JP5997189B2 - 鉄サレン錯体 - Google Patents
鉄サレン錯体 Download PDFInfo
- Publication number
- JP5997189B2 JP5997189B2 JP2014006299A JP2014006299A JP5997189B2 JP 5997189 B2 JP5997189 B2 JP 5997189B2 JP 2014006299 A JP2014006299 A JP 2014006299A JP 2014006299 A JP2014006299 A JP 2014006299A JP 5997189 B2 JP5997189 B2 JP 5997189B2
- Authority
- JP
- Japan
- Prior art keywords
- drug
- compound
- salen complex
- affected area
- magnetic field
- 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
Links
- VEUMANXWQDHAJV-UHFFFAOYSA-N 2-[2-[(2-hydroxyphenyl)methylideneamino]ethyliminomethyl]phenol Chemical compound OC1=CC=CC=C1C=NCCN=CC1=CC=CC=C1O VEUMANXWQDHAJV-UHFFFAOYSA-N 0.000 title claims description 17
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 title description 8
- 229910052742 iron Inorganic materials 0.000 title description 4
- 239000003814 drug Substances 0.000 claims description 64
- 150000001875 compounds Chemical class 0.000 claims description 41
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 201000011510 cancer Diseases 0.000 claims description 17
- 238000000015 thermotherapy Methods 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 3
- 206010020843 Hyperthermia Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 230000036031 hyperthermia Effects 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 230000020169 heat generation Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 210000001519 tissue Anatomy 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- 201000001441 melanoma Diseases 0.000 description 14
- 230000005389 magnetism Effects 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000012377 drug delivery Methods 0.000 description 9
- 210000003734 kidney Anatomy 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 108020004459 Small interfering RNA Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 229940125782 compound 2 Drugs 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 4
- 208000010228 Erectile Dysfunction Diseases 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 238000004364 calculation method Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
- 201000001881 impotence Diseases 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000004055 small Interfering RNA Substances 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 3
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000000696 magnetic material Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000005094 computer simulation Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 230000004907 flux Effects 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 2
- 239000004312 hexamethylene tetramine Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229960004011 methenamine Drugs 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000002435 tendon Anatomy 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- -1 Iron (III) Schiff-base Chemical class 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 229910052779 Neodymium Inorganic materials 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 230000005880 cancer cell killing Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- QEFYFXOXNSNQGX-UHFFFAOYSA-N neodymium atom Chemical compound [Nd] QEFYFXOXNSNQGX-UHFFFAOYSA-N 0.000 description 1
- 229910001172 neodymium magnet Inorganic materials 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/547—Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/103—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/12—Macromolecular compounds
- A61K49/122—Macromolecular compounds dimers of complexes or complex-forming compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N2/00—Magnetotherapy
- A61N2/002—Magnetotherapy in combination with another treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/02—Iron compounds
- C07F15/025—Iron compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Radiology & Medical Imaging (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
Description
−H
−CO2Me
−CO(OCH2CH2)nOCH3
−NHR1(R1は水酸基を有する置換基である)
である)
本発明の鉄サレン錯体は、磁性を有するため、特定の化合物を結合させた磁性を有する薬剤を提供することができる。
その結果、従来における、経口投与が困難なこと、担体分子が一般的に巨大であること、あるいは薬剤分子との結合強度、親和性に技術的な問題があることを解決することができ、実用化が容易なドラッグ・デリバリ・システムを実現することが出来る。
本発明の鉄サレン錯体は、前記式(I)〜(V)において、R1は、電荷移動が0.5電子(e)未満であることが好ましい。
本発明の薬剤は、上記の鉄サレン錯体からなる。
本発明の薬剤の使用例としては、薬剤自体が磁性を有するため、個体に投与した後、当該個体に磁界を加えて、薬剤を目的とする組織又は患部に誘導させることができる。
別の使用例としては、個体の組織内又は患部内に磁力発生手段を適用し、薬剤を当該組織又は患部に誘導させることができる。
別の使用例としては、個体の組織内又は患部内に当該個体の体液を供給する血管等の経路の途中に磁力発生手段を配置して、薬剤を下流の組織又は患部に誘導させることができる。
別の使用例としては、R1がローダミン(蛍光色素)である鉄サレン錯体からなる薬剤に、光を照射して発光させ、これを検出することで、薬剤の体内動態を検知することができる。
別の使用例として、薬剤を磁場により患部へ誘導後、交流磁場を薬に印加して、がん細胞周辺の温度をがん細胞殺傷温度へ上昇させ、がん細胞のみを殺すことができる。
本発明の薬剤は、体内に投与した薬剤を、当該薬剤の磁性を利用して所定の患部に誘導する誘導システムであって、個体の表面、組織、又は患部に対して磁場を発生する手段を配置するようにした、薬剤誘導システム、に適用することができる。
本発明の薬剤は、体内に投与した薬剤を、当該薬剤の磁性を利用して所定の患部に誘導する誘導システムであって、個体に対して磁場を発生する手段と、当該磁場を前記個体の目的とする組織又は患部に誘導する手段と、を備える薬剤誘導システム、に適用することができる。
前記磁場を発生する手段は、2つの磁石を対にして当該二つの磁石の間に前記目的とする組織又は患部を置き、当該組織又は患部に磁束を集中させるように構成されてなる、ことが好ましい。
前記目的とする組織又は患部は、MRI又はCTによって同定される、ことが好ましい。
本発明の薬剤は、体内に投与した当該薬剤の磁性又は発光を検出することにより、当該薬剤の体内動態を検知する、磁気検出装置、に適用することができる。
前記薬剤の磁性は、磁気共鳴誘導または発光によって検出することが好ましい。
本発明の薬剤の別の使用例として、がん組織に誘導された本薬剤に電磁波を当てることにより、局所的に温度を上昇させ、がん細胞を特異的に殺傷することができる。
このように、本発明の鉄サレン錯体を用いれば、一つの薬剤で機能診断、MRI診断装置、がん化学療法、がん温熱療法、磁場誘導ドラッグ・デリバリ・システム、に適用することができる。
本発明の薬剤の別の使用例として、薬剤の分子モデルを設定し、当該分子モデルについて数値計算により求めたスピン電荷密度から前記分子モデルが磁性を有するか否かを判定し、磁性を有すると判定した分子モデルに基づいて薬剤を設計する方法、を提供することができる。
上記薬剤を設計する方法において、数値計算により、両端に結合する化合物(R1)の電子の授受が0.5電子(e)未満となるように、薬剤の設計をすることができる。
上記薬剤を設計する方法において、スピン電荷密度分布に基づいて分子モデルの磁性の強度を判定することができる。
鉄サレン錯体の合成を、次のように行った。
得られた化合物は、シリカジェルを使ったフラッシュクロマトグラフィーを2回行うことで、10gのcompound 6(収率58%)が得られた。
得られた化合物を、ジエチルエーテルとパラフィンの溶液中で再結晶化させ高速液化クロマトグラフィーで測定したところ、純度95%以上のcomplex A(鉄サレン錯体)5.7g(収率62%)を得た。
その後、両端に、−NHR1、水素結合を多く有する置換基−CO2Me、−CO(OCH2CH2)nOCH3 又は
鉄サレン錯体の合成を、次のように行った。
その後、両端に−NHR1をアシル化、Et3N等の反応ステップを経て、結合させた。
鉄サレン錯体の合成を、次のように行った。
式(I)〜(IV)の化合物とそれに結合する化合物の電子の移動は第一原理計算で求めることができる。
このコンピュータシミュレーションを実現するシステムは。コンピュータとしての公知のハードウエア資源を備えるものであって、すなわち、メモリと、CPUなどの演算回路を備える演算装置と、演算結果を出力する表示手段を備えている。メモリは、既存の有機化合物または3次元構造を特定するデータと、コンピュータシミュレーションを実現するソフトウエア・プログラムを備えている。このソフトウエアは、各化合物の側鎖を追加・変更・削除し、所定の側鎖間で架橋し、記述のスピン電荷密度の高い領域を計算し、構造全体としてのスピン電荷密度を決定可能なものである。このプログラムとして、例えば、市販品(Dmol3、アクセルリス社)を利用することができる。
ユーザは化合物について、側鎖を追加する位置を入力し、または側鎖を変更し、あるいは削除するものを選択し、さらに、架橋を形成すべき箇所をメモリの支援プログラムを利用して演算装置に指定する。演算装置はこの入力値を受けて、スピン電荷密度を演算してその結果を表示画面に出力する。また、ユーザが既存の化合物の構造データをコンピュータシステムに追加することによって、既知の化合物についてのスピン電荷密度を得ることが出来る。
表1に電荷移動の演算結果を示す。表1においては、鉄サレン錯体(化学式(I))とそのR1部分に結合する電荷移動を示した。マイナスは電子が増加していることを示す。プラスは電子が減っていることを示す。
ラットL6細胞が30%のコンフルエントの状態の時に上記式で示される鉄サレン錯体粉末を磁石に引き寄せられるのが目視できる程度の量を培地にふりかけて48時間後に培地の状態を写真撮影した。
図1はラットL6細胞の培地がある角型フラスコに棒磁石を接触させた状態を示している。次いで、48時間後角型フラスコ底面の一端から他端までを撮影し、細胞数を算出した結果を図2に示す。図2において磁石から近位とは、角型フラスコ底面における磁石端面の投影面積内を示し、磁石から遠位とは、角型フラスコ底面において磁石端面と反対側にある領域を示す。
次に本発明に係る誘導装置の他の例について説明する。この誘導装置は、図3に示すように重力方向に互いに向き合う一対の磁石230,232がスタンド234とクランプ235によって支持されており、磁石の間には金属板236が置かれている。一対の磁石間に金属板、特に鉄板をおくことにより、局所的に一様で強力な磁界を作り出すことができる。
この磁界の領域に固体の組織を置くことにより、この組織に薬剤を集中させることができる。体重約30グラムのマウスに既述の金属錯体(薬剤濃度5mg/ml(15mM))を静注して開腹し、右の腎臓を前記一対の磁石の間に来るようにマウスを鉄板の上に置く。
サレン錯体の初回注入の12日後に、メラノーマ浸潤の大きさを評価することによって、メラノーマの増大を評価した。
Claims (2)
- 下記(I)式、又は、(II)式で示される錯体構造を有するサレン錯体化合物を有効成分として含有し、
前記サレン錯体化合物を適用した患部領域への磁場の適用により当該サレン錯体化合物が発熱することに基づいて前記患部領域に対する温熱治療を可能とする温熱治療用薬剤。
式(I)、(II)において、Xは、−Hである。 - 前記患部領域のがん細胞に前記サレン錯体化合物の発熱を適用可能な請求項1記載の温熱治療用薬剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014006299A JP5997189B2 (ja) | 2007-12-28 | 2014-01-16 | 鉄サレン錯体 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007338928 | 2007-12-28 | ||
JP2007338928 | 2007-12-28 | ||
JP2014006299A JP5997189B2 (ja) | 2007-12-28 | 2014-01-16 | 鉄サレン錯体 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009264213A Division JP5461968B2 (ja) | 2007-12-28 | 2009-11-19 | 鉄サレン錯体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014133743A JP2014133743A (ja) | 2014-07-24 |
JP5997189B2 true JP5997189B2 (ja) | 2016-09-28 |
Family
ID=40798707
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008298128A Active JP4446489B2 (ja) | 2007-12-28 | 2008-11-21 | 鉄サレン錯体 |
JP2009264213A Active JP5461968B2 (ja) | 2007-12-28 | 2009-11-19 | 鉄サレン錯体 |
JP2014006299A Active JP5997189B2 (ja) | 2007-12-28 | 2014-01-16 | 鉄サレン錯体 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008298128A Active JP4446489B2 (ja) | 2007-12-28 | 2008-11-21 | 鉄サレン錯体 |
JP2009264213A Active JP5461968B2 (ja) | 2007-12-28 | 2009-11-19 | 鉄サレン錯体 |
Country Status (2)
Country | Link |
---|---|
US (2) | US20090169484A1 (ja) |
JP (3) | JP4446489B2 (ja) |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2036550A4 (en) | 2006-06-28 | 2009-07-15 | Ihi Corp | MEDICAMENT, DRUG DELIVERY DEVICE, MAGNETIC DETECTOR, AND DRUG DESIGN METHOD |
US20090169484A1 (en) * | 2007-12-28 | 2009-07-02 | Ihi Corporation | Iron-salen complex |
JP5077796B2 (ja) * | 2008-03-10 | 2012-11-21 | 独立行政法人科学技術振興機構 | O、s又はnを含む鎖状アルキル化合物の製造方法 |
JP2009289799A (ja) * | 2008-05-27 | 2009-12-10 | Yoshihiro Ishikawa | スイッチング素子 |
CN102239138A (zh) | 2008-11-20 | 2011-11-09 | 株式会社Ihi | 自磁性金属salen络合物 |
WO2011077750A1 (ja) | 2009-12-25 | 2011-06-30 | 株式会社Ihi | 磁石体及び磁石体を用いたドラッグデリバリー制御装置 |
RU2533567C2 (ru) * | 2010-04-06 | 2014-11-20 | АйЭйчАй КОРПОРЕЙШН | Производные комплекса металл-сален и способ их получения |
CN102933216A (zh) | 2010-04-28 | 2013-02-13 | 株式会社Ihi | 抗脑瘤药物 |
EP2578643B1 (en) | 2010-06-01 | 2019-07-10 | IHI Corporation | Fluorescent dye material and use thereof |
SG192062A1 (en) * | 2010-12-21 | 2013-08-30 | Ihi Corp | Metal-salen complex compound and production method for same |
JP2012131737A (ja) * | 2010-12-21 | 2012-07-12 | Ihi Corp | 金属サレン錯体化合物及びその製造方法 |
JP2012176905A (ja) * | 2011-02-25 | 2012-09-13 | Ihi Corp | 金属サレン錯体化合物 |
JP5873656B2 (ja) * | 2011-06-13 | 2016-03-01 | 株式会社Ihi | 金属サレン錯体化合物、局所麻酔薬剤及び抗悪性腫瘍薬剤 |
JP6017766B2 (ja) * | 2011-07-26 | 2016-11-02 | 株式会社Ihi | 新規な金属サレン錯体化合物の抗がん剤 |
JP5829871B2 (ja) * | 2011-09-16 | 2015-12-09 | 株式会社Ihi | リポソーム薬剤 |
WO2013051363A1 (ja) * | 2011-10-06 | 2013-04-11 | 株式会社Ihi | 磁性組成物及びその製造方法 |
JP6280305B2 (ja) * | 2013-02-05 | 2018-02-14 | 株式会社Ihi | 磁性医薬 |
JP5806356B2 (ja) * | 2014-03-10 | 2015-11-10 | 株式会社Ihi | 鉄サレン錯体、磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 |
WO2015146294A1 (ja) * | 2014-03-28 | 2015-10-01 | 国立大学法人九州大学 | 鉄触媒によるエステル交換反応 |
WO2016046989A1 (ja) | 2014-09-26 | 2016-03-31 | 株式会社Ihi | 抗がん剤、がん細胞殺傷方法 |
CN109415304B (zh) * | 2016-06-27 | 2022-07-22 | 株式会社可乐丽 | 铁络合物的制造方法和使用了铁络合物的酯化合物的制造方法 |
IT202000016255A1 (it) * | 2020-07-06 | 2022-01-06 | Eni Spa | Nuovi complessi metallici con leganti tipo-salen. |
Family Cites Families (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL7304882A (ja) | 1972-04-10 | 1973-10-12 | ||
GB1432563A (en) | 1972-04-10 | 1976-04-22 | Rustenburg Platinum Mines Ltd | Platinum- co-ordination compounds |
US4727068A (en) * | 1985-10-23 | 1988-02-23 | Johnson Matthey, Inc. | Radiosensitization by cobalt and Fe(III) complexes |
US4871716A (en) * | 1986-02-04 | 1989-10-03 | University Of Florida | Magnetically responsive, hydrophilic microspheres for incorporation of therapeutic substances and methods of preparation thereof |
JPS62192383A (ja) | 1986-02-20 | 1987-08-22 | Hidetoshi Tsuchida | ポリテトラアザポルフイン鉄錯体および有機磁性材料 |
DE3618840A1 (de) | 1986-06-04 | 1987-12-10 | Basf Ag | Methanol/luft-brennstoffzellen |
JP3000369B2 (ja) * | 1989-05-16 | 2000-01-17 | 日本酸素株式会社 | 酸素吸収錯体の再生方法及び酸素吸収錯体溶液を用いた酸素の分離方法 |
JPH0523276A (ja) | 1991-07-15 | 1993-02-02 | Tokyo Electric Co Ltd | 電気掃除機 |
JP2930263B2 (ja) | 1991-08-12 | 1999-08-03 | 日本化薬株式会社 | 電子写真用トナー |
JPH05216967A (ja) | 1992-02-03 | 1993-08-27 | Hitachi Ltd | 分子設計支援装置 |
US5403834A (en) | 1992-12-07 | 1995-04-04 | Eukarion, Inc. | Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease |
US5696109A (en) | 1992-12-07 | 1997-12-09 | Eukarion, Inc. | Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease |
DE4301871A1 (de) * | 1993-01-13 | 1994-07-14 | Diagnostikforschung Inst | Neue Mittel zur Diagnose von Gefäßerkrankungen |
WO1994016683A1 (en) | 1993-01-29 | 1994-08-04 | Magnetic Delivered Therapeutics, Inc. | Magnetically responsive composition for carrying biologically active substances and methods of production and use |
US6200547B1 (en) | 1994-01-26 | 2001-03-13 | Ferx Incorporated | Magnetically responsive compositions for carrying biologically active substances and methods of production and use |
JPH07296045A (ja) | 1994-04-27 | 1995-11-10 | Hitachi Ltd | 分子設計支援方法 |
ES2170815T5 (es) | 1994-12-29 | 2012-11-14 | Chugai Seiyaku Kabushiki Kaisha | Uso de un anticuerpo PM-1 o de un anticuerpo MH166 para potenciar el efecto antitumoral de cisplatino o carboplatino |
JP3724051B2 (ja) | 1996-04-25 | 2005-12-07 | 住友化学株式会社 | フェノールの酸化重合用触媒およびフェノールの酸化重合法 |
JP3825501B2 (ja) | 1996-06-10 | 2006-09-27 | 吉郎 岡見 | 微小物質保持担体、その懸濁系、微小物質操作装置及び微小物質位置制御方法 |
JP3662347B2 (ja) | 1996-06-10 | 2005-06-22 | 日鉄鉱業株式会社 | 医療用粉体 |
JP2001501596A (ja) | 1996-08-27 | 2001-02-06 | ユニバーシティ・オブ・ユタ・リサーチ・ファウンデーション | バイオコンジュゲートおよび生物学的活性剤の送達 |
JPH10310796A (ja) | 1997-05-14 | 1998-11-24 | Lion Corp | カビ取り剤組成物 |
JP3030849B2 (ja) | 1997-06-18 | 2000-04-10 | 科学技術振興事業団 | 有機高分子化合物の強磁性を予測する方法 |
JPH11217385A (ja) | 1998-01-30 | 1999-08-10 | Nihon Schering Kk | 含フッ素ポルフィリン錯体およびそれを含有する造影剤 |
JPH11279100A (ja) | 1998-03-25 | 1999-10-12 | Asahi Glass Co Ltd | 光学活性な1−置換−2−プロパノールの製造方法 |
US6087368A (en) | 1998-06-08 | 2000-07-11 | Bristol-Myers Squibb Company | Quinazolinone inhibitors of cGMP phosphodiesterase |
JP2000269013A (ja) | 1999-03-12 | 2000-09-29 | Kanagawa Acad Of Sci & Technol | 分子性磁性体 |
WO2001000702A1 (fr) * | 1999-06-29 | 2001-01-04 | Japan As Represented By Secretary Of Agency Of Industrial Science And Technology | Composition a base de resine et procede de production de cette composition |
TW200400821A (en) | 1999-11-02 | 2004-01-16 | Pfizer | Pharmaceutical composition (II) useful for treating or preventing pulmonary hypertension in a patient |
JP4433118B2 (ja) | 2000-09-12 | 2010-03-17 | 日産化学工業株式会社 | 分子磁性体およびその製造方法 |
US6589948B1 (en) * | 2000-11-28 | 2003-07-08 | Eukarion, Inc. | Cyclic salen-metal compounds: reactive oxygen species scavengers useful as antioxidants in the treatment and prevention of diseases |
JP2002226678A (ja) * | 2000-11-28 | 2002-08-14 | Sumitomo Bakelite Co Ltd | 難燃性エポキシ樹脂組成物およびそれを用いた半導体封止材料並びに半導体装置 |
WO2002071054A1 (en) | 2001-03-02 | 2002-09-12 | Metaphore Pharmaceuticals, Inc. | Chromatography of metal complexes |
GB0125357D0 (en) | 2001-10-22 | 2001-12-12 | Univ Brighton | Improvements relating to catalytic antioxidants |
AU2003224917A1 (en) | 2002-04-11 | 2003-10-27 | Carbomer | Diabetes imaging probes |
JP4357847B2 (ja) | 2003-02-04 | 2009-11-04 | 三菱電機株式会社 | 物質の磁気特性を予測する方法 |
GB0316912D0 (en) | 2003-07-18 | 2003-08-20 | Oxford Instr Superconductivity | Therapeutic treatment |
JP2005154402A (ja) * | 2003-10-29 | 2005-06-16 | Nagoya Industrial Science Research Inst | 金属錯体タンパク質複合体及び酸化触媒 |
US7119065B2 (en) | 2003-10-29 | 2006-10-10 | Nagoya Industrial Science Research Institute | Metal complex-protein composite and oxidation catalyst |
JP4265387B2 (ja) | 2003-11-26 | 2009-05-20 | 株式会社日立製作所 | 時刻誤差算出機能付きクライアントサーバシステム |
US20070134338A1 (en) | 2005-06-08 | 2007-06-14 | Bala Subramaniam | Methods for producing nanoparticulate metal complexes and altering nanoparticle morphology |
JP2007091710A (ja) | 2005-08-31 | 2007-04-12 | Ishikawajima Harima Heavy Ind Co Ltd | 薬、薬の誘導装置、磁気検出装置及び薬の設計方法 |
EP2036550A4 (en) | 2006-06-28 | 2009-07-15 | Ihi Corp | MEDICAMENT, DRUG DELIVERY DEVICE, MAGNETIC DETECTOR, AND DRUG DESIGN METHOD |
JP4774536B2 (ja) | 2006-11-06 | 2011-09-14 | 株式会社Ihi | 磁性材料、磁性材料の誘導装置及び磁性材料の設計方法 |
JP5167481B2 (ja) | 2006-11-07 | 2013-03-21 | 株式会社Ihi | 抗がん薬 |
US20090169484A1 (en) | 2007-12-28 | 2009-07-02 | Ihi Corporation | Iron-salen complex |
CN102239138A (zh) * | 2008-11-20 | 2011-11-09 | 株式会社Ihi | 自磁性金属salen络合物 |
CN102933216A (zh) * | 2010-04-28 | 2013-02-13 | 株式会社Ihi | 抗脑瘤药物 |
EP2578643B1 (en) * | 2010-06-01 | 2019-07-10 | IHI Corporation | Fluorescent dye material and use thereof |
SG192062A1 (en) * | 2010-12-21 | 2013-08-30 | Ihi Corp | Metal-salen complex compound and production method for same |
JP6017766B2 (ja) * | 2011-07-26 | 2016-11-02 | 株式会社Ihi | 新規な金属サレン錯体化合物の抗がん剤 |
JP6046338B2 (ja) * | 2011-10-27 | 2016-12-14 | 株式会社Ihi | ラジカル抑制剤 |
-
2008
- 2008-06-26 US US12/146,624 patent/US20090169484A1/en not_active Abandoned
- 2008-11-21 JP JP2008298128A patent/JP4446489B2/ja active Active
-
2009
- 2009-11-19 JP JP2009264213A patent/JP5461968B2/ja active Active
-
2014
- 2014-01-16 JP JP2014006299A patent/JP5997189B2/ja active Active
-
2016
- 2016-01-08 US US14/990,981 patent/US10034941B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP2014133743A (ja) | 2014-07-24 |
JP4446489B2 (ja) | 2010-04-07 |
US10034941B2 (en) | 2018-07-31 |
US20160193337A1 (en) | 2016-07-07 |
JP2010043125A (ja) | 2010-02-25 |
JP2009173631A (ja) | 2009-08-06 |
JP5461968B2 (ja) | 2014-04-02 |
US20090169484A1 (en) | 2009-07-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5997189B2 (ja) | 鉄サレン錯体 | |
JP2010043125A5 (ja) | ||
EP2357166B1 (en) | Auto magnetic metal salen complex compound | |
US10034851B2 (en) | Metal-salen complex compound, local anesthetic and antineoplastic drug | |
EP2682384A1 (en) | Auto-magnetic metal salen complex compound | |
EP2738157B1 (en) | Auto-magnetic metal salen complex compound | |
JP2009274962A (ja) | 鉄サレン錯体、磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 | |
JP2009196913A (ja) | 磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 | |
JP5325427B2 (ja) | 磁性を有する薬剤 | |
JP5806356B2 (ja) | 鉄サレン錯体、磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 | |
JP2009256232A (ja) | 磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 | |
JP2009256233A (ja) | 磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 | |
JP2013170133A (ja) | 無機化合物、無機化合物を含む薬剤、薬剤の誘導システム、及び磁気検出装置、並びにがん温熱治療法装置 | |
JP5433155B2 (ja) | 磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 | |
JP2010000202A (ja) | 医療用チューブ又は薬剤の誘導システム |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150210 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150413 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150526 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150724 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20151110 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160112 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160426 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160627 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160802 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160825 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5997189 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |