WO2003067979A1 - Medicaments destines a etre utilises dans la transplantation d'organes - Google Patents

Medicaments destines a etre utilises dans la transplantation d'organes Download PDF

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Publication number
WO2003067979A1
WO2003067979A1 PCT/JP2003/001554 JP0301554W WO03067979A1 WO 2003067979 A1 WO2003067979 A1 WO 2003067979A1 JP 0301554 W JP0301554 W JP 0301554W WO 03067979 A1 WO03067979 A1 WO 03067979A1
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WIPO (PCT)
Prior art keywords
carbon atoms
carbon
alkyl
hydrogen atom
carbons
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PCT/JP2003/001554
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English (en)
Japanese (ja)
Inventor
Toshikazu Yoshikawa
Nobuo Kitamura
Jun Fukumoto
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Mitsubishi Pharma Corporation
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 Mitsubishi Pharma Corporation filed Critical Mitsubishi Pharma Corporation
Priority to JP2003567178A priority Critical patent/JPWO2003067979A1/ja
Priority to AU2003211983A priority patent/AU2003211983A1/en
Publication of WO2003067979A1 publication Critical patent/WO2003067979A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0205—Chemical aspects
    • A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
    • A01N1/0226—Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a preservative of a heart for transplantation, which contains a pyrazolone derivative as an active ingredient, and an agent for suppressing ischemia / reperfusion injury after heart transplantation. It is. Furthermore, the present invention relates to a method of transplanting a heart using a bisazolone derivative as an active ingredient.
  • Transplanted hearts removed from an organ donor (donor) for a heart transplant operation may have blood from minutes to tens of hours before being transplanted to the recipient. It is stored in a state where flow is disrupted and oxygen is not supplied through the bloodstream (ischemic condition).
  • R 1 is a hydrogen atom, an aryl, an alkyl having 1 to 5 carbon atoms, or an alcohol having 3 to 6 carbon atoms.
  • R 2 is hydrogen atom, aryloxy, arylmelcapto, alkyl of 1 to 5 carbon atoms or 1 to 5 carbon atoms.
  • R 3 is a hydrogen atom, an phenol having 1 to 5 carbon atoms, a cycloalkyl having 5 to 7 carbon atoms, a carbon atom having 1 carbon atom, From 3 hydroxyalkyl, benzyl, naphthyl or phenyl, or from 1 to 5 carbon atoms, from 1 to 5 carbon atoms.
  • the pyrazolone derivative represented by the formula (1) has a function of normalizing the brain function for use in medicine (Japanese Patent Publication No. 5-311523), a lipid peroxide. Inhibition of production (Japanese Patent Publication No.
  • Japanese Patent Application Laid-Open No. 9_528801 describes the use of the above-described pyrazolipid inducer at the time of renal transplantation, and thus the renal transplantation after renal transplantation. There is a statement that the obstacles have been significantly reduced. However, only the kidney is used as an organ for transplantation, but there is no description of its effect on the heart, no suggestion or teaching. I don't know.
  • the compound of the above formula (I) has been a cerebral protectant (generic name: edaravone, trade name: radiocut): Mitsubishi Pharma Corporation Pharmaceuticals Co., Ltd.), which is marketed under the trade name of ⁇ Pharma Co., Ltd.).
  • this compound is used as a preservation solution for heart transplantation and ischemia-reperfusion injury after heart transplantation. There have been no reports of its usefulness as a suppressant. Disclosure of the invention
  • the objectives of the present invention are to use a preservative for heart transplantation and a drug useful as an agent for suppressing ischemia / reperfusion injury after cardiac transplantation, and a combination with a conventional preservative solution.
  • a preservative for heart transplantation and a drug useful as an agent for suppressing ischemia / reperfusion injury after cardiac transplantation and a combination with a conventional preservative solution.
  • Is not essential Preservative for organs for transplantation and inhibitor for ischemia-reperfusion injury after organ transplantation The purpose of the present invention is to provide a useful medicine.
  • pyrazolone derivatives which have been known to have a cerebral protective effect
  • Hydrate or a pharmaceutical composition containing a pharmacologically acceptable salt thereof as an active ingredient can be used as a preservative for a heart for transplantation and for post-cardiac transplantation. It has been found that it is useful as an agent for suppressing blood reperfusion injury, and further, it has been found that a transplantation method using the active ingredient is useful. We have completed the Ming.
  • the gist of the present invention is as follows.
  • R 1 is a hydrogen atom, an aryl, an alkyl having 1 to 5 carbon atoms, or an alcohol having a total carbon number of 3 to 6)
  • R 2 represents hydrogen atom, aryloxy, arylmethyl, alkyl of 1 to 5 carbon atoms or 1 to 5 carbon atoms.
  • R 1 and R 2 represent an alkylene having 3 to 5 carbon atoms, and represent a hydroxyalkyl of 3 to 3 carbon atoms.
  • R 3 is a hydrogen atom, an alkyl having 1 to 5 carbon atoms, a cycle alkyl having 5 to 7 carbon atoms, a hydrogen atom having 1 to 5 carbon atoms, and a hydroxyalkyl having 1 to 3 carbon atoms.
  • a preservative for a heart for transplantation comprising a pyrazolone derivative represented by the formula (1) or a physiologically acceptable salt thereof as an active ingredient.
  • the preservative as described above which is characterized as being a preservation solution for a heart for transplantation.
  • R 1 is a hydrogen atom, aryl, an alkyl having 1 to 5 carbon atoms or an alcohol having 3 to 6 carbon atoms.
  • R 2 represents a hydrogen atom
  • ⁇ Li Lumpur O key sheet
  • ⁇ Li Lumpur main Le mosquito flop bets were or
  • ⁇ Le key Le having a carbon number of 1 month ⁇ et 5 Represents one, three, or three hydroxyalkyls
  • R 1 and R 2 together represent an alkylene having 3 to 5 carbon atoms
  • R 3 is a hydrogen atom and an alkyl having 1 to 5 carbon atoms.
  • the agent for suppressing ischemia-reperfusion injury after heart transplantation as described above which is a preparation for intravascular administration.
  • R 1 is a hydrogen atom, aryl, 1 carbon atom, an alkyl of 5 carbons or an alkoxyl gas of 3 carbons to 6 carbons.
  • R 2 represents a hydrogen atom, ⁇ Li Lumpur O key sheet, ⁇ Li Lumpur main Le mosquito flop bets, ⁇ Le key Honoré charcoal element number 1, 4, and 5 or Or 1 to 3 hydroxyalkyls, one of which is represented by R 1 and R 2, which are shared and have 3 to 5 carbon atoms.
  • R 3 is a hydrogen atom, an alkyl having 1 to 5 carbon atoms, a cycloalkyl having 5 to 7 carbon atoms, and a 1 carbon atom.
  • R 1 is a hydrogen atom, aryl, carbon number of 1 to 5 carbon atoms or a total carbon number of 3 to 6 carbon atoms.
  • R 2 is hydrogen atom, aryloxy, arylmethylcap, phenol or alkyl having 1 to 5 carbon atoms.
  • 1 to 3 represent hydroxyalkyl
  • R 1 and R 2 together represent an alkylene having 3 carbon atoms to 5 carbon atoms
  • R 3 represents a hydrogen atom, 1 carbon atom to 5 carbon atoms.
  • R 1 is a hydrogen atom, an aryl, an alkyl having 1 to 5 carbon atoms or an alkoxyl force having 3 to 6 carbon atoms.
  • R 2 represents hydrogen atom, aryloxy, arylalkyl, or an alkyl group having 1 to 5 carbon atoms. Represents one to three hydroxyl groups, and some, R 1 and R 2 are shared and have three to five carbon atoms.
  • R 3 is a hydrogen atom, 1 carbon atom, an alkyl of 5 carbons, 5 carbon atoms, 5 cycloalkyls or holes, 7 carbon atoms of 1 carbon atom, etc.
  • R 1 is a hydrogen atom, an aryl, an alkyl having 1 to 5 carbon atoms, or an alcohol having a total carbon number of 3 to 6)
  • R 2 represents hydrogen atom, aryloxy, arylmelcapto, an alkyl of 1 to 5 carbon atoms, or 1 represents 3 hydroxy radicals, or R 1 and R 2 are commonly used to represent 3 to 5 carbon atoms.
  • R 3 is a hydrogen atom, a carbon atom
  • the aryl group in the definition of R 1 in the pyrazopine derivative represented by the above formula (I) is a monocyclic group or a monocyclic group. May be any of the polycyclic aryl groups. For example, phenyl, naphthinole, etc., alkyl, methyl, butyl, etc., alkyl, methoxy, butoxy, etc. Examples thereof include an alkoxy group such as a group, a halogen atom such as a chlorine atom, and a phenyl group substituted by a substituent such as a hydroxyl group. The same applies to the aryl moiety in another substituent having an aryl moiety (such as an aryloxy group).
  • the alkyl group having 1 to 5 carbon atoms in the definition of R 1 , R 2 and R 3 may be any of a straight-chain or branched-chain alkyl group.
  • the alcohol / reanol group having a total carbon number of 3 to 6 is a methoxycarbonyl group.
  • Group, ethoxycarbonyl methyl group, propoxy Examples include a methoxy group, a methoxy group, a methoxy group, a methoxy carbonyl group, and the like.
  • the aryloxy groups in the definition of R 2 include p-methylenoxy group, p-methoxyenoxy group, and p-chloro.
  • the hydroxyalkyl group having 1 to 3 carbon atoms includes a hydroxymethyl group and a 2-hydroxy group.
  • Examples include a styrene group and a 3-hydroxypropyl group.
  • cycloalkyl groups having 5 carbon atoms and 7 carbon atoms include cyclopentyl groups, cyclohexyl groups, and cycloalkyl groups.
  • the number of carbon atoms in the substitution group of the phenyl group is 1 or more, and the 5 alkoxy groups are methoxy group or ethoxy group.
  • Examples of the alkoxycarbonyl group include methoxycarbonyl group, ethoxycarbonyl group, propoxy group, and carbonyl group.
  • Butoxycarbonyl groups and the like are mentioned, and as alkylalkylcapto groups having 1 to 3 carbon atoms, methylmelcapto groups and Examples thereof include a methylcapto group and a propylmercapto group.
  • alkylamino group having 1 to 4 carbon atoms a methylamino group is exemplified.
  • Base Etch Lumino Group
  • Prop Examples of the amino group include a lumino group, a butylamino group, and the like, and a dimethylamino group, a genamino group, and a dimethylamino group having a total carbon number of 2 to 8 are exemplified.
  • Examples include a chloroamino group, a dipropylamino group, and a dibutylamino group.
  • Penge note 3 Memories 1 — Pyrazolin 1 5 — One;
  • a free form compound represented by the formula (I) or a physiologically acceptable salt may be used.
  • Physiologically acceptable salts include salts with mineral acids such as hydrochloric acid, sulfuric acid, hydrogen bromide, and linoleic acid; methanophorenoic acid, p-tonorenose / Levonic acid, benzenesulphonic acid, acetic acid, glycolic acid, glucuronic acid, maleic acid, fumaric acid, oxalic acid, ascorbic acid Salts with organic acids such as binic acid, citric acid, salicylic acid, nicotinic acid, tartaric acid; Alkali metals such as sodium and potassium Salts with alkaline earth metals such as magnesium and calcium; ammonium, tris (hydroxymethyl) amine Tan, N, N—vis (hydroxy) piperazine, 2—amino 2—methyl 1-prono. Salts with amines such as knoll, ethanolamine,
  • the active ingredient of the medicinal product of the present invention is a compound represented by the above formula (I) or a physiologically acceptable compound thereof.
  • a salt hydrate, a compound represented by the above formula (I) or a physiologically acceptable salt solvate of the compound represented by the above formula (I) may be used.
  • the type of organic solvent that forms the solvate is not particularly limited, but examples include, but are not limited to, methanol, ethanol, ether, dioxane, and teroxane. You can use force S to illustrate, for example, transhydran.
  • the compound represented by the above formula (I) may have one or more asymmetric carbons depending on the type of the substituent, and may be an optical isomer or There may be stereoisomers, such as diastereoisomers.
  • the active ingredient of the medicament of the present invention may be a pure form of a stereoisomer, an arbitrary mixture of stereoisomers, a racemic body, or the like.
  • the pyrazolone derivative of the formula (I) used in the present invention can be synthesized by any suitable method. Examples of the preferred synthesis method are described in the official gazette of Japanese Patent Application Publication No. Sho 62-1088814 and the official gazette of Tokuhei Hei 5-3 1532 There are several methods.
  • the preservative for a heart for transplantation or the preservative for an organ for transplantation is one or two or more of the compound of the formula (I) or a salt thereof as an active ingredient.
  • the above can be used as is, but preferably, the active ingredient and the pharmacologically and pharmaceutically acceptable additives are removed and the results obtained by those skilled in the art. It can be provided as a preservation solution in a known form.
  • the preservative for the heart for transplantation and the preservative for the organ for transplantation are provided as a preservation solution for the heart for transplantation and a preservation solution for the organ for transplantation, they may be used as additives.
  • a solubilizer or a solubilizing agent such as physiological saline, propylene glycol, etc .; glucose, sodium salt, D-mannini.
  • Tonicity agents such as tall glycerin; pH regulators such as inorganic acids, organic acids, inorganic bases or organic bases; phosphate buffered saline, citrate buffer, etc.
  • Physiologically acceptable buffers, stabilizing agents and the like can be used.
  • the present invention is used together with Euro-coln solution or UW solution which has been clinically used as a preservation solution for organs for transplantation. This is not required, but does not prevent the combination.
  • the organ to be transplanted is a kidney, the one containing Euro-Clins solution is outside the field of the present invention.
  • Glycine, ⁇ -ketoglutamic acid, hydroxyshatchi starch and the like can also be added.
  • concentration of the above active ingredient is not particularly limited, In the case of ketoglutamic acid, it is generally in the range of about 0.1 to about 10 mM, preferably about 2 mM. In the case of H, it is generally in the range of 3 to 7.5%, preferably about 5%.
  • the transplanted organ including the extracted heart for transplantation, is immersed in the preservation solution of the above embodiment, and preferably stored at about 4 ° C. until transplantation. It is preferred that the transplanted organs be immersed in the above preservation solution after having been subjected to an initial washing operation.
  • the preservation solution of the above embodiment can be used for final washing immediately before transplantation. When using the above preservation solution as a washing solution, it is preferable to cool it to about 4 ° C in advance.
  • the inhibitor of ischemia-reperfusion injury after heart transplantation and the inhibitor of ischemia-reperfusion injury after organ transplantation of the present invention include the compounds of the above formula (I) which are active ingredients.
  • one or more of the salts may be administered to the patient as is, but preferably, the active ingredient is pharmacologically and pharmaceutically acceptable.
  • Such additives can be provided as a formulation in a form known to those skilled in the art.
  • an oral administration preparation It can be used as a parenteral dosage form, preferably a parenteral dosage form, and more preferably an injection or infusion preparation Intravascular preparations that can be selected from these are listed.
  • Formulations suitable for oral administration include pharmacologically and pharmaceutically acceptable excipients such as glucose, lactose, D-mannitol, and denitol.
  • Excipients such as starch or crystallized cellulose; carboxymethyl cellulose, starch, or force / repoxymethyl / resin Disintegrant or disintegration aid for cellulose, calcium, etc .; hydroxypropyl cellulose, hydroxypropyl methylcellulose Binders such as Lurose, Polyvinylpyrrolidone, or Gelatin; Lubricants such as magnesium stearate or talc A core of hydroxypropyl methylenolose, sucrose, polyethylene glycol or titanium oxide; Tenting agent; ⁇ serine, flowing nod.
  • Bases such as raffin, polyethylene glycol, gelatin, kaolin, glycerin, purified water, or hard fat
  • Formulations suitable for injection and infusion include water-based injection solutions such as distilled water for injection, physiological saline, and propylene glycol, or dissolvable injections.
  • Solubilizers or solubilizers that can be formed; isotonic agents such as pudose, sodium chloride, and D-mannitol glycerin; inorganic acids , A pH adjusting agent such as an organic acid, an inorganic base or an organic base, and a pharmaceutical additive such as a stabilizing agent.
  • the above-mentioned commercial preparations can be used as they are for the ischemia-reperfusion injury inhibitor after organ transplantation.
  • the target of administration of the ischemia-reperfusion inhibitor after heart transplantation and the ischemia-reperfusion inhibitor after organ transplantation in the present invention are not particularly limited. No.
  • the force S which can be administered to both the organ donor and the recipient, should be administered to the recipient, preferably.
  • the administration route of the above-mentioned medicine is not particularly limited, and the force S that can be administered orally or non-orally is preferably administered non-orally. It is more preferably administered intravascularly.
  • it may be administered to a recipient during and / or after transplantation of the recipient, and preferably in the heart transplanted into the recipient. Administer immediately before ischemia perfusion when flow is restored.
  • it is not essential for the organ donor to administer before or after surgery to remove the organ to be transplanted, or Z, but it is necessary to administer it to the organ donor. It is not something that will prevent you from doing so.
  • the dose of the ischemia / reperfusion injury inhibitor after heart transplantation and the ischemia / reperfusion injury inhibitor after organ transplantation depends on the degree of preservation of the transplanted organ. Although it can be appropriately selected according to conditions such as the organ donor and the condition of the recipient, it is generally recommended that an adult be injected with about 0.1 mg / kg or about 100 mg Z kg for an adult. It is preferable to administer the drug by infusion or to give a dose of about 0.1 mg / kg from 0.1 force orally. In the case of administration by injection, for example, it is preferable to use, for example, an injection described in Japanese Patent Application Laid-Open No. 63-133283. .
  • the pharmaceuticals of the present invention has high safety (mouse intraperitoneally administered LD 5, 0.22 mg Z kg; rat oral administration LD 5, 3, 5) . 500 mg / kg: Registryof Toci E ffectsof Chemical S ubstances, 19
  • heart transplantation was performed using a pyrazolone derivative represented by the above formula (I) or a physiologically acceptable salt thereof.
  • the organ to be transplanted is a kidney, the transplantation method does not include Eurocoln's solution.
  • CPK—MB Creatine phosphokinase —'MB
  • CPK — MB The 30-minute value is subtracted from the 60-minute value, and the resulting value is 1 — F for the control / ray group 284.0 ⁇ 151.4 ng / ml.
  • a preservative for heart transplantation an agent for suppressing ischemia-reperfusion injury after heart transplantation, and a preservative for organs for transplantation that do not contain Euro-cold solution ⁇ It is possible to provide a suppressor of ischemia-reperfusion injury after organ transplantation, which does not contain Eurocoln's solution. Further, it is possible to provide a heart transplantation method and an organ transplantation method characterized by not containing Eurocoln's solution. This application was filed with a priority claim on Japanese Patent Application No. 2002-39554.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Dentistry (AREA)
  • Zoology (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biophysics (AREA)
  • Physiology (AREA)
  • Epidemiology (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des agents permettant de conserver un coeur destiné à être transplanté ainsi que des agents permettant de prévenir une lésion ischémique au retour de la perfusion consécutive à une transplantation cardiaque qui contiennent, en tant que principe actif, des dérivés de pyrazolone représentés par la formule générale (I). D'une manière plus spécifique, l'invention concerne des agents permettant de conserver un coeur destiné à être transplanté ainsi que des agents permettant de prévenir une lésion ischémique au retour de la perfusion consécutive à une transplantation cardiaque qui contiennent, en tant que principe actif, des dérivés de pyrazolone représentés par la formule générale (I) mais ne contiennent pas de solution d'Euro-Colins. Dans ladite formule, R1 représente alkyle C1-5, etc. ; R2 représente hydrogène, etc. ; et R3 représente phényle, etc.
PCT/JP2003/001554 2002-02-15 2003-02-14 Medicaments destines a etre utilises dans la transplantation d'organes WO2003067979A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2003567178A JPWO2003067979A1 (ja) 2002-02-15 2003-02-14 臓器移植時に用いる薬剤
AU2003211983A AU2003211983A1 (en) 2002-02-15 2003-02-14 Drugs to be used in organ transplantation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002-39354 2002-02-15
JP2002039354 2002-02-15

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WO2003067979A1 true WO2003067979A1 (fr) 2003-08-21

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010087306A1 (fr) 2009-01-29 2010-08-05 株式会社林原生物化学研究所 Agent anti-maladie neurodégénérative
WO2018097225A1 (fr) * 2016-11-25 2018-05-31 テルモ株式会社 Liquide de conservation de cellules vivantes ou de composition contenant des cellules vivantes

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0952801A (ja) * 1995-08-10 1997-02-25 Mitsubishi Chem Corp 移植臓器保存剤

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0952801A (ja) * 1995-08-10 1997-02-25 Mitsubishi Chem Corp 移植臓器保存剤

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MINHAZ U. ET AL.: "Effect of MCI-186 on postischemic reperfusion injury in isolated rat heart", FREE RADICALS RESEARCH, vol. 24, no. 5, 1996, pages 361 - 367, XP002962137 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010087306A1 (fr) 2009-01-29 2010-08-05 株式会社林原生物化学研究所 Agent anti-maladie neurodégénérative
WO2018097225A1 (fr) * 2016-11-25 2018-05-31 テルモ株式会社 Liquide de conservation de cellules vivantes ou de composition contenant des cellules vivantes
JPWO2018097225A1 (ja) * 2016-11-25 2019-10-17 テルモ株式会社 生細胞または生細胞を含む組成物の保存液

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JPWO2003067979A1 (ja) 2005-06-02

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