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WO2009110526A1 - Agent prophylactique ou thérapeutique pour les troubles du nerf optique, qui comprend du 3',5-di-2-propényl-(1,1'-biphényl)-2,4'-diol en tant que principe actif - Google Patents

Agent prophylactique ou thérapeutique pour les troubles du nerf optique, qui comprend du 3',5-di-2-propényl-(1,1'-biphényl)-2,4'-diol en tant que principe actif Download PDF

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Publication number
WO2009110526A1
WO2009110526A1 PCT/JP2009/054122 JP2009054122W WO2009110526A1 WO 2009110526 A1 WO2009110526 A1 WO 2009110526A1 JP 2009054122 W JP2009054122 W JP 2009054122W WO 2009110526 A1 WO2009110526 A1 WO 2009110526A1
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WIPO (PCT)
Prior art keywords
ester
propenyl
biphenyl
diol
optic neuropathy
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Ceased
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PCT/JP2009/054122
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English (en)
Japanese (ja)
Inventor
正顕 笹岡
寿之 清家
正明 景山
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Santen Pharmaceutical Co Ltd
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Santen Pharmaceutical Co Ltd
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Publication of WO2009110526A1 publication Critical patent/WO2009110526A1/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/205—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings
    • C07C39/21—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings with at least one hydroxy group on a non-condensed ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • 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
    • A61P27/06—Antiglaucoma agents or miotics
    • 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

  • optic neuropathy containing as an active ingredient at least one of 3 ', 5-di-2-propenyl- (1,1'-biphenyl) -2,4'-diol, an ester thereof or a salt thereof
  • the present invention relates to an agent, a retinal neuronal cell death inhibitor, or a neurofilament light chain expression level recovery agent.
  • the retina consists of 10 layers: inner boundary membrane, nerve fiber layer, ganglion cell layer, inner reticular layer, inner granular layer, outer reticular layer, outer granular layer, outer boundary membrane, photoreceptor layer and retinal pigment epithelial layer
  • the tissue is 0.1 to 0.5 mm in size, and includes retinal neurons such as photoreceptor cells, bipolar cells, ganglion cells, horizontal cells and amacrine cells.
  • Retinal neurons play an important role in the reception and transmission of visual information, such as converting light stimuli into electrical signals and transmitting them to the brain.
  • visual information entered from the eyes is converted into an electrical signal by the photoreceptor cell and transmitted to the ganglion cell after passing through the horizontal cell, the bipolar cell and / or the amacrine cell.
  • the electrical signal is then transmitted to the brain via the optic nerve, which is a bundle of optic nerve fibers containing ganglion cell axons.
  • optic nerve damage There are various possible causes of optic nerve damage, but the main causes include 1) increased intraocular pressure, 2) retinal blood flow circulatory disorder / retinal ischemia, 3) increased excitatory amino acids, etc. It is thought that the optic nerve is impaired by the activation of the accompanying glutamate signal cascade, axonal damage of retinal ganglion cells, and subsequent apoptosis of retinal neurons.
  • N-methyl-D-aspartate an agent that suppresses apoptosis of retinal neurons and protects the retinal neurons, that is, a glutamate neurotoxicity inhibitor, N-methyl-D-aspartate (hereinafter referred to as “N-methyl-D-aspartate”)
  • Drugs such as receptor blockers and nitric oxide synthesis inhibitors are thought to be useful as preventive or therapeutic agents for optic neuropathy and associated eye diseases, and various studies have been made. Yes.
  • Patent Document 1 discloses a retinal nerve cell protective agent containing nipradilol, which is one of ⁇ -blockers, as an active ingredient.
  • Patent Document 2 discloses optic ganglion cell protection containing an interleukin-1 receptor antagonist protein as an active ingredient.
  • Patent Document 3 discloses an optic ganglion cell protective agent containing an ⁇ 1 receptor blocker such as bunazosin as an active ingredient, and
  • Patent Document 4 discloses retinal nerve cell protection containing a fluorinated prostaglandin F2 ⁇ derivative as an active ingredient.
  • Patent Document 5 discloses a retinal nerve cell protective agent containing an indazole derivative as an active ingredient.
  • Representative eye diseases with optic neuropathy include glaucoma, glaucomatous visual field stenosis, glaucomatous optic nerve atrophy, glaucomatous optic neuropathy, central retinal artery occlusion, branch retinal artery occlusion, central retinal vein occlusion, retina Venous branch occlusion, diabetic retinopathy, macular degeneration (age-related macular degeneration such as dry age-related macular degeneration), retinitis pigmentosa, retinopathy of prematurity, retinal detachment, retinal pigment Examples include glaucomatous diseases such as epithelial detachment, label disease, and ischemic optic neuropathy, retinal diseases, and ischemic disorders.
  • non-patent document 1 As its pharmacological action, non-patent document 1, non-patent document 2 or non-patent document 3 show persistent central inhibitory action such as sedation, movement inhibitory action, central muscle relaxation action, spinal cord reflex inhibition, etc.
  • Non-patent document 4 or non-patent document 5 discloses an anti-gastric ulcer effect in non-patent document 6, anti-bacterial activity against gram-positive bacteria disclosed in non-patent document 7, and cranial nerve cell protective effect disclosed in non-patent document 8. .
  • Patent Document 6 discloses an angiogenesis inhibitory action of a honokiol type compound
  • Patent Document 7 discloses a cell growth inhibitory action.
  • Non-Patent Document 9 discloses that magnolol (one component contained in the herbal medicine), which is a structural isomer of honokiol, has an action of lowering intraocular pressure.
  • Finding is a very interesting task.
  • NMDA-induced rats In order to find a compound useful as a prophylactic or therapeutic agent for optic neuropathy, an inhibitor of retinal neuronal cell death, or a recovery agent for the expression level of neurofilament light chain, the present inventors have identified NMDA-induced rats. The effect on the retinopathy model was examined. As a result, 3 ′, 5-di-2-propenyl- (1,1′-biphenyl) -2,4′-diol, an ester thereof or a salt thereof was obtained as follows: Significantly suppresses the decrease in the number of cells in the retinal nerve cell layer upon oral administration in an NMDA-induced rat retinal disorder model, 2.
  • the “ester” means a compound in which one or both of the two hydroxy groups in the general formula (1) are esterified, and there is no particular limitation as long as the hydroxy group site is esterified.
  • the hydroxy group a lower alkyl carboxylic acid which may have a substituent
  • a lower alkyl sulfinic acid which may have a substituent
  • a lower alkyl which may have a substituent
  • An ester formed from a hydroxy group and an optionally substituted lower alkyl carboxylic acid is preferred.
  • the “salt thereof” means a pharmaceutically acceptable salt of “3 ′, 5-di-2-propenyl- [1,1′-biphenyl] -2,4′-diol or ester thereof”. However, there is no particular limitation as long as it is a pharmaceutically acceptable salt.
  • the salt formed with alkali metals, such as lithium, sodium, and potassium, is preferable.
  • the present compound preferably one of those compounds, as an active ingredient, or
  • the agent for recovering the expression level of a neurofilament light chain is the present invention.
  • optical neuropathy in the present invention means an optic neuropathy and / or an eye disease accompanied by an optic neuropathy.
  • the “eye disease with optic neuropathy” is not particularly limited as long as it is an eye disease with optic neuropathy, but examples include glaucomatous diseases, retinal diseases, ischemic disorders, and the like. , Glaucomatous visual field stenosis, glaucomatous optic nerve atrophy, glaucomatous optic neuropathy, central retinal artery occlusion, branch retinal artery occlusion, central retinal vein occlusion, branch retinal vein occlusion, diabetic retinopathy, macular degeneration ( Age-related macular degeneration such as dry age-related macular degeneration, wet age-related macular degeneration), retinitis pigmentosa, retinopathy of prematurity, retinal detachment, retinal pigment epithelial detachment, label disease, ischemic optic neuropathy .
  • Glaucomatous visual field stenosis glaucomatous optic nerve atrophy
  • glaucomatous optic neuropathy central retinal artery
  • “Glaucomatous optic neuropathy” in the present invention is not particularly limited as long as it is an optic neuropathy caused by glaucoma. Specifically, it means glaucoma and / or an eye disease associated with glaucoma, more specifically. Glaucoma and glaucomatous visual field stenosis, glaucomatous optic nerve atrophy, glaucomatous eye diseases such as glaucomatous optic neuropathy.
  • the “retinal nerve cell” in the present invention means a nerve cell involved in transmission of a visual signal to the brain, and specifically means a photoreceptor cell, a horizontal cell, a bipolar cell, an optic ganglion cell, an amacrine cell, and the like.
  • Retinal nerve cell death in the present invention means apoptosis and / or necrosis of retinal neurons.
  • neurofilament light chain expression level recovery agent in the present invention means an agent that suppresses and / or increases the decrease in the expression level of the neurofilament light chain in the retina.
  • This neurofilament light chain is one of the main components of the optic nerve axon and is an important component for maintaining the morphology of the optic nerve axon.
  • halogen refers to fluorine, chlorine, bromine or iodine.
  • lower alkyl refers to straight-chain or branched alkyl having 1 to 6 carbon atoms. Specific examples include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl groups and the like.
  • lower alkoxy refers to a hydroxy hydrogen atom substituted with lower alkyl. Specific examples include methoxy, ethoxy, n-propoxy, n-butoxy, n-pentoxy, n-hexyloxy, isopropoxy, isobutoxy, sec-butoxy, tert-butoxy, isopentoxy group and the like.
  • aryl refers to aryl having 6 to 10 carbon atoms. Specific examples include phenyl and naphthyl.
  • aryloxy refers to a hydroxy hydrogen atom substituted with aryl. Specific examples include phenyloxy and naphthyloxy.
  • lower alkyl which may have a substituent refers to an alkyl having one or more substituents selected from the group consisting of halogen, lower alkoxy, aryl and aryloxy.
  • aryl optionally having substituent (s) refers to aryl having one or more substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, aryl and aryloxy.
  • the “plurality” in the present invention may be the same or different, and the number is preferably 2 or 3, particularly preferably 2.
  • This compound may take the form of a hydrate or a solvate.
  • the crystalline polymorph is also included in the scope of the present invention.
  • the compound can be administered either orally or parenterally.
  • dosage forms include oral administration, topical ocular administration (instillation administration, intraconjunctival sac administration, intravitreal administration, subconjunctival administration, subtenon administration, etc.), intravenous administration, transdermal administration, etc.
  • a pharmaceutically acceptable additive can be appropriately selected and used, and can be formulated into a dosage form suitable for the administration form.
  • Examples of the dosage form include tablets, capsules, granules, powders and the like in the case of oral preparations, and examples of parenterals include injections, eye drops, eye ointments, patches, gels, inserts and the like. Can be mentioned.
  • excipients such as lactose, glucose, D-mannitol, anhydrous calcium hydrogen phosphate, starch, sucrose; carboxymethylcellulose, carboxymethylcellulose calcium, cloth Disintegrants such as carmellose sodium, crospovidone, starch, partially pregelatinized starch, low substituted hydroxypropylcellulose; binders such as hydroxypropylcellulose, ethylcellulose, gum arabic, starch, partially pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol ; Lubricants such as magnesium stearate, calcium stearate, talc, hydrous silicon dioxide, hydrogenated oil; refined sucrose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methyl Cellulose, ethyl cellulose, coating agents such as polyvinyl pyrrolidone; citric acid, aspartame, ascorbic acid
  • Injections are: isotonic agents such as sodium chloride; solvents or solubilizers such as soybean oil and macrogol; buffering agents such as sodium phosphate; surface activity such as polysorbate 80 Agents: Thickeners such as carmellose sodium and methylcellulose, etc., soothing agents such as benzyl alcohol, etc. can be appropriately selected and used as necessary, and their pH is acceptable for injections. If it is within the range, there is no particular problem, and a pH range of 4 to 8 is desirable.
  • Eye drops are castor oil, glycerol, alcohol, solvents or solubilizers such as ether compounds of polyglycerol and alcohol, isotonic agents such as sodium chloride and concentrated glycerin; phosphoric acid Buffers such as salts and carbonates; surfactants such as polyoxyethylene sorbitan monooleate, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil; stabilizers such as sodium citrate and sodium edetate; benzalco chloride
  • a dispersing agent such as a water-soluble polymer, a tonicity agent such as sodium chloride and concentrated glycerin
  • a buffering agent such as phosphate and carbonate
  • surfactants such as polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil 60; sodium citrate, ede Stabilizers such as sodium acid; pre
  • the eye ointment can be formulated using a commonly used base such as white petrolatum or liquid paraffin.
  • the intercalator can be formulated using biodegradable polymers such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, polyacrylic acid, etc., if necessary, excipients, binders, stable An agent, a pH adjuster, and the like can be appropriately selected and used as necessary.
  • biodegradable polymers such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, polyacrylic acid, etc., if necessary, excipients, binders, stable
  • An agent, a pH adjuster, and the like can be appropriately selected and used as necessary.
  • the intraocular implant preparation is prepared using a biodegradable polymer such as polylactic acid, polyglycolic acid, lactic acid / glycolic acid copolymer, lactic acid-caprolactone copolymer, polyanhydride, polyorthoester, polyepsilon caprolactone, etc. If necessary, excipients, binders, stabilizers, pH adjusters and the like can be appropriately selected and used as necessary. It can also be formulated using non-biodegradable polymers such as ethylene vinyl acetate copolymer, and if necessary, excipients, binders, stabilizers, etc. are appropriately selected as necessary. Can be used.
  • a biodegradable polymer such as polylactic acid, polyglycolic acid, lactic acid / glycolic acid copolymer, lactic acid-caprolactone copolymer, polyanhydride, polyorthoester, polyepsilon caprolactone, etc.
  • the dosage of the present compound can be appropriately selected depending on the dosage form, patient symptoms, age, body weight and the like.
  • 0.01 to 5000 mg, preferably 0.1 to 2500 mg, particularly preferably 0.5 to 1000 mg can be administered in 1 to several times per day.
  • 0.00001 to 2000 mg, preferably 0.0001 to 1500 mg, particularly preferably 0.001 to 500 mg can be administered in 1 to several times per day.
  • 0.00001 to 10% (w / v), preferably 0.0001 to 5% (w / v), particularly preferably 0.001 to 1% is applied once to several times a day. can do.
  • one containing 0.0001 to 2000 mg can be applied.
  • an insertion agent or a preparation for intraocular implant one containing 0.0001 to 2000 mg can be inserted or implanted.
  • this compound significantly suppressed the decrease in the number of cells in the retinal nerve cell layer in the oral administration test in the NMDA-induced rat retinal disorder model. Moreover, in the intravitreal administration test in the same model, the decrease in the expression level of the neurofilament light chain in the retina was recovered.
  • the present compound is useful as an agent for preventing or treating optic neuropathy, an inhibitor of retinal neuronal cell death, or a recovery agent for the expression level of neurofilament light chain, and more particularly a prophylactic or therapeutic agent for glaucomatous optic neuropathy.
  • it is useful as a preventive or therapeutic agent for glaucomatous eye diseases such as glaucoma, glaucomatous visual field stenosis, glaucomatous optic nerve atrophy, glaucomatous optic neuropathy and the like.
  • Rat (Method for producing NMDA-induced rat retinal injury model) Rat [Slc: SD, male, about 7 weeks old] 100% (V / V) oxygen 0.5 L / min and 100% (V / V) nitrous oxide 1.5 L / min mixed gas 2 L / min Gas or air vaporized with 3% (V / V) halothane Inhalation of 3-4% (V / V) isoflurane gas at 1 to 1.5 L / min and general anesthesia, 1% ( Maintenance anesthesia was performed under conditions of (V / V) halocene or 2-3% (V / V) isoflurane.
  • NMDA manufactured by Sigma, [catalog number: M3262]
  • DMSO-containing PBS 10% (V / V) dimethyl sulfoxide-containing phosphate buffer
  • Rats 7 days after intravitreal administration of the NMDA solution were intraperitoneally administered with a 100 mg / kg pentobarbital sodium injection solution, and the eyes were removed.
  • the fixed eyeball was embedded in paraffin, and then sliced to prepare a retinal section (3 ⁇ m thickness), which was stained with hematoxylin-eosin. Eight retinal sections were prepared at 45 ⁇ m intervals so that the optic papilla could enter each eye.
  • NMDA intravitreal administration + base oral administration group NMDA solution 5 ⁇ L (10 nmol as NMDA) dissolved in PBS containing 10% (V / V) DMSO was administered into the vitreous body.
  • a 1% (W / V) aqueous solution of methylcellulose was orally administered once a day at a dose of 10 mL / kg for 7 days from the NMDA intravitreal administration date to 6 days later.
  • a 1% (W / V) aqueous solution of methylcellulose was orally administered 30 to 60 minutes before intravitreal administration of NMDA.
  • NMDA intravitreal administration + test compound oral administration group NMDA solution 5 ⁇ L (10 nmol as NMDA) dissolved in PBS containing 10% (V / V) DMSO was administered into the vitreous body.
  • the test compound suspended in 1% (W / V) methylcellulose solution was administered at a dose of 10 mg / kg for 7 days from the day of intravitreal administration of NMDA for 7 days at a dose of 10 mL / kg per day.
  • Oral administration was repeated twice.
  • a test compound suspended in a 1% (W / V) methylcellulose solution was orally administered at a dose of 10 mg / kg 30 to 60 minutes before NMDA administration.
  • Test results As an example of the test compound, the test results when 3 ′, 5-di-2-propenyl- (1,1′-biphenyl) -2,4′-diol (hereinafter also referred to as “honokiol”) was used. Table 1 shows. As is apparent from Table 1, honokiol significantly suppressed the decrease in the number of cells in the ganglion cell layer in the retina, which occurred in the NMDA-induced rat retinal injury model.
  • the present compound containing honokiol has the effect of preventing or treating optic neuropathy and the effect of suppressing retinal nerve cell death in systemic exposure dosage forms such as oral administration. In particular, it has the effect of preventing or treating glaucomatous optic neuropathy.
  • NMDA-induced rat retinal injury model quantitative polymerase chain reaction (hereinafter also referred to as PCR) evaluation by intravitreal administration of test compound)
  • evaluation method by quantitative PCR the amount of expression in the retinal tissue of a neurofilament light chain (hereinafter also referred to as “NFL”), which is a main component of the optic nerve axon and important for maintaining the shape of the axon, As an index, the effectiveness of the test compound was evaluated.
  • PCR quantitative polymerase chain reaction
  • QuantTect Multiplex PCR Master Mix synthesized cDNA, NFL primer / probe according to the instructions attached to QuantTect Multiplex PCR Kit (1000) (manufactured by QIAGEN, [Cat. No. 204545]) (manufactured by Sigma [custom made])
  • a primer probe of glyceraldehyde 3-phosphate dehydrogenase hereinafter also referred to as “GAPDH” (AppliedBiosystems, [Catalog No .: 4352338E]
  • AppliedBiosystems [Cat #: 7500- 03]
  • the expression level of NFL was calculated by correcting the expression level of NFL with the expression level of GAPDH, which is a housekeeping gene, according to Equation 1. Thereafter, according to Formula 2, the group administered with 10% (V / V) DMSO-containing PBS intravitreal was set to 100%, and the group administered with 10 nmol NMDA intravitreal was set to 0%. NFL recovery rate (%) was calculated. The number of cases in each group is 2 to 3 (4 to 6 eyes).
  • the NFL primer / probe sequences used in the present invention are as follows.
  • NMDA intravitreal administration group NMDA solution 5 ⁇ L (10 nmol as NMDA) dissolved in PBS containing 10% (V / V) DMSO was administered into the vitreous body.
  • Table 3 shows test results when honokiol and its structural isomer, magnolol (which is basically known to have the same action as honokiol), are used as an example of the test compound.
  • honokiol restores the decrease in the expression level of NFL that occurs in the NMDA-induced rat retinal injury model
  • honokiol a structural isomer of honokiol
  • the present compound containing honokiol has a prophylactic or therapeutic effect on optic neuropathy even in the form of local administration, and also has a recovery effect on the expression level of NFL.
  • a tablet of the above formulation can be coated with 3 mg of a coating agent (for example, a coating agent such as hydroxypropylmethylcellulose, macrogol, talc, titanium oxide, silicone resin) to obtain the intended tablet.
  • a coating agent for example, a coating agent such as hydroxypropylmethylcellulose, macrogol, talc, titanium oxide, silicone resin
  • a desired tablet can also be obtained by changing suitably the kind and / or quantity of this compound and an additive.
  • Aqueous injection (in 100 ml) 100 mg of this compound Sodium chloride 750mg Macrogol 400 1000mg Sodium hydroxide Appropriate amount Hydrochloric acid Appropriate amount Sterilized purified water Appropriate amount A desired aqueous injection can be obtained by appropriately changing the type and / or amount of the present compound and additives.
  • the present compound is useful as a preventive or therapeutic agent for optic neuropathy, an inhibitor of retinal neuronal cell death, or a recovery agent for the expression level of neurofilament light chain, and in particular, a prophylactic or therapeutic agent for glaucomatous optic neuropathy, more specifically It is useful as a prophylactic or therapeutic agent for glaucomatous eye diseases such as glaucoma, glaucomatous visual field stenosis, glaucomatous optic nerve atrophy, glaucomatous optic neuropathy.

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Abstract

La présente invention concerne un composé qui est utile en tant qu'agent prophylactique ou thérapeutique pour les troubles du nerf optique, en tant qu'inhibiteur de l'apoptose des cellules du ganglion rétinien ou en tant qu'agent de récupération du niveau d'expression d'une chaîne légère des neurofilaments, notamment un composé qui peut présenter l'activité physiologique susmentionnée lorsqu'il est administré par voie orale. La présente invention concerne spécifiquement le 3'-5-di-2-propényl-(1,1'-biphényl)-2,4'-diol, un ester de celui-ci, ou un sel du composé ou de l'ester. Le composé, l'ester ou le sel peuvent remarquablement empêcher le nombre de cellules dans une couche cellulaire du ganglion rétinien de diminuer, dans un modèle de rat porteur d'un trouble rétinien induit par le NMDA, lorsqu'ils sont administrés par voie orale au modèle de rat et peuvent permettre la récupération de la réduction du niveau d'expression d'une chaîne légère des neurofilaments dans une rétine dans le modèle de rat lorsqu'ils sont administrés par voie intravitréenne au modèle de rat. Par conséquent, le composé, l'ester ou le sel sont utiles en tant qu'agent prophylactique ou thérapeutique pour les troubles du nerf optique, en tant qu'inhibiteur de l'apoptose des cellules du ganglion rétinien ou en tant qu'agent de récupération du niveau d'expression d'une chaîne légère des neurofilaments.
PCT/JP2009/054122 2008-03-05 2009-03-05 Agent prophylactique ou thérapeutique pour les troubles du nerf optique, qui comprend du 3',5-di-2-propényl-(1,1'-biphényl)-2,4'-diol en tant que principe actif Ceased WO2009110526A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117752640A (zh) * 2023-12-15 2024-03-26 中山大学中山眼科中心 和厚朴酚及其脂质体复合物在制备修复眼部神经或上皮损伤的药物中的应用

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10849918B2 (en) 2015-07-13 2020-12-01 Tohoku Techno Arch Co., Ltd. Composition for optic nerve protection

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 537, 2006, pages 64 - 69 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117752640A (zh) * 2023-12-15 2024-03-26 中山大学中山眼科中心 和厚朴酚及其脂质体复合物在制备修复眼部神经或上皮损伤的药物中的应用

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