WO2010058280A1 - Composé complexe de métal-salène auto-magnétique - Google Patents

Composé complexe de métal-salène auto-magnétique Download PDF

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Publication number
WO2010058280A1
WO2010058280A1 PCT/IB2009/007525 IB2009007525W WO2010058280A1 WO 2010058280 A1 WO2010058280 A1 WO 2010058280A1 IB 2009007525 W IB2009007525 W IB 2009007525W WO 2010058280 A1 WO2010058280 A1 WO 2010058280A1
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WO
WIPO (PCT)
Prior art keywords
compound
ano
tumor
metabolic
drug
Prior art date
Application number
PCT/IB2009/007525
Other languages
English (en)
Japanese (ja)
Inventor
石川，義弘
江口，晴樹
Original Assignee
株式会社Ihi
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 株式会社Ihi filed Critical 株式会社Ihi
Priority to CN2009801465709A priority Critical patent/CN102239138A/zh
Priority to EP09827243.8A priority patent/EP2357166B1/fr
Priority to JP2010539038A priority patent/JP5513405B2/ja
Priority to RU2011124913/04A priority patent/RU2495045C2/ru
Publication of WO2010058280A1 publication Critical patent/WO2010058280A1/fr
Priority to US13/112,409 priority patent/US9505732B2/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
    • C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/295—Iron group metal 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • 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
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
    • C07C251/24—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to carbon atoms of six-membered aromatic rings

Definitions

  • the present invention relates to a self-body compound having a self property.
  • a drug is administered to a living body and reaches a part, and produces a therapeutic result by producing a result in the local part.
  • the drug reaches the outside (mari), it cannot be treated.
  • drug which induces drugs to the affected area
  • This drag has at least two points. This means that a sufficiently high drug level can be obtained in some tissues. It does not occur unless the drug level in the affected area is constant, and results cannot be expected at low concentrations.
  • the agent can be guided only to the affected tissue to suppress the action of normal tissue.
  • the drug is most effective for cancer caused by anticancer drugs.
  • Most anti-cancer drugs inhibit cancer cell growth that causes cell division, so even normal tissue suppresses growth of cells that cause cell division, such as roots and digestive membranes. To do.
  • cancer patients who have been administered anticancer drugs have effects such as hair loss and vomiting. These side effects are a heavy burden on the patient, so the dosage must be limited, and there is a problem that sufficient anticancer drug results cannot be obtained.
  • oncological drugs the ability to bind aki () to acne tumors, nucleic acid white, etc. is also a generic term for anti-cancer drugs. Inhibits the production of N, resulting in cells. It works on cells in the working phase regardless of the cell stage, and has a strong effect on proliferating cells, and easily damages bone marrow, digestion, reproduction, hair roots, and the like.
  • Biomaterials are substances produced by microorganisms
  • results are shown by directly applying to the minute, which plays an important role in maintaining the function of cells, such as the formation of microscopically during cell division and the transport of substances in cell organs. It affects cells and nerve cells where cell division is active.
  • Platinum preparations also inhibit N formation by forming N or a bond. Splat is a typical agent, but the damage is strong and abundant.
  • molecules are therapeutic methods targeting children that correspond to molecular biological features specific to each sex tumor.
  • topomelase an enzyme that temporarily cuts N and changes the number of N chains.
  • Topoi melase 1 is an enzyme that cuts the strand of the cyclic N, passes the other strand, then closes the cut, and topo melase 1 temporarily cleaves the two of the cyclic N In the meantime, another 2 N is passed between them, and the cut is again a gap.
  • Anti-cancer drugs mostly suppress the growth of cancer cells that cause cell division, so even normal tissues suppress the growth of tissues that cause cell division, such as roots and digestive membranes. I did it. For this reason, cancer patients who have been administered anti-cancer drugs have effects such as hair loss and vomiting.
  • anti-cancer drugs can be induced to cancer cells by dragging and concentrating on the cancer cells to exert their effects, thereby suppressing side effects and effectively treating cancer. It has been done. There is a kind of topic, even locally.
  • Kai product name Kikaine
  • Kai is effective but has arrhythmia.
  • drugs can be used to induce anticancer drugs to cancer cells and concentrate on the cancer cells to exert their results, thereby suppressing side effects and effectively cancer. It has been done.
  • Drugs are also expected to prevent local dispersal and achieve reduced drug efficacy and side effects.
  • the present invention is characterized by the following.
  • the charge dynamics are preferably 5 (e).
  • R is a local intoxicating agent having a self-body compound in which R is a deviation of any of (28) to (38) in which hydrogen is eliminated from a compound having a methyl group and a charge movement of 0 5 (e). is there.
  • R is a compound having any of the following compounds (39) to (03), which is bonded to the case of the compound 1 or 1 by the bond formed by the elimination of hydrogen.
  • a (C) is a bond.
  • This is a sex tumor agent having an autologous compound.
  • G aT is pVa Gy
  • R is a sex tumor having an autologous compound comprising the following (04) to (09) compounds.
  • one of the 8 positions in the following compound 11 is a self-element that imparts sex to the compound when it is bonded to another compound.
  • any one of the 8 positions in the following compound V, and any one of the 96 positions are self-children that bind to other compounds to impart a property to the object.
  • a body for producing a magnetic body comprising the following compounds.
  • Each R is hydrogen, or one is hydrogen and the other is Ox (x is O or ge).
  • 2x of the following compound 11 is a method of a sex form in which a drug molecule is bonded to the position of 5 via an ad group.
  • Sex is obtained in the child structure of one sex compound that is chemically combined with the body containing the drug, and by controlling the field when this child structure is administered to an animal, the drug molecule is controlled. It is possible to provide a sex body that exerts fruit by being guided to the target site and localized in the affected area. A simple description of the surface
  • Fig. 5 is a plan view showing the main points of a state where stones are brought into contact with a frus with a ground of 6 rats.
  • 3 is a graph showing the big of N.
  • Fig. 7 is a graph showing the results of N of a compound in which xeno is bound.
  • Ming has its own pharmacology (for example), and has the property of combining sex with other drugs to impart sex to drugs.
  • the body was made as follows.
  • the compound of po yphospho c ac d (200) was 0 C.
  • the compound was completely dissolved in 500 liters of water. Furthermore, when the 400 h was added, it was separated into the second phase. 44 As a result of removing the aqueous phase and drying the remaining product with an agent 2 and anhydrous, a COOD 2 of 7 (57) was formed.
  • n was z (ES S) 322 4 (eo 7mu) H nN0 eq esm z32 23 was z (ES M 3184 eo 0 m) and H4 N0 eq esm z 318 29.
  • I entered from Tokyo Narita (T 0318 CS 4167 8) o
  • o sa en In comparison with Fe sa en, o sa en has a lot of magnetization on the field of 100000e (T (Tesla)). n sa en has more magnetization on 300000e (3T (Tesla)) than Fe sa en.
  • Fe sa en is suitable for a drug system that uses a large amount of iron even under 00000e (T (Tesla)).
  • T (Tesla) the formation of the field o sa en n sa en in a magnetic field above 10 e T (Tesla) is the most suitable for a drug stem that uses conductive stone.
  • Fig. 5 shows the contact of a rat with 6 rat follicles.
  • Fig. 6 shows the result of calculating the number of cells after photographing from the end of the lath surface after 48 hours.
  • the magnets indicate the area opposite to the lath surface. As shown in Fig. 6, it can be seen that n bodies are attracted from the magnet, and the body is increased, and the cells are extremely low than far away for the production of the body. As a result, the stem provided with the magnetic agent and the magnetic generation stage according to the present invention can concentrate the agent on the affected area or tissue targeted by the individual.
  • a guidance device In this guide device, as shown in FIG. 7, a pair of 230s facing each other are supported by a stud 234 club 235, and a metal 236 is placed between magnets.
  • a metal especially a steel plate, as a pair, a uniform and strong field can be created locally.
  • This induction device can change the generated force by using electromagnets instead of stones.
  • the force generation stage can be moved to the target position of the solid on the table. By placing a solid weave in this area, the drug can be concentrated in this weave. Place the mouse on the board so that the right kidney is between the pair of stones.
  • Figure 9 shows the results of the body against the length in us. No was formed to n V vo in Us by the planting of No (Kun 3 No).
  • the body was applied from the tail vein (50 g kg), and a local field was prepared using commercially available (63 T, cylindrical iridium, length 50, diameter 2 O). Immediately after putting the stone body into 0-4, it was done by bringing the nocite into contact with 3 or.
  • the stone was run for a long period of time between 2 and 0 below the mouse so that the maximum magnetic field was expected at the site where the length was expected. After the insertion of the body, the length of the cell was evaluated by evaluating the region of the cell.
  • the degree of 10C was increased from 2C (2). This is
  • N 3 indicates N big
  • 4 indicates N big
  • 5 indicates big
  • 6 indicates big. Because n,, and are sex bodies, the spin number detected by N is symbiotic with the electron spin number that appears for magnetic bodies.
  • the magnetic material is 3 ⁇ 442 p, 3 ⁇ 03 gpp, 2 ⁇ 4 5 pp, 2 ⁇ 6 pp, 3 ⁇ 14 gppn, Fe is 2 ⁇ 52 2 pp and 3 ⁇ 347 pm, and 2 pp is confirmed. On the other hand, if it is not a magnetic material, there is no peak at 2pp.
  • compound 3 e (di) d ca bona e) was liquefied and allowed to stand overnight. After reacting by vaporizing in the air, the adhered oil was dropped with methano and Na H solution was added. Washed away. Then, compound 5 was obtained by making a raw clay using a lizard as a raw material.
  • Fig. 7 shows N results.
  • Fig. 8 shows the results of mass spectrometry.
  • the compound 5 was poured into a chea (EH) stream while heating, and a thiazia solution was added. The mixture was again flushed 0.5. And when the collected items were collected with a filter, yellow As a result, 6 was obtained.
  • implementation 8 is the same.
  • Rat 6 In the medium, inoculate the medium with a chemical () and (eb oz) compound that can be attracted to woodwork 4 ⁇ 7 (T) conduction (Kugnet). After 48 hours, I photographed the state of the earth.
  • the system comprising the magnetic agent and the magnetic generation stage according to the present invention makes it possible to concentrate the drug on the affected area or tissue targeted by the individual.
  • the amount of the compound bound to (e b oz) was sprinkled on the medium so that it could be attracted to wood craft 4/7 () conduction (Kutto net), and the state of the ground was photographed after 48 hours.
  • the system that realizes this function is provided with a doer source as a pin, that is, a memo, a computing device having a path such as a PU, and a display stage for outputting a computation result.
  • Memo is equipped with a software program that realizes data and data that identifies existing mechanical compounds or structures.
  • the region of the spin degree described is calculated, and the spin degree as a structure is effective.
  • this program for example, commercially available (, access) can be used. 60
  • the user enters the position to add to the compound, selects or changes or deletes, and uses the other program to determine where the bridge is formed. specify.
  • the arithmetic unit calculates the speed and outputs the result to the display surface.
  • the arithmetic unit calculates the speed and outputs the result to the display surface.
  • the flower composition to be combined 033 Add 33 Cyclo 3 32 32 33 and 33033 Huaran. 33 28 Mustine 028 Phosphorus Ramustinium 030 ⁇ 3f Mustine 31 ⁇ 39 Xel 39 ⁇ ccNristine 038 3 Nblastine 0 ⁇ 38 ⁇ 23 Sin 2 33 Levin 33 ⁇ 29 Pin Sin 29 5 Saliplatin 025 2 Carpoplatin 22

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Anesthesiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Rheumatology (AREA)
  • Diabetes (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un médicament doté des propriétés magnétiques d'un complexe de métal-salène représenté par la formule générale en vue de magnétiser un médicament souhaité par liaison chimique du médicament à un complexe de métal-salène afin que le médicament puisse être administré à un site malade cible. L'invention est caractérisée en ce que le médicament est administré à un site malade grâce aux propriétés magnétiques du médicament en tant que tel sans utiliser un véhicule comprenant une matière magnétique comme dans les procédés classiques.
PCT/IB2009/007525 2008-11-20 2009-11-20 Composé complexe de métal-salène auto-magnétique WO2010058280A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CN2009801465709A CN102239138A (zh) 2008-11-20 2009-11-20 自磁性金属salen络合物
EP09827243.8A EP2357166B1 (fr) 2008-11-20 2009-11-20 Composé complexe de métal-salène auto-magnétique
JP2010539038A JP5513405B2 (ja) 2008-11-20 2009-11-20 自己磁性金属サレン錯体化合物
RU2011124913/04A RU2495045C2 (ru) 2008-11-20 2009-11-20 Комплексное соединение самонамагничивающегося металла с саленом
US13/112,409 US9505732B2 (en) 2008-11-20 2011-05-20 Auto magnetic metal salen complex compound

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP2008-297065 2008-11-20
JP2008297065 2008-11-20
JP2008-299482 2008-11-25
JP2008299482 2008-11-25
JP2009177112 2009-07-29
JP2009-177112 2009-07-29

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/112,409 Continuation US9505732B2 (en) 2008-11-20 2011-05-20 Auto magnetic metal salen complex compound

Publications (1)

Publication Number Publication Date
WO2010058280A1 true WO2010058280A1 (fr) 2010-05-27

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Family Applications (1)

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PCT/IB2009/007525 WO2010058280A1 (fr) 2008-11-20 2009-11-20 Composé complexe de métal-salène auto-magnétique

Country Status (6)

Country Link
US (1) US9505732B2 (fr)
EP (1) EP2357166B1 (fr)
JP (1) JP5513405B2 (fr)
CN (2) CN102239138A (fr)
RU (1) RU2495045C2 (fr)
WO (1) WO2010058280A1 (fr)

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WO2011135784A1 (fr) 2010-04-28 2011-11-03 株式会社Ihi Médicament traitant les tumeurs cérébrales
WO2012086683A1 (fr) 2010-12-21 2012-06-28 株式会社Ihi Composé complexe métal-salen et son procédé de production
WO2012111380A1 (fr) * 2011-02-15 2012-08-23 株式会社Ihi Composé de type complexe métal-salen automagnétique
JP2012176905A (ja) * 2011-02-25 2012-09-13 Ihi Corp 金属サレン錯体化合物
WO2012172892A1 (fr) * 2011-06-13 2012-12-20 株式会社Ihi Composé complexe métal salène, anesthésique local, et agent tumoral anti-malignité
WO2013008510A1 (fr) 2011-07-11 2013-01-17 株式会社Ihi Matériau destiné à un condensateur électrique à double couche
WO2013014997A1 (fr) 2011-07-26 2013-01-31 株式会社Ihi Composé complexe métal-salen auto-magnétique
CN102918118A (zh) * 2010-06-01 2013-02-06 株式会社Ihi 荧光色素材料及其使用方法
WO2013051389A1 (fr) 2011-10-04 2013-04-11 株式会社Ihi Agent médicinal sensible à un composé complexe métal-salen, et système pour réguler le comportement in vivo d'un composé complexe métal-salen
WO2013051363A1 (fr) * 2011-10-06 2013-04-11 株式会社Ihi Composition magnétique et procédé de production associé
WO2013061724A1 (fr) 2011-10-27 2013-05-02 株式会社Ihi Inhibiteur de radicaux
US20140039126A1 (en) * 2011-02-05 2014-02-06 Bridgestone Corporation Lanthanide Complex Catalyst And Polymerization Method Employing Same
JP2014058493A (ja) * 2012-09-18 2014-04-03 Hiroshi Kashihara 強磁性を有する核酸の合成方法と利用方法
WO2014092188A1 (fr) 2012-12-14 2014-06-19 株式会社Ihi Corps magnétique et procédé de fabrication d'un corps magnétique
WO2014123115A1 (fr) 2013-02-05 2014-08-14 株式会社Ihi Substance magnétique
JP2014210742A (ja) * 2013-04-19 2014-11-13 株式会社Ihi 持続性磁性抗がん剤
CN104559944A (zh) * 2014-12-24 2015-04-29 西安交通大学 一种含稀土氢氧化物的磁制冷材料及制备方法
JP2015143197A (ja) * 2014-01-31 2015-08-06 株式会社Ihi 新規な金属サレン錯体化合物
WO2016046989A1 (fr) * 2014-09-26 2016-03-31 株式会社Ihi Agent anticancéreux et procédé de destruction de cellules cancéreuses
JP2017128552A (ja) * 2016-01-22 2017-07-27 株式会社Ihi 抗癌剤、抗癌剤の制御方法
JP2017128553A (ja) * 2016-01-22 2017-07-27 株式会社Ihi 抗癌剤、抗癌剤の制御方法
WO2018003587A1 (fr) * 2016-06-27 2018-01-04 株式会社クラレ Procédé de production d'un complexe de fer et procédé de production d'un composé d'ester à l'aide d'un complexe de fer

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US20090169484A1 (en) * 2007-12-28 2009-07-02 Ihi Corporation Iron-salen complex
WO2015146294A1 (fr) * 2014-03-28 2015-10-01 国立大学法人九州大学 Réaction de transestérification effectuée au moyen d'un catalyseur à base de fer
CN107417708B (zh) * 2017-08-04 2019-04-09 广西师范大学 一种水溶性铜(ii)配合物及其合成方法和应用
CN109954516B (zh) * 2017-12-14 2021-12-21 中国科学院大连化学物理研究所 一种用于手性反式第一菊酸制备的Salen/Ru催化剂

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