011094 A KR 20177011094A KR 102490334 B1 KR102490334 B1 KR 102490334B1
Authority
KR
South Korea
Prior art keywords
cancer
azelnidipine
pharmaceutical composition
cells
inhibition test
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.)
Active
Application number
KR1020177011094A
Other languages
English (en)
Other versions
KR20170084034A (ko
Inventor
츄-훙 천
쇼-메이 촹
쫑-더 웨이
나이-완 샤오
Original Assignee
라운크스 바이오메디컬 컴퍼니 리미티드
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=55760314&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=KR102490334(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by 라운크스 바이오메디컬 컴퍼니 리미티드 filed Critical 라운크스 바이오메디컬 컴퍼니 리미티드
Publication of KR20170084034A publication Critical patent/KR20170084034A/ko
Application granted granted Critical
Publication of KR102490334B1 publication Critical patent/KR102490334B1/ko
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

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
    • A61K31/435—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
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • 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
    • A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • 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
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
    • C07C211/27—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring having amino groups linked to the six-membered aromatic ring by saturated carbon chains
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
    • C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Emergency Medicine (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)

Abstract

본 발명은 아젤니디핀(Azelnidipine)의 새로운 적응증에 관한 것이다. 아젤니디핀은 이미 FDA로부터 승인되었다. 본 발명은 다양한 암세포를 효과적으로 치료하기 위한 아젤니디핀 약학 조성물을 제공한다.

Description

암 치료용 아젤니디핀 약학 조성물의 새로운 적응증{NEW INDICATION OF AZELNIDIPINE PHARMACEUTICAL COMPOSITION FOR TREATING CANCER}
본 발명은 아젤니디핀(Azelnidipine) 약학 조성물의 새로운 적응증에 관한 것으로, 특히 다양한 암 세포에 대한 아젤니디핀 약학 조성물의 억제 효과에 관한 것이다.
아젤니디핀은 고혈압 치료제로서, 단독으로 또는 다른 항고혈압제와 조합하여 사용될 수 있다. 아젤니디핀은 FDA로부터 승인되었고, 약의 용도 및 약리기전 조사에 대한 방대한 자료가 축적되어 있다.
임상적 용도의 차이로 인해, 현재까지 아젤니디핀의 암세포 억제 가능성에 대해 제시하고 있는 연구는 없다.
한편 암은 세계에서 사망의 원인이 되는 가장 대중적인 질병이다. 암 환자는 매년 점차적으로 증가하므로 암 치료 방법이 중요한 문제로 대두되고 있다. 의학적 암 치료는 외과적 치료, 방사선 치료, 화학 요법 및 표적 치료로 분류할 수 있다. 일반적으로 항암제는 화학 요법 약물이든 표적 치료제이든 상관없이 암 세포의 복제를 억제하여 종양의 성장과 전이를 방지한다. 평균적으로, 약 10,000분의 5개의 신약만이 성공적으로 임상 시험 Ⅰ 단계에 진입할 수 있다. 또한, 암 환자가 약물 내성을 일으킨다면, 이는 약물의 효과를 감소시키고 치료 실패를 초래할 수 있다. 따라서 신약 개발은 매우 어렵다.
그러므로, 항암제를 신속하게 개발하고 다양한 암 치료에 대한 임상적 실패 가능성을 줄이는 방법을 강구하는 것은 매우 시급하고 중요한 문제이다.
상술한 문제점을 해결하기 위하여, 본 발명은 아젤니디핀의 새로운 암 임상 적응증의 개발에 대해 제공한다.
따라서, 본 발명은 아젤니디핀의 새로운 적응증을 제공한다. 본 발명의 실험 결과는 아젤니디핀이 정상세포에 대해 독성이 없거나 독성이 거의 없음을 보여주었다. 그러나 정상 세포와 암세포 사이의 아젤니디핀의 선택적 효과는 확인될 필요가 있다.
본 발명은 암 치료를 위한 아젤니디핀의 약학 조성물을 제공한다. 상기 약학 조성물은 유효 투여량의 아젤니디핀 및 약학적으로 허용 가능한 염으로 구성된다.
본 발명의 일 실시예에서, 상기 암은 흉막-관련 암, 복부-관련 암, 내분비계-관련 암, 위장관-관련 암으로부터 선택된다.
본 발명의 일 실시예에서, 상기 암은 골육종, 피부암 및 혈액암으로부터 선택된다.
본 발명의 일 실시예에서, 상기 흉막-관련 암은 폐암이다.
본 발명의 일 실시예에서, 상기 복부-관련 암은 방광암, 자궁경부암으로부터 선택된다.
본 발명의 일 실시예에서, 상기 내분비계-관련 암은 전립선암, 유방암 및 난소암으로부터 선택된다.
본 발명의 일 실시예에서, 위장관-관련 암은 위암, 간암, 결장직장암, 췌장암 및 설암으로부터 선택된다.
본 발명의 일 실시예에서, 아젤니디핀의 유효 투여량은 20 mg/kg/day 내지 500 mg/kg/day 이다.
도1은 각기 다른 암세포에 아젤니디핀이 미치는 억제 효과 결과를 보여준다.
도2는 아젤니디핀에 의한 종양 부피의 억제 효과 결과를 보여준다.
도3은 고용량 및 저용량으로 투여된 아젤니디핀을 통한 종양 성장 억제 효과 결과를 보여준다.
세포 배양
암세포주의 각기 다른 종류는 계대배양(subculture)한다. 상기 암세포는 폐암, 위암, 간암, 대장암, 피부암, 자궁경부암, 전립선암, 방광암, 유방암, 백혈병, 췌장암, 난소암, 설암, 골육종 및 신장암을 포함한다. 대조군에서 사용되는 정상 세포들은 신장 세포(HEK293) 및 사람 기관지 상피세포주 BEAS-2B(표1에서 보는 바와 같음)를 포함했다.
암세포주는 각기 다른 특성 때문에 각각 다른 배지에서 배양하였다(표1에서 보는 바와 같음). 세포 수는 계수하여 셀 배양 판/플라스크에서 2×106으로 재접종(reseed)하였다. 그 후, 상기 배지를 10ml의 부피로 첨가하고, 세포를 2일 내지 3일 동안 배양하였다. 그 후, 세포를 96-웰 플레이트(well plate)에 로딩(loading)하기 위해 부유시켰다. 상기 세포 수는 3000이었고, 상기 배지의 부피는 각 웰(well)당 100㎕였다.
Figure 112017060489289-pct00001
세포 생존능력 분석
96-웰 플레이트에서 원 배지를 제거한다. 그런 다음 웰당 10μM의 농도로 100㎕의 상업적으로 입수가능한 약물을 첨가한다. 72시간 후 희석된 WST-1 시약을 100㎕/웰로 웰에 첨가하고, 상기 희석된 WST-1 시약은 9:1 배지 및 WST-1 스톡(stock)시약의 희석액으로부터 수득하였다. 마지막으로, 각 웰의 총 부피는 200㎕/웰 이었다. 96-웰 플레이트를 37 ℃에서 30분 내지 90분 동안 배양한다. ELISA 판독기로 OD450nm에서, 각 암세포의 생존율을 검출하고 계산한다.
다른 암세포주에 대한 아젤니디핀의 효과
흉막-관련 암세포에 대한 아젤니디핀의 억제 효과
흉막-관련 암세포에 대한 아젤니디핀의 억제 시험에서는, 두 가지의 폐암 세포주로 A549 및 H1650가 사용되었다. 아젤니디핀의 억제 시험은 각 세포주에 대해 4번씩 수행되었고, 억제 시험의 평균값을 계산했다. 그 결과를 하기 표에 나타내었다.
Figure 112017060489289-pct00002
복부-관련 암세포주에 대한 아젤니디핀의 억제 효과
복부-관련 암세포에 대한 아젤니디핀의 억제 시험에서는, 방광암 세포주로 TSGH 및 T24(표3)가, 자궁경부암 세포주로 HeLa 및 C-33A(표4)가, 신장암 세포주로 786-0(표5)가 사용되었다. 아젤니디핀의 억제 시험은 각 세포주에 대해 4번씩 수행되었고, 억제 시험의 평균값을 계산했다. 그 결과를 하기 표에 나타내었다.
Figure 112017060489289-pct00003
Figure 112020106367469-pct00022
Figure 112017060489289-pct00005
내분비계-관련 암세포주에 대한 아젤니디핀의 억제 효과
내분비계-관련 암세포에 대한 아젤니디핀의 억제 시험에서는, 전립선암 세포주로 PC-3(표6)이, 유방암주로 MCF7 및 MDA-MB-231(표7)이, 난소암 세포주로 NIH-OVCAR-3 및 TOV-21G(표8)가 사용되었다. 아젤니디핀의 억제 시험은 각 세포주에 대해 4번씩 수행되었고, 억제 시험의 평균값을 계산했다. 그 결과를 하기 표에 나타내었다.
Figure 112017060489289-pct00006
Figure 112017060489289-pct00007
Figure 112017060489289-pct00008
위장관-관련 암세포주에 대한 아젤니디핀의 억제 효과
위장관-관련 암세포에 대한 아젤니디핀의 억제 시험에서는, 위암 세포주로 AGS 및 MKN-45(표9)가, 간암 세포주로 HepG2 및 Hep3B(표10)가, 결장직장암 세포주로 HCT116-wt 및 LoVo(표11)가, 췌장암 세포주로 AsPC-1 및 BxPC-3(표12)이, 설암 세포주로 SAS(표13)가 사용되었다. 아젤니디핀의 억제 시험은 각 세포주에 대해 4번씩 수행되었고, 억제 시험의 평균값을 계산했다. 그 결과를 하기 표에 나타내었다.
Figure 112017060489289-pct00009
Figure 112017060489289-pct00010
Figure 112017060489289-pct00011
Figure 112017060489289-pct00012
Figure 112017060489289-pct00013
그 외의 다른 암세포주에 대한 아젤니디핀의 억제 효과
그 외의 다른 암세포에 대한 아젤니디핀의 억제 시험에서는, 골육종 세포주로 U2OS(표14)가, 피부암 세포주로 A375 및 BCC(표15)가 사용되었다. 아젤니디핀의 억제 시험은 각 세포주에 대해 3번 내지 4번씩 수행되었고, 억제 시험의 평균값을 계산했다. 그 결과를 하기 표에 나타내었다.
Figure 112017060489289-pct00014
Figure 112017060489289-pct00015
대조군에 대한 실험 설계
정상 세포에 대한 아젤니디핀의 억제 효과
정상 세포에 대한 아젤니디핀의 억제 시험에서는, 정상 신장 세포주로 HEK293(표16)이, 정상 폐 상피세포주로 BEAS-2B(표17)가 사용되었다. 아젤니디핀의 억제 시험은 각 세포주에 대해 4번씩 수행되었고, 억제 시험의 평균값을 계산했다. 그 결과를 하기 표에 나타내었다.
Figure 112017060489289-pct00016
Figure 112017060489289-pct00017
모든 종류의 세포에 대한 아젤니디핀의 억제 시험 결과를 표 18에 나타내었다. 아젤니디핀이 여러 암 세포주에 유의미한 억제 효과를 갖는다는 것은 명백하다. 본 발명의 실험 결과와 같다. 파록세틴(Paroxetine)은 다양한 암세포에 유의미한 억제 효과를 갖는다 (도1).
Figure 112017060489289-pct00018
투여량 100 mg /kg/day 및 200 mg /kg/ day 의 난소암 동물 모델 시험
본 발명에서, 암컷 생쥐(BALB/cAnN.Cg-Foxn1nu/CrlNarl)는 국립 실험 동물 센터(대만)로부터 구입하였다. 생쥐의 무게는 21±1g이었다. 이 생쥐에게 위암 세포(AGS)를 피하 주사한 다음, 생쥐를 무작위로 다른 케이지(cage)에 넣었다. 약물 검사 실험은 "정상 대조군", "저용량 군(100mg/kg/day)"및 "고용량 군(200mg/kg/day)"으로 세 그룹으로 나누었다. 이 생쥐에게 종양 크기가 100mm3에 도달할 때까지 1일 1회 복강 내로 시험 약물을 주입했다. 종양 크기와 체중을 일주일에 두 번 측정했다. 종양 크기는 다음 식에 의해 측정하고 계산했다 : (L×W2). L은 종양의 최장 길이를 나타낸다. W는 종양의 최단 직경을 나타낸다. 실험 결과를 표 19에 나타냈다.
Figure 112017060489289-pct00019
Figure 112017060489289-pct00020
도2의 결과에 따르면, 저용량 및 고용량의 아젤니디핀은 종양 세포에 유의미한 억제 효과를 나타냈다. 반면, 실험 중 생쥐의 무게는 유의미한 감소를 보이지 않았다. 이 결과는 아젤니디핀을 고용량 및 저용량으로 투여한 경우, 실험 생쥐를 치료하는 동안 죽지 않고 건강한 상태로 유지할 수 있음을 나타냈다.
도3의 결과에 따르면, 저용량 및 고용량의 아젤니디핀은 종양 부피 성장을 효과적으로 늦추고, 또한 종양 부피를 감소시킬 수 있다. 특히 고용량의 CellCept는 종양 성장 억제 효과가 더 컸다.
본 발명은 특정 예시적인 실시예 및 예시와 관련하여 기재되어 있더라도, 본 명세서에 개시된 실시예는 단지 예시적 목적을 위한 것이며, 본 기술 분야의 당업자는 하기 청구범위에 기재된 본 발명의 사상 및 범위를 벗어나지 않고 다양한 수정 및 변형을 행할 수 있다는 것을 이해할 것이다.

Claims (8)

  1. 치료적 유효량의 아젤니디핀(Azelnidipine) 또는 이의 약학적으로 허용 가능한 염을 포함하는 암 치료용 약학 조성물로서,
    상기 암은 비소세포 폐암, 난소암(ovarian cancer), 췌장암(pancreatic cancer), 설암(tongue cancer) 및 골육종(osteosarcoma)으로부터 선택되는, 약학 조성물.
  2. 제1항에 있어서,
    상기 아젤니디핀의 유효량은 20mg/kg/day 내지 500mg/kg/day인, 약학 조성물.
  3. 삭제
  4. 삭제
  5. 삭제
  6. 삭제
  7. 삭제
  8. 삭제
KR1020177011094A 2014-10-24 2015-10-23 암 치료용 아젤니디핀 약학 조성물의 새로운 적응증 Active KR102490334B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462068298P 2014-10-24 2014-10-24
US62/068,298 2014-10-24
PCT/CN2015/092714 WO2016062275A1 (zh) 2014-10-24 2015-10-23 阿折地平在制备治疗癌症的医药组合物中的用途

Publications (2)

Publication Number Publication Date
KR20170084034A KR20170084034A (ko) 2017-07-19
KR102490334B1 true KR102490334B1 (ko) 2023-01-18

Family

ID=55760314

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020177011094A Active KR102490334B1 (ko) 2014-10-24 2015-10-23 암 치료용 아젤니디핀 약학 조성물의 새로운 적응증

Country Status (9)

Country Link
US (7) US20170304228A1 (ko)
EP (3) EP3210604B1 (ko)
JP (1) JP6539345B2 (ko)
KR (1) KR102490334B1 (ko)
CN (3) CN107106550A (ko)
AU (2) AU2015335375B2 (ko)
ES (2) ES2954860T3 (ko)
TW (21) TW201615218A (ko)
WO (21) WO2016062275A1 (ko)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RS60205B1 (sr) 2005-12-28 2020-06-30 Vertex Pharma Farmaceutske kompozicije amorfnog oblika n-[2,4-bis(1,1-dimetiletil)-5-hidroksifenil]-1,4-dihidro-4-oksohinolin-3-karboksamida
AU2015335375B2 (en) * 2014-10-24 2020-09-10 Launx Biomedical Co., Ltd. Use of azelnidipine in preparing medicinal composition for treating cancers
EP3236967B1 (en) 2014-12-22 2019-10-16 SUDA Pharmaceuticals Ltd Prevention and treatment of metastatic disease in thrombocytotic cancer patients
WO2017116049A1 (ko) * 2015-12-31 2017-07-06 경북대학교 산학협력단 설폰아마이드계 화합물을 유효성분으로 포함하는 암의 치료 및 전이 억제용 약학적 조성물
EP3241562A1 (en) * 2016-05-02 2017-11-08 Fundació Institut Mar d'Investigacio Medica Zonisamide for use in the treatment of breast cancer
CN106074474A (zh) * 2016-06-15 2016-11-09 中南大学湘雅医院 羟苄丝肼及其在药学上可接受的盐在制备抗肿瘤药物方面的应用
WO2018072135A1 (zh) * 2016-10-19 2018-04-26 微菌方舟生物科技股份有限公司 二氢吡啶类钙拮抗剂用于治疗癌症的用途
CN108066345A (zh) * 2016-11-14 2018-05-25 武汉华杰世纪生物医药有限公司 一种具有抗肿瘤作用的化合物
EP3558276B1 (en) 2016-12-20 2024-11-06 LTS Lohmann Therapie-Systeme AG Transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene
RU2762896C2 (ru) 2016-12-20 2021-12-23 Лтс Ломанн Терапи-Систем Аг Трансдермальная терапевтическая система, содержащая азенапин
US12233073B2 (en) 2017-06-09 2025-02-25 Regents Of The University Of Minnesota Skin care formulations and skin cancer treatment
CN110799180A (zh) 2017-06-26 2020-02-14 罗曼治疗系统股份公司 含阿塞那平和硅氧烷丙烯酸杂化聚合物的经皮治疗系统
EP3648764A4 (en) * 2017-07-03 2021-03-31 Menri Group Ltd. TREATMENT OF CANCER WITH DIHYDROPYRIDINES
JP2019064976A (ja) * 2017-10-03 2019-04-25 国立大学法人 熊本大学 抗がん剤
KR101933805B1 (ko) 2017-10-17 2018-12-28 성균관대학교산학협력단 옥셀라딘시트레이트를 유효성분으로 포함하는 뇌암 예방 또는 치료용 약학적 조성물
CN108186652A (zh) * 2017-12-28 2018-06-22 深圳大学 缝隙连接细胞间通迅抑制剂甘珀酸在制备预防和治疗肝细胞癌药物中的应用
CN111670050A (zh) 2018-01-30 2020-09-15 爱普宁公司(特拉华) 用于治疗睡眠呼吸暂停的方法和组合物
US11931366B2 (en) * 2018-04-19 2024-03-19 Washington University Compositions and methods of use thereof for treatment of proteinopathies
BR112020026099A2 (pt) 2018-06-20 2021-03-23 Lts Lohmann Therapie-Systeme Ag sistema terapêutico transdérmico que contém asenapina
US12329862B2 (en) 2018-06-20 2025-06-17 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system containing asenapine
FR3090084B1 (fr) 2018-12-18 2023-10-13 Securengy Projectile pour armes à feu ou air comprimé pour emport liquide ou pulvérulent.
WO2020132253A1 (en) * 2018-12-19 2020-06-25 University Of Vermont And State Agricultural College Cancer therapeutic compositions and methods
US12285401B2 (en) 2019-04-04 2025-04-29 Daegu-Gyeongbuk Medical Innovation Foundation Pharmaceutical composition comprising trimebutine or pharmaceutically acceptable salt thereof as an active ingredient for prevention or treatment of cancer
WO2020206078A1 (en) * 2019-04-05 2020-10-08 University Of North Texas Health Science Center At Fort Worth Antidepressants for the treatment or prevention of memory loss and/or cognitive decline or dysfunction in aging
EP3953000A4 (en) * 2019-04-11 2023-06-07 Ian Basil Shine CELL MEMBRANE PERMEABILITY RESTORATION THERAPY
CN110179803A (zh) * 2019-05-31 2019-08-30 天津科技大学 一种噻吨溴类化合物的应用
EP3797773A1 (en) * 2019-09-03 2021-03-31 Square Power Ltd Rebamipide for use in prophylaxis and treatment of cancer
CN110742890A (zh) * 2019-10-24 2020-02-04 暨南大学 洛美利嗪在制备抗结肠癌药物中的应用
CN110840887A (zh) * 2019-11-18 2020-02-28 杭州彗搏科技有限公司 三氯苯达唑在制备治疗乳腺癌的药物中的应用
CN110876800B (zh) * 2019-11-18 2023-06-27 中南大学 米卡芬净在制备抗肿瘤药物中的应用及抗肿瘤药物
CN111067899B (zh) * 2020-01-08 2021-03-05 温州医科大学 一种抗疟药物磷酸伯氨喹在制备治疗白血病药物上的应用
US11304969B2 (en) * 2020-01-24 2022-04-19 The Florida International Univeristy Board Of Trustees Treatments of prostate cancer
CN111973593A (zh) * 2020-05-09 2020-11-24 深圳市罗湖区人民医院 硝唑尼特及其药学上可接受的盐在制备治疗膀胱癌药物中的用途
CN111557941A (zh) * 2020-06-15 2020-08-21 浙江大学 Plod2的小分子抑制剂米诺地尔在肿瘤治疗中的应用
CN111848717A (zh) * 2020-08-07 2020-10-30 四川大学 靶向调控线粒体能量代谢的化合物及其应用和药物
WO2022033465A1 (zh) * 2020-08-10 2022-02-17 萧乃文 具有协同抗癌功效的氯硝柳胺和双硫仑医药组合物及其用途
CN112274525B (zh) * 2020-12-04 2022-04-08 遵义医科大学 一种化疗药物组合物及其应用
CN112336725A (zh) * 2020-12-11 2021-02-09 吴照球 甲氧苄啶的医药新用途
CN112569342A (zh) * 2020-12-21 2021-03-30 中南大学 卡泊芬净和/或其可药用盐在制备抗肿瘤药物中的应用及抗肿瘤药物
CN112569215A (zh) * 2020-12-30 2021-03-30 东莞市人民医院 度米芬在制备防治结直肠癌的药物中的应用
EP4108244A1 (en) * 2021-06-25 2022-12-28 Universität Regensburg Ss-lactam antibiotic with significant activity against cancer e.g. colon malignancies
CN113663071B (zh) * 2021-06-28 2022-12-30 四川大学 Fbxl2激活剂在制备治疗egfr驱动的肺癌的药物中的用途
WO2023006954A1 (en) 2021-07-30 2023-02-02 Fundació Institut D'investigació Biomèdica De Bellvitge (Idibell) Asenapine for use in cancer
WO2023035200A1 (zh) * 2021-09-09 2023-03-16 中国福利会国际和平妇幼保健院 五氟利多在制备治疗子宫内膜癌的药物中的应用
CN115887455B (zh) * 2022-08-04 2024-04-05 北京大学人民医院 钙离子通道阻滞剂阿折地平在制备治疗子宫内膜癌的药物中的应用
CN115778957B (zh) * 2022-11-04 2024-06-21 天津中医药大学 千金藤素及包含其的组合物用于预防或治疗酒精性肝病的应用
CN116850266B (zh) * 2023-06-02 2025-05-16 大连医科大学附属第一医院 多粘菌素e甲磺酸钠在制备治疗三阴性乳腺癌药物中的应用
CN116570579A (zh) * 2023-06-13 2023-08-11 深圳市泛谷药业股份有限公司 一种含有阿戈美拉汀和氟伏沙明的药物组合物及其应用
CN116808176B (zh) * 2023-08-30 2023-12-05 上海彗天锦泽生物医学科技有限公司 一种基于免疫检查点阻断的抗肿瘤药物组合物及其应用
US20250213584A1 (en) * 2023-12-27 2025-07-03 Fundação D. Anna De Sommer Champalimaud E Dr. Carlos Montez Champalimaud Ercc1-xpf complex inhibitor compounds and the use thereof in the treatment of cancer
CN118059099B (zh) * 2024-04-19 2024-06-14 四川大学华西医院 帕罗西汀联合asct2抑制剂用于制备治疗肝癌的药物中的应用及药物组合物

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014018563A2 (en) 2012-07-23 2014-01-30 The Board Of Trustees Of The Leland Stanford Junior University Methods for the treatment of cancer
US20140235556A1 (en) * 2011-09-27 2014-08-21 Biomed Valley Discoveries, Inc. Compositions and methods of treating gliomas

Family Cites Families (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ291231B6 (cs) * 1993-10-01 2003-01-15 Syntex (U.S.A.) Inc. Farmaceutický prostředek obsahující mofetil mykofenolát nebo kyselinu mykofenolovou, a způsob jeho přípravy
PT801564E (pt) * 1994-12-28 2002-09-30 Janssen Pharmaceutica Nv Utilizacao de nebivolol como agente anti-aterogernico
CN1149991C (zh) * 1998-09-15 2004-05-19 伊莱利利公司 持久性疼痛的治疗
US6927223B1 (en) * 2000-05-26 2005-08-09 Washington State University Research Foundation Use of serotonin agents for adjunct therapy in the treatment of cancer
BRPI0112269B8 (pt) * 2000-07-07 2021-05-25 Paratek Pharm Innc composto de minociclina 9-aminometila substituída, e, composição farmacêutica
IL139975A0 (en) * 2000-11-29 2002-02-10 Univ Ramot Anti proliferative drugs
US20040072824A1 (en) * 2001-06-01 2004-04-15 Adam Telerman Methods and compositions for the treatment of cancer
GB0202337D0 (en) * 2002-02-01 2002-03-20 Univ Birmingham Cancer treatment
US7135575B2 (en) * 2003-03-03 2006-11-14 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
CA2538570A1 (en) * 2003-09-18 2005-03-31 Combinatorx, Incorporated Combinations of drugs for the treatment of neoplasms
JP2007510670A (ja) * 2003-11-06 2007-04-26 セルジーン・コーポレーション サリドマイドを用いた、癌、及び他の疾患を治療、及び管理する方法ならびに組成物
KR100775549B1 (ko) * 2004-05-12 2007-11-16 주식회사바이오러넥스 나이아신아마이드 또는 그의 유도체를 유효한 성분으로포함하는 암 예방 및 치료제
WO2005112945A2 (en) * 2004-05-21 2005-12-01 The President And Fellows Of Harvard College Synthesis of tetracyclines and analogues thereof
CN1279980C (zh) * 2004-10-14 2006-10-18 孔庆忠 一种抗实体肿瘤药物组合物
JP2006298781A (ja) * 2005-04-15 2006-11-02 Geno Membrane:Kk エストロン３硫酸トランスポーター活性阻害剤
TW200716141A (en) * 2005-05-05 2007-05-01 Combinatorx Inc Compositions and methods for treatment for neoplasms
CN101223149A (zh) * 2005-07-05 2008-07-16 特瓦制药工业有限公司 制备缬沙坦的方法
DK1909778T3 (en) * 2005-07-28 2018-03-19 Academisch Ziekenhuis Bij De Univ Van Amsterdam Monophenol, benzenediol or sulfhydryl compounds for use in the treatment of melanomas
US8148356B2 (en) * 2005-08-24 2012-04-03 Cumberland Pharmaceuticals, Inc. Acetylcysteine composition and uses therefor
AU2007230724B2 (en) * 2006-03-23 2014-01-30 Amgen Inc. Methods and compositions for making and using polymorphs of cinacalcet
CN101099724A (zh) * 2006-07-07 2008-01-09 上海复旦复华药业有限公司 一种微粉化来曲唑及其组合物
CN101103976A (zh) * 2006-07-14 2008-01-16 海南盛科生命科学研究院 一种含阿那曲唑的口服药物组合物及其制备工艺
JP2010515682A (ja) * 2007-01-05 2010-05-13 コーナーストーン セラピューティックス インコーポレイテッド 喘息などの５−リポキシゲナーゼ活性上昇および／またはロイコトリエン活性上昇に関連する状態における使用のためのｒ−ジロートン
CN101730526A (zh) * 2007-03-07 2010-06-09 阿布拉科斯生物科学有限公司 作为抗癌剂的包含雷帕霉素和白蛋白的纳米颗粒
WO2009002427A2 (en) * 2007-06-21 2008-12-31 Amgen Inc. Methods of synthesizing cinacalcet and salts thereof
US20090054312A1 (en) * 2007-08-22 2009-02-26 Wolf Dieter A SMIPs: Small molecule inhibitors of p27 depletion in cancers and other proliferative diseases
US20120082659A1 (en) * 2007-10-02 2012-04-05 Hartmut Land Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations
CN100563645C (zh) * 2007-12-06 2009-12-02 济南帅华医药科技有限公司 一种治疗实体肿瘤的蓓萨罗丁缓释植入剂
US20090270397A1 (en) * 2008-04-08 2009-10-29 Orlow Seth J Methods and compositions for the treatment of cancers, such as melanomas and gliomas
CN101569624A (zh) * 2008-04-29 2009-11-04 石药集团中奇制药技术（石家庄）有限公司 氨氯地平在制备治疗细胞增生性疾病药物中的用途
EP2123626A1 (en) * 2008-05-21 2009-11-25 Laboratorios del Dr. Esteve S.A. Co-crystals of duloxetine and co-crystal formers for the treatment of pain
WO2009147169A1 (en) * 2008-06-03 2009-12-10 Universite Paris Diderot-Paris 7 Pharmaceuticl compositions useful for the treatment of cancers, in particular acute myeloid leukemia and acute promyelocytic leukemia
CN101612400A (zh) * 2009-07-22 2009-12-30 陈志龙 血管紧张素ⅱ的1型受体拮抗剂在抗肿瘤中的应用
CN101690816A (zh) * 2009-08-16 2010-04-07 王丽燕 含钙拮抗剂、aⅱ受体拮抗剂和他汀类药的药物组合物
CN101991553B (zh) * 2009-08-21 2015-02-25 北京以岭生物工程技术有限公司 一种依西美坦片及其制备方法
CN101863806B (zh) * 2010-03-18 2013-02-13 湖北省医药工业研究院有限公司 抗前列腺癌药物(r)-比卡鲁胺的制备方法
WO2011146583A2 (en) * 2010-05-19 2011-11-24 Elan Pharma International Limited Nanoparticulate cinacalcet formulations
WO2012015023A1 (ja) * 2010-07-29 2012-02-02 国立大学法人京都大学 抗がん剤のスクリーニング方法
US20130261142A1 (en) * 2010-12-15 2013-10-03 Hung-Cheng Lai Compounds used for treating cancer and the use thereof
CN102631354B (zh) * 2011-02-11 2015-01-21 广东泰禾医药科技有限公司 含维生素d3和二甲双胍的药物组合物
CN102688493B (zh) * 2011-03-25 2014-09-10 鼎泓国际投资（香港）有限公司 含有白藜芦醇及白藜芦醇类衍生物和Bc1-2抑制剂的药物组合物及其应用
CN102813643B (zh) * 2011-06-10 2014-09-24 北京蛋白质组研究中心 bumetanide在抑制肝癌细胞转移中的应用
AU2012335009B2 (en) * 2011-11-10 2017-08-31 Kai Pharmaceuticals, Inc. Calcimimetics and methods for their use
CN102600077B (zh) * 2012-03-29 2013-06-05 江苏豪森药业股份有限公司 吉西他滨或其盐纳米乳剂注射液及其制备方法
ES2384069B1 (es) * 2012-03-29 2013-07-04 Hospital Sant Joan De Déu Cinacalcet y tumores neuroblásticos
CN103536607A (zh) * 2012-07-10 2014-01-29 邵金辉 土霉素，普罗帕酮和安乃近的抗肿瘤作用
WO2014036654A1 (en) * 2012-09-06 2014-03-13 Mcmaster University Compounds and methods for selectively targeting cancer stem cells
DK2897620T3 (da) * 2012-09-21 2020-08-17 Intensity Therapeutics Inc Fremgangsmåde til behandling af cancer
BR112015007144A2 (pt) * 2012-10-04 2017-12-12 Ab Science uso de masitinib para o tratamento de câncer em subpopulações de paciente identificadas usando fatores prognosticadores
CN103356687B (zh) * 2012-10-19 2016-06-01 厦门大学 一种伊维菌素及其衍生物的用途
AU2014204733B2 (en) * 2013-01-14 2016-09-08 Clinics Operations Limited Cancer drug and uses
CN103933569B (zh) * 2013-01-22 2017-01-11 复旦大学 一种抗肺癌药物组合物及其应用、药盒和包装件
EP2970145B1 (en) * 2013-03-11 2020-05-06 The Broad Institute, Inc. Compounds and compositions for the treatment of cancer
US20140271727A1 (en) * 2013-03-18 2014-09-18 National Yang-Ming University Method of using an antidepressant for increasing immunity of a subject and treating cancer
CN104161759B (zh) * 2013-05-16 2019-10-08 中国科学院上海药物研究所 阿那格雷及其衍生物的抗肿瘤用途
CN103396419A (zh) * 2013-08-13 2013-11-20 海宁市绿升医药科技有限公司 肿瘤光动力治疗药二氢卟吩e6-15-乙酯及其制备方法
CN103536925B (zh) * 2013-10-28 2015-07-01 中国医学科学院基础医学研究所 强心苷化合物在非小细胞肺癌治疗中的应用
CN103622975B (zh) * 2013-11-07 2016-06-15 广东药学院 格列吡嗪在制备治疗肿瘤药物中的应用
JP2017515800A (ja) * 2014-04-08 2017-06-15 ザ・メソジスト・ホスピタル ｉＮＯＳ阻害組成物および乳がん治療薬としてのその使用
AU2015335375B2 (en) * 2014-10-24 2020-09-10 Launx Biomedical Co., Ltd. Use of azelnidipine in preparing medicinal composition for treating cancers

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140235556A1 (en) * 2011-09-27 2014-08-21 Biomed Valley Discoveries, Inc. Compositions and methods of treating gliomas
WO2014018563A2 (en) 2012-07-23 2014-01-30 The Board Of Trustees Of The Leland Stanford Junior University Methods for the treatment of cancer

Also Published As

Publication number Publication date
EP3210604B1 (en) 2024-02-14
EP3235497A1 (en) 2017-10-25
CN106999470A (zh) 2017-08-01
TWI663969B (zh) 2019-07-01
AU2015335391B2 (en) 2018-06-21
TW201615221A (zh) 2016-05-01
WO2016062285A1 (zh) 2016-04-28
TW201615193A (zh) 2016-05-01
TW201615189A (zh) 2016-05-01
TW201615191A (zh) 2016-05-01
WO2016062271A1 (zh) 2016-04-28
AU2015335375B2 (en) 2020-09-10
EP3222278B1 (en) 2023-06-14
KR20170084034A (ko) 2017-07-19
US20170304387A1 (en) 2017-10-26
JP2017532351A (ja) 2017-11-02
WO2016062269A1 (zh) 2016-04-28
US20170304388A1 (en) 2017-10-26
US20170216247A1 (en) 2017-08-03
JP6539345B2 (ja) 2019-07-03
EP3235497A4 (en) 2018-06-13
ES2954860T3 (es) 2023-11-27
EP3222278C0 (en) 2023-06-14
WO2016062287A1 (zh) 2016-04-28
WO2016062288A1 (zh) 2016-04-28
WO2016062283A1 (zh) 2016-04-28
TWI652060B (zh) 2019-03-01
EP3222278A4 (en) 2018-06-20
TW201615218A (zh) 2016-05-01
TW201615195A (zh) 2016-05-01
TWI621434B (zh) 2018-04-21
US10045962B2 (en) 2018-08-14
WO2016062281A1 (zh) 2016-04-28
EP3210604C0 (en) 2024-02-14
TWI663984B (zh) 2019-07-01
TW201615220A (zh) 2016-05-01
US20170304228A1 (en) 2017-10-26
CN107106523A (zh) 2017-08-29
TW201615186A (zh) 2016-05-01
TW201615192A (zh) 2016-05-01
EP3210604A4 (en) 2018-06-27
WO2016062290A1 (zh) 2016-04-28
ES2973279T3 (es) 2024-06-19
WO2016062265A1 (zh) 2016-04-28
TW201615196A (zh) 2016-05-01
TW201615219A (zh) 2016-05-01
TW201615217A (zh) 2016-05-01
US10098852B2 (en) 2018-10-16
WO2016062267A1 (zh) 2016-04-28
TW201615225A (zh) 2016-05-01
TW201615223A (zh) 2016-05-01
WO2016062272A1 (zh) 2016-04-28
TWI672150B (zh) 2019-09-21
TW201615222A (zh) 2016-05-01
WO2016062291A1 (zh) 2016-04-28
WO2016062279A1 (zh) 2016-04-28
EP3210604A1 (en) 2017-08-30
WO2016062274A1 (zh) 2016-04-28
TW201615197A (zh) 2016-05-01
TW201615194A (zh) 2016-05-01
US20170312260A1 (en) 2017-11-02
US20170304218A1 (en) 2017-10-26
TW201615184A (zh) 2016-05-01
AU2015335375A1 (en) 2017-05-18
TW201615188A (zh) 2016-05-01
WO2016062275A1 (zh) 2016-04-28
WO2016062277A1 (zh) 2016-04-28
WO2016062270A1 (zh) 2016-04-28
TW201615226A (zh) 2016-05-01
US10105357B2 (en) 2018-10-23
TW201615224A (zh) 2016-05-01
AU2015335391A1 (en) 2017-06-01
WO2016062286A1 (zh) 2016-04-28
CN107106550A (zh) 2017-08-29
WO2016062278A1 (zh) 2016-04-28
EP3222278A1 (en) 2017-09-27
WO2016062266A1 (zh) 2016-04-28
WO2016062289A1 (zh) 2016-04-28
US20170304286A1 (en) 2017-10-26

Similar Documents

Publication Publication Date Title
KR102490334B1 (ko) 암 치료용 아젤니디핀 약학 조성물의 새로운 적응증
CN106822128A (zh) 酪氨酸激酶抑制剂dcc‑2036的新应用
WO2015178426A1 (ja) がん幹細胞の増殖抑制剤
Zhang et al. Evodiamine inhibits ESCC by inducing M-phase cell-cycle arrest via CUL4A/p53/p21 axis and activating noxa-dependent intrinsic and DR4-dependent extrinsic apoptosis
TW202034919A (zh) 西奧羅尼用於小細胞肺癌的治療
CN112263578B (zh) Tipranavir在制备杀伤肿瘤干细胞和肿瘤细胞的癌症治疗药物中的用途
CN107625756B (zh) 1,6-己二醇或其衍生物在制备抗肿瘤药物中的应用
Azmi et al. P-76 Genomic and transcriptomic characterization of pancreatic neuroendocrine tumors reveals novel therapeutic candidates
CN110721183A (zh) Met和axl双靶点抑制剂在制备防治胃癌的药物中的用途
Ostanin Stimulation of endogenous stem cells in controlled eosinophilic syndrome against cancer

Legal Events

Date Code Title Description
PA0105 International application

Patent event date: 20170424

Patent event code: PA01051R01D

Comment text: International Patent Application

PG1501 Laying open of application
PA0201 Request for examination

Patent event code: PA02012R01D

Patent event date: 20201008

Comment text: Request for Examination of Application

E902 Notification of reason for refusal
PE0902 Notice of grounds for rejection

Comment text: Notification of reason for refusal

Patent event date: 20220622

Patent event code: PE09021S01D

E701 Decision to grant or registration of patent right
PE0701 Decision of registration

Patent event code: PE07011S01D

Comment text: Decision to Grant Registration

Patent event date: 20221205

GRNT Written decision to grant
PR0701 Registration of establishment

Comment text: Registration of Establishment

Patent event date: 20230116

Patent event code: PR07011E01D

PR1002 Payment of registration fee

Payment date: 20230116

End annual number: 3

Start annual number: 1

PG1601 Publication of registration