WO2011149012A1 - Agent prophylactique ou thérapeutique pour maladies de dénaturation rétinienne/choroïdienne comprenant un dérivé d'isoquinolinesulfonyle comme principe actif, procédé prophylactique ou thérapeutique pour maladies de dénaturation rétinienne/choroïdienne, et dérivé d'isoquinolinesulfonyle ou son sel pharmaceutiquement acceptable, et utilisation associée - Google Patents
Agent prophylactique ou thérapeutique pour maladies de dénaturation rétinienne/choroïdienne comprenant un dérivé d'isoquinolinesulfonyle comme principe actif, procédé prophylactique ou thérapeutique pour maladies de dénaturation rétinienne/choroïdienne, et dérivé d'isoquinolinesulfonyle ou son sel pharmaceutiquement acceptable, et utilisation associée Download PDFInfo
- Publication number
- WO2011149012A1 WO2011149012A1 PCT/JP2011/062072 JP2011062072W WO2011149012A1 WO 2011149012 A1 WO2011149012 A1 WO 2011149012A1 JP 2011062072 W JP2011062072 W JP 2011062072W WO 2011149012 A1 WO2011149012 A1 WO 2011149012A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- choroidal
- retinal
- macular degeneration
- related macular
- disease
- Prior art date
Links
- UNGSQNVCWUJGPM-UHFFFAOYSA-N O=S(C1CCNCCC1)(c1cccc2c1ccnc2)=O Chemical compound O=S(C1CCNCCC1)(c1cccc2c1ccnc2)=O UNGSQNVCWUJGPM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- the present invention relates to a preventive or therapeutic agent for a retina choroidal degenerative disease substantially free of angiogenesis, which contains at least one of a specific isoquinoline sulfonyl derivative or a pharmaceutically acceptable salt thereof as an active ingredient.
- the present invention also relates to a method for preventing or treating the choroidal degenerative disease using such an isoquinoline sulfonyl derivative or a pharmaceutically acceptable salt thereof.
- the present invention also relates to an isoquinoline sulfonyl derivative or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of the retina choroidal degenerative disease.
- the present invention further relates to the use of such an isoquinoline sulfonyl derivative or a pharmaceutically acceptable salt thereof for producing a prophylactic or therapeutic agent for the above-mentioned choroidal degenerative disease.
- age-related macular degeneration is a major cause of blindness in middle to old age in developed countries such as Japan, the United States, and Europe. It has become.
- Age-related macular degeneration is a disease caused by aging of the macular region, and the number of patients is steadily increasing at present as an aging society.
- Age-related macular degeneration is roughly classified into wet type with neovascularization from the choroid and dry type without neovascularization that occurs from the choroid.
- the former exudative type is laser photocoagulation.
- Treatments such as surgery, neovascularization, and foveal movement have been performed, but these treatments have limitations.
- Treatment with an angiogenesis inhibitor bevacizumab [bevacizumab, trade name: Avastin], ranibizumab [tradename: Lucentis] or the like has also been performed.
- bevacizumab an angiogenesis inhibitor bevacizumab [bevacizumab, trade name: Avastin]
- ranibizumab [tradename: Lucentis] or the like has also been performed.
- the compound represented by the following general formula (1) is generally called Fasudil and is known as an active ingredient of Eryel (trade name) intravenous infusion, which is a therapeutic agent for brain dysfunction. It has been.
- isoquinoline sulfonamide derivatives containing fasudil act on mammalian vascular smooth muscle, vasodilators, cerebral circulation improving agents, angina pectoris, cerebrovascular thrombosis and hypertension preventive or therapeutic agent Is useful as US Pat. No. 4,678,783 (Patent Document 1). Furthermore, the production method and vasodilating action of these derivatives are described in Chem. Pharm. Bull. , 40 (3) 770-773 (1992) (Non-patent Document 1), its Rho kinase inhibitory action is reported in Am. J. et al. Physiol. Cell Physiol.
- Non-patent Document 2 Non-patent Document 2
- its angiogenesis inhibitory action is described in Mol. Cancer Ther. , 6 (5) 1517-1525 (2007) (non-patent document 3)
- its use as a therapeutic agent for eye diseases such as glaucoma and retinopathy is described in WO 97/23222 (patent document 2).
- a retina choroidal degenerative disease substantially free of new blood vessels, such as atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa
- atrophic age-related macular degeneration such as atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa
- Recurrent choroidal degenerative disease substantially free of new blood vessels such as atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, cerebral rotational retinal choroidal atrophy, and retina choroid associated with those diseases
- Finding drugs that have preventive or therapeutic effects on disorders is a very interesting task.
- the present inventors have a retina choroidal degenerative disease substantially free of neovascularization, for example, atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, brain retinal choroidal atrophy or those diseases
- atrophic age-related macular degeneration for example, atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, brain retinal choroidal atrophy or those diseases
- isoquinoline sulfonyl derivatives or their salts were found to be effective against photoreceptor cell death and / or photoreceptor cell death in a mouse photodamage model.
- the inventors have found that they have a suppressing effect, and have reached the present invention. That is, the present invention is as follows.
- the present invention relates to prevention or treatment of a retina choroidal degenerative disease substantially free of neovascularization, comprising at least one of the compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient. It is an agent.
- the compound represented by the following formula (1) or a salt thereof is referred to as “the compound of the present invention”.
- the present invention also provides a method for preventing or treating a choroidal degenerative disease substantially free of new blood vessels, comprising administering to a patient a pharmacologically effective amount of at least one of the compounds of the present invention.
- the present invention also provides the compound of the present invention for use in the prevention or treatment of a retina choroidal degenerative disease substantially free of neovascularization.
- the present invention further provides use of the compound of the present invention for producing a prophylactic or therapeutic agent for a retina choroidal degenerative disease substantially free of new blood vessels.
- the retina choroidal degenerative disease in the present invention is atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, cerebral rotational retinal choroidal atrophy, central retinal artery occlusion, central retinal vein occlusion, retinal pigment At least one selected from the group consisting of epithelial detachment, central serous chorioretinopathy, polypoidal choroidal vasculopathy, multiple choroiditis, uveitis (Behcet's disease, Harada disease) and recurrent choroidal disorders associated with those diseases
- it is selected from the group consisting of atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, cerebral rotational retinal choroidal atrophy and reticulochoroidal disorders associated with those diseases
- Particularly preferred is at least one.
- the compound of the present invention is a retina choroidal degenerative disease substantially free of new blood vessels, such as atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, cerebral rotational retinal choroidal atrophy, central retinal artery occlusion , Central retinal vein occlusion, retinal pigment epithelial detachment, central serous chorioretinopathy, polypoidal choroidal vasculopathy, multiple choroiditis, uveitis (Behcet's disease, Harada disease), and associated with these diseases (Preferably atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, brain retinal choroidal atrophy and retina choroidal disorders associated with these diseases, particularly preferably atrophic type It is useful as a preventive or therapeutic agent for age-related macular degeneration and retina choroid disorder associated with the disease.
- a method for preventing or treating the choroidal degenerative disease using the compound of the present invention, a compound of the present invention for use in preventing or treating the choroidal degenerative disease, and a prophylactic or therapeutic agent for the choroidal degenerative disease Also provided is the use of a compound of the present invention to accomplish this.
- the present invention contains at least one of the isoquinoline sulfonyl derivative represented by the following general formula (1) or a pharmaceutically acceptable salt thereof (the compound of the present invention) as an active ingredient, and is substantially free from angiogenesis. It is a preventive or therapeutic agent for choroidal degenerative diseases.
- the compound of the present invention has an inhibitory effect on photoreceptor cell death and / or photoreceptor cell death in a mouse photodamage model.
- Such a compound of the present invention is useful as a prophylactic or therapeutic agent for a retina choroidal degenerative disease substantially free of angiogenesis.
- a method for preventing or treating the choroidal degenerative disease using the compound of the present invention, the compound of the present invention for use in the prevention or treatment of the choroidal degenerative disease, and the choroidal degenerative disease is also provided. Also provided is the use of a compound of the invention for the manufacture of a prophylactic or therapeutic agent.
- the “salt” in the compound of the present invention is not particularly limited as long as it is a pharmaceutically acceptable salt, and is a salt with an inorganic acid such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid or the like.
- the hydrate and / or solvate is also included in the scope of the compound.
- the composition ratio of the free form of the compound of the present invention to the salt is 1: 1 or 1: when the salt is a monovalent inorganic acid or monovalent organic acid.
- the 2: 1 component ratio is when the salt is a trivalent inorganic acid or a trivalent organic acid, A composition ratio of 3: 1 is preferred.
- the composition ratio of the free form of the compound of the present invention, salt and water is as follows when the salt is a monovalent inorganic acid or monovalent organic acid:
- the composition ratio of 2: 1 or 1: 1: 3 is a divalent inorganic acid or divalent organic acid
- the composition ratio of 2: 1: 1 or 2: 1: 6 is Is a trivalent inorganic acid or a trivalent organic acid
- a composition ratio of 6: 2: 3 or 3: 1: 9 is preferred.
- crystal polymorph group refers to various crystal forms depending on conditions and states (including the formulated state in this state) such as production, crystallization, and storage of these crystals. It means the crystal form and the whole process at each stage when changing.
- Preferred examples of the compound of the present invention include the following compounds or pharmaceutically acceptable salts thereof.
- this invention compound can be manufactured in accordance with the normal method in the field
- the “retina choroidal degenerative disease substantially free of new blood vessels” in the present invention means atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, cerebral rotational retinal choroidal atrophy, central retinal artery occlusion , Central retinal vein occlusion, retinal pigment epithelial detachment, central serous chorioretinopathy, polypoidal choroidal vasculopathy, multiple choroiditis, uveitis (Behcet's disease, Harada disease) and the choroid associated with these diseases And at least one selected from the group consisting of disorders, preferably atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, cerebral rotational retinal choroidal atrophy, and networks associated with these diseases At least one selected from the group consisting of choroidal disorders, particularly preferably at least one selected from the group consisting of atrophic age-related macular degeneration
- preventive or therapeutic agent of the present invention uses a widely used technique as a single preparation and / or combination preparation by adding other pharmaceutically acceptable active ingredients and / or additives as necessary. Can be formulated.
- the prophylactic or therapeutic agent of the present invention can be administered to a patient orally or parenterally.
- the administration form includes oral administration, topical administration to the eye (instillation administration, intraconjunctival sac administration, intravitreal administration). , Subconjunctival administration, subtenon administration, etc.), intravenous administration, transdermal administration, etc., and if necessary, formulated with a pharmaceutically acceptable additive into a dosage form suitable for administration.
- dosage forms suitable for oral administration include tablets, capsules, granules, fine granules, powders, etc.
- dosage forms suitable for parenteral administration include injections, eye drops, and eyes.
- An ointment, a patch, a gel, an insertion agent, etc. are mentioned. These can be prepared using conventional techniques widely used in the field.
- the preventive or therapeutic agent of the present invention can also be made into preparations for DDS (drug delivery system) such as preparations for intraocular implants and microspheres.
- DDS drug delivery
- tablets are made of excipients such as lactose, glucose, D-mannitol, anhydrous calcium hydrogen phosphate, starch, sucrose; carboxymethylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, crospovidone, starch, partially pregelatinized starch ,
- Disintegrating agents such as low-substituted hydroxypropylcellulose; binders such as hydroxypropylcellulose, ethylcellulose, gum arabic, starch, partially pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol; magnesium stearate, calcium stearate, talc, hydrous silicon dioxide ,
- Lubricants such as hydrogenated oil; refined sucrose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, pyrrolidone, etc.
- Coating agents citric acid, aspartame, ascorbic acid, using appropriately selected and flavoring agents such as menthol, can be prepared.
- the injection is selected as necessary from an isotonic agent such as sodium chloride; a buffering agent such as sodium phosphate; a surfactant such as polyoxyethylene sorbitan monooleate; a thickener such as methylcellulose.
- an isotonic agent such as sodium chloride
- a buffering agent such as sodium phosphate
- a surfactant such as polyoxyethylene sorbitan monooleate
- a thickener such as methylcellulose.
- Eye drops include isotonic agents such as sodium chloride and concentrated glycerin; buffering agents such as sodium phosphate and sodium acetate; surface activity such as polyoxyethylene sorbitan monooleate, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil Agents; Stabilizers such as sodium citrate and sodium edetate; Preservatives such as benzalkonium chloride and paraben can be selected and used as necessary, and pH is acceptable for ophthalmic preparations Although it may be within the range, it is usually preferably within the range of 4-8.
- the eye ointment can be prepared using a commonly used base such as white petrolatum or liquid paraffin.
- the intercalating agent is prepared by crushing and mixing a biodegradable polymer, for example, a biodegradable polymer such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, and polyacrylic acid, with the compound of the present invention, and compressing the powder. If necessary, excipients, binders, stabilizers, and pH adjusters can be used.
- a biodegradable polymer for example, a biodegradable polymer such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, and polyacrylic acid
- the preparation for an intraocular implant can be prepared using a biodegradable polymer, for example, a biodegradable polymer such as polylactic acid, polyglycolic acid, lactic acid / glycolic acid copolymer, and hydroxypropylcellulose.
- a biodegradable polymer such as polylactic acid, polyglycolic acid, lactic acid / glycolic acid copolymer, and hydroxypropylcellulose.
- the dose of the preventive or therapeutic agent of the present invention can be appropriately changed according to the dosage form, the severity of the patient's symptoms to be administered, age, weight, doctor's judgment, etc.
- 0.01 to 5000 mg, preferably 0.1 to 2500 mg, more preferably 0.5 to 1000 mg per day can be administered to adults in one or several divided doses.
- the active ingredient concentration of w / v) can be administered once or several times a day.
- a patch containing 0.0001 to 2000 mg can be applied to an adult.
- a patch containing 0.0001 to 2000 mg can be applied to an adult.
- an intraocular implant preparation 0.0001 to 2000 mg is included for an adult.
- An intraocular implant formulation can be implanted in the eye.
- Compound A ′ The pharmacological effect of Compound A dihydrochloride (hereinafter also referred to as “Compound A ′”) was evaluated using a mouse photopathy model.
- the mouse photopathy model is a model animal in which cell death of retinal photoreceptor cells and / or photoreceptors is induced by light irradiation, and is a retina choroidal degenerative disease substantially free of new blood vessels, for example, atrophic addition. It is widely used as a model animal for age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, etc. (Invest. Ophthalmol. Vis. Sci., 2005; 46: 979-987).
- Amplitude attenuation suppression rate (%) ((V x ⁇ V 0 ) / (V n ⁇ V 0 )) ⁇ 100
- V 0 Amplitude of base administration group ( ⁇ V)
- V n amplitude of normal control group ( ⁇ V)
- V x Amplitude of compound A ′ administration group ( ⁇ V) (Method of administration) 1)
- Single administration before light irradiation Compound A administration group: 1% (w / v) Compound A ′ solution suspended in an aqueous methylcellulose solution at a dose of 10 mg / kg, once 1 hour before light irradiation, Orally administered.
- Normal control group and base administration group A 1% (w / v) methylcellulose aqueous solution was orally administered 1 hour before light irradiation.
- the compound of the present invention represented by Compound A ′ suppresses photoreceptor cell death and / or photoreceptor cell death. Therefore, the compound of the present invention has a prophylactic or therapeutic effect for a choroidal degenerative disease substantially free of neovascularization.
- formulation example The pharmaceutical agent of the present invention will be described more specifically with formulation examples, but the present invention is not limited to these formulation examples.
- the compound of the present invention is a retina choroidal degenerative disease substantially free of new blood vessels, such as atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, cerebral rotational retinal choroidal atrophy, retinal center Arterial occlusion, central retinal vein occlusion, retinal pigment epithelial detachment, central serous chorioretinopathy, polypoidal choroidal vasculopathy, multiple choroiditis, uveitis (Behcet's disease, Harada disease), and those diseases (Preferably atrophic age-related macular degeneration, early age-related macular degeneration, retinitis pigmentosa, cerebral rotational retinal choroidal atrophy, and retina choroid disorder associated with these diseases, particularly preferably atrophy It is useful as a prevent
Abstract
La présente invention concerne un composé représenté par une formule générale (1) ou un sel de celui-ci présentant un effet inhibiteur sur la mort des photorécepteurs et/ou la mort des cellules visuelles dans un modèle de souris à sensibilité induite par la lumière, et peut servir, par conséquent, d'agent prophylactique ou thérapeutique pour les maladies de dénaturation rétinienne/choroïdienne qui n'impliquent sensiblement pas de néovascularisation (par ex., dégénérescence maculaire liée à l'âge de forme atrophique, rétinite pigmentaire, atrophie gyrée de la choroïde et de la rétine) et des troubles rétiniens et choroïdiens associés aux maladies susmentionnées.
Applications Claiming Priority (2)
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JP2010121823 | 2010-05-27 | ||
JP2010-121823 | 2010-05-27 |
Publications (1)
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WO2011149012A1 true WO2011149012A1 (fr) | 2011-12-01 |
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PCT/JP2011/062072 WO2011149012A1 (fr) | 2010-05-27 | 2011-05-26 | Agent prophylactique ou thérapeutique pour maladies de dénaturation rétinienne/choroïdienne comprenant un dérivé d'isoquinolinesulfonyle comme principe actif, procédé prophylactique ou thérapeutique pour maladies de dénaturation rétinienne/choroïdienne, et dérivé d'isoquinolinesulfonyle ou son sel pharmaceutiquement acceptable, et utilisation associée |
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JP (1) | JP2012006918A (fr) |
WO (1) | WO2011149012A1 (fr) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5557408B1 (ja) * | 2013-04-24 | 2014-07-23 | 国立大学法人九州大学 | 眼底疾患治療剤 |
WO2015002061A1 (fr) * | 2013-07-04 | 2015-01-08 | 日本曹達株式会社 | Dérivé de phénylimidazole, et médicament thérapeutique ou médicament préventif d'une maladie inflammatoire, etc. |
JP2015523546A (ja) * | 2012-05-01 | 2015-08-13 | トランスレイタム メディカス インコーポレイテッド | 失明性疾患を処置および診断するための方法 |
EP3006028A1 (fr) * | 2014-10-06 | 2016-04-13 | Samsung Electronics Co., Ltd | Composition permettant la réduction de la sénescence cellulaire comprenant un inhibiteur de rho-kinase et son utilisation |
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JP2006327942A (ja) * | 2005-05-23 | 2006-12-07 | Chiba Univ | 軸索再生剤 |
JP2008247923A (ja) * | 2001-04-11 | 2008-10-16 | Senju Pharmaceut Co Ltd | 視覚機能障害改善剤 |
JP2009513660A (ja) * | 2005-10-26 | 2009-04-02 | 旭化成ファーマ株式会社 | 肺動脈性高血圧の治療用併用療法におけるファスジル |
WO2010010702A1 (fr) * | 2008-07-24 | 2010-01-28 | 国立大学法人大阪大学 | Agent prophylactique ou thérapeutique pour la myopie axiale |
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2011
- 2011-05-26 JP JP2011118030A patent/JP2012006918A/ja not_active Withdrawn
- 2011-05-26 WO PCT/JP2011/062072 patent/WO2011149012A1/fr active Application Filing
Patent Citations (4)
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JP2008247923A (ja) * | 2001-04-11 | 2008-10-16 | Senju Pharmaceut Co Ltd | 視覚機能障害改善剤 |
JP2006327942A (ja) * | 2005-05-23 | 2006-12-07 | Chiba Univ | 軸索再生剤 |
JP2009513660A (ja) * | 2005-10-26 | 2009-04-02 | 旭化成ファーマ株式会社 | 肺動脈性高血圧の治療用併用療法におけるファスジル |
WO2010010702A1 (fr) * | 2008-07-24 | 2010-01-28 | 国立大学法人大阪大学 | Agent prophylactique ou thérapeutique pour la myopie axiale |
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LIMEI YIN ET AL.: "Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo", MOL. CANCER. THER., vol. 6, 2007, pages 1517 - 1525, XP055260964, DOI: doi:10.1158/1535-7163.MCT-06-0689 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015523546A (ja) * | 2012-05-01 | 2015-08-13 | トランスレイタム メディカス インコーポレイテッド | 失明性疾患を処置および診断するための方法 |
JP5557408B1 (ja) * | 2013-04-24 | 2014-07-23 | 国立大学法人九州大学 | 眼底疾患治療剤 |
EP2990040A4 (fr) * | 2013-04-24 | 2017-07-05 | Kyushu University, National University Corporation | Agent thérapeutique pour maladie du fond de l'oeil |
US10426783B2 (en) | 2013-04-24 | 2019-10-01 | Kyushu University, Nat'l University Corporation | Therapeutic agent for ocular fundus disease |
EP3626245A1 (fr) * | 2013-04-24 | 2020-03-25 | Kyushu University, National University Corporation | Agent thérapeutique pour maladie ophtalmique |
WO2015002061A1 (fr) * | 2013-07-04 | 2015-01-08 | 日本曹達株式会社 | Dérivé de phénylimidazole, et médicament thérapeutique ou médicament préventif d'une maladie inflammatoire, etc. |
CN105324366A (zh) * | 2013-07-04 | 2016-02-10 | 日本曹达株式会社 | 苯基咪唑衍生物以及炎症性疾病等的治疗药或预防药 |
EP3006028A1 (fr) * | 2014-10-06 | 2016-04-13 | Samsung Electronics Co., Ltd | Composition permettant la réduction de la sénescence cellulaire comprenant un inhibiteur de rho-kinase et son utilisation |
US9943525B2 (en) | 2014-10-06 | 2018-04-17 | Samsung Electronics Co., Ltd. | Composition for reducing cell senescence comprising Rho-kinase inhibitor and use thereof |
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JP2012006918A (ja) | 2012-01-12 |
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